The path forward for large language models in medicine is open.

Large language models (LLMs) are increasingly applied in medical documentation and have been proposed for clinical decision support. We argue that the future for LLMs in medicine must be based on transparent and controllable open-source models. Openness enables medical tool developers to control the safety and quality of underlying AI models, while also allowing healthcare professionals to hold these models accountable.

Safety of dostarlimab in combination with chemotherapy in patients with primary advanced or recurrent endometrial cancer in a phase III, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY).

Background: In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.

Objectives: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.

Patient-reported outcomes of adverse events after COVID-19 vaccination in Nigeria: A mixed methods study.

Background: Adverse events following immunization (AEFIs), especially if serious, may impact vaccine recipients' quality of life and financial well-being and fuel vaccine hesitancy. Nigeria rolled out COVID-19 vaccination in 2021 with little known about the impact of AEFIs on an individual's quality of life. No study in Africa has explored the health and financial impact of AEFIs.

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.

Background: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.

Methods: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care.

The Newfoundland and Labrador mosaic founder population descends from an Irish and British diaspora from 300 years ago.

The founder population of Newfoundland and Labrador (NL) is a unique genetic resource, in part due to its geographic and cultural isolation, where historical records describe a migration of European settlers, primarily from Ireland and England, to NL in the 18th and 19th centuries. Whilst its historical isolation, and increased prevalence of certain monogenic disorders are well appreciated, details of the fine-scale genetic structure and ancestry of the population are lacking. Understanding the genetic origins and background of functional, disease causing, genetic variants would aid genetic mapping efforts in the Province.

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer.

Background: Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer.

Methods: We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial.

Packaging cells for lentiviral vectors generated using the cumate and coumermycin gene induction systems and nanowell single-cell cloning.

Lentiviral vectors (LVs) are important for cell therapy because of their capacity to stably modify the genome after integration. This study describes a novel and relatively simple approach to generate packaging cells and producer clones for self-inactivating (SIN) LVs pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G). A novel gene regulation system, based on the combination of the cumate and coumermycin induction systems, was developed to ensure tight control for the expression of cytotoxic packaging elements.

Right Ventricular Architectural Remodeling and Functional Adaptation in Pulmonary Hypertension.

Background: Global indices of right ventricle (RV) function provide limited insights into mechanisms underlying RV remodeling in pulmonary hypertension (PH). While RV myocardial architectural remodeling has been observed in PH, its effect on RV adaptation is poorly understood.

Methods: Hemodynamic assessments were performed in 2 rodent models of PH.

Machine Learning for Workflow Applications in Screening Mammography: Systematic Review and Meta-Analysis.

Background Advances in computer processing and improvements in data availability have led to the development of machine learning (ML) techniques for mammographic imaging. Purpose To evaluate the reported performance of stand-alone ML applications for screening mammography workflow. Materials and Methods Ovid Embase, Ovid Medline, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science literature databases were searched for relevant studies published from January 2012 to September 2020.

Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase.

Background: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase.

Federated learning for predicting clinical outcomes in patients with COVID-19.

Federated learning (FL) is a method used for training artificial intelligence models with data from multiple sources while maintaining data anonymity, thus removing many barriers to data sharing. Here we used data from 20 institutes across the globe to train a FL model, called EXAM (electronic medical record (EMR) chest X-ray AI model), that predicts the future oxygen requirements of symptomatic patients with COVID-19 using inputs of vital signs, laboratory data and chest X-rays. EXAM achieved an average area under the curve (AUC) >0.

Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

Background: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied.

Methods: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.

Alagille Syndrome: A Focused Review on Clinical Features, Genetics, and Treatment.

Alagille syndrome (ALGS) is an autosomal dominant disorder caused by pathogenic variants in or , which encode fundamental components of the Notch signaling pathway. Clinical features span multiple organ systems including hepatic, cardiac, vascular, renal, skeletal, craniofacial, and ocular, and occur with variable phenotypic penetrance. Genotype-phenotype correlation studies have not yet shown associations between mutation type and clinical manifestations or severity, and it has been hypothesized that modifier genes may modulate the effects of and pathogenic variants.

Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.

Background: Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear.

Methods: We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total.

Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant.

Background: Assessment of the safety and efficacy of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants of concern, including the B.1.351 (501Y.

Federated Learning used for predicting outcomes in SARS-COV-2 patients.

'Federated Learning' (FL) is a method to train Artificial Intelligence (AI) models with data from multiple sources while maintaining anonymity of the data thus removing many barriers to data sharing. During the SARS-COV-2 pandemic, 20 institutes collaborated on a healthcare FL study to predict future oxygen requirements of infected patients using inputs of vital signs, laboratory data, and chest x-rays, constituting the "EXAM" (EMR CXR AI Model) model. EXAM achieved an average Area Under the Curve (AUC) of over 0.

Depression and Nicotine Withdrawal Associations with Combustible and Electronic Cigarette Use.

Depression is a risk factor for nicotine use and withdrawal. Population level epidemiologic studies that include users of either combustible or electronic cigarette (NICUSER) could inform interventions to reduce nicotine dependence in vulnerable populations. The current study examined the relationship between depression diagnosis (DEPDX), NICUSER, and lifetime rates of DSM-V nicotine withdrawal (NW) symptoms in a nationally representative sample of US adults ( = 979), who answered related questions in surveys administered through GfK's KnowledgePanel.

Hyperpolarized C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer.

Purpose: To compare hyperpolarized carbon 13 (C) MRI with dynamic contrast material-enhanced (DCE) MRI in the detection of early treatment response in breast cancer.

Materials And Methods: In this institutional review board-approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent C MRI after injection of hyperpolarized [1-carbon 13 {C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The C-labeled lactate-to-pyruvate ratio derived from hyperpolarized C MRI and the pharmacokinetic parameters transfer constant ( ) and washout parameter ( ) derived from DCE MRI were compared before and after treatment.

Osteoarthritis physical activity care pathway (OA-PCP): results of a feasibility trial.

Background: To obtain information on feasibility and acceptability, as well as preliminary data on efficacy, of an Osteoarthritis Physical activity Care Pathway (OA-PCP).

Methods: This was a single group pilot study involving 60 participants with symptomatic, physician diagnosed knee or hip OA, recruited from primary care clinics. Participants self-reported completing less than 150 min per week of moderate-to-vigorous physical activity (MVPA) at baseline.

Functional arrays of human pluripotent stem cell-derived cardiac microtissues.

To accelerate the cardiac drug discovery pipeline, we set out to develop a platform that would be capable of quantifying tissue-level functions such as contractile force and be amenable to standard multiwell-plate manipulations. We report a 96-well-based array of 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues - termed Cardiac MicroRings (CaMiRi) - in custom 3D-print-molded multiwell plates capable of contractile force measurement. Within each well, two elastomeric microcantilevers are situated above a circumferential ramp.

Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition.

Visceral leishmaniasis (VL), caused by the protozoan parasites and , is one of the major parasitic diseases worldwide. There is an urgent need for new drugs to treat VL, because current therapies are unfit for purpose in a resource-poor setting. Here, we describe the development of a preclinical drug candidate, GSK3494245/DDD01305143/compound 8, with potential to treat this neglected tropical disease.

Cell engineering with microfluidic squeezing preserves functionality of primary immune cells in vivo.

The translational potential of cell-based therapies is often limited by complications related to effectively engineering and manufacturing functional cells. While the use of electroporation is widespread, the impact of electroporation on cell state and function has yet to be fully characterized. Here, we use a genome-wide approach to study optimized electroporation treatment and identify striking disruptions in the expression profiles of key functional transcripts of human T cells.

Safety and efficacy of novel malaria vaccine regimens of RTS,S/AS01B alone, or with concomitant ChAd63-MVA-vectored vaccines expressing ME-TRAP.

We assessed a combination multi-stage malaria vaccine schedule in which RTS,S/AS01B was given concomitantly with viral vectors expressing multiple-epitope thrombospondin-related adhesion protein (ME-TRAP) in a 0-month, 1-month, and 2-month schedule. RTS,S/AS01B was given as either three full doses or with a fractional (1/5th) third dose. Efficacy was assessed by controlled human malaria infection (CHMI).