Miracle-dz/UniFAR-FTUs huggingface dataset:
Male Sex Is Associated With Higher Rates of Liver‐Related Mortality in Primary Biliary Cholangitis and Cirrhosis

The impact of sex on the postcirrhosis progression of primary biliary cholangitis (PBC) has not been well defined. Prior studies have suggested that men have worse outcomes but present at more advanced stages of fibrosis than women. This observation, however, has been limited by small numbers of men and even fewer patients with cirrhosis.
Temperature-induced microstructural changes in shells of laboratory-grown Arctica islandica (Bivalvia)

Bivalve shells are increasingly used as archives for high-resolution paleoclimate analyses. However, there is still an urgent need for quantitative temperature proxies that work without knowledge of the water chemistry–as is required for δ18O-based paleothermometry–and can better withstand diagenetic overprint. Recently, microstructural properties have been identified as a potential candidate fulfilling these requirements. So far, only few different microstructure categories (nacreous, prismatic and crossed-lamellar) of some short-lived species have been studied in detail, and in all such studies, the size and/or shape of individual biomineral units was found to increase with water temperature. Here, we explore whether the same applies to properties of the crossed-acicular microstructure in the hinge plate of Arctica islandica, the microstructurally most uniform shell portion in this species. In order to focus solely on the effect of temperature on microstructural properties, this study uses bivalves that grew their shells under controlled temperature conditions (1, 3, 6, 9, 12 and 15°C) in the laboratory. With increasing temperature, the size of the largest individual biomineral units and the relative proportion of shell occupied by the crystalline phase increased. The size of the largest pores, a specific microstructural feature of A. islandica, whose potential role in biomineralization is discussed here, increased exponentially with culturing temperature. This study employs scanning electron microscopy in combination with automated image processing software, including an innovative machine learning–based image segmentation method. The new method greatly facilitates the recognition of microstructural entities and enables a faster and more reliable microstructural analysis than previously used techniques. Results of this study establish the new microstructural temperature proxy in the crossed-acicular microstructures of A. islandica and point to an overarching control mechanism of temperature on the micrometer-scale architecture of bivalve shells across species boundaries.
Cyclic 68Ga-Labeled Peptides for Specific Detection of Human Angiotensin-Converting Enzyme 2

Visual Abstract In this study, we developed angiotensin-converting enzyme 2 (ACE2)–specific, peptide-derived 68Ga-labeled radiotracers, motivated by the hypotheses that ACE2 is an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and that modulation of ACE2 in coronavirus disease 2019 (COVID-19) drives severe organ injury. Methods: A series of NOTA-conjugated peptides derived from the known ACE2 inhibitor DX600 were synthesized, with variable linker identity. Since DX600 bears 2 cystine residues, both linear and cyclic peptides were studied. An ACE2 inhibition assay was used to identify lead compounds, which were labeled with 68Ga to generate peptide radiotracers (68Ga-NOTA-PEP). The aminocaproate-derived radiotracer 68Ga-NOTA-PEP4 was subsequently studied in a humanized ACE2 (hACE2) transgenic model. Results: Cyclic DX-600–derived peptides had markedly lower half-maximal inhibitory concentrations than their linear counterparts. The 3 cyclic peptides with triglycine, aminocaproate, and polyethylene glycol linkers had calculated half-maximal inhibitory concentrations similar to or lower than the parent DX600 molecule. Peptides were readily labeled with 68Ga, and the biodistribution of 68Ga-NOTA-PEP4 was determined in an hACE2 transgenic murine cohort. Pharmacologic concentrations of coadministered NOTA-PEP (blocking) showed a significant reduction of 68Ga-NOTA-PEP4 signals in the heart, liver, lungs, and small intestine. Ex vivo hACE2 activity in these organs was confirmed as a correlate to in vivo results. Conclusion: NOTA-conjugated cyclic peptides derived from the known ACE2 inhibitor DX600 retain their activity when N-conjugated for 68Ga chelation. In vivo studies in a transgenic hACE2 murine model using the lead tracer, 68Ga-NOTA-PEP4, showed specific binding in the heart, liver, lungs and intestine—organs known to be affected in SARS-CoV-2 infection. These results suggest that 68Ga-NOTA-PEP4 could be used to detect organ-specific suppression of ACE2 in SARS-CoV-2–infected murine models and COVID-19 patients.
Deep-Learning-Based Automatic Selection of Fewest Channels for Brain–Machine Interfaces

Due to the development of convenient brain–machine interfaces (BMIs), the automatic selection of a minimum channel (electrode) set has attracted increasing interest because the decrease in the number of channels increases the efficiency of BMIs. This study proposes a deep-learning-based technique to automatically search for the minimum number of channels applicable to general BMI paradigms using a compact convolutional neural network for electroencephalography (EEG)-based BMIs. For verification, three types of BMI paradigms are assessed: 1) the typical P300 auditory oddball; 2) the new top-down steady-state visually evoked potential; and 3) the endogenous motor imagery. We observe that the optimized minimal EEG-channel sets are automatically selected in all three cases. Their decoding accuracies using the minimal channels are statistically equivalent to (or even higher than) those based on all channels. The brain areas of the selected channel set are neurophysiologically interpretable for all of these cognitive task paradigms. This study shows that the minimal EEG channel set can be automatically selected, irrespective of the types of BMI paradigms or EEG input features using a deep-learning approach, which also contributes to their portability.
Characteristics of arsenic species in cerebrospinal fluid (CSF) of acute promyelocytic leukaemia (APL) patients treated with arsenic trioxide plus mannitol

Arsenic speciation in cerebrospinal fluid (CSF) is critical for treatment/prevention of central nervous system (CNS) relapse in acute promyelocytic leukaemia (APL) patients treated with arsenic trioxide (ATO). Previous study showed low total arsenic level in CSF of APL patients. Mannitol infusion was applied to improve blood–brain barrier (BBB) permeability for arsenic. Arsenite (AsIII), monomethylarsonic acid (MMAV), dimethylarsinic acid (DMAV), and arsenate (AsV) in CSF and plasma were analysed by high performance liquid chromatography‐hydride generation‐atomic fluorescence spectrometry (HPLC‐HG‐AFS). The profile and concentration of arsenic species in CSF from APL patients administered ATO alone and in combination with mannitol were compared. The overall distribution trend of arsenic species in CSF was AsIII, DMAV > MMAV > AsV. Arsenicals accumulated in CSF with administration frequency. The permeability of BBB for AsIII was higher than that for MMAV and DMAV. Arsenic concentration in CSF was much lower than that in plasma. There were significantly higher arsenic species concentrations in CSF of APL patients treated with mannitol than that without mannitol. Mannitol infusion significantly increased AsIII penetration into CSF, which was beneficial to optimize efficacy in APL patients with CNS relapse.
Second-Order Sexual Harassment: Violence Against the Silence Breakers Who Support the Victims

Second-order sexual harassment (SOSH) is the harassment suffered by those who stand with and support victims of violence against women (VAW)1. Because the vast majority of programs currently focus on promoting bystander intervention, for such programs to be successful, knowledge about and actions against SOSH are necessary. Through narratives, this article provides unprecedented clues about SOSH. Working on safety strategies for individuals who support victims, promoting solidarity networks that also address SOSH, and ensuring that institutional policies are enforced are found to be central factors that can help prevent and/or transcend SOSH.
Dolutegravir is not associated with weight gain in antiretroviral therapy experienced geriatric patients living with HIV

Supplemental Digital Content is available in the text Objective: The aim of this study was to explore weight gain in people with HIV (PWH) at least 65 years of age who switch to a DTG based regimen (DTG-s) vs. remaining INSTI-naive (INSTI-n) on stable ART. Methods: This was a longitudinal prospective study of PWH from the GEPPO cohort. At the beginning of the observational period, participants were INSTI-naives (INSTI-n). During follow-up, they were divided in two groups: INSTI-n vs. dolutegravir-switchers (DTG-s) with no further change in ART. Body weight was assessed at baseline and at last follow-up visit. Significant weight gain was defined as an increase at least 5% of baseline weight from the first to the last visit. ART regimens were collected at each patients’ visit. Kaplan--Meier curves were drawn to assess time to reach a weight gain more than 5%. Results: Out of 568 PWH (83.1% men, median age 69.5 years), 427 (75%) were INSTI-n and 141 (25%) DTG-s. After an average follow-up of 2.6 (±0.8) years, no significant change in body weight was observed both among INSTI-n [delta weight = 0.02 (±7.5), P = 0.633] and DTG-s [delta weight = −0.04 (±5.2), P = 0.755]. Weight gain was also not significantly different between study groups (9.3% in INSTI-n and 15.1% in DTG-S: P = 0.175). No significant differences in time to achieve a weight gain greater or equal than 5% of baseline weight emerged in INSTI-n vs. DTG-s (P = 0.93), two-drug regimens (2DR) vs. three-drug regimens (3DR) (P = 0.56) or TAF vs. TDF (P = 0.56). Conclusion: Results from a large Italian cohort did not show a significant weight gain associated with switch to DTG in PWH 65 years of age or older. This finding emerged also when comparing 3DR vs. 2DR and TAF exposed and unexposed geriatric PWH.
Is the needle as risky as the knife? The prevalence and risks of body dysmorphic disorder in women undertaking minor cosmetic procedures

Objectives: Body dysmorphic disorder is commonly considered a contraindication for major cosmetic surgery, but whether body dysmorphic disorder relates to poorer outcomes from minor cosmetic treatment remains unknown. This study aimed to explore the prevalence of body dysmorphic disorder in clients seeking non-surgical cosmetic procedures and to examine whether body dysmorphic disorder clients are vulnerable in minor cosmetic settings. Vulnerability was explored in terms of psychological distress, unrealistic expectations and motivations for treatment outcome, and reduced satisfaction with past cosmetic procedures. Method: A cross-sectional online survey was completed by 154 women seeking minor cosmetic procedures which included the Body Dysmorphic Disorder Questionnaire – Dermatology Version to screen for body dysmorphic disorder, and measures of cosmetic treatment motivation, expectations and satisfaction. Results: Roughly 25% of women in the current sample screened positive for a potential body dysmorphic disorder diagnosis. Participants with suspected body dysmorphic disorder demonstrated higher levels of psychological distress and more unrealistic expectations and motivations for cosmetic treatment, such as improving social or romantic relationships. However, body dysmorphic disorder participants reported similar levels of satisfaction with past minor cosmetic treatments to the non–body dysmorphic disorder group. Conclusion: While the relationship between body dysmorphic disorder and treatment outcome warrants further investigation in prospective research tracking satisfaction and adverse reactions over time, this preliminary evidence suggests clients with suspected body dysmorphic disorder display several vulnerabilities in non-surgical cosmetic settings. Given the rapidly increasing accessibility of minor cosmetic procedures, further research is needed to determine their safety for clients with body dysmorphic disorder. Detection of body dysmorphic disorder in non-surgical cosmetic settings could facilitate earlier psychological intervention, promoting superior long-term outcomes.
Self-powered and high responsivity photodetector based on a n-Si/p-GaTe heterojunction

Heterojunction integrated by two-dimensional/three-dimensional materials has shown great potential applications in optoelectronic devices because of its fast response speed, high specific detectivity and broad spectral response. In this work, the vertical n-Si/p-GaTe heterojunction has been designed and fabricated, which shows a high responsivity up to 5.73 A W−1 and a fast response time of 20 μs at zero bias benifitting from the high efficiency of light absorption, internal photocurrent gain and strong built-in electrical field. A specific detectivity of 1012 Jones and a broad spectral response ranging from 300 to 1100 nm can also be achieved. This work provides an alternative strategy for high-performance self-powered optoelectronic devices.
Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck

The evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, undergo antigenic evolution depend on the ways genetic variation is generated and selected within and between individual hosts. Using domestic cats as a model, we show that SARS-CoV-2 consensus sequences remain largely unchanged over time within hosts, while dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which was previously shown to confer escape from human monoclonal antibodies. This variant arises rapidly and persists at intermediate frequencies in index cats. It also becomes fixed following transmission in two of three pairs. These dynamics suggest this site may be under positive selection in this system and illustrate how a variant can quickly arise and become fixed in parallel across multiple transmission pairs. Transmission of SARS-CoV-2 in cats involved a narrow bottleneck, with new infections founded by fewer than ten viruses. In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems.
Signatures of lipid assemblages in soils under continental Mediterranean forests

Summary The analysis of free lipids in 12 soils from three representative types of Mediterranean forest has been carried out in an attempt to describe diagnostic molecules reflecting differences between the ecosystems and the intensity of the soil organic matter turnover. The study centred on the analysis by gas chromatography–mass spectrometry of the soil compounds extracted with petroleum ether from soils in central Spain, developed under monospecific formations of stone pine (Pinus pined), evergreen oak (Quercus rotundifolia) and Spanish juniper (Juniperus thurifera), the lipid extracts from their leaves also being analysed as reference material. The comparison between the distribution patterns of alkanes and fatty acids in plant lipids and the corresponding soil lipids was used to assess the extent to which the former accumulate in soil or are substituted by other biogenic or diagenetic homologues. In general, the alkane patterns showed the greatest variation in soils under oak, and the differences between lipid patterns in plant and soil were greatest in the juniper forests. As indicators of the vegetation type, the soil fatty acids had little value. Up to 60 major cyclic compounds were identified, including mainly di- and sesquiterpenes, in addition to some monoterpenes and nonterpenic naphthalenes and decalins. Of these major constituents, 33 compounds were found in soil but were not present in plant extracts, and 18 compounds were identified in plants but were not in the soils. The results suggest an arrangement of the soil samples based on the composition of the signature lipid assemblages.
Semisupervised Feature Selection via Structured Manifold Learning

Recently, semisupervised feature selection has gained more attention in many real applications due to the high cost of obtaining labeled data. However, existing methods cannot solve the “multimodality” problem that samples in some classes lie in several separate clusters. To solve the multimodality problem, this article proposes a new feature selection method for semisupervised task, namely, semisupervised structured manifold learning (SSML). The new method learns a new structured graph which consists of more clusters than the known classes. Meanwhile, we propose to exploit the submanifold in both labeled data and unlabeled data by consuming the nearest neighbors of each object in both labeled and unlabeled objects. An iterative optimization algorithm is proposed to solve the new model. A series of experiments was conducted on both synthetic and real-world datasets and the experimental results verify the ability of the new method to solve the multimodality problem and its superior performance compared with the state-of-the-art methods.
Across‐species meta‐analysis of dexamethasone pharmacokinetics utilizing allometric and scaling modeling approaches

The pharmacokinetic (PK) parameters of dexamethasone (DEX) in 11 species were collected from the literature and clearances (CL) assessed by basic allometric methods, and concentration–time course profiles were fitted using two PK models incorporating physiological or allometric scaling. Plots of log CL vs. log body weights (BW) correlated reasonably with R2 = 0.91, with a maximum ratio of actual to fitted CL of 6 (for pig). A minimal physiologically‐based pharmacokinetic (mPBPK) model containing blood and two lumped tissue compartments and integrated utilization of physiological parameters was compared to an allometric two‐compartment model (a2CM). The plasma PK profiles of DEX from 11 species were analyzed jointly, with the mPBPK model having conserved partition coefficients (Kp), physiologic blood and tissue volumes, and species‐specific CL values. The DEX PK profiles were reasonably captured by the mPBPK model for 9 of 11 species in the joint analysis with three fitted parameters (besides CL) including an overall tissue‐to‐plasma partition coefficient of 1.07. The a2CM with distribution CL and central and peripheral volumes scaled allometrically fitted the plasma concentration profiles similarly but required a total of six parameters (besides CL). Overall, the literature reported that DEX CL values exhibit moderate variability (mean = 0.64 L/h/kg; coefficient of variation = 105%), but distribution parameters were largely conserved across most species.
Influence of chicory preparation containing fructans and polyphenols on nitrogen excretion patterns and ileal mineral absorption in rats.

In two experiments on Wistar rats, the influence of chicory fructans and their dietary combination with polyphenols on nitrogen excretion routes and mineral absorption in the ileum was examined. In the first experiment, during 15 days, twenty four rats were randomly divided into three equal groups of eight animals. The rats were assigned to the following diets: control (C), with 7.5% of chicory fructooligosaccharides (F), and that containing 7.5% of fructooligosaccharides combined with 0.05% of polyphenols (FP) were applied to 24 animals. In the second experiment on 30 rats, an in situ technique in an open system based on controlled flow of perfusion fluid through the small intestine of anaesthetized rats was used for assessing gut absorption. The content of fructooligosaccharides in the F fluid was 9.7 g/100 ml, while in the FP group the fluid contained similar amount of FOS and 62.5 mg of chicory polyphenols per 100 ml. Feeding fructooligosaccharides caused, typical for this type of dietary fibre, higher nitrogen excretion in faeces and lower N losses in urea as compared to the control group. Simultaneous dietary addition of polyphenols slightly increased these effects, however, the N digestibility and utilization indices did not differ significantly between F and FP groups (Experiment I). The chicory preparation containing both fructooligosaccharides and polyphenols decreased the ileal absorption of glucose and magnesium from the perfusion fluid in comparison to the F group. It was reflected in the lowest serum concentration of glucose in the FP group measured just after the perfusion period. Both preparations F and FP similarly increased the rate of calcium absorption when compared to the control treatment.
Microplastics and the functional traits of fishes: A global meta‐analysis

Over the years, concern about the effects of microplastics has grown. Here, we answered the main question “What are the impacts of microplastics on the functional traits of fish species? ” through a meta‐analysis. The general impact of microplastic exposure on the functional traits of fishes and specifically on eight variables, namely, behaviour, development, fecundity, feeding, growth, health, hatching and survival was explored. Subgroup analyses were performed to detect correlations between the impact of microplastics and the following factors: species, life stage, habitat, water column habitat, day of exposure to microplastics and microplastic size, type and shape. A meta‐regression analysis allowed understanding the correlation between the impact of microplastics and the size of organisms. Generally, microplastics have a negative effect on the functional traits of fishes. Feeding and behaviour, followed by growth showed the greatest impact. Among the subgroup analysis, four of the eight variables considered showed a significant difference between groups: species, life stage, microplastic shape and days of exposure to microplastics. Depending on their life stage, organisms may be more sensitive to microplastic pollution. Changes in growth rates, development of early life stage and behavioural patterns in fishes may have a negative effect on the structure and functions of aquatic ecosystem in the long term and consequently affect the ability of aquatic ecosystems to provide ecosystem services and sustain human communities.