bluuebunny/crossref_metadata_2025 huggingface dataset:
Causal association between obesity and hypothyroidism: a two-sample bidirectional Mendelian randomization study
Authors: Qiu Yingkun , Liu Qinyu , Luo Yinghua , Chen Jiadi , Zheng Qingzhu , Xie Yuping , Cao Yingping
Published: January 2024

Introduction

Previous observational studies have reported a positive correlation between obesity and susceptibility to hypothyroidism; however, there is limited evidence from alternative methodologies to establish a causal link.

Methods

We investigated the causal relationship between obesity and hypothyroidism using a two-sample bidirectional Mendelian randomization (MR) analysis. Single-nucleotide polymorphisms (SNPs) associated with obesity-related traits were extracted from a published genome-wide association study (GWAS) of European individuals. Summarized diagnostic data of hypothyroidism were obtained from the UK Biobank. Primary analyses were conducted using the inverse variance-weighted (IVW) method with a random-effects model as well as three complementary approaches. Sensitivity analyses were performed to ascertain the correlation between obesity and hypothyroidism.

Results

MR analyses of the IVW method and the analyses of hypothyroidism/myxedema indicated that body mass index (BMI) and waist circumference (WC) were significantly associated with higher odds and risk of hypothyroidism. Reverse MR analysis demonstrated that a genetic predisposition to hypothyroidism was associated with an increased risk of elevated BMI and WC, which was not observed between WC adjusted for BMI (WCadjBMI) and hypothyroidism.

Discussion

Our current study indicates that obesity is a risk factor for hypothyroidism, suggesting that individuals with higher BMI/WC have an increased risk of developing hypothyroidism and indicating the importance of weight loss in reducing the risk of hypothyroidism.
Efficacy and safety of adjuvant radiation therapy in localized adrenocortical carcinoma
Authors: Wu Luming , Chen Jiayi , Su Tingwei , Jiang Lei , Han Yimin , Zhang Cui , Zhou Weiwei , Jiang Yiran , Zhong Xu , Wang Weiqing
Published: January 2024

Context

Adrenocortical carcinoma (ACC) is rare and have high rates of recurrence and mortality. The role of adjuvant radiation therapy (RT) in localized ACC was controversial.

Methods

We conducted a retrospective study in our center between 2015 and 2021 to evaluate the efficacy and safety of adjuvant RT in localized ACC. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to estimate the independent risk factors. Adverse events associated with RT were documented according to the toxicity criteria of the radiation therapy oncology group (RTOG) and the common terminology criteria for adverse events (CTCAE v5.0).

Results

Of 105 patients with localized ACC, 46 (43.8%) received adjuvant RT after surgery. The median radiation dose was 45.0Gy (range:30.0-50.4) and median follow up time was 36.5 (IQR: 19.7-51.8) months. In comparison to the no adjuvant RT group, patients with adjuvant RT had better 3-year OS (87.9% vs 79.5%, P=0.039), especially for patients with ENSAT I/II stage (P=0.004). Adjuvant RT also improved the median DFS time from 16.5months (95%CI, 12.0-20.9) to 34.6months (95%CI, 16.1-53.0). Toxicity of RT was generally mild and moderate with six grade 3 events.

Conclusions

Postoperative adjuvant RT significantly improved OS and DFS compared with the use of surgery alone in resected ACC patients. Although this retrospective study on RT in localized ACC indicates that RT is effective in ACC, its findings need to be prospectively confirmed.
Potential causal association between aspirin use and erectile dysfunction in European population: a Mendelian randomization study
Authors: Li Rongkang , Peng Lei , Deng Dashi , Li Guangzhi , Wu Song
Published: January 2024

Background

Aspirin, as one of the most commonly used drugs, possesses a broad spectrum of therapeutic applications. Presently, the potential association between aspirin usage and the risk elevation of erectile dysfunction (ED) remains inconclusive. The objective of this study employing two-sample Mendelian randomization (MR) was to clarify the causal impact of aspirin use on the risk of ED.

Methods

This study incorporated two sets of Genome-Wide Association Study (GWAS) summary statistics, one for aspirin use (46,946 cases and 286,635 controls) and another for ED (6,175 cases and 217,630 controls) in individuals of European ancestry. The inverse-variance weighted (IVW) method was employed as the primary approach, supplemented by MR-Egger, weighted median, weighted mode, and simple mode to estimate the causal effect of aspirin usage on the risk of ED development. To assess pleiotropy, the MR-PRESSO global test and MR-Egger regression were used. Cochran’s Q test was adopted to check heterogeneity, and the leave-one-out analysis was performed to confirm the robustness and reliability of the results.

Results

The causal association between genetically inferred aspirin use and ED was found by using inverse variance weighted (OR = 20.896, 95% confidence interval = 2.077-2.102E+2, P = 0.010). The sensitivity analysis showed that no pleiotropy and heterogeneity was observed. Furthermore, the leave-one-out analysis demonstrated that the findings were not significantly affected by any instrumental variables.

Conclusion

The results of this study highlighted the significance of aspirin use as a predisposing factor for ED and provided further evidence supporting the causal association between aspirin utilization and ED within European populations.
Immunometabolism, extracellular vesicles and cardiac injury
Authors: Omoto Ana C. M. , do Carmo Jussara M. , da Silva Alexandre A. , Hall John E. , Mouton Alan J.
Published: January 2024

Recent evidence from our lab and others suggests that metabolic reprogramming of immune cells drives changes in immune cell phenotypes along the inflammatory-to-reparative spectrum and plays a critical role in mediating the inflammatory responses to cardiac injury (e.g. hypertension, myocardial infarction). However, the factors that drive metabolic reprogramming in immune cells are not fully understood. Extracellular vesicles (EVs) are recognized for their ability to transfer cargo such as microRNAs from remote sites to influence cardiac remodeling. Furthermore, conditions such as obesity and metabolic syndrome, which are implicated in the majority of cardiovascular disease (CVD) cases, can skew production of EVs toward pro-inflammatory phenotypes. In this mini-review, we discuss the mechanisms by which EVs may influence immune cell metabolism during cardiac injury and factors associated with obesity and the metabolic syndrome that can disrupt normal EV function. We also discuss potential sources of cardio-protective and anti-inflammatory EVs, such as brown adipose tissue. Finally, we discuss implications for future therapeutics.
Discriminating early-stage diabetic retinopathy with subjective and objective perimetry
Authors: Sabeti Faran , van Kleef Joshua P. , Iyer Rakesh M. , Carle Corinne F. , Nolan Christopher J. , Chia Rong Hui , Maddess Ted
Published: January 2024

Introduction

To prevent progression of early-stage diabetic retinopathy, we need functional tests that can distinguish multiple levels of neural damage before classical vasculopathy. To that end, we compared multifocal pupillographic objective perimetry (mfPOP), and two types of subjective automated perimetry (SAP), in persons with type 2 diabetes (PwT2D) with either no retinopathy (noDR) or mild to-moderate non-proliferative retinopathy (mmDR).

Methods

Both eyes were assessed by two mfPOP test methods that present stimuli within either the central ±15° (OFA15) or ±30° (OFA30), each producing per-region sensitivities and response delays. The SAP tests were 24-2 Short Wavelength Automated Perimetry and 24-2 Matrix perimetry.

Results

Five of eight mfPOP global indices were significantly different between noDR and mmDR eyes, but none of the equivalent measures differed for SAP. Per-region mfPOP identified significant hypersensitivity and longer delays in the peripheral visual field, verifying earlier findings. Diagnostic power for discrimination of noDR vs. mmDR, and normal controls vs. PwT2D, was much higher for mfPOP than SAP. The mfPOP per-region delays provided the best discrimination. The presence of localized rather than global changes in delay ruled out iris neuropathy as a major factor.

Discussion

mfPOP response delays may provide new surrogate endpoints for studies of interventions for early-stage diabetic eye damage.
Adrenal incidentalomas, cortisol secretion and cancer: is there a real crosstalk?
Authors: Herrera-Martínez Aura D. , Román Ángel Rebollo , Corrales Eider Pascual , Idrobo Cindy , Ramírez Paola Parra , Rojas Patricia Martín , Lázaro Cristina Robles , Araujo-Castro Marta
Published: January 2024

Background

Cortisol has immunomodulatory effects that increase the risk and evolution of several diseases. Cancer is characterized by a proinflammatory state in which cells exert impaired function and proliferation. The relation between cortisol secretion and increased risk of malignant neoplasm, or their behavior, has not been fully elucidated.

Aim

To determine the relation between cortisol secretion and the prevalence and clinical outcome of malignant neoplasms in patients with adrenal incidentalomas (AIs).

Methods

Multicenter retrospective study that included 935 patients with AIs. Cortisol secretion was defined by a cortisol post-dexamethasone suppression test > 1.8 µg/dL, and nonfunctioning AIs (NFAIs) as a value ≤ 1.8 µg/dL.

Results

Cortisol secretion was evident in 30.8% of the patients and cancer in 23.6% (especially breast, colorectal, prostate and thyroid cancer). No differences in the cancer prevalence were found between patients with cortisol secretion and NFAIs (63.6% vs. 63.4%, p=0.10). After adjusting by age, cortisol secretion was not associated with the presence of cancer (OR 1.29, CI 0.93–1.78). However, cortisol secretion was significantly associated with stage IV of cancer at diagnosis (OR 2.68, CI 1.19– 6.00) and mortality (OR 3.2, CI 1.28- 7.97). Patients with NFAI and breast cancer required treatment with chemo- and radio-therapy more frequently that patients with cortisol secreting AI (90% vs 10% and 92.9% vs 7.1% respectively, p<0.05), similarly patients with prostate cancer required radiotherapy more frequently (90.9% vs 9.1%, p=0.05); also, patients with colorectal cancer and NFAI, tended to require chemotherapy more frequently(76.5% vs 23.5%, p=0.06).

Conclusion

Cortisol secretion does not increase the risk of malignant neoplasm, but it affects its clinical course, treatment requirements and mortality, leading to a worst prognosis and higher mortality when compared with patients with NFAIs.
A robust investment decision to deploy bioenergy carbon capture and storage—exploring the case of Stockholm Exergi
Authors: Stenström Oscar , Khatiwada Dilip , Levihn Fabian , Usher Will , Rydén Magnus
Published: January 2024

The upscaling of novel carbon dioxide removal, such as bioenergy carbon capture and storage (BECCS), to gigatonne scales is an urgent priority if global warming is to be limited to well below 2 °C. But political, economic, social, technological, environmental and regulatory uncertainty permeates BECCS projects and deters investors. To address this, we explore options to improve the robustness of BECCS deployment strategies in the face of multi-dimensional uncertainties. We apply Dynamic Adaptive Planning (DAP) through expert interviews and Robust Decision Making (RDM) through exploratory modelling, two decision making under deep uncertainty methods, to the case of Stockholm Exergi, an early mover aiming to deploy BECCS at a combined heat and power plant in the capital of Sweden. The main contributions of the research are to 1) illustrate how a quantification of robustness against uncertainty can support an investment decision to deploy BECCS 2) comprehensively cover uncertain vulnerabilities and opportunities of deploying BECCS, and 3) identify critical scenarios and adaptations to manage these uncertainties. The main conclusions are: investing in BECCS is relatively robust if assessing performance across many scenarios and if comparing the worst-cases of either investing, or not doing so. Not investing could miss out on up to € 3.8 billion in terms of net present value. The critical uncertainties of BECCS can be managed by strengthening biomass sustainability strategies and by gaining support for negative emission trading regulation on carbon markets, e.g., voluntary or Paris Agreement Article 6. Even in vulnerable scenarios of average electricity prices above 82 €/MWh, if trading regulation is implemented before 2030 and if negative emission prices exceed 151 €/CO2, investing in BECCS performs better than not doing so in 96% of cases. We suggest that facility-level parameters and cost-reductions are of little importance for BECCS investments and upscaling. It is regulatory certainty of operating revenues, e.g., through negative emission markets, that needs to be provided by policymakers.
Proposed multi-signal input fault diagnosis of wind turbine bearing based on glow model
Authors: Wang Bin , Wang Fei , Zou Yunbo , Fang Shunshun , Luan Hanzhang , Zhang Liang
Published: January 2024

In the fault diagnosis, the problem of insufficient fault samples and unbalanced number of fault category samples can occur. In this paper, we used Glow model to supplement the number of wind turbine bearing fault samples to enhance the diagnosis accuracy when fault samples are insufficient and the number of fault category samples is unbalanced. Meanwhile, we established a multi-input fault diagnosis model to achieve multi-location and multi-category fault diagnosis, and constructed some experimental under different scenarios. We took into account the noise interference in the actual operation and conducted comparison experiments under different scenarios, and the experimental results verified the new algorithm had good fault diagnosis effect.
Characteristics of nitrogen and phosphorus contents in soil and water in an agricultural catchment of the three Gorges reservoir area
Authors: Chen Chenglong , Deng Hua , Xin Guixin , Zhou Youwen
Published: January 2024

To explore the impact of different land use modes on the contents of nitrogen and phosphorus in soil and water in the agricultural basin of the Three Gorges Reservoir, the differences in the nitrogen and phosphorus contents in soil and shallow groundwater under different land use modes were studied by using sample data collected in the field. The typical agricultural small watershed at the heart of the reservoir area was selected as the research object. The differences in the nitrogen and phosphorus loss concentrations during the rainfall process and in the daily surface runoff of the two subcatchments with different land use compositions and spatial layouts were compared. The results show that under the five land use modes, the average total nitrogen (TN) content of the paddy soil (1.51 g/kg) was the highest and was significantly higher than that of the other four land use modes (p < 0.05); the average nitrate nitrogen (NO3−-N) content of the terraced soil in dry land (30.05 mg/kg) was the highest, and the dispersion degree was the greatest; and the total phosphorus (TP) content of the three types of sloping farmland was higher than that of terraced farmland, among which the total phosphorus content of the dryland sloping farmland (1.37 g/kg) was the highest and was significantly greater than that of the other types (p < 0.05); moreover, the available phosphorus (AP) content in the soil of the closely planted mulberry garden was the highest, with an average of 36.85 mg/kg. Under the different land use modes, the concentrations of TN and NO3−-N in the shallow groundwater varied greatly, while there were no obvious differences in the TP concentrations. Influenced by fertilization, the concentrations of TN and NO3−-N in the shallow groundwater clearly increased after fertilization in spring and autumn. The concentration of TP increased slightly, and the concentration was the highest when the rainfall was concentrated in summer. A comparison of the two subcatchments revealed that the interplanted mulberry and paddy fields at the bottom of the basin effectively reduced TN and TP outputs of surface runoff in the subcatchment.
Invasive behaviour of oak lace bug in forest ecosystems: a comparative analysis between thermophilous and mesophilous oak forests
Authors: Bălăcenoiu Flavius , Nețoiu Constantin , Toma Dragoș , Petrițan Ion Cătălin
Published: January 2024

Forest ecosystems provide invaluable ecological, economic, and social benefits, making them essential for global well-being. However, these ecosystems face various threats, including biological invasions by alien species. Among these, the oak lace bug (OLB), an invasive North American insect, has rapidly spread in Europe, impacting oak forests and raising concerns about its adaptation to new environments. OLB feeds on the undersides of oak leaves, extracting sap and causing chlorotic discoloration. Severe infestations lead to premature defoliation, increased susceptibility to diseases or pests and can also result in a substantial reduction in photosynthesis activity. This study aims to analyse OLB’s invasive behaviour in Romanian forest ecosystems, with a specific focus on the differences between thermophilous and mesophilous oak forests. The analysis covers 6 years of data and reveals critical insights. In the initial 4 years, OLB predominantly inhabited the extracarpathian regions of Romania, with concentrated presence in the southern, western, and northwestern areas. Forest ecosystems mainly affected between 2017 and 2020 were characterized by thermophilous oak forests in southern and western regions. However, in the last 2 years (2021–2022), OLB presence increased, particularly in lowland ecosystems, albeit with reduced damage intensity. The analysis also unveiled an adaptation and expansion of OLB in mesophilous forest ecosystems. Climatic factors, specifically temperature and precipitation, significantly influenced OLB’s behaviour, points with severe attacks exhibiting specific climatic conditions. In summary, this study provides crucial insights into OLB’s behaviour, emphasizing the role of climatic and environmental factors in its invasive tendencies.
Quantifying the contributions of climatic and human factors to vegetation net primary productivity dynamics in East Africa
Authors: Xu Minghui , Zhang Zhenke , Wang Yue , Liu Binglin
Published: January 2024

As an important part of the terrestrial ecosystem, vegetation dynamics are subject to impacts from both climate change and human activities. Clarifying the driving mechanisms of vegetation variation is of great significance for regional ecological protection and achieving sustainable development goals. Here, net primary productivity (NPP) was used to investigate the spatiotemporal variability of vegetation dynamics from 2000 to 2020 in East Africa, and its correlations with climate factors. Furthermore, we utilized partial derivatives analysis and set up different scenarios to distinguish the relative contributions of climatic and human factors to NPP changes. The results revealed that NPP exhibited a significant increase with 4.16 g C/m2/a from 2000 to 2020 in East Africa, and an upward trend was detected across 71.06% of the study area. The average contributions of precipitation, temperature, and solar radiation to the NPP inter-annual variations in East Africa were 2.02, −1.09, and 0.31 gC⋅m–2⋅a–1, respectively. Precipitation made the greatest positive contribution among all of the climatic factors, while temperature made strong negative contributions. The contributions of climate change and human activities to NPP changes were 1.24 and 2.34 gC⋅m–2⋅a–1, respectively. Moreover, the contribution rate of human activities to NPP increase was larger than that of climate change, while the role of climate change in NPP decrease was larger than that of human activities. The findings of the study can provide new evidence for a deeper understanding of ecosystem stability and carbon cycling in East Africa, as well as a reference for decision-making and scientific support for ecological environmental protection.
Genetic causality and site-specific relationship between sarcopenia and osteoarthritis: a bidirectional Mendelian randomization study
Authors: Jia Xue-Min , Deng Ting-Ting , Su Hang , Shi Hao-Jun , Qin Hao , Yu Gong-Chang , Yin Ying , Liu Fan-Jie , Shi Bin
Published: January 2024

Background: Previous studies demonstrated a controversial relationship between sarcopenia (SP) and osteoarthritis (OA) and their genetic causality is unclear. Thus, we conducted a Mendelian randomization (MR) analysis to evaluate the possible causal association between sarcopenia-related traits (appendicular lean mass (ALM), grip strength, usual walking pace) and OA.

Method: We used pooled genetic data from the UK Biobank for ALM(n = 450,243), left-hand grip strength (n = 461,026), right-hand grip strength (n = 461,089) and usual walking pace (n = 459,915). Moreover, summary statistics for OA were obtained from the latest study conducted by the Genetics of Osteoarthritis Consortium, including all OA (n = 826,690), hand OA (n = 303,7782), hip OA (n = 353,388) and knee OA (n = 396,054). The primary method for estimating causal effects was the inverse-variance weighted (IVW) method, with the utilizing of false discovery rate adjusted p values (PFDR). Additional MR methods such as MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median were employed as supplementary analyses.

Results: We discovered ALM (odds ratio (OR) = 1.103, 95% confidence interval (CI) = 1.052–1.156, PFDR = 2.87E-04), hand grip strength (left, IVW OR = 0.823, 95% CI = 0.712 to 0.952, PFDR = 0.020; right, OR = 0.826, 95% CI = 0.718 to 0.950, PFDR = 0.020), and usual walking pace (OR = 0.339, 95% CI = 0.204 to 0.564, PFDR = 2.38E-04) were causally associated with OA risk. In the reverse MR analysis, we identified a causal effect of OA on ALM (β = −0.258, 95% CI = −0.369 to 0.146, PFDR = 0.6.07E-06), grip strength (left, β = −0.064, 95% CI = −0.104 to 0.024, PFDR = 0.002; right, β = −0.055, 95% CI = −0.095 to 0.014, PFDR = 0.008), and usual walking pace (β = −0.104, 95% CI = −0.147 to 0.061, PFDR = 1.61E-05).

Conclusion: This present study suggests an obvious causality of SP on OA, with condition exhibiting site-specific effects, while evidence was also provided for the causal effect of OA on SP.
Treg in inborn errors of immunity: gaps, knowns and future perspectives
Authors: Kennedy-Batalla Rebeca , Acevedo Daniel , Luo Yiyi , Esteve-Solé Ana , Vlagea Alexandru , Correa-Rocha Rafael , Seoane-Reula Ma Elena , Alsina Laia
Published: January 2024

Regulatory T cells (Treg) are essential for immune balance, preventing overreactive responses and autoimmunity. Although traditionally characterized as CD4+CD25+CD127lowFoxP3hi, recent research has revealed diverse Treg subsets such as Tr1, Tr1-like, and CD8 Treg. Treg dysfunction leads to severe autoimmune diseases and immune-mediated inflammatory disorders. Inborn errors of immunity (IEI) are a group of disorders that affect correct functioning of the immune system. IEI include Tregopathies caused by genetic mutations affecting Treg development or function. In addition, Treg dysfunction is also observed in other IEIs, whose underlying mechanisms are largely unknown, thus requiring further research. This review provides a comprehensive overview and discussion of Treg in IEI focused on: A) advances and controversies in the evaluation of Treg extended subphenotypes and function; B) current knowledge and gaps in Treg disturbances in Tregopathies and other IEI including Treg subpopulation changes, genotype-phenotype correlation, Treg changes with disease activity, and available therapies, and C) the potential of Treg cell-based therapies for IEI with immune dysregulation. The aim is to improve both the diagnostic and the therapeutic approaches to IEI when there is involvement of Treg. We performed a non-systematic targeted literature review with a knowledgeable selection of current, high-quality original and review articles on Treg and IEI available since 2003 (with 58% of the articles within the last 6 years) in the PubMed database.
Pharmacogenomics of intravenous immunoglobulin response in Kawasaki disease
Authors: Shrestha Sadeep , Wiener Howard W. , Kajimoto Hidemi , Srinivasasainagendra Vinodh , Ledee Dolena , Chowdhury Sabrina , Cui Jinhong , Chen Jake Y. , Beckley Mikayla A , Padilla Luz A. , Dahdah Nagib , Tiwari Hemant K. , Portman Michael A.
Published: January 2024

Introduction

Kawasaki disease (KD) is a diffuse vasculitis in children. Response to high dose intravenous gamma globulin (IVIG), the primary treatment, varies according to genetic background. We sought to identify genetic loci, which associate with treatment response using whole genome sequencing (WGS).

Method

We performed WGS in 472 KD patients with 305 IVIG responders and 167 non-responders defined by AHA clinical criteria. We conducted logistic regression models to test additive genetic effect in the entire cohort and in four subgroups defined by ancestry information markers (Whites, African Americans, Asians, and Hispanics). We performed functional mapping and annotation using FUMA to examine genetic variants that are potentially involved IVIG non-response. Further, we conducted SNP-set [Sequence] Kernel Association Test (SKAT) for all rare and common variants.

Results

Of the 43,288,336 SNPs (23,660,970 in intergenic regions, 16,764,594 in introns and 556,814 in the exons) identified, the top ten hits associated with IVIG non-response were in FANK1, MAP2K3:KCNJ12, CA10, FRG1DP, CWH43 regions. When analyzed separately in ancestry-based racial subgroups, SNPs in several novel genes were associated. A total of 23 possible causal genes were pinpointed by positional and chromatin mapping. SKAT analysis demonstrated association in the entire MANIA2, EDN1, SFMBT2, and PPP2R5E genes and segments of CSMD2, LINC01317, HIVEPI, HSP90AB1, and TTLL11 genes

Conclusions

This WGS study identified multiple predominantly novel understudied genes associated with IVIG response. These data can serve to inform regarding pathogenesis of KD, as well as lay ground work for developing treatment response predictors.
Association between dietary antioxidant levels and chronic obstructive pulmonary disease: a mediation analysis of inflammatory factors
Authors: Liu Ziyi , Li Jiyuan , Chen Tuotuo , Zhao Xue , Chen Qing , Xiao Lihua , Peng Zhenyu , Zhang Hongliang
Published: January 2024

Introduction

The development of chronic obstructive pulmonary disease (COPD) is strongly associated with oxidative stress, but it is unclear whether increasing dietary antioxidant intake reduces the risk of COPD. Therefore, this study assessed the association between antioxidant intake and COPD in US adults aged ≥ 40 years and further examined the correlation using the Composite Dietary Antioxidant Index (CDAI).

Methods

The study included 8,257 US adults aged ≥ 40 years using data from the National Health and Nutrition Examination Survey (NHANES) for three cycles from 2007-2012. Multivariate logistic regression models were used to calculate the correlation between antioxidant intake and CDAI with COPD. Restricted cubic spline was further used to explore the exposure-response relationship. Mediation analysis was used to explore the role of inflammatory factors in the association between CDAI and COPD.

Results

This study included 8257 participants (4111 women [weighted, 50.7%]; mean [SD] age, 58.8 [11.2] years). In a multivariable-adjusted model of single antioxidant intake, a linear downward association between carotenoid intake and the incidence of COPD (P for trend = 0.052; Pnon- linear = 0.961). In a multivariable adjusted model for CDAI, this association is similarly present (P for trend = 0.018; Pnon-linear = 0.360). Multiple linear regression modeling showed that leukocytes (P = 0.002), alkaline phosphatase (P< 0.001), and c-reactive protein (P< 0.001) were negatively associated with CDAI levels. Meanwhile, mediation analysis revealed that alkaline phosphatase and c-reactive protein partially influenced the association between CDAI and COPD prevalence, with mediation ratios of 6.4% (P< 0.01) and 4.68% (P = 0.04), respectively.

Conclusion

The risk of COPD decreased with increased carotenoid intake and CDAI. In addition, CDAI has been found to be strongly associated with inflammatory factors and can reduce the incidence of COPD by mediating inflammatory factors.
Current understanding of macrophages in intracranial aneurysm: relevant etiological manifestations, signaling modulation and therapeutic strategies
Authors: Duan Jian , Zhao Qijie , He Zeyuan , Tang Shuang , Duan Jia , Xing Wenli
Published: January 2024

Macrophages activation and inflammatory response play crucial roles in intracranial aneurysm (IA) formation and progression. The outcome of ruptured IA is considerably poor, and the mechanisms that trigger IA progression and rupture remain to be clarified, thereby developing effective therapy to prevent subarachnoid hemorrhage (SAH) become difficult. Recently, climbing evidences have been expanding our understanding of the macrophages relevant IA pathogenesis, such as immune cells population, inflammatory activation, intra-/inter-cellular signaling transductions and drug administration responses. Crosstalk between macrophages disorder, inflammation and cellular signaling transduction aggravates the devastating consequences of IA. Illustrating the pros and cons mechanisms of macrophages in IA progression are expected to achieve more efficient treatment interventions. In this review, we summarized the current advanced knowledge of macrophages activation, infiltration, polarization and inflammatory responses in IA occurrence and development, as well as the most relevant NF-κB, signal transducer and activator of transcription 1 (STAT1) and Toll-Like Receptor 4 (TLR4) regulatory signaling modulation. The understanding of macrophages regulatory mechanisms is important for IA patients’ clinical outcomes. Gaining insight into the macrophages regulation potentially contributes to more precise IA interventions and will also greatly facilitate the development of novel medical therapy.
Global trends and research status in ankylosing spondylitis clinical trials: a bibliometric analysis of the last 20 years
Authors: Zhang Wenhui , Li Meng , Li Xuhao , Wang Xingxin , Liu Yuanxiang , Yang Jiguo
Published: January 2024

Background

Ankylosing spondylitis (AS) is a rheumatic and autoimmune disease associated with a chronic inflammatory response, mainly characterized by pain, stiffness, or limited mobility of the spine and sacroiliac joints. Severe symptoms can lead to joint deformity, destruction, and even lifelong disability, causing a serious burden on families and society as a whole. A large number of clinical studies have been published on AS over the past 20 years. This study aimed to summarize the current research status and global trends relating to AS clinical trials through a bibliometric analysis.

Methods

The Web of Science Core Collection database was searched for publications related to AS clinical trials published between January 2003 and June 2023. Bibliometric analysis and web visualization were performed using CiteSpace, VOSviewer, and a bibliometric online analysis platform (https://bibliometric.com), which included the number of publications, citations, countries, institutions, journals, authors, references, and keywords.

Results

1,212 articles published in 201 journals from 65 countries were included in this study. The number of publications related to AS clinical trials is increasing annually. The United States and the Free University of Berlin, the countries and institutions, respectively, that have published the most articles on AS, have made outstanding contributions to this field. The author with the most published papers and co-citations over the period covered by the study was Desiree Van Der Heijde. The journal with the most published and cited articles was Annals of the Rheumatic Diseases. The keywords: “double-blind,” “rheumatoid arthritis,” “efficacy,” “placebo-controlled trial,” “infliximab,” “etanercept,” “psoriatic arthritis” and “therapy” represent the current research hotspots regarding AS.

Discussion

This is the first study to perform a bibliometric analysis and visualization of AS clinical trial publications, providing a reliable research focus and direction for clinicians. Future studies in the field of AS clinical trials should focus on placebo-controlled trials of targeted therapeutic drugs.
A new target of radiotherapy combined with immunotherapy: regulatory T cells
Authors: Song Dongmei , Ding Yun
Published: January 2024

Radiotherapy is one important treatment for malignant tumours. It is widely believed today that radiotherapy has not only been used as a local tumour treatment method, but also can induce systemic anti-tumour responses by influencing the tumour microenvironment, but its efficacy is limited by the tumour immunosuppression microenvironment. With the advancement of technology, immunotherapy has entered a golden age of rapid development, gradually occupying a place in clinical tumour treatment. Regulatory T cells (Tregs) widely distributing in the tumour microenvironment play an important role in mediating tumour development. This article analyzes immunotherapy, the interaction between Tregs, tumours and radiotherapy. It briefly introduces immunotherapies targeting Tregs, aiming to provide new strategies for radiotherapy combined with Immunotherapy.
A metabolic perspective of the neutrophil life cycle: new avenues in immunometabolism
Authors: Thind Mehakpreet K. , Uhlig Holm H. , Glogauer Michael , Palaniyar Nades , Bourdon Celine , Gwela Agnes , Lancioni Christina L. , Berkley James A. , Bandsma Robert H. J. , Farooqui Amber
Published: January 2024

Neutrophils are the most abundant innate immune cells. Multiple mechanisms allow them to engage a wide range of metabolic pathways for biosynthesis and bioenergetics for mediating biological processes such as development in the bone marrow and antimicrobial activity such as ROS production and NET formation, inflammation and tissue repair. We first discuss recent work on neutrophil development and functions and the metabolic processes to regulate granulopoiesis, neutrophil migration and trafficking as well as effector functions. We then discuss metabolic syndromes with impaired neutrophil functions that are influenced by genetic and environmental factors of nutrient availability and usage. Here, we particularly focus on the role of specific macronutrients, such as glucose, fatty acids, and protein, as well as micronutrients such as vitamin B3, in regulating neutrophil biology and how this regulation impacts host health. A special section of this review primarily discusses that the ways nutrient deficiencies could impact neutrophil biology and increase infection susceptibility. We emphasize biochemical approaches to explore neutrophil metabolism in relation to development and functions. Lastly, we discuss opportunities and challenges to neutrophil-centered therapeutic approaches in immune-driven diseases and highlight unanswered questions to guide future discoveries.
Efficacy and safety of anakinra and canakinumab in PSTPIP1-associated inflammatory diseases: a comprehensive scoping review
Authors: Sanz-Cabanillas Juan Luis , Gómez-García Francisco , Gómez-Arias Pedro Jesús , Montilla-López Ana , Gay-Mimbrera Jesús , Ruano Juan , Isla-Tejera Beatriz , Parra-Peralbo Esmeralda
Published: January 2024

Introduction

This scoping review explores the effectiveness of IL-1 pathway inhibitors in managing PSTPIP1-associated inflammatory diseases (PAID). These diseases are marked by abnormal IL-1 pathway activation due to genetic mutations.

Methods

Our methodology adhered to a pre-published protocol and involved a thorough search of MEDLINE and EMBASE databases up to February 2022, following the Joanna Briggs Institute Reviewer’s Manual and the PRISMA Extension for Scoping Reviews. The review included studies reporting on IL-1 pathway inhibitor use in PAID patients.

Results

From an initial pool of 5,225 articles, 36 studies involving 43 patients were selected. The studies predominantly used observational designs and exhibited diversity in patient demographics, treatment approaches, and outcomes. Anakinra and canakinumab demonstrated promise in treating sterile pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) and PSTPIP1-associated myeloid-related-proteinemia inflammatory (PAMI) syndromes, with scant data on other syndromes. Notably, there was a paucity of information on the adverse effects of these treatments, necessitating cautious interpretation of their safety profile.

Conclusion

Current evidence on IL-1 pathway inhibitors for PAID is primarily from observational studies and remains limited. Rigorous research with larger patient cohorts is imperative for more definitive conclusions. Collaborative efforts among specialized research centers and international health initiatives are key to advancing this field.
High-frequency dynamics of pH, dissolved oxygen, and temperature in the coastal ecosystems of the Tanga-Pemba Seascape: implications for upwelling-enhanced ocean acidification and deoxygenation
Authors: George Rushingisha , Job Samson , Semba Masumbuko , Monga Elinasi , Lugendo Blandina , Tuda Arthur Omondi , Kimirei Ismael
Published: January 2024

Ocean acidification, deoxygenation, and warming are three interconnected global change challenges caused by increased anthropogenic carbon emissions. These issues present substantial threats to marine organisms, ecosystems, and the survival of coastal communities depending on these ecosystems. Coastal upwelling areas may experience significant declines in pH, dissolved oxygen (DO), and temperature levels during upwelling events, making marine organisms and ecosystems in these areas more susceptible to ocean acidification and deoxygenation. Understanding the dynamics of pH, DO, and temperature in coastal upwelling areas is essential for evaluating the susceptibility of resident organisms and ecosystems to lower pH and DO conditions occurring during upwelling events. To accomplish this, we used the pH and the DO loggers to measure high-frequency data for pH and DO, respectively, over six months in the open ocean and for a 24-hour cycle within the mangrove, seagrass, and coral reef ecosystems of the Tanga-Pemba Seascape (T-PS) during the northeast monsoon season. Our findings revealed the occurrence of multiple upwelling events, with varying durations, that result in significant declines in pH, DO, and temperature within the seascape. This is the first study to confirm the occurrence of multiple upwelling events in the T-PS. Moreover, the study has revealed a pH threshold value of 7.43 for ocean acidification in the T-PS. This is the first study to report a threshold value for ocean acidification in coastal upwelling areas of the Western Indian Ocean (WIO). Furthermore, it revealed that the extremely low levels of pH that occurred during upwelling events were above the pH threshold value of 7.43 for ocean acidification, while the extremely low levels of DO fell below the oxygen threshold value of 4.6 mg/L for deoxygenation. During upwelling events, seagrass and coral reef ecosystems, but not mangrove ecosystems, demonstrated elevated mean hourly values of pH and DO compared to those of the open ocean. These findings show that marine organisms and ecosystems in the T-PS are frequently exposed to lower pH and DO conditions due multiple upwelling events. However, their susceptibility to these conditions is reduced to some extent by the presence of seagrass meadows within these interconnected systems.
Prevention of exacerbation in patients with moderate-to-very severe COPD with the intent to modulate respiratory microbiome: a pilot prospective, multi-center, randomized controlled trial
Authors: Hua Jian-lan , Yang Zi-feng , Cheng Qi-jian , Han Yao-pin , Li Zheng-tu , Dai Ran-ran , He Bin-feng , Wu Yi-xing , Zhang Jing
Published: January 2024

Introduction

Considering the role of bacteria in the onset of acute exacerbation of COPD (AECOPD), we hypothesized that the use of influenza-Streptococcus pneumoniae vaccination, oral probiotics or inhaled amikacin could prevent AECOPD.

Methods

In this pilot prospective, muti-central, randomized trial, moderate-to-very severe COPD subjects with a history of moderate-to-severe exacerbations in the previous year were enrolled and assigned in a ratio of 1:1:1:1 into 4 groups. All participants were managed based on the conventional treatment recommended by GOLD 2019 report for 3 months, with three groups receiving additional treatment of inhaled amikacin (0.4 g twice daily, 5–7 days monthly for 3 months), oral probiotic Lactobacillus rhamnosus GG (1 tablet daily for 3 months), or influenza-S. pneumoniae vaccination. The primary endpoint was time to the next onset of moderate-to-severe AECOPD from enrollment. Secondary endpoints included CAT score, mMRC score, adverse events, and survival in 12 months.

Results

Among all 112 analyzed subjects (101 males, 96 smokers or ex-smokers, mean ± SD age 67.19 ± 7.39 years, FEV1 41.06 ± 16.09% predicted), those who were given dual vaccination (239.7 vs. 198.2 days, p = 0.044, 95%CI [0.85, 82.13]) and oral probiotics (248.8 vs. 198.2 days, p = 0.017, 95%CI [7.49, 93.59]) had significantly delayed onset of next moderate-to-severe AECOPD than those received conventional treatment only. For subjects with high symptom burden, the exacerbations were significantly delayed in inhaled amikacin group as compared to the conventional treatment group (237.3 vs. 179.1 days, p = 0.009, 95%CI [12.40,104.04]). The three interventions seemed to be safe and well tolerated for patient with stable COPD.

Conclusion

The influenza-S. pneumoniae vaccine and long-term oral probiotic LGG can significantly delay the next moderate-to-severe AECOPD. Periodically amikacin inhalation seems to work in symptomatic patients. The findings in the current study warrants validation in future studies with microbiome investigation.

Clinical trial registration:https://clinicaltrials.gov/, identifier NCT03449459.
Optimized protocol for quantification of extracellular nicotinamide adenine dinucleotide: evaluating clinical parameters and pre-analytical factors for translational research
Authors: Saqr Al-Hussein Ahmed , Kamali Can , Brunnbauer Philipp , Haep Nils , Koch Pia , Hillebrandt Karl-Herbert , Keshi Eriselda , Moosburner Simon , Mohr Raphael , Raschzok Nathanael , Pratschke Johann , Krenzien Felix
Published: January 2024

Nicotinamide adenine dinucleotide (NAD+), a coenzyme for more than 500 enzymes, plays a central role in energy production, metabolism, cellular signaling, and DNA repair. Until recently, NAD+ was primarily considered to be an intracellular molecule (iNAD+), however, its extracellular species (eNAD+) has recently been discovered and has since been associated with a multitude of pathological conditions. Therefore, accurate quantification of eNAD+ in bodily fluids such as plasma is paramount to answer important research questions. In order to create a clinically meaningful and reliable quantitation method, we analyzed the relationship of cell lysis, routine clinical laboratory parameters, blood collection techniques, and pre-analytical processing steps with measured plasma eNAD+ concentrations. Initially, NAD+ levels were assessed both intracellularly and extracellularly. Intriguingly, the concentration of eNAD+ in plasma was found to be approximately 500 times lower than iNAD+ in peripheral blood mononuclear cells (0.253 ± 0.02 μM vs. 131.8 ± 27.4 μM, p = 0.007, respectively). This stark contrast suggests that cellular damage or cell lysis could potentially affect the levels of eNAD+ in plasma. However, systemic lactate dehydrogenase in patient plasma, a marker of cell damage, did not significantly correlate with eNAD+ (n = 33; r = −0.397; p = 0.102). Furthermore, eNAD+ was negatively correlated with increasing c-reactive protein (CRP, n = 33; r = −0.451; p = 0.020), while eNAD+ was positively correlated with increasing hemoglobin (n = 33; r = 0.482; p = 0.005). Next, variations in blood drawing, sample handling and pre-analytical processes were examined. Sample storage durations at 4°C (0–120 min), temperature (0° to 25°C), cannula sizes for blood collection and tourniquet times (0 – 120 s) had no statistically significant effect on eNAD+ (p > 0.05). On the other hand, prolonged centrifugation (> 5 min) and a faster braking mode of the centrifuge rotor (< 4 min) resulted in a significant decrease in eNAD+ levels (p < 0.05). Taken together, CRP and hemoglobin appeared to be mildly correlated with eNAD+ levels whereas cell damage was not correlated significantly to eNAD+ levels. The blood drawing trial did not show any influence on eNAD+, in contrast, the preanalytical steps need to be standardized for accurate eNAD+ measurement. This work paves the way towards robust eNAD+ measurements, for use in future clinical and translational research, and provides an optimized hands-on protocol for reliable eNAD+ quantification in plasma.
Will it run?—A proof of concept for smoke testing decentralized data analytics experiments
Authors: Welten Sascha , Weber Sven , Holt Adrian , Beyan Oya , Decker Stefan
Published: January 2024

The growing interest in data-driven medicine, in conjunction with the formation of initiatives such as the European Health Data Space (EHDS) has demonstrated the need for methodologies that are capable of facilitating privacy-preserving data analysis. Distributed Analytics (DA) as an enabler for privacy-preserving analysis across multiple data sources has shown its potential to support data-intensive research. However, the application of DA creates new challenges stemming from its distributed nature, such as identifying single points of failure (SPOFs) in DA tasks before their actual execution. Failing to detect such SPOFs can, for example, result in improper termination of the DA code, necessitating additional efforts from multiple stakeholders to resolve the malfunctions. Moreover, these malfunctions disrupt the seamless conduct of DA and entail several crucial consequences, including technical obstacles to resolve the issues, potential delays in research outcomes, and increased costs. In this study, we address this challenge by introducing a concept based on a method called Smoke Testing, an initial and foundational test run to ensure the operability of the analysis code. We review existing DA platforms and systematically extract six specific Smoke Testing criteria for DA applications. With these criteria in mind, we create an interactive environment called Development Environment for AuTomated and Holistic Smoke Testing of Analysis-Runs (DEATHSTAR), which allows researchers to perform Smoke Tests on their DA experiments. We conduct a user-study with 29 participants to assess our environment and additionally apply it to three real use cases. The results of our evaluation validate its effectiveness, revealing that 96.6% of the analyses created and (Smoke) tested by participants using our approach successfully terminated without any errors. Thus, by incorporating Smoke Testing as a fundamental method, our approach helps identify potential malfunctions early in the development process, ensuring smoother data-driven research within the scope of DA. Through its flexibility and adaptability to diverse real use cases, our solution enables more robust and efficient development of DA experiments, which contributes to their reliability.