bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival prediction in mesothelioma using a scalable Lasso regression model: instructions for use and initial performance using clinical predictors
Authors: Kidd Andrew C , McGettrick Michael , Tsim Selina , Halligan Daniel L , Bylesjo Max , Blyth Kevin G 
Published: January 2018

IntroductionAccurate prognostication is difficult in malignant pleural mesothelioma (MPM). We developed a set of robust computational models to quantify the prognostic value of routinely available clinical data, which form the basis of published MPM prognostic models.MethodsData regarding 269 patients with MPM were allocated to balanced training (n=169) and validation sets (n=100). Prognostic signatures (minimal length best performing multivariate trained models) were generated by least absolute shrinkage and selection operator regression for overall survival (OS), OS <6 months and OS <12 months. OS prediction was quantified using Somers DXYstatistic, which varies from 0 to 1, with increasing concordance between observed and predicted outcomes. 6-month survival and 12-month survival were described by area under the curve (AUC) scores.ResultsMedian OS was 270 (IQR 140–450) days. The primary OS model assigned high weights to four predictors: age, performance status, white cell count and serum albumin, and after cross-validation performed significantly better than would be expected by chance (mean DXY0.332 (±0.019)). However, validation set DXYwas only 0.221 (0.0935–0.346), equating to a 22% improvement in survival prediction than would be expected by chance. The 6-month and 12-month OS signatures included the same four predictors, in addition to epithelioid histology plus platelets and epithelioid histology plus C-reactive protein (mean AUC 0.758 (±0.022) and 0.737 (±0.012), respectively). The <6-month OS model demonstrated 74% sensitivity and 68% specificity. The <12-month OS model demonstrated 63% sensitivity and 79% specificity. Model content and performance were generally comparable with previous studies.ConclusionsThe prognostic value of the basic clinical information contained in these, and previously published models, is fundamentally of limited value in accurately predicting MPM prognosis. The methods described are suitable for expansion using emerging predictors, including tumour genomics and volumetric staging.
Development of a patient-centred, evidence-based and consensus-based discharge care bundle for patients with acute exacerbation of chronic obstructive pulmonary disease
Authors: Ospina Maria B , Michas Marta , Deuchar Lesly , Leigh Richard , Bhutani Mohit , Rowe Brian H , Marciniuk Darcy , Goodridge Donna , Dechman Gail , Bourbeau Jean , Balter Meyer , Camp Pat , Hernandez Paul , Goldstein Roger S , Stickland Michael K 
Published: January 2018

IntroductionHospital and emergency department discharge for patients with chronic obstructive pulmonary disease (COPD) is often poorly organised. We developed a patient-centred, evidence-based and consensus-based discharge care bundle for patients with acute exacerbations of COPD.MethodsA purposeful sample of clinicians and patients were invited to participate in a two-round Delphi study (July–November 2015). In round 1, participants rated on a seven-point Likert scale (1=not at all important; 7=extremely important) the importance of 29 unique COPD care actions. Round 2 comprised items selected from round 1 based on consensus (>80% endorsement for Likert values 5–7). A list of 18 care items from round 2 was discussed in a face-to-face nominal group meeting.ResultsSeven care items were included in the COPD discharge bundle based on clinician and patient input: (1) ensure adequate inhaler technique is demonstrated; (2) send discharge summary to family physician and arrange follow-up; (3) optimise and reconcile prescription of respiratory medications; (4) provide a written discharge management plan and assess patient’s and caregiver’s comprehension of discharge instructions; (5) refer to pulmonary rehabilitation; (6) screen for frailty and comorbidities; and (7) assess smoking status, provide counselling and refer to smoking cessation programme.ConclusionWe present a seven-item, patient-centred, evidence-based and consensus-based discharge bundle for patients with acute exacerbations of COPD. Alignment with clinical practice guidelines and feasibility of local adaptations of the bundle should be explored to facilitate wide applicability and evaluation of the effectiveness of the COPD discharge bundle.
Media Lab Asia: Renovating Business Model for Underserved
Authors: Kumar Subhash 
Published: January 2018

Media Lab Asia (MLA) has been incepted in 2001 with the collaboration of MIT Media Lab and Department of Electronics & Information Technology (DEITY), Government of India. It is working on the paradigm of collaborative research from the lab to land in developing and operationalizing technologies to bridge the gap through educating, equipping and empowering common man. MLA is working in four sectors: livelihood, healthcare, empowerment of the disabled and education. MLA is successful in collaborating with Research & Development (R&D) organizations, institutions in Government, Non-Governmental Organizations (NGOs), academia and industry. A long list of collaborators of MLA includes 59 partner agencies. MLA role, however, had confined to provide funding to the partner agencies. The collaborative organization develops product, tests and launches the projects. The reach of the project touches major states in India. eGalla, Chic, mDhanwanthari, and Sehat-Saathi are some of the projects developed by MLA and collaborators. eGalla is a retail management software, and Chic is developed to simplify the traditional craft for livelihood generation. mDhanwanthari and Sehat-Saathi are based on healthcare to rural communities. MLA has developed 75 projects since its inception. The projects have reached the beneficiary but lack in scale and commercialization. The parameter of success for MLA includes the potential for commercialization of the products or projects and self-sustaining mechanism of the impact of these products and projects. There are not many obligations for commercial success being a Section 25 company; however, a self-sustaining mechanism was critical. DEITY, the parent organization, has sought external support to develop a new business model to overcome the limitation.
Similar nicotinic excitability responses across the developing hippocampal formation are regulated by small-conductance calcium-activated potassium channels
Authors: Chung Beryl Y.T. , Bailey Craig D.C. 
Published: January 2018

The hippocampal formation forms a cognitive circuit that is critical for learning and memory. Cholinergic input to nicotinic acetylcholine receptors plays an important role in the normal development of principal neurons within the hippocampal formation. However, the ability of nicotinic receptors to stimulate principal neurons across all regions of the developing hippocampal formation has not been determined. We show in this study that heteromeric nicotinic receptors mediate direct inward current and depolarization responses in principal neurons across the hippocampal formation of the young postnatal mouse. These responses were found in principal neurons of the CA1, CA3, dentate gyrus, subiculum, and entorhinal cortex layer VI, and they varied in magnitude across regions with the greatest responses occurring in the subiculum and entorhinal cortex. Despite this regional variation in the magnitude of passive responses, heteromeric nicotinic receptor stimulation increased the excitability of active principal neurons by a similar amount in all regions. Pharmacological experiments found this similar excitability response to be regulated by small-conductance calcium-activated potassium (SK) channels, which exhibited regional differences in their influence on neuron activity that offset the observed regional differences in passive nicotinic responses. These findings demonstrate that SK channels play a role to coordinate the magnitude of heteromeric nicotinic excitability responses across the hippocampal formation at a time when nicotinic signaling drives the development of this cognitive brain region. This coordinated input may contribute to the normal development, synchrony, and maturation of the hippocampal formation learning and memory network. NEW & NOTEWORTHY This study demonstrates that small-conductance calcium-activated potassium channels regulate similar-magnitude excitability responses to heteromeric nicotinic acetylcholine receptor stimulation in active principal neurons across multiple regions of the developing mouse hippocampal formation. Given the importance of nicotinic neurotransmission for the development of principal neurons within the hippocampal formation, this coordinated excitability response is positioned to influence the normal development, synchrony, and maturation of the hippocampal formation learning and memory network.
Analysis of variability in length of sleep state bouts reveals memory-free sleep subcomponents consistent among primary insomnia patients
Authors: Bizzotto Roberto , Zamuner Stefano 
Published: January 2018

The statistical distributions of bout lengths for the different (macro) sleep states (wake, N1, N2, N3, and REM sleep) are essential to understanding whether any memory-free subcomponent (“micro state”) is involved in the organization of sleep. Micro state detection can be prevented by the fusion of data including various sources of variability, in particular by the differences in sleep architecture between individuals, along sleep time (or nighttime), or between different nights. In this analysis, a mathematical model of sleep was adopted to disentangle these features and advance the understanding of the dynamics and mechanisms of sleep and its states. The analysis involved 116 primary insomnia patients taking placebo before going to bed and undergoing polysomnography for one night. The individual sequences of macro sleep states had been previously modeled with a mixed-effect nonhomogeneous modified Markov chain model, from which individual conditional probability distributions for the bout durations were derived in this analysis as functions of sleep time. The probability distributions, affected by neither subject, night-time, nor multiple-night pooling, substantially changed at ¼ and ¾ sleep time, had modified exponential shape, and were best described as the sum of one to four exponentials, depending on the sleep state. The time constants and proportions of bouts contributing to each exponential were similar in the different subjects, changing over sleep time. Variability in bout durations thus indicated the presence of multiple memory-free sleep subcomponents whose mean residence times and access probabilities could be identified and shown to be consistent among the studied subjects.NEW & NOTEWORTHY We present a new methodology for deriving, from polysomnography data, the individual conditional probability for the duration of the bouts of wake, N1, N2, N3, and REM sleep. We evaluated the variability of this probability within and between primary insomnia patients and along sleep time. The multiexponential shapes of the probability distributions within the individuals revealed memory-free mechanisms and sleep subcomponents with consistent features in the studied population.
Splenic Abscess: An Uncommon Entity with Potentially Life-Threatening Evolution
Authors: Lee Mei-Chun , Lee Chun-Ming 
Published: January 2018

Background/Purpose. Splenic abscess is rare with potentially life-threatening evolution. The aim of this study is to review the clinical features, microbiological etiologies, treatment, and outcomes of patients with splenic abscess. Methods. We reviewed the admitted patients with suspected splenic abscess and made the diagnosis of splenic abscess. The clinical characteristics, underlying diseases, treatment course, organism spectra, abscess number and size, therapeutic methods, and clinical outcome at a tertiary medical center in Taiwan over a period of 5 years were analyzed. Results. Of 16 patients with splenic abscess, the male to female ratio was 1 : 1. Common presentations were fever (11 patients, 68.7%), diffuse abdominal pain (6 patients, 37.5%), left upper quadrant pain or tenderness (6 patients, 37.5%), and left-sided pleural effusions (8 patients, 50%). Antimicrobial therapy was administered in all patients. Fourteen (87.5%) patients recovered under medical treatment. One (6.2%) patient underwent splenectomy, four (25%) patients performed percutaneous drainage of their splenic abscess, and 11 (68.7%) patients received antimicrobial therapy alone. Conclusion. We noted that mortality may be more related to patients with underlying immunodeficiency. Patients with splenic abscesses receiving antimicrobial therapy alone were in a relatively high proportion and got a good prognosis especially in patients with small and multiple abscesses.
Antitumor T-cell Reconditioning: Improving Metabolic Fitness for Optimal Cancer Immunotherapy
Authors: Rivadeneira Dayana B. , Delgoffe Greg M. 
Published: January 2018

Abstract
With the rapid rise of immunotherapy for cancer treatment, attention has focused on gaining a better understanding of T-cell biology in the tumor microenvironment. Elucidating the factors underlying changes in their function will allow for the development of new therapeutic strategies that could expand the patient population benefiting from immunotherapy, as well as circumvent therapy resistance. Cancers go beyond avoiding immune recognition and inducing T-cell dysfunction through coinhibitory molecules. Recent work has demonstrated that the tumor microenvironment elicits metabolic changes in T cells that dampen their ability to respond and that manipulating these metabolic changes can strengthen an antitumor immune response. Here we review the metabolic status of various types of T cells, the energetic state of the tumor microenvironment, and proposed modalities for improvement of immunotherapy through metabolic remodeling. Clin Cancer Res; 24(11); 2473–81. ©2018 AACR.
Metastasis Seeding Cells: Lone Invaders or Mass Migrators?
Authors: Gerlinger Marco 
Published: January 2018

Abstract
Lymph node metastases are among the best predictors of recurrence and of cancer-related death in early-stage colorectal cancers. Yet, despite their clinical and biological relevance, it remains elusive how lymph node metastases develop and whether metastatic seeding is a major bottleneck that restrains genetic heterogeneity of metastatic disease. Clin Cancer Res; 24(9); 2032–4. ©2018 AACR.
See related article by Ulintz et al., p. 2214
Single-Cell Sequencing of the Healthy and Diseased Heart Reveals Cytoskeleton-Associated Protein 4 as a New Modulator of Fibroblasts Activation
Authors: Gladka Monika M. , Molenaar Bas , de Ruiter Hesther , van der Elst Stefan , Tsui Hoyee , Versteeg Danielle , Lacraz Grègory P.A. , Huibers Manon M.H. , van Oudenaarden Alexander , van Rooij Eva 
Published: January 2018

Background:
Genome-wide transcriptome analysis has greatly advanced our understanding of the regulatory networks underlying basic cardiac biology and mechanisms driving disease. However, so far, the resolution of studying gene expression patterns in the adult heart has been limited to the level of extracts from whole tissues. The use of tissue homogenates inherently causes the loss of any information on cellular origin or cell type-specific changes in gene expression. Recent developments in RNA amplification strategies provide a unique opportunity to use small amounts of input RNA for genome-wide sequencing of single cells.

Methods:
Here, we present a method to obtain high-quality RNA from digested cardiac tissue from adult mice for automated single-cell sequencing of both the healthy and diseased heart.

Results:
After optimization, we were able to perform single-cell sequencing on adult cardiac tissue under both homeostatic conditions and after ischemic injury. Clustering analysis based on differential gene expression unveiled known and novel markers of all main cardiac cell types. Based on differential gene expression, we could identify multiple subpopulations within a certain cell type. Furthermore, applying single-cell sequencing on both the healthy and injured heart indicated the presence of disease-specific cell subpopulations. As such, we identified cytoskeleton-associated protein 4 as a novel marker for activated fibroblasts that positively correlates with known myofibroblast markers in both mouse and human cardiac tissue. Cytoskeleton-associated protein 4 inhibition in activated fibroblasts treated with transforming growth factor β triggered a greater increase in the expression of genes related to activated fibroblasts compared with control, suggesting a role of cytoskeleton-associated protein 4 in modulating fibroblast activation in the injured heart.

Conclusions:
Single-cell sequencing on both the healthy and diseased adult heart allows us to study transcriptomic differences between cardiac cells, as well as cell type-specific changes in gene expression during cardiac disease. This new approach provides a wealth of novel insights into molecular changes that underlie the cellular processes relevant for cardiac biology and pathophysiology. Applying this technology could lead to the discovery of new therapeutic targets relevant for heart disease.
Inhibition of 5‐Hydroxytryptamine Receptor 2B Reduced Vascular Restenosis and Mitigated the β‐Arrestin2–Mammalian Target of Rapamycin/p70S6K Pathway
Authors: Liu Yahan , Wang Zhipeng , Li Jing , Ban Yiqian , Mao Guangmei , Zhang Man , Wang Mo , Liu Yan , Zhao Beilei , Shen Qiang , Xu Qingbo , Wang Nanping 
Published: January 2018

Background
As a monoamine neurotransmitter, 5‐hydroxytryptamine (5‐HT) or serotonin modulates mood, appetite, and sleep. Besides, 5‐HT also has important peripheral functions. 5‐HT receptor 2B (5‐HT2BR) plays a key role in cardiovascular diseases, such as pulmonary arterial hypertension and cardiac valve disease. Percutaneous intervention has been used to restore blood flow in occlusive vascular disease. However, restenosis remains a significant problem. Herein, we investigated the role of 5‐HT2BR in neointimal hyperplasia, a key pathological process in restenosis.

Methods and Results

The expression of 5‐HT2BR was upregulated in wire‐injured mouse femoral arteries. In addition, BW723C86, a selective 5‐HT2BR agonist, promoted the injury response during restenosis. 5‐HT and BW723C86 stimulated migration and proliferation of rat aortic smooth muscle cells. Conversely, LY272015, a selective antagonist, attenuated the 5‐HT–induced smooth muscle cell migration and proliferation. In vitro study showed that the promigratory effects of 5‐HT2BR were mediated through the activation of mammalian target of rapamycin (mTOR)/p70S6K signaling in a β‐arrestin2–dependent manner. Inhibition of mammalian target of rapamycin or p70S6K mitigated 5‐HT2BR–mediated smooth muscle cell migration. Mice with deficiency of
5‐HT2BR
showed significantly reduced neointimal formation in wire‐injured arteries.

Conclusions
These results demonstrated that activation of 5‐HT2BR and β‐arrestin2–biased downstream signaling are key pathological processes in neointimal formation, and 5‐HT2BR may be a potential target for the therapeutic intervention of vascular restenosis.
Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis
Authors: Budatha Madhusudhan , Zhang Jiasheng , Zhuang Zhen W. , Yun Sanguk , Dahlman James E. , Anderson Daniel G. , Schwartz Martin A. 
Published: January 2018

Background
Fibronectin in endothelial basement membranes promotes endothelial inflammatory activation and atherosclerosis but also promotes plaque stability and vascular remodeling. The fibronectin receptor α5 subunit is proinflammatory through binding to and activating phosphodiesterase 4D5, which inhibits anti‐inflammatory cyclic adenosine monophosphate and protein kinase A. Replacing the α5 cytoplasmic domain with that of α2 resulted in smaller atherosclerotic plaques. Here, we further assessed plaque phenotype and compensatory vascular remodeling in this model.

Methods and Results

α5/2 mice in the hyperlipidemic apolipoprotein E null background had smaller plaques in the aortic root, with reduced endothelial
NF
‐κB activation and inflammatory gene expression, reduced leukocyte content, and much lower metalloproteinase expression. However, smooth muscle cell content, fibrous cap thickness, and fibrillar collagen were unchanged, indicating no shift toward vulnerability. In vivo knockdown of phosphodiesterase 4D5 also decreased endothelial inflammatory activation and atherosclerotic plaque size. α5/2 mice showed improved recovery from hindlimb ischemia after femoral artery ligation.

Conclusions
Blocking the fibronectin‐Integrin α5 pathway reduces atherosclerotic plaque size, maintains plaque stability, and improves compensatory remodeling. This pathway is therefore a potential therapeutic target for treatment of atherosclerosis.
Development of a Comprehensive Quality-of-Life Measure for Facial and Torso Acne
Authors: McLellan Chelsea , Frey Marc P. , Thiboutot Diane , Layton Alison , Chren Mary-Margaret , Tan Jerry 
Published: January 2018

Background Acne is a chronic skin disorder which generally presents in adolescence but continues into adulthood, and negatively affects both physical and psychosocial well-being. Presently, there are no validated acne-specific quality-of-life (QoL) measures that include dimensions for both facial and torso acne. Objective: The objective of this study was to develop a QoL instrument for both facial and torso acne (CompAQ) in accordance with recommended standards. Methods: A literature review and Delphi survey of patients and clinicians were used to develop the conceptual framework for outcomes perceived important to acne patients. An initial version of the measure was developed, CompAQ-v1, and pilot tested with patients via cognitive interviews. Results: The Delphi survey generated 4 domains (physical, psychological, sociological, and treatment) and 54 items. These, along with a literature review and input from clinical experts, informed the development of the CompAQ-v1. Eleven cognitive interviews were conducted, resulting in the second version of the measure, CompAQ-v2. Psychometric validation resulted in the final 20-item CompAQ measure comprising 5 domains. An abbreviated 5-item measure was also developed (CompAQ-SF). Conclusion: CompAQ and CompAQ-SF are instruments intended to evaluate QoL in patients with acne on their face or torso. The former is a 21-item QoL intended for research, while the latter is intended for clinical practice.