bluuebunny/crossref_metadata_2025_split huggingface dataset:
PlantBind: an attention-based multi-label neural network for predicting plant transcription factor binding sites
Authors: Yan Wenkai , Li Zutan , Pian Cong , Wu Yufeng 
Published: September 2022

Abstract
Identification of transcription factor binding sites (TFBSs) is essential to understanding of gene regulation. Designing computational models for accurate prediction of TFBSs is crucial because it is not feasible to experimentally assay all transcription factors (TFs) in all sequenced eukaryotic genomes. Although many methods have been proposed for the identification of TFBSs in humans, methods designed for plants are comparatively underdeveloped. Here, we present PlantBind, a method for integrated prediction and interpretation of TFBSs based on DNA sequences and DNA shape profiles. Built on an attention-based multi-label deep learning framework, PlantBind not only simultaneously predicts the potential binding sites of 315 TFs, but also identifies the motifs bound by transcription factors. During the training process, this model revealed a strong similarity among TF family members with respect to target binding sequences. Trans-species prediction performance using four Zea mays TFs demonstrated the suitability of this model for transfer learning. Overall, this study provides an effective solution for identifying plant TFBSs, which will promote greater understanding of transcriptional regulatory mechanisms in plants.
The fractal brain: scale-invariance in structure and dynamics
Authors: Grosu George F , Hopp Alexander V , Moca Vasile V , Bârzan Harald , Ciuparu Andrei , Ercsey-Ravasz Maria , Winkel Mathias , Linde Helmut , Mureșan Raul C 
Published: September 2022

AbstractThe past 40 years have witnessed extensive research on fractal structure and scale-free dynamics in the brain. Although considerable progress has been made, a comprehensive picture has yet to emerge, and needs further linking to a mechanistic account of brain function. Here, we review these concepts, connecting observations across different levels of organization, from both a structural and functional perspective. We argue that, paradoxically, the level of cortical circuits is the least understood from a structural point of view and perhaps the best studied from a dynamical one. We further link observations about scale-freeness and fractality with evidence that the environment provides constraints that may explain the usefulness of fractal structure and scale-free dynamics in the brain. Moreover, we discuss evidence that behavior exhibits scale-free properties, likely emerging from similarly organized brain dynamics, enabling an organism to thrive in an environment that shares the same organizational principles. Finally, we review the sparse evidence for and try to speculate on the functional consequences of fractality and scale-freeness for brain computation. These properties may endow the brain with computational capabilities that transcend current models of neural computation and could hold the key to unraveling how the brain constructs percepts and generates behavior.
Evaluation of an Opt-Out Protocol for Antibiotic De-Escalation in Patients With Suspected Sepsis: A Multicenter, Randomized, Controlled Trial
Authors: Moehring Rebekah W , Yarrington Michael E , Warren Bobby G , Lokhnygina Yuliya , Atkinson Erica , Bankston Allison , Collucio Julia , David Michael Z , Davis Angelina E , Davis Janice , Dionne Brandon , Dyer April P , Jones Travis M , Klompas Michael , Kubiak David W , Marsalis John , Omorogbe Jacqueline , Orajaka Patricia , Parish Alice , Parker Todd , Pearson Jeffrey C , Pearson Tonya , Sarubbi Christina , Shaw Christian , Spivey Justin , Wolf Robert , Wrenn Rebekah H , Dodds Ashley Elizabeth S , Anderson Deverick J ,   the Centers for Disease Control and Prevention’s Prevention Epicenters Program
Published: September 2022

Abstract

Background
Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis.

Methods
We evaluated non–intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020. A 23-item safety check excluded patients with ongoing signs of systemic infection, concerning or inadequate microbiologic data, or high-risk conditions. Eligible patients were randomized to the opt-out protocol vs usual care. Primary outcome was post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted to encourage antibiotic discontinuation using opt-out language. If continued, clinicians discussed the rationale for continuing antibiotics and de-escalation plans. To evaluate those with zero post-enrollment DOT, hurdle models provided 2 measures: odds ratio of antibiotic continuation and ratio of mean DOT among those who continued antibiotics.

Results
Among 9606 patients screened, 767 (8%) were enrolled. Intervention patients had 32% lower odds of antibiotic continuation (79% vs 84%; odds ratio, 0.68; 95% confidence interval [CI], .47–.98). DOT among those who continued antibiotics were similar (ratio of means, 1.06; 95% CI, .88–1.26). Fewer intervention patients were exposed to extended-spectrum antibiotics (36% vs 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%). Thirty-day safety events were similar.

Conclusions
An antibiotic opt-out protocol that targeted patients with suspected sepsis resulted in more antibiotic discontinuations, similar DOT when antibiotics were continued, and no evidence of harm.

Clinical Trials Registration
NCT03517007.
The role of interleukin-33 in organ fibrosis
Authors: Di Carmine Samuele , Scott Molly M , McLean Mairi H , McSorley Henry J 
Published: September 2022

Summary
Interleukin (IL)-33 is highly expressed in the nucleus of cells present at barrier sites and signals via the ST2 receptor. IL-33 signalling via ST2 is essential for return to tissue homeostasis after acute inflammation, promoting fibrinogenesis and wound healing at injury sites. However, this wound-healing response becomes aberrant during chronic or sustained inflammation, leading to transforming growth factor beta (TGF-β) release, excessive extracellular matrix deposition, and fibrosis. This review addresses the role of the IL-33 pathway in fibrotic diseases of the lung, liver, gastrointestinal tract, skin, kidney and heart. In the lung and liver, IL-33 release leads to the activation of pro-fibrotic TGF-β, and in these sites, IL-33 has clear pro-fibrotic roles. In the gastrointestinal tract, skin, and kidney, the role of IL-33 is more complex, being both pro-fibrotic and tissue protective. Finally, in the heart, IL-33 serves cardioprotective functions by favouring tissue healing and preventing cardiomyocyte death. Altogether, this review indicates the presence of an unclear and delicate balance between resolving and pro-fibrotic capabilities of IL-33, which has a central role in the modulation of type 2 inflammation and fibrosis in response to tissue injury.
333. THE EGIDIUS PROJECT: A NETWORK APPROACH TOWARDS EXCELLENT MULTIDISCIPLINARY QUALITY OF CARE FOR PATIENTS WITH ESOPHAGEAL AND GASTRIC CANCER
Authors: Geerts Julie , Wijnhoven Bas , Rosman Camiel , Verhoeven Rob , Nieuwenhuijzen Grard ,   Egidius Expert Collaborator Group
Published: September 2022

Abstract
Diagnosis and treatment of esophageal and gastric cancer is complex and requires a multidisciplinary network approach involving multiple hospitals in the Netherlands. Recent studies have shown that there is still substantial practice variation and variation in outcomes. The aim of this project is to improve quality of care in oncological networks for patients with esophageal or gastric cancer for every disease stage and to minimize undesirable practice variation and improve outcomes.
To achieve excellent quality of care of all participants in an oncological network, a multidisciplinary improvement process has been initiated involving all participating hospitals. The pilot project has started in three networks comprising 20 hospitals. First, physicians from different specialties (surgery, oncology, radiotherapy and gastro-enterology), patient advocates and health insurance representatives determined the most important quality-of-care indicators to be measured prospectively. Second, Plan-Do-Check-ACT (PDCA) cycles will be established to evaluate process and outcome indicators with both professionals and patients, leading to improvement processes to be initiated. These will be evaluated quarterly.
Specialists and patient representatives have defined a list of quality-of-care indicators for all hospitals within this project: four indicators on gastroenterology, three for radiotherapy, four surgical indicators, six on medical oncology and six on the overarching care pathway. See table 1 for the full list of indicators. The prospective measurements will start May 2022. The first results and PDCA-cycles are expected to take place in June 2022. It is expected to lead to new insights in hospital variation in the Netherlands and to start an improvement process which will be agreed upon in the upcoming discussions.
A unique network multidisciplinary project involving physicians as well as patient and health insurance representatives has been initiated. Novel and existing specialty-specific and general quality-of-care indicators haven been defined. The quarterly evaluations of this specific set of indicators to assess practice performance and variation is expected to lead to new insights, improve outcomes and reduce undesirable practice variation within the Netherlands.
359. INTRATUMORAL MICROBIOME IMPACTS IMMUNE INFILTRATES IN TUMOR MICROENVIRONMENT AND PREDICTS PROGNOSIS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA PATIENTS
Authors: Xie Xuan , Xie Xuan , Zhang Shuishen , Ma Xiaofan , Zhan Jing , Pan Chuqing , Zhang Huizhong , Xie Xiuying , Wen Jing 
Published: September 2022

Abstract
Emerging evidence suggests different intratumoral microbiome exists in different tumors and plays a crucial function in carcinogenesis. However, whether intratumoral microbiome in esophageal squamous cell carcinoma (ESCC) impacts clinical outcomes and its mechanism remains unclear.
16S rDNA amplicon sequencing was performed on surgical resected samples from 106 ESCC patients including 25 paired tumorous and non-tumorous tissues (NTs) to analyze intratumoral microbiome abundance and its composition. Multiplex fluorescent immunohistochemistry (mfIHC) staining was used to profile the phenotypes of immune infiltrates in tumor microenvironment (TME).
Both Shannon index and operational taxonomic units (OTUs), representing alpha-diversity of microbiome, were found significantly lower in tumors comparing to the corresponding NTs. Multivariate analysis revealed that the intratumoral Shannon index, the relative abundance of Lactobacillus and the pTNM stage were independently associated with patients’ overall survival. Furthermore, the relative abundance of Lactobacillus and Shannon index were both positively correlated with the proportions of PD-L1+ epithelial cells (ECs) and tumor-associated macrophages (TAMs, and Shannon index was negatively correlated with the proportions of natural killer cells (NKs) and activated cytotoxic T cells (aCTLs) in TME, indicating an immunosuppressive microenvironment.
These findings underscored for the first time that the high abundance of intratumoral Lactobacillus and microbiome alpha-diversity were associated with poor long-term survival of ESCC patients, which might be achieved by increasing PD-L1 + ECs and PD-L1 + TAMs and decreasing aCTLs and NKs in TME.
362. CLINICAL VALUE AND EFFICACY INDEX OF LYMPHADENECTOMY FOR THORACIC ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Li Kexun , Leng Xue Feng , Du Kunyi , Liu Kun , He Wenwu , Wang Qifeng , Luo Xi , Wang Chenghao , Wang Kangning , Liu Guangyuan , Wei Xing , Li Haojun , Zhou Qiang , Li Zhiyu , Zheng Kai , Li Changding , Li KunZhi , Mao Tianqin , Deng Xuyang , Luo Qiyu , Nie Xin , Fang Qiang , Xiao WenGuang , Han Yongtao , Peng Lin 
Published: September 2022

Abstract
Esophageal squamous cell carcinoma (ESCC) has high mortality in China. The cornerstone of treatment for resectable esophageal cancer is still surgery. It is vital to find the regularity of lymph node metastasis and the value of dissection for thoracic ESCC in China, to provide a basis for accurate staging and the relationship between overall survival (OS) and lymph node dissection.
Cases were collected from 2957 patients in Sichuan Cancer Hospital & Institute Esophageal Cancer Case Management Database (SCH-ECCM Database) from January 2010 to August 2017. The stations of lymph node were referenced according to CSCO diagnosis and treatment guidelines and JES, 11th Ed. According to the frequency and patient’s survival of metastases to each station of investigated tumor location were used to calculate the Efficacy Index (EI). EI was calculated by multiplying the frequency (%) and 5-year survival rate of metastases (%) in patients, and then dividing by the number of 100.
The median follow-up time was 59.5 months. The EI was high in supraclavicular and mediastinal zones in patients with upper esophageal tumors, and the EI of 106recR was 13.72, which was the highest among lymph node stations. The EI was high in mediastinal zone followed by celiac and supraclavicular zones in patients with middle esophageal tumors, 104R with EI of 15.54 was the highest among lymph node stations. As for patients with lower esophageal tumors, the EI was high in celiac zone followed by mediastinal zones, the EI of left gastric artery was 10.86, over every lymph node stations.
The EI of right recurrent nerve lymph nodes is the highest in upper esophageal cancer, as for middle esophageal cancer right supraclavicular lymph nodes had high metastasis rate and EI, but the left gastric lymph nodes had high metastasis rate and EI in the lower esophageal cancer. Although the lymph node metastasis rate of ESCC is still high, the more efficient lymphadenectomy should be considered based on further studies.
623. A NEW PROGNOSTIC EVALUATION OF POSTOPERATIVE ESOPHAGEAL CANCER: LONG-TERM FLAIL INVESTIGATION
Authors: Tanaka Tatsuya , Ogawa Ryo , Saito Masaki , Ito Sunao , Ueno Shuhei , Okubo Tomotaka , Sagawa Hiroyuki , Tanaka Tatsuya , Takahashi Hiroki , Matsuo Yoichi , MItsui Akira , Kimura Masahiro , Takiguchi Shuji 
Published: September 2022

Abstract
Recurrence-free survival and 5-year survival rates are still commonly used as prognostic indicators for gastrointestinal cancer. We believe that there is a need to find an appropriate index to evaluate changes in health status over time in postoperative patients.
We evaluated changes in "frailty" after esophageal cancer surgery using the Kihon Checklist (KCL) developed by the Japanese Ministry of Health, Labour and Welfare, and examined risk factors for worsening health status after surgery.
Twenty-four patients (21 thoracoscopic sub-total esophagectomy, 1 mediastinoscopic sub-total esophagectomy, and 2 total laryngopharyngoesophagectomy) who underwent esophageal cancer surgery in our department from December 2019 to April 2021 were included. Patients were asked to write down their KCL before surgery and one year after surgery at an outpatient clinic, and changes over time were checked. We compared the background factors in the "maintain" group (M group) and the "worsened" group (W group), and investigated the risk factors for pre-frail and frail states one year after the surgery.
8 patients worsened from robust to pre-frail to frail and pre-frail to frail, and 16 patients maintained their condition, with 33% of them worsening. Age (M/W: 70/72, p=0.296), male (M/W: 0.88/1.0, p=0.536), BMI (M/W: 22.4/19.6, p=0.142), pStage≥3 (M/W: 0.38/0.38, p=1.0), preoperative chemotherapy (M/W: 0.69/0.63, p=1.0), operative time (M/W: 566/610 minutes, p=0.327), blood loss (M/W: 103/151 ml, p=0.342), postoperative pneumonia (M/W: 0.25/0.25, p=1.0), and cancer recurrence (M/W: 0.19/0.50, p=0.167). The preoperative blood samples were Alb (M/W: 4.3/3.8 g/dl, p=0.046), Hb (M/W: 14.2/12.8 g/dl, p=0.015) and Cre (M/W: 0.85/0.79 mg/dl, p=0.713).
At 1 year after esophageal cancer surgery, health worsened and 33% of patients were in a pre-frail or frail state. Risk factors for worsening health were low Alb and low Hb, which were not related to stage or actual age. Further study is needed to clarify risk factors for frailty.
World War I: A Phoenix Moment in the History of International Criminal Tribunals
Authors: Bohrer Ziv , Pirker Benedikt 
Published: September 2022

Abstract
The post-World War II International Military Tribunal at Nuremberg is commonly considered the first-ever international criminal tribunal. It is also often argued that the very idea of an international criminal tribunal emerged after World War I, when the first plans for such a tribunal were drawn up. This article, however, presents a very different account. It shows that international criminal tribunals did not have to wait for their conception until after World War I; nor did they come into being after World War II – they already operated during World War I and the preceding century. The article also demonstrates that the existence of such tribunals did influence the participants of the Paris Peace Conference, even though they portrayed them as novel.
Effect of repeat catheter ablation vs. antiarrhythmic drug therapy among patients with recurrent atrial tachycardia/atrial fibrillation after atrial fibrillation catheter ablation: data from CHINA-AF registry
Authors: Zhou Lu , He Liu , Wang Wei , Li Changyi , Li Songnan , Tang Ribo , Sang Caihua , Liu Nian , Jiang Chenxi , Yu Ronghui , Long Deyong , Du Xin , Dong Jianzeng , Ma Changsheng 
Published: September 2022

AbstractAimsAlthough several studies have proved that repeat catheter ablation is beneficial to recurrent atrial tachycardia (AT)/atrial fibrillation (AF) after AF catheter ablation, the hard endpoints of the effect of catheter ablation on recurrent AT/AF patients after AF catheter ablation remains unclear. Our study aims to compare the effect of catheter ablation and drug therapy on recurrent AT/AF patients after AF catheter ablation.Methods and resultsFour thousand nine hundred and thirteen consecutive patients with recurrent AT/AF after catheter ablation from the China-AF registry were enrolled. The patients were divided into two study groups: the repeat catheter ablation group and the medical therapy group. The primary endpoint is a composite of cardiovascular mortality or ischaemic stroke or major bleeding events. Secondary endpoints were each component of the primary endpoints and AF recurrence rate. Landmark analysis and Cox regression were used in the statistical analysis. We chose landmark 36 months as the primary landmark date. Over a median follow-up period of 40 ± 24 months, 4913 patients were divided into either the repeat ablation group or the medical therapy group. The cumulative incidence of the composite primary outcome was significantly lower in the repeat ablation group than the medical therapy group (adjusted hazard ratio = 0.56; 95% confidence interval: 0.35–0.89; P = 0.015) of landmark 36 months (2359 patients were included in medical therapy group and 704 patients were included in repeat ablation group at landmark 36 months). However, all secondary endpoints were not statistically different in the two groups, including cardiovascular mortality, ischaemic stroke, major bleeding events, and AF recurrence rate.ConclusionBased on this research, in recurrent AT/AF patients after a catheter ablation procedure, compared with medical therapy, repeat catheter ablation may significantly reduce the risk of the endpoint of composite cardiovascular mortality, ischaemic stroke, and major bleeding events.
Multiple Horizontal Acquisitions of Plant Genes in the Whitefly Bemisia tabaci
Authors: Gilbert Clément , Maumus Florian 
Published: September 2022

Abstract
The extent to which horizontal gene transfer (HGT) has shaped eukaryote evolution remains an open question. Two recent studies reported four plant-like genes acquired through two HGT events by the whitefly Bemisia tabaci, a major agricultural pest (Lapadula WJ, Mascotti ML, Juri Ayub M. 2020. Whitefly genomes contain ribotoxin coding genes acquired from plants. Sci Rep. 10(1):15503; Xia J, et al. 2021. Whitefly hijacks a plant detoxification gene that neutralizes plant toxins. Cell 184(7):1693–1705 e1617.). Here, we uncovered a total of 49 plant-like genes deriving from at least 24 independent HGT events in the genome of the Middle East Asia Minor 1 (MEAM1) whitefly. Orthologs of these genes are present in three cryptic B. tabaci species, they are phylogenetically nested within plant sequences, they are expressed and have evolved under purifying selection. The predicted functions of these genes suggest that most of them are involved in plant–insect interactions. Thus, substantial plant-to-insect HGT may have facilitated the evolution of B. tabaci toward adaptation to a large host spectrum. Our study shows that eukaryote-to-eukaryote HGT may be relatively common in some lineages and it provides new candidate genes that may be targeted to improve current control strategies against whiteflies.
The Riemann problem for a traffic flow model on a road with variable widths
Authors: Sheng Wancheng , Zhang Qinglong 
Published: September 2022

Abstract
We propose and investigate a model describing the traffic flow on a road with variable widths in this paper. The model, which is modified on the Aw–Rascle model, is not conservative because of the source term generated from the real traffic scenarios. The model also takes the stationary wave into considerations in the traffic flow based on the balance laws. We obtain the elementary waves of the new traffic flow model, including rarefaction waves, shock waves, contact discontinuities and particularly stationary waves. The Riemann problems to the system for the traffic flows are solved constructively, which can be further used to design numerical schemes and applied to more complex traffic flows in the future study. Some real traffic flow simulations are given, which verify the effectiveness and versatility of the model.
Pointwisea posteriorierror analysis of a discontinuous Galerkin method for the elliptic obstacle problem
Authors: Ayuso de Dios Blanca , Gudi Thirupathi , Porwal Kamana 
Published: September 2022

AbstractWe present a posteriori error analysis in the supremum norm for the symmetric interior penalty discontinuous Galerkin method for the elliptic obstacle problem. We construct discrete barrier functions based on appropriate corrections of the conforming part of the solution obtained via a constrained averaging operator. The corrector function accounts properly for the nonconformity of the approximation and it is estimated by direct use of the Green’s function of the unconstrained elliptic problem. The use of the continuous maximum principle guarantees the validity of the analysis without mesh restrictions but with shape regularity. The proposed residual-type estimators are shown to be reliable and efficient. Numerical results in two dimensions are included to verify the theory and validate the performance of the error estimator.