bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience obtaining legal abortion in Uruguay: knowledge, attitudes, and stigma among abortion clients
Authors: Makleff Shelly , Labandera Ana , Chiribao Fernanda , Friedman Jennifer , Cardenas Roosbelinda , Sa Eleuthera , Baum Sarah E. 
Published: December 2019

Abstract
Background
The abortion law in Uruguay changed in 2012 to allow first trimester abortion on request. Implementation of the law in Uruguay has been lauded, but barriers to care, including abortion stigma, remain. This study aimed to assess women’s experiences seeking abortion services and related attitudes and knowledge following implementation of the law in Uruguay.

Methods
We interviewed 207 eligible women seeking abortion services at a high-volume public hospital in Montevideo in 2014. We generated univariate frequencies to describe women’s experiences in care. We conducted regression analysis to examine variations in experiences of stigma by women’s age and number of abortions.

Results
Most of the women felt that abortion was a right, were satisfied with the services they received, and agreed with the abortion law. However, 70% found the five-day waiting period unnecessary. Women experienced greater self-judgement than worries about being judged by others. Younger women in the sample (ages 18–21) reported being more worried about judgment than women 22 years or older (1.02 vs. 0.71 on the ILAS sub-scale). One quarter of participants reported feeling judged while obtaining services. Women with more than one abortion had nearly three times the odds of reporting feeling judged.

Conclusions
These findings highlight the need to address abortion stigma even after the law is changed. Some considerations from Uruguay that may be relevant to other jurisdictions reforming abortion laws include: the need for strategies to reduce judgmental behavior from staff and clinicians towards women seeking abortions, including training in counseling skills and empathic communication; addressing stigmatizing attitudes about abortion through community outreach or communications campaigns; mitigating the potential stigma that may be perpetuated through policies to prevent “repeat” abortions; ensuring that younger women and those with more than one abortion feel welcome and are not mistreated during care; and assessing the necessity of a waiting period. The rapid implementation of legal, voluntary abortion services in Uruguay can serve in many ways as an exemplar, and these findings may inform the process of abortion law reform in other countries.
Opportunities and challenges of integrating genetics education about human diversity into public health nurses’ responsibilities in Japan
Authors: Goda Hiromi , Kawasaki Hiromi , Masuoka Yuko , Kohama Natsu , Rahman Md Moshiur 
Published: December 2019

Abstract
Background
Many genetic tests are now available due to evolution by the Human Genome Project. However, the growing use of genetic testing and screening may not only lead to improvements in public health and health promotion, but also trigger grave ethical, legal, and societal concerns. The involvement of community healthcare providers is expected in the future because they have direct contact with the residents through their health programs. The aims of the current study were to clarify how public health nurses perceive the relationship between genetics and professional duties and to identify opportunities and challenges of integrating genetics education into their professional duties.

Methods
In 2017, data were collected through a focus group interview. Content related to the ‘presence or absence of health consultation related to genetic issues as part of actual job duties’ and ‘training for handling genetic-related health consultations’ was extracted. Entire sentences were coded and categorized based on similar semantic content.

Results
Public health nurses had difficulties in recognizing genetic issues in public health activities. In some cases, genetic contents were included in conversation and consultation with the general public. Through the professional education and experiences, public health nurses needed specialized education, post-graduation studies and mentoring about genetics.

Conclusions
Public health nurses whose professional duties do not directly relate to genetics were exposed to genetics-related episodes on a regular basis without their awareness. The provision of accurate information and knowledge related to genetics by public health nurses would also provide an opportunity for clients to be informed about their latent genetic risks. Hence, there is a need for practical resources, the establishment of collaboration networks, and the development of professional organizations for public health nurses.
Transforming community nursing services in the UK; lessons from a participatory evaluation of the implementation of a new community nursing model in East London based on the principles of the Dutch Buurtzorg model
Authors: Lalani Mirza , Fernandes Jane , Fradgley Richard , Ogunsola Caroline , Marshall Martin 
Published: December 2019

Abstract
Background
Buurtzorg, a model of community nursing conceived in the Netherlands, is widely cited as a promising and evidence-based approach to improving the delivery of integrated nursing and social care in community settings. The model is characterised by high levels of patient and staff satisfaction, professional autonomy exercised through self-managing nursing teams, client empowerment and holistic, patient centred care. This study aimed to examine the extent to which some of the principles of the Buurtzorg model could be adapted for community nursing in the United Kingdom.

Methods
A community nursing model based on the Buurtzorg approach was piloted from June 2017–August 2018 with a team of nurses co-located in a single general practice in the Borough of Tower Hamlets, East London, UK. The initiative was evaluated using a participatory methodology known as the Researcher-in-Residence model. Qualitative data were collected using participant observation of meetings and semi-structured interviews with nurse team members, senior managers, patients/carers and other local stakeholders such as General Practitioners (GP) and social workers. A thematic framework analysis of the data was carried out.

Results
Implementation of a community nursing model based on the Buurtzorg approach in East London had mixed success when assessed against its key principles. Patient experience of the service was positive because of the better access, improved continuity of care and longer appointment times in comparison with traditional community nursing provision. The model also provided important learning for developing service integration in community care, in particular, how to form effective collaborations across the care system with other health and social care professionals. However, some of the core features of the Buurtzorg model were difficult to put into practice in the National Health Service (NHS) because of significant cultural and regulatory differences between The Netherlands and the UK, especially the nurses’ ability to exercise professional autonomy.

Conclusions
Whilst many of the principles of the Buurtzorg model are applicable and transferable to the UK, in particular promoting independence among patients, improving patient experience and empowering frontline staff, the successful embedding of these aims as normalised ways of working will require a significant cultural shift at all levels of the NHS.
Differential impact of malaria control interventions on P. falciparum and P. vivax infections in young Papua New Guinean children
Authors: Ome-Kaius Maria , Kattenberg Johanna Helena , Zaloumis Sophie , Siba Matthew , Kiniboro Benson , Jally Shadrach , Razook Zahra , Mantila Daisy , Sui Desmond , Ginny Jason , Rosanas-Urgell Anna , Karl Stephan , Obadia Thomas , Barry Alyssa , Rogerson Stephen J. , Laman Moses , Tisch Daniel , Felger Ingrid , Kazura James W. , Mueller Ivo , Robinson Leanne J. 
Published: December 2019

Abstract
Introduction
As malaria transmission declines, understanding the differential impact of intensified control on Plasmodium falciparum relative to Plasmodium vivax and identifying key drivers of ongoing transmission is essential to guide future interventions.

Methods
Three longitudinal child cohorts were conducted in Papua New Guinea before (2006/2007), during (2008) and after scale-up of control interventions (2013). In each cohort, children aged 1–5 years were actively monitored for infection and illness. Incidence of malaria episodes, molecular force of blood-stage infections (molFOB) and population-averaged prevalence of infections were compared across the cohorts to investigate the impact of intensified control in young children and the key risk factors for malaria infection and illness in 2013.

Results
Between 2006 and 2008, P. falciparum infection prevalence, molFOB, and clinical malaria episodes reduced by 47%, 59% and 69%, respectively, and a further 49%, 29% and 75% from 2008 to 2013 (prevalence 41.6% to 22.1% to 11.2%; molFOB: 3.4 to 1.4 to 1.0 clones/child/year; clinical episodes incidence rate (IR) 2.6 to 0.8 to IR 0.2 episodes/child/year). P. vivax clinical episodes declined at rates comparable to P. falciparum between 2006, 2008 and 2013 (IR 2.5 to 1.1 to 0.2), while P. vivaxmolFOB (2006, 9.8; 2008, 12.1) and prevalence (2006, 59.6%; 2008, 65.0%) remained high in 2008. However, in 2013, P. vivaxmolFOB (1.2) and prevalence (19.7%) had also substantially declined. In 2013, 89% of P. falciparum and 93% of P. vivax infections were asymptomatic, 62% and 47%, respectively, were sub-microscopic. Area of residence was the major determinant of malaria infection and illness.

Conclusion
Intensified vector control and routine case management had a differential impact on rates of P. falciparum and P. vivax infections but not clinical malaria episodes in young children. This suggests comparable reductions in new mosquito-derived infections but a delayed impact on P. vivax relapsing infections due to a previously acquired reservoir of hypnozoites. This demonstrates the need to strengthen implementation of P. vivax radical cure to maximise impact of control in co-endemic areas. The high heterogeneity of malaria in 2013 highlights the importance of surveillance and targeted interventions to accelerate towards elimination.
Metformin use and cardiovascular outcomes after acute myocardial infarction in patients with type 2 diabetes: a cohort study
Authors: Bromage Daniel I. , Godec Tom R. , Pujades-Rodriguez Mar , Gonzalez-Izquierdo Arturo , Denaxas S. , Hemingway Harry , Yellon Derek M. 
Published: December 2019

Abstract
Background
The use of metformin after acute myocardial infarction (AMI) has been associated with reduced mortality in people with type 2 diabetes mellitus (T2DM). However, it is not known if it is acutely cardioprotective in patients taking metformin at the time of AMI. We compared patient outcomes according to metformin status at the time of admission for fatal and non-fatal AMI in a large cohort of patients in England.

Methods
This study used linked data from primary care, hospital admissions and death registry from 4.7 million inhabitants in England, as part of the CALIBER resource. The primary endpoint was a composite of acute myocardial infarction requiring hospitalisation, stroke and cardiovascular death. The secondary endpoints were heart failure (HF) hospitalisation and all-cause mortality.

Results
4,030 patients with T2DM and incident AMI recorded between January 1998 and October 2010 were included. At AMI admission, 63.9% of patients were receiving metformin and 36.1% another oral hypoglycaemic drug. Median follow-up was 343 (IQR: 1–1436) days. Adjusted analyses showed an increased hazard of the composite endpoint in metformin users compared to non-users (HR 1.09 [1.01–1.19]), but not of the secondary endpoints. The higher risk of the composite endpoint in metformin users was only observed in people taking metformin at AMI admission, whereas metformin use post-AMI was associated with a reduction in risk of all-cause mortality (0.76 [0.62–0.93], P = 0.009).

Conclusions
Our study suggests that metformin use at the time of first AMI is associated with increased risk of cardiovascular disease and death in patients with T2DM, while its use post-AMI might be beneficial. Further investigation in well-designed randomised controlled trials is indicated, especially in view of emerging evidence of cardioprotection from sodium-glucose co-transporter-2 (SGLT2) inhibitors.
Molecular networks of FOXP family: dual biologic functions, interplay with other molecules and clinical implications in cancer progression
Authors: Kim Ju-Ha , Hwang Jisung , Jung Ji Hoon , Lee Hyo-Jung , Lee Dae Young , Kim Sung-Hoon 
Published: December 2019

AbstractThough Forkhead box P (FOXP) transcription factors comprising of FOXP1, FOXP2, FOXP3 and FOXP4 are involved in the embryonic development, immune disorders and cancer progression, the underlying function of FOXP3 targeting CD4 + CD25+ regulatory T (Treg) cells and the dual roles of FOXP proteins as an oncogene or a tumor suppressor are unclear and controversial in cancers to date. Thus, the present review highlighted research history, dual roles of FOXP proteins as a tumor suppressor or an oncogene, their molecular networks with other proteins and noncoding RNAs, cellular immunotherapy targeting FOXP3, and clinical implications in cancer progression.
Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy
Authors: Lim Zuan-Fu , Ma Patrick C. 
Published: December 2019

AbstractThe biggest hurdle to targeted cancer therapy is the inevitable emergence of drug resistance. Tumor cells employ different mechanisms to resist the targeting agent. Most commonly inEGFR-mutant non-small cell lung cancer, secondary resistance mutations on the target kinase domain emerge to diminish the binding affinity of first- and second-generation inhibitors. Other alternative resistance mechanisms include activating complementary bypass pathways and phenotypic transformation. Sequential monotherapies promise to temporarily address the problem of acquired drug resistance, but evidently are limited by the tumor cells’ ability to adapt and evolve new resistance mechanisms to persist in the drug environment. Recent studies have nominated a model of drug resistance and tumor progression under targeted therapy as a result of a small subpopulation of cells being able to endure the drug (minimal residual disease cells) and eventually develop further mutations that allow them to regrow and become the dominant population in the therapy-resistant tumor. This subpopulation of cells appears to have developed through a subclonal event, resulting in driver mutations different from the driver mutation that is tumor-initiating in the most common ancestor. As such, an understanding of intratumoral heterogeneity—the driving force behind minimal residual disease—is vital for the identification of resistance drivers that results from branching evolution. Currently available methods allow for a more comprehensive and holistic analysis of tumor heterogeneity in that issues associated with spatial and temporal heterogeneity can now be properly addressed. This review provides some background regarding intratumoral heterogeneity and how it leads to incomplete molecular response to targeted therapies, and proposes the use of single-cell methods, sequential liquid biopsy, and multiregion sequencing to discover the link between intratumoral heterogeneity and early adaptive drug resistance. In summary, minimal residual disease as a result of intratumoral heterogeneity is the earliest form of acquired drug resistance. Emerging technologies such as liquid biopsy and single-cell methods allow for studying targetable drivers of minimal residual disease and contribute to preemptive combinatorial targeting of both drivers of the tumor and its minimal residual disease cells.
Initial therapy affects duration of diarrhoea in critically ill patients with Clostridioides difficile infection (CDI)
Authors: Manthey Carolin F. , Dranova Darja , Christner Martin , Drolz Andreas , Kluge Stefan , Lohse Ansgar W. , Fuhrmann Valentin 
Published: December 2019

Abstract
Background
Critically ill patients in the intensive care unit (ICU) are at high risk for developing Clostridioides difficile infections (CDI). Risk factors predicting their mortality or standardized treatment recommendations have not been defined for this cohort. Our goal is to determine outcome and mortality associated risk factors for patients at the ICU with CDI by evaluating clinical characteristics and therapy regimens.

Methods
A retrospective single-centre cohort study. One hundred forty-four patients (0.4%) with CDI-associated diarrhoea were included (total 36.477 patients admitted to 12 ICUs from January 2010 to September 2015). Eight patients without specific antibiotic therapy were excluded, so 132 patients were analysed regarding mortality, associated risk factors and therapy regimens using univariate and multivariate regression.

Results
Twenty-eight-day mortality was high in patients diagnosed with CDI (27.3%) compared to non-infected ICU patients (9%). Patients with non CDI-related sepsis (n = 40/132; 30.3%) showed further increase in 28-day mortality (45%; p = 0.003). Initially, most patients were treated with a single CDI-specific agent (n = 120/132; 90.9%), either metronidazole (orally, 35.6%; or IV, 37.1%) or vancomycin (18.2%), or with a combination of antibiotics (n = 12/132; 9.1%). Patients treated with metronidazole IV showed significantly longer duration of diarrhoea > 5 days (p = 0.006). In a multivariate regression model, metronidazole IV as initial therapy was an independent risk factor for delayed clinical cure. Immunosuppressants (p = 0.007) during ICU stay lead to increased 28-day mortality.

Conclusion
Treatment of CDI with solely metronidazole IV leads to a prolonged disease course in critically ill patients.
An adaptive two-arm clinical trial using early endpoints to inform decision making: design for a study of sub-acromial spacers for repair of rotator cuff tendon tears
Authors: Parsons Nick , Stallard Nigel , Parsons Helen , Wells Philip , Underwood Martin , Mason James , Metcalfe Andrew 
Published: December 2019

AbstractBackgroundThere is widespread concern across the clinical and research communities that clinical trials, powered for patient-reported outcomes, testing new surgical procedures are often expensive and time-consuming, particularly when the new intervention is shown to be no better than the standard. Conventional (non-adaptive) randomised controlled trials (RCTs) are perceived as being particularly inefficient in this setting. Therefore, we have developed an adaptive group sequential design that allows early endpoints to inform decision making and show, through simulations and a worked example, that these designs are feasible and often preferable to conventional non-adaptive designs. The methodology is motivated by an ongoing clinical trial investigating a saline-filled balloon, inserted above the main joint of the shoulder at the end of arthroscopic debridement, for treatment of tears of rotor cuff tendons. This research question and setting is typical of many studies undertaken to assess new surgical procedures.MethodsTest statistics are presented based on the setting of two early outcomes, and methods for estimation of sequential stopping boundaries are described. A framework for the implementation of simulations to evaluate design characteristics is also described.ResultsSimulations show that designs with one, two and three early looks are feasible and, with appropriately chosen futility stopping boundaries, have appealing design characteristics. A number of possible design options are described that have good power and a high probability of stopping for futility if there is no evidence of a treatment effect at early looks. A worked example, with code in R, provides a practical demonstration of how the design might work in a real study.ConclusionsIn summary, we show that adaptive designs are feasible and could work in practice. We describe the operating characteristics of the designs and provide guidelines for appropriate values for the stopping boundaries for the START:REACTS (Sub-acromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery) study.Trial registrationISRCTN Registry, ISRCTN17825590. Registered on 5 March 2018.
Distinct patterns of complex rearrangements and a mutational signature of microhomeology are frequently observed in PLP1 copy number gain structural variants
Authors: Bahrambeigi Vahid , Song Xiaofei , Sperle Karen , Beck Christine R. , Hijazi Hadia , Grochowski Christopher M. , Gu Shen , Seeman Pavel , Woodward Karen J. , Carvalho Claudia M. B. , Hobson Grace M. , Lupski James R. 
Published: December 2019

Abstract
Background
We investigated the features of the genomic rearrangements in a cohort of 50 male individuals with proteolipid protein 1 (PLP1) copy number gain events who were ascertained with Pelizaeus-Merzbacher disease (PMD; MIM: 312080). We then compared our new data to previous structural variant mutagenesis studies involving the Xq22 region of the human genome. The aggregate data from 159 sequenced join-points (discontinuous sequences in the reference genome that are joined during the rearrangement process) were studied. Analysis of these data from 150 individuals enabled the spectrum and relative distribution of the underlying genomic mutational signatures to be delineated.

Methods
Genomic rearrangements in PMD individuals with PLP1 copy number gain events were investigated by high-density customized array or clinical chromosomal microarray analysis and breakpoint junction sequence analysis.

Results
High-density customized array showed that the majority of cases (33/50; ~ 66%) present with single duplications, although complex genomic rearrangements (CGRs) are also frequent (17/50; ~ 34%). Breakpoint mapping to nucleotide resolution revealed further previously unknown structural and sequence complexities, even in single duplications. Meta-analysis of all studied rearrangements that occur at the PLP1 locus showed that single duplications were found in ~ 54% of individuals and that, among all CGR cases, triplication flanked by duplications is the most frequent CGR array CGH pattern observed. Importantly, in ~ 32% of join-points, there is evidence for a mutational signature of microhomeology (highly similar yet imperfect sequence matches).

Conclusions
These data reveal a high frequency of CGRs at the PLP1 locus and support the assertion that replication-based mechanisms are prominent contributors to the formation of CGRs at Xq22. We propose that microhomeology can facilitate template switching, by stabilizing strand annealing of the primer using W-C base complementarity, and is a mutational signature for replicative repair.