bluuebunny/crossref_metadata_2025 huggingface dataset:
Unilateral acute posterior multifocal placoid pigment epitheliopathy (APMPPE) with delayed contralateral eye involvement
Authors: Mordechaev Emanuel , Shakarov Gabriel , Parikh Deep
Published: January 2024

Background

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a rare presumed inflammatory chorioretinopathy characterized by creamy, yellow-white placoid lesions at the level of the retinal pigment epithelium (RPE). Unilateral cases often have fellow eye involvement within days to a few weeks. This report details a rare case of delayed contralateral APMPPE, in which unilateral lesion resolution was followed by contralateral eye involvement 31 months later.

Case presentation

A 38-year-old woman presented with three days of blurry vision and photopsias in the right eye (OD). She endorsed a viral GI illness one month prior. Visual acuity was 20/25 -2 OD and 20/20 -1 in the left eye (OS). Examination revealed creamy, yellow-white placoid lesions in the posterior pole. Fluorescein angiography (FA) was notable for early hypofluorescence and late hyperfluorescence of the lesions, consistent with APMPPE. MRI and MRA brain were negative for cerebral vasculitis. She was treated with oral prednisone with complete resolution of her symptoms, vision, and lesion regression. She then presented 31 months later, with blurry vision OS and similar new creamy, yellow-white placoid lesions in the posterior pole OS. She endorsed receiving an influenza vaccine one month prior. FA again was notable for early hypofluorescence. She was diagnosed with APMPPE, this time involving the left eye, and was once again started on oral steroids with complete resolution. She denied any neurologic symptoms.

Conclusions

APMPPE is an inflammatory vasculitis of the choroid, leading to hypoperfusion and ischemic injury of the RPE with subsequent lesion formation. APMPPE may be preceded by a viral prodrome or vaccination, both of which were seen in this case. Choroidal inflammation seen in APMPPE is therefore thought to stem from immune-mediated processes. Unilateral cases often have fellow eye involvement within days to a few weeks. Single eye involvement with delayed contralateral presentation, as seen in our patient, is rare. This case demonstrates that lesion resolution in one eye can be followed by contralateral eye involvement up to 31 months later, highlighting the importance of routine ophthalmic monitoring for patients with unilateral APMPPE.
Women empowerment and childhood stunting: evidence from rural northwest Ethiopia
Authors: Wassie Emebet Gashaw , Tenagashaw Mesfin Wogayehu , Tiruye Tenaw Yimer
Published: January 2024

Background

Women are often the primary caregivers of children, and as such, their empowerment could influence the nutritional status of their children. However, the role of maternal empowerment on the nutritional status of children in Ethiopia is largely unknown.

Aim

To determine the association of women’s empowerment with childhood stunting in rural northwest Ethiopia.

Methods

A community-based cross-sectional study was conducted among 582 mothers with children aged 6–59 months. A multistage sampling technique was used to select the study participants. Binomial logistic regression analyses were used to assess whether women’s empowerment (categorized as low, moderate and high) and its five dimensions (household decision-making, educational status, cash earnings, house/land ownership, and membership in community groups) were associated with stunting in children. Odds ratios with 95% CI were estimated, and statistical significance was declared at a p-value of < 0.05.

Results

A total of 114 (19.6%), 312 (53.6%), and 156 (26.8%) participants had low, moderate, and high empowerment levels, respectively. In addition, 255 (43.8%) mothers had children who were stunted (too short for their age). In the adjusted models, mothers with moderate empowerment (AOR 0.60, 95% CI: 0.35, 0.97) and high empowerment (AOR 0.56, 95% CI: 0.37, 0.86) had lower odds of having stunted children compared to mothers with low empowerment. Mothers who had a secondary education or higher (AOR 0.57, 95% CI: 0.35, 0.93), owned a house or land (AOR 0.64, 95% CI: 0.44, 0.94) and were members of community groups (AOR 0.54, 95% CI: 0.36, 0.80) were less likely to have stunted children.

Conclusion

High women empowerment was significantly associated with a lower likelihood of childhood stunting. The findings suggest a need to look beyond the direct causes of stunting and incorporate targeted strategies for empowering women into child nutrition programs.
Factor structure of psychosis screening questionnaire in Ugandan adults
Authors: Kwagala Claire , Ametaj Amantia , Kim Hannah H. , Kyebuzibwa Joseph , Okura Rogers , Stevenson Anne , Gelaye Bizu , Akena Dickens
Published: January 2024

Background

Psychotic disorders are common and contribute significantly to morbidity and mortality of people with psychiatric diseases. Therefore, early screening and detection may facilitate early intervention and reduce adverse outcomes. Screening tools that lay persons can administer are particularly beneficial in low resource settings. However, there is limited research evaluating the validity of psychosis screening instruments in Uganda. We aimed to assess the construct validity and psychometric properties of the Psychosis Screening Questionnaire (PSQ) in Uganda in a population with no history of a psychotic disorder.

Methods

The sample consisted of 2101 Ugandan adults participating as controls in a larger multi-country case-control study on psychiatric genetics who were recruited between February 2018 and March 2020. Participants were individuals seeking outpatient general medical care, caretakers of individuals seeking care, and staff or students recruited from five medical facilities that were age 18 years or older and able to provide consent. Individuals were excluded who had acute levels of alcohol or substance use, including being under inpatient hospitalization or acute medical care for one of these conditions. We used confirmatory factor analysis (CFA) and item response theory (IRT) to evaluate the factor structure and item properties of the PSQ.

Results

The overall prevalence screening positive for psychotic symptoms was 13.9% 95% CI (12.4,15.4). “Strange experiences” were the most endorsed symptoms 6.6% 95% CI (5.6,7.8). A unidimensional model seemed to be a good model or well-fitting based on fit indices including the root mean square error of approximation (RMSEA of 0.00), comparative fit index (CFI of 1.000), and Tucker-Lewis Index (TLI of 1.000). The most discriminating items along the latent construct of psychosis were items assessing thought disturbance followed by items assessing paranoia, with a parameter (discrimination) value of 2.53 and 2.40, respectively.

Conclusion

The PSQ works well in Uganda as an initial screening tool for moderate to high-level of psychotic symptoms.
Effect of low-frequency noise exposure on cognitive function: a systematic review and meta-analysis
Authors: Liang Peng , Li Jiangjing , Li Zenglei , Wei Jing , Li Jing , Zhang Shenghao , Xu Shenglong , Liu Zhaohui , Wang Jin
Published: January 2024

Background

Low-frequency noise may cause changes in cognitive function. However, there is no established consensus on the effect of low-frequency noise on cognitive function. Therefore, this systematic review and meta-analysis aimed to explore the relationship between low-frequency noise exposure and cognitive function.

Methods

We conducted a systematic review and identified original studies written in English on low-frequency noise and cognition published before December 2022 using the PsycINFO, PubMed, Medline, and Web of Science databases. The risk of bias was evaluated according to established guidelines. A random-effects meta-analysis was performed where appropriate. To explore the association between low-frequency noise exposure and cognitive function, we reviewed eight relevant studies. These studies covered cognitive functions grouped into four domains: attention, executive function, memory, and higher-order cognitive functions. The data extraction process was followed by a random-effects meta-analysis for each domain, which allowed us to quantify the overall effect.

Results

Our analysis of the selected studies suggested that interventions involving low-frequency noise only had a negative impact on higher-order cognitive functions (Z = 2.42,p = 0.02), with a standardized mean difference of -0.37 (95% confidence interval: -0.67, -0.07). A moderate level of heterogeneity was observed among studies (p = 0.24, I2 = 29%, Tau2 = 0.03).

Conclusions

Our study findings suggest that low-frequency noise can negatively impact higher-order cognitive functions, such as logical reasoning, mathematical calculation, and data processing. Therefore, it becomes important to consider the potential negative consequences of low-frequency noise in everyday situations, and proactive measures should be taken to address this issue and mitigate the associated potential adverse outcomes.
Association of lymphocyte subsets and cytokines with bone metabolism: a retrospective, cross-sectional study
Authors: Peng Cong , Yang Qiao , Kong Xiangrui , Sun Zhengzhong , Wang Liang , Xiao Li
Published: January 2024

Background

Previous research has shown that lymphocytes and cytokines can mediate bone metabolism. This study explored the clinical association and predictive ability of lymphocytes and cytokines levels for bone metabolism.

Methods

A total of 162 patients were enrolled in this study. The levels of N-terminal propeptide of type I procollagen (P1NP), β-collagen degradation product (β-CTX), total T lymphocytes, immature T lymphocytes, suppressor/cytotoxic T lymphocytes, helper/inducer T lymphocytes, B lymphocytes, natural killer (NK) cells, Interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), IFN-α, interleukin-1 beta (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL12p70 were evaluated. The relationship between these lymphocyte subsets and cytokines with bone metabolic status was examined and their predictive ability for bone metabolic status was assessed.

Results

The principal component analysis (PCA) and correlation analysis results varied on differences in lymphocyte subsets and cytokines in various bone metabolism states. Differential analysis revealed significant differences in the absolute counts of B lymphocytes (P < 0.05), level of IL-12p70 (P < 0.05), and IL-8 (P < 0.001) at different P1NP levels. Significant differences were observed in the absolute counts of total T lymphocytes (P < 0.05), B lymphocytes (P < 0.05), the level of IL-6 (P < 0.05), the percentage of B lymphocytes (P < 0.01), and NK cells (P < 0.05) at different β-CTX levels. Furthermore, the receiver operating characteristic (ROC) curve showed that the absolute count of B lymphocytes and levels of IL-12p70 and IL-8 could be used to evaluate bone formation states, while the absolute counts of T and B lymphocytes, level of IL-6, and percentages of NK cells and B lymphocytes could be used to evaluate bone resorption states.

Conclusion

The bone metabolism status changed based on the lymphocyte subsets and cytokine levels. Differentially expressed lymphocytes and cytokines could be used to distinguish bone metabolism status.
Prediction of the active compounds and mechanism of Biochanin A in the treatment of Legg-Calvé-Perthes disease based on network pharmacology and molecular docking
Authors: Liu Jianhong , Hua Zhirui , Liao Shijie , Li Boxiang , Tang Shengping , Huang Qian , Wei Zhendi , Lu Rongbin , Lin Chengsen , Ding Xiaofei
Published: January 2024

Background

Legg-Calvé-Perthes disease is a special self-limited disease in pediatric orthopedics with a high disability rate and a long-term course, and there is still no clear and effective therapeutic drug in clinic. This study aimed to investigate the potential efficacy of biochanin A, a kind of oxygen-methylated isoflavone compound, in treating Perthes disease based on network pharmacology, molecular docking and in vitro experiments.

Methods

IL-6 was used to stimulate human umbilical vein endothelial cells to construct endothelial cell dysfunction model. We demonstrated whether biochanin A could alleviate endothelial dysfunction through CCK8 assay, immunofluorescence. Targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. Targets of endothelial dysfunction were obtained from Genecards and OMIM databases. Protein–protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomics analyses were used to analyze the potential target and the key pathway of the anti-endothelial dysfunction activity of biochanin A. To validate the potential target-drug interactions, molecular docking and molecular dynamics simulations were performed and the result was proved by western blot.

Results

It was found that biochanin A can promote the expression of ZO-1, reduce the expression of ICAM-1, which means improving endothelial dysfunction. A total of 585 targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. A total of 10,832 targets of endothelial dysfunction were obtained from Genecards and OMIM databases. A total of 527 overlapping targets of endothelial dysfunction and biochanin A were obtained. AKT1, TNF-α, VCAM1, ICAM1, and NOS3 might be the key targets of the anti-endothelial dysfunction activity of biochanin A, and the key pathways might be PI3K-Akt and TNF signaling pathways. Molecular docking results indicated that the AKT1 and TNF-α had the highest affinity binding with biochanin A.

Conclusion

This study indicates that biochanin A can target AKT1 and TNF-α to alleviate endothelial dysfunction induced by IL-6 in Perthes disease, which provides a theoretical basis for the treatment of Perthes disease by using biochanin A.
Parental satisfaction with paediatric care with and without the support of an eHealth device: a quasi-experimental study in Sweden
Authors: Foldager Jeppesen Sarah , Vilhjálmsson Rúnar , Åvik Persson Helene , Kristensson Hallström Inger
Published: January 2024

Background

The period after a child is discharged from hospital is generally described as challenging for the parents. Their satisfaction with the health services received is an important indicator of the quality of care. eHealth devices are increasingly used in health care to support communication with parents. Differences in levels of parental satisfaction by modality of provided care or by parental background are largely unknown. This study aimed to describe satisfaction with health care between sociodemographic groups of parents, who either received or did not receive an eHealth device for communication between parents and hospital staff as a supplement to routine care after a child’s discharge from neonatal or paediatric surgery departments.

Methods

Data from a quasi-experimental study was collected in the south of Sweden, between 2019 and 2021. The Pediatric Quality of Life Inventory™ (PedsQL) Healthcare Satisfaction Generic Module was used to assess the parents’ satisfaction with different dimensions of health care. Seventy parents of children hospitalized in a neonatal or a paediatric surgery department were enrolled in intervention (eHealth device, n = 36) and control (no eHealth device, n = 34) groups.

Results

The parents reported high overall satisfaction with the health care provided and were also highly satisfied within different dimensions of care. Moreover, they reported high satisfaction with using an eHealth device, although having support from the eHealth device was related to neither higher nor lower levels of satisfaction with care. There was a significant difference between fathers and mothers in the multivariate sub-analysis in certain instances regarding satisfaction with communication and the level of inclusion.

Conclusions

Parents were very satisfied with the health care provided, whether or not they received eHealth. Further research looking at groups with and without the support of an eHealth device is required to further develop future paediatric and neonatal care interventions. Communication and support through eHealth can be a tool to alleviate the distress parents experience after their child’s hospital admission, accommodate the family’s transfer to home, and increase satisfaction with care, but it needs to be evaluated before being implemented.

Trial registration

Clinical Trials NCT04150120, first registration 4/11/2019.
LASS2 enhances chemosensitivity to cisplatin by inhibiting PP2A-mediated β-catenin dephosphorylation in a subset of stem-like bladder cancer cells
Authors: Shi Hongjin , Tan Zhiyong , Duan Bowen , Guo Chunming , Li Chong , Luan Ting , Li Ning , Huang Yinglong , Chen Shi , Gao Jixian , Feng Wei , Xu Haole , Wang Jiansong , Fu Shi , Wang Haifeng
Published: January 2024

Background

The benefits of first-line, cisplatin-based chemotherapy for muscle-invasive bladder cancer are limited due to intrinsic or acquired resistance to cisplatin. Increasing evidence has revealed the implication of cancer stem cells in the development of chemoresistance. However, the underlying molecular mechanisms remain to be elucidated. This study investigates the role of LASS2, a ceramide synthase, in regulating Wnt/β-catenin signaling in a subset of stem-like bladder cancer cells and explores strategies to sensitize bladder cancer to cisplatin treatment.

Methods

Data from cohorts of our center and published datasets were used to evaluate the clinical characteristics of LASS2. Flow cytometry was used to sort and analyze bladder cancer stem cells (BCSCs). Tumor sphere formation, soft agar colony formation assay, EdU assay, apoptosis analysis, cell viability, and cisplatin sensitivity assay were used to investigate the functional roles of LASS2. Immunofluorescence, immunoblotting, coimmunoprecipitation, LC–MS, PCR array, luciferase reporter assays, pathway reporter array, chromatin immunoprecipitation, gain-of-function, and loss-of-function approaches were used to investigate the underlying mechanisms. Cell- and patient-derived xenograft models were used to investigate the effect of LASS2 overexpression and a combination of XAV939 on cisplatin sensitization and tumor growth.

Results

Patients with low expression of LASS2 have a poorer response to cisplatin-based chemotherapy. Loss of LASS2 confers a stem-like phenotype and contributes to cisplatin resistance. Overexpression of LASS2 results in inhibition of self-renewal ability of BCSCs and increased their sensitivity to cisplatin. Mechanistically, LASS2 inhibits PP2A activity and dissociates PP2A from β-catenin, preventing the dephosphorylation of β-catenin and leading to the accumulation of cytosolic phospho-β-catenin, which decreases the transcription of the downstream genes ABCC2 and CD44 in BCSCs. Overexpression of LASS2 combined with a tankyrase inhibitor (XAV939) synergistically inhibits tumor growth and restores cisplatin sensitivity.

Conclusions

Targeting the LASS2 and β-catenin pathways may be an effective strategy to overcome cisplatin resistance and inhibit tumor growth in bladder cancer patients.
Evolution of cell therapy for renal cell carcinoma
Authors: Wang Yufei , Suarez Eloah Rabello , Kastrunes Gabriella , de Campos Najla Santos Pacheco , Abbas Rabia , Pivetta Renata Schmieder , Murugan Nithyassree , Chalbatani Ghanbar Mahmoodi , D’Andrea Vincent , Marasco Wayne A.
Published: January 2024

Treatment for renal cell carcinoma (RCC) has improved dramatically over the last decade, shifting from high-dose cytokine therapy in combination with surgical resection of tumors to targeted therapy, immunotherapy, and combination therapies. However, curative treatment, particularly for advanced-stage disease, remains rare. Cell therapy as a “living drug” has achieved hematological malignancy cures with a high response rate, and significant research efforts have been made to facilitate its translation to solid tumors. Herein, we overview the cellular therapies for RCC focusing on allogeneic hematopoietic stem cell transplantation, T cell receptor gene-modified T cells, chimeric antigen receptor (CAR) T cells, CAR natural killer (NK) cells, lymphokine-activated killer (LAK) cells, γδ T cells, and dendritic cell vaccination. We have also included perspectives for using other recent approaches, such as CAR macrophages, dendritic cell-cytokine induced killer cells and regulatory CAR-T cells to shed light on preclinical development of cell therapy and advancing cell therapy into clinic to achieve cures for RCC.
Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy
Authors: Chehelgerdi Mohammad , Chehelgerdi Matin , Khorramian-Ghahfarokhi Milad , Shafieizadeh Marjan , Mahmoudi Esmaeil , Eskandari Fatemeh , Rashidi Mohsen , Arshi Asghar , Mokhtari-Farsani Abbas
Published: January 2024

The CRISPR system is a revolutionary genome editing tool that has the potential to revolutionize the field of cancer research and therapy. The ability to precisely target and edit specific genetic mutations that drive the growth and spread of tumors has opened up new possibilities for the development of more effective and personalized cancer treatments. In this review, we will discuss the different CRISPR-based strategies that have been proposed for cancer therapy, including inactivating genes that drive tumor growth, enhancing the immune response to cancer cells, repairing genetic mutations that cause cancer, and delivering cancer-killing molecules directly to tumor cells. We will also summarize the current state of preclinical studies and clinical trials of CRISPR-based cancer therapy, highlighting the most promising results and the challenges that still need to be overcome. Safety and delivery are also important challenges for CRISPR-based cancer therapy to become a viable clinical option. We will discuss the challenges and limitations that need to be overcome, such as off-target effects, safety, and delivery to the tumor site. Finally, we will provide an overview of the current challenges and opportunities in the field of CRISPR-based cancer therapy and discuss future directions for research and development. The CRISPR system has the potential to change the landscape of cancer research, and this review aims to provide an overview of the current state of the field and the challenges that need to be overcome to realize this potential.
Transcriptomic signatures of individual cell types in cerebral cavernous malformation
Authors: Li Ying , Girard Romuald , Srinath Abhinav , Cruz Diana Vera , Ciszewski Cezary , Chen Chang , Lightle Rhonda , Romanos Sharbel , Sone Je Yeong , Moore Thomas , DeBiasse Dorothy , Stadnik Agnieszka , Lee Justine J. , Shenkar Robert , Koskimäki Janne , Lopez-Ramirez Miguel A. , Marchuk Douglas A. , Ginsberg Mark H. , Kahn Mark L. , Shi Changbin , Awad Issam A.
Published: January 2024

Cerebral cavernous malformation (CCM) is a hemorrhagic neurovascular disease with no currently available therapeutics. Prior evidence suggests that different cell types may play a role in CCM pathogenesis. The contribution of each cell type to the dysfunctional cellular crosstalk remains unclear. Herein, RNA-seq was performed on fluorescence-activated cell sorted endothelial cells (ECs), pericytes, and neuroglia from CCM lesions and non-lesional brain tissue controls. Differentially Expressed Gene (DEG), pathway and Ligand-Receptor (LR) analyses were performed to characterize the dysfunctional genes of respective cell types within CCMs. Common DEGs among all three cell types were related to inflammation and endothelial-to-mesenchymal transition (EndMT). DEG and pathway analyses supported a role of lesional ECs in dysregulated angiogenesis and increased permeability. VEGFA was particularly upregulated in pericytes. Further pathway and LR analyses identified vascular endothelial growth factor A/ vascular endothelial growth factor receptor 2 signaling in lesional ECs and pericytes that would result in increased angiogenesis. Moreover, lesional pericytes and neuroglia predominantly showed DEGs and pathways mediating the immune response. Further analyses of cell specific gene alterations in CCM endorsed potential contribution to EndMT, coagulation, and a hypoxic microenvironment. Taken together, these findings motivate mechanistic hypotheses regarding non-endothelial contributions to lesion pathobiology and may lead to novel therapeutic targets.
Role of cell rearrangement and related signaling pathways in the dynamic process of tip cell selection
Authors: Guo Yaru , Zhang Shihan , Wang Dandan , Heng Boon Chin , Deng Xuliang
Published: January 2024

Angiogenesis is a complex, highly-coordinated and multi-step process of new blood vessel formation from pre-existing blood vessels. When initiated, the sprouting process is spearheaded by the specialized endothelial cells (ECs) known as tip cells, which guide the organization of accompanying stalk cells and determine the function and morphology of the finally-formed blood vessels. Recent studies indicate that the orchestration and coordination of angiogenesis involve dynamic tip cell selection, which is the competitive selection of cells to lead the angiogenic sprouts. Therefore, this review attempt to summarize the underlying mechanisms involved in tip cell specification in a dynamic manner to enable readers to gain a systemic and overall understanding of tip cell formation, involving cooperative interaction of cell rearrangement with Notch and YAP/TAZ signaling. Various mechanical and chemical signaling cues are integrated to ensure the right number of cells at the right place during angiogenesis, thereby precisely orchestrating morphogenic functions that ensure correct patterning of blood vessels.
DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells
Authors: Kwon ChangHyuk , Cho Wonjun , Choi Sung Woo , Oh Heeseung , Abd El-Aty A. M. , Gecili Ibrahim , Jeong Ji Hoon , Jung Tae Woo
Published: January 2024

Background

Age-related macular degeneration (AMD) is an irreversible eye disease that can cause blurred vision. Regular exercise has been suggested as a therapeutic strategy for treating AMD, but how exercise improves AMD is not yet understood. This study investigated the protective effects of developmental endothelial locus-1 (DEL-1), a myokine upregulated during exercise, on endoplasmic reticulum (ER) stress-induced injury in retinal pigment epithelial cells.

Methods

We evaluated the levels of AMPK phosphorylation, autophagy markers, and ER stress markers in DEL-1-treated human retinal pigment epithelial cells (hRPE) using Western blotting. We also performed cell viability, caspase 3 activity assays, and autophagosome staining.

Results

Our findings showed that treatment with recombinant DEL-1 dose-dependently reduced the impairment of cell viability and caspase 3 activity in tunicamycin-treated hRPE cells. DEL-1 treatment also alleviated tunicamycin-induced ER stress markers and VEGF expression. Moreover, AMPK phosphorylation and autophagy markers were increased in hRPE cells in the presence of DEL-1. However, the effects of DEL-1 on ER stress, VEGF expression, and apoptosis in tunicamycin-treated hRPE cells were reduced by AMPK siRNA or 3-methyladenine (3-MA), an autophagy inhibitor.

Conclusions

Our study suggests that DEL-1, a myokine, may have potential as a treatment strategy for AMD by attenuating ER stress-induced injury in retinal pigment epithelial cells.
Circ_0006640 transferred by bone marrow-mesenchymal stem cell-exosomes suppresses lipopolysaccharide-induced apoptotic, inflammatory and oxidative injury in spinal cord injury
Authors: Yang Dan , Wei Haitang , Sheng Yang , Peng Tao , Zhao Qiang , Xie Liang , Yang Jun
Published: January 2024

Background

Emerging proofs have shown that differentially expressed circular RNAs (circRNAs) are closely associated with the pathophysiological process of spinal cord injury (SCI). Mesenchymal stem cell (MSC)-exosomes have been demonstrated to possess favorable therapeutic effects in diseases. Herein, this work aimed to investigate the action of circ_0006640 transferred by MSC-exosomes functional recovery after SCI.

Methods

SCI animal models were established by spinal cord contusion surgery in mice and lipopolysaccharide (LPS)-stimulated mouse microglial cell line BV2. Levels of genes and proteins were detected by qRT-PCR and Western blot. Properties of BV2 cells were characterized using CCK-8 assay, flow cytometry and ELISA analysis. The oxidative stress was evaluated. Dual-luciferase reporter assay was used for verifying the binding between miR-382-5p and circ_0006640 or IGF-1 (Insulin-like Growth Factor 1). Exosome separation was conducted by using the commercial kit.

Results

Circ_0006640 expression was lower in SCI mice and LPS-induced microglial cells. Circ_0006640 overexpression protected microglial cells from LPS-induced apoptotic, inflammatory and oxidative injury. Mechanistically, circ_0006640 directly sponged miR-382-5p, which targeted IGF-1. MiR-382-5p was increased, while IGF-1 was decreased in SCI mice and LPS-induced microglial cells. Knockdown of miR-382-5p suppressed apoptosis, inflammation and oxidative stress in LPS-induced microglial cells, which were reversed by IGF-1 deficiency. Moreover, miR-382-5p up-regulation abolished the protective functions of circ_0006640 in LPS-induced microglial cells. Additionally, circ_0006640 was packaged into MSC-exosomes and could be transferred by exosomes. Exosomal circ_0006640 also had protective effects on microglial cells via miR-382-5p/IGF-1 axis.

Conclusion

Circ_0006640 transferred by BMSC-exosomes suppressed LPS-induced apoptotic, inflammatory and oxidative injury via miR-382-5p/IGF-1 axis, indicating a new insight into the clinical application of exosomal circRNA-based therapeutic in the function recovery after SCI.
Male with an apparently normal phenotype carrying a BRCA1 exon 20 duplication in trans to a BRCA1 frameshift variant
Authors: Block Ines , Mateu-Regué Àngels , Do Thi Tuyet Nhu , Miceikaite Ieva , Sdogati Daniel , Larsen Martin J. , Hao Qin , Nielsen Henriette Roed , Boonen Susanne E. , Skytte Anne-Bine , Jensen Uffe Birk , Høffding Louise K. , De Nicolo Arcangela , Viel Alessandra , Tudini Emma , Parsons Michael T. , Hansen Thomas V. O. , Rossing Maria , Kruse Torben A. , Spurdle Amanda B. , Thomassen Mads
Published: January 2024

Background

Reports of dual carriers of pathogenic BRCA1 variants in trans are extremely rare, and so far, most individuals have been associated with a Fanconi Anemia-like phenotype.

Methods

We identified two families with a BRCA1 in-frame exon 20 duplication (Ex20dup). In one male individual, the variant was in trans with the BRCA1 frameshift variant c.2475delC p.(Asp825Glufs*21). We performed splicing analysis and used a transcription activation domain (TAD) assay to assess the functional impact of Ex20dup. We collected pedigrees and mapped the breakpoints of the duplication by long- and short-read genome sequencing. In addition, we performed a mitomycin C (MMC) assay from the dual carrier using cultured lymphoblastoid cells.

Results

Genome sequencing and RNA analysis revealed the BRCA1 exon 20 duplication to be in tandem. The duplication was expressed without skipping any one of the two exon 20 copies, resulting in a lack of wild-type transcripts from this allele. TAD assay indicated that the Ex20dup variant has a functional level similar to the well-known moderate penetrant pathogenic BRCA1 variant c.5096G > A p.(Arg1699Gln). MMC assay of the dual carrier indicated a slightly impaired chromosomal repair ability.

Conclusions

This is the first reported case where two BRCA1 variants with demonstrated functional impact are identified in trans in a male patient with an apparently normal clinical phenotype and no BRCA1-associated cancer. The results pinpoint a minimum necessary BRCA1 protein activity to avoid a Fanconi Anemia-like phenotype in compound heterozygous status and yet still predispose carriers to hormone-related cancers. These findings urge caution when counseling families regarding potential Fanconi Anemia risk. Furthermore, prudence should be taken when classifying individual variants as benign based on co-occurrence in trans with well-established pathogenic variants.
Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial)
Authors: Zapata-Arriaza Elena , Medina-Rodríguez Manuel , Moniche Álvarez Francisco , de Albóniga-Chindurza Asier , Aguilar-Pérez Marta , Ainz-Gómez Leire , Baena-Palomino Pablo , Zamora Aynara , Pardo-Galiana Blanca , Delgado-Acosta Fernando , Valverde Moyano Roberto , Jiménez-Gómez Elvira , Bravo Rey Isabel , Oteros Fernández Rafael , Escudero-Martínez Irene , Vielba-Gomez Isabel , Morales Caba Lluis , Díaz Pérez Jose , García Molina Estefania , Mosteiro Sonia , Castellanos Rodrigo María del Mar , Amaya Pascasio Laura , Hidalgo Carlos , Freijo Guerrero María del Mar , González Díaz Eva , Ramírez Moreno Jose María , Fernández Prudencio Luis , Terceño Izaga Mikel , Bashir Viturro Saima , Gamero-García Miguel Ángel , Jiménez Jorge Silvia , Rosso Fernández Clara , Montaner Joan , González García Alejandro
Published: January 2024

Rationale

In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated.

Aims

To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL.

Sample size estimates

Two hundred forty patients will be enrolled, 120 in every treatment arm.

Methods and design

A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months.

Study outcomes

Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage.

Discussion

This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL.

Trial registration

The trial is registered as NCT05225961. February, 7th, 2022.
miR-129-5p as a biomarker for pathology and cognitive decline in Alzheimer’s disease
Authors: Han Sang-Won , Pyun Jung-Min , Bice Paula J. , Bennett David A. , Saykin Andrew J. , Kim Sang Yun , Park Young Ho , Nho Kwangsik
Published: January 2024

Background

Alzheimer’s dementia (AD) pathogenesis involves complex mechanisms, including microRNA (miRNA) dysregulation. Integrative network and machine learning analysis of miRNA can provide insights into AD pathology and prognostic/diagnostic biomarkers.

Methods

We performed co-expression network analysis to identify network modules associated with AD, its neuropathology markers, and cognition using brain tissue miRNA profiles from the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) (N= 702) as a discovery dataset. We performed association analysis of hub miRNAs with AD, its neuropathology markers, and cognition. After selecting target genes of the hub miRNAs, we performed association analysis of the hub miRNAs with their target genes and then performed pathway-based enrichment analysis. For replication, we performed a consensus miRNA co-expression network analysis using the ROS/MAP dataset and an independent dataset (N= 16) from the Gene Expression Omnibus (GEO). Furthermore, we performed a machine learning approach to assess the performance of hub miRNAs for AD classification.

Results

Network analysis identified a glucose metabolism pathway-enriched module (M3) as significantly associated with AD and cognition. Five hub miRNAs (miR-129-5p, miR-433, miR-1260, miR-200a, and miR-221) of M3 had significant associations with AD clinical and/or pathologic traits, with miR129-5p by far the strongest across all phenotypes. Gene-set enrichment analysis of target genes associated with their corresponding hub miRNAs identified significantly enriched biological pathways including ErbB, AMPK, MAPK, and mTOR signaling pathways. Consensus network analysis identified two AD-associated consensus network modules and two hub miRNAs (miR-129-5p and miR-221). Machine learning analysis showed that the AD classification performance (area under the curve (AUC) = 0.807) of age, sex, andAPOEε4 carrier status was significantly improved by 6.3% with inclusion of five AD-associated hub miRNAs.

Conclusions

Integrative network and machine learning analysis identified miRNA signatures, especially miR-129-5p, as associated with AD, its neuropathology markers, and cognition, enhancing our understanding of AD pathogenesis and leading to better performance of AD classification as potential diagnostic/prognostic biomarkers.
Average effective subcarrier-domain sparse representation approach for target information estimation in CP-OFDM-based passive bistatic radar
Authors: Zhao Zhixin , Gong Yanghang , Zhou Huilin , Cao Yulong
Published: January 2024

Although some existing sparse representation (SR) methods are robust for target detection in passive bistatic radar (PBR), they still face the challenges of high computational complexity and poor detection performance for extremely low-signal-to-clutter ratio (SCR) target. So, an average effective subcarrier (AES)-domain sparse representation approach is investigated in this paper. Firstly, the AES-based SR model is proposed to solve the problem of high computational complexity, which is established by utilizing the sparseness of the orthogonal frequency-division multiplexing (OFDM) with cyclic prefix (CP) signals in each effective subcarrier domain. Then, considering the difficulty of detecting extremely low-SCR targets, clutter cancellation is implemented by the SR-based optimization model. Two AES-S algorithms, namely AES-S-based clutter cancellation in the time domain (AES-S-T) and AES-S-based clutter cancellation in the subcarrier domain (AES-S-C), are proposed, and the computational complexity is further reduced. Finally, extensive simulation and experimental results illustrate that the proposed algorithms have good detection performance and low computational complexity in PBR detection scene.
Beyond correlates: the social gradient in childhood overweight
Authors: Hermeling Lina , Steinacker Jürgen M. , Kobel Susanne
Published: January 2024

Background

Health (in)equity has a high priority on research and policy agendas. Even though it is known that inequalities in overweight prevalence accumulate with age and are already existent among children below the age of six, research on this topic is scarce. In this young age group, parents play an important role in preventing overweight and associated adverse consequences. This study examines the magnitude of parental misclassification of child weight status and its correlates, focussing on the factors that determine social status and equity.

Methods

Preschool children’s weight and height was measured objectively. Parents gave information on their socioeconomic background. Family education was dichotomised into tertiary and non-tertiary educational level, according to CASMIN. Binary logistic regression, adjusted for parental BMI, was applied to detect odds of childhood overweight.

Results

Data on family educational level and anthropometrics were available from 643 children (4.5 ± 0.82 years, 52.7% male) and their parents of which 46.5% (n = 299) had a tertiary educational background. The groups (tertiary vs. non-tertiary educational level) differ significantly in overweight prevalence (3.7% vs. 11.9%, p ≤ 0.001). Odds of overweight were two times higher in children with non-tertiary educational background (OR: 2.123, CI: 1.010–4.461, p < 0.05), adjusted for parental BMI.

Conclusion

Children from families with low educational background have an elevated risk of overweight, already at a very young age. Education in general (not explicitly health education) seems to play a tremendous role in the prevention of overweight and obesity and should therefore be implied in policies enhancing health equity.

Trial registration

DRKS-ID: DRKS00010089.
Passivation remediation of weakly alkaline Cd-contaminated soils using combined treatments of biochar and sepiolite
Authors: Zhang Yuxin , Gao Shan , Jia Hongtao , Sun Tao , Zheng Shunan , Wu Shihang , Sun Yuebing
Published: January 2024

Background

Cadmium (Cd) pollution in agricultural soils has become a priority environmental concern globally. A reasonable application of passivators is critical to address the problem. In this study, we examined the remediation effects of rice husk biochar (rBC) and sepiolite (Sep) as single and combined (rBC + Sep) treatments on Cd pollution in a weakly alkaline soil using three maize cultivars (Liyu 16, Zhengdan 958, and Sanbei 218) as test crops. We also explained the mechanisms involved in the remediation effects.

Results

The pseudo-second-order kinetic equation and Langmuir model could well describe the adsorption process of rBC + Sep for Cd2+. Compared with the control treatment (CK), soil available Cd concentration decreased by 29.51–36.34% under rBC + Sep treatment (p< 0.05) and the Cd concentrations in maize grains of Liyu 16, Zhengdan 958, and Sanbei 218 decreased by 38.08–47.85%, 37.25–45.61%, and 33.96–46.15%, respectively (p< 0.05). Following passivation treatment, soil available Cd concentration decreased and gradually changed from the exchangeable and carbonate binding forms to the Fe/Mn oxide and residual forms. The bioconcentration factors of Liyu 16 (0.05–0.09) and Sanbei 218 (0.05–0.09) were lower than those of Zhengdan 958 (0.07–0.13). In addition, rBC +Sep treatment increased soil pH and soil electrical conductivity, but the differences were not significant (p> 0.05).

Conclusions

The application of 0.2% rBC + 0.5% Sep composite passivation material to weakly alkaline Cd-contaminated soil can effectively reduce the Cd concentration of soil and maize.
Food insecurity among female farmers in rural West Sleman, Indonesia
Authors: Samputra Palupi Lindiasari , Antriyandarti Ernoiz
Published: January 2024

Background

Farmers, especially females, face the risk of food insecurity for their families. It would be interesting to examine the efforts made by female farmers who experience food insecurity due to the indirect impacts of COVID-19. This study aims to determine how female farmers deal with food insecurity risks in West Sleman. Data on food insecurity experiences are processed with Winstep software and the Rasch model. Ordinal logistic regression analysis calculates the probability of food insecurity for female farmers depending on their traits and the mitigation strategies they adopt.

Results

The findings of this research show that agricultural laborers (42.3%) are the most numerous type of female farmer, followed by land-owning farmers (40.4%) and land-tenants farmers (17.3%). Although more than 50% of the three types of farmers are food secure, laborers have a higher percentage of moderate-to-severe food insecurity (23%) than land owners (14%) and land tenants (11%). Factors that influence the occurrence of food insecurity are not using the home yard, which is physically accessible to grow food, having an agricultural income of less than IDR 500 thousand, and a house asset value of less than IDR 100 million.

Conclusions

Coping strategies for mitigating the risk of food insecurity start from within the family by prioritizing food spending, living frugally, growing food crops in your yard, committing full-time to farming, and avoiding dependence on government assistance. Then, optimizing and strengthening the community.
The implications of governance factors for economic and social upgrading in Ghana’s cocoa value chain
Authors: Kissi Evans Appiah , Herzig Christian
Published: January 2024

This paper identifies several governance factors that enable economic upgrading and the link between economic and social upgrading /downgrading of smallholders and Abusa sharecroppers in Ghana's cocoa value chain (GCVC). The findings are based on qualitative interviews and focus group discussions with various actors in GCVC. Our findings suggest two types of economic upgrading: process and product upgrading, achieved by smallholder producers and Abusa Sharecroppers in GCVC. While process upgrading is enabled by governance factors such as price stabilization and controlling opportunistic behavior, transparency in the sale of certified beans and premium management is key for product upgrading. Regarding the link between economic and social upgrading, we reveal that process upgrading leads to the same outcome of social upgrading and downgrading for smallholders and Abusa sharecroppers due to governance factors such as production and purchasing policies and lack of resources and capabilities. However, product upgrading links to social upgrading and downgrading for smallholders and Abusa sharecroppers respectively owing to governance factors such as controlling resources and bargaining power. We provide insights into key actors and their interests, drivers of change and effects of incentives that play crucial roles in shaping governance factors that influence economic and social upgrading of smallholders and Abusa sharecroppers in GCVC. In our conclusion, we identify how regulations, institutional support and conflicts of interest are key for enabling upgrading of developing countries’ agricultural value chains.
Development and preliminary validation of a novel eating disorder screening tool for vegetarians and vegans: the V-EDS
Authors: McLean Courtney P. , Chen Zhibin , Song Richard , Le Jessica , Fielding Joanne , Sharp Gemma
Published: January 2024

Background

Eating disorders have one of the highest mortality of all mental illnesses but are associated with low rates of screening and early intervention. In addition, there remains considerable uncertainty regarding the use of current standardised screening tools in measuring eating pathology in vegetarians and vegans. With these groups presenting as potential at-risk groups for disordered eating development, the present study aimed to develop and preliminary validate a novel eating disorder screening tool, the Vegetarian Vegan Eating Disorder Screener (V-EDS).

Methods

We utilised a mixed-methods approach, comprising four phases.

Results

A conceptual framework was developed from 25 community, clinician, and lived experience interviews and used to derive a preliminary set of 163 items (Phase 1). Phase 2 piloted the items to establish face and content validity through cognitive debriefing interviews of 18 additional community, clinician, and lived experience participants, resulting in a reduced, revised questionnaire of 53 items. Phase 3 involved scale purification using Item Response Theory in analysis of 230 vegetarians and 230 vegans resulting in a further reduced 18-item questionnaire. Phase 4 validated the screening tool in a large community sample of 245 vegetarians and 405 vegans using traditional psychometric analysis, finding the V-EDS supports a unidimensional factor structure with excellent internal consistency (α = 0.95–0.96) and convergent validity (0.87–0.88), and moderate discriminate validity (0.45–0.55).

Conclusions

This study provided strong initial support for the psychometric validity and theoretical assumptions of the novel V-EDS screening tool. The V-EDS has the potential to increase early intervention rates for vegetarians and vegans experiencing eating disorder symptoms, further supporting advocacy and treatment approaches for these expanding dietary groups.