tbuckley/cabot-search huggingface dataset:
Drug-Induced Hepatotoxicity
Authors: William M. Lee
Journal: New England Journal of Medicine (2003)

Drug-induced hepatic injury accounts for more than 50 percent of cases of acute liver failure in the United States. More than 75 percent of idiosyncratic drug reactions result in liver transplantation or death. This review discusses the pathogenesis of drug-induced liver injury, common adverse drug reactions involving the liver, and the drug-approval process. Monitoring for and recognition of drug-induced hepatotoxicity may prevent some cases of acute hepatic failure.
An International Real-World Analysis of the Efficacy and Safety of Lorlatinib Through Early or Expanded Access Programs in Patients With Tyrosine Kinase Inhibitor–Refractory ALK-Positive or ROS1-Positive NSCLC
Authors: Viola W. Zhu, Yen-Ting Lin, Dong-Wan Kim, Herbert H. Loong, Misako Nagasaka, Hao To, Yvonne Li-En Ang, Chan-Young Ock, Nishan Tchekmedyian, Sai-Hong Ignatius Ou, Nicholas L. Syn, Thanyanan Reungwetwattana, Chia-Chi Lin, Ross A. Soo
Journal: Journal of Thoracic Oncology (2020)

IntroductionLorlatinib, a next-generation central nervous system–penetrant ALK/ROS1 tyrosine kinase inhibitor (TKI), is approved to treat TKI-refractory ALK-positive (ALK+) NSCLC based on results from a phase 2 study.MethodsA real-world analysis was performed on ALK+ or ROS1-positive (ROS1+) patients with NSCLC enrolled in lorlatinib early or expanded access programs in Hong Kong, Singapore, South Korea, Taiwan, Thailand, and the United States.ResultsA total of 95 patients with NSCLC (76 ALK+ and 19 ROS1+) were analyzed. Among ALK+ patients treated with less than two previous TKIs, two or more previous TKIs, and three or more previous TKIs, the objective response rates (ORR) and median progression-free survival (mPFS) were 42% (95% confidence interval [CI]: 26–59; n = 38) and not reached (NR) (95% CI: 4.5–NR; n = 45), 35% (95% CI: 22–49; n = 55) and 11.2 months (95% CI: 4.5–NR; n = 66), and 18% (95% CI: 4–43; n = 17) and 6.5 months (95% CI: 3.5–11.6; n = 21), respectively. The ORRs and mPFSs were 13% (95% CI: 0–53; n = 8) and 9.2 months (95% CI: 3.3–NR; n = 9) for patients treated with one second-generation ALK TKI as the only ALK TKI received. For ROS1+ patients, ORRs and mPFSs were 41% (95% CI: 18–67; n = 17) and 11.9 months (95% CI: 6.4–NR; n = 19). The intracranial ORRs were 35% (95% CI: 22–49) and 55% (95% CI: 23–83) for 52 ALK+ and 11 ROS1+ patients. mPFS was 9.3 months (95% CI: 1.0–NR; n = 13) for patients with leptomeningeal carcinomatosis. No new safety signals were noted.ConclusionLorlatinib exhibited meaningful activity in TKI-refractory ALK+ or ROS1+ patients with NSCLC enrolled in early or expanded access programs.
Digitate Papulosquamous Eruption Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Adrien Sanchez, Pierre Sohier, Sarah Benghanem, Anne-Sophie L’Honneur, Flore Rozenberg, Nicolas Dupin, Bethsabée Garel
Journal: JAMA Dermatology (2020)

This case report describes an elderly patient who developed a squamous and erythematous periumbilical patch followed by digitate scaly thin plaques and papular lesions in conjunction with severe acute respiratory syndrome coronavirus 2 infection.
An Association between the Risk of Cancer and Mutations in the HRAS1 Minisatellite Locus
Authors: Theodore G. Krontiris, B. Devlin, Daniel D. Karp, Nicholas J. Robert, Neil Risch
Journal: New England Journal of Medicine (1993)

The role of mutations in proto-oncogenes and their regulatory sequences in the pathogenesis of cancer is under close scrutiny. Minisatellites are unstable repetitive sequences of DNA that are present throughout the human genome. The highly polymorphic HRAS1 minisatellite locus just downstream from the proto-oncogene H-ras-1 consists of four common progenitor alleles and several dozen rare alleles, which apparently derive from mutations of the progenitors. We previously observed an association of the rare mutant alleles with many forms of cancer, and we undertook the present study to pursue this observation further.
The Speckled Protein (SP) Family: Immunity’s Chromatin Readers
Authors: Isabella Fraschilla, Kate L. Jeffrey
Journal: Trends in Immunology (2020)

Chromatin 'readers' are central interpreters of the epigenome that facilitate cell-specific transcriptional programs and are therapeutic targets in cancer and inflammation. The Speckled Protein (SP) family of chromatin 'readers' in humans consists of SP100, SP110, SP140, and SP140L. SPs possess functional domains (SAND, PHD, bromodomain) that dock to DNA or post-translationally modified histones and a caspase activation and recruitment domain (CARD) to promote multimerization. Mutations within immune expressed SPs associate with numerous immunological diseases including Crohn's disease, multiple sclerosis, chronic lymphocytic leukemia, veno-occlusive disease with immunodeficiency, as well as Mycobacterium tuberculosis infection, underscoring their importance in immune regulation. In this review, we posit that SPs are central chromatin regulators of gene silencing that establish immune cell identity and function.
Autologous haematopoietic stem-cell transplantation versus bortezomib–melphalan–prednisone, with or without bortezomib–lenalidomide–dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study
Authors: Michele Cavo, Francesca Gay, Meral Beksac, Lucia Pantani, Maria Teresa Petrucci, Meletios A Dimopoulos, Luca Dozza, Bronno van der Holt, Sonja Zweegman, Stefania Oliva, Vincent H J van der Velden, Elena Zamagni, Giuseppe A Palumbo, Francesca Patriarca, Vittorio Montefusco, Monica Galli, Vladimir Maisnar, Barbara Gamberi, Markus Hansson, Angelo Belotti, Ludek Pour, Paula Ypma, Mariella Grasso, Alexsandra Croockewit, Stelvio Ballanti, Massimo Offidani, Iolanda D Vincelli, Renato Zambello, Anna Marina Liberati, Niels Frost Andersen, Annemiek Broijl, Rossella Troia, Anna Pascarella, Giulia Benevolo, Mark-David Levin, Gerard Bos, Heinz Ludwig, Sara Aquino, Anna Maria Morelli, Ka Lung Wu, Rinske Boersma, Roman Hajek, Marc Durian, Peter A von dem Borne, Tommaso Caravita di Toritto, Thilo Zander, Christoph Driessen, Giorgina Specchia, Anders Waage, Peter Gimsing, Ulf-Henrik Mellqvist, Marinus van Marwijk Kooy, Monique Minnema, Caroline Mandigers, Anna Maria Cafro, Angelo Palmas, Susanna Carvalho, Andrew Spencer, Mario Boccadoro, Pieter Sonneveld
Journal: The Lancet Haematology (2020)
How to select IgG subclasses in developing anti-tumor therapeutic antibodies
Authors: Jifeng Yu, Yongping Song, Wenzhi Tian
Journal: Journal of Hematology & Oncology (2020)

Abstract The intact antibody of human immunoglobulin (IgG) is composed of the fragment for antigen binding (Fab) and the crystallizable fragment (Fc) for binding of Fcγ receptors. Among the four subclasses of human IgG (IgG1, IgG2, IgG3, IgG4), which differ in their constant regions, particularly in their hinges and CH2 domains, IgG1 has the highest FcγR-binding affinity, followed by IgG3, IgG2, and IgG4. As a result, different subclasses have different effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Fcγ receptors include six subtypes (FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, FcγRIIIB) which differ in cellular distribution, binding affinity to Fc, and the resulting biological activity. Therefore, when developing anti-tumor therapeutic antibodies, including single-targeted antibodies, bi-specific antibodies (BsAbs), and antibody-drug conjugates (ADCs), many factors, such as target biology, cellular distribution of the targets, the environments of particular tumor types, as well as the proposed mechanism of action (MOA), must be taken into consideration. This review outlines fundamental strategies that are required to select IgG subclasses in developing anti-tumor therapeutic antibodies.
Connect MDS and AML: The myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) disease registry.
Authors: David P. Steensma, Mehrdad Abedi, Eyal C. Attar, Rafael Bejar, Christopher R. Cogle, Guillermo Garcia-Manero, David L. Grinblatt, Xiaomei Ma, Jaroslaw P. Maciejewski, Daniel Aaron Pollyea, Gail J. Roboz, Michael Savona, Bart L. Scott, Mikkael A. Sekeres, Michael A. Thompson, Oleg Zernovak, Mary M. Sugrue, Arlene S. Swern, Melissa Nifenecker, Harry Paul Erba
Journal: Journal of Clinical Oncology (2014)

TPS7126 Background: Diagnostic approaches, treatment (tx) patterns, and clinical outcomes for patients (pts) with MDS or AML outside of clinical trials are poorly characterized. The Connect MDS and AML Registry (Clinicaltrials.gov Identifier NCT01688011) is a prospective, longitudinal, multicenter observational registry for pts newly diagnosed with MDS or AML. It is designed to capture diagnostic evaluation, risk assessment, and tx patterns; objective clinical and pt-reported outcomes (PROs); and biospecimens from pts cared for in community or academic centers. Methods: Approximately 1,500 pts from ≈ 150 clinical sites across the United States will be enrolled into 4 cohorts: IPSS low/Int-1–risk MDS (n = 700, including ≈ 250 del(5q) MDS), Int-2/high-risk MDS (n = 200), unknown-risk MDS due to unsuccessful bone marrow cytogenetics (n = 100), and AML (n = 500). Pts must have confirmed newly diagnosed (≤ 60 days prior to enrollment) MDS or primary or secondary AML, excluding acute promyelocytic leukemia, based on WHO 2008 diagnostic criteria. AML pts must be ≥ 55 years of age. First pt was enrolled in December 2013. Pts will be followed for up to 8 years, until withdrawal from the study, death, or study end. There will be 1 initial remote monitoring visit. Appropriate methods for observational data will be utilized. Primary objectives are to describe current and evolving patterns of diagnosis/prognosis, evaluation, tx, clinical monitoring, and outcomes; compare actual clinical practice with existing management guidelines; describe tx sequencing and associated short- and long-term outcomes, including response, safety, disease progression, and survival; and summarize PROs and health economic outcomes and their association with pt characteristics, tx, and clinical outcomes. Additionally, biospecimens will be collected for correlative studies, including assessment of somatic mutations. Registry results may provide new insights into how tx regimens and tx sequencing data combined with baseline prognostic factors relate to clinical outcomes of pts with MDS or AML. Furthermore, PROs and correlative molecular data will help elucidate the association of tx patterns with relevant effectiveness outcomes.
Statement on methods in sport injury research from the 1st METHODS MATTER Meeting, Copenhagen, 2019
Authors: Rasmus Oestergaard Nielsen, Ian Shrier, Marti Casals, Albertro Nettel-Aguirre, Merete Møller, Caroline Bolling, Natália Franco Netto Bittencourt, Benjamin Clarsen, Niels Wedderkopp, Torbjørn Soligard, Toomas Timpka, Carolyn Emery, Roald Bahr, Jenny Jacobsson, Rod Whiteley, Orjan Dahlstrom, Nicol van Dyk, Babette M Pluim, Emmanuel Stamatakis, Luz Palacios-Derflingher, Morten Wang Fagerland, Karim M Khan, Clare L Ardern, Evert Verhagen
Journal: British Journal of Sports Medicine (2020)

High quality sports injury research can facilitate sports injury prevention and treatment. There is scope to improve how our field applies best practice methods—methods matter (greatly!). The 1st METHODS MATTER Meeting, held in January 2019 in Copenhagen, Denmark, was the forum for an international group of researchers with expertise in research methods to discuss sports injury methods. We discussed important epidemiological and statistical topics within the field of sports injury research. With this opinion document, we provide the main take-home messages that emerged from the meeting.
Tumarkin Drop Attack Recorded by Video Surveillance
Authors: Zichen Chen, Yuzhong Zhang, Qing Zhang
Journal: JAMA Neurology (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 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
Macrophages Expressing GALC Improve Peripheral Krabbe Disease by a Mechanism Independent of Cross-Correction
Authors: Nadav I. Weinstock, Daesung Shin, Narayan Dhimal, Xinying Hong, Eric E. Irons, Nicholas J. Silvestri, Chelsey B. Reed, Duc Nguyen, Oliver Sampson, Yung-Chih Cheng, Joseph T.Y. Lau, Ernesto R. Bongarzone, Julia Kofler, Maria L. Escolar, Michael H. Gelb, Lawrence Wrabetz, M. Laura Feltri
Journal: Neuron (2020)
Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset
Authors: Hao-Yuan Cheng, Shu-Wan Jian, Ding-Ping Liu, Ta-Chou Ng, Wan-Ting Huang, Hsien-Ho Lin
Journal: JAMA Internal Medicine (2020)

<h3>Importance</h3> The dynamics of coronavirus disease 2019 (COVID-19) transmissibility are yet to be fully understood. Better understanding of the transmission dynamics is important for the development and evaluation of effective control policies. <h3>Objective</h3> To delineate the transmission dynamics of COVID-19 and evaluate the transmission risk at different exposure window periods before and after symptom onset. <h3>Design, Setting, and Participants</h3> This prospective case-ascertained study in Taiwan included laboratory-confirmed cases of COVID-19 and their contacts. The study period was from January 15 to March 18, 2020. All close contacts were quarantined at home for 14 days after their last exposure to the index case. During the quarantine period, any relevant symptoms (fever, cough, or other respiratory symptoms) of contacts triggered a COVID-19 test. The final follow-up date was April 2, 2020. <h3>Main Outcomes and Measures</h3> Secondary clinical attack rate (considering symptomatic cases only) for different exposure time windows of the index cases and for different exposure settings (such as household, family, and health care). <h3>Results</h3> We enrolled 100 confirmed patients, with a median age of 44 years (range, 11-88 years), including 44 men and 56 women. Among their 2761 close contacts, there were 22 paired index-secondary cases. The overall secondary clinical attack rate was 0.7% (95% CI, 0.4%-1.0%). The attack rate was higher among the 1818 contacts whose exposure to index cases started within 5 days of symptom onset (1.0% [95% CI, 0.6%-1.6%]) compared with those who were exposed later (0 cases from 852 contacts; 95% CI, 0%-0.4%). The 299 contacts with exclusive presymptomatic exposures were also at risk (attack rate, 0.7% [95% CI, 0.2%-2.4%]). The attack rate was higher among household (4.6% [95% CI, 2.3%-9.3%]) and nonhousehold (5.3% [95% CI, 2.1%-12.8%]) family contacts than that in health care or other settings. The attack rates were higher among those aged 40 to 59 years (1.1% [95% CI, 0.6%-2.1%]) and those aged 60 years and older (0.9% [95% CI, 0.3%-2.6%]). <h3>Conclusions and Relevance</h3> In this study, high transmissibility of COVID-19 before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized measures may be required, such as social distancing.
Gut microbiome communication with bone marrow regulates susceptibility to amebiasis
Authors: Stacey L. Burgess, Jhansi L. Leslie, Jashim Uddin, David N. Oakland, Carol Gilchrist, G. Brett Moreau, Koji Watanabe, Mahmoud Saleh, Morgan Simpson, Brandon A. Thompson, David T. Auble, Stephen D. Turner, Natasa Giallourou, Jonathan Swann, Zhen Pu, Jennie Z. Ma, Rashidul Haque, William A. Petri
Journal: Journal of Clinical Investigation (2020)

The microbiome provides resistance to infection. However, the underlying mechanisms are poorly understood. We demonstrate that colonization with the intestinal bacterium Clostridium scindens protects from Entamoeba histolytica colitis via innate immunity. Introduction of C. scindens into the gut microbiota epigenetically altered and expanded bone marrow granulocyte-monocyte progenitors (GMPs) and resulted in increased intestinal neutrophils with subsequent challenge with E. histolytica. Introduction of C. scindens alone was sufficient to expand GMPs in gnotobiotic mice. Adoptive transfer of bone marrow from C. scindens-colonized mice into naive mice protected against amebic colitis and increased intestinal neutrophils. Children without E. histolytica diarrhea also had a higher abundance of Lachnoclostridia. Lachnoclostridia C. scindens can metabolize the bile salt cholate, so we measured deoxycholate and discovered that it was increased in the sera of C. scindens-colonized specific pathogen-free and gnotobiotic mice, as well as in children protected from amebiasis. Administration of deoxycholate alone increased GMPs and provided protection from amebiasis. We elucidated a mechanism by which C. scindens and the microbially metabolized bile salt deoxycholic acid alter hematopoietic precursors and provide innate protection from later infection with E. histolytica.
Nosocomial outbreak of COVID-19 pneumonia in Wuhan, China
Authors: Xiaorong Wang, Qiong Zhou, Yukun He, Lingbo Liu, Xinqian Ma, Xiaoshan Wei, Nanchuan Jiang, Limei Liang, Yali Zheng, Ling Ma, Yu Xu, Dong Yang, Jianchu Zhang, Bohan Yang, Ning Jiang, Tao Deng, Bingbing Zhai, Yang Gao, Wenxuan Liu, Xinghua Bai, Tao Pan, Guoqing Wang, Yujun Chang, Zhi Zhang, Huanzhong Shi, Wan-Li Ma, Zhancheng Gao
Journal: European Respiratory Journal (2020)

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infected over 3300 healthcare workers in early 2020 in China. Little information is known about nosocomial infections of healthcare workers in the initial period. We analysed data from healthcare workers with nosocomial infections in Wuhan Union Hospital (Wuhan, China) and their family members.We collected and analysed data on exposure history, illness timelines and epidemiological characteristics from 25 healthcare workers with laboratory-confirmed coronavirus disease 2019 (COVID-19) and two healthcare workers in whom COVID-19 was highly suspected, as well as 10 of their family members with COVID-19, between 5 January and 12 February 2020. The demographics and clinical features of the 35 laboratory-confirmed cases were investigated and viral RNA of 12 cases was sequenced and analysed.Nine clusters were found among the patients. All patients showed mild to moderate clinical manifestation and recovered without deterioration. The mean period of incubation was 4.5 days, the mean±sd clinical onset serial interval (COSI) was 5.2±3.2 days, and the median virus shedding time was 18.5 days. Complete genomic sequences of 12 different coronavirus strains demonstrated that the viral structure, with small irrelevant mutations, was stable in the transmission chains and showed remarkable traits of infectious traceability.SARS-CoV-2 can be rapidly transmitted from person to person, regardless of whether they have symptoms, in both hospital settings and social activities, based on the short period of incubation and COSI. The public health service should take practical measures to curb the spread, including isolation of cases, tracing close contacts, and containment of severe epidemic areas. Besides this, healthcare workers should be alert during the epidemic and self-quarantine if self-suspected of infection.
Hepatitis B and C coinfections and persistent hepatitis B infections: Clinical outcome and liver pathology after transplantation
Authors: E HUANG
Journal: Hepatology (1996)

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are common complications after orthotopic liver transplantation (OLT), but the liver pathology and clinical outcomes of HBV infection with HCV coinfection have not been thoroughly examined. In this study, we used the polymerase chain reaction (PCR) to detect HBV and HCV in pre- and post-OLT sera of 38 patients and correlated the findings with clinical outcome and liver pathology. Of 13 patients who were HBV and HCV negative before OLT, 9 acquired HBV infection, and 4 developed acquired HBV and HCV coinfections after OLT. Persistent HBV infections were present in 10 patients. Three patients with pre-OLT HBV infections developed persistent HBV and acquired HCV coinfections after OLT; 5 with pre-OLT HCV infections developed acquired HBV and persistent HCV coinfections after OLT, and 7 had persistent HBV and HCV coinfections before and after OLT. Portal/periportal inflammation was the same in all groups; however, lobular inflammation and fibrosis were more severe in patients with persistent HBV infections and in those with acquired HBV and HCV coinfections. Two major histopathological patterns were present in patients with HBV and HCV coinfections, one with predominant features of HCV infection, and the other with those of HBV infection. Patients with post-OLT HBV and HCV coinfections had survival rates similar to those with acquired HBV infection, whereas patients with persistent HBV infections experienced more allograft loss caused by chronic hepatitis or fibrosing cytolytic hepatitis, and had a more dire clinical outcome than the others. Although the limited numbers reported in this study prevent a definitive conclusion, our data suggest that in patients with HBV and HCV coinfections, the presence of HCV may improve the clinical outcome as compared with the expected outcome of persistent HBV infection alone.