Long-Term Impact of a Medical School Course on the Intersection of Art and Medical History.

Background: One recent trend in medical education is the integration of humanities into the curriculum, including viewing works of art in museums, with analysis of short-term, but not long-term, impact. We developed a course for medical students, trainees, and faculty at the Icahn School of Medicine at Mount Sinai co-taught by an art historian and a physician/medical historian that features images of great works of art to make connections between art and medical history with the following goals: 1. To encourage the students to make careful and systematic observations, describe what they see to others in the group, and exchange their views respectfully, 2.

Automated multi-scale computational pathotyping (AMSCP) of inflamed synovial tissue.

Rheumatoid arthritis (RA) is a complex immune-mediated inflammatory disorder in which patients suffer from inflammatory-erosive arthritis. Recent advances on histopathology heterogeneity of RA synovial tissue revealed three distinct phenotypes based on cellular composition (pauci-immune, diffuse and lymphoid), suggesting that distinct etiologies warrant specific targeted therapy which motivates a need for cost effective phenotyping tools in preclinical and clinical settings. To this end, we developed an automated multi-scale computational pathotyping (AMSCP) pipeline for both human and mouse synovial tissue with two distinct components that can be leveraged together or independently: (1) segmentation of different tissue types to characterize tissue-level changes, and (2) cell type classification within each tissue compartment that assesses change across disease states.

Pronounced early differentiation underlies zebra finch gonadal germ cell development.

The diversity of germ cell developmental strategies has been well documented across many vertebrate clades. However, much of our understanding of avian primordial germ cell (PGC) specification and differentiation has derived from only one species, the chicken (Gallus gallus). Of the three major classes of birds, chickens belong to Galloanserae, representing less than 4% of species, while nearly 95% of extant bird species belong to Neoaves.

Measurement of Energy Correlators inside Jets and Determination of the Strong Coupling α_{S}(m_{Z}).

Energy correlators that describe energy-weighted distances between two or three particles in a hadronic jet are measured using an event sample of sqrt[s]=13  TeV proton-proton collisions collected by the CMS experiment and corresponding to an integrated luminosity of 36.3  fb^{-1}. The measured distributions are consistent with the trends in the simulation that reveal two key features of the strong interaction: confinement and asymptotic freedom.

Distinct patterns of genetic variation at low-recombining genomic regions represent haplotype structure.

Genomic regions sometimes show patterns of genetic variation distinct from the genome-wide population structure. Such deviations have often been interpreted to represent effects of selection. However, systematic investigation of whether and how non-selective factors, such as recombination rates, can affect distinct patterns has been limited.

Placenta-Mediated Conditions: Past, Present, and Future Perspectives.

Pregnancy is a highly regulated biological condition in which a successful outcome is heavily dependent on maintaining a delicate balance through maternal-fetal dialog at various levels [...

Tuberculosis in otherwise healthy adults with inherited TNF deficiency.

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses.

Mosaic sarbecovirus nanoparticles elicit cross-reactive responses in pre-vaccinated animals.

Immunization with mosaic-8b (nanoparticles presenting 8 SARS-like betacoronavirus [sarbecovirus] receptor-binding domains [RBDs]) elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated the effects of prior COVID-19 vaccinations in non-human primates and mice on anti-sarbecovirus responses elicited by mosaic-8b, admix-8b (8 homotypics), or homotypic SARS-CoV-2 immunizations, finding the greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate mapping, in which antibodies from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting.

Engineering acyclovir-induced RNA nanodevices for reversible and tunable control of aptamer function.

Small molecule-regulated RNA devices have the potential to modulate diverse aspects of cellular function, but the small molecules used to date have potential toxicities limiting their use in cells. Here we describe a method for creating drug-regulated RNA nanodevices (RNs) using acyclovir, a biologically compatible small molecule with minimal toxicity. Our modular approach involves a scaffold comprising a central F30 three-way junction, an integrated acyclovir aptamer on the input arm, and a variable effector-binding aptamer on the output arm.

An Introduction to the Crossover Trial Design.

Editor's note: This is the 23rd article in a series on clinical research by nurses. The series is designed to be used as a resource for nurses to understand the concepts and principles essential to research. Each column will present the concepts that underpin evidence-based practice-from research design to data interpretation.

Measurement of multijet azimuthal correlations and determination of the strong coupling in proton-proton collisions at .

A measurement is presented of a ratio observable that provides a measure of the azimuthal correlations among jets with large transverse momentum . This observable is measured in multijet events over the range of - based on data collected by the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 , corresponding to an integrated luminosity of 134 . The results are compared with predictions from Monte Carlo parton-shower event generator simulations, as well as with fixed-order perturbative quantum chromodynamics (pQCD) predictions at next-to-leading-order (NLO) accuracy obtained with different parton distribution functions (PDFs) and corrected for nonperturbative and electroweak effects.

Myosin forces elicit an F-actin structural landscape that mediates mechanosensitive protein recognition.

Cells mechanically interface with their surroundings through cytoskeleton-linked adhesions, allowing them to sense physical cues that instruct development and drive diseases such as cancer. Contractile forces generated by myosin motor proteins mediate these mechanical signal transduction processes through unclear protein structural mechanisms. Here, we show that myosin forces elicit structural changes in actin filaments (F-actin) that modulate binding by the mechanosensitive adhesion protein α-catenin.

Opto-CLIP reveals dynamic FMRP regulation of mRNAs upon CA1 neuronal activation.

Neuronal diversity and function are intricately linked to the dynamic regulation of RNA metabolism, including splicing, localization, and translation. Electrophysiologic studies of synaptic plasticity, models for learning and memory, are disrupted in Fragile X Syndrome (FXS). FXS is characterized by the loss of FMRP, an RNA-binding protein (RBP) known to bind and suppress translation of specific neuronal RNAs.

Interferon Gamma in Sickness Predisposing to Infectious Diseases.

In recent decades, the prevalence of inborn errors of immunity has increased, necessitating the development of more effective treatment and care options for these highly morbid conditions. Due to these “experiments of nature,” the complicated nature of the immune system is being revealed. Based on the functional and molecular tests, targeted therapies are now being developed which offer a more effective approach and reduce damage.

The Fanconi anemia pathway induces chromothripsis and ecDNA-driven cancer drug resistance.

Chromothripsis describes the catastrophic shattering of mis-segregated chromosomes trapped within micronuclei. Although micronuclei accumulate DNA double-strand breaks and replication defects throughout interphase, how chromosomes undergo shattering remains unresolved. Using CRISPR-Cas9 screens, we identify a non-canonical role of the Fanconi anemia (FA) pathway as a driver of chromothripsis.

CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes.

Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause immunodeficiency, centromeric instability, and facial anomalies syndrome, characterized by DNA hypomethylation at heterochromatin. It remains unclear why CDCA7-HELLS is the sole nucleosome remodeling complex whose deficiency abrogates the maintenance of DNA methylation. We here identify the unique zinc-finger domain of CDCA7 as an evolutionarily conserved hemimethylation-sensing zinc finger (HMZF) domain.

Safety and efficacy of anticoagulant treatment in patients with ovarian vein thrombosis: a systematic review and meta-analysis of observational studies.

Background: The role of anticoagulation in ovarian vein thrombosis (OVT) is uncertain.

Objectives: We aimed to evaluate safety and efficacy of anticoagulant treatment in OVT patients.

Methods: A systematic search was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases up to April 2024.

Stem cells tightly regulate dead cell clearance to maintain tissue fitness.

Billions of cells are eliminated daily from our bodies. Although macrophages and dendritic cells are dedicated to migrating and engulfing dying cells and debris, many epithelial and mesenchymal tissue cells can digest nearby apoptotic corpses. How these non-motile, non-professional phagocytes sense and eliminate dying cells while maintaining their normal tissue functions is unclear.

Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent Lu-Labeled Radiohapten.

Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic γ- and β-emitting isotope Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Gemini was synthesized by linking 2 -2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker.

WENDY: Covariance dynamics based gene regulatory network inference.

Determining gene regulatory network (GRN) structure is a central problem in biology, with a variety of inference methods available for different types of data. For a widely prevalent and challenging use case, namely single-cell gene expression data measured after intervention at multiple time points with unknown joint distributions, there is only one known specifically developed method, which does not fully utilize the rich information contained in this data type. We develop an inference method for the GRN in this case, netWork infErence by covariaNce DYnamics, dubbed WENDY.

Differential dynamics specify MeCP2 function at nucleosomes and methylated DNA.

Methyl-CpG-binding protein 2 (MeCP2) is an essential chromatin-binding protein whose mutations cause Rett syndrome (RTT), a severe neurological disorder that primarily affects young females. The canonical view of MeCP2 as a DNA methylation-dependent transcriptional repressor has proven insufficient to describe its dynamic interaction with chromatin and multifaceted roles in genome organization and gene expression. Here we used single-molecule correlative force and fluorescence microscopy to directly visualize the dynamics of wild-type and RTT-causing mutant MeCP2 on DNA.

Widespread cultural change in declining populations of Amazon parrots.

Species worldwide are experiencing anthropogenic environmental change, and the long-term impacts on animal cultural traditions such as vocal dialects are often unknown. Our prior studies of the yellow-naped amazon () revealed stable vocal dialects over an 11-year period (1994-2005), with modest shifts in geographic boundaries and acoustic structure of contact calls. Here, we examined whether yellow-naped amazons maintained stable dialects over the subsequent 11-year time span from 2005 to 2016, culminating in 22 years of study.