bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of educational attainment on birthrate in Japan: an analysis using the census and the vital statistics from 2000 to 2020
Authors: Okui Tasuku
Published: March 2024

Background

In Japan, difference in birth rates depending on educational attainment has not been investigated. This study aimed to reveal birth rates in Japan depending on the highest level of educational attainment and their trends over the years using nationwide government statistics data.

Methods

Individual-level data from Vital Statistics and the Census from 2000, 2010, and 2020 were used for birth and population data, respectively. Data linkage was conducted for males and females in the Census and fathers and mothers in the Vital Statistics using information about gender, household, nationality, marital status, birth year, birth month, prefecture, and municipality for individuals. The birth rate was calculated by gender, a five-year age group, the highest level of educational attainment achieved, and year. In addition, the slope index of inequality (SII) and relative index of inequality (RII) were calculated to evaluate the degree of inequality in birth rates, depending on the educational attainment.

Results

Birth rates were higher in persons with lower educational attainment compared to those with a higher educational attainment among males and females in their twenties, while they tended to be higher in persons with higher educational attainment among those in their thirties and forties. Additionally, an increase in the birth rate from 2000 to 2020 was the largest in university graduates among males aged 25–49 years and women aged 30–49 years, and a decrease in the birth rate was the smallest in university graduates among males and females aged 20–24 years. As a result, SII and RII increased from 2000 to 2020 among males and females in their thirties and forties.

Conclusions

In conclusion, persons with higher educational attainment tended to have a relatively favorable trend in the birth rate compared with persons with lower educational attainment in recent decades. It suggested that enhanced administrative support for individuals with lower educational attainment or lower socioeconomic status may be required to ameliorate the declining birth rate in Japan.
The relationship between duration of infertility and clinical outcomes of intrauterine insemination for younger women: a retrospective clinical study
Authors: Huang Chenyang , Shi Qingqing , Xing Jun , Yan Yuan , Shen Xiaoyue , Shan Huizhi , Sun Haixiang , Mei Jie
Published: March 2024

Background

The objective of this research was to elucidate the association between the length of infertility and the outcomes of intrauterine insemination (IUI) in women of varying ages - a topic that has been the subject of investigation for numerous years, yet lacks a definitive consensus.

Methods

A retrospective cohort investigation involving 5268 IUI cycles was undertaken at the Reproductive Medicine Center of Nanjing Drum Tower Hospital from 2016 to 2022. Utilizing the smooth fitting curve along with threshold and saturation effect analysis, the correlation between infertility duration and IUI clinical pregnancy rates was discerned. Moreover, patients were bifurcated into two cohorts based on their respective infertility durations. A secondary examination was also performed employing propensity-score matching to mitigate the impact of confounding variables. Subsequent threshold and saturation effect analysis was carried out across various subgroups, segmented on the basis of age differentiation.

Results

When the duration of infertility was more than 5 years, the clinical pregnancy rate decreased with the increase of infertility duration (aOR: 0.894, 95%CI: 0.817–0.991, p = 0.043). The multivariate regression analysis suggested that longer duration of infertility (≥ 5 years) was significantly correlated with the lower clinical pregnancy rate (aOR: 0.782, 95% CI: 0.643–0.950, p = 0.01). After the propensity-score matching, the clinical pregnancy rate of women with longer infertility duration were also higher. When the duration of infertility was more than 5 years, the clinical pregnancy rate of women younger than 35 years old decreased with the increase of infertility duration (aOR: 0.906, 95%CI: 0.800–0.998, p = 0.043).

Conclusions

The clinical pregnancy rate and live birth rate of IUI in young women (< 35 years old) who have been infertile for more than 5 years significantly decrease with the prolongation of infertility time. Therefore, for young women who have been infertile for more than 5 years, IUI may not be the best choice.
Role of beta-(1→3)(1→6)-D-glucan derived from yeast on natural killer (NK) cells and breast cancer cell lines in 2D and 3D cultures
Authors: Boulifa Abdelhadi , Raftery Martin J. , Franzén Alexander Sebastian , Radecke Clarissa , Stintzing Sebastian , Blohmer Jens-Uwe , Pecher Gabriele
Published: March 2024

Background

Beta-(1,3)(1,6)-D-glucan is a complex polysaccharide, which is found in the cell wall of various fungi, yeasts, bacteria, algae, barley, and oats and has immunomodulatory, anticancer and antiviral effects. In the present study, we investigated the effect of beta-(1,3)(1,6)-D-glucan derived from yeast on the proliferation of primary NK cells and breast cancer cell lines in 2D and 3D models, and on the cytotoxicity of primary NK cells against breast cancer cell lines in 2D and 3D models.

Methods

In this study, we investigated the effects of different concentrations of yeast-derived beta-(1→3)(1→6)-D-glucan on the proliferation and cytotoxicity of human NK cells and breast cancer cell lines in 2D and 3D models using the XTT cell proliferation assay and the CellTiter-Glo® 2.0 assay to determine the cytotoxicity of human NK cells on breast cancer cell lines in 2D and 3D models.

Results

We found that the co-incubation of NK cells with beta-glucan in the absence of IL2 at 48 h significantly increased the proliferation of NK cells, whereas the co-incubation of NK cells with beta-glucan in the presence of IL2 (70 U/ml) increased the proliferation of NK cells but not significantly. Moreover, beta-glucan significantly inhibited the proliferation of breast cancer cell lines in 2D model and induced a weak, non-significant growth inhibitory effect on breast cancer multicellular tumor spheroids (3D). In addition, the cytotoxicity of NK cells against breast cancer cell lines was examined in 2D and 3D models, and beta-glucan significantly increased the cytotoxicity of NK cells against MCF-7 (in 2D).

Conclusions

Yeast derived beta-(1,3)(1,6)-D-glucan could contribute to the treatment of cancer by enhancing NK cell immune response as well as contributing to inhibition of breast cancer cell growth.
Adult head and neck rhabdomyosarcoma: radiotherapy- based treatment, outcomes, and predictors of survival
Authors: Zhao Dan , Zhou Fang , Liu Weixin , Huang Zhou , Xu Xiaolong , Zheng Baomin , Liu Changqing , Bai Chujie , Liu Jiayong , Sun Yan , Wang Weihu , Xiao Shaowen
Published: March 2024

Background

Adult head and neck rhabdomyosarcoma (HNRMS) is an exceptionally rare malignancy, and there is a paucity of data and research dedicated to understanding its characteristics and management in adult populations. This study aimed to assess the outcomes and identify survival predictors in adult HNRMS.

Methods

We retrospectively evaluated 42 adult patients (> 16 years) with HNRMS who received radiotherapy (RT)-based treatment at our institute between 2008 and 2022. We analysed the clinical characteristics and prognosis of these patients, including the locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS), using the Kaplan–Meier method. The chi-square and Fisher’s exact tests were used to analyse differences between groups for dichotomous and categorical variables, respectively. Survival rates were calculated using the Kaplan–Meier method. Prognostic variables were assessed through univariate Cox analyses.

Results

The median patient age was 28 years (range, 16–82 years). Alveolar RMS was the most common histological type, observed in 21 patients (50.0%), followed by embryonal in 16 patients (38.1%). The anatomic sites of origin were orbital in one (2.4%), parameningeal in 26 (61.9%), and non-orbital/non-parameningeal in 15 (35.7%) patients. Nineteen patients (45.2%) had regional lymph node metastasis, and five patients (11.9%) presented with distant metastatic disease. Distant metastasis (n = 17) was the primary cause of treatment failure. At a median follow-up of 47.0 months, the 5-year LRFS, PFS, and OS rates were 69.0%, 39.7%, and 41.0%, respectively. Univariate analysis revealed that tumour size, lymph node involvement, and the local treatment pattern (surgery and RT vs. RT alone) were significant predictors of survival.

Conclusions

The main failure pattern in patients with HNRMS receiving RT-based treatment was distant metastasis. Tumour size > 5 cm and lymph node involvement were predictors of worse LRFS. Multimodality local treatment, combining surgery and RT, is effective and provides survival benefits.
Is low-dose computed tomography for lung cancer screening conveniently accessible in China? A spatial analysis based on cross-sectional survey
Authors: Pan Jay , Wang Jianjian , Tao Wenjuan , Wang Chaohui , Lin Xiaojun , Wang Xiuli , Li Ruicen
Published: March 2024

Background

Regular Low-Dose Computed Tomography (LDCT) for lung cancer high-risk population has been proved to improve health outcomes and relieve disease burden efficiently for both individual and society. With geographical impedance becoming the major barrier preventing patients from getting timely healthcare service, this study incorporated health seeking behavior in estimating spatial accessibility of relative scarce LDCT resource in China, thus to provide real-world evidence for future government investment and policy making.

Methods

Taking Sichuan Province in southwest China as the study area, a cross-sectional survey was first carried out to collect actual practice and preferences for seeking LDCT services. Using Computed Tomography (CT) registration data reported by owner institutions representing LDCT services capacity, and grided town-level high-risk population as demand, the Nearest Neighbor Method was then utilized to calculate spatial accessibility of LDCT services.

Results

A total of 2,529 valid questionnaires were collected, with only 34.72% of the high-risk populations (746 individuals) followed the recommended annual screening. Participants preferred to travel to municipal-level and above institutions within 60 min for LDCT services. Currently, every thousand high-risk populations own 0.0845 CT scanners in Sichuan Province, with 96.95% able to access LDCT within 60 min and over half within 15 min. Urban areas generally showed better accessibility than rural areas, and the more developed eastern regions were better than the western regions with ethnic minority clusters.

Conclusions

Spatial access to LDCT services is generally convenient in Sichuan Province, but disparity exists between different regions and population groups. Improving LDCT capacity in county-level hospitals as well as promoting health education and policy guidance to the public can optimize efficiency of existing CT resources. Implementing mobile CT services and improving rural public transportation may alleviate emerging disparities in accessing early lung cancer detection.
Secretion of glucagon, GLP-1 and GIP may be affected by circadian rhythm in healthy males
Authors: Zilstorff Dorte B. , Richter Michael M. , Hannibal Jens , Jørgensen Henrik L. , Sennels Henriette P. , Wewer Albrechtsen Nicolai J.
Published: March 2024

Background

Glucagon is secreted from pancreatic alpha cells in response to low blood glucose and increases hepatic glucose production. Furthermore, glucagon enhances hepatic protein and lipid metabolism during a mixed meal. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from gut endocrine cells during meals and control glucose homeostasis by potentiating insulin secretion and inhibiting food intake.

Both glucose homeostasis and food intake have been reported to be affected by circadian rhythms and vice versa. In this study, we investigated whether the secretion of glucagon, GLP-1 and GIP was affected by circadian rhythms.

Methods

A total of 24 healthy men with regular sleep schedules were examined for 24 h at the hospital ward with 15 h of wakefulness and 9 h of sleep. Food intake was standardized, and blood samples were obtained every third hour. Plasma concentrations of glucagon, GLP-1 and GIP were measured, and data were analyzed by rhythmometric statistical methods. Available data on plasma glucose and plasma C-peptide were also included.

Results

Plasma concentrations of glucagon, GLP-1, GIP, C-peptide and glucose fluctuated with a diurnal 24-h rhythm, with the highest levels during the day and the lowest levels during the night: glucagon (p < 0.0001, peak time 18:26 h), GLP-1 (p < 0.0001, peak time 17:28 h), GIP (p < 0.0001, peak time 18:01 h), C-peptide (p < 0.0001, peak time 17.59 h), and glucose (p < 0.0001, peak time 23:26 h). As expected, we found significant correlations between plasma concentrations of C-peptide and GLP-1 and GIP but did not find correlations between glucose concentrations and concentrations of glucagon, GLP-1 and GIP.

Conclusions

Our results demonstrate that under meal conditions that are similar to that of many free-living individuals, plasma concentrations of glucagon, GLP-1 and GIP were observed to be higher during daytime and evening than overnight. These findings underpin disturbed circadian rhythm as a potential risk factor for diabetes and obesity.

Trial registration

ClinicalTrials.gov Identifier: NCT06166368. Registered 12 December 2023.
Plasma adiponectin/leptin ratio associates with subcutaneous abdominal and omental adipose tissue characteristics in women
Authors: Tremblay Eve-Julie , Tchernof André , Pelletier Mélissa , Joanisse Denis R. , Mauriège Pascale
Published: March 2024

Background

A better understanding of adipose tissue (AT) dysfunction, which includes morphological and functional changes such as adipocyte hypertrophy as well as impaired adipogenesis, lipid storage/mobilization, endocrine and inflammatory responses, is needed in the context of obesity. One dimension of AT dysfunction, secretory adiposopathy, often assessed as a low plasma adiponectin (A)/leptin (L) ratio, is commonly observed in obesity. The aim of this study was to examine markers of AT development and metabolism in 67 women of varying age and adiposity (age: 40-62 years; body mass index, BMI: 17-41 kg/m2) according to levels of adiponectinemia, leptinemia or the plasma A/L ratio.

Methods

Body composition, regional AT distribution and circulating adipokines were determined. Lipolysis was measured from glycerol release in subcutaneous abdominal (SCABD) and omental (OME) adipocytes under basal, isoproterenol-, forskolin (FSK)- and dibutyryl-cyclic AMP (DcAMP)-stimulated conditions. Adipogenesis (C/EBP-α/β/δ, PPAR-γ2 and SREBP-1c) and lipid metabolism (β2-ARs, HSL, FABP4, LPL and GLUT4) gene expression (RT-qPCR) was assessed in both fat depots. Participants in the upper versus lower tertile of adiponectin, leptin or the A/L ratio were compared.

Results

Basal lipolysis was similar between groups. Women with a low plasma A/L ratio were characterized by higher adiposity and larger SCABD and OME adipocytes (p<0.01) compared to those with a high ratio. In OME adipocytes, women in the low adiponectinemia tertile showed higher isoproterenol-stimulated lipolysis (0.01<p<0.05), while those in the high leptinemia tertile displayed increased lipolytic response to this agent (p<0.05). However, lipolysis stimulated by isoproterenol was enhanced in both compartments (0.01<p<0.05) in women with a low plasma A/L ratio. AT abundance of selected transcripts related to adipogenesis or lipid metabolism did not differ between women with or without secretory adiposopathy, except for lower GLUT4 mRNA levels in OME fat.

Conclusions

Secretory adiposopathy assessed as the plasma A/L ratio, more so than adiponectin or leptin levels alone, discriminates low and elevated lipolysis in OME and SCABD adipocytes despite similar AT expression of selected genes involved in lipid metabolism.
Effect of thermocycling on the mechanical properties of permanent composite-based CAD-CAM restorative materials produced by additive and subtractive manufacturing techniques
Authors: Temizci Tuğba , Bozoğulları Hatice Nalan
Published: March 2024

Background

The aim of the study was to determine and compare the biaxial flexural strength (BFS) and Vickers hardness (VHN) of additive and subtractive manufactured permanent composite-based restorative materials, before and after thermal aging.

Methods

A total of 200 specimens were prepared; 100 disc-shaped specimens (diameter 13 × 1.2 mm) for the BFS test and 100 square specimens (14 × 14 × 2 mm) for the VHN test. The specimens were made from various materials: two subtractive composite-based blocks (Cerasmart 270 [CS], Vita Enamic [VE]), two additive composite-based resins used for two different vat polymerization methods (digital light processing [DLP]; Saremco Print Crowntec [SC] and stereolithography [SLA]; Formlabs Permanent Crown Resin [FP]), and one feldspathic glass-matrix ceramic block (Vita Mark II [VM]) as the control group. Specimens of each material were divided into two subgroups: thermal cycled or non-thermal cycled (n = 10). BFS and VHN tests were performed on all groups. Data were analyzed with two-way ANOVA and post hoc Tukey test (α = 0.05).

Results

The type of restorative material used for the specimen had a statistically significant influence on both BFS and VHN values. However, thermal cycling did not affect the BFS and VHN values. After thermal cycling, the results of the BFS test were ranked from best to worst as follows: CS, FP, SC, VE, then VM. For the VHN values, the order from best to worst was as follows: VM, VE, CS, FP, then SC.

Conclusions

3D printed and milled composite groups showed higher BFS than feldspathic ceramics. When the VHN results were examined, it was seen that the 3D resin groups had the lowest VHN values. Furthermore, it was observed that the thermal cycle had no effect on BFS or VHN.
The effect of three additives on properties of mineral trioxide aggregate cements: a systematic review and meta-analysis of in vitro studies
Authors: Bolhari Behnam , Noori Faranak , Assadian Hadi , Raee Amir , Ghabraei Sholeh , Shamshiri Ahmad-Reza , Heboyan Artak
Published: March 2024

Background

Several efforts have been made to improve mechanical and biological properties of calcium silicate-based cements through changes in chemical composition of the materials. This study aimed to investigate the physical (including setting time and compressive strength) and chemical (including calcium ion release, pH level) properties as well as changes in cytotoxicity of mineral trioxide aggregate (MTA) after the addition of 3 substances including CaCl2, Na2HPO4, and propylene glycol (PG).

Methods

The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Electronic searches were performed on PubMed, Embase, and Scopus databases, spanning from 1993 to October 2023 in addition to manual searches. Relevant laboratory studies were included. The quality of the included studies was assessed using modified ARRIVE criteria. Meta-analyses were performed by RevMan statistical software.

Results

From the total of 267 studies, 24 articles were included in this review. The results of the meta-analysis indicated that addition of PG increased final setting time and Ca2+ ion release. Addition of Na2HPO4 did not change pH and cytotoxicity but reduced the final setting time. Incorporation of 5% CaCl2 reduced the setting time but did not alter the cytotoxicity of the cement. However, addition of 10% CaCl2 reduced cell viability, setting time, and compressive strength.

Conclusion

Inclusion of 2.5% wt. Na2HPO4 and 5% CaCl2 in MTA can be advisable for enhancing the physical, chemical, and cytotoxic characteristics of the admixture. Conversely, caution is advised against incorporating elevated concentrations of PG due to its retarding effect.

Trial registration

PROSPERO registration number: CRD42021253707.
Development and validation of an objective virtual reality tool for assessing technical aptitude among potential candidates for surgical training
Authors: Gazit Noa , Ben-Gal Gilad , Eliashar Ron
Published: March 2024

Background

Good technical skills are crucial for surgeons. Yet although surgical training programs strive to assess technical aptitude when selecting surgical residents, valid assessments of such aptitude are still lacking. Surgical simulators have been proposed as a potentially effective tool for this purpose. The current study aims to develop a technical aptitude test using a virtual reality surgical simulator, and to validate its use for the selection of surgical residents.

Methods

The study had three phases. In Phase 1, we developed an initial version of the technical aptitude test using the Lap-X-VR laparoscopic simulator. In Phases 2 and 3 we refined the test and collected empirical data to evaluate four main sources of validity evidence (content, response process, internal structure, and relationships with other variables), and to evaluate the feasibility and acceptability of the test. Specifically, Phase 2 comprised a review of the test by 30 senior surgeons, and in Phase 3 a revised version of the test was administered to 152 interns to determine its psychometric properties.

Results

Both the surgeons and interns rated the test as highly relevant for selecting surgical residents. Analyses of the data obtained from the trial administration of the test supported the appropriateness of the score calculation process and showed good psychometric properties, including reliability (α = 0.83) and task discrimination (mean discrimination = 0.5, SD = 0.1). The correlations between test scores and background variables revealed significant correlations with gender, surgical simulator experience, and video game experience (ps < 0.001). These variables, however, explained together only 10% of the variance in test scores.

Conclusions

We describe the systematic development of an innovative virtual reality test for assessing technical aptitude in candidates for surgical training, and present evidence for its validity, feasibility and acceptability. Further validation is required to support the application of the test for selection, as well as to discern the impact of gender, surgical simulator experience, and video game experience on the fairness of test results. However, the test appears to be a promising tool that may help training programs assess the suitability of candidates for surgical training.
Challenges to the delivery and utilisation of child healthcare services: a qualitative study of the experiences of nurses and caregivers in a rural district in Ghana
Authors: Nyande Felix Kwasi , Ricks Esmeralda , Williams Margaret , Jardien-Baboo Sihaam
Published: March 2024

Background

Sub-Saharan Africa has one of the poorest child health outcomes in the world. Children born in this region face significant health challenges that jeopardise their proper growth and development. Even though the utilisation of child healthcare services safeguards the health of children, the challenges encountered by nurses in the delivery of services, and caregivers in the utilisation of these services, especially in rural areas, have contributed to poor child health outcomes in this region.

Aim

This study explored the experiences of nurses and caregivers in respect of the nursing human resource challenges to the delivery and utilisation of child healthcare services in a rural district in Ghana.

Methods

Individual qualitative interviews were conducted with ten nurses, who rendered child healthcare services; nine caregivers, who regularly utilised the available child healthcare services; and seven caregivers, who were not regular users of these services. These participants were purposively selected for the study. Data were collected using individual semi-structured interview guides and analysed qualitatively using content analysis. Themes and sub-themes were generated during the data analysis. The Ghana Health Service Research Ethics Review Committee and the Nelson Mandela University’s Research Ethics Committee approved the study protocol prior to data collection.

Results

Three main themes emerged from the data analysis. Theme One focused on the shortage of nurses, which affected the quality and availability of child healthcare services. Theme Two focused on inexperienced nurses, who struggled to cope with the demands related to the delivery of child healthcare services. Theme Three focused on the undesirable attitude displayed by nurses, which discouraged caregivers from utilising child healthcare services.

Conclusion

Nurses contribute significantly to the delivery of child healthcare services; hence, the inadequacies amongst nurses, in terms of staff numbers and nursing expertise, affect the quality and availability of child healthcare services. Also, caregivers’ perceptions of the quality of child healthcare services are based on the treatment they receive at the hands of nurses and other healthcare workers. In this respect, the bad attitude of nurses may disincentivise caregivers in terms of their utilisation of these services, as and when needed. There is an urgent need to comprehensively address these challenges to improve child healthcare outcomes in rural areas in Ghana. Relevant authorities should decentralise training workshops for nurses in rural areas to update their skills. Additionally, health facilities should institute proper orientation and mentoring systems to assist newly recruited nurses to acquire the requisite competences for the delivery of quality family-centred care child healthcare services.
Compassionate care during the COVID-19 pandemic
Authors: Su Jing Jing , Bayuo Jonathan , Lin Rose S.Y. , Wong Arkers Kwan Ching , Abu-Odah Hammoda , He Qijun , Batalik Ladislav
Published: March 2024

Background

There was a substantial documented call for healthcare professionals to provide compassionate care during the COVID-19 pandemic and significant criticism voiced when it was lacking. This study aimed to explore perspectives on compassionate care among healthcare professionals providing care during the COVID-19 pandemic. The study focuses on healthcare professionals who participated in a wide range of COVID-19 measures, including testing, quarantine, diagnosis, and care provision (patients with COVID-19 or patients with other illnesses and comorbid with COVID-19).

Methods

A qualitative design with an interpretative phenomenological analysis approach was used. Twenty frontline healthcare professionals (15 nurses and five physicians) who had worked in COVID-19 facilities in China were interviewed individually.

Results

Participants stated that a commitment to ‘offering oneself’ and ‘balancing the advantages/disadvantages’ in providing care during the pandemic were key to alleviate population-level suffering. On a personal level, they described a desire for obtaining ‘mutual support’ and improving ‘professional competencies’ to safeguard their physical and mental well-being. Two professional competencies were notable: coping with grief and implementing infection control across the organization. Additionally, they emphasized the importance of receiving support from the health care organization, the public, and leaders in creating an ‘environment conducive to fostering compassionate care.’

Conclusion

Healthcare professionals recognized the centrality of compassionate care during the pandemic which entailed a commitment to offering themselves, the balancing of advantages and disadvantages in order to find the best solution, as well as the need to safeguard themselves using professional competencies. Such findings can enrich the contemporary understanding of compassion, including when it is lacking. Support from the healthcare organization, the public, and leadership were crucial in fostering compassionate care in healthcare professionals during the pandemic and in moving the field forward in the future.
Experiences with telemedicine-based follow-up of chronic conditions: the views of patients and health personnel enrolled in a pragmatic randomized controlled trial
Authors: Sten-Gahmberg Susanna , Pedersen Kine , Harsheim Ingrid Gaarder , Løyland Hanna Isabel , Abelsen Birgit
Published: March 2024

Background

Telemedicine is often promoted as a possible solution to some of the challenges healthcare systems in many countries face, and an increasing number of studies evaluate the clinical effects. So far, the studies show varying results. Less attention has been paid to systemic factors, such as the context, implementation, and mechanisms of these interventions.

Methods

This study evaluates the experiences of patients and health personnel enrolled in a pragmatic randomized controlled trial comparing telemedicine-based follow-up of chronic conditions with usual care. Patients in the intervention group received an individual treatment plan together with computer tablets and home telemonitoring devices to report point-of-care measurements, e.g., blood pressure, blood glucose or oxygen saturation, and to respond to health related questions reported to a follow-up service. In response to abnormal measurement results, a follow-up service nurse would contact the patient and consider relevant actions. We conducted 49 interviews with patients and 77 interviews with health personnel and managers at the local centers. The interview data were analyzed using thematic analysis and based on recommendations for conducting process evaluation, considering three core aspects within the process of delivering a complex intervention: (1) context, (2) implementation, and (3) mechanisms of impact.

Results

Patients were mainly satisfied with the telemedicine-based service, and experienced increased safety and understanding of their symptoms and illness. Implementation of the service does, however, require dedicated resources over time. Slow adjustment of other healthcare providers may have contributed to the absence of reductions in the use of specialized healthcare and general practitioner (GP) services. An evident advantage of the service is its flexibility, yet this may also challenge cost-efficiency of the intervention.

Conclusions

The implementation of a telemedicine-based service in primary healthcare is a complex process that is sensitive to contextual factors and that requires time and dedicated resources to ensure successful implementation.

Trial registration

The trial was registered in www.clinicaltrials.gov (NCT04142710). Study start: 2019-02-09, Study completion: 2021-06-30, Study type: Interventional, Intervention/treatment: Telemedicine tablet and tools to perform measurements. Informed and documented consent was obtained from all subjects and next of kin participating in the study.
Modeling antibody drug conjugate potential using a granzyme B antibody fusion protein
Authors: Anderson Trevor S. , McCormick Amanda L. , Smith Savanna L. , Lowe Devin B.
Published: March 2024

Background

Antibody drug conjugates (ADCs) constitute a promising class of targeted anti-tumor therapeutics that harness the selectivity of monoclonal antibodies with the potency of cytotoxic drugs. ADC development is best suited to initially screening antibody candidates for desired properties that potentiate target cell cytotoxicity. However, validating and producing an optimally designed ADC requires expertise and resources not readily available to certain laboratories.

Results

In this study, we propose a novel approach to help streamline the identification of potential ADC candidates by utilizing a granzyme B (GrB)-based antibody fusion protein (AFP) for preliminary screening. GrB is a non-immunogenic serine protease expressed by immune effector cells such as CD8 + T cells that induces apoptotic activity and can be leveraged for targeted cell killing.

Conclusions

Our innovative model allows critical antibody parameters (including target cell binding, internalization, and cytotoxic potential) to be more reliably evaluated in vitro through the creation of an ADC surrogate. Successful incorporation of this AFP could also significantly expand and enhance ADC development pre-clinically, ultimately leading to the accelerated translation of ADC therapies for patients.
Polygenic risk score-based phenome-wide association study of head and neck cancer across two large biobanks
Authors: Lee Young Chan , Jung Sang-Hyuk , Shivakumar Manu , Cha Soojin , Park Woong-Yang , Won Hong-Hee , Eun Young-Gyu , Biobank Penn Medicine , Kim Dokyoon
Published: March 2024

Background

Numerous observational studies have highlighted associations of genetic predisposition of head and neck squamous cell carcinoma (HNSCC) with diverse risk factors, but these findings are constrained by design limitations of observational studies. In this study, we utilized a phenome-wide association study (PheWAS) approach, incorporating a polygenic risk score (PRS) derived from a wide array of genomic variants, to systematically investigate phenotypes associated with genetic predisposition to HNSCC. Furthermore, we validated our findings across heterogeneous cohorts, enhancing the robustness and generalizability of our results.

Methods

We derived PRSs for HNSCC and its subgroups, oropharyngeal cancer and oral cancer, using large-scale genome-wide association study summary statistics from the Genetic Associations and Mechanisms in Oncology Network. We conducted a comprehensive investigation, leveraging genotyping data and electronic health records from 308,492 individuals in the UK Biobank and 38,401 individuals in the Penn Medicine Biobank (PMBB), and subsequently performed PheWAS to elucidate the associations between PRS and a wide spectrum of phenotypes.

Results

We revealed the HNSCC PRS showed significant association with phenotypes related to tobacco use disorder (OR, 1.06; 95% CI, 1.05–1.08; P = 3.50 × 10−15), alcoholism (OR, 1.06; 95% CI, 1.04–1.09; P = 6.14 × 10-9), alcohol-related disorders (OR, 1.08; 95% CI, 1.05–1.11; P = 1.09 × 10−8), emphysema (OR, 1.11; 95% CI, 1.06–1.16; P = 5.48 × 10−6), chronic airway obstruction (OR, 1.05; 95% CI, 1.03–1.07; P = 2.64 × 10−5), and cancer of bronchus (OR, 1.08; 95% CI, 1.04–1.13; P = 4.68 × 10−5). These findings were replicated in the PMBB cohort, and sensitivity analyses, including the exclusion of HNSCC cases and the major histocompatibility complex locus, confirmed the robustness of these associations. Additionally, we identified significant associations between HNSCC PRS and lifestyle factors related to smoking and alcohol consumption.

Conclusions

The study demonstrated the potential of PRS-based PheWAS in revealing associations between genetic risk factors for HNSCC and various phenotypic traits. The findings emphasized the importance of considering genetic susceptibility in understanding HNSCC and highlighted shared genetic bases between HNSCC and other health conditions and lifestyles.
Epidemiology of Plasmodium vivax in Duffy negatives and Duffy positives from community and health centre collections in Ethiopia
Authors: Bradley Lauren , Yewhalaw Delenasaw , Hemming-Schroeder Elizabeth , Jeang Brook , Lee Ming-Chieh , Zemene Endalew , Degefa Teshome , Lo Eugenia , King Christopher , Kazura James , Yan Guiyun
Published: March 2024

Background

Malaria remains a significant cause of morbidity and mortality in Ethiopia with an estimated 3.8 million cases in 2021 and 61% of the population living in areas at risk of malaria transmission. Throughout the country Plasmodium vivax and Plasmodium falciparum are co-endemic, and Duffy expression is highly heterogeneous. The public health significance of Duffy negativity in relation to P. vivax malaria in Ethiopia, however, remains unclear. This study seeks to explore the prevalence and rates of P. vivax malaria infection across Duffy phenotypes in clinical and community settings.

Methods

A total of 9580 and 4667 subjects from community and health facilities from a malaria endemic site and an epidemic-prone site in western Ethiopia were enrolled and examined for P. vivax infection and Duffy expression from February 2018 to April 2021. Association between Duffy expression, P. vivax and P. falciparum infections were examined for samples collected from asymptomatic community volunteers and symptomatic subjects from health centres.

Results

Infection rate of P. vivax among Duffy positives was 2–22 fold higher than Duffy negatives in asymptomatic volunteers from the community. Parasite positivity rate was 10–50 fold higher in Duffy positives than Duffy negatives among samples collected from febrile patients attending health centres and mixed P. vivax and P. falciparum infections were significantly more common than P. vivax mono infections among Duffy negative individuals. Plasmodium vivax parasitaemia measured by 18sRNA parasite gene copy number was similar between Duffy positives and Duffy negatives.

Conclusions

Duffy negativity does not offer complete protection against infection by P. vivax, and cases of P. vivax in Duffy negatives are widespread in Ethiopia, being found in asymptomatic volunteers from communities and in febrile patients from health centres. These findings offer evidence for consideration when developing control and intervention strategies in areas of endemic P. vivax and Duffy heterogeneity.
Insecticide susceptibility status of Anopheles gambiae mosquitoes and the effect of pre-exposure to a piperonyl butoxide (PBO) synergist on resistance to deltamethrin in northern Namibia
Authors: Joseph Rosalia N. , Mwema Tabeth , Eiseb Seth J. , Maliti Deodatus V. , Tambo Munyaradzi , Iitula Iitula , Eloff Lydia , Lukubwe Ophilia , Smith-Gueye Cara , Vajda Élodie A. , Tatarsky Allison , Katokele Stark T. , Uusiku Petrina N. , Walusimbi Dennis , Ogoma Sheila B. , Mumbengegwi Davis R. , Lobo Neil F.
Published: March 2024

Background

Pyrethroid-based indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) have been employed as key vector control measures against malaria in Namibia. However, pyrethroid resistance in Anopheles mosquitoes may compromise the efficacy of these interventions. To address this challenge, the World Health Organization (WHO) recommends the use of piperonyl butoxide (PBO) LLINs in areas where pyrethroid resistance is confirmed to be mediated by mixed function oxidase (MFO).

Methods

This study assessed the susceptibility of Anopheles gambiae sensu lato (s.l.) mosquitoes to WHO tube bioassays with 4% DDT and 0.05% deltamethrin insecticides. Additionally, the study explored the effect of piperonyl butoxide (PBO) synergist by sequentially exposing mosquitoes to deltamethrin (0.05%) alone, PBO (4%) + deltamethrin (0.05%), and PBO alone. The Anopheles mosquitoes were further identified morphologically and molecularly.

Results

The findings revealed that An. gambiae sensu stricto (s.s.) (62%) was more prevalent than Anopheles arabiensis (38%). The WHO tube bioassays confirmed resistance to deltamethrin 0.05% in the Oshikoto, Kunene, and Kavango West regions, with mortality rates of 79, 86, and 67%, respectively. In contrast, An. arabiensis displayed resistance to deltamethrin 0.05% in Oshikoto (82% mortality) and reduced susceptibility in Kavango West (96% mortality). Notably, there was reduced susceptibility to DDT 4% in both An. gambiae s.s. and An. arabiensis from the Kavango West region. Subsequently, a subsample from PBO synergist assays in 2020 demonstrated a high proportion of An. arabiensis in Oshana (84.4%) and Oshikoto (73.6%), and 0.42% of Anopheles quadriannulatus in Oshana. Non-amplifiers were also present (15.2% in Oshana; 26.4% in Oshikoto). Deltamethrin resistance with less than 95% mortality, was consistently observed in An. gambiae s.l. populations across all sites in both 2020 and 2021. Following pre-exposure to the PBO synergist, susceptibility to deltamethrin was fully restored with 100.0% mortality at all sites in 2020 and 2021.

Conclusions

Pyrethroid resistance has been identified in An. gambiae s.s. and An. arabiensis in the Kavango West, Kunene, and Oshikoto regions, indicating potential challenges for pyrethroid-based IRS and LLINs. Consequently, the data highlights the promise of pyrethroid-PBO LLINs in addressing resistance issues in the region.
Multiple high-risk HPV infections probably associated with a higher risk of low-grade cytological abnormalities but not with high-grade intraepithelial lesions of the cervix
Authors: Tong Tong , Su Di , Yang Qi , Yang Kun , Liu Yuqi , Wang Qun , Tian Tian
Published: March 2024

Background

For women diagnosed with HR-HPV DNA positivity in community hospitals, the necessity of investigating the potential presence of multiple HR-HPV infections upon referral to tertiary medical institutions remains unclear.

Methods

In our cohort, women tested positive for HR-HPV DNA during examinations in community hospitals, were subsequently referred to tertiary medical facilities, reevaluated HR-HPV genotype and categorized based on cytological and histopathological results. The risk of cytologic/histopathology abnormalities and ≧ high grade squamous intraepithelial lesion(HSIL) or Cervical Intraepithelial Neoplasia (CIN) 2 associated with individual genotypes and related multiple HPV infections are calculated.

Results

A total of 1677 women aged between 21 and 77 were finally included in the present study. The cytology group included 1202 women and the histopathological group included 475 women with at least one HR-HPV infection of any genotype. We only observed a higher risk of low grade cytological abnormalities in women with multiple infections than those in corresponding single infections (for all population with an OR of 1.85[1.39–2.46]; p < 0.05). However, this phenomenon was not observed in histopathology abnormalities (CIN1). The risk of developing of ≥ HSIL/CIN2 in women who were infected with multiple HR-HPV also showed a similar profile to those with a single HR-HPV genotype.

Conclusion

Multiple HR-HPV infections is only associated with a higher associated risk of low grade cytological abnormalities. There is no evidence of clinical benefit to identify the possible presence of multiple HR-HPV infection frequently in a short period of time for women with HR-HPV-DNA positive.
CLPs-miR-103a-2-5p inhibits proliferation and promotes cell apoptosis in AML cells by targeting LILRB3 and Nrf2/HO-1 axis, regulating CD8 + T cell response
Authors: Cen Qingyan , Chen Jianyu , Guo Jiaxin , Chen Mu , Wang Hao , Wu Suwan , Zhang Honghao , Xie Xiaoling , Li Yuhua
Published: March 2024

Background

LILRB3, a member of the leukocyte immunoglobulin-like receptor B (LILRB) family, has immunosuppressive functions and directly regulates cancer development, which indicates that LILRB3 is an attractive target for cancer diagnosis and therapy. Novel therapeutic treatments for acute myeloid leukemia (AML) are urgent and important, and RNA therapeutics including microRNAs (miRNAs) could be an effective option. Here, we investigate the role of dysregulated miRNA targeting LILRB3 in the AML microenvironment.

Methods

Potential miRNAs binding to the 3ʹ-untranslated region (3ʹ-UTR) of the LILRB3 mRNA were predicted by bioinformatics websites. Then, we screened miRNAs targeting LILRB3 by quantitative real-time PCR, and the dual luciferase reporter assay. The expression of LILRB3 and microRNA (miR)-103a-2-5p in AML were determined and then their interactions were also analyzed. In vitro, the effects of miR-103a-2-5p were determined by CCK8, colony formation assay, and transwell assay, while cell apoptosis and cell cycle were analyzed by flow cytometry. Cationic liposomes (CLPs) were used for the delivery of miR-103a-2-5p in the AML mouse model, which was to validate the potential roles of miR-103a-2-5p in vivo.

Results

LILRB3 was upregulated in AML cells while miR-103a-2-5p was dramatically downregulated. Thus, a negative correlation was found between them. MiR-103a-2-5p directly targeted LILRB3 in AML cells. Overexpressed miR-103a-2-5p significantly suppressed the mRNA and protein levels of LILRB3, thereby inhibiting AML cell growth and reducing CD8 + T cell apoptosis. In addition, overexpressed miR-103a-2-5p reduced both the relative expression of Nrf2/HO-1 pathway-related proteins and the ratio of GSH/ROS, leading to the excessive intracellular ROS that may promote AML cell apoptosis. In the mouse model, the delivery of miR-103a-2-5p through CLPs could inhibit tumor growth.

Conclusions

MiR-103a-2-5p serves as a tumor suppressor that could inhibit AML cell proliferation and promote their apoptosis by downregulating LILRB3 expression, suppressing the Nrf2/HO-1 axis, and reducing the ratio of GSH/ROS. Besides, our findings indicate that miR-103a-2-5p may enhance the CD8 + T cell response by inhibiting LILRB3 expression. Therefore, the delivery of miR-103a-2-5p through CLPs could be useful for the treatment of AML.
Construction and applications of the EOMA spheroid model of Kaposiform hemangioendothelioma
Authors: Li Yanan , Zhu Xinglong , Li Li , Bao Chunjuan , Liu Qin , zhang Ning , He Ziyan , Ji Yi , Bao Ji
Published: March 2024

Background

Kaposiform hemangioendothelioma (KHE) is a rare intermediate vascular tumor with unclear pathogenesis. Recently, three dimensional (3D) cell spheroids and organoids have played an indispensable role in the study of many diseases, such as infantile hemangioma and non-involuting congenital hemangiomas. However, few research on KHE are based on the 3D model. This study aims to evaluate the 3D superiority, the similarity with KHE and the ability of drug evaluation of EOMA spheroids as an in vitro 3D KHE model.

Results

After two days, relatively uniform morphology and high viability of EOMA spheroids were generated by the rotating cell culture system (RCCS). Through transcriptome analysis, compared with 2D EOMA cells, focal adhesion-related genes such as Itgb4, Flt1, VEGFC, TNXB, LAMA3, VWF, and VEGFD were upregulated in EOMA spheroids. Meanwhile, the EOMA spheroids injected into the subcutaneous showed more obvious KMP than 2D EOMA cells. Furthermore, EOMA spheroids possessed the similar characteristics to the KHE tissues and subcutaneous tumors, such as diagnostic markers (CD31 and LYVE-1), cell proliferation (Ki67), hypoxia (HIF-1α) and cell adhesion (E-cadherin and N-cadherin). Based on the EOMA spheroid model, we discovered that sirolimus, the first-line drug for treating KHE, could inhibit EOMA cell proliferation and downregulate the VEGFC expression. Through the extra addition of VEGFC, the effect of sirolimus on EOMA spheroid could be weakened.

Conclusion

With a high degree of similarity of the KHE, 3D EOMA spheroids generated by the RCCS can be used as a in vitro model for basic researches of KHE, generating subcutaneous tumors and drug screening.