bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the pathogenetic association between schizophrenia and type 2 diabetes mellitus diseases based on pathway analysis
Authors: Liu Yanli , Li Zezhi , Zhang Meixia , Deng Youping , Yi Zhenghui , Shi Tieliu 
Published: December 2019

AbstractBackgroundSchizophrenia (SCZ) and type 2 diabetes mellitus (T2D) are both complex diseases. Accumulated studies indicate that schizophrenia patients are prone to present the type 2 diabetes symptoms, but the potential mechanisms behind their association remain unknown. Here we explored the pathogenetic association between SCZ and T2D based on pathway analysis and protein-protein interaction.ResultsWith sets of prioritized susceptibility genes for SCZ and T2D, we identified significant pathways (with adjusted p-value < 0.05) specific for SCZ or T2D and for both diseases based on pathway enrichment analysis. We also constructed a network to explore the crosstalk among those significant pathways. Our results revealed that some pathways are shared by both SCZ and T2D diseases through a number of susceptibility genes. With 382 unique susceptibility proteins for SCZ and T2D, we further built a protein-protein interaction network by extracting their nearest interacting neighbours. Among 2,104 retrieved proteins, 364 of them were found simultaneously interacted with susceptibility proteins of both SCZ and T2D, and proposed as new candidate risk factors for both diseases. Literature mining supported the potential association of partial new candidate proteins with both SCZ and T2D. Moreover, some proteins were hub proteins with high connectivity and interacted with multiple proteins involved in both diseases, implying their pleiotropic effects for the pathogenic association. Some of these hub proteins are the components of our identified enriched pathways, including calcium signaling, g-secretase mediated ErbB4 signaling, adipocytokine signaling, insulin signaling, AKT signaling and type II diabetes mellitus pathways. Through the integration of multiple lines of information, we proposed that those signaling pathways, which contain susceptibility genes for both diseases, could be the key pathways to bridge SCZ and T2D. AKT could be one of the important shared components and may play a pivotal role to link both of the pathogenetic processes.ConclusionsOur study is the first network and pathway-based systematic analysis for SCZ and T2D, and provides the general pathway-based view of pathogenetic association between two diseases. Moreover, we identified a set of candidate genes potentially contributing to the linkage between these two diseases. This research offers new insights into the potential mechanisms underlying the co-occurrence of SCZ and T2D, and thus, could facilitate the inference of novel hypotheses for the co-morbidity of the two diseases. Some etiological factors that exert pleiotropic effects shared by the significant pathways of two diseases may have important implications for the diseases and could be therapeutic intervention targets.
Identification of multiple gene-gene interactions for ordinal phenotypes
Authors: Kim Kyunga , Kwon Min-Seok , Oh Sohee , Park Taesung 
Published: December 2019

Abstract

Background
Multifactor dimensionality reduction (MDR) is a powerful method for analysis of gene-gene interactions and has been successfully applied to many genetic studies of complex diseases. However, the main application of MDR has been limited to binary traits, while traits having ordinal features are commonly observed in many genetic studies (e.g., obesity classification - normal, pre-obese, mild obese and severe obese).

Methods
We propose ordinal MDR (OMDR) to facilitate gene-gene interaction analysis for ordinal traits. As an alternative to balanced accuracy, the use of tau-b, a common ordinal association measure, was suggested to evaluate interactions. Also, we generalized cross-validation consistency (GCVC) to identify multiple best interactions. GCVC can be practically useful for analyzing complex traits, especially in large-scale genetic studies.

Results and conclusions
In simulations, OMDR showed fairly good performance in terms of power, predictability and selection stability and outperformed MDR. For demonstration, we used a real data of body mass index (BMI) and scanned 1~4-way interactions of obesity ordinal and binary traits of BMI via OMDR and MDR, respectively. In real data analysis, more interactions were identified for ordinal trait than binary traits. On average, the commonly identified interactions showed higher predictability for ordinal trait than binary traits. The proposed OMDR and GCVC were implemented in a C/C++ program, executables of which are freely available for Linux, Windows and MacOS upon request for non-commercial research institutions.
Prevalence of diabetes mellitus and impaired glucose tolerance in a rural community of Angola
Authors: Evaristo-Neto Antonio D , Foss-Freitas Maria Cristina , Foss Milton C 
Published: December 2019

Abstract

Background
To determine the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in a rural community (Bengo) of Angola.

Methods
A random sample of 421 subjects aged 30 to 69 years (30% men and 70% women) was selected from three villages of Bengo province. This cross-sectional home survey was conducted using a sampling design of stage conglomerates. First, clinical and anthropometric data were obtained and fasting capillary glucose level was determined. Subjects who screened positive (fasting capillary glucose ≥ 100 mg/dl and < 200 mg/dl) and each sixth consecutive subject who screened negative (fasting capillary glucose < 100 mg/dl) were submitted to the second phase of survey, consisting of the 75-g oral glucose tolerance test. Data was analyzed by the use of SAS statistical software.

Results
The prevalence rates of diabetes mellitus and IGT were 2.8% and 8.1%, respectively. The age group with the highest prevalence of diabetes was 60 to 69 years (42%). Impaired glucose tolerance prevalence was 38% in the 40 to 49 year age group and it increased with age, considering that the 50 to 59 and 60 to 69 year age groups as a whole represent 50% of all subjects with impaired glucose tolerance. The prevalence of diabetes mellitus did not differ significantly between men (3.2%) and women (2.7%) (p = 0.47). On the other hand, the prevalence of impaired glucose tolerance among women showed almost twice that found in men (9.1% vs. 5.6%, respectively). Overweight was present in 66.7% of the individuals with diabetes mellitus and 26.5% of individuals with impaired glucose tolerance showed overweight or obesity.

Conclusions
Although the prevalence of diabetes mellitus was low, the prevalence of impaired glucose tolerance is considered to be within an intermediary range, suggesting a future increase in the frequency of diabetes in this population.
LPS immune challenge reduces arcuate nucleus TSHR and CART mRNA and elevates plasma CART peptides
Authors: Burgos Jonathan R. , Iresjö Britt-Marie , Olsson Linda , Smedh Ulrika 
Published: December 2019

Abstract
Background
The aim was to examine the impact of lipopolysaccharide-induced systemic inflammation on expression of mRNA for cocaine- and amphetamine-regulated transcript (CART) and the thyrotropin receptor (TSHR) and its ligands in CNS areas of relevance for feeding controls and metabolism. Lipopolysaccharide effects on plasma levels of TSH and CART peptides were also examined.

Methods
Lipopolysaccharide (150–200 μg/mouse) was injected in C57BL/6J mice and tissue and plasma samples taken after 24 h. To establish if plasma increase in CART peptide levels were prostanoid dependent, indomethacin was given via the drinking water beginning 48 h prior to LPS. We evaluated mRNA expression for CART, TSHR, TSHβ, and thyrostimulin in brain and pituitary extracts. Plasma levels of TSH, CARTp, and serum amyloid P component were analyzed by ELISA.

Results
Lipopolysaccharide suppressed TSHR mRNA expression in the arcuate nucleus and the pituitary. CART mRNA expression was reduced in the arcuate nucleus but elevated in the pituitary of mice treated with Lipopolysaccharide, whereas plasma TSH remained unchanged. Plasma CART peptide concentration increased after LPS treatment in a prostanoid-independent manner, and CART peptide levels correlated positively to degree of inflammation.

Conclusions
Our findings suggest that central and peripheral CART is affected by acute inflammation. Considering the role of the arcuate nucleus in feeding controls, our data highlight TSHR and CART as putative neuroendocrine signaling components that respond to inflammation, perhaps to maintain weight and metabolic homeostasis during states of disease.
Strategies for recruitment in general practice settings: the iSOLVE fall prevention pragmatic cluster randomised controlled trial
Authors: Tan Amy C. W. , Clemson Lindy , Mackenzie Lynette , Sherrington Catherine , Roberts Chris , Tiedemann Anne , Pond Constance D. , White Fiona , Simpson Judy M. 
Published: December 2019

Abstract
Background
Falls are common among older people, and General Practitioners (GPs) could play an important role in implementing strategies to manage fall risk. Despite this, fall prevention is not a routine activity in general practice settings. The iSOLVE cluster randomised controlled trial aimed to evaluate implementation of a fall prevention decision tool in general practice. This paper sought to describe the strategies used and reflect on the enablers and barriers relevant to successful recruitment of general practices, GPs and their patients.

Methods
Recruitment was conducted within the geographical area of a Primary Health Network in Northern Sydney, Australia. General practices and GPs were engaged via online surveys, mailed invitations to participate, educational workshops, practitioner networks and promotional practice visits. Patients 65 years or older were recruited via mailed invitations, incorporating the practice letterhead and the name(s) of participating GP(s). Observations of recruitment strategies, results and enabling factors were recorded in field notes as descriptive and narrative data, and analysed using mixed-methods.

Results
It took 19 months to complete recruitment of 27 general practices, 75 GPs and 560 patients. The multiple strategies used to engage general practices and GPs were collectively useful in reaching the targeted sample size. Practice visits were valuable in engaging GPs and staff, establishing interest in fall prevention and commitment to the trial. A mix of small, medium and large practices were recruited. While some were recruited as a whole-practice, other practices had few or half of the number of GPs recruited. The importance of preventing falls in older patients, simplicity of research design, provision of resources and logistic facilitation of patient recruitment appealed to GPs. Recruitment of older patients was successfully achieved by mailed invitations which was a strategy that was familiar to practice staff and patients. Patient response rates were above the expected 10% for most practices. Many practices (n = 17) achieved the targeted number of 20 or more patients.

Conclusions
Recruitment in general practice settings can be successfully achieved through multiple recruitment strategies, effective communication and rapport building, ensuring research topic and design suit general practice needs, and using familiar communication strategies to engage patients.

Trial registration
The trial was prospectively registered on 29 April 2015 with the Australian New Zealand Clinical Trial Registry www.anzctr.org.au (trial ID: ACTRN12615000401550).
Process evaluation of the community-based newborn care program implementation in Geze Gofa district, south Ethiopia: a case study evaluation design
Authors: Gebremedhin Tsegaye , Daka Dawit Wolde , Alemayehu Yibeltal Kiflie , Yitbarek Kiddus , Debie Ayal 
Published: December 2019

Abstract
Background
The Community-Based Newborn Care (CBNC) program is a comprehensive strategy designed to improve the health of newborns during pregnancy, childbirth, and the postnatal period through health extension workers at community levels, although the implementation has not been evaluated yet. Therefore, this study aimed to evaluate the process of the CBNC program implementation in Geze Gofa district, south Ethiopia.

Methods
A case study evaluation design with a mixed method was employed from May 1 to 31, 2017. A total of 321 mothers who gave birth from September 01, 2016 to February 29, 2017, were interviewed. Similarly, 27 direct observations, six-month document reviews, and 14 key informant interviews were conducted. The quantitative data were entered into Epi-Data version 3.1 and exported to SPSS version 20 for analysis. In the multivariable logistic regression analysis, variables with < 0.05 p-values and Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) were used to declare factors associated with maternal satisfaction. The qualitative data were transcribed, translated, coded, and analyzed using thematic analysis. The overall process of program implementation was measured based on pre-determined judgmental criteria.

Results
The overall level of the implementation process of the CBNC program was 72.7%, to which maternal satisfaction, availability of resources, and healthcare providers’ compliance with the national guideline contributed 75.0, 81.0, and 68.0%, respectively. Essential drugs and medical equipment, like vitamin K, chlorohexidine ointment, neonatal resuscitation bags, and masks used in the program were out of stock. Very severe diseases were not treated according to the national guidelines, and the identification of neonatal sepsis cases was poor. Trading occupation (AOR: 0.16, 95% CI: 0.03–0.97) and low wealth status (AOR: 3.11, 95% CI: 1.16–8.36) were factors associated with maternal satisfaction.

Conclusion
The process of CBNC program implementation was relatively good, although the compliance of healthcare providers with the national guideline and maternal satisfaction with the services was low. Some essential drugs and medical equipment were out of stock. Merchant and low wealth status affected maternal satisfaction. Therefore, healthcare offices should provide crucial medicines and equipment for better program implementation and improve the wealth status of mothers to enhance maternal satisfaction.
Assessment of precision irradiation in early non-small cell lung cancer and interstitial lung disease (ASPIRE-ILD): study protocol for a phase II trial
Authors: Palma David A. , Chen Hanbo , Bahig Houda , Gaede Stewart , Harrow Stephen , Laba Joanna M. , Qu X. Melody , Rodrigues George B. , Yaremko Brian P. , Yu Edward , Louie Alexander V. , Dhaliwal Inderdeep , Ryerson Christopher J. 
Published: December 2019

Abstract
Background
Stereotactic ablative radiotherapy (SABR) has become an established treatment option for medically-inoperable early-stage (Stage I-IIA) non-small cell lung cancer (ES-NSCLC). SABR is able to obtain high rates of local control with low rates of symptomatic toxicity in this patient population. However, in a subset of patients with fibrotic interstitial lung disease (ILD), elevated rates of SABR-related toxicity and mortality have been described. The Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD) study will conduct a thorough prospective evaluation of the clinical outcomes, toxicity, changes in diagnostic test parameters and patient-related outcomes following SABR for ES-NSCLC for patients with fibrotic ILD.

Methods
ASPIRE-ILD is a single-arm Phase II prospective study. The accrual target is 39 adult patients with T1–2N0M0 non-small cell lung cancer with co-existing ILD who are not candidates for surgical excision. Pathological confirmation of diagnosis is strongly recommended but not strictly required. Enrolled patients will be stratified by ILD-related mortality risk. The starting SABR dose will be 50 Gy in 5 fractions every other day (biologically effective dose: 100 Gy10 or 217 Gy3), but the radiation dose can be de-escalated up to two times to 50 Gy in 10 fractions daily (75 Gy10 or 133 Gy3) and 45 Gy in 15 fractions daily (58 Gy10 or 90 Gy3). Dose de-escalation will occur if 2 or more of the first 7 patients in a cohort experiences grade 5 toxicity within 6 months of treatment. Similarly, dose de-escalation can also occur if 2 or more of the first 7 patients with a specific subtype of ILD experiences grade 5 toxicity within 6 months of treatment. The primary endpoint is overall survival. Secondary endpoints include toxicity (CTC-AE 4.0), progression-free survival, local control, patient-reported outcomes (cough severity and quality of life), rates of ILD exacerbation and changes in pulmonary function tests/high-resolution computed tomography findings post-SABR.

Discussion
ASPIRE-ILD will be the first prospective study specifically designed to comprehensively evaluate the effectiveness and safety of SABR for ES-NSCLC in patients with co-existing ILD.

Trial registration
Clinicaltrials.gov identifier: NCT03485378. Date of registration: April 2, 2018.
Who is afraid of ticks and tick-borne diseases? Results from a cross-sectional survey in Scandinavia
Authors: Slunge Daniel , Jore Solveig , Krogfelt Karen Angeliki , Jepsen Martin Tugwell , Boman Anders 
Published: December 2019

Abstract
Background
In Scandinavia, the distribution of ticks is expanding and tick-borne diseases constitute growing health risks. While the probability of getting a tick-borne disease after a tick bite is low, the health impacts can be large. This, as well as other characteristics of these diseases make tick-related risks difficult for laypeople to assess and perceived risk may differ substantially from actual risk. Understanding risk perceptions is important since it is the perceived risk, rather than actual risk, that determine behaviour and even more so for new and emerging risks. The aim of this study is to investigate knowledge and risk perceptions related to tick bites and the tick-borne diseases Lyme borreliosis (LB) and tick-borne encephalitis (TBE). By analysing risk perceptions and knowledge, the study helps inform the development of public health strategies in response to the increasing incidence of these diseases in Scandinavia.

Methods
Two thousand, six hundred sixty-eight respondents in Denmark, Norway and Sweden answered an online questionnaire with 48 questions, including 7 questions on risk perceptions and 9 knowledge questions. Chi-squared tests were used to analyse statistical differences between country sub-samples, gender and age groups. A multivariate regression model was used to analyse factors associated with risk perceptions.

Results
Risk perceptions were on average high in comparison with scientific estimates, with respondents grossly overrating the probability of contracting LB or TBE if bitten by a tick. Also, the average perceived seriousness of a single tick bite and of getting LB or TBE was high. Knowledge on the other hand was low, especially among men and the youngest age group (18–29 years). Higher levels of knowledge about tick-borne diseases were associated with lower perceived seriousness of tick bites and LB and higher perceived seriousness of TBE. Also, having been diagnosed with LB was negatively associated with the perceived seriousness of LB.

Conclusions
Our results indicate that informing about ticks and tick-borne diseases would be a relevant public health strategy as it could make risk perceptions better aligned with actual risk.
Should the TBE virus spread further in Denmark and Norway, increasing knowledge about TBE vaccination would be especially important.
Under-reporting of TB cases and associated factors: a case study in China
Authors: Zhou Danju , Pender Michelle , Jiang Weixi , Mao Wenhui , Tang Shenglan 
Published: December 2019

Abstract
Background
Tuberculosis is a leading cause of death worldwide and has become a high global health priority. Accurate country level surveillance is critical to ending the pandemic. Effective routine reporting systems which track the course of the epidemic are vital in addressing TB. China, which has the third largest TB epidemic in the world and has developed a reporting system to help with the control and prevention of TB, this study examined its effectiveness in Eastern China.

Methods
The number of TB cases reported internally in two hospitals in Eastern China were compared to the number TB cases reported by these same hospitals in the national reporting systems in order to assess the accuracy of reporting. Qualitative data from interviews with key health officials and researcher experience using the TB reporting systems were used to identify factors affecting the accuracy of TB cases being reported in the national systems.

Results
This study found that over a quarter of TB cases recorded in the internal hospital records were not entered into the national TB reporting systems, leading to an under representation of national TB cases. Factors associated with underreporting included unqualified and overworked health personnel, poor supervision and accountability at local and national levels, and a complicated incohesive health information management system.

Conclusions
This study demonstrates that TB in Eastern China is being underreported. Given that Eastern China is a developed province, one could assume similar problems may be found in other parts of China with fewer resources as well as many low- and middle-income countries. Having an accurate account of the number of national TB cases is essential to understanding the national and global burden of the disease and in managing TB prevention and control efforts. As such, factors associated with underreporting need to be addressed in order to reduce underreporting.