bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does being on HIV antiretroviral therapy increase the risk of syphilis? An analysis of a large national cohort of MSM living with HIV in England 2009–2016
Authors: Allen Hester , Kirwan Peter , Brown Alison E , Mohammed Hamish , Hughes Gwenda , Marks Michael , Delpech Valerie 
Published: November 2020

Objective
A resurgence in bacterial STIs, notably syphilis, among gay, bisexual and other men who have sex with men (MSM) has been detected in England. A Canadian modelling study postulated that antiretroviral therapy (ART) may increase susceptibility to syphilis. We assess the association between ART and syphilis incidence in a comprehensive national cohort of MSM living with HIV in England.

Methods
National surveillance data were used to create a cohort of MSM attending for both HIV and STI care in England between 2009 and 2016. Survival analysis was used to calculate the incidence of infectious syphilis during periods on and off ART. Multivariable Poisson regression was used to assess the association between ART use and syphilis, after adjustment for potential confounders, including, as a proxy measure for high-risk behaviour, being diagnosed with >1 other STI prior to a syphilis diagnosis.

Results
19 428 HIV diagnosed MSM contributed 112 960 person-years of follow-up from 2009 to 2016. The overall rate of syphilis was 78.0 cases per 1000 person-years follow-up. Syphilis rates were higher among men receiving ART (36.8) compared with those who did not (28.4) (absolute rate difference 4.7 cases per 1000 person-years). Multivariable analysis showed no statistical association between receiving ART and syphilis. Increased risk of syphilis was found in MSM aged 25–34 (HR 1.89, 95% CI 1.43 to 2.51) and in those diagnosed with two other STIs (HR 5.83, 95% CI 5.37 to 6.32).

Conclusion
While we observed a small increase in the rate of syphilis among those on ART, when adjusting for potential confounding factors, including a proxy measure for high-risk behaviour, there was no evidence of an increased risk of syphilis in MSM receiving ART. High-risk sexual behaviour markers were the main risk factors for syphilis, and our results highlight the need for STI prevention interventions in MSM living with HIV to target these particularly high-risk sexual networks.
Ask Dr Google: what STI do I have?
Authors: Lee Pin Ming , Foster Rosalind , McNulty Anna , McIver Ruthy , Patel Prital 
Published: November 2020

ObjectivesBetween 2013 and 2014, a third of Australian adults reported using the internet to investigate medical symptoms before consulting a medical practitioner. However, there is limited evidence regarding internet health information seeking behaviour (HISB) in sexual health. This study aims to determine the frequency, predictors and accuracy of internet HISB for sexual health self-diagnosis.MethodsA cross-sectional paper-based survey, available in English, Chinese and Thai, was conducted during April to August 2019 at the Sydney Sexual Health Centre (SSHC). Symptomatic patients were recruited to answer an 18-item survey on their HISB, self-assessed diagnosis, anxiety and health literacy. Survey responses were correlated with SSHC electronic medical record data including participant demographics and clinician diagnosis. Data analyses were performed using Stata V.14.ResultsThe majority of participants searched the internet (355; 79.1%) before attending clinic, and of these only 16.9% made a correct self-diagnosis. Multivariate analyses demonstrated that relative to Australian-born participants, people born in Asia were twice as likely to undertake internet HISB (adjusted OR (AOR) 2.41, 95% CI 1.25 to 4.64, p<0.01), and those born in Latin America were more likely to self-diagnose correctly (AOR 3.35, 95% CI 1.20 to 9.37, p<0.01). On average, participants who searched the internet scored higher relative to those who did not search, on measures of feeling generally tense (2.26, 95% CI 2.16 to 2.7 and 1.86, 95% CI 1.67 to 2.05, p<0.001), upset (1.96, 95% CI 1.85 to 2.08 and 1.53, 95% CI 1.35 to 1.72, p<0.001) and worried (2.55, 95% CI 2.44 to 2.65, and 2.16, 95% CI 1.95 to 2.38, p=0.001).ConclusionsThis study has filled important gaps in the literature and highlighted the high prevalence of adults engaging in HISB for sexual health information. Of concern are the increased levels of anxiety and low accuracy of self-diagnoses associated with HISB. Strategies to direct patients to reputable and user-friendly health websites that mitigate anxiety and misinterpretation of online health information should be explored.
Diverging trends in US male-female condom use by STI risk factors: a nationally representative study
Authors: Copen Casey E , Dittus Patricia J , Leichliter Jami S , Kumar Sagar , Aral Sevgi O 
Published: November 2020

ObjectiveCondom use behaviours are proximal to recent STI increases in the USA, yet it remains unclear whether the use of condoms has changed over time among unmarried, non-cohabiting young men who have sex with women (MSW) and how this variability is influenced by STI risk factors.MethodsTo examine condom use over time among MSW aged 15–29, we used three cross-sectional surveys from the 2002, 2006–2010 and 2011–2017 National Survey of Family Growth. We estimated weighted percentages, adjusted prevalence ratios (APRs) and 95% confidence intervals (CI) to assess changes in condom use, stratified by whether MSW reported any STI risk factors in the past 12 months (ie, perceived partner non-monogamy, male-to-male sex, sex in exchange for money or drugs, sex partner who injects illicit drugs, or an HIV-positive sex partner).ResultsWe observed a divergence in trends in condom use at last sex between men aged 15 –29 with STI risk factors in the past 12 months and those without such history. We saw significant declines in condom use from 2002 to 2011–2017 among men with STI risk factors (APR=0.80, 95% CI 0.68 to 0.95), specifically among those aged 15–19 (APR=0.73, 95% CI 0.57 to 0.94) or non-Hispanic white (APR=0.71, 95% CI 0.54 to 0.93). In contrast, trends in condom use among men with no STI factors remained stable or increased. Across all time periods, the most prevalent STI risk factor reported was perception of a non-monogamous female partner (23.0%–26.9%). Post-hoc analyses examined whether condom use trends changed once this variable was removed from analyses, but no different patterns were observed.ConclusionsWhile STIs have been increasing, men aged 15–29 with STI risk factors reported a decline in condom use. Rising STI rates may be sensitive to behavioural shifts in condom use among young MSW with STI risk factors.
Ipilimumab and Radiation in Patients with High-risk Resected or Regionally Advanced Melanoma
Authors: Salama April K.S. , Palta Manisha , Rushing Christel N. , Selim M. Angelica , Linney Kristen N. , Czito Brian G. , Yoo David S. , Hanks Brent A. , Beasley Georgia M. , Mosca Paul J. , Dumbauld Chelsae , Steadman Katelyn N. , Yi John S. , Weinhold Kent J. , Tyler Douglas S. , Lee Walter T. , Brizel David M. 
Published: November 2020

AbstractPurpose:In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma.Patients and Methods:Twenty-four patients in two cohorts were enrolled and received ipilimumab at 3 mg/kg every 3 weeks for four doses in conjunction with radiation; median dose was 4,000 cGy (interquartile range, 3,550–4,800 cGy). Patients in cohort 1 were treated adjuvantly; patients in cohort 2 were treated either neoadjuvantly or as definitive therapy.Results:Adverse event profiles were consistent with those previously reported with checkpoint inhibition and radiation. For the neoadjuvant/definitive cohort, the objective response rate was 64% (80% confidence interval, 40%–83%), with 4 of 10 evaluable patients achieving a radiographic complete response. An additional 3 patients in this cohort had a partial response and went on to surgical resection. With 2 years of follow-up, the 6-, 12-, and 24-month relapse-free survival for the adjuvant cohort was 85%, 69%, and 62%, respectively. At 2 years, all patients in the neoadjuvant/definitive cohort and 10/13 patients in the adjuvant cohort were still alive. Correlative studies suggested that response in some patients were associated with specific CD4+ T-cell subsets.Conclusions:Overall, concurrent administration of ipilimumab and radiation was feasible, and resulted in a high response rate, converting some patients with unresectable disease into surgical candidates. Additional studies to investigate the combination of radiation and checkpoint inhibitor therapy are warranted.
A Novel Neoplastic Fusion Transcript, RAD51AP1-DYRK4, Confers Sensitivity to the MEK Inhibitor Trametinib in Aggressive Breast Cancers
Authors: Liu Chia-Chia , Veeraraghavan Jamunarani , Tan Ying , Kim Jin-Ah , Wang Xian , Loo Suet Kee , Lee Sanghoon , Hu Yiheng , Wang Xiao-Song 
Published: November 2020

Abstract

Purpose:
Luminal B breast tumors are more aggressive estrogen receptor–positive (ER+) breast cancers characterized by aggressive clinical behavior and a high risk of metastatic dissemination. The underlying pathologic molecular events remain poorly understood with a paucity of actionable genetic drivers, which hinders the development of new treatment strategies.

Experimental Design:
We performed large-scale RNA sequencing analysis to identify chimerical transcripts preferentially expressed in luminal B breast cancer. The lead candidate was validated by reverse transcription PCR in breast cancer tissues. The effects of inducible ectopic expression or genetic silencing were assessed by phenotypic assays such as MTS, transwell, and transendothelial migration assays, and by clonogenic assays to assess MEK inhibitor sensitivity. Subcellular fractionation, Western blots, and immunoprecipitation were performed to characterize the protein products and elucidate the engaged mechanisms.

Results:
Here we report a novel tumor-specific chimeric transcript RAD51AP1-DYRK4 preferentially expressed in luminal B tumors. Analysis of 200 ER+ breast tumors detected RAD51AP1-DYRK4 overexpression in 19 tumors (9.5%), which is markedly enriched in the luminal B tumors (17.5%). Ectopic expression of RAD51AP1-DYRK4, but not wild-type RAD51AP1, leads to marked activation of MEK/ERK signaling, and endows increased cell motility and transendothelial migration. More importantly, RAD51AP1-DYRK4 appears to endow increased sensitivity to the MEK inhibitor trametinib through attenuating compensatory activation of HER2/PI3K/AKT under MEK inhibition.

Conclusions:
This discovery sheds light on a new area of molecular pathobiology of luminal B tumors and implies potential new therapeutic opportunities for more aggressive breast tumors overexpressing this fusion.
Breast Tumor Kinase (Brk/PTK6) Mediates Advanced Cancer Phenotypes via SH2-Domain Dependent Activation of RhoA and Aryl Hydrocarbon Receptor (AhR) Signaling
Authors: Dwyer Amy R. , Kerkvliet Carlos Perez , Krutilina Raisa I. , Playa Hilaire C. , Parke Deanna N. , Thomas Warner A. , Smeester Branden A. , Moriarity Branden S. , Seagroves Tiffany N. , Lange Carol A. 
Published: November 2020

Abstract

Protein tyrosine kinase 6 (PTK6; also called Brk) is overexpressed in 86% of patients with breast cancer; high PTK6 expression predicts poor outcome. We reported PTK6 induction by HIF/GR complexes in response to either cellular or host stress. However, PTK6-driven signaling events in the context of triple-negative breast cancer (TNBC) remain undefined. In a mouse model of TNBC, manipulation of PTK6 levels (i.e., via knock-out or add-back) had little effect on primary tumor volume, but altered lung metastasis. To delineate the mechanisms of PTK6 downstream signaling, we created kinase-dead (KM) and kinase-intact domain structure mutants of PTK6 via in-frame deletions of the N-terminal SH3 or SH2 domains. While the PTK6 kinase domain contributed to soft-agar colony formation, PTK6 kinase activity was entirely dispensable for cell migration. Specifically, TNBC models expressing a PTK6 variant lacking the SH2 domain (SH2-del PTK6) were unresponsive to growth factor–stimulated cell motility relative to SH3-del, KM, or wild-type PTK6 controls. Reverse-phase protein array revealed that while intact PTK6 mediates spheroid formation via p38 MAPK signaling, the SH2 domain of PTK6 limits this biology, and instead mediates TNBC cell motility via activation of the RhoA and/or AhR signaling pathways. Inhibition of RhoA and/or AhR blocked TNBC cell migration as well as the branching/invasive morphology of PTK6+/AhR+ primary breast tumor tissue organoids. Inhibition of RhoA also enhanced paclitaxel cytotoxicity in TNBC cells, including in a taxane-refractory TNBC model.

Implications:
The SH2-domain of PTK6 is a potent effector of advanced cancer phenotypes in TNBC via RhoA and AhR, identified herein as novel therapeutic targets in PTK6+ breast tumors.
Machine Learned Cellular Phenotypes in Cardiomyopathy Predict Sudden Death
Authors: Rogers Albert J. , Selvalingam Anojan , Alhusseini Mahmood I. , Krummen David E. , Corrado Cesare , Abuzaid Firas , Baykaner Tina , Meyer Christian , Clopton Paul , Giles Wayne , Bailis Peter , Niederer Steven , Wang Paul J. , Rappel Wouter-Jan , Zaharia Matei , Narayan Sanjiv M. 
Published: November 2020

Rationale:
Susceptibility to VT/VF (ventricular tachycardia/fibrillation) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside.

Objective:
To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes.

Methods and Results:
We recorded 5706 ventricular MAPs in 42 patients with coronary artery disease and left ventricular ejection fraction ≤40% during steady-state pacing. Patients were randomly allocated to independent training and testing cohorts in a 70:30 ratio, repeated K=10-fold. Support vector machines and convolutional neural networks were trained to 2 end points: (1) sustained VT/VF or (2) mortality at 3 years. Support vector machines provided superior classification. For patient-level predictions, we computed personalized MAP scores as the proportion of MAP beats predicting each end point. Patient-level predictions in independent test cohorts yielded c-statistics of 0.90 for sustained VT/VF (95% CI, 0.76–1.00) and 0.91 for mortality (95% CI, 0.83–1.00) and were the most significant multivariate predictors. Interpreting trained support vector machine revealed MAP morphologies that, using in silico modeling, revealed higher L-type calcium current or sodium-calcium exchanger as predominant phenotypes for VT/VF.

Conclusions:
Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.
Thoughts on the Language of Sirach 36:1–22
Authors: Reymond Eric D. 
Published: November 2020

Abstract
Certain words in the prayer of Sir 36:1–22 that appear to be secondary exhibit nationalistic and eschatological tones that are otherwise alien to the book of Ben Sira. These elements likely reflect the interpretation and reading of the text in the course of its transmission in the first millennium CE. In its present form, therefore, the nationalistic/eschatological themes are accented in a way that might not have been the case in earlier versions.
The Hebrew of the Dead Sea Scrolls and the Tiberian Reading Tradition
Authors: Hornkohl Aaron D. 
Published: November 2020

Abstract
The most authentic portrait of Second Temple Hebrew is afforded by the Dead Sea Scrolls, especially by those texts actually composed in Hellenistic and Roman times. On salient linguistic points Dead Sea Scrolls Hebrew agrees with the vocalization of the Tiberian reading tradition against the testimony of the written, i.e., consonantal, tradition of Masoretic Classical Biblical Hebrew material. This article presents a case study. On the one hand, these Dead Sea-Tiberian vocalization affinities are evidence of the relatively late character of their respective linguistic traditions and of the secondary character of the developments in the Tiberian reading tradition vis-à-vis the classical biblical written tradition. On the other hand, these same affinities demonstrate that the Tiberian pronunciation tradition is plausibly regarded as one that crystallized in the Second Temple Period, rather than in Byzantine or medieval times. Lastly, since joint Dead Sea-Tiberian reading departures from the classical biblical consonantal tradition constitute a tiny minority of their relevant linguistic data, most of which are characterized by historical continuity and/or linguistic heterogeneity of comparable historical depth, it is clear that the Second Temple crystallization of Dead Sea Scrolls Hebrew and the Tiberian reading tradition in no way preclude their routine preservation of authentic Iron Age features.
Is There a Negative Polarity Item ‮דבר‬‎ in DSS Hebrew?
Authors: Moshavi Adina 
Published: November 2020

Abstract
A negative polarity item (NPI) is a word or expression that occurs grammatically in negative clauses and a variety of other types of clauses such as interrogatives and conditionals, but not in ordinary affirmative sentences. Examples from classical Biblical Hebrew include the pronoun ‮מאומה‬‎ “anything” and the semantically-bleached noun ‮דבר‬‎ “a thing,” which has been produced from the ordinary noun ‮דבר‬‎ “word, matter, action” by the process of grammaticalization. This paper examines the noun ‮דבר‬‎ in the non-biblical DSS with the purpose of determining whether it is used as there as an NPI, as in Biblical Hebrew, or as an ordinary semantically-bleached noun, as in Rabbinic Hebrew. The results show that the diachronic development of ‮דבר‬‎ in the DSS appears to be at an earlier stage than classical Biblical Hebrew, despite the later dating of the scrolls. This finding is explained as a special kind of pseudo-classicism.
Distribution of gamma-aminobutyric acid (GABA) in the central nervous system of the male mud crab, Scylla olivacea
Authors: Khornchatri Kanjana , Saetan Jirawat , Mukem Sirirak , Sobhon Prasert , Thongbuakaew Tipsuda 
Published: November 2020

Abstract
Gamma-aminobutyric acid (GABA) is a neurotransmitter that is widely spread in vertebrate and invertebrate nervous systems and modulates essential physiological roles. Previous studies have reported the distribution of several neurotransmitters throughout the central nervous system (CNS) of decapod crustaceans. However, the existence and distribution of GABA in the mud crab’s, Scylla olivacea, CNS has still not been reported. In this study, we investigated the distribution of GABA using immunohistochemistry. The result revealed that GABA immunoreactivity (-ir) was observed in neurons and fibres throughout the CNS, including the eyestalk, brain, and ventral nerve cord of S. olivacea. Therefore, the existence and extensive distribution pattern of GABA in the CNS of the male mud crab suggest its possible roles in feeding, locomotion, and also reproduction.
A new record of Porcellana persica Haig, 1966 (Decapoda, Anomura, Porcellanidae) from the Arabian Sea, India
Authors: Josileen Jose , Maheswarudu G. , Jinesh P. T. , Sreesanth L. , Ragesh N. , Lakshmi Pillai S. 
Published: November 2020

Abstract
Porcellana persica Haig, 1966 was collected from off the Kerala coast, Arabian Sea, India. This is the first record of both the genus and the species from Indian waters. The taxonomic characters are similar to the findings of Haig (1966), who described the species, and possibly this is the first detailed report on the species after her original description.
Innovation-Supporting Effect of Government Versus Private Venture Capital: Evidence from Chinese Listed Companies
Authors: Tao Xiaohui , Li Yang 
Published: November 2020

Abstract
Venture capital (VC) can promote the innovation of invested enterprises through financial support, social networking, and intellectual capital. Based on data of Chinese listed companies from 2003 to 2016, this study, firstly, compares the impact of government and private VC on enterprise innovation using Possion regression, and applies the ITCV method and Negative Binomial Regression for Robustness Examination, then, explores the relationship between their shareholding percentage and enterprise innovation with threshold test. The results show that: the performance of private VC is significantly positive and in line. With the increasing shareholding percentage of private VC, the innovation of invested enterprises increases. The overall performance of government VC, however, is not significant, and the shareholding percentage of government VC also has no significant impact on the innovation of invested companies. Additional testing revealed that a “threshold effect” however exists in the impact of the shareholding percentage of government VC on innovation: within a certain range, the higher the shareholding percentage, the more significant the impact on innovations becomes, but beyond that range, the percentage is inversely related to innovation.
Inscribed Spherical Agate Gemstone from the Anapa Region Revisited
Authors: Andreeva Eugenia N. 
Published: November 2020

Abstract
The paper focuses on one very unusual magical object originating from the territory of the Bosporan kingdom: an agate stone amulet with a rather extensive inscription found in the vicinity of ancient Gorgippia. The author summarizes the history of scholarly discussion on the subject and analyses Chr. Faraone’s “magical handbook” hypothesis putting forward some arguments against it. The paper not only revisits the reading of the text, but treats the artefact as a unity of the material object and the inscription there upon.
Non-Urban Societies of the Crimea and Their Response to Changes in the External World
Authors: Mordvintseva Valentina I. 
Published: November 2020

Abstract
The paper presents a comparative analysis of burial assemblages of ‘barbarian’ élites located on the territory of the Crimea between Chersonesos Taurica and the Bosporan kingdom dating from the 3rd century BC to the mid-3rd century AD. The main goal of the research is to define indications of self-identities of the Crimean non-urban societies represented by their élites and to outline their networking inside and outside the peninsula as well as their changes during four chronological periods. The research is based on the precondition that networking in the political sphere is closely connected to the exchange of symbols of power and status. In material culture, such symbols might be represented by the so-called ‘prestige objects’. Changes in the assortment of these items observed over a long time-span are helping to visualize the development of internal and external relationships of social élites.
Scythian Leather Quiver from Bulgakovo
Authors: Daragan Marina N. 
Published: November 2020

Abstract
What were items of Scythian archer’s equipment? What materials were used, and how were they produced? These issues remain currently practically unknown. Objects made from organic materials (wood, leather, and textile) in Scythian burials are lost or provide little information. For this reason almost nothing about Scythian archery equipment (bow and quiver) has been known for a long time. This article describes and analyzes the only well preserved quiver found in the Scythian burial of the 4th century BC in the North Pontic Region. The details of a leather quiver bag, a wooden stiffening plate, wooden painted arrows with bronze arrowheads have survived.