bluuebunny/crossref_metadata_2025 huggingface dataset:
Interprofessional Team Collaboration as a Mediator Between Workplace Social Capital and Patient Safety Climate: A Cross-Sectional Study
Authors: Kida Ryohei , Suzuki Risa , Fujitani Katsumi , Ichikawa Kaori , Matsushita Hironobu
Published: August 2023

Background and Objectives:

Patient-safety climate is one of the most important organizational factors contributing to health care quality. We hypothesized that a patient safety climate is fostered by the willingness to collaborate and trust among members as well as by daily collaborative practices. This study aimed to clarify the effect of workplace social capital on patient safety climate. We also sought to investigate the mediating effect of interprofessional team collaboration on the relationship between workplace social capital and patient safety climate.

Methods:

This cross-sectional survey was conducted from November 2021 to January 2022 using anonymous web-based questionnaires. The survey was distributed to 1495 employees working in a hospital in Tokyo, Japan. The questionnaire included the patient safety climate scale, workplace social capital scale, Japanese version of the Assessment of Interprofessional Team Collaboration Scale-II (AITCS-II-J), and demographic items. Structural equation modeling was performed to verify the associations among the 3 variables. In addition, a significance test for indirect effects was conducted using the bootstrap method to confirm the mediating effect of AITCS-II-J.

Results:

A total of 725 employees participated in this survey, and 632 data items were analyzed. Nurses were the highest number of respondents (68.2%), followed by physicians (13.3%). Workplace social capital and patient safety were directly and significantly associated (β = .309, P < .01). Furthermore, the partially indirect effect of the AITCS-II-J on the association between workplace social capital and patient safety climate was also significant (β = .430, P < .01).

Conclusions:

Workplace social capital was significantly and directly related to patient safety climate and was also significantly related to patient safety climate partially mediated by interprofessional team collaboration. Our findings suggest the importance of workplace social capital and routine multidisciplinary collaboration for a patient safety climate to manage health care quality.
Prostate Adenocarcinoma Metastasis to the Rectal Submucosa and Mesorectal Lymph Node on 18F-PSMA PET/CT
Authors: Segal Eric , Dababo Nour , Bhalla Deepali , Bucklan Daniel
Published: September 2023

We report a case of biopsy-proven prostate cancer metastasis to the rectum and presumed metastasis to a mesorectal lymph node, identified as radiotracer-avid lesions on prostate-specific membrane antigen PET/CT during workup for biochemically recurrent prostate cancer. This case adds to a growing number of atypical sites of metastatic prostate cancer being reported since the approval of prostate-specific membrane antigen PET/CT for staging of prostate cancer.
Goals of care and end-of-life communication needs of persons with chronic respiratory disease
Authors: Reinke Lynn F. , Fasolino Tracy , Sullivan Donald R.
Published: September 2023

Purpose of the review

To highlight recent advances in effective communication among persons with chronic respiratory diseases. The authors focus on communication science related to goals of care (GOC) discussions, medical devices, and life-sustaining invasive treatments. The authors discuss important considerations when working with individuals with low literacy and rurality. Communication handoffs between respiratory clinicians and/or palliative care to hospice clinicians are summarized to ensure effective person-centered and caregiver-centered care.

Recent findings

Studies suggest the following communication approaches: (1) clarify differences between palliative and end of life; (2) conduct conversations early and gradual throughout the illness trajectory; (3) distinguish types of GOC discussions as they relate to treatment preferences; (4) for patients from rural communities, include family members and spiritual leaders; (5) assess literacy and employ supportive strategies; (6) apply time-limited-trial framework for life-sustaining treatment (LST) decisions; and (7) standardize processes for communication handoffs to hospice clinicians to improve communication fidelity.

Effective communication tools for clinicians to engage in GOC discussions for persons with chronic respiratory diseases are grounded in a patient-centered framework. A trained clinician should lead these conversations and include interdisciplinary team members throughout the disease trajectory including at the end of life. These approaches may enable patients to express their values and care preferences as they evolve over time.
Rapid advancements in diagnostic technology during the COVID pandemic: Important and Difficult Tasks for Medical Laboratory Professionals
Authors: Khadka Ram Bahadur , Karki Khimdhoj , Pandey Jitendra , Chaudhary Gautam Prasad , Gupta Santosh Kumar , Dhakal Ganesh , Pant Dhakaraj
Published: September 2023

The acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the illness COVID-19 first emerged throughout China in December 2019 and subsequently spread throughout the globe after the World Health Organization designated it a global outbreak in March 2020.We used the terms COVID-19, SARS-COV-2, Medical Laboratory Professionals,Diagnostic, and Importance, difficulties to search the databases of PubMed and Google Scholar for previously published material. Many molecular based diagnostic tests are applied in corona virus detection like Reverse Transcription Polymerase Chain Reaction, Multiplex Polymerase Chain Reaction, Droplet Digital polymerase Chain reaction, Loop-mediated Isothermal Amplification Test and more. Due to lack of availability of molecular and serologic tests that have been clinically validated or authorized by national or international regulatory bodies, Clinical laboratory experts are tackling threats to our global defense and wellness, including infectious diseases. The opportunity to express gratitude to the unsung medical laboratory heroes and COVID0-19 pandemic allies is now greater than ever. Each year, Medical Laboratory Professionals Week should honors those who contribute key diagnostic data that help save lives. This review article explore overall summary on testing methods including Important and Difficult Tasks for Medical Laboratories which will provide good message for better public health matter.
The Association of Alzheimer’s Disease-related Blood-based Biomarkers with Cognitive Screening Test Performance in the Congolese Population in Kinshasa
Authors: Schwinne Megan , Alonso Alvaro , Roberts Blaine R. , Hickle Sabrina , Verberk Inge MW , Epenge Emmanuel , Gikelekele Guy , Tsengele Nathan , Kavugho Immaculee , Mampunza Samuel , Yarasheski Kevin E. , Teunissen Charlotte E. , Stringer Anthony , Levey Allan , Ikanga Jean
Published: September 2023

Background

Alzheimer’s Disease (AD), the most common cause of dementia, poses a significant global burden. Diagnosis typically involves invasive and costly methods like neuroimaging or cerebrospinal fluid (CSF) biomarker testing of phosphorylated tau (p-tau) and amyloid-β42/40(Aβ42/40). Such procedures are especially impractical in resource-constrained regions, such as the Democratic Republic of Congo (DRC). Blood-based biomarker testing may provide a more accessible screening opportunity.

Objective

This study aims to examine if AD-related blood-based biomarkers are associated with cognitive test performance in the Congolese population, where limited research has been conducted.

Methods

In this cross-sectional study of 81 Congolese individuals, cognitive assessments (Alzheimer’s Questionnaire (AQ) and Community Screening Interview for Dementia (CSID)) distinguished dementia cases from controls. Blood draws were taken to assess p-tau 181 and Aβ42/40biomarkers. Relationships between the biomarkers and cognitive performance were analyzed using multiple linear regression models.

Results

Lower plasma Aβ42/40was significantly associated with lower CSID scores and higher AQ scores, indicative of AD (p<0.001). These relationships were observed in healthy controls (CSID p=0.01, AQ p=0.03), but not in dementia cases. However, p-tau 181 did not exhibit significant associations with either measure. Factors such as age, sex, education, presence of APOE e4 allele, did not alter these relationships.

Conclusion

Understanding relationships between AD-related screening tests and blood-biomarkers is a step towards utilization of blood-based biomarker tests as a screening tool for AD, especially in resource-limited regions. Further research should be conducted to evaluate blood biomarker test efficacy in larger samples and other populations.
Can long-term COVID-19 vaccination be improved by serological surveillance?: a modeling study for Mozambique
Authors: Liu Carol Y , Shioda Kayoko , Kraay Alicia NM , Massora Sergio , de Jesus Áuria , Massinga Arsénia , Monjane Celso , Omer Saad B , Jenness Samuel M , Nelson Kristin , Flasche Stefan , Mandomando Inacio , Lopman Benjamin A
Published: September 2023

Seroprevalence provides an estimate of the population-level susceptibility to infection. In this study, we used a transmission model to examine the potential of using serological surveillance to inform the timing of COVID-19 boosters in Mozambique. We simulated using population-level seroprevalence thresholds as an estimate of the risk of outbreaks to trigger the timing of re-vaccination campaigns among older adults. We compare this approach to a strategy of re-vaccination at fixed time intervals. Vaccinating older adults each time the seroprevalence among older adults falls below 50% and 80% resulted in medians of 20% and 71% reduction in deaths, respectively, and number-needed-to-vaccinate to avert one death (NNT) of 1,499 (2.5th-97.5thcentile:1,252-1,905) and 3,151 (2,943-3,429), respectively. In comparison, biennial and annual re-vaccination of older adults resulted in medians of 35% and 52% deaths averted, respectively, and NNTs of 1,443 (1,223-1,733) and 1,941 (1,805-2,112), respectively. We conducted sensitivity analysis over a range of antibody waning rates and epidemic scenarios and found that re-vaccination trigger thresholds of 50-60% seroprevalence are most likely to be efficient compared to fixed-time strategies. However, given marginal gains in efficiency even in the best-case scenarios, our results favor the use of simpler fixed-time strategies for long-term control of SARS-CoV-2.
PVN microglia via P2Y12transmit hemodynamic signal to promote sympathetic excitation in hypertension
Authors: Wei Bo , Cheng Guo , Li Li , Sun Qihang , Bi Qianqian , Lu Cheng , Yin Chunyou , Chen Ningting , Hu Miner , Lu Haoran , Hu Zhechun , Mao Genxiang , Gu Yan , Wan Shu , Liu Xiaoli , Shen Xiao Z. , Shi Peng
Published: September 2023

Hypertension is usually accompanied with an elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not fully understood. Recent advances reveal that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels, and found that microglia in the hypothalamic paraventricular nucleus (PVN) were early responders to hypertensive challenges. PVN is the central hub for maintaining cardiovascular function via regulation of fluid balance and sympathetic outflow. Comprehensive vasculature analyses unveiled that PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology among brain regions. As such, PVN is susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. ATP ligation to microglial P2Y12receptor is responsible for the microglial accumulation and activation in the PVN. Furthermore, either pharmacological blockade or genetic ablation of microglial P2Y12could substantially restrain blood pressure increase under hypertensive challenge. Together, these findings disclose that a unique vasculature pattern results in the vulnerability of PVN pre-sympathetic neurons to hypertension-associated insults, which is mediated by microglia.
PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression
Authors: Schmidt Christin , Cohen Sarah , Gudenas Brian L. , Husain Sarah , Carlson Annika , Westelman Samantha , Wang Linyu , Phillips Joanna J. , Northcott Paul A. , Weiss William A. , Schwer Bjoern
Published: September 2023

SNCAIPduplication may promote Group 4 medulloblastomaviainduction of PRDM6, a poorly characterized member of thePRDF1 and RIZ1 homology domain-containing(PRDM) family of transcription factors. Here, we investigated the function of PRDM6 in human hindbrain neuroepithelial stem cells and tested PRDM6 as a driver of Group 4 medulloblastoma. We report that human PRDM6 localizes predominantly to the nucleus, where it causes widespread repression of chromatin accessibility and complex alterations of gene expression patterns. Genome-wide mapping of PRDM6 binding reveals that PRDM6 binds to chromatin regions marked by histone H3 lysine 27 trimethylation that are located within, or proximal to, genes. Moreover, we show that PRDM6 expression in neuroepithelial stem cells promotes medulloblastoma. Surprisingly, medulloblastomas derived from PRDM6-expressing neuroepithelial stem cells match human Group 3, but not Group 4, medulloblastoma. We conclude that PRDM6 expression has oncogenic potential but is insufficient to drive Group 4 medulloblastoma from neuroepithelial stem cells. We propose that both PRDM6 and additional factors, such as specific cell-of-origin features, are required for Group 4 medulloblastoma. Given the lack of PRDM6 expression in normal tissues and its oncogenic potential shown here, we suggest that PRDM6 inhibition may have therapeutic value in PRDM6-expressing medulloblastomas.
A microfluidic model of colonocyte-microbiota interaction mimicking the colorectal cancer microenvironment
Authors: Penarete-Acosta Daniel , Stading Rachel , Emerson Laura , Horn Mitchell , Chakraborty Sanjukta , Han Arum , Jayaraman Arul
Published: September 2023

Changes in the abundance of certain bacterial species within the colorectal microbiota correlate with colorectal cancer development. While carcinogenic mechanisms of single pathogenic bacteria have been characterizedin vitro, limited tools are available to investigate interactions between pathogenic bacteria and both commensal microbiota and colonocytes in a physiologically relevant tumor microenvironment. To address this, we developed a microfluidic device that can be used to co-culture colonocytes and colorectal microbiota. The device was used to explore the effect ofFusobacterium nucleatum, an opportunistic pathogen associated with colorectal cancer development in humans, on colonocyte gene expression and microbiota composition.F. nucleatumaltered the transcription of genes involved in cytokine production, epithelial-to-mesenchymal transition, and proliferation in colonocytes in a contact-independent manner; however, most of these effects were diminished by the presence of fecal microbiota. Interestingly,F. nucleatumsignificantly altered the abundance of multiple bacterial clades associated with mucosal immune responses and cancer development in the colon. Our results highlight the importance of evaluating the potential carcinogenic activity of pathogens in the context of a commensal microbiota, and the potential to discover novel inter-species microbial interactions in the colorectal cancer microenvironment.
Effects of visual feedback on corticostriatal activity during continuousde novomotor skill learning
Authors: Park Sungbeen , Kim Junghyun , Kim Sungshin
Published: September 2023

A corticostriatal network plays a pivotal role in visuomotor learning. However, it is unclear to what extent visual feedback for motor learning impacts corticostriatal activity. To address this, we conducted an fMRI experiment in which participants acquired a complex motor skill using either online or offline visual cursor feedback. We found a highly selective response in the entire striatum to visual performance feedback in both conditions and a relatively higher response in the caudate nucleus for the offline feedback. However, the ventromedial prefrontal cortex (vmPFC) response was significant only for online feedback. Furthermore, we also found functional distinctions of the striatal subregions in random versus goal-directed motor control. These findings collectively underscore the substantial impact of such simple visual feedback, as designed in our study, in eliciting corticostriatal responses, thereby elucidating its significance in reinforcement-based motor learning.
Alterations in Sarcopenia Index are Associated with Inflammation, Gut and Oral Microbiota among Heart Failure, Left Ventricular Assist Device and Heart Transplant Patients
Authors: Yuzefpolskaya Melana , Bohn Bruno , Ladanyi Annamaria , Pinsino Alberto , Braghieri Lorenzo , Carey Matthew R. , Clerkin Kevin , Sayer Gabriel T. , Latif Farhana , Koji Takeda , Uriel Nir , Nandakumar Renu , Uhlemann Anne-Catrin , Colombo Paolo C. , Demmer Ryan T.
Published: September 2023

Background

Sarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and associated with poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate marker of skeletal muscle mass, in HF, left ventricular assist device (LVAD) and heart transplant (HT) and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota.

Methods

We enrolled 460 HF, LVAD and HT patients. Repeated measures pre and post procedures were obtained in a subset of LVAD and HT patients. Sarcopenia index (serum Creatinine/Cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S rRNA sequencing among 335 stool and 341 saliva samples. Multivariable regression models were used to assess the relationship between SI and i) New York Heart Association class; ii) pre-vs. post-LVAD or HT; iii) biomarkers of inflammation and microbial diversity.

Results

Median (interquartile range) ln-SI was −0.13(−0.32,0.05). Ln-SI decreased across worsening HF class, further declined within the 1-month after LVAD and HT and rebounded over time to the levels of symptomatic HF. Ln-SI demonstrated an inverse correlation with inflammation (r=-0.28, p<0.0001), and a positive correlation with gut (r=0.26, p<0.0001) and oral microbial diversity (r=0.24, p<0.0001). Presence of the gut taxaRoseburia inulinivoranswas associated with increased SI.

Conclusions

SI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. SI levels covaried with inflammation, gut and oral microbiota in a similar fashion.
From Fossils to Living Canids: Two Contrasting Perspectives on Biogeographic Diversification
Authors: Porto Lucas M. V. , Maestri Renan , Janzen Thijs , Etienne Rampal S.
Published: September 2023

The Canidae are an ecologically important group of dog-like carnivores that arose in North America and spread across the planet around 10 million years ago. The current distribution patterns of species, coupled with their phylogenetic structure, suggest that Canidae diversification may have occurred at varying rates across different biogeographic areas. However, such extant-only analyses undervalued the group’s rich fossil history because of a limitation in method’s development. Current State-dependent Speciation and Extinction (SSE) models are (i) often parameter-rich which hinders reliable application to relatively small clades such as the Caninae (the only extant subclade of the Canidae consisting of 36 extant species); and (ii) often assume as possible states only the states that extant species present. Here we extend the SSE method SecSSE to apply to phylogenies with extinct species as well (111 Caninae species) and compare the results to those of analyses with the extant-species-only phylogeny. The results on the extant-species tree suggest that distinct diversification patterns are related to geographic areas, but the results on the complete tree do not support this conclusion. Furthermore, our extant-species analysis yielded an unrealistically low estimate of the extinction rate. These contrasting findings suggest that information from extinct species is different from information from extant species. A possible explanation for our results is that extinct species may have characteristics (causing their extinction), which may be different from the characteristics of extant species that caused them to be extant. Hence, we conclude that differences in biogeographic areas probably did not contribute much to the variation in diversification rates in Caninae.
Evolution of hierarchical switching pattern in antigenic variation ofPlasmodium falciparumunder variable host immunity
Authors: Iragavarapu Gayathri Priya , Varsha HJ , Vembar Shruthi Sridhar , Ghosh Bhaswar
Published: September 2023

The var genes family encoding the variants of the erythrocyte membrane protein ofPlasmodium falciparumis crucial for virulence of the parasite inside host. The transcriptional output of the var genes switches from one variant to other in a mutually exclusive fashion. It is proposed that a biased hierarchical switching pattern optimizes the growth and survival of the parasite inside the host. Apart from the hierarchical switching pattern, it is also well established that the intrinsic switching rates vary widely among the var genes. The centromeric protein like Var2csa is much more stable than the genes located at the telomeric and sub-telomeric regions of the chromosomes. In this study, we explored the evolutionary advantage achieved through selecting variable switching rates. Our theoretical analysis based on a mathematical model coupled with single cell RNA-seq data suggests that the variable switching rate is beneficial when cells expressing different variants are deferentially amenable to be cleared by the immune response. In fact, the variants which are cleared by the immune systems more efficiently are more stably expressed compared to a variant attacked by the immune system much less vigorously. The cells turn off expression of the variant quickly which is not cleared very efficiently. The evolutionary simulation shows that this strategy maximizes the growth of the parasite population under the presence of immune attack by the host. In corroboration with the result, we observed that stable variant has higher binding affinity to IgM from experimental data. Our study provides an evolutionary basis of widely variable switching rates of the var genes inPlasmodium falciparum.
Using neural biomarkers to personalize dosing of vagus nerve stimulation
Authors: Berthon Antonin , Wernisch Lorenz , Stoukidi Myrta , Thornton Michael , Tessier-Lariviere Olivier , Fortier-Poisson Pascal , Mamen Jorin , Pinkney Max , Lee Susannah , Sarkans Elvijs , Annecchino Luca , Appleton Ben , Garsed Philip , Patterson Bret , Gonshaw Samuel , Jakopec Matjaz , Shunmugam Sudhakaran , Edwards Tristan , Tukiainen Aleksi , Jennings Joel , Lajoie Guillaume , Hewage Emil , Armitage Oliver
Published: September 2023

Background

Vagus nerve stimulation (VNS) is an established therapy for treating a variety of chronic diseases, such as epilepsy, depression, obesity, and for stroke rehabilitation. However, lack of precision and side-effects have hindered its efficacy and extension to new conditions.

Objective

To achieve a better understanding of the relationship between VNS parameters and neural and physiological responses to enable the design of personalized dosing procedures to improve precision and efficacy of VNS therapies.

Methods

We used biomarkers from recorded evoked neural activity and short-term physiological responses (throat muscle, cardiac and respiratory activity) to understand the response to a wide range of VNS parameters in anaesthetised pigs. Using signal processing, Gaussian processes (GP) and parametric regression models we analyse the relationship between VNS parameters and neural and physiological responses.

Results

Firstly, we observe inter-subject variability for both neural and physiological responses. Secondly, we illustrate how considering multiple stimulation parameters in VNS dosing can improve the efficacy and precision of VNS therapies. Thirdly, we describe the relationship between different VNS parameters and the evoked neural activity and show how spatially selective electrodes can be used to improve fibre recruitment. Fourthly, we provide a detailed exploration of the relationship between the activations of neural fibre types and different physiological effects, and show that recordings of evoked neural activity are powerful biomarkers for predicting the short-term physiological effects of VNS. Finally, based on these results, we discuss how recordings of evoked neural activity can help design VNS dosing procedures that optimize short-term physiological effects safely and efficiently.

Conclusion

Understanding of evoked neural activity during VNS provide powerful biomarkers that could improve the precision, safety and efficacy of VNS therapies.
Structural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1
Authors: Mycroft-West Courtney J. , Abdelkarim Sahar , Duyvesteyn Helen M. E. , Gandhi Neha S. , Skidmore Mark A. , Owens Raymond J. , Wu Liang
Published: September 2023

Heparan sulfate (HS) polysaccharides are major constituents of the extracellular matrix, involved in myriad structural and signaling processes. Mature HS polysaccharides contain complex, non-templated patterns of sulfation and epimerization, which mediate interactions with diverse protein partners. Complex HS modifications form around initial clusters of glucosamine-N-sulfate (GlcNS) on nascent polysaccharide chains, but the mechanistic basis underpinning incorporation of the GlcNS modification itself into HS remains unclear. We have determined cryo-electron microscopy structures of human N-deacetylase-N-sulfotransferase (NDST)1, the bifunctional enzyme responsible for initial GlcNS modification of HS. Our structures reveal the architecture of both NDST1 deacetylase and sulfotransferase catalytic domains, alongside a previously unreported non-catalytic N-terminal domain. Surprisingly, the two catalytic domains of NDST1 adopt an unusual back-to-back topology that limits direct cooperativity. Binding analyses, aided by novel activity modulating nanobodies, suggest that sulfotransferase domain substrate anchoring initiates the NDST1 catalytic cycle, providing a plausible mechanism for cooperativity despite spatial domain separation. Our data shed light on key determinants of NDST1 activity, and describe tools to probe NDST1 functionin vitroandin vivo.
Hsa_circ_0005397 could promote hepatocellular carcinoma progression and metastasis through EIF4A3
Authors: Yuan Liu-Xia , Luo Mei , Liu Ruo-Yu , Wang Hui-Xuan , Ju Lin-Ling , Wang Feng , Cao Li-Ya , Wang Zhong-Cheng , Chen Lin
Published: September 2023

Purpose

The purpose was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma metabolism.

Methods

The quantitative real-time PCR (qPCR) was used to measure the expression of hsa_circ_0005397 and EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. The ROC curve was draw to analysis clinical value. The actinomycin D assay and Nuclear and Cytoplasmic Extraction assay were utilized to evaluate the characteristic of hsa_circ_0005397. The CCK-8 and colony formation assays were performed to detect cell proliferation. The flow cytometry analysis was used to detect the cycle distribution. The transwell assays and Xenograft tumor model were conducted to explore cell metabolism. The RNA-binding proteins of hsa_circ_0005397 in HCC were explored in bioinformatics websites. The relationship between hsa_circ_0005397 and EIF4A3 was verified by RIP assays and rescue experiments.

Results

Hsa_circ_0005397 and EIF4A3 were overexpressed in HCC. Through ROC analysis, hsa_circ_0005397 shown a big role in diagnosis and prognosis. Hsa_circ_0005397 was stable and almost distributed in the cytoplasm. The upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, metastatic potency of HCC cells, while downregulation of hsa_circ_0005397 yielded opposite results. Tumor volume and size were notably reduced while downregulation of hsa_circ_0005397, showing significant difference in tumor growth. EIF4A3 was the RNA-binding protein of hsa_circ_0005397, the expression of hsa_circ_0005397 decreased equally when depletion of EIF4A3.

Knockdown of EIF4A3 could reverse the function on HCC progression.

Conclusions

Hsa_circ_0005397 could promote the progression of hepatocellular carcinoma through EIF4A3. These research findings may present a novel clinical value for HCC.
Altered DNA methylation underlies monocyte dysregulation and innate exhaustion memory in sepsis
Authors: Caldwell Blake A. , Wu Yajun , Wang Jing , Li Liwu
Published: September 2023

Innate immune memory is the process by which pathogen exposure elicits cell-intrinsic states to alter the strength of future immune challenges. Such altered memory states drive monocyte dysregulation during sepsis, promoting pathogenic behavior characterized by pro-inflammatory, immunosuppressive gene expression in concert with emergency hematopoiesis. Epigenetic changes, notably in the form of histone modifications, have been shown to underlie innate immune memory, but the contribution of DNA methylation to this process remains poorly understood. Using anex vivosepsis model, we discovered broad changes in DNA methylation throughout the genome of exhausted monocytes, including at several genes previously implicated as major drivers of immune dysregulation during sepsis and Covid-19 infection (e.g.Plac8). Methylome alterations are driven in part by Wnt signaling inhibition in exhausted monocytes, and can be reversed through treatment with DNA methyltransferase inhibitors, Wnt agonists, or immune training molecules. Importantly, these changes are recapitulated in septic mice following cecal slurry injection, resulting in stable changes at critical immune genes that support the involvement of DNA methylation in acute and long-term monocyte dysregulation during sepsis.
DESCRIPTION OF THE METABOLIC SYNDROME AND ITS INDIVIDUALIZED RISK IN A LATIN AMERICAN COHORT OF GERIATRIC PATIENTS WITH HYPOTHYROIDISM
Authors: Dulcey Sarmiento Luis Andres , Theran Leon Juan Sebastián , Gomez Jaime , Parales Strauch Rafael Guillermo , Caltagirone Raimondo , Blanco Pimiento Edgar Camilo , Ciliberti Artavia María Paula , Martinez Juan Camilo , Peña Valentina Cabrera , Amaya Maria Camila , Vargas Jorge Luis , Lizcano Angie , Quintero Aldahir , Mayorca Juan Camilo , Hernandez Carlos , Cala Maria Alejandra
Published: September 2023

Introduction

It is still discussed whether hypothyroidism as an independent risk factor for cardiovascular events. Our objective was to evaluate the association between hypothyroidism and the risks of cardiovascular events and mortality through 3 stratification systems.

Methods

A retrospective study was carried out by reviewing medical records in the period of January 2015 - December 2017 in a South American hospital. Patients had fasting total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and plasma glucose were included. Quantitative variables are presented as mean ± standard deviation or median (interquartile range) according to their distribution, and qualitative variables as percentages. Student’s test was performed to assess the differences between two variables. all statistical analyzes of the database results were performed with (SPSS for Windows, v.20.1; Chicago, IL).

Results

The present study has demonstrated metabolic syndrome criteria present in patients diagnosed with hypothyroidism in a high proportion. The male gender was 32% compared to the female 68%. The Framingham equation classified a higher percentage of women patients with hypothyroidism as low cardiovascular risk compared to the PROCAM and SCORE equations. Item was found that there was a greater cardiovascular risk in those patients with still uncontrolled hypothyroidism profile, showing a statistical correlation of this alteration for the 3 stratification systems used.

Conclusions

Hypothyroidism is a risk factor for cardiovascular disease. Uncontrolled hypothyroidism in the present study is associated with greater adverse outcomes in the medium and long term, the present study warns about the need to better characterize this patient cohorts.
Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies – an Interim Report
Authors: Stein Elisa , Heindrich Cornelia , Wittke Kirsten , Kedor Claudia , Kim Laura , Freitag Helma , Krueger Anne , Toelle Markus , Scheibenbogen Carmen
Published: September 2023

There is increasing evidence for an autoimmune aetiology in post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). SARS-CoV-2 has now become the main trigger for ME/CFS. We have already conducted two small proof-of-concept studies of IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients. This observational study aims to evaluate the efficacy of IA in patients with post-COVID-19 ME/CFS. The primary objective is to assess the improvement in functional ability. Due to the urgency of finding therapies for post-Covid-Syndrome (PCS), we report here the interim results of the first ten patients with seven responders defined by an increase of between 10 and 35 points in the Short-Form 36 Physical Function (SF36-PF) at week four after IA. The results of this observational study will provide the basis for patient selection for a randomised controlled trial (RTC) including sham apheresis and for a RTC combining IA with B-cell depletion therapy.
Alcohol consumption and heavy episodic drinking within different types of drinking occasion in Great Britain: An event-level latent class analysis
Authors: Holmes John , Sasso Alessandro , Alava Mónica Hernández , Neves Rita Borges , Stevely Abigail K , Warde Alan , Meier Petra S
Published: September 2023

Aims

To update a previous typology of British alcohol drinking occasions using a more recent and expanded dataset and revised modelling procedure. To estimate the average consumption level, prevalence of heavy drinking, and distribution of total alcohol consumption and heavy drinking within and across occasion types.

Design

Cross-sectional latent class analysis of event-level diary data.

Setting

Great Britain, 2019.

Cases

43,089 drinking occasions reported by 17,821 adult drinkers.

Measurements

The latent class indicators are characteristics of off-trade only (e.g. home), on-trade only (e.g. bar) and mixed trade (e.g. home and bar) drinking occasions. These describe companions, venue(s) and location, purpose, motivation, accompanying activities, timings, weekday, consumption volume in units (1 UK unit = 8g ethanol) and predominant beverage consumed.

Findings

Three latent class models identified four off-trade only occasion types (i.e. latent classes), eight on-trade only occasion types and three mixed-trade occasion types. Mean consumption per occasion varied between 4.4 units inFamily mealsto 17.7 units inBig nights out with pre-loading. Mean consumption exceeded ten units in all mixed-trade occasion types and inOff-trade get togethers, Big nights outandMale friends at the pub. Three off-trade occasion types accounted for 50.8% of all alcohol consumed and 51.8% of heavy drinking occasions:Quiet drink at home alone, Evening at home with partnerandOff-trade get togethers. For thirteen out of fifteen occasion types, more than 25% of occasions involved heavy drinking. Conversely, 41.7% ofBig nights outand 16.4% ofBig nights out with preloadingwere not heavy drinking occasions.

Conclusions

Alcohol consumption varies substantially across and within fifteen types of drinking occasion in Great Britain. Heavy drinking is common in most occasion types. However, moderate drinking is also common in types often characterised as heavy drinking practices. Mixed-trade drinking occasions are particularly likely to involve heavy drinking.
The impact of climate change and natural climate variability on the global distribution ofAedes aegypti
Authors: Kaye AR , Obolski U , Sun L , Hurrell JW , Tildesley MJ , Thompson RN
Published: September 2023

Aedes aegyptispread pathogens affecting humans, including the dengue, Zika and yellow fever viruses. Anthropogenic climate change is altering the spatial distribution ofAe. aegyptiand therefore the locations at risk of vector-borne disease. In addition to climate change, natural climate variability, resulting from internal atmospheric processes and interactions between climate system components (e.g. atmosphere-land, atmosphere-ocean) determines climate outcomes. However, the combined effects of climate change and natural climate variability on futureAe. aegyptispread have not been assessed fully. We developed an ecological model in whichAe. aegyptipopulation dynamics depend on climate variables (temperature and rainfall). We used 100 projections from the Community Earth System Model, a comprehensive climate model that simulates natural climate variability as well as anthropogenic climate change, in combination with our ecological model to generate a range of equally plausible scenarios describing the global distribution of suitable conditions forAe. aegyptiup to 2100. Like other studies, we project the poleward expansion ofAe. aegyptiunder climate change. However, the extent of spread varies considerably between projections, each under the same Shared Socioeconomic Pathway scenario (SSP3-7.0). For example, by 2100, climatic conditions in London may be suitable forAe. aegyptifor between one and five months in the year, depending on natural climate variability. Our results demonstrate that natural climate variability yields different possible futureAe. aegyptispread scenarios. This affects vector-borne disease risks, including the potential for some regions to experience outbreaks earlier than expected under climate change alone.
Investigating the relationship between extreme weather and cryptosporidiosis and giardiasis in Colorado: a multi-decade study using distributed-lag nonlinear models
Authors: Grover Elise N. , Crooks James L. , Carlton Elizabeth J. , Paull Sara H. , Allshouse William B. , Jervis Rachel H. , James Katherine A.
Published: September 2023

Environmentally-mediated protozoan diseases like cryptosporidiosis and giardiasis are likely to be highly impacted by extreme weather, as climate-related conditions like temperature and precipitation have been linked to their survival, distribution, and overall transmission success. Our aim was to investigate the relationship between extreme temperature and precipitation and cryptosporidiosis and giardiasis infection using monthly weather data and case reports from Colorado counties over a twenty-one year period. Data on reportable diseases and weather among Colorado counties were collected using the Colorado Electronic Disease Reporting System (CEDRS) and the Daily Surface Weather and Climatological Summaries (Daymet) Version 3 dataset, respectively. We used a conditional Poisson distributed-lag nonlinear modeling approach to estimate the lagged association (between 0 and 12-months) between relative temperature and precipitation extremes and the risk of cryptosporidiosis and giardiasis infection in Colorado counties between 1997 – 2017, relative to the risk found at average values of temperature and precipitation for a given county and month. We found distinctly different patterns in the associations between temperature extremes and cryptosporidiosis, versus temperature extremes and giardiasis. When maximum or minimum temperatures were high (90thpercentile) or very high (95thpercentile), we found a significant increase in cryptosporidiosis risk, but a significant decrease in giardiasis risk, relative to risk at the county and calendar-month mean. Conversely, we found very similar relationships between precipitation extremes and both cryptosporidiosis and giardiasis, which highlighted the prominent role of long-term (>8 months) lags. Our study presents novel insights on the influence that extreme temperature and precipitation can have on parasitic disease transmission in real-world settings. Additionally, we present preliminary evidence that the standard lag periods that are typically used in epidemiological studies to assess the impacts of extreme weather on cryptosporidiosis and giardiasis may not be capturing the entire relevant period.
Extracellular Histones Promote Calcium Phosphate-Dependent Calcification in Mouse Vascular Smooth Muscle Cells
Authors: Hoshino Tomonori , Kharaghani Davood , Kohno Shohei
Published: September 2023

Vascular calcification, a major risk factor for cardiovascular events, is associated with a poor prognosis in chronic kidney disease (CKD) patients. This process is often associated with the transformation of vascular smooth muscle cells (VSMCs) into cells with osteoblast-like characteristics. Damage-associated molecular patterns (DAMPs), such as extracellular histones released from damaged or dying cells, are suspected to accumulate at calcification sites. To investigate the potential involvement of DAMPs in vascular calcification, we assessed the impact of externally added histones (extracellular histones) on calcium and inorganic phosphate-induced calcification in mouse VSMCs. Our study found that extracellular histones intensified calcification. We also observed that the histones decreased the expression of VSMC marker genes, while simultaneously increasing the expression of osteoblast marker genes. Additionally, histones treated with DNase I, which degrades dsDNA, attenuated this calcification, compared with the non-treated histones, suggesting a potential involvement of dsDNA in this process. Elevated levels of dsDNA were also detected in the serum of CKD model mice, underlining its potential role in vascular calcification in CKD. Our findings suggest that extracellular histones could play a pivotal role in the vascular calcification observed in CKD.

Graphical abstract
Pre-existing tissue mechanical hypertension at adherens junctions disrupts apoptotic extrusion in epithelia
Authors: Mann Zoya , Lim Fayth , Verma Suzie , Nanavati Bageshri N. , Davies Julie M. , Begun Jakob , Hardeman Edna C. , Gunning Peter W. , Subramanyam Deepa , Yap Alpha S. , Duszyc Kinga
Published: September 2023

Apical extrusion is a tissue-intrinsic process that allows epithelia to eliminate unfit or surplus cells. This is exemplified by the early extrusion of apoptotic cells, which is critical to maintain the epithelial barrier and prevent inflammation. Apoptotic extrusion is an active mechanical process, which involves mechanotransduction between apoptotic cells and their neighbours, as well as local changes in tissue mechanics. Here we report that the pre-existing mechanical tension at adherens junctions conditions the efficacy of apoptotic extrusion. Specifically, increasing baseline mechanical tension by overexpression of a phosphomimetic Myosin II regulatory light chain (MRLC) compromises apoptotic extrusion. This occurs when tension is increased in either the apoptotic cell or its surrounding epithelium. Further, we find that the pro-inflammatory cytokine, TNFα, stimulates Myosin II and increases baseline AJ tension to disrupt apical extrusion, causing apoptotic cells to be retained in monolayers. Importantly, reversal of mechanical tension with an inhibitory MRLC mutant or tropomyosin inhibitors is sufficient to restore apoptotic extrusion in TNFα-treated monolayers. Together, these findings demonstrate that baseline levels of tissue tension are important determinants of apoptotic extrusion, which can potentially be co-opted by pathogenetic factors to disrupt the homeostatic response of epithelia to apoptosis.
Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity
Authors: Bläsius Katharina , Ludwig Lena , Knapp Sarah , Flaßhove Charlotte , Sonnabend Friederike , Keller Diandra , Tacken Nikola , Gao Xintong , Kahveci-Türköz Selcan , Grannemann Caroline , Babendreyer Aaron , Adrain Colin , Huth Sebastian , Baron Jens Malte , Ludwig Andreas , Düsterhöft Stefan
Published: September 2023

The protease ADAM17 plays an important role in inflammation and cancer and is regulated by iRhom2. Mutations in the cytosolic N-terminus of human iRhom2 cause tylosis with oesophageal cancer (TOC). In mice, partial deletion of the N-terminus results in a curly hair phenotype (cub). These pathological consequences are consistent with our findings that iRhom2 is highly expressed in keratinocytes and in oesophageal cancer. Cub and TOC are associated with hyperactivation of ADAM17-dependent EGFR signalling. However, the underlying molecular mechanisms are not understood. We have identified a non-canonical, phosphorylation-independent 14-3-3 interaction site that encompasses all known TOC mutations. Disruption of this site dysregulates ADAM17 activity. The larger cub deletion also includes the TOC site and thus also dysregulated ADAM17 activity. The cub deletion, but not the TOC mutation, also causes severe reductions in stimulated shedding, binding, and stability of ADAM17, demonstrating the presence of additional regulatory sites in the N-terminus of iRhom2. Overall, this study contrasts the TOC and cub mutations, illustrates their different molecular consequences, and reveals important key functions of the iRhom2 N-terminus in regulating ADAM17.