bluuebunny/crossref_metadata_2025_split huggingface dataset:
A globally diverse reference alignment and panel for imputation of mitochondrial DNA variants
Authors: McInerney Tim W. , Fulton-Howard Brian , Patterson Christopher , Paliwal Devashi , Jermiin Lars S. , Patel Hardip R. , Pa Judy , Swerdlow Russell H. , Goate Alison , Easteal Simon , Andrews Shea J. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2021

Abstract
Background
Variation in mitochondrial DNA (mtDNA) identified by genotyping microarrays or by sequencing only the hypervariable regions of the genome may be insufficient to reliably assign mitochondrial genomes to phylogenetic lineages or haplogroups. This lack of resolution can limit functional and clinical interpretation of a substantial body of existing mtDNA data. To address this limitation, we developed and evaluated a large, curated reference alignment of complete mtDNA sequences as part of a pipeline for imputing missing mtDNA single nucleotide variants (mtSNVs). We call our reference alignment and pipeline MitoImpute.

Results
We aligned the sequences of 36,960 complete human mitochondrial genomes downloaded from GenBank, filtered and controlled for quality. These sequences were reformatted for use in imputation software, IMPUTE2. We assessed the imputation accuracy of MitoImpute by measuring haplogroup and genotype concordance in data from the 1000 Genomes Project and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The mean improvement of haplogroup assignment in the 1000 Genomes samples was 42.7% (Matthew’s correlation coefficient = 0.64). In the ADNI cohort, we imputed missing single nucleotide variants.

Conclusion
These results show that our reference alignment and panel can be used to impute missing mtSNVs in existing data obtained from using microarrays, thereby broadening the scope of functional and clinical investigation of mtDNA. This improvement may be particularly useful in studies where participants have been recruited over time and mtDNA data obtained using different methods, enabling better integration of early data collected using less accurate methods with more recent sequence data.
Advance care planning for adolescents with cancer and their parents: study protocol of the BOOST pACP multi-centre randomised controlled trial and process evaluation
Authors: van Driessche Anne , De Vleminck Aline , Gilissen Joni , Kars Marijke C. , van der Werff ten Bosch Jutte , Deliens Luc , Cohen Joachim , Beernaert Kim 
Published: September 2021

Abstract
Background
Research has highlighted the need for evidence-based interventions to improve paediatric advance care planning (pACP) in adolescents with cancer. Although adolescents express the desire and ability to share their values, beliefs and preferences for treatment, there is a lack of structured multicomponent interventions to improve parent-adolescent communication on different ACP themes including those not limited to end-of-life care. The aim of this study is to evaluate the effectiveness and implementation, context and mechanisms of impact of a novel ACP program in paediatric oncology.

Methods
We will conduct a multi-centre parallel-group randomised controlled superiority trial with embedded mixed-methods process evaluation in Flanders, Belgium. Adolescents aged 10–18 who have cancer, and their parent(s) will be recruited via all four university hospitals in Flanders, Belgium, and support groups. Families will be randomised to receive care as usual or the multicomponent BOOST pACP program, consisting of three conversation sessions between an external facilitator and the adolescent and parent(s).
The primary endpoint is improved parent-adolescent communication from the perspective of the adolescent. Secondary endpoints are adolescents’ and parents’ attitudes, self-efficacy, intention and behaviour regarding talking about ACP themes with each other, parents’ perspective of shared decision making in the last clinical encounter, and the paediatric oncologist’s intention and behaviour regarding talking about ACP themes with the family.
Measurements will be performed at baseline, at 3 months and at 7 months using structured self-reported questionnaires. We will perform a process evaluation in the intervention group, with measurement throughout and post-intervention, using structured diaries filled out by the facilitators, interviews with facilitators, interviews with involved paediatric oncology teams, and audio-recordings of the BOOST pACP conversations.

Discussion
The BOOST pACP program has been developed to stimulate conversations on ACP themes between parent(s) and the adolescents, simultaneously lowering the threshold to discuss similar themes with healthcare professionals, initiating a process of normalization and integration of ACP in standard care. This combined outcome and process evaluation aims to contribute to building the necessary evidence to improve ACP in paediatric oncology.

Trial registration
The study is registered at ISRCTN, ISRCTN33228289. Registration date: January 22, 2021.
In vitro inhibitory effect of obtusofolin on the activity of CYP3A4, 2C9, and 2E1
Authors: Liu Na , Chen Ping , Du Xiaojun , Sun Junxia , Han Shasha 
Published: September 2021

Abstract
Background
Obtusofolin is the major active ingredient of Catsia tora L., which possesses the activity of improving eyesight and protecting the optic nerve. Investigation on the interaction of obtusofolin with cytochrome P450 enzymes (CYP450s) could provide a reference for the clinical application of obtusofolin.

Methods
The effect of obtusofolin on the activity of CYP450s was investigated in the presence of 100 μM obtusofolin in pooled human liver microsomes (HLMs) and fitted with the Lineweaver–Burk plots to characterize the specific inhibition model and kinetic parameters.

Results
Obtusofolin was found to significantly inhibited the activity of CYP3A4, 2C9, and 2E1. In the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM obtusofolin, the inhibition of these CYP450s showed a dose-dependent manner with the IC50 values of 17.1 ± 0.25, 10.8 ± 0.13, and 15.5 ± 0.16 μM, respectively. The inhibition of CYP3A4 was best fitted with the non-competitive inhibition model with the Ki value of 8.82 μM. While the inhibition of CYP2C9 and 2E1 was competitive with the Ki values of 5.54 and 7.79 μM, respectively. After incubating for 0, 5, 10, 15, and 30 min, the inhibition of CYP3A4 was revealed to be time-dependent with the KI value of 4.87 μM− 1 and the Kinact value of 0.0515 min− 1.

Conclusions
The in vitro inhibitory effect of obtusofolin implying the potential drug-drug interaction between obtusofolin and corresponding substrates, which needs further in vivo validations.
Predictive factors of diagnostic and therapeutic divergence in a nationwide cohort of patients seeking second medical opinion
Authors: Sanchez Stéphane , Adamowicz Isabelle , Chrusciel Jan , Denormandie Philippe , Denys Pierre , Degos Laurent 
Published: September 2021

Abstract
Objectives
The aim of this study was to describe the profile of patients who sought a second medical opinion (SMO) on their therapeutic or diagnostic strategy using nationwide data from a French physician network dedicated to SMOs.

Methods
An observational cohort study was conducted and the study population consisted of patients residing in France or in the French overseas territories who submitted a request for an SMO through a dedicated platform between January 2016 and October 2020. Patient characteristics were compared between convergent and divergent SMOs. The divergent rate for all patients excluding those with mental diseases were described. Logistic regression was used to estimate the probability of a divergent SMO according to patient characteristics.

Results and discussion
In total, 1,552 adult patients over several French regions were included. The divergence rate was 32.3 % (n = 502 patients). Gynecological [Odds Ratio (OR) and 95 % CI: 5.176 (3.154 to 8.494)], urological [OR 4.246 (2.053 to 8.782)] and respiratory diseases [OR 3.639 (1.357 to 9.758)] had the highest probability of a divergent SMO. Complex cases were also associated with a significantly higher risk of a divergent opinion [OR 2.78 (2.16 to 3.59)]. Age, sex, region and profession were not found to be predictive of a divergent second opinion.

Conclusions
Policymakers should encourage new research on patient outcomes such as mortality and hospitalization rates after a SMO. When proven effective, SMO networks will have the potential to benefit from specific public funding or even play a key role in national healthcare quality improvement programs.
Mitochondrial links between brain aging and Alzheimer’s disease
Authors: Wilkins Heather M. , Swerdlow Russell H. 
Published: September 2021

AbstractAdvancing age is a major risk factor for Alzheimer’s disease (AD). This raises the question of whether AD biology mechanistically diverges from aging biology or alternatively represents exaggerated aging. Correlative and modeling studies can inform this question, but without a firm grasp of what drives aging and AD it is difficult to definitively resolve this quandary. This review speculates over the relevance of a particular hallmark of aging, mitochondrial function, to AD, and further provides background information that is pertinent to and provides perspective on this speculation.
Human gut-derived B. longum subsp. longum strains protect against aging in a d-galactose-induced aging mouse model
Authors: Xiao Yue , Yang Chao , Yu Leilei , Tian Fengwei , Wu Yarong , Zhao Jianxin , Zhang Hao , Yang Ruifu , Chen Wei , Hill Colin , Cui Yujun , Zhai Qixiao 
Published: September 2021

AbstractBackgroundProbiotics have been used to regulate the gut microbiota and physiology in various contexts, but their precise mechanisms of action remain unclear.ResultsBy population genomic analysis of 418Bifidobacterium longumstrains, including 143 newly sequenced in this study, three geographically distinct gene pools/populations, BLAsia1, BLAsia2, and BLothers, were identified. Genes involved in cell wall biosynthesis, particularly peptidoglycan biosynthesis, varied considerably among the core genomes of the different populations, but accessory genes that contributed to the carbohydrate metabolism were significantly distinct. Although active transmission was observed inter-host, inter-country, inter-city, intra-community, and intra-family, a singleB. longumclone seemed to reside within each individual. A significant negative association was observed between host age and relative abundance ofB. longum, while there was a strong positive association between host age and strain genotype [e.g., single nucleotide polymorphisms in the arginine biosynthesis pathway]. Further animal experiments performed with theB. longumisolates via using ad-galactose-induced aging mouse model supported these associations, in whichB. longumstrains with different genotypes in arginine biosynthesis pathway showed divergent abilities on protecting against host aging possibly via their different abilities to modify the metabolism of gut microbes.ConclusionsThis is the first known example of research on the evolutionary history and transmission of this probiotic species. Our results propose a new mechanistic insight for promoting host longevity via the informed use of specific probiotics or molecules.
Critical peak rebate strategy and application to demand response
Authors: Yang Hejun , Zhang Xinyu , Ma Yinghao , Zhang Dabo 
Published: September 2021

AbstractTime-of-use (TOU) pricing strategy is an important component of demand-side management (DSM), but the cost of supplying power during critical peak periods remains high under TOU prices. This affects power system reliability. In addition, TOU prices are usually applicable to medium- and long-term load control but cannot effectively regulate short-term loads. Therefore, this paper proposes an optimization method for TOU pricing and changes the electricity consumption patterns during the critical peak periods through a critical peak rebate (CPR). This reduces generation costs and improves power system reliability. An optimization model for peak-flat-valley (PFV) period partition is established based on fuzzy clustering and an enumeration iterative technique. A TOU pricing optimization model including grid-side and customer-side benefits is then proposed, and a simulated annealing particle swarm optimization (SAPSO) algorithm is used to solve the problem. Finally, a CPR decision model is developed to further reduce critical peak loads. The effectiveness of the proposed model and algorithm is illustrated through different case studies of the Roy Billinton Test System (RBTS).
Decreased vitamin D levels in children with primary mono-symptomatic nocturnal enuresis
Authors: El-Baz Farida M. , Abdelsayed Marian G. R. , Abdel-Hafeez Aziza S. , Abdelmageed Reham I. 
Published: September 2021

Abstract
Background
Nocturnal enuresis (NE) is a common voiding problem in pediatric populations. Relatively, few studies have investigated the 25-Hydroxyvitamin D and NE associations in children, which may open up a new research area on the effect of vitamin D as nutritional therapy in the treatment of NE. The aim of this study was to determine the level of 25-hydroxyl vitamin D among children and adolescents with nocturnal enuresis in comparison to non-enuretic Egyptian children.

Results
Fifty children (24 females, 26 males) who presented with primary mono-symptomatic nocturnal enuresis (PMNE) and 50 healthy children (23 females, 27 males) were recruited in this study. A structured questionnaire focusing on demographic, socioeconomic, and frequency of bed-wetting were collected, and vitamin D serum levels were assessed in all children. In the NE group, the mean value of serum vitamin D levels was lower than the control (19.0 ± 6.5 versus 23.89 ± 4.19; P < 0.0001). Serum 25-hydroxyvitamin D levels were abnormal (< 20 ng/mL) in 46% of children with NE and 16% of controls (P < 0.001). The higher bed-wetting frequencies were associated with lower levels of 25(OH) D (Every night: 7.0 ± 1.4, 3–5 time/week: 11.2 ± 1.7, 1–3 times/week: 17.6 ± 3.7, < 2times/week: 22.4 ± 2.9, Once/6 month: 24.1 ± 4.3 (ng/ml), P < 0.001).

Conclusion
A difference in serum 25-hydroxyvitamin D levels was found between the two study groups. There is a need for more studies to explain vitamin D deficiency in larger series so that this test can be used in regular enuretic child investigations.
Assessment of serum vitamin D levels in Egyptian children with beta-thalassemia major
Authors: Abdelmotaleb Ghada Saad , Behairy Ola Galal , El Azim Khalid Eid Abd , El-Hassib Dalia Mohamed Abd , Hemeda Tasbeh Mohamed 
Published: September 2021

Abstract
Background
Beta-thalassemia major patients are at increased risk of complications including endocrinopathies and bone disease due to iron overload. So, this study aimed to assess the growth parameters, serum levels of 25-OH-vitamin D, calcium, and phosphorous in children with beta-thalassemia major. This was a case-control study that included 55 children with beta-thalassemia major compared with 30 sex- and age-matched healthy children that served as a control group. All enrolled children were subjected to full history taking, clinical examination including anthropometric measurements, and laboratory investigations including complete blood count, serum ferritin, levels of serum calcium, phosphorus, and 25-OH-vitamin D.

Results
Body mass index was statistically significantly lower in the thalassemic group (P < 0.001). It was observed that vitamin D levels were significantly lower in thalassemic patients than in controls (P value < .0001). The mean serum 25-OH-vitamin D levels were 19.84 ± 5.79 ng/ml and 44.98 ± 5.77 ng/ml, respectively; 22 cases (40%) had insufficient vitamin D, and 5 cases (9%) had deficient vitamin D. Regarding serum calcium and phosphorous, there was no significant difference between the thalassemic and control groups.

Conclusion
Children with beta-thalassemia major had low body mass index and metabolic abnormality in the form of lower serum levels of vitamin D that signify the importance of therapeutic interventions.
Pseudotail with closed neural tube defect and neurogenic bladder masquerading as posterior urethral valve: a case report
Authors: Singh Ram Jeewan , Ali Md Mokarram , Kumar Amit , Rashi Rashi , Sinha Amit Kumar , Kumar Bindey 
Published: September 2021

Abstract
Background
Pseudotail with occult spinal dysraphism with neurological deficit is a rare phenomenon. Ignoring pseudotail as sign of occult spinal dysraphism may lead to catastrophe in diagnosis and further management.

Case presentation
We are reporting a case of a 30-month-old male child who presented with a tail-like structure at lower back and dribbling of urine since birth. On initial evaluation at some other hospital, he was misdiagnosed as posterior urethral valve and underwent fulguration of valve. However, dribbling of urine persisted after initial procedure. On evaluation at our center, he was found to have pseudotail with occult spinal dysraphism and neurogenic bladder.

Conclusion
Pseudotail with occult spinal dysraphism with neurological deficit is a rare phenomenon. Neurogenic bladder in such case can be misdiagnosed as posterior urethral valve. So, neurogenic bladder with pseudotail should be evaluated cautiously to avoid misdiagnosis and mismanagement.
The Transcriptome and Epigenome Reveal Novel Changes in Transcription Regulation During Pancreatic Rat Islet Maturation
Authors: Lien Yu-Chin , Lu Xueqing Maggie , Won Kyoung-Jae , Wang Paul Zhiping , Osei-Bonsu Wendy , Simmons Rebecca A 
Published: September 2021

AbstractIslet function is critical for normal glucose homeostasis. Unlike adult β cells, fetal and neonatal islets are more proliferative and have decreased insulin secretion in response to stimuli. However, the underlying mechanisms governing functional maturity of islets have not been completely elucidated. Pancreatic islets comprise different cell types. The microenvironment of islets and interactions between these cell types are critical for β-cell development and maturation. Thus, the study of intact islets is optimal to identify novel molecular mechanisms controlling islet functional development. Transcriptomes and genome-wide histone landscapes of H3K4me3, H3K27me3, and H3K27Ac from intact islets isolated from 2- and 10-week-old Sprague-Dawley rats were integrated to elucidate genes and pathways modulating islet development, as well as the contribution of epigenetic regulation. A total of 4489 differentially expressed genes were identified; 2289 and 2200 of them were up- and down-regulated in 10-week islets, respectively. Ingenuity Pathway Analysis revealed critical pathways regulating functional maturation of islets, including nutrient sensing, neuronal function, immune function, cell replication, and extracellular matrix. Furthermore, we identified significant changes in enrichment of H3K4me3, H3K27me3, and H3K27Ac marks, which correlated with expression changes of genes critical for islet function. These histone marks were enriched at critical transcription factor-binding motifs, such as Hoxa9, C/EBP-β, Gata1, Foxo1, E2f1, E2f3, and Mafb. In addition, our chromatin immunoprecipitation sequencing data revealed multiple potential bivalent genes whose poised states changed with maturation. Collectively, our current study identified critical novel pathways for mature islet function and suggested a role for histone modifications in regulating islet development and maturation.
Neurodegenerative Disease: Roles for Sex, Hormones, and Oxidative Stress
Authors: Sumien Nathalie , Cunningham J Thomas , Davis Delaney L , Engelland Rachel , Fadeyibi Oluwadarasimi , Farmer George E , Mabry Steve , Mensah-Kane Paapa , Trinh Oanh T P , Vann Philip H , Wilson E Nicole , Cunningham Rebecca L 
Published: September 2021

Abstract
Neurodegenerative diseases cause severe impairments in cognitive and motor function. With an increasing aging population and the onset of these diseases between 50 and 70 years, the consequences are bound to be devastating. While age and longevity are the main risk factors for neurodegenerative diseases, sex is also an important risk factor. The characteristic of sex is multifaceted, encompassing sex chromosome complement, sex hormones (estrogens and androgens), and sex hormone receptors. Sex hormone receptors can induce various signaling cascades, ranging from genomic transcription to intracellular signaling pathways that are dependent on the health of the cell. Oxidative stress, associated with aging, can impact the health of the cell. Sex hormones can be neuroprotective under low oxidative stress conditions but not in high oxidative stress conditions. An understudied sex hormone receptor that can induce activation of oxidative stress signaling is the membrane androgen receptor (mAR). mAR can mediate nicotinamide adenine dinucleotide-phosphate (NADPH) oxidase (NOX)-generated oxidative stress that is associated with several neurodegenerative diseases, such as Alzheimer disease. Further complicating this is that aging can alter sex hormone signaling. Prior to menopause, women experience more estrogens than androgens. During menopause, this sex hormone profile switches in women due to the dramatic ovarian loss of 17β-estradiol with maintained ovarian androgen (testosterone, androstenedione) production. Indeed, aging men have higher estrogens than aging women due to aromatization of androgens to estrogens. Therefore, higher activation of mAR-NOX signaling could occur in menopausal women compared with aged men, mediating the observed sex differences. Understanding of these signaling cascades could provide therapeutic targets for neurodegenerative diseases.