bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure
Authors: Parkes Linden , Moore Tyler M. , Calkins Monica E. , Cook Philip A. , Cieslak Matthew , Roalf David R. , Wolf Daniel H. , Gur Ruben C. , Gur Raquel E. , Satterthwaite Theodore D. , Bassett Danielle S. 
Published: April 2021

AbstractPsychopathology is rooted in neurodevelopment. However, clinical and biological heterogeneity, together with a focus on case-control approaches, have made it difficult to link dimensions of psychopathology to abnormalities of neurodevelopment. Here, using the Philadelphia Neurodevelopmental Cohort, we built normative models of cortical volume and tested whether deviations from these models better predicted psychiatric symptoms compared to raw cortical volume. Specifically, drawing on thep-factorhypothesis, we distilled 117 clinical symptom measures into six orthogonal psychopathology dimensions: overall psychopathology, anxious-misery, externalizing disorders, fear, positive psychosis symptoms, and negative psychosis symptoms. We found that multivariate patterns of deviations yielded improved out-of-sample prediction of psychopathology dimensions compared to multivariate patterns of raw cortical volume. We also found that correlations between overall psychopathology and deviations in ventromedial prefrontal, inferior temporal, and dorsal anterior cingulate cortices were stronger than those observed for specific dimensions of psychopathology (e.g., anxious-misery). Notably, these same regions are consistently implicated in a range of putatively distinct disorders. Finally, we performed conventional case-control comparisons of deviations in a group of individuals with depression and a group with attention-deficit hyperactivity disorder (ADHD). We observed spatially overlapping effects between these groups that diminished when controlling for overall psychopathology. Together, our results suggest that modeling cortical brain features as deviations from normative neurodevelopment improves prediction of psychiatric symptoms in out-of-sample testing, and thatp-factormodels of psychopathology may assist in separating biomarkers that are disorder-general from those that are disorder-specific.
Cross-sectional investigation of insulin resistance in youths with autism spectrum disorder. Any role for reduced brain glucose metabolism?
Authors: Manco Melania , Guerrera Silvia , Ravà Lucilla , Ciofi degli Atti Marta , Di Vara Silvia , Valeri Giovanni , Vicari Stefano 
Published: April 2021

AbstractThe autism spectrum disorder (ASD) is an etiologically heterogeneous disorder. Dysfunctions of the intermediate metabolism have been described in some patients. We speculate these metabolic abnormalities are associated with brain insulin resistance (IR), i.e., the reduced glucose metabolism at the level of the nervous central system. The Homeostasis model assessment of insulin resistance (HOMA-IR) is very often used in population studies as estimate of peripheral IR and it has been recently recognized as proxy of brain IR. We investigated HOMA-IR in 60 ASD patients aged 4–18 years and 240 healthy controls, also aged 4–18 years, but unmatched for age, sex, body weight, or body mass index (BMI). At multivariable linear regression model, the HOMA-IR was 0.31 unit higher in ASD individuals than in controls, after having adjusted for sex, age, BMI z-score category, and lipids that are factors known to influence HOMA-IR. Findings of this preliminary study suggest it is worth investigating brain glucose metabolism in larger population of patients with ASD by using gold standard technique. The recognition of a reduced glucose metabolism in some areas of the brain as marker of autism might have tremendous impact on our understanding of the pathogenic mechanisms of the disease and in terms of public health.
Deficits in hippocampal-dependent memory across different rodent models of early life stress: systematic review and meta-analysis
Authors: Rocha Mariana , Wang Daniel , Avila-Quintero Victor , Bloch Michael H. , Kaffman Arie 
Published: April 2021

AbstractExposure to early life stress (ELS) causes abnormal hippocampal development and functional deficits in rodents and humans, but no meta-analysis has been used yet to quantify the effects of different rodent models of ELS on hippocampal-dependent memory. We searched PubMed and Web of Science for publications that assessed the effects of handling, maternal separation (MS), and limited bedding and nesting (LBN) on performance in the Morris water maze (MWM), novel object recognition (NOR), and contextual fear conditioning (CFC). Forty-five studies met inclusion criteria (n = 451–763 rodents per test) and were used to calculate standardized mean differences (Hedge’s g) and to assess heterogeneity, publication bias, and the moderating effects of sex and species (rats vs. mice). We found significantly lower heterogeneity in LBN compared to handling and MS with no consistent effects of sex or species across the three paradigms. LBN and MS caused similar cognitive deficits in tasks that rely heavily on the dorsal hippocampus, such as MWM and NOR, and were significantly different compared to the improved performance seen in rodents exposed to handling. In the CFC task, which relies more on the ventral hippocampus, all three paradigms showed reduced freezing with moderate effect sizes that were not statistically different. These findings demonstrate the utility of using meta-analysis to quantify outcomes in a large number of inconsistent preclinical studies and highlight the need to further investigate the possibility that handling causes different alterations in the dorsal hippocampus but similar outcomes in the ventral hippocampus when compared to MS and LBN.
The transcriptional activator of the bfp operon in EPEC (PerA) interacts with the RNA polymerase alpha subunit
Authors: Lara-Ochoa Cristina , González-Lara Fabiola , Romero-González Luis E. , Jaramillo-Rodríguez Juan B. , Vázquez-Arellano Sergio I. , Medrano-López Abraham , Cedillo-Ramírez Lilia , Martínez-Laguna Ygnacio , Girón Jorge A. , Pérez-Rueda Ernesto , Puente José Luis , Ibarra J. Antonio 
Published: April 2021

AbstractEnteropathogenic E. coli virulence genes are under the control of various regulators, one of which is PerA, an AraC/XylS-like regulator. PerA directly promotes its own expression and that of the bfp operon encoding the genes involved in the biogenesis of the bundle-forming pilus (BFP); it also activates PerC expression, which in turn stimulates locus of enterocyte effacement (LEE) activation through the LEE-encoded regulator Ler. Monomeric PerA directly binds to the per and bfp regulatory regions; however, it is not known whether interactions between PerA and the RNA polymerase (RNAP) are needed to activate gene transcription as has been observed for other AraC-like regulators. Results showed that PerA interacts with the alpha subunit of the RNAP polymerase and that it is necessary for the genetic and phenotypic expression of bfpA. Furthermore, an in silico analysis shows that PerA might be interacting with specific alpha subunit amino acids residues highlighting the direction of future experiments.
Learning future terrorist targets through temporal meta-graphs
Authors: Campedelli Gian Maria , Bartulovic Mihovil , Carley Kathleen M. 
Published: April 2021

AbstractIn the last 20 years, terrorism has led to hundreds of thousands of deaths and massive economic, political, and humanitarian crises in several regions of the world. Using real-world data on attacks occurred in Afghanistan and Iraq from 2001 to 2018, we propose the use of temporal meta-graphs and deep learning to forecast future terrorist targets. Focusing on three event dimensions, i.e., employed weapons, deployed tactics and chosen targets, meta-graphs map the connections among temporally close attacks, capturing their operational similarities and dependencies. From these temporal meta-graphs, we derive 2-day-based time series that measure the centrality of each feature within each dimension over time. Formulating the problem in the context of the strategic behavior of terrorist actors, these multivariate temporal sequences are then utilized to learn what target types are at the highest risk of being chosen. The paper makes two contributions. First, it demonstrates that engineering the feature space via temporal meta-graphs produces richer knowledge than shallow time-series that only rely on frequency of feature occurrences. Second, the performed experiments reveal that bi-directional LSTM networks achieve superior forecasting performance compared to other algorithms, calling for future research aiming at fully discovering the potential of artificial intelligence to counter terrorist violence.
Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ-globin gene promoter
Authors: Nuamsee Khanita , Chuprajob Thipphawan , Pabuprapap Wachirachai , Jintaridth Pornrutsami , Munkongdee Thongperm , Phannasil Phatchariya , Vadolas Jim , Chaichompoo Pornthip , Suksamrarn Apichart , Svasti Saovaros 
Published: April 2021

AbstractThe reactivation of γ-globin chain synthesis to combine with excess free α-globin chains and form fetal hemoglobin (HbF) is an important alternative treatment for β-thalassemia. We had reported HbF induction property of natural curcuminoids, curcumin (Cur), demethoxycurcumin (DMC) and bis-demethoxycurcumin (BDMC), in erythroid progenitors. Herein, the HbF induction property of trienone analogs of the three curcuminoids in erythroleukemic K562 cell lines and primary human erythroid progenitor cells from β-thalassemia/HbE patients was examined. All three trienone analogs could induce HbF synthesis. The most potent HbF inducer in K562 cells was trienone analog of BDMC (T-BDMC) with 2.4 ± 0.2 fold increase. In addition, DNA methylation at CpG − 53, − 50 and + 6 of Gγ-globin gene promoter in K562 cells treated with the compounds including T-BDMC (9.3 ± 1.7%, 7.3 ± 1.7% and 5.3 ± 0.5%, respectively) was significantly lower than those obtained from the control cells (30.7 ± 3.8%, 25.0 ± 2.9% and 7.7 ± 0.9%, respectively P < 0.05). The trienone compounds also significantly induced HbF synthesis in β-thalassemia/HbE erythroid progenitor cells with significantly reduction in DNA methylation at CpG + 6 of Gγ-globin gene promoter. These results suggested that the curcuminoids and their three trienone analogs induced HbF synthesis by decreased DNA methylation at Gγ-globin promoter region, without effect on Aγ-globin promoter region.
Changing epidemiology and viral interplay of hepatitis B, C and D among injecting drug user-dominant prisoners in Taiwan
Authors: Lu Ming-Ying , Chen Chun-Ting , Shih Yu-Lueng , Tsai Pei-Chien , Hsieh Meng-Hsuan , Huang Chung-Feng , Yeh Ming-Lun , Huang Ching-I , Wang Shu-Chi , Tsai Yi-Shan , Ko Yu-Min , Lin Ching-Chih , Chen Kuan-Yu , Wei Yu-Ju , Hsu Po-Yao , Hsu Cheng-Ting , Jang Tyng-Yuan , Liu Ta-Wei , Liang Po-Cheng , Hsieh Ming-Yen , Lin Zu-Yau , Chen Shinn-Cherng , Huang Jee-Fu , Dai Chia-Yen , Chuang Wan-Long , Yu Ming-Lung , Chang Wen-Yu 
Published: April 2021

AbstractThe spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10–0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13–0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04–40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.
Association among extracellular superoxide dismutase genotype, plasma concentration, and comorbidity in the very old and centenarians
Authors: Sasaki Takashi , Abe Yukiko , Takayama Michiyo , Adachi Tetsuo , Okano Hideyuki , Hirose Nobuyoshi , Arai Yasumichi 
Published: April 2021

AbstractSuperoxide dismutase 3 (SOD3), an antioxidant enzyme, is known as extracellular SOD (EC-SOD) because it is the predominant form in extracellular fluids. The diversity of plasma EC-SOD concentration is associated with the SOD3 p.R231G missense variant genotype. To clarify the association among SOD3 genotype, plasma EC-SOD concentration, and comorbidity in Oldest Old, we analyzed genome-wide associations with plasma EC-SOD concentration and associations between EC-SOD concentration and medical history classified by the SOD3 genotype in the Very Old (85–99 years old, n = 505) and Centenarians (over 100 years old, n = 595). The results revealed that SOD3 p.R231G was the most significant variant associated with plasma EC-SOD concentration. Although no significant difference was observed in medical histories between the SOD3 p.R231G variant non-carriers and carriers, higher EC-SOD concentration in plasma of SOD3 p.R231G variant non-carriers was associated with a high odds ratio for chronic kidney disease (OR = 2.70, 95% CI = 1.98–3.72) and low odds ratio for diabetes mellitus (DM) (OR = 0.61, 95% CI = 0.39–0.95). Comparison with 11 plasma biomarkers for age-related disease showed that plasma EC-SOD concentration correlated with adiponectin and estimated glomerular filtration rate with creatinine correction; therefore, we deduced that EC-SOD co-operates with adiponectin and possesses beneficial functions for DM in the Oldest Old.
Enhanced inter-regional coupling of neural responses and repetition suppression provide separate contributions to long-term behavioral priming
Authors: Gotts Stephen J. , Milleville Shawn C. , Martin Alex 
Published: April 2021

AbstractStimulus identification commonly improves with repetition over long delays (“repetition priming”), whereas neural activity commonly decreases (“repetition suppression”). Multiple models have been proposed to explain this brain-behavior relationship, predicting alterations in functional and/or effective connectivity (Synchrony and Predictive Coding models), in the latency of neural responses (Facilitation model), and in the relative similarity of neural representations (Sharpening model). Here, we test these predictions with fMRI during overt and covert naming of repeated and novel objects. While we find partial support for predictions of the Facilitation and Sharpening models in the left fusiform gyrus and left frontal cortex, the data were most consistent with the Synchrony model, with increased coupling between right temporoparietal and anterior cingulate cortex for repeated objects that correlated with priming magnitude across participants. Increased coupling and repetition suppression varied independently, each explaining unique variance in priming and requiring modifications of all current models.
Optimal, near-optimal, and robust epidemic control
Authors: Morris Dylan H. , Rossine Fernando W. , Plotkin Joshua B. , Levin Simon A. 
Published: April 2021

AbstractIn the absence of drugs and vaccines, policymakers use non-pharmaceutical interventions such as social distancing to decrease rates of disease-causing contact, with the aim of reducing or delaying the epidemic peak. These measures carry social and economic costs, so societies may be unable to maintain them for more than a short period of time. Intervention policy design often relies on numerical simulations of epidemic models, but comparing policies and assessing their robustness demands clear principles that apply across strategies. Here we derive the theoretically optimal strategy for using a time-limited intervention to reduce the peak prevalence of a novel disease in the classic Susceptible-Infectious-Recovered epidemic model. We show that broad classes of easier-to-implement strategies can perform nearly as well as the theoretically optimal strategy. But neither the optimal strategy nor any of these near-optimal strategies is robust to implementation error: small errors in timing the intervention produce large increases in peak prevalence. Our results reveal fundamental principles of non-pharmaceutical disease control and expose their potential fragility. For robust control, an intervention must be strong, early, and ideally sustained.
Changes in the Gulf Stream preceded rapid warming of the Northwest Atlantic Shelf
Authors: Gonçalves Neto Afonso , Langan Joseph A. , Palter Jaime B. 
Published: April 2021

AbstractThe Northwest Atlantic Shelf provides ecological and economic benefits along the heavily populated North American coastline and beyond. In 2009-2010, abrupt warming prompted an ecosystem shift with consequences for fisheries, yet the cause of this event is unclear. Here we use satellite altimetry and in situ measurements to show that, in 2008, the Gulf Stream migrated closer to the Tail of the Grand Banks, a shift that has persisted ever since. This change reduced the westward connectivity of the Labrador Current that otherwise supplies cold, fresh, oxygen-rich waters to the shelf. Within one year after the appearance of anomalously warm and saline water at the Tail of Grand Banks, subsurface warming progressed south-westwards. Historical observations suggest a similar sequence of events may have occurred in the 1970s. Therefore, monitoring water properties at the Tail of Grand Banks may offer predictability for shelf properties and ecosystem perturbations with substantial lead time.
Seltene Erkrankungen in der Rheumatologie
Authors: Bauhammer Jutta , Fiehn Christoph 
Published: April 2021

ZUSAMMENFASSUNGAus der Rheumatologie sind seltene entzündliche Erkrankungen nicht wegzudenken. Ihre Therapie stellt den Rheumatologen/die Rheumatologin vor besondere Herausforderungen, da oft keine zugelassenen Medikamente existieren. Um aber im Off-Label-Einsatz zu behandeln, ist es notwendig, die Evidenz in der Behandlung der verschiedenen Erkrankungen gut zu kennen. In der folgenden Arbeit werden die Therapieoptionen sowohl zu In- wie auch Off-Label-Therapie der wichtigsten seltenen rheumatischen Erkrankungen der Erwachsenen dargestellt. Dies sind die systemische Sklerose, die idiopathischen inflammatorischen Myopathien, der Morbus Behçet, das familiäre Mittelmeerfieber, der Morbus Still, die idiopathische rekurrierende Perikarditis, das SAPHO-Syndrom, die chronisch rekurrierende multifokale und chronisch nicht bakterielle Osteomyelitis, die IgG4-Syndrome, die Mischkollagenose (Sharp-Syndrom) sowie die undifferenzierte und Overlap-Kollagenosen. Die klinischen Studien und aktuellen Empfehlungen zur Therapie dieser Erkrankungen, bezogen auch auf die jeweiligen Krankheitsmanifestationen, werden tabellarisch aufgelistet und die Referenzen genannt. Das Ziel des Artikels ist es, dem praktisch tätigen Rheumatologen eine Hilfestellung zur Auswahl der Therapie und unter Umständen auch der Beantragung einer Kostenübernahme für Off-Label-Therapien zu geben.
In-/Off-Label-Therapie bei rheumatoider Arthritis
Authors: Krüger Klaus 
Published: April 2021

ZUSAMMENFASSUNGLabelgerechter Einsatz von Medikamenten ist formaljuristisch und in Bezug auf Erstattungsfähigkeit einer Therapie wichtig – Off-Label-Therapie bedarf besonderer Aufklärungspflicht und birgt ein hohes Regress-Risiko. In der Rheumatologie ist vor allem bei Verschreibung kostenintensiver Medikamente wie Biologika und JAK-Inhibitoren auf labelgerechten Einsatz zu achten. Hierbei stehen – neben der Voraussetzung einer Zulassung für die rheumatoide Arthritis (RA) – 3 Risikobereiche im Mittelpunkt: Richtiger Zeitpunkt des Einsatzes, korrekte Dosierung und Mono- bzw. Kombinationstherapie. Der Zeitpunkt betrifft die Frage, ob eine Substanz im Therapie-Algorithmus als First-, Second- oder sogar Third-Line-Therapie (Rituximab) zugelassen ist. Bei der Dosierung ist darauf zu achten, dass die oberste zugelassene Dosis nicht überschritten wird. Zwar stellt formell auch Unterschreitung der Zulassungsdosis einen Off-Label-Einsatz dar, bleibt jedoch in der Regel ohne Konsequenzen. Da DMARD z. T. nur in Kombination mit Methotrexat (Mtx) zugelassen sind, liegt auch hier ein Fallstrick, ebenso bei Verwendung anderer Kombinationspartner als Mtx. Die vorliegende Übersicht bemüht sich, dem Verordner Hilfestellung für eine sichere Anwendung vor allem der DMARD-Therapie zu geben.
Disparities in Trial of Labor among Women with Twin Gestations in the United States
Authors: Mo Gina N. , Cheng Yvonne W. , Caughey Aaron B. , Yee Lynn M. 
Published: April 2021

Objective The aim of the study is to examine clinical and demographic factors associated with trial of labor (TOL) among women with twin gestations eligible for a vaginal delivery.
Study Design This was a population-based cohort study of women giving birth to twin gestations in the United States (2012–2014). Inclusion criteria for the analysis included live births greater than 23 weeks' gestation and a cephalic presenting twin. Women with prior cesarean delivery were excluded. Women were categorized by whether they underwent a TOL. Clinical and demographic characteristics associated with TOL status were evaluated using multivariable logistic regression analyses. Secondary analyses with stratification by parity and by second twin presentation were performed.
Results Of 90,000 women eligible for inclusion, a minority (39.3%) underwent TOL. Women who had a greater gestational age at delivery were more likely to have a TOL. In contrast, several demographic factors were associated with decreased likelihood of TOL, including maternal age >35 years and identifying as Hispanic or Asian compared with non-Hispanic White. No differences in odds of TOL were observed for women who were identified as non-Hispanic Black versus non-Hispanic White, nor were other demographic factors such as marital status, insurance status, or educational attainment associated with undergoing TOL. Clinical factors associated with decreased odds of TOL included nulliparity, obesity, and hypertensive disorders of pregnancy. Results did not substantively change when stratified by parity or second twin presentation, nor did findings differ in the subgroup who delivered at 32 weeks of gestation or greater.
Conclusion In this large population of women with twins who were eligible for a TOL, a minority of individuals attempted a vaginal delivery. Demographic and clinical factors such as older maternal age, Asian or Hispanic racial or ethnic identification, nulliparity, and obesity are associated with decreased odds of undergoing TOL.
Key Points