bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of tacrolimus and vedolizumab after corticosteroid and anti-TNF failure in paediatric severe colitis
Authors: Hamel Blaise , Wu May , Hamel Elizabeth O , Bass Dorsey M , Park K T 
Published: February 2018

BackgroundSevere colitis flare from ulcerative colitis (UC) or Crohn’s disease (CD) may be refractory to corticosteroids and antitumour necrosis factor (TNF) agents resulting in high colectomy rates. We aimed to describe the utility of tacrolimus to prevent colectomy during second-line vedolizumab initiation after corticosteroid and anti-TNF treatment failure in paediatric severe colitis.MethodsA retrospective cohort analysis was performed between 1 October 2014 and 31 October 2016 at a single tertiary care centre. Inclusion criteria were patients with severe colitis who received tacrolimus before or during vedolizumab induction and previous exposure to anti-TNF therapy with or without corticosteroids. The initiation of tacrolimus was clinician dependent based on an institutional protocol.ResultsTwelve patients (10 UC, two CD; median age 16 years; three female) received at least one dose of vedolizumab 10 mg/kg (max of 300 mg) due to anti-TNF therapy failure and persistent flare not responsive to corticosteroids. Of the 12 patients, eight (67%) and four (33%) had failed one or two anti-TNF agents, respectively. Tacrolimus was initiated for acute disease severity during hospitalisation (58%) or ongoing flare during outpatient care (42%). 9 (75%) of 12 patients avoided colectomy or inflammatory bowel disease-related surgery at 24 weeks and eight (68%) continued on vedolizumab maintenance with no adverse events out to 80 weeks.ConclusionWe report real-world data on the outcome of tacrolimus around vedolizumab initiation in paediatric UC or CD after corticosteroid and anti-TNF therapy treatment failure. Our pilot experience indicates a potential benefit of concomitant tacrolimus when initiating vedolizumab therapy.
Remote biomonitoring of temperatures in mothers and newborns: design, development and testing of a wearable sensor device in a tertiary-care hospital in southern India
Authors: Mony Prem K , Thankachan Prashanth , Bhat Swarnarekha , Rao Suman , Washington Maryann , Antony Sumi , Thomas Annamma , Nagarajarao Sheela C , Rao Hiteshwar , Amrutur Bharadwaj 
Published: February 2018

ObjectiveNewer technologies such as wearables, sensors, mobile telephony and computing offer opportunities to monitor vital physiological parameters and tackle healthcare problems, thereby improving access and quality of care. We describe the design, development and testing of a wearable sensor device for remote biomonitoring of body temperatures in mothers and newborns in southern India.MethodsBased on client needs and technological requirements, a wearable sensor device was designed and developed using principles of ‘social innovation’ design. The device underwent multiple iterations in product design and engineering based on user feedback, and then following preclinical testing, a techno-feasibility study and clinical trial were undertaken in a tertiary-care teaching hospital in Bangalore, India. Clinical trial phases I and IIa for evaluation of safety and efficacy were undertaken in the following sequence: 7 healthy adult volunteers; 18 healthy mothers; 3 healthy babies; 10 stable babies in the neonatal care intensive unit and 1 baby with morbidities. Time-stamped skin temperature readings obtained at 5 min intervals over a 1-hour period from the device secured on upper arms of mothers and abdomen of neonates were compared against readings from thermometers used routinely in clinical practice.ResultsDevices were comfortably secured on to adults and neonates, and data were efficiently transmitted via the gateway device for secure storage and retrieval for analysis. The mean skin temperatures in mothers were lower than the axillary temperatures by 2°C; and in newborns, there was a precision of –0.5°C relative to axillary measurements. While occasional minimal adverse events were noted in healthy volunteers, no adverse events were noted in mothers or neonates.ConclusionsThis proof-of-concept study shows that this device is promising in terms of feasibility, safety and accuracy (with appropriate calibration) with potential for further refinements in device accuracy and pursuit of further phases of clinical research for improved maternal and neonatal health.
Feasibility, acceptability and effectiveness of an online alternative to face-to-face consultation in general practice: a mixed-methods study of webGP in six Devon practices
Authors: Carter Mary , Fletcher Emily , Sansom Anna , Warren Fiona C , Campbell John L 
Published: February 2018

ObjectivesTo evaluate the feasibility, acceptability and effectiveness of webGP as piloted by six general practices.MethodsMixed-methods evaluation, including data extraction from practice databases, general practitioner (GP) completion of case reports, patient questionnaires and staff interviews.SettingGeneral practices in NHS Northern, Eastern and Western Devon Clinical Commissioning Group’s area approximately 6 months after implementing webGP (February–July 2016).ParticipantsSix practices provided consultations data; 20 GPs completed case reports (regarding 61 e-consults); 81 patients completed questionnaires; 5 GPs and 5 administrators were interviewed.Outcome measuresAttitudes and experiences of practice staff and patients regarding webGP.ResultsWebGP uptake during the evaluation was small, showing no discernible impact on practice workload. The completeness of cross-sectional data on consultation workload varied between practices.GPs judged 41/61 (72%) of webGP requests to require a face-to-face or telephone consultation. Introducing webGP appeared to be associated with shifts in responsibility and workload between practice staff and between practices and patients.81/231 patients completed a postal survey (35.1% response rate). E-Consulters were somewhat younger and more likely to be employed than face-to-face respondents. WebGP appeared broadly acceptable to patients regarding timeliness and quality/experience of care provided. Similar problems were presented by all respondents. Both groups appeared equally familiar with other practice online services; e-consulters were somewhat more likely to have used them.From semistructured staff interviews, it appeared that, while largely acceptable within practice, introducing e-consults had potential for adverse interactions with pre-existing practice systems.ConclusionsThere is potential to assess the impact of new systems on consultation patterns by extracting routine data from practice databases. Staff and patients noticed subtle changes to responsibilities associated with online options. Greater uptake requires good communication between practice and patients, and organisation of systems to avoid conflicts and misuse. Further research is required to evaluate the full potential of webGP in managing practice workload.
Postmatch recovery of physical performance and biochemical markers in team ball sports: a systematic review
Authors: Doeven Steven H , Brink Michel S , Kosse Silke J , Lemmink Koen A P M 
Published: February 2018

BackgroundInsufficient postmatch recovery in elite players may cause an increased risk of injuries, illnesses and non-functional over-reaching.ObjectiveTo evaluate postmatch recovery time courses of physical performance and biochemical markers in team ball sport players.Study designSystematic review.Data sourcesPubMed and Web of Science.Eligibility criteria for selecting studiesThis systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Critical Review Form for Quantitative Studies was used to evaluate quality. Studies were included if they met the following criteria: (1) original research evaluated players’ physical recovery postmatch; (2) team/intermittent sports; and (3) at least two postmeasurements were compared with baseline values.ResultsTwenty-eight studies were eligible. Mean methodological quality was 11.2±1.11. Most used performance tests and biochemical markers were the countermovement jump test, sprint tests and creatine kinase (CK), cortisol (C) and testosterone (T), respectively.Summary/conclusionsThe current evidence demonstrates that underlying mechanisms of muscle recovery are still in progress while performance recovery is already reached. CK recovery time courses are up to ≥72 hours. Soccer and rugby players need more time to recover for sprint performance, CK and C in comparison to other team ball sports. There are more high-quality studies needed regarding recovery in various team sports and recovery strategies on an individual level should be evaluated.Clinical relevanceOngoing insufficient recovery can be prevented by the use of the presented recovery time courses as specific practical recovery guidelines.
Association between short sleep duration and carotid atherosclerosis modified by age in a Chinese community population
Authors: Chen Si , Yang Ying , Cheng Guan-Liang , Jia Jia , Fan Fang-Fang , Li Jian-Ping , Huo Yong , Zhang Yan , Chen Da-Fang 
Published: February 2018

Background and aimShort sleep duration is a risk factor of cardiovascular disorder; however, the association between short sleep duration and carotid atherosclerosis has not been completely characterised. The aim of this study is to investigate the association between short sleep duration and carotid atherosclerosis.MethodsWe used the cross-sectional data collected between May 2014 and July 2014, which were based on a cardiovascular disease cohort study including 3798 participants aged 40 years and older who are residents of Beijing, China. We used logistic regression models to examine the associations between sleep duration and carotid atherosclerosis.ResultsAfter the adjustment of covariates, short sleep duration (less than 5 hours per night) was found to be associated with carotid atherosclerosis, and it also elevated the risk of, in both terms, the increment of prevalence (OR=1.31, P<0.05) and the quantity of carotid plaques (OR=1.28, P<0.05). When age was also taken into consideration, the largest association, in both terms of prevalence (OR=3.46, P<0.01) and the number of carotid plaques (OR=4.23, P<0.01), was found in subjects over the age of 60 with short sleep duration.ConclusionIn conclusion, sleep duration less than 5 hours per night is associated with a higher risk of carotid atherosclerosis compared with subjects who sleeps for 5 or over 5 hours per night, and the association may be modified by age.
cGAS-mediated autophagy protects the liver from ischemia-reperfusion injury independently of STING
Authors: Lei Zhao , Deng Meihong , Yi Zhongjie , Sun Qian , Shapiro Richard A. , Xu Hongbo , Li Tunliang , Loughran Patricia A. , Griepentrog John E. , Huang Hai , Scott Melanie J. , Huang Feizhou , Billiar Timothy R. 
Published: February 2018

Liver ischemia-reperfusion (I/R) injury occurs through induction of oxidative stress and release of damage-associated molecular patterns (DAMPs), including cytosolic DNA released from dysfunctional mitochondria or from the nucleus. Cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) synthase (cGAS) is a cytosolic DNA sensor known to trigger stimulator of interferon genes (STING) and downstream type 1 interferon (IFN-I) pathways, which are pivotal innate immune system responses to pathogen. However, little is known about the role of cGAS/STING in liver I/R injury. We subjected C57BL/6 (WT), cGAS knockout (cGAS−/−), and STING-deficient (STINGgt/gt) mice to warm liver I/R injury and that found cGAS−/− mice had significantly increased liver injury compared with WT or STINGgt/gt mice, suggesting a protective effect of cGAS independent of STING. Liver I/R upregulated cGAS in vivo and also in vitro in hepatocytes subjected to anoxia/reoxygenation (A/R). We confirmed a previously published finding that hepatocytes do not express STING under normoxic conditions or after A/R. Hepatocytes and liver from cGAS−/− mice had increased cell death and reduced induction of autophagy under hypoxic conditions as well as increased apoptosis. Protection could be restored in cGAS−/− hepatocytes by overexpression of cGAS or by pretreatment of mice with autophagy inducer rapamycin. Our findings indicate a novel protective role for cGAS in the regulation of autophagy during liver I/R injury that occurs independently of STING. NEW & NOTEWORTHY Our studies are the first to document the important role of cGAS in the acute setting of sterile injury induced by I/R. Specifically, we provide evidence that cGAS protects liver from I/R injury in a STING-independent manner.
Measures of sympathetic and parasympathetic autonomic outflow from heartbeat dynamics
Authors: Valenza Gaetano , Citi Luca , Saul J. Philip , Barbieri Riccardo 
Published: February 2018

Reliable and effective noninvasive measures of sympathetic and parasympathetic peripheral outflow are of crucial importance in cardiovascular physiology. Although many techniques have been proposed to take up this long-lasting challenge, none has proposed a satisfying discrimination of the dynamics of the two separate branches. Spectral analysis of heart rate variability is the most currently used technique for such assessment. Despite its widespread use, it has been demonstrated that the subdivision in the low-frequency (LF) and high-frequency (HF) bands does not fully reflect separate influences of the sympathetic and parasympathetic branches, respectively, mainly due to their simultaneous action in the LF. Two novel heartbeat-derived autonomic measures, the sympathetic activity index (SAI) and parasympathetic activity index (PAI), are proposed to separately assess the time-varying autonomic nervous system synergic functions. Their efficacy is validated in landmark autonomic maneuvers generally employed in clinical settings. The novel measures move beyond the classical frequency domain paradigm through identification of a set of coefficients associated with a proper combination of Laguerre base functions. The resulting measures were compared with the traditional LF and HF power. A total of 236 ECG recordings were analyzed for validation, including autonomic outflow changes elicited by procedures of different nature and temporal variation, such as postural changes, lower body negative pressure, and handgrip tests. The proposed SAI-PAI measures consistently outperform traditional frequency-domain indexes in tracking expected instantaneous autonomic variations, both vagal and sympathetic, and may aid clinical decision making, showing reduced intersubject variability and physiologically plausible dynamics. NEW & NOTEWORTHY While it is possible to obtain reliable estimates of parasympathetic activity from the ECG, a satisfying method to disentangle the sympathetic component from HRV has not been proposed yet. To overcome this long-lasting limitation, we propose two novel HRV-based indexes, the sympathetic and parasympathetic activity indexes.
Blunted shear-mediated dilation of the internal but not common carotid artery in response to lower body negative pressure
Authors: Iwamoto Erika , Bock Joshua M. , Casey Darren P. 
Published: February 2018

Shear-mediated dilation in peripheral conduit arteries is blunted with sympathetic nervous system (SNS) activation; however, the effect of SNS activation on shear-mediated dilation in carotid arteries is unknown. We hypothesized that SNS activation reduces shear-mediated dilation in common and internal carotid arteries (CCA and ICA, respectively), and this attenuation is greater in the ICA compared with the CCA. Shear-mediated dilation in the CCA and ICA were measured in nine healthy men (24 ± 1 yr) with and without SNS activation. Shear-mediated dilation was induced by 3 min of hypercapnia (end‐tidal partial pressure of carbon dioxide +10 mmHg from individual baseline); SNS activity was increased with lower body negative pressure (LBNP; −20 mmHg). CCA and ICA measurements were made using Doppler ultrasound during hypercapnia with (LBNP) or without (Control) SNS activation. LBNP trials began with 5 min of LBNP with subjects breathing hypercapnic gas during the final 3 min. Shear-mediated dilation was calculated as the percent rise in peak diameter from baseline diameter. Sympathetic activation attenuated shear-mediated dilation in the ICA (Control vs. LBNP, 5.5 ± 0.7 vs. 1.8 ± 0.4%, P < 0.01), but not in the CCA (5.1 ± 1.2 vs. 4.2 ± 1.0%, P = 0.31). Moreover, absolute reduction in shear-mediated dilation via SNS activation was greater in the ICA than the CCA (−3.6 ± 0.7 vs. −0.9 ± 0.8%, P = 0.02). Our data indicate that shear-mediated dilation is attenuated during LBNP to a greater extent in the ICA compared with the CCA. These results potentially provide insight into the role of SNS activation on cerebral perfusion, as the ICA is a key supplier of blood to the brain. NEW & NOTEWORTHY We explored the effect of acute sympathetic nervous system (SNS) activation on shear-mediated dilation in the common and internal carotid arteries (CCA and ICA, respectively) in young healthy men. Our data demonstrate that hypercapnia-induced vasodilation of the ICA is attenuated during lower body negative pressure to a greater extent than the CCA. These data may provide novel information related to the role of SNS activation on cerebral perfusion in humans.
Single-Cell Transcriptome Analyses Reveal Endothelial Cell Heterogeneity in Tumors and Changes following Antiangiogenic Treatment
Authors: Zhao Qi , Eichten Alexandra , Parveen Asma , Adler Christina , Huang Ying , Wang Wei , Ding Yueming , Adler Alexander , Nevins Thomas , Ni Min , Wei Yi , Thurston Gavin 
Published: February 2018

Abstract
Angiogenesis involves dynamic interactions between specialized endothelial tip and stalk cells that are believed to be regulated in part by VEGF and Dll4-Notch signaling. However, our understanding of this process is hampered by limited knowledge of the heterogeneity of endothelial cells and the role of different signaling pathways in specifying endothelial phenotypes. Here, we characterized by single-cell transcriptomics the heterogeneity of mouse endothelial cells and other stromal cells during active angiogenesis in xenograft tumors as well as from adult normal heart, following pharmacologic inhibition of VEGF and Dll4-Notch signaling. We classified tumor endothelial cells into three subpopulations that appeared to correspond with tip-like, transition, and stalk-like cells. Previously identified markers for tip and stalk cells were confirmed and several novel ones discovered. Blockade of VEGF rapidly inhibited cell-cycle genes and strongly reduced the proportion of endothelial tip cells in tumors. In contrast, blockade of Dll4 promoted endothelial proliferation as well as tip cell markers; blockade of both pathways inhibited endothelial proliferation but preserved some tip cells. We also phenotypically classified other tumor stromal cells and found that tumor-associated fibroblasts responded to antiangiogenic drug treatments by upregulating hypoxia-associated genes and producing secreted factors involved in angiogenesis. Overall, our findings better define the heterogeneity of tumor endothelial and other stromal cells and reveal the roles of VEGF and Dll4-Notch in specifying tumor endothelial phenotype, highlighting the response of stromal cells to antiangiogenic therapies.
Significance: These findings provide a framework for defining subpopulations of endothelial cells and tumor-associated fibroblasts and their rapid changes in gene expression following antiangiogenic treatment. Cancer Res; 78(9); 2370–82. ©2018 AACR.
Abstract ES10-3: Breast cancer patient-derived xenografts as models for metastatic progression and therapeutic response
Authors: Welm AL 
Published: February 2018

Abstract
Metastasis is the main cause of death from breast cancer, and yet little is understood with regard to how to prevent tumors from appearing in distant organs as metastases, or how to treat them once they appear. Using new models and approaches, we have discovered a new pathway regulating metastasis to lungs and bones. We found that RON kinase regulates breast cancer metastasis through cell-autonomous and non-cell-autonomous mechanisms. This presentation will cover use of various models of breast cancer to study metastasis and therapy response, including patient-derived xenograft (PDX) models. PDX models represent the diversity of human breast tumors, and can be feasibly utilized to test new drugs and drug combinations to find therapeutic approaches that match with molecular features of various tumor types. The goal of our work is to utilize PDX and other relevant in vivo models to obtain preclinical data that will facilitate prioritization of drugs to be tested in breast cancer clinical trials, including RON kinase inhibitors. Taken together, these elements converge to reveal high-priority treatment strategies for future clinical trials in breast cancer patients.
Citation Format: Welm AL. Breast cancer patient-derived xenografts as models for metastatic progression and therapeutic response [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES10-3.
Abstract ES2-1: The pathology of high risk proliferative lesions of the breast
Authors: Siziopikou KP 
Published: February 2018

Abstract
A number of breast lesions diagnosed by pathologic examination of breast tissue are known to confer an increased risk for future development of breast cancer. Atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) are lesions conferring a moderately increased risk of 4-5x over baseline. Lobular carcinoma in situ (LCIS) and variants confer a markedly increased risk of 8-10x over the baseline. The magnitude of the risk, the effect of the patient's age and family history, the laterality of the future malignancy and the type of subsequent cancer development are different between all these high risk proliferative breast lesions. In addition, the spectrum of columnar cell lesions of the breast are thought to represent an early non-obligate precursor in the development of the low grade neoplasia of the breast. Of interest, many of these lesions share common genetic abnormalities that are different than those seen in high grade in situ and invasive carcinomas of the breast. These observations have implications for our current understanding of the breast cancer progression model and our recommendations for the therapeutic management of patients with high risk proliferative lesions of the breast.
Citation Format: Siziopikou KP. The pathology of high risk proliferative lesions of the breast [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES2-1.