tbuckley/cabot-search huggingface dataset:
ERCC1, VEGF along with clinical variants impact the outcome of advanced non-small cell lung cancer (NSCLC) patients
Authors: N. F. Abdel Karim, H. X. Bui, N. Patil, P. Pathrose, M. Rao, A. Mostafa, A. Mehta, M. Anderson
Journal: Journal of Clinical Oncology (2009)

e22129 Background: ERCC1 is a useful marker of resistance to cisplatin and its analogues. Longer survival was noted in patients with ERCC1 negative expression when treated with platinum. VEGF and its receptor-KDR previously indicated poor prognosis with high tumor cell expression. Methods: From 1998–2008, a retrospective study included 32 patients with advanced NSCLC, where clinical variants as well as the levels of expression of VEGF and VEGFR using rabbit monoclonal Ab (VEGF: A-20, 1:100, SCBT; VEGFR: 55B11, 1:250, cell signaling) and immunohistochemistry for ERCC1 (Mouse monoclonal ab-8F1, Thermo Scientific, 1:200) were measured and co-related to the overall survival of those patients using Cox proportional hazards model. Results: Of the 32 patients, six received non-platinum and twenty six received platinum based regimens either first line or later. Eight patients were females (25%), three were African Americans (9%) and the median age was 62.5 (42–84). Females had a significantly higher overall survival; median survival of 30 months compared to 10.6 months for males (p=0.00089). There was no significant correlation between age and survival (p=0.2). Well differentiated NSCLC of any subtype showed better survival (p=0.04). VEGF low expression correlated with better overall survival (p=0.021). Among the 26 patients who received platinum based regimens, 11 (42%) were ERCC1 negative, 10 had strongly positive ERCC1 expression (39%) and 5 patients had weakly positive ERCC1 expression (19%). ERCC1 negativity was strongly associated with longer survival (p=0.0019) in patients treated with platinum based regimens, where patients treated with the first line platinum had better survival (p=0.034). VEGFR low expression was associated with longer survival in the same group of patients (p=0.013). Caucasians had better overall survival in comparison to African Americans (p=0.007). Higher White blood cell counts and platelet counts were associated with lower survival (p=0.0019 and 0.065 respectively). Conclusion: ERCC1 negativitiy with the first line platinum therapy, VEGF low expression, females, Caucasians as well as the absence of elevation of White blood cells and platelet counts correlate with improved overall survival in advanced NSCLC. No significant financial relationships to disclose.
Supplemented ERA-EDTA Registry data evaluated the frequency of dialysis, kidney transplantation, and comprehensive conservative management for patients with kidney failure in Europe
Authors: Vianda S. Stel, Rianne W. de Jong, Anneke Kramer, Anton M. Andrusev, José M. Baltar, Myftar Barbullushi, Samira Bell, Pablo Castro de la Nuez, Harijs Cernevskis, Cécile Couchoud, Johan De Meester, Bjørn O. Eriksen, Liliana Gârneaţă, Eliezer Golan, Jaakko Helve, Marc H. Hemmelder, Kristine Hommel, Kyriakos Ioannou, Faiçal Jarraya, Nino Kantaria, Julia Kerschbaum, Kirill S. Komissarov, Ángela Magaz, Lucile Mercadal, Mai Ots-Rosenberg, Runólfur Pálsson, Axel Rahmel, Helena Rydell, Manuela Savino, Nurhan Seyahi, Maria F. Slon Roblero, Olivera Stojceva-Taneva, Arjan van der Tol, Evgueniy S. Vazelov, Edita Ziginskiene, Óscar Zurriaga, Raymond C. Vanholder, Ziad A. Massy, Kitty J. Jager
Journal: Kidney International (2021)

The aims of this study were to determine the frequency of dialysis and kidney transplantation and to estimate the regularity of comprehensive conservative management (CCM) for patients with kidney failure in Europe. This study uses data from the ERA-EDTA Registry. Additionally, our study included supplemental data from Armenia, Germany, Hungary, Ireland, Kosovo, Luxembourg, Malta, Moldova, Montenegro, Slovenia and additional data from Israel, Italy, Slovakia using other information sources. Through an online survey, responding nephrologists estimated the frequency of CCM (i.e. planned holistic care instead of kidney replacement therapy) in 33 countries. In 2016, the overall incidence of replacement therapy for kidney failure was 132 per million population (pmp), varying from 29 (Ukraine) to 251 pmp (Greece). On 31 December 2016, the overall prevalence of kidney replacement therapy was 985 pmp, ranging from 188 (Ukraine) to 1906 pmp (Portugal). The prevalence of peritoneal dialysis (114 pmp) and home hemodialysis (28 pmp) was highest in Cyprus and Denmark respectively. The kidney transplantation rate was nearly zero in some countries and highest in Spain (64 pmp). In 28 countries with five or more responding nephrologists, the median percentage of candidates for kidney replacement therapy who were offered CCM in 2018 varied between none (Slovakia and Slovenia) and 20% (Finland) whereas the median prevalence of CCM varied between none (Slovenia) and 15% (Hungary). Thus, the substantial differences across Europe in the frequency of kidney replacement therapy and CCM indicate the need for improvement in access to various treatment options for patients with kidney failure.
Multiorgan failure with abnormal receptor metabolism in mice mimicking Samd9/9L syndromes
Authors: Akiko Nagamachi, Akinori Kanai, Megumi Nakamura, Hiroshi Okuda, Akihiko Yokoyama, Satoru Shinriki, Hirotaka Matsui, Toshiya Inaba
Journal: Journal of Clinical Investigation (2020)

Autosomal dominant sterile α motif domain containing 9 (Samd9) and Samd9L (Samd9/9L) syndromes are a large subgroup of currently established inherited bone marrow failure syndromes that includes myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital phenotypes, and enteropathy (MIRAGE), ataxia pancytopenia, and familial monosomy 7 syndromes. Samd9/9L genes are located in tandem on chromosome 7 and have been known to be the genes responsible for myeloid malignancies associated with monosomy 7. Additionally, as IFN-inducible genes, Samd9/9L are crucial for protection against viruses. Samd9/9L syndromes are caused by gain-of-function mutations and develop into infantile myelodysplastic syndromes associated with monosomy 7 (MDS/-7) at extraordinarily high frequencies. We generated mice expressing Samd9LD764N, which mimic MIRAGE syndrome, presenting with growth retardation, a short life, bone marrow failure, and multiorgan degeneration. In hematopoietic cells, Samd9LD764N downregulates the endocytosis of transferrin and c-Kit, resulting in a rare cause of anemia and a low bone marrow reconstitutive potential that ultimately causes MDS/-7. In contrast, in nonhematopoietic cells we tested, Samd9LD764N upregulated the endocytosis of EGFR by Ship2 phosphatase translocation to the cytomembrane and activated lysosomes, resulting in the reduced expression of surface receptors and signaling. Thus, Samd9/9L is a downstream regulator of IFN that controls receptor metabolism, with constitutive activation leading to multiorgan dysfunction.
Immune Checkpoint Inhibitor-Associated Myocarditis With Persistent Troponin Elevation Despite Abatacept and Prolonged Immunosuppression
Authors: Shiying Liu, Joyce Chan, Davor Brinc, Sonal Gandhi, Aaron Izenberg, Diego Delgado, Husam Abdel-Qadir, Bernd J. Wintersperger, Paaladinesh Thavendiranathan
Journal: JACC CardioOncology (2020)
Development of Endocrine Function in the Human Placenta and Fetus
Authors: Dorothy B. Villee
Journal: New England Journal of Medicine (1969)

GoandsThe fetal gonads develop from proliferating coelomic epithelium as did the fetal adrenal glands (Table 1). Longitudinal ridges, the gonadal ridges, develop on each side of the midline on the medial surface of the mesonephros between the mesonephros and dorsal mesentery. At four weeks of age these ridges are first apparent and are situated just posterior to the developing fetal adrenal cortex. The remarkable similarity of steroid metabolism in the gonads and adrenal glands is not so surprising when one considers the proximity of the primordial cells from which these glands develop. There are no germ cells in the . . .
Evaluation of Changes in Beverage Prices and Volume Sold Following the Implementation and Repeal of a Sweetened Beverage Tax in Cook County, Illinois
Authors: Lisa M. Powell, Julien Leider
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Health taxes are policy tools used to reduce harmful consumption of products and raise tax revenue, and they may also be associated with signaling (ie, informational and educational) factors that enhance their impact. <h3>Objectives</h3> To examine changes in prices and volume sold of sweetened beverages following the implementation and repeal of the Cook County, Illinois, Sweetened Beverage Tax (SBT) compared with the comparison site of St Louis County and city, Missouri, which did not impose a tax. <h3>Design, Setting, and Participants</h3> This study used interrupted time series analyses to assess changes in price and volume sold of taxed (based on beverage type and sweetener status) and untaxed beverages in Cook County compared with St Louis following the implementation of the SBT on August 2, 2017, and its repeal effective December 1, 2017. Statistical analysis was performed from January to June 2020. <h3>Exposures</h3> Implementation and repeal of the Cook County SBT. <h3>Main Outcomes and Measures</h3> Changes in taxed and untaxed beverage prices and volume sold. Nielsen food store scanner data were obtained for weekly volume and dollar amount sold of nonalcoholic beverage universal product codes (UPCs) for each site in supermarkets and mass merchandise, grocery, drug, convenience, and dollar stores. <h3>Results</h3> The analytic samples included 16 510 UPCs for volume and 2141 UPCs (balanced sample) for prices for 122 pretax weeks, 16 tax weeks, and 35 postrepeal weeks. Compared with St Louis, posttax implementation in Cook County resulted in a level increase in taxed beverage prices of 1.13 cents per fluid ounce (95% CI, 1.01 to 1.25 cents per fluid ounce), representing a slight overshifting, followed by a posttax repeal level decrease of −1.19 cents per fluid ounce (95% CI, −1.33 to −1.04 cents per fluid ounce), with no resulting change pretax to posttax repeal. Volume sold of taxed beverages in Cook County compared with St Louis exhibited a posttax implementation level decrease of 25.7% (β = −0.297; 95% CI, −0.415 to −0.179) and a posttax repeal level increase of 30.5% (β = 0.266, 95% CI, 0.124 to 0.408), with no net change in volume sold from pretax to 8 months after repeal. <h3>Conclusions and Relevance</h3> This study using interrupted time series analysis found no net change in volume sold of taxed beverages following the implementation and repeal of the Cook County SBT, suggesting the tax had no signaling association. Repeals of such taxes may fully reverse their associations with reduced demand and harms associated with sweetened beverage intake.
Prognostic validation and clinical implications of the EANO ESMO classification of leptomeningeal metastasis from solid tumors
Authors: Emilie Le Rhun, Patrick Devos, Johannes Weller, Katharina Seystahl, Francesca Mo, Annette Compter, Anna S Berghoff, Joost L M Jongen, Fabian Wolpert, Roberta Rudà, Dieta Brandsma, Martin van den Bent, Matthias Preusser, Ulrich Herrlinger, Michael Weller
Journal: Neuro-Oncology (2020)

The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) from solid cancers based on clinical, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) cytology presentation. MRI patterns are classified as linear, nodular, both, or neither. Type I LM is defined by positive CSF cytology (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these LM subtypes.
Solitary Use of Alcohol and Marijuana by US 12th Grade Students, 1976-2019
Authors: Yvonne M. Terry-McElrath, Patrick M. O’Malley, Megan E. Patrick
Journal: JAMA Pediatrics (2020)

Conflict of Interest Disclosures: Drs Kaforou, Herberg, and Levin report a patent to a method of identifying a patient having a bacterial infection pending.Dr Levin reports a patent for RNA signature distiguishing bacterial and viral infection pending.
Marrow Stromal Cells Secrete FGF2 in Exosomes, Providing Paracrine Protection for Leukemia Cells from Kinase Inhibitors
Authors: Elie Traer, Brian J. Druker, Jakki Martinez, Nathalie Javidi-Sharifi, Isabel English, Anupriya Agarwal, Jennifer Dunlap
Journal: Blood (2017)
Successful closure of a rectovesical fistula after radical prostatectomy using endoscopic submucosal dissection combined with an over-the-scope clip
Authors: Timothee Wallenhorst, Charlène Brochard, Thomas Lambin, Mael Pagenault, Laurent Siproudhis, Guillaume Bouguen, Mathieu Pioche
Journal: Endoscopy (2020)

Rectovesical fistulas after prostatectomy are rare and difficult to manage, often requiring reconstructive surgery. Few cases of endoscopic treatment are currently reported with disappointing results [1]. Endoscopic submucosal dissection (ESD) of the fistula orifice combined with a clip closure has been described as effective for chronic oeso-tracheal [2] [3] and rectal [4] fistulas after surgery or Crohn's disease [5]. We report here the first success of this technique, with video illustration ([Video 1]), to treat a rectovesical fistula occurring after radical prostatectomy for adenocarcinoma.
Audio Interview: A Look at Covid-19 Prevention and Care in 2020
Authors: Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

A Look at Covid-19 Prevention and Care in 2020 In this audio interview conducted on December 30, 2020, the editors discuss the new mRNA-1273 vaccine against SARS-CoV-2, along with other studies of ...
Leukemic extracellular vesicles induce chimeric antigen receptor T cell dysfunction in chronic lymphocytic leukemia
Authors: Michelle J. Cox, Fabrice Lucien, Reona Sakemura, Justin C. Boysen, Yohan Kim, Paulina Horvei, Claudia Manriquez Roman, Michael J. Hansen, Erin E. Tapper, Elizabeth L. Siegler, Cynthia Forsman, Sydney B. Crotts, Kendall J. Schick, Mehrdad Hefazi, Michael W. Ruff, Ismail Can, Mohamad Adada, Evandro Bezerra, Lionel Aurelien Kankeu Fonkoua, Wendy K. Nevala, Esteban Braggio, Wei Ding, Sameer A. Parikh, Neil E. Kay, Saad S. Kenderian
Journal: Molecular Therapy (2021)

Chimeric antigen receptor (CAR) T cell therapy has yielded unprecedented outcomes in some patients with hematological malignancies; however, inhibition by the tumor microenvironment has prevented the broader success of CART cell therapy. We used chronic lymphocytic leukemia (CLL) as a model to investigate the interactions between the tumor microenvironment and CART cells. CLL is characterized by an immunosuppressive microenvironment, an abundance of systemic extracellular vesicles (EVs), and a relatively lower durable response rate to CART cell therapy. In this study, we characterized plasma EVs from untreated CLL patients and identified their leukemic cell origin. CLL-derived EVs were able to induce a state of CART cell dysfunction characterized by phenotypical, functional, and transcriptional changes of exhaustion. We demonstrate that, specifically, PD-L1+ CLL-derived EVs induce CART cell exhaustion. In conclusion, we identify an important mechanism of CART cell exhaustion induced by EVs from CLL patients. Chimeric antigen receptor (CAR) T cell therapy has yielded unprecedented outcomes in some patients with hematological malignancies; however, inhibition by the tumor microenvironment has prevented the broader success of CART cell therapy. We used chronic lymphocytic leukemia (CLL) as a model to investigate the interactions between the tumor microenvironment and CART cells. CLL is characterized by an immunosuppressive microenvironment, an abundance of systemic extracellular vesicles (EVs), and a relatively lower durable response rate to CART cell therapy. In this study, we characterized plasma EVs from untreated CLL patients and identified their leukemic cell origin. CLL-derived EVs were able to induce a state of CART cell dysfunction characterized by phenotypical, functional, and transcriptional changes of exhaustion. We demonstrate that, specifically, PD-L1+ CLL-derived EVs induce CART cell exhaustion. In conclusion, we identify an important mechanism of CART cell exhaustion induced by EVs from CLL patients.
Association of Long-Term Air Pollution with Prevalence and Incidence of Distal Sensorimotor Polyneuropathy: KORA F4/FF4 Study
Authors: Christian Herder, Alexandra Schneider, Siqi Zhang, Kathrin Wolf, Haifa Maalmi, Cornelia Huth, Regina Pickford, Michael Laxy, Gidon J. Bönhof, Wolfgang Koenig, Wolfgang Rathmann, Michael Roden, Annette Peters, Barbara Thorand, Dan Ziegler
Journal: Environmental Health Perspectives (2020)

Air pollution contributes to type 2 diabetes and cardiovascular diseases, but its relevance for other complications of diabetes, in particular distal sensorimotor polyneuropathy (DSPN), is unclear. Recent studies have indicated that DSPN is also increasingly prevalent in obesity.We aimed to assess associations of air pollutants with prevalent and incident DSPN in a population-based study of older individuals with high rates of type 2 diabetes and obesity.Cross-sectional analyses on prevalent DSPN were based on 1,075 individuals 62-81 years of age from the German Cooperative Health Research in the Region of Augsburg (KORA) F4 survey (2006-2008). Analyses on incident DSPN included 424 individuals without DSPN at baseline (KORA F4), of whom 188 had developed DSPN by the KORA FF4 survey (2013-2014). Associations of annual average air pollutant concentrations at participants' residences with prevalent and incident DSPN were estimated using Poisson regression models with a robust error variance adjusting for multiple confounders.Higher particle number concentrations (PNCs) were associated with higher prevalence [risk ratio (RR) per interquartile range (IQR) increase=1.10 (95% CI: 1.01, 1.20)] and incidence [1.11 (95% CI: 0.99, 1.24)] of DSPN. In subgroup analyses, particulate (PNC, PM10, PMcoarse, PM2.5, and PM2.5abs) and gaseous (NOx, NO2) pollutants were positively associated with prevalent DSPN in obese participants, whereas corresponding estimates for nonobese participants were close to the null [e.g., for an IQR increase in PNC, RR=1.17 (95% CI: 1.05, 1.31) vs. 1.06 (95% CI: 0.95, 1.19); pinteraction=0.22]. With the exception of PM2.5abs, corresponding associations with incident DSPN were positive in obese participants but null or inverse for nonobese participants, with pinteraction≤0.13 [e.g., for PNC, RR=1.28 (95% CI: 1.08, 1.51) vs. 1.03 (95% CI: 0.90, 1.18); pinteraction=0.03].Both particulate and gaseous air pollutants were positively associated with prevalent and incident DSPN in obese individuals. Obesity and air pollution may have synergistic effects on the development of DSPN. https://doi.org/10.1289/EHP7311.
Effects of Blood Flow Restriction Exercise and Possible Applications in Type 2 Diabetes
Authors: Nina Saatmann, Oana-Patricia Zaharia, Jeremy P. Loenneke, Michael Roden, Dominik H. Pesta
Journal: Trends in Endocrinology and Metabolism (2021)

Blood flow restriction resistance training (BFRT) employs partial vascular occlusion of exercising muscles via inflation cuffs. Compared with high-load resistance training, mechanical load is markedly reduced with BFRT, but induces similar gains in muscle mass and strength. BFRT is thus an effective training strategy for people with physical limitations. Recent research indicates that BFRT has beneficial effects on glucose and mitochondrial metabolism. BFRT may therefore qualify as a valuable exercise alternative for individuals with type 2 diabetes (T2D), a disorder characterized by impaired glucose metabolism, musculoskeletal decline, and exacerbated progression of sarcopenia. This review covers the effects of BFRT in healthy populations and in persons with impaired physical fitness, the mechanisms of action of this novel training modality, and possible applications for individuals with T2D.
A Genomic-Pathologic Annotated Risk Model to Predict Recurrence in Early-Stage Lung Adenocarcinoma
Authors: Gregory D. Jones, Whitney S. Brandt, Ronglai Shen, Francisco Sanchez-Vega, Kay See Tan, Axel Martin, Jian Zhou, Michael Berger, David B. Solit, Nikolaus Schultz, Hira Rizvi, Yuan Liu, Ariana Adamski, Jamie E. Chaft, Gregory J. Riely, Gaetano Rocco, Matthew J. Bott, Daniela Molena, Marc Ladanyi, William D. Travis, Natasha Rekhtman, Bernard J. Park, Prasad S. Adusumilli, David Lyden, Marcin Imielinski, Marty W. Mayo, Bob T. Li, David R. Jones
Journal: JAMA Surgery (2020)

Recommendations for adjuvant therapy after surgical resection of lung adenocarcinoma (LUAD) are based solely on TNM classification but are agnostic to genomic and high-risk clinicopathologic factors. Creation of a prediction model that integrates tumor genomic and clinicopathologic factors may better identify patients at risk for recurrence.
NICE guideline on long covid
Authors: Manoj Sivan, Sharon Taylor
Journal: BMJ (2020)

The covid-19 pandemic has killed over 1.6 million people worldwide, 1 caused the worst healthcare crisis of this century, and put a huge dent in our economies.The magnitude of the population still struggling with symptoms four weeks after their acute illness-commonly called "long covid"-is becoming obvious and demands urgent prioritisation to prevent a further blow to health systems and the healthcare workforce.Long covid is thought to occur in approximately 10% of people infected, 2 3 so there are likely more than 5 million people affected globally.The National Institute for Health and Care Excellence (NICE), the Scottish Intercollegiate Guidelines Network, and the Royal College of General Practitioners have developed a rapid guideline for managing the long term effects of covid-19 4 to assist long covid services being set up in the NHS 5 and elsewhere.A lack of systematic research means that the current guideline is necessarily preliminary, but it will be updated regularly as new evidence emerges-becoming a "living guideline."This approach is essential as the current guideline lacks important detail, including a comprehensive list of organ complications seen in patients with long covid, the investigations required, and specific interventions for these complications.