bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHERRY: a Computational metHod for accuratE pRediction of virus–pRokarYotic interactions using a graph encoder–decoder model
Authors: Shang Jiayu , Sun Yanni 
Published: April 2022

Abstract
Prokaryotic viruses, which infect bacteria and archaea, are key players in microbial communities. Predicting the hosts of prokaryotic viruses helps decipher the dynamic relationship between microbes. Experimental methods for host prediction cannot keep pace with the fast accumulation of sequenced phages. Thus, there is a need for computational host prediction. Despite some promising results, computational host prediction remains a challenge because of the limited known interactions and the sheer amount of sequenced phages by high-throughput sequencing technologies. The state-of-the-art methods can only achieve 43% accuracy at the species level. In this work, we formulate host prediction as link prediction in a knowledge graph that integrates multiple protein and DNA-based sequence features. Our implementation named CHERRY can be applied to predict hosts for newly discovered viruses and to identify viruses infecting targeted bacteria. We demonstrated the utility of CHERRY for both applications and compared its performance with 11 popular host prediction methods. To our best knowledge, CHERRY has the highest accuracy in identifying virus–prokaryote interactions. It outperforms all the existing methods at the species level with an accuracy increase of 37%. In addition, CHERRY’s performance on short contigs is more stable than other tools.
Characterizing HIV-Preventive, Plasma Tenofovir Concentrations—A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis Clinical Trials
Authors: Garcia-Cremades Maria , Vučićević Katarina , Hendrix Craig W , Jayachandran Priya , Jarlsberg Leah , Grant Robert , Celum Connie L , Martin Michael , Baeten Jared M , Marrazzo Jeanne , Anderson Peter , Choopanya Kachit , Vanichseni Suphak , Glidden David V , Savic Radojka M 
Published: April 2022

AbstractBackgroundDaily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration.MethodsParticipant data from TFV-based daily oral and topical active arms of phase 3 trials (iPrEx, VOICE, and Partners PrEP) were pooled (n = 2950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models.ResultsAround 50% of the individuals were estimated to be adherent, which differed from self-reported adherence (∼90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high-risk females (45.8 ng/mL) compared with high-risk males (16.1 ng/mL) and to low-risk individuals (∼7.5 ng/mL). Dosing simulations indicated that high-risk women require full adherence to maintain protective levels.ConclusionsUsing the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high-risk females need higher levels of plasma TFV to achieve HIV protection compared with males. HIV protection exceeds 90% in all populations if daily adherence is achieved.
Low Body Mass Index at Treatment Initiation and Rifampicin-Resistant Tuberculosis Treatment Outcomes: An Individual Participant Data Meta-Analysis
Authors: Campbell Jonathon R , Chan Edward D , Falzon Dennis , Trajman Anete , Keshavjee Salmaan , Leung Chi C , Miller Ann C , Monedero-Recuero Ignacio , Rodrigues Denise S , Seo Haesook , Baghaei Parvaneh , Udwadia Zarir , Viiklepp Piret , Bastos Mayara , Menzies Dick 
Published: April 2022

Abstract

Background
The impact of low body mass index (BMI) at initiation of rifampicin-resistant tuberculosis (RR-TB) treatment on outcomes is uncertain. We evaluated the association between BMI at RR-TB treatment initiation and end-of-treatment outcomes.

Methods
We performed an individual participant data meta-analysis of adults aged ≥18 years with RR-TB whose BMI was documented at treatment initiation. We compared odds of any unfavorable treatment outcome, mortality, or failure/recurrence between patients who were underweight (BMI &lt;18.5 kg/m2) and not underweight. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using logistic regression, with matching on demographic, clinical, and treatment-related factors. We evaluated effect modification by human immunodeficiency virus (HIV) status and other variables using likelihood ratio tests. We also estimated cumulative incidence of mortality during treatment stratified by HIV.

Results
Overall, 5148 patients were included; 1702 (33%) were underweight at treatment initiation. The median (interquartile range) age was 37 years (29 to 47), and 455 (9%) had HIV. Compared with nonunderweight patients, the aOR among underweight patients was 1.7 (95% CI, 1.4–1.9) for any unfavorable outcome, 3.1 (2.4–3.9) for death, and 1.6 (1.2–2.0) for failure/recurrence. Significant effect modification was found for World Health Organization region of treatment. Among HIV-negative patients, 24-month mortality was 14.8% (95% CI, 12.7%–17.3%) for underweight and 5.6% (4.5%–7.0%) for not underweight patients. Among patients with HIV, corresponding values were 33.0% (25.6%–42.6%) and 20.9% (14.1%–27.6%).

Conclusions
Low BMI at treatment initiation for RR-TB is associated with increased odds of unfavorable treatment outcome, particularly mortality.
Expression Patterns and Corepressor Function of Retinoic Acid-induced 2 in Prostate Cancer
Authors: Besler Katharina , Węglarz Aleksandra , Keller Laura , von Amsberg Gunhild , Bednarz-Knoll Natalia , Offermann Anne , Stoupiec Sara , Eltze Elke , Semjonow Axel , Boettcher Lena , Schneegans Svenja , Perner Sven , Hauch Siegfried , Todenhöfer Tilman , Peine Sven , Pantel Klaus , Wikman Harriet , Werner Stefan 
Published: April 2022

Abstract

Background
Revealing molecular mechanisms linked to androgen receptor activity can help to improve diagnosis and treatment of prostate cancer. Retinoic acid-induced 2 (RAI2) protein is thought to act as a transcriptional coregulator involved in hormonal responses and epithelial differentiation. We evaluated the clinical relevance and biological function of the RAI2 protein in prostate cancer.

Methods
We assessed RAI2 gene expression in the Cancer Genome Atlas prostate adenocarcinoma PanCancer cohort and protein expression in primary tumors (n = 199) by immunohistochemistry. We studied RAI2 gene expression as part of a multimarker panel in an enriched circulating tumor cell population isolated from blood samples (n = 38) of patients with metastatic prostate cancer. In prostate cancer cell lines, we analyzed the consequences of androgen receptor inhibition on RAI2 protein expression and the consequences of RAI2 depletion on the expression of the androgen receptor and selected target genes.

Results
Abundance of the RAI2 protein in adenocarcinomas correlated with the androgen receptor; keratins 8, 18, and 19; and E-cadherin as well as with an early biochemical recurrence. In circulating tumor cells, detection of RAI2 mRNA significantly correlated with gene expression of FOLH1, KLK3, RAI2, AR, and AR-V7. In VCaP and LNCaP cell lines, sustained inhibition of hormone receptor activity induced the RAI2 protein, whereas RAI2 depletion augmented the expression of MME, STEAP4, and WIPI1.

Conclusions
The RAI2 protein functions as a transcriptional coregulator of the androgen response in prostate cancer cells. Detection of RAI2 gene expression in blood samples from patients with metastatic prostate cancer indicated the presence of circulating tumor cells.
5: LOCAL ENDOSCOPIC RESECTION IS INFERIOR TO GASTRECTOMY FOR EARLY CLINICAL STAGE T1A AND T1B GASTRIC ADENOCARCINOMA: A PROPENSITY-MATCHED STUDY
Authors: Kamarajah S , Markar S , Phillips A , Salti G , Dahdaleh F 
Published: April 2022

Abstract

Background and aim
The role of ER in the management of subsets of clinical T1N0 gastric adenocarcinoma remains controversial. The aim of this study was to evaluate the outcome of endoscopic resection (ER) versus gastrectomy in node negative cT1a and cT1b gastric adenocarcinoma.

Methods
Data from the National Cancer Database (2010–2015), was used to identify patients with clinical T1aN0 (n = 2,927; ER, n = 1,157; gastrectomy, n = 1,770) and T1bN0 (n = 2,915; ER, n = 474; gastrectomy, n = 2,441) gastric adenocarcinoma. Propensity score matching (PSM) and Cox multivariable analyses were used to account for treatment selection bias.

Results
ER for cT1a and cT1b cancers was performed more frequently over time. Rates of node-positive disease in patients with cT1a and cT1b gastric adenocarcinoma were 5% and 18%, respectively. In the matched cohort, gastrectomy was associated with increased survival compared to ER for cT1a cancers (HR: 0.79, 95% CI: 0.66–0.95, P = 0.013), and corresponding 5-year survival for gastrectomy and ER were 72% and 66% (P = 0.013), respectively. For cT1b cancers, gastrectomy had a significantly longer survival compared to ER (HR: 0.77, 95% CI: 0.63–0.93, P = 0.008) and the corresponding 5-year survival for gastrectomy and ER were 60% and 50% (P = 0.013), respectively.

Conclusion
This study demonstrates ER inferior long-term survival for clinical T1aN0 and T1bN0 gastric adenocarcinoma, despite current recommendations for ER in cT1 gastric cancers. Future research should seek to identify the subset of T1a and T1b cancers at low risk of nodal metastasis and thus would maximally benefit from ER.
7: NEOADJUVANT CHEMORADIOTHERAPY OR CHEMOTHERAPY ALONE FOR OESOPHAGEAL CANCER: POPULATION-BASED COHORT STUDY
Authors: Kamarajah S , Phillips A , Ferri L , Hofstetter W , Markar S 
Published: April 2022

Abstract

Background and aim
Although both neoadjuvant chemoradiotherapy (nCRT) and chemotherapy (nCT) are used as neoadjuvant treatment for oesophageal cancer, it is unknown if one provides a survival advantage over the other particularly with respect to histological subtype. This study aimed to compare prognosis following nCRT and nCT in patients undergoing oesophagectomy for oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC).

Methods
Data from the National Cancer Database (2006 to 2015) were used to identify patients with OAC (n = 11,167; nCRT 9,972 (89%), nCT 1,195 (11%)) and OSCC (n = 2,367; nCRT 2 m155 (91%), nCT 212 (9%)). Propensity score matching and Cox multivariable analyses were used to account for treatment selection biases.

Results
In the matched cohort for OAC, nCRT provided higher rates of complete pathological response (35% vs. 21%, P &lt; 0.001) and margin-negative resections (90% vs. 86%, P &lt; 0.001). However, nCRT had similar survival to nCT (Hazard ratio (HR):1.04, 95% confidence interval (CI):0.95–1.14). The corresponding 5-year survival for nCRT and nCT were 36% and 37% (P = 0.1), respectively. For OSCC, nCRT had higher rates of complete pathological response (51% vs. 30%, P &lt; 0.001) and margin-negative resections (93% vs. 82%, P &lt; 0.001). nCRT had a statistically significant overall survival benefit (HR: 0.78, 95% CI: 0.62–0.97). The 5-year survival for nCRT and nCT were 45% versus 38% (P = 0.026), respectively.

Conclusion
Despite pathological benefits including primary tumour response from nCRT, there was no prognostic benefit to nCRT compared to nCT for OAC suggesting both modalities are equally acceptable. However, for OSCC, nCRT followed by surgery appears to remain the optimal treatment approach.
128: DECIPHERING THE IMMUNOLOGICAL DETERMINANTS OF RESPONSE TO NEOADJUVANT CHEMO-RADIATION IN ESOPHAGEAL ADENOCARCINOMA
Authors: Arbore G , Albarello L , Bucci G , Punta M , Bilello V , Bonfiglio S , Fanti L , Cossu A , Tonon G , Rosati R , Casorati G , Dellabona P 
Published: April 2022

Abstract

Background and aim
The standard therapy for esophageal adenocarcinoma (EAC) is pre-operative neoadjuvant chemo-radiation (NACR) and surgery. Less that 30% of patients achieve a pathological complete response (pCR) and increased 5-year survival after NACR. Understanding the mechanisms of response to NACR is pivotal to better stratify patients and inform the design of more efficacious therapies. Cancer progression partly depends on defective immune surveillance, and the presence of tumor infiltrating T lymphocytes (TILs) is associated with better prognosis of several malignancies. We hypothesize that NACR induces immunogenic cell death that stimulates immune responses against tumor neoantigens (TNAs), derived from cancer somatic mutations, in the responders. We thus compared responders and non-responders for tumor immune contexture, immune molecular pathways, circulating immune markers and TNAs-specific T cells responses.

Methods
Pre-NACR tumor biopsies prospectively collected from consecutive EAC patients were subjected to DNA whole exome and RNA sequencing, high dimensional (HD) multiparametric flow cytometry and immune contexture analysis by histology and by proteome digital spatial profiling (n = 53 targets), while their peripheral blood mononuclear cells and plasma collected pre- and post- NACR were analyzed by HD flow cytometry and cytokine multiplexing assay respectively.

Results
Treatment-naïve EACs of NACR responders showed higher TNA load and enriched immune signatures compared to non-responders. Moreover, pre-treatment EACs of responders demonstrate augmented effector T cell infiltration and reduced Treg cells and M2-like pro-tumoral macrophages. High M2-like macrophages score associated with lower overall survival. Increased frequencies of circulating myeloid suppressor populations were detected both at baseline and after NACR in non-responder patients. These observations were associated with circulating levels of n = 30 cytokines/chemokines and with spatial expression of immune markers in tumor biopsies.

Conclusion
Collectively, these results support pre-existing immune-mediated mechanisms of anti-tumor response stimulated by NACR in the fraction of responder EAC patients, suggesting possible ways to stratify patients and direct them to more tailored neoadjuvant and/or adjuvant treatments, possibly in combination with personalized immunotherapy approaches.
176: YAP/TAZ ACTIVATION IS A MECHANISM OF TUMOR PROGRESSION IN THE POORLY COHESIVE GASTRIC CANCER PHENOTYPE
Authors: Sacco M , Bencivenga M , Torroni L , Tomezzoli A , Castelli C , Alloggio M , Verlato G , Giacopuzzi S , Iglesias M , Pera M , De Manzoni G , Melisi D 
Published: April 2022

Abstract

Background and aim
Poorly Cohesive Gastric Cancer (PC-GC), according with the latest WHO classification, has a poor prognosis and its relative incidence is increasing. Disregulation of the Hippo pathway and/or activation of YAP/TAZ signaling pathway are emerging as central determinants for tumor initiation, progression and chemoresistance. The role of YAP/TAZ in human GC has not been defined to date. We hypothesized that RhoA-YAP/TAZ axis is a mechanisms of tumor progression in PC-GC, influencing prognosis.

Methods
We retrospectively analysed 131 PC-GC patients, treated at two European surgical centres from 2004 to 2014. YAP/TAZ nuclear expression was analysed with immunohistochemistry. Both YAP and TAZ nuclear expression was coded as ‘negative’ (complete absence of nuclear reactivity) or ‘any positive’ (both low and high nuclear expression).

Results
21 patients showed absence of nuclear reactivity YAP−/TAZ-, while 110 showed any positivity: YAP+ (85/133 = 63.9%), TAZ+ (93/131 = 69.9%). Pathological tumor stage were significantly earlier in YAP−/TAZ- patients; 38% of YAP−/TAZ- were pT1–2 compared with only 17% of cases showing any expression (P = 0.041). Patients without nuclear YAP/TAZ expression were pN0 in 55% of cases compared with 26% of cases with any positive nuclear reaction (P = 0.020). In negative group 5-year OS was 57% compared with 29% in any positive group (P = 0.030). 5-year survival was the highest in YAP−/TAZ- group, intermediate when only one of the two biomarkers was expressed, and the lowest in YAP+/TAZ+ group (P = 0.010).

Conclusion
Nuclear negativity to both YAP and TAZ identify a subgroup of PC-GC with more favourable prognosis. Higher clinic-pathological stage and a worse OS was associated to YAP/TAZ positive patients supporting the involvement of this pathway in the progression of PC gastric carcinoma. Our results provide new insights into the role of YAP/TAZ signalling cascade as a mechanism of cancer progression in sporadic PC-GC.
177: A 5-YEAR SINGLE CENTER EXPERIENCE IN ROBOTIC SURGERY FOR ESOPHAGEAL ACHALASIA IN A TERTIARY CENTER, WITH PERI-OPERATIVE TAILORED PROTOCOLS
Authors: Voltarel G , Guerzoni G , Zenzaro M , Beber A , Veltri A , Casella F , Giacopuzzi S 
Published: April 2022

Abstract

Background and aim
Esophageal achalasia is a rare benign disease with heavy impact on daily life. Laparoscopic Heller-myotomy as the gold standard surgical treatment. In recent years the robot-assisted (DaVinci, Intuitive Surgical Inc., CA) technique became widely used for its reported advantages in terms of vision, precision and motion. The aim of the study was to evaluate the supposed advantages of robot-assisted Heller myotomy compared to the standard laparoscopic approach in a single center experience.

Methods
We included the patients who underwent standard laparoscopic and robot-assisted Heller-myotomy with Dor fundoplicatio in the last 5 years in the Upper-GI division of the University Hospital of Verona. We assessed if the robot-assisted Heller-Dor myotomy was simplified in terms of the ease of the myotomy, especially on the gastric side and the following fundoplicatio, on the sharpness of the endoscope and on the precision of the movements. We also compared the operative times with the two techniques, and the overall morbidity and mortality rates, also with the introduction of new peri-operative protocols for standardized and enhanced recovery.

Results
We included 40 patients who underwent Heller-Dor, robot-assisted Heller-Dor approach was performed in 17 patients and standard laparoscopic approach in 23 patients. Based on the surgeons experience and judgment, robot-assisted Heller-myotomy seems to be easier than the laparoscopic procedure in terms of sharpness of vision, freedom of motion and consequently precision in the single-fibers dissection of the muscularis. The operative times were comparable between the robot-assisted procedures and the laparoscopic approach, as were morbidity and mortality rates; in-hospital stay was also similar in the two groups, with a slight decrease in the last 6 months, after the introduction of new post-operative protocols for enhanced recovery with mandatory contrast swallow on POD1.

Conclusion
Our study suggests that robot-assisted Heller-myotomy for achalasia is a valid alternative to the traditional laparoscopic approach, for the improvement of surgical precision and myotomy outcome, with apparently no deterioration of safety and surgical complications, in particular with dedicate personnel and standardized recovery protocols. It also suggests that the learning curve is negligible if supported by an adequate number of patients per-year, as in a tertiary center.
Timing of cardiac surgery during pregnancy: a patient-level meta-analysis
Authors: van Steenbergen Gijs J , Tsang Queeny H Y , van der Heijden Olivier W.H. , Vart Priya , Rodwell Laura , Roos-Hesselink Jolien W , van Kimmenade Roland R J , Li Wilson W L , Verhagen Ad F T M 
Published: April 2022

Abstract

Aims
To investigate the association between the timing of cardiac surgery during pregnancy and both maternal and foetal outcomes.

Methods and results
Studies published up to 6 February 2021 on maternal and/or foetal mortality after cardiac surgery during pregnancy that included individual patient data were identified. Maternal and foetal mortality was analysed per trimester for the total population and stratified for patients who underwent caesarean section (CS) prior to cardiac surgery (Caesarean section (CaeSe) group) vs. patients who did not (Cardiac surgery (CarSu) group). Multivariable logistic regression analysis was performed to evaluate predictors of both maternal and foetal mortality. In total, 179 studies were identified including 386 patients of which 120 underwent CS prior to cardiac surgery. Maternal mortality was 7.3% and did not differ significantly among trimesters of pregnancy (P = 0.292) nor between subgroup CaeSe and CarSu (P = 0.671). Overall foetal mortality was 26.5% and was lowest when cardiac surgery was performed during the third trimester (10.3%, P &lt; 0.01). CS prior to surgery was significantly associated with a reduced risk of foetal mortality in a multivariable model [odds ratio 0.19, 95% confidence interval [0.06–0.56)]. Trimester was not identified as an independent predictor for foetal nor maternal mortality.

Conclusion
Maternal mortality after cardiac surgery during pregnancy is not associated with the trimester of pregnancy. Cardiac surgery is associated with high foetal mortality but is significantly lower in women where CS is performed prior to cardiac surgery. When the foetus is viable, CS prior to cardiac surgery might be safe. When CS is not feasible, trimester stage does not seem to influence foetal mortality.
Cooperative multinetworks semi-supervised pre-stack seismic inversion
Authors: Song Lei , Yin Xingyao , Zong Zhaoyun , Feng Yanwen 
Published: April 2022

SUMMARY
The elastic properties of the subsurface, such as density, P-velocity and S-velocity, can be estimated in pre-stack seismic inversion. In recent research, the deep neural network is widely used in pre-stack seismic inversion for its strong non-linear fitting and feature extraction ability. However, the label data is generally inadequate due to high drilling costs and strong data-sharing barriers in the field of exploration geophysics. In order to reduce the dependence of network performance on label data and ensure the accuracy of inversion mostly, semi-supervised learning is adopted. Here, we develop a cooperative multinetworks semi-supervised pre-stack seismic inversion method. In the cooperative multinetworks inversion framework, the inversion network, mapping network, and modification network are adopted to complete the inversion task cooperatively. A forward network is constructed to automatically generate seismic data from density, P-velocity and S-velocity, which can assist the above networks to complete semi-supervised learning. Compared with some published deep learning pre-stack inversion methods, the spatio-temporal correlation of data can be fully mined, the prior geological structure and low-frequency information can be utilized effectively, and reflectivity is adopted as an intermediate output parameter to improve the robustness of the method. The experiments on the Marmousi2 model demonstrate that cooperative multinetworks semi-supervised inversion strategy is superior to conventional semi-supervised inversion methods in both inversion accuracy and antinoise performance. In addition, the susceptibility experiments of the initial model indicate that the proposed method can maintain a high inversion accuracy with little effective information in the initial model. Finally, the proposed method is successfully applied to the field data and obtains a high-resolution inversion result.