Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids.

Developing time-sustained drug delivery systems is a main goal in innovative medicines. Inspired by the architecture of secretory granules from the mammalian endocrine system it has generated non-toxic microscale amyloid materials through the coordination between divalent metals and poly-histidine stretches. Like their natural counterparts that keep the functionalities of the assembled protein, those synthetic structures release biologically active proteins during a slow self-disintegration process occurring in vitro and upon in vivo administration.

Prison as a driver of recent transmissions of multidrug-resistant tuberculosis in Callao, Peru: a cross-sectional study.

Background: We sought to identify resistance patterns and key drivers of recent multidrug-resistant tuberculosis (MDR-TB) transmission in a TB-prevalent area in Peru.

Methods: Cross-sectional study including MDR complex (Mtbc) strains identified in Callao-Peru between April 2017 and February 2019. Mtbc DNA was extracted for whole genome sequencing which was used for phylogenetic inference, clustering, and resistance mutation analyses.

Resource competition predicts assembly of gut bacterial communities in vitro.

Microbial community dynamics arise through interspecies interactions, including resource competition, cross-feeding and pH modulation. The individual contributions of these mechanisms to community structure are challenging to untangle. Here we develop a framework to estimate multispecies niche overlaps by combining metabolomics data of individual species, growth measurements in spent media and mathematical models.

Phase 1 Study of Bortezomib, Fludarabine, and Melphalan, With or Without Total Marrow Irradiation, as Allogeneic Hematopoietic Stem Cell Transplant Conditioning for High-risk or Relapsed/Refractory Multiple Myeloma.

Objective: We conducted a phase 1 study of a conditioning regimen with or without total marrow irradiation (TMI) before allogeneic hematopoietic stem cell transplantation for patients with high-risk or refractory multiple myeloma.

Methods: Eighteen patients were enrolled on one of 2 strata. Patients with no prior radiation received TMI (900 cGy), fludarabine (FLU), and melphalan (MEL) conditioning, with bortezomib added in the second cohort (stratum I).

Arrestin-centred interactions at the membrane and their conformational determinants.

More than 30 years after their discovery, arrestins are recognised multiprotein scaffolds that play essential roles in G protein-coupled receptor (GPCR) regulation and signalling. Originally named for their capacity to hinder GPCR coupling to G proteins and facilitate receptor desensitisation, arrestins have emerged as key hubs for a myriad of other functions, including receptor internalisation and scaffolding of signalling complexes. Recent structural studies have started to provide snapshots of the complexes formed by GPCRs and arrestins, supporting a wealth of biochemical data delineating the molecular determinants of such interactions.

Total shoulder arthroplasty in patients with factor V Leiden.

Background: Anatomic and reverse total shoulder arthroplasty (TSA) are effective treatment options for end-stage glenohumeral osteoarthritis. However, consideration for pre-existing conditions must be taken into account. Factor V Leiden (FVL), the most common inherited thrombophilia, is one such condition that predisposes to a prothrombotic state and may affect perioperative and longer-term outcomes following TSA.

A comprehensive Exdia TRF-LFIA for simultaneous quantification of GFAP and NT-proBNP in distinguishing ischemic and hemorrhagic stroke.

The goal of this study is to create a highly sensitive time-resolved fluorescence lateral flow immunoassay (TRF-LFIA) capable of concurrently measuring glial fibrillary acidic protein (GFAP) and the N-terminal fragment of B-type natriuretic peptide precursor (NT-proBNP). This assay is designed as a diagnostic tool and aims to provide an algorithm for stroke management, specifically for distinguishing between Ischemic stroke (IS) and Hemorrhagic stroke (HS). However, LFIA to quantify simultaneous serum NT-proBNP and GFAP are not yet available.

Multifractal Analysis of Brain Tumor Interface in Glioblastoma.

The dynamics of tumor growth is a very complex process, generally accompanied by numerous chromosomal aberrations that determine its genetic and dynamical heterogeneity. Consequently, the tumor interface exhibits a non-regular and heterogeneous behavior often described by a single fractal dimension. A more suitable approach is to consider the tumor interface as a multifractal object that can be described by a set of generalized fractal dimensions.

Endocrinopathies in a Pediatric Patient Post-anatomical Hemispherectomy for Rasmussen's Encephalitis Treatment: A Case Report.

Hemispherectomy is a neurosurgical procedure that is frequently performed in pediatric patients diagnosed with Rasmussen's encephalitis. Postoperative complications include immediate complications such as hydrocephalus and hemorrhage and behavioral complications such as language impairments and contralateral weakness. However, there are limited studies or case reports that address the potential endocrinopathies associated with this and other pediatric epileptic surgeries.

PTEN loss in glioma cell lines leads to increased extracellular vesicles biogenesis and PD-L1 cargo in a PI3K-dependent manner.

Phosphatase and Tensin Homologue (PTEN) is one of the most frequently lost tumor suppressors in cancer and the predominant negative regulator of the PI3K/AKT signaling axis. A growing body of evidence has highlighted the loss of PTEN with immuno-modulatory functions including the upregulation of the programmed death ligand-1 (PD-L1), an altered tumor derived secretome that drives an immunosuppressive tumor immune microenvironment (TIME), and resistance to certain immunotherapies. Given their roles in immunosuppression and tumor growth, we examined whether the loss of PTEN would impact the biogenesis, cargo, and function of extracellular vesicles (EVs) in the context of the anti-tumor associated cytokine interferon-γ (IFN-γ).

Outcomes Following Total Hip Arthroplasty in Patients Who Have Von Willebrand Disease Depend on Postoperative Anticoagulation.

Background: Von Willebrand disease (VWD) is the most common congenital bleeding disorder. This autosomal dominant condition arises from quantitative or qualitative defects of Von Willebrand factor. To our knowledge, this study leveraged a national database to characterize the largest VWD cohort of total hip arthroplasty (THA) patients to date, assessing 90-day postoperative adverse events and 5-year revision-free survival.

Search for New Phenomena in Two-Body Invariant Mass Distributions Using Unsupervised Machine Learning for Anomaly Detection at sqrt[s]=13 TeV with the ATLAS Detector.

Searches for new resonances are performed using an unsupervised anomaly-detection technique. Events with at least one electron or muon are selected from 140  fb^{-1} of pp collisions at sqrt[s]=13  TeV recorded by ATLAS at the Large Hadron Collider. The approach involves training an autoencoder on data, and subsequently defining anomalous regions based on the reconstruction loss of the decoder.

Pseudo-Ludwig's Angina: Spontaneous Sublingual Haematoma Elicited by Warfarin.

Unlabelled: Spontaneous bleeding into the upper airways is a rare and potentially life-threatening complication of chronic anticoagulation. There are scarce cases in the literature demonstrating upper airway haematomas secondary to warfarin use, which is the predominant anticoagulant used by clinicians despite having a complex pharmacokinetic and pharmacodynamic profile. We report a compelling case featuring warfarin-induced sublingual haematoma, managed conservatively through the reversal of anticoagulation using fresh frozen plasma complemented by vigilant monitoring within the Intensive Care Unit (ICU).

Promoting equitable and patient-centred care: an analysis of patient satisfaction in urban, rural and remote primary care sites in the Philippines.

Objectives: This study measured changes in patient satisfaction levels before and after the introduction of primary care system strengthening interventions in urban, rural, and remote sites in the Philippines.

Methods: A previously validated 16-item questionnaire was distributed to 200 patients per site before implementation of interventions and to a different set of 200 patients 1 year after implementation. We compared the percentage change in highly satisfied patients per site before and after implementing interventions using a two-proportion Z-test.

Coxsackievirus infection induces direct pancreatic β cell killing but poor antiviral CD8 T cell responses.

Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β cell autoimmunity and type 1 diabetes. We investigated how CVB affects human β cells and anti-CVB T cell responses. β cells were efficiently infected by CVB in vitro, down-regulated human leukocyte antigen (HLA) class I, and presented few, selected HLA-bound viral peptides.

A novel approach to study multi-domain motions in JAK1's activation mechanism based on energy landscape.

The family of Janus Kinases (JAKs) associated with the JAK-signal transducers and activators of transcription signaling pathway plays a vital role in the regulation of various cellular processes. The conformational change of JAKs is the fundamental steps for activation, affecting multiple intracellular signaling pathways. However, the transitional process from inactive to active kinase is still a mystery.

Yield prediction in a peanut breeding program using remote sensing data and machine learning algorithms.

Peanut is a critical food crop worldwide, and the development of high-throughput phenotyping techniques is essential for enhancing the crop's genetic gain rate. Given the obvious challenges of directly estimating peanut yields through remote sensing, an approach that utilizes above-ground phenotypes to estimate underground yield is necessary. To that end, this study leveraged unmanned aerial vehicles (UAVs) for high-throughput phenotyping of surface traits in peanut.

Femoral Head Core Decompressions: Characterization of Subsequent Conversion to Total Hip Arthroplasty and Related Complications.

Background: Core decompression is a minimally invasive joint-preserving approach for early-stage osteonecrosis. The rate at which core decompression patients require total hip arthroplasty (THA) and rates of perioperative adverse outcomes have not been well-characterized.

Methods: Adult patients undergoing core decompression and/or THA with osteonecrosis of the femoral head were identified from the 2015 to 2021 Q3 PearlDiver M157 database.

Psychometric Evaluation and Validation of the HIV Stigma Scale in Spanish among Men who have Sex with Men and Transgender Women.

Stigma and discrimination toward the LGBTQ community is pervasive and negatively impacts health. Validated measures of stigma in Spanish, however, are limited and none have specifically validated HIV-related stigma in Spanish-speaking men who have sex with men (MSM) and transgender women (TGW) in resource-limited settings. The aim of this study is to evaluate the psychometric properties of a standardized HIV Stigma Scale, translated to Spanish, including its factor structure.

Relationships between functional alpha and beta diversities of flea parasites and their small mammalian hosts.

We studied the relationships between functional alpha and beta diversities of fleas and their small mammalian hosts in 4 biogeographic realms (the Afrotropics, the Nearctic, the Neotropics and the Palearctic), considering 3 components of alpha diversity (functional richness, divergence and regularity). We asked whether (a) flea alpha and beta diversities are driven by host alpha and beta diversities; (b) the variation in the off-host environment affects variation in flea alpha and beta diversities; and (c) the pattern of the relationship between flea and host alpha or beta diversities differs between geographic realms. We analysed alpha diversity using modified phylogenetic generalized least squares and beta diversity using modified phylogenetic generalized dissimilarity modelling.

Tumor growth for remodeling process: A 2D approach.

This paper aims to present a comprehensive framework for coupling tumor-bone remodeling processes in a 2-dimensional geometry. This is achieved by introducing a bio-inspired damage that represents the growing tumor, which subsequently affects the main populations involved in the remodeling process, namely, osteoclasts, osteoblasts, and bone tissue. The model is constructed using a set of differential equations based on the Komarova's and Ayati's models, modified to incorporate the bio-inspired damage that may result in tumor mass formation.

Feasibility, acceptability and impact of a clinical decision support tool among primary care providers in an urban, rural and remote site in the Philippines.

Introduction: Strengthening primary care helps address health inequities that continue to persist in the Philippines. The Philippine Primary Care Studies pilot-tested interventions to improve the primary care system. One intervention was the provision of a free subscription to an electronic decision support application called UpToDate (UTD) for primary care providers (PCPs), including doctors, nurses, midwives and community health workers (CHWs).

In vitro evaluation of methanol extracts of edible fungi Pleurotus ostreatus and Lentinula edodes against Rhyssomatus nigerrimus Fahraeus.

The study aimed to evaluate the insecticidal activity of extracts of edible mushrooms Pleurotus ostreatus and Lentinula edodes against Rhyssomatus nigerrimus. Methanol:water extracts (70:30) of P. ostreatus and L.

First-generation bypass surgery for a giant fusiform aneurysm of the middle cerebral artery: an illustrative case and surgical video.

Giant fusiform aneurysms of the middle cerebral artery (MCA) are complex and rare vascular lesions with a poor natural history and challenging treatment decision-making. We report the case of a 46-year-old male with a history of chronic hypertension and a transient ischemic attack who presented with left-sided hemiparesis. A cerebral angiotomography revealed an unruptured giant fusiform aneurysm in the M2 segment of the right MCA.

Environmental predictors of concentration at marine beaches in Vancouver, Canada: a Bayesian mixed-effects modelling analysis.

Understanding historical environmental determinants associated with the risk of elevated marine water contamination could enhance monitoring marine beaches in a Canadian setting, which can also inform predictive marine water quality models and ongoing climate change preparedness efforts. This study aimed to assess the combination of environmental factors that best predicts ( concentration at public beaches in Metro Vancouver, British Columbia, by combining the region's microbial water quality data and publicly available environmental data from 2013 to 2021. We developed a Bayesian log-normal mixed-effects regression model to evaluate predictors of geometric concentrations at 15 beaches in the Metro Vancouver Region.