tbuckley/cabot-search huggingface dataset:
A Low Tumor Mutational Burden and <i>PTEN</i> Mutations Are Predictors of a Negative Response to PD-1 Blockade in MSI-H/dMMR Gastrointestinal Tumors
Authors: Keigo Chida, Akihito Kawazoe, Masahito Kawazu, Toshihiro Suzuki, Yoshiaki Nakamura, Tetsuya Nakatsura, Takeshi Kuwata, Toshihide Ueno, Yasutoshi Kuboki, Daisuke Kotani, Takashi Kojima, Hiroya Taniguchi, Hiroyuki Mano, Masafumi Ikeda, Kohei Shitara, Itaru Endo, Takayuki Yoshino
Journal: Clinical Cancer Research (2021)

This study performed a comprehensive molecular characterization of microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) gastrointestinal (GI) tumors to elucidate predictors of response to PD-1 blockade.Forty-five patients with MSI-H/dMMR GI tumors, including gastric cancer, colorectal cancer, cholangiocarcinoma, small intestine cancer, pancreatic cancer, and duodenal cancer, receiving PD-1 blockade were analyzed. We conducted the genomic profiling of GI tumors by whole-exome sequencing or targeted next-generation sequencing. The tumor microenvironment was evaluated by transcriptomic analysis and multiplex fluorescence IHC.Patients with low tumor mutational burdens (TMBs) had lower objective response rates (ORRs; 0% vs. 48.8%) and a significantly shorter progression-free survival (PFS; 2.3 vs. 15.6 months; HR, 6.20; P = 0.002) than those with high TMBs. Among common gene alterations in GI tumors, only PTEN mutations, which were mutually exclusive with a low TMB, were significantly associated with a lower ORRs than wild-type PTEN (21.4 vs. 54.8%; odds, 4.45; P = 0.045). Compared with wild-type PTEN, PTEN mutations in the phosphatase domain were associated with significantly lower ORRs (12.5 vs. 54.8%; P = 0.049), shorter PFS (2.6 vs. 15.6 months; HR, 5.04; P < 0.001), lower intratumoral CD8+ T-cell levels, higher intratumoral CD204+ macrophage levels, and PI3K/AKT/mTOR pathway enrichment, whereas PTEN mutations in the C2 domain were not.Low TMBs and PTEN mutations, especially mutations in the phosphatase domain associated with an immunosuppressive environment, were mutually exclusive and might be negative predictors of PD-1 blockade responses in patients with MSI-H/dMMR GI tumors.
Abstract 17960: Differential Impairment of Adherence-Junction Expression/Phosphorylation of Human Myocardium in the Setting of Diabetes After Cardioplegia
Authors: Jun Feng, Yuhong Liu, Nikola Dobrilovic, Arun K Singh, Cesario Bianchi, Frank W Sellke
Journal: Circulation (2013)

Background: Previous experimental and clinical studies have demonstrated that endothelial adherence-junction molecules are significantly altered in the animal and human myocardium and microvasculat...
Linked Clusters of SARS-CoV-2 Variant B.1.351 — Maryland, January–February 2021
Authors: Kenneth A. Feder, Marcia Pearlowitz, Alexandra Goode, Monique Duwell, Thelonious W. Williams, Ping An Chen-Carrington, Ami Patel, Catherine Dominguez, Eric N. Keller, Liore Klein, Alessandra Rivera-Colon, Heba H. Mostafa, C. Paul Morris, Neil Patel, Anna M. Schauer, Robert Myers, David Blythe, Katherine A. Feldman
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

In late January 2021, a clinical laboratory notified the Maryland Department of Health (MDH) that the SARS-CoV-2 variant of concern B.1.351had been identified in a specimen collected from a Maryland resident with COVID-19 (1).The SARS-CoV-2 B.1.351lineage was first identified in South Africa (2) and might be neutralized less effectively by antibodies produced after vaccination or natural infection with other strains (3-6).To limit SARS-CoV-2 chains of transmission associated with this index patient, MDH used contact tracing to identify the source of infection and any linked infections among other persons.The investigation identified two linked clusters of SARS-CoV-2 infection that included 17 patients.Three additional specimens from these clusters were sequenced; all three had the B.1.351variant and all sequences were closely related to the sequence from the index patient's specimen.Among the 17 patients identified, none reported recent international travel or contact with international travelers.Two patients, including the index patient, had received the first of a 2-dose COVID-19 vaccination series in the 2 weeks before their likely exposure; one additional patient had a confirmed SARS-CoV-2 infection 5 months before exposure.Two patients were hospitalized with COVID-19, and one died.These first identified linked clusters of B.1.351infections in the United States with no apparent link to international travel highlight the importance of expanding the scope and volume of genetic surveillance programs to identify variants, completing contact investigations for SARS-CoV-2 infections, and using universal prevention strategies, including vaccination, masking, and physical distancing, to control the spread of variants of concern.Case investigation, contact elicitation (following CDC guidelines for defining close contacts) (7,8), and contact tracing were conducted for the index patient immediately after the initial diagnostic test result before the sequencing results were available; in Maryland, this is standard procedure for all persons with COVID-19 diagnosed by a SARS-CoV-2 antigen test or nucleic acid amplification test (NAAT) (including reverse transcription-polymerase chain reaction [RT-PCR]).This process was conducted for all COVID-19 cases identified from among the index patient's contacts until no additional cases in the transmission chain could be identified.Interviews of persons with positive test results and their contacts were
Mimicking the Human Tympanic Membrane: The Significance of Scaffold Geometry
Authors: Shivesh Anand, Thomas Stoppe, Mónica Lucena, Timo Rademakers, Marcus Neudert, Serena Danti, Lorenzo Moroni, Carlos Mota
Journal: Advanced Healthcare Materials (2021)

Abstract The human tympanic membrane (TM) captures sound waves from the environment and transforms them into mechanical motion. The successful transmission of these acoustic vibrations is attributed to the unique architecture of the TM. However, a limited knowledge is available on the contribution of its discrete anatomical features, which is important for fabricating functional TM replacements. This work synergizes theoretical and experimental approaches toward understanding the significance of geometry in tissue‐engineered TM scaffolds. Three test designs along with a plain control are chosen to decouple some of the dominant structural elements, such as the radial and circumferential alignment of the collagen fibrils. In silico models suggest a geometrical dependency of their mechanical and acoustical responses, where the presence of radially aligned fibers is observed to have a more prominent effect compared to their circumferential counterparts. Following which, a hybrid fabrication strategy combining electrospinning and additive manufacturing has been optimized to manufacture biomimetic scaffolds within the dimensions of the native TM. The experimental characterizations conducted using macroindentation and laser Doppler vibrometry corroborate the computational findings. Finally, biological studies with human dermal fibroblasts and human mesenchymal stromal cells reveal a favorable influence of scaffold hierarchy on cellular alignment and subsequent collagen deposition.
ASSOCIATION OF WEIGHT GAIN FROM EARLY TO MIDDLE ADULTHOOD WITH RISK OF METABOLIC SYNDROME
Authors: Xiuling Wang, Jiali Song, Yan Gao, Chaoqun Wu, Jianlan Cui, Teng Li, Yang Yang, Jiamin Liu, Jiapeng Lu, Xi Li, Haibo Zhang, Xin Zheng
Journal: Journal of the American College of Cardiology (2021)
EFFICACY AND SAFETY OF HYPERTONIC SALINE SOLUTION WITH FUROSEMIDE IN PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Neha Patel, Mitra Patel, Ahmed Elzanaty, Sapan Bhuta, Cameron Burmeister, Jeremy Tomcho, Sami Ghazaleh
Journal: Journal of the American College of Cardiology (2021)
DIRECT ORAL ANTICOAGULANTS AND WARFARIN: EFFECTIVENESS AND SAFETY OUTCOMES AMONG NONVALVULAR ATRIAL FIBRILLATION PATIENTS WITH MULTIMORBIDITY
Authors: Amol Dhamane, Mauricio Ferri, Allison Keshishian, Cristina Russ, Ruth Thomas, Gary Leung, Birol Emir, Huseyin Yuce, Manuela Di Fusco
Journal: Journal of the American College of Cardiology (2021)
A SCID mouse-human lung xenograft model of SARS-CoV-2 infection
Authors: Wenkun Fu, Wei Wang, Lunzhi Yuan, Yanzhen Lin, Xiumin Huang, Rirong Chen, Minping Cai, Che Liu, Liqiang Chen, Ming Zhou, Kun Wu, Huan Zhao, Dequan Pan, Jian Ma, Junping Hong, Bingke Zhai, Yali Zhang, Zhibo Kong, Yingbin Wang, Yixin Chen, Quan Yuan, Huachen Zhu, Tong Cheng, Yi Guan, Ningshao Xia
Journal: Theranostics (2021)

SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause lifethreatening pneumonia, respiratory failure and even death.Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics.However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for in vitro/in vivo models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures.The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection in vivo.Methods: Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks.Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period.The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts.Results: Human lung xenografts expanded and developed mature structures closely resembling normal human lung.SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response.IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts.Conclusions: These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.
Dexamethasone and Surgical-Site Infection
Authors: Tomás B. Corcoran, Paul S. Myles, Andrew B. Forbes, Allen C. Cheng, Leon A. Bach, Edmond O’Loughlin, Kate Leslie, Matthew T.V. Chan, David Story, Timothy G. Short, Catherine Martin, Pauline Coutts, Kwok M. Ho
Journal: New England Journal of Medicine (2021)

The glucocorticoid dexamethasone prevents nausea and vomiting after surgery, but there is concern that it may increase the risk of surgical-site infection.In this pragmatic, international, noninferiority trial, we randomly assigned 8880 adult patients who were undergoing nonurgent, noncardiac surgery of at least 2 hours' duration, with a skin incision length longer than 5 cm and a postoperative overnight hospital stay, to receive 8 mg of intravenous dexamethasone or matching placebo while under anesthesia. Randomization was stratified according to diabetes status and trial center. The primary outcome was surgical-site infection within 30 days after surgery. The prespecified noninferiority margin was 2.0 percentage points.A total of 8725 participants were included in the modified intention-to-treat population (4372 in the dexamethasone group and 4353 in the placebo group), of whom 13.2% (576 in the dexamethasone group and 572 in the placebo group) had diabetes mellitus. Of the 8678 patients included in the primary analysis, surgical-site infection occurred in 8.1% (354 of 4350 patients) assigned to dexamethasone and in 9.1% (394 of 4328) assigned to placebo (risk difference adjusted for diabetes status, -0.9 percentage points; 95.6% confidence interval [CI], -2.1 to 0.3; P<0.001 for noninferiority). The results for superficial, deep, and organ-space surgical-site infections and in patients with diabetes were similar to those of the primary analysis. Postoperative nausea and vomiting in the first 24 hours after surgery occurred in 42.2% of patients in the dexamethasone group and in 53.9% in the placebo group (risk ratio, 0.78; 95% CI, 0.75 to 0.82). Hyperglycemic events in patients without diabetes occurred in 22 of 3787 (0.6%) in the dexamethasone group and in 6 of 3776 (0.2%) in the placebo group.Dexamethasone was noninferior to placebo with respect to the incidence of surgical-site infection within 30 days after nonurgent, noncardiac surgery. (Funded by the Australian National Health and Medical Research Council and others; PADDI Australian New Zealand Clinical Trials Registry number, ACTRN12614001226695.).
Population-based estimates of breast cancer risk for germline pathogenic variants identified by gene-panel testing: An Australian perspective
Authors: Nguyen-Dumont Tu, James Dowty, Katherine Tucker, Judy Kirk, Paul James, Alison Trainer, Ingrid Winship, Nicholas Pachter, Nicola Poplawski, Scott Grist, Daniel J Park, Anne-Laure Renault, Fleur Hammet, Maryam Mahmoodi, Helen Tsimiklis, Jason A Steen, Derrick Theys, Amanda Rewse, Amanda Willis, April Morrow, Catherine Speechly, Rebecca Harris, Moeen Riaz, Robert Sebra, Eric Schadt, Paul Lacaze, John McNeil, John L Hopper, Melissa C Southey
Journal: Cancer Research (2021)
PATIENT-SPECIFIC COVID-19 RESOURCE UTILIZATION PREDICTION USING FUSION AI MODEL
Authors: Amara Tariq, Leo Celi, Janice Newsome, Saptarchi Purkayastha, Neal Bhatia, Faisal Merchant, Hari Trivedi, Judy Gichoya, Imon Banerjee
Journal: Journal of the American College of Cardiology (2021)
CD40 Agonist Targeted to Fibroblast Activation Protein α Synergizes with Radiotherapy in Murine HPV-Positive Head and Neck Tumors
Authors: Sara Labiano, Vincent Roh, Céline Godfroid, Agnès Hiou-Feige, Jackeline Romero, Eva Sum, Moritz Rapp, Gael Boivin, Tania Wyss, Christian Simon, Jean Bourhis, Pablo Umaña, Christine Trumpfheller, Genrich V. Tolstonog, Marie-Catherine Vozenin, Pedro Romero
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The incidence of human papillomavirus–associated head and neck squamous cell carcinoma (HPV+-HNSCC) is rising worldwide and although current therapeutic modalities are efficient in the majority of patients, there is a high rate of treatment failures. Thus, novel combination approaches are urgently needed to achieve better disease control in patients with HPV+-HNSCC. We investigated the safety and therapeutic efficacy of a novel fibroblast activation protein (FAP)-targeted CD40 agonist (FAP-CD40) in combination with local hypofractionated radiation in a syngeneic HPV+-HNSCC model. Experimental Design: Using an established orthotopic model, we treated tumor-bearing mice with local hypofractionated radiotherapy (2 × 6 Gy) alone or in combination with a systemic administration of the FAP-CD40 antibody. Following up the mice, we evaluated the changes in the tumor microenvironment (TME) by immunofluorescence, FACS, and NanoString RNA analysis. Results: The suboptimal radiotherapy regimen chosen failed to control tumors in the treated mice. The FAP-CD40 administered in monotherapy transiently controlled tumor growth, whereas the combined therapy induced durable complete responses in more than 80% of the tumor-bearing mice. This notable efficacy relied on the radiotherapy-induced remodeling of the TME and activation of the CD8+ T-cell-cDC1 axis and was devoid of the systemic toxicity frequently associated with CD40-targeted therapy. Moreover, the robust immunologic memory developed effectively prevented tumor relapses, a common feature in patients with HNSCC. Conclusions: Our study provides proof of concept, as well as mechanistic insights of the therapeutic efficacy of a bispecific FAP-CD40 combined with local radiotherapy in a FAP+-HNSCC model increasing overall survival and inducing long-term antitumor immunity.
Trends in Patient Characteristics and COVID-19 In-Hospital Mortality in the United States During the COVID-19 Pandemic
Authors: Gregory A. Roth, Sophia Emmons-Bell, Heather M. Alger, Steven M. Bradley, Sandeep R. Das, James A. de Lemos, Emmanuela Gakidou, Mitchell S. V. Elkind, Simon Hay, Jennifer L. Hall, Catherine O. Johnson, David A. Morrow, Fatima Rodriguez, Christine Rutan, Saate Shakil, Reed Sorensen, Laura Stevens, Tracy Y. Wang, Jason Walchok, Joseph Williams, Christopher Murray
Journal: JAMA Network Open (2021)

In-hospital mortality rates from COVID-19 are high but appear to be decreasing for selected locations in the United States. It is not known whether this is because of changes in the characteristics of patients being admitted.To describe changing in-hospital mortality rates over time after accounting for individual patient characteristics.This was a retrospective cohort study of 20 736 adults with a diagnosis of COVID-19 who were included in the US American Heart Association COVID-19 Cardiovascular Disease Registry and admitted to 107 acute care hospitals in 31 states from March through November 2020. A multiple mixed-effects logistic regression was then used to estimate the odds of in-hospital death adjusted for patient age, sex, body mass index, and medical history as well as vital signs, use of supplemental oxygen, presence of pulmonary infiltrates at admission, and hospital site.In-hospital death adjusted for exposures for 4 periods in 2020.The registry included 20 736 patients hospitalized with COVID-19 from March through November 2020 (9524 women [45.9%]; mean [SD] age, 61.2 [17.9] years); 3271 patients (15.8%) died in the hospital. Mortality rates were 19.1% in March and April, 11.9% in May and June, 11.0% in July and August, and 10.8% in September through November. Compared with March and April, the adjusted odds ratios for in-hospital death were significantly lower in May and June (odds ratio, 0.66; 95% CI, 0.58-0.76; P < .001), July and August (odds ratio, 0.58; 95% CI, 0.49-0.69; P < .001), and September through November (odds ratio, 0.59; 95% CI, 0.47-0.73).In this cohort study, high rates of in-hospital COVID-19 mortality among registry patients in March and April 2020 decreased by more than one-third by June and remained near that rate through November. This difference in mortality rates between the months of March and April and later months persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity and did not appear to be associated with changes in the characteristics of patients being admitted.
Comparative Efficacy of Atezolizumab plus Bevacizumab and Other Treatment Options for Patients with Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis
Authors: Arndt Vogel, Lorenza Rimassa, Hui-Chan Sun, Ghassan K. Abou-Alfa, Anthony El-Khoueiry, David J. Pinato, Javier Sanchez Alvarez, Monica Daigl, Panos Orfanos, Michael Leibfried, Marie-Hélène Blanchet Zumofen, Vincent E. Gaillard, Philippe Merle
Journal: Liver Cancer (2021)

Most phase 3 clinical trials of systemic therapy for first-line unresectable hepatocellular carcinoma (HCC) have failed, with the exception of SHARP, REFLECT, and IMbrave150. We conducted indirect comparisons of therapies evaluated for first-line HCC treatment.We conducted a systematic review and meta-analysis of treatments for adults with locally advanced or metastatic unresectable HCC and no prior systemic treatment, including atezolizu-mab plus bevacizumab, sorafenib, lenvatinib, nivolumab, selective internal radiotherapy (SIRT), transarterial chemoembolization, and placebo or best supportive care. Randomized controlled trials published from January 1, 2007, to March 12, 2020, were retrieved from MEDLINE and Embase. Qualitative assessment of heterogeneity evaluated study designs, populations, and outcomes. Indirect comparisons used generalized linear models with random effects within a Bayesian framework and informative priors. We calculated relative efficacy estimates with 95% credible intervals (CrIs) and Bayesian posterior probability estimates of atezolizumab-bevacizumab being superior to other treatments. Nine clinical studies with a total of 3,897 participants were identified from 8,783 records and used to build the all-trials evidence network. Indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus lenvatinib (odds ratio, 0.63 [95% CrI 0.39-1.04]; with 97% Bayesian posterior probability of being superior), nivolumab (0.68 [95% CrI 0.41-1.14]; 94%), sorafenib (0.59 [95% CrI 0.39-0.87]; 99%), SIRT (0.51 [95% CrI 0.32-0.82]; 100%), or placebo/best supportive care (0.40 [95% CrI 0.25-0.64]; 100%).Within the context of indirect comparisons, analyses of OS favored atezolizumab-bevacizumab versus other treatment options for patients with locally advanced or metastatic unresectable HCC.
Abstract 16288: Comparison of Atherosclerotic Plaque Composition Among South Asians and Caucasians in the United States
Authors: Chandana Shekar, Dong Li, Lavanya Cherukuri, Kashif Shaikh, Shivani Shodhan, Negin Nezarat, Christopher Dailing, Sajad Hamal, Ferdinand Flores, Sion Roy, Alka Kanaya, Matthew Budoff
Journal: Circulation (2018)

Introduction: Studies have shown that South Asians (SA) (individuals from India, Pakistan, Bangladesh, Nepal, and Sri Lanka) living in the United States (U.S.) have a high rate of Cardiovascular Di...
Cabozantinib and dasatinib synergize to induce tumor regression in non-clear cell renal cell carcinoma
Authors: Hui-wen Lue, Daniel S. Derrick, Soumya Rao, Ahna Van Gaest, Larry Cheng, Jennifer Podolak, Samantha Lawson, Changhui Xue, Devin Garg, Ralph White, Christopher W. Ryan, Justin M. Drake, Anna Ritz, Laura M. Heiser, George V. Thomas
Journal: Cell Reports Medicine (2021)
D-DIMER TRENDS IN PATIENTS HOSPITALIZED WITH COVID-19: PATTERNS AND IN-HOSPITAL PROGNOSTIC SIGNIFICANCE
Authors: Diana Ronderos, Alaa Omar, Sayed Waqas Haider, Arsalan Rehmani, Alvaro Garcia Arenas, Kinnera Urlapu, Marin Nicu, Jonathan Bella, Sridhar Chilimuri
Journal: Journal of the American College of Cardiology (2021)
Increased risk of systemic and cardiac sarcoidosis in Black patients with cutaneous sarcoidosis
Authors: Bina Kassamali, Camila Villa-Ruiz, Kylee J.B. Kus, Daniel R. Mazori, Ali Asghar Kassamali, Olivia Gizelis, Ruth Ann Vleugels, Avery H. LaChance, Sotonye Imadojemu
Journal: Journal of the American Academy of Dermatology (2021)
LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN WORSENS TO A GREATER EXTENT POST-OPERATIVELY IN SURGICAL VERSUS PERCUTANEOUS MANAGEMENT OF SEVERE MITRAL REGURGITATION
Authors: Billy Lin, Maulin Shah, Nir Flint, Kentaro Toyama, Florian Rader, Robert Siegel
Journal: Journal of the American College of Cardiology (2021)
ROLE OF GENETICS IN SEX-SPECIFIC EFFECTS OF CLOPIDOGREL ON ATHEROTHROMBOTIC EVENTS
Authors: Amanpreet Kaur, Rachel Dreyer, Thomas W. Marsh, George Thanassoulis, Valeria Raparelli, Gail D'Onofrio, James Engert, Louise Pilote
Journal: Journal of the American College of Cardiology (2021)
Falling on One’s Sword for Truth: Deception by Ethicist Should Be Narrow
Authors: Paul J. Ford, Toni Nicoletti, Joseph P. DeMarco
Journal: The American Journal of Bioethics (2021)

"Falling on One’s Sword for Truth: Deception by Ethicist Should Be Narrow." The American Journal of Bioethics, 21(5), pp. 20–21
Deep Convolutional Neural Networks as a Diagnostic Aid—A Step Toward Minimizing Undetected Scaphoid Fractures on Initial Hand Radiographs
Authors: Jeffrey K. Jopling, Brian C. Pridgen, Serena Yeung
Journal: JAMA Network Open (2021)

Alfred P. Yoon, MD; Yi-Lun Lee, MS; Robert L. Kane, BS; Chang-Fu Kuo, MD, PhD; Chihung Lin, PhD; Kevin C. Chung, MD, MS