bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolites mediate the causal associations between gut microbiota and NAFLD: a Mendelian randomization study
Authors: Ouyang Chen , Liu Pengpeng , Liu Yiwei , Lan Jianwei , Liu Quanyan
Published: July 2024

Background

Although gut microbiota and serum metabolite composition have been observed to be altered in patients with non-alcoholic fatty liver disease (NAFLD), previous observational studies have demonstrated inconsistent results. As this may be influenced by factors such as confounders and reverse causality, we used Mendelian randomization to clarify the causal effect of gut microbiota and blood metabolites on NAFLD.

Methods

In this research, we performed a two-step Mendelian randomization analysis by utilizing genome-wide association study (GWAS) data obtained from MiBioGen and UK Biobank. To mitigate potential errors, we employed False Discovery Rate (FDR) correction and linkage unbalanced regression (LDSC) analysis. Sensitivity analyses including cML-MA and bidirectional Mendelian randomization were performed to ensure the robustness of the results.

Results

In this study, a total of nine gut microbiota and seven metabolites were found to be significantly associated with NAFLD. MR analysis of the above findings revealed a causal relationship between Ruminococcus2 and cysteine-glutathione disulfide (OR = 1.17, 95%CI = 1.006–1.369, P = 0.041), as well as 3-indoleglyoxylic acid (OR = 1.18, 95%CI = 1.011–1.370, P = 0.036). For each incremental standard deviation in Ruminococcus2 abundance, there was a corresponding 26% reduction in NAFLD risk (OR = 0.74, 95%CI = 0.61–0.89, P = 0.0012), accompanied by a 17% increase in cysteine-glutathione disulfide levels (OR = 1.17, 95%CI = 1.01–1.37, P = 0.041) and an 18% increase in 3-indoleglyoxylic acid levels (OR = 1.18, 95%CI = 0.81-1.00, P = 0.036). The proportion mediated by cysteine-glutathione disulfide is 11.2%, while the proportion mediated by 3-indoleglyoxylic acid is 7.5%.

Conclusion

Our study suggests that increased abundance of specific gut microbiota may reduce the risk of developing NAFLD, and this relationship could potentially be mediated through blood metabolites.
Effects of neurofeedback training on the alpha activity in quantitative electroencephalography, cognitive function, and speech perception in elderly with presbycusis: a quasi-experimental study
Authors: Kim Hyoung Jae , Weon Hee Wook , Son Hae Kyoung
Published: July 2024

Background

This study aimed to investigate the effects of neurofeedback training (NFT) on alpha activity in quantitative electroencephalography (QEEG), cognitive function, and speech perception in elderly with presbycusis.

Methods

This study was conducted from June 15 to November 30, 2020. The experimental group (n = 28) underwent NFT, while the control group (n = 31) was instructed to continue with their routine daily life. The NFT conducted for 40 min, two times a week, for a total of 16 sessions and was performed using Neuroharmony S and BrainHealth 2.7. The alpha activity was measured as alpha waves using QEEG. The cognitive function was measured using the Korean version of Mini-Mental Status Examination, digit span forward and backward (DSF and DSB). The speech perception was measured using the word and sentence recognition score (WRS and SRS) using an audiometer with the Korean Standard Monosyllabic Word Lists for Adults.

Results

The experimental group demonstrated improvement in the alpha wave of the left frontal lobe measured as alpha activity (t=-2.521, p = .018); MMSE-K (t=-3.467, p < .01), and DSF (t=-2.646, p < .05) measured as cognitive function; and WRS (t=-3.255, p = .003), and SRS (t=-2.851, p = .008) measured as speech perception compared to the control group.

Conclusions

This study suggests that NFT could be considered an effective cognitive and auditory rehabilitation method based on brain and cognitive science for improving alpha activity, cognitive function, and speech perception.
Abnormal resting-state functional connectivity in subregions of amygdala in adults and adolescents with major depressive disorder
Authors: Guan Lin , Liu Rui , Wang Changshuo , Fan Qingchen , Zhou Jingjing , Wang Yun , Feng Yuan , Liu Jing , Zhou Yuan , Wang Gang , Chen Xu
Published: July 2024

Background

The different symptoms of major depressive disorder (MDD) in adolescents compared to adults suggested there may be differences in the pathophysiology between adolescents and adults with MDD. However, despite the amygdala being considered critical in the pathophysiology, there was limited knowledge about the commonalities and differences in the resting-state functional connectivity (rsFC) of amygdala subregions in MDD patients of different age groups.

Methods

In the current study, 65 adolescents (46 with MDD and 19 controls) and 91 adults (35 with MDD and 56 controls) were included. A seed-based functional connectivity analysis was performed for each of the amygdala subregions. A 2 × 2 ANOVA was used to analyze the main effect of age, diagnosis, and their interaction on the rsFC of each subregion.

Results

A significant main effect of age was revealed in the rsFC of bilateral centromedial (CM) subregions and right laterobasal (LB) subregion with several brain regions in the limbic system and frontoparietal network. The significant main effect of diagnosis showed MDD patients of different ages showed higher connectivity than controls between the right LB and left middle frontal gyrus (MFG).

Conclusions

The rsFC of specific amygdala subregions with brain regions in the limbic system and frontoparietal network is affected by age, indicating a distinct amygdala connectivity profile in adolescents. The decreased rsFC between the right LB and the left MFG in adolescents and adults with MDD could serve as a diagnostic biomarker and a target of nonpharmacological treatment for MDD.
Accuracy of renovo predictions on variants reclassified over time
Authors: Bonetti Emanuele , Tini Giulia , Mazzarella Luca
Published: July 2024

Background

Interpreting the clinical consequences of genetic variants is the central problem in modern clinical genomics, for both hereditary diseases and oncology. However, clinical validation lags behind the pace of discovery, leading to distressing uncertainty for patients, physicians and researchers. This “interpretation gap” changes over time as evidence accumulates, and variants initially deemed of uncertain (VUS) significance may be subsequently reclassified in pathogenic/benign. We previously developed RENOVO, a random forest-based tool able to predict variant pathogenicity based on publicly available information from GnomAD and dbNFSP, and tested on variants that have changed their classification status over time. Here, we comprehensively evaluated the accuracy of RENOVO predictions on variants that have been reclassified over the last four years.

Methods

we retrieved 16 retrospective instances of the ClinVar database, every 3 months since March 2020 to March 2024, and analyzed time trends of variant classifications. We identified variants that changed their status over time and compared RENOVO predictions generated in 2020 with the actual reclassifications.

Results

VUS have become the most represented class in ClinVar (44.97% vs. 9.75% (likely) pathogenic and 40,33% (likely) benign). The rate of VUS reclassification is linear and slow compared to the rate of VUS reporting, exponential and currently ~ 30x faster, creating a growing divide between what can be sequenced vs. what can be interpreted. Out of 10,196 VUS variants in January 2020 that have undergone a clinically meaningful reclassification to march 2024, RENOVO correctly classified 82.6% in 2020. In addition, RENOVO correctly identified the majority of the few variants that switched clinically meaningful classes (e.g., from benign to pathogenic and vice versa). We highlight variant classes and clinically relevant genes for which RENOVO provides particularly accurate estimates. In particularly, genes characterized by large prevalence of high- or low-impact variants (e.g., POLE, NOTCH1, FANCM etc.). Suboptimal RENOVO predictions mostly concern genes validated through dedicated consortia (e.g., BRCA1/2), in which RENOVO would anyway have a limited impact.

Conclusions

Time trend analysis demonstrates that the current model of variant interpretation cannot keep up with variant discovery. Machine learning-based tools like RENOVO confirm high accuracy that can aid in clinical practice and research.
Including the values of UK ethnic minority communities in policies to improve physical activity and healthy eating
Authors: Gafari Olatundun , Stokes Maria , Agyapong-Badu Sandra , Alwan Nisreen A. , Calder Philip C. , McDonough Suzanne , Tully Mark A. , Barker Mary
Published: July 2024

Physical activity and healthy eating are important for physical and mental health, yet long-standing inequalities constrain the ability of ethnic minorities in the United Kingdom (UK) to adopt these behaviours. Programmes aimed to improve these behaviours have also often not been engaged with by these communities. This study therefore aimed to: (1) identify the values underlying the physical activity and healthy eating behaviours of UK ethnic minorities and (2) explore how structural, socio-economic and environmental factors interact with these values to influence their physical activity and healthy eating behaviours. The study adopted a relativist ontological and subjectivist epistemological philosophical assumption. Qualitative interviews were used to address research objectives. A total of 10 group and five individual interviews were conducted with 41 participants. All participants were from an ethnic minority background (Black, Asian or Mixed according to the UK Office for National Statistics classification), recruited purposively and aged between 18 and 86 years and were living in England and Wales. Data were analysed using inductive thematic analysis. Community engagement was embedded throughout the study. We found that culture and family, community and social life, and health are important values underlying the physical activity and healthy eating behaviours of UK ethnic minority communities. External factors, including racism and access (geographical, social and economic), interact with these values to drive health behaviours. Using an illustrative guide, we conclude the paper with policy and practice recommendations on how public health programmes on physical activity and healthy eating can be aligned with these values to ensure relevance for ethnic minority communities.
Association between disease activity of rheumatoid arthritis and risk of complications following total hip arthroplasty: a retrospective cohort study
Authors: Lai Yahao , Tang Haiwei , Ding Zichuan , Huang Chao , Cai Yongrui , Luo Zeyu , Zhou Zongke
Published: July 2024

Background

Identifying rheumatoid arthritis patients at higher risk of complications after total hip arthroplasty could make perioperative management more effective. Here we examined whether disease activity is associated with risk of such complications.

Methods

We retrospectively analyzed data for 337 rheumatoid arthritis patients at our medical center who underwent primary total hip arthroplasty. Rheumatoid arthritis patients were categorized according to the simplified disease activity index (SDAI), the values of which at admission and follow-up were averaged together. Logistic regression was used to examine associations of mean SDAI with rates of dislocation, infection, periprosthetic fracture and aseptic loosening. As controls, 337 osteoarthritis patients who did not have systemic inflammation and who underwent the same procedure were matched across numerous clinicodemographic variables.

Results

Among the 337 rheumatoid arthritis patients, 38 (11.3%) had postoperative complications, the rates of which varied significantly from 0 to 17.5% (p = 0.003) among the four subgroups whose disease activity based on mean SDAI was categorized as high, moderate, low or in remission. Each 1-unit increase in mean SDAI was associated with a significant increase in risk of postoperative complications (OR 1.015, 95% CI 1.001–1.029, p = 0.035). Across all rheumatoid arthritis patients, rate of complications did not differ significantly between patients who received disease-modifying anti-rheumatic drugs or other treatments. Rates of dislocation, of infection or of all postoperative complications combined were significantly lower among osteoarthritis controls than among rheumatoid arthritis patients.

Conclusion

Greater mean SDAI is associated with higher risk of dislocation, infection and composite postoperative complications after total hip arthroplasty in rheumatoid arthritis patients. These patients show a significantly higher rate of postoperative complications than osteoarthritis patients, likely reflecting the influence of systemic inflammation. Disease activity should be reduced as much as possible in rheumatoid arthritis patients before they undergo total hip arthroplasty.
Short-term outcomes after surgical aortic valve replacement in elderly patients - results of a comparative cohort study
Authors: Wu Diana A. , Lang Peter , Varghese David , Al-Attar Nawwar , Shaikhrezai Kasra , Zamvar Vipin , Nair Sukumaran
Published: July 2024

Background

With the introduction of transcatheter aortic valve implantation, the role of surgical aortic valve replacement (SAVR) in elderly patients has been called into question. We investigated the short-term outcomes of SAVR in the elderly population.

Methods

All patients aged ≥ 70 years who underwent isolated SAVR in our centre between 2008 and 2017 were included in the study. Survival at 30 days and 1 year were compared for patients aged 70–79 years (n = 809) versus patients aged ≥ 80 years (n = 322). Factors associated with poorer survival outcomes were identified using multivariable Cox regression analysis.

Results

Patients aged 70–79 years and patients aged ≥ 80 years had similar survival rates at 30 days (98.1% vs. 98.4%, p = 0.732) and 1 year (96.0% vs. 94.1%, p = 0.162) post-SAVR. This remained true after multivariable adjustment. Risk factors for 30 day all-cause mortality included insulin dependent diabetes (HR 6.17, 95% CI 1.32–28.92, p = 0.021) and increasing cardiopulmonary bypass time (HR 2.72, 95% CI 1.89–3.91, p < 0.0001). Significant risk factors for 1 year all-cause mortality were New York Heart Association (NYHA) class IV (HR 6.25, 95% CI 1.55–25.24, p = 0.010) and longer cardiopulmonary bypass time (HR 1.94, 95% CI 1.40–2.69, p < 0.0001). Similar results were obtained for cardiac-specific mortality.

Conclusions

Short-term outcomes of SAVR are excellent in elderly patients and age alone is not a predictor of poorer outcomes. However, the increased risk of mortality in patients with insulin-dependent diabetes and those with severe functional impairment (NYHA class IV) should be carefully considered when selecting patients for SAVR in this elderly population.
Micrometastases in axillary lymph nodes in breast cancer, post-neoadjuvant systemic therapy
Authors: Lee Janghee , Park Seho , Bae Soong June , Ji Junghwan , Kim Dooreh , Kim Jee Ye , Park Hyung Seok , Ahn Sung Gwe , Kim Seung Il , Park Byeong-Woo , Jeong Joon
Published: July 2024

Introduction

The significance of minimal residual axillary disease, specifically micrometastases, following neoadjuvant systemic therapy (NST) remains largely unexplored. Our study aimed to elucidate the prognostic implications of micrometastases in axillary and sentinel lymph nodes following NST.

Methods

This retrospective study analyzed primary breast cancer patients who underwent surgery after NST from September 2006 through February 2018. All patients received axillary lymph node dissection (ALND), either with or without sentinel lymph node biopsy. Recurrence-free survival (RFS)-associated variables were identified using a multivariate Cox proportional hazard model.

Results

Of the 978 patients examined, 438 (44.8%) exhibited no pathologic lymph node involvement (ypN0) after NST, while 89 (9.1%) had micrometastases (ypN1mi) and 451 (46.7%) had macrometastases (ypN+). Notably, 51.1% of the patients with sentinel lymph node micrometastases (SLNmi) had additional metastases, nearly triple that of SLN-negative patients (P < 0.001), and 29.8% of SLNmi patients were upstaged with the ALND. Although ypN1mi was not associated with RFS in patients post-NST (HR, 1.02; 95% CI, 0.42–2.49; P = 0.958), SLNmi patients experienced significantly worse RFS compared to SLN-negative patients (hazard ratio [HR], 2.23; 95% confidence intervals [CI], 1.12–4.46; P = 0.023). Additional metastases in SLNmi were more prevalent in patients with larger residual breast disease greater than 20 mm, HR-positive/HER2-negative subtype, and low Ki-67 LI (< 14%).

Conclusions

SLNmi is a negative prognostic factor significantly associated with additional non-SLN metastases, while ypN1mi does not influence the prognosis compared to ypN0. Hence, additional ALND may be warranted to confirm axillary nodal status in patients with SLNmi.
The role of ribosomal DNA methylation in embryonic development, aging and diseases
Authors: Yang Fei , Guo Xutong , Bao Yiming , Li Rujiao
Published: July 2024

The ribosomal DNA (rDNA) constitutes a remarkably conserved DNA sequence within species, located in the area of the nucleolus, and responsible for coding three major types of rRNAs (18S, 5.8S and 28S). While historical investigations into rDNA focused on its structure and coding capabilities, recent research has turned to explore its functional roles in various biological processes. In this review, we summarize the main findings of rDNA methylation with embryonic development, aging and diseases in multiple species, including epigenetic alterations, related biological processes and potential applications of rDNA methylation. We present an overview of current related research and identify gaps in this field.
Structural relationship of the social-ecological factors and psychological factors on physical activity
Authors: Sabo Abdulwali , Kuan Garry , Kueh Yee Cheng
Published: July 2024

The present study examines the mediating effect of psychological factors in the structural relationships between social and physical environmental factors and the amount of physical activity among undergraduate students at Universiti Sains Malaysia. The sample consisted of 422 students with a mean age of 20.2 years (SD = 1.27). The majority of the students were female (69.7%) and Malay (81.3%). Standardized scales were used to measure the total amount of physical activity and all the study variables. The final SEM had a good fit to the data: CFI = 0.968, TLI = 0.948, SRMR = 0.036, RMSEA (90%CI) = 0.046 (0.025, 0.065), RMSEA p-value = 0.609 with 11 paths relationships. Family support had a significant effect on perceived benefits and perceived barriers. The effect of friend support on physical activity was significantly mediated by perceived benefits, self-efficacy, and psychological needs satisfaction. The effect of the availability of exercise facilities on physical activity was significantly mediated by perceived benefits and psychological needs satisfaction. Furthermore, psychological needs satisfaction mediated the effect of perceived benefits, perceived barriers, and self-efficacy on physical activity. The study findings illustrated that the application of the social-ecological model and psychological factors is important in order to understand and promote positive physical activity behaviour.
Movement behavior in a dominant ungulate underlies successful adjustment to a rapidly changing landscape following megafire
Authors: Calhoun Kendall L. , Connor Thomas , Gaynor Kaitlyn M. , Van Scoyoc Amy , McInturff Alex , Kreling Samantha E.S. , Brashares Justin S.
Published: July 2024

Background

Movement plays a key role in allowing animal species to adapt to sudden environmental shifts. Anthropogenic climate and land use change have accelerated the frequency of some of these extreme disturbances, including megafire. These megafires dramatically alter ecosystems and challenge the capacity of several species to adjust to a rapidly changing landscape. Ungulates and their movement behaviors play a central role in the ecosystem functions of fire-prone ecosystems around the world. Previous work has shown behavioral plasticity is an important mechanism underlying whether large ungulates are able to adjust to recent changes in their environments effectively. Ungulates may respond to the immediate effects of megafire by adjusting their movement and behavior, but how these responses persist or change over time following disturbance is poorly understood.

Methods

We examined how an ecologically dominant ungulate with strong site fidelity, Columbian black-tailed deer (Odocoileus hemionus columbianus), adjusted its movement and behavior in response to an altered landscape following a megafire. To do so, we collected GPS data from 21 individual female deer over the course of a year to compare changes in home range size over time and used resource selection functions (RSFs) and hidden Markov movement models (HMMs) to assess changes in behavior and habitat selection.

Results

We found compelling evidence of adaptive capacity across individual deer in response to megafire. Deer avoided exposed and severely burned areas that lack forage and could be riskier for predation immediately following megafire, but they later altered these behaviors to select areas that burned at higher severities, potentially to take advantage of enhanced forage.

Conclusions

These results suggest that despite their high site fidelity, deer can navigate altered landscapes to track rapid shifts in encounter risk with predators and resource availability. This successful adjustment of movement and behavior following extreme disturbance could help facilitate resilience at broader ecological scales.
Effects of MRI magnetic iron oxide nanoparticles on the structural and enzymatic properties of liver-related enzymes
Authors: Mirzajani Fateme , Rostamzadeh Azam , Tahmasian Zepiur , Obaid Heydar Sudan Abbas , Motevalli Seyed Mohammad
Published: July 2024

Cancer survivors undergo meticulous examinations, including regular magnetic resonance imaging (MRI) scans, to monitor the risk of disease recurrence. The use of magnetic iron nanoparticles (MNPs) enhances MRI accuracy. However, post-injection, MNPs exhibit a notable affinity for binding with proteins and biomolecules, forming a dynamic protein coating called a protein corona (CORONA). While there are reports of its elimination in the liver and kidney metabolism system, patients undergoing this method have shown symptoms of liver problems and related enzyme alterations. This study aims to discern whether the impact of MNPs on liver enzymes significantly contributes to liver damage. The investigation focuses on the effects of magnetic nanoparticles (MNPs) on selected enzymes, including alanine aminotransferase (ALT), aspartate transaminase (AST), α-amylase, and lipase. Employing 104 experiments over a central composite design (CCD), the study evaluates the effects of agents on MNP and enzyme structure, stability, and properties: enzyme assay, electron microscopy, and circular dichroism of secondary structure after interaction with MNPs. The study’s findings unveil the intricate relationship between MNPs and liver enzymes, providing valuable insights for clinical practices and refining the safety profile of MRI. This comprehensive exploration contributes to our understanding of potential implications and aids in optimizing the use of MNPs in medical imaging for cancer survivors.
Spatial co-occurrence of firearm homicides and opioid overdose deaths in Chicago by level of COVID-19 mortality, 2017–2021
Authors: McLone Suzanne G. , Pamplin II John R. , Pappu Jaii D. , Gradus Jaimie L. , Jay Jonathan S.
Published: July 2024

Background

Firearm homicide and opioid overdoses were already leading causes of death in the U.S. before both problems surged during the COVID-19 pandemic. Firearm violence, overdoses, and COVID-19 have all disproportionately harmed communities that are socially and economically marginalized, but the co-occurrence of these problems in the same communities has received little attention. To describe the co-occurrence of firearm homicides and opioid overdose deaths with COVID-19 mortality we used 2017–2021 medical examiner’s data from Chicago, IL. Deaths were assigned to zip codes based on decedents’ residence. We stratified zip codes into quartiles by COVID-19 mortality rate, then compared firearm homicide and fatal opioid overdose rates by COVID-19 quartile.

Findings

Throughout the study period, firearm homicide and opioid overdose rates were highest in the highest COVID-19 mortality quartile and lowest in the lowest COVID-19 mortality quartile. Increases in firearm homicide and opioid overdose were observed across all COVID-19 mortality quartiles.

Conclusions

High co-occurrence of these deaths at the community level call for addressing the systemic forces which made them most vulnerable before the pandemic. Such strategies should consider the environments where people reside, not only where fatal injuries occur.
High-resolution 3-D imaging of electron density perturbations using ultra-dense GNSS observation networks in Japan: an example of medium-scale traveling ionospheric disturbances
Authors: Fu Weizheng , Otsuka Yuichi , Ssessanga Nicholas
Published: July 2024

For the first time using computerized ionospheric tomography (CIT) and leveraging ultra-dense slant total electron content (STEC) measurements derived from two ground-based Global Navigation Satellite System (GNSS) receiver networks in Japan, we have reconstructed the 3-D field-aligned structure of nighttime medium-scale traveling ionospheric disturbances (MSTIDs) with high spatiotemporal resolution. The CIT algorithm focuses on electron density perturbation components, allowing for the imaging of disturbances with small amplitudes and scales. Slant TECs used for CIT are setup to consist of two components: the background derived from IRI-2016 model and TEC perturbations obtained by subtracting a 30-min running average from observations. The resolution is set to 0.25º in latitude and longitude, 10 km in altitude, 30 s in time. Simulations were conducted to assess the performance of the CIT algorithm, revealing that this technique has good fidelity by accurately reconstructing more than 80% of the electron density perturbations. The focus is on the nighttime event of July 4, 2022, when data were accessible. The reconstruction results show that the MSTIDs initially form at lower altitudes and subsequently develop to exhibit large amplitudes and scales that extend to higher altitudes, characterized by a well-defined frontal structure with electrodynamic signatures. These results are consistent with theories and snippets of observational evidence regarding electromagnetic-influenced MSTIDs, hence affirming the effectiveness of the developed CIT technique in probing of the variations in the 3-D structure of ionospheric electron density. This is expected to contribute to a compressive understanding of the underlying mechanisms of ionospheric inhomogeneities.

Graphical Abstract
The ADVanced Organ Support (ADVOS) hemodialysis system removes IL-6: an in vitro proof-of-concept study
Authors: Himmelein Susanne , Perez Ruiz de Garibay Aritz , Brandel Veronika , Zierfuß Frank , Bingold Tobias Michael
Published: July 2024

Background

IL-6 is a pleiotropic cytokine modulating inflammation and metabolic pathways. Its proinflammatory effect plays a significant role in organ failure pathogenesis, commonly elevated in systemic inflammatory conditions. Extracorporeal blood purification devices, such as the Advanced Organ Support (ADVOS) multi hemodialysis system, might offer potential in mitigating IL-6's detrimental effects, yet its efficacy remains unreported.

Methods

We conducted a proof-of-concept in vitro study to assess the ADVOS multi system's efficacy in eliminating IL-6. Varying concentrations of IL-6 were introduced into a swine blood model and treated with ADVOS multi for up to 12 h, employing different blood and concentrate flow rates. IL-6 reduction rate, clearance, and dynamics in blood and dialysate were analyzed.

Results

IL-6 clearance rates of 0.70 L/h and 0.42 L/h were observed in 4 and 12-h experiments, respectively. No significant differences were noted across different initial concentrations. Reduction rates ranged between 40 and 46% within the first 4 h, increasing up to 72% over 12 h, with minimal impact from flow rate variations. Our findings suggest that an IL-6-albumin interaction and convective filtration are implicated in in vitro IL-6 elimination with ADVOS multi.

Conclusions

This study demonstrates for the first time an efficient and continuous in vitro removal of IL-6 by ADVOS multi at low blood flow rates. Initial concentration-dependent removal transitions to more consistent elimination over time. Further clinical investigations are imperative for comprehensive data acquisition.
Shaping understandings through reflexive practice: Learnings from participatory research on aging with multiple sclerosis
Authors: Bergien Sofie Olsgaard , Skovgaard Lasse , Steenberg Josephine Lyngh , Kristiansen Maria
Published: July 2024

Background

Participatory research has gained traction as an approach to unlock perspectives when creating scientific knowledge and to facilitate societal changes. By conducting research with people, participatory research strives to engage individuals’ perspectives in designing, conducting, and disseminating the research. Nevertheless, few studies have unpacked how understandings of the studied phenomenon are shaped among diverse research partners and, concurrently, how different perspectives are combined. Nested within an overall participatory mixed methods study on aging with multiple sclerosis (MS), this qualitative study explores how understandings of aging with MS are shaped in encounters between university researchers, older adults with MS, and employees in a patient association.

Methods

The study was collaboratively conducted in Denmark by three research partners: a group of older adults with MS, employees in a patient association, and university researchers. Data on how different understandings of aging with MS were represented and shaped during the three-year research process was generated through field notes, meeting minutes, focus group interviews, and individual interviews. The collected data was analyzed through a thematic network analysis.

Results

The study demonstrates how different understandings of aging with MS were represented among the research partners when the research was initiated. These understandings were shaped prior to —and, therefore, outside—the research setting, drawing from the research participants’ lived experiences, professional backgrounds, and organizational cultures or situated in larger societal narratives. Through a process centered on reflexivity among the engaged research partners, the understandings of what it means to age with MS was shaped and re-shaped and eventually merged into a more dynamic understanding of later life with MS where different perspectives could co-exist.

Conclusion

The findings demonstrate that research partners, including older adults with MS and employees from a patient association, brought diverse understandings to the study. Reflexive practices enabled these perspectives to co-exist, enhancing engagement and transparency, and fostering a dynamic understanding of later life with MS. This highlights the value of reflexivity in evolving complex understandings within participatory research.
Oncostatin M-driven macrophage-fibroblast circuits as a drug target in autoimmune arthritis
Authors: Huynh Nam Cong-Nhat , Ling Rui , Komagamine Masatsugu , Shi Tianshu , Tsukasaki Masayuki , Matsuda Kotaro , Okamoto Kazuo , Asano Tatsuo , Muro Ryunosuke , Pluemsakunthai Warunee , Kollias George , Kaneko Yuko , Takeuchi Tsutomu , Tanaka Sakae , Komatsu Noriko , Takayanagi Hiroshi
Published: July 2024

Background

Recent single-cell RNA sequencing (scRNA-seq) analysis revealed the functional heterogeneity and pathogenic cell subsets in immune cells, synovial fibroblasts and bone cells in rheumatoid arthritis (RA). JAK inhibitors which ameliorate joint inflammation and bone destruction in RA, suppress the activation of various types of cells in vitro. However, the key cellular and molecular mechanisms underlying the potent clinical effects of JAK inhibitors on RA remain to be determined. Our aim is to identify a therapeutic target for JAK inhibitors in vivo.

Methods

We performed scRNA-seq analysis of the synovium of collagen-induced arthritis (CIA) mice treated with or without a JAK inhibitor, followed by a computational analysis to identify the drug target cells and signaling pathways. We utilized integrated human RA scRNA-seq datasets and genetically modified mice administered with the JAK inhibitor for the confirmation of our findings.

Results

scRNA-seq analysis revealed that oncostatin M (OSM) driven macrophage-fibroblast interaction is highly activated under arthritic conditions. OSM derived from macrophages, acts on OSM receptor (OSMR)-expressing synovial fibroblasts, activating both inflammatory and tissue-destructive subsets. Inflammatory synovial fibroblasts stimulate macrophages, mainly through IL-6, to exacerbate inflammation. Tissue-destructive synovial fibroblasts promote osteoclast differentiation by producing RANKL to accelerate bone destruction. scRNA-seq analysis also revealed that OSM-signaling in synovial fibroblasts is the main signaling pathway targeted by JAK inhibitors in vivo. Mice specifically lacking OSMR in synovial fibroblasts (Osmr∆Fibro) displayed ameliorated inflammation and joint destruction in arthritis. The JAK inhibitor was effective on the arthritis of the control mice while it had no effect on the arthritis of Osmr∆Fibro mice.

Conclusions

OSM functions as one of the key cytokines mediating pathogenic macrophage-fibroblast interaction. OSM-signaling in synovial fibroblasts is one of the main signaling pathways targeted by JAK inhibitors in vivo. The critical role of fibroblast-OSM signaling in autoimmune arthritis was shown by a combination of mice specifically deficient for OSMR in synovial fibroblasts and administration of the JAK inhibitor. Thus, the OSM-driven synovial macrophage-fibroblast circuit is proven to be a key driver of autoimmune arthritis, serving as a crucial drug target in vivo.
Decentralized finance: a comparative bibliometric analysis in the Scopus and WoS databases
Authors: Aydaner Gülcihan , Okuyan H. Aydın
Published: July 2024

DeFi blockchain technology, known as decentralized finance today, separates from the traditional financial ecosystem and ushers the new financial landscape onto digital platforms. In decentralized financial applications, all digital assets are safeguarded by blockchain technology. Thanks to this technology, investors can transfer their financial assets without being dependent on banking authorities. Despite the numerous advantages they bring, financial assets based on the decentralized finance ecosystem come with certain disadvantages. These assets are difficult to control, easily manipulated, and are at risk due to their vulnerability to cyberattacks. This study conducted bibliometric analyses on a total of 930 publications registered in the Web of Science (WoS) and Scopus databases using the VOSviewer program. In both databases, “all fields” were filtered and scanned with the keyword “decentralized finance.” According to the results, the Scopus database has much richer content compared to the WoS database. The most cited author in the Scopus database was Chen Y, while in the WoS database, it was Nakomoto S. There has been a significant increase in the number of publications in both databases since 2020. Additionally, it was detected that the most cited countries in both databases were the USA, China and England, respectively. It has been observed that computer science comes to the fore in the publication rankings. Decentralized finance is an interdisciplinary field of study. Therefore, many more qualified hybrid studies are needed. More studies are needed, especially examining investor behavior. The analyses presented in this article will enable researchers to grasp the bigger picture from a holistic perspective.
Lung ultrasound among Expert operator’S: ScOring and iNter-rater reliability analysis (LESSON study) a secondary COWS study analysis from ITALUS group
Authors: Boero Enrico , Gargani Luna , Schreiber Annia , Rovida Serena , Martinelli Giampaolo , Maggiore Salvatore Maurizio , Urso Felice , Camporesi Anna , Tullio Annarita , Lombardi Fiorella Anna , Cammarota Gianmaria , Biasucci Daniele Guerino , Bignami Elena Giovanna , Deana Cristian , Volpicelli Giovanni , Livigni Sergio , Vetrugno Luigi
Published: July 2024

Background

Lung ultrasonography (LUS) is a non-invasive imaging method used to diagnose and monitor conditions such as pulmonary edema, pneumonia, and pneumothorax. It is precious where other imaging techniques like CT scan or chest X-rays are of limited access, especially in low- and middle-income countries with reduced resources. Furthermore, LUS reduces radiation exposure and its related blood cancer adverse events, which is particularly relevant in children and young subjects. The score obtained with LUS allows semi-quantification of regional loss of aeration, and it can provide a valuable and reliable assessment of the severity of most respiratory diseases. However, inter-observer reliability of the score has never been systematically assessed. This study aims to assess experienced LUS operators’ agreement on a sample of video clips showing predefined findings.

Methods

Twenty-five anonymized video clips comprehensively depicting the different values of LUS score were shown to renowned LUS experts blinded to patients’ clinical data and the study’s aims using an online form. Clips were acquired from five different ultrasound machines. Fleiss-Cohen weighted kappa was used to evaluate experts’ agreement.

Results

Over a period of 3 months, 20 experienced operators completed the assessment. Most worked in the ICU (10), ED (6), HDU (2), cardiology ward (1), or obstetric/gynecology department (1). The proportional LUS score mean was 15.3 (SD 1.6). Inter-rater agreement varied: 6 clips had full agreement, 3 had 19 out of 20 raters agreeing, and 3 had 18 agreeing, while the remaining 13 had 17 or fewer people agreeing on the assigned score. Scores 0 and score 3 were more reproducible than scores 1 and 2. Fleiss’ Kappa for overall answers was 0.87 (95% CI 0.815–0.931, p < 0.001).

Conclusions

The inter-rater agreement between experienced LUS operators is very high, although not perfect. The strong agreement and the small variance enable us to say that a 20% tolerance around a measured value of a LUS score is a reliable estimate of the patient's true LUS score, resulting in reduced variability in score interpretation and greater confidence in its clinical use.
Analysis of clozapine prescribing in the over-65s: 5-year retrospective study
Authors: Barclay James , Tomar Rahul , Gale Tim
Published: July 2024

Aims and method

Patients prescribed clozapine are increasingly living into old age. However, there is a lack of studies to guide prescribing in this age group. We sought to identify all clozapine patients in Hertfordshire Partnership NHS Foundation Trust over a 5-year period and review side-effect burden and co-prescribing in all patients aged over 65 years.

Results

We identified 69 patients. The majority (61%) were stable in terms of mental state; 94% of cases had experienced a side-effect within the past year, with constipation occurring most commonly (65% of cases).

Clinical implications

Our findings reveal a significant side-effect burden, particularly in relation to constipation. Clozapine-induced gastrointestinal hypomotility (CIGH) can be fatal; however, increasing age has not been a recognised risk factor for constipation in clozapine patients to date. This raises questions about increasing risk to physical health as patients age and adds to concerns about the lack of monitoring for CIGH.
Gut Microbial Changes Associated With Obesity in Youth With Type 1 Diabetes
Authors: Ismail Heba M , Perera Dimuthu , Mandal Rabindra , DiMeglio Linda A , Evans-Molina Carmella , Hannon Tamara , Petrosino Joseph , Javornik Cregeen Sara , Schmidt Nathan W
Published: July 2024

Context

Obesity is prevalent in type 1 diabetes (T1D) and is problematic with higher risk for diabetes complications. It is unknown to what extent gut microbiome changes are associated with obesity and T1D.

Objective

This work aimed to describe the gut microbiome and microbial metabolite changes associated with obesity in T1D. We hypothesized statistically significant gut microbial and metabolite differences in lean T1D youth (body mass index [BMI]: 5%-<85%) vs those with obesity (BMI: ≥95%).

Methods

We analyzed stool samples for gut microbial (using metagenomic shotgun sequencing) and short-chain fatty acid (SCFA) differences in lean (n = 27) and obese (n = 21) T1D youth in a pilot study. The mean ± SD age was 15.3 ± 2.2 years, glycated hemoglobin A1c 7.8 ± 1.3%, diabetes duration 5.1 ± 4.4 years, 42.0% female, and 94.0% were White.

Results

Bacterial community composition showed between sample diversity differences (β-diversity) by BMI group (P = .013). There was a higher ratio of Prevotella to Bacteroides in the obese group (P = .0058). There was a differential distribution of significantly abundant taxa in either the lean or obese groups, including increased relative abundance of Prevotella copri, among other taxa in the obese group. Functional profiling showed an upregulation of branched-chain amino acid (BCAA) biosynthesis in the obese group and upregulation of BCAA degradation, tyrosine metabolism, and secondary bile acid biosynthesis in the lean group. Stool SCFAs were higher in the obese vs the lean group (P < .05 for all).

Conclusion

Our findings identify a gut microbiome and microbial metabolite signature associated with obesity in T1D. These findings could help identify gut microbiome–targeted therapies to manage obesity in T1D.
Retinoic acid signalling regulates branchiomeric neck muscle development at the head/trunk interface
Authors: Dumas Camille E. , Rousset Célia , De Bono Christopher , Cortés Claudio , Jullian Estelle , Lescroart Fabienne , Zaffran Stéphane , Adachi Noritaka , Kelly Robert G.
Published: July 2024

Skeletal muscles of the head and trunk originate in distinct lineages with divergent regulatory programmes converging on activation of myogenic determination factors. Branchiomeric head and neck muscles share a common origin with cardiac progenitor cells in cardiopharyngeal mesoderm (CPM). The retinoic acid (RA) signalling pathway is required during a defined early time window for normal deployment of cells from posterior CPM to the heart. Here, we show that blocking RA signalling in the early mouse embryo also results in selective loss of the trapezius neck muscle, without affecting other skeletal muscles. RA signalling is required for robust expression of myogenic determination factors in posterior CPM and subsequent expansion of the trapezius primordium. Lineage-specific activation of a dominant-negative RA receptor reveals that trapezius development is not regulated by direct RA signalling to myogenic progenitor cells in CPM, or through neural crest cells, but indirectly through the somitic lineage, closely apposed with posterior CPM in the early embryo. These findings suggest that trapezius development is dependent on precise spatiotemporal interactions between cranial and somitic mesoderm at the head/trunk interface.
A Characterization of the Cardiac Physiology and Aortic Pulse Wave Properties of Artistic Swimmers Across Competitive Levels
Authors: BAKER RYLEIGH E. , CHEUNG CHRISTIAN P. , COATES ALEXANDRA M. , CURRIE KATHARINE D. , KING TREVOR J. , MOUNTJOY MARGO L. , BURR JAMIE F.
Published: July 2024

Purpose

The distinct physical and environmental stressors of artistic swimming (previously termed synchronized swimming) result in unique hemodynamic stimuli. Given that the hemodynamic stress associated with participation in an exercise modality drives adaptation of the heart and central vasculature, artistic swimming may produce a distinct cardiovascular phenotype. Presumably, athletes competing at the highest levels also have greater training exposure and thus exhibit more adaptation. The purpose of this study was to characterize cardiovascular form and function across the competitive spectrum of artistic swimmers.

Methods

Cardiovascular structure and function were compared in a cross-sectional study of healthy controls, varsity, and elite artistic swimmers, using pulse wave analysis, pulse wave velocity, and echocardiographic images both at rest and during isometric handgrip exercise.

Results

Aortic stiffness was similar across all groups, as were characteristics of the decomposed aortic pressure waveform. At rest, both varsity and elite swimmers demonstrated similar systolic function compared with controls. However, peak left ventricular twist was greater in varsity and elites (controls: 8.0 ± 3.9, varsity: 12.8 ± 8.6, elites: 13.4 ± 3.9; both P < 0.02). Furthermore, elites demonstrated greater peak left ventricular radial strain (controls: 29.2 ± 9.9, varsity: 32.5 ± 10.3, elites: 53.9 ± 15.1; both P < 0.001) and longitudinal strain (controls: −16.9 ± 1.6, varsity: −16.5 ± 1.8, elites: −19.5 ± 3.2; both P < 0.04). In contrast to controls, both varsity and elite artistic swimmers demonstrated no change in peak late diastolic transmitral filling velocity (controls: Δ0.2 ± 0.04 m·s−1, varsity: Δ0.06 ± 0.04 m·s−1, elites: Δ0.05 ± 0.04 m·s−1) during isometric handgrip exercise (both P > 0.05), with elites demonstrating lower peak velocity than varsity swimmers (P = 0.048), indicating preservation of diastolic function.

Conclusions

Artistic swimmers demonstrate distinct cardiac physiology at rest and during isometric handgrip, with a greater extent of distinguishing features observed in those competing at the highest level of competition.
The Impact of Legal Abortion on Maternal Mortality
Authors: Farin Sherajum Monira , Hoehn-Velasco Lauren , Pesko Michael F.
Published: July 2024

Legal abortion has recently been suggested as an essential health care service. In this study, we consider whether abortion legalization over 1969–1973 improved women’s health as measured by maternal mortality. Our event study results indicate that legal abortion substantially lowered non-White maternal mortality by 30–50 percent, with 134 non-White maternal deaths averted nationally in the first year abortion became legal. We also find that early state-level legalizations were crucial and more influential than the Roe v. Wade decision itself. (JEL I12, I18, J13, J16, K10, K38)