Miracle-dz/UniFAR-FTUs huggingface dataset:
Henipaviruses—A constant threat to livestock and humans

In this review, we highlight the risk to livestock and humans from infections with henipaviruses, which belong to the virus family Paramyxoviridae. We provide a comprehensive overview of documented outbreaks of Nipah and Hendra virus infections affecting livestock and humans and assess the burden on the economy and health systems. In an increasingly globalized and interconnected world, attention must be paid to emerging viruses and infectious diseases, as transmission routes can be rapid and worldwide.
The shifts in the structure of the prokaryotic community of mountain-grassland soil under the influence of artificial larch plantations

Creation of artificial forest plantations on a global scale is one of the ways to mitigate the negative effects of climate change on ecosystems, at the same time providing soil protection from erosion, regulation of the hydrological regime and carbon sequestration in soils of different natural and climatic zones. However, the change of the dominant plant community cause significant ecosystem changes, reflecting at the structure and functioning of the soil microbial complex as well. The shifts in prokaryotic community of the meadow soil resulting from the conversion of the native meadow (further grassland) phytocenosis to the artificial forest plantations was investigated with the use of NGS sequencing technology and metabarcoding approach–amplicon sequencing of V4 region of 16 S rRNA (performed on Illumina Miseq platform). The identified shifts in taxonomic structure and diversity may be the result of changes in the physic-chemical conditions of soils and, on the other hand, may serve as indicators of such changes. Cultivation of larch led to an increase in the diversity of the prokaryotic community and its stratification by depth. The acidifying effect of larch manifested itself in an increase in the proportion and diversity of acidobacteria, in the abundance of oligotrophic microorganisms of phyla Chloroflexi, Firmicutes, and a simultaneous comparative decrease in the bacteria of Verrucomicrobia phylum, alphaproteobacteria of or. Rhizobiales and Burkholderiales. The absence of clearly expressed dominants in the prokaryotic community, as well as a significant increase in alpha-diversity indices, compared with the control plot of native mountain-meadow soil under grassland vegetation, suggests a transitional nature of the soil ecosystem of artificial forest plantations.
A supertree of Northern European macromoths

Ecological and life-history data on the Northern European macromoth (Lepidoptera: Macroheterocera) fauna is widely available and ideal for use in answering phylogeny-based research questions: for example, in comparative biology. However, phylogenetic information for such studies lags behind. Here, as a synthesis of all currently available phylogenetic information on the group, we produce a supertree of 114 Northern European macromoth genera (in four superfamilies, with Geometroidea considered separately), providing the most complete phylogenetic picture of this fauna available to date. In doing so, we assess those parts of the phylogeny that are well resolved and those that are uncertain. Furthermore, we identify those genera for which phylogenetic information is currently too poor to include in such a supertree, or entirely absent, as targets for future work. As an aid to studies involving these genera, we provide information on their likely positions within the macromoth tree. With phylogenies playing an ever more important role in the field, this supertree should be useful in informing future ecological and evolutionary studies.
Quantitative modeling identifies critical cell mechanics driving bile duct lumen formation

Biliary ducts collect bile from liver lobules, the smallest functional and anatomical units of liver, and carry it to the gallbladder. Disruptions in this process caused by defective embryonic development, or through ductal reaction in liver disease have a major impact on life quality and survival of patients. A deep understanding of the processes underlying bile duct lumen formation is crucial to identify intervention points to avoid or treat the appearance of defective bile ducts. Several hypotheses have been proposed to characterize the biophysical mechanisms driving initial bile duct lumen formation during embryogenesis. Here, guided by the quantification of morphological features and expression of genes in bile ducts from embryonic mouse liver, we sharpened these hypotheses and collected data to develop a high resolution individual cell-based computational model that enables to test alternative hypotheses in silico. This model permits realistic simulations of tissue and cell mechanics at sub-cellular scale. Our simulations suggest that successful bile duct lumen formation requires a simultaneous contribution of directed cell division of cholangiocytes, local osmotic effects generated by salt excretion in the lumen, and temporally-controlled differentiation of hepatoblasts to cholangiocytes, with apical constriction of cholangiocytes only moderately affecting luminal size.
Age-specific effectiveness of a tuberculosis screening intervention in children

Objective To apply a cascade-of-care framework to evaluate the effectiveness—by age of the child—of an intensified tuberculosis patient-finding intervention. Design From a prospective screening program at four hospitals in Pakistan (2014–2016) we constructed a care cascade comprising six steps: screened, positive screen, evaluated, diagnosed, started treatment, and successful outcome. We evaluated the cascade by each year of age from 0 to 14 and report the age-specific mean proportion and standard deviation. Results On average across all ages, only 12.5% (standard deviation: 2.0%) of children with a positive screen were not evaluated. Among children who had a complete evaluation, the highest percentages of children diagnosed with tuberculosis were observed in children 0–4 (mean: 31.9%; standard deviation: 4.8%), followed by lower percentages in children 5–9 (mean: 22.4%; standard deviation: 2.2%), and 10–14 (mean: 26.0%; standard deviation:5.4%). Nearly all children diagnosed with tuberculosis initiated treatment, and an average of 93.3% (standard deviation: 3.3%) across all ages had successful treatment outcomes. Conclusions This intervention was highly effective across ages 0–14 years. Our study illustrates the utility of applying operational analyses of age-stratified cascades to identify age-specific gaps in pediatric tuberculosis care that can guide future, novel interventions to close these gaps.
Aluminum Intoxication in Chronic Kidney Disease

2.1 Treatment of Al intoxication regardless of the dialysis modality should be done with DFO mesylate, at a single dose of 5 mg/kg/ week, intravenously, for 30 to 60 minutes, over a period of 6 months (Evidence). 2.1.1 For hemodialysis patients, DFO should be administered after the end of the first or second hemodialysis session of the week (Opinion). 2.1.1. 1 For patients with serum Al levels > 100 μg/L, DFO should be administered 5 hours prior to the start of the first hemodialysis session of the week (Opinion).
A fuzzy control system for stabilizing combustion of destructor

The main factors, affecting the combustion stability of destructor, were analyzed in the paper. By taking into account the changeful of rubbish ingredients and non-linearity, time variation and unsteadiness of burning process in destructor, the fuzzy control model for the destructor was proposed in the paper. A fuzzy controller was designed and applied in the retrofitting of control system of Shenzhen Refuse Incineration and Multi-treatment Plant. The operation result of destructor showed that the combustion stability was obviously improved, temperature variation was small, with better effect achieved.
Mucosal defect closure using a calibrated, small-caliber-tip, transparent hood after colorectal endoscopic submucosal dissection

Complete closure of a mucosal defect using a clip with a transparent cylindrical hood reduces the occurrence of adverse incidents after colorectal endoscopic submucosal dissection (ESD) [1]. Thus, we developed the “reopenable clip over the line method” (ROLM), a technique that uses a line and a reopenable clip (SureClip, 16 mm; MC Medical, Tokyo, Japan) to close a mucosal defect after ESD [2]. With the ROLM, the mucosal defect can be closed completely without clipping its edges on both sides [3]. However, when a cylindrical hood is used, there is a risk that the clip could enter the hood and impede the endoscopic view (▶Fig. 1 a, b). For this reason, we performed the ROLM using a calibrated, small-caliber-tip, transparent hood (CAST hood; TOP, Tokyo, Japan), to prevent the clips deployed for the mucosal defect closure from interfering with the endoscopic view (▶Fig. 1 c, d). The CAST hood is a tapered hood with a 4-mm tip [4] that allows the clips that are fixed to close the mucosal defect to be deflected out of the hood by the edges of the hood. It can also be used under water to maintain the endoscopic field of view intraoperatively [5]. In our case, the patient had early rectal cancer that was completely resected by ESD. The resected mucosal defect was approximately 5 cm in size, straddled the folds, and was completely closed using the ROLM with a CAST hood (▶Fig. 2; ▶Video 1). The reopenable clips did not interfere with the endoscopic view during the ROLM. A cylindrical hood with a large diameter is not always necessary because the ROLM allows themucosal defect to be closed by grasping only the defect and the nearby muscularis propria, without grasping the edges on both sides of the mucosal defect.
Post‐Stroke Hemiplegic Rodent Evaluation: A Framework for Assessing Forelimb Movement Quality Using Kinematics

Kinematics is the gold‐standard method for measuring detailed joint motions. Recent research demonstrates that post‐stroke kinematic analysis in rats reveals reaching abnormalities similar to those seen in humans after stroke. Nonetheless, behavioral neuroscientists have failed to incorporate kinematic methods for assessing movement quality in stroke models. The availability of a user‐friendly method to assess multi‐segment forelimb kinematics models should greatly increase uptake of this approach. Here, we present a framework for multi‐segment forelimb analysis in rodents after stroke. This method greatly enhances the understanding of post‐stroke forelimb motor recovery by including several movement quality metrics often used in human clinical work, such as upper‐limb linear and angular kinematics, movement smoothness and kinetics, abnormal synergies, and compensations. These metrics may constitute a preclinical surrogate for the Fugl‐Meyer assessment of hemiplegic patients. The data obtained using this method are 83 outputs of linear and angular kinematics and kinetics. The outputs also include 24 time series of continuous data, which afford a graphical representation of the kinematics and kinetics of the reaching cycle. We show that post‐stroke rodents displayed many features resembling those seen in humans after stroke that are evident only when multi‐segment kinematics models are considered. This method expands the knowledge derived from methods constrained to paw movements to a multi‐segment forelimb movement quality framework. Moreover, it highlights the need for preclinical work to consider more sensitive measures of sensorimotor impairment and recovery as a means to enhance the interpretation of true recovery and compensation. © 2022 Wiley Periodicals LLC.
Optimization of GFAG crystal surface treatment for SiPM based TOF PET detector

Coincidence timing resolution (CTR) is an important parameter in clinical positron emission tomography (PET) scanners to increase the signal-to-noise ratio of PET images by using time-of-flight (TOF) information. Lutetium (Lu) based scintillators are often used for TOF-PET systems. However, the self-radiation of Lu-based scintillators may influence the image quality for ultra-low activity PET imaging. Recently, a gadolinium fine aluminum gallate (Ce:GFAG) scintillation crystal that features a fast decay time (∼55 ns) and no self-radiation was developed. The present study aimed at optimizing the GFAG crystal surface treatment to enhance both CTR and energy resolution (ER). The TOF-PET detector consisted of a GFAG crystal (3.0 × 3.0 × 20 mm3) and a SiPM with an effective area of 3.0 × 3.0 mm2. The timing and energy signals were extracted using a high-frequency SiPM readout circuit and then were digitized using a CAMAC DAQ system. The CTR and ER were evaluated with nine different crystal surface treatments such as partial saw-cut and chemical polishing and the 1-side saw-cut was the best choice among the treatments. The respective CTR and ER of 202 ± 2 ps and 9.5 ± 0.1% were obtained with the 1-side saw-cut; the other 5-side mechanically polished GFAG crystals had respective values which were 18 ps (9.0%) and 1.3% better than those of the all-side mechanically polished GFAG crystal. The chemically polished GFAG crystals also offered enhanced CTR and ER of about 17 ps (8.2%) and 2.1%, respectively, over the mechanically polished GFAG crystals.
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Positive Modulator of HGF/MET, Fosgonimeton, in Healthy Volunteers and Subjects with Alzheimer’s Disease: Randomized, Placebo-Controlled, Double-Blind, Phase I Clinical Trial

Background: Fosgonimeton (ATH-1017) is being developed as a first-in-class regenerative therapy for people with Alzheimer’s disease (AD) and dementia; potentially improving dementia symptoms and altering disease progression by reversing synaptic disconnection and neuronal loss. Objective: This randomized, double-blind, placebo-controlled phase I trial (NCT03298672) evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of fosgonimeton. Methods: Fosgonimeton was administered once daily via subcutaneous injection to 88 subjects. The single ascending dose study enrolled healthy young male subjects (n = 48; age, 33.4±6.3 years; dose, 2, 6, 20, 40, 60, or 90 mg); the multiple ascending dose study enrolled healthy elderly subjects (n = 29; age, 63.8±4.0 years; dose, 20, 40, 60, or 80 mg; 9-day duration); and the fixed-dose study enrolled AD subjects (n = 11; age, 69.2±7.1 years; dose, 40 mg; 9-day duration). Quantitative electroencephalogram (qEEG) and event-related potential (ERP) P300 measured neurophysiological signals following fosgonimeton treatment, supporting brain penetration and target engagement. Results: Fosgonimeton and placebo were shown to be safe and well-tolerated across all doses. Pharmacokinetic results for fosgonimeton were dose-proportional, with no sex effect or accumulation over 9 days. The main effect of fosgonimeton on qEEG was acute and sustained gamma power induction. In AD subjects, there was a significant effect toward ERP P300 latency normalization compared with placebo (p = 0.027; n = 7 at 40 mg fosgonimeton versus n = 4 placebo). Conclusion: These results support the continued development of fosgonimeton as a novel therapeutic for people with AD and dementia. The fast-onset normalization of ERP P300 latency in AD subjects suggests enhancement of synaptic function and potential procognitive effects.
Curcumin Mitigates TNFα-Induced Caco-2 Cell Monolayer Permeabilization Through modulation of NF-κB, ERK1/2 and JNK Pathways.

SCOPE This work studied the capacity of curcumin to inhibit TNFα-induced inflammation, oxidative stress, and loss of intestinal barrier integrity, characterizing the underlying mechanisms. METHODS AND RESULTS Caco-2 cell monolayers were incubated with TNFα (10 ng/ml), in the absence or presence of curcumin. TNFα caused an increase in interleukin (IL)-6 and IL-8 release which was inhibited by curcumin in a dose-dependent manner (IC50 = 3.4 μM for IL-6). Moreover, TNFα led to: i) increased ICAM-1 and NLRP3 expression; ii) increased cell monolayer permeability and decreased levels of tight junction proteins; iii) increased cellular and mitochondrial oxidant production; iv) decreased mitochondrial membrane potential and complex I-III activity; v) activation of redox-sensitive pathways, i.e., NF-κB, ERK1/2 and JNK; and vi) increased MLCK expression and phosphorylation levels of MLC. Curcumin (2-8 μM) inhibited all these TNFα-triggered undesirable outcomes, mostly showing dose-dependent effects. CONCLUSION The inhibition of NF-κB, ERK1/2 and JNK activation could be in part involved in the capacity of curcumin to mitigate intestinal inflammation, oxidant production, activation of redox-sensitive pathways, and prevention of monolayer permeabilization. These results support an action of dietary curcumin in sustaining gastrointestinal tract physiology. This article is protected by copyright. All rights reserved.
CovS inactivation reduces CovR promoter binding at diverse virulence factor encoding genes in group A Streptococcus

The control of virulence gene regulator (CovR), also called caspsule synthesis regulator (CsrR), is critical to how the major human pathogen group A Streptococcus fine-tunes virulence factor production. CovR phosphorylation (CovR~P) levels are determined by its cognate sensor kinase CovS, and functional abrogating mutations in CovS can occur in invasive GAS isolates leading to hypervirulence. Presently, the mechanism of CovR-DNA binding specificity is unclear, and the impact of CovS inactivation on global CovR binding has not been assessed. Thus, we performed CovR chromatin immunoprecipitation sequencing (ChIP-seq) analysis in the emm1 strain MGAS2221 and its CovS kinase deficient derivative strain 2221-CovS-E281A. We identified that CovR bound in the promoter regions of nearly all virulence factor encoding genes in the CovR regulon. Additionally, direct CovR binding was observed for numerous genes encoding proteins involved in amino acid metabolism, but we found limited direct CovR binding to genes encoding other transcriptional regulators. The consensus sequence AATRANAAAARVABTAAA was present in the promoters of genes directly regulated by CovR, and mutations of highly conserved positions within this motif relieved CovR repression of the hasA and MGAS2221_0187 promoters. Analysis of strain 2221-CovS-E281A revealed that binding of CovR at repressed, but not activated, promoters is highly dependent on CovR~P state. CovR repressed virulence factor encoding genes could be grouped dependent on how CovR~P dependent variation in DNA binding correlated with gene transcript levels. Taken together, the data show that CovR repression of virulence factor encoding genes is primarily direct in nature, involves binding to a newly-identified DNA binding motif, and is relieved by CovS inactivation. These data provide new mechanistic insights into one of the most important bacterial virulence regulators and allow for subsequent focused investigations into how CovR-DNA interaction at directly controlled promoters impacts GAS pathogenesis.
Anatomical prognosis after idiopathic macular hole surgery: machine learning based-predection

ABSTRACT To develop a machine learning (ML) model for the prediction of the idiopathic macular hole (MH) status at 9 months after vitrectomy and inverted flap internal limiting membrane (ILM) peeling surgery. This single center was conducted at Department A, Institute Hedi Raies of Ophthalmology, Tunis, Tunisia. The study included 114 patients. In total, 120 eyes underwent optical coherence tomography (OCT) and inverted flap ILM peeling for surgery. Then 510 B scan of macular OCT was acquired 9 months after surgery. MH diameter, basal MH diameter (b), nasal and temporal arm lengths and macular hole angle were measured. Indices including hole form factor, MH index, diameter hole index (DHI) and tractional hole, MH area index and MH volume index were calculated. Receiver operating characteristic (ROC) curves and cut‑off values were derived for each indices predicting closure or not of the MH. The area under the receiver operating characteristic curve (AUC) and kappa value were calculated to evaluate performance of the medical decision support system (MDSS) in predicting the MH closure. From the ROC curve analysis, it was derived that MH indices like MH diameter, diameter hole index (DHI), MH index, and hole formation factor were capable of successfully predicting MH closure while basal diameter, DHI and MH area index predicted none closure MH. The MDSS achieved an AUC of 0.984 with a kappa value of 0.934. Based on the preoperative OCT parameters, our ML model achieved remarkable accuracy in predicting MH outcomes after pars plana vitrectomy and inverted flap ILM peeling. Therefore, MDSS may help optimize surgical planning for full thickness macular hole patients in the future.
Prevalence of Prodromal Symptoms of Parkinson’s Disease in the Late Middle-Aged Population

Background: The prodromal phase of Parkinson’s disease (PD) can last up to 20 years and is characterized by a variety of non-motor symptoms. Objective: To determine the prevalence of a selection of non-motor symptoms known to be associated with an increased risk of developing PD in a late middle-aged population-based sample and to determine their association with motor function. Methods: At a mean age of 60.3 years, 775 subjects were recruited from the Longitudinal Aging Study Amsterdam (LASA). Hyposmia, cognitive impairment, patient-reported constipation, possible REM-sleep behavior disorder, depression, and anxiety were indexed as known PD risk factors. Additionally, 1) the PD screening questionnaire, 2) four physical performance tests, and 3) a functional limitations questionnaire, were used to determine whether the presence of two or more PD risk factors was associated with reduced motor function. Results: The prevalence of single risk factors ranged between 3 and 13%. Approximately 11% of subjects had two or more PD risk factors. Motor functioning of subjects with two or more PD risk factors was significantly worse than performance of subjects without or with a single risk factor (all p values≤0.001). Conclusion: Approximately 11% of the late middle-aged population has two or more known PD risk factors. Among these subjects self-perceived PD symptoms and reduced physical performance are more prevalent, suggesting that at least some of these subjects may be in the prodromal phase of PD.