Miracle-dz/UniFAR-FTUs huggingface dataset:
Migraine Aura: Pathophysiology, Mimics, and Treatment Options

Abstract Recent insights into the clinical presentation and pathophysiology of migraine aura have paved the way for new treatments for this common but frequently debilitating condition. Marked efflux of cellular potassium and glutamate contributes to the cortical spreading depression that forms the electrophysiological basis of migraine aura phenomena. Secondary vascular perturbations also contribute to the various symptoms of a migraine attack. Calcitonin gene-related peptide (CGRP) plays a key role in many of these steps, and a growing class of CGRP-antagonists have emerged as a novel, efficacious preventative therapy. It is still not fully understood why a preponderance of migraine aura symptoms is visual, and this issue is an active area of research. In addition, the pathophysiological changes responsible for visual snow syndrome are under investigation. Before diagnosing a patient with migraine aura, it is important to consider the differential diagnosis of transient visual phenomena, with attention to clinical features that may suggest conditions such as retinal disorders, transient ischemic attack, or occipital epilepsy.
Response to Multiple Stressors: Enhanced Tolerance of Neoseiulus barkeri Hughes (Acari: Phytoseiidae) to Heat and Desiccation Stress through Acclimation

Organisms are always confronted with multiple stressors simultaneously. Combinations of stressors, rather than single stressor, may be more appropriate in evaluating the stress they experience. N. barkeri is one of predatory mite species that are commercialized for controlling spider mites. However, their biological control efficiency was often reduced because of high temperature and desiccation in summer. To understand how to improve the tolerance of N. barkeri to combined heat and desiccation stress, we pre-exposed the adult female of N. barkeri to high temperature, desiccation and high temperature × desiccation stress for acclimation. After proper recovery time, mites were subjected to high temperature × desiccation stress again to detect the acclimation effects. The results are as follows: (1) No decrease in mortality rate were observed under high temperature × desiccation stress after heat acclimation. Instead, it increased significantly with acclimation temperature and time. (2) Dehydration acclimation both at 25 °C and high temperatures reduced mortality rate under high temperature × desiccation stress. Mortality rate was only significantly correlated with the amount of water loss, but not with temperature or water loss rate in acclimation, suggesting the increased tolerance is related to dehydration stress rather than heat stress. Among all acclimations, chronic dehydration at 25 °C, 50% relative humidity were the most effective treatment. This study indicated dehydration acclimation is effective to enhance tolerance of N. barkeri to combined heat and desiccation stress, which can improve the efficiency of biological control under multiple stressors.
Inhibiting α5 Subunit-Containing γ-Aminobutyric Acid Type A Receptors Attenuates Cognitive Deficits After Traumatic Brain Injury.

OBJECTIVES Cognitive deficits after traumatic brain injury are a leading cause of disability worldwide, yet no effective pharmacologic treatments exist to improve cognition. Traumatic brain injury increases proinflammatory cytokines, which trigger excess function of α5 subunit-containing γ-aminobutyric acid type A receptors. In several models of brain injury, drugs that inhibit α5 subunit-containing γ-aminobutyric acid type A receptor function improve cognitive performance. Thus, we postulated that inhibiting α5 subunit-containing γ-aminobutyric acid type A receptors would improve cognitive performance after traumatic brain injury. In addition, because traumatic brain injury reduces long-term potentiation in the hippocampus, a cellular correlate of memory, we studied whether inhibition of α5 subunit-containing γ-aminobutyric acid type A receptors attenuated deficits in long-term potentiation after traumatic brain injury. DESIGN Experimental animal study. SETTING Research laboratory. SUBJECTS Adult male mice and hippocampal brain slices. INTERVENTIONS Anesthetized mice were subjected to traumatic brain injury with a closed-head, free-weight drop method. One week later, the mice were treated with L-655,708 (0.5 mg/kg), an inhibitor that is selective for α5 subunit-containing γ-aminobutyric acid type A receptors, 30 minutes before undergoing behavioral testing. Problem-solving abilities were assessed using the puzzle box assay, and memory performance was studied with novel object recognition and object place recognition assays. In addition, hippocampal slices were prepared 1 week after traumatic brain injury, and long-term potentiation was studied using field recordings in the cornu Ammonis 1 region of slices that were perfused with L-655,708 (100 nM). MEASUREMENTS AND MAIN RESULTS Traumatic brain injury increased the time required to solve difficult but not simple tasks in the puzzle box assay and impaired memory in the novel object recognition and object place recognition assays. L-655,708 improved both problem solving and memory in the traumatic brain injury mice. Traumatic brain injury reduced long-term potentiation in the hippocampal slices, and L-655,708 attenuated this reduction. CONCLUSIONS Pharmacologic inhibition of α5 subunit-containing γ-aminobutyric acid type A receptors attenuated cognitive deficits after traumatic brain injury and enhanced synaptic plasticity in hippocampal slices. Collectively, these results suggest that α5 subunit-containing γ-aminobutyric acid type A receptors are novel targets for pharmacologic treatment of traumatic brain injury-induced persistent cognitive deficits.
The molecular basis for current targets of NASH therapies

ABSTRACT Introduction: Nonalcoholic steatohepatitis (NASH) is a leading cause of liver disease in children and adults, a major contributor to health-care expenditures, and now a leading reason for liver transplantation. Adopting lifestyle modifications with regular exercise and a focus on healthy eating habits is the primary recommendation. However, patients are often unable to achieve and sustain such changes for a variety of social, physical, psychological and genetic reasons. Thus, treatments that can prevent and reverse NASH and its associated fibrosis are a major focus of current drug development. Areas covered: This review covers the current understanding of lipotoxic liver injury in the pathogenesis of NASH and how lifestyle modification and the spectrum of drugs currently in clinical trials address the many pathways leading to the phenotype of NASH. Expert opinion: Contrary to the frequently expressed nihilistic view of our understanding of NASH and disappointment with clinical trial results, much is known about the pathogenesis of NASH and there is much reason to be optimistic that effective therapies will be identified in the next 5–10 years. Achieving this will require continued refinement of clinical trial endpoints, continued engagement of trial sponsors and regulatory authorities, and continued participation of dedicated patients in clinical trials.
Pgc1a is responsible for the sex differences in hepatic Cidec/Fsp27β mRNA expression in hepatic steatosis of mice fed a Western diet.

Hepatic fat-specific protein 27 (Cidec/Fsp27) mRNA levels have been associated with hepatic lipid droplet extent under certain circumstances. To address its hepatic expression under different dietary conditions and in both sexes, Apoe-deficient mice were subjected to different experimental conditions for 11 weeks to test the influence of cholesterol, Western diet, squalene, oleanolic acid, sex and surgical castration on Cidec/Fsp27 mRNA expression. Dietary cholesterol increased hepatic Cidec/Fsp27β expression, an effect that was suppressed when cholesterol was combined with saturated fat as represented by Western-diet feeding. Using the latter diet, oleanolic acid or squalene did not modify its expression. Females showed lower levels of hepatic Cidec/Fsp27β expression than males when they were fed Western diets, a result that was translated into lesser amount of CIDEC/FSP27 protein in lipid droplets and microsomes. This was also confirmed in Ldlr-deficient mice. Incubation with estradiol resulted in decreased Cidec/Fsp27β expression in AML12 cells. While male surgical castration did not modify the expression, ovariectomized females did show increased levels compared to control females. Females also showed increased expression of Pgc1a, suppressed by ovariectomy, and the values were significantly and inversely associated with those of Cidec/Fsp27β. When Pgc1a-deficient mice were used, the sex-differences on Cidec/Fsp27β expression disappeared. Therefore, hepatic Cidec/Fsp27β expression has a complex regulation influenced by diet and sex hormonal milieu. The mRNA sex differences are controlled by Pgc1a.
Challenges of HIV diagnosis and management in the context of pre‐exposure prophylaxis (PrEP), post‐exposure prophylaxis (PEP), test and start and acute HIV infection: a scoping review

Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV‐status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV‐specific antibody point‐of‐care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre‐exposure prophylaxis (PrEP) or post‐exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false‐negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilization of ART for immediate treatment and prevention of HIV infection.
A Spatial Adaptive Algorithm Framework for Building Pattern Recognition Using Graph Convolutional Networks

Graph learning methods, especially graph convolutional networks, have been investigated for their potential applicability in many fields of study based on topological data. Their topological data processing capabilities have proven to be powerful. However, the relationships among separate entities include not only topological adjacency, but also correlation in vision, for example, the spatial vector data of buildings. In this study, we propose a spatial adaptive algorithm framework with a data-driven design to accomplish building group division and building group pattern recognition tasks, which is not sensitive to the difference in the spatial distribution of the buildings in various geographical regions. In addition, the algorithm framework has a multi-stage design, and processes the building group data from whole to parts, since the objective is closely related to multi-object detection on topological data. By using the graph convolution method and a deep neural network (DNN), the multitask model in this study can learn human thoughts through supervised training, and the whole process only depends upon the descriptive vector data of buildings without any ancillary data for building group partition. Experiments confirmed that the method for expressing buildings and the effect of the algorithm framework proposed are satisfactory. In summary, using deep learning methods to complete the tasks of building group division and building group pattern recognition is potentially effective, and the algorithm framework is worth further research.
Connecting Air Pollution Exposure to Socioeconomic Status: A Cross-Sectional Study on Environmental Injustice among Pregnant Women in Scania, Sweden

Environmental injustice, characterized by lower socioeconomic status (SES) persons being subjected to higher air pollution concentrations, was explored among pregnant women in Scania, Sweden. Understanding if the general reduction of air pollution recorded is enjoyed by all SES groups could illuminate existing inequalities and inform policy development. “Maternal Air Pollution in Southern Sweden”, an epidemiological database, contains data for 48,777 pregnancies in Scanian hospital catchment areas and includes births from 1999–2009. SES predictors considered included education level, household disposable income, and birth country. A Gaussian dispersion model was used to model women’s average NOX and PM2.5 exposure at home residence over the pregnancy period. Total concentrations were dichotomized into emission levels below/above respective Swedish Environmental Protection Agency (EPA) Clean Air objectives. The data were analyzed using binary logistic regression. A sensitivity analysis facilitated the investigation of associations’ variation over time. Lower-SES women born outside Sweden were disproportionately exposed to higher pollutant concentrations. Odds of exposure to NOX above Swedish EPA objectives reduced over time, especially for low-SES persons. Environmental injustice exists in Scania, but it lessened with declining overall air pollution levels, implying that continued air quality improvement could help protect vulnerable populations and further reduce environmental inequalities.
Antibacterial, Antibiofilm, and Antiadhesive Properties of Different Quaternized Chitosan Derivatives

In the era of antimicrobial resistance, the identification of new antimicrobials is a research priority at the global level. In this regard, the attention towards functional antimicrobial polymers, with biomedical/pharmaceutical grade, and exerting anti-infective properties has recently grown. The aim of this study was to evaluate the antibacterial, antibiofilm, and antiadhesive properties of a number of quaternized chitosan derivatives that have displayed significant muco-adhesive properties and wound healing promotion features in previous studies. Low (QAL) and high (QAH) molecular weight quaternized chitosan derivatives were synthetized and further modified with thiol moieties or pendant cyclodextrin, and their antibacterial activity evaluated as minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC). The ability of the derivatives to prevent biofilm formation was assessed by crystal violet staining. Both QAL and QAH derivatives exerted a bactericidal and/or inhibitory activity on the growth of P. aeruginosa and S. epidermidis. The same compounds also showed marked dose-dependent anti-biofilm activity. Furthermore, the high molecular weight derivative (QAH) was used to functionalize titanium plates. The successful functionalization, demonstrated by electron microscopy, was able to partially inhibit the adhesion of S. epidermidis at 6 h of incubation. The shown ability of the chitosan derivatives tested to both inhibit bacterial growth and/or biofilm formation of clinically relevant bacterial species reveals their potential as multifunctional molecules against bacterial infections.
MiR-361-5p exerts tumor-suppressing functions in gastric carcinoma by targeting syndecan-binding protein

Supplemental Digital Content is available in the text. MiR-361-5p, a tumor-related microRNA, has been reported to be implicated in the tumorigenesis and progression of diverse types of human malignancies; however, its role in gastric carcinoma remains unclear. This study aimed to explore the biological role of miR-361-5p in gastric carcinoma and clarify the potential mechanisms involved. In the present study, miR-361-5p was found to be significantly downregulated in both gastric carcinoma tissues and cell lines. Functional studies demonstrated that enhanced expression of miR-361-5p suppressed gastric carcinoma cell proliferation in vitro, inhibited tumor growth in vivo, and induced gastric carcinoma cell apoptosis. Moreover, the tumor-suppressing effects of miR-361-5p in gastric carcinoma were abrogated by the miR-361-5p inhibitor treatment. Notably, syndecan-binding protein was downregulated by miR-361-5p via direct binding to its 3′ untranslated region in gastric carcinoma cells. Furthermore, syndecan-binding protein expression was discovered to be markedly upregulated and inversely correlated with miR-361-5p expression in gastric carcinoma tissues. Mechanistic studies revealed that restoring the expression of syndecan-binding protein alleviated miR-361-5p–induced inhibitory effects on proliferation of gastric carcinoma cells. Taken together, these findings suggest that miR-361-5p functions as a tumor suppressor in gastric carcinoma by directly targeting syndecan-binding protein and that miR-361-5p might be a novel therapeutic target for gastric carcinoma.
Insects and incest: Sib‐mating tolerance in natural populations of a parasitoid wasp

Sib‐mating avoidance is a pervasive behaviour that is expected to evolve in species subject to inbreeding depression. Although laboratory studies provide elegant demonstrations, small‐scaled bioassays minimize the costs of mate finding and choice, and thus may produce spurious findings. We therefore combined laboratory experiments with field observations to examine the existence of inbreeding avoidance using the parasitoid wasp Venturia canescens. In the laboratory, our approach consisted of mate‐choice experiments to assess kin discrimination in population cages with competitive interactions. A higher mating probability after sib rejections suggested that females could discriminate their sibs; however, in contrast to previous findings, sib‐mating avoidance was not observed. To compare our laboratory results to field data, we captured 241 individuals from two populations. Females laid eggs in the lab, and 226 daughters were obtained. All individuals were genotyped at 18 microsatellite loci, which allowed inference of the genotype of each female's mate and subsequently the relatedness within each mating pair. We found that the observed rate of sib‐mating did not differ from the probability that sibs encountered one another at random in the field, which is consistent with an absence of sib‐mating avoidance. In addition, we detected a weak but significant male‐biased dispersal, which could reduce encounters between sibs. We also found weak fitness costs associated with sib‐mating. As such, the sex‐biased dispersal that we found is probably sufficient to mitigate these costs. These results imply that kin discrimination has probably evolved for purposes other than mate choice, such as superparasitism avoidance.
Adherence is associated with a favorable outcome after lung transplantation

Non-adherence to therapy is associated with impaired outcome in solid organ allograft recipients. Outcome data are limited after lung transplantation. In a single-center cohort study, adherence was assessed in 427 patients undergoing lung transplantation from 2010 to 2013. Objective criteria of adherence were judged by health care workers on every visit on a five item Likert scale including trough level monitoring, home spirometry and contact with an overall rating of adherence between 0 and 100%. Cut-off values for good vs. suboptimal adherence were defined retrospectively. Primary outcome was allograft survival, secondary outcomes were patient survival, prevalence of chronic lung allograft dysfunction, hospitalizations, renal function and quality of life. Follow-up ended on 31st December 2018. Median adherence was 86% on 6,623 visits, this cut-off was used as a discriminator between good and suboptimal adherers. Patients with good adherence within the first three years showed better 5-year allograft (74% vs. 60%, p = 0.003) and patient survival (79% vs. 64%, p<0.001) and lower prevalence of chronic allograft dysfunction (33% vs. 45%, p = 0.011) after 5 years compared to patients with suboptimal adherence. A multidimensional adherence score proved to be a simple tool to assess adherence in clinical practice. Suboptimal adherence was associated with impaired outcome in lung transplant patients.
Presence of White Matter Lesions Associated with Diabetes-Associated Cognitive Decline in Male Rat Models of Pre-Type 2 Diabetes

Background The aim of this study was to determine the association between white matter lesions (WML) and diabetes-associated cognitive decline (DACD) in rat models of type 2 diabetes (T2DM). Material/Methods Sixty Sprague-Dawley male rats were divided into 4 groups: control, control+metformin, T2DM, and T2DM+metformin groups. The T2DM groups were fed a diet high in fat and glucose to induce impaired glucose tolerance (IGT) and then were injected with streptozotocin to induce T2DM. The Morris water maze test was used to evaluate cognitive function. Brain diffusion tensor imaging scans were performed for WML. The expression of myelin basic protein (MBP), oligodendrocyte transcription factor 1 (OLIG1), and OLIG2 (markers of brain damage and repair) was determined using immunofluorescence. After IGT, the fractional anisotropy (FA) values of the right thalamus area were significantly lower in both T2DM groups compared with controls. Results Eight weeks after streptozotocin injection, the FA values of the thalamus were lower in the T2DM (bilateral thalamus) group and T2DM+metformin (left thalamus) group than in controls, while the FA values in the left thalamus area were lower in the T2DM+metformin group than in the control and control+metformin groups. The maze escape latency was longer and the number of rats passing through the platform was smaller in the T2DM and T2DM+metformin groups than in the control group. MBP levels were lower and OLIG1 and OLIG2 levels were higher in both T2DM groups than in controls. Conclusions WML is associated with DACD and appears before the onset of T2DM and signs of DACD and plays a role in diabetes-associated cognitive decline. Metformin reduces WMLs but does not rescue cognitive dysfunction.
Mobility advice to help prevent re‐ulceration in diabetes

Clinicians and patients face a dilemma in understanding how best to resume walking after a healed diabetic neuropathic ulcer. The objectives of this brief review are to: provide context for the patient's health and mobility status; propose 5 suggestions to safely and effectively progress mobility following a healed foot ulcer; and to consider topics for future research to improve care in this area. Rates of ulcer recurrence and mortality are high, and activity is low following a diabetic foot wound. Medical and rehabilitation approaches have emphasized protection of the insensitive, fragile foot with the hope to prevent subsequent harm to the foot and person. In particular, the 1–2 months following wound unloading and “healing” have the greatest risk for ulcer recurrence. While early protection should be emphasized, a growing body of evidence suggests that over‐protection of the foot and limited walking can be harmful, presumably because of the negative effects of prolonged immobility and stress protection. Multiple recent studies report the ability of exercise and walking to have a positive effect on various diabetic foot outcomes without additional harm. Much less is known about how an ulcerated foot can resume walking after the wound is healed. This review integrates available guidelines, evidence, and precautions to suggest advice on how best to resume and progress walking in this population at high risk for ulcer recurrence.