tbuckley/cabot-search huggingface dataset:
A CpG Methylation Classifier to Predict Relapse in Adults with T-Cell Lymphoblastic Lymphoma
Authors: Xiao-Peng Tian, Ning Su, Liang Wang, Wei-Juan Huang, Yan-Hui Liu, Xi Zhang, Hui-Qiang Huang, Tong-Yu Lin, Shu-Yun Ma, Hui-Lan Rao, Mei Li, Fang Liu, Fen Zhang, Li-Ye Zhong, Li Liang, Xiao-Liang Lan, Juan Li, Bing Liao, Zhi-Hua Li, Qiong-Lan Tang, Qiong Liang, Chun-Kui Shao, Qiong-Li Zhai, Run-Fen Cheng, Qi Sun, Kun Ru, Xia Gu, Xi-Na Lin, Kun Yi, Yue-Rong Shuang, Xiao-Dong Chen, Wei Dong, Cai Sun, Wei Sang, Hui Liu, Zhi-Gang Zhu, Jun Rao, Qiao-Nan Guo, Ying Zhou, Xiang-Ling Meng, Yong Zhu, Chang-Lu Hu, Yi-Rong Jiang, Ying Zhang, Hong-Yi Gao, Wen-Jun He, Zhong-Jun Xia, Xue-Yi Pan, Lan Hai, Guo-Wei Li, Li-Yan Song, Tie-Bang Kang, Dan Xie, Qing-Qing Cai
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. Experimental Design: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine–recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). Results: The four-CpG–based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P &amp;lt; 0.001). This classifier also showed good predictive value in the internal testing cohort (P &amp;lt; 0.001) and the independent validation cohort (P &amp;lt; 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. Conclusions: Our four-CpG–based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.
Cost-effectiveness Analysis of the Elder-Friendly Approaches to the Surgical Environment (EASE) Intervention for Emergency Abdominal Surgical Care of Adults Aged 65 Years and Older
Authors: Mark Hofmeister, Rachel G. Khadaroo, Jayna Holroyd-Leduc, Raj Padwal, Adrian Wagg, Lindsey Warkentin, Fiona Clement
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The Elder-Friendly Approaches to the Surgical Environment (EASE) initiative is a novel approach to acute surgical care for elderly patients. <h3>Objective</h3> To determine the cost-effectiveness of EASE. <h3>Design, Setting, and Participants</h3> An economic evaluation from the perspective of the health care system was conducted as part of the controlled before-and-after EASE study at 2 tertiary care centers, the University of Alberta Hospital and Foothills Medical Centre. Participants included elderly adults (aged ≥65 years) admitted for emergency abdominal surgery between 2014 and 2017. Data were analyzed from April 2018 to February 2019. <h3>Main Outcomes and Measures</h3> Data were captured at both control and intervention sites before and after implementation of the EASE intervention. Resource use was captured over 6 months of follow-up and was converted to costs. Utility was measured with the EuroQol Five-Dimensions Three-Levels instrument at 6 weeks and 6 months of follow-up. The differences-in-differences method was used to estimate the association of the intervention with cost and quality-adjusted life-years. For a subset of participants, self-reported out-of-pocket health care costs were collected using the Resource Use Inventory at 6 months. <h3>Results</h3> A total of 675 participants were included (mean [SD] age, 75.3 [7.9] years; 333 women [49.3%]), 289 in the intervention group and 386 in the control group. The mean (SD) cost per control participant was $36 995 ($44 169) before EASE and $35 032 ($43 611) after EASE (all costs are shown in 2018 Canadian dollars). The mean (SD) cost per intervention participant was $56 143 ($74 039) before EASE and $39 001 ($59 854) after EASE. Controlling for age, sex, and Clinical Frailty Score, the EASE intervention was associated with a mean (SE) cost reduction of 23.5% (12.5%) (<i>P</i> = .02). The change in quality-adjusted life-years observed associated with the intervention was not statistically significant (mean [SE], 0.00001 [0.0001] quality-adjusted life-year;<i>P</i> = .72). The Resource Use Inventory was collected for 331 participants. The mean (SE) odds ratio for having 0 out-of-pocket expenses because of the intervention, compared with having expenses greater than 0, was 15.77 (3.37) (<i>P</i> = .02). Among participants with Resource Use Inventory costs greater than 0, EASE was not associated with a change in spending (mean [SE] reduction associated with EASE, 19.1% [45.2%];<i>P</i> = .57). <h3>Conclusions and Relevance</h3> This study suggests that the EASE intervention was associated with a reduction in costs and no change in quality-adjusted life-years. In locations that lack capacity to implement this intervention, costs to increase capacity should be weighed against the estimated costs avoided.
A Physiological Point of View on Expiratory (Re)action during Mechanical Ventilation
Authors: Savino Spadaro, Carlo Alberto Volta
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

One of the most provocative observations is that, by stereology measures, smokers do not appear to have an increase in AM numbers.This is in conflict with studies demonstrating an increase in BAL macrophages from smokers (12).Interestingly, prior data support the authors' present observation, suggesting that the extent of the response in BAL was overrepresented by an analysis in lung tissue sections (13).Though not directly explored in this study, a possible explanation for these divergent findings is that AMs from smokers may be easier to lavage during BAL, thereby increasing their measured numbers.Alternatively, the authors identified that IMs were increased in smoker lung tissue, which appeared to be mostly due to an increase in macrophages in the alveolar septum.The role of the IMs in this setting were not clearly defined but these data do suggest the potential importance of defining IM function in exposure conditions like cigarette smoke and, ultimately, in disease states like chronic obstructive pulmonary disease.In total, this study continues to expand on our understanding of macrophages based on lung tissue location.It offers tantalizing insights into further tissue specification of macrophages and suggests that more work needs to be done, both to identify tools for isolation but also to focus on macrophage functions in these distinct regions.Ultimately, further work in these areas will allow the research community to truly grasp the diverse functional roles of macrophages with a goal of being able to tune these functions to limit tissue damage and/or injury and mitigate chronic lung disease.
Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012–2017
Authors: John A. Jernigan, Kelly M. Hatfield, Hannah Wolford, Richard E. Nelson, Babatunde Olubajo, Sujan C. Reddy, Natalie McCarthy, Prabasaj Paul, L. Clifford McDonald, Alex Kallen, Anthony Fiore, Michael Craig, James Baggs
Journal: New England Journal of Medicine (2020)

Multidrug-resistant (MDR) bacteria that are commonly associated with health care cause a substantial health burden. Updated national estimates for this group of pathogens are needed to inform public health action.
The electrocardiogram in the diagnosis and management of patients with dilated cardiomyopathy
Authors: Gherardo Finocchiaro, Marco Merlo, Nabeel Sheikh, Giulia De Angelis, Michael Papadakis, Iacopo Olivotto, Claudio Rapezzi, Gerald Carr‐White, Sanjay Sharma, Luisa Mestroni, Gianfranco Sinagra
Journal: European Journal of Heart Failure (2020)

Abstract The term dilated cardiomyopathy (DCM) defines a heterogeneous group of cardiac disorders, which are characterized by left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. In approximately one third of cases, DCM is familial with a genetic pathogenesis and various patterns of inheritance. Although the electrocardiogram (ECG) has been considered traditionally non‐specific in DCM, the recently acquired knowledge of the genotype–phenotype correlations provides novel opportunities to identify patterns and abnormalities that may point toward specific DCM subtypes. A learned ECG interpretation in combination with an appropriate use of other ECG‐based techniques including ambulatory ECG monitoring, exercise tolerance test and imaging modalities, such as echocardiography and cardiovascular magnetic resonance, may allow the early identification of specific genetic or acquired forms of DCM. Furthermore, ECG abnormalities may reflect the severity of the disease and provide a useful tool in risk stratification and management. In the present review, we discuss the current role of the ECG in the diagnosis and management of DCM. We describe various clinical settings where the appropriate use and interpretation of the ECG can provide invaluable clues, contributing to the important role of this basic tool as cardiovascular medicine evolves.
Ryanodine receptor subtypes regulate Ca2+ sparks/spontaneous transient outward currents and myogenic tone of uterine arteries in pregnancy
Authors: Rui Song, Xiang-Qun Hu, Monica Romero, Mark A Holguin, Whitney Kagabo, Daliao Xiao, Sean M Wilson, Lubo Zhang
Journal: Cardiovascular Research (2020)

Our recent study demonstrated that increased Ca2+ sparks and spontaneous transient outward currents (STOCs) played an important role in uterine vascular tone and haemodynamic adaptation to pregnancy. The present study examined the role of ryanodine receptor (RyR) subtypes in regulating Ca2+ sparks/STOCs and myogenic tone in uterine arterial adaptation to pregnancy.Uterine arteries isolated from non-pregnant and near-term pregnant sheep were used in the present study. Pregnancy increased the association of α and β1 subunits of large-conductance Ca2+-activated K+ (BKCa) channels and enhanced the co-localization of RyR1 and RyR2 with the β1 subunit in the uterine artery. In contrast, RyR3 was not co-localized with BKCa β1 subunit. Knockdown of RyR1 or RyR2 in uterine arteries of pregnant sheep downregulated the β1 but not α subunit of the BKCa channel and decreased the association of α and β1 subunits. Unlike RyR1 and RyR2, knockdown of RyR3 had no significant effect on either expression or association of BKCa subunits. In addition, knockdown of RyR1 or RyR2 significantly decreased Ca2+ spark frequency, suppressed STOCs frequency and amplitude, and increased pressure-dependent myogenic tone in uterine arteries of pregnant animals. RyR3 knockdown did not affect Ca2+ sparks/STOCs and myogenic tone in the uterine artery.Together, the present study demonstrates a novel mechanistic paradigm of RyR subtypes in the regulation of Ca2+ sparks/STOCs and uterine vascular tone, providing new insights into the mechanisms underlying uterine vascular adaptation to pregnancy.
ZBTB1 Regulates Asparagine Synthesis and Leukemia Cell Response to L-Asparaginase
Authors: Robert T. Williams, Rohiverth Guarecuco, Leah A. Gates, Douglas Barrows, Maria C. Passarelli, Bryce Carey, Lou Baudrier, Swarna Jeewajee, Konnor La, Benjamin Prizer, Sohail Malik, Javier Garcia-Bermudez, Xiphias Ge Zhu, Jason Cantor, Henrik Molina, Thomas Carroll, Robert G. Roeder, Omar Abdel-Wahab, C. David Allis, Kıvanç Birsoy
Journal: Cell Metabolism (2020)
The Influence of Cancer Molecular Subtypes and Treatment on the Mutation Spectrum in Metastatic Breast Cancers
Authors: Benjamin Verret, Tony Sourisseau, Bojana Stefanovska, Fernanda Mosele, Alicia Tran-Dien, Fabrice André
Journal: Cancer Research (2020)

Abstract Next-generation sequencing has sparked the exploration of cancer genomes, with the aim of discovering the genetic etiology of the disease and proposing rationally designed therapeutic interventions. Driver gene alterations have been comprehensively charted, but the improvement of cancer patient management somewhat lags behind these basic breakthroughs. Recently, large-scale sequencing that focused on metastasis, the main cause of cancer-related deaths, has shed new light on the driving forces at work during disease progression, particularly in breast cancer. Despite a fairly stable pool of driver genetic alterations between early and late disease, a number of therapeutically targetable mutations have been found enriched in metastatic samples. The molecular processes fueling disease progression have been delineated in recent studies and the clonal composition of breast cancer samples can be examined in detail. Here we discuss how these findings may be combined to improve the diagnosis of breast cancer to better select patients at risk, and to identify targeted agents to treat advanced diseases and to design therapeutic strategies exploiting vulnerabilities of cancer cells rooted in their ability to evolve and drive disease progression.
Immunomodulatory properties of lolium perenne peptides for the treatment of seasonal allergic rhinitis
Authors: JA Layhadi, H Sharif, I Singh, A Robb, L Kouser, R Parkin, U Sahiner, A Eifan, M Penagos Paniagua, G Vila-Nadal, H Rey-Garcia, Gabriële Holtappels, N Bovy, T Legon, S Pirotton, R Mösges, Claus Bachert, S Durham, M Shamji
Journal: Allergy (2019)
Deconstructing Pancreatic Adenocarcinoma by Targeting the Conductor, MYC
Authors: Isabel A. English, Rosalie C. Sears
Journal: Cancer Discovery (2020)

Abstract Summary: In this issue of Cancer Discovery, Sodir and colleagues employ a pancreatic ductal adenocarcinoma mouse model with mutant KRAS and inducible MYC to demonstrate that MYC acts as a reversible driver of malignant tumor progression. Abrogation of MYC triggers rapid regression and disassembly of the ensemble tumor through both cancer cell–intrinsic and cancer cell–extrinsic mechanisms, providing a compelling rationale for therapeutic targeting of MYC. See related article by Sodir et al., p. 588.
Long-term clinically relevant rodent model of methotrexate-induced cognitive impairment
Authors: Connor Berlin, Katharine Lange, H Carl Lekaye, Kelsey Hopland, Samantha Phillips, Jinghua Piao, Viviane Tabar
Journal: Neuro-Oncology (2020)

With the enhanced use of chemotherapy and the advent of increased patient survival rates, there are an increasing number of cancer survivors living with chemotherapy-induced cognitive impairment. A growing number of clinical studies have brought to light the association of agents like methotrexate in generating these neurological sequelae, although mechanisms remain unclear.Here, we use a clinically relevant regimen of several cycles of methotrexate and leucovorin rescue to develop a model of chemotherapy-induced cognitive impairment, and investigate the in vivo long-term (16 mo) impact of high-dose systemic methotrexate on white matter cellular dynamics as assessed by stereology, animal behavior, and diffusion tensor imaging.Our results indicate that at 6 and 16 months post-chemotherapy, methotrexate-treated rats exhibit a significant and permanent decrease in the number of oligodendrocytes and their progenitors in the white matter, in corpus callosum volumes, and myelin basic protein. These findings are associated with mostly delayed deficits in performance on Morris Water Maze and Novel Object Recognition tasks. Diffusion tensor imaging demonstrates significantly decreased fractional anisotropy values in the callosum genu, body, and splenium, as well as previously unassessed areas like the fimbria. Interestingly, these white matter changes are preceded by an earlier, transient decrement in white matter microglia at 3 months, and hippocampal neural progenitors at 3 and 6 months.These results demonstrate a significant negative impact of methotrexate on the oligodendrocyte compartment and white matter, associated with cognitive impairment. The data also support the use of diffusion tensor imaging in monitoring white matter integrity in this context.
Radiomics, Tumor Volume, and Blood Biomarkers for Early Prediction of Pseudoprogression in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibition
Authors: Lucas Basler, Hubert S. Gabryś, Sabrina A. Hogan, Matea Pavic, Marta Bogowicz, Diem Vuong, Stephanie Tanadini-Lang, Robert Förster, Ken Kudura, Martin W. Huellner, Reinhard Dummer, Matthias Guckenberger, Mitchell P. Levesque
Journal: Clinical Cancer Research (2020)

We assessed the predictive potential of positron emission tomography (PET)/CT-based radiomics, lesion volume, and routine blood markers for early differentiation of pseudoprogression from true progression at 3 months.112 patients with metastatic melanoma treated with immune checkpoint inhibition were included in our study. Median follow-up duration was 22 months. 716 metastases were segmented individually on CT and 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET imaging at three timepoints: baseline (TP0), 3 months (TP1), and 6 months (TP2). Response was defined on a lesion-individual level (RECIST 1.1) and retrospectively correlated with FDG-PET/CT radiomic features and the blood markers LDH/S100. Seven multivariate prediction model classes were generated.Two-year (median) overall survival, progression-free survival, and immune progression-free survival were 69% (not reached), 24% (6 months), and 42% (16 months), respectively. At 3 months, 106 (16%) lesions had progressed, of which 30 (5%) were identified as pseudoprogression at 6 months. Patients with pseudoprogressive lesions and without true progressive lesions had a similar outcome to responding patients and a significantly better 2-year overall survival of 100% (30 months), compared with 15% (10 months) in patients with true progressions/without pseudoprogression (P = 0.002). Patients with mixed progressive/pseudoprogressive lesions were in between at 53% (25 months). The blood prediction model (LDH+S100) achieved an AUC = 0.71. Higher LDH/S100 values indicated a low chance of pseudoprogression. Volume-based models: AUC = 0.72 (TP1) and AUC = 0.80 (delta-volume between TP0/TP1). Radiomics models (including/excluding volume-related features): AUC = 0.79/0.78. Combined blood/volume model: AUC = 0.79. Combined blood/radiomics model (including volume-related features): AUC = 0.78. The combined blood/radiomics model (excluding volume-related features) performed best: AUC = 0.82.Noninvasive PET/CT-based radiomics, especially in combination with blood parameters, are promising biomarkers for early differentiation of pseudoprogression, potentially avoiding added toxicity or delayed treatment switch.
Histopathologic Assessment of Capsular Invasion in Follicular Thyroid Neoplasms—an Observer Variation Study
Authors: Yun Zhu, Yaqiong Li, Chan Kwon Jung, Dong Eun Song, Jen-Fan Hang, Zhiyan Liu, Deepali Jain, Chiung-Ru Lai, Mitsuyoshi Hirokawa, Kennichi Kakudo, Andrey Bychkov
Journal: Endocrine Pathology (2020)
Prediction models for diagnosis and prognosis of covid-19: systematic review and critical appraisal
Authors: Laure Wynants, Ben Van Calster, Gary S Collins, Richard D Riley, Georg Heinze, Ewoud Schuit, Elena Albu, Banafsheh Arshi, Vanesa Bellou, Marc M J Bonten, Darren L Dahly, Johanna A Damen, Thomas P A Debray, Valentijn M T de Jong, Maarten De Vos, Paula Dhiman, Joie Ensor, Shan Gao, Maria C Haller, Michael O Harhay, Liesbet Henckaerts, Pauline Heus, Jeroen Hoogland, Mohammed Hudda, Kevin Jenniskens, Michael Kammer, Nina Kreuzberger, Anna Lohmann, Brooke Levis, Kim Luijken, Jie Ma, Glen P Martin, David J McLernon, Constanza L Andaur Navarro, Johannes B Reitsma, Jamie C Sergeant, Chunhu Shi, Nicole Skoetz, Luc J M Smits, Kym I E Snell, Matthew Sperrin, René Spijker, Ewout W Steyerberg, Toshihiko Takada, Ioanna Tzoulaki, Sander M J van Kuijk, Bas C T van Bussel, Iwan C C van der Horst, Kelly Reeve, Florien S van Royen, Jan Y Verbakel, Christine Wallisch, Jack Wilkinson, Robert Wolff, Lotty Hooft, Karel G M Moons, Maarten van Smeden
Journal: BMJ (2020)

To review and appraise the validity and usefulness of published and preprint reports of prediction models for diagnosing coronavirus disease 2019 (covid-19) in patients with suspected infection, for prognosis of patients with covid-19, and for detecting people in the general population at increased risk of covid-19 infection or being admitted to hospital with the disease.
Acral Purpura in Dermatitis Herpetiformis
Authors: Alejandro García-Vázquez, Santiago Guillen-Climent, María Isabel Pinazo-Canales
Journal: JAMA Dermatology (2020)

This case report describes a 32-year-old woman with pruritic, small vesicles and papules on the eyelids, elbows, knees, buttocks, and scalp, as well as reddish-brown hemorrhagic lesions on the palms, soles, and volar surface of the fingers.