bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing physician participation as subjects in scientific and quality improvement research
Authors: Hysong Sylvia J. , McGuire Amy L. 
Published: August 2022

Abstract
Background
The twenty-first century has witnessed an exponential increase in healthcare quality research. As such activities become more prevalent, physicians are increasingly needed to participate as subjects in research and quality improvement (QI) projects. This raises an important ethical question: how should physicians be remunerated for participating as research and/or QI subjects?

Financial versus non-monetary incentives for participation
Research suggests participation in research and QI is often driven by conditional altruism, the idea that although initial interest in enrolling in research is altruistic or prosocial, decisions to actually perform study tasks are cost–benefit driven. Thus, the three models commonly employed to appropriately compensate participants (in-kind compensation such as travel reimbursement, paying market rates for the subject’s time, and paying market rates for the activity asked of the participant) are a poor fit when the participant is a clinician, largely due to the asymmetry between cost and benefit or value to the participant. Non-monetary alternatives such as protected time for participation, continuing education or maintenance of certification credit, or professional development materials, can provide viable avenues for reducing this asymmetry.

Conclusion
Research and QI are integral to the betterment of medicine and healthcare. To increase physician participation in these activities as the subject of study, new models are needed that clarify the physician’s role in research and QI as a subject. Non-monetary approaches are recommended to successfully and ethically encourage research and QI participation, and thus incorporate these activities as a normal part of the ethical clinician’s and successful learning healthcare system’s world view.
Human-centered design of clinical decision support for management of hypertension with chronic kidney disease
Authors: Garabedian Pamela M. , Gannon Michael P. , Aaron Skye , Wu Edward , Burns Zoe , Samal Lipika 
Published: August 2022

Abstract
Background
Primary care providers face challenges in recognizing and controlling hypertension in patients with chronic kidney disease (CKD). Clinical decision support (CDS) has the potential to aid clinicians in identifying patients who could benefit from medication changes. This study designed an alert to control hypertension in CKD patients using an iterative human-centered design process.

Methods
In this study, we present a human-centered design process employing multiple methods for gathering user requirements and feedback on design and usability. Initially, we conducted contextual inquiry sessions to gather user requirements for the CDS. This was followed by group design sessions and one-on-one formative think-aloud sessions to validate requirements, obtain feedback on the design and layout, uncover usability issues, and validate changes.

Results
This study included 20 participants. The contextual inquiry produced 10 user requirements which influenced the initial alert design. The group design sessions revealed issues related to several themes, including recommendations and clinical content that did not match providers' expectations and extraneous information on the alerts that did not provide value. Findings from the individual think-aloud sessions revealed that participants disagreed with some recommended clinical actions, requested additional information, and had concerns about the placement in their workflow. Following each step, iterative changes were made to the alert content and design.

Discussion
This study showed that participation from users throughout the design process can lead to a better understanding of user requirements and optimal design, even within the constraints of an EHR alerting system. While raising awareness of design needs, it also revealed concerns related to workflow, understandability, and relevance.

Conclusion
The human-centered design framework using multiple methods for CDS development informed the creation of an alert to assist in the treatment and recognition of hypertension in patients with CKD.
Fuzzy constraint-based agent negotiation framework for doctor-patient shared decision-making
Authors: Lin Kaibiao , Liu Yong , Lu Ping , Yang Yimin , Fan Haiting , Hong Feiping 
Published: August 2022

AbstractBackgroundThe clinical practice of shared decision-making (SDM) has grown in importance. However, most studies on SDM practice concentrated on providing auxiliary knowledge from the third-party standpoint without consideration for the value preferences of doctors and patients. The essences of these methods are complete and manual negotiation, and the problems of high cost, time consumption, delayed response, and decision fatigue are serious.MethodsIn response to the above limitations, this article proposes a fuzzy constraint-directed agent-based negotiation and recommendation framework for bilateral and multi-issue preference negotiation in SDM (PN-SDM). Its purpose is to provide preference information and intellectualize PN-SDM to promote SDM practice. We modeled PN-SDM problems as distributed fuzzy constraint satisfaction problems and designed the doctor agent and patient agent to negotiate on behalf of the doctor and patient. The negotiation result was then transformed into treatment plans by the recommendation model. The proposed negotiation and recommendation models were introduced in detail by an instance.ResultsThe proposed method with different strategies and negotiation pairs achieves good performance in terms of negotiation running time, negotiation rounds, and combined aggregated satisfaction value. Specifically, it can feasibly and effectively complete multiple rounds of PN-SDM in a few seconds and obtain higher satisfaction.ConclusionThe experimental results indicate that the negotiation model can effectively simulate preference negotiation and relieve the pressure of increasing issues. The recommendation model can assist in decision-making and help to realize SDM. In addition, it can flexibly cope with various negotiation scenarios by using different negotiation strategies (e.g., collaborative, win–win, and competitive).
Implementation of a telemedicine, stroke evaluation service; a qualitative study
Authors: Kjelle Elin , Myklebust Aud Mette 
Published: August 2022

Abstract
Background
Acute ischemic stroke requires early medical imaging with a computed tomography (CT) scan and immediate thrombolysis treatment. In rural areas, the long distance to the nearest hospital reduce the patients’ probability of receiving medical assistance within the 4.5-h period. The aim of this study was to assess how the service was set-up, and how managers and personnel experience the organisation and value of a rural telemedicine, remote controlled CT stroke service.

Methods
Ten semi-structured individual interviews and one semi-structured focus group interview were conducted. The sample included 15 participants involved in the telemedicine service in Hallingdal, Norway. The interview guide consisted of questions on the service, experience of working with the service, value and quality, management, and challenges. Interviews were recorded and transcribed verbatim. Thematic content analysis was used to develop a narrative of the findings.

Results
Findings were categorised into three main categories; value of the service, organisation of the project, and from project to permanent service. Participants perceived the service to be valuable for patients and the local community. The service included task shifting from radiographers and junior doctors to the local paramedics. To enable long- term operation of the service the participants suggested management, coordination, and continuous training as important factors.

Conclusions
The service was perceived as valuable to the local community, providing a sense of healthcare security and equitability. Management’s involvement, flexibility, and coordination appears to be a key factor for successful implementation and long-term sustainability of the service.
Selenium and/or vitamin E upregulate the antioxidant gene expression and parameters in broilers
Authors: Elgendey Fatma , Al Wakeel Rasha A. , Hemeda Shabaan A. , Elshwash Aya Mohamed , Fadl Sabreen E. , Abdelazim Aaser M. , Alhujaily Muhanad , Khalifa Olla A. 
Published: August 2022

Abstract
Background
In contrast to free radicals, the first line of protection is assumed to be vitamin E and selenium. The present protocol was designed to assess the roles of vitamin E and/or a selenium-rich diet that affected the blood iron and copper concentrations, liver tissue antioxidant and lipid peroxidation, and gene expression linked to antioxidants in the liver tissue of broilers. The young birds were classified according to the dietary supplement into four groups; control, vitamin E (100 mg Vitamin/kg diet), selenium (0.3 mg sodium selenite/kg diet), and vitamin E pulse selenium (100 mg vitamin/kg diet with 0.3 mg sodium selenite/kg diet) group.

Results
The results of this experiment suggested that the addition of vitamin E with selenium in the broiler diet significantly increased (P ≤ 0.05) serum iron when compared with the other groups and serum copper when compared with the vitamin E group. Moreover, the supplements (vitamin E or vitamin E with selenium) positively affected the enzymatic activity of the antioxidant-related enzymes with decreased malondialdehyde (MDA),which represents lipid peroxidation in broiler liver tissue. Moreover, the two supplements significantly upregulated genes expression related to antioxidants.

Conclusion
Therefore, vitamin E and/or selenium can not only act as exogenous antioxidants to prevent oxidative damage by scavenging free radicals and superoxide, but also act as gene regulators, regulating the expression of endogenous antioxidant enzymes.
A first report on the efficacy of a single intra-articular administration of blood cell secretome, triamcinolone acetonide, and the combination of both in dogs with osteoarthritis
Authors: Alves J. C. , Santos A. , Jorge P. , Carreira L. Miguel 
Published: August 2022

AbstractBackgroundOsteoarthritis represents a significant welfare problem for many dogs, with limited therapeutic options other than palliative pain control. To evaluate the effect of the intra-articular administration of blood cell secretome and triamcinolone, 15 dogs with bilateral hip osteoarthritis were randomly assigned to a blood cell secretome (BCSG,n = 5), triamcinolone (TG) or their combination group (BCS + TG,n = 5). BCSG received a single intra-articular administration of 3 ml of blood cell secretome, TG 0.5 ml of triamcinolone acetonide 40 mg/ml, and BCS + TG received the combined products. The volume to administrate was corrected to 3.5 ml with saline. On days 0, 8, 15, 30, 60, 90, 120, 150, and 180, a copy of the Canine Brief Pain Inventory (divided into pain interference score—PIS and Pain Severity Score—PSS), Liverpool Osteoarthritis in Dogs (LOAD), Hudson Visual Analogue Scale (HVAS), and Canine Orthopedic Index (COI, divided into function, gait, stiffness, and quality of life) was completed. Results were analyzed with the Kruskal–Wallis test and the Kaplan–Meier estimators were conducted and compared with the Log Rank test,p < 0.05.ResultsAnimals in the sample had a mean age of 9.0 ± 2.9 years and a bodyweight of 28.8 ± 4.1 kg. Hips were classified as moderate (8) and severe (7) osteoarthritis. No differences were found between groups at T0 regarding considered evaluations. Significant differences were observed between groups in pain scores from + 8d- + 150d, with BCS + TG exhibiting better results. The same was observed for HVAS and LOAD, from + 8d- + 120d. Improvements were also observed in several dimensions of the COI. Kaplan–Meier estimators showed that BCS + TG produced longer periods with better results, followed by BCSG and TG.ConclusionThe intra-articular administration of blood cell secretome improved the clinical signs and scores of several clinical metrology instruments in dogs with hip OA, particularly when combined with triamcinolone. Further studies are required.
Functional and structural characteristics of HLA-B*13:01-mediated specific T cells reaction in dapsone-induced drug hypersensitivity
Authors: Jiang Haiqin , Wang Chuang-Wei , Wang Zhaoxi , Dai Yufei , Zhu Yanping , Lee Yun-Shien , Cao Yang , Chung Wen-Hung , Ouyang Songying , Wang Hongsheng 
Published: August 2022

AbstractBackgroundSevere cutaneous adverse drug reactions (SCARs) are a group of serious clinical conditions caused by immune reaction to certain drugs. The allelic variance of human leukocyte antigens of HLA-B*13:01 has been strongly associated with hypersensitivities induced by dapsone (DDS). T-cell receptor mediated activation of cytotoxic T lymphocytes (CTLs) has also been suggested to play an essential role in pathogenesis of SCARs. However, HLA-B*13:01-DDS-TCR immune synapse that plays role in drug-induced hypersensitivity syndrome (DIHS) associated T cells activation remains uncharacterized.MethodsTo investigate the molecular mechanisms for HLA-B*13:01 in the pathogenesis of Dapsone-induced drug hypersensitivity (DDS-DIHS), we performed crystallization and expanded drug-specific CTLs to analyze the pathological role of DDS-DIHS.ResultsResults showed the crystal structure of HLA-B*13:01-beta-2-microglobulin (β2M) complex at 1.5 Å resolution and performed mutation assays demonstrating that I118 or I119, and R121 of HLA-B*13:01 were the key residues that mediate the binding of DDS. Subsequent single-cell TCR and RNA sequencing indicated that TCRs composed of paired TRAV12-3/TRBV28 clonotype with shared CDR3 region specifically recognize HLA-B*13:01-DDS complex to trigger inflammatory cytokines associated with DDS-DIHS.ConclusionOur study identified the novel p-i-HLA/TCR as the model of interaction between HLA-B*13:01, DDS and the clonotype-specific TCR in DDS-DIHS.Graphical Abstract
Upregulating carnitine palmitoyltransferase 1 attenuates hyperoxia-induced endothelial cell dysfunction and persistent lung injury
Authors: Chang Jason L. , Gong Jiannan , Rizal Salu , Peterson Abigail L. , Chang Julia , Yao Chenrui , Dennery Phyllis A. , Yao Hongwei 
Published: August 2022

Abstract
Background
Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants that may cause long-term lung dysfunction. Accumulating evidence supports the vascular hypothesis of BPD, in which lung endothelial cell dysfunction drives this disease. We recently reported that endothelial carnitine palmitoyltransferase 1a (Cpt1a) is reduced by hyperoxia, and that endothelial cell-specific Cpt1a knockout mice are more susceptible to developing hyperoxia-induced injury than wild type mice. Whether Cpt1a upregulation attenuates hyperoxia-induced endothelial cell dysfunction and lung injury remains unknown. We hypothesized that upregulation of Cpt1a by baicalin or l-carnitine ameliorates hyperoxia-induced endothelial cell dysfunction and persistent lung injury.

Methods
Lung endothelial cells or newborn mice (< 12 h old) were treated with baicalin or l-carnitine after hyperoxia (50% and 95% O2) followed by air recovery.

Results
We found that incubation with l-carnitine (40 and 80 mg/L) and baicalin (22.5 and 45 mg/L) reduced hyperoxia-induced apoptosis, impaired cell migration and angiogenesis in cultured lung endothelial cells. This was associated with increased Cpt1a gene expression. In mice, neonatal hyperoxia caused persistent alveolar and vascular simplification in a concentration-dependent manner. Treatment with l-carnitine (150 and 300 mg/kg) and baicalin (50 and 100 mg/kg) attenuated neonatal hyperoxia-induced alveolar and vascular simplification in adult mice. These effects were diminished in endothelial cell-specific Cpt1a knockout mice.

Conclusions
Upregulating Cpt1a by baicalin or l-carnitine ameliorates hyperoxia-induced lung endothelial cell dysfunction, and persistent alveolar and vascular simplification. These findings provide potential therapeutic avenues for using l-carnitine and baicalin as Cpt1a upregulators to prevent persistent lung injury in premature infants with BPD.
Ethanol yield improvement in Saccharomyces cerevisiae GPD2 Delta FPS1 Delta ADH2 Delta DLD3 Delta mutant and molecular mechanism exploration based on the metabolic flux and transcriptomics approaches
Authors: Yang Peizhou , Jiang Shuying , Lu Shuhua , Jiang Suwei , Jiang Shaotong , Deng Yanhong , Lu Jiuling , Wang Hu , Zhou Yong 
Published: August 2022

Abstract
Background
Saccharomyces cerevisiae generally consumes glucose to produce ethanol accompanied by the main by-products of glycerol, acetic acid, and lactic acid. The minimization of the formation of by-products in S. cerevisiae was an effective way to improve the economic viability of the bioethanol industry. In this study, S. cerevisiae GPD2, FPS1, ADH2, and DLD3 genes were knocked out by the Clustered Regularly Interspaced Short Palindromic Repeats Cas9 (CRISPR-Cas9) approach. The mechanism of gene deletion affecting ethanol metabolism was further elucidated based on metabolic flux and transcriptomics approaches.

Results
The engineered S. cerevisiae with gene deletion of GPD2, FPS1, ADH2, and DLD3 was constructed by the CRISPR-Cas9 approach. The ethanol content of engineered S. cerevisiae GPD2 Delta FPS1 Delta ADH2 Delta DLD3 Delta increased by 18.58% with the decrease of glycerol, acetic acid, and lactic acid contents by 22.32, 8.87, and 16.82%, respectively. The metabolic flux analysis indicated that the carbon flux rethanol in engineered strain increased from 60.969 to 63.379. The sequencing-based RNA-Seq transcriptomics represented 472 differential expression genes (DEGs) were identified in engineered S. cerevisiae, in which 195 and 277 genes were significantly up-regulated and down-regulated, respectively. The enriched pathways of up-regulated genes were mainly involved in the energy metabolism of carbohydrates, while the down-regulated genes were mainly enriched in acid metabolic pathways.

Conclusions
The yield of ethanol in engineered S. cerevisiae increased with the decrease of the by-products including glycerol, acetic acid, and lactic acid. The deletion of genes GPD2, FPS1, ADH2, and DLD3 resulted in the redirection of carbon flux.
Cheese whey supports high riboflavin synthesis by the engineered strains of the flavinogenic yeast Candida famata
Authors: Ruchala Justyna , Andreieva Yuliia A. , Tsyrulnyk Andriy O. , Sobchuk Svitlana M. , Najdecka Alicja , Wen Liu , Kang Yingqian , Dmytruk Olena V. , Dmytruk Kostyantyn V. , Fedorovych Dariya V. , Sibirny Andriy A. 
Published: August 2022

Abstract
Background
Riboflavin is a precursor of FMN and FAD which act as coenzymes of numerous enzymes. Riboflavin is an important biotechnological commodity with annual market sales exceeding nine billion US dollars. It is used primarily as a component of feed premixes, a food colorant, a component of multivitamin mixtures and medicines. Currently, industrial riboflavin production uses the bacterium, Bacillus subtilis, and the filamentous fungus, Ashbya gossypii, and utilizes glucose and/or oils as carbon substrates.

Results
We studied riboflavin biosynthesis in the flavinogenic yeast Candida famata that is a genetically stable riboflavin overproducer. Here it was found that the wild type C. famata is characterized by robust growth on lactose and cheese whey and the engineered strains also overproduce riboflavin on whey. The riboflavin synthesis on whey was close to that obtained on glucose. To further enhance riboflavin production on whey, the gene of the transcription activator SEF1 was expressed under control of the lactose-induced promoter of the native β-galactosidase gene LAC4. These transformants produced elevated amounts of riboflavin on lactose and especially on whey. The strain with additional overexpression of gene RIB6 involved in conversion of ribulose-5-phosphate to riboflavin precursor had the highest titer of accumulated riboflavin in flasks during cultivation on whey. Activation of riboflavin synthesis was also obtained after overexpression of the GND1 gene that is involved in the synthesis of the riboflavin precursor ribulose-5-phosphate. The best engineered strains accumulated 2.5 g of riboflavin/L on whey supplemented only with (NH4)2SO4 during batch cultivation in bioreactor with high yield (more than 300 mg/g dry cell weight). The use of concentrated whey inhibited growth of wild-type and engineered strains of C. famata, so the mutants tolerant to concentrated whey were isolated.

Conclusions
Our data show that the waste of dairy industry is a promising substrate for riboflavin production by C. famata. Possibilities for using the engineered strains of C. famata to produce high-value commodity (riboflavin) from whey are discussed.
Potential of antibody–drug conjugates (ADCs) for cancer therapy
Authors: Marei Hany E. , Cenciarelli Carlo , Hasan Anwarul 
Published: August 2022

AbstractThe primary purpose of ADCs is to increase the efficacy of anticancer medications by minimizing systemic drug distribution and targeting specific cells. Antibody conjugates (ADCs) have changed the way cancer is treated. However, because only a tiny fraction of patients experienced long-term advantages, current cancer preclinical and clinical research has been focused on combination trials. The complex interaction of ADCs with the tumor and its microenvironment appear to be reliant on the efficacy of a certain ADC, all of which have significant therapeutic consequences. Several clinical trials in various tumor types are now underway to examine the potential ADC therapy, based on encouraging preclinical results. This review tackles the potential use of ADCs in cancer therapy, emphasizing the essential processes underlying their positive therapeutic impacts on solid and hematological malignancies. Additionally, opportunities are explored to understand the mechanisms of ADCs action, the mechanism of resistance against ADCs, and how to overcome potential resistance following ADCs administration. Recent clinical findings have aroused interest, leading to a large increase in the number of ADCs in clinical trials. The rationale behind ADCs, as well as their primary features and recent research breakthroughs, will be discussed. We then offer an approach for maximizing the potential value that ADCs can bring to cancer patients by highlighting key ideas and distinct strategies.