bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge and willingness to donate kidney for transplantation among general population in Saudi Arabia
Authors: Alshehri Mohammed , Tawhari Ibrahim , Alqahtani Thekra S. , Alqahtani Alhanouf Y. , Al Jallal Marwah S. , Asiri Ghufran B. , Alshahrani Maymunah A. , Majrashi Maryam A. , Khuzayyim Ahmed A. , Albishri Fai D. , Alshahrani Wajan A.
Published: August 2024

Introduction

Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD), offering a superior quality of life and extended survival compared to other renal replacement therapies. As the number of ESRD patients grows, so does the demand for organ transplants. The prevalence of ESRD is anticipated to escalate further due to the rising rates of diabetes mellitus (DM), hypertension (HTN), and obesity. Organ donation, particularly from living donors, remains the main source of transplants in the region, despite the notable underutilization of potential deceased donors’ organs. The objective of this research is to assess the level of knowledge, attitudes, and willingness to donate kidneys among the general population, a pivotal step in addressing the organ shortage crisis.

Methods

This cross-sectional study was conducted in the Aseer region of Saudi Arabia using a previously validated questionnaire. The questionnaire collected demographic data and insights into general attitudes, knowledge, and beliefs about organ donation. Logistic regression was used to identify predictors of knowledge and willingness to donate.

Results

The study involved 705 participants, predominantly young adults with a high level of education. Awareness of kidney donation was high, and knowledge about donation was broad, especially regarding religious permissibility and awareness of the donor registry. However, only 25% expressed willingness to donate their kidneys, and a 4% were already registered as donors. Furthermore, higher educational level was not associated with higher odds of knowledge or willingness to donate.

Conclusion

Despite the considerable awareness, actual donor registration rates were low, highlighting the necessity for targeted educational interventions and a deeper understanding of the cultural and socioeconomic barriers that exist.
Co-producing an intervention to prevent mental health problems in children and young people in contact with child welfare services
Authors: McGovern Ruth , Balogun-Katung Abisola , Artis Benjamin , Alderson Hayley , Brown Eric , Diggle Tim , Lingam Raghu , McArdle Paul , Rankin Judith , Thomason Paige , Kaner Eileen
Published: August 2024

Background

Children and young people (CYP) in contact with child welfare services are at high risk of developing mental health problems. There is a paucity of evidenced-based preventative interventions provided to this population.

Objective

This project worked in partnership with CYP, their parents/caregivers and the professionals who support them to co-produce a preventative mental health intervention for CYP in contact with child welfare services.

Participants and setting

We recruited a purposive sample of CYP in contact with child welfare services (n = 23), parents/caregivers (n = 18) and practitioners working within child welfare services and mental health services (n = 25) from the North East of England and convened co-production workshops (n = 4).

Methods

This project followed the established principles for intervention development, applying the six steps to quality intervention development (6SQUID) approach. The mixed method research consisted of four work packages with continuous engagement of stakeholders throughout the project. These were: a systematic review of reviews; focus groups with practitioners; interviews with parents/caregivers and CYP; co-production workshops.

Results

We identified that the primary risk factor affecting CYP in contact with child welfare services is the experience of childhood adversity. The quality of relationships that the CYP experiences with both their parent/caregivers and the professionals involved in their care are considered to be the main factors amenable to change.

Conclusions

We found that a trauma-informed, activity-based intervention with an embedded family-focused component provided to CYP who have experienced adversity is most likely to prevent mental health problems in those in contact with child welfare services.
Comparison of univariate and bivariate Poisson regression methods in the analysis of determinants of female schooling and fertility in Malawi
Authors: Mponda Eneles , Kaombe Tsirizani Mwalimu
Published: August 2024

Recent research has established existence of a correlation between women’s education and fertility, suggesting that they share similar risk factors. However, in many studies, the two variables were analysed separately, which could bias the conclusions by undermining the apparent correlations of such paired outcomes. In this article, the univariate and bivariate Poisson regression models were applied to nationally representative sample of 24,562 women from the 2015-16 Malawi demographic and health survey to examine the risk factors of women’s education levels and fertility. The R software version 4.1.2 was used for the analyses. The results showed that estimates from the bivariate Poisson model were consistent with those obtained from the separate univariate Poisson models. The sizes of estimates of coefficients, their standard errors, p-values, and directions were comparable in both bivariate and univariate Poisson models. Using either the univariate or bivariate Poisson model, it was found that the age of a woman at first sexual experience, her current age, household wealth index, and contraceptive usage were significantly associated with both the woman’s schooling and fertility. The study further revealed that ethnicity, religion, and region of residence impacted education level only and not fertility. Similarly, marital status and occupation impacted fertility only and not education. The study also found that higher education levels were linked to a lower number of children, with a strong negative correlation of -0.62 between the two variables. The study recommends using bivariate Poisson regression for analysing paired count response data, when there is an apparent covariance between the outcome variables. The results suggest that efforts by policymakers to achieve the desired women’s sexual and reproductive health in sub-Saharan Africa should be intertwined with improving women’s and girls’ education attainment in the region.
The influence of care home registration type and size on senior care leader’s confidence to provide palliative and end-of-life care: an explanatory sequential mixed methods study
Authors: Tunnard India , Sleeman Katherine E. , Bradshaw Andy , Bone Anna E. , Evans Catherine J.
Published: August 2024

Background

Care home staff are key providers of palliative and end-of-life care. Yet, little is known about how care home characteristics can influence care leader’s confidence in their ability to provide optimal palliative and end-of-life care.

Aim

To understand the influence of care home registration type (nursing, residential or dual registered) and size on senior care leader’s confidence to provide palliative and end-of-life care.

Design

An explanatory sequential mixed methods study comprising an online cross-sectional survey (including the Palliative Care Self-Efficacy Scale) and qualitative individual interviews. Analysis of survey data used a multivariate logistic regression and qualitative interview data used Framework Analysis. A ‘Following the Thread’ method was undertaken for data integration.

Setting/participants

UK care home senior care leaders, purposively sampled by registration type, size and geographical location.

Results

The online survey (N = 107) results indicated that nursing home senior care leaders had higher confidence scores on the Palliative Care Self-Efficacy Scale than residential care home leaders (aOR: 3.85, 95% CI 1.20-12.31, p = 0.02). Care home size did not show effect when adjusting for registration type (medium - aOR 1.71, 95% CI 0.59–4.97, p = 0.33; large – aOR 0.65, 95% CI 0.18–2.30, p = 0.5). Interviews (n = 27) identified three themes that promote confidence, (1) ‘feelings of preparedness’ stemming from staff expertise and experience and care home infrastructure, (2) ‘partnership working’ with external services as a valued member of the multidisciplinary team, and (3) a shared language developed from end-of-life care guidance.

Conclusion

Care home senior care leader’s confidence is influenced by care home characteristics, particularly availability of on-site registered nurses and the infrastructure of large care homes. All care home leaders benefit from training, working with external, multidisciplinary teams and use of guidance. However, mechanisms to achieve this differed by care home type and size. Further exploration is needed on successful integration of palliative care services and interventions to enhance confidence in residential care homes.
An online training and feedback module enhances the musculoskeletal examination performance of medical interns
Authors: Arteaga Matías , Vidal Catalina , Ruz Cristián , Zilleruelo Raúl , Pino Ernesto , Dauvergne Javier , Besa Pablo , Irarrázaval Sebastián
Published: August 2024

Background

Pathologies of the locomotor system are frequent and can cause disability and impact the quality of life of the people affected. In recent years, online training and feedback have emerged as learning tools in many fields of medicine.

Objective

This study aims to evaluate medical interns’ musculoskeletal examination performance after completing an online training and feedback module.

Methods

This study employed a quasi-experimental design. Medical interns were invited to complete a 4-week musculoskeletal physical examination training and feedback module via an e-learning platform. The course included written and audiovisual content pertaining to medical history, physical examination, and specific tests for the diagnosis of the most common knee, spine, shoulder, ankle, and foot conditions. Before and after completing the module, their ability to perform the physical examination was evaluated using an objective structured clinical examination (OSCE) with simulated patients that took place face-to-face. A control group of experts was assessed using the OSCE, and their performance was compared to that of the interns before and after the training. At the end of the module feedback on the OSCE was provided to participants through the platform asynchronously and two evaluation questions about the user experience were conducted at the end of the study.

Results

A total of 35 subjects were assessed using the OSCE, including 29 interns and 6 experts. At the beginning of the training module, the group of interns obtained an average score of 50.6 ± 15.1. At the end of the module, 18 interns retook the OSCE, and their performance increased significantly to an average of 76.6 ± 12.8 (p < 0.01). Prior to the training, the experts performed significantly better than the interns (71.2 vs. 50.6; p = 0.01). After the interns received the training and feedback, there were no significant differences between the two groups (71.2 vs. 76.6; p = 0.43). Two evaluation questions were conducted at the end of the study, revealing that 93% of the participants affirm that the training module will be useful in their clinical practice, and 100% of the participants would recommend the training module to a colleague.

Conclusion

The online training and feedback module enhances the musculoskeletal examination performance of medical interns.
Implementing care-related services in care units - an interview study
Authors: Reichert Dorothea , Gummesson Karl , Wallin Lars , Dahlström Tobias
Published: August 2024

Background

The growing concern about a dwindling healthcare workforce, exacerbated by demographic changes, calls for innovative solutions. One viable approach involves implementing new professional roles and restructuring existing healthcare teams within hospital care units.

Objectives

To evaluate the implementation of an innovative task-shifting concept, care-related services (CRS), from the managers’ perspective in somatic care units across the hospitals in a region in Sweden.

Methods

The qualitative study was conducted in 2022, after the implementation of CRS. Individual interviews were conducted with 24 key stakeholders, including 14 care unit managers, six CRS managers, and four process managers. A qualitative content analysis was performed, utilizing the Consolidated Framework of Implementation Research (CFIR).

Results

The implementation of CRS involved collaboration between care unit managers, CRS managers, and project managers, alongside CRS staff, registered nurses (RNs), and licensed vocational nurses (LVNs). In particular, their roles encompassed defining boundaries, establishing routines, and managing personnel. Throughout the implementation process, challenges emerged, stemming from undefined goals, difficulties in recruiting qualified CRS staff, and issues associated with seamlessly integrating CRS into existing work routines. These challenges arose due to a constrained timeframe, widespread team apprehension, shortcomings in the training of CRS staff, unclear task allocation, and an increased workload for care unit managers. Factors associated with successful CRS implementation included effective cooperation among managers and an open-minded approach.

Conclusions

Our findings highlight the crucial role of clear communication, effective recruitment, integration of CRS staff, clarification of roles, responsibilities, and defined goals for successful CRS implementation.
Machine learning enabled classification of lung cancer cell lines co-cultured with fibroblasts with lightweight convolutional neural network for initial diagnosis
Authors: Germain Adam , Sabol Alex , Chavali Anjani , Fitzwilliams Giles , Cooper Alexa , Khuon Sandra , Green Bailey , Kong Calvin , Minna John , Kim Young-Tae
Published: August 2024

Background

Identification of lung cancer subtypes is critical for successful treatment in patients, especially those in advanced stages. Many advanced and personal treatments require knowledge of specific mutations, as well as up- and down-regulations of genes, for effective targeting of the cancer cells. While many studies focus on individual cell structures and delve deeper into gene sequencing, the present study proposes a machine learning method for lung cancer classification based on low-magnification cancer outgrowth patterns in a 2D co-culture environment.

Methods

Using a magnetic well plate holder, circular pattern lung cancer cell clusters were generated among fibroblasts, and daily images were captured to monitor cancer outgrowth over a 9-day period. These outgrowth images were then augmented and used to train a convolutional neural network (CNN) model based on the lightweight TinyVGG architecture. The model was trained with pairs of classes representing three subtypes of NSCLC: A549 (adenocarcinoma), H520 (squamous cell carcinoma), and H460 (large cell carcinoma). The objective was to assess whether this lightweight machine learning model could accurately classify the three lung cancer cell lines at different stages of cancer outgrowth. Additionally, cancer outgrowth images of two patient-derived lung cancer cells, one with the KRAS oncogene and the other with the EGFR oncogene, were captured and classified using the CNN model. This demonstration aimed to investigate the translational potential of machine learning-enabled lung cancer classification.

Results

The lightweight CNN model achieved over 93% classification accuracy at 1 day of outgrowth among A549, H460, and H520, and reached 100% classification accuracy at 7 days of outgrowth. Additionally, the model achieved 100% classification accuracy at 4 days for patient-derived lung cancer cells. Although these cells are classified as Adenocarcinoma, their outgrowth patterns vary depending on their oncogene expressions (KRAS or EGFR).

Conclusions

These results demonstrate that the lightweight CNN architecture, operating locally on a laptop without network or cloud connectivity, can effectively create a machine learning-enabled model capable of accurately classifying lung cancer cell subtypes, including those derived from patients, based upon their outgrowth patterns in the presence of surrounding fibroblasts. This advancement underscores the potential of machine learning to enhance early lung cancer subtyping, offering promising avenues for improving treatment outcomes in advanced stage-patients.
Fluctuations in serum lipid levels during neoadjuvant treatment as novel predictive and prognostic biomarkers for locally advanced breast cancer: a retrospective analysis based on a prospective cohort
Authors: Chen Xinru , Zhao Yingying , Wang Yaohui , Ye Yumei , Xu Shuguang , Zhou Liheng , Lin Yanping , Lu Jingsong , Yin Wenjin
Published: August 2024

Background

With increasing attention given to host-specific lipid metabolism status, it is of urgent need to identify lipid metabolism indices with predictive or prognostic value in locally advanced breast cancer patients treated with neoadjuvant chemotherapy (NAC), and to evaluate the performance improvement by incorporating them into the existing Neo-Bioscore staging system.

Methods

Patients from a prospectively maintained database of locally advanced breast cancer patients who received radical surgery after NAC between January 2014 to December 2020 were enrolled in this study. The enrolled patients were randomly divided into a training set and a test set at a ratio of 6:4. The random forest algorithm was applied to rank the importance of prognostic factors, top-ranked lipid metabolism indices of which were then incorporated into Neo-Bioscore to construct an updated prognostic model. The performances of these two models were compared in both training set and test set from multiple perspectives. Study outcomes included disease-free survival (DFS), relapse-free survival (RFS), distance-recurrence-free survival (DRFS), locoregional-recurrence-free survival (LRFS) and overall survival (OS).

Results

A total of 200 eligible patients were included in this study. After a median follow-up of 4.73 years, it was demonstrated that the relative increase in total cholesterol (TC; DFS: HR = 4.782, 95%CI 1.410 ~ 16.217,P = 0.012) and low-density lipoprotein (LDL; DFS: HR = 4.622, 95%CI 1.517 ~ 14.088,P = 0.007) during NAC led to poorer survival outcomes. Patients with either a higher body mass index (BMI) or elevated LDL during NAC had a worse prognosis (DFS: HR = 6.351, 95%CI 1.938 ~ 20.809,P = 0.002; OS, HR = 6.919, 95%CI 1.296 ~ 36.932,P = 0.024). Incorporating BMI and LDL fluctuations during NAC into Neo-Bioscore improved the prognostic stratification, especially in terms of LRFS (P = 0.046 vs.P = 0.65) and OS (P = 0.013 vs.P = 0.61). Multidimensional evaluation confirmed the improvement in model fit and clinical use for the updated model in both training set and test set.

Conclusions

This is the first study to illustrate the relative elevation of LDL and TC levels during NAC as independent prognosticators for locally advanced breast cancer. This is also the first attempt to incorporate lipid metabolism indices into the original Neo-Bioscore staging system, which further improves the prognostic stratification of patients receiving NAC.
Patterns of health workforce turnover and retention in Aboriginal Community Controlled Health Services in remote communities of the Northern Territory and Western Australia, 2017–2019
Authors: Veginadu Prabhakar , Russell Deborah J. , Zhao Yuejen , Guthridge Steven , Ramjan Mark , Jones Michael P. , Mathew Supriya , Fitts Michelle S. , Murakami-Gold Lorna , Campbell Narelle , Tangey Annie , Boffa John , Rossingh Bronwyn , Schultz Rosalie , Humphreys John , Wakerman John
Published: August 2024

Background

Aboriginal Community Controlled Health Services (ACCHSs) in Australia aim to optimise access to comprehensive and culturally safe primary health care (PHC) for Aboriginal populations. Central to quality service provision is the retention of staff. However, there is lack of published research reporting patterns of staff turnover and retention specific to ACCHSs. This study quantified staff turnover and retention in regional and remote ACCHSs in the Northern Territory (NT) and Western Australia (WA), and examined correlations between turnover and retention metrics, and ACCHSs’ geographical and demographic characteristics.

Methods

The study used 2017–2019 payroll data for health workers in 22 regional and remote PHC clinics managed by 11 ACCHSs. Primary outcome measures included annual turnover and 12-month stability rates, calculated at both clinic and organisation levels.

Results

There was a median of five client-facing (Aboriginal health practitioners, allied health professionals, doctors, nurses/midwives, and ‘other health workers’ combined) and two non-client-facing (administrative and physical) staff per remote clinic, at any timepoint. Mean annual turnover rates for staff were very high, with 151% turnover rates at the clinic level and 81% turnover rates at the organisation level. Mean annual turnover rates for client-facing staff were 164% and 75%, compared to 120% and 98% for non-client-facing staff, at clinic and organisational levels, respectively. Mean 12-month stability rates were low, with clinic-level stability rates of only 49% and organisation-level stability rates of 58%. Mean annual clinic-level turnover rates were 162% for non-Aboriginal staff and 81% for Aboriginal staff. Both workforce metrics were moderately to highly correlated with the relative remoteness of clinics, size of regular clients serviced, and average annual headcount of employees in each clinic (p values < 0.01).

Conclusions

Participating ACCHSs in remote NT and WA have very high turnover and low retention of healthcare staff. Overall, clinic-level turnover rates increase as distance from regional centres increases and are lower for Aboriginal staff, suggesting that greater employment of Aboriginal staff could help stabilise staffing. Improved retention could reduce burden on ACCHSs’ resources and may also support quality of service delivery due to improved cultural safety and continuity of care.
Facilitating co-research: lessons learned from reflection forms within three participatory action research projects
Authors: Emke Helga , Vandendriessche Ann , Chinapaw Mai , Deforche Benedicte , Verloigne Maïté , Altenburg Teatske , Anselma Manou
Published: August 2024

Background

Mutual learning and shared decision-making are key elements of Participatory Action Research (PAR), highlighting the important role of the facilitator to support this. This study aims to illustrate how a facilitator can contribute to successful PAR sessions based on the reflection of three PAR projects.

Methods

Participatory sessions took place with adolescents for 3–4 school years. After each session (n = 252 sessions across three projects), facilitators filled in a reflection form that assessed the group process and their facilitating role. Facilitators independently coded a selection of 135 reflection forms partly deductive and partly inductive based on core PAR principles derived from a pragmatic literature search.

Results

A well-prepared session – for example, including active and creative participatory methods and a clearly stated goal – contributed to efficiency and the necessary flexibility. Making agreements, making sure everyone is heard and taking 'fun-time' appeared important for creating and maintaining a safe, functional and positive atmosphere. Finally, facilitators needed to encourage co-researchers to take the lead and adapt to the group dynamics, to ensure ownership and shared decision-making.

Conclusion

In-depth qualitative analyses of a standardized reflection form used in three different PAR projects resulted in various lessons to support facilitators in collaborating with co-researchers in PAR projects.
Sil1-deficient fibroblasts generate an aberrant extracellular matrix leading to tendon disorganisation in Marinesco-Sjögren syndrome
Authors: Amodei Laura , Ruggieri Anna Giulia , Potenza Francesca , Viele Marianna , Dufrusine Beatrice , Franciotti Raffaella , Pietrangelo Laura , Ardini Matteo , Stuppia Liborio , Federici Luca , De Laurenzi Vincenzo , Sallese Michele
Published: August 2024

Background

Marinesco-Sjögren syndrome (MSS) is an autosomal recessive neuromuscular disorder that arises in early childhood and is characterized by congenital cataracts, myopathy associated with muscle weakness, and degeneration of Purkinje neurons leading to ataxia. About 60% of MSS patients have loss-of-function mutations in the SIL1 gene. Sil1 is an endoplasmic reticulum (ER) protein required for the release of ADP from the master chaperone Bip, which in turn will release the folded proteins. The expression of non-functional Sil1 leads to the accumulation of unfolded proteins in the ER and this triggers the unfolded protein response (UPR). A dysfunctional UPR could be a key element in the pathogenesis of MSS, although our knowledge of the molecular pathology of MSS is still incomplete.

Methods

RNA-Seq transcriptomics was analysed using the String database and the Ingenuity Pathway Analysis platform. Fluorescence confocal microscopy was used to study the remodelling of the extracellular matrix (ECM). Transmission electron microscopy (TEM) was used to reveal the morphology of the ECM in vitro and in mouse tendon.

Results

Our transcriptomic analysis, performed on patient-derived fibroblasts, revealed 664 differentially expressed (DE) transcripts. Enrichment analysis of DE genes confirmed that the patient fibroblasts have a membrane trafficking issue. Furthermore, this analysis indicated that the extracellular space/ECM and the cell adhesion machinery, which together account for around 300 transcripts, could be affected in MSS. Functional assays showed that patient fibroblasts have a reduced capacity of ECM remodelling, reduced motility, and slower spreading during adhesion to Petri dishes. TEM micrographs of negative-stained ECM samples from these fibroblasts show differences of filaments in terms of morphology and size. Finally, structural analysis of the myotendinous junction of the soleus muscle and surrounding regions of the Achilles tendon revealed a disorganization of collagen fibres in the mouse model of MSS (woozy).

Conclusions

ECM alterations can affect the proper functioning of several organs, including those damaged in MSS such as the central nervous system, skeletal muscle, bone and lens. On this basis, we propose that aberrant ECM is a key pathological feature of MSS and may help explain most of its clinical manifestations.
Robotic assessment of bilateral and unilateral upper limb functions in adults with cerebral palsy
Authors: Poitras I. , Dukelow S. P. , Campeau-Lecours A. , Mercier C.
Published: August 2024

Background

Children with unilateral cerebral palsy (CP) exhibit motor impairments predominantly on one side of the body, while also having ipsilesional and bilateral impairments. These impairments are known to persist through adulthood, but their extent have not been described in adults with CP. This study’s aim is to characterize bilateral and unilateral upper limbs impairments in adults with CP.

Methods

Nineteen adults with CP (34.3 years old ± 11.5) performed three robotic assessments in the Kinarm Exoskeleton Lab, including two bilateral tasks (Object Hit [asymmetric independent goals task] and Ball on Bar [symmetric common goal task]) and one unilateral task (Visually Guided Reaching, performed with the more affected arm [MA] and less affected arm [LA]). Individual results were compared to sex, age and handedness matched normative data, describing the proportion of participants exhibiting impairments in each task-specific variable (e.g., Hand speed), each performance category (e.g., Feedforward control) and in global task performance. Associations were assessed using Spearman correlation coefficients between: 1: the results of the MA and LA of each limb in the unilateral task; and 2: the results of each limb in the unilateral vs. the bilateral tasks.

Results

The majority of participants exhibited impairments in bilateral tasks (84%). The bilateral performance categories (i.e., Bimanual) identifying bilateral coordination impairments were impaired in the majority of participants (Object Hit: 57.8%; Ball on Bar: 31.6%). Most of the participants were impaired when performing a unilateral task with their MA arm (63%) and a smaller proportion with their LA arm (31%). The Feedforward control was the unilateral performance category showing the highest proportion of impaired participants while displaying the strongest relationship between the MA and LA arms impairments (rs = 0.93). Feedback control was the unilateral performance category most often associated with impairments in bilateral tasks (6 out of 8 performance categories).

Conclusions

Adults with CP experienced more impairment in bilateral tasks while still having substantial impairments in unilateral tasks. They frequently display Feedforward control impairments combined with a higher reliance on Feedback control during both bilateral and unilateral tasks, leading to poorer motor performance.
Characterization of pathogenic genetic variants in Russian patients with primary ciliary dyskinesia using gene panel sequencing and transcript analysis
Authors: Zlotina Anna , Barashkova Svetlana , Zhuk Sergey , Skitchenko Rostislav , Usoltsev Dmitrii , Sokolnikova Polina , Artomov Mykyta , Alekseenko Svetlana , Simanova Tatiana , Goloborodko Maria , Berleva Olga , Kostareva Anna
Published: August 2024

Background

Primary ciliary dyskinesia (PCD) is a group of rare genetically heterogeneous disorders caused by defective cilia and flagella motility. The clinical phenotype of PCD patients commonly includes chronic oto-sino-pulmonary disease, infertility, and, in about half of cases, laterality defects due to randomization of left–right body asymmetry. To date, pathogenic variants in more than 50 genes responsible for motile cilia structure and assembly have been reported in such patients. While multiple population-specific mutations have been described in PCD cohorts from different countries, the data on genetic spectrum of PCD in Russian population are still extremely limited.

Results

The present study provides a comprehensive clinical and genetic characterization of 21 Russian families with PCD living in various country regions. Anomalies of ciliary beating in patients` respiratory epithelial cells were confirmed by high-speed video microscopy. In the most cases, custom-designed panel sequencing allowed to uncover causative variants in well-known or rarely mentioned PCD-related genes, including DNAH5, DNAH11, CFAP300, LRRC6, ZMYND10, CCDC103, HYDIN, ODAD4, DNAL1, and OFD1. The variations comprised common mutations, as well as novel genetic variants, some of which probably specific for Russian patients. Additional targeted analysis of mRNA transcripts from ciliated cells enabled us to specify functional effects of newly identified genetic variants in DNAH5 (c.2052+3G>T, c.3599-2A>G), HYDIN (c.10949-2A>G, c.1797C>G), and ZMYND10 (c.510+1G>C) on splicing process. In particular, the splice site variant c.2052+3G>T, detected in four unrelated families, resulted in skipping of exon 14 in DNAH5 transcripts and, according to haplotype analysis of affected probands, was proposed as an ancestral founder mutation in Udmurt population.

Conclusions

The reported data provide a vital insight into genetic background of primary ciliary dyskinesia in the Russian population. The findings clearly illustrate the utility of gene panel sequencing coupled with transcriptional analysis in identification and clinical interpretation of novel genetic variants.
Changes in urinary renal injury markers in children with Mycoplasma pneumoniae pneumonia and a prediction model for related early renal injury
Authors: Zhang Ju , Ma He-kai , Li Bao-wen , Ma Ke-Ke , Zhang Yu-Ling , Li Shu-jun
Published: August 2024

Background

This study aims to analyse changes in urinary kidney injury markers in children with Mycoplasma pneumoniae pneumonia (MPP), investigate the risk factors for MPP-related acute kidney injury (AKI) and establish a model to predict MPP-related AKI.

Methods

Ninety-five children were enrolled based on the study’s inclusion and exclusion criteria. They were divided into a severe MPP (SMPP) group and a non-SMPP group and then into an AKI group and a non-AKI group according to the presence of AKI. A univariate logistic regression analysis was performed to explore the early risk factors for AKI. Based on a multivariate logistic regression analysis and a least absolute shrinkage and selection operator regression analysis, appropriate variables were selected to establish a prediction model, and R 4.2.2 software was used to draw nomograms and generate a dynamic nomogram website.

Results

Seven urinary kidney injury markers were abnormally elevated in the SMPP group and the non-SMPP group: urinary N-acetyl-β-D-glucosaminidase (NAG), β2-microglobulin, α1-microglobulin, retinol-binding protein, urinary immunoglobulin G, urinary transferrin and urinary microalbumin. Sixteen children were identified with AKI during hospitalisation. The AKI group had higher levels of urinary NAG, α1-microglobulin, β2-microglobulin, urinary microalbumin, urinary transferrin and retinol-binding protein than the non-AKI group (P < 0.05). The MPP-related AKI prediction model consists of four indicators (serum immunoglobulin M [IgM], C-reactive protein [CRP], urine NAG and sputum plug presence) and a dynamic nomogram.

Conclusion

Urinary kidney injury markers are often elevated in children with MPP; urinary NAG is the marker most likely to be elevated, and it is especially evident in severe cases. The nomogram of the prediction model, comprising serum IgM, CRP, urinary NAG and sputum plug presence, can predict the probability of AKI in children with MPP.
Integrated prenatal and postnatal management for neonates with transposition of the great arteries: thirteen-year experience at a single center
Authors: Lin Xieyi , Huang Ying , Xie Wen , Chen Lu , Huang Yuping , Huang Yu , Ma Bingyu , Wen Shusheng , Pan Wei
Published: August 2024

Background

Transposition of the great arteries (TGA) is the most common cyanotic congenital heart defect in neonates but with low prenatal detection rate. This study sought to review the prenatal diagnosis, associated abnormalities, and mid-term postnatal outcomes of fetuses with TGA and investigate the integrated prenatal and postnatal management for TGA neonates.

Methods

A total of 134 infants prenatally diagnosed with TGA in Guangdong Provincial People’s Hospital, China, from January 2009 to December 2022 were included in the study. The prenatal ultrasound data and neonatal records were reviewed to assess the accuracy of prenatal diagnosis. Univariate and multivariate logistic and Cox analyses were used to identify risk factors associated with prognosis in such individuals.

Results

The population originated from 40 cities in 10 provinces in China, with integrated antenatal and postnatal management rate reaching 94.0% (126/134) and a high accuracy rate (99.3%) of prenatal primary diagnosis. The median period of follow-up was 1.6 [interquartile range (IQR) 0.1–4.3] years. There were 3 (2.2%) postnatal deaths, 118 (88.1%) patients undergoing arterial switch operation (ASO), 3 (2.2%) undergoing Rastelli operations and 5 (3.7%) doing stage operations. Of 118 patients receiving ASO, the major morbidity occurred in 64 patients (54.2%), and right ventricular outflow tract obstruction (RVOTO) in 31 (26.3%). In the multivariate logistic analysis, gestational ages at birth (OR = 0.953, 95% CI 0.910–0.991; p = 0.025) and cardiopulmonary bypass (CPB) time (OR = 1.010, 95% CI 1.000–1.030; p = 0.038) were identified as independent risk factors associated with major morbidity. In the Cox multivariate analysis, aortic cross-clamping time (HR = 1.030, 95% CI 1.000–1.050; p = 0.017) was identified as independent risk factor associated with RVOTO.

Conclusion

Earlier gestational ages at birth and longer CPB time are significantly associated with increased morbidity. Integrated prenatal and postnatal management is recommended for patients with prenatal diagnosis of TGA.
Real-time identification of epistatic interactions in SARS-CoV-2 from large genome collections
Authors: Innocenti Gabriel , Obara Maureen , Costa Bibiana , Jacobsen Henning , Katzmarzyk Maeva , Cicin-Sain Luka , Kalinke Ulrich , Galardini Marco
Published: August 2024

Background

The emergence of the SARS-CoV-2 virus has highlighted the importance of genomic epidemiology in understanding the evolution of pathogens and guiding public health interventions. The Omicron variant in particular has underscored the role of epistasis in the evolution of lineages with both higher infectivity and immune escape, and therefore the necessity to update surveillance pipelines to detect them early on.

Results

In this study, we apply a method based on mutual information between positions in a multiple sequence alignment, which is capable of scaling up to millions of samples. We show how it can reliably predict known experimentally validated epistatic interactions, even when using as little as 10,000 sequences, which opens the possibility of making it a near real-time prediction system. We test this possibility by modifying the method to account for the sample collection date and apply it retrospectively to multiple sequence alignments for each month between March 2020 and March 2023. We detected a cornerstone epistatic interaction in the Spike protein between codons 498 and 501 as soon as seven samples with a double mutation were present in the dataset, thus demonstrating the method’s sensitivity. We test the ability of the method to make inferences about emerging interactions by testing candidates predicted after March 2023, which we validate experimentally.

Conclusions

We show how known epistatic interaction in SARS-CoV-2 can be detected with high sensitivity, and how emerging ones can be quickly prioritized for experimental validation, an approach that could be implemented downstream of pandemic genome sequencing efforts.
Enhanced extracellular production of maltotetraose amylase from Pseudomonas saccharophila in Bacillus subtilis through regulatory element optimization
Authors: Cong Guilong , Li Mingyu , Dong Sitong , Ai Teng , Ren Xiaopeng , Li Xianzhen , Wang Conggang , Yang Fan
Published: August 2024

Maltotetraose amylase (Mta) catalyzes the hydrolysis of amylaceous polysaccharides into maltotetraose, which is an important functional sugar used in the food industry. However, the lack of efficient expression systems for recombinant Mta has hindered its scale-up production and application. In this study, a codon-optimized mta gene from Pseudomonas saccharophila was efficiently produced in Bacillus subtilis by optimizing the regulatory elements. First, a plasmid library containing 173 different signal peptide sequences placed upstream of mta gene was constructed, and transformed into B. subtilis strain WB800N(amyEΔ1) for high-throughput screening. The signal peptide yhcR was found to significantly enhance the secretion of Mta, reaching an activity of 75.4 U/mL in the culture medium. After optimization of the promoters, the Mta activity was further increased to 100.3 U/mL using a dual-promoter PHpaIIPamyE. Finally, the carbon sources and nitrogen sources for recombinant Mta production were optimized, yielding a highest Mta activity of 288.9 U/mL under the optimal culture conditions. The crude enzyme solution containing recombinant Mta produced a highest maltotetraose yield of 70.3% with 200 g/L of maltodextrin as the substrate. Therefore, the present study have demonstrated a high yield of Mta produced in B. subtilis, laying the foundation for large-scale Mta production and application.
Problematic anger among military personnel after combat deployment: prevalence and risk factors
Authors: Nordstrand Andreas Espetvedt , Anyan Frederick , Bøe Hans Jakob , Hjemdal Odin , Noll Laura Katherine , Reichelt Jon Gerhard , Forbes David , Adler Amy B.
Published: August 2024

Background

Problematic anger, characterized by excessive frequency, intensity, and duration of anger which causes substantial emotional distress and functional interference, poses a marked challenge in military populations. Despite its importance, research on this topic is limited. This study contributes to the literature by exploring problematic anger in a large sample of Norwegian military personnel who served in NATO missions in Afghanistan.

Methods

All Norwegian military personnel who deployed to Afghanistan between 2001 and 2020 were sent a link to a cross-sectional web-based survey by the Joint Medical Services of the Norwegian Armed Forces in 2020. A total of 6205 individuals (response rate: 67.7%) participated. The cross-sectional survey assessed problematic anger, mental and physical health, war zone stressor exposure, and quality of life.

Results

Overall, 8.4% of participants reported problematic anger. Mental health disorders, deployment-related shame and guilt, chronic pain, and challenges with the military-to-civilian transition were independently associated with problematic anger. Both staying in service and maintaining a part-time connection with the military as a reservist mitigated the risk of problematic anger after deployment, compared to complete separation from military service.

Conclusion

Findings demonstrate a sizeable prevalence of problematic anger among veterans of combat deployments. Given the associations between problematic anger and mental health disorders, chronic pain, and transition challenges, interventions designed to mitigate problematic anger need to be multi-faceted, including the possibility of maintaining an ongoing connection to military service. By reducing the risk of problematic anger, occupational, interpersonal and health outcomes may be improved for service members. Future research should examine the impact of problematic anger on adjustment over time, prevention strategies, and problematic anger in other high-risk occupations.
CAR Macrophages: a promising novel immunotherapy for solid tumors and beyond
Authors: Lu Jialin , Ma Yuqing , Li Qiuxin , Xu Yihuan , Xue Yiquan , Xu Sheng
Published: August 2024

With the advent of adoptive cellular therapy, chimeric antigen receptor (CAR)-T cell therapy has gained widespread application in cancer treatment and has demonstrated significant efficacy against certain hematologic malignancies. However, due to the limitations of CAR-T cell therapy in treating solid tumors, other immune cells are being modified with CAR to address this issue. Macrophages have emerged as a promising option, owing to their extensive immune functions, which include antigen presentation, powerful tumor phagocytosis, and particularly active trafficking to the tumor microenvironment. Leveraging their unique advantages, CAR-macrophages (CAR-M) are expected to enhance the effectiveness of solid tumor treatments as a novel form of immunotherapy, potentially overcoming major challenges associated with CAR-T/NK therapy. This review outlines the primary mechanism underlying CAR-M and recent progressions in CAR-M therapy, while also discussing their further applications.
Oral nicotinamide provides robust, dose-dependent structural and metabolic neuroprotection of retinal ganglion cells in experimental glaucoma
Authors: Cimaglia Gloria , Tribble James R. , Votruba Marcela , Williams Pete A. , Morgan James E.
Published: August 2024

A compromised capacity to maintain NAD pools is recognized as a key underlying pathophysiological feature of neurodegenerative diseases. NAD acts as a substrate in major cell functions including mitochondrial homeostasis, cell signalling, axonal transport, axon/Wallerian degeneration, and neuronal energy supply. Dendritic degeneration is an early marker of neuronal stress and precedes cell loss. However, little is known about dendritic structural preservation in pathologic environments and remodelling in mature neurons. Retinal ganglion cell dendritic atrophy is an early pathological feature in animal models of the disease and has been demonstrated in port-mortem human glaucoma samples. Here we report that a nicotinamide (a precursor to NAD through the NAD salvage pathway) enriched diet provides robust retinal ganglion cell dendritic protection and preserves dendritic structure in a rat model of experimental glaucoma. Metabolomic analysis of optic nerve samples from the same animals demonstrates that nicotinamide provides robust metabolic neuroprotection in glaucoma. Advances in our understanding of retinal ganglion cell metabolic profiles shed light on the energetic shift that triggers early neuronal changes in neurodegenerative diseases. As nicotinamide can improve visual function short term in existing glaucoma patients, we hypothesize that a portion of this visual recovery may be due to dendritic preservation in stressed, but not yet fully degenerated, retinal ganglion cells.
Multi-objective optimization and long-time simulation of a multi-borehole ground heat exchanger system
Authors: Sarshar Saghar , Gharali Kobra , Saffaripour Meghdad , Nathwani Jatin , Dusseault Maurice B.
Published: August 2024

Multi-objective optimization and CFD simulation are conducted to optimize the design of a multi-borehole ground heat exchanger (GHE) system and assess its long-time performance. The multi-objective optimization is performed to minimize the entropy generation number (EGN) and total cost rate by using various evolutionary algorithms, including NSGA-II, GDE-3, MOEA/D, PESA-II, SPEA-II, and SMPSO. NSGA-II and GDE-3 algorithms perform best in obtaining Pareto optimal solutions. Three prominent points on the NSGA-II Pareto frontier, representing the results of single-objective thermodynamic, single-objective economic, and multi-objective optimizations, are simulated in three dimensions over three months. The trends of EGN variations extracted from the transient CFD simulation agree well with those from the steady analytical model. The EGN obtained from multi-objective optimization is 58.8% lower than the EGN obtained using single-objective economic optimization and 1.9 times higher than that calculated from single-objective thermodynamic optimization. Likewise, the total cost rate obtained from multi-objective optimization is 64.4% lower than the value obtained from single-objective thermodynamic optimization and four times higher than that calculated using single-objective economic optimization. The proposed optimization approach can be reliably applied to improve the design of multi-borehole GHE systems.