bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer-aided prediction and design of IL-6 inducing peptides: IL-6 plays a crucial role in COVID-19
Authors: Dhall Anjali , Patiyal Sumeet , Sharma Neelam , Usmani Salman Sadullah , Raghava Gajendra P S 
Published: September 2020

Abstract
Interleukin 6 (IL-6) is a pro-inflammatory cytokine that stimulates acute phase responses, hematopoiesis and specific immune reactions. Recently, it was found that the IL-6 plays a vital role in the progression of COVID-19, which is responsible for the high mortality rate. In order to facilitate the scientific community to fight against COVID-19, we have developed a method for predicting IL-6 inducing peptides/epitopes. The models were trained and tested on experimentally validated 365 IL-6 inducing and 2991 non-inducing peptides extracted from the immune epitope database. Initially, 9149 features of each peptide were computed using Pfeature, which were reduced to 186 features using the SVC-L1 technique. These features were ranked based on their classification ability, and the top 10 features were used for developing prediction models. A wide range of machine learning techniques has been deployed to develop models. Random Forest-based model achieves a maximum AUROC of 0.84 and 0.83 on training and independent validation dataset, respectively. We have also identified IL-6 inducing peptides in different proteins of SARS-CoV-2, using our best models to design vaccine against COVID-19. A web server named as IL-6Pred and a standalone package has been developed for predicting, designing and screening of IL-6 inducing peptides (https://webs.iiitd.edu.in/raghava/il6pred/).
Supervised learning on phylogenetically distributed data
Authors: Layne Elliot , Dort Erika N , Hamelin Richard , Li Yue , Blanchette Mathieu 
Published: September 2020

Abstract

Motivation
The ability to develop robust machine-learning (ML) models is considered imperative to the adoption of ML techniques in biology and medicine fields. This challenge is particularly acute when data available for training is not independent and identically distributed (iid), in which case trained models are vulnerable to out-of-distribution generalization problems. Of particular interest are problems where data correspond to observations made on phylogenetically related samples (e.g. antibiotic resistance data).

Results
We introduce DendroNet, a new approach to train neural networks in the context of evolutionary data. DendroNet explicitly accounts for the relatedness of the training/testing data, while allowing the model to evolve along the branches of the phylogenetic tree, hence accommodating potential changes in the rules that relate genotypes to phenotypes. Using simulated data, we demonstrate that DendroNet produces models that can be significantly better than non-phylogenetically aware approaches. DendroNet also outperforms other approaches at two biological tasks of significant practical importance: antiobiotic resistance prediction in bacteria and trophic level prediction in fungi.

Availability and implementation
https://github.com/BlanchetteLab/DendroNet.
Risk of Incident Diabetes Mellitus, Weight Gain, and Their Relationships With Integrase Inhibitor–Based Initial Antiretroviral Therapy Among Persons With Human Immunodeficiency Virus in the United States and Canada
Authors: Rebeiro Peter F , Jenkins Cathy A , Bian Aihua , Lake Jordan E , Bourgi Kassem , Moore Richard D , Horberg Michael A , Matthews W Christopher , Silverberg Michael J , Thorne Jennifer , Mayor Angel M , Lima Viviane D , Palella Frank J , Saag Michael S , Althoff Keri N , Gill M John , Wong Cherise , Klein Marina B , Crane Heidi M , Marconi Vincent C , Shepherd Bryan E , Sterling Timothy R , Koethe John R 
Published: September 2020

Abstract

Background
Integrase strand transfer inhibitor (INSTI)–based combination antiretroviral therapy (cART) is associated with greater weight gain among persons with human immunodeficiency virus (HIV), though metabolic consequences, such as diabetes mellitus (DM), are unclear. We examined the impact of initial cART regimen and weight on incident DM in a large North American HIV cohort (NA-ACCORD).

Methods
cART-naive adults (≥18 years) initiating INSTI-, protease inhibitor (PI)–, or nonnucleoside reverse transcriptase inhibitor (NNRTI)–based regimens from January 2007 through December 2017 who had weight measured 12 (±6) months after treatment initiation contributed time until clinical DM, virologic failure, cART regimen switch, administrative close, death, or loss to follow-up. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DM by cART class. Mediation analyses, with 12-month weight as mediator, similarly adjusted for all covariates.

Results
Among 22 884 eligible individuals, 47% started NNRTI-, 30% PI-, and 23% INSTI-based cART with median follow-up of 3.0, 2.3, and 1.6 years, respectively. Overall, 722 (3%) developed DM. Persons starting INSTIs vs NNRTIs had incident DM risk (HR, 1.17 [95% CI, .92–1.48]), similar to PI vs NNRTI initiators (HR, 1.27 [95% CI, 1.07–1.51]). This effect was most pronounced for raltegravir (HR, 1.42 [95% CI, 1.06–1.91]) vs NNRTI initiators. The INSTI–DM association was attenuated (HR, 1.03 [95% CI, .71–1.49] vs NNRTIs) when accounting for 12-month weight.

Conclusions
Initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of DM, likely mediated through weight gain.
Public attribution of cyber intrusions
Authors: Egloff Florian J 
Published: September 2020

Abstract
Attribution is central to the debate on how to respond to cyber intrusions. The policy challenge is increasingly moving from identifying who is behind a cyber intrusion to finding the adequate policy response, including whether to publicly attribute. The article examines the use of public attribution as a political strategy for attaining specific political effects beyond the dyadic attacker–victim relationship, including shaping the operational and normative environment of cyber operations, with the potential to exert an independent deterrent effect. My analysis unfolds in three parts. The first part introduces two core concepts—sense-making and meaning-making—to capture different parts of the attribution process. I then introduce a theoretical understanding of public attribution drawing on the literature on revealing covert activity and argue that public attribution can serve the function of defining a particular interaction order, i.e. shape the rules of the ‘game’. In part two and three I discuss two empirical examples of both concepts. I bring to the fore three observations: First, some states have shifted their policy responses from dealing with individual cyber intrusions to responding in a broader political framework of relations with a specific adversary leading to campaign-like responses. Second, the political decision whether to attribute publicly is not only a signal to the adversary, but also aims at shaping the future political and normative operational environment. Third, such norm shaping has the potential to exert an independent—though limited—deterrent effect, particularly on potential adversaries. The analysis demonstrates the importance of the meaning-making process to understanding the politics of attribution and the rewards of theoretically integrating it into the politics of secrecy and exposure of covert activities of states.
408 THE PRESENCE OF LYMPHATIC, VENOUS AND PERINEURAL INFILTRATION FOLLOWING ESOPHAGECTOMY WITHOUT NEOADJUVANT THERAPY TO IDENTIFY PATIENTS AT RISK OF RECURRENCE.
Authors: Hardy K , Chmelo J , Khaw R , Navidi M , Phillips A 
Published: September 2020

Abstract

Staging and prognostication in esophgaeal cancer patients is based on their TNM stage. Previous research has suggested venous invasion (VI), lymph vessel invasion (LI) and perineural invasion (PNI) as adverse prognostic indicators in patients with advanced disease receiving neoadjuvant treatment. The aim of this study was to assess the incidence and prognostic significance of these factors in patients with cancer of the esophagus or gastro-esophageal junction (GEJ) who were treated with unimodality surgery.

Methods
A contemporaneously maintained database was used to identify patients who underwent a primary 2-field transthoracic esophagectomy for adenocarcinoma or squamous cell carcinoma of the esophagus or gastro-esophageal junction. Between January 2000 and January 2018. Patients who died in hospital, underwent palliative resections or where the presence (or absence) of VI, LI or PNI was not reported were excluded. Patients were staged using UICC-TNM 7.

Results
279 patients were included. VI was present in 99 (35%) patients, LI in 120 (43%), and PNI in 120 (43%). Median overall survival was 140 months (95% confidence interval (CI): 79.3–200.7) when PNI, LV and VI were absent, 55 months (95% CI: 42.2–67.8) when one factor was present, 18 months (95% CI: 5.4–30.6) with two factors and 31 months (95% CI: 17.6–44.4) with all three factors present. Univariable analysis revealed that LI, PNI and VI are significant prognostic indicators for length of disease-free survival (p &lt; 0.001) with LI an independent prognostic factor on multivariable analysis (p = 0.05).

Conclusion
These findings suggest the importance of the presence of LI, VI and PNI in patients undergoing unimodality esophagectomy for cancer of the esophagus. It may provide additional information for identifying patients that are high risk who may be candidates for adjuvant therapy.
452 SURVIVAL IMPACT OF CLINICALLY NEGATIVE BUT PATHOLOGICALLY POSITIVE NODES IN CSTAGE I ESOPHAGEAL CANCER PATIENTS
Authors: Momose K , Shiraishi O , Hiraki Y , Kato H , Iwama M , Yasuda A , Shinkai M , Imano M , Yasuda T 
Published: September 2020

Abstract

Clinical diagnosis of lymph node metastasis has a great significance particularly in cT1 or cT2 esophageal cancer patients, since their clinical “N” diagnosis determines the treatment strategy according to the Esophageal cancer practice guidelines 2017 edited by the Japan Esophageal Society. Then clinically node-negative but pathologically node-positive status could potentially have negative impact on survival outcome. The purpose of this study is to see the impact of clinical node diagnosis.

Methods
Esophageal squamous cell carcinoma patients diagnosed as cT1N0 or cT2N0 who underwent radical esophagectomy from 2003 to 2017 were enrolled retrospectively. Clinically node-positive was defined as any of the followings; 1) 10 mm or more longest diameter, 2) 8 mm or more longest diameter and round or irregular shaped, 3) 5 mm or more longest diameter and FDG uptake on PET-CT scan. Survival curves with Kaplan–Meier method were plotted by the pathological N stage and examined by the log rank test.

Results
Totally 203 patients were enrolled in this study. There were 159(78%)/36(18%)/8(4%)/0(0%) pN0/pN1/pN2/pN3 patients, respectively. There was no significant survival difference between pN0 and pN1 patients (p = 0.9). But pN2 patients had worse survival than pN0 patients (p = 0.0037).

Conclusion
There was no negative survival impact of two or less clinically negative but pathologically positive nodes. This might suggest that clinical node diagnosis should be assessed carefully enough in order to have as less number of clinically negative but pathologically positive nodes as possible. Further investigation is needed for those having three or more clinically negative but pathologically positive nodes.
471 POTENTIAL ROLE OF NEOADJUVANT RADIO-CHEMOTHERAPY ON NEW-ONSET ATRIAL FIBRILLATION AFTER HYBRID IVOR-LEWIS ESOPHAGECTOMY FOR CANCER
Authors: Pansa A , Riva P , Da Roit A , Basato S , Ricchitelli S , Luberto A , Marano S , Castoro C 
Published: September 2020

Abstract

New onset atrial fibrillation (AF) is observed in up to 37% of patients after esophagectomy for esophageal and esophago-gastric junction (EGJ) cancer. Little is known about risk factors for AF in this cohort of patients. Current literature describes an association between postoperative AF and other complications, notably anastomotic leaks and infective or pulmonary complications. The aim of this paper is to determine which factors relate to an increased risk of new-onset AF after esophagectomy.

Methods
We retrospectively analyzed a prospectively collected database in a high-volume, tertiary referral center for esophageal disease. All consecutive patients who underwent hybrid Ivor-Lewis (IL) esophagectomy for esophageal or EGJ cancer at the Upper GI surgery unit in Humanitas Research Hospital from January 2018 to august 2019 were evaluated for inclusion. Patients with a history of paroxysmal or chronic AF were excluded from the analysis. Complications were reported according to the ECCG classification. Association between variables and onset of AF was studied with univariable and multivariable logistic regression analysis.

Results
89 IL cases among 125 esophagectomies were included for analysis. Overall complication rate was 29.2%. AF accounted for 9 cases (10.1%) and was the only complication in these patients. Anastomotic leak occurred in 2 patients (2.25%) both ECCG type 1, 3 developed significant pleural effusion (3.37%), 6 other infective conditions (6.7%). No postoperative deaths occurred. Significantly increased risk of AF was found in patients who underwent chemoradiotherapy(CRT) compared to those who received chemotherapy(CT) or no treatment(OR = 8.4, p = 0.02). If we compare only patients who received neoadjuvant treatment, a higher risk for CRT versus CT alone was found(OR = 5.5), with a trending significance(p = 0.08).

Conclusion
In this study, we did not find any association between AF and other complications. New-onset AF always presented as the only complication and it was significantly associated to neoadjuvant chemoradiotherapy. On the basis of this findings, we are designing a protocol with the aim of studying potential preventive intervention for postoperative FA after esophagectomy.
474 GENOMIC ANALYSIS OF RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN ESOPHAGEAL ADENOCARCINOMA
Authors: Izadi F , Devonshire G , Walker R , Lloyd M , Gibson J , Secrier M , Fitzgerald R , Rose-Zerilli M , Underwood T 
Published: September 2020

Abstract

In the UK, neoadjuvant chemotherapy (NAC) for locally advanced esophageal adenocarcinoma (EAC) is the standard of care. Unfortunately, response to NAC, following surgery is often low (&lt;30%) and survival benefit at 2 years is only 5.1%. The EAC genome is complex and heterogeneous between patients, where specific mutagenic processes and mutations may result in chemotherapy resistance. Here we report preliminary results from whole-genome sequencing (WGS) of 48 patients who were subsequently treated with NAC.

Methods
We defined response as Mandard Tumor Regression Grade (TRG) 1-2 (n = 15) and non-response as TRG4-5 (n = 33). WGS of 50x coverage and calling of genomic events (Strelka2, SCAT/GISTIC) was performed according to Frankell Nat Genet 2019 with modifications, to differentiate driver from passenger mutations (dNdScv, oncodriveCLUST), determine variant allele frequencies (VAF; copy number-adjusted) and mutation signatures (NMF R-package). Following stringent variant QC (Phred score ≥ 30), filtering (VAF &gt;0.02) and annotation (ANNOVAR, cancer census/helper, the 77 known EAC drivers and false positive genes) and visualisation in maftools, we evaluated the data for associations between genomic events and response to NAC.

Results
COSMIC mutation signatures 2 (TRG1-2; Cosθ = 0.89) and 6 (TRG4-5; Cosθ = 0.82) were enriched, suggesting defective mismatch repair in non-responders. Using 5,193 high-confidence non-silent mutations (TRG1-2,n = 1969; TRG4-5, n = 3224), we identified 39 mutated driver genes (Figure-1) with a median of 2.9(0-5) (TRG1-2) and 2.7(0-9) (TRG4-5) driver events/patient. Shared dysregulated pathways, included DNA-damage (TP53), cell cycle (CDKN2A), TGF-β (SMAD4) and chromatin regulation (ARID1A). There was no difference in the prognostic of SMAD4 and GATA4 genes. Interestingly, NAV3 mutations were only present in non-responders (21%,7/33); and in responders TP53 incidence was higher (93% vs. 58%) with a concomitant reduction in clonal cell fraction (0.25 vs. 0.39;Wilcoxon, p &lt; 0.0001).

Conclusion
The data suggest that specific genomic events, such as NAV3 mutation and the intra-tumoral heterogeneity of mutated DNA-damage response genes may offer additional predictive value. Ongoing work includes analysis of the impact of non-coding variation on response. While our analysis is limited by sample size and requires validation in additional cohorts, it demonstrates the potential of genomic sequencing to identify NAC response biomarkers and may guide alternative or novel treatment modalities for chemo-resistant tumours.
496 THE INFLAMMATORY-METAPLASIA-DYSPLASIA-OESOPHAGEAL ADENOCARCINOMA SEQUENCE: THE ROLE OF THE MICROBIOME
Authors: Barrett M , Elliott J , Hand C , Shanahan F , O'Toole P , Murphy T 
Published: September 2020

Abstract

The human microbiota, the collection of microbes that inhabit the human body, is increasingly recognized as playing a role in human health. A seminal example of this relationship is Helicobacter pylori and gastric cancer oncogenesis. The decline in H.pylori prevalence and non-cardia gastric cancer incidence have coincided with the rise in oesophageal adenocarcinoma (OAC) incidence. We sought to explore the relationship between the gastric and oesophageal microbiome and OAC oncogenesis.

Methods
This study aimed to explore changes in the microbiome associated with oesophageal adenocarcinoma and its precancerous and inflammatory states by performing 16S rRNA gene amplicon sequencing on DNA extracted from oesophago-gastric biopsies from patients with normal oesophageal mucosa, reflux oesophagitis, Barrett’s oesophagus with and without dysplasia, locally advanced but resectable oesophageal adenocarcinoma, and incurable metatstatic oesophageal adenocarcinoma (See Table 1).
We dissected ecological differences between sample site and clinical classification using a variety of approaches including examining differentially abundant taxa and inferred metabolic pathways, alpha diversity and beta-diversity.

Results
There was no statistically significant difference in beta diversity with respect to biopsy location. Alpha diversity was reduced in gastric biopsies compare to oesophageal biopsies. A small but significant shift was noted in beta diversity (Bray–Curtis Dissimilarity) with respect to clinical classification in biopsies derived from the gastroesophageal junction (GEJ) and stomach.
Fusobacterium nucleatum was found to overrepresented in oesophageal biopsies derived from diseased groups relative to the healthy controls. Several taxa assigned to the genus Prevotella were depleted in biopsies of individuals with metastatic OAC compared to all other groups.

Conclusion
Community structure was shifted in samples derived from the GEJ, the epicentre of OAC oncogenesis. Fusobacterium plays a role in cancer development and progression through a number of mechanisms including increasing cell proliferation, immune cell infiltration and chemoresistance. Fusobacterium can cause upregulation of MicroRNA-21, a microRNA upregulated in OAC.
499 SUSTAINED ESOPHAGEAL CONTRACTIONS (SEC) BY FLIP PROVIDES ADDITIONAL CHARACTERISTICS ON ESOPHAGEAL DYSMOTILITY IN PATIENTS WITH ESOPHAGEAL SYMPTOMS
Authors: Nguyen A , Zhang J , Harris S , Podgaetz E , Ward M , Ramesh M , Souza R , Spechler S , Konda V 
Published: September 2020

Abstract

Sustained esophageal contractions (SEC) have previously been described on high frequency esophageal ultrasound, high resolution manometry (HRM), and more recently on real time impedance planimetry with functional lumen imaging probe (FLIP). SEC may demonstrate a discoordination between circular and longitudinal esophageal smooth muscle contractions. The aim of this study was to determine the clinical characterization of SEC as detected on FLIP compared to HRM.

Methods
We performed a retrospective chart review of patients who underwent both FLIP and HRM at our Center for Esophageal Diseases between May 2017 and November 2019. FLIP endoscopic reports were reviewed for the presence of SECs which were defined as vigorous lumen closure ≥5 seconds at the LES or esophageal body as noted by the endoscopist during the real time FLIP examination of a sedated endoscopy. Primary variables recorded included EGJ distensibility index (EGJ-DI), diameter, and the presence of SECs at the 40 mL and 60 mL fill volumes. HRM diagnosis, clinical symptoms and outcomes were also reviewed.

Results
Of 165 patients who underwent HRM and FLIP imaging, 64 patients (mean age 53.7 years, 20 male) with SECs were included in the study. Among these patients, HRM demonstrated a wide variety of motility disorders (Figure 1). 40% of those with EGJOO, Type II or Type III achalasia, and all patients with jackhammer esophagus had SECs on FLIP imaging.
Of 56 patients with normal motility or IEM, 22 had SECs, and 18 patients underwent an endoscopic intervention. Among those who had an intervention, 11 (61%) reported improvement in symptoms with improvement in Eckardt score from 4.9 to 3.9.

Conclusion
SECs are frequently present in hypercontractile esophageal disorders. Interestingly, 39% of patients with normal motility or IEM have SECs noted on FLIP, and 82% of these patients had an intervention performed based on FLIP findings with 61% reporting symptom improvement. Overall, 19% of patients with normal motility or IEM improved due to interventions performed based on SECs found on FLIP. Detection of SEC during FLIP imaging can guide treatment aimed at relaxation of esophageal muscles.
512 OUTCOME OF MULTIMODAL TREATMENT FOR SOLITARY LYMPH NODE RECURRENCE OF ESOPHAGEAL CARCINOMA AFTER CURATIVE RESECTION
Authors: Shoda K 
Published: September 2020

Abstract

Patients with esophageal squamous cell carcinoma (ESCC) often display recurrence in the solitary lymph nodes after surgery. The optimal treatment strategy for these patients has not been established. The aim of the present study was to evaluate the outcome of intensive treatment for recurrent lymph node metastasis retrospectively.

Methods
Of the 19 patients with solitary recurrent lymph node metastasis after curative esophagectomy between 2006 and 2015, 7 had cervical lymph node, 7 had mediastinal lymph node, and 5 had abdominal lymph node recurrence. Multimodal treatment was performed in the patients: 2 patients underwent lymphadenectomy with adjuvant therapy, and 15 received definitive chemoradiotherapy and repeated chemotherapy. The remaining 2 patients received chemotherapy.

Results
Survival of lymphadenectomy group tended to be better than that of other groups (p = 0.1388), and survival of the lymphadenectomy and the chemoradiotherapy groups was significantly better than that of the patients who received chemotherapy (p = 0.0209).
Partial response (PR), stable disease, and progressive disease were obtained in 8 (53%), 1 (7%), and 6 (40%) patients who received chemoradiotherapy, respectively. Among chemoradiotherapy groups, patients with a therapeutic effect (PR) on radiation therapy had significantly better prognosis (p = 0.0175).

Conclusion
Multimodal treatment including lymphadenectomy and chemoradiotherapy could improve survival of the patients with solitary lymph node recurrence of esophageal carcinoma after curative resection.