bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atomically dispersed Lewis acid sites boost 2-electron oxygen reduction activity of carbon-based catalysts
Authors: Yang Qihao , Xu Wenwen , Gong Shun , Zheng Guokui , Tian Ziqi , Wen Yujie , Peng Luming , Zhang Linjuan , Lu Zhiyi , Chen Liang 
Published: October 2020

AbstractElucidating the structure-property relationship is crucial for the design of advanced electrocatalysts towards the production of hydrogen peroxide (H2O2). In this work, we theoretically and experimentally discovered that atomically dispersed Lewis acid sites (octahedral M–O species, M = aluminum (Al), gallium (Ga)) regulate the electronic structure of adjacent carbon catalyst sites. Density functional theory calculation predicts that the octahedral M–O with strong Lewis acidity regulates the electronic distribution of the adjacent carbon site and thus optimizes the adsorption and desorption strength of reaction intermediate (*OOH). Experimentally, the optimal catalyst (oxygen-rich carbon with atomically dispersed Al, denoted as O-C(Al)) with the strongest Lewis acidity exhibited excellent onset potential (0.822 and 0.526 V versus reversible hydrogen electrode at 0.1 mA cm−2 H2O2 current in alkaline and neutral media, respectively) and high H2O2 selectivity over a wide voltage range. This study provides a highly efficient and low-cost electrocatalyst for electrochemical H2O2 production.
Towards a reference genome that captures global genetic diversity
Authors: Wong Karen H. Y. , Ma Walfred , Wei Chun-Yu , Yeh Erh-Chan , Lin Wan-Jia , Wang Elin H. F. , Su Jen-Ping , Hsieh Feng-Jen , Kao Hsiao-Jung , Chen Hsiao-Huei , Chow Stephen K. , Young Eleanor , Chu Catherine , Poon Annie , Yang Chi-Fan , Lin Dar-Shong , Hu Yu-Feng , Wu Jer-Yuarn , Lee Ni-Chung , Hwu Wuh-Liang , Boffelli Dario , Martin David , Xiao Ming , Kwok Pui-Yan 
Published: October 2020

AbstractThe current human reference genome is predominantly derived from a single individual and it does not adequately reflect human genetic diversity. Here, we analyze 338 high-quality human assemblies of genetically divergent human populations to identify missing sequences in the human reference genome with breakpoint resolution. We identify 127,727 recurrent non-reference unique insertions spanning 18,048,877 bp, some of which disrupt exons and known regulatory elements. To improve genome annotations, we linearly integrate these sequences into the chromosomal assemblies and construct a Human Diversity Reference. Leveraging this reference, an average of 402,573 previously unmapped reads can be recovered for a given genome sequenced to ~40X coverage. Transcriptomic diversity among these non-reference sequences can also be directly assessed. We successfully map tens of thousands of previously discarded RNA-Seq reads to this reference and identify transcription evidence in 4781 gene loci, underlining the importance of these non-reference sequences in functional genomics. Our extensive datasets are important advances toward a comprehensive reference representation of global human genetic diversity.
Network-based machine learning in colorectal and bladder organoid models predicts anti-cancer drug efficacy in patients
Authors: Kong JungHo , Lee Heetak , Kim Donghyo , Han Seong Kyu , Ha Doyeon , Shin Kunyoo , Kim Sanguk 
Published: October 2020

AbstractCancer patient classification using predictive biomarkers for anti-cancer drug responses is essential for improving therapeutic outcomes. However, current machine-learning-based predictions of drug response often fail to identify robust translational biomarkers from preclinical models. Here, we present a machine-learning framework to identify robust drug biomarkers by taking advantage of network-based analyses using pharmacogenomic data derived from three-dimensional organoid culture models. The biomarkers identified by our approach accurately predict the drug responses of 114 colorectal cancer patients treated with 5-fluorouracil and 77 bladder cancer patients treated with cisplatin. We further confirm our biomarkers using external transcriptomic datasets of drug-sensitive and -resistant isogenic cancer cell lines. Finally, concordance analysis between the transcriptomic biomarkers and independent somatic mutation-based biomarkers further validate our method. This work presents a method to predict cancer patient drug responses using pharmacogenomic data derived from organoid models by combining the application of gene modules and network-based approaches.
Synthesizing AND gate minigene circuits based on CRISPReader for identification of bladder cancer cells
Authors: Liu Yuchen , Huang Weiren , Cai Zhiming 
Published: October 2020

AbstractThe logical AND gate gene circuit based on the CRISPR-Cas9 system can distinguish bladder cancer cells from normal bladder epithelial cells. However, the layered artificial gene circuits have the problems of high complexity, difficulty in accurately predicting the behavior, and excessive redundancy, which cannot be applied to clinical translation. Here, we construct minigene circuits based on the CRISPReader, a technology used to control promoter-less gene expression in a robust manner. The minigene circuits significantly induce robust gene expression output in bladder cancer cells, but have nearly undetectable gene expression in normal bladder epithelial cells. The minigene circuits show a higher capability for cancer identification and intervention when compared with traditional gene circuits, and could be used for in vivo cancer gene therapy using the all-in-one AAV vector. This approach expands the design ideas and concepts of gene circuits in medical synthetic biology.
Conformational disorder of organic cations tunes the charge carrier mobility in two-dimensional organic-inorganic perovskites
Authors: Li Chuanzhao , Yang Jin , Su Fuhai , Tan Junjun , Luo Yi , Ye Shuji 
Published: October 2020

AbstractThe chemical nature of the organic cations governs the optoelectronic properties of two-dimensional organic-inorganic perovskites. But its mechanism is not fully understood. Here, we apply femtosecond broadband sum frequency generation vibrational spectroscopy to investigate the molecular conformation of spacer organic cations in two-dimensional organic-inorganic perovskite films and establish a correlation among the conformation of the organic cations, the charge carrier mobility, and broadband emission. Our study indicates that both the mobility and broadband emission show strong dependence on the molecular conformational order of organic cations. The gauche defect and local chain distortion of organic cations are the structural origin of the in-plane mobility reduction and broad emission in two-dimensional organic-inorganic perovskites. Both of the interlayer distance and the conformational order of the organic cations affect the out-of-plane mobility. This work provides molecular-level understanding of the conformation of organic cations in optimizing the optoelectronic properties of two-dimensional organic-inorganic perovskites.
Genomic surveillance of COVID-19 cases in Beijing
Authors: Du Pengcheng , Ding Nan , Li Jiarui , Zhang Fujie , Wang Qi , Chen Zhihai , Song Chuan , Han Kai , Xie Wen , Liu Jingyuan , Wang Linghang , Wei Lirong , Ma Shanfang , Hua Mingxi , Yu Fengting , Wang Lin , Wang Wei , An Kang , Chen Jianjun , Liu Haizhou , Gao Guiju , Wang Sa , Huang Yanyi , Wu Angela R. , Wang Jianbin , Liu Di , Zeng Hui , Chen Chen 
Published: October 2020

AbstractThe spread of SARS-CoV-2 in Beijing before May, 2020 resulted from transmission following both domestic and global importation of cases. Here we present genomic surveillance data on 102 imported cases, which account for 17.2% of the total cases in Beijing. Our data suggest that all of the cases in Beijing can be broadly classified into one of three groups: Wuhan exposure, local transmission and overseas imports. We classify all sequenced genomes into seven clusters based on representative high-frequency single nucleotide polymorphisms (SNPs). Genomic comparisons reveal higher genomic diversity in the imported group compared to both the Wuhan exposure and local transmission groups, indicating continuous genomic evolution during global transmission. The imported group show region-specific SNPs, while the intra-host single nucleotide variations present as random features, and show no significant differences among groups. Epidemiological data suggest that detection of cases at immigration with mandatory quarantine may be an effective way to prevent recurring outbreaks triggered by imported cases. Notably, we also identify a set of novel indels. Our data imply that SARS-CoV-2 genomes may have high mutational tolerance.
A medicare-based comparative mortality analysis of active surveillance in older women with DCIS
Authors: Akushevich Igor , Yashkin Arseniy P. , Greenup Rachel A. , Hwang E. Shelley 
Published: October 2020

AbstractOver 97% of individuals diagnosed with ductal carcinoma in situ (DCIS) will choose to receive guideline concordant care (GCC), which was originally designed to treat invasive cancers and is associated with treatment related morbidity. An alternative to GCC is active surveillance (AS) where therapy is delayed until medically necessary. Differences in mortality risk between the two approaches in women age 65+ are analyzed in this study. SEER and Medicare information on treatment during the first year after diagnosis was used to identify three cohorts based on treatment type and timing: GCC (N = 21,772; immediate consent for treatment), AS1 (N = 431; delayed treatment within 365 days), and AS2 (N = 205; no treatment/ongoing AS). A propensity score-based approach provided pseudorandomization between GCC and AS groups and survival was then compared. Strong influence of comorbidities on the treatment received was observed for all age-groups, with the greatest burden observed in the AS2 group. All-cause and breast-cancer-specific mortality hazard ratios (HR) for AS1 were not statistically different from the GCC group; AS2 was associated with notably higher risk for both all-cause (HR:3.54; CI:3.29, 3.82) and breast-cancer-specific (HR:10.73; CI:8.63,13.35) mortality. Cumulative mortality was substantially higher from other causes than from breast cancer, regardless of treatment group. Women managed with AS for DCIS had higher all-cause and breast-cancer-specific mortality. This effect declined after accounting for baseline comorbidities. Delays of up to 12 months in initiation of GCC did not underperform immediate surgery.
Prevalence and types of inconsistencies in clinical pharmacogenetic recommendations among major U.S. sources
Authors: Shugg Tyler , Pasternak Amy L. , London Bianca , Luzum Jasmine A. 
Published: October 2020

AbstractClinical implementation of pharmacogenomics (PGx) is slow. Previous studies have identified some inconsistencies among clinical PGx recommendations, but the prevalence and types of inconsistencies have not been comprehensively analyzed among major PGx guidance sources in the U.S. PGx recommendations from the Clinical Pharmacogenetics Implementation Consortium, U.S. Food and Drug Administration drug labels, and major U.S. professional medical organizations were analyzed through May 24, 2019. Inconsistencies were analyzed within the following elements: recommendation category; whether routine screening was recommended; and the specific biomarkers, variants, and patient groups involved. We identified 606 total clinical PGx recommendations, which contained 267 unique drugs. Composite inconsistencies occurred in 48.1% of clinical PGx recommendations overall, and in 93.3% of recommendations from three sources. Inconsistencies occurred in the recommendation category (29.8%), the patient group (35.4%), and routine screening (15.2%). In conclusion, almost one-half of clinical PGx recommendations from prominent U.S. guidance sources contain inconsistencies, which can potentially slow clinical implementation.
Contribution of sex on the underlying mechanism of the gambling disorder severity
Authors: Jiménez-Murcia Susana , Granero Roser , Giménez Mónica , del Pino-Gutiérrez Amparo , Mestre-Bach Gemma , Mena-Moreno Teresa , Moragas Laura , Baño Marta , Sánchez-González Jéssica , de Gracia Marta , Baenas-Soto Isabel , Contaldo S. Fabrizio , Valenciano-Mendoza Eduardo , Mora-Maltas Bernat , López-González Hibai , Menchón José M. , Fernández-Aranda Fernando 
Published: October 2020

AbstractSignificant increasing prevalences have been observed in gambling disorder (GD) in the last decades. This study analyzed the underlying mechanisms of the gambling severity with path analysis (implemented through Structural Equation Modeling, SEM), and assessed the potential moderator effect of the patients’ sex. A sample of n = 512 treatment-seeking patients was assessed for sociodemographics and clinical state previously to the treatment. Results obtained in two separate SEM (for men and women) revealed differences in the direct effects and the mediational links. Among the male subsample, higher GD severity was directly related to the higher cognitive bias and the younger age of onset of the problematic gambling, while impulsivity levels and age of onset achieved an indirect effect on the disordered gambling mediated by the cognitive bias. Among females, GD severity was directly increased by younger age of onset, higher cognitive bias and lower self-directedness, while lower socioeconomic positions, and higher levels in harm avoidance achieved an indirect effect on the gambling severity mediated also by the distortions related to the gambling activity. These results provide new empirical evidence for a better understanding of the GD etiology, suggesting that the underlying complex links mediating the GD severity are strongly related to the patients’ sex. The results can also contribute to design more effectiveness and precise therapy programs of patient-centered care.
Visual word form processing deficits driven by severity of reading impairments in children with developmental dyslexia
Authors: Brem S. , Maurer U. , Kronbichler M. , Schurz M. , Richlan F. , Blau V. , Reithler J. , van der Mark S. , Schulz E. , Bucher K. , Moll K. , Landerl K. , Martin E. , Goebel R. , Schulte-Körne G. , Blomert L. , Wimmer H. , Brandeis D. 
Published: October 2020

AbstractThe visual word form area (VWFA) in the left ventral occipito-temporal (vOT) cortex is key to fluent reading in children and adults. Diminished VWFA activation during print processing tasks is a common finding in subjects with severe reading problems. Here, we report fMRI data from a multicentre study with 140 children in primary school (7.9–12.2 years; 55 children with dyslexia, 73 typical readers, 12 intermediate readers). All performed a semantic task on visually presented words and a matched control task on symbol strings. With this large group of children, including the entire spectrum from severely impaired to highly fluent readers, we aimed to clarify the association of reading fluency and left vOT activation during visual word processing. The results of this study confirm reduced word-sensitive activation within the left vOT in children with dyslexia. Interestingly, the association of reading skills and left vOT activation was especially strong and spatially extended in children with dyslexia. Thus, deficits in basic visual word form processing increase with the severity of reading disability but seem only weakly associated with fluency within the typical reading range suggesting a linear dependence of reading scores with VFWA activation only in the poorest readers.
Decrease in social cohesion in a colonial seabird under a perturbation regime
Authors: Genovart M. , Gimenez O. , Bertolero A. , Choquet R. , Oro D. , Pradel R. 
Published: October 2020

AbstractSocial interactions, through influence on behavioural processes, can play an important role in populations’ resilience (i.e. ability to cope with perturbations). However little is known about the effects of perturbations on the strength of social cohesion in wild populations. Long-term associations between individuals may reflect the existence of social cohesion for seizing the evolutionary advantages of social living. We explore the existence of social cohesion and its dynamics under perturbations by analysing long-term social associations, in a colonial seabird, the Audouin’s gull Larus audouinii, living in a site experiencing a shift to a perturbed regime. Our goals were namely (1) to uncover the occurrence of long-term social ties (i.e. associations) between individuals and (2) to examine whether the perturbation regime affected this form of social cohesion. We analysed a dataset of more than 3500 individuals from 25 years of monitoring by means of contingency tables and within the Social Network Analysis framework. We showed that associations between individuals are not only due to philopatry or random gregariousness but that there are social ties between individuals over the years. Furthermore, social cohesion decreased under the perturbation regime. We sustain that perturbations may lead not only to changes in individuals’ behaviour and fitness but also to a change in populations’ social cohesion. The consequences of decreasing social cohesion are still not well understood, but they can be critical for the population dynamics of social species.
HIV- and HCV-specific markers and echocardiographic pulmonary artery systolic pressure among United States veterans
Authors: Zola Courtney E. , Duncan Meredith S. , So-Armah Kaku , Crothers Kristina A. , Butt Adeel A. , Gibert Cynthia L. , Kim Joon Woo W. , Lim Joseph K. , Re Vincent Lo , Tindle Hilary A. , Freiberg Matthew S. , Brittain Evan L. 
Published: October 2020

AbstractHepatitis C virus (HCV) may increase pulmonary hypertension (PH) risk among people living with HIV (PLWH). Prior studies on this topic have been relatively small and examined selected populations. We determine whether HIV/HCV coinfection is associated with higher pulmonary artery systolic pressure (PASP) and prevalent echocardiographic PH. We performed a cross-sectional analysis of 6032 (16% HIV/HCV coinfected) Veterans Aging Cohort Study participants enrolled 4/1/2003–9/30/2012 with echocardiographic PASP measures. We performed multiple linear and logistic regression analyses to determine whether HIV/HCV mono- or co-infection were associated with PASP and PH compared to uninfected individuals. Individuals with HIV/HCV coinfection displayed a higher PASP than uninfected individuals ($$\widehat{\beta }$$

β
^

=1.10, 95% CI 0.01, 2.20) but there was no association between HIV/HCV coinfection and prevalent PH. Subset analyses examined HIV and HCV disease severity markers separately and jointly. Among PLWH, HCV coinfection ($$\widehat{\beta }$$

β
^

=1.47, 95% CI 0.26, 2.67) and CD4 + cell count ($$\widehat{\beta }$$

β
^

= − 0.68, 95% CI − 1.10, − 0.27), but not HIV viral load nor ART regimen, were associated with PASP. Among people with HCV, neither HIV coinfection nor HCV biomarkers were associated with PASP. Among US veterans referred for echocardiography, HIV/HCV coinfection was not associated with a clinically significant elevation in pulmonary pressure. Lower absolute CD4 + T-cell count was inversely associated with PASP which warrants further investigation in prospective studies.
The HIF1α/JMY pathway promotes glioblastoma stem-like cell invasiveness after irradiation
Authors: Gauthier Laurent R. , Saati Mahasen , Bensalah-Pigeon Hayet , Ben M’Barek Karim , Gitton-Quent Oscar , Bertrand Romane , Busso Didier , Mouthon Marc-André , Collura Ada , Junier Marie-Pierre , Chneiweiss Hervé , Pineda José R. , Boussin François D. 
Published: October 2020

AbstractHuman glioblastoma (GBM) is the most common primary malignant brain tumor. A minor subpopulation of cancer cells, known as glioma stem-like cells (GSCs), are thought to play a major role in tumor relapse due to their stem cell-like properties, their high resistance to conventional treatments and their high invasion capacity. We show that ionizing radiation specifically enhances the motility and invasiveness of human GSCs through the stabilization and nuclear accumulation of the hypoxia-inducible factor 1α (HIF1α), which in turn transcriptionally activates the Junction-mediating and regulatory protein (JMY). Finally, JMY accumulates in the cytoplasm where it stimulates GSC migration via its actin nucleation-promoting activity. Targeting JMY could thus open the way to the development of new therapeutic strategies to improve the efficacy of radiotherapy and prevent glioma recurrence.
Stress-sensing in the human greying hair follicle: Ataxia Telangiectasia Mutated (ATM) depletion in hair bulb melanocytes in canities-prone scalp
Authors: Sikkink Stephen K. , Mine Solene , Freis Olga , Danoux Louis , Tobin Desmond J. 
Published: October 2020

AbstractCanities (or hair greying) is an age-linked loss of the natural pigment called melanin from hair. While the specific cause(s) underlying the loss of melanogenically-active melanocytes from the anagen hair bulbs of affected human scalp remains unclear, oxidative stress sensing appears to be a key factor involved. In this study, we examined the follicular melanin unit in variably pigmented follicles from the aging human scalp of healthy individuals (22–70 years). Over 20 markers were selected within the following categories: melanocyte-specific, apoptosis, cell cycle, DNA repair/damage, senescence and oxidative stress. As expected, a reduction in melanocyte-specific markers in proportion to the extent of canities was observed. A major finding of our study was the intense and highly specific nuclear expression of Ataxia Telangiectasia Mutated (ATM) protein within melanocytes in anagen hair follicle bulbs. ATM is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks and functions as an important sensor of reactive oxygen species (ROS) in human cells. The incidence and expression level of ATM correlated with pigmentary status in canities-affected hair follicles. Moreover, increased staining of the redox-associated markers 8-OHdG, GADD45 and GP-1 were also detected within isolated bulbar melanocytes, although this change was not clearly associated with donor age or canities extent. Surprisingly, we were unable to detect any specific change in the expression of other markers of oxidative stress, senescence or DNA damage/repair in the canities-affected melanocytes compared to surrounding bulbar keratinocytes. By contrast, several markers showed distinct expression of markers for oxidative stress and apoptosis/differentiation in the inner root sheath (IRS) as well as other parts of the hair follicle. Using our in vitro model of primary human scalp hair follicle melanocytes, we showed that ATM expression increased after incubation with the pro-oxidant hydrogen peroxide (H2O2). In addition, this ATM increase was prevented by pre-incubation of cells with antioxidants. The relationship between ATM and redox stress sensing was further evidenced as we observed that the inhibition of ATM expression by chemical inhibition promoted the loss of melanocyte viability induced by oxidative stress. Taken together these new findings illustrate the key role of ATM in the protection of human hair follicle melanocytes from oxidative stress/damage within the human scalp hair bulb. In conclusion, these results highlight the remarkable complexity and role of redox sensing in the status of human hair follicle growth, differentiation and pigmentation.