Pre-treatment Pulmonary Function Testing Has Limited Utility In B-cell Lymphoma Treated with CD19 CAR T-cells.

Pulmonary function tests (PFT) are recommended for hematopoietic cell transplantation (HCT) evaluation. However, their prognostic value in chimeric antigen receptor T-cell (CAR-T) therapy remains unclear. We assessed the predictive significance of PFTs and pulmonary comorbidity classifications, per the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), in B-cell lymphoma patients undergoing autologous CD19-CAR-T therapy.

Navigating performance measures for ambulatory antimicrobial stewardship: a review of HEDIS® and other metrics the steward should know.

Ambulatory antimicrobial stewardship can be challenging due to disparities in resource allocation across the care continuum, competing priorities for ambulatory prescribers, ineffective communication strategies, and lack of incentive to prioritize antimicrobial stewardship program (ASP) initiatives. Efforts to monitor and compare outpatient antibiotic usage metrics have been implemented through quality measures (QM). Healthcare Effectiveness Data and Information Set (HEDIS®) represent standardized measures that examine the quality of antibiotic prescribing by region and across insurance health plans.

FcRn-dependent IgG accumulation in adipose tissue unmasks obesity pathophysiology.

Immunoglobulin G (IgG) is traditionally recognized as a plasma protein that neutralizes antigens for immune defense. However, our research demonstrates that IgG predominantly accumulates in adipose tissue during obesity development, triggering insulin resistance and macrophage infiltration. This accumulation is governed by neonatal Fc receptor (FcRn)-dependent recycling, orchestrated in adipose progenitor cells and macrophages during the early and late stages of diet-induced obesity (DIO), respectively.

The (mis)use of evidence in contested rights: commentary on the UN Special Rapporteur on violence against women and girls' report on "prostitution and violence".

Readers of Sexual and Reproductive Health Matter are no strangers to interrogating evidence in all its forms, assessing which claims it can support, and about challenges and uncertainties in international norms in the fields of sexual and reproductive rights and health. Questions of evidence, positionality and the role of testimony are particularly live in the context of sex work and human rights. As an exploration about good and bad practices in research and evidence, in this Commentary we highlight the errors, mistakes and wrongly shaped conclusions arising in the recent report by the UN Special Rapporteur on violence against women and girls about prostitution law, sex worker health and rights, and the status of international human rights law on sex work and trafficking.

Environment- and Conformation-Induced Frequency Shifts of C-D Vibrational Stark Probes in NAD(P)H Cofactors.

NAD(P)H cofactors are found in all forms of life and are essential for electron and hydrogen atom transfer. The linear response of a carbon-deuterium (C-D) vibration based on the vibrational Stark effect can facilitate measurements of electric fields for critical biological reactions including cofactor-mediated hydride transfer. We find both inter- and intramolecular electric fields influence the C-D frequency in NAD(P)H and nicotinamide-like models where the reactive C4-hydrogen has been deuterated.

Attracting medical school graduates to residency programs in remotely located hospitals: the challenge lies beyond financial incentives.

Background: Recruitment to residency programs in hospitals located in other than major hubs ("remotely located") is a challenge in many countries. In 2011, the Israeli Ministry of Health launched a 10-year financial incentive to encourage physicians to enroll in residency programs in such hospitals. Nearly 1 billion New Israeli Shekels (260 million US$) were invested in that program which had only limited success.

Transparent and Conformal Microcoil Arrays for Spatially Selective Neuronal Activation.

Micromagnetic stimulation (μMS) using small, implantable microcoils is a promising method for achieving neuronal activation with high spatial resolution and low toxicity. Herein, we report a microcoil array for localized activation of cortical neurons and retinal ganglion cells. We developed a computational model to relate the electric field gradient (activating function) to the geometry and arrangement of microcoils, and selected a design that produced an anisotropic region of activation <50 μm wide.

Protein surface chemistry encodes an adaptive tolerance to desiccation.

Cellular desiccation - the loss of nearly all water from the cell - is a recurring stress in an increasing number of ecosystems that can drive protein unfolding and aggregation. For cells to survive, at least some of the proteome must resume function upon rehydration. Which proteins tolerate desiccation, and the molecular determinants that underlie this tolerance, are largely unknown.

Biliary atresia: insights into mechanisms using a toxic model of the disease including Wnt and Hippo signaling pathways and microtubules.

Background: Mechanisms underlying bile duct injury in biliary atresia (BA) remain unclear and mechanisms of bile duct repair are unknown. This study aimed to explore the roles of microtubule instability and Wnt and Hippo signaling pathways in a biliatresone-induced BA model.

Methods: Using primary murine neonatal cholangiocytes in both 2D and 3D cultures, and ex-vivo extra hepatic bile ducts (EHBD) which also has peri-cholangiocyte area, we analyzed injury and recovery processes.

Membrane depolarization mediates both the inhibition of neural activity and cell-type-differences in response to high-frequency stimulation.

Neuromodulation using high frequency (>1 kHz) electric stimulation (HFS) enables preferential activation or inhibition of individual neural types, offering the possibility of more effective treatments across a broad spectrum of neurological diseases. To improve effectiveness, it is important to better understand the mechanisms governing activation and inhibition with HFS so that selectivity can be optimized. In this study, we measure the membrane potential (V) and spiking responses of ON and OFF α-sustained retinal ganglion cells (RGCs) to a wide range of stimulus frequencies (100-2500 Hz) and amplitudes (10-100 µA).

FLiPPR: A Processor for Limited Proteolysis (LiP) Mass Spectrometry Data Sets Built on FragPipe.

Here, we present FLiPPR, or FragPipe LiP (limited proteolysis) Processor, a tool that facilitates the analysis of data from limited proteolysis mass spectrometry (LiP-MS) experiments following primary search and quantification in FragPipe. LiP-MS has emerged as a method that can provide proteome-wide information on protein structure and has been applied to a range of biological and biophysical questions. Although LiP-MS can be carried out with standard laboratory reagents and mass spectrometers, analyzing the data can be slow and poses unique challenges compared to typical quantitative proteomics workflows.

linc-ADAIN, a human adipose lincRNA, regulates adipogenesis by modulating KLF5 and IL-8 mRNA stability.

Adipose tissue remodeling and dysfunction, characterized by elevated inflammation and insulin resistance, play a central role in obesity-related development of type 2 diabetes (T2D) and cardiovascular diseases. Long intergenic non-coding RNAs (lincRNAs) are important regulators of cellular functions. Here, we describe the functions of linc-ADAIN (adipose anti-inflammatory), an adipose lincRNA that is downregulated in white adipose tissue of obese humans.

Association of preoperative beta-blocker use and cardiac complications after major noncardiac surgery: a prospective cohort study.

Introduction: Cardiac complications after major noncardiac surgery are common and associated with high morbidity and mortality. How preoperative use of beta-blockers may impact perioperative cardiac complications remains unclear.

Methods: In a multicentre prospective cohort study, preoperative beta-blocker use was ascertained in consecutive patients at elevated cardiovascular risk undergoing major noncardiac surgery.

Management of acute exacerbations of COPD in the emergency department and its associations with clinical variables.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause for emergency department (ED) visits. Still, large scale studies that assess the management of AECOPD in the ED are limited. Our aim was to evaluate treatment characteristics of AE-COPD in the ED on a national scale.

Synonymous Mutations Can Alter Protein Dimerization Through Localized Interface Misfolding Involving Self-entanglements.

Synonymous mutations in messenger RNAs (mRNAs) can reduce protein-protein binding substantially without changing the protein's amino acid sequence. Here, we use coarse-grain simulations of protein synthesis, post-translational dynamics, and dimerization to understand how synonymous mutations can influence the dimerization of two E. coli homodimers, oligoribonuclease and ribonuclease T.

Tissue markers may predict treatment response to antitumor necrosis factor-α agents in children with Crohn's disease.

Objectives: Patients with moderate-severe Crohn's disease (CD) who are treated with antitumor necrosis factor alpha (TNF-α) agents may be subjected to primary nonresponse or partial response. We aimed to identify tissue markers that may predict response to these agents.

Methods: Pediatric patients (6-18 years) with either ileal or ileo-colonic CD who were treated with anti-TNF-α were stratified into three different groups based on their overall response to therapy at the end of induction including clinical and laboratory parameters (group 1-full responders [FR], group 2-partial responders [PR], group 3-nonresponders [NR]).

Neural activity of retinal ganglion cells under continuous, dynamically-modulated high frequency electrical stimulation.

Current retinal prosthetics are limited in their ability to precisely control firing patterns of functionally distinct retinal ganglion cell (RGC) types. The aim of this study was to characterise RGC responses to continuous, kilohertz-frequency-varying stimulation to assess its utility in controlling RGC activity.We usedpatch-clamp experiments to assess electrically-evoked ON and OFF RGC responses to frequency-varying pulse train sequences.

Flexible, scalable, high channel count stereo-electrode for recording in the human brain.

Over the past decade, stereotactically placed electrodes have become the gold standard for deep brain recording and stimulation for a wide variety of neurological and psychiatric diseases. Current electrodes, however, are limited in their spatial resolution and ability to record from small populations of neurons, let alone individual neurons. Here, we report on an innovative, customizable, monolithically integrated human-grade flexible depth electrode capable of recording from up to 128 channels and able to record at a depth of 10 cm in brain tissue.

Fecal microbiota transplantation in capsules for the treatment of steroid refractory and steroid dependent acute graft vs. host disease: a pilot study.

Acute graft-versus-host disease (aGvHD) is a serious complication of allogeneic hematopoietic stem-cell transplantation with limited treatment options. The gut microbiome plays a critical role in aGvHD pathogenesis. Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach to restore gut microbial diversity.