Miracle-dz/UniFAR-FTUs huggingface dataset:
The forgotten people: Hepatitis B virus (HBV) infection as a priority for the inclusion health agenda

Hepatitis B virus (HBV) infection represents a significant global health threat, accounting for 300 million chronic infections and up to 1 million deaths each year. HBV disproportionately affects people who are under-served by health systems due to social exclusion, and can further amplify inequities through its impact on physical and mental health, relationship with stigma and discrimination, and economic costs. The ‘inclusion health’ agenda focuses on excluded and vulnerable populations, who often experience barriers to accessing healthcare, and are under-represented by research, resources, interventions, advocacy, and policy. In this article, we assimilate evidence to establish HBV on the inclusion health agenda, and consider how this view can inform provision of better approaches to diagnosis, treatment, and prevention. We suggest approaches to redress the unmet need for HBV interventions among excluded populations as an imperative to progress the global goal for the elimination of viral hepatitis as a public health threat.
Two oxytocin analogs, N-(p-fluorobenzyl) glycine and N-(3-hydroxypropyl) glycine, induce uterine contractions ex vivo in ways that differ from that of oxytocin

Contraction of the uterus is critical for parturient processes. Insufficient uterine tone, resulting in atony, can potentiate postpartum hemorrhage; thus, it is a major risk factor and is the main cause of maternity-related deaths worldwide. Oxytocin (OT) is recommended for use in combination with other uterotonics for cases of refractory uterine atony. However, as the effect of OT dose on uterine contraction and control of blood loss during cesarean delivery for labor arrest are highly associated with side effects, small amounts of uterotonics may be used to elicit rapid and superior uterine contraction. We have previously synthesized OT analogs 2 and 5, prolines at the 7th positions of which were replaced with N-(p-fluorobenzyl) glycine [thus, compound 2 is now called fluorobenzyl (FBOT)] or N-(3-hydroxypropyl) glycine [compound 5 is now called hydroxypropyl (HPOT)], which exhibited highly potent binding affinities for human OT receptors in vitro. In this study, we measured the ex vivo effects of FBOT and HPOT on contractions of uteri isolated from human cesarean delivery samples and virgin female mice. We evaluated the potency and efficacy of the analogs on uterine contraction, additivity with OT, and the ability to overcome the effects of atosiban, an OT antagonist. In human samples, the potency rank judged by the calculated EC50 (pM) was as follows: HPOT (189) > FBOT (556) > OT (5,340) > carbetocin (12,090). The calculated Emax was 86% for FBOT and 75% for HPOT (100%). Recovery from atosiban inhibition after HPOT treatment was as potent as that after OT treatment. HPOT showed additivity with OT. FBOT (56 pM) was found to be the strongest agonist in virgin mouse uterus. HPOT and FBOT demonstrated high potency and partial agonist efficacy in the human uterus. These results suggested that HPOT and FBOT are highly uterotonic for the human uterus and performed better than OT, indicating that they may prevent postpartum hemorrhage.
Full waveform inversion for arterial viscoelasticity

Objective. Arterial viscosity is emerging as an important biomarker, in addition to the widely used arterial elasticity. This paper presents an approach to estimate arterial viscoelasticity using shear wave elastography (SWE). Approach. While dispersion characteristics are often used to estimate elasticity from SWE data, they are not sufficiently sensitive to viscosity. Driven by this, we develop a full waveform inversion (FWI) methodology, based on directly matching predicted and measured wall velocity in space and time, to simultaneously estimate both elasticity and viscosity. Specifically, we propose to minimize an objective function capturing the correlation between measured and predicted responses of the anterior wall of the artery. Results. The objective function is shown to be well-behaving (generally convex), leading us to effectively use gradient optimization to invert for both elasticity and viscosity. The resulting methodology is verified with synthetic data polluted with noise, leading to the conclusion that the proposed FWI is effective in estimating arterial viscoelasticity. Significance. Accurate estimation of arterial viscoelasticity, not just elasticity, provides a more precise characterization of arterial mechanical properties, potentially leading to a better indicator of arterial health.
Selenium supplementation provides potent neuroprotection following cerebral ischemia in mice

Despite progress in reperfusion therapy, functional recovery remains suboptimal in many stroke patients, with oxidative stress, inflammation, dysbiosis, and secondary neurodegeneration constituting the major hurdles to recovery. The essential trace element selenium is emerging as a promising therapeutic agent for stroke. However, although several rodent studies have shown that selenium can protect against cell loss following cerebral ischemia, no study has yet examined whether selenium can enhance long-term functional recovery. Moreover, published studies have typically reported a single mechanism of action underlying selenium-mediated stroke recovery. However, we propose that selenium is more likely to have multifaceted actions. Here, we show that selenomethionine confers a potent neuroprotective effect in a canonical filament-induced transient middle cerebral artery occlusion (tMCAO) mouse model. Post-tMCAO selenium treatment significantly reduces the cerebral infarct volume, oxidative stress, and ferroptosis and enhances post-tMCAO motor performance in the acute phase after stroke. Moreover, analysis of the gut microbiota reveals that acute selenium treatment reverses stroke-induced gut dysbiosis. Longer-term selenium supplementation activates intrinsic neuroprotective mechanisms, prevents secondary neurodegeneration, alleviates systemic inflammation, and diminishes gut microbe-derived circulating trimethylamine N-oxide. These findings demonstrate that selenium treatment even after cerebral ischemia has long-term and multifaceted neuroprotective effects, highlighting its clinical potential.
Eighth case of Li‐Campeau syndrome in a Turkish patient caused by a novel pathogenic variant in UBR7 and expanding the phenotype

Li‐Campeau syndrome (LICAS) is an autosomal recessive disorder characterized by developmental delay, intellectual disability, genital anomalies, congenital heart defects, and dysmorphic features. LICAS is caused by biallelic pathogenic variants in the UBR7 gene, acting as an E3 ubiquitin‐protein ligase. Using exome sequencing (ES), we identified a homozygous novel pathogenic splice site variation c.1185+1G>C in UBR7 in a 32‐month‐old male from a nonconsanguineous Turkish family with clinical features of LICAS. Sanger sequencing revealed the heterozygous state of parents for this variant and confirmed the co‐segregation study. The variant may lead to the loss of function of UBR7 and is in a highly conserved residue. Bioinformatic prediction analysis using in silico algorithms supports the pathogenic effect of the splice site variant in the UBR7.
Why We Gather: A New Look, Empirically Documented, at Émile Durkheim’s Theory of Collective Assemblies and Collective Effervescence

For Durkheim, individuals’ survival and well-being rest on cultural resources and social belonging that must be revived periodically in collective assemblies. Durkheim’s concern was to clarify how these assemblies achieve this revitalization. An intensive examination of primitive religions led him to identify successive levels of engagement experienced by participants and to develop explanatory principles relevant to all types of collective gatherings. Durkheim’s conception is widely referred to nowadays. However, the question of its empirical status remains open. We extracted from his text his main statements and translated them into research questions. We then examined each question in relation to current theories and findings. In particular, we relied on the plethora of recent cognitive and social-psychology studies that document conditions of reduced self-other differentiation. Abundant data support that each successive moment of collective assemblies contributes to blurring this differentiation. Ample support also exists that because shared emotions are increasingly amplified in collective context, they can fuel high-intensity experiences. Moreover, recent studies of self-transcendent emotions can account for the self-transformative effects described by Durkheim at the climax of collective assemblies. In conclusion, this century-old model is remarkably supported by recent results, mostly collected in experimental settings.
Functional Changes in GABA and Glutamate during Motor Learning

Abstract Functional magnetic resonance spectroscopy (fMRS) of GABA at 3 T poses additional challenges compared with fMRS of other metabolites because of the difficulties of measuring GABA levels; GABA is present in the brain at relatively low concentrations, and its signal is overlapped by higher concentration metabolites. Using 7 T fMRS, GABA levels have been shown to decrease specifically during motor learning (and not during a control task). Though the use of 7 T is appealing, access is limited. For GABA fMRS to be widely accessible, it is essential to develop this method at 3 T. Nine healthy right-handed participants completed a motor learning and a control button-pressing task. fMRS data were acquired from the left sensorimotor cortex during the task using a continuous GABA-edited MEGA-PRESS acquisition at 3 T. We found no significant changes in GABA+/tCr, Glx/tCr, or Glu/tCr levels in either task; however, we show a positive relationship between motor learning and glutamate levels both at rest and at the start of the task. Though further refinement and validation of this method is needed, this study represents a further step in using fMRS at 3 T to probe GABA levels in both healthy cognition and clinical disorders.
Grain shattering by cell death and fracture in Eragrostis tef

Abstract Abscission, known as shattering in crop species, is a highly regulated process by which plants shed parts. Although shattering has been studied extensively in cereals and a number of regulatory genes have been identified, much diversity in the process remains to be discovered. Teff (Eragrostis tef) is a crop native to Ethiopia that is potentially highly valuable worldwide for its nutritious grain and drought tolerance. Previous work has suggested that grain shattering in Eragrostis might have little in common with other cereals. In this study, we characterize the anatomy, cellular structure, and gene regulatory control of the abscission zone (AZ) in E. tef. We show that the AZ of E. tef is a narrow stalk below the caryopsis, which is common in Eragrostis species. X-ray microscopy, scanning electron microscopy, transmission electron microscopy, and immunolocalization of cell wall components showed that the AZ cells are thin walled and break open along with programmed cell death (PCD) at seed maturity, rather than separating between cells as in other studied species. Knockout of YABBY2/SHATTERING1, documented to control abscission in several cereals, had no effect on abscission or AZ structure in E. tef. RNA sequencing analysis showed that genes related to PCD and cell wall modification are enriched in the AZ at the early seed maturity stage. These data show that E. tef drops its seeds using a unique mechanism. Our results provide the groundwork for understanding grain shattering in Eragrostis and further improvement of shattering in E. tef.
Mutation Spectrum in Liquid Versus Solid Biopsies From Patients With Advanced Gastroenteropancreatic Neuroendocrine Carcinoma

PURPOSE Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are rare and have a poor prognosis. Most GEP-NEC are diagnosed with metastatic disease, with only minor biopsies available for molecular diagnostics. We assessed the applicability of liquid biopsies for molecular profiling of GEP-NEC. MATERIALS AND METHODS We performed massive parallel sequencing of 76 cancer-related genes in circulating tumor DNA from 50 patients with advanced GEP-NEC and compared findings to previous analyses of solid tumor biopsies from the same patients. Plasma samples were collected before therapy, and the median time span between blood and tissue sampling was 25 days. RESULTS We detected 178 somatic mutations in the liquid biopsies, 127 (71%) were also detected in the solid biopsies, whereas 51 (29%) were unique to the liquid biopsies. In the same 76 genes, we previously detected 199 somatic mutations (single nucleotide variants) in solid biopsies, of which 127 (64%) were also now detected in liquid biopsies. In exploratory subgroup assessments, concordance was higher in patients with liver metastases (P = 1.5 × 10–5) and increasing with level of liver involvement (P = 1.2 × 10–4). The concordance was similar between GEP-NEC with different primary sites, except being lower in esophageal cases (P = .001). Concordance was not associated with tumor mutation burden. Tumor tissue mutations also detected in liquid biopsies was lower for MSI (40%) versus MSS tumors (70%; P = 7.8 × 10–4). We identified potentially targetable mutations in plasma of 26 (52%) of patients with GEP-NEC; nine patients (18%) had potentially targetable mutation detected only in liquid biopsies. CONCLUSION Liquid biopsy analyses may be an applicable alternative to solid biopsies in GEP-NEC. Liquid biopsies may add additional mutations compared with tumor biopsies alone and could be useful for biomarker assessment in clinical trials for these patients.
Investigation of quantitative polychromatic x-ray phase-contrast tomography for tissue characterization

At diagnostic X-ray energies, variations in the real component of the refractive index of tissues are several orders of magnitude larger than variations in the imaginary component, or equivalently, the X-ray attenuation coefficient. Consequently, X-ray phase-contrast imaging may permit the visualization of tissues that have identical, or very similar, X-ray absorption properties. Quantitative in-line phase-contrast tomography methods seek to reconstruct the three-dimensional (3D) complex X-ray refractive index distribution of tissue. Almost all existing image reconstruction algorithms for quantitative phase-contrast tomography make physical assumptions that are not consistent with benchtop or clinical implementations that employ an X-ray tube. Such assumptions include a monochromatic plane-wave X-ray beam that possesses perfect coherence properties. In this work, we implement and investigate a reconstruction theory for quantitative phase-contrast tomography that is suitable for use with polychromatic X-ray beams produced by a tube source. An image reconstruction algorithm is implemented that requires, as input data, two intensity measurements at each tomographic view that correspond to incident X-ray beams with distinct coherence properties. Computer-simulation studies that emulate polychromatic tube-based imaging conditions are conducted to assess the effectiveness of the reconstruction method for characterizing soft tissue structures.
DNA repair in cardiomyocytes is critical for maintaining cardiac function in mice

Heart failure has reached epidemic proportions in a progressively ageing population. The molecular mechanisms underlying heart failure remain elusive, but evidence indicates that DNA damage is enhanced in failing hearts. Here, we tested the hypothesis that endogenous DNA repair in cardiomyocytes is critical for maintaining normal cardiac function, so that perturbed repair of spontaneous DNA damage drives early onset of heart failure. To increase the burden of spontaneous DNA damage, we knocked out the DNA repair endonucleases xeroderma pigmentosum complementation group G (XPG) and excision repair cross‐complementation group 1 (ERCC1), either systemically or cardiomyocyte‐restricted, and studied the effects on cardiac function and structure. Loss of DNA repair permitted normal heart development but subsequently caused progressive deterioration of cardiac function, resulting in overt congestive heart failure and premature death within 6 months. Cardiac biopsies revealed increased oxidative stress associated with increased fibrosis and apoptosis. Moreover, gene set enrichment analysis showed enrichment of pathways associated with impaired DNA repair and apoptosis, and identified TP53 as one of the top active upstream transcription regulators. In support of the observed cardiac phenotype in mutant mice, several genetic variants in the ERCC1 and XPG gene in human GWAS data were found to be associated with cardiac remodelling and dysfunction. In conclusion, unrepaired spontaneous DNA damage in differentiated cardiomyocytes drives early onset of cardiac failure. These observations implicate DNA damage as a potential novel therapeutic target and highlight systemic and cardiomyocyte‐restricted DNA repair‐deficient mouse mutants as bona fide models of heart failure.
Necessary and sufficient conditions on the properiety of posterior distributions for generalized linear mixed models

This paper investigates the properties of the posterior distribution for a generalized linear mixed model (GLMM) using an improper uniform prior for the regression parameters. Necessary and sufficient conditions for the propriety of the posterior distribution with a general link function and a general covariance structure for random effects are obtained. Several special cases, including GLMM's with structured covariances for random effects and binary matched pairs data models, are also considered. Necessary theories are provided, and a real data example is used to demonstrate that the theorems can be applied to obtain proper posteriors.
Copying fideliy of functional and non-functional features in ni-Vanuatu children: A transmission chain study

Observational learning plays a key role in cultural transmission. Previous transmission chain experiments have shown that children are able to maintain information across multiple generations through observational learning. It still remains unclear how the transmission of functional vs. non-functional information and the effect of being observed unfold across age in different communities. Here, we examine children’s copying fidelity in observational learning of 5- to 13-year-olds from five different communities in Vanuatu, both individually (n = 263, 144 boys) and throughout a transmission chain of five to six children (n = 324, 178 boys). We additionally varied the functionality of the feature being copied (shape vs. color) and the copying context (observed vs. unobserved). Further, we also study developmental and cultural variation in the interaction of features and conditions. We find that children transmit the functional feature shape more faithfully than the non-functional feature color, both in the dyadic transitions as well as the transmission chains with an increasing tendency to do so as they get older. The age patterns show greater variation between communities for color than for shape. Overall, we find that being observed shows no uniform effects but influences transmission differently across communities. Our study shows that children are prone to passing on a functional feature across multiple generations of peers. Children copy non-functional features as well, but with lower fidelity. In sum, our results show children’s high propensity and developing abilities for observational learning, ultimately allowing for effective cultural transmission.
Continuous glucose monitoring in acute ischemic stroke patients treated with endovascular therapy: A pilot study to assess feasibility and accuracy

Introduction Hyperglycemia is common in acute ischemic stroke and is associated with larger infarct volume and unfavorable functional outcome, also in patients who undergo reperfusion therapy. Hyperglycemia during reperfusion may be a therapeutic target. However, previous randomized trials on the effect of glucose lowering in the acute phase of ischemic stroke failed to demonstrate effects on clinical outcome. Inaccurate glucose measurements and not focussing on patients who undergo reperfusion therapy are possible explanations. Our aim was to study the feasibility and accuracy of continuous glucose monitoring (CGM) in patients with acute ischemic stroke undergoing endovascular treatment (EVT). Methods All consecutive patients with ischemic stroke and large vessel occlusion (LVO) of the anterior circulation who were eligible for endovascular therapy within 24 hours of symptom onset and presenting at the emergency department of Isala Hospital Zwolle, the Netherlands, were enrolled in this study. CGM was performed using a Freestyle Libre Flash 2 device (FSL-CGM, Abbot Diabetes Care, Alameda, California, USA) which was implanted on arrival at the emergency department. Feasibility was defined as the number of patients who could be registered for 24 hours and delay in door-to-groin time because of sensor implantation. Accuracy of CGM versus capillary and venous based plasma glucose values was determined with the Parkes error grid analysis. Results Twenty-three patients were included of whom 20 completed 24 hours monitoring (87%). One patient did not give permission to use the data; one sensor broke during implantation and one meter was broken after a sensor was shot in so no measurements could be recorded. There was no significant delay in treatment due to implantation of the sensor and no adverse events. One hundred percent of CGM data are in zones A and B of the Parkes error grid analysis so data out of the sensor can be interpreted as accurate. Conclusion In this study, we showed that continuous glucose monitoring in patients with acute ischemic stroke due to large vessel occlusion of the anterior circulation in patients who were treated with endovascular therapy is feasible, safe and accurate.