Miracle-dz/UniFAR-FTUs huggingface dataset:
Are there sex differences in fetal growth strategies and in the long-term effects of pregnancy complications on cognitive functioning?

Abstract Males and females have been proposed to have different prenatal growth strategies, whereby males invest more in fetal growth and less in placental development, leaving them more susceptible to early-life adversity. We tested predictions of this hypothesis using data from the National Collaborative Perinatal Project. Male newborns were heavier than females, but there was no difference in placental weight, adjusting for birthweight. Among infants born prior to 33 weeks, the difference in birthweight between males and females was greater among those who did not survive than among those who did, potentially reflecting a strategy whereby males maintained growth in the face of prenatal insults, while females adjusted growth. However, there was no significant difference in mortality between the sexes. Being born small-for-gestational age or very preterm (prior to 33 weeks) was associated with significantly reduced performance for most of the cognitive traits examined at 7 years, although maternal preeclampsia was associated with reduced performance in fewer traits. Generally, these effects of early-life adversity (poor fetal growth, prematurity, and preeclampsia) did not differ between the sexes. However, analyzing the sexes separately (rather than testing the interaction between sex and adversity) resulted in numerous spurious sex-specific effects, whereby the effect of early-life adversity appeared to be significant in one sex but not the other. Overall, we found little support for the hypothesis that males prioritize growth more than females, and that this makes them more susceptible to early-life adversity. Furthermore, our results show that analyzing the sexes separately, rather than testing the adversity by sex interaction, can be highly misleading.
Major Role for Cellular MicroRNAs, Long Noncoding RNAs (lncRNAs), and the Epstein-Barr Virus-Encoded BART lncRNA during Tumor Growth In Vivo

This study identified the total effects of EBV and a viral long noncoding RNA (BART lncRNA) on cellular RNA expression when grown as cells in culture and when grown as tumors in immunodeficient mice. The effects on cellular mRNA expression, lncRNA expression, and cellular and viral miR expression were determined using next-generation sequencing (NGS) and bioinformatics functional analysis. ABSTRACT This study assessed the effects of Epstein-Barr virus (EBV) and one form of virally encoded BART long noncoding RNAs (lncRNAs) on cellular expression in epithelial cells grown in vitro and as tumors in vivo determined by high-throughput RNA sequencing of mRNA and small RNAs. Hierarchical clustering based on gene expression distinguished the cell lines from the tumors and distinguished the EBV-positive tumors and the BART tumors from the EBV-negative tumors. EBV and BART expression also induced specific expression changes in cellular microRNAs (miRs) and lncRNAs. Multiple known and predicted targets of the viral miRs, the induced cellular miRs, and lncRNAs were identified in the altered gene set. The changes in expression in vivo indicated that the suppression of growth pathways in vivo reflects increased expression of cellular miRs in all tumors. In the EBV and BART tumors, many of the targets of the induced miRs were not changed and the seed sequences of the nonfunctional miRs were found to have homologous regions within the BART lncRNA. The inhibition of these miR effects on known targets suggests that these induced miRs have reduced function due to sponging by the BART lncRNA. This composite analysis identified the effects of EBV on cellular miRs and lncRNAs with a functional readout through identification of the simultaneous effects on gene expression. Major shifts in gene expression in vivo are likely mediated by effects on cellular noncoding RNAs. Additionally, a predicted property of the BART lncRNA is to functionally inhibit the induced cellular miRs. IMPORTANCE This study identified the total effects of EBV and a viral long noncoding RNA (BART lncRNA) on cellular RNA expression when grown as cells in culture and when grown as tumors in immunodeficient mice. The effects on cellular mRNA expression, lncRNA expression, and cellular and viral miR expression were determined using next-generation sequencing (NGS) and bioinformatics functional analysis. Many cellular growth pathways that are activated during growth in culture are decreased during growth as tumors. This study shows that these changes in expression are accompanied by induction of cellular-growth-inhibitory miRs. However, in the EBV tumors and in tumors expressing the BART lncRNA, many of the known targets of the inhibitory miRs are not affected. Regions of strong homology to the seed sequences of these miRs were identified in the BART lncRNA. These findings suggest that the BART lncRNA functions as a sponge for growth-inhibitory miRs.
The Role of Food in the Treatment of Bowel Disorders: Focus on Irritable Bowel Syndrome and Functional Constipation

Irritable bowel syndrome (IBS) and functional constipation (FC) are among the most common disorders of gut–brain interaction, affecting millions of individuals worldwide. Most patients with disorders of gut–brain interaction perceive food as a trigger for their gastrointestinal symptoms, and specific dietary manipulations/advice have now been recognized as a cornerstone therapeutic option for IBS and FC. We discuss in detail the 2 most common dietary interventions used for the management of IBS-general dietary advice based on the National Institute for Health and Care Excellence guidelines and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). We summarize the literature around the possible mechanisms of FODMAP-mediated IBS pathophysiology, the current 3-step, top-down approach of administering a low FODMAP diet (LFD) (restriction phase, followed by reintroduction and personalization), the efficacy data of its restriction and personalization phases, and possible biomarkers for response to an LFD. We also summarize the limitations and challenges of an LFD along with the alternative approach to administering an LFD (e.g., bottom-up). Finally, we discuss the available efficacy data for fiber, other dietary interventions (e.g., Mediterranean diet, gluten-free diet, and holistic dietary interventions), and functional foods (e.g., kiwifruit, rhubarb, aloe, and prunes) in the management of IBS and FC.
Plant lipid phosphate phosphatases: current advances and future outlooks

Abstract Lipids are widely distributed in various tissues of an organism, mainly in plant storage organs (e.g., fruits, seeds, etc.). Lipids are vital biological substances that are involved in: signal transduction, membrane biogenesis, energy storage, and the formation of transmembrane fat-soluble substances. Some lipids and related lipid derivatives could be changed in their: content, location, or physiological activity by the external environment, such as biotic or abiotic stresses. Lipid phosphate phosphatases (LPPs) play important roles in regulating intermediary lipid metabolism and cellular signal response. LPPs can dephosphorylate lipid phosphates containing phosphate monolipid bonds such as: phosphatidic acid, lysophosphatidic acid (LPA), and diacylglycerol pyrophosphate, etc. These processes can change the contents of some important lipid signal mediation such as diacylglycerol and LPA, affecting lipid signal transmission. Here, we summarize the research progress of LPPs in plants, emphasizing the structural and biochemical characteristics of LPPs and their role in spatio-temporal regulation. In the future, more in-depth studies are required to boost our understanding of the key role of plant LPPs and lipid metabolism in: signal regulation, stress tolerance pathway, and plant growth and development.
Class C β-Lactamases: Molecular Characteristics

Class C β-lactamases or cephalosporinases can be classified into two functional groups (1, 1e) with considerable molecular variability (≤20% sequence identity). These enzymes are mostly encoded by chromosomal and inducible genes and are widespread among bacteria, including Proteobacteria in particular. SUMMARY Class C β-lactamases or cephalosporinases can be classified into two functional groups (1, 1e) with considerable molecular variability (≤20% sequence identity). These enzymes are mostly encoded by chromosomal and inducible genes and are widespread among bacteria, including Proteobacteria in particular. Molecular identification is based principally on three catalytic motifs (64SXSK, 150YXN, 315KTG), but more than 70 conserved amino-acid residues (≥90%) have been identified, many close to these catalytic motifs. Nevertheless, the identification of a tiny, phylogenetically distant cluster (including enzymes from the genera Legionella, Bradyrhizobium, and Parachlamydia) has raised questions about the possible existence of a C2 subclass of β-lactamases, previously identified as serine hydrolases. In a context of the clinical emergence of extended-spectrum AmpC β-lactamases (ESACs), the genetic modifications observed in vivo and in vitro (point mutations, insertions, or deletions) during the evolution of these enzymes have mostly involved the Ω- and H-10/R2-loops, which vary considerably between genera, and, in some cases, the conserved triplet 150YXN. Furthermore, the conserved deletion of several amino-acid residues in opportunistic pathogenic species of Acinetobacter, such as A. baumannii, A. calcoaceticus, A. pittii and A. nosocomialis (deletion of residues 304–306), and in Hafnia alvei and H. paralvei (deletion of residues 289–290), provides support for the notion of natural ESACs. The emergence of higher levels of resistance to β-lactams, including carbapenems, and to inhibitors such as avibactam is a reality, as the enzymes responsible are subject to complex regulation encompassing several other genes (ampR, ampD, ampG, etc.). Combinations of resistance mechanisms may therefore be at work, including overproduction or change in permeability, with the loss of porins and/or activation of efflux systems.
Preeclampsia and Fetal Congenital Heart Defects

Endothelial dysfunction, impaired implantation and placental insufficiency have been identified as mechanisms behind the development of pre-eclampsia, resulting in angiogenic factors’ alteration. Angiogenic imbalance is also associated with congenital heart defects, and this common physiologic pathway may explain the association between them and pre-eclampsia. This review aims to understand the physiology shared by these two entities and whether women with pre-eclampsia have an increased risk of fetal congenital heart defects (or the opposite). The present research has highlighted multiple vasculogenic pathways associated with heart defects and pre-eclampsia, but also epigenetic and environmental factors, contributing both. It is also known that fetuses with a prenatal diagnosis of congenital heart disease have an increased risk of several comorbidities, including intrauterine growth restriction. Moreover, the impact of pre-eclampsia goes beyond pregnancy as it increases the risk for following pregnancies and for diseases later in life in both offspring and mothers. Given the morbidity and mortality associated with these conditions, it is of foremost importance to understand how they are related and its causative mechanisms. This knowledge may allow earlier diagnosis, an adequate surveillance or even the implementation of preventive strategies.
Association of surveillance technology and staff opinions with physical restraint use in nursing homes: Cross‐sectional study

Physical restraints are used in nursing homes (NHs) despite their negative consequences. Use of surveillance technologies as alternatives to physical forms of restraints and negative staff opinions about the appropriateness of restraint use have been postulated to reduce this practice; however, these have rarely been investigated alongside resident outcome data. This study aimed to measure physical restraint prevalence in Swiss NHs and its associations with (a) the use of surveillance technologies and (b) staff's opinion about the appropriateness of physical restraint use.
Personality disorders and forensic assessments: The benefits of ICD-11

A recent landmark case in the Australian state of Victoria clariﬁed the ways in which personality disorders may be taken into account when the courts are sentencing convicted offenders. The ruling especially emphasised: the need for evidence to be ‘cogent’; the need to determine ‘severity’ of the personality disorder; the need to consider whether there is a ‘connection to the offending’; the need for caution when diagnoses are based solely on behaviour; and the need to consider rehabilitative prospects and community protection. The ruling has significant implications for how forensic experts in all jurisdictions might most effectively assist the courts with the task of sentencing offenders with personality disorders. In this paper we argue that the approach to diagnosis taken in the newly published ICD-11 manual, that eschews ‘categories’ of personality disorder, in favour of a dimensional model supported by trait theory, is of much greater utility to forensic mental health experts striving to address these issues, compared to traditional ‘categorical’ approaches.
2D Transition Metal Dichalcogenides Trigger Trained Immunity in Human Macrophages through Epigenetic and Metabolic Pathways.

Trained immunity is a recently described phenomenon whereby cells of the innate immune system undergo long-term epigenetic and/or metabolic reprogramming following a short-term interaction with microbes or microbial products. Here, it is shown that 2D transition metal dichalcogenides (TMDs) trigger trained immunity in primary human monocyte-derived macrophages. First, aqueous dispersions of 2D crystal formulations of MoS2 and WS2 are tested, and no cytotoxicity is found despite avid uptake of these materials by macrophages. However, when macrophages are pre-exposed to TMDs, followed by a resting period, this causes a marked modulation of immune-specific gene expression upon subsequent challenge with a microbial agent (i.e., bacterial lipopolysaccharides). Specifically, MoS2 triggers trained immunity through an epigenetic pathway insofar as the histone methyltransferase inhibitor methylthioadenosine reverses these effects. Furthermore, MoS2 triggers an elevation of cyclic adenosine monophosphate (cAMP) levels in macrophages and increased glycolysis is also evidenced in cells subjected to MoS2 training, pointing toward a metabolic rewiring of the cells. Importantly, it is observed that MoS2 triggers the upregulation of Mo-dependent enzymes in macrophages, thus confirming that Mo is bioavailable in these cells. In conclusion, MoS2 is identified as a novel inducer of trained immunity. Thus, TMDs could potentially be harnessed as immunomodulatory agents.
Elevated Levels of Three Reactive Oxygen Species and Fe(II) in the Antibiotic-Surviving Population of Mycobacteria Facilitate De Novo Emergence of Genetic Resisters to Antibiotics

We had earlier reported the de novo emergence of genetic resisters of Mycobacterium tuberculosis and Mycobacterium smegmatis to rifampicin and moxifloxacin from the antibiotic-surviving population containing elevated levels of the non-DNA-specific mutagenic reactive oxygen species (ROS) hydroxyl radical. Since hydroxyl radical is generated by Fenton reaction between Fe(II) and H2O2, which is produced by superoxide dismutation, we here report significantly elevated levels of these three ROS and Fe(II) in the M. smegmatis rifampicin-surviving population. ABSTRACT We had earlier reported the de novo emergence of genetic resisters of Mycobacterium tuberculosis and Mycobacterium smegmatis to rifampicin and moxifloxacin from the antibiotic-surviving population containing elevated levels of the non-DNA-specific mutagenic reactive oxygen species (ROS) hydroxyl radical. Since hydroxyl radical is generated by Fenton reaction between Fe(II) and H2O2, which is produced by superoxide dismutation, we here report significantly elevated levels of these three ROS and Fe(II) in the M. smegmatis rifampicin-surviving population. Elevated levels of superoxide and the consequential formation of high levels of H2O2 and Fe(II) led to the generation of hydroxyl radical, facilitating de novo high frequency emergence of antibiotic resisters. The M. smegmatis cultures, exposed to nontoxic concentrations of the ROS scavenger, thiourea (TU), and the NADH oxidase (one of the superoxide producers) inhibitor, diphenyleneiodonium chloride (DPI), showed a reduction in the levels of the three ROS, Fe(II), and antibiotic resister generation frequency. The non-antibiotic-exposed cultures grown in the absence/presence of TU/DPI did not show increased ROS, Fe(II) levels, or antibiotic resister generation frequency. The antibiotic-surviving population showed significantly increased expression and activity of superoxide-producing genes and decreased expression of antioxidant and DNA repair genes, revealing an environment conducive for the acquisition and retention of mutations. Since we recently reported significant comparability between the antibiotic-survival gene expression profiles of the saprophyte-cum-opportunistic pathogens M. smegmatis and the M. tuberculosis in tuberculosis patients undergoing treatment, we discuss the clinical relevance of the findings on the mechanism of emergence of antibiotic-resistant mycobacterial strains.
Can a small number of pedestrian impact scenarios represent the range of real-world pedestrian injuries?

The purpose of this study is to evaluate the predictive capability of a virtual test system (VTS) proposed for vehicle front assessment of pedestrian injury risk. The VTS accounts for a broad range of impact scenarios in pedestrian accidents and the assessment is done using recent pedestrian accident data. Firstly, simulation test samples (STS) accounting for the broad range of vehicle impact speed pedestrian height and gait stance in real world impact scenarios were developed based on different sets of multibody vehicle-to-pedestrian impact simulations. Then a sedan and a van model were tested using the defined STSs. The AIS2+ injuries predicted from these STSs for each vehicle model were weighted by the involving proportion of each impact scenario observed from German In-Depth Accident Study (GIDAS) pedestrian accident data via a defined Injury Weighting System (IWS). The injury predictive capability of the VTSs using different STS sample sizes and the corresponding IWS was evaluated by comparing the predicted AIS 2+ injury rate and distribution of AIS 2+ injuries as a function of pedestrian body region and height, vehicle class and impact speed with that observed from the GIDAS data. The results indicate that the proposed VTS using a STS of about 120 cases is broadly capable of predicting the AIS 2+ injury rate and distribution of pedestrian AIS 2+ injuries observed from the real-world accidents when the same vehicle class distribution as the accident data is employed. The VTS can be considered as an effective approach for assessing pedestrian safety performance of vehicle front designs at the generalised level.
The Significance of Tumor Budding and Immunohistochemical Axl Expression in Gallbladder Adenocarcinomas

Background: Tumor budding is a histopathological finding that is accepted as an indicator of epithelial-mesenchymal transformation in many solid tumors. Axl is a Receptor Tyrosine Kinase (RTK) family member and contributes to epithelial-mesenchymal transformation. It has been reported that its overexpression in various solid cancer cells is associated with a poor prognosis. It is claimed that Axl RTK may be the targeted molecule in treating some cancers due to its location in the cell membrane. Aims: To investigate the relationship between immunohistochemical (IHC) Axl expression with tumor budding on the histopathological level and their prognostic significance in patients with gallbladder carcinoma. Thus, it is aimed to contribute to the emergence of a molecular option for targeted, personalized therapy in these patients. Study Design: A retrospective cross-sectional study. Methods: Thirty-eight gallbladder cancer patients who underwent surgery between 2000 and 2017 were included in the study. The expressions of Axl RTK in tumor tissues were evaluated by the IHC method. Demographic data (age, sex) of patients, histopathological features (size, growth pattern), tumor differentiation, pathological T staging, lymphovascular invasion, perineural and serosal invasion, surgical margin, tumor infiltrated lymphocyte, and tumor budding were examined. The tumor budding of the tumor was made according to the International Tumor Budding Consensus Conference and was classified as low (0-4 buds), intermediate (5-9 buds), high (≥ 10 buds). The relationship between clinical pathologic features, the survival rate, and Axl expression was analyzed with Person’s chi-square, Cox regression tests, and the Kaplan-Meier method. Results: Tumor budding was determined as low in 12, intermediate in 10, and high in 16 cases. The increased degree of tumor budding was associated with focal-diffuse Axl expression (p = 0.018), infiltrative growth patterns (p = 0.031), poor differentiation (p = 0.006), advanced pathological stage (p = 0.002), and serosal (p = 0.040), perineural (p = 0.008), and lymphovascular invasion (p < 0.0001). Overall survival time was shorter in patients with intermediate to high tumor budding compared with those with low tumor budding (p = 0.011). Conclusion: Axl expression appears to be associated with tumor budding capacity, which may be a poor prognostic criterion for patients with gallbladder cancer. It may be a good target to prevent tumor budding to reduce tumor invasion and metastasis.
Interaction between people with dysarthria and speech recognition systems: A review

ABSTRACT In recent years, rapid advancements have taken place for automatic speech recognition (ASR) systems and devices. Though ASR technologies have increased, the accessibility of these novel interaction systems is underreported and may present difficulties for people with speech impediments. In this article, we attempt to identify gaps in current research on the interaction between people with dysarthria and ASR systems and devices. We cover the period from 2011, when Siri (the first and the leading commercial voice assistant) was launched, to 2020. The review employs an interaction framework in which each element (user, input, system, and output) contributes to the interaction process. To select the articles for review, we conducted a search of scientific databases and academic journals. A total of 36 studies met the inclusion criteria, which included use of the word error rate (WER) as a measurement for evaluating ASR systems. This review determines that challenges in interacting with ASR systems persist even in light of the most recent commercial technologies. Further, understanding of the entire interaction process remains limited; thus, to improve this interaction, the recent progress of ASR systems must be elucidated.
Corticosteroid response predicts bronchopulmonary dysplasia status at 36 weeks in preterm infants treated with dexamethasone: A pilot study

A major barrier to therapeutic development in neonates is a lack of standardized drug response measures that can be used as clinical trial endpoints. The ability to quantify treatment response in a way that aligns with relevant downstream outcomes may be useful as a surrogate marker for new therapies, such as those for bronchopulmonary dysplasia (BPD).