bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone Demethylase KDM4B Promotes DNA Damage by Activating Long Interspersed Nuclear Element-1
Authors: Xiang Ying , Yan Kai , Zheng Qian , Ke Haiqiang , Cheng Jie , Xiong Wenjun , Shi Xin , Wei Lei , Zhao Min , Yang Fei , Wang Ping , Lu Xing , Fu Li , Lu Xuemei , Li Feng 
Published: November 2018

Abstract

The histone demethylase KDM4B is frequently overexpressed in various cancer types, and previous studies have indicated that the primary oncogenic function of KDM4B is its ability to demethylate H3K9me3 in different tumors, resulting in altered gene expression and genome instability. A genome-wide analysis to evaluate the effect of KDM4B on the global or local H3K9me3 level has not been performed. In this study, we assess whole-genome H3K9me3 distribution in cancer cells and find that H3K9me3 is largely enriched in long interspersed nuclear element-1 (LINE-1). A significant proportion of KDM4B-dependent H3K9me3 was located in evolutionarily young LINE-1 elements, which likely retain retrotransposition activity. Ectopic expression of KDM4B promoted LINE-1 expression, while depletion of KDM4B reduced it. Furthermore, KDM4B overexpression enhanced LINE-1 retrotransposition efficacy, copy number, and associated DNA damage, presumably via the histone demethylase activity of KDM4B. Breast cancer cell lines expressing high levels of KDM4B also exhibited increased LINE-1 expression and copy number compared with other cell lines. Pharmacologic inhibition of KDM4B significantly reduced LINE-1 expression and DNA damage in breast cancer cells with excessive KDM4B. Our study not only identifies KDM4B as a novel regulator of LINE-1, but it also suggests an unexpected oncogenic role for KDM4B overexpression in tumorigenesis, providing clues for the development of new cancer prevention strategies and therapies.

Significance:
The histone demethylase KDM4B promotes tumorigenesis by inducing retrotransposition and DNA damage.
Receipt of Colonoscopy Following Diagnosis of Advanced Adenomas: An Analysis within Integrated Healthcare Delivery Systems
Authors: Chubak Jessica , McLerran Dale , Zheng Yingye , Singal Amit G. , Corley Douglas A. , Doria-Rose V. Paul , Doubeni Chyke A. , Kamineni Aruna , Haas Jennifer S. , Halm Ethan A. , Skinner Celette Sugg , Zauber Ann G. , Wernli Karen J. , Beaber Elisabeth F. 
Published: November 2018

Abstract

Background:
To reduce colorectal cancer incidence and mortality, experts recommend surveillance colonoscopy 3 years after advanced adenoma removal. Little is known about adherence to that interval.

Methods:
We describe patterns of and factors associated with subsequent colonoscopy among persons with ≥3 adenomas and/or ≥1 adenoma with villous/tubulovillous histology in four U.S. integrated healthcare delivery systems. We report Kaplan–Meier estimators of the cumulative percentage of patients undergoing colonoscopy 6 months to 3.5 years after an index colonoscopy with high-risk findings. Combining data from three healthcare systems, we used multivariable logistic regression with inverse probability of censoring weights to estimate ORs and 95% confidence intervals (CI) for associations between patient characteristics and receipt of subsequent colonoscopy.

Results:
Among 6,909 persons with advanced adenomas, the percent receiving a subsequent colonoscopy 6 months to 3.5 years later ranged from 18.3% (95% CI: 11.7%–27.8%) to 59.5% (95% CI: 53.8%–65.2%) across healthcare systems. Differences remained significant in the multivariable model. Patients with ≥3 adenomas were more likely than those with 1 to 2 villous/tubulovillous adenomas to undergo subsequent colonoscopy. Subsequent colonoscopy was also more common for patients ages 60–74 and less common for patients ages 80 to 89 compared with those ages 50 to 54 years at their index colonoscopy. Sex, race/ethnicity, and comorbidity index score were generally not associated with subsequent colonoscopy receipt.

Conclusions:
Colonoscopy within the recommended interval following advanced adenoma was underutilized and varied by healthcare system, age, and number of adenomas.

Impact:
Strategies to improve adherence to surveillance colonoscopy following advanced adenomas are needed.
ВИВЧЕННЯ ПРОТИЗАПАЛЬНОЇ АКТИВНОСТІ СУХОГО ЕКСТРАКТУ З ЛИСТЯ САЛАТУ ПОСІВНОГО
Authors: Puda V. P. , Fira L. S. , Lykhatskyi P. H. 
Published: November 2018

Вступ. Проблема фармакологічної корекції запалення, як і раніше, залишається актуальною, оскільки сучасна медицина повністю її не вирішила. Одним із перспективних напрямів створення безпечних та ефективних протизапальних препаратів є фітотерапія. В останні роки підвищився інтерес до препаратів рослинного походження.
Мета дослідження – вивчити протизапальну активність сухого екстракту з листя салату посівного в експерименті з модельованим карагеніновим набряком лапи щурів.
Методи дослідження. При визначенні протизапальної активності екстракту з листя салату посівного використовували безпородних білих щурів-самців масою 180–200 г. Індукцію гострого асептичного запалення проводили шляхом субплантарної ін’єкції 0,1 мл 1 % розчину карагеніну. Досліджуваний зразок екстракту в дозі 100 мг/кг маси тіла вводили піддослідним щурам внутрішньошлунково у профілактичному режимі одноразово за 1 год до індукції запалення. Через 1, 3, 6 та 24 год вимірювали об’єм здорової та ураженої кінцівок за допомогою механічного онкометра. Антиексудативну активність екстракту визначали за ступенем зменшення набряку в піддослідних тварин порівняно з контрольними та виражали у відсотках. Як препарат порівняння використовували диклофенак натрію в дозі 8 мг/кг.
Результати й обговорення. Встановлено, що у групі тварин, які отримували екстракт з листя салату посівного, максимальний позитивний вплив на розвиток набряку спостерігали через 3 год від початку запалення (31,22 %), і тривав він до кінця експерименту. Через 24 год від початку розвитку запалення ефект від застосування екстракту був дещо нижчим. Але найменш виражений його вплив на розвиток запалення відзначали через 1 год дослідження. Аналогічний вплив мав диклофенак натрію, щоправда значний ефект від його застосування проявився вже через 1 год від початку експерименту.
Висновок. Доведено виразну протизапальну активність сухого екстракту з листя салату посівного, який найбільш активно пригнічує розвиток набряку лапи щурів через 1 год запалення.
A General Method for Estimating Bulk 2D Projections of Ice Particle Shape: Theory and Applications
Authors: Dunnavan Edwin L. , Jiang Zhiyuan 
Published: November 2018

Abstract
The orientation of falling ice particles directly influences estimates of microphysical and radiative bulk quantities as well as in situ retrievals of size, shape, and mass. However, retrieval efforts and bulk calculations often incorporate very basic orientations or ignore these effects altogether. To address this deficiency, this study develops a general method for projecting bulk distributions of particle shape for arbitrary orientations. The Amoroso distribution provides the most general bulk aspect ratio distribution for gamma-distributed particle axis lengths. The parameters that govern the behavior of this aspect ratio distribution depend on the assumed relationship between mass, maximum dimension, and aspect ratio. Individual spheroidal geometry allows for eccentricity quantities to linearly map onto ellipse analogs, whereas aspect ratio quantities map nonlinearly. For particles viewed from their side, this analytic distinction leads to substantially larger errors in projected aspect ratio than for projected eccentricity. Distribution transformations using these mapping equations and numerical integration of projection kernels show that both truncation of size distributions and changes in Gaussian dispersion can alter the modality and shape of projection distributions. As a result, the projection process can more than triple the relative entropy between the spheroidal and projection distributions for commonly assumed model and orientation parameters. This shape uncertainty is maximized for distributions of highly eccentric particles and for particles like aggregates that are thought to fall with large canting-angle deviations. As a result, the methods used to report projected aspect ratios and the corresponding values should be questioned.
Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion
Authors: Stoffel Elena M. , McKernin Shannon E. , Brand Randall , Canto Marcia , Goggins Michael , Moravek Cassadie , Nagarajan Arun , Petersen Gloria M. , Simeone Diane M. , Yurgelun Matthew , Khorana Alok A. 
Published: November 2018

Purpose An ASCO provisional clinical opinion (PCO) offers timely clinical direction to ASCO’s membership and other health care providers. This PCO addresses identification and management of patients and family members with possible predisposition to pancreatic adenocarcinoma. Methods ASCO convened an Expert Panel and conducted a systematic review of the literature published from January 1998 to June 2018. Results of the databases searched were supplemented with hand searching of the bibliographies of systematic reviews and selected seminal articles and contributions from Expert Panel members’ curated files. Provisional Clinical Opinion All patients diagnosed with pancreatic adenocarcinoma should undergo assessment of risk for hereditary syndromes known to be associated with an increased risk for pancreatic adenocarcinoma. Assessment of risk should include a comprehensive review of family history of cancer. Individuals with a family history of pancreatic cancer affecting two first-degree relatives meet criteria for familial pancreatic cancer (FPC). Individuals (cancer affected or unaffected) with a family history of pancreatic cancer meeting criteria for FPC, those with three or more diagnoses of pancreatic cancer in same side of the family, and individuals meeting criteria for other genetic syndromes associated with increased risk for pancreatic cancer have an increased risk for pancreatic cancer and are candidates for genetic testing. Germline genetic testing for cancer susceptibility may be discussed with individuals diagnosed with pancreatic cancer, even if family history is unremarkable. Benefits and limitations of pancreatic cancer screening should be discussed with individuals whose family history meets criteria for FPC and/or genetic susceptibility to pancreatic cancer. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .
Neuromuscular degeneration and locomotor deficit in a Drosophila model of mucopolysaccharidosis VII is attenuated by treatment with resveratrol
Authors: Bar Sudipta , Prasad Mohit , Datta Rupak 
Published: November 2018

ABSTRACT
Mucopolysaccharidosis VII (MPS VII) is a recessively inherited lysosomal storage disorder caused by β-glucuronidase enzyme deficiency. The disease is characterized by widespread accumulation of non-degraded or partially degraded glycosaminoglycans, leading to cellular and multiple tissue dysfunctions. The patients exhibit diverse clinical symptoms, and eventually succumb to premature death. The only possible remedy is the recently approved enzyme replacement therapy, which is an expensive, invasive and lifelong treatment procedure. Small-molecule therapeutics for MPS VII have so far remained elusive primarily due to lack of molecular insights into the disease pathogenesis and unavailability of a suitable animal model that can be used for rapid drug screening. To address these issues, we developed a Drosophila model of MPS VII by knocking out the CG2135 gene, the fly β-glucuronidase orthologue. The CG2135−/− fly recapitulated cardinal features of MPS VII, such as reduced lifespan, progressive motor impairment and neuropathological abnormalities. Loss of dopaminergic neurons and muscle degeneration due to extensive apoptosis was implicated as the basis of locomotor deficit in this fly. Such hitherto unknown mechanistic links have considerably advanced our understanding of the MPS VII pathophysiology and warrant leveraging this genetically tractable model for deeper enquiry about the disease progression. We were also prompted to test whether phenotypic abnormalities in the CG2135−/− fly can be attenuated by resveratrol, a natural polyphenol with potential health benefits. Indeed, resveratrol treatment significantly ameliorated neuromuscular pathology and restored normal motor function in the CG2135−/− fly. This intriguing finding merits further preclinical studies for developing an alternative therapy for MPS VII.
This article has an associated First Person interview with the first author of the paper.
Electrolytic Cross-Coupling of Arenediazonium Salts and Heteroarenes
Authors: Hata Dai , Tobisu Mamoru , Amaya Toru 
Published: November 2018

Abstract
The cathodic reduction-induced cross-coupling of arenediazonium salts and heteroarenes was employed to prepare heterobiaryl derivatives. This reaction is attractive because it allows the direct arylation of an aromatic C-H bond in a heteroarene derivative. A radical chain mechanism appears to be involved.
Impact of modern radiotherapy techniques on survival outcomes for unselected patients with large volume non-small cell lung cancer
Authors: Shrimali Raj Kumar , Chakraborty Santam , Prasath Sriram , Arun B , Chatterjee Sanjoy 
Published: November 2018

Objective:
Intensity modulated radiotherapy (IMRT) is used, where necessary, for bulky or complex-shaped, locally advanced, non-small cell lung cancer (NSCLC). We evaluate our real-world experience with radical radiotherapy including concurrent chemoradiation (CCRT), and analyse the impact of IMRT on survival outcomes in patients with larger volume disease.

Methods:
All patients treated between May 2011 and December 2017 were included. Analyses were conducted for factors affecting survival, including large volume disease that was defined as planning target volume (PTV) &gt; 500 cc.

Results:
In 184 patients with large volume disease, the median overall survival was 19.2 months, compared to 22 months seen with the overall cohort of 251 patients who received radical radiotherapy. PTV and using CCRT were significant predictors for survival. IMRT was used in 93 (50.5%) of 184 patients with large PTV. The patients treated using IMRT had significantly larger disease volume (median PTV = 859 vs 716 cc; p-value = 0.009) and more advanced stage (proportion of Stage IIIB: 56 vs 29%; p-value = 0.003) compared to patients treated with three-dimensional conformal radiotherapy. Yet, the outcomes with IMRT were non-inferior to those treated with 3DCRT. CCRT was used in 103 (56%) patients with large volume disease and resulted in a significantly better median survival of 24.9 months. The proportional benefit from CCRT was also greater than in the overall cohort.

Conclusion:
Despite being used for larger volume and more advanced NSCLC, inverse-planned IMRT resulted in non-inferior survival.

Advances in knowledge:
IMRT enables the safe use of curative CCRT for large-volume, locally-advanced NSCLC.
gganatogram: An R package for modular visualisation of anatograms and tissues based on ggplot2
Authors: Maag Jesper L.V. 
Published: November 2018

Displaying data onto anatomical structures is a convenient technique to quickly observe tissue related information. However, drawing tissues is a complex task that requires both expertise in anatomy and the arts. While web based applications exist for displaying gene expression on anatograms, other non-genetic disciplines lack similar tools. Moreover, web based tools often lack the modularity associated with packages in programming languages, such as R.Here I present gganatogram, an R package used to plot modular species anatograms based on a combination of the graphical grammar of ggplot2 and the publicly available anatograms from the Expression Atlas. This combination allows for quick and easy, modular, and reproducible generation of anatograms. Using only one command and a data frame with tissue name, group, colour, and value, this tool enables the user to visualise specific human and mouse tissues with desired colours, grouped by a variable, or displaying a desired value, such as gene-expression, pharmacokinetics, or bacterial load across selected tissues. gganatogram consists of 5 highly annotated organisms, male/female human/mouse, and a cell anatogram. It further consists of 24 other less annotated organisms from the animal and plant kingdom. I hope that this tool will be useful by the wider community in biological sciences. Community members are welcome to submit additional anatograms, which can be incorporated into the package.A stable version gganatogram has been deposited toneuroconductor, and a development version can be found on github/jespermaag/gganatogram. An interactive shiny app of gganatogram can be found on https://jespermaag.shinyapps.io/gganatogram/, which allows for non-R users to create anatograms.
The experiences of family caregivers providing palliative cancer care in Thailand
Authors: Wannapornsiri Chommanard 
Published: November 2018

Background: Family caregivers have a significant role in Thai healthcare, taking on responsibilities of health professionals. The purpose of this research was to explore Thai family caregivers' experiences of providing palliative cancer care. Methods: This qualitative study took a phenomenological approach. In-depth interviews were conducted with 14 family caregivers aged 33–72 years in a regional hospital in the north of Thailand. The data was analysed using Colaizzi's phenomenological approach. Rigour was established by following Lincoln and Guba's guidelines for qualitative research. Findings: The experiences of Thai family caregivers providing palliative cancer care could be categorised into four themes: caring as a team; caring as supportive care; taking care to keep patients happy; and caring for the self while looking after a relative. Conclusion: Health professionals can support family caregivers to deliver the best care for cancer patients and to help them decrease their stress. This study discusses ways how this may be done.
Sepsis in adults: Recognition and treatment in clinical guidelines
Authors: Sevillano-Barbero Manuel 
Published: November 2018

Sepsis is a potentially fatal condition, causing approximately five deaths every hour in the UK. However, new research is being published and guidelines are continually being updated—making it vital for general practice nurses to stay up-to-date with the latest developments Sepsis is a life-threatening condition. It is responsible for the majority of deaths in intensive care units worldwide, however, its pathophysiology is still not well understood. Over the past 2 decades, sepsis has been defined several times; the most recent was the Third International Consensus Definition for Sepsis and Septic Shock in 2016. It is becoming a ‘hot topic’ in healthcare—different organisations, such as the UK Sepsis Trust, are working towards raising awareness of sepsis and the importance of early recognition in improving outcomes. This subsequently led to the publication of the National Institute for Health and Care Excellence clinical guidelines for sepsis in 2016, updated in 2017. This article will explore the history of the definition of sepsis; the most updated protocols for early recognition and treatment; and the Sepsis Six. It will conclude with a list of relevant online resources available, in order to aid clinicians in their daily practice.
Family violence risk, migration status and ‘vulnerability’: hearing the voices of immigrant women
Authors: Maher JaneMaree , Segrave Marie 
Published: November 2018

In this paper, we draw on accounts of family violence risk offered by women from culturally and linguistically diverse (CALD) communities living in Victoria Australia, and examine how women’s migration and experiences of difference impact on the risks they face from family violence. Women in refugee and immigrant communities are often understood as experiencing additional barriers and vulnerabilities when they face family violence; implicitly creating a deficit model of vulnerability attached to women’s intersectional marginalization particularly in terms of migration and service regimes.
Yet when we focus on women’s own accounts of risk and safety, we argue that the ‘vulnerabilities’ these women experience are in fact predominantly created by service and legislative regimes that operate in terms of gender and migration. Rather than assuming that such vulnerabilities are inherent for women from CALD communities, we need to better recognise women’s own assessments of risk and their searches for safety. Service and legislative responses that can support rather than inhibit women’s efforts to secure their own safety are critical.
Misogyny online: extending the boundaries of hate crime
Authors: Lewis Ruth , Rowe Michael , Wiper Clare 
Published: November 2018

GBV has generated interventions from activists and scholars throughout Europe and beyond. As a newly emerging form of GBV, online abuse has to date generated fewer interventions and conceptual discussions. The article argues that this is partly because this is an emerging issue but also because it poses distinct challenges because it has no national boundaries and because it challenges traditional notions of public and private space.
Drawing on survey and interview data with women abused online further to participation in feminist activism, the paper develops debates about responses to misogynistic abuse. The paper considers whether online misogynistic abuse is a form of hate crime. Using existing literature, three dimensions of hate crime are identified: the nature of motivation, exclusionary intent, and spatial context. In respect of each, the findings presented here suggest that this abuse could be a form of hate crime. There are difficulties in respect of each, and anomalies are identified. However, these are of no greater magnitude than those which apply more widely to other forms of hate crime.
Interplay between Rapid Diagnostic Tests and Antimicrobial Stewardship Programs among Patients with Bloodstream and Other Severe Infections
Authors: Beganovic Maya , McCreary Erin K , Mahoney Monica V , Dionne Brandon , Green Daniel A , Timbrook Tristan T 
Published: November 2018

Abstract

Background
Antimicrobial stewardship programs (ASPs) aim to provide optimal antimicrobial therapy to patients quickly to improve the likelihood of overcoming infection while reducing the risk of adverse effects. Rapid diagnostic tests (RDTs) for infectious diseases have become an integral tool for ASPs to achieve these aims.

Content
This review explored the demonstrated clinical value of longer-standing technologies and implications of newer RDTs from an antimicrobial stewardship perspective. Based on available literature, the focus was on the use of RDTs in bloodstream infections (BSIs), particularly those that perform organism identification and genotypic resistance detection, phenotypic susceptibility testing, and direct specimen testing. Clinical implications of rapid testing among respiratory, central nervous system, and gastrointestinal infections are also reviewed.

Summary
Coupling RDTs with ASPs facilitates the appropriate and timely use of test results, translating into improved patient outcomes through optimization of antimicrobial use. These benefits are best demonstrated in the use of RDT in BSIs. Rapid phenotypic susceptibility testing offers the potential for early pharmacokinetic/pharmacodynamic optimization, and direct specimen testing on blood may allow ASPs to initiate appropriate therapy and/or tailor empiric therapy even sooner than other RDTs. RDTs for respiratory, central nervous system, and gastrointestinal illnesses have also shown significant promise, although more outcome studies are needed to evaluate their full impact.