Miracle-dz/UniFAR-FTUs huggingface dataset:
Onabotulinumtoxin A Improves Psychological Aspects in Chronic Migraine Patients

Background: Chronic migraine (CM) affects 5.4% of the Kuwaiti population. It is associated with significant headache-related disability, psychiatric comorbidity and reduced quality of life. The aim of this study is to assess the efficacy of Onabotulinumtoxin A on psychological aspects of chronic migraine patients. Methods: This prospective study over 36 months included chronic migraine patients in a tertiary headache center. Eligible patients met International Classification of Headache Disorders disorders-third edition, beta version (ICHD-III) revision criteria for chronic migraine. Patients with history of psychiatric or medical problems other than migraine disorders were excluded. Patients who received less than 4 injections cycles of Onabotulinumtoxin A were excluded. Identified patients received 155 units of Onabotulinumtoxin A quarterly according to the Phase III Research Evaluating Migraine Prophylaxis Therapy Trail (PREEMPT) protocol. Quality of life, the seven-item Generalized Anxiety Disorder (GAD-7) scores, the nine-item Patient Health Questionnaire (PHQ9), and the Pittsburgh Sleep Quality Index (PSQI) were collected before injection and at the end of the study. Mean comparison tests were performed using the independent sample t-test to assess the effects of Onabotulinumtoxin A on quality of life and comorbid symptoms of anxiety, depression, and quality of sleep. Results: The study identified 131 chronic migraine patients with a mean age of 44.92 years, mean disease duration of 12.20 years and a mean treatment sessions of 7.58. In their last visit, most of our sample showed improvement in quality of life (81%), GAD-7 (81%), PHQ9 (79%), and PSQ1 (76%). The mean score of patient satisfaction was 7.21. Onabotulinumtoxin A treatment for CM improved quality of life significantly (72.92 vs. 103.62; P < 0.0001). It was also associated with significant reduction in anxiety [GAD-7 (12.00 vs. 6.61; P < 0.0001)] and depression [PHQ-9 (17.91 vs. 12.52; P < 0.0001)] scores, as well as reduced difficulty in sleeping [PSQI (12.60 vs. 6.66; P < 0.0001)] at the last visit. Conclusion: Prophylactic Onabotulinumtoxin A treatment for CM was associated with significant improvement of quality of life, reduction in symptoms of anxiety and depression, as well as improved symptoms of poor sleep.
Evolution of phenotypic variance provides insights into the genetic basis of adaptation

Most traits are polygenic and the contributing loci can be identified by GWAS. Their adaptive architecture is, however, difficult to characterize. Here, we propose to study the adaptive architecture of traits by monitoring the evolution of their phenotypic variance during adaptation to a new environment in well-defined laboratory conditions. Extensive computer simulations show that the evolution of phenotypic variance in a replicated experimental evolution setting can distinguish between oligogenic and polygenic adaptive architectures. We compared gene expression variance in male Drosophila simulans before and after 100 generations of adaptation to a novel hot environment. The variance change in gene expression was indistinguishable for genes with and without a significant change in mean expression after 100 generations of evolution. We suggest that a majority of adaptive gene expression evolution can be explained by a polygenic architecture. We propose that tracking the evolution of phenotypic variance across generations can provide an approach to characterize the adaptive architecture. Significant Statement It is widely accepted that most complex traits have a polygenic basis. Nevertheless, it is difficult to predict which of these loci are responding to selection when a population is exposed to a new selection regime. To address this situation, we propose to infer the adaptive architecture for traits by tracking the evolution of their phenotypic variance during adaptation to a new environment. As a case study, we analyze the evolution of gene expression variance in outbred Drosophila simulans populations adapting to a new temperature regime to infer the genetic architecture of adaptive gene expression evolution. We suggested that the adaptive gene expression evolution is better explained by a polygenic architecture.
Native immunoblotting: Transfer of membrane proteins in the presence of non‐ionic detergent

For analysis with monoclonal antibodies against discontinuous epitopes and for performance of functional characterization it is important to maintain proteins native during electrophoresis and electroblotting. However, in vitro membrane proteins only remain soluble and native in the presence of non‐ionic detergent, which, on the other hand blocks the subsequent protein immobilization on nitrocellulose. With model proteins from human erythrocytes, platelets and‐serum, it has been examined if electroblotting to nitrocellulose can be performed from agarose gels in the presence of non‐ionic detergent (native blotting). Each of the following procedures were successful: (i) employment of detergents with low critical micellar concentration; e. g. Berol EMU‐043 (C 16–18, E10); (ii) insertion of a 2–3 mm thick detergent‐free agarose layer between the gel and nitrocellulose; (iii) transfer at pH 11.8 of immunoprecipitated proteins after gel wash; (iv) binding via covalent coupling to vinylsulfone activated nitrocellulose. The procedure to be chosen depends on the type of analysis and on the required binding efficiency. Compared to immunoblotting after sodium dodecyl sulfate‐gel electrophoresis, native immunoblotting was 10–30 times more sensitive. Of general applicability is the easy transfer from crossed immunoelectrophoresis gels and the possibility for performance of covalent coupling to nitrocellulose during transfer with preservation of the original binding properties of the matrix.
RIPK1 activates distinct gasdermins in macrophages and neutrophils upon pathogen blockade of innate immune signaling

Significance Pathogenic bacteria subvert host-defense mechanisms by injecting effector proteins into target cells to inhibit NF-κB and MAPK signaling. Detection of such effector proteins, such as YopJ from pathogenic Yersinia, activates RIPK1 and caspase-8–dependent cell death that promotes antibacterial defense. While recent studies demonstrate that caspase-8 cleaves the pore-forming protein gasdermin D to promote anti-Yersinia defense, whether RIPK1 activates other substrates is unclear. Here, we demonstrate that RIPK1 activates gasdermin D in macrophages and the related gasdermin E in neutrophils to promote host defense. Neutralization of IL-1β in vivo promoted host susceptibility to Yersinia infection in wild-type, but not Gsdme−/−, animals, revealing an unexpected role for gasdermin E in IL-1β secretion during bacterial infection. Injection of effector proteins to block host innate immune signaling is a common strategy used by many pathogenic organisms to establish an infection. For example, pathogenic Yersinia species inject the acetyltransferase YopJ into target cells to inhibit NF-κB and MAPK signaling. To counteract this, detection of YopJ activity in myeloid cells promotes the assembly of a RIPK1–caspase-8 death–inducing platform that confers antibacterial defense. While recent studies revealed that caspase-8 cleaves the pore-forming protein gasdermin D to trigger pyroptosis in macrophages, whether RIPK1 activates additional substrates downstream of caspase-8 to promote host defense is unclear. Here, we report that the related gasdermin family member gasdermin E (GSDME) is activated upon detection of YopJ activity in a RIPK1 kinase–dependent manner. Specifically, GSDME promotes neutrophil pyroptosis and IL-1β release, which is critical for anti-Yersinia defense. During in vivo infection, IL-1β neutralization increases bacterial burden in wild-type but not Gsdme-deficient mice. Thus, our study establishes GSDME as an important mediator that counteracts pathogen blockade of innate immune signaling.
Simulation of protozoa-induced mineralization of bacterial carbon and nitrogen

Modelling in soil ecological research is a means of linking the dynamics of microbial and faunal populations to soil processes. The objectives of this study were (i) to simulate bacterial-protozoan interactions and flows of C and N in clay loam Orthic Black Chernozemic soil under laboratory condtions; and (ii) to quantify the flux of C and N (inputs and outputs) through various pools using the simulation model. The unique features of this model are: (i) it combines the food chain with specific soil C and N pools, and (ii) it simultaneously traces the flows of C, 14C, N and 15N. It was possible to produce a model that fitted the data observed for the soil. The simulated CO2-C evolved during the first 12 d was due mainly to glucose addition (171 μg C g−1 soil) and cycling of C in the soil (160 μg C g−1 soil). During this interval, bacterial C uptake was 5.5-fold greater than the initial bacterial C pool size. In the first 12 d protozoa directly increased total CO2-C evolution by 11% and increased NH4-N mine.
Prioritization and Evaluation of Flooding Tolerance Genes in Soybean [Glycine max (L.) Merr.]

Soybean [Glycine max (L.) Merr. ] is one of the most important legume crops abundant in edible protein and oil in the world. In recent years there has been increasingly more drastic weather caused by climate change, with flooding, drought, and unevenly distributed rainfall gradually increasing in terms of the frequency and intensity worldwide. Severe flooding has caused extensive losses to soybean production and there is an urgent need to breed strong soybean seeds with high flooding tolerance. The present study demonstrates bioinformatics big data mining and integration, meta-analysis, gene mapping, gene prioritization, and systems biology for identifying prioritized genes of flooding tolerance in soybean. A total of 83 flooding tolerance genes (FTgenes), according to the appropriate cut-off point, were prioritized from 36,705 test genes collected from multidimensional genomic features linking to soybean flooding tolerance. Several validation results using independent samples from SoyNet, genome-wide association study, SoyBase, GO database, and transcriptome databases all exhibited excellent agreement, suggesting these 83 FTgenes were significantly superior to others. These results provide valuable information and contribution to research on the varieties selection of soybean.
Acylated Ghrelin is Protective Against 6-OHDA-induced Neurotoxicity by Regulating Autophagic Flux

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, and our previous study revealed that autophagic flux dysfunction contributes to the neuron death in 6-OHDA-induced PD models. Acylated ghrelin is a neuropeptide that has a variety of actions in the central nervous system. In the current study, we aimed to investigate whether ghrelin is neuroprotective in 6-OHDA-induced rat model and SH-SY5Y cell model and whether it is related to autophagic flux regulation. We observed that ghrelin could effectively reduce apomorphine-induced contralateral rotation in 6-OHDA-induced PD rats, preserve the expression of tyrosine hydroxylase (TH) and increase the cell viability. It could upregulate the expression of autophagy related proteins like Atg7 and LC3-II and downregulate p62, and downregulate apoptosis related proteins like bax and cleaved caspase 3. SH-SY5Y cells transfected with adenovirus Ad-mCherry-GFP-LC3B further revealed that ghrelin could relieve the autophagic flux dysfunction induced by 6-OHDA. Lysotracker staining showed that ghrelin could reverse the decrease in lysosomes induced by 6-OHDA and immunofluorescence staining revealed a reverse of TFEB level in SH-SY5Y cells. Blocking autophagy activation with 3-methyladenine (3-MA) in rats treated with ghrelin and 6-OHDA showed no notable change in apoptosis-related markers, while blocking autophagosome fusion with lysosomes with chloroquine could notably reverse the downregulation of bax/bcl-2 ratio and cleaved caspase three expression by ghrelin. Additionally, knockdown ATG7, the upstream regulator of autophagy, with siRNA could further decrease the number of apoptotic cells in SH-SY5Y cells exposed to 6-OHDA and treated with ghrelin, while knockdown TFEB, a key transcription factor for lysosome biosynthesis and function, with siRNA could completely abolish the anti-apoptosis effect of ghrelin. These data suggest that ghrelin is neuroprotective in 6-OHDA-induced PD models via improving autophagic flux dysfunction and restoration of TFEB level.
Gas-dynamic acceleration of laser-ablation plumes: Hyperthermal particle energies under thermal vaporization

The expansion of a plume produced by low-fluence laser ablation of graphite in vacuum is investigated experimentally and by direct Monte Carlo simulations in an attempt to explain hyperthermal particle energies for thermally vaporized materials. We demonstrate that the translation energy of neutral particles, ∼2 times higher than classical expectations, is due to two effects, hydrodynamic plume acceleration into the forward direction and kinetic selection of fast particles in the on-axis region. Both effects depend on the collision number within the plume and on the particles internal degrees of freedom. The simulations allow ablation properties to be evaluated, such as ablation rate and surface temperature, based on time-of-flight measurements. Available experimental data on kinetic energies of various laser-produced particles are well described by the presented model.
Simultaneous Control of Infection and Inflammation by Keratin-Derived Antibacterial Peptides (KAMPs) Targeting TLRs and Co-Receptors

The use and the timing of initiation of steroids for controlling unwanted infectious inflammation are major clinical dilemmas due to their possible adverse effects including delayed microbial clearance and wound healing. Compounding this difficulty is the continued emergence of drug-resistant bacteria; yet anti-infective strategies aiming at augmenting inflammatory responses to facilitate bacterial killing cannot be used to treat infections involving vulnerable tissues. As is the case with bacterial keratitis, excessive inflammation jeopardizes corneal transparency leading to devastating vision loss. Hence, a two-pronged remedy possessing both anti-infective and anti-inflammatory properties would be helpful for tackling antibiotic resistance and enabling prompt inflammation control at once. Using murine primary neutrophils, macrophages and sterile corneal inflammation models, we found that non-toxic and pro-healing human keratin 6a-derived antimicrobial peptides (KAMPs) with a native 10-or 18-amino-acid sequence suppress LTA- and LPS-induced NF-кB and IRF3 activation, proinflammatory cytokine production, as well as phagocyte recruitment, independently of their bactericidal function. Mechanistically, direct binding of KAMPs to cell surface TLR2 and TLR co-receptors CD14 and MD-2 not only blocks their bacterial ligand docking sites, but also reduces cell surface availability of TLR2 and TLR4 through promotion of receptor endocytosis. Benefitting from the dual functions of topical KAMPs, experimental bacterial keratitis caused was effectively prevented or controlled, as evidenced by significant reductions of corneal opacification and inflammatory cell infiltration in addition to enhanced bacterial clearance. These findings reveal multiple TLR-targeting activities of KAMPs and demonstrate their therapeutic potential as a multifunctional drug for managing sterile and infectious inflammatory diseases. One Sentence Summary Bifunctional native keratin peptides allow concurrent alleviation of inflammation and infection to avoid functional damages in vulnerable tissues.
COVID-19 Disease Course in Former Smokers, Smokers and COPD Patients

The severe respiratory and systemic disease named coronavirus disease-2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the COVID-19 pandemic presents a huge social and health challenge worldwide. Many different risk factors are associated with disease severity, such as systemic arterial hypertension, diabetes mellitus, obesity, older age, and other co-infections. Other respiratory diseases such as chronic obstructive pulmonary disease (COPD) and smoking are common comorbidities worldwide. Previous investigations have identified among COVID-19 patients smokers and COPD patients, but recent investigations have questioned the higher risk among these populations. Nevertheless, previous reports failed to isolate smokers and COPD patients without other comorbidities. We performed a longitudinal evaluation of the disease course of smokers, former smokers, and COPD patients with COVID-19 without other comorbidities, from hospitalization to hospital discharge. Although no difference between groups was observed during hospital admission, smokers and COPD patients presented an increase in COVID-19-associated inflammatory markers during the disease course in comparison to non-smokers and former smokers. Our results demonstrated that smoking and COPD are risk factors for severe COVID-19 with possible implications for the ongoing pandemic.
Trastuzumab Provides a Comparable Prognosis in Patients With HER2-Positive Breast Cancer to Those With HER2-Negative Breast Cancer: Post Hoc Analyses of a Randomized Controlled Trial of Post-Mastectomy Hypofractionated Radiotherapy

Background and Purpose We investigated the locoregional effect of trastuzumab, and determined whether patients with human epidermal growth factor receptor (HER)2-positive breast cancer (BC) treated with trastuzumab could achieve comparable efficacy to that of patients with HER2-negative BC. Materials and Methods This was post hoc analyses of data of 793 BC patients from a randomized controlled trial comparing post-mastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy. Survival rates were analyzed by the Kaplan–Meier method and compared by the log-rank test. Results Patients were classified into three groups: HER2-negative (HER2−; n = 547), HER2-positve with trastuzumab (HER2+ + T; n = 136), and HER2-positive without trastuzumab (HER2+ − T; n = 110). The HER2+ + T group had significantly lower locoregional recurrence (LRR, 6.0% vs. 13.9%), distant metastasis (DM, 17.4% vs. 33.8%) and higher disease-free survival (DFS, 81.2% vs. 61.9%) at 5 years than that of the HER2+ − T group (P <.05). The HER2− group had significantly lower LRR (6.8% vs. 13.9%), DM (22.4% vs. 33.8%) and higher DFS (76.1% vs. 61.9%) at 5 years than that of the HER2+ − T group (P <.05). The difference in LRR, DM and DFS at 5 years was not significant between the HER2+ + T group and HER2− group (P >.05). Different annual LRR patterns was found among groups according to HR status. Conclusion Trastuzumab reduces LRR in patients with locally advanced HER2-positive BC who have received post-mastectomy radiotherapy. It provides comparable DFS to that with patients with HER2-negative BC.
A study of Mutation in ATP7B gene and its correlation with clinical phenotype and radiological features in Wilson Disease patients

Introduction Wilson Disease (WD) is an autosomal recessive disease caused by mutations in the ATP7B gene. Clinical manifestations of WD are variable. Identification of prevalent mutations in a given population is necessary to provide mutation-based molecular diagnosis. Previous studies have detected common mutations in this part of the world and our study aimed to correlate genotype with clinical and radiological features. Methods A descriptive cross-sectional observational study was conducted over a period of two years in a tertiary care hospital and neurology referral unit of Kolkata, India. All WD patients within the study period and meeting the inclusion criteria were included. Demographic data collection, clinical examination and relevant laboratory investigations were done. Magnetic resonance imaging of brain and cognitive assessment by Mini Mental Score Exam (MMSE) were also performed. Blood was collected for genetic analyses. PCR-Sanger sequencing of exons 2,4,6,8,10,14,16,18 of ATP7B gene was done based on previous reports of mutation hotspots of ATP7B gene for WD in Eastern India. Genotype phenotype correlation was attempted using two supervised machine learning methods, viz. logistic regression with an elastic-net penalty and the random forest. Results Of 52 WD patients were included in the study, 57.7% were males. The mean age at diagnosis was 13.96 years. Majority (61.8%) of the patients had dystonia on presentation, followed by dysarthria (41.2%), tremor (17.6%) and ataxia (11.8%). The mean MMSE and Frontal Assessment Battery score were 23.74 and 10.63 respectively and both were lower than the normal baseline values.Out of the total cohort of 52 patients,15(28.8%) harbored previously reported common mutations from this part of the country. Of the 15, 12 had the same mutation of c.813C>A(p.cys271Ter). The presence of common mutationswas associated with several distinct clinical phenotypes in the mathematical models but larger sample sizes are needed to corroborate the correlation. Conclusions WD patients in eastern India have significant genotypic and phenotypic diversity. Further studies with larger samples and screening of remaining exons are warranted.
Use Of Canine Olfactory Detection For COVID-19 Testing Study On U.A.E. Trained Detection Dog Sensitivity

This study aimed to evaluate the sensitivity of 21 dogs belonging to different United Arab Emirates (UAE) Ministry of Interior (MOI), trained for COVID-19 olfactory detection. The study involved 17 explosives detection dogs, two cadaver detection dogs and two dogs with no previous detection training. Training lasted two weeks before starting the validation protocol. Sequential five and seven-cone line-ups were used with axillary sweat samples from symptomatic COVID-19 individuals (SARS-CoV-2 PCR positive) and from asymptomatic COVID-19 negative individuals (SARS-CoV-2 PCR negative). A total of 1368 trials were performed during validation, including 151 positive and 110 negative samples. Each line-up had one positive sample and at least one negative sample. The dog had to mark the positive sample, randomly positioned behind one of the cones. The dog, handler and data recorder were blinded to the positive sample location. The calculated overall sensitivities were between 71% and 79% for three dogs, between83% and 87% for three other dogs, and equal to or higher than 90% for the remaining 15 dogs (more than two thirds of the 21 dogs). After calculating the overall sensitivity for each dog using all line-ups, “matched” sensitivities were calculated only including line-ups containing COVID-19 positive and negative samples strictly comparable on confounding factors such as diabetes, anosmia, asthma, fever, body pain, diarrhoea, sex, hospital, method of sweat collection and sampling duration. Most of the time, the sensitivities increased after matching. Pandemic conditions in the U.A. E. , associated with the desire to use dogs as an efficient mass-pretesting tool has already led to the operational deployment of the study dogs. Future studies will focus on comparatives fields-test results including the impact of the main COVID-19 comorbidities and other respiratory tract infections.