Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and Safety of Mifepristone in the Treatment of Male US Veterans With Posttraumatic Stress Disorder

Key Points Question Is there evidence of a signal for clinical efficacy for the glucocorticoid receptor antagonist mifepristone in the treatment of male veterans with posttraumatic stress disorder? Findings In this randomized clinical trial of short-term mifepristone treatment (600 mg per day for 7 days) in 80 male veterans with posttraumatic stress disorder (41 receiving mifepristone and 39 receiving placebo), the difference in the clinical response rate to mifepristone vs placebo at 4 and 12 weeks was less than the predefined clinical margin used to define efficacy. Meaning These results do not support an indication for a phase 3 trial of this regimen in this heterogeneous population.
Evaluation of dose perturbations around iodine-125 seed sources in supplemental external beam prostate radiotherapy

Abstract We investigated dose perturbations caused by 125I seeds in patients undergoing supplemental external beam radiotherapy (EBRT) for prostate cancer. We examined two types of nonradioactive seed models: model 6711 and model STM1251. All experiments were performed using a water-equivalent phantom. Radiochromic film was used to measure the dose distributions adjacent to the seeds upstream and downstream of the external beam source. Single and clusters of multiple seeds were placed in slots in a solid water (SW) slab to measure dose perturbations with separate versus dense seed placement at beam energies of 6 or 10 MV. Monte Carlo simulations (MCSs) were also performed to include the theoretical basis against film dosimetry. Distinct patterns of dose enhancement (buildup [BU]) were upstream, and dose reduction (builddown [BD]) were downstream of the radiation source. Model 6711 with lower photon beam energies produced larger dose perturbations of BU and BD than the model STM1251. The results showed the same tendency with different seed placements and beam energies. However, these differences were not observed in the rotational irradiation measurement, which replicated a clinical plan. Dose perturbations around seeds result in dose enhancement and dose reduction with varying impact depending on the photon beam energy and seed type. This has the potential to cancel out these perturbations using multiple beam direction fields.
Analysis of single nucleotide polymorphisms associated with the vitamin D pathway in the placentas of women with gestational diabetes mellitus: a laboratory study

Background The aim of this study was to analyze the single nucleotide polymorphisms (SNPs) of genes known to be involved in vitamin D metabolism in the placenta using the placental tissue of mothers diagnosed with gestational diabetes mellitus (GDM) to determine whether the SNPs and occurrence of GDM are related. Methods We enrolled 80 women of the same gestational age, 40 with and 40 without GDM. The placenta was obtained from each woman after delivery and SNP genotyping was performed on seven SNPs in the CYP27B1 (rs10877012), CYP24A1 (rs2248359, rs6013897, and rs2209314), and GC (rs2282679, rs16847024, and rs3733359) genes. Maternal serum 25-hydroxyvitamin D levels were measured during the first trimester of pregnancy and before delivery. Results At the time of delivery, vitamin D levels were lower (21.05±12.05 mg/dL vs. 31.31±20.72 mg/dL, p=0.012) and the frequency of vitamin D deficiency was higher (60.7% vs. 32.5%, p=0.040) in the GDM group. In women with GDM, the G allele of rs10877012 was more common (86.3% vs. 65.0%, p=0.002). The rs10877012 GG genotype was more common in the GDM group (72.5% vs. 42.5%, p=0.007) and the rs10877012 TT genotype was more common in the control group (12.5% vs. 0%, p=0.007). Conclusion Mothers with GDM have lower serum concentrations of vitamin D before delivery than healthy controls and vitamin D deficiency is common. A polymorphism in CYP27B1 (rs10877012), is considered to be a cause of GDM pathogenesis.
Practical considerations for the use of SGLT‐2 inhibitors in the Asia–Pacific countries—An expert consensus statement

Recent clinical studies have demonstrated the effectiveness of SGLT‐2 inhibitors in reducing the risks of cardiovascular and renal events in both patients with and without type 2 diabetes mellitus. Consequently, many international guidelines have begun advocating for the use of SGLT‐2 inhibitors for the purpose of organ protection rather than as simply a glucose‐lowering agent. However, despite the consistent clinical benefits and available strong guideline recommendations, the utilization of SGLT‐2 inhibitors have been unexpectedly low in many countries, a trend which is much more noticeable in low resource settings. Unfamiliarity with the recent focus in their organ protective role and clinical indications; concerns with potential adverse effects of SGLT‐2 inhibitors, including acute kidney injury, genitourinary infections, euglycemic ketoacidosis; and their safety profile in elderly populations have been identified as deterring factors to their more widespread use. This review serves as a practical guide to clinicians managing patients who could benefit from SGLT‐2 inhibitors treatment and instill greater confidence in the initiation of these drugs, with the aim of optimizing their utilization rates in high‐risk populations.
Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial.

Importance The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear. Objective To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone. Design, Setting, and Participants Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019. Intervention Patients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147). Main Outcome and Measures The primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days. Results Among 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [P = .33]; between-group difference, -4.7% [95% CI, -14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, -11.8% [95% CI, -23.0% to -0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group). Conclusion and Relevance In patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis. Trial Registration ClinicalTrials.gov Identifier: NCT02281929.
Electrical Properties of YH3under High Pressure

The electrical transport properties of yttrium hydride YH x ( x ∼3) was studied by the electrical resistivity measurements at low temperature and high pressures up to 55 GPa using a diamond anvil cell. YH x was an insulator at ambient pressure and became metallic above 40 GPa. Anomalies, which may be attributed to some phase transitions, were observed in both ρ– P and ρ– T curves at 40–60 GPa and 150 K, respectively.
Gradual changes in model shape affect egg-directed behaviours by parasitic shiny cowbirds Molothrus bonariensis in captivity

Eggs are critically important for avian reproduction as all birds are oviparous. Accordingly, the recognition and care of own eggs represent the cornerstones of avian breeding, whereas the elimination of foreign objects, including brood-parasitic eggs and non-egg items from the nest are known to also increase fitness by refocusing incubation effort on the parents' own eggs. But egg recognition also plays a role in some avian obligate brood parasites' reproductive strategy through the pecking of already present eggs in the hosts' clutch to reduce nestmate competition with the parasite's own hatchling. Here we tested egg shape recognition in this parasitic egg-pecking context by exposing two different series of 3D printed models to captive obligate brood-parasitic shiny cowbirds (Molothrus bonariensis) in artificial nests. Natural egg-shaped models were pecked more often compared with increasingly thinner models, but there was no effect of increasing angularity on pecking rates, implying that a natural, rather than an artificial, range of variability elicited adaptive responses from parasitic cowbirds.
Caprin-1 binding to the critical stress granule protein G3BP1 is influenced by pH

G3BP is the central node within stress-induced protein–RNA interaction networks known as stress granules (SGs). The SG-associated proteins Caprin-1 and USP10 bind mutually exclusively to the NTF2 domain of G3BP1, promoting and inhibiting SG formation, respectively. Herein, we present the crystal structure of G3BP1-NTF2 in complex with a Caprin-1-derived short linear motif (SLiM). Caprin-1 interacts with His-31 and His-62 within a third NTF2-binding site outside those covered by USP10, as confirmed using biochemical and biophysical-binding assays. Nano-differential scanning fluorimetry revealed reduced thermal stability of G3BP1-NTF2 at acidic pH. This destabilization was counterbalanced significantly better by bound USP10 than Caprin-1. The G3BP1/USP10 complex immunoprecipated from human U2OS cells was more resistant to acidic buffer washes than G3BP1/Caprin-1. Acidification of cellular condensates by approximately 0.5 units relative to the cytosol was detected by ratiometric fluorescence analysis of pHluorin2 fused to G3BP1. Cells expressing a Caprin-1/FGDF chimera with higher G3BP1-binding affinity had reduced Caprin-1 levels and slightly reduced condensate sizes. This unexpected finding may suggest that binding of the USP10-derived SLiM to NTF2 reduces the propensity of G3BP1 to enter condensates.
Herbivorous dietary selection shown by hawfinch (Coccothraustes coccothraustes) within mixed woodland habitats

Knowledge of diet and dietary selectivity is vital, especially for the conservation of declining species. Accurately obtaining this information, however, is difficult, especially if the study species feeds on a wide range of food items within heterogeneous and inaccessible environments, such as the tree canopy. Hawfinches (Coccothraustes coccothraustes), like many woodland birds, are declining for reasons that are unclear. We investigated the possible role that dietary selection may have in these declines in the UK. Here, we used a combination of high-throughput sequencing of 261 hawfinch faecal samples assessed against tree occurrence data from quadrats sampled in three hawfinch population strongholds in the UK to test for evidence of selective foraging. This revealed that hawfinches show selective feeding and consume certain tree genera disproportionally to availability. Positive selection was shown for beech (Fagus), cherry (Prunus), hornbeam (Carpinus), maples (Acer) and oak (Quercus), while Hawfinch avoided ash (Fraxinus), birch (Betula), chestnut (Castanea), fir (Abies), hazel (Corylus), rowan (Sorbus) and lime (Tilia). This approach provided detailed information on hawfinch dietary choice and may be used to predict the effects of changing food resources on other declining passerines populations in the future.
Female–female aggression in the Gila monster (Heloderma suspectum)

Historically, the role of aggression in the social lives of animals overwhelmingly focused on males. In recent years, however, female–female aggression in vertebrates, particularly lizards, has received increasing attention. This growing body of literature shows both similarities and differences to aggressive behaviours between males. Here, we document female–female aggression in captive Gila monsters (Heloderma suspectum). Based on four unique dyadic trials (eight adult female subjects), we developed a qualitative ethogram. Unexpected and most intriguing were the prevalence and intensity of aggressive acts that included brief and sustained biting, envenomation, and lateral rotation (i.e. rolling of body while holding onto opponent with closed jaws). Given specific behavioural acts (i.e. biting) and the results of bite-force experiments, we postulate that osteoderms (bony deposits in the skin) offer some degree of protection and reduce the likelihood of serious injury during female–female fights. Male–male contests in H. suspectum, in contrast, are more ritualized, and biting is rarely reported. Female–female aggression in other lizards has a role in territoriality, courtship tactics, and nest and offspring guarding. Future behavioural research on aggression in female Gila monsters is warranted to test these and other hypotheses in the laboratory and field.
Temperature adaptation and its impact on the shape of performance curves in Drosophila populations

Understanding how species adapt to different temperatures is crucial to predict their response to global warming, and thermal performance curves (TPCs) have been employed recurrently to study this topic. Nevertheless, fundamental questions regarding how thermodynamic constraints and evolution interact to shape TPCs in lineages inhabiting different environments remain unanswered. Here, we study Drosophila simulans along a latitudinal gradient spanning 3000 km to test opposing hypotheses based on thermodynamic constrains (hotter-is-better) versus biochemical adaptation (jack-of-all-temperatures) as primary determinants of TPCs variation across populations. We compare thermal responses in metabolic rate and the egg-to-adult survival as descriptors of organismal performance and fitness, respectively, and show that different descriptors of TPCs vary in tandem with mean environmental temperatures, providing strong support to hotter-is-better. Thermodynamic constraints also resulted in a strong negative association between maximum performance and thermal breadth. Lastly, we show that descriptors of TPCs for metabolism and egg-to-adult survival are highly correlated, providing evidence of co-adaptation, and that curves for egg-to-adult survival are systematically narrower and displaced toward lower temperatures. Taken together, our results support the pervasive role of thermodynamics constraining thermal responses in Drosophila populations along a latitudinal gradient, that are only partly compensated by evolutionary adaptation.
Virulence decomposition for bifurcating infections

A fundamental goal in infection biology is to understand the emergence of variation in pathogen virulence—here defined as the decrease in host fitness caused by a pathogen. To uncover the sources of such variation, virulence can be decomposed into both host- and pathogen-associated components. However, decomposing virulence can be challenging owing to complex within-host pathogen dynamics such as bifurcating infections, which recently received increased empirical and theoretical attention. Bifurcating infections are characterized by the emergence of two distinct infection types: (i) terminal infections with high pathogen loads resulting in rapid host death, and (ii) persistent infections with lower loads and delayed host death. Here, we propose to use discrete mixture models to perform separate virulence decompositions for each infection type. Using this approach, we reanalysed a recently published experimental dataset on bacterial load and survival in Drosophila melanogaster. This analysis revealed several advantages of the new approach, most importantly the generation of a more comprehensive picture of the varying sources of virulence in different bacterial species. Beyond this application, our approach could provide valuable information for ground-truthing and improving theoretical models of within-host infection dynamics, which are developed to predict variation in infection outcome and pathogen virulence.
Delay eyeblink conditioning performance and brain-wide c-Fos expression in male and female mice

Delay eyeblink conditioning has been extensively used to study associative learning and the cerebellar circuits underlying this task have been largely identified. However, there is a little knowledge on how factors such as strain, sex and innate behaviour influence performance during this type of learning. In this study, we used male and female mice of C57BL/6J (B6) and B6CBAF1 strains to investigate the effect of sex, strain and locomotion in delay eyeblink conditioning. We performed a short and a long delay eyeblink conditioning paradigm and used a c-Fos immunostaining approach to explore the involvement of different brain areas in this task. We found that both B6 and B6CBAF1 females reach higher learning scores compared to males in the initial stages of learning. This sex-dependent difference was no longer present as the learning progressed. Moreover, we found a strong positive correlation between learning scores and voluntary locomotion irrespective of the training duration. c-Fos immunostainings after the short paradigm showed positive correlations between c-Fos expression and learning scores in the cerebellar cortex and brainstem, as well as previously unreported areas. By contrast, after the long paradigm, c-Fos expression was only significantly elevated in the brainstem. Taken together, we show that differences in voluntary locomotion and activity across brain areas correlate with performance in delay eyeblink conditioning across strains and sexes.
Improving Detection Rates for Primary Aldosteronism

Abstract Primary aldosteronism (PA), once considered a rare disease, is being increasingly recognized as an important cause of hypertension. It is associated with higher rates of cardiovascular complications compared to blood pressure-matched essential hypertension. Targeted treatments are available which can mitigate the excess cardiovascular risks and, in some cases, cure hypertension. Making a timely diagnosis of PA is, therefore, highly beneficial for patients. Furthermore, numerous studies from different parts of the world have found PA to be a relatively common disease that can affect patients in any stage of hypertension, regardless of their age or potassium levels. Despite this well-established data, the current rate of PA detection is appallingly low, much below its actual prevalence. This review explores the challenges that clinicians often face in diagnosing PA and offers strategies that may improve the detection of this potentially curable form of hypertension.
Gravitational Microlensing: GPU-based Simulation Algorithms and the Information Content of Light Curves

The simulation of gravitational microlensing light curves is a time-consuming effort, but essential for confirming potential planetary microlensing events. In this thesis a point-wise binary lens model was developed and parallelized on Graphics Processing Units (GPUs). As most graphic cards are processing single-precision floating point numbers, special care was taken to understand and control the numerical accuracy. In order to increase the efficiency of the fitting process, information theoretical concepts have been exploited. Based on the insight, that observations differently contribute to the total information content, subsets of the light curves are selected according to the current state of a Markov Chain. Furthermore, the information content of a point lens light curve was used in order to optimize the sampling of a light curve. In a further major project, follow-up observations were carried out as part of the MiNDSTEp consortium and a data reduction pipeline was prepared. The analysis of an anomalous microlensing event, observed in the season 2010, was used to test the newly developed GPU-model for fitting light curves. According to the Besancon population synthesis model of the Galaxy, a physical interpretation of the system was given, indicating that one component is likely to be a substellar object. A planetary system can be excluded for both components. The second component is either a low-mass star or a heavy brown dwarf. The work is concluded with estimates for the limiting magnitudes for two space missions, namely the Heliospheric Imagers 1 (HI 1) onboard the STEREO satellites and the planned PLATO mission, where the latter could be used for observing highly magnified microlensing events.
Multimode hybrid gold-silicon nanoantennas for tailored nanoscale optical confinement

Abstract High-index dielectric nanoantennas, which provide an interplay between electric and magnetic modes, have been widely used as building blocks for a variety of devices and metasurfaces, both in linear and nonlinear regimes. Here, we investigate hybrid metal-semiconductor nanoantennas, consisting of a multimode silicon nanopillar core coated with a gold layer, that offer an enhanced degree of control over the mode selection and confinement, and emission of light on the nanoscale exploiting high-order electric and magnetic resonances. Cathodoluminescence spectra revealed a multitude of resonant modes supported by the nanoantennas due to hybridization of the Mie resonances of the core and the plasmonic resonances of the shell. Eigenmode analysis revealed the modes that exhibit enhanced field localization at the gold interface, together with high confinement within the nanopillar volume. Consequently, this architecture provides a flexible means of engineering nanoscale components with tailored optical modes and field confinement for a plethora of applications, including sensing, hot-electron photodetection and nanophotonics with cylindrical vector beams.