tbuckley/cabot-search huggingface dataset:
Not Only Diabetes but Also Prediabetes Leads to Functional Decline and Disability in Older Adults
Authors: Ying Shang, Laura Fratiglioni, Davide Liborio Vetrano, Abigail Dove, Anna-Karin Welmer, Weili Xu
Journal: Diabetes Care (2021)

OBJECTIVE Diabetes is linked to functional decline, but the impact of prediabetes on physical function is unknown. We aimed to examine and compare the impact of prediabetes and diabetes on physical function and disability progression and to explore whether cardiovascular diseases (CVDs) mediate these associations. RESEARCH DESIGN AND METHODS A cohort of 2,013 participants aged ≥60 from the Swedish National Study on Aging and Care in Kungsholmen, an ongoing population-based longitudinal study, was monitored for up to 12 years. Physical function was measured with chair stand (s) and walking speed (m/s) tests, and disability was measured by summing the numbers of impaired basic and instrumental activities of daily living. Diabetes was identified through medical examinations or clinical records, medication use, or glycated hemoglobin (HbA1c) ≥6.5%. Prediabetes was defined as HbA1c ≥5.7–6.4% in participants free of diabetes. CVDs were ascertained through clinical examinations and the National Patient Register. Data were analyzed using mixed-effect models and mediation models. RESULTS At baseline, 650 (32.3%) had prediabetes and 151 had diabetes (7.5%). In multiadjusted mixed-effect models, prediabetes was associated with an increased chair stand time (β 0.33, 95% CI 0.05–0.61), a decreased walking speed (β −0.006, 95% CI −0.010 to −0.002), and an accelerated disability progression (β 0.05, 95% CI 0.01–0.08), even after controlling for the future development of diabetes. Diabetes led to faster functional decline than prediabetes. In mediation analyses, CVDs mediated 7.1%, 7.8%, and 20.9% of the associations between prediabetes and chair stand, walking speed, and disability progression, respectively. CONCLUSIONS Prediabetes, in addition to diabetes, is associated with faster functional decline and disability, independent of the future development of diabetes. This association may be in part mediated by CVDs.
Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
Authors: Mary B. Daly, Tuya Pal, Michael P. Berry, Saundra S. Buys, Patricia Dickson, Susan M. Domchek, Ahmed Elkhanany, Susan Friedman, Michael Goggins, Mollie L. Hutton, Beth Y. Karlan, Seema Khan, Catherine Klein, Wendy Kohlmann, Allison W. Kurian, Christine Laronga, Jennifer K. Litton, Julie S. Mak, Carolyn S. Menendez, Sofia D. Merajver, Barbara S. Norquist, Kenneth Offit, Holly J. Pederson, Gwen Reiser, Leigha Senter-Jamieson, Kristen Mahoney Shannon, Rebecca Shatsky, Kala Visvanathan, Jeffrey N. Weitzel, Myra J. Wick, Kari B. Wisinski, Matthew B. Yurgelun, Susan D. Darlow, Mary A. Dwyer
Journal: Journal of the National Comprehensive Cancer Network (2021)

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.
A comparison of two hybrid closed-loop systems in adolescents and young adults with type 1 diabetes (FLAIR): a multicentre, randomised, crossover trial
Authors: Richard M Bergenstal, Revital Nimri, Roy W Beck, Amy Criego, Lori Laffel, Desmond Schatz, Tadej Battelino, Thomas Danne, Stuart A Weinzimer, Judy Sibayan, Mary L Johnson, Ryan J Bailey, Peter Calhoun, Anders Carlson, Elvira Isganaitis, Rachel Bello, Anastasia Albanese-O'Neill, Klemen Dovc, Torben Biester, Kate Weyman, Korey Hood, Moshe Phillip
Journal: The Lancet (2021)
EGFR-targeted multifunctional nanoparticles induce autophagic cell death and enhance the antitumor effect of cisplatin and γ-irradiation in non-small cell lung cancer cells
Authors: Tomohisa Yokoyama, Justina Tam, Tim Larson, Ailing Scott, Seiji Kondo, Jack Roth, Konstantin Sokolov, Rajagopal Ramesh
Journal: Cancer Research (2008)

5606  The Epidermal growth factor receptor (EGFR) is overexpressed in approximately 80% of non-small cell lung cancers (NSCLC) and is a target for novel therapeutics. We have developed a tumor-targeted multifunctional nanoparticle which consists of a paramagnetic iron core that is surrounded by a gold layer and is functionalized with a monoclonal anti-EGFR antibody. The iron core is used for magnetic resonance imaging (MRI), the gold is used for optical imaging and the antibody for therapy. In the present study, we investigated the in vitro effects of these EGFR-targeted multifunctional nanoparticles on NSCLC cell lines (HCC827, H1299, H1819), lung fibroblasts (MRC-9, WI38), and normal human bronchial epithelial cells (NHBE). The levels of EGFR were higher in all the NSCLC cell lines than in normal cells, indicating that NSCLC cells could be selectively killed by targeting the EGFR-mediated signal transduction. Treatment with the EGFR-targeted nanoparticles (1X109 particles) for 72 hours significantly inhibited the growth of all three tumor cell lines but not the fibroblasts or NHBE cells. The growth inhibitory effect was dose and time dependent. Spectroscopic analysis and optical images taken over a 24 h period after treatment of cells with the nanoparticles showed that the concentration of nanoparticles bound to NSCLC cells increased in a time dependent manner. Molecular analysis of nanoparticle-treated tumor cells revealed reduced levels of activated (phosphorylated) EGFR, AKT, p38MAPK, and p44/42MAPK. Furthermore, induction of autophagy followed by apoptosis was observed in nanoparticle-treated tumor cells. In vitro phantom studies using MRI and the iron-containing nanoparticles as contrast agent revealed the spatial distribution of tumor cells. Antibody blocking studies using EGFR-positive (A431) and -negative (MDA-MB-435) tumor cells revealed nanoparticles specificity for EGFR. Since EGFR-targeted therapies have proven more effective when used in combination therapy, we investigated the therapeutic effects of the EGFR-targeted nanoparticles in combination with cisplatin (CDDP) and γ-irradiation (IR). Treatment of tumor cells with the nanoparticles plus low doses of CDDP (0.01 to 0.25 uM) or IR (1 Gy) resulted in an additive increase in inhibitory effects compared to the inhibitory effect produced by individual treatments. Our findings demonstrate EGFR-targeted multifunctional nanoparticles selectively induce cell death in NSCLC cells but not in normal cells, and the therapeutic effect is enhanced when the nanoparticles are combined with CDDP or IR.
Agnes (“Nan”) Blair
Authors: Judith Blair, Jane Preston
Journal: BMJ (2021)

Agnes Blair (“Nan”) qualified from Glasgow University, while also managing to achieve international caps for the Scotland Ladies Golf Team. Nan also met her husband to be, Donald, the love of her life, on the first tee at Royal Troon Golf Course. She was a true family doctor, working in Bridge of Weir from 1962 to 1991. She looked after …
Cauda equina syndrome
Authors: Kevin Barraclough
Journal: BMJ (2021)

### What you need to know

A 42 year old woman presented to an out-of-hours general practitioner with a five day history of low back pain with burning pain radiating into her right foot. She had a body mass index of 39 and a 12 year history of chronic low back pain with intermittent left sided “sciatica” pain in her thigh. She had noted “tingling” in her genital area. There was no incontinence. The general practitioner considered, on examination, that anal tone and perianal sensation were normal, as were power, tone, reflexes, and sensation in the legs. The patient was treated with analgesia and given advice to seek review if she developed bilateral sciatica, became incontinent, or developed leg weakness. Three days later, she was admitted with cauda equina syndrome and underwent surgical decompression. She was left with lower limb weakness, numbness of the genitalia, loss of sexual function, and urinary and faecal incontinence. 

Cauda equina syndrome (CES) is a rare condition in which the …
Large-scale tumor-associated collagen signatures identify high-risk breast cancer patients
Authors: Gangqin Xi, Wenhui Guo, Deyong Kang, Jianli Ma, Fangmeng Fu, Lida Qiu, Liqin Zheng, Jiajia He, Na Fang, Jianhua Chen, Jingtong Li, Shuangmu Zhuo, Xiaoxia Liao, Haohua Tu, Lianhuang Li, Qingyuan Zhang, Chuan Wang, Stephen A Boppart, Jianxin Chen
Journal: Theranostics (2021)

The notion of personalized medicine demands proper prognostic biomarkers to guide the optimal therapy for an invasive breast cancer patient. However, various risk prediction models based on conventional clinicopathological factors and emergent molecular assays have been frequently limited by either a low strength of prognosis or restricted applicability to specific types of patients. Therefore, there is a critical need to develop a strong and general prognosticator.
Ratatosk: hybrid error correction of long reads enables accurate variant calling and assembly
Authors: Guillaume Holley, Doruk Beyter, Helga Ingimundardottir, Peter L. Møller, Snædis Kristmundsdottir, Hannes P. Eggertsson, Bjarni V. Halldorsson
Journal: Genome biology (2021)

A major challenge to long read sequencing data is their high error rate of up to 15%. We present Ratatosk, a method to correct long reads with short read data. We demonstrate on 5 human genome trios that Ratatosk reduces the error rate of long reads 6-fold on average with a median error rate as low as 0.22 %. SNP calls in Ratatosk corrected reads are nearly 99 % accurate and indel calls accuracy is increased by up to 37 %. An assembly of Ratatosk corrected reads from an Ashkenazi individual yields a contig N50 of 45 Mbp and less misassemblies than a PacBio HiFi reads assembly.
Changes in Albuminuria Predict Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the LEADER Trial
Authors: Frederik Persson, Stephen C. Bain, Ofri Mosenzon, Hiddo J.L. Heerspink, Johannes F.E. Mann, Richard Pratley, Itamar Raz, Thomas Idorn, Søren Rasmussen, Bernt Johan von Scholten, Peter Rossing
Journal: Diabetes Care (2021)

OBJECTIVE A post hoc analysis to investigate the association between 1-year changes in albuminuria and subsequent risk of cardiovascular and renal events. RESEARCH DESIGN AND METHODS LEADER was a randomized trial of liraglutide up to 1.8 mg/day versus placebo added to standard care for 3.5–5 years in 9,340 participants with type 2 diabetes and high cardiovascular risk. We calculated change in urinary albumin-to-creatinine ratio (UACR) from baseline to 1 year in participants with &amp;gt;30% reduction (n = 2,928), 30–0% reduction (n = 1,218), or any increase in UACR (n = 4,124), irrespective of treatment. Using Cox regression, risks of major adverse cardiovascular events (MACE) and a composite nephropathy outcome (from 1 year to end of trial in subgroups by baseline UACR [&amp;lt;30 mg/g, 30–300 mg/g, or ≥300 mg/g]) were assessed. The analysis was adjusted for treatment allocation alone as a fixed factor and for baseline variables associated with cardiovascular and renal outcomes. RESULTS For MACE, hazard ratios (HRs) for those with &amp;gt;30% and 30–0% UACR reduction were 0.82 (95% CI 0.71, 0.94; P = 0.006) and 0.99 (0.82, 1.19; P = 0.912), respectively, compared with any increase in UACR (reference). For the composite nephropathy outcome, respective HRs were 0.67 (0.49, 0.93; P = 0.02) and 0.97 (0.66, 1.43; P = 0.881). Results were independent of baseline UACR and consistent in both treatment groups. After adjustment, HRs were significant and consistent in &amp;gt;30% reduction subgroups with baseline micro- or macroalbuminuria. CONCLUSIONS A reduction in albuminuria during the 1st year was associated with fewer cardiovascular and renal outcomes, independent of treatment. Albuminuria monitoring remains an important part of diabetes care, with great unused potential.
Ultrasound assessment of pulmonary fibroproliferative changes in severe COVID-19: a quantitative correlation study with histopathological findings
Authors: Renata Aparecida de Almeida Monteiro, Amaro Nunes Duarte-Neto, Luiz Fernando Ferraz da Silva, Ellen Pierre de Oliveira, Ellen Caroline Toledo do Nascimento, Thais Mauad, Paulo Hilário do Nascimento Saldiva, Marisa Dolhnikoff
Journal: Intensive Care Medicine (2021)
The SIRPα–CD47 immune checkpoint in NK cells
Authors: Tobias Deuse, Xiaomeng Hu, Sean Agbor-Enoh, Moon K. Jang, Malik Alawi, Ceren Saygi, Alessia Gravina, Grigol Tediashvili, Vinh Q. Nguyen, Yuan Liu, Hannah Valantine, Lewis L. Lanier, Sonja Schrepfer
Journal: The Journal of Experimental Medicine (2021)

Here we report on the existence and functionality of the immune checkpoint signal regulatory protein α (SIRPα) in NK cells and describe how it can be modulated for cell therapy. NK cell SIRPα is up-regulated upon IL-2 stimulation, interacts with target cell CD47 in a threshold-dependent manner, and counters other stimulatory signals, including IL-2, CD16, or NKG2D. Elevated expression of CD47 protected K562 tumor cells and mouse and human MHC class I–deficient target cells against SIRPα+ primary NK cells, but not against SIRPα− NKL or NK92 cells. SIRPα deficiency or antibody blockade increased the killing capacity of NK cells. Overexpression of rhesus monkey CD47 in human MHC-deficient cells prevented cytotoxicity by rhesus NK cells in a xenogeneic setting. The SIRPα–CD47 axis was found to be highly species specific. Together, the results demonstrate that disruption of the SIRPα–CD47 immune checkpoint may augment NK cell antitumor responses and that elevated expression of CD47 may prevent NK cell–mediated killing of allogeneic and xenogeneic tissues.
Advance Care Planning and the Cost of Pragmatism
Authors: Vinay Guduguntla, Tracy Wang, Deborah Grady
Journal: JAMA Internal Medicine (2021)

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 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 Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Unsupervised phenotypic clustering for determining clinical status in children with cystic fibrosis
Authors: Nicole Filipow, Gwyneth Davies, Eleanor Main, Neil J. Sebire, Colin Wallis, Felix Ratjen, Sanja Stanojevic
Journal: European Respiratory Journal (2021)

Background Cystic fibrosis (CF) is a multisystem disease in which the assessment of disease severity based on lung function alone may not be appropriate. The aim of the study was to develop a comprehensive machine-learning algorithm to assess clinical status independent of lung function in children. Methods A comprehensive prospectively collected clinical database (Toronto, Canada) was used to apply unsupervised cluster analysis. The defined clusters were then compared by current and future lung function, risk of future hospitalisation, and risk of future pulmonary exacerbation treated with oral antibiotics. A k-nearest-neighbours (KNN) algorithm was used to prospectively assign clusters. The methods were validated in a paediatric clinical CF dataset from Great Ormond Street Hospital (GOSH). Results The optimal cluster model identified four (A–D) phenotypic clusters based on 12 200 encounters from 530 individuals. Two clusters (A and B) consistent with mild disease were identified with high forced expiratory volume in 1 s (FEV 1 ), and low risk of both hospitalisation and pulmonary exacerbation treated with oral antibiotics. Two clusters (C and D) consistent with severe disease were also identified with low FEV 1 . Cluster D had the shortest time to both hospitalisation and pulmonary exacerbation treated with oral antibiotics. The outcomes were consistent in 3124 encounters from 171 children at GOSH. The KNN cluster allocation error rate was low, at 2.5% (Toronto) and 3.5% (GOSH). Conclusion Machine learning derived phenotypic clusters can predict disease severity independent of lung function and could be used in conjunction with functional measures to predict future disease trajectories in CF patients.
Efficacy and safety of dapagliflozin were similar in patients with type 2 DM and atherosclerotic CVD, regardless of PAD
Authors: Qiukui Hao, Gordon Guyatt
Journal: Annals of Internal Medicine (2021)

Source Citation Bonaca MP, Wiviott SD, Zelniker TA, et al. Dapagliflozin and cardiac, kidney, and limb outcomes in patients with and without peripheral artery disease in DECLARE-TIMI 58. Circulation. 2020;142:734-47. 32795086
Surgical ergonomics for urologists: a practical guide
Authors: Andrew T. Gabrielson, Marisa M. Clifton, Christian P. Pavlovich, Michael J. Biles, Mitchell Huang, Jacqueline Agnew, Phillip M. Pierorazio, Brian R. Matlaga, Petar Bajic, Zeyad R. Schwen
Journal: Nature Reviews Urology (2021)
Resequencing of global Tartary buckwheat accessions reveals multiple domestication events and key loci associated with agronomic traits
Authors: Kaixuan Zhang, Ming He, Yu Fan, Hui Zhao, Bin Gao, Keli Yang, Faliang Li, Yu Tang, Qiang Gao, Tao Lin, Muriel Quinet, Dagmar Janovská, Vladimir Meglič, Jacek Kwiatkowski, Olga Romanova, Nikhil Chrungoo, Tatsuro Suzuki, Zlata Luthar, Mateja Germ, Sun-Hee Woo, Milen I. Georgiev, Meiliang Zhou
Journal: Genome biology (2021)

Tartary buckwheat (Fagopyrum tataricum) is a nutritionally balanced and flavonoid-rich crop plant that has been in cultivation for 4000 years and is now grown globally. Despite its nutraceutical and agricultural value, the characterization of its genetics and its domestication history is limited.
Diffusion-weighted Imaging Allows for Downgrading MR BI-RADS 4 Lesions in Contrast-enhanced MRI of the Breast to Avoid Unnecessary Biopsy
Authors: Paola Clauser, Barbara Krug, Hubert Bickel, Matthias Dietzel, Katja Pinker, Victor-Frederic Neuhaus, Maria Adele Marino, Marco Moschetta, Nicoletta Troiano, Thomas H. Helbich, Pascal A.T. Baltzer
Journal: Clinical Cancer Research (2021)

Diffusion-weighted imaging with the calculation of an apparent diffusion coefficient (ADC) has been proposed as a quantitative biomarker on contrast-enhanced MRI (CE-MRI) of the breast. There is a need to approve a generalizable ADC cutoff. The purpose of this study was to evaluate whether a predefined ADC cutoff allows downgrading of BI-RADS 4 lesions on CE-MRI, avoiding unnecessary biopsies.This was a retrospective, multicentric, cross-sectional study. Data from five centers were pooled on the individual lesion level. Eligible patients had a BI-RADS 4 rating on CE-MRI. For each center, two breast radiologists evaluated the images. Data on lesion morphology (mass, non-mass), size, and ADC were collected. Histology was the standard of reference. A previously suggested ADC cutoff (≥1.5 × 10-3 mm2/second) was applied. A negative likelihood ratio of 0.1 or lower was considered as a rule-out criterion for breast cancer. Diagnostic performance indices were calculated by ROC analysis.There were 657 female patients (mean age, 42; SD, 14.1) with 696 BI-RADS 4 lesions included. Disease prevalence was 59.5% (414/696). The area under the ROC curve was 0.784. Applying the investigated ADC cutoff, sensitivity was 96.6% (400/414). The potential reduction of unnecessary biopsies was 32.6% (92/282).An ADC cutoff of ≥1.5 × 10-3 mm2/second allows downgrading of lesions classified as BI-RADS 4 on breast CE-MRI. One-third of unnecessary biopsies could thus be avoided.
Dermatologic care of incarcerated patients: A single-center descriptive study of teledermatology and face-to-face encounters
Authors: Joshua J. Clark, Ashley M. Snyder, Shreya A. Sreekantaswamy, Marta J. Petersen, Bethany K.H. Lewis, Aaron M. Secrest, Scott R. Florell
Journal: Journal of the American Academy of Dermatology (2021)
Cancer Statistics, 2021
Authors: Rebecca L. Siegel, Kimberly D. Miller, Hannah E. Fuchs, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2021)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
Abstract 14812: Hospital Readmission in Perioperative Stroke Patients After Invasive Cardiac Procedures: California State Inpatient Database Study
Authors: Nada Alrifai, Laith Alhuneafat, Khaled Al-Robaidi, Parthasarathy Thirumala
Journal: Circulation (2019)

Objective: Readmission rates are considered an important metric for evaluating health care quality. Stroke is a major complication following cardiac surgery. Our study aimed to evaluate the frequen...