Evidence-based obstetric guidance in the setting of a global intravenous fluid shortage.

Intravenous fluid (IVF) administration is a ubiquitous medical intervention. Although there are clear benefits to IVF in certain obstetric scenarios, IVF is often given in unindicated circumstances; the ongoing IVF shortage highlights an opportunity to reduce unindicated IVF in obstetrics. This document provides evidence-based recommendations to reduce IVF use within general obstetric practice.

De novo missense variants in the PP2A regulatory subunit PPP2R2B in a neurodevelopmental syndrome: potential links to mitochondrial dynamics and spinocerebellar ataxias.

The heterotrimeric protein phosphatase 2A (PP2A) complex catalyzes about half of Ser/Thr dephosphorylations in eukaryotic cells. A CAG repeat expansion in the neuron-specific protein PP2A regulatory subunit PPP2R2B gene causes spinocerebellar ataxia type 12 (SCA12). We established five monoallelic missense variants in PPP2R2B (four confirmed as de novo) as a cause of intellectual disability with developmental delay (R149P, T246K, N310K, E37K, I427T).

The persistent effects of predator odor stressor enhance interoceptive sensitivity to alcohol through GABA receptor adaptations in the prelimbic cortex in male, but not female rats.

Background: Traumatic stress is associated with high rates of problematic alcohol use, but how the persistent effects of trauma impact sensitivity to alcohol remain unknown. This study examined the persistent effects of traumatic stress exposure on sensitivity to alcohol and underlying neurobiological mechanisms in rats.

Methods: Male (N=98) and female (N=98) Long-Evans rats were exposed to the predator odor TMT, and two weeks later, molecular, neuronal, and behavioral sensitivity to alcohol were assessed.

Combination of polymeric micelle formulation of TGFβ receptor inhibitors and paclitaxel produces consistent response across different mouse models of Triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is notoriously difficult to treat due to the lack of targetable receptors and sometimes poor response to chemotherapy. The transforming growth factor beta (TGFβ) family of proteins and their receptors (TGFRs) are highly expressed in TNBC and implicated in chemotherapy-induced cancer stemness. Here, we evaluated combination treatments using experimental TGFR inhibitors (TGFβi), SB525334 (SB), and LY2109761 (LY) with paclitaxel (PTX) chemotherapy.

Siglec15/TGF-β bispecific antibody mediates synergistic anti-tumor response against 4T1 triple negative breast cancer in mice.

An ideal tumor-specific immunomodulatory therapy should both preferentially target the tumor, while simultaneously reduce the immunosuppressive environment within the tumor. This guiding principle led us to explore engineering Siglec-15 (S15) targeted bispecific antibody (bsAb) to enhance therapy against triple negative breast cancer (TNBC). S15 appears to be exclusively expressed on macrophages and diverse tumor cells, including human and mouse 4T1 TNBC.

In situ-crosslinked Zippersomes enhance cardiac repair by increasing accumulation and retention.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here, we show that EVs decorated with the next-generation of high-affinity (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7-fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs.

Association between tumor location and toxicity outcomes after stereotactic radiosurgery for brain metastases.

Purpose: Toxicities associated with stereotactic radiosurgery (SRS) are important when considering treatment and supportive management for patients with brain metastases. We herein assessed the association between brain metastasis location and risk of toxicity after SRS.

Methods: We conducted a retrospective institutional review of patients treated with SRS for brain metastases between 2008 and 2023.

Interleukin-12 decorated nanosized semiflexible Immunofilaments enable directed targeting and augmented IFNγ responses of natural killer cells.

Immunotherapies are a powerful strategy to treat cancer by modulating the immune system to raise an anti-tumor immune response. A prime example of immunotherapies are cytokines - small immunomodulatory molecules that are widely used to stimulate immune cells. Undirected administration of cytokines, however, can cause severe side effects, preventing the use of potent cytokines, such as Interleukin (IL)-12, which induces IFNγ responses by cytotoxic effector lymphocytes, including NK cells.

Strengthening Community Responses to Economic vulnerability (SeCuRE): a protocol of an HIV status-neutral pilot randomized clinical trial with transgender women of color in Detroit, Michigan.

Background: In the United States (US), transgender women of color experience cyclical, interlocking systems of structural and institutional oppression rooted in racism and transphobia, which fuel economic vulnerability. Together, cycles of intersecting racism, transphobia, and economic vulnerability create conditions that give rise to extreme HIV inequities among transgender women of color. Microeconomic interventions - designed to improve financial standing by increasing income generation and access to financial resources through entrepreneurship, cash transfers, and training - have the potential to address structural factors underlying HIV inequities.

Enabling Fast Photoresponse in Hybrid Perovskite/MoS Photodetectors by Separating Local Photocharge Generation and Recombination.

Interfacing CHNHPbI (MAPbI) with 2D van der Waals materials in lateral photodetectors can suppress the dark current and driving voltage, while the interlayer charge separation also renders slower charge dynamics. In this work, we show that more than one order of magnitude faster photoresponse time can be achieved in MAPbI/MoS lateral photodetectors by locally separating the photocharge generation and recombination through a parallel channel of single-layer MAPbI. Photocurrent () mapping reveals electron diffusion lengths of about 20 μm in single-layer MAPbI and 4 μm in the MAPbI/MoS heterostructure.

Analysis of 2019 Ohio Disease Intervention Specialist (DIS) Records for Syphilis Cases Using Clustering Algorithms.

Background: Developments in natural language processing (NLP) and unsupervised machine learning methodologies (e.g., clustering) have given researchers new tools to analyze both structured and unstructured health data.

Are testosterone pulses a physiological mechanism for expanding activity beyond territories?

We ask whether artificially induced testosterone pulses (T-pulses), administered to males in the wild at the territory boundary, adjust location preferences within the territory. Multiple transient T-pulses occurring after social interactions in males can alter behaviour and spatial preferences. We previously found that T-pulses administered at the nest induce male California mice, a biparental and territorial species, to spend more time at the nest likely through conditioned place preferences.

Thoughtful data analysis.

The acceleration in the field of data science is well known [see, e.g., D.

Studies of Artificial Intelligence/Machine Learning Registered on ClinicalTrials.gov: Cross-Sectional Study With Temporal Trends, 2010-2023.

Background: The rapid growth of research in artificial intelligence (AI) and machine learning (ML) continues. However, it is unclear whether this growth reflects an increase in desirable study attributes or merely perpetuates the same issues previously raised in the literature.

Objective: This study aims to evaluate temporal trends in AI/ML studies over time and identify variations that are not apparent from aggregated totals at a single point in time.

A plain language summary of the final analysis of the GRIFFIN study of daratumumab plus lenalidomide, bortezomib, and dexamethasone for people with newly diagnosed multiple myeloma.

What Is This Summary About?: This summary describes the final analysis of the GRIFFIN study. In this study, participants were newly diagnosed with a type of blood and bone marrow cancer called multiple myeloma, had never received any treatment, and were able to undergo an autologous stem cell transplant. The GRIFFIN study looked at adding the drug daratumumab (D) to a combination of standard treatments called RVd (lenalidomide [R], bortezomib [V], and dexamethasone [d]) during the treatment phases induction and consolidation, followed by daratumumab and lenalidomide (D-R) maintenance.