tbuckley/cabot-search huggingface dataset:
Exposure, hazard, and vulnerability and their contribution to Schistosoma haematobium re-infection in northern Senegal
Authors: Andrea J Lund, Susanne H Sokolow, Isabel J Jones, Chelsea L Wood, Sofia Ali, Andrew Chamberlin, Alioune Badara Sy, M Moustapha Sam, Nicolas Jouanard, Anne-Marie Schacht, Simon Senghor, Assane Fall, Raphael Ndione, Gilles Riveau, Giulio A De Leo, David Lopez-Carr
Journal: The Lancet Planetary Health (2021)

BackgroundThe risk of infectious diseases, including snail-borne schistosomiasis, is determined by three inter-related components: exposure, hazard, and vulnerability. For schistosomiasis, exposure occurs through behaviours involving water contact, but not without the environmental hazard of snails and parasites in the water. Socioeconomic vulnerability makes it difficult to reduce exposure in the presence of hazard, because it increases reliance on hazardous activities and environments. We aimed to quantify the contributions of exposure, hazard, and vulnerability to schistosome re-infection presence and intensity.MethodsWe used cross-sectional parasitological data from 821 school-aged children (5–15 years) in 13 villages along the Senegal River, survey data from 411 households where those children resided, and ecological data from all 24 village water contact sites. We fitted mixed-effects logistic and negative binomial regressions with indices of exposure, hazard, and vulnerability as explanatory variables of Schistosoma haematobium infection, along with demographic control variables. Multimodel inference was used to determine the relative importance of each component of risk and model averaging was used to quantify associations between infection outcomes and indices of hazard, exposure, and vulnerability.FindingsThe most important component of S haematobium presence was hazard (Σwi=0·95), followed by vulnerability (Σwi=0·91), and the most important component of S haematobium intensity was exposure (Σwi=1·00), followed by hazard (Σwi=0·76). Hazard was positively associated with infection presence (odds ratio [OR]=1·49, 95% CI 1·12–1·97), whereas exposure was positively associated with infection intensity.InterpretationOur findings highlight how social (exposure and vulnerability) and environmental (hazard) processes act together to facilitate the acquisition and accumulation of schistosome infection from the environment across time and space. This approach can inform targeting of social and environmental interventions as complements to mass drug administration.FundingNational Science Foundation Couple Natural Human Systems programme (1414102), Bill and Melinda Gates Foundation (OPP1114050), James and Nancy Kelso Fellowship through the Stanford Interdisciplinary Graduate Fellowship programme at Stanford University (AJL), Michigan Society of Fellows at the University of Michigan, a Sloan Research Fellowship from the Alfred P Sloan Foundation, a UW Innovation Award and a grant from the National Science Foundation (CLW; OCE-1829509).
Rothman Index As a Real-Time Predictor of Intensive Care Unit Admissions and Mortality in Acute Myeloid Leukemia Patients Undergoing Induction Chemotherapy
Authors: Deepa Gotur, Sai Ravi Kiran Pingali, Lawrence Rice, Ibrahim F. Ibrahim, Janice L Zimmerman, Stephen Wong, Christopher Jude Cortes, Mamta Puppala, Zheng Yin, Jasleen K. Randhawa, Swami P. Iyer
Journal: Blood (2017)
Midlands trust told to take urgent action over care of young people with mental health needs
Authors: Clare Dyer
Journal: BMJ (2021)

A hospital trust that is already at the centre of a large inquiry into maternity care has now been accused of failing to keep young people with mental health problems safe. 

The Care Quality Commission (CQC) has taken urgent action at Shrewsbury and Telford Hospital NHS Trust to ensure the safety of children and young people with mental health needs and learning disabilities.

Following a focused inspection at the Princess Royal Hospital in Telford, the CQC placed urgent conditions on the trust’s registration, banning it from …
Questions on <i>NOTCH2NLC</i> Repeat Expansions in Parkinson Disease
Authors: Wai Yan Yau, Henry Houlden, Jana Vandrovcova
Journal: JAMA Neurology (2021)

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 Neurology 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 Neurology journal
Interstitial lung disease increases susceptibility to and severity of COVID-19
Authors: Hyun Lee, Hayoung Choi, Bumhee Yang, Sun-Kyung Lee, Tai Sun Park, Dong Won Park, Ji-Yong Moon, Tae-Hyung Kim, Jang Won Sohn, Ho Joo Yoon, Sang-Heon Kim
Journal: European Respiratory Journal (2021)

Background There are limited data regarding the relationship between interstitial lung disease (ILD) and the natural course of COVID-19. In this study, we investigate whether patients with ILD are more susceptible to COVID-19 than those without ILD and evaluate the impact of ILD on disease severity in patients with COVID-19. Methods A nationwide cohort of patients with COVID-19 (n=8070) and a 1:15 age-, sex- and residential area-matched cohort (n=121 050) were constructed between 1 January 2020 and 30 May 2020 in Korea. We performed a nested case–control study to compare the proportions of patients with ILD between the COVID-19 cohort and the matched cohort. Using the COVID-19 cohort, we also evaluated the risk of severe COVID-19 in patients with ILD versus those without ILD. Results The proportion of patients with ILD was significantly higher in the COVID-19 cohort than in the matched cohort (0.8% versus 0.4%; p&lt;0.001). The odds of having ILD was significantly higher in the COVID-19 cohort than in the matched cohort (adjusted OR 2.02, 95% CI 1.54–2.61). Among patients in the COVID-19 cohort, patients with ILD were more likely to have severe COVID-19 than patients without ILD (47.8% versus 12.6%), including mortality (13.4% versus 2.8%) (all p&lt;0.001). The risk of severe COVID-19 was significantly higher in patients with ILD than in those without ILD (adjusted OR 2.23, 95% CI 1.24–4.01). Conclusion The risks of COVID-19 and severe presentation were significantly higher in patients with ILD than in those without ILD.
An α-2-macroglobulin insertion-deletion polymorphism in Alzheimer disease
Authors: Ekaterina A. Rogaeva, Smita Premkumar, Janet Grubber, Lutgarde Serneels, William K. Scott, Toshitaka Kawarai, Youqiang Song, De'Lisa M. Hill, Suzanne M. Abou-Donia, Eden R. Martin, Jeffrey J. Vance, Gang Yu, Antonio Orlacchio, York Pei, Masaki Nishimura, Agres Supala, Brenda Roberge, Ann M. Saunders, Allen D. Roses, Donald Schmechel, Alison Crane-Gatherum, Sandro Sorbi, Amalia Bruni, Gary W. Small, P. Michael Conneally, Jonathan L. Haines, Fred Van Leuven, Peter H. St. George-Hyslop, Lindsay A. Farrer, Margaret A. Pericak-Vance
Journal: Nature Genetics (1999)
Abstract PO-016: Changes in the expression levels of DNAJAs in triple negative breast cancer cells exposed to cytotoxic chemotherapy
Authors: Devon Freeny
Journal: Clinical Cancer Research (2021)

Abstract Triple Negative Breast Cancer (TBNC) lacking biological targets results in limited therapeutic options and leads to high mortality rates. The last therapy is Doxorubicin (Cytotoxic chemotherapeutic drug), an anti-tumor therapeutic alternative; which has bad side effects (cardiotoxicity), due to dose dependence, leading to drug resistance. There are three primary mechanisms of action for doxorubicin: Intercalation into DNA, which directly affects transcription and replication. Inhibition of topoisomerase II activity during the double-strand break, which prevents the binding portion of the ligation reaction that topoisomerase II catalyzes, by stabilizing the DNA-topoisomerase II alpha complex. Lastly, generating free radicals as it cycles between its quinone and semi-quinone structures during metabolic reactions, which generates reactive oxygen species. Research says heat shock proteins (HSPs) help to protect cells using heat-shock response. Several HSPs have been tested, with limited knowledge of HSP40s (DNAJAs). We will determine which DNAJA (1 to 4) assists in the survival response to doxorubicin by observing the domains and expression of the proteins being exposed to chemotherapy. The J domain has shown to be a critical area for increasing cell sensitivity while reducing cardiotoxicity. Expression levels were analyzed via RT-PCR and Western Blots, and relevant domains via COSMIC database. In conclusion the first step to reducing cardiotoxicity with chemotherapeutics is by modifying HSP40 functionality in human cancer cells, providing an alternative to hypersensitization to chemotherapy, allowing for lower dosage with less side effects. Citation Format: Devon Freeny. Changes in the expression levels of DNAJAs in triple negative breast cancer cells exposed to cytotoxic chemotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-016.
Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia
Authors: Yair Herishanu, Irit Avivi, Anat Aharon, Gabi Shefer, Shai Levi, Yotam Bronstein, Miguel Morales, Tomer Ziv, Yamit Shorer Arbel, Lydia Scarfò, Erel Joffe, Chava Perry, Paolo Ghia
Journal: Blood (2021)
Randomised trials at the level of the individual
Authors: Jay J H Park, Nathan Ford, Denis Xavier, Per Ashorn, Rebecca F Grais, Zulfiqar A Bhutta, Herman Goossens, Kristian Thorlund, Maria Eugenia Socias, Edward J Mills
Journal: The Lancet Global Health (2021)

In global health research, short-term, small-scale clinical trials with fixed, two-arm trial designs that generally do not allow for major changes throughout the trial are the most common study design. Building on the introductory paper of this Series, this paper discusses data-driven approaches to clinical trial research across several adaptive trial designs, as well as the master protocol framework that can help to harmonise clinical trial research efforts in global health research. We provide a general framework for more efficient trial research, and we discuss the importance of considering different study designs in the planning stage with statistical simulations. We conclude this second Series paper by discussing the methodological and operational complexity of adaptive trial designs and master protocols and the current funding challenges that could limit uptake of these approaches in global health research.
Prognostic impact of early tumor shrinkage and depth of response in patients with microsatellite instability-high metastatic colorectal cancer receiving immune checkpoint inhibitors
Authors: Giovanni Fucà, Francesca Corti, Margherita Ambrosini, Rossana Intini, Massimiliano Salati, Elisabetta Fenocchio, Paolo Manca, Chiara Manai, Francesca Daniel, Alessandra Raimondi, Federica Morano, Salvatore Corallo, Michele Prisciandaro, Andrea Spallanzani, Virginia Quarà, Carmen Belli, Marta Vaiani, Giuseppe Curigliano, Chiara Cremolini, Filippo De Braud, Maria Di Bartolomeo, Vittorina Zagonel, Sara Lonardi, Filippo Pietrantonio
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immune checkpoint inhibitors (ICIs) are the new standard of care in microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Since tumor response dynamic parameters already shown a strong association with survival outcomes in patients with mCRC treated with first-line therapy, we investigated the association of early tumor shrinkage (ETS) and depth of response (DoR) in patients with MSI-H/dMMR mCRC treated with ICIs. Methods This is a retrospective, multicenter, cohort study in patients with dMMR and/or MSI-high mCRC treated with ICIs (anti-PD-1/PD-L1 with or without anti-CTLA-4 agents) with measurable disease and at least one post-baseline radiological disease reassessment. The Kaplan-Meier method and Cox proportional-hazards regression models were used for survival analyses. A maximally selected statistics method in a Cox regression model for progression-free survival (PFS) was used to determine the optimal cut-offs for ETS and DoR. Results We included a total of 169 patients: 116 (68.6%) were treated with anti-PD-1 monotherapy, whereas 53 (31.4%) with anti-PD-1 plus anti-CTLA-4 agents. Patients with primary progressive disease (N=37, 21.9%), experienced an extremely poor overall survival (OS) and were evaluated separately. In patients with clinical benefit, we observed a significant association between ETS and DoR with both OS and PFS, and we identified a relative reduction of at least 1% as the optimal cut-off for ETS and a relative reduction of at least 50% as the optimal cut-off for DoR. Conclusions ETS and DoR are important prognostic factors in patients with MSI-high mCRC treated with ICIs that might be useful to design treatment intensification/deintensification strategies. A prospective validation of both is warranted.
Abstract 16767: Re-Engineered Heart Cells From a Patient With R58Q-MYL2 Shows Increased Heart Rate, Cellular Hypertrophy, and Reduced L-Type Calcium Currents
Authors: Wei Zhou, Dan Ye, Sybil Hrstka, J. Martijn Bos, David J Tester, Michael J Ackerman
Journal: Circulation (2017)

Background: Hypertrophic cardiomyopathy (HCM) is one of the most common, heritable cardiovascular diseases, characterized by unexplained left ventricular hypertrophy. The myosin regulatory light ch...
NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation
Authors: Alexandros Papachristodoulou, Antonio Rodriguez-Calero, Sukanya Panja, Elizabeth Margolskee, Renu K. Virk, Teresa A. Milner, Luis Pina Martina, Jaime Y. Kim, Matteo Di Bernardo, Alanna B. Williams, Elvis A. Maliza, Joseph M. Caputo, Christopher Haas, Vinson Wang, Guarionex Joel De Castro, Sven Wenske, Hanina Hibshoosh, James M. McKiernan, Michael M. Shen, Mark A. Rubin, Antonina Mitrofanova, Aditya Dutta, Cory Abate-Shen
Journal: Cancer Discovery (2021)

Mitochondria provide the first line of defense against the tumor-promoting effects of oxidative stress. Here we show that the prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from oxidative stress. Integrating analyses of genetically engineered mouse models, human prostate cancer cells, and human prostate cancer organotypic cultures, we find that, in response to oxidative stress, NKX3.1 is imported to mitochondria via the chaperone protein HSPA9, where it regulates transcription of mitochondrial-encoded electron transport chain (ETC) genes, thereby restoring oxidative phosphorylation and preventing cancer initiation. Germline polymorphisms of NKX3.1 associated with increased cancer risk fail to protect from oxidative stress or suppress tumorigenicity. Low expression levels of NKX3.1 combined with low expression of mitochondrial ETC genes are associated with adverse clinical outcome, whereas high levels of mitochondrial NKX3.1 protein are associated with favorable outcome. This work reveals an extranuclear role for NKX3.1 in suppression of prostate cancer by protecting mitochondrial function. SIGNIFICANCE: Our findings uncover a nonnuclear function for NKX3.1 that is a key mechanism for suppression of prostate cancer. Analyses of the expression levels and subcellular localization of NKX3.1 in patients at risk of cancer progression may improve risk assessment in a precision prevention paradigm, particularly for men undergoing active surveillance.See related commentary by Finch and Baena, p. 2132.This article is highlighted in the In This Issue feature, p. 2113.
G-CSF Vs Haematopoietic Stem Cell Transplantation in Severe Congenital Neutropenia with ELANE Mutation: Role of G-CSF Dose. a Retrospective Controlled Study on Behalf of Saawp (Severe Aplastic Anemia Working Party) of the EBMT, of the Stem Cell Transplant for Immunodeficiency Group in Europe (SCETIDE), of the Severe Chronic Neutropenia French Registry (SCNFR) and Italian Neutropenia Registry (INR)
Authors: Francesca Fioredda, Filomena Pierri, Sabrina Zanardi, Bobby Gaspar, Phil Ancliff, Marc Bierings, Gulyuz Ozturk, Owen Smith, Paul Veys, Per Ljungman, Regis Peffault De Latour, Reuven Or, Robert Wynn, Krzysztof Kalwak, Giovanna Russo, Fabio Tucci, Christine M. Knoll, Baldo Martire, Claudio Favre, Christine bellanne Chantelot, Blandine Beaupain, Jean Donadieu, Carlo Dufour
Journal: Blood (2017)
Eradication of large established tumors by drug-loaded bacterial particles via a neutrophil-mediated mechanism
Authors: Gaili Ji, Qiqi Li, Yuge Shen, Jia Gan, Lin Xu, Yuxi Wang, Hui Luo, Yun Yang, E. Dong, Guimin Zhang, Binrui Liu, Xiaozhu Yue, Wei Zhang, Hanshuo Yang
Journal: Journal of Controlled Release (2021)
Re: Cosimo De Nunzio, Benjamin Brucker, Thomas Bschleipfer, et al. Beyond Antimuscarinics: A Review of Pharmacological and Interventional Options for Overactive Bladder Management in Men. Eur Urol 2021;79:492–504
Authors: Satoshi Funada, Takashi Yoshioka, Yan Luo
Journal: European Urology (2021)
Abstract PO-052: Radiation regimen and timing of PD1 blockade critically influence response to combination therapy in head and neck squamous cell carcinoma
Authors: Aparajita Verma, Michael Habitzruther, Kristopher Attwood, Mukund Seshadri
Journal: Clinical Cancer Research (2021)

Abstract Head and neck squamous cell carcinoma (HNSCC) constitute the sixth most common cancer worldwide, with a 5-year survival of less than 50% for advanced HNSCC patients. Radiation therapy (RT) is widely used in the treatment of HNSCC patients. Preclinical studies have shown that RT can trigger immune mediated response that potentiates tumor regression. However, the use of RT in combination with immune checkpoint inhibitor, specifically programmed death protein-1 blockade (αPD-1), has not been extensively examined in HNSCC. In vitro studies in our laboratory revealed that radiation increased PD-L1 expression in HNSCC tumor cells in a dose-dependent manner. Based on this observation, we hypothesized that the efficacy of RT and αPD-1 therapy would be critically influenced by the timing of αPD-1 of administration. To test this hypothesis, we conducted a preclinical study using a novel orthotopic immunocompetent mouse model of HNSCC (RPMOC1). Tumor bearing mice were randomized into the following arms: RT (single dose 10 Gy), fractionated RT (fRT- 2Gy x 5), RT prior to αPD-1(200 μg), RT post αPD-1, fRT prior to αPD-1 and fRT post αPD-1. Non-invasive magnetic resonance imaging (MRI) was used to monitor tumor response to therapy. All treatment regimens were well tolerated and did not result in weight loss during the experiment. The most potent tumor growth inhibition was observed in the RT (10 Gy) and αPD-1 combination therapy group. RT given either before or after αPD-1 therapy resulted in a significant decrease in tumor volumes (p&amp;lt;0.05) compared to other groups. Combination therapy with fractionated radiation did not show improved response compared to monotherapy. Overall, our observations indicate that tumor response to combined radiation and immunotherapy is critically influenced by the radiation regimen and timing of PD1 blockade in HNSCC. Citation Format: Aparajita Verma, Michael Habitzruther, Kristopher Attwood, Mukund Seshadri. Radiation regimen and timing of PD1 blockade critically influence response to combination therapy in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-052.
Fast, cell-resolution, contiguous-wide two-photon imaging to reveal functional network architectures across multi-modal cortical areas
Authors: Keisuke Ota, Yasuhiro Oisi, Takayuki Suzuki, Muneki Ikeda, Yoshiki Ito, Tsubasa Ito, Hiroyuki Uwamori, Kenta Kobayashi, Midori Kobayashi, Maya Odagawa, Chie Matsubara, Yoshinori Kuroiwa, Masaru Horikoshi, Junya Matsushita, Hiroyuki Hioki, Masamichi Ohkura, Junichi Nakai, Masafumi Oizumi, Atsushi Miyawaki, Toru Aonishi, Takahiro Ode, Masanori Murayama
Journal: Neuron (2021)
Invest to staff the NHS properly, healthcare leaders warn prime minister
Authors: Abi Rimmer
Journal: BMJ (2021)

In a joint letter to the prime minister, healthcare leaders have called for a plan, matched by investment, to tackle NHS staff shortages in the medium and long term.

The NHS Confederation, NHS Providers, the British Medical Association, the Royal College of Nursing, the Academy of Royal Medical Colleges, and Unison warned that, without such a plan, vacancies would pose a huge risk to the retention of existing staff.1

Danny Mortimer, chief executive of the NHS Confederation, said that the government desperately needed to …
Global Phosphoproteomics Reveal CDK Suppression as a Vulnerability to KRas Addiction in Pancreatic Cancer
Authors: Aslamuzzaman Kazi, Liwei Chen, Shengyan Xiang, Rajanikanth Vangipurapu, Hua Yang, Francisca Beato, Bin Fang, Terence M. Williams, Kazim Husain, Patrick Underwood, Jason B. Fleming, Mokenge Malafa, Eric A. Welsh, John Koomen, José Trevino, Saïd M. Sebti
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Among human cancers that harbor mutant (mt) KRas, some, but not all, are dependent on mt KRas. However, little is known about what drives KRas dependency. Experimental Design: Global phosphoproteomics, screening of a chemical library of FDA drugs, and genome-wide CRISPR/Cas9 viability database analysis were used to identify vulnerabilities of KRas dependency. Results: Global phosphoproteomics revealed that KRas dependency is driven by a cyclin-dependent kinase (CDK) network. CRISPR/Cas9 viability database analysis revealed that, in mt KRas-driven pancreatic cancer cells, knocking out the cell-cycle regulators CDK1 or CDK2 or the transcriptional regulators CDK7 or CDK9 was as effective as knocking out KRas. Furthermore, screening of a library of FDA drugs identified AT7519, a CDK1, 2, 7, and 9 inhibitor, as a potent inducer of apoptosis in mt KRas-dependent, but not in mt KRas-independent, human cancer cells. In vivo AT7519 inhibited the phosphorylation of CDK1, 2, 7, and 9 substrates and suppressed growth of xenografts from 5 patients with pancreatic cancer. AT7519 also abrogated mt KRas and mt p53 primary and metastatic pancreatic cancer in three-dimensional (3D) organoids from 2 patients, 3D cocultures from 8 patients, and mouse 3D organoids from pancreatic intraepithelial neoplasia, primary, and metastatic tumors. Conclusions: A link between CDK hyperactivation and mt KRas dependency was uncovered and pharmacologically exploited to abrogate mt KRas-driven pancreatic cancer in highly relevant models, warranting clinical investigations of AT7519 in patients with pancreatic cancer.