bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacy stakeholder reports on ethical and logistical considerations in anti-opioid vaccine development
Authors: Wartenweiler Vincent , Chung Grace , Stewart Amy , Wenthur Cody 
Published: March 2021

Abstract
Background
As opioid use disorder (OUD) incidence and its associated deaths continue to persist at elevated rates, the development of novel treatment modalities is warranted. Recent strides in this therapeutic area include novel anti-opioid vaccine approaches. This work compares logistical and ethical considerations surrounding currently available interventions for opioid use disorder with an anti-opioid vaccine approach.

Methods
The opinions of student pharmacists and practicing pharmacists assessing knowledge, perceptions, and attitudes toward current and future OUD management strategies were characterized using a staged, multi-modal research approach incorporating a focus group, pilot survey development and refinement, and final survey deployment. Survey responses were assessed using one- and two-way parametric and non-parametric analyses where appropriate, and multi-dimensional matrix profiles were compared using z-tests following an exhaustive combinatorial sum of differences calculation between items within each compared matrix.

Results
Focus group content analysis revealed a high level of agreeableness among participants regarding anti-opioid vaccine technology and a sense of shared ownership regarding solutions to the opioid epidemic at large. Pilot survey results demonstrated subject ability to consider both pragmatic and ethical considerations related to current therapeutics and novel interventions in a single instrument, with high endurance amongst engaged subjects. Access inequality was the most concerning ethical consideration identified for anti-opioid vaccines. Support for anti-opioid vaccine implementation across various clinical scenarios was strongest for voluntary use amongst individuals in recovery, and lowest for mandatory use in at-risk individuals.

Conclusions
Ethical and logistical concerns surrounding anti-opioid vaccines were largely similar to those for current OUD therapeutics overall. Anti-opioid vaccines were endorsed as helpful potential additions to current OUD therapeutic approaches, particularly for voluntary use in the later stages of clinical progression.
Considerations for applying bioethics norms to a biopharmaceutical industry setting
Authors:   The Biopharmaceutical Bioethics Working Group, Van Campen Luann E. , Poplazarova Tatjana , Therasse Donald G. , Turik Michael 
Published: March 2021

AbstractBackgroundThe biopharmaceutical industry operates at the intersection of life sciences, clinical research, clinical care, public health, and business, which presents distinct operational and ethical challenges. This setting merits focused bioethics consideration to complement legal compliance and business ethics efforts. However, bioethics as applied to a biopharmaceutical industry setting often is construed either too broadly or too narrowly with little examination of its proper scope.Main textAny institution with a scientific or healthcare mission should engage bioethics norms to navigate ethical issues that arise from the conduct of biomedical research, delivery of clinical care, or implementation of public health programs. It is reasonable to assume that while bioethics norms must remain constant, their application will vary depending on the characteristics of a given setting. Context “specification” substantively refines ethics norms for a particular discipline or setting and is an expected, needed and progressive ethical activity. In order for this activity to be meaningful, the scope for bioethics application and the relevant contextual factors of the setting need to be delineated and appreciated. This paper defines biopharmaceutical bioethics as:the application of bioethics norms (concepts, principles, and rules) to the research, development, supply, commercialization, and clinical use of biopharmaceutical healthcare products. It provides commentary on this definition, and presents five contextual factors that need to be considered when applying bioethics norms to a biopharmaceutical industry setting: (1) dual missions; (2) timely and pragmatic guidance; (3) resource stewardship; (4) multiple stakeholders; and (5) operational complexity.ConclusionUnderstanding the scope of the biopharmaceutical enterprise and contextual factors of a biopharmaceutical industry setting is foundational for the application of bioethics norms. Establishing a common language and approach for biopharmaceutical bioethics will facilitate breadth and depth of discussion and subsequent implementation to benefit patients, the healthcare system and society.
The impact of the COVID-19 pandemic on child health and the provision of Care in Paediatric Emergency Departments: a qualitative study of frontline emergency care staff
Authors: Conlon Ciara , McDonnell Thérèse , Barrett Michael , Cummins Fergal , Deasy Conor , Hensey Conor , McAuliffe Eilish , Nicholson Emma 
Published: March 2021

Abstract
Background
The COVID-19 pandemic and subsequent public health guidance to reduce the spread of the disease have wide-reaching implications for children’s health and wellbeing. Furthermore, paediatric emergency departments (EDs) have rapidly adapted provision of care in response to the pandemic. This qualitative study utilized insight from multidisciplinary frontline staff to understand 1) the changes in paediatric emergency healthcare utilization during COVID-19 2) the experiences of working within the restructured health system.

Methods
Fifteen semi-structured interviews were conducted with frontline staff working in two paediatric EDs and two mixed adult and children EDs. Participants included emergency medicine clinicians (n = 5), nursing managerial staff (n = 6), social workers (n = 2) and nursing staff (n = 2). Thematic Analysis (TA) was applied to the data to identify key themes.

Results
The pandemic and public health restrictions have had an adverse impact on children’s health and psychosocial wellbeing, compounded by difficulty in accessing primary and community services. The impact may have been more acute for children with disabilities and chronic health conditions and has raised child protection issues for vulnerable children. EDs have shown innovation and agility in the structural and operational changes they have implemented to continue to deliver care to children, however resource limitations and other challenges must be addressed to ensure high quality care delivery and protect the wellbeing of those tasked with delivering this care.

Conclusions
The spread of COVID-19 and subsequent policies to address the pandemic has had wide-reaching implications for children’s health and wellbeing. The interruption to health and social care services is manifesting in myriad ways in the ED, such as a rise in psychosocial presentations. As the pandemic continues to progress, policy makers and service providers must ensure the continued provision of essential health and social services, including targeted responses for those with existing conditions.
Sero-epidemiology and associated risk factors of brucellosis among sheep and goat population in the south western Nepal: a comparative study
Authors: Gompo Tulsi Ram , Shah Rubina , Tiwari Ishwari , Gurung Yam Bahadur 
Published: March 2021

Abstract
Background
Brucellosis is a zoonotic disease caused by Brucella spp. In Nepal, the presence of brucellosis in small ruminants, namely sheep and goats, has impacted farmers’ livelihood and the food safety of consumers. A cross-sectional study was conducted in Rupandehi district of Nepal during January to March 2020 to investigate the seroepidemiology and associated risk factors of brucellosis in the sheep and goat population. Altogether, 19 sheep and 60 goat farms in the district were visited. Owners were interviewed to get information on animals, including their management and movement patterns. Three hundred fifty-seven samples (80 sheep and 277 goat samples) were collected proportionately based on farm sizes. Each serum sample was tested with Rose Bengal Test and ELISA to estimate the seropositivity of brucellosis. Logistic regression was carried out to calculate corresponding odds ratios of each variable associated with detection of brucellosis.

Results
At the farm level, 31.6% (6/19; 95% CI: 12, 54%) of sheep farms and 3.3% (2/60, 95% CI: 0.9, 11.4%) of goat farms were seropositive to brucellosis. Out of 80 sheep serum samples, 12 (15%; 95% CI: 8.79–24.41%) and out of 277 goat serum samples, three (1.1%; 95% CI: 0.37–3.14%) were seropositive to brucellosis. Age greater than 1.5 years (OR = 5.56, 95% CI: 1.39, 29.38; p = 0.02) and herd size of greater than 100 (OR = 4.74, 95% CI: 1.23, 20.32, p = 0.03) were identified as significant risk factors for seropositivity of brucellosis in the sheep population. While in the goat population, none of the variables was identified as a significant risk factor.

Conclusion
The study provides evidence that the older sheep and the sheep from the large herds were at higher risk of brucellosis. A control program should be put in place immediately in the sheep population because they may transmit infections to other livestock as they were regularly moved for grazing and selling purposes. Also, strict biosecurity measures should be implemented among pastoralists to prevent brucellosis transmission in them. We suggest further one health-based study to reveal the transmission dynamics of brucellosis between animals and humans.
Association between cholesterol efflux capacity and peripheral artery disease in coronary heart disease patients with and without type 2 diabetes: from the CORDIOPREV study
Authors: Yubero-Serrano Elena M. , Alcalá-Diaz Juan F. , Gutierrez-Mariscal Francisco M. , Arenas-de Larriva Antonio P. , Peña-Orihuela Patricia J. , Blanco-Rojo Ruth , Martinez-Botas Javier , Torres-Peña Jose D. , Perez-Martinez Pablo , Ordovas Jose M. , Delgado-Lista Javier , Gómez-Coronado Diego , Lopez-Miranda Jose 
Published: March 2021

Abstract
Background
Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association.

Methods
CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma was performed.

Results
The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment.

Conclusions
Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients.
Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT00924937. Unique Identifier: NCT00924937
Impact of type 2 diabetes mellitus on left ventricular diastolic function in patients with essential hypertension: evaluation by volume-time curve of cardiac magnetic resonance
Authors: Yan Wei-feng , Gao Yue , Zhang Yi , Guo Ying-kun , Wang Jin , Jiang Li , Li Yuan , Yang Zhi-gang 
Published: March 2021

Abstract
Background
Essential hypertension and type 2 diabetes mellitus (T2DM) are two common chronic diseases that often coexist, and both of these diseases can cause heart damage. However, the additive effects of essential hypertension complicated with T2DM on left ventricle (LV) diastolic function have not been fully illustrated. This study aims to investigate whether T2DM affects the diastolic function of the LV in patients with essential hypertension using the volume-time curve from cardiac magnetic resonance (CMR).

Methods
A total of 124 essential hypertension patients, including 48 with T2DM [HTN(T2DM +) group] and 76 without T2DM [HTN(T2DM-) group], and 52 normal controls who underwent CMR scans were included in this study. LV volume-time curve parameters, including the peak ejection rate (PER), time to peak ejection rate (PET), peak filling rate (PFR), time to peak filling rate from end-systole (PFT), PER normalized to end-diastolic volume (PER/EDV), and PFR normalized to EDV (PFR/EDV), were measured and compared among the three groups. Multivariate linear regression analyses were performed to determine the effects of T2DM on LV diastolic dysfunction in patients with hypertension. Pearson correlation was used to analyse the correlation between the volume-time curve and myocardial strain parameters.

Results
PFR and PFR/EDV decreased from the control group, through HTN(T2DM −), to HTN(T2DM +) group. PFT in the HTN(T2DM-) group and HTN(T2DM +) group was significantly longer than that in the control group. The LV remodelling index in the HTN(T2DM −) and HTN(T2DM +) groups was higher than that in the normal control group, but there was no significant difference between the HTN(T2DM −) and HTN(T2DM +) groups. Multiple regression analyses controlling for covariates of systolic blood pressure, age, sex, and heart rate demonstrated that T2DM was independently associated with PFR/EDV (β = 0.252, p < 0.05). The volume-time curve method has good repeatability, and there is a significant correlation between volume-time curve parameters (PER/EDV and PFR/EDV) and myocardial peak strain rate, especially circumferential peak strain rate, which exhibited the highest correlation (r = − 0.756 ~ 0.795).

Conclusions
T2DM exacerbates LV diastolic dysfunction in patients with essential hypertension. The LV filling model changes reflected by the CMR volume-time curve could provide more information for early clinical intervention.
Treatment with direct oral anticoagulants or warfarin and the risk for incident diabetes among patients with atrial fibrillation: a population‐based cohort study
Authors: Cheung Ching-Lung , Sing Chor-Wing , Lau Wallis C. Y. , Li Gloria H. Y. , Lip Gregory Y. H. , Tan Kathryn C. B. , Cheung Bernard M. Y. , Chan Esther W. Y. , Wong Ian C. K. 
Published: March 2021

Abstract
Background
Diabetes mellitus is a common comorbidity of atrial fibrillation (AF), which can complicate the management of AF. The pharmacology of oral anticoagulants (OACs) have been implicated in pathogenesis of diabetes, but the relationship between different OACs and risk of diabetes remains unexamined. This study aimed to evaluate the risk of diabetes with use of different OACs in AF patients.

Methods
Population-based retrospective cohort study using an electronic healthcare database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with AF from 2014 through 2018 and prescribed OACs were included and followed till December 31, 2019. Inverse probability of treatment weighting based on the propensity score (PS) is used to address potential bias due to nonrandomized allocation of treatment. The risks ofdiabetes were compared between different new OAC users using propensity score-weighted cumulative incidence differences (CID).

Results
There were 13,688 new users of OACs (warfarin: n = 3454; apixaban: n = 3335; dabigatran: n = 4210; rivaroxaban: n = 2689). The mean age was 75.0 (SD, 11.2), and 6,550 (47.9%) were women. After a median follow-up of 0.93 years (interquartile range, 0.21–1.92 years), 698 incident diabetes cases were observed. In Cox-regression analysis, dabigatran use was significantly associated with reduced risk of diabetes when compared with warfarin use [HR 0.69 (95% CI 0.56–0.86; P < 0.001)], with statistically insignificant associations observed for use of apixaban and rivaroxaban. The corresponding adjusted CIDs at 2 years after treatment with apixaban, dabigatran, and rivaroxaban users when compared with warfarin were − 2.06% (95% CI − 4.08 to 0.16%); − 3.06% (95% CI − 4.79 to − 1.15%); and − 1.8% (− 3.62 to 0.23%). In head-to-head comparisons between women DOAC users, dabigatran was also associated with a lower risk of diabetes when compared with apixaban and rivaroxaban.

Conclusions
Among adults with AF receiving OACs, the use of dabigatran had the lowest risk of diabetes when compared with warfarin use.
Machine learning associated with respiratory oscillometry: a computer-aided diagnosis system for the detection of respiratory abnormalities in systemic sclerosis
Authors: Andrade Domingos S. M. , Ribeiro Luigi Maciel , Lopes Agnaldo J. , Amaral Jorge L. M. , Melo Pedro L. 
Published: March 2021

AbstractIntroductionThe use of machine learning (ML) methods would improve the diagnosis of respiratory changes in systemic sclerosis (SSc). This paper evaluates the performance of several ML algorithms associated with the respiratory oscillometry analysis to aid in the diagnostic of respiratory changes in SSc. We also find out the best configuration for this task.MethodsOscillometric and spirometric exams were performed in 82 individuals, including controls (n = 30) and patients with systemic sclerosis with normal (n = 22) and abnormal (n = 30) spirometry. Multiple instance classifiers and different supervised machine learning techniques were investigated, including k-Nearest Neighbors (KNN), Random Forests (RF), AdaBoost with decision trees (ADAB), and Extreme Gradient Boosting (XGB).Results and discussionThe first experiment of this study showed that the best oscillometric parameter (BOP) was dynamic compliance, which provided moderate accuracy (AUC = 0.77) in the scenario control group versus patients with sclerosis and normal spirometry (CGvsPSNS). In the scenario control group versus patients with sclerosis and altered spirometry (CGvsPSAS), the BOP obtained high accuracy (AUC = 0.94). In the second experiment, the ML techniques were used. In CGvsPSNS, KNN achieved the best result (AUC = 0.90), significantly improving the accuracy in comparison with the BOP (p < 0.01), while in CGvsPSAS, RF obtained the best results (AUC = 0.97), also significantly improving the diagnostic accuracy (p < 0.05). In the third, fourth, fifth, and sixth experiments, different feature selection techniques allowed us to spot the best oscillometric parameters. They resulted in a small increase in diagnostic accuracy in CGvsPSNS (respectively, 0.87, 0.86, 0.82, and 0.84), while in the CGvsPSAS, the best classifier's performance remained the same (AUC = 0.97).ConclusionsOscillometric principles combined with machine learning algorithms provide a new method for diagnosing respiratory changes in patients with systemic sclerosis. The present study's findings provide evidence that this combination may help in the early diagnosis of respiratory changes in these patients.
Decomposition of high-frequency electrical conductivity into extracellular and intracellular compartments based on two-compartment model using low-to-high multi-b diffusion MRI
Authors: Lee Mun Bae , Kim Hyung Joong , Kwon Oh In 
Published: March 2021

Abstract
Background
As an object’s electrical passive property, the electrical conductivity is proportional to the mobility and concentration of charged carriers that reflect the brain micro-structures. The measured multi-b diffusion-weighted imaging (Mb-DWI) data by controlling the degree of applied diffusion weights can quantify the apparent mobility of water molecules within biological tissues. Without any external electrical stimulation, magnetic resonance electrical properties tomography (MREPT) techniques have successfully recovered the conductivity distribution at a Larmor-frequency.

Methods
This work provides a non-invasive method to decompose the high-frequency conductivity into the extracellular medium conductivity based on a two-compartment model using Mb-DWI. To separate the intra- and extracellular micro-structures from the recovered high-frequency conductivity, we include higher b-values DWI and apply the random decision forests to stably determine the micro-structural diffusion parameters.

Results
To demonstrate the proposed method, we conducted phantom and human experiments by comparing the results of reconstructed conductivity of extracellular medium and the conductivity in the intra-neurite and intra-cell body. The phantom and human experiments verify that the proposed method can recover the extracellular electrical properties from the high-frequency conductivity using a routine protocol sequence of MRI scan.

Conclusion
We have proposed a method to decompose the electrical properties in the extracellular, intra-neurite, and soma compartments from the high-frequency conductivity map, reconstructed by solving the electro-magnetic equation with measured B1 phase signals.
The Arab region’s contribution to global COVID-19 research: Bibliometric and visualization analysis
Authors: Zyoud Sa’ed H. 
Published: March 2021

Abstract
Background
At the global level and in the Arab world, particularly in low-income countries, COVID-19 remains a major public health issue. As demonstrated by an incredible number of COVID-19-related publications, the research science community responded rapidly. Therefore, this study was intended to assess the growing contribution of the Arab world to global research on COVID-19.

Methods
For the period between December 2019 and March 2021, the search for publications was conducted via the Scopus database using terms linked to COVID-19. VOSviewer 1.6.16 software was applied to generate a network map to assess hot topics in this area and determine the collaboration patterns between different countries. Furthermore, the research output of Arab countries was adjusted in relation to population size and gross domestic product (GDP).

Results
A total of 143,975 publications reflecting the global overall COVID-19 research output were retrieved. By restricting analysis to the publications published by the Arab countries, the research production was 6131 documents, representing 4.26% of the global research output regarding COVID-19. Of all these publications, 3990 (65.08%) were original journal articles, 980 (15.98%) were review articles, 514 (8.38%) were letters and 647 (10.55%) were others, such as editorials or notes. The highest number of COVID-19 publications was published by Saudi Arabia (n = 2186, 35.65%), followed by Egypt (n = 1281, 20.78%) and the United Arab Emirates (UAE), (n = 719, 11.73%). After standardization by population size and GDP, Saudi Arabia, UAE and Lebanon had the highest publication productivity. The collaborations were mostly with researchers from the United States (n = 968), followed by the United Kingdom (n = 661). The main research lines identified in COVID-19 from the Arab world are related to: public health and epidemiology; immunological and pharmaceutical research; signs, symptoms and clinical diagnosis; and virus detection.

Conclusions
A novel analysis of the latest Arab COVID-19-related studies is discussed in the current study and how these findings are connected to global production. Continuing and improving future collaboration between developing and developed countries will also help to facilitate the sharing of responsibilities for COVID-19 in research results and the implementation of policies for COVID-19.