Jansen metaphyseal chondrodysplasia: analysis of craniofacial manifestations.

Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by constitutive activation of parathyroid hormone type 1 receptor (PTH1R). We sought to characterize the craniofacial phenotype of patients with the disease. Six patients with genetically confirmed JMC underwent comprehensive craniofacial phenotyping revealing a distinct facial appearance that prompted a cephalometric analysis demonstrating a pattern of mandibular retrognathia.

Noncanonical Short-Latency Auditory Pathway Directly Activates Deep Cortical Layers.

Auditory processing in the cerebral cortex is considered to begin with thalamocortical inputs to layer 4 (L4) of the primary auditory cortex (A1). In this canonical model, A1 L4 inputs initiate a hierarchical cascade, with higher-order cortices receiving pre-processed information for the slower integration of complex sounds. Here, we identify alternative ascending pathways in mice that bypass A1 and directly reach multiple layers of the secondary auditory cortex (A2), indicating parallel activation of these areas alongside sequential information processing.

ExerGeneDB: A physical exercise-regulated differential gene expression database.

Background: Exercise induces molecular changes that involve multiple organs and tissues. Moreover, these changes are modulated by various exercise parameters-such as intensity, frequency, mode, and duration-as well as by clinical features like gender, age, and body mass index (BMI), each eliciting distinct biological effects. To assist exercise researchers in understanding these changes from a comprehensive perspective that includes multiple organs, diverse exercise regimens, and a range of clinical features, we developed Exercise Regulated Genes Database (ExerGeneDB), a database of exercise-regulated differential genes.

Skeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes.

Background And Aims: Skeletal muscle (SM) fat infiltration, or intermuscular adipose tissue (IMAT), reflects muscle quality and is associated with inflammation, a key determinant in cardiometabolic disease. Coronary flow reserve (CFR), a marker of coronary microvascular dysfunction (CMD), is independently associated with body mass index (BMI), inflammation and risk of heart failure, myocardial infarction, and death. The relationship between SM quality, CMD, and cardiovascular outcomes is not known.

Challenges Faced by Patients Undergoing Fecal Ostomy Surgery: A Qualitative Study of Colorectal Cancer Patient Perspectives.

Background: Ostomy education and support is instrumental in surgical recovery and adaptation. We aimed to evaluate 1) challenges faced by fecal ostomy patients with colorectal cancer and 2) resources necessary for recovery.

Methods: We recruited patients 21-90 days after scheduled fecal ostomy surgery for locally advanced or metastatic colorectal cancer from a single, tertiary academic center.

A biophysical basis for the spreading behavior and limited diffusion of Xist.

Xist RNA initiates X inactivation as it spreads in cis across the chromosome. Here, we reveal a biophysical basis for its cis-limited diffusion. Xist RNA and HNRNPK together drive a liquid-liquid phase separation (LLPS) that encapsulates the chromosome.

Affective, Behavioral, and Cognitive Symptoms Associated With Focal Impaired Awareness (Complex Partial) Seizures: Evaluation and Treatment.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.

Machine learning to predict periprosthetic joint infections following primary total hip arthroplasty using a national database.

Introduction: Periprosthetic joint infection (PJI) following total hip arthroplasty (THA) remains a devastating complication for patients and surgeons. Given the implications of these infections and the current paucity of risk calculators utilizing machine learning (ML), this study aimed to develop an ML algorithm that could accurately identify risk factors for developing a PJI following primary THA using a national database.

Materials And Methods: A total of 51,053 patients who underwent primary THA between 2013 and 2020 were identified using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database.

Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury.

Background: Presentations and outcomes of acute myocardial infarction (MI) differ between women and men, with the worst outcomes being reported in younger women. Mental stress induced ischemia and sympathetic activation have been suggested to play a prominent role in the pathogenesis of MI in younger women, however, the impact of sex hormones on these parameters remains unknown.

Methods: The effect of sex hormones and age on myocardial infarct size and myocardial sympathetic activity (MSA) was assessed in male and female, as well as young (4-6 months) and aged (20-22 months) FVB/N mice (n = 106, 60 gonadectomized and 46 sham-operated animals) who underwent in vivo [C]meta-hydroxyephedrine ([C]mHED) positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging 24 h after a 30 min myocardial ischemic injury.

EV-idence uncovered: kidney-on-chip study links circulating EVs of cardiorenal syndrome to renal pathology.

The intertwined nature of cardiac and renal failure, where dysfunction in one organ predicts a poor outcome in the other, has long driven the interest in uncovering the exact molecular links between the two. Elucidating the mechanisms driving Cardiorenal Syndrome (CRS) will enable the development of targeted therapies that disrupt this detrimental cycle, potentially improving outcomes for patients. A recent study by Chatterjee .

Dynamic X-ray Microtomography vs. Laser-Doppler Vibrometry: A Comparative Study.

Purpose: There are challenges in understanding the biomechanics of the human middle ear, and established methods for studying this system show significant limitations. In this study, we evaluate a novel dynamic imaging technique based on synchrotron X-ray microtomography designed to assess the biomechanical properties of the human middle ear by comparing it to laser-Doppler vibrometry (LDV).

Methods: We examined three fresh-frozen temporal bones (TB), two donated by white males and one by a Black female, using dynamic synchrotron-based X-ray microtomography for 256 and 512 Hz, stimulated at 110 dB and 120 dB sound pressure level (SPL).

High-resolution national radon maps based on massive indoor measurements in the United States.

Radon, a common radioactive indoor air pollutant, is the second leading cause of lung cancer in the United States. Knowledge about its distribution is essential for risk assessment and designing efficient protective regulations. However, the three current radon maps for the United States are unable to provide the up-to-date, high-resolution, and time-varying radon concentrations.

Comparing prediction accuracy for 30-day readmission following primary total knee arthroplasty: the ACS-NSQIP risk calculator versus a novel artificial neural network model.

Background: Unplanned readmission, a measure of surgical quality, occurs after 4.8% of primary total knee arthroplasties (TKA). Although the prediction of individualized readmission risk may inform appropriate preoperative interventions, current predictive models, such as the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) surgical risk calculator (SRC), have limited utility.

Who participates in the 'Celebrate Recovery' mutual-help organization? Results from a National US Investigation.

Introduction: Celebrate Recovery (CR) is a new, rapidly growing mutual-help organization (MHO) based on Christian principles and is the largest religious MHO in the US. However, very little is known about CR empirically.

Methods: Secondary data analysis of the National Recovery Study (NRS) (Kelly et al.

A divergent two-domain structure of the anti-Müllerian hormone prodomain.

TGFβ family ligands are synthesized as precursors consisting of an N-terminal prodomain and C-terminal growth factor (GF) signaling domain. After proteolytic processing, the prodomain typically remains noncovalently associated with the GF, sometimes forming a high-affinity latent procomplex that requires activation. For the TGFβ family ligand anti-Müllerian hormone (AMH), the prodomain maintains a high-affinity interaction with its GF that does not render it latent.

Bilingual Perspectives of Functional Dyspepsia Management in People from Underserved Areas.

Introduction: Disorders of gut-brain interaction (DGBIs), like functional dyspepsia (FD), are prevalent and challenging conditions. In other gastrointestinal (GI) disorders, individuals from underserved areas (UAs) have difficulty accessing care. Little is known about UA FD patient perspectives of their care, especially in those with limited English proficiency (LEP).

Uncertainty estimation in diagnosis generation from large language models: next-word probability is not pre-test probability.

Objective: To evaluate large language models (LLMs) for pre-test diagnostic probability estimation and compare their uncertainty estimation performance with a traditional machine learning classifier.

Materials And Methods: We assessed 2 instruction-tuned LLMs, Mistral-7B-Instruct and Llama3-70B-chat-hf, on predicting binary outcomes for Sepsis, Arrhythmia, and Congestive Heart Failure (CHF) using electronic health record (EHR) data from 660 patients. Three uncertainty estimation methods-Verbalized Confidence, Token Logits, and LLM Embedding+XGB-were compared against an eXtreme Gradient Boosting (XGB) classifier trained on raw EHR data.

Cerebrovascular reactivity: a stress test of brain vascular health in moyamoya disease.

This scientific commentary refers to 'Cerebrovascular reactivity and response times describe recent ischemic symptomatology in patients with moyamoya', by Han .  (https://doi.org/10.

Neurogenic inflammation and itch in barrier tissues.

Once regarded as distinct systems, the nervous system and the immune system are now recognized for their complex interactions within the barrier tissues. The neuroimmune circuitry comprises a dual-network system that detects external and internal disturbances, providing critical information to tailor a context-specific response to various threats to tissue integrity, such as wounding or exposure to noxious and harmful stimuli like pathogens, toxins, or allergens. Using the skin as an example of a barrier tissue with the polarized sensory neuronal responses of itch and pain, we explore the molecular pathways driving neuronal activation and the effects of this activation on the immune response.

Metabolic Adaptation and Its Determinants in Adolescents Two Years After Sleeve Gastrectomy.

Weight loss is associated with reductions in resting energy expenditure (REE), which are impacted by changes in body composition following sleeve gastrectomy (SG). Current data regarding changes in measured REE (mREE) and metabolic adaptation in adolescents after SG are limited. We evaluated changes in mREE, metabolic adaptation, and body composition in youths after SG vs.

Optimized Prime Editing of Human Induced Pluripotent Stem Cells to Efficiently Generate Isogenic Models of Mendelian Diseases.

Prime editing (PE) is a CRISPR-based tool for genome engineering that can be applied to generate human induced pluripotent stem cell (hiPSC)-based disease models. PE technology safely introduces point mutations, small insertions, and deletions (indels) into the genome. It uses a Cas9-nickase (nCas9) fused to a reverse transcriptase (RT) as an editor and a PE guide RNA (pegRNA), which introduces the desired edit with great precision without creating double-strand breaks (DSBs).

Recent developments in myeloid immune modulation in cancer therapy.

Myeloid cells play a crucial dual role in cancer progression and response to therapy, promoting tumor growth, enabling immune suppression, and contributing to metastatic spread. The ability of these cells to modulate the immune system has made them attractive targets for therapeutic strategies aimed at shifting their function from tumor promotion to fostering antitumor immunity. Therapeutic approaches targeting myeloid cells focus on modifying their numbers, genetics, metabolism, and interactions within the tumor microenvironment.