tbuckley/cabot-search huggingface dataset:
Occupational exposures and IPF: when the dust unsettles
Authors: Cathryn T Lee, Kerri A Johannson
Journal: Thorax (2020)

<b>Objective:</b> To compare injury case fatality rates in the United States (US) with New Zealand (NZ) to guide future information collection, research, and evaluation. <b>Design:</b> Using NZ (1992–96) and US (1996–98) mortality censuses, NZ national 1992–96 hospital discharge censuses, and US 1996–98 National Hospital Discharge Survey data, the authors compared case fatality rates by mechanism and intent of injury and age group. The analysis was restricted to severe injuries (AIS⩾3). <b>Subjects:</b> NZ (1992–96) and US (1996–98) populations. <b>Main outcome measures:</b> Ratio of case fatality rates in NZ versus the US (RCFR<sub>(NZ:US)</sub>). <b>Results:</b> Overall, among cases meeting the study criteria, unintentional injuries were 1.57 times more likely fatal in NZ and intentional assault injuries were 1.14 times more likely to be fatal in the US. Firearms were involved in 50% of US assaults versus 8% of NZ assaults. By mechanism, cutting/piercing injuries were 1.86, firearm injuries were 1.41, and motor vehicle injuries were 1.44 times more to be likely fatal in NZ. Natural/environmental injuries (RCFR<sub>NZ:US</sub> = 0.57), unintentional poisonings (RCFR<sub>NZ:US</sub> = 0.26), and unintentional suffocations (RCFR<sub>NZ:US</sub> = 0.67) were significantly more likely to be fatal in the US. <b>Conclusions:</b> Possible reasons for the observed results include: differences in geography and proportion of population in rural areas, trauma system differences, road design and vehicle types, seat belt use, larger role of firearms in US assaults, coding practices, policies, and environmental factors. Disparities evoke hypotheses to test in future research that will guide priority setting and intervention.
Tannic acid-functionalized boron nitride nanosheets for theranostics
Authors: Gayong Shim, Seungbeom Ko, Joo Yeon Park, Ju Han Suh, Quoc-Viet Le, Dongyoon Kim, Young Bong Kim, Geun Ho Im, Hun Nyun Kim, Yearn Seong Choe, Jihee Cho, Sanghee Kim, Yu-Kyoung Oh
Journal: Journal of Controlled Release (2020)
Clare Gerada: Doctors need dedicated space to reduce professional isolation
Authors: Clare Gerada
Journal: BMJ (2020)

Thursday 10 September is World Suicide Prevention Day. I will use it to remember doctors who have died by suicide, especially those connected with my service, NHS Practitioner Health. I will remember the consultant who, soon after receiving a letter telling him about a complaint, killed himself. Or the junior doctor who feared she would lose her job after making a prescribing error, so instead took her own life. As did the GP who fretted so much about his forthcoming appraisal that he lost perspective of what really mattered in his life and …
Nivolumab Plus Ipilimumab for Metastatic Castration-Resistant Prostate Cancer: Preliminary Analysis of Patients in the CheckMate 650 Trial
Authors: Padmanee Sharma, Russell K. Pachynski, Vivek Narayan, Aude Fléchon, Gwenaelle Gravis, Matthew D. Galsky, Hakim Mahammedi, Akash Patnaik, Sumit K. Subudhi, Marika Ciprotti, Burcin Simsek, Abdel Saci, Yanhua Hu, G. Celine Han, Karim Fizazi
Journal: Cancer Cell (2020)
Study Designs and Statistical Methods for Studies of Child and Adolescent Health Policies
Authors: Benjamin French, Elizabeth A. Stuart
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Effects of Acute and Chronic Graft-versus-myelodysplastic Syndrome on Long-term Outcomes Following Allogeneic Hematopoietic Cell Transplantation
Authors: Takaaki Konuma, Ken Ishiyama, Aiko Igarashi, Naoyuki Uchida, Yukiyasu Ozawa, Takahiro Fukuda, Yasunori Ueda, Ken-ichi Matsuoka, Takehiko Mori, Yuta Katayama, Makoto Onizuka, Tatsuo Ichinohe, Yoshiko Atsuta
Journal: Clinical Cancer Research (2020)

Potent graft-versus-tumor (GVT) effects associated with graft-versus-host disease (GVHD) might be dependent on hematologic disease type and status. However, the data regarding the impact of GVHD on transplant outcomes for patients with myelodysplastic syndrome (MDS) are limited.We retrospectively evaluated the impact of acute and chronic GVHD on transplant outcomes for a large cohort of adult patients with a low-risk (n = 1,193) and high-risk (n = 1,926) MDS treated by first allogeneic hematopoietic cell transplantation between 2001 and 2017.The multivariate analysis, in which development of GVHD was treated as a time-dependent covariate, showed that acute and chronic GVHD at any grade or severity did not improve overall mortality, relapse, or nonrelapse mortality (NRM) in low-risk MDS. For patients with high-risk MDS, development of limited chronic GVHD was significantly associated with lower overall mortality [HR, 0.66; 95% confidence interval (CI), 0.50-0.86; P = 0.002]. This is probably due to that the reduced risk of relapse with grade III-IV acute GVHD (HR, 0.41; 95% CI, 0.25-0.65; P = 0.0002), or limited (HR, 0.57; 95% CI, 0.39-0.83; P = 0.003) or extensive (HR, 0.56; 95% CI, 0.41-0.77; P = 0.0004) chronic GVHD was offset by increased NRM with grade III-IV acute GVHD or extensive chronic GVHD in high-risk MDS.These data demonstrated a survival benefit of the graft-versus-MDS effect is present only in high-risk MDS patients with limited chronic GVHD.See related commentary by Eckel and Deeg, p. 6404.
Self-crosslinkable chitosan-hyaluronic acid dialdehyde nanoparticles for CD44-targeted siRNA delivery to treat bladder cancer
Authors: Ye Liang, Yonghua Wang, Liping Wang, Zhijuan Liang, Dan Li, Xiaoyu Xu, Yuanbin Chen, Xuecheng Yang, Hongbo Zhang, Haitao Niu
Journal: Bioactive Materials (2020)

Bladder cancer is one of the concerning malignancies worldwide, which is lacking effective targeted therapy. Gene therapy is a potential approach for bladder cancer treatment. While, a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment
Development of a gene expression–based prognostic signature for <i>IDH</i> wild-type glioblastoma
Authors: Radia M Johnson, Heidi S Phillips, Carlos Bais, Cameron W Brennan, Timothy F Cloughesy, Anneleen Daemen, Ulrich Herrlinger, Robert B Jenkins, Albert Lai, Christoph Mancao, Michael Weller, Wolfgang Wick, Richard Bourgon, Josep Garcia
Journal: Neuro-Oncology (2020)

We aimed to develop a gene expression-based prognostic signature for isocitrate dehydrogenase (IDH) wild-type glioblastoma using clinical trial datasets representative of glioblastoma clinical trial populations.
Disparities in Influenza Vaccination—Opportunity to Extend Cardiovascular Prevention to Millions of Hearts
Authors: Laurence S. Sperling, Michelle A. Albert, Ram Koppaka
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
Bacterial and fungal superinfections in critically ill patients with COVID-19
Authors: Matteo Bassetti, Marin H. Kollef, Jean-Francois Timsit
Journal: Intensive Care Medicine (2020)

Are critically ill patients with coronavirus disease 2019 (COVID-19) at high risk of bacterial and fungal superinfections developing on the top of the viral infection in the lung or in other body sites?And from which organisms?Answering these apparently simple questions could be far more difficult than expected, for at least three important reasons.The first one is that the timing of development of superinfection (early or late) with respect to the intensive care unit (ICU) admission may have relevant clinical implications.Indeed, borrowing from experiences in other ICU populations it cannot be excluded a priori that early and late superinfections may be profoundly different in terms of risk [1, 2].However, early and late superinfections have been frequently lumped together in the currently available literature on COVID-19 patients, making it difficult to firmly grasp their separate risks [3, 4].The second reason is that the high case fatality of the viral disease per se may be an important competing risk for the development of late superinfection, which may lead to an unintended underestimation of the risk of superinfection at the bedside of alive patients.The third reason specifically involves invasive aspergillosis, for which the current absence of a standardized definition for non-proven disease in non-neutropenic critically ill patients may preclude a reliable risk assessment also in COVID-19 patients [5].In the next few paragraphs, we briefly discuss each of these three intertwined, important issues.
Should countries aim for elimination in the covid-19 pandemic?
Authors: Andrew Lee, Simon Thornley, Arthur J Morris, Gerhard Sundborn
Journal: BMJ (2020)

Elimination is possible and is the only way to prevent the biggest loss of life and economic harm in the long run, says <b>Andrew Lee</b>. But <b>Simon Thornley</b>, <b>Arthur J Morris</b>, and <b>Gerhard Sundborn</b> argue that the cost to quality of life years is too big a risk when "possible" is not the same as "achievable"
Restoration of RNA helicase DDX5 suppresses hepatitis B virus (HBV) biosynthesis and Wnt signaling in HBV-related hepatocellular carcinoma
Authors: Saravana Kumar Kailasam Mani, Bingyu Yan, Zhibin Cui, Jiazeng Sun, Sagar Utturkar, Adrien Foca, Nadim Fares, David Durantel, Nadia Lanman, Philippe Merle, Majid Kazemian, Ourania Andrisani
Journal: Theranostics (2020)

Rationale: RNA helicase DDX5 is downregulated during hepatitis B virus (HBV) replication, and poor prognosis HBV-related hepatocellular carcinoma (HCC). The aim of this study is to determine the mechanism and significance of DDX5 downregulation for HBV-driven HCC, and identify biologics to prevent DDX5 downregulation. Methods: Molecular approaches including immunoblotting, qRT-PCR, luciferase transfections, hepatosphere assays, Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq), and RNA-seq were used with cellular models of HBV replication, HBV infection, and HBV-related liver tumors, as well as bioinformatic analyses of liver cancer cells from two independent cohorts. Results: We demonstrate that HBV infection induces expression of the proto-oncogenic miR17~92 and miR106b~25 clusters which target the downregulation of DDX5. Increased expression of these miRNAs is also detected in HBV-driven HCCs exhibiting reduced DDX5 mRNA. Stable DDX5 knockdown (DDX5KD) in HBV replicating hepatocytes increased viral replication, and resulted in hepatosphere formation, drug resistance, Wnt activation, and pluripotency gene expression. ATAC-seq of DDX5KD compared to DDX5 wild-type (WT) cells identified accessible chromatin regions enriched in regulation of Wnt signaling genes. RNA-seq analysis comparing WT versus DDX5KD cells identified enhanced expression of multiple genes involved in Wnt pathway. Additionally, expression of Disheveled, DVL1, a key regulator of Wnt pathway activation, was significantly higher in liver cancer cells with low DDX5 expression, from two independent cohorts. Importantly, inhibitors (antagomirs) to miR17~92 and miR106b~25 restored DDX5 levels, reduced DVL1 expression, and suppressed both Wnt activation and viral replication. Conclusion : DDX5 is a negative regulator of Wnt signaling and hepatocyte reprogramming in HCCs. Restoration of DDX5 levels by miR17~92 / miR106b~25 antagomirs in HBV-infected patients can be explored as both antitumor and antiviral strategy.
Peroxiredoxin 6 mediates protective function of astrocytes in Aβ proteostasis
Authors: Joanna E. Pankiewicz, Jenny R. Diaz, Mitchell Martá-Ariza, Anita M. Lizińczyk, Leor A. Franco, Martin J. Sadowski
Journal: Molecular Neurodegeneration (2020)

Abstract Background Disruption of β-amyloid (Aβ) homeostasis is the initial culprit in Alzheimer’s disease (AD) pathogenesis. Astrocytes respond to emerging Aβ plaques by altering their phenotype and function, yet molecular mechanisms governing astrocytic response and their precise role in countering Aβ deposition remain ill-defined. Peroxiredoxin (PRDX) 6 is an enzymatic protein with independent glutathione peroxidase (Gpx) and phospholipase A2 (PLA 2 ) activities involved in repair of oxidatively damaged cell membrane lipids and cellular signaling. In the CNS, PRDX6 is uniquely expressed by astrocytes and its exact function remains unexplored. Methods APPswe/PS1 dE9 AD transgenic mice were once crossed to mice overexpressing wild-type Prdx6 allele or to Prdx6 knock out mice. Aβ pathology and associated neuritic degeneration were assessed in mice aged 10 months. Laser scanning confocal microscopy was used to characterize Aβ plaque morphology and activation of plaque-associated astrocytes and microglia. Effect of Prdx6 gene dose on plaque seeding was assessed in mice aged six months. Results We show that hemizygous knock in of the overexpressing Prdx6 transgene in APP swe /PS1 dE9 AD transgenic mice promotes selective enticement of astrocytes to Aβ plaques and penetration of plaques by astrocytic processes along with increased number and phagocytic activation of periplaque microglia. This effects suppression of nascent plaque seeding and remodeling of mature plaques consequently curtailing brain Aβ load and Aβ-associated neuritic degeneration. Conversely, Prdx6 haplodeficiency attenuates astro- and microglia activation around Aβ plaques promoting Aβ deposition and neuritic degeneration. Conclusions We identify here PRDX6 as an important factor regulating response of astrocytes toward Aβ plaques. Demonstration that phagocytic activation of periplaque microglia vary directly with astrocytic PRDX6 expression level implies previously unappreciated astrocyte-guided microglia effect in Aβ proteostasis. Our showing that upregulation of PRDX6 attenuates Aβ pathology may be of therapeutic relevance for AD.
Exploring Spatial-Temporal Changes in <sup>18</sup>F-Sodium Fluoride PET/CT and Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide
Authors: Christos E. Kyriakopoulos, Elisabeth I. Heath, Anna Ferrari, Jamie M. Sperger, Anupama Singh, Scott B. Perlman, Alison R. Roth, Timothy G. Perk, Katharina Modelska, Anthony Porcari, William Duggan, Joshua M. Lang, Robert Jeraj, Glenn Liu
Journal: Journal of Clinical Oncology (2020)

Intrapatient treatment response heterogeneity is under-recognized. Quantitative total bone imaging (QTBI) using 18F-NaF positron emission tomography/computed tomography (PET/CT) scans is a tool that allows characterization of interlesional treatment response heterogeneity in bone. Understanding spatial-temporal response is important to identify individuals who may benefit from treatment beyond progression.Men with progressive metastatic castration-resistant prostate cancer (mCRPC) with at least two lesions on bone scintigraphy were enrolled and treated with enzalutamide 160 mg daily (ClinicalTrials.gov identifier: NCT02384382). 18F-NaF PET/CT scans were obtained at baseline (PET1), week 13 (PET2), and at the time of prostate-specific antigen (PSA) progression, standard radiographic or clinical progression, or at 2 years without progression (PET3). QTBI was used to determine lesion-level response. The primary end point was the proportion of men with at least one responding bone lesion on PET3 using QTBI.Twenty-three men were enrolled. Duration on treatment ranged from 1.4 to 34.1 months. In general, global standardized uptake value (SUV) metrics decreased while on enzalutamide (PET2) and increased at the time of progression (PET3). The most robust predictor of PSA progression was change in SUVhetero (PET1 to PET3; hazard ratio, 3.88; 95% CI, 1.24 to 12.1). Although overall functional disease burden improved during enzalutamide treatment, an increase in total burden (SUVtotal) was seen at the time of progression, as measured by 18F-NaF PET/CT. All (22/22) evaluable men had at least one responding bone lesion at PET3 using QTBI.We found that the proportion of progressing lesions was low, indicating that a substantial number of lesions appear to continue to benefit from enzalutamide beyond progression. Selective targeting of nonresponding lesions may be a reasonable approach to extend benefit.
Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer
Authors: Bernhard Mlecnik, Carlo Bifulco, Gabriela Bindea, Florence Marliot, Alessandro Lugli, J. Jack Lee, Inti Zlobec, Tilman T. Rau, Martin D. Berger, Iris D. Nagtegaal, Elisa Vink-Börger, Arndt Hartmann, Carol Geppert, Julie Kolwelter, Susanne Merkel, Robert Grützmann, Marc Van den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Léonard, Christophe Remue, Julia Y. Wang, Prashant Bavi, Michael H. A. Roehrl, Pamela S. Ohashi, Linh T. Nguyen, SeongJun Han, Heather L. MacGregor, Sara Hafezi-Bakhtiari, Bradly G. Wouters, Giuseppe V. Masucci, Emilia K. Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Tessa Fredriksen, Bénédicte Buttard, Lucie Lafontaine, Daniela Bruni, Anastasia Lanzi, Carine El Sissy, Nacilla Haicheur, Amos Kirilovsky, Anne Berger, Christine Lagorce, Christopher Paustian, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn van de Water, Shannon van Lent–van Vliet, Nikki Knijn, Ana-Maria Muşină, Dragos-Viorel Scripcariu, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Toshihiko Torigoe, Noriyuki Sato, Tomohisa Furuhata, Ichiro Takemasa, Kyogo Itoh, Prabhu S. Patel, Hemangini H. Vora, Birva Shah, Jayendrakumar B. Patel, Kruti N. Rajvik, Shashank J. Pandya, Shilin N. Shukla, Yili Wang, Guanjun Zhang, Yutaka Kawakami, Francesco M. Marincola, Paolo A. Ascierto, Bernard A. Fox, Franck Pagès, Jérôme Galon
Journal: Journal of Clinical Oncology (2020)

The purpose of this study was to evaluate the prognostic value of Immunoscore in patients with stage III colon cancer (CC) and to analyze its association with the effect of chemotherapy on time to recurrence (TTR).
Astrocytes Control Sensory Acuity via Tonic Inhibition in the Thalamus
Authors: Hankyul Kwak, Wuhyun Koh, Sangwoo Kim, Kiyeong Song, Jeong-Im Shin, Jung Moo Lee, Elliot H. Lee, Jin Young Bae, Go Eun Ha, Ju-Eun Oh, Yongmin Mason Park, Sunpil Kim, Jiesi Feng, Seung Eun Lee, Ji Won Choi, Ki Hun Kim, Yoo Sung Kim, Junsung Woo, Dongsu Lee, Taehwang Son, Soon Woo Kwon, Ki Duk Park, Bo-Eun Yoon, Jaeick Lee, Yulong Li, Hyunbeom Lee, Yong Chul Bae, C. Justin Lee, Eunji Cheong
Journal: Neuron (2020)
Oral delivery of anti-TNF antibody shielded by natural polyphenol-mediated supramolecular assembly for inflammatory bowel disease therapy
Authors: Xinyu Wang, Junjie Yan, Lizhen Wang, Donghui Pan, Yuping Xu, Fang Wang, Jie Sheng, Xinxin Li, Min Yang
Journal: Theranostics (2020)

Rationale: Anti-tumor necrosis factor (TNF) therapy is a very effective way to treat inflammatory bowel disease. However, systemic exposure to anti-TNF-α antibodies through current clinical systemic administration can cause serious adverse effects in many patients. Here, we report a facile prepared self-assembled supramolecular nanoparticle based on natural polyphenol tannic acid and poly(ethylene glycol) containing polymer for oral antibody delivery. Method: This supramolecular nanoparticle was fabricated within minutes in aqueous solution and easily scaled up to gram level due to their pH-dependent reversible assembly. DSS-induced colitis model was prepared to evaluate the ability of inflammatory colon targeting ability and therapeutic efficacy of this antibody-loaded nanoparticles. Results: This polyphenol-based nanoparticle can be aqueous assembly without organic solvent and thus scaled up easily. The oral administration of antibody loaded nanoparticle achieved high accumulation in the inflamed colon and low systemic exposure. The novel formulation of anti-TNF-α antibodies administrated orally achieved high efficacy in the treatment of colitis mice compared with free antibodies administered orally. The average weight, colon length, and inflammatory factors in colon and serum of colitis mice after the treatment of novel formulation of anti-TNF-α antibodies even reached the similar level to healthy controls. Conclusion: This polyphenol-based supramolecular nanoparticle is a promising platform for oral delivery of antibodies for the treatment of inflammatory bowel diseases, which may have promising clinical translation prospects.
Authors should have used marginal analysis
Authors: D. J Torgerson
Journal: BMJ (1996)

Censuses and Surveys' omnibus survey shows that only 2 1% of families with children contain children from both a previous and the current partner.3This proportion is low because, although many people change partners, they tend to do so after they have had most of their children.An unknown proportion of families with lone mothers contain two or more children of different fathers; if this proportion were half it would represent an extra 4% of all families with children.This would make the cost of the two screening methods similar.The main reason, however, for preferring couple screening is not economic but medical.4In sequential screening 97% of women who are positive on screening will have a partner who is negative, some of whom will carry a mutation for cystic fibrosis that cannot be detected.These women may resent the anxiety generated by being identified as a carrier, with the resultant increased risk of an affected pregnancy but no diagnostic test available to resolve the uncertainty.This problem is avoided in couple screening, as carriers with non-carrier partners are regarded as being negative on screening.