bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of the QX002N anti-IL-17 Monoclonal Antibody: A Phase I, Randomized, Double-Blind, Single Ascending Dose Study in Healthy Chinese Volunteers
Authors: Wu Min , Zhang Hong , Li Qianqian , Chen Hong , Fang Min , Yang Lizhi , Ding Yanhua 
Published: March 2022

Background: The innovative injection of interleukin 17 A (IL-17A) monoclonal antibody QX002N is being developed to treat active ankylosing spondylitis and plaque psoriasis in adults.Objective: This study investigated the pharmacokinetics (PKs), pharmacodynamics (PDs) safety, tolerability, and immunogenicity of single ascending subcutaneous injections of QX002N in healthy Chinese volunteers.Methods: A total of 65 healthy subjects were enrolled in a randomized, double-blind, placebo-controlled, single ascending dose phase I study (10–320 mg). Ten subjects were allocated to each cohort (containing 8 subjects treated with QX002N and 2 with placebo), except cohort 1 (only 4 subjects treated with QX002N and 1 with placebo). The studies on PKs, PDs, tolerability, and immunogenicity of QX002N were performed.Results: Our study showed that QX002N injection was well tolerated, without deaths, serious adverse events, or discontinuations due to treatment-emergent adverse events (TEAEs). Neither more frequency nor high severity of the drug-related adverse reaction was observed with increasing QX002N dose. The TEAEs in all subjects were considered Grades 1–2 (CTCAE 5.0) except for one case of Grade 3 (hypertriglyceridemia). Tmax of QX002N was obtained from 168 to 240 h across the dose range after administration. The Cmax and area under the curve of QX002N increased in proportion to dose, and showed linear PKs. Anti-drug antibody positivity was detected in one (1.9%) subject after drug administration.Conclusion: QX002N was well tolerated in our study. Based on the PKs and safety results of QX002N, 80 mg is recommended as the effective dose for a future phase Ib study.Clinical Trial Registration: https://www.chinadrugtrials.org.cn/, identifier ChiCTR1900023040.
Effectiveness and Safety Analysis of PIs/r Based Dual Therapy in Treatment-Naïve, HIV/AIDS Patients: A Network Meta Analysis of Randomized Controlled Trials
Authors: Hui Liu , Xiaoxu Han , Yuqi Wang , Peng Wang , Xin Wang , Yunyun Yi , Xin Li 
Published: March 2022

Background: Dual anti-retroviral therapy is the main proven valuable intervention type for treating naïve HIV/AIDS. Currently, no high-quality evidence is available regarding the best dual schemes.Objectives: The aim of this study is to evaluate the effectiveness and safety of PIs/r-based dual therapy in treatment-naïve HIV/AIDS patients by using network meta-analysis.Methods: Randomized controlled trials of PIs/r-based dual therapy in treatment-naïve HIV/AIDS were searched based on Embase, PubMed and Cochrane library database from January 2006 to June 2021. Taking viral suppression rate, CD4+T cell count changes from baseline as the primary indicator and adverse events rate as secondary indicator, the network meta-analysis was performed on Review Manager and STATA software. Heterogeneity was assessed by the Q statistic and I2. We registered our protocol in Prospero with ID CRD42021275466.Results: Among 15 randomized controlled trials (3,497 patients and 7 PIs/r-based dual therapy) were reviewed in this study. According to the forest map, DRV/r + INSTIs was more effective compared to triple therapy (TT) in viral suppression [OR 0.82, 95% CI (0.61–1.11)], in CD4+T cell count changes from baseline [MD 1.9, 95% CI (0.7, 3.1), I2 86%], in adverse events [OR 0.98, 95% CI (0.68–1.39)]. Furthermore, SUCRA ranking analysis indicated that DRV/r + INSTIs was superior to TT in viral suppression (DRV/r + INSTIs 75.5% &gt; TT 41.2%) and in immune construction (DRV/r + INSTIs 67% &gt; TT 42%). In addition, DRV/r + INSTIs was similar to TT in adverse events (DRV/r + INSTIs 54.9% ≈ TT 54.7%).Conclusion: DRV/r + INSTIs was obviously superior to TT in viral suppression and immune reconstruction, and was not higher than TT in adverse events.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42021275466
Title: Understanding a Low Vitamin D State in the Context of COVID-19
Authors: Walsh James Bernard , McCartney Daniel M. , Laird Éamon , McCarroll Kevin , Byrne Declan G. , Healy Martin , O’Shea Paula M. , Kenny Rose Anne , Faul John L. 
Published: March 2022

While a low vitamin D state has been associated with an increased risk of infection by SARS-CoV-2 in addition to an increased severity of COVID-19 disease, a causal role is not yet established. Here, we review the evidence relating to i) vitamin D and its role in SARS-CoV-2 infection and COVID-19 disease ii) the vitamin D status in the Irish adult population iii) the use of supplemental vitamin D to treat a deficient status and iv) the application of the Bradford-Hill causation criteria. We conclude that reverse causality probably makes a minimal contribution to the presence of low vitamin D states in the setting of COVID-19. Applying the Bradford-Hill criteria, however, the collective literature supports a causal association between low vitamin D status, SARS-CoV-2 infection, and severe COVID-19 (respiratory failure, requirement for ventilation and mortality). A biologically plausible rationale exists for these findings, given vitamin D’s role in immune regulation. The thresholds which define low, deficient, and replete vitamin D states vary according to the disease studied, underscoring the complexities for determining the goals for supplementation. All are currently unknown in the setting of COVID-19. The design of vitamin D randomised controlled trials is notoriously problematic and these trials commonly fail for a number of behavioural and methodological reasons. In Ireland, as in most other countries, low vitamin D status is common in older adults, adults in institutions, and with obesity, dark skin, low UVB exposure, diabetes and low socio-economic status. Physiological vitamin D levels for optimal immune function are considerably higher than those that can be achieved from food and sunlight exposure alone in Ireland. A window exists in which a significant number of adults could benefit from vitamin D supplementation, not least because of recent data demonstrating an association between vitamin D status and COVID-19. During the COVID pandemic, we believe that supplementation with 20-25ug (800–1000 IU)/day or more may be required for adults with apparently normal immune systems to improve immunity against SARS-CoV-2. We expect that higher monitored doses of 37.5–50 ug (1,500–2,000)/day may be needed for vulnerable groups (e.g., those with obesity, darker skin, diabetes mellitus and older adults). Such doses are within the safe daily intakes cited by international advisory agencies.
Cholesterol Sulfate Exerts Protective Effect on Pancreatic β-Cells by Regulating β-Cell Mass and Insulin Secretion
Authors: Zhang Xueping , Deng Dan , Cui Daxin , Liu Yin , He Siyuan , Zhang Hongmei , Xie Yaorui , Yu Xiaoqian , Yang Shanshan , Chen Yulong , Su Zhiguang 
Published: March 2022

Rational: Cholesterol sulfate (CS) is the most abundant known sterol sulfate in human plasma, and it plays a significant role in the control of metabolism and inflammatory response, which contribute to the pathogenesis of insulin resistance, β-cell dysfunction and the resultant development of diabetes. However, the role of CS in β-cells and its effect on the development of diabetes remain unknown. Here, we determined the physiological function of CS in pancreatic β-cell homeostasis.Materials and Methods: Blood CS levels in streptozotocin (STZ)- or high-fat diet-induced diabetic mice and patients with type 1 or 2 diabetes were determined by LC-MS/MS. The impact of CS on β-cell mass and insulin secretion was investigated in vitro in isolated mouse islets and the β-cell line INS-1 and in vivo in STZ-induced diabetic mice. The molecular mechanism of CS was explored by viability assay, EdU incorporation analysis, flow cytometry, intracellular Ca2+ influx analysis, mitochondrial membrane potential and cellular ROS assays, and metabolism assay kits.Results: Plasma CS levels in mice and humans were significantly elevated under diabetic conditions. CS attenuated diabetes in a low-dose STZ-induced mouse model. Mechanistically, CS promoted β-cell proliferation and protected β-cells against apoptosis under stressful conditions, which in turn preserved β-cell mass. In addition, CS supported glucose transporter-2 (GLUT2) expression and mitochondrial integrity, which then resulted in a less reactive oxygen species (ROS) generation and an increase in ATP production, thereby enabling insulin secretion machinery in the islets to function adequately.Conclusion: This study revealed a novel dual role of CS in integrating β-cell survival and cell function, suggesting that CS might offer a physiologic approach to preserve β-cells and protect against the development of diabetes mellitus.
Non-Uniform Self-Gating in 2D Lung Imaging
Authors: Metze Patrick , Frantz Hanna , Straubmüller Fabian , Speidel Tobias , Stumpf Kilian , Beer Meinrad , Rottbauer Wolfgang , Rasche Volker 
Published: March 2022

Purpose: To adapt the non-uniform Self-Gating (nuSG) method and compare it to established self-gating approaches for lung imaging in uniform and highly irregular respiratory patterns.Methods: Six healthy volunteers underwent free breathing lung MRI using a radial tiny golden angle ultrashort echo-time sequence. Acquisitions were performed with the volunteer breathing as uniformly as possible and with a deliberately non-uniform respiratory pattern. The acquired data was reconstructed with the nuSG method, previously introduced for cardiac imaging and imaging of the temporomandibular joint (TMJ) and compared to established k-space based and image-based self-gating approaches. Residual motion blur, SNR and functional values were assessed and compared to reference breath-hold acquisitions.Results: nuSG is capable of reconstructing high-quality images for uniform and non-uniform breathing patterns and is furthermore capable of resolving motion in cases where additional motion is superimposed or no clear motion surrogate exists. Derived functional values do not differ significantly from other image-based gated reconstructions - and in the case of non-uniform respiratory patterns replicate the reference BH values.Conclusion: Image based approaches are computationally more demanding but yield better results in all aspects. In scenarios with a direct surrogate for respiratory motion (i.e. the lung-liver interface) the extraction of a one-dimensional navigator is sufficient. When there is no direct surrogate for the motion of the target structure available (e.g., considerable through-plane motion or a different source of motion), the two-dimensional correlation-based measure used in nuSG is able to track the motion more accurately.
Nurse Adaptability and Post-traumatic Stress Disorder Symptoms During the COVID-19 Pandemic: The Effects of Family and Perceived Organizational Support
Authors: Cockerham Mona , Beier Margaret E. , Branson Sandy , Boss Lisa 
Published: March 2022

ObjectiveTo examine the effect of family and perceived organizational support on the relationship between nurse adaptability and their experience with COVID-related PTSD (post-traumatic stress disorder) symptoms in frontline nurses working on COVID-19 units.BackgroundProximity to and survival of life-threatening events contribute to a diagnosis of PTSD, which is characterized by avoidance of reminders of trauma, intrusive thoughts, flashbacks of events, sleep disturbances, and hypervigilance. Using the job-demands and resource model, we examined the effect of adaptability, family support, and perceived organizational support on PTSD symptoms for nurses during the COVID-19 pandemic. Specifically, we tested whether perceptions of environmental supports—i.e., family and organizational support—moderated the relationship between nurse adaptability and COVID-related PTSD symptoms.MethodsA sample of frontline nurses working on COVID-19 units during the COVID-19 pandemic in Texas (N= 277) participated in this cross-sectional, observational study. Frontline Nurses reported demographic information and completed surveys designed to measure adaptability, perceived organizational support, family support, and COVID-related PTSD symptoms.ResultsAdaptability was significantly positively correlated (medium effects) to perceived organizational and family support (r= 0.51 and 0.56, respectively,p&lt; 0.01). Adaptability and perceived organizational support were also negatively correlated with COVID-related PTSD symptoms (medium effects). Adaptability was negatively correlated with COVID-related PTSD symptoms, supporting Hypothesis 1 (r= −0.43,p&lt; 0.01). Perceived organizational support was also significantly negatively correlated with COVID-19-related PTSD symptoms (r= −0.30,p&lt; 0.01). Family support was not significantly correlated with COVID-related PTSD but was positively related to experiencing COVID-related PTSD after other variables were accounted for.ConclusionFindings suggest that individual adaptability and organizational support may reduce PTSD severity in frontline nurses working during a crisis; however, family support may increase PTSD symptoms. We provide suggestions for strengthening individual adaptability and healthcare leadership including remaining highly engaged to show support by providing rapid communication, remaining calm during difficult circumstances, and maintaining a consistent, physical presence during difficult times. Moreover, our results suggest additional support for nurses with families to adapt to crisis.
Improving the Emotional Distress and the Experience of Hospitalization in Children and Adolescent Patients Through Animal Assisted Interventions: A Systematic Review
Authors: Correale Cinzia , Borgi Marta , Collacchi Barbara , Falamesca Chiara , Gentile Simonetta , Vigevano Federico , Cappelletti Simona , Cirulli Francesca 
Published: March 2022

IntroductionAnimal Assisted Interventions (AAIs) are increasingly common in pediatric care settings as a means to promote the physical, mental, and emotional well-being of hospitalized children and adolescents.ObjectivesThe aim of this work was to review published studies implementing AAIs in hospital settings and to assess the effects of AAIs on the biobehavioral response to stress and pain, social behavior, quality of life and level of satisfaction with hospitalization in children and adolescents. Stress and burden, quality of life, mood and level of satisfaction with hospitalization in parents/caregivers as well as stress and burden, perception of the work environment and job satisfaction in hospital staff were also reviewed.MethodsAll published studies reporting quantitative assessments were systematically searched using PubMed, Scopus, ProQuest and Web of Science databases in accordance with PRISMA guidelines. The aim was to identify studies examining the effects of AAIs on behavioral, psychological and physiological responses to stress in children and adolescents (0–18 years) formally admitted to a hospital for a stay, as well as in those undergoing a visit for treatments or medical examinations.ResultsOf the 350 studies screened, 21 were eligible for inclusion. Most of them focused on stress, pain, and anxiety reduction in pediatric patients, and used both physiological parameters and behavioral and psychological observations/scales. All studies employed dogs. Results show the potential of AAIs to reduce anxiety and behavioral distress in pediatric patients while acting on physiological measures associated with arousal.ConclusionAlthough further, more rigorous studies are still needed, the findings of this review may have implications for clinical practices suggesting appropriate planning of AAIs by pediatric healthcare professionals.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=178993], identifier [CRD42020178993].
Social Support and Spiritual Well-Being of Patients With Esophageal Cancer Aged Over 50 Years: The Mediating Role of Rumination
Authors: Li Jingran , Xue Liang , Pan Hailong 
Published: March 2022

BackgroundSpiritual well-being plays an important role in helping patients cope with disease. Previous studies have investigated the association between social support and spiritual well-being, whereas few studies have explored the relationship in patients with esophageal cancer (EC), and the mechanisms behind this pathway have not been thoroughly examined.ObjectiveThis study aimed to explore the relationship between social support and spiritual well-being of Chinese patients with EC aged over 50 years and to analyze whether the relationship was mediated by rumination.MethodsA cross-sectional survey was conducted with 197 EC patients. Participants completed the general information questionnaire, the Functional Assessment of Chronic Illness Therapy–Spiritual Scale, the Chinese Event Related Rumination Inventory, and the Perceived Social Support Scale (PSSS).ResultsResults demonstrated that social support of patients with EC aged over 50 years was positively correlated with spiritual well-being and deliberate rumination and negatively correlated with intrusive rumination; spiritual well-being was positively associated with deliberate rumination and negatively correlated with intrusive rumination. The effect of social support on spiritual well-being was partially mediated by deliberate rumination and intrusive rumination.ConclusionsThe findings suggest that interventions directed toward enhancing social support and deliberate rumination and reducing the level of intrusive rumination may help patients with EC aged over 50 years improve spiritual well-being.
Which Contributes to Clinical Performance: Academic Output or Person–Environment Fit?
Authors: Dong Minye , Xiao Yuyin , Shi Chenshu , Zeng Wu , Wu Fan , Li Guohong 
Published: March 2022

BackgroundThe measures put in place by health authorities to ensure the professionalism of doctors are important. Hospitals in China have included academic outputs in the promotion criteria to incentive medical clinicians to engage in scientific research so that to improve job performance (JP). However, such practice disproportionally focuses on academic outputs but ignores the force of needs fulfilled brought by intrinsic incentive. This study aims to discuss the realistic problem regarding the promotion mechanism and the potential drivers to clinical JP.MethodsThis study was based on multi-source data collection on clinical performance from electric medical record (EMR), person-environment (P–E) fit from the survey, and academic output from personnel files of ward clinicians (n = 244) of general public hospitals who sought for career progression in Shanghai in 2020. Independent-Sample t-test and chi-square test were used for comparison of two sample means or constituent ratio between promoted and not promoted clinicians. Linear multilevel regression was conducted to examine the relationship between clinical performance and academic outputs and P–E fit.ResultsClinicians who were promoted were more productive in producing academic outputs than those who were not (t = −5.075, p &lt; 0.001). However, there was no difference in clinical performance between the two groups (t = −1.728 to 0.167, p &gt; 0.05). The regression showed that academic outputs were not related to clinical performance, while higher P–E fit was associated with the improvement of various clinical performances.ConclusionThis study shows that P–E fit plays a more important role in facilitating clinical performance than academic performance and highlights the importance of intrinsic motivation of clinicians in achieving clinical performance.
The Role of Psychological Capital and Work Engagement in Enhancing Construction Workers' Safety Behavior
Authors: Saleem Muhammad Shoaib , Isha Ahmad Shahrul Nizam , Yusop Yuzana Mohd , Awan Maheen Iqbal , Naji Gehad Mohammed Ahmed 
Published: March 2022

ObjectivesConstruction is one of the unsafe industrial sectors, causing a considerable amount of harm to its workforce and organizations globally. Only a handful of research evidence has been found evaluating individuals' cognitive and engagement-related constructs to improve occupational safety. Psychological Capital (PsyCap) can have a promising impact on construction workers' psychological health, possibly leading to positive performance. Limited studies have tested PsyCap and work engagement regarding safety specifically in the context of the construction industry, with non-harmonious findings.MethodsThe proposed framework was assessed through the structural equation modeling (SEM) technique along with bootstrapping for mediation analysis. Responses were collected from different states of Malaysia from 345 construction workers. PsyCap dimensions (hope, efficacy, resilience, and optimism) were measured in connection with safety compliance and safety participation, with the mediating role of work engagement.ResultsAccording to findings, hope, optimism, and work engagement have a positive and significant impact on safety compliance. Also, hope, self-efficacy, resilience, optimism, and work engagement have a positive and significant impact on safety participation. Further, self-efficacy and optimism both have a positive impact on work engagement.ConclusionsPsyCap can be a possible predictor for work engagement, which may enhance safety-related behavior. PsyCap should be treated as a multidimensional instrument to enhance occupational safety. In-depth deliberation is needed by the organization while applying PsyCap to enhance employees' work engagement as well as safety behavior. Practical interventions based on interactive training are proposed to enhance construction industry safety. Other industries can also adapt suitable dimension(s) of PsyCap to safety behavior improvements.
Balancing Outcome vs. Urgency in Modern Liver Transplantation
Authors: Dancs Peter T. , Saner Fuat H. , Benkö Tamas , Molmenti Ernesto P. , Büchter Matthias , Paul Andreas , Hoyer Dieter P. 
Published: March 2022

BackgroundCurrent allocation mechanisms for liver transplantation (LT) overemphasize emergency, leading to poorer longtime outcomes. The utility was introduced to recognized outcomes in allocation. Recently, Molinari proposed a predictive outcome model based on recipient data.AimsThe aims of this study were to validate this model and to combine it with the utility to emphasize outcome in allocation.MethodsWe retrospectively analyzed 734 patients who were transplanted between January 2010 and December 2019. Points were assigned as in Molinari's model and the score sum was correlated with observed 90-day mortality. The utility was calculated as the product of 1-year survival times 3-month mortality on the waiting list. The weighting of different compounds was introduced, and utility curves were calculated. Model for End-Stage Liver Disease (MELD) scores according to maximal utility were determined.ResultsIn total, 120 patients (16.3%) had died within 90 days after LT. Higher MELD score, obesity, and hemodialysis prior to LT were confirmed risk factors. Overall survival was 83.8 and 77.4% after 90 days and 12 months, respectively. General utility culminated at MELD scores &gt;35 in the overall population. Emphasizing the outcome shifted the maximal utility to lower MELD scores depending on Molinari scores.ConclusionsEmphasizing outcome, at least in certain recipient risk categories, might improve the longtime outcomes and might be integrated into allocation models.