bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transdiagnostic individualized clinically-based risk calculator for the automatic detection of individuals at-risk and the prediction of psychosis: external replication in 2,430,333 US patients
Authors: Oliver Dominic , Wong Chiew Meng Johnny , Bøg Martin , Jönsson Linus , Kinon Bruce J. , Wehnert Allan , Jørgensen Kristian Tore , Irving Jessica , Stahl Daniel , McGuire Philip , Raket Lars Lau , Fusar-Poli Paolo 
Published: October 2020

AbstractThe real-world impact of psychosis prevention is reliant on effective strategies for identifying individuals at risk. A transdiagnostic, individualized, clinically-based risk calculator to improve this has been developed and externally validated twice in two different UK healthcare trusts with convincing results. The prognostic performance of this risk calculator outside the UK is unknown. All individuals who accessed primary or secondary health care services belonging to the IBM® MarketScan® Commercial Database between January 2015 and December 2017, and received a first ICD-10 index diagnosis of nonorganic/nonpsychotic mental disorder, were included. According to the risk calculator, age, gender, ethnicity, age-by-gender, and ICD-10 cluster diagnosis at index date were used to predict development of any ICD-10 nonorganic psychotic disorder. Because patient-level ethnicity data were not available city-level ethnicity proportions were used as proxy. The study included 2,430,333 patients with a mean follow-up of 15.36 months and cumulative incidence of psychosis at two years of 1.43%. There were profound differences compared to the original development UK database in terms of case-mix, psychosis incidence, distribution of baseline predictors (ICD-10 cluster diagnoses), availability of patient-level ethnicity data, follow-up time and availability of specialized clinical services for at-risk individuals. Despite these important differences, the model retained accuracy significantly above chance (Harrell’s C = 0.676, 95% CI: 0.672–0.679). To date, this is the largest international external replication of an individualized prognostic model in the field of psychiatry. This risk calculator is transportable on an international scale to improve the automatic detection of individuals at risk of psychosis.
Antihypertensive drugs are associated with reduced fatal outcomes and improved clinical characteristics in elderly COVID-19 patients
Authors: Yan Feifei , Huang Fengming , Xu Jun , Yang Penghui , Qin Yuhao , Lv Jingjun , Zhang Shaogeng , Ye Lu , Gong Ming , Liu Zhibo , Wei Jie , Xie Tuxiu , Xu Kai-Feng , Gao George F. , Wang Fu-Sheng , Cai Lin , Jiang Chengyu 
Published: October 2020

AbstractThe novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak began at the end of 2019 in Wuhan, China, and has spread to over 200 countries. In this multicenter retrospective study, we identified 2190 adult patients admitted for laboratory-confirmed COVID-19 in three participating centers. Multivariate logistic regression was conducted in patients with comorbid hypertension to examine the potential association between clinical outcomes, disease severity, and clinical characteristics with the use of ACEI, ARB, calcium-channel blockers (CCB), beta-blockers (BB), and thiazide diuretics. The clinical outcome, dyspnea, and fatigue were significantly improved in patients, especially elderly patients who were older than 65 years, who took ARB drugs prior to hospitalization compared to patients who took no drugs. The reduction of disease severity of elderly COVID-19 patients was associated with CCB and ACEI users. Clinical indices, including CRP, lymphocyte count, procalcitonin D dimer, and hemoglobin, were significantly improved in elderly ARB users. In addition, the clinical outcomes were statistically significantly improved in patients who took antihypertension drugs ARB, BB, and CCB after statistical adjustment by all ages, gender, baseline of blood pressures, and coexisting medical conditions. Our data indicate that hypertension drugs ARB, ACEI, CCB, and BB might be beneficial for COVID-19 patients.
Graphene memristive synapses for high precision neuromorphic computing
Authors: Schranghamer Thomas F. , Oberoi Aaryan , Das Saptarshi 
Published: October 2020

AbstractMemristive crossbar architectures are evolving as powerful in-memory computing engines for artificial neural networks. However, the limited number of non-volatile conductance states offered by state-of-the-art memristors is a concern for their hardware implementation since trained weights must be rounded to the nearest conductance states, introducing error which can significantly limit inference accuracy. Moreover, the incapability of precise weight updates can lead to convergence problems and slowdown of on-chip training. In this article, we circumvent these challenges by introducing graphene-based multi-level (>16) and non-volatile memristive synapses with arbitrarily programmable conductance states. We also show desirable retention and programming endurance. Finally, we demonstrate that graphene memristors enable weight assignment based on k-means clustering, which offers greater computing accuracy when compared with uniform weight quantization for vector matrix multiplication, an essential component for any artificial neural network.
Expanding detection windows for discriminating single nucleotide variants using rationally designed DNA equalizer probes
Authors: Wang Guan A. , Xie Xiaoyu , Mansour Hayam , Chen Fangfang , Matamoros Gabriela , Sanchez Ana L. , Fan Chunhai , Li Feng 
Published: October 2020

AbstractCombining experimental and simulation strategies to facilitate the design and operation of nucleic acid hybridization probes are highly important to both fundamental DNA nanotechnology and diverse biological/biomedical applications. Herein, we introduce a DNA equalizer gate (DEG) approach, a class of simulation-guided nucleic acid hybridization probes that drastically expand detection windows for discriminating single nucleotide variants in double-stranded DNA (dsDNA) via the user-definable transformation of the quantitative relationship between the detection signal and target concentrations. A thermodynamic-driven theoretical model was also developed, which quantitatively simulates and predicts the performance of DEG. The effectiveness of DEG for expanding detection windows and improving sequence selectivity was demonstrated both in silico and experimentally. As DEG acts directly on dsDNA, it is readily adaptable to nucleic acid amplification techniques, such as polymerase chain reaction (PCR). The practical usefulness of DEG was demonstrated through the simultaneous detection of infections and the screening of drug-resistance in clinical parasitic worm samples collected from rural areas of Honduras.
Light-induced primary amines and o-nitrobenzyl alcohols cyclization as a versatile photoclick reaction for modular conjugation
Authors: Guo An-Di , Wei Dan , Nie Hui-Jun , Hu Hao , Peng Chengyuan , Li Shao-Tong , Yan Ke-Nian , Zhou Bin-Shan , Feng Lei , Fang Chao , Tan Minjia , Huang Ruimin , Chen Xiao-Hua 
Published: October 2020

AbstractThe advent of click chemistry has had a profound impact on many fields and fueled a need for reliable reactions to expand the click chemistry toolkit. However, developing new systems to fulfill the click chemistry criteria remains highly desirable yet challenging. Here, we report the development of light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) as a photoclick reaction via primary amines as direct click handle, to rapid and modular functionalization of diverse small molecules and native biomolecules. With intrinsic advantages of temporal control, good biocompatibility, reliable chemoselectivity, excellent efficiency, readily accessible reactants, operational simplicity and mild conditions, the PANAC photoclick is robust for direct diversification of pharmaceuticals and biorelevant molecules, lysine-specific modifications of unprotected peptides and native proteins in vitro, temporal profiling of endogenous kinases and organelle-targeted labeling in living systems. This strategy provides a versatile platform for organic synthesis, bioconjugation, medicinal chemistry, chemical biology and materials science.
Controlling the dimension of the quantum resonance in CdTe quantum dot superlattices fabricated via layer-by-layer assembly
Authors: Lee TaeGi , Enomoto Kazushi , Ohshiro Kazuma , Inoue Daishi , Kikitsu Tomoka , Hyeon-Deuk Kim , Pu Yong-Jin , Kim DaeGwi 
Published: October 2020

AbstractIn quantum dot superlattices, wherein quantum dots are periodically arranged, electronic states between adjacent quantum dots are coupled by quantum resonance, which arises from the short-range electronic coupling of wave functions, and thus the formation of minibands is expected. Quantum dot superlattices have the potential to be key materials for new optoelectronic devices, such as highly efficient solar cells and photodetectors. Herein, we report the fabrication of CdTe quantum dot superlattices via the layer-by-layer assembly of positively charged polyelectrolytes and negatively charged CdTe quantum dots. We can thus control the dimension of the quantum resonance by independently changing the distances between quantum dots in the stacking (out-of-plane) and in-plane directions. Furthermore, we experimentally verify the miniband formation by measuring the excitation energy dependence of the photoluminescence spectra and detection energy dependence of the photoluminescence excitation spectra.
IFI16 promotes human embryonic stem cell trilineage specification through interaction with p53
Authors: He Qian , Wu Zubiao , Yang Wei , Jiang Doukou , Hu Chaofeng , Yang Xiaofei , Li Ning , Li Furong 
Published: October 2020

AbstractTranscriptional regulation plays an essential role in the self-renewal and differentiation of human embryonic stem cells (hESCs). However, how external signals disrupt the self-renewal regulatory network and further drive hESC differentiation remains largely unknown. Here, we found the immune regulative protein, gamma-interferon-inducible protein 16 (IFI16) was involved in the regulation of both self-renewal and differentiation gene expression during hESC trilineage specification through interaction with p53. IFI16 expression levels were upregulated through JNK activation. IFI16 knockdown delayed the downregulation of self-renewal gene expression and suppressed the upregulation of differentiation gene expression, while IFI16 overexpression accelerated trilineage specification. Furthermore, IFI16 stabilized p53-binding in the genome through IFI16-p53 interaction and differentially regulated self-renewal and differentiation gene expression. Together, our results suggest a particular role of IFI16 in differential gene expression regulation during trilineage specification of hESCs in a manner that is dependent on the genome-wide profile of p53-binding directed by IFI16-p53 interaction.
A real-time survey on the psychological impact of mild lockdown for COVID-19 in the Japanese population
Authors: Sugaya Nagisa , Yamamoto Tetsuya , Suzuki Naho , Uchiumi Chigusa 
Published: October 2020

AbstractTo deter the spread of the coronavirus disease 2019 (COVID-19), many countries have imposed a lockdown with restrictions. On 7 April 2020, the Japanese government declared a state of emergency over the COVID-19 outbreak. Japan was in “mild lockdown” which was not enforceable and non-punitive with the declaration. We conducted an online survey to investigate factors associated with psychological distress in the “mild lockdown” under a declared state of emergency for COVID-19. We collected data on 11,333 inhabitants (52.4% women, 46.3 ± 14.6 years) living in the seven prefectures where the declaration was first applied. The investigation dates of this study, 11 and 12 May 2020, were in the final phase of the state of emergency. The survey was conducted in real-time to minimize participants’ recall bias. In addition to psychological inventories often used worldwide, the questionnaires used in this survey included lifestyle and stress management items related to COVID-19 and various socio-demographic items including occupation (e.g. healthcare worker) or income.
The E3 ubiquitin ligase UBR5 interacts with TTC7A and may be associated with very early onset inflammatory bowel disease
Authors: Dhingani Neel , Guo Conghui , Pan Jie , Li Qi , Warner Neil , Jardine Sasha , Leung Gabriella , Kotlarz Daniel , Gonzaga-Jauregui Claudia , Klein Christoph , Snapper Scott B. , Navas-López Víctor Manuel , Muise Aleixo M. 
Published: October 2020

AbstractVery early onset inflammatory bowel disease (VEOIBD) denotes children with onset of IBD before six years of age. A number of monogenic disorders are associated with VEOIBD including tetratricopeptide repeat domain 7A (TTC7A) deficiency. TTC7A-deficiency is characterized by apoptotic colitis in milder cases with severe intestinal atresia and immunodeficiency in cases with complete loss of protein. We used whole exome sequencing in a VEOIBD patient presenting with colitis characterized by colonic apoptosis and no identified known VEOIBD variants, to identify compound heterozygous deleterious variants in the Ubiquitin protein ligase E3 component N-recognin 5 (UBR5) gene. Functional studies demonstrated that UBR5 co-immunoprecipitates with the TTC7A and the UBR5 variants had reduced interaction between UBR5 and TTC7A. Together this implicates UBR5 in regulating TTC7A signaling in VEOIBD patients with apoptotic colitis.
Psychometric properties and concurrent validity of the Transgender Congruence Scale (TCS) in the Swedish setting
Authors: Iliadis Stavros I. , Axfors Cathrine , Friberg Agnes , Arinell Hans , Beckman Ulrika , Fazekas Attila , Frisen Louise , Sandström Lotta , Thelin Nils , Wahlberg Jeanette , Södersten Maria , Papadopoulos Fotios C. 
Published: October 2020

AbstractThe Transgender Congruence Scale (TCS) is a non-binary tool used in Sweden for gender dysphoria (GD) assessment; however, its Swedish version has not been validated. To investigate the psychometric properties of the TCS, its capacity to distinguish individuals with GD and its concurrent validity compared to other scales. Patients with GD (n = 135) and controls (n = 443) filled in a questionnaire containing sociodemographic questions, the TCS, the Utrecht Gender Dysphoria Scale (UGDS), and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). TCS had good discriminatory validity and internal consistency. Patients with GD, stratified by birth-assigned sex, had lower TCS scores compared to controls. Confirmatory factor analysis (CFA) supported the two-factor model of the TCS. Multiple-group CFA suggested measurement invariance between birth-assigned sexes and configural invariance between patients with GD and controls. Area under the ROC curve for birth-assigned males was 0.991 and for females 0.994. A TCS mean value of three provided sensitivity 94.3% and 95.1% as well as specificity 98.6% and 98% for aM and aF, respectively. The TCS was significantly correlated to UGDS and GIDYQ-AA. The TCS may be a valuable tool in the clinical assessment of individuals with GD.
Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer’s disease progression
Authors: Noguchi-Shinohara Moeko , Ono Kenjiro , Hamaguchi Tsuyoshi , Nagai Toshitada , Kobayashi Shoko , Komatsu Junji , Samuraki-Yokohama Miharu , Iwasa Kazuo , Yokoyama Kunihiko , Nakamura Hiroyuki , Yamada Masahito 
Published: October 2020

AbstractWe conducted a randomized placebo-controlled double-blind 24-week trial using Melissa officinalis (M. officinalis) extract richly containing rosmarinic acid (RA) on patients with mild dementia due to Alzheimer’s disease (AD) with the aim to examine the safety and tolerability (primary endpoint) of RA (500 mg daily) and its clinical effects and disease-related biomarker changes (secondary endpoints). Patients (n = 23) diagnosed with mild dementia due to probable AD were randomized to either the placebo or M. officinalis extract group. No differences in vital signs or physical and neurologic examination results were detected between the M. officinalis and placebo groups. No serious adverse events occurred. There were no significant differences in cognitive measures; however, the mean Neuropsychiatric Inventory Questionnaire (NPI-Q) score improved by 0.5 points in the M. officinalis group and worsened by 0.7 points in the placebo group between the baseline and 24-week visit, indicating a significant difference (P = 0.012). No significant differences were apparent in disease-related biomarkers between the groups. M. officinalis extract containing 500 mg of RA taken daily was safe and well-tolerated by patients with mild dementia due to AD. Our results suggest that RA may help prevent the worsening of AD-related neuropsychiatric symptoms.Trial registration: The registration number for this clinical trial is UMIN000007734 (16/04/2012).
Optimal scanning concentration of MR imaging for tumor-bearing nude mice with SPIO-shRNA molecular probe
Authors: Zhang Liqiang , Yang Xinyi , Wen Ming 
Published: October 2020

AbstractThe objective of this study is to investigate the signal changes and optimal scanning concentration of MRI in tumor tissues of tumor-bearing nude mice by SPIO-shRNA molecular probes. 30 BALB/c tumor-bearing nude mice were randomly divided into 5 groups with 6 mice in each group. At the given scanning time (before and 27 h after injection), the caudal vein was respectively injected with iron content of 6 mg·kg−1, 12 mg·kg−1, 18 mg·kg−1, 24 mg·kg−1, and 30 mg·kg−1, and MR examination was simultaneously performed to measure signal intensity changes of tumor tissue and contralateral muscle tissue in each concentration group. After each examination above, the nude mice were sacrificed immediately, and the tumor and muscle tissues were removed for HE and Prussian blue staining,and observed under light microscope. Nude mice in 6 mg, 12 mg and 18 mg groups all survived after probe injection, but some nude mice died in 24 mg and 30 mg groups after probe injection or during scanning. The signal changes of T2WI and T2*WI sequences were the most obvious in MR scanning sequences. Compared with other groups, the signal intensity of the tumor tissue in 18 mg, 24 mg and 30 mg groups were most obvious (P < 0.05), while the 18 mg, 24 mg and 30 mg groups reached no statistical difference (P > 0.05 ); HE staining indicated that structural disorder of tumor tissue as well as increase of nuclear atypia. Prussian Blue staining showed that blue-stained iron particles were present in each experimental group,and the most densely distributed were in 18 mg,24 mg and 30 mg groups. Tumor tissue could be well labeled with SPIO-shRNA molecular probes, and the optimal MR scanning concentration (iron content) is 18 mg·kg−1.
Urban and air pollution: a multi-city study of long-term effects of urban landscape patterns on air quality trends
Authors: Liang Lu , Gong Peng 
Published: October 2020

AbstractMost air pollution research has focused on assessing the urban landscape effects of pollutants in megacities, little is known about their associations in small- to mid-sized cities. Considering that the biggest urban growth is projected to occur in these smaller-scale cities, this empirical study identifies the key urban form determinants of decadal-long fine particulate matter (PM2.5) trends in all 626 Chinese cities at the county level and above. As the first study of its kind, this study comprehensively examines the urban form effects on air quality in cities of different population sizes, at different development levels, and in different spatial-autocorrelation positions. Results demonstrate that the urban form evolution has long-term effects on PM2.5 level, but the dominant factors shift over the urbanization stages: area metrics play a role in PM2.5 trends of small-sized cities at the early urban development stage, whereas aggregation metrics determine such trends mostly in mid-sized cities. For large cities exhibiting a higher degree of urbanization, the spatial connectedness of urban patches is positively associated with long-term PM2.5 level increases. We suggest that, depending on the city’s developmental stage, different aspects of the urban form should be emphasized to achieve long-term clean air goals.
Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome
Authors: Wang Haiqiong , Guo Yongbo , Dong Zhenkun , Li Tao , Xie Xinsheng , Wan Dingming , Jiang Zhongxing , Yu Jifeng , Guo Rong 
Published: October 2020

AbstractTo investigate the U2AF1 gene mutation site, mutation load and co-mutations genes in patients with myelodysplastic syndrome (MDS) and their effects on prognosis. Gene mutation detection by next-generation sequence and related clinical data of 234 MDS patients were retrospectively collected and analyzed for the relationship between the clinical characteristics, treatment efficacy and prognosis of U2AF1 gene mutation. Among the 234 MDS patients, the U2AF1 gene mutation rate was 21.7% (51 cases), and the median variant allele frequency was 39.5%. Compared with the wild type, the U2AF1 mutant had a higher incidence of chromosome 8 aberration, and was positively correlated with the occurrence of ASXL1, RUNX1, SETBP1 gene mutation, negatively correlated with SF3B1, NPM1 genes mutation (p < 0.05). The most common mutation site of U2AF1 was S34F (32 cases), while U2AF1 Q157P site mutations had a higher incidence of chromosome 7 abnormalities (p = 0.003). The U2AF1 gene mutation more frequently coincided with signal pathway related gene mutations (p = 0.043) with a trend of shortened overall survival. Among patients with U2AF1 gene mutations, those with ASXL1 mutations were prone to develop into acute myeloid leukemia, those with RUNX1 mutations had an increased risk of relapse, and those with TET2 mutations had higher 1-year survival rate. Compared with the patient group of lower mutation load (VAF ≤ 40%), the group with higher mutation load of U2AF1 (VAF > 40%) had a significantly lower 1-year survival rate (46.1% and 80.5%, p = 0.027). The criteria of U2AF1 VAF > 40% is an independent indicator for poor prognosis of MDS patients. VAF > 40% of U2AF1 is an independent factor of short OS in MDS patients. MDS patients with a mutation in the Q157P site of U2AF1 and a higher U2AF1 mutation load suggests poor prognosis, and co-mutated genes in U2AF1 can affect disease progression and prognosis.
Generation of a Matrix Gla (Mgp) floxed mouse, followed by conditional knockout, uncovers a new Mgp function in the eye
Authors: Borrás Teresa , Cowley Dale O. , Asokan Priyadarsini , Pandya Kumar 
Published: October 2020

AbstractThe ability to ablate a gene in a given tissue by generating a conditional knockout (cKO) is crucial for determining its function in the targeted tissue. Such tissue-specific ablation is even more critical when the gene’s conventional knockout (KO) is lethal, which precludes studying the consequences of its deletion in other tissues. Therefore, here we describe a successful strategy that generated a Matrix Gla floxed mouse (Mgp.floxed) by the CRISPR/Cas9 system, that subsequently allowed the generation of cKOs by local viral delivery of the Cre-recombinase enzyme. MGP is a well-established inhibitor of calcification gene, highly expressed in arteries’ smooth muscle cells and chondrocytes. MGP is also one of the most abundant genes in the trabecular meshwork, the eye tissue responsible for maintenance of intraocular pressure (IOP) and development of Glaucoma. Our strategy entailed one-step injection of two gRNAs, Cas9 protein and a long-single-stranded-circular DNA donor vector (lsscDNA, 6.7 kb) containing two loxP sites in cis and 900–700 bp 5′/3′ homology arms. Ocular intracameral injection of Mgp.floxed mice with a Cre-adenovirus, led to an Mgp.TMcKO mouse which developed elevated IOP. Our study discovered a new role for the Mgp gene as a keeper of physiological IOP in the eye.