tbuckley/cabot-search huggingface dataset:
Predictably unequal: understanding and addressing concerns that algorithmic clinical prediction may increase health disparities
Authors: Jessica K. Paulus, David M. Kent
Journal: npj Digital Medicine (2020)

The machine learning community has become alert to the ways that predictive algorithms can inadvertently introduce unfairness in decision-making. Herein, we discuss how concepts of algorithmic fairness might apply in healthcare, where predictive algorithms are being increasingly used to support decision-making. Central to our discussion is the distinction between algorithmic fairness and algorithmic bias. Fairness concerns apply specifically when algorithms are used to support polar decisions (i.e., where one pole of prediction leads to decisions that are generally more desired than the other), such as when predictions are used to allocate scarce health care resources to a group of patients that could all benefit. We review different fairness criteria and demonstrate their mutual incompatibility. Even when models are used to balance benefits-harms to make optimal decisions for individuals (i.e., for non-polar decisions)-and fairness concerns are not germane-model, data or sampling issues can lead to biased predictions that support decisions that are differentially harmful/beneficial across groups. We review these potential sources of bias, and also discuss ways to diagnose and remedy algorithmic bias. We note that remedies for algorithmic fairness may be more problematic, since we lack agreed upon definitions of fairness. Finally, we propose a provisional framework for the evaluation of clinical prediction models offered for further elaboration and refinement. Given the proliferation of prediction models used to guide clinical decisions, developing consensus for how these concerns can be addressed should be prioritized.
EPAS1 and VEGFA gene variants are related to the symptoms of acute mountain sickness in Chinese Han population: a cross-sectional study
Authors: Ji-Hang Zhang, Yang Shen, Chuan Liu, Jie Yang, Yuan-Qi Yang, Chen Zhang, Shi-Zhu Bian, Jie Yu, Xu-Bin Gao, Lai-Ping Zhang, Jing-Bin Ke, Fang-Zheng-Yuan Yuan, Wen-Xu Pan, Zhi-Nian Guo, Lan Huang
Journal: Military Medical Research (2020)

Abstract Background More people ascend to high altitude (HA) for various activities, and some individuals are susceptible to HA illness after rapidly ascending from plains. Acute mountain sickness (AMS) is a general complaint that affects activities of daily living at HA. Although genomic association analyses suggest that single nucleotide polymorphisms (SNPs) are involved in the genesis of AMS, no major gene variants associated with AMS-related symptoms have been identified. Methods In this cross-sectional study, 604 young, healthy Chinese Han men were recruited in June and July of 2012 in Chengdu, and rapidly taken to above 3700 m by plane. Basic demographic parameters were collected at sea level, and heart rate, pulse oxygen saturation (SpO 2 ), systolic and diastolic blood pressure and AMS-related symptoms were determined within 18–24 h after arriving in Lhasa. AMS patients were identified according to the latest Lake Louise scoring system (LLSS). Potential associations between variant genotypes and AMS/AMS-related symptoms were identified by logistic regression after adjusting for potential confounders (age, body mass index and smoking status). Results In total, 320 subjects (53.0%) were diagnosed with AMS, with no cases of high-altitude pulmonary edema or high-altitude cerebral edema. SpO 2 was significantly lower in the AMS group than that in the non-AMS group ( P = 0.003). Four SNPs in hypoxia-inducible factor-related genes were found to be associated with AMS before multiple hypothesis testing correction. The rs6756667 ( EPAS1 ) was associated with mild gastrointestinal symptoms ( P = 0.013), while rs3025039 ( VEGFA ) was related to mild headache ( P = 0.0007). The combination of rs6756667 GG and rs3025039 CT/TT further increased the risk of developing AMS ( OR = 2.70, P &lt; 0.001). Conclusions Under the latest LLSS, we find that EPAS1 and VEGFA gene variants are related to AMS susceptibility through different AMS-related symptoms in the Chinese Han population; this tool might be useful for screening susceptible populations and predicting clinical symptoms leading to AMS before an individual reaches HA. Trial registration Chinese Clinical Trial Registration, ChiCTR-RCS-12002232 . Registered 31 May 2012.
Can medical imaging identify the histopathological growth patterns of liver metastases?
Authors: Emily Latacz, Pieter-Jan van Dam, Christian Vanhove, Laura Llado, Benedicte Descamps, Núria Ruiz, Ines Joye, Dirk Grünhagen, Steven Van Laere, Piet Dirix, David G. Mollevi, Cornelis Verhoef, Luc Dirix, Peter Vermeulen
Journal: Seminars in Cancer Biology (2020)
Abstract 386: Prehospital Capnography in Non-Intubated Traumatic Brain Injury Patients: Association Between End-Tidal CO2 and Level of Consciousness
Authors: Bruce J Barnhart, Daniel W Spaite, Eric Helfenbein, Dawn Jorgenson, Saeed Babaeizadeh, Joshua B Gaither, Amber D Rice, Samuel M Keim, Chengcheng Hu
Journal: Circulation (2019)

Background: The EMS traumatic brain injury (TBI) guidelines encourage limiting prehospital intubation (ETI) to patients with profoundly depressed level of consciousness (LOC) and who cannot protect their airway or adequately ventilate without ETI. Thus, EMS providers may manage many TBI patients without intubating even when they have significant alterations in LOC. Monitoring End-Tidal CO2 by placing sensors in the nares (NC-CO2) of non-intubated patients may give providers valuable information about ventilatory status and trends. Study Objective: To evaluate the association between LOC and NC-CO2 in non-intubated TBI patients. Methods: Non-intubated cases from 6 EMS agencies reporting continuous monitor data (Philips MRx™) in the EPIC Study (NIH 1R01NS071049) were evaluated (4/13-3/17). Glasgow Coma Scale (GCS) was available from the EMS record in call cases. Comparisons in patient-level mean, median, lowest and highest NC-CO2 levels were made across GCS categories using clinically meaningful thresholds: &lt;15, &lt;12, &lt;9, and 3. Statistics: Wilcoxon rank-sum test. Results: Included were 106 cases [median age: 47 (range: 9-91), 66% male]. The Table shows the NC-CO2 patterns and comparisons across the GCS categories. In no case was there a significant difference in NC-CO2 between the better vs. worse mental status cohort. Conclusion: We believe this is the first evaluation of the association between NC-CO2 and mental status in TBI. Patients that had significant (and even profound) decreases in LOC, but whom paramedics chose not to intubate, had remarkably similar NC-CO2 patterns compared to those with normal or near-normal mental status. This may support the overall approach of limiting ETI to those with airway/ventilatory compromise or impending hypoxia as there was no evidence of increasing NC-CO2, indicative of hypercapnia, in the non-intubated patients even when they had very depressed LOC.
Global prevalence of Barrett’s oesophagus and oesophageal cancer in individuals with gastro-oesophageal reflux: a systematic review and meta-analysis
Authors: Leonardo Henry Eusebi, Giovanna Grazia Cirota, Rocco Maurizio Zagari, Alexander Charles Ford
Journal: Gut (2020)

Objectives Chronic gastro-oesophageal reflux might lead to the development of Barrett’s oesophagus (BO) or even oesophageal adenocarcinoma. There has been no definitive systematic review and meta-analysis of data to estimate global prevalence of BO or oesophageal adenocarcinoma in individuals with gastro-oesophageal reflux. Design We searched MEDLINE, Embase and Embase Classic to identify cross-sectional surveys that reported prevalence of BO or oesophageal adenocarcinoma in adults with gastro-oesophageal reflux. We extracted prevalence for all studies, both for endoscopically suspected and histologically confirmed cases. We calculated pooled prevalence according to study location, symptom frequency and sex, as well as ORs with 95% CIs. Results Of the 4963 citations evaluated, 44 reported prevalence of endoscopically suspected and/or histologically confirmed BO. Prevalence of BO among individuals with gastro-oesophageal reflux varied according to different geographical regions ranging from 3% to 14% for histologically confirmed BO with a pooled prevalence of 7.2% (95% CI 5.4% to 9.3%), whereas pooled prevalence for endoscopically suspected BO was 12.0% (95% CI 5.5% to 20.3%). There was heterogeneity in many of our analyses. Prevalence of BO was significantly higher in men, both for endoscopically suspected (OR=2.1; 95% CI 1.6 to 2.8) and histologically confirmed BO (OR=2.3; 95% CI 1.7 to 3.2). Dysplasia was present in 13.9% (95% CI 8.9% to 19.8%) of cases of histologically confirmed BO, 80.7% of which was low-grade. Conclusion The prevalence of Barrett’s oesophagus among individuals with gastro-oesophageal reflux varied strikingly among countries, broadly resembling the geographical distribution of gastro-oesophageal reflux itself. Prevalence of BO was significantly higher in men.
Cross-talk between GLI transcription factors and FOXC1 promotes T-cell acute lymphoblastic leukemia dissemination
Authors: Valeria Tosello, Deborah Bongiovanni, Jingjing Liu, Qingfei Pan, Koon-kiu Yan, Valentina Saccomani, Maaike Van Trimpont, Marco Pizzi, Martina Mazzoni, Angelo Paolo Dei Tos, Alberto Amadori, Paola Zanovello, Pieter Van Vlierberghe, Jiyang Yu, Erich Piovan
Journal: Leukemia (2020)
Changes in the amount of nutrient of packaged foods and beverages after the initial implementation of the Chilean Law of Food Labelling and Advertising: A nonexperimental prospective study
Authors: Marcela Reyes, Lindsey Smith Taillie, Barry Popkin, Rebecca Kanter, Stefanie Vandevijvere, Camila Corvalán
Journal: PLoS Medicine (2020)

Background In June 2016, the first phase of the Chilean Food Labelling and Advertising Law that mandated front-of-package warning labels and marketing restrictions for unhealthy foods and beverages was implemented. We assess foods and beverages reformulation after this initial implementation. Methods and findings A data set with the 2015 to 2017 nutritional information was developed collecting the information at 2 time periods: preimplementation (T0: January–February 2015 or 2016; n = 4,055) and postimplementation (T1: January–February 2017; n = 3,025). Quartiles of energy and nutrients of concern (total sugars, saturated fats, and sodium, per 100 g/100 mL) and the proportion of products with energy and nutrients exceeding the cutoffs of the law (i.e., products "high in") were compared pre- and postimplementation of the law in cross-sectional samples of products with sales >1% of their specific food or beverage groups, according to the Euromonitor International Database; a longitudinal subsample (i.e., products collected in both the pre- and postimplementation periods, n = 1,915) was also analyzed. Chi-squared, McNemar tests, and quantile regressions (simple and multilevel) were used for comparing T0 and T1. Cross-sectional analysis showed a significant decrease (T0 versus T1) in the proportion of product with any "high in" (from 51% [95% confidence interval (CI) 49–52] to 44% [95% CI 42–45]), mostly in food and beverage groups in which regulatory cutoffs were below the 75th percentile of the nutrient or energy distribution. Most frequent reductions were in the proportion of "high in" sugars products (in beverages, milks and milk-based drinks, breakfast cereals, sweet baked products, and sweet and savory spreads; from 80% [95% CI 73–86] to 60% [95% CI 51–69]) and in "high in sodium" products (in savory spreads, cheeses, ready-to-eat meals, soups, and sausages; from 74% [95% CI 69–78] to 27% [95% CI 20–35]). Conversely, the proportion of products "high in" saturated fats only decreased in savory spreads (p < 0.01), and the proportion of "high in" energy products significantly decreased among breakfast cereals and savory spreads (both p < 0.01). Quantile analyses showed that most of the changes took place close to the cutoff values, with only few exceptions of overall left shifts in distribution. Longitudinal analyses showed similar results. However, it is important to note that the nonexperimental nature of this study does not allow to imply causality of these findings. Conclusions Our results show that, after initial implementation of the Chilean Law of Food Labelling and Advertising, there was a significant decrease in the amount of sugars and sodium in several groups of packaged foods and beverages. Further studies should clarify how food reformulation will impact dietary quality of the population.
MSC-derived exosomes protect against oxidative stress-induced skin injury via adaptive regulation of the NRF2 defense system
Authors: Tian Wang, Zhe Jian, Andrius Baskys, Junle Yang, Jianying Li, Hua Guo, Yue Hei, Panpan Xian, Zhongzheng He, Zhengyu Li, Namiao Li, Qianfa Long
Journal: Biomaterials (2020)
Sensing Protein Quality in Cardiac Myocytes p62 Triggers a Lysosomal Response
Authors: Abhinav Diwan, Roberta A. Gottlieb
Journal: Circulation Research (2020)

onitoring protein quality and responding rapidly to accumulation of damaged proteins is critical for homoeostasis in long-lived cardiac myocytes that must function uninterrupted for the life of the organism.Indeed, accumulation of misfolded/damaged proteins triggers the unfolded protein response, which orchestrates key proteostatic systems to put brakes on protein synthesis and upregulates chaperones to facilitate protein folding.Simultaneously, the ubiquitin-proteasome and autophagy pathways are stimulated to remove unsalvageable proteins.Key signaling effectors are likely positioned to orchestrate the functioning of these systems and provide alternative pathways, lest one or more of these go awry.
Predicting lung nodules malignancy
Authors: M. Jacob, J. Romano, D. Ara..jo, J.M. Pereira, I. Ramos, V. Hespanhol
Journal: Pulmonology (2020)

It is critical to developing an accurate method for differentiating between malignant and benign solitary pulmonary nodules. This study aimed was to establish a predicting model of lung nodules malignancy in a real-world setting.The authors retrospectively analysed the clinical and computed tomography (CT) data of 121 patients with lung nodules, submitted to percutaneous CT-guided transthoracic biopsy, between 2014 and 2015. Multiple logistic regression was used to screen independent predictors for malignancy and to establish a clinical prediction model to evaluate the probability of malignancy.From a total of 121 patients, 75 (62%) were men and with a mean age of 64.7 years old. Multivariate logistic regression analysis identified six independent predictors of malignancy: age, gender, smoking status, current extra-pulmonary cancer, air bronchogram and nodule size (p<0.05). The area under the curve (AUC) was 0.8573.The prediction model established in this study can be used to assess the probability of malignancy in the Portuguese population, thereby providing help for the diagnosis of lung nodules and the selection of follow-up interventions.
Bullying and undermining behaviours in surgery: A qualitative study of surgical trainee experiences in the United Kingdom (UK) &amp; Republic of Ireland (ROI)
Authors: Joshua Michael Clements, Martin King, Rebecca Nicholas, Oliver Burdall, Elizabeth Elsey, Vittoria Bucknall, Ayoola Awopetu, Helen Mohan, Gemma Humm, Deirdre M. Nally
Journal: International Journal of Surgery (2020)
Drug Prices, Rebates, and Discounts
Authors: Benjamin N. Rome, William B. Feldman, Aaron S. Kesselheim
Journal: JAMA (2020)

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Potential False-Positive Meckel’s Scan Caused by Umbilical Ornamentation
Authors: Ravishankar Pillenahalli Maheshwarappa, Yusuf Menda
Journal: Clinical Nuclear Medicine (2020)

Abstract An 18-year-old woman presented to the emergency department for bloody stools. A CT scan of the abdomen ruled out intussusception. Meckel’s scan was ordered to rule for Meckel’s diverticulum before upper endoscopy and colonoscopy. After proper pretreatment with H 2 blocker, 99m Tc-pertechnetate Meckel’s scan was performed. Dynamic planar imaging revealed a focus of gradual increase in uptake in midabdomen suggestive of Meckel’s diverticulum. A SPECT/CT was done to localize the focus of uptake. Surprisingly, the focus of uptake localized to the periumbilical region on SPECT/CT images. The cause of uptake could be due to local inflammation from umbilical ornamentation.
Fundamentals of U.S. Health Policy — A Basic Training Perspective Series
Authors: Eric C. Schneider, Debra Malina, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

Interview with Dr. Eric Schneider on the policy challenges facing U.S. health care and opportunities for reform. (08:21)Download It has been said that every system is perfectly designed to get the results it gets. The strengths, weaknesses, flaws, and complexity of every health care system stem in large part from health policies. The U.S. health care system did not arise randomly but through a series of deliberate policy choices, many of which have come with unintended consequences. Efforts to reform our system over the past century reveal the ways in which Americans think the system has fallen short. They also reveal what we hope our health care system will do for us. Health policy — the choices made . . .
Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis
Authors: Young-Chang Kwon, Jiwoo Lim, So-Young Bang, Eunji Ha, Mi Yeong Hwang, Kyungheon Yoon, Jung-Yoon Choe, Dae-Hyun Yoo, Shin-Seok Lee, Jisoo Lee, Won Tae Chung, Tae-Hwan Kim, Yoon-Kyoung Sung, Seung-Cheol Shim, Chan-Bum Choi, Jae-Bum Jun, Young Mo Kang, Jung-Min Shin, Yeon-Kyung Lee, Soo-Kyung Cho, Bong-Jo Kim, Hye-Soon Lee, Kwangwoo Kim, Sang-Cheol Bae
Journal: Annals of the Rheumatic Diseases (2020)

Objective Genome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. As a continuous effort, we conducted GWAS in a large Korean RA case–control population. Methods We newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations. Results We identified six new RA-risk loci ( SLAMF6 , CXCL13 , SWAP70 , NFKBIA , ZFP36L1 and LINC00158 ) with p meta &lt;5×10 −8 and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases. Conclusion This study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.
PiggyBac mutagenesis and exome sequencing identify genetic driver landscapes and potential therapeutic targets of EGFR-mutant gliomas
Authors: Imran Noorani, Jorge de la Rosa, Yoon Ha Choi, Alexander Strong, Hannes Ponstingl, M. S. Vijayabaskar, Jusung Lee, Eunmin Lee, Angela Richard-Londt, Mathias Friedrich, Federica Furlanetto, Rocio Fuente, Ruby Banerjee, Fengtang Yang, Frances Law, Colin Watts, Roland Rad, George Vassiliou, Jong Kyoung Kim, Thomas Santarius, Sebastian Brandner, Allan Bradley
Journal: Genome biology (2020)

Abstract Background Glioma is the most common intrinsic brain tumor and also occurs in the spinal cord. Activating EGFR mutations are common in IDH1 wild-type gliomas. However, the cooperative partners of EGFR driving gliomagenesis remain poorly understood. Results We explore EGFR -mutant glioma evolution in conditional mutant mice by whole-exome sequencing, transposon mutagenesis forward genetic screening, and transcriptomics. We show mutant EGFR is sufficient to initiate gliomagenesis in vivo, both in the brain and spinal cord. We identify significantly recurrent somatic alterations in these gliomas including mutant EGFR amplifications and Sub1 , Trp53 , and Tead2 loss-of-function mutations. Comprehensive functional characterization of 96 gliomas by genome-wide piggyBac insertional mutagenesis in vivo identifies 281 known and novel EGFR -cooperating driver genes, including Cdkn2a , Nf1 , Spred1 , and Nav3 . Transcriptomics confirms transposon-mediated effects on expression of these genes. We validate the clinical relevance of new putative tumor suppressors by showing these are frequently altered in patients’ gliomas, with prognostic implications. We discover shared and distinct driver mutations in brain and spinal gliomas and confirm in vivo differential tumor suppressive effects of Pten between these tumors. Functional validation with CRISPR-Cas9-induced mutations in novel genes Tead2 , Spred1 , and Nav3 demonstrates heightened EGFRvIII -glioma cell proliferation. Chemogenomic analysis of mutated glioma genes reveals potential drug targets, with several investigational drugs showing efficacy in vitro. Conclusion Our work elucidates functional driver landscapes of EGFR -mutant gliomas, uncovering potential therapeutic strategies, and provides new tools for functional interrogation of gliomagenesis.