Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer.

Immunotherapy options for immune cold tumors, like prostate cancer, are limited. We show that AR downregulates MHCI expression/antigen presentation and that AR inhibition improves T-cell responses and tumor control. This suggests that treatments combining AR inhibitors and checkpoint blockade may improve tumor immune surveillance and antitumor immunity in patients.

Molecular Tumor Board for Unicorns: Outcomes for rare and ultra-rare cancers using an N-of-One personalized treatment strategy.

Treatment of rare/ultra-rare tumors is an unmet need due to a lack of standardized therapies and clinical trials. We developed the Molecular Tumor Board (MTB), a multidisciplinary team that integrates molecular profiling to generate personalized, N-of-One treatments for advanced cancers. This study evaluates 112 patients with rare/ultra-rare tumors who presented to the MTB and were evaluable for clinical therapeutic outcome.

A cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming.

A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health.

Antibodies to and species in serum and synovial fluid from people with rheumatic diseases.

Unlabelled: Vector-borne infections may underlie some rheumatic diseases, particularly in people with joint effusions. This study aimed to compare serum and synovial fluid antibodies to and spp. in patients with rheumatic diseases.

Connecting single-cell transcriptomes to projectomes in mouse visual cortex.

The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitions that include multiple cellular properties can offer additional insights into a neuron's role in brain circuits. While the Patch-seq method can investigate how transcriptomic properties relate to the local morphological and electrophysiological properties of cell types, linking transcriptomic identities to long-range projections is a major unresolved challenge.

Active compensation for changes in TDH3 expression mediated by direct regulators of TDH3 in Saccharomyces cerevisiae.

Genetic networks are surprisingly robust to perturbations caused by new mutations. This robustness is conferred in part by compensation for loss of a gene's activity by genes with overlapping functions, such as paralogs. Compensation occurs passively when the normal activity of one paralog can compensate for the loss of the other, or actively when a change in one paralog's expression, localization, or activity is required to compensate for loss of the other.

Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex.

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1.

The projection-specific signals that establish functionally segregated dopaminergic synapses.

Dopaminergic projections regulate various brain functions and are implicated in many neuropsychiatric disorders. There are two anatomically and functionally distinct dopaminergic projections connecting the midbrain to striatum: nigrostriatal, which controls movement, and mesolimbic, which regulates motivation. However, how these discrete dopaminergic synaptic connections are established is unknown.

'It feels like I'm back to being a teacher': A longitudinal trajectory analysis of teachers' experiences during the first 8 months of COVID-19 in England.

Background: Understanding teachers' experiences throughout the school closures and reopenings that have characterized large periods of the COVID-19 pandemic provides us with unique insights into what it means to be a teacher during a global public health crisis.

Aim And Method: To investigate teachers' narratives of their experiences, we conducted 95 semi-structured interviews with 24 teachers in England across four time points between April and November 2020. We used a longitudinal qualitative trajectory analysis of participants' stories of their high-, low- and turning-points.

The association of host and vector characteristics with pathogen and endosymbiont infection.

Surveillance of the fleas and flea-borne pathogens infecting cats is important for both human and animal health. Multiple zoonotic and species are known to infect the most common flea infesting cats and dogs worldwide: , the cat flea. The ability of other flea species to transmit pathogens is relatively unexplored.

Adapting Family Planning Service Delivery in Title X and School-Based Settings during COVID-19: Provider and Staff Experiences.

The COVID-19 pandemic introduced urgent and unique challenges to family planning providers and staff in ensuring continued access to high-quality services, particularly for groups who experience greater barriers to accessing services, such as women with systemically marginalized identities and adolescents and young adults (AYA). While research has documented key adaptations made to service delivery during the early phase of the pandemic, limited studies have used qualitative methods. This paper draws on qualitative interview data from family planning providers and staff in Title-X-funded clinics and school-based clinics-two settings that serve populations that experience greater barriers to accessing care-to (a) describe the adaptations made to service delivery during the first year of the pandemic and (b) explore provider and staff experiences and impressions implementing these adaptations.

Eosinophilic Myocarditis Presenting as Cardiac Tamponade: A Diagnostic Challenge.

Unlabelled: Eosinophilic myocarditis (EM) is a rare cause of acute heart failure. It can occur secondary to drug hypersensitivity, autoimmune diseases such as vasculitis, idiopathic hypereosinophilic syndrome (HES) or malignancy, but is often under-recognized and underdiagnosed, being confused with other causes of heart failure. While EM is associated with various clinical symptoms, it is rarely associated with cardiac tamponade that requires urgent pericardiocentesis.

Women's experiences with person-centered family planning care: Differences by sociodemographic characteristics.

Objective: Person-centered contraceptive care is associated with positive reproductive health outcomes. Our objective was to analyze patients' ratings on the newly developed Person-Centered Contraceptive Counseling scale (PCCC) to provide distributions for a nationally representative population and to assess differences by sociodemographic characteristics.

Study Design: Using data from 2017 to 2019 National Survey of Family Growth (NSFG), we analyzed ratings across the four PCCC items among 2242 women who received contraceptive counseling in the past year.

Sustained Oncogenic Signaling in the Cytostatic State Enables Targeting of Nonproliferating Persistent Cancer Cells.

Unlabelled: Many advanced therapeutics possess cytostatic properties that suppress cancer cell growth without directly inducing death. Treatment-induced cytostatic cancer cells can persist and constitute a reservoir from which recurrent growth and resistant clones can develop. Current management approaches primarily comprise maintenance and monitoring because strategies for targeting nonproliferating cancer cells have been elusive.

Hypertensive events after the initiation of contemporary cancer therapies for breast cancer control.

Background: Contemporary therapies improve breast cancer (BC) outcomes. Yet, many of these therapies have been increasingly linked with serious cardiotoxicity, including reports of profound hypertension. Yet, the incidence, predictors, and impacts of these events are largely unknown.

A Unified Protocol to Streamline Molecular and Cellular Analysis for Three-Dimensional Cell Cultures.

Three-dimensional (3D) cell cultures based on reconstituted basement membrane materials recapitulate features of extracellular matrix (ECM) and tissue stiffness in vivo and provide a physiologically relevant platform to study complex cellular processes, such as stem cell differentiation and tissue morphogenesis, that are otherwise difficult in animal models. The form and composition of 3D matrices in culture can interfere with and pose challenges for different experimental setups and assays, which necessitate alterations to facilitate analysis. Here, we provide a unified protocol for 3D cell cultures with modular workflows that streamline procedures for compatibility with common molecular and cellular assays such as live-cell imaging, immunofluorescence , qPCR, RNAseq, western blotting, and quantitative mass spectrometry.

Serial changes in liquid biopsy-derived variant allele frequency predict immune checkpoint inhibitor responsiveness in the pan-cancer setting.

Major immunotherapy challenges include a limited number of predictive biomarkers and the unusual imaging features post-therapy, such as pseudo-progression, which denote immune infiltrate-mediated tumor enlargement. Such phenomena confound clinical decision-making, since the cancer may eventually regress, and the patient should stay on treatment. We prospectively evaluated serial, blood-derived cell-free DNA (cfDNA) (baseline and 2-3 weeks post-immune checkpoint inhibitors [ICIs]) for variant allele frequency (VAF) and blood tumor mutation burden (bTMB) changes (next-generation sequencing) (N = 84 evaluable patients, diverse cancers).

Local connectivity and synaptic dynamics in mouse and human neocortex.

We present a unique, extensive, and open synaptic physiology analysis platform and dataset. Through its application, we reveal principles that relate cell type to synaptic properties and intralaminar circuit organization in the mouse and human cortex. The dynamics of excitatory synapses align with the postsynaptic cell subclass, whereas inhibitory synapse dynamics partly align with presynaptic cell subclass but with considerable overlap.

Incorporating Competencies Related to Project Management into the Joint Taskforce Core Competency Framework for Clinical Research Professionals.

In 2014, the Joint Task Force for Clinical Trial Competency (JTF) published its Core Competency Framework. The Framework has been utilized internationally by academic institutions, corporate entities, professional associations, educational and training programs, and regulatory agencies and integrated into their activities. The JTF has continually updated and expanded the scope of the Framework to reflect changes in the scientific understanding and methodology utilized in conducting clinical research.

Acute cardiotoxicity after initiation of the novel tyrosine kinase inhibitor gilteritinib for acute myeloid leukemia.

Background: Gilteritinib is a novel FMS-like tyrosine kinase 3 inhibitor recently approved by the United States Food and Drug Administration in 2018 for relapsed or refractory acute myeloid leukemia. However, gilteritinib may be associated with underrecognized cardiotoxicities.

Case Presentation: This case describes a patient with a history significant for hyperlipidemia who was diagnosed with relapsed acute myeloid leukemia.

Assessing CAR T-Cell Therapy Response Using Genome-Wide Sequencing of Cell-Free DNA in Patients With B-Cell Lymphomas.

Methods that enable monitoring of therapeutic efficacy of autologous chimeric antigen receptor (CAR) T-cell therapy will be clinically useful. The aim of this study is to demonstrate the feasibility of blood-derived cell-free DNA (cfDNA) to predict CAR T-cell therapy response in patients with refractory B-cell lymphomas. Whole blood was collected before and throughout CAR T-cell therapy until day 154.