tbuckley/cabot-search huggingface dataset:
Assessment of immunity to polio among Rohingya children in Cox’s Bazar, Bangladesh, 2018: A cross-sectional survey
Authors: Concepcion F. Estivariz, Sarah D. Bennett, Jacquelyn S. Lickness, Leora R. Feldstein, William C. Weldon, Eva Leidman, Daniel C. Ehlman, Muhammad F. H. Khan, Jucy M. Adhikari, Mainul Hasan, Mallick M. Billah, M. Steven Oberste, A. S. M. Alamgir, Meerjady D. Flora
Journal: PLoS Medicine (2020)

We performed a cross-sectional survey in April-May 2018 among Rohingya in Cox's Bazar, Bangladesh, to assess polio immunity and inform vaccination strategies.Rohingya children aged 1-6 years (younger group) and 7-14 years (older group) were selected using multi-stage cluster sampling in makeshift settlements and simple random sampling in Nayapara registered camp. Surveyors asked parents/caregivers if the child received any oral poliovirus vaccine (OPV) in Myanmar and, for younger children, if the child received vaccine in any of the 5 campaigns delivering bivalent OPV (serotypes 1 and 3) conducted during September 2017-April 2018 in Cox's Bazar. Dried blood spot (DBS) specimens were tested for neutralizing antibodies to poliovirus types 1, 2, and 3 in 580 younger and 297 older children. Titers ≥ 1:8 were considered protective. Among 632 children (335 aged 1-6 years, 297 aged 7-14 years) enrolled in the study in makeshift settlements, 51% were male and 89% had arrived after August 9, 2017. Among 245 children (all aged 1-6 years) enrolled in the study in Nayapara, 54% were male and 10% had arrived after August 9, 2017. Among younger children, 74% in makeshift settlements and 92% in Nayapara received >3 bivalent OPV doses in campaigns. Type 1 seroprevalence was 85% (95% CI 80%-89%) among younger children and 91% (95% CI 86%-95%) among older children in makeshift settlements, and 92% (88%-95%) among younger children in Nayapara. Type 2 seroprevalence was lower among younger children than older children in makeshift settlements (74% [95% CI 68%-79%] versus 97% [95% CI 94%-99%], p < 0.001), and was 69% (95% CI 63%-74%) among younger children in Nayapara. Type 3 seroprevalence was below 75% for both age groups and areas. The limitations of this study are unknown routine immunization history and poor retention of vaccination cards.Younger Rohingya children had immunity gaps to all 3 polio serotypes and should be targeted by future campaigns and catch-up routine immunization. DBS collection can enhance the reliability of assessments of outbreak risk and vaccination strategy impact in emergency settings.
CA-125 ELIMination Rate Constant K (KELIM) Is a Marker of Chemosensitivity in Patients with Ovarian Cancer: Results from the Phase II CHIVA Trial
Authors: Benoit You, Patrick Robelin, Michel Tod, Christophe Louvet, Jean-Pierre Lotz, Sophie Abadie-Lacourtoisie, Michel Fabbro, Christophe Desauw, Nathalie Bonichon-Lamichhane, Jean-Emmanuel Kurtz, Philippe Follana, Marianne Leheurteur, Francesco Del Piano, Gwénael Ferron, Gaëtan De Rauglaudre, Isabelle Ray-Coquard, Pierre Combe, Annick Chevalier-Place, Florence Joly, Alexandra Leary, Eric Pujade-Lauraine, Gilles Freyer, Olivier Colomban
Journal: Clinical Cancer Research (2020)

In patients with ovarian cancer receiving neoadjuvant chemotherapy, the first-line treatment success will depend on both the tumor-primary chemosensitivity and the completeness of interval debulking surgery (IDS). The modeled CA-125 ELIMination rate constant K (KELIM), calculated with the CA-125 longitudinal kinetics during the first 100 chemotherapy days, is a validated early marker of tumor chemosensitivity. The objective was to investigate the role of the chemosensitivity relative to the success of first-line medical-surgical treatment.The CA-125 concentrations were prospectively measured in the randomized phase II trial CHIVA (NCT01583322, carboplatin-paclitaxel regimen ± nintedanib, and IDS, n = 188 patients). The KELIM predictive value regarding the tumor response rate, likelihood of complete IDS, risk of subsequent platinum-resistant relapse (PtRR), progression-free survival (PFS), and overall survival (OS) was assessed using univariate and multivariate tests.The data from 134 patients were analyzed. KELIM was an independent and major predictor of subsequent PtRR risk, and of survivals. The final logistic regression model, including KELIM [OR = 0.13; 95% confidence interval (CI), 0.03-0.49] and complete IDS (no vs. yes, OR = 0.30; 95% CI, 0.11-0.76) highlights the preponderant role of chemosensitivity on the success of the first-line treatment. In patients with highly chemosensitive diseases, the patient prognosis was driven more by the chemotherapy-induced antitumor effects than by the surgery.The tumor-primary chemosensitivity, assessed by the modeled CA-125 KELIM calculated during neoadjuvant chemotherapy (http://www.biomarker-kinetics.org/CA-125-neo), may be a major parameter to consider for decision-making regarding IDS attempt, and selecting patients for treatments meant to reverse the primary chemoresistance.See related commentary by May and Oza, p. 4432.
Hippocampal radiotherapy dose constraints for predicting long-term neurocognitive outcomes: mature data from a prospective trial in young patients with brain tumors
Authors: Jayant S Goda, Debnarayan Dutta, Uday Krishna, Savita Goswami, Vikas Kothavade, Sadhna Kannan, Madan Maitre, Nazia Bano, Tejpal Gupta, Rakesh Jalali
Journal: Neuro-Oncology (2020)

Hippocampus is considered to be the seat for neurocognitive functions. Avoidance of hippocampus during radiotherapy to brain may serve to preserve various domains of neurocognition. We aimed to derive radiotherapy dose constraints to hippocampi for preserving neurocognition in young patients with brain tumors by measuring various neurocognitive parameters.
Loss of Apc Rapidly Impairs DNA Methylation Programs and Cell Fate Decisions in Lgr5+ Intestinal Stem Cells
Authors: Marco Bruschi, Laure Garnier, Elouan Cleroux, Alicia Giordano, Michael Dumas, Anaïs F. Bardet, Thomas Kergrohen, Stanislas Quesada, Pierre Cesses, Michael Weber, François Gerbe, Philippe Jay
Journal: Cancer Research (2020)

Colorectal cancer initiation and progression result from the accumulation of genetic and epigenetic alterations. Although aberrant gene expression and DNA methylation profiles are considered hallmarks of colorectal cancer development, the precise timing at which these are produced during tumor establishment remains elusive. Here we investigated the early transcriptional and epigenetic changes induced by adenomatous polyposis coli (Apc) inactivation in intestinal crypts. Hyperactivation of the Wnt pathway via Apc inactivation in crypt base columnar intestinal stem cells (ISC) led to their rapid accumulation driven by an impaired molecular commitment to differentiation, which was associated with discrete alterations in DNA methylation. Importantly, inhibiting the enzymes responsible for de novo DNA methylation restored the responsiveness of Apc-deficient intestinal organoids to stimuli regulating the proliferation-to-differentiation transition in ISC. This work reveals that early DNA methylation changes play critical roles in the establishment of the impaired fate decision program consecutive to Apc loss of function. SIGNIFICANCE: This study demonstrates the functional impact of changes in DNA methylation to determine the colorectal cancer cell phenotype following loss of Apc function.
Abstract I21: Understanding metabolic limitations in pancreatic cancer
Authors: Matthew G. Vander Heiden
Journal: Cancer Research (2019)

Abstract Complex regulatory mechanisms enable cell metabolism to match physiologic state. The major pathways cells use to turn nutrients into energy and to synthesize macromolecules have been elucidated; however, there remain many unanswered questions regarding how metabolism supports cancer cell proliferation and thus how best to target metabolism for pancreatic cancer treatment. Of note, some therapies for pancreas cancer target metabolic processes that are thought to be essential in all cells. This raises a key question of how drugs that target otherwise essential processes like nucleotide metabolism show differential effectiveness to treat cancers. We have characterized the factors that drive sensitivity to disruption of specific metabolic processes, including nucleotide metabolism, and find that both cancer cell extrinsic and intrinsic factors dictate metabolic vulnerabilities. Further, this leads to different cells being more reliant on limiting nutrients for different metabolic processes, creating a framework to understand how specific cancer cells becomes sensitive to agents that target otherwise essential pathways. Citation Format: Matthew G. Vander Heiden. Understanding metabolic limitations in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I21.
Echocardiographic Pulmonary Hypertension and Right Heart Function—The Big Picture
Authors: Muddassir Mehmood
Journal: JAMA Cardiology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Indications for healthcare surge capacity in European countries facing an exponential increase in coronavirus disease (COVID-19) cases, March 2020
Authors: Frederik Verelst, Elise Kuylen, Philippe Beutels
Journal: Eurosurveillance (2020)

European healthcare systems face extreme pressure from coronavirus disease (COVID-19). We relate country-specific accumulated COVID-19 deaths (intensity approach) and active COVID-19 cases (magnitude approach) to measures of healthcare system capacity: hospital beds, healthcare workers and healthcare expenditure. Modelled by the intensity approach with a composite measure for healthcare capacity, the countries experiencing the highest pressure on 25 March 2020 - relative to Italy on 11 March - were Italy, Spain, the Netherlands and France (www.covid-hcpressure.org).
A Critical Role for Estrogen-Related Receptor Signaling in Cardiac Maturation
Authors: Tomoya Sakamoto, Timothy R. Matsuura, Shibiao Wan, David M. Ryba, J`unil Kim, Kyoung Jae Won, Ling Lai, Christopher Petucci, Nataliya Petrenko, Kiran Musunuru, Rick B. Vega, Daniel P. Kelly
Journal: Circulation Research (2020)

The heart undergoes dramatic developmental changes during the prenatal to postnatal transition, including maturation of cardiac myocyte energy metabolic and contractile machinery. Delineation of the mechanisms involved in cardiac postnatal development could provide new insight into the fetal shifts that occur in the diseased heart and unveil strategies for driving maturation of stem cell-derived cardiac myocytes.To delineate transcriptional drivers of cardiac maturation.We hypothesized that ERR (estrogen-related receptor) α and γ, known transcriptional regulators of postnatal mitochondrial biogenesis and function, serve a role in the broader cardiac maturation program. We devised a strategy to knockdown the expression of ERRα and γ in heart after birth (pn-csERRα/γ [postnatal cardiac-specific ERRα/γ]) in mice. With high levels of knockdown, pn-csERRα/γ knockdown mice exhibited cardiomyopathy with an arrest in mitochondrial maturation. RNA sequence analysis of pn-csERRα/γ knockdown hearts at 5 weeks of age combined with chromatin immunoprecipitation with deep sequencing and functional characterization conducted in human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CM) demonstrated that ERRγ activates transcription of genes involved in virtually all aspects of postnatal developmental maturation, including mitochondrial energy transduction, contractile function, and ion transport. In addition, ERRγ was found to suppress genes involved in fibroblast activation in hearts of pn-csERRα/γ knockdown mice. Disruption of Esrra and Esrrg in mice during fetal development resulted in perinatal lethality associated with structural and genomic evidence of an arrest in cardiac maturation, including persistent expression of early developmental and noncardiac lineage gene markers including cardiac fibroblast signatures. Lastly, targeted deletion of ESRRA and ESRRG in hiPSC-CM derepressed expression of early (transcription factor 21 or TCF21) and mature (periostin, collagen type III) fibroblast gene signatures.ERRα and γ are critical regulators of cardiac myocyte maturation, serving as transcriptional activators of adult cardiac metabolic and structural genes, an.d suppressors of noncardiac lineages including fibroblast determination.
Abstract P3-06-15: Identifying genomic alterations in stage IV breast cancer patients using MammaSeq: An international collaborative study
Authors: Atilla Soran, Mustafa Sahin, Serdar Ugras, Esin Celik, Osama Shiraz Shah, Peter C Lucas, Adrian V Lee
Journal: Cancer Research (2020)

Abstract Background: Identification of genomic alterations present in cancer patients can aid in improving cancer diagnosis and prognosis. In this study, we aimed to identify clinically actionable variations present in stage IV breast cancer (BC) samples. Methods: DNA was extracted from formalin fixed paraffin embedded samples of breast cancer (n=41). DNA was sequenced using MammaSeqTM, a breast cancer specific NGS panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data. Resulting single nucleotide variants (SNVs) were annotated using CRAVAT toolkit. CNVkit was employed to identify copy number variations (CNVs). The PMKB and OncoKB Precision Oncology Databases were used to associate clinical significance with the identified variants. Results: A total of 41 BC patient samples were sequenced (read depth of 94 - 13340, median of 1529). In total, 96 different alterations (84 SNVs and 12 CNVs) were identified. Frequent SNVs were seen in PIK3CA, TP53, IKBKE, ATM and MAP3K1 genes. Moreover, amplifications were found in ERBB2, FGFR and AR, and deletions in BRCA2, RUNX1 and RB1. 3 CNVs (ERRB2, FGFR and AR amplifications) and 7 SNVs (IDH1.R132H, TP53.E204*, AKT1.E17K, PI3KCA.E545K, PI3KCA.H1047R, PI3KCA.R88Q and ERBB2.V777L) were reported as clinically significant by PMKB and OncoKB. Conclusion: We identified 96 alterations in 50 genes in 41 stage IV BC tissue samples using MammaSeqTM. Ten of these alterations were reported as clinically significant. This study highlights the potential use of cancer specific NGS panels in clinic to get better insight into the cancer patient-specific genomic alterations. Citation Format: Atilla Soran, Mustafa Sahin, Serdar Ugras, Esin Celik, Osama Shiraz Shah, Peter C Lucas, Adrian V Lee. Identifying genomic alterations in stage IV breast cancer patients using MammaSeq: An international collaborative study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-06-15.
Medicine: before COVID-19, and after
Authors: Margaret McCartney
Journal: The Lancet (2020)

It was a simmering that has caught fire. When, earlier this year, it became obvious that coronavirus disease 2019 (COVID-19) was a virus capable of pandemic damage and global reach, I wondered whether we were looking into the abyss. But my work in general practice was busy with so many seemingly more important things, and I looked away.
Abstract 14054: The QT Interval During Early Infancy Lengthens by Environmental Tobacco Smoke Exposure
Authors: Kenji Harada, Yukiko Harada, Manatomo Toyono
Journal: Circulation (2017)

Background: Environmental tobacco smoke (ETS) exposure is associated with increased risk for sudden infant death syndrome (SIDS). The association between long QT interval and SIDS has been clearly ...
Covid-19: Lack of PPE in care homes is risking spread of virus, leaders warn
Authors: Gareth Iacobucci
Journal: BMJ (2020)

A lack of access to personal protective equipment (PPE) and staff testing in care homes poses a major risk of covid-19 being spread, sector leaders have warned. Care homes have been identified as one of the biggest potential risks for virus spreading, owing to the number of elderly residents with underlying health conditions. 

At a health select committee hearing hosted remotely on 26 March, Sarah Pickup, the deputy chief executive of the Local Government Association, said that more equipment and testing was needed to protect both residents and workers.1 “Access to PPE is insufficient in the care sector,” she said, warning that people entering care homes on discharge from hospital could …
David Oliver: Covid-19—recriminations and political point scoring must wait
Authors: David Oliver
Journal: BMJ (2020)

Now is surely not the time for premature post mortems on our response to covid-19, for party political point scoring, or for reheating of historical resentments. Nor is it the time for attacks on officials and managers trying to solve problems as best they can.

In the war on the global covid-19 pandemic, responses in the NHS and wider public policy are changing at a pace more like time lapse photography than our usual peacetime decision and communications cycle.

The virus threatens our health and will hospitalise or kill many. The repurposing of health services to deal with it will marginalise many people with other important, life limiting needs. For months, it will transform the jobs of people in frontline healthcare and other key public services. It will leave millions of self-employed, contract, or salaried workers in a whole range of industries with serious financial problems and will devastate many sectors.

Beyond national boundaries, governments of every …
Re-exploration with in 30-days after living donor liver transplantation: Single centre experience
Authors: Apurv Deshpande, Ashish Singhal, Kausar Makki, Furqan Ahmed, Mohd Qaleem, Arif Khan, Vishal Chorasiya, Ajitabh Srivastava, Vivek Vij
Journal: International Journal of Surgery (2020)
Immunosuppressant indulges EBV reactivation and related lymphoproliferative disease by inhibiting Vδ2<sup>+</sup>T cells activities after hematopoietic transplantation for blood malignancies
Authors: Jiangying Liu, Haitao Gao, Lan-Ping Xu, Xiao-Dong Mo, Ruoyang Liu, Shuang Liang, Ning Wu, Ming Wang, Zhidong Wang, Ying-Jun Chang, Yu Wang, Xiao-Hui Zhang, Xiao-Jun Huang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Following the extensive use of immunosuppressive drugs in the clinic, immunosuppression-associated side effects have received increasing attention. Epstein-Barr virus (EBV) reactivation and related lymphoproliferative diseases (LPD) are the lethal complications observed after allogeneic hematopoietic cell transplantation (alloHCT). While studies generally suggest an association between immunosuppressants and EBV reactivation, the effects of specific immunosuppressive drugs and which T-cell subsets mediate these correlations are unclear. Vδ2 + T cells are correlated with EBV reactivation after alloHCT. Researchers have not determined whether Vδ2 + T-cell activities are affected by immunosuppressants and thereby facilitate EBV reactivation and related LPD. Methods A clinical cohort study of 170 patients with hematopoietic malignancies who received haploidentical hematopoietic cell transplantation (haploHCT) was performed to investigate whether the early cessation of mycophenolate mofetil (MMF) decreases EBV reactivation and related LPD and to determine whether this change is associated with the recovery of Vδ2 + T cells after transplantation. The effects of MMF on the expansion and anti-EBV capacity of Vδ2 + T cells were detected in vitro and in an immunodeficient mouse model. Results A reduction in the course of MMF significantly improved the recovery of Vδ2 + T cells from 30 to 90 days after haploHCT (p=0.002, p=0.042 and p=0.035, respectively), accompanied by a significant decrease in EBV reactivation (from 26% to 13%, p=0.033) and EBV-LPD (from 10.6% to 2.4%, p=0.029). The day-30 Vδ2 + T level remained an independent factor for EBV reactivation in patients with different MMF durations (p=0.007). In the in-vitro experiments, MMF inhibited Vδ2 + T-cell expansion and its cytotoxicity on EBV-transformed malignant cells. Furthermore, the therapeutic and prophylactic effects of adoptively transferred human Vδ2 + T cells were attenuated by the MMF treatment in immunodeficient mice with EBV-LPD. Conclusions These results elucidated a negative effect of immunosuppressants on the anti-EBV capacity of Vδ2 + T cells. Strategies that appropriately relieve the immunosuppression may improve anti-EBV immunity by increasing the activity of Vδ2 + T cells after alloHCT.
Should All Donors Be Treated by Ex Vivo Lung Perfusion?
Authors: Dong Tian, Yu Wang, Shi-Yang Deng
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Rapid assessment of regional SARS-CoV-2 community transmission through a convenience sample of healthcare workers, the Netherlands, March 2020
Authors: Chantal B Reusken, Anton Buiting, Chantal Bleeker-Rovers, Bram Diederen, Mariëtte Hooiveld, Ingrid Friesema, Marion Koopmans, Titia Kortbeek, Suzanne PM Lutgens, Adam Meijer, Jean-Luc Murk, Ilse Overdevest, Thera Trienekens, Aura Timen, Wouter Van den Bijllaardt, Jaap Van Dissel, Arianne Van Gageldonk-Lafeber, Dewi Van der Vegt, Peter C Wever, Wim Van der Hoek, Jan Kluytmans
Journal: Eurosurveillance (2020)

To rapidly assess possible community transmission in Noord-Brabant, the Netherlands, healthcare workers (HCW) with mild respiratory complaints and without epidemiological link (contact with confirmed case or visited areas with active circulation) were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within 2 days, 1,097 HCW in nine hospitals were tested; 45 (4.1%) were positive. Of six hospitals with positive HCW, two accounted for 38 positive HCW. The results informed local and national risk management.