bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do implicit measures improve suicide risk prediction? An 18‐month prospective study using different tasks
Authors: Scheunemann Jakob , Jelinek Lena , Peth Judith , Runde Anne , Arlt Sönke , Gallinat Jürgen , Kühn Simone 
Published: July 2021

AbstractBackgroundThere is accumulating evidence that implicit measures improve the prediction of suicidality within a 6‐month follow‐up period in psychiatric populations. Building upon these results, we set out to expand the follow‐up period and to investigate various implicit methods.MethodsSeventy‐nine inpatients completed the Beck Scale for Suicidal Ideation (BSS) and a range of implicit measures: three implicit association tests (IATs: Death; Self‐harm–Me/Others; Self‐Harm–Good/Bad) and a subliminal priming task (with separate scores for negative and positive adjectives, each indicating the association between the primes “dying” and “growing”). After 18 months, we reached n = 52 patients and reassessed suicidal ideation, plans, and attempts.ResultsIn a hierarchical regression, the five implicit task indices were entered after the patient's age, gender, and BSS score at baseline. The implicit scores improved prediction of BSS scores after 18 months compared to prediction based on age, gender, and BSS score at baseline alone. However, none of the implicit measures was associated with suicide plans or attempts during the follow‐up period.ConclusionResults suggest that implicit measures can be a useful assessment tool for the prediction of suicidal ideation, even beyond the BSS. However, long‐term prediction of suicide plans or attempts using implicit measures seems limited.
Repeated bouts of resistance exercise in rats alter mechanistic target of rapamycin complex 1 activity and ribosomal capacity but not muscle protein synthesis
Authors: Kotani Takaya , Takegaki Junya , Tamura Yuki , Kouzaki Karina , Nakazato Koichi , Ishii Naokata 
Published: July 2021

New Findings

What is the central question of this study?
Is muscle protein synthesis (MPS) additionally activated following exercise when ribosomal capacity is increased after repeated bouts of resistance exercise (RE)?

What is the main finding and its importance?
Skeletal muscles with increased ribosome content through repeated RE bouts showed sufficient activation of MPS with lower mechanistic target of rapamycin complex 1 signalling. Thus, repeated bouts of RE possibly change the translational capacity and efficiency to optimize translation activation following RE.

AbstractResistance exercise (RE) activates ribosome biogenesis and increases ribosome content in skeletal muscles. However, it is unclear whether the increase in ribosome content subsequently causes an increase in RE‐induced activation of muscle protein synthesis (MPS). Thus, this study aimed to investigate the relationship between ribosome content and MPS after exercise using a rat RE model. Male Sprague–Dawley rats were categorized into three groups (n = 6 for each group): sedentary (SED) and RE trained with one bout (1B) or three bouts (3B). The RE stimulus was applied to the right gastrocnemius muscle by transcutaneous electrical stimulation under isoflurane anaesthesia. The 3B group underwent stimulation every other day. Our results revealed that 6 h after the last bout of RE, muscles in the 3B group showed an increase in total RNA and 18S+28S rRNA content per muscle weight compared with the SED and 1B groups. In both the 1B and 3B groups, MPS, estimated by puromycin incorporation in proteins, was higher than that in the SED group 6 h after exercise; however, no significant difference was observed between the 1B and 3B groups. In the 1B and 3B groups, phosphorylated p70S6K at Thr‐389 increased, indicating mechanistic target of rapamycin complex 1 (mTORC1) activity. p70S6K phosphorylation level was lower in the 3B group than in the 1B group. Finally, protein synthesis per ribosome (indicator of translation efficiency) was lower in the 3B group than in the 1B group. Thus, three bouts of RE changed the ribosome content and mTORC1 activation, but not the degree of RE‐induced global MPS activation.
Forced subduction initiation within the Neotethys: An example from the mid-Cretaceous Wuntho-Popa arc in Myanmar
Authors: Zhang Liyun , Fan Weiming , Ding Lin , Pullen Alex , Ducea Mihai N. , Li Jinxiang , Wang Chao , Xu Xiaoyan , Sein Kyaing 
Published: July 2021

Abstract
Despite decades of research, the mechanisms and processes of subduction initiation remain obscure, including the tectonic settings where subduction initiation begins and how magmatism responds. The Cretaceous Mawgyi Volcanics represent the earliest volcanic succession in the Wuntho-Popa arc of western Myanmar. This volcanic unit consists of an exceptionally diverse range of contemporaneously magmatic compositions which are spatially juxtaposed. Our new geochemical data show that the Mawgyi Volcanics comprise massive mid-oceanic ridge basalt (MORB)-like lavas and dikes, and subordinate island arc tholeiite and calc-alkaline lavas. The Mawgyi MORB-like rocks exhibit flat rare earth elements (REEs) patterns and are depleted in REEs, high field strength elements (except for Th) and TiO2 concentrations relative to those of MORBs, resembling the Izu-Bonin-Mariana protoarc basalts. Our geochronological results indicate that the Mawgyi Volcanics formed between 105 and 93 Ma, coincident with formation of many Neotethyan supra-subduction zone ophiolites and intraoceanic arcs along orogenic strike in the eastern Mediterranean, Middle East, Pakistan, and Southeast Asia. Combined with its near-equatorial paleo-latitudes constrained by previous paleomagnetic data, the Wuntho-Popa arc is interpreted as a segment of the north-dipping trans-Neotethyan subduction system during the mid-Cretaceous. Importantly, our restoration with available data provides new evidence supporting the hypothesis of a mid-Cretaceous initiation of this &gt;8000-km-long subduction system formed by inversion of the ∼E-W–trending Neotethyan oceanic spreading ridges, and that this was contemporaneous with the final breakup of Gondwana and an abrupt global plate reorganization.
Exploring the association of social determinants of health and clinical quality measures and performance in HRSA-funded health centres
Authors: Topmiller Michael , McCann Jessica , Rankin Jennifer , Hoang Hank , Bolton Joshua , Sripipatana Alek 
Published: July 2021

ObjectiveThis paper explores the impact of service area-level social deprivation on health centre clinical quality measures.DesignCross-sectional data analysis of Health Resources and Services Administration (HRSA)-funded health centres. We created a weighted service area social deprivation score for HRSA-funded health centres as a proxy measure for social determinants of health, and then explored adjusted and unadjusted clinical quality measures by weighted service area Social Deprivation Index quartiles for health centres.SettingsHRSA-funded health centres in the USA.ParticipantsOur analysis included a subset of 1161 HRSA-funded health centres serving more than 22 million mostly low-income patients across the country.ResultsHigher levels of social deprivation are associated with statistically significant poorer outcomes for all clinical quality outcome measures (both unadjusted and adjusted), including rates of blood pressure control, uncontrolled diabetes and low birth weight. The adjusted and unadjusted results are mixed for clinical quality process measures as higher levels of social deprivation are associated with better quality for some measures including cervical cancer screening and child immunisation status but worse quality for other such as colorectal cancer screening and early entry into prenatal care.ConclusionsThis research highlights the importance of incorporating community characteristics when evaluating clinical outcomes. We also present an innovative method for capturing health centre service area-level social deprivation and exploring its relationship to health centre clinical quality measures.
Trends in the prevalence and incidence of anxiety and depressive symptoms in Iran: findings from KERCADRS
Authors: Najafipour Hamid , Shahrokhabadi Mohadeseh Shojaei , Banivaheb Ghodsyeh , Sabahi Abdolreza , Shadkam Mitra , Mirzazadeh Ali 
Published: July 2021

ObjectivesAnxiety and depression (A&D) are common mental disorders with high economical and health burdens. This study aimed to investigate the prevalence and the incidence rate of A&D symptoms and their relationship with sociodemographic and other risk factors and comorbidities in adults living in southeastern Iran.DesignA population-based cohort study with random cluster household survey sampling method.SettingSecond round of Kerman Coronary Artery Disease Risk Factors Study (KERCADRS) (2014–2018) performed in Southeastern, Iran.ParticipantsWe recruited 9997 participants (15–80 years) in the second round of the study, from whom 2820 persons were the people who also participated in the first round of KERCADRS in 2009–2012. The age-standardised A&D prevalence was measured among all participants, and the 5-year A&D incidence rate was measured in those who were free from A&D in the first round in 2009–2012 and were at risk of A&D in the follow-up. The relationship between A&D and demographic characteristics, smoking, opium use, obesity and physical activity was assessed by logistic regression models.ResultsOverall, the prevalence of anxiety (48.1% to 16.4%, p<0.001) and depression (5.9% to 1.3%, p<0.001) decreased between the two rounds. The highest prevalence of anxiety was among widowed (31.4%), unemployed (21.3%), obese (19.4%), and opium users (17.4%). Young adults, women, those divorced or widowed, and those with obesity and low physical activity had a higher chance of developing anxiety. The 5-year incidence rate (person/1000 person-years) was 15.0 for anxiety and 3.9 for depression.ConclusionDespite the overall decrease in the prevalence of A&D symptoms in last 5 years in the area, young adults, women, unemployed, opium users, people with low physical activity and those with obesity had a higher chance of developing anxiety and are in need of more targeted interventions.
TET2 and DNMT3A Mutations Exert Divergent Effects on DNA Repair and Sensitivity of Leukemia Cells to PARP Inhibitors
Authors: Maifrede Silvia , Le Bac Viet , Nieborowska-Skorska Margaret , Golovine Konstantin , Sullivan-Reed Katherine , Dunuwille Wangisa M.B. , Nacson Joseph , Hulse Michael , Keith Kelsey , Madzo Jozef , Caruso Lisa Beatrice , Gazze Zachary , Lian Zhaorui , Padella Antonella , Chitrala Kumaraswamy N. , Bartholdy Boris A. , Matlawska-Wasowska Ksenia , Di Marcantonio Daniela , Simonetti Giorgia , Greiner Georg , Sykes Stephen M. , Valent Peter , Paietta Elisabeth M. , Tallman Martin S. , Fernandez Hugo F. , Litzow Mark R. , Minden Mark D. , Huang Jian , Martinelli Giovanni , Vassiliou George S. , Tempera Italo , Piwocka Katarzyna , Johnson Neil , Challen Grant A. , Skorski Tomasz 
Published: July 2021

Abstract

Somatic variants in TET2 and DNMT3A are founding mutations in hematological malignancies that affect the epigenetic regulation of DNA methylation. Mutations in both genes often co-occur with activating mutations in genes encoding oncogenic tyrosine kinases such as FLT3ITD, BCR-ABL1, JAK2V617F, and MPLW515L, or with mutations affecting related signaling pathways such as NRASG12D and CALRdel52. Here, we show that TET2 and DNMT3A mutations exert divergent roles in regulating DNA repair activities in leukemia cells expressing these oncogenes. Malignant TET2-deficient cells displayed downregulation of BRCA1 and LIG4, resulting in reduced activity of BRCA1/2-mediated homologous recombination (HR) and DNA-PK–mediated non-homologous end-joining (D-NHEJ), respectively. TET2-deficient cells relied on PARP1-mediated alternative NHEJ (Alt-NHEJ) for protection from the toxic effects of spontaneous and drug-induced DNA double-strand breaks. Conversely, DNMT3A-deficient cells favored HR/D-NHEJ owing to downregulation of PARP1 and reduction of Alt-NHEJ. Consequently, malignant TET2-deficient cells were sensitive to PARP inhibitor (PARPi) treatment in vitro and in vivo, whereas DNMT3A-deficient cells were resistant. Disruption of TET2 dioxygenase activity or TET2—Wilms' tumor 1 (WT1)–binding ability was responsible for DNA repair defects and sensitivity to PARPi associated with TET2 deficiency. Moreover, mutation or deletion of WT1 mimicked the effect of TET2 mutation on DSB repair activity and sensitivity to PARPi. Collectively, these findings reveal that TET2 and WT1 mutations may serve as biomarkers of synthetic lethality triggered by PARPi, which should be explored therapeutically.

Significance:
TET2 and DNMT3A mutations affect distinct DNA repair mechanisms and govern the differential sensitivities of oncogenic tyrosine kinase–positive malignant hematopoietic cells to PARP inhibitors.
Nonsense-Mediated RNA Decay Is a Unique Vulnerability of Cancer Cells Harboring SF3B1 or U2AF1 Mutations
Authors: Cheruiyot Abigael , Li Shan , Nonavinkere Srivatsan Sridhar , Ahmed Tanzir , Chen Yuhao , Lemacon Delphine S. , Li Ying , Yang Zheng , Wadugu Brian A. , Warner Wayne A. , Pruett-Miller Shondra M. , Obeng Esther A. , Link Daniel C. , He Dalin , Xiao Fei , Wang Xiaowei , Bailis Julie M. , Walter Matthew J. , You Zhongsheng 
Published: July 2021

Abstract

Nonsense-mediated RNA decay (NMD) is recognized as an RNA surveillance pathway that targets aberrant mRNAs with premature translation termination codons (PTC) for degradation, however, its molecular mechanisms and roles in health and disease remain incompletely understood. In this study, we developed a novel reporter system to accurately measure NMD activity in individual cells. A genome-wide CRISPR-Cas9 knockout screen using this reporter system identified novel NMD-promoting factors, including multiple components of the SF3B complex and other U2 spliceosome factors. Interestingly, cells with mutations in the spliceosome genes SF3B1 and U2AF1, which are commonly found in myelodysplastic syndrome (MDS) and cancers, have overall attenuated NMD activity. Compared with wild-type (WT) cells, SF3B1- and U2AF1-mutant cells were more sensitive to NMD inhibition, a phenotype that is accompanied by elevated DNA replication obstruction, DNA damage, and chromosomal instability. Remarkably, the sensitivity of spliceosome mutant cells to NMD inhibition was rescued by overexpression of RNase H1, which removes R-loops in the genome. Together, these findings shed new light on the functional interplay between NMD and RNA splicing and suggest a novel synthetic lethal strategy for the treatment of MDS and cancers with spliceosome mutations.

Significance:
This study has developed a novel NMD reporter system and identified a potential therapeutic approach of targeting the NMD pathway to treat cancer with spliceosome gene mutations.
Development of a Novel Mouse Model of Spontaneous High-Risk HPVE6/E7–Expressing Carcinoma in the Cervicovaginal Tract
Authors: Henkle Talia R. , Lam Brandon , Kung Yu Jui , Lin John , Tseng Ssu-Hsueh , Ferrall Louise , Xing Deyin , Hung Chien-Fu , Wu T.-C. 
Published: July 2021

AbstractCurrent preclinical models for cervical cancer lack important clinical and pathologic features. To improve upon these models, we aimed to develop a novel, spontaneous HPV16-expressing carcinoma model that captures major aspects of HPV-associated cancer in the female genital tract. This novel preclinical model features (i) expression of HPV oncogenes E6 and E7 in the tumors in female reproductive tract of mice, (ii) spontaneous progression through high-grade squamous intraepithelial lesion (HSIL) to carcinoma, and (iii) flexibility to model cancers from different high-risk HPV genotypes. This was accomplished by injecting plasmids expressing HPV16 E6/E7-luciferase, AKT, c-myc, and Sleeping Beauty transposase into the cervicovaginal tract of C57BL/6 mice followed by electroporation. Cell lines derived from these tumors expressed HPV16 E6/E7 oncogenes, formed tumors in immunocompetent mice, and displayed carcinoma morphology. In all, this novel HPV-associated cervicogenital carcinoma model and HPV16E6/E7–expressing tumor cell line improves upon current HPV16-E6/E7–expressing tumor models. These tumor models may serve as important preclinical models for the development of therapeutic HPV vaccines or novel therapeutic interventions against HPV E6/E7–expressing tumors.Significance:This study describes the development of a clinically relevant mouse model of cervicovaginal carcinoma that progresses from high-grade lesions and recapitulates key features of human HPV+ cervical cancer.
Abstract 1680: Notch Signaling Directly Targets Msx2: Possible Role of Notch Signaling in Osteogenic Conversion of Vascular Smooth Muscle Cells and Vascular Calcification
Authors: Shimizu Takehisa , Tanaka Toru , Iso Tatsuya , Kurabayashi Masahiko 
Published: July 2021

Vascular calcification is a prominent feature of atherosclerosis and closely correlated with cardiovascular morbidity and mortality. In this study, we hypothesize that Notch signaling plays an important role in osteogenic conversion of smooth muscle cells (SMCs) and vascular calcification.
<Methods and Results> Either Notch ligand-expressing cells or overexpression of Notch intracellular domains (NICDs) induced expression of Msx2, a key regulator of osteogenic conversion, in human aortic SMCs (HASMCs). In addition, overexpression of Notch1 intracellular domain (N1-ICD) markedly upregulated alkaline phosphatase (ALP) activity and matrix mineralization of HASMCs. A knockdown experiment with a small interfering RNA confirmed that Msx2, but not Runx2/Cbfa1, another key osteogenic transcription factor, is responsible for Notch1-induced osteogenic conversion of HASMCs. Furthermore, this Notch1-Msx2 pathway was independent of bone morphogenetic protein-2 (BMP-2), an osteogenic morphogen upstream of Msx2. The transcriptional activity of the Msx2 promoter was significantly enhanced by Notch ligands stimulation, whereas it was abrogated by a specific Notch signaling inhibitor. The RBP-Jk binding element within the Msx2 promoter was critical to Notch1-induced Msx2 gene expression, and correspondingly, neither N1-ICD overexpression nor Notch ligands stimulation increase the Msx2 expression or transcriptional activity of the Msx2 promoter, respectively, in RBP-Jk-deficient fibroblasts. Immunohistochemistry of human artery specimens revealed colocalization of Notch1 and Msx2 within atherosclerotic plaques, indicating a role of Notch1-Msx2 pathway in vascular calcification in vivo. These results suggest that Notch signaling directly targets Msx2, thus accelerating osteogenic conversion of HASMCs and, as a result, a formation of vascular calcification.
Abstract P061: Determinants of Incident Metabolic Syndrome and Type 2 Diabetes in Normal Weight: The Jackson Heart Study
Authors: Mongraw-Chaffin Morgana , Saldana Santiago , Carnethon Mercedes R , Chen Haiying , Effoe Valery S , Golden Sherita H , Joseph Joshua J , Kalyani Rita R , Norwood Arnita , Bertoni Alain G 
Published: July 2021

New evidence suggests that individuals with normal weight at diagnosis of type 2 diabetes (T2D) are at higher risk for all-cause mortality than those who were overweight or obese at diagnosis. While investigation of the determinants of different diabetes risk categories among those with obesity has become more common, explanations beyond genetic predisposition for the heterogeneity in risk among those without obesity are lacking. We hypothesized that visceral fat and insulin resistance would be associated with incident metabolic syndrome (MetS) and T2D among African American individuals with normal weight.

In 1,032 participants of the Jackson Heart Study with normal weight (BMI 18.5 – 24.9 kg/m
2
), we used logistic regression to investigate the determinants of incident MetS and T2D, separately. T2D and MetS were assessed at study visit 3 for the CT scan variables, and visits 2 and 3 for all other variables. We used the harmonized International Diabetes Federation criteria to define MetS. We excluded participants with prevalent MetS or T2D, and those with missing exposure or outcome data.

Normal weight participants with MetS or T2D were more likely to be older, male, have lower socioeconomic status, caloric, fiber, saturated fat intake, and higher CRP and visceral fat. Higher HOMA-IR and subcutaneous fat were seen only in those with MetS. Higher visceral fat, subcutaneous fat, BMI, and HOMA-IR were significantly associated with incident MetS after adjustment for age, sex, education, and income (Figure). Only visceral fat and HOMA-IR were significantly associated with incident T2D. Estimates for BMI, but not visceral fat, were strongly attenuated with mutual adjustment. Physical activity was not associated with MetS or T2D in any model.
In conclusion, visceral fat is more strongly associated with incident MetS and T2D than subcutaneous fat or physical activity, even in normal weight individuals, suggesting that
adiposity plays a role in the development of cardiometabolic dysfunction even in the absence of obesity.
A Struggle for Institutionalization: the Tunisian Assemblée des Répresentants du Peuple and the Dominance of Consensus-Oriented Politics
Authors: Bahri Chahd , Völkel Jan Claudius 
Published: July 2021

Abstract
This article is part of the Special Issue “Parliaments in the Middle East and North Africa: A Struggle for Relevance.” Tunisia’s parliament has undergone a remarkable internal transformation process since 2011, from a formerly mostly irrelevant institution to an influential locus of policy-making. This successful progress notwithstanding, the parliament’s transformation to a democratic assembly has not been fully concluded yet. A main challenge is that the legislature still shows a number of characteristics of an “authoritarian parliament”: besides a lack of staff and financial resources, the continuous dominance of personal kinship over institutionalized power structures remains particularly problematic.
While private networks of individual decision-makers were perceived as crucial for Tunisia’s stability during the turbulent post-revolution years, they concomitantly contain the risk for a resurrection of former authoritarian structures. The article thus traces the Tunisian parliament’s major transformation steps from a former irrelevant legislature to a consolidated, influential assembly, and points out the still existing challenges.
Crosslinguistic Image Schema Differential Hypothesis Clarifies Non-Prototypical and Polysemous Spatial Preposition ‘on’ for L2 Learners
Authors: Taferner Robert H. , Yamada Jun 
Published: July 2021

Abstract
A key question for linguistics involves how to determine and account for expressions of non-prototypical spatial relationships between languages. To address this issue, Crosslinguistic Image Schema Differential (CISD) hypothesis is introduced to examine various uses of the English preposition on produced by L2 (second language) learners. Data collection consisted of a grammar test designed to elicit and measure participants’ knowledge of the English preposition on by completing cloze sentences in English, translating these sentences into the L1 (first language), and then drawing visual images of the sentences presented as redescriptions of perceptual events, i.e., image schemas. The most remarkable findings were that two space-relational types (‘encirclement with contact’ and ‘at an edge’) and one image schema (‘concave surface’) were almost completely lacking in the Japanese learners of English (JLEs) who participated in this study. This investigation indicates that simple explicit explanations are possible utilizing the CISD hypothesis.