tbuckley/cabot-search huggingface dataset:
Tumor Microenvironment Is Critical for the Maintenance of Cellular States Found in Primary Glioblastomas
Authors: Allison R. Pine, Stefano M. Cirigliano, James G. Nicholson, Yang Hu, Amanda Linkous, Ken Miyaguchi, Lincoln Edwards, Richa Singhania, Theodore H. Schwartz, Rohan Ramakrishna, David J. Pisapia, Matija Snuderl, Olivier Elemento, Howard A. Fine
Journal: Cancer Discovery (2020)

Abstract Glioblastoma (GBM), an incurable tumor, remains difficult to model and more importantly to treat due to its genetic/epigenetic heterogeneity and plasticity across cellular states. The ability of current tumor models to recapitulate the cellular states found in primary tumors remains unexplored. To address this issue, we compared single-cell RNA sequencing of tumor cells from 5 patients across four patient-specific glioblastoma stem cell (GSC)–derived model types, including glioma spheres, tumor organoids, glioblastoma cerebral organoids (GLICO), and patient-derived xenografts. We find that GSCs within the GLICO model are enriched for a neural progenitor–like cell subpopulation and recapitulate the cellular states and their plasticity found in the corresponding primary parental tumors. These data demonstrate how the contribution of a neuroanatomically accurate human microenvironment is critical and sufficient for recapitulating the cellular states found in human primary GBMs, a principle that may likely apply to other tumor models. Significance: It has been unclear how well different patient-derived GBM models are able to recreate the full heterogeneity of primary tumors. Here, we provide a complete transcriptomic characterization of the major model types. We show that the microenvironment is crucial for recapitulating GSC cellular states, highlighting the importance of tumor–host cell interactions. See related commentary by Luo and Weiss, p. 907. This article is highlighted in the In This Issue feature, p. 890
Increasing incidence of young-onset colorectal cancers in the UK and rising mortality in rectal cancers
Authors: Karl King Yong, Moe Kyaw, Georgina Chadwick, Krishna Sundaram
Journal: Gut (2020)

We read the recent Gut publication by Vuik et al 1 reporting an increase in incidence of young-onset colorectal cancers (CRCs) in Europe over the last 25 years. However, the rise in incidence was not associated with a similar rise in mortality. This study extracted data from the national and regional European cancer registries from 20 European countries, between years 1990 and 2016. The author claimed that there is some variability among some European countries, and mortality data are not available from the UK. Therefore, we conducted a UK-specific population-based study on young colon and rectal cancer incidence and mortality.

We extracted data on young-onset colon and rectal cancer incidence and mortality between 1996 and 2016 from Cancer Research UK. Trends were analysed by Joinpoint Regression Programme expressed as average annual percentage change. Incidence of young-onset colon and rectal cancer increased significantly in both men (colon cancer: 3.9 …
Japan's HPV vaccine crisis: act now to avert cervical cancer cases and deaths
Authors: Heidi J Larson
Journal: The Lancet Public Health (2020)

In May, 2013, a cluster of adverse events suspected to be linked to HPV vaccination were reported in the Japanese media, prompting the Japanese Government to suspend proactive recommendations for the vaccine in June, 2013. Despite no evidence of a link with HPV vaccination being found in the local investigation, and calls by WHO and the global scientific community to resume active recommendation of the cancer-preventing vaccine, the proactive recommendation of HPV vaccination remains suspended in Japan.
Abstract 16164: Effect of Change in Cumulative Psychosocial Stressors on Change in Body Mass Index Over Time
Authors: Jonathan Z Butler, Eva M Durazo, Rimma Dushkes, Natalie Bea Slopen, David R Williams, Tiffany M Powell-Wiley, Julie E Buring, Michelle A Albert
Journal: Circulation (2019)

Introduction: Increased psychosocial stress and obesity are both associated with elevated risk of cardiovascular disease (CVD). However, the effect of change in cumulative psychosocial stressors (s...
Competence against insufficiency: Why are men mostly safe from a rare and deadly prostate cancer?
Authors: Grinu Mathew, Lloyd C. Trotman
Journal: The Journal of Experimental Medicine (2020)

Prostate cancer is a slow-growing disease, but not always. A highly rare and lethal form of the disease shows survival rates of less than a year. It is called squamous cell prostate carcinoma. In this issue of JEM, Hermanova et al. (https://doi.org/10.1084/jem.20191787) provide new findings in mouse demonstrating a strong genetic handle on both the reasons behind the rarity and the aggressiveness.
Erratum. Randomized Controlled Trial of Mobile Closed-Loop Control. Diabetes Care 2020;43:607–615
Authors: Boris Kovatchev, Stacey M. Anderson, Dan Raghinaru, Yogish C. Kudva, Lori M. Laffel, Carol Levy, Jordan E. Pinsker, R. Paul Wadwa, Bruce Buckingham, Francis J. Doyle, Sue A. Brown, Mei Mei Church, Vikash Dadlani, Eyal Dassau, Laya Ekhlaspour, Gregory P. Forlenza, Elvira Isganaitis, David W. Lam, John Lum, Roy W. Beck
Journal: Diabetes Care (2020)
The impact of residual mitral regurgitation after MitraClip therapy in functional mitral regurgitation
Authors: Daniel Reichart, Daniel Kalbacher, Nicole Rübsamen, Eike Tigges, Christina Thomas, Johannes Schirmer, Hermann Reichenspurner, Stefan Blankenberg, Lenard Conradi, Ulrich Schäfer, Edith Lubos
Journal: European Journal of Heart Failure (2020)
Health and Climate Impacts of Scaling Adoption of Liquefied Petroleum Gas (LPG) for Clean Household Cooking in Cameroon: A Modeling Study
Authors: Chris Kypridemos, Elisa Puzzolo, Borgar Aamaas, Lirije Hyseni, Matthew Shupler, Kristin Aunan, Daniel Pope
Journal: Environmental Health Perspectives (2020)

The Cameroon government has set a target that, by 2030, 58% of the population will be using Liquefied Petroleum Gas (LPG) as a cooking fuel, in comparison with less than 20% in 2014. The National LPG Master Plan (Master Plan) was developed for scaling up the LPG sector to achieve this target.This study aimed to estimate the potential impacts of this planned LPG expansion (the Master Plan) on population health and climate change mitigation, assuming primary, sustained use of LPG for daily cooking.We applied existing and developed new mathematical models to calculate the health and climate impacts of expanding LPG primary adoption for household cooking in Cameroon over two periods: a) short-term (2017-2030): Comparing the Master Plan 58% target with a counterfactual LPG adoption of 32% in 2030, in line with current trends; and b) long-term (2031-2100, climate modeling only), assuming Cameroon will become a mature and saturated LPG market by 2100 (73% adoption, based on Latin American countries). We compared this with a counterfactual adoption of 41% by 2100, in line with current trends.By 2030, successful implementation of the Master Plan was estimated to avert about 28,000 (minimum=22,000, maximum=35,000) deaths and 770,000 (minimum=580,000maximum=1 million) disability-adjusted life years. For the same period, we estimated reductions in pollutant emissions of more than a third in comparison with the counterfactual, leading to a global cooling of -0.1 milli °C in 2030. For 2100, a cooling impact from the Master Plan leading to market saturation (73%) was estimated to be -0.70 milli °C in comparison with to the counterfactual, with a range of -0.64 to -0.93 milli °C based on different fractions of nonrenewable biomass.Successful implementation of the Master Plan could have significant positive impacts on population health in Cameroon with no adverse impacts on climate. https://doi.org/10.1289/EHP4899.
COVID-19 in a patient with systemic sclerosis treated with tocilizumab for SSc-ILD
Authors: Carina Mihai, Rucsandra Dobrota, Maria Schröder, Alexandru Garaiman, Suzana Jordan, Mike Oliver Becker, Britta Maurer, Oliver Distler
Journal: Annals of the Rheumatic Diseases (2020)

During the current global outbreak of coronavirus disease 2019 (COVID-19), risk stratification of patients is of utmost importance. Currently, patients >65 years and those with pre-existing medical conditions such as cardiovascular disease, chronic respiratory disease or diabetes mellitus are considered at higher risk for severe disease.1 The Swiss Federal Office of Public Health, like similar authorities around the world, has additionally included patients on immunosuppressants in the high-risk group for developing severe COVID-19.2 However, at this moment we do not have enough evidence either to support or to reject this assumption.

We report the case of a 57-year-old woman with systemic sclerosis (SSc) who developed COVID-19. Comorbidities were insulin-dependent type 2 diabetes mellitus and WHO grade I obesity. The anti-topoisomerase I antibody-positive patient was diagnosed with SSc in 2017. SSc-associated interstitial lung disease (SSc-ILD), with cough and exertion dyspnoea, was the leading organ manifestation, associated with symmetrical, non-erosive polyarthritis, and elevated acute phase reactants. Treatment with the anti-interleukin (IL) 6 receptor blocker tocilizumab, with 8 mg/kg body weight every 4 weeks intravenously, was started, leading to a good control of both …
Respiratory virus shedding in exhaled breath and efficacy of face masks
Authors: Nancy H. L. Leung, Daniel K. W. Chu, Eunice Y. C. Shiu, Kwok-Hung Chan, James J. McDevitt, Benien J. P. Hau, Hui-Ling Yen, Yuguo Li, Dennis K. M. Ip, J. S. Malik Peiris, Wing-Hong Seto, Gabriel M. Leung, Donald K. Milton, Benjamin J. Cowling
Journal: Nature Medicine (2020)
Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up
Authors: Lang Wang, Wenbo He, Xiaomei Yu, Dalong Hu, Mingwei Bao, Huafen Liu, Jiali Zhou, Hong Jiang
Journal: Journal of Infection (2020)

To investigate the characteristics and prognostic factors in the elderly patients with COVID-19.Consecutive cases over 60 years old with COVID-19 in Renmin Hospital of Wuhan University from Jan 1 to Feb 6, 2020 were included. The primary outcomes were death and survival till March 5. Data of demographics, clinical features, comorbidities, laboratory tests and complications were collected and compared for different outcomes. Cox regression was performed for prognostic factors.339 patients with COVID-19 (aged 71±8 years,173 females (51%)) were enrolled, including 80 (23.6%) critical, 159 severe (46.9%) and 100 moderate (29.5%) cases. Common comorbidities were hypertension (40.8%), diabetes (16.0%) and cardiovascular disease (15.7%). Common symptoms included fever (92.0%), cough (53.0%), dyspnea (40.8%) and fatigue (39.9%). Lymphocytopenia was a common laboratory finding (63.2%). Common complications included bacterial infection (42.8%), liver enzyme abnormalities (28.7%) and acute respiratory distress syndrome (21.0%). Till Mar 5, 2020, 91 cases were discharged (26.8%), 183 cases stayed in hospital (54.0%) and 65 cases (19.2%) were dead. Shorter length of stay was found for the dead compared with the survivors (5 (3-8) vs. 28 (26-29), P < 0.001). Symptoms of dyspnea (HR 2.35, P = 0.001), comorbidities including cardiovascular disease (HR 1.86, P = 0.031) and chronic obstructive pulmonary disease (HR 2.24, P = 0.023), and acute respiratory distress syndrome (HR 29.33, P < 0.001) were strong predictors of death. And a high level of lymphocytes was predictive of better outcome (HR 0.10, P < 0.001).High proportion of severe to critical cases and high fatality rate were observed in the elderly COVID-19 patients. Rapid disease progress was noted in the dead with a median survival time of 5 days after admission. Dyspnea, lymphocytopenia, comorbidities including cardiovascular disease and chronic obstructive pulmonary disease, and acute respiratory distress syndrome were predictive of poor outcome. Close monitoring and timely treatment should be performed for the elderly patients at high risk.
Could the Quick Sequential Organ Failure Assessment Predictive Accuracy Be Affected by Site of Infection?
Authors: Karolina Akinosoglou, Anne-Lise deLastic, Vasiliki Niarou, Dimitrios Ziazias, Christos Davoulos, Martha Kolosaka, Foteini Kosmopoulou, Spyridoula Theodoraki, Christina-Panagiota Koutsouri, Charalambos Gogos
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

We read with interest the article by Machado and colleagues (1) concerning the evaluation of the quick Sequential Organ Failure Assessment (qSOFA) score as a screening tool for mortality in two cohorts in Brazil.The authors state that a qSOFA score >2 has low sensitivity for predicting death in patients with suspected infection and may miss patients who ultimately die.Taking into consideration the opportunity of these two large cohorts of patients, it would be interesting to explore whether the site of infection plays any role in this observation.As we have previously argued, qSOFA score is potentially biased by its very parameters, because they are affected by different sites of infection (2).qSOFA could perform adequately or overperform in cases in which the infection site could involve score parameters (e.g., respiratory tract infections [RTIs] and respiratory rate) but not in cases in which potential parameters are not included in the qSOFA score but in which the underlying inflammatory response could still be expressed otherwise and drive poor outcomes (e.g., thrombocytopenia and hyperbilirubinemia).For this reason, we performed a retrospective cohort study to evaluate qSOFA performance in the assessment of mortality, depending on site of infection.Patients admitted with signs of infection (RTI, urinary tract infection [UTI], gastrointestinal [GI] tract infection, hepatobiliary [HB] system infection, and primary bacteremia [PB]) in the medical ward of a tertiary university hospital between May 1, 2016, and May 1, 2018, were included in this study (ethics committee approval 96/15.04.16).Patient disease severity according to systemic inflammatory response syndrome (SIRS) and qSOFA score was calculated upon presentation; epidemiological parameters were recorded; and outcomes were followed for 28 days.Using IBM SPSS Statistics version 25 software (IBM Corp.), we performed receiver operating characteristic curve analysis to assess the performance of qSOFA scores >2 in predicting survival for different sites of infection.A total of 614 patients were finally included in this study, involving RTI (n = 132), UTI (n = 232), PB (n = 47), GI tract infection (n = 104), and HB system infection (n = 99).The mean age of the population was 63 years, and 48% were male.Ninety-eight percent of patients with PB fulfilled the SIRS criteria for sepsis, followed by 74%, 72%, 55%, and 50% of patients with UTI, HB system infection, RTI, and GI tract infection, respectively.
Autoimmune complications of immunotherapy: pathophysiology and management
Authors: Karmela K Chan, Anne R Bass
Journal: BMJ (2020)

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or its ligand, programmed cell death protein ligand 1 (PD-L1), and lead to immune activation in the tumor micro-environment. ICIs can induce durable treatment responses in patients with advanced cancers, but they are commonly associated with immune related adverse events (irAEs) such as rash, colitis, hepatitis, pneumonitis, and endocrine and musculoskeletal disorders. Almost all patients experience some form of irAE, but high grade irAEs occur in approximately half of those on combination therapy (eg, anti-CTLA-4 plus anti-PD-1), and up to one quarter receiving ICI monotherapy. Fatal irAEs occur in approximately 1.2% of patients on CTLA-4 blockade and 0.4% of patients receiving PD-1 or PD-L1 blockade, and case fatality rates are highest for myocarditis and myositis. IrAEs typically occur in the first three months after ICI initiation, but can occur as early as one day after the first dose to years after ICI initiation. The mainstay of treatment is with corticosteroids, but tumor necrosis factor inhibitors are commonly used for refractory irAEs. Although ICIs are generally discontinued when high grade irAEs occur, ICI discontinuation alone is rarely adequate to resolve irAEs. Consensus guidelines have been published to help guide management, but will likely be modified as our understanding of irAEs grows.
Bronchoalveolar lavage fluid lymphocytosis in chronic hypersensitivity pneumonitis: a systematic review and meta-analysis
Authors: Nicola Adderley, Christopher J. Humphreys, Hayley Barnes, Brett Ley, Zahra A. Premji, Kerri A. Johannson
Journal: European Respiratory Journal (2020)

The role of bronchoalveolar lavage fluid (BALF) lymphocyte percentage in diagnosing chronic hypersensitivity pneumonitis (CHP) is unclear. We conducted a systematic review and meta-analysis of bronchoalveolar lavage (BAL) lymphocyte percentage in the diagnosis of CHP.We searched Medline, Embase and the Cochrane Library from inception to August 2019. Individual patient data were obtained to test performance characteristics of BAL lymphocyte percentage at different thresholds. Random-effects models were used for pooled estimates, with comparisons made between CHP and non-CHP interstitial lung diseases (ILDs).Fifty-three studies were included in the systematic review and 42 in the meta-analysis. The pooled estimate for BAL lymphocyte percentage was 42.8% (95% CI 37.7-47.8, I2=95.3%) in CHP, 10.0% (95% CI 6.9-13.1, I2=91.2%) in idiopathic pulmonary fibrosis (IPF), 23.1% (95% CI 3.0-43.2, I2=85.2%) in non-IPF idiopathic interstitial pneumonia (IIP), 23.4% (95% CI 11.0-35.9, I2=45.7%) in connective-tissue disease associated ILD (CTD-ILD) and 31.2% (95% CI 17.6-44.8, I2=95.2%) in sarcoidosis. Results differed between CHP and IPF (p<0.0001), non-IPF IIP (p=0.0309) or CTD-ILD (p=0.0824), but not between CHP and sarcoidosis (p=0.0966). Using individual patient data from eight studies, a lymphocyte percentage threshold of >20% provided a sensitivity of 68.1% and a specificity of 64.8% for CHP. Higher thresholds provided lower sensitivity with higher specificity. Older age and ever having smoked were associated with lower lymphocyte percentage in CHP.BAL lymphocyte percentage is higher in CHP compared to IPF and other IIPs, with higher thresholds providing improved specificity at the cost of sensitivity. However, the parent studies are at risk of incorporation bias and prospective studies should evaluate the additive discriminate value of BAL lymphocyte percentage to accurately diagnose CHP.
A phase II, multicenter, single-arm trial of eribulin as first or second line chemotherapy for HER2-negative advanced or metastatic breast cancer: Evaluation of efficacy, safety, and patient-reported outcomes.
Authors: Mitsuhiko Iwamoto, Kosei Kimura, Satoru Tanaka, Daigo Yamamoto, Katsuhide Yoshidome, Hiroyuki Ogura, Risa Terasawa, Nobuki Matsunami, Yuko Takahashi, Toshikatsu Nitta, Takashi Morimoto, Hiroya Fujioka, Kanako Kawaguchi, Kazuhisa Uchiyama
Journal: Journal of Clinical Oncology (2018)

e13059 Background: Although eribulin is a suitable option for early-line treatment of metastatic breast cancer (MBC), data on first- or second-line use of eribulin for human epidermal growth factor receptor 2 (HER2)-negative MBC are still limited. Therefore, we conducted a phase II trial to investigate the efficacy and safety of eribulin for first- or second-line chemotherapy for HER2-negative MBC. Methods: We performed a phase II, open-label, single-arm, multicenter study in Japan. Eligible patients were women with histologically confirmed HER2-negative MBC without chemotherapy or only one chemotherapy session for MBC. The primary endpoint was the overall response rate (ORR) and the secondary endpoints included the clinical benefit rate, progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and health-related quality of life (HRQoL). Results: A total of 35 patients with HER2-negative MBC were enrolled between March 2013 and February 2017 (data cut-off: July 31, 2017). The ORR was 37.1% (95% CI 21.1%–53.2%). The clinical benefit rate was 54.3% (95% CI 37.8%–70.8%). The median PFS was 6.2 months (95% CI 2.7–9.4 months) and median OS was 21.4 months (95% CI 11.5–32.9 months). Common grade 3/4 adverse events were neutropenia (42.9%) and febrile neutropenia (2.9%). Although the majority of non-hematological adverse events were mild in severity, one patient died of pneumonitis. In HRQoL analysis, eribulin appeared to maintain HRQoL of almost all the patients. Conclusions: Eribulin as first- or second-line chemotherapy is effective and has manageable tolerability for patients with HER2-negative MBC. Clinical trial information: UMIN000009568.
Assessment of Neonatal Circumcision Availability at Chicago-Area Hospitals
Authors: Ketan Jain-Poster, Ilina Rosoklija, Mateo Zambrano Navia, Max Maizels, Jane L. Holl, Matthew M. Davis, Emilie K. Johnson
Journal: JAMA Network Open (2020)

This survey study assesses possible barriers to neonatal male circumcision by evaluating circumcision-related requirements and procedures among 44 birthing hospitals in the Chicago area in Illinois.
Relationship of a Claims-Based Frailty Index to Annualized Medicare Costs
Authors: Kenton J. Johnston, Hefei Wen, Karen E. Joynt Maddox
Journal: Annals of Internal Medicine (2020)

Medicare uses the Centers for Medicare & Medicaid Services Hierarchical Condition Category (CMS-HCC) model to predict patients' annualized Medicare costs in value-based payment programs. The CMS-HCC model does not include measures of frailty, and prior research shows that it systematically underpredicts costs for frail Medicare beneficiaries.To determine whether a claims-based frailty index can improve Medicare cost prediction.Retrospective cohort study.Medicare Current Beneficiary Survey linked to Medicare claims, 2006 to 2013.16 535 community-dwelling, fee-for-service beneficiaries representing 26 705 patient-years.Patient frailty status was classified using a validated claims-based frailty index. The association between the frailty index and annualized Medicare costs was examined, and regression methods were used to compare observed Medicare costs versus predictions based on the standard CMS-HCC model with and without the frailty index.Mean costs were $5724 for the 8910 patients classified as robust (46.4% of patient-years), $12 462 for the 8405 prefrail patients (41.6%), $26 239 for the 2215 mildly frail patients (9.6%), and $44 586 for the 593 patients classified as moderately to severely frail (2.5%). The frailty index addition to the CMS-HCC model predicted on average an additional $2712, $7915, and $16 449 in costs for prefrail, mildly frail, and moderately to severely frail patients, respectively, beyond the CMS-HCC model alone. On average, the model with the frailty index addition resulted in more accurate predictions of costs for patients at all 4 levels of frailty. However, observed costs remained more widely distributed than predictions from the enhanced model at all levels of frailty.The claims-based index is a proxy for frailty and is likely less accurate than an in-person examination.The CMS-HCC model with the frailty index addition is an improvement over current Medicare cost prediction.None.
Early consensus management for non-ICU acute respiratory failure SARS-CoV-2 emergency in Italy: from ward to trenches
Authors: Michele Vitacca, Stefano Nava, Pierachille Santus, Sergio Harari
Journal: European Respiratory Journal (2020)

<b>The development, as soon as possible, of a European respiratory specialist network is mandatory to manage the unexpected emergency of SARS-CoV-2; the ERS has a key role to play in urgently providing recommendations, guidelines, support and information</b>https://bit.ly/39OaH0o