bluuebunny/crossref_metadata_2025 huggingface dataset:
Interweaving Arts-Based, Qualitative and Mixed Methods Research: Showcasing Integration and Knowledge Translation Through Material and Narrative Reflection
Authors: Archibald Mandy M
Published: May 2022

Arts-based research can exist as a stand-alone method, methodology, or reflect varying degrees of interweaving with other research approaches. With this in mind, this paper explores these relationships using examples from a recent arts-based research exhibition inclusive of various artistic works created to respond to, understand, and reflect nuanced experiences, narratives, contradictions, and diverse data sources in frailty and aging research. Taking an interdisciplinary perspective positioned between the arts and health sciences with specific attention to knowledge translation, the roles of object materiality, proximity to research data, and narrative reflection are considered, as are their implications for the creation and purpose of arts-based research more generally. The paper encourages researchers to consider how research data and arts-based research can continue to evolve and create deeply impactful and resonating findings.
Accuracy of head computed tomography scoring systems in predicting outcomes for patients with moderate to severe traumatic brain injury: A ProTECT III ancillary study
Authors: Wu Haijun , Wright David W , Allen Jason W , Ding Victoria , Boothroyd Derek , Glushakova Olena Y , Hayes Ron , Jiang Bin , Wintermark Max
Published: May 2022

Background

Several types of head CT classification systems have been developed to prognosticate and stratify TBI patients.

Objective

The purpose of our study was to compare the predictive value and accuracy of the different CT scoring systems, including the Marshall, Rotterdam, Stockholm, Helsinki, and NIRIS systems, to inform specific patient management actions, using the ProTECT III population of patients with moderate to severe acute traumatic brain injury (TBI).

Methods

We used the data collected in the patients with moderate to severe (GCS score of 4–12) TBI enrolled in the ProTECT III clinical trial. ProTECT III was a NIH-funded, prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial designed to determine the efficacy of early administration of IV progesterone. The CT scoring systems listed above were applied to the baseline CT scans obtained in the trial. We assessed the predictive accuracy of these scoring systems with respect to Glasgow Outcome Scale—Extended at 6 months, disability rating scale score, and mortality.

Results

A total of 882 subjects were enrolled in ProTECT III. Worse scores for each head CT scoring systems were highly correlated with unfavorable outcome, disability outcome, and mortality. The NIRIS classification was more strongly correlated than the Stockholm and Rotterdam CT scores, followed by the Helsinki and Marshall CT classification. The highest correlation was observed between NIRIS and mortality (estimated odds ratios of 4.83).

Conclusion

All scores were highly associated with 6-month unfavorable, disability and mortality outcomes. NIRIS was also accurate in predicting TBI patients’ management and disposition.
Induced pluripotent stem cell-based organ-on-a-chip as personalized drug screening tools: A focus on neurodegenerative disorders
Authors: Fanizza Francesca , Campanile Marzia , Forloni Gianluigi , Giordano Carmen , Albani Diego
Published: May 2022

The Organ-on-a-Chip (OoC) technology shows great potential to revolutionize the drugs development pipeline by mimicking the physiological environment and functions of human organs. The translational value of OoC is further enhanced when combined with patient-specific induced pluripotent stem cells (iPSCs) to develop more realistic disease models, paving the way for the development of a new generation of patient-on-a-chip devices. iPSCs differentiation capacity leads to invaluable improvements in personalized medicine. Moreover, the connection of single-OoC into multi-OoC or body-on-a-chip allows to investigate drug pharmacodynamic and pharmacokinetics through the study of multi-organs cross-talks. The need of a breakthrough thanks to this technology is particularly relevant within the field of neurodegenerative diseases, where the number of patients is increasing and the successful rate in drug discovery is worryingly low. In this review we discuss current iPSC-based OoC as drug screening models and their implication in development of new therapies for neurodegenerative disorders.
Peri-Articular Injection of Tranexamic Acid Reduce Blood Loss and Transfusion Requirement During Total Knee Arthroplasty: A Meta-analysis
Authors: Liu Yue , Shan Duo , Tian Peng , Li Zhi-jun , Xu Gui-jun , Fu Xin
Published: May 2022

Background

The aim of this meta-analysis was to evaluate the efficacy and safety of peri-articular injection of tranexamic acid (TXA) during total knee arthroplasty (TKA) from clinical controlled trials.

Method

Eligible scientific articles published prior to October 2021 were retrieved from the PubMed, Springer, ScienceDirect and Cochrane Library databases. The statistical analysis was performed with RevMan 5.1.

Result

2 RCTs and 3 non-RCTs met the inclusion criteria. Meta-analysis showed significant differences in terms of hemoglobin reduction (MD = −1.04, 95% CI: −1.33 to −.76, P < .00001), total blood loss (MD = −342.80.70, 95% CI: −437.52 to −248.08, P < .00001), drainage volume (MD = −297.24, 95% CI: −497.26 to −97.23, P = .004) and blood transfusion rate (OR = .30, 95% CI: .14 to .62, P = .001) were found in the control group. No postoperative infection and deep venous thrombosis were found between 2 groups.

Conclusion

Peri-articular injection of TXA can effectively decrease perioperative blood loss and blood transfusion rate without increasing the incidence of postoperative complications during TKA.
Relationship between Principal Leadership Style and Student Achievement: A Comparative Study between Germany and China
Authors: Chen Dan , Ning Bo , Bos Wilfried
Published: May 2022

This article explored the different clusters of leadership styles and the relationship between principal leadership style and student academic achievement in domains of mathematics, reading, science, and collaborative problem-solving in Germany and China. We used PISA 2015 data covering 6,504 students and 256 school principals from German schools and 9,841 students and 268 school leaders from Chinese schools. Results identified three leadership styles in Germany, namely, transformational (23.4%), instructional (41.3%), and integrated (35.3%) leadership, and two leadership styles in China, namely, transformational (38.6%) and instructional (61.4%) principals. Principals with instructional and integrated leadership had higher student achievements in Germany, whereas only principals with transformational leadership had slightly higher student achievements in China. Moreover, three leadership styles in Germany and two in China showed their relationships with each domain of student achievement. In conclusion, principals in Germany and China had different priorities in leading schools. The differences that principal leadership made on student achievements highlighted the differences in principals’ situational context and leading characteristics between Germany and China.
Ligament Augmentation Reconstruction System (LARS) for Ankle Lateral Ligament Reconstruction in Higher-Risk Patients: A 5-Year Prospective Cohort Study
Authors: Porter Mark D. , Trajkovska Aleksandra , Georgousopoulou Ekavi
Published: May 2022

Background:

The modified Broström-Gould (MBG) procedure is the gold standard for patients with chronic ankle instability (CAI), but it is relatively contraindicated for patients with higher body weight or generalized ligamentous laxity (GLL). The use of the ligament augmentation reconstruction system (LARS) is an alternative.

Hypothesis:

It was hypothesized that clinical outcomes would be similar in patients with increased body weight (>90 kg) or GLL, relative to controls.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

A total of 66 patients satisfying the inclusion criteria were invited to participate and were divided into 3 groups: controls (no risk factors for inferior clinical outcome), patients with body weight >90 kg, and patients with GLL (Beighton score, ≥5 of 9). All patients underwent imbrication of the lateral collateral ligament complex augmented with the LARS. Primary outcomes of interest were Tegner activity scale (TAS) and Foot and Ankle Outcome Score (FAOS) subscale scores. Secondary outcomes were recurrence of ankle instability, the need for further surgery, and/or complications. Patients were reviewed at 2 and 5 years postoperatively, and outcomes between groups were compared using repeated-measures analysis of variance.

Results:

Complete data were available for 63 patients (21 patients in each group). TAS improved in all groups from preoperatively to 2 years and 5 years postoperatively ( P < .001 for all). Relative to the controls, the TAS scores were lower in the >90-kg group at 2 years and 5 years ( P < .001 for both periods), while the GLL group had similar scores to controls at both postoperative periods. Both the >90-kg and the GLL groups showed no significant difference in improvement on any FAOS subscale scores relative to the controls, at both 2 and 5 years postoperatively. There were no recurrences, repeat surgeries, or major complications.

Conclusion:

Relative to controls, patients with body weight >90 kg or GLL had similar FAOSs, and TAS scores were lower in the >90-kg group, at 2 and 5 years, after the use of the LARS to augment lateral collateral ligament imbrication for CAI. Use of the LARS in this manner is a viable option in patients for whom the MBG procedure is relatively contraindicated.
Development of a planning support system to evaluate transit-oriented development masterplan concepts for optimal health outcomes
Authors: Hooper Paula , Bolleter Julian , Edwards Nicole
Published: May 2022

There is growing consensus that planning professionals need clearer guidance on features of the built environment that promote health benefits. Concomitantly, the smart city movement has created renewed opportunity and interest in data-driven urban modelling to support land use planning. Planning Support Systems (PSS) are spatially enabled computer-based analytical tools incorporating health-related metrics that apply empirical evidence on built environment relationships with health-related outcomes to inform real-world urban design, urban planning and transportation planning decisions. This paper presents the development of the Urban Health Check PSS to use local empirical data to explore and predict relative health impacts associated with proposed urban design planning changes from alternative new station precinct masterplan concepts. We present a case study where we compare a baseline scenario with alternative design concepts for a new train station precinct in Perth, Western Australia, that incorporated possible built environment interventions. Subsequently, we discuss potential future applications of health impact PSS for the translation and application of health evidence into practice.
Ability of municipality-level deprivation indices to capture social inequalities in perinatal health in France: A nationwide study using preterm birth and small for gestational age to illustrate their relevance
Authors: Barry Yaya , Le Strat Yann , Azria Elie , Gorza Maud , Pilkington Hugo , Vandentorren Sthéphanie , Gallay Anne , Regnault Nolwenn
Published: May 2022

Background

Evidence-based policy-making to reduce perinatal health inequalities requires an accurate measure of social disparities. We aimed to evaluate the relevance of two municipality-level deprivation indices (DIs), the French-Deprivation-Index (FDep) and the French-European-Deprivation-Index (FEDI) in perinatal health through two key perinatal outcomes: preterm birth (PTB) and small-for-gestational-age (SGA).

Methods

We used two data sources: The French National Perinatal Surveys (NPS) and the French national health data system (SNDS). Using the former, we compared the gradients of the associations between individual socioeconomic characteristics (educational level and income) and “PTB and SGA” and associations between municipality-level DIs (Q1:least deprived; Q5:most deprived) and “PTB and SGA”. Using the SNDS, we then studied the association between each component of the two DIs (census data, 2015) and “PTB and SGA”. Adjusted odds ratios (aOR) were estimated using multilevel logistic regression with random intercept at the municipality level.

Results

In the NPS (N = 26,238), PTB and SGA were associated with two individual socioeconomic characteristics: maternal educational level (≤ lower secondary school vs. ≥ Bachelor’s degree or equivalent, PTB: aOR = 1.43 [1.22–1.68], SGA: (1.31 [1.61–1.49]) and household income (< 1000 € vs. ≥ 3000 €, PTB: 1.55 [1.25–1.92], SGA: 1.69 [1.45–1.98]). For both FDep and FEDI, PTB and SGA were more frequent in deprived municipalities (Q5: 7.8% vs. Q1: 6.3% and 9.0% vs. 5.9% for PTB, respectively, and 12.0% vs. 10.3% and 11.9% vs. 10.2% for SGA, respectively). However, after adjustment, neither FDep nor FEDI showed a significant gradient with PTB or SGA. In the SNDS (N = 726,497), no FDep component, and only three FEDI components were significantly associated (specifically, the % of the population with ≤ lower secondary level of education with both outcomes (PTB: 1.5 [1.15–1.96]); SGA: 1.25 [1.03–1.51]), the % of overcrowded (i.e., > 1 person per room) houses (1.63 [1.15–2.32]) with PTB only, and unskilled farm workers with SGA only (1.52 [1.29–1.79]).

Conclusion

Some components of FDep and FEDI were less relevant than others for capturing ecological inequalities in PTB and SGA. Results varied for each DI and perinatal outcome studied. These findings highlight the importance of testing DI relevance prior to examining perinatal health inequalities, and suggest the need to develop DIs that are suitable for pregnant women.
Anatomy of intergovernmental finance for essential public health services in China
Authors: Tan Xiao , Wong Christine
Published: May 2022

Background

The Chinese government launched health care reforms in 2009 and introduced a national list of essential public health services (EPHS) as an integral part of the plan to deliver health care for all. EPHS was also built into the national plan to promote the equalisation of public services across the country. A national standard was set for financial input to EPHS. As the services are co-funded by the central and local governments, a robust intergovernmental fiscal system is essential to guarantee that the hundreds of thousands of service providers have adequate financing to meet the service commitment.

Methods

We examined the flow of funds through China’s complex intergovernmental fiscal system to see whether the promise of equal funding for EPHS was implemented, and how the costs were distributed across levels of government. Information was collated from funding documents issued by all levels of governments involved, for a sample that includes the central government, 12 provincial governments, eight prefectural governments and 11 county-level governments. For each level of government, we examined: (i) when and how much funding they disbursed or received from higher levels; (ii) when and how much matching funds were made; and (iii) the allocation rules adopted.

Results

Overall, we found the central government met its commitments for the program on time and in full, and good compliance from local governments in passing through funding from higher levels and as well as meeting their own financial responsibilities. However, we also found the following problems: (i) the involvement of so many levels of government resulted in delays in the disbursement of funds; (ii) the use of outdated population data in calculating required funding resulted in some under-allocation; and (iii) localities that needed funding the most were not well targeted by the distribution of funds.

Conclusion

This study traces how the 2018 subsidy for EPHS was disbursed from the central government to service providers, focusing on the roles played by intermediate levels of subnational governments—provinces, prefectures and counties. In this way, it identifies gaps in the current intergovernmental financing of EPHS and points to areas for further improvement.
Features of alcohol advertisements across five urban slums in Kampala, Uganda: pilot testing a container-based approach
Authors: Swahn Monica H. , Palmier Jane B. , May Alicia , Dai Dajun , Braunstein Sarah , Kasirye Rogers
Published: May 2022

Background

Despite the high prevalence of alcohol use and marketing in many settings across sub-Saharan Africa, few studies have systematically sought to assess alcohol marketing exposure, particularly in vulnerable areas such as urban slums where alcohol is often highly prevalent but where educational programs and alcohol prevention messages are scarce.

Objective

To pilot test the development and implementation of environmental scans of alcohol advertisements in five urban slums across different areas of Kampala, Uganda: Bwaise, Kamwokya, Makindye, Nakulabye, and Nateete.

Methods

Each of the five scans was conducted in geographical circles, within a 500-m radius of a Uganda Youth Development Link (UYDEL) drop-in Center using a container-based approach. Using a Garmin GPS with photo capabilities and a tablet for data entry, teams of at least two trained researchers walked the main roads within the target area and gathered information about each alcohol advertisement including its location, type, size, and placement and other characteristics. Data with the GPS coordinates, photos and descriptive details of the adverts were merged for analyses.

Results

A total of 235 alcohol adverts were found across all five data collection sites reflecting 32 different brands. The majority of the adverts (85.8%) were smaller and medium sizes placed by restaurants and bars, stores and kiosks, and liquor stores. The most frequently noted types of alcohol in the adverts were spirits (50.6%) and beer (30.6%).

Recommendations

The pilot test of the methodology we developed indicated that implementation was feasible, although challenges were noted. Since monitoring alcohol marketing is key for addressing underage alcohol use and harm, the advantages and disadvantages of the approach we developed are discussed. Future research needs to strengthen and simplify strategies for monitoring alcohol marketing in low-resource settings such as urban slums which have unique features that need to be considered. Meanwhile, the findings may yield valuable information for stakeholders and to guide intervention developments and alcohol marketing policy to protect youth.
Blood pressure control status of patients with hypertension on treatment in Dessie City Northeast Ethiopia
Authors: Fentaw Zinabu , Adamu Kidist , Wedajo Shambel
Published: May 2022

Introduction

Uncontrolled blood pressure contributes a huge contribution to many hypertension-related complications and it is one of the unbeaten problems for patients taking antihypertensive drugs. The association of social support and other factors with uncontrolled blood pressure during the covid-19 pandemic is not well investigated. Therefore, this study explored the determinants of blood pressure control status during the COVID-19 pandemic among patients with hypertension who were on an antihypertensive treatment.

Method

A cross-sectional study was done from March to May 2021 among adults aged 18 or more patients with hypertension for three months or more on treatment in Dessie City. An interview-administered questionnaire was done using simple random sampling from hypertension follow-up register for 380 patients with hypertension. Blood pressure measurement was taken from their arm using a stethoscope and mercury sphygmomanometer at a sitting position with 90-degree back support. Uncontrolled blood pressure was also computed either the systolic or diastolic blood pressure greater than or less than the limit of uncontrolled blood pressure with regarding the age and diabetic status of patients. The perceived social support-related questionnaire was adopted from the Multidimensional Scale of Perceived Social Support (MSPSS) -12 item checklist. It was sum-up and transformed into three categories using tertile of their computed raw scores. The adjusted prevalence ratio with a 95 percent confidence interval (CI) was used to calculate the strength of the association between uncontrolled blood pressure and independent predictors using log-binomial regression analysis. A P-value less than 0.05 was declared as statistically significant in multivariable log-binomial regression analysis.

Result

A total of 360 study participants were included in this study. The prevalence of uncontrolled blood measures in patients with hypertension with a 95% CI was 55.8(50.7, 61.0). In a multivariable analysis adjusted prevalence ratio with 95% CI for poor medication adherence 1.86(1.59,2.19), being male 1.35(1.11,1.64), secondary education 0.52(0.35,0.77), and low social support 1.24(1.01, 1.54) were the predictors of uncontrolled blood pressure.

Conclusion

Uncontrolled blood pressure for patients with hypertension on treatment is higher during the COVID-19 pandemic. Being male, poor medication adherence, educational status and low social support are factors that contribute to uncontrolled blood pressure.
Working intentions of medical students in response to healthcare workplace violence and descending resources reform in China
Authors: Wang Shuhong , Zhao Hongjun , Sun Zesheng
Published: May 2022

Background

In order to curb healthcare workplace violence (WPV) and better allocate healthcare resources, China launched the descending resources reform in 2013 and tightened the anti-violence legal environment simultaneously. Medical students are expected to reconsider their working intentions of entering the medical market (inter-market effect) and choosing high- or low-level hospitals (intra-market effect) in response to the evolving WPV. The goal of this study was to explore the link between the perceived WPV incidence and medical students’ willingness to practice medicine in the context of China’s descending resources reform.

Method

Medical students were selected with cluster sampling from 8 medical colleges in Zhejiang Province, China, and 1497 valid questionnaires were collected by using a five-point unbalanced scale, to perform cross-sectional empirical research using the ordered logit model (OLM).

Results

The perceived WPV incidence negatively correlate with the willingness of medical students to practice medicine but positively correlate with their willingness to practice in low-level hospitals, indicating the existence of inter- and intra-market effects. The anti-violence legal environment has no direct link with working intention but contributes to the perceived decline in the incidence of violence. Descending resources reform has simultaneous opposite effects on medical students, with the coexistence of prudent motives driven by reform costs and optimistic expectations of sharing external benefits.

Conclusions

Safety needs and risk aversion motive play an important role in medical students’ career choice when facing severe WPV. Tightening of the anti-violence legal environment and the descending resources reform could drive medical students to low-level hospitals.
The effect of a mobile-learning curriculum on improving compliance to quality management guidelines for HIV rapid testing services in rural primary healthcare clinics, KwaZulu-Natal, South Africa: a quasi-experimental study
Authors: Chamane Nkosinothando , Ebenezer Ogunsakin Ropo , Mashamba-Thompson Tivani Phosa
Published: May 2022

Background

Despite significant achievements made towards HIV testing, linkage to antiretroviral therapy treatment and viral load suppression, the Sub-Saharan region of Africa continues to be reported to have the highest prevalence of HIV/AIDS, with over 26 million people living with the disease. In light of the added burden on already overwhelmed health systems due to the Covid-19 pandemic, maintaining the reliability and accuracy of point-of-care diagnostics (POC) results is crucial to ensure the sustainability of quality service delivery. The integration of technology-based interventions into nurse education curricula is growing, to help prepare students for the current practice environment which requires access to large amounts of information. The aim of this study was to determine the effect of a Mobile Learning (mLearning) Curriculum on improving the quality of HIV rapid testing services in rural clinics of KwaZulu-Natal (KZN), South Africa.

Methods

To achieve the aim of this study, pre-test and post-test audits were conducted in a quasi-experimental design. Eleven clinics of KZN, with the highest availability and usage of POC diagnostics were selected from a cross-sectional study survey to constitute the sample of this study. The World Health Organization On-site Monitoring Checklist-Assessment of Quality System was adapted and used as an audit tool to evaluate four key quality components. The effect of the mLearning curriculum on HIV testing quality improvement was determined through statistically comparing pre-audit and post-audit results. The independent samples t-test and the Levene’s test were employed to evaluate the equality of measured variables for the two groups. The relationships between variables were estimated using the Pearson pair wise correlation coefficient (p) and correlations were reported as significant at p < 0.05.

Results

A total of 11 clinics was audited at the pretest and 7 clinics were audited post-piloting of the mLearning curriculum. The estimated level of compliance of the participating clinics to quality HIV rapid testing guidelines ranged between poor and moderate quality. The mLearning curriculum was shown to have no statistically significant effect on the quality of POC diagnostic services provided in rural clinics of KZN.

Conclusion

The mLearning curriculum was shown to have no statistically significant effect on the quality of HIV rapid testing services provided in participating clinics; however, multiple barriers to the full adoption of the piloted curriculum were identified. The provision of reliable technology devices and improved internet connection were recommended to enhance the adoption of technology-based interventions necessary to improve access to relevant learning material and updated information.
Natural product myricetin is a pan-KDM4 inhibitor which with poly lactic-co-glycolic acid formulation effectively targets castration-resistant prostate cancer
Authors: Liu Jai-Shin , Fang Wei-Kai , Yang Shan-Min , Wu Meng-Chen , Chen Tsan-Jan , Chen Chih-Ming , Lin Tung-Yueh , Liu Kai-Lun , Wu Chien-Ming , Chen Yun-Ching , Chuu Chih-Pin , Wang Ling-Yu , Hsieh Hsing-Pang , Kung Hsing-Jien , Wang Wen-Ching
Published: May 2022

Background

Castration-resistant prostate cancer (CRPC) with sustained androgen receptor (AR) signaling remains a critical clinical challenge, despite androgen depletion therapy. The Jumonji C-containing histone lysine demethylase family 4 (KDM4) members, KDM4A‒KDM4C, serve as critical coactivators of AR to promote tumor growth in prostate cancer and are candidate therapeutic targets to overcome AR mutations/alterations-mediated resistance in CRPC.

Methods

In this study, using a structure-based approach, we identified a natural product, myricetin, able to block the demethylation of histone 3 lysine 9 trimethylation by KDM4 members and evaluated its effects on CRPC. A structure-based screening was employed to search for a natural product that inhibited KDM4B. Inhibition kinetics of myricetin was determined. The cytotoxic effect of myricetin on various prostate cancer cells was evaluated. The combined effect of myricetin with enzalutamide, a second-generation AR inhibitor toward C4-2B, a CRPC cell line, was assessed. To improve bioavailability, myricetin encapsulated by poly lactic-co-glycolic acid (PLGA), the US food and drug administration (FDA)-approved material as drug carriers, was synthesized and its antitumor activity alone or with enzalutamide was evaluated using in vivo C4-2B xenografts.

Results

Myricetin was identified as a potent α-ketoglutarate-type inhibitor that blocks the demethylation activity by KDM4s and significantly reduced the proliferation of both androgen-dependent (LNCaP) and androgen-independent CRPC (CWR22Rv1 and C4-2B). A synergistic cytotoxic effect toward C4-2B was detected for the combination of myricetin and enzalutamide. PLGA-myricetin, enzalutamide, and the combined treatment showed significantly greater antitumor activity than that of the control group in the C4-2B xenograft model. Tumor growth was significantly lower for the combination treatment than for enzalutamide or myricetin treatment alone.

Conclusions

These results suggest that myricetin is a pan-KDM4 inhibitor and exhibited potent cell cytotoxicity toward CRPC cells. Importantly, the combination of PLGA-encapsulated myricetin with enzalutamide is potentially effective for CRPC.
Combining nucleotide variations and structure variations for improving astaxanthin biosynthesis
Authors: Jin Jin , Jia Bin , Yuan Ying-Jin
Published: May 2022

Background

Mutational technology has been used to achieve genome-wide variations in laboratory and industrial microorganisms. Genetic polymorphisms of natural genome evolution include nucleotide variations and structural variations, which inspired us to suggest that both types of genotypic variations are potentially useful in improving the performance of chassis cells for industrial applications. However, highly efficient approaches that simultaneously generate structural and nucleotide variations are still lacking.

Results

The aim of this study was to develop a method of increasing biosynthesis of astaxanthin in yeast by Combining Nucleotide variations And Structure variations (CNAS), which were generated by combinations of Atmospheric and room temperature plasma (ARTP) and Synthetic Chromosome Recombination and Modification by LoxP-Mediated Evolution (SCRaMbLE) system. CNAS was applied to increase the biosynthesis of astaxanthin in yeast and resulted in improvements of 2.2- and 7.0-fold in the yield of astaxanthin. Furthermore, this method was shown to be able to generate structures (deletion, duplication, and inversion) as well as nucleotide variations (SNPs and InDels) simultaneously. Additionally, genetic analysis of the genotypic variations of an astaxanthin improved strain revealed that the deletion of YJR116W and the C2481G mutation of YOL084W enhanced yield of astaxanthin, suggesting a genotype-to-phenotype relationship.

Conclusions

This study demonstrated that the CNAS strategy could generate both structure variations and nucleotide variations, allowing the enhancement of astaxanthin yield by different genotypes in yeast. Overall, this study provided a valuable tool for generating genomic variation diversity that has desirable phenotypes as well as for knowing the relationship between genotypes and phenotypes in evolutionary processes.
Follicular fluid-derived exosomal miR-143-3p/miR-155-5p regulate follicular dysplasia by modulating glycolysis in granulosa cells in polycystic ovary syndrome
Authors: Cao Jianping , Huo Peng , Cui Kuiqing , Wei Huimei , Cao Junna , Wang Jinyuan , Liu Qingyou , Lei Xiaocan , Zhang Shun
Published: May 2022

Objective

Polycystic ovary syndrome (PCOS) is characterized by follicular dysplasia. An insufficient glycolysis-derived energy supply of granulosa cells (GCs) is an important cause of follicular dysplasia in PCOS. Follicular fluid (FF) exosomal microRNAs (miRNAs) have been proven to regulate the function of GCs. In this study, exosomes extracted from clinical FF samples were used for transcriptome sequencing (RNA-seq) analysis, and a human ovarian granulocyte tumour cell line (KGN cells) was used for in vitro mechanistic studies.

Methods and results

In FF exosomal RNA-seq analysis, a decrease in glycolysis-related pathways was identified as an important feature of the PCOS group, and the differentially expressed miR-143-3p and miR-155-5p may be regulatory factors of glycolysis. By determining the effects of miR-143-3p and miR-155-5p on hexokinase (HK) 2, pyruvate kinase muscle isozyme M2 (PKM2), lactate dehydrogenase A (LDHA), pyruvate, lactate and apoptosis in KGN cells, we found that upregulated miR-143-3p expression in exosomes from the PCOS group inhibited glycolysis in KGN cells; knockdown of miR-143-3p significantly alleviated the decrease in glycolysis in KGN cells in PCOS. MiR-155-5p silencing attenuated glycolytic activation in KGN cells; overexpression of miR-155-5p significantly promoted glycolysis in KGN cells in PCOS. In this study, HK2 was found to be the mediator of miR-143-3p and miR-155-5p in FF-derived exosome-mediated regulation of glycolysis in KGN cells. Reduced glycolysis accelerated apoptosis of KGN cells, which mediated follicular dysplasia through ATP, lactate and apoptotic pathways.

Conclusions

In conclusion, these results indicate that miR-143-3p and miR-155-5p in FF-derived exosomes antagonistically regulate glycolytic-mediated follicular dysplasia of GCs in PCOS.
Non-AUG translation initiation in mammals
Authors: Andreev Dmitry E. , Loughran Gary , Fedorova Alla D. , Mikhaylova Maria S. , Shatsky Ivan N. , Baranov Pavel V.
Published: May 2022

Recent proteogenomic studies revealed extensive translation outside of annotated protein coding regions, such as non-coding RNAs and untranslated regions of mRNAs. This non-canonical translation is largely due to start codon plurality within the same RNA. This plurality is often due to the failure of some scanning ribosomes to recognize potential start codons leading to initiation downstream—a process termed leaky scanning. Codons other than AUG (non-AUG) are particularly leaky due to their inefficiency. Here we discuss our current understanding of non-AUG initiation. We argue for a near-ubiquitous role of non-AUG initiation in shaping the dynamic composition of mammalian proteomes.
The efficacy and safety of Longmu Tang granule for the treatment of atopic dermatitis: study protocol for a single-centred, double-blinded, randomised, placebo-controlled trial
Authors: Li Ya-qin , Shen Tao-tao , Wang Qing-ying , Ma Meng-xi , Tian Feng-yan , She Yuan-yao , Tao Yi-cheng , Wang Jing-jing , Chi Hui-yan , Lang Na , Ren Jian-xun
Published: May 2022

Background

Atopic dermatitis (AD) is a chronic relapsing skin disease that has long-term physical and mental health impacts on children with this condition. Current treatments mainly include anti-inflammatory, antibacterial, and anti-allergic interventions, systemic therapy, and recently emerging target-focused agents. However, these treatments have limited effectiveness and unwanted side effects. The use of traditional Chinese medicine (TCM) in the treatment of AD has a long history, with promising efficacies, low toxicity, and improvements in the quality of life of patients with AD. Longmu Tang granule, a TCM, has been used to effectively treat AD since 2008 through doctors’ prescriptions. To scientifically evaluate the clinical efficacy and safety of Longmu Tang granule, we proposed to launch a single-centred, double-blinded, randomised, placebo-controlled trial.

Methods

In this single-centred, double-blinded, randomised, placebo-controlled clinical trial conducted at Xiyuan Hospital of China Academy of Chinese Medical Sciences, a total of 60 participants will be randomly assigned (1:1) to receive the Longmu Tang granule or placebo granule for 8 weeks. The primary outcome will be evaluated using the index of Scoring Atopic Dermatitis. The secondary outcomes will be evaluated using the Children’s Dermatology Life Quality Index and the number cancellation test. The mechanistic evidence will be the serum levels of inflammatory cytokines, including immunoglobulin E, tumour necrosis factor-α, interleukin-1, and interleukin-6.

Discussion

The results of this trial will provide evidence of the efficacy and safety of the Longmu Tang granule and prove its anti-inflammatory action in patients with AD.

Trial registration

Chinese Clinical Trial Registry Chictr.org ID: ChiCTR2100041591. Registered on 1 January 2021
Dipylidium caninum in the twenty-first century: epidemiological studies and reported cases in companion animals and humans
Authors: Rousseau Julieta , Castro Andry , Novo Teresa , Maia Carla
Published: May 2022

Background

Dipilidiosis is a parasitic disease caused by the tapeworm Dipylidium caninum. Fleas and, less frequently, lice act as an intermediate host, and their ingestion is required for infection to occur. While the disease mainly affects domestic and wild carnivores, it is also considered a zoonotic disease, with most human cases reported in children. Dipylidium caninum is considered to be the most common tapeworm infesting companion animals, but dipilidosis in humans is rare. The aims of this review were to improve current understanding of the epidemiology of this parasitosis and its management by the medical and veterinary community.

Methods

A comprehensive review of the published literature during the last 21 years (2000–2021) on the epidemiology, clinical features, diagnosis, treatment and prevention measures of D. caninum infection and dipilidiosis in companion animals and humans was conducted.

Results

Using predefined eligibility criteria for a search of the published literature, we retrieved and screened 280 publications. Of these, 161 (141 epidemiological studies, 20 case reports [16 human cases]) were considered for inclusion in this review. This parasitosis is present worldwide; however, despite being the most frequent cestode infection in animals, it is often underdiagnosed using common coprological techniques. Its diagnosis in humans has also proved challenging, being frequently confused with pinworm infection, leading to inappropriate treatment and to the persistence of the disease over time. Prevention measures include control of ectoparasites in animals and the environment, as well as regular deworming of animals, most commonly with praziquantel.

Conclusions

The diagnosis of dipilidiosis remains challenging in both animals and humans, primarily due to the low sensitivity of the diagnostic methods currently available and a lack of knowledge of the morphological characteristics of the parasite. Although treatment with the appropriate anti-cestode compounds is well tolerated and results in resolution of the infection, indiscriminate use of these compounds may predispose to an increase in resistance. Given the worldwide distribution of this parasite, it is essential to act on several fronts, with a focus on health education for children and animal owners and the control of intermediate hosts, both in animals and in the surrounding environment.

Graphical Abstract
Eight tips for the implementation of the first licenced peanut allergy oral immunotherapy into clinical practice
Authors: Portnoy Jay , Ciaccio Christina E. , Beausoleil Janet , Du Toit George , Fineman Stanley , Tilles Stephen A. , Zhang June , Lawrence Claire , Yassine Mohamed , Mustafa S Shahzad
Published: May 2022

Background

Shared learnings from the early use of novel therapies can aid in their optimization. The recent introduction of peanut oral immunotherapy (peanut OIT; Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp]) for peanut allergy addresses a significant unmet need but also highlights the requirement for consideration of several factors by both prescribers and patients.

Objective

To provide guidance for prescribers of licenced peanut OIT to facilitate treatment delivery and improve outcomes.

Methods

Clinicians with experience of licenced peanut OIT (United States n = 6, United Kingdom n = 1) participated in a series of interviews and group discussions designed to elicit tips for successful implementation.

Results

Clinicians identified 8 tips that were considered the most relevant, practical, and impactful for prescribers of Peanut (Arachis hypogaea) Allergen Powder-dnfp: (1) preparing to provide treatment, (2) assessing the medical indication for treatment and (3) shared decision making, (4) staff education, (5) establishing office processes, (6) managing patient expectations and using anticipatory guidance, (7) optimising adherence and (8) maintaining flexibility throughout the treatment process. In addition, a range of supporting materials (e.g., checklists and action plans) are provided.

Conclusion

The introduction of a novel therapy often requires healthcare providers to modify or adopt practices to effectively employ the treatment. The provision of guidance based upon early real-world experiences of licenced peanut OIT may help inform clinical practice and improve treatment outcomes.
Overlapping anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis with neuromyelitis optica spectrum disorders: a case report
Authors: Pan Jialin , Ovlyakulov Begench , Zhou Lili
Published: May 2022

Background

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis can coexist with neuromyelitis optica spectrum disorder (NMOSD). Patients with overlapping anti-NMDAR encephalitis with positive NMDAR antibodies and aquaporin 4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD are rare but should not be ignored.

Case presentation

This report describes a unique case of anti-NMDAR encephalitis coexisting with NMOSD. A 27-year-old male presented with blurred vision, cognitive impairment, psychosis, dysphagia, gait instability and urinary incontinence. Brain magnetic resonance imaging (MRI) showed abnormal signals in the right cerebellar hemisphere, temporal lobe, and corpus callosum. NMDAR antibodies were positive in the CSF. AQP4-IgG antibodies were positive in the serum. The patient's condition was stable following intravenous gamma globulin, corticosteroids, immunosuppressants and symptomatic treatments.

Conclusions

This case provides further evidence for the occurrence of anti-NMDAR encephalitis overlapping NMOSD with AQP4-IgG-seropositive in a Chinese patient. However, the mechanisms underlying the occurrence of double-positive antibodies remain elusive.
An improved algorithm for superresolution reconstruction of ancient murals with a generative adversarial network based on asymmetric pyramid modules
Authors: Ma Shang , Cao Jianfang , Li Zhaoxia , Chen Zeyu , Hu Xiaohui
Published: May 2022

Ancient Chinese murals are true portrayals of ancient Chinese life, but well-preserved murals are rare. Therefore, ancient mural preservation and repair are critical. To address the poor superresolution reconstruction of mural images with unclear textures and fuzzy details, we developed an improved generative adversarial network (GAN) algorithm based on asymmetric pyramid modules for ancient mural superresolution reconstruction. Asymmetric pyramid modules, which are composed of a series of dense compression units, were used to learn image features. To analyze the reconstructed image features, a perceptual loss function was integrated to optimize the model performance. The use of the improved algorithm for low-resolution mural images increased the image resolution while preserving their original feature details and textures, and the improvement effect was visually observed in terms of indices such as the peak signal-to-noise ratio and structural similarity. Compared with other superresolution-related algorithms, the proposed model increased the peak signal-to-noise ratio by 0.20–6.66 dB. The GAN-based mural superresolution reconstruction algorithm proposed in this study effectively improved the performance of reconstructed high-resolution mural images, which increases the significance of the reconstructed image for future research.
Scat piling and strong frugivory of the Balearic lizard, Podarcis lilfordi (Günther, 1874)
Authors: Pérez-Cembranos Ana , Pérez-Mellado Valentín
Published: May 2022

Background

In lacertid lizards from Mediterranean islands, frugivory is common, particularly under prey scarcity, a characteristic of small islands. In several populations, the diet of the Balearic lizard, Podarcis lilfordi, is extremely variable and includes fleshy fruits. However, frugivory is sporadic and there are very few examples of dominant fruit consumption.

Results

We describe the existence of an extraordinary fruit consumption of a single plant species, the juniper, Juniperus phoenicea, by the Balearic lizard, P. lilfordi. In addition, for the first time in Lacertidae, we describe the existence of scat piling in the population of these lizards inhabiting Cabrera Island (Balearic Islands, Spain). Scat piling was detected in an isolated location with hundreds of scats deposited by several individuals at a particular place.

Conclusions

The high population density of lizards at the island of Cabrera and the great versatility of foraging behavior of this species allows us to hypothesize that scat piles could act as an attractor for numerous individuals, that is, as inadvertent social information. If that hypothesis is correct, it would result in the concentration of several individuals foraging on a single or a few ripening plants. We cannot, however, rule out that individuals concentrated due to the scarcity of ripening plants in other areas, without any influence of the presence of several lizards, as attractors to the site. Our findings modify previous descriptions of the diet of the Balearic lizard in Cabrera made with smaller samples. In some places and periods of the year, frugivory on a single plant species can be extremely intense and only large sample sizes of scats allow to find these particular trends in the foraging ecology of insular lizards.
Copper-mediated DNA damage caused by purpurin, a natural anthraquinone
Authors: Kobayashi Hatasu , Mori Yurie , Iwasa Ryo , Hirao Yuichiro , Kato Shinya , Kawanishi Shosuke , Murata Mariko , Oikawa Shinji
Published: May 2022

Background

Purpurin (1,2,4-trihydroxy-9,10-anthraquinone), a natural red anthraquinone pigment, has historically been used as a textile dye. However, purpurin induced urinary bladder tumors in rats, and displayed a mutagenic activity in assay using bacteria and mammalian cells. Many carcinogenic dyes are known to induce bladder cancers via DNA adduct formation, but carcinogenic mechanisms of purpurin remain unknown. In this study, to clarify the mechanism underlying carcinogenicity of purpurin, copper-mediated DNA damage induced by purpurin was examined using 32P-labeled DNA fragments of human genes relevant to cancer. Furthermore, we also measured 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), an indicator of oxidative DNA damage, in calf thymus DNA.

Results

Purpurin plus Cu(II) cleaved 32P-labeled DNA fragments only under piperidine treatment, indicating that purpurin caused base modification, but not breakage of the DNA backbone. In the absence of Cu(II), purpurin did not induce DNA cleavage even with piperidine treatment. Purpurin plus Cu(II) caused piperidine-labile sites predominantly at G and some T residues. Bathocuproine, a Cu(I) chelator, completely prevented the occurrence of piperidine-labile sites, indicating a critical role of Cu(I) in piperidine-labile sites induced by purpurin plus Cu(II). On the other hand, methional, a scavenger of a variety of reactive oxygen species (ROS) and catalase showed limited inhibitory effects on the induction of piperidine-labile sites, suggesting that ROS could not be major mediators of the purpurin-induced DNA damage. Considering reported DNA adduct formation by quinone metabolites of several carcinogenic agents, quinone form of purpurin, which is possibly generated via purpurin autoxidation accompanied by Cu(I)/Cu(II) redox cycle, might lead to DNA adducts and piperidine-labile sites. In addition, we measured contents of 8-oxodG. Purpurin moderately but significantly increased 8-oxodG in calf thymus DNA in the presence of Cu(II). The 8-oxodG formation was inhibited by catalase, methional and bathocuproine, suggesting that Cu(I)-hydroperoxide, which was generated via Cu(I) and H2O2, caused oxidative DNA base damage.

Conclusions

We demonstrated that purpurin induces DNA base damage possibly mediated by Cu(I)/Cu(II) redox cycle both with and without ROS generation, which are likely to play an important role in its carcinogenicity.