tbuckley/cabot-search huggingface dataset:
Dual neutralization of influenza virus hemagglutinin and neuraminidase by a bispecific antibody leads to improved antiviral activity
Authors: Romila Moirangthem, Sapir Cordela, Dina Khateeb, Ben Shor, Ivan Kosik, Dina Schneidman-Duhovny, Michal Mandelboim, Friederike Jönsson, Jonathan W. Yewdell, Timothée Bruel, Yotam Bar-On
Journal: Molecular Therapy (2024)

Targeting multiple viral proteins is pivotal for sustained suppression of highly mutable viruses. In recent years, broadly neutralizing antibodies that target the influenza virus hemagglutinin and neuraminidase glycoproteins have been developed, and antibody monotherapy has been tested in preclinical and clinical studies to treat or prevent influenza virus infection. However, the impact of dual neutralization of the hemagglutinin and neuraminidase on the course of infection, as well as its therapeutic potential, has not been thoroughly tested. For this purpose, we generated a bispecific antibody that neutralizes both the hemagglutinin and the neuraminidase of influenza viruses. We demonstrated that this bispecific antibody has a dual-antiviral activity as it blocks infection and prevents the release of progeny viruses from the infected cells. We show that dual neutralization of the hemagglutinin and the neuraminidase by a bispecific antibody is advantageous over monoclonal antibody combination as it resulted an improved neutralization capacity and augmented the antibody effector functions. Notably, the bispecific antibody showed enhanced antiviral activity in influenza virus-infected mice, reduced mice mortality, and limited the virus mutation profile upon antibody administration. Thus, dual neutralization of the hemagglutinin and neuraminidase could be effective in controlling influenza virus infection.
Trainee participation and outcomes in high-risk ERCP: a secondary analysis of the Stent versus Indomethacin trial
Authors: Sachin Wani, Jingwen Zhang, Lydia D. Foster, Valerie Durkalski-Mauldin, B. Joseph Elmunzer, Jose Serrano, Gregory A. Coté, Steven A. Edmundowicz, Raj Shah, Ji Young Bang, Shyam Varadarajulu, Vikesh K. Singh, Mouen Khashab, Richard S. Kwon, James M. Scheiman, Field F. Willingham, Steven A. Keilin, Georgios I. Papachristou, Amitabh Chak, Adam Slivka, Daniel Mullady, Vladimir Kushnir, James Buxbaum, Rajesh Keswani, Timothy B. Gardner, Nauzer Forbes, Amit Rastogi, Andrew Ross, Joanna Law, Patrick Yachimski, Yen-I Chen, Alan Barkun, Zachary L. Smith, Bret Petersen, Andrew Y. Wang, John R. Saltzman, Rebecca L. Spitzer, Jazmyne Gallegos, Case Brennan, Collins Ordiah, Cathie Spino
Journal: Clinical Gastroenterology and Hepatology (2024)
Armored Bicistronic CAR T Cells with Dominant-negative TGF-β Receptor II to Overcome Resistance in Glioblastoma
Authors: Nannan Li, Jesse L Rodriguez, Yibo Yin, Meghan T Logun, Logan Zhang, Shengkun Yu, Kelly A Hicks, Jiasi Vicky Zhang, Laura Zhang, Chuncheng Xie, Jiabin Wang, Tianyu Wang, Jiayi Xu, Joseph A Fraietta, Zev A Binder, Zhiguo Lin, Donald M O'Rourke
Journal: Molecular Therapy (2024)
Live Rotavirus Vaccination Appears Low-risk in Infants Born to Mothers With Inflammatory Bowel Disease on Biologics
Authors: Kenneth Ernest-Suarez, Luis E Murguía-Favela, Cora Constantinescu, Tiffany Fitzpatrick, Karina A Top, Jia Hu, Taj Jadavji, Yvette Leung, Melissa Chan, Remo Panaccione, Cynthia H Seow
Journal: Clinical Gastroenterology and Hepatology (2024)

Background & AimsBiologic therapies in the context of inflammatory bowel disease and pregnancy lead to improved maternal and fetal outcomes. Placental transfer results in detectable drug concentrations in infants. Rotavirus infection results in diarrheal related hospitalizations; however, the live oral vaccine is not currently recommended in biologic exposed infants. The aim of this study was to assess the effect of maternal biologic therapies on the infant immune system and safety of live rotavirus vaccination in biologic-exposed infants.MethodsBiologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing (complete blood count, differential, immunoglobulin levels, extended B-cell and T-cell subset enumeration, Recent Thymic Emigrants, regulatory T-cell numbers, mitogen stimulation assays, and review of T-cell Receptor Excision Circles in the newborn screen). Rotavirus vaccine-specific adverse effects following immunizations up to 42 days post the last dose of the vaccine series were recorded.ResultsThere were 57 infants born to 52 mothers with inflammatory bowel disease exposed to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester for a median of 39 weeks (interquartile range, 38–39 weeks) at delivery. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 ug/mL (range, 0.4–28.8 ug/mL), adalimumab concentrations of 1.7 ug/mL (range, 0.7–7.9 ug/mL), ustekinumab concentrations of 0.6 ug/mL (range, 0–1.1), and undetectable for vedolizumab at 10.7 weeks (interquartile range, 9.4–12.4) of age. The live oral rotavirus vaccine series was provided to 50 infants with the first dose given at a median of 13 weeks of age. No adverse effects following immunization were reported.ConclusionImmune function testing was normal, and administration of live rotavirus vaccination appeared low-risk in biologic-exposed infants irrespective of circulating drug levels.Graphical abstract
Tumor intrinsic CDC42BPB confers resistance to anti-PD-1 immune checkpoint blockade in breast cancer
Authors: Ravindra Pramod Deshpande, Kerui Wu, Shih-Ying Wu, Abhishek Tyagi, Eleanor C Smith, John Hunting, Jimmy Ruiz, Wencheng Li, Kounosuke Watabe
Journal: Molecular Therapy (2024)
Development and IND-enabling studies of a novel Cas9 genome-edited autologous CD34+ cell therapy to induce fetal hemoglobin for sickle cell disease
Authors: Varun Katta, Kiera O’Keefe, Yichao Li, Thiyagaraj Mayuranathan, Cicera R. Lazzarotto, Rachael K. Wood, Rachel M. Levine, Alicia Powers, Kalin Mayberry, Garret Manquen, Yu Yao, Jingjing Zhang, Yoonjeong Jang, Nikitha Nimmagadda, Erin A. Dempsey, GaHyun Lee, Naoya Uchida, Yong Cheng, Frank Fazio, Tim Lockey, Mike Meagher, Akshay Sharma, John F. Tisdale, Sheng Zhou, Jonathan S. Yen, Mitchell J. Weiss, Shengdar Q. Tsai
Journal: Molecular Therapy (2024)

Sickle cell disease (SCD) is a common, severe genetic blood disorder. Current pharmacotherapies are partially effective and allogeneic hematopoietic stem cell transplantation is associated with immune toxicities. Genome editing of patient hematopoietic stem cells (HSCs) to reactivate fetal hemoglobin (HbF) in erythroid progeny offers an alternative potentially curative approach to treat SCD. Although the FDA released guidelines for evaluating genome editing risks, it remains unclear how best to approach pre-clinical assessment of genome-edited cell products. Here, we describe rigorous pre-clinical development of a therapeutic γ-globin gene promoter editing strategy that supported an investigational new drug application cleared by the FDA. We compared γ-globin promoter and BCL11A enhancer targets, identified a potent HbF-inducing lead candidate, and tested our approach in mobilized CD34
A novel strategy for performing endoscopic submucosal dissection for circumferential superficial esophageal neoplastic lesions with kissing traction
Authors: Ben-hua Wu, Li-sheng Wang, Zheng-lei Xu
Journal: Endoscopy (2024)

Endoscopic submucosal dissection (ESD) is a widely utilized procedure for early esophageal cancer and precancerous lesions. However, it remains technically challenging and time consuming for circumferential lesions. Numerous studies have utilized various techniques for improving the efficacy of ESD in the treatment of esophageal circumferential lesions [1] [2] [3]. Herein, we propose a novel approach for improving ESD for esophageal peripheral lesions, termed the "kissing traction technique" (KT-ESD).
Gel immersion technique in interventional endoscopic ultrasound for pancreatobiliary lesions
Authors: Haruka Toyonaga, Tsuyoshi Hayashi, Kazuki Hama, Toshifumi Kin, Masayo Motoya, Kuniyuki Takahashi, Akio Katanuma
Journal: Endoscopy (2024)

Interventional endoscopic ultrasound (iEUS), including EUS-guided tissue acquisition (EUS-TA) and biliary drainage (EUS-BD), plays a crucial role in the assessment and treatment of pancreaticobiliary lesions. Yet, iEUS presents challenges due to anatomical factors, posing a risk of serious complications. For observational pancreaticobiliary EUS, studies have shown that utilizing a high viscosity gel (Viscoclear; Otsuka Pharmaceutical, Tokushima, Japan) instead of water to fill the duodenal lumen yields clearer EUS images and effectively maintains the luminal dilatation for an extended period [1] [2] [3]. Recently, a handful of reports have explored the gel immersion technique within iEUS [4] [5]. Here, we evaluate the effectiveness and safety of the gel immersion method, particularly in EUS-TA and EUS-BD ([Video 1]).
Venous Thromboembolism Prophylaxis in High-Risk Pediatric Trauma Patients
Authors: Amanda B. Witte, Kyle Van Arendonk, Carisa Bergner, Martin Bantchev, Richard A. Falcone, Suzanne Moody, Heather A. Hartman, Emily Evans, Rajan Thakkar, Kelli N. Patterson, Peter C. Minneci, Grace Z. Mak, Mark B. Slidell, MacKenton Johnson, Matthew P. Landman, Troy A. Markel, Charles M. Leys, Linda Cherney Stafford, Jessica Draper, David S. Foley, Cynthia Downard, Tracy M. Skaggs, Dave R. Lal, David Gourlay, Peter F. Ehrlich
Journal: JAMA Surgery (2024)

The indications, safety, and efficacy of chemical venous thromboembolism prophylaxis (cVTE) in pediatric trauma patients remain unclear. A set of high-risk criteria to guide cVTE use was recently recommended; however, these criteria have not been evaluated prospectively.
CircCHSY1 protects hearts against ischaemia/reperfusion injury by enhancing heme oxygenase 1 expression via miR-24-3p
Authors: Jiliang Tan, Jie Min, Yun Jiang, Shenyan Liu, Minxia Ke, Zhinong Wang, Huang-Tian Yang
Journal: Cardiovascular Research (2024)

Abstract Aims Circular RNAs (circRNAs) are important players involved in a variety of physiological and pathological processes. However, their functions and mechanisms during myocardial ischaemic injury and protection remain largely unknown. We recently found significant alterations of many circRNAs including circCHSY1 following myocardial ischaemia/reperfusion (I/R) injury, whereas their exact functions are unclear. Here, we investigated the roles of circCHSY1 in the acute myocardial I/R injury and the potential mechanisms involved. Methods and results The expression of circCHSY1 was detected in cardiomyocytes from mouse, rat, and human embryonic stem cells (hESC-CMs). It was further up-regulated in mouse I/R (30 min/24 h) hearts, oxygen glucose deprivation/reperfusion (OGD/R, 6 h/2 h) primary neonatal rat ventricular cardiomyocytes (NRCMs) and OGD/R (48 h/2 h) hESC-CMs. Adenovirus-mediated circCHSY1 overexpression significantly decreased infarct size and lactate dehydrogenase (LDH) release in mouse I/R hearts. Consistently, circCHSY1 overexpression reduced the LDH release in the OGD/R NRCMs and hESC-CMs, improved cell viability, and preserved mitochondrial function in the OGD/R NRCMs, whereas there were no significant differences in cell viability and LDH release between the OGD/R NRCMs with and without small interfering RNA (siRNA)-mediated circCHSY1 knockdown. Mechanistically, circCHSY1 was detected to bind with miR-24-3p analysed by dual-luciferase assay and RNA pull-down assays. CircCHSY1 overexpression-mediated protective effects on cells and mitochondria in OGD/R NRCMs were reversed by the miR-24-3p mimic. Furthermore, dual-luciferase assay showed that miR-24-3p was directly bound to heme oxygenase 1 (HO1) via its 3′UTR. The protein level of HO1 was down-regulated by miR-24-3p mimic in OGD/R NRCMs but enhanced by the circCHSY1 overexpression in vitro and in vivo. Functionally, the HO1 knockdown by adenovirus in vivo and by siRNA in vitro eliminated cardioprotective effects of circCHSY1 overexpression. Conclusion CircCHSY1 is up-regulated following myocardial I/R injury. The higher level of circCHSY1 protects I/R hearts and cardiomyocytes. The protection of circCHSY1 is mediated through enhancement of the HO1 level, resulting in preserving mitochondrial homoeostasis via targeting miR-24-3p in cardiomyocytes. These findings suggest circCHSY1 as a protective factor.
A comparative analysis of IDH-mutant glioma in pediatric, young adult, and older adult patients
Authors: Mary Jane Lim-Fat, Jennifer A Cotter, Mehdi Touat, Jayne Vogelzang, Cecilia Sousa, Will Pisano, Jack Geduldig, Varun Bhave, Joseph Driver, Pei-Chi Kao, Alana McGovern, Clement Ma, Ashley S Margol, Kristina Cole, Amy Smith, Stewart Goldman, Kristiyana Kaneva, AiLien Truong, Kellie J Nazemi, Matthew D Wood, Karen D Wright, Wendy B London, Katherine E Warren, Patrick Y Wen, Wenya Linda Bi, Sanda Alexandrescu, David A Reardon, Keith L Ligon, Kee Kiat Yeo
Journal: Neuro-Oncology (2024)

Abstract Background The frequency and significance of IDH mutations in glioma across age groups are incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes. Methods Clinical, histologic, and sequencing data from patients with IDH-mutant, grades 2–4 gliomas, were collected from collaborating institutions between 2013 and 2019. Patients were categorized as pediatric (&amp;lt;19 years), young adult (YA; 19–39 years), or older adult (≥40 years). Clinical presentation, treatment, histologic, and molecular features were compared across age categories using Fisher’s exact test or analysis-of-variance. Cox proportional-hazards regression was used to determine the association of age and other covariates with overall (OS) and progression-free survival (PFS). Results We identified a cohort of 379 patients (204 YA) with IDH-mutant glioma with clinical data. There were 155 (41%) oligodendrogliomas and 224 (59%) astrocytomas. YA showed significantly shorter PFS and shorter median time-to-malignant transformation (MT) compared to pediatric and adult groups, but no significant OS difference. Adjusting for pathology type, extent of resection, and upfront therapy in multivariable analysis, the YA group was independently prognostic of shorter PFS than pediatric and adult groups. Among astrocytomas, CDK4/6 copy number amplifications were associated with both shorter PFS and shorter OS. Among oligodendrogliomas, PIK3CA and CDKN2A/2B alterations were associated with shorter OS. Conclusions IDH-mutant glioma YA patients had significantly shorter PFS and time to MT but did not differ in OS compared to pediatric and adult groups. Treatment approaches varied significantly by patient age and warrant further study as addressable age-associated outcome drivers.
Temozolomide Use in Elderly Patients with MGMT Promoter Unmethylated Glioblastoma: Is It Finally Time to Dismount a Dead Horse?
Authors: Ugur T Sener, Erik P Sulman, Jann N Sarkaria
Journal: Neuro-Oncology (2024)

Journal Article Corrected proof Temozolomide use in elderly patients with MGMT promoter unmethylated glioblastoma: Is it finally time to dismount a dead horse? Get access Ugur T Sener, Ugur T Sener Department of Neurology, Mayo Clinic, Rochester, Minnesota, USADepartment of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Erik P Sulman, Erik P Sulman Department of Radiation Oncology, NYU Grossman School of Medicine, New York, New York, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Jann N Sarkaria Jann N Sarkaria Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA Corresponding Author: Jann N. Sarkaria, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA (Sarkaria.Jann@mayo.edu). Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae143, https://doi.org/10.1093/neuonc/noae143 Published: 31 July 2024 Article history Published: 31 July 2024 Corrected and typeset: 20 August 2024
GLP-1 Agonists for Obesity
Authors: Alyssa J. Moran, Christina A. Roberto
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effects of phospholipid type and particle size on lipid nanoparticle distribution in vivo and in pancreatic islets
Authors: Takayuki Oguma, Takanori Kanazawa, Yukiko K Kaneko, Ren Sato, Miku Serizawa, Akira Ooka, Momoka Yamaguchi, Tomohisa Ishikawa, Hiromu Kondo
Journal: Journal of Controlled Release (2024)
Imaging the cerebral vasculature at different scales: translational tools to investigate the neurovascular interfaces
Authors: Lorenzo Carnevale, Giuseppe Lembo
Journal: Cardiovascular Research (2024)

Abstract The improvements in imaging technology opened up the possibility to investigate the structure and function of cerebral vasculature and the neurovascular unit with unprecedented precision and gaining deep insights not only on the morphology of the vessels but also regarding their function and regulation related to the cerebral activity. In this review, we will dissect the different imaging capabilities regarding the cerebrovascular tree, the neurovascular unit, the haemodynamic response function, and thus, the vascular–neuronal coupling. We will discuss both clinical and preclinical setting, with a final discussion on the current scenery in cerebrovascular imaging where magnetic resonance imaging and multimodal microscopy emerge as the most potent and versatile tools, respectively, in the clinical and preclinical context.
Leadless Ultrasound-Based Cardiac Resynchronization Therapy
Authors: Fred M. Kusumoto
Journal: JAMA Cardiology (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Immune and gene-expression profiling in estrogen receptor low and negative early breast cancer
Authors: Davide Massa, Claudio Vernieri, Lorenzo Nicolè, Carmen Criscitiello, Florence Boissière-Michot, Séverine Guiu, Angélique Bobrie, Gaia Griguolo, Federica Miglietta, Andrea Vingiani, Riccardo Lobefaro, Beatrice Taurelli Salimbeni, Claudia Pinato, Francesca Schiavi, Silvia Brich, Carlo Pescia, Nicola Fusco, Giancarlo Pruneri, Matteo Fassan, Giuseppe Curigliano, Valentina Guarneri, William Jacot, Maria Vittoria Dieci
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background The cutoff of &amp;lt;1% positive cells to define estrogen receptor (ER) negativity by immunohistochemistry (IHC) in breast cancer (BC) is debated. We explored the tumor immune microenvironment and gene-expression profile of patients with early-stage HER2-negative ER-low (ER 1%-9%) BC, comparing them to ER-negative (ER &amp;lt;1%) and ER-intermediate (ER 10%-50%) tumors. Methods Among 921 patients with early-stage I-III, ER ≤50%, HER2-negative BCs, tumors were classified as ER-negative (n = 712), ER-low (n = 128), or ER-intermediate (n = 81). Tumor-infiltrating lymphocytes (TILs) were evaluated. CD8+, FOXP3+ cells, and PD-L1 status were assessed by IHC and quantified by digital pathology. We analyzed 776 BC-related genes in 116 samples. All tests were 2-sided at a &amp;lt;.05 significance level. Results ER-low and ER-negative tumors exhibited similar median TILs, statistically significantly higher than ER-intermediate tumors. CD8/FOXP3 ratio and PD-L1 positivity rates were comparable between ER-low and ER-negative groups. These groups showed similar enrichment in basal-like intrinsic subtypes and comparable expression of immune-related genes. ER-low and ER-intermediate tumors showed significant transcriptomic differences. High TILs (≥30%) were associated with improved relapse-free survival (RFS) in ER-low (5-year RFS 78.6% vs 66.2%, log-rank P = .033, hazard ratio [HR] 0.37 [95% CI = 0.15 to 0.96]) and ER-negative patients (5-year RFS 85.2% vs 69.8%, log-rank P &amp;lt; .001, HR 0.41 [95% CI = 0.27 to 0.60]). Conclusions ER-low and ER-negative tumors are similar biological and molecular entities, supporting their comparable clinical outcomes and treatment responses, including to immunotherapy. Our findings contribute to the growing evidence calling for a reevaluation of ER-positive BC classification and management, aligning ER-low and ER-negative tumors more closely.
Spiky tubular nanoparticles with low protein corona can realize efficient and non-destructive penetration through endothelial barrier
Authors: Yuan Huang, Dong Ye, Xiaojing Liu, Hao Chen, Xinxin Luo, Bo Huang, Nayuan Zhou, Hangxing Wang, Qichao Zou, Senbiao Fang, Suxiao Wang, Limin Wu
Journal: Journal of Controlled Release (2024)