bluuebunny/crossref_metadata_2025 huggingface dataset:
ILIAD: a suite of automated Snakemake workflows for processing genomic data for downstream applications
Authors: Herrick Noah , Walsh Susan
Published: November 2023

Background

Processing raw genomic data for downstream applications such as imputation, association studies, and modeling requires numerous third-party bioinformatics software tools. It is highly time-consuming and resource-intensive with computational demands and storage limitations that pose significant challenges that increase cost. The use of software tools independent of one another, in a disjointed stepwise fashion, increases the difficulty and sets forth higher error rates because of fragmented job executions in alignment, variant calling, and/or build conversion complications. As sequencing data availability grows, the ability for biologists to process it using stable, automated, and reproducible workflows is paramount as it significantly reduces the time to generate clean and reliable data.

Results

The Iliad suite of genomic data workflows was developed to provide users with seamless file transitions from raw genomic data to a quality-controlled variant call format (VCF) file for downstream applications. Iliad benefits from the efficiency of the Snakemake best practices framework coupled with Singularity and Docker containers for repeatability, portability, and ease of installation. This feat is accomplished from the onset with download acquisitions of any raw data type (FASTQ, CRAM, IDAT) straight through to the generation of a clean merged data file that can combine any user-preferred datasets using robust programs such as BWA, Samtools, and BCFtools. Users can customize and direct their workflow with one straightforward configuration file. Iliad is compatible with Linux, MacOS, and Windows platforms and scalable from a local machine to a high-performance computing cluster.

Conclusion

Iliad offers automated workflows with optimized time and resource management that are comparable to other workflows available but generates analysis-ready VCF files from the most common datatypes using a single command. The storage footprint challenge of genomic data is overcome by utilizing temporary intermediate files before the final VCF is generated. This file is ready for use in imputation, genome-wide association study (GWAS) pipelines, high-throughput population genetics studies, select gene candidate studies, and more. Iliad was developed to be portable, compatible, scalable, robust, and repeatable with a simplistic setup, so biologists that are less familiar with programming can manage their own big data with this open-source suite of workflows.
Increased infiltration of CD4+ T cell in the complement deficient lymphedema model
Authors: Nishioka Toshihiko , Katayama Kei-ichi , Kumegawa Shinji , Isono Kyoichi , Baba Takashi , Tsujimoto Hiroshi , Yamada Gen , Inoue Norimitsu , Asamura Shinichi
Published: November 2023

Background

Lymphedema is an intractable disease that can be caused by injury to lymphatic vessels, such as by surgical treatments for cancer. It can lead to impaired joint mobility in the extremities and reduced quality of life. Chronic inflammation due to infiltration of various immune cells in an area of lymphedema is thought to lead to local fibrosis, but the molecular pathogenesis of lymphedema remains unclear. Development of effective therapies requires elucidation of the immunological mechanisms involved in the progression of lymphedema. The complement system is part of the innate immune system which has a central role in the elimination of invading microbes and acts as a scavenger of altered host cells, such as apoptotic and necrotic cells and cellular debris. Complement-targeted therapies have recently been clinically applied to various diseases caused by complement overactivation. In this context, we aimed to determine whether complement activation is involved in the development of lymphedema.

Results

Our mouse tail lymphedema models showed increased expression of C3, and that the classical or lectin pathway was locally activated. Complement activation was suggested to be involved in the progression of lymphedema. In comparison of the C3 knockout (KO) mouse lymphedema model and wild-type mice, there was no difference in the degree of edema at three weeks postoperatively, but the C3 KO mice had a significant increase of TUNEL+ necrotic cells and CD4+ T cells. Infiltration of macrophages and granulocytes was not significantly elevated in C3 KO or C5 KO mice compared with in wild-type mice. Impaired opsonization and decreased migration of macrophages and granulocytes due to C3 deficiency should therefore induce the accumulation of dead cells and may lead to increased infiltration of CD4+ T cells.

Conclusions

Vigilance for exacerbation of lymphedema is necessary when surgical treatments have the potential to injure lymphatic vessels in patients undergoing complement-targeted therapies or with complement deficiency. Future studies should aim to elucidate the molecular mechanism of CD4+ T cell infiltration by accumulated dead cells.
Stimulus-responsive proteins involved in multi-process regulation of storage substance accumulation during rice grain filling under elevated temperature
Authors: Zhao Yufei , Yin Tongyang , Ran Xuan , Liu Wenzhe , Shen Yingying , Guo Hao , Peng Yuxuan , Zhang Chen , Ding Yanfeng , Tang She
Published: November 2023

Background

The intensified global warming during grain filling deteriorated rice quality, in particular increasing the frequency of chalky grains which markedly impact market value. The formation of rice quality is a complex process influenced by multiple genes, proteins and physiological metabolic processes. Proteins responsive to stimulus can adjust the ability of plants to respond to unfavorable environments, which may be an important protein involved in the regulation of quality formation under elevated temperature. However, relatively few studies have hindered our further understanding of rice quality formation under elevated temperature.

Results

We conducted the actual field elevated temperature experiment and performed proteomic analysis of rice grains at the early stage of grain filling. Starting with the response to stimulus in GO annotation, 22 key proteins responsive to stimulus were identified in the regulation of grain filling and response to elevated temperature. Among the proteins responsive to stimulus, during grain filling, an increased abundance of signal transduction and other stress response proteins, a decreased abundance of reactive oxygen species-related proteins, and an increased accumulation of storage substance metabolism proteins consistently contributed to grain filling. However, the abundance of probable indole-3-acetic acid-amido synthetase GH3.4, probable indole-3-acetic acid-amido synthetase GH3.8 and CBL-interacting protein kinase 9 belonged to signal transduction were inhibited under elevated temperature. In the reactive oxygen species-related protein, elevated temperature increased the accumulation of cationic peroxidase SPC4 and persulfide dioxygenase ETHE1 homolog to maintain normal physiological homeostasis. The increased abundance of alpha-amylase isozyme 3E and seed allergy protein RA5 was related to the storage substance metabolism, which regulated starch and protein accumulation under elevated temperature.

Conclusion

Auxin synthesis and calcium signal associated with signal transduction, other stress responses, protein transport and modification, and reactive oxygen species-related proteins may be key proteins responsive to stimulus in response to elevated temperature. Alpha-amylase isozyme 3E and seed allergy protein RA5 may be the key proteins to regulate grain storage substance accumulation and further influence quality under elevated temperature. This study enriched the regulatory factors involved in the response to elevated temperature and provided a new idea for a better understanding of grain response to temperature.
The significance of nonurgent psychiatric emergencies in an ED: a retrospective study
Authors: Kirchner Heribert , Ullrich Heiko , Neu Peter , Hulsmans Nik , Juckel Georg , Brzoska Patrick
Published: November 2023

Background

In emergency departments, patients with mental health conditions are a major concern and make up the third or fourth of the most common diagnosis seen during all consultations. Over the past two decades, there has been a noticeable rise in the number of cases, particularly due to an increase in nonurgent visits for somatic medical issues. The significance of nonurgent visits for psychiatric patients is yet to be determined. This study aims to uncover the significance and identify the characteristics of this group.

Methods

A retrospective analysis of psychiatric emergency visits at an interdisciplinary emergency department of a German general hospital in 2015 was conducted. For this purpose, patient records were reviewed and evaluated. An analysis was conducted based on the German definition of psychiatric emergencies according to the German guidelines for emergency psychiatry.

Results

A total of 21,124 emergency patients visited the evaluated Emergency Department. Of this number, 1,735 psychiatric patient records were evaluated, representing 8.21% of the total population. Nearly 30% of these patients did not meet any emergency criteria according to German guidelines. Significant differences were observed between previously treated patients and those presenting for the first time.

Conclusions

The high proportion of nonurgent psychiatric patients in the total volume of psychiatric emergency contacts indicates a possible control and information deficit within the emergency system. Just as prior research has emphasized the importance of investigating nonurgent somatic medical visits, it is equally imperative to delve into studies centered around psychiatric nonurgent presentations.
Application of contrast-enhanced ultrasound in renal space-occupying lesion puncture biopsy
Authors: Jia Zhi-Ying , Yang Feng , Zhang Wei , Li Wei-Wei
Published: November 2023

Objective

The purpose of this study was to investigate the utility of contrast-enhanced ultrasound (CEUS) in percutaneous renal space-occupying lesion puncture biopsy.

Methods

Ultrasound (US)-guided percutaneous needle biopsies were performed on 55 patients with renal space-occupying lesions, and the results were analyzed retrospectively. The US group included 36 patients receiving conventional US, and the contrast-enhanced ultrasound (CEUS) group included 22 patients, including 19 patients receiving CEUS directly and 3 patients receiving additional enhanced ultrasound due to the first conventional ultrasound puncture failure. The relevant data were subjected to statistical analysis.

Results

The results of this study showed that the successful rate of obtaining effective tissue (100% vs. 75%) and the puncture accuracy (100% vs. 88.89%) in CEUS group were significantly higher than those in US group (P < 0.05). CEUS-guided puncture biopsy of renal mass, especially in the case of urothelial carcinoma of the renal pelvis, outperforms conventional ultrasound, and the difference was statistically significant (P < 0.05).

Conclusion

Percutaneous renal space-occupying lesion puncture biopsies aided by CEUS yield more effective tissue and improved puncture accuracy.
Global, regional and national burden of male infertility in 204 countries and territories between 1990 and 2019: an analysis of global burden of disease study
Authors: Huang Baoyi , Wang Zhaojun , Kong Yanxiang , Jin Mengqi , Ma Lin
Published: November 2023

Background

Many countries and regions have experienced male fertility problems due to various influencing factors, especially in less developed countries. Unlike female infertility, male infertility receives insufficient attention. Understanding the changing patterns of male infertility in the world, different regions and different countries is crucial for assessing the global male fertility and reproductive health.

Methods

We obtained data on prevalence, years of life lived with disability (YLD), age-standardized rates of prevalence (ASPR) and age-standardized YLD rate (ASYR) from the Global Burden of Disease Study 2019. We analyzed the burden of male infertility at all levels, including global, regional, national, age stratification and Socio-demographic Index (SDI).

Results

In 2019, the global prevalence of male infertility was estimated to be 56,530.4 thousand (95% UI: 31,861.5–90,211.7), reflecting a substantial 76.9% increase since 1990. Furthermore, the global ASPR stood at 1,402.98 (95% UI: 792.24–2,242.45) per 100,000 population in 2019, representing a 19% increase compared to 1990. The regions with the highest ASPR and ASYR for male infertility in 2019 were Western Sub-Saharan Africa, Eastern Europe, and East Asia. Notably, the prevalence and YLD related to male infertility peaked in the 30–34 year age group worldwide. Additionally, the burden of male infertility in the High-middle SDI and Middle SDI regions exceeded the global average in terms of both ASPR and ASYR.

Conclusion

The global burden of male infertility has exhibited a steady increase from 1990 to 2019, as evidenced by the rising trends in ASPR and ASYR, particularly in the High-middle and Middle SDI regions. Notably, the burden of male infertility in these regions far exceeds the global average. Additionally, since 2010, there has been a notable upward trend in the burden of male infertility in Low and Middle-low SDI regions. Given these findings, it is imperative to prioritize efforts aimed at improving male fertility and reproductive health.
Trends in age-specific varicella incidences following the introduction of the general recommendation for varicella immunization in Germany, 2006–2022
Authors: Moek Felix , Siedler Anette
Published: November 2023

Background

In Germany, general childhood varicella vaccination has been recommended since 2004. A feared effect of low vaccination coverage is a possible shift in incidence from children to teenagers and young adults who are at higher risk of severe outcomes. If true, this shift would possibly necessitate changes to the national immunization strategy.

We aimed to evaluate the effects of the general vaccination recommendation on age-specific varicella incidences in Germany in general and examine specifically whether a shift from children to teenagers (15 to 19 years) has occurred.

Methods

Trends in age-specific incidences were evaluated using triangulation with the following datasets: national mandatory notification data (N) (2014–2022), billing data of the statutory health insurance associations (I) (2009–2017) and data from a doctor's sentinel system (S) (2006–2017). Similar clinical case definitions were used in N and S, while I used ICD-10-codes. Age groups were stratified as available in all three systems. Incidences per year were calculated based on the total population (N), the number of statutory health insured (I), and extrapolated from S to the total population.

Results

During all years of observation, age-specific incidences have dropped significantly across all age-groups for S und I. The age groups (under 10 years) with initially highest incidences were the ones with the strongest reductions (under 1 year: -90%, 1–4 years: -95.5%, 5–9 years: -89.2% for S; -67.7%, -78%, -79.3% for I). A single 53.1% increase in the low incidence in S among 15–19-year olds observed in 2017 compared to 2016 could not be confirmed in N or I. Increases in incidences during the first two years of N are probably due to improved notification behaviour over these years. In 2019, all age-specific incidences increased (N), with 15 to 19-year olds showing the highest relative increase (28.2%).

Conclusions

Since the introduction of the general vaccine recommendation against varicella, incidences across all age-groups have declined significantly. Available data indicate no evidence for a shift in disease incidence to older age groups. Every incidence increase beyond childhood age should however be followed up closely. So far, children and adolescents have both benefitted from the current vaccination strategy.
Treatment-seeking behaviour among 15–49-year-olds with self-reported heart disease, cancer, chronic respiratory disease, and diabetes: a national cross-sectional study in India
Authors: Netterström-Wedin Fredh , Dalal Koustuv
Published: November 2023

Background

Eighty per cent of India´s non-communicable disease (NCD) mortality is due to four conditions: heart disease, cancer, chronic respiratory disease, and diabetes, which are primarily cause-amenable through treatment. Based on Andersen’s behavioural model of health services use, the current study aimed to identify the predisposing, enabling, and need factors associated with treatment-seeking status among people self-reporting the four main NCDs in India.

Methods

Cross-sectional study using secondary data. Usual residents aged 15–49 who self-reported cancer (n = 1 056), chronic respiratory disease (n = 10 534), diabetes (n = 13 501), and/or heart disease (n = 5 861) during the fifth National Family and Health Survey (NFHS-5), 2019–21, were included. Treatment-seeking status was modelled separately for each disease using survey-adjusted multivariable logistic regression.

Results

3.9% of India´s 15–49-year-old population self-reported ≥ 1 of the four main NCDs (0.1% cancer, 1.4% chronic respiratory disease, 2% diabetes, 0.8% heart disease). The percentage that had sought treatment for their condition(s) was 82%, 68%, 76%, and 74%, respectively. Greater age and having ≥ 1 of the NCDs were associated with greater odds of seeking disease-specific treatment. People in the middle or lower wealth quintiles had lower odds of seeking care than the wealthiest 20% for all conditions. Women with diabetes or chronic respiratory disease had greater odds of seeking disease-specific treatment than men. Muslims, the unmarried, and those with health insurance had greater odds of seeking cancer treatment than Hindus, the married, and the uninsured.

Conclusion

Predisposing, enabling, and need factors are associated with treatment-seeking status among people reporting the four major NCDs in India, suggesting that multiple processes inform the decision to seek disease-specific care among aware cases. Successfully encouraging and enabling as many people as possible who knowingly live with major NCDs to seek treatment is likely contingent on a multi-pronged approach to healthcare policy-making. The need to improve treatment uptake through accessible healthcare is further underscored by the fact that one-fifth (cancer) to one-third (chronic respiratory disease) of 15–49-year-olds reporting a major NCD have never sought treatment despite being aware of their condition.
Intrusive rumination and academic burnout among adolescents in ethnic minority areas of China during the COVID-19 pandemic: PTSS as mediator and cognitive reappraisal as moderator
Authors: He Linhui , Yuan Xiaojiao , Chen Qiuyan , Wang Xiaogang
Published: November 2023

Background

The COVID-19 pandemic has had a significant negative impact on public health, prompting scholarly research in related fields. In this context, the present study reveals the psychological characteristics of adolescents in ethnic minority areas of China approximately five months after the 2020 outbreak of the COVID-19 pandemic, explores the relationship between intrusive rumination and academic burnout, and examines the role of post-traumatic stress symptoms (PTSS) and cognitive reappraisal in the relationship to provide an empirical foundation for developing effective psychological interventions for adolescents in the wake of the pandemic.

Methods

Based on cluster sampling, 941 middle school students (65.36% female, 74.71% senior high, Mage=15.95) in ethnic minority areas of China were surveyed using the Event Related Rumination Scale, Adolescent Academic Burnout Scale, Post-traumatic Stress Checklist Scale, Emotion Regulation Strategy Scale, and a self-designed demographic questionnaire.

Results

During the COVID-19 pandemic, 7.44% of Chinese ethnic minority adolescents in our study sample were classified as PTSD positive, and 10.95% exhibited partial PTSD. Intrusive rumination significantly predicted academic burnout, and PTSS played a key mediating role between the two, accounting for 58.51% of the total effect. After controlling for PTSS, cognitive reappraisal moderated the effects of intrusive rumination on academic burnout. Specifically, the effect of intrusive rumination on academic burnout decreased with improvement in cognitive reappraisal.

Conclusions

Intrusive rumination indirectly affected academic burnout in adolescents through PTSS as a crucial mediator, and the remnant direct effect was alleviated by cognitive reappraisal. This finding emphasises the importance of adopting a comprehensive approach that encompasses cognitive, emotional, and physiological symptoms to understand and address academic burnout among adolescents during the COVID-19 pandemic.
Application of a modified osteotomy and positioning integrative template system (MOPITS) based on a truncatable reconstruction model in the precise mandibular reconstruction with fibula free flap: a pilot clinical study
Authors: Sun Qing , Zhu Zhihui , Meng Fanhao , Zhao Ruiqi , Li Xing , Long Xiao , Li Yansheng , Dong Haitao , Zhang Tao
Published: November 2023

Background

Mandibular defects can greatly affect patients' appearance and functionality. The preferred method to address this issue is reconstructive surgery using a fibular flap. The current personalized guide plate can improve the accuracy of osteotomy and reconstruction, but there are still some problems such as complex design process and time-consuming. Therefore, we modified the conventional template to serve the dual purpose of guiding the mandible and fibula osteotomy and facilitating the placement of the pre-bent titanium.

Methods

The surgery was simulated preoperatively using Computer-Aided Design (CAD) technology. The template and truncatable reconstruction model were produced in the laboratory using 3D printing. After pre-bending the titanium plate according to the contour, the reconstruction model was truncated and the screw trajectory was transferred to form a modified osteotomy and positioning integrative template system (MOPITS). Next, the patient underwent a composite template-guided vascularized fibula flap reconstruction of the mandible. All cases were reviewed for the total operative time and accuracy of surgery.

Results

The procedures involved 2–4 fibular segments in 15 patients, averaging 3 fibular segments per procedure. The osteotomy error is 1.01 ± 1.02 mm, while the reconstruction angular error is 1.85 ± 1.69°. The preoperative and postoperative data were compared, and both p > 0.05. During the same operation, implant placement was performed on four patients, with an average operative time of 487.25 ± 60.84 min. The remaining malignant tumor patients had an average operative time of 397.18 ± 73.09 min. The average postoperative hospital stay was 12.95 ± 3.29 days.

Conclusions

This study demonstrates the effectiveness of MOPITS in facilitating precise preoperative planning and intraoperative execution of fibula flap reconstruction. MOPITS represents a promising and reliable tool for reconstructive surgery, particularly for inexperienced surgeons navigating the challenges of mandible defect reconstruction.
Diagnostic significance of neutrophil to lymphocyte ratio in endometriosis: a systematic review and meta-analysis
Authors: Tabatabaei Fatemeh , Tahernia Hossein , Ghaedi Arshin , Bazrgar Aida , Khanzadeh Shokoufeh
Published: November 2023

Background

The purpose of this systematic review and meta-analysis was to compile existing evidence on the significance of the NLR in predicting endometriosis in order to aid clinical decision-making and outcomes.

Methods

We searched ProQuest, Web of Science, and PubMed for related studies published before January 2, 2023. Standardized mean difference (SMD) with a 95% confidence interval (CI) was reported for each outcome. Because a significant level of heterogeneity was found, we used the random-effects model to calculate pooled effects. We used Newcastle-Ottawa Scale (NOS) for quality assessment.

Results

Overall, 18 article with were included in the analysis. A random-effect model revealed that patients with endometriosis had elevated levels of NLR compared to healthy controls (SMD = 0.79, 95% CI = 0.33 to 1.25,P < 0.001). Patients with endometriosis had elevated levels of NLR compared to those with other benign tumors (SMD = 0.85, 95% CI = 0.17 to 1.53,P = 0.014). In addition, NLR level of patients with stage III and IV endometriosis was not different from that of patients with stage I and II endometrioma (SMD = 0.30, 95% CI = -0.14 to 0.74,P = 0.18). However, NLR level was not different between endometriosis patients with and without peritoneal lesions (SMD = -0.12, 95% CI = -0.34to 0.10,P = 0.28), between patients with and without endometrioma (SMD = 0.20, 95% CI = -0.15 to 0.55,P = 0.26) and between endometriosis patients with and without deep lesions (SMD = 0.04, 95% CI = -0.20 to 0.28,P = 0.72). The pooled sensitivity of NLR was 0.67 (95% CI = 0.60–0.73), and the pooled specificity was 0.68 (95% CI, 0.62–0.73).

Conclusions

NLR might be utilized in clinics as a possible predictor to help clinicians diagnose endometriosis in affected women.
Effect of mentorship and a mHealth application in updating provider skills and knowledge in maternal and newborn care in two informal settlements of Nairobi
Authors: Ndwiga Charity , Abuya Timothy , Okondo Chantalle , Akinyi Sharon , Wickramanayake Anneka , Warren Charlotte E.
Published: November 2023

Background

Children and women in urban informal settlements have fewer choices to access quality maternal and newborn health care. Many facilities serving these communities are under-resourced and staffed by fewer providers with limited access to skills updates. We sought to increase provider capacity by equipping them with skills to provide general and emergency obstetric and newborn care in 24 facilities serving two informal settlements in Nairobi. We present evidence of the combined effect of mentorship using facility-based mentors who demonstrate skills, support skills drills training, and provide practical feedback to mentees and a self-guided online learning platform with easily accessible EmONC information on providers’ smart phones.

Methods

We used mixed methods research with before and after cross-sectional provider surveys conducted at baseline and end line. During end line, 18 in-depth interviews were conducted with mentors and mentees who were exposed, and providers not exposed to the intervention to explore effectiveness and experience of the intervention on quality maternal health services.

Results

Results illustrated marked improvement from ability to identify antepartum hemorrhage (APH), postpartum hemorrhage (PPH), manage retained placenta, ability to identify and manage obstructed labour, Pre-Eclampsia and Eclampsia (PE/E), puerperal sepsis, and actions taken to manage conditions when they present. Overall, out of 95 elements examined there were statistically significant improvements of both individual scores and overall scores from 29/95 at baseline (30.5%) to 44.3/95 (46.6%) during end line representing a 16- percentage point increase (p > 0.001). These improvements were evident in public health facilities representing a 17.3% point increase (from 30.9% at baseline to 48.2% at end line, p > 0.001). Similarly, providers working in private facilities exhibited a 15.8% point increase in knowledge from 29.7% at baseline to 45.5% at end line (p = 0.0001).

Conclusion

This study adds to the literature on building capacity of providers delivering Maternal and Newborn Health (MNH) services to women in informal settlements. The complex challenges of delivering MNH services in informal urban settings where communities have limited access require a comprehensive approach including ensuring access to supplies and basic equipment. Nevertheless, the combined effects of the self-guided online platform and mentorship reinforces EmONC knowledge and skills. This combined approach is more likely to improve provider competency, and skills as well as improving maternal and newborn health outcomes.
Enhancing collaborative learning in health management education: an investigation of Padlet-mediated interventions and the influence of flexible thinking
Authors: Naamati-Schneider Lior , Alt Dorit
Published: November 2023

This study had three primary goals. First, it aimed to craft an intervention program centered around collaborative learning enabled by Padlet. Second, it aimed to gauge the perceptions of health management students regarding this intervention and how it affected their collaborative learning experiences. Additionally, the third objective of the study aimed to investigate how students’ flexible thinking within the learning process might shape their perceptions of the advantages derived from this instructional activity within the domain of online collaborative learning. Data for the analysis were gathered from 100 Israeli undergraduate students by two measurements: Flexible thinking in learning and Student perceptions of collaborative learning via Padlet. The intervention program included several stages. First, the students discussed the pedagogic objective of using Padlet. In the second stage, the students were presented with ill-structured problems related to the course content. Each group had to choose one problem and analyze it from three perspectives discussed in the course—healthcare provider, patient, and organization. Next, the students presented and explained their solutions employing the shared knowledge base. The final work was presented in different formats using various technologies. The PLS-SEM analysis has corroborated our hypothesis that students’ flexible thinking might positively contribute to their perception of Padlet utilization. According to the empirical model, in general, students who perceived themselves as more flexible were found more receptive to utilizing the proposed technological tool (Padlet) and hence tended to appreciate its function as a collaborative learning platform enabler. This study mainly underscores the important role flexible thinking plays in motivating managers and medical professionals to embrace innovative technologies or methods for teamwork, that could enable them to weigh arguments, seek alternative solutions to authentic problems, and adjust their approaches effectively and collaboratively as new challenges emerge.
Developing a digital informed consent app: opportunities and challenges of a new format to inform and obtain consent in public health research
Authors: Haring Luuk V. , Hall Joy T. , Janssen Anton , Johannes J. Marleen , Verhoeff Arnoud P. , Ujcic-Voortman Joanne K.
Published: November 2023

Background

Informed consent procedures for large population-based cohort studies should be comprehensive and easy-to-use. This is particularly challenging when participants from different socio-economic groups and multicultural ethnic backgrounds are involved. Recently, more and more studies have tried to use multimedia in informed consent procedures. We describe the development and testing of a digital informed consent app and elaborate on whether this may contribute to a comprehensive and practical procedure to obtain informed consent for public health research.

Methods

In a sample of parents with young children, we used a mixed method approach to study the user experience of an informed consent app and evaluate whether it can be used to adequately inform people and register their consent. Through semi-structured interviews we investigated participants’ experiences with and opinions about the app, with a special focus on comprehensibility of the content and the usability of the app. Information retention questions were asked to evaluate to what extent participants could recall key aspects of the provided study information.

Results

The 30 participants in this study used the app between 4 and 15 min to give their consent. Overall, they found the app well-designed, informative and easy to use. To learn more about the study for which informed consent is asked, most of the participants chose to watch the animated film, which was generally found to convey information in a clear manner. The identification process was met with mixed reactions, with some feeling it as a secure way to give consent, while for others it contradicted their view of using data anonymously. Information retention questions showed that while all participants remembered various aspects of the study, fewer than half answered all four questions satisfactorily.

Conclusion

Our study shows that a well-designed informed consent app can be an effective tool to inform eligible participants and to record consents. Still, some issues remain, including trust barriers towards the identification procedure and lack of information retention in some participants. When implementing consent procedures that incorporate digital formats, it may be beneficial to also invest in a complementary face-to-face recruitment approach.
Can we achieve better trial recruitment by presenting patient information through multimedia? Meta-analysis of ‘studies within a trial’ (SWATs)
Authors: Madurasinghe Vichithranie W. , Knapp Peter , Eldridge Sandra , Collier David , Treweek Shaun , Rick Jo , Graffy Jonathan , Parker Adwoa , Salisbury Chris , Torgerson David , Jolly Kate , Sidhu Manbinder S. , Fife-Schaw Christopher , Hull Mark A. , Sprange Kirsty , Brettell Elizabeth , Bhandari Sunil , Montgomery Alan , Bower Peter
Published: November 2023

Background

People need high-quality information to make decisions about research participation. Providing information in written format alone is conventional but may not be the most effective and acceptable approach. We developed a structure for the presentation of information using multimedia which included generic and trial-specific content. Our aim was to embed ‘Studies Within A Trial’ (SWATs) across multiple ongoing trials to test whether multimedia presentation of patient information led to better rates of recruitment.

Methods

Five trials included a SWAT and randomised their participants to receive a multimedia presentation alongside standard information, or standard written information alone. We collected data on trial recruitment, acceptance and retention and analysed the pooled results using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised following an invitation to take part.

Results

Five SWATs provided data on the primary outcome of proportion of participants randomised. Multimedia alongside written information results in little or no difference in recruitment rates (pooled odds ratio = 0.96, 95% CI: 0.79 to 1.17, p-value = 0.671, I2 = 0%). There was no effect on any other outcomes.

Conclusions

Multimedia alongside written information did not improve trial recruitment rates.

Trial registration

ISRCTN71952900, ISRCTN 06710391, ISRCTN 17160087, ISRCTN05926847, ISRCTN62869767.
Triglycerides/HDL cholesterol ratio and type 2 diabetes incidence: Panasonic Cohort Study 10
Authors: Yuge Hiroki , Okada Hiroshi , Hamaguchi Masahide , Kurogi Kazushiro , Murata Hiroaki , Ito Masato , Fukui Michiaki
Published: November 2023

Background

Previous studies have investigated the association between the ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) and the incidence of diabetes in adults and discovered that a high TG/HDL-C ratio was linked to an elevated risk of new-onset diabetes. However, the comparison of predicting diabetes development among lipid profiles including the TG/HDL-C ratio, and the ratio of TG/HDL-C cut-off value has received limited attention. We examined the relationship between diabetes onset and the TG/HDL-C ratio in addition to the applicable cut-off value for predicting diabetes onset.

Methods

This study included 120,613 participants from the health examination database at Panasonic Corporation from 2008 to 2017. Cox regression analysis employing multivariable models was used to investigate the association between lipid profiles, particularly the ratio of TG/HDL-C and the development of type 2 diabetes (T2D). The multivariable model was adjusted for age, sex, BMI, systolic blood pressure, plasma glucose levels after fasting, smoking status, and exercise habits. Areas under time-dependent receiver operating characteristic (ROC) curves (AUCs) were employed to assess the prediction performance and cut-off values of each indicator. A fasting plasma glucose level of 126 mg/dL, a self-reported history of diabetes, or usage of antidiabetic medicines were used to identify T2D.

Results

During the course of the study, 6,080 people developed T2D. The median follow-up duration was 6.0 (3–10) years. Multivariable analysis revealed that the ratio of TG/HDL-C (per unit, HR; 1.03 [95% CI 1.02–1.03]) was substantially linked to the risk of incident T2D. AUC and cut-off points for the ratio of TG/HDL-C for T2D development after 10 years were 0.679 and 2.1, respectively. Furthermore, the AUC of the ratio of TG/HDL-C was considerably larger compared to that of LDL-C, HDL-C, and TG alone (all P < 0.001). We discovered an interaction effect between sex, BMI, and lipid profiles in subgroup analysis. Females and participants having a BMI of < 25 kg/m2 showed a higher correlation between lipid profile levels and T2D onset.

Conclusions

The ratio of TG/HDL-C was found to be a stronger predictor of T2D development within 10 years than LDL-C, HDL-C, or TG, indicating that it may be useful in future medical treatment support.
Molecular surveillance of chloroquine resistance in Plasmodium vivax isolates from malaria cases in Yunnan Province of China using pvcrt-o gene polymorphisms
Authors: Ding Hongyun , Dong Ying , Deng Yan , Xu Yanchun , Liu Yan , Wu Jing , Chen Mengni , Zhang Canglin , Liu Li , Lin Yingkun
Published: November 2023

Background

The efficacy of chloroquine treatment for vivax malaria has been rarely evaluated due to a lack of an appropriate testing method. The objective of this study was to conduct molecular monitoring of chloroquine resistance in Plasmodium vivax strains from vivax malaria patients in Yunnan Province, focusing on the analysis of polymorphism in the P. vivax chloroquine resistance transporter protein orthologous gene (pvcrt-o).

Methods

In accordance with the principles of a cohort study, blood samples were collected from malaria cases diagnosed with a P. vivax mono-infection in Yunnan Province from 2020 to 2022. Segmental PCR was used to amplify the whole pvcrt-o gene in the blood samples and their products were subsequently sequenced. The sequencing data were arranged to obtain the full coding DNA sequence (CDS) as well as the gene’s promoter region sequences. The CDSs were aligned with the reference sequence (XM_001613407.1) of the P. vivax SalI isolate to identify the mutant loci.

Results

From a total of 375 blood samples taken from vivax malaria cases, 272 both whole gene CDSs (1272–1275 bp) and promoter DNA sequences (707 bp) of pvcrt-o gene were obtained. Among the whole CDSs, there were 7 single nucleotide polymorphic sites in which c.7 A>G was the minor allele frequency (MAF) site with 4.4% (12/272) detection rate. The mutation detection rate showed a significant decrease from 9.8% (10/102) in 2020 to 1.1% (1/92) in 2021 and 1.3% (1/78) in 2022, indicating statistical significance (χ2 = 11.256, P < 0.05). Among the identified 12 haplotypes, the majority of which were wild type (75.7%; 206/272). These four mutant haplotypes (Hap_3, Hap_5, Hap_9, and Hap_10) were classified as “K10 insertion type” and accounted for 12.1% (33/272). The detection rate of Hap_3 increased from 1.0% (1/102) in 2020 to 13.0% (12/92) in 2021 and 14.1% (11/78) in 2022, indicating statistical significance. A total of 23.8% (65/272) of the samples exhibited 14 bp (bp) deletions in the promoter region, occurring most frequently in the wild type haplotype (Hap_1) samples at a rate of 28.6% (59/206).

Conclusions

In recent years in Yunnan Province, a notable proportion of vivax malaria patients are infected by P. vivax strains with a “K10 insertion” and partial sequence deletions in the promoter region of the pvcrt-o gene, necessitating vigilance.
The role of germanium in diseases: exploring its important biological effects
Authors: Luo Xiao , Sun Jiaxue , Kong Deshenyue , Lei Yi , Gong Fangyou , Zhang Tong , Shen Zongwen , Wang Kunhua , Luo Huayou , Xu Yu
Published: November 2023

With the development of organic germanium and nanotechnology, germanium serves multiple biological functions, and its potential value in biochemistry and medicine has increasingly captured the attention of researchers. In recent years, germanium has gradually gained significance as a material in the field of biomedicine and shows promising application prospects. However, there has been a limited amount of research conducted on the biological effects and mechanisms of germanium, and a systematic evaluation is still lacking. Therefore, the aim of this review is to systematically examine the application of germanium in the field of biomedicine and contribute new insights for future research on the functions and mechanisms of germanium in disease treatment. By conducting a comprehensive search on MEDLINE, EMBASE, and Web of Science databases, we systematically reviewed the relevant literature on the relationship between germanium and biomedicine. In this review, we will describe the biological activities of germanium in inflammation, immunity, and antioxidation. Furthermore, we will discuss its role in the treatment of neuroscience and oncology-related conditions. This comprehensive exploration of germanium provides a valuable foundation for the future application of this element in disease intervention, diagnosis, and prevention.
Enhancing nasopharyngeal carcinoma cell radiosensitivity by suppressing AKT/mTOR via CENP-N knockdown
Authors: Wu Li-Zhi , Zou You , Wang Bin-Ru , Ni Hai-Feng , Kong Yong-Gang , Hua Qing-Quan , Chen Shi-Ming
Published: November 2023

Objective

Investigating the impact of centromere protein N (CENP-N) on radiosensitivity of nasopharyngeal carcinoma (NPC) cells.

Methods

Using immunohistochemistry and immunofluorescence to detect CENP-N expression in tissues from 35 patients with radiosensitive or radioresistant NPC. Assessing the effect of combined CENP-N knockdown and radiotherapy on various cellular processes by CCK-8, colony formation, flow cytometry, and Western blotting. Establishing a NPC xenograft model. When the tumor volume reached 100 mm3, a irradiation dose of 6 Gy was given, and the effects of the combined treatment were evaluated in vivo using immunofluorescence and Western blotting techniques.

Results

The level of CENP-N was significantly reduced in radiosensitive tissues of NPC (p < 0.05). Knockdown of CENP-N enhanced NPC radiosensitivity, resulting in sensitizing enhancement ratios (SER) of 1.44 (5-8 F) and 1.16 (CNE-2Z). The combined treatment showed significantly higher levels of proliferation suppression, apoptosis, and G2/M phase arrest (p < 0.01) compared to either CENP-N knockdown alone or radiotherapy alone. The combined treatment group showed the highest increase in Bax and γH2AX protein levels, whereas the protein Cyclin D1 exhibited the greatest decrease (p < 0.01). However, the above changes were reversed after treatment with AKT activator SC79. In vivo, the mean volume and weight of tumors in the radiotherapy group were 182 ± 54 mm3 and 0.16 ± 0.03 g. The mean tumor volume and weight in the combined treatment group were 84 ± 42 mm3 and 0.04 ± 0.01 g.

Conclusion

Knockdown of CENP-N can enhance NPC radiosensitivity by inhibiting AKT/mTOR.
β-adrenergic signaling triggers enteric glial reactivity and acute enteric gliosis during surgery
Authors: Leven Patrick , Schneider Reiner , Schneider Linda , Mallesh Shilpashree , Vanden Berghe Pieter , Sasse Philipp , Kalff Jörg C. , Wehner Sven
Published: November 2023

Background

Enteric glia contribute to the pathophysiology of various intestinal immune-driven diseases, such as postoperative ileus (POI), a motility disorder and common complication after abdominal surgery. Enteric gliosis of the intestinal muscularis externa (ME) has been identified as part of POI development. However, the glia-restricted responses and activation mechanisms are poorly understood. The sympathetic nervous system becomes rapidly activated by abdominal surgery. It modulates intestinal immunity, innervates all intestinal layers, and directly interfaces with enteric glia. We hypothesized that sympathetic innervation controls enteric glia reactivity in response to surgical trauma.

Methods

Sox10iCreERT2/Rpl22HA/+ mice were subjected to a mouse model of laparotomy or intestinal manipulation to induce POI. Histological, protein, and transcriptomic analyses were performed to analyze glia-specific responses. Interactions between the sympathetic nervous system and enteric glia were studied in mice chemically depleted of TH+ sympathetic neurons and glial-restricted Sox10iCreERT2/JellyOPfl/+/Rpl22HA/+ mice, allowing optogenetic stimulation of β-adrenergic downstream signaling and glial-specific transcriptome analyses. A laparotomy model was used to study the effect of sympathetic signaling on enteric glia in the absence of intestinal manipulation. Mechanistic studies included adrenergic receptor expression profiling in vivo and in vitro and adrenergic agonism treatments of primary enteric glial cell cultures to elucidate the role of sympathetic signaling in acute enteric gliosis and POI.

Results

With ~ 4000 differentially expressed genes, the most substantial enteric glia response occurs early after intestinal manipulation. During POI, enteric glia switch into a reactive state and continuously shape their microenvironment by releasing inflammatory and migratory factors. Sympathetic denervation reduced the inflammatory response of enteric glia in the early postoperative phase. Optogenetic and pharmacological stimulation of β-adrenergic downstream signaling triggered enteric glial reactivity. Finally, distinct adrenergic agonists revealed β-1/2 adrenoceptors as the molecular targets of sympathetic–driven enteric glial reactivity.

Conclusions

Enteric glia act as early responders during post-traumatic intestinal injury and inflammation. Intact sympathetic innervation and active β-adrenergic receptor signaling in enteric glia is a trigger of the immediate glial postoperative inflammatory response. With immune-activating cues originating from the sympathetic nervous system as early as the initial surgical incision, adrenergic signaling in enteric glia presents a promising target for preventing POI development.
Conceptualizing a less paranoid schizophrenia
Authors: Long James , Hull Rachel
Published: November 2023

Schizophrenia stands as one of the most studied and storied disorders in the history of clinical psychology; however, it remains a nexus of conflicting and competing conceptualizations. Patients endure great stigma, poor treatment outcomes, and condemnatory prognosis. Current conceptualizations suffer from unstable categorical borders, heterogeneity in presentation, outcome and etiology, and holes in etiological models. Taken in aggregate, research and clinical experience indicate that the class of psychopathologies oriented toward schizophrenia are best understood as spectra of phenomenological, cognitive, and behavioral modalities. These apparently taxonomic expressions are rooted in normal human personality traits as described in both psychodynamic and Five Factor personality models, and more accurately represent explicable distress reactions to biopsychosocial stress and trauma. Current categorical approaches are internally hampered by axiomatic bias and systemic inertia rooted in the foundational history of psychological inquiry; however, when such axioms are schematically decentralized, convergent cross-disciplinary evidence outlines a more robust explanatory construct. By reconceptualizing these disorders under a dimensional and cybernetic model, the aforementioned issues of instability and inaccuracy may be resolved, while simultaneously opening avenues for both early detection and intervention, as well as for more targeted and effective treatment approaches.