bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease
Authors: Keret Ophir , Staffaroni Adam M. , Ringman John M. , Cobigo Yann , Goh Sheng‐Yang M. , Wolf Amy , Allen Isabel Elaine , Salloway Stephen , Chhatwal Jasmeer , Brickman Adam M. , Reyes‐Dumeyer Dolly , Bateman Randal J. , Benzinger Tammie L.S. , Morris John C. , Ances Beau M. , Joseph‐Mathurin Nelly , Perrin Richard J. , Gordon Brian A. , Levin Johannes , Vöglein Jonathan , Jucker Mathias , la Fougère Christian , Martins Ralph N. , Sohrabi Hamid R. , Taddei Kevin , Villemagne Victor L. , Schofield Peter R. , Brooks William S. , Fulham Michael , Masters Colin L. , Ghetti Bernardino , Saykin Andrew J. , Jack Clifford R. , Graff‐Radford Neill R. , Weiner Michael , Cash David M. , Allegri Ricardo F. , Chrem Patricio , Yi Su , Miller Bruce L. , Rabinovici Gil D. , Rosen Howard J. ,   Dominantly Inherited Alzheimer Network
Published: July 2021

AbstractIntroductionAsymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD‐MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD‐MC and could help predict risk for dementia during trial enrollment.MethodsWe created a dementia risk score by entering standardized gray‐matter volumes from 231 DIAD‐MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD‐MC followed longitudinally.ResultsOur risk score separated asymptomatic versus demented DIAD‐MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%–98.2%]) and improved prediction beyond established methods based on familial age of onset.DiscussionIndividualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD‐MC participants for prevention trials.
Brain correlates of urban environmental exposures in cognitively unimpaired individuals at increased risk for Alzheimer's disease: A study on Barcelona's population
Authors: Falcón Carles , Gascon Mireia , Molinuevo José Luis , Operto Grégory , Cirach Marta , Gotsens Xavier , Fauria Karine , Arenaza‐Urquijo Eider M. , Pujol Jesús , Sunyer Jordi , Nieuwenhuijsen Mark J. , Gispert Juan Domingo , Crous‐Bou Marta ,   for the ALFA Study
Published: July 2021

AbstractIntroductionUrban environmental exposures might contribute to the incidence of Alzheimer's disease (AD). Our aim was to identify structural brain imaging correlates of urban environmental exposures in cognitively unimpaired individuals at increased risk of AD.MethodsTwo hundred twelve participants with brain scans and residing in Barcelona, Spain, were included. Land use regression models were used to estimate residential exposure to air pollutants. The daily average noise level was obtained from noise maps. Residential green exposure indicators were also generated. A cerebral 3D‐T1 was acquired to obtain information on brain morphology. Voxel‐based morphometry statistical analyses were conducted to determine the areas of the brain in which regional gray matter (GM) and white matter (WM) volumes were associated with environmental exposures.ResultsExposure to nitrogen dioxide was associated with lower GM volume in the precuneus and greater WM volume in the splenium of the corpus callosum and inferior longitudinal fasciculus. In contrast, exposure to fine particulate matter was associated with greater GM in cerebellum and WM in the splenium of corpus callosum, the superior longitudinal fasciculus, and cingulum cingulate gyrus. Noise was positively associated with WM volume in the body of the corpus callosum. Exposure to greenness was associated with greater GM volume in the middle frontal, precentral, and the temporal pole.DiscussionIn cognitively unimpaired adults with increased risk of AD, exposure to air pollution, noise, and green areas are associated with GM and WM volumes of specific brain areas known to be affected in AD, thus potentially conferring a higher vulnerability to the disease.
Characteristics and metabolic patterns of soil methanogenic archaea communities in the high‐latitude natural forested wetlands of China
Authors: Wu Di , Zhao Caihong , Bai Hui , Feng Fujuan , Sui Xin , Sun Guangyu 
Published: July 2021

AbstractSoil methanogenic microorganisms are one of the primary methane‐producing microbes in wetlands. However, we still poorly understand the community characteristic and metabolic patterns of these microorganisms according to vegetation type and seasonal changes. Therefore, to better elucidate the effects of the vegetation type and seasonal factors on the methanogenic community structure and metabolic patterns, we detected the characteristics of the soil methanogenic mcrA gene from three types of natural wetlands in different seasons in the Xiaoxing'an Mountain region, China. The results indicated that the distribution of Methanobacteriaceae (hydrogenotrophic methanogens) was higher in winter, while Methanosarcinaceae and Methanosaetaceae accounted for a higher proportion in summer. Hydrogenotrophic methanogenesis was the dominant trophic pattern in each wetland. The results of principal coordinate analysis and cluster analysis showed that the vegetation type considerably influenced the methanogenic community composition. The methanogenic community structure in the Betula platyphylla–Larix gmelinii wetland was relatively different from the structure of the other two wetland types. Indicator species analysis further demonstrated that the corresponding species of indicator operational taxonomic units from the Alnus sibirica wetland and the Betula ovalifolia wetland were similar. Network analysis showed that cooperative and competitive relationships exist both within and between the same or different trophic methanogens. The core methanogens with higher abundance in each wetland were conducive to the adaptation to environmental disturbances. This information is crucial for the assessment of metabolic patterns of soil methanogenic archaea and future fluxes in the wetlands of the Xiaoxing'an Mountain region given their vulnerability.
Differential effects of estradiol and progesterone on human T cell activation in vitro
Authors: Papapavlou Georgia , Hellberg Sandra , Raffetseder Johanna , Brynhildsen Jan , Gustafsson Mika , Jenmalm Maria C. , Ernerudh Jan 
Published: July 2021

AbstractEstradiol (E2) and progesterone (P4) are steroid hormones important for the regulation of immune responses during pregnancy. Their increasing levels coincide with an improvement of T cell‐mediated diseases such as multiple sclerosis (MS). Although immune‐endocrine interactions are involved in this phenomenon, the relative contribution of hormones is not known. We here report a direct comparison of E2‐ and P4‐mediated effects on human CD4+ T cells, key cells in immune regulation. T cells were stimulated to obtain different activation levels and exposed to a broad range of hormone concentrations. Activation level was assessed by CD69/CD25 expression by flow cytometry, and secreted proteins (n = 196) were measured in culture supernatants using proximity extension assay and electrochemiluminescence immunoassay. We found that in low activated cells, pregnancy‐relevant E2 concentrations increased activation and the secretion of several immune‐ and inflammation‐related proteins. P4, on the other hand, showed a biphasic pattern, where serum‐related concentrations upregulated activation and protein secretion while placenta‐relevant concentrations induced a prominent dampening irrespective of the initial activation level. Our results demonstrate the importance of P4 as a major hormone in the immune modulation of T cells during pregnancy and emphasize the need to further evaluate its potency in the treatment of diseases like MS.
Abortive HIV‐1 RNA induces pro‐IL‐1β maturation via protein kinase PKR and inflammasome activation in humans
Authors: Stunnenberg Melissa , van Hamme John L. , Trimp Marjolein , Gringhuis Sonja I. , Geijtenbeek Teunis B.H. 
Published: July 2021

AbstractThe proinflammatory cytokine IL‐1β mediates high levels of immune activation observed during acute and chronic human immunodeficiency virus 1 (HIV‐1) infection. Little is known about the mechanisms that drive IL‐1β activation during HIV‐1 infection. Here, we have identified a crucial role for abortive HIV‐1 RNAs in inducing IL‐1β in humans. Abortive HIV‐1 RNAs were sensed by protein kinase RNA‐activated (PKR), which triggered activation of the canonical NLRP3 inflammasome and caspase‐1, leading to pro‐IL‐1β processing and secretion. PKR activated the inflammasome via ROS generation and MAP kinases ERK1/2, JNK, and p38. Inhibition of PKR during HIV‐1 infection blocked IL‐1β production. As abortive HIV‐1 RNAs are produced during productive infection and latency, our data strongly suggest that targeting PKR signaling might attenuate immune activation during acute and chronic HIV‐1 infection.
The effects of false identification laws on underage alcohol‐related traffic fatalities
Authors: Nesson Erik , Shrestha Vinish 
Published: July 2021

AbstractWe examine the effects of policies aimed at restricting the use of false identification to purchase alcohol on traffic fatalities involving alcohol‐impaired underage drivers. We find that the implementation of policies that incentivize alcohol retailers to adopt ID scanners reduces traffic fatalities from accidents involving 16–18 year old drivers with a BAC >0, but we do not find that similar policies like vertical ID laws lead to statistically significant changes in traffic fatalities involving underage impaired drivers. A back‐of‐the‐envelope calculation suggests that if all remaining states passed ID scanner laws, the reduction in underage alcohol‐related fatal accidents would generate over $400 million in annual economic benefits.
Differences in healthiness perceptions of food and dietary patterns among the general public and nutrition experts: A cross‐sectional online survey
Authors: Niven Philippa , Morley Belinda , Gascoyne Claudia , Dixon Helen , McAleese Alison , Martin Jane , Wakefield Melanie 
Published: July 2021

AbstractIssues addressedDiet quality plays a vital role in the prevention of prevalent non‐communicable diseases; however, misperceptions of healthiness of common foods and beverages may be undermining Australians’ attempts to maintain a healthy diet. The current study aimed to assess the extent and nature of differences in public and expert opinion in the foods, beverages and dietary patterns that are considered healthy.MethodsA cross‐sectional online survey of 1,097 Victorian adults aged 18‐64 and 134 professional dietitians and nutritionists assessed healthiness perceptions of foods, beverages and dietary patterns, self‐reported dietary patterns, and factors considered when making healthy choices. Differences in perceptions and dietary patterns between samples and by sex, socio‐economic area and level of education were assessed using multivariable logistic regression.ResultsThere were large discrepancies in which items the public and expert samples considered healthy. Females and those in high socio‐economic areas tended to report healthiness perceptions that aligned with the expert sample to a greater degree than their counterparts. Personal judgement of products was important to both samples when making decisions about healthy choices.ConclusionsThe public and expert samples differed greatly in healthiness perceptions with significant variation by demographics.So what?Well‐funded, sustained public health campaigns are needed to provide the public with evidence‐based health and nutrition information and combat persuasive, misleading messaging from popular media and marketing.
The government spending multiplier at the zero lower bound: International evidence from historical data
Authors: Klein Mathias , Winkler Roland 
Published: July 2021

SummaryBased on a large historical panel dataset, this paper provides evidence that the government spending multiplier can be significantly higher when interest rates are at or near the zero lower bound (ZLB). We estimate multipliers that are as high as 1.5 during ZLB episodes but small and statistically indistinguishable from zero during normal times. Our results are robust to different definitions of ZLB episodes, alternative ways of identifying government spending shocks, controlling for the exchange rate regime, and other potentially important state variables. In particular, we show that the difference in multipliers is not driven by multipliers being higher during periods of economic slack.
R‐loops mediate transcription‐associated formation of human rDNA secondary constrictions
Authors: Zhou Hong , Wang Yapei , Wang Qing , Li Le , Hu Yan , Wu Yequn , Gautam Mayank , Li Lijia 
Published: July 2021

AbstractThe ribosomal gene DNA (rDNA) often forms secondary constrictions in the chromosome; however, the molecular mechanism involved remains poorly understood. Here, we report that occurrence of rDNA constriction was increased in the chromosomes in human cancer cell lines compared with normal cells and that decondensed rDNA was significantly enhanced after partial inhibition of rDNA transcription. rDNA transcription was found during the S phase when replication occurred, and thus, DNA replication inhibitors caused constriction formation through hindering rDNA transcription. Inhibition of ataxia ATR (telangiectasia‐mutated and RAD3‐related) induced rDNA constriction formation. Replication stress or transcription inhibition increased R‐loop formation. Topoisomerase I and RNase H1 suppressed secondary constriction formation. These data demonstrate that transcription stress causes the accumulation of stable R‐loops (RNA–DNA hybrid) and subsequent constriction formation in the chromosomes.
Long‐term physical health outcomes of obsessive‐compulsive personality disorder traits
Authors: Morreale Michael , Holingue Calliope , Samuels Jack , Nestadt Gerald 
Published: July 2021

AbstractBackgroundObsessive‐compulsive personality disorder (OCPD) is characterized by pervasive and persistent traits including preoccupation with orderliness, perfectionism, and control. Relatively little is known about the potential relationship between OCPD traits and physical health.MethodsWe investigated the association between OCPD traits and several self‐reported medical conditions in 249 individuals followed prospectively from 1981 until 2004/2005 as part of the Epidemiological Catchment Area.ResultsThe OCPD trait score was inversely related to hypertension in males, in models unadjusted (OR = 0.66; 95% CI, 0.45–0.90) and adjusted (OR = 0.70; 95% CI, 0.47–0.95) for sociodemographic variables. Perfectionism was inversely related to hypertension in the unadjusted models for men (OR = 0.34; 95% CI, 0.12–0.89). Indecisiveness was positively associated with heart conditions in adjusted models for women (OR = 3.46; 95% CI, 1.11–10.52).ConclusionOCPD traits are associated with cardiovascular health in both sexes. Further studies are needed to understand the specificity of these relationships, as well as to determine the underlying mechanism.
Exosomes as drug delivery vehicles and biomarkers for neurological and auditory systems
Authors: Mittal Rahul , Bencie Nicole , Langlie Jake , Mittal Jeenu , Eshraghi Adrien A. 
Published: July 2021

AbstractExosomes are small extracellular membrane particles that play a crucial role in intracellular signaling. Research shows that exosomes have the potential to be used as biomarkers or drug delivery systems in specific organs, such as the neurological system and the inner ear. Exosomes in neurological and auditory systems release different molecules when under stress versus in healthy states, highlighting their potential use as biomarkers in the identification of diseased states. Studies have suggested that exosomes can be harnessed for drug delivery to hard‐to‐reach organs, such as cochlear sensory hair cells and the brain due to their ability to cross the blood‐labyrinth and blood‐brain barriers. In this article, we describe the biogenesis, classification, and characterization methods of exosomes. We then discuss recent studies that indicate their potential usage as biomarkers and drug delivery systems to help treat inner ear and neurological disorders.
Improvement of cardiac and systemic function in old mice by agonist of growth hormone‐releasing hormone
Authors: Xiang Pingping , Jing Wangwei , Lin Yinuo , Liu Qi , Shen Jian , Hu Xinyang , Chen Jinghai , Cai Renzhi , Hare Joshua M. , Zhu Wei , Schally Andrew V. , Yu Hong 
Published: July 2021

AbstractAge‐related diseases such as cardiovascular diseases portend disability, increase health expenditures, and cause late‐life mortality. Synthetic agonists of growth hormone‐releasing hormone (GHRH) exhibit several favorable effects on heart function and remodeling. Here we assessed whether GHRH agonist MR409 can modulate heart function and systemic parameters in old mice. Starting at the age of 15 months, mice were injected subcutaneously with MR409 (10 µg/day, n = 8) or vehicle (n = 7) daily for 6 months. Mice treated with MR409 showed improvements in exercise activity, cardiac function, survival rate, immune function, and hair growth in comparison with the controls. More stem cell colonies were grown out of the bone marrow recovered from the MR409‐treated mice. Mitochondrial functions of cardiomyocytes (CMs) from the MR409‐treated mice were also significantly improved with more mitochondrial fusion. Fewer β‐gal positive cells were observed in endothelial cells after 10 passages with MR409. In Doxorubicin‐treated H9C2 cardiomyocytes, cell senescence marker p21 and reactive oxygen species were significantly reduced after cultured with MR409. MR409 also improved cellular ATP production and oxygen consumption rate in Doxorubicin‐treated H9C2 cells. Mitochondrial protein OPA1 long isoform was significantly increased after treatment with MR409. The effects of MR409 were mediated by GHRH receptor and protein kinase A (PKA). In short, GHRH agonist MR409 reversed the aging‐associated changes with respect of heart function, mobility, hair growth, cellular energy production, and senescence biomarkers. The improvement of heart function may be related to a better mitochondrial functions through GHRH receptor/cAMP/PKA/OPA1 signaling pathway and relieved cardiac inflammation.
Fetuin‐A excess expression amplifies lipid induced apoptosis and β‐cell damage
Authors: Mukhuty Alpana , Fouzder Chandrani , Kundu Rakesh 
Published: July 2021

AbstractFetuin‐A, a hepato‐adipokine, is associated with lipid‐mediated islet inflammation and inflicts β‐cell death but the underlying mechanisms are still unclear. In an earlier report, it was shown that fetuin‐A promotes lipid‐induced insulin resistance by acting as an endogenous ligand of toll like receptor 4. Recently, we have also reported that β‐cells secrete fetuin‐A on stimulation by palmitate causing β‐cell dysfunction. The aim of this study was twofold: (a) screening the role of fetuin‐A in survival of murine β‐cells, and (b) to validate the effect of fetuin‐A release and lipid induced apoptosis in mouse insulinoma cell line MIN6. Excess of lipid and fetuin‐A in circulation induced significant deterioration of islet histoarchitecture and impeded insulin secretion by 2.7 ± 0.5‐folds in 20 weeks high fat diet mice. Administration of fetuin‐A (0.7 mg/g) along with 4 weeks of HFD produced similar results as 20 weeks of high fat feeding. Treating high doses of palmitate alone (0.50 mM) as well as in combination with fetuin‐A (100 µg/ml) for 24 h inflicted apoptosis in MIN6 through the mitochondrial pathway. Knockdown of fetuin‐A gene partially inhibited palmitate inflicted apoptosis in MIN6 by 1.83 ± 0.25 times, however, fetuin‐A when added in the medium caused re‐emergence of apoptosis. Notably, apoptosis induced by palmitate conditioned media from MIN6, 3T3L1, and HepG2, was partially inhibited in fetuin‐A KD MIN6. These results confirmed the critical role of circulatory fetuin‐A and β‐cell secreted fetuin‐A in β‐cell dysfunction and apoptosis under hyperlipidemic conditions.
Job satisfaction and stress among dental faculty members: A mixed‐method approach
Authors: PR GeethaPriya , Asokan Sharath , Viswanath Sudhandra 
Published: July 2021

AbstractObjectivesThe study aimed to assess job satisfaction and stress among dental faculty members. It was also planned to explore their experiences and probable solutions through a mixed‐method approach.MethodsSequential explanatory mixed‐method approach was employed. In the quantitative phase, a cross‐sectional web‐based questionnaire survey was conducted among dental faculty members in Tamil Nadu, India using the “Google Forms application” link. Based on Dentist Satisfaction Survey, a questionnaire was framed, validated, and used. It included 25 items under four domains (PICS): personal, institutional, cofaculty, and students. Mann–Whitney test was used to compare the differences between two independent groups. Kruskal–Wallis test and Friedman test were used for multiple group comparisons. In the qualitative phase one‐on‐one, semistructured telephone interviews were conducted among 27 dental faculties from various sectors.ResultA total of 408 participants took part in the quantitative survey. The students‐related domain was found to be the most dissatisfied or stressful domain (2.05±0.3) among dental faculties followed by the institutional domain (1.92±0.4) and cofaculty‐related domain (1.81±0.6). Based on qualitative interviews, four themes were derived namely (1) academia as a profession, (2) potential stressors, (3) sequelae of stress, and (4) stress‐free job.ConclusionThe present study provided deep insight into the stress among dental faculty members and emphasized the need for student–faculty mentor programs. It also stressed the importance of organized monetary structures or pay scales in private dental institutions in India.
Functional signals and covariation in triquetrum and hamate shape of extant primates using 3D geometric morphometrics
Authors: Vanhoof Marie J. M. , Galletta Lorenzo , De Groote Isabelle , Vereecke Evie E. 
Published: July 2021

AbstractIn this study, we want to investigate the covariation in the shape of two carpal bones, the triquetrum and hamate, and the possible association with locomotor behavior in a broad range of primate taxa. We applied 3D Geometric Morphometrics on a large data set comprising 309 anthropoid primates of 12 different genera. Principal component analyses were performed on the covariance matrix of 18 (triquetrum) and 23 (hamate) Procrustes‐aligned surface landmarks. A two‐block partial least square analysis was done to test the covariance between triquetrum and hamate shape, without relying on the predictive models implicit in regression analyses. The results show that the carpal shape of quadrupedal anthropoids, which mainly use their wrist under compressive conditions, differs from that of suspensory primates as their wrist is possibly subjected to tensile and torsional forces. Within the hominids, differences in shape also distinguish more terrestrial from more arboreal species. Even within the great apes, we are able to capture shape differences between species of the same genus. In combination with behavioral and biomechanical studies, the results of this research can be used to establish form‐function relationships of the primate hand which will aid the functional interpretation of primate fossil remains.