Document classification is one of the most critical steps in the document analysis pipeline. There are two types of approaches for document classification, known as image-based and multimodal approaches. The image-based document classification approaches are solely based on the inherent visual cues of the document images. In contrast, the multimodal approach co-learns the visual and textual features, and it has proved to be more effective. Nonetheless, these approaches require a huge amount of data. This paper presents a novel approach for document classification that works with a small amount of data and outperforms other approaches. The proposed approach incorporates a hierarchical attention network(HAN) for the textual stream and the EfficientNet-B0 for the image stream. The hierarchical attention network in the textual stream uses the dynamic word embedding through fine-tuned BERT. HAN incorporates both the word level and sentence level features. While the earlier approaches rely on training on a large corpus (RVL-CDIP), we show that our approach works with a small amount of data (Tobacco-3482). To this end, we trained the neural network at Tobacco-3428 from scratch. Thereby, we outperform state-of-the-art by obtaining an accuracy of 90.3%. This results in a relative error reduction rate of 7.9%.

For the past several decades, abdominal prenatal ultrasonography has been the most significant technology in obstetrics with a long-established application. However, the frequency, exposure time, thermal and cavitation exposure indices, and increased acoustic output of the ultrasonic waves may be harmful to the embryo/fetus and might increase susceptibility to Autism Spectrum Disorder (ASD). The increase in the prevalence of ASD is associated with an affluent ethnicity, high socioeconomic status, and high parental education where prenatal ultrasonography is readily available and affordable. Enhanced biophysical adverse effects may link the analogous increase in prenatal ultrasonography and autism, and prenatal ultrasonography may emerge as a risk factor for autism. Radiography usage provides historical evidence for this fact: the predominant past opinion was that exposure to X-rays during pregnancy caused no significant risk to a fetus. However, the association between X-ray exposure and childhood leukemia was only established 40 years after X-ray use began. This review focuses on excessive PUS usage and ASD development. Public Abstract Advancements in medical technology over the past several decades have made prenatal ultrasound more frequently accessible to expecting mothers during their pregnancy, especially for the affluent. A parallel development in health care is the increase in autism diagnoses (Autism Spectrum Disorder, or ASD) in children of affluent families. There is a general lack of studies of the impact of prenatal ultrasound on fetuses, especially around varying attributes such as frequency, duration of exposure, and thermal and cavitation indices. There is also a historical precedent set, where exposing fetuses to X-rays was not found to be harmful until it was linked to the development of childhood leukemia decades later. This paper seeks to establish a need to further study these attributes of prenatal ultrasound overuse and their possible impact on a developing fetus, with a special focus on the occurrence of Autism.

(1) Background: tuberculosis (TB) is considered one of the leading causes of death by a single in-fectious agent worldwide. This study aimed to identify hotspots of people diagnosed with tu-berculosis and abusive use of alcohol, tobacco and other drugs in communities through a geo-spatial intelligence application; (2) Methods: ecological study with a spatio-temporal approach. We considered tuberculosis cases diagnosed and registered in the Notifiable Diseases Information System, which presented information on alcoholism, smoking, and other drugs. Spatial Variations in Temporal Trends (SVTT) and scan statistics were applied for the identification of Hotspots; (3) Results: of 29.499 cases of tuberculosis were identified. And when we applied the STTT for al-coholism, three Hotspots were detected, one of which was protective (RR: 0.08 – CI95%: 0.02 – 0.32) and two at risk (RR:1.42 – CI95%: 1.11 – 1.73; RR: 1.39 - CI95%: 1.28 – 1.50). Regarding smoking, two risk clusters were identified (RR: 1.15 - CI95%: 1.01 – 1.30; RR: 1.68 - CI95%: 1.54 – 1.83). For other drugs, a risk cluster was found (RR: 1.13 - CI95%: 0.99 – 1.29) and two protections (RR: 0.70 - CI95%: 0.63 – 0.77; RR: 0.76 – CI95%: 0.65 – 0.89); (4) Conclusions: it was evidenced in the communities a problem of TB and drug addiction. Use disorder perhaps in a person's brain and behavior and leads to an inability to continue their treatment, putting the community at risk for TB.

Publicly-funded scientists have a responsibility to engage with the public on scientific information, but are lacking a standardized framework and assessment strategy to do it well. The PEPS (Public Engagement Practices for Scientists) Method is an outcomes-centered framework employing standardized pedagogical methods with quantifiable outcomes. This approach reveals that scientists often have unrealistic expectations for achieving affective learning outcomes (i.e. changing views from anti- to pro-vaccine) by solely cognitive learning strategies (i.e. supplying data). The PEPS Method can serve as a roadmap for standardized science communication assessments, complementing existing science communication training programs for the next generation of scientists.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

1) Background: Bipolar or manic-depressive disorder is a malign mental disease that frequently faces social stigma. Educational and thinking models are needed to increase people’s awareness and understanding of the disorder. The arts have potential to achieve this goal. 2) Methods: This paper builds on the recent use of heavy metal music as a thinking and education model. It emphasizes the artistic component of heavy metal and its potential to characterize the symptomatology during the episodes of (hypo)mania and depression and the recurrence of these episodes. Heavy metal music has diversified into subgenres that become allegorical to both the symptoms of episodes and the recurrence of bipolar cycles. 3) Results: Examples of songs are given that mirror distinct facets of the disorder. 4) Conclusion: Although the links drawn between art (music) and science (psychiatry) are inherently subjective, such connections might be used to trigger a learning process, facilitate judgment and decision-making, and induce affective reactions and memory formation in the listener. The approach may facilitate collaborative efforts and serve healthcare professionals and educators as a communication tool to aid the public’s comprehension of the disease and an associated social paradox: On one hand, bipolar disorder incurs substantial costs to society. On the other hand, it benefits from the creative artistic and scientific endeavors of bipolar individuals from which cultural and political gains may ensue.

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

The ratio of males to females with ASD is generally quoted as 4:1 though it is believed that there are biases preventing females being diagnosed and that the true ratio is lower. These biases have not been clearly identified or quantified. Starting with a clinical dataset of 1711 children <18 years old four different methods were employed in an inductive study to identify and quantify the biases and calculate the proportion of females missed. A mathematical model was constructed to compare the findings with current published data. The true male to female ratio appears to be 3:4. Eighty per cent of females remain undiagnosed at age 18 which has serious consequences for the mental health of young women.

Anomaly detection and segmentation aim at distinguishing abnormal images from normal images and further localizing the anomalous regions. Feature reconstruction based method has become one of the mainstream methods for this task. This kind of method has two assumptions: (1) The features extracted by neural network is a good representation of the image. (2) The autoencoder solely trained on the features of normal images cannot reconstruct the features of anomalous regions well. But these two assumptions are hard to meet. In this paper, we propose a new anomaly segmentation method based on feature reconstruction. Our approach mainly consists of two parts: (1) We use a pretrained vision transformer (ViT) to extract the features of the input image. (2) We design a self-attention autoencoder to reconstruct the features. We regard that the self-attention operation which has a global receptive field is beneficial to the methods based on feature reconstruction both in feature extraction and reconstruction. The experiments show that our method outperforms the state-of-the-art approaches for anomaly segmentation on the MVTec dataset. It is both effective and time-efficient.

The etiopathogenesis of autism spectrum disorder (ASD) remains largely unclear. Among other biological hypotheses, researchers have evidenced an imbalance in the endocannabinoid (eCB) system, which regulates some functions typically impaired in ASD, such as emotional responses and social interaction. Also, cannabidiol (CBD), the non-intoxicating component of Cannabis sativa, has been recently approved for treatment-resistant epilepsy. Seizures represent frequent medical comorbidities of ASD and could be responsible for the onset or worsening of behavioral problems. Thus, it has been hypothesized that cannabinoids could be useful in improving some ASD symptoms. Our systematic review was conducted according to the PRISMA guidelines and aimed to summarize the literature regarding the use of cannabinoids in ASD. After searching in Web of Knowledge^TM, PsycINFO, and Embase, we included ten studies (eight papers and two abstracts). Four ongoing trials were retrieved in ClinicalTrials.gov. Findings are promising, as cannabinoids appeared to improve problem behaviors, sleep, hyperactivity, and communication deficits, with limited cardiac and metabolic side effects. Interestingly, they generally allowed to reduce the number of prescribed medications and decreased the frequency of seizures in epileptic patients. Mechanisms of action could be linked to the excitatory/inhibitory imbalance found in people with ASD. However, further trials need to be implemented with better characterization and homogenization of samples, and well-defined outcomes.

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

Understanding brain function is one of the most important problems in human history. At present, there is no concrete theory for how the brain works. Here, a theory is presented that provides a detailed mechanistic biological account of the brain's capacities, including motor control, functional states, language, and thinking. Brain function is managed by a well-defined response (R) process that is generally similar to the process underlying the immune system. The R process is strongly reflected in the brain's anatomy, physiology, and external interactions. Different R process stages are supported by distinct excitatory networks located in different cortical layers, hippocampal fields, and bagal ganglia paths, by distinct coordination networks comprised of GABAergic interneurons, and by distinct molecular agents. The roles of norepinephrine, serotonin, dopamine and acetylcholine is to promote the alert, planning, goal-setting and execution R process modes, respectively. Opioids and oxytocin promote termination by success, failure, fight or run, while glucocorticoids and cannabinoids suppress acute responses to protect cells. The R process has two instances occurring at different time scales. The millisecond-scale Quax process implements the execution of hierarchical sequences of movements and thoughts, in which the selection of the next action is determined via interaction between top-down predictions and sensory inputs. The slower Need process controls the satisfaction of internal and external needs. The theory differs from the existing standard accounts in many of the major topics (e.g., the basal ganglia, dopamine, language), and shows how cognition results from biological processes.

In the paper the verification of forecasts of precipitation conditions measured by the standardized precipitation index SPI is presented. For the verification of categorical forecasts a contingency table was used. Standard verification measures were used for the SPI value forecast. The 30 day SPI moved every 10 days by 10 days was calculated in 2013-2015 from April to September on the basis of precipitation data from 35 meteorological stations in Poland. Predictions of the 30 day SPI were created in which precipitation was forecasted in the next 10 days (the SPI 10-day forecast) and 20 days (the SPI 20-day forecast). Both for the 10 and 20 days, the forecasts were skewed towards drier categories at the expense of wet categories. There was a good agreement between observed and 10-day forecast categories of precipitation. Less agreement is obtained for 20-day forecasts – these forecasts evidently “over-dry” the assessment of precipitation anomalies. The 10-day SPI value forecast accuracy is acceptable, whereas for the 20-day forecast is unsatisfactory. Both for the SPI categorical and the SPI value forecast, the 10-day SPI forecast is reliable and the 20-day forecast should be accepted with reservation and used with caution.

POH (Peri Orbital Hyperpigmentation) represents a minor clinical entity that attracts immense aesthetic damages and it generates social integration difficulties. This review focuses on the etiopathogenic causes of this entity, differentiating and reclassifying this defect as having, on the one hand, genetic causes of melanic hyperproduction – for Fitzpatrick cutaneous phototypes IV and V – and, on the other hand, both genetic and acquired vascular causes, in individuals with light-coloured skin phototypes. Hence, there is a big difference in the field of pathogenic treatment, for the two entities. In addition, this study notes the direct relationship between skin aging and POH, especially for aquired vascular causes. In this reasoning, other aesthetic deficiencies of the skin in the palpebral area should be also considered, like: blepharochalasis, wrinkles, the anatomical causes of the lower eyelid shading, symmetrical or asymmetric suborbital oedema. All of these issues will complicate the therapeutic decision and subsidiary, the pharmaceutical advice. In this context, the review shows the guidelines for a honest councelling of the patients, pointing the efficiency limit for the topical pharmaceutical medication (depigmentants, exfoliants) versus the necessity of minimally invasive or/ and surgical treatments (in blefarochalasis).

Triple X syndrome (TXS, also known as trisomy X or 47,XXX) has been associated with impaired overall neurocognitive functioning in children and relatively young adults. However, neurocognitive functioning in adults with TXS is poorly understood. The aim of this study was, therefore, to examine cognitive functioning in adults with TXS. Methods: In this cross-sectional study, data were collected from 34 adult women with TXS (mean age = 32.9; SD = 13.1) and 31 controls (mean age = 34.9; SD = 13.7). General intellectual functioning, semantic/verbal memory, visual/episodic memory, psychomotor speed, and attention and executive functioning were then compared between these two groups. Results: We found that general intellectual functioning was significantly lower in the TXS group compared to the control group. In addition, women with TXS had more attention problems and lower psychomotor speed, particularly motor processing speed. When the analyses were adjusted for IQ, the strength of these associations decreased. The women in the TXS group also scored significantly lower at free recall in the verbal memory test, but not in immediate or delayed recognition. Finally, visual/episodic memory and executive functioning did not differ significantly between groups. Conclusions: Our analysis revealed that women with TXS score lower in general intellectual functioning and have impairments in motor processing speed and attention compared to controls, but do not differ with respect to executive functioning. These results offer new insights for improving the support of adults with TXS both at school and in the workplace.

Objective: The aim of the current study was to examine whether and to what extent mood disorders, comprising major depression and bipolar disorder, are accompanied by structural changes in the brain as measured using voxel-based morphometry (VBM). Methods: We have performed a VBM study using a 3Т MRI system (GE Discovery 750w) in patients with mood disorders (n=50), namely 39 with major depression and 11 with bipolar disorder, compared to 42 age, sex and education matched healthy controls. Results: Our results show that depression was associated with significant decreases in grey matter (GM) volume restricted to regions located in medial frontal and anterior cingulate cortex on the left side and middle frontal gyrus, medial orbital gyrus, inferior frontal gyrus (triangular and orbital parts), and middle temporal gyrus (extending to the superior temporal gyrus) on the right side. When the patient group was separated into bipolar disorder and major depression the reductions remained significant only for the patients with major depressive disorder. Conclusions: Using VBM the present study was able to replicate decreases in GM volume restricted to frontal and temporal regions in patients with mood disorders mainly major depression, as compared with healthy controls.

Studies into the cognitive effects of alcohol have been mixed. They also present methodological challenges, often relying on self-report of alcohol consumption leading to hangover. The current study used BAC (obtained via breathalyser) and self-reported drinking behavior during a night out and related these to hangover severity and cognitive function measured over the internet in the same subjects the following morning. Volunteers were breathalysed and interviewed as they left a central entertainment district of an Australian state capital. They were provided with a unique identifier and, the following morning, logged on to a website. This included an online version of the Alcohol Hangover Severity Scale (AHSS), and number and type of drinks consumed the previous night and the eTMT-B - a validated, online analogue of the Trail Making Test B of executive function and working memory. Hangover severity was significantly correlated with one measure only, namely the previous night’s BAC (r = .228, p = .019). Completion time on the eTMT-B was significantly correlated with hangover severity ( r = .245, p = .012), previous night’s BAC (r = .197, p = .041) and time spent dinking (r = .376, p < .001). These findings confirm that alcohol hangover negatively affects cognitive functioning and that poorer working memory and executive performance correlates with hangover severity. The results also support the utility of using online measures in hangover research.

Transdermal alcohol biosensors have the ability to detect the alcohol that emanates from the bloodstream and diffuses through the skin. However, they have suffered from long-term fouling of the sensor element and drift in the resulting sensor readings over time. Here, we report a disposable cartridge platform that solves the problem of sensor fouling, and an enzymatic detection pathway that minimizes baseline drift for sensitive detection. Laboratory characterization of the enzymatic alcohol sensor demonstrates a linear sensor range of between 0 and 50 mM. Further, we show continuous transdermal alcohol data recorded with a human subject over 48 hours.

Autism spectrum disorder (ASD) refers to the diverse range of neurodevelopmental disorders accompanying impairments in social interaction, difficulties in communication, and stereotyped or repetitive behaviors. Unlike the older term, autism, the newer term, ASD, better reflects the broad range of autistic symptoms and denotes a single diagnostic category of autism accompanied by numerous conditions. The pineal hormone melatonin is a well-known neuroprotectant and circadian entrainer. This hormone crosses the placenta and enters the fetal circulation, then conveys photoperiodic information to the fetus during pregnancy. These actions enable normal sleep patterns and circadian rhythms, followed by normal neurodevelopment. Melatonin also reduces oxidative stress, which is harmful to the central nervous system. Therefore, melatonin acts as a neuroprotectant and circadian entrainer, and may reduce the risk of neurodevelopmental disorders such as ASD.

No studies have examined the immune fingerprint of major neuro-cognitive psychosis (MNP) or deficit schizophrenia using M1 macrophage cytokines in combination with chemokines such as CCL-2 and CCL-11. The present study delineated the neuro-immune fingerprint of MNP/deficit schizophrenia by analyzing plasma levels of IL-1β, sIL-1RA, TNF-α, sTNFR1, sTNFR2, CCL-2 and CCL-11 in MNP (n=120) versus healthy controls (n=54) in association with neurocognitive deficits (as assessed with the Brief Assessment of Cognition in Schizophrenia) and PHEMN (psychotic, hostility, excitation, mannerism and negative) symptoms. All immune biomarkers were significantly higher in MNP than in normal controls. MNP was best predicted by a combination of CCL-11, TNF-α, IL-1β and sIL-1RA which yielded a bootstrapped (n=2000) area under the Receiver Operating Curve of 0.985. Composite scores reflecting M1 macrophage activity and neurotoxic potential including combined effects of CCL-11 plus CCL-2 were significantly increased in MNP. Nevertheless, the effects of increased IL-1β and TNF-α in MNP were attenuated (statistically) by increased sIL-1RA and sTNFR2, two negative immune-regulatory markers. A large part of the variance in PHEM (38.4%-52.6%) and negative (65.8-7439%) symptoms was explained by combinations of immune markers whereby CCL-11 was consistently the most important. The immune markers also explained a large part of the variance in the Mini Mental State examination, list learning, digit sequencing task, category instances, controlled word association, symbol coding and Tower of London. Soft Independent Modeling of Class Analogy performed on the biomarkers showed that the inter-class distance between the models constructed around MNP and controls was 19.3 indicating a good separation. Partial Least Squares analysis showed that 72.7% of the variance in overall phenomenology was explained by the regression on IL-1β, sIL-1RA, CCL-11, TNF-α (all positively) and education (inversely). It is concluded that the combination of the above-mentioned markers defines MNP as a distinct neuro-immune disorder and that those markers in combination explain a large part of the variance in memory and executivive impairments and PHEMN symptoms.

The Gilles de la Tourette syndrome (GTS) and Non-Coeliac Gluten Sensitivity (NCGS) may be associated. We analyse the efficacy of a gluten-free diet (GFD) in 29 patients with GTS (23 children; 6 adults) in a prospective pilot study. All of them followed a GFD for one year. The YGTSS, Y-BOCS/CY-BOCS and GTS-QOL questionnaires were compared before and after the GFD. 74% of children and 50% of adults were males, not significant (NS). At the beginning of the study, 69% of children and 100% of adults had associated OCD (NS). At baseline, the YGTSS scores were 55.0 ± 17.5 (children) and 55.8 ± 19.8 (adults) (NS), the Y-BOCS/CY-BOCS scores were 15.3 (SD = 12.3) (children) and 26.8 (9.2) (adults) (p = 0.043), and the GTS-QOL scores were 42.8 ± 18.5 (children) and 64 ± 7.9 (adults) (p = 0.000). NCGS was frequent in both groups, with headaches reported by 47.0% of children and 83.6% of adults (p = 0.001). After one year on a GFD there was a marked reduction in measures of tics (YGTSS) (p = 0.001), and the intensity and frequency of OCD (Y-BOCS/CY-BOCS) (p = 0.001), along with improved QOL (p = 0.001) in children and adults. In conclusion, a GFD maintained for one year in GTS patients led to a marked reduction in tics and OCD both in children and adults.

As on 31.03.2020, 55.4 % (205135 MW) of total installed capacity (370106 MW) in India is through coal and lignite based power plants. These plants, set up by central, state and private utilities with substantial capital investment are facing consistently reducing Plant Utilization Factor (known as Plant Load Factor, PLF, in India). In the year 2019-20 the national average thermal power PLF stood at 55.4%, down from 78.6 % in 2007-08. On the other hand, the electricity demand is consistently rising in the country and there exists a peak and energy shortage at national level. In 2019-20 energy shortage was 0.7 % and peak shortage was 0.5 %. A disturbing paradox therefore exists here. On one hand, the country is power deficit, and on the other hand, a large amount of coal based affordable power, ready to be generated by thermal power generators, remains grossly unused. Looking into the fact that considerable investment has gone into developing these thermal power generation assets in the country, the falling PLF is a matter of concern for all the key stakeholders including the power producers, lenders, regulators and consumers. This paper identifies seven major factors that are affecting PLF of thermal power plants and then makes an attempt to project future scenario of PLF so that critical stakeholders can intervene through appropriate actions. Primary research with responses from power professionals has been used to find out the major factors. Future projection of PLF has been done using Partial Least Square (PLS) regression. Projection shows that in the Business As Usual case (Factors increasing at the current CAGR rate), the thermal power plants will face very low level of PLF (14.76 %) by 2024-25. This will mean that many plants will be shut down and many will run for only few hours in a day that too at very low loads. If the future generation mix is kept as indicated by Central Electricity Authority (CEA), a Govt. of India in its report (Draft report on optimal generation capacity mix for 2029-30- CEA- Govt of India) then the thermal power plant average PLF can sustain above 68 % until 2024-25. If followed, this path can be a breather for the thermal power plants.

A probabilistic description is essential for understanding the dynamics of stochastic systems far from equilibrium, given uncertainty inherent in the systems. To compare different Probability Density Functions (PDFs), it is extremely useful to quantify the difference among different PDFs by assigning an appropriate metric to probability such that the distance increases with the difference between the two PDFs. This metric structure then provides a key link between stochastic systems and information geometry. For a non-equilibrium process, we define an infinitesimal distance at any time by comparing two PDFs at times infinitesimally apart and sum these distances in time. The total distance along the trajectory of the system quantifies the total number of different states that the system undergoes in time, and is called the information length. By using this concept, we investigate the information geometry of non-equilibrium processes involved in disorder-order transitions between the critical and subcritical states in a bistable system. Specifically, we compute time-dependent PDFs, information length, the rate of change in information length, entropy change and Fisher information in disorder-to-order and order-to-disorder transitions, and discuss similarities and disparities between the two transitions. In particular, we show that the total information length in order-to-disorder transition is much larger than that in disorder-to-order transition, and elucidate the link to the drastically different evolution of entropy in both transitions. We also provide the comparison of the results with those in the case of the transition between the subcritical and supercritical states and discuss implications for fitness.

Sleep disorders (SD) have a complex aetiology, and socioeconomic status (SES) as determined by social class, household income, ethnicity and education plays an important role in their development. As SD are associated with cognitive impairment and mood disorders, they in turn impact SES. Socioeconomic status also influences allostatic load caused by chronic accumulation of stress throughout life. Environmental and psychological stressors have a direct effect on SD, and they are modulated by SES, in combination with comorbidities like obesity and cardiovascular disease. This review explores the recent theories about the influence of SES on the development of SD in the general population, whether or not occurring with comorbidities, and also focusses on the interplay between socioeconomic status, circadian rhythms, aging and clinical outcomes like metabolic diseases and cancer.

In 2011, it was reviewed that there is a strong co-occurrence between major depression and chronic fatigue syndrome (CFS), with fatigue and physio-somatic symptoms being key symptoms of depression, and depressive symptoms appearing during the course of CFS. Moreover, the comorbidity between both conditions may in part be explained by activated immune-inflammatory pathways, including increased translocation of Gram-negative bacteria and increased levels of pro-inflammatory cytokines, such as interleukin (IL)-1. Nevertheless, the possible involvement of activated microglia in this comorbidity has remained unclear. This paper aims to review microglial disturbances in major depression, CFS and their comorbidity. A comprehensive literature search was conducted using the PubMed / MEDLINE database to identify studies that are relevant to this current review. Depressed patients present neuroinflammatory alterations, probably related to microglial activation, while animal models show that a microglial response to immune challenges including lipopolysaccharides is accompanied by depressive-like behaviors. Recent evidence from preclinical studies indicate that activated microglia have a key role in the onset of fatigue. In chronic inflammatory conditions, such as infections and senescence, microglia orchestrate an inflammatory microenvironment thereby causing fatigue. In conclusion, based on our review we may posit that shared immune-inflammatory pathways and activated microglia underpin comorbid depression and CFS and that activated microglia are the main orchestrators of this comorbidity. As such, microglial activation and neuro-inflammation may be promising targets to treat the overlapping manifestations of both depression and CFS.

The study uses annual time series data from the South Africa Reverse Bank (SARB) from 1980 to 2020 to examine the effectiveness of fiscal policy on economic growth in South Africa. The Augmented Dickey-Fuller (ADF) and Phillips-Perron (PP) unit root tests, as well as the Johansen Co-integration test, Granger causality test, and Vector Auto-Regression (VAR) method, were used in the study. Real GDP per capita (RGDP) is used as proxy of economic growth and gross fixed capital formation (GFCF), government expenditure (GEXP) and government deficit (GOVD) as the proxies of fiscal policy. The ADF test results show that all variables are stationary at the first difference, with the exception of GFCF and GEXP, which are stationary at I(0), whereas the PP test results show that all variables are stationary at I(1), with the exception of GEXP, which is stationary at I(0). At Maximum Eigenvalue, the four variables are not cointegrated. The findings of the Granger causality test demonstrated a unidirectional causation from GOVD to RGDP, as well as a bidirectional causality from RGDP to GFCF and GEXP. Error Correction Model Estimated using VAR shows that GFCF, GEXP have positive effect on RGDP whereas GOVD has a negative effect on RGDP in the short run. The findings also presented that the VAR's residuals are homoscedastic, which means they are normally distributed and have no serial correlation.

Background: Extremely rare progressive diseases like Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) can be neonatally lethal and therefore go undiagnosed or are difficult to treat. Recent sequencing efforts have linked this disease to mutations in GPX4, with consequences in the resulting enzyme, glutathione peroxidase 4. This offers potential diagnostic and therapeutic avenues for those suffering from this disease, though the steps toward these treatments is often convoluted, expensive, and time-consuming. Main body: The CureGPX4 organization was developed to promote awareness of GPX4-related diseases like SSMD, as well as support research that could lead to essential therapeutics for patients. We provide an overview of the 21 published SSMD cases and have compiled additional sequencing data for four previously unpublished individuals to illustrate the genetic component of SSMD, and the role of sequencing data in diagnosis. We outline in detail the steps CureGPX4 has taken to reach milestones of team creation, disease understanding, drug repurposing, and design of future studies. Conclusion: The primary aim of this review is to provide a roadmap for therapy development for rare, ultra-rare, and difficult to diagnose diseases, as well as increase awareness of the genetic component of SSMD. This work will offer a better understanding of GPx4-related diseases, and help guide researchers, clinicians, and patients interested in other rare diseases find a path towards treatments.

We aimed to evaluate the feasibility and preliminary efficacy of trauma-focused group psychotherapy in adolescents who experienced traumatic events in Korea. Participants were assigned and recruited from two sites in Korea. Children in Disaster: Evaluation and Recovery (CIDER) V1.0 is a trauma-focused group psychotherapy approach consisting of psychoeducation, normalization, stabilization, and techniques of managing the traumatic memory. The CIDER intervention consists of eight 50-minute-long sessions. The effectiveness of the intervention was evaluated using the Korean version of the Children’s Response to Traumatic Events Scale-Revised (K-CRTES-R), the Beck Depression Inventory (BDI), the State Anxiety Inventory for Children (SAIC), and the Pediatric Quality of Life Inventory (PedQL). Data were analyzed by Wilcoxon signed-rank test. We recruited 22 traumatized adolescents (mean age 16 years; SD 1.43; range 13–18 years old; 71.4% boys) in this pilot study. The K-CRTES-R scores were significantly improved (Z = −2.85, p < 0.01). The BDI demonstrated the effectiveness of the therapy (Z = −2.35, p < 0.05). The assessment of the PedQL supported the effect of CIDER (Z = −3.08, p < 0.01). However, there was no statistically significant differences in the SAIC scores (Z = −1.90, p > 0.05). The results show that there is preliminary evidence that CIDER intervention reduces post-traumatic stress and depressive symptoms and improves quality of life. Our findings indicate that CIDER is feasible for treating adolescents exposed to traumatic events. Larger controlled trials are needed to establish the efficacy of this trauma-focused group psychotherapy and examine its impact on post-traumatic stress disorder.

Children and young people (CYP) with neurodevelopmental disorders (NDDs) may be particularly vulnerable to adverse mental health effects due to the COVID-19 pandemic. We conducted a cross-sectional U.K parent-reported study from 2nd April-2nd June 2020, using the Strengths & Difficulties Questionnaire. CYP with NDDs (n=371) compared to neurotypical controls, had a higher prevalence of emotional symptoms (42% vs 15%), conduct problems (28% vs 9%), and lower prosocial behaviours (54% vs 22%). Those with attention-deficit/hyperactivity disorder showed inflated conduct, and those with autism spectrum disorder exhibited decreased prosocial behaviours. Females with ASD had higher emotional symptoms compared to males.

In this paper, we propose an unsupervised blind restoration model for images in hybrid degradation scenes. The proposed model encodes the content information and degradation information of images and then uses the attention module to disentangle the two kinds of information. It can improve the ability of disentangled presentation learning for a generative adversarial network (GAN) to restore the images in hybrid degradation scenes, enhance the detailed features of restored image and remove the artifact combining the adversarial loss, cycle-consistency loss, and perception loss. The experimental results on the DIV2K dataset and medical images show that the proposed method outperforms existing unsupervised image restoration algorithms in terms of peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and subjective visual evaluation.

Contact with nature is suggested to be as an important resource for human health and well-being. Stress alleviation and reduction of mental fatigue are main instances of improvement of human health and well-being in contact with nature. Although the term restoration experience in contact with nature has been used repeatedly for concepts of stress alleviation and reduction of mental fatigue, these refer to different sets of theories and research studies. In this paper, by reviewing the nature-health related theories of Biophilia, Stress Recovery Theory, Attention Restoration Theory and Supportive Environment Theory (SET), the similarities and differences between these two concepts have been discussed. Moreover, the measurement approach instruments based on different study methodologies and aims are provided. This paper could provide information for future studies with focus on factors to be of benefit for restoration experience in design and planning of natural landscape environments with the aim of health and well-being development.

This review focuses on the evidence for neurotherapeutics for Attention Deficit Hyperactivity Disorder (ADHD). EEG-Neurofeedback has been tested for about 45 years with latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback of frontal activations in ADHD using functional magnetic resonance imaging or near-infrared spectroscopy, finding no superior effects over control conditions. Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements. Trigeminal nerve stimulation has shown to improve ADHD symptoms with medium effect in one RCT. Modern neurotherapeutics are attractive due to their relative safety and potential neuroplastic effects. However, they need to be thoroughly tested for clinical and cognitive efficacy across settings and beyond core symptoms and for their potential for individualised treatment.

Purpose: Obstructive sleep apnoea (OSA) affects patients’ quality of life and health. Magnesium (Mg) is an essential mineral and a potent antioxidant. Mg deficiency can worsen oxidative stress caused by sleep deprivation or disorders. The impact of OSA on serum Mg levels and its health consequences remain unclear. Methods: This study systematically reviewed clinical studies investigating the serum Mg levels of OSA patients and the potential relationships with other biomarkers.Results: Six articles were included for qualitative synthesis; five were used in quantitative analysis. Two out of four studies that compared OSA patients to healthy controls found them to have significantly lower serum Mg levels. Our meta-analysis with three studies shows that patients with OSA had significantly lower serum Mg with an effect size of -1.22 (95% CI: -2.24, -0.21). However, the mean serum Mg level of OSA patients (n=251) pooled from five studies (1.90 mg/dL, 95% CI: 1.77, 2.04) does not differ significantly from the normal range. OSA severity appears to affect serum Mg negatively. Serum Mg levels generally improve after treatment, coincide with the improvement of OSA severity. Low serum Mg levels correlate with worsening of cardiovascular risk biomarkers of C-reactive protein, ischaemia-modified albumin, and carotid intima-media thickness. The serum Mg levels also potentially correlate with biomarkers for lipid profile, glucose metabolism, calcium and heavy metals. Conclusions: Sleep deprivation appears to deplete Mg levels of OSA patients, making them at risk of Mg deficiency, which potentially increases systemic inflammation and the risk of cardiovascular and metabolic diseases.

Major Depression Disorder (MDD) is accompanied by an immune response characterized by increased levels of pro-inflammatory and immune-regulatory cytokines and cytokine-induced stimulation of indoleamine-2,3-dioxygenase (IDO). There is also some evidence that anti-inflammatory drugs may have a clinical efficacy in MDD.The aim of this study is to examine the clinical effects of an eight-week combinatorial treatment of ketoprofen (a nonsteroidal anti-inflammatory drug) combined or not with sertraline, on serum levels of IDO, interferon (IFN)-γ, interleukin (IL)-4 and transforming growth factor (TGF)-β1 in association with changes in the Beck-Depression Inventory-II (BDI-II). The study included 140 MDD patients and 40 normal controls. The pre-treatment serum levels of IDO, IFN-γ, TGF-β1 and IL-4 were significantly higher in MDD patients compared with the control group. Treatment with sertraline with or without ketoprofen significantly reduced the increased baseline production of all 4 biomarkers to levels which were similar as those of normal controls. Ketoprofen add-on had a significantly greater effect on IDO and BDI-II as compared with placebo. The reductions in IDO, IL-4 and TGF-β1 during treatment were significantly associated with those in the BDI-II.In conclusion, the clinical efficacy of both sertraline + ketoprofen may be ascribed at least in part to attenuated IDO levels and immune-inflammatory responses in MDD. Moreover, add-on treatment with ketoprofen may augment the efficacy of sertraline by attenuating IDO. However, these treatments may also significantly reduce the more beneficial properties of T helper-2 and T regulatory (Treg) immune subsets. Future research should develop immune treatments that target the immune-inflammatory response in MDD, while enhancing the compensatory immune-regulatory system (CIRS).

Since January, the disease caused by the Sars Cov-2 virus has spread and following pandemic. In a few months, the virus is seriously affecting the health systems of the various countries of the world and placing people in difficult psychological conditions. Few scientific resources on mental health have been published but still no one has proposed an action plan to cope the future psychological problems.This manuscript provides a plan to easily frame the priorities of mental health area related to COVID-19 to be taken into consideration which should be disseminated and that should be known by all health professionals and also by the major administrators of public health.

Targets detection in synthetic aperture radar (SAR) remote sensing images, which is a fundamental but challenging problem in the field of satellite image analysis, plays an important role for a wide range of applications and is receiving significant attention in recent years. Besides, the ability of human visual system to detect visual saliency is extraordinarily fast and reliable. However, computational modeling of SAR image scene still remains a challenge. This paper analyzes the defects and shortcomings of traditional visual models applied to SAR images. Then a visual attention model designed for SAR images is proposed. The model draws the basic framework of classical ITTI model; selects and extracts the texture features and other features that can describe the SAR image better. We proposes a new algorithm for computing the local texture saliency of the input image, then the model constructs the corresponding saliency maps of features; Next, a new mechanism of feature fusion is adopted to replace the linear additive mechanism of classical models to obtain the overall saliency map; Finally, the gray-scale characteristics of focus of attention (FOA) in saliency map of all features are taken into account, our model choose the best saliency representation, Through the multi-scale competition strategy, the filter and threshold segmentation of the saliency maps can be used to select the salient regions accurately, thereby completing this operation for the visual saliency detection in SAR images. In the paper, several types of satellite image data, such as TerraSAR-X (TS-X), Radarsat-2, are used to evaluate the performance of visual models. The results show that our model provides superior performance compared with classical visual models. By further contrasting with the classical visual models, Our model reduce the false alarm caused by speckle noise, and its detection speed is greatly improved, and it is increased by 25% to 45%.

It is not new in medical history to propose a global concern to be classified as a disease. Defining a concern into disease allows to assign ethical responsibilities to develop powerful and effective interventions. It also allow to appropriate distribute the resources uniformly economically and morally. In 2003, World Health Organization report stated that 30-50 % of patients do not take their medications as prescribed associated with morbidity, mortality and health cost. It was considered a global concern, however, irrespective of decades of researches conducted on medication adherence, we are still unable to state that medication adherence issues are being resolved. In this review, we have described few apprehensions in current understandings of medication adherence that have limited its research. We have also proposed medication adherence as disorder and provided its’ definition and classification

Background: India has one-fifth of the world's population and the number of people suffering from mental illness is assumed to be huge considering the contribution of mental disorders to the overall burden of the disease being 13.9 %. Objectives of Study: To estimate prevalence and patterns of mental illnesses to assess the current mental health services and systems in the Madhya Pradesh. Material and Methods: Multi-stage, stratified, random cluster sampling technique, with random selection based on probability proportionate to size at each stage. A total of 3240 individuals aged 18 years and above were interviewed. Both quantitative and qualitative methods were employed. A set of 10 instruments including Mini International Neuro-psychiatric Interview were utilized. Results: The overall weighted prevalence for any mental illness was 16.7% lifetime and 13.9% current. Treatment-gap for all mental health problems is as high as 91% in the state along with huge socioeconomic impact of mental illness. Conclusions: This huge burden of mental, behavioural and substance use disorders, in Madhya Pradesh, calls for immediate attention of political leaders, policy makers, health professionals, opinion-makers and society at large. It is hoped that the data from the study will inform mental health policy and legislation and help shape mental health care delivery systems in the country.

Background: Post-traumatic stress disorder (PTSD) is a common debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested for these patients. Deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. 2) Methods: We review the neurocircuitry and up to date clinical concepts that may be of relevance for the implementation of DBS in posttraumatic stress disorder (PTSD). 3) Results: The role of DBS in treatment-refractory PTSD patients has been investigated relying on both preclinical and clinical studies. 4) Conclusions: DBS for PTSD is in its preliminary phases and likely to provide hope to patients with medical refractory PTSD following the results of randomized controlled studies.

The voluminous daily output of autism research has become increasingly disconnected, existing largely within highly specific subspecialty areas, and lacking cross-disciplinary linkages of context, theory, and findings to inform a unified body of knowledge. Robust syntheses of published research across the fields of psychiatry, cellular and molecular biology, neurology, endocrinology, immunology, behavioral and social sciences, and pedagogy may help clarify and extend current knowledge by guiding more efficient future research efforts investigating underlying causes, developmental divergences, novel treatments, and specific, sensitive biological markers in autism. This synthesis of interdisciplinary research indicates the hypothalamic-pituitary-adrenal (HPA) stress axis may be at the center of an interaction among sex steroids, immune function, signaling protein transcriptions, neurogenesis, and dysregulation of brain structures sending or receiving projections from the HPA stress axis. These interaction manifest observably as a range of sexually dimorphic behaviors and functional limitations often falling within the current diagnostic features of Autism Spectrum Disorder (ASD). The pathogenicity of endocrine dysregulation may serve as a valuable model for developing a cohesive theory of ASD by explaining how the HPA and connected brain areas respond to extreme conditions of dysregulated endocrine signaling to cause symptoms associated with autism.

Poor understanding of malnutrition burden is a common reason for not prioritizing the care of small and nutritionally at-risk infants aged under-six months (infants u6m). We aimed to estimate the anthropometric deficit prevalence in infants u6m attending health centres, using the Composite Index of Anthropometric Failure (CIAF); and to assess the overlap of different individual indicators. We undertook a two-week survey of all infants u6m visiting each of 18 health centres in two zones of the Oromia region, Ethiopia. We measured weight, length, and MUAC (Mid upper arm circumference); and calculated weight-for-length (WLZ), length-for-age (LAZ), and weight-for-age z-scores (WAZ). Overall, 21.7% (95% CI: 19.2; 24.3) of infants u6m presented CIAF and of these, 10.7% (95% CI: 8.93; 12.7) had multiple anthropometric deficits. Low MUAC overlapped with 47.5% (95% CI: 38.0; 57.3), 43.8% (95% CI: 34.9; 53.1), and 42.6% (95% CI: 36.3; 49.2) of the stunted, wasted and CIAF prevalence, respectively. Underweight overlapped with 63.4% (95% CI: 53.6; 72.2), 52.7% (95% CI: 43.4; 61.7), and 59.6% (95% CI: 53.1; 65.9) of the stunted, wasted and CIAF prevalence, respectively. Anthropometric deficits, single and multiple, are prevalent in infants attending health centres. WAZ overlaps more with other forms of anthropometric deficits than MUAC.

Visual question answering (VQA) is receiving increasing attention from researchers in both the computer vision and natural language processing fields. There are two key components in the VQA task: feature extraction and multi-modal fusion. For feature extraction, we introduce a novel co-attention scheme by combining Sentence-guide Word Attention (SWA) and Question-guide Image Attention (QIA) in a unified framework. To be specific, the textual attention SWA relies on the semantics of the whole question sentence to calculate contributions of different question words for text representation. For the multi-modal fusion, we propose a “Cross-modal Multistep Fusion (CMF)” network to generate multistep features and achieve multiple interactions for two modalities, rather than focusing on modeling complex interactions between two modals like most current feature fusion methods. To avoid the linear increase of the computational cost, we share the parameters for each step in the CMF. Extensive experiments demonstrate that the proposed method can achieve competitive or better performance than the state-of-the-art.

Water deficit caused by drought is a significant threat to crop growth and production. Nitric oxide (NO), a water- and lipid-soluble free radical, plays an important role in cytoprotection. Apart from a few studies supporting the role of NO in drought responses, little is known about this pivotal molecular amendment in the regulation of abiotic stress signaling. In this review, we highlight the knowledge gaps in NO roles under drought stress and the technical challenges underlying NO detection and measurements, and we provide recommendations regarding potential avenues for future investigation. The modulation of NO production to alleviate abiotic stress disturbances in higher plants highlights the potential of genetic manipulation to influence NO metabolism as a tool with which plant fitness can be improved under adverse growth conditions.

Background: Social Anxiety Disorder (SAD) is among the most common anxiety disorders worldwide with data largely emerging from the Euro-American and Pacific Rim populations. In contrast, there is a dearth of studies among the populations of Arabian Gulf countries including Oman. This study has two interrelated aims: (i) to explore the prevalence of SAD among Omani adults, and (ii) to tease out the links between sociodemographic factors and SAD in Oman. Methods: A cross-sectional study via an online survey was conducted among 1019 adult Omani nationals residing in Oman. The presence of SAD was assessed using the Arabic version of the Liebowitz Social Anxiety Scale (LSAS). Result: Nearly half the participants (45.9%, n=468) endorsed themselves as having features of SAD as defined by LSAS. In the multivariate logistic analysis, participants below 40 years of age were 1.6 times (OR=1.568, p=0.026) more likely to have SAD than those who were 40 and older. Women were 1.3 times (OR=1.348, p=0.038) more likely to endorse SAD than men. Participants who had secondary or undergraduate education were respectively 1.5 times (OR=1.45, p=0.014) and 2.5 times (OR=2.509, p<.001) to have SAD than who were postgraduates. Conclusion: The present data suggest that 45.9% of the participants reached the cut-off for case-ness in LSAS, which is high compared to reports from other populations. As online survey respondents tend to belong to similar demographics, the current results need not be representative of the Omani adult population, which calls for studies that adopt more inclusive survey methods.

Background: Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology. Methods: In this case-control study, Thai women and men, aged 18-65 years, were divided in DS (n=40) and NDS (n=40) and were compared to controls (n=40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and IgA levels responses directed to Gram-negative bacteria were measured. Results: DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers. Conclusions: The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing towards greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI). We analyzed caspase-3 mediated apoptosis by TUNEL staining and PARP and annexin V western blotting. We correlated the neurodegeneration with sensorimotor deficits by conducting the animal behavioral tests including grid walk, balance beam, inverted screen test, and climb test. Our study demonstrated that the excess cell death or neurodegeneration correlated with the neuronal dysfunction and sensorimotor impairments associated with TBI.

1) Background: Keloids occur after the failure during the wound-healing process, persist the inflammation and are refractory to various treatments. The pathogenesis of keloids is still unclear. We previously analyzed the gene expression profiles in keloid tissue using microarray and Northern blot analysis and found that HtrA1 was markedly upregulated in the keloid lesions. HtrA1 is a member of the HtrA family of serine protease, has been suggested to play a role in the pathogenesis of various diseases including age-related macular degeneration and osteoarthritis by modulating proteins in extracellular matrix or cell surface. We focused on HtrA1, analyzed the localization and the role in keloid pathogenesis. 2) Methods: Twenty seven keloid patients and seven unrelated patients were enrolled in this study. We performed in situ hybridization analysis, immunohistochemical analysis, western blot analysis and cell proliferation assay. 3) Results: First, the fibroblast-like cells expressed HtrA1 higher in the active keloid lesions than in the surrounding lesions in situ hybridization. Second, the proportion of HtrA1-positive cells in keloid was higher than that of in normal skin significantly in immunohistochemical analysis. Third, HtrA1 protein was up-regulated, relative to normal skin tissue samples in western blot analysis. Finally, silencing of HtrA1 gene expression suppressed the cell proliferation significantly. 4) Conclusion: HtrA1 was highly expressed in keloid tissues and the suppression of HtrA1 gene inhibited the proliferation of keloid-derived fibroblasts. HtrA1 may promote keloid development through accelerating cell proliferation and remodeling keloid-specific extracellular matrix or cell surface molecules. HtrA1 is suggested to have an important role in keloid pathogenesis.

There is a long-standing association between exceptional cognitive abilities, of various sorts, and neuropsychiatric illness, but it has historically largely been investigated in an exploratory and non-systematic way. One group in which this association has been investigated with more rigor is in subjects who have been identified as twice exceptional; an educational term describing subjects who are both gifted and diagnosed with a neuropsychiatric disability. This term covers multiple conditions, but is of specific interest in particular in the study of autism spectrum disorder. Recent findings have led to the development of a hypothesis that a certain degree of the neurobiology associated with autism might even be advantageous for individuals and could lead to high giftedness, while becoming disadvantageous, once a certain threshold is surpassed. In this model, the same neurobiological mechanisms confer an increasing advantage up to a certain threshold, but become pathological past that point. Twice-exceptional individuals would be exactly at the inflection point, being highly gifted, but also symptomatic at the same time. Here, we review how existing neuroimaging literature on autism spectrum disorder can inform research on twice exceptionality specifically. We propose to study key neural networks with a robust implication in ASD to identify the neurobiology underlying twice-exceptionality. A better understanding of the neural mechanisms of twice exceptionality should help to better understand resilience and vulnerability to neurodevelopmental disorders and tofurther support affected individuals.

The devastating impact of the ongoing coronavirus disease 2019 (COVID-19) on public health, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has made fighting of the COVID-19 pandemic is a top priority in medical research and pharmaceutical development. Surveillance of SARS-CoV-2 mutations is essential for the comprehension of SARS-CoV-2 variant diversity and their impact on virulence and pathogenicity. The SARS-CoV-2 open reading frame 10 (ORF10) protein interacts with multiple human proteins CUL2, ELOB, ELOC, MAP7D1, PPT1, RBX1, THTPA, TIMM8B, and ZYG11B expressed in the lung tissues. Mutations and co-mutations in the emerging SARS-CoV-2 ORF10 variants are expected to impact the severity of the virus and its associated consequences. In this article, We highlight 128 single mutations and 35 co-mutations in the unique SARS-CoV-2 ORF10 variants in this article. The possible predicted effects of these mutations and co-mutations on the secondary structure of ORF10 variants and host protein interactomes are presented. The findings highlight the possible effects of mutations and co-mutations on the emerging 140 ORF10 unique variants from secondary structure and intrinsic protein disorder perspectives.

The latest research cumulates staggering information about the correlation between the microbiota-gut-brain axis and neurodevelopmental disorders. This review aims to shed light on the potential influence of the microbiome on the development of the most prevalent neurodevelopmental disease, attention-deficit-hyperactive disorder (ADHD). As the etiology and pathophysiology of ADHD are still unclear, finding viable biomarkers and effective treatment still represent a challenge. Therefore, we focused on factors that have been associated with a higher risk of developing ADHD while simultaneously influencing the microbial composition. We reviewed the effect of a differing microbial composition on neurotransmitter concentrations important in the pathophysiology of ADHD. Additionally, we deduced factors that correlate with a high prevalence of ADHD while simultaneously affecting the gut microbiome such as emergency c-sections, and premature birth as the former leads to a decrease of the gut microbial diversity and the latter causes neuroprotective Lactobacillus levels to be reduced. Also, we assessed nutritional influences such as breastfeeding, ingestion of short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs) on the host’s microbiome and development of ADHD. Finally, we discussed the potential significance of Bifidobacterium as a biomarker for ADHD, the importance of preventing premature birth as prophylaxis and nutrition as a prospective therapeutic measurement against ADHD.

Music and language are hypothesized to share neural resources, particularly at the level of syntax processing. Recent reports suggest that attention modulates this sharing of neural resources, but the time-course of the effects of attention, and the degree to which attention operates similarly on music and language, are yet unclear. In this EEG study we manipulate the syntactic structure of simultaneously presented musical chord progressions and garden-path sentences in a modified rapid serial visual presentation paradigm, while varying top-down attentional demands to the two modalities. The Early Right Anterior Negativity (ERAN) was observed in response to both attended and unattended musical syntax violations. In contrast, an N400 was only observed in response to attended linguistic syntax violations, and a P3 only in response to attended musical syntax violations. Results show that top-down allocation of attention indeed affects the processing of syntax in both music and language, with different neural resources acting upon the two modalities particularly at later stages of cognitive processing. However, the processing of musical syntax at an earlier stage of the perceptual-cognitive pathway, as indexed by the ERAN, is partially automatic, and is strongly indicative of separate neural resources for music and language.

The question of molecular similarity is core in cheminformatics, and is usually assessed via a pairwise comparison based on vectors of properties or molecular fingerprints. We recently exploited variational autoencoders to embed 6M molecules in a chemical space, such that their (Euclidean) distance within the latent space so formed could be assessed within the framework of the entire molecular set. However, the standard objective function used did not seek to manipulate the latent space so as to cluster the molecules based on any perceived similarity. Using a set of some 160,000 molecules of biological relevance, we here bring together three modern elements of deep learning to create a novel and disentangled latent space, viz transformers, contrastive learning, and an embedded autoencoder. The effective dimensionality of the latent space was varied such that clear separation of individual types of molecules could be observed within individual dimensions of the latent space. The capacity of the network was such that many dimensions were not populated at all. As before, we assessed the utility of the representation by comparing clozapine with its near neighbours, and did the same for various antibiotics related to flucloxacillin. Transformers, especially when as here coupled with contrastive learning, effectively provide one-shot learning, and lead to a successful and disentangled representation of molecular latent spaces that at once uses the entire training set in their construction while allowing ‘similar’ molecules to cluster together in an effective and interpretable way.

Borderline Personality Disorder (BPD) is a severe personality disorder whose neural bases are still unclear. Indeed, previous studies reported inconsistent findings concerning alterations in cortical and subcortical areas. In the present study we applied for the first time an unsupervised machine learning approach known as mCCA+jICA, in combination with a supervised machine learning approach known as Random Forest, to possibly find covarying GM-WM circuits that separate BPD from controls and that are also predictive of this diagnosis. To this aim, we analyzed the structural images of patients with BPD and matched HCs. Results showed that two GM-WM covarying circuits, including basal ganglia, amygdala, and portions of the temporal lobes and of the orbitofrontal cortex, correctly classified BPD against HC. Notably, these circuits are affected by specific child traumatic experiences (emotional and physical neglect, and physical abuse) and predict symptoms severity in the interpersonal and impulsivity domains. These results support that BPD is characterized by anomalies in GM and WM circuits related to early traumatic experiences and specific symptoms.

Virtual reality (VR) technology gains theoretical support from rehabilitation and pedagogical theories and offers a variety of capabilities in educational and interventional contexts with affordable products. VR is attracting increasing attention in the medical and healthcare industry as it provides fully interactive three-dimensional simulations of real-world settings and social situations, which are particularly suitable for cognitive and performance training including social and interaction skills. The worldwide rising trend in the prevalence of autism spectrum disorder calls for innovative and efficacious techniques for assessment and treatment. The article offers a summary of current perspectives and evidence-based applications of VR technology as an educational and intervention tool for individuals with autism spectrum disorder, with a primary focus on social communication including social functioning, emotion recognition, and speech and language. Technology- and design-related limitations as well as the disputes over the application of virtual reality to autism research and therapy are discussed and future directions of this emerging field are highlighted with regards to application expansion and improvement, technology enhancement, and the development of brain-based research and theoretical models.

In order to summarized the polygenic background of psychiatric diseases, polygenic risk scores (PRS) have been developed. Recently, PRS have been use to predict patients with higher comorbidities in psychiatric diseases, like dual diagnosis. PRS are principally derived in analysis of Caucasian and Asian populations, we are not aware of how this PRS could be applied in populations with high admixture. In order to explored this, the present work has the aim to analyzed if previous calculated PRS for psychiatric diseases could predict dual diagnosis in Mexican population, and also, if PRS calculation could be influenced by Mexican Amerindian (MA) global ancestry. We performed PRS calculation, using PRSice, with summary genome-wide association statistics previously published for psychiatric diseases, and also, performed Nagelkerke correlation test in order to established if PRS are correlated with dual diagnosis. We found that dual diagnosis could be predicted by major depressive disorder polygenic risk score. Nevertheless, schizophrenia polygenic risk score is highly correlated with global MA ancestry, independently of the schizophrenia diagnosis. Our results reinforced the notion that PRS calculation could be deviated by the MA global ancestry, nevertheless analysis on larger sample sizes are required in order to clarified this issue.

Yogic and meditative traditions have long held that the fluctuations of the breath and the mind are intimately related. While respiratory modulation of cortical activity and attentional switching are established, the extent to which electrophysiological markers of attention exhibit synchronization with respiration is unknown. To this end, we examined 1) frontal midline theta-beta ratio, an indicator of attentional control state known to correlate with mind wandering episodes and functional connectivity of the executive control network; 2) pupil diameter (PD), a known proxy measure of locus coeruleus (LC) noradrenergic activity; and 3) respiration for evidence of phase synchronization and information transfer (multivariate Granger causality) during quiet restful breathing. Our results indicate that both TBR and PD are simultaneously synchronized with the breath, suggesting an underlying oscillation of an attentionally relevant electrophysiological index that is phase-locked to the respiratory cycle which could have the potential to bias the attentional system into switching states. We highlight the LC’s pivotal role as a coupling mechanism between respiration and TBR, and elaborate on its dual functions as both a chemosensitive respiratory nucleus and a pacemaker of the attentional system. We further suggest that an appreciation of the dynamics of this weakly coupled oscillatory system could help deepen our understanding of the traditional claim of a relationship between breathing and attention.

It appears that up to 80% of females with autistic spectrum disorder (ASD) have not been diagnosed by 18 years of age. This translates to a prevalence of about 5-6%, and if true has serious implications for female mental health. One way of finding the true value is to use Bayes’ Theorem with a comorbid condition as a more easily recognizable flag. An obvious choice is anorexia nervosa (AN), but it transpires that the proportion of women with ASD who develop AN is unknown. This study uses published data in novel ways to provide two methods of estimating a range for this variable, and gives a median value of 8.3% for AN in ASD and with four other methods a median prevalence of 6% for female ASD. The clinical implications for diagnosis and management of ASD and comorbidities are discussed and a solution is provided for the rate of ASD in generalized joint hypermobility.

Previous evidence in support of a slowly acting (scale of 100s of seconds) and volume-transmitted component of cholinergic signaling was based largely on studies using measures of extracellular brain acetylcholine (ACh) levels which required several minutes to generate a single data point and typically employed AChEsterase inhibitors (AChEIs) to foster the measurement of ACh. Moreover, collecting such data points in correlation with relatively stable behavioral states has supported the view that extracellular ACh levels vary at a relatively slow rate. Here we argue that forebrain cholinergic signaling is exclusively phasic (milliseconds to perhaps seconds), unlikely to be volume-transmitted, and that previous neurochemical evidence and associated behavioral correlates may be re-interpreted in terms of integrated phasic cholinergic activity and specific behavioral and cognitive operations. The highly potent catalytic enzyme for ACh, AChE, limits the presence of an ambient extracellular ACh level and thus renders it unlikely that ACh influences target regions via relatively slow changes in extracellular ACh concentrations. Real-time amperometric recordings of cholinergic signaling have suggested a specific function of rapid, phasic or transient cholinergic signaling in attentional contexts. Optogenetic studies support a causal relationship between these transients on behavior. Combined electrochemical and neurophysiological recordings revealed that the powerful behavioral control by cholinergic transients involves the generation of high-frequency oscillations. Such oscillations are thought to recruit efferent circuitry to (re)activate dormant task sets. Evidence showing the impact of genetic variations of the capacity of cholinergic synapses likewise can be interpreted in terms of their impact on the ability to sustain generation of repeated phasic cholinergic signals, as opposed to effects on ambient ACh levels. Further, while notions of slowly-changing, sleep stage-associated variations in extracellular ACh levels and their functions are widely accepted, the evidence is in fact limited. An alternative hypothesis offers a role for high-frequency cholinergic transient signaling during REM sleep. By employing a theoretical framework that focuses on the phasic and causative characteristics and functions of cholinergic signaling, results from human cognitive neuroscience studies of cholinergic function may be substantially clarified and simplified. Compared to the current treatment of cholinergic deficits using AChEIs, the conceptualization of forebrain cholinergic signaling as wired, phasic, and causative predicts that drugs that either rescue transient presynaptic signaling or amplify or rescue the postsynaptic impact of phasic signals will be more efficacious in treating age- and dementia-related cognitive and cognitive-motor disorders.

Humans are incapable of judging the temporal order of visual events at brief temporal separations with perfect accuracy. Their performance---which is of much interest in visual cognition and attention research---can be measured with the temporal-order judgment task, which typically produces S-shaped psychometric functions. Occasionally, researchers reported plateaus within these functions, and some theories predict such deviation from the basic S shape. However, the centers of the psychometric functions result from the weakest performance at the most difficult presentations and therefore fluctuate strongly, leaving existence and exact shapes of plateaus unclear. This study set out to investigate whether plateaus disappear if the data accuracy is enhanced, or if we are ``stuck on a plateau'', or rather with it. For this purpose, highly accurate data were assessed by model-based analysis. The existence of plateaus is confidently confirmed and two plausible mechanisms derived from very different models are presented. Neither model, however, performs well in the presence of a strong attention manipulation, and model comparison remains unclear on the question which of the models describes the data best. Nevertheless, the present study includes the highest accuracy in visual TOJ data and the most explicit models of plateaus in TOJ studied so far.

Background: Mental synthesis is the conscious purposeful process of synthesizing a novel mental image from objects stored in memory. In our everyday use of language, we rely on mental synthesis to communicate an infinite number of images with a finite number of words. In typical children, the timeline of mental synthesis acquisition is highly correlated with an increasing vocabulary. Children with ASD, on the other hand, may learn hundreds of words but never acquire mental synthesis. In these individuals, tests assessing vocabulary comprehension may fail to demonstrate the profound deficit in mental synthesis and the resulting inability to understand flexible syntax and spatial prepositions. Objective: We developed a 20-question parent-reported evaluation tool designed to quantitatively assess mental synthesis ability and to serve as a complimentary scale for Autism Treatment Evaluation Checklist (ATEC). Results: Internal reliability was good (Cronbach’s alpha > .9), and the MSEC exhibited adequate test-retest reliability after a three- and nine-months follow up period. The MSEC results positively correlated with the ATEC communication subscale, providing support for construct validity. Moreover, MSEC scores were significantly different for children of different ASD severity levels confirming the known groups validity. Conclusions: This study represents the first step toward the development of an instrument to measure mental synthesis in children with ASD. Although the current empirical evaluation demonstrated strong evidence of excellent psychometric properties, such as validity and reliability, additional studies should be performed to replicate these findings.

(1) Background: Twitch.tv is a live video content website. As of 2022, Twitch users are generally adolescents and young adults, with estimates of the percentage of users aged 16-24 between 22.3% and 41%, predominantly males with estimates ranging from 65% to 78.36%. In recent years, “slotstream” content has become increasingly popular, where streamers gamble online while users watch them. (2) Methods: from July 2022 to November 2022, we researched articles related to Twitch, live streaming, gambling, casino, slot, gambling online, modeling, social media influencers, conditioning, and celebrities, searching for relevant studies in the databases LexisNexis Academic, Business Source Complete, PubMed, Web of Science, Freedom Collection, Health &amp; Medical Collection, Elsevier Journal, Springer, APA PsycARTICLES, Wiley, and other single journals. (3) Results: we took into consideration Gambling Disorder, Online Gambling Disorder, and Internet Gaming Disorder on the one hand, and consumer components such as persuasive communication and influencer-audience relationship on the other; we then hypothesized that the presence of these variables within the slotstream format is positively correlated with the development of pathological gambling, especially in an adolescent audience. (4) Conclusion: we assume that there is a positive correlation between watching slotstream content and the probability of developing both pathological and non-pathological gambling behavior.

A model that predicts levels of coronavirus (CoV) respiratory/fecal-oral transmission potentials based on the outer shell hardness has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Based mainly on the PID of N, SARS-CoV-2 is categorized as having intermediate levels of both respiratory and fecal oral transmission potential. Related to this, other studies have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and are characterized by case-fatality rates of 7.1% and 10.9%, respectively. The link between levels of respiratory transmission and virulence lies in viral load of body fluids and organ respectively. A virus can be infectious via respiratory modes only if the viral loads in saliva and mucus exceed certain minima. Likewise, a person may die, if the viral load is too high especially in viral organs. Inner shell proteins of viruses play important roles in the replication of viruses, and structural disorder enhances these roles by providing greater efficiency in protein-protein/DNA/RNA/lipid binding. This paper outlines a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.

To efficiently use its finite resources, the visual system selects for further processing only a subset of the rich sensory information. Visual masking and spatial attention control the information transfer from visual sensory-memory to visual short-term memory. There is still a debate whether these two processes operate independently or interact, with empirical evidence supporting both arguments. However, recent studies pointed out that earlier studies showing significant interactions between common-onset masking and attention suffered from ceiling and/or floor effects. Our review of previous studies reporting metacontrast-attention interactions revealed similar artifacts. Therefore, we investigated metacontrast-attention interactions by using an experimental paradigm in which ceiling/floor effects were avoided. We also examined whether metacontrast masking is differently influenced by endogenous and exogenous attention. We analyzed mean absolute-magnitude of response-errors and their statistical distribution. Our results support the hypothesis that metacontrast and endogenous/exogenous attention are largely independent with negligible likelihood for interactions. Moreover, statistical modeling of the distribution of response-errors suggests weak interactions modulating the probability of “guessing” behavior for some observers in both types of attention. Nevertheless, our data suggest that any joint effect of attention and metacontrast can be adequately explained by their independent and additive contributions.

The search for new materials that could improve the energy density of Li-ion batteries (LIB) is one of today’s most challenging issues. Recently, cation-disordered lithium-excess metal oxides have emerged as a promising new class of cathode materials for LIB, due to their high reversible capacities and nice structural stability. However, a full structural model of the Li-transition metal (TM) sharing sublattice and the origin of short range ordering (SRO) of cation ions requires further investigation. In this work, we put forward a Monte Carlo strategy of building a cation-disordered rocksalt material supercell model. The cation ions of Li_1.0Ti_0.5Ni_0.5O₂ (LTNO) are placed at the FCC sublattice sites with the constraint of Pauling’s electroneutrality rule, instead of a random way. This constraint causes the Li-Ti and Ni-Ni clustering (the cation short range ordering). Based on this model, we discussed the relationship between the short range ordering, the local distorting, the theoretic capacity and the order-disorder strengths. A unified understanding of these factors in cation-disordered materials may enable a better design of disordered-electrode materials with high capacity and high energy density.

Objective: Major depression (MDD) and a lifetime history of MDD are characterized by increased nitrosylation, while bipolar disorder type 1 (BP1), but not BP2, is accompanied by highly increased levels of oxidative stress and nitric oxide (NO) production. Nevertheless, it is unknown whether nitrosylation is involved in BP and whether there are differences in nitrosylation between BP1 and BP2.Methods: Serum IgM antibodies directed against nitroso (NO)-adducts were examined in MDD, BP1, BP2 and healthy controls, namely IgM responses to NO-cysteine, NO-tryptophan (NOW), NO-arginine and NO-albumin (SBA) in association with IgA/IgM responses to Gram-negative bacteria, IgG responses to oxidized low-density lipoprotein (oxLDL) and serum peroxides.Results: Serum IgM levels against NO adducts were significantly higher in BP1 and MDD as compared with healthy controls, whereas BP2 patients occupied an intermediate position. IgM responses to NO-albumin were significantly higher in BP1 and MDD than in BP2 patients. There were highly significant associations between the IgM responses to NO-adducts and IgG responses to oxLDL and IgA/IgM responses to Gram-negative bacteria.Conclusions: BP1 and MDD are characterized by an upregulation of the nitrosylome (the proteome of nitrosylated proteins), and increased IgM responses to nitrosylated conjugates. Increased nitrosylation may be driven by increased bacterial translocation and is associated with lipid peroxidation processes. Innate like (B1 and marginal zone) B cells and increased nitrosylation may play a key role in the major affective disorders through activation of immune-inflammatory and oxidative pathways, cardiovascular comorbidity and impairments in antioxidant defenses, neuro-glial interactions, synaptic plasticity, neuroprotection, neurogenesis, etc.

The movement toward prevention trials in people at-risk for Parkinson’s is rapidly becoming a reality. The authors of this article include a genetically at-risk advocate with the LRRK2 G2019S variant and two patients with rapid eye movement sleep behavior disorder (RBD), one of whom has now been diagnosed with Parkinson’s disease (PD). These authors participated as speakers, panelists, and moderators in the “Planning for Prevention of Parkinson’s: A Trial Design Forum” hosted by Massachusetts General Hospital in 2021 and 2022. Other authors include a young onset person with Parkinson’s (PwP) and retired family physician, an expert in patient engagement in Parkinson’s, and early career and veteran movement disorders clinician researchers. Several themes emerged from the at-risk participant voice concerning the importance of early intervention, the legitimacy of their input in decision-making, and the desire for transparent communication and feedback throughout the entire research study process. Challenges and opportunities in the current environment include lack of awareness among primary care physicians and general neurologists about PD risk, legal and psychological implications of risk disclosure, limited return of individual research study results, and undefined engagement and integration of individuals at-risk into the broader Parkinson’s community. Incorporating the perspectives of individuals at-risk as well as those living with PD at this early stage of prevention trial development is crucial to success.

Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common variants which differ across populations and hence do not fully account for HbF variation. To investigate rare and common variants influencing HbF levels in SCD, we performed targeted next generation sequencing covering exonic and other significant fetal hemoglobin-associated loci, including BCL11A, MYB, HOXA9, HBB, HBG1, HBG2, CHD4, KLF1, MBD3, ZBTB7A and PGLYRP1. Results revealed a range of functionally relevant genetic variants. Notably, there were significantly more deletions in individuals with high HbF levels (11% vs 0.9%). We identified frameshift deletion in individuals with high HbF levels and frameshift insertions in individuals with low HbF. CHD4 and MBD3 genes, interacting in the same sub-network, were identified to have a significant number of pathogenic or non-synonymous mutations in individuals with low HbF levels, suggesting an important role of epigenetic pathways in the regulation of HbF synthesis. This study provides new insights in selecting essential variants associated with extreme HbF levels in SCD.

Background: CCL11 (eotaxin) is a chemokine with an important role in allergic conditions. Recent evidence indicates that CCL11 plays a role in brain disorders as well. Aims: This paper reviews the associations between CCL11 and aging, neurodegenerative, neuroinflammatory and neuropsychiatric disorders.Methods: Electronic databases were searched for original articles examining CCL11 in neuropsychiatric disorders.Results: CCL11 is rapidly transported from the blood to the brain through the brain-blood barrier. Age-related increases in CCL11 are associated with cognitive impairments in executive functions, episodic and semantic memory and, therefore, this chemokine was described as an “endogenous cognition deteriorating chemokine” (ECDC) or “accelerated brain-aging chemokine” (ABAC). In schizophrenia, increased CCL11 is not only associated with impairments in cognitive functions, but also with key symptoms including formal thought disorders. Some patients with mood disorders and premenstrual syndrome show increased plasma CCL11 levels. In diseases of old age, CCL11 is associated with lowered neurogenesis and neurodegenerative processes and, as a consequence, increased CCL11 increases risk towards Alzheimer's Disease. Polymorphisms in the CCL11 gene are associated with stroke. Increased CCL11 also plays a role in neuroinflammatory disease including multiple sclerosis. In animal models, neutralization of CCL11 may protect against nigrostriatal neurodegeneration. Increased production of CCL11 may be attenuated by glucocorticoids, minocycline, resveratrol and anti-CCL11 antibodies.Conclusion: Increased CCL11 production during inflammatory conditions may play a role in human disease including age-related cognitive decline, schizophrenia, mood disorders and neurodegenerative disorders. Increased CCL11 production is a new drug target in the treatment and prevention of those disorders.

Context: Mental and menstrual health, two emerging aspects of health critical to the female population, are bidirectionally linked. But there is limited empirical evidence that establishes the association between these entities. This essay aims to draw the attention of researchers to this healthcare niche. Evidence Acquisition: A systematic review was carried out on literatures sourced from medical databases (e.g. PubMed, Google Scholar, Scopus, Science Direct, and Web of Science), and gray sources—popular and reputable institutional and journalistic websites that publishes mental or menstrual health research. The key words used for the search are “Menstruation, menstrual hygiene, menstrual disorders, premenstrual syndrome, period poverty, menarche, menopause, mental health, mental disorder, mental illness, depression, anxiety, phobia, mania, mood, and affect”. The initial search generated 368 results. But after the duplicates were removed, the exclusion criteria (publication before 2000) was applied, and manual review of abstract (for relevance) was done, 21 publications from the databases and 5 from gray sources were included in this essay. Results: Associations were found between menstrual cycle irregularities and disorders; and mental disorders such as premenstrual syndrome, premenstrual dysphoric disorder, major depressive disorder, major anxiety disorder, psychotic disorder, bipolar disorder, borderline personality disorder, sleep disorder, substance use/abuse, and suicidal ideation and attempts.Few positive associations between mental and menstrual health were recorded, and several research and treatment gaps were identified. Conclusion: Research into the links between mental and menstrual health should not remain a fringe area of scientific curiosity, as it shows tremendous promise in improving healthcare offered to women/girls globally.

In the remote sensing domain, it is crucial to complete semantic segmentation on the raster images, e.g., river, building, forest, etc, on raster images. A deep convolutional encoder--decoder (DCED) network is the state-of-the-art semantic segmentation method for remotely sensed images. However, the accuracy is still limited, since the network is not designed for remotely sensed images and the training data in this domain is deficient. In this paper, we aim to propose a novel CNN for semantic segmentation particularly for remote sensing corpora with three main contributions. First, we propose applying a recent CNN called a global convolutional network (GCN), since it can capture different resolutions by extracting multi-scale features from different stages of the network. Additionally, we further enhance the network by improving its backbone using larger numbers of layers, which is suitable for medium resolution remotely sensed images. Second, "channel attention'' is presented in our network in order to select the most discriminative filters (features). Third, "domain-specific transfer learning'' is introduced to alleviate the scarcity issue by utilizing other remotely sensed corpora with different resolutions as pre-trained data. The experiment was then conducted on two given datasets: (i) medium resolution data collected from Landsat-8 satellite and (ii) very high resolution data called the ISPRS Vaihingen Challenge Dataset. The results show that our networks outperformed DCED in terms of $F1$ for 17.48% and 2.49% on medium and very high resolution corpora, respectively.

Background: Healthcare attention is sometimes considered purely technical, but communication has proven to be closely related to clinical results and patient satisfaction. Therefore, evaluation of communication in the scope of healthcare is a priority. The purpose of this study was to validate and adapt, if necessary, the Spanish version of the Communication Styles Inventory (CSI) in a sample of nursing professionals. (2) Methods: The sample was made up of 2313 nursing professionals selected at random from various medical centers in Spain, and is therefore a sample actively employed at the time data were acquired. We started out from the Communication Style Inventory, a questionnaire for evaluating the predominance of certain individual communication behaviors on six scales (expressiveness, preciseness, verbal aggressiveness, questioningness, emotionality and impression manipulativeness). (3) Results: Confirmatory Factor Analysis of the model proposed showed god fit indices. The reliability of the model shown by the Cronbach’s alpha of α=.81 was adequate, and so was single-level and aggregate consistency. Finally, in the analysis of variance by type of contract, configural, metric and scalar invariance was acceptable, but not strict invariance. (4) Conclusions: This instrument progresses in measuring non-technical attributes, such as communication styles, in nursing personnel.

Electroencephalograms (EEGs) of children with reading disorder (RD) are characterized by higher power and coherence in slow frequencies (delta and theta bands) and lower power and coherence in the alpha band compared to EEGs of typically developed children. Neurofeedback (NFB) is useful for treating learning disorders by reinforcing the reduction of the theta/alpha ratio. This efficacy is supported by EEG power normalization and cognitive-behavioral improvement. To further explore brain changes in isolated areas, this study aimed to explore the effects of this NFB protocol on functional connectivity (coherence) in children with RD. Twenty children with RD and an abnormally high theta/alpha ratio underwent 30 sessions of NFB. After treatment, 90% of par-ticipants learned to decrease their theta/alpha ratio, and on average, children increased their reading accuracy and comprehension scores. Interhemispheric coherence diminished in the delta, theta and beta bands, mainly between frontopolar regions. Intrahemispheric coherence decreased in delta, theta and beta bands and increased in alpha band. The reduction in theta coherence be-tween the left frontal area and other regions of the left hemisphere had particular relevance for reading. These results suggest that this NFB treatment could positively impact reading-related functions in the brain networks of children with RD.

SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.

In this paper, we propose a novel approach to recognize radar targets on inverse synthetic aperture radar (ISAR) and synthetic aperture radar (SAR) images. This approach is based on the multiple salient keypoint descriptors (MSKD) and multitask sparse representation based classification (MSRC). Thus, to characterize the targets in the radar images, we combine the scale-invariant feature transform (SIFT) and the saliency map. The goal of this combination is to reduce the SIFT keypoints and their time computing time by maintaining only those located in the target area (salient region). Then, we compute the feature vectors of the resulting salient SIFT keypoints (MSKD). This methodology is applied for both training and test images. The MSKD of the training images leads to construct the dictionary of a sparse convex optimization problem. To achieve the recognition, we adopt the MSRC taking into consideration each vector in the MSKD as a task. This classifier solves the sparse representation problem for each task over the dictionary and determines the class of the radar image according to all sparse reconstruction errors (residuals). The effectiveness of the proposed approach method has been demonstrated by a set of extensive empirical results on ISAR and SAR images databases. The results show the ability of our method to predict adequately the aircraft and the ground targets.

Gender and identity issues permeate society as a whole. Therefore, the matters involving transgender individuals should be analised in order to understand the difficulties experienced by this population and the social practices implemented. In this sense, the objective of this study was to investigate the strategic themes and their evolution in relation to the theme. For this, a bibliometric performance and network analysis (BPNA) was carried out with the existing data in the Web of Science database between 1954 and march 2021. Twenty-three thousand and four hundred and seventy-one (23,471) articles were identified, which were included in the SciMAT software to perform a bibliometric analysis, resulting in the graph of the thematic evolution structure and the strategic diagram, in which 8 motor themes and a cross-cutting theme of great magnitude are highlighted, which are discussed in depth. The results show the relation between the transgender theme and gender, identity, sexual orientation, hormone therapy and gender-affirming surgery. It is concluded that, despite the large number of associated researches, some areas of study are still incipient, such as the inclusion of transgender people in the formal labor market and in the prison context, thus opening field for further studies.

The focus of this study was to investigate how individuals with bipolar disorder integrate auditory and visual speech information compared to non-disordered individuals and whether there were any differences in auditory and visual speech integration in the manic and depressive episodes in bipolar disorder patients. It was hypothesized that bipolar groups’ auditory-visual speech integration would be less robust than the control group. Further, it was predicted that those in the manic phase of bipolar disorder would integrate visual speech information more than their depressive phase counterparts. To examine these, the McGurk effect paradigm was used with typical auditory-visual speech (AV) as well as auditory-only (AO) speech perception on visual-only (VO) stimuli. Results. Results showed that the disordered and non-disordered groups did not differ on auditory-visual speech (AV) integration and auditory-only (AO) speech perception but on visual-only (VO) stimuli. The results are interpreted to pave the way for further research whereby both behavioural and physiological data are collected simultaneously. This will allow us understand the full dynamics of how, actually, the auditory and visual (relatively impoverished in bipolar disorder) speech information are integrated in people with bipolar disorder.

In recent years, researchers have paid increasing attention on hyperspectral image (HSI) classification using deep learning methods. To improve the accuracy and reduce the training samples, we propose a double-branch dual-attention mechanism network (DBDA) for HSI classification in this paper. Two branches are designed in DBDA to capture plenty of spectral and spatial features contained in HSI. Furthermore, a channel attention block and a spatial attention block are applied to these two branches respectively, which enables DBDA to refine and optimize the extracted feature maps. A series of experiments on four hyperspectral datasets show that the proposed framework has superior performance to the state-of-the-art algorithm, especially when the training samples are signally lacking.

Binge-eating disorder (BED) and bulimia nervosa (BN) have adverse psychological and medical consequences. Novel interventions, like the integration of virtual reality (VR) with cue-exposure therapy (VR-CET), enhance outcomes for refractory patients compared to cognitive behavior therapy (CBT). Little is known about the feasibility and acceptability of translating VR-CET into real-world settings. To investigate this question, adults previously treated for BED or BN with at least one objective or subjective binge episode/week were recruited from an outpatient University eating disorder clinic to receive up to eight weekly one-hour VR-CET sessions. Eleven of 16 (68.8%) eligible patients enrolled; nine (82%) completed treatment; 82% (9/11) provided follow-up data 7.1 (SD=2.12) months post-treatment. Overall, participant and therapist acceptability of VR-CET was high. Intent-to-treat objective binge episodes (OBEs) decreased significantly from 3.3 to 0.9/week (p &lt; .001). Post-treatment OBE 7-day abstinence rate for completers was 56%, with 22% abstinent for 28 days at follow-up. Among participants purging at baseline, episodes decreased from a mean of one to zero/week, with 100% abstinence maintained at follow-up. The adoption of VR-CET into real-world clinic settings appears feasible and acceptable, with a preliminary signal of efficacy. Findings, including some loss of treatment gains during follow-up may inform future treatment development.

Abstract Women victims of abuse can suffer neuropsychological sequelae that affect memory and attention, as well psychopathological disorders such as depression. These consequences affect their daily life and physical and psychological health. Objective: To analyze sequelae that affect attention and memory, as well a possible association of these sequelae to depression. Method: A total of 68 women victims of gender-based violence participated in the study. The participants were between 15 and 62 years of age and resided in Spain at the time of data collection. The Luria DNA Battery (Neuropsychological Diagnosis of Adults) by Manga and Ramos (2000); and the Beck Depression Inventory were applied. Results: Women victims of gender-based violence suffer neuropsychological sequelae, presenting low short-term memory and attentional control; and score low on the Luria-DNA battery. Of these women, 60% suffer from some relevant type of depression, and there are significant differences according to their degree of memory. Through the HJ-Biplot, a direct relationship was found between memory and attentional control with the total score of the Luria battery. On the other hand, an inverse relationship was found between short-term memory and depression. Lastly, three well-differentiated gender clusters of women victims of gender-based violence were identified. Conclusions: A lower rate of depression is observed in women victims of abuse when they have a more intact short-term memory.

Virtual reality (VR) describes a family of technologies which immerse users in sensorily-stimulating virtual environments. Such technologies have increasingly found applications in the treatment of neurological and mental health disorders. Depression, anxiety, and other mood abnormalities are of concern in the growing elderly population – especially those who reside in long-term care facilities (LTCFs). The transition from the familiar home environment to the foreign LTCF introduces a number of stressors that can precipitate depression. However, recent studies reveal that VR therapy (VRT) can promote positive emotionality and improve cognitive abilities in the elderly, both at home and in LTCFs. VR thus holds potential in allowing elderly individuals to gradually adapt to their new environments – thereby mitigating the detrimental effects of place attachment and social exclusion. Nevertheless, while the current psychological literature is promising, the implementation of VR in LTCFs faces many challenges. LTCF residents must gain trust in VR technologies, care providers require training to maximize the positive effects of VRT, and decision makers must evaluate both the opportunities and obstacles in adopting VR. Here, we concisely review the implications of depression related to place attachment in LTCFs, and explore the potential therapeutic applications of VR.

Apathy is a fundamental neuropsychiatric symptom of Korsakoff’s syndrome (KS) and has also been reported in patients with alcohol use disorder with no (AUD) or less severe cognitive disorders (ALC). However, research on the nature of apathy is limited in these groups. Aim of this study was to examine the multidimensional nature of apathy in patients with KS, ALC and AUD. Moreover, we examined differences between apathy ratings by patients and their professional caregivers, and related apathy to everyday functioning and overall cognition. Twenty-four patients with KS, 24 patients with ALC and 21 patients with AUD participated in this study. Apathy was measured using the Apathy Motivation Index (AMI), which distinguishes behavioral, emotional and social apathy. Both patients and professional caregivers reported social apathy as most prominent symptom, compared to behavioral and emotional apathy. Apathy ratings did not differ across the three patient groups. Discrepancies between patient and caregiver ratings were observed in patients with KS and ALC, with more severe apathy reported by caregivers. Caregiver-reported behavioral and social, but not emotional, apathy was related to everyday functioning. These results show that apathy is present in a substantial proportion of patients with alcohol addiction with or without cognitive impairments.

The COVID-19 pandemic affects not only physical health but also deteriorates mental health resulting in sleep problems, depression, and traumatic stress. Our research investigates the level of posttraumatic stress, perceived social support, opinions on positive and negative consequences of the pandemic, sense of security, and sense of meaning among nurses in the face of new and not fully understood global epidemiological phenomena. For this purpose, computer-assisted web interviewing methods were conducted between May 1 and May 15, 2020. Participating nurses completed the following research tools: The Impact Event Scale-Revised (IES-R), The Multidimensional Scale of Perceived Social Support (MSPSS), The Changes in Outlook Questionnaire (CIOQ), The Safety Experience Questionnaire (SEQ) and The Meaning in Life Questionnaire (MLQ). Three hundred and twenty-five nurses working throughout Poland joined the study of an average age of 39.18 ± 11.16 years. The average overall IES-R score in the study group was 1.78 ± 0.65. Among the dimensions of traumatic stress, the highest score was obtained in the dimension Avoidance 1.86 ± 0.73, then in the dimensions Hyperarousal 1.8 ± 0.78 and Intrusion 1.74 ± 0.83. Amongst studied nurses, the highest support rates were provided by significant others (22.58 ± 5.22), then from friends (21.91 ± 5) and family (21.45 ± 4.4). Among the surveyed nurses, higher average scores were noted in the subscale measuring positive psychological changes (18.56 ± 4.04). In contrast, a higher average level of assessment was noted on the Reflection on the safety dimension (4.21 ± 0.49). The mean MLQ score was 5.33 ± 0.87. A slightly higher result was observed in the subscale Presence (5.35 ± 1.14). The results of the research implemented during the period of severe psychological pressure associated with the COVID-19 pandemic provided information on symptoms of traumatic stress in the examined group of nurses. Their sense of security has been lowered and accompanied by an intensified reflection on issues concerning security. However, the sense of meaning (currently felt) in life remains higher than the tendency to searching for it. The surveyed nurses perceive individual support from the so-called significant others (apart from family and friends). They see positive changes resulting from painful experiences related to the COVID-19 pandemic, which can be characterized by adaptation in the form of posttraumatic growth.

Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric problem with a few core symptoms: weaknesses in social behavior, verbal impairments, repetitive behavior and restricted interests. Beyond the core symptoms, autism has strong association with other disorders such as intellectual disability, epilepsy, schizophrenia among many others. This paper outlines a theory of ASD with capacity to connect heterogeneous ‘core’ symptoms, medical and psychiatric comorbidities as well as other etiological theories of autism in a unifying cognitive framework rooted in neuroscience and genetics. Cognition is embedded into an ever-developing structure modified by experiences, including the outcomes of environment influencing behaviors. We introduce the hypothesis that autism is caused by deficits in component-based cognition and the internal learning reinforcing machinery. Specifically, we outline our Cartesian Factor forming autoencoder like model that supports cognition by breaking combinatorial explosion and discuss the cognitive and neural processes behind our model. The high dimensionality of sensory information poses serious problems, since the brain can handle only 7±2 relevant variables at a time making processes, such as the extraction and encoding of the relevant variables and their efficient manipulation critical. These processes are influenced by previous experiences and the internal reward system. In addition, large delays of distributed information processing should be counteracted by learned predictive models to synchronize sensory, proprioceptive, and cognitive signals and have timely and accurate model-based actions. Impairments in any of these aspects may disrupt learning and execution. Combinations of small impairments may allow the solving of low complexity tasks but may become visible if learned variables and the related metric are improper and imprecise, respectively, especially if their number is large. We claim that social interactions are amongst the most challenging cognitive tasks in terms of the number of variables involved. In turn, they are highly susceptible to combinations of small impairments. We consider impairments as the basic colors of autism, whereas the combinations of diverse impairments make the palette of autism. In turn, social processes can be spoiled in many ways and can lead to diverse comorbidities.

Panic disorder (PD) is characterized by recurrent and uncontrollable panic attacks associated with behavioral changes and/or persistent anxiety due to the attacks. The development of behavioral models in animals is important for the understanding of the psychobiological and behavioral bases of PD. The present article reviews the main models used in the current literature. Biobehavioral assays used in rats and mice include fear conditioning (which presents moderate predictive, face, and construct validities); the elevated T-maze (which presents good predictive validity, but low face and construct validities); electrical stimulation of the periaqueductal gray (which presents good face validity, but moderate construct validity); predator exposure models (which present good predictive and moderate construct validity); and hypercapnia-induced responses (which present moderate construct validity). These three approaches seek coherence with theories on fear as a way to increase its translational potential; thus, while the elevated T-maze is supported by the Deakin/Graeff theory, the mouse defense test battery relies on the concept of defensive distance, and periaqueductal gray stimulation is based on the functional neuroanatomy of fear. Moreover, to higher or lower degree the three models are supported by an “etho-experimental” approach, with careful observation of animal behavior as a way of discriminating different defensive strategies that model different aspects of anxiety, fear, and panic. These assays can be used, in conjunction with independent variables that attempt to simulate the vulnerabilities and stressors which lead to panic attacks, to produce true models of PD. Finally, an alternative/complementary model is proposed that uses zebrafish alarm reaction to study this disorder.

The prevalence of internet gaming disorders (IGD) is considerably high among youth, especially with social isolation imposed by the ongoing COVID-19 pandemic. IGD adversely affects mental health, quality of life, and academic performance. The Internet Gaming Disorder Scale (IGDS9-SF) is designed to detect IGD according to DSM-IV diagnostic criteria. However, inconsistent results are reported on its capacity to diagnose IGD evenly across different cultures. To ensure the suitability of the IGDS9-SF as a global measure of IGD, this study examined the psychometric properties of the IGDS9-SF in a sample of Sri Lankan university students (N = 322, mean age =17.2 ± 0.6, range = 16-18 years, 56.5% males) and evaluated its measurement invariance across samples from Sri Lanka, Turkey, Australia, and the USA. Among Sri Lankan students, a unidimensional structure expressed good fit, invariance across different groups (e.g., gender, ethnicity, and income), adequate criterion validity (strong correlation with motives of internet gaming, daily gaming duration, and sleep quality), and good reliability (alpha = 0.81). Males and online multiplayers expressed higher IGD levels, greater time spent gaming, and more endorsement of gaming motives (e.g., Social and Coping) than females and offline players. Across countries, the IGDS9-SF was invariant at the configural, metric, and scalar levels, albeit strict invariance was not maintained. The lowest and highest IGD levels were reported among Turkish and American respondents, respectively. In conclusion, the IGDS9-SF can be reliably used to measure IGD among Sri Lankan youth. Because the scale holds scalar invariance across countries, its scores can be used to compare IGD levels in the studied countries.

Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together. Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.

Healthy diet interventions have been shown to improve depressive symptoms, but there is a need for randomized controlled trials (RCTs) that are double-blind and investigate biological mechanisms. The primary objectives of this randomized controlled pilot trial were to test the palatability of the meals and acceptability of the intervention in preparation for a future 8-week RCT which will investigate whether a healthy Nordic diet improves depressive symptoms in individuals with major depressive disorder, and associated biological mechanisms. Depressed (n=10) and non-depressed (n=6) women and men were randomized to receive either a healthy Nordic diet (ND) or a control diet (CD) for 8 days. Participants were blinded to diet allocation and study hypotheses. Health questionnaires were completed before and after the intervention, and, throughout the study, questionnaires assessed ratings of liking and sensory properties of the meals, adherence, and open-ended feedback. In the ND group, 75% of participants consumed no non-study foods, compared to 50% of CD participants. The meals of both diets, on average, received good ratings for liking and sensory properties, though the ND ratings were somewhat higher. Overall, results were positive and informative, indicating that the planned RCT will be feasible and well-accepted, with some proposed modifications.

Background: The passage through university, as a complex experience, can heighten personal susceptibility to eating disorders. The objective of this research is to determine how gender, age, year of course, and center or faculty can influence the risk of an eating disorder among university students. Method: A transversal and descriptive study with a probabilistic sample of 516 Spanish students from 26 university degrees is performed, by administering the Inventory Eating Disorder-Reference criterion (EDI-3-RF) to the students. Results: It was found that the female students enrolled in second-year grades presented a greater obsession with thinness and body dissatisfaction, that the male students did more physical exercise to control their weight, and that those under 20 years and the students from both the Health and Law Faculties presented greater bulimic behavior. Conclusions: It is necessary to implement preventive measures adapted to the university students.

Teeth segmentation plays a pivotal role in dental diagnosis, treatment, planning, and the development of computer-aided dental systems. It enables precise identification and analysis of dental structures, aiding in detecting dental abnormalities, measuring tooth dimensions, and assessing oral health conditions. Accurate teeth segmentation also facilitates the automation of dental workflows, leading to improved efficiency and reduced human error. Artificial Intelligence (AI) has witnessed rapid advancements, with various approaches developed or enhanced. While Convolutional Neural Networks (CNNs) have been widely used in medical image segmentation, the U-Net architecture has emerged as a standout performer due to its exceptional segmentation capabilities. This paper presents a proof of concept for the Attention U-Net architecture, as previously used in [1], applied to teeth segmentation. The study demonstrates the superior performance of this network in accurately segmenting teeth using a newly available benchmark dataset called Tufts Dental X-Ray Dataset. When trained and tested on 10-fold cross-validation, the model achieved an average dice coefficient of 95.01%, intersection over union of 90.6%, and pixel accuracy of 98.82%. These scores surpass those of all other networks implemented on the same dataset. By leveraging the Attention U-Net architecture, our research showcases the potential of advanced AI techniques in dental radiography. The findings contribute to the ongoing efforts to develop automated systems to assist dental professionals in their clinical practice.

There is growing evidence on the relevance of self-efficacy for well-being and functioning among individuals with psychotic disorders, but specific self-efficacy for coping with stress has rarely been investigated. This study explored the outcomes of an intervention for the improvement of coping resources based on a training in coping skills and coping with stress self-efficacy (CSSE). Fourteen adult volunteers who were diagnosed with schizophrenia (n=12) or schizoaffective disorder (n=2) were matched in clinical and sociodemographic characteristics and randomly assigned to the study groups. The intervention group received the training along with their pharmacological therapy; the control group received their prescribed drug therapy. Participants completed self-reports on CSSE, perceived successful daily functioning based on coping skills, and clinical status (BPRS-E). Trained patients showed a significant increase in CSSE and reported greater successful functioning status, and significant improvements in their clinical status were also observed. All these enhancements remained at 3-month and 6-month follow-ups. Control participants showed no significant changes. Moreover, the intervention condition interacted with CSSE and perceived coping functioning in explaining improvements in clinical status: in the treatment group, greater CSSE translated into enhanced daily functioning, and this improvement predicted better clinical status. These findings stress the relevance of promoting coping resources in psychotic disorders and provide preliminary evidence for the potential benefits of CSSE.

The aim of this study was to examine the prevalence of self-reported and parent-reported bullying victimization, perpetration, and victimization-perpetration and the associations of autistic social impairment and attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms with bullying involvement in adolescents with high functioning autism spectrum disorder (ASD). A total of 219 adolescents with high functioning ASD participated in this study. The associations of sociodemographic characteristics, parent-reported autistic social impairment on the Chinese Social Responsiveness Scale, and parent-reported ADHD and ODD symptoms on the Short form of the Swanson, Nolan, and Pelham Version IV Scale (SNAP-IV)-Chinese version with self-reported and parent-reported bullying victimization, perpetration, and victimization-perpetration evaluated using the Chinese version of the School Bullying Experience Questionnaire were examined using logistic regression analysis. The agreement between self-reported and parent-reported bullying involvement was low. Compared with bullying involvement experiences reported by adolescents themselves, parents reported higher rates of pure bullying victimization (23.7% vs. 17.8%) and victimization-perpetration (28.8% vs. 9.1%) but a lower rate of pure bullying perpetration (5.9% vs. 9.1%). Deficit in socio-communication increases the risk of being pure victims and victim-perpetrators. Parent-reported victim-perpetrators had more severe ODD symptoms than did parent-reported pure victims. The agreement between self-reported and parent-reported bullying involvement of adolescents with high functioning ASD was low. Deficit in socio-communication and ODD symptoms were significantly associated with a high risk of bullying involvement in adolescents with high functioning ASD.

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases, and psychiatric disorders. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants, and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses, and chronic diseases. KYN, kynurenic acid, xanthurenic acid, and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2, 3-oxygenases, and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines, and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia, and autism spectrum disorder.

Nanoparticles offer available tools for MDD research. In this assay, we applied CBR1 (cannabinoid receptor 1) knockout (CB1-/-) mice to study whether functionalized solid lipid nanoparticles loading with curcumin and dexanabinol (Cur/SLNs-HU-211) exhibited anti-depressant outcomes through CBR1. Wild-type (CB1+/+) animals together with CBR1 knockout (CB1-/-) animals received daily injections of Corticosterone (CORT) for 3 weeks to obtain MDD mice model, and then the therapeutic action of Cur/SLNs-HU-211 were evaluated, respectively. Our work show that Cur/SLNs-HU-211 nanoparticles in the existence of CBR1 facilitate an efficient motor function improvement in CORT-induced MDD mice model. Cur/SLNs-HU-211 nanoparticles alleviated symptoms on CB1+/+ MDD mice and resulted in dopamine and norepinephrine recovery following CORT-induced neurotoxicity. In conclusion, the possible mechanisms underlying the antidepressant effect of Cur/SLNs-HU-211 might be the induction of CB1 expression and downstream RASGEF1C and Egr1 expression, together with a significantly upregulation of neuron-specific genes in CB1+/+ mice only. In conclusion, CBR1 is necessary during the process of antidepressant activities of Cur/SLNs-HU-211 nanoparticles. This study confirms that Cur/SLNs-HU-211 nanoparticles based CBR1 in vivo targeting would be a potentially feasible and safe way to motivate future therapeutic strategies of Major Depressive Disorder.

Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder.The aims of this study were to use clinical and biomarker data to construct statistically-derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology and biomarkers.In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers.Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the “recurrence LV”), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL and impairments in cognitive tests. All those factors could be combined into a reliable “ELT-staging LV” which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities and HR-QoL.Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage; a relapse-regression stage; and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

Culture exploits the acquisition of meaningful content by crafting regimes of shared attention, determining what is relevant, valuable, and salient. Culture changes the field of relevant social affordances worthy of being acted upon in a context-sensitive manner. When relevant affordances are highly weighted, their attentional capture and their salience increase the probability of them being enacted due to the associated expectation for minimizing prediction error. This process is known as active inference. In the digital era, individuals need to infer the action-related attributes of digital cues, here characterized as digital affordances. The digital affordances of digital social platforms are of particular interest here. Digital social affordances are defined as online possibilities of social interactions. By their own nature, these are salient because they are related to social interactions and relevant social cues. However, the problem of digital social platforms is that they are not equivalent to situated social interactions because their structure is built, mediated, and defined by third-parties with diverse interests. The third-parties behind the digital social platforms are using the same mechanism exploited by culture to manipulate the shared patterns of attention. Moreover, digital social platforms are deliberately designed to be hyper-stimulating, making digital social affordances highly rewarding and increasingly salient. This appropriation, for economic purposes, is an issue of great importance, especially as the COVID-19 pandemic brought deep global changes, pushing societies to an online digital way of life. Here, we examined different types of digital social affordances under an active inference view, placing them into two categories, those for self-identity formation, and those for belief-updating. This paper aims to analyze digital social affordances in light of the prediction error dynamics they might elicit to their users. Although each of the analyzed digital social affordances allows different epistemic and instrumental digital actions, they all share the characteristic of having an "easy" and a fast expected rate of error reduction. Here, we aim to provide a new hypothesis about how the design behind digital social affordances is built on our natural attractiveness to minimize prediction error and the resulting positive embodied feelings when doing so. Finally, it is suggested that because digital social affordances are becoming highly weighted in the field of affordances, this might be putting at risk our context-sensitive grip on a rich, dynamic and varied field of relevant affordances.

Anemia and thyroid disorders are global health issues that affect all ages but are more apparent in women. In this case, some serological components responsible for IDA and TSH disorders in women have been found actively regulated through a complex steroidal-calcitriol mediated pathway. This research has been investigated the correlation between Calcitriol and the serological components responsible for IDA and TSH disorders in childbearing and non-child-bearing women of different health conditions. Experimental sampling from 452 women suffering from both IDA and TSH disorders were taken, aged between 0 and 70 years. Serological parameters, such as iron, total iron-binding capacity and ferritin, were assessed for IDA profiling, whereas thyroid-stimulating hormone and free thyroxin were for TSH profiling based on the individual’s serum calcitriol status. The resulted serological data were interpreted using sophisticated computer programming language and algorithms for quantitative biochemical analysis. The study resulted in a significant correlation between FT4 and Calcitriol (P<0.0001) for all age groups. TSH also showed strong interactions with the fluctuation of calcitriol level (P<0.0001), except for the children aged below 10 years (P<0.063). The iron, TIBC, TSH, and FT4 showed phenomenal regulation with the steroidal-calcitriol concentration for congenital patients. Unlike the others, ferritin has a substantial connection with Calcitriol (P<0.0064) fluctuation in the serum. To ratify, the concentrations of TSH, FT4, iron, TIBC, and ferritin were found to be significantly interconnected in terms of serum calcitriol level in women suffering from IDA and TSH disorders simultaneously. To understand the accuracy and efficacy of the Calcitriol in IDA and TSH disorders, some other inflammatory markers and parathyroid hormone analysis are need in future studies, besides a large number of samples.

The Speer allergic tension-fatigue syndrome (SATFS) is a classic syndrome characterized by allergy-like symptoms, muscle tension, headache, chronic fatigue, and a particular behavior. The particular behavior displayed includes symptoms such as hyperkinesis, hyperesthesia (i.e., insomnia), restlessness, and distractibility, among others. Interestingly, these symptoms are very similar to recent descriptions of attention deficit hyperactivity disorder (ADHD), the most prevalent neurodevelopmental disorder worldwide, which is characterized by inattention, hyperactivity and impulsivity. Although the exact cause of ADHD remains unknown, it has been proposed that deficiency of the enzyme diamine oxidase (DAO), which metabolizes histamine, may be involved in the development of ADHD. Our conceptual paper suggests that DAO enzyme deficiency may be involved in the development and severity of ADHD. Histamine, which is metabolized by DAO, plays an important role in the regulation of attention, memory and cognition. Therefore, decreased DAO activity could lead to an accumulation of histamine, which could contribute to ADHD symptoms. This study provides a theoretical framework for the relationship between DAO deficiency and ADHD, which could have important implications for the diagnosis and treatment of the disorder. Further empirical studies are needed to confirm our hypothesis and explore the clinical implications of the relationship between DAO deficiency, histamine, and ADHD.

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (Ca_Vs). Calcium entering through Ca_Vs is key for multiple neuronal processes. In this review, we will summarize recent findings that link Ca_Vs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of Ca_Vs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in Ca_V genes when available. We will review pharmacological evidence of the use of Ca_V modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of Ca_Vs.

Sarcasm is a linguistic expression often used to communicate the opposite of what is said, usually something that is very unpleasant with an intention to insult or ridicule. Inherent ambiguity in sarcastic expressions, make sarcasm detection very difficult. In this work, we focus on detecting sarcasm in textual conversations from various social networking platforms and online media. To this end, we develop an interpretable deep learning model using multi-head self-attention and gated recurrent units. Multi-head self-attention module aids in identifying crucial sarcastic cue-words from the input, and the recurrent units learn long-range dependencies between these cue-words to better classify the input text. We show the effectiveness of our approach by achieving state-of-the-art results on multiple datasets from social networking platforms and online media. Models trained using our proposed approach are easily interpretable and enable identifying sarcastic cues in the input text which contribute to the final classification score. We visualize the learned attention weights on few sample input texts to showcase the effectiveness and interpretability of our model.