bluuebunny/crossref_metadata_2025 huggingface dataset:
Methodological tools and sensitivity analysis for assessing quality or risk of bias used in systematic reviews published in the high-impact anesthesiology journals
Authors: Marušić Marija Franka , Fidahić Mahir , Cepeha Cristina Mihaela , Farcaș Loredana Gabriela , Tseke Alexandra , Puljak Livia
Published: May 2020

Background

A crucial element in the systematic review (SR) methodology is the appraisal of included primary studies, using tools for assessment of methodological quality or risk of bias (RoB). SR authors can conduct sensitivity analyses to explore whether their results are sensitive to exclusion of low quality studies or a high RoB. However, it is unknown which tools do SR authors use for assessing quality/RoB, and how they set threshold for quality/RoB in sensitivity analyses. The aim of this study was to assess quality/RoB assessment tools, the types of sensitivity analyses and quality/RoB thresholds for sensitivity analyses used within SRs published in high-impact pain/anesthesiology journals.

Methods

This was a methodological study. We analyzed SRs published from January 2005 to June 2018 in the 25% highest-ranking journals within the Journal Citation Reports (JCR) “Anesthesiology” category. We retrieved the SRs from PubMed. Two authors independently screened records, full texts, and extracted data on quality/RoB tools and sensitivity analyses. We extracted data about quality/RoB tools, types of sensitivity analyses and the thresholds for quality/RoB used in them.

Results

Out of 678 analyzed SRs, 513 (76%) reported the use of quality/RoB assessments. The most commonly reported tools for assessing quality/RoB in the studies were the Cochrane tool for risk of bias assessment (N = 251; 37%) and Jadad scale (N = 99; 15%). Meta-analysis was conducted in 451 (66%) of SRs and sensitivity analysis in 219/451 (49%). Most commonly, sensitivity analysis was conducted to explore the influence of study quality/RoB (90/219; 41%) on the results. Quality/RoB thresholds used for sensitivity analysis for those studies were clearly reported in 47 (52%) articles that used them. The quality/RoB thresholds used for sensitivity analyses were highly heterogeneous and inconsistent, even when the same tool was used.

Conclusions

A quarter of SRs reported using quality/RoB assessments, and some of them cited tools that are not meant for assessing quality/RoB. Authors who use quality/RoB to explore the robustness of their results in meta-analyses use highly heterogeneous quality/RoB thresholds in sensitivity analyses. Better methodological consistency for quality/RoB sensitivity analyses is needed.
Effects of parathyroid hormone and vitamin D supplementation on stroke among patients receiving peritoneal dialysis
Authors: You Xiaohan , Zhou Ying , Zhang Jianna , Zhou Qiongxiu , Shi Yanling , Su Zhen , Chen Chaoshen , Shao Rongrong , Zhang Ji
Published: May 2020

Background

Continuous ambulatory peritoneal dialysis (CAPD) patients have a high incidence of stroke and commonly have increased parathyroid hormone levels and vitamin D insufficiency. We seek to investigate the incidence of stroke and the role of parathyroid hormone and vitamin D supplementation in stroke risk among CAPD patients.

Methods

This study employed a retrospective design. We enrolled a Chinese cohort of 980 CAPD patients who were routinely followed in our department. The demographic and clinical data were recorded at the time of initial CAPD and during follow-up. The included patients were separated into non-stroke and stroke groups. The effects of parathyroid hormone and vitamin D supplementation on stroke in CAPD patients was evaluated. The primary endpoint is defined as the first occurrence of stroke, and composite endpoint events are defined as death or switch to hemodialysis during follow-up.

Results

A total of 757 eligible CAPD patients with a mean follow-up time of 54.7 (standard deviation, 33) months were included in the study. The median incidence of stroke among our CAPD patients was 18.9 (interquartile range, 15.7–22.1) per 1000 person-years. A significant nonlinear correlation between baseline iPTH and hazard of stroke (p-value of linear association = 0.2 and nonlinear association = 0.002) was observed in our univariate Cox regression analysis, and low baseline iPTH levels (≤150 pg/ml) were associated with an increased cumulative hazard of stroke. Multivariate Cox regression analysis indicated a significant interaction effect between age and iPTH after adjusting for other confounders. Vitamin D supplementation during follow-up was a predictive factor for stroke in our cohort.

Conclusions

CAPD patients suffered a high risk of stroke, and lower iPTH levels were significantly correlated with an increased risk of stroke. Nevertheless, vitamin D supplementation may reduce the risk of stroke in these patients.
A self-administered, artificial intelligence (AI) platform for cognitive assessment in multiple sclerosis (MS)
Authors: Khaligh-Razavi Seyed-Mahdi , Sadeghi Maryam , Khanbagi Mahdiyeh , Kalafatis Chris , Nabavi Seyed Massood
Published: May 2020

Background

Cognitive impairment is common in patients with multiple sclerosis (MS). Accurate and repeatable measures of cognition have the potential to be used as markers of disease activity.

Methods

We developed a 5-min computerized test to measure cognitive dysfunction in patients with MS. The proposed test – named the Integrated Cognitive Assessment (ICA) – is self-administered and language-independent. Ninety-one MS patients and 83 healthy controls (HC) took part in Substudy 1, in which each participant took the ICA test and the Brief International Cognitive Assessment for MS (BICAMS). We assessed ICA’s test-retest reliability, its correlation with BICAMS, its sensitivity to discriminate patients with MS from the HC group, and its accuracy in detecting cognitive dysfunction. In Substudy 2, we recruited 48 MS patients, 38 of which had received an 8-week physical and cognitive rehabilitation programme and 10 MS patients who did not. We examined the association between the level of serum neurofilament light (NfL) in these patients and their ICA scores and Symbol Digit Modalities Test (SDMT) scores pre- and post-rehabilitation.

Results

The ICA demonstrated excellent test-retest reliability (r = 0.94), with no learning bias, and showed a high level of convergent validity with BICAMS. The ICA was sensitive in discriminating the MS patients from the HC group, and demonstrated high accuracy (AUC = 95%) in discriminating cognitively normal from cognitively impaired participants. Additionally, we found a strong association (r = − 0.79) between ICA score and the level of NfL in MS patients before and after rehabilitation.

Conclusions

The ICA has the potential to be used as a digital marker of cognitive impairment and to monitor response to therapeutic interventions. In comparison to standard cognitive tools for MS, the ICA is shorter in duration, does not show a learning bias, and is independent of language.
Correction to: Obstetric fistulas in Uganda: scoping review using a determinant of health approach to provide a framework for health policy improvement
Authors: den Hollander Geerte C. , Janszen Erica W. M.
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
DPD status and fluoropyrimidines-based treatment: high activity matters too
Authors: Chamorey Emmanuel , Francois Eric , Etienne Marie-Christine , Ferrero Jean-Marc , Peyrade Frederic , Barranger Emmanuel , Bozec Alexandre , Largillier Rémy , Cassuto Ophelie , Viotti Julien , Schiappa Renaud , Milano Gérard
Published: May 2020

Background

Dihydropyrimidine dehydrogenase (DPD) status is an indicator of a marked risk for toxicity following fluoropyrimidine (FP)-based chemotherapy. This notion is well-established for low DPD status but little is known about the clinical impact of high DPD activity. This study examined the possible link between high intrinsic lymphocytic DPD activity and overall survival, progression free survival and response to FP-based treatment in patients treated in our institution.

Methods

Lymphocytic DPD activity was assessed in a group of 136 patients receiving FP-based chemotherapy from 2004 to 2016. There were 105 digestive (77.2%), 24 breast (17.6%) and 7 head and neck cancers (5.2%). Cox or logistic regression models were applied with adjustment on all confounding factors that could modify OS, PFS or response. All models were stratified on the three cancer locations. A cut-off for DPD activity was assessed graphically and analytically.

Results

An optimal cut-off for DPD activity at 0.30 nmol/min/mg protein was identified as the best value for discriminating survivals and response. In multivariate analysis, individual lymphocytic DPD activity was significantly related to overall survival (p = 0.013; HR: 3.35 CI95%[1.27–8.86]), progression-free survival (p < 0.001; HR: 3.15 CI95%[1.75–5.66]) and response rate (p = 0.033; HR: 0.33 CI95%[0.12–0.92]) with a marked detrimental effect associated with high DPD activity.

Conclusions

DPD status screening should result in a two-pronged approach with FP dose reduction in case of low intrinsic DPD and, inversely, an increased FP dose for high intrinsic DPD. In a context of personalized FP-based treatment, this innovative strategy needs to be prospectively validated.
Physical activity and long-term fatigue among colorectal cancer survivors – a population-based prospective study
Authors: Eyl Ruth Elisa , Thong Melissa S. Y. , Carr Prudence R. , Jansen Lina , Koch-Gallenkamp Lena , Hoffmeister Michael , Chang-Claude Jenny , Brenner Hermann , Arndt Volker
Published: May 2020

Background

Evidence suggests that physical activity (PA) is beneficial for reducing fatigue in colorectal cancer (CRC) survivors. However, little is known regarding long-term effects of PA on fatigue and whether pre-diagnosis PA is associated with less fatigue in the years after diagnosis. Our study aimed to investigate the association of pre- and post-diagnosis PA with long-term fatigue in CRC survivors.

Methods

This study used a German population-based cohort of 1781 individuals, diagnosed with CRC in 2003–2014, and alive at five-year follow-up (5YFU). Physical activity was assessed at diagnosis and at 5YFU. Fatigue was assessed by the Fatigue Assessment Questionnaire and the EORTC Quality of Life Questionnaire-Core 30 fatigue subscale at 5YFU. Multivariable linear regression was used to explore associations between pre- and post-diagnosis PA and fatigue at 5YFU.

Results

No evidence was found that pre-diagnosis PA was associated with less fatigue in long-term CRC survivors. Pre-diagnosis work-related PA and vigorous PA were even associated with higher levels of physical (Beta (ß) = 2.52, 95% confidence interval (CI) = 1.14–3.90; ß = 2.03, CI = 0.65–3.41), cognitive (ß = 0.17, CI = 0.05–0.28; ß = 0.13, CI = 0.01–0.25), and affective fatigue (ß = 0.26, CI = 0.07–0.46; ß = 0.21, CI = 0.02–0.40). In cross-sectional analyses, post-diagnosis PA was strongly associated with lower fatigue on all scales.

Conclusions

In this study, pre-diagnosis PA does not appear to be associated with less fatigue among long-term CRC survivors. Our results support the importance of ongoing PA in long-term CRC survivors. Our findings might be used as a basis for further research on specific PA interventions to improve the long-term outcome of CRC survivors.
The impact of having a baby with cleft lip and palate on parents and on parent-baby relationship: the first French prospective multicentre study
Authors:   CLIP team (Cleft Lip & palate Infant Parent), Grollemund Bruno , Dissaux Caroline , Gavelle Pascale , Martínez Carla Pérez , Mullaert Jimmy , Alfaiate Toni , Guedeney Antoine
Published: May 2020

Background

The objective of this prospective, multidisciplinary and multicenter study was to explore the effect of a cleft lip, associated or not with a cleft palate, on parents, on parent-infant relationship, and on the baby’s relational development. It also highlighted how the type of cleft and the timing of the surgery could impact this effect.

Method

158 infants, with Cleft lip with or without Palate, and their parents participated in this multicenter prospective cohort. Clinical evaluations were performed at 4 and 12 months postpartum. The impact on the parents and on the parent-infant relationship was evaluated by the Parenting Stress Index (PSI), the Edinburgh Post-partum Depression Scale (EPDS) and the Impact-on-Family Scale (IOFS). The relational development of the infant was assessed using the Alarm Distress Baby Scale (ADBB). The main criteria used to compare the infants were the severity of cleft and the time of surgery.

Results

The timing of surgery, the type of malformation or the care structure had no effect on social withdrawal behaviors of the child at 4 and 12 months postpartum (ADBB). Furthermore, early intervention significantly decreased maternal stress assessed with the PSI at 4 months. Parents for whom it had been possible to give a prenatal diagnosis were much better prepared to accept the waiting time between birth and the first surgical intervention (IOFS). Higher postpartum depression scores (EPDS) were found for both parents compared to the general population.

Conclusion

A joint assessment of the mental health of both infants and parents is required in the follow-up of cleft lip and palate. Even if most families are remarkably resilient faced with this major cause of stress, a significant proportion of them could require help to deal with the situation, especially during this first year of follow-up. An assessment of the child’s social withdrawal behaviour and of the parental stress and depression appears useful, in order to adapt care to infant and parent’s needs.

Trial registration

ClinicalTrials.gov Identifier:NCT00993993. Registered 10/14/2009 <.
Associations between rapid weight gain in infancy and weight status among urban Aboriginal children participating in the Gudaga study: nine-year results from a cohort study
Authors: Denney-Wilson Elizabeth , Fatema Kaniz , Elcombe Emma , Ingram Suzanne , Harris Mark , Comino Elizabeth
Published: May 2020

Background

Rapid weight gain (RWG) in infants is associated with overweight and obesity in childhood and beyond, highlighting the need for early intervention.

Methods

Data from a birth cohort of Australian Aboriginal and Torres Strait Islander children living in an urban area were analysed to determine the prevalence of RWG in infancy and the association between RWG and overweight and obesity, categorised using both body mass index and waist to height ratio from birth to 9 years.

Results

The prevalence of overweight and obesity is higher in this cohort (at 47%) than the population average. The Australian population as a whole has seen steady increases. In this cohort although the prevalence of combined overweight and obesity remained relatively stable between 2 and 9 years, the proportion of children categorized as obese using BMI has increased. 42% of children who were overweight or obese at 9 years had experienced RWG in infancy. Children were 2.7 and 3.9 times more likely to be overweight at 9 years if they experienced RWG or were overweight at 2 years, respectively.

Conclusion

RWG was common in this cohort and the strongest predictor of excess weight at 2 years and at 9 years. Early intervention is crucial in the first year of life across the whole population to prevent obesity in children. Culturally appropriate interventions developed with the community are required for Aboriginal and Torres Strait Islander babies and their parents.
Concurrent diabetic ketoacidosis and pancreatitis in Paediatric acute lymphoblastic leukemia receiving L-asparaginase
Authors: Jameel Patel Zeeshan , Lohiya Sham , Dongre Amol , Damke Sachin , Lakhkar Bhavana B.
Published: May 2020

Background

Although hyperglycemia and pancreatitis are known side effects of L-asparaginase, both contributing to the development of diabetic ketoacidosis (DKA) is unfamiliar in literature.

Case presentation

We report a case of an adolescent girl, recently diagnosed with ALL, who presented with pain in abdomen and breathing difficulty following chemotherapy with L-asparaginase. On subsequent evaluation, she was found to have high anion gap metabolic acidosis, hyperglycemia and ketonuria. Ultrasonogram showed bulky pancreas. DKA was managed with fluid correction and insulin infusion. Pancreatitis was managed conservatively. She recovered completely with resolution of symptoms and without any major adverse events despite having such severe complications.

Conclusion

We conclude that the combination of DKA and pancreatitis is a rare occurrence with significant morbidity and mortality. We recommend a close monitoring of blood glucose levels for hyperglycemia as well as a high index of clinical suspicion for pancreatitis in patients with ALL receiving L-asparaginase.
Weight misperception and psychological symptoms from adolescence to young adulthood: longitudinal study of an ethnically diverse UK cohort
Authors: Elia Christelle , Karamanos Alexis , Silva Maria João , O’Connor Maeve , Lu Yao , Dregan Alexandru , Huang Peiyuan , O’Keeffe Majella , Cruickshank J. Kennedy , Enayat Elli Z. , Cassidy Aidan , Molaodi Oarabile R. , Maynard Maria , Harding Seeromanie
Published: May 2020

Background

To evaluate the association between weight misperception and psychological symptoms in the Determinants of young Adults Social well-being and Health (DASH) longitudinal study.

Methods

A longitudinal sample of 3227 adolescents, in 49 secondary schools in London, aged 11–16 years participated in 2002/2003 and were followed up in 2005/2006. A sub-sample (N = 595) was followed up again at ages 21–23 years in 2012/2013. An index of weight misperception was derived from weight perception and measured weight. Psychological well- being was measured using the Strengths and Difficulties Questionnaire at 11–16 years and the General Health Questionnaire at 21–23 years. Associations with weight misperception was assessed using regression models, adjusted for socio-economic and lifestyle factors.

Results

White British males and females were more likely than ethnic minority peers to report accurate perceptions of measured weight. At 11-13y, 46% females and 38% males did not have an accurate perception of their measured weight. The comparable figures at 14-16y were 42 and 40%. Compared with male adolescents, more females perceived themselves as overweight or were unsure of their weight but measured normal weight, and this was more pronounced among Indians, Pakistanis and Bangladeshis. At 14-16y, more males perceived themselves as underweight but measured normal weight, and this was more pronounced among Indians. Compared with those who had an accurate perception of their normal weight, a higher likelihood of probable clinically-relevant psychological symptoms was observed among those who measured normal weight but perceived themselves to be underweight (females Odds Ratio (OR) = 1.87 95% CI 1.03–3.40; males OR = 2.34 95% CI 1.47–3.71), overweight (females only OR = 2.06 95% CI 1.10–3.87), or unsure of their weight (males only OR = 1.61 95% CI 1.04–2.49). Among females, the association was driven by internalising rather than externalising symptoms. An accurate perception of overweight was associated with higher psychological symptoms in adolescence and early 20s. Ethnic specific effects were not evident.

Conclusion

Weight misperception may be an important determinant of psychological symptoms in young people, with an accurate perception of normal weight status being protective. Culturally targeted interventions should be considered to promote healthy perceptions of body image.
Feasibility of coding-based Charlson comorbidity index for hospitalized patients in China, a representative developing country
Authors:   on behalf of China collaborative study on acute kidney injury, Mo Liyi , Xie Zhen , Liu Guohui , He Qiang , Mo Zhiming , Wu Yanhua , Wang Wenji , Ding Feng , Liao Yuanjiang , Hao Li , Lu Chen , Sun Jin , Xu Libin , Zhang Yusheng , Ghappar Rizwangul , Peng Hongwei , Wei Xiaohong , Xie Jinglie , Chen Yuanhan , Liang Xinling
Published: May 2020

Background

The Charlson Comorbidity Index (CCI) can be automatically calculated from the International Classification of Disease (ICD) code. However, the feasibility of this transformation has not been acknowledged, particularly in hospitals without a qualified ICD coding system. Here, we investigated the utility of coding-based CCI in China.

Methods

A multi-center, population-based, retrospective observational study was conducted, using a dataset incorporating 2,464,395 adult subjects from 15 hospitals. CCI was calculated using both ICD-10-based and diagnosis-based method, according to the transformation rule reported previously and to the literal description from discharge diagnosis, respectively. A κ coefficient of variation was used as a measure of agreement between the above two methods for each hospital. The discriminative abilities of the two methods were compared using the receiver-of-operating characteristic curve (ROC) for prediction of in-hospital mortality.

Results

Total agreement between the ICD-based and diagnosis-based CCI for each index ranged from 86.1 to 100%, with κ coefficients from 0.210 [95% confidence interval (CI) 0.208–0.212] to 0.932 (95% CI 0.924–0.940). None of the 19 indices of CCI had a κ coefficient > 0.75 in all the hospitals included for study. The area under the curve of ROC for in-hospital mortality of all 15 hospitals was significantly lower for ICD-based than diagnosis-based CCI [0.735 (0.732, 0.739) vs 0.760 (0.757, 0.764)], indicative of more limited discriminative ability of the ICD-based calculation.

Conclusions

CCI calculated using ICD-10 coding did not agree with diagnosis-based CCI. ICD-based CCI displayed diminished discrimination performance in terms of in-hospital mortality, indicating that this method is not promising for CCI scoring in China under the present circumstances.
Primary tumor location affects recurrence-free survival for patients with colorectal liver metastases after hepatectomy: a propensity score matching analysis
Authors: Zhang Yuanping , Wang Yongjin , Yuan Yichuan , Qiu Jiliang , Qiu Yuxiong , He Wei , Zheng Yun , Wang Zhiqiang , Gu Yangkui , Lu Zhenhai , Chen Gong , Ding Peirong , Wu Xiaojun , Pan Zhizhong , Wan Desen , Li Yuhong , Xu Ruihua , Yuan Yunfei , Li Binkui
Published: May 2020

Background

Whether primary tumor location of colorectal cancer (CRC) affects survival of patients after resection of liver metastases remains controversial. This study was conducted to investigate the differences in clinicopathological characteristics and prognosis between right-sided CRC and left-sided CRC patients with liver metastases after hepatectomy.

Methods

From 2002 to 2018, 611 patients with colorectal liver metastases (CRLM) who underwent hepatectomy at our center were reviewed. Primary tumors located from the cecum to transverse colon were defined as right-sided group (n = 141); tumors located from the splenic flexure to rectum were defined as left-sided group (n = 470). Patients were compared between two groups before and after a 1:1 propensity score matching (PSM) analysis.

Results

Before PSM, median survival time and 5-year overall survival (OS) rate in right-sided group were 77 months and 56.3%, and those in left-sided group were 64 months and 51.1%, respectively. After PSM, median survival time and 5-year OS rate in right-sided group were 77 months and 55.9%, and those in left-sided group were 58.8 months and 47.3%, respectively. The OS rates did not differ between two groups before and after PSM (P = 0.575, P = 0.453). However, significant different recurrence-free survival (RFS) rate was found before and after PSM between right-sided and left-sided group (P = 0.028, P = 0.003).

Conclusions

Compared to patients with left-sided primary tumors, patients with right-sided primary tumors had a worse RFS but similar OS. Careful preoperative evaluation, intensive preoperative chemotherapy, and frequent follow-up to detect early recurrence might be justified for CRLM patients with right-sided primary tumors.
Protection from DNA re-methylation by transcription factors in primordial germ cells and pre-implantation embryos can explain trans-generational epigenetic inheritance
Authors: Kremsky Isaac , Corces Victor G.
Published: May 2020

Background

A growing body of evidence suggests that certain epiphenotypes can be passed across generations via both the male and female germlines of mammals. These observations have been difficult to explain owing to a global loss of the majority of known epigenetic marks present in parental chromosomes during primordial germ cell development and after fertilization.

Results

By integrating previously published BS-seq, DNase-seq, ATAC-seq, and RNA-seq data collected during multiple stages of primordial germ cell and pre-implantation development, we find that the methylation status of the majority of CpGs genome-wide is restored after global de-methylation, despite the fact that global CpG methylation drops to 10% in primordial germ cells and 20% in the inner cell mass of the blastocyst. We estimate the proportion of such CpGs with preserved methylation status to be 78%. Further, we find that CpGs at sites bound by transcription factors during the global re-methylation phases of germline and embryonic development remain hypomethylated across all developmental stages observed. On the other hand, CpGs at sites not bound by transcription factors during the global re-methylation phase have high methylation levels prior to global de-methylation, become de-methylated during global de-methylation, and then become re-methylated.

Conclusions

The results suggest that transcription factors can act as carriers of epigenetic information during germ cell and pre-implantation development by ensuring that the methylation status of CpGs is maintained. These findings provide the basis for a mechanistic description of trans-generational inheritance of epigenetic information in mammals.
Effect of an interprofessional care concept on the hospitalization of nursing home residents: study protocol for a cluster-randomized controlled trial
Authors: Piotrowski Alexandra , Meyer Martha , Burkholder Iris , Renaud Dagmar , Müller Markus Alexander , Lehr Thorsten , Laag Sonja , Meiser Joachim , Manderscheid Lisa , Köberlein-Neu Juliane
Published: May 2020

Background

The rising number of nursing home (NH) residents and their increasingly complex treatment needs pose a challenge to the German health care system. In Germany, there is no specialized geriatric medical care for NH residents. Nursing staff and general practitioners (GPs) in particular have to compensate for the additional demand, which is compounded by organizational and structural hurdles. As a result, avoidable emergency calls and hospital admissions occur.

In the SaarPHIR project (Saarländische PflegeHeimversorgung Integriert Regelhaft), a complex intervention focusing on a medical care concept was developed in a participatory practice-based approach involving NH representatives and GPs. The complex intervention addresses the collaboration between nurses and GPs and aims to help restructure and optimize the existing daily care routine. It is expected to improve the medical care of geriatric patients in NHs and reduce stressful, costly hospital admissions. The intervention was pilot-tested during the first 12 months of the project. In the present study, its effectiveness, cost-effectiveness, and safety will be evaluated.

Methods

The study is a cluster-randomized controlled trial, comparing an intervention group with a control group. The intervention includes a concept of interprofessional collaboration, in which GPs group into regional cooperating teams. Teams are encouraged to cooperate more closely with NH staff and to provide on-call schedules, pre-weekend visits, joint team meetings, joint documentation, and improved medication safety. At least 32 NHs in Saarland, Germany (with at least 50 residents each) will be included and monitored for 12 months. The primary endpoint is hospitalization. Secondary endpoints are quality of life, quality of care, and medication safety. The control group receives treatment as usual. Process evaluation and health economic evaluation accompany the study. The data set contains claims data from German statutory health insurance companies as well as primary data. Analysis will be conducted using a generalized linear mixed model.

Conclusion

A reduction in hospital admissions of NH residents and relevant changes in secondary endpoints are expected. In turn, these will have a positive impact on the economic assessment.

Trial registration

German Clinical Trials Register: DRKS00017129. Registered on 23 April 2019. https://www.drks.de/drks_web/setLocale_EN.do.
Metabolic engineering of a fast-growing cyanobacterium Synechococcus elongatus PCC 11801 for photoautotrophic production of succinic acid
Authors: Sengupta Shinjinee , Jaiswal Damini , Sengupta Annesha , Shah Shikha , Gadagkar Shruti , Wangikar Pramod P.
Published: May 2020

Background

Cyanobacteria, a group of photosynthetic prokaryotes, are being increasingly explored for direct conversion of carbon dioxide to useful chemicals. However, efforts to engineer these photoautotrophs have resulted in low product titers. This may be ascribed to the bottlenecks in metabolic pathways, which need to be identified for rational engineering. We engineered the recently reported, fast-growing and robust cyanobacterium,Synechococcus elongatusPCC 11801 to produce succinate, an important platform chemical. Previously, engineering of the model cyanobacteriumS. elongatusPCC 7942 has resulted in succinate titer of 0.43 g l−1in 8 days.

Results

Building on the previous report, expression of α-ketoglutarate decarboxylase, succinate semialdehyde dehydrogenase and phosphoenolpyruvate carboxylase yielded a succinate titer of 0.6 g l−1in 5 days suggesting that PCC 11801 is better suited as host for production. Profiling of the engineered strains for 57 intermediate metabolites, a number of enzymes and qualitative analysis of key transcripts revealed potential flux control points. Based on this, we evaluated the effects of overexpression of sedoheptulose-1,7-bisphosphatase, citrate synthase and succinate transporters and knockout of succinate dehydrogenase and glycogen synthase A. The final construct with seven genes overexpressed and two genes knocked out resulted in photoautotrophic production of 0.93 g l−1succinate in 5 days.

Conclusion

While the fast-growing strain PCC 11801 yielded a much higher titer than the model strain, the efficient photoautotrophy of this novel isolate needs to be harnessed further for the production of desired chemicals. Engineered strains ofS. elongatusPCC 11801 showed dramatic alterations in the levels of several metabolites suggesting far reaching effects of pathway engineering. Attempts to overexpress enzymes deemed to be flux controlling led to the emergence of other potential rate-limiting steps. Thus, this process of debottlenecking of the pathway needs to be repeated several times to obtain a significantly superior succinate titer.
Deciphering the transcriptional regulatory networks that control size, color, and oil content in Brassica rapa seeds
Authors: Niu Yue , Wu Limin , Li Yanhua , Huang Hualei , Qian Mingchao , Sun Wei , Zhu Hong , Xu Yuanfang , Fan Yonghai , Mahmood Umer , Xu Benbo , Zhang Kai , Qu Cunmin , Li Jiana , Lu Kun
Published: May 2020

Background

Brassica rapais an important oilseed and vegetable crop species and is the A subgenome donor of two important oilseedBrassicacrops,Brassica napusandBrassica juncea. Although seed size (SZ), seed color (SC), and oil content (OC) substantially affect seed yield and quality, the mechanisms regulating these traits inBrassicacrops remain unclear.

Results

We collected seeds from a pair ofB. rapaaccessions with significantly different SZ, SC, and OC at seven seed developmental stages (every 7 days from 7 to 49 days after pollination), and identified 28,954 differentially expressed genes (DEGs) from seven pairwise comparisons between accessions at each developmental stage.K-means clustering identified a group of cell cycle-related genes closely connected to variation in SZ ofB. rapa. A weighted correlation analysis using the WGCNA package in R revealed two important co-expression modules comprising genes whose expression was positively correlated with SZ increase and negatively correlated with seed yellowness, respectively. Upregulated expression of cell cycle-related genes in one module was important for the G2/M cell cycle transition, and the transcription factorBra.A05TSO1seemed to positively stimulate the expression of twoCYCB1;2genes to promote seed development. In the second module, a conserved complex regulated by the transcription factor TT8 appear to determine SC through downregulation ofTT8and its target genesTT3,TT18, andANR. In the third module, WRI1 and FUS3 were conserved to increase the seed OC, andBra.A03GRF5was revealed as a key transcription factor on lipid biosynthesis. Further, upregulation of genes involved in triacylglycerol biosynthesis and storage in the seed oil body may increase OC. We further validated the accuracy of the transcriptome data by quantitative real-time PCR of 15 DEGs. Finally, we used our results to construct detailed models to clarify the regulatory mechanisms underlying variations in SZ, SC, and OC inB. rapa.

Conclusions

This study provides insight into the regulatory mechanisms underlying the variations of SZ, SC, and OC in plants based on transcriptome comparison. The findings hold great promise for improving seed yield, quality and OC through genetic engineering of critical genes in future molecular breeding.
Polygenic risk scores: from research tools to clinical instruments
Authors: Lewis Cathryn M. , Vassos Evangelos
Published: May 2020

Genome-wide association studies have shown unequivocally that common complex disorders have a polygenic genetic architecture and have enabled researchers to identify genetic variants associated with diseases. These variants can be combined into a polygenic risk score that captures part of an individual’s susceptibility to diseases. Polygenic risk scores have been widely applied in research studies, confirming the association between the scores and disease status, but their clinical utility has yet to be established. Polygenic risk scores may be used to estimate an individual’s lifetime genetic risk of disease, but the current discriminative ability is low in the general population. Clinical implementation of polygenic risk score (PRS) may be useful in cohorts where there is a higher prior probability of disease, for example, in early stages of diseases to assist in diagnosis or to inform treatment choices. Important considerations are the weaker evidence base in application to non-European ancestry and the challenges in translating an individual’s PRS from a percentile of a normal distribution to a lifetime disease risk. In this review, we consider how PRS may be informative at different points in the disease trajectory giving examples of progress in the field and discussing obstacles that need to be addressed before clinical implementation.
Sex hormone-binding globulin and arthritis: a Mendelian randomization study
Authors: Qu Zihao , Huang Jiawei , Yang Fangkun , Hong Jianqiao , Wang Wei , Yan Shigui
Published: May 2020

Background

Sex hormone-binding globulin (SHBG) has been reported to be a risk factor associated with the development of arthritis by previous observational studies more so of three common forms of arthritis: osteoarthritis (OA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). This study aimed to determine whether the concentrations of circulating SHBG are causally associated with the risk of OA, RA, and AS.

Methods

The two-sample Mendelian randomization (MR) approach was used for this study. The inverse-variance-weighted (IVW) method was used for the main analysis. Single-nucleotide polymorphisms (SNPs) associated with SHBG were selected from a large genome-wide association study (GWAS) of 28,837 European individuals. The summary statistics for OA, RA, and AS were extracted from the UK Biobank Resource (n = 361,141) and a GWAS dataset (n = 455,221).

Results

Positive causal associations were found between circulating SHBG concentrations and OA (effect = 1.086; 95% CI, 1.009 to 1.168;P = 0.027) and RA (effect = 1.003; 95% CI, 1.000 to 1.007;P = 0.047) in overall analyses. However, there was no evidence of association between SHBG levels and AS. Based on the stratification of skeletal sites, SHBG levels were found to be significantly associated with hip OA (effect = 1.423; 95% CI, 1.219 to 1.660;P = 7.753 × 10−6). However, this was not the case with knee OA.

Conclusions

There were positive causal effects of circulating SHBG on the development of OA and RA. Moreover, there was a site-specific association between SHBG and hip OA. Evidently, measurement of SHBG in serum could be valuable in the clinical assessment of arthritis especially in early screening and prevention of OA and RA. However, the mechanisms by which SHBG plays causal roles in the development of arthritis require further investigations.
An economic analysis of transhumance in the Central Spanish Pyrenees
Authors: Fernández-Giménez María E. , Ritten John
Published: May 2020

The ecological and risk -management rationales for livestock mobility are well established. Yet, few studies evaluate the economic benefits and costs of maintaining or resuming mobile, extensive livestock production compared to sedentary or semi-extensive production. Here, we empirically evaluate pastoralists’ claims that transhumance, a specific type of long-distance herd mobility, is a more profitable system compared to semi-extensive production in the Central Spanish Pyrenees. Specifically, we use enterprise budget data from transhumant and semi-extensive operations to develop a baseline typical sheep operation budget. We then use partial budget analysis coupled with economic simulations to determine the conditions under which transhumance by truck or on foot becomes profitable relative to semi-extensive production. We find that transhumance by foot is more profitable than transhumance by truck and that relative profitability compared to semi-extensive production depends on operational scale, feed prices, and the lambing rates (productivity) of each system. Over all simulated scenarios, transhumance is more profitable 64–78% of the time. This analysis thus provides initial evidence of the economic rationality of transhumance under contemporary environmental and economic conditions, filling a notable gap in research on the economics of transhumance. Future research could expand the analysis to cattle operations and to other regions of Spain, assess the full social and environmental benefits and costs of transhumance, and evaluate the effects of exogenous factors like drought on production costs and profitability to determine if transhumance is an adaptive strategy under a changing climate. The analysis we present could be used as a basis to develop and pilot test interactive budgeting tools that support herder decision-making and planning under economic and environmental uncertainty.
Amid COVID-19: the importance of developing an positive adverse drug reaction (ADR) and medical device incident (MDI) reporting culture for Global Health and public safety
Authors: Elbeddini Ali , Yeats Aniko , Lee Stephanie
Published: May 2020

Amid COVID-19 Crisis, reporting adverse drug reactions (ADRs) and medical device incidents (MDIs) to Health Canada or health authorities in every country is crucial for monitoring medication safety and improving public health. Health Canada, for example, through their online database, has facilitated the process of reporting side effects relating to drugs and medical devices. However, several patients and health care professionals still fail to voluntarily report adverse events. For health care providers, some barriers to reporting may include fear of negative feedback, apathy, legal concerns, and uncertainty about whether an incident qualifies as an ADR.

In the current COVID-19 Crisis, it is especially important for health care providers to be diligent about reporting Adverse Drug Reactions (ADRs), since misinformation propagated by the media is causing patients to misuse certain medications. We need to shift the current thought process about ADR reporting in order to encourage a positive reporting culture by patients and health care providers.
Role of ncRNAs in modulation of liver fibrosis by extracellular vesicles
Authors: Chiabotto Giulia , Camussi Giovanni , Bruno Stefania
Published: May 2020

Extracellular vesicles (EVs) are small membrane vesicles carrying bioactive lipids, proteins and nucleic acids of the cell of origin. In particular, EVs carry non-coding RNAs (ncRNAs) and the vesicle membrane may protect them from degradation. Once released within the extracellular space, EVs can transfer their cargo, including ncRNAs, to neighboring or distant cells, thus inducing phenotypical and functional changes that may be relevant in several physio-pathological conditions. This review provides an overview of the role of EV-carried ncRNAs in the modulation of liver fibrosis. In particular, we focused on EV-associated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) involved into the development of liver fibrosis and on the potential use of EV-associated ncRNAs as diagnostic and prognostic biomarkers of liver fibrosis.
Potential agricultural and environmental benefits of mulches—a review
Authors: Iqbal Rashid , Raza Muhammad Aown Sammar , Valipour Mohammad , Saleem Muhammad Farrukh , Zaheer Muhammad Saqlain , Ahmad Salman , Toleikiene Monika , Haider Imran , Aslam Muhammad Usman , Nazar Muhammad Adnan
Published: May 2020

Rapid industrialization and urbanization have resulted in elevated global temperature over the years consequently disturbing the balance of agro-ecological systems worldwide. Therefore, new eco-friendly agricultural practices for sustainable food production are needed. Mulching could potentially serve the purpose by reducing soil evaporation, conserving moisture, controlling soil temperature, reducing weed growth, and improving microbial activities. Additionally, mulches could provide economical, aesthetic, and environmental advantages to agriculture and landscape. Moreover, in the restoration sites, mulches are widely used for the plantation of trees which need no significant care. Mulches combat with different stress conditions in agricultural lands as well as in landscapes. This review paper focuses on multiple significant impacts of mulches for the production and establishment of different crops in nature. Mulches conserve the soil moisture, enhance the nutrients status of soil, control the erosion losses, suppress the weeds in crop plants, and remove the residual effects of pesticides, fertilizers, and heavy metals. Mulches improve the aesthetic value of landscapes and economic value of crops. This paper also describes some problems associated with various mulch materials. There are contradictions about mulching materials as some researchers favor mulches and others have denoted some concerns. The selection of mulching material is important with respect to crop type, management practices, and climatic conditions. The appropriate mulching technique could provide the aforementioned benefits to the agro-ecological systems. Therefore, the impacts of low-cost, eco-friendly, and biodegradable mulching materials on soil microbes, nutrient balance, plant growth, and soil erosion should be explored in the future.
Assessment of vascular stiffness using different modalities in patients with systemic lupus erythematosus: a case control study
Authors: Ammar Waleed , Taha Moataz , Baligh Essam , Osama Dina
Published: May 2020

Background

Cardiovascular disease is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. Accurate risk stratification would require a simple, non-invasive index integrating all traditional and emerging risk factors. Vascular stiffness fulfills these requirements and has better predictive value for cardiovascular events than traditional risk factors in hypertensives and patients with coronary artery disease. Our aim was to determine whether arterial stiffness is increased in SLE patients compared to healthy controls and to correlate the arterial stiffness in SLE patients with cardiovascular risk factors, namely, hypertension and diabetes mellitus.

Results

This study included 50 SLE patients and 50 age- and gender-matched healthy individuals. SLE patients had higher median aortic stiffness index (SI) and lower strain and distensibility, compared to controls (p value for all < 0.001). SLE patients had significantly impaired flow-mediated dilation (FMD) compared to controls: the median (range) in SLE patients was 8.82 (2.5–21.87), compared to 19 (12–37.5) in controls (z = − 7.695, p ˂ 0.001). Regarding quality arterial stiffness (QAS) parameters, SLE patients had significantly lower median carotid distension, distensibility coefficient, and compliance coefficient, with higher median carotid SI, carotid pulse wave velocity (PWV), and augmentation index (AI), compared to controls (p value for all ≤ 0.001). SLE patients had a higher median cf-PWV 6.5 m/s (4.8–11.8), compared to a median of 4.6 m/s (3.8–6.9) in controls (z = − 8.193, p ˂ 0.001). Linear regression analysis to adjust for hypertension and diabetes mellitus yielded a statistically significant difference between both groups for all of the above parameters (p = 0.014 for maximum carotid intima media thickness (IMT) and < 0.001 for remaining parameters), with the exception of the maximum carotid augmentation index (p = 0.184).

Conclusion

SLE patients have significantly increased arterial stiffness and impaired FMD compared to healthy controls. This is true even after adjusting for hypertension and diabetes mellitus, highlighting the fact that SLE could be an independent cardiovascular risk factor. These findings emphasize the need for early management of SLE together with aggressive risk factor modification.
Development of the RMT20, a composite screener to identify common mental disorders
Authors: Batterham Philip J. , Sunderland Matthew , Carragher Natacha , Calear Alison L.
Published: May 2020

Background

There are few very brief measures that accurately identify multiple common mental disorders.

Aims

The aim of this study was to develop and assess the psychometric properties of a new composite measure to screen for five common mental disorders.

Method

Two cross-sectional psychometric surveys were used to develop (n = 3175) and validate (n = 3620) the new measure, the Rapid Measurement Toolkit-20 (RMT20) against diagnostic criteria. The RMT20 was tested against a DSM-5 clinical checklist for major depression, generalised anxiety disorder, panic disorder, social anxiety disorder and post-traumatic stress disorder, with comparison with two measures of general psychological distress: the Kessler-10 and Distress Questionnaire-5.

Results

The area under the curve for the RMT20 was significantly greater than for the distress measures, ranging from 0.86 to 0.92 across the five disorders. Sensitivity and specificity at prescribed cut-points were excellent, with sensitivity ranging from 0.85 to 0.93 and specificity ranging from 0.73 to 0.83 across the five disorders.

Conclusions

The RMT20 outperformed two established scales assessing general psychological distress, is free to use and has low respondent burden. The measure is well-suited to clinical screening, internet-based screening and large-scale epidemiological surveys.