tbuckley/cabot-search huggingface dataset:
Construction of an anti-hepatitis B virus preS1 antibody and usefulness of preS1 measurement for chronic hepatitis B patients
Authors: Haruna Hatooka, Yumi Shimomura, Michio Imamura, Yuji Teraoka, Kei Morio, Hatsue Fujino, Atsushi Ono, Takashi Nakahara, Eisuke Murakami, Masami Yamauchi, Tomokazu Kawaoka, Grace Naswa Makokha, Daiki Miki, Masataka Tsuge, Akira Hiramatsu, Hiromi Abe-Chayama, C. Nelson Hayes, Hiroshi Aikata, Shinji Tanaka, Kazuaki Chayama
Journal: Journal of Infection (2021)
Adverse Pregnancy Outcomes and Incident Heart Failure in the Women’s Health Initiative
Authors: Aleksander L. Hansen, Marc Meller Søndergaard, Mark A. Hlatky, Eric Vittinghof, Gregory Nah, Marcia L. Stefanick, JoAnn E. Manson, Leslie V. Farland, Gretchen L. Wells, Morgana Mongraw-Chaffin, Erica P. Gunderson, Linda Van Horn, Robert A. Wild, Buyun Liu, Aladdin H. Shadyab, Matthew A. Allison, Simin Liu, Charles B. Eaton, Michael C. Honigberg, Nisha I. Parikh
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Some prior evidence suggests that adverse pregnancy outcomes (APOs) may be associated with heart failure (HF). Identifying unique factors associated with the risk of HF and studying HF subtypes are important next steps. <h3>Objective</h3> To investigate the association of APOs with incident HF overall and stratified by HF subtype (preserved vs reduced ejection fraction) among postmenopausal women in the Women's Health Initiative (WHI). <h3>Design, Setting, and Participants</h3> In 2017, an APO history survey was administered in the WHI study, a large multiethnic cohort of postmenopausal women. The associations of 5 APOs (gestational diabetes, hypertensive disorders of pregnancy [HDP], low birth weight, high birth weight, and preterm delivery) with incident adjudicated HF were analyzed. In this cohort study, the association of each APO with HF was assessed using logistic regression models and with HF subtypes using multinomial regression, adjusting for age, sociodemographic characteristics, smoking, randomization status, reproductive history, and other APOs. Data analysis was performed from January 2020 to September 2021. <h3>Exposures</h3> APOs (gestational diabetes, HDP, low birth weight, high birth weight, and preterm delivery). <h3>Main Outcomes and Measures</h3> All confirmed cases of women hospitalized with HF and HF subtype were adjudicated by trained physicians using standardized methods. <h3>Results</h3> Of 10 292 women (median [IQR] age, 60 [55-64] years), 3185 (31.0%) reported 1 or more APO and 336 (3.3%) had a diagnosis of HF. Women with a history of any APO had a higher prevalence of hypertension, diabetes, coronary heart disease, or smoking. Of the APOs studied, only HDP was significantly associated with HF with a fully adjusted odds ratio (OR) of 1.75 (95% CI, 1.22-2.50), and with HF with preserved ejection fraction in fully adjusted models (OR, 2.06; 95% CI, 1.29-3.27). In mediation analyses, hypertension explained 24% (95% CI, 12%-73%), coronary heart disease 23% (95% CI, 11%-68%), and body mass index 20% (95% CI, 10%-64%) of the association between HDP and HF. <h3>Conclusions and Relevance</h3> In this large cohort of postmenopausal women, HDP was independently associated with incident HF, particularly HF with preserved ejection fraction, and this association was mediated by subsequent hypertension, coronary heart disease, and obesity. These findings suggest that monitoring and modifying these factors early in women presenting with HDP may be associated with reduced long-term risk of HF.
The fecal mycobiome in non-alcoholic fatty liver disease
Authors: Münevver Demir, Sonja Lang, Phillipp Hartmann, Yi Duan, Anna Martin, Yukiko Miyamoto, Marina Bondareva, Xinlian Zhang, Yanhan Wang, Philipp Kasper, Corinna Bang, Christoph Roderburg, Frank Tacke, Hans-Michael Steffen, Tobias Goeser, Andrey Kruglov, Lars Eckmann, Peter Stärkel, Derrick E. Fouts, Bernd Schnabl
Journal: Journal of Hepatology (2021)
Five-Year Cumulative Incidence and Progression of Myopic Maculopathy in a German Population
Authors: Susanne Hopf, Franziska Heidt, Christina A. Korb, Andreas Schulz, Thomas Münzel, Philipp S. Wild, Manfred Beutel, Irene Schmidtmann, Karl J. Lackner, Norbert Pfeiffer, Alexander K. Schuster
Journal: Ophthalmology (2021)
Targeted Proteomics of Pulmonary Hypertension in Sickle Cell Disease
Authors: Varshini Babu, Jane A. Little, Claudia R. Morris, Roberto Machado, J Simon R Gibbs, Gregory J. Kato, Victor R. Gordeuk, Mark T. Gladwin, Yingze Zhang, Seyed Mehdi Nouraie
Journal: Blood (2021)
An <i>In Vivo</i> CRISPR Screen Identifies Stepwise Genetic Dependencies of Metastatic Progression
Authors: Manuel C. Scheidmann, Francesc Castro-Giner, Karin Strittmatter, Ilona Krol, Aino Paasinen-Sohns, Ramona Scherrer, Cinzia Donato, Sofia Gkountela, Barbara M. Szczerba, Zoi Diamantopoulou, Simone Muenst, Tatjana Vlajnic, Leo Kunz, Marcus Vetter, Christoph Rochlitz, Verdon Taylor, Claudio Giachino, Timm Schroeder, Randall J. Platt, Nicola Aceto
Journal: Cancer Research (2021)

Abstract Blood-borne metastasis of breast cancer involves a series of tightly regulated sequential steps, including the growth of a primary tumor lesion, intravasation of circulating tumor cells (CTC), and adaptation in various distant metastatic sites. The genes orchestrating each of these steps are poorly understood in physiologically relevant contexts, owing to the rarity of experimental models that faithfully recapitulate the biology, growth kinetics, and tropism of human breast cancer. Here, we conducted an in vivo loss-of-function CRISPR screen in newly derived CTC xenografts, unique in their ability to spontaneously mirror the human disease, and identified specific genetic dependencies for each step of the metastatic process. Validation experiments revealed sensitivities to inhibitors that are already available, such as PLK1 inhibitors, to prevent CTC intravasation. Together, these findings present a new tool to reclassify driver genes involved in the spread of human cancer, providing insights into the biology of metastasis and paving the way to test targeted treatment approaches. Significance: A loss-of-function CRISPR screen in human CTC-derived xenografts identifies genes critical for individual steps of the metastatic cascade, suggesting novel drivers and treatment opportunities for metastatic breast cancers.
Sedation and Ventilator Liberation Protocol vs Usual Care and Duration of Invasive Ventilation in Pediatric Intensive Care Units
Authors: Nobuyuki Nosaka, Takahiro Masuda
Journal: JAMA (2021)

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Statins do not commonly cause muscle pain and stiffness
Authors: Helen Saul, Deniz Gursul, Samantha Cassidy, Liam Smeeth, Alexander Perkins
Journal: BMJ (2021)

The studyHerrett E, Williamson E, Brack K, et al. The effect of statins on muscle symptoms in primary care: the StatinWISE series of 200 N-of-1 RCTs. Health Technol Assess 2021;25:16.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/statins-not-likely-to-cause-muscle-pain-stiffness/.
Gestational Weight Gain in Women With Obesity and Consideration of Infant Morbidity and Mortality in Clinical Practice
Authors: Shiao-Yng Chan
Journal: JAMA Network Open (2021)

Lijun Wang, PhD; Xiaoyu Zhang, MPH; Tingting Chen, MPH; Jun Tao, BMed; Yanduo Gao, MPH; Li Cai, PhD; Huijun Chen, MD; Chuanhua Yu, PhD
Human NLRP1: From the shadows to center stage
Authors: Stefan Bauernfried, Veit Hornung
Journal: The Journal of Experimental Medicine (2021)

In response to infection or cell damage, inflammasomes form intracellular multimeric protein complexes that play an essential role in host defense. Activation results in the maturation and subsequent secretion of pro-inflammatory cytokines of the IL-1 family and a specific cell death coined pyroptosis. Human NLRP1 was the first inflammasome-forming sensor identified at the beginning of the millennium. However, its functional relevance and its mechanism of activation have remained obscure for many years. Recent discoveries in the NLRP1 field have propelled our understanding of the functional relevance and molecular mode of action of this unique inflammasome sensor, which we will discuss in this perspective.
191P Fecal microbiome in soft-tissue sarcoma (STS) patients treated with neoadjuvant immune checkpoint blockade (ICB)
Authors: R. Traweek, E. Keung, N.J. Ajami, S. Duncan, E. Burton, T. Tate, K. Callahan, D. Ingram, K. Wani, A.J. Lazar, W-L. Wang, B.A. Guadagnolo, A.J. Bishop, J.A. Wargo, N. Somaiah, C.L. Roland, E.F. Nassif
Journal: Annals of Oncology (2021)
Contemporary Etiologies, Outcomes, and Novel Risk Score for Isolated Tricuspid Regurgitation
Authors: Tom Kai Ming Wang, Kevser Akyuz, Amgad Mentias, Jason Kirincich, Alejandro Duran Crane, Samantha Xu, Zoran B. Popovic, Bo Xu, A. Marc Gillinov, Gosta B. Pettersson, Brian P. Griffin, Milind Y. Desai
Journal: JACC. Cardiovascular imaging (2021)
Sodium–glucose co‐transporter 2 inhibitors as an early, first‐line therapy in patients with heart failure and reduced ejection fraction
Authors: Daniela Tomasoni, Gregg C. Fonarow, Marianna Adamo, Stefan D. Anker, Javed Butler, Andrew J.S. Coats, Gerasimos Filippatos, Stephen J. Greene, Theresa A. McDonagh, Piotr Ponikowski, Giuseppe Rosano, Petar Seferovic, Muthiah Vaduganathan, Adriaan A. Voors, Marco Metra
Journal: European Journal of Heart Failure (2021)
Impact of the COVID-19 Pandemic on Treatment Patterns for Patients With Metastatic Solid Cancer in the United States
Authors: Ravi B Parikh, Samuel U Takvorian, Daniel Vader, E Paul Wileyto, Amy S Clark, Daniel J Lee, Gaurav Goyal, Gabrielle B Rocque, Efrat Dotan, Daniel M Geynisman, Pooja Phull, Philippe E Spiess, Roger Y Kim, Amy J Davidoff, Cary P Gross, Natalia Neparidze, Rebecca A Miksad, Gregory S Calip, Caleb M Hearn, Will Ferrell, Lawrence N Shulman, Ronac Mamtani, Rebecca A Hubbard
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background The COVID-19 pandemic has led to delays in patients seeking care for life-threatening conditions; however, its impact on treatment patterns for patients with metastatic cancer is unknown. We assessed the COVID-19 pandemic’s impact on time to treatment initiation (TTI) and treatment selection for patients newly diagnosed with metastatic solid cancer. Methods We used an electronic health record–derived longitudinal database curated via technology-enabled abstraction to identify 14 136 US patients newly diagnosed with de novo or recurrent metastatic solid cancer between January 1 and July 31 in 2019 or 2020. Patients received care at approximately 280 predominantly community-based oncology practices. Controlled interrupted time series analyses assessed the impact of the COVID-19 pandemic period (April-July 2020) on TTI, defined as the number of days from metastatic diagnosis to receipt of first-line systemic therapy, and use of myelosuppressive therapy. Results The adjusted probability of treatment within 30 days of diagnosis was similar across periods (January-March 2019 = 41.7%, 95% confidence interval [CI] = 32.2% to 51.1%; April-July 2019 = 42.6%, 95% CI = 32.4% to 52.7%; January-March 2020 = 44.5%, 95% CI = 30.4% to 58.6%; April-July 2020 = 46.8%, 95% CI= 34.6% to 59.0%; adjusted percentage-point difference-in-differences = 1.4%, 95% CI = −2.7% to 5.5%). Among 5962 patients who received first-line systemic therapy, there was no association between the pandemic period and use of myelosuppressive therapy (adjusted percentage-point difference-in-differences = 1.6%, 95% CI = −2.6% to 5.8%). There was no meaningful effect modification by cancer type, race, or age. Conclusions Despite known pandemic-related delays in surveillance and diagnosis, the COVID-19 pandemic did not affect TTI or treatment selection for patients with metastatic solid cancers.
Incidence and trends of basal cell carcinoma in Sweden: a population‐based registry study*
Authors: Johan Kappelin, Adele C. Green, Åsa Ingvar, Ingela Ahnlide, Kari Nielsen
Journal: British Journal of Dermatology (2021)

Basal cell carcinoma (BCC) is the most common skin cancer. Incidence is largely unknown because of incomplete, or lack of, registration in most countries.To assess current incidence rates and recent trends for BCC in the Swedish population.Patient- and tumour-related features of all histologically confirmed BCC tumours diagnosed in Sweden from 2004 to 2017 were extracted from the population-based Swedish BCC Registry. Incidence rates were standardized to the 2013 European Standard Population and trends were analysed using Poisson regression models.The age-standardized person-based incidence rate of BCC in Sweden was 405 per 100 000 in 2017, rising from 308 per 100 000 in 2004, corresponding to an annual relative increase of 1·8% (women, 2·1%; men, 1·4%). Incidence was highest in elderly people and the most common tumour site was the head and neck. In 2017, the most common BCC subtypes were nodular and micronodular/infiltrative BCC (each 31%). Incidence of aggressive BCC subtypes increased faster than other subtypes.BCC incidence rates in Sweden are relatively high and increasing. The increasing trends were more pronounced in women and for aggressive BCC subtypes. What is already known about this topic? Basal cell carcinoma (BCC) is the most common skin cancer in white populations and its incidence is increasing. BCC is seldom registered in national population-based cancer registries, therefore incidence estimates are extrapolated from small studies or incomplete registers. BCC occurs more often in men than in women and occurs most commonly on the head and neck, followed by the trunk. What does this study add? This study provides current BCC incidence rates for an entire European population. Sex-specific trends show that BCC incidence is increasing faster in women in Sweden. Aggressive BCC subtypes appear to be increasing faster than other subtypes.
WT1 and DNMT3A Play an Essential Function and Represent Therapeutic Vulnerabilities in Certain AML Samples, As Shown By CRISPR/Cas9 Mediated Knockout in PDX Models In Vivo
Authors: Maryam Ghalandary, Yuqiao Gao, Martin Becker, Diana Amend, Klaus H. Metzeler, Maja Rothenberg-Thurley, Irmela Jeremias
Journal: Blood (2021)
T-cells of invasive candidiasis patients show patterns of T-cell-exhaustion suggesting checkpoint blockade as treatment option
Authors: Sibylle C. Mellinghoff, Martin Thelen, Christiane Bruns, Maria Garcia-Marquez, Pia Hartmann, Tatjana Lammertz, Jonas Lehmann, Angela Nowag, Jannik Stemler, Kerstin Wennhold, Oliver A. Cornely, Michael S. von Bergwelt-Baildon, Hans A. Schlößer
Journal: Journal of Infection (2021)
Contribution of Interleukin‐4–Induced Epithelial Cell Senescence to Glandular Fibrosis in <scp>IgG4‐Related</scp> Sialadenitis
Authors: Sai‐Nan Min, Meng‐Qi Zhu, Xiang‐Di Mao, Wei Li, Tai Wei, Mei Mei, Yan Zhang, Li‐Ling Wu, Guang‐Yan Yu, Xin Cong
Journal: Arthritis & Rheumatology (2021)

IgG4-related sialadenitis (IgG4-RS) is a chronic fibroinflammatory disease characterized by glandular fibrosis and hyposalivation. This study was undertaken to explore the role of cellular senescence in the pathogenesis of IgG4-RS-related fibrosis.The expression of senescence markers and proinflammatory cytokines in the submandibular glands (SMGs) of IgG4-RS patients (n = 18) and controls (n = 14) was determined by proteomics, real-time polymerase chain reaction, Western blotting, and immunohistochemistry. After interleukin-4 (IL-4) treatment, high-throughput RNA sequencing was performed to identify the differentially expressed genes in SMG-C6 cells. A glandular fibrosis model was established by the intraglandular injection of IL-4 into mouse SMGs (n = 8 per group).Salivary acinar and ductal epithelial cells underwent senescence in IgG4-RS patients, as indicated by the elevated activity of senescence-associated β-galactosidase, lipofuscin accumulation, enhanced expression of senescence markers (p53 and p16INK4A ), and up-regulation of senescence-associated secretory phenotype factors. Moreover, there was a significant increase in IL-4 levels in SMGs from IgG4-RS patients (P < 0.01), which positively correlated with p16INK4A expression and the fibrosis score. Incubation with IL-4 exacerbated salivary epithelial cell senescence by increasing the expression of p16INK4A through the reactive oxygen species (ROS)/p38 MAPK pathway. Supernatant collected from IL-4-induced senescent SMG-C6 cells enhanced fibroblast activation and matrix protein production (P < 0.05). Furthermore, injecting mice with IL-4 promoted fibrosis and senescence phenotypes in SMGs in vivo.The cellular senescence induced by IL-4 through the ROS/p38 MAPK-p16INK4A pathway promotes fibrogenesis in IgG4-RS. Our data suggest that cellular senescence could serve as a novel therapeutic target for treating IgG4-RS.
Alteplase and Thrombectomy — Not a Bridge to Dismantle
Authors: Alfonso Ciccone
Journal: New England Journal of Medicine (2021)

In the past few years, thrombectomy — the removal of a thrombus under angiographic guidance — has become an accepted treatment for acute ischemic stroke caused by occlusion of a large cerebral vessel.1 Guidelines have included the use of intravenous alteplase preceding thrombectomy1 if there are no contraindications to its use, and most randomized, controlled trials of thrombectomy have used alteplase in this manner. After the efficacy of thrombectomy was established, the obvious question of whether it could be effective without preceding intravenous thrombolysis arose. In the somewhat parallel case of acute myocardial infarction, percutaneous coronary intervention (PCI) alone has . . .
Abstract 17116: Recurrent Atrial Myxomas As A Presenting Feature Of Carney Complex
Authors: Mustafa Alam, Tavleen Singh, Anandbir Bath, Shadwan Alsafwah
Journal: Circulation (2021)

Case Presentation: A 24-year-old man with a history of adrenal insufficiency on hydrocortisone presented to the hospital after losing consciousness in a swimming pool and was found to have an acute MCA stroke. PMHx was significant for left atrial myxoma status post resection 3 years ago, known L frontal brain, L adrenal, and testicular masses status post-resection. His father had a history of resected left atrial mass. Cardiology was consulted for a L atrial mass on the bedside echocardiogram upon initial emergency evaluation, during which the patient was placed on mechanical ventilation with stable vitals. The cardiovascular exam revealed a midsternal scar but was otherwise normal. Pulses were 2+ bilaterally on the upper and lower extremities. The skin was noted to have multiple hyperpigmented macules resembling cafe-au lait spots. The patient underwent mechanical thrombectomy with thrombolysis for his large MCA occlusion. His postoperative course was complicated by a worsening neuro exam in the setting of mid-line shift for which he had undergone decompressive hemicraniectomy. His adrenal insufficiency was managed by endocrinology. A TTE was significant for a L atrial mass measuring 4.8 cm attached to the interatrial septum with a stalk. A CT scan identified 2 discrete hypodensities of 8 mm and 3.8 cm which were thought to be the cardioembolic source for the stroke. An abdominal CT revealed a recurrent L adrenal neoplasm with absent R adrenal gland post resection of neoplasm. Conservative cardiac management was elected in the setting of a worsening neuroprognosis with follow-up post neurologic insult. Discussion: Considering the constellation of neoplastic and cutaneous findings, this was diagnosed as a case of Carney complex. This case identifies recurrent myxoma as a unique feature of Carney complex, ruling out other differentials such as neurofibromatosis and MEN syndrome. It highlights the importance of screening to prevent embolic stroke from recurrent myxomas.
New Therapeutic Horizons in Chronic Kidney Disease: The Role of SGLT2 Inhibitors in Clinical Practice
Authors: Marc Evans, Angharad R. Morgan, Martin B. Whyte, Wasim Hanif, Stephen C. Bain, Philip A. Kalra, Sarah Davies, Umesh Dashora, Zaheer Yousef, Dipesh C. Patel, W. David Strain
Journal: Drugs (2021)
CstF64-Induced Shortening of the <i>BID</i> 3′UTR Promotes Esophageal Squamous Cell Carcinoma Progression by Disrupting ceRNA Cross-talk with <i>ZFP36L2</i>
Authors: Ai Lin, Ping Ji, Xiangjie Niu, Xuan Zhao, Yamei Chen, Weiling Liu, Yachen Liu, Wenyi Fan, Yanxia Sun, Chuanwang Miao, Shaosen Zhang, Wen Tan, Dongxin Lin, Eric J. Wagner, Chen Wu
Journal: Cancer Research (2021)

Abstract The majority of human genes have multiple polyadenylation sites, which are differentially used through the process of alternative polyadenylation (APA). Dysregulation of APA contributes to numerous diseases, including cancer. However, specific genes subject to APA that impact oncogenesis have not been well characterized, and many cancer APA landscapes remain underexplored. Here, we used dynamic analyses of APA from RNA-seq (DaPars) to define both the 3′UTR APA profile in esophageal squamous cell carcinoma (ESCC) and to identify 3′UTR shortening events that may drive tumor progression. In four distinct squamous cell carcinoma datasets, BID 3′UTRs were recurrently shortened and BID mRNA levels were significantly upregulated. Moreover, system correlation analysis revealed that CstF64 is a candidate upstream regulator of BID 3′UTR length. Mechanistically, a shortened BID 3′UTR promoted proliferation of ESCC cells by disrupting competing endogenous RNA (ceRNA) cross-talk, resulting in downregulation of the tumor suppressor gene ZFP36L2. These in vitro and in vivo results were supported by human patient data whereby 3′UTR shortening of BID and low expression of ZFP36L2 are prognostic factors of survival in ESCC. Collectively, these findings demonstrate that a key ceRNA network is disrupted through APA and promotes ESCC tumor progression. Significance: High-throughput analysis of alternative polyadenylation in esophageal squamous cell carcinoma identifies recurrent shortening of the BID 3′UTR as a driver of disease progression.
Table of contents
Journal: Hepatology (2021)

Cover Figure: Im et al.' s systematic review of 3,920 unique rodent models of non-alcoholic fatty liver disease (NAFLD) identified the suitability of NAFLD models for studying different aspects of disease while also highlighting the challenge of reproducibility in the field.Overall, they found that rodents fed a high fat, high fructose diet most closely recapitulate human NAFLD both histologically and metabolically.