Insights into the flexibility of the domain-linking loop in actinobacterial coproheme decarboxylase through structures and molecular dynamics simulations.

Prokaryotic heme biosynthesis in Gram-positive bacteria follows the coproporphyrin-dependent heme biosynthesis pathway. The last step in this pathway is catalyzed by the enzyme coproheme decarboxylase, which oxidatively transforms two propionate groups into vinyl groups yielding heme b. The catalytic reaction cycle of coproheme decarboxylases exhibits four different states: the apo-form, the substrate (coproheme)-bound form, a transient three-propionate intermediate form (monovinyl, monopropionate deuteroheme; MMD), and the product (heme b)-bound form.

Cryo-EM SPR structures of Salmonella typhimurium ArnC; the key enzyme in lipid-A modification conferring polymyxin resistance.

Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective.

Patient Characteristics, Management and Long-term Outcomes of Patients with Cardiogenic Shock at a Large Safety Net Hospital.

Data regarding cardiogenic shock (CS) from safety-net hospitals serving socioeconomically-disadvantaged patients are limited. In addition, little is known regarding long-term outcomes and management of heart failure-related CS (HF-CS), a population potentially especially vulnerable to adverse social determinants of health (SDOH). A single-center retrospective cohort study of patients with Stage C, D, or E CS at a public safety-net hospital between 2017-2023 was performed.

Characterizing the relationship between personality dimensions and psychosis-specific clinical characteristics.

Background: Past studies associating personality with psychosis have been limited by small nonclinical samples and a focus on general symptom burden. This study uses a large clinical sample to examine personality's relationship with psychosis-specific features and compare personality dimensions across clinically and neurobiologically defined categories of psychoses.

Methods: A total of 1352 participants with schizophrenia, schizoaffective disorder, and bipolar with psychosis, as well as 623 healthy controls (HC), drawn from the Bipolar-Schizophrenia Network for Intermediate Phenotypes (BSNIP-2) study, were included.

Baseline and outcome stereoacuity of children with anisometropic amblyopia undergoing dichoptic amblyopia treatment.

Background: One rationale for dichoptic amblyopia therapy is that it may promote recovery of binocular function. Yet data on binocular outcomes in anisometropic amblyopia following dichoptic therapy are sparse. We report factors associated with pre- and post-treatment binocular function in anisometropic amblyopia, and examine binocular function in children who recover normal visual acuity compared to those with residual amblyopia.

Clinically Meaningful Upstaging and Upgrading in Favorable Intermediate-Risk Radical Prostatectomy Patients.

Introduction: In NCCN favorable intermediate-risk (FIR) prostate cancer (PCa) patients treated with radical prostatectomy (RP), we tested the effect of upstaging and upgrading on cancer-specific mortality (CSM).

Methods: Within the SEER database (2010-2021), upstaging (≥pT3a or pN1) and upgrading (ISUP ≥3) rates in FIR RP patients were tabulated. Kaplan-Meier (KM) plots and multivariable Cox-regression models (CRMs) were fitted.

Imaging of Acute Pulmonary Embolism: An Update.

Imaging is essential in the evaluation and management of acute pulmonary embolism. Advances in multi-energy CT including dual-energy CT and photon-counting CT have allowed faster scans with lower radiation dose and optimal quality. Artificial intelligence has a potential role in triaging potentially positive examinations and could serve as a second reader.

High definition transcranial direct current stimulation as an intervention for cognitive deficits in Alzheimer's dementia: A randomized controlled trial.

Background: Recent disease-modifying treatments for Alzheimer's disease show promise to slow cognitive decline, but show no efficacy towards reducing symptoms already manifested.

Objectives: To investigate the efficacy of a novel noninvasive brain stimulation technique in modulating cognitive functioning in Alzheimer's dementia (AD).

Design: Pilot, randomized, double-blind, parallel, sham-controlled study SETTING: Clinical research site at UT Southwestern Medical Center PARTICIPANTS: Twenty-five participants with clinical diagnoses of AD were enrolled from cognition specialty clinics.

Metabolic profiles of cutaneous lupus have abnormalities in the nicotinamide adenine dinucleotide pathway.

Objective: Metabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous autoimmune diseases, such as cutaneous lupus erythematosus (CLE), is less well studied. An improved understanding of the metabolic pathways dysregulated in CLE may lead to novel treatment options, biomarkers and insights into disease pathogenesis. The objective was to compare metabolomic profiles in the skin and sera of CLE and control patients using liquid chromatography-mass spectrometry (LC-MS).

Structures and mRNP remodeling mechanism of the TREX-2 complex.

mRNAs are packaged with proteins into messenger ribonucleoprotein complexes (mRNPs) in the nucleus. mRNP assembly and export are of fundamental importance for all eukaryotic gene expression. Before export to the cytoplasm, mRNPs undergo dynamic remodeling governed by the DEAD-box helicase DDX39B (yeast Sub2).

Dietary Interventions, Supplements, and Plant-Derived Compounds for Adjunct Vitiligo Management: A Review of the Literature.

Vitiligo is a chronic autoimmune pigmentation disorder shaped by a complex interplay of genetic predispositions and environmental triggers. While conventional therapies-phototherapy, corticosteroids, and immunosuppressants-can be effective, their benefits are often partial and temporary, with recurrence common once treatment stops. As such, there is increasing interest in exploring complementary approaches that may offer a more sustainable impact.

An Updated Systematic Review and Network Meta-Analysis of First-Line Triplet vs. Doublet Therapies for Metastatic Hormone-Sensitive Prostate Cancer.

: The addition of androgen receptor pathway inhibitors (ARPIs) to androgen deprivation therapy (ADT), with or without docetaxel (Doc), is currently recommended for metastatic, hormone-sensitive prostate cancer (mHSPC). Recently, the ARANOTE trial evaluated the efficacy and safety of Darolutamide + ADT in this setting. We aimed to update a network meta-analysis (NMA) of these combination therapies.

Development of a checklist for cognitive assessment requirements (CARE) based on a Delphi consensus study.

Situational factors can influence cognitive performance and should be considered for conducting cognitive assessments. The objective of this project was to develop a checklist for Cognitive Assessment Requirements (CARE) to identify these situational factors before conducting cognitive assessments and account for them. This study employed a four-round Delphi approach involving 22 experts to identify situational factors that can impact cognitive assessment results.

A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

Association of an HIV-Prediction Model with Uptake of Pre-Exposure Prophylaxis (PrEP).

Background: Global efforts aimed at ending human immunodeficiency virus (HIV) incidence have adapted and evolved since the turn of the century. The utilization of machine learning incorporated into an electronic health record (EHR) can be refined into prediction models that identify when an individual is at greater HIV infection risk. This can create a novel and innovative approach to identifying patients eligible for preventative therapy.

Application of an Externally Developed Algorithm to Identify Research Cases and Controls from Electronic Health Record Data: Failures and Successes.

Background: The use of Electronic Health Records (EHRs) in research demands robust, interoperable systems. By linking biorepositories to EHR algorithms, researchers can efficiently identify cases and controls for large observational studies (e.g.

Implications of packed red bloods cells production and transfer on post transfusion hemoglobin increase.

Background: Blood loss resulting in severe anemia is the most common indication for postoperative allogenic red blood cell (RBC) transfusions. In high-income countries, the majority of transfusions is received by elderly patients. Preservatives extend the storage of RBCs, though concerns exist about potential harm from transfusing older RBCs.

The influence of patient gender on exercise prescription in ACL reconstruction rehabilitation.

Objective: To assess differences in physical therapists' exercise prescription and confidence in return-to-sport readiness between girl and boy patients undergoing rehabilitation post-ACLR.

Design: Cross-sectional survey.

Methods: 115 physical therapist responses were collected in an electronic survey.

Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258.

Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT).

Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status.

Finding Value in Pediatric Liver Transplantation: When Does Volume Matter?

Introduction: Pediatric liver transplantation provides substantial survival benefit. An emphasis on value-based practices has become a central theme in many surgical fields, but have not been well-studied in pediatric transplantation. Given an increasing focus on optimizing outcomes while containing costs, defining value in pediatric liver transplantation warrants investigation.

Cryo-EM structure and regulation of human NAD kinase.

Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a crucial reducing cofactor for reductive biosynthesis and protection from oxidative stress. To fulfill their heightened anabolic and reductive power demands, cancer cells must boost their NADPH production. Progrowth and mitogenic protein kinases promote the activity of cytosolic NAD kinase (NADK), which produces NADP, a limiting NADPH precursor.

Romosozumab Improves Tissue Thickness-Adjusted Trabecular Bone Score in Women With Osteoporosis and Diabetes.

Context: Trabecular bone score (TBS), a gray-level texture index derived from lumbar spine (LS) dual-energy x-ray absorptiometry (DXA) scans, is decreased in patients with diabetes and is associated with increased fracture risk, independent of areal bone mineral density (aBMD), but potentially influenced by abdominal fat tissue.

Objective: Evaluate effect of romosozumab (210 mg monthly) for 12 months followed by alendronate (70 mg weekly) for 24 months vs alendronate alone (70 mg weekly) for 36 months on LS aBMD and TBS in women with type 2 diabetes (T2D) enrolled in the ARCH study.

Methods: This post hoc analysis included women from ARCH who had T2D at baseline and LS DXA scans at baseline and ≥1 postbaseline visit (romosozumab-to-alendronate, n = 165; alendronate-to-alendronate, n = 195).

An open chat between Prof Asifa Akhtar and Klaudia Jaczynska.

To mark the International Day of Women and Girls in Science 2025, we invited Prof Asifa Akhtar, Vice President of the Max Planck Society's Biology and Medicine section, Director at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Honorary Professor at the Albert Ludwigs University and recipient of the 2025 FEBS | EMBO Women in Science Award to meet and chat with Klaudia Jaczynska, final year PhD student at Jose Rizo's laboratory in UT Southwestern Medical Center, Dallas, and 2024 FEBS Open Bio Article Prize winner. We invited them to talk about challenges limiting equal representation in science, technology, engineering and mathematics, initiatives to foster supportive environments as a research institute and the importance of highlighting diverse examples of success.

Mcl-1 is a Gatekeeper Molecule to Regulate the Crosstalk Between Ferroptotic Agent-Induced ER Stress and TRAIL-Induced Apoptosis.

We previously reported that ferroptosis interplays with apoptosis through the integration of two independent pathways: the endoplasmic reticulum (ER) stress signaling pathway and the mitochondria-dependent apoptotic signaling pathway. In this study, we investigated a potential gatekeeper molecule, Mcl-1, between the two signal transduction pathways. Morphology studies and cell death analyses confirmed that a combination treatment of ferroptotic agent erastin (ERA) and apoptotic agent TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) synergistically enhances TRAIL-induced apoptosis in human pancreatic adenocarcinoma BxPC3 and human colorectal carcinoma HCT116 cells.