Mechanisms and rationales of SAM homeostasis.

S-Adenosylmethionine (SAM) is the primary methyl donor for numerous cellular methylation reactions. Its central role in methylation and involvement with many pathways link its availability to the regulation of cellular processes, the dysregulation of which can contribute to disease states, such as cancer or neurodegeneration. Emerging evidence indicates that intracellular SAM levels are maintained within an optimal range by a variety of homeostatic mechanisms.

The Clinical Utility of Incorporating Next-Generation Sequencing Results in the Management Algorithm of Pancreatic Cysts.

Background & Aims: Pancreatic cysts often pose challenges in predicting malignant progression. Next-generation sequencing has become an appealing ancillary diagnostic test. The diagnostic performance is well characterized, but the impact on clinical management remains unclear.

Metabolomics signatures of serotonin reuptake inhibitor (escitalopram), serotonin norepinephrine reuptake inhibitor (duloxetine) and cognitive-behavioral therapy on key neurotransmitter pathways in major depressive disorder.

Metabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this exploratory study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive-Behavioral Therapy (CBT) in 163 treatment-naïve outpatients with major depressive disorder. Serum samples from baseline and 12 weeks post-treatment were analyzed using targeted liquid chromatography-electrochemistry for metabolites related to tryptophan, tyrosine metabolism and related pathways.

Eighth Annual Society of Thoracic Surgeons Pedimacs Report.

Background: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), supported by The Society of Thoracic Surgeons, provides detailed information on pediatric patients supported with ventricular assist devices (VADs).

Methods: From September 19, 2012, to December 31, 2023, there were 1648 devices in 1349 patients (<19 years) from 39 North American Hospitals with 100 patients enrolled in 2023.

Results: Cardiomyopathy was the most common underlying etiology (59%), followed by congenital heart disease (26%) and myocarditis (8%).

Peptide nucleic acids: Recent advancements and future opportunities in biomedical applications.

Peptide nucleic acids (PNA), synthetic molecules comprising a peptide-like backbone and natural and unnatural nucleobases, have garnered significant attention for their potential applications in gene editing and other biomedical fields. The unique properties of PNA, particularly enhanced stability/specificity/affinity towards targeted DNA and RNA sequences, achieved significant attention recently for gene silencing, gene correction, antisense therapy, drug delivery, biosensing and other various diagnostic aspects. This review explores the structure, properties, and potential of PNA in transforming genetic engineering including potent biomedical challenges.

Fluoroquinolones and rifampin combination in the backdrop of heteroresistant tuberculosis.

The impact of heteroresistance on tuberculosis (TB) treatment outcomes is unclear, as is the role of different rifampin and isoniazid exposures on developing resistance mutations. Hollow fiber system model of TB (HFS-TB) units were inoculated with drug-susceptible () and treated with isoniazid and rifampin exposure identified in a clinical trial as leading to treatment failure and acquired drug resistance. Systems were sampled for drug concentration measurements, estimation of total and drug-resistant , and small molecule overlapping reads (SMOR) analysis for the detection of heteroresistance.

Nocturnal pulse oxygen saturation dynamics at simulated high altitude: Predictive value for acute mountain sickness in healthy men born pre-term.

The physiological sequelae of pre-term birth might influence the responses of this population to hypoxia. Moreover, identifying variables associated with development of acute mountain sickness (AMS) remains a key practically significant area of altitude research. We investigated the effects of pre-term birth on nocturnal oxygen saturation ( ) dynamics and assessed the predictive potential of nocturnal -related metrics for morning AMS in 12 healthy adults with gestational age < 32 weeks (pre-term) and 12 term-born control participants.

Cardiovascular Disease Risk in South Asians in the Baylor Scott and White Health DILWALE Registry.

Background: Despite implementation of preventive interventions targeting cardiovascular disease (CVD), atherosclerotic CVD (ASCVD) remains a major public health concern in the South Asian (SA) population.

Objectives: The purpose of this study was to assess the risk factor prevalence and ASCVD outcomes in SA population in the United States.

Methods: The DIL Wellness and Arterial health Longitudinal Evaluation registry collected data retrospectively on SA adult patients receiving care in the Baylor Scott & White Healthcare system.

Temporomandibular disorders: A new list of key points to summarize the standard of care.

This letter is being sent to editors of major dental journals around the world. Attached to it is an Announcement that summarizes a recently published position paper which deals with the topic of standards of care for Temporomandibular Disorders (TMDs). That paper, entitled "Temporomandibular disorders: INfORM/IADR key points for good clinical practice based on standard of care", was developed by a group of expert researchers and clinicians over a one-year period.

Cancer-targeted pro-theranostic bi-metallic organo-coordination nanoparticles.

Cancer remains a leading cause of mortality, with aggressive, treatment-resistant tumors posing significant challenges. Current combination therapies and imaging approaches often fail due to disparate pharmacokinetics and difficulties correlating drug delivery with therapeutic response. In this study, we developed radionuclide-activatable theranostic nanoparticles (NPs) comprising folate receptor-targeted bimetallic organo-nanoparticles (Gd-Ti-FA-TA NPs).

Pulmonary artery choriocarcinoma mimicking pulmonary thromboembolism: a case report.

Background: Primary choriocarcinoma of the pulmonary artery is an exceedingly rare malignant neoplasm, which is often misdiagnosed due to its nonspecific clinical presentation. While this condition is characterized by the presence of trophoblastic cells, typically associated with gestational trophoblastic diseases, we encountered a case occurring in an extragenital location. The rarity of such tumors makes it challenging for clinicians to consider them in differential diagnosis, especially when the initial symptoms mimic more common conditions such as pulmonary thromboembolism (PTE).

Inflammatory pseudotumor-like extranodal classic Hodgkin lymphoma manifesting as bowel perforation in acquired immunodeficiency syndrome patient with disseminated leishmaniasis: a case report and approach to differential diagnosis.

Background: Classic Hodgkin lymphoma (CHL) is an extremely common non-acquired immunodeficiency syndrome (AIDS) defining malignancy and its incidence is rising. CHL is usually present in the lymph node and extranodal involvement is rare. Primary CHL of the gastrointestinal (GI) tract is exceedingly rare.

Global Review of Tools Evaluating Quality of Life in Cervical Cancer Survivors Treated With Chemoradiation Therapy.

Purpose: This systematic review aimed to identify and compare tools used to evaluate quality of life (QoL) after pelvic radiation for cervical cancer and to describe variations in results within commonly used instruments. This review hypothesized regional preferences in the selection of these tools and an absence of uniformity in their application globally.

Methods And Materials: A comprehensive search of 6 databases was conducted between the inception of each included database and June 14, 2023, focusing on studies evaluating the QoL of patients with cervical cancer during and after radiation.

Non-language neuropsychological measures increase sensitivity of identifying language reorganization in patients with epilepsy: a pilot study.

Objective: To examine neuropsychological characteristic differences between typical and atypical language dominance in adult persons with epilepsy (PWE) and mesial temporal sclerosis (MTS), including exploring the impact of selected clinical variables on detection of atypical language and neuropsychological performance.

Methods: Adults with intractable epilepsy and MTS ( = 39) underwent comprehensive, pre-surgical evaluation including fMRI and neuropsychological assessment. Participants with concordant lateralization of MTS and seizure onset were included.

Cholangioblastic Cholangiocarcinoma (NIPBL::NACC1 cholangiocarcinoma): Expanded Morphologic Spectrum and Further Genetic Characterization.

The cholangioblastic variant of intrahepatic cholangiocarcinoma is a distinctive neoplasm that typically affects young women without underlying liver disease. Morphologically, it demonstrates solid, trabecular, and tubulocystic architecture, biphasic small cell-large cell cytology, and immunoreactivity for inhibin, neuroendocrine markers, and biliary but not hepatocellular markers. In 2021, our group identified a characteristic NIPBL::NACC1 gene fusion in cholangioblastic cholangiocarcinoma, and since then ~20 genetically confirmed cases have been reported in the literature.

Evaluation of synaptotagmin-1 action models by all-atom molecular dynamics simulations.

Neurotransmitter release is triggered in microseconds by the two C domains of the Ca sensor synaptotagmin-1 and by SNARE complexes, which form four-helix bundles that bridge the vesicle and plasma membranes. The synaptotagmin-1 CB domain binds to the SNARE complex via a 'primary interface', but the mechanism that couples Ca-sensing to membrane fusion is unknown. Widespread models postulate that the synaptotagmin-1 Ca-binding loops accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers or helping bridge the membranes, but these models do not seem compatible with SNARE binding through the primary interface, which orients the Ca-binding loops away from the fusion site.

Bullying in adolescents across three years in the context of the COVID-19 pandemic: a repeated cross-sectional and prospective analysis.

Background: Bullying has been identified as a risk factor for many issues among adolescents. Although it was already considered a public health issue in Brazil before the COVID-19 pandemic, little is known about how the pandemic and associated public health measures have affected bullying behavior.

Objective: To explore changes in bullying victimization and perpetration among Brazilian high school students from 2019 to 2022.

The microcephaly-associated transcriptional regulator AUTS2 cooperates with Polycomb complex PRC2 to produce upper-layer neurons in mice.

AUTS2 syndrome is characterized by intellectual disability and microcephaly, and is often associated with autism spectrum disorder, but the underlying mechanisms, particularly concerning microcephaly, remain incompletely understood. Here, we analyze mice mutated for the transcriptional regulator AUTS2, which recapitulate microcephaly. Their brains exhibit reduced division of intermediate progenitor cells (IPCs), leading to fewer neurons and decreased thickness in the upper-layer cortex.

Orthogonalized human protease control of secreted signals.

Synthetic circuits that regulate protein secretion in human cells could support cell-based therapies by enabling control over local environments. Although protein-level circuits enable such potential clinical applications, featuring orthogonality and compactness, their non-human origin poses a potential immunogenic risk. In this study, we developed Humanized Drug Induced Regulation of Engineered CyTokines (hDIRECT) as a platform to control cytokine activity exclusively using human-derived proteins.

Did Finerenone Improve Health Status in the FINEARTS Trial?: A Critical Reevaluation of the Analysis of Patient-Reported Outcomes in Heart Failure.

Patient-reported health status is an important assessment of patients with heart failure, but current approaches have substantial methodological and analytical limitations. Changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) are commonly presented as a measure of the effect of drugs and devices, most often as the between-group difference in population means or as the odds of showing threshold changes of 5, 10, 15, and 20 points. However, the presentation of mean differences is based on statistical assumptions that are routinely violated in most trials.

Association between abatacept exposure levels and infection occurrence in patients with rheumatoid arthritis: post hoc analysis of the AVERT-2 study.

Objective: To determine if higher serum exposure during subcutaneous (SC) abatacept treatment was associated with an increased infection risk in adult patients with early rheumatoid arthritis (RA).

Methods: Data from AVERT-2 (Assessing Very Early Rheumatoid arthritis Treatment-2, NCT02504268), a randomized, placebo-controlled study in anticitrullinated protein antibody- positive patients with early RA, were analyzed. A post hoc population pharmacokinetic (PPK) analysis was performed.

Approach to the Patient with Achondroplasia - New Considerations for Diagnosis, Management and Treatment.

Achondroplasia is the most common disproportionate short-stature skeletal dysplasia. Features associated with achondroplasia are rhizomelia, macrocephaly, midface hypoplasia, and typical cognition. Potential medical complications include foramen magnum stenosis, hydrocephalus, middle ear dysfunction, obstructive and central sleep apnea, spinal stenosis and genu varum.