tbuckley/cabot-search huggingface dataset:
Impact of Pembrolizumab Versus Chemotherapy as Second-Line Therapy for Advanced Esophageal Cancer on Health-Related Quality of Life in KEYNOTE-181
Authors: Antoine Adenis, Amit S. Kulkarni, Gustavo C. Girotto, Christelle de la Fouchardiere, Helene Senellart, Hanneke W. M. van Laarhoven, Wasat Mansoor, Raed Al-Rajabi, Josephine Norquist, Mayur Amonkar, Shailaja Suryawanshi, Pooja Bhagia, Jean-Philippe Metges
Journal: Journal of Clinical Oncology (2021)

In the phase III KEYNOTE-181 study (NCT02564263) of patients with advanced esophageal cancer (EC), pembrolizumab monotherapy prolonged overall survival versus chemotherapy as second-line therapy in patients with programmed death ligand 1 combined positive score (CPS) ≥ 10. We present the results of the prespecified health-related quality-of-life (HRQoL) analyses of the squamous cell carcinoma (SCC), CPS ≥ 10, and CPS ≥ 10 SCC populations.HRQoL was measured using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ EC questionnaire (OES18), and EuroQol 5-dimension questionnaire (EQ-5D). Data were analyzed in patients who received ≥ 1 dose of study treatment and completed ≥ 1 HRQoL assessment. Key analyses included baseline to week 9 least squares mean change in global health status/quality of life, functional or symptom subscales, and time to deterioration (≥ 10-point deterioration) for specific subscales.The HRQoL population included 387 patients with SCC. Compliance and completion rates for all three questionnaires were similar in both treatment groups at baseline and week 9. No clinically meaningful differences in global health status/quality of life scores were observed between treatment groups from baseline to week 9 (least squares mean difference, 2.80; 95% CI, -1.48 to 7.08); patients in both treatment groups generally exhibited stable functioning and symptom scores of the QLQ-C30 and QLQ-OES18 from baseline to week 9. Time to deterioration for pain (hazard ratio [HR], 1.22; 95% CI, 0.79 to 1.89), reflux (HR, 2.38; 95% CI, 1.33 to 4.25), and dysphagia (HR, 1.53; 95% CI, 1.02 to 2.31) subscales were similar between treatment groups. These findings were generally similar in the CPS ≥ 10 (n = 218) and CPS ≥ 10 SCC (n = 166) subgroups.In patients with advanced EC, pembrolizumab monotherapy and chemotherapy maintained HRQoL in patients with SCC, CPS ≥ 10, and CPS ≥ 10 SCC.
Germline HLA-B evolutionary divergence influences the efficacy of immune checkpoint blockade therapy in gastrointestinal cancer
Authors: Zhihao Lu, Huan Chen, Xi Jiao, Yujiao Wang, Lijia Wu, Huaibo Sun, Shuang Li, Jifang Gong, Jian Li, Jianling Zou, Keyan Yang, Ying Hu, Beibei Mao, Lei Zhang, Xiaotian Zhang, Zhi Peng, Ming Lu, Zhenghang Wang, Henghui Zhang, Lin Shen
Journal: Genome Medicine (2021)

Abstract Background The human leukocyte antigen class I (HLA-I) genotype has been linked with differential immune responses to infectious disease and cancer. However, the clinical relevance of germline HLA-mediated immunity in gastrointestinal (GI) cancer remains elusive. Methods This study retrospectively analyzed the genomic profiling data from 84 metastatic GI cancer patients treated with immune checkpoint blockade (ICB) recruited from Peking University Cancer Hospital (PUCH). A publicly available dataset from the Memorial Sloan Kettering (MSK) Cancer Center (MSK GI cohort) was employed as the validation cohort. For the PUCH cohort, we performed HLA genotyping by whole exome sequencing (WES) analysis on the peripheral blood samples from all patients. Tumor tissues from 76 patients were subjected to WES analysis and immune oncology-related RNA profiling. We studied the associations of two parameters of germline HLA as heterozygosity and evolutionary divergence (HED, a quantifiable measure of HLA-I evolution) with the clinical outcomes of patients in both cohorts. Results Our data showed that neither HLA heterozygosity nor HED at the HLA-A/HLA-C locus correlated with the overall survival (OS) in the PUCH cohort. Interestingly, in both the PUCH and MSK GI cohorts, patients with high HLA-B HED showed a better OS compared with low HLA-B HED subgroup. Of note, a combinatorial biomarker of HLA-B HED and tumor mutational burden (TMB) may better stratify potential responders. Furthermore, patients with high HLA-B HED were characterized with a decreased prevalence of multiple driver gene mutations and an immune-inflamed phenotype. Conclusions Our results unveil how HLA-B evolutionary divergence influences the ICB response in patients with GI cancers, supporting its potential utility as a combinatorial biomarker together with TMB for patient stratification in the future.
Antibiotics versus Appendectomy for Acute Appendicitis — Longer-Term Outcomes
Authors: Giana H Davidson, David R Flum, Sarah E Monsell, Lillian S Kao, Emily C Voldal, Patrick J Heagerty, Erin Fannon, Danielle C Lavallee, Bonnie Bizzell, Sarah O Lawrence, Bryan A Comstock, Anusha Krishnadasan, Robert J Winchell, Wesley H Self, Callie M Thompson, Farhood Farjah, Pauline K Park, Hasan B Alam, Darin Saltzman, Gregory J Moran, Amy H Kaji, Daniel A DeUgarte, Matthew Salzberg, Lisa Ferrigno, Katherine A Mandell, Thea P Price, Nicole Siparsky, Jacob Glaser, Patricia Ayoung-Chee, William Chiang, Jesse Victory, Bruce Chung, Damien W Carter, Matthew E Kutcher, Alan Jones, Julie Holihan, Mike K Liang, Brett A Faine, Joseph Cuschieri, Heather L Evans, Jeffrey Johnson, Joe H Patton, Natasha Coleman, Katherine Fischkoff, F Thurston Drake, Sabrina E Sanchez, Charles Parsons, Stephen R Odom, Larry G Kessler, David A Talan
Journal: New England Journal of Medicine (2021)
TCT-402 One-Year Outcomes of Transcatheter Mitral Valve-in-Valve Replacement
Authors: Ramsey Kalil, Yemisi Adejumo, S. Chiu Wong, Geoffrey Bergman, Luke Kim, Dmitriy Feldman, Harsimran Singh, Stephanie Mick, Erin Iannacone, Robert Minutello
Journal: Journal of the American College of Cardiology (2021)
TCT-145 Temporal Trends and Hospital Variation in Pacemaker Implantation Following TAVR—Insights From the STS/ACC TVT Registry
Authors: Amit Vora, Hemal Gada, Pratik Manandhar, Andrzej Kosinski, Ajay Kirtane, Tamim Nazif, Michael Reardon, Susheel Kodali, David Cohen, Vinod Thourani, Matthew Sherwood, Howard Julien, Sreekanth Vemulapalli
Journal: Journal of the American College of Cardiology (2021)
IgA Nephropathy Post COVID-19 Infection
Authors: Zachary Drury, Laith Al-Rabadi, Martin C. Gregory, Sarah Gilligan, Ritika Ohri, Monica P. Revelo Penafiel, Josephine Abraham
Journal: Journal of the American Society of Nephrology (2021)

Drury, Zachary; Al-Rabadi, Laith; Gregory, Martin C.; Gilligan, Sarah; Ohri, Ritika; Revelo Penafiel, Monica P.; Abraham, Josephine Author Information
Highlights from the American Medical Society for Sports Medicine position statement on responsible use of regenerative medicine and orthobiologics in sports medicine
Authors: Shane A Shapiro, Jonathan T Finnoff, Tariq M Awan, Joanne P Borg-Stein, Kimberly G Harmon, Daniel C Herman, Gerard Malanga, Zubin Master, Kenneth Mautner
Journal: British Journal of Sports Medicine (2021)

Musculoskeletal conditions including osteoarthritis and chronic tendinopathies are leading causes of pain and disability worldwide. The emergence of novel regenerative therapies, referred to as orthobiologics, has led to promising interventions which may reduce pain and improve function. Orthobiologics are biological substances intended to enhance healing and alter the natural course of orthopaedic disease.1 2 Despite growing experience, the field remains under-researched with inconsistent evidence; yet increasing enthusiasm has permitted overexuberant, sometimes inappropriate use with proliferation of misinformation among both providers and patients.

An American Medical Society for Sports Medicine (AMSSM) position statement was developed to help sports medicine physicians make informed and responsible decisions about the role of regenerative medicine in their practice.3 The statement contains relevant terminology, review of basic and clinical science, ethics, regulations and best practices for considering regenerative medicine in clinical practice (figure 1). The statement seeks to educate physicians regarding a broad and emerging discipline and is not an endorsement by AMSSM of any specific product or procedure.



Figure 1 
Responsible use of orthobiologics and other novel regenerative therapies requires multiple considerations before translation into routine clinical practice.



Regenerative medicine is rapidly growing with terms and definitions yet to be standardised. While originating with stem cell discovery and translation, regenerative therapies, of which orthobiologics is but one category, are no longer a single platform technology. Rather, they now encompass a heterogeneous collection of biological sources with varying activity that hold the potential to transform human health. Common orthobiologics employed in research and clinical practice are being conflated under the umbrella of ‘stem cell’ therapy in a …
Rational design of non-toxic GOx-based biocatalytic nanoreactor for multimodal synergistic therapy and tumor metastasis suppression
Authors: Lifeng Hang, Tao Zhang, Hua Wen, Meng Li, Lianbao Liang, Xinfeng Tang, Chunze Zhou, JunZhang Tian, Xiaofen Ma, Guihua Jiang
Journal: Theranostics (2021)

Rationale: Glucose oxidase (GOx)-based biocatalytic nanoreactors can cut off the energy supply of tumors for starvation therapy and deoxygenation-activated chemotherapy. However, these nanoreactors, including mesoporous silica, calcium phosphate, metal-organic framework, or polymer nanocarriers, cannot completely block the reaction of GOx with glucose in the blood, inducing systemic toxicity from hydrogen peroxide (H2O2) and anoxia. The low enzyme loading capacity can reduce systemic toxicity but limits its therapeutic effect. Here, we describe a real 'ON/OFF' intelligent nanoreactor with a core-shell structure (GOx + tirazapamine (TPZ))/ZIF-8@ZIF-8 modified with the red cell membrane (GTZ@Z-RBM) for cargo delivery. Methods: GTZ@Z-RBM nanoparticles (NPs) were prepared by the co-precipitation and epitaxial growth process under mild conditions. The core-shell structure loaded with GOx and TPZ was characterized for hydrate particle size and surface charge. The GTZ@Z-RBM NPs morphology, drug, and GOx loading/releasing abilities, system toxicity, multimodal synergistic therapy, and tumor metastasis suppression were investigated. The in vitro and in vivo outcomes of GTZ@Z-RBM NPs were assessed in 4T1 breast cancer cells. Results: GTZ@Z-RBM NPs could spatially isolate the enzyme from glucose in a physiological environment, reducing systemic toxicity. The fabricated nanoreactor with high enzyme loading capacity and good biocompatibility could deliver GOx and TPZ to the tumors, thereby exhausting glucose, generating H2O2, and aggravating hypoxic microenvironment for starvation therapy, DNA damage, and deoxygenation-activated chemotherapy. Significantly, the synergistic therapy effectively suppressed the breast cancer metastasis in mice and prolonged life without systemic toxicity. The in vitro and in vivo results provided evidence that our biomimetic nanoreactor had a powerful synergistic cascade effect in treating breast cancer. Conclusion: GTZ@Z-RBM NPs can be used as an 'ON/OFF' intelligent nanoreactor to deliver GOx and TPZ for multimodal synergistic therapy and tumor metastasis suppression.
Single Cell Analysis Reveals Deeper Insight of the Gateway Cell Type for SARS-CoV-2 in Kidney
Authors: Yuxiang Sun, Hongchun Lin, Xinxin Ma, Qiang Huang, Hui Peng
Journal: Journal of the American Society of Nephrology (2021)

Journal of the American Society of Nephrology 32(10S):p 57-58, October 2021. | DOI: 10.1681/ASN.20213210S157d
Humoral Response to Pfizer BNT162b2 in Peritoneal and Hemodialysis Patients: A Comparative Study
Authors: Rui A. Duarte, Marisa Roldão, Cátia R. Figueiredo, Francisco Ferrer, Hernâni M. Gonçalves, Flora Sofia, Ivan A. Luz
Journal: Journal of the American Society of Nephrology (2021)

Duarte, Rui A.; Roldão, Marisa; Figueiredo, Cátia R.; Ferrer, Francisco; Gonçalves, Hernâni M.; Sofia, Flora; Luz, Ivan A. Author Information
Regional Disparities in Obesity Among a Heterogeneous Population of Chinese Children and Adolescents
Authors: Li Zhang, JingNan Chen, JianWei Zhang, Wei Wu, Ke Huang, RuiMin Chen, Mireguli Maimaiti, ShaoKe Chen, BingYan Cao, Min Zhu, ChunLin Wang, Zhe Su, Yan Liang, Hui Yao, HaiYan Wei, RongXiu Zheng, HongWei Du, FeiHong Luo, Pin Li, MinJia Mo, YunXian Yu, Ergang Wang, Robert M. Dorazio, Junfen Fu
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Obesity is a public health challenge in China, but the geographical profiles of overweight and obesity among Chinese children are limited. <h3>Objective</h3> To examine regional disparities in the prevalence of obesity among the heterogeneous population of Chinese children and adolescents to provide a more accurate profile of obesity among children in China. <h3>Design, Setting, and Participants</h3> The Prevalence and Risk Factors for Obesity and Diabetes in Youth (PRODY) study was a cross-sectional survey study conducted from January 1, 2017, to December 31, 2019, among 201 098 children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that produced a sample of Chinese children with a full range of ages and wide geographical coverage using a multistage, stratified, cluster-sampling design. <h3>Exposures</h3> Five regions geographically representative of China (northern, eastern, southern, western, and central). <h3>Main Outcomes and Measures</h3> The body weights and heights of all participants were measured. Multilevel, multinomial logistic regression models were used to estimate the prevalence of overweight and obesity. <h3>Results</h3> Among 201 098 healthy children (105 875 boys [52.6%]; mean [SD] age, 9.8 [3.8] years) from eastern, southern, northern, central, and western China, the highest obesity prevalence was estimated for children aged 8 to 13 years in northern China (from 18.8% [95% CI, 16.2%-21.7%] to 23.6% [95% CI, 20.5%-26.9%]) and for boys aged 3 to 6 years in western China (from 18.1% [95% CI, 10.4%-29.4%] to 28.6% [95% CI, 14.3%-49.0%]). Boys had a higher prevalence than girls of obesity only in eastern and northern China, with a mean difference in prevalence of 4.6% (95% CI, 3.8%-5.4%) and 7.6% (95% CI, 6.5%-8.6%), respectively. <h3>Conclusions and Relevance</h3> In this survey study, substantial geographic disparities in the prevalence of obesity and overweight were found among the heterogeneous population of Chinese children. The results suggest that special attention should be paid to vulnerable children and that regionally adapted interventions are needed to efficiently mitigate obesity in children.
Abstract 11793: Impaired Autophagic Off-rate is Responsible for Cardiac Aging via Oxidative Stress
Authors: Yasuko K Bando, Takahiro Kamihara, Kazuyuki Nishimura, Yasheng Retina, Toyoaki Murohara
Journal: Circulation (2019)

Introduction: Cardiac aging is the primary causes of heart failure. More interestingly, DNA damage causes systemic autophagic disorder that is responsible for development of aging phenotype in prog...
Pembrolizumab Plus Vorinostat Induces Responses in Patients with Hodgkin Lymphoma Who Are Refractory to Prior PD-1 Blockade
Authors: Alex F. Herrera, Lu Chen, L. Elizabeth Budde, Saro Armenian, Liana Nikolaenko, Robert Chen, Shari Daniels, Neena Kennedy, Lacolle Peters, Steven T. Rosen, Stephen J Forman, Leslie L. Popplewell, Larry W. Kwak, Matthew Mei
Journal: Blood (2021)
Preliminary Report of a Multicenter Cohort Study of Myocardial Viability Assessment by Gated 99m Tc-Sestamibi SPECT at Rest
Authors: Kuwabara Yoichi, Komuro Issei, Nakajima Kenichi, Taki Junichi, Matsunari Ichiro, Kawano Masaya, Nishimura Shigeyuki, Yamashina Akira, Ishida Yoshio, Morita Koichi, Tamaki Nagara, Tomoike Hitonobu
Journal: Circulation (2007)
Aetiology of tinea capitis in China: a multicentre prospective study
Authors: X.-Q. Chen, D.-Y. Zheng, Y.-Y. Xiao, B.-L. Dong, C.-W. Cao, L. Ma, Z.-S. Tong, M. Zhu, Z.-H. Liu, L.-Y. Xi, M. Fu, Y. Jin, B. Yin, F.-Q. Li, X.-F. Li, P. Abliz, H.-F. Liu, Y. Zhang, N. Yu, W.-W. Wu, X.-C. Xiong, J.-S. Zeng, H.-Q. Huang, Y.-P. Jiang, G.-Z. Chen, W.-H. Pan, H. Sang, Y. Wang, Y. Guo, D.-M. Shi, J.-X. Yang, W. Chen, Z. Wan, R.-Y. Li, A.-P. Wang, Y.-P. Ran, J. Yu
Journal: British Journal of Dermatology (2021)

Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time.This study aimed to clarify the current epidemiological characteristics and pathogen spectrum of tinea capitis in China.A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory.Among all enrolled patients, 74·1% of the cases were in patients aged 2-8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province.Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.
GRAd-COV2, a gorilla adenovirus-based candidate vaccine against COVID-19, is safe and immunogenic in younger and older adults
Authors: Simone Lanini, Stefania Capone, Andrea Antinori, Stefano Milleri, Emanuele Nicastri, Roberto Camerini, Chiara Agrati, Concetta Castilletti, Federica Mori, Alessandra Sacchi, Giulia Matusali, Roberta Gagliardini, Virginia Ammendola, Eleonora Cimini, Fabiana Grazioli, Laura Scorzolini, Federico Napolitano, Maria M. Plazzi, Marco Soriani, Aldo De Luca, Simone Battella, Andrea Sommella, Alessandra M. Contino, Federica Barra, Michela Gentile, Angelo Raggioli, Yufang Shi, Enrico Girardi, Markus Maeurer, Maria R. Capobianchi, Francesco Vaia, Mauro Piacentini, Guido Kroemer, Alessandra Vitelli, Stefano Colloca, Antonella Folgori, Giuseppe Ippolito
Journal: Science Translational Medicine (2021)

GRAd-COV2, a candidate vaccine for COVID-19 based on a gorilla adenovirus, is safe and immunogenic in younger and older adults.
Abstract 16306: Impact of Aortic Valve Calcification on Acute Elastic Recoil of a Balloon-Expandable Valve After Transcatheter Aortic Valve Replacement
Authors: Nagataka Yoshihara, Hirokuni Akahori, Takamasa Tanaka, Koji Yanaka, Toshio Kimura, Kojiro Miki, Takahiro Imanaka, Masaharu Ishihara
Journal: Circulation (2019)

Background and Aim: It has been known that acute elastic recoil of coronary stent is affected by calcification of coronary atherosclerotic lesions. The aim of this study was to investigate the impa...
The Recent Rise of Suicide Mortality in the United States
Authors: Gonzalo Martínez-Alés, Tammy Jiang, Katherine M. Keyes, Jaimie L. Gradus
Journal: Annual Review of Public Health (2021)

Suicide is a major public health concern in the United States. Between 2000 and 2018, US suicide rates increased by 35%, contributing to the stagnation and subsequent decrease in US life expectancy. During 2019, suicide declined modestly, mostly owing to slight reductions in suicides among Whites. Suicide rates, however, continued to increase or remained stable among all other racial/ethnic groups, and little is known about recent suicide trends among other vulnerable groups. This article (
Three-Month Clinical, Functional, and Mental Outcomes in Kidney Transplant Recipients Surviving COVID-19
Authors: Raphael Duivenvoorden, Priya Vart, Marlies Noordzij, Augusto Cesar Soares dos Santos, Alex B. Zulkarnaev, Casper F. Franssen, Dirk R. Kuypers, Erol Demir, Hormat Rahimzadeh, Julia Kerschbaum, Kitty J. Jager, Kultigin Turkmen, Marc H. Hemmelder, Marcel Schouten, María L. Rodríguez-Ferrero, Marta Crespo, Ron T. Gansevoort, Luuk Hilbrands
Journal: Journal of the American Society of Nephrology (2021)

Background: Kidney transplant patients are at high risk for COVID-19 related mortality. However, limited data are available on longer term clinical, functional and mental outcomes in patients that survive COVID-19. Methods: Data from adult kidney transplant patients that presented with COVID-19 between February 1st, 2020 and January 31st, 2021 were retrieved from the ERACODA database. Data from patients with complete data for vital status, hospitalization and/or ICU admission was used for this analysis. Results: 912 patients were included with a mean age of 56.7 (±13.7) years. 26.4% were not hospitalized, 57.5% hospitalized, and 16.1% hospitalized and ICU admitted. Three-months survival was 82.3% overall and 98.8%, 84.2% and 49.0% resp. in each group. Three-months acute rejection, need for dialysis / CVVH at any time point, and graft failure occurred in the overall group in 1.0%, 2.6% and 1.8% resp., and in 2.1%, 10.6% and 10.6% of ICU admitted patients resp. Of the surviving patients 83.3% had reached their prior functional status within 3 months. Of patients that had not yet reached their prior functional status, it was expected that 79.6% still would do so within the coming year. 94.4% had reached their prior mental status. Of patients that had not yet reached their prior mental status, it was expected that 80% of patients would do so within the coming year. Conclusions: In patients alive at three-months follow-up, graft loss was rare, and most patients had reached their pre-COVID-19 functional and mental status. Clinical, functional, and mental outcomes in kidney transplant recipients three months after being diagnosed with COVID-19. Data of 487 patients were available for analysis of graft function related outcomes. Data of 450 patients were available for functional and mental status outcomes.