tbuckley/cabot-search huggingface dataset:
Effect Size and Blinding in Lumateperone Trial
Authors: Brittany M. Gouse, Alexander L. Chang, Eric G. Smith
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Abstract IA20: Gut microbiota dysbiosis and dietary fermentable fibers in a pickle: A brew for liver cancer
Authors: Matam Vijay-Kumar
Journal: Cancer Research (2020)

Abstract Dietary soluble fibers are fermented by gut bacteria into short-chain fatty acids (SCFA), which are considered broadly health promoting. Accordingly, consumption of such fibers ameliorates metabolic syndrome in a subset (40%) of Toll-like receptor 5-deficient (TLR5KO) mice. However, incorporating fermentable fiber inulin, but not nonfermentable fiber cellulose, into a compositionally defined purified diet induced hyperbilirubinemia and cholemia as primary clinical symptoms and hallmarks of cholestasis. These cholestatic mice eventually developed robust, multinodular hepatocellular carcinoma (HCC; a type of liver cancer) within 6 months. Inulin-induced HCC progressed via early onset of cholestasis, hepatocyte death, followed by liver inflammation primarily driven by neutrophils. Such neutrophilic inflammation is characterized by elevated levels of neutrophil elastase and myeloperoxidase, and hepatic reactive oxygen species, malondialdehyde and 8-hydroxy-2’-deoxyguanosine, a marker of DNA damage. Pathogenesis of such HCC was microbiota dependent and observed in multiple strains of dysbiotic mice, but not in germ-free or antibiotics-treated TLR5KO mice. Furthermore, inulin-enriched diet induced both dysbiosis and HCC in wild-type (WT) mice co-housed or cross-fostered with TLR5KO mice. Pharmacologic inhibition of fermentation or depletion of fermenting bacteria markedly reduced intestinal SCFA and prevented HCC. Intervening with cholestyramine to prevent enterohepatic recirculation of bile acids also conferred protection against such HCC. Thus, notwithstanding the health benefits of inulin, enrichment of foods with fermentable fiber should be approached with great caution as it may increase risk of HCC and warrants that refined fibers need to be redefined. Citation Format: Matam Vijay-Kumar. Gut microbiota dysbiosis and dietary fermentable fibers in a pickle: A brew for liver cancer [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA20.
Abstract IA24: Engineered <i>Salmonella</i> for drug delivery to solid tumors
Authors: Neil S. Forbes
Journal: Cancer Research (2020)

Abstract Engineered bacteria have the potential to overcome the limitations that cause cancer therapies to fail. We are engineering bacteria to deliver therapeutic payloads and quantifying the mechanisms that control bacterial therapy. We have shown that bacteria preferentially target tumors and actively penetrate tissue. Bacterial motility has a linear relationship with colonization density. Manipulating chemoreceptors in the membrane can direct bacteria to drug-resistant tumor regions, and inducing inflammation can promote colonization by modifying tumor vasculature. When engineered to express α-hemolysin from Staphylococcus aureus, bacteria kill 99% of culture cells in 5 minutes and reduce tumor volume in mice. Engineering Salmonella with quorum-sensing provides a density-dependent switch that induces protein expression only after bacteria have colonized tumor tissue. This technique prevents system toxicity after delivery of therapeutic molecules. We have also developed bacteria that selectively invade cancer cells and release molecules that modulate epigenetic targets, e.g., EZH2 and PP1. Salmonella were engineered with a genetic cassette that induces lysis specifically after invasion into mammalian cells. Lysis releases the bacterial content into the cytoplasm of cells. In culture, Salmonella lyse inside cancer cells and release GFP, which diffuses throughout the cellular cytoplasm. Releasing a peptide that interferes with the binding of the phosphatase, PP1, with its regulator, NIPP1, induces cell death after bacterial lysis. In three-dimensional tissue culture, administration of these bacteria induces cell death. These techniques establish Salmonella as a tunable platform for cancer therapy. By understanding the mechanisms of bacterial delivery, new strategies will be developed to treat hard-to-treat cancers. Citation Format: Neil S. Forbes. Engineered Salmonella for drug delivery to solid tumors [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA24.
Utility of routine screening for alpha-1 antitrypsin deficiency in patients with bronchiectasis
Authors: Luis Carreto, Meghan Morrison, Jackie Donovan, Simon Finch, Gan Liang Tan, Tom Fardon, Robert Wilson, Elisabeth Furrie, Michael Loebinger, James D Chalmers
Journal: Thorax (2020)

Alpha-1 antitrypsin deficiency (AATD) is a cause of bronchiectasis. Guidelines for bronchiectasis from the British Thoracic Society do not recommend to routinely test patients for AATD. In contrast, guidelines for AATD recommend routine screening. This contradiction, in part, results from the lack of data from large studies performing comprehensive screening. We screened 1600 patients with bronchiectasis at two centres in the UK from 2012 to 2016. In total, only eight individuals with AATD were identified representing 0.5% of the overall population. We conclude that routine screening for AATD in bronchiectasis in the UK has a low rate of detection. Further studies are required in different geographical regions, which may have a higher prevalence of AATD.
Effectiveness of darbepoetin alfa 300 mcg every 3 weeks in patients with chemotherapy-induced anemia
Authors: E. Hernandez, J. Dibenedetto, D. Kotasek, P. Ganly, P. Silberstein, D. Tomita, T. Lillie, R. V. Boccia
Journal: Journal of Clinical Oncology (2006)

18545 Background: Patients (pts) receiving chemotherapy (CTX) often experience anemia resulting in decreased quality of life. We performed a post hoc combined analysis of 2 clinical studies of darbepoetin alfa (DA) 300 mcg every 3 weeks (Q3W), allowing for comparison of larger treatment groups. Methods: Eligibility criteria of the 2 studies were similar: pts ≥ 18 yrs old with nonmyeloid malignancy, anemia (hemoglobin [Hb] &lt; 11 g/dL), and receiving CTX. Study 1 (20030232) was a phase 3, randomized, placebo-controlled, double-blind, study involving 16 wks of treatment with end of treatment phase (EOTP) visit at wk 19. Study 2 (20030206) was a single-arm, open-label, phase 4 study involving 13-wks of treatment with EOTP visit at wk 16. Efficacy endpoints included: percentage of pts achieving target Hb (≥ 11 g/dL without RBC transfusion [TFN] within 28 days), pts requiring TFNs between wk 1 and EOTP, pts requiring TFNs between wk 5 and EOTP, pts with a ≥ 3-point change in FACT-F score, and pts achieving ≥ 1-g/dL increase in Hb after 4 wks of therapy. Results: In both studies, 61% of pts were women and 79% were white. The mean (SD) age was 64.5 years (12.1) for Study 1 and 62.6 years (13.3) for Study 2. The most common tumor type was breast (26% in Study 1; 29% in Study 2). Mean (SD) baseline (BL) Hb values were 10.1 (0.9) and 10.1 (0.7) g/dL for Study 1 and Study 2 respectively, and mean (SD) baseline FACT-F scores were 27.3 (12.8) and 27.9 (12.3) respectively. See Table for endpoints. Combined analysis showed that increasing Hb by ≥ 1 g/dL after 4 wks of therapy was a poor predictor of clinical outcomes (avoidance of TFN, sensitivity = 56.2%; achievement of Hb target, sensitivity = 57.8%). Safety outcomes were similar and expected for this population. DA appeared to be well-tolerated. No pts exhibited neutralizing antibodies to DA. Conclusions: This combined analysis provides further evidence of the effectiveness of DA Q3W dosing in this pt population. This dosing interval may facilitate the administration of DA in synchronization with Q3W CTX regimens. [Table: see text] [Table: see text]
C3-Mediated Extravascular Hemolysis as Additional Mechanism of Disease in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients Treated by the Complent Inhibitor Eculizumab
Authors: Antonio M. Risitano, Ludovica Marando, Danilo Ranaldi, Elisa Seneca, Bianca Serio, Giacomo Gianfaldoni, Elisabetta Antonioli, Filippo Milano, Angela Amendola, Carla Boschetti, Wilma Barcellini, Eros Di Bona, Angelo Michele Carella, Filippo Barbano, Silvana Bonfigli, Silvana Capalbo, Francesco Fabbiano, Stefano Pulini, Antonio Marino, Francesco Pietrogrande, Franco Iuliano, Francesco Rodeghiero, Alberto Zanella, Annapaola Iori, Rosario Notaro, Lucio Luzzatto, Bruno Rotoli
Journal: Blood (2008)
Single Base Pair Mutation Detection by PNA Direct PCR Clamping: Application to Bcr-Abl T315I Mutation
Authors: Enrico Bracco, Roberto Pedrola, Marco Lo Iacono, Francesca Arruga, Valentina Rosso, Erika Deklic, Stefano Mussino, Sonia Carturan, Francesca Messa, Ilaria Defilippi, Cristina Panuzzo, Paolo Nicoli, Emanuela Messa, Antonia Rotolo, Alessandro Morotti, Alessandra Balbo, Margherita Valente, Roberto Sapio, Daniela Cilloni, Giuseppe Saglio
Journal: Blood (2008)
Abstract 13493: Brain Natriuretic Peptide is an Independent Prognostic Factor in Patient With Late-Stage Duchenne Muscular Dystrophy
Authors: Jung-Joon Cha, Young Hak Jung, Chul Shin, Ju Young Kim, Eui-Young Choi, Jong-Youn Kim, Pil-Ki Min, Young Won Yoon, Byoung-Kwon Lee, Bum-Kee Hong, Hyuck Moon Kwon, Won Ah Choi, Seong-Woong Kang, Se-Joong Rim
Journal: Circulation (2019)

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder which leads to progressive muscle degeneration including pulmonary and cardiac dysfunction. We have previously shown ...
Fully covered self-expandable metal stents for benign biliary strictures: an effective alternative
Authors: Djuna L. Cahen
Journal: Endoscopy (2020)

Endoscopic treatment for benign biliary strictures (BBSs) has been widely accepted. However, for refractory strictures, especially for hilar anastomotic strictures after living-donor liver transplants and hepaticojejunostomies, endoscopic treatment remains a challenge. The hilar location, with its small caliber ducts, can complicate the insertion of multiple plastic stents. The use of fully covered self-expandable metal stents (FCSEMSs) may be an attractive option in this setting, but this had not, to date, been properly investigated.
Cleaning and Disinfectant Chemical Exposures and Temporal Associations with COVID-19 — National Poison Data System, United States, January 1, 2020–March 31, 2020
Authors: Arthur Chang, Amy H. Schnall, Royal Law, Alvin C. Bronstein, Jeanna M. Marraffa, Henry A. Spiller, Hannah L. Hays, Alexandra R. Funk, Maria Mercurio-Zappala, Diane P. Calello, Alfred Aleguas, Douglas J. Borys, Tegan Boehmer, Erik Svendsen
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

the state of Washington reported the first U.S. laboratory-confirmed case of coronavirus disease 2019 (COVID-19) caused by infection with SARS-CoV-2 (1).As of April 19, a total of 720,630 COVID-19 cases and 37,202 associated deaths* had been reported to CDC from all 50 states, the District of Columbia, and four U.S. territories (2).CDC recommends, with precautions, the proper cleaning and disinfection of high-touch surfaces to help mitigate the transmission of SARS-CoV-2 (3).To assess whether there might be a possible association between COVID-19 cleaning recommendations from public health agencies and the media and the number of chemical exposures reported to the National Poison Data System (NPDS), CDC and the American Association of Poison Control Centers surveillance team compared the number of exposures reported for the period January-March 2020 with the number of reports during the same 3-month period in 2018 and 2019.Fifty-five poison centers in the United States provide free, 24-hour professional advice and medical management information regarding exposures to poisons, chemicals, drugs, and medications.Call data from poison centers are uploaded in near real-time to NPDS.During January-March 2020, poison centers received 45,550 exposure calls related to cleaners (28,158) and disinfectants (17,392), representing overall increases of 20.4% and 16.4% from January-March 2019 (37,822) and January-March 2018 (39,122), respectively.Although NPDS data do not provide information showing a definite link between exposures and COVID-19 cleaning efforts, there appears to be a clear temporal association with increased use of these products.The daily number of calls to poison centers increased sharply at the beginning of March 2020 for exposures to both cleaners and disinfectants (Figure).The increase in total calls was seen across all age groups; however, exposures among children aged ≤5 years consistently represented a large percentage of total calls in the 3-month study period for each year (range = 39.9%-47.3%)(Table ).Further analysis of the increase in calls from 2019 to 2020 (3,137 for cleaners, 4,591 for disinfectants), * Total cases include 1,282 probable cases, and total deaths include 4,226 probable associated deaths.
Quality of primary health care in China: challenges and recommendations
Authors: Xi Li, Harlan M Krumholz, Winnie Yip, Kar Keung Cheng, Jan De Maeseneer, Qingyue Meng, Elias Mossialos, Chuang Li, Jiapeng Lu, Meng Su, Qiuli Zhang, Dong Roman Xu, Liming Li, Sharon-Lise T Normand, Richard Peto, Jing Li, Zengwu Wang, Hongbing Yan, Runlin Gao, Somsak Chunharas, Xin Gao, Raniero Guerra, Huijie Ji, Yang Ke, Zhigang Pan, Xianping Wu, Shuiyuan Xiao, Xinying Xie, Yujuan Zhang, Jun Zhu, Shanzhu Zhu, Shengshou Hu
Journal: The Lancet (2020)
Development and validation of the immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma
Authors: Sai-Lan Liu, Li-Juan Bian, Ze-Xian Liu, Qiu-Yan Chen, Xue-Song Sun, Rui Sun, Dong-Hua Luo, Xiao-Yun Li, Bei-Bei Xiao, Jin-Jie Yan, Zi-Jian Lu, Shu-Mei Yan, Li Yuan, Lin-Quan Tang, Jian-Ming Li, Hai-Qiang Mai
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC). Methods Using multiplexed quantitative fluorescence, we detected 17 immune biomarkers in a primary screening cohort of 54 NPC tissues presenting with/without distant metastasis following radical therapy. The LASSO (least absolute shrinkage and selection operator) logistic regression model used statistically significant survival markers in the training cohort (n=194) to build an immune signature. The prognostic and predictive accuracy of it was validated in an external independent group of 304 patients. Results Eight statistically significant markers were identified in the screening cohort. The immune signature consisting of four immune markers (PD-L1+ CD163+, CXCR5, CD117) in intratumor was adopted to classify patients into high and low risk in the training cohort and it showed a high level of reproducibility between different batches of samples (r=0.988 for intratumor; p&lt;0.0001). High-risk patients had shorter distant metastasis-free survival (HR 5.608, 95% CI 2.619 to 12.006; p&lt;0.0001) and progression-free survival (HR 2.798, 95% CI 1.498 to 5.266; p=0·001). The C-indexes which reflected the predictive capacity in training and validation cohort were 0.703 and 0.636, respectively. Low-risk patients benefited from induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) (HR 0.355, 95% CI 0.147 to 0.857; p=0·021), while high-risk patients did not (HR 1.329, 95% CI 0.543 to 3.253; p=0·533). To predict the individual risk of distant metastasis, nomograms with the integration of both immune signature and clinicopathological risk factors were developed. Conclusions The immune signature provided a reliable estimate of distant metastasis risk in patients with NPC and might be applied to identify the cohort which benefit from IC+CCRT.
Evidence accumulation during perceptual decisions in humans varies as a function of dorsal frontoparietal organization
Authors: Méadhbh B. Brosnan, Kristina Sabaroedin, Tim Silk, Sila Genc, Daniel P. Newman, Gerard M. Loughnane, Alex Fornito, Redmond G. O’Connell, Mark A. Bellgrove
Journal: Nature Human Behaviour (2020)
Targeting self-assembly peptide for inhibiting breast tumor progression and metastasis
Authors: Shi Luo, Jiaxing Feng, Linyu Xiao, Ling Guo, Lang Deng, Zhengwu Du, Yuan Xue, Xu Song, Xun Sun, Zhirong Zhang, Yao Fu, Tao Gong
Journal: Biomaterials (2020)
Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study
Authors: Hin Chu, Jasper Fuk-Woo Chan, Terrence Tsz-Tai Yuen, Huiping Shuai, Shuofeng Yuan, Yixin Wang, Bingjie Hu, Cyril Chik-Yan Yip, Jessica Oi-Ling Tsang, Xiner Huang, Yue Chai, Dong Yang, Yuxin Hou, Kenn Ka-Heng Chik, Xi Zhang, Agnes Yim-Fong Fung, Hoi-Wah Tsoi, Jian-Piao Cai, Wan-Mui Chan, Jonathan Daniel Ip, Allen Wing-Ho Chu, Jie Zhou, David Christopher Lung, Kin-Hang Kok, Kelvin Kai-Wang To, Owen Tak-Yin Tsang, Kwok-Hung Chan, Kwok-Yung Yuen
Journal: The Lancet Microbe (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported from China in January, 2020. SARS-CoV-2 is efficiently transmitted from person to person and, in 2 months, has caused more than 82 000 laboratory-confirmed cases of coronavirus disease 2019 (COVID-19) and 2800 deaths in 46 countries. The total number of cases and deaths has surpassed that of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV). Although both COVID-19 and severe acute respiratory syndrome (SARS) manifest as pneumonia, COVID-19 is associated with apparently more efficient transmission, fewer cases of diarrhoea, increased mental confusion, and a lower crude fatality rate. However, the underlying virus-host interactive characteristics conferring these observations on transmissibility and clinical manifestations of COVID-19 remain unknown.
Toxicity in elderly breast cancer patients treated by a taxane based chemotherapy as adjuvant or neoadjuvant therapy for primary breast cancer
Authors: S. Loibl, G. Von Minckwitz, D. Elling, W. Janni, M. Kaufmann, S. Vescia, H. Eggemann, N. Harbeck, V. Nekljudova, S. Kuemmel
Journal: Journal of Clinical Oncology (2006)

18509 Background: Elderly patients (pts) are more likely to develop haematological toxicity with anthracycline based regimen. There are no sufficient data available on toxicities especially in elderly pts who are treated by taxane containing regimen. Methods: Four prospective randomised trials in the treatment of primary breast cancer have been combined retrospectively to evaluate the toxicity in pts ≥ 60 treated by a taxane. Pts received either 1: docetaxel/adriamycin/cyclophosphamide (TAC 75/50/600 mg/m 2 ), 2: adriamycin(epirubicin)/cyclophosphamide (A(E)/C: 60(90)/600 mgm 2 ) followed by docetaxel (T: 100 mg/m 2 ) or paclitaxel (P: 175mg/m 2 ), or 3: dose-dense adriamycin/docetaxel (AT dd: 50/75 mg/m 2 ) or 4: epirubicin-paclitaxel in sequence (E-P dd: 90–175 mg/m 2 ). A descriptive analysis was performed in regards to pts and per cycles. In the sequential regimen cycles without taxanes were not considered evaluable. Results: 917 pts median age of 64 (range 60–80) years were included in this pooled analysis. 59 were older than 70 years. In total 3852 cycles of a taxane containing chemotherapy were administered. 378 pts (41.2%) received therapy 1, 332 (36.2%) therapy 2, 121 (13.2%) therapy 3, and 86 (9.4%) therapy 4. A total of 16 % of the pts did not complete treatment. Grade 3–4 neutropenia occurred in 46.2% and febrile neutropenia in 6.1% of the pts, severe anemia (0.8%) and thrombopenia (1.1%) was infrequent. Main non hematological toxicities were (% pts with grade I-IV): fatigue 86; loss of appetite 74; nausea and vomiting 68; mucositis 60; sensory neuropathy; conjunctivitis 45; skin 38; nail 39; fluid retention 36; dyspnea 32. Conclusion: Toxicity of taxanes in pts older than 60 years does not significantly differ from younger pts. Therefore, taxanes as adjuvant or neoadjuvant treatment for primary breast cancer could also be considered in otherwise fit pts in the age group of 60–70. [Table: see text]
Covid-19: US governors call for government help to secure more tests
Authors: Janice Hopkins Tanne
Journal: BMJ (2020)

US governors have called on the federal government to help them get more covid-19 testing kits as well as personal protective equipment for healthcare workers after complaining that they were competing with each other and with the federal government to buy supplies in international markets.

President Donald Trump said at his press conference on 20 April that the states had enough tests but they just weren’t using them. He complained in a tweet that governors were asking for help when it was up to the states to take charge of testing.1

Experts said the US needed to greatly increase its testing capacity. A panel of economists, social scientists, lawyers, and ethicists said the US needed to conduct 20 million tests per day before the economy could fully re-open. The US has conducted 3.7 million …