Digital Commons Network^™

The Gut Microbiota Shapes The Human And Murine Breath Volatilome, Ariel J Hernandez-Leyva, Amalia Z Berna, Maggie H Bui, Yang Liu, Anne L Rosen, Michael A Lint, Samantha A Whiteside, Natalia Jaeger, Ryan T Mcdonough, Nikhilesh Joardar, Jesús Santiago-Borges, Christopher P Tomera, Wentai Luo, Audrey R Odom John, Andrew L Kau

2020-Current year OA Pubs

The gut microbiota is crucial to health, yet implementation of microbiota-based therapeutics is limited by the lack of rapid diagnostics. We hypothesize that breath contains gut microbe-derived volatile organic compounds (VOCs) reflecting microbiota composition and metabolism. In healthy children, we found that breath VOC composition (or volatilome), assessed by gas chromatography-mass spectrometry, correlates with gut microbiome composition and function. By capturing exhaled breath from human-stool-colonized and monocolonized gnotobiotic mice, we profiled breath VOCs and discovered that murine breath is also significantly influenced by the gut microbiome. VOCs from cultured gut microbes were identified in vivo in monocolonized gnotobiotic colonized mice. …

Reference Proteins To Improve Core 1 And Core 2 Alzheimer's Disease Csf And Plasma Biomarkers, Linda Karlsson, Nicolas R Barthélemy, Kanta Horie, Suzanne E Schindler, Brian A Gordon, Cyrus A Raji, Tammie L S Benzinger, John C Morris, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Concentration-based fluid biomarkers represent an informative and cost-effective way to detect and monitor Alzheimer's disease (AD) pathology. However, non-AD-related interindividual variation in biofluids can also affect biomarker concentrations. Here, we investigated whether normalization of CSF and plasma biomarkers to reference proteins, such as amyloid-β40 (Aβ40) and non-phosphorylated mid-region tau (np-tau), improves their robustness and reliability of representing AD pathology load. Using the Swedish BioFINDER-2 cohort [n = 1702, 50.7% male, mean (standard deviation) age 68.4 (12.2) years], we compared the associations between tau/Aβ-PET load and fluid biomarkers alone versus biomarkers in a ratio with a reference protein (Aβ40 or np-tau) …

Ex Vivo Effect Of Apixaban On Hemostatic Biomarkers In Children With Heart Disease: A Saxophone Trial Substudy, Ghada A Aborkhees, Amy J Barr, Kevin Dietrich, Christoph Male, Zhaoqing Wang, Chen Yao, R Mark Payne, Andrew C Glatz, Paul Monagle, Kristin M Burns, Alison M Reedy, Joshua L Dyme, Peter H Schafer, Antoinette Ajavon-Hartmann, Lesley G Mitchell

2020-Current year OA Pubs

BACKGROUND: The SAXOPHONE (Safety of Apixaban on Pediatric Heart Disease on the Prevention of Embolism) trial demonstrated the safety of apixaban for thromboprophylaxis in children with heart disease. Included a priori in the trial design was an exploratory biomarker substudy to evaluate the effects of apixaban on surrogate biomarkers of efficacy, thrombin generation capacity, and hemostatic proteins. The study assessed changes in d-dimer, thrombin generation assay parameters, factor VIII, fibrinogen, protein C, and protein S in children receiving apixaban compared with standard-of-care vitamin K antagonists (VKAs) or low-molecular-weight heparin.

METHODS: SAXOPHONE participants aged >1 year (n=182) had blood samples for …

Validate-Perianal: An International Real-World Multi-Centre Exploratory Validation Of The Topclass Definition Of A Radiologically Healed Fistula In Perianal Fistulising Crohn's Disease, Easan Anand, Thirza J Van Croonenburg, Sami Samaan, Phil Tozer, Ailsa Hart, Parakkal Deepak, David H Ballard, Jaap Stoker, Phillip Lung

2020-Current year OA Pubs

OBJECTIVES: Radiological healing on MRI is the ultimate therapeutic goal in Class 2a perianal fistulising Crohn's disease (pfCD). The TOpClass consortium recently defined radiological healing (TOpClass-RH) by the absence of T2 hyperintensity, a completely fibrotic fistula tract, and the absence of contrast enhancement when used. This study aimed to validate TOpClass-RH in real-world clinical practice.

MATERIALS AND METHODS: VALIDATE-PERIANAL was a retrospective, multi-centre international study. Patients with pfCD with a baseline MRI scan showing active disease and follow-up MRI evidence of radiological fistula healing between 2021 and 2023 were identified. Paired scans were independently reviewed by three gastrointestinal radiologists using …

Mitochondrial Presequences Harbor Variable Strengths To Maintain Organellar Function, Youmian Yan, Baigalmaa Erdenepurev, Thiago N Menezes, Ian Collinson, Natalie M Niemi

2020-Current year OA Pubs

Hundreds of mitochondrial proteins rely on N-terminal presequences for organellar targeting and import. While generally described as positively charged amphiphilic helices, presequences lack a consensus motif and thus likely promote protein import into mitochondria with variable efficiencies. Indeed, the concept of presequence strength underlies biological models such as stress sensing, yet a quantitative analysis of what dictates strong versus weak presequences is lacking. Furthermore, the extent to which presequence strength affects mitochondrial function and cellular fitness remains unclear. Here, we capitalize on the MitoLuc protein import assay to define multiple aspects of presequence strength. We find that select presequences, including …

Medicare Part D Formulary Coverage Of Disease-Modifying Therapies For Multiple Sclerosis, Pengxiang Li, Matthew J Klebanoff, John K Lin, Keya D Doshi, Salim Chahin, Jalpa A Doshi

2020-Current year OA Pubs

No abstract provided.

Eeg In Patients With Altered Mental Status In The Emergency Department, Mariama Runcie, Neal Nolan, Olivia Yoo, Robert Silbergleit, Fábio A Nascimento, Maura Kennedy, M Brandon Westover, Joshua N Goldstein

2020-Current year OA Pubs

BACKGROUND: Altered mental status is a common chief complaint in the emergency setting, and the initial evaluation often fails to find an etiology. Subclinical (electrographic) seizures and nonconvulsive status epilepticus (NCSE) are potential causes of delirium and altered mental status, but require electroencephalogram (EEG) for diagnosis. It is not clear how often subclinical seizure or NCSE is present in those with undifferentiated altered mental status, nor which patients are most likely to benefit from emergent EEG. METHODS: We performed a retrospective review of patients presenting to a single academic medical center emergency department (ED) over a one-year period with the …

Depolymerizing F-Actin Accelerates The Exit From Pluripotency To Enhance Stem Cell-Derived Islet Differentiation, Nathaniel J Hogrebe, Mason D Schmidt, Punn Augsornworawat, Sarah E Gale, Mira Shunkarova, Jeffrey R Millman

2020-Current year OA Pubs

In this study, we demonstrate that cytoskeletal state at the onset of directed differentiation impacts the exit of human pluripotent stem cells (hPSCs) from pluripotency and downstream lineage specification. In particular, depolymerizing F-actin with latrunculin A (latA) during the first 24 h of definitive endoderm formation facilitates efficient loss of pluripotency and alters Activin/Nodal, BMP, c-Jun, and WNT signaling dynamics. These signaling changes influence downstream patterning of the gut tube, leading to improved pancreatic progenitor identity and decreased expression of markers associated with other endodermal lineages. Continued differentiation generates islets containing a higher percentage of β cells that exhibit improved …

Sialidosis Type I: How To Alleviate Disabling Myoclonic Seizures? - A Multicenter Analysis Of Eight Cases And Review Of The Literature, Janina Gburek-Augustat, Shao Ching Tu, Marwan Shinawi, Isabel Alfradique-Dunham, Manouela Valtcheva, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Sialidosis type I (ST-1) is an autosomal-recessive, very rare, progressive lysosomal storage disorder caused by pathogenic variants in NEU1. It is clinically characterized by progressive ataxia, myoclonic seizures (MS), bilateral tonic-clonic seizures (BTCS), and distinctive ophthalmological findings. Given the lack of curative options, in this study, we investigated symptomatic treatment strategies, with a particular focus on the efficacy of antiseizure medications (ASMs).

METHODS: We describe the clinical course of a patient followed from diagnosis to 18 years of age, and review seven additional cases from our cohort. In parallel, we conducted a narrative review of the literature (PubMed, January …

Differential Regulation Of Cyclic Adenosine Monophosphate By Phosphodiesterase 3a Discriminates Thrombin-Induced Protease Activated Receptor 1- And 4-Dependent Platelet Activation, Izabella Andrianova, Abigail Ajanel, Jesse W Rowley, Darian C Murray, Yasuhiro Kosaka, Frederik Denorme, Paul F Bray, Robert A Campbell

2020-Current year OA Pubs

BACKGROUND: Human platelets express 2 thrombin-activated G protein-coupled receptors (GPCRs), protease activated receptor (PAR)1 and PAR4. Previous studies have demonstrated PAR1 activation to be fast on-fast off while PAR4 activation was slower but more sustained. However, how PARs regulate second messengers such as cyclic adenosine monophosphate (cAMP), a negative regulator of platelet activation, remain unknown.

OBJECTIVES: This study investigated how PAR1 and PAR4 activation by thrombin regulates cAMP levels and platelet activation.

METHODS: PAR1 and PAR4 on washed human platelets were inhibited with vorapaxar or BMS-986120, respectively, in the presence or absence of prostaglandin (PG)I

RESULTS: In the presence of …

Lyplal1 Rare Loss-Of-Function Variants In Humans And Deletion In Human Hepatoma Cells Protect Against Masld, Rawdat Hussain, Chinmay Raut, Ponnandy Prabhu, Akram Irshaid, Yash Hegde, Yue Chen, Asmita Pant, Antonino Oliveri, Xiaochao Wei, Lishi Yin, Tiffany L Russell, Brian Halligan, Clay F Semenkovich, Elizabeth K Speliotes

2020-Current year OA Pubs

Genetic variants near LYPLAL1 are associated with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) in humans, but their impact on LYPLAL1 function is unknown. We identified LYPLAL1 loss-of-function variants from UK BioBank (UKBB) whole-exome sequencing data that had AlphaMissense or GPN-MSA scores in the top 20% of LYPLAL1 variants for being disruptive. We aggregated these variants and carried out burden analysis for effects on MRI Proton Density-Fat Fraction (MRI-PDFF) and ICD-based MASLD in UKBB. Rare loss-of-function LYPLAL1 variants were associated with reduced MRI-PDFF and ICD diagnosed MASLD across sexes. We used CRISPR to knockout and overexpress LYPLAL1 in human hepatoma cells …

Promoting Community And Social Participation In Chronic Stroke: A Pilot Study Of The Engage Intervention, Elizabeth Skidmore, Carolyn Baum, Jessica Kersey, Emily Kringle, Kelsey Voltz-Poremba, Sular Gordon, Tina Harris, Heidi Fischer, Maureen Gecht, Michelle Furman, Joy Hammel

2020-Current year OA Pubs

BACKGROUND: Survivors of stroke report low levels of community and social participation, even years after stroke. ENGAGE is a community-based intervention that merges social learning, guided problem solving, and supervised practice to collaboratively identify, generate, and apply solutions to challenges with community and social participation after stroke.

OBJECTIVE: We examined the feasibility, acceptability, and safety of ENGAGE and characterized within group changes in community and social participation outcomes.

METHODS: Community-dwelling survivors of stroke, occupational therapy providers, and occupational therapy scientists partnered to co-design the essential and structural elements of ENGAGE, as well as to evaluate ENGAGE using a multi-site single-arm …

Deep Learning In Fetal, Infant, And Toddler Neuroimaging Research, Jenna H Chin, Madeleine K Wyburd, Vladislav Ayzenberg, Laurie Bayet, Berkin Bilgic, Emily M Chen, Yuting Chen, Áine Dineen, Shohei Fujita, Janelle Liu, Yohan Jun, M Catalina Camacho, Lilla Zöllei

2020-Current year OA Pubs

Artificial intelligence (AI) is increasingly being integrated into everyday tasks and work environments. However, its adoption in medical image analysis has progressed more slowly due to high clinical stakes, limited availability of labeled data, and substantial variability in imaging protocols and population. These challenges are further pronounced in the field of fetal, infant, and toddler (FIT) neuroimaging, where datasets are especially scarce and subject to large amounts of anatomical variability. However, deep learning (DL), a specific method within machine learning, which is itself a subfield of AI, has emerged as a powerful framework to adapt to the challenges of medical …

Predictors Of Delayed Recovery In Ambulatory Advanced Endoscopic Procedures, Zoilo K Suarez, Alexandria Lenyo, Philip M Frasse, Derek J Platt, Thomas Hollander, Talwinder Nagi, Michael Dedonno, Vladimir Kushnir, Juan Reyes Genere

2020-Current year OA Pubs

BACKGROUND: There is a scarcity of data evaluating patient-related outcomes of advanced or complex endoscopy (ACE) through the post-anesthesia recovery course. Yet, gastrointestinal distress following ACE can occur commonly, and this may impact recovery length of stay and the approach to post-anesthesia care. This study aimed to describe post-procedural symptoms in patients undergoing ACE and identify factors that influence recovery time and course.

METHODS: We retrospectively reviewed a prospectively collected database of patients who underwent ambulatory ACE. Procedural-related symptoms, recovery time, dismissal rate, and adverse events (AE) were recorded. Factors associated with extended recovery time were analyzed using multiple regression …

Technology-Assisted Total Hip Arthroplasty: A Contemporary Analysis Of Regional Trends, National Trends, And 90-Day Outcomes In A Nationwide Cohort, Amy Y Zhao, Alex Gu, Gireesh Reddy, Bryant M Song, Ilya Bendich, Andrew M Schneider

2020-Current year OA Pubs

BACKGROUND: Technology-assisted total hip arthroplasty (THA)-including computer-navigated and robotic-assisted techniques-has emerged as a strategy to enhance component alignment and potentially improve postoperative outcomes. Although prior studies have described increasing utilization, contemporary trends and associated complication rates remain underexplored.

METHODS: A retrospective cohort study was conducted using a large national database to identify patients who underwent primary elective THA between 2010 and 2023. Patients were stratified into conventional vs technology-assisted THA groups, with the latter defined by the use of computer navigation or robotic assistance. Annual utilization trends were evaluated using linear regression, and 90-day postoperative complications were compared using multivariate …

Acute Myocardial Infarction In Medicare Beneficiaries During And After The Covid-19 Pandemic, Jonah M Graves, R J Waken, Fengxian Wang, Rishi K Wadhera, Jose F Figueroa, E John Orav, Osvaldo J Laurido-Soto, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: During early months of the COVID-19 pandemic, presentations for acute myocardial infarction (AMI) declined significantly, and outcomes worsened. However, the full extent and long-term sequelae of changes in AMI epidemiology during the pandemic remain uncertain, as does whether these patterns differed by rurality.

OBJECTIVE: To describe the epidemiology of AMI-related hospitalizations, interventions, and outcomes among Medicare beneficiaries throughout the COVID-19 pandemic, focusing on differences in urban and rural populations.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included all Medicare fee-for-service beneficiaries with AMI between January 1, 2018, and December 31, 2023, in the analysis. Data were analyzed from …

Clostridioides Difficile Colonization And Infection In Pediatric Oncology And Stem Cell Transplant Patients, Daniel N Willis, Erik R Dubberke, Robert J Hayashi, Phillip I Tarr, David B Haslam, Tiffany Hink, Jingqin Luo, Yu Tao, Amruta Padhye, Erin M Hall, Gregory A Storch

2020-Current year OA Pubs

BACKGROUND: Pediatric oncology and hematopoietic stem cell transplant (HSCT) patients have elevated risk for

METHODS: We retrospectively studied 276 stools longitudinally collected over 34 months from 32 HSCT and 12 oncology patients treated at a single tertiary center. Specimens were cultured for

RESULTS: Baseline cultures were positive in 16 (50%) HSCT patients and 2 (12%) oncology. On subsequent samples, 64% of patients who were initially negative acquired colonization: 8 of 15 (53%) HSCT and 8 of 10 (80%) oncology. Nine clonal strains and 25 multilocus sequence types were identified by whole genome sequencing, with 4 clones found in both cohorts. …

Relationship Between Clostridioides Difficile Stool Concentration, Nucleic Acid Amplification Test Results, And Environmental Contamination, Mary Morgan Lee, Kimberly A Reske, Tiffany Hink, Skye R S Fishbein, Erin P Newcomer, Candice Cass, Margaret A Olsen, Gautam Dantas, Carey-Ann D Burnham, Erik R Dubberke

2020-Current year OA Pubs

We compared rectal swab nucleic acid amplification testing (NAAT) with stool culture to detect

Exploring Early Antifungal Activity Of Rezafungin As A Stepping-Stone For Shorter Treatment Duration For Candidemia: Pooled Analysis Of 2 Randomized Trials, Luis Ostrosky-Zeichner, Jalal A Aram, Mark Redell, George R Thompson, Oliver A Cornely, James A Mckinnell, Andrej Spec, Peter G Pappas

2020-Current year OA Pubs

BACKGROUND: Guidelines recommend ≥2 weeks of antifungal therapy after candidemia clearance and for invasive candidiasis (IC). This post-hoc analysis evaluates Day 7 pooled data from the phase 2 STRIVE and phase 3 ReSTORE trials to explore early antifungal activity.

METHODS: Adults with candidemia and/or IC received weekly rezafungin 400/200 mg or daily caspofungin 70/50 mg for ≤4 weeks. Efficacy was evaluated in the modified intent-to-treat population via all-cause mortality (ACM; primary endpoint; 20% noninferiority margin), mycological eradication, and time to negative blood culture (TTNBC) at days 7, 14, and 30 (TTNBC assessed only in patients with candidemia). Day 7 safety …

Use Of Inverse Probability Weighting In Cardiovascular Surgical Outcomes Research: Principles, Limitations, And Recommendations, Zhongjian Liu, Wei-Guo Ma, Lei Liu, Prashanth Vallabhajosyula, Haibo Wang

2020-Current year OA Pubs

This statistical primer presents a comprehensive introduction to the use of inverse probability of treatment weighting (IPTW), a method for rebalancing group confounders at baseline in cardiovascular surgical outcomes research. We leveraged a retrospective study comparing the outcomes of 2 different surgical approaches to aortic arch pathology to illustrate the essential aspects of performing IPTW, including basic theories, application, extreme weights, underestimated variance, heterogeneity of treatment effect, and multicollinearity. The limitations of IPTW were discussed with examples of solutions. Ten practical recommendations are made on avoiding the pitfalls in the use of IPTW. Proper use of IPTW may effectively reduce …

Visual Recognition Of The Anteroposterior Female Body Axis Drives Spatial Elements Of Male Courtship In Drosophila, Ross M Mckinney, Christian Monroy Hernandez, Yehuda Ben-Shahar

2020-Current year OA Pubs

Drosophila males exhibit a highly stereotypic courtship ritual toward virgin females, which is comprised of a sequence of specific behavioral elements that depend on inputs from diverse sensory modalities. Particularly, the visual system of the male plays an important role in detecting salient patterns, colors, and motion cues from conspecifics, which can promote or inhibit specific aspects of male courtship such as chase and song production. Here, we use a computer vision and machine learning-based approach, with a simplified courtship paradigm, to show that males also depend on visual cues to determine the anterior-posterior body axis of females, which drives …

Hepatitis C Virus Testing In Perinatally Exposed Children, Rachel L Epstein, Sarah Munroe, Elizabeth A Erdman, Amy Bettano, Megan R Curtis, Laura White, Elisha M Wachman, Anthony Osinski, Alexander Y Walley, Benjamin P Linas

2020-Current year OA Pubs

IMPORTANCE: Despite rising hepatitis C virus (HCV) incidence in pregnant people, studies demonstrate that fewer than 50% of perinatally exposed infants receive HCV testing. Few studies report treatment of infected infants or factors affecting testing.

OBJECTIVE: To identify birthing parent and child factors associated with appropriate HCV testing for perinatally exposed infants and characterize HCV care for children with HCV.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included records on testing, care, and treatment for Massachusetts children perinatally exposed to HCV between 2014 and 2021 from a statewide health database linking statewide vital statistics, infectious disease surveillance data, substance use …

Mda5-Mavs And Interferon-Lambda Signaling In The Intestinal Epithelium Limit Murine Astrovirus Infection, Heyde Makimaa, Harshad Ingle, Leran Wang, Somya Aggarwal, Hongju Deng, Elizabeth A Kennedy, Lynne Foster, Yuhao Li, Megan T Baldridge

2020-Current year OA Pubs

Human astroviruses (HAstVs) are a global cause of pediatric gastroenteritis and can cause disseminated infection in immunocompromised hosts. Murine astrovirus (muAstV) causes acute asymptomatic infections in immunocompetent mice and chronic infection in immunodeficient models and has provided important insights into AstV pathogenesis in vivo. MuAstV can protect immunodeficient mice from other enteric viruses via robust induction of antiviral cytokine interferon-lambda (IFN-λ), with recent findings implicating goblet cells and enterocytes as both cell types infected by muAstV as well as potential sources of IFN-λ in vivo. However, the viral sensing pathways that regulate induction of IFN-λ, as well as the specific …

Glp-1 Receptor Agonists Or Sglt2 Inhibitors And Nonarteritic Anterior Ischemic Optic Neuropathy, Taeyoung Choi, Ziyad Al-Aly, Yan Xie

2020-Current year OA Pubs

No abstract provided.

Exploring Nurses' Documentation Prioritization Strategies To Alleviate Ehr Documentation Burden: A Phenomenological Study, Rosemary Mugoya, Jennifer Thate, Fan Hao, Sarah C Rossetti, Po-Yin Yen

2020-Current year OA Pubs

OBJECTIVE: This study aims to understand how inpatient nurses determine and prioritize necessary documentation within the context of the Excessive Documentation Burden (ExDocBurden) in Electronic Health Records (EHRs).

METHODOLOGY: A phenomenological approach was used to explore inpatient nurses' lived experiences of prioritizing EHR documentation. Interpretive phenomenology guided the study design, focusing on how nurses prioritize documentation. Purposive sampling recruited 14 registered nurses (RNs) from acute and critical care settings. Data was collected through semi-structured interviews and analyzed using Colaizzi's 7-step and Smith's Interpretive Phenomenology Analysis.

RESULTS: Five themes emerged: (1) Advocating for Quality Patient Care Environment and Patient Needs, (2) …

Automating Evaluation Of Llm-Generated Responses To Patient Questions About Rare Diseases, Min Zhao, Inez Y Oh, Aditi Gupta, Sally Cohen-Cutler, Kathryn M Harmoney, Albert M Lai, Bryan A Sisk

2020-Current year OA Pubs

OBJECTIVES: Patients with rare diseases often struggle to find accurate medical information, and large language model (LLM)-based chatbots may help meet this need. However, evaluating LLM-generated free-text answers typically requires physician review, which is time-consuming and difficult to scale. This study compared traditional natural language processing (NLP) metrics to emerging LLM-based evaluation approaches for assessing answer quality in the context of Complex Lymphatic Anomalies (CLAs).

MATERIALS AND METHODS: We compiled 25 common patients' questions about CLAs and generated 175 responses to these questions from seven LLMs. Three expert physicians scored these responses for accuracy. We compared these physician-assigned scores with …

Multicenter Evaluation Of Ceftazidime/Avibactam In Pediatric Patients Across The United States: Real-World Insights Into The Management Of Drug-Resistant Gram-Negative Infections, Taylor Morrisette, Christine R Lockowitz, Valerie Yuenger, Evan E Facer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Antimicrobial resistance among gram-negative pathogens is a global threat, with children particularly vulnerable due to limited treatment options and age-specific clinical outcomes data. Ceftazidime/avibactam (CZA) is effective against resistant gram-negative bacteria and demonstrates high success rates in adults; however, pediatric data remain limited. This study examined CZA use in children across United States medical centers.

METHODS: This multicenter, retrospective, observational cohort study included pediatric patients (< 18 years) who received ≥48 hours of CZA for suspected or confirmed gram-negative infections between February 2015 and October 2023. The primary outcome was clinical success, defined as occurrence of all 3 components: (1) absence of all-cause mortality within 30 days of CZA initiation, (2) absence of microbiologic and clinical recurrence within 30 days of CZA discontinuation, and (3) resolution or improvement of infection-related signs and symptoms during CZA therapy without modification of therapy due to clinical failure. Secondary outcomes included adverse events attributable to CZA and resistance development to CZA.

RESULTS: One-hundred patients were included, with most receiving CZA for targeted therapy (67%). The median (IQR) age and weight were 9.8 (1.9-15.9) years and 24.2 (12.2-49.9) kg, respectively. Nearly all patients (88%) had …

Neurofibromatosis Type 1-Plexiform Neurofibromas: Integrating Treatment Across Pediatric And Adult Populations, Amy E Armstrong, Andrea M Gross, Laura J Klesse, Steven D Rhodes, Shivani Ahlawat, Verena Staedtke, Camilo A Molina, Angela C Hirbe

2020-Current year OA Pubs

Plexiform neurofibromas (PNs) are a hallmark of neurofibromatosis type 1 (NF1), affecting ∼50% of individuals with the condition. Originating from Schwann cells and other peripheral nerve sheath components, these tumors can cause significant morbidity, including functional impairment, diminished health-related quality of life, chronic pain, and malignant transformation. Managing NF1-PNs is challenging because of disease variability, differing growth rates, and age-related differences in clinical presentation and treatment tolerability. This review examines current therapeutic strategies, including surgery, medical therapies, and emerging treatments, emphasizing individualized care. Highlighted here is the need for age-specific treatment planning, particularly as disease progression, comorbidities, and side-effect profiles …

An International Mega-Analysis Of Psychedelic Drug Effects On Brain Circuit Function, Manesh Girn, Nico Dosenbach, Et Al.

2020-Current year OA Pubs

Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented and sometimes inconsistent findings. Here, to help facilitate greater convergence, we conducted a 'mega-analysis' integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries. By applying a uniform preprocessing pipeline and …

Metabolically Reprogrammed Eosinophils Impair T Cell Immunity And Cause Chronic Skin Infection, David Barinberg, Heidi Sebald, Tobias Gold, Baplu Rai, Daniel Radtke, Dominik Lerm, David Voehringer, Jonathan Jantsch, Stefan Wirtz, Alina Ulezko Antonova, Marco Colonna, Christian Bogdan, Ulrike Schleicher

2020-Current year OA Pubs

Eosinophils exhibit antimicrobial, cytotoxic and immunoregulatory effects, but our knowledge of their transcriptional and functional heterogeneity is still limited, especially in non-intestinal tissues. Here, we used a mouse model of chronic cutaneous inflammation elicited by the protozoan pathogen Leishmania mexicana to investigate the function and transcriptional dynamics of skin eosinophils. Infection of C57BL/6 mice triggered local and systemic eosinophilia that was driven by type 2 innate lymphoid cells and interleukin-5. Genetic and pharmacological eosinophil depletion led to an enhanced Th1 response, polarization towards M1-like macrophages and resolution of clinical disease, despite an unexpected simultaneous upregulation of IL-4. Single-cell transcriptomics revealed …