tbuckley/cabot-search huggingface dataset:
Isolation, characterization, and expansion of circulating tumor cells in head and neck cancers
Authors: Arutha Kulasinghe, Joanna Kapeleris, Liz Kenny, Majid Warkiani, Ian Vela, Jean Paul Thiery, Ken O’Byrne, Chamindie Punyadeera
Journal: Clinical Cancer Research (2020)

Metastasis in head and neck cancer (HNC) patients is reflected by measurable levels of circulating tumor cells (CTCs) in the blood of patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumor burden of an individual patient. Recent advancements have shown that PD-1/PD-L1 immune checkpoint therapies have durable responses in HNC. Our study was designed to use multiple CTC enrichment platforms for the capture of CTCs and novel culture formulations for the ex vivo expansion of CTCs. n=300 head and neck cancer patients were recruited to investigate the prognostic role of CTCs. We evaluated multiple CTC isolation technologies (CellSearch, filtration, CD45 depletion, inertial microfluidics) using matched patient samples, which showed that epitope-independent CTC isolation captured a greater proportion of CTCs. Molecular alterations present in the primary tissue were confirmed in the CTCs by 3D-DNA FISH (EGFR-amplification). The presence of CTC clusters was associated with the development of distant metastatic disease (P=0.0313). HNC CTC-positive patients had shorter progression-free survival (PFS) (Hazard ratio [HR]: 4.946; 95% confidence interval [CI]:1.571-15.57; P=0.0063) and PD-L1-positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011-26.33; P=0.0485). In a proof-of-principle study, we were able to demonstrate for the first time short-term patient-derived CTC cultures outside the patient’s body from 7/18 HNC samples (4/7 HPV-positive). Recently, we have preliminary data that suggest that PD-L1 is frequently expressed on CTCs in HNC and an immunoscore may be able to identify patients likely to benefit from immunotherapy—a current unmet clinical need. Expanding CTCs outside the patient’s body allows for the recapitulation of the molecular diversity present within the tumor, understanding of the disease progression, and testing of therapies.
The alternative NF-κB pathway in colorectal cancer: From genetic polymorphisms through mRNA to protein levels.
Authors: Anna G Antonacopoulou, Anastasia E Kottorou, Vasiliki Tzelepi, Fotinos-Ioannis D. Dimtrakopoulos, Thomas Makatsoris, Angelos Koutras, Haralabos Kalofonos
Journal: Journal of Clinical Oncology (2018)

e15619 Background: In colorectal cancer (CRC), there is scarce information regarding the alternative NF-κB pathway which regulates different aspects of immune functions. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples from 116 patients with CRC were analyzed with IHC to assess NF-κB2, Bcl3, RelB and NIK protein expression in tumor (T), adjacent non-neoplastic (adjNN) and non-neoplastic (NN) tissues. Gene expression was assessed with real time RT-PCR. Genotyping for BCL3 rs8100239, NFKB2 rs7897947 and rs12769316 and NIK rs7222094 was performed with High Resolution Melting Curve analysis. Results: NF-κB2 and NIK proteins were found mainly in the cytoplasm, whereas Bcl3 and RelB exhibited cytoplasmic and nuclear expression. T cells exhibited higher cytoplasmic expression of each of the four proteins compared to adjNN and NN tissue from a more distant to the tumor site (p = 0.000, for all proteins). Protein levels were variably correlated with mRNA levels. The four molecules presented similar mRNA levels between T and NN tissue except for RELB (p = 0.002). Particular protein and mRNA levels and SNPs provided prognostic value regarding PFS and OS. Patients who were rs8100239 A carriers (HR = 0.356, 95%CI: 0.148-0.862, p = 0.022) or exhibited high RELB T cytoplasmic or nuclear expression (HR = 0.276 95%CI: 0.104-0.732, p = 0.010 and HR = 0.260, 95%CI: 0.081-0.834, p = 0.023, respectively) presented with improved OS in both single and multiparametric analysis. Moreover, a longer time to progression was noted for patients who were carriers of the rs7897947 G allele (HR = 0.362 95%CI: 0.136-0.960, p = 0.041) or the rs8100239 A allele (HR = 0.292 95%CI: 0.135-0.631, p = 0.002). Similarly, patients with high T mRNA levels of each molecule under study or with high cytoplasmic T RelB (HR = 0.165 95%CI: 0.060-0.459, p = 0.001) or cytoplasmic T NIK (HR = 0.133 95%CI: 0.045-0.395, p = 0.000) or nuclear T Bcl3 expression (HR = 0.329 95%CI: 0.114-0.947, p = 0.039) had longer PFS. Conclusions: The alternative NF-κB pathway is deregulated in CRC. Selected genotypes, mRNA and protein levels of NF-κB2, Bcl3, RelB and NIK appear to have prognostic value.
Covid-19: First UK vaccine safety data are “reassuring,” says regulator
Authors: Ingrid Torjesen
Journal: BMJ (2021)

The UK's medicines regulator has described the first safety data related to covid-19 vaccines as "reassuring," with most side effects reported being mild and in line with those seen with other types of vaccine."The benefits continue to far outweigh the risks," said June Raine, chief executive of the Medicines and Healthcare Products Regulatory Agency (MHRA).The agency published yellow card data for covid-19 vaccines given between 9 December 2020 and 24 January 2021, which comprise 22 820 reports from 7 164 387 first doses and 474 156 second doses. 1 Most of the reports (16 756) are from people who received the Pfizer-BioNTech vaccine, and these list 49 472 suspected reactions.Administration of the AstraZeneca-Oxford vaccine began later, on 4 January, and 6014 yellow cards were reported up to 24 January, detailing 21 032 suspected reactions.A further 50 yellow card reports did not specify the brand of vaccine.
A novel multiple instance learning framework for COVID-19 severity assessment via data augmentation and self-supervised learning
Authors: Zekun Li, Wei Zhao, Feng Shi, Lei Qi, Xingzhi Xie, Ying Wei, Zhongxiang Ding, Yang Gao, Shangjie Wu, Jun Liu, Yinghuan Shi, Dinggang Shen
Journal: Medical Image Analysis (2021)
Trends in US Emergency Department Visits for Mental Health, Overdose, and Violence Outcomes Before and During the COVID-19 Pandemic
Authors: Kristin M. Holland, Christopher Jones, Alana M. Vivolo-Kantor, Nimi Idaikkadar, Marissa Zwald, Brooke Hoots, Ellen Yard, Ashley D’Inverno, Elizabeth Swedo, May S. Chen, Emiko Petrosky, Amy Board, Pedro Martinez, Deborah M. Stone, Royal Law, Michael A. Coletta, Jennifer Adjemian, Craig Thomas, Richard W. Puddy, Georgina Peacock, Nicole F. Dowling, Debra Houry
Journal: JAMA Psychiatry (2021)

The coronavirus disease 2019 (COVID-19) pandemic, associated mitigation measures, and social and economic impacts may affect mental health, suicidal behavior, substance use, and violence.To examine changes in US emergency department (ED) visits for mental health conditions (MHCs), suicide attempts (SAs), overdose (OD), and violence outcomes during the COVID-19 pandemic.This cross-sectional study used data from the Centers for Disease Control and Prevention's National Syndromic Surveillance Program to examine national changes in ED visits for MHCs, SAs, ODs, and violence from December 30, 2018, to October 10, 2020 (before and during the COVID-19 pandemic). The National Syndromic Surveillance Program captures approximately 70% of US ED visits from more than 3500 EDs that cover 48 states and Washington, DC.Outcome measures were MHCs, SAs, all drug ODs, opioid ODs, intimate partner violence (IPV), and suspected child abuse and neglect (SCAN) ED visit counts and rates. Weekly ED visit counts and rates were computed overall and stratified by sex.From December 30, 2018, to October 10, 2020, a total of 187 508 065 total ED visits (53.6% female and 46.1% male) were captured; 6 018 318 included at least 1 study outcome (visits not mutually exclusive). Total ED visit volume decreased after COVID-19 mitigation measures were implemented in the US beginning on March 16, 2020. Weekly ED visit counts for all 6 outcomes decreased between March 8 and 28, 2020 (March 8: MHCs = 42 903, SAs = 5212, all ODs = 14 543, opioid ODs = 4752, IPV = 444, and SCAN = 1090; March 28: MHCs = 17 574, SAs = 4241, all ODs = 12 399, opioid ODs = 4306, IPV = 347, and SCAN = 487). Conversely, ED visit rates increased beginning the week of March 22 to 28, 2020. When the median ED visit counts between March 15 and October 10, 2020, were compared with the same period in 2019, the 2020 counts were significantly higher for SAs (n = 4940 vs 4656, P = .02), all ODs (n = 15 604 vs 13 371, P < .001), and opioid ODs (n = 5502 vs 4168, P < .001); counts were significantly lower for IPV ED visits (n = 442 vs 484, P < .001) and SCAN ED visits (n = 884 vs 1038, P < .001). Median rates during the same period were significantly higher in 2020 compared with 2019 for all outcomes except IPV.These findings suggest that ED care seeking shifts during a pandemic, underscoring the need to integrate mental health, substance use, and violence screening and prevention services into response activities during public health crises.
Severe respiratory syncytial virus disease in preterm infants: a case of innate immaturity
Authors: Jeremy Anderson, Lien Anh Ha Do, Danielle Wurzel, Zheng Quan Toh, Kim Mulholland, Daniel G Pellicci, Paul V Licciardi
Journal: Thorax (2021)

Respiratory syncytial virus (RSV) is the most common viral pathogen associated with acute lower respiratory tract infection (LRTI) in children under 5 years of age. Severe RSV disease is associated with the development of chronic respiratory complications such as recurrent wheezing and asthma. A common risk factor for developing severe RSV disease is premature gestation and this is largely due to an immature innate immune system. This increases susceptibility to RSV since the innate immune system is less able to protect against pathogens at a time when adaptive immunity has not fully developed. This review focuses on comparing different aspects of innate immunity between preterm and term infants to better understand why preterm infants are more susceptible to severe RSV disease. Identifying early life innate immune biomarkers associated with the development of severe RSV disease, and understanding how these compare between preterm and term infants, remains a critically important question that would aid the development of interventions to reduce the burden of disease in this vulnerable population.
Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality
Authors: William R. Morgenlander, Stephanie N. Henson, Daniel R. Monaco, Athena Chen, Kirsten Littlefield, Evan M. Bloch, Eric Fujimura, Ingo Ruczinski, Andrew R. Crowley, Harini Natarajan, Savannah E. Butler, Joshua A. Weiner, Mamie Z. Li, Tania S. Bonny, Sarah E. Benner, Ashwin Balagopal, David Sullivan, Shmuel Shoham, Thomas C. Quinn, Susan H. Eshleman, Arturo Casadevall, Andrew D. Redd, Oliver Laeyendecker, Margaret E. Ackerman, Andrew Pekosz, Stephen J. Elledge, Matthew Robinson, Aaron A.R. Tobian, H. Benjamin Larman
Journal: Journal of Clinical Investigation (2021)

SARS-CoV-2 (CoV2) antibody therapies, including COVID-19 convalescent plasma (CCP), monoclonal antibodies, and hyperimmune globulin, are among the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the 4 endemic human coronavirus (HCoV) genomes in 126 CCP donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies against CoV2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a 2-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting desired therapeutics and understanding the complex immune responses elicited by CoV2 infection.
CMTM6 and PD-L1 coexpression is associated with an active immune microenvironment and a favorable prognosis in colorectal cancer
Authors: Qi-Hua Peng, Chun-Hua Wang, Hong-Min Chen, Rong-Xin Zhang, Zhi-Zhong Pan, Zhen-Hai Lu, Gao-Yuan Wang, Xin Yue, Wenlin Huang, Ran-Yi Liu
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), a programmed death-ligand 1 (PD-L1) regulator, is widely expressed in various tumors and regulates the immune microenvironment. However, its prognostic value remains controversial, and the roles of CMTM6 in colorectal cancer (CRC) are still unknown. In this study, we aimed to elaborate the expression patterns of CMTM6 and PD-L1 in CRC and investigate their relationship with the infiltration of T cells and the prognosis of patients with CRC. Methods Analysis of CMTM6 mRNA levels, gene ontology enrichment analysis and single-sample gene set enrichment analysis were performed in a The Cancer Genome Atlas colon cancer cohort. The expression of CMTM6 and PD-L1 and the infiltration of T cells in tumor tissues from our cohort containing 156 patients with CRC receiving adjuvant chemotherapy and 77 patients with CRC without chemotherapy were examined by immunohistochemistry assay. Results CMTM6 expression was upregulated in CRC compared with normal colon tissues, and CMTM6 levels were lower in advanced tumors than in early-stage tumors. High expression of CMTM6 correlated with lower pT stage and more CD4 + /CD8 + tumor-infiltrating lymphocytes (TILs) and predicted a favorable prognosis in CRC. PD-L1 was expressed in CRC tissues at a low level, and PD-L1 positivity in tumor stroma (PD-L1(TS)), but not PD-L1 positivity in cancer cells (PD-L1(CC)), was associated with an increased density of CD4 + TILs and a favorable prognosis. The coexpression status of CMTM6 and PD-L1(TS) divided patients with CRC into three groups with low, moderate and high risks of progression and death, and patients with CMTM6 High /PD-L1(TS) + status had the longest survival. Moreover, the prognostic value of CMTM6/PD-L1 expression was more significant in patients with CRC treated with adjuvant chemotherapy than in those not treated with chemotherapy. Conclusion CMTM6 has a critical impact on the immune microenvironment and can be used as an independent prognostic factor for CRC. The coexpression status of CMTM6 and PD-L1 can be used as a new classification to stratify the risk of progression and death for patients with CRC, especially for patients receiving adjuvant chemotherapy. These findings may provide insights into improving responses to immunotherapy-included comprehensive treatment for CRC in the future.
Screening for upper gastrointestinal cancers with magnetically controlled capsule gastroscopy: a feasibility study
Authors: Zhen Li, Jing Liu, Chao-Ran Ji, Fei-Xue Chen, Fu-Guo Liu, Jian Ge, Yong Chen, Xue-Guo Sun, Yan-Yan Lu, Gui-Hua Cheng, Jie Zhang, Peng Li, Ji-Yong Liu, Chong-Mei Yang, Xiu-Li Zuo, Yan-Qing Li
Journal: Endoscopy (2021)

Abstract Background The medical consortium is an intensive and disease-specific association that integrates tertiary public hospitals and medical examination centers in China. We aimed to evaluate the feasibility of the medical consortium for screening upper gastrointestinal (GI) cancers (MCSC) by magnetically controlled capsule gastroscopy (MCCG). Methods 6627 asymptomatic subjects underwent MCCG as part of health check-ups in the MCSC between March and November 2018. Relevant clinical data were collected and analyzed. Results The MCSC detected 32 patients with upper GI cancer (0.48 %) confirmed by pathology. The detection rate of early gastric cancer was 16.67 % (4 /24). Gastric polyps, ulcers, and submucosal tumors were found in 15.54 %, 3.76 %, and 3.17 % of subjects, respectively. The whole GI preparation and operation process were well tolerated. Conclusions The MCSC was a feasible model for upper GI cancer screening, especially for asymptomatic subjects. Further prospective studies with better operational quality control are warranted.
Evaluating the Safety of Cannabinoid-Based Medicines for Older Adults
Authors: Donna M. Fick
Journal: JAMA Network Open (2021)

Should cannabinoid-based medicines (CBMs) be avoided for older adults?Velayudhan and colleagues 1 examine whether the use of CBMs containing delta-9-tetrahydrocannabinol (THC) increases the risk of neuropsychiatric adverse events (AEs) in adults aged 50 years and older.As the authors note, 1 it is already known that regular use of cannabis with high levels of THC is associated with increased psychotic symptoms in younger persons with established psychotic disorders, but little is known about AEs associated with the use of THC-containing CBMs in older adults, who increasingly use CBMs to manage chronic pain and other health conditions. 2Velayudhan and colleagues 1 performed a rigorous systematic review of randomized clinical trials (RCTs) published from 1990 to October 2020 that examined the safety and tolerability of different CBMs.The authors examined 30 RCTs using THC-only CBMs (total THC exposure, 1252.83person-years) and 24 RCTs using CBMs with different combinations of cannabidiol (CBD) and THC
High Expression of FGF2/SDC1 Signaling Contributes to Poor Clinical Outcome in Hodgkin Lymphoma Patients and SDC1 siRNA Suppresses Proliferation, Migration, and Invasion in Hodgkin Lymphoma Cells
Authors: Poonam Nagpal, Andre Goy, Anju Gangadharan, Mohamed R. Akl, Ivan Voznenko, Mihir Soni, Betty Tai, Tasheka Cousins, Tatyana A Feldman, Sathyen A. Prabhu, Amanda Ally, Morgan Anderson-Crannage, Lori A. Leslie, K Lady, Fareeha Kanwal, Tatsunari Tomiyama, Aliya Khurram, Catherine M. Capac, Matthew Gliksman, Despina Helios, Dante B. Descalzi-Montoya, Andrew L. Pecora, K. Stephen Suh
Journal: Blood (2017)
Feasibility and Safety of Tethered Capsule Endomicroscopy in Patients With Barrett’s Esophagus in a Multi-Center Study
Authors: Jing Dong, Catriona Grant, Barry Vuong, Norman Nishioka, Anna Huizi Gao, Matthew Beatty, Grace Baldwin, Aaron Baillargeon, Ara Bablouzian, Patricia Grahmann, Nitasha Bhat, Emily Ryan, Amilcar Barrios, Sarah Giddings, Timothy Ford, Emilie Beaulieu-Ouellet, Seyed Hamid Hosseiny, Irene Lerman, Wolfgang Trasischker, Rohith Reddy, Kanwarpal Singh, Michalina Gora, Daryl Hyun, Lucille Quénéhervé, Michael Wallace, Herbert Wolfsen, Prateek Sharma, Kenneth K. Wang, Cadman L. Leggett, John Poneros, Julian A. Abrams, Charles Lightdale, Samantha Leeds, Mireille Rosenberg, Guillermo J. Tearney
Journal: Clinical Gastroenterology and Hepatology (2021)
Abstract 14747: Dwindling Trends of Cardiology Admissions Amidst Covid-19 Pandemic in a Tertiary Care Center of Pakistan
Authors: Jamshed Ali, Osman Faheem, Pirbhat Shams, ghufran adnan, Maria Khan
Journal: Circulation (2020)

Introduction: Social containment measures have been adopted globally to control COVID-19 outbreak. Reduction in hospital visits and inpatient admission rates have become cause for concern. Through this study we aimed to analyze the impact of SARS-CoV-2 virus Outbreak on cardiology inpatient admissions at a tertiary care hospital in Pakistan. Hypothesis: COVID-19 pandemic has resulted in significant decline in cardiology admissions. Methods: We conducted a retrospective study at our center. Admission log was accessed via electronic record system. Comparison was made for same months of 2019 and 2020 with regard to cardiology inpatient admissions. Results: A total of 239 patients were admitted to cardiology services in 2019 period and 106 in 2020 period with resultant reduction of 55.6%. Number of patients admitted to the coronary care unit were 179 and 78 respectively where as the numbers declined to 28 from 60 for cardiac step down. Reduction for admission numbered to 52.4% for males and 38.89% for females. 9.3% patients left against medical advice in 2019 and 3.4% in 2020. Conclusions: Our study concludes that numbers of cardiology admissions have dwindled. Possible explanation for this can be implementation of social containment and fear of acquiring infection. This has raised a question of whether a significant number of cardiovascular morbidity and mortality has occurred without seeking medical attention and has went unrecorded during the pandemic. This calls for stringent diagnostic measures in future to diagnose previously unrecorded burden.
National Trends in Heart Failure Hospitalizations and Readmissions From 2010 to 2017
Authors: Manyoo A. Agarwal, Gregg C. Fonarow, Boback Ziaeian
Journal: JAMA Cardiology (2021)

Previous studies have described the secular trends of overall heart failure (HF) hospitalizations, but the literature describing the national trends of unique index hospitalizations and readmission visits for the primary management of HF is lacking.To examine contemporary overall and sex-specific trends of unique primary HF (grouped by number of visits for the same patient in a given year) and 30-day readmission visits in a large national US administrative database from 2010 to 2017.This cohort study used data from all adult hospitalizations in the Nationwide Readmission Database from January 1, 2010, to December 31, 2017, with a primary diagnosis of HF. Data analyses were conducted from March to November 2020.Admission for a primary diagnosis of HF at discharge.Unique and overall hospitalizations with a primary diagnosis of HF and postdischarge readmissions. Unique primary HF hospitalizations were grouped by number of visits for the same patient in a given year.There were 8 273 270 primary HF hospitalizations with a single primary HF admission present in 5 092 626 unique patients, and 1 269 109 had 2 or more HF hospitalizations. The mean age was 72.1 (95% CI, 72.0-72.3) years, and 48.9% (95% CI, 48.7-49.0) were women. The primary HF hospitalization rates per 1000 US adults declined from 4.4 in 2010 to 4.1 in 2013 and then increased from 4.2 in 2014 to 4.9 in 2017. The rates per 1000 US adults for postdischarge HF readmissions (1.0 in 2010 to 0.9 in 2014 to 1.1 in 2017) and all-cause 30-day readmissions (0.8 in 2010 to 0.7 in 2014 to 0.9 in 2017) had similar trends.In this analysis of a nationally representative administrative data set, for primary HF admissions, crude rates of overall and unique patient hospitalizations declined from 2010 to 2014 followed by an increase from 2014 to 2017. Additionally, readmission visits after index HF hospitalizations followed a similar trend. Future studies are needed to verify these findings to improve policies for HF management.