bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with health professionals’ stress reactions, job satisfaction, intention to leave and health-related outcomes in acute care, rehabilitation and psychiatric hospitals, nursing homes and home care organisations
Authors: Peter Karin Anne , Voirol Christian , Kunz Stefan , Gurtner Andrea , Renggli Fabienne , Juvet Typhaine , Golz Christoph
Published: March 2024

The aim of this study is to identify (1) the extent of work-related stress and (2) stressors associated with cognitive and behavioral stress reactions, burnout symptoms, health status, quality of sleep, job satisfaction, and intention to leave the organization and the profession among health professionals working in acute care /rehabilitation hospitals, psychiatric hospitals, nursing homes, and home care organizations.

Background

Health professionals are faced with various stressors at work and as a consequence are leaving their profession prematurely. This study aimed to identify the extent of work-related stress and stressors associated with stress reactions, job satisfaction, and intention to leave and health-related outcomes among health professionals working in different healthcare sectors (acute care, rehabilitation and psychiatric hospitals, nursing homes and home care organizations).

Methods

This study is based on a repeated cross-sectional design, which includes three data measures between 2017 and 2020 and 19,340 participating health professionals from 26 acute care / rehabilitation hospitals, 12 psychiatric hospitals, 86 nursing homes and 41 home care organizations in Switzerland. For data analysis, hierarchical multilevel models (using AIC) were calculated separately for hospitals, nursing homes, and home care organizations, regarding health professionals’ stress symptoms, job satisfaction, intention to leave the organization / profession, general health status, burnout symptoms, and quality of sleep.

Results

The main findings reveal that the incompatibility of health professionals’ work and private life was significantly associated (p < 0.05) with their stress reactions, job satisfaction, intention to leave, and health-related outcomes in all the included work areas. The direct supervisor’s good leadership qualities were also associated with health professionals’ job satisfaction regarding all work areas (B ≥ 0.22, p = 0.000). In addition, a positive perceived bond with the organization (B ≥ 0.13, p < 0.01) and better development opportunities (B ≥ 0.05, p < 0.05) were associated with higher job satisfaction and a lower intention to leave the organization and profession among health professionals. Also, a younger age of health professionals was associated with a higher intention to leave the organization and the profession prematurely in all the included work areas. High physical (B ≥ 0.04, p < 0.05) and quantitative demands (B ≥ 0.05, p = 0.000) at work were also associated with negative health-related outcomes.
Dose-response relationship between lung function and chest imaging response to silica exposures in artificial stone manufacturing workers
Authors: Chen Chi-Hsien , Tsai Perng-Jy , Chang Wen-Wen , Chen Cheng-Yao , Chen Chih-Yong , Yates Deborah , Guo Yue Leon
Published: March 2024

Background

Occupational exposure to artificial stone, a popular material used for countertops, can cause accelerated silicosis, but the precise relationship between silica dose and disease development is unclear.

Objectives

This study evaluated the impact of silica exposure on lung function and chest imaging in artificial stone manufacturing workers.

Methods

Questionnaire and spirometry assessments were administered to workers in two plants. A high-exposure subset underwent further evaluation, including chest CT and DLco. Weighting factors, assigned as proxies for silica exposure, were based on work tasks. Individual cumulative exposures were estimated using area concentration measurements and time spent in specific areas. Exposure-response associations were analyzed using linear and logistic regression models.

Results

Among 65 participants, the mean cumulative silica exposure was 3.61 mg/m3-year (range 0.0001 to 44.4). Each 1 mg/m3-year increase was associated with a 0.46% reduction in FVC, a 0.45% reduction in FEV1, and increased lung function abnormality risk (aOR = 1.27, 95% CI = 1.03–1.56). Weighting factors correlated with cumulative exposures (Spearman correlation = 0.59, p < 0.0001), and weighted tenure was associated with lung function abnormalities (aOR = 1.04, 95% CI = 1.01–1.09). Of 37 high-exposure workers, 19 underwent chest CT, with 12 (63%) showing abnormal opacities. Combining respiratory symptoms, lung function, and chest X-ray achieved 91.7% sensitivity and 75% specificity for predicting chest CT abnormalities.

Conclusion

Lung function and chest CT abnormalities occur commonly in artificial stone workers. For high-exposure individuals, abnormalities on health screening could prompt further chest CT examination to facilitate early silicosis detection.
Towards more realistic measures of accessibility to emergency departments in Sweden
Authors: Hassler Jacob , Andersson Granberg Tobias , Steins Krisjanis , Ceccato Vania
Published: March 2024

Background

Assuring that emergency health care (EHC) is accessible is a key objective for health care planners. Conventional accessibility analysis commonly relies on resident population data. However, the allocation of resources based on stationary population data may lead to erroneous assumptions of population accessibility to EHC.

Method

Therefore, in this paper, we calculate population accessibility to emergency departments in Sweden with a geographical information system based network analysis. Utilizing static population data and dynamic population data, we investigate spatiotemporal patterns of how static population data over- or underestimates population sizes derived from temporally dynamic population data.

Results

Our findings show that conventional measures of population accessibility tend to underestimate population sizes particularly in rural areas and in smaller ED’s catchment areas compared to urban, larger ED’s—especially during vacation time in the summer.

Conclusions

Planning based on static population data may thus lead to inequitable distributions of resources. This study is motivated in light of the ongoing centralization of ED’s in Sweden, which largely depends on population sizes in ED’s catchment areas.
The effects of restraint stress on ceramide metabolism disorders in the rat liver: the role of CerS6 in hepatocyte injury
Authors: Liu Yichang , Sun Zhaoling , Sun Qiuli , Wang Li , Wang Chuan , Li Yingmin , Ma Chunling , Shi Weibo , Zhang Guozhong , Dong Yiming , Zhang Xiaojing , Cong Bin
Published: March 2024

Background

Stress is implicated in various pathological conditions leading to liver injury. Existing evidence suggests that excessive stress can induce mitochondrial damage in hepatocytes, yet the underlying mechanism remains unclear. Ceramide synthase 6 (CerS6)-derived C16:0 ceramide is recognised as a lipotoxic substance capable of causing mitochondrial damage. However, the role of CerS6 in stress has received insufficient attention. This study aimed to explore the involvement of CerS6 in stress-induced hepatic damage and its associated mechanisms.

Methods

The rat restraint stress model and a corticosterone (CORT)-induced hepatocyte stress model were employed for in vivo and in vitro experimental analyses, respectively. Changes in mitochondrial damage and ceramide metabolism in hepatocytes induced by stress were evaluated. The impact of CORT on mitochondrial damage and ceramide metabolism in hepatocytes was assessed following CerS6 knockdown. Mitochondria were isolated using a commercial kit, and ceramides in liver tissue and hepatocytes were detected by LC–MS/MS.

Results

In comparison to the control group, rats subjected to one week of restraint exhibited elevated serum CORT levels. The liver displayed significant signs of mitochondrial damage, accompanied by increased CerS6 and mitochondrial C16:0 ceramide, along with activation of the AMPK/p38 MAPK pathway. In vitro studies demonstrated that CORT treatment of hepatocytes resulted in mitochondrial damage, concomitant with elevated CerS6 and mitochondrial C16:0 ceramide. Furthermore, CORT induced sequential phosphorylation of AMPK and p38 MAPK proteins, and inhibition of the p38 MAPK pathway using SB203580 mitigated the CORT-induced elevation in CerS6 protein. Knocking down CerS6 in hepatocytes inhibited both the increase in C16:0 ceramide and the release of mitochondrial cytochrome c induced by CORT.

Conclusions

CerS6-associated C16:0 ceramide plays a mediating role in stress-induced mitochondrial damage in hepatocytes. The molecular mechanism is linked to CORT-induced activation of the AMPK/p38 MAPK pathway, leading to upregulated CerS6.
Conditional generative adversarial network driven radiomic prediction of mutation status based on magnetic resonance imaging of breast cancer
Authors: Huang Zi Huai , Chen Lianghong , Sun Yan , Liu Qian , Hu Pingzhao
Published: March 2024

Background

Breast Cancer (BC) is a highly heterogeneous and complex disease. Personalized treatment options require the integration of multi-omic data and consideration of phenotypic variability. Radiogenomics aims to merge medical images with genomic measurements but encounter challenges due to unpaired data consisting of imaging, genomic, or clinical outcome data. In this study, we propose the utilization of a well-trained conditional generative adversarial network (cGAN) to address the unpaired data issue in radiogenomic analysis of BC. The generated images will then be used to predict the mutations status of key driver genes and BC subtypes.

Methods

We integrated the paired MRI and multi-omic (mRNA gene expression, DNA methylation, and copy number variation) profiles of 61 BC patients from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). To facilitate this integration, we employed a Bayesian Tensor Factorization approach to factorize the multi-omic data into 17 latent features. Subsequently, a cGAN model was trained based on the matched side-view patient MRIs and their corresponding latent features to predict MRIs for BC patients who lack MRIs. Model performance was evaluated by calculating the distance between real and generated images using the Fréchet Inception Distance (FID) metric. BC subtype and mutation status of driver genes were obtained from the cBioPortal platform, where 3 genes were selected based on the number of mutated patients. A convolutional neural network (CNN) was constructed and trained using the generated MRIs for mutation status prediction. Receiver operating characteristic area under curve (ROC-AUC) and precision-recall area under curve (PR-AUC) were used to evaluate the performance of the CNN models for mutation status prediction. Precision, recall and F1 score were used to evaluate the performance of the CNN model in subtype classification.

Results

The FID of the images from the well-trained cGAN model based on the test set is 1.31. The CNN for TP53, PIK3CA, and CDH1 mutation prediction yielded ROC-AUC values 0.9508, 0.7515, and 0.8136 and PR-AUC are 0.9009, 0.7184, and 0.5007, respectively for the three genes. Multi-class subtype prediction achieved precision, recall and F1 scores of 0.8444, 0.8435 and 0.8336 respectively. The source code and related data implemented the algorithms can be found in the project GitHub at https://github.com/mattthuang/BC_RadiogenomicGAN.

Conclusion

Our study establishes cGAN as a viable tool for generating synthetic BC MRIs for mutation status prediction and subtype classification to better characterize the heterogeneity of BC in patients. The synthetic images also have the potential to significantly augment existing MRI data and circumvent issues surrounding data sharing and patient privacy for future BC machine learning studies.
Th17/1 and ex-Th17 cells are detected in patients with polyarticular juvenile arthritis and increase following treatment
Authors: Wood Stephanie , Branch Justin , Vasquez Priscilla , DeGuzman Marietta M. , Brown Amanda , Sagcal-Gironella Anna Carmela , Singla Saimun , Ramirez Andrea , Vogel Tiphanie P.
Published: March 2024

Background

A better understanding of the pathogenesis of polyarticular juvenile idiopathic arthritis (polyJIA) is needed to aide in the development of data-driven approaches to guide selection between therapeutic options. One inflammatory pathway of interest is JAK-STAT signaling. STAT3 is a transcription factor critical to the differentiation of inflammatory T helper 17 cells (Th17s). Previous studies have demonstrated increased STAT3 activation in adult patients with rheumatoid arthritis, but less is known about STAT3 activation in polyJIA. We hypothesized that Th17 cells and STAT3 activation would be increased in treatment-naïve polyJIA patients compared to pediatric controls.

Methods

Blood from 17 patients with polyJIA was collected at initial diagnosis and again if remission was achieved (post-treatment). Pediatric healthy controls were also collected. Peripheral blood mononuclear cells were isolated and CD4 + T cell subsets and STAT activation (phosphorylation) were evaluated using flow cytometry. Data were analyzed using Mann–Whitney U and Wilcoxon matched-pairs signed rank tests.

Results

Treatment-naïve polyJIA patients had increased Th17 cells (CD3 + CD4 + interleukin(IL)-17 +) compared to controls (0.15% v 0.44%, p < 0.05), but Tregs (CD3 + CD4 + CD25 + FOXP3 +) from patients did not differ from controls. Changes in STAT3 phosphorylation in CD4 + T cells following ex vivo stimulation were not significantly different in patients compared to controls. We identified dual IL-17 + and interferon (IFN)γ + expressing CD4 + T cells in patients, but not controls. Further, both Th17/1 s (CCR6 + CD161 + IFNγ + IL-17 +) and ex-Th17s (CCR6 + CD161 + IFNγ + IL-17neg) were increased in patients’ post-treatment (Th17/1: 0.3% v 0.07%, p < 0.05 and ex-Th17s: 2.3% v 1.4%, p < 0.05). The patients with the highest IL-17 expressing cells post-treatment remained therapy-bound.

Conclusions

Patients with polyJIA have increased baseline Th17 cells, potentially reflecting higher tonic STAT3 activation in vivo. These quantifiable immune markers may identify patients that would benefit upfront from pathway-focused biologic therapies. Our data also suggest that inflammatory CD4 + T cell subsets not detected in controls but increased in post-treatment samples should be further evaluated as a tool to stratify patients in remission on medication. Future work will explore these proposed diagnostic and prognostic biomarkers.
Effects of the powerball® system on muscle strength, coordination, fatigue, functionality and quality of life in people with multiple sclerosis. A randomized clinical trial
Authors: Blázquez-Fernández Aitor , López-Hazas-Jiménez Gemma , Fernández-Vázquez Diego , Navarro-López Víctor , Fernández-González Pilar , Marcos-Antón Selena , Molina-Rueda Francisco , Cano-de-la-Cuerda Roberto
Published: March 2024

Introduction

Although clinical and functional impairments in the lower limbs have been extensively studied in patients with MS, the upper limb (UL) are also frequently affected. Clinical impairment of the UL in patients with MS is very common with muscle strength and hand dexterity as critical factors in maintaining functional activities that are the basis for independence and quality of life in people with MS.

Objective

To investigate the effects of a training protocol using the Powerball® system in combination with conventional physiotherapy on muscle strength, coordination, fatigue, functionality, and quality of life in persons with MS over an 8-week period.

Materials and methods

A double-blind randomized controlled trial was conducted. The control group received conventional treatment, while the experimental group received additional UL training using the Powerball® system. Both groups received the same number of sessions and weeks of intervention. The following outcome measures were used: isometric grip and pinch strength, Box and Block Test (BBT), Nine Hole Peg Test (NHPT), Abilhand scale, Fatigue Severity Scale (FSS), Multiple Sclerosis Impact Scale (MSIS-29), and Likert satisfaction questionnaire for the experimental group. All measures were administered at baseline, after the treatment, and during a 3-week follow-up period.

Results

25 patients completed the study (12 in the experimental and 13 in the control group). The experimental group showed significant improvements in coordination and manual dexterity of the more affected UL as measured by the BBT comparing pre- to post-treatment (p = 0.048) and pre-treatment to follow-up (p = 0.001), and on the less affected UP comparing pre-treatment to follow-up (p < 0.001) and post-treatment to follow-up (p = 0.034). The Likert-type satisfaction questionnaire obtained a mean score of 89.10 (± 8.54) out of 100 points.

Conclusions

Upper limb treatment protocol using the Powerball® system, in combination with conventional physiotherapy for 8 weeks resulted in significant improvements in the intra-group analysis for UL coordination and manual dexterity in favor of the experimental group. The experimental group showed excellent satisfaction to the treatment.
PKM2 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating epithelial-mesenchymal transition: an experimental research
Authors: Zhou Xin , Li Yanshi , Pan Min , Lu Tao , Liu Chuan , Wang Zhihai , Tang Fengxiang , Hu Guohua
Published: March 2024

Background

Patients with hypopharyngeal carcinoma (HPC) have a poor prognosis mainly because of lymphatic metastasis. This research aimed to determine the PKM2 role in lymphatic metastasis in HPC and the underlying molecular mechanism contributing to this phenomenon.

Methods

PKM2 in HPC was studied for its expression and its likelihood of overall survival using TCGA dataset. Western blotting, qRT-PCR, and IHC were employed to confirm PKM2 expression. Methods including gain- and loss-of-function were used to examine the PKM2 role in HPC metastasis in vitro and in vivo. In vitro and in vivo studies also confirmed lymphatic metastasis’s mechanism.

Results

Prominent PKM2 overexpression was seen in patients with lymphatic metastasis of HPC, and there was an inherent relationship between a high PKM2 level and poor prognosis. In vitro research showed that knocking down PKM2 decreased tumor cell invasion, migration, and proliferation while promoting apoptosis and inhibiting epithelial-mesenchymal transition, but overexpressing PKM2 had the reverse effect. Animal studies suggested that PKM2 may facilitate tumor development and lymphatic metastasis.

Conclusions

Our findings suggest that PKM2 may be a tumor’s promoter gene of lymphatic metastasis, which may promote lymphatic metastasis of HPC by regulating epithelial-mesenchymal transition. PKM2 may be a biomarker of metastatic potential, ultimately providing a basis for exploring new therapeutic targets.
Black carbon in urban soils: land use and climate drive variation at the surface
Authors: Burke Molly , Marín-Spiotta Erika , Ponette-González Alexandra G.
Published: March 2024

Background

Black carbon (BC) encompasses a range of carbonaceous materials––including soot, char, and charcoal––derived from the incomplete combustion of fossil fuels and biomass. Urban soils can become enriched in BC due to proximity to these combustion sources. We conducted a literature review of BC in urban soils globally and found 26 studies reporting BC and total organic carbon (TOC) content collected to a maximum of 578 cm depth in urban soils across 35 cities and 10 countries. We recorded data on city, climate, and land use/land cover characteristics to examine drivers of BC content and contribution to TOC in soil.

Results

All studies were conducted in the northern hemisphere, with 68% of the data points collected in China and the United States. Surface samples (0–20 cm) accounted for 62% of samples in the dataset. Therefore, we focused our analysis on 0–10 cm and 10–20 cm depths. Urban soil BC content ranged from 0–124 mg/g (median = 3 mg/g) at 0–10 cm and from 0–53 mg/g (median = 2.8 mg/g) at 10–20 cm depth. The median proportional contribution of BC to TOC was 23% and 15% at 0–10 cm and 10–20 cm, respectively. Surface soils sampled in industrial land use and near roads had the highest BC contents and proportions, whereas samples from residential sites had among the lowest. Soil BC content decreased with mean annual soil temperature.

Conclusions

Our review indicates that BC comprises a major fraction (nearly one quarter) of the TOC in urban surface soils, yet sampling bias towards the surface could hide the potential for BC storage at depth. Land use emerged as an importer driver of soil BC contents and proportions, whereas land cover effects remain uncertain. Warmer and wetter soils were found to have lower soil BC than cooler and drier soils, differences that likely reflect soil BC loss mechanisms. Additional research on urban soil BC at depth and from diverse climates is critical to better understand the role of cities in the global carbon cycle.
Cox proportional hazard-model application: time to cervical cancer screening among women living with HIV in South Africa
Authors: Hollington Marcus
Published: March 2024

Background

There is an increased risk of cervical cancer among women living with HIV. While studies have long examined the association between cervical cancer among women with HIV, no study has examined the time taken for women with HIV to undergo cervical cancer screening as well as the hazard thereof in South Africa.

Methods

The study used cross-sectional data from the 2016 South Africa Demographic and Health Survey. To allow for longitudinal analysis and to address the issue of right-censoring, the data were reformatted to a person-data file. The selection criteria were limited to women living with HIV (WLHIV) who had also responded to the question on cervical cancer screening. Descriptive statistics were employed to show the levels of HIV among women aged 15 and older in South Africa. Additionally, Kaplan‒Meier curves were employed to investigate the time to CCS by WLHIV in South Africa. Thereafter, an unadjusted Cox hazards regression model was employed to examine the hazard of undergoing CCS among WLHIV. Finally, it employed an adjusted model to examine the hazard of CCS among WLHIV while adjusting for other factors.

Results

Nineteen percent (n = 1,159) of the women who participated in the study tested positive for HIV. Herein, it was found that the risk of CCS among WLHIV began at the age of approximately 19 years. Thereafter, the hazard of undergoing CCS among WLHIV began to decrease at 58 years. There was a significant association between CCS and WLHIV. Additionally, several covariates were found to be significantly associated with HIV. These were race, province, area of residence, marriage, educational attainment, employment, alcohol consumption, perceived health perception, and health insurance.

Conclusion

The hazard of CCS was lower among WLHIV compared to WLHIV who did not undergo CCS in South Africa. This puts HIV-positive women at risk of increased morbidity and mortality from potential cervical cancer and HIV comorbidity due to CCS deficits within this group. This is because they are susceptible to HPV and subsequent cervical cancer due to a compromised immune system. HIV-positive women need to routinely undergo CCS every 12 months from baseline for 3 years. Thereafter, they should undergo CCS once every 3 years to reduce their risk of developing the disease.
Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study
Authors: Chen Geng-dong , Li Peng-sheng , Zhou Zi-xing , Wang Hai-yan , Gou Xiao-yan , Ye Shao-xin , Lin Dong-xin , Fan Da-zhi , Wang Li-juan , Liu Zheng-ping
Published: March 2024

Background

Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators.

Methods

A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects’ blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records.

Results

After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with − 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively.

Conclusions

Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.
Contribution of Anopheles gambiae sensu lato mosquitoes to malaria transmission during the dry season in Djoumouna and Ntoula villages in the Republic of the Congo
Authors: Mbama Ntabi Jacques Dollon , Malda Bali Espoir Divin , Lissom Abel , Akoton Romaric , Djontu Jean Claude , Missontsa Georges , Mouzinga Freisnel Hermeland , Baina Marcel Tapsou , Djogbenou Luc , Ndo Cyrille , Wondji Charles , Adegnika Ayola Akim , Lenga Arsène , Borrmann Steffen , Ntoumi Francine
Published: March 2024

Background

Mosquitoes belonging to the Anopheles gambiae sensu lato complex play a major role in malaria transmission across Africa. This study assessed the relative importance of members of An. gambiae s.l. in malaria transmission in two rural villages in the Republic of the Congo.

Methods

Adult mosquitoes were collected using electric aspirators from June to September 2022 in Djoumouna and Ntoula villages and were sorted by taxa based on their morphological features. Anopheles gambiae s.l. females were also molecularly identified. A TaqMan-based assay and a nested polymerase chain reaction (PCR) were performed to determine Plasmodium spp. in the mosquitoes. Entomological indexes were estimated, including man-biting rate, entomological inoculation rate (EIR), and diversity index.

Results

Among 176 mosquitoes collected, An. gambiae s.l. was predominant (85.8%), followed by Culex spp. (13.6%) and Aedes spp. (0.6%). Three members of the An. gambiae s.l. complex were collected in both villages, namely An. gambiae sensu stricto (74.3%), Anopheles coluzzii (22.9%) and Anopheles arabiensis (2.8%). Three Plasmodium species were detected in An. gambiae s.s. and An. coluzzii (Plasmodium falciparum, P. malariae and P. ovale), while only P. falciparum and P. malariae were found in An. arabiensis. In general, the Plasmodium infection rate was 35.1% (53/151) using the TaqMan-based assay, and nested PCR confirmed 77.4% (41/53) of those infections. The nightly EIR of An. gambiae s.l. was 0.125 infectious bites per person per night (ib/p/n) in Djoumouna and 0.08 ib/p/n in Ntoula. The EIR of An. gambiae s.s. in Djoumouna (0.11 ib/p/n) and Ntoula (0.04 ib/p/n) was higher than that of An. coluzzii (0.01 and 0.03 ib/p/n) and An. arabiensis (0.005 and 0.0 ib/p/n).

Conclusions

This study provides baseline information on the dominant vectors and dynamics of malaria transmission in the rural areas of the Republic of the Congo during the dry season. In the two sampled villages, An. gambiae s.s. appears to play a predominant role in Plasmodium spp. transmission.

Graphical Abstract
Causal relationship between diabetes mellitus, glycemic traits and Parkinson’s disease: a multivariable mendelian randomization analysis
Authors: Wang Qitong , Cai Benchi , Zhong Lifan , Intirach Jitrawadee , Chen Tao
Published: March 2024

Background

Observational studies have indicated an association between diabetes mellitus (DM), glycemic traits, and the occurrence of Parkinson’s disease (PD). However, the complex interactions between these factors and the presence of a causal relationship remain unclear. Therefore, we aim to systematically assess the causal relationship between diabetes, glycemic traits, and PD onset, risk, and progression.

Method

We used two-sample Mendelian randomization (MR) to investigate potential associations between diabetes, glycemic traits, and PD. We used summary statistics from genome-wide association studies (GWAS). In addition, we employed multivariable Mendelian randomization to evaluate the mediating effects of anti-diabetic medications on the relationship between diabetes, glycemic traits, and PD. To ensure the robustness of our findings, we performed a series of sensitivity analyses.

Results

In our univariable Mendelian randomization (MR) analysis, we found evidence of a causal relationship between genetic susceptibility to type 1 diabetes (T1DM) and a reduced risk of PD (OR = 0.9708; 95% CI: 0.9466, 0.9956; P = 0.0214). In our multivariable MR analysis, after considering the conditions of anti-diabetic drug use, this correlation disappeared with adjustment for potential mediators, including anti-diabetic medications, insulin use, and metformin use.

Conclusion

Our MR study confirms a potential protective causal relationship between genetically predicted type 1 diabetes and reduced risk of PD, which may be mediated by factors related to anti-diabetic medications.
Cytogenetics investigation in 151 Brazilian infertile male patients and genomic analysis in selected cases: experience of 14 years in a public genetic service
Authors: Adriano Márcia Regina Gimenes , Bortolai Adriana , Madia Fabricia Andreia Rosa , da Silva Carvalho Gleyson Francisco , Nascimento Amom Mendes , Zanardo Evelin Aline , Wolff Beatriz Martins , Waisberg Jaques , Bos-Mikich Adriana , Kulikowski Leslie Domenici , Dias Alexandre Torchio
Published: March 2024

Objectives

Male infertility accounts for approximately 30% of cases of reproductive failure. The characterization of genetic variants using cytogenomic techniques is essential for the adequate clinical management of these patients. We aimed to conduct a cytogenetic investigation of numerical and structural rearrangements and a genomic study of Y chromosome microdeletions/microduplications in infertile men derived from a single centre with over 14 years of experience.

Results

We evaluated 151 infertile men in a transversal study using peripheral blood karyotypes and 15 patients with normal karyotypes through genomic investigation by multiplex ligation-dependent probe amplification (MLPA) or polymerase chain reaction of sequence-tagged sites (PCR-STS) techniques. Out of the 151 patients evaluated by karyotype, 13 presented chromosomal abnormalities: two had numerical alterations, and 11 had structural chromosomal rearrangements. PCR-STS detected a BPY2 gene region and RBMY2DP pseudogene region microdeletion in one patient. MLPA analysis allowed the identification of one patient with CDY2B_1 and CDY2B_2 probe duplications (CDY2B and NLGN4Y genes) and one patient with BPY2_1, BPY2_2, and BPY2_4 probe duplications (PRY and RBMY1J genes).
An EWAS of dementia biomarkers and their associations with age, African ancestry, and PTSD
Authors: Miller Mark W. , Wolf Erika J. , Zhao Xiang , Logue Mark W. , Hawn Sage E.
Published: March 2024

Background

Large-scale cohort and epidemiological studies suggest that PTSD confers risk for dementia in later life but the biological mechanisms underlying this association remain unknown. This study examined this question by assessing the influences of PTSD, APOE ε4 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers Aβ40, Aβ42, GFAP, NfL, and pTau-181 measured in plasma. Our primary hypothesis was that PTSD would be associated with elevated levels of these markers.

Methods

Analyses were based on data from a PTSD-enriched cohort of 849 individuals. We began by performing factor analyses of the biomarkers, the results of which identified a two-factor solution. Drawing from the ATN research framework, we termed the first factor, defined by Aβ40 and Aβ42, “Factor A” and the second factor, defined by GFAP, NfL and pTau-181, “Factor TN.” Next, we performed epigenome-wide association analyses (EWAS) of the two-factor scores. Finally, using structural equation modeling (SEM), we evaluated (a) the influence of PTSD, age, APOE ε4 genotype and other covariates on levels of the ATN factors, and (b) tested the mediating influence of the EWAS-significant DNAm loci on these associations.

Results

The Factor A EWAS identified one significant locus, cg13053408, in FANCD2OS. The Factor TN analysis identified 3 EWAS-significant associations: cg26033520 near ASCC1, cg23156469 in FAM20B, and cg15356923 in FAM19A4. The SEM showed age to be related to both factors, more so with Factor TN (β = 0.581, p < 0.001) than Factor A (β = 0.330, p < 0.001). Genotype-determined African ancestry was associated with lower Factor A (β = 0.196, p < 0.001). Contrary to our primary hypothesis, we found a modest negative bivariate correlation between PTSD and the TN factor scores (r = − 0.133, p < 0.001) attributable primarily to reduced levels of GFAP (r = − 0.128, p < 0.001).

Conclusions

This study identified novel epigenetic associations with ATN biomarkers and demonstrated robust age and ancestral associations that will be essential to consider in future efforts to develop the clinical applications of these tests. The association between PTSD and reduced GFAP, which has been reported previously, warrants further investigation.
Combined transplantation of hiPSC-NSC and hMSC ameliorated neuroinflammation and promoted neuroregeneration in acute spinal cord injury
Authors: Du Xiaofeng , Kong Desheng , Guo Ruiyun , Liu Boxin , He Jingjing , Zhang Jinyu , Amponsah Asiamah Ernest , Cui Huixian , Ma Jun
Published: March 2024

Background

Spinal cord injury (SCI) is a serious clinical condition that has pathological changes such as increased neuroinflammation and nerve tissue damage, which eventually manifests as fibrosis of the injured segment and the development of a spinal cord cavity leading to loss of function. Cell-based therapy, such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs) are promising treatment strategies for spinal cord injury via immunological regulation and neural replacement respectively. However, therapeutic efficacy is rare reported on combined transplantation of MSC and NSC in acute mice spinal cord injury even the potential reinforcement might be foreseen. Therefore, this study was conducted to investigate the safety and efficacy of co-transplanting of MSC and NSC sheets into an SCI mice model on the locomotor function and pathological changes of injured spinal cord.

Methods

To evaluate the therapeutic effects of combination cells, acute SCI mice model were established and combined transplantation of hiPSC-NSCs and hMSCs into the lesion site immediately after the injury. Basso mouse scale was used to perform the open-field tests of hind limb motor function at days post-operation (dpo) 1, 3, 5, and 7 after SCI and every week after surgery. Spinal cord and serum samples were collected at dpo 7, 14, and 28 to detect inflammatory and neurotrophic factors. Hematoxylin–eosin (H&E) staining, masson staining and transmission electron microscopy were used to evaluate the morphological changes, fibrosis area and ultrastructure of the spinal cord.

Result

M&N transplantation reduced fibrosis formation and the inflammation level while promoting the secretion of nerve growth factor and brain-derived neurotrophic factor. We observed significant reduction in damaged tissue and cavity area, with dramatic improvement in the M&N group. Compared with the Con group, the M&N group exhibited significantly improved behaviors, particularly limb coordination.

Conclusion

Combined transplantation of hiPSC-NSC and hMSC could significantly ameliorate neuroinflammation, promote neuroregeneration, and decrease spinal fibrosis degree in safe and effective pattern, which would be indicated as a novel potential cell treatment option.

Graphical abstract
Culture of Hoffa fat pad mesenchymal stem/stromal cells on microcarrier suspension in vertical wheel bioreactor for extracellular vesicle production
Authors: Otahal Alexander , Kramer Karina , Neubauer Markus , Gulová Slavomira , Lacza Zsombor , Nehrer Stefan , De Luna Andrea
Published: March 2024

Background

Mesenchymal stromal cells (MSCs) are increasingly employed in regenerative medicine approaches for their immunomodulatory and anti-inflammatory properties, which are encoded in their secretome including extracellular vesicles (EVs). The Hoffa fat pad (HFP) located infrapatellarly harbours MSCs that could assist in tissue homeostasis in osteoarthritic joints. Intraarticular injection therapies based on blood products could modulate the populations of released HFP-MSC-EVs in a quantitative manner.

Methods

To obtain amounts of HFP-MSC-derived EVs that allow pre-clinical evaluation, suitable EV production systems need to be developed. This work investigates the release of EVs from primary HFP-MSCs cultivated in a 3D environment using microcarrier suspension culture in a vertical wheel bioreactor in comparison to conventional 2D culture. To simulate an intraarticular blood product therapy, cultures were treated with citrate-anticoagulated platelet-rich plasma (CPRP) or hyperacute serum (hypACT) before EV collection. HFP-MSC-EVs are enriched via ultrafiltration and characterised via Western Blot, nanoparticle tracking analysis in scatter as well as fluorescence mode. EV potency was determined via RT-qPCR analysing the expression of type II and X collagen (COL2 and COL10), as well as inducible nitric oxide synthase (iNOS) in primary OA chondrocytes.

Results

Blood product supplementation elevated HFP-MSC metabolic activity as determined via XTT assay over the course of 14 days. 3D culture resulted in a roughly 100-fold EV yield compared to 2D culture and elevated number of EVs released per cell. Total protein content correlated with the EV concentration. While typical EV marker proteins such as CD9, CD63 or Alix were detected in total protein extracts, CD9 and CD73 colocalised on individual EVs highlighting their cell origin. The type of blood product treatment did not affect the size or concentration of EVs obtained from HFP-MSCs. Assessing potency of 3D culture EVs in comparison to 2D EVs revealed superior biological activity with regard to inhibition of inflammation, inhibition of chondrocyte hypertrophy and induction of cartilage-specific ECM production.

Conclusions

HFP-MSCs proliferate in presence of human blood products indicating that animal serum in culture media can be avoided in the future. The culture of HFP-MSCs in the employed bioreactor was successfully used to generate quantities of EVs that could allow evaluation of HFP-MSC-EV-mediated effects in pre-clinical settings. In addition, EV potency of 3D EVs is superior to EVs obtained in conventional 2D culture flasks.
Cardiac progenitor cell therapy: mechanisms of action
Authors: Bryl Rut , Kulus Magdalena , Bryja Artur , Domagała Dominika , Mozdziak Paul , Antosik Paweł , Bukowska Dorota , Zabel Maciej , Dzięgiel Piotr , Kempisty Bartosz
Published: March 2024

Heart failure (HF) is an end-stage of many cardiac diseases and one of the main causes of death worldwide. The current management of this disease remains suboptimal. The adult mammalian heart was considered a post-mitotic organ. However, several reports suggest that it may possess modest regenerative potential. Adult cardiac progenitor cells (CPCs), the main players in the cardiac regeneration, constitute, as it may seem, a heterogenous group of cells, which remain quiescent in physiological conditions and become activated after an injury, contributing to cardiomyocytes renewal. They can mediate their beneficial effects through direct differentiation into cardiac cells and activation of resident stem cells but majorly do so through paracrine release of factors. CPCs can secrete cytokines, chemokines, and growth factors as well as exosomes, rich in proteins, lipids and non-coding RNAs, such as miRNAs and YRNAs, which contribute to reparation of myocardium by promoting angiogenesis, cardioprotection, cardiomyogenesis, anti-fibrotic activity, and by immune modulation. Preclinical studies assessing cardiac progenitor cells and cardiac progenitor cells-derived exosomes on damaged myocardium show that administration of cardiac progenitor cells-derived exosomes can mimic effects of cell transplantation. Exosomes may become new promising therapeutic strategy for heart regeneration nevertheless there are still several limitations as to their use in the clinic. Key questions regarding their dosage, safety, specificity, pharmacokinetics, pharmacodynamics and route of administration remain outstanding. There are still gaps in the knowledge on basic biology of exosomes and filling them will bring as closer to translation into clinic.
The neuroscience of human empathy for pleasure: protocol for a scoping review
Authors: Mello Manuel , Fusaro Martina , Aglioti Salvatore Maria
Published: March 2024

Objective

The neuroscience of human empathy for pleasure and positive affect is an emergent, scarcely addressed topic. The main aim of this scoping review is to map the impact of this new research domain on the field of social and affective neuroscience.

Introduction

Most of the literature on empathy and affect sharing has hitherto focused on negative emotions, with a special focus on pain. However, understanding, sharing, and reacting to others’ pleasures is an evolutionarily and socially important function. Our scoping review addresses this gap in the literature and tries to unify the available information under the empathy for pleasure umbrella.

Inclusion criteria

This scoping review is intended to cover studies on empathy for positive emotions, pleasant sensory outcomes, and other rewards in healthy individuals and neurological/neuropsychiatric/neurodevelopmental disorders populations.

Methods

We will perform a systematic search in the Medline (PubMed), Scopus, and Web of Science (WoS) databases. Two authors will independently screen all titles, abstracts, and then full-text articles that meet the inclusion criteria. The year range of interest will be 2000–2022, and only journal articles published in English will be assessed. Data will be extracted and presented in tables and/or graphical representations to synthesize and describe the results. The extracted data will be reported in a comprehensive summary.

Results

The final manuscript is intended for submission to an indexed journal in late 2023/beginning 2024.

Conclusions

To our knowledge, the present scoping review will be the first to address the variety and heterogeneity of available evidence on human empathy for pleasure. We ultimately aim at perusing the growing literature on this far-reaching field of study and informing future research.

Systematic review registration

The neuroscience of human empathy for pleasure: Protocol for a scoping review. https://doi.org/10.17605/OSF.IO/W7H6J. (December 27, 2022).
Nitrogen uptake in lentil cultivar mixtures is not predictable from pure stands performance but is correlated with agronomic parameters and experimental conditions
Authors: Lorenzetti Elisa , Carlesi Stefano , Michelsen Anders , Bàrberi Paolo
Published: March 2024

Background

In the context of rising costs of raw materials and environmental degradation caused by livestock farming, the agri-food sector faces significant challenges in sourcing sustainable proteins. Grain legumes have emerged as cost-effective protein sources, with lower water footprint and GHG emissions compared to animal sources. However, their cultivation is threatened by strong yield fluctuations. Leveraging intra-specific diversity through cultivar mixtures in cropping systems can effectively buffer biotic and abiotic stresses, hence increasing yield stability. In this study, we investigate the effect of intra-specific diversity on lentil nitrogen uptake under pot (2020) and field conditions (2021). We hypothesize that cultivars with higher affinity for nitrogen fixation influence the other components of the mixture, and that nitrogen uptake dynamics are a possible driver in modulating cultivar mixture behaviour. We designed two-, three-, and four-cultivar mixtures with a trait-blind approach and compared them to sole cultivars.

Results and conclusions

Our results show inconsistencies across the two experimental years, indicating that lentils may shift their nitrogen source from the atmosphere to the soil when grown in pots. Mixtures 15N enrichment was not always consistent with pure stand performance, suggesting that cultivar mixtures may have an unpredictable cumulative effect on nitrogen uptake. Regarding correlations with agronomic parameters, we observed a significant correlation between nodules number and nitrogen concentration, regardless of experimental conditions. Finally, we found that 15N excess emerged as a significant predictor for pure stands’ yield, but the differences were diluted with the increase in diversity levels. The findings on 15N enrichment responses, cultivar impacts, and complex mixture effects on soil microbiota underscore the need for further research.
Examining user behavior with machine learning for effective mobile peer-to-peer payment adoption
Authors: Antonio Blanco-Oliver , Juan Lara-Rubio , Ana Irimia-Diéguez , Francisco Liébana-Cabanillas
Published: March 2024

Disruptive innovations caused by FinTech (i.e., technology-assisted customized financial services) have brought digital peer-to-peer (P2P) payments to the fore. In this challenging environment and based on theories about customer behavior in response to technological innovations, this paper identifies the drivers of consumer adoption of mobile P2P payments and develops a machine learning model to predict the use of this thriving payment option. To do so, we use a unique data set with information from 701 participants (observations) who completed a questionnaire about the adoption of Bizum, a leading mobile P2P platform worldwide. The respondent profile was the average Spanish citizen within the framework of European culture and lifestyle. We document (in this order of priority) the usefulness of mobile P2P payments, influence of peers and other social groups such as friends, family, and colleagues on individual behavior (that is, subjective norms), perceived trust, and enjoyment of the user experience within the digital context and how those attributes better classify (potential) users of mobile P2P payments. We also find that nonparametric approaches based on machine learning algorithms outperform traditional parametric methods. Finally, our results show that feature selection based on random forest, such as the Boruta procedure, as a preprocessing technique substantially increases prediction performance while reducing noise, redundancy of the resulting model, and computational costs. The main limitation of this research is that it only has a place within the sociocultural and institutional framework of the Spanish population. It is therefore desirable to replicate this study by surveying people from other countries to analyze the effects of the institutional environment on the adoption of mobile P2P payments.