bluuebunny/crossref_metadata_2025_split huggingface dataset:
No causal effects of plasma homocysteine levels on the risk of coronary heart disease or acute myocardial infarction: A Mendelian randomization study
Authors: Miao Liu , Deng Guo-Xiong , Yin Rui-Xing , Nie Rong-Jun , Yang Shuo , Wang Yong , Li Hui 
Published: December 2019

Abstract

Background
Although many observational studies have shown an association between plasma homocysteine levels and cardiovascular diseases, controversy remains. In this study, we estimated the role of increased plasma homocysteine levels on the etiology of coronary heart disease and acute myocardial infarction.

Methods
A two-sample Mendelian randomization study on disease was conducted, i.e. “coronary heart disease” (n = 184,305) and “acute myocardial infarction” (n = 181,875). Nine single nucleotide polymorphisms, which were genome-wide significantly associated with plasma homocysteine levels in 57,644 subjects from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium genome-wide association study and were known to be associated at p &lt; 5×10–8, were used as an instrumental variable.

Results
None of the nine single nucleotide polymorphisms were associated with coronary heart disease or acute myocardial infarction (p &gt; 0.05 for all). Mendelian randomization analysis revealed no causal effects of plasma homocysteine levels, either on coronary heart disease (inverse variance weighted; odds ratio = 1.015, 95% confidence interval = 0.923–1.106, p = 0.752) or on acute myocardial infarction (inverse variance weighted; odds ratio = 1.037, 95% confidence interval = 0.932–1.142, p = 0.499). The results were consistent in sensitivity analyses using the weighted median and Mendelian randomization-Egger methods, and no directional pleiotropy (p = 0.213 for coronary heart disease and p = 0.343 for acute myocardial infarction) was observed. Sensitivity analyses confirmed that plasma homocysteine levels were not significantly associated with coronary heart disease or acute myocardial infarction.

Conclusions
The findings from this Mendelian randomization study indicate no causal relationship between plasma homocysteine levels and coronary heart disease or acute myocardial infarction. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.
miR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation
Authors: Moimas Silvia , Salton Francesco , Kosmider Beata , Ring Nadja , Volpe Maria C. , Bahmed Karim , Braga Luca , Rehman Michael , Vodret Simone , Graziani Maria Laura , Wolfson Marla R. , Marchetti Nathaniel , Rogers Thomas J. , Giacca Mauro , Criner Gerard J. , Zacchigna Serena , Confalonieri Marco 
Published: December 2019

RationaleAlveolar type II (ATII) cells act as adult stem cells contributing to alveolar type I (ATI) cell renewal and play a major role in idiopathic pulmonary fibrosis (IPF), as supported by familial cases harbouring mutations in genes specifically expressed by these cells. During IPF, ATII cells lose their regenerative potential and aberrantly express pathways contributing to epithelial–mesenchymal transition (EMT). The microRNA miR-200 family is downregulated in IPF, but its effect on human IPF ATII cells remains unproven. We wanted to 1) evaluate the characteristics and transdifferentiating ability of IPF ATII cells, and 2) test whether miR-200 family members can rescue the regenerative potential of fibrotic ATII cells.MethodsATII cells were isolated from control or IPF lungs and cultured in conditions promoting their transdifferentiation into ATI cells. Cells were either phenotypically monitored over time or transfected with miR-200 family members to evaluate the microRNA effect on the expression of transdifferentiation, senescence and EMT markers.ResultsIPF ATII cells show a senescent phenotype (p16 and p21), overexpression of EMT (ZEB1/2) and impaired expression of ATI cell markers (AQP5 and HOPX) after 6 days of culture in differentiating medium. Transfection with certain miR-200 family members (particularly miR-200b-3p and miR-200c-3p) reduced senescence marker expression and restored the ability to transdifferentiate into ATI cells.ConclusionsWe demonstrated that ATII cells from IPF patients express senescence and EMT markers, and display a reduced ability to transdifferentiate into ATI cells. Transfection with certain miR-200 family members rescues this phenotype, reducing senescence and restoring transdifferentiation marker expression.
Primary headache disorders among the adult population of Mongolia: prevalences and associations from a population-based survey
Authors: Luvsannorov Otgonbayar , Tsenddorj Byambasuren , Baldorj Dorjkhand , Enkhtuya Selenge , Purev Delgermaa , Thomas Hallie , Steiner Timothy J. 
Published: December 2019

Abstract
Background
In the ongoing Global Campaign endeavour to improve knowledge and awareness of headache prevalence worldwide, Mongolia is a country of interest. It sits between Russia and China, in which prevalence is, respectively, much higher and much lower than the estimated global mean. We conducted a population-based study in Mongolia both to add to knowledge and to inform local health policy.

Methods
Using standardized methodology with cluster random sampling, we selected Mongolian adults (aged 18–65 years) from five regions reflecting the country’s diversities. They were interviewed by trained researchers, cold-calling at their homes, using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire following pilot-testing. ICHD-3 beta diagnostic criteria were applied.

Results
N = 2043 (mean age 38.0 [±13.4] years, 40% urban-dwelling and 60% rural), with a non-participation proportion of 1.7%. Males were somewhat underrepresented, for which corrections were made. The crude 1-year prevalence of any headache was 66.1% (95% CI: 64.0–68.2%), with a strong female preponderance (OR: 2.2; p < 0.0001). Age- and gender-adjusted prevalences were: migraine 23.1% (for females, OR = 2.2; p < 0.0001); tension-type headache (TTH) 29.1% (no gender difference); probable medication-overuse headache (pMOH) 5.7% (trending towards higher in females); other headache on ≥15 days/month 5.0% (for females, OR = 2.2; p = 0.0008). Unclassified cases were only 35 (1.7%). Any headache yesterday was reported by 410 (20.1%; for females, OR = 2.4; p < 0.0001). Only pMOH showed a strong association with age, peaking in middle years with a 5-fold increase in prevalence. Migraine showed a consistent association with educational level, while pMOH showed the reverse, and was also more common among other groups than among participants who were single (never married). Migraine was less common among rural participants than urban (OR: 0.80; p = 0.0326), while pMOH again showed the reverse (OR: 2.4; p < 0.0001). Finally, pMOH (but not migraine or TTH) was significantly associated with obesity (OR: 1.8; p = 0.0214).

Conclusion
Headache disorders are common in Mongolia, with, most notably, a very high prevalence of headache on ≥15 days/month corroborated by the high prevalence of headache yesterday. The picture is very like that in Russia, and dissimilar to China. There are messages for national health policy.
The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex
Authors: Wong Michael 
Published: December 2019

AbstractBackgroundTuberous sclerosis complex (TSC) is a genetic disorder characterized by severe neurological manifestations, including epilepsy, intellectual disability, autism, and a range of other behavioral and psychiatric symptoms, collectively referred to as TSC-associated neuropsychiatric disorders (TAND). Various tumors and hamartomas affecting different organs are the pathological hallmarks of the disease, especially cortical tubers of the brain, but specific cellular and molecular abnormalities, such as involving the mechanistic target of rapamycin (mTOR) pathway, have been identified that also cause or contribute to neurological manifestations of TSC independent of gross structural lesions. In particular, while neurons are immediate mediators of neurological symptoms, different types of glial cells have been increasingly recognized to play important roles in the phenotypes of TSC.Main bodyThis review summarizes the literature supporting glial dysfunction from both mouse models and clinical studies of TSC. In particular, evidence for the role of astrocytes, microglia, and oligodendrocytes in the pathophysiology of epilepsy and TAND in TSC is analyzed. Therapeutic implications of targeting glia cells in developing novel treatments for the neurological manifestations of TSC are also considered.ConclusionsDifferent types of glial cells have both cell autonomous effects and interactions with neurons and other cells that are involved in the pathophysiology of the neurological phenotype of TSC. Targeting glial-mediated mechanisms may represent a novel therapeutic approach for epilepsy and TAND in TSC patients.
Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder
Authors:   on behalf of the TACERN Study Group, Prohl Anna K. , Scherrer Benoit , Tomas-Fernandez Xavier , Davis Peter E. , Filip-Dhima Rajna , Prabhu Sanjay P. , Peters Jurriaan M. , Bebin E. Martina , Krueger Darcy A. , Northrup Hope , Wu Joyce Y. , Sahin Mustafa , Warfield Simon K. 
Published: December 2019

AbstractBackgroundAutism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants.MethodsTSC infants were recruited within their first year of life and longitudinally imaged at time of recruitment, 12 months of age, and at 24 months of age. Autism was diagnosed at 24 months of age with the ADOS-2. There were 108 subjects (62 TSC-ASD, 55% male; 46 TSC+ASD, 52% male) with at least one MRI and a 24-month ADOS, for a total of 187 MRI scans analyzed (109 TSC-ASD; 78 TSC+ASD). Diffusion tensor imaging properties of multiple white matter fiber bundles were sampled using a region of interest approach. Linear mixed effects modeling was performed to test the hypothesis that infants who develop ASD exhibit poor white matter microstructural integrity over the first 2 years of life compared to those who do not develop ASD.ResultsSubjects with TSC and ASD exhibited reduced fractional anisotropy in 9 of 17 white matter regions, sampled from the arcuate fasciculus, cingulum, corpus callosum, anterior limbs of the internal capsule, and the sagittal stratum, over the first 2 years of life compared to TSC subjects without ASD. Mean diffusivity trajectories did not differ between groups.ConclusionsUnderconnectivity across multiple white matter fiber bundles develops over the first 2 years of life in subjects with TSC and ASD. Future studies examining brain-behavior relationships are needed to determine how variation in the brain structure is associated with ASD symptoms.
The impact of expressive language development and the left inferior longitudinal fasciculus on listening and reading comprehension
Authors: Del Tufo Stephanie N. , Earle F. Sayako , Cutting Laurie E. 
Published: December 2019

AbstractBackgroundDuring the first 3-years of life, as the brain undergoes dramatic growth, children begin to develop speech and language. Hallmarks of this progression are seen when children reach developmental milestones, forming the foundation of language. Expressive language milestones, such as the production of a child’s first word, are delayed in 5–8% of children. While for some children delays in reaching these milestones are harbingers of developmental disorders, for others expressive language delays appear to resolve. Regardless of whether or not early language skills appear resolved, difficulty with later comprehension is a likely outcome. Whether this heightened risk for poor comprehension differs based on text features, individual characteristics, or receipt of intervention remains unknown. Moreover, this relationship between expressive language development and comprehension is not yet linked to neurobiology, though the inferior longitudinal fasciculus (ILF) is a potential neurobiological correlate. Therefore, we investigated the impact of, and interactions between, expressive language development, early intervention, and the ILF on comprehension.MethodsLongitudinal recurrent survival analyses predicted the risk of answering a comprehension question incorrectly. Predictors of comprehension included expressive language development, passage features, participant characteristics, fractional anisotropy, receipt of early intervention, and later diagnosis of speech or language disorders.ResultsChildren with later expressive language milestones had poorer comprehension. When comprehension text features were examined, children with later milestones had poorer listening and reading comprehension, and poorer narrative and expository comprehension. The left ILF acted as a neurodevelopmental correlate, one that moderated the relationship between expressive language milestones and comprehension. Specifically, the left ILF exacerbated the relationship for those who did not receive early intervention and buffered the relationship for those who received intervention services. Early intervention decreased the risk of poor comprehension by 39% for children later diagnosed with a speech or language disorder.ConclusionsEarly intervention should be provided for children with delayed expressive language milestones, particularly those who are at risk for speech or language disorders. The ILF plays a critical role in the relationship between expressive language development and comprehension, which may be that of a protective factor for children with the most severe early issues with speech and language.
Reducing Th2 inflammation through neutralizing IL-4 antibody rescues myelination in IUGR rat brain
Authors: Zanno Allison E. , Romer Micah A. , Fox Lauren , Golden Thea , Jaeckle-Santos Lane , Simmons Rebecca A. , Grinspan Judith B. 
Published: December 2019

Abstract
Background
Intrauterine growth restriction (IUGR) is a common complication of pregnancy and is associated with significant neurological deficits in infants, including white matter damage. Previous work using an animal model of IUGR has demonstrated that IUGR rats exhibit neurobehavioral deficits and developmental delays in oligodendrocyte maturation and myelination, but the mechanisms which cause this delay are unknown. Inflammation may be an important etiological factor in IUGR and has been recognized as playing a fundamental role in the pathogenesis of myelin disorders, including cerebral palsy.

Methods
To create the model, the uterine arteries of pregnant rats were ligated at embryonic day 15. Rats delivered spontaneously. Cytokine and chemokine expression was evaluated at one prenatal and three postnatal time points, and myelin protein expression and oligodendrocyte cell numbers were evaluated by several methods at postnatal day 14. IL-4 was identified as a potential inhibitor of myelination, and rat pups were injected with IL-4 function blocking antibody from postnatal days 1–5 and myelination was assessed.

Results
Here, we show a novel mechanism of white matter injury. IUGR induces an exaggerated Th2 response in the developing rat brain, including upregulation of several Th2 cytokines. Of these, IL-4 is significantly increased during the period corresponding to robust developmental myelination. We show that neutralizing IL-4 antibody therapy given in the newborn period ameliorates inflammation and restores myelin protein expression and oligodendrocyte cell number in the IUGR brain to control levels, demonstrating a novel role for Th2 responses and IL-4 in IUGR and white matter injury. In addition, IL-4 directly affects oligodendrocytes in vitro decreasing differentiation.

Conclusions
In this study, we have identified inflammation as a factor in the decrease in myelin seen in an animal model of IUGR. IL-4, an inflammatory protein often thought to be protective in the adult, is specifically increased, and treatment of these animals to prevent this increase ameliorates white matter damage. Our results suggest that the immune system plays a role in IUGR that is different in the perinatal period than in the adult and preventing this exaggerated Th2 response may be a potential therapeutic target.
Adaptation of the Clinical Dementia Rating Scale for adults with Down syndrome
Authors: Lessov-Schlaggar Christina N. , del Rosario Olga L. , Morris John C. , Ances Beau M. , Schlaggar Bradley L. , Constantino John N. 
Published: December 2019

AbstractBackgroundAdults with Down syndrome (DS) are at increased risk for Alzheimer disease dementia, and there is a pressing need for the development of assessment instruments that differentiate chronic cognitive impairment, acute neuropsychiatric symptomatology, and dementia in this population of patients.MethodsWe adapted a widely used instrument, the Clinical Dementia Rating (CDR) Scale, which is a component of the Uniform Data Set used by all federally funded Alzheimer Disease Centers for use in adults with DS, and tested the instrument among 34 DS patients recruited from the community. The participants were assessed using two versions of the modified CDR—a caregiver questionnaire and an in-person interview involving both the caregiver and the DS adult. Assessment also included the Dementia Scale for Down Syndrome (DSDS) and the Raven’s Progressive Matrices to estimate IQ.ResultsBoth modified questionnaire and interview instruments captured a range of cognitive impairments, a majority of which were found to be chronic when accounting for premorbid function. Two individuals in the sample were strongly suspected to have early dementia, both of whom had elevated scores on the modified CDR instruments. Among individuals rated as having no dementia based on the DSDS, about half showed subthreshold impairments on the modified CDR instruments; there was substantial agreement between caregiver questionnaire screening and in-person interview of caregivers and DS adults.ConclusionsThe modified questionnaire and interview instruments capture a range of impairment in DS adults, including subthreshold symptomatology, and the instruments provide complementary information relevant to the ascertainment of dementia in DS. Decline was seen across all cognitive domains and was generally positively related to age and negatively related to IQ. Most importantly, adjusting instrument scores for chronic, premorbid impairment drastically shifted the distribution toward lower (no impairment) scores.
The Rice G Protein γ Subunit DEP1/qPE9–1 Positively Regulates Grain-Filling Process by Increasing Auxin and Cytokinin Content in Rice Grains
Authors: Zhang Dongping , Zhang Minyan , Zhou Yong , Wang Yuzhu , Shen Jinyu , Chen Hongyingxue , Zhang Lin , Lü Bing , Liang Guohua , Liang Jiansheng 
Published: December 2019

AbstractHeterotrimeric G protein-mediated signal transduction is one of the most important and highly conserved signaling pathways in eukaryotes, which involves in the regulation of many important biological processes. As compared with those in mammals and Arabidopsis thaliana, the functions of rice heterotrimeric G protein and their molecular mechanisms are largely unknown. The rice genome contains a single Gα (RGA1) and Gβ (RGB1), and five Gγ (RGG1, RGG2, GS3, DEP1/qPE9–1, and GGC2) subunits. Recent genetic studies have shown that DEP1/qPE9–1, an atypical putative Gγ protein, is responsible for the grain size as well as the dense and erect panicles, but the biochemical and molecular mechanisms underlying the control of grain size are not well understood. Here, we report that rice plants carrying DEP1/qPE9–1 have more endosperm cells per grain than plants contain the dep1/qpe9–1 allele. The DEP1/qPE9–1 line has a higher rate and more prolonged period of starch accumulation than the dep1/qpe9–1 line. Additionally, the expression of several essential genes encoding enzymes catalyzing sucrose metabolism and starch biosynthesis is higher in the DEP1/qPE9–1 line than in the dep1/qpe9–1 line, especially from the mid to late grain-filling stage. Grains of the DEP1/qPE9–1 line also have higher contents of three phytohormones, ABA, auxin and cytokinin. Exogenous application of auxin or cytokinin enhanced the starch accumulation and the expression of genes encoding grain-filling-related enzymes in the grains of dep1/qpe9–1, whereas ABA produced no effects. Based on these results, we conclude that DEP1/qPE9–1 positively regulates starch accumulation primarily through auxin and cytokinin, which enhance the expression of genes encoding starch biosynthesis during the mid to late grain-filling stage, resulting in increased duration of the grain-filling process.
Comparison of prostate size and anthropometric parameters between diabetic and non-diabetic Congolese patients who underwent transurethral prostate resection in the Democratic Republic of Congo
Authors: Mubenga L. E. , Chimanuka D. , De Groote P. , Bwenge E. , Hermans M. P. , Tombal B. 
Published: December 2019

AbstractBackgroundBenign prostate hyperplasia (BPH) and type 2 diabetes mellitus are prevalent in older men, and both represent a challenge to public health. Prior studies reported a correlation between BPH and (hyper)glycaemia, a component of the metabolic syndrome, which is on the increase in sub-Saharan Africa (SSA) due to rapid modernization. This study was designed to evaluate the association of prostate volume and anthropometric parameters among diabetic and non-diabetic patients who had transurethral resection of the prostate (TURP) for BPH.ResultsWe analyzed data of 159 selected patients who had TURP over a three-year period (February 2014–January 2017) for histologically confirmed BPH. Mean age in the entire cohort was 68 ± 8.5 years. Out of the 159 patients, 94 (59.1%) were non-diabetics and 65 (40.9%) were diabetics. International Prostate Symptom Score (IPSS) and fasting blood glucose were significantly higher in diabetic than in non-diabetic group (28.6 ± 4.3 vs 25.6 ± 6.4, andp0.005; 121.7 ± 45.7 vs 85.4 ± 11.7 mg/dl, andp < 0.001, respectively). BMI and waist circumference were statistically greater in non-diabetics than in diabetics (25.1 ± 3.3 kg/m2vs 23.6 ± 3.5 kg/m2, andp0.008; 94.6 cm ± 10.3 vs 90.6 ± 10.4 cm, andp0.018). Diabetic patients had larger prostate volume than non-diabetic in the working age subgroup only (< 65 years of age); beyond 65 years, this difference was not consistent (62.6 ± 23.1 cc vs 50.1 ± 20.7 cc, andp0.027; 56.2 ± 23.7 cc vs 49 ± 20.2 cc, andp0.15, respectively). Prostate size was significantly associated with fasting blood glucose (p = 0.002) and PSA (p = 0.027). However, prostate size was not related to age, presence of diabetes, BMI, waist circumference, IPSS, quality of life score, and duration of symptoms.ConclusionProstate volume is not correlated with anthropometric parameters in diabetic and non-diabetic Congolese patients who had TURP in South Kivu. Diabetics were not obese and yet had larger prostate volume than non-diabetics < 65 years of age. It is hoped that these results would form groundwork for further studies on this topic in SSA region.