Background: Maladaptive neuroplasticity related learned response in substance use disorder (SUD) can be ameliorated using non-invasive brain stimulation (NIBS); however, inter-individual variability needs to be addressed for clinical translation. Objective: Our first objective was to develop a hypothesis for NIBS for learned response in SUD based on competing neurobehavioral decision systems model. Next objective was to conduct computational simulation of NIBS of cortico-cerebello-thalamo-cortical (CCTC) loop in cannabis use disorder (CUD) related dysfunctional “cue-reactivity” – a closely related construct of “craving” that is a core symptom. Our third objective was to test the feasibility of our neuroimaging guided rational NIBS approach in healthy humans. Methods: “Cue-reactivity” can be measured using behavioral paradigms and portable neuroimaging, including functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG), metrics of sensorimotor gating. Therefore, we conducted computational simulation of NIBS, including transcranial direct current stimulation(tDCS) and transcranial alternating current stimulation(tACS) of the cerebellar cortex and deep cerebellar nuclei(DCN), of the CCTC loop for its postulated effects on fNIRS and EEG metrics. We also developed a rational neuroimaging guided NIBS approach for cerebellar lobule (VII) and prefrontal cortex based on healthy human study. Results: Simulation study of cerebellar tDCS induced gamma oscillations in the cerebral cortex while tTIS induced gamma-to-beta frequency shift. Experimental fNIRS study found that 2mA cerebellar tDCS evoked similar oxyhemoglobin(HbO) response in-the-range of 5x10-6M across cerebellum and PFC brain regions (=0.01); however, infra-slow (0.01–0.10 Hz) prefrontal cortex HbO driven(phase-amplitude-coupling, PAC) 4Hz, ±2mA (max.) cerebellar tACS evoked HbO in-the-range of 10-7M that was statistically different (=0.01) across those brain regions. Conclusion: Our healthy human study showed the feasibility of fNIRS of cerebellum and PFC as well as fNIRS-driven ctACS at 4Hz that may facilitate cerebellar cognitive function via the frontoparietal network. Future work needs to combine fNIRS with EEG for multi-modal imaging.

Visual exploration of complex data helps interpretation, especially in the case of omics data analysis in life sciences and clinical research. Generating and analysing omics data requires bioinformatic skills, while they are interpreted by domain experts, for whom parsing large and complex data structures may be challenging. However, outcomes of visual analytics are often difficult to quantify, which emphasises precision and reproducibility, especially for research on human diseases. Here, we propose a workflow combining a reproducible computational environment with a dedicated visualisation functionality for systems biology diagrams. By linking the Galaxy with the MINERVA Platform, we visualise and explore COVID-19 transcriptomic data to demonstrate the utility of our workflow. Visualised data recapitulate findings of the original publication and offer new insights about the COVID-19 pathology. Our results offer a blueprint for quick prototyping of computational workflows that facilitate communication and exploration of complex data in biomedical research.

Heart failure is a prevalent cardiovascular condition with significant health implications, necessitating effective diagnostic strategies for timely intervention. This study explores the potential of continuous monitoring of non-invasive signals, specifically integrating Photoplethysmogram (PPG) and Electrocardiogram (ECG), for enhancing early detection and diagnosis of heart failure. Leveraging a dataset from the MIMIC-III database, encompassing 682 heart failure patients and 954 controls. Feature selection techniques were used to systematically select key features which were identified for their clinical relevance and significance in capturing cardiovascular dynamics and to reduce computational complexity and to decrease the chance of overfitting the ML algorithms. These features are then utilized to train and evaluate machine learning algorithms, resulting in a model with an impressive accuracy of 98%, sensitivity of 97.60%, specificity of 96.90%, and precision of 97.20%. The integrated approach outperforms single-signal strategies, showcas-ng its potential for early, precise, and non-invasive heart failure diagnosis. Furthermore, the study underscores the significance of continuous monitoring through wearables, emphasizing the benefits of integrating multiple signals for a comprehensive evaluation of cardiovascular health. The proposed approach holds promise for implementation in hardware systems to enable continuous monitoring, aiding in early detection and prevention of critical health conditions.

Thyroid surgery rates have tripled over the past 3 decades making it one of the most frequently performed procedures within general surgery. They are associated with the possibility of serious postoperative complications having a significant impact on the patient's quality of life. The recurrent laryngeal nerve (RLN) palsy and the external branch of the superior laryngeal nerve (EBSLN) palsy are, next to hypoparathyroidism and bleeding after operation, one of the most common complications. The introduction of neuromonitoring into thyroid surgery, enabling both confirmation of anatomical integrity and assessment of laryngeal nerve function, was a milestone that has begun a new era in thyroid surgery. The International Neural Monitoring Study Group made standardization of the technique of RLN and EBSLN monitoring during thyroid and parathyroid surgery which increased prevalence of neural monitoring during thyroidectomy. Current status of IONM and benefits of its use have been presented in this publication.

Spinal muscular atrophy (SMA) is an orphan disease characterized by progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in the study. The median duration of drug treatment was over 20 months. Application of tSCS was performed during physical therapy for 20-40 minutes per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both types 2 and 3 SMA participants. The magnitude of functional changes was not associated with participants age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation in SMA.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Background: Pancreatic neuroendocrine tumors (pNETs) represents a rare subset of pancreatic cancer. Functional tumors caused hormonal changes and clinical syndromes, while non-functional ones are often diagnosed late. Surgical management need a multidisciplinary planning, involving enucleation, distal pancreatectomy with or without spleen preserving, cen-tral pancreatectomy, pancreaticoduodectomy or total pancreatectomy. Minimally invasive ap-proach increased in the last decade compared to the open technique. The aim of this study is to analyze current diagnostic and surgical trends for pNETs, to identify better interventions and their outcomes. Methods: The study adhered to PRISMA guidelines, conducting a systematic review of literature from May 2008 to March 2022 across multiple databases. Several combinations of keywords was used ("NET", "pancreatic", "surgery", "laparoscopic", "minimally invasive", "robotic”, “enuclea-tion”,“parenchima sparing”) and relevant article references was manually checked. Manuscript quality was evaluated. Results: The study screened 3867 manuscripts, twelve studies were selected, primarily from Ita-ly, the United States, and China. A total of 7767 surgical treated patients was collected from 160 included centers. The mean age was 56,3 y.o. Enucleations (EN) and distal pancreatectomy (DP) was the most common performed surgery and represents 43.4% and 38.6% of the total interven-tions, respectively. Pancreatic fistula, post operative bleeding, re-operation and follow up was recorded and analyzed. Conclusions: Enucleation show better postoperative outcomes and lower mortality rates com-pared to pancreaticoduodenectomy (PD) or distal pancreatectomy (DP), despite similar risks of postoperative pancreatic fistula (POPF). DP was preferred over enucleation for pancreas body-tail, while laparoscopic enucleation is better for head pNETs.

Technological advances in DBS hardware and software represent a significant growth area in functional neurosurgery. These advancements have the potential to significantly enhance treatment outcomes and expand the scope of neurological disorders that can be effectively addressed through DBS interventions. The introduction of directional DBS marks a new phase in neuromodulation, offering extended benefits for patients with Parkinson's disease, more efficient optimization of clinical outcomes, and targeted treatment of refractory symptoms through data-driven approaches. Implementing a multimodal programming strategy, incorporating novel current fractionation technology and image-guided tools for lead localization and brain sensing, further reduces reliance on traditional trial-and-error programming methods, paving the way for a more predictive application of this therapy. These advancements are expected to drive the development of sophisticated closed-loop stimulation systems capable of integrating continuous data streams for improved patient care.

Abstract Introduction: In the last thirty years, brain neuromodulation techniques have been used as an alternative to pharmacological treatment of neurological disorders. Parkinson's disease (PD) is a neurodegenerative disorder leading to bradykinesia, rest tremor, postural changes, and non-motor symptoms such as depression, anxiety, sleep disorders, pain, and cognitive decline that compromises executive functions (EFs), responsible for the orderly execution of behaviors and tasks of daily life and intentional and directed actions. To this date, a few studies with transcranial direct current stimulation (tDCS) have shown beneficial effects in PD patients concerning specific motor and non-motor symptoms, targeting the motor cortex and/or prefrontal regions. Objective: The main objective of this study was to evaluate the effects of left prefrontal tDCS across a broad spectrum of motor and non-motor symptoms of PD using established validated scales. Method: Single-blind randomized clinical trial with 18 volunteers with PD, aged between 45 and 80 years (66.1 ± 9.65), who met inclusion and exclusion criteria. Participants were submitted to assessments of motor and non-motor functions employing psychometric scales and tests to evaluate EFs and were randomly divided into two groups: control (sham stimulation) and experimental (active stimulation). All participants were involved in three separate tDCS sessions. The anode was positioned over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital region, with a direct current intensity of 2mA, lasting 20 minutes. At the end of the three sessions, all participants were reassessed. Results: Significant effects of tDCS on non-motor functions were observed for cognition (verbal fluency of actions, clock copy test, appointment by visual confrontation, and verbal memory with immediate free recall) and subjective assessment of sleep quality (overall restlessness and discomfort in the arms and legs at night, leg and arm cramps at night and distressing dreams). There was also an improvement in the rate of errors and successes for congruent and incongruent stimuli of the Stroop Test. The beneficial effects on motor function were decreased rigidity, improved gait, and greater agility in the finger-tapping test. Conclusion: Three tDCS sessions showed positive results for participants with PD, producing significant improvements in various motor and non-motor functions, including sleep quality, cognition, and EFs. Additionally, the present results indicate that tDCS neuromodulation of the left dorsolateral prefrontal cortex region is feasible, safe, and provides significant objective benefits for PD patients.

The European Green Deal poses a two-pronged challenge for the automotive industry: migrating to solutions based in light structures, requiring light weight concepts and light materials, while at the same time avoiding dependence towards the importation of these advanced materials. Aluminium alloys are lightweight and cost-effective materials that can successfully cover the requirements of many structural applications, however their production requires from bauxite and other Critical Raw Materials (CRM), such as Si and Mg. Aluminium alloys are fully recyclable, but scrap is usually contaminated and its use is related to an increment of impurities, tramp element and undesired inclusions. Traditionally, the use of secondary alloys has been restricted to low performance applications. The present work analyses the effect that the use of scrap has in the quantity of inclusions present in the alloy and in other properties relevant for the material processing. The study was carried out for common alloys belonging to 3 of the most common aluminium processes used in the car manufacturing industry: High Pressure Die Casting (HPDC) (EN AC-43500), extrusion (6063) and sheet metal forming (5754 and 6181). Reference alloy were mixed with different level of scrap (0, 20, 40, 60, 80 and 100%) trying to keep the chemical composition as unaffected as possible. The inclusions level of the alloy was characterized with the Prefil Foot-printer® test. In addition, the obtained materials, after being cast in an open mould, were subjected to metallographic characterization. Relevant properties to assess the formability quality of the alloys for the corresponding transforming process, were obtained: flowability test for HPDC alloy and high temperature compression for extrusion alloys. The results obtained suggest that the number of inclusions present in the melt highly increase with the amount of scrap used to produce the alloy. These inclusions are also related with an important lost of flowability, but do not have a noticeable impact on microstructure.

The origin of neurodegenerative diseases is linked to the abnormal folding of disease-associated proteins. The traditional amyloid hypothesis has been a focal point of research, but recent findings suggest a more complex picture. This review explores the role of physiological conformation of aggregation-prone domain (also known as prion-like low complexity domain) and multiple co-misfolded proteins in neurodegenerative diseases. We highlight the importance of targeting multi-heterotypic misfolded proteins for effective treatments and emphasize the irreversible neurodegeneration stemming from the loss of physiological folding in prion-like disease-causing proteins underscores the criticality of refolding. Additionally, we introduce the concept of ReproFold Therapeutics, a novel approach aimed at restoring the cellular prion-like folding of disease-causing proteins to rebuild normal cross-β interactomes and mitigate neurodegeneration. Baicalein, a potential drug candidate for this approach, shows promise in vitro and in animal models. Moreover, prion-like low complexity domains implicated in neurodegeneration are also associated with other disorders such as diabetes, cancers, and mental illnesses. Understanding the core pathology of neurodegenerative diseases and the broader implications of prion-like LC domains could revolutionize healthcare approaches and policies worldwide.

Tardive dyskinesia (TD) is a phenomenon predominantly observed as a result of the long-term use of dopamine receptor blockers (antipsychotics). TD is a group of involuntary, irregular hyperkinetic movements, mainly in the muscles of the face, eyelid muscles, lips, tongue, and cheeks, and less frequently in the limbs, neck, pelvis, and trunk. In some patients, TD takes on an extremely severe form, massively disrupting functioning, moreover, causing stigmatization and suffering. Deep brain stimulation (DBS), a method used, among others, in Parkinson's disease, is also an effective treatment for TD and often becomes a method of last resort, especially in severe, drug-resistant forms. The procedure is relatively new in TD, so the available reliable clinical studies are few and consist mainly of case reports. Unilateral and bilateral stimulation of two sites has proven efficacy in TD treatment. Most authors describe stimulation of the globus pallidus internus (GPi); less frequent descriptions involve the hypothalamic nucleus (STN). In the present paper, we provide up-to-date information on the stimulation of both mentioned brain areas. We also compare the efficacy of the two methods by comparing the two available studies, which included the largest groups of patients. Although GPi stimulation is more frequently used clinically, our initial analysis indicates comparable results (reduction of involuntary movements) with STN DBS.

Molecular analysis of growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

Over the last several years, large-scale cancer genomics studies involving multi region, multi-sample sequencing indicate that most or at least many cancer patients may have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. They can be identified via multiregion, multisample biopsies - or circulating tumor cells/cell-free DNA. Achilles Therapeutics is currently the only company targeting patient-specific, clonal mutations. They have opted to utilize an immunotherapy approach. However, I recently devised another approach for exploiting clonal mutations called “Oncolytic Vector Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). It is based on the identification of patient-specific, clonal mutations and targeting them using a bioengineered facultative intracellular bacterium. It would be initially non-replicating, but transiently regain the ability to replicate (and also transiently become hyper-virulent) upon mutation detection via molecular switches.

We presented unusual case of double left ventricular false aneurysm complicating late presentation AMI successfully treated with the combination of urgent surgical drainage of tamponade, staged PCI of non-culprit lesion, preventive implantation of ICD-DR, guideline directed heart failure medical therapy and delayed but effective reconstructive operation.

In the field of railroad safety, effective detection of surface cracks is critical, necessitating reliable, high-speed non-destructive testing (NDT) methods. This study introduces a hybrid Eddy Current Testing (ECT) probe, specifically engineered for railroad inspection, to address the common issue of ’lift-off noise’ due to varying distances between the probe and test material. Unlike traditional ECT methods, this probe integrates transmit and differential receiver coils, aiming to enhance detection sensitivity and minimize lift-off impact. The study optimizes ECT probes employing different driver coils, emphasizing three main objectives: a) quantitatively evaluating each probe using signal- to-noise ratio (SNR) and outlining a real-time data processing algorithm based on SNR methodology; b) exploring the frequency range proximal to the electrical resonance of the receiver coil; c) examining sensitivity variations across varying lift-off distances. The experimental outcomes indicate that the newly designed probe with figure 8-shape driver coil significantly improves sensitivity in detecting surface cracks on railroads. It achieves an impressive SNR exceeding 100 for defects with minimal dimensions of 1 mm in width and depth. Simulation results closely align with experimental findings, validating the investigation of optimal operational frequency and lift-off distance for selected probe performance, determined to be 0.3 MHz and 0.5 mm, respectively. The realization of this project would lead to notable advancements in enhancing railroad safety by improving crack detection efficiency.

The lymphatic system of the brain meninges and head plays a crucial role in the clearance of amyloid-β protein (Aβ), a peptide thought to be pathogenic in Alzheimer’s disease (AD), from the brain. The development of methods to modulate lymphatic clearance of Aβ from the brain coild be a revolutionary step in the therapy of AD. The opening of the blood-brain barrier (OBBB) by focused ultrasound is considered as a possible tool for stimulation of clearance of Aβ from the brain of humans and animals. Here, we propose an alternative method of non-invasive music-induced OBBB that is accompanied by the activation of clearance of fluorescent Aβ (Fαβ) from the mouse brain. Using confocal imaging, fluorescence microscopy and magnetic resonance tomography, we clearly demonstrate that OBBB by music stimulates the movement of Fαβ and Omniscan in the cerebrospinal fluid and lymphatic clearance of Fαβ from the brain. We propose the extended detrended fluctuation analysis (EDFA) as a promising method for the identification of OBBB markers in the electroencephalographic (EEG) patterns. These pilot results suggest that music-induced OBBB and the EDFA analysis of EEG can be a non-invasive, low cost, labelling free, clinical perspective and completely new approach for the treatment and monitoring of AD.

Type 2 Diabetes Mellitus is a chronic metabolic disease that poses a significant long-term health risk due to its debilitating complications. While the diagnosis and monitoring of diabetes are well-established, the monitoring of its numerous complications presents a challenge, which can compromise patients' prognosis and quality of life. We analyzed the proteome of ten saliva samples, five from healthy individuals and five from patients with Type 2 Diabetes Mellitus. The aim was to identify potential biomarkers of Type 2 Diabetes Mellitus and its complications. We used PANTHER and FUNRICH tools to conduct a functional analysis and enrichment approach. Our findings revealed 622 proteins involved in 16 disrupted biological processes, which are linked to Type 2 Diabetes Mellitus. Metabolic processes, response to stimuli, processes of the immune system, and signaling are notable due to their known relation with Type 2 Diabetes Mellitus. Enrichment analysis has revealed that there are eleven biological processes that have been deregulated. These processes involve twenty different salivary proteins that are associated with multiple complications in diabetes. Our findings demonstrate that saliva is a dependable source of possible biomarkers that can be used to monitor diabetes and its complications.

To this day, use of oily eye drops and non-invasive retinal delivery remains a major challenge. Oily eye drops usually cause ocular irritation and interfere with normal function of the eye, while ocular injections for retinal drug delivery cause significant adverse effects and a high burden on the healthcare system. Here the authors report a novel topical Non-Invasive Ocular Delivery Platform (NIODP) through the periorbital skin for high efficiency anterior and posterior ocular delivery in a non-human primate model (NHP). A single dose of about 7mg JV-MD2 (omega-3 DHA) via the NIODP reached the retina at Cmax of 111µg/g and the cornea at Cmax of 66µg/g. NIODP also delivered JV-DE1, an anti-inflammatory agent in development for dry eye diseases, as efficiently as eye drops did to anterior segments of NHP. The topical NIODP seems to transport drug candidates through the cornea pathway to the anterior and via the conjunctiva/sclera pathway to the posterior segments of the eye. The novel NIODP method has the potential to reshape the landscape of ocular drug delivery, especially for oily eye drops and retinal delivery, where the success of treatment lies in the ocular tolerability and bioavailability of drugs in the target tissue.

Involving industrial waste into economic circulation, in particular flotation waste from coal enrichment, is an urgent task. The coal preparation waste of ArcelorMittal Temirtau JSC was studied with a view to the possibility of using it as an alternative substitute for coke breeze in the sintering process. During a thermoanalytical study on a synchronous thermal analyzer STA 449 NETZSCH in dynamic mode with a heating rate of 10, 20, 30 °C/min in an air flow of 30 cm³/min in the temperature range 30–1000 °C, we determined the lower heat of combustion of carbon-containing material, change mass during calcination, change and rate of change in the mass of the sample, thermal effect of the process, the temperature of the beginning, end and maximum development of thermal effects. It has been established that the greatest mass loss is observed in the temperature range 580 °C- 610 °C, which is about 65–67% of the total mass of the organic component of coal. The maximum burnout rate corresponds to a temperature of 540–563 °C. The lowest calorific value of the studied waste was 15.9 MJ/kg. The results of thermal analytical research and technical analysis substantiate the possibility of using flotation waste in a mixture of up to 10% with coke breeze for combustion in the sintering layer for the production of sinter. Analysis of the composition of flotation waste showed that they have a high specific surface area (56.8∙10³ m²/kg), are highly dispersible, soggy, and capable of swelling, and the predominant amount of clay substance makes them a plastic material. The possibilities of using coal flotation waste as an alternative substitute for coke breeze have been studied after the regimes of its preparation for sintering have been developed and a rational regime of layer-by-layer combustion in the sintering layer has been established. The optimal ratio of coke and OPC in the fuel mixture of the sintering charge was determined.

Brain-stimulation reward, also known as intracranial self-stimulation (ICSS), is a commonly used procedure for studying brain reward function and drug reward. In electrical ICSS, an electrode is surgically implanted into the medial forebrain bundle in the lateral hypothalamus or the ventral tegmental area in the midbrain. Operant lever responding leads to the delivery of electrical pulse stimulation. The alteration in the stimulation frequency-lever response curve is used to evaluate the impact of pharmacological agents on brain reward function. If a test drug induces a leftward or upward shift in the ICSS response curve, it implies a reward-enhancing or abuse-like effect. Conversely, if a drug causes a rightward or downward shift in the functional response curve, it suggests a reward-attenuating or aversive effect. A significant drawback of electrical ICSS is the lack of cellular selectivity in understanding the neural substrates underlying drug reward versus aversion. Excitingly, recent advancements in optical ICSS (oICSS) have facilitated the development of at least three cell type-specific oICSS models – dopamine-, glutamate-, and GABA-dependent oICSS. In these new models, a comparable frequency-rate response curve has been established and employed to study the substrate-specific mechanisms underlying brain reward function and a drug's rewarding versus aversive effects. In this review article, we summarize recent progress in this exciting research area. The findings in these new behavioral models have not only increased our understanding of the neural mechanisms underlying drug reward and addiction but have also introduced a novel experimental approach in preclinical medication development for treating substance use disorders.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes, despite the prevalent recurrence and progression among many patients. In particular, flat urothelial car-cinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new‐generation photosensitizer, 5‐Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence, and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes.

Predetermined physical properties cannot manifest at the same time if they are mutually exclusive. As part of a single system, they become observable at different times, in sequence. In this case, pairwise detections in a narrow window of coincidence allow for maximal Bell violations (S=4 for the CHSH protocol), without room for doubt about the local nature of the process. This shows that a deeper description of physical reality is possible, as suggested by Einstein, Podolsky and Rosen. Though, a more inclusive definition of Realism is required, in order to account for Bohr’s Contextuality.

Deep brain stimulation (DBS) is an effective and safe medical treatment that improves the lives of patients with a wide range of neurological and psychiatric diseases, and has been consolidated as a first-line tool in the last two decades. Closed loop deep brain stimulation (CLDBS) pushes this tool further by automatically adjusting the stimulation parameters to the brain response in real-time. This paper presents a CLDBS with 2 stimulation channels and 2 acquisition channels. Each channel has a low-noise amplifier (LNA) buffer in differential configuration to eliminate the DC signal component of the input. Energy management is efficiently done by the control and communication unit. The battery supports almost 9 hours with both the acquisition and stimulation circuits active. If only the stimulation circuit is used as an Open Loop DBS (OLDBS), the battery can hold sufficient voltage for 24 hours of operation. The whole system is low-cost and portable and therefore it could be used as a wearable.

Spinal Cord Stimulation (SCS) is an effective and validated treatment to address chronic refractory neuropathic pain in Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients. Surgical SCS lead placement is traditionally performed under general anesthesia due to its invasiveness. In parallel, recent works have suggested that Awake Anesthesia (AA), consisting in Target Controlled Intra-Veinous Anesthesia (TCIVA), could be an interesting tool to optimize lead anatomical placement using patient intra-operative feedback. We hypothesized that combining AA with Minimal Invasive Surgery (MIS) could improve SCS outcomes. The goal of this study was to evaluate SCS lead performance (defined by the area of pain adequately covered by paraesthesia generated via SCS), using an intraoperative objective quantitative mapping tool, and secondarily to assess pain relief, functional improvement and change in quality of life with a composite score. We analyzed data from a prospective multicenter study (ESTIMET) to compare the outcomes of 115 patients implanted with MIS under AA (MISAA group) or General Anesthesia (MISGA group), or by Laminectomy under General Anesthesia (LGA group). All in all, MISAA appears to show significantly better performance in terms of patient pain coverage, as well as improved secondary outcomes. One step further, our results suggest that MISAA combined with intra-operative hypnosis could potentialize patient intraoperative cooperation and could be proposed as a personalized package offered to PSPS-T2 patients eligible for SCS implantation in highly dedicated neuromodulation centers.

Deep-Brain Stimulation (DBS) is a a highly effective and safe medical treatment that improves the lives of patients with a wide range of neurological and psychiatric deceases, and has been consolidated as a first-line tool in the treatment of these conditionsin the last two decades. Closed Loop Deep-Brain Stimulation (CLDBS) pushes this tool further by automatically adjusting the stimulation parameters to the brain response in real time. In this context, this paper presents a Low-Noise Amplifier (LNA) and a Neurostimulator circuits fabricated in the low-power/low-voltage 65 nm CMOS process from the TSMC, which were designed targeting implantable applications. To achieve the best trade-off between input-referred noise and power consuption, metaheuristic algorithms were employed to determine and optimizes the dimentions of the LNA devices during the design phase. The measurement results showed that the LNA had a gain of 40.6 dB, a 3 dB bandwidth spanning over three decades from 10 Hz to 8.6 kHz, and a power consumption of 6.19 uW. Simulations results indicated an input-referred noise of 4.86 uVrms for the LNA. The circuit of the Neurostimulator is a programmable Howland Current-Pump, whose measurements showed its ability to generate currents with arbitrary shapes ranging from between 325 uA to +318 uA. The simulations showed a quiescent power consumption of 0.13 W with a zero neurostimulation current. The LNA and the Neurostimulator circuits are supplied with 1.2 V voltage and occupy a microdevice area of 145 um x 311 um and 88 um x 89 um, respectively, making them suitable for implantation in applications involving Closed Loop Deep-Brain Stimulation.

Previous studies on the mechanisms underlying willed actions reported that the premotor cortex may be involved in the construction of motor awareness. However, its exact role is still under investigation. Here we investigated the role of the dorsal premotor cortex (PMd) in motor awareness by modulating its activity applying inhibitory rTMS to PMd, before a specific motor awareness task (under three conditions: without stimulation, after rTMS and after sham stimulation). During the task, subjects had to trace straight lines to a given target, receiving a visual feedback of the line trajectories on a computer screen. Crucially, in most trials the trajectories on the screen were deviated and to produce straight lines, subjects had to correct their movements towards the opposite direction. After each trial, participants were asked to judge whether the line seen on the computer screen corresponded to the line actually drawn. Results show that participants in the no stimulation condition did not recognize the perturbation until 14 degrees of deviation. Importantly, active, but not sham, rTMS significantly modulated motor awareness, decreasing the amplitude of the angle at which participants became aware of the trajectory correction. These results suggest that PMd plays a crucial role in action self- monitoring.

Aileen Oeberst and Roland Imhoff’s remarkable paper (Perspectives on Psychological Science 2023; 18: 1464-87). should be compulsory reading for all intelligence analysts. It offers a tantalisingly parsimonious explanation comprising the combination of strongly held prior 'beliefs' coupled with subsequent 'belief-consistent information processing' (akin to confirmation bias) - an explanation that simplifies understanding of a vast array of cognitive biases, and thereby suggests that all of these might be attenuated through the application of accessible analytical and assessment practices. What this means for intelligence analysis will be determined by the explicit and implicit 'beliefs' (or, more generally, ‘value[s]’) attributed to any evidence available, and any insight generated, to reduce decision-makers’ uncertainty and unsubstantiated certainty, and thereby offer them future advantage. Analysts are well aware that different sources of evidence (whether empirical, theoretical or entirely speculative) can assign different types and amounts of ‘prior value’ to the information available for intelligence analysis and assessment. Acknowledging such value as a potential driver of subsequent confirmation bias should help analysts guard against any inherent tendency to preference evidence solely on the basis that this was initially considered most ‘valuable’. Instead they should subject all evidence and all insight – regardless of perceived ‘value’ – to a consistent battery of systematic, rigorous and robust evaluation.

Continual learning, a crucial facet of machine learning, involves the perpetual acquisition of valuable insights from incoming data, sans the necessity for full dataset access. Esteemed as a fundamental goal in artificial intelligence, continual learning grapples with an enduring challenge—catastrophic forgetting. A proficient model must exhibit adaptability for new data assimilation and robustness to retain existing knowledge. Class-incremental learning (CIL) aids the gradual integration of knowledge from newly introduced classes, forming a universal classifier. However, directly training the model with fresh class instances triggers a problem—forgetting distinguishing features of prior classes, causing a performance decline. Addressing such issues in machine learning, this survey aims to delineate significant challenges, outcomes, and recent advancements, including our contributions to CIL techniques, especially in image classification.

The introduction of ventricular shunts dramatically changed the outcome and quality of life of hydrocephalic patients. However, shunt surgery continues to be associated with numerous adverse events. Headache is one of the most common complications after shunt operation. It is often over a prolonged duration, the symptoms resemble migraine, and pain does not respond to medication. We propose invasive peripheral nerve stimulation as a possible solution in the treatment of patients suffering from chronic headache associated with shunted hydrocephalus. A young woman with daily holocephalic headache with diffuse pain exacerbated by lying down. Imaging revealed panventricular enlargement and possible stenosis of the aqueduct. When a ventriculoperitoneal shunt was placed, clinical symptoms resolved. Nevertheless, she gradually exacerbated after a second valve replacement due to wound infection. Imaging revealed decompressed ventricles and appropriate shunt placement. The diagnosis of chronic post-intracranial disorder headache was set. Therefore, occipital nerve stimulation was applied and considering that the patient had not a total response, bilateral parietal stimulation was added. Three months after the combined PNS she experienced total remission of headache. Combined PNS eases refractory headaches much more than occipital nerve stimulation alone and could be considered as a solution for shunted hydrocephalus associated headache.

Spinal cord injuries (SCI) can result in sensory and motor dysfunctions, which were long-considered permanent. Recent advancement in electrical neuromodulation has been proven to restore sensorimotor function in people with SCI. These stimulation protocols, however, were mostly invasive, expensive, and difficult to implement. In this study, transcutaneous electrical stimulation (tES) was used to restore over-ground walking of an individual with 21 years of chronic paralysis from a cervical SCI. After a total of 66 weeks of rehabilitation training with tES, which included standing, functional reaching, reclined sit-up, treadmill walking and active biking, significant improvement in lower-limb volitional movements and overall light touch sensation were shown by International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score. By the end of the study, the participant could walk in a 4-meter walking test with the aid of a walking frame and ankle foot orthoses. The success in the sensorimotor recovery of our study participant sheds light on the future of non-invasive neuromodulation treatment for SCI paralysis.

Although all isolates of the foodborne pathogen Listeria monocytogenes are considered to be pathogenic, epidemiological evidence indicates that certain serovar 4b lineages are more likely to cause severe invasive (neuromeningeal, maternal-fetal) listeriosis. Recently described as L. monocytogenes “hypervirulent” clones, no distinctive bacterial trait has been identified so far that could account for the differential pathogenicity of these strains. Here we discuss some preliminary observations in experimentally infected mice suggesting that serovar 4b hypervirulent strains may have a hitherto unrecognized capacity for prolonged in vivo survival. We propose the hypothesis that protracted survivability in primary infection foci in liver and spleen –first target organs after intestinal translocation– may cause L. monocytogenes serovar 4b hypervirulent clones to have a higher probability of secondary dissemination to brain and placenta.

To investigate the impact of electrode structure on Electrical Stimulation Therapy (EST) for chronic wound healing, this study designed three variants of flexible microelectrodes (FMs) with Ag-Cu coverings (ACCs), each exhibiting distinct geometrical configurations: hexagonal, cross-shaped, and serpentine. These were integrated with PPY@PDA/PANI (3/6) hydrogel dressings. Comprehensive animal studies, coupled with detailed electrical and mechanical modeling and simulations, were conducted to assess their performance. Results indicated that the serpentine-shaped FM outperformed its counterparts in terms of flexibility and safety, exhibiting minimal thermal effects and a reduced risk of burns. Notably, FMs with metal coverings under 3% demonstrated promising potential for optoelectronic self-powering capabilities. Additionally, simulation data highlighted the significant influence of hydrogel non-uniformity on the distribution of electrical properties across the skin surface, providing critical insights for optimizing EST protocols when employing hydrogel dressings.

Background: Preterm birth is a major cause of morbidity and mortality in infants and children. Non-invasive methods for screening the neonatal immune status are lacking. Archaea, a prokaryotic life domain, comprise methanogenic species that are part of the neonatal human microbiota and contribute to early immune imprinting. However, they have not yet been characterized in preterm neonates. Objective: To characterize the gut immunological and methanogenic Archaeal (MA) signature in preterm neonates, using the presence or absence of atopic conditions at the age of 1 year as a clinical endpoint. Methods: Meconium and stool were collected from preterm neonates and used to develop a standardized stool preparation method for the assessment of mediators and cytokines and characterize the qPCR kinetics of gut MA. Analysis addressed the relationship between immunological biomarkers, Archaea abundance, and atopic disease at age 1. Results: Immunoglobulin E, tryptase, calprotectin, EDN, cytokines, and MA were detectable in the meconium and later samples. Atopic conditions at age 1 year were positively associated with neonatal EDN, IL-1β, IL-10, IL-6, and MA abundance. The latter was negatively associated with neonatal EDN, IL-1β and IL-6. Conclusion: We report a non-invasive method for establishing a gut immunological and Archaeal signature in preterm neonates, predictive of atopic diseases at the age of 1 year

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition include bacterial contamination, tissue perfusion, and mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments.In this review, we discuss bioengineering advances in non-invasive detection of biologic and physiologic factors of the healing wound, visualizing and modeling the ECM, and computational tools to efficiently evaluate the complex data acquired from the wounds to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the matrix, linearity of collagen, and live tracking of components within the ECM. Computational modeling of the matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed.

The liver is a key node of whole-body nutrient and fuel metabolism and is also the principal site for detoxification of xenobiotic compounds. As such, hepatic metabolite concentrations and/or turnover rates inform the status of both hepatic and systemic metabolic diseases as well as the disposition of medications. As a tool to better understand liver metabolism in these settings, in vivo magnetic resonance spectroscopy (MRS) offers a non-invasive means of monitoring hepatic metabolic activity in real time both by direct observation of concentrations and dynamics of specific metabolites as well as by observation of their enrichment by stable isotope tracers. This review summarizes the applications and advances in human liver metabolic studies by in vivo MRS over the past 35 years and discusses future directions and opportunities that will be opened by the development of ultra-high field MR systems and by hyperpolarized stable isotope tracers.

The Pygmy hog (Porcula Salvania), till recently, classified as a critically endangered suid, is facing the threat of extinction globally due to habitat degradation. Efforts are being made to protect the pygmy hogs from extinction and breed them in captivity under Pygmy Hog Conservation Pro-gramme (PHCP). However, very little information is available on the reproductive physiology of pygmy hogs. Therefore, the present study aimed to standardize enzyme immunoassays (EIAs) for monitoring pregnancy and reproductive status using progesterone and testosterone metabolites. A total of 785 faecal samples were collected from five females and two males over a period of one year from PHCP Research and Breeding Centre, Guwahati, Assam. High-pressure liquid chro-matography (HPLC) analysis revealed the presence of immunoreactive progesterone and testos-terone metabolites in faeces. Mating was observed in all the five females and four of them gave birth successfully. We were able to detect pregnancy using faecal progesterone metabolites. Based on mating and parturition, the mean gestation period was estimated to be 153.25 days from four females. The breeding centre recorded 172 births between 1996 and 2000 and found strong sea-sonality in births and most of the births were between May and June. Faecal testosterone metabo-lites were significantly higher in the breeding season than the non-breeding season. This is the first study and will help in future breeding programs in other captive breeding centres and reproduc-tive monitoring of reintroduced populations.

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring.In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63-100%, 90-95%, 47-97%, respectively) while minimizing stress and discomfort for the patient.

Counterfeiting electronic components is a serious problem for the security and reliability of any electronic systems. Unfortunately, the number of counterfeit components has increased considerably after the introduction of horizontal semiconductor supply chain. In this paper, we propose a new method for detecting recycled Flash memory, a major target of the counterfeiters due to its ubiquitous usage. Proposed method is based on measurement of change in Flash array characteristics (such as erase time, program time, fail bit count, etc.) with its usage. We find that erase time is the best metric to distinguish a used Flash chip from a fresh one for the following reasons: (1) erase time shows minimal variation among different fresh memory blocks/chip and (2) erase time increases significantly with usage. We verify our method for a wide range of commercial off the shelf Flash chips from several vendors, technology nodes, storage density and storage type (single-bit per cell and multi-bit per cell). The minimum detectable chip usage varies from 0.05% to 3.0% of its total lifetime depending on the exact details of the chip.

Tremor is a prevalent symptom associated with multiple conditions, including Essential Tremor (ET), Parkinson’s disease (PD), multiple sclerosis (MS), stroke, and trauma. The surgical management of tremor evolved from stereotactic lesions to deep-brain stimulation (DBS), which allowed safe and reversible interference with specific neural networks. This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets (Vim, Raprl, caudal Zi, Vo and STN) and continuing with a discussion of results obtained when performing DBS in the various aforementioned tremor syndromes. Future directions for DBS research are then briefly discussed.

Heart transplantation (HT) represents the mainstream therapy of end-stage heart failure for selected patients with a median survival of more than 10 years after surgery and substantial improvement in quality of life. Current guidelines suggest a variety of examinations including invasive (coronary angiography and endomyocardial biopsy (EBM) and non-invasive methods (echocardiography, stress echocardiography, computed tomography, PET and MRI) to monitor HT patients. Guidelines do not specify the timing of echocardiographic evaluations and do not recommend echocardiography as an alternative to serial EMB in rejection monitoring [2]. They still recommend as gold standard coronary angiography to be done 1 year after surgery and every 2 years after. In this review we will discuss the advantages of non-invasive techniques over the invasive ones for an adequate follow-up of HT patients.

Reliable quantification of pulmonary arterial pressure is essential in the diagnostic and prognostic assessment of a range of cardiovascular pathologies including rheumatic heart disease, yet an accurate and routinely available method for its quantification remains elusive. This work proposes an approach to infer pulmonary arterial pressure based on scientific machine learning techniques and non-invasive, clinically available measurements. A 0-D multicompartment model of the cardiovascular system was optimized using several optimization algorithms, subject to forward-mode automatic differentiation. Measurement data were synthesized from known parameters to represent the healthy, mitral regurgitant, aortic stenosed and combined valvular disease situations with and without pulmonary hypertension. Eleven model parameters were selected for optimization based on 95 % explained variation in mean pulmonary arterial pressure. A hybrid Adam and limited-memory Broyden-Fletcher-Goldfarb-Shanno optimizer yielded the best results with input data including valvular flow rates, heart chamber volume changes and systematic arterial pressure. Mean absolute percentage errors ranged from 1.8 % to 3.78 % over the simulated test cases. The model was able to capture pressure dynamics under hypertensive conditions with pulmonary arterial systole, diastole, and mean pressure average percentage errors of 1.12 %, 2.49 % and 2.14 %, respectively. The relatively low errors highlight the potential of the proposed model to recover pulmonary pressures for diseased heart valve and pulmonary hypertensive conditions.

This study reports a correlation between EEG and structural brain changes in patients after severe traumatic brain injury in a coma. The novelty of our approach was based on the combination of structural visualization (MRI) and functional neuroimaging (EEG) during tactile stimulation. The structural morphometry indicated a decrease of whole-brain cortical thickness, the gray-matter volume of the cortex, and subcortical structures in comatose patients compared to healthy subjects. In resting-state EEG, coma patients had significantly higher power of the slow-wave activity of 2-6 Hz and significantly less power of the alpha and beta rhythm. Importantly, coma patients showed a significant decrease of theta-rhythm power in tactile stimulation compared to the resting state, and this EEG pattern was not found in the control group. The decrease of the theta-rhythm power significantly correlated with the better outcome from a coma. Spectral changes in EEG in response to tactile stimuli showed no association with brain morphometric measures in healthy controls. In patients, decreasing theta-rhythm power correlated positively with the volume of whole-brain gray matter, right putamen, and insula; and negatively with the volume of damaged brain tissue. Increasing beta-rhythm power, specific tactile EEG response for a healthy brain, correlated with the cortical thickness of the somatosensory Paracentral and Precentral area. The observed decrease of gray-matter volume indicates brain atrophy in coma patients, which could be associated with neurodegeneration induced by injury. Our results also demonstrate that slow-wave desynchronization, as a nonspecific response to tactile stimulation, can serve as a sensitive index of morphometric changes after brain injury and coma outcome.

Current commercial, pre-commercial, and experimental in ovo techniques for the sex determination of fertilised eggs employ either minimally invasive biomolecular assays (extracting fluid via a small laser-drilled window in the eggshell, for detection of genetic or hormonal biomarkers), analysis of volatile compounds emitted from the eggshell, visible imaging, and reflectance or transmission spectroscopic analysis exploiting molecular optical fluorescence, polarisation, and scattering phenomena, including various combinations of these modalities. , to date no endeavour employing the NIR and FTIR based spectroscopic techniques has resulted in a commercially sustainable solution to the egg sexing problem. Besides achieving only subpar performance in overall accuracy, specificity, and sensitivity, the least invasive of the current state-of-the-art optical methods still requires, creating a transmission window (fenestration) of 12–15 mm diameter through to the mammillae layer of the shell, proximal to the external shell membrane, which can affect the incubation or post-hatch development viability of up to 10% of incubated eggs. Multimodal solution combining Raman spectroscopy and hyperspectral imaging has strong prospects to overcome the hard barriers existing before the perfection of a non-invasive in-line process for high reliability and rapid throughput for sex determination of eggs within 3 days of incubation. The method for sexing of chicken embryos needs to take a multipronged approach in collecting and analyzing spectral data that points to biomarkers using the machine learning approaches to look for nanomolar to picomolar concentrations of these in the fluid.

Sialylated milk oligosaccharides (SMOs) is the most important oligosaccharides in human milk oligosaccharides (HMOs), and have a multifunctional health benefit, and the most abundant SMOs are sialyllactose (SLs). The previous studies indicate that the growth of tumor cells, and angiogenesis on tumor tissues with Lewis lung carcinoma, melanoma, and colon carcinoma cells could be prevented by SL. Thus, it has been proposed that SL might be an ideal candidate for the development of anti-angiogenic drugs without any side effects. It has been proposed that the Sialic acid (Sia) can be produced through SL’s hydrolysis, and the dietary Sia is further transported to the brain and other tissues though blood for formation of CMP-Sia, the activated precursor of Sia, and then is catalyzed by polysialyltransferases (polySTs) for synthesis of polysialic acid (polySia) or polysialylation of neural cell adhesion molecule (NCAM). Thus, it’s necessary to study and develop new inhibitors, which not only modulate a proper balance between the gut health and neuros system development, but also inhibit the overexpression of polySia, and thus block the tumor cell migration. In this study, we proposed that 3’-SL and 6’-SL may be more ideal inhibitors comparing with two previous inhibitors, the low molecular weight heparin (LMWH) and cytidine monophosphate (CMP) in the previous studies.

(1) Background: Alzheimer’s disease (AD) presents a significant challenge in terms of discovering novel diagnostic methods and therapies. Previous research has shed light on the neuroprotective properties of Apelin-13 in neurodegenerative disorders. However, elucidating the mechanism underlying its efficacy in combating AD-related nerve injury is imperative. In this study, we aimed to investigate the mechanism of action of Apelin-13 in an in vivo model of AD induced by streptozocin (STZ); (2) Methods: We utilized an STZ-induced nerve injury model of AD in mice to investigate the effects of Apelin-13 administration. The Apelin-13 was administered intranasally, and cognitive impairment was assessed using standardized behavioral tests. The main methods included behavioral assessment, histological analysis, and biochemical assays to evaluate synaptic plasticity and oxidative stress signaling pathways; (3) Results: Our findings indicate that intranasal administration of Apelin-13 ameliorated cognitive impairment in the STZ-induced AD model. Furthermore, we observed that this effect was potentially mediated through the enhancement of synaptic plasticity and attenuation of oxidative stress signaling pathways; (4) Conclusions: The results of this study suggest that intranasal administration of Apelin-13 holds promise as a therapeutic strategy for preventing neurodegenerative diseases such as AD. By improving synaptic plasticity and mitigating oxidative stress, Apelin-13 may offer a novel approach to neuroprotection in AD and related conditions.

The secondary structures of Scherer commonly known as perineuronal and perivascular satellitosis have been identified as a histopathological hallmark of diffuse, invasive, high-grade gliomas. They are recognized as perineuronal satellitosis when clusters of neoplastic glial cells surround neurons cell bodies and perivascular satellitosis when such tumour cells surround blood vessels infiltrating Virchow-Robin spaces. In this review, we provide an overview of emerging knowledge regarding how interactions between neurons and glioma cells can modulate tumour evolution and how neurons play a key role in glioma growth and progression, as well as the role of perivascular satellitosis into mechanisms of glioma cells spread. At the same time, we review the current knowledge about the role of perineuronal satellitosis and perivascular satellitosis within the tumour microenvironment (TME), in order to highlight critical knowledge gaps in research space.

This study aimed to investigate the relationship between sleep duration, dementia severity, age, and ANS regulation. This cross-sectional pilot study included 27 older patients with probable Alzheimer’s disease, hospitalized at a psychiatric center. We measured heart rate variability to assess ANS regulation at night, evaluated dementia severity using the Clinical Dementia Rating scale, and obtained sleep duration data from sleep diaries maintained by psychiatric nurses. The data were analyzed using repeated-measures generalized linear models with age, sex, dementia severity, and medication (antipsychotics) as covariates. A sleep duration of 7–8 h per night was associated with better ANS regulation than other sleep durations, as indicated by sympathovagal balance (p = 0.005). ANS dysregulation was characterized by a 20.7% increase in sympathetic nervous system activity and a 14.8% decrease in parasympathetic nervous system (PSNS) activity. We found a significant correlation between dementia severity and PSNS activity (p = 0.04) and observed an inverted U-shaped association between sleep duration and ANS regulation. This pilot study demonstrated that a sleep duration of 7–8 h per night may be critical in maintaining optimal ANS regulation. Bidirectional associations between sleep duration, inadequate sleep duration, aging, and ANS regulation warrant further investigation.

Researchers and organizations are pursing 100 Day Vaccine Development to reduce the impact of any new pandemic-causing virus. They propose monitoring viral emergence and developing vaccines for discovered viruses which would undergo safety testing in humans. If one of these viruses emerges, phase III trials would then take place. There are two problems with this approach - first, phase III trials are too long for the 100-day goal and second, the virus that emerged might not have been discovered in their surveillance. An alternative approach would be to first develop vaccines for viral families similar to the pan coronavirus vaccines being proposed for next generation COVID vaccines. Phase III trials for them would be run even if a virus in the family wasn’t having an outbreak. If a virus in a family for which a vaccine has been developed has an outbreak and the phase III trialed vaccine is not effective against it, develop a booster based on the phase III trialed vaccine. Since booster development and approval takes less than 100 days, the 100 Day Vaccine Development goal would be met.

A 12 year old boy was diagnosed with temporal lobe epilepsy (TLE) along with mesial temporal sclerosis based on MRI (magnetic resonance imaging) results. The diagnosis was further confirmed by genetic analysis. He also had minor psychiatric symptoms of obsessive-compulsive disorders and mood swings. After 4 years of treatment with Sodium Valproate no change in symptoms was observed. Genetic testing along with deep phenotyping revealed altered glutamate pathway and metabolism. Post genetic testing the patient was put on a combination of Sodium Valproate and Valproic acid along with supplementation of N-acetylcysteine (NAC), Cyanocobalamin, Pyridoxine and Cholecalciferol. Within three months of this combined therapy the patient experienced complete elimination of seizures and drastic improvement in mood and social behaviour. The case report highlights the importance of precision diagnosis in understanding the underlying perturbed pathways in structural epilepsy like TLE and demonstrates the importance of non-invasive targeted therapy in such cases.

Postural instability (PI) in Parkinson’s disease (PD) exposes patients to increased risk of falls (RF). Although dopaminergic therapy and deep brain stimulation (DBS) improve motor performance in advanced PD patients, their effects on PI and RF are not clear. PI and RF were assessed by a stabilometric platform in 6 advanced PD patients. Patients were evaluated on and off dopaminergic medication and four DBS conditions: bilateral-DBS, DBS of the more- or less-affected side and DBS-off. Dopaminergic medication alone worsened PI and RF, DBS alone worsened RF, and no medication/DBS combination produced an improvement in postural control with respect to the OFF-medication/DBS-off condition. When ON-medication, PI and RF significantly improved after turning the DBS on, regardless of medication condition. Among DBS conditions, bilateral-DBS provided the maximal improvement of PI and RF when ON medication, and minimal worsening of PI and RF when OFF medication, whereas patients performed worse when in most-affected side DBS condition. These results can help in developing the best therapeutic strategy for postural disorders in patients with advanced PD.

The cough assessment is fundamental in the weaning process as it gives information on the possibility to expel food and secretion from the airways. The majority of persons suffering from severe acquired brain injury (ABI) are not able to cough voluntarily due to severe motor deficits. In the present study, we evaluated the cough reflex in ABI patients using a new method based on a capsaicin spray stimulation test. 100 Healthy controls demographically matched with 50 ABI patients were included in this study. Clinical observations demonstrated robust cough response in both healthy controls and ABI patients, as well as the safety and tolerability of capsaicin spray stimulation. ABI patients with dysphagia were characterized by slower and delayed cough responses. Further studies are needed to validate this feasible, less-invasive, and simple-to-comprehend technique in inducing cough reflex. According to this preliminary evidence, we believe that this test might be translated into a simple and effective treatment to improve cough strength training reflexive cough modulation in ABI patients.

Accurate classification of objects in 3D point clouds is a significant problem in several applications, such as autonomous navigation and augmented/virtual reality scenarios, which has become a research hot spot. In this paper, we presented a deep learning strategy for 3D object classification in augmented reality. The proposed approach is a combination of the GRU and LSTM. LSTM networks learn longer dependencies well, but due to the number of gates, it takes longer to train; on the other hand, GRU networks have a weaker performance than LSTM, but their training speed is much higher than GRU, which is The speed is due to its fewer gates. The proposed approach used the combination of speed and accuracy of these two networks. The proposed approach achieved an accuracy of 0.99 in the 4,499,0641 points dataset, which includes eight classes (unlabeled, man-made terrain, natural terrain, high vegetation, low vegetation, buildings, hardscape, scanning artifacts, cars). Meanwhile, the traditional machine learning approaches could achieve a maximum accuracy of 0.9489 in the best case.

Abstract: Brassinosteroids (BR) are essential plant hormones that play a crucial role in regulating plant growth and development, as well as their resistance to abiotic and biotic stresses, including pathogen infections. In the context of plant im-munity, BR influence various processes such as the expression of genes related to pathogen defense, the production of antimicrobial compounds, and the re-inforcement of the plant cell structure. The aim of work is understand the role of BR in plant defense against abiotic and biotic stresses. BR are involved in the regulation of metabolic processes, water economy, and photosynthesis, contributing to increased plant resistance to abiotic stresses. The study discusses various mechanisms of BR action on plant immunity, including the regulation of gene expression related to defense, activation of the plant defense system, in-teraction with other plant hormones, regulation of water and salt balance, and influence on photosynthetic processes. In the context of plant immunity, BR influence various processes, including the expression of genes related to pathogen defense, the production of antimicrobial compounds, and the reinforcement of the plant cell structure. Additionally, BR are involved in the regulation of metabolic processes, water economy, and photosynthesis, con-tributing to increased plant resistance to abiotic and biotic stresses. The paper emphasizes the importance of further research on the role and mechanisms of action of BR in plant immunity, which may contribute to the development of more effective strategies for the use of BR in agriculture, horticulture, and plant protection.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

Burn patients still represent an important challenge in critical care medicine today. These patients can develop significant neurological conditions up to intracranial hypertension, but as they find themselves hospitalized outside of neurocritical care and are often subjected to sedation for the complex management, they are sometimes underestimated. The aim of this study is to evaluate the feasibility of non-invasive methods for the early diagnosis of intracranial hypertension in these patients. In this prospective observational study, adult burn patients admitted to intensive care within the first 8 hours of the event were enrolled. These patients were studied through ultrasound measurement of optic nerve sheath diameter and intracranial vessel velocimetry with transcranial Doppler. In the 20 patients studied, no frankly pathological values were identified in the 3 different measurement stages (within 8 hours of the burn, then at 48 and 96 hours) and no correlations were identified between the measured values and the extension of the burn with the related risk of mortality. However, this study, one of a kind, demonstrates that these non-invasive methods are applicable to this specific patient population, and can represent an effective method for reducing the incidence of complications that are dangerous for survival.

Continuous glucose monitoring devices allow diabetes condition management. However, when limited data is available, one option is to increase their size by generating synthetic samples. From a homemade wearable prototype was created a real dataset with 18 instances and 53 attributes that capture characteristics of capillary and venous blood glucose, oxygen concentration, pulse rate, skin temperature, and 24 modules and 24 phases related to bio-impedance. The objective of this article is to generate synthetic datasets, and also it investigates the ideal features subset and optimal model for non-invasive diabetes prediction. Gaussian-Copulas (GC), conditional generative adversarial networks (CG), variational autoencoders, and Copula-GAN techniques' were used to generate five synthetic datasets. Experiments show that GC1 and GC2 datasets follow min/max boundaries and are not copies of the original data. Multilayer perceptron regressor outperformed (train and test) with 2.17, 2.51 in MAE; 9.29, 13.59 in MSE; 3.05, 3.69 in RMSE, and 0.95, 0.92 in R2 in GC1, and 2.64, 3.02 in MAE; 11.43, 15.11 in MSE; 3.38, 3.89 in RMSE, and 0.94, 0.92 in R2 in GC2 with eight features. Future work is necessary to explore autoencoder and generative architectures, datasets with diverse characteristics, and the effect of the number of features.

Keywords: flow mediated skin fluorescence; FMSF technique; NADH fluorescence, microcirculation, flowmotion, reactive hyperemia response, RHR, hypoxia sensitivity, HS, normoxia oscillatory index, NOI

The standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples. The test is performed on urine samples that require no processing at the site of collection and without target sequencing or amplification. We sought to verify that the pre-defined KIT test, KIT Score, and clinical thresholds correlate with established chronic kidney disease (CKD) and may provide predictive information of early kidney injury status above and beyond proteinuria and renal function measurements alone. Statistical analyses across six DNA, protein, and metabolite markers were performed on a subset of residual spot urine samples with CKD that met assay performance quality controls from patients attending the clinical labs at the University of California, San Francisco (UCSF) as part of an ongoing IRB approved prospective study. Inclusion criteria included selection of patients with confirmed CKD and normal healthy controls; exclusion criteria included incomplete or missing information for sample classification, logistical delays in transport/processing of urine samples or low sample volume, and acute kidney injury. Multivariate logistic regression of kidney injury status and likelihood ratio statistics were used to assess the contribution of the KIT Score for prediction of kidney injury status and stage of CKD as well as assess the potential contribution of the KIT Score for detection of early stage CKD above and beyond traditional measures of renal function. Urine samples were processed by a proprietary immunoprobe for measuring cfDNA, methylated cfDNA, clusterin, CXCL10, total protein, and creatinine. The KIT Score and stratified KIT Score Risk Group (High versus Low) had a sensitivity and specificity for detection of kidney injury status (healthy or CKD) of 97.3% (95% CI: 94.6%–99.3%) and 94.1% (95% CI: 82.3%–100%). In addition, in patients with normal renal function [eGFR ≥ 90], the KIT Score clearly identifies those with predisposing risk factors for CKD, which could not be picked up by eGFR or proteinuria (p < 0.001). The KIT Score uncovers a burden of kidney injury that may yet be incompletely recognized, opening the door for earlier detection, intervention and preservation of renal function.

Adenine nucleotide (AN) 2^nd messengers such as 3’,5’-cyclic adenosine monophosphate (cAMP) are central elements of intracellular signaling, but many details of underlying processes remain still elusive. Like all nucleotides, cyclic nucleotide monophosphates (cNMPs) are net-negatively charged at physiologic pH which limits their applicability in cell-based settings. Thus, many cellular assays rely on sophisticated techniques like microinjection or electroporation. This setup is not feasible for medium- to high-throughput formats, and the mechanic stress that cells are exposed to raises the probability of interfering artefacts or false-positives. Here, we present a short and flexible chemical route yielding membrane-permeable, bio-reversibly masked cNMPs for which we employed the octanoyloxybenzyl (OB) group. We further show hydrolysis studies on chemical stability and enzymatic activation, and present results of real-time assays, where we used cAMP and Ca²⁺ live cell imaging to demonstrate high permeability and prompt intracellular conversion of some selected masked cNMPs. Consequently, our novel OB-masked cNMPs constitute valuable precursor-tools for non-invasive studies on intracellular signaling.

This paper introduces a novel respiratory detection system based on diaphragm wall motion tracking using an embedded ultrasound sensory system. We assess the utility and accuracy of this method in evaluating diaphragmatic function and its contribution to respiratory workload. The developed system is able to monitor the diaphragm wall activities when the sensor is placed in the zone of apposition (ZOA). This system allows the direct measurements with only one ultrasound PZT5 piezo transducer. The system both generates pulsed ultrasound waves at 2.2 MHz and amplifies reflected echoes. According to the diaphragmatic motions, the respiratory signals of the proposed system is insensitive to human motion artifacts. Promising results were obtained from six subjects on six different tests with an average sensitivity and specificity of 84% and 93% of respiration detection, respectively. Measurements are referenced to a SPR-BTA commercial spirometer. In this study, we also evaluated inertial and photoplethysmography (PPG) sensors as other conventional methods in this area.

As one of the typical deposits in Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province, the Daliangzi Pb-Zn deposit has a close genetic relation with the structural system of “black/fracture zone” formed under the action of NWW-approx. EW strike-slip structures in the metallogenic province, but the mechanism of rock and ore-controlling action of the structural system remains unclear. Based on detailed analysis of tectonite-mineralized alteration lithofacies of R1 “black/fracture zone”, the tectonite-mineralized alteration lithofacies zones can be divided into 4 types in succession outward from the Pb-Zn mineralization center, i.e., ① brecciated and stockwork-like Pb-Zn mineralization-complex breccia facies zone, ② stockwork-like Pb-Zn mineralization-simple breccia and cataclasite facies zone, ③ veined pyrite-sulfide-dolomitic cataclasite facies zone, and ④ fine-veined calcite-black carbonized dolomite facies zone; Cl- and SO42--rich high-temperature oxidizing ore-bearing fluid mixes with reducing fluid in Zone ① while migration and precipitation occur in Zone ④. With the evolution of ore-forming fluid, the homogenization temperature decreases from Zone ① to Zone ④, the salinity increases from Zone ① to Zone ② and then decreases to Zones ③ and ④, and the fluid density has little change on the whole; the contents of Zn, Pb, Cu, Ga, Ge, Cd, Ag, and other metallogenic elements, the Zn/Pb ratio, and the CaO/MgO mole ratio decrease gradually from Zone ① to Zone ④; and REE fractionation, calcilization, silicification, and pyritization enhance gradually from Zone ① to Zone ④. This series of changes are the product of diapirism (cryptoexplosion) of strike-slip structures and “black/fracture zone”, among which the second-order structures (F5, F100, and other faults) derived from NWW-approx. EW striking dextral shear-tension faults F1 and F15 control the brecciated and stockwork-like Pb-Zn mineralized complex breccia facies zones and the stockwork-like Pb-Zn mineralized simple breccia and cataclasite facies zones. Therefore, this paper establishes the zoning mode of tectonite-mineralized alteration lithofacies of “black/fracture zone” and proposes that Zones ① and ② are important prospecting criteria. conclusions.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Precipitation processes are technologies commonly used in hydrometallurgical plants to recover metals or to treat wastewaters. Moreover, solid-liquid separation technologies, such as thickening or filtering, are relevant unit operations, included in the precipitation technologies. These methods are strongly dependent on the characteristics of the solid precipitates formed during the specific precipitation reaction. One of these characteristics is the particle size distribution (PSD) of the solid precipitates which are fed into a solid-liquid separation process. Therefore, PSD determination is a typical practice for the characterization of the slurries generated in a precipitation plant. Furthermore, the precipitates generated in these processes have a colloidal or aggregation behavior, depending on the operational conditions. Nevertheless, the conventional methods used to estimate PSD (e.g., laser diffraction and/or ciclosizer) have not been designed to measure particles that tend to aggregate or disaggregate, since they include external forces (e.g., centrifugal, agitation, pumping and sonication). These forces affect the true size of the aggregates formed in a unit operation, thereby losing representativity in terms of aggregates particle size. This study presents an alternative method of measuring the size distribution of particles with aggregation behavior, particularly, by using non-invasive microscopy and image processing and analysis. The samples used have been obtained from an experimental precipitation process by applying sulfidization to treat the cyanide-copper complexes contained in a cyanidation solution. This method has been validated with statistical tools and compared with a conventional analysis based on laser diffraction. Our results show significant differences between the methods analyzed, demonstrating that image processing and analysis by microscopy is an excellent and non-invasive alternative to obtaining size distribution of aggregates in precipitation processes.

The Universe is treated as an unbound thermodynamic system in which two forces of Nature compete: Attractive gravity loss and repulsive entropic gain. Entropic gain, although not presently considered a force of Nature, is otherwise well known and can be expressed with the gas laws. The Universe at the time of last scattering was all gas. Its instant gain is expressed as gas pressure. When the Gibbs equation is properly applied to this unbound gas, the resulting atomic Hubble parameter is found to be exclusively dependent on baryon density, giving a constant and perpetual two-to-one gain/loss ratio. Instant loss to gravity cannot offset gas pressure in this “thermal equation”. By contrast, the Friedmann equation, a ΛCDM foundation, treats baryon mass as accreted, having little if any entropic gain. These two equations are actually equivalent. Expanding accreted matter at its comoving critical density is herein shown to behave exactly like a freely expanding gas. However, neither equation includes all of today’s Universal kinetic energy, and cannot by themselves fully account for observed stellar movement. The present paper proposes the plausible existence of highly energetic or “suprathermal” free electrons which comprise about half of the intergalactic medium’s kinetic total. It is this suprathermal energy which Λ expresses. The fluid equation, another ΛCDM foundation, eliminates entropic gain from the Gibbs equation. Additionally, rest mass’s Einstein energy E=Mc² is treated as a thermal variable. These two assumptions, isoentropy and energy conflation, led astronomers to populate Λ as they followed the prior art.

Low-intensity noisy galvanic vestibular stimulation (nGVS) can improve static and dynamic postural deficits in patients with bilateral vestibular loss (BVL). In this study, we aimed to explore the neurophysiological and neuroanatomical substrates underlying nGVS treatment effects in a rat model of BVL. Regional brain activation patterns and behavioral responses to repeated 30-min nGVS treatment in comparison to sham stimulation were investigated by serial whole-brain [18F]-FDG-PET measurements and quantitative locomotor assessments before and at 9 consecutive time points up to 60 days after chemical bilateral labyrinthectomy (BL). [18F]-FDG-PET revealed a broad nGVS-induced modulation on regional brain activation patterns encompassing biologically plausible brain networks in the brainstem, cerebellum, multisensory cortex and basal ganglia during the entire observation period post-BL. nGVS broadly reversed brain activity adaptions occurring in the natural course post-BL. Parallel behavioral locomotor assessment demonstrated a beneficial treatment effect of nGVS on sensory-ataxic gait alterations, particularly in the early stage of post-BL recovery. Stimulation-induced locomotor improvements were finally linked to nGVS brain activity responses in the brainstem, hemispheric motor and limbic networks. In conclusion, combined [18F]-FDG-PET and locomotor analysis discloses the potential neurophysiological and neuroanatomical substrates that mediate previously observed therapeutic nGVS effects on postural deficits in patients with BVL.

The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.

We derive time evolution equations, namely the Schrodinger-like equations and the Klein-Gordon equations for coherent fields and the Kadanoff-Baym (KB) equations for quantum fluctuations, in Quantum Electrodynamics (QED) with electric dipoles in 2 + 1 dimensions. Next we introduce a kinetic entropy current based on the KB equations in the 1st order of the gradient expansion. We show the H-theorem for the Leading-Order self-energy in the coupling expansion (the Hartree-Fock approximation). We show a conserved energy in the spatially homogeneous systems in the time evolution. We derive aspects of the super-radiance and the equilibration in our single Lagrangian. Our analysis can be applied to Quantum Brain Dynamics, that is QED with water electric dipoles. The total energy consumption to maintain super-radiant states in microtubules seems to be within the energy consumption to maintain the ordered systems in a brain.

Diabetes mellitus is a widespread chronic metabolic disorder demanding regular blood glucose level surveillance (BGLs). Current invasive techniques, such as finger-prick tests, often result in discomfort for patients, leading to infrequent monitoring and potential health complications. The primary objective of this study was to design a novel, portable, non-invasive system for diabetes detection using breath samples, named as DiabeticSense, an affordable digital health device for early detection, encouraging immediate intervention. The device employed MOSFET-based electrochemical sensors to assess volatile organic compounds in breath samples, whose concentrations differ between diabetic and non-diabetic individuals. The system merged body vital signs with sensor voltages obtained by processing breath sample data to predict diabetic conditions. Our research used readings from 100 patients at a nationally recognised hospital to form the dataset. Data was then processed 10 using a Gradient Boosting Classifier model, and performance was cross-validated. The proposed system attained a promising accuracy of 86.6%, marking an improvement of 20.72% over an existing regression technique. The developed device introduces a non-invasive, cost-effective, and user-friendly solution for preliminary diabetes detection. It has the potential to increase patient adherence to regular monitoring.

In order to enable patients with severe disabilities who have lost their limbs to accurately control their wheelchair movement and optimize the power loss of smart wearable tongue control devices, a non-invasive intraoral stand-alone tongue control system based on RSIC-V edge computing is proposed in this paper. Patients can detect the pressure signal of the tongue muscles’ touching the palate by placing the flexible carbon nanotube-PDMS pressure sensor array in the mouth, and the erroneous movement signal can be avoided by setting the pressure threshold, thereby improving the reliability of the device and the user's experience. The system converts the pressure data into specific control instructions on the edge of the RSIC-V chip and transmits them to the receiver, thus reducing the transmission of data. In this experiment, the speed response time test, the center click task and the power consumption experiment are carried out, whose results show that the adaptive fuzzy PID control algorithm has good robustness in the system: when the DC motor with a given speed of 750r/min reaches the steady state, its rise time is 0.108s and the adjustment time is 0.59s. The dynamic power consumption of the non-intrusive intraoral stand-alone tongue control system proposed in this paper is tested to be 3.745 MW, which is 11.5% lower than the total power consumption of the sTDs system.

In this paper, we introduce a non-invasive approach for monitoring bridge infrastructure with ground-based interferometric radar. This approach is called the mirror mode, since it utilises the flat surface of the bridge underside as a mirror to reflect the signal to a corner reflector on the ground placed opposite of the radar sensor. For proving the feasibility of this approach, a measurement campaign has been carried out at an exemplary bridge in Karlsruhe (Germany) including a radar sensor in mirror mode, a second radar sensor in the default mode and a laser profile scanner. We investigate the potential of this approach to monitor the bridge displacement in vertical direction and compare the results with the two other sensors. The derived results reveal the potential for monitoring bridge infrastructure. Finally, we propose further research aspects of this approach to analyse its capabilities and limitation in the context of non-invasive infrastructure monitoring.

The chicken embryo is a widely used experimental animal-model in many studies such as developmental biology and to study the physiological responses and adaptation to altered environments as well as for cancer and neurobiology research. Embryonic heart rate is an important physiological variable useful as an index reflecting the embryo's natural activity and is considered one of the most difficult parameters to measure. An acceptable measurement technique of embryonic heart rate should provide a reliable cardiac signal quality while maintaining adequate gas exchange through the eggshell along the incubation and embryonic developmental period. In this paper, we presented a detailed design and methodology for a non-invasive PPG-based prototype (Egg-PPG) for real-time and continuous monitoring of embryonic heart rate during incubation. An automatic embryonic cardiac wave detection algorithm, based on normalised spectral entropy, is described. The developed algorithm successfully estimated the embryonic heart rate with 98.7% accuracy. We believe that the developed overall system presented in this paper is showing a promising solution for non-invasion, real-time monitoring of embryonic cardiac signal, which can be used in both experimental studies (e.g., developmental embryology and cardiovascular research) and in industrial incubation applications.

The Dutch Konik is valued from a genetic conservation perspective and also for its role in preservation of natural landscapes. The primary management objective for the captive breeding of this primitive horse is to maintain its genetic purity, whilst also maintaining the nature reserves on which they graze. Breeding selection has traditionally been based on phenotypic characteristics consistent with the breed description, and the selection of animals for removal from the breeding program is problematic at times due to high uniformity within the breed. With the objective of identifying an additional non-invasive selection criterion with potential uniqueness to the Dutch Konik, this study investigates the anatomic parameters of the distal equine limb, with a specific focus on the relative lengths of the individual splint bones. Post-mortem dissections performed on distal limbs of Dutch Konik (n = 47) and modern domesticated horses (n = 120) revealed significant differences in relation to the length and symmetry of the 2nd and 4th Metacarpals and Metatarsals. Distal limb characteristics with apparent uniqueness to the Dutch Konik are described which could be an important tool in the selection and preservation of the breed.

Purpose: Dysarthria, a neurological injury of the motor component of the speech circuitry, is of common consequences of traumatic brain injury (TBI). Palilalia is a speech disorder characterized by involuntary repetition of words, phrases, or sentences. Based on the evidence supporting the effectiveness of transcranial direct current stimulation (tDCS) in some speech and language disorders, we hypothesized that using tDCS would enhances the effectiveness of speech therapy in a client with chronic dysarthria following TBI. Method: We applied the constructs of the “Be Clear” protocol, a relatively new approach in speech therapy in dysarthria, together with tDCS on a chronic subject who affected by dysarthria and palilalia after TBI. Since there was no research on the use of tDCS in such cases, regions of interest (ROIs) were identified based on deviant brain electrophysiological patterns in speech tasks and resting state compared with normal expected patterns using the Quantitative Electroencephalography (QEEG) analysis. Results: Measures of perceptual assessments of intelligibility, an important index in the assessment of dysarthria, ​​were superior to the primary protocol results immediately and 4 months after intervention. We did not find any factor other than the use of tDCS to justify this superiority. The percentage of repeated words, an index in palilalia assessment, had a remarkable improvement immediately after intervention but fell somewhat after 4 months. We justified this case with subcortical origins of palilalia. Conclusion: Our present case-based findings suggested that applying tDCS together with speech therapy may improve intelligibility in similar case profiles as compared to traditional speech therapy. To reconfirm the effectiveness of the above approach in cases with dysarthria following TBI, more investigation need to be pursued.

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM), is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and with aggressive in the clinic. Thus, it’s important to select a proper drug to block tumor cell migration for clinic treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a more ideal candidate for inhibition of NCAM polysialylation comparing with CMP and low molecular weight heparin (LMWH), which were determined based on our NMR studies. On the other hand, because neutrophil extracellular traps (NET) is the most dramatic stage in cell death process, and NETs’ release are related to pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis and vascular disorders. In this study, the molecular mechanism of inhibition of NETs’ release using LFcinB11 as inhibitor was also determined. Based on these results, LFcinB11 is proposed to be bifunctional inhibitor for inhibiting both NCAM polysialylation and NETs releases.

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodelling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to “compute” the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions.Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodelling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events.From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

In recent years, advancements in brain science and neuroscience have significantly influenced the field of computer science, particularly in the domain of reinforcement learning (RL). Drawing insights from neurobiology and neuropsychology, researchers have leveraged these findings to develop novel mechanisms for understanding intelligent decision-making processes in the brain. Concurrently, the emergence of quantum computing has opened new frontiers in artificial intelligence, leading to the development of quantum machine learning (QML). This study introduces a novel model that integrates Quantum Spiking Neural Networks (QSNN) and Quantum Long Short-Term Memory (QLSTM) architectures, inspired by the complex workings of the human brain. Specifically designed for reinforcement learning tasks in energy-efficient environments, our approach progresses through two distinct stages mirroring sensory and memory systems. In the initial stage, analogous to the brain’s hypothalamus, low-level information is extracted to emulate sensory data processing patterns. Subsequently, resembling the hippocampus, this information is processed at a higher level, capturing and memorizing correlated patterns. We conduct a comparative analysis of our model against existing quantum models such as Quantum Neural Networks and their classical counterparts, elucidating its unique contributions. Through empirical results, we aim to underscore the effectiveness of our approach in optimizing energy consumption in practical scenarios.

Until recently, no disease-specific health-related quality of life (HRQoL) instrument existed for pediatric traumatic brain injury (TBI). In this revalidation study, the psychometric properties and the validity of the final German version of the 35-item QOLIBRI-KID/ADO questionnaire were examined in 300 children and adolescents. It is the first self-reported TBI-specific instrument for measuring pediatric HRQoL in individuals aged 8–17 years. The six-factor model fits the data adequately. Internal consistencies were excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability. Construct validity was supported by overlaps between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. Discriminant validity indicated that HRQoL was significantly lower in older children and girls, and in those with anxiety, depression, and post-concussion symptoms than in comparison groups, replicating the results of the questionnaire’s first development study. Our results suggest that the QOLIBRI-KID/ADO is a valid and reliable multidimensional instrument for assessing disease-specific HRQoL after pediatric TBI in clinical and research settings, which can additionally be used across the lifespan in combination with the adult version. This may help to improve care, treatment, daily functioning and HRQoL after TBI.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

Advanced glycation end products (AGEs) play a significant role in the aging processes, further regarding as a hallmark of aging. Despite the importance, a lack of monitoring tools has hampered the study of relationship between AGEs and aging. Here, we firstly report a novel AGEs-selective probe, AGO. AGO presented its ability to detect AGEs more sensitively than a conventional approach of measuring autofluorescence from AGEs. In addition, we confirmed that AGO can detect AGEs depending on kinetics, reflecting by a preference to ribose-derived AGEs. Finally, AGO revealed its competence to visualize glycation products in glycation mimicking model, made by collagen framework. We believe that this study will enrich molecular toolboxes to understand physiological processes of AGEs during aging processes.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

Perinatal brain injury is a major public health problem burdened with high morbidity, mortality and severe neurological sequelae. Despite advances in neonatal life-saving technologies, neonatal encephalopathy lacks specific and effective treatment. Therefore, mechanisms of central nervous system changes associated with perinatal brain injury have been a hot topic of neonatology research. In recent years, researchers have shifted more focus from neurons themselves to perineuronal cells and intercellular interactions. As a member of the nervous system network, astrocytes are one of the dominant glial cells that regulate ion homeostasis, blood flow, and antioxidant function in the brain. Their changes in molecular mechanisms (e.g., alterations in RNA regulatory networks) during brain injury storms deserve further attention. Non-coding RNAs participate in and promote reactive pathophysiologic changes in astrocytes. The review summarizes and discusses the role of non-coding RNAs in astrocytes in recent years in studies of neonatal brain injury. It focuses on the most studied disease-related ncRNAs: miRNAs, lncRNAs and circRNAs, and hopes to provide possible directions for pathophysiological studies and therapeutic approaches of neonatal brain injury.

Alzheimer's disease (AD) is an incurable neurodegenerative disorder. Early screening, particularly in blood has been regarded as an effective approach for AD diagnosis and prevention. In addition, metabolic dysfunction has been demonstrated to be closely related to AD, which might be reflected in whole blood transcriptome. Hence, we hypothesized that establishment of diagnostic model based on metabolic signatures of blood is a workable strategy. To the end, we initially constructed metabolic pathway pairwise (MPP) signatures to characterize the interplay among metabolic pathways. Then, a series of bioinformatic methodologies, e.g., differential expression analysis, functional enrichment analysis, and network analysis, etc. were used to investigate the molecular mechanism behind AD. Moreover, an unsupervised clustering analysis based on the MPP signature profile via Non-Negative Matrix Factorization (NMF) algorithm was utilized to stratify AD patients. Finally, aimed at distinguishing AD patients from non-AD group, a metabolic pathway-pairwise scoring system (MPPSS) was established using multi-machine learning methods. As a result, many metabolic pathways correlated to AD were disclosed, including oxidative phosphorylation and fatty acid biosynthesis, etc. NMF clustering analysis divided AD patients into two subgroups (S1 and S2), which exhibit distinct activities of metabolism and immunity. Typically, oxidative phosphorylation in S2 exhibits a lower activity than that in S1 and non-AD group, suggesting the patients in S2 might possess a more compromised brain metabolism. Additionally, Immune infiltration analysis showed that the patients in S2 might have phenomena of immune suppression, compared with S1 and non-AD group. These findings indicated that S2 probably have a more severe progression of AD. Finally, MPPSS could achieve an AUC of 0.73 in training dataset, 0.71 in testing dataset and an AUC of 0.82 on weighted average in five external validation datasets. Overall, our study successfully established a novel metabolism-based scoring system for AD diagnosis using blood transcriptome, and provided new insight into the molecular mechanism of metabolic dysfunction implicated in AD.

Reflected light carries ample information about biochemical composition, tissue architecture, and physiological condition of plants. Recent technical progress brought about affordable imaging hyperspectrometers (IH) providing spatially resolved spectral data on plants. The extraction of sensible information from hyperspectral reflectance images is difficult due to inherent complexity of plant tissue and canopy optics, especially when recorded by IH under ambient sunlight. We aimed at obtaining a deeper insight into plant optics as perceived by IH since there is a high demand for algorithms for fruit harvesting and grading systems equipped with computer vision and robotic systems capable of working in orchard. We report on the characteristic changes in hyperspectral reflectance accompanying the accumulation of anthocyanins in healthy fruit, pigment breakdown during sunscald and phytopathogen attacks. The measurements made outdoors with a snapshot IH were compared with traditional “point” reflectance measured with a conventional spectrophotometer under controlled illumination conditions. Most of the spectral features and patterns of plant reflectance were evident in the IH-derived reflectance images. As a step forward, a novel index for highlighting tissue damages on the background of the anthocyanin absorption, BRI-M = (1/Rorange – 1/Rred + 1/RNIR), is suggested. Difficulties of the interpretation of fruit hyperspectral reflectance images recorded in situ are discussed with possible implications for plant physiology and precision horticulture practices.

Dermal water content is an important biophysical parameter in preserving skin integrity and preventing skin damage. Traditional electrical-based and open-chamber evaporimeters have several well-known limitations. In particular, such devices are costly, sizeable, and only provide arbitrary outputs. They also do not permit continuous and non-invasive monitoring of dermal water content, which can be beneficial for various consumer, clinical and cosmetic purposes. We report here on the design and development of a digital multi-wavelength optical sensor that performs continuous and non-invasive measurement of dermal water content. In-silico investigation on porcine skin was carried out using the Monte Carlo modelling strategy to evaluate the feasibility and characterise the sensor. Subsequently, an in-vitro experiment was carried out to evaluate the performance of the sensor and benchmark its accuracy against a high-end, broad band spectrophotometer. Reference measurements were made against gravimetric analysis. The results demonstrate that the developed sensor can deliver accurate, continuous, and non-invasive measurement of skin hydration through measurement of dermal water content. Remarkably, the novel design of the sensor exceeded the performance of the high-end spectrophotometer due to the important denoising effects of temporal averaging. The authors believe, in addition to wellbeing and skin health monitoring, the designed sensor can particularly facilitate disease management in patients presenting diabetes mellitus, hypothyroidism, malnutrition, and atopic dermatitis.

Objective: To investigate whether impaired plantar cutaneous vibration perception contributes to axial motor symptoms in Parkinson’s disease (PD) and whether anti-parkinsonian medication and subthalamic nucleus deep brain stimulation (STN-DBS), show different effects. Methods: Three groups were tested: PD patients on medication (PD-MED), PD patients on medication and additional STN-DBS (PD-MED–DBS), and healthy subjects (HS) as reference. Motor performance was analyzed using a pressure distribution platform. Plantar cutaneous vibration perception thresholds (VPT) were investigated using a customized vibration exciter at 30 Hz. Results: Motor performance of PD-MED and PD-MED–DBS was characterized by greater postural sway, smaller limits of stability ranges, and slower gait, due to shorter strides, fewer steps per minute, and broader stride widths compared to HS. Comparing patient groups, PD-MED–DBS showed better overall motor performance than PD-MED, particularly for the functional limits of stability and gait. VPTs were significantly higher for PD-MED compared to HS, which suggests impaired plantar cutaneous vibration perception in PD. However, PD-MED–DBS showed less impaired cutaneous vibration perception than PD-MED. Conclusion: PD patients suffer from poor motor performance compared to healthy subjects. Anti-parkinsonian medication in conjunction with STN-DBS seems to be superior for normalizing axial motor symptoms compared to medication alone. Plantar cutaneous vibration perception is impaired in PD patients, whereas anti-parkinsonian medication together with STN-DBS is superior for normalizing tactile cutaneous perception compared to medication alone. Consequently, based on our results and the findings of the literature impaired plantar cutaneous vibration perception might contribute to axial motor symptoms in PD.

Mammalian genomes encode tens of thousands of long-noncoding RNAs (lncRNAs), which are capable of interactions with DNA, RNA and protein molecules, thereby enabling a variety of transcriptional and post-transcriptional regulatory activities. Strikingly, about 40% of lncRNAs are expressed specifically in the brain in precisely regulated temporal and spatial expression patterns. In stark contrast to the highly conserved repertoire of protein-coding genes, thousands of new lncRNAs have appeared during primate nervous system evolution with hundreds of human-specific lncRNAs. Their evolvable nature and the myriad of potential functions make lncRNAs ideal candidates for drivers of human brain evolution. The human brain displays the largest relative volume of any animal species and the most remarkable cognitive abilities. In addition to brain size, structural reorganization and adaptive changes represent crucial hallmarks of human brain evolution. LncRNAs are increasingly reported to be involved in neurodevelopmental processes including proliferation, neurite outgrowth and synaptogenesis, as well as in neuroplasticity, suggested to underlie human brain evolution. Hence, evolutionary human brain adaptations are proposed to be essentially driven by lncRNAs, which will be discussed in this review.

In our country, the aging society is rapidly progressing, with an increase in patients with chronic kidney disease (CKD) and those undergoing dialysis, coupled with the aging of the population. As a result, the number of individuals with cognitive impairment (CI) is rising, and addressing this issue has become an urgent problem. One characteristic of dementia in CKD patients is the high frequency of vascular dementia, making the prevention through the management of classical risk factors such as hypertension, diabetes mellitus, dyslipidemia, smoking, etc., associated with atherosclerosis and arteriosclerosis. Other effective measures, including the use of renin-angiotensin system inhibitors, addressing anemia, exercise therapy, and lifestyle improvements, have been reported. Incidence and progression of CI may also be influenced by the type of dialysis or kidney replacement therapy, with reports suggesting that long-duration dialysis, low-temperature hemodialysis, peritoneal dialysis, and kidney transplantation (KTx) can have a possible preferable effect on preserving cognitive function.

Electrical transmission between neurons is largely mediated by gap junctions. These junctions allow the direct flow of electric current between neurons, and in mammals are mostly composed of the protein connexin (Cx)36. Circuits of electrically coupled neurons are widespread in these animals, plus, experimental and theoretical evidence supports the notion that, beyond synchronicity, these circuits are able to perform sophisticated operations like lateral excitation and inhibition, noise reduction, as well as the ability to selectively respond upon coincident excitatory inputs. Although once considered stereotyped and unmodifiable, we now know that electrical synapses are subject to modulation and, by reconfiguring neural circuits, these modulations can alter relevant operations. The strength of electrical synapses depends on gap junction conductance, as well as on its functional interaction with the electrophysiological properties of coupled neurons. In particular, voltage dependent channels of the non-synaptic membrane critically determine the efficacy of transmission at these contacts. Consistently, modulatory actions on these channels have been shown to represent relevant mechanisms of plasticity of electrical synaptic transmission. Here we review recent evidence on the regulation of electrical synapses of mammals, the underlying molecular mechanisms, and the possible ways in which they affect circuit function.

Introduction: The objective of the study is to assess the failure of therapies with HFNO (High-Flow Nasal Oxygen), CPAP, Bilevel or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. Methods: Retrospective and observational study of SARS-CoV-2 positive patients who required non-invasive respiratory support (NIRS), at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. Results: Of 7355 patients, 197 (11,8%) were included. 95 of them failed this therapy (48,3%). We objectivated that during hospitalization in the ward the combined therapy with HFNO and CPAP had a lower failure rate overall and the highest treatment purely with Bilevel (p = 0,005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP and combined therapy of HFNO with CPAP, (35,6% of patients) presented a 24,2% failure compared to those who did have two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64,4% of patients) with 75,8% associated failure (OR: 0, 374; CI 95%: 0,203-0,688. p=0,001).Conclusions: The use of NIRS in conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy with Bilevel increases the probability of failure, with the combined therapy strategy with CPAP and HFNO being the most promising option.

Salmonella, especially invasive non-typhoidal Salmonella (iNTS) are responsible for developing various invasive diseases, and possess higher mortality rate, due to their higher antibiotic resistance profile than the other bacteria. Therefore, the present study was concerned to develop epitope based peptide vaccine against iNTS species as a successive and substitute protective measures. The study considered comprehensive Immunoinformatic approaches, followed by molecular docking and molecular dynamics simulation to predict the efficient vaccine candidate T cell and B cell epitopes, based on the outer membrane proteins. The study identified two best epitopes YGIFAITAL and KVLYGIFAI from total iNTS outer membrane proteins, which showed higher immunity, non-allergenicity, non-toxicity and also showed higher conservancy and population coverage values. Both epitopes showed higher binding affinity and stability towards HLA-C* 03:03. The MM-PBSA binding free energy showed the YGIFAITAL epitope binds more tightly with both MHC-I and MHC-II molecules. The total contact, H-bond analysis and RMSF results also validate the efficiency of these epitopes as vaccine candidate. The projected B cell epitopes AAPVQVGEAAGS, TGGGDGSNT and TGGGDGSNTGTTTT showed higher antigenicity. Overall, the study concluded that these epitopes can be considered as the potential vaccine candidate to make a successive vaccine against iNTS species. However, this result further needs to be validate by wet lab research to make successive vaccine with these projected epitopes.

This paper discusses a cross-disciplinary, international collaboration aimed at researching a series of 15th century choir books at the abbey of San Giorgio Maggiore on the homonymous island in Venice. Produced for the abbey itself, the books have never left the island during their 500-years history, thereby allowing a unique opportunity to analyse historic artefacts, which have undergone little modification over time. Prompted by ongoing cataloguing work on the manuscripts, a week-long analytical campaign using a combination of non-invasive analytical methods used in portable configuration allowed the comprehensive characterisation of ten volumes. The manuscripts’ palette and painting techniques were analysed using near-infrared imaging, reflectance spectroscopy in the UV-vis-NIR range, Raman spectroscopy, X-ray fluorescence mapping and digital microscopy. The paper will discuss the challenges linked to the fragility and the large dimensions of the volumes as well as the most interesting results of the investigation. These include the detection of unusual painting materials such as bismuth ink, as well as the discovery of a less homogeneous palette than originally expected, which prompted a partial revision of the attribution of the decoration in one of the volumes to a single artist.

The reasons for the circular sense of human color perception generated by two sorts of color opponent neurons and three cone types are not well understood. Here we use geometrical analysis to examine the hypothesis that opponency, the recursive nature of color perception, and trichromacy arise as the most efficient ways of distinguishing spectrally different points on a plane using a minimum of color classes and receptor types.

Three-phase motors are commonly adopted in several industrial contexts and their failures can result in costly downtime causing undesired service outages; this way, motor diagnostics is an issue that assumes great importance. To prevent their failures and timely face the considered service outages, a non-invasive method to identify electrical and mechanical faults in three-phase asynchronous electric motors is proposed in the paper. In particular, a measurement strategy along with a machine learning algorithm based on Artificial Neural Network is exploited to properly classify failures. In particular, digitized current samples of each motor phase are first processed by means of FFT and PSD in order to estimate the associated spectrum. Suitable features (in terms of frequency and amplitude of the spectral components) are then singled out to either train or feed a neural network acting as a classifier. The method is preliminary validated on a set of 28 electric motors, and its performance is compared with common state-of-art machine learning techniques. The obtained results show that the proposed methodology is able to reach accuracy levels greater than 98\% in identifying anomalous conditions of three-phase asynchronous motors.

We compared two approaches to non-invasive proximal sensing of the early changes in fresh-cut lettuce leaf quality: hyperspectral imaging and imaging PAM-fluorometry of chlorophyll contained in the leaves. The assessments made by the imaging techniques were confronted with the quality assessments made by traditional biochemical assays: relative water content and foliar pigment (chlorophyll and carotenoid) composition. The hyperspectral imaging-based approach provided the highest sensitivity to the decline of fresh-cut lettuce leaf quality taking place within 24 h from cutting. Using of the imaging PAM was complicated by (i) weak correlation of the spatial distribution pattern of the Qy parameter with the actual physiological condition of the plant object and (ii) its high degree of heterogeneity. Accordingly, the imaging PAM-based approach was sensitive only to the manifestations of leaf quality degradation only at advanced stages of the process. Sealing the leaves in the polyethylene bags slowed down the leaf quality degradation at the initial stages (&lt; 3 days) but promoted its rate at more advanced stages, likely due to build-up of ethylene in the bags. An approach was developed to the processing of hyperspectral data for non-invasive monitoring of the lettuce leaves with a potential for implementation in greenhouses and packinghouses.

Bio-absorbable stents are a novel tool which relieve stenosis and then resorb as the patient grows, avoiding obligatory re-intervention. This case describes the novel use of an iron bio-absorbable stent in a child with surgically repaired Tetralogy of Fallot who post-operatively developed a severely stenotic right ventricular outflow tract.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

Arrhythmic sudden cardiac death (SCD) has an annual prevalence of 1 per 1000 while 75% of the victims suffer from ischemic and 10% from non-ischemic or hypertrophic cardiomyopathy. Altogether, these three entities account for more than 80% of the total SCD victims. Guidelines for implantable cardiac defibrillators are still dominated by LVEF<30% from the MADIT II study. In terms of arrhythmic risk stratification, the PRESERVE-EF study restored in clinical practice the two-step arrhythmic risk stratification approach based on Electrocardiographic non-invasive risk factors (NIRFs) guiding to electrophysiological study. In our times with the multiple cardiac imaging methods and artificial intelligence applications availability, this two-step approach based on integrated arrhythmia mechanisms detection, emerges as an efficient SCD risk stratification paradigm for these three entities but also for the patients with congenital heart disease.

Surgical methods for treating spasmodic torticollis include denervation and myotomy (DAM) of the affected muscles, and deep brain stimulation (DBS). This study reports on the long-term efficacy, prognostic factors, safety, and hospitalization costs following these two procedures. We collected data from 94 patients with spasmodic torticollis, of whom 41 and 53 were treated with DAM and DBS, respectively, from June 2008 to December 2020 at the Chinese People’s Liberation Army General Hospital. We used the Tsui scale and the global outcome score of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) to evaluate the preoperative and postoperative clinical condition in all patients. We also determined the cost of hospitalization, prognostic factors, and serious adverse events following the two surgical procedures. The mean follow-up time was 68.83 months (range = 13–116). Both resection surgery and DBS showed good results in terms of Tsui (Z = -5.103, P = 0.000; Z = -6.210, P = 0.000) and TWSTRS scores (t = 8.762, P = 0.000; Z = -6.308, P = 0.000). Compared with the DAM group, the preoperative (47.71, range 24–67.25) and postoperative (18.57, range 0–53) TWSTRS scores in the DBS group were significantly higher (Z = -3.161, P = 0.002). We found no correlation between prognostic factors and the patient age, gender, or disease duration for either surgical procedure. However, prognostic factors were related to the length of the postoperative follow-up period in the DBS surgery group (Z = -2.068, P = 0.039; Z = -3.287, P = 0.001). The mean hospitalization cost in the DBS group was 6.85 times that found in the resection group (Z = -8.284, P = 0.000). The total complication rate was 4.26%. We found, both resection surgery and DBS, showed good results in the patients with spasmodic torticollis. Although DBS had a greater impact on the quality of life and the degree of pain relief, it was more expensive. Prognostic factors were related to the length of the postoperative follow-up period in patients who underwent DBS surgery.