bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opioid underuse in terminal care of long-term care facility residents with pain and/or dyspnoea: A cross-sectional PACE-survey in six European countries
Authors: Tanghe Marc , Van Den Noortgate Nele , Deliens Luc , Smets Tinne , Onwuteaka-Philipsen Bregje , Szczerbińska Katarzyna , Finne-Soveri Harriet , Payne Sheila , Gambassi Giovanni , Van den Block Lieve , Piers Ruth 
Published: April 2020

Background/objectives: Opioids relieve symptoms in terminal care. We studied opioid underuse in long-term care facilities, defined as residents without opioid prescription despite pain and/or dyspnoea, 3 days prior to death. Design and setting: In a proportionally stratified randomly selected sample of long-term care facilities in six European Union countries, nurses and long-term care facility management completed structured after-death questionnaires within 3 months of residents’ death. Measurements: Nurses assessed pain/dyspnoea with Comfort Assessment in Dying with Dementia scale and checked opioid prescription by chart review. We estimated opioid underuse per country and per symptom and calculated associations of opioid underuse by multilevel, multivariable analysis. Results: Nurses’ response rate was 81.6%, 95.7% for managers. Of 901 deceased residents with pain/dyspnoea reported in the last week, 10.6% had dyspnoea, 34.4% had pain and 55.0% had both symptoms. Opioid underuse per country was 19.2% (95% confidence interval: 12.9–27.2) in the Netherlands, 25.2% (18.3–33.6) in Belgium, 29.3% (16.9–45.8) in England, 33.7% (26.2–42.2) in Finland, 64.6% (52.0–75.4) in Italy and 79.1% (71.2–85.3) in Poland ( p < 0.001). Opioid underuse was 57.2% (33.0–78.4) for dyspnoea, 41.2% (95% confidence interval: 21.9–63.8) for pain and 37.4% (19.4–59.6) for both symptoms ( p = 0.013). Odds of opioid underuse were lower (odds ratio: 0.33; 95% confidence interval: 0.20–0.54) when pain was assessed. Conclusion: Opioid underuse differs between countries. Pain and dyspnoea should be formally assessed at the end-of-life and taken into account in physicians orders.
The association of Helicobacter pylori CagA EPIYA motifs and vacA genotypes with homologous recombination repair markers during the gastric precancerous cascade
Authors: Mi Yang , Dong Haibin , Sun Xiangdong , Ren Feifei , Tang Youcai , Zheng Pengyuan 
Published: April 2020

Background: Helicobacter pylori-induced DNA damage and impaired homologous recombination repair are vital molecular mechanisms for gastric cancer, which mainly count on its virulence factors cytotoxic-associated gene A (CagA) and vacuolating cytotoxin A (VacA). However, the relationship between H. pylori CagA EPIYA motifs and vacA genotypes with DNA damage and homologous recombination repair markers is still not clear. Methods: H. pylori positive and negative gastric biopsies were taken from 165 subjects with different gastric precancerous pathologic stages, and DNA damage marker γH2AX and key homologous recombination repair proteins (CtIP and Rad51) were investigated for their association with H. pylori CagA EPIYA motifs and vacAs-, m-, i-, and d-region genotypes and histology (Sydney classification). Results: Out of 165 patients, 78 were identified as H. pylori-positive. CagA EPIYA motifs were identified as AB, ABC, and ABD in 2 (3.3%), 21 (35%), and 37 (61.7%) patients, respectively, while vacA alleles were identified as: s1, s2, m1, m2, i1, i2, d1, and d2 in 50 (89.3%), 6 (10.7%), 24 (42.9%), 32 (57.1%), 45 (80.4%), 11 (19.6%), 40 (71.4%), and 16 (28.6%) patients, respectively. vacAs1m1i1d1, s1m2i1d1, and s1m2i2d2 were the most prevailing genotypes. γH2AX was highly localized in H. pylori-positive tissues with corresponding CagA EPIYA motifs and vacA genotypes, while Rad51 and CtIP signals were weak. Conclusion: H. pylori were positively correlated with the DNA damage marker in precancerous lesions, but were negatively correlated with the key homologous recombination repair proteins, which may be due to the specific CagA EPIYA motifs and vacA genotypes.
Inhibition of the Wnt/β-catenin pathway enhances antitumor immunity in ovarian cancer
Authors: Doo David W. , Meza-Perez Selene , Londoño Angelina I. , Goldsberry Whitney N. , Katre Ashwini A. , Boone Jonathan D. , Moore Dylana J. , Hudson Cindy T. , Betella Ilaria , McCaw Tyler R. , Gangrade Abhishek , Bao Riyue , Luke Jason J. , Yang Eddy S. , Birrer Michael J. , Starenki Dmytro , Cooper Sara J. , Buchsbaum Donald J. , Norian Lyse A. , Randall Troy D. , Arend Rebecca C. 
Published: April 2020

Background: The Wnt/β-catenin pathway is linked to tumorigenesis in a variety of tumors and promotes T cell exclusion and resistance to checkpoint inhibitors. We sought to determine whether a small molecule inhibitor of this pathway, WNT974, would impair tumor growth, affect gene expression patterns, and improve the immune response in human and murine ovarian cancer models. Methods: Human ovarian cancer cells were treated with WNT974 in vitro. RNAseq libraries were constructed and differences in gene expression patterns between responders and nonresponders were compared to The Cancer Genome Atlas (TCGA). Mice with subcutaneous or intraperitoneal ID8 ovarian cancer tumors were treated with WNT974, paclitaxel, combination, or control. Tumor growth and survival were measured. Flow cytometry and β-TCR repertoire analysis were used to determine the immune response. Results: Gene expression profiling revealed distinct signatures in responders and nonresponders, which strongly correlated with T cell infiltration patterns in the TCGA analysis of ovarian cancer. WNT974 inhibited tumor growth, prevented ascites formation, and prolonged survival in mouse models. WNT974 increased the ratio of CD8+ T cells to T regulatory cells (Tregs) in tumors and enhanced the effector functions of infiltrating CD4+ and CD8+ T cells. Treatment also decreased the expression of inhibitory receptors on CD8+ T cells. Combining WNT974 with paclitaxel further reduced tumor growth, prolonged survival, and expanded the T cell repertoire. Conclusions: These findings suggest that inhibiting the Wnt/β-catenin pathway may have a potent immunomodulatory effect in the treatment of ovarian cancer, particularly when combined with paclitaxel.
DOACs vs LMWHs in hospitalized medical patients: a systematic review and meta-analysis that informed 2018 ASH guidelines
Authors: Neumann Ignacio , Izcovich Ariel , Zhang Yuqing , Rada Gabriel , Kahn Susan R. , Spencer Frederick , Rezende Suely , Dentali Franchesco , Bauer Kenneth , Morgano Gian Paolo , Yepes-Nuñez Juan J. , Nieuwlaat Robby , Wiercioch Wojtek , Lu Liming , Wu Jiaming , Cushman Mary , Schunemann Holger 
Published: April 2020

Abstract
Venous thromboembolism (VTE) is a relatively frequent complication in hospitalized patients, especially in those with risk factors. The benefit of using direct oral anticoagulants (DOACs) for prevention is controversial. This systematic review was performed as part of the American Society of Hematology (ASH) guidelines on VTE, developed in partnership with McMaster University. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Epistemonikos were used as data sources from date of inception to November 2019. We included randomized trials in patients hospitalized for an acute medical disease, evaluating any DOACs vs other pharmacological prophylaxis, and included 3 trials with low risk of bias. We analyzed the effects of DOACs vs low-molecular-weight heparins (LMWHs) at 2 different time points: at the end of the short-term treatment phase (both drugs given for the same period of time) and at the end of the extended prophylaxis period (extended DOACs vs a shorter course of LMWHs). We observed that the use of DOACs did not reduce the risk of pulmonary embolism or symptomatic deep venous thrombosis (DVT) in comparison with LMWHs. However, the risk of major bleeding was slightly increased. Additionally, we observed that the benefit of DOACs previously reported was largely based on the reduction of asymptomatic DVT and was not apparent when only symptomatic events were considered. The use of DOACs in hospitalized medical patients slightly increases the risk of major bleeding with no appreciable benefit over LMWHs.
Thrombolytics for venous thromboembolic events: a systematic review with meta-analysis
Authors: Izcovich Ariel , Criniti Juan M. , Popoff Federico , Lu Liming , Wu Jiaming , Ageno Walter , Witt Daniel M. , Jaff Michael R. , Schulman Sam , Manja Veena , Verhamme Peter , Rada Gabriel , Zhang Yuqing , Nieuwlaat Robby , Wiercioch Wojtek , Schünemann Holger J. , Neumann Ignacio 
Published: April 2020

AbstractThrombolytic therapy might reduce venous thromboembolism–related mortality and morbidity, but it could also increase the risk of major bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of thrombolytics in patients with pulmonary embolism (PE) and/or deep venous thrombosis (DVT). We searched Medline, Embase, and Cochrane databases for relevant randomized controlled trials up to February 2019. Multiple investigators independently screened and collected data. We included 45 studies (4740 participants). Pooled estimates of PE studies indicate probable reduction in mortality with thrombolysis (risk ratio [RR], 0.61; 95% confidence interval [CI], 0.40-0.94) (moderate certainty) and possible reduction in nonfatal PE recurrence (RR, 0.56; 95% CI, 0.35-0.89) (low certainty). Pooled estimates of DVT studies indicate the possible absence of effects on mortality (RR, 0.77; 95% CI, 0.26-2.28) (low certainty) and recurrent DVT (RR, 0.99; 95% CI, 0.56-1.76) (low certainty), but possible reduction in postthrombotic syndrome (PTS) with thrombolytics (RR, 0.70; 95% CI, 0.59-0.83) (low certainty). Pooled estimates of the complete body of evidence indicate increases in major bleeding (RR, 1.89; 95% CI, 1.46-2.46) (high certainty) and a probable increase in intracranial bleeding (RR, 3.17; 95% CI 1.19-8.41) (moderate certainty) with thrombolytics. Our findings indicate that thrombolytics probably reduce mortality in patients with submassive- or intermediate-risk PE and may reduce PTS in patients with proximal DVT at the expense of a significant increase in major bleeding. Because the balance between benefits and harms is profoundly influenced by the baseline risks of critical outcomes, stakeholders involved in decision making would need to weigh these effects to define which clinical scenarios merit the use of thrombolytics.
Longer shared parental leave is associated with longer duration of breastfeeding: a cross-sectional study among Swedish mothers and their partners
Authors: Grandahl Maria , Stern Jenny , Funkquist Eva-Lotta 
Published: April 2020

Abstract
Background
Breastfeeding is associated with health benefits for both the mother and infant and is therefore important to support; moreover, parental leave is a beneficial factor for breastfeeding. The Swedish parental leave is generous, allowing each parent to take 90 days; additionally, a further 300 days can be taken by either parent. Generally, mothers take 70% of the parental leave days, mainly during the first year. However, breastfeeding duration has declined in the last decade, and it is not known how shared parental leave is associated with the duration of breastfeeding.

Aim
To investigate how parental leave is associated with the duration of exclusive and partial breastfeeding of the infant during the first 12 months after birth. An additional aim was to describe infants’ and parents’ characteristics and mode of birth in association with the duration of exclusive and partial breastfeeding.

Methods
This cross-sectional study was part of the Swedish Pregnancy Planning Study, conducted in Sweden in 2012–2015. The parents were recruited at 153 antenatal clinics in nine counties. In total, 813 couples completed a follow-up questionnaire 1 year after birth. Linear regression models were used to analyse the association between parental leave and the duration of breastfeeding.

Results
Infants were exclusively breastfed for, on average, 2.5 months (range 0–12 months) and partially breastfed, on average, 7 months (range 0–12 months). Most of the parental leave was taken by the mother (mean = 10.9 months) during the infant’s first 12 months, while the partner took 3 months, on average. The parental leave (used and planned) during the infant’s first 24 months were, on average, 21 months. In the multivariate linear regression analysis, mothers’ and partners’ high level of education (p < 0.001, p = 0.044, respectively), mothers’ higher age (p = 0.049), non-instrumental vaginal birth (p = 0.004) and longer parental leave for the first 24 months (p < 0.001) were associated with longer duration of partial breastfeeding.

Conclusion
The duration of partial breastfeeding was associated with higher parental educational level, higher age, non-instrumental vaginal birth and longer parental leave.
“From good hearted community members we get volunteers” – an exploratory study of palliative care volunteers across Africa
Authors: Loth Carolin Clara , Namisango Eve , Powell Richard Antony , Pabst Katharina Henny , Leng Mhoira , Hamada Mohamed , Radbruch Lukas 
Published: April 2020

Abstract
Background
Volunteers play a significant role in supporting hospice and palliative care in Africa, but little is known about the types of volunteers, their motivations and roles in service delivery.

Methods
Palliative care experts from 30 African countries were invited to participate in an online survey, conducted in English and French, that consisted of 58 questions on: socio-demographics, the activities, motivation and coordination of volunteers, and an appraisal of recent developments in volunteering. The questionnaire was pre-tested in Uganda. Quantitative data was analysed descriptively with SPSS v22; answers on open-ended questions were analysed using content analysis.

Results
Twenty-five respondents from 21 countries replied to the questionnaire. The typical volunteer was reported to be a female aged between 30 and 50 years. Volunteer roles included, among others: direct patient assistance, providing psychosocial / spiritual support, and assisting patients’ families. Respondents considered altruism, civic engagement and personal gain (for a professional career) as volunteers’ most significant motivational drivers. One in two respondents noted that recruiting volunteers is easy, and cooperation with the communities was often mentioned as helpful. Trainings mostly occurred before the first assignment, with topics covering the palliative care concept, care, psychosocial support and team work. Half of respondents described recent overall volunteering developments as positive, while the other half described problems primarily with financing and motivation. Most volunteers received transportation allowances or bicycles; some received monetary compensation.

Conclusions
The findings show a wide range of volunteering in palliative care. We identified volunteers as typically 30–50 years old, non-professional females, motivated by altruism, a sense of civic engagement and personal gain. Palliative care services benefit from volunteers who take on high workloads and are close to the patients. The main challenges for volunteer programmes are funding and the long-term motivation of volunteers.
Association between organizational citizenship behavior and patient safety culture from nurses’ perspectives: a descriptive correlational study
Authors: Jafarpanah Marzyeh , Rezaei Behrooz 
Published: April 2020

Abstract
Background
Nurses play a key role in providing patient safety. It is known that patient safety requires the improvement of patient safety culture, which can be a difficult process. One of the current challenges of hospitals is to explore the ways to improve patient safety culture. Organizational citizenship behaviors are one of the factors, which can develop organizational culture including safety culture; however, its role is not well established.

Methods
In this cross-sectional study, a stratified random sample of 214 nurses was selected from a largest teaching hospital in west of Iran. The institutional research board approved the study protocol. Data were collected using three self-report questionnaires: demographic information; hospital survey on patient safety culture (HSPSC); and organizational citizenship behaviors questionnaire. Data were analyzed using Spearman’s correlation coefficient test in SPSS (α < 0.05).

Results
Organizational citizenship behaviors were found to be at an intermediate level (56.84 ± 16.22). However, some of its dimensions, including sportsmanship, civic virtue, and courtesy, were at weak levels (< 50%). The mean percentage of positive responses to the patient safety culture was 49.00 ± 14.01. The patient safety culture had significant positive correlations with organizational citizenship behaviors (r = 0.349, P = 0.001) and dimensions of altruism (r = 0.255, P = 0.001), civic virtue (r = 0.434, P = 0.001), and courtesy (r = 0.214, P = 0.001).

Conclusion
Our findings proposed the hypothesis that OCB has a statistical significant impact on PSC. Low levels of civic virtue, sportsmanship and courtesy behaviors may be indicative low nurses’ interest in participating in organizational affairs and nurses’ low attention to measures that prevent harm to their organization. It is recommended that nursing managers focus more on these dimensions, identifying influintioal factors and taking appropriate management measures to promote these behaviors. If our findings are confirmed in future studies, nursing managers can consider the development of organizational citizenship behaviors as one of the managerial approaches for promoting a patient safety culture.
An agent-based model to investigate microbial initiation of Alzheimer’s via the olfactory system
Authors: Sundar Shalini , Battistoni Carly , McNulty Ryan , Morales Fernando , Gorky Jonathan , Foley Henry , Dhurjati Prasad 
Published: April 2020

Abstract
Background
Alzheimer’s disease (AD) is a degenerative brain disease. A novel agent-based modelling framework was developed in NetLogo 3D to provide fundamental insights into the potential mechanisms by which a microbe (eg. Chlamydia pneumoniae) may play a role in late-onset AD. The objective of our initial model is to simulate one possible spatial and temporal pathway of bacterial propagation via the olfactory system, which may then lead to AD symptoms. The model maps the bacteria infecting cells from the nasal cavity and the olfactory epithelium, through the olfactory bulb and into the olfactory cortex and hippocampus regions of the brain.

Results
Based on the set of biological rules, simulated randomized infection by the microbe led to the formation of beta-amyloid (Aβ) plaque and neurofibrillary (NF) tangles as well as caused immune responses. Our initial simulations demonstrated that breathing in C. pneumoniae can result in infection propagation and significant buildup of Aβ plaque and NF tangles in the olfactory cortex and hippocampus. Our model also indicated how mucosal and neural immunity can play a significant role in the pathway considered. Lower immunities, correlated with elderly individuals, had quicker and more Aβ plaque and NF tangle formation counts. In contrast, higher immunities, correlated with younger individuals, demonstrated little to no such formation.

Conclusion
The modelling framework provides an organized visual representation of how AD progression may occur via the olfactory system to better understand disease pathogenesis. The model confirms current conclusions in available research but can be easily adjusted to match future evidence and be used by researchers for their own individual purposes. The goal of our initial model is to ultimately guide further hypothesis refinement and experimental testing to better understand the dynamic system interactions present in the etiology and pathogenesis of AD.
Inference of single-cell phylogenies from lineage tracing data using Cassiopeia
Authors: Jones Matthew G , Khodaverdian Alex , Quinn Jeffrey J , Chan Michelle M , Hussmann Jeffrey A , Wang Robert , Xu Chenling , Weissman Jonathan S , Yosef Nir 
Published: April 2020

AbstractThe pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia—a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Together, these should broadly enable large-scale mammalian lineage tracing efforts. Cassiopeia and its benchmarking resources are publicly available at www.github.com/YosefLab/Cassiopeia.
Toward risk adjustment in mental health in Israel: calculation of risk adjustment rates from large outpatient and inpatient databases
Authors: Kohn Yoav , Shmueli Amir 
Published: April 2020

Abstract
Background
In 2015, mental health services were added to the Israeli National Health Insurance package of services. As such, these services are financed by the budget which is allocated to the Health Plans according to a risk adjustment scheme. An inter-ministerial team suggested a formula by which the mental health budget should be allocated among the Health Plans. Our objective in this study was to develop alternative rates based on individual data, and to evaluate the ones suggested.

Methods
The derivation of the new formula is based on our previous study of all psychiatric inpatients in Israel in the years 2012–2013 (n = 27,446), as well as outpatients in one psychiatric clinic in the same period (n = 6115). Based on Ministry of Health and clinic data we identified predictors of mental health services consumption. Age, gender, marital status and diagnosis were used as risk adjusters to calculate the capitation rates for outpatient care and inpatient care, respectively. All prices of services were obtained from the Ministry of Health tariffs. These rates were modified to include non-users using restricted models.

Results
The mental health capitation scales are typically “humped” with regard to age. The rates for ambulatory care varied from a minimum 0.19 of the average consumption for males above the age of 85 to a maximum of 1.93 times the average for females between the ages of 45–54. For inpatient services the highest rate was 409.25 times the average for single, male patients with schizophrenia spectrum diagnoses, aged 45–54. The overall mental health scale ranges from 2.347 times the average for men aged 45–54, to 0.191 for women aged 85+. The modified scale for the entire post-reform package of benefits (including both mental health care and physical health care) is increasing with age to 4.094 times the average in men aged over 85. The scale is flatter than the pre-reform scale.

Conclusions
The risk adjustment rates calculated for outpatient care are substantially different from the ones suggested by the inter-ministerial team. The inpatient rates are new, and indicate that for patients with schizophrenia, a separate risk-sharing arrangement might be desirable. Adopting the rates developed in this analysis would decrease the budget shares of Clalit and Leumit with their relatively older populations, and increase Maccabi and Meuhedet’s shares. Future research should develop a risk-adjustment scheme which covers directly both mental and physical care provided by the Israeli Health Plans, using their data.