bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive OFF-ON type alkylating agents for higher-ordered structures of nucleic acids
Authors: Onizuka Kazumitsu , Hazemi Madoka E , Sato Norihiro , Tsuji Gen-ichiro , Ishikawa Shunya , Ozawa Mamiko , Tanno Kousuke , Yamada Ken , Nagatsugi Fumi 
Published: May 2019

Abstract
Higher-ordered structure motifs of nucleic acids, such as the G-quadruplex (G-4), mismatched and bulge structures, are significant research targets because these structures are involved in genetic control and diseases. Selective alkylation of these higher-order structures is challenging due to the chemical instability of the alkylating agent and side-reactions with the single- or double-strand DNA and RNA. We now report the reactive OFF-ON type alkylating agents, vinyl-quinazolinone (VQ) precursors with a sulfoxide, thiophenyl or thiomethyl group for the OFF-ON control of the vinyl reactivity. The stable VQ precursors conjugated with aminoacridine, which bind to the G-4 DNA, selectively reacted with a T base on the G-4 DNA in contrast to the single- and double-strand DNA. Additionally, the VQ precursor reacted with the T or U base in the AP-site, G-4 RNA and T-T mismatch structures. These VQ precursors would be a new candidate for the T or U specific alkylation in the higher-ordered structures of nucleic acids.
UK safety-engineered device use: changes since the 2013 sharps regulations
Authors: Grimmond T 
Published: May 2019

Abstract

Background
The 2013 UK sharps safety regulations require healthcare facilities to use safety-engineered devices (SEDs) to protect staff. The recent increase in UK-reported occupational exposures could indicate increased reporting or increased exposures from suboptimal SED use.

Aims
To ascertain SED use through examination of sharps container contents in a sample of UK hospitals.

Methods
Reusable sharps containers (RSCs) were selected from seven UK hospitals in 2013 and seven different hospitals in 2016. At licensed processing facilities, the operator, wearing protective apparel, decanted RSCs, separated hollow-bore needles (HBNs) from other sharps and enumerated HBNs into capped/uncapped non-SEDs, activated/non-activated/tampered SEDs, and blunt draw-up SEDs. Probability, risk ratios (RRs) and 95% confidence limits (95% CLs) were calculated using WinPepi v2.78.

Results
In 2013 and 2016, respectively, 2545 HBNs were categorized from 22 RSCs versus 2959 HBNs from 33 RSCs; 70% of HBNs were SEDs versus 93% (P < 0.001; RR 1.33; CL 1.30–1.37); 32% of activatable HBNs were not activated versus 22% (<0.001; 0.67; 0.60–0.76); 41% of HBNs were discarded ‘sharp’ versus 20% (<0.001; 0.48; 0.44–0.52); 25% of HBNs were uncapped needles versus 6% (<0.001; 0.22; 0.19–0.26); 5% of HBNs were capped needles versus 1% (P > 0.05); and 1% of SEDs were tampered with in both years (P > 0.05). Hospital practices varied widely.

Conclusions
SED use and activation have increased significantly since 2013. Of concern is that in 2016, 22% of SEDs were non-activated and 20% of sharps were discarded ‘sharp’. Increased training in SED handling, assiduous adherence to safe sharps work practices and a higher level of individual safety-ownership are indicated.
Impact of Levofloxacin for the Prophylaxis of Bloodstream Infection on the Gut Microbiome in Patients With Hematologic Malignancy
Authors: Ziegler Matthew , Han Jennifer H , Landsburg Daniel , Pegues David , Reesey Emily , Gilmar Cheryl , Gorman Theresa , Bink Kristen , Moore Amy , Kelly Brendan J ,   CDC Prevention Epicenters Program
Published: May 2019

Abstract

Background
We evaluated the differential impact of levofloxacin administered for the prophylaxis of bloodstream infections compared with broad-spectrum beta-lactam (BSBL) antibiotics used for the treatment of neutropenic fever on the gut microbiome in patients with hematologic malignancy.

Methods
Stool specimens were collected from patients admitted for chemotherapy or stem cell transplant in the setting of the evaluation of diarrhea from February 2017 until November 2017. Microbiome characteristics were compared among those exposed to levofloxacin prophylaxis vs those who received BSBL antibiotics.

Results
Sixty patients were included, most with acute myeloid leukemia (42%) or multiple myeloma (37%). The gut microbiome of patients with BSBL exposure had significantly reduced Shannon’s alpha diversity compared with those without (median [interquartile range {IQR}], 3.28 [1.73 to 3.71] vs 3.73 [3.14 to 4.31]; P = .01). However, those with levofloxacin exposure had increased alpha diversity compared with those without (median [IQR], 3.83 [3.32 to 4.36] vs 3.32 [2.35 to 4.02]; P = .03). Levofloxacin exposure was also associated with a trend toward lower risk of dominance of non-Bacteroidetes genera compared with those without levofloxacin exposure (3 [14%] vs 15 [38%]; P = .051).

Conclusions
The impact of antibiotics on the gut microbiome varies by class, and levofloxacin may disrupt the gut microbiome less than BSBLs in this patient population.
Higher Bank Capital Requirements and Mortgage Pricing: Evidence from the Counter-Cyclical Capital Buffer*
Authors: Basten Christoph 
Published: May 2019

Abstract
We identify the effects of the Basel III macroprudential tool Counter-Cyclical Capital Buffer on mortgage lending. Using the first dataset on responses from multiple banks to each household, we find no evidence of explicit rationing. But as the CCyB applied only to mortgages, banks with higher mortgage specialization or lower capital cushions raise prices by an extra eight basis points. Bank level data then show that this allows them to slow their mortgage growth and rebuild capital cushions. While market-wide mortgage growth did not slow down significantly, the composition of mortgage suppliers thus moved to previously less exposed banks.
Women’s Leadership in Oman: An Intersectional and Transnational Perspective
Authors: Hallward Maia Carter , Bekdash Muellers Hania 
Published: May 2019

AbstractWomen’s leadership in the Middle East is typically explored along themes related to Islam and social norms that overlook countries’ complex transnational histories. Taking Oman as a case study, we employ the feminist lens of intersectionality to analyze how class, race, and generation differentiate women’s opportunities for leadership. Using interviews conducted with thirty-two women in Oman who have achieved success in variety of fields, this article finds that contrary to expectations in the literature, Islam does not appear to serve as an overarching challenge. Instead, women emphasize factors such as family connections, culture, and domestic responsibilities in shaping positionalities.
The ‘Rainbow Alliance’ or the Focus Group? Sexuality and Race in the Labour Party’s Electoral Strategy, 1985–7
Authors: Murphy C 
Published: May 2019

Abstract
In the 1980s, Labour struggled to respond to a hostile political context during a protracted period of opposition. Diverse figures claimed that the Left was suffering from a structural decline in a supposed ‘traditional working class’ voting base: contentions which only became more influential after the 1983 electoral catastrophe. Competing solutions were proffered—including building a ‘rainbow alliance’ informed by equalities politics, or appealing to a southern ‘new working class’. The latter interpretation gained greater influence on Neil Kinnock’s leadership. To fully understand why one triumphed over the other in the evolving strategy of the Labour Party, we should in part trace discourses, including contemporary ‘loony Left’ scandals. However, we must also recognize the importance of ‘epistemological practice’, which was crucial in shaping how political actors acquired knowledge and forged interpretations of the electorate. Focusing on the evolution of the epistemological practice of Kinnock’s leadership team—in particular, their increasing reliance on qualitative opinion research techniques like focus groups to supplement quantitative attitudinal polling—helps explain why they became convinced that recent controversies involving race and sexuality were having acutely negative consequences for Labour nationally. This furnishes us with a deeper understanding of the relationship between grassroots and national Left-wing politics in the 1980s. It also illuminates Labour’s cautious approach to equalities politics into the 1990s.
Factors Associated With Quality of Death in Korean ICUs As Perceived by Medical Staff: A Multicenter Cross-Sectional Survey
Authors: Cho Jun Yeun , Park Ju-Hee , Kim Junghyun , Lee Jinwoo , Park Jong Sun , Cho Young-Jae , Yoon Ho Il , Lee Sang-Min , Lee Jae-Ho , Lee Choon-Taek , Lee Yeon Joo 
Published: May 2019

Objectives:
Facilitating a high quality of death is an important aspect of comfort care for patients in ICUs. The quality of death in ICUs has been rarely reported in Asian countries. Although Korea is currently in the early stage after the implementation of the “well-dying” law, this seems to have a considerable effect on practice. In this study, we aimed to understand the status of quality of death in Korean ICUs as perceived by medical staff, and to elucidate factors affecting patient quality of death.

Design:
A multicenter cross-sectional survey study.

Setting:
Medical ICUs of two tertiary-care teaching hospitals and two secondary-care hospitals.

Patients:
Deceased patients from June 2016 to May 2017.

Interventions:
Relevant medical staff were asked to complete a translated Quality of Dying and Death questionnaire within 48 hours after a patient’s death. A higher Quality of Dying and Death score (ranged from 0 to 100) corresponded to a better quality of death.

Measurements and Main Results:
A total of 416 completed questionnaires were obtained from 177 medical staff (66 doctors and 111 nurses) of 255 patients. All 20 items of the Quality of Dying and Death received low scores. Quality of death perceived by nurses was better than that perceived by doctors (33.1 ± 18.4 vs 29.7 ± 15.3; p = 0.042). Performing cardiopulmonary resuscitation and using inotropes within 24 hours before death were associated with poorer quality of death, whereas using analgesics was associated with better quality of death.

Conclusions:
The quality of death of patients in Korean ICUs was considerably poorer than reported in other countries. Provision of appropriate comfort care, avoidance of unnecessary life-sustaining care, and permission for more frequent visits from patients’ families may correspond to better quality of death in Korean medical ICUs. It is also expected that the new legislation would positively affect the quality of death in Korean ICUs.
Transforming Veterans Health Administration Mental Health Clinician Education and Practices: 20 Years of Educational Initiatives by a Center of Excellence
Authors: Bryan Jennifer L. , Kauth Michael R. , Asghar-Ali Ali A. 
Published: May 2019

Abstract:
Twenty years ago, the US Congress articulated a need to decrease the time it takes clinical best practices to move from the literature to daily clinical practice. The Veterans Affairs South Central Mental Illness Research, Education, and Clinical Center was one of several centers of excellence established to address this need. It is also unique in that it focuses on rural and underserved veterans. This article summarizes the education accomplishments of the South Central Mental Illness Research, Education, and Clinical Center thus far in providing educational resources and trainings to frontline Veterans Affairs mental health staff with the goal of bringing best practices to routine clinical care, thus improving mental health services. We describe the use of implementation science to support dissemination of information, such as the monthly mental health grand rounds, especially for rural staff to receive continuing education, and the adoption of evidence-based psychotherapy trainings. The Clinical Educator Grants program allows clinicians to share their clinical expertise through development of practical tools for practice gaps they identify. We describe some future directions to meet the evolving needs of Veterans Affairs and community clinicians to provide the best possible care to Veterans. Take-away messages are that, for trainings to be successful, an implementation plan is critical and that an effective educational program requires funding and leadership commitment.
Personal Commitment Statements: Encouraging the Clinical Application of Continuing Professional Development Events for Health Practitioners in Low- and Middle-Income Countries
Authors: Bornman Juan , Louw Brenda 
Published: May 2019

Introduction:
Statements of commitment to change are commonly used to evaluate continuing medical education. However, this approach is new to evaluating the continuing professional development (CPD) of other health care practitioners such as audiology, speech-language therapy, occupational therapy, and physiotherapy in low- and middle-income countries. This study explored the use of Personal Commitment (to change) Statements (PCSs) as an evaluation tool of continuing education for health professionals in low- and middle-income countries, and its impact on the integration of new knowledge and skills with previous knowledge and clinical practice.

Methods:
PCSs were used in a case study conducted at a 1-day interprofessional CPD event held for health practitioners in South Africa. A qualitative thematic analysis was made of these PCSs, and results were synthesized into main themes.

Results:
Thirty-two participants turned in a PCS at the end of the CPD event with a total of 71 text statements. Three main domains were identified: (1) applying new knowledge in practice (61.97%); (2) increasing training-related content knowledge (21.12%); and (3) sharing information, skill, and resources (16.9%).

Discussion:
This study demonstrated that personal commitment statements can be used to describe the outcomes of CPD events for audiologists, speech-language, occupational, and physiotherapists. Participants engaged in reflection generated by the personal commitment statement, which contained no guiding statements, yet elicited responses showing that participants were more aware of the assessment tools and how they could use them in practice. Further study is warranted into the process and the role of follow-up regarding health practitioners' commitment to change in clinical practice.
Shared Reading Practices and Early Literacy Promotion in the First Year of Life
Authors: Sinclair Elizabeth M. , McCleery Ellen J. , Koepsell Lorraine , Zuckerman Katharine E. , Stevenson Ellen B. 
Published: May 2019

ABSTRACT:
Limited research exists on family reading practices, the impact of counseling, and book distribution in the first 6 months of life, despite recommendations from the American Academy of Pediatrics and Reach Out and Read promoting shared reading from birth.

Objective:
To describe infant home reading trajectories and environments in the first year and to assess whether receiving books starting in the newborn period, compared with starting at 6 months, alters these trajectories.

Methods:
Two study groups were enrolled in a quasi-experimental sequential cohort study; both groups received shared reading counseling starting in the newborn period and completed surveys throughout the first year. The Standard group received books starting at 6 months, whereas the Early Books group received books starting at 2 weeks. Reading trajectories were assessed both overall and between the study groups.

Results:
At the 2-week visit, less than half of families in each group had started shared reading with their infant, which rose to >97% by 12 months. Approximately two-thirds of families owned >10 children's books at 2 weeks, which increased to >80% at 12 months. Incorporating shared reading into bedtime routines also increased during the first year. Early versus standard book distribution did not alter these trajectories.

Conclusion:
Over the first year of life, families almost universally initiated shared reading and increased the number of books in the home. Reading habits established during this time were maintained in both groups. Literacy promotion beginning at the earliest well-child visits may help establish routines that will persist throughout childhood.
Residual hepatitis C virus in peripheral blood mononuclear cell as a risk factor for hepatocellular carcinoma after achieving a sustained virological response: a dogma or fiction
Authors: Hanafy Amr S. , Seleem Waseem M. , Basha Mohammad A.A. , Marei Ayman M. 
Published: May 2019

Background
Clinical worsening after achieving a sustained virological response (SVR) needs to be clarified and explained. Persistence of hepatitis C virus (HCV) core antigen interacts with the host proteins to interfere with signaling pathways and increases the susceptibility to hepatic carcinogenesis.

Objective
This study aimed to investigate the risk factors that increase the progression of liver disease and hepatocellular carcinoma in a subgroup of HCV patients who achieved a SVR.

Patients and methods
Eighty-nine HCV patients with hepatic decompensation were selected 8.2 ± 1.8 months after achieving SVR24. HCV core antigen and HCV RNA were detected in peripheral blood mononuclear cells. Matched control (n = 100) and training (n = 200) groups were recruited.

Results
Eighty-five patients showed a progression of Child–Turcotte–Pugh and model for end-stage liver disease scores, with positive RNA in peripheral blood mononuclear cell (357.4 ± 42.1 IU/million cell) and positive hepatitis C virus core antigen (n = 73); four patients were excluded. Susceptibility to decompensation and hepatocellular carcinoma after direct-acting antiviral drugs increased with age [odds ratio (OD) = 1.87], and was associated with male sex (OD = 1.65), diabetes (OD = 3.68), thrombocytopenia (OD = 2.44), pretreatment Alfa-fetoprotein (OD = 3.41), and occult HCV (OD = 4.1).

Conclusion
Clinical deterioration after SVR could be explained by occult HCV mainly in older male patients with diabetes and thrombocytopenia.
Determination of Serum Infliximab Concentration by Point‐of‐care Devices in Children With Inflammatory Bowel Disease
Authors: Curci Debora , Lucafò Marianna , Cifù Adriana , Bramuzzo Matteo , Martelossi Stefano , Favretto Diego , De Pellegrin Francesca , Fabris Martina , Vascotto Fulvia , Naviglio Samuele , Ventura Alessandro , Stocco Gabriele , Decorti Giuliana 
Published: May 2019

ABSTRACTObjectives:Therapeutic drug monitoring is becoming increasingly important in clinical decision‐making in children with inflammatory bowel disease (IBD). However, enzyme‐linked immunosorbent assay (ELISA) assays do not allow results to be provided in real‐time. We sought to compare 2 point‐of‐care (POC) devices for quantification of serum infliximab concentration with 2 validated ELISA assays in children with IBD.Methods:We studied 32 serum samples from 19 children with IBD treated with infliximab. Serum samples were collected immediately before drug infusion (trough level). Infliximab was measured using 2 POC infliximab assays, Quantum Blue (POC IFX/QB) and Rida Quick (POC IFX/RQ), and 2 ELISA assays: Lisa‐Tracker (used as primary reference), and Promonitor (used as second control). Intraclass correlation coefficient (ICC) was assessed for quantitative comparison. Qualitative analysis was also performed to evaluate whether POC assays would correctly classify infliximab serum according to a target window (between 3 and 7 μg/mL).Results:ICC was 0.82 and 0.87 for POC IFX/QB and POC IFX/RQ with the primary reference ELISA assay, respectively; ICC between the 2 ELISA assays was 0.87. Classification of results according to therapeutic intervals showed good agreement between pairs of assays, with kappa of 0.67 and 0.80 for POC IFX/QB and POC IFX/RQ, respectively, with reference ELISA, and 0.81 between the 2 ELISAs. Accuracy of POC assays was better for drug levels <3 μg/mL.Conclusions:POC infliximab assays showed good agreement with traditional ELISA assays. POC devices may represent a viable option for real‐time therapeutic drug monitoring in children treated with infliximab.
Identifying predictors of HPV-related head and neck squamous cell carcinoma progression and survival through patient-derived models
Authors: Facompre ND , Rajagopalan P , Sahu V , Pearson AT , Montone KT , James CD , Gleber-Netto FO , Weinstein GS , Jalaly J , Lin A , Rustgi AK , Nakagawa H , Califano JA , Pickering CR , White EA , Windle B , Morgan IM , Cohen RB , Gimotty PA , Basu D 
Published: May 2019

AbstractTherapeutic innovation for human papilloma virus-related (HPV+) head and neck squamous cell carcinomas (HNSCCs) is impaired by inadequate biomarkers and preclinical models. This study addressed both limitations using the largest panel of HPV+ HNSCC patient-derived xenografts (PDXs) and organoids described to date. Whole exome profiles of the PDXs were compared to those of HPV+ human tumors and cell lines, and genetic features of the models were analyzed relative to their growth properties and outcomes of their patients of origin. PDX engraftment enriched for negatively prognostic NOTCH1 mutations while preserving multiple features lost in existing cell lines, includingPIK3CAmutations,TRAF3deletion, and absence ofEGFRamplification. Observation of more mutations in faster-growing models facilitated identification of an association between mutational burden and local progression in both HPV+ and HPV-HNSCCs. Reduced E7 and p16INK4Alevels found in a PDX from a lethal case led to detection of a similar profile among recurrent HPV+ HNSCCs in two patient cohorts, where low E2F target gene expression downstream of E7 predicted recurrence and mortality. Our findings bridge a critical gap in preclinical models for HPV+ HNSCCs and simultaneously reveal novel applications for mutational burden and E2F target dysregulation in biomarker development.
Evidence of a Causal Association Between Cancer and Alzheimer’s Disease: a Mendelian Randomization Analysis
Authors: Seddighi Sahba , Houck Alexander L , Rowe James B , Pharoah Paul DP 
Published: May 2019

AbstractObjectivesTo determine whether cancer confers protection against Alzheimer’s disease and to evaluate the relationship in the context of smoking-related cancers versus non-smoking related cancersDesignMendelian randomization analysis using cancer-associated genetic variants as instrumental variablesSettingInternational Genomics of Alzheimer’s ProjectParticipants17,008 Alzheimer’s disease cases and 37,154 controlsMain outcome measuresOdds ratio of Alzheimer’s disease per 1-unit higher log odds of genetically predicted cancerResultsWe found that genetically predicted lung cancer (OR 0.91, 95% CI 0.84-0.99, p=0.019), leukemia (OR 0.98, 95% CI 0.96-0.995, p=0.012), and breast cancer (OR 0.94, 95% CI 0.89-0.99, p=0.028) were associated with 9.0%, 2.4%, and 5.9% lower odds of Alzheimer’s disease, respectively, per 1-unit higher log odds of cancer. When genetic predictors of all cancers were pooled, cancer was associated with 2.5% lower odds of Alzheimer’s disease (OR 0.98, 95% CI 0.96-0.988, p=0.00027) per 1-unit higher log odds of cancer. Finally, genetically predicted smoking-related cancers showed a more robust inverse association with Alzheimer’s disease than non-smoking related cancers (5.2% lower odds, OR 0.95, 95% CI 0.92-0.98, p=0.0026, vs. 1.9% lower odds, OR 0.98, 95% CI 0.97-0.995, p=0.0091).ConclusionsGenetically predicted lung cancer, leukemia, breast cancer, and all cancers in aggregate are associated with lower odds of incident Alzheimer’s disease. Furthermore, the risk of Alzheimer’s disease was lower in smoking-related versus non-smoking related cancers. These results add to the substantial epidemiological evidence of an inverse association between history of cancer and lower odds of Alzheimer’s disease, by suggesting a causal basis for this relationship.