Miracle-dz/UniFAR-FTUs huggingface dataset:
Age‐related nitration/dysfunction of myogenic stem cell activator HGF

Abstract Mechanical perturbation triggers activation of resident myogenic stem cells to enter the cell cycle through a cascade of events including hepatocyte growth factor (HGF) release from its extracellular tethering and the subsequent presentation to signaling‐receptor c‐met. Here, we show that with aging, extracellular HGF undergoes tyrosine‐residue (Y) nitration and loses c‐met binding, thereby disturbing muscle homeostasis. Biochemical studies demonstrated that nitration/dysfunction is specific to HGF among other major growth factors and is characterized by its locations at Y198 and Y250 in c‐met‐binding domains. Direct‐immunofluorescence microscopy of lower hind limb muscles from three age groups of rat, provided direct in vivo evidence for age‐related increases in nitration of ECM‐bound HGF, preferentially stained for anti‐nitrated Y198 and Y250‐HGF mAbs (raised in‐house) in fast IIa and IIx myofibers. Overall, findings highlight inhibitory impacts of HGF nitration on myogenic stem cell dynamics, pioneering a cogent discussion for better understanding age‐related muscle atrophy and impaired regeneration with fibrosis (including sarcopenia and frailty).
Voltage gated sodium and calcium channels: Discovery, structure, function, and Pharmacology

ABSTRACT Voltage-gated sodium channels initiate action potentials in nerve and muscle, and voltage-gated calcium channels couple depolarization of the plasma membrane to intracellular events such as secretion, contraction, synaptic transmission, and gene expression. In this Review and Perspective article, I summarize early work that led to identification, purification, functional reconstitution, and determination of the amino acid sequence of the protein subunits of sodium and calcium channels and showed that their pore-forming subunits are closely related. Decades of study by antibody mapping, site-directed mutagenesis, and electrophysiological recording led to detailed two-dimensional structure-function maps of the amino acid residues involved in voltage-dependent activation and inactivation, ion permeation and selectivity, and pharmacological modulation. Most recently, high-resolution three-dimensional structure determination by X-ray crystallography and cryogenic electron microscopy has revealed the structural basis for sodium and calcium channel function and pharmacological modulation at the atomic level. These studies now define the chemical basis for electrical signaling and provide templates for future development of new therapeutic agents for a range of neurological and cardiovascular diseases.
Conserved antigen structures and antibody-driven variations on foot-and-mouth disease virus serotype A revealed by bovine neutralizing monoclonal antibodies

Foot-and-mouth disease virus (FMDV) serotype A is antigenically most variable within serotypes. The structures of conserved and variable antigenic sites were not well resolved. Here, a historical A/AF72 strain from A22 lineage and a latest A/GDMM/2013 strain from G2 genotype of Sea97 lineage were respectively used as bait antigen to screen single B cell antibodies from bovine sequentially vaccinated with A/WH/CHA/09 (G1 genotype of Sea97 lineage), A/GDMM/2013 and A/AF72 antigens. Total of 39 strain-specific and 5 broad neutralizing antibodies (bnAbs) were isolated and characterized. Two conserved antigenic sites were revealed by the Cryo-EM structures of FMDV serotype A with two bnAbs W2 and W125. The contact sites with both VH and VL of W125 were closely around icosahedral threefold axis and covered the B-C, E-F, and H-I loops on VP2 and the B-B knob and H-I loop on VP3; while contact sites with only VH of W2 concentrated on B-B knob, B-C and E-F loops on VP3 scattering around the three-fold axis of viral particle. Additional highly conserved epitopes also involved key residues of VP158, VP1147 and both VP272 / VP1147 as determined respectively by bnAb W153, W145 and W151-resistant mutants. Furthermore, the epitopes recognized by 20 strain-specific neutralization antibodies involved the key residues located on VP3 68 for A/AF72 (11/20) and VP3 175 position for A/GDMM/2013 (9/19), respectively, which revealed antigenic variation between different strains of serotype A. Analysis of antibody-driven variations on capsid of two virus strains showed a relatively stable VP2 and more variable VP3 and VP1. This study provided important information on conserve and variable antigen structures to design broad-spectrum molecular vaccine against FMDV serotype A.
Real-world effectiveness of fremanezumab for the preventive treatment of migraine: Interim analysis of the pan-European, prospective, observational, phase 4 PEARL study

Background The ongoing Pan-European Real Life (PEARL) phase 4 study is evaluating fremanezumab effectiveness and safety for the prevention of episodic and chronic migraine. This interim analysis reports primary, secondary and exploratory endpoints from when 500 participants completed at least six months of treatment. Methods Adults with episodic migraine or chronic migraine maintaining daily headache diaries were enrolled upon initiation of fremanezumab. Primary endpoint: proportion of participants with ≥50% reduction in monthly migraine days during the six-month period after fremanezumab initiation. Secondary endpoints: mean change from baseline across months 1–12 in monthly migraine days, acute migraine medication use, and headache-related disability. Exploratory endpoint: mean change in headache severity from baseline across months 1–12. Safety was assessed through adverse events reported. Results Overall, 897 participants were enrolled and 574 included in the effectiveness analyses (episodic migraine, 25.8%; chronic migraine, 74.2%). Of participants with data available, 175/313 (55.9%) achieved ≥50% monthly migraine days reduction during the six-month period post-initiation. Across months 1–12, there were sustained reductions in mean monthly migraine days, acute medication use, disability scores, and headache severity. Few adverse events were reported. Conclusion PEARL interim results support the effectiveness and safety of fremanezumab for migraine prevention in a real-world population across several European countries. Trial registration: encepp.eu: EUPAS35111
Microbiological quality of drinking water in public and municipal drinking water supply systems in Osijek-Baranja County, Croatia

original scientific paper Summary Microbiological and chemical quality of drinking water primarily results from water origin and type of applied water treatment. Since the drinking water is one of the mean way through which many infectious agents can be transmitted to humans causing waterborne diseases, constant monitoring of drinking water quality in water supply systems is needed. This study investigates the microbiological quality of drinking water in twenty five public and municipal water supply systems in the area of Osijek-Baranja County in eastern Croatia. The microbiological analyses were conducted for following parameters: total coliforms, Escherichia coli , colony count at 22 °C and 37 °C, enterococci and Clostridium perfringens . In most of investigated water supply systems processed groundwater are used, and since increased concentrations of some chemical compounds in water can influence on appearance and growth of microbiological populations, in this study relevant physicochemical parameters were also measured and correlated with obtained values of analyzed microbiological parameters. Five physicochemical indicators were determined: temperature, turbidity, pH value, free residual chlorine and ammonium concentration. Results indicated that 149 of 1503 analyzed drinking water samples were non -compliance with microbiological criteria set by Croatian regulations (88.7 % and 89.2 % of 149 had values of colony count at 22 °C and 37 °C higher than the required). Total coliforms, enterococci and Escherichia coli were founded in 3.9 %, 1.1 % and 1 % of non -compliance drinking water samples, respectively. Clostridium perfringens was not detected in any of the drinking water samples. Calculating Pearson's coefficients of correlation among analyzed microbiological and physicochemical indicators, very weak correlations were obtained. The highest but negative correlation was observed between appearance of microbiological population and concentrations of free residual chlorine (lower free residual chlorine - higher appearance of microbiological population) and positive correlation between turbidity and appearance of microbiological population (higher turbidity - higher appearance of microbiological population).
Nutrient Assimilation Services for Water Quality Credit Trading Programs

Water quality trading programs envision regulated point sources meeting discharge control requirements and then being allowed to increase their nutrient discharge if they secure nutrient reduction credits from other pollutant sources in the watershed. Reduction credits can be created when agricultural land managers implement best management practices and regulators predict that those practices will result in water quality conditions equivalent to controlling discharges at the regulated source. However, natural variability in runoff combines with model and data limitations to make predictions of water quality equivalence uncertain. Nutrient assimilation credits can be created by increasing the capacity of the ecosystem to assimilate nutrients through investments in aquatic plant biomass creation and harvest, shellfish aquaculture, stream restoration, and wetlands restoration and creation. Nutrient assimilation credits can provide greater certainty than agricultural best management practices that trading will result in equivalent water quality. Such credits should be an option in trading programs.
Incidence and predictors of respiratory distress syndrome among low birth weight neonates in the first seven days in Northwest Ethiopia Comprehensive Specialized Hospitals, 2023: A retrospective follow-up study

Introduction Respiratory distress syndrome is a catastrophic respiratory problem among low birth weight neonates. It increases the suffering of neonates and the economic expenditure of the countries. Notably, it is a major public health issue in low-income and middle-income countries such as Ethiopia. Despite this, studies regarding respiratory distress syndrome among low birth weight neonates were limited in Ethiopia. Objective To assess the incidence and predictors of respiratory distress syndrome among low birth weight neonates in the first 7 days in Northwest Ethiopia Comprehensive Specialized Hospitals. Method Multicentred institution-based retrospective follow-up study was conducted from 19 September 2021 to 1 January 2023, among 423 low birthweight neonates. A simple random sampling technique was used. The data were collected using a data extraction checklist from the medical registry of neonates. The collected data were entered into EPI-DATA V.4. 6.0. 6. and analysed using STATA V.14. The Kaplan-Meier failure curve and log-rank test were employed. Bivariable and multivariable Weibull regression was carried out to identify predictors of respiratory distress syndrome. Statistical significance was declared at a p≤0.05. Result The incidence rate of respiratory distress syndrome was found to be 10.78 (95% CI 9.35 to 12.42) per 100 neonate days. Fifth minute Appearance, Pulse, Grimace, Activity, Respiration (APGAR score) <7 (AHR 1.86; 95% CI 1.18 to 2.92), multiple pregnancy (AHR 1.43; 95% CI 1.04 to 1.96), caesarean section delivery (AHR 0.62; 95% CI 0.41 to 0.93), prematurity (AHR 1.56; 95% CI 1.06 to 2.30) and birth weight <1000 g (AHR 3.14; 95% CI 1.81 to 5.40) and 1000–1499 g (AHR 2.06; 95% CI 1.42 to 2.83) were significant predictors. Conclusion The incidence of respiratory distress syndrome was higher than other studies conducted on other groups of neonates. Multiple pregnancy, fifth minute APGAR score, caesarean section, prematurity, extremely low birth weight and very low birth weight were predictors of respiratory distress syndrome. However, it needs further prospective study. Therefore, the concerned stakeholders should give due attention and appropriate intervention for these predictors.
DURATION OF REHABILITATION THERAPY TO ACHIEVE A MINIMAL CLINICALLY IMPORTANT DIFFERENCE IN MOBILITY, WALKING ENDURANCE AND PATIENT-REPORTED PHYSICAL HEALTH: AN OBSERVATIONAL STUDY

Objective To compare the duration of exercise therapy needed to achieve a minimal clinically important difference in mobility, walking endurance and patient-reported global physical health in patients referred for inpatient rehabilitation after knee surgery, hip surgery, or with multiple sclerosis or Parkinson’s disease. Design Retrospective pre-post intervention observational cohort study. Subjects A total of 388 patients (57% women, mean age 65.6 years (standard deviation 9.5)) with a minimum length of stay 10 days were included between 1 January 2020 and 30 April 2021. Methods Outcomes were assessed at the start of, and discharge from, rehabilitation, using the following measures: mobility (Timed Up and Go test), walking endurance (6-minute walk test), patient-reported global physical health (Global Physical Health subscale of the 10-item Patient-Reported Outcomes Measurement Information System). The duration of exercise therapy needed to achieve a minimal clinically important difference was determined using anchor-based and distribution-based methods. Results The duration of therapy needed to achieve a minimal clinically important difference was longer in patients with multiple sclerosis or Parkinson’s disease (18–88 h) than in patients after knee or hip surgery (8–25 h). In all patient groups, the duration of exercise therapy needed, determined using the distribution-based method, was shortest for patient-reported global physical health (knee surgery 9.6 h, hip surgery 6.8 h, multiple sclerosis 38.7 h, Parkinson’s disease 18.4 h). Conclusion The duration of active therapies required to achieve a minimal clinically important difference in physical outcomes varies widely (range 8–88 h) among different patient groups and outcomes. LAY ABSTRACT This study in an inpatient rehabilitation setting evaluated the duration of exercise therapy needed to achieve a clinically important difference in 3 outcome measures: mobility, walking endurance, and patient-reported global physical health. Results were compared between 4 groups: patients who had undergone knee surgery; patients who had undergone hip surgery; patients with multiple sclerosis; and those with Parkinson’s disease. The exercise duration required ranged from 8 to 88 h and was longer in patients with multiple sclerosis or Parkinson’s disease, which are chronic progressive neurological conditions, compared with patients who had had knee or hip surgery. In all groups, the duration of exercise therapy required to achieve a clinically important difference was shortest for patient-reported global physical health compared with mobility and walking endurance.
Prior exposure to antiretroviral therapy among adult patients presenting for HIV treatment initiation or reinitiation in sub-Saharan Africa: a systematic review

Objectives As countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate treatment with prior ART experience. Little is known about the proportion of non-naïve reinitiators within the population presenting for treatment initiation. Design Systematic review of published articles and abstracts reporting proportions of non-naïve adult patients initiating ART in sub-Saharan Africa. Data sources PubMed, Embase Elsevier, Web of Science Core Collection, International AIDS Society conferences, Conference on Retroviruses and Opportunistic Infections conferences. Eligibility criteria Clinical trials and observational studies; reporting on adults in sub-Saharan Africa who initiated lifelong ART; published in English between 1 January 2018 and 11 July 2023 and with data collected after January 2016. Initiator self-report, laboratory discernment of antiretroviral metabolites, and viral suppression at initiation or in the medical record were accepted as evidence of prior exposure. Data extraction and synthesis We captured study and sample characteristics, proportions with previous ART exposure and the indicator of previous exposure reported. We report results of each eligible study, estimate the risk of bias and identify gaps in the literature. Results Of 2740 articles, 11 articles describing 12 cohorts contained sufficient information for the review. Proportions of initiators with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample). The vast majority of screened studies did not report naïve/non-naïve status. Metrics used to determine and report non-naïve proportions were inconsistent and difficult to interpret. Conclusions The proportion of patients initiating HIV treatment who are truly ART naïve is not well documented. It is likely that 20%–50% of ART patients who present for ART are reinitiators. Standard reporting metrics and diligence in reporting are needed, as is research to understand the reluctance of patients to report prior ART exposure. PROSPERO registration number CRD42022324136.
Global Warming and Adaptive Changes of Forest Pests

The temperature changes of six zones in China showed that atmospheric warming significantly affected the occurrence,distribution and damage of forest pests.Climate warming increases the annual accumulated temperature available for forest pests,leading to the increase of generations in some pests.It also expands the suitable temperature region for pests,resulting in the expansion of distribution area.The increase of average annual temperature leads to the advance of post-hibernant in Spring and overwintering and the delay in Autumn,then enables adults to emerge earlier,extends occurrence period,increases population,and aggravates damage.
High prevalence of vertebral fractures associated with preoperative cortisol levels in patients with recent diagnosis of Cushing disease

Abstract Background/objective Morphometric vertebral fractures (VFs) and osteopathy are prevalent and clinically significant complications of Cushing disease (CD). However whether they represent an early occurrence in the natural progression of the disease is an ongoing debate. This study aimed to assess the prevalence and determinants of VFs in patients newly diagnosed with CD. Patients and methods This cross-sectional case–control study recruited 75 newly diagnosed CD patients and compared them with a control group of individuals without pituitary disorders or secondary forms of osteoporosis. Demographic, clinical and biochemical data were collected. The VFs were assessed using preoperative lateral chest radiography. Results We found a significantly higher prevalence of VFs in the CD group than in the control group (58.7% vs. 14.5%; P < 0.001). Among the CD patients with VFs, 27 (61.4%) showed moderate/severe VFs. The CD patients with VFs had significantly higher preoperative 8 am serum cortisol (8ASC) levels than those without VFs (P < 0.001). The preoperative 4 pm adrenocorticotropic hormone (ACTH) levels (P = 0.031), preoperative 0 am ACTH levels (P = 0.021) and systolic blood pressure were slightly higher in CD patients with VFs than in those without VFs (P = 0.028). A binary multiple logistic analysis showed that 8ASC was an independent predictor of VF risk (P = 0.003). The optimal cut-off value of the preoperative serum 8ASC level for predicting VFs was 22.18 ng/mL. Conclusions This is the first study reporting a high prevalence of radiologic VFs in recently diagnosed CD patients. VFs may represent an early manifestation of CD and may be related to cortisol levels. Therefore, VF assessment should be included in the workup during CD diagnosis.
Centriole elimination during Caenorhabditis elegans oogenesis initiates with loss of the central tube protein SAS‐1

In most metazoans, centrioles are lost during oogenesis, ensuring that the zygote is endowed with the correct number of two centrioles, which are paternally contributed. How centriole architecture is dismantled during oogenesis is not understood. Here, we analyze with unprecedent detail the ultrastructural and molecular changes during oogenesis centriole elimination in Caenorhabditis elegans. Centriole elimination begins with loss of the so‐called central tube and organelle widening, followed by microtubule disassembly. The resulting cluster of centriolar proteins then disappears gradually, usually moving in a microtubule‐ and dynein‐dependent manner to the plasma membrane. Our analysis indicates that neither Polo‐like kinases nor the PCM, which modulate oogenesis centriole elimination in Drosophila, do so in C. elegans. Furthermore, we demonstrate that the central tube protein SAS‐1 normally departs initially from the organelle, which loses integrity earlier in sas‐1 mutants. Overall, our work provides novel mechanistic insights regarding the fundamental process of oogenesis centriole elimination.
Methods for gap filling in long term meteorological series and correlation analysis of meteorological networks

Climate data are very useful in many fields of the scientific research. Nowadays, in many cases these data are available through giant data-base that are often yielded by automatic meteorological networks. In order to make possible research analysis and the running of computational models, these data base need to be validated, homogenized, and to be without missing values. Validation and homogenization are common operations, nowadays: the organizations that manage these data-base provide these services. The main problem remain the reconstruction of the missing data. This dissertation deal with two main topics: (a) the reconstruction of missing values of daily precipitation and temperature datasets; (b) a base analysis on the time and space correlation between stations of a meteorological network. (a) At first, a new adaptive method to reconstruct temperature data is described. This method is compare with a non-adaptive one. A detailed analysis of the effects of the number of predictors for a regression-based approach (to reconstruct daily temperature data) and their search strategy is then presented. Precipitation and temperature are the most important climatological variables, so, a method to reconstruct daily precipitation data is chosen through a comparison of four technique. (b) The methods selected in phase (a) make it possible to reconstruct the two data-base (precipitation and temperature) that will be used for the next and last work: the correlation analysis, through time and space of network data.
GEOLOGY OF CONTINENTAL SHELF OFF LOUISIANA: ITS INFLUENCE ON OFFSHORE FOUNDATION DESIGN

Foundation problems for drilling structures offshore from Louisiana are related to the shearing strength and scour resistance of near-surface late Quaternary Continental-Shelf deposits. Over much of the shelf area, thick topstratum clays provide the foundation materials; where clays are thin, underlying substratum sands or weathered late Pleistocene deposits constitute the foundation. Study of the nature of the late Quaternary facies and of their relation to shelf topography makes it possible to map the sediment types and to date them. Compression tests on clay samples permit recognition of four categories of strength variation with depth: normally consolidated, underconsolidated approaching normal, underconsolidated, and overconsolidated clays. These tests also demonstrate that substantial time is required for clays to reach a normally consolidated condition.