bluuebunny/crossref_metadata_2025 huggingface dataset:
Massive Bilateral Hydroureteronephrosis and End-Stage Renal Disease Ensuing From Chronic Schistosomiasis: A Case Report
Authors: Pallangyo Pedro , Bhalia Smita , Simelane Nontobeko Nokulunga , Lyimo Frederick , Swai Happiness Judical , Mkojera Zabella Seifu , Hemed Naairah Rashid , Misidai Nsajigwa , Millinga Jalack , Janabi Mohamed
Published: March 2020

Globally, schistosomal infections affect over 200 million people resulting in the loss of 70 million disability-adjusted life years. In the sub-Saharan Africa region, where over 85% of the global schistosomal infections are found, it is estimated that about 120 million people become symptomatic, over 20 million have severe disease, and nearly 200 000 die every year. Renal impairment is a severe consequence of schistosomiasis occurring in about 6% of all infected individuals and in 15% of those with the hepatosplenic form. We present a case of massive bilateral hydroureteronephrosis and end-stage renal disease resulting from chronic schistosomiasis in a 38-year-old male of African origin. A 38-year-old male rice farmer of African origin presented with a history of elevated blood pressure, abdominal swelling, and reduced urinary output for about 10 months. Abdominal examination revealed an intraabdominal mass measuring 30 cm × 17 cm extending from the right hypochrondrium region downward to right inguinal outward to umbilicus crossing the midline. He had an estimated glomerular filtration rate of 3.9 mL/min, hemoglobin of 6.78 g/dL, and had multiple electrolyte abnormalities. A computed tomography intravenous urogram scan of the abdomen revealed hepatomegaly (18 cm), bilateral renal enlargement with hydroureteronephrosis, and multiple calcifications on the urinary bladder. A rectal biopsy isolated haematobium eggs and confirmed the diagnosis. Urinary schistosomiasis can have distressing effects on the urinary system in particular and survival prospects in general. In view of this, extensive evaluation of the genitourinary system is pivotal for timely diagnosis and prompt management particularly in residents of schistosoma-endemic communities presenting with obstructive uropathy.
Critical Thinking in Health Sciences and How It Pertains to Sonography Education: A Review of the Literature
Authors: Weidman Brandy , Salisbury Helen
Published: March 2020

Objective:

Critical thinking is an important skill that sonographers must develop beginning in educational programs and into professional practice. Critical thinking requires students to reflect on information, use judgment skills, and engage in higher levels of thinking, including analysis, interpretation, inference, evaluation, and explanation, to formulate reliable decisions.

Methods:

Current research related to critical thinking has focused on medicine, nursing, physical therapy, pharmacy, and dental programs, but there has been no description of assessing sonography students. The Dreyfus model has been used as a framework to describe acquired skills that reflects students’ progress from novice to expert clinicians. This model illustrates specific cognitive abilities that students develop as they advance in education.

Results:

This review of the literature describes critical thinking skills coupled with a framework to understand different levels of cognitive thinking, as well as how it can be assessed.

Conclusion:

To understand differences between undergraduate sonography students and experts, the Dreyfus model is an excellent model to recognize progression. It can be used with the Health Sciences Reasoning Test, which is a nationally recognized critical thinking examination that can ascertain different levels of health sciences students’ critical thinking skills.
Detecting circular RNA from high-throughput sequence data with de Bruijn graph
Authors: Li Xin , Wu Yufeng
Published: March 2020

Background

Circular RNA is a type of non-coding RNA, which has a circular structure. Many circular RNAs are stable and contain exons, but are not translated into proteins. Circular RNA has important functions in gene regulation and plays an important role in some human diseases. Several biological methods, such as RNase R treatment, have been developed to identify circular RNA. Multiple bioinformatics tools have also been developed for circular RNA detection with high-throughput sequence data.

Results

In this paper, we present circDBG, a new method for circular RNA detection with de Bruijn graph. We conduct various experiments to evaluate the performance of CircDBG based on both simulated and real data. Our results show that CircDBG finds more reliable circRNA with low bias, has more efficiency in running time, and performs better in balancing accuracy and sensitivity than existing methods. As a byproduct, we also introduce a new method to classify circular RNAs based on reads alignment. Finally, we report a potential chimeric circular RNA that is found by CircDBG based on real sequence data. CircDBG can be downloaded from https://github.com/lxwgcool/CircDBG.

Conclusions

We develop a new method called CircDBG for circular RNA detection, which is based on de Bruijn graph. We conduct extensive experiments and demonstrate CircDBG outperforms existing tools, especially in saving running time, reducing bias and improving capability of balancing accuracy and sensitivity. We also introduce a new method to classify circular RNAs and report a potential case of chimeric circular RNA.
InvBFM: finding genomic inversions from high-throughput sequence data based on feature mining
Authors: Wu Zhongjia , Wu Yufeng , Gao Jingyang
Published: March 2020

Background

Genomic inversion is one type of structural variations (SVs) and is known to play an important biological role. An established problem in sequence data analysis is calling inversions from high-throughput sequence data. It is more difficult to detect inversions because they are surrounded by duplication or other types of SVs in the inversion areas. Existing inversion detection tools are mainly based on three approaches: paired-end reads, split-mapped reads, and assembly. However, existing tools suffer from unsatisfying precision or sensitivity (eg: only 50~60% sensitivity) and it needs to be improved.

Result

In this paper, we present a new inversion calling method called InvBFM. InvBFM calls inversions based on feature mining. InvBFM first gathers the results of existing inversion detection tools as candidates for inversions. It then extracts features from the inversions. Finally, it calls the true inversions by a trained support vector machine (SVM) classifier.

Conclusions

Our results on real sequence data from the 1000 Genomes Project show that by combining feature mining and a machine learning model, InvBFM outperforms existing tools. InvBFM is written in Python and Shell and is available for download at https://github.com/wzj1234/InvBFM.
Terlipressin for the treatment of septic shock in adults: a systematic review and meta-analysis
Authors: Huang Lili , Zhang Shi , Chang Wei , Xia Feiping , Liu Songqiao , Yang Yi , Qiu Haibo
Published: March 2020

Background

Catecholamines are the first-line vasopressors used in patients with septic shock. However, the search for novel drug candidates is still of great importance due to the development of adrenergic hyposensitivity accompanied by a decrease in catecholamine activity. Terlipressin (TP) is a synthetic vasopressin analogue used in the management of patients with septic shock. In the current study, we aimed to compare the effects of TP and catecholamine infusion in treating septic shock patients.

Methods

A systematic review and meta-analysis was conducted by searching articles published in PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials between inception and July 2018. We only selected randomized controlled trials evaluating the use of TP and catecholamine in adult patients with septic shock. The primary outcome was overall mortality. The secondary outcomes were the ICU length of stay, haemodynamic changes, tissue perfusion, renal function, and adverse events.

Results

A total of 9 studies with 850 participants were included in the analysis. Overall, no significant difference in mortality was observed between the TP and catecholamine groups (risk ratio(RR), 0.85 (0.70 to 1.03); P = 0.09). In patients < 60 years old, the mortality rate was lower in the TP group than in the catecholamine group (RR, 0.66 (0.50 to 0.86); P = 0.002). There was no significant difference in the ICU length of stay (mean difference, MD), − 0.28 days; 95% confidence interval (CI), − 1.25 to 0.69; P = 0.58). Additionally, TP improved renal function. The creatinine level was decreased in patients who received TP therapy compared to catecholamine-treated participants (standard mean difference, SMD), − 0.65; 95% CI, − 1.09 to − 0.22; P = 0.003). No significant difference was found regarding the total adverse events (Odds Ratio(OR), 1.48(0.51 to 4.24); P = 0.47), whereas peripheral ischaemia was more common in the TP group (OR, 8.65(1.48 to 50.59); P = 0.02).

Conclusion

The use of TP was associated with reduced mortality in septic shock patients less than 60 years old. TP may also improve renal function and cause more peripheral ischaemia. PROSPERO registry: CRD42016035872.
Efficacy and safety of standard and low dose ticagrelor versus clopidogrel in east AsianPatients with chronic total occlusion undergoing percutaneous coronary intervention: a single center retrospective study
Authors: Wang Yong , Zhao Hong-wei , Wang Cheng-fu , Zhang Xiao-jiao , Tao Jie , Cui Chun-sheng , Meng Qing-kun , Zhu Yu , Luo De-feng , Hou Ai-jie , Luan Bo
Published: March 2020

Background

Patients with coronary chronic total occlusion (CTO) require effective antiplatelet therapy after percutaneous coronary intervention (PCI). Ticagrelor has more pronounced platelet inhibition than clopidogrel. However, the most appropriate dose of ticagrelor in East Asian populations remains unclear.

Method

We compared ticagrelor (180 mg loading dose, 90 mg twice daily thereafter and 120 mg loading dose, 60 mg twice daily thereafter) and clopidogrel (300 mg loading dose, 75 mg daily thereafter) for prevention of cardiovascular events in 525patients with CTO undergoing PCI.

Results

The rate of in-hospital major adverse cardiac and cerebral events (MACCE) was not different between the groups. At 1-year follow-up, target vessel revascularization (TVR) in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.047); TVR was significantly decreased in 60 mg ticagrelor compared to standard dose clopidogrel (p = 0.046). At 1-year follow-up, overall MACCE in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.023). Kaplan–Meier analysis showed MACCE-free survival was significantly higher in both ticagrelor groups than in the clopidogrel group (p = 0.024). During hospitalization, minor bleeding was significant increased in the 90 mg ticagrelor group (p = 0.021). At 1-year follow-up, risk of major and minor bleeding were significantly increased in the 90 mg ticagrelor group.

Conclusion

In East Asian patients with CTO undergoing PCI, 60 mg ticagrelor was as effective as 90 mg, at the same time significantly reduced risk of bleeding.
Evaluation of the accuracy of two point-of-care haemoglobin meters used in sub-Saharan African population: a cross-sectional study
Authors: Choukem Simeon-Pierre , Sih Colette , Ntumsi Akondu Tontu , Dimala Christian Akem , Mboue-Djieka Yannick , Ngouadjeu Eveline D. T. , Kengne Andre-Pascal
Published: March 2020

Background

Point-of-care haemoglobin meters are attractive solutions to improve timely diagnosis of anaemia in resource-limited settings. However, concerns regarding the accuracy of these meters may affect their adoption. The accuracy of two hand-held point-of-care haemoglobin meters was evaluated against reference full blood count analyser.

Methods

This was a hospital-based cross-sectional study conducted at the Douala General hospital, Cameroon. Two handheld haemoglobin meters were assessed: Urit12® (URIT Medical Electronics Co.,Ltd. Guangxi, China) and MissionHb®(ACON Laboratories, Inc., San Diego, USA); against a reference standard CELL-DYN RUBY® (ABBOTT DIAGNOSTICS, Illinois, USA). The Pearson’s correlation and Bland-Altman agreement were used to assess the technical accuracy of the meters. Clinical accuracy was evaluated using total error allowable and area under the Receiver Operating Curve. Finally, their agreement with the reference in diagnosing anaemia was assessed using the kappa statistic.

Results

A total of 228 participants were included in the study. The mean haemoglobin values of both haemoglobin meters (MissionHb®: 11.6 ± 2.5 g/dl; Urit12®: 10.9 ± 2.7 g/dl) were significantly higher than the reference value (10.5 ± 2.5 g/dl), p < 0.001 for both meters. Both haemoglobin meters had good correlation with the reference analyser (r = 0.89 and r = 0.90 for Urit12® and MissionHb® respectively) and good agreement on the Bland-Altman plots. However, the MissionHb® meter did not meet the clinical accuracy requirements (p < 0.001). Even though both meters were excellent at identifying the presence of anemia (MissionHb® - AUC = 0.9161, Urit 12® - AUC = 0.9009), they, however, both had weak agreement with the reference analyser in diagnosing the severity of anaemia (K = 0.39 for MissionHb®, p < 0.001 and K = 0.54 for Urit12®, p < 0.001).

Conclusion

Although both devices showed technical accuracy with a positive correlation with the reference analyser and were able to accurately diagnose the presence of anemia, both meters however, had sub-optimal agreement with the reference analyser in diagnosing the degree of severity of anaemia among our participants.
Different adiposity indices and their associations with hypertension among Chinese population from Jiangxi province
Authors: Hu Lihua , Hu Guiping , Huang Xiao , Zhou Wei , You Chunjiao , Li Juxiang , Li Ping , Wu Yanqing , Wu Qinghua , Wang Zengwu , Gao Runlin , Bao Huihui , Cheng Xiaoshu
Published: March 2020

Background

To date, the best adiposity index that predicts or associates strongly with hypertension remains controversial. Therefore, we aimed to compare the performance of different adiposity indices [BMI (body mass index), WC (waist circumference), WHtR (waist-to-height ratio), ABSI (a body shape index), VAI (visceral adipose index), BFP (body fat percentage)] as associates and potential predictors of risk of hypertension among Chinese population.

Methods

A cross-sectional survey was conducted in Jiangxi province, China from 2013 to 2014. A total of 14,573 participants were included in the study. The physical measurements included body height, weight, WC, BFP and VAI. Multivariate logistic regression analysis was performed to assess the associations between different adiposity indices and the prevalence of hypertension. Receiver operating characteristic (ROC) analysis was also performed.

Results

All adiposity indices were independently and positively associated with the prevalence of hypertension in a dose response fashion. The area under the curves (AUCs) for WHtR, BFP and VAI were significantly larger than those for other adiposity indices in both males and females (all P < 0.01). For males, no statistically significant difference was found in AUCs among WHtR and BFP (0.653 vs. 0.647, P = 0.4774). The AUC of WHtR was significantly higher than VAI (0.653 vs. 0.636, P < 0.01). For females, the AUCs demonstrated that WHtR was significantly more powerful than BFP and VAI (both P < 0.05) for predicting hypertension [WHtR, 0.689 (0.677–0.702); BFP, 0.677 (0.664–0.690); VAI, 0.668 (0.655–0.680)]. Whereas no significant differences were found in AUCs for hypertension among BFP and VAI in both sexes (all P > 0.1). The AUCs for hypertension associated with each adiposity index declined with age in both males and females. For subjects aged < 65 years, WHtR still had the largest AUC. However, for participants aged ≥65 years, BMI had the largest AUC.

Conclusion

The findings indicated that WHtR was the best for predicting hypertension, followed by BFP and VAI, especially in younger population.
Impaired fasting glucose and major adverse cardiovascular events by hypertension and dyslipidemia status: the Golestan cohort study
Authors: Hashemi Madani Nahid , Ismail-Beigi Faramarz , Poustchi Hossein , Nalini Mahdi , Sepanlou Sadaf G. , Malek Mojtaba , Abbasi Mohammad Amin , Khajavi Alireza , Khamseh Mohammad E. , Malekzadeh Reza
Published: March 2020

Background

Whether pre-diabetes in the absence of hypertension (HTN) or dyslipidemia (DLP) is a risk factor for occurrence of major adverse cardiovascular events (MACE) is not fully established. We investigated the effect of impaired fasting glucose (IFG) alone and in combination with HTN, DLP or both on subsequent occurrence of MACE as well as individual MACE components.

Methods

This longitudinal population-based study included 11,374 inhabitants of Northeastern Iran. The participants were free of any cardiovascular disease at baseline and were followed yearly from 2010 to 2017. Cox proportional hazard models were fitted to measure the hazard of IFG alone or in combination with HTN and DLP on occurrence of MACE as the primary endpoint.

Results

Four hundred thirty-seven MACE were recorded during 6.2 ± 0.1 years follow up. IFG alone compared to normal fasting glucose (NFG) was not associated with an increase in occurrence of MACE (HR, 0.87; 95% CI, 0.19–4.02; p, 0.854). However, combination of IFG and HTN (HR, 2.88; 95% CI, 2.04–4.07; p, 0.000) or HTN + DLP (HR, 2.98; 95% CI, 1.89–4.71; p, 0.000) significantly increased the risk for MACE. Moreover, IFG + DM with or without HTN, DLP, or both was also associated with an increase in the incidence of MACE.

Conclusion

IFG, per se, does not appear to increase hazard of MACE. However, IFG with HTN or HTN + DLP conferred a significant hazard for MACE in an incremental manner. Moreover, IFG without HTN, adjusted for DLP, can be associated with an increase in the risk for CVD- death.
Real-world effectiveness and safety of sofosbuvir and nonstructural protein 5A inhibitors for chronic hepatitis C genotype 1, 2, 3, 4, or 6: a multicentre cohort study
Authors:   The THASL Collaborating Group for the Study of the Use of Direct-acting Antivirals for Chronic Hepatitis C, Charatcharoenwitthaya Phunchai , Wongpaitoon Virasak , Komolmit Piyawat , Sukeepaisarnjaroen Wattana , Tangkijvanich Pisit , Piratvisuth Teerha , Sanpajit Theeranun , Sutthivana Chinnavat , Bunchorntavakul Chalermrat , Sobhonslidsuk Abhasnee , Chonprasertsuk Soonthorn , Siripipattanamongkol Chotipong , Sethasine Supatsri , Tanwandee Tawesak
Published: March 2020

Background

We investigated real-world effectiveness and safety of sofosbuvir and the nonstructural protein 5A inhibitors in the treatment of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, 4, or 6.

Methods

We analyzed data from 1021 patients with HCV infection (506 with genotype 1; 16 with genotype 2; 314 with genotype 3; 13 with genotype 4; 166 with genotype 6) who received 12 to 24 weeks of daclatasvir plus sofosbuvir (n = 767), ledipasvir/sofosbuvir (n = 197), or sofosbuvir/velpatasvir (n = 57), with or without ribavirin in 12 centers across Thailand to estimate sustained virologic response at post-treatment week 12 (SVR12).

Results

Overall, SVR12 rate was 98.0% (95% confidence interval [CI], 96.7–98.8%) with daclatasvir plus sofosbuvir, 97.9% (95% CI, 94.8–99.2%) with ledipasvir/sofosbuvir, and 96.5% (95% CI, 88.1–99.0%) with sofosbuvir/velpatasvir. SVR12 was achieved by 99.2% (95% CI, 97.9–99.7%) of subjects with genotype 1 infection, 100% (95% CI, 78.5–100%) of those with genotype 2 infection, 96.7% (95% CI, 94.0–98.2%) of those with genotype 3 infection, 90.9% (95% CI, 62.3–98.4%) of those with genotype 4 infection, and 96.7% (95% CI 92.5–98.6%) of those with genotype 6 infection. Patients with advanced liver disease were at risk of treatment failure. Only four patients discontinued treatment before week 4 due to non-hepatic adverse events.

Conclusions

In this large cohort of patients with various HCV genotypes managed in the real-world practice setting, daclatasvir plus sofosbuvir, ledipasvir/sofosbuvir, and sofosbuvir/velpatasvir achieved high SVR rates with good safety profile, comparable to those observed in clinical trials.
The paradox of aging and health-related quality of life in Asian Chinese: results from the Healthy Aging Longitudinal Study in Taiwan
Authors: Tseng Han-Yun , Löckenhoff Corinna , Lee Chun-Yi , Yu Shu-Han , Wu I-Chien , Chang Hsing-Yi , Chiu Yen-Feng , Hsiung Chao Agnes
Published: March 2020

Background

Declines in health, physical, cognitive, and mental function with age suggest a lower level of health-related quality of life (HRQoL) in late life; however, previous studies found that the associations were weak and varied, depending on the study designs and cohort characteristics.

Methods

The present study examined the paradox of aging in an East Asian context by regressing the age patterns of objective health indicators (physical, cognitive, and mental function), and subjective HRQoL (12-item Short Form, SF-12), on the independent and interactive effects of age and physical function in a cohort study of 5022 community-dwelling adults aged 55 and older in Taiwan.

Results

Age patterns differed across measures. The SF-12 mental health score (MCS) showed a slight positive association with age and this effect remained stable after controlling for various age-related covariates. The SF-12 physical health score (PCS), in turn, was negatively associated with age. Age differences in PCS were fully explained by age decrements in objective physical health. However, consistent with the so-called paradox of aging, the association between objective and subjective physical health weakened with age.

Conclusion

These findings add to prior evidence indicating that — in spite of objective health decrements — subjective HRQoL is maintained in later life among Asian Chinese. Also, these paradoxical patterns appear to vary for mental and physical components of HRQoL, and future research is needed to explore the underlying mechanism.

Trial registration

Healthy Aging Longitudinal Study in Taiwan (HALST) is retrospectively registered at ClinicalTrials.gov on January 24, 2016 with trial registration number NCT02677831.
A comparative study on the validations of three cognitive screening tests in identifying subtle cognitive decline
Authors: Pan Feng-Feng , Huang Lin , Chen Ke-liang , Zhao Qian-hua , Guo Qi-hao
Published: March 2020

Background

Subtle cognitive decline (SCD) may represent a very early stage of objective cognitive impairment before mild cognitive impairment (MCI), with less neuronal damage and more functional reservation. Detecting individuals with SCD is imperative for dementia prevention and treatment. In this study, we aimed to compare the validations of three cognitive screening tests, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment-Chinese Version (MoCA-CV), and Memory and Executive Screening (MES), in identifying subtle cognitive decline.

Methods

A total of 407 individuals were recruited, including 147 cognitively normal controls (NC), 102 individuals with subtle cognitive decline (SCD) and 158 individuals with mild cognitive impairment (MCI) according to the operational neuropsychological criteria proposed by Jak and Bondi’s. All participants underwent standardized comprehensive neuropsychological tests and the three cognitive screening tests. Chi-square analysis was used to compare the cognitive performance among the groups of NC, SCD and MCI. Receiver operating characteristic (ROC) curves were used to evaluate the abilities of MMSE, MoCA-CV and MES in discriminating NC, SCD and MCI.

Results

Compared with NC, SCD showed a significant decline only in the tests of memory, such as Auditory Verbal Learning Test (AVLT), Rey-Osterrieth Complex Figure Test (CFT) and Prospective Memory Test (PrM) (P < 0.01). However, MCI showed significant decline in all cognitive performances (P < 0.01). The scores of MMSE, MoCA-CV and MES all showed a progressive downward trend within the groups of NC, SCD and MCI (P < 0.001). In ROC Analyses for discriminating individuals with SCD from NC, the most appropriate MES cutoff was 84, with a sensitivity of 74.3%, a specificity of 60.8% and 0.738 for AUC (95%CI, 0.675–0.801). By contrast, MMSE and MOCA-CV had poor sensitivity (67.4 and 70.8%, respectively) and specificity (51.0 and 52.9%, respectively), and smaller AUCs (0.643 and 0.644, respectively) than the MES.

Conclusion

As a screening test, MES is more efficacious in identifying SCD from normal controls than MMSE and MoCA-CV.
Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study
Authors: Zhu Lin , Hayen Andrew , Bell Katy J. L.
Published: March 2020

Background

The Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Lipid study found no evidence of a beneficial effect of statin-fibrate combined treatment, compared to statins alone, on cardiovascular outcomes and mortality in type 2 diabetes mellitus after 5 years of active treatment. However, a beneficial reduction in major CVD events was shown in a pre-specified sub-group of participants with dyslipidemia. The extended follow-up of this trial provides the opportunity to further investigate possible beneficial effects of fibrates in this group of patients. We aimed to evaluate possible “legacy effects” of fibrate add-on therapy on mortality and major cardiovascular outcomes in patients with dyslipidemia.

Methods

The ACCORD-lipid study was a randomized controlled trial of 5518 participants assigned to receive simvastatin plus fenofibrate vs simvastatin plus placebo. After randomized treatment allocation had finished at the end of the trial, all surviving participants were invited to attend an extended follow-up study (ACCORDION) to continue prospective collection of clinical outcomes. We undertook a secondary analysis of trial and post-trial data in patients who had dyslipidemia. The primary outcome was all-cause and cardiovascular mortality, and secondary outcomes were nonfatal myocardial infarction, stroke, congestive heart failure and major coronary heart disease. We used an intention-to-treat approach to analysis to make comparisons between the original randomized treatment groups.

Results

853 participants with dyslipidemia had survived at the end of the trial. Most participants continued to use statins, but few used fibrates in either group during the post-trial period. The incidence rates in the fenofibrate group were lower with respect to all-cause mortality, CVD mortality, nonfatal myocardial infarction, congestive heart failure and major coronary heart disease than those in the placebo group over a post-trial follow-up. Allocation to the combined fibrate-statin treatment arm during the trial period had a beneficial legacy effect on all-cause mortality (adjusted HR = 0.65, 95% CI 0.45–0.94; P = 0.02).

Conclusions

Fibrate treatment during the initial trial period was associated with a legacy benefit of improved survival over a post-trial follow-up. These findings support re-evaluation of fibrates as an add-on strategy to statins in order to reduce cardiovascular risk in diabetic patients with dyslipidemia.

Trial registration clinicaltrials.gov, Identifier: NCT00000620
Health related quality of life associated with extreme obesity in adolescents – results from the baseline evaluation of the YES-study
Authors: Felix J. , Stark R. , Teuner C. , Leidl R. , Lennerz B. , Brandt S. , von Schnurbein J. , Moss A. , Bollow E. , Sergeyev E. , Mühlig Y. , Wiegand S. , Holl R. W. , Reinehr T. , Kiess W. , Scherag A. , Hebebrand J. , Wabitsch M. , Holle R.
Published: March 2020

Background

Obesity can significantly reduce health-related quality of life (HRQoL) and may lead to numerous health problems even in youths. This study aimed to investigate whether HRQoL varies among youths with obesity depending on grade of obesity and other factors.

Methods

For the Youths with Extreme obesity Study (YES) (2012–2014), a prospective multicenter cohort study, a baseline sample of 431 obese and extremely obese adolescents and young adults (age 14 to 24 years, BMI ≥30 kg/m2) was recruited at four German university medical centers and one job center. Obesity grade groups (OGG) were defined according to BMI (OGG I: 30–34.9 kg/m2, OGG II: 35–39.9 kg/m2, OGG III (extreme obesity): ≥40 kg/m2). HRQoL was measured with the Euroqol-5D-3 L (EQ-5D-3 L), DISABKIDS chronic generic (DCGM-31) and the KINDLR obesity module. Differences between OGGs were assessed with logistic and linear regression models, adjusting for age, sex, and study center in the base model. In a second regression analysis, we included other characteristics to identify possible determinants of HRQoL.

Results

Three hundred fifty-two adolescents (mean age: 16.6 (±2.4), mean BMI: 39.1 (±7.5) kg/ m2) with available HRQoL data were analysed. HRQoL of youths in all OGGs was markedly lower than reference values of non-obese adolescents. Adjusting for age and sex, HRQoL of youths in OGG III significantly impaired compared to OGG I. Youths in OGG III were 2.15 times more likely to report problems with mobility in the EQ-5D-3 L than youths in OGG I. A mean difference of 9.7 and 6.6 points between OGG III and I were found for DCGM-31 and KINDL respectively and 5.1 points between OGG II and I for DCGM-31. Including further variables into the regression models, showed that HRQoL measured by DCGM-31 was significantly different between OGGs. Otherwise, female sex and having more than 4 h of daily screen time were also associated with lower HRQoL measured by DCGM-31 and KINDL.

Conclusion

HRQoL of adolescents with obesity is reduced, but HRQoL of adolescents with extreme obesity is particularly affected. Larger and longitudinal studies are necessary to understand the relation of extreme obesity and HRQoL, and the impact of other lifestyle or socioeconomic factors.

Trial Registration

Clinicaltrials.gov NCT01625325; German Clinical Trials Register (DRKS) DRKS00004172.
HIV drug resistance in patients in China’s national HIV treatment programme who have been on first-line ART for at least 9 months
Authors: Liu Pengtao , Xing Hui , Liao Lingjie , Feng Yi , Leng Xuebing , Wang Jing , Kan Wei , Yan Jing , Li Yang , Zuo Zhongbao , You Yinghui , Ruan Yuhua , Shao Yiming
Published: March 2020

Background

The aim of this study was to assess trends in drug resistance and associated clinical and programmatic factors at a national level during the rapid scale up of ART.

Methods

Logistic regression was used to identify the factors associated with HIVDR. Variables associated with drug resistance in multivariable logistic regression were included in the Cochran–Armitage test for trend.

Results

A total of 11,976 patients were enrolled in the study. The prevalence of HIVDR among patients who received ART for 9–24 months during 2003–2008, 2009–2012, and 2013–2015 significantly decreased (15.5%, 6.3%, and 2.3%, respectively,P < 0.01). With respect to the class of antiretroviral, there were substantial increases in resistance to both non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) (2003–2008, 2009–2012, and 2013–2015: 49.7%, 58.9%, and 73.0%, respectively,P < 0.01). The prevalence of DR to protease inhibitors (PIs) was low, which supported their continued use as second-line therapy in China.

Conclusions

Our results provide evidence for the effectiveness of China’s “Treat All” approach to guide policy makers to improve training for healthcare providers and education on ART adherence among patients.
The pivotal role of micro-environmental cells in a human blood–brain barrier in vitro model of cerebral ischemia: functional and transcriptomic analysis
Authors: Gerhartl Anna , Pracser Nadja , Vladetic Alexandra , Hendrikx Sabrina , Friedl Heinz-Peter , Neuhaus Winfried
Published: March 2020

Background

The blood–brain barrier (BBB) is altered in several diseases of the central nervous system. For example, the breakdown of the BBB during cerebral ischemia in stroke or traumatic brain injury is a hallmark of the diseases’ progression. This functional damage is one key event which is attempted to be mimicked in in vitro models. Recent studies showed the pivotal role of micro-environmental cells such as astrocytes for this barrier damage in mouse stroke in vitro models. The aim of this study was to evaluate the role of micro-environmental cells for the functional, paracellular breakdown in a human BBB cerebral ischemia in vitro model accompanied by a transcriptional analysis.

Methods

Transwell models with human brain endothelial cell line hCMEC/D3 in mono-culture or co-culture with human primary astrocytes and pericytes or rat glioma cell line C6 were subjected to oxygen/glucose deprivation (OGD). Changes of transendothelial electrical resistance (TEER) and FITC-dextran 4000 permeability were recorded as measures for paracellular tightness. In addition, qPCR and high-throughput qPCR Barrier chips were applied to investigate the changes of the mRNA expression of 38 relevant, expressed barrier targets (tight junctions, ABC-transporters) by different treatments.

Results

In contrast to the mono-culture, the co-cultivation with human primary astrocytes/pericytes or glioma C6 cells resulted in a significantly increased paracellular permeability after 5 h OGD. This indicated the pivotal role of micro-environmental cells for BBB breakdown in the human model. Hierarchical cluster analysis of qPCR data revealed differently, but also commonly regulated clustered targets dependent on medium exchange, serum reduction, hydrocortisone addition and co-cultivations.

Conclusions

The co-cultivation with micro-environmental cells is necessary to achieve a functional breakdown of the BBB in the cerebral ischemia model within an in vivo relevant time window. Comprehensive studies by qPCR revealed that distinct expression clusters of barrier markers exist and that these are regulated by different treatments (even by growth medium change) indicating that controls for single cell culture manipulation steps are crucial to understand the observed effects properly.
A novel extramedullary technique to guide femoral bone preparation in mobile unicompartmental knee arthroplasty based on tibial cut and overall alignment
Authors: Zhang Qidong , Wang Weiguo , Liu Zhaohui , Yue Debo , Cheng Liming , Wang Bailiang , Guo Wanshou
Published: March 2020

Background

The mobile Oxford unicompartmental knee arthroplasty (UKA) implant has been widely used with an intramedullary guide for femoral preparation. We modified the femoral guide technique based on the tibial cut first and spacer block technique. This study was performed to determine the radiographic accuracy and early clinical outcomes of the extramedullary method.

Methods

We retrospectively evaluated 50 consecutive patients who underwent UKA using the extramedullary technique. An equal number of patients who underwent UKA with the conventional technique were matched as the control group. Clinical outcomes were evaluated in terms of the operating time, blood loss, range of motion, and Hospital for Special Surgery score. Radiographic accuracy was evaluated by the implant position and alignment in the coronal and sagittal planes.

Results

The mean follow-up period was 39.76 ± 5.77 months. There were no differences in the postoperative Hospital for Special Surgery score, range of motion, or hip-knee-ankle angle between the two groups. The operating time in the extramedullary group was shorter than that in the conventional group (54.78 ± 7.95 vs. 59.14 ± 10.91 min, respectively; p = 0.025). The drop in hemoglobin after 3 days was only 12.34 ± 4.98 g/L in the extramedullary group which was less than that in the conventional group (p = 0.001). No significant differences were found in the postoperative coronal and sagittal angles between the two groups. Acceptable radiographic accuracy of the implant alignment and position was achieved in 92% of patients in the extramedullary group and 96% of patients in the conventional group.

Conclusions

The radiographic and clinical results of the extramedullary technique were comparable with those of the conventional technique with the advantage of no intramedullary interruption, less blood loss, a shorter operating time, and more rapid recovery. As the technique depends on the accurate tibial cut and overall alignment, we do not recommend it to surgeons without high volume experiences.

Trial registration

Retrospectively registered

Level of evidence

IV, retrospective study
PARIS induced defects in mitochondrial biogenesis drive dopamine neuron loss under conditions of parkin or PINK1 deficiency
Authors: Pirooznia Sheila K. , Yuan Changqing , Khan Mohammed Repon , Karuppagounder Senthilkumar S. , Wang Luan , Xiong Yulan , Kang Sung Ung , Lee Yunjong , Dawson Valina L. , Dawson Ted M.
Published: March 2020

Background

Mutations in PINK1 and parkin cause autosomal recessive Parkinson’s disease (PD). Evidence placing PINK1 and parkin in common pathways regulating multiple aspects of mitochondrial quality control is burgeoning. However, compelling evidence to causatively link specific PINK1/parkin dependent mitochondrial pathways to dopamine neuron degeneration in PD is lacking. Although PINK1 and parkin are known to regulate mitophagy, emerging data suggest that defects in mitophagy are unlikely to be of pathological relevance. Mitochondrial functions of PINK1 and parkin are also tied to their proteasomal regulation of specific substrates. In this study, we examined how PINK1/parkin mediated regulation of the pathogenic substrate PARIS impacts dopaminergic mitochondrial network homeostasis and neuronal survival in Drosophila.

Methods

The UAS-Gal4 system was employed for cell-type specific expression of the various transgenes. Effects on dopamine neuronal survival and function were assessed by anti-TH immunostaining and negative geotaxis assays. Mitochondrial effects were probed by quantitative analysis of mito-GFP labeled dopaminergic mitochondria, assessment of mitochondrial abundance in dopamine neurons isolated by Fluorescence Activated Cell Sorting (FACS) and qRT-PCR analysis of dopaminergic factors that promote mitochondrial biogenesis. Statistical analyses employed two-tailed Student’s T-test, one-way or two-way ANOVA as required and data considered significant when P < 0.05.

Results

We show that defects in mitochondrial biogenesis drive adult onset progressive loss of dopamine neurons and motor deficits in Drosophila models of PINK1 or parkin insufficiency. Such defects result from PARIS dependent repression of dopaminergic PGC-1α and its downstream transcription factors NRF1 and TFAM that cooperatively promote mitochondrial biogenesis. Dopaminergic accumulation of human or Drosophila PARIS recapitulates these neurodegenerative phenotypes that are effectively reversed by PINK1, parkin or PGC-1α overexpression in vivo. To our knowledge, PARIS is the only co-substrate of PINK1 and parkin to specifically accumulate in the DA neurons and cause neurodegeneration and locomotor defects stemming from disrupted dopamine signaling.

Conclusions

Our findings identify a highly conserved role for PINK1 and parkin in regulating mitochondrial biogenesis and promoting mitochondrial health via the PARIS/ PGC-1α axis. The Drosophila models described here effectively recapitulate the cardinal PD phenotypes and thus will facilitate identification of novel regulators of mitochondrial biogenesis for physiologically relevant therapeutic interventions.
The H2O2-dependent activity of a fungal lytic polysaccharide monooxygenase investigated with a turbidimetric assay
Authors: Filandr Frantisek , Man Petr , Halada Petr , Chang Hucheng , Ludwig Roland , Kracher Daniel
Published: March 2020

Background

Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent redox enzymes that cleave recalcitrant biopolymers such as cellulose, chitin, starch and hemicelluloses. Although LPMOs receive ample interest in industry and academia, their reaction mechanism is not yet fully understood. Recent studies showed that H2O2 is a more efficient cosubstrate for the enzyme than O2, which could greatly affect the utilization of LPMOs in industrial settings.

Results

We probe the reactivity of LPMO9C from the cellulose-degrading fungus Neurospora crassa with a turbidimetric assay using phosphoric acid-swollen cellulose (PASC) as substrate and H2O2 as a cosubstrate. The measurements were also followed by continuous electrochemical H2O2 detection and LPMO reaction products were analysed by mass spectrometry. Different systems for the in situ generation of H2O2 and for the reduction of LPMO’s active-site copper were employed, including glucose oxidase, cellobiose dehydrogenase, and the routinely used reductant ascorbate.

Conclusions

We found for all systems that the supply of H2O2 limited LPMO’s cellulose depolymerization activity, which supports the function of H2O2 as the relevant cosubstrate. The turbidimetric assay allowed rapid determination of LPMO activity on a cellulosic substrate without the need for time-consuming and instrumentally elaborate analysis methods.
Analyses of energy metabolism and stress defence provide insights into Campylobacter concisus growth and pathogenicity
Authors: Yeow Melissa , Liu Fang , Ma Rena , Williams Timothy J. , Riordan Stephen M. , Zhang Li
Published: March 2020

Campylobacter concisus is an emerging enteric pathogen that is associated with inflammatory bowel disease. Previous studies demonstrated that C. concisus is non-saccharolytic and hydrogen gas (H2) is a critical factor for C. concisus growth. In order to understand the molecular basis of the non-saccharolytic and H2-dependent nature of C. concisus growth, in this study we examined the pathways involving energy metabolism and oxidative stress defence in C. concisus. Bioinformatic analysis of C. concisus genomes in comparison with the well-studied enteric pathogen Campylobacter jejuni was performed. This study found that C. concisus lacks a number of key enzymes in glycolysis, including glucokinase and phosphofructokinase, and the oxidative pentose phosphate pathway. C. concisus has an incomplete tricarboxylic acid cycle, with no identifiable succinyl-CoA synthase or fumarate hydratase. C. concisus was inferred to use fewer amino acids and have fewer candidate substrates as electron donors and acceptors compared to C. jejuni. The addition of DMSO or fumarate to media resulted in significantly increased growth of C. concisus in the presence of H2 as an electron donor, demonstrating that both can be used as electron acceptors. Catalase, an essential enzyme for oxidative stress defence in C. jejuni, and various nitrosative stress enzymes, were not found in the C. concisus genome. Overall, C. concisus is inferred to have a non-saccharolytic metabolism in which H2 is central to energy conservation, and a narrow selection of carboxylic acids and amino acids can be utilised as organic substrates. In conclusion, this study provides a molecular basis for the non-saccharolytic and hydrogen-dependent nature of C. concisus energy metabolism pathways, which provides insights into the growth requirements and pathogenicity of this species.
DFT codebook-based hybrid precoding for multiuser mmWave massive MIMO systems
Authors: Huang Yu , Liu Chen , Song Yunchao , Yu Xiaolei
Published: March 2020

In millimeter wave (mmWave) massive MIMO (multiple-input multiple-output) systems, it is difficult to apply conventional digital precoding techniques due to hardware constraints. Fortunately, the hybrid precoding can be utilized to reduce power consumption and high costs. In this paper, a codebook-based hybrid precoding scheme for downlink multiuser mmWave massive MIMO systems is proposed. Our main idea is that the analog and digital precoders are designed separately to maximize the achievable sum rate. In the analog domain, we take the potential multiuser conflict and angular domain of channel matrix into consideration and propose an efficient conflicting-aware (CA) beam-column selection method to obtain a discrete Fourier transform (DFT) codebook-based analog precoder. According to the CA method, all users are classified into two groups, i.e., conflicting users (CUs) and non-conflicting users (NCUs). Different criteria of beam-column selection are applied for the two user groups. Then, zero-forcing (ZF) digital precoder is directly used in the digital domain. Simulation results illustrate that our proposed algorithm which has low complexity achieves satisfactory SR performance, which approaches that of the full digital precoding (the upper bound) and outperforms other existing hybrid algorithms.
Analysis of a time-delayed free boundary problem for solid tumor growth with angiogenesis and direct influence of inhibitors
Authors: Xu Shihe , Su Dan
Published: March 2020

In this paper we consider a free boundary problem for tumor growth under direct effect of inhibitors with angiogenesis and time delays in proliferation. The existence and uniqueness of the steady state solution is studied. The asymptotic behavior of steady state solution is proved, and the condition under which the tumor will tend to disappear is given. Finally, we also discuss the effects of the concentration of external inhibitors, the concentration of external nutrients, and the consumption rate of nutrients and inhibitors on the growth of tumors. The results show that under certain conditions the tumor will eventually disappear or will tend to a steady state. The increase of inhibitor concentration (or consumption rate) will lead to the reduction of the radius of the tumor, and the increase of nutrient concentration (or consumption rate) will lead to the increase of the radius of the tumor.
Stability of Ulam–Hyers and Ulam–Hyers–Rassias for a class of fractional differential equations
Authors: Dai Qun , Gao Ruimei , Li Zhe , Wang Changjia
Published: March 2020

In this paper, we investigate a class of nonlinear fractional differential equations with integral boundary condition. By means of Krasnosel’skiĭ fixed point theorem and contraction mapping principle we prove the existence and uniqueness of solutions for a nonlinear system. By means of Bielecki-type metric and the Banach fixed point theorem we investigate the Ulam–Hyers and Ulam–Hyers–Rassias stability of nonlinear fractional differential equations. Besides, we discuss an example for illustration of the main work.