Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study.

Background: Transarterial chemoembolisation (TACE) is standard care for unresectable, non-metastatic hepatocellular carcinoma. We aimed to evaluate the addition of lenvatinib and pembrolizumab to TACE versus dual placebo plus TACE in patients with unresectable, non-metastatic hepatocellular carcinoma.

Methods: In this multicentre, randomised, double-blind, phase 3 study (LEAP-012), patients were recruited from 137 global sites in 33 countries or regions.

A spatiotemporal and machine-learning platform facilitates the manufacturing of hPSC-derived esophageal mucosa.

Human pluripotent stem cell-derived tissue engineering offers great promise for designer cell-based personalized therapeutics, but harnessing such potential requires a deeper understanding of tissue-level interactions. We previously developed a cell replacement manufacturing method for ectoderm-derived skin epithelium. However, it remains challenging to manufacture the endoderm-derived esophageal epithelium despite possessing a similar stratified epithelial structure.

A novel interleukin-10 antibody graft to treat inflammatory bowel disease.

Inflammatory bowel disease (IBD) consists of chronic conditions that severely impact a patient's health and quality of life. Interleukin-10 (IL-10), a potent anti-inflammatory cytokine has strong genetic links to IBD susceptibility and has shown strong efficacy in IBD rodent models, suggesting it has great therapeutic potential. However, when tested in clinical trials for IBD, recombinant human IL-10 (rhIL-10) showed weak and inconsistent efficacy due to its short half-life and pro-inflammatory properties that counteract the anti-inflammatory efficacy.

RBBP6 anchors pre-mRNA 3' end processing to nuclear speckles for efficient gene expression.

Pre-mRNA 3' processing is an integral step in mRNA biogenesis. However, where this process occurs in the nucleus remains unknown. Here, we demonstrate that nuclear speckles (NSs), membraneless organelles enriched with splicing factors, are major sites for pre-mRNA 3' processing in human cells.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Mechanistic basis of temperature adaptation in microtubule dynamics across frog species.

Cellular processes are remarkably effective across diverse temperature ranges, even with highly conserved proteins. In the context of the microtubule cytoskeleton, which is critically involved in a wide range of cellular activities, this is particularly striking, as tubulin is one of the most conserved proteins while microtubule dynamic instability is highly temperature sensitive. Here, we leverage the diversity of natural tubulin variants from three closely related frog species that live at different temperatures.

Gustatory cortex neurons perform reliability-dependent integration of multisensory flavor inputs.

Flavor is the quintessential multisensory experience, combining gustatory, retronasal olfactory, and texture qualities to inform food perception and consumption behavior. However, the computations that govern multisensory integration of flavor components and their underlying neural mechanisms remain elusive. Here, we use rats as a model system to test the hypothesis that taste and smell components of flavor are integrated in a reliability-dependent manner to inform hedonic judgments and that this computation is performed by neurons in the primary taste cortex.

Sequential recruitment of F-BAR proteins controls cytoskeletal crosstalk at the yeast bud neck.

In vivo functions of the septin and actin cytoskeletons are closely intertwined, yet the mechanisms underlying septin-actin crosstalk have remained poorly understood. Here, we show that the yeast-bud-neck-associated Fes/CIP4 homology Bar-amphiphysin-Rvs (F-BAR) protein suppressor of yeast profilin 1 (Syp1)/FCHo uses its intrinsically disordered region (IDR) to directly bind and bundle filamentous actin (F-actin) and to physically link septins and F-actin. Interestingly, the only other F-BAR protein found at the neck during bud development, Hof1, has related activities and also potently inhibits the bud-neck-associated formin Bnr1.

Relationship of Age and Running Biomechanics in Female Recreational Runners.

Middle-age and older runners demonstrate differences in running biomechanics compared with younger runners. Female runners demonstrate differences in running biomechanics compared with males, and females experience hormonal changes during menopause that may also affect age-related changes in running biomechanics. The purpose of this study was to determine the relationship between age and running biomechanics in healthy female recreational runners.

What Is in a Name? Depression and Anxiety Symptoms in Collegiate Athletes With and Without a History of Concussion.

Context: Athletes with a history of concussion (CON) have been demonstrated to have heightened levels of anxiety and depression that may continue well beyond the resolution of concussion symptoms. The global events of 2020 resulted in elevated levels of anxiety and depression in the general population, which may have unequally presented in collegiate athletes with (CON) than those without a history of concussion (NoCON). Using a deception design, our survey-based study compared levels of anxiety and depression in CON and NoCON collegiate athletes in response to the pandemic and social injustices.

Clinician Knowledge of Anterior Cruciate Ligament Reconstruction Rehabilitation Practices: A Preliminary Survey Study.

Context: After completing rehabilitation, patients face a high risk of subsequent injury following anterior cruciate ligament reconstruction. It is important to identify potential barriers to patient success including clinician knowledge. The purpose of this study was to assess clinician knowledge of research related to anterior cruciate ligament reconstruction rehabilitation.

Peak Weight Acceptance, Mid Stance Trough, and Peak Push-Off Force Symmetry Are Decreased in Older Adults Compared With Young Adults.

Gait abnormalities affect an individual's ability to navigate the world independently and occur in 10% of older adults. Examining age-related gait symmetry in nonlaboratory environments is necessary for understanding mobility limitations in older adults. This study examined gait symmetry differences between older and younger adults using in-shoe force sensors.

Joint Associations of Sedentary Time and Intensity-Specific Physical Activity With Cancer Mortality: A Device-Based Cohort Study of 72,458 UK Adults.

Background: There are no studies examining the prospective joint association of device-based measures of sedentary time and physical activity (PA) with cancer mortality. We examined the joint associations of sedentary time and intensity-specific PA with cancer mortality in 72,458 adults from UK Biobank.

Methods: Participants wore an Axivity AX3 accelerometer on their dominant wrist for at least 3 days (with at least 1 weekend day).

The climb toward intracranial efficacy: Zorifertinib in EGFR-mutant NSCLC with CNS metastases in the EVEREST trial.

The phase III EVEREST trial evaluating zorifertinib in the treatment of metastatic EGFR-mutant NSCLC was groundbreaking in its specific inclusion of patients with brain metastases. Zorifertinib prolonged systemic and intracranial progression-free survival compared with first-generation EGFR inhibitors, yet questions remain about its efficacy and toxicity compared with osimertinib.

Integrating CTLA-4/PD-1 blockade into cervical cancer management: Results of COMPASSION-16.

Although there is anti-tumor efficacy of dual CTLA-4/PD-1 blockade in advanced/recurrent cervical cancer, it is unclear whether combination with chemotherapy is synergistic. In COMPASSION-16, Wu et al. demonstrated improved survival outcomes of cadolinimab plus chemotherapy compared to chemotherapy alone for first-line systemic therapy for advanced/recurrent cervical cancer, suggesting a potential role of bispecific CTLA-4/PD-1 inhibitors in the frontline setting.

Belzutifan for renal cell carcinoma: Balancing regulatory approval with societal and patient impact.

LITESPARK-005 evaluated belzutifan against everolimus in advanced renal cell carcinoma (RCC), demonstrating significant progression-free survival improvement but failing to meet the overall survival (OS) co-primary endpoint. Despite FDA approval, the trial highlights key obstacles in drug development in RCC, given the absence of OS improvement, lack of biomarker studies, high financial toxicity, and limited accessibility outside the United States.

Clinical advances of mRNA vaccines for cancer immunotherapy.

The development of mRNA vaccines represents a significant advancement in cancer treatment, with more than 120 clinical trials to date demonstrating their potential across various malignancies, including lung, breast, prostate, melanoma, and more challenging cancers such as pancreatic and brain tumors. These vaccines work by encoding tumor-specific antigens and immune-stimulating molecules, effectively activating the immune system to target and eliminate cancer cells. Despite these promising advancements, significant challenges remain, particularly in achieving efficient delivery and precise regulation of the immune response.

The effects of corticotropin-releasing factor (CRF) and urocortins on the serotonin (hydroxytryptamine, 5HT) released from the raphe nuclei (RN).

Corticotropin-releasing factor (CRF) and urocortins (UCN1, UCN2 and UCN3) belong to the same CRF family of neuropeptides. They regulate the neuroendocrine, autonomic and behavioral responses to stress via two CRF receptors (CRF1 and CRF2). Stress, anxiety and depression affects the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the serotoninergic neurotransmission, both being regulated by CRF and CRF-related peptides.

Lifting of travel restrictions brings additional noise in COVID-19 surveillance through wastewater-based epidemiology in post-pandemic period.

The post-pandemic world still faces ongoing COVID-19 infections, although international travel has returned to pre-pandemic conditions. Wastewater-based epidemiology (WBE) is considered an efficient tool for the population-wide surveillance of COVID-19 infections during the pandemic. However, the performance of WBE in post-pandemic era with travel restrictions lifted remains unknown.

Advancing cultural humility in pharmacy education: Insights from interprofessional experiences for varied learning modalities.

Effective pharmacy education requires incorporating interactive and engaging strategies that encourage collaboration among people from diverse backgrounds. Activities that forward cultural humility in combination with interprofessional education (IPE) are beneficial to achieve a comprehensive educational experience for enhanced patient centered care and effective teamwork between colleagues. Moving beyond travel seminars and Advanced Pharmacy Practice Experiences (APPEs), these goals can be met through numerous educational formats, which can be tailored to the needs of the course using institutional resources available.

A three-dimensional mouse liver organoid platform for assessing EDCs metabolites simulating liver metabolism.

Hepatic metabolism is an important process for evaluate the potential activity and toxicity of endocrine disrupting chemicals (EDCs) metabolites. Organization for Economic Co-operation and Development (OECD) has advocated the development of in vitro assays that mimic in vivo hepatic metabolism to eventually replace classical animal tests. In response to this need, we established a 3D mouse liver organoid (mLO) platform that mimics the animal model and is distinct from existing models.

Cemiplimab in recurrent cervical cancer: Final analysis of overall survival in the phase III EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial.

Aim: Cemiplimab has demonstrated significantly longer survival than physician's choice of chemotherapy in patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. We report the final survival analysis from the phase III randomized study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9).

Methods: Cemiplimab (n = 304) or chemotherapy (n = 304) were administered every 3 weeks.

Association between oral microbiome dysbiosis and Sjogren Syndrome. A systematic review of clinical studies.

Objectives: This systematic review investigates the association of oral microbiome dysbiosis with Sjogren Syndrome (SS).

Materials And Methods: Indexed databases (PubMed/Medline, EMBASE, OVID, Web of Science, and Scopus) were independently searched for relevant manuscripts published until August 2024. Clinical studies on oral microbial flora count and diversity in SS patients were included.

The unfolding of psychological distress following the October 7 attack on Israel: The impact of exposure, gender, and event centrality.

Background: Mass disasters, whether natural or human-made, pose significant public health challenges, with some individuals demonstrating resilience, whereas others experience persistent emotional distress that may meet diagnostic criteria for mental health disorders. We explored key risk factors for distress following the October 7, 2023, Hamas attacks on Israel, focusing on trauma exposure, gender, and event centrality.

Method: A longitudinal study design was used, assessing posttraumatic distress (PTSD), depression, generalized anxiety, event centrality, and functioning at approximately three (T1; n=858) and seven (T2, n=509) months post-attack.