bluuebunny/crossref_metadata_2025 huggingface dataset:
Childhood adversity subtypes and violence victimization and perpetration among early adolescents in Shanghai, China
Authors: Zuo Xiayun , Zhang Ziwei , Yan Li , Lian Qiguo , Yu Chunyan , Tu Xiaowen , Lou Chaohua
Published: September 2021

Background

This cross-sectional study aimed to identify adverse childhood experience (ACE) subtypes using variable- and person-centered approaches and examine the possible sex-differentiated associations with violence involvement as victim, perpetrator, and victim-perpetrator.

Methods

Adolescents aged 10–14 years in three junior high schools in Shanghai, China, were selected using a cluster sampling method in November and December 2017. Participants were surveyed anonymously using a computer-assisted self-interview approach via tablets. Thirteen items modified from the CDC-Kaiser ACE study were used to measure the ACEs. Results show subtypes as neglect, abuse, and household dysfunction by developing cumulative index score from the variable perspective and subgroups identified through the latent class analysis (LCA) from the person perspective. Logistic regression analyses were used to test the association between each ACE subtype and violence victimization and perpetration after adjusting for some demographic characteristics.

Results

A total of 1,700 participants were included in the final analysis. Approximately 1,322 (77.76 %) participants reported experiencing at least one ACE. The prevalence of neglect, abuse, and household dysfunction was 64.12 % (n = 1090), 61.29 % (n = 1042), and 18.24 % (n = 310), respectively. Three classes were identified through the LCA: low exposure to all ACEs (n = 854, 50.23 %), high exposure to emotional and physical abuse and neglect (n = 715, 42.06 %), and high exposure to all ACEs (n = 131,7.71 %). After controlling the covariates, experiencing abuse, neglect, and household dysfunction was significantly related to violence victimization (adjusted odds ratio [aOR] = 3.19, 3.29, 2.37, P < 0.001) and victim-perpetrator (aOR = 3.48, 4.41, 5.16, P < 0.001). Adolescent violence perpetration was only found to be associated with being neglected (aOR = 2.37, P = 0.003) and suffering household dysfunction (aOR = 3.25, P < 0.001). LCA revealed the cumulative effects of ACEs on adolescent violence victimization and perpetration. Sex-stratified analysis indicate that girls were more vulnerable to the negative effects of ACEs, with a higher risk of perpetration among girls exposed to distinctive subtypes or multiple ACEs.

Conclusions

ACEs were ubiquitous and significantly associated with an elevated risk of violence victimization and perpetration during early adolescence. Future research should examine whether these associations persist over time and the intermediating mechanism from the perspectives of individual neurodevelopment, cognition and resilience ability, and social support.
Young men and young women in secure care: gender differences in the placement of those with mental health needs
Authors: Bartlett Annie , Smith Jared G. , Warner Louise , Hales Heidi
Published: September 2021

Background

The system of secure care for young people in England and Wales comprises youth justice, welfare and mental health facilities. Empirical studies have failed to investigate the system as a whole. The National Adolescent Study in 2016 was the first to provide comprehensive system wide information. This paper, derived from that data set, addresses equity of service provision for young men and women in secure care who have mental health problems.

Methods

The detained census population of English young people in 2016 was 1322 and detailed data were available on 93% of this population, including 983 young men and 290 young women. The descriptive census data were interrogated to identify associations between gender, other sociodemographic and clinical variables, using Chi-square and Fisher’s exact tests.

Results

Numerically more young men in secure care than young women in secure care warrant a psychiatric diagnosis but young women had a 9 fold increase in the odds of having a diagnosis compared with the young men. The pattern of mental health diagnoses differed significantly by gender as did the legislative framework under which females and males were placed. This different pattern of secure care placement continued to differ by gender when the nature of the mental health diagnosis was taken into account.

Conclusions

No definitive explanation is evident for the significantly different placement patterns of young men and young women with the same mental health diagnoses, but the anticipated consequences for some, young men and some young women are important. Proper explanation demands an examination of process variables outwith the remit of this study. The lack of routine scrutiny and transparent processes across secure settings could be responsible for the development of these differential placement practices; these practices seem at odds with the duty placed on public services by the Equality Act.
Tackling the global problem of traumatic stress in low-income countries: a pilot clinical trial comparing reconsolidation therapy to paroxetine in Nepal
Authors: Brunet Alain , Sapkota Ram P. , Guragain Bhushan , Tremblay Jacques , Saumier Daniel , Kirmayer Laurence J.
Published: September 2021

Background

Traumatic stress is a global mental health problem requiring novel, easily implemented treatment solutions. We compared the effectiveness and efficiency of Reconsolidation Therapy (RT) to the well-established antidepressant paroxetine, in reducing symptoms of traumatic stress among patients from Nepal, a low-income country.

Methods

Forty-six adults with posttraumatic stress disorder (PTSD) were randomized to one of two groups. The reconsolidation blocker propranolol was administered 90 min before briefly recalling a traumatic memory with a therapist, weekly for six consecutive weeks. This was compared to daily paroxetine for 26 weeks. Self-reported PTSD symptoms were assessed blindly at the 7th, 13th, and 26th weeks.

Results

An intent-to-treat analysis revealed a robust pre- to post-treatment main effect (β1 = − 4.83, 95% CI = [− 5.66, − 4.01], p < .001), whereby both groups improved, with Cohen’s effect sizes of d = 2.34 (95% CI = [1.57, 3.12]) for paroxetine, and of 2.82 (95% CI = [1.98, 3.66]) for RT after 7 weeks, suggesting treatment effectiveness for both groups in a real-world setting. Three and six-month follow-up yielded further significant improvement in both groups, which did not differ from each other.

Conclusion

RT also displayed promising efficiency, considering that it had been discontinued weeks earlier while the paroxetine treatment was continued, as recommended. RT could be taught in low-income countries as part of the local therapeutic resources to treat the core symptoms of PTSD, provided that such results are replicated on a broader scale.

Trial registration

ISRCTN34308454 (11/10/2017).
Systematically developing a family-based health promotion intervention for women with prior gestational diabetes based on evidence, theory and co-production: the Face-it study
Authors: Maindal Helle Terkildsen , Timm Anne , Dahl-Petersen Inger Katrine , Davidsen Emma , Hillersdal Line , Jensen Nanna Husted , Thøgersen Maja , Jensen Dorte Møller , Ovesen Per , Damm Peter , Kampmann Ulla , Vinter Christina Anne , Mathiesen Elisabeth Reinhardt , Nielsen Karoline Kragelund
Published: September 2021

Background

Women with prior gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes; however, this risk can be reduced by engaging in positive health behaviours e.g. healthy diet and regular physical activity. As such behaviours are difficult to obtain and maintain there is a need to develop sustainable behavioural interventions following GDM. We aimed to report the process of systematically developing a health promotion intervention to increase quality of life and reduce diabetes risk among women with prior GDM and their families. We distil general lessons about developing complex interventions through co-production and discuss our extensions to intervention development frameworks.

Methods

The development process draws on the Medical Research Council UK Development of complex interventions in primary care framework and an adaptation of a three-stage framework proposed by Hawkins et al. From May 2017 to May 2019, we iteratively developed the Face-it intervention in four stages: 1) Evidence review, qualitative research and stakeholder consultations; 2) Co-production of the intervention content; 3) Prototyping, feasibility- and pilot-testing and 4) Core outcome development. In all stages, we involved stakeholders from three study sites.

Results

During stage 1, we identified the target areas for health promotion in families where the mother had prior GDM, including applying a broad understanding of health and a multilevel and multi-determinant approach. We pinpointed municipal health visitors as deliverers and the potential of using digital technology. In stage 2, we tested intervention content and delivery methods. A health pedagogic dialogue tool and a digital health app were co-adapted as the main intervention components. In stage 3, the intervention content and delivery were further adapted in the local context of the three study sites. Suggestions for intervention manuals were refined to optimise flexibility, delivery, sequencing of activities and from this, specific training manuals were developed. Finally, at stage 4, all stakeholders were involved in developing realistic and relevant evaluation outcomes.

Conclusions

This comprehensive description of the development of the Face-it intervention provides an example of how to co-produce and prototype a complex intervention balancing evidence and local conditions. The thorough, four-stage development is expected to create ownership and feasibility among intervention participants, deliverers and local stakeholders.

Trial registration

ClinicalTrials.gov NCT03997773, registered retrospectively on 25 June 2019.
Role of the 2018 American Thyroid Association statement on postoperative hypoparathyroidism: a 5-year retrospective study
Authors: Qiu Yuxuan , Xing Zhichao , Fei Yuan , Qian Yuanfan , Luo Yan , Su Anping
Published: September 2021

Background

Definitions of postoperative hypoparathyroidism (hypoPT) have never reached consent until the American Thyroid Association (ATA) statement was released, with new characteristics and challenges.

Methods

Patients with papillary thyroid carcinoma who underwent primary total thyroidectomy between January 2013 and June 2018 were retrospectively enrolled. Symptoms of hypocalcemia and their frequency were stringently followed. Patients were divided into groups according to the ATA statement. Incidence of postoperative hypoPT and serum parathyroid hormone levels accompanied by calcium levels, from 1-day to at least 24-month follow-up.

Results

A total of 1749 patients were included: 458 (26.2%) had transient and 63 (3.6%) had permanent hypoPT. Transient hypoPT was found in 363 (20.7%) patients with biochemical hypoPT, 72 (4.1%) with clinical hypoPT, and 23 (1.3%) with relative hypoPT; permanent hypoPT was detected in 8 (0.5%) patients with biochemical hypoPT, 55 (3.1%) with clinical hypoPT, and none with relative hypoPT. Female sex, age ≥ 55 years, unintentional parathyroid gland resection, and autotransplantation of ≥ 2 parathyroid glands were independent risk factors for transient biochemical hypoPT. Age ≥ 55 years, bilateral central neck dissection, and isthmus tumor location were independent risk factors for transient clinical hypoPT. A postoperative 1-day percentage of parathyroid hormone (PTH) reduction of > 51.1% was an independent risk factor for relative hypoPT (odds ratio, 4.892; 95% confidence interval, 1.653–14.480;P = 0.004). No independent risk factor for permanent hypoPT was found.

Conclusion

ATA diagnostic criteria for postoperative hypoPT are of great value in differentiating patients by hypocalcemia symptoms and choosing corresponding clinical assistance; however, they may underestimate the actual incidence.
Rash and cholestatic liver injury caused by methimazole in a woman with Turner syndrome and Graves’s disease: a case report and literature review
Authors: Zeng Jinhui , Luo Fangtao , Lin Zhihua , Chen Yinghong , Wang Xiaoyun , Song Yuanhao
Published: September 2021

Background

Rash and cholestatic liver injury caused by methimazole (MMI) in patients with Turner syndrome (TS) and Graves’s disease (GD) are rarely reported, and there is a paucity of reports on the management of this condition. It is not clear whether propylthiouracil (PTU) can be used as a safe alternative in this case.

Case presentation:

A 37-year-old woman was admitted to our hospital with rash, severe pruritus and a change in urine colour after 2 months of GD treatment with MMI. Physical examination showed rash scattered over the limbs and torso, mild jaundice of the sclera and skin, short stature, facial moles, immature external genitals and diffuse thyroid gland enlargement. Liver function tests indicated an increase in total bilirubin, direct bilirubin, total bile acid, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase and alkaline phosphatase. The level of sex hormones suggested female hypergonadotropic hypogonadism. The karyotype of peripheral blood was 46, X, i(X)(q10)/45, X. After excluding biliary obstruction and other common causes of liver injury, combined with rash and abnormal liver function following oral administration of MMI, the patient was diagnosed as having TS with GD and rash and cholestatic liver injury caused by MMI. MMI was immediately discontinued, and eleven days after treatment with antihistamine and hepatoprotective agents was initiated, the rash subsided, and liver function returned to nearly normal. Because the patient did not consent to administration of 131I or thyroid surgery, hyperthyroidism was successfully controlled with PTU. No adverse drug reactions were observed after switching to PTU.

Conclusions

While patients with TS and GD are undergoing treatment with MMI, their clinical manifestations, liver functions, and other routine blood test results should be closely monitored. When patients with TS and GD manifest adverse reactions to MMI such as rash and cholestatic liver injury, it is necessary to discontinue MMI and treat with antihistamine and hepatoprotective agents. After the rash subsides and liver function returns to nearly normal, PTU can effectively control hyperthyroidism without adverse drug reactions.
Administration of hydro-alcoholic extract of spinach improves oxidative stress and inflammation in high-fat diet-induced NAFLD rats
Authors: Amirinejad Ali , Totmaj Ali Saneei , Mardali Farzaneh , Hekmatdoost Azita , Emamat Hadi , Safa Majid , Shidfar Farzad
Published: September 2021

Background

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The aim of this study was to evaluate the effects of hydro-alcoholic extract of spinach (HES) on hepatic and serum measurements of NAFLD in a rat model.

Methods

In the prevention phase, 18 Sprague–Dawley rats were fed a high-fat diet, a high-fat diet plus 400 mg/kg HES, or a chow diet for seven weeks. For the treatment phase, after the induction of NAFLD, they were fed a high-fat diet, a high-fat diet plus 400 mg/kg HES, a chow diet, or a chow diet plus 400 mg/kg HES for four weeks (n = 6).

Results

Administration of HES combined with high-fat diet in rats was associated with decreased food intake (P < 0.01), weight loss (P = 0.01), and increased superoxide dismutase (SOD) (P = 0.02) enzyme activity in the liver, at the end of the prevention phase. hs-CRP (P < 0.05), PTX-3 (P < 0.05), and TNF-α (P < 0.05) gene expression in the liver were decreased and PPAR-γ (P < 0.05) gene expression in the liver was increased by spinach intake, both in the prevention and treatment phases. Furthermore, administration of spinach in the treatment phase increased serum TAC (P = 0.03) and hepatic GPX (P = 0.01) enzyme activity.

Conclusion

Taking into account the potential beneficial effects of HES on prevention and treatment of NAFLD in the present study, to confirm these findings, we propose that further clinical trials be conducted on human subjects with NAFLD.
The impact of a faculty development program, the Leadership in Academic Medicine Program (LAMP), on self-efficacy, academic promotion and institutional retention
Authors: Tung Judy , Nahid Musarrat , Rajan Mangala , Logio Lia
Published: September 2021

Background

Academic medical centers invest considerably in faculty development efforts to support the career success and promotion of their faculty, and to minimize faculty attrition. This study evaluated the impact of a faculty development program called the Leadership in Academic Medicine Program (LAMP) on participants’ (1) self-ratings of efficacy, (2) promotion in academic rank, and (3) institutional retention.

Method

Participants from the 2013–2020 LAMP cohorts were surveyed pre and post program to assess their level of agreement with statements that spanned domains of self-awareness, self-efficacy, satisfaction with work and work environment. Pre and post responses were compared using McNemar’s tests. Changes in scores across gender were compared using Wilcoxon Rank Sum/Mann-Whitney tests.

LAMP participants were matched to nonparticipant controls by gender, rank, department, and time of hire to compare promotions in academic rank and departures from the organization. Kaplan Meier curves and Cox proportional hazards models were used to examine differences.

Results

There were significant improvements in almost all self-ratings on program surveys (p < 0.05). Greatest improvements were seen in “understand the promotions process” (36% vs. 94%), “comfortable negotiating” (35% vs. 74%), and “time management” (55% vs. 92%). There were no statistically significant differences in improvements by gender, however women faculty rated themselves lower on all pre-program items compared to men.

There was significant difference found in time-to-next promotion (p = 0.003) between LAMP participants and controls. Kaplan-Meier analysis demonstrated that LAMP faculty achieved next promotion more often and faster than controls. Cox-proportional-hazards analyses found that LAMP faculty were 61% more likely to be promoted than controls (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.16–2.23, p-value = 0.004).

There was significant difference found in time-to-departure (p < 0.0001) with LAMP faculty retained more often and for longer periods. LAMP faculty were 77% less likely to leave compared to controls (HR 0.23, 95% CI 0.16–0.34, p < 0.0001).

Conclusions

LAMP is an effective faculty development program as measured subjectively by participant self-ratings and objectively through comparative improvements in academic promotions and institutional retention.
Middle-aged and elderly users’ continuous usage intention of health maintenance-oriented WeChat official accounts: empirical study based on a hybrid model in China
Authors: Xu Lin , Li Pengfei , Hou Xiaorong , Yu Hongfan , Tang Tingting , Liu Ting , Xiang Shoushu , Wu Xiaoqian , Huang Cheng
Published: September 2021

Background

Although middle-aged and elderly users are the main group targeted by health maintenance-oriented WeChat official accounts (HM-WOAs), few studies have explored the relationship of these accounts and their users. Exploring the factors that influence the continuous adoption of WOAs is helpful to strengthen the health education of middle-aged and elderly individuals.

Objective

We developed a new theoretical model and explored the factors that influence middle-aged and elderly individuals' continuous usage intention for HM-WOA. Performance expectancy mediated the effects of the model in explaining continuous usage intention and introduced health literacy into the model.

Methods

We established a hybrid theoretical model on the basis of the unified theory of acceptance and use of technology 2 model (UTAUT2), the health belief model (BHM), protection motivation theory (PMT), and health literacy. We collected valid responses from 396 middle-aged and elderly users aged ≥ 45 years in China. To verify our hypotheses, we analyzed the data using structural equation modeling.

Results

Performance expectancy (β = 0.383,P < 0.001), hedonic motivation (β = 0.502,P < 0.001), social influence (β = 0.134,P = 0.049), and threat appraisal (β = 0.136,P < 0.001) positively influenced middle-aged and elderly users' continuous usage intention. Perceived health threat (β =  − 0.065,P = 0.053) did not have a significant effect on continuous usage intention. Both threat appraisal (β = 0.579,P < 0.001) and health literacy (β = 0.579,P < 0.001) positively affected performance expectancy. Threat appraisal indirectly affected continuous usage intention through performance expectancy mediation.

Conclusions

Our new theoretical model is useful for understanding middle-aged and elderly users' continuous usage intention for HM-WOA. Performance expectancy plays a mediation role between threat appraisal and continuous usage intention, and health literacy positively affects performance expectancy.
Considerations of Australian community pharmacists in the provision and implementation of cognitive pharmacy services: a qualitative study
Authors: Yong Faith R. , Hor Su-Yin , Bajorek Beata V.
Published: September 2021

Background

Australian federally-funded cognitive pharmacy services (CPS) (e.g. medication management and reconciliation services) have not been translated into practice consistently. These health services are purportedly accessible across all Australian community pharmacies, yet are not delivered as often as pharmacists would like. There are international indicators that pharmacists lack the complete behavioural control required to prioritise CPS, despite their desire to deliver them. This requires local investigation.

Objective

To explore Australian pharmacists’ perspectives [1] as CPS providers on the micro level, and [2] on associated meso and macro level CPS implementation issues.

Methods

Registered Australian community pharmacists were recruited via professional organisations and snowball sampling. Data were collected via an online demographic survey and semi-structured interviews until data saturation was reached. Interview transcripts were de-identified then verified by participants. Content analysis was performed to identify provider perspectives on the micro level. Framework analysis using RE-AIM was used to explore meso and macro implementation issues.

Results

Twenty-three participants across Australia gave perspectives on CPS provision. At the micro level, pharmacists did not agree on a single definition of CPS. However, they reported complexity in interactional work and patient considerations, and individual pharmacist factors that affected them when deciding whether to provide CPS. There was an overall deficiency in pharmacy workplace resources reported to be available for implementation and innovation. Use of an implementation evaluation framework suggested CPS implementation is lacking sufficient structural support, whilst reach into target population, service consistency and maintenance for CPS were not specifically considered by pharmacists.

Conclusions

This analysis of pharmacist CPS perspectives suggests slow uptake may be due to a lack of evidence-based, focused, multi-level implementation strategies that take ongoing pharmacist role transition into account. Sustained change may require external change management and implementation support, engagement of frontline clinicians in research, and the development of appropriate pharmacist practice models to support community pharmacists in their CPS roles.

Trial registration

This study was not a clinical intervention trial. It was approved by the University of Technology Sydney Human Research Ethics Committee (UTS HREC 19–3417) on the 26th of April 2019.
Perceptions of underlying practice hierarchies: Who is managing my care?
Authors: Officer Tara N , McBride-Henry Karen
Published: September 2021

Background

The introduction of new health professional roles, such as that of the nurse practitioner and pharmacist prescriber in primary health care can lead to changes in health service delivery. Consumers, having used these roles, often report high satisfaction. However, there is limited knowledge of how these individuals position nurse practitioner and pharmacist prescriber roles within existing practice structures.

Methods

Semi-structured interviews were conducted with 21 individuals receiving services from these practitioners in New Zealand primary health care. Interviews were recorded and transcribed verbatim for thematic analysis.

Results

Participant views reflect established practice hierarchies, placing advanced practitioners ‘below’ general practitioners. Participants are unable to articulate what it was about these practitioners that meant they operated at lower tiers and often considered practitioners to act as ‘their doctor’. They also highlight structural barriers impairing the ability of these providers to operate within their full scope of practice.

Conclusions

While seeing value in the services they receive, consumers are often unable to position nurse practitioner and pharmacist prescriber roles within health system contexts or to articulate how they value their practitioner’s skills. Embedded structural barriers may be more visible to consumers than their interactions with the health system suggest. This may influence peoples’ ability to receive intended or optimal health services. Consumer ‘health professional literacy’ around the functions of distinct health practitioners should be supported so that they may make informed service provision choices.
The ATPase SRCAP is associated with the mitotic apparatus, uncovering novel molecular aspects of Floating-Harbor syndrome
Authors: Messina Giovanni , Prozzillo Yuri , Delle Monache Francesca , Santopietro Maria Virginia , Atterrato Maria Teresa , Dimitri Patrizio
Published: September 2021

Background

A variety of human genetic diseases is known to be caused by mutations in genes encoding chromatin factors and epigenetic regulators, such as DNA or histone modifying enzymes and members of ATP-dependent chromatin remodeling complexes. Floating-Harbor syndrome is a rare genetic disease affecting human development caused by dominant truncating mutations in the SRCAP gene, which encodes the ATPase SRCAP, the core catalytic subunit of the homonymous chromatin-remodeling complex. The main function of the SRCAP complex is to promote the exchange of histone H2A with the H2A.Z variant. According to the canonical role played by the SRCAP protein in epigenetic regulation, the Floating-Harbor syndrome is thought to be a consequence of chromatin perturbations. However, additional potential physiological functions of SRCAP have not been sufficiently explored.

Results

We combined cell biology, reverse genetics, and biochemical approaches to study the subcellular localization of the SRCAP protein and assess its involvement in cell cycle progression in HeLa cells. Surprisingly, we found that SRCAP associates with components of the mitotic apparatus (centrosomes, spindle, midbody), interacts with a plethora of cytokinesis regulators, and positively regulates their recruitment to the midbody. Remarkably, SRCAP depletion perturbs both mitosis and cytokinesis. Similarly, DOM-A, the functional SRCAP orthologue in Drosophila melanogaster, is found at centrosomes and the midbody in Drosophila cells, and its depletion similarly affects both mitosis and cytokinesis.

Conclusions

Our findings provide first evidence suggesting that SRCAP plays previously undetected and evolutionarily conserved roles in cell division, independent of its functions in chromatin regulation. SRCAP may participate in two different steps of cell division: by ensuring proper chromosome segregation during mitosis and midbody function during cytokinesis. Moreover, our findings emphasize a surprising scenario whereby alterations in cell division produced by SRCAP mutations may contribute to the onset of Floating-Harbor syndrome.
RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance
Authors: McCaffrey Timothy A. , Toma Ian , Yang Zhaoquing , Katz Richard , Reiner Jonathan , Mazhari Ramesh , Shah Palak , Tackett Michael , Jones Dan , Jepson Tisha , Falk Zachary , Wargodsky Richard , Shtakalo Dmitry , Antonets Denis , Ertle Justin , Kim Ju H. , Lai Yinglei , Arslan Zeynep , Aledort Emily , Alfaraidy Maha , Laurent Georges St.
Published: September 2021

Background

Cardiovascular disease had a global prevalence of 523 million cases and 18.6 million deaths in 2019. The current standard for diagnosing coronary artery disease (CAD) is coronary angiography. Surprisingly, despite well-established clinical indications, up to 40% of the one million invasive cardiac catheterizations return a result of ‘no blockage’. The present studies employed RNA sequencing of whole blood to identify an RNA signature in patients with angiographically confirmed CAD.

Methods

Whole blood RNA was depleted of ribosomal RNA (rRNA) and analyzed by single-molecule sequencing of RNA (RNAseq) to identifytranscriptsassociated withCAD (TRACs) in a discovery group of 96 patients presenting for elective coronary catheterization. The resulting transcript counts were compared between groups to identify differentially expressed genes (DEGs).

Results

Surprisingly, 98% of DEGs/TRACs were down-regulated ~ 1.7-fold in patients with mild to severe CAD (> 20% stenosis). The TRACs were independent of comorbid risk factors for CAD, such as sex, hypertension, and smoking. Bioinformatic analysis identified an enrichment in transcripts such as FoxP1, ICOSLG, IKZF4/Eos, SMYD3, TRIM28, and TCF3/E2A that are likely markers of regulatory T cells (Treg), consistent with known reductions in Tregs in CAD. A validation cohort of 80 patients confirmed the overall pattern (92% down-regulation) and supported many of the Treg-related changes. TRACs were enriched for transcripts associated with stress granules, which sequester RNAs, and ciliary and synaptic transcripts, possibly consistent with changes in the immune synapse of developing T cells.

Conclusions

These studies identify a novel mRNA signature of a Treg-like defect in CAD patients and provides a blueprint for a diagnostic test for CAD. The pattern of changes is consistent with stress-related changes in the maturation of T and Treg cells, possibly due to changes in the immune synapse.
Small extrachromosomal circular DNA (eccDNA): major functions in evolution and cancer
Authors: Ling Xiaoxuan , Han Yali , Meng Jinxue , Zhong Bohuan , Chen Jialong , Zhang He , Qin Jiheng , Pang Jing , Liu Linhua
Published: September 2021

Extrachromosomal circular DNA (eccDNA) refers to a type of circular DNA that originate from but are likely independent of chromosomes. Due to technological advancements, eccDNAs have recently emerged as multifunctional molecules with numerous characteristics. The unique topological structure and genetic characteristics of eccDNAs shed new light on the monitoring, early diagnosis, treatment, and prediction of cancer. EccDNAs are commonly observed in both normal and cancer cells and function via different mechanisms in the stress response to exogenous and endogenous stimuli, aging, and carcinogenesis and in drug resistance during cancer treatment. The structural diversity of eccDNAs contributes to the function and numerical diversity of eccDNAs and thereby endows eccDNAs with powerful roles in evolution and in cancer initiation and progression by driving genetic plasticity and heterogeneity from extrachromosomal sites, which has been an ignored function in evolution in recent decades. EccDNAs show great potential in cancer, and we summarize the features, biogenesis, evaluated functions, functional mechanisms, related methods, and clinical utility of eccDNAs with a focus on their role in evolution and cancer.
Pedunculated early colorectal cancer with nodal metastasis: a case report
Authors: Kondo Hiroka , Ogawa Shimpei , Ohki Takeshi , Bamba Yoshiko , Kaneko Yuka , Koshino Kurodo , Nakagawa Ryosuke , Tani Kimitaka , Maeda Fumi , Aihara Hisako , Tokito Fumiaki , Fujikawa Shuji , Yamamoto Tomoko , Nagashima Yoji , Inoue Yuji , Itabashi Michio , Yamaguchi Shigeki
Published: September 2021

Background

Pedunculated polyps are more likely to be amenable to complete resection than non-pedunculated early colorectal cancers and rarely require additional surgery. We encountered a patient with a pedunculated early colorectal cancer that consisted of poorly differentiated adenocarcinoma with lymphatic invasion. We performed an additional bowel resection and found nodal metastasis.

Case presentation

A 43-year-old woman underwent colonoscopy after a positive fecal occult blood test. The colonoscopist found a 20-mm pedunculated polyp in the descending colon and performed endoscopic resection. Histopathologic examination revealed non-solid type poorly differentiated adenocarcinoma. The lesion invaded the submucosa (3500 μm from the muscularis mucosa) and demonstrated lymphatic invasion. In spite of the early stage of this cancer, the patient was considered at high risk for nodal metastasis. She was referred to our institution, where she underwent bowel resection. Although there was no residual cancer after her endoscopic resection, a metastatic lesion was found in one regional lymph node. The patient is undergoing postoperative adjuvant chemotherapy, and there has been no evidence of recurrence 3 months after the second surgery.

Conclusions

Additional bowel resection is indicated for patients with pedunculated polyps and multiple risk factors for nodal metastasis, such as poorly differentiated adenocarcinoma and lymphatic invasion. We encountered just such a patient who did have a nodal metastasis; herein, we report her case history with a review of the literature.
Physiotherapy services in patient care in Bhutan
Authors: Tamang Monu , Dorji Thinley
Published: September 2021

Physiotherapy and rehabilitative services are an integral part of patient care, but in many developing countries they are not considered a priority and are either not available or not easily accessible to those who need them. Bhutan is one such country where healthcare is provided free of cost to all, but as of 2021 physiotherapy services were available only in 26 of 48 hospitals and 19 of 20 districts. The number of physiotherapy professionals per 10,000 population is 1.4 with significant rates of attrition. There is lack of awareness among patients and other health professionals about physiotherapy and rehabilitation services. The country needs to integrate physiotherapy and rehabilitation services into the overall health policy framework and develop proper planning of human resources and infrastructure to meet the current and future demands.
A cross-sectional analysis of persistent low back pain, using correlations between lumbar stiffness, pressure pain threshold, and heat pain threshold
Authors: Nim Casper Glissmann , O’Neill Søren , Geltoft Anne Gellert , Jensen Line Korsholm , Schiøttz-Christensen Berit , Kawchuk Gregory Neil
Published: September 2021

Introduction

Little is known about the underlying biomechanical cause of low back pain (LBP). Recently, technological advances have made it possible to quantify biomechanical and neurophysiological measurements, potentially relevant factors in understanding LBP etiology. However, few studies have explored the relation between these factors. This study aims to quantify the correlation between biomechanical and neurophysiological outcomes in non-specific LBP and examine whether these correlations differ when considered regionally vs. segmentally.

Methods

This is a secondary cross-sectional analysis of 132 participants with persistent non-specific LBP. Biomechanical data included spinal stiffness (global stiffness) measured by a rolling indenter. Neurophysiological data included pain sensitivity (pressure pain threshold and heat pain threshold) measured by a pressure algometer and a thermode. Correlations were tested using Pearson’s product-moment correlation or Spearman’s rank correlation as appropriate. The association between these outcomes and the segmental level was tested using ANOVA with post-hoc Tukey corrected comparisons.

Results

A moderate positive correlation was found between spinal stiffness and pressure pain threshold, i.e., high degrees of stiffness were associated with high pressure pain thresholds. The correlation between spinal stiffness and heat pain threshold was poor and not statistically significant. Aside from a statistically significant minor association between the lower and the upper lumbar segments and stiffness, no other segmental relation was shown.

Conclusions

The moderate correlation between spinal stiffness and mechanical pain sensitivity was the opposite of expected, meaning higher degrees of stiffness was associated with higher pressure pain thresholds. No clinically relevant segmental association existed.
Influences of cold atmospheric plasma on apoptosis related molecules in osteoblast-like cells in vitro
Authors: Eggers Benedikt , Marciniak Jana , Memmert Svenja , Wagner Gunar , Deschner James , Kramer Franz-Josef , Nokhbehsaim Marjan
Published: September 2021

Background

Cold atmospheric plasma (CAP) has recently been identified as a novel therapeutic strategy for supporting processes of wound healing. Since CAP is additionally known to kill malignant cells, our study intends to determine the influence of CAP on crucial molecules involved in the molecular mechanism of apoptosis in osteoblast-like cells.

Methods

Human osteoblast-like cells were CAP-treated for 30 and 60 s. CAP effects on critical factors related to apoptosis were studied at transcriptional and protein level using real time-PCR, immunofluorescence staining and western blot. Phalloidin / DAPI staining was used for analyzing the cell morphology. In addition, apoptotic outcomes of CAP were displayed using flow cytometry analysis. For studying intracellular signaling pathways, MAP kinase MEK 1/2 and PI3K were blocked. Finally, the effects of CAP on caspase-3 activity were examined using a caspase-3 assay.

Results

CAP treatment resulted in a significant downregulation of p53 and apoptotic protease activating factor (APAF)-1, caspase (CASP)9, CASP3, BCL2 Antagonist/Killer (BAK)1, and B-Cell Lymphoma (BCL)2 mRNA expression at 1 d. An inhibitory effect of CAP on apoptotic genes was also shown under inflammatory and apoptotic conditions. Nuclear translocation of p53 was determined in CAP treated cells at the early and late stage, after 15 min, 30 min, and 1 h. p53 and APAF-1 protein levels were reduced at 1 d, visualized by immunofluorescence and western blot, respectively. Moreover, a morphological cytoskeleton modification was observed after CAP treatment at 1 d. Further, both CAP-treated and untreated (control) cells remained equally vital as detected by flow cytometry analysis. Interestingly, CAP-associated downregulation of CASP9 and CASP3 mRNA gene expression was also visible after blocking MAP kinase and PI3K. Finally, CAP led to a decrease in CASP3 activity in osteoblast-like cells under normal and apoptotic conditions.

Conclusions

Our in vitro-study demonstrated, that CAP decreases apoptosis related molecules in osteoblast-like cells, underlining a beneficial effect on hard-tissue cells.
Increased risk of chronic fatigue and hair loss following COVID-19 in individuals with hypohidrotic ectodermal dysplasia
Authors: Hennig Verena , Schuh Wolfgang , Neubert Antje , Mielenz Dirk , Jäck Hans-Martin , Schneider Holm
Published: September 2021

Background

Hypohidrotic ectodermal dysplasia (HED) is a group of genodermatoses in which deficient ectodysplasin A signalling leads to maldevelopment of skin appendages, various eccrine glands, and teeth. Individuals with HED often have disrupted epithelial barriers and, therefore, were suspected to be more susceptible to coronavirus infection.

Methods

56 households with at least one member who had coronavirus disease of 2019 (COVID-19) were enrolled in a longitudinal study to compare the course of illness, immune responses, and long-term consequences of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection in HED patients (n = 15, age 9–52 years) and control subjects of the same age group (n = 149).

Results

In 14 HED patients, mild or moderate typical COVID-19 symptoms were observed that lasted for 4–45 days. Fever during the first days sometimes required external cooling measures. The course of COVID-19 was similar to that in control subjects if patients developed antibodies blocking the SARS-CoV-2 spike protein. Five out of six HED patients with completely abrogated ectodysplasin A signalling (83%) suffered from chronic, in two cases very severe fatigue following COVID-19, while only 25% of HED patients with residual activity of this pathway and 21% of control subjects recovering from COVID-19 experienced postinfectious fatigue. Hair loss after COVID-19 was also more frequent among HED patients (64%) than in the control group (13%).

Conclusions

HED appears to be associated with an increased risk of long-term consequences of a SARS-CoV-2 infection. Preventive vaccination against COVID-19 should be recommended for individuals affected by this rare genetic disorder.
Knowledge and acceptance of HPV vaccination and its associated factors among parents of daughters in Addis Ababa, Ethiopia: a community-based cross-sectional study
Authors: Dereje Nebiyu , Ashenafi Abigia , Abera Anteneh , Melaku Efrata , Yirgashewa Kaleb , Yitna Meron , Shewaye Sarona , Fasil Tsedenia , Yoseph Yadel
Published: September 2021

Background

Cervical cancer is one of the most diagnosed and deadly cancers in women globally. Though vaccination is an effective way to reduce cervical cancer, people’s knowledge and acceptance of the vaccination remains a challenge in low and middle-income countries. Therefore, the aim of this study was to assess the level of knowledge and acceptance of Human Papilloma Virus (HPV) vaccination and its associated factors among parents of daughters in Addis Ababa, Ethiopia.

Methods

A community-based cross-sectional study was conducted among parents or guardians whose daughters are in the age group of 9–17 years and residing in Akaki-Kalty sub-city in Addis Ababa. A multistage sampling technique was used to select the study participants (n = 430). Face-to-face interview was conducted by using a structured questionnaire. Factors associated with the acceptance of HPV vaccination was identified by multivariable binary logistic regression and expressed by adjusted odds ratio (aOR), and respective 95% confidence interval.

Results

Complete response was obtained from 422 (98.1%) of the participants and their mean age was 39.0 years (SD ± 9.9). Out of the study participants, 41.7% and 72.0% had poor knowledge on cervical cancer and HPV, respectively. More than a quarter (27.0%) of the participants has never heard about HPV vaccine. One-third (36.5%) of the participants had negative attitude towards the HPV vaccine. Overall, 94.3% of the study participants were willing to vaccinate their daughters for HPV. Vaccine acceptability was associated with higher monthly income (aOR = 2.48, 95% CI 1.08–6.34), good knowledge on HPV (aOR = 2.32, 95% CI 1.56–4.87) and the vaccine (aOR = 2.24, 95% CI 1.12–8.60), and positive attitude towards the vaccine (aOR = 5.03, 95% CI 1.63—9.56).

Conclusions

The overall HPV vaccine acceptance was high. However, two out of five and one-thirds of the parents had poor knowledge on cervical cancer and negative attitude towards the HPV vaccine, respectively. Higher monthly income, good knowledge on HPV and the vaccine, and positive attitude towards the vaccine were associated with acceptance of HPV vaccination. To ensure sustainable acceptance of HPV vaccination, it is crucial to increase the community awareness in a sustainable manner.
LeafGo: Leaf to Genome, a quick workflow to produce high-quality de novo plant genomes using long-read sequencing technology
Authors: Driguez Patrick , Bougouffa Salim , Carty Karen , Putra Alexander , Jabbari Kamel , Reddy Muppala , Soppe Richard , Cheung Ming Sin , Fukasawa Yoshinori , Ermini Luca
Published: September 2021

Currently, different sequencing platforms are used to generate plant genomes and no workflow has been properly developed to optimize time, cost, and assembly quality. We present LeafGo, a complete de novo plant genome workflow, that starts from tissue and produces genomes with modest laboratory and bioinformatic resources in approximately 7 days and using one long-read sequencing technology. LeafGo is optimized with ten different plant species, three of which are used to generate high-quality chromosome-level assemblies without any scaffolding technologies. Finally, we report the diploid genomes ofEucalyptus rudisandE. camaldulensisand the allotetraploid genome ofArachis hypogaea.
Identification of anti-horn fly vaccine antigen candidates using a reverse vaccinology approach
Authors: Domingues Luísa N. , Bendele Kylie G. , Halos Lénaïg , Moreno Yovany , Epe Christian , Figueiredo Monica , Liebstein Martin , Guerrero Felix D.
Published: September 2021

Background

The horn fly,Haematobia irritans irritans, causes significant production losses to the cattle industry. Horn fly control relies on insecticides; however, alternative control methods such as vaccines are needed due to the fly's capacity to quickly develop resistance to insecticides, and the pressure for eco-friendly options.

Methods

We used a reverse vaccinology approach comprising three vaccine prediction and 11 annotation tools to evaluate and rank 79,542 translated open reading frames (ORFs) from the horn fly's transcriptome, and selected 10 transcript ORFs as vaccine candidates for expression inPichia pastoris. The expression of the 10 selected transcripts and the proteins that they encoded were investigated in adult flies by reverse transcription polymerase chain reaction (RT-PCR) and mass spectrometry, respectively. Then, we evaluated the immunogenicity of a vaccine candidate in an immunization trial and the antigen’s effects on horn fly mortality and fecundity in an in vitro feeding assay.

Results

Six of the ten vaccine candidate antigens were successfully expressed inP. pastoris. RT-PCR confirmed the expression of all six ORFs in adult fly RNA. One of the vaccine candidate antigens, BI-HS009, was expressed in sufficient quantity for immunogenicity and efficacy trials. The IgG titers of animals vaccinated with BI-HS009 plus adjuvant were significantly higher than those of animals vaccinated with buffer plus adjuvant only from days 42 to 112, with a peak on day 56. Progeny of horn flies feeding upon blood from animals vaccinated with BI-HS009 plus adjuvant collected on day 56 had 63% lower pupariation rate and 57% lower adult emergence than the control group (ANOVA:F(1, 6) = 8.221,P = 0.028 andF(1, 6) = 8.299,P = 0.028, respectively).

Conclusions

The reverse vaccinology approach streamlined the discovery process by prioritizing possible vaccine antigen candidates. Through a thoughtful process of selection and in vivo and in vitro evaluations, we were able to identify a promising antigen for an anti-horn fly vaccine.

Graphical abstract