Age-associated differences in FIRES: Characterizing prodromal presentation and long-term outcomes via the web-based NORSE/FIRES Family Registry.

Febrile infection-related epilepsy syndrome (FIRES) is a rare clinical presentation of refractory status epilepticus following a febrile infection. This study analyzes data from the NORSE/FIRES Family Registry, an international web-based registry available in six languages with data entered by patients, families, and clinicians to explore clinical presentations, survivorship, and long-term outcomes in adult and pediatric FIRES patients. We characterize and examine differences in demographics, prodromal symptoms, seizure frequency, anti-seizure medications (ASMs), quality of life, cognition, mood, and anxiety in adults vs pediatric populations with FIRES.

Protein tyrosine phosphatase PTPH1 potentiates receptor tyrosine kinase HER2 oncogenesis via a PDZ-coupled and phosphorylation-driven scaffold.

Cancer cell overexpresses numerus proteins, however, how these up-regulated proteins, especially those enzymatically opposite kinases and phosphatases, act together to promote oncogenesis is unknown. Here, we reported that protein tyrosine phosphatase H1 (PTPH1) is a scaffold protein for receptor tyrosine kinase (HER2) to potentiate breast tumorigenesis. PTPH1 utilizes its PDZ domain to bind HER2, p38γ, PBK, and YAP1 and to increase HER2 nuclear translocation, stemness, and oncogenesis.

2024 HRS perspective on advancing workflows for CIED remote monitoring.

Cardiac implantable electronic devices (CIEDs) generate substantial data, often stored in image or PDF formats. Remote monitoring, now an integral component of patient care, places considerable administrative burdens on clinicians and staff, in large part due to the challenge of integrating these data seamlessly into electronic health records. Since 2006, the Heart Rhythm Society, in collaboration with the CIED industry, has led an initiative to establish a unified standard nomenclature.

Recessive but damaging alleles of muscle-specific ribosomal protein gene drive neonatal dilated cardiomyopathy.

The heart employs a specialized ribosome in its muscle cells to translate genetic information into proteins, a fundamental adaptation with an elusive physiological role. Its significance is underscored by the discovery of neonatal patients suffering from often fatal heart failure caused by rare compound heterozygous variants in RPL3L, a muscle-specific ribosomal protein that replaces the ubiquitous RPL3 in cardiac ribosomes. -linked heart failure represents the only known human disease arising from mutations in tissue-specific ribosomes, yet the underlying pathogenetic mechanisms remain poorly understood despite an increasing number of reported cases.

Association between peripartum cardiomyopathy and mood disorders in a large, national U.S. cohort.

Objective: To examine the association between mood disorders in pregnancy and postpartum and peripartum cardiomyopathy (PPCM).

Methods: Retrospective cohort study utilizing the National Inpatient Sample from the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality of pregnant and postpartum patients from 2017-2019. Patients were separated into two groups based on ICD-10 coding for presence or absence of mood disorder (depression, bipolar depression, anxiety, or other mood diagnosis).

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.

Effectiveness and safety of oral vancomycin for the treatment of inflammatory bowel disease associated with primary sclerosing cholangitis: a systematic review and pooled analysis.

Background: Inflammatory bowel disease (IBD) occurs in up to 70%-80% of patients with primary sclerosing cholangitis (PSC). Oral vancomycin therapy (OVT) has been reported to be effective in the treatment of IBD associated with PSC (IBD-PSC).

Objectives: To examine the effectiveness and safety of OVT in the treatment of IBD-PSC by performing a systematic review and pooled analysis of the literature.

Abnormal redox balance at membrane contact sites causes axonopathy in -related Charcot-Marie-Tooth disease.

Pathogenic variants of cause Charcot-Marie-Tooth disease (CMT), an inherited neuropathy characterized by axonal degeneration. GDAP1, an atypical glutathione S-transferase, localizes to the outer mitochondrial membrane (OMM), regulating this organelle's dynamics, transport, and membrane contact sites (MCSs). It has been proposed that GDAP1 functions as a cellular redox sensor.

Delayed primacy recall in AVLT is associated with medial temporal tau PET burden in cognitively unimpaired adults.

Background: Alzheimer's disease (AD) can be diagnosed by in vivo abnormalities of amyloid-β plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions.

A Lu-nucleotide coordination polymer-incorporated thermosensitive hydrogel with anti-inflammatory and chondroprotective capabilities for osteoarthritis treatment.

Osteoarthritis (OA) is a prevalent and debilitating condition characterized by cartilage destruction and inflammation. Traditional pharmacotherapies for OA are limited by their short-term efficacy and systemic side effects. Radiosynoviorthesis (RSO), involving intra-articular injection of radiopharmaceuticals, has shown promise for OA treatment but is hindered by the toxicity and rapid clearance of radioisotopes.

Safety of accessing brachial veins for large-bore upper extremity venous thrombectomy using ClotTriever Thrombectomy System.

Purpose: To evaluate access site adverse events following ClotTriever-mediated large-bore mechanical thrombectomy via small upper extremity deep veins (< 6-mm).

Materials And Methods: Twenty patients, including 24 upper extremity venous access sites, underwent ClotTriever-mediated large-bore thrombectomy of the upper extremity and thoracic central veins for symptomatic deep vein obstruction unresponsive to anticoagulation. Patients without follow-up venous duplex examinations (n = 3) were excluded.

Rural nonprofit hospital community benefit and financial assistance spending: A call for greater reporting transparency.

Purpose: US nonprofit hospitals must provide community benefits including financial assistance to be tax-exempt. Rural residents particularly benefit from financial assistance because they have higher medical debt on average. The Internal Revenue Service allows nonprofit hospitals that are members of health systems to report expenditures for their entire system (group returns) rather than for individual hospitals.

Dereplication of Natural Product Antifungals via Liquid Chromatography-Tandem Mass Spectrometry and Chemical Genomics.

Recently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we have integrated Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for structural dereplication and Yeast Chemical Genomics for bioprocess evaluation into a screening platform to identify such compounds early in the screening process. We identified 450 fractions inhibiting and the resistant strains of and among more than 40,000 natural product fractions.

Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis.

Gut bacterial metabolism of dietary flavonoids results in the production of a variety of phenolic acids, whose contributions to health remain poorly understood. Here, we show that supplementation with the commonly consumed flavonoid quercetin impacted gut microbiome composition and resulted in a significant reduction in atherosclerosis burden in conventionally raised (ConvR) Apolipoprotein E (ApoE) knockout (KO) mice but not in germ-free (GF) ApoE KO mice. Metabolomic analysis revealed that consumption of quercetin significantly increased plasma levels of benzoylglutamic acid, 3,4 dihydroxybenzoic acid (3,4-DHBA) and its sulfate-conjugated form in ConvR mice, but not in GF mice supplemented with the flavonoid.

Lentivirus-mediated gene therapy for Fabry disease: 5-year End-of-Study results from the Canadian FACTs trial.

Background: Fabry disease is an X-linked lysosomal storage disorder due to a deficiency of α-galactosidase A (α-gal A) activity. Our goal was to correct the enzyme deficiency in Fabry patients by transferring the cDNA for α-gal A into their CD34+ hematopoietic stem/progenitor cells (HSPCs). Overexpression of α-gal A leads to secretion of the hydrolase; which can be taken up and used by uncorrected bystander cells.

The International System for Serous Fluid Cytopathology (TIS) survey in preparation for TIS 2.0.

Introduction: The International System for Serous Fluid Cytopathology (TIS) has gained acceptance and has led to literature validating original concepts and suggesting refinements. In preparation for the second edition of TIS, editors generated a survey to solicit experience with and opinions about TIS.

Materials And Methods: An online survey available from March 8 to June 15, 2024, included 56 questions, offered in 7 languages, related to the practice of serous fluid cytopathology.

Results of a Global Survey on the State of Interventional Radiology 2024.

Purpose: To understand the state of IR practice and education worldwide and identify factors impacting access to IR services.

Methods And Materials: A Society of Interventional Radiology (SIR) approved anonymous survey was created to gather demographics, regional IR practice and education characteristics, and challenges impacting local IR development. The survey was distributed to members of global IR societies and shared on social media from 6/2022 to 9/2023.

Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.

Voices of Nanomedicine: Blueprint Guidelines for Collaboration in Addressing Global Unmet Medical Needs.

The "" under this Perspective underline the importance of interdisciplinary collaboration and partnerships across several disciplines, such as medical science and technology, medicine, bioengineering, and computational approaches, in bridging the gap between research, manufacturing, and clinical applications. Effective communication is key to bridging team gaps, enhancing trust, and resolving conflicts, thereby fostering teamwork and individual growth toward shared goals. Drawing from the success of the COVID-19 vaccine development, we advocate the application of similar collaborative models in other complex health areas such as nanomedicine and biomedical engineering.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Assessment of the European Hernia Society Classification of Ventral Hernias and Clinical Outcomes.

Background: Ventral hernias are a common but heterogeneous disease. Communication among key stakeholders (eg, patients, clinicians, administrators, payers, and researchers) can be augmented by a widely utilized classification system. The European Hernia Society (EHS) developed an expert-opinion-based hernia classification system organized by hernia type (primary versus incisional) and size.

UW supplementation with AP39 improves liver viability following static cold storage.

Static cold storage of donor livers at 4 °C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (HS) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. HS is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations.

Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial.

Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC.

Dysregulation of Airway and Systemic Interferon Responses Promote Asthma Exacerbations in Urban Children.

Background: Determining why some upper respiratory illnesses provoke asthma exacerbations remains an unmet need.

Objective: To identify transcriptome-wide gene expression changes associated with colds that progress to exacerbation.

Methods: 208 urban children (6-17 years) with exacerbation-prone asthma were prospectively monitored for up to two cold illnesses.