tbuckley/cabot-search huggingface dataset:
Abstract 15757: Association of Ischemic Mitral Regurgitation Proportionality With Outcomes After Mitral Valve Surgery: A Cardiothoracic Surgical Trials Network Analysis
Authors: Gennaro Giustino, Jessica Overbey, Patrick T O’Gara, Annetine C Gelijns, Lynne W Stevenson, Alan J Moskowitz, Pierre Voisine, Michael J Mack, Michael A Acker, A. Marc Gillinov, Donna M Mancini, Emilia Bagiella, Anuradha Lala, Y. Joseph Woo, Judy Hung, Paul A Grayburn
Journal: Circulation (2019)

Introduction: The severity of secondary mitral regurgitation (MR) relative to left ventricular (LV) volume might predict the clinical response to treatments directed to either the mitral valve (MV)...
Six-Month Efficacy and Toxicity Profile of BNT162b2 Vaccine in Cancer Patients with Solid Tumors
Authors: Ithai Waldhorn, Roy Holland, Tal Goshen-Lago, Yelena Shirman, Moran Szwarcwort-Cohen, Anat Reiner-Benaim, Yael Shachor-Meyouhas, Khetam Hussein, Liana Fahoum, Avivit Peer, Ronit Almog, Yuval Shaked, Michael Halberthal, Irit Ben-Aharon
Journal: Cancer Discovery (2021)

Abstract We had previously reported short-term efficacy, immunogenicity, and safety of the BNT162b2 vaccine among cancer patients with solid tumors. We aimed to evaluate these outcomes at six months postvaccination. The study cohort comprised patients who were on treatment during vaccination and throughout six months postvaccination. Serologic tests were performed after second vaccination and six months afterward. An age-matched cohort of health care workers served as controls. Documentation of COVID-19 infection, blood tests, and imaging studies during the study period was reviewed. Participants included 154 patients and 135 controls. Six months postvaccination, 122 (79%) patients were seropositive compared with 114 (84%) controls (P = 0.32). Serology titer dramatically decreased in a similar manner in both cohorts. No COVID-19 cases were documented in controls, and one case occurred in patient cohort. All previously reported adverse effects resolved. Taken together, the pattern of immunogenicity, efficacy, and safety of BNT162b2 in patients with cancer with solid tumors at six months postvaccination resembles that of the general population. Significance: Evidence regarding efficacy and safety of COVID-19 vaccines in patients with cancer indicate a favorable short-term profile. Immunomodulation due to anticancer treatments may affect immunity and immunogenicity of patients with cancer to the BNT162b2 vaccine over time. Our study sheds light on these long-term outcomes and portrays a trend that resembles the general population. This article is highlighted in the In This Issue feature, p. 2355
Epidemiologically Linked COVID-19 Outbreaks at a Youth Camp and Men’s Conference — Illinois, June–July 2021
Authors: James Matthias, Sarah Patrick, Ann Wiringa, Amanda Pullman, Stephanie Hinton, Jon Campos, Terri Belville, Mallory Sinner, MPH, Torrie T. Buchanan, Bryan Sim, Kristin E. Goldesberry
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Persons with positive SARS-CoV-2 test results were instructed to isolate in
Spherical Nucleic Acid Vaccine Structure Markedly Influences Adaptive Immune Responses of Clinically Utilized Prostate Cancer Targets
Authors: Michelle H. Teplensky, Jasper W. Dittmar, Lei Qin, Shuya Wang, Michael Evangelopoulos, Bin Zhang, Chad A. Mirkin
Journal: Advanced Healthcare Materials (2021)

Abstract Cancer vaccines, which activate the immune system against a target antigen, are attractive for prostate cancer, where multiple upregulated protein targets are identified. However, many clinical trials implementing peptides targeting these proteins have yielded suboptimal results. Using spherical nucleic acids (SNAs), we explore how precise architectural control of vaccine components can activate a robust antigen‐specific immune response in comparison to clinical formulations of the same targets. The SNA vaccines incorporate peptides for human prostate‐specific membrane antigen (PSMA) or T‐cell receptor γ alternate reading frame protein (TARP) into an optimized architecture, resulting in high rates of immune activation and cytolytic ability in humanized mice and human peripheral blood mononuclear cells (hPBMCs). Specifically, administered SNAs elevate the production and secretion of cytokines and increase polyfunctional cytotoxic T cells and effector memory. Importantly, T cells raised from immunized mice potently kill targets, including clinically relevant cells expressing the whole PSMA protein. Treatment of hPBMCs increases costimulatory markers and cytolytically active T cells. This work demonstrates the importance of vaccine structure and its ability to reformulate and elevate clinical targets. Moreover, it encourages the field to reinvestigate ineffective peptide targets and repackage them into optimally structured vaccines to harness antigen potency and enhance clinical outcomes.
Abstract 16334: Conditional Kidney-Specific Knockout of ADAM17 Causes Arterial Stiffness and Hypertension
Authors: Kai Chen, Wang Shirley, Zhongjie Sun
Journal: Circulation (2019)

Objective: ADAM metallopeptidase domain 17 (ADAM17) is a 70-kDa enzyme that belongs to the ADAM protein family of disintegrins and metalloproteases. The objective of this study is to investigate wh...
Research methodologies to address clinical unmet needs and challenges in alcohol‐associated liver disease
Authors: Ashwani K. Singal, Paul Kwo, Allison Kwong, Suthat Liangpunsakul, Alexandre Louvet, Pranoti Mandrekar, Craig McClain, Jessica Mellinger, Gyongyi Szabo, Norah Terrault, Mark Thursz, Gerald S. Winder, W. Ray Kim, Vijay H. Shah
Journal: Hepatology (2021)

Abstract Alcohol‐associated liver disease (ALD) is emerging worldwide as the leading cause of liver‐related morbidity, mortality, and indication for liver transplantation. The ALD Special Interest Group and the Clinical Research Committee at the digital American Association for the Study of Liver Diseases meeting in November 2020 held the scientific sessions to identify clinical unmet needs in ALD, and addressing these needs using clinical research methodologies. Of several research methodologies, the sessions were focused on (a) studying disease burden of ALD using large administrative databases, (b) developing biomarkers for noninvasive diagnosis of alcohol‐associated hepatitis (AH) and estimation of disease prognosis, (c) identifying therapeutic targets for ALD and AH, (d) deriving accurate models to predict prognosis or posttransplant alcohol relapse as a basis for developing treatment algorithm and a uniform protocol on patient‐selection criteria for liver transplantation, and (e) examining qualitative research methodologies in studying the barriers to implementation of multidisciplinary integrated care model by hepatology and addiction teams for the management of dual pathology of liver disease and of alcohol use disorder. Prospective multicenter studies are required to address many of these clinical unmet needs. Further, multidisciplinary care models are needed to improve long‐term outcomes in patients with ALD.
The clinical characterization of the adult patient with an anxiety or related disorder aimed at personalization of management
Authors: Dan J. Stein, Michelle G. Craske, Barbara O. Rothbaum, Samuel R. Chamberlain, Naomi A. Fineberg, Karmel W. Choi, Peter de Jonge, David S. Baldwin, Mario Maj
Journal: World Psychiatry (2021)

The clinical construct of "anxiety neurosis" was broad and poorly defined, so that the delineation of specific anxiety disorders in the DSM-III was an important advance. However, anxiety and related disorders are not only frequently comorbid, but each is also quite heterogeneous; thus diagnostic manuals provide only a first step towards formulating a management plan, and the development of additional decision support tools for the treatment of anxiety conditions is needed. This paper aims to describe systematically important domains that are relevant to the personalization of management of anxiety and related disorders in adults. For each domain, we summarize the available research evidence and review the relevant assessment instruments, paying special attention to their suitability for use in routine clinical practice. We emphasize areas where the available evidence allows the clinician to personalize the management of anxiety conditions, and we point out key unmet needs. Overall, the evidence suggests that we are becoming able to move from simply recommending that anxiety and related disorders be treated with selective serotonin reuptake inhibitors, cognitive-behavioral therapy, or their combination, to a more complex approach which emphasizes that the clinician has a broadening array of management modalities available, and that the treatment of anxiety and related disorders can already be personalized in a number of important respects.
Effect of Empagliflozin on Worsening Heart Failure Events in Patients With Heart Failure and Preserved Ejection Fraction: EMPEROR-Preserved Trial
Authors: Milton Packer, Javed Butler, Faiez Zannad, Gerasimos Filippatos, Joao Pedro Ferreira, Stuart J. Pocock, Peter Carson, Inder Anand, Wolfram Doehner, Markus Haass, Michel Komajda, Alan Miller, Steen Pehrson, John R. Teerlink, Sven Schnaidt, Cordula Zeller, Janet M. Schnee, Stefan D. Anker
Journal: Circulation (2021)

Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with preserved ejection fraction, but additional data are needed about its effect on inpatient and outpatient heart failure events.We randomly assigned 5988 patients with class II through IV heart failure with an ejection fraction of >40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to usual therapy, for a median of 26 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite end points.Empagliflozin reduced the combined risk of cardiovascular death, hospitalization for heart failure, or an emergency or urgent heart failure visit requiring intravenous treatment (432 versus 546 patients [empagliflozin versus placebo, respectively]; hazard ratio, 0.77 [95% CI, 0.67-0.87]; P<0.0001). This benefit reached statistical significance at 18 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (hazard ratio, 0.71 [95% CI, 0.52-0.96]; P=0.028) and the total number of all hospitalizations that required a vasopressor or positive inotropic drug (hazard ratio, 0.73 [95% CI, 0.55-0.97]; P=0.033). Compared with patients in the placebo group, fewer patients in the empagliflozin group reported outpatient intensification of diuretics (482 versus 610; hazard ratio, 0.76 [95% CI, 0.67-0.86]; P<0.0001), and patients assigned to empagliflozin were 20% to 50% more likely to have a better New York Heart Association functional class, with significant effects at 12 weeks that were maintained for at least 2 years. The benefit on total heart failure hospitalizations was similar in patients with an ejection fraction of >40% to <50% and 50% to <60%, but was attenuated at higher ejection fractions.In patients with heart failure with preserved ejection fraction, empagliflozin produced a meaningful, early, and sustained reduction in the risk and severity of a broad range of inpatient and outpatient worsening heart failure events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.
Traditional herbal medicine and nanomedicine: Converging disciplines to improve therapeutic efficacy and human health
Authors: Jing Zhang, Kaili Hu, Liuqing Di, Penglong Wang, Zhidong Liu, Jinming Zhang, Pengfei Yue, Wantong Song, Jingwei Zhang, Tongkai Chen, Zuhua Wang, Yongtai Zhang, Xiaoying Wang, Changyou Zhan, Yung-Chi Cheng, Xiang Li, Quan Li, Jing-Yu Fan, Youqing Shen, Jing-Yan Han, Hongzhi Qiao
Journal: Advanced Drug Delivery Reviews (2021)
Gastrointestinal problems, mechanisms and possible therapeutic directions in Gulf war illness: a mini review
Authors: Diana A. Kimono
Journal: Military Medical Research (2021)

Abstract By its nature, Gulf war illness (GWI) is multisymptomatic and affects several organ systems in the body. Along with other symptoms, veterans who suffer from GWI commonly report chronic gastrointestinal issues such as constipation, pain, indigestion, etc. However, until recently, most attention has been focused on neurological disturbances such as cognitive impairments, chronic fatigue, and chronic pain among affected veterans. With such high prevalence of gastrointestinal problems among Gulf war (GW) veterans, it is surprising that there is little research to investigate the mechanisms behind these issues. This review summarizes all the available works on the mechanisms behind gastrointestinal problems in GWI that have been published to date in various databases. Generally, these studies, which were done in rodent models, in vitro and human cohorts propose that an altered microbiome, a reactive enteric nervous system or a leaky gut among other possible mechanisms are the major drivers of gastrointestinal problems reported in GWI. This review aims to draw attention to the gastrointestinal tract as an important player in GWI disease pathology and a potential therapeutic target.
Telomerase as a therapeutic target in glioblastoma
Authors: Elisa Aquilanti, Lauren Kageler, Patrick Y Wen, Matthew Meyerson
Journal: Neuro-Oncology (2021)

Glioblastoma is the most common primary malignant brain tumor in adults and it continues to have a dismal prognosis. The development of targeted therapeutics has been particularly challenging, in part due to a limited number of oncogenic mutations and significant intra-tumoral heterogeneity. TERT promoter mutations were first discovered in melanoma and later found to be present in up to 80% of glioblastoma samples. They are also frequent clonal alterations in this tumor. TERT promoter mutations are one of the mechanisms for telomerase reactivation, providing cancers with cellular immortality. Telomerase is a reverse transcriptase ribonucleoprotein complex that maintains telomere length in cells with high proliferative ability. In this article, we present genomic and pre-clinical data that support telomerase as a potential "Achilles' heel" for glioblastoma. We also summarize prior experience with anti-telomerase agents and potential new approaches to tackle this target.
High-throughput screening for amyloid-β binding natural small-molecules based on the combinational use of biolayer interferometry and UHPLC−DAD-Q/TOF-MS/MS
Authors: Minsong Guo, Fengdan Zhu, Wenqiao Qiu, Gan Qiao, Betty Yuen-Kwan Law, Lu Yu, Jianming Wu, Yong Tang, Chonglin Yu, Dalian Qin, Xiaogang Zhou, Anguo Wu
Journal: Acta Pharmaceutica Sinica B (2021)

Discovery of drugs rapidly and effectively is an important aspect for Alzheimer's disease (AD). In this study, a novel high-throughput screening (HTS) method aims at screening the small-molecules with amyloid-β (Aβ) binding affinity from natural medicines, based on the combinational use of biolayer interferometry (BLI) and ultra-high-performance liquid chromatography coupled with diode-array detector and quadrupole/time-of-flight tandem mass spectrometry (UHPLC-DAD-Q/TOF-MS/MS) has been firstly developed. Briefly, the components in natural medicines disassociated from biotinylated Aβ were collected to analyze their potential Aβ binding affinity by UHPLC-DAD-Q/TOF-MS/MS. Here, baicalein was confirmed to exhibit the highest binding affinity with Aβ in Scutellaria baicalensis. Moreover, polyporenic acid C (PPAC), dehydrotumulosic acid (DTA), and tumulosic acid (TA) in Kai-Xin-San (KXS) were also identified as potent Aβ inhibitors. Further bioactivity validations indicated that these compounds could inhibit Aβ fibrillation, improve the viability in Aβ-induced PC-12 cells, and decrease the Aβ content and improve the behavioral ability in Caenorhabditis elegans. The molecular docking results confirmed that PPAC, DTA, and TA possessed good binding properties with Aβ. Collectively, the present study has provided a novel and effective HTS method for the identification of natural inhibitors on Aβ fibrillation, which may accelerate the process on anti-AD drugs discovery and development.
Covid-19: “Most complex patient in the world” should have ventilation withdrawn
Authors: Clare Dyer
Journal: BMJ (2021)

A 56 year old woman described by doctors as “the most complex covid patient in the world” should have the ventilation keeping her alive withdrawn by the end of October, a High Court judge has ruled.1

Mr Justice Hayden, vice president of the Court of Protection, said it would be in her best interests to be moved from the intensive care unit to a quiet and private place where she could end her life surrounded by her close family members.

He said he had been told authoritatively that she was the most complex covid patient in the world, in terms of the neurological impact and complications of the disease. That conclusion had been arrived at following consideration of national and international case studies, he added.

The woman, referred to as AH, has been a patient at Addenbrooke’s Hospital in …
Incorporation of Social Risk in US Preventive Services Task Force Recommendations and Identification of Key Challenges for Primary Care
Authors: Karina W. Davidson, Alex H. Krist, Chien-Wen Tseng, Melissa Simon, Chyke A. Doubeni, Alex R. Kemper, Martha Kubik, Quyen Ngo-Metzger, Justin Mills, Amanda Borsky
Journal: JAMA (2021)

In its mission to improve health, the US Preventive Services Task Force (USPSTF) recognizes the strong relationship between a person's health and social and economic circumstances as well as persistent inequities in health care delivery.To assess how social risks have been considered in USPSTF recommendation statements and identify current gaps in evidence needed to expand the systematic inclusion of social risks in future recommendations.The USPSTF commissioned a technical brief that reviewed existing literature on screening and interventions for social risk factors and also audited the 85 USPSTF recommendation statements active as of December 2019 to determine how social risks were addressed in clinical preventive services recommendations.Among the 85 USPSTF recommendation statements reviewed, 14 were focused on preventive services that considered health-related social risks. Social risks were commonly referenced in parts of USPSTF recommendations, with 57 of 85 recommendations including some comment on social risks within the recommendation statement, although many comments were not separate prevention services. Social risks were commented on in USPSTF recommendations as part of risk assessment, as a marker of worse health outcomes from the condition of focus, as a consideration for clinicians when implementing the preventive service, and as a research need or gap on the topic.This report identified how social risks have been considered in the USPSTF recommendation statements. It serves as a benchmark and foundation for ongoing work to advance the goal of ensuring that health equity and social risks are incorporated in USPSTF methods and recommendations.
Receptivity to a Nurse-Led Symptom Management Intervention Among Highly Symptomatic Patients With Cancer
Authors: Grant A Wintheiser, Kathryn J Ruddy, Jeph Herrin, Parvez A Rahman, Deirdre R Pachman, Aaron L Leppin, Lila J Finney Rutten, Minji K Lee, Joan M Griffin, Cindy Tofthagen, Linda L Chlan, Jennifer L Ridgeway, Sandra A Mitchell, Andrea L Cheville
Journal: JNCI Journal of the National Cancer Institute (2021)

The symptom burden associated with cancer and its treatment can negatively affect patients' quality of life and survival. Symptom-focused collaborative care model (CCM) interventions can improve outcomes, but only if patients engage with them. We assessed the receptivity of severely symptomatic oncology patients to a remote nurse-led CCM intervention.In a pragmatic, cluster-randomized, stepped-wedge trial conducted as part of the National Cancer Institute IMPACT Consortium (E2C2, NCT03892967), patients receiving cancer care were asked to rate their sleep disturbance, pain, anxiety, emotional distress, fatigue, and limitations in physical function. Patients reporting at least 1 severe symptom (≥7/10) were offered phone consultation with a nurse symptom care manager (RN SCM). Initially, patients had to "opt-in" to receive a call, but the protocol was later modified so they had to "opt-out" if they did not want a call. We assessed the impact of opt-in vs opt-out framing and patient characteristics on receptiveness to RN SCM calls. All statistical tests were 2-sided.Of the 1204 symptom assessments (from 864 patients) on which at least 1 severe symptom was documented, 469 (39.0%) indicated receptivity to an RN SCM phone call. The opt-out period (odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.12 to 2.32, P = .01), receiving care at a tertiary care center (OR = 3.59, 95% CI = 2.18 to 5.91, P < .001), and having severe pain (OR = 1.80, 95% CI = 1.24 to 2.62, P = .002) were associated with statistically significantly greater willingness to receive a call.Many severely symptomatic patients were not receptive to an RN SCM phone call. Better understanding of reasons for refusal and strategies for improving patient receptivity are needed.
Dynamic Metabolic Risk Profiling of World Trade Center Lung Disease: A Longitudinal Cohort Study
Authors: Sophia Kwon, Myeonggyun Lee, George Crowley, Theresa Schwartz, Rachel Zeig-Owens, David J. Prezant, Mengling Liu, Anna Nolan
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Metabolic syndrome (MetSyn) increases the risk of World Trade Center (WTC) lung injury (LI). However, the temporal relationship of MetSyn, exposure intensity, and lung dysfunction is not well understood. Objective: To model the association of longitudinal MetSyn characteristics with WTC lung disease to define modifiable risk. Methods: Firefighters, for whom consent was obtained (N = 5,738), were active duty on September 11, 2001 (9/11). WTC-LI (n = 1,475; FEV1% predicted <lower limit of normal [LLN]) and non-WTC-LI (n = 4,263; FEV1% predicted ⩾LLN at all exams) was the primary outcome, and FVC% predicted <LLN and FEV1/FVC <0.70 were secondary outcomes. We assessed 1) the effect of concurrent MetSyn on longitudinal lung function by linear mixed models, 2) the temporal effect of MetSyn and exposure by Weibull proportional hazards, 3) the effects of MetSyn's rate of change by two-stage models, and 4) the nonlinear joint effect of longitudinal MetSyn components by a partially linear single-index model (PLSI). Measurements and Main Results: WTC-LI cases were more often ever-smokers, arrived in the morning (9/11), and had MetSyn. Body mass index ⩾30 kg/m2 and high-density lipoprotein <40 mg/dl were most contributory to concurrent loss of FEV1% predicted and FVC% predicted while conserving FEV1/FVC. Body mass index ⩾30 kg/m2 and dyslipidemia significantly predicted WTC-LI, FVC% predicted <LLN in a Weibull proportional hazards model. Dynamic risk assessment of WTC-LI on the basis of MetSyn and exposure showed how reduction of MetSyn factors further reduces WTC-LI likelihood in susceptible populations. PLSI demonstrates that MetSyn has a nonlinear relationship with WTC lung disease, and increases in cumulative MetSyn risk factors exponentially increase WTC-LI risk. An interactive metabolic-risk modeling application was developed to simplify PLSI interpretation. Conclusions: MetSyn and WTC exposure contribute to the development of lung disease. Dynamic risk assessment may be used to encourage treatment of MetSyn in susceptible populations. Future studies will focus on dietary intervention as a disease modifier.