tbuckley/cabot-search huggingface dataset:
MicroRNA-210 Controls Mitochondrial Metabolism and Protects Heart Function in Myocardial Infarction
Authors: Rui Song, Chiranjib Dasgupta, Cassidy Mulder, Lubo Zhang
Journal: Circulation (2022)

Background: Ischemic heart disease remains a leading cause of death worldwide. In this study, we test the hypothesis that microRNA-210 protects the heart from myocardial ischemia-reperfusion (IR) injury by controlling mitochondrial bioenergetics and reactive oxygen species (ROS) flux. Methods: Myocardial infarction in an acute setting of IR was examined through comparing loss- versus gain-of-function experiments in microRNA-210–deficient and wild-type mice. Cardiac function was evaluated by echocardiography. Myocardial mitochondria bioenergetics was examined using a Seahorse XF24 Analyzer. Results: MicroRNA-210 deficiency significantly exaggerated cardiac dysfunction up to 6 weeks after myocardial IR in male, but not female, mice. Intravenous injection of microRNA-210 mimic blocked the effect and recovered the increased myocardial IR injury and cardiac dysfunction. Analysis of mitochondrial metabolism revealed that microRNA-210 inhibited mitochondrial oxygen consumption, increased glycolytic activity, and reduced mitochondrial ROS flux in the heart during IR injury. Inhibition of mitochondrial ROS with MitoQ consistently reversed the effect of microRNA-210 deficiency. Mechanistically, we showed that mitochondrial glycerol-3-phosphate dehydrogenase is a novel target of microRNA-210 in the heart, and loss-of-function and gain-of-function experiments revealed that glycerol-3-phosphate dehydrogenase played a key role in the microRNA-210–mediated effect on mitochondrial metabolism and ROS flux in the setting of heart IR injury. Knockdown of glycerol-3-phosphate dehydrogenase negated microRNA-210 deficiency–induced increases in mitochondrial ROS production and myocardial infarction and improved left ventricular fractional shortening and ejection fraction after the IR treatment. Conclusions: MicroRNA-210 targeting glycerol-3-phosphate dehydrogenase controls mitochondrial bioenergetics and ROS flux and improves cardiac function in a murine model of myocardial infarction in the setting of IR injury. The findings suggest new insights into the mechanisms and therapeutic targets for treatment of ischemic heart disease.
Authors’ Reply to the Letter to the Editor by Daniel M. Green
Authors: Jeffrey S. Dome, Elizabeth A. Mullen, David B. Dix, Eric J. Gratias, Peter F. Ehrlich, Najat C. Daw, James I. Geller, Murali Chintagumpala, Geetika Khanna, John A. Kalapurakal, Lindsay Renfro, Elizabeth J. Perlman, Paul E. Grundy, Conrad V. Fernandez
Journal: Journal of the National Comprehensive Cancer Network (2022)

designed, randomized studies.
Short-term Outcomes of Corticosteroid Monotherapy in Multisystem Inflammatory Syndrome in Children
Authors: D. Sofia Villacis-Nunez, Kaitlin Jones, Aysha Jabbar, Lucie Fan, Whitney Moore, Andrew S. Peter, Michaela Henderson, Yijin Xiang, Michael S. Kelleman, Whitney Sherry, Shanmuganathan Chandrakasan, Matthew E. Oster, Preeti Jaggi, Sampath Prahalad
Journal: JAMA Pediatrics (2022)

Optimal agents and duration of primary treatment for multisystem inflammatory syndrome in children (MIS-C) remain unclear.To compare short-term patient outcomes based on initial treatment with corticosteroids, intravenous immunoglobulin (IVIG), or both.This retrospective cohort study included patients in a tertiary-care pediatric hospital system who had MIS-C per the Centers for Disease Control and Prevention case definition during the period March 2020 to February 2021.Immunomodulatory therapy within the first 24 hours (patients in the intensive care unit [ICU]) or 48 hours (non-ICU patients): corticosteroids alone, IVIG alone, and IVIG plus corticosteroids.Primary outcome was failure of initial therapy, defined as therapy escalation due to fever or worsening or lack of improvement of laboratory, cardiac, or noncardiac clinical factors after 24 hours (ICU patients) or 48 hours (non-ICU patients) from time of therapy initiation, per clinician assessment. Secondary outcomes included presence of complications, cardiovascular outcomes, fever duration, length of hospital and ICU stays, corticosteroid use duration, and need for readmission.Among 228 eligible patients, 215 patients were included in the univariate analysis; median age was 8 years, and 135 (62.8%) were boys. There were 69 patients in the corticosteroids group, 31 patients in the IVIG group, and 115 patients in the IVIG plus corticosteroids group. Patients in the corticosteroids group had milder disease at presentation. After propensity score weighting including 179 patients (68 in the corticosteroids group and 111 in the IVIG plus corticosteroids group), rates of initial treatment failure were similar between groups. Among patients whose initial treatment failed, treatment failure in the IVIG plus corticosteroids group was more likely to be based on laboratory parameters (odds ratio [OR], 1.96; 95% CI, 1.07-3.60) and less likely to be based on cardiovascular markers (OR, 0.39; 95% CI, 0.2-0.76), per clinician assessment. Patients in the IVIG plus corticosteroids group had a longer median inpatient stay (6 vs 5 days; P = .001) and longer median corticosteroid course duration (10 vs 5 days; P = .04) compared with the corticosteroids group. Forty-nine patients (71% of 69 in the corticosteroids group) recovered after receiving corticosteroid monotherapy for 10 days or less.Corticosteroid monotherapy is a reasonable management option for a subset of patients with MIS-C, particularly those with mild disease.
Targeting CD96 overcomes PD-1 blockade resistance by enhancing CD8+ TIL function in cervical cancer
Authors: Yumeng Wang, Congwen Wang, Junjun Qiu, Xinyu Qu, Jing Peng, Chong Lu, Meng Zhang, Mingxing Zhang, Xingling Qi, Guiling Li, Keqin Hua
Journal: Journal for ImmunoTherapy of Cancer (2022)

Novel therapies are needed to treat recurrent and advanced cervical cancer (CC), as their prognosis remains very poor. Although therapies targeting the programmed cell death protein 1 (PD-1) pathway have been approved for CC, a large subset of patients exhibit innate resistance. Using checkpoint inhibitors in combination could enhance their efficacy.Blood samples, tumor specimens, and peritumorous (PT) tissues were obtained from patients with CC. The inhibitory receptor expression and phenotypical analysis of CD8+ T cells in CC specimens were analyzed by flow cytometry. The ligands of CD96 expressed by tumor cells were measured by immunohistochemistry and immunofluorescence. Sensitivity to pembrolizumab was evaluated by an ex vivo treatment assay based on the single-cell culture of CC specimens. The efficacies of PD-1 and/or CD96 blockades were explored using an ex vivo treatment assay and an human papillomavirus-positive TC-1 xenograft mouse model in vivo.We found that CD96 expression was elevated on CD8+ tumor-infiltrating lymphocytes (TILs) from patients with CC who were insensitive to the PD-1 blockade. These CD96-expressing CD8+ TILs often coexpressed PD-1. The ratio of the CD96+CD8+/CD96-CD8+ T-cell gene signature from the scRNA-seq data was significantly associated with the poor survival of patients with cervical squamous cell carcinoma and endocervical adenocarcinoma. The costimulatory receptor CD226, which competes with CD96, was downregulated in tumors compared with blood and PT tissue. CD96 and T-cell immunoreceptor with Ig and ITIM domains (TIGIT) were upregulated on intratumoral CD8+ T cells. The CD226/CD96/TIGIT signaling ligands were widely expressed in CC tumor tissues. Phenotypical profiling showed that PD-1+CD96+CD8+ TILs exhibited a terminally exhausted effector phenotype with high levels of T-cell immunoglobulin mucin receptor 3 (TIM-3) and granzyme B (GZMB) and extremely low levels of proinflammatory cytokines and cytotoxic molecules. PD-1+CD96 cells exhibited a precursor exhausted phenotype with TCF-1 positivity. CD96 was further upregulated by CD8+ TILs on PD-1 blockade. Treatment with the CD96 blockade significantly enhanced the PD-1 blockade to blunt tumor growth and improve the function of CD8+ TILs in both mouse and CC specimen models.Our findings showed that CD96 and PD-1 cooperatively and negatively regulate the function of CD8+ TILs, and CD96 blockade has promise for use in combination with PD-1 blockade for the treatment of CC.
Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination — PCORnet, United States, January 2021–January 2022
Authors: Jason P. Block, Tegan K. Boehmer, Christopher B. Forrest, Thomas W. Carton, Grace M. Lee, Umed A. Ajani, Dimitri A. Christakis, Lindsay G. Cowell, Christine Draper, Nidhi Ghildayal, Aaron M. Harris, Michael D. Kappelman, Jean Y. Ko, Kenneth H. Mayer, Kshema Nagavedu, Matthew E. Oster, Anuradha Paranjape, Jon Puro, Matthew D. Ritchey, David K. Shay, Deepika Thacker, Adi V. Gundlapalli
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Cardiac complications, particularly myocarditis and pericarditis, have been associated with SARS-CoV-2 (the virus that causes COVID-19) infection (1-3) and mRNA COVID-19 vaccination (2-5). Multisystem inflammatory syndrome (MIS) is a rare but serious complication of SARS-CoV-2 infection with frequent cardiac involvement (6). Using electronic health record (EHR) data from 40 U.S. health care systems during January 1, 2021-January 31, 2022, investigators calculated incidences of cardiac outcomes (myocarditis; myocarditis or pericarditis; and myocarditis, pericarditis, or MIS) among persons aged ≥5 years who had SARS-CoV-2 infection, stratified by sex (male or female) and age group (5-11, 12-17, 18-29, and ≥30 years). Incidences of myocarditis and myocarditis or pericarditis were calculated after first, second, unspecified, or any (first, second, or unspecified) dose of mRNA COVID-19 (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) vaccines, stratified by sex and age group. Risk ratios (RR) were calculated to compare risk for cardiac outcomes after SARS-CoV-2 infection to that after mRNA COVID-19 vaccination. The incidence of cardiac outcomes after mRNA COVID-19 vaccination was highest for males aged 12-17 years after the second vaccine dose; however, within this demographic group, the risk for cardiac outcomes was 1.8-5.6 times as high after SARS-CoV-2 infection than after the second vaccine dose. The risk for cardiac outcomes was likewise significantly higher after SARS-CoV-2 infection than after first, second, or unspecified dose of mRNA COVID-19 vaccination for all other groups by sex and age (RR 2.2-115.2). These findings support continued use of mRNA COVID-19 vaccines among all eligible persons aged ≥5 years.
Secukinumab demonstrates high and sustained efficacy in nail psoriasis: post hoc analysis from phase III trials in patients with psoriatic arthritis
Authors: Kristian Reich, Xenophon Baraliakos, Laura C. Coates, Boni Elewski, Weibin Bao, Torben Kasparek, Corine Gaillez, Effie Pournara, Maher Aassi, Chiara Perella, Alice B. Gottlieb
Journal: British Journal of Dermatology (2022)

Secukinumab showed consistent and sustained efficacy in clearing nail psoriasis in patients with psoriatic arthritis, with or without axial manifestations, irrespective of severity of nail involvement. Reduction of nail disease was also associated with response across all musculoskeletal and skin manifestations of psoriatic arthritis.
PREVALENCE OF PRE-EXISTING ATRIAL FIBRILLATION AND ASSOCIATION WITH IN-HOSPITAL MORTALITY IN PATIENTS WITH COVID-19
Authors: David Sanders, Shengyuan Luo, Jeanne Du-Fay-de-Lavallaz, Joanne Gomez, Tisha Marie Suboc, Henry Darchon Huang, Kim Allan Williams, Annabelle S. Volgman
Journal: Journal of the American College of Cardiology (2022)
Abstract P3-19-19: Intraoperative Radiation Therapy (IORT) : A large integrated healthcare system’s approach and outcomes
Authors: Annie Tang, Jason Kelly, Elizabeth Cureton, Jonathan Svahn, Eva Thomas, Liisa Lyon, Veronica Shim
Journal: Cancer Research (2022)

Abstract Background: With TARGIT-R(Retrospective) showing a higher-than-expected ipsilateral breast tumor recurrence (IBTR) the community setting for intraoperative radiation therapy (IORT), we evaluated IORT outcomes in an integrated health care system.Methods: A retrospective review of early breast cancer patients who received IORT between February 2014-February 2020 was performed. IORT was offered at a single medical center within a large integrated healthcare system. Criteria for IORT included patients ≥50 years with T1, low to intermediate grade, endocrine-responsive HER2- invasive ductal carcinoma. All breast cancer patients were reviewed at weekly multidisciplinary breast conferences, and IORT was offered when patients met the eligibility criteria. Primary outcomes include IBTR, mortality, and complications. Results: Of 5,731 potentially eligible patients, 245 patients (4.3%) underwent IORT. Mean age was 65.4 ± 0.4 years with median follow-up 3.5 years ± 2.2 months. Based on American Society of Radiation Oncology guideline, 51% were suitable, 38.4% cautionary, and 10.6% unsuitable candidates based on the final pathology. The patients were reassigned to the cautionary group because of the margin width and/or extensive DCIS. Unintended boost (primary IORT followed by whole-breast radiation) was given in 6.5% of IORT patients. At median follow-up of 3.5 years, IBRT was 3.7% for all patients. There was one breast-cancer-related mortality (0.4%), and 7 mortality (2.9%) from other causes. Although not statistically significant, there was a trend towards higher recurrence in those not adherent with endocrine treatment than those who were (7.4% vs 1.9%, p=0.07). The overall complication rate was 14.7% with seroma as the most common.Conclusions: At 3.5-year follow-up, our IORT IBTR rate of 3.7%. Our protocol subsequently was modified to require all IORT patients to receive surgical shave margins, WBI for all cautionary patients on the final pathology, and requirement of endocrine treatment. Citation Format: Annie Tang, Jason Kelly, Elizabeth Cureton, Jonathan Svahn, Eva Thomas, Liisa Lyon, Veronica Shim. Intraoperative Radiation Therapy (IORT) : A large integrated healthcare system’s approach and outcomes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-19.
A t(6;14;9)(p22;q22;q34) <scp>three‐way</scp> translocation: Description of a cytogenetically visible variant t(6;9) in acute myeloid leukemia
Authors: Adam C. Smith, Dawn Maze, Daniel Xia, Jose‐Mario Capo‐Chichi, Ian King, Hassan Sibai
Journal: American Journal of Hematology (2022)
Molecular epidemiology of hepatitis A outbreaks and sporadic cases, Latvia, 2017 to 2019
Authors: Oksana Savicka, Reinis Zeltmatis, Jelena Storozenko
Journal: Eurosurveillance (2022)

BackgroundHepatitis A is an acute infection of the liver caused by hepatitis A virus (HAV). Molecular detection and typing of the HAV VP1/P2A genomic region is used for genotyping and outbreak investigations. After a large hepatitis A outbreak in Latvia in 2007-08, only sporadic cases were registered until 2017 when a rise in cases occurred. During 2017-19, 179 laboratory-confirmed hepatitis A cases were notified in Latvia.AimTo investigate the observed increase in hepatitis A cases during 2017 and to determine whether these cases were linked to one another, to risk groups, or to other outbreaks. The majority of HAV samples (69.8%) were typed.MethodsThe VP1/P2A genomic region of HAV was amplified and sequenced for 125 case serum samples. Information about hepatitis-related symptoms, hospitalisation, vaccination, a possible source of infection and suspected countries of origin of the virus were analysed for sequenced cases.ResultsMost HAV strains were subgenotype IA (n = 77), of which 41 were strains circulating among men who have sex with men (MSM) populations in Europe (VRD_521_2016 (n = 32), RIVM-HAV16-090 (n = 7) or V16-25801 (n = 2)). Forty-four cases were subgenotype IB and four cases subgenotype IIIA. However, other clusters and sporadic cases were detected with or without identifying the epidemiological link.ConclusionThis work represents molecular epidemiological data of hepatitis A cases in Latvia from 2017 to 2019. Molecular typing methods allow identification of clusters for public health needs and establishing links with other outbreaks, and to compare Latvian strains with reported strains from other countries.
Risk of SARS-CoV-2 reinfections in children: a prospective national surveillance study between January, 2020, and July, 2021, in England
Authors: Anna A Mensah, Helen Campbell, Julia Stowe, Giulia Seghezzo, Ruth Simmons, Joanne Lacy, Antoaneta Bukasa, Shennae O'Boyle, Mary E Ramsay, Kevin Brown, Shamez N Ladhani
Journal: The Lancet Child & Adolescent Health (2022)

Reinfection after primary SARS-CoV-2 infection is uncommon in adults, but little is known about the risks, characteristics, severity, or outcomes of reinfection in children. We aimed to assess the risk of SARS-CoV-2 reinfection in children and compare this with the risk in adults, by analysis of national testing data for England.In our prospective, national surveillance study to assess reinfection of SARS-CoV-2 in children in England, we used national SARS-CoV-2 testing data to estimate the risk of reinfection at least 90 days after primary infection from Jan 27, 2020, to July, 31, 2021, which encompassed the alpha (B.1.1.7) and delta (B.1.617.2) variant waves in England. Data from children up to age 16 years who met the criteria for reinfection were included. Disease severity was assessed by linking reinfection cases to national hospital admission data, intensive care admission, and death registration datasets.Reinfection rates closely followed community infection rates, with a small peak during the alpha wave and a larger peak during the delta wave. In children aged 16 years and younger, 688 418 primary infections and 2343 reinfections were identified. The overall reinfection rate was 66·88 per 100 000 population, which was higher in adults (72·53 per 100 000) than children (21·53 per 100 000). The reinfection rate after primary infection was 0·68% overall, 0·73% in adults compared with 0·18% in children age younger than 5 years, 0·24% in those aged 5-11 years, and 0·49% in those aged 12-16 years. Of the 109 children admitted to hospital with reinfection, 78 (72%) had comorbidities. Hospital admission rates were similar for the first (64 [2·7%] of 2343) and second episode (57 [2·4%] of 2343) and intensive care admissions were rare (seven children for the first episode and four for reinfections). There were 44 deaths within 28 days after primary infection (0·01%) and none after reinfection.The risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the delta variant wave. Children had a lower risk of reinfection than did adults, but reinfections were not associated with more severe disease or fatal outcomes.UK Health Security Agency.
68Ga-PSMA-11 PET Identified Tumor Recurrence in Prostatectomy Bed With Rising PSA of 0.9 ng/mL but Negative on MRI and 18F-Fluciclovine PET Scan
Authors: Guofan Xu, Yang Lu
Journal: Clinical Nuclear Medicine (2022)

Abstract A 63-year-old man with prostate cancer was treated with prostatectomy who had postoperative PSA of 0.6 ng/mL. A pelvic MRI, whole body bone scan, CT chest and abdomen exams did not show any residual or metastatic prostate disease. His PSA increased to 0.9 ng/mL in two months. A fluciclovine PET did not show any tracer avid metastatic or recurrent disease. A 0.7 cm non-fluciclovine-avid nodule at the left prostatectomy bed was considered benign. A 68 Ga-PSMA-11 PET one month later showed avid radiotracer uptake within this nodule. The patient received androgen deprivation treatment after PSMA PET/CT and responded well.
Endoscopic ultrasound-guided gastroenterostomy versus duodenal stenting for malignant gastric outlet obstruction: an international, multicenter, propensity score-matched comparison
Authors: Roy L. J. van Wanrooij, Giuseppe Vanella, Michiel Bronswijk, Peter de Gooyer, Wim Laleman, Hannah van Malenstein, Francesco Vito Mandarino, Giuseppe Dell’Anna, Paul Fockens, Paolo G. Arcidiacono, Schalk W. van der Merwe, Rogier P. Voermans
Journal: Endoscopy (2022)

Abstract Background Endoscopic duodenal stenting is the current standard treatment for malignant gastric outlet obstruction (GOO) in patients with limited life expectancy. However, duodenal stenting is prone to stent dysfunction. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is a novel technique with potentially superior stent patency. We compared clinical success, safety, and stent dysfunction of EUS-GE and duodenal stenting in patients with malignant GOO using propensity score matching. Methods This international, multicenter, retrospective study analyzed consecutive patients undergoing EUS-GE or duodenal stenting for GOO between 2015 and 2021 in three European centers. Primary outcomes were clinical success (GOO scoring system [GOOSS] ≥ 2) and stent dysfunction (GOOSS ≤ 1 after initial clinical success). A propensity score matching (1:1) analysis was performed using age, sex, underlying disease, disease stage, ascites, and peritoneal carcinomatosis as variables. Results 214 patients underwent EUS-GE (n = 107) or duodenal stenting (n = 107). After propensity score matching, 176 patients were matched and compared. Technical success rates for EUS-GE and duodenal stenting were 94 % (95 %CI 89 %–99 %) vs. 98 % (95 %CI 95 %–100 %), respectively (P = 0.44). Clinical success rates were 91 % (95 %CI 85 %–97 %) vs. 75 % (95 %CI 66 %–84 %; P = 0.008). Stent dysfunction occurred in 1 % (95 %CI 0–4 %) vs. 26 % (95 %CI 15 %–37 %) of patients (P &lt; 0.001). Adverse event rate was 10 % (95 %CI 4 %–17 %) vs. 21 % (95 %CI 12 %–29 %; P = 0.09). Conclusion EUS-GE had higher clinical success and lower stent dysfunction, with similar safety, compared with duodenal stenting, suggesting that EUS-GE may be preferred over duodenal stenting in patients with malignant GOO.
RADIAL ARTERY VASCULAR COMPLICATIONS AND RESOURCE UTILIZATION IN SUBJECTS UNDERGOING AN ANGIOGRAM/PERCUTANEOUS CORONARY INTERVENTION: THE RAVE TRIAL
Authors: M. Fuad Jan, Sara Walczak, Wendy Dunaj, Michelle Bennett, Viviana Zlochiver, Kritika Garg, Ana C. Perez Moreno, Babak Haddadian, Ahmad S. Khraisat, Jayant Khitha, Christopher Koblosky, Tanvir K. Bajwa, Suhail Q. Allaqaband
Journal: Journal of the American College of Cardiology (2022)
Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial
Authors: Min Yan, Quchang Ouyang, Tao Sun, Limin Niu, Jin Yang, Li Li, Yuhua Song, Chunfang Hao, Zhanhong Chen, Armando Orlandi, Naohiro Ishii, Kazuaki Takabe, Gianluca Franceschini, Francesco Ricci, Claire Verschraegen, Zhenzhen Liu, Mengwei Zhang, Huimin Lv, Liping Liu, Xiaohong Yang, Huawu Xiao, Zhichao Gao, Xiaorui Li, Fangyuan Dong, Xiuchun Chen, Jianghua Qiao, Guifang Zhang
Journal: The Lancet Oncology (2022)