tbuckley/cabot-search huggingface dataset:
Lost in translation: true clinical impact of reflectance confocal microscopy overlooked in ‘Biopsy outperforms reflectance confocal microscopy in diagnosing and subtyping basal cell carcinoma: results and experiences from a randomized controlled multicentre trial’
Authors: M. Gill, G. Pellacani, J.M. Grant‐Kels, M. Ardigò, C.‐S.J. Chen, S. Gonzalez, P. Guitera, C. Longo, J. Malvehy, O. Markowitz, S. Puig, H. Rabinovitz, B.K. Rao, A. Scope, M. Ulrich
Journal: British Journal of Dermatology (2020)

Linked Article: Woliner‐van der Weg et al. Br J Dermatol 2021; 184:663–671.
Safety and Efficacy of Vorinostat Plus Sirolimus or Everolimus in Patients with Relapsed Refractory Hodgkin Lymphoma
Authors: Filip Janku, Haeseong Park, S. Greg Call, Kiran Madwani, Yasuhiro Oki, Vivek Subbiah, David S. Hong, Aung Naing, Vivianne M. Velez-Bravo, Tamara G. Barnes, Fredrick B. Hagemeister, Gerald S. Falchook, Daniel D. Karp, Jennifer J. Wheler, Sarina A. Piha-Paul, Ignacio Garrido-Laguna, Elizabeth J. Shpall, Luis E. Fayad, Sattva S. Neelapu, Funda Meric-Bernstam, Razelle Kurzrock, Michelle A. Fanale
Journal: Clinical Cancer Research (2020)

Preclinical and early clinical data suggested that combining histone deacetylase (HDAC) and mTOR inhibitors can synergistically inhibit Hodgkin lymphoma.During the dose-escalation study (ClinicalTrials.gov number: NCT01087554) with the HDAC inhibitor vorinostat and the mTOR inhibitor sirolimus (V+S), a patient with Hodgkin lymphoma refractory to nine prior therapies demonstrated a partial response (PR) lasting for 18.5 months, which promoted additional enrollment of patients with Hodgkin lymphoma as well as exploration of an alternative combination of vorinostat and mTOR inhibitor everolimus (V+E).A total of 40 patients with refractory Hodgkin lymphoma received V+S (n = 22) or V+E (n = 18). Patients received a median of five prior therapies, including brentuximab (n = 39), autologous stem cell transplantation (n = 26), and allogeneic stem cell transplantation (n = 12). The most frequent grade ≥3 treatment-related adverse event was thrombocytopenia in 55% and 67% of patients treated with V+S and V+E, respectively. Complete response was reported in 6 (27%) patients treated with V+S and 2 (11%) patients treated with V+E, and PR was reported in 6 patients (27%) treated with V+S and 4 (22%) patients treated with V+E (objective response rate of 55% and 33%, respectively). In summary, combined HDAC and mTOR inhibition had encouraging activity in heavily pretreated patients with relapsed/refractory Hodgkin lymphoma and warrants further investigation.Combined HDAC and mTOR inhibition has salutary activity in patients with relapsed refractory Hodgkin lymphoma and warrants further investigation.
Accuracy of point-of-care diagnostic tests for SARS-CoV-2 antibodies (IgM/IgG) is heterogeneous
Authors: Henry S. Sacks
Journal: Annals of Internal Medicine (2020)

Source CitationRiccò M, Ferraro P, Gualerzi G, et al. Point-of-care diagnostic tests for detecting SARS-CoV-2 antibodies: a systematic review and meta-analysis of real-world data. J Clin Med. 2020;9:1515. https://pubmed.ncbi.nlm.nih.gov/32443459/AbstractClinical Impact RatingsGIM/FP/GP: Emergency Med: Hospitalists: Infectious Disease: Public Health:
Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions
Authors: Jules Russick, Pierre-Emmanuel Joubert, Mélanie Gillard-Bocquet, Carine Torset, Maxime Meylan, Florent Petitprez, Marie-Agnes Dragon-Durey, Solenne Marmier, Aditi Varthaman, Nathalie Josseaume, Claire Germain, Jérémy Goc, Marie-Caroline Dieu-Nosjean, Pierre Validire, Ludovic Fournel, Laurence Zitvogel, Gabriela Bindea, Audrey Lupo, Diane Damotte, Marco Alifano, Isabelle Cremer
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Natural killer (NK) cells play a crucial role in tumor immunosurveillance through their cytotoxic effector functions and their capacity to interact with other immune cells to build a coordinated antitumor immune response. Emerging data reveal NK cell dysfunction within the tumor microenvironment (TME) through checkpoint inhibitory molecules associated with a regulatory phenotype. Objective We aimed at analyzing the gene expression profile of intratumoral NK cells compared with non-tumorous NK cells, and to characterize their inhibitory function in the TME. Methods NK cells were sorted from human lung tumor tissue and compared with non- tumoral distant lungs. Results In the current study, we identify a unique gene signature of NK cell dysfunction in human non-small cell lung carcinoma (NSCLC). First, transcriptomic analysis reveals significant changes related to migratory pattern with a downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) and CX3C chemokine receptor 1 (CX3CR1) and overexpression of C-X-C chemokine receptor type 5 (CXCR5) and C-X-C chemokine receptor type 6 (CXCR6). Second, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and killer cell lectin like receptor (KLRC1) inhibitory molecules were increased in intratumoral NK cells, and CTLA-4 blockade could partially restore MHC class II level on dendritic cell (DC) that was impaired during the DCs/NK cell cross talk. Finally, NK cell density impacts the positive prognostic value of CD8 + T cells in NSCLC. Conclusions These findings demonstrate novel molecular cues associated with NK cell inhibitory functions in NSCLC.
Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival
Authors: Aude Chiot, Sakina Zaïdi, Charlène Iltis, Matthieu Ribon, Félix Berriat, Lorenzo Schiaffino, Ariane Jolly, Pierre de la Grange, Michel Mallat, Delphine Bohl, Stéphanie Millecamps, Danielle Seilhean, Christian S. Lobsiger, Séverine Boillée
Journal: Nature Neuroscience (2020)
Thyroid Metastasis From Cutaneous Melanoma on an 18F-FDG PET/CT Study
Authors: Ignacio León-Asuero-Moreno, Francisco Javier García-Gómez, Juan José Ríos-Martín, María del Carmen Álamo-de-la-Gala, María Cinta Calvo-Morón
Journal: Clinical Nuclear Medicine (2020)

The thyroid gland is an uncommon location for metastasis. We report a 59-year-old woman with a history of cutaneous malignant melanoma. A unique hypermetabolic mass on the left thyroid lobe was identified by control F-FDG PET/CT scan, leading to dysphagia and stridor clinic. Total thyroidectomy and lymphadenectomy were performed with histopathological results concordant with metastasis from melanoma. Despite its rarity, finding focal thyroid lesions in patients with an oncological history should alert us, recommending that its metastatic etiology be ruled out.
65P Association of SNPs at 10q21-25 chromosome in patients with colorectal cancer in the Kazakhstan population
Authors: S. Kolesnichenko, I. Kadyrova, D. Babenko, Y. Kolesnikova, L. Akhmaltdinova, A. Turmukhambetova, V. Sirota, V. Zhumalieva
Journal: Annals of Oncology (2020)
Eomes-Dependent Loss of the Co-activating Receptor CD226 Restrains CD8+ T Cell Anti-tumor Functions and Limits the Efficacy of Cancer Immunotherapy
Authors: Marianne Weulersse, Assia Asrir, Andrea C. Pichler, Lea Lemaitre, Matthias Braun, Nadège Carrié, Marie-Véronique Joubert, Marie Le Moine, Laura Do Souto, Guillaume Gaud, Indrajit Das, Elisa Brauns, Clara M. Scarlata, Elena Morandi, Ashmitha Sundarrajan, Marine Cuisinier, Laure Buisson, Sabrina Maheo, Sahar Kassem, Arantxa Agesta, Michaël Pérès, Els Verhoeyen, Alejandra Martinez, Julien Mazieres, Loïc Dupré, Thomas Gossye, Vera Pancaldi, Camille Guillerey, Maha Ayyoub, Anne S. Dejean, Abdelhadi Saoudi, Stanislas Goriely, Hervé Avet-Loiseau, Tobias Bald, Mark J. Smyth, Ludovic Martinet
Journal: Immunity (2020)
Scientific Ambiguity in the Time of Coronavirus Disease 2019
Authors: Pedro de la Oliva, Miguel Rodriguez-Rubio, Julio García-Rodríguez
Journal: JAMA Pediatrics (2020)

Alfredo Tagarro, PhD, MD; Cristina Epalza, PhD, MD; Mar Santos, PhD, MD; Francisco José Sanz-Santaeufemia, PhD, MD; Enrique Otheo, PhD, MD; Cinta Moraleda, PhD, MD; Cristina Calvo, PhD, MD
Modernising case finding for α1-antitrypsin deficiency by DNA sequencing of COPD patients
Authors: Mark Quinn, Alice M. Turner
Journal: European Respiratory Journal (2020)

Alpha-1-antitrypsin deficiency (AATD) is a hereditary metabolic disorder caused by mutations in the SERPINA1 gene that result in a reduction in the serum concentration of the protein alpha-1-antitrypsin (AAT), and a predisposition to COPD [1]. AAT functions as an inhibitor of neutrophil elastase (and other proteases) and is essential in maintaining a balance of protease and antiprotease activity in the lungs [2]. Imbalance causes an escalating cycle of inflammation and degradation of lung tissue that, over time, leads to COPD [3]. Commenting on the use of DNA sequencing in helping to reduce the reported under-diagnosing of alpha-1-antitrypsin deficiency <https://bit.ly/2ZPZbjx>
Characterization of the intestinal microbiota during <i>Citrobacter rodentium</i> infection in a mouse model of infection-triggered Parkinson’s disease
Authors: Tyler Cannon, Anshul Sinha, Louis-Eric Trudeau, Corinne F. Maurice, Samantha Gruenheid
Journal: Gut Microbes (2020)

Parkinson's disease (PD) is a neurodegenerative disorder that has been shown to be influenced by the intestinal milieu. The gut microbiota is altered in PD patients, and murine studies have begun suggesting a causative role for the gut microbiota in progression of PD. We have previously shown that repeated infection with the intestinal murine pathogen Citrobacter rodentium resulted in the development of PD-like pathology in Pink1−/- mice compared to wild-type littermates. This addendum aims to expand this work by characterizing the gut microbiota during C. rodentium infection in our Pink1−/- PD model. We observed little disturbance to the fecal microbiota diversity both between infection timepoints and between Pink1−/- and wild-type control littermates. However, the level of short-chain fatty acids appeared to be altered over the course of infection with butyric acid significantly increasing in Pink1−/- mice and isobutyric acid increasing in wild-type mice.
Injury incidence and characteristics for elite, male, artistic USA gymnastics competitions from 2008 to 2018
Authors: David William Kruse, Andrew Seiji Nobe, John Billimek
Journal: British Journal of Sports Medicine (2020)

Objectives To determine the injury incidence and characteristics for elite, male, artistic USA gymnasts during gymnastics competitions, held in the USA, from 2008 to 2018. Methods Injury documentation performed by lead physician and certified athletic trainers at elite junior and senior USA Gymnastics competitions from 2008 to 2018 were reviewed and compiled into an excel database. Injury incidence was computed per 1000 registered gymnasts by competition setting as well as injury location, type, cause, severity, and setting. Results From 2008 to 2018, 180 injuries were reported in a total of 2102 gymnasts with injury incidence of 85.6 per 1000 gymnasts (95% CI 73.4 to 97.8). The most common injury site was at the ankle (16.7 per 1000 gymnasts, 95% CI 10.9 to 22.4), and muscle strain/rupture/tear was the most common type of injury (28.5 per 1000 gymnasts, 95% CI 21.2 to 35.9). The most common cause was contact with surface (56.1 per 1000 gymnasts, 95% CI 46.1 to 66.2), and the event where most injuries were sustained was the vault (21.9 per 1000 gymnasts, 95% CI 15.4 to 28.4). Incidence of time loss injuries was 38.5 per 1000 gymnasts (95% CI 30.1 to 47.0). Injury incidence was higher during competition (58.5 per 1000 gymnasts, 95% CI 48.2 to 68.8) than during training (27.1 per 1000 RG, 95% CI 19.9 to 34.3; RR 2.16, 95% CI 1.59 to 2.94, p&lt;0.001); injury incidence was greater at Olympic Trials (RR 3.23, 95% CI 1.24 to 8.47, p=0.017) than at National Qualifier meets. We report concussion incidence in gymnastics (5.7 per 1000 gymnasts, 95% CI 2.3 to 9.2). Conclusions This is the largest injury study to date for male artistic gymnasts (180 injuries, 2102 gymnasts, 11 years).
Association of asthma severity and educational attainment at age 6–7 years in a birth cohort: population-based record-linkage study
Authors: Annette Evans, Daniel Farewell, Joanne Demmler, Amrita Bandyopadhyay, Colin Victor Eric Powell, Shantini Paranjothy
Journal: Thorax (2020)

Background There is conflicting research about the association between asthma and poor educational attainment that may be due to asthma definitions. Our study creates seven categories of current chronic and acute asthma to investigate if there is an association for poorer educational attainment at age 6–7 years, and the role of respiratory infections and school absence. Methods This study used a population-based electronic cross-sectional birth cohort 1998–2005, in Wales, UK, using health and education administrative datasets. Current asthma or wheeze categories were developed using clinical management guidelines in general practice (GP) data, acute asthma was inpatient hospital admissions and respiratory infections were the count of GP visits, from birth to age 6–7 years. We used multilevel logistic regression grouped by schools to ascertain if asthma or wheeze was associated with not attaining the expected level in teacher assessment at Key Stage 1 (KS1) adjusting for sociodemographics, perinatal, other respiratory illness and school characteristics. We tested if absence from school was a mediator in this relationship using the difference method. Results There were 85 906 children in this population representative cohort with 7-year follow-up. In adjusted multilevel logistic regression, only asthma inpatient hospital admission was associated with increased risk for not attaining the expected level at KS1 (adjusted OR 1.14 95% CI (1.02 to 1.27)). Lower respiratory tract infection (LRTI) GP contacts remained an independent predictor for not attaining the expected level of education. Absence from school was a potential mediator of the association between hospital admission and educational attainment. Conclusions Clinicians and educators need to be aware that children who have inpatient hospital admissions for asthma or wheeze, or repeated LRTI, may require additional educational support for their educational outcomes.
The Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of acute leukemia
Authors: Michael M Boyiadzis, Ivan Aksentijevich, Daniel A Arber, John Barrett, Renier J Brentjens, Jill Brufsky, Jorge Cortes, Marcos De Lima, Stephen J Forman, Ephraim J Fuchs, Linda J Fukas, Steven D Gore, Mark R Litzow, Jeffrey S Miller, John M Pagel, Edmund K Waller, Martin S Tallman
Journal: Journal for ImmunoTherapy of Cancer (2020)

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment of patients with acute leukemia. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop a clinical practice guideline composed of consensus recommendations on immunotherapy for the treatment of acute lymphoblastic leukemia and acute myeloid leukemia.
39P TGF-β1 and TNF-α: Antagonistic cytokines controlling extracellular matrix remodeling after radioactive iodine therapy for papillary thyroid carcinoma
Authors: A.E. Stanciu, A.E. Hurduc, M.M. Stanciu, M. Bolovan, A. Zamfirescu
Journal: Annals of Oncology (2020)
Delivering transformative action in paediatric pain: a Lancet Child &amp; Adolescent Health Commission
Authors: Christopher Eccleston, Emma Fisher, Richard F Howard, Rebeccah Slater, Paula Forgeron, Tonya M Palermo, Kathryn A Birnie, Brian J Anderson, Christine T Chambers, Geert Crombez, Gustaf Ljungman, Isabel Jordan, Zachary Jordan, Caitriona Roberts, Neil Schechter, Christine B Sieberg, Dick Tibboel, Suellen M Walker, Dominic Wilkinson, Chantal Wood
Journal: The Lancet Child & Adolescent Health (2020)
FRI0049 Efficacy of leflunomide in rheumatoid arthritis patients refractory to multiple dmards
Authors: IM Laurindo, CT Borges, JA Kochen, DY Torigoe
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Ineffective control of clinical activity is frequently observed in a subgroup of rheumatoid arthritis (RA) patients that present severe evolution with no response to classical DMARDs isolated or in association. <h3>Objectives</h3> To assess the efficacy of leflunomide in difficult RA in a 24-week open-label prospective study. <h3>Methods</h3> 20 patients fulfilling ACR diagnosis criteria were selected based on non-response or adverse effects to at least three DMARDS (including methotrexate -MTX). The patients were regularly attending the outpatient clinic for at least 5 years and this study did not bring alterations in their routine care and follow-up. All patients were female, with erosive disease and in clinical activity: mean DAS (disease activity score) = 5.30. Their mean age was 46 years (range 32 to 61) and the mean RA duration was 12 years (range 5 to 27), and FR positive in 19, previous use of at least 3 DMARDs (mean 4; maximum 7). At the beginning of the study chloroquine was currently given to 8 patients, MTX to 13 (mean dose = 19 mg/week; range15–25) and sulfasalazine to 12. Seven patients were receiving azathioprine and only one was on methilprednisolone monthly pulses. All subjects were receiving oral corticosteroids (CE) (mean 10,5 mg/day; range 7,5 to 20 mg) and NSAIDs. While oral dose CE and NSAIDS were maintained, all DMARDS were suspended and Leflunomide administered at the initial dose of 100 mg/day/3 days followed by 20 mg/day, with no washout period. Clinical exams and laboratory tests were performed monthly. <h3>Results</h3> After 6 months, 60% of the patients were considered responders achieving ACR &gt;or = 20%. Regarding DAS 28, 75% of the patients were considered responders. CE oral dose was reduced in 7 patients. Adverse effects were observed in 4 patients: diarrhoea in 2; alopecia in 2. Lymphopenia was observed in one patient who was well controlled (ACR50 response) with leflunomide every other day. Only one patient suspended treatment (alopecia plus clinical activity). There was no increase in transaminase enzymes levels. Increase in alkalyne phosphatase levels was observed in 5 patients: in four, increase was mild (&lt; 2 times that of normal range) and in only one &gt; or = 2 times that of normal range. <h3>Conclusion</h3> Patients refractory to multiple DMARDS can safely achieve a favourable response with leflunomide.
A retrospective comparison of CD19 single and CD19/CD22 bispecific targeted chimeric antigen receptor T cell therapy in patients with relapsed/refractory acute lymphoblastic leukemia
Authors: Yiyun Wang, Yingying Yang, Ruimin Hong, Houli Zhao, Guoqing Wei, Wenjun Wu, Huijun Xu, Jiazhen Cui, Yanlei Zhang, Alex H. Chang, Yongxian Hu, He Huang
Journal: Blood Cancer Journal (2020)
Prostate Cancer Incidence and Survival, by Stage and Race/Ethnicity — United States, 2001–2017
Authors: David A. Siegel, Mary Elizabeth O’Neil, Thomas B. Richards, Nicole F. Dowling, Hannah K. Weir
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Among U.S. men, prostate cancer is the second leading cause of cancer-related death (1). Past studies documented decreasing incidence of prostate cancer overall since 2000 but increasing incidence of distant stage prostate cancer (i.e., signifying spread to parts of the body remote from the primary tumor) starting in 2010 (2,3). Past studies described disparities in prostate cancer survival by stage, age, and race/ethnicity using data covering ≤80% of the U.S. population (4,5). To provide recent data on incidence and survival of prostate cancer in the United States, CDC analyzed data from population-based cancer registries that contribute to U.S. Cancer Statistics (USCS).* Among 3.1 million new cases of prostate cancer recorded during 2003-2017, localized, regional, distant, and unknown stage prostate cancer accounted for 77%, 11%, 5%, and 7% of cases, respectively, but the incidence of distant stage prostate cancer significantly increased during 2010-2017. During 2001-2016, 10-year relative survival for localized stage prostate cancer was 100%. Overall, 5-year survival for distant stage prostate cancer improved from 28.7% during 2001-2005 to 32.3% during 2011-2016; for the period 2001-2016, 5-year survival was highest among Asian/Pacific Islanders (API) (42.0%), followed by Hispanics (37.2%), American Indian/Alaska Natives (AI/AN) (32.2%), Black men (31.6%), and White men (29.1%). Understanding incidence and survival differences by stage, race/ethnicity, and age can guide public health planning related to screening, treatment, and survivor care. Future research into differences by stage, race/ethnicity, and age could inform interventions aimed at improving disparities in outcomes.
NAFLD-related mortality: simple hepatic steatosis is not as ‘benign’ as thought
Authors: Herbert Tilg, Giovanni Targher
Journal: Gut (2020)

‘ Is life worth living? It all depends on the liver’ (American philosopher William James [1842—1910])

Non-alcoholic fatty liver disease (NAFLD) is currently the most frequent global liver disease.1 Disease presentation includes various clinical phenotypes ranging from simple steatosis (non-alcoholic fatty liver to non-alcoholic steatohepatitis (NASH), fibrosis without inflammation, cirrhosis and hepatocellular carcinoma. In the majority of NAFLD patients, liver histology is characterised by simple steatosis, whereas up to 30% of patients exhibits liver inflammation ± fibrosis. Several cohort studies have suggested that NAFLD-related mortality is mainly due to cardiovascular diseases, extrahepatic cancers and liver-related complications. Furthermore, whereas prognosis of simple steatosis is generally considered rather ‘benign’, various studies from the past years have supported the notion that not necroinflammation but stage of fibrosis drives long-term prognosis and mortality.2 3 A recent meta-analysis of 13 studies (including a total of 4428 patients) reported that NAFLD-related fibrosis correlated with risk of mortality and liver-related morbidity.4 Stage of fibrosis was highly predictive for all-cause mortality, whereas NASH and simple steatosis were not prognostically relevant.4 Bridging fibrosis as suggested from another multicentre study was associated predominantly with extrahepatic cancers.5 A recent study from the USA showed that NAFLD contributed to ~10% of all-cause mortality and >30% of liver disease-related and diabetes-related deaths, thus further supporting that NAFLD-related mortality is highly relevant. …
Nanoengineered shear-thinning and bioprintable hydrogel as a versatile platform for biomedical applications
Authors: Nooshin Zandi, Ehsan Shirzaei Sani, Ebrahim Mostafavi, Dina M. Ibrahim, Bahram Saleh, Mohammad Ali Shokrgozar, Elnaz Tamjid, Paul S. Weiss, Abdolreza Simchi, Nasim Annabi
Journal: Biomaterials (2020)
Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC
Authors: Mark M. Awad, Shirish M. Gadgeel, Hossein Borghaei, Amita Patnaik, James Chih-Hsin Yang, Steven F. Powell, Ryan D. Gentzler, Renato G. Martins, James P. Stevenson, Mehmet Altan, Shadia I. Jalal, Amit Panwalkar, Matthew Gubens, Lecia V. Sequist, Sanatan Saraf, Bin Zhao, Bilal Piperdi, Corey J. Langer
Journal: Journal of Thoracic Oncology (2020)