tbuckley/cabot-search huggingface dataset:
Abstract 1614: Inducible Nitric Oxide Synthase Upregulates Heme Oxygenase-1 (HO-1) in Myocardium by Enhancing Nrf2 Phosphorylation and Binding to the HO-1 Promoter
Authors: Qianhong Li, Qinghui Ou, Wei Tan, Wen-Jian Wu, Xiaoping Zhu, Lilibeth B Lanceta, Gregg D Rokosh, Yiru Guo, Roberto Bolli
Journal: Circulation (2008)

Previous studies have shown that iNOS gene transfer leads to elevated expression of HO-1, which in turn protects against ischemic injury. However, the mechanism of this effect is unknown. Recently, Nrf2 has emerged as a key transcription factor in response to stress. Thus, we hypothesized that the upregulation of HO-1 by iNOS gene therapy involves an Nrf2-mediated pathway. Mice received injections in anterior LV wall of Av3/LacZ or Av3/iNOS; 3 days later, they were subjected to a 30-min coronary occlusion and 4 h of reperfusion. At 24 h after iNOS gene transfer (confirmed by iNOS immunoblotting), phosphorylated Nrf2 increased significantly in the myocardial nuclear fraction (+ 220% vs. LacZ group, n=6, P&lt;0.05; Fig ); chromatin Nrf2-immunoprecipitation (Nrf2-ChIP) analysis in vivo showed that Nrf2 was specifically recruited to the HO-1 gene promoter (+ 4.7-fold vs. LacZ group, n=4, P&lt;0.05; Fig ). At 3 days after iNOS gene transfer, myocardial HO-1 protein expression increased markedly (+ 2.6-fold vs. LacZ group, n=6, P&lt;0.05; Fig ), but HO-2 did not change (n=3). The infarct-sparing effects of iNOS gene therapy were completely abrogated by disruption of Nrf2 (Nrf2−/−) (62.8±2.1% in Nrf2−/−+Av3/iNOS group, n=5, vs. 15.3±4.3% in WT+Av3/iNOS group, n=7; Fig ). We conclude that iNOS upregulates HO-1 by enhancing Nrf2 phosphorylation and binding to the HO-1 promoter; and targeted disruption of the Nrf2 gene completely abrogates cardioprotection after iNOS gene transfer. These results provide unequivocal molecular genetic evidence for a necessary role of Nrf2 in the protection afforded by iNOS. Thus, activation of Nrf2 is a key molecular event that links iNOS to HO-1.
RARE-61. BODY COMPOSITION AND NUCHAL SKINFOLD THICKNESS IN PEDIATRIC BRAIN TUMOR PATIENTS
Authors: Junxiang Peng, Svenja Boekhoff, Maria Eveslage, Brigitte Bison, Panjarat Sowithayasakul, Hermann L Müller
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Obesity, cardiovascular disease (CVD), and relapse/progression have major impact on prognosis in pediatric brain tumor (BT) patients. Cranial MRI is part of routine follow-up. METHODS In a cross-sectional study, we analyzed nuchal skinfold thickness (NST) on MRI performed for BT follow-up monitoring as a novel parameter for body composition (BC) and CVD in 177 BT patients (40 WHO grade 1–2 BT; 31 grade 3–4 BT; 106 craniopharyngioma (CP)), and 53 healthy controls (HC). Associations of NST with body mass index (BMI), waist-to-height ratio (WHtR), caliper-measured skinfold thickness (cSFT), and blood pressure (BP) were analysed in BT and HC. RESULTS CP patients showed higher BMI, WHtR, NST and cSFT when compared with BT and HC, whereas these differences were not detectable between BT and HC. However, WHO grade 1–2 BT patients were observed with higher BMI, waist circumference and triceps cSFT when compared to WHO grade 3–4 BT patients. NST showed high correlations with BMI, WHtR, and cSFT. NST, BMI and WHtR had predictive value for CVD in terms of increased BP, and in multivariate analysis, only BMI was selected for the final model resulting in an odds ratio of 1.25 (1.14–1.379). In CP patients with hypothalamic involvement/lesion or gross-total resection, rate and degree of obesity were increased. CONCLUSIONS As monitoring of MRI and BC play an important role in follow-up after BT, NST could serve as a novel useful parameter for assessment of BC and CVD risk in BT patients.
Preparations and Appliances
Authors: R R MACINTOSH
Journal: BMJ (1953)

NOVA ET VETERA theatres was approved of, but students should be cautious in their dealings with the other sex lest they fall into the hands of the barbers and suffer from " salivation "-a reference to mercurial treatment.In Roberg's time there were as mafly as fifteen royal grants available for poor medical students, but as there were never as many as fifteen medical students under Roberg at the same time it is pretty safe to conclude that these grants were not over-generous.Even after qualifying as doctors Roberg's pupils encountered many difficulties, including the competition of foreign doctors.Of these Roberg wrote: "The country is flooded by 'agyrtas circumforaneos' to be branded as contraband goods."He was also critical of " perigrinerande medicinae candidater " who returned home primed with knowledge picked up at Halle, Leyden, Oxford, Rheims, and other famous university towns.
Abstract 15965: Efficacy and Safety of Atrial Fibrillation Ablation in Elderly Patients (Age Above 75) in the VA Healthcare System
Authors: Bilal M Alqam, Zaid H Gheith, Fuad J Habash, Khaldia T Khaled, Amjad M Abualsoud, Mohammed Eid Madmani, Srikanth Vallurupalli, Waddah Maskoun
Journal: Circulation (2018)

Introduction: Multi-society consensus statements for Atrial Fibrillation (AF) ablation support similar indications for AF ablation in selected older patients (>75 years old) with AF as in younger p...
Abstract 12147: Predictors and Clinical Significance of Failed Extubation in Neonates After Cardiac Surgery
Authors: Hunter C Wilson, Ray Lowery, Gabe Owens, Stephanie A Goldstein, Megan Gunsaulus, Sunkyung Yu, Mary K Olive
Journal: Circulation (2019)

Introduction: Failed extubation (FE) after pediatric cardiac surgery is associated with significant morbidity. Neonates are at high risk of FE. Further data on risk factors associated with FE and e...
Enhancing the Stability of COVID‐19 Serological Assay through Metal–Organic Framework Encapsulation
Authors: Yixuan Wang, Zheyu Wang, Prashant Gupta, Jeremiah J. Morrissey, Rajesh R. Naik, Srikanth Singamaneni
Journal: Advanced Healthcare Materials (2021)

Abstract Enzyme‐linked immunosorbent assay is widely utilized in serologic assays, including COVID‐19, for the detection and quantification of antibodies against SARS‐CoV‐2. However, due to the limited stability of the diagnostic reagents (e.g., antigens serving as biorecognition elements) and biospecimens, temperature‐controlled storage and handling conditions are critical. This limitation among others makes biodiagnostics in resource‐limited settings, where refrigeration and electricity are inaccessible or unreliable, particularly challenging. In this work, metal–organic framework encapsulation is demonstrated as a simple and effective method to preserve the conformational epitopes of antigens immobilized on microtiter plate under non‐refrigerated storage conditions. It is demonstrated that in situ growth of zeolitic imidazolate framework‐90 (ZIF‐90) renders excellent stability to surface‐bound SARS‐CoV‐2 antigens, thereby maintaining the assay performance under elevated temperature (40 °C) for up to 4 weeks. As a complementary method, the preservation of plasma samples from COVID‐19 patients using ZIF‐90 encapsulation is also demonstrated. The energy‐efficient approach demonstrated here will not only alleviate the financial burden associated with cold‐chain transportation, but also improve the disease surveillance in resource‐limited settings with more reliable clinical data.
PS3-2 Genomic characterization of circulating tumor DNA in advanced genitourinary cancer patients SCRUM-Japan MONSTAR SCREEN
Authors: Norio Nonomura, Taigo Kato, Takao Fujisawa, Masaki Shiota, Masatoshi Eto, Takahiro Osawa, Takashige Abe, Nobuo Shinohara, Ryota Yasumizu, Nobuyuki Tanaka, Mototsugu Oya, Koshiro Nishimoto, Satoshi Horasawa, Naomi Kuramoto, Yoshiaki Nakamura, Hiroya Taniguchi, Takayuki Yoshino, Nobuaki Matsubara
Journal: Annals of Oncology (2021)
Office-Based Methadone Treatment for Opioid Use Disorder and Pharmacy Dispensing: A Scoping Review
Authors: Dennis McCarty, Christina Bougatsos, Brian Chan, Kim A. Hoffman, Kelsey C. Priest, Sara Grusing, Roger Chou
Journal: American Journal of Psychiatry (2021)

The authors conducted a scoping review to survey the evidence landscape for studies that assessed outcomes of treating patients with opioid use disorder with methadone in office-based settings.
Association Between COVID-19 Exposure and Self-reported Compliance With Public Health Guidelines Among Essential Employees at an Institution of Higher Education in the US
Authors: Tracy L. Nelson, Bailey K. Fosdick, Laurie M. Biela, Hayden Schoenberg, Sarah Mast, Emma McGinnis, Michael C. Young, Lori Lynn, Scott Fahrner, Laura Nolt, Tina Dihle, Kendra Quicke, Emily N. Gallichotte, Emily Fitzmeyer, Greg D. Ebel, Kristy Pabilonia, Nicole Ehrhart, Sue VandeWoude
Journal: JAMA Network Open (2021)

Detailed analysis of infection rates paired with behavioral and employee-reported risk factors is vital to understanding how transmission of SARS-CoV-2 infection may be exacerbated or mitigated in the workplace. Institutions of higher education are heterogeneous work units that supported continued in-person employment during the COVID-19 pandemic, providing a test site for occupational health evaluation.To evaluate the association between self-reported protective behaviors and prevalence of SARS-CoV-2 infection among essential in-person employees during the first 6 months of the COVID-19 pandemic in the US.This cross-sectional study was conducted from July 13 to September 2, 2020, at an institution of higher education in Fort Collins, Colorado. Employees 18 years or older without symptoms of COVID-19 who identified as essential in-person workers during the first 6 months of the pandemic were included. Participants completed a survey, and blood and nasal swab samples were collected to assess active SARS-CoV-2 infection via quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and past infection by serologic testing.Self-reported practice of protective behaviors against COVID-19 according to public health guidelines provided to employees.Prevalence of current SARS-CoV-2 infection detected by qRT-PCR or previous SARS-CoV-2 infection detected by an IgG SARS-CoV-2 testing platform. The frequency of protective behavior practices and essential workers' concerns regarding contracting COVID-19 and exposing others were measured based on survey responses.Among 508 participants (305 [60.0%] women, 451 [88.8%] non-Hispanic White individuals; mean [SD] age, 41.1 [12.5] years), there were no qRT-PCR positive test results, and only 2 participants (0.4%) had seroreactive IgG antibodies. Handwashing and mask wearing were reported frequently both at work (480 [94.7%] and 496 [97.8%] participants, respectively) and outside work (465 [91.5%] and 481 [94.7%] participants, respectively). Social distancing was reported less frequently at work (403 [79.5%]) than outside work (465 [91.5%]) (P < .001). Participants were more highly motivated to avoid exposures because of concern about spreading the infection to others (419 [83.0%]) than for personal protection (319 [63.2%]) (P < .001).In this cross-sectional study of essential workers at an institution of higher education, when employees reported compliance with public health practices both at and outside work, they were able to operate safely in their work environment during the COVID-19 pandemic.
Selective blood-brain barrier permeabilization of brain metastases by a type 1 receptor-selective tumor necrosis factor mutein
Authors: Mario F Munoz Pinto, Sandra J Campbell, Christina Simoglou Karali, Vanessa A Johanssen, Claire Bristow, Vinton W T Cheng, Niloufar Zarghami, James R Larkin, Maria Pannell, Arron Hearn, Cherry Chui, Barbara Brinquis Nunez, Evert Bokma, Robert Holgate, Daniel C Anthony, Nicola R Sibson
Journal: Neuro-Oncology (2021)

Metastasis to the brain is a major challenge with poor prognosis. The blood-brain barrier (BBB) is a significant impediment to effective treatment, being intact during the early stages of tumor development and heterogeneously permeable at later stages. Intravenous injection of tumor necrosis factor (TNF) selectively induces BBB permeabilization at sites of brain micrometastasis, in a TNF type 1 receptor (TNFR1)-dependent manner. Here, to enable clinical translation, we have developed a TNFR1-selective agonist variant of human TNF that induces BBB permeabilization, while minimizing potential toxicity.
Cytokine Release from Stimulated PBMC after-HSCT: Results of a Post-Transplant Zinc Oral Supplementation Trial (ZENITH)
Authors: Lorenzo Iovino, Federico Pratesi, Francesco Mazziotta, Enrico Orciuolo, Gabriele Buda, Edoardo Benedetti, Mario Petrini, Paola Migliorini, Sara Galimberti
Journal: Blood (2017)
O5-5 Gemcitabine plus nab-paclitaxel for second-line therapy of pancreatic cancer: A phase II, single-arm, multicenter study
Authors: Gunn Huh, Jin Ho Choi, Sang Hyub Lee, Jung Won Chun, In Rae Cho, Woo Hyun Paik, Ji Kon Ryu, Yong-Tae Kim, Hee Seung Lee, Seungmin Bang
Journal: Annals of Oncology (2021)
Integrated Physical Activity Campaign With Wearable Devices and Practitioner Consultation
Authors: Paul Ritvo, Megan Kirk, Meysam Pirbaglou
Journal: JAMA Network Open (2021)

Alexander Hodkinson, PhD; Evangelos Kontopantelis, PhD; Charles Adeniji, MD; Harm van Marwijk, PhD; Brian McMillian, PhD; Peter Bower, PhD; Maria Panagioti, PhD
Liver and/or kidney transplantation after SARS-CoV-2 infection: Prevalence, short-term outcome and kinetics of serum IgG antibodies
Authors: J. Verbeek, C. Vrij, P. Vermeersch, S. Vets, K. Lagrou, I. Jochmans, D. Monbaliu, J. Pirenne, D. Kuypers, F. Nevens
Journal: Journal of Hepatology (2021)
Serotype transmission dynamics and reduced incidence of invasive pneumococcal disease caused by different serotypes after implementation of non-pharmaceutical interventions during COVID-19 pandemic
Authors: Rajendra Prasad Janapatla, Chyi-Liang Chen, Anna Dudek, Hsin-Chieh Li, Hsin-Ping Yang, Lin-Hui Su, Cheng-Hsun Chiu
Journal: European Respiratory Journal (2021)

<b>Significant reduction in the incidence rates of both vaccine and non-vaccine serotype invasive pneumococcal disease among children and adults during the COVID-19 pandemic were observed after the implementation of non-pharmaceutical interventions</b>https://bit.ly/36CAute
Second-Generation Bruton's Tyrosine Kinase Inhibitors: Simply the Best Treatments for Chronic Lymphocytic Leukemia?
Authors: Deborah M. Stephens
Journal: Journal of Clinical Oncology (2021)

Ibrutinib is the oral, covalently binding inhibitor of Bruton's tyrosine kinase (BTK) that revolutionized therapy for patients with chronic lymphocytic leukemia (CLL).2][3] For a period, ibrutinib was considered optimal therapy for many patients with CLL.As ibrutinib is intended to be taken continuously for an indefinite period, tolerability of the drug is quite important.With longer follow-up, notable toxicities were documented for patients with CLL, including atrial fibrillation (11%-16%) and hypertension (20%-26%). 1,2Toxicities were cited as the cause of ibrutinib discontinuation in up to 28% of patients in phase III studies. 1 With the goals of maintaining the efficacy seen with ibrutinib but reducing toxicity through more selective BTK inhibition, second-generation BTK inhibitors were developed.Acalabrutinib is an oral covalently binding BTK inhibitor that is approved by the US Food and Drug Administration (FDA) for marketing in the treatment of CLL.This approval was based on acalabrutinib's ability to prolong progression-free survival (PFS) when compared with standard chemoimmunotherapy regimens in phase III studies. 4,5Acalabrutinib discontinuations because of toxicity were only seen in up to 11% of patients in these studies. 4,5It was hypothesized that acalabrutinib would have similar efficacy and less toxicity to ibrutinib.Therefore, a direct head-to-head comparison was undertaken.In the article accompanying this editorial, ELEVATE RR study is a phase III, randomized, open-label, noninferiority study with a primary end point of independent review committee-assessed noninferiority of PFS between acalabrutinib and ibrutinib. 6The study enrolled 533 patients with previously treated CLL and prognostic factors of del(17p) (45%) and/or del(11q) (64%), which were both considered high-risk factors at the time of study design [Del(11q) has since been associated with favorable prognosis in the setting of ibrutinib therapy. 7] After a median follow-up 41 months, acalabrutinib was found to be noninferior to ibrutinib with median PFS of 38.4 months in both arms (hazard ratio, 1.00).As anticipated, toxicities were experienced less by patients receiving acalabrutinib, including diarrhea, arthralgia, bruising, muscle spasm, and dyspepsia.Especially notable, atrial fibrillation and hypertension occurred less frequently with acalabrutinib.
A dark side to NS1 antibodies?
Authors: Davide F. Robbiani, Daniel Růžek
Journal: The Journal of Experimental Medicine (2021)

The NS1 protein of flaviviruses is taking center stage. Recent work has made it an attractive target for development of vaccines and immunotherapeutics. Cavazzoni and colleagues (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210580) now reveal a dark side to NS1, linking it to the development of self-reactive antibodies.
Publisher Correction: Publisher Correction: The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics
Authors: Seppo Salminen, Maria Carmen Collado, Akihito Endo, Colin Hill, Sarah Lebeer, Eamonn M. M. Quigley, Mary Ellen Sanders, Raanan Shamir, Jonathan R. Swann, Hania Szajewska, Gabriel Vinderola
Journal: Nature Reviews Gastroenterology & Hepatology (2021)
Abstract 11432: The Influence of Race/Ethnicity on Burden of Atrial Fibrillation: The KP RHYTHM Study
Authors: Jingrong Yang, Kristi Reynolds, Nigel Gupta, Judith C Lenane, Elisha Garcia, Sue Hee Sung, Teresa N Harrison, Matthew Solomon, Alan S Go
Journal: Circulation (2019)

Introduction: Conflicting studies exist about whether the risk of developing atrial fibrillation (AF) varies by race, with even less known about whether race/ethnicity is associated with differenti...
P44-3 Thrombotic microangiopathy (TMA) after treatment with nivolumab in advanced gastric cancer
Authors: Tomoyuki Sakamoto, Yoshiaki Mihara, Yosuke Horita, Tsuyoshi Fukumoto, Takashi Ichimura, Yusuke Watanabe, Shuji Takahira, Manabu Nemoto, Shigehisa Mori, Yuichi Nakamura, Tetsuya Hamaguchi
Journal: Annals of Oncology (2021)
Delayed respiratory syncytial virus epidemic in children after relaxation of COVID-19 physical distancing measures, Ashdod, Israel, 2021
Authors: Moran Weinberger Opek, Yonatan Yeshayahu, Aharona Glatman-Freedman, Zalman Kaufman, Nadav Sorek, Tal Brosh-Nissimov
Journal: Eurosurveillance (2021)

Following low incidence of respiratory syncytial virus (RSV) infections in 2020 during the COVID-19 pandemic, we noted a resurgence in hospitalised children in spring/summer 2021 following relaxation of public health measures. We compared this outbreak to previous autumn/winter seasons. We found higher weekly case numbers and incidence rates, more cases from urban neighbourhoods with lower socioeconomic status, and similar clinical presentation and severity. Public health implications include the re-evaluation of palivizumab administration and the need for surge capacity planning.
M6A Demethylase ALKBH5 Regulates PD-L1 Expression and Tumor Immunoenvironment in Intrahepatic Cholangiocarcinoma
Authors: Xinyao Qiu, Shuai Yang, Shan Wang, Jianmin Wu, Bo Zheng, Kaiting Wang, Siyun Shen, Seogsong Jeong, Zhixuan Li, Yanjing Zhu, Tong Wu, Xuan Wu, Rui Wu, Weiwei Liu, Hong-Yang Wang, Lei Chen
Journal: Cancer Research (2021)

N6-methyladenosine (m6A) has been reported as an important mechanism of posttranscriptional regulation. Programmed death-ligand 1 (PD-L1) is a primary immune inhibitory molecule expressed on tumor cells that promotes immune evasion. Here we report ALKBH5 as an important m6A demethylase that orchestrates PD-L1 expression in intrahepatic cholangiocarcinoma (ICC). Regulation of PD-L1 expression by ALKBH5 was confirmed in human ICC cell lines. Sequencing of the m6A methylome identified PD-L1 mRNA as a direct target of m6A modification whose levels were regulated by ALKBH5. Furthermore, ALKBH5 and PD-L1 mRNA were shown to interact. ALKBH5 deficiency enriched m6A modification in the 3'UTR region of PD-L1 mRNA, thereby promoting its degradation in a YTHDF2-dependent manner. In vitro and in vivo, tumor-intrinsic ALKBH5 inhibited the expansion and cytotoxicity of T cells by sustaining tumor cell PD-L1 expression. The ALKBH5-PD-L1-regulating axis was further confirmed in human ICC specimens. Single-cell mass cytometry analysis unveiled a complex role of ALKBH5 in the tumor immune microenvironment by promoting the expression of PD-L1 on monocytes/macrophages and decreasing the infiltration of myeloid-derived suppressor-like cells. Analysis of specimens from patients receiving anti-PD1 immunotherapy suggested that tumors with strong nuclear expression patterns of ALKBH5 are more sensitive to anti-PD1 immunotherapy. Collectively, these results describe a new regulatory mechanism of PD-L1 by mRNA epigenetic modification by ALKBH5 and the potential role of ALKBH5 in immunotherapy response, which might provide insights for cancer immunotherapies. SIGNIFICANCE: This study identifies PD-L1 mRNA as a target of ALKBH5 and reveals a role for ALKBH5 in regulating the tumor immune microenvironment and immunotherapy efficacy.
Lomerizine 2HCl inhibits cell proliferation and induces protective autophagy in colorectal cancer via the PI3K/Akt/mTOR signaling pathway
Authors: Xiang‐Peng Tan, Yan He, Yun‐Na Huang, Can‐Can Zheng, Jun‐Qi Li, Qin‐Wen Liu, Ming‐Liang He, Bin Li, Wen‐Wen Xu
Journal: MedComm (2021)

Colorectal cancer (CRC) is one of the most common malignancies currently. Despite advances in drug development, the survival and response rates in CRC patients are still poor. In our previous study, a library comprised of 1056 bioactive compounds was used for screening of drugs that could suppress CRC. Lomerizine 2HCl, which is an approved prophylactic drug for migraines, was selected for our studies. The results of in vitro and in vivo assays suggested that lomerizine 2HCl suppresses cell growth and promotes apoptosis in CRC cells. Moreover, lomerizine 2HCl inhibits cell migration and invasion of CRC. RNA sequencing analysis and Western blotting confirmed that lomerizine 2HCl can inhibit cell growth, migration, and invasion through PI3K/AKT/mTOR signaling pathway and induces protective autophagy in CRC. Meanwhile, autophagy inhibition by 3-methyladenine (3-MA) increases lomerizine 2HCl-induced cell apoptosis. Taken together, these results imply that lomerizine 2HCl is a potential anticancer agent, and the combination of lomerizine 2HCl and autophagy inhibitors may serve as a novel strategy to increase the antitumor efficacy of agents in the treatment of CRC.