Designing an intervention to improve cognitive evaluations in primary care.

Background: Early diagnosis is crucial to the optimal management of patients with cognitive impairment due to Alzheimer's disease (AD) or AD-related dementias. For some patients, early detection of cognitive impairment enables access to disease-modifying therapies. For all patients, it allows access to psychosocial supports.

A large reverse-genetic screen identifies numerous regulators of testis nascent myotube collective cell migration and collective organ sculpting.

Collective cell migration is critical for morphogenesis, homeostasis, and wound healing. Migrating mesenchymal cells form tissues that shape the body's organs. We developed a powerful model, exploring how nascent myotubes migrate onto the testis during pupal development, forming the muscles ensheathing it and creating its characteristic spiral shape.

Proximity proteomics provides a new resource for exploring the function of Afadin and the complexity of cell-cell adherens junctions.

The network of proteins at the interface between cell-cell adherens junctions and the actomyosin cytoskeleton provides robust yet dynamic connections that facilitate cell shape change and motility. While this was initially thought to be a simple linear connection via classic cadherins and their associated catenins, we now have come to appreciate that many more proteins are involved, providing robustness and mechanosensitivity. Defining the full network of proteins in this network remains a key objective in our field.

Tumor architecture and emergence of strong genetic alterations are bottlenecks for clonal evolution in primary prostate cancer.

Prostate cancer (PCA) exhibits high levels of intratumoral heterogeneity. In this study, we developed a mathematical model to study the growth and genetic evolution of PCA. We explored the possible evolutionary patterns and demonstrated that tumor architecture represents a major bottleneck for divergent clonal evolution.

Active Choice Nudge to Increase Screening for Primary Aldosteronism in At-Risk Patients.

Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension, yet screening remains startlingly infrequent. We describe (1) PA screening practices in a large, diverse health system, (2) the development of a computable phenotype for PA screening, and (3) the design and pilot deployment of an electronic health record (EHR)-based active choice nudge to recommend PA screening.

Study Design: A multidisciplinary team developed a multipronged intervention to improve PA screening informed by guidelines, expertise, and multivariable analyses of factors associated with screening.

40 years since the Heidelberg genetic screen that revolutionized developmental and cell biology.

Our current understanding of the molecular basis of embryonic development and the shared machinery underlying this remarkable process has its roots in three papers published 40 years ago, which summarize the results of the Nobel Prize-winning 'Heidelberg screen'. The genesis of these experiments that empowered us and the stories behind the experiments are worth revisiting.

A large reverse-genetic screen identifies numerous regulators of testis nascent myotube collective cell migration and collective organ sculpting.

Collective cell migration is critical for morphogenesis, homeostasis, and wound healing. During development migrating mesenchymal cells form tissues that shape some of the body's organs. We have developed a powerful model for examining this, exploring how Drosophila testis nascent myotubes migrate onto the testis during pupal development, forming the muscles that ensheath it and also creating its characteristic spiral shape.

Plexin/Semaphorin Antagonism Orchestrates Collective Cell Migration, Gap Closure and Organ sculpting by Contact-Mesenchymalization.

Cell behavior emerges from the intracellular distribution of properties like protrusion, contractility and adhesion. Thus, characteristic emergent rules of collective migration can arise from cell-cell contacts locally tweaking architecture - orchestrating self-regulation during development, wound healing, and cancer progression. The new testis-nascent-myotube-system allows dissection of contact-dependent migration in vivo at high resolution.

Telemedicine and Access to Elective Cholecystectomy for Socially Vulnerable Adults: A Pilot Randomized Clinical Trial.

Importance: Socially vulnerable patients with symptomatic cholelithiasis are more likely to face barriers to accessing surgical care. This barrier to access can lead to delays in treatment, the need for emergent cholecystectomy, and worse outcomes.

Objectives: To determine the effectiveness of telemedicine vs in-person surgical consultation on access to elective cholecystectomy in socially vulnerable populations and to evaluate the association of scheduling navigation with access to elective cholecystectomy in these populations.

Emergence of cellular nematic order is a conserved feature of gastrulation in animal embryos.

Cells undergo dramatic changes in morphology during embryogenesis, yet how these changes affect the formation of ordered tissues remains elusive. Here we find that the emergence of a nematic liquid crystal phase occurs in cells during gastrulation in the development of embryos of fish, frogs, and fruit flies. Moreover, the spatial correlations in all three organisms are long-ranged and follow a similar power-law decay with less than unity for the nematic order parameter, suggesting a common underlying physical mechanism unifies events in these distantly related species.

Behavioral Interventions to Improve Breast Cancer Screening Outreach: Two Randomized Clinical Trials.

Importance: Despite public health efforts, breast cancer screening rates remain below national goals.

Objective: To evaluate whether bulk ordering, text messaging, and clinician endorsement increase breast cancer screening rates.

Design, Setting, And Participants: Two concurrent, pragmatic, randomized clinical trials, each with a 2-by-2 factorial design, were conducted between October 25, 2021, and April 25, 2022, in 2 primary care regions of an academic health system.

Germline homozygosity and allelic imbalance of HLA-I are common in esophagogastric adenocarcinoma and impair the repertoire of immunogenic peptides.

Background: The individual HLA-I genotype is associated with cancer, autoimmune diseases and infections. This study elucidates the role of germline homozygosity or allelic imbalance of HLA-I loci in esophago-gastric adenocarcinoma (EGA) and determines the resulting repertoires of potentially immunogenic peptides.

Methods: HLA genotypes and sequences of either (1) 10 relevant tumor-associated antigens (TAAs) or (2) patient-specific mutation-associated neoantigens (MANAs) were used to predict good-affinity binders using an in silico approach for MHC-binding (www.

Evolutionary trajectories of small cell lung cancer under therapy.

The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown. Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity.

Moonwalking molecular machines: Unraveling the choreography of myosin filament assembly.

We have made tremendous progress in identifying the machines that shape the architecture of actin filaments. However, we know less about the mechanisms mediating myosin assembly at the supramolecular level. In this issue, Quintanilla et al.

Adenylosuccinate lyase deficiency affects neurobehavior via perturbations to tyramine signaling in Caenorhabditis elegans.

Adenylosuccinate lyase deficiency is an ultrarare congenital metabolic disorder associated with muscle weakness and neurobehavioral dysfunction. Adenylosuccinate lyase is required for de novo purine biosynthesis, acting twice in the pathway at non-sequential steps. Genetic models can contribute to our understanding of the etiology of disease phenotypes and pave the way for development of therapeutic treatments.

Somatic rearrangements causing oncogenic ectodomain deletions of FGFR1 in squamous cell lung cancer.

The discovery of frequent 8p11-p12 amplifications in squamous cell lung cancer (SQLC) has fueled hopes that FGFR1, located inside this amplicon, might be a therapeutic target. In a clinical trial, only 11% of patients with 8p11 amplification (detected by FISH) responded to FGFR kinase inhibitor treatment. To understand the mechanism of FGFR1 dependency, we performed deep genomic characterization of 52 SQLCs with 8p11-p12 amplification, including 10 tumors obtained from patients who had been treated with FGFR inhibitors.

Exploring the evolution and function of Canoe's intrinsically disordered region in linking cell-cell junctions to the cytoskeleton during embryonic morphogenesis.

One central question for cell and developmental biologists is defining how epithelial cells can change shape and move during embryonic development without tearing tissues apart. This requires robust yet dynamic connections of cells to one another, via the cell-cell adherens junction, and of junctions to the actin and myosin cytoskeleton, which generates force. The last decade revealed that these connections involve a multivalent network of proteins, rather than a simple linear pathway.

Reconstructing Phylogenetic Relationship in Bladder Cancer: A Methodological Overview.

Bladder cancer (BC) expresses itself as a highly heterogeneous disease both at the histological and molecular level, often occurring as synchronous or metachronous multifocal disease with high risk of recurrence and potential to metastasize. Multiple sequencing studies focusing on both non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) gave insights into the extent of both inter- and intrapatient heterogeneity, but many questions on clonal evolution in BC remain unanswered. In this review article, we provide an overview over the technical and theoretical concepts linked to reconstructing evolutionary trajectories in BC and propose a set of tools and established software for phylogenetic analysis.