bluuebunny/crossref_metadata_2025 huggingface dataset:
A school-based educational on-site vaccination intervention for adolescents in an urban area in Germany: feasibility and psychometric properties of instruments in a pilot study
Authors: Bethke Norma , Gellert Paul , Knoll Nina , Weber Niklas , Seybold Joachim
Published: January 2022

Background

Vaccination rates for measles, mumps, and rubella (MMR) and diphtheria, tetanus, pertussis, and polio (Tdap-IPV) are not optimal among German adolescents. Education in combination with easy access to vaccination may be a promising approach to improve vaccination rates. The present paper describes a pilot study of a planned cluster randomized controlled trial (cRCT) in which we aim to improve MMR and Tdap-IPV vaccination rates together with knowledge and self-efficacy in a school setting.

Methods

The study covered 863 students from 41 classes of four schools. The optimization and feasibility of access to schools, recruitment strategies, intervention, and assessment procedures were examined. The course and content of the educational unit were evaluated with a mixed-methods approach. A pre-post measurement design was tested for the vaccination rate in all schools. Additionally, at two schools, improvement in vaccination-related knowledge and perceived self-efficacy were measured by questionnaire pre-educational unit (n=287) and post-educational unit (n=293). The remaining two schools provided only postintervention data. Finally, we evaluated the psychometric properties (i.e., reliability, retest reliability, and change rates) of the questionnaire, applying Cronbach’s alpha, factor analyses, generalized estimating equations and linear mixed models.

Results

The findings of the pilot study indicated good feasibility. Of the total sample, 437 students (50.9%) brought their vaccination cards to school, 68 students received Tdap-IPV vaccinations, and 11 received MMR vaccinations. Out of six knowledge questions, on average, the students had M=2.84 (95% CI [2.69, 3.10]) correct answers before and M=4.45 (95% CI [4.26, 4.64]) after the class. Ranging from 1 to 4, the self-efficacy scale changed by 0.3 points (p <.001); Cronbach’s alpha was 0.67 and 0.76 pre- and post-educational unit, respectively, and a one-factor solution was found. Content analysis of the five semistructured group interviews (n=12, 58.3% female) showed that all students found the length of the intervention to be appropriate. The teaching methods, including interactive and social media components, were perceived as very good.

Conclusions

A school-based educational and on-site vaccination intervention appears to be feasible in terms of procedures and the adequacy of the instruments for the adolescent target group.

Trial registration

ISRCTN, ISRCTN18026662. Pilot study for main trial registered 8 December 2017.
Interstitial lung disease is not rare in immune-mediated necrotizing myopathy with anti-signal recognition particle antibodies
Authors: Ge Yongpeng , Yang Hanbo , Xiao Xinyue , Liang Lin , Lu Xin , Wang Guochun
Published: January 2022

Objectives

The purpose was to clarify the characteristics of interstitial lung disease (ILD) in immune-mediated necrotizing myopathy (IMNM) patients with anti-signal recognition particle (SRP) antibodies.

Methods

Medical records of IMNM patients with anti-SRP antibodies were reviewed retrospectively.

Results

A total of 60 patients were identified. Twenty-seven (45.0%) patients were diagnosed with ILD based on lung imaging: nonspecific interstitial pneumonia (NSIP) in 17 patients (63.0%) and organizing pneumonia in 9 patients (33.3%). Reticulation pattern was identified in 17 patients (63.0%) whereas 10 cases (37.0%) showed ground glass opacity and patchy shadows by high-resolution computed tomography (HRCT). Pulmonary function tests (PFTs) were available in 18 patients, 6 (33.3%) and 10 (55.6%) patients were included in the mild and moderate group, respectively. The average age at the time of ILD onset was significantly older than those without ILD (48.6 ± 14.4 years vs. 41.2 ± 15.4 years,p < 0.05), and the frequency of dysphagia in the ILD group was higher than the group without ILD (p < 0.05). Long-term follow-up was available on 9 patients. PFTs were stable in 8 (88.9%), and the HRCT remained stable in 6 (66.7%) patients.

Conclusions

ILD is not rare in IMNM patients with anti-SRP antibodies, most being characterized as mild to moderate in severity. NSIP is the principal radiologic pattern, and ILD typically remains stable following treatment.
Effect of subacromial erosion shape on rotator cuff and clinical outcomes after hook plate fixation in type 5 acromioclavicular joint dislocations: a retrospective cohort study
Authors: Oh Ho-Seok , Kim Sungmin , Hyun Jeong-Hun , Kim Myung-Sun
Published: January 2022

Background

Surgical fixation using hook plates is widely used in the treatment of acromioclavicular (AC) joint dislocations. The purpose of this study was to evaluate the incidence and shape of subacromial erosions after removal of the hook plate in type 5 AC joint dislocations. Further, we evaluated the effect of the shape of the subacromial erosion on the rotator cuff.

Methods

We retrospectively reviewed 30 patients who underwent hook plate fixation for type 5 AC joint dislocations at our hospital between December 2010 and December 2018. Patients with a follow-up of at least 1 year were included. Clinical outcomes were assessed using the final follow-up Constant-Murley, Korean Shoulder, and visual analog scores. To ensure that the appropriate reduction was well maintained, the coracoclavicular distances of the injured and contralateral sides were evaluated at the last follow-up. Computed tomography was performed to investigate the presence and shape of the subacromial erosion after hook plate removal at 4 months after surgery. Ultrasonography was performed to investigate the presence of rotator cuff lesions at the last follow-up. Clinical and radiological outcomes were compared between groups divided according to the presence and types of subacromial erosions.

Results

Subacromial erosion was observed in 60% of patients (18/30): 13, 2, and 3 simple groove, cave, and marginal protrusion types, respectively. Four patients showed reduction loss at the final follow-up. There were no significant differences in clinical and radiological outcomes between the groups with and without subacromial erosion. Moreover, there were no significant differences between groups according to the types of subacromial erosion. There were no rotator cuff lesions, such as partial tears, in the injured shoulders.

Conclusions

Hook plate fixation may induce subacromial erosions. However, the subacromial erosions caused by the hook plate did not affect the clinical outcomes of type 5 AC joint dislocations. Moreover, regardless of its shape, the subacromial erosion did not affect the clinical outcomes nor cause rotator cuff lesions after plate removal.
Ossifying fibrous epulis as an IgG4-related disease of the oral cavity: a case report and literature review
Authors: Ike Yoshiko , Shimizu Takahiro , Ogawa Masaru , Yamaguchi Takahiro , Suzuki Keisuke , Takayama Yu , Makiguchi Takaya , Iwashina Masanori , Yokoo Satoshi
Published: January 2022

Background

Fibrous sclerosing tumours and hypertrophic lesions in IgG4-related disease (IgG4-RD) are formed in various organs throughout the body, but disease in the oral region is not included among individual organ manifestations. We report a case of ossifying fibrous epulis that developed from the gingiva, as an instance of IgG4-RD.

Case presentation

A 60-year-old Japanese man visited the Department of Oral and Maxillofacial Surgery, Gunma University Hospital, with a chief complaint of swelling of the left mandibular gingiva. A 65 mm × 45 mm pedunculated tumour was observed. The bilateral submandibular lymph nodes were enlarged. The intraoperative pathological diagnosis of the enlarged cervical lymph nodes was inflammation. Based on this diagnosis, surgical excision was limited to the intraoral tumour, which was subsequently pathologically diagnosed as ossifying fibrous epulis. Histopathologically, the ossifying fibrous epulis exhibited increased levels of fibroblasts and collagen fibres, as well as infiltration by numerous plasma cells. The IgG4/IgG cell ratio was > 40%. Serologic analysis revealed hyper-IgG4-emia (> 135 mg/dL). The patient met the comprehensive clinical diagnosis criteria and the American College of Rheumatology and European League Against Rheumatism classification criteria for IgG4-RD. Based on these criteria, we diagnosed the ossifying fibrous epulis in our patient as an IgG4-related disease. A pathological diagnosis of IgG4-related lymphadenopathy was established for the cervical lymph nodes. Concomitant clinical findings were consistent with type II IgG4-related lymphadenopathy.

Conclusions

A routine serological test may be needed in cases with marked fibrous changes (such as epulis) in the oral cavity and plasma cells, accompanied by tumour formation, to determine the possibility of individual-organ manifestations of IgG4-related disease.
Communication in the face of death and dying - how does the encounter with death influence the patient management competence of medical students? An outcome-evaluation
Authors: Thyson T. , Schallenburger M. , Scherg A. , Leister A. , Schwartz J. , Neukirchen M.
Published: January 2022

Background information

As part of an elective course, the Interdisciplinary Centre for Palliative Medicine at Duesseldorf University Hospital offers medical students the opportunity to personally meet and talk to a seriously ill patient on one or more occasions. The future physicians are provided with an opportunity to broaden their professional competence, i.e. their knowledge and skills in patient-centred communication at the end of life, and enhance their personal competence, for example in how to professionally handle their own emotions. A topical e-learning module helps the students to prepare for the meetings, and writing a reflection paper forms the basis for the concluding reflection seminar.

Objectives

The study’s objective is a global and outcome-based evaluation of the elective blended-learning course that provides real-world patient interaction. The outcome-based evaluation or outcome assessment aims to objectively evaluate changes identified in knowledge, skills and attitude among the participants of the elective-course. Furthermore, the evaluation aims to answer the question of whether changes especially in attitude (social skills and self-competence) should be expected after the students have met with severely ill or dying patients.

Method

On two questionnaires specifically developed for this survey the students were able to provide a global rating of the elective course and describe their learning gains in palliative care. The students’ learning gains were measured by means of 14 items reflecting the specific educational objectives of the offered elective course. Using the German school grading system as a rating scale, the students assessed their learning progress by retrospectively evaluating their skills before and after completion of the elective course (Comparative Self-Assessment, CSA).

Results

In the time from April 2018 till March 2020, 62 students participated in the evaluation. Overall, learning progress among students could be observed across all areas of competence, and in 50% of all retrospective self-assessment items the learning gains were ≥ 50%. The highest learning gain (63.6%) was observed in the students’ ability to meet a severely ill patient without fear. The lowest learning gain was observed when students had to confront and accept their own mortality.

Conclusions

The offered elective course supports students in achieving social and self-competence development goals. According to the obtained results, contact with real-world patients helps mould the students’ attitude.
Variations of a group coaching intervention to support early-career biomedical researchers in Grant proposal development: a pragmatic, four-arm, group-randomized trial
Authors: Weber-Main Anne Marie , Engler Jeffrey , McGee Richard , Egger Marlene J. , Jones Harlan P. , Wood Christine V. , Boman Kristin , Wu Jiqiang , Langi Andrew K. , Okuyemi Kolawole S.
Published: January 2022

Background

Funded grant proposals provide biomedical researchers with the resources needed to build their research programs, support trainees, and advance public health. Studies using National Institutes of Health (NIH) data have found that investigators from underrepresented groups in the biomedical workforce are awarded NIH research grants at disproportionately lower rates. Grant writing training initiatives are available, but there is a dearth of rigorous research to determine the effectiveness of such interventions and to discern their essential features.

Methods

This 2 × 2, unblinded, group-randomized study compares the effectiveness of variations of an NIH-focused, grant writing, group coaching intervention for biomedical postdoctoral fellows and early-career faculty. The key study outcomes are proposal submission rates and funding rates. Participants, drawn from across the United States, are enrolled as dyads with a self-selected scientific advisor in their content area, then placed into coaching groups led by senior NIH-funded investigators who are trained in the intervention’s coaching practices. Target enrollment is 72 coaching groups of 4–5 dyads each. Groups are randomized to one of four intervention arms that differ on two factors: [1] duration of coaching support (regular dose = 5 months of group coaching, versus extended dose = regular dose plus an additional 18 months of one-on-one coaching); and [2] mode of engaging scientific advisors with the regular dose group coaching process (unstructured versus structured engagement). Intervention variations were informed by programs previously offered by the NIH National Research Mentoring Network. Participant data are collected via written surveys (baseline and 6, 12, 18, and 24 months after start of the regular dose) and semi-structured interviews (end of regular dose and 24 months). Quantitative analyses will be intention-to-treat, using a 2-sided test of equality of the effects of each factor. An inductive, constant comparison analysis of interview transcripts will be used to identify contextual factors -- associated with individual participants, their engagement with the coaching intervention, and their institutional setting – that influence intervention effectiveness.

Discussion

Results of this study will provide an empirical basis for a readily translatable coaching approach to supporting the essential grant writing activities of faculty, fellows, and other research trainees, including those from underrepresented groups.
Benefits, risks, and cost-effectiveness of COVID-19 self-tests from a consumer’s perspective
Authors: Gandjour Afschin
Published: January 2022

Background

The aim of this study is to quantify the health benefits, risks, and cost-effectiveness of COVID-19 self-tests from a consumer’s perspective in Germany.

Methods

The analysis is based on a modelling approach using secondary data. The clinical endpoints considered in this analysis are avoided SARS-CoV-2 infections and secondary severe clinical events (death, intensive care unit (ICU) admission, and long COVID syndrome). The study determines the number of self-tests that need to be conducted under a 7-day incidence of 75 per 100,000 population to prevent one infection or severe clinical event. Furthermore, the study calculates the cost of testing per avoided clinical event and quality-adjusted life year (QALY) gained from a consumer perspective.

Results

Disregarding the rate of unreported COVID-19 cases, 4556 self-tests need to be conducted (over 12 years) in order to avoid one undesirable event (death, intensive care unit stay, or long COVID syndrome). Ninety percent of infections are not avoided among direct contacts but along the chain of infection. The costs per quality-adjusted life year gained from a consumer’s perspective are €5870. This ratio is particularly sensitive to the 7-day incidence, effective reproduction number, and the age of contacts.

Conclusions

The benefits of self-testing in the general population at a 7-day incidence rate of 75 per 100,000 appear to be minor. Nevertheless, cost-effectiveness may still be acceptable in the presence of higher-risk contacts given the low costs of self-test kits in Germany.
Exploring the causal role of intimate partner violence and abuse on depressive symptoms in young adults: a population-based cohort study
Authors: Herbert Annie , Heron Jon , Barnes Maria , Barter Christine , Feder Gene , Meghrawi Khadija , Szilassy Eszter , Fraser Abigail , Howe Laura D.
Published: January 2022

Background

Previous studies have shown an association between experience of intimate partner violence and abuse (IPVA) and depression. Whether this is a causal relationship or explained by prior vulnerability that influences the risk of both IPVA and depression is not known.

Methods

We analysed data from the Avon Longitudinal Study of Parents and Children prospective cohort (N = 1764 women, 1028 men). To assess the causal association between IPVA at 18–21 years old and logged depressive symptom scores at age 23, we used (i) multivariable linear regression, (ii) inverse probability of treatment weighting (IPTW), and (iii) difference-in-difference (DiD) analysis, which compared the mean change in logged depressive symptom scores between ages 16 and 23 between those who experienced IPVA and those who did not.

Results

Women who experienced IPVA had on average 26% higher depressive symptom scores after adjustment for measured confounders (ratio of geometric means 1.26, 95% CI 1.13 to 1.40). In men, the difference was 5% (ratio of geometric means 1.05, 95% CI 0.92 to 1.21). Results from IPTW analysis were similar. In the DiD analysis, there was no evidence that being exposed to IPVA affected the change in depressive symptom scores over time compared to being in the non-exposed group for either women (difference-in-differences 1%, −12 to 16%) or men (−1%, −19 to 20%).

Conclusions

Multivariable linear regression and IPTW suggested an association between IPVA and higher depressive symptom score in women but not men, but DiD analysis indicated a null effect in both women and men. This suggests the causal origins of higher depressive symptoms in this young adult population are likely to reflect prior vulnerability that leads to both higher depressive symptoms and increased risk of IPVA exposure.
Acute-phase protein concentrations in serum of clinically healthy and diseased European bison (Bison bonasus) – preliminary study
Authors: Pomorska-Mól Małgorzata , Libera Kacper , Larska Magdalena , Krzysiak Michał K.
Published: January 2022

Background

This is the first report describing levels of APPs in European bison. Serum concentration of acute phase proteins (APPs) may be helpful to assess general health status in wildlife and potentially useful in selecting animals for elimination. Since there is a lack of literature data regarding concentration of APPs in European bisons, establishment of the reference values is also needed.

Methods

A total of 87 European bison from Polish populations were divided into two groups: (1) healthy: immobilized for transportation, placing a telemetry collar and routine diagnostic purposes; and (2) selectively culled due to the poor health condition. The serum concentration of haptoglobin, serum amyloid A and α1-acid-glycoprotein were determined using commercial quantitative ELISA assays. Since none of the variables met the normality assumptions, non-parametric Mann-Whitney U test was used for all comparisons. Statistical significance was set at p < 0.05. Statistical analyses were performed using Statistica 13.3 (Tibco, USA).

Results

The concentration of haptoglobin and serum amyloid A was significantly higher in animals culled (euthanised) due to the poor condition in respect to the clinically healthy European bison. The levels of α1-acid-glycoprotein did not show statistical difference between healthy and sick animals.

Conclusions

Correlation between APPs concertation and health status was proven, therefore the determination of selected APPs may be considered in future as auxiliary predictive tool in assessing European bison health condition.
Monocarboxylate transporter functions and neuroprotective effects of valproic acid in experimental models of amyotrophic lateral sclerosis
Authors: Gyawali Asmita , Latif Sana , Choi Seung-Hye , Hyeon Seung Jae , Ryu Hoon , Kang Young-Sook
Published: January 2022

Background

Amyotrophic lateral sclerosis (ALS) is a devasting neurodegenerative disorder for which no successful therapeutics are available. Valproic acid (VPA), a monocarboxylate derivative, is a known antiepileptic drug and a histone deacetylase inhibitor.

Methods

To investigate whether monocarboxylate transporter 1 (MCT1) and sodium-coupled MCT1 (SMCT1) are altered in ALS cell and mouse models, a cellular uptake study, quantitative real time polymerase chain reaction and western blot parameters were used. Similarly, whether VPA provides a neuroprotective effect in the wild-type (WT; hSOD1WT) and ALS mutant-type (MT; hSOD1G93A) NSC-34 motor neuron-like cell lines was determined through the cell viability assay.

Results

[3H]VPA uptake was dependent on time, pH, sodium and concentration, and the uptake rate was significantly lower in the MT cell line than the WT cell line. Interestingly, two VPA transport systems were expressed, and the VPA uptake was modulated by SMCT substrates/inhibitors in both cell lines. Furthermore, MCT1 and SMCT1 expression was significantly lower in motor neurons of ALS (G93A) model mice than in those of WT mice. Notably, VPA ameliorated glutamate- and hydrogen peroxide-induced neurotoxicity in both the WT and MT ALS cell lines.

Conclusions

Together, the current findings demonstrate that VPA exhibits a neuroprotective effect regardless of the dysfunction of an MCT in ALS, which could help develop useful therapeutic strategies for ALS.
Speed dating for enzymes! Finding the perfect phosphopantetheinyl transferase partner for your polyketide synthase
Authors: Pedersen Tobias Bruun , Nielsen Mikkel Rank , Kristensen Sebastian Birkedal , Spedtsberg Eva Mie Lang , Sørensen Trine , Petersen Celine , Muff Jens , Sondergaard Teis Esben , Nielsen Kåre Lehmann , Wimmer Reinhard , Gardiner Donald Max , Sørensen Jens Laurids
Published: January 2022

The biosynthetic pathways for the fungal polyketides bikaverin and bostrycoidin, from Fusarium verticillioides and Fusarium solani respectively, were reconstructed and heterologously expressed in S. cerevisiae alongside seven different phosphopantetheinyl transferases (PPTases) from a variety of origins spanning bacterial, yeast and fungal origins. In order to gauge the efficiency of the interaction between the ACP-domains of the polyketide synthases (PKS) and PPTases, each were co-expressed individually and the resulting production of target polyketides were determined after 48 h of growth. In co-expression with both biosynthetic pathways, the PPTase from Fusarium verticillioides (FvPPT1) proved most efficient at producing both bikaverin and bostrycoidin, at 1.4 mg/L and 5.9 mg/L respectively. Furthermore, the remaining PPTases showed the ability to interact with both PKS’s, except for a single PKS-PPTase combination. The results indicate that it is possible to boost the production of a target polyketide, simply by utilizing a more optimal PPTase partner, instead of the commonly used PPTases; NpgA, Gsp and Sfp, from Aspergillus nidulans, Brevibacillus brevis and Bacillus subtilis respectively.
miR-133a targets YES1 to reduce cisplatin resistance in ovarian cancer by regulating cell autophagy
Authors: Zhou Yang , Wang Chunyan , Ding Jinye , Chen Yingying , Sun Yaoqi , Cheng Zhongping
Published: January 2022

Background

Accumulating evidence has revealed that aberrant microRNA (miRNA) expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. Emerging evidence has demonstrated that miR-133a participates in the tumorigenesis of various cancers. However, whether miR-133a is associated with cisplatin resistance in ovarian cancer remains unclear.

Objective

To investigate the role of miR-133a in the development of cisplatin resistance in ovarian cancer.

Methods

MiR-133a expression in cisplatin-resistant ovarian cancer cell lines was assessed by reverse-transcription quantitative PCR (RT–qPCR). A cell counting kit-8 (CCK-8) assay was used to evaluate the viability of tumour cells treated with cisplatin in the presence or absence of miR-133a. A luciferase reporter assay was used to analyse the binding of miR-133a with the 3′ untranslated region (3′UTR) of YES proto-oncogene 1 (YES1). The YES1 expression level was analysed using a dataset from the International Cancer Genome Consortium (ICGC) and assessed by RT–qPCR and western blotting in vitro. The roles and mechanisms of YES1 in cell functions were further probed via gain- and loss-of-function analysis.

Results

The expression of miR-133a was significantly decreased in cisplatin-resistant ovarian cancer cell lines (A2780-DDP and SKOV3-DDP), and the overexpression of the miR-133a mimic reduced cisplatin resistance in A2780-DDP and SKOV3-DDP cells. Treatment with the miR-133a inhibitor increased cisplatin sensitivity in normal A2780 and SKOV3 cells. MiR-133a binds the 3’UTR of YES1 and downregulates its expression. Bioinformatics analysis revealed that YES1 expression was upregulated in recurrent cisplatin-resistant ovarian cancer tissue, and in vitro experiments also verified its upregulation in cisplatin-resistant cell lines. Furthermore, we discovered that miR-133a downregulated the expression of YES1 and thus inhibited cell autophagy to reduce cisplatin resistance. Yes1 knockdown significantly suppressed the cisplatin resistance of ovarian cancer cells by inhibiting autophagy in vitro. Xenograft tumour implantation further demonstrated that Yes1 overexpression promoted ovarian tumour development and cisplatin resistance.

Conclusions

Our results suggest that the miR-133a/YES1 axis plays a critical role in cisplatin resistance in human ovarian cancer by regulating cell autophagy, which might serve as a promising therapeutic target for ovarian cancer chemotherapy treatment in the future.
“We are not stray leaves blowing about in the wind”: exploring the impact of Family Wellbeing empowerment research, 1998–2021
Authors: Perera Nirukshi , Tsey Komla , Heyeres Marion , Whiteside Mary , Baird Leslie , McCalman Janya , Cadet-James Yvonne , Calabria Bianca , Hamilton Michael , Yan Li , Zuchowski Ines , Sims Kearrin , Udah Hyacinth
Published: January 2022

Background

An Aboriginal-developed empowerment and social and emotional wellbeing program, known as Family Wellbeing (FWB), has been found to strengthen the protective factors that help Indigenous Australians to deal with the legacy of colonisation and intergenerational trauma. This article reviews the research that has accompanied the implementation of the program, over a 23 year period. The aim is to assess the long-term impact of FWB research and identify the key enablers of research impact and the limitations of the impact assessment exercise. This will inform more comprehensive monitoring of research impact into the future.

Methods

To assess impact, the study took an implementation science approach, incorporating theory of change and service utilisation frameworks, to create a logic model underpinned by Indigenous research principles. A research impact narrative was developed based on mixed methods analysis of publicly available data on: 1) FWB program participation; 2) research program funding; 3) program outcome evaluation (nine studies); and 4) accounts of research utilisation (seven studies).

Results

 Starting from a need for research on empowerment identified by research users, an investment of $2.3 million in research activities over 23 years produced a range of research outputs that evidenced social and emotional wellbeing benefits arising from participation in the FWB program. Accounts of research utilisation confirmed the role of research outputs in educating participants about the program, and thus, facilitating more demand (and funding acquisition) for FWB. Overall research contributed to 5,405 recorded participants accessing the intervention. The key enablers of research impact were; 1) the research was user- and community-driven; 2) a long-term mutually beneficial partnership between research users and researchers; 3) the creation of a body of knowledge that demonstrated the impact of the FWB intervention via different research methods; 4) the universality of the FWB approach which led to widespread application.

Conclusions

The FWB research impact exercise reinforced the view that assessing research impact is best approached as a “wicked problem” for which there are no easy fixes. It requires flexible, open-ended, collaborative learning-by-doing approaches to build the evidence base over time. Steps and approaches that research groups might take to build the research impact knowledge base within their disciplines are discussed.
Prenatal exposure to organophosphate pesticides and risk-taking behaviors in early adulthood
Authors: Sagiv Sharon K. , Rauch Stephen , Kogut Katherine R. , Hyland Carly , Gunier Robert B. , Mora Ana M. , Bradman Asa , Deardorff Julianna , Eskenazi Brenda
Published: January 2022

Introduction

Previous studies show evidence for associations of prenatal exposure to organophosphate (OP) pesticides with poorer childhood neurodevelopment. As children grow older, poorer cognition, executive function, and school performance can give rise to risk-taking behaviors, including substance abuse, delinquency, and violent acts. We investigated whether prenatal OP exposure was associated with these risk-taking behaviors in adolescence and young adulthood in a Mexican American cohort.

Methods

We measured urinary dialkyl phosphates (DAPs), non-specific metabolites of OPs, twice (13 and 26 weeks gestation) in pregnant women recruited in 1999–2000 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a birth cohort set in a primarily Latino agricultural community in the Salinas Valley, California. We followed up children throughout their childhood and adolescence; at the 18-year visit, adolescent youth (n = 315) completed a computer-based questionnaire which included questions about substance use, risky sexual activity, risky driving, and delinquency and police encounters. We used multivariable models to estimate associations of prenatal total DAPs with these risk-taking behaviors.

Results

The prevalence of risk-taking behaviors in CHAMACOS youth ranged from 8.9% for smoking or vaping nicotine to 70.2% for committing a delinquent act. Associations of total prenatal DAPs (geometric mean = 132.4 nmol/L) with risk-taking behavior were generally null and imprecise. Isolated findings included a higher risk for smoking or vaping nicotine within the past 30 days (relative risk [RR] per 10-fold increase in prenatal DAPs = 1.89, 95% CI: 1.00, 3.56) and driving without a license (RR = 1.74, 95% CI: 1.25, 2.42). There were no consistent differences by sex or childhood adversity.

Discussion

We did not find clear or consistent evidence for associations of prenatal OP exposure with risk-taking behaviors in adolescence/early adulthood in the CHAMACOS population. Our small sample size may have prevented us from detecting potentially subtle associations of early life OP exposure with these risk-taking behaviors.
3D hanging spheroid plate for high-throughput CAR T cell cytotoxicity assay
Authors: Chen Zhenzhong , Han Seokgyu , Sanny Arleen , Chan Dorothy Leung-Kwan , van Noort Danny , Lim Wanyoung , Tan Andy Hee-Meng , Park Sungsu
Published: January 2022

Background

Most high-throughput screening (HTS) systems studying the cytotoxic effect of chimeric antigen receptor (CAR) T cells on tumor cells rely on two-dimensional cell culture that does not recapitulate the tumor microenvironment (TME). Tumor spheroids, however, can recapitulate the TME and have been used for cytotoxicity assays of CAR T cells. But a major obstacle to the use of tumor spheroids for cytotoxicity assays is the difficulty in separating unbound CAR T and dead tumor cells from spheroids. Here, we present a three-dimensional hanging spheroid plate (3DHSP), which facilitates the formation of spheroids and the separation of unbound and dead cells from spheroids during cytotoxicity assays.

Results

The 3DHSP is a 24-well plate, with each well composed of a hanging dripper, spheroid wells, and waste wells. In the dripper, a tumor spheroid was formed and mixed with CAR T cells. In the 3DHSP, droplets containing the spheroids were deposited into the spheroid separation well, where unbound and dead T and tumor cells were separated from the spheroid through a gap into the waste well by tilting the 3DHSP by more than 20°. Human epidermal growth factor receptor 2 (HER2)-positive tumor cells (BT474 and SKOV3) formed spheroids of approximately 300–350 μm in diameter after 2 days in the 3DHSP. The cytotoxic effects of T cells engineered to express CAR recognizing HER2 (HER2-CAR T cells) on these spheroids were directly measured by optical imaging, without the use of live/dead fluorescent staining of the cells. Our results suggest that the 3DHSP could be incorporated into a HTS system to screen for CARs that enable T cells to kill spheroids formed from a specific tumor type with high efficacy or for spheroids consisting of tumor types that can be killed efficiently by T cells bearing a specific CAR.

Conclusions

The results suggest that the 3DHSP could be incorporated into a HTS system for the cytotoxic effects of CAR T cells on tumor spheroids.

Graphical Abstract
Anxiety disorders in patients with noncardiac chest pain: association with health-related quality of life and chest pain severity
Authors: Hamel Stéphanie , Denis Isabelle , Turcotte Stéphane , Fleet Richard , Archambault Patrick , Dionne Clermont E. , Foldes-Busque Guillaume
Published: January 2022

Background

Patients with noncardiac chest pain (NCCP) report more severe symptoms and lowered health-related quality of life when they present with comorbid panic disorder (PD). Although generalized anxiety disorder (GAD) is the second most common psychiatric disorder in these patients, its impact on NCCP and health-related quality of life remains understudied. This study describes and prospectively compares patients with NCCP with or without PD or GAD in terms of (1) NCCP severity; and (2) the physical and mental components of health-related quality of life.

Methods

A total of 915 patients with NCCP were consecutively recruited in two emergency departments. The presence of comorbid PD or GAD was assessed at baseline with the Anxiety Disorder Schedule for DSM-IV. NCCP severity at baseline and at the six-month follow-up was assessed with a structured telephone interview, and the patients completed the 12-item Short-Form Health Survey Version 2 (SF-12v2) to assess health-related quality of life at both time points.

Results

Average NCCP severity decreased between baseline and the six-month follow-up (p < .001) and was higher in the patients with comorbid PD or GAD (p < .001) at both time points compared to those with NCCP only. However, average NCCP severity did not differ between patients with PD and those with GAD (p = 0.901). The physical component of quality of life improved over time (p = 0.016) and was significantly lower in the subset of patients with PD with or without comorbid GAD compared to the other groups (p < .001). A significant time x group interaction was found for the mental component of quality of life (p = 0.0499). GAD with or without comorbid PD was associated with a lower mental quality of life, and this effect increased at the six-month follow-up.

Conclusions

Comorbid PD or GAD are prospectively associated with increased chest pain severity and lowered health-related quality of life in patients with NCCP. PD appears to be mainly associated with the physical component of quality of life, while GAD has a greater association with the mental component. Knowledge of these differences could help in the management of patients with NCCP and these comorbidities.
Accreditation and professional integration experiences of internationally qualified dentists working in the United Kingdom
Authors: Davda Latha S. , Radford David R. , Scambler Sasha , Gallagher Jennifer E.
Published: January 2022

Introduction

Regulatory processes for Oral health care professionals are considered essential for patient safety and to ensure health workforce quality. The global variation in their registration and regulation is under-reported in the literature. Regulatory systems could become a barrier to their national and international movement, leading to loss of skilled human resources. The General Dental Council is the regulatory authority in the UK, one of the nine regulators of health care overseen by the Professional Standards Authority.

Aim

The aim of this paper is to present the professional integration experiences of internationally qualified dentists (IQDs) working in the UK, against the background of regulation and accreditation nationally.

Methods

Registration data were obtained from the General Dental Council to inform the sampling and recruitment of research participants. Semi-structured interviews of 38 internationally qualified dentists working in the United Kingdom were conducted between August 2014 and October 2017. The topic guide which explored professional integration experiences of the dentists was informed by the literature, with new themes added inductively. A phenomenological approach involving an epistemological stance of interpretivism, was used with framework analysis to detect themes.

Results

Internationally qualified dentist’s professional integration was influenced by factors that could be broadly classified as structural (source country training; registration and employment; variation in practising dentistry) and relational (experiences of discrimination; value of networks and support; and personal attributes). The routes to register for work as a dentist were perceived to favour UK dental graduates and those qualifying from the European Economic Area. Dentists from the rest of the world reported experiencing major hurdles including succeeding in the licensing examinations, English tests, proving immigration status and succeeding in obtaining a National Health Service performer number, all prior to being able to practice within state funded dental care.

Conclusion

The pathways for dentists to register and work in state funded dental care in UK differ by geographic type of registrant, creating significant inconsistencies in their professional integration. Professional integration is perceived by an individual IQD as a continuum dictated by host countries health care systems, workforce recruitment policies, access to training, together with their professional and personal skills. The reliance of the UK on internationally qualified dentists has increased in the past two decades, however, it is not known how these trends will be affected by UK’s exit from the European Union and the COVID-19 pandemic.
Immunological status of the olfactory bulb in a murine model of Toll-like receptor 3-mediated upper respiratory tract inflammation
Authors: Kagoya Ryoji , Toma-Hirano Makiko , Yamagishi Junya , Matsumoto Naoyuki , Kondo Kenji , Ito Ken
Published: January 2022

Background

Postviral olfactory dysfunction (PVOD) following a viral upper respiratory tract infection (URI) is one of the most common causes of olfactory disorders, often lasting for over a year. To date, the molecular pathology of PVOD has not been elucidated.

Methods

A murine model of Toll-like receptor 3 (TLR3)-mediated upper respiratory tract inflammation was used to investigate the impact of URIs on the olfactory system. Inflammation was induced via the intranasal administration of polyinosinic–polycytidylic acid (poly(I:C), a TLR3 ligand) to the right nostril for 3 days. Peripheral olfactory sensory neurons (OSNs), immune cells in the olfactory mucosa, and glial cells in the olfactory bulb (OB) were analyzed histologically. Proinflammatory cytokines in the nasal tissue and OB were evaluated using the quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA).

Results

In the treated mice, OSNs were markedly reduced in the olfactory mucosa, and T cell and neutrophil infiltration therein was observed 1 day after the end of poly(I:C) administration. Moreover, there was a considerable increase in microglial cells and slight increase in activated astrocytes in the OB. In addition, qPCR and ELISA revealed the elevated expression of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma both in the OB and nasal tissue.

Conclusions

Taken together, the decreased peripheral OSNs, OB microgliosis, and elevated proinflammatory cytokines suggest that immunological changes in the OB may be involved in the pathogenesis of PVOD.
Death-stricken survivor mother: the lived experience of near miss mothers
Authors: Abdollahpour Sedigheh , Heydari Abbas , Ebrahimipour Hosein , Faridhoseini Farhad , Khadivzadeh Talat
Published: January 2022

Background

A Near Miss Mother (NMM) who survives life-threatening conditions, experiences intense physical, emotional, and psychological consequences following the maternal near-miss (MNM) events. The aim of this study was therefore to explore indepth understanding meaning of NMM everyday lived experiences on the social and cultural background of Iran.

Methods

This qualitative study utilized a hermeneutic phenomenology procedure. The study was conducted in hospitals affiliated with the Educational, Research and Treatment Centerwhich usually handle the NMMs. The sampling was purposeful with a maximum variation of eleven NMMs. Datawere collected using unstructured face-to-face interviews, and thetranscribed data were analyzed using Diekelmann, Allen, and Tanner’s seven-stage thematic analysis approach.

Results

"Death-stricken survivor mother" was the central emerged theme, and three extracted sub-themes included: "Distorted psyche on a journey to death", "physical destruction due to an ominous event ", and the "vicissitudinous life after reviving ". These sub-themes, in turn, involved 12 sub-themes that emerged from 38 common meanings and 1200 codes.

Conclusions

Findings demonstrate that the living conditions of NMMs are mixed in all aspects of the MNM event. They need a supportive program that includes additional follow-up visits, psychological support from the time of hospitalization until long-time after discharge, alleviation of social, sexual, and financial worries to return them to the normal life, as well as psychosocial rehabilitation to increase their life quality. Furthermore, post-discharge care in NMMs should be done actively and directly at their homes.
Chronic effects of blast injury on the microvasculature in a transgenic mouse model of Alzheimer’s disease related Aβ amyloidosis
Authors: Clark Alexander T. , Abrahamson Eric E. , Harper Matthew M. , Ikonomovic Milos D.
Published: January 2022

Background

Altered cerebrovascular function and accumulation of amyloid-β (Aβ) after traumatic brain injury (TBI) can contribute to chronic neuropathology and increase the risk for Alzheimer’s disease (AD). TBI due to a blast-induced shock wave (bTBI) adversely affects the neurovascular unit (NVU) during the acute period after injury. However, the chronic effects of bTBI and Aβ on cellular components of the NVU and capillary network are not well understood.

Methods

We exposed young adult (age range: 76–106 days) female transgenic (Tg) APP/PS1 mice, a model of AD-like Aβ amyloidosis, and wild type (Wt) mice to a single bTBI (~ 138 kPa or ~ 20 psi) or to a Sham procedure. At 3-months or 12-months survival after exposure, we quantified neocortical Aβ load in Tg mice, and percent contact area between aquaporin-4 (AQP4)-immunoreactive astrocytic end-feet and brain capillaries, numbers of PDGFRβ-immunoreactive pericytes, and capillary densities in both genotypes.

Results

The astroglia AQP4-capillary contact area in the Tg-bTBI group was significantly lower than in the Tg-Sham group at 3-months survival. No significant changes in the AQP4-capillary contact area were observed in the Tg-bTBI group at 12-months survival or in the Wt groups. Capillary density in the Tg-bTBI group at 12-months survival was significantly higher compared to the Tg-Sham control and to the Tg-bTBI 3-months survival group. The Wt-bTBI group had significantly lower capillary density and pericyte numbers at 12-months survival compared to 3-months survival. When pericytes were quantified relative to capillary density, no significant differences were detected among the experimental groups, for both genotypes.

Conclusion

In conditions of high brain concentrations of human Aβ, bTBI exposure results in reduced AQP4 expression at the astroglia-microvascular interface, and in chronic capillary proliferation like what has been reported in AD. Long term microvascular changes after bTBI may contribute to the risk for developing chronic neurodegenerative disease later in life.
Magnetic resonance findings may aid in diagnosis of protracted febrile myalgia syndrome: a retrospective, multicenter study
Authors: Aviran Neta , Amarilyo Gil , Lakovsky Yaniv , Tal Rotem , Garkaby Jenny , Haviv Rubi , Uziel Yosef , Spielman Shiri , Natour Hamada Mohammad , Herman Yonatan , Scheuerman Oded , Butbul Aviel Yonatan , Levinsky Yoel , Harel Liora
Published: January 2022

Background

Protracted febrile myalgia syndrome (PFMS) is a rare complication of Familial Mediterranean fever (FMF). The diagnosis is based on clinical symptoms and is often challenging, especially when PFMS is the initial manifestation of FMF. The aim of this report was to describe the magnetic resonance imaging (MRI) findings in pediatric patients with PFMS.

Results

There were three girls and two boys ranging in age from 6 months to 16 years, all of Mediterranean ancestry. Three had high-grade fever, and all had elevated inflammatory markers. MRI of the extremities yielded findings suggestive of myositis, which together with the clinical picture, normal CPK levels, and supporting family history of FMF, suggested the diagnosis of PFMS. Out of most common MEFV mutations tested, one patient was homozygous for M694V mutation, three were heterozygous for M694V mutation, and one was compound heterozygous for the M694V and V726A mutations.

Conclusions

MRI may serve as an auxiliary diagnostic tool in PFMS.
Descriptive review of internet-based cognitive behavior therapy on anxiety-related problems in children under the circumstances of COVID-19
Authors: Shirotsuki Kentaro , Sugaya Nagisa , Nakao Mutsuhiro
Published: January 2022

Background

COVID-19 continues to have a global impact and has yet to converge. Behavioral restrictions in daily life are widespread, forcing changes to the behavioral patterns of people. Significant changes have also occurred in children’s lives, raising concerns about mental health. The same is true for anxiety symptoms.

Research

In this paper, we described the COVID-19 pandemic effects on mental health, summarized Internet-based cognitive behavioral therapy (ICBT) as an applicability of cognitive behavioral therapy (CBT) for COVID-19, and summarized ICBT’s current state as a response for anxiety. An overview of previous intervention studies, including randomized controlled trials (RCTs) on ICBT, showed that many studies were highly effective against anxiety symptoms. Furthermore, regarding the follow-up of ICBT’s intervention effect, long-term effect maintenance was also clarified. It was likewise pointed out that ICBT may be used in the future since it is beneficial for children’s anxiety symptoms in telemedicine.

Conclusions

Based on these results from previous studies, we discuss ICBT’s applicability during the COVID-19 pandemic. Additionally, future measures and prospects for children’s mental health during the pandemic are discussed in this study.