bluuebunny/crossref_metadata_2025_split huggingface dataset:
Looking at the BiG picture: incorporating bipartite graphs in drug response prediction
Authors: Hostallero David Earl , Li Yihui , Emad Amin 
Published: June 2022

AbstractMotivationThe increasing number of publicly available databases containing drugs’ chemical structures, their response in cell lines, and molecular profiles of the cell lines has garnered attention to the problem of drug response prediction. However, many existing methods do not fully leverage the information that is shared among cell lines and drugs with similar structure. As such, drug similarities in terms of cell line responses and chemical structures could prove to be useful in forming drug representations to improve drug response prediction accuracy.ResultsWe present two deep learning approaches, BiG-DRP and BiG-DRP+, for drug response prediction. Our models take advantage of the drugs’ chemical structure and the underlying relationships of drugs and cell lines through a bipartite graph and a heterogeneous graph convolutional network that incorporate sensitive and resistant cell line information in forming drug representations. Evaluation of our methods and other state-of-the-art models in different scenarios shows that incorporating this bipartite graph significantly improves the prediction performance. In addition, genes that contribute significantly to the performance of our models also point to important biological processes and signaling pathways. Analysis of predicted drug response of patients’ tumors using our model revealed important associations between mutations and drug sensitivity, illustrating the utility of our model in pharmacogenomics studies.Availability and implementationAn implementation of the algorithms in Python is provided in https://github.com/ddhostallero/BiG-DRP.Supplementary informationSupplementary data are available at Bioinformatics online.
A polymorphic variant in telomere maintenance is associated with worrisome features and high-risk stigmata development in IPMNs
Authors: Giaccherini Matteo , Gentiluomo Manuel , Arcidiacono Paolo Giorgio , Falconi Massimo , Testoni Sabrina Gloria Giulia , Apadula Laura , Lauri Gaetano , Di Franco Gregorio , Fatucchi Lorenzo Maria , Petrone Maria Chiara , Corradi Chiara , Crippa Stefano , Morelli Luca , Capurso Gabriele , Campa Daniele 
Published: June 2022

Abstract
Intraductal papillary mucinous neoplasms (IPMNs) are nonobligatory precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The identification of molecular biomarkers able to predict the risk of progression of IPMNs toward malignancy is largely lacking and sorely needed. Telomere length (TL) is associated with the susceptibility of developing cancers, including PDAC. Moreover, several PDAC risk factors have been shown to be associated with IPMN transition to malignancy. TL is genetically determined, and the aim of this study was to use 11 SNPs, alone or combined in a score (teloscore), to estimate the causal relation between genetically determined TL and IPMNs progression. For this purpose, 173 IPMN patients under surveillance were investigated. The teloscore did not show any correlation, however, we observed an association between PXK-rs6772228-A and an increased risk of IPMN transition to malignancy (HR = 3.17; 95%CI 1.47–6.84; P = 3.24 × 10-3). This effect was also observed in a validation cohort of 142 IPMNs even though the association was not statistically significant. The combined analysis was consistent showing an association between PXK-rs6772228-A and increased risk of progression. The A allele of this SNP is strongly associated with shorter LTL that in turn have been reported to be associated with increased risk of developing PDAC. These results clearly highlight the importance of looking for genetic variants as potential biomarkers in this setting in order to further our understanding the etiopathogenesis of PDAC and suggest that genetically determined TL might be an additional marker of IPMN prognosis.
Middle East Respiratory Syndrome Coronavirus Infection Elicits Long-lasting Specific Antibody, T and B Cell Immune Responses in Recovered Individuals
Authors: Alhabbab Rowa Y , Algaissi Abdullah , Mahmoud Ahmed Bakr , Alkayyal Almohanad A , Al-Amri Sawsan , Alfaleh Mohamed A , Basabrain Mohammad , Alsubki Roua Abdullah , Almarshad Ibrahim S , Alhudaithi Abdulelah M , Gafari Omar A Al , Alshamlan Yasser A , Aldossari Hassan M , Alsafi Mohammed M , Bukhari Abdullah , Bajhmom Wael , Memish Ziad A , Al Salem Waleed S , Hashem Anwar M 
Published: June 2022

Abstract

Background
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic zoonotic betacoronavirus and a global public health concern. Better undersetting of the immune responses to MERS-CoV is needed to characterize the correlates of protection and durability of the immunity and to aid in developing preventative and therapeutic interventions. Although MERS-CoV–specific circulating antibodies could persist for several years post-recovery, their waning raises concerns about their durability and role in protection. Nonetheless, memory B and T cells could provide long-lasting protective immunity despite the serum antibodies levels.

Methods
Serological and flow cytometric analysis of MERS-CoV–specific immune responses were performed on samples collected from a cohort of recovered individuals who required intensive care unit (ICU) admission as well as hospital or home isolation several years after infection to characterize the longevity and quality of humoral and cellular immune responses.

Results
Our data showed that MERS-CoV infection could elicit robust long-lasting virus-specific binding and neutralizing antibodies as well as T- and B-cell responses up to 6.9 years postinfection regardless of disease severity or need for ICU admission. Apart from the persistent high antibody titers, this response was characterized by B-cell subsets with antibody-independent functions as demonstrated by their ability to produce tumor necrosis factor α (TNF-α), interleukin (IL)-6, and interferon γ (IFN-γ) cytokines in response to antigen stimulation. Furthermore, virus-specific activation of memory CD8+ and CD4+ T cell subsets from MERS-recovered patients resulted in secretion of high levels of TNF-α, IL-17, and IFN-γ.

Conclusions
MERS-CoV infection could elicit robust long-lasting virus-specific humoral and cellular responses.
A new score for life-threatening ventricular arrhythmias and sudden cardiac death in adults with transposition of the great arteries and a systemic right ventricle
Authors: Ladouceur Magalie , Van De Bruaene Alexander , Kauling Robert , Budts Werner , Roos-Hesselink Jolien , Albert Sandra Villagrá , Perez Inmaculada Sanchez , Sarubbi Berardo , Fusco Flavia , Gallego Pastora , Rodriguez-Puras Maria Jose , Bouchardy Judith , Blanche Coralie , Rutz Tobias , Prokselj Katja , Labombarda Fabien , Iserin Laurence , Wong Tom , Gatzoulis Michael A 
Published: June 2022

Abstract

Aims
To investigate the incidence of major adverse ventricular arrhythmias and related events (MAREs) and to develop a stratification tool predicting MAREs in adults with a systemic right ventricle (sRV).

Methods and results
In a multicentre approach, all adults (≥16 years old) with a sRV undergoing follow-up between 2000 and 2018 were identified. The incidence of MAREs, defined as sudden cardiac death, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator (ICD) therapy, was analysed. The association of MAREs with clinical, electrical, and echocardiographic parameters was evaluated. A total of 1184 patients (median age 27.1 years; interquartile range 19.9–34.9 years; 59% male; 70% with atrial switch repair for D-transposition of the great arteries) were included. The incidence of MAREs was 6.3 per 1000 patient-years. On multivariate analysis, age, history of heart failure, syncope, QRS duration, severe sRV dysfunction and at least moderate left ventricular outflow tract obstruction were retained in the final model with a C-index of 0.78 [95% confidence interval (CI) 0.72–0.83] and a calibration slope of 0.93 (95% CI 0.64–1.21). For every five ICDs implanted in patients with a 5-year MARE risk &gt;10%, one patient may potentially be spared from a MARE.

Conclusion
Sudden cardiac death remains a devastating cause of death in a contemporary adult cohort with a sRV. A prediction model based on clinical, electrocardiographic, and echocardiographic parameters was devised to estimate MARE risk and to identify high-risk patients who may benefit from primary prevention ICD implantation.
Understanding a defensive response of methicillin-resistant Staphylococcus aureus after exposure to multiple cycles of sub-lethal blue light
Authors: Luo Shuanghua , Yang Xi , Wu Shuyan , Li Yuanbu , Wu Jiaxin , Liu Minmin , Liu Zhaojun , Yu Keyang , Wang Xiaoyuan , Dai Tianhong , Huang Xiaodong , Hu Xiaoqing 
Published: June 2022

Abstract
Blue light (BL) has shown bactericidal effectiveness against methicillin-resistant Staphylococcus aureus (MRSA), one of the major clinical pathogens with antibiotic resistance. Bacteria likely respond to the oxidative stress induced by BL; however, the defensive response is still unclear. This study aimed to reveal the phenotypic change in MRSA after being exposed to 15 cycles of sub-lethal BL illumination. The comparative transcriptomic results showed that the expression of peptidoglycan (PG) synthesis gene glmS was significantly upregulated in the cells after the multiple cycle light treatment, and the biochemical analysis determined that the content of PG synthesized was increased by 25.86% when compared with that in control cells. Furthermore, significant thickening of the cell wall was observed under a transmission electron microscope (P &lt; .05). The light sensitivity of the tested MRSA strain was reduced after the multiple cycle light treatment, indicating the possibility of MRSA being more adaptive to the BL stress. The present study suggested that multiple cycles of sub-lethal BL could change the light susceptibility of MRSA through thickening the cell wall.
On Purpose: Interest, Disinterest and Literature We Can Live By
Authors: Hutchinson Ben 
Published: June 2022

Abstract
The idea of ‘literature we can live by’ crystallizes the paradox of art: defined by its distance from life, it requires, at the same time, proximity to life. We turn to art because it offers a protected space of disinterested play – yet we are also profoundly interested in its ethical implications. In the words of Rilke’s ‘Archaic Torso of Apollo’, the work of art – and through its Apollonian patron, literature in particular – tells us that we must change our lives. Ranging widely from antiquity to modernity while highlighting key moments in early modernity and the Enlightenment, this essay identifies a recurring tension between two visions of literature: to be able to comment insightfully on life, it must be apart from it; to be able to respond adequately to life, it must be a part of it. It is not just the metaphors we live by, in other words, but also the metonyms.
A Uniform Sobolev Inequality for Ancient Ricci Flows with Bounded Nash Entropy
Authors: Chan Pak-Yeung , Ma Zilu , Zhang Yongjia 
Published: June 2022

AbstractThis note is a continuation of [7]. We shall show that an ancient Ricci flow with uniformly bounded Nash entropy also has uniformly bounded $\nu $-functional. Consequently, on such an ancient solution, there are uniform logarithmic Sobolev and Sobolev inequalities. We emphasize that the main theorem in this paper is true so long as the theory in [3] is valid, and in particular, when the underlying manifold is closed.
On the Formal Degree Conjecture for Non-Singular Supercuspidal Representations
Authors: Ohara Kazuma 
Published: June 2022

AbstractWe prove the formal degree conjecture for non-singular supercuspidal representations based on Schwein’s work [16] proving the formal degree conjecture for regular supercuspidal representations. The main difference between our work and Schwein’s work is that in non-singular case, the Deligne–Lusztig representations can be reducible, and the $S$-groups are not necessarily abelian. Therefore, we have to compare the dimensions of irreducible constituents of the Deligne–Lusztig representations and the dimensions of irreducible representations of $S$-groups.
The efficacy of trimodal chemoradiotherapy with gemcitabine and cisplatin as a bladder-preserving strategy for the treatment of muscle-invasive bladder cancer: a single-arm phase II study
Authors: Kobayashi Keita , Matsumoto Hiroaki , Misumi Taku , Ito Hideaki , Hirata Hiroshi , Nagao Kazuhiro , Matsuyama Hideyasu 
Published: June 2022

Abstract

Objective
Radical cystectomy remains the standard treatment for muscle-invasive bladder cancer; however, a substantial number of patients with muscle-invasive bladder cancer are not appropriate candidates to radical cystectomy due to co-morbidities or anxiety regarding bladder preservation. Trimodal bladder-sparing therapy is an intelligent and attractive treatment option for such patients. We established a novel treatment strategy using trimodal treatment with gemcitabine and cisplatin.

Methods
Patients diagnosed with muscle-invasive bladder cancer by transurethral resection of bladder tumor and who wished for bladder preservation were recruited. The regimens were gemcitabine 300 mg/m2 and cisplatin 30 mg/m2 in day 1 and concomitant irradiation 1.8 Gy/Fr, five fractions per week. Irradiation was administered to the true pelvis up to 36 Gy and was then boosted to the entire bladder until a total of 54 Gy. Transurethral resection of bladder tumor was also performed after chemoradiotherapy to evaluate pathological response to treatment. We evaluated treatment efficacy and survival, safety of chemoradiotherapy with gemcitabine and cisplatin.

Results
Thirty-eight patients were enrolled, and three patients were excluded. Pathological complete response after chemoradiotherapy was observed in 31 patients, and the 5-year bladder-intact metastasis-free survival rate was 76%. The 5-year cancer-specific and overall survival rates for chemoradiotherapy were 85 and 75%, respectively, which were not significantly different from those for radical cystectomy (73 and 71%, respectively). Grade 3/4 adverse events included neutropenia (63%), anemia (18%) and thrombocytopenia (37%); however, treatment-related deaths were not observed.

Conclusions
Chemoradiotherapy using gemcitabine and cisplatin for muscle-invasive bladder cancer is effective for local cancer control and shows no significant difference in oncological prognosis compared with radical cystectomy.
Cannabis significantly alters DNA methylation of the human ovarian follicle in a concentration-dependent manner
Authors: Fuchs Weizman Noga , Wyse Brandon A , Montbriand Janice , Jahangiri Sahar , Librach Clifford L 
Published: June 2022

AbstractCannabis is increasingly consumed by women of childbearing age, and the reproductive and epigenetic effects are unknown. The purpose of this study was to evaluate the potential epigenetic implications of cannabis use on the female ovarian follicle. Whole-genome methylation was assessed in granulosa cells from 14 matched case-control patients. Exposure status was determined by liquid chromatography–mass spectrometry (LC-MS/MS) measurements of five cannabis-derived phytocannabinoids in follicular fluid. DNA methylation was measured using the Illumina TruSeq Methyl Capture EPIC kit. Differential methylation, pathway analysis and correlation analysis were performed. We identified 3679 differentially methylated sites, with two-thirds affecting coding genes. A hotspot region on chromosome 9 was associated with two genomic features, a zinc-finger protein (ZFP37) and a long non-coding RNA (FAM225B). There were 2214 differentially methylated genomic features, 19 of which have been previously implicated in cannabis-related epigenetic modifications in other organ systems. Pathway analysis revealed enrichment in G protein-coupled receptor signaling, cellular transport, immune response and proliferation. Applying strict criteria, we identified 71 differentially methylated regions, none of which were previously annotated in this context. Finally, correlation analysis revealed 16 unique genomic features affected by cannabis use in a concentration-dependent manner. Of these, the histone methyltransferases SMYD3 and ZFP37 were hypomethylated, possibly implicating histone modifications as well. Herein, we provide the first DNA methylation profile of human granulosa cells exposed to cannabis. With cannabis increasingly legalized worldwide, further investigation into the heritability and functional consequences of these effects is critical for clinical consultation and for legalization guidelines.
Shade triggers posttranscriptional PHYTOCHROME-INTERACTING FACTOR-dependent increases in H3K4 trimethylation
Authors: Calderon Robert H , Dalton Jutta , Zhang Yu , Quail Peter H 
Published: June 2022

Abstract
The phytochrome (phy)-PHYTOCHROME-INTERACTING FACTOR (PIF) sensory module perceives and transduces light signals to direct target genes (DTGs), which then drive the adaptational responses in plant growth and development appropriate to the prevailing environment. These signals include the first exposure of etiolated seedlings to sunlight upon emergence from subterranean darkness and the change in color of the light that is filtered through, or reflected from, neighboring vegetation (“shade”). Previously, we identified three broad categories of rapidly signal-responsive genes: those repressed by light and conversely induced by shade; those repressed by light, but subsequently unresponsive to shade; and those responsive to shade only. Here, we investigate the potential role of epigenetic chromatin modifications in regulating these contrasting patterns of phy-PIF module-induced expression of DTGs in Arabidopsis (Arabidopsis thaliana). Using RNA-seq and ChIP-seq to determine time-resolved profiling of transcript and histone 3 lysine 4 trimethylation (H3K4me3) levels, respectively, we show that, whereas the initial dark-to-light transition triggers a rapid, apparently temporally coincident decline of both parameters, the light-to-shade transition induces similarly rapid increases in transcript levels that precede increases in H3K4me3 levels. Together with other recent findings, these data raise the possibility that, rather than being causal in the shade-induced expression changes, H3K4me3 may function to buffer the rapidly fluctuating shade/light switching that is intrinsic to vegetational canopies under natural sunlight conditions.
Big data from a popular app reveals that fishing creates superhighways for aquatic invaders
Authors: Weir Jessica L , Vacura Kirsten , Bagga Jay , Berland Adam , Hyder Kieran , Skov Christian , Attby Johan , Venturelli Paul A 
Published: June 2022

Abstract
Human activities are the leading cause of biological invasions that cause ecologic and economic damage around the world. Aquatic invasive species (AIS) are often spread by recreational anglers who visit two or more bodies of water within a short time frame. Movement data from anglers are, therefore, critical to predicting, preventing, and monitoring the spread of AIS. However, the lack of broad-scale movement data has restricted efforts to large and popular lakes or small geographic extents. Here, we show that recreational fishing apps are an abundant, convenient, and relatively comprehensive source of “big” movement data across the contiguous United States. Our analyses revealed a dense network of angler movements that was dramatically more interconnected and extensive than the network that is formed naturally by rivers and streams. Short-distanced movements by anglers combined to form invasion superhighways that spanned the contiguous United States. We also identified possible invasion fronts and invaded hub lakes that may be superspreaders for two relatively common aquatic invaders. Our results provide unique insight into the national network through which AIS may be spread, increase opportunities for interjurisdictional coordination that is essential to addressing the problem of AIS, and highlight the important role that anglers can play in providing accurate data and preventing invasions. The advantages of mobile devices as both sources of data and a means of engaging the public in their shared responsibility to prevent invasions are probably general to all forms of tourism and recreation that contribute to the spread of invasive species.
Partners in crime: Tbf1 and Vid22 promote expansions of long human telomeric repeats at an interstitial chromosome position in yeast
Authors: Radchenko Elina A , Aksenova Anna Y , Volkov Kirill V , Shishkin Alexander A , Pavlov Youri I , Mirkin Sergei M 
Published: June 2022

Abstract
In humans, telomeric repeats (TTAGGG)n are known to be present at internal chromosomal sites. These interstitial telomeric sequences (ITSs) are an important source of genomic instability, including repeat length polymorphism, but the molecular mechanisms responsible for this instability remain to be understood. Here, we studied the mechanisms responsible for expansions of human telomeric (Htel) repeats that were artificially inserted inside a yeast chromosome. We found that Htel repeats in an interstitial chromosome position are prone to expansions. The propensity of Htel repeats to expand depends on the presence of a complex of two yeast proteins: Tbf1 and Vid22. These two proteins are physically bound to an interstitial Htel repeat, and together they slow replication fork progression through it. We propose that slow progression of the replication fork through the protein complex formed by the Tbf1 and Vid22 partners at the Htel repeat cause DNA strand slippage, ultimately resulting in repeat expansions.
Vaccinating children against COVID-19 is crucial to protect schools and communities
Authors: Rosenstrom Erik T , Mele Jessica , Ivy Julie S , Mayorga Maria E , Patel Mehul D , Lich Kristen Hassmiller , Delamater Paul L , Smith Raymond L , Swann Julie L 
Published: June 2022

Abstract
To evaluate the joint impact of childhood vaccination rates and school masking policies on community transmission and severe outcomes due to COVID-19, we utilized a stochastic, agent-based simulation of North Carolina to test 24 health policy scenarios. In these scenarios, we varied the childhood (ages 5 to 19) vaccination rate relative to the adult's (ages 20 to 64) vaccination rate and the masking relaxation policies in schools. We measured the overall incidence of disease, COVID-19-related hospitalization, and mortality from 2021 July 1 to 2023 July 1. Our simulation estimates that removing all masks in schools in January 2022 could lead to a 31% to 45%, 23% to 35%, and 13% to 19% increase in cumulative infections for ages 5 to 9, 10 to 19, and the total population, respectively, depending on the childhood vaccination rate. Additionally, achieving a childhood vaccine uptake rate of 50% of adults could lead to a 31% to 39% reduction in peak hospitalizations overall masking scenarios compared with not vaccinating this group. Finally, our simulation estimates that increasing vaccination uptake for the entire eligible population can reduce peak hospitalizations in 2022 by an average of 83% and 87% across all masking scenarios compared to the scenarios where no children are vaccinated. Our simulation suggests that high vaccination uptake among both children and adults is necessary to mitigate the increase in infections from mask removal in schools and workplaces.