bluuebunny/crossref_metadata_2025 huggingface dataset:
The relative age effect on fundamental movement skills in Chinese children aged 3–5 years
Authors: Li Kai , Chen Sitong , Ma Jiani , Martins Clarice , Duncan Michael , Sheng Xinxin , Liu Shijie , Cai Yujun
Published: April 2023

Background

The cut-off date in the education system causes a relative age difference, with developmental advantages for children who are born on the “early side” of the cut-off date and disadvantages for those born later, which is known as the relative age effect (RAE). Very few studies have examined whether there is a RAE on the development of fundamental movement skills (FMSs) in preschool children, and no studies have been conducted in China. The purpose of this study is to identify whether a RAE exists on FMS in Chinese preschool children, comparing RAEs according to gender and age.

Methods

From a total of 378 invited preschool children regularly registered at one Chinese kindergarten, a total of 288 healthy and typically developing preschoolers (4.33 ± 0.84 years-old; 56.6% boys) were included in this study. All children were required to take part in anthropometry and FMS assessments. Analysis of covariance (ANCOVA) was applied to examine the difference in each of the FMS items across quarter categories, year and gender groups, controlling for body mass index (BMI).

Results

For the overall sample, the data show the significant main effects on the quarter of birth factor in locomotor skills (LC; F (3, 265) = 2.811, p = 0.04, ηp2 = 0.031), object control skills (OB; F (3, 265) = 6.319, p = 0.04, ηp2 = 0.031), and total test score (TTS; F (3, 265) = 5.988, p = 0.001, ηp2 = 0.063). There were also significant differences in the age effect on all the domains of FMS (FLC (2, 265) = 100.654, p < 0.001, ηp2 = 0.432; FOB (2, 265) = 108.430, p < 0.001, ηp2 = 0.450; FTTS (2, 265) = 147.234, p < 0.001, ηp2 = 0.526) but a gender effect only in LC (F (1, 265) = 20.858; p < 0.001; ηp2 = 0.073). For gender and quarter of birth groups, RAEs in LC only exists in girls. Moreover, regarding age and quarter of birth factors, RAEs are only found at younger ages.

Conclusions

This study suggests the existence of RAEs in the FMS of Chinese preschool children. Teachers need to be aware of the effect of RAEs on the FMS when approaching development, evaluation, and teaching approaches in preschools.
An intervention to promote positive homeworker health and wellbeing through effective home-working practices: a feasibility and acceptability study
Authors: Keightley Samuel , Duncan Myanna , Gardner Benjamin
Published: April 2023

Background

In the wake of Covid-19, the prevalence of working from home (‘home-working’) is expected to rise. Yet, working from home can have negative health and wellbeing impacts. Interventions are needed to promote effective ways of working that also protect workers’ health and wellbeing. This study explored the feasibility and acceptability of an intervention intended to promote home-working practices that would protect and promote health behaviour and wellbeing.

Methods

An uncontrolled, single-arm mixed-methods trial design was employed. Forty-two normally-office-based UK workers, working from home between January–February 2021 (during the Covid pandemic), consented to receive the intervention. The intervention: a digital document offering evidence-based recommendations for home-working in ways conducive to health behaviour and wellbeing. Feasibility and acceptability were quantitatively indexed by: expressions of interest within 1 week (target threshold ≥ 35); attrition across the one-week study period (threshold ≤ 20%); and the absence of any apparent detriments in self-reported physical activity, sedentary behaviour, snacking, and work-related wellbeing prior to and one week after receiving the intervention. Qualitative think-aloud data, obtained while participants read through the intervention, and analysed using reflexive thematic analysis, explored acceptability. Semi-structured interviews conducted one week after intervention exposure were content-analysed to identify whether and which behaviour changes were adopted.

Results

Two feasibility criteria were met: 85 expressions of interest indicated satisfactory intervention demand, and no detriments were observed in health behaviours or wellbeing. Forty-two participants (i.e., maximum capacity for the study; 26 females, 16 males, aged 22–63) consented to take part. 31% dropped out over the one-week study period leaving a final sample of 29 (18 females, 11 males, aged 22–63), exceeding identified attrition thresholds. Think-aloud data showed that participants concurred with intervention guidance, but felt it lacked novelty and practicality. Follow-up interviews produced 18 (62%) participant reports of intervention adherence, where nine recommendations reportedly prompted behaviour change in at least one participant.

Conclusions

Mixed evidence was found for intervention feasibility and acceptability. Whilst the information was deemed relevant and of value, further development is required to increase its novelty. It may also be more fruitful to provide this information via employers, to encourage and emphasise employer endorsement.
Understanding risk factors for musculoskeletal disorders in Iranian housewives: Development of a comprehensive health promotion behavior model
Authors: Norouzi Samaneh , Tavafian Sedigheh Sadat , Cousins Rosanna , Mokarami Hamidreza
Published: April 2023

Background

Chronic musculoskeletal problems are a major source of disability, reduced productivity and poor quality of life. Prevalence of musculoskeletal disorders among Iranian housewives is particularly high. Understanding how housework causes the injuries, mobility restrictions and pain associated with musculoskeletal disorders is vital to developing health promotion behavior models to support intervention. The aim of this qualitative study was to explore the experiences of housewives with musculoskeletal disorders and, according to the risk factors identified, to develop a comprehensive behavior change framework to facilitate implementing a musculoskeletal health-promoting training intervention for women.

Methods

Twenty-four in-depth interviews were conducted with Iranian housewives aged 20–65 years experiencing musculoskeletal pain over a 13-month period from September 2020 to October 2021. The conventional content analysis approach was used to interrogate the data. The transcript of each interview was considered a unit of analysis, and data analysis was performed using MAXQDA2018 software.

Results

The analysis of the interview data provided 1432 meaning units. From these codes, a conceptual framework was developed. This comprehensive model is comprised of 24 subcategories, eight categories and three themes: Individual and social predictors of MSDs and their control, Risk factors for MSDs, and Prevention and treatment of MSDs. Altogether the developed conceptual framework specified the multiple risk factors for MSDs in housewives. The findings were aligned to various health promotion models, and it was seen that ecological models, especially the Theory of Triadic Influence, can be very helpful as a supportive roadmap to implementing multilateral interventions to improve the quality of life of housewives.

Conclusions

This study developed an evidence based comprehensive model that identifies the individual, psychosocial, and cultural factors that influence the status of MSDs in women’s domestic work to support the development and implementation of effective ergonomic interventions to manage potentials for MSDs.
Low human beta-defensin-2 levels in the sputum of COPD patients are associated with the risk of exacerbations
Authors: Feng Shengchuan , Yang Yuqiong , Wang Fengyan , Shi Weijuan , Xu Jiaxuan , Tang Guoyan , Xie Jiaxing , Zhong Nanshan , Liang Zhenyu , Chen Rongchang
Published: April 2023

Rationale

Chronic obstructive pulmonary disease (COPD) is a complicated chronic inflammatory disease. It is important to investigate the characteristics of acute exacerbation of COPD to develop new therapeutic strategies.

Objective

This study aimed to determine the relationship between the human beta-defensin-2 (hBD-2) levels and aggravation of COPD.

Methods

We detected the sputum hBD-2 level of 254 patients from Guangzhou, China, for 2 years. The study participants were categorized into the COPD group (n = 203, GOLD 0–4) and the control group (n = 51, 40–79 years old). At baseline, 12th month, and 24th month, we detected the sputum hBD-2 level and levels of cytokines, such as CXCL10, CXCL11, and IFN.

Results

At baseline, there were no significant differences in the sputum and serum hBD-2 levels between the patients and the controls. However, the sputum hBD-2 levels of patients who had at least one symptom aggravation over the next 2 years were significantly lower than those of patients without any exacerbations (1130.9 ± 858.4 pg/mL vs. 2103.7 ± 1294.2 pg/mL, respectively; p = 0.001). Nevertheless, there were no statistically significant differences in the sputum hBD-2 levels between patients (no aggravation history) and controls (2084.9 ± 1317.6 pg/mL vs. 2152.5 ± 1251.6 pg/mL, respectively; p = 0.626). We used a logistic regression model to assess the relationship between aggravation and sputum hBD-2 levels. Interestingly, we found that low hBD-2 level (< 1000 pg/mL) was significantly associated with exacerbations. Specifically, patients with low hBD-2 levels were more likely to experience exacerbations in the next 12 months (0.333 vs. 0.117; p = 0.001). Moreover, we compared the hBD-2 levels between controls and patients with GOLD 3–4 and found that participants with bacteria (+) and/or viruses (+) had an association between hBD-2 level and disease severity (p = 0.02).

Conclusion

Patients at risk of exacerbations are more likely to have lower sputum hBD-2 levels. These results have important implications for future therapies for COPD.
Spanish menstrual literacy and experiences of menstruation
Authors: Sánchez López Sara , Barrington Dani Jennifer , Poveda Bautista Rocio , Moll López Santiago
Published: April 2023

There is growing recognition of the important role menstrual health plays in achieving health, education, and gender equity. Yet, stigmatisation and taboo remain present and negative emotions like fear and shame dominate the narrative when speaking about periods. This paper analyses how formal and informal menstrual education is received in Spain, to understand the role of menstrual health literacy in the way menstruation is experienced, and to identify what information would be useful to integrate into formal menstrual education. An online survey with more than 4000 participants (aged between 14 and 80, both people who will/do/have previously menstruate/d and those who do not menstruate) was conducted. Data was gathered using the digital platform Typeform, descriptive and inferential statistical analyses were performed with SPSS software and qualitative data was thematically analysed using Nvivo. Many participants declared not having received sufficient information on menstruation prior to menarche, particularly about how to physically manage it. Furthermore, negative emotions like shame, worry, and fear were recurrently reported to describe menarche; this has not changed between generations. Interestingly, we saw an increase in stress and sadness with an increase in perceived knowledge of the reproductive role of menstruation. We did observe a reduction in negative emotions when people who menstruate perceived they had sufficient information on how to manage their first bleeding. It is recommended that menstrual education beyond reproductive biology, particularly including how to physically manage periods, is integrated into school curricula. Menstrual education of everyone – including those who do not menstruate—can improve how periods are experienced in Spain.
Decreasing the options’ number in multiple choice questions in the assessment of senior medical students and its effect on exam psychometrics and distractors’ function
Authors: Al-lawama Manar , Kumwenda Ben
Published: April 2023

Background

Studies that have investigated the effect options’ number in MCQ tests used in the assessments of senior medical students are scarce. This study aims to compare exam psychometrics between three- and five-option MCQ tests in final-year assessments.

Methods

A cluster randomized study was applied. Participants were classified into three groups, according to their academic levels. Students in each of those levels were randomized into either the three- or five-option test groups.

Results

Mean time to finish the five-option test was 45 min, versus 32 min for the three-option group. Cronbach’s alpha was 0.89 for the three-option group, versus 0.81 for the five-options, p-value = 0.19. The mean difficulty index for the three-option group was 0.75, compared to 0.73 for the five-option group, p-value = 0.57. The mean discriminating index was 0.53 for the three-option group, and 0.45 for the five-options, p-value = 0.07. The frequency of non-functioning distractors was higher in the five-option test, 111 (56%), versus 39 (39%) in the three-options, with p-value < 0.01.

Conclusions

This study has shown that three-option MCQs are comparable to five-option MCQs, in terms of exam psychometrics. Three-option MCQs are superior to five-option tests regarding distractors’ effectiveness and saving administrative time.
Maternal vaccination against pertussis as part of the national immunization program: a qualitative evaluation among obstetric care providers one year after the implementation in December 2019
Authors: Immink Maarten M. , van Zoonen Kim , Jager Nina M. , Pluijmaekers Anne J.M. , de Melker Hester E. , van der Maas Nicoline A.T. , Bekker Mireille N.
Published: April 2023

Background

Immunization of pregnant women with a tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccine is an effective and safe way to protect infants from pertussis before their primary vaccinations. Vaccine uptake among pregnant women is influenced by their care providers’ attitudes toward maternal vaccination. This qualitative study aimed to evaluate the implementation of the maternal Tdap vaccination under the National Immunization Program of the Netherlands from the perspective of obstetric care providers.

Methods

In this qualitative and explorative study, we conducted in-depth interviews by telephone with obstetric care providers who were selected from a pool of respondents (convenience sampling) to a questionnaire in a previous study. The interviews were based on a semi-structured interview guide that covered three aspects of the implementation strategy: providers’ overall experience with the implementation of maternal Tdap vaccination in the Netherlands; implementation logistics and counseling, and pregnant women referrals to municipal Youth Healthcare Centers. The interviews were recorded, pseudonymized and transcribed verbatim. Transcripts were analyzed according to the Thematic Analysis approach by two researchers independently in two phases of iterative coding, categorizing, reviewing and redefining until ultimately, emergent themes regarding maternal Tdap vaccination implementation were identified.

Results

Interviews with 11 midwives and 5 OB-GYN physicians yielded 5 major themes regarding the Tdap vaccination implementation strategy: challenges throughout the implementation process, views on maternal Tdap vaccination, general versus tailored counseling, provider responsibilities in vaccine promotion, and impact of materials for information delivery. Participants indicated that to improve provider attitudes toward Tdap vaccination, its implementation requires clear and transparent information about what is entailed, i.e., what is expected from obstetric care providers, how they can obtain information, and when their actions must be initiated. Participants demanded involvement throughout the implementation planning process. They preferred tailored communication with pregnant women over a generalized approach.

Conclusion

This study emphasized the importance of involving all relevant healthcare professionals in planning the implementation of maternal Tdap vaccination. Possible barriers perceived by these professionals should be taken into account in order to improve their attitudes toward vaccination, thus to increase uptake among pregnant women.
Estimating the cost of HIV services for key populations provided by the LINKAGES program in Kenya and Malawi
Authors: Opuni Marjorie , Sanchez-Morales Jorge Eduardo , Figueroa Jose Luis , Salas-Ortiz Andrea , Banda Louis Masankha , Olawo Alice , Munthali Spy , Korir Julius , DiCarlo Meghan , Bautista-Arredondo Sergio
Published: April 2023

Background

Data remain scarce on the costs of HIV services for key populations (KPs). The objective of this study was to bridge this gap in the literature by estimating the unit costs of HIV services delivered to KPs in the LINKAGES program in Kenya and Malawi. We estimated the mean total unit costs of seven clinical services: post-exposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), HIV testing services (HTS), antiretroviral therapy (ART), sexually transmitted infection (STI) services, sexual and reproductive health (SRH) services, and management of sexual violence (MSV). These costs take into account the costs of non-clinical services delivered alongside clinical services and the pre-service and above-service program management integral to the LINKAGES program.

Methods

Data were collected at all implementation levels of the LINKAGES program including 30 drop-in-centers (DICs) in Kenya and 15 in Malawi. This study was conducted from the provider’s perspective. We estimated economic costs for FY 2019 and cost estimates include start-up costs. Start-up and capital costs were annualized using a discount rate of 3%. We used a combination of top-down and bottom-up costing approaches. Top-down methods were used to estimate the costs of headquarters, country offices, and implementing partners. Bottom-up micro-costing methods were used to measure the quantities and prices of inputs used to produce services in DICs. Volume-weighted mean unit costs were calculated for each clinical service. Costs are presented in 2019 United States dollars (US$).

Results

The mean total unit costs per service ranged from US$18 (95% CI: 16, 21) for STI services to US$635 (95% CI: 484, 785) for PrEP in Kenya and from US$41 (95% CI: 37, 44) for STI services to US$1,240 (95% CI 1156, 1324) for MSV in Malawi. Clinical costs accounted for between 21 and 59% of total mean unit costs in Kenya, and between 25 and 38% in Malawi. Indirect costs—including start-up activities, the costs of KP interventions implemented alongside clinical services, and program management and data monitoring—made up the remaining costs incurred.

Conclusions

A better understanding of the cost of HIV services is highly relevant for budgeting and planning purposes and for optimizing HIV services. When considering all service delivery costs of a comprehensive HIV service package for KPs, costs of services can be significantly higher than when considering direct clinical service costs alone. These estimates can inform investment cases, strategic plans and other budgeting exercises.
Judicial and legislative practice and related suggestions on off-label drug use in China
Authors: Si Wenjie , Ma Panpan
Published: April 2023

Background

Off-label drug use exists widely in medical practice and is also an area which easily triggers controversy between patients and medical institutions. Previous studies have identified the reasons why off-label drug use long exists. However, there is no multidimensional analysis on real judicial precedents about off-label drug use. This study aimed to investigate the dispute points on off-label drug use based on real cases in China, and proposed suggestions based on newly-leased Physicians Law.

Methods

Our study is a retrospective study with all the 35 judicial precedents on off-label drug use extracted from China Judgments Online from 2014 to 2019. This study mainly used the methods of statistical analysis, inferential analysis, exemplification, literature summarization and comparative analysis.

Results

According to the analysis of the 35 precedents of jurisdictions from 11 different aspects, it can be seen that the second-instance and retrial rates of this kind of cases are high, and the disputes between patients and medical institutions are fierce. In judicial practice of off-label drug use, medical institutions are determined whether to bear civil liability according to the constituent elements of medical tort liability: the rate of medical institutions’ bearing liability for off-label drug use is not high, and medical institutions are not directly identified as infringing acts and they don’t bear tort liability. The clear provisions about off-label drug use in Law of the People’s Republic of China on Physicians which was implemented in March 2022 confirm this at the legislative level.

Conclusions

By analyzing the current judicial practice of China’s off-label drug use cases, and summarizing the dispute points between medical institution and patients, the constituent elements of tort liability, and the rules of evidence etc., suggestions are proposed to further regulate off-label drug use and promote safe and rational drug use.
DNAJB7 is dispensable for male fertility in mice
Authors: Bai Shun , Hu Meihong , Yu Lina , Chen Linjun , Zhou Jidong , Wu Limin , Xu Bo , Jiang Xiaohua , Zhang Xindong , Tong Xianhong , Yue Qiuling
Published: April 2023

Background

DNAJBs are highly conserved proteins that are involved in various biological processes. Although several DNAJBs are highly expressed in the testis, the function of DNAJB7 in spermatogenesis and male fertility remains unclear.

Methods

To identify the role of DNAJB7 in the male reproduction process, Dnajb7-deficient mice were generated by the CRISPR/Cas9-mediated genome editing system. Histological and immunofluorescence assays were performed to analyze the phenotype of the Dnajb7 mutants.

Results

DNAJB7 is specifically expressed in haploid germ cells. Dnajb7 knockout mice are fertile and do not have any detectable defects in Sertoli cells, spermatogonia, meiotic and postmeiotic cells, indicating that DNAJB7 is not essential for spermatogenesis.

Conclusions

Our findings suggest that DNAJB7 is dispensable for male fertility in mice, which could prevent duplicative work by other groups.
Safety and efficacy of direct oral anticoagulation in patients with and without radiofrequency ablation of non-valvular atrial fibrillation: a multicenter retrospective cohort study
Authors: Wu Shuyi , Guan Chengfu , Xu Wenlin , Zhang Feilong , Huang Nianxu , Chen Xia , Zhang Wang , Hu Wei , Su Jun , Dai Hengfen , Gu Ping , Huang Xiaohong , Du Xiaoming , Li Ruijuan , Zheng Qiaowei , Lin Xiangsheng , Zhang Yanxia , Zou Lang , Liu Yuxin , Zhang Min , Liu Xiumei , Zhu Zhu , Sun Jianjun , Hong Shanshan , She Weibin , Zhang Jinhua
Published: April 2023

Background

Based on the few available studies on the prognostic benefit of using direct oral anticoagulants (DOACs) after atrial fibrillation (AF) ablation. Therefore, this study aimed to evaluate the prognostic differences between patients who underwent radiofrequency ablation (RFA) and those without RFA taking DOACs.

Methods

This is a multicenter retrospective cohort study enrolling 6137 patients with non-valvular AF (NVAF) at 15 hospitals in China. Patient information was collected through a mean follow-up of 10 months and medical record queries. Clinical outcomes included major bleeding, total bleeding, thrombosis, all-cause death, and a composite endpoint of bleeding, thrombosis, and all-cause death.

Results

After adjusting for confounders and propensity score matching (PSM), patients with RFA of NVAF had a significantly lower risk of major bleeding [OR 0.278 (95% CI, 0.150-0.515), P<0.001], thrombosis [OR 0.535 (95% CI, 0.316-0.908), P=0.020] and the composite endpoint [ OR 0.835 (95% CI, 0.710-0.982), P=0.029]. In the RFA PSM cohort, dabigatran was associated with reduced all-cause death in patients with RFA of NVAF [OR 0.420 (95% CI, 0.212-0.831), P=0.010]. In the no RFA PSM cohort, rivaroxaban was associated with a reduction in major bleeding [OR 0.521 (95% CI, 0.403-0.673), P<0.001], total bleeding [OR 0.114 (95% CI, 0.049-0.266), P<0.001], and the composite endpoint [OR 0.659 ( 95% CI, 0.535-0.811), P<0.001].

Conclusion

Among patients with NVAF treated with DOACs, RFA was a negative correlate of major bleeding, thrombosis, and composite endpoints but was not associated with total bleeding or all-cause mortality.
Immediate improvements in post-stroke gait biomechanics are induced with both real-time limb position and propulsive force biofeedback
Authors: Santucci Vincent , Alam Zahin , Liu Justin , Spencer Jacob , Faust Alec , Cobb Aijalon , Konantz Joshua , Eicholtz Steven , Wolf Steven , Kesar Trisha M.
Published: April 2023

Background

Paretic propulsion [measured as anteriorly-directed ground reaction forces (AGRF)] and trailing limb angle (TLA) show robust inter-relationships, and represent two key modifiable post-stroke gait variables that have biomechanical and clinical relevance. Our recent work demonstrated that real-time biofeedback is a feasible paradigm for modulating AGRF and TLA in able-bodied participants. However, the effects of TLA biofeedback on gait biomechanics of post-stroke individuals are poorly understood. Thus, our objective was to investigate the effects of unilateral, real-time, audiovisual TLA versus AGRF biofeedback on gait biomechanics in post-stroke individuals.

Methods

Nine post-stroke individuals (6 males, age 63 ± 9.8 years, 44.9 months post-stroke) participated in a single session of gait analysis comprised of three types of walking trials: no biofeedback, AGRF biofeedback, and TLA biofeedback. Biofeedback unilaterally targeted deficits on the paretic limb. Dependent variables included peak AGRF, TLA, and ankle plantarflexor moment. One-way repeated measures ANOVA with Bonferroni-corrected post-hoc comparisons were conducted to detect the effect of biofeedback on gait biomechanics variables.

Results

Compared to no-biofeedback, both AGRF and TLA biofeedback induced unilateral increases in paretic AGRF. TLA biofeedback induced significantly larger increases in paretic TLA than AGRF biofeedback. AGRF biofeedback increased ankle moment, and both feedback conditions increased non-paretic step length. Both types of biofeedback specifically targeted the paretic limb without inducing changes in the non-paretic limb.

Conclusions

By showing comparable increases in paretic limb gait biomechanics in response to both TLA and AGRF biofeedback, our novel findings provide the rationale and feasibility of paretic TLA as a gait biofeedback target for post-stroke individuals. Additionally, our results provide preliminary insights into divergent biomechanical mechanisms underlying improvements in post-stroke gait induced by these two biofeedback targets. We lay the groundwork for future investigations incorporating greater dosages and longer-term therapeutic effects of TLA biofeedback as a stroke gait rehabilitation strategy.

Trial registrationNCT03466372
Biokinetics of subacutely co-inhaled same size gold and silver nanoparticles
Authors: Lee Philku , Kim Jin Kwon , Jo Mi Seong , Kim Hoi Pin , Ahn Kangho , Park Jung Duck , Gulumian Mary , Oberdörster Günter , Yu Il Je
Published: April 2023

Background

Toxicokinetics of nanomaterials, including studies on the absorption, distribution, metabolism, and elimination of nanomaterials, are essential in assessing their potential health effects. The fate of nanomaterials after inhalation exposure to multiple nanomaterials is not clearly understood.

Methods

Male Sprague–Dawley rats were exposed to similar sizes of silver nanoparticles (AgNPs, 10.86 nm) and gold nanoparticles (AuNPs, 10.82 nm) for 28 days (6-h/day, 5-days/week for four weeks) either with separate NP inhalation exposures or with combined co-exposure in a nose-only inhalation system. Mass concentrations sampled from the breathing zone were AuNP 19.34 ± 2.55 μg/m3 and AgNP 17.38 ± 1.88 μg/m3 for separate exposure and AuNP 8.20 μg/m3 and AgNP 8.99 μg/m3 for co-exposure. Lung retention and clearance were previously determined on day 1 (6-h) of exposure (E-1) and on post-exposure days 1, 7, and 28 (PEO-1, PEO-7, and PEO-28, respectively). In addition, the fate of nanoparticles, including translocation and elimination from the lung to the major organs, were determined during the post-exposure observation period.

Results

AuNP was translocated to the extrapulmonary organs, including the liver, kidney, spleen, testis, epididymis, olfactory bulb, hilar and brachial lymph nodes, and brain after subacute inhalation and showed biopersistence regardless of AuNP single exposure or AuNP + AgNP co-exposure, showing similar elimination half-time. In contrast, Ag was translocated to the tissues and rapidly eliminated from the tissues regardless of AuNP co-exposure. Ag was continually accumulated in the olfactory bulb and brain and persistent until PEO-28.

Conclusion

Our co-exposure study of AuNP and AgNP indicated that soluble AgNP and insoluble AuNP translocated differently, showing soluble AgNP could be dissolved into Ag ion to translocate to the extrapulmonary organs and rapidly removed from most organs except the brain and olfactory bulb. Insoluble AuNPs were continually translocated to the extrapulmonary organs, and they were not eliminated rapidly.
Global health governance performance during Covid-19, what needs to be changed? a delphi survey study
Authors: Abu El Kheir-Mataria Wafa , El-Fawal Hassan , Chun Sungsoo
Published: April 2023

Background

Covid-19 is not the first pandemic to challenge GHG. Preceding outbreaks and epidemics were sources of continuous debate on GHG leadership and structure resulting in its current structure. However, Covid-19 proved the presence of many deficits in the current GHG. The response to the Covid-19 pandemic is a cumulative result of all policies and actions of different governments and agencies active in global health. Assessing how Covid-19 is being handled globally provides lessons for ensuring better performance in facing upcoming outbreaks. This study has three main objectives: first, to evaluate the performance of GHG during Covid-19 in general and in relation to Covid-19 vaccine equity in particular. Second, to identify the reasons behind this performance; and third, to propose prospective changes in GHG for better performance.

Methods

A cross-sectional research design using the Delphi method was applied. A panel of experts participated in the three-round Delphi surveys. Their scores were used to perform consensus, performance and correlation analysis.

Results

GHG performance limited the achievement of Covid-19 vaccines’ global equity. GHG performance is a product of the existing GHG system, its actors and legal framework. It is a collective result of individual GHG actors’ performance. The most influential actors in decision-making regarding Covid-19 vaccine are the vaccine manufacturers and governments. While the most invoked power to influence decision are economic and political powers. Covid-19 decisions underlying value, although had human right to health at the base, overlooked the concept of health as a global public good and was skewed towards market-oriented values. GHG mal-performance along with its underlying factors calls for four main changes in GHG structure: assigning a clear steward for GHG, enhanced accountability, centralized authority, more equitable representation of actors, and better legal framework.

Conclusion

GHG structure, actors’ representation, accountability system, and underlying priorities and value require future modification for GHG to achieve better future performance and higher health equity levels.
Newly developed 3D in vitro models to study tumor–immune interaction
Authors: Mu Peiyuan , Zhou Shujuan , Lv Tao , Xia Fan , Shen Lijun , Wan Juefeng , Wang Yaqi , Zhang Hui , Cai Sanjun , Peng Junjie , Hua Guoqiang , Zhang Zhen
Published: April 2023

Immunotherapy as a rapidly developing therapeutic approach has revolutionized cancer treatment and revitalized the field of tumor immunology research. 3D in vitro models are emerging as powerful tools considering their feature to maintain tumor cells in a near-native state and have been widely applied in oncology research. The novel 3D culture methods including the co-culture of organoids and immune cells, ALI culture, 3D-microfluidic culture and 3D-bioprinting offer new approaches for tumor immunology study and can be applied in many fields such as personalized treatment, immunotherapy optimizing and adoptive cell therapy. In this review, we introduce commonly used 3D in vitro models and summarize their applications in different aspects of tumor immunology research. We also provide a preliminary analysis of the current shortcomings of these models and the outlook of future development.
Targeted next-generation sequencing of 21 candidate genes in hereditary ovarian cancer patients from the Republic of Bashkortostan
Authors: Prokofyeva D. S. , Mingazheva E. T. , Valova Ya. V. , Sakaeva D. D. , Faishanova R. R. , Nurgalieva A. Kh. , Valiev R. R. , Bogdanova N. , Dörk T. , Khusnutdinova E. K.
Published: April 2023

About 5–10% of all ovarian cancer cases show familial clustering, and some 15–25% of familial ovarian cancer cases are mediated by high-penetrance mutations in the BRCA1 and BRCA2 genes. Only few other genes have been identified for familial ovarian cancer.

We conducted targeted next-generation sequencing of the protein coding region of 21 candidate genes, including UTR regions, in genomic DNA samples of 48 patients with familial ovarian cancer from the Republic of Bashkortostan. We identified deleterious variants in BRCA1, BRCA2, CHEK2, MSH6 and NBN in a total of 16 patients (33%). The NBN truncating variant, p.W143X, had not previously been reported. Seven patients (15%) were carriers of the c.5266dupC variant in BRCA1, supporting a Russian origin of this founder allele. An additional 15 variants of uncertain clinical significance were observed. We conclude that our gene panel explains about one-third of familial ovarian cancer risk in the Republic of Bashkortostan.
Lifetime changes in body fatness and breast density in postmenopausal women: the FEDRA study
Authors: Masala Giovanna , Bendinelli Benedetta , Caini Saverio , Duroni Giacomo , Ermini Ilaria , Pastore Elisa , Fontana Miriam , Facchini Luigi , Querci Andrea , Gilio Maria Antonietta , Mazzalupo Vincenzo , Assedi Melania , Ambrogetti Daniela , Palli Domenico
Published: April 2023

Background

High mammographic breast density (MBD) is an established risk factor for breast cancer (BC). Body fatness conveys an increased BC risk in postmenopause but is associated with less dense breasts. Here, we studied the relationship between body fatness and breast composition within the FEDRA (Florence-EPIC Digital mammographic density and breast cancer Risk Assessment) longitudinal study.

Methods

Repeated anthropometric data and MBD parameters (obtained through an automated software on BC screening digital mammograms) were available for all participants, as well as information on other BC risk factors. Multivariate linear regression and functional data analysis were used to longitudinally evaluate the association of body fatness, and changes thereof over time, with dense (DV) and non-dense (NDV) breast volumes and volumetric percent density (VPD).

Results

A total of 5,262 women were included, with anthropometric data available at 20 and 40 years of age, at EPIC baseline (mean 49.0 years), and an average of 9.4 years thereafter. The mean number of mammograms per woman was 3.3 (SD 1.6). Body fatness (and increases thereof) at any age was positively associated with DV and NDV (the association being consistently stronger for the latter), and inversely associated with VPD. For instance, an increase by 1 kg/year between the age of 40 years and EPIC baseline was significantly associated with 1.97% higher DV, 8.85% higher NDV, and 5.82% lower VPD.

Conclusion

Body fatness and its increase from young adulthood until midlife are inversely associated with volumetric percent density, but positively associated with dense and non-dense breast volumes in postmenopausal women.
NSD2 E1099K drives relapse in pediatric acute lymphoblastic leukemia by disrupting 3D chromatin organization
Authors: Narang Sonali , Evensen Nikki A. , Saliba Jason , Pierro Joanna , Loh Mignon L. , Brown Patrick A. , Kolekar Pandurang , Mulder Heather , Shao Ying , Easton John , Ma Xiaotu , Tsirigos Aristotelis , Carroll William L.
Published: April 2023

Background

The NSD2 p.E1099K (EK) mutation is shown to be enriched in patients with relapsed acute lymphoblastic leukemia (ALL), indicating a role in clonal evolution and drug resistance.

Results

To uncover 3D chromatin architecture-related mechanisms underlying drug resistance, we perform Hi-C on three B-ALL cell lines heterozygous for NSD2 EK. The NSD2 mutation leads to widespread remodeling of the 3D genome, most dramatically in terms of compartment changes with a strong bias towards A compartment shifts. Systematic integration of the Hi-C data with previously published ATAC-seq, RNA-seq, and ChIP-seq data show an expansion in H3K36me2 and a shrinkage in H3K27me3 within A compartments as well as increased gene expression and chromatin accessibility. These results suggest that NSD2 EK plays a prominent role in chromatin decompaction through enrichment of H3K36me2. In contrast, we identify few changes in intra-topologically associating domain activity. While compartment changes vary across cell lines, a common core of decompacting loci are shared, driving the expression of genes/pathways previously implicated in drug resistance. We further perform RNA sequencing on a cohort of matched diagnosis/relapse ALL patients harboring the relapse-specific NSD2 EK mutation. Changes in patient gene expression upon relapse significantly correlate with core compartment changes, further implicating the role of NSD2 EK in genome decompaction.

Conclusions

In spite of cell-context-dependent changes mediated by EK, there appears to be a shared transcriptional program dependent on compartment shifts which could explain phenotypic differences across EK cell lines. This core program is an attractive target for therapeutic intervention.
Quantifying the impact of the COVID-19 pandemic on clinical trial screening rates over time in 37 countries
Authors: McDonald Kelsey , Seltzer Earl , Lu Mary , Gaisenband Stefan Diaz , Fletcher Cassandra , McLeroth Patrick , Saini Kamal S
Published: April 2023

The COVID-19 pandemic has had an unprecedented and disruptive impact on people’s health and lives worldwide. In addition to burdening people’s health in the short-term in the form of infection, illness, and mortality, there has been an enormous negative impact on clinical research. Clinical trials experienced challenges in ensuring patient safety and enrolling new patients throughout the pandemic. Here, we investigate and quantify the negative impact that the COVID-19 pandemic has industry-sponsored clinical trials, both in the USA and worldwide. We find a negative correlation between the severity of the COVID-19 pandemic and clinical trial screening rate, with the relationship being strongest during the first three months of the pandemic compared to the entire duration of the pandemic. This negative statistical relationship holds across therapeutic areas, across states in the USA despite the heterogeneity of responses at the state-level, and across countries. This work has significant implications for the management of clinical trials worldwide in response to the fluctuating severity of COVID-19 moving forward and for future pandemics.
Mechanical overloading-induced miR-325-3p reduction promoted chondrocyte senescence and exacerbated facet joint degeneration
Authors: Zhao Jinyun , Li Chengjun , Qin Tian , Jin Yuxin , He Rundong , Sun Yi , Liu Zhide , Wu Tianding , Duan Chunyue , Cao Yong , Hu Jianzhong
Published: April 2023

Objective

Lumbar facet joint (LFJ) degeneration is one of the main causes of low back pain (LBP). Mechanical stress leads to the exacerbation of LFJ degeneration, but the underlying mechanism remains unknown. This study was intended to investigate the mechanism of LFJ degeneration induced by mechanical stress.

Methods

Here, mice primary chondrocytes were used to screen for key microRNAs induced by mechanical overloading. SA-β-gal staining, qRT-PCR, western blot, and histochemical staining were applied to detect chondrocyte senescence in vitro and in vivo. We also used a dual-luciferase report assay to examine the targeting relationship of miRNA-325-3p (miR-325-3p) and Trp53. By using NSC-207895, a p53 activator, we investigated whether miR-325-3p down-regulated trp53 expression to reduce chondrocyte senescence. A mice bipedal standing model was performed to induce LFJ osteoarthritis. Adeno-associated virus (AAV) was intraarticularly injected to evaluate the effect of miR-325-3p on facet joint degeneration.

Results

We observed chondrocyte senescence both in human LFJ osteoarthritis tissues and mice LFJ after bipedally standing for 10 weeks. Mechanical overloading could promote chondrocyte senescence and senescence-associated secretory phenotype (SASP) expression. MicroRNA-array analysis identified that miR-325-3p was obviously decreased after mechanical overloading, which was further validated by fluorescence in situ hybridization (FISH) in vivo. Dual-luciferase report assay showed that miR-325-3p directly targeted Trp53 to down-regulated its expression. MiR-325-3p rescued chondrocyte senescence in vitro, however, NSC-207895 reduced this effect by activating the p53/p21 pathway. Intraarticular injection of AAV expressing miR-325-3p decreased chondrocyte senescence and alleviated LFJ degeneration in vivo.

Conclusion

Our findings suggested that mechanical overloading could reduce the expression of miR-325-3p, which in turn activated the p53/p21 pathway to promote chondrocyte senescence and deteriorated LFJ degeneration, which may provide a promising therapeutic strategy for LFJ degeneration.
Responsiveness of Persian 12-Item multiple sclerosis walking scale: a replication study
Authors: Naghdi Soofia , Ansari Noureddin Nakhostin , Haghparast Afarin , Nakhostin-Ansari Amin , Khalifeloo Maede , Biglar Mahmoud , Lotfi Roghie , Hasson Scott
Published: April 2023

Objective

To re-explore the responsiveness of the Persian version of Multiple Sclerosis Walking Scale-12 (MSWS-12p) to physiotherapy intervention and determine the minimally clinically important change (MCIC). This study followed a prospective cohort design. Patients with MS (PwMS) underwent physiotherapy treatment for 10 sessions. The outcome measures were the MSWS-12p and Timed 25-Foot Walk test (T25-FW). Data was collected before and after ten sessions of physiotherapy. The effect sizes and the area under receiver operating characteristics curve (AUC) and MCIC were calculated.

Results

Thirty PwMS (16 female, mean age 43.07 years) participated in the study. The effect sizes for MSWS-12p were moderate (0.52, 0.64). The change scores of MSWS-12p showed excellent correlation with the dichotomized smallest detectable change (SDC) criterion (Eta coefficient test = 0.84). There was no correlation between the MSWS-12p total change scores and the T25-FW (r = − 0.14, p = 0.45). The AUC was perfect and the MCIC for the MSWS-12p was calculated 10.0 points. The MSWS-12p is responsive and demonstrates changes after physiotherapy. Changes > 10.0 points on MSWS-12p total score should be considered as true improvement after physiotherapy.
Identification of EGFR mutation status in male patients with non-small-cell lung cancer: role of 18F-FDG PET/CT and serum tumor markers CYFRA21-1 and SCC-Ag
Authors: Jiang Maoqing , Chen Ping , Guo Xiuyu , Zhang Xiaohui , Gao Qiaoling , Zhang Jingfeng , Zhao Guofang , Zheng Jianjun
Published: April 2023

Background

The high incidence of epidermal growth factor receptor (EGFR) mutations is usually found in female patients with lung adenocarcinoma who have never-smoked. However, reports concerning male patients are scarce. Thus, this study aimed to explore a novel approach based on 18F-fluoro-2-deoxy-2-deoxyglucose (18F-FDG) PET/CT and serum tumor markers (STMs) to determine EGFR mutation status in male patients with non-small-cell lung cancer (NSCLC).

Methods

A total of 121 male patients with NSCLC were analyzed between October 2019 and March 2022. All patients underwent 18F-FDG PET/CT scan before treatment and monitored 8 STMs (cytokeratin 19 fragment [CYFRA21-1], squamous cell carcinoma-related antigen [SCC-Ag], carcinoembryonic antigen [CEA], neuron-specific enolase [NSE], carbohydrate antigen [CA] 50, CA125, CA72-4, and ferritin). A comparison was done between EGFR mutant and wild-type patients in terms of the maximum standardized uptake value of primary tumors (pSUVmax) and 8 STMs. We performed receiver operating characteristic (ROC) curve and multiple logistic regression analyses to determine predictors for EGFR mutation status.

Results

EGFR mutations were detected in 39 patients (32.2%). Compared with patients with EGFR wild-type, EGFR-mutant patients had lower concentrations of serum CYRFA21-1 (2.65 vs. 4.01, P = 0.002) and SCC-Ag (0.67 vs. 1.05, P = 0.006). No significant differences of CEA, NSE, CA 50, CA125, CA72-4 and ferritin were found between the two groups. The presence of EGFR mutations was significantly associated with low pSUVmax (< 8.75), low serum SCC-Ag (< 0.79 ng/mL) and CYFRA21-1 (< 2.91 ng/mL) concentrations. The area under ROC curve values were 0.679, 0.655, 0.685 and 0.754, respectively, for low CYFRA21-1, SCC-Ag, pSUVmax and the combination of these three factors.

Conclusions

We demonstrated that low concentrations of CYFRA21-1 and SCC-Ag, as well as low pSUVmax, were associated with EGFR mutations, and that the combination of these factors resulted in a higher differentiation of EGFR mutation status in male patients with NSCLC.
The predictive value of [18F]FDG PET/CT radiomics combined with clinical features for EGFR mutation status in different clinical staging of lung adenocarcinoma
Authors: Gao Jianxiong , Niu Rong , Shi Yunmei , Shao Xiaoliang , Jiang Zhenxing , Ge Xinyu , Wang Yuetao , Shao Xiaonan
Published: April 2023

Background

This study aims to construct radiomics models based on [18F]FDG PET/CT using multiple machine learning methods to predict the EGFR mutation status of lung adenocarcinoma and evaluate whether incorporating clinical parameters can improve the performance of radiomics models.

Methods

A total of 515 patients were retrospectively collected and divided into a training set (n = 404) and an independent testing set (n = 111) according to their examination time. After semi-automatic segmentation of PET/CT images, the radiomics features were extracted, and the best feature sets of CT, PET, and PET/CT modalities were screened out. Nine radiomics models were constructed using logistic regression (LR), random forest (RF), and support vector machine (SVM) methods. According to the performance in the testing set, the best model of the three modalities was kept, and its radiomics score (Rad-score) was calculated. Furthermore, combined with the valuable clinical parameters (gender, smoking history, nodule type, CEA, SCC-Ag), a joint radiomics model was built.

Results

Compared with LR and SVM, the RF Rad-score showed the best performance among the three radiomics models of CT, PET, and PET/CT (training and testing sets AUC: 0.688, 0.666, and 0.698 vs. 0.726, 0.678, and 0.704). Among the three joint models, the PET/CT joint model performed the best (training and testing sets AUC: 0.760 vs. 0.730). The further stratified analysis found that CT_RF had the best prediction effect for stage I–II lesions (training set and testing set AUC: 0.791 vs. 0.797), while PET/CT joint model had the best prediction effect for stage III–IV lesions (training and testing sets AUC: 0.722 vs. 0.723).

Conclusions

Combining with clinical parameters can improve the predictive performance of PET/CT radiomics model, especially for patients with advanced lung adenocarcinoma.