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SIR2-mediated filament assembly activates the NLR-like protein Avs5 for bacterial antiviral defense
Like mammalian nucleotide-binding and oligomerization domain receptors (NLRs), bacterial NLR-like proteins mediate antiviral defense. Avs5, a representative of a large family of short bacterial NLR-like proteins, contains an N-terminal SIR2 effector, a central nucleotide-binding domain (NBD), and a C-terminal sensor domain. Whereas canonical inflammasome NLRs use NBD oligomerization to nucleate ef...
The lncRNA Statera regulates synaptogenesis by repressing the retrotransposon copia in Drosophila
Retrotransposons are mobile genetic elements that can impair genome integrity, and their insertions and dysregulation have been implicated in various diseases. However, growing evidence suggests that retrotransposons may play important physiological roles. At the Drosophila larval neuromuscular junction (NMJ), the ViSyToR (Viral Synaptic Transfer of RNA) pathway requires the active retrotransposon...
Weight Gain During Successful Tuberculosis Treatment Increases the Risk of Post-tuberculosis Metabolic Syndrome
CONCLUSIONS: Among individuals who were successfully treated, individuals who had a ≥5% increase in BMI during TB treatment had a significantly increased risk of metabolic syndrome and higher HbA1c levels up to 12 months after TB treatment.
Jail-based opioid treatment implementation, outcomes, and costs: lessons learned from the Massachusetts Justice Community Opioid Innovation Network (MassJCOIN)
Limited access to medications for opioid use disorder (MOUD) is a major driver of the opioid overdose crisis. Jails have been slow to implement MOUD treatment, especially agonist medications (methadone, buprenorphine). Massachusetts mandated certain county jails pilot-test delivery of all FDA-approved MOUD treatments, stipulating jails continue MOUD, or initiate it prior to release, and facilitate...
TAICHIKNEE trial: protocol for an embedded pragmatic, individually randomised group-treatment trial of remotely delivered Tai Chi for knee osteoarthritis across US healthcare systems
No abstract
Factors Associated With Clinical Trial Participation in Adult Hematopoietic Stem Cell Transplantation Recipients: A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis
CONCLUSIONS: Clinical trial participation remains low, particularly among autologous HSCT recipients, younger adults, and patients with specific diagnoses. Findings highlight the need to broaden trial eligibility, enhance outreach, and ensure equity in trial access to promote generalizable, patient-centered evidence in HSCT.
Structural basis for start codon selection by eIF5-mimic proteins
Start codon selection extensively regulates the cellular proteome and is implicated in cancer and other diseases. The eIF5-mimic proteins (5MPs: 5MP1/BZW2 and 5MP2/BZW2) restrict non-AUG start codon usage and thereby reprogram proteoform expression from mRNAs with alternative start sites, such as the oncogenic c-Myc. Here, using in extracto cryo-electron microscopy (cryo-EM) and biochemical assays...
Whipple Disease: A Two-Decade Multisystem Masquerade Preceding Gastrointestinal Presentation
Whipple disease is a rare multisystem infection caused by Tropheryma whipplei that can present with extraintestinal manifestations preceding gastrointestinal symptoms by years. We report an unusually prolonged course in a patient with nearly 2 decades of treatment-refractory seronegative inflammatory polyarthritis who later developed gastrointestinal symptoms. Although initial upper endoscopy with...
MRI Interpretation of Suspected Pediatric Acute Appendicitis: The Role of Pediatric Subspecialty Training
CONCLUSION: Fellowship-trained pediatric radiologists had higher specificity, positive predictive value, and accuracy than non-pediatric emergency radiologists for MRI diagnosis of suspected pediatric AA, with a small difference in interpretation time (median, 24 seconds). These findings, based on a limited number of readers, suggest differences in subspecialty expertise and aims and support furth...
Whole person health in epilepsy: prioritizing care-partner wellbeing
The experiences of care-partners of people with epilepsy are complex and dynamic throughout the lifespan, yet their wellbeing remains insufficiently recognized within care systems. There is a public health need to examine and address the wellbeing of epilepsy care-partners. Utilizing the National Institute of Health (NIH) Whole Person Health framework, we present a narrative synthesis of often-ove...
Gene conversion is a key driver of diversity hotspots in Mycobacterium tuberculosis antigens and virulence-associated loci
Despite the long-held view of Mycobacterium tuberculosis (Mtb) as a genetically conserved pathogen, many genomic regions remain poorly resolved due to high sequence homology and repetitive content. Using complete genome assemblies generated from long-read sequencing of 151 globally representative clinical isolates, we comprehensively analyzed genome-wide patterns of genetic diversity and evolution...
A cog in the Weil: A case report of severe leptospirosis
The nonspecific presentation of leptospirosis and delays in serologic confirmation often make its diagnosis challenging. The presence of comorbidities or potential drug toxicities, which can mimic or obscure clinical findings, further adds to this diagnostic difficulty. Here, we present the case of a 46-year-old male with well-controlled HIV infection on antiretroviral therapy, who presented with ...
ASFNR Clinical State of Practice Statement on Imaging of Chronic Subdural Hematoma
BACKGROUND: The efficacy of middle meningeal artery embolization (MMAE) for chronic subdural hematoma (cSDH) has heightened interest in imaging biomarkers that may reflect neomembrane activity, predict recurrence, and identify patients most likely to benefit from treatment. Characterization of hematoma internal architecture, referred to as the imaging phenotype, may provide indirect information re...
Preventing perinatal depression relapse
No abstract
Spontaneous pneumorrhachis in adolescents: illustrative case
BACKGROUND: Spontaneous pneumorrhachis, defined as the presence of air in the spinal canal without trauma or iatrogenic intervention, is rare in adolescents. The clinical course remains anecdotal, and no standardized management guidelines exist. The authors performed the first systematic review focused on adolescent spontaneous pneumorrhachis and describe an illustrative case.
Programmable gold nanoparticle conjugates enable precise AMPA receptor localization at brain synapses by cryo-ET
Cryo-electron tomography (cryo-ET) is a powerful approach to image cells, organelles, viruses and molecular assemblies. However, resolving smaller complexes and molecules is challenging and presents a roadblock to the broad application of cryo-ET. Gold nanoparticles (AuNPs) have been used to localize otherwise unidentifiable molecules and complexes in tomograms but are typically tethered to the ta...
Massive Upper Gastrointestinal Bleeding in an Adolescent Patient: A Case Report
BACKGROUND: Gastrointestinal (GI) bleeding in pediatric patients arises from diverse etiologies that vary across age groups. Although it is an uncommon cause of life-threatening hemorrhagic shock, prompt recognition and management are essential. Owing to the infrequency of hemorrhagic shock from GI bleeding in pediatrics, emergency physicians may lack familiarity with its diagnosis and management....
The cochlear macrophage in presbycusis: inflammaging, neuroinflammation, and targets for therapeutic modulation
Age-related neurodegenerative diseases and age-related hearing loss are increasing in prevalence globally. Immune cells are novel mediators linking these diseases through shared mechanisms of chronic inflammation and maladaptive repair. In the cochlea, resident macrophages and infiltrating immune cells respond to injury, noise exposure, and aging by adopting activated phenotypes that disrupt synap...
Modeling Moyamoya disease using patient-derived induced pluripotent stem cells and organoids
The underlying mechanisms of Moyamoya disease (MMD), a rare, progressive cerebrovascular disorder marked by distal internal carotid artery stenosis or occlusion and the formation of fragile collaterals, remain poorly understood, in part because conventional models fail to capture the genetic, vascular, and neurovascular complexity of human MMD. Driven by recent advances in disease modeling, MMD re...
Contemporary Clinical Outcomes and Healthcare Utilization in Older Adults with Acute Myeloid Leukemia: Insights from a Single-Center Retrospective Cohort
CONCLUSIONS: Our findings highlight real-world challenges for older adults with AML, including the need for more effective treatments for patients with TP53-mutated AML. AML-directed treatment was associated with longer survival without a decrease in the time spent in hospice care, and the risk of in-hospital mortality remains elevated for this population.
Minimally Invasive Surgical Approaches to Colorectal Cancer: Learning Curve and Cost Considerations
Minimally invasive surgical (MIS) techniques have fundamentally transformed the management of colorectal cancer. Since the early 1990s, the field has rapidly evolved, shifting from initial concerns about oncologic safety to the widespread adoption of both laparoscopic and robotic surgeries. Specifically, laparoscopic approaches to colorectal cancer resection are now widely adopted and supported by...
Lymphedema Management in May-Thurner Syndrome: A Case Series of 26 Patients
Background: May-Thurner syndrome (MTS) is an uncommon cause of deep vein thrombosis and unilateral lower extremity lymphedema. We present the largest case series to date of 26 MTS patients with lymphedema. We aim to report the pathophysiology of lymphedema in relation to venous dysfunction onset in MTS patients and evaluate the effectiveness of surgical lymphedema treatment. Methods: Retrospective...
Social Risk Screening and Referrals in the Pediatric Inpatient Setting
CONCLUSIONS: Social risk screening and referral practices vary widely among hospitals caring for children. Standardized policies and support mechanisms may reduce variability and promote equitable social care practices across hospitals.
Close Call: Fever, Rash, and Neck Swelling in a Female Sex Worker
No abstract
Understanding the Influence of Substance Use, Mental Health, and Stigma on Smoking Behavior Among People Living With HIV: Rapid Qualitative Analysis
CONCLUSIONS: Smoking behaviors among people living with HIV are shaped by overlapping influences, including societal norms, mental health, HIV-related stigma, and other structural stressors. An understanding of these overlapping factors can inform the development of text-based interventions that offer effective cessation support tailored to this population.
Oral azacitidine as time-limited, PCR-dependent maintenance in acute myeloid leukemia with inv(16): two case reports
Core-binding factor acute myeloid leukemia (CBF-AML) in fit patients is treated with curative-intent induction chemotherapy followed by 3-4 cycles of high-dose cytarabine (HiDAC) consolidation. No standard therapy exists for patients with contraindications to HiDAC consolidation. Oral azacitidine is approved as indefinite maintenance therapy for intermediate/high risk AML but has not been studied ...
EACTS/STS/AATS Guidelines on Temporary Mechanical Circulatory Support in Adult Cardiac Surgery: An Expert Analysis for Cardiothoracic Anesthesia and Critical Care
No abstract
Mitochondrial stress induces transcription of cytosolic and mitochondrial protein synthesis components via NHR-180
The mitochondrial unfolded protein response (UPR^(mt)), which promotes mitochondrial biogenesis and proteostasis, is regulated by the transcription factor ATFS-1. In C. elegans, impaired atfs-1 expression perturbs mitochondrial function and slows development. Here, using an RNAi suppressor screen, we find that inhibition of the nuclear hormone receptor NHR-180 increases mitochondrial function and ...
Protocol and rationale for a randomised, double-blind, placebo-controlled phase 3 trial of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with idiopathic pulmonary fibrosis: ALOFT-IPF
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is associated with progressive loss of lung function and poor prognosis. There remains a need for novel therapies for patients with IPF. Admilparant, an oral lysophosphatidic acid receptor 1 antagonist, slowed lung function decline and was well tolerated in a phase 2 trial when administered 60 mg two times per day in patients with IPF over 26 weeks...
Fragment OptimizationSimple SMILES String Manipulation Strategies to Optimize a Hit or Fragment
AI/ML-based tools for generative and predictive modeling have become important contributors to small molecule drug discovery, enabling virtual compound design and ADME profiling prior to synthesis. Alongside these methods, simpler nonlearned strategies based on direct SMILES manipulation remain useful, particularly for low data targets. Herein is described a method for fragment optimization in whi...
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