bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating implementation outcomes (acceptability, adoption, and feasibility) of two initiatives to improve the medication prior authorization process
Authors: Jones Laney K. , Ladd Ilene G. , Gregor Christina , Evans Michael A. , Graham Jove , Gionfriddo Michael R. 
Published: November 2021

Abstract
Background
Processes such as prior authorization (PA) for medications, implemented by health insurance companies to ensure that safe, appropriate, cost-effective, and evidence-based care is provided to all members, have created inefficiencies within healthcare systems. Thus, healthcare systems have implemented supplemental processes to reduce burden and ensure efficiency, timeliness, and appropriate care.

Objective
Evaluate implementation outcomes of two initiatives related to PA for medications: a common record that records all PA-related information that was integrated into the health record and an auto-routing of specialty prescriptions to a hospital-owned specialty pharmacy.

Methods
We conducted semi-structured interviews with medical staff to understand their experience, acceptability, adoption, and feasibility of these initiatives guided by Proctor’s Framework for Implementation Outcomes. Transcripts were analyzed using consensus coding.

Results
Eleven medical staff participated in semi-structured interviews. The two initiatives were analyzed together because the findings were similar across both for our outcomes of acceptability, adoption, and feasibility. Participants found the implemented initiatives to be acceptable and beneficial but felt there were still challenges with the new workflow. The initiatives were fully adopted by only one clinic site within the healthcare system, but limitations arose when adopting to another site. Individuals felt the initiatives were feasible and improved workflow, communication, and transparency. However, participants described future adaptations that would help improve this process including improved standardization, automation, and transparency.

Conclusion
The acceptability, adoption, and feasibility of two initiatives to improve the PA process within the one clinical site were well received but issues of generalizability limited the initiatives adoption system wide.
Involvement of immune system and Epithelial–Mesenchymal-Transition in increased invasiveness of clustered circulatory tumor cells in breast cancer
Authors: Khoshbakht Samane , Azimzadeh Jamalkandi Sadegh , Masudi-Nejad Ali 
Published: November 2021

Abstract
Background
Circulating tumor cells (CTCs) are the critical initiators of distant metastasis formation. In which, the reciprocal interplay among different metastatic pathways and their metastasis driver genes which promote survival of CTCs is not well introduced using network approaches.

Methods
Here, to investigate the unknown pathways of single/cluster CTCs, the co-expression network was reconstructed, using WGCNA (Weighted Correlation Network Analysis) method. Having used the hierarchical clustering, we detected the Immune-response and EMT subnetworks. The metastatic potential of genes was assessed and validated through the support vector machine (SVM), neural network, and decision tree methods on two external datasets. To identify the active signaling pathways in CTCs, we reconstructed a casual network. The Log-Rank test and Kaplan–Meier curve were applied to detect prognostic gene signatures for distant metastasis-free survival (DMFS). Finally, a predictive model was developed for metastasis risk of patients using VIF-stepwise feature selection.

Results
Our results showed the crosstalk among EMT, the immune system, menstrual cycles, and the stemness pathway in CTCs. In which, fluctuation of menstrual cycles is a new detected pathway in breast cancer CTCs. The reciprocal association between immune responses and EMT was identified in CTCs. The SVM model indicated a high metastatic potential of EMT subnetwork (accuracy, sensitivity, and specificity scores were 87%). The DMFS model was identified to predict patients’ metastasis risks. (c-index = 0.7). Finally, novel metastatic biomarkers of KRT18 and KRT19 were detected in breast cancer CTCs.

Conclusions
In conclusion, the reciprocal interplay among critical unknown pathways in CTCs manifests both their survival in blood and metastatic potentials. Such findings may help to develop more precise predictive metastatic-risk models or detect pivotal metastatic biomarkers.
Cytotoxicity of synthetic derivatives against breast cancer and multi-drug resistant breast cancer cell lines: a literature-based perspective study
Authors: Sharmin Shabnam , Rahaman Md. Mizanur , Martorell Miquel , Sastre-Serra Jorge , Sharifi-Rad Javad , Butnariu Monica , Bagiu Iulia Cristina , Bagiu Radu Vasile , Islam Mohammad Torequl 
Published: November 2021

AbstractCancer is the second most killer worldwide causing millions of people to lose their lives every year. In the case of women, breast cancer takes away the highest proportion of mortality rate than other cancers. Due to the mutation and resistance-building capacity of different breast cancer cell lines against conventional therapies, this death rate is on the verge of growth. New effective therapeutic compounds and treatment method is the best way to look out for in this critical time. For instance, new synthetic derivatives/ analogues synthesized from different compounds can be a ray of hope. Numerous synthetic compounds have been seen enhancing the apoptosis and autophagic pathway that directly exerts cytotoxicity towards different breast cancer cell lines. To cease the ever-growing resistance of multi-drug resistant cells against anti-breast cancer drugs (Doxorubicin, verapamil, tamoxifen) synthetic compounds may play a vital role by increasing effectivity, showing synergistic action. Many recent and previous studies have reported that synthetic derivatives hold potentials as an effective anti-breast cancer agent as they show great cytotoxicity towards cancer cells, thus can be used even vastly in the future in the field of breast cancer treatment. This review aims to identify the anti-breast cancer properties of several synthetic derivatives against different breast cancer and multi-drug-resistant breast cancer cell lines with their reported mechanism of action and effectivity.
Extracellular vesicles in malaria: an agglomeration of two decades of research
Authors: Opadokun Tosin , Rohrbach Petra 
Published: November 2021

AbstractMalaria is a complex parasitic disease, caused by Plasmodium spp. More than a century after the discovery of malaria parasites, this disease continues to pose a global public health problem and the pathogenesis of the severe forms of malaria remains incompletely understood. Extracellular vesicles (EVs), including exosomes and microvesicles, have been increasingly researched in the field of malaria in a bid to fill these knowledge gaps. EVs released from Plasmodium-infected red blood cells and other host cells during malaria infection are now believed to play key roles in disease pathogenesis and are suggested as vital components of the biology of Plasmodium spp. Malaria-derived EVs have been identified as potential disease biomarkers and therapeutic tools. In this review, key findings of malaria EV studies over the last 20 years are summarized and critically analysed. Outstanding areas of research into EV biology are identified. Unexplored EV research foci for the future that will contribute to consolidating the potential for EVs as agents in malaria prevention and control are proposed.
Adipose tissue alleviates the stress response by releasing adiponectin during laparoscopic surgery in patients with colorectal cancer
Authors: Shi Wenjiao , Lou Jian , Zhang Xiaodan , Ji Yun , Weng Xiaojian , Du Jianer 
Published: November 2021

Abstract
Background and objectives
Laparoscopic colorectal surgery causes a lower stress response than open surgery. Adiponectin is mainly derived from adipocytes and has antidiabetic, antioxidative, and anti-inflammatory capabilities. The objective of the present study was to investigate the protein expression of adiponectin in adipose tissue, and the serum levels of adiponectin, oxidative stress markers and proinflammatory factors during laparoscopic colorectal surgery and open surgery periods.

Methods
Forty patients aged 60 to 80, with American Society of Anesthesiologists (ASA) I ~ II who underwent radical resection of colorectal cancer were recruited to the study. Laparoscopic group and open group included 20 patients each. Mesenteric adipose tissue and venous blood before (T1) and at the end (T2) of surgery were collected to examine adiponectin levels, and venous blood was collected to examine serum levels of oxidative stress related markers (superoxide dismutase (SOD), glutathione (GSH), lipid peroxide (LPO), malondialdehyde (MDA)), and inflammation-related factors (interleukin (IL)-1β, interleukin (IL)-6, tumor necrosis factor-α (TNF-α)).

Results
Protein and serum levels of adiponectin were analyzed, and adiponectin levels were significantly increased at T2 than T1 in the laparoscopic surgery, while adiponectin levels were significantly higher in the laparoscopic surgery than in the open surgery at T2. In addition, the serum levels of SOD and GSH were significantly higher in the laparoscopic surgery than in open surgery at T2. However, the serum levels of LPO, TNF-α, IL-1β, and IL-6 were significantly lower in the laparoscopic group than in open group at T2.

Conclusion
Laparoscopic surgery induced higher levels of adiponectin in both adipose tissue and the bloodstream. Oxidative stress and the inflammatory response were lower during laparoscopic colorectal surgery than during conventional open surgery. These data suggest that adipose tissue may alleviate the stress response during laparoscopic surgery by releasing adiponectin in patients with colorectal cancer.
Practices and resilience of dieticians during the COVID-19 pandemic: a national survey in the United Arab Emirates
Authors: Naja Farah , Radwan Hadia , Cheikh Ismail Leila , Hashim Mona , Rida Wafaa Helmi , Abu Qiyas Salma , Bou-Karroum Karen , Alameddine Mohamad 
Published: November 2021

Abstract
Background
The COVID-19 pandemic impacted the practices and resilience of most healthcare workers, including dieticians. In addition to offering critical care to COVID-19 patients, dieticians play a major role in preventing and managing conditions known to affect COVID-19, such as obesity and metabolic disorders. The objective of this study was to examine the conditions and changes in the work environment as well as resilience and its correlates among dieticians during the COVID-19 pandemic in the United Arab Emirates (UAE).

Methods
A cross-sectional national survey was conducted among dieticians practicing in the UAE (n = 371), using a web-based questionnaire. The questionnaire addressed, in addition to the sociodemographic information, the practice-related characteristics and resilience of participants. For the latter the Connor–Davidson Resilience Scale© was used. Descriptive statistics as well as simple and multiple linear regressions were used in the statistical analysis.

Results
Of participants, 26.4% reported not having access to personal protective equipment and 50% indicated being concerned for their safety and health. Furthermore, considerable proportions of participants were not satisfied (45%) with the support nor with the appreciation (37.7%) they received during the pandemic. One in four dieticians considered quitting his/her job. While 65.8% of participants reported counseling COVID-19 patients, a third did not use any online platform for counseling. The most cited challenge to dietetic practice during the pandemic was ‘maintaining work-life balance’ (43.1%). The mean CD-RISC score was 72.0 ± 14.0. After adjustment, working in a hospital or public clinic (as opposed to private clinic), having a condition preventing face-to-face counseling, considering quitting job and feeling neutral or dissatisfied with the appreciation were associated with lower resilience scores, while counseling COVID-19 patients was associated with higher scores.

Conclusions
Despite the fairly high resilience among dieticians practicing in the UAE during the COVID-19 pandemic, the findings of this study highlighted a few challenges, mainly related to safe practice environment, support for online counseling, and maintaining work-life balance. Concerted efforts of policy and decision makers ought to develop targeted programs for dieticians to ensure their retention and wellbeing during the COVID-19 pandemic.
Behaviours that prompt primary school teachers to adopt and implement physically active learning: a meta synthesis of qualitative evidence
Authors: Daly-Smith Andrew , Morris Jade L. , Norris Emma , Williams Toni L. , Archbold Victoria , Kallio Jouni , Tammelin Tuija H. , Singh Amika , Mota Jorge , von Seelen Jesper , Pesce Caterina , Salmon Jo , McKay Heather , Bartholomew John , Resaland Geir Kare 
Published: November 2021

AbstractBackgroundPhysically active learning (PAL) - integration of movement within delivery of academic content - is a core component of many whole-of-school physical activity approaches. Yet, PAL intervention methods and strategies vary and frequently are not sustained beyond formal programmes. To improve PAL training, a more comprehensive understanding of the behavioural and psychological processes that influence teachers’ adoption and implementation of PAL is required. To address this, we conducted a meta-synthesis to synthesise key stakeholders’ knowledge of facilitators and barriers to teachers’ implementing PAL in schools to improve teacher-focussed PAL interventions in primary (elementary) schools.MethodologyWe conducted a meta-synthesis using a five-stage thematic synthesis approach to; develop a research purpose and aim, identify relevant articles, appraise studies for quality, develop descriptive themes and interpret and synthesise the literature. In the final stage, 14 domains from the Theoretical Domain Framework (TDF) were then aligned to the final analytical themes and subthemes.ResultsWe identified seven themes and 31 sub-themes from 25 eligible papers. Four themes summarised teacher-level factors: PAL benefits, teachers’ beliefs about own capabilities, PAL teacher training, PAL delivery. One theme encompassed teacher and school-level factors: resources. Two themes reflected school and external factors that influence teachers’ PAL behaviour: whole-school approach, external factors. Ten (of 14) TDF domains aligned with main themes and sub-themes:Knowledge, Skills, Social/Professional Role and Identity, Beliefs about Capabilities, Beliefs about Consequences, Reinforcement, Goals, Environmental Context and Resources, Social influencesandEmotion.ConclusionsOur synthesis illustrates the inherent complexity required to change and sustain teachers’ PAL behaviours. Initially, teachers must receive the training, resources and support to develop the capability to implement and adapt PAL. The PAL training programme should progress as teachers’ build their experience and capability; content should be ‘refreshed’ and become more challenging over time. Subsequently, it is imperative to engage all levels of the school community for PAL to be fully integrated into a broader school system. Adequate resources, strong leadership and governance, an engaged activated community and political will are necessary to achieve this, and may not currently exist in most schools.
Prostaglandin EP2 receptor antagonist ameliorates neuroinflammation in a two-hit mouse model of Alzheimer’s disease
Authors: Banik Avijit , Amaradhi Radhika , Lee Daniel , Sau Michael , Wang Wenyi , Dingledine Raymond , Ganesh Thota 
Published: November 2021

Abstract
Background
Alzheimer’s disease (AD) causes substantial medical and societal burden with no therapies ameliorating cognitive deficits. Centralized pathologies involving amyloids, neurofibrillary tangles, and neuroinflammatory pathways are being investigated to identify disease-modifying targets for AD. Cyclooxygenase-2 (COX-2) is one of the potential neuroinflammatory agents involved in AD progression. However, chronic use of COX-2 inhibitors in patients produced adverse cardiovascular effects. We asked whether inhibition of EP2 receptors, downstream of the COX-2 signaling pathway, can ameliorate neuroinflammation in AD brains in presence or absence of a secondary inflammatory stimuli.

Methods
We treated 5xFAD mice and their non-transgenic (nTg) littermates in presence or absence of lipopolysaccharide (LPS) with an EP2 antagonist (TG11-77.HCl). In cohort 1, nTg (no-hit) or 5xFAD (single-hit—genetic) mice were treated with vehicle or TG11-77.HCl for 12 weeks. In cohort 2, nTg (single-hit—environmental) and 5xFAD mice (two-hit) were administered LPS (0.5 mg/kg/week) and treated with vehicle or TG11-77.HCl for 8 weeks.

Results
Complete blood count analysis showed that LPS induced anemia of inflammation in both groups in cohort 2. There was no adverse effect of LPS or EP2 antagonist on body weight throughout the treatment. In the neocortex isolated from the two-hit cohort of females, but not males, the elevated mRNA levels of proinflammatory mediators (IL-1β, TNF, IL-6, CCL2, EP2), glial markers (IBA1, GFAP, CD11b, S110B), and glial proteins were significantly reduced by EP2 antagonist treatment. Intriguingly, the EP2 antagonist had no effect on either of the single-hit cohorts. There was a modest increase in amyloid–plaque deposition upon EP2 antagonist treatment in the two-hit female brains, but not in the single-hit genetic female cohort.

Conclusion
These results reveal a potential neuroinflammatory role for EP2 in the two-hit 5xFAD mouse model. A selective EP2 antagonist reduces inflammation only in female AD mice subjected to a second inflammatory insult.
Market viability: a neglected concept in implementation science
Authors: Proctor Enola K. , Toker Emre , Tabak Rachel , McKay Virginia R. , Hooley Cole , Evanoff Bradley 
Published: November 2021

AbstractThis debate paper asserts that implementation science needs to incorporate a key concept from entrepreneurship—market demand—and demonstrates how assessing an innovation’s potential market viability might advance the pace and success of innovation adoption and sustainment. We describe key concepts, language distinctions, and questions that entrepreneurs pose to implementation scientists—many of which implementation scientists appear ill-equipped to answer. The paper concludes with recommendations about how concepts from entrepreneurship, notably market viability assessment, can enhance the translation of research discoveries into real-world adoption, sustained use, and population health benefits. The paper further proposes activities that can advance implementation science’s capacity to draw from the field of entrepreneurship, along with the data foundations required to assess and cultivate market demand.
Effectiveness of convalescent plasma therapy in eight non-intubated coronavirus disease 2019 patients in Indonesia: a case series
Authors: Rahardjo Theresia Monica , Yogipranata Elizabeth , Naswan Ardian Hediyanto , Sari Fitri Rahayu , Budiono Fajar , Permatasari Hernawati , Chuntari C. H. R. Driantik 
Published: November 2021

Abstract
Background
Severe acute respiratory syndrome coronavirus 2, the cause of coronavirus disease 2019, has become a global pandemic. Currently, there is no definitive treatment for coronavirus disease 2019. Convalescent plasma therapy has become a potential specific curative method, while vaccines as protection modalities require further work.

Case presentation
Eight non-intubated Indonesian patients, ages ranging from 40 to 74 years old, with coronavirus disease 2019 confirmed by viral Ribonucleid Acid (RNA) real-time polymerase chain reaction tests were included. Four patients were administered two doses of 200 mL convalescent plasma, and the other four patients were administered one dose of convalescent plasma with an antibody titer of 1:320, within the first 14 days since symptoms occurred. The median times from illness onset to convalescent plasma therapy and from the first day of hospital admission to convalescent plasma therapy were 13 and 6.5 days, respectively. All patients showed improvements in clinical symptoms, laboratory parameters, thorax imaging, negative conversion of polymerase chain reaction results, and decreased oxygen supplementation within 1 week after convalescent plasma therapy. Patients with two convalescent plasma doses tended to have faster recovery than those with one convalescent plasma dose. No severe adverse effects were observed in any patient.

Conclusion
This is the first case series in Indonesia showing that convalescent plasma therapy is safe and well tolerated and that early convalescent plasma therapy before the patient is intubated could potentially prevent disease progression, increase the recovery rate, and shorten the inpatient time of stay.
Identification of a novel immunological epitope on Hexon of fowl adenovirus serotype 4
Authors: Liu Jingyi , Mei Nan , Wang Yaling , Shi Xinjin , Chen Hongjun 
Published: November 2021

AbstractFowl adenovirus serotype 4 (FAdV-4), the causative agent of hepatitis-hydropericardium syndrome (HHS), distributed widely in the poultry farms in China. Hexon is one of the major capsid proteins associated with viral species or serotypes. However, the epitopes of Hexon protein remain largely unknown. In this study, a monoclonal antibody (mAb) specific to Hexon protein of FAdV-4, designated as 3G8, was generated. Subsequently, the linear peptide recognized by 3G8 was mapped and identified as 213AYGAYVK219 using a series of overlapping peptides generated from Hexon protein. Amino acid sequence analysis revealed that the epitope recognized by 3G8 was highly conserved across all the FAdVs. The epitope was immunogenic and could be recognized by FAdV-4 positive chicken serum samples. These findings will enrich our knowledge regarding the epitope on Hexon and provide valuable information for further characterization of the antigenicity of Hexon protein.
On Glassey’s conjecture for semilinear wave equations in Friedmann–Lemaître–Robertson–Walker spacetime
Authors: Tsutaya Kimitoshi , Wakasugi Yuta 
Published: November 2021

AbstractConsider nonlinear wave equations in the spatially flat Friedmann–Lemaître–Robertson–Walker (FLRW) spacetimes. We show blow-up in finite time of solutions and upper bounds of the lifespan of blow-up solutions to give the FLRW spacetime version of Glassey’s conjecture for the time derivative nonlinearity. We also show blow-up results for the space derivative nonlinear term.