Penalized G-estimation for effect modifier selection in a structural nested mean model for repeated outcomes.

Effect modification occurs when the impact of the treatment on an outcome varies based on the levels of other covariates known as effect modifiers. Modeling these effect differences is important for etiological goals and for purposes of optimizing treatment. Structural nested mean models (SNMMs) are useful causal models for estimating the potentially heterogeneous effect of a time-varying exposure on the mean of an outcome in the presence of time-varying confounding.

Unveiling the Uncommon: A Case Report of Horner's Syndrome as a Rare Glimpse Into Giant Cell Arteritis.

Giant cell arteritis (GCA) is an inflammatory vasculitis affecting large and medium-sized arteries, leading to complications such as arterial dissection, blindness, and stroke. Rarely, GCA presents with Horner's syndrome due to sympathetic neuron involvement from arterial inflammation. This case report discusses an 82-year-old female with hypertension, atrial fibrillation, and arthritis who presented with a 24 h history of right eye ptosis, blurred vision, dizziness, and aching eye pain.

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

The impact of hemoglobin concentration on farrowing duration in sows.

Concerns have been raised about the prevalence of anemia in sows, yet our understanding of its consequences, particularly its impact on the farrowing process, remains limited. This study investigated the relationship between hemoglobin concentration () and farrowing duration in sows. A total of 101 sows ( = 16 parity 0, 15 parity 1, 24 parity 2, and 46 parity 3 sows) were monitored for blood HbC (Hemocue Hb 201 device) from the ear vein before farrowing (day 112 of gestation) and between 40 to 48 h after farrowing (day 2).

Decoupling of Tree-Ring Cellulose δO and δH Highlighted by Their Contrasting Relationships to Climate and Tree Intrinsic Variables.

Oxygen (δO) and hydrogen (δH) stable isotope ratios are tightly coupled in precipitation and, albeit damped, in leaf water, but are often decoupled in tree-ring cellulose. The environmental and physiological conditions in which this decoupling occurs are not yet well understood. We investigated the relationships between δO and δH and tree-ring width (TRW), tree crown volume, tree age and climate in silver fir and Douglas-fir and found substantial differences between δO and δH.

Chicken meal is not an appropriate reference protein for estimating protein quality of ingredients used in extruded diets intended for dogs.

The indicator amino acid oxidation (IAAO) method has been used to determine metabolic availability (MA) of amino acids in feedstuffs for pigs, humans, and preliminarily for cats. Peas are a commonly used protein source in grain-free extruded dog diets. However, peas have a poor sulfur amino acid (AA) ratio (methionine [Met]:cysteine) with Met being the first limiting AA.

First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of BMS-986308: A Renal Outer Medullary Potassium Channel Inhibitor.

In patients with heart failure (HF) who respond inadequately to loop diuretic therapy, BMS-986308, an oral, selective, reversible renal outer medullary potassium channel (ROMK) inhibitor may represent an effective diuretic with a novel mechanism of action. We present data from the first-in-human study aimed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) following single ascending doses of BMS-986308 in healthy adult participants. Forty healthy participants, aged from 20 to 55 years, and body mass index (BMI) from 19.

Performance of common primary and chromogenic culture media for MALDI-TOF MS identification of clinically relevant yeasts.

Timely and accurate identification of yeasts is essential for adequate treatment, considering the increase in antifungal resistance of some species, particularly for . Current matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) manufacturer's protocol for identification of yeasts requires 24- to 72-h cultivation on Sabouraud dextrose media (SAB), but not some of the mainstay primary culture media used in mycology such as inhibitory mold agar (IMA), Mycosel, CHROMagar Candida Plus, and CHROMagar Candida. As culture media can influence MALDI-TOF MS identification results, this study evaluated the accuracy and performance of identification of clinically relevant yeasts on these first-line media using the VITEK-MS MALDI-TOF MS system.

Meeting the 24-hour movement guidelines among adult immigrants in Canada.

Objectives: The Canadian 24-Hour Movement Guidelines include recommendations for healthy levels of physical activity, sedentary behaviour, and sleep. Meeting these recommendations could help immigrants stay healthy. However, little is known about the movement behaviours of adult immigrants in Canada nor how these differ in relation to non-immigrants or time since immigration.

Myeloid-T cell interplay and cell state transitions associated with checkpoint inhibitor response in melanoma.

Background: The treatment of melanoma, the deadliest form of skin cancer, has greatly benefited from immunotherapy. However, many patients do not show a durable response, which is only partially explained by known resistance mechanisms.

Methods: We performed single-cell RNA sequencing of tumor immune infiltrates and matched peripheral blood mononuclear cells of 22 checkpoint inhibitor (CPI)-naive stage III-IV metastatic melanoma patients.

Autophagy prevents graft failure during murine graft-versus-host disease.

Autophagy is an intracellular survival process that has established roles in the long-term survival and function of hematopoietic stem cells (HSC). We investigated the contribution of autophagy to HSC fitness during allogeneic transplantation and graft-versus-host disease (GVHD). We demonstrate in vitro that both tumor necrosis factor and IL-1β, major components of GVHD cytokine storm, synergistically promote autophagy in both HSC and their more mature hematopoietic progenitor cells (HPC).

Image-guided percutaneous ablation of hepatic epithelioid hemangioendothelioma.

Purpose: Disease control and survival following percutaneous ablation of hepatic epithelioid hemangioendothelioma (EHE) was studied retrospectively.

Methods: Six patients underwent 16 image-guided ablation procedures to treat 35 liver tumors from 2015 to 2022 (17 microwave ablation, 9 irreversible electroporation, 8 cryoablation, and 1 radiofrequency ablation). Technical success, local progression, intrahepatic progression, distant progression, overall survival, and adverse events were assessed.

Crimmigrating Narratives: Examining Third-Party Observations of US Detained Immigration Court.

Examining what we call "crimmigrating narratives," we show that US immigration court criminalizes non-citizens, cements forms of social control, and dispenses punishment in a non-punitive legal setting. Building on theories of crimmigration and a sociology of narrative, we code, categorize, and describe third-party observations of detained immigration court hearings conducted in Fort Snelling, Minnesota, from July 2018 to June 2019. We identify and investigate structural factors of three key crimmigrating narratives in the courtroom: one based on threats (stories of the non-citizen's criminal history and perceived danger to society), a second involving deservingness (stories of the non-citizen's social ties, hardship, and belonging in the United States), and a third pertaining to their status as "impossible subjects" (stories rendering non-citizens "illegal," categorically excludable, and contradictory to the law).

Androgen receptor is a determinant of melanoma targeted drug resistance.

Melanoma provides a primary benchmark for targeted drug therapy. Most melanomas with BRAF mutations regress in response to BRAF/MEK inhibitors (BRAFi/MEKi). However, nearly all relapse within the first two years, and there is a connection between BRAFi/MEKi-resistance and poor response to immune checkpoint therapy.

Antagonistic roles of canonical and Alternative-RPA in disease-associated tandem CAG repeat instability.

Expansions of repeat DNA tracts cause >70 diseases, and ongoing expansions in brains exacerbate disease. During expansion mutations, single-stranded DNAs (ssDNAs) form slipped-DNAs. We find the ssDNA-binding complexes canonical replication protein A (RPA1, RPA2, and RPA3) and Alternative-RPA (RPA1, RPA3, and primate-specific RPA4) are upregulated in Huntington disease and spinocerebellar ataxia type 1 (SCA1) patient brains.

Whole genomes from bacteria collected at diagnostic units around the world 2020.

The Two Weeks in the World research project has resulted in a dataset of 3087 clinically relevant bacterial genomes with pertaining metadata, collected from 59 diagnostic units in 35 countries around the world during 2020. A relational database is available with metadata and summary data from selected bioinformatic analysis, such as species prediction and identification of acquired resistance genes.

Quinone-mediated hydrogen anode for non-aqueous reductive electrosynthesis.

Electrochemical synthesis can provide more sustainable routes to industrial chemicals. Electrosynthetic oxidations may often be performed 'reagent-free', generating hydrogen (H) derived from the substrate as the sole by-product at the counter electrode. Electrosynthetic reductions, however, require an external source of electrons.

Ketolysis drives CD8 T cell effector function through effects on histone acetylation.

Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. Here, we identified ketone bodies (KBs)-including β-hydroxybutyrate (βOHB) and acetoacetate (AcAc)-as essential fuels supporting CD8 T cell metabolism and effector function. βOHB directly increased CD8 T effector (Teff) cell cytokine production and cytolytic activity, and KB oxidation (ketolysis) was required for Teff cell responses to bacterial infection and tumor challenge.

Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment.

Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy.

Excitatory neuron-specific suppression of the integrated stress response contributes to autism-related phenotypes in fragile X syndrome.

Dysregulation of protein synthesis is one of the key mechanisms underlying autism spectrum disorder (ASD). However, the role of a major pathway controlling protein synthesis, the integrated stress response (ISR), in ASD remains poorly understood. Here, we demonstrate that the main arm of the ISR, eIF2α phosphorylation (p-eIF2α), is suppressed in excitatory, but not inhibitory, neurons in a mouse model of fragile X syndrome (FXS; Fmr1).

PET/CT Fluoroscopy during PET/CT-Guided Interventions: Initial Experience.

This study assessed the feasibility and functionality of the use of a high-speed image fusion technology to generate and display positron emission tomography (PET)/computed tomography (CT) fluoroscopic images during PET/CT-guided tumor ablation procedures. Thirteen patients underwent 14 PET/CT-guided ablations for the treatment of 20 tumors. A Food and Drug Administration-cleared multimodal image fusion platform received images pushed from a scanner, followed by near-real-time, nonrigid image registration.