tbuckley/cabot-search huggingface dataset:
Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma
Authors: Livnat Jerby-Arnon, Cyril Neftel, Marni E. Shore, Hannah R. Weisman, Nathan D. Mathewson, Matthew J. McBride, Brian Haas, Benjamin Izar, Angela Volorio, Gaylor Boulay, Luisa Cironi, Alyssa R. Richman, Liliane C. Broye, Joseph M. Gurski, Christina C. Luo, Ravindra Mylvaganam, Lan Nguyen, Shaolin Mei, Johannes C. Melms, Christophe Georgescu, Ofir Cohen, Jorge E. Buendia-Buendia, Asa Segerstolpe, Malika Sud, Michael S. Cuoco, Danny Labes, Simon Gritsch, Daniel R. Zollinger, Nicole Ortogero, Joseph M. Beechem, G. Petur Nielsen, Ivan Chebib, Tu Nguyen-Ngoc, Michael Montemurro, Gregory M. Cote, Edwin Choy, Igor Letovanec, Stéphane Cherix, Nikhil Wagle, Peter K. Sorger, Alex B. Haynes, John T. Mullen, Ivan Stamenkovic, Miguel N. Rivera, Cigall Kadoch, Kai W. Wucherpfennig, Orit Rozenblatt-Rosen, Mario L. Suvà, Nicolò Riggi, Aviv Regev
Journal: Nature Medicine (2021)
FRI0122 Anti-ro/la antibodies and cumulative tissue damage (slicc/acr) in patients with systemic lupus erythematosus
Authors: L Carreño, FJ López-Longo, M Rodríguez-Mahou, CM González, AI Turrión, CA Montilla, M Moreno-Zazo, N Caro, R Del Castillo, C González-Montagut, L Cebrián, I Monteagudo
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To calculate SLICC/ACR score for a cohort of patients with systemic lupus erythematosus (SLE) and evaluate its relation with the presence of anti-ENA antibodies (U1-RNP, Sm, Ro, and La), anticardiolipin antibodies, and clinical activity at the onset of the disease. <h3>Methods</h3> We calculated the SLICC scores of 236 patients diagnosed as SLE between 1988 and 2000. Anti-ENA antibodies were studied by ELISA in the first available serum sample of each patient. The SLE disease activity index (SLEDAI) of the first hospital study was calculated retrospectively. <h3>Results</h3> The mean age of our patients was 39 years (SD 15.8) and the mean duration of disease was 9.7 years (SD 6.9). Eighty-nine percent of the study population were women (211 of 239). Ninety-six patients (40.7%) scored zero, 90 (38.1%) scored 1 or 2, and 50 (21.2%) scored over 2. The main disorders were renal (66; 28%), neuropsychiatric (52; 22%), musculoskeletal (36; 15,3%), and vascular (35; 14.8%). The SLICC score obtained at &nbsp;the last follow-up visit was unrelated to age or the duration of SLE, but it correlated with the initial SLEDAI score (Spearman p &lt; 0.05); the higher the initial SLEDAI score, the higher the SLICC score at the end of follow-up. The SLICC score was significantly lower (Mann Whitney p &lt; 0.05) in patients with anti-ENA antibodies, particularly those who had anti-Ro/SS-A (mean 1.11 vs 1.79) or anti-La/SS-B antibodies (mean 0.52 vs 1.7). SLICC score showed no relation with anticardiolipin antibodies. The 8 patients who died in the course of the study had significantly higher SLICC scores (mean 2.87 vs 1.44). <h3>Conclusion</h3> High SLEDAI score at the onset of SLE and the absence of anti-ENA antibodies, particularly anti-Ro/SS-A or anti-La/SS-B antibodies were associated with significantly higher SLICC scores, suggesting that these factors may indicate poor prognosis in SLE.
FRI0208 Coexpression of th1 and th2-associated chemokine receptors in t cells infiltrating early fibrotic skin in a sle patient
Authors: C Chizzolini, M Hess, MG Uguccioni, M Baggiolini, JM Dayer, P Loetscher
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Fibrotic skin changes in systemic sclerosis (SSc) and allied conditions characteristically are preceded by an inflammatory infiltrate rich in T cells. It is not known whether recruited T cells induce fibrosis or react to developing fibrosis. <h3>Objectives</h3> Chemokines (CC) are involved in cell recruitment into inflammatory sites. Our aim was to characterise the CC receptor (R) usage as well as the effector function of T cells infiltrating a developing fibrotic skin lesion in a SLE patient. <h3>Methods</h3> T cells from a lesional skin biopsy were grown <i>in vitro</i> in the presence of IL-2. TcR, accessory molecules, and CCR expression were analysed by flow cytometry and RNase protection assay. The capacity to release interferon-g (IFN-g) and IL-4 was assessed upon CD3-crosslinking in phenotypically homogeneous T cell lines or clones. The chemotactic responses to synthetic CC was assessed. Immunohistochemistry was performed on the same tissue. <h3>Results</h3> T cells infiltrating the affected skin were heterogeneous in terms of accessory molecules (CD4<sup>+</sup>, CD8<sup>+</sup>, and CD4CD8 double negative) as well as of TcR (a/b and g/d) expression. The majority preferentially produced IFN-g, while a minority produced both IFN-g and IL-4. Preferential expression of type-1-related CXCR3 (and response to relevant CC) was observed and confirmed by tissue immunohistochemistry. Interestingly, several T cells coexpressed type 1 and type 2-related CCR and migrated to an equivalent extent in response to specific ligands. <h3>Conclusion</h3> The analysis performed on T cells infiltrating a novel fibrotic skin lesion from a SLE patient has revealed heterogeneous expression of CC receptors by T cells preferentially producing IFN-gamma. Since IFN-gamma exerts a potent inhibitory activity on ECM deposition by fibroblasts, these results hint to a reactive mechanisms aimed to control the extent of fibrosis. <h3>Reference</h3> Chizzolini C, Rezzonico R, Ribbens C, Burger D, Wollheim FA, Dayer J-M. Inhibition of type I collagen production by dermal fibroblasts upon contact with activated T cells. Different sensitivity to inhibition of systemic sclerosis and control fibroblasts. Arthitis Rheum. 1998;41:2039–47
Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization
Authors: Zhuoming Liu, Laura A. VanBlargan, Louis-Marie Bloyet, Paul W. Rothlauf, Rita E. Chen, Spencer Stumpf, Haiyan Zhao, John M. Errico, Elitza S. Theel, Mariel J. Liebeskind, Brynn Alford, William J. Buchser, Ali H. Ellebedy, Daved H. Fremont, Michael S. Diamond, Sean P.J. Whelan
Journal: Cell Host & Microbe (2021)
Naltrexone utilization for alcohol use disorder (AUD) during COVID-19 in an urban county population
Authors: D. Ayyala, M. Pimienta, T. Bottyan, C. Tien, J. L. Gonzalez, J. Dodge, N. Terrault, H. H. Han
Journal: Hepatology (2020)

Background: With the COVID-19 pandemic, social isolation, increased personal stressors, and less access to addiction support services may be detrimental to persons with AUD, including those with alcohol-associated liver disease We hypothesized that utilization of AUD pharmaceuticals such as naltrexone might increase during this time period We characterized the patterns of naltrexone prescriptions for AUD, particularly in reference to 'shelter-in-place' orders, amongst patients in a large, urban safety-net hospital Methods: Naltrexone prescriptions for AUD from Jan-May in 2019 and 2020 were compared as the shelter-in-place order occurred in March 2020 Patient and prescriber characteristics were extracted from the medical records Liver disease was determined by diagnostic codes, imaging and calculated FIB- 4 Linear regression assessed trends in monthly prescription numbers Results: A total of 128 adults were prescribed naltrexone: 81 from Jan-May 2020 compared to 47 in the same period in 2019 (Figure) The cohort was 72% male, 75% Hispanic, mean age of 46 years, 70% had steatosis on imaging, 25% had a FIB-4 >3 and 15% had cirrhosis  Patients were similar by year, except for a higher proportion with FIB-4>3 in 2019 vs 2020 (80% vs 20%, p <0 03)  In total, 77% received oral formulations (versus intramuscular) of naltrexone in a variety of care settings (78% primary care, 9% emergency room, 13% inpatient), with inpatient prescriptions higher but not statistically significant in 2020 versus 2019 (35% versus 0%, p=0 15) The number of prescriptions per month in January to March 2020 increased 2 2-3 3-fold over the same months in 2019 (Figure), reflecting a mean of 7 4 more naltrexone prescriptions per month in 2020 versus 2019 (p=0 04) Despite this, 2020 showed a mean decline of 5 3 prescriptions per month from February (the highest prescribing month) to May (p= 0 02) coinciding with the COVID-19 pandemic and county shelter-in-place orders Conclusion: A striking increase in naltrexone prescribing for AUD occurred in early 2020 and an increased proportion from inpatient settings, peaking with the onset of the 'shelter-inplace' order in the county An increase in patients with AUD, a lack of outpatient access to AUD services, or greater provider motivation/comfort with prescribing AUD pharmaceuticals may underlie this increase A subsequent decline in recent months may reflect fear of patients to access healthcare services during COVID-19, though other factors may be contributing Understanding these trends and factors can inform care of these patients during and beyond pandemic periods
Extracorporeal Membrane Oxygenation and Coronavirus Disease 2019
Authors: Johannes Kalbhenn, Hans-Joachim Priebe
Journal: JAMA Surgery (2021)

Asif K. Mustafa, MD, PhD; Philip J. Alexander, MD; Devang J. Joshi, MD; Deborah R. Tabachnick, MD; Chadrick A. Cross, MD; Pat S. Pappas, MD; Antone J. Tatooles, MD
Association Between Receipt of Unemployment Insurance and Food Insecurity Among People Who Lost Employment During the COVID-19 Pandemic in the United States
Authors: Julia Raifman, Jacob Bor, Atheendar Venkataramani
Journal: JAMA Network Open (2021)

More than 50 million US residents have lost work during the coronavirus disease 2019 (COVID-19) pandemic, and food insecurity has increased.To evaluate the association between receipt of unemployment insurance, including a $600/wk federal supplement between April and July, and food insecurity among people who lost their jobs during the COVID-19 pandemic.This cohort study used difference-in-differences analysis of longitudinal data from a nationally representative sample of US adults residing in low- and middle-income households (ie, <$75 000 annual income) who lost work during the COVID-19 pandemic. Data were from 15 waves of the Understanding Coronavirus in America study (conducted April 1 to November 11, 2020).Receipt of unemployment insurance benefits.Food insecurity and eating less due to financial constraints, assessed every 2 weeks by self-report.Of 2319 adults living in households earning less than $75 000 annually and employed in February 2020, 1119 (48.3%) experienced unemployment during the COVID-19 pandemic and made up our main sample (588 [53.6%] White individuals; mean [SD] age 45 [15] years; 732 [65.4%] women). Of those who lost employment, 415 (37.1%) reported food insecurity and 437 (39.1%) reported eating less due to financial constraints in 1 or more waves of the study. Among people who lost work, receipt of unemployment insurance was associated with a 4.3 (95% CI, 1.8-6.9) percentage point decrease in food insecurity (a 35.0% relative reduction) and a 5.7 (95% CI, 3.0-8.4) percentage point decrease in eating less due to financial constraints (a 47.8% relative reduction). Decreases in food insecurity were larger with the $600/wk supplement and for individuals who were receiving larger amounts of unemployment insurance.In this US national cohort study, receiving unemployment insurance was associated with large reductions in food insecurity among people who lost employment during the COVID-19 pandemic. The $600/wk federal supplement and larger amounts of unemployment insurance were associated with larger reductions in food insecurity.
Targetting CD38 in T Cell Acute Lymphoblastic Leukemia
Authors: Karen L. Bride, Tiffaney L. Vincent, Soo-Yeon Im, David M. Barrett, Michelle L. Hermiston, Terzah M. Horton, Mignon L. Loh, Shannon L Maude, Stephan A Grupp, Brent Wood, David T Teachey
Journal: Blood (2017)
Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial
Authors: Barry Dixon, Roger J Smith, Duncan J Campbell, John L Moran, Gordon S Doig, Thomas Rechnitzer, Christopher M MacIsaac, Nicholas Simpson, Frank M P van Haren, Angajendra N Ghosh, Sachin Gupta, Emma J C Broadfield, Timothy M E Crozier, Craig French, John D Santamaria
Journal: The Lancet Respiratory Medicine (2021)
Poverty, precarious work, and the COVID-19 pandemic: lessons from Bolivia
Authors: Calla Hummel, Felicia Marie Knaul, Michael Touchton, V Ximena Velasco Guachalla, Jami Nelson-Nuñez, Carew Boulding
Journal: The Lancet Global Health (2021)

Bolivia is one of the poorest countries in Latin America with a gross domestic product of around US$3500 per capita, health spending of approximately $220 per capita, a labour market dominated by informal work, and a weak health system. However, in the response to COVID-19, Bolivia has fared better than other health systems in the region and provides insight with regard to the implementation of subnational non-pharmaceutical interventions and supporting workers without social protection.
Evaluating the clinical utility of universal screening to identify Lynch syndrome in stage III/III colorectal cancer patients: A prospective observational study in Japan.
Authors: Yasuaki Yamamoto, Yuichiro Tsukada, Takeshi Kuwata, Motohiro Kojima, Yumie Hiraoka, Hiroya Taniguchi, Hideaki Bando, Takahiro Yoshioka, Takeshi Sasaki, Yuji Nishizawa, Koji Ikeda, Kiwamu Akagi, Takayuki Yoshino, Masaaki Ito
Journal: Journal of Clinical Oncology (2021)

41 Background: Universal screening for Lynch syndrome (LS) by identifying deficient DNA mismatch repair (MMR) in the tumor tissue of all new colorectal cancer (CRC) patients is widely accepted. The population prevalence of LS is approximately 3% in Western countries, whereas it is approximately 0.7% in Japan. In addition, the number of relatives diagnosed per proband is 3.6 in Western countries, whereas there are even fewer diagnoses per proband in Japan. To address the issue of LS remaining largely underdiagnosed in Japan, we prospectively evaluated the clinical utility of universal screening of LS in CRC patients. Methods: From March 2016 to August 2019, all consecutive new cases of stage II/III CRC underwent immunohistochemistry (IHC) screening for MMR using MLH1, MSH2, MSH6, and PMS2 antibodies. The patients negative for both MLH1 and PMS2 (MLH1-/PMS2-) were subjected to reflex testing for BRAF V600E mutation. Patients with both MLH1-/PMS2- and BRAF negative (cohort A, n = 14) and those with other IHC patterns (cohort B, n = 13) were referred for genetic counseling (GC) and genetic testing (GT). Furthermore, relatives of probands with confirmed LS were referred for GC/GT if they were willing. Results: Overall, 591 pts were enrolled in this study. Patient background were as follows: &gt; 70 y/o, 35%; right-sided/left-sided colon/rectum, 24%/24%/53%; and cStage II/III, 65%/35%. Of 591 patients, 40 (6.8%) had MMR deficiency. Of 27 patients with MLH1-/PMS2-, 24 underwent BRAF reflex testing; only 10 of these patients tested positive for mutation. Of 27 patients recommended for GC, 25 were referred for GC and 22 for GT, which revealed 12 LS cases (2%, mutation genes:MLH1/PMS2/MSH2; 4/2/6). The frequency of LS diagnosis with respect to patient background was as follows: &gt; 70/≤70 y, 1.0/2.6%; right-sided/left-sided colon/rectum, 5.8/0/1.3%; and cStage II/III, 2.6/1.0%. Interestingly, only 3 (25%) of 12 patients who underwent GC/GT in cohort A had LS compared with 9 (90%) of 10 patients in cohort B ( p= 0.004). Moreover, among 11 relatives of 5 families who were willing to undergo GC/GT, six (55%) had LS, of whom two were first-degree relatives (33%), one was a second-degree relative (50%), and three were third-degree relatives (100%). Conclusions: This study showed that universal screening of LS in CRC patients is significantly useful in Japan. Furthermore, implementing a reflex testing strategy demonstrated high adherence to guidelines and the appropriateness of our referrals for GC/GT.
Third-line therapy in metastatic renal cell carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC).
Authors: Daniel Yick Chin Heng, Igor Stukalin, Connor Wells, Frede Donskov, Brian I. Rini, Jae-Lyun Lee, Georg A. Bjarnason, Benoit Beuselinck, Martin Smoragiewicz, Ajjai Shivaram Alva, Sandy Srinivas, Lori Wood, James Brugarolas, Sumanta Kumar Pal, Takeshi Yuasa, Reuben James Broom, Ravindran Kanesvaran, Aristotelis Bamias, Jennifer J. Knox, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2015)

e15578 Background: Third line targeted therapy efficacy in mRCC is not well characterized and is not reimbursed in many jurisdictions worldwide. Methods: The IMDC consists of consecutive patient series from 25 international cancer centers. It was queried for specific sequences of targeted therapy and third-line therapy. Kaplan Meier estimates were used for survival and proportional hazards regression used to adjust hazard ratios for confounders. Results: 4,450 patients were treated with first-line targeted therapy, of which 2,112 (48%) had second-line therapy and 920 (21%) had third-line targeted therapy. The most common third line therapies were everolimus 26%, sorafenib 13%, sunitinib 13%, temsirolimus 11%, pazopanib 11%, and axitinib 6%. IMDC prognostic groups (Heng et al JCO 2009) and their associated survivals (both determined from third line therapy initiation) were 6% favorable risk (OS 20.1 (14.7-32.6), PFS 6.3 (4.4-12.0)), 67% intermediate risk (OS 15.0 (12.2-16.9), PFS 3.6 (3.2-4.1)) and 27% poor risk (OS 5.5 (4.5-6.5), PFS 2.5 (1.8-3.0)). Overall response rate for third-line therapy was 10.4% and 50.4% had stable disease in those patients that were evaluable (n=516). Median PFS was 3.4 months (95%CI 3.2-3.7) and median OS from third line therapy initiation was 12.4 months (95%CI 11.1-13.4). Table illustrates PFS and OS for each therapy from time of third-line therapy initiation. On multivariable analysis adjusting for IMDC criteria, the hazard ratios for death between the different 3rd line therapies were not statistically significant. Conclusions: Third line targeted therapy has demonstrated activity, is prevalent in use, and should be offered to clinically eligible patients. One agent does not appear to be superior to another in this series. Further studies are required to determine appropriate sequencing. 3rd line therapy PFS (months 95%CI) OS (months 95%CI) Axitinib 4.4 (2.8-5.1) 15.5 (9.4-20.6) Everolimus 3.4 (2.9-3.9) 12.1 (10.1-14.1) Pazopanib 3.5 (2.7-5.0) 13.8 (11.0-19.5) Sorafenib 3.5 (2.9-4.1) 12.5 (10.9-17.1) Sunitinib 4.1 (3.0-5.4) 10.7 (8.0-14.7) Temsirolimus 3.2 (2.5-3.7) 9.9 (7.2-12.5)
Prognostic impact of chemoradiation-related lymphopenia in patients with locally advanced pancreatic cancer.
Authors: Daniel W Kim, Grace Lee, Colin D. Weekes, David P. Ryan, Aparna Raj Parikh, Jill N. Allen, Motaz Qadan, Cristina R. Ferrone, Carlos Fernandez-del Castillo, William L. Hwang, Theodore S. Hong, Jennifer Y Wo
Journal: Journal of Clinical Oncology (2021)

439 Background: Chemoradiation (CRT) induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. The objective of this study was to evaluate the prognostic impact of lymphopenia in patients with nonmetastatic, unresectable pancreatic ductal adenocarcinoma (PDAC) treated by neoadjuvant FOLFIRINOX (5-fluorouracil [5FU]/leucovorin/irinotecan/oxaliplatin) followed by CRT. We hypothesized that severe lymphopenia would correlate with worse survival. Methods: The inclusion criteria for this single-institution retrospective study were: 1) biopsy-proven diagnosis of unresectable PDAC, 2) absence of distant metastasis, 3) receipt of neoadjuvant FOLFIRINOX followed by CRT, and 4) absolute lymphocyte count (ALC) available prior to and two months after initiating CRT. In general, CRT consisted of 5FU or capecitabine and RT with 58.8 Gy over 28 fractions. Lymphopenia was graded according to CTCAE v5.0. The primary variable of interest was lymphopenia at two months, dichotomized by ALC of &lt; 0.5/μl (Grade 3 lymphopenia). The primary endpoint was overall survival (OS). Cox modeling and Kaplan-Meier methods were used to perform survival analyses. Results: A total of 138 patients were identified. Median follow-up for the entire cohort was 16 months. Median age was 65. Fifty-six percent were female, 86% were Caucasian, and 97% had ECOG ≤1. Median tumor size was 3.8 cm. Tumor location was pancreatic head in 63%, body in 22%, tail in 8%, and neck in 7%. Median baseline ALC for the entire cohort was 1.5 k/ul. Two months after initiating CRT, 106 (77%) had severe (Grade 3 or worse) lymphopenia. While there were no significant differences in baseline patient or disease characteristics, patients with severe lymphopenia received higher doses of RT with longer duration of treatment compared to those without severe lymphopenia. On multivariable Cox model, severe lymphopenia at two months was significantly associated with increased hazards of death (HR = 4.00 [95% CI 2.03-7.89], p &lt; 0.001). Greater number of neoadjuvant FOLFIRINOX cycles received prior to CRT was associated with lower hazards of death (HR = 0.84 [95% CI 0.77-0.92], p &lt; 0.001). The 12-month OS was 73% vs. 90% in the cohort with vs. without severe lymphopenia, respectively (log-rank p &lt; 0.001). Conclusions: Treatment-related lymphopenia is common and severe lymphopenia may be a prognostic marker of poorer survival in locally advanced pancreatic cancer. Closer observation in high-risk patients and minimization of RT dose and duration are potential approaches to mitigating CRT-related lymphopenia. Our findings also suggest an important role of the host immunity in pancreatic cancer outcomes, supporting the ongoing efforts of immunotherapy trials in pancreatic cancer.
Specific Dimensions of Depression Have Different Associations With Cognitive Decline in Older Adults With Type 2 Diabetes
Authors: Laili Soleimani, Ramit Ravona-Springer, Hung-Mo Lin, Xiaoyu Liu, Mary Sano, Anthony Heymann, Michal Schnaider Beeri
Journal: Diabetes Care (2021)

OBJECTIVE Depression is highly frequent in older adults with type 2 diabetes and is associated with cognitive impairment, yet little is known about how various depression dimensions differentially affect cognition. We investigated longitudinal associations of specific depression dimensions with cognitive decline. RESEARCH DESIGN AND METHODS Participants (N = 1,002) were from the Israel Diabetes and Cognitive Decline study, were ≥65 years of age, had type 2 diabetes, and were not experiencing dementia at baseline. Participants underwent a comprehensive neuropsychological battery at baseline and every 18 months thereafter, including domains of episodic memory, attention/working memory, semantic categorization/language, and executive function, and Z-scores of each domain were averaged and further normalized to calculate global cognition. Depression items from the 15-item Geriatric Depression Scale were measured at each visit and subcategorized into five dimensions: dysphoric mood, withdrawal-apathy-vigor (entitled apathy), anxiety, hopelessness, and memory complaint. Random coefficients models examined the association of depression dimensions with baseline and longitudinal cognitive functioning, adjusting for sociodemographics and baseline characteristics, including cardiovascular risk factors, physical activity, and use of diabetes medications. RESULTS In the fully adjusted model at baseline, all dimensions of depression, except for anxiety, were associated with some aspect of cognition (P values from 0.01 to &amp;lt;0.001). Longitudinally, greater apathy scores were associated with faster decline in executive function (P = 0.004), a result that withstood adjustment for multiple comparisons. Associations of other depression dimensions with cognitive decline were not significant (P &amp;gt; 0.01). CONCLUSIONS Apathy was associated with a faster cognitive decline in executive function. These findings highlight the heterogeneity of depression as a clinical construct rather than as a single entity and point to apathy as a specific risk factor for cognitive decline among older adults with type 2 diabetes.