bluuebunny/crossref_metadata_2025 huggingface dataset:
Champions for School Health—An NASN Initiative to Increase Vaccine Confidence, Equity, and Uptake in COVID-19 and School-Required Vaccinations: Part 1
Authors: D’Souza-Vazirani Deborah , Walsh Carol , Tanner Andrea L. , Clark Elizabeth , Griffin A. Renee , White Stephanye
Published: April 2023

The National Association of School Nurses (NASN) received a U.S.$2 million grant from Kaiser Permanente in January 2022 to increase confidence, equity, and uptake in the COVID-19 vaccine and other school required vaccinations in children ages 5 to 11 in Kaiser’s nine markets (eight states and the District of Columbia). NASN was partnered with the Institute of Educational Leadership (IEL) in this initiative to examine ways both organizations could learn how school nurses (SNs) and community schools (CSs) could collaborate to address the goals of this project. NASN gave 54 Implementation Grants in two funding cycles in 2022 and is co-funding two SN-CS collaboration projects with IEL. The Part 1 article provides an overview of the project’s goals, grant strategy and processes, grantee information, NASN created tools that resulted from this funding, and successful implementation of the project, which demonstrates NASN’s capacity for future similar projects.
Analysis of the impact of the “double reduction” policy on the educational processes of Chinese students studying in Europe
Authors: She Bibi , Ramasamy Siva Shankar , Loahavilai Piang-or
Published: April 2023

The relevance of the stated topic of scientific research is determined by the presence of many problems associated with the need to study the impact of the “double reduction” policy on the educational processes of Chinese students who are educated in Europe. This research work is aimed at studying the features of the “double reduction” policy, its advantages and disadvantages, as well as its impact on the educational processes of Chinese students studying in European educational institutions. The basis of the methodological approach in this research work is a qualitative combination of various theoretical research methods. In particular, analysis, synthesis, interpretation and generalization were used to study the “double reduction” policy, and the descriptive method and the comparative method were used to analyse the impact of this policy on the education of Chinese students studying in Europe. The results of this scientific study, as well as the conclusions formulated on their basis, are of practical value for teachers, methodologists, government officials and many other scientists who are actively involved in the topical problems of modern education in China, the issues of improving the quality of education and the overall improvement of the educational process in educational institutions in China.
Introduction: Is the time nigh for ecological security?
Authors: Beaumont Paul
Published: April 2023

Climate change and the ongoing destruction of the earth's ecosystems have increasingly been depicted as a security issue with the noble but not unproblematic goal engendering an urgent response. These climate and environmental security discourses have been extensively critiqued on both empirical and normative grounds. But is there an ethically defensible and even emancipatory alternative to envisioning the relationship between the environment and security? Matt McDonald in his new book - Ecological Security: Climate Change and the Construction of Security - argues that there is and lays out comprehensive normative framework for doing so. To interrogate McDonald's case for what he calls “Ecological Security”, this forum brings together four leading researchers from Anthropology, Geography, International Relations, and Peace and Sustainability Studies. While all contributors are broadly positive regarding goals of the book, each identifies weaknesses in the approach that move from suggestions on how refine the framework on the one hand to questioning whether the framework risks proving counter-productive on the other.
Democracy and Military Oversight in Crisis: The Failed Civilianisation of Indonesia’s Ministry of Defence
Authors: Mietzner Marcus
Published: April 2023

In 1998, Indonesia endeavoured to civilianise its defence department after decades of military-dominated rule. This civilianisation project was widely seen as a crucial element of democratisation itself. But the initiative ended in disillusionment: by 2014, the ministry was again placed under a conservative former general, and in 2019, it came under the control of Prabowo Subianto, an ambitious ex-military leader with strong ties to the pre-1998 autocratic regime. As a result, the reform drive in the ministry came to a halt, and civilians were marginalised again. This article argues that several factors account for this reform failure: first, the ministry’s long subordination to the military prior to 1998; second, the lack of will and power on the part of civilian ministers between 1999 and 2014 to pursue meaningful reforms; and third, a larger roll-back of democratic reforms beginning in the 2010s. Embedding these latest developments in a larger historical context, the article demonstrates that the defence ministry has been a barometer of Indonesia’s fluctuating democratic quality over time.
Strength Assessment After Reverse Shoulder Arthroplasty
Authors: Almeida Alexandre , Junior Aloir DO , Pante Samuel , Gobbi Luis F , Vicente Marcelo G , Oliboni Arivaldir B , Agostini Ana P
Published: April 2023

Objective

The main objective was to evaluate the anterior flexion force (AFF) and the lateral abduction force (LAF) of patients who underwent reverse shoulder arthroplasty (RSA) and to compare the measured force with that in a similar-age control group. The secondary objective was to identify prognostic factors for muscle strength recovery.

Methods

Forty-two shoulders that underwent primary RSA between September 2009 and April 2020 met the inclusion criteria and were called the arthroplasty group (AG). The control group (CG) consisted of 36 patients. The mean AFF and the mean LAF were evaluated with a digital isokinetic traction dynamometer.

Results

The average AFF found in the AG was 15 N, while in the CG, the average AFF was 21 N ( P < .001). The average LAF in the AG was 14 N (standard deviation [SD] 8 N), while in the CG the average LAF was of 19 N (SD 6 N) ( P = .002). All prognostic factors studied in the AG showed no statistical significance: dominance (AFF 0.697/LAF 0.883), previous rotator cuff repair surgery (AFF 0.786/LAF 0.821), Hamada radiological classification (AFF 0.343/LAF 0.857), magnetic resonance imaging (MRI) pre-operative evaluation of the quality of the teres minor (AFF 0.131/LAF 0.229), suture of the subscapularis at the end of the arthroplasty procedure (AFF 0.961/LAF 0.325) and postoperative complications (AFF 0.600/LAF 0.960).

Conclusion

The mean AFF was 15 N, and the mean LAF was 14 N. The comparison of AFF and LAF with a CG showed a 25% reduction in muscle strength. It was not possible to demonstrate prognostic factors for muscle strength recovery after RSA.
Ocular side effects of Trametinib and Dabrafenib: a case report
Authors: Tarım Bilge , Kılıç Meltem
Published: April 2023

A 53-year-old man who has stage 4 non-small cell lung carcinoma and treated with Dabrafenib-Trametinib combination chemotherapy; presented with decreased bilateral visual acuity. We checked out slit lamp examination, fundoscopy, optical coherence tomography and fundus fluorescein angiography. In slit lamp biomicroscopy; bilateral posterior synechiae, granulomatous keratic precipitates and + 4 cells in the anterior chamber were detected. Cystoid macular edema and subretinal fluid accumulation were revealed in optical coherence tomography. Dabrafenib and Trametinib treatments were discontinued and systemic methylprednisolone, topical corticosteroid and topical cyclopentolate were started. His best corrected visual acuity was increased from counting fingers from 2 m to 0,9 bilaterally and cystoid macular edema and serous retinal detachment were completely regressed as a result of systemic and topical corticosteroid treatment.
Genome-wide analysis of circular RNA-mediated ceRNA regulation in porcine skeletal muscle development
Authors: Yun Jiale , Huang Xiaoyu , Liu Chang , Shi Mingyue , Li Wenxia , Niu Jin , Cai Chunbo , Yang Yang , Gao Pengfei , Guo Xiaohong , Li Bugao , Lu Chang , Cao Guoqing
Published: April 2023

Background

As a diverse and abundant class of endogenous RNAs, circular RNAs (circRNAs) participate in various biological processes including cell proliferation and apoptosis. Nevertheless, few researchers have investigated the role of circRNAs in muscle development in cultivated pigs.

Results

In this study, we used RNA-seq to construct circRNA expression profiles in skeletal muscle of Jinfen White pigs at the age of 1, 90, and 180 days. Among the 16,990 identified circRNAs, 584 circRNAs were differentially expressed. Moreover, the enrichment analysis of DE circRNA host genes showed that they were mainly involved in muscle contraction, muscle organ development and muscle system processes, as well as AMPK and cAMP-related signal pathways. We also constructed a circRNA–miRNA–mRNA co-expression network to find key circRNAs which many involved in the regulation of porcine skeletal muscle development through the competitive endogenous RNA (ceRNA) mechanism. It is noteworthy that circ_0018595/miR-1343/PGM1 axis may play a regulatory role in the development of porcine skeletal muscle.

Conclusions

This study identified the circRNAs and present the circRNA expression profile in the development of pigs, revealed that DE circRNA host genes participate in different cell fates and enriched the porcine ceRNA network. Thus, this work will become a valuable resource for further in-depth study of the regulatory mechanism of circRNA in the development of porcine skeletal muscle.
Genome-wide association study of leaf-related traits in tea plant in Guizhou based on genotyping-by-sequencing
Authors: Chen Yanjun , Niu Suzhen , Deng Xinyue , Song Qinfei , He Limin , Bai Dingchen , He Yingqin
Published: April 2023

Background

Studying the genetic characteristics of tea plant (Camellia spp.) leaf traits is essential for improving yield and quality through breeding and selection. Guizhou Plateau, an important part of the original center of tea plants, has rich genetic resources. However, few studies have explored the associations between tea plant leaf traits and single nucleotide polymorphism (SNP) markers in Guizhou.

Results

In this study, we used the genotyping-by-sequencing (GBS) method to identify 100,829 SNP markers from 338 accessions of tea germplasm in Guizhou Plateau, a region with rich genetic resources. We assessed population structure based on high-quality SNPs, constructed phylogenetic relationships, and performed genome-wide association studies (GWASs). Four inferred pure groups (G-I, G-II, G-III, and G-IV) and one inferred admixture group (G-V), were identified by a population structure analysis, and verified by principal component analyses and phylogenetic analyses. Through GWAS, we identified six candidate genes associated with four leaf traits, including mature leaf size, texture, color and shape. Specifically, two candidate genes, located on chromosomes 1 and 9, were significantly associated with mature leaf size, while two genes, located on chromosomes 8 and 11, were significantly associated with mature leaf texture. Additionally, two candidate genes, located on chromosomes 1 and 2 were identified as being associated with mature leaf color and mature leaf shape, respectively. We verified the expression level of two candidate genes was verified using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and designed a derived cleaved amplified polymorphism (dCAPS) marker that co-segregated with mature leaf size, which could be used for marker-assisted selection (MAS) breeding in Camellia sinensis.

Conclusions

In the present study, by using GWAS approaches with the 338 tea accessions population in Guizhou, we revealed a list of SNPs markers and candidate genes that were significantly associated with four leaf traits. This work provides theoretical and practical basis for the genetic breeding of related traits in tea plant leaves.
Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer
Authors: Yu Jie , Sun Qi , Hui Yi , Xu Jinping , Shi Pancheng , Chen Yu , Chen Yunzhao
Published: April 2023

Background

Colorectal cancer (CRC) is a common disease threatening human lives worldwide, and vitamin D receptor (VDR) contributes protective roles in this disease. However, the molecular mechanisms underlying VDR protection in CRC progression require further investigation.

Methods

In this study, we statistically analyzed the relationship between VDR expression and CRC development in patients and detected invasion and apoptosis in CRC cells with VDR overexpression and interference. We also detected the expression of key genes involved in Wnt/β-catenin signalling (β-catenin, lymphoid enhancer factor (LEF)-1 and cyclin D1) in SW480 cells and nude mice injected with VDR-overexpressing SW480 cells and observed tumour development. Additionally, we performed Co-immunoprecipitation (Co-IP) and glutathione-S-transferase (GST) pull-down assays to identify the protein interactions of VDR with β-catenin, dual luciferase (LUC) and chromatin immunoprecipitation (ChIP) to detect the activation of LEF-1 by VDR.

Results

The VDR level was closely related to the development and prognosis of CRC patients. VDR overexpression inhibited invasion but promoted apoptosis in cancer cells. β-catenin shRNA contributed oppositely to cancer cell activity with VDR shRNA. Additionally, VDR interacted with β-catenin at the protein level and blocked its nuclear accumulation. VDR regulated the expression of β-catenin, cyclin D1 and LEF-1 and directly activated LEF-1 transcription in vitro. Furthermore, nude mice injected with VDR-overexpressing SW480 cells revealed suppression of tumour growth and decreased expression of β-catenin, cyclin D1 and LEF-1.

Conclusions

This study indicated that VDR protected against CRC disease in humans by inhibiting Wnt/β-catenin signalling to control cancer cell invasion and apoptosis, providing new evidence to explore VDR biomarkers or agonists for CRC patient diagnosis and treatment.
Gender differences in metabolic syndrome and its components in southern china using a healthy lifestyle index: a cross-sectional study
Authors: Ye Ying , Zhou Qiuhong , Dai Weiwei , Peng Hua , Zhou Shi , Tian Huixia , Shen Lu , Han Huiwu
Published: April 2023

Background

Lifestyle changes are important for the prevention and management of metabolic syndrome (MetS), but studies that focus on gender differences in the lifestyle risk factors of MetS are limited in China. This research aimed to generate a healthy lifestyle index (HLI) to assess the behavioral risk factors of MetS and its components, and to explore the gender differences in HLI score and other influencing factors of MetS.

Methods

A convenience sample of 532 outpatients were recruited from a general hospital in Changsha, China. The general information and HLI scores [including physical activity (PA), diet, smoking, alcohol use, and body mass index (BMI)] of the subjects were collected through questionnaires, and each patient’s height, weight, waist circumference, and other physical signs were measured. Logistic regression analysis was used to analyze the risk factors of MetS and its components.

Results

The prevalence of MetS was 33.3% for the whole sample (46.3% in males and 23.3% in females). The risk of MetS increased with age, smoking, unhealthy diet, and BMI in males and with age and BMI in females. Our logistic regression analysis showed that lower HLI (male: OR = 0.838,95%CI = 0.757–0.929; female: OR = 0.752, 95%CI = 0.645–0.876) and older age (male: OR = 2.899, 95%CI = 1.446–5.812; female: OR = 4.430, 95%CI = 1.640–11.969) were independent risk factors of MetS, for both sexes.

Conclusion

Low levels of HLI and older ages were independent risk factors of MetS in both males and females. The association between aging and MetS risk was stronger in females, while the association between unhealthy lifestyles and MetS risk was stronger in males. Our findings reinforced the expected gender differences in MetS prevalence and its risk factors, which has implications for the future development of gender-specific MetS prevention and intervention programs.
Early childhood developmental status and its associated factors in Bangladesh: a comparison of two consecutive nationally representative surveys
Authors: Hasan Mohammad Nayeem , Babu Md. Rashed , Chowdhury Muhammad Abdul Baker , Rahman Mohammad Meshbahur , Hasan Nafiul , Kabir Russell , Uddin Md Jamal
Published: April 2023

Background

Inadequate cognitive and socio-emotional development in children leads to physical and mental illness. We aimed to investigate the status of early childhood development (ECD) and its associated factors. Additionally, aimed to compare the changes of significantly associated factors using two multiple indicator cluster surveys (MICS) in Bangladesh.

Methods

We used data from the Multiple Indicator Cluster Surveys (MICS) 2012 and 2019 nationally representative surveys. A total of 17,494 children aged 36–59 months were included in the analysis. The outcome variable was ECD status: either developmentally on-track or not. We used bivariable analysis and crude and adjusted multivariable logistic models to assess the ECD status and its associated factors.

Results

Comparing both MICS surveys, the overall and individual domains of ECD status improved from 2012 (65.46%) to 2019 (74.86%), and the indicators of child literacy-numeracy domain improved from 21.2 to 28.8%, physical domain improved from 92.2 to 98.4%, and social-emotional domain improved from 68.4 to 72.7%. The learning approach domain was 87.5% in 2012 and increased to 91.4% in 2019. According to the adjusted logistic model in both surveys (2012 and 2019), the age of 4 years had an adjusted odds ratio (AOR) of 1.61 and 1.78 times higher developmentally on track than the age of 3. Female children were 1.42 (in 2012) and 1.44 (in 2019) times more developmentally on track than males. Compared to mothers with only primary education, children raised by mothers with secondary or higher education were 1.77 and 1.50 times more on track in their development. Moreover, Children from affluent families had 1.32- and 1.26 times higher odds- on track than those from the poorest families. Families with books had 1.50 and 1.53 times higher developmentally on track than their counterparts.

Conclusion and recommendation

In summary, our study shows that the overall ECD status improved between MICS 2012 and MICS 2019. Important factors influence ECD status, including early childhood education programs, families’ possession of children’s books, mothers’ educational level, and wealth index. The findings of our study will help making necessary public health-related initiatives in Bangladesh to improve ECD program.
Complications and prognosis of primary thoracic and lumbar giant cell tumors treated by total tumor resection
Authors: Liu Jiacheng , Hu Panpan , Zhou Hua , Wang Ben , Liu Xiaoguang , Wu Fengliang , Li Yan , Liu Xiao , Dang Lei , Tang Yanchao , Li Zihe , Liu Zhongjun , Wei Feng
Published: April 2023

Background

Spinal giant cell tumor (SGCT) is a relatively rare primary tumor. En bloc resection is the preferred surgical procedure for it due to its aggressiveness, meanwhile leading to more complications. We reported the characteristics of perioperative complications and local control of total tumor resection including en bloc resection and piecemeal resection for primary thoracic and lumbar spinal giant cell tumors in a single center over 10 years.

Methods

This is a retrospective cross-sectional and cohort study. Forty-one consecutive patients with SGCTs who underwent total tumor resection from 2010 to 2020 at our institution and were followed up for at least 24 months were reviewed. Surgery data, complication characteristics and local tumor control were collected and compared by different surgical procedure.

Results

Forty-one patients were included, consisting of 18 males and 23 females, with a mean age of 34.2 years. Thirty-one had thoracic vertebra lesions, and 10 had lumbar vertebra lesions. Thirty-five patients were primary cases, and 6 patients were recurrent cases. Eighteen patients were treated by total en bloc spondylectomy (TES), 12 patients underwent en bloc resection according to WBB surgical system, and 11 patients underwent piecemeal resection. The average surgical time was 498 min, and the mean estimated blood loss was 2145 ml. A total of 58 complications were recorded, and 30 patients (73.2%) had at least one perioperative complication. All patients were followed up after surgery for at least 2 years. A total of 6 cases had postoperative internal fixation failure, and 4 cases presented local tumor recurrence (9.8%).

Conclusions

Although the surgical technique is difficult and accompanied by a high rate of perioperative complications, en bloc resection can achieve favorable local control in SGCT. When it is too difficult to complete en bloc resection, thoroughly piecemeal resection without residual is also acceptable, given the relatively low recurrence rate.
Treatment outcomes of applying external fixator on distal radius fractures: a randomized clinical trial to compare between two directions of force exertion in parallel to radius shaft and perpendicular to the distal radius articular surface
Authors: Jafari Davood , Birjandinejad Ali , Daliri Mahla , Emami Kimia , Moradi Ali
Published: April 2023

Background

External fixation has been one of the conventional managements of unstable distal radius fracture. The main aim of this paper is to compare two methods of applying distractive force along the radius shaft versus perpendicular to the distal radius articular surface.

Design

Sixty patients with unstable distal radius fracture were included in present clinical trial and randomized in two groups, using block randomization method. In group A (first arm), distraction force was exerted parallel to the radius shaft. In group B (second arm), the external fixator was adjusted based on radial and palmar tilt of the mean population healthy wrist so that distraction was exerted perpendicular to the wrist articular surface.

Methods

Radiological and clinical parameters were evaluated in both groups of patients pre-operatively, immediately after surgery, and 6 weeks post-operatively. We also followed up patients clinically at 12 weeks after surgery. Patient-Rated Wrist Evaluation (PRWE), Mayo wrist score, and Quick Disabilities of the Arm, Shoulder and Hand (DASH) questionnaires were used in order to assess patients’ clinical and functional states.

Results

The method used in group B resulted in better improvement of palmar tilt both immediately (P = 0.007) and at 6 weeks follow up (P = 0.013) post-operatively in comparison with patients in group A. Radius height and radial inclination were also better restored when using the proposed modified method (P = 0.001 and < 0.001, respectively). There was no difference in any of clinical results (range of motion, grip strength, PRWE, Mayo, and DASH scores) between two groups of study, 12 weeks after surgery.

Conclusion

Applying distractive force perpendicular to the distal radius articular surface seems to improve some radiological outcomes, probably due to better reduction maintenance, when compared with the technique of applying distraction force along distal radius shaft axis.

Level of Evidence

Level I (clinical trial study).

Trial registration

This study is registered at Iranian Registry of Clinical Trials (IRCT) with approval code of IRCT20200313046759N1.
#OMFSurgery: analyzing the use of social media applications in oral and maxillofacial surgery resident training
Authors: Seifert Lukas B. , Becker Philipp , Pabst Andreas , Sander Anna K. , Schneider Josephine , Schorn Lara , Zeller Alexander , Hoffmann Jürgen , Thiem Daniel G. E.
Published: April 2023

Background

Despite its increasing popularity, to our knowledge the use of social media applications (SM) for residents’ training in Oral and Maxillofacial Surgery (OMFS) has not been investigated yet. The aim of this study was to evaluate the use of SM applications by OMFS residents for post-graduate training in Germany.

Methods

For explorative assessment, an online questionnaire containing 27 questions about the current use of SM for resident training was sent to OMFS residents in Germany.

Results

Sixty-four colleagues participated to the study. Thirty-four participants (54%) responded to regularly use those platforms mainly for OMFS-related content. YouTube (65%, n = 37), Instagram (48%, n = 27), ResearchGate (25%, n = 14) and WhatsApp (16%, n = 9) were the most popular platforms. (Surgical) videos (97%, n = 59), pictures and graphics (82%, n = 50) were the mainly accessed contents. Forty-four participants (69%) stated that SM substantially contributed to their OMFS training. Dentoalveolar surgery and implantology (66%, n = 35) and aesthetic facial surgery (55%, n = 29) content contributed most to OMFS resident training. Fifty-one participants (80%) recommended an official SM account of the DGMKG.

Conclusions

SM is frequently used by OMFS residents for the consumption of training-related content. There is an imbalance toward dentoalveolar and facial aesthetic surgery regarding the presented content. Academic institutions and societies should complement their educational activities to not miss this emerging educational innovation. Official SM content by academic institutions and societies could contribute to the existing educational activities.
Effect of the vertical facial pattern on the developmental relationship between the nasal bone and maxillary central incisors
Authors: Shi Jianwei , Al-Ak’hali Mohammed Sultan , Cai Dingjun , Guo Qiutong , Cao Yuming , Alhammadi Maged S. , Mashrah Mubarak Ahmed , Yang Yang
Published: April 2023

Background

This study aimed to investigate the effect of vertical facial patterns on the developmental relationship between the nasal bone and maxillary central incisors.

Methods

In this retrospective comparative study, the lateral cephalograms of 213 subjects (51 Males, 162 Females) with skeletal Class I malocclusion (aged 18–32 years) were classified into three equal groups: (1) hyperdivergent, (2) normodivergent, and (3) hypodivergent facial patterns based on the mandibular plane inclination (S–N/Go-Me). Several sets of measurements were extracted: (1) gradient and length of the nasal bone and maxillary central incisor, (2) the distance from apex and root of the nasal bone, and (3) maxillary central incisor to the true perpendicular from the digitized lateral cephalograms. The significance level was considered atP < 0.05.

Results

The inclination angle and length between nasal bone and maxillary central incisor were positively correlated independent of vertical facial type. The inclination angle of the nasal bone in the hypodivergent group was significantly larger than the other two vertical facial patterns. The inclination angle of the maxillary central incisor increased successively in the hyperdivergent, normodivergent, and hypodivergent groups. The length of the nasal bone in the hyperdivergent group was significantly longer than that in the hypodivergent and normodivergent groups. The maxillary central incisor length in the hyperdivergent group was significantly longer than in the hypodivergent group.

Conclusion

A correlation between nasal bone and maxillary central incisors during the growth and development of the maxillofacial region was found. In Class I malocclusion subjects, hypodivergent patients were more likely to have a prominent and relatively short nasal bone and maxillary central incisors and vice versa.
In vitro anti-yeast activity, kinetics and mechanism of action of essential oils from two cameroonian medicinal plants
Authors: Tchinang Flore Tatiana Kemegni , Ndoyé Foé Florentine Marie-Chantal , Keumoe Rodrigue , Zeuko’o Elisabeth Menkem , Fekam Fabrice Boyom , Etoa François-Xavier
Published: April 2023

Background

Treatment of Candida infections have become increasingly difficult due to antifungal drug resistance, which has drawn attention toward the search for innovative and effective drugs. This study aimed to assess the activity of essential oils (EOs) from Pentadiplandra brazzeana Baillon (PB) root and Drypetes gossweileri S. Moore (DG) stem bark against Candida albicans and Candida parapsilopsis strains, and determine their antifungal mechanism when tested alone or combined.

Methods

The anticandidal activity of the EOs using the checkerboard format was assessed using the broth micro-dilution technique. The checkerboard microtiter test was performed to evaluate the interaction of the EOs. The in vitro pharmacodynamics of the EOs alone or combined, using time-kill assays, following the chequerboard technique were evaluated. The anticandidal mode of action of these EOs, combined or not, was investigated using the sorbitol protection assay, and the ergosterol binding assay. Differences (p < 0.05) between the experimental and the control groups were evaluated using one way analysis of variance (ANOVA) followed by Tukey’s test for multiple comparisons.

Results

Essential oils (EOs) from Drypetes gossweileri (DG) stem bark showed activity with MIC value of 62.5 µg/mL against Candida albicans and Candida parapsilopsis, whereas EOs from Pentadiplandra brazzeana (PB) root exhibited MICs of 125 µg/mL and 250 µg/mL against the respective yeasts. The EOs were fungicidal with synergism on C. parapsilopsis and additivity on C. albicans, with 2 to 64-fold drop in MIC values. The MIC combination of 31.25/7.81 µg/mL and 1.95/31.25 µg/mL (DG/PB EOs) required 20 and 18 h of exposure, respectively to effectively kill 99.9% of the inoculum. This fungicidal effect was accompanied by alteration of the cell walls and membranes of yeasts.

Conclusion

The potency of the EOs combinations indicates further directions in their investigation as potential anticandidal agents.
The development of the Dutch “National model integrated care for childhood overweight and obesity”
Authors: Halberstadt J. , Koetsier L. W. , Sijben M. , Stroo J. , van der Velde M. , van Mil E. G. A. H. , Seidell J. C.
Published: April 2023

Background

Childhood obesity is a chronic disease with negative physical and psychosocial health consequences. To manage childhood overweight and obesity, integrated care as part of an integrated approach is needed. To realise implementation of this integrated care, practical guidance for policy and practice is needed. The aim of this study is to describe the development of a Dutch national model of integrated care for childhood overweight and obesity and accompanying materials for policy and practice.

Methods

The development of the national model was led by a university-based team in collaboration with eight selected Dutch municipalities who were responsible for the local realisation of the integrated care and with frequent input from other stakeholders. Learning communities were organised to exchange knowledge, experiences and tools between the participating municipalities.

Results

The developed national model describes the vision, process, partners and finance of the integrated care. It sets out a structure that provides a basis for local integrated care that should facilitate support and care for children with overweight or obesity and their families. The accompanying materials are divided into materials for policymakers to support local realisation of the integrated care and materials for healthcare professionals to support them in delivering the needed support and care.

Conclusions

The developed national model and accompanying materials can contribute to improvement of support and care for children with overweight or obesity and their families, and thereby help improve the health, quality of life and societal participation of these children. Further implementation of the evidence- and practice-based integrated care while evaluating on the way is needed.
Mental health service use and associated predisposing, enabling and need factors in community living adults and older adults across Canada
Authors: Vasiliadis Helen-Maria , Spagnolo Jessica , Fleury Marie-Josée , Gouin Jean-Philippe , Roberge Pasquale , Bartram Mary , Grenier Sébastien , Shen-Tu Grace , Vena Jennifer E. , Wang JianLi
Published: April 2023

Objectives

Using Andersen’s model of health care seeking behavior, we examined the predisposing, enabling, and need factors associated with mental health service use (MHSU) during the first wave of the COVID-19 pandemic across Canada.

Methods

The sample included n = 45,542 participants in the 5 established regional cohorts of the Canadian Partnership for Tomorrow’s Health (CanPath) and who responded to the CanPath COVID-19 health survey (May-December 2020), with complete data on MHSU. Multivariable logistic regression analyses were carried out to study MHSU as a function of predisposing, enabling, and need factors. Analyses were stratified by regional cohort.

Results

Among the need factors, individuals reporting moderate/severe symptoms of depression and anxiety and poorer self-rated mental health were more likely to report MHSU. Among the enabling factors, receipt of informational/financial/practical support was associated with increased MHSU. While income was not consistently associated with MHSU, reported decrease in income was marginally associated with reduced MHSU. Among the predisposing factors, identifying as female or other gender minority was associated with increased MHSU, as was the presence of past-year cannabis use. In contrast, older age and alcohol consumption were associated with reduced MHSU.

Conclusion

Need factors were consistently associated with MHSU. Although income inequities in MHSU were not observed, changes such as reduced income during the pandemic may lead to barriers in accessing mental health services. Future research should focus on better identifying contextual enabling factors and policies that overcome financial barriers to MHSU.
New insights into posttranslational modifications of proteins during bull sperm capacitation
Authors: Mostek-Majewska Agnieszka , Majewska Anna , Janta Anna , Ciereszko Andrzej
Published: April 2023

Background

Due to the unique nature of spermatozoa, which are transcriptionally and translationally silent, the regulation of capacitation is based on the formation of posttranslational modifications of proteins (PTMs). However, the interactions between different types of PTMs during the capacitation remain unclear. Therefore, we aimed to unravel the PTM-based regulation of sperm capacitation by considering the relationship between tyrosine phosphorylation and reversible oxidative PTMs (oxPTMs), i.e., S-nitrosylation and S-glutathionylation. Since reversible oxPTMs may be closely related to peroxyredoxin (PRDX) activity, the second aim was to verify the role of PRDXs in the PTM-based regulation of capacitation.

Methods

Cryopreserved bull sperm were capacitated in vitro with or without PRDX inhibitor. Qualitative parameters of sperm and symptoms characteristic of capacitation were analyzed. Posttranslational protein modifications (S-nitrosylation, S-glutathionylation, tyrosine phosphorylation) were investigated at the cellular level (flow cytometry, fluorescence microscopy) and at the proteomic level (fluorescent gel-based proteomic approach).

Results

Zona-pellucida binding proteins (ACRBP, SPAM1, ZAN, ZPBP1 and IZUMO4) were particularly rich in reversible oxPTMs. Moreover, numerous flagellar proteins were associated with all analyzed types of PTMs, which indicates that the direction of posttranslational modifications was integrated. Inhibition of PRDX activity during capacitation caused an increase in S-nitrosylation and S-glutathionylation and a decrease in tyrosine phosphorylation. Inhibition of PRDXs caused GAPDHS to undergo S-glutathionylation and the GSTO2 and SOD2 enzymes to undergo denitrosylation. Moreover, PRDX inhibition caused the AKAP proteins to be dephosphorylated.

Conclusions

Our research provides evidence that crosstalk occurs between tyrosine phosphorylation and reversible oxPTMs during bull sperm capacitation. This study demonstrates that capacitation triggers S-nitrosylation and S-glutathionylation (and reverse reactions) of zona-pellucida binding proteins, which may be a new important mechanism that determines the interaction between sperms and oocytes. Moreover, TCA-related and flagellar proteins, which are particularly rich in PTMs, may play a key role in sperm capacitation. We propose that the deglutathionylation of ODFs and IZUMO4 proteins is a new hallmark of bull sperm capacitation. The obtained results indicate a relationship between PRDX activity and protein phosphorylation, S-glutathionylation and S-nitrosylation. The activity of PRDXs may be crucial for maintaining redox balance and for providing proper PKA-mediated protein phosphorylation during capacitation.
Recent advances and future challenges of tumor vaccination therapy for recurrent glioblastoma
Authors: Zhao Binghao , Wu Jiaming , Li Huanzhang , Wang Yuekun , Wang Yaning , Xing Hao , Wang Yu , Ma Wenbin
Published: April 2023

Glioblastoma (GBM) is the most malignant CNS tumor with a highest incidence rate, and most patients would undergo a recurrence. Recurrent GBM (rGBM) shows an increasing resistance to chemotherapy and radiotherapy, leading to a significantly poorer prognosis and the urgent need for novel treatments. Immunotherapy, a rapidly developing anti-tumor therapy in recent years, has shown its potential value in rGBM. Recent studies on PD-1 immunotherapy and CAR-T therapy have shown some efficacy, but the outcome was not as expected. Tumor vaccination is the oldest approach of immunotherapies, which has returned to the research focus because of the failure of other strategies and subversive understanding of CNS. The isolation effect of blood brain barrier and the immunosuppressive cell infiltration could lead to resistance existing in all phases of the anti-tumor immune response, where novel tumor vaccines have been designed to overcome these problems through new tumor antigenic targets and regulatory of the systematic immune response. In this review, the immunological characteristics of CNS and GBM would be discussed and summarized, as well as the mechanism of each novel tumor vaccine for rGBM. And through the review of completed early-phase studies and ongoing large-scale phase III clinical trials, evaluation could be conducted for potential immune response, biosecurity and initial clinical outcome, which further draw a panorama of this vital research field and provide some deep thoughts for the prospective tendency of vaccination strategy.
FAP-targeted CAR-T suppresses MDSCs recruitment to improve the antitumor efficacy of claudin18.2-targeted CAR-T against pancreatic cancer
Authors: Liu Yifan , Sun Yansha , Wang Peng , Li Songling , Dong Yiwei , Zhou Min , Shi Bizhi , Jiang Hua , Sun Ruixin , Li Zonghai
Published: April 2023

Purpose

The claudin 18.2 (CLDN18.2) antigen is frequently expressed in malignant tumors, including pancreatic ductal adenocarcinoma (PDAC). Although CLDN18.2-targeted CAR-T cells demonstrated some therapeutic efficacy in PDAC patients, further improvement is needed. One of the major obstacles might be the abundant cancer-associated fibroblasts (CAFs) in the PDAC tumor microenvironment (TME). Targeting fibroblast activation protein (FAP), a vital characteristic of CAFs provides a potential way to overcome this obstacle. In this study, we explored the combined antitumor activity of FAP-targeted and CLDN18.2-targeted CAR-T cells against PDAC.

Methods

Novel FAP-targeted CAR-T cells were developed. Sequential treatment of FAP-targeted and CLDN18.2-targeted CAR-T cells as well as the corresponding mechanism were explored in immunocompetent mouse models of PDAC.

Results

The results indicated that the priorly FAP-targeted CAR-T cells infusion could significantly eliminate CAFs and enhance the anti-PDAC efficacy of subsequently CLDN18.2-targeted CAR-T cells in vivo. Interestingly, we observed that FAP-targeted CAR-T cells could suppress the recruitment of myeloid-derived suppressor cells (MDSCs) and promote the survival of CD8+ T cells and CAR-T cells in tumor tissue.

Conclusion

In summary, our finding demonstrated that FAP-targeted CAR-T cells could increase the antitumor activities of sequential CAR-T therapy via remodeling TME, at least partially through inhibiting MDSCs recruitment. Sequential infusion of FAP-targeted and CLDN18.2-targeted CAR-T cells might be a feasible approach to enhance the clinical outcome of PDAC.
Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13
Authors: Guo Jiahao , Han Xiaoyang , Li Jie , Li Zhefeng , Yi Junjie , Gao Yan , Zhao Xiaoting , Yue Wentao
Published: April 2023

Background

Metastasis, the leading cause of cancer-related death in patients diagnosed with ovarian cancer (OC), is a complex process that involves multiple biological effects. With the continuous development of sequencing technology, single-cell sequence has emerged as a promising strategy to understand the pathogenesis of ovarian cancer.

Methods

Through integrating 10 × single-cell data from 12 samples, we developed a single-cell map of primary and metastatic OC. By copy-number variations analysis, pseudotime analysis, enrichment analysis, and cell–cell communication analysis, we explored the heterogeneity among OC cells. We performed differential expression analysis and high dimensional weighted gene co-expression network analysis to identify the hub genes of C4. The effects of RAB13 on OC cell lines were validated in vitro.

Results

We discovered a cell subcluster, referred to as C4, that is closely associated with metastasis and poor prognosis in OC. This subcluster correlated with an epithelial–mesenchymal transition (EMT) and angiogenesis signature and RAB13 was identified as the key marker of it. Downregulation of RAB13 resulted in a reduction of OC cells migration and invasion. Additionally, we predicted several potential drugs that might inhibit RAB13.

Conclusions

Our study has identified a cell subcluster that is closely linked to metastasis in OC, and we have also identified RAB13 as its hub gene that has great potential to become a new therapeutic target for OC.
Adherence, helpfulness and barriers to treatment in juvenile idiopathic arthritis – data from a German Inception cohort
Authors: Kirchner Sabine , Klotsche Jens , Liedmann Ina , Niewerth Martina , Feldman Debbie , Dressler Frank , Foeldvari Ivan , Foell Dirk , Haas Johannes-Peter , Horneff Gerd , Hospach Anton , Kallinich Tilmann , Kuemmerle-Deschner J. B. , Moenkemoeller Kirsten , Weller-Heinemann Frank , Windschall Daniel , Minden Kirsten , Sengler Claudia
Published: April 2023

Objectives

To develop and evaluate German versions of the Parent Adherence Report Questionnaire (PARQ) and Child Adherence Report Questionnaire (CARQ) and to evaluate adherence in patients with juvenile idiopathic arthritis (JIA).

Methods

The PARQ and CARQ were translated into German, cross-culturally adapted and administered to patients (age ≥ 8 years) and their parents enrolled in the Inception Cohort Study of newly diagnosed JIA patients (ICON).

The psychometric issues were explored by analyzing their test–retest reliability and construct validity.

Results

Four hundred eighty-one parents and their children with JIA (n = 465) completed the PARQ and CARQ at the 4-year follow-up. Mean age and disease duration of patients were 10.1 ± 3.7 and 4.7 ± 0.8 years, respectively. The rate of missing values for PARQ/CARQ was generally satisfactory, test-retesting showed sufficient reliability. PARQ/CARQ mean child ability total scores (0–100, 100 = best) for medication were 73.1 ± 23.3/76.5 ± 24.2, for exercise: 85.6 ± 16.5/90.3 ± 15.0, for splints: 72.9 ± 24.2/82.9 ± 16.5. Construct validity was supported by PARQ and CARQ scores for medications, exercise and splints showing a fair to good correlation with the Global Adherence Assessment (GAA) and selected PedsQL scales. Adolescents showed poorer adherence than children. About one third of the parents and children reported medication errors. Perceived helpfulness was highest for medication, and adverse effects were reported the greatest barrier to treatment adherence.

Conclusions

The German versions of the PARQ and CARQ appear to have a good reliability and sufficient construct validity. These questionnaires are valuable tools for measuring treatment adherence, identifying potential barriers and evaluating helpfulness of treatments in patients with JIA.
Post-traumatic stress disorder among Iranian women with genital mutilation: a cross-sectional study
Authors: Abdollahzadeh Mahsa , Nourizadeh Roghaiyeh , Jahdi Niloufar Sattarzadeh
Published: April 2023

Background

The conflicting evidence on the relationship between female genital mutilation/ cutting (FGM/C) and post-traumatic stress disorder (PTSD) may be due to the differences in the prevalence and type of FGM/C in different societies. The present study aimed to assess the prevalence and severity of PTSD and its associated factors among Iranian women with genital mutilation.

Methods

This cross-sectional study was performed on 155 women with genital mutilation aged 18–45 years referred to the health centers in Mahabad, located in west of Iran from October 2020 to April 2021. The participants were selected using convenience sampling method. After obtaining the informed consent form from the participants, the first researcher in the presence of a gynecologist determined the type of genital mutilation through the gynecological examination. The data were collected using demographic and obstetric characteristics and post-traumatic stress disorder checklist (PCL5) and analyzed using SPSS21 software. Further, independent t-test, ANOVA, Pearson correlation coefficient, and multivariate linear regression were used.

Result

All 155 women (100%) had type 1 genital mutilation. Six women (3.9%) had PTSD. The mean (SD) score of the PTSD symptoms among the women was 27.73 (6.79) in the attainable score of 0–80. The age at FGM/C, level of education, and type of residence were considered as the predictors of the severity of the symptoms of PTSD, as explaining 48.1% of the variance.

Conclusion and recommendation

In the present study, the prevalence and severity of PTSD among the participants were relatively low, which may be due to convenience sampling method used in the study, the limited injury in genitalia, and the social acceptance of the practice. The results indicated that the severity of the PTSD symptoms enhanced by increasing age at FGM/C and decreasing socio-economic levels. It is recommended to conduct the similar studies among women with other types of FGM/C.