bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrated intervention for chronic care management in rural Nepal: a protocol of a type 2 hybrid effectiveness-implementation study
Authors: Schwarz Dan , Dhungana Santosh , Kumar Anirudh , Acharya Bibhav , Agrawal Pawan , Aryal Anu , Baum Aaron , Choudhury Nandini , Citrin David , Dangal Binod , Dhimal Meghnath , Gauchan Bikash , Gupta Tula , Halliday Scott , Karmacharya Biraj , Kishore Sandeep , Koirala Bhagawan , Kshatriya Uday , Levine Erica , Maru Sheela , Rimal Pragya , Sapkota Sabitri , Schwarz Ryan , Shrestha Archana , Thapa Aradhana , Maru Duncan 
Published: January 2020

Abstract
Background In Nepal, the burden of non-communicable, chronic diseases is rapidly rising, and disproportionately affecting low- and middle-income countries. Integrated interventions are essential in strengthening primary care systems and addressing the burden of multiple comorbidities. A growing body of literature supports the involvement of frontline providers, namely mid-level practitioners and community health workers, in chronic care management. Important operational questions remain, however, around the digital, training, and supervisory structures to support the implementation of effective, affordable, and equitable chronic care management programs. Methods A twelve-month, population-level, type 2 hybrid effectiveness-implementation study will be conducted in rural Nepal to evaluate an integrated non-communicable disease care management intervention within Nepal’s new municipal governance structure. The intervention will leverage the government’s planned roll-out of the World Health Organization’s Package of Essential Non-communicable disease interventions (WHO-PEN) program in four municipalities in Nepal, with a study population of 80,000. The intervention will leverage both the WHO-PEN and its cardiovascular disease specific technical guidelines, HEARTS, and include three evidence-based components: 1) non-communicable disease care provision using mid-level practitioners and community health workers; 2) digital clinical decision support tools to ensure delivery of evidence-based care; and 3) training and digitally-supported supervision of mid-level practitioners to provide motivational interviewing for modifiable risk factor optimization, with a focus on medication adherence, and tobacco and alcohol use. The study will evaluate effectiveness using a pre-post design with stepped implementation. The primary outcomes will be disease-specific, “at-goal” metrics of chronic care management; secondary outcomes will include alcohol and tobacco consumption levels. Discussion This is the first population-level, hybrid effectiveness-implementation study of an integrated chronic care management intervention in Nepal. As low- and middle-income countries plan for the Sustainable Development Goals and universal health coverage, the results of this pragmatic study will offer insights into policy and programmatic design for non-communicable disease care management in the future.
M1 Macrophage Infiltrations Exacerbate Muscle and Bone Atrophy after Peripheral Nerve Injury
Authors: Shimada Nobuhiro , Sakata Asuka , Igarashi Takashi , Takeuchi Mamoru , Nishimura Satoshi 
Published: January 2020

Abstract
Background: Peripheral nerve injury causes limb muscle/bone atrophy, leading to chronic pain. However, the mechanisms underlying muscle/bone atrophy after peripheral nerve injury remain unknown. It was recently reported that M1 macrophages are the main factors responsible for neurogenic inflammation after peripheral nerve injury. We hypothesized that M1 macrophages are important in muscle/bone atrophy after nerve injury. Therefore, we investigated the influence of M1 macrophages on muscle/bone atrophy after nerve injury in mice to prevent muscle/bone atrophy by suppressing M1 macrophages.

Methods: Hindlimb muscle weight and total bone density were measured in a chronic constriction injury (CCI) mouse model. Immunohistochemical analysis and intravital microscopy were performed to visualize hindlimb muscles/bones, and cells were quantified using flow cytometry. We compared M1 macrophage infiltration into muscles/bones and muscle/bone atrophy between macrophage depletion and untreated groups. We also investigated muscle/bone atrophy using administration models for anti-inflammatory and neuropathic pain drugs.

Results: Peripheral nerve injury caused significant reduction in muscle weight and total bone density at 1 and 3 weeks after CCI, respectively, compared with that in controls. Osteoclast numbers were significantly higher at 1 week after CCI in the CCI group than in the control group. M1 macrophage infiltration into muscles was observed from 2 hours after CCI via intravital microscopy and 1 week after CCI, and it was significantly higher 1 week after CCI than in the control group. In the macrophage depletion group, dexamethasone, pregabalin, and loxoprofen groups, M1 macrophage infiltration into muscles/bones was significantly lower and muscle weight and total bone density were significantly higher than in the untreated group.

Conclusions: M1 macrophage infiltration exacerbates muscle/bone atrophy after peripheral nerve injury. By suppressing M1 macrophages at the neural injury local site, muscle/bone atrophy could be avoided.
A Randomized Double-Blind Comparison of the Double-Space Technique versus the Single-Space Technique in Combined Spinal-Epidural Anesthesia for Cesarean Section
Authors: Chun Eun Hee , Cho Sooyoung , Woo Jae Hee , Kim Youn Jin 
Published: January 2020

Abstract
Background: Combined spinal-epidural anesthesia (CSEA) can be performed with either a single-space technique or a double-space technique for cesarean section. We performed a double-blind randomized controlled study to compare the effect of the double-space technique with that of the single-space technique on sensory block level and side effects.

Methods: Parturients undergoing elective cesarean section under regional anesthesia were randomized to receive CSEA with either the double-space technique (double group, n = 20) or the single-space technique (single group, n = 20). In the double group, an epidural catheter was inserted at the L1–2 interspace, and dural puncture was performed at the L3–4 interspace. In the single group, the procedure was performed at the L3–4 interspace using the needle-through-needle technique.

Results: There were no differences in time to readiness or intraoperative level of sensory block between the two groups. The postoperative sensory level was maintained at a higher level in the double group than in the single group (1 h postoperatively, P = 0.029; 6 h postoperatively, P = 0.016). There was no difference between the two groups in terms of side effects. The parturient satisfaction scores 48 h postoperatively were significantly different between groups (9.5 in the double group vs. 8 in the single group, P = 0.004).

Conclusions: We conclude that there were no differences in intraoperative variables between the double-space technique and the single-space technique for CSEA. However, double-space CSEA for cesarean section may be beneficial for controlling postoperative pain and improving parturient satisfaction.

Trial registration: The study was retrospectively registered at https://cris.nih.go.kr under the trial ID KCT0002514. Date of registration: October 27, 2017.
Effectiveness and feasibility of Heavy Slow Resistance Training in patients with subacromial shoulder pain. A single-blind, randomized pilot study.
Authors: Kvalvaag Elisabeth , Høiland Hans Hugo Fredriksen , Johnsen Marianne Bakke , Brox Jens Ivar , Engebretsen Kaia Beck , Røe Cecilie 
Published: January 2020

Abstract
Background Subacromial shoulder pain is the most common shoulder diagnosis, and should preferably be treated non-operatively. Previous studies have shown promising results of Heavy Slow Resistance training (HSR) in patellar and Achilles tendinopathy, but few studies have evaluated the effect of HSR for shoulder pain. The purpose of this pilot trial was to evaluate if HSR training is feasible for patients with subacromial shoulder pain, and to compare the effect of HSR to traditional supervised exercises on pain and function of the shoulder. Methods Twenty-two patients with subacromial shoulder pain lasting at least three months were recruited and randomized to HSR (n=11) or traditional supervised exercises (n=11) by computer-generated randomization in blocks of four. Patients received HSR once a week, in addition to home-training twice a week, or supervised exercises twice a week for 12 weeks, in addition to daily home-training. The primary outcome measure was the Shoulder Pain and Disability Index (SPADI). Linear regression analysis was applied to evaluate the between group differences after 12 weeks. Outcome assessors were masked.Results After 12 weeks, patients in both groups had improved significantly from baseline in SPADI score (P=0.001) but no group difference was found (mean difference 1.3; 95% CI, -21.9 to 24.5, P=0.91). Similar non-significant results between groups were seen for pain in activity and rest, and the DASH score. Conclusion This pilot-study observed no difference in effectiveness of HSR compared to supervised exercises for patients with subacromial shoulder pain and both groups improved significantly from baseline. Based on this, HSR appears to be as feasible and effective as supervised exercises for this patient group, but studies with larger sample size is required.
Influence of genetic polymorphisms in homocysteine and lipid metabolism systems on antidepressant drug response
Authors: Yuan Baoyu , Sun Xiaoyan , Xu Zhi , Pu Mengjia , Yuan Yonggui , Zhang Zhijun 
Published: January 2020

Abstract
Background Chronic lesions of small blood vessels and capillaries may play a role in the pathogenesis of depression. As the genes associated with these vascular risk factors may be involved in depression, these genetic polymorphisms may affect the efficacy of antidepressants. This study was performed to investigate the roles of methylenetetrahydrofolate reductase (MTHFR), apolipoprotein E (ApoE), and apolipoprotein A4 (ApoA4) genetic polymorphisms in antidepressant response in depressive patients.Methods A total of 281 Han Chinese patients received a single antidepressant drug for at least 6 weeks. The Hamilton Depression Rating Scale (HAMD-17) was used to evaluate the severity of depressive symptoms and the therapeutic effects of the drug administered. Eight single nucleotide polymorphisms (SNPs) of MTHFR, ApoE, and ApoA4 genes were detected using gene chips. Differences in clinical variables between the responders and non-responders, as well as between remission and non-remission groups, were examined using the independent samples t test and Pearson’s χ 2 test. In addition, the associations of single loci and haplotypes with treatment response were analyzed.Results Among the eight SNPs in four genes, two SNPs (ApoA4 rs5101 and rs675) were eliminated as they had a MAF < 5%.Haplotype(C-A) in MTHFR (rsl801133 and rs1801131) was significantly associated with better antidepressant response in the 8-week antidepressant group overall ( P = 0.0007), and in the male subgroup ( P = 0.003), and serotonin norepinephrine reuptake inhibitor (SNRI) subgroup ( P = 0.001). The ApoE rs405509 C allele was significantly associated with poorer antidepressant response in the 6-week male subgroup ( P = 0.004), while the 405509 AA genotype was associated with better antidepressant efficacy in the 6-week antidepressant group overall ( P = 0.006) and male subgroup ( P = 0.002).Conclusions Genetic polymorphisms of MTHFR, ApoE, and ApoA4 may be associated with the efficacy of antidepressants, in which the haplotype (rs1801131-rs1801133) A–C type was associated with better antidepressant efficacy, especially in males and in patients using SNRIs. The efficacy of antidepressants may be better in ApoE rs405509 A allele and AA genotype carriers, but worse in ApoA4 rs5092 G allele and GG genotype carriers.
Validity and Item Response Theory Properties of the Patient Health Questionnaire-9 for Primary Care Depression Screening in Mozambique (PHQ-9-MZ)
Authors: Cumbe Vasco Francisco Japissane , Muanido Alberto Gabriel , Manaca Maria Nélia , Fumo Hélder , Chiruca Pedro , Hicks Leecreesha , Mari Jair de Jesus , Wagenaar Bradley H 
Published: January 2020

Abstract
Background: Depression is one of the leading causes of disability in Mozambique; however, few patients with depression are identified in primary care. To our knowledge, there are no validated tools for depression screening in Mozambique. The aim of this study was to validate the Patient Health Questionnaire-9 (PHQ-9) for use in primary care settings in Mozambique.
Methods: The PHQ-9 was adapted using a structured multi-phase process led by a team of bilingual experts followed by a review by lay individuals and pilot-testing including cognitive interviews. The final Mozambican PHQ-9 (PHQ-9-MZ) was applied among 503 individuals randomly selected from antenatal, postpartum, and general outpatient consultations in three Ministry of Health primary healthcare clinics in Sofala Province, Mozambique. The PHQ-9-MZ was evaluated against the MINI 5.0-MZ as a gold standard diagnostic tool.
Results: The majority of participants were female (74%), with a mean age of 28. Using the MINI 5.0-MZ, 43 (9%) of the sample tested positive for major depressive disorder. Items of the PHQ-9-MZ showed good discrimination and factor loadings. One latent factor of depression explained 54% of the variance in scores. Questions 3 (sleep) and 5 (appetite) had the lowest item discrimination and factor loadings. The PHQ-9-MZ showed good internal consistency, with a Cronbach’s alpha of 0.84, and an area under the receiver operating characteristic curve (AUROC) of 0.81 (95% CI: 0.73, 0.89). The PHQ-2-MZ had an AUROC of 0.78 (95% CI: 0.70, 0.85). Using a cut-point of ≥9, the PHQ-9-MZ had a sensitivity of 46.5% and a specificity of 93.5%. Using a cut-point of ≥2, the PHQ-2-MZ had a sensitivity of 74.4% and a specificity of 71.7%. Increasing the cut-point to ≥3, the PHQ-2-MZ has a sensitivity of 32.6% and a specificity of 94.6%.
Conclusions: The PHQ-9-MZ and PHQ-2-MZ emerge as two valid alternatives for screening for depression in primary health care settings in Mozambique. Depending on program needs and weighing the value of minimizing false positives and false negatives, the PHQ-9-MZ can be employed with cut-points ranging from ≥8 to ≥11, and the PHQ-2-MZ with cut-points ranging from ≥2 to ≥3.
The analysis of groundwater nitrate pollution and health risk assessment in Rural Areas of Yantai
Authors: Yu Guimei , Wang Song song , Wang Jiu , Liu Lei , Li Yun , Zhang Yi 
Published: January 2020

Abstract
Background: Nitrate is one of the most common chemical contaminants of groundwater, and it is an important unqualified factor of rural groundwater in Yantai. In order to assess the risk of exposure to drinking water nitrate for adults and juveniles, in recent years, we monitored the nitrate concentrations in rural drinking water, the HHRA model was also used to assess the human health risk of nitrate pollution in groundwater. Methods : From the year 2015 to 2018, the drinking water in rural areas of Yantai was tested according to the "Sanitary Standard for Drinking Water" (GB5749-2006). The principal component analysis was used to analyze the relationship between groundwater chemicals and nitrate. The HHRA model was used to assess human health risks of groundwater nitrate through the drinking water and skin contact. Results : A total of 2348 samples were tested during the year 2015-2018.Nitrate and total dissolved solids, total hardness, chloride are all relevant, the above indicators may come from the same source of pollution; The median nitrate content (C EXP50 ) was 17.8 mg / L; the C EXP95 was 53.4 mg / L; the risk of exposure in each group was ranked as: Juveniles > Adult female > Adult male;hazard quotient HQ 50 and HQ 95 for minors and adults exceed 1. Conclusions :The concentrations of nitrate is stable and does not change over time.The high concentration of nitrate in rural areas of Yantai may be the result of the interaction of fertilizers and geological factors. The risk of exposure to nitrate in juveniles and adults is above the limit, and HQ is over 1, so it is necessary to be on the alert for the high levels of nitrate.
Transcriptome analysis and molecular mechanism of linseed (Linum usitatissimum L.) drought tolerance under repeated drought using single-molecule long-read sequencing
Authors: Wang Wei , Wang Lei , Wang Ling , Tan Meilian , Ogutu Collins O. , Yin Ziyan , Zhou Jian , Wang Jiaomei , Wang Lijun , Yan Xingchu 
Published: January 2020

Abstract
Background Oil flax (Linum usitatissimum L.) also as known as linseed is one of the most important oil crops in the world. Although linseed was reported to show better tolerance to abiotic stress conditions compared to other oil crops, the molecular mechanisms underlying linseed tolerance to drought stress are largely unknown. Moreover, as a result of climate change, drought dramatically reduces linseed yield and quality, but so far very little is known about how linseed coordinates the drought-resistant genes expression of response to different level of drought stress on the genome-wide level. Results To explore the transcriptional response of linseed to drought stress (DS) and repeated drought stress (RD), we first determined the drought tolerance of different linseed varieties. Then we performed full-length transcriptome sequencing of drought-resistant variety (Z141) and drought-sensitive variety (NY-17) using single-molecule real-time sequencing and RNA-sequencing under drought stress (DS) and repeated drought stress (RD) at the seedling stage. Gene Ontology (GO) enrichment analysis showed that compared with NY-17, the up-regulated genes of Z141 were enriched in more functional pathways related to plant drought tolerance under drought stress. In addition, the number of up-regulated genes in linseed under RD was more 30% than it under DS. In addition, a total of, 4,436 linseed transcription factors were identified, of these, 1,190 genes were responsive to stress treatments. Finally, the expression patterns of proline biosynthesis and DNA repair structural genes were verified by RT- PCR. Conclusions Drought tolerance of Z141 may be related to its specifically up-regulated drought tolerance genes under drought stress. Several variable physiological responses occurred in repeated than in sustained drought treatment. Sum up, this study provides a new perspective to understand the drought adaptability of linseed.
Downregulation of Calreticulin and Annexin A2 in Cholesteatoma by 2-DE Analysis
Authors: Ho Kuen-Yao , Hung Kuo-Feng , Chien Chen-Yu , Chai Chee-Yin , Chen Wan-Tzu , Wang Hsun-Mo , Tsai Shih-Meng , Chan Leong-Perng , Chang Ning-Chia , Wu Yu-Jen 
Published: January 2020

Abstract
Background:
Many factors are thought to be associated with the development of cholesteatoma, while the mechanisms of its formation remain unclear. This study aimed to identify the potential mechanisms of the proliferation and growth of cholesteatoma by analysis of the differential expressions of proteins in cholesteatoma and retroauricular skin tissue collected from patients.
Methods:
Comparative proteomics analyses using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), in addition to immunohistochemical analysis, were conducted to identify differentially-expressed proteins in cholesteatoma tissue as compared with retroauricular skin tissue. Western blotting was also employed to verify the expression patterns of the specific proteins identified by 2-DE and to measure the changes in potential modulators related to cholesteatoma proliferation and growth.
Results:
Calreticulin (CRT) and annexin A2 (AnxA2) were identified as being differentially-expressed in cholesteatoma by 2-DE and LC-MS/MS, the results of which were in agreement with the results of immunohistochemical analysis and western blotting. Downregulation of CRT and AnxA2 were observed in cholesteatoma.
Conclusion:
Our data suggested that CRT and AnxA2 were associated with cholesteatoma. We speculated that the reduced expression of CRT and the persistent inflammatory response play important roles in the epithelial proliferation of cholesteatoma.
Loss of HtrA2/Omi protease activity induces mitonuclear imbalance and sarcopenia via differential regulation of mitochondrial biogenesis
Authors: Zhou Haohan , Yuan Danni , Gao Weinan , Tian Jiayi , Sun Hongyu , Yu Shuang , Sun Liankun , Wang Jincheng 
Published: January 2020

Abstract
Background Cellular homeostasis requires tight coordination between nucleus and mitochondria, organelles that each possess their own genomes. Disrupted mitonuclear communication has been found to be implicated in many aging processes. However little is known about mitonuclear signaling regulator in sarcopenia which is a major contributor to the risk of poor health-related quality of life, disability and premature death in older people. HtrA2/Omi is a mitochondrial protease and play an important role in mitochondrial proteostasis. HtrA2 mnd2(-/-) mice harboring protease-deficient HtrA2/Omi Ser276Cys missense mutants exhibit premature aging phenotype. Additionally, HtrA2/Omi has been established as a signaling regulator in nervous system and tumors. We therefore asked whether HtrA2/Omi participates in mitonuclear signaling regulation in aging muscle.Methods Using motor functional, histological and molecular biological methods, we characterized the muscle phenotype of HtrA2 mnd2(-/-) mice. We employed bioinformatics analysis and identified HtrA2/Omi as a gene differentially associated with nDNA/mtDNA gene expression in sarcopenia. Further, we isolated the gastrocnemius muscle of HtrA2 mnd2(-/-) mice and determined expression of genes in UPR mt , mitohormesis, electron transport chain (ETC), and mitochondrial biogenesis.Results Here, we showed that HtrA2/Omi protease deficiency induced denervation-independent skeletal muscle degeneration. Despite of mitochondrial hypofunction, upregulation of UPR mt and mitohormesis related genes and elevated reactive oxygen species (ROS) production were not observed in HtrA2 mnd2(-/-) mice, contrary to previous assumptions that loss of protease activity of HtrA2/Omi would lead to mitochondrial dysfunction as a result of proteostasis disturbance and ROS burst. Instead, we showed that HtrA2/Omi protease deficiency results in different changes between the expression of nDNA and mtDNA encoded ETC subunits, which is in consistent with their transcription factors NRF-1/2 and coactivator PGC-1α, suggesting that HtrA2/Omi protease activity may differentially regulate mitonuclear signaling via mitochondrial biogenesis in sarcopenia. Besides, Akt1 but not GSK3β showed increased expression level in HtrA2 mnd2(-/-) muscles, indicating an involvement of Akt1 in PGC-1α regulation response to HtrA2/Omi protease deficiency.Conclusions HtrA2/Omi protease deficiency induces mitonuclear imbalance and sarcopenia via differential regulation of mitochondrial biogenesis. The novel mechanistic insights may be of importance in developing new therapeutic strategies for sarcopenia.