tbuckley/cabot-search huggingface dataset:
Glucose oxidase-like activity of cerium oxide nanoparticles: use for personal glucose meter-based label-free target DNA detection
Authors: Hyo Yong Kim, Ki Soo Park, Hyun Gyu Park
Journal: Theranostics (2020)

Recently, personal glucose meter (PGM) has been utilized for the detection of non-glucose targets for point-of-care (POC) testing.Aimed at this goal, we herein developed a new PGM-based label-free read-out method for polymerase chain reaction (PCR) based on our novel finding that cerium oxide nanoparticles (CeO2 NPs) exhibit glucose oxidase-like activity comparable to the natural glucose oxidase enzyme.Methods: In principle, DNA amplicons produced by PCR in the presence of target DNA electrostatically bind to CeO2 NPs, leading to their aggregation and reducing the efficiency for CeO2 NP-catalyzed glucose oxidation reaction.Thus, glucose is hardly oxidized to gluconic acid, resulting in the maintenance of initial high glucose level.On the contrary, in the absence of target DNA or presence of non-target DNA, DNA amplicons are not produced and glucose is effectively oxidized by the glucose oxidase-like activity of CeO2 NPs, leading to the significant reduction of glucose level.Finally, the resulting glucose level is simply measured by using PGM.Results: With this strategy, DNA amplicons were quantitatively examined within 5 min, realizing ultrafast analysis of PCR results without any cumbersome and labor-intensive procedures.In addition, the target genomic DNA derived from Escherichia coli (E.coli) was sensitively determined down to 10 copies with high selectivity.Conclusion: Importantly, the use of PGM as a detection component enables its direct application in POC settings.Based on the meritorious features of PGM such as rapidity, simplicity, and cost-effectiveness, we expect that the devised system could serve as a core platform for the on-site read-out of PCR amplification.
Rationalization of emotion is also rational
Authors: Peter Railton
Journal: Behavioral and Brain Sciences (2020)

Abstract Cushman seeks to explain rationalization in terms of fundamental mental processes, and he hypotheses a selected-for function: information exchange between “rational” and “non-rational” processes in the brain. While this is plausible, his account overlooks the importance – and information value – of rationalizing the emotions of ourselves and others. Incorporating such rationalization would help explain the effectiveness of rationalization and its connection with valuation, as well as raise a challenge to his way of bifurcating “rational” and “non-rational” processes.
Prospective registration and reporting of trial number in randomised clinical trials: global cross sectional study of the adoption of ICMJE and Declaration of Helsinki recommendations
Authors: Mustafa Al-Durra, Robert P Nolan, Emily Seto, Joseph A Cafazzo
Journal: BMJ (2020)

To evaluate the compliance with prospective registration and inclusion of the trial registration number (TRN) in published randomised controlled trials (RCTs), and to analyse the rationale behind, and detect selective registration bias in, retrospective trial registration.Cross sectional analysis.PubMed, the 17 World Health Organization's trial registries, University of Toronto library, International Committee of Medical Journal Editors (ICMJE) list of member journals, and the InCites Journal Citation Reports.RCTs registered in any WHO trial registry and published in any PubMed indexed journal in 2018.This study included 10 500 manuscripts published in 2105 journals. Overall, 71.2% (7473/10500) reported the TRN and 41.7% (3013/7218) complied with prospective trial registration. The univariable and multivariable analyses reported significant relations (P<0.05) between reporting the TRN and the impact factor and ICMJE membership of the publishing journal. A significant relation (P<0.05) was also observed between prospective trial registration and the registry, region, condition, funding, trial size, interval between paper registration and submission dates, impact factor, and ICMJE membership of the publishing journal. A manuscript published in an ICMJE member journal was 5.8 times more likely to include the TRN (odds ratio 5.8, 95% confidence interval 4.0 to 8.2), and a published trial was 1.8 times more likely to be registered prospectively (1.8, 1.5 to 2.2) when published in an ICMJE member journal compared with other journals. This study detected a new form of bias, selective registration bias, with a higher proportion (85.2% (616/723)) of trials registered retrospectively within a year of submission for publication. Higher rates of retrospective registrations were observed within the first three to eight weeks after enrolment of study participants. Within the 286 RCTs registered retrospectively and published in an ICMJE member journal, only 2.8% (8/286) of the authors included a statement justifying the delayed registration. Reasons included lack of awareness, error of omission, and the registration process taking longer than anticipated.This study found a high compliance in reporting of the TRN for trial papers published in ICMJE member journals, but prospective trial registration was low.
GMC as bogeyman: the rule of law has broken down in medicine
Authors: Gabrielle Pendlebury
Journal: BMJ (2020)

Gerada says the General Medical Council is the bogeyman,1 but I think the legal process is.

The rule of law is defined in the Oxford English Dictionary as, “The authority and influence of law in society, especially when viewed as a constraint on individual and institutional behaviour; (hence) the principle …
Abstract 12176: Human-Like Cmah Loss Aggravates Inflammation- and Age-Mediated Cardiac Dysfunction in Mice
Authors: Jonathan Okerblom, Alice E Zemljic-Harpf, Marianne P Thio, Yasuhiro Ichikawa, David M Roth, Ajit Varki, Hemal H Patel
Journal: Circulation (2018)

Introduction: Congestive heart failure (CHF) is an increasing clinical problem leading to mortality that is typically a disease of the aged heart in humans. Molecular mechanisms and therapeutics ha...
Abstract 14334: Postpartum Depression: A Novel Predictor of Cardiovascular Disease Risk in Women
Authors: Punag Divanji, Diana Divanji, Rima Arnaout, Michelle Albert, Elissa Epel, Gregory Nah, Nisha I Parikh
Journal: Circulation (2018)

Introduction: Whereas major depression is a recognized risk factor for cardiovascular disease (CVD), it is uncertain whether postpartum depression (PPD) is also associated with CVD in women. Method...
Commensal Bacteria Modulate Immunoglobulin A Binding in Response to Host Nutrition
Authors: Kelsey E. Huus, Kylynda C. Bauer, Eric M. Brown, Tahereh Bozorgmehr, Sarah E. Woodward, Antonio Serapio-Palacios, Rozlyn C.T. Boutin, Charisse Petersen, B. Brett Finlay
Journal: Cell Host & Microbe (2020)
JSCO—ESMO—ASCO—JSMO—TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions
Authors: T. Yoshino, G. Pentheroudakis, S. Mishima, M.J. Overman, K.-H. Yeh, E. Baba, Y. Naito, F. Calvo, A. Saxena, L.-T. Chen, M. Takeda, A. Cervantes, H. Taniguchi, K. Yoshida, Y. Kodera, Y. Kitagawa, J. Tabernero, H. Burris, J.-Y. Douillard
Journal: Annals of Oncology (2020)

A Japan Society of Clinical Oncology (JSCO)-hosted expert meeting was held in Japan on 27 October 2019, which comprised experts from the JSCO, the Japanese Society of Medical Oncology (JSMO), the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the Taiwan Oncology Society (TOS). The purpose of the meeting was to focus on what we have learnt from both microsatellite instability (MSI)/deficient mismatch repair (dMMR) biomarkers in predicting the efficacy of anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy, and the neurotrophic tyrosine receptor kinase (NTRK) gene fusions in predicting the efficacy of inhibitors of the tropomyosin receptor kinase (TRK) proteins across a range of solid tumour types. The recent regulatory approvals of the anti-PD-1 antibody pembrolizumab and the TRK inhibitors larotrectinib and entrectinib, based on specific tumour biomarkers rather than specific tumour type, have heralded a paradigm shift in cancer treatment approaches. The purpose of the meeting was to develop international expert consensus recommendations on the use of such tumour-agnostic treatments in patients with solid tumours. The aim was to generate a reference document for clinical practice, for pharmaceutical companies in the design of clinical trials, for ethics committees in the approval of clinical trial protocols and for regulatory authorities in relation to drug approvals, with a particular emphasis on diagnostic testing and patient selection.
Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study
Authors: Rong-Hui Du, Li-Rong Liang, Cheng-Qing Yang, Wen Wang, Tan-Ze Cao, Ming Li, Guang-Yun Guo, Juan Du, Chun-Lan Zheng, Qi Zhu, Ming Hu, Xu-Yan Li, Peng Peng, Huan-Zhong Shi
Journal: European Respiratory Journal (2020)

The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.146–17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755–8.044; p=0.007), CD3+CD8+ T-cells ≤75 cells·μL−1 (OR 3.982, 95% CI 1.132–14.006; p<0.001) and cardiac troponin I ≥0.05 ng·mL−1 (OR 4.077, 95% CI 1.166–14.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia.” has been corrected to: “Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.201−11.803; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 1.279−4.747; p=0.007), CD3+CD8+ T-cells ≤75 cells·μL−1 (OR 3.982, 95% CI 1.761–9.004; p<0.001) and cardiac troponin I ≥0.05 ng·mL−1 (OR 4.077, 95% CI 1.778–9.349; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia. In a sex-, age- and comorbid illness-matched case-control study, CD3+CD8+ T-cells ≤75 cells·μL-1 and cardiac troponin I ≥0.05 ng·mL-1 remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL-1 and cardiac troponin I ≥0.05 ng·mL-1 The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.
Geographic Differences in COVID-19 Cases, Deaths, and Incidence — United States, February 12–April 7, 2020
Authors: Stephanie Bialek, Virginia Bowen, Nancy Chow, Aaron Curns, Ryan Gierke, Aron Hall, Michelle Hughes, Tamara Pilishvili, Matthew Ritchey, Katherine Roguski, Benjamin Silk, Tami Skoff, Preethi Sundararaman, Emily Ussery, Michael Vasser, Hilary Whitham, John Wen
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Community transmission of coronavirus disease 2019 (COVID-19) was first detected in the United States in February 2020. By mid-March, all 50 states, the District of Columbia (DC), New York City (NYC), and four U.S. territories had reported cases of COVID-19. This report describes the geographic distribution of laboratory-confirmed COVID-19 cases and related deaths reported by each U.S. state, each territory and freely associated state,* DC, and NYC during February 12-April 7, 2020, and estimates cumulative incidence for each jurisdiction. In addition, it projects the jurisdiction-level trajectory of this pandemic by estimating case doubling times on April 7 and changes in cumulative incidence during the most recent 7-day period (March 31-April 7). As of April 7, 2020, a total of 395,926 cases of COVID-19, including 12,757 related deaths, were reported in the United States. Cumulative COVID-19 incidence varied substantially by jurisdiction, ranging from 20.6 cases per 100,000 in Minnesota to 915.3 in NYC. On April 7, national case doubling time was approximately 6.5 days, although this ranged from 5.5 to 8.0 days in the 10 jurisdictions reporting the most cases. Absolute change in cumulative incidence during March 31-April 7 also varied widely, ranging from an increase of 8.3 cases per 100,000 in Minnesota to 418.0 in NYC. Geographic differences in numbers of COVID-19 cases and deaths, cumulative incidence, and changes in incidence likely reflect a combination of jurisdiction-specific epidemiologic and population-level factors, including 1) the timing of COVID-19 introductions; 2) population density; 3) age distribution and prevalence of underlying medical conditions among COVID-19 patients (1-3); 4) the timing and extent of community mitigation measures; 5) diagnostic testing capacity; and 6) public health reporting practices. Monitoring jurisdiction-level numbers of COVID-19 cases, deaths, and changes in incidence is critical for understanding community risk and making decisions about community mitigation, including social distancing, and strategic health care resource allocation.
Abstract 10133: Incorporation of Biomarkers into Risk Assessment for Allocation of Antihypertensive Medication According to the 2017 Acc/aha High Blood Pressure Guideline: A Pooled Cohort Analysis
Authors: Ambarish Pandey, Kershaw Patel, Wanpen Vongpatanasin, Colby Ayers, Jarett D Berry, Robert J Mentz, Michael J Blaha, Paul Muntner, Muthiah Vaduganathan, Adolfo Correa, Javed Butler, Daichi Shimbo, Vijay Nambi, John W McEvoy, Christopher Defilippi, Stephen L Seliger, Christie M Ballantyne, James A De Lemos, Parag H Joshi
Journal: Circulation (2019)

Introduction: The 2017 ACC/AHA BP guideline incorporates ASCVD risk to guide BP treatment. Whether biomarkers of cardiac injury and stress could inform risk assessment and BP treatment decisions is...
Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program
Authors: John W Walker, Celeste Lebbé, Giovanni Grignani, Paul Nathan, Luc Dirix, Eyal Fenig, Paolo Antonio Ascierto, Shahneen Sandhu, Rodrigo Munhoz, Elena Benincasa, Sarah Flaskett, Josh Reed, Arne Engelsberg, Subramanian Hariharan, Vijay Kasturi
Journal: Journal for ImmunoTherapy of Cancer (2020)

Avelumab, a human anti-programmed death-ligand 1 immunoglobulin G1 monoclonal antibody, showed favorable efficacy and safety in patients with metastatic Merkel cell carcinoma (mMCC) in the phase II JAVELIN Merkel 200 trial, leading to approval in multiple countries. We describe real-world experience with avelumab in patients with mMCC from an expanded access program.Eligible patients had mMCC and progressive disease during or after chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received an initial 3-month supply of avelumab (administered as 10 mg/kg intravenously every 2 weeks until progressive disease or unacceptable toxicity); resupply was allowed following complete response, partial response, stable disease, or clinical benefit per physician assessment.Between December 15, 2015, and March 4, 2019, 558 of 620 requests from 38 countries were medically approved, and 494 patients received avelumab. Among 240 evaluable patients, the objective response rate was 46.7% (complete response in 22.9%, including 3 of 16 potentially immunocompromised patients), and the disease control rate was 71.2%. The median duration of treatment in evaluable patients with response was 7.9 months (range, 1.0-41.7) overall and 5.2 months (range, 3.0-13.9) in immunocompromised patients. No new safety signals were identified. The expanded access program closed for new requests on December 31, 2018, as required after regulatory approval; benefitting patients continued to receive avelumab.The avelumab expanded access program for patients with mMCC demonstrated efficacy and safety in a real-world setting, consistent with the results from JAVELIN Merkel 200, and provided a treatment for patients with limited options.
Rationalization is rare, reasoning is pervasive
Authors: Audun Dahl, Talia Waltzer
Journal: Behavioral and Brain Sciences (2020)

Abstract If rationalization were ubiquitous, it would undermine a fundamental premise of human discourse. A review of key evidence indicates that rationalization is rare and confined to choices among comparable options. In contrast, reasoning is pervasive in human decision making. Within the constraints of reasoning, rationalization may operate in ambiguous situations. Studying these processes requires careful definitions and operationalizations.
Association of Grandparental and Parental Age at Childbirth With Autism Spectrum Disorder in Children
Authors: Yu Gao, Yongfu Yu, Jingyuan Xiao, Jiajun Luo, Yawei Zhang, Ying Tian, Jun Zhang, Jørn Olsen, Jiong Li, Zeyan Liew
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Advanced parental age has been associated with autism spectrum disorders (ASDs) in children. However, little is known about the association between grandparental age at the time of birth of the parent and the risk of ASD in the grandchildren. <h3>Objective</h3> To estimate the associations between parental and grandparental age and ASD risk in children. <h3>Design, Setting, and Participants</h3> This population-based, multigenerational cohort study used data from Danish national health registries. A parental age cohort was constructed to evaluate the association between parental age and ASD in 1 476 783 singleton children born from 1990 to 2013, and a multigenerational cohort was also constructed including 362 438 fathers and 458 234 mothers born from 1973 to 1990 for whom information on grandparental age was available. Data analyses were conducted from November 1, 2018, through February 7, 2020. <h3>Exposures</h3> Parental age at childbirth and grandparental age at the time of the birth of the parent. <h3>Main Outcomes and Measures</h3> Diagnoses of ASD in children were obtained from the Danish Psychiatric Central Register (1994-2017). Logistic regression analysis was used to estimate the associations between parental or grandparental age and ASD in children. <h3>Results</h3> Of the 1 476 783 children born from 1990 to 2013, 758 066 (51.3%) were male, and 27 616 (1.9%) had ASD (20 467 [74.1%] were male). Advanced paternal or maternal age over 30 years was monotonically associated with increased ASD risk, with odds ratios (ORs) of 1.56 (95% CI, 1.45-1.68) for maternal age 40 years and older and 1.57 (95% CI, 1.39-1.78) for paternal age 50 years and older, compared with parents aged 25 to 29 years. In the multigenerational cohort, 9364 grandchildren (1.7%) had ASD. This study found U-shaped associations, in that ASD risk was higher among grandchildren of younger (≤19 years) maternal grandmothers (OR, 1.68; 95% CI, 1.52-1.85), younger maternal grandfathers (OR, 1.50; 95% CI, 1.26-1.78), and younger paternal grandmothers (OR, 1.18; 95% CI, 1.04-1.34), and older (≥40 years) paternal grandmothers (OR, 1.40; 95% CI, 1.03-1.90) compared with the grandchildren of grandparents who were aged 25 to 29 years at the time of giving birth to the parents. <h3>Conclusions and Relevance</h3> These findings corroborate previous studies suggesting that advanced parental age is independently associated with increased ASD risk in children. This study also found that children with young maternal grandparents and children with young and old paternal grandparents had elevated ASD risk. Possible transmission of ASD risk across generations should be considered in etiological research on ASD.
Bioactive phospho-therapy with black phosphorus for <i>in vivo</i> tumor suppression
Authors: Shengyong Geng, Ting Pan, Wenhua Zhou, Haodong Cui, Lie Wu, Zhibin Li, Paul K. Chu, Xue-Feng Yu
Journal: Theranostics (2020)

Background and Purpose: Although inorganic nanomaterials have been widely used in multimodal cancer therapies, the intrinsic contributions of the materials are not well understood and sometimes underestimated.In this work, bioactive phospho-therapy with black phosphorus nanosheets (BPs) for in vivo tumor suppression is studied.Methods: Orthotopic liver tumor and acute myeloid leukemia are chosen as the models for the solid tumor and hematological tumor, respectively.BPs are injected into mice through the tail vein and tumor growth is monitored by IVIS bioluminescence imaging.Tumor tissues and serum samples are collected to determine the suppression effect and biosafety of BPs after treatment. Results:The in vitro studies show that BPs with high intracellular uptake produce apoptosis-and autophagy-mediated programmed cell death of human liver carcinoma cells but do not affect normal cells.BPs passively accumulate in the tumor site at a high concentration and inhibit tumor growth.The tumor weight is much less than that observed from the doxorubicin (DOX)-treated group.The average survival time is extended by at least two months and the survival rate is 100% after 120 days.Western bolt analysis confirms that BPs suppress carcinoma growth via the apoptosis and autophagy pathways.In addition, administration of BPs into mice suffering from leukemia results in tumor suppression and long survival.Conclusions: This study reveals that BPs constitute a type of bioactive anti-cancer agents and provides insights into the application of inorganic nanomaterials to cancer therapy.
Anleitung zur Diagnose und Therapie der Kehlkopf, Nasen und Ohrenkrankheiten.
Journal: JAMA (1923)

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Secretory proteostasis of the retinal pigmented epithelium: Impairment links to age-related macular degeneration
Authors: Luminita Paraoan, Umar Sharif, Emil Carlsson, Wasu Supharattanasitthi, Nur Musfirah Mahmud, Tengku Ain Kamalden, Paul Hiscott, Malcolm Jackson, Ian Grierson
Journal: Progress in Retinal and Eye Research (2020)