bluuebunny/crossref_metadata_2025_split huggingface dataset:
RETRACTED ARTICLE: HnRNP A1 - mediated alternative splicing of CCDC50 contributes to cancer progression of clear cell renal cell carcinoma via ZNF395
Authors: Sun Guoliang , Zhou Hui , Chen Ke , Zeng Jin , Zhang Yangjun , Yan Libin , Yao Weimin , Hu Junhui , Wang Tao , Xing Jinchun , Xiao Kefeng , Wu Lily , Ye Zhangqun , Xu Hua 
Published: June 2020

Abstract
Background
Aberrant alternative splicing events play critical roles in carcinogenesis and progression of many cancers, while sparse studies regarding to alternative splicing are available for clear cell renal cell carcinoma (ccRCC). We identified that alternative splicing of coiled-coil domain containing 50 (CCDC50) was dysregulated in ccRCC, whereas the clinical significance of this splicing event and its splicing regulation mechanisms were still elusive.

Methods
Bioinformatic algorithm was utilized to identify significant exon skipping events in ccRCC via exon sequencing data from The Cancer Genome Atlas. Semi-quantitative real-time polymerase chain reaction and western blot were used to validate the aberrant expression of different transcripts in renal cancer tissues, cell lines and corresponding noncancerous controls. Short hairpin RNA targeting CCDC50 and overexpressing plasmids for each transcript were introduced into ccRCC cell lines, followed by a series of in vitro and in vivo functional experiments. Moreover, a panel of splicing factors were identified and their roles on splicing regulation of CCDC50 precursor mRNA (pre-mRNA) were studied. Furthermore, RNAseq data were analyzed to elucidate downstream molecules of CCDC50. Two-way analysis of variance and unpaired Student t test were used in statistical analysis.

Results
Pre-mRNA of CCDC50 generated two transcripts, full-length transcript (CCDC50-FL) and truncated transcript (CCDC50-S) with exon 6 skipped. CCDC50-S was overexpressed in ccRCC tissues and cell lines compared to noncancerous counterparts, but CCDC50-FL was only detected in noncancerous tissues and normal renal epithelial cells. Higher percent spliced-in index was associated with better survival in ccRCC patients. In vitro and in vivo functional experiments indicated that CCDC50-S transcript promoted the proliferation, migration, invasion and tumorigenesis of ccRCC, while CCDC50-FL exerted opposite tumor suppressive functions. Besides, we identified that heterogeneous nuclear ribonucleoprotein A1 (HnRNP A1) could promote the skipping of exon 6, which resulted in higher portion of CCDC50-S and oncogenic transformation. Moreover, zinc finger protein 395 (ZNF395) was identified as a downstream protein of CCDC50-S, and the interaction initiated oncogenic pathways which were involved in ccRCC progression.

Conclusions
Aberrant alternative splicing of CCDC50 is regulated by HnRNP A1 in ccRCC. This splicing event contributes to cancer progression through the downstream pathway involving ZNF395.
The direct superior approach versus posterior approach for total hip arthroplasty: study protocol for a prospective double-blinded randomised control trial
Authors: Kayani Babar , Konan Sujith , Tahmassebi Jenni , Ayuob Atif , Haddad Fares S. 
Published: June 2020

AbstractBackgroundThe direct superior approach (DSA) is a minimally invasive modification of the posterior approach (PA) that preserves the iliotibial band and short external rotators except for the piriformis or conjoint tendon during total hip arthroplasty (THA). The objective of this study is to compare patient satisfaction, functional outcomes, accuracy of implant positioning, component stability, gait, cost-effectiveness, and complications in the DSA versus PA for THA.Methods and analysisThis prospective double-blinded randomised control trial will include 80 patients with symptomatic hip osteoarthritis undergoing primary THA. Following informed consent, patients will be randomised to THA using the PA (control group) or DSA (investigation group) at a ratio of 1:1 using an online random number generator. Blinded observers will review patients at regular intervals for 2 years after surgery to record predefined study outcomes relating to postoperative rehabilitation, clinical progress, functional outcomes, accuracy of implant positioning, gait analysis on force plate treadmill, implant migration with radiosteriometric analysis, cost-effectiveness, and complications. A superiority study design will be used to evaluate whether the DSA provides improved outcomes compared to the PA for THA. Evaluation of study outcomes in DSA and PA will be used to quantify and draw inferences on differences in the efficacy of treatment between the two groups. Intention-to-treat and per-protocol population analysis will be undertaken. The following statistical methods will be employed to analyse the data: descriptive statistics, independentttest, pairedttest, analysis of variance, Fisher exact test, chi-square test, and graphical displays. Ethical approval was obtained from the London-Fulham Research Ethics Committee, UK. The study is sponsored by University College London, UK.DiscussionThis study compares a comprehensive and robust range of clinical, functional, and radiological outcomes in THA performed using the PA versus DSA. The findings of this study will provide an improved understanding of the differences in the PA versus DSA for THA with respect to patient satisfaction, functional outcomes, implant survivorship, gait, cost-effectiveness, and complications.Trial registrationClinicalTrials.gov,NCT04191993. Registered on 10 December 2019
Efficacy and safety of Zihua Wenfei granules in treatment of postinfectious cough (wind-cold invading lungs syndrome): study protocol for a randomized controlled trial
Authors: Wang Huanan , She Bin , Mao Bing , Jiang Hongli 
Published: June 2020

AbstractBackgroundPostinfectious cough usually develops and persists following respiratory tract infection. The protracted cough is embarrassing and troublesome and significantly impairs daily life. However, the optimal treatment available for this condition is still not known. This study aims to investigate the efficacy and safety of a new Chinese herbal prescription, Zihua Wenfei granule (ZHWFG), in treatment of postinfectious cough (wind-cold invading lungs syndrome).MethodsThis study is a prospective, multi-center, randomized, double-blinded, parallel group, placebo-controlled trial. A total of 216 adult participants with postinfectious cough will be enrolled from six study centers across China. All participants are randomly allocated to one of three parallel treatment groups: (1) 15 g of active ZHWFG three times daily, (2) 10 g of active ZHWFG plus 5 g of ZHWFG-matched placebo three times daily, and (3) 15 g of ZHWFG-matched placebo three times daily. The treatment duration is 14 consecutive days. The primary outcomes are cough resolution rate and cough relief rate. Secondary outcomes include time to cough resolution, time to cough relief, change from baseline in cough symptom score, cough visual analog scale value, traditional Chinese medicine syndrome score at days 7 and 14, and change of CQLQ from baseline to post-treatment as well as adverse events.DiscussionThis trial may not only investigate the efficacy and safety of ZHWFG in the management of postinfectious cough (wind-cold invading lungs syndrome), but also add the evidence of Chinese herbal medicine in treatment of postinfectious cough and provide an alternative option for the management of postinfectious cough.Trial registrationChiCTR1900022078. Registered on 23 March 2019.http://www.chictr.org.cn/showproj.aspx?proj=36547.
Low UV-C stress modulates Chlamydomonas reinhardtii biomass composition and oxidative stress response through proteomic and metabolomic changes involving novel signalers and effectors
Authors: Colina Francisco , Carbó María , Meijón Mónica , Cañal María Jesús , Valledor Luis 
Published: June 2020

Abstract
Background
The exposure of microalgae and plants to low UV-C radiation dosages can improve their biomass composition and stress tolerance. Despite UV-C sharing these effects with UV-A/B but at much lower dosages, UV-C sensing and signal mechanisms are still mostly unknown. Thus, we have described and integrated the proteometabolomic and physiological changes occurring in Chlamydomonas reinhardtii—a simple Plantae model—into the first 24 h after a short and low-intensity UV-C irradiation in order to reconstruct the microalgae response system to this stress.

Results
The microalgae response was characterized by increased redox homeostasis, ROS scavenging and protein damage repair/avoidance elements. These processes were upregulated along with others related to the modulation of photosynthetic electron flux, carbon fixation and C/N metabolism. These changes, attributed to either direct UV-C-, ROS- or redox unbalances-associated damage, trigger a response process involving novel signaling intermediaries and effectors such as the translation modulator FAP204, a PP2A-like protein and a novel DYRK kinase. These elements were found linked to the modulation of Chlamydomonas biomass composition (starch accumulation) and proliferation, within an UV-C response probably modulated by different epigenetic factors.

Conclusion
Chosen multiomics integration approach was able to describe many fast changes, including biomass composition and ROS stress tolerance, as a response to a low-intensity UV-C stress. Moreover, the employed omics and systems biology approach placed many previously unidentified protein and metabolites at the center of these changes. These elements would be promising targets for the characterization of this stress response in microalgae and plants and the engineering of more productive microalgae strains.
Sex differences in Alzheimer’s-related Tau biomarkers and a mediating effect of testosterone
Authors: Sundermann Erin E. , Panizzon Matthew S. , Chen Xu , Andrews Murray , Galasko Douglas , Banks Sarah J. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2020

AbstractWomen show greater pathological Tau biomarkers than men along the Alzheimer’s disease (AD) continuum, particularly among apolipoprotein ε-E4 (APOE4) carriers; however, the reason for this sex difference in unknown. Sex differences often indicate an underlying role of sex hormones. We examined whether testosterone levels might influence this sex difference and the modifying role of APOE4 status. Analyses included 172 participants (25 cognitively normal, 97 mild cognitive impairment, 50 AD participants) from the Alzheimer’s Disease Neuroimaging Initiative (34% female, 54% APOE4 carriers, aged 55–90). We examined the separate and interactive effects of plasma testosterone levels and APOE4 on cerebrospinal fluid phosphorylated-tau181 (p-Tau) levels in the overall sample and the sex difference in p-Tau levels before and after adjusting for testosterone. A significant APOE4-by-testosterone interaction revealed that lower testosterone levels related to higher p-Tau levels among APOE4 carriers regardless of sex. As expected, women had higher p-Tau levels than men among APOE4 carriers only, yet this difference was eliminated upon adjustment for testosterone. Results suggest that testosterone is protective against p-Tau particularly among APOE4 carriers. The lower testosterone levels that typically characterize women may predispose them to pathological Tau, particularly among female APOE4 carriers.
Natural convection flow of a fluid using Atangana and Baleanu fractional model
Authors: Aman Sidra , Abdeljawad Thabet , Al-Mdallal Qasem 
Published: June 2020

AbstractA modified fractional model for the magnetohydrodynamic (MHD) flow of a fluid is developed utilizing Atangana–Baleanu fractional derivative (ABFD). Natural convection and wall oscillation instigate the flow over a vertical plate positioned in a porous medium. The partial differential equations (PDEs) are transmuted to ordinary differential equations (ODEs). The Laplace transform method with its inversion is employed to accomplish the exact solutions of momentum and heat equations. The final solution is expressed in terms of gamma function, modified Bessel function, and Mittag-Leffler function. The previous definitions Caputo fractional and Riemann–Liouville are rarely used by the researchers now due to their limitations. The newly introduced ABFD has got significance nowadays due to its nonlocal and nonsingular kernel. This work focuses on the oscillating boundary conditions for the viscous model in terms of ABFD. The influence of involved parameters is interpreted through plots. The velocity profile is an increasing function of fractional parameter and jumps for a higher Grashof number due to buoyancy push. Furthermore, the Atangana–Baleanu (AB) model is compared with the ordinary derivative model for limiting case and analyzed in detail. It is noted that the ordinary fluid flows faster compared to the fractional fluid.
Fungal statin pump protein improves monacolin J efflux and regulates its production in Komagataella phaffii
Authors: Bai Chenxiao , Liu Yiqi , Chen Xinjie , Qian Zhilan , Liu Haifeng , Zhou Xiangshan , Zhang Yuanxing , Cai Menghao 
Published: June 2020

Abstract
Background
Monacolin J (MJ) is a key intermediate for the synthesis of cholesterol-lowering drug simvastatin. Current industrial production of MJ involves complicated chemical hydrolysis of microbial fermented lovastatin. Recently, heterologous production of MJ has been achieved in yeast and bacteria, but the resulting metabolic stress and excessive accumulation of the compound adversely affect cell activity.

Results
Five genes, tapA, stapA, slovI, smokI and smlcE, coding for fungal statin pump proteins were expressed in an MJ producing yeast strain, Komagataella phaffii J#9. Overexpression of these genes facilitated MJ production. Among them, tapA from Aspergillus terreus highly improved MJ production and led to a titer increase of 108%. Exogenous MJ feeding study on an MJ non-producing strain GS-PGAP-TapA was then performed, and the results illustrated tough entry of MJ into cells and possible efflux action of TapA. Further, intracellular and extracellular MJ levels of J#9 and J#9-TapA were analyzed. The extracellular MJ level of J#9-TapA increased faster, but its intracellular MJ percentage kept lower as compared to J#9. The results proved that TapA effectively excreted MJ from cells. Then functions of TapA were evaluated in a high-production bioreactor fermentation. Differently, TapA expression caused a low MJ titer but high intracellular MJ accumulation in J#9-TapA compared with J#9.

Conclusions
Statin pump proteins improved MJ production in K. phaffii in a shake flask. Exogenous MJ feeding and endogenous MJ producing experiments demonstrated the efflux function of TapA. TapA improved MJ production at low MJ levels in a shake flask, but decreased it at high MJ levels in a bioreactor. This finding is useful for statin pump improvement and metabolic engineering for statin bioproduction.
Food insecurity among senior citizens in high out-migration areas: evidence from Western Nepal
Authors: Singh Devendra Raj , Ghimire Saruna , Jeffers Eva M. , Singh Sunita , Nath Dhirendra , Szabo Sylvia 
Published: June 2020

Abstract
Background
Food insecurity is a critical public health challenge, particularly in low- and middle-income countries such as Nepal. The demographic transition has resulted in a growing population of senior citizens. However, the determinants of food insecurity among Nepali senior citizens remain unknown. This study aims to fill this gap by assessing food insecurity among the older populations in the far-western region, one of the poorest regions of the country. Further, we also aim to assess the potential association between adult children’s migration and the food insecurity status of the left behind older parents.

Methods
A community-based cross-sectional study was conducted among 260 randomly selected senior citizens in the Kanchanpur district in far-western Nepal. The short form of the household food security scale, originally developed by the United States Department of Agriculture, was used to measure household food security. Associations were examined by logistic regression.

Results
The prevalence of food insecurity in senior citizens’ households was 41.1%. Senior citizen households with their adult children’s migration (AOR = 0.47, 95% CI: 0.24–0.95) had lower odds of being food insecure whereas households with lower family income (<$100 compared to ≥ $100) had two times higher odds of being food insecure (AOR = 2.26, 95% CI: 1.08–4.76). Also, households owning a cultivable land/farm (AOR = 0.14, 95% CI: 0.05–0.40), primary source of income as service/pension (AOR = 0.26, 95% CI: 0.08–0.89) or business (AOR = 0.15, 95% CI: 0.03–0.59) and participants who received geriatric allowances (AOR = 0.05, 95% CI = 0.01–0.16) had lower odds of being food insecure.

Conclusion
The prevalence of food insecurity among households with a senior citizen in Kanchanpur district was high and associated with the migration status of adult children, and household socioeconomic status. This calls for a greater policy response focused specifically on households with older adults and the integration of gerontological evidence into the existing food security and nutrition strategies.
A randomised feasibility study of computerised cognitive training as a therapeutic intervention for people with Huntington’s disease (CogTrainHD)
Authors: Yhnell Emma , Furby Hannah , Lowe Rachel S. , Brookes-Howell Lucy C. , Drew Cheney J. G. , Playle Rebecca , Watson Gareth , Metzler-Baddeley Claudia , Rosser Anne E. , Busse Monica E. 
Published: June 2020

AbstractBackgroundHuntington’s disease (HD) is associated with a range of cognitive deficits including problems with executive function. In the absence of a disease modifying treatment, cognitive training has been proposed as a means of slowing cognitive decline; however, the impact of cognitive training in HD patient populations remains unclear. The CogTrainHD study assessed the feasibility and acceptability of home-based computerised executive function training, for people impacted by HD.MethodsThirty HD gene carriers were recruited and randomised to either executive function training or non-intervention control groups. Participants allocated to the intervention group were asked to complete executive function training three times a week for 30 min for 12 weeks in their own homes. Semi-structured interviews were conducted with participants and friends, family or carers, to determine their views on the study.Results26 out of 30 participants completed the baseline assessments and were subsequently randomised: 13 to the control group and 13 to the intervention group. 23 of the 30 participants were retained until study completion: 10/13 in the intervention group and 13/13 in the control group. 4/10 participants fully adhered to the executive function training. All participants in the control group 13/13 completed the study as intended. Interview data suggested several key facilitators including participant determination, motivation, incorporation of the intervention into routine and support from friends and family members. Practical limitations, including lack of time, difficulty and frustration in completing the intervention, were identified as barriers to study completion.ConclusionsThe CogTrainHD feasibility study provides important evidence regarding the feasibility and acceptability of a home-based cognitive training intervention for people with HD. Variable adherence to the cognitive training implies that the intervention is not feasible to all participants in its current form. The study has highlighted important aspects in relation to both the study and intervention design that require consideration, and these include the design of games in the executive function training software, logistical considerations such as lack of time, the limited time participants had to complete the intervention and the number of study visits required. Further studies are necessary before computerised executive function training can be recommended routinely for people with HD.Trial registrationClinicalTrials.gov, Registry numberNCT02990676.
What makes it work? Exploring experiences of patient research partners and researchers involved in a long-term co-creative research collaboration
Authors: Hovén Emma , Eriksson Lars , Månsson D’Souza Åsa , Sörensen Johanna , Hill David , Viklund Carolin , Wettergren Lena , Lampic Claudia 
Published: June 2020

Abstract
Background
Exchanging experiences of patient and public involvement (PPI) can bring insights into why, how and when PPI is most effective. The aim of this study was to explore the experiences of patient research partners (PRPs) and researchers engaged in a co-creative long-term collaboration in cancer research.

Methods
The aim and procedures of this study were jointly decided upon by PRPs and researchers. The PRPs included former patients treated for cancer and significant others of the same target group. The participants (11 PRPs, 6 researchers) took part in semi-structured telephone interviews. The interviews were analysed using qualitative content analysis by a researcher who had no prior relationships with the participants.

Results
Five overarching categories were identified: Reasons for investing in a long-term collaboration, Benefits of participating, Improving the research, Elements of success and Challenges and ways to improve. Reasons for investing in the collaboration included the desire to improve cancer care and to make use of own negative experiences. Benefits of participating included a positive impact on the PRPs’ psychosocial adjustment to the illness. Moreover, the researchers highlighted that working together with the PRPs made the research feel more meaningful. The participants reported that the collaboration improved the relevance and acceptability of the research. Having a shared goal, a clear but yet accommodating structure, as well as an open and trustful working atmosphere were recognised as elements of success. The PRPs furthermore emphasized the importance of seeing that their input mattered. Among the few challenges raised were the distance to the meeting venues for some PRPs and a limited diversity among participants.

Conclusions
This study identified factors essential to researchers and clinicians attempting to engage the public in research. Our results suggest that for successful patient involvement, the purpose and format of the collaboration should be clear to both PRPs and researchers. A clear but yet accommodating structure and keen leadership emerged as key factors to create a sense of stability and a trustful atmosphere. Furthermore, providing regular feedback on how PRPs input is implemented is important for PRPs to stay committed over time.