bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics behind disjunct distribution, hotspot-edge refugia, and discordant RADseq/mtDNA variability: insights from the Emei mustache toad
Authors: Zheng Yuchi , Dai Qiang , Guo Xianguang , Zeng Xiaomao
Published: August 2020

Background

The distribution of genetic diversity and the underlying processes are important for conservation planning but are unknown for most species and have not been well studied in many regions. In East Asia, the Sichuan Basin and surrounding mountains constitute an understudied region that exhibits a “ring” of high species richness overlapping the eastern edge of the global biodiversity hotspot Mountains of Southwest China. We examine the distributional history and genetic diversification of the Emei mustache toad Leptobrachium boringii, a typical “ring” element characterized by disjunct ranges in the mountains, by integrating time-calibrated gene tree, genetic variability, individual-level clustering, inference of population splitting and mixing from allele frequencies, and paleoclimatic suitability modeling.

Results

The results reveal extensive range dynamics, including secondary contact after long-term isolation via westward dispersal accompanied by variability loss. They allow the proposal of a model that combines recurrent contractions caused by Quaternary climatic changes and some failed expansions under suitable conditions for explaining the shared disjunct distribution pattern. Providing exceptional low-elevation habitats in the hotspot area, the eastern edge harbors both long-term refugial and young immigrant populations. This finding and a synthesis of evidence from other taxa demonstrate that a certain contributor to biodiversity, one that preserves and receives low-elevation elements of the east in this case, can be significant for only a particular part of a hotspot. By clarifying the low variability of these refugial populations, we show that discordant mitochondrial estimates of diversity can be obtained for populations that experienced admixture, which would have unlikely left proportional immigrant alleles for each locus.

Conclusions

Dispersal after long-term isolation can explain much of the spatial distribution of genetic diversity in this species, while secondary contact and long-term persistence do not guarantee a large variation. The model for the formation of disjunct ranges may apply to many other taxa isolated in the mountains surrounding the Sichuan Basin. Furthermore, this study provides insights into the heterogeneous nature of hotspots and discordant variability obtained from genome-wide and mitochondrial data.
Plasma trimethylamine n-oxide is associated with renal function in patients with heart failure with preserved ejection fraction
Authors: Guo Fei , Qiu Xueting , Tan Zhirong , Li Zhenyu , Ouyang Dongsheng
Published: August 2020

Background

Heart failure with preserved ejection fraction (HFpEF) is an emerging global health problem with less awareness. Renal dysfunction in HFpEF is associated with worse outcome. However, there is lack of rapid, noninvasive and accurate method for risk stratification in HFpEF and renal dysfunction. This study aimed to explore the utility of plasma trimethylamine n-oxide (TMAO) for evaluation of HFpEF and renal function.

Methods

Plasma TMAO levels were measured in total 324 subjects comprising 228 HFpEF patients and 96 healthy controls.

Results

TMAO levels were significantly elevated in patients with HFpEF compared with controls (12.65(9.32–18.66) μg/l vs 10.85(6.35–15.58) μg/l, p <  0.01). Subjects in higher TMAO tertile group had more incidences of HFpEF ((78.5%) in tertile 3 vs (73.39%) in tertile 2 vs (59.26%) in tertile 1, p <  0.01). TMAO concentrations were inversely correlated with estimated glomerular filtration rate (eGFR) and HFpEF patients with impaired renal function (eGFR < 60 ml/min/1.73 m2) had higher TMAO than those with normal eGFR (≥ 60 ml/min/1.73 m2) (14.18(10.4–23.06) μg/l vs 10.9(7.48–15.47) μg/l, p < 0.01). Increased TMAO levels were independently associated with higher risk of HFpEF (OR = 3.49, 95% CI: 1.23–9.86, p = 0.02) and renal dysfunction (OR = 9.57, 95% CI: 2.11–43.34, p < 0.01) after adjustment for multiple traditional risk factors. Furthermore, TMAO had good performance at distinguishing HFpEF from controls (AUC = 0.63, p < 0.01), and renal dysfunction from normal renal function in HFpEF (AUC = 0.67, p < 0.01).

Conclusion

In this cross-sectional study, HFpEF and renal function were closely related with plasma TMAO levels and TMAO may serve as a diagnostic biomarker for HFpEF and renal function.
Inference about time-dependent prognostic accuracy measures in the presence of competing risks
Authors: Dey Rajib , Sebastiani Giada , Saha-Chaudhuri Paramita
Published: August 2020

Background

Evaluating a candidate marker or developing a model for predicting risk of future conditions is one of the major goals in medicine. However, model development and assessment for a time-to-event outcome may be complicated in the presence of competing risks. In this manuscript, we propose a local and a global estimators of cause-specific AUC for right-censored survival times in the presence of competing risks.

Methods

The local estimator - cause-specific weighted mean rank (cWMR) - is a local average of time-specific observed cause-specific AUCs within a neighborhood of given timet. The global estimator - cause-specific fractional polynomials (cFPL) - is based on modelling the cause-specific AUC as a function oftthrough fractional polynomials.

Results

We investigated the performance of the proposed cWMR and cFPL estimators through simulation studies and real-life data analysis. The estimators perform well in small samples, have minimal bias and appropriate coverage.

Conclusions

The local estimator cWMR and the global estimator cFPL will provide computationally efficient options for assessing the prognostic accuracy of markers for time-to-event outcome in the presence of competing risks in many practical settings.
EUS in the diagnosis of pathologically undiagnosed esophageal tuberculosis
Authors: Zhu Rong , Bai Yonghua , Zhou Yuankun , Fang Xingguo , Zhao Kui , Tuo Biguang , Wu Huichao
Published: August 2020

Background

Esophageal tuberculosis (ET) is relatively rare, and the diagnosis is challenging. The aim of this study was to evaluate the clinical features of ET and highlight the role of endoscopic ultrasonography (EUS) in the diagnosis of pathologically undiagnosed ET.

Methods

We retrospectively analysed the clinical features, radiological performances, conventional endoscopic appearances, EUS features, treatment and outcomes of pathologically undiagnosed ET between January 2011 and December 2018. All 9 patients failed to be diagnosed by at least two repeated biopsies (such as routine biopsy, multipoint or deep biopsy, and even or EUS-guided fine-needle aspiration (EUS-FNA)).

Results

Nine patients (66.7% female) with a mean age of 45 years (range 29–59) complained of retrosternal pain or discomfort, or (and) dysphagia. Esophagoscopy demonstrated protruding lesions in the mucosa with central ulcers or erosion in five patients, submucosal bulges with smooth surfaces in one patient, submucosal bulges with diverticula in one patient, ulcers with suspicious fistula formation in one patient, and multiple ulcers in one patient. None of the patients received confirmed histopathological or bacteriological diagnoses by repeated biopsies. However, they were first suspected to have ET based on EUS examination. Because EUS found some characteristic ultrasonographic changes, which were very helpful for the diagnosis of ET when combined with clinical manifestations, the patients subsequently received diagnostic antituberculosis therapy. Finally, the patients recovered or improved with follow-up times ranging from 3 to 10 months.

Conclusions

EUS could help in the diagnosis of ET on basis of EUS features like poorly defined esophageal wall structure, enlarged paraesophageal or mediastinal lymph nodes, hypoechoic lesions of esophageal wall that are linked to the enlarged paraesophageal lymph nodes. However all attempts should be made to obtain histological or microbiological diagnosis.
Investigating the needs of family caregivers of older stroke patients: a longitudinal study in Iran
Authors: Farahani Mansoureh Ashghali , Bahloli Shiva , JamshidiOrak Roohangiz , Ghaffari Fatemeh
Published: August 2020

Background

The high burden of care associated with older stroke patients is a factor that threatens the health of family caregivers. Identifying the needs of family caregivers in this group of patients can help provide effective solutions. The present study aimed to determine the needs of family caregivers of older stroke patients.

Methods

The sample size of this longitudinal study included 200 family caregivers of older stroke patients from two hospitals in Iran. Data collection included demographics, responses to family caregivers’ needs questionnaires, and the Barthel Index which was taken in four stages including admission time, pre-discharge, two weeks and 12 weeks post-discharge.

Results

The results showed that all participants at all stages of the study identified “respect for the patient when providing education, treatment, or rehabilitation” as one of their needs. There was a statistically significant relationship between the older adult survivor’s age and the number of family caregivers’ needs two weeks post-discharge (p = 0.012) and 12 weeks post-discharge (p = 0.008). There was a significant relationship between the patient’s hospitalization period and the number of caregivers’ needs three months after the patient’s discharge (p = 0.028), and a significant statistical relationship between the pre-discharge physiotherapy of the patients and the number of their caregivers’ needs during the two weeks post-discharge (p = 0.018). There was also a statistically significant relationship between the patient’s level of dependence and the number of caregivers’ needs (p = 0.0001). On the contrary, there was no significant relationship between the sex, place of living, and underlying disease history of the patient and the number of caregivers’ needs (p > 0.05).

Conclusion

The results of the present research indicate that the total number of caregivers’ needs decreases with increasing duration of the disease. However, respite and care provision planning by other family members, seeking assistance from professional caregivers, and the search for community support resources can help reduce the burden of care of caregivers and give them the opportunity to meet their needs in different dimensions of patient care provided.
A case report of adult-onset COQ8B nephropathy presenting focal segmental glomerulosclerosis with granular swollen podocytes
Authors: Maeoka Yujiro , Doi Toshiki , Aizawa Masaho , Miyasako Kisho , Hirashio Shuma , Masuda Yukinari , Kishita Yoshihito , Okazaki Yasushi , Murayama Kei , Imasawa Toshiyuki , Hara Shigeo , Masaki Takao
Published: August 2020

Background

Primary coenzyme Q10 (CoQ10) deficiency of genetic origin is one of a few treatable focal segmental glomerulosclerosis (FSGS). Renal morphologic evidence for COQ8B mutation and CoQ10 deficiencies of other gene mutations is assessed using electron microscopy with marked increase of abnormal-shaped mitochondria in podocytes. However, light microscopic morphologic features of deficiencies other than FSGS have not been reported.

Case presentation

A 30-year-old woman was admitted to our hospital because proteinuria was found during four consecutive medical checkups. She had no medical history or family history of proteinuria and severe renal dysfunction. The swollen podocytes were stained to the same extent as mitochondria-rich proximal tubular cells under both Masson’s trichrome and hematoxylin-eosin staining, whereas no mitochondrial abnormalities were detected under the first electron microscopic views. As proteinuria and estimated glomerular filtration rate (eGFR) deteriorated after pregnancy, we reevaluated the additional electron microscopic views and detected mitochondrial abnormalities. Genetic testing revealed COQ8B mutation (c.532C > T, p.R178W); therefore, we diagnosed COQ8B nephropathy. CoQ10 supplementation improved proteinuria and stopped eGFR reduction.

Conclusions

This is the first report of granular swollen podocytes due to mitochondrial diseases detected under light microscopy. We propose that this finding can be the clue for the diagnosis of both COQ8B nephropathy and the other CoQ10 deficiencies.
Refractive surprise after cataract surgery secondary to smeared optics of swept-source optical coherence tomography biometer: a case report
Authors: Carr Francis , Gangwani Vinod
Published: August 2020

Background

Inaccurate biometry can lead to the wrong intraocular lens implantation and result in refractive surprise following cataract surgery. It is important to be sceptical of biometry results that do not match the refractive or clinical picture and ask for it to be repeated.

Case presentation

We present a unique cause of refractive surprise in a patient undergoing cataract surgery. Pre-operative refraction demonstrated hypermetropia, yet swept-source optical coherence tomography (SS-OCT) biometry repeatedly calculated the axial length as > 35.00 mm in both eyes. The patient underwent phacoemulsification and intraocular lens insertion using the provided biometry calculations, however post-operatively the patient had a + 14.00 dioptre refractive surprise. Analysis of biometry performed on the same day identified other patients with exaggerated axial lengths, supporting the theory that the biometer’s smeared optical surface was responsible. Following servicing of the machine, repeat biometry of the patient calculated the axial length consistent with a hypermetrope (21.67 mm) and the intraocular lens exchange was successful in correcting the refractive error.

Conclusions

Ensure the optical surfaces of the biometer are cleaned regularly, and consider repeating biometry on separate days if repeat biometry still is not in keeping with the refractive or clinical picture. Additionally, re-confirm the axial length with another modality.
Cost-effectiveness and accuracy of cervical cancer screening with a high-risk HPV genotyping assay vs a nongenotyping assay in China: an observational cohort study
Authors: Dong Binhua , Chen Lihua , Lin Wenyu , Su Yingying , Mao Xiaodan , Pan Diling , Ruan Guanyu , Xue Huifeng , Kang Yafang , Sun Pengming
Published: August 2020

Background

New screening techniques may affect the optimal approaches for the prevention of cervical cancer. We evaluated the cost-effectiveness and accuracy of alternative screening strategies to provide evidence for cervical cancer screening guidelines in China.

Methods

In total, 32,306 women were enrolled. The current screening with Cervista®high-risk human papillomavirus (HR-HPV) nongenotyping and cytology cotesting (Cervista®cotesting) was compared with PCR-reverse dot blot HR-HPV genotyping and cytology cotesting (PCR-RDB cotesting). All eligible participants were divided into Arm 1, in which both HR-HPV assays were performed, and Arms 2 and 3, in which the PCR-RDB HPV or Cervista®HR-HPV assay, respectively, was performed. Outcome indicators included the cases, sensitivity, negative predictive value (NPV), colposcopy referral rate and cost of identifying cervical intraepithelial neoplasia of grade 2/3 or worse (CIN2+/CIN3+).

Results

Among the eligible participants, 18.4% were PCR-RDB HR-HPV-positive, while 16.9% were Cervista®HR-HPV-positive, which reflects good agreement (k = 0.73). PCR-RDB cotesting identified more CIN3+ cases than Cervista®cotesting in the first round of screening in Arm 1 (37 vs 32) and Arms 2/3 (252 vs 165). The sensitivity and NPV of PCR-RDB cotesting for identifying CIN3+ in Arm 1 (sensitivity: 94.9% vs 86.5%; NPV: 99.9% vs 99.7%) and Arms 2/3 (sensitivity: 95.1% vs 80.9%; NPV: 99.9% vs 99.6%) were higher than those of Cervista®cotesting, but the cost was similar.

Conclusions

The PCR-RDB HR-HPV genotyping and Cervista®HR-HPV assay results were consistent. PCR-RDB cotesting possesses optimal cost-effectiveness for cervical cancer screening in China, which has the highest number of cases globally but low screening coverage.
Perceived stress and diet quality in women of reproductive age: a systematic review and meta-analysis
Authors: Khaled Karim , Tsofliou Fotini , Hundley Vanora , Helmreich Rebecca , Almilaji Orouba
Published: August 2020

Background

Poor diet quality is associated with obesity-related morbidity and mortality. Psychological stress can increase unhealthy dietary choices, but evidence pertinent to women of reproductive age remains unclear. This paper systematically reviewed the literature to determine the association between psychological stress and diet quality in women of reproductive age.

Methods

Medline, CINAHL, Scopus, Cochrane Library, Web of Science, and Sciencedirect were searched. Data extraction was determined by the PEO. Inclusion criteria consisted of: English language, stress (exposure) measured in combination with diet quality (outcome), healthy women of reproductive age (18–49 years old (population)). Observational studies, due to the nature of the PEO, were included. Quality assessment used the Risk of Bias in Non-randomised Studies from the Cochrane Handbook of Systematic Reviews of Interventions. Meta-analysis was conducted using random-effect model to estimate the Fisher’s z transformed correlation between stress and diet quality with 95% confidence interval (CI).

Results

From 139,552 hits, 471 papers were screened; 24 studies met the inclusion criteria and were conducted in different countries: 8 studies on diet quality and 16 on food intake and frequency of consumption. Studies of diet quality consisted of six cross-sectional and two longitudinal designs with a total of 3982 participants. Diet quality was measured with diverse indices; Alternate Healthy Eating Index (n = 2), Healthy Eating Index (n = 2), Dietary Approach to Stop Hypertension (DASH) Diet Index (n = 2), Dietary Quality Index- Pregnancy (n = 2), and Dietary Guideline Adherence Index (n = 1). Most studies used Cohen’s perceived stress scale and no study measured biological stress response. After sensitivity analysis, only 5 studies (3471 participants) were included in the meta-analysis. Meta-analysis revealed a significant negative association between stress and diet quality with substantial heterogeneity between studies (r = − 0.35, 95% CI [− 0.56; − 0.15], p value < 0.001, Cochran Q test P < 0.0001, I2 = 93%).

The 16 studies of food intake and frequency of consumption were very heterogeneous in the outcome measure and were not included in the meta-analysis. These studies showed that stress was significantly associated with unhealthy dietary patterns (high in fat, sweets, salt, and fast food and low in fruits, vegetables, fish, and unsaturated fats).

Conclusion

Future studies that explore diet quality/patterns should include both diet indices and factor analysis and measure biological markers of stress and dietary patterns simultaneously.
Socioeconomic status, social capital, health risk behaviors, and health-related quality of life among Chinese older adults
Authors: Yang Ying , Wang Shizhen , Chen Lei , Luo Mi , Xue Lina , Cui Dan , Mao Zongfu
Published: August 2020

Background

There is limited knowledge on the mediating role of different health risk behavior on the relationship between social capital, socioeconomic status (SES), and health-related quality of life (HRQoL) in Chinese older adults. We conducted this study to (a) investigate the condition of health risk behaviors of the Chinese elderly, and (b) assess the relationship between SES, social capital, health risk behaviors, and HRQoL.

Methods

A sample of 4868 adults aged 60 years and older were included in this study, from the China’s Health-related Quality of Life Survey for Older Adults 2018. Participants’ demographic characteristics, SES (education level, family income), health risk behaviors (smoking, alcohol consumption, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder) were collected. Social capital and HRQoL were assessed by the 16-item Personal Social Capital Scale (PSCS-16) and WHOQOL-Old, respectively. Structural equation modeling (SEM) was applied to examine the associations between variables.

Results

The proportion of smoking, alcohol consumption, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder were 32.1, 36.3, 62.5, 45.7, 31.8, and 45.5%, respectively. Significant differences were observed in education level, family income, and social capital between elderly individuals with and without each of the six health risk behavior (all p-values < 0.05). Elderly individuals who reported smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder had significantly lower HRQoL than those without these unhealthy behaviors (all p-values < 0.05). SEM analysis showed that SES and social capital positively associated with alcohol consumption. Social capital negatively associated with smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder. SES negatively associated with smoking, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder. Smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder correlated with poorer HRQoL.

Conclusions

Chinese older adults demonstrated a high incidence of health risk behaviors, especially for physical inactivity (62.5%) and unhealthy dietary behavior (45.7%). Social capital and SES were correlated with the elderly’s HRQoL, as well as with the health risk behaviors. Health risk behaviors played potential mediating role on the relationship between social capital, SES, and HRQoL in Chinese older adults.
Cost-effectiveness evaluation of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine for children in Taiwan
Authors: Lu Chun-Yi , Chung Ching-Hu , Huang Li-Min , Kruger Eliza , Tan Seng-Chuen , Zhang Xu-Hao , Chiu Nan-Chang
Published: August 2020

Background

Streptococcus pneumoniae (S. pneumoniae)and non-typeableHaemophilus influenzae(NTHi) are substantial contributors to morbidity and mortality of diseases including invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) worldwide. In Taiwan, 10-valent pneumococcal polysaccharide and NTHiprotein D conjugate vaccine (PHiD-CV) and 13-valent pneumococcal conjugate vaccine (PCV13) are licensed in children against pneumococcal disease. In addition toS. pneumoniae, clinical trials suggest efficacy of PHiD-CV against NTHiAOM. This study aims at evaluating the cost-effectiveness of a 2 + 1 schedule of PHiD-CV vs. PCV13 2 + 1 in the universal mass vaccination program of infants in Taiwan.

Methods

A published Markov cohort model was adapted to simulate the epidemiological burden of IPD, pneumonia and AOM for a birth cohort in Taiwan over 10 years. The probability of entering a specific health state was based on the incidence rate of the diseases. Only direct medical costs were included, and costs and outcomes were discounted annually. Vaccine efficacy assumptions were based on published data and validated by a panel of independent experts. Clinical, epidemiological, and serotype distribution data were based on locally published data or the National Health Insurance Research Database. Price parity of vaccines was assumed. Published pneumococcal disease-related disutility weights were used due to lack of local data. Incremental cost-effectiveness ratio was calculated and benchmarked against the recommended threshold in Taiwan. Extensive one-way sensitivity analysis, alternative scenarios and probabilistic sensitivity analysis were performed to test the robustness of the results.

Results

PHiD-CV would potentially reduce the number of NTHi-related AOM cases substantially and prevent comparable IPD and pneumonia-related cases and deaths compared to PCV13. Over a 10-year horizon, PHiD-CV is estimated to dominate PCV13, saving 8.8 million New Taiwan Dollars (NTD) and saving 21 quality-adjusted life years. The result was robust over a wide range of sensitivity analyses. The dominance of PHiD-CV was demonstrated in 61% of the simulations.

Conclusions

PHiD-CV 2 + 1 would provide comparable prevention of IPD, pneumonia cases and additional reduction of NTHi-AOM cases, and is considered dominant compared with PCV13 2 + 1 in Taiwan.
The role of carbon ion radiotherapy for unresectable locally recurrent rectal cancer: a single institutional experience
Authors: Cai Xin , Du Yueyao , Wang Zheng , Li Ping , Yu Zhan , Zhang Qing , Zhang Zhen
Published: August 2020

Background

Treatment for locally recurrent rectal cancer after surgery is still a challenge. With the physical and biological advantages, carbon-ion radiotherapy (CIRT) could be a choice for these patients. The purpose of this study was to investigate the efficacy and safety of CIRT for unresectable locally recurrent rectal cancer in Chinese patients.

Methods

Date from 25 patients with unresectable locally recurrent rectal cancer treated by CIRT from July 2015 to April 2019 were analyzed retrospectively. The endpoints of this study were overall survival (OS), local control (LC) and acute and late toxicity.

Results

With the median follow-up of 19.6 (range 5.1–52.5) months, data of all 25 patients were collected. Median prescribed dose for tumor was 72Gy (relative biologic efficacy (RBE)) (range 48–75.6Gy (RBE)). The LC rates at 1 and 2 years were 90.4 and 71.8%. Overall LC at 1- and 2-year were 76.2 and 30.5% for 9 patients whose prescribed tumor doses of CIRT< 66 Gy (RBE), 100 and 100% for 16 patients whose prescribed doses of CIRT≥66 Gy (RBE). Patients received ≥66 Gy (RBE) had obviously better LC rates than those received < 66 Gy (RBE) (P = 0.001). The OS rates at 1 and 2 years were 82.9 and 65.1%, respectively. No acute toxicity over grade 2 was observed, grade 3 late toxicity were observed in 3 patients: gastrointestinal toxicity (n = 1), neuropathy (n = 1), pelvic infection (n = 1). No Grade 4 or higher toxicity was observed.

Conclusion

Our study shows that CIRT is effective for unresectable locally recurrent rectal cancer patients with acceptable toxicity.
Effect of bone morphogenetic protein-2/hydroxyapatite on ankle fusion with bone defect in a rabbit model: a pilot study
Authors: Dang Le Hoang Nam , Lee Kwang Bok
Published: August 2020

Background

Revision ankle-fusion surgery after a failure of total ankle arthroplasty has a problem with bone-defect management by implant removal. For the reconstruction of bone defects, autogenous bone often causes minor and major complications. Recombinant human-bone morphogenetic protein-2 (rhBMP-2) plays essential roles in bone regeneration strategies, and hydroxyapatite (HA) is beneficial as the rhBMP-2 carrier. In this study, we evaluate whether rhBMP-2/HA can replace autogenous bone in a rabbit ankle-fusion model with distal tibia bone defect.

Methods

The bone defect was created in the distal tibia. The ankle fusion was performed by a cannulated screw from lateral malleolus and various treatments on bone defect. Thirty male white New Zealand rabbits were divided into three groups of 10 animals on each group dependent on treatment methods as control group (no treatment into defect), auto-bone group (autogenous bone treatment), and rhBMP-2/HA group (40 μL of 1 μg/mL rhBMP-2/100 μL HA). Bone formation on defect and the union of the ankle joint were evaluated by X-ray, micro-CT, and histological analysis at 8 weeks and 12 weeks, postoperatively.

Results

Radiographic assessment found the control and auto-bone groups still had the bone defect present, but rhBMP-2/HA group showed complete replacement of the defect with newly formed bone at 12 weeks. Micro-CT showed significantly higher new bone formation within the defect in the rhBMP-2/HA group than in the auto-bone and control groups at 8 weeks (p > 0.05 and p < 0.01, respectively) and 12 weeks (p < 0.05, p < 0.001, respectively). Fusion rate (%) analysis of micro-CT showed a higher percentage of union in the rhBMP-2/HA group than in the auto bone and control groups at 8 weeks (p > 0.05, p < 0.001, respectively) and 12 weeks (p < 0.001 and p < 0.001, respectively). The histological showed the highest osteointegration between distal tibia and talus in the rhBMP-2/HA group at 12 weeks.

Conclusions

This study indicated that rhBMP-2/HA showed much better bone fusion than did the autogenous bone graft and was effective in promoting fusion rate and improving the quality of the ankle joint fusion.
Application of network pharmacology and molecular docking to elucidate the potential mechanism of Eucommia ulmoides-Radix Achyranthis Bidentatae against osteoarthritis
Authors: Jian Gong-hui , Su Bing-zhu , Zhou Wen-jia , Xiong Hui
Published: August 2020

Background

Osteoarthritis is a disabling disease, which seriously affects the quality of life of patients. Increasing evidence has indicated that Chinese herbal medicine includingEucommia ulmoides(EU) andRadix Achyranthis Bidentatae(RAB) have potential in the treatment of osteoarthritis, and this is associated with their multi-target and multi-link action characteristics. Although their potential anti-arthritic activity has been reported, the exact mechanism of EU-RAB action in osteoarthritis remains unexplored. Therefore, this study explores the mechanism of EU-RAB against osteoarthritis using network pharmacology and molecular docking technology.

Methods

Public databases including TCMSP、BATMAN-TCM、OMIM and Genecards were used to predict the bioactive ingredients and putative targets of EU-RAB against osteoarthritis. Enrichment analysis was performed to expound the biological functions and associated pathways of the hub targets. Cytoscape software was used to construct a “compounds-targets-pathways” network for elucidating the comprehensive molecular mechanism of EU-RAB against osteoarthritis. Molecular docking was used to verify the correlation between the main active ingredients and hub targets.

Results

Network pharmacological analysis of EU-RAB in the treatment of osteoarthritis, identified 50 active ingredients including quercetin, kaempferol, wogonin, and baicalein with important biological effect. A total of 68 key targets were screened, including IL-6, EGFR, MAPK8, etc., and they were found to be enriched in a series of signaling pathways, such as apoptosis, TNF, MAPK, PI3K/AKT, and IL-17 signaling pathways. Moreover, molecular docking analysis showed that the main ingredients were tightly bound to the core targets, further confirming the anti-arthritic effects.

Conclusion

Based on network pharmacology and molecular docking analysis, the present study provides insights into the potential mechanism of EU-RAB in osteoarthritis after successfully screening for associated key target genes and signaling pathways. These findings further provide a theoretical basis for further pharmacological research into the potential mechanism of EU-RAB in osteoarthritis.
mGluR5 regulates REST/NRSF signaling through N-cadherin/β-catenin complex in Huntington’s disease
Authors: de Souza Jéssica M. , Abd-Elrahman Khaled S. , Ribeiro Fabiola M. , Ferguson Stephen S. G.
Published: August 2020

Repressor element 1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a transcription repressor and its expression is regulated by the Wnt pathway through β-catenin. Metabotropic glutamate receptor 5 (mGluR5) signaling plays a key role in controlling neuronal gene expression. Interestingly, REST/NRSF nuclear translocation and signaling, as well as mGluR5 signaling are altered in the presence of mutant huntingtin. It remains unclear whether mGluR5 can modulate Wnt and REST/NRSF signaling under physiological conditions and whether this modulation is altered in Huntington’s disease (HD). Using primary corticostriatal neurons derived from wild type mouse embryos, we find that targeting mGluR5 using the agonist, DHPG, or the negative allosteric modulator, CTEP, modulates REST/NRSF expression by regulating the assembly of N-cadherin/ β-catenin complex in a Src kinase-dependent manner. We have validated our in vitro findings in vivo using two HD mouse models. Specifically, we show that pharmacological inhibition of mGluR5 inzQ175 mice and genetic ablation of mGluR5 in BACHD mice corrected the pathological activation of Src and rescued REST/NRSF-dependent signaling. Together, our data provide evidence that mGluR5 regulates REST/NRSF expression via the Wnt pathway and highlight the contribution of impaired REST/ NRSF signaling to HD pathology.
3DeFDR: statistical methods for identifying cell type-specific looping interactions in 5C and Hi-C data
Authors: Fernandez Lindsey R. , Gilgenast Thomas G. , Phillips-Cremins Jennifer E.
Published: August 2020

An important unanswered question in chromatin biology is the extent to which long-range looping interactions change across developmental models, genetic perturbations, drug treatments, and disease states. Computational tools for rigorous assessment of cell type-specific loops across multiple biological conditions are needed. We present 3DeFDR, a simple and effective statistical tool for classifying dynamic loops across biological conditions from Chromosome-Conformation-Capture-Carbon-Copy (5C) and Hi-C data. Our work provides a statistical framework and open-source coding libraries for sensitive detection of cell type-specific loops in high-resolution 5C and Hi-C data from multiple cellular conditions.
De novo assembly of transcriptome dataset from leaves of Dryobalanops aromatica (Syn. Dryobalanops sumatrensis) seedlings grown in two contrasting potting media
Authors: Siregar Iskandar Zulkarnaen , Dwiyanti Fifi Gus , Siregar Ulfah Juniarti , Matra Deden Derajat
Published: August 2020

Objectives

Efforts to restore tropical peat swamp forests in Indonesia face huge challenges of potential failures due to socio-economic factors and ecological dynamics attributed to lack of knowledge on the adaptive mechanisms of potential tree species such as Kapur (Dryobalanops aromatica C.F.Gaertn Syn. Dryobalanops sumatrensis J.F. Gmelin A.J.G.H Kostermans). This species is a multi-purpose tree that, commonly grows in mineral soils, but also in peat swamp as previously reported, which raised a fundamental question regarding the molecular mechanism of this adaptation. Therefore, a dataset was created aiming to detect candidates of adaptive genes in D. aromatica seedlings, cultivated in two contrasting potting media, namely mineral soil and peat media, based on RNA Sequencing Transcriptome Analysis.

Data description

The RNA transcriptome data of D. aromatica’s seedlings derived from young leaves of three one-year-old seedlings, raised in each dry mineral soil media and peat media, were generated by using Illumina HiSeq 4000 platform in NovogenAIT, Singapore. The acquired data, as the first transcriptome dataset for D. aromatica, is of a great importance in understanding molecular mechanism and responses of the involved genes of D. aromatica to the contrasting, growing potting media conditions that could also be useful to generate molecular markers.
Assessment of tumor suppressor promoter methylation in healthy individuals
Authors: Poduval Deepak B. , Ognedal Elisabet , Sichmanova Zuzana , Valen Eivind , Iversen Gjertrud T. , Minsaas Laura , Lønning Per E. , Knappskog Stian
Published: August 2020

Background

The number of tumor suppressor genes for which germline mutations have been linked to cancer risk is steadily increasing. However, while recent reports have linked constitutional normal tissue promoter methylation of BRCA1 and MLH1 to ovarian and colon cancer risk, the role of epigenetic alterations as cancer risk factors remains largely unknown, presenting an important area for future research. Currently, we lack fast and sensitive methods for assessment of promoter methylation status across known tumor suppressor genes.

Results

In this paper, we present a novel NGS-based approach assessing promoter methylation status across a large panel of defined tumor suppressor genes to base-pair resolution. The method omits the limitations related to commonly used array-approaches. Our panel includes 565 target regions covering the promoters of 283 defined tumor suppressors, selected by pre-specified criteria, and was applied for rapid targeted methylation-specific NGS. The feasibility of the method was assessed by analyzing normal tissue DNA (white blood cells, WBC) samples from 34 healthy postmenopausal women and by performing preliminary assessment of the methylation landscape of tumor suppressors in these individuals. The mean target coverage was 189.6x providing a sensitivity of 0.53%, sufficient for promoter methylation assessment of low-level methylated genes like BRCA1. Within this limited test-set, we detected 206 regions located in the promoters of 149 genes to be differentially methylated (hyper- or hypo-) at > 99% confidence level. Seven target regions in gene promoters (CIITA, RASSF1, CHN1, PDCD1LG2, GSTP1, XPA, and ZNF668) were found to be hyper-methylated in a minority of individuals, with a > 20 percent point difference in mean methylation across the region between individuals. In an exploratory hierarchical clustering analysis, we found that the individuals analyzed may be grouped into two main groups based on their WBC methylation profile across the 283 tumor suppressor gene promoters.

Conclusions

Methylation-specific NGS of our tumor suppressor panel, with detailed assessment of differential methylation in healthy individuals, presents a feasible method for identification of novel epigenetic risk factors for cancer.
Nutrient-supplemented propagation of Saccharomyces cerevisiae improves its lignocellulose fermentation ability
Authors: van Dijk Marlous , Mierke Friederike , Nygård Yvonne , Olsson Lisbeth
Published: August 2020

Propagation conditions have been shown to be of considerable importance for the fermentation ability of Saccharomyces cerevisiae. The limited tolerance of yeast to inhibitors present in lignocellulosic hydrolysates is a major challenge in second-generation bioethanol production. We have investigated the hypothesis that the addition of nutrients during propagation leads to yeast cultures with improved ability to subsequently ferment lignocellulosic materials. This hypothesis was tested with and without short-term adaptation to wheat straw or corn stover hydrolysates during propagation of the yeast. The study was performed using the industrial xylose-fermenting S. cerevisiae strain CR01. Adding a mixture of pyridoxine, thiamine, and biotin to unadapted propagation cultures improved cell growth and ethanol yields during fermentation in wheat straw hydrolysate from 0.04 g g−1 to 0.19 g g−1 and in corn stover hydrolysate from 0.02 g g−1 to 0.08 g g−1. The combination of short–term adaptation and supplementation with the vitamin mixture during propagation led to ethanol yields of 0.43 g g−1 in wheat straw hydrolysate fermentation and 0.41 g g−1 in corn stover hydrolysate fermentation. These ethanol yields were improved compared to ethanol yields from cultures that were solely short-term adapted (0.37 and 0.33 g g−1). Supplementing the propagation medium with nutrients in combination with short-term adaptation was thus demonstrated to be a promising strategy to improve the efficiency of industrial lignocellulosic fermentation.
Correlation between immunity from BCG and the morbidity and mortality of COVID-19
Authors: Wickramasinghe Dakshitha , Wickramasinghe Nilanka , Kamburugamuwa Sohan Anjana , Arambepola Carukshi , Samarasekera Dharmabandhu N.
Published: August 2020

Background

To investigate the association between parameters indicating immunity from BCG at country level (presence of BCG vaccination policy, BCG coverage, age-specific incidence of tuberculosis (TB)) and the morbidity and mortality of COVID-19.

Methods

Country-specific data for COVID-19 cases and deaths, demographic details, BCG coverage and policy, age-specific TB incidence and income level were obtained. The crude COVID-19 cases and deaths per 100,000 population were calculated and assessed against the parameters indicating immunity from BCG using linear regression analysis.

Results

Univariate analysis identified higher income level of a country to be significantly associated with COVID-19 cases (p < 0.0001) and deaths (p < 0.0001) but not with its case fatality rate. The association between COVID-19 and TB was strongest for TB incidence in patients > 65-years (Cases (rs = − 0.785,p = 0.0001)) and deaths (rs = − 0.647,p = 0.0001).

Multivariate analysis identified the higher income level of a country and not having a universal BCG vaccination policy to affect the COVID-19 cases. The deaths were inversely affected by the presence of BCG vaccination policy and coverage; and positively by the TB incidence in patients > 65-years.

Conclusion

Significant inverse correlations observed between cases and deaths of COVID-19 and BCG related parameters highlights immunity from BCG as a likely explanation for the variation in COVID-19 across countries.
Measuring the impact of chronic low back pain on everyday functioning: content validity of the Roland Morris disability questionnaire
Authors: Burbridge Claire , Randall Jason A. , Abraham Lucy , Bush Elizabeth Nicole
Published: August 2020

Background

Robust outcome measures are needed to assess and monitor the impact of chronic low back pain (CLBP) on physical functioning. The Roland Morris Disability Questionnaire (RMDQ) is a well-established measure designed to capture the impacts of back pain on everyday functioning, with a particular emphasis on physical functioning. It has documented evaluation of psychometric properties. However, there is no documented qualitative evidence to confirm the content validity of the tool, nor have changes made for electronic administration been debriefed in participants with CLBP.

Methods

In-depth, semi-structured, concept elicitation and cognitive debriefing interviews were conducted with 23 US participants with confirmed CLBP. Interviews allowed participants to describe the impact of CLBP on their day-to-day functioning and discuss comprehension and suitability of the RMDQ. Interviews were transcribed verbatim and analyzed using thematic analysis.

Results

Concept elicitation and cognitive debriefing revealed the substantial burden associated with CLBP, highlighting 15 key areas of functional impact. These were grouped into overarching themes of mobility (walking, stairs, sitting/standing, bending/kneeling, lifting, lying down), activities (chores/housework, dressing, washing, driving, work) and other (relationships/socializing, mood, sleep, appetite), which are consistent with those evaluated within the RMDQ.

All participants found the RMDQ to be relevant with most reporting that the instructions, recall period, and response options were suitable. A few suggested minor changes, however, none were consistent or necessary to support content validity. Updates to the measure for electronic administration and to clarify the response options were well received.

Conclusion

The qualitative data from individuals with CLBP confirmed that the RMDQ has content validity and, alongside documented psychometric evidence, supports the use of the RMDQ as a reliable and valid tool to assess the impact of CLBP on physical functioning.
Exploring the influence of socio-cultural factors and environmental resources on the health related quality of life of children and adolescents after congenital heart disease surgery: parental perspectives from a low middle income country
Authors: Ladak Laila A. , Gallagher Robyn , Hasan Babar S. , Awais Khadija , Abdullah Ahmed , Gullick Janice
Published: August 2020

Background

Health related quality of life (HRQOL) is an important indicator of long-term well-being, influenced by environmental factors such as family, culture, societal norms and available resources. This study aimed to explore parental perspectives on the influence of socio-cultural factors and environmental resources on the HRQOL of children and adolescents after congenital heart disease (CHD) surgery.

Methods

Using a descriptive, qualitative design, semi-structured interviews of children/adolescents who had CHD surgery in this low-middle income country (LMIC) were collected between July to December 2017. There were 20 families enrolled, which included 18 parent dyads (mother and father) and two single mothers, making a total of 38 participants. Initial inductive analysis was further refined using the Social Ecological Model as an analytic lens.

Results

At the intrapersonal level, unrealistic expectations of surgery, residual CHD symptoms and difficulty maintaining educational progress were of great concern. There were low levels of health literacy and understanding about CHD among family and friends, however, strong kinship ties were an important resource at the interpersonal level. These families lived in poverty and mothers often carried the sole burden of care for their sick children. At the institutional level, there were unclear expectations of the child’s needs at school, and parents had poor access to psychological, family-planning and genetic counselling, and poor access to CHD education resources. At a sociocultural level, religion and trust in God were important coping factors, however, CHD was a gendered experience with particular concerns around scarring and the marriageability of girls. Parents noted the deficit of antenatal and specialist CHD services and felt the consequence of a lack of a universal health care system at the public policy level.

Conclusion

Socio-ecological factors have the potential to explain the issues and challenges that children living in LMIC experience with CHD after surgery. The study findings will help to inform future interventions to be implemented in countries like Pakistan.
A cervical tuberculous abscess mimicking a fourth branchial cleft cyst in a child: PCR, the key to fast diagnosis
Authors: Riahi Inès , Fradi Rim , Jaafoura Habib , Kanzari Lamia
Published: August 2020

Background

Anterior cervical tuberculous abscess is a rare presentation of extrapulmonary tuberculosis even in endemic countries.

Case presentation

We report a case of a 14-year-old girl with a 5 day history of an anterior mass. The diagnosis of an infected fourth branchial cleft cyst was first evoked. Fine-needle aspiration cytology was suggestive of tuberculosis. Polymerase chain reaction analysis was the key to the diagnosis of a tuberculous abscess.

Conclusions

In endemic countries, abscesses occurring in uncommon sites should be dealt with a high degree of suspicion for tuberculosis. Early diagnosis is essential to initiate specific and effective treatment. Pre-operative diagnosis avoids invasive surgery and related complications.