Besides common skin pathogens, acute focal lymphadenitis in humans can be caused by a zoonotic pathogen in rare cases. Furthermore, it can develop in absence of any direct or indirect contact with infected animal in cases when the microorganism is transmitted by vector. This clinical entity is rare, and therefore not easily recognized in most regions, yet many zoonotic illnesses are considered emerging or re-emerging nowadays. Focal zoonotic vector-borne lymphadenitis and its numerous causative agents with their variegated clinical manifestations have been described in some case reports and small case series. Therefore, we tried to summarize those data in this narrative overview, with the aim to rise clinical awareness, which could improve clinical outcomes. This overview briefly covers reported pathogens, their vectors and geographic distribution, as well as their main clinical manifestations, diagnostic possibilities and recommended therapy. Vector-borne tularemia, plague, bartonellosis, rickettsioses, borreliosis and Malayan filariasis are mentioned. According to the existing data, when acute focal bacterial vector-borne zoonotic lymphadenitis is suspected, in severe or complicated cases it seems prudent to apply combined aminoglycoside (or quinolone) plus doxycycline as an empirical therapy, pending definite diagnostic results. In this field the „one health approach” and further epidemiological and clinical studies are needed.

The straight leg raise test (SLR) has been proposed to detect increased nerve mechanosensitivity of the lower limbs in individuals with low back pain or leg-related low back pain. However, its validity in the diagnosis of lumbosacral radiculopathy show very variable results. The aim of this study was to analyse the diagnostic validity of the SLR including well defined diagnostic criteria in a sample of participants in phase III with suspicion of lumbar radiculopathy using the nerve conduction studies (NDS) as the reference standard. A phase III diagnostic accuracy study was designed. 142 individuals with suspected lumbosacral radiculopathy referred for NCS participated in the study. Each participant was tested with NCS and SLR. SLR was considered positive using three diagnostic criteria. The sensitivity of the SLR for the criterion 3 was 89.02% (CI 81.65-96.40), the specificity was 25.00% (CI 13.21-36.79), and the +LR and -LR were 1.19 (CI 1.01-1.40) and 0.44 (0.21-0.94), respectively. SLR showed limited validity in the diagnosis of lumbosacral radiculopathy. The incorporation of more objective diagnostic criteria (asymmetry in range of motion or localization of symptoms) improved diagnostic validity but the imprecision of the confidence intervals limited the interpretation of the results.

The purpose of this article is to highlight the new advancements in molecular and diagnostic genetic testing as well as properly classify all ovarian cancers. In this article we address statistics, histopathological classification, molecular pathways implicated in ovarian cancer, genetic screening panels and details about the genes, and also candidate genes. We hope to bring new information in the medical field as to better prevent and diagnose ovarian cancer.

Alternative splicing can produce transcripts that affect cancer development and shows potential for cancer diagnosis and treatment. However, intron retention (IR), a type of alternative splicing, has been less systematically studied in cancer biology research. Here, we generated a pan-cancer IR landscape for more than 10,000 samples across 33 cancer types from The Cancer Genome Atlas (TCGA). We characterized differentially retained introns between tumor and normal samples and identified retained introns associated with survival. We discovered 988 differentially retained introns in 14 cancers, some of which demonstrated diagnostic potential in multiple cancer types. We also inferred a large number of prognosis-related introns in 33 cancer types, and the associated genes included well-known cancer hallmarks such as angiogenesis, metastasis, and DNA mutations. Notably, we discovered a novel intron retention event inside 5′UTR of STN1 that is associated with the survival of lung cancer patients. The retained intron reduces translation efficiency by producing upstream open reading frames (uORFs) and thereby inhibits colony formation and cell migration of lung cancer cells. Besides, the IR-based prognostic model achieved good stratification on certain cancers, as illustrated in acute myeloid leukemia. Taken together, we performed a comprehensive IR survey at a pan-cancer level, and the results implied that IR has the potential to be diagnostic and prognostic cancer biomarkers, as well as new drug targets.

The process industry is confronted with rising demands for flexibility and efficiency. One way to achieve this are modular process plants that consist of pre-manufactured modules with their own decentralized intelligence. Plants are then composed of these modules as unchangeable building blocks and can be easily re-configured for different products. Condition monitoring of such plants is necessary, but available solutions are not applicable. The authors suggest an approach in which model-based symptoms are derived from few measurements and observers that are based on manufacturer knowledge. The comparisons of redundant observers lead to residuals that are classified to obtain symptoms. These symptoms can be communicated to the plant control and are inputs to an easily adaptable diagnosis. The implementation and validation at a modular mixing plant showcases the feasibility and the potential of this approach.

The viral nervous necrosis virus (VNNV) is the causative agent of an important disease affecting fish species cultured worldwide. Early and accurate diagnosis is at present the most effective control and prevention tool, and the molecular techniques have been strongly introduced and accepted by official organizations. Among those, real time quantitative polymerase chain reaction (rt-qPCR) is nowadays displacing other molecular techniques. However, another PCR-based technology, the droplet digital PCR (ddPCR), is on the increase. It has many advantages over qPCR, such as higher sensitivity and more reliability of the quantification. Therefore, we decided to design and validate a protocol for diagnosis and quantification of SJ and RG type VNNV, using reverse transcription-ddPCR (RT-ddPCR). We obtained an extremely low limit of detection, 10 to 100-folds lower than with RT-qPCR. Quantification by RT-ddPCR, with a dynamic range of 6.8 – 6.8 x 104 (SJ type) or 1.04 x 101 – 1.04 x 105 (RG) cps/rctn, was more reliable than with RT-qPCR. The procedure was tested and validated in field samples, providing the high clinical sensitivity and negative predictive values. In conclusion, we propose this method to substitute RT-qPCR protocols because it exceeds the expectations of qPCR in the diagnosis and quantification of VNNV.

Introduction: This study aimed to identify factors associated with late diagnosis and clinically monitor newly diagnosed HIV/AIDS patients. Method: Retrospective longitudinal study, based on secondary data from a specialized unit at a tertiary hospital. Data collection included sociodemographic, behavioral, clinical, and laboratory data of newly diagnosed HIV patients between 2015-2019. Data analysis adopted inferential statistical tests using the SPSS program, considering α ≤ 0.05. Results: 314 individuals were newly diagnosed with HIV/AIDS. 70.3% (208) had a late diagnosis, and 57.1% (169) were diagnosed very late. There was an association of the very late diagnosis with the variables sex and education and with origin, entry, occurrence of opportunistic diseases, use of ARV therapy, and death, associated with late and very late diagnosis, respectively. The results of the regression model indicate that males had 2.28 [95% CI 1.11 - 4.46] higher chances of having a late diagnosis compared to females. Conclusions: This study evidenced a high prevalence of late and very late diagnoses in newly diagnosed male HIV patients who presented with opportunistic diseases, requiring hospitalization, and having a significant risk of progressing to death.

Leptospirosis is a zoonotic disease that has a cosmopolitan geographical distribution, reported in domestic and wild animals, which act as reservoirs and contribute to the spread of the microorganism in the environment. In Brazil, studies on the occurrence of leptospirosis in buffaloes in the Amazon biome are scarce. The objective of this study was to determine the occurrence of antibodies against Leptospira spp., including serovar Hardjo (Bolivia), isolated from cattle in Brazil and not yet tested in buffaloes. A total of 387 blood serum samples of animals from nine municipalities in the Marajó Island, state of Pará, northern Brazil, were obtained from a biological sample bank and analyzed using the serum agglutination microscopic test (SAM). Serology revealed 91.5% (387/354) of the animals tested positive for anti-Leptospira antibodies. Among the serovars tested, the serovar Hardjo (Bolivia) was the most prevalent, present in 79.3% of the reactive buffaloes.

Background: Craniofacial injuries are thought to be commonly associated with traumatic brain injury (TBI), but there is conflicting evidence in the literature. The objective of this retrospective cohort study is to evaluate the incidence of TBI in patients with craniofacial trauma. Methods: The study included 2982 consecutive patients with either solitary or concurrent diagnoses of TBI and facial fractures, seen and evaluated at a single level II trauma center between January 1, 2010 and December 31, 2020. Continuous variables were compared against whether the patient had one or both diagnoses.Results: Of the target population, 55.8% had a solitary diagnosis of TBI, 30.28% had a solitary diagnosis of facial fractures, and 13.92% had concurrent diagnoses of both TBI and facial fractures. Patients with concurrent diagnoses had a significantly longer mean length of stay (LOS) compared to those with solitary diagnoses (9.92 ± 16.33 days vs. 6.21 ± 10.96 days, p<0.01), but age (p=0.68) and ICU LOS (p=0.09) did not differ significantly between the two groups. Conclusions: Trauma to the face should be given special attention due to the close relationship between facial bones and the brain. Patients with concurrent diagnoses of TBI and facial fractures had worse hospital outcomes than those with solitary diagnoses of either TBI or facial trauma.

Feline infectious peritonitis (FIP), caused by the feline coronavirus (FCoV), is a devastating dis-ease in cats. Based on its antigenicity, FCoV can be divided into two serotypes: FCoV-I and FCoV-II. Furthermore, according to its pathogenicity, FCoV can be divided into feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). There are numerous factors that affect the pathogenesis of FIP, among which host immunity and viral genetics can play an es-sential role in the development of FIP. Owing to the lack of specific symptoms, existing individual diagnostic methods can only support the suspicion of FIP, and multiple diagnostic methods and test data need to be combined to make a diagnosis. Although there are still no effective FIPV vaccines or commercial drugs available in the market, various studies have shown that some compounds can be used for treatment. Therefore, FIP is no longer incurable in cats

Rapid, accurate, and convenient diagnosis is essential for effective disease management. Various detection methods, such as enzyme-linked immunosorbent assay, have been extensively used, with lateral flow immunoassay (LFIA) recently emerging as a major diagnostic tool. Nanoparticles (NPs) with characteristic optical properties are used as probes for LFIA, and researchers have presented various types of optical NPs with modified optical properties. Herein, we review literature on LFIA with optical NPs for the detection of specific targets in the context of diagnostics.

Background: Endoscopic Ultrasound (EUS) is widely used for the diagnosis of bilio-pancreatic and gastrointestinal (GI) tract diseases, for the evaluation of subepithelial lesions, and for sampling of lymph nodes and solid masses lo-cated next to the GI tract. The role of Artificial Intelligence in healthcare in growing. This review aimed to provide an overview of the current state of AI in EUS from imaging to pathological diagnosis and training. Methods: AI algorithms can assist in lesion detection and characterization in EUS by analysing EUS images and identifying suspicious areas that may require further clinical evaluation or biopsy sampling. Deep learning tech-niques, such as convolutional neural networks (CNNs), have shown great potential for tumour identification and subepithelial lesion (SEL) evaluation by extracting important features from EUS images and using them to classify or segment the images. Results: AI models with new features can increase the accuracy of diagnoses, provide faster diagnoses, identify subtle differences in disease presentation that may be missed by human eyes, and provide more information and in-sights into disease pathology. Conclusions: The integration of AI in EUS images and biopsies has the potential to improve the diagnostic accura-cy, leading to better patient outcomes and to a reduction of repeated procedures in case of non-diagnostic biopsies.

Background: Due to the importance of brain death (BD) diagnostic do not mistake, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. Methods: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative data from the ICP waveforms were extracted and analyzed comparing BD patients and health subjects. Results: Fifteen patients were included. ICP waveforms presented substantial differences amidst BD patients when compared to the control group. Moreover, pulse amplitude and time to peak variables values in the case group were also statistically significant. Conclusions: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.

We hypothesized that biofilm production occurs on stainless steel when incubated with tissue specimens in thioglycolate broth media (TBM). In a diabetic foot infection (DFI) cohort, applying the Kirschner wire and conventional methods were more sensitive than applying only the latter (CI 90%; 0.167 versus 0.375).

Background and Objectives: The IPED study showed that a smartphone-based event recorder increased the number of patients in whom an ECG was captured during symptoms over five-fold to more than 55% at 90 days compared to standard care [1] and concluded that this safe, non-invasive and easy to use device should be considered part of on-going care to all patients presenting acutely with unexplained palpitations or pre-syncope. This study reports the process of establishing a smartphone palpitation and pre-syncope service. Materials and Methods: A clinical Standard Operating Procedure (SOP) was devised, and funding was secured through a business case for the purchase of 40 AliveCor devices in the first instance. The clinic was launched on 22nd July 2019. Results: Between 22nd July 2019 and 31st October 2019, 68 patients seen in the ED with palpitations or pre-syncope were referred to SPACC. 30 were male and 38 female and mean age was 45.8 (SD 15.1) with a range from 18 to 80 years. 50 (74%) patients underwent full investigation. 7 (11%) patients were deemed on first assessment to have non-cardiac palpitations and were not fitted with the device. All patients who underwent full investigation achieved symptomatic rhythm correlation most with sinus rhythm, ventricular ectopics or bigeminy. A symptomatic cardiac dysrhythmia was detected in 6 (8.8%) patients. 3 patients had supraventricular tachycardia; SVT (4%), 2 had atrial fibrillation (3%) and 1 atrial flutter (2%). Qualitative feedback from the SPACC team suggested several areas where improvement to the clinic could be made. Conclusion: We believe a smartphone palpitation service based in ambulatory care is simple to implement and is effective at detecting cardiac dysrhythmia in ED palpitation patients.

Li-ion battery packs are the heart of modern electric vehicles. Due to their perishable nature, it is crucial to supervise them closely. In addition to on-board supervision over safety and range, insights into the battery’s degradation are also becoming increasingly important, not only for the vehicle manufacturers but also for vehicle users. The concept of digital twins has already emerged on the field of automotive technology, and can also help to digitalize the vehicle’s battery. In this work, we set up a data pipeline and digital battery twin to track the battery state, including state of charge (SOC), state of health (Capacity) (SOHc ) and state of health (Resistance) (SOHr ). To achieve this goal, we reverse-engineer the diagnostics interface of a 2014 e-Golf to query for Unified Diagnostic Services (UDS) messages containing both battery pack and cell-individual data. An on-board diagnosis (OBD) logger records the data with edge-processing capability. Pushing this data into the cloud twin system using IoT-technology, we can fit battery models to the data and infer cell individual internal resistance from them. We find that the resistances of the cells differ by a magnitude of two. Furthermore, we propose an architecture for the battery twin in which the twin fleet shares resources like models by encapsulating them in Docker containers run on a cloud stack. By using web technology, we present the analyzed results on a web interface.

Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second cause of cancer death by 2022. For nearly 80% of patients, diagnosis occurs at an advanced, non-surgical stage, making such patients incurable. Gemcitabine is still an important component in PDAC treatment and is most often used as a backbone to test new targeted therapies and there is, to date, no routine biomarker to predict its efficacy. Samples from a phase III randomized trial were used to develop trough a large approach based on blood-based liquid biopsy, transcriptome profiling, and machine learning, a 9 gene predictive signature for gemcitabine sensitivity. Patients with a positive test (41.6%) had a significantly longer progression free survival (PFS) (3.8 months vs. 1.9 months p=0.03) and a longer overall survival (OS) (14.5 months vs. 5.1 p<0.0001). In multivariate analyses, this signature was independently associated with PFS (HR=0.5 (0.28-0.9) p=0.025) and OS (HR=0.39 (0.21-0.7) p=0.002).

This study was to investigate and assess salivary biomarkers as a means of diagnosing periodontitis. A total of 121 subjects were included: 28 periodontally healthy subjects, 24 with stage I, 24 with stage II, 23 with stage III, and 22 with stage IV periodontitis. Salivary proteins including active matrix metalloproteinase-8 (MMP-8), pro-MMP-8, total MMP-8, C-reactive protein, secretory immunoglobulin A and planktonic bacteria including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas nigrescens, Parvimonas micra, Campylobacter rectus, Eubacterium nodatum, Eikenella corrodens, Streptococcus mitis, Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, and Actinomyces viscosus were measured from salivary samples. The performance of the diagnostic models was assessed by receiver operating characteristics (ROC) and area under the ROC curve (AUC) analysis. The diagnostic models were constructed based on the subjects’ proteins and/or microbial profiles, resulting in two potential diagnosis models, which achieved better diagnostic powers with an AUC value &gt; 0.750 for the diagnosis of stage II, III, and IV periodontitis (Model PC-I; AUC: 0.796, sensitivity: 0.754, specificity: 0.712) and for the diagnosis of stage III and IV periodontitis (Model PC-II; AUC: 0.796, sensitivity: 0.756, specificity: 0.868). This study can contribute to screening for periodontitis based on salivary biomarkers.

The detection of coronavirus (COVID-19) is now a critical task for the medical practitioner. The coronavirus spread so quickly between people and approaches 100,000 people worldwide. In this consequence, it is very much essential to identify the infected people so that prevention of spread can be taken. In this paper, the deep feature plus support vector machine (SVM) based methodology is suggested for detection of coronavirus infected patient using X-ray images. For classification, SVM is used instead of deep learning based classifier, as the later one need a large dataset for training and validation. The deep features from the fully connected layer of CNN model are extracted and fed to SVM for classification purpose. The SVM classifies the corona affected X-ray images from others. The methodology consists of three categories of Xray images, i.e., COVID-19, pneumonia and normal. The method is beneficial for the medical practitioner to classify among the COVID-19 patient, pneumonia patient and healthy people. SVM is evaluated for detection of COVID-19 using the deep features of different 13 number of CNN models. The SVM produced the best results using the deep feature of ResNet50. The classification model, i.e. ResNet50 plus SVM achieved accuracy, sensitivity, FPR and F1 score of 95.33%,95.33%,2.33% and 95.34% respectively for detection of COVID-19 (ignoring SARS, MERS and ARDS). Again, the highest accuracy achieved by ResNet50 plus SVM is 98.66%. The result is based on the Xray images available in the repository of GitHub and Kaggle. As the data set is in hundreds, the classification based on SVM is more robust compared to the transfer learning approach. Also, a comparison analysis of other traditional classification method is carried out. The traditional methods are local binary patterns (LBP) plus SVM, histogram of oriented gradients (HOG) plus SVM and Gray Level Co-occurrence Matrix (GLCM) plus SVM. In traditional image classification method, LBP plus SVM achieved 93.4% of accuracy.

To date, viral RNA detection is almost the only way to confirm SARS-CoV-2infectionin practice.However, variousreasons can cause low sensitivity for RNA detection, and thisposes aserious challenge to disease control. We tested the performance of detecting total antibody(Ab) and IgM levels in serum by the methods of chemiluminescence, enzyme-linked immunosorbent assay (ELISA), and colloidal golddetection. The datashowed that the sensitivity and specificity for detecting total Ab and IgM levels were high by all three methods, and the sensitivity was higher for detecting total Ab than for detecting IgM. Evidence from studieshas shown thatviral RNA testingcombinedwith serological testing could increase the diagnostic sensitivity while maintaining a high specificity. Specific serology testsfor SARS-CoV-2 havegreat value for clinical practice and public health.

Molecular imaging modalities are used for different type of cancers detection and diagnosis. In recent few years, there has been an increased focus on developing novel nanoparticles as new imaging contrast agents for early detection of cancer. The aim of this review article is to summarize molecular imaging technologies accompanying with using nanoparticles to improve potential imaging for cancer detection and hence valuable therapy in the future. Nanoprobes are rapidly becoming potentially transformative tools on cancer diagnostics for a wide range of imaging modalities such as CT, MRI, SPECT, PET, Ultrasound and Optical imaging. The study results seen in the recent literature are provided and discussed the diagnostic performance of imaging modalities for cancer diagnosis and their future directions. With knowledge of the correlation between the application of nanoparticles and molecular imaging modalities and with the development of targeted contrast agents or nanoprobes, they may provide better cancer diagnosis in the future.

Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system on immune checkpoint inhibitor efficacy and toxicity. We provide an overview of the impact of cellular senescence in normal and pathological contexts and examine recent studies that have connected aging and cellular senescence to immune checkpoint inhibitor treatment in both the pre-clinical and clinical contexts. Overall, senescence plays a multi-faceted, context-specific role, and has been shown to modulate immune-related adverse event incidence as well as immune checkpoint inhibitor response.

Climate change related increases in frequency and intensity of heatwaves affect viticulture, leading to losses in yield and grape quality. We assessed whether canopy architecture manipulation mitigates the effects of summer stress in a Mediterranean vineyard. Muscat of Alexandria grapevines were monitored during 2019-2020. Two canopy shoot positioning treatments were applied: Vertical shoot positioning (VSP); and Modulated shoot positioning (MSP), the west side upper foliage released to promote partial shoot leaning, shading the clusters. Clusters were sampled at pea size (PS), veraison (VER) and full maturation (FM). Measurements included rachis anatomy and hydraulic conductance, and aquaporins (AQP) and stress-related genes expression in cluster tissues. Results show significant seasonal and interannual differences in Kh and vascular anatomy. At VER, Krachis , Krachis+pedicels, and xylem diameter decreased but were unaffected by treatments. The Phloem/Xylem ratio was either increased (2019) or reduced (2020) in MSP, compared to VSP. Most AQP were down-regulated at FM in pedicels, and up-regulated at VER in pulp. A potential maturation shift in MSP was observed, confirmed by the up-regulation of several stress-related genes in all tissues. The study pinpoints the role of canopy architecture in berry water relations and stress response during ripening.

Purpose: The purpose of this study is to apply the Composite Radiographic Index modified (CRIm) in CBCT scans of patients with Medication related osteonecrosis of the jaws (MRONJ) in order to detect its validity, and corelate the radiologic findings with the clinical staging of the disease. Methods: This study included 43 patients with MRONJ diagnosis and CBCT scans performed in the School of Dentistry and approved by the Research Ethics Committee. Clinical staging for every patient (0-3) was provided according to AAOMS 2022 guidelines. In cases of patients with both jaws affected, each jaw was evaluated independently resulting to 52 CBCT scans. The 52 CBCT scans were assessed under standardized viewing conditions by 2 observers who evaluated independently the following 8 radiologic features: lytic changes, sclerosis, periosteal reaction, sequestration, non-healing extraction sockets and other findings (sinus implication, inferior alveolar canal involvement, jaw fracture). The CRIm index was constructed to assess the extent of osseous changes. The radiologic features were scored as absent (0), localized/single (1), extensive/multiple (2), yielding a theoretical range of 0–12. For statistical analysis Fisher’s exact test and Spearman’s correlation coefficient were performed. Results: A statistically significant association of clinical stage with lytic changes, sequestration and inferior alveolar canal involvement was found. Also, a statistically significant correlation of clinical stage with CRIm index classification was obtained. Conclusions: The CRIm index tends to increase as the clinical stages of MRONJ advance, suggesting a correlation between the clinical stage of MRONJ and the CRIm index.

Although migraine belongs to the main causes of disability worldwide the mechanisms of its pathogenesis are poorly known, which is among the reasons that this disease is underdiagnosed and undertreated. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective markers of its occurrence and severity. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. Migraine patients displayed lower urinary levels of 5-HIAA and KYNA, but KYN and QA were enhanced as compared with the controls. Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios. Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score, monthly migraine, and monthly headache days. A negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be an easy-to-determine marker of migraine occurrence and severity and may contribute to the identification of migraine patients with depression.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

Abstract: Exercise has been repeatedly shown to be safe and beneficial for cancer survivors. However, there is no normative guideline for exercise prescription, and it is under exploration. Therefore, this literature review aims to provide some advice for the formulation of exercise prescriptions for patients with breast cancer-related lymphedema (BCRL) from the perspective of reducing lymphedema severity. A review of relevant studies published before November 2023 was conducted using three scientific databases PubMed, Embase, and Scopus. A total of 2696 articles were found. Eventually, 13 studies fulfilled the inclusion criteria and were included in this literature review. We concluded daily, or nearly daily exercise at home can be recommended. Moreover, reduced lymphedema severity may not be maintained after ceasing the exercise program, so exercise should be a lifelong practice.

To investigate the associated mechanisms concerning collagen and the expression of apoptosis-related proteins in porcine skin injuries induced by laser exposure, pig skin was treated with a 1064 nm laser. The healing process of the laser-treated areas, alterations in collagen structure, and changes in apoptosis were continuously observed and analyzed from 6 hours to 28 days post-irradiation. On the 28th day following exposure, wound contraction and recovery were notably sluggish in the medium-high dose groups, displaying more premature and delicate type III collagen within the newly regenerated tissues. The collagen density in these groups was roughly 37-58% of that in the normal group. Between days 14 and 28 after irradiation, there was a substantial rise in apoptotic cell count in the forming epidermis and granulation tissue of the medium-high dose group, in contrast to the normal group. Notably, the expression of proapoptotic proteins bax, caspase-3, and caspase-9 surged significantly 14 days after irradiation in the medium-high dose groups and persisted at elevated levels on the 28th day. During the later stage of wound healing, the augmented apoptotic cell population and insufficient collagen generation in the newborn skin tissue of the medium-high dose groups were closely associated with delayed wound recovery.

Breast cancer-related lymphedema (BCRL) affects approximately 20% of women after breast cancer therapy. Advances in treatment have increased life expectancy, thus the prevalence of BCRL will continue to rise with the number of cancer survivors. Hence the need to develop strategies to prevent this condition. We provide a systematic review of the literature on primary prevention of BCRL by prophylactic lymphatic surgery (PLS). Between June and August 2022, we conducted a search of PubMed, Google Scholar and Cochrane. In the end a total of eighteen papers were selected. The eleven studies without a control group reported only 15 of 342 patients who developed lymphedema at least six months after PLS (4.59%). The seven studies with a control group included 569 patients, 328 cases and 241 controls. Among the cases, 36 (10%) developed lymphedema. In contrast, the incidence of lymphedema in controls was 40% (98 of 241 patients). Formulation of definite recommendations in favour of PLS is hindered by low-quality studies. There is no consensus on which technique should be preferred, nor on whether adjuvant radiotherapy might affect the efficacy of PLS. Randomized controlled trials are mandatory to conceive evidence-based recommendations.

Online transportation services, initially presented as an innovative employment approach by categorizing workers as 'independent contractors', have come to be recognized for their exploitative nature. The notion of 'flexibility' suggests that workers have the autonomy to tailor their hours and location according to their income goals. However, this disguises the true situation for informal workers who lack rights and protections. This study delves into these issues from a psychological standpoint to uncover the mental and emotional interplay between the motivations and exploitation experienced by online drivers affiliated with multiple platforms. The study adopts a qualitative methodology with a phenomenological lens. Data was gathered through thorough interviews, observations, and document analysis, with Interpretative Phenomenological Analysis (IPA) employed as the data analysis technique. The study's participants were five male multi-platform online drivers from the Special Region of Yogyakarta, ranging in age from 18 to 64, and had been associated with at least two platforms for more than a year. The findings highlight two primary themes: firstly, the decision to join multiple platforms is chiefly driven by economic reasons, including a decline in orders, daily earnings, bonus incomes, and the conclusion of the initial profitable phase. Secondly, the exploitative conditions are linked to the platforms' algorithms, which exert control and influence the psychological state of the drivers. Nonetheless, the participants have developed effective strategies to manage fatigue, anxiety, and stress.

The Vitamin D Receptor (VDR) mediates the actions of vitamin D, which has important roles in bone homeostasis, growth/differentiation of cells, immune functions and reduction of inflammation. Emerging evidences suggest that epigenetic modifications of the VDR gene, particularly DNA methylation, may contribute to the onset and progression of many human disorders. This review aims to summarize the available information on the role of VDR methylation signatures in different pathological contexts, including autoimmune diseases, infectious diseases, cancer and others. The reversible nature of DNA methylation could enable the development of therapeutic strategies, offering new avenues for the management of these worldwide diseases.

Vulvovaginal candidiasis (VVC) is a prevalent condition affecting women worldwide. This study aimed to develop a rapid qPCR assay for accurate identification of VVC etiological agents and reduced azole susceptibility. One hundred and twenty nine vaginal samples from an outpatient clinic (Bilbao-Spain) were analyzed using culture-based methods and multiplex qPCR targeting fungal species, Candida albicans being the predominant species. Antifungal susceptibility tests revealed reduced azole susceptibility in three (3,48%) isolates. Molecular analysis identified several mutations in genes associated with azole resistance and novel mutations in TAC1 and MRR1 genes were also identified, which could contribute to drug resistance.

Introduction: congenital ureteral stenosis is one of the leading causes of impaired urinary drainage and subsequent dilatation of urinary collecting system, known as hydronephrosis or ureterohy-dronephrosis. Mechanism that leads to obstruction is not clearly known. Multiple studies in rat models have shown increased angiotensin 11 and TGFβ levels in obstructed ureteral tissue. The aim of the study is to investigate expression of fibrosis related genes in obstructive and normal ureteral tissue. Material and methods: it is a monocentric study in which nineteen patients were selected prospec-tively. 17 patients of which underwent Hynes-Anderson pyeloplasty due to the PUJO, 2 patients underwent ureteroneocystostomy due to ureterovesical junction obstruction (UVJO) and 6 patients were chosen for control group: 5 underwent nephrectomies due to the kidney tumor and 1- upper pole heminephrectomy due to the duplex kidney with normal pyeloureteric junctions in all. Tissue RNA was chemically extracted after freezing the biopsy samples in liquid nitrogen, with cDNA synthesis performed immediately after nucleic acid isolation. qPCR to evaluate the relative expres-sion of Tgfb1, Mmp1, Timp1, Pai1, Ctgf and Vegfa was performed. Expression levels of Gapdh and Gpi genes (geometric average) were used to calculate the relative expression of the investigated genes. Outliers were removed prior to calculating confidence intervals for the experimental groups, and Wilcoxon rank-sum test was performed to determine statistical significance of the differences. Results: significant differences between healthy and stenotic tissue samples in Ctgf gene expression levels were observed, with the samples from afflicted tissue showing lower expression. No statistical difference in expression levels of Tgfb1, Timp1, Vegfa, Mmp1, Pai1 was found. Discussion and conclusions: These findings suggest that tissue fibrosis similar to other tissues and organs is not the leading cause of stenosis, at least at the moment of surgery. Decreased CTGF ex-pression is indicative of developmental origin of obstruction.

The vacuolar H+-ATPase is a multisubunit enzyme which plays an essential role in the acidification and functions of lysosomes, endosomes, and synaptic vesicles. Many genes encoding subunits of V-ATPases, namely ATP6V0C, ATP6V1A, ATP6V0A1 and ATP6V1B2, have been associated with neurodevelopmental disorders and epilepsy. The autosomal dominant ATP6V1B2 p.Arg506* variant can cause both deafness, congenital, with onychodystrophy, autosomal dominant (DDOD) and deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndromes (DOORS). Some but not all individuals with this truncating variant have intellectual disability and/or epilepsy, suggesting incomplete penetrance and/or variable expressivity. To further explore the impact of the p.Arg506* variant in neurodevelopment and epilepsy, we generated Atp6v1b2emR506* mutant mice and performed standardized phenotyping using the International Mouse Phenotyping Consortium (IMPC) pipeline. In addition, we assessed the EEG profile and seizure susceptibility of Atp6v1b2emR506* mice. Behavioral tests revealed that the mice present locomotor hyperactivity and show less anxiety-associated behaviors. Moreover, EEG analyses indicate that Atp6v1b2emR506* mutant mice have interictal epileptic activity and that both heterozygous (like patients) and homozygous mice have reduced seizure thresholds to pentylenetetrazol. Our results confirm that variants in ATP6V1B2 can cause seizures and that the Atp6v1b2emR506* heterozygous mouse model is a valuable tool to further explore the pathophysiology and potential treatments for vacuolar ATPases-associated epilepsy and disorders.

In this study, we de novo assembled whole genomes of two small body-sized West Pacific sciaenids (Larimichthys polyactis and Collichthys lucidus) and compared them with published genome data of two closely-related, large body-sized species (Larimichthys crocea and Miichthys miiuy) and one distantly-related, large body-sized outgroup species (Dicentrarchus labrax). The phylogeny constructed using 7,403 single-copy orthologs shared among the five species indicated that L. crocea and L. polyactis diverged about 42 MYA. The two sibling taxa are more closely-related to C. lucidus than M. miiuy. We further identified four growth-related genes (CDHR2, PGC, PTN and PDGFA) that host five diagnostic amino acid variants on body size traits in the fishes, splitting small-body sized L. polyactis and C. lucidus from large-body sized L. crocea, M. miiuy and D. labrax. The results provide new genomic resources and guidelines to facilitate future endeavors in studying functional genomics and developing selective breeding programs for desirable growth traits in sciaenids.

Exposure to extreme heat is a known risk factor that is associated with increased heat-related illness (HRI) outcomes. The relevance of heat wave definitions could change across the health conditions and geographies due to the heterogenous climate profile. This study compared the sensitivity of 28 heat wave definitions associated with HRI emergency department visits over five summer seasons (2011-2016), stratified by two physiographic regions (Coastal and Piedmont) in North Carolina. The HRI rate ratios associated with heat waves were estimated using the generalized linear regression framework assuming a negative binomial distribution. We compared the Akaike Information Criterion (AIC) values across the heat wave definitions to identify an optimal heat wave definition. In the Coastal region, heat wave definition based on daily maximum temperature with a threshold >90^th percentile for two or more consecutive days had the optimal model fit. In the Piedmont region, heat wave definition based on the daily minimum temperature with a threshold value >90^th percentile for two or more consecutive days was optimal. Additionally, we observed that the optimal heat wave definitions from this study captured moderate and frequent heat episodes than the national weather service (NWS) heat products that worked best for extreme heat episodes. This study compared the HRI morbidity risk associated with epidemiologic-based heat wave definitions and with NWS heat products. Our findings could be used for public health education and suggest recalibrating NWS heat products.

Abstract: Windtech device is a novel tool for measuring the sensation of the ‘cold’. Cold poses numerous challenges for industrial operations, human survival, and living convenience. The impact of the cold is not possible to be quantified just based on temperatures; however other factors such as wind speed, humidity, irradiance have to be taken into consideration. Efforts have been made to develop combined indices such as wind chill temperature (WCT), AccuWeather RealFeel®, and others. The presented article discusses these along with the industrial standards that emphasize on the quantification of the ‘cold’. The following article introduces the Windtech device and its operating principle involving ‘heated temperature’, where the ‘heated temperature’ is affected by environmental parameters including ambient temperature, humidity, wind velocity, and irradiance. The discussed Windtech device is calibrated for operation according to the ISO 11079:2007 standard.

The aim of this study was to evaluate the relationship between serum levels of advanced glycation end products (AGEs) and abdominal aortic calcification (AAC) in patients with type 2 diabetes mellitus (DM2). This was a prospective cross-sectional study conducted from January 2017 to June 2018. One-hundred and four consecutive patients with DM2 were given lateral lumbar X-rays in order to quantify aortic abdominal calcification AAC. Circulating levels of AGEs and classical cardiovascular risk factors were determined. Clinical history was also registered. Patients with higher AGEs values had higher grades of aortic calcification and higher number of diabetic related complications. Multivariate logistic regression analysis showed that being older, male and having high levels of AGEs and triglycerides were the independent risk factors associated to moderate-severe AAC when compared to no-mild AAC. Our results suggest that AGEs plays a role in the pathogenesis of aortic calcifications. In addition, the measurement of AGEs levels may be useful for assessing the severity of AAC in the setting of diabetic complications.

Objective: To examine the associations between menstruation features and symptoms and hormone-immune-metabolic biomarkers. Methods: Forty-one women completed questionnaires assessing characteristic menstruation symptoms, duration of menstrual cycle and number of pads used/day and completed the Daily Record of Severity of Problems (DRSP) during the consecutive days of their menstrual cycle. Menses-related symptoms (MsRS) were computed from the sum of 10 pre- and post-menses symptoms and the menstruation blood and duration index (MBDI) was computed based on the daily number of pads and duration of menses. We assayed serum levels of various biomarkers at days 7, 14, 21, and 28 of the subjects’ menstrual cycle. Results: MBDI was significantly associated with a) MsRS including low abdominal cramps, and gastro-intestinal (GI) and pain symptoms (positively); b) plasma levels of haptoglobin (Hp), CCL5, insulin growth factor (IGF)-1, and plasminogen activator inhibitor (PAI)1 (all positively); and c) estradiol and paraoxonase (PON)1 arylesterase activity (both inversely). MsRS were significantly predicted by CCL5 and IGF-1 (both positively) and progesterone (inversely). Low-abdominal cramps, and gastro-intestinal and pain symptoms were associated with lower progesterone levels. The MBDI+MsRS score was significantly predicted by the cumulative effects of (in descending order of importance): Hp, IGF-1, PON1 arylesterase, estradiol and PAI. Conclusion: Menstruation-related features including estimated blood loss, duration of menses, cramps, pain and GI symptoms are associated with hormone-immune-metabolic biomarkers, which mechanistically may explain those features. Women with an increased MBDI+MsRS index ≥ 0.666 percentile may be considered to have menstruation-related distress, including dysmenorrhea symptoms.

Disease related malnutrition (DRM) is prevalent in hospitals and is associated with increased care needs, prolonged hospital stay, delayed rehabilitation and death. Nutrition care process related activities such as screening, assessment and treatment has been advocated by scientific societies and patient organizations but implementation is variable. We analyzed the cross-sectional nutritionDay database for prevalence of nutrition risk factors, care processes and outcome for medical patients. In 59126 medical patients included between 2006-2015 the prevalence of recent weight loss (45%), history of decreased eating (48%) and low actual eating (53%) was more prevalent than low BMI (8%). Each of these risk factors was associated with a large increase in 30 days hospital mortality. Nutrition care processes increases slightly with presence of risk factors but never done in more than 50% of patients. Only a third of patients not eating in hospital receive oral nutritional supplements or artificial nutrition. We suggest that political action should be taken to raise awareness and formal education on all aspects related to DRM for all stakeholders, to create and support responsibilities within hospitals, and to create adequate reimbursement schemes. Collection of routine and benchmarking data is crucial to tackle DRM.

Background: Antibiotic lock therapy is an interventional modality used for treatment and prevention of central-line associated bloodstream infections. Stability and compatibility data for combinations are lacking, limiting clinical use. Objective: Compatibility and stability of daptomycin lock solutions in combination with azithromycin, gentamicin, and heparin or sodium citrate were evaluated up to 96 hours. Methods: Eight candidate lock solutions were prepared for compatibility and stability testing. All solutions were prepared in glass vials, and included daptomycin 1mg/mL in varying combinations with heparin 100 – 1,000 units/mL, trisodium citrate, azithromycin and/or gentamicin. Lactated Ringer’s solution was added as a diluent in a sufficient quantity to bring the total volume up to 5mL. Drug stability in the admixture was determined by the degradation of the components. The quantification of drugs was performed using Waters Alliance HPLC using Phenomenex Luna C8 (2), 150*2.6mm, 5µ column. A gradient run was executed for 20 minutes with 0.45% ammonium dihydrogen phosphate, pH 3.25 as eluent A and acetonitrile as eluent B at a flow rate of 1.0mL/min. Each solution was visually inspected for particulates and color change. Lock solutions were tested in triplicate. Results: Daptomycin degradation was <10% for all solutions at 48 hours, and for 7 of the 8 solutions at 72 hours. Gentamicin degradation was <5% for solutions in combination with daptomycin and trisodium citrate. No physical incompatibilities were detected. Conclusion: Study data support the stability and compatibility of daptomycin with additives in solution, allowing for fewer exchanges and longer dwell times for a lock solution. The addition of azithromycin or gentamicin may offer synergy and/or extended spectrum of activity. Daptomycin bioactivity with trisodium citrate needs confirmation.

The link between language processing and motor systems has been the focus of increasing interest to Cognitive Neuroscience. Some classical papers studying Event Related Potentials (ERPs) induced by linguistic stimuli have found differences in electrophysiological activity when comparing action and non-action words; more specifically, a bigger p200 for action words. On the other hand, a series of studies have validated the use of a grip force sensor (GFS) to measure language-induced motor activity during both isolated words and sentence listening, finding that action words induce an augmentation in the grip force around 250-300 ms after the onset of the stimulus. The purpose of the present study is to combine both techniques to assess if the p200 is related to the augmentation of the grip force measured by a GFS. We measured ERP and GFS changes elicited by listening to action and non-action words while maintaining an active grasping task in 10 healthy subjects. Our results show that the amplitude of the p200 in central electrodes is correlated to the augmentation in the GFS around 300 ms induced by linguistic stimuli. To our knowledge, this is the first study where the electrophysiological activity and the changes in the grip force induced by auditory language processing are put together, opening new venues of interpretation for the sensorimotor interaction in language processing.

The mechanization of agricultural activities has led to indiscriminate deposition of toxic xenobiotics, including organophosphates in the biomes, and this has led to intoxication characterized with deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP) on neuro-cognitive performance and anxiety-like behaviors in rats Thirty-two adult male Wistar rats (150 – 170g) were randomly divided into 4 groups, orally exposed to normal saline (NS), DDVP (8.8mg/kg), CPF (14.9mg/kg) and DDVP+CPF for 14 consecutive days. On day 10 of exposures, anxiety-like behaviors and amygdala dependent fear learning were assessed using Open Field and Elevated Plus Maze paradigms respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following 3 training trials each on days 11, 12 and 13. On day 15, the rats were euthanized, and their brains excised, hippocampus and amygdala removed, 5 of which were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three processed for histology (cresyl violet stain) and proliferative marker (Ki67 immunohistochemistry). Marked (p≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damages are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.

Background: Differentiating essential tremor (ET) and functional tremor (FT) remains challenging due to their overlapping clinical presentations. Objective: In this study, we aimed to elucidate the demographic and psychometric differences between the aforementioned tremor types to enhance the diagnostic accuracy and therapeutic strategies. Methods: In this prospective study, we included 96 patients diagnosed with ET or FT and analysed their related demographic data, clinical symptoms, and psychometric evaluation scores. Our statistical analysis involved Pearson’s chi-square tests, Fisher’s exact tests, and logistic regression to assess how the different variables impact tremor diagnosis. Results: Our study demonstrated a higher ET prevalence in males (p = 0.015). Furthermore, we demonstrated that patients with ET displayed a significantly lower body mass index and a lower age of onset compared to those with FT (p = 0.050 and p = 0.023, respectively). Our psychometric assessments revealed higher cognitive and body image scores in patients with ET, whereas those with FT scored higher on depression and anxiety scales. The misdiagnosis rate was 14.5%, emphasising the need for improved diagnostic criteria. Conclusions: We established specific demographic and psychometric distinctions between ET and FT, which could potentially benefit clinicians in making accurate diagnoses and tailoring treatment approaches. These findings support the inclusion of comprehensive psychometric evaluations into standard diagnostic procedures to better differentiate tremor types.

BackgroundIntracranial hemorrhage (ICH) in pregnancy, estimated at 1 in 10,000 cases, presents significant diagnostic challenges prenatally despite advanced imaging techniques such as ultrasound (US) and MRI. Detecting ICH is crucial for pregnancy management and future treatment decisions aimed at improving fetal survival and reducing brain damage. This report presents the diagnosis and outcomes of two cases of prenatal ICH.Cases presentationThe first case involves a 30-year-old pregnant woman with irregular prenatal care diagnosed with ICH at 32 weeks of gestation via US and MRI. She chose to continue the pregnancy, delivering a 3160g male infant at 36 weeks via cesarean section. Following NICU care including resuscitation and ventriculoperitoneal shunt placement, the infant was discharged. Subsequent examinations showed a reduction in ventricle size. In the second case, a 27-year-old woman taking acenocoumarol for a mechanical heart valve developed fetal subdural hemorrhage detected by US and MRI. She opted to terminate the pregnancy, resulting in a stillborn male infant weighing 1530g.ConclusionFetal ICH presents with varying severity and prognostic implications, diagnosed and graded using US. Fetal cranial MRI may help clarify the etiology. Management remains controversial, with termination of pregnancy potentially warranted in severe cases due to poor prognosis. Further research is needed to refine management and improve outcomes in fetal ICH.

Spinal cord tumors, though rare, present formidable challenges in clinical management due to their intricate nature. Traditional treatment modalities like surgery, radiation therapy, and chemotherapy have been the mainstay for managing these tumors. However, despite significant advancements, challenges persist, including the limitations of surgical resection and the potential side effects associated with radiation therapy. In response to these limitations, a wave of innovative approaches is reshaping the treatment landscape for spinal cord tumors. Advancements in gene therapy, immunotherapy, and targeted therapy are offering groundbreaking possibilities. Gene therapy holds the potential to modify the genes responsible for tumor growth, while immunotherapy harnesses the body's own immune system to fight cancer cells. Targeted therapy aims to strike a specific vulnerability within the tumor cells, offering a more precise and potentially less toxic approach. Additionally, novel surgical adjuncts are being explored to improve visualization and minimize damage to surrounding healthy tissue during tumor removal. These developments pave the way for a future of personalized medicine for spinal cord tumors. By delving deeper into the molecular makeup of individual tumors, doctors can tailor treatment strategies to target specific mutations and vulnerabilities. This personalized approach offers the potential for more effective interventions with fewer side effects, ultimately leading to improved patient outcomes and a better quality of life. This evolving landscape of spinal cord tumor management signifies the crucial integration of established and innovative strategies to create a brighter future for patients battling this complex condition.

Abstract Objective: This study aims to examine CA-125 and miRNAs as biomarkers in endometriosis pathophysiology and their potential roles in clinical diagnostics and prognostics. Methods:We reviewed a variety of studies, including cross-sectional, case-control, and prospective designs, examining a broad spectrum of patient demographics, clinical features, and biomarker (CA-125 and miRNA) expression levels. Results: CA-125 has been reaffirmed as a valuable biomarker in diagnosing and monitoring endometriosis, with its utility enhanced when used alongside other markers. MiRNAs have emerged as promising molecular regulators, offering new avenues for non-invasive diagnostics and a deeper understanding of the disease's pathophysiology. The integration of these biomarkers presents a potential shift towards more personalized and effective diagnostic and therapeutic strategies. Conclusion: Endometriosis presents a significant challenge in women's health, requiring innovative approaches for its management. The convergence of CA-125 and miRNA research represents a promising advance, potentially leading to more accurate diagnostics and personalized treatment. Future research should focus on standardizing methodologies, expanding study cohorts, and integrating findings into clinical practice to fully harness the potential of these biomarkers.

Abstract: Canine ehrlichiosis is a zoonotic disease transmitted by ticks, posing a formidable challenge to both veterinary and public health sectors worldwide. Across continents and regions, the prevalence rates of Ehrlichia canis exhibit significant variation, underlining the necessity for a nuanced and globally informed approach to understanding and combating this disease. The review navigates through this complexity, shedding light on the intricate pathogenesis of the illness. Central to this understanding is the bacterium's adept manipulation of the host's immune response, contributing to the diverse clinical manifestations observed in infected animals. Diagnostic methodologies, crucial for timely intervention and management, are subjected to critical assessment. From traditional microscopy to modern molecular techniques and serology, each approach is scrutinized for its strengths and limitations. By acknowledging these nuances, the review aims to equip practitioners with the knowledge necessary to make informed diagnostic decisions. A central tenet of this review is the advocacy for an integrated "One Health" approach. By leveraging advancements in genomics, proteomics, and artificial intelligence, there is a potential to enhance diagnostic accuracy and develop innovative therapeutic and preventive strategies globally. This collaborative approach recognizes the interconnectedness of human, animal, and environmental health, offering a holistic framework for tackling complex zoonotic diseases like canine ehrlichiosis. In conclusion, this review serves as a beacon of knowledge, illuminating the multifaceted landscape of canine ehrlichiosis. Through its synthesis of scientific literature and emphasis on methodological rigor, it provides a foundation upon which future research and interventions can be built. With a unified commitment to "One Health" principles and the integration of cutting-edge technologies, there exists the potential to mitigate the impact of this disease and safeguard both animal and human well-being worldwide

Autoimmune hemolytic anemias (AIHAs) are conditions whereby a person produces an antibody to their own red blood cells (RBCs). These conditions can be primary with unknown cause or secondary, associated with diseases or infections. There are seven different categories of AIHA, warm-antibody AIHA (wAIHA); cold-antibody AIHA that includes cold agglutinin syndrome (CAS) and cold agglutin disease (CAD); mixed AIHA, also called combined cold and warm AIHA; paroxysmal cold hemoglobinuria (PCH) also termed Donath-Lansteiner test-positive AIHA; direct antiglobulin test-negative AIHA (DAT-neg AIHA); drug-induced immune hemolytic anemia (DIIHA); and passenger lymphocyte syndrome. This review will discuss each of these AIHAs and provide information on diagnosis and treatment.

In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th) was published. The importance of understanding the molecular genetics of thyroid tumors as revealed by large-scale genomic analyses such as The Cancer Genome Atlas (TCGA). Consequently, the WHO 5th was fundamentally revised, resulting in a systematic classification based on tumor cell-of-origin and clinical risk. This paper outlines following critical points of the WHO 5th. 1. Genetic mutations in follicular cell-derived neoplasms (FDN) highlight the role of mutations in the MAP kinase pathway, including RET, RAS, and BRAF, as drivers of carcinogenesis. Differentiated thyroid cancers such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) have specific genetic alterations that correlate with morphological classifications: RAS-like tumors (RLTs) and BRAF p.V600E-like tumors (BLTs), respectively. 2. The Framework for benign lesions have revised. The WHO 5th introduces new categories such as "developmental abnormalities" and "thyroid follicular nodular disease" in benign FDN. 3. Low-Risk Tumors include NIFTP, TT-UMP, and HTT. 4. PTC histological variants are reclassified as "subtypes" in the WHO 5th. 5. The concept of high-grade carcinomas is introduced, encompassing poorly differentiated thyroid carcinoma (PDTC), differentiated high-grade thyroid carcinoma (DHGTC), and high-grade medullary thyroid carcinoma (MTC). 6. Squamous cell carcinoma is included in anaplastic thyroid carcinoma (ATC) in the WHO 5th due to shared genetic and prognostic features. 7. Hürthle cell adenoma/carcinoma is renamed oncocytic thyroid adenoma/carcinoma. 8. Other miscellaneous tumors are classified into salivary gland-type carcinomas of the thyroid, thyroid tumours of uncertain histogenesis, thymic tumours within the thyroid, and embryonal thyroid neoplasms. The WHO 5th thus emphasizes the importance of classifying tumors based on genetic abnormalities together with histomorphology, aiding in accurate pathological diagnosis and treatment selection, including molecular-targeted therapies.

Monkeypox virus belongs to the Orthopoxvirus genus, which belongs to the Poxviridae family. The Monkeypox virus is responsible to cause monkeypox, a developing zoonotic disease that has been identified as the most common orthopoxvirus infection in humans in the post-eradication era of smallpox. The virus can be transmitted by a variety of animals, including monkeys and rodents as well as person-to-person. Monkeypox has a clinical presentation that is quite similar to smallpox but mortality is low, in that the febrile prodrome is followed by a period of skin eruption. Monkeypox cases have extended outside the forests of central Africa, where they were first discovered, to other regions of the globe, where they have been imported. This pattern of transmission is most likely related to a global reduction in orthopoxvirus immunity following the discontinuation of smallpox vaccination in 1980, when smallpox was proclaimed eliminated. As a result, monkeypox might become the very common orthopoxvirus infection that affect humans. The emergence of epidemics outside of Africa emphasizes the disease's global significance. Increased monitoring and identification of monkeypox cases are critical tools for gaining a better knowledge of the disease's ever-changing epidemiology.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

Purpose: This study analysed the impact of the COVID-19 pandemic on the diagnosis of malignant neoplasia of the bronchus and lung. Cases diagnosed in the Burgos region in the year prior to the official declaration of the pandemic were compared with those in the year after the pandemic. The research sought to identify whether there was a decrease in the number of cases during the pandemic, and whether this may have led to a delay in diagnosis, reflected in more advanced stages of the disease. Mortality and survival time in each of the periods were also analysed.

Borderline Personality Disorder (BPD) is a complex and severe mental disorder. It is associated with greater use of medical services. It is characterized by intense fear of abandonment, recurring suicidal thoughts or self-harm, paranoid ideation or dissociation, identity difficulties, chronic feelings of emptiness, impulsive behavior and unstable moods and relationships. BPD is one of the most prevalent personality disorders with a higher diagnosis in females. For a diagnosis of BPD in patients, they must have a chronic pattern of functional impairment in addition to five of nine listed DSM-5 criteria. This review was a narrative literature search between 2000 to 2023 with a focus on BPD comorbidities. Results: Researchers observed a complex pattern of comorbidities with BPD that connects with other externalizing and internalizing disorders. BPD has a high comorbidity rate with mood disorders including bipolar I and II disorders, major depressive disorder, anxiety disorders, panic disorder alcohol use disorder, nicotine dependence, marijuana dependance, posttraumatic stress disorder, other personality disorders, binge eating disorder and ADHD. Diagnosis and management of BPD in presence of some of these disorders are discussed.

Photoacoustic imaging (PAI) is a cutting-edge biomedical imaging modality, providing detailed anatomical and functional information about the area beneath the skin surface. Its light energy deposition is such that PAI typically provides clear images of the skin with high signal-to-noise ratios. Specifically, the rich optical contrast of PAI allows biological information related to lesion growth, malignancy, treatment response, and prognosis to be seen. Given its significant advantages and emerging role in imaging skin lesions, we summarize and comment on representative studies of skin PAI, such as the guidance of skin cancer biopsies and surgical excisions, and the accurate diagnosis of psoriasis. We conclude with our insights about the clinical significance of skin PAI, showing how its use to identify biological characteristics in lesion microenvironments allows early diagnosis and prognosis of disease.

Power grid fault diagnosis technology has been widely used at home and abroad. With the access of distributed power sources and diversified loads, the distribution network has changed from a passive network to an active network, and the current has changed from "one-way" to "two-way". The structure of distribution network, equipment environment and operating conditions are becoming more and more complex, and the fault diagnosis and localization of active distribution network is becoming more and more difficult. With the rapid development of artificial intelligence, power grid fault diagnosis based on intelligence is unprecedented. This paper introduces the research status of distributed photovoltaic grid-connected fault diagnosis technology, and expounds the history of fault diagnosis technology, which mainly includes expert system, artificial neural network, Bayesian network, fuzzy set theory, rough set theory, Petri net analytical model and multi-source information fusion, etc. The applicability and characteristics of these diagnoses are described, and the existing defects and the overall direction of improvement are briefly described Finally, the key technical problems and future directions in the field of power system fault diagnosis are pointed out by combining theory with practice, so as to promote the further development of this field.

The main apple production areas of the Loess Plateau, China limited information on soil and leaf K, Ca, Mg, and micronutrients and their relationships in these orchards. Therefore, we collected soil and leaf samples from the main apple production areas of the Loess Plateau and analyzed them to assess soil and leaf K, Ca, Mg, Cu, Mn, Zn, and Fe as well as to visualize their relationships. The investigated apple orchards in the Loess Plateau exhibited low soil Mn, moderate soil K, Zn, Fe, and high Cu and deficiency of leaf Fe, Moderate of leaf K, Cu, and Zn, high of leaf Ca, Mg, and excessive in leaf Mn. Moreover, soil pH negatively correlated with soil K, Cu, Zn, and Fe and positively related to exchangeable Mg, leaf Mg, and leaf Ca. Exchangeable Ca was negatively related to soil Mg, Cu, Mn, and Fe. Meanwhile, exchangeable K also negative correlation with leaf Mg, indicating the importance of soil pH and exchangeable Ca as an indication of apple produc-tion. In addition, available Zn also negative correlation with leaf Ca and leaf Zn. Soil micronu-trient contents in Shaanxi province trend lower than in other provinces, suggesting that soil Mn and Zn deficiency may be a limiting factor for apple production. Consequently, it is suggested that the soil pH be reduced in the Loess Plateau, replenishing soil organic matter and micronutrients, controlling soil Ca and Mg, and the Loess Plateau must pay attention to controlling K fertilizer application to avoid soil exchangeable cation and enhancing organic fertilizer application to improve soil micronutrients (Zn, Mn, and Fe) are highly necessary and it is necessary to enhance leaf Fe.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year mortality (from 20% to 36%). Considering the high rate of re-hospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

Liver is the sixth most common site of primary malignant tumors, and the third leading cause of cancer death worldwide. Hepatocellular carcinoma is the most common primary liver malignancy and lungs, abdominal lymph nodes and adrenal glands are the most common sites of its metastasis. We present a rare case of an isolated metastasis of a hepatocellular carcinoma in the left mandibular ramus, with regards to its clinical and radiological presentation and with regards to possible routes of the metastatic spread.

Delineating the epidemic of vaccine injury from the coterminous condition long covid is a challenging prospect, but one with many implications not just for treatment, but also has important legal considerations for settlements of vaccine injury. The shared etiological factor of the spike protein in both vaccine injury and long covid make differentiation difficult, and while treatment is largely similar between vaccine injury and long covid, there are important distinctions. Furthermore, diagnostics are important for monitoring treatment progress and assessing the extent of subclinical vaccine injury in population having received a covid-19 vaccine. The development of rigorous diagnostics is an important step towards the recognition of both long covid and vaccine injury, as those suffering these conditions have faced immense challenges in having their conditions recognized, treated, and compensated by insurance companies or national health services.

A diagnosis of typical chronic lymphocytic leukemia (CLL) requires the presence of ≥5000 clonal B-lymphocytes/μL with the coexistence of CD19, CD20, CD5, and CD23 and the restriction of light chain immunoglobulin, and the lack of expression of antigens CD22 and CD79b. Atypical CLL (aCLL) can be distinguished from typical CLL morphologically and immunophenotypically. Atypical CLL cells are defined as prolymphocytes; morphologically, these present as deeply-clefted lymphocytes which are larger than those in typical CLL, with condensed chromatin and without prominent nucleoli. However, current aCLL diagnostics rely more on immunophenotypic characteristics rather than atypical morphology. Immunophenotypically, atypical CLL differs from classic CLL in the lack of expression of one or fewer surface antigens, most commonly CD5 and CD23, and the patient does not meet the criteria for a diagnosis of any other B-cell lymphoid malignancy. Morphologically atypical CLL has more aggressive clinical behavior and worse prognosis than classic CLL. Patients with aCLL are more likely to display markers associated with poor prognosis, including trisomy 12, unmutated IGVH, and CD38 expression compared with classic CLL. However, no standard or commonly-accepted criteria exist for differentiating aCLL from classic CLL and the clinical significance of aCLL is still under debate. This review summarizes the current state of knowledge on the morphological, immunophenotypic and genetic abnormalities of aCLL.

A wide variety of renal neoplasms can have cystic areas. It happens for different reasons: some tumors have an intrinsic cystic architecture, others have a pseudocystic degeneration of necrotic foci or they have cystically dilated renal tubules constrained by stromal neoplastic cells. Clear cell renal cell carcinoma (CCRCC), either solid or cystic, is the most frequent type of renal cancer. While pseudocysts are found in high-grade aggressive CCRCC, cystic growth is associated to low-grade indolent cases. The latter also form through a cyst-dependent molecular pathway and they are more frequent in patients suffering from VHL disease. The differential diagnosis with multilocular cystic renal neoplasm of low malignant potential and clear cell papillary renal cell tumor can be especially hard and it requires a focused macroscopical and microscopical pathological analysis. As every class of renal tumors include cystic forms, a knowledge of criteria for a differential diagnosis is mandatory.

Recently, a database of human piRNAs has been created, which allows studying the binding of many piRNAs to mRNAs of genes involved in many diseases, including cancer. In the present work, we investigated what piRNAs can interact with candidate esophageal squamous cell carcinoma (ESCC) genes. The binding of 480 thousand piRNAs with mRNAs of 66 candidate ESCC genes was studied. Bioinformatic studies found that piRNAs bind only to the mRNAs of nine candidate genes: AURKA, BMP7, GCOM1, ERCC1, MTHFR, SASH1, SIX4, SULT1A1, and TP53. It has been shown that piRNAs can bind to mRNA by overlapping nucleotide sequences in limited 3'UTR and 5'UTR regions called clusters of binding sites (BSs). The existence of clusters of piRNA BSs significantly reduces the proportion of nucleotide sequences of these sites in the mRNA of target genes. Competition between piRNAs occurs for binding to the mRNA of target genes. Individual piRNAs and groups of piRNAs that have separate BSs and clusters of BSs in the mRNAs of two or more candidate genes have been identified in the mRNAs of these genes. This organization of piRNAs BSs indicates the interdependence of the expression of candidate genes through piRNAs. Significant differences in the ability of genes to interact with piRNAs avoid the side effects of piRNAs on genes with the lack of binding of such piRNAs. Individual piRNAs and sets of piRNAs are proposed and recommended for the diagnosis and therapy of ESCC.

Introduction: Austere environments include the wilderness and many lower-and-middle-income countries, many of these facing unrest and war. The access to advanced diagnostic equipment is often unaffordable even if available and is often liable to breakdown. This short review paper examines the options available to medical professionals to undertake clinical and point of care diagnostic testing in resource constrained environments and also illustrates the development of mobile advanced diagnostic equipment. The aim is to provide an overview of the spectrum and functionality of these devices beyond clinical acumen.

Abstract: The EMU(electric multiple units) traction motors are powered by converters. The PWM(pulse width modulation) voltage increases the voltage stress borne by the motor insulation system, making the ITSC(inter-turn short-circuit) fault more prominent. An index based on short-circuit thermal power was proposed in the article to evaluate the non-metallic ITSC faults degree. The apFFT(all phase FFT) time-shift phase difference correction with double Hanning-windows is used to calculate the fundamental frequency of the traction motor's ZSVC（zero se-quence voltage component）, the fundamental amplitudes of ZSVC and three-phase current. The five parameters are used as fault features to train the SVM (support vector machine)fault diagnosis model. The SVM hyper-parameters C and g are optimized by K-CV (K fold cross-validation) and grid search methods. The experimental verification was carried out by the EMU electric traction simulation experimental platform. According to the non-metallic degree index proposed in this article, the experimental samples were divided into three categories, normal, incipient and serious fault samples. The ITSC fault diagnosis accuracy was 100% on the training data set and 93.33 % on the test data set. There was no misclassification between normal and serious ITSC fault samples.

Background: In healthy children, the frequency of anomalous persistence of primitive reflexes (PRs) and craniosacral blocks (CBs) are unknown, as well as their impact on neurodevelopment, behaviour disorders and related consequences. We aim to know the prevalence of anomalous PRs and CBs in apparently healthy children and its relationships with behavior and neurodevelopment anomalies. Methods: Participants (n=120) were evaluated through physical examination to detect PRs and CBs, an ad hoc parent survey to collect perinatal events, and children behavior assessment by teachers using Battelle score. Results: PRs were present in 89.5%. Moro (70.8%), cervical asymmetric (78.3%) and cervical symmetric PRs (67.5%) were the most frequent observed PRs. CBs were found in 83.2%, and the most frequent CBs were dura mater (77.5%) and sphenoid bone (70%) blocks. Moro, cervical asymmetric and cervical symmetric active primitive reflexes are significantly associated to cranial blocks of dura mater, parietal zones, and sphenoid bone sway. Gestational disorders or perinatal complications were associated to a higher frequency of PRs and CBs. The presence of PRs and CBs were associated with abnormal Battelle scores and neurobehavioral problems. Conclusion: Presence of PRs and CBs in children without diagnosed diseases are frequent and related with disturbances in childhood neurodevelopment.

Dry eye disease (DED) is one of the most common eye diseases. There is at least one DED patient in almost every five people. AI-based research methods increasingly become the focus of DED diagnosis research. This study utilizes a systematic review method on DED AI-based diagnosis. 2112 unduplicated records are extracted from Google Scholar, Web of Science (WOS), PubMed, China National Knowledge Infrastructure (CNKI), and Scopus databases. The most contributed countries, institutions, authors, journals, references, and disciplines are recognized. Keyword distribution and hot topics are identified. Popular databases of ophthalmic images, videos, and electronic demographic medical records are discussed. The DED diagnosis, classification, and grading criteria are identified. The major diagnosing methods are clustered, compared, and investigated. Findings show that diagnosing method research could be classified into three categories based on the relationship between AI techniques, which are (1) ground truth and/or comparable standards for AI DED diagnosis (TBUT, S Ⅰ T, TMH, and OSDI), (2) potential methods for AI-based methods have a great advantage(DED detection based on meibometry Images, CASPs, IVCM Images, OCT Images, blink videos and ultrasonic imaging), (3) and the potential direction and supplemented methods for AI-based DED detection (DED detections based on tear osmolarity, proteomic analysis, TCM and demographic information). AI-based approaches based on digital ophthalmologic images play an important role in early screening. Challenges and future perspectives are discussed at the end of this article, academically and practically.

The new NICE guideline for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), published in October 2021, makes significant changes in treatment recommendations. It acknowledges the complexity of this chronic medical condition, which always impacts quality of life and can be profoundly disabling, recognising the prejudice and stigma that people with ME/CFS often experience in the absence of any specific diagnostic test. The guideline outlines steps for accurate diagnosis, recognising post-exertional malaise as a core symptom; importantly, ME/CFS can now be diagnosed after just 3 months in a bid to improve long-term health outcomes. It recommends the need for individual, tailored management by a multi-disciplinary team, ensuring that the wellbeing of the individual is paramount. The guideline makes clear that any programme based on fixed incremental increases in physical activity or exercise, for example graded exercise therapy (GET), should not be offered as a treatment for ME/CFS and emphasises that cognitive behavioural therapy (CBT) should only be offered as a supportive intervention. Because of the rigorous methodology required by NICE Committee review and the inclusion of the testimony of people with lived experience as committee members, this guideline will influence the future diagnosis and management of ME/CFS in the UK and beyond.

The aim of the current study was to determine the relation between subclinical mastitis and rumination behavior registered with an online sensor system. According to the results of the general clinical examination of 650 milking cows, 10 cows with subclinical mastitis (SCM) and 10 clinical healthy cows (HG) were selected (without clinical signs of any diseases). Rumination behavior biomarkers were registered with RumiWatch noseband sensor (RWS; ITIN + HOCH GmbH, Fütterungstechnik, Liestal, Switzerland). Sensors were implanted on the first day after calving. Data from the RWS from 13th days before the diagnosis and 13 days after diagnosis of SCM were used to compare with HG data during the same period. The healthy cows were monitored during the same days as the SCM cows.

One of the most dangerous diseases that threaten people is Cancer. Cancer if diagnosed in earlier stages can be eradicated with its life threatening consequences. In addition, accuracy in prediction plays a major role. Hence, developing a reliable model that contributes much towards the medical community in early diagnosis of Biopsy images with perfect accuracy come to the scenario. The article aims towards development of better predictive models using multi-variate data and high-resolution diagnostic tools in clinical cancer research. This paper proposes the social spider optimization (SSO) algorithm tuned neural network to classify microscopic biopsy images of cancer. The significance of the proposed model relies on the effective tuning of the weights of the NN classifier by the SSO algorithm. The performance of the proposed strategy is analysed with the performance metrics, such as accuracy, sensitivity, specificity, and MCC measures, and are attained to be 95.9181%, 94.2515%, 97.125%, and 97.68% respectively, which shows the effectiveness of the proposed method in effective cancer disease diagnosis.

Dirofilaria immitis infection is one of the most severe parasitic diseases of dogs. Prevention is achieved by the administration of drugs containing macrocyclic lactones (MLs). These products are very safe and highly effective, targeting the third and fourth larval stages (L3, L4) of the parasite. Until 2011, claims of ineffectiveness of MLs, reported as “Lack of Efficacy” (LOE), were generally attributed to owners’ non-compliance, or other reason for inadequate preventative coverage. There was solid argumentation that a resistance problem is not likely to occur because of i) the great extent of refugia, ii) the complexity of resistance development to MLs, and iii) the possible big number of genes involved in resistance selection. Nevertheless, today it is unequivocally proven that ML resistant D. immitis strains exist, at least in the Lower Mississippi region, USA. Accordingly, tools have been developed, to evaluate and confirm the susceptibility status of D. immitis strains. A simple, in-clinic, microfilariae suppression test, 14-28 days after ML administration, and a “decision tree” (algorithm), including compliance and preventatives’ purchase history, and testing gaps, may be applied for assessing any resistant nature of the parasite. On the molecular level, specific SNPs may be used as markers of ML resistance, offering a basis for validation of clinically suspected resistant strains. In Europe, no LOE/resistance claims have been reported so far, and the existing conditions (stray dogs, rich wildlife, majority of owned dogs not on preventive MLs treatment) do not favor selection pressure on the parasites. Considering the genetic basis of resistance and the epizootiological characteristics of D. immitis, ML resistance neither establishes easily nor spreads quickly, a fact confirmed by the current known dispersion of the problem, which is limited. Nevertheless, ML resistance may propagate from an initial geographical point, via animal and vector mobility, to other regions, while it can also emerge as an independent evolutionary process in a new area. For these reasons and considering the current chemoprophylaxis recommendations and increasing use of ML endectoparasiticides as a potential selection pressure, it is important to remain vigilant for timely detection of any ML LOE/resistance, in all continents where D. immitis is enzootic.

Background. A previous study demonstrated the performance of the Salivette® (SARSTEDT, Numbrecht, Germany) as a homogeneous saliva collection system to diagnose COVID-19 by RT-qPCR, notably for symptomatic and asymptomatic patients. However, for convalescent patients, the corroboration of molecular detection of SARS-CoV-2 in paired nasopharyngeal swabs (NPS) and saliva samples was unsatisfactory. Objectives. The aim of the present work was to assess the concordance level of SARS-CoV-2 detection between paired sampling of NPSs and saliva collected with Salivette® at two time points, with ten days of interval. Results. A total of 319 paired samples from 145 outpatients (OP) and 51 healthcare workers (HW) were collected. Due to significant waiting rate at hospital, most of the patients ate and/or drank in waiting their turn. Consequently, a mouth washing was systematically proposed prior saliva collection. None of the HW were diagnosed SARS-CoV-2 positive using NPS or saliva specimens at both time points (n=95) by RT-qPCR. The virus was detected in 56.3% (n=126/224) of the NPS samples from OP, but solely 26.8% (n=60/224) of the paired saliva specimens. The detection of the internal cellular control, the human RNase P, in more than 98% of the saliva samples, underlined that the low sensitivity of saliva specimens (45.2%) for SARS-CoV-2 detection was not attributed to an improper saliva sample storing or RNA extraction. Conclusions. Then, the mouth washing decreased viral load of buccal cavity conducting to impairment of SARS-CoV-2 detection. Viral loads in saliva neo-produced appeared insufficient for molecular detection of SARS-CoV-2. At the time that saliva tests could be a rapid, simple and noninvasive strategy to assess on large scale schooled children in France, the determination of the performance of saliva collection become imperative to standardize procedures.

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.

Myocarditis is the form of an inflammation of the middle layer of the heart wall which is caused by a viral infection and can affect the heart muscle and its electrical system. It has remained as one of the most challenging diagnoses in cardiology. Myocardial is the prime cause of unexpected death in approximately 20% of adults less than 40 years of age. Cardiac MRI (CMR) has been considered as a noninvasive and golden standard diagnostic tool for suspected myocarditis and plays an indispensable role in diagnosing various cardiac diseases. However, the performance of CMR is heavily dependent on the clinical presentation and non-specific features such as chest pain, arrhythmia, and heart failure. Besides, other imaging factors like artifacts, technical errors, pulse sequence, acquisition parameters, contrast agent dose, and more importantly qualitatively visual interpretation can affect the result of the diagnosis. This paper introduces a new deep learning-based model called Convolutional Neural Network-Clustering (CNN-KCL) to diagnose the Myocarditis. The hybrid CNN-KCL method performs the early and accurate diagnosis of Myocarditis. To the best-of-our-knowledge, a Convolutional neural network has never been used before for the diagnosis of Myocarditis. In this study, we used 47 subjects to diagnose myocarditis patients from Tehran's Omid Hospital. The total number of data examined is 10425. Our results demonstrate that CNN-KCL achieves 92.3% in terms of diagnosis myocarditis prediction accuracy which is significantly better than those reported in previous studies.

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread so rapidly and severely affected the people of almost every country in the world. The highly contagious nature of this virus makes it difficult to take control of the present pandemic situation. With no specific treatment available, the coronavirus disease 2019 (COVID-19) presents a threat to people of all ages including the elderly people and people with other medical complications as a vulnerable group to this disease. Better understanding of viral pathogenesis, appropriate preventive measures, early diagnosis and supportive treatments of the infected patients are now the general solutions to fight against this viral transmission. But, as an emerging disease, most about it remains still poorly understood. This article holds an overview on the origin and structure, pathogenesis, diagnosis and possible therapeutic options for the causative agent, SARS-CoV-2 and disease, COVID-19. However, few therapeutic options, laboratory experiments and other strategies proposed here need to be further clinically tested.

Most diagnostic tests for tuberculosis (TB) rely on sputum samples, which are difficult to obtain and have low sensitivity in immunocompromised patients, patients with disseminated TB, and children, delaying treatment initiation. The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of TB at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker which can be detected in urine, an easily collected sample. This review discusses the characteristics of LAM as a biomarker, describes the performance of first-generation urine LAM tests and reasons for slow uptake, and presents considerations for developing the next-generation of more sensitive and impactful tests. Next-generation urine LAM tests have the potential to reach adult and pediatric patients regardless of HIV status or site of infection and facilitate global TB control. Implementation and scale-up of existing LAM tests and development of next-generation assays should be prioritized.

Background: Malignant pleural mesothelioma (MPM) is an atypical, belligerent tumor that matures into cancer in the pleura, a stratum of tissue bordering the lungs. Pleural mesothelioma is a common type of mesothelioma that accounts for about 75 percent of all mesothelioma diagnosed yearly in the United States. Diagnosis of mesothelioma takes several months and is expensive. Given the difficulty of diagnosing MPM, early identification is crucial for patient survival. Our study implements artificial intelligence and recommends the best fit model for early diagnosis and prognosis of MPM. Method: We retrospectively retrieved patient’s medical reports generated by Dicle University, Turkey and implemented multi-layered perceptron (MLP), voted perceptron (VP), Clojure classifier (CC), kernel logistic regression (KLR), stochastic gradient decent SGD), adaptive boosting (AdaBoost), Hoeffding tree (VFDT), and primal estimated sub-gradient solver for support vector machine (s-Pegasos). We evaluated the models, compared and tested using paired T-test (corrected) at 0.05 significance based on their respective classification accuracy, f-measure, precision, recall, root mean squared error, receivers characteristic curve (ROC), and precision-recall curve (PRC). Results: In phase-1 SGD, AdaBoost.M1, KLR, MLP, VFDT generates optimal results with the highest possible performance measures. In phase-2, AdaBoost with a classification accuracy of 71.29% outperformed all other algorithms. C-reactive protein, platelet count, duration of symptoms, gender, and pleural protein were found to be the most relevant predictors that can prognosticate mesothelioma. Conclusion: This study confirms that data obtained from biopsy and imagining tests are strong predictors of mesothelioma but are associated with high cost, however, can identify mesothelioma with optimal accuracy. Predictive analytics without using biopsy results can diagnose mesothelioma with acceptable accuracy. Implementation of phase-2 followed by phase-1 can address diagnosis expenses and maximize disease prognosis. Additionally, results indicate improved MPM diagnosis using AI methods dependent upon the specific application.

Liver cirrhosis is a chronic disease that is characterized by the presence of fibrosis and regeneration of nodules in the liver whose consequences are the development of portal hypertension and liver failure. Cirrhosis arises from a wide variety of chronic diseases, which progresses slowly after years or decades. Liver cirrhosis is a public health problem. It is usually associated with viral hepatitis, consumption of alcohol, metabolic syndrome, autoimmune processes, storage diseases, toxic substances, and medications. Cirrhosis is the fourteenth most common cause of death in adults throughout the world, the fourth in Europe and the ninth in the United States. The prevalence of this disease is underestimated because it is symptomatic it is not diagnosed in initial stages, and it usually goes to the decompensated stage at a rate of 5 to 7% per year. We review here the epidemiology, pathophysiology, etiology, and diagnosis of liver cirrhosis.

The aim of this study was to examine pathologic complete response (pCR) and overall survival (OS) of patients diagnosed with non-metastatic inflammatory breast cancer (IBC). A total of N=8,550 cases undergoing surgery were identified between 2004-2013, using the National Cancer Database (NCDB). Patients were grouped into 4 biologic subtypes (HR+/HER2-, HR+/HER2+, HR-/HER2+, HR-/HER2-). The median age at diagnosis was 56 years. On average, women were followed for 3.7 years [interquartile range=3.0]. The majority were white (80%), had private health insurance (50%), and presented with poorly differentiated tumors (57%). Approximately 46% of the cancers were >5cm. Most patients underwent mastectomy (94%) and received radiotherapy (71%). Differences by biologic subtypes were observed for grade, lymph node invasion, race, and tumor size (p<.0001). Compared with non-pCR (54%), patients experiencing pCR had superior 5-year survival (77%) (p<.0001). Survival was poor for triple-negative (TN) tumors (37%) vs. other biologic subtypes (60%) (p<.0001). On multivariable analysis, TN-IBC, positive margins, and not receiving either chemotherapy, hormonal therapy or radiotherapy were independently associated with poor 5-year survival (p<.0001). In this large multicentric analysis of IBC, categorized by biologic subtypes, we observed significant differential tumor, patient and treatment characteristics, and OS.

For planetary gear has the characteristics of small volume, light weight and large transmission ratio, it is widely used in high speed and high power mechanical system. Poor working conditions result in frequent failures of planetary gear. A method is proposed for diagnosing faults in planetary gear based on permutation entropy of Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) Adaptive Neuro-fuzzy Inference System (ANFIS) in this paper. The original signal is decomposed into 6 intrinsic mode functions (IMF) and residual components by CEEMDAN. Since the IMF contains the main characteristic information of planetary gear faults, time complexity of IMFs are reflected by permutation entropies to quantify the fault features. The permutation entropies of each IMF component are defined as the input of ANFIS, and its parameters and membership functions are adaptively adjusted according to training samples. Finally, the fuzzy inference rules are determined, and the optimal ANFIS is obtained. The overall recognition rate of the test sample used for ANFIS is 90.75%, and the recognition rate of gear with one missing tooth is relatively high. The recognition rates of different fault gears based on the method can also achieve better results. Therefore, the proposed method can be applied to planetary gear fault diagnosis effectively.

Background: Cytomegalovirus (CMV) infection has been associated with venous thromboembolism (VTE) and acute coronary syndromes (ACS). Methods: A retrospective study was conducted within the OSF HealthCare System in Peoria, Illinois. The objectives were to determine the incidence of acute VTE and ACS within one year of CMV testing. The “study group” included patients with positive CMV IgM or positive CMV Polymerase Chain Reaction (PCR). The “seropositive control” group included patients with positive CMV IgG and negative IgM. The “seronegative control” group included patients with negative CMV IgG and IgM, or negative PCR. Results: Within one year of CMV infection, 38 of 379 patients (10.0%) developed VTE in the study group compared to 41 of 1334 patients (3.1%) in the seropositive control and 37 of 1249 (3.0%) in the seronegative control. Adjusting for age and gender, both control groups were less likely to have VTE than the study group within one year (Seropositive Control: OR = 0.3, 95% CI 0.2-0.5, p <0.0001; Seronegative Control: OR = 0.4, 95% CI 0.2-0.6, p <0.0001). ACS was more likely to occur in the study group, with incidence of 7.7% compared to 4.7% (p <0.0001) in the seropositive control and 1.9% (p <0.0001) in the seronegative control. Adjusting for age and gender, the seronegative control was less likely to develop ACS than the study group within one year (OR = 0.4, 95% CI 0.2-0.7, p = 0.003). Conclusions: This retrospective study demonstrates that CMV infection may be a significant risk factor for VTE and ACS.

In this work, a hybrid component Fault Detection and Diagnosis (FDD) approach for industrial sensor systems is established and analyzed, to provide a hybrid schema that combines the advantages and eliminates the drawbacks of both model-based and data-driven methods of diagnosis. Moreover, it shines the light on a new utilization of Random Forest (RF) together with model-based diagnosis, beyond its ordinary data-driven application. RF is trained and hyperparameter tuned using three-fold cross validation over a random grid of parameters using random search, to finally generate diagnostic graphs as the dynamic, data-driven part of this system. This is followed by translating those graphs into model-based rules in the form of if-else statements, SQL queries or semantic queries such as SPARQL, in order to feed the dynamic rules into a structured model essential for further diagnosis. The RF hyperparameters are consistently updated online using the newly generated sensor data to maintain the dynamicity and accuracy of the generated graphs and rules thereafter. The architecture of the proposed method is demonstrated in a comprehensive manner, and the dynamic rules extraction phase is applied using a case study on condition monitoring of a hydraulic test rig using time-series multivariate sensor readings.

In this work, A hybrid component Fault Detection and Diagnosis (FDD) approach for industrial sensor systems is established and analyzed, to provide a hybrid schema that combines the advantages and eliminates the drawbacks of both model-based and data-driven methods of diagnosis. Moreover, spotting the light on a new utilization of Random Forest (RF) together with model-based diagnosis, beyond its ordinary data-driven application. RF is trained and hyperparameter tuned using 3-fold cross-validation over a random grid of parameters using random search, to finally generate diagnostic graphs as the dynamic, data-driven part of this system. Followed by translating those graphs into model-based rules in the form of if-else statements, SQL queries or semantic queries such as SPARQL, in order to feed the dynamic rules into a structured model essential for further diagnosis. The RF hyperparameters are consistently updated online using the newly generated sensor data, in order to maintain the dynamicity and accuracy of the generated graphs and rules thereafter. The architecture of the proposed method is demonstrated in a comprehensive manner, as well as the dynamic rules extraction phase is applied using a case study on condition monitoring of a hydraulic test rig using time series multivariate sensor readings.

Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they caused requires the sampling of body fluids (blood, lymph, peritoneal fluid, cerebrospinal fluid, etc.) or organ biopsies (bone marrow, spleen, etc.), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, Google. The information of each selected article (n=333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on Human African Trypanosomiasis and a the absence on animal Trypanosomiasis. Among the collected data high heterogeneity in terms of the I² statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigen for leishmaniasis and Chagas disease. Data on conjunctival swab can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristle showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristle for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites.

Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To investigate this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis using summary statistics of genome-wide association studies (GWAS) from 412 gut microbiome traits (N = 7,738) and GWAS studies from seven sleep-associated traits (N = 345,552 to 386577). We employed multiple MR methods to assess causality, with Inverse Variance Weighted (IVW) as the primary method. We further applied Cochran’s Q statistical analysis, MR-Egger intercept, and MR-PRESSO for heterogeneity and pleiotropy assessment, alongside a Bonferroni correction ((P

The growth of the wind power sector has been marked by environmental, economic, and political drivers. Its starring role is also visible in the emergence of the so-called “green jobs”. Notwithstanding, its evolution ought not to compromise issues related to occupational risks. This exploratory study examines psychosocial risks in the operation and maintenance of onshore wind turbines in a leading Portuguese company. We conducted interviews with main stakeholders (Human Resources, OHS professionals, and team leaders); developed an “activity diary” for the operation and maintenance technicians to describe their activity and perceived impacts on health, complemented with collective interviews; and applied the Work and Health Survey. The results revealed particular risks and health impacts: working under adverse weather conditions; working at heights and in confined spaces; spending long work hours inside of the nacelles to achieve an optimum balance between favorable wind slots to intervene and avoiding additional trips up and down the wind turbines without lifts (70m-120m); and the feeling of early ageing. At a time when these workers are striving for recognition of their profession as a “rapid wear profession”, it is a key moment to discuss these results to guarantee sustainable conditions for future generations of workers.

Electroencephalography (EEG) enabled earbuds represent a promising frontier in evaluating brain activity beyond traditional laboratory settings. However, these devices need more comprehensive characterization before widespread health related usage. A toolbox was developed to facilitate and expand the assessment of ear-EEG devices. The first component of this toolbox is a desktop application (“EaR-P Lab”) that integrates EEG validation paradigms. This application is designed to be used with EEG amplifiers compatible with the Lab Streaming Layer (LSL) protocol. The second element of the toolbox introduces an adaptation of the phantom testing concept, to the domain of ear-EEG by using 3D ear scans of the tested individuals, allowing controlled assessment of ear-EEG devices. The EEG paradigms were validated for scalp acquisitions and applied on ear-EEG measurements, under wet ear electrode conditions. The ear-EEG phantom was successful in measuring useful metrics in EEG system characterization, highlighting performance differences within the electrodes on the tested earpieces. This knowledge was factored in to select an optimal electrode reference which resulted in increased response power on the auditory steady-state response (ASSR). Through this work, an ear-EEG evaluation toolkit is made available with the intention to enable future and systematic assessment of novel ear-EEG devices from the hardware to the neural signals.

Better understanding of the quality of life among nursing home residents with dementia is im-portant for developing interventions. The objectives of this cross-sectional study were to examine factors associated with poor health-related quality of life in older adults with dementia living in nursing homes in Hanoi, Vietnam. In-person interviews were conducted with 140 adults 60 years and older with dementia and information about their quality of life was obtained using the Quality of Life in Alzheimer’s Disease scale (QOL-AD). A number of sociodemographic and clinical factors associated with poor health-related quality of life (lowest tertile) were assessed through the results of physical tests, interviews with nursing home staff, and review of medical records. The average age of the study sample was 78.3 years, 65% were women, and their av-erage QOL-AD total score was 27.3 (SD = 4.4). Malnutrition, total dependence in activities of daily living, and urinary incontinence were associated with poor quality of life after controlling for multiple potentially confounding factors. Our findings show that Vietnamese nursing home residents with dementia have a moderate quality of life and interventions based on comprehen-sive geriatric assessment remain needed to modify risk factors associated with poor health-related quality of life.

The world is facing an energy crisis. Governments are seeking to provide universal energy access and guarantee energy security while trying to mitigate climate change. One possible solution is energy transitions towards low carbon energy systems. Among other things (physical infrastructure, public policy and regulatory enablers and knowledge and capacities) changes in the energy systems require a well informed and participative citizenship. Within this context the concept of energy literacy appears. Energy literacy is the understanding of how energy is generated, transported, stored, distributed and used, awareness about its environmental and social impacts and the knowledge to use it efficiently in the different sectors of the economy. This paper provides a systematic literature review in the Web of Science’s Core Collection. Most of the work done around energy literacy addresses its evaluation among different groups, particularly students at different levels, and the construction, application and evaluation of tools for improving energy literacy. Other frequently studied issues are the influence of energy literacy in decision making, its drivers and conceptual research about the topic. Energy enables citizens to effectively contribute to energy efficiency and sustainable development, nevertheless energy literacy is not strongly correlated to energy consumption habits.

Abstract: Sarcopenia poses a significant challenge to public health and can severely impact the quality of life of aging populations. Despite extensive efforts to study muscle degeneration using traditional animal models, there is still a lack of effective diagnostic tools, precise biomarkers, and treatments for sarcopenia. Zebrafish models have emerged as powerful tools in biomedical research, providing unique insights into age-related muscle disorders like sarcopenia. The advantages of using zebrafish models include their rapid growth outside of the embryo, optical transparency during early developmental stages, high reproductive potential, ease of husbandry, compact size, and genetic tractability. By deepening our understanding of the molecular processes underlying sarcopenia, we may develop novel diagnostic tools and effective treatments that can improve the lives of aging individuals affected by this condition. This review aims to explore the unique advantages of zebrafish as a model for sarcopenia research, highlight recent breakthroughs, outline potential avenues for future investigations, and emphasize the distinctive contributions that zebrafish models offer. Our research endeavors to contribute significantly to addressing the urgent need for practical solutions to the impact of sarcopenia on aging populations, ultimately striving to enhance the quality of life for individuals affected by this condition.

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness world-wide. We recently reported that polyethylene glycol (PEG) can activate the alternative pathway of the complement system and induce choroidal neovascularization (CNV) in mice. Currently, no other investigator has demonstrated CNV after PEG injection in the mouse eye. The aim of this article is twofold: we review the histologic changes in mouse retina and retinal pigmented epithelium (RPE) after treatment with PEG, and we summarize a model of wet and dry AMD pathogenesis in mice through subretinal PEG treatment of RPE cells and retinal layers. We injected (subretinal) male C57BL/6 mice with 2 μL of solution containing 0.5 mg and 1.0 mg of PEG or PBS in control groups. Eyes were harvested at day 1, 3 and 5 after injection and processed for analysis. Sections were immunohistochemically stained for complement component C3, mem-brane attack complex (MAC), and cytokeratin 18. Light and laser confocal microscopy was used for image capturing. PEG increased deposition of C3 and MAC on RPE cells and on all retinal layers after 1.0 mg injection. PEG induced loss of cellular contacts between RPE cells and migration of RPE cells in the subretinal space at day 1 after PEG injection. After 0.5 mg PEG injection, increased size of RPE cells was detected at day 3 and 5. Apoptotic bodies were observed in outer nuclear layer at day 3 and 5 after 0.5 mg PEG treatment. RPE cells with dark cytoplasm and condensed chromatin were observed. Higher doses of PEG induce CNV, encouraged RPE cell proliferation and death, and damage photoreceptors in mice. This simple and fast model may be useful to explore the pathogenesis of both dry and wet AMD.

Plants respond to drought by major reprogramming of gene expression enabling the plant to survive this threatening environmental condition. One major upstream signal inducing this multifaceted process is the phytohormone abscisic acid (ABA). In this report, we investigate the drought response in barley plants (Hordeum vulgare, cv. Morex) at both epigenome and transcriptome levels. Leaves of barley plants after 10 days of drought treatment, when soil water content was decreased by about 40%, were compared to well-watered controls. Due to the drought treatment, chlorophyll content and photosystem II-efficiency were decreased by about 10% and some known drought-related genes were already induced. Global ChIPseq analyses were used to identify genes where histones 3 associated with promoter or gene body were modified with euchromatic K4 trimethylation or K9 acetylation during drought. Using stringent exclusion criteria, 129 genes loaded with H3K4me3 and 2008 genes loaded with H3K9ac in response to drought were identified, indicating that H3K9 acetylation reacts to drought more sensitive than H3K4 trimethylation. Comparison with differentially expressed genes enabled to identify those genes, which are loaded with the euchromatic marks and are induced in response to the drought treatment. The results show that a major part of these genes is involved in ABA-signaling and related pathways. Intriguingly, two members of the protein phosphatase 2C family (PP2Cs), which are involved in the central regulatory machinery of ABA signaling, were also identified by this approach.

The durability of ecological concrete in a marine environment was studied. Specimens of a six-year-old submerged ecological concrete from a breakwater located in the East Mediterranean sea were analyzed for their biological carbonate deposition cover, chloride effective diffusion, carbonation, and mineralogy. About 57% of the surface was found to be covered by biogenic-deposited carbonates. The effective chloride diffusion coefficient and the carbonation rate were found to be reduced proportionally to the biogenic-carbonate cover. Most of the aluminates were found in non-crystalline minerals. No evidence of a sulfate attack was found.

In northern Thailand, the problem of small particulate matter happens every year, with the pri-mary source being agricultural weed burning and wildfire. The tourism industry is strongly impacted and has been the spotlight for the past few years. Thus, the study aims to investigate the effect of small particulate matter on tourism and related SMEs in Chiang Mai, Thailand. The data was collected from 286 entrepreneurs in the tourism and related SMEs sectors. The data was analyzed using data mining and association rule techniques. The study revealed that small particulate matter has a considerable impact on customer factors, especially the number of customers has decreased. Operational factors and prod-uct/service factors are also affected by the dust in the form of adjustments to keep the business running and the protection of the health of employees and customers. Certainly, financial factors are affected by the small particulate matter situation, both lower revenues and higher costs.

Abstract Background The number of immune-related endocrine dysfunctions (irEDs) has concurrently increased with the widespread use of immunotherapy in clinical practice and further expansion of the approved indications for immune checkpoint inhibitor (ICI) combinations using different modalities of anti-cancer treatment. Method A retrospective analysis was conducted on consecutive patients >18 years of age with advanced solid malignancies who had received at least one dose of anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies between January 2014 and December 2019 at a Hong Kong university hospital. Patients were reviewed for up to two months after the last administration of an ICI. The types, onset times and grades of irEDs, including hypothyroidism, hyperthyroidism, adrenal insufficiency and immune-related diabetes mellitus, were recorded. Factors associated with irEDs were identified using multivariate analysis. Result A total of 953 patients (male: 603, 64.0%; median age: 62.0 years) received ICIs during the study period. Of these, 580 patients (60.9%) used ICI-alone, 132 (13.9%) used dual-ICI, 187 (19.6%) used an ICI combined with chemotherapy (chemo+ICI), and 54 (5.70%) used immunotherapy with a targeted agent (targeted+ICI). A significantly higher proportion of patients using targeted+ICI had irEDs and hypothyroidism; in contrast, a higher proportion of patients using dual-ICI had adrenal insufficiency. There was no significant difference in the incidence of irED between the younger (<65 years) and older (>65 years) patients. Using logistic regression, only treatment type was significantly associated with irEDs. Notably, older patients had a higher risk of having immune-related diabetes mellitus. Conclusions This large, real-world cohort demonstrates that combining ICI with targeted therapy has a higher risk of overall irED and hypothyroidism. Immunotherapy is safe and well-tolerated regardless of age, but close monitoring of fasting glucose is needed in older populations.

With a highly efficient optical absorption capability, bismuth selenide (Bi2Se3) nanomaterial can be used as an outstanding photothermal agent for anti-tumor treatment and shows promise in the field of nanotechnology-based biomedicine. However, little research has been done on the relevant mechanism underlying the photothermal killing effect of Bi2Se3 nanomaterial. Herein, the photothermal effects of Bi2Se3 nanoparticles on A549 cells were explored with emphasis put on autophagy. Firstly, we characterized the structure and physicochemical property of the synthesized Bi2Se3 and confirmed their excellent photothermal conversion efficiency (35.72%), photostability, biocompatibility and ability of photothermal killing on A549 cells. Enhanced autophagy was detected in Bi2Se3-exposed cells under an 808 nm laser. Consistently, an elevated expression ratio of LC3-II to LC3-I, a marker of autophagy occurrence, was induced in Bi2Se3-exposed cells upon NIR irradiation. Meanwhile, the expression of cleaved-PARP was increased in the irradiated cells dependently on the exposure concentrations of Bi2Se3 nanoparticles. Pharmacological inhibition of autophagy by 3-methyladenine (3-MA) further strengthened the photothermal killing effect of Bi2Se3. Meanwhile, stress-related signaling pathways including p38 and SAPK/JNK were activated coupled with the attenuated PI3K/Akt signaling. Our study figures out that autophagy and the activation of stress-related signaling pathways were involved in the photothermal killing of cancerous cells by Bi2Se3, which provides a more understanding of photothermal nanomaterials.

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

Emotional dysfunction, including flat affect and emotional perception deficits, is a specific symptom of schizophrenia disorder. We used a modified multimodal odd-ball paradigm with fearful facial expressions accompanied by congruent and non-congruent sounds to investigate the impairment of emotional perception and reaction to other people's emotions. We analyzed subjective assessments and ERP data for emotionally charging congruent and non-congruent stimuli in patients with schizophrenia and healthy peers. The results showed the deficit of multimodal perception of fearful stimuli in patients with schizophrenia compared to healthy controls. The amplitude of N50 was significantly higher in subjects of the control group for non-congruent stimuli than congruent and did not differ in patients with schizophrenia. The dynamics of P100 and N200 components confirmed the impaired sensory gating in patients with schizophrenia. The lower amplitude of P3a could be associated with deficits in verbal memory and attention, less emotional arousal, or incorrect interpretation of emotional valence as specific features of patients. The difficulties in identifying the incoherence of facial and audial components of emotional expression could be significant in understanding the psychopathology of schizophrenia.

Daphne wolongensis described on the basis of a few known individuals was investigated in the wild, in Baoxing Valey, Sechuan. Its status of valid species was verified morphologically and genetically. Three newly found populations were compared to the closely related species Daphne retusa, D. tangutica, D. longilobata, D. acutiloba, D. sureil, to clones available in cultivation and selected cultivars. The high bootstrap values indicate a good level of genetic differentiation between each of the studied species. The hypothesis whether D. wolongensis is a hybridogenous species was rejected, it is a well-defined independent species. Based on morphological and genetic data, it seems likely that another species, D. limprichtii can be a mountain form of D. tangutica. Variability of populations in Wolong gives a good opportunity to select genotypes with a higher or better performance of combination of traits. From 51samples collected in Wolong it was possible to select the top ten different types as genetic resources for breeding. Daphne wolongensis, in the visited sites of Wolong area, occupies less than 1 km2. Together with isolated finds, the number of found individuals is less than 500 and the area is not larger than 10 km2, thus it falls to the IUCN category of “Critically Endangered” plants.

Introduction: Osteoarthritis (OA) and age-related degeneration (ARD) are stimulants for the development of the fabella in the knee joint. This meta-analysis updates previous studies and reviews on the prevalence of the fabella in OA or ARD knee joints. In addition, it provides a quantitative estimation of the fabellar prevalence in knees having OA and ARD. Methodology: Twenty studies comprising of data from 11,056 knee joints were included in the analysis, consisting of 6,819 Knees of OA subjects (including those with age more than 40 years) and 4,237 knees of non-OA subjects (including less than 40years) knees, respectively. 2,434 knees had fabellae present in OA subjects (including more than 40years), and 844 fabellae were present in non-OA subjects (including less than 40years). The Odds and Risk Ratios were calculated. Sensitivity analysis and cumulative analysis were conducted to assess the robustness of the findings. Results: Prevalence of fabella was found to be higher in OA knees, where the Risk Ratio of developing fabella was 2.50 (2.07-3.01). Compared with this, the Risk Ratio for the incidence of fabella in OA with ARD knee was 1.84 (1.66-2.03). The bilateral occurrence of fabella was more common than unilateral. The risk of developing fabella in individuals aged less than forty-year was 63% less than individuals aged more than forty years. Conclusion: OA and ARD would increase the prevalence of fabella by 84%, thus acting as stimulants and risk factors for ossified fabella.