bluuebunny/crossref_metadata_2025 huggingface dataset:
How Does Enlistment Motivation Shape Organizational Commitment? The Role of Career Identity and Organizational Support
Authors: Zhou Jie , Zhang Jianwei , Hua Weijun , Zhao Mingming
Published: June 2022

This study, based on the integrative model of commitment and motivation and organizational support theory, examined the mechanism of intrinsic and extrinsic enlistment motivation on three facets of organizational commitment. A three-wave field questionnaire survey was conducted among 1606 Reserve Officers’ Training Corps cadets from Chinese universities. The results showed that both intrinsic and extrinsic motivation positively predicted affective commitment, normative commitment, and continuous commitment. The positive effect of intrinsic motivation was stronger than extrinsic motivation. However, the interactive effect of intrinsic and extrinsic motivation negatively predicted the three aspects of organizational commitment. Career identity mediated all the direct effects above. Moreover, organizational support moderated the effects of intrinsic and extrinsic motivation on career identity. When organizational support was low, the positive effect of intrinsic motivation on career identity was stronger; whereas, when organizational support was high, the positive effect of extrinsic motivation on career identity was stronger. Furthermore, extrinsic motivation and organizational support jointly moderated the effect of intrinsic motivation on career identity and the mediating effects between intrinsic motivation and the three facets of organizational commitment. Specifically, when extrinsic motivation and organizational support were low, the direct and mediating effects above were stronger.
Parenting in a Pandemic: Preliminary Support for Delivering Brief Behavioral Parent Training Through Telehealth
Authors: Holzman Jacob B. W. , Hawks Jessica L. , Kennedy Sarah M. , Anthony Bruno J. , Anthony Laura G.
Published: June 2022

Behavioral problems, such as noncompliance and aggression, are a common referral reason to mental health services for young children. Behavioral parent training (BPT) is the leading intervention for addressing behavioral problems and leads to benefits in a variety of parental factors (e.g., parenting efficacy and parenting stress). While the COVID-19 pandemic dramatically shifted service delivery toward telehealth services, limited work has evaluated the effectiveness of BPT when delivered in a brief, group format through telehealth. The current retrospective chart review study evaluated the engagement to and preliminary effectiveness of a brief version of BPT delivered through telehealth to 64 families of 3- to 7-year-olds referred for behavioral problems. Families attended an average of 4.55 of 6 sessions and most families had two caregivers who engaged in the intervention. Significant reductions in caregivers’ report of children’s behavioral problems and improvements in parenting self-efficacy resulted. Future research and clinical implications are discussed.
Can the Arts Cure Pandemic Hearts? - Cultural Activity During the COVID-19 Pandemic and its Consequences for Psychological Well-Being
Authors: Gotthardt Karina Aylin , Rakoczy Katrin , Tallon Miles , Seitz Matthias , Frick Ulrich
Published: June 2022

Cultural activities might serve as a buffer to the negative effects of the COVID-19 pandemic on mental health. Frequencies of participants’ cultural activities in terms of participation in digital cultural offerings or self-initiated cultural activities during the pandemic are examined, and whether prior cultural engagement and valuing of culture have an impact on this participation. It is explored whether both forms of cultural activities are directly connected with psychological well-being, namely, optimism concerning COVID-19, and whether this relationship is mediated by autonomy, relatedness and aesthetic experience. Regression and mediation analysis were calculated (N = 398). Both cultural activities were related to increased aesthetic experience and perceived autonomy, but only participation in digital cultural offerings was connected to increased perceived relatedness. Relatedness, in turn, was connected to increased optimism. The results reflect the protective function of cultural activities on psychological well-being, demonstrating the importance of cultural life in times of adversity.
A review of the tribological properties of nanoparticles dispersed in bio-lubricants
Authors: Abd Elhaseeb Diaa M , Ali Mohamed Kamal Ahmed , Ezzat MF , Mourad M.
Published: June 2022

Mineral oil resources are dwindling and the mineral-based lubricants are not compatible with the environment, and thus there is great interest in replacing them with bio-based lubricants. Automotive engines are an important application for bio-lubricants. In this context, this review investigates recent advances and research gaps in automotive-related applications of bio-based lubricants. The main objective of the current article is to review the tribological and thermophysical properties of nanoparticles in bio-oils, which could be used as a reference in the future development of bio-lubricants. The various nanomaterials, concentrations, surfactants, and mixing techniques have been presented. The key mechanisms which can result in superior tribological and thermal behavior of bio-lubricants are explained. Studies on the tribo-chemical reactions and between nano-additives and bio-oils are included in this review. It was reported that the tribological and thermophysical performance of bio-oils could be improved especially after adding nanomaterials according to the recent studies results. Furthermore, the major challenges for developing bio-lubricants performance are illustrated. Our present review assists in providing a basis to select bio-oils, nano-additives, and chemical processing according to their tribological properties.
Genome-wide alternative splicing profile in the posterior kidney of brown trout (Salmo trutta) during proliferative kidney disease
Authors: Sudhagar Arun , El-Matbouli Mansour , Kumar Gokhlesh
Published: June 2022

Background

The cnidarian myxozoan parasite Tetracapsuloides bryosalmonae causes chronic proliferative kidney disease (PKD) in salmonids. This parasite is a serious threat to wild and cultured salmonids. T. bryosalmonae undergoes intra-luminal sporogonic development in the kidney of brown trout (Salmo trutta) and the viable spores are released via urine. We investigated the alternative splicing pattern in the posterior kidney of brown trout during PKD.

Results

RNA-seq data were generated from the posterior kidney of brown trout collected at 12 weeks post-exposure to T. bryosalmonae. Subsequently, this data was mapped to the brown trout genome. About 153 significant differently expressed alternatively spliced (DEAS) genes, (delta PSI = 5%, FDR P-value < 0.05) were identified from 19,722 alternatively spliced events. Among the DEAS genes, the least and most abundant alternative splicing types were alternative 5′ splice site (5.23%) and exon skipping (70.59%), respectively. The DEAS genes were significantly enriched for sodium-potassium transporter activity and ion homeostasis (ahcyl1, atp1a3a, atp1a1a.1, and atp1a1a.5). The protein-protein interaction network analysis enriched two local network clusters namely cation transporting ATPase C-terminus and Sodium/potassium ATPase beta chain cluster, and mixed inclusion of Ion homeostasis and EF-hand domain cluster. Furthermore, the human disease-related salmonella infection pathway was significantly enriched in the protein-protein interaction network.

Conclusion

This study provides the first baseline information about alternative splicing in brown trout during PKD. The generated data lay a foundation for further functional molecular studies in PKD - brown trout infection model. The information generated from the present study can help to develop therapeutic strategies for PKD in the future.
Comparative genomic analysis revealed genetic divergence between Bifidobacterium catenulatum subspecies present in infant versus adult guts
Authors: Liu Jiaqi , Li Weicheng , Yao Caiqing , Yu Jie , Zhang Heping
Published: June 2022

Background

The two subspecies of Bifidobacterium catenulatum, B. catenulatum subsp. kashiwanohense and B. catenulatum subsp. catenulatum, are usually from the infant and adult gut, respectively. However, the genomic analysis of their functional difference and genetic divergence has been rare. Here, 16 B. catenulatum strains, including 2 newly sequenced strains, were analysed through comparative genomics.

Results

A phylogenetic tree based on 785 core genes indicated that the two subspecies of B. catenulatum were significantly separated. The comparison of genomic characteristics revealed that the two subspecies had significantly different genomic sizes (p < 0.05) but similar GC contents. The functional comparison revealed the most significant difference in genes of carbohydrate utilisation. Carbohydrate-active enzymes (CAZyme) present two clustering patterns in B. catenulatum. The B. catenulatum subsp. kashiwanohense specially including the glycoside hydrolases 95 (GH95) and carbohydrate-binding modules 51 (CBM51) families involved in the metabolism of human milk oligosaccharides (HMO) common in infants, also, the corresponding fucosylated HMO gene clusters were detected. Meanwhile, B. catenulatum subsp. catenulatum rich in GH3 may metabolise more plant-derived glycan in the adult intestine.

Conclusions

These findings provide genomic evidence of carbohydrate utilisation bias, which may be a key cause of the genetic divergence of two B. catenulatum subspecies.
Genome-wide association mapping and genomic prediction for pre‑harvest sprouting resistance, low α-amylase and seed color in Iranian bread wheat
Authors: Rabieyan Ehsan , Bihamta Mohammad Reza , Moghaddam Mohsen Esmaeilzadeh , Mohammadi Valiollah , Alipour Hadi
Published: June 2022

Background

Pre-harvest sprouting (PHS) refers to a phenomenon, in which the physiologically mature seeds are germinated on the spike before or during the harvesting practice owing to high humidity or prolonged period of rainfall. Pre-harvest sprouting (PHS) remarkably decreases seed quality and yield in wheat; hence it is imperative to uncover genomic regions responsible for PHS tolerance to be used in wheat breeding. A genome-wide association study (GWAS) was carried out using 298 bread wheat landraces and varieties from Iran to dissect the genomic regions of PHS tolerance in a well-irrigated environment. Three different approaches (RRBLUP, GBLUP and BRR) were followed to estimate prediction accuracies in wheat genomic selection.

Results

Genomes B, A, and D harbored the largest number of significant marker pairs (MPs) in both landraces (427,017, 328,006, 92,702 MPs) and varieties (370,359, 266,708, 63,924 MPs), respectively. However, the LD levels were found the opposite, i.e., genomes D, A, and B have the highest LD, respectively. Association mapping by using GLM and MLM models resulted in 572 and 598 marker-trait associations (MTAs) for imputed SNPs (− log10 P > 3), respectively. Gene ontology exhibited that the pleitropic MPs located on 1A control seed color, α-Amy activity, and PHS. RRBLUP model indicated genetic effects better than GBLUP and BRR, offering a favorable tool for wheat genomic selection.

Conclusions

Gene ontology exhibited that the pleitropic MPs located on 1A can control seed color, α-Amy activity, and PHS. The verified markers in the current work can provide an opportunity to clone the underlying QTLs/genes, fine mapping, and genome-assisted selection.Our observations uncovered key MTAs related to seed color, α-Amy activity, and PHS that can be exploited in the genome-mediated development of novel varieties in wheat.
Management practice and treatment outcomes of adult patients with Lupus Nephritis at the Renal Clinic of St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia
Authors: Hailu Gebre-Mariam Tsegay , Hussen Shemsu Umer , Getachew Seifemichael , Berha Alemseged Beyene
Published: June 2022

Background

Lupus nephritis (LN) is the most common severe complication of systemic lupus erythematosus (SLE) which results in high morbidity and mortality. Up to 60% of adult patients with SLE develop the renal disease with different severity. Even with potent anti-inflammatory and immunosuppressive therapies, many LN patients still progress to chronic kidney disease or end-stage renal disease. Thus, this study aimed to assess the management practice, treatment outcomes and to identify the associated factors of poor renal outcome in adult LN patients at the renal clinic of St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia.

Methods

A retrospective cross-sectional study design was used to collect the data using an abstraction tool from patients’ records. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to diagnose LN among SLE patients. Logistic regression was used to determine crude and adjusted odds ratio and a p-value of < 0.05 was considered statistically significant. Ethical approval was obtained from the ethical review committee of the School of Pharmacy, Addis Ababa University and institutional review board of St. Paul’s Hospital Millennium Medical College.

Results

Out of 168 study participants enrolled from September 1, 2016 to October 30, 2020, a total of 114 adult LN patients were included for final analysis. The mean (± SD) age of the LN patients at onset was 29.10 ± 9.67 years and 99 (86.8%) of all the patients were females. More than three-fourths (78.9%) of the LN patients had a good prognosis. However, 24 (21.1%) of the patients who didn’t achieve complete or partial remission had a poor prognosis. A kidney biopsy was done for 71 patients at initial presentation with class IV and III as the commonest class. The commonly prescribed immunosuppressive medications were cyclophosphamide as induction therapy in 67 (58.7%) and mycophenolate mofetil (MMF) as maintenance therapy in 76 (66.7%). Gastrointestinal intolerances like abdominal pain, nausea, or diarrhea from MMF were the most common 27(31.2%) treatment-related adverse events reported. Acute kidney injury (AKI) at onset (AOR = 4.83, P = 0.026), high serum creatinine (SCr) at six months (AOR = 0.12, P = 0.003), no response at six months to attain complete remission (AOR = 0.05, P = 0.041) and presence of flare (AOR = 0.04, P = 0.004) were predictors poor treatment outcomes.

Conclusion

Despite good response with the present immunosuppressive regimens, relapse, treatment-related complications and adverse events are major problems that require close monitoring. The results and identified gaps of this study are used as an input to improve the management practice of LN in the study setting. Overall, this study is comparable with other findings and strengthen the present available literatures.
Intratumoral fibrosis and patterns of immune infiltration in clear cell renal cell carcinoma
Authors: Han Songchen , Yang Wenbo , Qin Caipeng , Du Yiqing , Ding Mengting , Yin Huaqi , Xu Tao
Published: June 2022

Background

Intratumoral fibrosis was positively correlated with histological grade of renal clear cell carcinoma (ccRCC) and intratumoral inflammation. However, the association of intratumoral fibrosis with the immune infiltration of ccRCC was few evaluated.

Methods

We used the second harmonic generation (SHG)-based imaging technology and evaluated the intratumoral fibrosis in ccRCC, and then divided the patients into the high fibrosis group (HF) and the low fibrosis group (LF). Meanwhile, the Kaplan–Meier survival curve analysis was performed to analyze the relationship between intratumoral fibrosis and the disease-free survival rate. Antibody arrays were used for seeking difference in cytokines and immune infiltration between the HF group (N = 11) and LF group (N = 11). The selected immune infiltration marker was then verified by immunohistochemistry (IHC) staining in 45 ccRCC samples.

Results

Out of 640 cytokines and immune infiltration markers, we identified 115 proteins that were significantly different in quantity between ccRCC and adjacent normal tissues. In addition, the Venn diagram indicated that six proteins, including Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), were significantly associated with intratumoral fibrosis (p < 0.05). The GO/KEGG enrichment analysis indicated that the proteins associated with intratumoral fibrosis were involved in the immunity and tumor-infiltrating lymphocytes. The expression of the CTLA4 was negatively correlated with collagen level, confirmed by IHC staining of CTLA4 (p < 0.05).

Conclusions

The study indicated that the intratumoral fibrosis level was negatively correlated with the expression of CTLA4 in the tumor immune microenvironment of the ccRCC, which posed the potential value of targeting the stroma of the tumor, a supplement to immunotherapy. However, the specific mechanism of this association is still unclear and needs further investigation.
Circulating tumour cell gene expression and chemosensitivity analyses: predictive accuracy for response to multidisciplinary treatment of patients with unresectable refractory recurrent rectal cancer or unresectable refractory colorectal cancer liver metastases
Authors: Guadagni Stefano , Masedu Francesco , Fiorentini Giammaria , Sarti Donatella , Fiorentini Caterina , Guadagni Veronica , Apostolou Panagiotis , Papasotiriou Ioannis , Parsonidis Panagiotis , Valenti Marco , Ricevuto Enrico , Bruera Gemma , Farina Antonietta R. , Mackay Andrew R. , Clementi Marco
Published: June 2022

Background

Patients with unresectable recurrent rectal cancer (RRC) or colorectal cancer (CRC) with liver metastases, refractory to at least two lines of traditional systemic therapy, may receive third line intraarterial chemotherapy (IC) and targeted therapy (TT) using drugs selected by chemosensitivity and tumor gene expression analyses of liquid biopsy-derived circulating tumor cells (CTCs).

Methods

In this retrospective study, 36 patients with refractory unresectable RRC or refractory unresectable CRC liver metastases were submitted for IC and TT with agents selected by precision oncotherapy chemosensitivity assays performed on liquid biopsy-derived CTCs, transiently cultured in vitro, and by tumor gene expression in the same CTC population, as a ratio to tumor gene expression in peripheral mononuclear blood cells (PMBCs) from the same individual. The endpoint was to evaluate the predictive accuracy of a specific liquid biopsy precision oncotherapy CTC purification and in vitro culture methodology for a positive RECIST 1.1 response to the therapy selected.

Results

Our analyses resulted in evaluations of 94.12% (95% CI 0.71–0.99) for sensitivity, 5.26% (95% CI 0.01–0.26) for specificity, a predictive value of 47.06% (95% CI 0.29–0.65) for a positive response, a predictive value of 50% (95% CI 0.01–0.98) for a negative response, with an overall calculated predictive accuracy of 47.22% (95% CI 0.30–0.64).

Conclusions

This is the first reported estimation of predictive accuracy derived from combining chemosensitivity and tumor gene expression analyses on liquid biopsy-derived CTCs, transiently cultured in vitro which, despite limitations, represents a baseline and benchmark which we envisage will be improve upon by methodological and technological advances and future clinical trials.
Spatial analysis of vaccine coverage on the first year of life in the northeast of Brazil
Authors: Cunha Nairmara Soares Pimentel , Fahrat Sylvia Costa Lima , de Olinda Ricardo Alves , Braga Alfésio Luís Ferreira , Barbieri Carolina Luisa Alves , de Aguiar Pontes Pamplona Ysabely , Martins Lourdes Conceição
Published: June 2022

Background

Over time, vaccination has been consolidated as one of the most cost effective and successful public health interventions and a right of every human being. This study aimed to assess the spatial dynamics of the vaccine coverage (VC) rate of children aged < 1 year per municipality in the Brazilian Northeast at 2016 and 2017.

Methods

This is a mixed-type ecological study that use a Public domain data Health Information. Vaccine doses were obtained from the Information System of the Brazilian National Immunization Program, and live births from the Brazilian Information System of Live Births of the Brazilian Unified Health System. Descriptive analysis of the coverage of all the vaccines for each year of the study was conducted, and Mann–Whitney U test was used to compare VC between the study years. Chi-squared test was used to evaluate the association between the years and VC, which was stratified into four ranges, very low, low, adequate, and high. Spatial distribution was analyzed according to both each study year and vaccine and presented as thematic maps. Spatial autocorrelation was analyzed using Moran’s Global and Local statistics.

Results

Compared with 2017, 2016 showed better VC (p < 0.05), except for Bacillus Calmette–Guérin. In the spatial analysis of the studied vaccines, the Global Moran’s Index did not show any spatial autocorrelation (p > 0.05), but the Local Moran’s Index showed some municipalities, particularly the Sertão Paraibano region, with high VC, high similarity, and a positive influence on neighboring municipalities (p < 0.05). In contrast, most municipalities with low VC were concentrated in the Mata Paraibano region, negatively influencing their neighbors (p < 0.05).

Conclusion

Uneven geographic regions and clusters of low VC for children aged < 1 year in the State of Paraíba were spatially visualized. Health policy makers and planners need to urgently devise and coordinate an action plan directed at each state’s regions to fulfill the vaccination calendar, thereby reversing the vulnerability of this age group, which is at a higher risk of diseases preventable by vaccination.
Effect of alendronate sodium plus vitamin D3 tablets on knee joint structure and osteoarthritis pain: a multi-center, randomized, double-blind, placebo-controlled study protocol
Authors: Peng Hui-ming , Weng Xi-sheng , Li Ye , Feng Bin , Qian Wenwei , Cai Dao-zhang , Zhao Chang , Yao Zhen-jun , Yang Yi , Zhang Chi , Wan Shengcheng
Published: June 2022

Background

Osteoarthritis (OA) is a major cause of pain and disability worldwide. Despite the relatively high burden of the disease, the currently available non-surgical treatment options are directed towards symptomatic relief. Therefore, we propose the use of alendronate as a disease modifying agent to help slow and prevent OA. In addition, this study will utilize Whole-Organ Magnetic Resonance Imaging Score (WORMS) to evaluate the structural integrity of cartilage in the study population. High-quality evidence, limited to a few well-conducted randomized trials, highlights contradictory results on the effect of bisphosphonates on knee function and progression of OA. Therefore, a placebo-controlled, randomized trial is needed to evaluate the combined effect of alendronate and vit D on the structure of cartilage utilizing the WORMS score and its ability to treat knee pain in OA patients.

Methods

This multicenter, randomized, double-blinded, placebo-controlled study will evaluate the efficacy and safety of alendronate in early OA. Patients will undergo a 1:1 double-blinded randomization to receive a one-year course of either alendronate sodium vitamin D3 or placebo. The primary outcome is to compare WORMS score of knee joint at 6 and 12 months between both groups. Secondary endpoints will include WORMS score at 24 months, knee pain, radiographic progression of OA, severity of OA, quality of life, and serum inflammatory biomarkers at different assessment timepoints. To detect a 2.2% difference in cartilage loss between both groups with power of 80%, a sample size of 60 (30 per group) is proposed.

Discussion

This trial will give helpful and high-quality evidence regarding the potential therapeutic role of alendronate sodium vitamin D3, as compared to placebo, in the management of patients with knee OA regarding its role on cartilage loss, radiographic progression of OA, severity of OA, knee pain, quality of life, and inflammatory biomarkers. If proven effective, this intervention would be a great option for providing beneficial outcomes with a reduced cost in this patient population.

Trial registration

This trial was registered on clinicaltrials.gov (registration number: NCT04739592).
Hidden blood loss of total knee arthroplasty in hemophilia arthritis: an analysis of influencing factors
Authors: Shen Shao Ning , Wu Dong Xiao , Lv Shuai Jie , Tong Pei Jian
Published: June 2022

Background

Total knee arthroplasty is the leading way to treat hemophilia arthritis. At present, there is a lack of research on the influencing factors of blood loss in total knee arthroplasty for hemophilia arthritis. This study comprehensively explores the definite factors affecting the hidden blood loss in total knee arthroplasty for hemophilia patients.

Materials and methods

Ninety-two hemophilia A patients who underwent total knee arthroplasty in our center were included. Demographics, laboratory data, surgical data, and complications were collected. The Gross equation and Sehat equation were used to calculate the estimated value of hidden blood loss. Multivariate linear regression analysis was used to determine the influencing factors of hidden blood loss.

Result

The hidden blood loss of hemophilia A patients undergoing total knee arthroplasty was 1069.51 ± 341.99 mL, and the age was positively correlated with the hidden blood loss (P < 0.001), while tranexamic acid, FVIII prophylaxis, and incremental invivo recovery were negatively correlated with the hidden blood loss (P < 0.001, P = 0.008, P = 0.017).

Conclusion

Elderly patients have a greater risk of blood loss, and additional preventive measures can be appropriately added. Intraoperative intra-articular injection of tranexamic acid is recommended to reduce hidden blood loss, FVIII prophylaxis is recommended for every patient. We recommend that all HA patients measure the incremental invivo recovery and develop a personalized infusion regimen of coagulation factor.
Hypoxia-inducible factor expression is related to apoptosis and cartilage degradation in temporomandibular joint osteoarthritis
Authors: Zhang Jun , Hu Yu , Wang Zihan , Wu Xuelian , Yang Chun , Yang Hefeng
Published: June 2022

Background

It remains unclear etiology of cartilaginous tissues in osteoarthritis (OA) lesions. In this study, we hypothesized the accumulation of hypoxia-inducible factor (HIF) and activated apoptosis relate to condylar cartilage degeneration in vivo.

Methods

Malocclusion stress was applied for 2 weeks, 4 weeks and 8 weeks to induce an OA-like lesion animal model in rats. Histological analysis was performed by H&E staining and Safranin O/fast green staining. The expression levels of protein in condylar cartilage were examined by immunostaining to evaluate cartilage degeneration.

Results

We found apparent histological phenotypes associated with degeneration in the occlusion disorder (OD) stress group. The OD group at 4 weeks and 8 weeks had obviously reduced expression of Aggrecan (Acan) and type II collagen (Col II) in cartilage. In contrast, the OD groups had higher levels of ADAM metallopeptidase with thrombospondin type 5 (ADAMTS5) and matrix metallopeptidase 13 (MMP13) in the condylar cartilage than the control group. Moreover, the OD group cartilage had prominent degenerative changes with reduced levels of hypoxia inducible factor 1 alpha (HIF1α) and increased levels of hypoxia inducible factor 2 alpha (HIF2α) and the apoptosis factor Caspase3 in condylar cartilage at 8 weeks.

Conclusion

Thus, abnormal hypoxic conditions inducing Occlusion disorder stress results in cartilage degeneration. opposite expression patterns of HIF1α and HIF2α could be involved in the pathogenesis of condylar cartilage degeneration and chondrocyte apoptosis. HIF2α may provide a potential negative feedback mechanism for HIF1α during cartilage damage.
Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX
Authors: Trabelsi Khaled , Zakour Meriem Ben , Jordan Ingo , Sandig Volker , Rourou Samia , Kallel Hela
Published: June 2022

Background

Mass vaccination of dogs as important rabies reservoir is proposed to most effectively reduce and eliminate rabies also in humans. However, a minimum coverage of 70% needs to be achieved for control of the disease in zoonotic regions. In numerous developing countries, dog vaccination rate is still dangerously low because of economic constraints and due to a high turnover in dog populations. Improved vaccine production processes may help to alleviate cost and supply limitations. In this work, we studied and optimized the replication and vaccine potency of PV rabies virus strain in the muscovy-duck derived AGE1.CR and AGE1.CR.pIX suspension cell lines.

Results

The BHK-21-adapted PV rabies virus strain replicated efficiently in the avian cell lines without requirement for prior passaging. CR.pIX was previously shown to augment heat shock responses and supported slightly higher infectious titers compared to the parental CR cell line. Both cell lines allowed replication of rabies virus also in absence of recombinant IGF, the only complex component of the chemically defined medium that was developed for the two cell lines. After scale-up from optimization experiments in shake flask to production in 7-l bioreactors peak virus titers of 2.4 × 108 FFU/ml were obtained. The potency of inactivated rabies virus harvest according to the NIH test was 3.5 IU/ml. Perfusion with the chemically defined medium during the virus replication phase improved the potency of the vaccine twofold, and increased the number of doses 9.6 fold.

Conclusion

This study demonstrates that a rabies vaccine for animal vaccination can be produced efficiently in the AGE1.CR.pIX suspension cell line in a scalable process in chemically defined medium.
Falsely elevated serum estradiol in woman of reproductive age led to unnecessary intervention and delayed fertility opportunity: a case report and literature review
Authors: Zhang Jing , Xu Liangzhi , Qiao Lin
Published: June 2022

Background

The optimal management of patients in reproductive endocrinology relies on the accuracy and validity of sex hormone assays. Endogenous or exogenous substances can compete with the analyte. This competition can result in interfering errors and falsely indicate elevated serum levels. Obvious interference in estradiol assays appears to occur rarely. Consequently, clinicians who are not familiar with the potential of interference could be misled. In addition to unnecessary investigations and interventions and severe mental stress, falsely elevated estradiol results can result in missed or delayed fertility opportunities.

Case

A 28-year-old female with pregnancy demand was diagnosed with polycystic ovary syndrome, Hashimoto’s thyroiditis and subclinical hypothyroidism. She was found to have persistently elevated levels of serum estradiol in the early follicular phase (between 527 and 642 pg/mL). Screening workup was performed for nearly 11 months to find the causes. Serum tumor biomarkers were normal. Abdominal and pelvic computed tomography were negative for adrenal or adnexal masses. A left mesosalpinx cyst and benign pathological results were achieved by laparoscopic surgery. Hormonal substances and dietary supplements were absent, as determined by dietary records. Ultrasound confirmed follicles could grow slowly and eventually ovulate. Falsely elevated estradiol levels were suspected due to the discrepancy among high estradiol levels, follicle growth and normal gonadotropin levels. Immunological interference by heterophile antibody was finally verified by two competitive chemiluminescent immunoassay platforms (estradiol levels in the early follicle phase: 619 pg/mL, Siemens ADVIA CENTAUR and 60 pg/mL, Beckman, DxI 800). Successful clinical pregnancy was eventually achieved by combining induced ovulation, ultrasound monitoring and intercourse guidance.

Conclusions

Analytical interference and laboratory error should be suspicious at first when the clinical characteristics contradict the laboratory results of serum hormones. Measuring serum estradiol with another immunoassay platform is an easy and non-time-consuming method to exclude the heterophile interfering.
A team approach to delivery of contextually relevant bioscience: encouraging student connections between tacit knowledge and new content acquisition
Authors: Reynolds Mikaela , Bowers Cristina , Peters Holly , Klein Mathilde , Clayton Zane , Hagger David , McGarry Ben , Pelzer Elise
Published: June 2022

Background

Bioscience is essential knowledge for nursing practice and is an important component of undergraduate nursing education, however students commonly feel anxious about studying the subject. The purpose of this study was to develop appropriately scoped contextually relevant bioscience lesson resources to enhance student engagement and performance and reduce attrition and unit failures over a sustained period.

Methods

Participants included students enrolled in the core bioscience unit for an undergraduate Bachelor of Nursing degree from a central campus and a widening participation (WP) campus. From 2016 to 2018, unit learning resources were progressively revised to include a structured learning and teaching manual, signposted lectures, and digital resources. Online surveys and formal institutional data collection metrics were used to assess the impact of the changes to unit learning resources.

Results

Student attrition rates and failure rates for the unit were reduced over a two-year period across a diverse student cohort.

Conclusions

Scaffolded and diverse learning materials support the success of undergraduate bioscience students by improving student engagement and reducing cognitive load.
Reliability and validity of the Persian version of the ACE tool: assessing medical trainees’ competency in evidence-based medicine
Authors: Habibi Mohammad Amin , Amini Mitra , Ostovarfar Maral , Ostovarfar Jeyran , Moosavi Mahsa , Keshavarzi Mohammad Hasan
Published: June 2022

Background

Evidence-based medicine (EBM) allows users to integrate evidence into decision-making alongside clinical expertise and patient values. This study aimed to evaluate the reliability and validity of the Persian version of the Assessing Competency in EBM (ACE) tool across knowledge, skills, and attitude.

Methods

This cross-sectional study was performed on medical residents (first-year residents and junior residents) of Shiraz University of Medical Sciences in 2019. The study instrument was the ACE tool which consists of 15 two-choice questions (yes–no) and each of these questions measures one of four steps in evidence-based medicine (1- asking the answerable question, 2- searching the literature, 3- critical appraisal, and 4- applying the evidence to scenario). This tool was translated into Persian according to international standards. To ensure that the original and translated ACE questionnaire can be matched accurately and conceptuality, content validity index (CVI) and content validity ratio (CVR) were determined. Cronbach’s alpha was applied to determine the internal consistency for each scale and Confirmatory factor analysis (CFA) was used to survey the factor structure validity.

Results

One hundred sixty-three questionnaires were studied, selecting 59 first-year medical residents and 104 s-year medical residents. The results showed that using the Persian translation of the ACE tools, the content validity index (CVI) values were equal to or above 0.8 for all items. The content validity ratio (CVR) value was 0.90 for the total scale. The indicators of the confirmatory factor analysis (CFA) for the ACE tool revealed that this model had an acceptable fit. Cronbach’s alpha for the overall score was 0.79.

Conclusion

The Persian translated version of the ACE tool is a valid and reliable instrument for assessing medical trainees’ competency in EBM.
A Delphi study to explore clinician and lived experience perspectives on setting priorities in eating disorder services
Authors: Richards Katie L. , Woolrych Isabel , Allen Karina L. , Schmidt Ulrike
Published: June 2022

Background

Due to scarce resources and high demand, priority setting in mental health services is necessary and inevitable. To date, no study has examined priority setting in eating disorder (ED) services specifically. Here, we evaluate the level of consensus and perceived relative importance of factors used to determine patient prioritisation in ED services, amongst clinicians and individuals with lived experience (LE) of an ED.

Methods

A three round Delphi study and a ranking task were used to determine the level of consensus and importance. Consensus was defined as > 80% agreement or disagreement. Items that reached consensus for agreement were ranked in order of importance from most to least important. Participants were 50 ED clinicians and 60 LE individuals. Participant retention across rounds 2, 3, and 4 were 92%, 85%, and 79%, respectively.

Results

Over three iterative rounds, a total of 87 statements about patient prioritisation were rated on a 5-point Likert-scale of agreement. Twenty-three items reached consensus in the clinician panel and 20 items reached consensus in the LE panel. The pattern of responding was broadly similar across the panels. The three most important items in both panels were medical risk, overall severity, and physical health deteriorating quickly. Clinicians tended to place greater emphasis on physical risk and early intervention whereas the LE panel focused more on mental health and quality of life.

Conclusions

Eating disorder services tend to prioritise patients based upon medical risk and severity, and then by the order in which patients are referred. Our findings align in some respects with what is observed in services, but diverge in others (e.g., prioritising on quality of life), providing important novel insights into clinician and LE opinions on waiting list prioritisation in EDs. More research is warranted to validate these findings using multi-criterion decision techniques and observational methods. We hope these findings provide a foundation for future research and encourage evidence-based conversations around priority setting in ED services.
Effects of glycemic traits on left ventricular structure and function: a mendelian randomization study
Authors: Ai Sizhi , Wang Xiaoyu , Wang Shanshan , Zhao Yilin , Guo Shuxun , Li Guohua , Chen Zhigang , Lin Fei , Guo Sheng , Li Yan , Zhang Jihui , Zhao Guoan
Published: June 2022

Background

Adverse ventricular structure and function is a key pathogenic mechanism of heart failure. Observational studies have shown that both insulin resistance (IR) and glycemic level are associated with adverse ventricular structure and function. However, whether IR and glycemic level are causally associated with cardiac structure and function remains unclear.

Methods

Genetic variants for IR, fasting insulin, HbA1c, and fasting glucose were selected based on published genome-wide association studies, which included 188,577, 108,557, 123,665, and 133,010 individuals of European ancestry, respectively. Outcome datasets for left ventricular (LV) parameters were obtained from UK Biobank Cardiovascular Magnetic Resonance sub-study (n = 16,923). Mendelian randomization (MR) analyses with the inverse-variance weighted (IVW) method were used for the primary analyses, while weighted median, MR-Egger, and MR-PRESSO were used for sensitivity analyses. Multivariable MR analyses were also conducted to examine the independent effects of glycemic traits on LV parameters.

Results

In the primary IVW MR analyses, per 1-standard deviation (SD) higher IR was significantly associated with lower LV end-diastolic volume (β = − 0.31 ml, 95% confidence interval [CI] − 0.48 to − 0.14 ml; P = 4.20 × 10−4), lower LV end-systolic volume (β = − 0.34 ml, 95% CI − 0.51 to − 0.16 ml; P = 1.43 × 10−4), and higher LV mass to end-diastolic volume ratio (β = 0.50 g/ml, 95% CI 0.32 to 0.67 g/ml; P = 6.24 × 10−8) after Bonferroni adjustment. However, no associations of HbA1c and fasting glucose were observed with any LV parameters. Results from sensitivity analyses were consistent with the main findings, but with a slightly attenuated estimate. Multivariable MR analyses provided further evidence for an independent effect of IR on the adverse changes in LV parameters after controlling for HbA1c.

Conclusions

Our study suggests that genetic liability to IR rather than those of glycemic levels are associated with adverse changes in LV structure and function, which may strengthen our understanding of IR as a risk factor for heart failure by providing evidence of direct impact on cardiac morphology.
Restoration of Cullin3 gene expression enhances the improved effects of sonic hedgehog signaling activation for hypertension and attenuates the dysfunction of vascular smooth muscle cells
Authors: Shen Jian , Li Youqi , Li Menghao , Li Zhiming , Deng Huantang , Xie Xiongwei , Liu Jinguang
Published: June 2022

Background

Hypertension is known as a major factor for global mortality. We aimed to investigate the role of Cullin3 (CUL3) in the regulation of hypertension.

Material and methods

Human vascular smooth muscle cells (VSMCs) were treated with Angiotensin II (Ang II) to establish a hypertension in vitro model. Cell viability was detected by a cell counting kit-8 (CCK-8) assay. The content of reactive oxygen species (ROS) was evaluated by kit. Transwell assay and TUNEL staining were, respectively, used to assess cell migration and apoptosis. Additionally, the expression of sonic hedgehog (SHH) signaling-related proteins (SHH, smoothened homolog (Smo) and glioblastoma (Gli)) and CUL3 was tested with western blotting. Following treatment with Cyclopamine (Cycl), an inhibitor of SHH signaling, in Ang II-induced VSMCs, cell viability, migration, apoptosis and ROS content were determined again. Then, VSMCs were transfected with CUL3 plasmid or/and treated with sonic hedgehog signaling agonist (SAG) to explore the impacts on Ang II-induced VSMCs damage. In vivo, a hypertensive mouse model was established. Systolic blood pressure and diastolic blood pressure were determined. The histopathologic changes of abdominal aortic tissues were examined using H&E staining. The expression of SHH, Smo, Gli and CUL3 was tested with western blotting.

Results

Significantly increased proliferation, migration and apoptosis of VSMCs were observed after Ang II exposure. Moreover, Ang II induced upregulated SHH, Smo and Gli expression, whereas limited increase in CUL3 expression was observed. The content of ROS in Ang II-stimulated VSMCs presented the same results. Following Cycl treatment, the high levels of proliferation and migration in Ang II-treated VSMCs were notably remedied while the apoptosis and ROS concentration were further increased. Moreover, Cycl downregulated SHH, Smo, Gli and CUL3 expression. Above-mentioned changes caused by Ang II were reversed following SAG addition. Indeed, SAG treatment combined with restoration of CUL3 expression inhibited proliferation, migration, apoptosis and ROS level in Ang II-stimulated VSMCs. In vivo, SAG aggravated the histopathological changes of the aorta and with a worse tendency after both SAG intervention and CUL3 silencing. By contrast, SAG treatment and rebound in CUL3 expression alleviated the vascular damage.

Conclusions

Collectively, restoration of CUL3 gene expression protected against hypertension through enhancing the effects of SHH activation in inhibition of apoptosis and oxidative stress for hypertension and alleviating the dysfunction of VSMCs.
Gestational weight gain during the second and third trimesters and adverse pregnancy outcomes, results from a prospective pregnancy cohort in urban Tanzania
Authors: Yang Jiaxi , Wang Molin , Tobias Deirdre K. , Rich-Edwards Janet W. , Darling Anne Marie , Abioye Ajibola I. , Pembe Andrea B. , Madzorera Isabel , Fawzi Wafaie W.
Published: June 2022

Background

Appropriate gestational weight gain (GWG) is important for optimal pregnancy outcomes. This study prospectively evaluated the associations between GWG during the second and third trimesters of pregnancy and adverse pregnancy outcomes in an urban Tanzanian pregnancy cohort.

Methods

We used data from a randomized clinical trial conducted among pregnant women recruited by 27 weeks of gestation in Dar es Salaam, Tanzania (N = 1230). Women’s gestational weight was measured at baseline and at monthly antenatal visits. Weekly GWG rate during the second and third trimesters was calculated and characterized as inadequate, adequate, or excessive, in conjunction with measured or imputed early-pregnancy BMI status according to the 2009 Institute of Medicine (IOM) GWG guidelines. We used multivariable Poisson regression with a sandwich variance estimator to calculate risk ratios (RR) for associations of GWG with low birth weight, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). Degree of appropriate GWG defined using additional metrics (i.e., percentage of adequacy, z-score) and potential effect modification by maternal BMI were additionally evaluated.

Results

According to the IOM guidelines, 517 (42.0%), 270 (22.0%), and 443 (36.0%) women were characterized as having inadequate, adequate, and excessive GWG, respectively. Overall, compared to women with adequate GWG, women with inadequate GWG had a lower risk of LGA births (RR = 0.54, 95% CI: 0.36–0.80) and a higher risk of SGA births (RR = 1.32, 95% CI: 0.95–1.81). Women with inadequate GWG as defined by percentage of GWG adequacy had a higher risk of LBW (OR = 1.93, 95% CI: 1.03–3.63). In stratified analyses by early-pregnancy BMI, excessive GWG among women with normal BMI was associated with a higher risk of preterm birth (RR = 1.59, 95% CI: 1.03–2.44).

Conclusions

A comparatively high percentage of excessive GWG was observed among healthy pregnant women in Tanzania. Both inadequate and excessive GWGs were associated with elevated risks of poor pregnancy outcomes. Future studies among diverse SSA populations are warranted to confirm our findings, and clinical recommendations on optimal GWG should be developed to promote healthy GWG in SSA settings.

Trial registration:This trial was registered as “Prenatal Iron Supplements: Safety and Efficacy in Tanzania” (NCT01119612;http://clinicaltrials.gov/show/NCT01119612).