bluuebunny/crossref_metadata_2025 huggingface dataset:
nlive: an R package to facilitate the application of the sigmoidal and random changepoint mixed models
Authors: Capuano Ana W. , Wagner Maude
Published: November 2023

Background

The use of mixed effect models with a specific functional form such as the Sigmoidal Mixed Model and the Piecewise Mixed Model (or Changepoint Mixed Model) with abrupt or smooth random change allows the interpretation of the defined parameters to understand longitudinal trajectories. Currently, there are no interface R packages that can easily fit the Sigmoidal Mixed Model allowing the inclusion of covariates or incorporating recent developments to fit the Piecewise Mixed Model with random change.

Results

To facilitate the modeling of the Sigmoidal Mixed Model, and Piecewise Mixed Model with abrupt or smooth random change, we have created an R package called nlive. All needed pieces such as functions, covariance matrices, and initials generation were programmed. The package was implemented with recent developments such as the polynomial smooth transition of the piecewise mixed model with improved properties over Bacon-Watts, and the stochastic approximation expectation-maximization (SAEM) for efficient estimation. It was designed to help interpretation of the output by providing features such as annotated output, warnings, and graphs. Functionality, including time and convergence, was tested using simulations. We provided a data example to illustrate the package use and output features and interpretation. The package implemented in the R software is available from the Comprehensive R Archive Network (CRAN) athttps://CRAN.R-project.org/package=nlive.

Conclusions

The nlive package for R fits the Sigmoidal Mixed Model and the Piecewise Mixed: abrupt and smooth. The nlive allows fitting these models with only five mandatory arguments that are intuitive enough to the less sophisticated users.
Incidence and prevalence of neurological disorders in the United Arab Emirates: a systematic review
Authors: Benamer Hani T. S. , Loney Tom
Published: November 2023

Background/Objectives

The United Arab Emirates (UAE) is a rapidly developing country. With the increase in average life-expectancy, high rates of consanguinity, and the adoption of a Western lifestyle, the burden of neurological disorders is expected to increase over the next few decades. Despite the importance of neurological disorders, there has not been a systematic review of published studies on the epidemiology of neurological disorders in the UAE.

Methods

We searched for studies of incidence and/or prevalence of neurological disorders in the UAE published in English in MEDLINE, Google Scholar, Embase, and Scopus databases with no date restrictions up until 01 October 2023. Two authors independently assessed abstracts and full texts of possibly relevant papers, followed by data extraction from studies satisfying the eligibility criteria.

Results

Eight articles (N = 2067 patients) were included, half reported incidence and prevalence of multiple sclerosis, with an average crude prevalence 56/100,000 and related demyelinating disorders. Others were related to headache, meningitis, cerebral venous thrombosis, and brain tumours.

Conclusion

There is a distinct lack of data on the epidemiology of different neurological diseases in the UAE. Large population-based studies, ideally longitudinal, are required to provide accurate and reliable estimates of the incidence and prevalence of neurological disorders to help inform healthcare capacity planning.
Clinical retrospective analysis with a predictive model for diffused-tenosynovial giant cell tumors of the temporomandibular joint
Authors: Liu Ying , Huang Yingying , Zhu Dongwang , Li Jiang , Zhao Tongchao , He Yining , Xia Ronghui , Zhong Laiping
Published: November 2023

Background

This study aimed to find out the characteristics in relation to tumor recurrence in diffused-tenosynovial giant cell tumor of temporomandibular joint and to develop and validate the prognostic model for personalized prediction.

Methods

From April 2009 to January 2021, patients with diffused-tenosynovial giant cell tumor of temporomandibular joint at a single center were included in this study. The clinical features and local recurrence-free survival were assessed through the expression of the Ki-67 index and colony-stimulating factor 1 receptor expression. Both univariate and multivariate analyses were performed on the prognostic factors for local recurrence-free survival. An independent predictor nomogram and pertinent tumor characteristics were included.

Results

The retrospective study enrolling seventy eligible patients at the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. During the follow-up time, eleven patients suffered tumor recurrence. Age was an independent risk factor for local recurrence-free survival (P = 0.032). The Ki-67 index varied significantly in different sites (P = 0.034) and tumor volume (P = 0.017). Multivariate logistic regression was used to develop the prediction model using both statistical significance and prognostic indicators. The C-index of the nomogram based on age, site, Ki-67, and colony-stimulating factor 1 receptor was 0.833. These variates provided good predicted accuracy for a nomogram on local recurrence-free survival. Diffused-tenosynovial giant cell tumor from the temporomandibular joint is extremely uncommon, and certain clinical traits are linked to the tumor proliferation index.

Conclusions

We identified the risk indicators and developed a nomogram in this study to forecast the likelihood of local recurrence-free survival in patients with diffused-tenosynovial giant cell tumor from temporomandibular joint.
Patients’ preferences for delivering bad news in palliative care in Ethiopia: a qualitative study
Authors: Ayalew Ephrem Abathun , Mphuthi Ditaba David , Matlhaba Kholofelo Lorraine
Published: November 2023

Background

One of the major challenges for healthcare professionals relates to awareness of patients’ preferences relative to how and when to break bad news and how much information should be disclosed in the eventuality of a serious medical diagnosis or prognosis. On occasions, a serious medical diagnosis or prognosis is withheld from the patient. There is a scarcity of evidence about cultural preferences regarding breaking bad news in the palliative care setting in Ethiopia. Therefore, it is necessary to understand the surrounding cultural issues to properly convey bad news. The purpose of the study was to explore Ethiopian patients’ cultural preferences for receiving bad news in a palliative care setting.

Methods

A qualitative research approach and nonprobability, purposive sampling method were applied. In-depth interviews were employed to collect data from eight patients who were diagnosed with cancer and cancer with HIV/AIDS during the time of data collection. Thematic analysis was applied to identify themes and subthemes. The data were transcribed verbatim and analysed using ATLAS.ti 22 computer software.

Results

The following three themes emerged and are reported in this study: (1) Perceptions about life-threatening illness: religious values and rituals are essential for establishing perspectives on life-threatening illnesses and preferences in receiving bad news. (2) Experiences with life-threatening illness: study participants’ experience with the method of breaking bad news was sad, and they were not provided with sufficient details about their medical condition. Making appropriate decisions, fulfilling the ordinance of religious faith, and avoiding unnecessary costs were outlined as benefits of receiving bad news. (3) Preferred ways of breaking bad news; the findings revealed that incremental, amiable and empathic methods for delivering bad news were preferred. It was suggested that the presence of family members is crucial when receiving bad news.

Conclusion

Patients choose to be told about their medical conditions in the presence of their family. However, the patient’s needs for receiving bad news were unmet. Patients should be involved in the treatment decision process. Delivery of bad news needs to tailor the preferred methods, cultural values, and religious beliefs. Delivering bad news according to the patients’ preferences helps to fulfil their wishes in palliative care.
Water intake and recurrent urinary tract infections prevention: economic impact analysis in seven countries
Authors: Zemdegs Juliane , Iroz Alison , Vecchio Mariacristina , Roze Stephane , Lotan Yair
Published: November 2023

Background

To estimate the economic impact of preventing urinary tract infections (UTI) by increasing water intake among women with recurrent UTI and low fluid intake across seven countries: France, United Kingdom, Spain, United States of America, Mexico, China and Australia.

Methods

A Markov model was developed to compare costs and outcomes of UTIs associated with low fluid intake in women versus a strategy of primary prevention by increasing water intake. Model inputs were based on randomized controlled trial data which found that increasing water intake by 1.5 L/day decreased the risk of developing cystitis by 48% in women with low fluid intake and recurrent UTI. A time horizon of 10 years was used; outcomes were from the payer perspective and included both direct and indirect costs, reported in 2019 United States dollars ($). Discounting rates varied by country. Scenarios of increasing levels of compliance to the increased water intake strategy were evaluated.

Results

The total cost of one UTI episode, including diagnostics, treatment and complications, ranged from $2164 (Mexico) to $7671 (Australia). Assuming 80% compliance with the increased water intake strategy over a 10-year time horizon, the number of UTIs prevented ranged from 435,845 (Australia) to 24150,272 (China), resulting in total savings of 286 million (Australia) to $4.4 billion (China). Across all countries, increased water intake resulted in lower cost and fewer UTIs compared with low water intake.

Conclusion

Preventing recurrent UTIs by increasing water intake would reduce both the clinical and economic burden associated with UTI. Public, healthcare professionals and patients should be made aware about the preventive positive impact of appropriate water intake on UTIs.
Six-hour time-restricted feeding inhibits lung cancer progression and reshapes circadian metabolism
Authors: Shi Dan , Fang Gaofeng , Chen Qianyao , Li Jianling , Ruan Xiongzhong , Lian Xuemei
Published: November 2023

Background

Accumulating evidence has suggested an oncogenic effect of diurnal disruption on cancer progression. To test whether targeting circadian rhythm by dietary strategy suppressed lung cancer progression, we adopted 6-h time-restricted feeding (TRF) paradigm to elucidate whether and how TRF impacts lung cancer progression.

Methods

This study used multiple lung cancer cell lines, two xenograft mouse models, and a chemical-treated mouse lung cancer model. Stable TIM-knockdown and TIM-overexpressing A549 cells were constructed. Cancer behaviors in vitro were determined by colony formation, EdU proliferation, wound healing, transwell migration, flow cytometer, and CCK8 assays. Immunofluorescence, pathology examinations, and targeted metabolomics were also used in tumor cells and tissues. mCherry-GFP-LC3 plasmid was used to detect autophagic flux.

Results

We found for the first time that compared to normal ad libitum feeding, 6-h TRF inhibited lung cancer progression and reprogrammed the rhythms of metabolites or genes involved in glycolysis and the circadian rhythm in tumors. After TRF intervention, only timeless (TIM) gene among five lung cancer-associated clock genes was found to consistently align rhythm of tumor cells to that of tumor tissues. Further, we demonstrated that the anti-tumor effect upon TRF was partially mediated by the rhythmic downregulation of the TIM and the subsequent activation of autophagy. Combining TRF with TIM inhibition further enhanced the anti-tumor effect, comparable to treatment efficacy of chemotherapy in xenograft model.

Conclusions

Six-hour TRF inhibits lung cancer progression and reshapes circadian metabolism, which is partially mediated by the rhythmic downregulation of the TIM and the subsequent upregulation of autophagy.
Establishment and application of an iELISA detection method for measuring apical membrane antigen 1 (AMA1) antibodies of Toxoplasma gondii in cats
Authors: Gao Yafan , Shen Yu , Fan Jiyuan , Ding Haojie , Zheng Bin , Yu Haijie , Huang Siyang , Kong Qingming , Lv Hangjun , Zhuo Xunhui , Lu Shaohong
Published: November 2023

Background

Diseases caused by Toxoplasma gondii (T. gondii) have introduced serious threats to public health. There is an urgent need to develop a rapid detection method for T. gondii infection in cats, which are definitive hosts. Recombinant apical membrane antigen 1 (rAMA1) was produced in a prokaryotic expression system and used as the detection antigen. The aim of this study was to evaluate and optimize a reliable indirect enzyme-linked immunosorbent assay (iELISA) method based on rAMA1 for the detection of antibodies against T. gondii in cats.

Results

The rAMA1-iELISA method was developed and optimized by the chessboard titration method. There were no cross-reactions between T. gondii-positive cat serum and positive serum for other pathogens, indicating that rAMA1-iELISA could only detect T. gondii in most cases. The lowest detection limit of rAMA1-iELISA was 1:3200 (dilution of positive serum), and the CV of repeated tests within batches and between batches were confirmed to be less than 10%. The results of 247 cat serum samples detected by rAMA1-iELISA (kappa value = 0.622, p < 0.001) were in substantial agreement with commercial ELISA. The ROC curve analysis revealed the higher overall check accuracy of rAMA1-iELISA (sensitivity = 91.7%, specificity = 93.6%, AUC = 0.956, 95% CI 0.905 to 1.000) than GRA7-based iELISA (sensitivity = 91.7%, specificity = 85.5%, AUC = 0.936, 95% CI 0.892 to 0.980). Moreover, the positive rate of rAMA1-iELISA (6.5%, 16/247) was higher than that of GRA7-based iELISA (3.6%, 9/247) and that of commercial ELISA kit (4.9%, 12/247).

Conclusion

The iELISA method with good specificity, sensitivity, and reproducibility was established and can be used for large-scale detection of T. gondii infection in clinical cat samples.
Non-coding RNA-mediated endothelial-to-mesenchymal transition in human diabetic cardiomyopathy, potential regulation by DNA methylation
Authors: Wang Eric , Chen Shali , Wang Honglin , Chen Tori , Chakrabarti Subrata
Published: November 2023

Aims

Diabetic cardiomyopathy (DCM) is a major complication of diabetes and a risk factor for cardiovascular disease. Endothelial dysfunction is central to DCM, and endothelial-to-mesenchymal transition (EndMT) is a key form of endothelial dysfunction in diabetes. EndMT in DCM has been well-studied in model systems and has been found to be epigenetically regulated by non-coding RNAs (ncRNAs). However, EndMT in DCM and its associated epigenetic changes need further characterization in human patients. It is also not known if ncRNAs are affected by changes in DNA methylation in DCM. This study aims to confirm in human hearts, the findings from animal and cell studies, and potentially provide novel insight into interactions between DNA methylation and ncRNAs in EndMT in DCM.

Methods and results

Heart tissues were collected from autopsy patients, fixed in formalin, and embedded in paraffin. Thin sections from paraffin-embedded tissues were used for histology and immunofluorescence analyses, where we confirmed that diabetic patients showed increased cardiac fibrosis that EndMT had occurred. Tissue curls from the paraffin-embedded tissues were used for RT-qPCR and methylation analyses. RT-qPCR quantitatively showed that EndMT occurs in the hearts of diabetics, and that EndMT in human hearts corresponded to changes in key ncRNAs. Methylation analysis showed that some of the EndMT-related ncRNAs were regulated by DNA promoter methylation, while others may be regulated through different epigenetic mechanisms.

Conclusions

We show that EndMT is a relevant pathological process in human hearts during DCM, and that its occurrence coincides with changes in relevant ncRNAs. We further find that interplay between DNA methylation and certain ncRNAs involved in the regulation of EndMT may contribute to the observed changes in ncRNA expression. These findings reinforce the role of EndMT in patients afflicted with DCM and underscore the complexities and importance of the interactions between different facets of epigenetic regulation.
Community perception of the autodissemination of pyriproxyfen for controlling malaria vectors in south-eastern Tanzania
Authors: Tarimo Felista S. , Dillip Angel , Kosia Efraim M. , Lwetoijera Dickson W.
Published: November 2023

Background

The efficacy of the autodissemination of pyriproxyfen to control malaria vectors has been demonstrated under semi field environment in Tanzania. However, the information on how best communities should be engaged for its routine and large-scale adoption are lacking. This study assessed the community’s level of knowledge, perceptions, acceptability of the autodissemination of pyriproxyfen, and the perceived risks on the safety of pyriproxyfen on the environment.

Methods

This was a concurrent mixed methods study, comprised of a community-based survey of 400 household representatives and eight focus group discussions (FGDs). The study was conducted in two villages in Mlimba district in south-eastern Tanzania between June and August 2022. For the quantitative data analysis, descriptive statistics were applied using R software, while inductive approach was used for qualitative data analysis, using NVivo software.

Results

Knowledge on autodissemination of pyriproxyfen approach was found to be relatively low among both the FGD respondents and surveyed community members (36%, n = 144). Nevertheless, when it was explained to them, the envisioned community support for the autodissemination approach was relatively high (97%, n = 388). One of the major perceived benefits of the autodissemination of pyriproxyfen was the reduction of malaria-transmitting mosquitoes and associated malaria transmission. Environmental impact of pyriproxyfen on non-target organisms and health risk to children were among the major concerns. When provided with information on the safety and its utilization particularly through autodissemination approach, 93.5% (n = 374) of the survey respondents said that they would allow the PPF-contaminated pots to be placed around their homes. Similarly, FGD respondents were receptive towards the autodissemination of pyriproxyfen, but emphasized on the need for raising awareness among community members before related field trials.

Conclusion

This study indicates a low knowledge but high support for scaling up of the autodissemination of pyriproxyfen as a complementary tool for malaria control in rural Tanzania. The Findings of this study suggest that community sensitization activities are required to improve the community’s acceptability and trust of the approach before respective field trials.
Sodium butyrate alleviates R97-116 peptide-induced myasthenia gravis in mice by improving the gut microbiota and modulating immune response
Authors: Sun Jing , Chen Juanjuan , Xie Qinfang , Sun Mengjiao , Zhang Wenjing , Wang Hongxia , Liu Ning , Wang Qi , Wang Manxia
Published: November 2023

Fermented butyrate exhibits an anti-inflammatory response to maintain immune homeostasis within the gut. However, the effect and underlying mechanism of butyrate on myasthenia gravis (MG) remain unclear. The changes in the gut microbiota and fecal contents of SCFAs in MG patients were examined. R97-116 peptide was used to induce the experimental autoimmune myasthenia gravis (EAMG) mice and sodium butyrate (NaB) was gavaged to the EAMG mice. Gut microbiota, the frequency of Th1, Th17, Treg, Tfh, and B cells, the levels of IFN-γ, IL-17 A, IL-10, IL-21, and anti-R97-116 IgG, RNA-seq of total B cells in the spleen were explored by metagenomics, flow cytometry, ELISA, and transcriptomics. A significant reduction in SCFA-producing bacteria including Butyricimonas synergistica and functional modules including butyrate synthesis/production II was observed in MG patients and fecal SCFAs detection confirmed the increase. The EAMG mice were successfully constructed and NaB supplementation has changed the composition and function of the gut microbiota. The numbers of Th1, Th17, Tfh, and B cells were significantly increased while that of Treg cells was obviously decreased in EAMG mice compared with controls. Interestingly, NaB treatment has reduced the amounts of Th17, Tfh, and B cells but increased that of Treg cells. Accordingly, the levels of IL-17 A, IL-21, and IgG were increased while IL-10 was decreased in EAMG mice. However, NaB treatment reduced IL-17 A and IL-21 but increased that of IL-10. RNA-seq of B cells has revealed 4577 deferentially expressed genes (DEGs), in which 1218 DEGs were up-regulated while 3359 DEGs were down-regulated in NaB-treated EAMG mice. GO enrichment and KEGG pathway analysis unveiled that the function of these DEGs was mainly focused on immunoglobulin production, mitochondrial respiratory chain complex, ribosome, oxidative phosphorylation, and CNS diseases including amyotrophic lateral sclerosis. We have found that butyrate was significantly reduced in MG patients and NaB gavage could evidently improve MG symptoms in EAMG mice by changing the gut microbiota, regulating the immune response, and altering the gene expression and function of B cells, suggesting NaB might be a potential immunomodulatory supplement for MG drugs.
Function and regulation of RGS family members in solid tumours: a comprehensive review
Authors: Yang Chenglong , Zhang Xiaoyuan , Yang Xiaowen , Lian Fuming , Sun Zongrun , Huang Yongming , Shen Wenzhi
Published: November 2023

G protein-coupled receptors (GPCRs) play a key role in regulating the homeostasis of the internal environment and are closely associated with tumour progression as major mediators of cellular signalling. As a diverse and multifunctional group of proteins, the G protein signalling regulator (RGS) family was proven to be involved in the cellular transduction of GPCRs. Growing evidence has revealed dysregulation of RGS proteins as a common phenomenon and highlighted the key roles of these proteins in human cancers. Furthermore, their differential expression may be a potential biomarker for tumour diagnosis, treatment and prognosis. Most importantly, there are few systematic reviews on the functional/mechanistic characteristics and clinical application of RGS family members at present. In this review, we focus on the G-protein signalling regulator (RGS) family, which includes more than 20 family members. We analysed the classification, basic structure, and major functions of the RGS family members. Moreover, we summarize the expression changes of each RGS family member in various human cancers and their important roles in regulating cancer cell proliferation, stem cell maintenance, tumorigenesis and cancer metastasis. On this basis, we outline the molecular signalling pathways in which some RGS family members are involved in tumour progression. Finally, their potential application in the precise diagnosis, prognosis and treatment of different types of cancers and the main possible problems for clinical application at present are discussed. Our review provides a comprehensive understanding of the role and potential mechanisms of RGS in regulating tumour progression.
Neurovascular unit disruption and blood–brain barrier leakage in MCT8 deficiency
Authors: Guillén-Yunta Marina , Valcárcel-Hernández Víctor , García-Aldea Ángel , Soria Guadalupe , García-Verdugo José Manuel , Montero-Pedrazuela Ana , Guadaño-Ferraz Ana
Published: November 2023

Background

The monocarboxylate transporter 8 (MCT8) plays a vital role in maintaining brain thyroid hormone homeostasis. This transmembrane transporter is expressed at the brain barriers, as the blood–brain barrier (BBB), and in neural cells, being the sole known thyroid hormone-specific transporter to date. Inactivating mutations in the MCT8 gene (SLC16A2) cause the Allan-Herndon-Dudley Syndrome (AHDS) or MCT8 deficiency, a rare X-linked disease characterized by delayed neurodevelopment and severe psychomotor disorders. The underlying pathophysiological mechanisms of AHDS remain unclear, and no effective treatments are available for the neurological symptoms of the disease.

Methods

Neurovascular unit ultrastructure was studied by means of transmission electron microscopy. BBB permeability and integrity were evaluated by immunohistochemistry, non-permeable dye infiltration assays and histological staining techniques. Brain blood-vessel density was evaluated by immunofluorescence and magnetic resonance angiography. Finally, angiogenic-related factors expression was evaluated by qRT-PCR. The studies were carried out both in an MCT8 deficient subject and Mct8/Dio2KO mice, an AHDS murine model, and their respective controls.

Results

Ultrastructural analysis of the BBB of Mct8/Dio2KO mice revealed significant alterations in neurovascular unit integrity and increased transcytotic flux. We also found functional alterations in the BBB permeability, as shown by an increased presence of peripheral IgG, Sodium Fluorescein and Evans Blue, along with increased brain microhemorrhages. We also observed alterations in the angiogenic process, with reduced blood vessel density in adult mice brain and altered expression of angiogenesis-related factors during brain development. Similarly, AHDS human brain samples showed increased BBB permeability to IgG and decreased blood vessel density.

Conclusions

These findings identify for the first time neurovascular alterations in the MCT8-deficient brain, including a disruption of the integrity of the BBB and alterations in the neurovascular unit ultrastructure as a new pathophysiological mechanism for AHDS. These results open a new field for potential therapeutic targets for the neurological symptoms of these patients and unveils magnetic resonance angiography as a new non-invasive in vivo technique for evaluating the progression of the disease.
A novel artificial vertebral implant with Gyroid porous structures for reducing the subsidence and mechanical failure rate after vertebral body replacement
Authors: Shang Peng , Ma Benyuan , Hou Guanghui , Zhang Yihai , Cui Lunxu , Song Wanzhen , Liu Yancheng
Published: November 2023

Background

Prosthesis subsidence and mechanical failure were considered significant threats after vertebral body replacement during the long-term follow-up. Therefore, improving and optimizing the structure of vertebral substitutes for exceptional performance has become a pivotal challenge in spinal reconstruction.

Methods

The study aimed to develop a novel artificial vertebral implant (AVI) with triply periodic minimal surface Gyroid porous structures to enhance the safety and stability of prostheses. The biomechanical performance of AVIs under different loading conditions was analyzed using the finite element method. These implants were fabricated using selective laser melting technology and evaluated through static compression and subsidence experiments.

Results

The results demonstrated that the peak stress in the Gyroid porous AVI was consistently lower than that in the traditional porous AVI under all loading conditions, with a maximum reduction of 73.4%. Additionally, it effectively reduced peak stress at the bone-implant interface of the vertebrae. Static compression experiments demonstrated that the Gyroid porous AVI was about 1.63 times to traditional porous AVI in terms of the maximum compression load, indicating that Gyroid porous AVI could meet the safety requirement. Furthermore, static subsidence experiments revealed that the subsidence tendency of Gyroid porous AVI in polyurethane foam (simulated cancellous bone) was approximately 15.7% lower than that of traditional porous AVI.

Conclusions

The Gyroid porous AVI exhibited higher compressive strength and lower subsidence tendency than the strut-based traditional porous AVI, indicating it may be a promising substitute for spinal reconstruction.
LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment
Authors: Hu Yi-dou , Wu Ke , Liu Yuan-jie , Zhang Qian , Shen Hui , Ji Jin , Fang Dong , Xi Song-yang
Published: November 2023

Background

Malignant melanoma is a highly heterogeneous skin cancer with the highest mortality rate among dermatological cancers. Catenins form functional networks in the nucleus to regulate gene expression and determine cell fate. Dysregulation of catenin expression correlates with the malignant characteristics of the tumor. We aimed to investigate the regulatory mechanisms of catenins in melanoma and to further define the function of catenin-related molecular signaling in the tumor microenvironment.

Methods

In this study, a bioinformatics approach combined with experimental validation was used to explore the potential tumor biology mechanisms of catenin-related signaling.

Results

Melanoma patients can be divided into two catenin clusters. Patients defined by high Junction Plakoglobin (JUP), Plakophilin 1 (PKP1), Plakophilin 3 (PKP3) levels (C2) had shorter survival time than other patients (C1). We demonstrated that JUP regulates Anterior Gradient 2 (AGR2)/LY6/PLAUR Domain Containing 3 (LYPD3) to maintain melanoma stemness and promotes glycolysis. We also found that LYPD3 was co-expressed with S100A9 and associated with immunosuppressive tumor microenvironment (TME).

Conclusion

The JUP/AGR2/LYPD3 signaling axis plays an important role in the malignant features of melanoma. Targeting the JUP/AGR2/LYPD3 signaling axis can help develop promising drugs.
AKT1 induces Nanog promoter in a SUMOylation-dependent manner in different pluripotent contexts
Authors: Francia Marcos Gabriel , Verneri Paula , Oses Camila , Vazquez Echegaray Camila , Garcia Mora Reneé , Toro Ayelen , Levi Valeria , Guberman Alejandra Sonia
Published: November 2023

AKT/PKB is a kinase crucial for pluripotency maintenance in pluripotent stem cells. Multiple post-translational modifications modulate its activity. We have previously demonstrated that AKT1 induces the expression of the pluripotency transcription factor Nanog in a SUMOylation-dependent manner in mouse embryonic stem cells. Here, we studied different cellular contexts and main candidates that could mediate this induction. Our results strongly suggest the pluripotency transcription factors OCT4 and SOX2 are not essential mediators. Additionally, we concluded that this induction takes place in different pluripotent contexts but not in terminally differentiated cells. Finally, the cross-matching analysis of ESCs, iPSCs and MEFs transcriptomes and AKT1 phosphorylation targets provided new clues about possible factors that could be involved in the SUMOylation-dependent Nanog induction by AKT.
Semi-tensor product-based one-bit compressed sensing
Authors: Hou Jingyao , Liu Xinling
Published: November 2023

The area of one-bit compressed sensing (1-bit CS) focuses on the recovery of sparse signals from binary measurements. Over the past decade, this field has witnessed the emergence of well-developed theories. However, most of the existing literature is confined to fully random measurement matrices, like random Gaussian and random sub-Gaussian measurements. This limitation often results in high generation and storage costs. This paper aims to apply semi-tensor product-based measurements to 1-bit CS. By utilizing the semi-tensor product, this proposed method can compress high-dimensional signals using lower-dimensional measurement matrices, thereby reducing the cost of generating and storing fully random measurement matrices. We propose a regularized model for this problem that has a closed-form solution. Theoretically, we demonstrate that the solution provides an approximate estimate of the underlying signal with upper bounds on recovery error. Empirically, we conduct a series of experiments on both synthetic and real-world data to demonstrate the proposed method’s ability to utilize a lower-dimensional measurement matrix for signal compression and reconstruction with enhanced flexibility, resulting in improved recovery accuracy.
Carotid atherosclerosis in a sample of Egyptian patients with or without ischemic vascular events
Authors: Elhfnawy Ahmed , Galeel Aya Abdel , Abdelkhalek Hazem
Published: November 2023

Background

Ethnic-racial factors are related to the development of extra- and intracranial atherosclerosis. There are extensive data about carotid atherosclerosis from American, European and Asian population. However, data from Egyptian ethnics are extremely rare. We aimed to examine the frequency and determine the predictors of carotid atherosclerosis in a sample of Egyptian patients. In a cross-sectional observational study, we prospectively recruited consecutive patients, with or without ischemic vascular events, either ischemic stroke or transient ischemic attack, who received neurovascular ultrasound in a tertiary hospital. We assessed the presence of carotid plaques and the degree of stenosis according to the hemodynamic North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.

Results

A total of 668 carotid arteries in 334 patients with a mean (IQR) age of 61 (55–70) years were examined; 69.5% presented with and 30.5% without ischemic vascular events. We found carotid plaques in 208 (31.1%) arteries among 147 (44%) patients; 32% of the patients showed non-hemodynamically significant plaques, whereas 3.6% showed 20–40% internal carotid artery (ICA) stenosis and 8.4% showed ≥ 50% ICA stenosis. In patients with ischemic vascular events and at least one risk factor, we detected carotid atherosclerosis, 20–40% ICA stenosis and ≥ 50% ICA stenosis in 40.4%, 3% and 9.1% among patients ≤ 60 years as well as in 64.8%, 5.5% and 13% among patients > 60 years, respectively. In an age and sex adjusted binary logistic regression model, the following factors predicted carotid atherosclerosis: age > 60 years (OR 3.33, 95% CI 1.99–5.57, p < 0.001), hypertension (OR 2.3, 95% CI 1.32–4.02, p = 0.003), current smoking (OR 2.27, 95% CI 1.13–4.55, p = 0.02), diabetes mellitus (OR 2.15, 95% CI 1.27–3.64, p = 0.004) and ischemic vascular events (OR 1.8, 95% CI 1.01–3.19, p = 0.046).

Conclusions

Among Egyptians, the frequency of carotid atherosclerosis seems to be low. Further multiethnic studies are warranted to compare the prevalence of carotid atherosclerosis among Egyptians with Whites and Chinese populations. Older age, hypertension, smoking, diabetes mellitus and ischemic vascular events are predictors of carotid atherosclerosis.
Evolution of blockchain consensus algorithms: a review on the latest milestones of blockchain consensus algorithms
Authors: Hussein Ziad , Salama May A. , El-Rahman Sahar A.
Published: November 2023

Blockchain technology has gained widespread adoption in recent years due to its ability to enable secure and transparent record-keeping and data transfer. A critical aspect of blockchain technology is the use of consensus algorithms, which allow distributed nodes in the network to agree on the state of the blockchain. In this review paper, we examine various consensus algorithms that are used in blockchain systems, including proof-of-work, proof-of-stake, and hybrid approaches. We go over the trade-offs and factors to think about when choosing a consensus algorithm, such as energy efficiency, decentralization, and security. We also look at the strengths and weaknesses of each algorithm as well as their potential impact on the scalability and adoption of blockchain technology.
Effect of phototherapy on eosinophils count in neonatal hyperbilirubinemia (cross-sectional study)
Authors: Tarek Sara , Mosallam Dalia S. , Saber Doaa , Diaa Nehal , Dayem Omnia Y. Abd El , Abdelmonem Samira
Published: November 2023

Background

Neonatal jaundice is a common disorder in neonates. Phototherapy is associated with various side effects despite being safe. This research aimed to determine the impact of phototherapy (PT) on eosinophil levels in neonates treated for unconjugated hyperbilirubinemia.

Methods

In this cross-sectional prospective study, icteric neonates admitted to the Neonatal Intensive Care Unit (NICU) of Abo-Elreesh Child Hospital, Cairo University, from July 2020 to June 2021 were assessed. Laboratory data, including serum bilirubin and blood cell differentiation for eosinophils before and after phototherapy, were collected, and demographic data like age, gender, gestational age, and duration of phototherapy were taken.

Results

Two hundred neonates were included in this study. Hyperbilirubinemia was most frequently related to ABO group incompatibility (44.5%). After phototherapy, total serum bilirubin and neutrophil levels were significantly decreased, and platelet levels were significantly increased. Eosinophil count and percent were significantly increased (p < 0.001) following phototherapy. A statistically significant positive correlation was found between eosinophil count before and after PT (r = 0.583, p < 0.001) and between eosinophil percent before and after PT (r = 0.617, p < 0.001).

Conclusion

Serum eosinophils were increased after phototherapy in icteric neonates with hyperbilirubinemia.
A novel approach to spontaneous retropharyngeal hematoma—a case report
Authors: Casanova Maria Jorge , Lino João , Magalhães António , Meireles Luís
Published: November 2023

Background

Retropharyngeal hematoma is a rare but life-threatening situation and may require emergency tracheostomy or surgical drainage if the airway is compromised. We present a case of a retropharyngeal hematoma with shown active submucosal bleeding and describe the novel approach taken for compression and control of the hemorrhage.

Case presentation

A 76-year-old man presented to our institution complaining of dysphagia and pharyngeal discomfort hematoma since that morning. The laryngoscopy showed a hematoma of the posterior wall of the hypopharynx. A computerized tomography scan with contrast was done, demonstrating a collection in the retropharyngeal space, and a small active vessel could be identified.

The patient was intubated, and compression was performed in the location of the retropharyngeal hematoma using the esophageal balloon of a Blakemore tube, with successful control of the active bleed.

Conclusions

Retropharyngeal hematoma can be fatal, and we present a unique solution that can be used to successfully stop the bleeding while avoiding more invasive strategies, by performing compression with a Blakemore esophageal balloon to stop the bleeding.
Common mental health disorders and cognitive decline in a longitudinal Down syndrome cohort
Authors: Idris Mina , Saini Fedal , Pape Sarah E. , Baksh R. Asaad , Cahart Marie-Stephanie , Strydom André
Published: November 2023

Background

Down syndrome is the most common genetic cause of intellectual disability and Alzheimer's disease. In the general population, common mental disorders (CMDs), including anxiety, depression and obsessive–compulsive disorder, are linked to cognitive decline and higher risk for dementia. It is not known how CMDs affect longer-term cognitive outcomes in Down syndrome, and there is often diagnostic uncertainty in older people with Down syndrome and psychiatric comorbidity.

Aims

To study the influence of CMDs on cognitive ability and whether they are related longitudinally to development of clinical signs of Alzheimer's disease in Down syndrome.

Method

We followed 115 individuals with Down syndrome, 27 of whom were diagnosed with a CMD, over approximately 3 years. Changes in cognitive and behavioural outcomes between baseline and follow-up assessment were analysed, with comparisons made between those with and without a comorbid CMD. Age, gender, apolipoprotein E status and level of intellectual disability were included as covariates.

Results

No significant association between presence of a CMD and poorer performance on cognitive tasks or informant-rated decline over time was observed (P > 0.05).

Conclusions

Our results suggest that a diagnosis of a CMD does not have a significant negative effect on long-term cognitive or behavioural outcomes in individuals with Down syndrome. In individuals with stable or treated CMD, subsequent cognitive decline is likely indicative of Alzheimer's disease rather than a consequence of mental disorder.
Psychological risk factors for Long COVID and their modification: study protocol of a three-arm, randomised controlled trial (SOMA.COV)
Authors: Engelmann Petra , Büchel Christian , Frommhold Jördis , Klose Hans F. E. , Lohse Ansgar W. , Maehder Kerstin , Nestoriuc Yvonne , Scherer Martin , Suling Anna , Toussaint Anne , Weigel Angelika , Zapf Antonia , Löwe Bernd
Published: November 2023

Background

Growing evidence suggests that in addition to pathophysiological, there are psychological risk factors involved in the development of Long COVID. Illness-related anxiety and dysfunctional symptom expectations seem to contribute to symptom persistence.

Aims

With regard to the development of effective therapies, our primary aim is to investigate whether symptoms of Long COVID can be improved by a targeted modification of illness-related anxiety and dysfunctional symptom expectations. Second, we aim to identify additional psychosocial risk factors that contribute to the persistence of Long COVID, and compare them with risk factors for symptom persistence in other clinical conditions.

Method

We will conduct an observer-blinded, three-arm, randomised controlled trial. A total of 258 patients with Long COVID will be randomised into three groups of equal size: targeted expectation management in addition to treatment as usual (TAU), non-specific supportive treatment plus TAU, or TAU only. Both active intervention groups will comprise three individual online video consultation sessions and a booster session after 3 months. The primary outcome is baseline to post-interventional change in overall somatic symptom severity.

Conclusions

The study will shed light onto the action mechanisms of a targeted expectation management intervention for Long COVID, which, if proven effective, can be used stand-alone or in the context of broader therapeutic approaches. Further, the study will enable a better understanding of symptom persistence in Long COVID by identifying additional psychological risk factors.
Nonalcoholic Fatty Liver Disease and the Risk of Thyroid Cancer Among Young Adults in South Korea
Authors: Kwon Hyemi , Han Kyung-Do , Moon Sun Joon , Park Se Eun , Rhee Eun-Jung , Lee Won-Young
Published: November 2023

Context

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Obesity and metabolic syndrome are known risk factors for thyroid cancer.

Objective

We investigated the association between NAFLD and thyroid cancer risk in young adults.

Methods

This nationwide cohort study included 1 135 967 participants aged 20 to 39 years who underwent 4 consecutive health screenings in South Korea. NAFLD was categorized using the fatty liver index (FLI), as follows: ≥60, 30 to 60, and <30. The cumulative FLI points were defined as the number of times participants had a FLI of ≥30 (0–4).

Results

During a median follow-up of 5.2 years, 4126 participants (0.36%) were newly diagnosed with thyroid cancer. Compared with the participants with an FLI of <30, those with an FLI of 30 to 60 (men: hazard ratio [HR] 1.36 [95% CI, 1.22-1.51] and women: HR 1.44 [1.21-1.70]) and those with an FLI of ≥60 (men: HR 1.71 [1.53-1.92] and women: HR 1.81 [1.46-2.25]) had a significantly higher risk of thyroid cancer. Participants with higher cumulative FLI points had a higher risk of thyroid cancer compared to those with a cumulative FLI point of 0 (P < .001). During the follow-up period, the participants with an increased FLI exhibited an increased risk of thyroid cancer.

Conclusion

NAFLD was associated with an increased risk of thyroid cancer in young adults. Repeatedly elevated FLI and progression of NAFLD were associated with an increased risk of thyroid cancer in this study.
Association of Urine Albumin to Creatinine Ratio With Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus
Authors: Zeng Cheng , Liu Maojun , Zhang Yifeng , Deng Simin , Xin Ying , Hu Xinqun
Published: November 2023

Context

The urinary albumin to creatinine ratio (UACR) is a widely used indicator of albuminuria and has predictive value for adverse cardiovascular events.

Objective

To evaluate the correlation between the UACR and the risk of developing major adverse cardiovascular events (MACEs) and total mortality in patients with type 2 diabetes mellitus (T2DM).

Methods

This post hoc analysis included 10 171 participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and the ACCORD follow-up study (ACCORDION) with baseline UACR data. The natural logarithm (ln) of each UACR measurement was calculated. Univariate and multivariate Cox proportional hazard regression analyses were conducted to examine the association between the UACR and the risk of MACEs and total mortality. The additional predictive value of UACR was further evaluated. Similar methods were used to analyze the correlation between the UACR and MACEs and total mortality within the normal range.

Results

During a median follow-up period of 8.83 years, 1808 (17.78%) participants experienced MACEs, and there were 1934 (19.01%) total deaths. After adjusting for traditional cardiovascular risk factors, the multivariate analysis revealed a significant association between the UACR and the risk of MACEs and total mortality. The inclusion of UACR in the conventional risk model enhanced the predictive efficacy for MACEs and total mortality.

Conclusion

An elevated UACR is associated with a higher risk of MACEs and total mortality in patients with T2DM, even when it falls within the normal range. The UACR improves prediction of MACE and total mortality risk in patients with T2DM.
Collective signalling drives rapid jumping between cell states
Authors: Westbrook Elizabeth R. , Lenn Tchern , Chubb Jonathan R. , Antolović Vlatka
Published: November 2023

Development can proceed in ‘fits and starts’, with rapid transitions between cell states involving concerted transcriptome-wide changes in gene expression. However, it is not clear how these transitions are regulated in complex cell populations, in which cells receive multiple inputs. We address this issue using Dictyostelium cells undergoing development in their physiological niche. A continuous single cell transcriptomics time series identifies a sharp ‘jump’ in global gene expression marking functionally different cell states. By simultaneously imaging the physiological dynamics of transcription and signalling, we show the jump coincides with the onset of collective oscillations of cAMP. Optogenetic control of cAMP pulses shows that different jump genes respond to distinct dynamic features of signalling. Late jump gene expression changes are almost completely dependent on cAMP, whereas transcript changes at the onset of the jump require additional input. The coupling of collective signalling with gene expression is a potentially powerful strategy to drive robust cell state transitions in heterogeneous signalling environments. Based on the context of the jump, we also conclude that sharp gene expression transitions may not be sufficient for commitment.