bluuebunny/crossref_metadata_2025 huggingface dataset:
The burden of depressive disorders in musculoskeletal diseases: is there an association between mood and inflammation?
Authors: Chimenti Maria Sole , Fonti Giulia Lavinia , Conigliaro Paola , Triggianese Paola , Bianciardi Emanuela , Coviello Marialuce , Lombardozzi Ginevra , Tarantino Giulia , Niolu Cinzia , Siracusano Alberto , Perricone Roberto
Published: January 2021

Importance

Evidence emerged concerning how inflammatory arthritis and mood disorders can often occur in the same patient and show a similar clinical pattern. An overview of the rheumatological and psychiatric aspects of these diseases can certainly be useful for the improvement of patients' clinical and therapeutic management.

Objective

The aim of this narrative review was to summarize existing literature about common pathogenetic and clinical aspects as a means of improving management and therapeutic approach in patients affected by rheumatoid arthritis, psoriatic arthritis and spondyloarthritis. Outcomes such as disease activity indexes and patient reported outcomes (PROs) were considered.

Findings

Common pathogenetic pathways emerged between inflammatory arthritis and mood disorders. Pro-inflammatory mechanisms, such as TNFα, IL-6, IL-17 and oxidative stress factors as well as neurotransmitter alterations at the level of CNS and blood–brain barrier (BBB) cells are involved. The activation of these common pathogenetic pathways is, also, affected by the same triggers, such as smoking, stress, lifestyle, and evidence has emerged concerning the possibility of the clinical efficacy of using the same therapeutic approaches.

Conclusions

The main causes of the variability in clinical studies outcomes are the rheumatological diseases considered, the prevalence of depression in the general population and in patients with rheumatological diseases and the type of depressive symptom examined. Patients affected by inflammatory arthritis can present symptoms and signs in common with mood disorders, leading to possible clinical overlap. There are still few studies analyzing this concept: they are extremely heterogeneous, both in the characteristics of the population taken into consideration and in the methods used for the definition of depressive disorder, but the suggestions of the data obtained so far are promising and deserve to be pursued.
Correction to: Tracking Japan’s development assistance for health, 2012–2016
Authors: Nomura Shuhei , Sakamoto Haruka , Sugai Maaya Kita , Nakamura Haruyo , Maruyama-Sakurai Keiko , Lee Sangnim , Ishizuka Aya , Shibuya Kenji
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
Participatory analysis of groundnut (Arachis hypogaea L.) cropping system and production constraints in Burkina Faso
Authors: Sinare Boubacar , Miningou Amos , Nebié Baloua , Eleblu John , Kwadwo Ofori , Traoré Appolinaire , Zagre Bertin , Desmae Haile
Published: January 2021

Background

Groundnut is one of the major legume crops grown as food and cash crop across the different agroecological zones of Burkina Faso. It is ranked the 2nd important legume crop for household food, nutrition, and income generation for both rural and urban zones, contributing significantly to food supply and economy of the country. Despite its importance and breeding efforts to develop improved varieties, groundnut productivity remains low. Assessing and describing the present groundnut cropping system and production constraints as well as gender dynamics in the main production areas will help in defining the groundnut breeding priorities.

Methods

A participatory rural appraisal study was conducted in three groundnut production regions (central-eastern, central-northern, and central-western). In each region, 4 villages were selected with a total of 124 farmers interviewed to collect data on socio-demographics, farming systems, cropping practices, and production constraints. Data analysis was carried out for qualitative and quantitative variables using STATA 14. Analysis of variance was conducted across regions and gender, and also between and within regions. Kendall’s coefficients were determined for qualitative variables across regions for the constraints using the pairwise rank. Pearson’s correlation was carried out to assess the relationship between variables, and the chi-square test was used to assess the difference in farmer preferences.

Results

The study revealed a cropping system of groundnut in an environment largely affected by climate change and in a subsistence and extensive agriculture. There is a variation in the groundnut cropping system across the regions. Gender plays a key role in the production of the groundnut, and 48.39% of women are engaged in groundnut cropping with less access to land and production resources. A yield gap between men and women was observed with men achieving more yield than women. There was a strong correlation between the use of improved varieties and technical assistance. A strong correlation was observed between farm size and production, and farm size and sex denoting an extensive production. Production constraints, although similar, were perceived and ranked differently between regions. The lack of improved varieties, absence of agricultural credit, lack of production tools, the high price of seeds, the high price of fertilizer, drought, and disease are some of the important constraints affecting groundnut productivity.

Conclusion

This study provides a recent view of groundnut cropping, allowing a good understanding of the farmers’ situation. The result will contribute to the refining of breeding priorities and guide further activities in groundnut breeding in Burkina Faso.
Various forms of alcohol use and their predictors among pregnant women in post conflict northern Uganda: a cross sectional study
Authors: Agiresaasi Apophia , Nassanga Goretti , Maina Gakenia Wamuyu , Kiguli Juliet , Nabiwemba Elizabeth , Tumwesigye Nazarius Mbona
Published: January 2021

Background

Alcohol use during pregnancy has been associated with several births and developmental disorders. This study set out to determine the various forms of alcohol consumption among pregnant women and their predictors in post conflict Northern Uganda.

Methods

In the months of May to June 2019, we conducted a cross sectional study among 420 pregnant women seeking antenatal care services at both Government and private health facilities in Gulu, Kitgum and Pader districts in Northern Uganda. We asked them about consumption of various alcoholic beverages. A three stage stratified cluster sampling approach was used and study participants randomly selected from health facilities of interest. We used descriptive statistics to estimate the prevalence of various forms of alcohol use. The chi- square test and logistic regression were used to assess associations of alcohol use among respondents and their socio - demographic and other characteristics.

Results

Overall 99 women (23.6%) reported current alcohol use (any amount). Up to 11% (N = 11) of all drinkers were identified by the AUDIT to be women with problem drinking behavior, 8% (N = 8) of women reported hazardous drinking and only four (4%) were women with active alcohol dependent behavior. Predictors of maternal alcohol use included pre-pregnancy alcohol consumption, knowledge, attitude, education level, parity and residence.

Conclusions

This study indicates that alcohol use (any mount) during pregnancy is high while alcohol dependence, problematic and hazardous drinking is low. Knowledge and attitude were important predictors of alcohol use. While alleviating alcohol use, development partners and relevant government departments should consider communication and other interventions that increase knowledge and risk perception on maternal drinking. Other risk factors that predict maternal drinking such as prior alcohol use, residence and parity should be mitigated or eliminated.
How the pan-genome is changing crop genomics and improvement
Authors: Della Coletta Rafael , Qiu Yinjie , Ou Shujun , Hufford Matthew B. , Hirsch Candice N.
Published: January 2021

Crop genomics has seen dramatic advances in recent years due to improvements in sequencing technology, assembly methods, and computational resources. These advances have led to the development of new tools to facilitate crop improvement. The study of structural variation within species and the characterization of the pan-genome has revealed extensive genome content variation among individuals within a species that is paradigm shifting to crop genomics and improvement. Here, we review advances in crop genomics and how utilization of these tools is shifting in light of pan-genomes that are becoming available for many crop species.
SpRY greatly expands the genome editing scope in rice with highly flexible PAM recognition
Authors: Xu Ziyan , Kuang Yongjie , Ren Bin , Yan Daqi , Yan Fang , Spetz Carl , Sun Wenxian , Wang Guirong , Zhou Xueping , Zhou Huanbin
Published: January 2021

Background

Plant genome engineering mediated by various CRISPR-based tools requires specific protospacer adjacent motifs (PAMs), such as the well-performed NGG, NG, and NNG, to initiate target recognition, which notably restricts the editable range of the plant genome.

Results

In this study, we thoroughly investigate the nuclease activity and the PAM preference of two structurally engineered SpCas9 variants, SpG and SpRY, in transgenic rice. Our study shows that SpG nuclease favors NGD PAMs, albeit less efficiently than the previously described SpCas9-NG, and that SpRY nuclease achieves efficient editing across a wide range of genomic loci, exhibiting a preference of NGD as well as NAN PAMs. Furthermore, SpRY-fused cytidine deaminase hAID*Δ and adenosine deaminase TadA8e are generated, respectively. These constructs efficiently induce C-to-T and A-to-G conversions in the target genes toward various non-canonical PAMs, including non-G PAMs. Remarkably, high-frequency self-editing events (indels and DNA fragments deletion) in the integrated T-DNA fragments as a result of the nuclease activity of SpRY are observed, whereas the self-editing of SpRY nickase-mediated base editor is quite low in transgenic rice lines.

Conclusions

The broad PAM compatibility of SpRY greatly expands the targeting scope of CRISPR-based tools in plant genome engineering.
Unraveling city-specific signature and identifying sample origin locations for the data from CAMDA MetaSUB challenge
Authors: Zhang Runzhi , Walker Alejandro R. , Datta Susmita
Published: January 2021

Background

Composition of microbial communities can be location-specific, and the different abundance of taxon within location could help us to unravel city-specific signature and predict the sample origin locations accurately. In this study, the whole genome shotgun (WGS) metagenomics data from samples across 16 cities around the world and samples from another 8 cities were provided as the main and mystery datasets respectively as the part of the CAMDA 2019 MetaSUB “Forensic Challenge”. The feature selecting, normalization, three methods of machine learning, PCoA (Principal Coordinates Analysis) and ANCOM (Analysis of composition of microbiomes) were conducted for both the main and mystery datasets.

Results

Features selecting, combined with the machines learning methods, revealed that the combination of the common features was effective for predicting the origin of the samples. The average error rates of 11.93 and 30.37% of three machine learning methods were obtained for main and mystery datasets respectively. Using the samples from main dataset to predict the labels of samples from mystery dataset, nearly 89.98% of the test samples could be correctly labeled as “mystery” samples. PCoA showed that nearly 60% of the total variability of the data could be explained by the first two PCoA axes. Although many cities overlapped, the separation of some cities was found in PCoA. The results of ANCOM, combined with importance score from the Random Forest, indicated that the common “family”, “order” of the main-dataset and the common “order” of the mystery dataset provided the most efficient information for prediction respectively.

Conclusions

The results of the classification suggested that the composition of the microbiomes was distinctive across the cities, which could be used to identify the sample origins. This was also supported by the results from ANCOM and importance score from the RF. In addition, the accuracy of the prediction could be improved by more samples and better sequencing depth.
Significance of serum branched-chain amino acid to tyrosine ratio measurement in athletes with high skeletal muscle mass
Authors: Tsunekawa Katsuhiko , Matsumoto Ryutaro , Ushiki Kazumi , Martha Larasati , Shoho Yoshifumi , Yanagawa Yoshimaro , Ishigaki Hirotaka , Yoshida Akihiro , Araki Osamu , Nakajima Kiyomi , Kimura Takao , Murakami Masami
Published: January 2021

Background

Few nutritional markers reflect the hypermetabolic state of athletes with high levels of skeletal muscle. Although branched-chain amino acids (BCAA) play crucial roles in protein metabolism in skeletal muscle, the relationship between skeletal muscle mass and amino acid imbalances caused by the metabolism of BCAA and aromatic amino acids remains unclear. The aim of this study is to test the hypothesis that athletes with high levels of skeletal muscle mass have plasma amino acid imbalances, assessed by serum BCAA to tyrosine ratio (BTR) which can be measured conveniently.

Methods

The study enrolled 111 young Japanese men: 70 wrestling athletes and 41 controls. None of them were under any medications, extreme dietary restrictions or intense exercise regimens. Each participant’s body composition, serum concentrations of albumin and rapid turnover proteins including transthyretin and transferrin, BTR, and thyroid function were assessed.

Results

Compared to the controls, the athletes had significantly higher skeletal muscle index (SMI) (p < 0.001), and lower serum albumin concentration (p < 0.001) and BTR (p < 0.001). Kruskal–Wallis tests showed that serum albumin concentration and BTR were significantly lower in the participants with higher SMI. Serum albumin concentration and BTR were inversely correlated with SMI by multiple regression analysis (logarithmic albumin, β = − 0.358, p < 0.001; BTR, β = − 0.299, p = 0.001). SMI was inversely and transthyretin was positively correlated with serum albumin (SMI, β = − 0.554, p < 0.001; transthyretin, β = 0.379, p < 0.001). Serum concentration of free 3,5,3′-triiodothyronine (FT3) was inversely correlated with BTR, and, along with SMI and albumin, was independent predictor of BTR (SMI, β = − 0.321, p < 0.001; FT3, β = − 0.253, p = 0.001; logarithmic albumin, β = 0.261, p = 0.003). However, FT3 was not correlated with SMI or serum albumin. Serum concentrations of rapid turnover proteins were not correlated with BTR.

Conclusions

Increased skeletal muscle mass enhances the circulating amino acid imbalances, and is independently facilitated by thyroid hormones. Serum BTR may be a useful biomarker to assess the hypermetabolic state of wrestling athletes with high levels of skeletal muscle.
The degree of microsatellite instability predicts response to PD-1 blockade immunotherapy in mismatch repair-deficient/microsatellite instability-high colorectal cancers
Authors: Wang Qiao-Xuan , Qu Chun-Hua , Gao Yuan-Hong , Ding Pei-Rong , Yun Jing-Ping , Xie Dan , Cai Mu-Yan
Published: January 2021

The development of programmed cell death-1 inhibitor (PD-1) has shed light on the treatment of tumors with deficiencies in DNA mismatch repair system or microsatellite instability (dMMR/MSI). However, predicting the subset in this group that will benefit from PD-1 blockade remains a challenge. In this study, we aimed to investigate the relationship between the degree of microsatellite instability and the responses to anti-PD-1 immunotherapy. 33 patients with colorectal adenocarcinoma who had a known MSI status and received anti-PD-1 immunotherapy were included. PCR results for MSI of the whole cohort were collected and treatment response was evaluated. Our data indicated that objective response rate (ORR) in instability-high group (instability loci ≥ 3) was significantly higher than ORR in instability-intermediate group (13/16 versus 6/17, P = 0.008). Besides, patients in instability-high group had significant longer progression-free survival (log-rank test, P = 0.004), and a significant increase in T lymphocyte infiltration and cytolytic activity in tumors. Future study might implement the intensity of microsatellite instability for more delicate selection for anti-PD-1 therapy in patient with dMMR/MSI-H tumors.
Has Bipolar Disorder become a predominantly female gender related condition? Analysis of recently published large sample studies
Authors: Dell’Osso Bernardo , Cafaro Rita , Ketter Terence A.
Published: January 2021

Bipolar Disorders (BD) are disabling and severe psychiatric disorders, commonly perceived as equally affecting both men and women. The prevalence of BD in the general population has been growing over the last decade, however, few epidemiological studies are available regarding BD gender distribution, leaving unanswered the question whether the often reported increment of BD diagnosis could be gender specific. In fact, BD in female patients can often be misdiagnosed as MDD, leaving such women non correctly treated for longer times than their male counterparts. From this perspective, we searched literature for large sample (> 1000 subjects) studies published in the last decade (2010 onward) on BD patients. We included ten large sample studies that reported the gender distribution of their samples, and we therefore analysed them. Our results show a higher preponderance of female patients in every sample and sub-sample of BDI and BDII, supporting our hypothesis of an increase in BD diagnosis in females. BD in women presents with higher rates of rapid cycling, depressive polarity and suicide attempts, characteristics of non inferior severity compared to males; prompt recognition and adequate treatment of BD is therefore crucial to reduce risks and improve quality of life of affected women. In this regard, our results could lead the way for national or international epidemiological studies with the aim of more accurately assessing gender-specific prevalence of BD.
Process data, the new frontier for assessment development: rich new soil or a quixotic quest?
Authors: Provasnik Stephen
Published: January 2021

This paper presents the concepts and observations in the author’s keynote address at the May 2019 “Opportunity versus Challenge: Exploring Usage of Log-File and Process Data in International Large-Scale Assessments” conference in Dublin, Ireland. This paper recaps briefly some key points that emerged at the December 2018 ETS symposium on process data in Washington, DC, and suggests some common terminology and concepts for facilitating future meaningful discussion. It then borrows some concepts from evolutionary biologists to take a critical look at process data and some of its ethical implications before turning to discuss major applications for and challenges of using process data and logfiles. The second half of this paper then maps out the terrain in which process data emerges as a “byproduct” of the shift from paper-and-pencil testing to digital-based assessments (DBA) and looks closely at how process data interacts with the development and operationalization of assessment systems. This interaction suggests new, fresh ways of improving national and international assessment system processes, and ultimately the measurement of cognitive skills, while venturing into the new frontiers opened with process data.
A patient-specific 3D model of the knee to compare the femoral rollback before and after total knee arthroplasty (TKA)
Authors: Mercader Alexandra , Röttinger Timon , Bigdeli Amir , Lüth Tim C. , Röttinger Heinz
Published: January 2021

Purpose

Total knee arthroplasty (TKA) is nowadays performed as a standard procedure on a large number of patients suffering from arthrosis. Replacing the knee joint causes changes in the geometry and kinematics of the knee, which are unique to each individual. This research focuses on the method to detect these changes after TKA and on the impact on the knee movement. This approach could reduce complications in patients with post-operative pain and reduce the number of revisions.

Methods

A 3D model of a patient’s knee was made by measuring the movement with a medically certified infrared stereo camera. This measurement was combined with the 3D model of the patient’s bones, previously segmented from the CT scan. This model is printed in 3D, one part being the mechanism that follows the movement of the patient, and the other part being the 3D copy of the femur and tibia bones. The knee replacement operation is performed directly on the model and the resulting rollback is being measured before and after TKA.

Results

We observe a difference in the rollback before and after TKA on the 3D printed model. The variation in size and shape of the femoral implant compared to the natural femur condyles is one of the reasons for the changes in the rollback effect. The rollback is half as large after the prosthesis insertion, which confirms the fact that the femoral prosthesis geometry influences the knee kinematics.

Conclusions

In this study, a first 3D model combining the patient-specific kinematic and the geometry of his bones has been constructed. This model allows the surgeon to validate the plan of the operation, but also to understand the problems and consequences generated by the prosthesis insertion. The rollback is one of the most important motion of the knee joint and this behavior could be quantified, providing comparative analysis of the knee joint before and after the operation. As a future study, the model could be used to analyse more parameters of the TKA such as the impact of different implantation methods.
Application of an economic calculator to determine the cost of porcine reproductive and respiratory syndrome at farm-level in 21 pig herds in Germany
Authors: Renken C. , Nathues C. , Swam H. , Fiebig K. , Weiss C. , Eddicks M. , Ritzmann M. , Nathues H.
Published: January 2021

Background

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) continues to be a major economic issue for the swine industry worldwide, not only due to acute outbreaks but also endemic infections. PRRS disease severity and consequently financial losses can vary greatly between endemically infected farms and estimation of damage is challenging. This study aimed to assess the economic effect of PRRS in a systematic way at individual farm-level for endemically infected herds, using a PRRS cost simulation tool. In total 21 German sow herds with endemic PRRSV infection were investigated. Data on health and production performance, farm management and environment to be fed into the calculator was collected on each farm, and blood samples taken to confirm the PRRSV status.

Results

All study farms experienced a significant loss attributable to PRRS. The median farm budget across all farms was − 31 € per sow and year, compared to a median simulated farm budget of 248 € if these farms had been PRRSV negative. The median total loss attributable to PRRS was 74,181 € per farm per year, corresponding to a median total loss per sow and year of 255 €. The impact of PRRS on farm profits was − 19.1% on average and − 41% in the worst case.

Conclusions

The calculated losses give a good hint of the economic damage due to PRRS for the pig industry. Even in endemically infected farms, farmers face a non-negligible damage and profit from a concerted PRRS control. The calculator has proven itself in the field to render a valid estimation of losses due to PRRS in endemically infected farms.
A case of eagle fern (Pteridium aquilinum) poisoning on a pig farm
Authors: Waret-Szkuta Agnès , Jégou Laura , Lucas Marie Noelle , Gaide Nicolas , Morvan Hervé , Martineau Guy-Pierre
Published: January 2021

Background

Free-range pig farming represents a minor proportion of pig production in France but is attracting an increasing number of farmers because of societal expectations and the opportunity to use pasture-grazed forage. However, this type of farming faces several challenges, including biosecurity, parasitic management, and contact with wild fauna and pathogenic flora.

Case presentation

Two Gascon pigs raised on an outdoor fattening farm in the Hautes-Pyrenees department of France were submitted after sudden death for necropsy at the National Veterinary School of Toulouse. The pigs were of two different breeds but from the same group of 85 animals that had grazed on a 4-ha plot of land being used for grazing for the first time. Based on an in-depth interview with the farmer, the epidemiological information available, and the necropsy and histology examinations, a hypothesis of great eagle fern intoxication was proposed. Although the sample of animals available for diagnosis was small, the success of the administered therapy confirmed our diagnosis. It was recommended that in the short term, the animals be prevented access to the eagle fern by changing their pasture or removing the plants. Vitamin B1 and vitamin B6 were administered via feed as Ultra B® at 1 mL per 10 kg body weight per day for 2 days (providing 9 mg thiamine (vitamin B1) and 0.66 mg pyridoxine (vitamin B6) per kg body weight per day). Marked remission was observed, with 6 of 10 intoxicated animals with symptoms surviving (yielding a therapeutic success rate over 50%), but the therapy did not compensate for the loss of initial body condition. In total, of the 85 animals in the group after intoxication, 6 died, and 6 recovered.

Conclusions

The significance of this report lies in the scarcity of eagle fern intoxication cases reported in the literature, though such intoxication may become a significant problem as the development of outdoor rearing continues. Thus, eagle fern intoxication should be included in the differential diagnosis of nervous system symptoms in swine. The case also emphasizes the importance of anamnesis and discussion with the farmer as an essential step to guide diagnosis.
Balance Right in Multiple Sclerosis (BRiMS): a feasibility randomised controlled trial of a falls prevention programme
Authors: Gunn H. , Stevens K. N. , Creanor S. , Andrade J. , Paul L. , Miller L. , Green C. , Ewings P. , Barton A. , Berrow M. , Vickery J. , Marshall B. , Zajicek J. , Freeman J. A.
Published: January 2021

Background

Balance, mobility impairments and falls are problematic for people with multiple sclerosis (MS). The “Balance Right in MS (BRiMS)” intervention, a 13-week home and group-based exercise and education programme, aims to improve balance and minimise falls. This study aimed to evaluate the feasibility of undertaking a multi-centre randomised controlled trial and to collect the necessary data to design a definitive trial.

Methods

This randomised controlled feasibility study recruited from four United Kingdom NHS clinical neurology services. Patients ≥ 18 years with secondary progressive MS (Expanded Disability Status Scale 4 to 7) reporting more than two falls in the preceding 6 months were recruited. Participants were block-randomised to either a manualised 13-week education and exercise programme (BRiMS) plus usual care, or usual care alone.

Feasibility assessment evaluated recruitment and retention rates, adherence to group assignment and data completeness. Proposed outcomes for the definitive trial (including impact of MS, mobility, quality of life and falls) and economic data were collected at baseline, 13 and 27 weeks, and participants completed daily paper falls diaries.

Results

Fifty-six participants (mean age 59.7 years, 66% female, median EDSS 6.0) were recruited in 5 months; 30 randomised to the intervention group. Ten (18%) participants withdrew, 7 from the intervention group. Two additional participants were lost to follow up at the final assessment point. Completion rates were > 98% for all outcomes apart from the falls diary (return rate 62%).

After adjusting for baseline score, mean intervention—usual care between-group differences for the potential primary outcomes at week 27 were MS Walking Scale-12v2: − 7.7 (95% confidence interval [CI] − 17.2 to 1.8) and MS Impact Scale-29v2: physical 0.6 (CI − 7.8 to 9), psychological − 0.4 (CI − 9.9 to 9). In total, 715 falls were reported, rate ratio (intervention:usual care) for falls 0.81 (0.41 to 2.26) and injurious falls 0.44 (0.41 to 2.23).

Conclusions

Procedures were practical, and retention, programme engagement and outcome completion rates satisfied a priori progression criteria. Challenges were experienced in completion and return of daily falls diaries. Refinement of methods for reporting falls is therefore required, but we consider a full trial to be feasible.

Trial registration

ISRCTN13587999

Date of registration: 29 September 2016
A randomised controlled trial of energetic activity for depression in young people (READY): a multi-site feasibility trial protocol
Authors: Howlett N. , Bottoms L. , Chater A. , Clark A. B. , Clarke T. , David L. , Irvine K. , Jones A. , Jones J. , Mengoni S. E. , Murdoch J. , Pond M. , Sharma S. , Sims E. J. , Turner D. A. , Wellsted D. , Wilson J. , Wyatt S. , Trivedi D.
Published: January 2021

Background

Prevalence of depression is increasing in young people, and there is a need to develop and evaluate behavioural interventions which may provide benefits equal to or greater than talking therapies or pharmacological alternatives. Exercise could be beneficial for young people living with depression, but robust, large-scale trials of effectiveness and the impact of exercise intensity are lacking. This study aims to test whether a randomised controlled trial (RCT) of an intervention targeting young people living with depression is feasible by determining whether it is possible to recruit and retain young people, develop and deliver the intervention as planned, and evaluate training and delivery.

Methods

The design is a three-arm cluster randomised controlled feasibility trial with embedded process evaluation. Participants will be help-seeking young people, aged 13–17 years experiencing mild to moderate low mood or depression, referred from three counties in England. The intervention will be delivered by registered exercise professionals, supported by mental health support workers, twice a week for 12 weeks. The three arms will be high-intensity exercise, low-intensity exercise, and a social activity control. All arms will receive a ‘healthy living’ behaviour change session prior to each exercise session and the two exercise groups are energy matched. The outcomes are referral, recruitment, and retention rates; attendance at exercise sessions; adherence to and ability to reach intensity during exercise sessions; proportions of missing data; adverse events, all measured at baseline, 3, and 6 months; resource use; and reach and representativeness.

Discussion

UK National Health Service (NHS) policy is to provide young people with advice about using exercise to help depression but there is no evidence-based exercise intervention to either complement or as an alternative to medication or talking therapies. UK National Institute for Health and Care Excellence (NICE) guidelines suggest that exercise can be an effective treatment, but the evidence base is relatively weak. This feasibility trial will provide evidence about whether it is feasible to recruit and retain young people to a full RCT to assess the effectiveness and cost-effectiveness of an exercise intervention for depression.

Trial registration

ISRCTN,ISRCTN66452702. Registered 9 April 2020.
A mixed methods pilot randomised controlled trial to develop and evaluate the feasibility of a Mediterranean diet and lifestyle education intervention ‘THINK-MED’ among people with cognitive impairment
Authors: McGrattan Andrea M. , McEvoy Claire T. , Vijayakumar Aswathy , Moore Sarah E. , Neville Charlotte E. , McGuinness Bernadette , McKinley Michelle C. , Woodside Jayne V.
Published: January 2021

Background

Accumulating evidence supports the role of a Mediterranean diet (MD) in cognition, with a greater adherence to a MD associated with reduced dementia risk. It is important to understand how best to achieve behaviour change towards a MD, particularly in non-Mediterranean and high-risk populations. The aim of this study was to evaluate the feasibility of a MD and lifestyle education intervention (THINK-MED) among older adults with cognitive impairment.

Methods

Qualitative interviews (Phase I), conducted with mild cognitive impairment (MCI) participants, evaluated the intervention materials to allow refinement before pilot testing. THINK-MED was a 12-month, pilot RCT (Phase II) whereby MCI participants were randomised into one of three groups: education on one occasion vs education staged and supported by a dietitian vs control. The primary outcome was a change in MD score. Secondary outcome measurements were collected to gather data on variability of the outcomes to inform a full trial power calculation and to test their acceptability. Slower recruitment rates necessitated a change in primary outcome to a revised focus primarily on feasibility. A sub-study of the same THINK-MED intervention and data collection measures was also conducted among community-dwelling participants with subjective cognitive impairment (SCI) (NCT03569319).

Results

A total of 20 participants (n = 15 MCI; n = 5 SCI) were enrolled in the THINK-MED study. However, there were 10 (50%) participants (n = 9 MCI; n = 1 SCI) who withdrew from the study. Although, those who remained in the intervention rated and evaluated their experience as generally positive, recruitment and retention, especially from a MCI population, was extremely challenging. This highlights the complex needs of this heterogeneous clinical cohort. Recruiting participants from a community-based sample with SCI was more feasible, reaching a wider audience in a shorter time period. There were challenges relating to data collection and incompleteness, with the occurrence of missing data particularly among the questionnaire-based assessments.

Conclusions

Owing to the challenges with recruitment and retention of older adults with cognitive impairment in this study, it is difficult to confirm if this intervention is feasible. This research has highlighted considerations for a future trial, including a review of the recruitment strategies used and prioritisation of the outcome measures assessed.

Trial registration

Clinical trials registration NCT03265522/NCT03569319
Topical application of adipose tissue-derived mesenchymal stem cells (ADMSCs) reduced cerebral edema in experimental traumatic brain injury (TBI)—a preliminary study
Authors: Ma Hui , Cui Lian Xu , Lam Ping Kuen , Tong Cindy S. W. , Lo Kin K. Y. , Wong George K. C. , Poon Wai Sang
Published: January 2021

Background

Our previous studies showed that topical application of mesenchymal stem cells (MSCs) improved functional recovery in rat traumatic brain injury (TBI) model, and hypoxic precondition further enhanced the therapeutic effects of MSCs. There was no previous study on the attenuation of cerebral edema by MSCs.

We investigated whether topical application of normoxic and hypoxic MSCs could reduce cerebral edema in an experimental TBI model.

Methods

Two million normoxic (N = 24) and hypoxic (N = 24) MSCs were applied topically to exposed the cerebral cortex in a controlled cortical impact (CCI) model. The MSCs were fixed in position with fibrin glue. No treatment was given to control animals (TBI only: n = 24). After surgery, four animals in each group were sacrificed daily (day 1 to day 6) for edema evaluation. Normal animals without TBI were used as reference (n = 4). The expressions of GFAP, AQP4, and MMP9 were also investigated by immunofluorescence staining and RT-PCR at day 3.

Results

The edema peaked within 3 days after TBI. Compared with the control, hypoxic MSCs reduced brain water content significantly (p < 0.05). Both hypoxic and normoxic MSCs downregulated the expression of MMP9 and normalized AQP4 distribution to astrocyte end feet.

Conclusion

Our preliminary study showed that topical application of hypoxic MSCs suppressed both vasogenic and cytotoxic edema formation.
Endoscopically controlled surgery with open hemilaminectomy for the treatment of intradural extramedullary tumors: an operative technique and short-term outcomes of 20 consecutive cases
Authors: Yan Xiaorong , Wang Huiqing , Li Cai , Lin Yuanxiang , Lin Lin , Zhu Shinong , Wang Chenyang , Lin Zhangya , Jiang Changzhen , Kang Dezhi
Published: January 2021

Background

To present a surgical technique for the treatment of intradural extramedullary (IDEM) tumors by using endoscopically controlled surgery with open hemilaminectomy technique.

Methods

In this study, 20 patients with 22 IDEM tumors were enrolled. An endoscopically controlled surgery with open hemilaminectomy was employed to remove the tumors. Data related to clinical symptoms and medical images before and after surgery were collected for perioperative evaluation and follow-up analysis.

Results

All the tumors in 20 patients were well removed. The clinical symptoms were significantly reduced in all the patients as well. The short-term follow-up data showed that there was no tumor recurrence or spinal deformity.

Conclusion

The endoscopically controlled surgery with open hemilaminectomy technique provided favorable exposure and satisfactory resection to the IDEM tumors. It may be an effective surgical method for treating IDEM tumors. Larger samples and longer follow-up data are needed to verify its long-term effectiveness.
Mediators of SARS-CoV-2 entry are preferentially enriched in cardiomyocytes
Authors: Yang Jing , Chen Tan , Zhou Yafeng
Published: January 2021

Background

The coronavirus disease 2019 (COVID-19) has spread rapidly around the world. In addition to common respiratory symptoms such as cough and fever, some patients also have cardiac injury, however, the mechanism of cardiac injury is not clear. In this study, we analyzed the RNA expression atlases of angiotensin-converting enzyme 2(ACE2), cathepsin B (CTSB) and cathepsin L (CTSL) in the human embryonic heart at single-cell resolution.

Results

The results showed that ACE2 was preferentially enriched in cardiomyocytes. Interestingly, serine protease transmembrane serine protease 2 (TMPRSS2) had less expression in cardiomyocytes, but CTSB and CTSL, which belonged to cell protease, could be found to be enriched in cardiomyocytes. The results of enrichment analysis showed that differentially expressed genes (DEGs) in ACE2-positive cardiomyocytes were mainly enriched in the processes of cardiac muscle contraction, regulation of cardiac conduction, mitochondrial respiratory chain, ion channel binding, adrenergic signaling in cardiomyocytes and viral transcription.

Conclusions

Our study suggests that both atrial and ventricular cardiomyocytes are potentially susceptible to severe acute respiratory syndrome coronavirus-2(SARS-CoV-2), and SARS-CoV-2 may enter ventricular cardiomyocytes using CTSB/CTSL for S protein priming. This may be the partial cellular mechanism of cardiac injury in patients with COVID-19.
Unique hemoglobin dynamics in female Tibetan highlanders
Authors: Arima Hiroaki , Nakano Masayuki , Koirala Sweta , Ito Hiromu , Pandey Basu Dev , Pandey Kishor , Wada Takayuki , Yamamoto Taro
Published: January 2021

Background

Tibetan highlanders have adapted to hypoxic environments through the development of unique mechanisms that suppress an increase in hemoglobin (Hb) concentration even in high-altitude areas. Hb concentrations generally decrease with increasing age. However, in the highlands, chronic altitude sickness is known to occur in the elderly population. To investigate how aging in a hypoxic environment affects Hb levels in Tibetan highlanders, we focused on the Mustang people, who live above 3500 m. We tried to clarify the pure relationship between aging and Hb levels in a hypoxic environment.

Results

We found that the Hb concentration increased with increasing age in females but not in males. Multivariate analysis showed that age, pulse pressure, the poverty index, and vascular diameter were strongly correlated with the Hb concentration.

Conclusions

We found unique Hb dynamics among female Tibetan highlanders. As seen in these Hb dynamics, there may be sex-based differences in the adaptive mechanism in Tibetan highlanders.
Quality of sleep and associated factors among people living with HIV/AIDS on follow up at Ethiopian Zewditu memorial hospital, 2018
Authors: Mengistu Nebiyu , Azale Telake , Yimer Solomon , Fikreyesus Mahlet , Melaku Elsa , Shumye Seid
Published: January 2021

Background

Sleep disturbance is a common complaint in people living with HIV/AIDS. Despite the influence of sleep disturbance on treatment adherence, quality of life, work productivity, risk of chronic illness, it remains under-recognized and under-studied in Ethiopia. Therefore it is necessary to produce scientific evidence to fill the knowledge gap and areas of management. The current study aimed to assess sleep quality and its associated factors among people living with HIV/AIDS.

Methods

An institution-based cross-sectional study was utilized among 408 participants who were selected by a systematic random sampling technique at Zewditu memorial hospital from April to May 2018. The Pittsburgh Sleep Quality Index questionnaire was used to measure sleep quality. Ethical clearance was obtained from the joint ethics committee of the University of Gondar and Amanuel Mental Specialized Hospital. Oral informed consent was obtained from each participant. Binary and multivariable logistic regression models were fitted. Odds ratios (OR) with the corresponding 95% confidence interval (95%CI) was computed.

Results

The magnitude of poor sleep quality was 55.6%. Being female [AOR = 3.40, 95% CI: (1.80, 6.41)], depression [AOR =3.52, 95% CI: (1.95, 6.32)], CD4count ≤ 200 cells/mm3 [AOR = 3.18,95%CI: (1.65,6.13)], duration of HIV/AIDS diagnosis [AOR = 3.43,95% CI: (1.61,7.29)], current use of tobacco [AOR = 5.69, 95% CI: (2.04,15.9)] and chat or caffeinated drinks [AOR = 2.65, 95% CI: (1.06,6.64)] and poor sleep hygiene [AOR = 3.55, 95% CI: (1.85, 6.78)] were significantly associated with poor sleep quality.

Conclusions

More than half of the study participants were found to have poor sleep quality. A range factors influence quality of sleep of people with HIV/AIDS. Routine screening of sleep condition among people living with HIV/AIDS and early intervention based on the findings is suggested.
An English-language adaptation and validation of the Political Efficacy Short Scale (PESS)
Authors: Groskurth Katharina , Nießen Désirée , Rammstedt Beatrice , Lechner Clemens M.
Published: January 2021

The Political Efficacy Short Scale (PESS) is the English-language adaptation of the German-language Political Efficacy Kurzskala (PEKS); it measures perceived political efficacy with four items. PESS comprises two subscales—internal and external political efficacy—with two items each. Internal political efficacy refers to the belief in one’s own political effectiveness; external political efficacy refers to the belief in the responsiveness of the political system to citizens’ concerns. Completion time for all four items is less than 30 s. The items of the German-language source version were translated into English using the TRAPD approach. The present study empirically validated the English-language adaptation (PESS) based on a heterogeneous quota sample in the UK. The results show that the reliability and validity coefficients of the English-language adaptation are sufficiently high and that they are comparable to those of the German-language source version. In addition, the scale showed strict measurement invariance (i.e., equal loadings, intercepts, and uniquenesses) when comparing the UK and Germany, which indicates the comparability of manifest scale scores (means and variances) and correlations across the two nations. As a short scale, PESS lends itself particularly to the measurement of political efficacy in survey contexts in which assessment time or questionnaire space is limited. It is applicable in a variety of research disciplines, including political science, sociology, psychology, and economics.
A novel KCNH2 frameshift mutation (c.46delG) associated with high risk of sudden death in a family with congenital long QT syndrome type 2
Authors: Yoo Hyun Sok , Medina Nancy , von Wulffen María Alejandra , Ciampi Natalia , Paolucci Analia , Garro Hugo Ariel , Principato Mario Bruno , Acunzo Rafael Salvador , Carbajales Justo
Published: January 2021

Background

The congenital long QT syndrome type 2 is caused by mutations in KCNH2 gene that encodes the alpha subunit of potassium channel Kv11.1. The carriers of the pathogenic variant of KCNH2 gene manifest a phenotype characterized by prolongation of QT interval and increased risk of sudden cardiac death due to life-threatening ventricular tachyarrhythmias.

Results

A family composed of 17 members with a family history of sudden death and recurrent syncopes was studied. The DNA of proband with clinical manifestations of long QT syndrome was analyzed using a massive DNA sequencer that included the following genes: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, ANK2, KCNJ2, CACNA1, CAV3, SCN1B, SCN4B, AKAP9, SNTA1, CALM1, KCNJ5, RYR2 and TRDN. DNA sequencing of proband identified a novel pathogenic variant of KCNH2 gene produced by a heterozygous frameshift mutation c.46delG, pAsp16Thrfs*44 resulting in the synthesis of a truncated alpha subunit of the Kv11.1 ion channel. Eight family members manifested the phenotype of long QT syndrome. The study of family segregation using Sanger sequencing revealed the identical variant in several members of the family with a positive phenotype.

Conclusions

The clinical and genetic findings of this family demonstrate that the novel frameshift mutation causing haploinsufficiency can result in a congenital long QT syndrome with a severe phenotypic manifestation and an elevated risk of sudden cardiac death.