bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal galactosylation of immunoglobulin G in cerebrospinal fluid of multiple sclerosis patients
Authors: Decker Yann , Schomburg Robert , Németh Eszter , Vitkin Artem , Fousse Mathias , Liu Yang , Fassbender Klaus 
Published: February 2016

Background: Glycosylation alterations have been associated with the development of several human diseases and their animal models, including multiple sclerosis. Objectives: We aimed to determine whether immunoglobulin G galactosylation might be changed in multiple sclerosis. Methods: Immunoglobulin G was isolated from serum and cerebrospinal fluid of patients with multiple sclerosis or viral meningitis and control patients without history of inflammatory or autoimmune disease. A lectin-based assay was used to investigate potential galactosylation modifications of immunoglobulin G. Results and conclusion: Galactosylation of immunoglobulin G isolated from cerebrospinal fluid of control patients was found to be age- and gender-dependent. In addition, immunoglobulin G galactosylation was significantly altered in cerebrospinal fluid but not in serum of multiple sclerosis patients. Furthermore, this modification was correlated with an active progression of multiple sclerosis. Finally, the loss of galactosyl moieties was not simply associated with inflammation as no such change was detected in viral meningitis patients characterized by brain inflammation.
A randomised, controlled trial of the effects of a mobile telehealth intervention on clinical and patient-reported outcomes in people with poorly controlled diabetes
Authors: Baron Justine S , Hirani Shashivadan , Newman Stanton P 
Published: February 2016

Objective The objective of this research is to determine the effects of mobile telehealth (MTH) on glycosylated haemoglobin (HbA1c) and other clinical and patient-reported outcomes in insulin-requiring people with diabetes. Methods A nine-month randomised, controlled trial compared standard care to standard care supplemented with MTH (self-monitoring, mobile-phone data transmissions, graphical and nurse-initiated feedback, and educational calls). Clinical (HbA1c, blood pressure, daily insulin dose, diabetes outpatient appointments (DOAs)) and questionnaire data (health-related quality of life, depression, anxiety) were collected. Mean group changes over time were compared using hierarchical linear models and Mann-Whitney tests. Results Eighty-one participants with a baseline HbA1c of 8.98% ± 1.82 were randomised to the intervention ( n = 45) and standard care ( n = 36). The Group by Time effect revealed MTH did not significantly influence HbA1c ( p = 0.228), but p values were borderline significant for blood pressure ( p = 0.054) and mental-health related quality of life ( p = 0.057). Examination of effect sizes and 95% confidence intervals for mean group differences at nine months supported the existence of a protective effect of MTH on mental health-related quality of life as well as depression. None of the other measured outcomes were found to be affected by the MTH intervention. Conclusions Findings from this study must be interpreted with caution given the small sample size, but they do not support the widespread adoption of MTH to achieve clinically significant changes in HbA1c. MTH may, however, have positive effects on blood pressure and protective effects on some aspects of mental health.
Patient compliance with postoperative analgesia after day case surgery: a multisite observational study of patients in North East London
Authors: Fahmy Nisreen , Siah Julian , Umo-Etuk Joanna 
Published: February 2016

Background: Pain is the commonest reason for delayed discharge and readmission post day surgery with up to 45% of patients reported to suffer moderate-to-severe post-surgical pain 24 hours after discharge. The importance of post-surgical pain management extends beyond the acute phase when one considers that all chronic post-surgical pain was once acute. Although much focus is given to perioperative analgesia, a patient’s pain management once discharged can be overlooked, whilst at this time the patient’s pain management is within their own hands. Methods: We conducted this multisite observational study of adult patients undergoing day case surgery. After obtaining patient consent data was collected on the operation, intra- and postoperative analgesia administered and discharge analgesia prescribed. Patients were then contacted at home by telephone 48 hours after discharge and asked about their postoperative pain and analgesia requirements. Results: Of 150 patients consented for the enrolment, we were able to obtain postoperative analgesia data on 100. A total of 68% of patients reported pain following discharge with 26% reporting severe pain, defined as a pain score of ⩾7. A total 68% of patients were prescribed and dispensed analgesia, and of those, 83% were compliant with their analgesia. Thus, we conclude that in this patient group, the incidence of postoperative pain was not due to lack of patient compliance, but inadequate analgesia prescription. Discussion: We recognise that our data reflect a patient population in North East London but suggest that the results may still be relevant to a wider patient group across the United Kingdom as the incidence of postoperative pain in our study was similar to published figures. Better patient satisfaction with postoperative analgesia may be obtained with more patient- and surgery-specific analgesic prescription.
Oxytocin improves cytological and histological profiles of vaginal atrophy in postmenopausal women
Authors: Al-Saqi Shahla Hamza , Jonasson Aino Fianu , Naessén Tord , Uvnäs-Moberg Kerstin 
Published: February 2016

Objective To investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological and histological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo. Study design Sixty-eight postmenopausal women diagnosed with vaginal atrophy were randomized for this multicenter, double-blinded, placebo-controlled trial. Thirty-three women received 600 IU vagitocin, an oxytocin containing gel, and 35 women received a placebo gel intravaginally. The dose was 600 IU daily for the first two weeks and thereafter 600 IU twice a week for 10 weeks. All participant women underwent four visits and a subgroup of 20 women had a further fifth visit. Vaginal smears for cytological evaluation were collected at all visits. Vaginal biopsies were taken in 20 women before and after 12 weeks of treatment for histological analysis. In these women a vaginal smear was also collected after 14 weeks. Results The increase in the percentage of superficial cells between 0 and 2 weeks was significantly greater after treatment with vagitocin in comparison with placebo (p = 0.04). The difference in the maturation value between 0 and 12 weeks was significantly higher in the vagitocin than in the placebo group (p = 0.01). The reduction in the scores of atrophy was according to the histological investigation significantly greater in the vagitocin group than in the placebo group at 12 weeks (p < 0.04). Conclusion Daily intravaginal treatment with vagitocin 600 IU improves expressions of vaginal atrophy as recorded by cytological investigation of vaginal smears and histological analysis of vaginal biopsies. Treatment twice weekly seems to be less effective regarding the increase in superficial cells.
CellECT: cell evolution capturing tool
Authors: Delibaltov Diana L. , Gaur Utkarsh , Kim Jennifer , Kourakis Matthew , Newman-Smith Erin , Smith William , Belteton Samuel A. , Szymanski Daniel B. , Manjunath B. S. 
Published: February 2016

Abstract
Background
Robust methods for the segmentation and analysis of cells in 3D time sequences (3D+t) are critical for quantitative cell biology. While many automated methods for segmentation perform very well, few generalize reliably to diverse datasets. Such automated methods could significantly benefit from at least minimal user guidance. Identification and correction of segmentation errors in time-series data is of prime importance for proper validation of the subsequent analysis. The primary contribution of this work is a novel method for interactive segmentation and analysis of microscopy data, which learns from and guides user interactions to improve overall segmentation.

Results
We introduce an interactive cell analysis application, called CellECT, for 3D+t microscopy datasets. The core segmentation tool is watershed-based and allows the user to add, remove or modify existing segments by means of manipulating guidance markers. A confidence metric learns from the user interaction and highlights regions of uncertainty in the segmentation for the user’s attention. User corrected segmentations are then propagated to neighboring time points. The analysis tool computes local and global statistics for various cell measurements over the time sequence. Detailed results on two large datasets containing membrane and nuclei data are presented: a 3D+t confocal microscopy dataset of the ascidian Phallusia mammillata consisting of 18 time points, and a 3D+t single plane illumination microscopy (SPIM) dataset consisting of 192 time points. Additionally, CellECT was used to segment a large population of jigsaw-puzzle shaped epidermal cells from Arabidopsis thaliana leaves. The cell coordinates obtained using CellECT are compared to those of manually segmented cells.

Conclusions
CellECT provides tools for convenient segmentation and analysis of 3D+t membrane datasets by incorporating human interaction into automated algorithms. Users can modify segmentation results through the help of guidance markers, and an adaptive confidence metric highlights problematic regions. Segmentations can be propagated to multiple time points, and once a segmentation is available for a time sequence cells can be analyzed to observe trends. The segmentation and analysis tools presented here generalize well to membrane or cell wall volumetric time series datasets.
Common fixed point results of a pair of generalized $(\psi,\varphi )$-contraction mappings in modular spaces
Authors: Öztürk Mahpeyker , Abbas Mujahid , Girgin Ekber 
Published: February 2016

AbstractIn this paper, we establish the existence of a common fixed point of almost generalized contractions on modular spaces. As an application, we present some fixed and common fixed point results for such mappings on modular spaces endowed with a graph. The existence of fixed and common points of mappings satisfying generalized contractive conditions of integral type is also obtained in such spaces. Some examples are presented to support the results obtained herein. Our results generalize and extend various comparable results in the existing literature.
Low birth weight and features of neuroticism and mood disorder
in 83 545 participants of the UK Biobank cohort
Authors: Lyall Donald M. , Inskip Hazel M. , Mackay Daniel , Deary Ian J. , McIntosh Andrew M. , Hotopf Matthew , Kendrick Tony , Pell Jill P. , Smith Daniel J. 
Published: February 2016

BackgroundLow birth weight has been inconsistently associated with risk of
developing affective disorders, including major depressive disorder
(MDD). To date, studies investigating possible associations between birth
weight and bipolar disorder (BD), or personality traits known to
predispose to affective disorders such as neuroticism, have not been
conducted in large cohorts.AimsTo assess whether very low birth weight (<1500 g) and low birth weight
(1500–2490 g) were associated with higher neuroticism scores assessed in
middle age, and lifetime history of either MDD or BD. We controlled for
possible confounding factors.MethodRetrospective cohort study using baseline data on the 83 545 UK Biobank
participants with detailed mental health and birth weight data. Main
outcomes were prevalent MDD and BD, and neuroticism assessed using the
Eysenck Personality Inventory Neuroticism scale - Revised (EPIN-R)ResultsReferent to normal birth weight, very low/low birth weight were
associated with higher neuroticism scores, increased MDD and BD. The
associations between birth weight category and MDD were partially
mediated by higher neuroticism.ConclusionsThese findings suggest that intrauterine programming may play a role in
lifetime vulnerability to affective disorders.
Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study
Authors: Goebeler Maria-Elisabeth , Knop Stefan , Viardot Andreas , Kufer Peter , Topp Max S. , Einsele Hermann , Noppeney Richard , Hess Georg , Kallert Stefan , Mackensen Andreas , Rupertus Kathrin , Kanz Lothar , Libicher Martin , Nagorsen Dirk , Zugmaier Gerhard , Klinger Matthias , Wolf Andreas , Dorsch Brigitte , Quednau Beate D. , Schmidt Margit , Scheele Jürgen , Baeuerle Patrick A. , Leo Eugen , Bargou Ralf C. 
Published: February 2016

PurposeBlinatumomab is a CD19/CD3 BiTE (bispecific T-cell engager) antibody construct for the treatment of Philadelphia chromosome–negative acute B-lymphoblastic leukemia. We evaluated blinatumomab in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).Patients and MethodsThis 3 + 3 design, phase I dose-escalation study determined adverse events and the maximum tolerated dose (MTD) of continuous intravenous infusion blinatumomab in patients with relapsed/refractory NHL. Blinatumomab was administered over 4 or 8 weeks at seven different dose levels (0.5 to 90 μg/m2/day). End points were incidence of adverse events, pharmacokinetics, pharmacodynamics, and overall response rate.ResultsBetween 2004 and 2011, 76 heavily pretreated patients with relapsed/refractory NHL, who included 14 with diffuse large B-cell lymphoma, were enrolled; 42 received treatment in the formal dose-escalation phase. Neurologic events were dose limiting, and 60 μg/m2/day was established as the MTD. Thirty-four additional patients were recruited to evaluate antilymphoma activity and strategies for mitigating neurologic events at a prespecified MTD. Stepwise dosing (5 to 60 μg/m2/day) plus pentosan polysulfate SP54 (n = 3) resulted in no treatment discontinuations; single-step (n = 5) and double-step (n = 24) dosing entailed two and seven treatment discontinuations due to neurologic events, respectively. Grade 3 neurologic events occurred in 22% of patients (no grade 4/5). Among patients treated at 60 μg/m2/day (target dose; n = 35), the overall response rate was 69% across NHL subtypes and 55% for diffuse large B-cell lymphoma (n = 11); median response duration was 404 days (95% CI, 207 to 1,129 days).ConclusionIn this phase I study of relapsed/refractory NHL, continuous infusion with CD19-targeted immunotherapy blinatumomab at various doses and schedules was feasible, with an MTD of 60 μg/m2/day. Single-agent blinatumomab showed antilymphoma activity.
Increased Risk for Other Cancers in Addition to Breast Cancer for CHEK2*1100delC Heterozygotes Estimated From the Copenhagen General Population Study
Authors: Näslund-Koch Charlotte , Nordestgaard Børge G. , Bojesen Stig E. 
Published: February 2016

Purpose CHEK2 is a cell cycle checkpoint regulator, and the CHEK2*1100delC germline mutation leads to loss of function and increased breast cancer risk. It seems plausible that this mutation could also predispose to other cancers. Therefore, we tested the hypothesis that CHEK2*1100delC heterozygosity is associated with increased risk for other cancers in addition to breast cancer in the general population. Patients and Methods We examined 86,975 individuals from the Copenhagen General Population Study, recruited from 2003 through 2010. The participants completed a questionnaire on health and lifestyle, were examined physically, had blood drawn for DNA extraction, were tested for presence of CHEK2*1100delC using Taqman assays and sequencing, and were linked over 1943 through 2011 to the Danish Cancer Registry. Incidences and risks of individual cancer types, including breast cancer, were calculated using Kaplan-Meier estimates, Fine and Gray competing-risks regressions, and stratified analyses with interaction tests. Results Among 86,975 individuals, 670 (0.8%) were CHEK2*1100delC heterozygous, 2,442 developed breast cancer, and 6,635 developed other cancers. The age- and sex-adjusted hazard ratio for CHEK2*1100delC heterozygotes compared with noncarriers was 2.08 (95% CI, 1.51 to 2.85) for breast cancer and 1.45 (95% CI, 1.15 to 1.82) for other cancers. When stratifying for sex, the age-adjusted hazard ratios for other cancers were 1.54 (95% CI, 1.08 to 2.18) for women and 1.37 (95% CI, 1.01 to 1.85) for men (sex difference: P = .63). For CHEK2*1100delC heterozygotes compared with noncarriers, the age- and sex-adjusted hazard ratios were 5.76 (95% CI, 2.12 to 15.6) for stomach cancer, 3.61 (95% CI, 1.33 to 9.79) for kidney cancer, 3.45 (95% CI, 1.09 to 10.9) for sarcoma, and 1.60 (95% CI, 1.00 to 2.56) for prostate cancer. Conclusion CHEK2*1100delC heterozygosity is associated with 15% to 82% increased risk for at least some cancers in addition to breast cancer. This information may be useful in clinical counseling of patients with this loss-of-function mutation.
Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction
Authors: Li Jin , Qin Shukui , Xu Jianming , Xiong Jianping , Wu Changping , Bai Yuxian , Liu Wei , Tong Jiandong , Liu Yunpeng , Xu Ruihua , Wang Zhehai , Wang Qiong , Ouyang Xuenong , Yang Yan , Ba Yi , Liang Jun , Lin Xiaoyan , Luo Deyun , Zheng Rongsheng , Wang Xin , Sun Guoping , Wang Liwei , Zheng Leizhen , Guo Hong , Wu Jingbo , Xu Nong , Yang Jianwei , Zhang Honggang , Cheng Ying , Wang Ningju , Chen Lei , Fan Zhining , Sun Piaoyang , Yu Hao 
Published: February 2016

Purpose There is currently no standard treatment strategy for patients with advanced metastatic gastric cancer experiencing progression after two or more lines of chemotherapy. We assessed the efficacy and safety of apatinib, a novel vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, in patients with advanced gastric or gastroesophageal junction adenocarcinoma for whom at least two lines of prior chemotherapy had failed. Patients and Methods This was a randomized, double-blind, placebo-controlled phase III trial. Patients from 32 centers in China with advanced gastric or gastroesophageal junction adenocarcinoma, for whom two or more prior lines of chemotherapy had failed, were enrolled. Patients were randomly assigned to oral apatinib 850 mg or placebo once daily. The primary end points were overall (OS) and progression-free survival (PFS). Results Between January 2011 and November 2012, 267 patients were enrolled. Median OS was significantly improved in the apatinib group compared with the placebo group (6.5 months; 95% CI, 4.8 to 7.6 v 4.7 months; 95% CI, 3.6 to 5.4; P = .0149; hazard ratio, 0.709; 95% CI, 0.537 to 0.937; P = .0156). Similarly, apatinib significantly prolonged median PFS compared with placebo (2.6 months; 95% CI, 2.0 to 2.9 v 1.8 months; 95% CI, 1.4 to 1.9; P < .001; hazard ratio, 0.444; 95% CI, 0.331 to 0.595; P < .001). The most common grade 3 to 4 nonhematologic adverse events were hand-foot syndrome, proteinuria, and hypertension. Conclusion These data show that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy.
Proposed Staging System for Patients With HPV-Related Oropharyngeal Cancer Based on Nasopharyngeal Cancer N Categories
Authors: Dahlstrom Kristina R. , Garden Adam S. , William William N. , Lim Ming Yann , Sturgis Erich M. 
Published: February 2016

Purpose Patients with human papillomavirus (HPV)–related oropharyngeal cancer (OPC) generally present with more advanced disease but have better survival than patients with HPV-unrelated OPC. The current American Joint Commission on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system for OPC was developed for HPV-unrelated OPC. A new staging system is needed to adequately predict outcomes of patients with HPV-related OPC. Patients and Methods Patients with newly diagnosed HPV-positive OPC (by p16 immunohistochemistry or in situ hybridization) treated at our institution from January 2003 through December 2012 were included. By using recursive partitioning analysis (RPA), we developed new stage groupings with both traditional OPC regional lymph node (N) categories and nasopharyngeal carcinoma (NPC) N categories. Survival was estimated by the Kaplan-Meier method, and the relationship between stage and survival was examined by using Cox proportional hazards regression analysis. Results A total of 661 patients with HPV-positive OPC met the inclusion criteria. With the traditional TNM staging system, there was no difference in survival between stages (P = .141). RPA with NPC N categories resulted in more balanced stage groups and better separation between groups for 5-year survival than RPA with traditional OPC N categories. With the stage groupings that were based in part on NPC N categories, the risk of death increased with increasing stage (P for trend < .001), and patients with stage III disease had five times the risk of death versus patients with stage IA disease. Conclusion New stage groupings that are based on primary tumor (T) categories and NPC N categories better separate patients with HPV-positive OPC with respect to survival than does the current AJCC/UICC TNM staging system. Although confirmation of our findings in other patient populations is needed, we propose consideration of NPC N categories as an alternative to the traditional OPC N categories in the new AJCC/UICC TNM staging system that is currently being developed.
Improved Method to Stratify Elderly Patients With Cancer at Risk for Competing Events
Authors: Carmona Ruben , Zakeri Kaveh , Green Garrett , Hwang Lindsay , Gulaya Sachin , Xu Beibei , Verma Rohan , Williamson Casey W. , Triplett Daniel P. , Rose Brent S. , Shen Hanjie , Vaida Florin , Murphy James D. , Mell Loren K. 
Published: February 2016

PurposeTo compare a novel generalized competing event (GCE) model versus the standard Cox proportional hazards regression model for stratifying elderly patients with cancer who are at risk for competing events.MethodsWe identified 84,319 patients with nonmetastatic prostate, head and neck, and breast cancers from the SEER-Medicare database. Using demographic, tumor, and clinical characteristics, we trained risk scores on the basis of GCE versus Cox models for cancer-specific mortality and all-cause mortality. In test sets, we examined the predictive ability of the risk scores on the different causes of death, including second cancer mortality, noncancer mortality, and cause-specific mortality, using Fine-Gray regression and area under the curve. We compared how well models stratified subpopulations according to the ratio of the cumulative cause-specific hazard for cancer mortality to the cumulative hazard for overall mortality (ω) using the Akaike Information Criterion.ResultsIn each sample, increasing GCE risk scores were associated with increased cancer-specific mortality and decreased competing mortality, whereas risk scores from Cox models were associated with both increased cancer-specific mortality and competing mortality. GCE models created greater separation in the area under the curve for cancer-specific mortality versus noncancer mortality (P < .001), indicating better discriminatory ability between these events. Comparing the GCE model to Cox models of cause-specific mortality or all-cause mortality, the respective Akaike Information Criterion scores were superior (lower) in each sample: prostate cancer, 28.6 versus 35.5 versus 39.4; head and neck cancer, 21.1 versus 29.4 versus 40.2; and breast cancer, 24.6 versus 32.3 versus 50.8.ConclusionCompared with standard modeling approaches, GCE models improve stratification of elderly patients with cancer according to their risk of dying from cancer relative to overall mortality.