Rapid human oogonia-like cell specification via transcription factor-directed differentiation.

The generation of germline cells from human induced pluripotent stem cells (hiPSCs) represents a milestone toward in vitro gametogenesis. Methods to recapitulate germline development beyond primordial germ cells in vitro have relied on long-term cell culture, such as 3-dimensional organoid co-culture for ~four months. Using a pipeline with highly parallelized screening, this study identifies combinations of TFs that directly and rapidly convert hiPSCs to induced oogonia-like cells (iOLCs).

Trop2-Expression in Correlation to the Molecular Subtype in Vulvar Squamous Cell Carcinomas (VSCC).

Targeted therapy with antibody-drug conjugates (ADCs) has shown promising results in the treatment of various solid tumours. Sacituzumab-govitecan (SG), a humanised anti-Trop2 monoclonal antibody in combination with the cytotoxic topoisomerase I inhibitor SN38, has been approved for the treatment of metastatic triple-negative breast cancer. The treatment approach with SG requires the expression of Trop2 in the tumour cells.

The hummingbird's adipostat: can a simple rule explain torpor frequency and duration in hummingbirds?

Because hummingbirds are small and have an expensive mode of locomotion, they have constrained energy budgets. Torpor is used to buffer against these energetic challenges, but its frequency and duration vary. We measured lipid content, metabolic rates and torpor use in two species of migrating hummingbirds, calliope () and rufous hummingbirds () at a stopover site.

Lower extremity lymphedema in patients with gynecologic cancer: Validation of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) in German language and investigation of lymphedema real-world treatment.

Purpose: The Gynecologic Cancer Lymphedema Questionnaire (GCLQ) is an established patient-reported outcome measure for lower extremity lymphedema (LEL) in gynecologic oncology. We aimed to validate the GCLQ in German language (GCLQ-GER) for lymphedema detection in German-speaking patients and also investigated real-world patterns of lymphedema treatment.

Methods: The GCLQ was translated from English into German in accordance with the standards of a professional translation process.

CHRNA5-A3-B4, CYP2A6, and DBH genetic associations with smoking cessation throughout adulthood within two longitudinal studies of women.

Introduction: Genetic studies of smoking cessation have been limited by short-term follow-up or cross-sectional design. Within seven genes (CHRNA3, CHRNA5, CHRNB2, CHRNB4, DRD2, DBH and CYP2A6) influencing biological mechanisms relevant to smoking, this study aimed to identify single nucleotide polymorphisms (SNPs) associated with smoking cessation throughout up to 38-years of follow-up.

Methods: Participants were from two all-female cohort studies, Nurses' Health Study (NHS) (n = 10,017) and NHS-2 (n = 2,793).

Can We Predict Who Will Experience Adverse Events While Using Smoking Cessation Pharmacotherapy? A Secondary Analysis of the EAGLES Clinical Trial.

Introduction: Concerns about potential side effects remain a barrier to uptake of Food and Drug Administration (FDA)-approved smoking cessation pharmacotherapy [i.e., varenicline, bupropion, nicotine replacement therapy (NRT)].

First results of migoprotafib, a potent and highly selective Src homology-2 domain-containing phosphatase 2 (SHP2) inhibitor in patients with advanced solid tumors.

Src homology-2 domain-containing phosphatase 2 (SHP2) promotes RAS-MAPK signaling and tumorigenesis and is a promising therapeutic target for multiple solid tumors. Migoprotafib is a potent and highly selective SHP2 inhibitor designed for the treatment of RAS-MAPK driven cancers, particularly in combination with other targeted agents. Here we report first-in-human study results of single agent migoprotafib in advanced solid tumor patients.

Cerebral small vessel disease is an independent determinant of dysphagia after acute stroke.

Background: The high incidence of dysphagia after acute stroke is likely the result of cumulative effects of the stroke and pre-stroke brain health. While cerebral small vessel disease (cSVD) is recognized as a marker of compromised brain health, it's unclear which neuroanatomical pathologies of cSVD impact post-stroke dysphagia. We assessed the relation between cSVD pathologies, i.

A Novel Machine Learning Model to Predict Revision ACL Reconstruction Failure in the MARS Cohort.

Background: As machine learning becomes increasingly utilized in orthopaedic clinical research, the application of machine learning methodology to cohort data from the Multicenter ACL Revision Study (MARS) presents a valuable opportunity to translate data into patient-specific insights.

Purpose: To apply novel machine learning methodology to MARS cohort data to determine a predictive model of revision anterior cruciate ligament reconstruction (rACLR) graft failure and features most predictive of failure.

Study Design: Cohort study; Level of evidence, 3.

Surgical Predictors of Clinical Outcome 6 Years After Revision ACL Reconstruction.

Background: Revision anterior cruciate ligament (ACL) reconstruction has been documented to have inferior outcomes compared with primary ACL reconstruction. The reasons why remain unknown.

Purpose: To determine whether surgical factors performed at the time of revision ACL reconstruction can influence a patient's outcome at 6-year follow-up.

Influence of Polymer Film Thickness on Drug Release from Fluidized Bed Coated Pellets and Intended Process and Product Control.

Background/objectives: Coated drug pellets enjoy widespread use in hard gelatine capsules. In heterogeneous pellets, the drug substance is layered onto core pellets. Coatings are often applied to generate a retarded release or an enteric coating.

A Review and Comparative Case Study Analysis of Real-World Evidence in European Regulatory and Health Technology Assessment Decision Making for Oncology Medicines.

Objectives: Real-world evidence (RWE) is valuable in supporting regulatory and health technology assessment (HTA) decisions; however, the actual contribution to approvals remains elusive. This study aimed to review RWE approaches and use in oncology medicine approvals in Europe and understand cohesion and discrepancy in the acceptance of the RWE by the European Medicines Agency (EMA) and European HTA bodies.

Methods: This scoping review involved a search of the EMA database, National Institute for Health and Care Excellence (NICE), Gemeinsamer Bundesausschuss (G-BA), and Haute Autorité de Santé (HAS) websites to identify final reports and appraisals for oncology medicines with references to RWE.

Transgenic expression of human cytochrome P450 2E1 in C. elegans and rat PC-12 cells sensitizes to ethanol-induced locomotor and mitochondrial effects.

Chronic alcohol (ethanol) use is increasing in the United States and has been linked to numerous health issues in multiple organ systems including neurological dysfunction and diseases. Ethanol toxicity is mainly driven by the metabolite acetaldehyde, which is generated through three pathways: alcohol dehydrogenase (ADH2), catalase (CAT), and cytochrome P450 2E1 (CYP2E1). ADH2, while the main ethanol clearance pathway in the liver, is not expressed in the mammalian brain, resulting in CAT and CYP2E1 driving local metabolism of ethanol in the central nervous system.

2024 Kappa Delta Ann Doner Vaughan Award: Nonsurgical Treatment of Symptomatic, Atraumatic Full-Thickness Rotator Cuff Tears-a Prospective Multicenter Cohort Study With 10-Year Follow-Up.

The Multicenter Orthopaedic Outcomes Network Shoulder Group conducted a prospective cohort study of 452 patients with symptomatic atraumatic rotator cuff tears treated with a physical therapy program to determine the predictors of failure of nonsurgical treatment, to provide insight into indications for surgery. After 10 years, we found the following: (1) Physical therapy was effective for over 70% of patients. (2) PROMs showed statistical and clinical improvement after 12 weeks of therapy and did not decline over 10 years.

Decision Making of the In-season Athlete with Anterior Shoulder Instability.

In-season management of anterior shoulder instability in athletes is a complex problem. Athletes often wish to play through their current season, though recurrent instability rates are high, particularly in contact sports. Athletes are generally considered safe to return to play when they are relatively pain-free, and their strength and range of motion match the uninjured extremity.

A Dataset for Detection and Segmentation of Underwater Marine Debris in Shallow Waters.

Robust object detection is crucial for automating underwater marine debris collection. While supervised deep learning achieves state-of-the-art performance in discriminative tasks, replicating this success on underwater data is challenging. The generalization of these methods suffers due to a lack of available annotated data considering different sources of variation in the unstructured underwater environment and imaging conditions.

Neurocognitive Latent Factors Associate With Early Tobacco and Alcohol Use Among Adolescent Brain Cognitive Development Study Youth.

Purpose: Prospective associations between preadolescent neurocognitive structure and onset of substance use in adolescence have not been examined. This study investigated associations between cognitive structure among youth aged 9 - 10 years and the likelihood of experimentation with tobacco and alcohol by ages 13-14 years.

Methods: A principal component (PC) analysis of nine neurocognitive assessments was used to identify the cognitive structure of unrelated adolescent brain cognitive development study participants (n = 9,655).

Utility of Quadratus Lumborum Blocks in Patients Who Undergo Liver Transplant: A Single-Center Retrospective Study.

Background: Regional anesthesia is an alternative to opioids for pain in patients undergoing liver transplantation. Quadratus lumborum blocks may provide appropriate dermatomal coverage with an excellent safety profile.

Methods: Data were collected retrospectively on adult patients who underwent liver transplant at an academic medical center from 2019 to 2022 (n = 207).

Utilization of Telemedicine to Supervise Medical Students in the Post-Acute/Long-Term Care Setting.

Objectives: Telemedicine has become a widely accepted alternative to face-to-face patient encounters. Although there have been several peer-reviewed journal articles on incorporating telemedicine into the medical school curriculum, particularly during the COVID-19 pandemic, assessments of the effectiveness of remote supervision of medical students have not been reported. This prospective cohort study of student subjects using observational survey data evaluated the efficacy of telemedicine as an educational resource by comparing learning outcomes between osteopathic medical students receiving direct (physically present) supervision with a group who received remote (telemedicine) supervision by clinical faculty within a post-acute/long-term care (PA/LTC) setting.

Functional role of metabolic suppression in avian thermoregulation in the heat.

Hypometabolism arising from active metabolic suppression occurs in several contexts among endotherms, particularly during heterothermic states such as torpor. However, observed Q ≈ 1 for avian resting metabolic rate within the thermoneutral zone, values far below the Q = 2-3 expected on the basis of Arrhenius effects, suggests hypometabolism also plays a role in birds' thermoregulation at environmental temperatures approaching or exceeding normothermic body temperature (T). We evaluated the occurrence of hypometabolism during heat exposure among birds by re-analysing literature data to quantify changes in T and resting metabolic rate (RMR) near the upper boundary of the thermoneutral zone, at air temperatures (T) between the inflection above which T increases above normothermic levels (T) and the upper critical limit of thermoneutrality (T).