Miracle-dz/UniFAR-FTUs huggingface dataset:
Divergent pathways mediate 5-HT1A receptor agonist effects on close social interaction, grooming and aggressive behaviour in mice: Exploring the involvement of the oxytocin and vasopressin systems

Background: 5-HT1A receptor (5-HT1AR) abnormalities are implicated in aggression, and there has been considerable interest in developing 5-HT1AR agonists for treating aggression. Endogenous oxytocin (OXT) released upon stimulation of 5-HT1ARs in the hypothalamus mediates at least some of the effects of 5-HT1AR agonists on social behaviour. Aims: Given 5-HT1AR, OXT receptor (OXTR) and vasopressin V1a receptor (V1aR) agonists can all reduce aggression, the current study aimed to determine whether the anti-aggressive effects of 5-HT1AR stimulation can also be explained by downstream actions at OXTRs and/or V1aRs in a mouse model of non-territorial, hyper-aggressive behaviour. Methods: Male Swiss mice (N=80) were socially isolated or group housed for six weeks prior to the start of testing. Testing involved placing two unfamiliar weight- and condition-matched mice together in a neutral context for 10 minutes. Results: Social isolation led to a pronounced increase in aggressive behaviour, which was dose-dependently inhibited by the 5-HT1AR agonist 8-OH-DPAT (0.1, 0.3 and 1 mg/kg intraperitoneally (i.p.)), with accompanying increases in close social contact (huddling) and grooming. The effects of 8-OH-DPAT on aggression, huddling and grooming were blocked by pretreatment with a selective 5-HT1AR antagonist (WAY-100635; 0.1 mg/kg i.p.). The anti-aggressive effects of 8-OH-DPAT were unaffected by an OXTR antagonist (L-368,899; 10 mg/kg i.p.), whereas the effects on huddling and grooming were inhibited. Pretreatment with a V1aR antagonist (SR49059; 20 mg/kg i.p.) had no effect. Conclusions: Our study suggests that stimulation of endogenous oxytocin is involved in the effects of 5-HT1AR activation on close social contact and grooming but not aggression.
Using volunteers to improve the experience of older patients in the emergency department.

OBJECTIVES The Maximizing Aging Using Volunteer Engagement in the Emergency Department (MAUVE + ED) program connects specially trained volunteers with older patients whose personal and social needs are not always met within the busy ED environment. The objective of this study was to describe the development and implementation of the MAUVE + ED program. METHODS Volunteers were trained to identify and approach older patients at risk for adverse outcomes, including poor patient experience, and invite such patients to participate in the program. The program is available to all patients >65 years, and those with confusion, patients who were alone, those with mobility issues, and patients with increased length of stay in the ED. Volunteers documented their activities after each patient encounter using a standardized paper-based data collection form. RESULTS Over the program's initial 6-month period, the MAUVE + ED volunteers reported a total of 896 encounters with 718 unique patients. The median time (interquartile range [IQR]) a MAUVE volunteer spent with a patient was 10 minutes (IQR = 5, 20), with a range of 1 to 130 minutes. The median number of patients seen per shift was 7 (IQR = 6, 9), with a range of 1 to 16 patients per shift. The most common activities the volunteer assisted with were therapeutic activities/social visits (n = 859; 95.9%), orientation activities (n = 501; 55.9%), and hydration assistance (n = 231; 25.8%). The least common were mobility assistance (n = 36; 4.0%), and vision/hearing assistance (n = 13; 1.5%). CONCLUSIONS Preliminary data suggest the MAUVE + ED volunteers were able to provide additional care to older adults and their families/carers in the ED.
Replication Study: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

As part of the Reproducibility Project: Cancer Biology we published a Registered Report (Khan et al., 2015), that described how we intended to replicate selected experiments from the paper "A coding-independent function of gene and pseudogene mRNAs regulates tumour biology" (Poliseno et al., 2010). Here we report the results. We found PTEN depletion in the prostate cancer cell line DU145 did not detectably impact expression of the corresponding pseudogene PTENP1. Similarly, depletion of PTENP1 did not impact PTEN mRNA levels. The original study reported PTEN or PTENP1 depletion statistically reduced the corresponding pseudogene or gene (Figure 2G; Poliseno et al., 2010). PTEN and/or PTENP1 depletion in DU145 cells decreased PTEN protein expression, which was similar to the original study (Figure 2H; Poliseno et al., 2010). Further, depletion of PTEN and/or PTENP1 increased DU145 proliferation compared to non-targeting siRNA, which was in the same direction as the original study (Figure 2F; Poliseno et al., 2010), but not statistically significant. We found PTEN 3'UTR overexpression in DU145 cells did not impact PTENP1 expression, while the original study reported PTEN 3'UTR increased PTENP1 levels (Figure 4A; Poliseno et al., 2010). Overexpression of PTEN 3'UTR also statistically decreased DU145 proliferation compared to controls, which was similar to the findings reported in the original study (Figure 4A; Poliseno et al., 2010). Differences between the original study and this replication attempt, such as level of knockdown efficiency and cellular confluence, are factors that might have influenced the results. Finally, where possible, we report meta-analyses for each result.
Primary prevention of venous thromboembolism with apixaban for multiple myeloma patients receiving immunomodulatory agents

Immunomodulatory drugs (IMiDs) have improved survival of patients with multiple myeloma (MM) and comprise the therapeutic backbone at all phases of therapy. Although well‐tolerated, IMiDs increase rates of venous thromboembolism (VTE). In this phase IV, single‐arm pilot study, fifty patients with MM on IMiDs received apixaban 2·5 mg orally twice daily for primary prevention of VTE and were prospectively monitored for six months. The primary safety outcomes were rates of major haemorrhage and clinically relevant non‐major haemorrhage over six months. The primary efficacy outcome was the rate of symptomatic VTE over six months. IMiDs used were lenalidomide (58%) or pomalidomide (42%). During the six‐month evaluation period, no patients experienced major haemorrhage or VTE. Three patients experienced clinically relevant, non‐major haemorrhage which was managed medically, and all were able to resume apixaban. One patient stopped therapy shortly after initiation due to an allergic reaction to apixaban. No patients experienced stroke, myocardial infarction, or death. In this pilot study, low‐dose apixaban was safe and well‐tolerated as a primary prevention therapy of VTE for patients with MM receiving IMiDs. Further studies are needed to validate low‐dose apixaban as a standard primary prevention anti‐thrombotic strategy for patients with MM receiving IMiDs.
Optimization of an oral mucosa in vitro model based on cell line TR146

ABSTRACT During the last years, the popularity of saliva has been increasing for its applicability as a diagnostic fluid. Blood biomarker molecules have to cross the blood-saliva barrier (BSB) in order to appear in saliva. The BSB consists of all oral and salivary gland epithelial barriers. Within this context, the optimization of in vitro models for mechanistic studies about the transport of molecules across the oral mucosa is an important task. Here, we describe the optimization and comprehensive characterization of a Transwell model of the oral mucosa based on the epithelial cell line TR146. Through systematic media optimization investigating 12 different set-ups, a significant increase of barrier integrity upon airlift cultivation was achieved for TR146 cell layers. The distinct improvement of the paracellular barrier was shown by measurements of transepithelial electrical resistance (TEER) and carboxyfluorescein permeability assays. Histological characterization supported TEER data and showed a stratified, non-keratinized multilayer of the optimized TR146 model. High-Throughput qPCR using 96 selected markers for keratinization, cornification, epithelial–mesenchymal transition, aquaporins, mucins, tight junctions, receptors, and transporter proteins was applied to comprehensively characterize the systematic optimization of the cellular model and validate against human biopsy samples. Data revealed the expression of several genes in the oral mucosa epithelium for the first time and elucidated novel regulations dependent on culture conditions. Moreover, functional activity of ABC transporters ABCB1 and ABCC4 was shown indicating the applicability of the model for drug transport studies. In conclusion, a Transwell model of the oral mucosa epithelium was optimized being suitable for transport studies.
The Titanium Angular Clip Prosthesis for Ossicular Chain Reconstruction: Long-Term Results.

OBJECTIVES To describe the long-term results of the titanium angular clip prosthesis 10 years after its initial description. STUDY DESIGN Clinical retrospective study. SETTING Tertiary referral center. PATIENTS Sixty three patients with isolated defects of the long process of the incus where the ossicular chain was reconstructed by a titanium angular clip prosthesis. INTERVENTIONS Therapeutic. MAIN OUTCOME MEASURES The mean air-bone gap was calculated over the frequencies of 0.5, 1, 2, 3, and 4 kHz. RESULTS The placement of the prosthesis was straightforward in all patients, without any complication. During the first follow-up visit after 3 weeks (n = 61) the mean air-bone gap (ABG) was reduced by 10 dB HL, and from 24 dB HL preoperatively to 14 dB HL. At the long-term follow-up appointment-4 years after implantation (n = 29)-the mean ABG was still reduced by 8 dB HL, from a mean of 26 dB HL preoperatively to 18 dB HL. CONCLUSION The use of the titanium angular clip prosthesis is a safe and reliable way to bridge an isolated erosion of the long process of the incus, leading to significant and long-lasting improvement of the ABG both in the short and long-term follow-up. A similarly large improvement of the sound transmission can be achieved both in patients with a Type A and a Type B/C tympanogram.
Preliminary validation of the Dutch version of the Posttraumatic stress disorder checklist for DSM-5 (PCL-5) after traumatic brain injury in a civilian population

The Posttraumatic stress disorder checklist (PCL) is the most widely used questionnaire to screen for symptoms of posttraumatic stress disorder (PTSD), based on the Diagnostic and Statistical manual of Mental disorders (DSM-IV) criteria. In the latest edition of the DSM (DSM-5), the criteria for PTSD were revised leading to the development of the PCL-5. So far, there is no validated Dutch version of the PCL-5. The aim of this study is to determine psychometric characteristics of the Dutch translation and linguistic validation of the PCL-5 and to evaluate internal consistency, criterion and structural validity. In a population of 495 civilian, traumatic brain injury patients, the PCL-5, the Generalized anxiety disorder questionnaire and the Depression scale of the Patient health questionnaire were administered. The PCL-5 was translated in Dutch following a strict procedure of linguistic validation and cognitive debriefing. Results show an excellent internal consistency and high criterion validity. Confirmatory factor analysis demonstrated a good fit for the four-factor DSM-5 model, but a superior fit for the six-factor Anhedonia model and the seven-factor Hybrid model, similar to the English version of the PCL-5. Preliminary validation of the Dutch translation of the PCL-5 was proven to be psychometrically sound and can be used for clinical and academic purposes, specifically for TBI patients. Future research should examine concurrent and discriminant validity for the Dutch translation in broader populations at risk for PTSD, and include a structured interview to evaluate diagnostic utility.
Characterization of BAY 1905254, an Immune Checkpoint Inhibitor Targeting the Immunoglobulin-Like Domain Containing Receptor 2 (ILDR2)

ILDR2 is an immune checkpoint expressed by certain stromal lymph node cells called fibroblastic reticular cells. ILDR2 negatively interferes with T-cell activity, and its inhibition by the antibody BAY 1905254 is beneficial in preclinical models. The immunoglobulin-like domain containing receptor 2 (ILDR2), a type I transmembrane protein belonging to the B7 family of immunomodulatory receptors, has been described to induce an immunosuppressive effect on T-cell responses. Besides its expression in several nonlymphoid tissue types, we found that ILDR2 was also expressed in fibroblastic reticular cells (FRC) in the stromal part of the lymph node. These immunoregulatory cells were located in the T-cell zone and were essential for the recruitment of naïve T cells and activated dendritic cells to the lymph nodes. Previously, it has been shown that an ILDR2-Fc fusion protein exhibits immunomodulatory effects in several models of autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and type I diabetes. Herein, we report the generation and characterization of a human/mouse/monkey cross-reactive anti-ILDR2 hIgG2 antibody, BAY 1905254, developed to block the immunosuppressive activity of ILDR2 for cancer immunotherapy. BAY 1905254 was shown to promote T-cell activation in vitro and enhance antigen-specific T-cell proliferation and cytotoxicity in vivo in mice. BAY 1905254 also showed potent efficacy in various syngeneic mouse cancer models, and the efficacy was found to correlate with increasing mutational load in the cancer models used. Additive or even synergistic antitumor effects were observed when BAY 1905254 was administered in combination with anti–PD-L1, an immunogenic cell death–inducing chemotherapeutic, or with tumor antigen immunization. Taken together, our data showed that BAY 1905254 is a potential drug candidate for cancer immunotherapy, supporting its further evaluation.
Implicit Bias in Pediatrics: An Emerging Focus in Health Equity Research

* Abbreviation: ED — : emergency department Despite large-scale investments in research, health policy, care delivery models, and medical school curricula, inequities along the continuum of child health care and health persist.1,2 The study “Racial and Ethnic Differences in Emergency Department Pain Management of Children with Fractures”3 in this issue of Pediatrics contributes new insights into the field of pediatric health equity research with a focus on pain in the emergency department (ED) setting. Goyal et al3 find that although racial and/or ethnic minority children were more likely to receive analgesics and achieve a ≥2-point reduction in pain, they were less likely to receive opioids and experience optimal pain reduction. This work builds on a well-established body of literature in adult care and an emerging evidence base in pediatrics demonstrating inequities in analgesic administration.4 Studies in pediatric EDs have demonstrated racial and/or ethnic disparities in analgesic management for children presenting with acute abdominal pain and appendicitis.5,6 The current study adds to the field by combining process and outcome measures in assessing analgesic management. As the authors and other researchers in the field have highlighted, there … Address correspondence to Jean L. Raphael, MD, MPH, Texas Children’s Hospital, 6701 Fannin St, Suite D.1540. 00, Houston, TX 77030. E-mail: raphael{at}bcm.edu
Phigaro: high-throughput prophage sequence annotation

SUMMARY Phigaro is a standalone command-line application that is able to detect prophage regions taking raw genome and metagenome assemblies as an input. It also produces dynamic annotated "prophage genome maps" and marks possible transposon insertion spots inside prophages. It is applicable for mining prophage regions from large metagenomic datasets. AVAILABILITY Source code for Phigaro is freely available for download at https://github.com/bobeobibo/phigaro along with test data. The code is written in Python. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Dealing with highly skewed hospital length of stay distributions: The use of Gamma mixture models to study delivery hospitalizations

The increased focus on addressing severe maternal morbidity and maternal mortality has led to studies investigating patient and hospital characteristics associated with longer hospital stays. Length of stay (LOS) for delivery hospitalizations has a strongly skewed distribution with the vast majority of LOS lasting two to three days in the United States. Prior studies typically focused on common LOSs and dealt with the long LOS distribution tail in ways to fit conventional statistical analyses (e.g., log transformation, trimming). This study demonstrates the use of Gamma mixture models to analyze the skewed LOS distribution. Gamma mixture models are flexible and, do not require data transformation or removal of outliers to accommodate many outcome distribution shapes, these models allow for the analysis of patients staying in the hospital for a longer time, which often includes those women experiencing worse outcomes. Random effects are included in the model to account for patients being treated within the same hospitals. Further, the role and influence of differing placements of covariates on the results is discussed in the context of distinct model specifications of the Gamma mixture regression model. The application of these models shows that they are robust to the placement of covariates and random effects. Using New York State data, the models showed that longer LOS for childbirth hospitalizations were more common in hospitals designated to accept more complicated deliveries, across hospital types, and among Black women. Primary insurance also was associated with LOS. Substantial variation between hospitals suggests the need to investigate protocols to standardize evidence-based medical care.
From conservation to structure, studies of magnetosome associated cation diffusion facilitators (CDF) proteins in Proteobacteria

Magnetotactic bacteria (MTB) are prokaryotes that sense the geomagnetic field lines to geolocate and navigate in aquatic sediments. They are polyphyletically distributed in several bacterial divisions but are mainly represented in the Proteobacteria. In this phylum, magnetotactic Deltaproteobacteria represent the most ancestral class of MTB. Like all MTB, they synthesize membrane-enclosed magnetic nanoparticles, called magnetosomes, for magnetic sensing. Magnetosome biogenesis is a complex process involving a specific set of genes that are conserved across MTB. Two of the most conserved genes are mamB and mamM, that encode for the magnetosome-associated proteins and are homologous to the cation diffusion facilitator (CDF) protein family. In magnetotactic Alphaproteobacteria MTB species, MamB and MamM proteins have been well characterized and play a central role in iron-transport required for biomineralization. However, their structural conservation and their role in more ancestral groups of MTB like the Deltaproteobacteria have not been established. Here we studied magnetite cluster MamB and MamM cytosolic C-terminal domain (CTD) structures from a phylogenetically distant magnetotactic Deltaproteobacteria species represented by BW-1 strain, which has the unique ability to biomineralize magnetite and greigite. We characterized them in solution, analyzed their crystal structures and compared them to those characterized in Alphaproteobacteria MTB species. We showed that despite the high phylogenetic distance, MamBBW-1 and MamMBW-1 CTDs share high structural similarity with known CDF-CTDs and will probably share a common function with the Alphaproteobacteria MamB and MamM.
Unprecedented Quassinoids from Eurycoma longifolia: Biogenetic Evidence and Antifeedant Effects.

Six new quassinoids (1-6) were isolated from the roots of Eurycoma longifolia, and their structures with absolute configurations were determined unambiguously by spectroscopic analyses and single-crystal X-ray crystallographic experiments. Compounds 1 and 2 are the first members of a new class of quassinoids with an unusual C26 carbon skeleton. Compound 6 features a C20 cage-like scaffold with an unprecedented densely functionalized 2,5-dioxatricyclo[5.2. 2.04,8]undecane core. The discovery of the two C26 quassinoids 1 and 2 has provided firm evidence for the better understanding the biogenetic process from C30 triterpenoid precursors to quassinoids. Compound 5 exhibited significant antifeedant activity on the diamondback moth (DBM) larvae and excellent systemic absorption and accumulated properties in Brassica chinensis.
“Take Me To Your Leader”: An Electrophysiological Appraisal of the Role of Hub Cells in Pancreatic Islets

The coordinated electrical activity of β-cells within the pancreatic islet drives oscillatory insulin secretion. A recent hypothesis postulates that specially equipped “hub” or “leader” cells within the β-cell network drive islet oscillations and that electrically silencing or optically ablating these cells suppresses coordinated electrical activity (and thus insulin secretion) in the rest of the islet. In this Perspective, we discuss this hypothesis in relation to established principles of electrophysiological theory. We conclude that whereas electrical coupling between β-cells is sufficient for the propagation of excitation across the islet, there is no obvious electrophysiological mechanism that explains how hyperpolarizing a hub cell results in widespread inhibition of islet electrical activity and disruption of their coordination. Thus, intraislet diffusible factors should perhaps be considered as an alternate mechanism.
Independent contributions of social cognition and depression to functional status after moderate or severe traumatic brain injury

ABSTRACT Impairments in cognitive processing related to social understanding and communication (i.e., “social cognition”) are well documented after moderate or severe traumatic brain injury (TBI) and can contribute to negative functional outcome. Depression is also a common feature of TBI with detrimental functional consequences. We evaluated relationships between social cognition, depression symptom severity, and functional status in individuals with chronic TBI (>1 year post injury; n = 25) and healthy controls (n = 30) using objective tests of social cognition as well as self-reported depression (Beck Depression Inventory-II) and functional status (Functional Behavior Profile). Results revealed significant relationships between depression and functional status across the sample, and relationships between social cognition and functional status specific to TBI. In the TBI group only, social cognition significantly predicted both overall and social functional status above and beyond depression. Group differences in functional status were independently mediated by social cognition and, especially, depression. Our findings suggest that social cognitive impairments and depression are distinct, functionally relevant TBI sequelae. Interventions to improve social functioning in this population may be most effective when contextualized within treatments for emotional disturbances.