Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased Levels of Coagulation Factor XI in Plasma Are Related to Alzheimer's Disease Diagnosis.

BACKGROUND Alzheimer's disease is a complex disorder of unclear etiology that develops in the elderly population. It is a debilitating, progressive neurodegeneration for which disease-modifying therapies do not exist. Previous studies have suggested that, for a subset of patients, dysregulation in hemostasis might be one of the molecular mechanisms that ultimately leads to the development of neurodegeneration resulting in cognitive decline that represents the most prominent symptomatic characteristic of Alzheimer's disease. OBJECTIVE To examine a relationship between factors that are part of coagulation and anticoagulation pathways with cognitive decline that develops during Alzheimer's disease. METHODS SOMAscan assay was used to measure levels of coagulation/anticoagulation factors V, VII, IX, X, Xa, XI, antithrombin III, protein S, protein C, and activated protein C in plasma samples obtained from three groups of subjects: 1) subjects with stable cognitively healthy function, 2) subjects with stable mild cognitive impairment, and 3) subjects diagnosed with probable Alzheimer's disease. RESULTS Our results show that protein levels of coagulation factor XI are significantly increased in patients who are diagnosed with probable Alzheimer's disease compared with cognitively healthy subjects or patients diagnosed with mild cognitive impairment. Furthermore, our results demonstrate that significant predictors of Alzheimer's-type diagnosis are factors IX and XI-an increase in both factors is associated with a reduction in cognitive function. CONCLUSION Our study justifies further investigations of biological pathways involving coagulation/anticoagulation factors in relation to dementia, including dementia resulting from Alzheimer's-type neurodegeneration.
Ultrasound evaluation of postsurgical shoulder after rotator cuff repair: comparison of clinical results

Background The relationship between the imaging parameters on postoperative ultrasound (US) other than repaired tendon integrity with clinical outcome such as postoperative residual pain has not been well defined. Purpose To investigate whether the repaired tendon thickness and subdeltoid fluid collection after rotator cuff repair are correlated with early postoperative clinical outcome. Material and Methods This retrospective study included 54 patients who underwent repair of the arthroscopic rotator cuff either by suture-bridge or single-row technique and postoperative US. We assessed the relationship between the sonographic parameters, including repaired supraspinatus tendon thickness and subdeltoid fluid collection, with the clinical outcome represented by the Korean Shoulder Scoring system (KSS) score using correlation coefficients (R). Also, the subgroup analysis was done to assess the differences by surgical technique and patients’ age. Results There was a significant inverse relationship between the amount of subdeltoid fluid collection and degree of self-assessed pain improvement of the patients (P < 0.05), although every KSS category showed statistically insignificant tendency of inverse relationship with the fluid thickness. However, there was no statistically significant relationship between the thickness of repaired supraspinatus tendon and KSS scores. In patients aged >60 years, a statistically significant inverse relationship between thickness of subdeltoid fluid collection and difference value of the KSS scores in category of function was observed with both interpreters (P = 0.015 and P = 0.04, respectively). Conclusion Subdeltoid fluid collection measured on US after repair of the arthroscopic rotator cuff in the early postoperative period has significant association with the patients’ subjective clinical outcome.
The Trajectory of Caregiver Burden and Risk Factors in Dementia Progression: A Systematic Review

Background: Caring for patients with dementia at home is often a long-term process, in which the independence of the patient declines, and more responsibility and supervision time is required from the informal caregiver. Objective: In order to minimize and reduce caregiver burden, it is important to explore its trajectory and the accompanying risk factors as dementia progresses; the objective of this systematic review. Methods: PRISMA guidelines were followed in this systematic review. Three databases, PubMed, PsycINFO, and EMbase, were systematically searched in November 2019 using specific keywords. Results: 1,506 hits emerged during the systematic search but only eleven articles actually met the inclusion criteria for this review. The trajectory of caregiver burden is highly variable and depends on multiple factors. Important risk factors included: patients’ behavioral and neuropsychiatric symptoms, and their decline in functioning in (I)ADL; the caregiver’s age, gender, and physical and mental health; and, within the dyads (patient/caregiver), cohabitation and kinship. Conclusion: There is no one-size-fits-all for predicting how caregiver burden will change over time, but specific factors (like being a spouse and increased behavioral impairment and decline in functional status in the patient) may heighten the risk. Other factors, not yet comprehensively included in the published studies, might also prove to be important risk factors. Future research in the field of reducing caregiver burden is recommended to integrate the patient, caregiver, and context characteristics in the trajectory of caregiver burden, and to assess more clearly the phase of the dementia progression and use of external resources.
Rethinking bedtime resistance in children with autism: is restless legs syndrome to blame?

STUDY OBJECTIVES In this study we investigated the clinical correlates of restless legs syndrome in children with autism and report on our experiences with response to treatment. METHODS A retrospective chart review of children seen in our sleep center from 2016-2019 was performed to identify children with autism and chronic insomnia. Patients underwent clinical assessments for restless legs symptomatology. Overnight polysomnogram, serum ferritin testing, and response to clinical treatment data were collected. RESULTS A total of 103 children with autism and chronic insomnia were identified (age range 2 - 19 years). Of these, 41 children (39%) were diagnosed with restless legs syndrome. The diagnosis of restless legs syndrome was associated with significantly lower serum ferritin levels (mean 29 ±18.62 ng/mL versus non-RLS 56.7 ± 17.59, P<0.001) and higher PLMS on PSG (8.12 ± 6.6 versus non-RLS 0.06 ±0.17). The presence of leg kicking, body rocking, or any symptoms involving the legs, highly correlated with the diagnosis of RLS. Positive treatment response was noted in nearly all treated patients, including those treated with oral iron supplementation alone (25 children, 23 responders), gabapentin alone (12 children, all responders), and combination therapy (3 children, all responders). CONCLUSIONS Our findings suggest restless legs syndrome may represent an underrecognized cause of insomnia in children with autism. Initial assessment should include a thorough query of behaviors related to nocturnal motor complaints, because restless legs syndrome may be a treatable cause of sleep disruption.
Are Parental Alcohol Use Disorder Histories Associated With Offspring Behavior Problems at Age 2?

OBJECTIVE Studies of clinical and high-risk samples have demonstrated associations between parental alcohol use disorders (AUDs) and offspring's internalizing and externalizing behavior problems during adolescence and early adulthood. It remains unclear, however, whether associations between parental AUD histories and offspring behavior problems are evident among very young offspring who were not directly exposed to a parent who experienced an active AUD episode during the child's lifetime. The present study sought to evaluate internalizing and externalizing behavior problems among young children as a function of paternal and maternal AUD histories and associated clinical features. METHOD The community sample consisted of 160 families with a 2-year-old child and parents who did not experience an AUD episode since the child was born. Parental AUD histories and associated clinical features were evaluated with semistructured interviews, and parental reports of child internalizing and externalizing behaviors were assessed with an age-appropriate behavior checklist. RESULTS In contrast to previous findings from clinical and high-risk samples, when paternal and maternal AUD histories and associated clinical features were evaluated as predictors of child behavior problems, no statistically significant associations were detected (βs ranged from .01 to .18). Moderating effects of sex of the offspring were also not significant. CONCLUSIONS Parental AUD histories do not appear to confer risk for offspring internalizing or externalizing behavior problems at age 2. The emergence of such behavior problems may be limited to specific developmental periods during childhood or reflect the impact of direct exposure to parents with alcohol-related problems.
EphA4 Is Required for Neural Circuits Controlling Skilled Reaching

Skilled forelimb movements are initiated by feedforward motor commands conveyed by supraspinal motor pathways. The accuracy of reaching and grasping relies on internal feedback pathways that update ongoing motor commands. In mice lacking the axon guidance molecule EphA4, axonal misrouting of the corticospinal tract and spinal interneurons is manifested, leading to a hopping gait in hindlimbs. Moreover, mice with a conditional forebrain deletion of EphA4, display forelimb hopping in adaptive locomotion and exploratory reaching movements. However, it remains unclear how loss of EphA4 signaling disrupts function of forelimb motor circuit and skilled reaching and grasping movements. Here we investigated how neural circuits controlling skilled reaching were affected by the loss of EphA4. Both male and female C57BL/6 wild-type, heterozygous EphA4+/−, and homozygous EphA4−/− mice were used in behavioral and in vivo electrophysiological investigations. We found that EphA4 knock-out (−/−) mice displayed impaired goal-directed reaching movements. In vivo intracellular recordings from forelimb motor neurons demonstrated increased corticoreticulospinal excitation, decreased direct reticulospinal excitation, and reduced direct propriospinal excitation in EphA4 knock-out mice. Cerebellar surface recordings showed a functional perturbation of the lateral reticular nucleus–cerebellum internal feedback pathway in EphA4 knock-out mice. Together, our findings provide in vivo evidence at the circuit level that loss of EphA4 disrupts the function of both feedforward and feedback motor pathways, resulting in deficits in skilled reaching. SIGNIFICANCE STATEMENT The central advances of this study are the demonstration that null mutation in the axon guidance molecule EphA4 gene impairs the ability of mice to perform skilled reaching, and identification of how these behavioral deficits correlates with discrete neurophysiological changes in central motor pathways involved in the control of reaching. Our findings provide in vivo evidence at the circuit level that loss of EphA4 disrupts both feedforward and feedback motor pathways, resulting in deficits in skilled reaching. This analysis of motor circuit function may help to understand the pathophysiological mechanisms underlying movement disorders in humans.
Safety of pembrolizumab for resected stage III melanoma

ABSTRACT Introduction Patients with resected stage III melanoma have a heterogeneous prognosis with an especially high risk of relapse for patients with stage IIIB, IIIC and IIID according to the 2018 classification in AJCC Cancer Staging Manual, 8th edition (AJCC-8). Ipilimumab was the first immune checkpoint inhibitor (ICI) to show prolonged overall survival (OS) but at the cost of high toxicity. Pembrolizumab and nivolumab are inhibitors of programmed cell death 1 (PD-1) and showed prolonged relapse-free survival (RFS) in patients with resected stage III melanoma at high risk of relapse compared to placebo and ipilimumab, respectively. Areas covered The aim of this article is to review the mechanisms of action, pharmacokinetics and safety data of pembrolizumab in resected stage III melanoma and to compare its safety profile to other immune checkpoint inhibitors for the same indication. Expert opinion Pembrolizumab as adjuvant therapy of resected stage III melanoma showed an acceptable safety profile, which is comparable to that in advanced melanoma. However, it caused one death. There is uncertainty about its benefits in AJCC-8 stage IIIA melanoma patients. Additionally, caution is required since OS and long-term safety data are not available yet.
Analysis and Comparison of Nutritional Composition for Dried Maca

Objective To evaluate nutritional value of Maca (Lepidium meyenii Walp), a tuber of Andine origin cultivated in Peru by comparison with Chinese traditional corps.Method Using national standards or AOAC methods, content of protein/amino-acid, lipid/fatty acid, carbohydrate, 11 kinds of minerals and 12 kinds of vitamins in dried Maca were analyzed, and compared with that in potato, sweet potato, carrot, wheat flour and rice.Results It was showed that Maca was rich in protein, minerals and vitamins, with higher value than potato and sweet potato after adjusting water content.Conclusion It was suggested that Maca may be a potential tuber source for introduction and development because of its nutritional value.
Examining the Association of Knee Pain With Modifiable Cardiometabolic Risk Factors

A well‐established link exists between obesity and knee osteoarthritis, and recent research has implicated diabetes mellitus as a potential cause of cartilage degeneration. The objective of this study was to use the National Health and Nutrition Examination Survey (NHANES) database to examine the association between knee pain and various metabolic factors.
Coupled transmembrane mechanisms control MCU-mediated mitochondrial Ca2+ uptake

Significance Control of the level of calcium inside mitochondria is important because mitochondrial calcium regulates metabolism, cell death, and cellular signaling. The main pathway for mitochondrial calcium uptake is a calcium-selective ion channel complex in the inner mitochondrial membrane called the mitochondrial calcium uniporter (MCU). How the activity of the MCU ion channel is regulated is controversial. Here we employed electrophysiology of single isolated mitochondria to record MCU calcium and sodium ionic currents. We found that MCU ion channel activity is controlled by distinct Ca2+-regulated mechanisms on both sides of the inner mitochondrial membrane that are coupled to each other. These mechanisms allow for enhanced cellular regulation of mitochondrial calcium homeostasis. Ca2+ uptake by mitochondria regulates bioenergetics, apoptosis, and Ca2+ signaling. The primary pathway for mitochondrial Ca2+ uptake is the mitochondrial calcium uniporter (MCU), a Ca2+-selective ion channel in the inner mitochondrial membrane. MCU-mediated Ca2+ uptake is driven by the sizable inner-membrane potential generated by the electron-transport chain. Despite the large thermodynamic driving force, mitochondrial Ca2+ uptake is tightly regulated to maintain low matrix [Ca2+] and prevent opening of the permeability transition pore and cell death, while meeting dynamic cellular energy demands. How this is accomplished is controversial. Here we define a regulatory mechanism of MCU-channel activity in which cytoplasmic Ca2+ regulation of intermembrane space-localized MICU1/2 is controlled by Ca2+-regulatory mechanisms localized across the membrane in the mitochondrial matrix. Ca2+ that permeates through the channel pore regulates Ca2+ affinities of coupled inhibitory and activating sensors in the matrix. Ca2+ binding to the inhibitory sensor within the MCU amino terminus closes the channel despite Ca2+ binding to MICU1/2. Conversely, disruption of the interaction of MICU1/2 with the MCU complex disables matrix Ca2+ regulation of channel activity. Our results demonstrate how Ca2+ influx into mitochondria is tuned by coupled Ca2+-regulatory mechanisms on both sides of the inner mitochondrial membrane.
Preconditioning human pharyngeal motor cortex enhances directional metaplasticity induced by repetitive transcranial magnetic stimulation

Recent studies have proposed therapeutic potential for repetitive transcranial magnetic stimulation (rTMS) in swallowing rehabilitation, yet its outcomes vary across individuals and studies. Such variability may be related to the brain state before stimulation. Metaplasticity is a higher order plasticity which regulates cortical response to plasticity changes. Studies have shown that preconditioning of the hand motor cortex could increase cortical capacity for neuroplastic change and enhance rTMS outcomes. We investigated, for the first time, the directional metaplastic properties in human pharyngeal motor cortex using preconditioned rTMS. We found that preconditioned rTMS with specific time intervals between preconditioning and conditioning rTMS had stronger stimulation effects in both swallowing neurophysiology and behaviour than that without preconditioning. Our results provide evidence for enhanced directional metaplasticity in pharyngeal motor cortex and new insights into its clinical application for dysphagia.
Occupational respiratory morbidity among hair and beauty salon workers in Udupi taluk, Karnataka, India.

BACKGROUND The Indian hair and beauty salon industry is growing rapidly due to the demand for beauty and personal care services and products. Workers in the industry are vulnerable to several occupational factors such as chemicals, confined space, and poor ventilation. Chemicals in the products used are known or suspected to cause allergies, respiratory, neurological and reproductive health problems and cancer. METHODS The present study was carried out to determine the factors associated with the occurrence of respiratory morbidity among hair and beauty salon workers of Udupi taluk, Karnataka, India. A total of 240 salon workers were recruited for the study. A semistructured, interviewer-led questionnaire was used to collect data. Peak expiratory flow rate (PEFR) was done using a JSB peak flow meter. RESULTS The frequency of respiratory morbidity among participating beauty salon workers was 19%. Men reported respiratory symptoms more frequently than women. Receiving training on work materials and practices was a significant protective factor (odds ratio = 0.3; 95% confidence interval: 0.1-0.7) for the occurrence of respiratory morbidity. The mean observed PEFR in these workers was significantly lower than their predicted values. While 61.2% of the workers were using some form of personal protective equipment, only 4% of workers used a mask or respiratory protection. CONCLUSION Hair and beauty salon workers are at risk of developing respiratory morbidity potentially from harmful exposures and lack of effective control measures at the workplace.
In-silico approach to the development of a prototype clinical information system for pediatric units

There is an observed serious challenge to the provision and management of pediatric healthcare and facilities in most African countries. This has probably contributed to the high mortality rates recorded among African children. It is thus imperative to evaluate all possible approaches to the development of the appropriate manage of the problem. In-silico approaches to information management of pediatrics sections of hospitals could for example help reduce mortality rates among children. This study was aimed at developing a prototype clinic information system for keeping track of infants’ clinical records, diagnosis of their various ailments, proffering possible solutions and their respective responses to drug treatments. Research focus was on the pediatric sections of some hospitals located in southwestern part of Nigeria, particularly sections in care of the children between the ages of 5 and 9 years. A monthly or annual report generated from this system will assist in making proper recommendation to research institutions on ways of improving chemotherapeutic management of common diseases of infants and to governmental agencies on the need for more funding to support in this quest. C#. Net was the programming language used for the implementation of the system, while SQL server 2008 was used to provide the database support. It is hoped that the developed system will help in the reduction of infant mortality rates in hospitals were it is implemented.
Fabrication of a Robust PEM Water Electrolyzer Based on Non-Noble Metal Cathode Catalyst: [Mo3 S13 ]2- Clusters Anchored to N-Doped Carbon Nanotubes.

High investment costs and a dependence on noble metal catalysts currently obstruct the large-scale implementation of proton exchange membrane water electrolyzers (PEMWEs) for converting fluctuating green electricity into chemical energy via water splitting. In this context, this work presents a high-performing and stable non-noble metal catalyst for the hydrogen evolution reaction (HER), consisting of [Mo3 S13 ]2- clusters supported on nitrogen doped carbon nanotubes (NCNTs). Strikingly, a significant electrochemically induced activation of the Mo3 S13 -NCNT catalyst at high current densities is observed in full cell configuration, enabling a remarkable current density of 4 A cm-2 at a cell voltage of 2.36 V. To the authors' knowledge, this is the highest reported value to date for a PEMWE full cell using a non-noble metal HER catalyst. Furthermore, only a minor degradation of 83 µV h-1 is observed during a stability test of 100 h constant current at 1 A cm-2 , with a nearly unchanged polarization behavior after the current hold. Catalyst stability and activity are additionally analyzed via online dissolution measurements. X-ray photoelectron spectroscopy examination of the catalyst before and after electrochemical application reveals a correlation between the electrochemical activation occurring via electrodissolution with changes in the molecular structure of the Mo3 S13 -NCNT catalyst.
Covariate‐driven factorization by thresholding for multiblock data

Multiblock data, where multiple groups of variables from different sources are observed for a common set of subjects, are routinely collected in many areas of science. Methods for joint factorization of such multiblock data are being developed to explore the potentially joint variation structure of the data. While most of the existing work focuses on delineating joint components, shared across all data blocks, from individual components, which is only relevant to a single data block, we propose to model and estimate partially joint components across some, but not all, data blocks. If covariates, with potential multiblock structures, are available, then the components are further modeled to be driven by the covariate information. To estimate such a covariate‐driven, block‐structured factor model, we propose an iterative algorithm based on thresholding, by transforming the problem of signal segmentation into a grouped variable selection problem. The proposed factorization provides accurate estimation of individual and (partially) joint structures in multiblock data, as confirmed by simulation studies. In the analysis of a real multiblock genomic dataset from the Cancer Genome Atlas project, we demonstrate that the estimated block structures provide straightforward interpretation and facilitate subsequent analyses.