tbuckley/cabot-search huggingface dataset:
Diagnostic Testing for Severe Acute Respiratory Syndrome–Related Coronavirus 2
Authors: Matthew P. Cheng, Jesse Papenburg, Michaël Desjardins, Sanjat Kanjilal, Caroline Quach, Michael Libman, Sabine Dittrich, Cedric P. Yansouni
Journal: Annals of Internal Medicine (2020)

Diagnostic testing to identify persons infected with severe acute respiratory syndrome–related coronavirus 2 (SARS-CoV-2) infection is central to control the global pandemic of COVID-19 that began in late 2019. In a few countries, the use of diagnostic testing on a massive scale has been a cornerstone of successful containment strategies. In contrast, the United States, hampered by limited testing capacity, has prioritized testing for specific groups of persons. Real-time reverse transcriptase polymerase chain reaction–based assays performed in a laboratory on respiratory specimens are the reference standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging. Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as in the accurate determination of live viral shedding during convalescence to inform decisions to end isolation. Many affluent countries have encountered challenges in test delivery and specimen collection that have inhibited rapid increases in testing capacity. These challenges may be even greater in low-resource settings. Urgent clinical and public health needs currently drive an unprecedented global effort to increase testing capacity for SARS-CoV-2 infection. Here, the authors review the current array of tests for SARS-CoV-2, highlight gaps in current diagnostic capacity, and propose potential solutions.
Abstract 10273: Bacteroides Protect Against Atherosclerosis by Regulating Gut Microbial Lipopolysaccharide Production
Authors: Naofumi Yoshida, Tomoya Yamashita, Takuo Emoto, Tokiko Tabata, Yoshihiro Saito, Hikaru Watanabe, Takuji Yamada, Ken-ichi Hirata
Journal: Circulation (2019)

Introduction: Increasing evidence has suggested that a strong correlation exists between the gut microbiota and development of coronary artery disease (CAD). However, how specific gut bacteria cont...
(H)Elping nerve growth factor: Elp1 inhibits TrkA’s phosphatase to maintain retrograde signaling
Authors: David R. Kaplan, William C. Mobley
Journal: Journal of Clinical Investigation (2020)

Nerve growth factor (NGF) regulates many aspects of neuronal biology by retrogradely propagating signals along axons to the targets of those axons. How this occurs when axons contain a plethora of proteins that can silence those signals has long perplexed the neurotrophin field. In this issue of the JCI, Li et al. suggest an answer to this vexing problem, while exploring why the Elp1 gene that is mutated in familial dysautonomia (FD) causes peripheral neuropathy. They describe a distinctive function of Elp1 as a protein that is required to sustain NGF signaling by blocking the activity of its phosphatase that shuts off those signals. This finding helps explain the innervation deficits prominent in FD and reveals a unique role for Elp1 in the regulation of NGF-dependent TrkA activity.
Estimated Prevalence of Nonverbal Learning Disability Among North American Children and Adolescents
Authors: Amy E. Margolis, Jessica Broitman, John M. Davis, Lindsay Alexander, Ava Hamilton, Zhijie Liao, Sarah Banker, Lauren Thomas, Bruce Ramphal, Giovanni A. Salum, Kathleen Merikangas, Jeff Goldsmith, Tomas Paus, Katherine Keyes, Michael P. Milham
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial processing but not in reading or verbal ability; in addition, problems in math calculation, visual executive functioning, fine-motor skills, and social skills are often present. To our knowledge, there are no population-based estimates of the prevalence of NVLD in community samples. <h3>Objective</h3> To estimate the prevalence of the NVLD cognitive profile in 3 independent samples of children and adolescents from studies centered around brain imaging in the US and Canada. <h3>Design, Setting, and Participants</h3> This cross-sectional study used data from 2 samples recruited from the community and overselected for children with psychiatric disorders (Healthy Brain Network [HBN], January 1, 2015, to December 31, 2019, and Nathan Kline Institute–Rockland Sample [NKI], January 1, 2011, to December 31, 2018) and 1 community-ascertained population sample (Saguenay Youth Study [SYS], January 1, 2003, to December 31, 2012) overselected for active maternal smoking during pregnancy. <h3>Main Outcomes and Measures</h3> Prevalence of NVLD. Criteria for NVLD were based on clinical records of deficits in visual-spatial reasoning and impairment in 2 of 4 domains of function (fine-motor skills, math calculation, visual executive functioning, and social skills). Sample weighting procedures adjusted for demographic differences in sample frequencies compared with underlying target populations. Inflation factor weights accounted for overrepresentation of psychiatric disorders (HBN and NKI samples). <h3>Results</h3> Across 3 independent samples, the prevalence of NVLD was estimated among 2596 children and adolescents aged 6 to 19 years (mean [SD] age, 12.5 [3.4] years; 1449 male [55.8%]). After sample and inflation weights were applied, the prevalence of NVLD was 2.78% (95% CI, 2.03%-3.52%) in the HBN sample and 3.9% (95% CI, 1.96%-5.78%) in the NKI sample. In the SYS sample, the prevalence of NVLD was 3.10% (95% CI, 1.93%-4.27%) after applying the sample weight. Across samples and estimation strategies, the population prevalence of NVLD was estimated to range from 3% to 4%. When applied to the US population younger than 18 years, 2.2 million to 2.9 million children and adolescents were estimated to have NVLD. <h3>Conclusions and Relevance</h3> The findings suggest that the prevalence of NVLD in children and adolescents may be 3% to 4%. Given that few youths are diagnosed with NVLD and receive treatment, increased awareness, identification of the underlying neurobiological mechanisms, and development and testing interventions for the disorder are needed.
I feel I am missing a piece of the puzzle
Authors: Rhiann Johns
Journal: BMJ (2020)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following I feel I am missing a piece of the puzzle Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
The WW domains dictate isoform-specific regulation of YAP1 stability and pancreatic cancer cell malignancy
Authors: Qiang Guo, Meiyu Quan, Jinglai Dong, Jing Bai, Jie Wang, Rui Han, Wei Wang, Yaxin Cai, Yu-Qing Lv, Qianjie Chen, Huijing Xu, Han-Deng Lyu, Liancheng Deng, Depu Zhou, Xueyuan Xiao, Stijn De Langhe, Daniel D Billadeau, Zhenkun Lou, Jin-San Zhang
Journal: Theranostics (2020)

YAP1 is a key mediator of the Hippo pathway capable of exerting a profound effect on organ size as well as tumorigenesis. Alternative mRNA splicing of human YAP1 results in at least 8 protein isoforms that differ within the 2nd WW motif and the transcriptional activation domain. Methods: To investigate the isoform-specific differences in their mRNA expression, transcriptional activity and tumor-promoting function, we cloned cDNA encoding all of the eight YAP1 protein isoforms. Then, we examined their mRNA expression, subcellular localization, transcriptional regulation properties, interactions with key regulatory partners, and protein stability in response to changes in cell density, as well as their effects on pancreatic cancer cell malignancy both in vitro and in vivo. Results: Multiple YAP1 mRNA isoforms are expressed in commonly used pancreatic cancer lines as well as human pancreatic cancer PDX lines. Based on the analysis of heterologous reporter and endogenous target genes, all YAP1 isoforms are capable of activating transcription, albeit to a different extent. Importantly, we unveiled a marked discrepancy between the mRNA and protein expression levels of the YAP1-1 and YAP1-2 isoforms. We further discovered that the YAP1-2 isoform, which contains two tandem WW motifs, is less stable at the protein level, particularly at high cell densities. Mechanistically, we found that the presence of the 2nd WW motif in YAP1-2 facilitates the de novo formation of the YAP1-2/AMOT/LATS1 complex and contributes to a stronger binding of YAP1-2 to LATS1 and subsequently increased YAP1-2 ubiquitination and degradation by β-TRCP. Conclusion: Our data reveals a potent effect of YAP1-1 on pancreatic cancer malignancy in vitro and in vivo and provides novel mechanistic insight into isoform-specific and cell density-dependent regulation of YAP1 stability, as well as its impact on cancer malignancy.
Abstract P160: Cross-sectional and Longitudinal Associations of Objective Sedentary Time, Physical Activity, and Obesity: The CARDIA Study
Authors: Bethany Barone Gibbs, Mercedes Carnethon, Tiffany Gary-Webb, John Jakicic, Kelley Pettee Gabriel, Jamal Rana, Jared Reis, Barbara Sternfeld, Cora Lewis
Journal: Circulation (2016)

Higher sedentary time (ST) and lower moderate-to-vigorous intensity physical activity (MVPA) have been independently associated with obesity, but most available studies are cross-sectional and measure ST and MVPA by self-report. It has also been suggested that obesity may predict future ST rather than ST leading to future obesity. Objective: To investigate whether objective ST and MVPA were associated with current and 5-year changes in body mass index (BMI) and waist circumference (WC). Methods: We analyzed 1,963 CARDIA participants (aged 38-50 years, 57% female, 41% black) with accelerometry data (≥4 days with ≥10 hr/day) in 2005-2006. BMI and WC were assessed concurrently and 5 years later. Linear regression evaluated cross-sectional and longitudinal associations between ST and MVPA with BMI and WC across all participants and in race/gender groups due to the presence of interactions. Standardized coefficients (β std ) reflect differences per each 1.7 hr/day increase in ST and each time MVPA increases by a factor of 2. Results: Average ST was 8.1 ± 1.7 hr/day and 21% met MVPA guidelines of 150 min/wk. During the 5 year follow-up, BMI and WC increased in all groups (Table, all p&lt;0.01). Cross-sectionally, in the combined cohort, higher ST and lower MVPA were each independently related to higher BMI and WC (Table). After stratification, lower MVPA was associated with higher BMI in white women and higher WC in white women and men. Higher ST was directly related to BMI in black men and WC in white and black men. Baseline ST and MVPA did not predict 5-year changes in BMI or WC in the full cohort; higher MVPA predicted a smaller BMI increase only in white men (Table). Conclusions: ST and MVPA were each associated with general and abdominal obesity cross-sectionally, but mostly did not predict 5-year changes in these outcomes. These findings do not support that lower ST and higher MVPA will curtail unfavorable gains in general and abdominal obesity over 5 years, but could result from a relationship where greater obesity leads to higher ST and inactivity.
Advance Care Planning and “The Love Song of J. Alfred Prufrock”
Authors: Daniel P. Sulmasy
Journal: JAMA Internal Medicine (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 Access Provided by KOSIN UNIVERSITY MEDICAL LIBRARY JAMA Internal Medicine 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 Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology
Authors: Jose de Leon, Can-Jun Ruan, Georgios Schoretsanitis, Carlos De las Cuevas
Journal: Psychotherapy and Psychosomatics (2020)

Using Richardson and Davidson’s model and the sciences of pharmacokinetics and clinical pharmacopsychology, this article reviewed the: (1) poor life expectancy associated with treatment-resistant schizophrenia (TRS), which may be improved in patients who adhere to clozapine; (2) findings that clozapine is the best treatment for TRS (according to efficacy, effectiveness and well-being); and (3) potential for clozapine to cause vulnerabilities, including potentially lethal adverse drug reactions such as agranulocytosis, pneumonia, and myocarditis. Rational use requires: (1) modification of the clozapine package insert worldwide to include lower doses for Asians and to avoid the lethality associated with pneumonia, (2) the use of clozapine levels for personalizing dosing, and (3) the use of slow and personalized titration. This may make clozapine as safe as possible and contribute to increased life expectancy and well-being. In the absence of data on COVID-19 in clozapine patients, clozapine possibly impairs immunological mechanisms and may increase pneumonia risk in infected patients. Psychiatrists should call their clozapine patients and families and explain to them that if the patient develops fever or flu-like symptoms, the psychiatrist should be called and should consider halving the clozapine dose. If the patient is hospitalized with pneumonia, the treating physician needs to assess for symptoms of clozapine intoxication since halving the dose may not be enough for all patients; consider decreasing it to one-third or even stopping it. Once the signs of inflammation and fever have disappeared, the clozapine dose can be slowly increased to the prior dosage level.
Clinical features and survival of multiple myeloma patients harboring t(14;16) in the era of novel agents
Authors: Roberto Mina, Nisha S. Joseph, Francesca Gay, Efstathios Kastritis, Maria Teresa Petrucci, Jonathan L. Kaufman, Vittorio Montefusco, Maria Gavriatopoulou, Francesca Patriarca, Paola Omedé, Lawrence H. Boise, Maria Roussou, Nicola Giuliani, Stefania Oliva, Massimo Offidani, Angelo Belotti, David L. Jaye, Lorenzo De Paoli, Evangelos Terpos, Sagar Lonial, Mario Boccadoro, Ajay K. Nooka, Meletios A. Dimopoulos
Journal: Blood Cancer Journal (2020)
Efficacy and safety of rivaroxaban plus aspirin in women and men with chronic coronary or peripheral artery disease
Authors: Yan Liang, Jun Zhu, Lisheng Liu, Sonia S Anand, Stuart J Connolly, Jackie Bosch, Tomasz J Guzik, Martin O’Donnell, Gilles R Dagenais, Keith Aa Fox, Olga Shestakovska, Scott D Berkowitz, Eva Muehlhofer, Lars Keller, Salim Yusuf, John W Eikelboom
Journal: Cardiovascular Research (2020)

The COMPASS trial demonstrated that the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease or peripheral artery disease by 24% during a mean follow-up of 23 months. We explored whether this effect varies by sex.The effects were examined in women and men using log-rank tests and Kaplan-Meier curve. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were obtained from stratified Cox proportional hazards models to explore subgroup effects including subgroup of women and men according to baseline modified REACH risk score. Of 27 395 patients randomized, 18 278 were allocated to receive rivaroxaban plus aspirin (n = 9152) or aspirin alone (n = 9126), and of these, 22.1% were women. Women compared with men had similar incidence rates for MACE and major bleeding but borderline lower rates for myocardial infarction (1.7% vs. 2.2%, P = 0.05). The effect of combination therapy compared with aspirin in women and men was consistent for MACE (women: 3.8% vs. 5.2%, HR 0.72, 95% CI 0.54-0.97; men: 4.2% vs. 5.5%, HR 0.76, 95% CI 0.66-0.89; P interaction 0.75) and major bleeding (women: 3.1% vs. 1.4%, HR 2.22, 95% CI 1.42-3.46; men: 3.2% vs. 2.0%, HR 1.60, 95% CI 1.29-1.97; P interaction 0.19). There was no significant interaction between randomized treatment and baseline modified REACH score above or below the median for MACE or major bleeding.In patients with stable coronary artery disease or peripheral artery disease, the combination of rivaroxaban (2.5 mg twice daily) and aspirin compared with aspirin alone appears to produce consistent benefits in women and men, independent of baseline cardiovascular risk.
Intervention study to evaluate the importance of information given to patients with contact allergy: a randomized, investigator‐blinded clinical trial*
Authors: A. Dizdarevic, W. Troensegaard, A. Uldahl, O. Bergendorff, I. Siemund, Å. Svensson, A. Sonesson
Journal: British Journal of Dermatology (2020)

In contact dermatitis, it is crucial to understand and remember the outcome of patch testing. Unfortunately, many patients do not remember the results of their patch tests. Our aim was to evaluate the effects of an intervention programme in which extensive information on specific contact allergy was provided, in individuals with positive patch test reactions. The study was designed as a randomized, investigator‐blinded clinical trial. Participants with positive test reactions were randomized into two groups that received either standard information according to clinical routine or standard information and a reminder letter. Knowledge of contact allergies was evaluated using questionnaires 12 months after inclusion. There were 184 adults included in the trial and the response rate at 1‐year follow‐up was 78% (143 of 184). Sixty‐five per cent (45 of 69) in the intervention group and 54% (40 of 74) in the control group reported the correct name of the allergen (P = 0·23). Participants with several – as opposed to few – positive patch test reactions had difficulty in remembering the correct names of the allergens (P = 0·001). Moreover, the type of allergy had an influence on their ability to remember the name of the allergen correctly and their ability to make changes in lifestyle. The intervention performed did not significantly affect the participants’ ability to remember their contact allergy. To achieve better knowledge and changes in lifestyle, efforts to inform should concentrate on individuals with several positive patch test reactions, those with particular allergens, individuals over 60 years of age, and – concerning changes in lifestyle – males.
Abstract 11950: Predictive Ability of Machine Learning Models for High-Grade Coronary Artery Disease Using Free Fatty-Acid Metabolites
Authors: Raymond O McCubrey, Viet T Le, Jeramie Watrous, Mahan Najhawan, Khoi Dao, Benjamin D Horne, Jeffrey L Anderson, Kirk U Knowlton, Mohit Jain, Stacey Knight
Journal: Circulation (2019)

Introduction: Non-invasive methods for assessing risk of high-grade obstructive coronary artery disease (CAD) may be an effective way to reduce unnecessary procedures, possible complications, and h...
Selective targeting of the oncogenic <i>KRAS</i> G12S mutant allele by CRISPR/Cas9 induces efficient tumor regression
Authors: Qianqian Gao, Wenjie Ouyang, Bin Kang, Xu Han, Ying Xiong, Renpeng Ding, Yijian Li, Fei Wang, Lei Huang, Lei Chen, Dan Wang, Xuan Dong, Zhao Zhang, Yanshan Li, Baichen Ze, Yong Hou, Huanming Yang, Yuanyuan Ma, Ying Gu, Cheng-Chi Chao
Journal: Theranostics (2020)

Rationale: KRAS is one of the most frequently mutated oncogenes in cancers.The protein's picomolar affinity for GTP/GDP and smooth protein structure resulting in the absence of known allosteric regulatory sites makes its genomic-level activating mutations a difficult but attractive target.Methods: Two CRISPR systems, genome-editing CRISPR/SpCas9 and transcription-regulating dCas9-KRAB, were developed to deplete the KRAS G12S mutant allele or repress its transcription, respectively, with the goal of treating KRAS-driven cancers.Results: SpCas9 and dCas9-KRAB systems with a sgRNA targeting the mutant allele blocked the expression of the mutant KRAS gene, leading to an inhibition of cancer cell proliferation.Local adenoviral injections using SpCas9 and dCas9-KRAB systems suppressed tumor growth in vivo.The gene-depletion system (SpCas9) performed more effectively than the transcription-suppressing system (dCas9-KRAB) on tumor inhibition.Application of both Cas9 systems to wild-type KRAS tumors did not affect cell proliferation.Furthermore, through bioinformatic analysis of 31555 SNP mutations of the top 20 cancer driver genes, the data showed that our mutant-specific editing strategy could be extended to a reference list of oncogenic mutations with high editing potentials.This pipeline could be applied to analyze the distribution of PAM sequences and survey the best alternative targets for gene editing. Conclusion:We successfully developed both gene-depletion and transcription-suppressing systems to specifically target an oncogenic KRAS mutant allele that led to significant tumor regression.These findings show the potential of CRISPR-based strategies for the treatment of tumors with driver gene mutations.
3D approaches to model the tumor microenvironment of pancreatic cancer
Authors: Elena Tomás-Bort, Markus Kieler, Shreya Sharma, Juliana B Candido, Daniela Loessner
Journal: Theranostics (2020)

In tumor engineering, 3D approaches are used to model components of the tumor microenvironment and to test new treatments.Pancreatic cancers are a cancer of substantial unmet need and survival rates are lower compared to any other cancer.Bioengineering techniques are increasingly applied to understand the unique biology of pancreatic tumors and to design patient-specific models.Here we summarize how extracellular and cellular elements of the pancreatic tumor microenvironment and their interactions have been studied in 3D cell cultures.We review selected clinical trials, assess the benefits of therapies interfering with the tumor microenvironment and address their limitations and future perspectives.