bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-223-3p downregulates the inflammatory response in preeclampsia placenta via targeting NLRP3
Authors: Liu Xueqiong , Li Zhiyue , Lu Dan
Published: March 2024

Objective

To investigate the regulatory role of miR-223-3p in the inflammatory response of PE placenta.

Methods

PE and normal placental tissues were collected to measure the expression of NLRP3 and miR-223-3p. The targeting relationship between NLRP3 and miR-223-3P was verified by bioinformatics analysis and classical double-luciferase reporter gene assay. Lipopolysaccharide (LPS) was used to induce HTR8/SVneo cells as PE placental cell inflammation model. Then we transfected miR-223-3p overexpression/miR-223-3p negative control plasmid into the LPS-induced HTR8/SVneo cells. Next, the expressions of NLRP3, Caspase-1, GSDMD, IL-1β and IL-18 were evaluated to elucidate the regulatory effect of miR-223-3p on the inflammatory response mediated by NLRP3 in PE placenta.

Results

Compared with normal controls, NLRP3 was significantly up-regulated in PE placenta, while miR-223-3p was down-regulated. In addition, NLRP3 was a direct target of miR-223-3p. Further research revealed that the expression of NLRP3, Caspase-1, GSDMD, IL-1β and IL-18 could be obviously promoted in HTR8/SVneo cells treated with LPS (500 ng/ml) for 24 h, nevertheless it could be significantly suppressesed under the overexpression of miR-223-3p.

Conclusion

MiR-223-3p suppressed NLRP3 inflamariomes activation, downstream inflammatory factors secretion and pyroptosis in LPS-induced HTR8/SVneo cells indicating that miR-223-3p could serve as an anti-inflammatory factor in preeclampsia.
Prediction of the efficacy of group cognitive behavioral therapy using heart rate variability based smart wearable devices: a randomized controlled study
Authors: Lin Zexin , Zheng Junjie , Wang Yang , Su Zhao , Zhu Rongxin , Liu Rongxun , Wei Yange , Zhang Xizhe , Wang Fei
Published: March 2024

Background

Depression and anxiety are common and disabling mental health problems in children and young adults. Group cognitive behavioral therapy (GCBT) is considered that an efficient and effective treatment for these significant public health concerns, but not all participants respond equally well. The aim of this study was to examine the predictive ability of heart rate variability (HRV), based on sensor data from consumer-grade wearable devices to detect GCBT effectiveness in early intervention.

Methods

In a study of 33 college students with depression and anxiety, participants were randomly assigned to either GCBT group or a wait-list control (WLC) group. They wore smart wearable devices to measure their physiological activities and signals in daily life. The HRV parameters were calculated and compared between the groups. The study also assessed correlations between participants’ symptoms, HRV, and GCBT outcomes.

Results

The study showed that participants in GCBT had significant improvement in depression and anxiety symptoms after four weeks. Higher HRV was associated with greater improvement in depressive and anxious symptoms following GCBT. Additionally, HRV played a noteworthy role in determining how effective GCBT was in improve anxiety(P = 0.002) and depression(P = 0.020), and its predictive power remained significant even when considering other factors.

Conclusion

HRV may be a useful predictor of GCBT treatment efficacy. Identifying predictors of treatment response can help personalize treatment and improve outcomes for individuals with depression and anxiety.

Trial registration

The trial has been retrospectively registered on [22/06/2023] with the registration number [NCT05913349] in the ClinicalTrials.gov.

Condensed abstract

Variations in heart rate variability (HRV) have been associated with depression and anxiety, but the relationship of baseline HRV to treatment outcome in depression and anxiety is unclear. This study predicted GCBT effectiveness using HRV measured by wearable devices. 33 students with depression and anxiety participated in a trial comparing GCBT and wait-list control. HRV parameters from wearables correlated with symptoms (PHQ, PSS) and GCBT effectiveness. Baseline HRV levels are strongly associated with GCBT treatment outcomes. HRV may serve as a useful predictor of efficacy of GCBT treatment,facilitating personalized treatment approaches for individuals with depression and anxiety.
An online survey capturing the views of stakeholders on primary school food systems across the four UK nations
Authors: Spence S. , McSweeney L. , Woodside J. V. , Schliemann D. ,   on behalf of the GENIUS Network
Published: March 2024

Background

In 2020, the Generating Excellent Nutrition in UK Schools (GENIUS) Network was established to develop an understanding of the school food system across the four UK nations. This study explores stakeholders’ views (headteachers, teachers, parents and pupils) on what works well, the challenges, and what an ideal primary school food system includes.

Methods

An online ‘School Food Survey’ was created in Qualtrics XM including closed and open-ended questions about the primary school food system. The Qualtrics link was distributed to stakeholders with an interest in school food through key contacts and networks across the four UK nations (21st June to 21st July and September 2021). Responses from the open-ended questions were exported from Qualtrics into Excel and analysed using SPSS. Aspects of qualitative content analysis were applied to summarise, code and quantify responses. Identified codes were entered by stakeholder, for example, parents and their response to the question into a Matrix table to allow identification of categories, themes and interpretation.

Results

A total of 509 participants completed the survey: most participants were from Scotland (n = 281; 55%) and England (n = 213; 42%) and were parents (n = 394). There were some consistent views across stakeholder responses, for example, the range of healthy options, costs, and portion sizes offered to pupils. Parents views varied, with some expressing the range of healthy options worked well and others reporting too many unhealthy choices. The cost of school food and school food funding presented challenges for both parents and schools. For parents, an ideal school food system would include a wide variety of fresh healthy food choices that were made on site, use quality produce, be inclusive for all cultures and diets, and provide food portion sizes appropriate for pupils ages.

Conclusions

The findings iterate the diversity and some inconsistencies between stakeholders, emphasising the complexity and competing tensions school food systems encounter. Parental involvement and consideration of school-level and national factors are important when identifying challenges, what works well and describing an ideal primary school food system.
Development, scoring, and reliability for the Microscale Audit of Pedestrian Streetscapes for Safe Routes to School (MAPS-SRTS) instrument
Authors: Ganzar Leigh Ann , Burford Katie , Salvo Deborah , Spoon Chad , Sallis James F. , Hoelscher Deanna M.
Published: March 2024

Background

Active commuting to school can be a meaningful contributor to overall physical activity in children. To inform better micro-level urban design near schools that can support active commuting to school, there is a need for measures that capture these elements. This paper describes the adaptation of an observational instrument for use in assessing micro-scale environments around urban elementary schools in the United States.

Methods

The Micro-scale Audit of Pedestrian Streetscapes for Safe Routes to School (MAPS-SRTS) was developed from existing audit instruments not designed for school travel environments and modifications for the MAPS-SRTS instrument include the structure of the audit tool sections, the content, the observation route, and addition of new subscales. Subscales were analyzed for inter-rater reliability in a sample of 36 schools in Austin, TX. To assess reliability for each subscale, one-way random effects single-measure intraclass correlation coefficients (ICC) were used.

Results

Compared to the 30 original subscales, the adapted MAPS-SRTS included 26 (86.6%) subscales with revised scoring algorithms. Most MAPS-SRTS subscales had acceptable inter-rater reliability, with an ICC of 0.97 for the revised audit tool.

Conclusions

The MAPS-SRTS audit tool is a reliable instrument for measuring the school travel environment for research and evaluation purposes, such as assessing human-scale determinants of active commuting to school behavior and documenting built environment changes from infrastructure interventions.
The Mentors in Violence Prevention programme: impact on students’ knowledge and attitudes related to violence, prejudice, and abuse, and willingness to intervene as a bystander in secondary schools in England
Authors: Butler Nadia , Quigg Zara , Wilson Charley , McCoy Ellie , Bates Rebecca
Published: March 2024

Background

Violence is a leading cause of death and disability for young people and has serious impacts on prospects across the lifecourse. The education sector is a crucial setting for preventing youth violence through incorporating programmes that address attitudes and behaviours. The Mentors in Violence Prevention (MVP) programme aims to change harmful attitudes and norms, and increase non-violent bystander intervention, through a peer mentoring approach. To date there is limited evidence on the effectiveness of the intervention in UK school settings. The aim of the current study was to evaluate the impact of the programme on students’ attitudes and knowledge related to violence prevention.

Methods

The study employed a mixed methods design. Pre and post surveys measured changes in students’ (aged 11–18) attitudes and knowledge related to violence prevention and bystander behaviour, gender stereotyping, acceptability of violence, and perceptions of others’ willingness to intervene. Interviews/focus groups with programme delivers and students, and anonymised programme data were used to explore and supplement survey findings.

Results

Overall, perceptions of the programme content and delivery were positive. Several beneficial impacts of the programme were found for mentors (students delivering the programme), including significant positive changes on measures of knowledge and attitudes towards violence prevention and the bystander approach, acceptability of violence perpetration, and perceptions of other students’ willingness to intervene (effect sizes were small-medium). However, the study found no significant change on any of the outcomes amongst mentees (younger students receiving the programme from mentors). Despite this, qualitative evidence suggested mentees enjoyed the content of the programme and the peer-led delivery, and this built relationships with older students. Qualitative evidence also identified additional benefits of the programme for mentors, including leadership and communication skills, and increased confidence and supportive relationships.

Conclusions

Evidence from this study suggests MVP is effective as a targeted programme for mentors, but no significant evidence was found to demonstrate its effectiveness as a universal bystander and violence prevention programme for mentees. Whilst further research with more robust study design is needed, developing mentors as leaders in violence prevention is a valuable impact of the programme in its own right.
Age at menarche and idiopathic pulmonary fibrosis: a two-sample mendelian randomization study
Authors: Cao Jiaqi , Ma Yazhou , Zhao Wei , Feng Chunlai
Published: March 2024

Background

Sex difference in the incidence rate of idiopathic pulmonary fibrosis (IPF) indicates that estrogen has a certain protective effect on the disease. Nevertheless, there is a dearth of study investigating the association between factors pertaining to endogenous estrogen exposure level, such as age at menarche (AAM) in women, and IPF. Our study intended to employ Mendelian randomization (MR) method to elucidate the causal association between AAM and IPF.

Methods

Our study utilized AAM as a measure of endogenous estrogen exposure and investigated its causal effect on the risk of IPF through MR. We employed the inverse variance weighted (IVW) method to assess the causal relationship between AAM and IPF risk, with supplementary analyses conducted using the weighted median estimator (WME) and MR-Egger method. Several sensitivity analyses were performed to assess the dependability of MR estimates.

Results

A total of 9 selected single nucleotide polymorphisms (SNPs) significantly associated with AAM were selected as instrumental variables. The IVW method showed that genetically later AAM was associated with an increased risk of IPF (odds ratio [OR] = 1.0014, 95%confidence interval [CI] = 1.0005–1.0023, p = 0.001). The median weighting method and the MR-Egger method obtained similar estimates, and no heterogeneity or pleiotropy was found, indicating that the results were robust.

Conclusions

Our MR study suggested a causal relationship between a later onset of menarche and a heightened susceptibility to IPF.
Systemized approach to equipping medical students with naloxone: a student-driven initiative to combat the opioid crisis
Authors: Saberi Shahin A. , Moore Sydney , Li Sienna , Mather Rory Vu , Daniels Mary B. , Shahani Amrita , Barreveld Antje , Griswold Todd , McGuire Patrick , Connery Hilary S.
Published: March 2024

Background

Naloxone is an effective and safe opioid reversal medication now approved by the U.S. Food and Drug Administration (FDA) for use with or without a prescription. Despite this, naloxone dissemination lags at a time when U.S. opioid-related mortality expands. The authors proposed distributing naloxone to all U.S. medical students using established statewide standing prescription orders for naloxone, eliminating the financial burden of over-the-counter costs on students and streamlining workflow for the pharmacy. By focusing naloxone distribution on medical students, we are able to capitalize on a group that is already primed on healthcare intervention, while also working to combat stigma in the emerging physician workforce.

Methods

Beginning August 2022, the authors established a partnership between Harvard Medical School (HMS) and the outpatient pharmacy at Brigham and Women’s Hospital (BWH) to facilitate access to naloxone for HMS medical students. BWH developed a HIPAA-secure electronic form to collect individual prescription information. BWH pharmacists processed submissions daily, integrating the naloxone prescription requests into their workflow for in-person pick-up or mail-order delivery. The electronic form was disseminated to medical students through a required longitudinal addiction medicine curriculum, listserv messaging, and an extracurricular harm reduction workshop.

Results

Over the 2022–2023 academic year, 63 medical students obtained naloxone kits (two doses per kit) through this collaboration.

Conclusions

We propose that medical schools advocate for a hospital pharmacy-initiated workflow focused on convenience and accessibility to expand naloxone access to medical students as a strategy to strengthen the U.S. emergency response and prevention efforts aimed at reducing opioid-related morbidity and mortality. Expansion of our program to BWH internal medicine residents increased our distribution to over 110 healthcare workers, and efforts to expand the program to other BWH training programs and clinical sites such as the emergency department and outpatient infectious disease clinics are underway. With more than 90,000 medical students in the U.S., we believe that widespread implementation of targeted naloxone training and distribution to this population is an accessible approach to combating the public health crisis of opioid-related overdoses.
Exploring the experiences of dentistry students of Tabriz University of Medical Sciences of academic motivation: a content analysis study
Authors: Katebi Katayoun , Ghaffarifar Saeideh , Dehghani Gholamali , Pourabbas Ahmad
Published: March 2024

Background

Students’ academic motivation is crucial to their academic performance, success, and future career performance. Understanding the experiences of students regarding academic motivation can help address this issue. This qualitative study aimed to explore the experiences of dentistry students of Tabriz University of Medical Sciences regarding academic motivation.

Methods

This qualitative content analysis study collected data through semi-structured individual interviews with open-ended questions. The collected data were then organized into codes, subcategories, categories, and themes. Extensive interviews, meetings, and active engagement with the participants were conducted to ensure the strength of the data collected.

Results

The results of this study yielded 20 subclasses and 11 classes. These codes, categories, and sub-categories were summarized into seven themes: self-efficacy, outcome expectations, outcome expectancies, emotional coping, self-regulation, situational perception, and environment.

Conclusion

This study showed that various concepts, from personal processes to environmental and social processes, play a role in students’ academic motivation. This study’s findings can contribute to developing more effective interventions to improve the motivation level of dentistry students.
AI in medical education: uses of AI in construction type A MCQs
Authors: Rezigalla Assad Ali
Published: March 2024

Background

The introduction of competency-based education models, student centers, and the increased use of formative assessments have led to demands for high-quality test items to be used in assessments. This study aimed to assess the use of an AI tool to generate MCQs type A and evaluate its quality.

Methods

The study design was cross-sectional analytics conducted from June 2023 to August 2023. This study utilized formative TBL. The AI tool (ChatPdf.com) was selected to generate MCQs type A. The generated items were evaluated using a questionnaire for subject experts and an item (psychometric) analysis. The questionnaire to the subject experts about items was formed based on item quality and rating of item difficulty.

Results

The total number of recurrent staff members as experts was 25, and the questionnaire response rate was 68%. The quality of the items ranged from good to excellent. None of the items had scenarios or vignettes and were direct. According to the expert’s rating, easy items represented 80%, and only two had moderate difficulty (20%). Only one item out of the two moderate difficulties had the same difficulty index. The total number of students participating in TBL was 48. The mean mark was 4.8 ± 1.7 out of 10. The KR20 is 0.68. Most items were of moderately difficult (90%) and only one was difficult (10%). The discrimination index of the items ranged from 0.77 to 0.15. Items with excellent discrimination represented 50% (5), items with good discrimination were 3 (30%), and only one time was poor (10%), and one was none discriminating. The non-functional distractors were 26 (86.7%), and the number of non-functional distractors was four (13.3%). According to distractor analysis, 60% of the items were excellent, and 40% were good. A significant correlation (p = 0.4, r = 0.30) was found between the difficulty and discrimination indices.

Conclusion

Items constructed using AI had good psychometric properties and quality, measuring higher-order domains. AI allows the construction of many items within a short time. We hope this paper brings the use of AI in item generation and the associated challenges into a multi-layered discussion that will eventually lead to improvements in item generation and assessment in general.
External inspection approaches and involvement of stakeholders’ views in inspection following serious incidents - a qualitative mixed methods study from the perspectives of regulatory inspectors
Authors: Øyri Sina Furnes , Wiig Siri , Anderson Janet E. , Bergerød Inger Johanne
Published: March 2024

Objective

The objective was to gain knowledge about how external inspections following serious incidents are played out in a Norwegian hospital context from the perspective of the inspectors, and whether stakeholders’ views are involved in the inspection.

Methods

Based on a qualitative mixed methods design, 10 government bureaucrats and inspectors situated at the National Board of Health Supervision and three County Governors in Norway, were strategically recruited, and individual semi-structured interviews were conducted. Key official government documents were selected, collected, and thematically analyzed along with the interview data.

Results

Our findings overall demonstrate two overarching themes: Theme (1) Perspectives on different external inspection approaches of responding and involving stakeholders in external inspection following serious incidents, Theme (2) Inspectors’ internal work practices versus external expectations. Documents and all participants reported a development towards new approaches in external inspection, with more policies and regulatory attention to sensible involvement of stakeholders. Involvement and interaction with patients and informal caregivers could potentially inform the case complexity and the inspector’s decision-making process. However, stakeholder involvement was sometimes complex and challenging due to e.g., difficult communication and interaction with patients and/or informal caregivers, due to resource demands and/or the inspector’s lack of experience and/or relevant competence, different perceptions of the principle of sound professional practice, quality, and safety. The inspectors considered balancing the formal objectives and expectations, with the expectations of the public and different stakeholders (i.e. hospitals, patients and/or informal caregivers) a challenging part of their job. This balance was seen as an important part of the continuous development of ensuring public trust and legitimacy in external inspection processes.

Conclusions and implications

Our study suggests that the regulatory system of external inspection and its available approaches of responding to a serious incident in the Norwegian setting is currently not designed to accommodate the complexity of needs from stakeholders at the levels of hospital organizations, patients, and informal caregivers altogether. Further studies should direct attention to how the wider system of accountability structures may support the internal work practices in the regulatory system, to better algin its formal objectives with expectations of the public.
Differentiated adaptative genetic architecture and language-related demographical history in South China inferred from 619 genomes from 56 populations
Authors: Sun Qiuxia , Wang Mengge , Lu Tao , Duan Shuhan , Liu Yan , Chen Jing , Wang Zhiyong , Sun Yuntao , Li Xiangping , Wang Shaomei , Lu Liuyi , Hu Liping , Yun Libing , Yang Junbao , Yan Jiangwei , Nie Shengjie , Zhu Yanfeng , Chen Gang , Wang Chuan-Chao , Liu Chao , He Guanglin , Tang Renkuan
Published: March 2024

Background

The underrepresentation of human genomic resources from Southern Chinese populations limited their health equality in the precision medicine era and complete understanding of their genetic formation, admixture, and adaptive features. Besides, linguistical and genetic evidence supported the controversial hypothesis of their origin processes. One hotspot case was from the Chinese Guangxi Pinghua Han people (GPH), whose language was significantly similar to Southern Chinese dialects but whose uniparental gene pool was phylogenetically associated with the indigenous Tai-Kadai (TK) people. Here, we analyzed genome-wide SNP data in 619 people from four language families and 56 geographically different populations, in which 261 people from 21 geographically distinct populations were first reported here.

Results

We identified significant population stratification among ethnolinguistically diverse Guangxi populations, suggesting their differentiated genetic origin and admixture processes. GPH shared more alleles related to Zhuang than Southern Han Chinese but received more northern ancestry relative to Zhuang. Admixture models and estimates of genetic distances showed that GPH had a close genetic relationship with geographically close TK compared to Northern Han Chinese, supporting their admixture origin hypothesis. Further admixture time and demographic history reconstruction supported GPH was formed via admixture between Northern Han Chinese and Southern TK people. We identified robust signatures associated with lipid metabolisms, such as fatty acid desaturases (FADS) and medically relevant loci associated with Mendelian disorder (GJB2) and complex diseases. We also explored the shared and unique selection signatures of ethnically different but linguistically related Guangxi lineages and found some shared signals related to immune and malaria resistance.

Conclusions

Our genetic analysis illuminated the language-related fine-scale genetic structure and provided robust genetic evidence to support the admixture hypothesis that can explain the pattern of observed genetic diversity and formation of GPH. This work presented one comprehensive analysis focused on the population history and demographical adaptative process, which provided genetic evidence for personal health management and disease risk prediction models from Guangxi people. Further large-scale whole-genome sequencing projects would provide the entire landscape of southern Chinese genomic diversity and their contributions to human health and disease traits.
Cannabis donation as a harm reduction strategy: a case study
Authors: Duhart Clarke Sarah E. , Victor Grant , Lynch Pamela , Suen Leslie W. , Ray Bradley
Published: March 2024

Background

The United States (US) continues to experience unprecedented rates of overdose mortality and there is increased need to identify effective harm reduction practices. Research from Canada describes cannabis donation through harm reduction agencies as an adjunctive strategy to mitigate the negative consequences of more harmful drugs. This case study describes the operational logistics, feasibility, and potential benefits of a cannabis donation program that was operated through a harm reduction program in rural Michigan.

Case presentation

We applied a community driven research approach to gather information from harm reduction program staff about the implementation and evolution of cannabis donation efforts in Michigan. We also examined 20-months (September 2021 through May 2023) of administrative data from a cannabis company to compare the sale and donation of cannabis products. Ten cannabis-experienced harm reduction clients received cannabis donations, with clinical staff determining client interest and appropriateness, and providing weekly pick-up or delivery. To expand product availability and sustainability, we examined administrative data from a commercialcannabis company that volunteered to provide donations. This administrative data suggests that while flower products constitute most of the adult and medical sales, edible, oil, and topical products predominated donations. Further, cost analysis suggests that donations represent only 1% of total gross sales and account for much less than the expected yearly donation amount.

Conclusions

Research suggests there is potential to reduce alcohol and drug use related harms of more dangerous substances through substitution with cannabis. This case study is the first to document cannabis donation as a harm reduction practice in the US and suggests potential for sustainability dependent on state laws. Findings from this case study provide a starting point for inquiry into cannabis donation as a harm reduction strategy in the US; future research is needed to fully understand the individual-level outcomes, public health impacts, necessary legal regulations, and best practices for cannabis donation programs through harm reduction organizations.
Interleukin-4 from curcumin-activated OECs emerges as a central modulator for increasing M2 polarization of microglia/macrophage in OEC anti-inflammatory activity for functional repair of spinal cord injury
Authors: Guo Jianbin , Tang Xiangwen , Deng Peng , Hui Hao , Chen Bo , An Jing , Zhang Gaorong , Shi Kuohao , Wang Jinchao , He Yuqing , Hao Dingjun , Yang Hao
Published: March 2024

Microglia/macrophages are major contributors to neuroinflammation in the central nervous system (CNS) injury and exhibit either pro- or anti-inflammatory phenotypes in response to specific microenvironmental signals. Our latest in vivo and in vitro studies demonstrated that curcumin-treated olfactory ensheathing cells (aOECs) can effectively enhance neural survival and axonal outgrowth, and transplantation of aOECs improves the neurological outcome after spinal cord injury (SCI). The therapeutic effect is largely attributed to aOEC anti-inflammatory activity through the modulation of microglial polarization from the M1 to M2 phenotype. However, very little is known about what viable molecules from aOECs are actively responsible for the switch of M1 to M2 microglial phenotypes and the underlying mechanisms of microglial polarization. Herein, we show that Interleukin-4 (IL-4) plays a leading role in triggering the M1 to M2 microglial phenotype, appreciably decreasing the levels of M1 markers IL‑1β, IL‑6, tumour necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) and elevating the levels of M2 markers Arg-1, TGF-β, IL-10, and CD206. Strikingly, blockade of IL-4 signaling by siRNA and a neutralizing antibody in aOEC medium reverses the transition of M1 to M2, and the activated microglia stimulated with the aOEC medium lacking IL-4 significantly decreases neuronal survival and neurite outgrowth. In addition, transplantation of aOECs improved the neurological function deficits after SCI in rats. More importantly, the crosstalk between JAK1/STAT1/3/6-targeted downstream signals and NF-κB/SOCS1/3 signaling predominantly orchestrates IL-4-modulated microglial polarization event. These results provide new insights into the molecular mechanisms of aOECs driving the M1-to-M2 shift of microglia and shed light on new therapies for SCI through the modulation of microglial polarization.
Multiregion WES of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns
Authors: Jiang Yu , Dong Yi-han , Zhao Shi-wei , Liu Dong-yu , Zhang Ji-yang , Xu Xiao-ya , Chen Hao , Chen Hao , Jin Jia-bin
Published: March 2024

Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease’s progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.
Modified gastro-soleus turn-down flap for chronic or neglected achilles tendon ruptures
Authors: Ibrahim Mohamed A. A. , Abdelkader Mohamed G. , Nematallah Samir A. , Elsawy Gamal A. , Alghandour Sameh A. , Shwitter Lotfy M.
Published: March 2024

Background

Achilles’ tendon chronic rupture is a common entity that is usually misdiagnosed or mistreated. Hence, she was presented to us later or with complications affecting her gait. Surgical resection is needed to either bridge the gap or reinforce the strength of the tendon repair.

Objectives

Our study's goal was to assess the clinical results of repairing chronic Achilles’ tendon lesions employing the middle segment of the proximal portion of the tendon (gastro-soleus), as a turn-down flap.

Methods

Our prospective interventional single arm study included 18 patients with chronic Achilles’ tendon rupture attending at Al-Azhar university hospitals in Cairo, Egypt from May 2020 to April 2023. Diagnosis of the patients was confirmed by radiographic and clinical investigations. They were all treated with the same open reconstruction procedure using a modified GSF. The average follow-up was 12 months. The results of this study were assessed by the Achilles tendon rupture score (ATRS), American Orthopedic Foot and Ankle Society (AOFAS) score, and capacity to perform repeated heel raises on the affected side.

Results

The mean operative time was 72.77 min. The median (IQR) time of reconstruction was 10 (8–12) after the injury. The median (IQR) length of flab was 4.5 (4.3–5) 9 (Table 2). No intraoperative complications occurred. The typical follow-up period was 12 months (6–18 months). In terms of the ATRS, we found a significant reduction from 82.8 ± 3 preoperatively to 20.8 ± 6.7 at 12 months postoperatively (P value = 0.001). As regards the AOFAS score, it was increased from 49.5 ± 10 preoperatively to 83.8 ± 8.5 12 months postoperatively (P = 0.001). In terms of the post operative complications, there was no re-rupture. Two patients experienced superficial wound infection which improved with daily dressing and antibiotics. Additionally, two patients had slight ankle stiffness four months after the operation, which improved after programmed rehabilitation at the sixth month.

Conclusion

The modified GSTF is a simple, safe, well-tolerated and effective method of treatment with excellent functional results and greater patient content.
Community-based surveillance programme evaluation using the platform Nyss implemented by the Somali Red Crescent Society—a mixed methods approach
Authors: Jung Julia , Larsen Tine Mejdell , Beledi Abdifatah Hussein , Takahashi Emi , Ahmed Abdirahman Omer , Reid Jenny , Kongelf Ida Anine
Published: March 2024

Background

Somali Red Crescent Society (SRCS), supported by Norwegian Red Cross, has implemented community-based surveillance (CBS) in Somaliland. This methodology aims to reduce the high risk of epidemics by strengthening early warning and response from and at community level, particularly where there is a weak public health surveillance system. CBS is implemented through SRCS community volunteers, who report signals from the community via SMS to the software platform Nyss. This paper presents key findings from the CBS programme evaluation.

Methods

A retrospective observational mixed-methods approach to evaluate the CBS programme was conducted, using routine CBS data from 2021 for Awdal and Togdheer regions and qualitative interviews with stakeholders’ representatives.

Results

The usefulness of the CBS programme in preventing, detecting, and responding to disease outbreaks was acknowledged by the stakeholders’ representatives. 83% of the signals in Awdal region matched a Community Case Definition (CCD) and were escalated to the Ministry of Health and Development (MoHD)). For Togdheer region, 97% were escalated. Verification of signals by supervisors and escalation to the authorities was done timely.Alert outcome and response action was not well recorded, therefore there is limited evidence on sensitivity. The programme was shown to be simple and can be flexibly adjusted for new diseases and changing CCDs.Stakeholders appreciated being engaged, the good collaboration, their participation throughout the implementation and expressed high acceptance of the programme.

Conclusion

CBS can support early warning and response for a variety of public health risks. Improved documentation for alert outcomes could help to better evaluate the sensitivity of CBS. A participatory approach is vital to achieve successful community volunteer engagement. Software tools, such as the Nyss platform, can be useful to support effective and efficient CBS implementation.
Preliminary efficacy of a transdiagnostic parent-led internet-delivered intervention for children with anxiety and depressive symptoms: a pilot randomized controlled trial
Authors: Poetar Costina-Ruxandra , Dobrean Anca , Andersson Gerhard
Published: March 2024

Background

There is extensive research indicating that transdiagnostic interventions are effective for adults and children with anxiety and depressive disorders; however, limited research has been conducted on the efficacy of such programs targeting parents of children with anxiety and depressive symptoms delivered via the Internet. This study aims to investigate the preliminary efficacy of a transdiagnostic Internet-delivered intervention for Romanian parents of children with elevated anxiety and depressive symptoms.

Methods

We conducted a single-blinded pilot randomized controlled trial. Forty-two parents of children with anxiety and depressive symptoms (Mage = 39.79, 78.6% women) from Romania were randomly assigned to one of the two groups, to ParentKIT, an Internet-delivered intervention based on Rational Emotive and Behavioral Therapy (n = 21), or to a delayed treatment condition (waitlist group) (n = 21). ParentKIT consisted of a brief transdiagnostic intervention delivered through nine modules with therapist guidance.

Results

A significant Group by Time effect was found for child emotional problems as reported by parents (Cohen’s d = − 0.85) and for parental self-efficacy (Cohen’s d = 0.71).

Conclusion

A transdiagnostic Internet-delivered intervention addressed to parents of children with elevated anxiety and depressive symptoms is a promising approach. Future research should include blind assessments as well as multiple outcome assessors and investigate the long-term efficacy of the intervention.

Trial registration

NCT05341297.
Voltammetric analysis of pholcodine on graphene-modified GNPs/PTs with green assessment
Authors: Abdelshafi Nahla A. , Darwish Hany W. , Alanazi Ashwag S. , Naguib Ibrahim A. , Elkhouly Hadeer H. , Khodary Nehal S. , Mohamed Ekram H.
Published: March 2024

Pholcodine, an anti-tussive medication widely used as an over-the-counter, OTC drug, has recently faced restrictions in several countries. This paper presents a sensitive electrochemical approach for pholcodine detection. The electrochemical method involved fabricating a graphene nanoplatelets electrode, incorporating polythiophene nanospheres polymer to promote electron transfer and increase the activated surface area. Characterization of the fabricated electrode was performed using transmission electron microscopy, ATR-Fourier-transform infrared spectroscopy, X-ray crystallography, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. The electrochemical behavior of pholcodine with the fabricated electrode was investigated using cyclic voltammetry, chronoamperometry, square wave voltammetry (SWV), and differential pulse voltammetry (DPV). The developed electrode led to a linear response for pholcodine ranging from 10 to 45 mg/L with detection limits of 1.41 and 1.51 mg/mL for SWV and DPV, respectively and quantification limits of 4.27 and 4.57 mg/L for SWV and DPV, respectively. The proposed method has accurately recovered pholcodine in spiked serum samples with a recovery percentage ranging from 1.2 to 2.9%. The optimized method is found to be accurate, precise, and robust by applying validation parameters provided by International Council for Harmonization. Two green metrics were computed to assess the method’s greenness, the findings showed that the developed method is environmentally friendly with minimum sample preparation steps.
Hepatozoon (Eucoccidiorida: Hepatozoidae) in wild mammals of the Americas: a systematic review
Authors: Thomas Richard , Santodomingo Adriana , Saboya-Acosta Liliana , Quintero-Galvis Julian F. , Moreno Lucila , Uribe Juan E. , Muñoz-Leal Sebastián
Published: March 2024

Abstract﻿

Background

The study of parasites provides insight into intricate ecological relationships in ecosystem dynamics, food web structures, and evolution on multiple scales. Hepatozoon (Eucoccidiorida: Hepatozoidae) is a genus of protozoan hemoparasites with heteroxenous life cycles that switch infections between vertebrates and blood-feeding invertebrates. The most comprehensive review of the genus was published 26 years ago, and currently there are no harmonized data on the epizootiology, diagnostics, genotyping methods, evolutionary relationships, and genetic diversity of Hepatozoon in the Americas.

Methods

Here, we provide a comprehensive review based on the PRISMA method regarding Hepatozoon in wild mammals within the American continent, in order to generate a framework for future research.

Results

11 out of the 35 countries of the Americas (31.4%) had data on Hepatozoon, with Carnivora and Rodentia orders having the most characterizations. Bats, ungulates, and shrews were the least affected groups. While Hepatozoon americanum, H. americanum-like, H. canis, H. didelphydis, H. felis, H. milleri, H. griseisciuri, and H. procyonis correspond to the identified species, a plethora of genospecies is pending for a formal description combining morphology and genetics. Most of the vectors of Hepatozoon in the Americas are unknown, but some flea, mite, and tick species have been confirmed. The detection of Hepatozoon has relied mostly on conventional polymerase chain reaction (PCR), and the implementation of specific real time PCR for the genus needs to be employed to improve its diagnosis in wild animals in the future. From a genetic perspective, the V4 region of the 18S rRNA gene has been widely sequenced for the identification of Hepatozoon in wild animals. However, mitochondrial and apicoplast markers should also be targeted to truly determine different species in the genus. A phylogenetic analysis of herein retrieved 18S ribosomal DNA (rDNA) sequences showed two main clades of Hepatozoon: Clade I associated with small mammals, birds, and herpetozoa, and Clade II associated with Carnivora. The topology of the tree is also reflected in the haplotype network.

Conclusions

Finally, our review emphasizes Hepatozoon as a potential disease agent in threatened wild mammals and the role of wild canids as spreaders of Hepatozoon infections in the Americas.

Graphical Abstract
Exploring the modulatory role of bovine lactoferrin on the microbiome and the immune response in healthy and Shiga toxin-producing E. coli challenged weaned piglets
Authors: Dierick Matthias , Ongena Ruben , Vanrompay Daisy , Devriendt Bert , Cox Eric
Published: March 2024

Background

Post-weaned piglets suffer from F18+Escherichia coli (E. coli) infections resulting in post-weaning diarrhoea or oedema disease. Frequently used management strategies, including colistin and zinc oxide, have contributed to the emergence and spread of antimicrobial resistance. Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated. Lactoferrin has shown promising results against porcine enterotoxigenic E. coli strains, both in vitro and in vivo.

Results

We investigated the influence of bovine lactoferrin (bLF) on the microbiome of healthy and infected weaned piglets. Additionally, we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E. coli (STEC) infection. Therefore, 2 in vivo trials were conducted: a microbiome trial and a challenge infection trial, using an F18+ STEC strain. BLF did not affect the α- and β-diversity. However, bLF groups showed a higher relative abundance (RA) for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa. When analysing the immune response upon infection, the STEC group exhibited a significant increase in F18-specific IgG serum levels, whereas this response was absent in the bLF group.

Conclusion

Taken together, the oral administration of bLF did not have a notable impact on the α- and β-diversity of the gut microbiome in weaned piglets. Nevertheless, it did increase the RA of the Actinobacteria phylum and Bifidobacterium genus, which have previously been shown to play an important role in maintaining gut homeostasis. Furthermore, bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.
MSCsDB: a database of single-cell transcriptomic profiles and in-depth comprehensive analyses of human mesenchymal stem cells
Authors: Yu Miao , Sui Ke , Wang Zheng , Zhang Xi
Published: March 2024

Mesenchymal stem cells (MSCs) possess multipotent properties that make them promising candidates for immunomodulation and regenerative medicine. However, MSC heterogeneity poses challenges to their research reproducibility and clinical application. The emergence of single-cell RNA sequencing (scRNA-seq) technology has enabled a thorough examination of MSC heterogeneity, underscoring the necessity for a specialized platform to systematically analyze the published datasets derived from MSC scRNA-seq experiments. However, large-scale integration and in-depth exploration of MSC scRNA-seq datasets to comprehensively depict their developmental patterns, relationships, and knowledge are still lacking. Here, we present MSCsDB (http://mscsdb.jflab.ac.cn:18088/index/), an interactive database that has been constructed using high-quality scRNA-seq datasets from all published sources on MSCs. MSCsDB provides a one-stop interactive query for regulon activities, gene ontology enrichment, signature gene visualization and transcription factor regulon analysis. Additionally, the dedicated module within MSCsDB was developed to facilitate the evaluation of MSC quality, thereby promoting the standardization of MSC subtype usage. Notably, MSCsDB enables users to analyze their MSCs scRNA-seq data directly, yielding visually appealing outputs of exceptional quality that can be conveniently downloaded via email. Furthermore, MSCsDB integrates the current comprehensive MSC atlas taxonomy, which includes 470,000 cells and 5 tissues from 26 subjects, as publicly available references. These references provide molecular characterization and phenotypic prediction for annotating MSC subsets. In summary, MSCsDB serves as a user-friendly and contemporary data repository for human MSCs, offering a dedicated platform that enables users to effectively conduct comprehensive analyses on their individual MSCs scRNA-seq data.