Dose escalation and expansion cohorts in patients with advanced breast cancer in a Phase I study of the CDK7-inhibitor samuraciclib.

Samuraciclib is a selective oral CDK7-inhibitor. A multi-modular, open-label Phase I study to evaluate safety and tolerability of samuraciclib in patients with advanced malignancies was designed (ClinicalTrials.gov: NCT03363893).

Acoustic tweezers for high-throughput single-cell analysis.

Acoustic tweezers provide an effective means for manipulating single cells and particles in a high-throughput, precise, selective and contact-free manner. The adoption of acoustic tweezers in next-generation cellular assays may advance our understanding of biological systems. Here we present a comprehensive set of instructions that guide users through device fabrication, instrumentation setup and data acquisition to study single cells with an experimental throughput that surpasses traditional methods, such as atomic force microscopy and micropipette aspiration, by several orders of magnitude.

Clinical and Demographic Factors Associated With COVID-19, Severe COVID-19, and SARS-CoV-2 Infection in Adults: A Secondary Cross-Protocol Analysis of 4 Randomized Clinical Trials.

Importance: Current data identifying COVID-19 risk factors lack standardized outcomes and insufficiently control for confounders.

Objective: To identify risk factors associated with COVID-19, severe COVID-19, and SARS-CoV-2 infection.

Design, Setting, And Participants: This secondary cross-protocol analysis included 4 multicenter, international, randomized, blinded, placebo-controlled, COVID-19 vaccine efficacy trials with harmonized protocols established by the COVID-19 Prevention Network.

Rampant asexual reproduction and limited dispersal in a mangrove population of the coral .

Corals are critical to marine biodiversity. Reproduction and dispersal are key to their resilience, but rarely quantified in nature. Exploiting a unique system-a fully censused, longitudinally characterized, semi-isolated population inhabiting mangroves-we used 2bRAD sequencing to demonstrate that rampant asexual reproduction most likely via parthenogenesis and limited dispersal enable the persistence of a natural population of thin-finger coral ().

Facile mechanochemical cycloreversion of polymer cross-linkers enhances tear resistance.

The mechanical properties of covalent polymer networks often arise from the permanent end-linking or cross-linking of polymer strands, and molecular linkers that break more easily would likely produce materials that require less energy to tear. We report that cyclobutane-based mechanophore cross-linkers that break through force-triggered cycloreversion lead to networks that are up to nine times as tough as conventional analogs. The response is attributed to a combination of long, strong primary polymer strands and cross-linker scission forces that are approximately fivefold smaller than control cross-linkers at the same timescales.

Efficacy of a hybrid technique of simultaneous videolaryngoscopy with flexible bronchoscopy in children with difficult direct laryngoscopy in the Pediatric Difficult Intubation Registry.

Children with difficult tracheal intubation are at increased risk of severe complications, including hypoxaemia and cardiac arrest. Increasing experience with the simultaneous use of videolaryngoscopy and flexible bronchoscopy (hybrid) in adults led us to hypothesise that this hybrid technique could be used safely and effectively in children under general anaesthesia. We reviewed observational data from the international Pediatric Difficult Intubation Registry from 2017 to 2021 to assess the safety and efficacy of hybrid tracheal intubation approaches in paediatric patients.

Predicting primary cesarean delivery in pregnancies complicated by gestational diabetes mellitus.

Background: Prediction models have shown promise in helping clinicians and patients engage in shared decision-making by providing quantitative estimates of individual risk of important clinical outcomes. Gestational diabetes mellitus is a common complication of pregnancy, which places patients at higher risk of primary CD. Suspected fetal macrosomia diagnosed on prenatal ultrasound is a well-known risk factor for primary CD in patients with gestational diabetes mellitus, but tools incorporating multiple risk factors to provide more accurate CD risk are lacking.

Overview of Efforts to Increase Women Enrollment in the Veterans Affairs Million Veteran Program.

Background: Ensuring enhanced delivery of care to women Veterans is a top Veterans Affairs (VA) priority; however, women are historically underrepresented in research that informs evidence-based health care. A primary barrier to women's participation is the inability to engage with research in person due to a number of documented challenges. The VA Million Veteran Program (MVP) is committed to increasing access for women Veterans to participate in research, thereby better understanding conditions specific to this population and how disease manifests differently in women compared to men.

Heme: The Lord of the Iron Ring.

Heme is an iron-protoporphyrin complex with an essential physiologic function for all cells, especially for those in which heme is a key prosthetic group of proteins such as hemoglobin, myoglobin, and cytochromes of the mitochondria. However, it is also known that heme can participate in pro-oxidant and pro-inflammatory responses, leading to cytotoxicity in various tissues and organs such as the kidney, brain, heart, liver, and in immune cells. Indeed, heme, released as a result of tissue damage, can stimulate local and remote inflammatory reactions.

Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes: The GRADE Randomized Clinical Trial.

Importance: Type 2 diabetes (T2D) is the leading cause of kidney disease in the US. It is not known whether glucose-lowering medications differentially affect kidney function.

Objective: To evaluate kidney outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) trial comparing 4 classes of glucose-lowering medications added to metformin for glycemic management in individuals with T2D.

Mental Health Stigma Among Spanish-Speaking Latinos in Baltimore, Maryland.

To assess mental health-related stigma in an emerging Latino immigrant community and explore demographic characteristics associated with stigma. We surveyed 367 Spanish-speaking Latino adults recruited at community-based venues in Baltimore, Maryland. The survey included sociodemographic questions, the Depression Knowledge Measure, Personal Stigma Scale, and the Stigma Concerns about Mental Health Care (SCMHC) assessment.

Higher burden of cardiometabolic and socioeconomic risk factors in women with type 2 diabetes: an analysis of the Glycemic Reduction Approaches in Diabetes (GRADE) baseline cohort.

Introduction: Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

Research Design And Methods: GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline.

Difficult or impossible facemask ventilation in children with difficult tracheal intubation: a retrospective analysis of the PeDI registry.

Background: Difficult facemask ventilation is perilous in children whose tracheas are difficult to intubate. We hypothesised that certain physical characteristics and anaesthetic factors are associated with difficult mask ventilation in paediatric patients who also had difficult tracheal intubation.

Methods: We queried a multicentre registry for children who experienced "difficult" or "impossible" facemask ventilation.

Reductions in Depression and Anxiety Among Autistic Adults Participating in an Intervention to Promote Healthy Relationships.

Importance: Some autistic adults experience depression and anxiety related to their social relationships. There is a need for evidence-based occupational therapy interventions that decrease depression and anxiety and improve the health of social relationships for autistic adults.

Objective: To determine the feasibility and preliminary effectiveness of the Healthy Relationships on the Autism Spectrum (HEARTS) intervention, a six-session, group-based psychoeducational intervention for the improvement of relationship health.

Analysis of the Phase III ENGOT-OV16/NOVA Study: Niraparib Efficacy in Germline Wild-type Recurrent Ovarian Cancer with Homologous Recombination Repair Defects.

Unlabelled: In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline -mutated (non-gm) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-gm cohort. Niraparib demonstrated PFS benefit in patients with either somatic mutated (sm; HR, 0.

Effective contact tracing for COVID-19: A systematic review.

Contact tracing is commonly recommended to control outbreaks of COVID-19, but its effectiveness is unclear. Following PRISMA guidelines, we searched four databases using a range of terms related to contact tracing effectiveness for COVID-19. We found 343 papers; 32 were included.

Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial.

Background: Despite the introduction of new monoclonal antibodies and oral therapies for the treatment of ulcerative colitis, clinical remission rates remain low, underscoring the need for innovative treatment approaches. We assessed whether guselkumab plus golimumab combination therapy was more effective for ulcerative colitis than either monotherapy.

Methods: We did a randomised, double-blind, controlled, proof-of-concept trial at 54 hospitals, academic medical centres, or private practices in nine countries.

Predictors of symptom severity and change among youth in trauma-informed residential care.

Background: Trauma-informed residential care is an intensive intervention setting for youth, but research on its effectiveness is limited and yields mixed findings.

Objectives: The study aims were to; 1) evaluate change over time of mental health (MH) symptoms over 21 months of trauma-informed residential care, and 2) examine the influence of demographic and risk factor variables (e.g.

Shifts in predator behaviour following climate induced disturbance on coral reefs.

Coral reefs are increasingly ecologically destabilized across the globe due to climate change. Behavioural plasticity in corallivore behaviour and short-term trophic ecology in response to bleaching events may influence the extent and severity of coral bleaching and subsequent recovery potential, yet our understanding of these interactions remains unclear. Here, we investigated interactions between corallivory and coral bleaching during a severe high thermal event (10.