bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adipose-derived stem cells alleviate liver injury induced by type 1 diabetes mellitus by inhibiting mitochondrial stress and attenuating inflammation
Authors: Hou Yanli , Ding Wenyu , Wu Peishan , Liu Changqing , Ding Lina , Liu Junjun , Wang Xiaolei 
Published: April 2022

Abstract
Background
Type 1 diabetes mellitus (T1D) is a worldwide health priority due to autoimmune destruction and is associated with an increased risk of multiorgan complications. Among these complications, effective interventions for liver injury, which can progress to liver fibrosis and hepatocellular carcinoma, are lacking. Although stem cell injection has a therapeutic effect on T1D, whether it can cure liver injury and the underlying mechanisms need further investigation.

Methods
Sprague–Dawley rats with streptozotocin (STZ)-induced T1D were treated with adipose-derived stem cell (ADSC) or PBS via the tail vein formed the ADSC group or STZ group. Body weights and blood glucose levels were examined weekly for 6 weeks. RNA-seq and PCR array were used to detect the difference in gene expression of the livers between groups.

Results
In this study, we found that ADSCs injection alleviated hepatic oxidative stress and injury and improved liver function in rats with T1D; potential mechanisms included cytokine activity, energy metabolism and immune regulation were potentially involved, as determined by RNA-seq. Moreover, ADSC treatment altered the fibroblast growth factor 21 (FGF21) and transforming growth factor β (TGF-β) levels in T1D rat livers, implying its repair capacity. Disordered intracellular energy metabolism, which is closely related to mitochondrial stress and dysfunction, was inhibited by ADSC treatment. PCR array and ingenuity pathway analyses suggested that the ADSC-induced suppression of mitochondrial stress is related to decreased necroptosis and apoptosis. Moreover, mitochondria-related alterations caused liver inflammation, resulting in liver injury involving the T lymphocyte-mediated immune response.

Conclusions
Overall, these results improve our understanding of the curative effect of ADSCs on T1D complications: ADSCs attenuate liver injury by inhibiting mitochondrial stress (apoptosis and dysfunctional energy metabolism) and alleviating inflammation (inflammasome expression and immune disorder). These results are important for early intervention in liver injury and for delaying the development of liver lesions in patients with T1D.
Return to work after cell transplantation in patients with angiitis-induced critical limb ischaemia and factors related: a single-centre retrospective cohort study
Authors: Liu Hao , Liu Yifan , Pan Tianyue , Fang Yuan , Fang Gang , Jiang Xiaolang , Chen Bin , Wei Zheng , Gu Shiyang , Liu Peng , Fu Weiguo , Dong Zhihui 
Published: April 2022

Abstract
Background
Angiitis-induced critical limb ischaemia (AICLI) patients, who are usually young and have a high amputation rate, always lose their ability to return to the labour force. Return to work (RTW) not only indicates patients’ physical health, showing that they could undertake the work, but also demonstrates their psychological well-being. While cell transplantation showed satisfactory efficacy in limb salvage, few studies of AICLI patients’ RTW after transplantation have been reported.

Methods
From May 2009 to May 2021, AICLI patients who underwent cell transplantation and completed no less than 12 months of follow-up were retrospectively enrolled. The primary endpoint was RTW. Patient demographics and characteristics of the ischaemic limbs were reviewed to analyse independent risk factors for RTW.

Results
A total of 171 AICLI patients (170 males) were enrolled with a mean age of 41.9 ± 9.6 years (range: 20–57 years). The 12-month and 24-month RTW cumulative rates were 69.4% (95% confidence interval [CI] 61.6–75.6%) and 70.1% (95% CI 62.3–76.2%), respectively. Age < 40 years (odds ratio [OR] 2.659, 95% CI 1.138–6.719) and preoperative occupation as a mental worker (OR 8.930, 95% CI 2.665–42.847) were identified as independent protective factors for RTW. Perioperative limb infection with ulcer or gangrene (OR 0.250, 95% CI 0.075–0.779) was identified as an independent risk factor.

Conclusion
AICLI patients who underwent cell transplantation usually had a satisfactory midterm RTW cumulative rate. AICLI patients < 40 years old with preoperative occupation as mental workers were more likely to return to work. Prevention of limb infection during the perioperative period is of great significance to RTW.
Chaperone-mediated autophagy plays an important role in regulating retinal progenitor cell homeostasis
Authors: Jin Caixia , Ou Qingjian , Chen Jie , Wang Tao , Zhang Jieping , Wang Zhe , Wang Yuanyuan , Tian Haibin , Xu Jing-Ying , Gao Furong , Wang Juan , Li Jiao , Lu Lixia , Xu Guo-Tong 
Published: April 2022

AbstractPurposeTo explore the function and regulatory mechanism of IFITM3 in mouse neural retinal progenitor cells (mNRPCs), which was found to be very important not only in the development of the retina in embryos but also in NRPCs after birth.MethodsPublished single-cell sequencing data were used to analyze IFITM3 expression in mNRPCs. RNA interference was used to knock down the expression of IFITM3. CCK-8 assays were used to analyze cell viability. RNA-seq was used to assess mRNA expression, as confirmed by real-time quantitative PCR, and immunofluorescence assays and western blots were used to validate the levels of relative proteins, and autophagy flux assay. Lysosomal trackers were used to track the organelle changes.ResultsThe results of single-cell sequencing data showed that IFITM3 is highly expressed in the embryo, and after birth, RNA-seq showed high IFITM3 expression in mNRPCs. Proliferation and cell viability were greatly reduced after IFITM3 was knocked down. The cell membrane system and lysosomes were dramatically changed, and lysosomes were activated and evidently agglomerated in RAMP-treated cells. The expression of LAMP1 was significantly increased with lysosome agglomeration after treatment with rapamycin (RAMP). Further detection showed that SQSTM1/P62, HSC70 and LAMP-2A were upregulated, while no significant difference in LC3A/B expression was observed; no autophagic flux was generated.ConclusionIFITM3 regulates mNRPC viability and proliferation mainly through chaperone-mediated autophagy (CMA) but not macroautophagy (MA). IFITM3 plays a significant role in maintaining the homeostasis of progenitor cell self-renewal by sustaining low-level activation of CMA to eliminate deleterious factors in cells.
Safety of DW-MSC infusion in patients with low clinical risk COVID-19 infection: a randomized, double-blind, placebo-controlled trial
Authors: Karyana Muhammad , Djaharuddin Irawaty , Rif’ati Lutfah , Arif Mansyur , Choi Mi Kyung , Angginy Nova , Yoon Aeri , Han Jumi , Josh Fonny , Arlinda Dona , Narulita Asvin , Muchtar Faisal , Bakri Rizki Auliah , Irmansyah s 
Published: April 2022

AbstractBackgroundDue to their immunomodulatory properties, mesenchymal stem cells (MSCs) have been proposed to have therapeutic potential to improve clinical outcomes in COVID-19. However, the safety and efficacy profile of MSC infusion therapy in patients with non-severe COVID-19 infection has not been completely established; there is, in particular, a substantial void in the literature on dose-dependent studies of MSC infusion in patients with low clinical risk COVID-19 infection.MethodsThis phase 1 double-blind, placebo-controlled, randomized clinical trial examines the safety, feasibility, and tolerability of 2 doses (high and low) of DW-MSC in patients with low clinical risk COVID-19. A total of 9 patients were enrolled in this study and randomized into low-dose (TL), high-dose (TH), and placebo (C) groups. Subjects in the TL and TH groups received single intravenous infusions of 5.0 × 107cells and 1.0 × 108cells, respectively. The main outcome was the occurrence of treatment-emergent adverse events (TEAE) during the 28-day study period. Vital signs and various inflammatory markers were also monitored weekly during the observation period.ResultsThere were no apparent differences in clinical characteristics between study groups (TL, TH, and C) at baseline. All patients did not show the progression of severity during the study period. During the course of the study, 6 episodes of TEAE were observed in 5 subjects; however, none of the TEAEs were severe. During the follow-up period, 8 subjects recovered and were discharged from the hospital without complications. A subject exhibited abnormal liver function biomarkers at the end of the study period. Changes in inflammatory markers throughout the clinical course were not vastly different across study groups.ConclusionsOur clinical trial has provided reliable results regarding the safety of MSCs in low clinical risk COVID-19 subjects treated with MSCs. However, further confirmation of the therapeutic efficacy aspects of MSC will require large-scale randomized controlled trials in subjects with varying severity profiles for COVID-19.Trial registrationClinicalTrials.gov, NCT04535856. Registered 2 September 2020,https://clinicaltrials.gov/ct2/show/NCT04535856
Histone chaperone HIRA complex regulates retrotransposons in embryonic stem cells
Authors: Zhang Miao , Zhao Xin , Feng Xiao , Hu Xiao , Zhao Xuan , Lu Wange , Lu Xinyi 
Published: April 2022

Abstract
Background
Histone cell cycle regulator (HIRA) complex is an important histone chaperone that mediates the deposition of the H3.3 histone variant onto chromatin independently from DNA synthesis. However, it is still unknown whether it participates in the expression control of retrotransposons and cell fate determination.

Methods
We screened the role of HIRA complex members in repressing the expression of retrotransposons by shRNA depletion in embryonic stem cells (ESCs) followed by RT-qPCR. RNA-seq was used to study the expression profiles after depletion of individual HIRA member. RT-qPCR and western blot were used to determine overexpression of HIRA complex members. Chromatin immunoprecipitation (ChIP)-qPCR was used to find the binding of H3.3, HIRA members to chromatin. Co-immunoprecipitation was used to identify the interaction between Hira mutant and Ubn2. ChIP-qPCR was used to identify H3.3 deposition change and western blot of chromatin extract was used to validate the epigenetic change. Bioinformatics analysis was applied for the analysis of available ChIP-seq data.

Results
We revealed that Hira, Ubn2, and Ubn1 were the main repressors of 2-cell marker retrotransposon MERVL among HIRA complex members. Surprisingly, Ubn2 and Hira targeted different groups of retrotransposons and retrotransposon-derived long noncoding RNAs (lncRNAs), despite that they partially shared target genes. Furthermore, Ubn2 prevented ESCs to gain a 2-cell like state or activate trophectodermal genes upon differentiation. Mechanistically, Ubn2 and Hira suppressed retrotransposons by regulating the deposition of histone H3.3. Decreased H3.3 deposition, that was associated with the loss of Ubn2 or Hira, caused the reduction of H3K9me2 and H3K9me3, which are known repressive marks of retrotransposons.

Conclusions
Overall, our findings shed light on the distinct roles of HIRA complex members in controlling retrotransposons and cell fate conversion in ESCs.
Systemic evolutionary chemical space exploration for drug discovery
Authors: Lu Chong , Liu Shien , Shi Weihua , Yu Jun , Zhou Zhou , Zhang Xiaoxiao , Lu Xiaoli , Cai Faji , Xia Ning , Wang Yikai 
Published: April 2022

AbstractChemical space exploration is a major task of the hit-finding process during the pursuit of novel chemical entities. Compared with other screening technologies, computational de novo design has become a popular approach to overcome the limitation of current chemical libraries. Here, we reported a de novo design platform named systemic evolutionary chemical space explorer (SECSE). The platform was conceptually inspired by fragment-based drug design, that miniaturized a “lego-building” process within the pocket of a certain target. The key to virtual hits generation was then turned into a computational search problem. To enhance search and optimization, human intelligence and deep learning were integrated. Application of SECSE against phosphoglycerate dehydrogenase (PHGDH), proved its potential in finding novel and diverse small molecules that are attractive starting points for further validation. This platform is open-sourced and the code is available at http://github.com/KeenThera/SECSE.
In vivo vesicular acetylcholine transporter density in human peripheral organs: an [18F]FEOBV PET/CT study
Authors: Horsager Jacob , Okkels Niels , Van Den Berge Nathalie , Jacobsen Jan , Schact Anna , Munk Ole Lajord , Vang Kim , Bender Dirk , Brooks David J. , Borghammer Per 
Published: April 2022

Abstract
Background
The autonomic nervous system is frequently affected in some neurodegenerative diseases, including Parkinson’s disease and Dementia with Lewy bodies. In vivo imaging methods to visualize and quantify the peripheral cholinergic nervous system are lacking. By using [18F]FEOBV PET, we here describe the peripheral distribution of the specific cholinergic marker, vesicular acetylcholine transporters (VAChT), in human subjects. We included 15 healthy subjects aged 53–86 years for 70 min dynamic PET protocol of peripheral organs. We performed kinetic modelling of the adrenal gland, pancreas, myocardium, renal cortex, spleen, colon, and muscle using an image-derived input function from the aorta. A metabolite correction model was generated from venous blood samples. Three non-linear compartment models were tested. Additional time-activity curves from 6 to 70 min post injection were generated for prostate, thyroid, submandibular-, parotid-, and lacrimal glands.

Results
A one-tissue compartment model generated the most robust fits to the data. Total volume-of-distribution rank order was: adrenal gland > pancreas > myocardium > spleen > renal cortex > muscle > colon. We found significant linear correlations between total volumes-of-distribution and standard uptake values in most organs.

Conclusion
High [18F]FEOBV PET signal was found in structures with known cholinergic activity. We conclude that [18F]FEOBV PET is a valid tool for estimating VAChT density in human peripheral organs. Simple static images may replace kinetic modeling in some organs and significantly shorten scan duration.
Clinical Trial Registration Trial registration: NCT, NCT03554551. Registered 31 May 2018. https://clinicaltrials.gov/ct2/show/NCT03554551?term=NCT03554551&draw=2&rank=1.
Measuring disability-adjusted life years (DALYs) due to COVID-19 in Scotland, 2020
Authors: Wyper Grant M. A. , Fletcher Eilidh , Grant Ian , McCartney Gerry , Fischbacher Colin , Harding Oliver , Jones Hannah , de Haro Moro Maria Teresa , Speybroeck Niko , Devleesschauwer Brecht , Stockton Diane L. 
Published: April 2022

AbstractBackgroundDisability-adjusted life years (DALYs) combine the impact of morbidity and mortality and can enable comprehensive, and comparable, assessments of direct and indirect health harms due to COVID-19. Our aim was to estimate DALYs directly due to COVID-19 in Scotland, during 2020; and contextualise its population impact relative to other causes of disease and injury.MethodsNational deaths and daily case data were used. Deaths were based on underlying and contributory causes recorded on death certificates. We calculated DALYs based on the COVID-19 consensus model and methods outlined by the European Burden of Disease Network. DALYs were presented as a range, using a sensitivity analysis based on Years of Life Lost estimates using: cause-specific; and COVID-19 related deaths. All COVID-19 estimates were for 2020.ResultsIn 2020, estimates of COVID-19 DALYs in Scotland ranged from 96,500 to 108,200. Direct COVID-19 DALYs were substantial enough to be framed as the second leading cause of disease and injury, with only ischaemic heart disease having a larger impact on population health. Mortality contributed 98% of total DALYs.ConclusionsThe direct population health impact of COVID-19 has been very substantial. Despite unprecedented mitigation efforts, COVID-19 developed from a single identified case in early 2020 to a condition with an impact in Scotland second only to ischaemic heart disease. Periodic estimation of DALYs during 2021, and beyond, will provide indications of the impact of DALYs averted due to the national rollout of the vaccination programme and other continued mitigation efforts, although new variants may pose significant challenges.
Does food security exist among farm households? Evidence from Ghana
Authors: Acheampong Patricia Pinamang , Obeng Elvis Agyei , Opoku Monica , Brobbey Lydia , Sakyiamah Bernard 
Published: April 2022

Abstract
Background
Food security exists when households have physical, social and economic access to sufficient, safe and nutritious food at all times that meets their dietary needs and food preferences for an active and healthy life. Food security remains a serious challenge for many households in Ghana and the situation is even more prevalent among smallholder farmers. Therefore, this study had its objectives to assess food security status and also estimate their determinants for policy recommendations.

Methodology
Using data collected from 2,603 farm households across Ghana and employing an ordered probit model the determinants of food security among farm households were assessed. The food security indicator, Food Consumption Score (FCS) which combines diet diversity, frequency of consumption and relative nutritional importance of different food groups was used to determine food security status of farm households.

Results
Results showed that farm households (76%) across Ghana were within the acceptable household food consumption groups. Nonetheless, 19% and 6% of farm households, respectively, were within the borderline and poor food consumption groups, respectively. Determinants of food security included experience, gender, improved variety adoption, access to credit and location.

Conclusion
Food security risk is prevalent among farm households in Ghana. Based on the results on determinants of food security, the suggestions are that government and private institutions should create an enabling environment to enhancing credit access and encouraging adoptions of improved crops varieties for increased production.
Personality metatraits predict resilience among family caregivers responsible for a dependent youth’s chronic respiratory management
Authors: Dong Sidai , Elliott Timothy R. , Luo Wen , Warren Ann Marie , Warren Robert 
Published: April 2022

Abstract
Background
Family caregivers of children and youth with severe neurodisabilities that require chronic respiratory management often report a compromised quality of life. In this cross-sectional study, we used DeYoung’s (Psychol Inq 21(1): 26–33, 2010. 10.1080/10478401003648674) conceptualization of two personality metatraits, Alpha and Beta, to test their theorized role in facilitating resilience among these family caregivers. We expected higher Alpha and Beta would exhibit direct, beneficial effects on caregiver mental and physical health quality of life (QoL), and they would operate through self-reported resilience and coping to exert positive, indirect effects on caregiver QoL.

Methods
Family caregivers of children and youth at an outpatient chronic respiratory management clinic were informed of the study. Of the 68 who consented, 61 provided complete data on measures of personality traits, coping styles, and physical and mental health-related QoL. Factor analytic techniques verified the two personality metatraits, consistent with the DeYoung model. The metatraits were then used as predictor variables in a path model to predict physical and mental health-related QoL. Self-reported resilience and a coping variable were examined as possible mediators of the personality-QoL relationship.

Results
Correlational analyses isolated a coping variable that met criteria as a possible mediator. The path model exhibited good fit to the data. The Alpha metatrait—characterized by emotional stability, self-regulation, perseverance, and intrinsic motivation—was directly predictive of caregiver mental health. The Beta metatrait, reflecting a disposition for adaptive flexibility, responsiveness, and interpersonal initiative, demonstrated significant indirect effects to physical and mental health through its positive association with coping efforts to maintain social support and a sense of self.

Conclusions
Consistent with DeYoung’s conceptualization, higher Alpha and Beta predicted caregiver resilience, albeit through different pathways. The emotional stability, perseverance and emotional regulation associated with Alpha likely accounted for its positive association with caregiver mental health. Beta, in contrast, may operate through their adaptive flexibility, personal resourcefulness and social engagement to augment coping efforts that involve others and support family activities, which, in turn, promote their own physical and mental health. Limitations of the cross-sectional design, and potential theoretical and clinical implications of the personality metatraits and their relation to resilience are discussed.
Sperm DNA damage compromises embryo development, but not oocyte fertilisation in pigs
Authors: Mateo-Otero Yentel , Llavanera Marc , Recuero Sandra , Delgado-Bermúdez Ariadna , Barranco Isabel , Ribas-Maynou Jordi , Yeste Marc 
Published: April 2022

AbstractBackgroundThe assessment of sperm DNA integrity has been proposed as a complementary test to conventional mammalian semen analysis. In this sense, single-strand (SSB) and double-strand (DSB) DNA breaks, the two types of sperm DNA fragmentation (SDF), have been reported to have different aetiologies and to be associated to different fertility outcomes in bovine and humans. Considering that no studies in porcine have addressed how SDF may affect sperm quality and fertility outcomes, the present work aimed to determine the impact of global DNA damage, SSB and DSB on sperm quality and in vitro fertilising ability. To this end, 24 ejaculates (one per boar) were split into three aliquots: the first was used to assess sperm quality parameters through a computer-assisted sperm analysis (CASA) system and flow cytometry; the second was used to perform in vitro fertilisation, and the third, to evaluate sperm DNA integrity using alkaline and neutral Comet assays.ResultsThe results showed that global DNA damage negatively correlates (P < 0.05) with normal sperm morphology (R = − 0.460) and progressive motility (R = − 0.419), and positively with the percentage of non-viable sperm (R = 0.507). Multiple regression analyses showed that non-viable sperm were related to SSB (β = − 0.754). In addition, while fertilisation did not seem to be affected by sperm DNA integrity, global DNA damage, DSB and SSB were found to be correlated to embryo development outcomes. Specifically, whereas global DNA damage and DSB negatively affected (P < 0.05) the later preimplantation embryo stages (percentage of early blastocyst/blastocyst D6: for global DNA damage, R = − 0.458, and for DSB, R = − 0.551; and percentage of hatching/hatched blastocyst D6: for global DNA damage, R = − 0.505, and for DSB, R = − 0.447), global DNA damage and SSB had a negative impact (P < 0.05) on the developmental competency of fertilised embryos (R = − 0.532 and R = − 0.515, respectively). Remarkably, multiple regression analyses supported the associations found in correlation analyses. Finally, the present work also found that the inclusion of Comet assays to the conventional sperm quality tests improves the prediction of blastocyst formation (AUC = 0.9021,P < 0.05), but not fertilisation rates (P > 0.05).ConclusionConsidering all these findings, this work sets a useful model to study how SDF negatively influences fertility.