3D polycatenated architected materials.

Architected materials derive their properties from the geometric arrangement of their internal structural elements. Their designs rely on continuous networks of members to control the global mechanical behavior of the bulk. In this study, we introduce a class of materials that consist of discrete concatenated rings or cage particles interlocked in three-dimensional networks, forming polycatenated architected materials (PAMs).

at Sterkfontein did not consume substantial mammalian meat.

Incorporation of animal-based foods into early hominin diets has been hypothesized to be a major catalyst of many important evolutionary events, including brain expansion. However, direct evidence of the onset and evolution of animal resource consumption in hominins remains elusive. The nitrogen-15 to nitrogen-14 ratio of collagen provides trophic information about individuals in modern and geologically recent ecosystems (<200,000 years ago), but diagenetic loss of this organic matter precludes studies of greater age.

Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis.

Myostatin is a paracrine myokine that regulates muscle mass in a variety of species, including humans. In this work, we report a functional role for myostatin as an endocrine hormone that directly promotes pituitary follicle-stimulating hormone (FSH) synthesis and thereby ovarian function in mice. Previously, this FSH-stimulating role was attributed to other members of the transforming growth factor-β family, the activins.

Looped Penrose Drainages of Acute Hand Infections in Vulnerable Populations.

Purpose: Acute hand infections (AHIs) remain a challenge for hand surgeons and represent a condition for which clinical outcomes are considerably affected by social barriers. We previously described the looped Penrose drainage technique, where a drain is sutured to itself in a loop and the outflow tract of egress is maintained, thus obviating the need for large incisions, wound closure, or repeat packing, thereby reducing the follow-up burden. In the face of escalating numbers of socioeconomically vulnerable patients, especially in urban settings, we aimed to characterize the clinical features and outcomes of this technique in an urban population of patients with AHI.

The Management of Upper-Extremity Xylazine-Associated Wounds.

Purpose: Xylazine has been associated with necrotic soft tissue wounds that have placed a challenging burden on patients who inject drugs in the Philadelphia region's health care system over the last few years. An analysis of our initial experience is being presented to guide future treatment and directions for future research.

Methods: A retrospective review of 55 patients with patient-reported xylazine use and associated upper-extremity wounds at a single institution was performed.

Strengthening serological studies: the need for greater geographical diversity, biobanking, and data-accessibility.

Serological studies uniquely strengthen infectious disease surveillance, expanding prevalence estimates to encompass asymptomatic infections, and revealing the otherwise inapparent landscape of immunity, including who is and is not susceptible to infection. They are thus a powerful complement to often incomplete epidemiological and public health measures (administrative measures of vaccination coverage, incidence estimates, etc.).

Impact of Treatment With Trifluridine/Tipiracil in Combination With Bevacizumab on Health-Related Quality of Life and Performance Status in Refractory Metastatic Colorectal Cancer: An Analysis of the Phase III SUNLIGHT Trial.

Background: The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared to FTD/TPI for treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. This analysis of SUNLIGHT investigated the impact of treatment with FTD/TPI + bevacizumab on patient quality of life (QoL) and Eastern Cooperative Oncology Group performance status (ECOG PS).

Methods: Questionnaires (EORTC QLQ-C30 and EQ-5D-5L) and ECOG PS assessments were conducted at baseline and on Day 1 of each treatment cycle.

Finerenone and new-onset diabetes in heart failure: a prespecified analysis of the FINEARTS-HF trial.

Background: Data on the effect of mineralocorticoid receptor antagonist therapy on HbA levels and new-onset diabetes are conflicting. We aimed to examine the effect of oral finerenone, compared with placebo, on incident diabetes in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF) trial.

Methods: In this randomised, double-blind, placebo-controlled trial, 6001 participants with heart failure with New York Heart Association functional class II-IV, left ventricular ejection fraction 40% or higher, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide levels were randomly assigned to finerenone or placebo, administered orally.

Modeling non-genetic adaptation in tumor cells.

Treatment resistance poses a significant challenge in the care of cancer patients. Hirsch et al. applied computational and genomic approaches, examining gene expression dynamics from a mouse model of melanoma at single-cell resolution to reveal that semi-heritable non-genetic alterations in tumor cell populations confer adaptive resistance to treatment.

Environmental contaminants assessment for frequently harvested migratory waterfowl in the Northeast Atlantic flyway.

Waterfowl serve as indicators of ecosystem health and represent a pathway of contaminant exposure for hunters who consume them. In the northeast Atlantic Flyway, data on baseline contaminant loads in waterfowl are lacking. We assessed five species of commonly harvested (and consumed) waterfowl for mercury, polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans, polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and per- and polyfluoroalkyl substances (PFAS).

The (in)dependence of single-cell data inferences on model constructs.

Recent developments in single-cell analysis have revolutionized basic research and have garnered the attention of the forensic domain. Though single-cell analysis is not new to forensics, the ways in which these data can be generated and interpreted are. Modern interpretation strategies report likelihood ratios that rely on a model of the world that is a simplification of it.

Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS.

Probing the functional constraints of influenza A virus NEP by deep mutational scanning.

The influenza A virus nuclear export protein (NEP) is a multifunctional protein that is essential for the viral life cycle and has very high sequence conservation. However, since the open reading frame of NEP largely overlaps with that of another influenza viral protein, non-structural protein 1, it is difficult to infer the functional constraints of NEP based on sequence conservation analysis. In addition, the N-terminal of NEP is structurally disordered, which further complicates the understanding of its function.

Open-label, phase Ia study of STING agonist BI 1703880 plus ezabenlimab for patients with advanced solid tumors.

BI 1703880, a novel STimulator of INterferon Genes (STING) agonist, has demonstrated preclinical antitumor activity. As STING activation can upregulate programmed death ligand 1 and human leukocyte antigen in tumor cells, a combination of BI 1703880 and an anti-programmed cell death protein 1-antibody, such as ezabenlimab, may improve efficacy. This first-in-human phase Ia study (NCT05471856) is evaluating BI 1703880 plus ezabenlimab in patients with advanced solid tumors.

Electroconvulsive therapy in the treatment of catatonia in a patient with Budd Chiari syndrome: a case report.

Catatonia may manifest as an independent entity or as a feature of a neuropsychiatric or medical illness. While electroconvulsive therapy (ECT) is the gold standard treatment for catatonia, it is typically administered if the patient's symptoms fail to respond to benzodiazepines. We describe the case of a 22-year-old male with Budd Chiari induced cirrhosis and no prior psychiatric history, who presented with symptoms of psychosis and hepatic encephalopathy, was treated in the ICU for multi-factorial delirium, developed symptoms of catatonia that failed to respond to lorazepam, ultimately requiring ECT with a favorable response.

Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).

Coexisting Calcific Aortic Stenosis and Transthyretin Cardiac Amyloidosis: Real-World Evaluation of Clinical Characteristics and Outcomes.

Background: The coexistence of transthyretin cardiac amyloidosis (ATTR-CA) and aortic stenosis (AS) is increasingly recognized, but the clinical consequences are unclear. We aimed to characterize clinical outcomes in AS plus ATTR-CA compared with only AS or ATTR-CA.

Methods And Results: In a retrospective cohort study, patients with AS only, ATTR-CA only, or AS plus ATTR-CA were identified using all-payer claims data (2015-2021).

A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Escalating Oral Doses of Dordaviprone and the Effects of Food on the Bioavailability of Dordaviprone in Healthy Adult Subjects.

Dordaviprone (ONC201) is a novel, small molecule imipridone with antitumor effects in glioma patients. This study evaluated the pharmacokinetics and safety of dordaviprone following single escalating doses (Part A), as a capsule content mixed with applesauce or Gatorade (sports drink) [Part B1]), and with or without food [Part B2]. The most common treatment-emergent adverse events pooled across study parts (Parts A, B1, and B2) were headache, dizziness, and headache, respectively; all were mild.

Lessons learned from 5 years of pegvaliase in US clinics: A case series.

Objective: To provide insights and strategies for pegvaliase management in challenging cases with phenylketonuria (PKU) based on the first 5 years of experience with pegvaliase in real-world clinical practice.

Methods: Twelve PKU experts gathered during a one-day, in-person meeting to discuss clinical cases illustrating important lessons from their experiences treating patients with pegvaliase in real-world clinical practice. Challenges with pegvaliase experienced prior to and during treatment and corresponding strategies to overcome them were discussed.

Prevalence of co-occurring conditions among youths receiving treatment with primary anxiety, ADHD, or depressive disorder diagnoses.

Introduction: Anxiety disorders, depressive disorders, and attention-deficit/hyperactivity disorder (ADHD) are some of the most common conditions that youths (<18 years old) receive mental health treatment for. These conditions are associated with high-risk substance use or substance use disorders (SUDs). This study sought to identify the proportion of youths (<18 years old) with anxiety disorders, depressive disorders, or ADHD as a primary diagnosis in community mental health centers (CMHCs) having co-occurring high-risk substance use or a SUD.

First-line pembrolizumab-axitinib versus sunitinib in metastatic RCC: subgroup analysis of patients enrolled in the phase 3 KEYNOTE-426 in Eastern Asia.

Background: The phase 3 open-label KEYNOTE-426 study demonstrated that first-line pembrolizumab plus axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC) in a global population. This subgroup analysis investigated the efficacy and safety of pembrolizumab-axitinib versus sunitinib in patients enrolled in KEYNOTE-426 in East Asia (Japan, South Korea, and Taiwan).

Methods: Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks with oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off).

Broadband highly efficient source of collimated terahertz radiation driven by an ultrafast optical oscillator.

We demonstrate experimentally an efficient terahertz emitter that consists of a 20 µm thick layer of LiNbO clamped between a fused silica substrate and a Si semicone. A focused laser beam from an ultrafast optical oscillator propagates in the LiNbO layer and emits a Cherenkov cone of terahertz radiation to the Si semicone. The radiation is totally internally reflected by the semicone's convex surface and escapes the semicone through its base as a collimated beam.

Observation of complete energy transfer by orthogonally polarized Raman scattering in a high-birefringence fiber.

This study reports the observation of complete orthogonally polarized Raman scattering (OPRS) in a 1.0-km high-birefringence fiber (HBF). An incident pump pulse at 1560 nm with an energy of 2.