tbuckley/cabot-search huggingface dataset:
Benchmarking principal component analysis for large-scale single-cell RNA-sequencing
Authors: Koki Tsuyuzaki, Hiroyuki Sato, Kenta Sato, Itoshi Nikaido
Journal: Genome biology (2020)

Abstract Background Principal component analysis (PCA) is an essential method for analyzing single-cell RNA-seq (scRNA-seq) datasets, but for large-scale scRNA-seq datasets, computation time is long and consumes large amounts of memory. Results In this work, we review the existing fast and memory-efficient PCA algorithms and implementations and evaluate their practical application to large-scale scRNA-seq datasets. Our benchmark shows that some PCA algorithms based on Krylov subspace and randomized singular value decomposition are fast, memory-efficient, and more accurate than the other algorithms. Conclusion We develop a guideline to select an appropriate PCA implementation based on the differences in the computational environment of users and developers.
Treating Hypertension in Chronic Obstructive Pulmonary Disease
Authors: Shannon W. Finks, Mark J. Rumbak, Timothy H. Self
Journal: New England Journal of Medicine (2020)

This review considers recent evidence concerning hypertension management in patients with chronic obstructive pulmonary disease, including the effects of antihypertensive-drug classes on exacerbations, hospitalizations, and adverse pulmonary outcomes.
Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial
Authors: P.G. Corrie, A. Marshall, P.D. Nathan, P. Lorigan, M. Gore, S. Tahir, G. Faust, C.G. Kelly, M. Marples, S.J. Danson, E. Marshall, S.J. Houston, R.E. Board, A.M. Waterston, J.P. Nobes, M. Harries, S. Kumar, A. Goodman, A. Dalgleish, A. Martin-Clavijo, S. Westwell, R. Casasola, D. Chao, A. Maraveyas, P.M. Patel, C.H. Ottensmeier, D. Farrugia, A. Humphreys, B. Eccles, G. Young, E.O. Barker, C. Harman, M. Weiss, K.A. Myers, A. Chhabra, S.H. Rodwell, J.A. Dunn, M.R. Middleton
Journal: Annals of Oncology (2019)

Ann Oncol 2018; 29(8): 1843–1852 (doi: 10.1093/annonc/mdy229) In the original article, there was an error in Figure 3. The figure has now been corrected as below in the online version of the article. Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trialAnnals of OncologyVol. 29Issue 8PreviewBevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Full-Text PDF Open Access
Late Relapse of Diabetes After Bariatric Surgery: Not Rare, but Not a Failure
Authors: Ali Aminian, Josep Vidal, Paulina Salminen, Christopher D. Still, Zubaidah Nor Hanipah, Gautam Sharma, Chao Tu, G. Craig Wood, Ainitze Ibarzabal, Amanda Jimenez, Stacy A. Brethauer, Philip R. Schauer, Kamal Mahawar
Journal: Diabetes Care (2020)

OBJECTIVE To characterize the status of cardiometabolic risk factors after late relapse of type 2 diabetes mellitus (T2DM) and to identify factors predicting relapse after initial diabetes remission following bariatric surgery to construct prediction models for clinical practice. RESEARCH DESIGN AND METHODS Outcomes of 736 patients with T2DM who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at an academic center (2004–2012) and had ≥5 years’ glycemic follow-up were assessed. Of 736 patients, 425 (58%) experienced diabetes remission (HbA1c &amp;lt;6.5% [48 mmol/mol] with patients off medications) in the 1st year after surgery. These 425 patients were followed for a median of 8 years (range 5–14) to characterize late relapse of diabetes. RESULTS In 136 (32%) patients who experienced late relapse, a statistically significant improvement in glycemic control, number of diabetes medications including insulin use, blood pressure, and lipid profile was still observed at long-term. Independent baseline predictors of late relapse were preoperative number of diabetes medications, duration of T2DM before surgery, and SG versus RYGB. Furthermore, patients who relapsed lost less weight during the 1st year after surgery and regained more weight afterward. Prediction models were constructed and externally validated. CONCLUSIONS While late relapse of T2DM is a real phenomenon (one-third of our cohort), it should not be considered a failure, as the trajectory of the disease and its related cardiometabolic risk factors is changed favorably after bariatric surgery. Earlier surgical intervention, RYGB (compared with SG) and more weight loss (less late weight regain) are associated with less diabetes relapse in the long-term.
Multivariate Analysis of Cytokines and Angiogenic Factors (CAFS) and Established Prognostic Parameters in Metastatic Renal Cell Carcinoma (MRCC) Patients (PTS) Receiving Pazopanib or Placebo
Authors: A. Zurita-Saavedra, Y. Liu, Y. Lin, H.T. Tran, L.N. Pandite, J.V. Heymach
Journal: Annals of Oncology (2012)
Syncope in a young woman
Authors: Krishna Kumar Mohanan Nair, Narayanan Namboodiri, Ajitkumar Valaparambil
Journal: BMJ (2020)

A previously well and active 25 year old woman with no underlying structural heart disease presented with recurrent episodes of new onset syncope over a period of six hours. Her pulse was irregularly irregular at a rate of 230 beats/min. She was hypotensive with a blood pressure of 80/60 mm Hg. Twelve lead surface electrocardiogram (ECG) taken on admission is shown in fig 1. She was immediately electrically cardioverted to sinus rhythm with 150 J. She reported no history of recreational drug use or family history of sudden cardiac death.



Fig 1 
Surface electrocardiogram during …
Which Is the Optimal Scan Time of 18F-DOPA PET/CT in Patients With Recurrent Medullary Thyroid Carcinoma?
Authors: Silvia Taralli, Margherita Lorusso, Amedeo Capotosti, Valerio Lanni, Luca Indovina, Vittoria Rufini
Journal: Clinical Nuclear Medicine (2019)

Purpose The aim of this retrospective study was to determine, by dynamic acquisition, the optimal scan time of 18 F-DOPA PET/CT in patients with recurrent medullary thyroid carcinoma (MTC). Methods Twenty-one patients with suspected recurrent MTC underwent dynamic 18 F-DOPA PET/CT (lasting 45 minutes) followed by whole-body scan. Three different time intervals of dynamic acquisition were evaluated: ultra-early phase (2–5 minutes), early phase (5–10 minutes), and late phase (40–45 minutes). The number and SUVmax of all detected lesions among the 3 dynamic acquisition phases were compared on qualitative and semiquantitative analyses. Time-activity curves, SUVmax washout rate between ultra-early or early phase and late phase, and signal-to-noise ratio (SNR) between lesion and background activity were also calculated. Results At dynamic acquisition, 15 of 21 patients were classified as PET-positive and 6 of 21 as PET-negative, with overall 21 detected lesions. Ultra-early and early imaging provided a better lesion visualization than late phase in more than 70% of cases, as also reflected by SNR (mean SNR reduction between 2 and 45 minutes, −45% ± 19%). Time-activity curves showed a rapid tracer accumulation in MTC lesions, with an average maximum uptake at 2 minutes after injection. Mean lesion SUVmax was 2-fold higher in ultra-early frames compared with last frames (mean washout rate, −44% ± 33%). Finally, compared with whole-body imaging in the same field of view, dynamic acquisition identified 1 additional positive patient and 3 additional lesions in 2 patients. Conclusions Our study, showing a very fast 18 F-DOPA uptake in MTC lesions, suggests the utility to obtain early PET/CT images, already at 2 to 5 minutes after tracer injection, when maximum lesion tracer uptake is reached.
Successful Intra-arterial Peptide Receptor Radionuclide Therapy of DOTATOC-Negative High-Grade Liver Metastases of a Pancreatic Neuroendocrine Neoplasm Using 177Lu-DOTA-LM3
Authors: Jingjing Zhang, Harshad R. Kulkarni, Aviral Singh, Richard P. Baum
Journal: Clinical Nuclear Medicine (2019)

Abstract Radiolabeled somatostatin receptor (SSTR) antagonists have shown promise for imaging neuroendocrine neoplasms and the superiority to SSTR agonists, with lower liver background especially for the sensitive detection of liver metastases, higher tumor-to-background ratio, and favorable pharmacokinetics. The clinical data of radiolabeled SSTR antagonists for therapy are still limited. We report our experience treating a young patient with DOTATOC-negative high-grade liver metastases of a pancreatic neuroendocrine neoplasm who underwent intra-arterial peptide receptor radionuclide therapy using SSTR antagonist 177 Lu-DOTA-LM3, demonstrating an excellent response, nearly complete remission according to molecular imaging criteria and morphological partial remission, without any significant toxicity.
Performance difference of graph-based and alignment-based hybrid error correction methods for error-prone long reads
Authors: Anqi Wang, Kin Fai Au
Journal: Genome biology (2020)

The error-prone third-generation sequencing (TGS) long reads can be corrected by the high-quality second-generation sequencing (SGS) short reads, which is referred to as hybrid error correction. We here investigate the influences of the principal algorithmic factors of two major types of hybrid error correction methods by mathematical modeling and analysis on both simulated and real data. Our study reveals the distribution of accuracy gain with respect to the original long read error rate. We also demonstrate that the original error rate of 19% is the limit for perfect correction, beyond which long reads are too error-prone to be corrected by these methods.
Implications of Abnormal Exercise Electrocardiography With Normal Stress Echocardiography
Authors: Melissa A. Daubert, Joseph Sivak, Allison Dunning, Pamela S. Douglas, Brian Coyne, Tracy Y. Wang, Daniel B. Mark, Eric J. Velazquez
Journal: JAMA Internal Medicine (2020)

<h3>Importance</h3> Patients with abnormal (positive) exercise electrocardiography, but normal stress echocardiography (+ECG/−Echo) are commonly encountered in clinical practice; however, the prognostic significance of this discordant result is unclear. <h3>Objective</h3> To determine whether patients with +ECG/−Echo have a higher rate of adverse clinical events and a poorer prognosis than patients with negative exercise ECG and normal stress Echo imaging (−ECG/−Echo). <h3>Design, Setting, and Participants</h3> Between January 1, 2000, and February 28, 2014, a total of 47 944 consecutive patients without known coronary artery disease who underwent exercise stress Echo at Duke University Medical Center were evaluated for inclusion in this observational cohort study. Data analysis was conducted from January 1, 2000, to December 31, 2016. <h3>Interventions/Exposures</h3> Patients were categorized as having −ECG/−Echo, +ECG/−Echo, or +Echo (−ECG/+Echo and +ECG/+Echo). <h3>Main Outcomes and Measures</h3> The primary outcome was a composite end point of death, myocardial infarction, hospitalization for unstable angina, and coronary revascularization. Secondary outcomes included individual adverse events and downstream testing. <h3>Results</h3> After excluding submaximal tests and nondiagnostic ECG or stress imaging results, 15 077 patients (mean [SD] age, 52 [13] years; 6228 [41.3%] men) were classified by stress test results. Of these, 12 893 patients (85.5%) had −ECG/−Echo, 1286 patients (8.5%) had +ECG/−Echo, and 898 patients (6.0%) had +Echo. Through a median follow-up of 7.3 (interquartile range, 4.4-10.0) years, the composite end point occurred in 794 patients with −ECG/−Echo (8.5%), 142 patients with +ECG/−Echo (14.6%), and 297 patients with +Echo (37.4%). Death occurred in 425 patients with −ECG/−Echo (4.8%), 50 patients with +ECG/−Echo (5.9%), and 70 patients with +Echo (11.2%). Myocardial infarction occurred in 195 patients with −ECG/−Echo (2.2%), 31 patients with +ECG/−Echo (3.6%), and 59 patients with +Echo (8.7%). The addition of stress ECG findings to clinical and exercise data yielded incremental prognostic value. Patients with −ECG/−Echo imaging results had the least downstream testing (2.3%), followed by +ECG/−Echo (12.8%), and +Echo (33.6%) (<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The presence of +ECG results with normal stress Echo imaging may identify a population of patients who are at slightly increased risk for adverse cardiac events, which was not previously recognized. Further study is needed to determine whether these patients will benefit from intensification of medical management.
Coronary Artery Target Selection and Survival After Bilateral Internal Thoracic Artery Grafting
Authors: Faisal G. Bakaeen, Kirthi Ravichandren, Eugene H. Blackstone, Penny L. Houghtaling, Edward G. Soltesz, Douglas R. Johnston, Stephanie L. Mick, José L. Navia, Michael Zhen-Yu Tong, Kenneth R. McCurry, Rami Akhrass, Mouin Abdallah, Gösta B. Pettersson, Nicholas M. Smedira, Eric E. Roselli, A. Marc Gillinov, Lars G. Svensson
Journal: Journal of the American College of Cardiology (2020)
Severe combined immunodeficiency caused by inositol-trisphosphate 3-kinase B (ITPKB) deficiency
Authors: Abduarahman Almutairi, Jacqueline G. Wallace, Faris Jaber, Mohammed F. Alosaimi, Jennifer Jones, Mohamed T.H. Sallam, M.H. Elnagdy, Janet Chou, Ali Sobh, Raif S. Geha
Journal: Journal of Allergy and Clinical Immunology (2020)
Bone Tissue Engineering via Carbon‐Based Nanomaterials
Authors: Zhili Peng, Tianshu Zhao, Yiqun Zhou, Shanghao Li, Jiaojiao Li, Roger M. Leblanc
Journal: Advanced Healthcare Materials (2020)

Bone tissue engineering (BTE) has received significant attention due to its enormous potential in treating critical-sized bone defects and related diseases. Traditional materials such as metals, ceramics, and polymers have been widely applied as BTE scaffolds; however, their clinical applications have been rather limited due to various considerations. Recently, carbon-based nanomaterials attract significant interests for their applications as BTE scaffolds due to their superior properties, including excellent mechanical strength, large surface area, tunable surface functionalities, high biocompatibility as well as abundant and inexpensive nature. In this article, recent studies and advancements on the use of carbon-based nanomaterials with different dimensions such as graphene and its derivatives, carbon nanotubes, and carbon dots, for BTE are reviewed. Current challenges of carbon-based nanomaterials for BTE and future trends in BTE scaffolds development are also highlighted and discussed.
Short-term exposure to ambient fine particulate matter and out-of-hospital cardiac arrest: a nationwide case-crossover study in Japan
Authors: Bing Zhao, Fay H Johnston, Farhad Salimi, Masahiko Kurabayashi, Kazuaki Negishi
Journal: The Lancet Planetary Health (2020)

PM2·5 is an important but modifiable environmental risk factor, not only for pulmonary diseases and cancers, but for cardiovascular health. However, the evidence regarding the association between air pollution and acute cardiac events, such as out-of-hospital cardiac arrest (OHCA), is inconsistent, especially at concentrations lower than the WHO daily guideline (25 μg/m3). This study aimed to determine the associations between exposure to ambient air pollution and the incidence of OHCA.In this nationwide case-crossover study, we linked prospectively collected population-based registry data for OHCA in Japan from Jan 1, 2014, to Dec 31, 2015, with daily PM2·5, carbon monoxide (CO), nitrogen dioxide (NO2), photochemical oxidants (Ox), and sulphur dioxide (SO2) exposure on the day of the arrest (lag 0) or 1-3 days before the arrest (lags 1-3), as well as the moving average across days 0-1 and days 0-3. Daily exposure was calculated by averaging the measurements from all PM2·5 monitoring stations in the same prefecture. The effect of PM2·5 on risk of all-cause or cardiac OHCA was estimated using a time-stratified case-crossover design coupled with conditional logistic regression analysis, adjusted for daily temperature and relative humidity. Single-pollutant models were also investigated for the individual gaseous pollutants (CO, NO2, Ox, and SO2), as well as two-pollutant models for PM2·5 with these gaseous pollutants. Subgroup analyses were done by sex and age.Over the 2 years, 249 372 OHCAs were identified, with 149 838 (60·1%) presumed of cardiac origin. The median daily PM2·5 was 11·98 μg/m3 (IQR 8·13-17·44). Each 10 μg/m3 increase in PM2·5 was associated with increased risk of all-cause OHCA on the same day (odds ratio [OR] 1·016, 95% CI 1·009-1·023) and at lags of up to 3 days, ranging from OR 1·015 (1·008-1·022) at lag 1 to 1·033 (1·023-1·043) at lag 0-3. Results for cardiac OHCA were similar (ORs ranging from 1·016 [1·007-1·025] at lags 1 and 2 to 1·034 [1·021-1·047] at lag 0-3). Patients older than 65 years were more susceptible to PM2·5 exposure than younger age groups but no sex differences were identified. CO, Ox, and SO2 were also positively associated with OHCA while NO2 was not. However, in two-pollutant models of PM2·5 and gaseous pollutants, only PM2·5 (positive association) and NO2 (negative association) were independently associated with increased risk of OHCA.Short-term exposure to PM2·5 was associated with an increased risk of OHCA even at relatively low concentrations. Regulatory standards and targets need to incorporate the potential health gains from continual air quality improvement even in locations already meeting WHO standards.None.
John Phillips Mckay
Authors: Simon Mckay, Hannah Mckay
Journal: BMJ (2020)

John Phillips Mckay was the loving husband of Marjorie of blessed memory, a much loved dad, uncle, grandad, friend, mentor, and inspiration. To many thousands of patients and their families he was either Dr John or Dr Mckay, depending on their preference.

John was born in Llandrindod Wells, Wales, owing to war time evacuation of his mother (a teacher). They returned to Liverpool after the war ended. He went on to attend Liverpool medical school graduating in 1966. He started his career at Birkenhead General Hospital, moved on to the forensic psychiatric unit at Rainhill Hospital, and ultimately settled in general practice, initially in Wallasey …
Long-term air pollution exposure is associated with increased severity of rhinitis in 2 European cohorts
Authors: Emilie Burte, Bénédicte Leynaert, Alessandro Marcon, Jean Bousquet, Meriem Benmerad, Roberto Bono, Anne-Elie Carsin, Kees de Hoogh, Bertil Forsberg, Frederic Gormand, Joachim Heinrich, Jocelyne Just, Mark Nieuwenhuijsen, Isabelle Pin, Morgane Stempfelet, Jordi Sunyer, Simona Villani, Nino Künzli, Valérie Siroux, Deborah Jarvis, Rachel Nadif, Bénédicte Jacquemin
Journal: Journal of Allergy and Clinical Immunology (2020)
Three-dimensional self-assembling nanofiber matrix rejuvenates aged/degenerative human tendon stem/progenitor cells
Authors: Heyong Yin, Franziska Strunz, Zexing Yan, Jiaju Lu, Christoph Brochhausen, Stefanie Kiderlen, Hauke Clausen-Schaumann, Xiumei Wang, Manuela E. Gomes, Volker Alt, Denitsa Docheva
Journal: Biomaterials (2020)

The poor healing capacity of tendons is known to worsen in the elderly. During tendon aging and degeneration, endogenous human tendon stem/progenitor cells (hTSPCs) experience profound pathological changes. Here, we explored a rejuvenation strategy for hTSPCs derived from aged/degenerated Achilles tendons (A-TSPCs) by providing three-dimensional (3D) nanofiber hydrogels and comparing them to young/healthy TSPCs (Y-TSPCs). RADA peptide hydrogel has a self-assembling ability, forms a nanofibrous 3D niche and can be further functionalized by adding RGD motifs. Cell survival, apoptosis, and proliferation assays demonstrated that RADA and RADA/RGD hydrogels support A-TSPCs in a comparable manner to Y-TSPCs. Moreover, they rejuvenated A-TSPCs to a phenotype similar to that of Y-TSPCs, as evidenced by restored cell morphology and cytoskeletal architecture. Transmission electron, confocal laser scanning and atomic force microscopies demonstrated comparable ultrastructure, surface roughness and elastic modulus of A- and Y-TSPC-loaded hydrogels. Lastly, quantitative PCR revealed similar expression profiles, as well a significant upregulation of genes related to tenogenesis and multipotency. Taken together, the RADA-based hydrogels exert a rejuvenating effect by recapitulating in vitro specific features of the natural microenvironment of human TSPCs, which strongly indicates their potential to direct cell behaviour and overcome the challenge of cell aging and degeneration in tendon repair.
Letter to the Editor: Regional Epidemics of Nonalcoholic Fatty Liver Disease: Timing of Westernization and Ethnicity Matter
Authors: Jee‐Fu Huang, Chia‐Yen Dai, Ming‐Lung Yu, Wan‐Long Chuang
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the article by Zhou et al.,(1) who studied the epidemiological characteristics of nonalcoholic fatty liver disease (NAFLD) in China. The study was ambitious, aiming to clarify the status of this common liver disorder in a large country. It provided a big piece of the puzzle across different variables, including time period, age, sex, body mass index, ethnicity, geographical region, and income. However, two points should be taken into consideration. The first is their results regarding the regional difference of NAFLD prevalence based on the meta‐analysis study design. The westernization of lifestyle largely contributes to the regional epidemics. However, the northwest region, comprising mostly Uygur and Hui populations, carries the highest prevalence of NAFLD. The epidemics echo a previous study showing that people in Central Asia and the Middle East possess a high susceptibility for NAFLD development.(2) The difference in prevalence could not be sufficiently explained by the timing of changing diet and lifestyle in the non‐Han regions. Therefore, the results could not be simply explained by the heavy and salty meat diet in the northwest region, which the authors mentioned in the Discussion section. The second is that NAFLD is a metabolic disorder attributed mainly to environmental and host factors. Genetic predisposition plays a major role in the development of NAFLD and its subsequent phenotypic outcomes. The Island of Taiwan, which has a high prevalence of NAFLD,(3) also has a highly heterogeneous population, made up of indigenous people (1.5%), Minnan (73.5%), Hakka (17.5%), and mainland Chinese (7.5%) who arrived from the mainland after World War II. Minnan and Hakka are also ethnic groups who immigrated to Taiwan from the southeast coast of mainland China beginning in the 17th century. Genetically, even Minnan and Hakka showed affinities to Southern Asian populations, as determined by phylogenetic trees and correspondence analysis calculated from human leukocyte antigen allele frequencies.(4) We suggest that this genetic heterogeneity should be taken into account in epidemiologic analyses of this kind.