bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the value of various complex indexes of blood cell types and lipid levels in coronary heart disease
Authors: Peng Aihong , Zhang Bing , Wang Siyin , Feng Yujia , Liu Shengnan , Liu Cuiyi , Li Shu , Li Fei , Peng Yuanyuan , Wan Jing
Published: December 2023

Background

Inflammation and lipid infiltration play crucial roles in the development of atherosclerosis. This study aimed to investigate the association between various complex indexes of blood cell types and lipid levels with the severity of coronary artery stenosis and their predictive value in coronary heart disease (CHD).

Methods

The retrospective study was conducted on 3,201 patients who underwent coronary angiography at the Department of Zhongnan Hospital of Wuhan University. The patients were divided into two groups: CHD group and non-CHD group. The CHD group was further classified into three subgroups (mild, moderate, severe) based on the tertiles of their Gensini score or SYNTAX score I. Various complex indexes of blood cell types and lipid levels were compared between the groups.

Results

It revealed a positive correlation between all complex indexes and the severity of coronary artery stenosis. The systemic inflammation-response index/high-density lipoprotein cholesterol count (SIRI/HDL) exhibited the strongest correlation with both severity scores (Gensini score: r = 0.257, P < 0.001; SYNTAX score I: r = 0.171, P < 0.001). The monocyte to high-density lipoprotein cholesterol ratio (MHR) was identified as a stronger independent risk factor for CHD. However, SIRI/HDL had higher diagnostic efficacy for CHD (sensitivity 66.7%, specificity 60.4%, area under curve 0.680, 95% CI: 0.658–0.701). Notably, the pan-immune-inflammation value multiplied by low-density lipoprotein cholesterol count (PIV × LDL) exhibited the highest sensitivity of 85.2%.

Conclusion

All complex indexes which we investigated exhibited positive correlations with the severity of coronary artery stenosis. SIRI/HDL demonstrated higher diagnostic efficiency for CHD and a significant correlation with the severity of coronary artery stenosis.
Detection and quantification of pathogens in saliva of adolescents with cerebral palsy: a cross-sectional study
Authors: Yoshida Rosemeire Arai , Lobato Tiago Bertola , Gorjão Renata , França Lucas Santiago , Alves Lívia Araujo , Santos Maria Teresa Botti Rodrigues
Published: December 2023

Background

Elevated levels of inflammatory mediators in saliva have been described in individuals with cerebral palsy (CP).

Objective

The aim of this study was to detect and quantify the pathogens Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Prevotella intermedia in the saliva of adolescents with CP.

Methods

This is a cross-sectional study with adolescents with CP to detect periodontopathogens from saliva samples. Initially, saliva was collected from the CP (n = 34) and control groups (n = 31), followed by the gingival index (GI) for distribution of the groups of individuals with CP and control with gingivitis (bleeding on probing ≥ 10%) and without gingivitis. Bacterial DNA was extracted from saliva samples for detection of periodontopathogens by quantitative PCR (q-PCR). Data were analyzed by Mann–Whitney and Kruskal–Wallis tests, analysis of variance t-test (ANOVA) with Tukey–Kramer post-hoc tests (p < 0.05).

Results

The quantification of DNA of periodontopathogens in saliva samples showed that adolescents with CP present a variability (22.93–39.56) in the detection of P. gingivalis and that some subjects with CP and gingivitis (n = 4) present high quantification of P. gingivalis (ranging 39.56–37.65), although no significant difference was found between the groups (p > 0.05). A significant contrast was observed for the pathogen P. intermedia when comparing the difference in the control group (p = 0.0396). No major differences were detected in the quantification of periodontopathogens evaluated between the control group and CP.

Conclusion

Adolescents with CP showed variability in the detection of DNA of periodontopathogens, especially a great variation in the detection of P gingivalis in saliva of CP with gingivitis.
Effects of wildfire on soils: field studies and modelling on induced underground temperature variations
Authors: Chicco Jessica Maria , Mandrone Giuseppe , Vacha Damiano
Published: December 2023

Wildfire statistics report an increasing number of deaths, damages, and force society to face exceptional repair costs also due to secondary effects such as landslides, soils erosion and water quality problems. Literature agrees that the extent of the thermal disturbance of the soil due to wildfire is strongly dependent on fire intensity, on its duration and recurrence, as well as on fuel load, and soil properties. The unpredictability of these phenomena is one of the main challenges for scientists trying to study their characteristics. Degradation of the biological, chemical, and physical properties of forest soils due to the wildfires can reduce their capacity to function fully, with such effects either temporary or permanent. Direct measurements of the effects of these phenomena are difficult to be collected in the field, especially when the area affected by fires is a wilderness. In this study, controlled fires reproducing real conditions of wildfire affecting the Susa Valley (NW Italy) in 2017, which induced intense erosion and debris flows, have been monitored both above and below the ground surface. Moreover, numerical simulations based on real data increased the know-how to reproduce real changes on the underground. The small-scale fire simulations have allowed to verify how the depth affected by significant increases in temperatures is truly pellicular. Field tests show that at −2 cm depth temperature never exceed 70°C, meaning that it usually does not affect soil components or properties. The results of the study suggest that temperature variations in the subsoil are very localized and limited. If confirmed by further studies, the processes inferred to produce large ground effects on slopes after wildfires should be re-considered.
The potential association of peripheral inflammatory biomarkers in patients with papillary thyroid cancer before radioiodine therapy to clinical outcomes
Authors: Cao Jingjia , He Xiaoxi , Li Xiao , Sun Yaru , Zhang Wei , Li Yuyang , Zhu Xiaolu
Published: December 2023

Purpose

Neutrophil-lymphocyte ratio (NLR), markers-lymphocyte-to-monocyte ratio (LMR), and platelet to-lymphocyte ratio (PLR) have potential roles as prognostic biomarkers in various cancers. The study was evaluated to investigate the predictive value of the peripheral inflammatory biomarkers in patients with papillary thyroid carcinoma (PTC) before radioiodine therapy to the response of clinical outcomes.

Methods

We retrospectively analyzed the patients diagnosed with PTC at the Second Hospital of Shandong University between September 2018 and January 2020. Patients were divided into low and high inflammatory biomarker groups based on median values. The area under the receiver operating characteristic curves (ROC) and logistic regression were used to explore the potential risk factors.

Results

A total of 692 patients were enrolled, which included 197 (28.4%) males and 495 (71.6%) females. The median values of NLR, LMR and PLR of these patients were 1.7 (range 0.3–5.7), 7.1 (range 1.1–23.4) and 137.6 (range 27.6–497.5), respectively, and the mean values were 1.95 ± 0.82, 7.4 ± 2.5 and 148.7 ± 54.8, respectively. Compared to the lower PLR group, the higher group was significantly associated with gender, tumor size, N stage and thyroglobulin level (P<0.05). At the end of follow-up, 75.5% (523/692), 13.3% (91/692), 4.5% (31/692), and 6.7% (47/692) of patients were evaluated as excellent response (ER), indeterminate response (IDR), structural incomplete response (SIR), and biochemical incomplete response (BIR) respectively. In term of clinical outcomes, the NLR, LMR and PLR showed relatively low discriminative power (P≥0.05).

Conclusion

We found that higher PLR values was associated with poor clinicopathological features in PTC. However, the peripheral inflammatory indicators (NLR, LMR and PLR) may be insufficient to predict short-term clinical outcomes of patients with radioiodine therapy.
The impact of climate change policies on financial stability of China
Authors: Meng Zhaosu , Wang Xi , Ding Yao
Published: December 2023

Climate transition risks pose growing financial stability concerns, but research on quantifying climate policy impacts remains underexplored. This paper helps address this gap by evaluating how carbon tax (CT) and green supporting factor (GSF) influence China’s financial stability. An innovative dynamic stochastic general equilibrium (DSGE) model incorporating the banking sector is developed to quantify transmission channels, improving on conceptual studies. It reveals that more intense climate policies heighten impacts on financial stability, with CT improving it but GSF hampering it in the long run. However, both policies negatively affect stability initially, albeit insignificantly. These diagnostics underscore calibrating policy intensities and sequencing to balance climate and economic objectives. Furthermore, this study reveals asymmetric effects on polluting and non-polluting enterprises, with the former seeing reduced output and lending but the latter gaining. The differentiated approach proposed, tailored to firm emissions levels, provides key insights for unlocking smooth green transitions while maintaining financial system resilience. The paper makes important contributions by bringing together climate policies, adaptation, and financial stability. The findings offer insights into achieving a smooth climate transition while maintaining financial stability. Specific implications include starting with low CT on the heaviest emitters, gradually lowering risk weights for green lending, and using public incentives and investment to aid polluting firms’ transition. This study offers valuable quantitative insights for developing country-specific climate financial risk policies.
Quantifying the long-term recovery of the protective effect of forests against rockfall after stand-replacing disturbances
Authors: May Dominik , Moos Christine , Dorren Luuk , Noyer Estelle , Temperli Christian , Schwarz Massimiliano
Published: December 2023

Introduction

Increasing disturbances may significantly impact the long-term protective effect of forests against natural hazards. Quantifying the temporal development of the protective effect of forests is thus crucial for finding optimal management strategies.

Methods

In this study, we analyzed the long-term recovery of the protective effect of the secondary stands of spruce (Picea abies), fir (Abies alba), and beech (Fagus sylvatica) forests against rockfall after stand-replacing disturbances based on data of the Swiss National Forest Inventory (NFI). We therefore derived the age of the inventoried forest stands of those tree species based on a growth parametrization and quantified their energy dissipation capacity in rockfall processes as a function of stand age. We then analyzed the development of their protective factor for varying rockfall dispositions.

Results

Generally, it takes between 50 and 200 years to regain the maximum possible protective effect, depending from the site conditions and the rockfall disposition. This implies that the recovery of the protective effect after a severe disturbance may require more time than the decay of the protective effect from disturbance legacies, resulting in a long lasting gap of the provided protection.

Discussion

The here presented approach can serve as a basis to estimate the general range of recovery of the protective effect of beech, fir and spruce forests against rockfall provided by forest stands. Future research should analyse the effects of environmental and forest conditions as well as varying disturbance intensities and legacies to enable the assessment of specific trajectories of the short- and long-term recovery of the protective effect.
Responses of diversity and carbon and nitrogen cycling genes of soil microorganisms to pomegranate (Punica granatum L.)/faba bean (Vicia faba L.) intercropping
Authors: Zhang Degang , Zhu Dirui , Wang Miao , Shi Xian , Chen Yongchuan
Published: December 2023

The negative impacts of continuous cropping and long-term single crop planting on soil quality significantly restrict the high yield cultivation of perennial orchards. Intercropping can facilitate continuous cropping and improve the quality of the soil environment. However, it is still unclear whether the interplanting of faba bean in perennial orchards will increase the concentration of soil nutrients, change the composition of the soil microbial community, and increase the abundance of carbon (C) and nitrogen (N) cycling microorganisms. We interplanted faba beans in a perennial pomegranate orchard, and used sequencing and qPCR technology to study the effects on soil microbial diversity and C and N cycling genes. The results indicated that the interplanting of faba bean significantly increased the total N concentration by 28.6%, total phosphorus(P) concentration by 73.0% and available P concentration by 103.4%. The composition and structure of the soil microbial community were significantly changed, and the bacteria significantly enriched were Gaiellales and Rhizobiales at the order level and Nitrosomonadaceae at the family level. The fungi significantly enriched were Pezizomycetes at the class level, Pezizales and Sordariales at the order level, Ascodesmidaceae and Ophiocordycipitaceae at the family level, Cephaliophora, Parachaetomium, and Purpureocillium at the genus level, and Lilacinum, Lavendulum, Carinthiacum, Tropica, Chaetomium, and Delphinoides at the species level. The copy numbers of cbbL and nifH genes in soil were significantly increased by 79.9 and 168.5%, respectively. Changes in major nutrient elements explained 71.2% of the variance at the family level for bacteria and 46.0% of the variance at the family level for fungi. These results provided a scientific basis for the improvement of soil environmental quality and soil microorganisms by interplanting cash crops in perennial orchards.
Potential for quantifying general environmental resilience of dairy cattle in sub-Saharan Africa using deviations in milk yield
Authors: Oloo Richard D. , Mrode Raphael , Bennewitz Jörn , Ekine-Dzivenu Chinyere C. , Ojango Julie M. K. , Gebreyohanes Gebregziabher , Mwai Okeyo A. , Chagunda Mizeck G. G.
Published: December 2023

Introduction: Genetic improvement of general resilience of dairy cattle is deemed as a part of the solution to low dairy productivity and poor cattle adaptability in sub-Saharan Africa (SSA). While indicators of general resilience have been proposed and evaluated in other regions, their applicability in SSA remains unexplored. This study sought to test the viability of utilizing log-transformed variance (LnVar), autocorrelation (rauto), and skewness (Skew) of deviations in milk yield as indicators of general resilience of dairy cows performing in the tropical environment of Kenya.

Methods: Test-day milk yield records of 2,670 first-parity cows performing in three distinct agroecological zones of Kenya were used. To predict expected milk yield, quantile regression was used to model lactation curve for each cow. Subsequently, resilience indicators were defined based on actual and standardized deviations of observed milk yield from the expected milk yield. The genetic parameters of these indicators were estimated, and their associations with longevity and average test-day milk yield were examined.

Results: All indicators were heritable except skewness of actual and standardized deviation. The log-transformed variance of actual (LnVar1) and standardized (LnVar2) deviations had the highest heritabilities of 0.19 ± 0.04 and 0.17 ± 0.04, respectively. Auto-correlation of actual (rauto1) and standardized (rauto2) deviations had heritabilities of 0.05 ± 0.03 and 0.07 ± 0.03, respectively. Weak to moderate genetic correlations were observed among resilience indicators. Both rauto and Skew indicators had negligible genetic correlations with both longevity and average test-day milk yield. LnVar1 and LnVar2 were genetically associated with better longevity (rg = −0.47 ± 0.26 and −0.49 ± 0.26, respectively). Whereas LnVar1 suggested that resilient animals produce lower average test-day milk yield, LnVar2 revealed a genetic association between resilience and higher average test-day milk yield.

Discussion: Log transformed variance of deviations in milk yield holds a significant potential as a robust resilience indicator for dairy animals performing in SSA. Moreover, standardized as opposed to actual deviations should be employed in defining resilience indicators because the resultant indicator does not inaccurately infer that low-producing animals are inherently resilient. This study offers an opportunity for enhancing the productivity of dairy cattle performing in SSA through selective breeding for resilience to environmental stressors.
Attitudes toward pre-symptomatic screening for Alzheimer’s dementia in five European countries: a comparison of family members of people with Alzheimer’s dementia versus non-family members
Authors: Angelidou Ioanna A. , Makri Marina , Beyreuther Konrad , Boada Rovira Mercè , Despoti Akyllina , Engelborghs Sebastiaan , Miguel Andrea , Rodríguez Isabel , Stocker Hannah , Temmerman Joke , Tsolaki Magda , Yener Görsev , Yerlikaya Deniz , Teichmann Birgit
Published: December 2023

Introduction: Pre-symptomatic screening is getting more attention in healthcare as it detects the risk for developing neurodegenerative diseases like Alzheimer’s disease (AD), which is very useful for treatment or prevention. AD screening could play an important role in individuals with at least one affected first-degree relative, but also without family history. As the demand for screening is rising worldwide, it is important to consider possible cross-cultural differences in attitudes toward pre-symptomatic screening in order to tailor healthcare services to the needs of each country.

Objective: This study aims to investigate the attitudes of family members and non-family members of people with dementia toward pre-symptomatic screening and explore possible differences in attitudes across five European countries (Belgium, Germany, Greece, Spain, Turkey) using translated versions of the “Perceptions regarding pRE-symptomatic Alzheimer’s Disease Screening” questionnaire (PRE-ADS).

Methods: The multicultural sample (N = 650) was recruited from samples that were previously used in validation studies of the translated PRE-ADS versions. The subscale “Acceptability of Screening”, consisting of five PRE-ADS items to specifically explore willingness to undergo screening, was created. Ιnternal consistency was measured, and structural validity was determined using Confirmatory Factor Analysis (CFA). Group comparisons were performed to investigate differences in attitudes toward pre-symptomatic AD screening regarding family history and country of origin using the PRE-ADS and the “Acceptability of Screening” mean scores.

Results: Construct validity was acceptable for the PRE-ADS. Both the PRE-ADS (α = 0.76) and its subscale “Acceptability of Screening” (α = 0.90) had good internal consistency. Overall, 56.9% of the total sample expressed a positive intention toward pre-symptomatic AD screening. T-tests showed significantly higher mean scores of participants with an affected family member. An international comparison revealed differences in the “Acceptability of Screening” mean score across the five European countries. No cross-cultural differences were found for the PRE-ADS mean score after adjusting for confounding variables.

Conclusion: The PRE-ADS and its subscale are reliable tools for assessing pre-symptomatic AD screening attitudes. Variations in the acceptability of screening seem to be linked to family history and cultural influences. Further research with larger samples is needed to explore underlying relationships.
Efficacy and safety of sublingual versus subcutaneous immunotherapy in children with allergic rhinitis: a systematic review and meta-analysis
Authors: Yang Jiumei , Lei Sihong
Published: December 2023

Aim

To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR).

Methods

PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to March 2, 2023. Outcomes included symptom scores (SSs), medication scores (MSs), symptom and medication scores (SMSs), new sensitizations, development of asthma, improvement, and treatment-related adverse events (TRAEs). The quality of the included studies was assessed by the modified Jadad scale and Newcastle-Ottawa scale (NOS). Meta-regression was carried out to explore the source of heterogeneity. Subgroup analysis was further conducted in terms of study design [randomized controlled trials (RCTs), cohort studies], allergen [house dust mites (HDMs), grass pollen], treatment duration (≥ 24, 12-23 or < 12 months), allergen immunotherapy (AIT) modality (drops or tablets), and AIT protocol [continuous, pre-seasonal, co-seasonal, or after the grass pollen season (GPS)]. Sensitivity analysis was conducted for all outcomes. A Bayesian framework and a Monte Carlo Markov Chain (MCMC) model were developed for indirect comparison.

Results

Totally 50 studies with 10813 AR children were included, with 4122 treated with SLIT, 1852 treated with SCIT, and 4839 treated with non-SLIT or non-SCIT therapy. For direct comparison, the SLIT group had a similar SS to the SCIT group [pooled standardized mean difference (SMD): 0.41, 95% confidence interval (CI): -0.46, 1.28, P = 0.353]. Comparable MSs were observed in the SLIT and SCIT groups (pooled SMD: 0.82, 95%CI: -0.88, 2.53, P = 0.344). For indirect comparison, no significant differences were found in SSs (pooled SMD: 1.20, 95% credibility interval (CrI): -1.70, 4.10), MSs (pooled SMD: 0.57, 95%CrI: -1.20, 2.30), SMSs (pooled SMD: 1.80, 95%CrI: -0.005, 3.60), new sensitizations [pooled relative risk (RR): 0.34, 95%CrI: 0.03, 3.58], and development of asthma (pooled RR: 0.68, 95%CrI: 0.01, 26.33) between the SLIT and SCIT groups; the SLIT group illustrated a significantly lower incidence of TRAEs than the SCIT group (pooled RR: 0.17, 95%CrI: 0.11, 0.26).

Conclusion

Considering both efficacy and safety, SLIT might be a more favorable AIT than SCIT in the treatment of pediatric AR, which may serve as a decision-making reference for clinicians.

Systematic review registration

PROSPERO (CRD42023460693).
Sex-dependent differences in type I IFN-induced natural killer cell activation
Authors: Pujantell Maria , Skenteris Nikolaos-Taxiarchis , Claussen Janna Marieke , Grünhagel Benjamin , Thiele Rebecca-Jo , Altfeld Marcus
Published: December 2023

Natural killer (NK) cells are important antiviral effector cells and also involved in tumor clearance. NK cells express IFNAR, rendering them responsive to Type I IFNs. To evaluate Type I IFN-mediated modulation of NK cell functions, individual Type I IFNs subtypes were assessed for their ability to activate NK cells. Different Type I IFN subtypes displayed a broad range in the capacity to induce and modulate NK cell activation and degranulation, measured by CD69 and CD107a expression in response to leukemia cell line K562. When including biological sex as a variable in the analysis, transwell co-cultures of NK cells with either male- or female-derived PBMCs or pDCs stimulated with the TLR7/8 agonist CL097 showed that NK cells were more activated by CL097-stimulated cells derived from females. These sex-specific differences were linked to higher CL097-induced IFNα production by pDCs derived from females, indicating an extrinsic sex-specific effect of Type I IFNs on NK cell function. Interestingly, in addition to the extrinsic effect, we also observed NK cell-intrinsic sex differences, as female NK cells displayed higher activation levels after IFNα-stimulation and after co-culture with CL097-stimulated pDCs, suggesting higher activation of IFNα-signaling transduction in female NK cells. Taken together, the results from these studies identify both extrinsic and intrinsic sex-specific differences in Type I IFN-dependent NK cell functions, contributing to a better understanding of sex-specific differences in innate immunity.
Synergistic treatment strategy: combining CAR-NK cell therapy and radiotherapy to combat solid tumors
Authors: He Jie , Yan Yushan , Zhang Jun , Wei Zhiming , Li Huashun , Xing Ligang
Published: December 2023

Immunotherapy, notably chimeric antigen receptor (CAR) modified natural killer (NK) cell therapy, has shown exciting promise in the treatment of hematologic malignancies due to its unique advantages including fewer side effects, diverse activation mechanisms, and wide availability. However, CAR-NK cell therapies have demonstrated limited efficacy against solid tumors, primarily due to challenges posed by the solid tumor microenvironment. In contrast, radiotherapy, a well-established treatment modality, has been proven to modulate the tumor microenvironment and facilitate immune cell infiltration. With these observations, we hypothesize that a novel therapeutic strategy integrating CAR-NK cell therapy with radiotherapy could enhance the ability to treat solid tumors. This hypothesis aims to address the obstacles CAR-NK cell therapies face within the solid tumor microenvironment and explore the potential efficacy of their combination with radiotherapy. By capitalizing on the synergistic advantages of CAR-NK cell therapy and radiotherapy, we posit that this could lead to improved prognoses for patients with solid tumors.
Lineage tracing of T cell differentiation from T-iPSC by 2D feeder-free culture and 3D organoid culture
Authors: Ishiguro Yoshitaka , Iriguchi Shoichi , Asano Shinya , Shinohara Tokuyuki , Shiina Sara , Arima Suguru , Kassai Yoshiaki , Sakai Yoshiharu , Obama Kazutaka , Kaneko Shin
Published: December 2023

Introduction

T cells induced from induced pluripotent stem cells(iPSCs) derived from antigen-specific T cells (T-iPS-T cells) are an attractive tool for T cell immunotherapy. The induction of cytotoxic T-iPS-T cells is well established in feeder-free condition for the aim of off-the-shelf production, however, the induction of helper T-iPS-T cells remains challenging.

Methods

We analyzed T-iPS-T cells matured in 3D organoid culture at different steps in the culture process at the single-cell level. T-iPS-T cell datasets were merged with an available human thymocyte dataset based in single-cell RNA sequencing (scRNA-seq). Particularly, we searched for genes crucial for generation CD4+ T-iPS-T cells by comparing T-iPS-T cells established in 2D feeder-free or 3D organoid culture.

Results

The scRNA-seq data indicated that T-iPS-T cells are similar to T cells transitioning to human thymocytes, with SELENOW, GIMAP4, 7, SATB1, SALMF1, IL7R, SYTL2, S100A11, STAT1, IFITM1, LZTFL1 and SOX4 identified as candidate genes for the 2D feeder-free induction of CD4+ T-iPS-T cells.

Discussion

This study provides single cell transcriptome datasets of iPS-T cells and leads to further analysis for CD4+ T cell generation from T-iPSCs.
A review of skin immune processes in acne
Authors: Jin Zhongcai , Song Yujun , He Li
Published: December 2023

Acne vulgaris is one of the most prevalent skin conditions, affecting almost all teenagers worldwide. Multiple factors, including the excessive production of sebum, dysbiosis of the skin microbiome, disruption of keratinization within hair follicles, and local inflammation, are believed to trigger or aggravate acne. Immune activity plays a crucial role in the pathogenesis of acne. Recent research has improved our understanding of the immunostimulatory functions of microorganisms, lipid mediators, and neuropeptides. Additionally, significant advances have been made in elucidating the intricate mechanisms through which cutaneous innate and adaptive immune cells perceive and transmit stimulatory signals and initiate immune responses. However, our understanding of precise temporal and spatial patterns of immune activity throughout various stages of acne development remains limited. This review provides a comprehensive overview of the current knowledge concerning the immune processes involved in the initiation and progression of acne. Furthermore, we highlight the significance of detailed spatiotemporal analyses, including analyses of temporal dynamics of immune cell populations as well as single-cell and spatial RNA sequencing, for the development of targeted therapeutic and prevention strategies.
m6A methylation modification and immune cell infiltration: implications for targeting the catalytic subunit m6A-METTL complex in gastrointestinal cancer immunotherapy
Authors: Peng Chen , Xiong Fen , Pu Xi , Hu Zhangmin , Yang Yufei , Qiao Xuehan , Jiang Yuchun , Han Miao , Wang Deqiang , Li Xiaoqin
Published: December 2023

N6-methyladenosine (m6A) methylation modification is a ubiquitous RNA modification involved in the regulation of various cellular processes, including regulation of RNA stability, metabolism, splicing and translation. Gastrointestinal (GI) cancers are some of the world’s most common and fatal cancers. Emerging evidence has shown that m6A modification is dynamically regulated by a complex network of enzymes and that the catalytic subunit m6A-METTL complex (MAC)-METTL3/14, a core component of m6A methyltransferases, participates in the development and progression of GI cancers. Furthermore, it has been shown that METTL3/14 modulates immune cell infiltration in an m6A-dependent manner in TIME (Tumor immune microenvironment), thereby altering the response of cancer cells to ICIs (Immune checkpoint inhibitors). Immunotherapy has emerged as a promising approach for treating GI cancers. Moreover, targeting the expression of METTL3/14 and its downstream genes may improve patient response to immunotherapy. Therefore, understanding the role of MAC in the pathogenesis of GI cancers and its impact on immune cell infiltration may provide new insights into the development of effective therapeutic strategies for GI cancers.
Economic viability of a large vessel mesopelagic fishery under ecological uncertainty
Authors: Vastenhoud Berthe M. J. , Bastardie Francois , Andersen Ken H. , Speirs Douglas C. , Nielsen J. Rasmus
Published: December 2023

Motivated by the global rise in demand for marine products, there is increased interest in exploitation of the mesopelagic zone. However, the feasibility of this potential fishery remains uncertain, partly due to limited biological data and knowledge on sustainability of exploitation, and due to questions related to its economic viability. Consequently, there is a demand for better insights into these factors before any commencement of a fishery. Here we use the DISPLACE individual-vessel based bio-economic model to evaluate economic and biological trade-offs of a fishery on Maurolicus muelleri and Benthosema glaciale, the main potential target fish species in the mesopelagic zone of the Northeast Atlantic. We found that a fish price between 1.6-5.0 €/kg is necessary for mesopelagic resources to assure a profitable mesopelagic fishery, which is twice that expected for species with similar fat content. These high fish prices are necessary to cover the high fuel consumption costs due to the distant fishing grounds. Furthermore, the distance of the fishing grounds makes the fuel tank capacity a limiting factor for the fishery. A first evaluation of preliminary harvest control strategies indicated that a low fishing mortality of F = 0.2 year-1 resulted in the highest potential profitability of the fishery. Restriction of gear mesh sizes did not significantly affect the profitability of the fishery. We show that the current ecological uncertainties, especially regarding the life-history, species-specific and spatio-temporal abundance and distribution estimates have a significant impact on the estimates of potential viability of the fishery. It is therefore of the utmost importance to gain more insights in those factors before investments are made into the development of such fishery.
The causal relationship between risk of developing bronchial asthma and frailty: a bidirectional two-sample Mendelian randomization study
Authors: Ma Xiao , Xu Haoran , Xie Jinghui , Zhang Lu , Shi Mengyao , Li Zegeng
Published: December 2023

Background

A potential link between asthma and frailty has been suggested in previous studies. However, the nature of the causal relationship between these two conditions warrants further investigation. Therefore, this study assessed the bidirectional causality between asthma and frailty risk using two-sample Mendelian randomization (MR).

Methods

The study data were obtained from the genome-wide association study (GWAS) dataset, with 337,159 samples representing asthma data and 175,226 samples representing frailty. The causal relationship between the two disorders was assessed by selecting the single nucleotide polymorphisms (SNPs), significantly associated with both asthma and frailty. The inverse variance weighting (IVW) method was used as the main analytical method to estimate the possible influence of causality. Sensitivity analysis was also performed using Mr-Egger intercept, funnel plot, “leave-one-out,” and Cochran Q test. In addition, potential mediators were investigated by risk factor analysis.

Result

The IVW method showed an increased risk of frailty due to increased genetic susceptibility factors and the number of to asthma (OR = 2.325, 95%CI:1.958–2.761; p = 6.527498e-22), while no horizontal pleiotropy was observed for the Mr-Egger intercept (p = 0.609) and the funnel plot. The Cochran Q value was 72.858, p = 0.024, and there was heterogeneity in the Cochran Q-value. No single SNP was observed for “leave-one-out” that had a biasing effect on the instrumental variables. In addition, genetic susceptibility to frailty was associated with asthma (OR = 1.088, 95%CI:1.058–1.119; p = 4.815589e-09). In the causal relationship described above, several risk factors for frailty are complex, with asthma leading to a significant reduction in physical activity endurance.

Conclusion

Our findings suggest a probable positive causal effect of asthma on the risk of developing frailty, potentially mediated by reduced physical activity endurance. At the same time, a causal relationship exists between frailty and asthma. Therefore, assessment strategies for frailty should include asthma and vice versa.
High proportions of post-exertional malaise and orthostatic intolerance in people living with post-COVID-19 condition: the PRIME post-COVID study
Authors: Pagen Demi M. E. , Van Herck Maarten , van Bilsen Céline J. A. , Brinkhues Stephanie , Konings Kevin , den Heijer Casper D. J. , Spruit Martijn A. , Hoebe Christian J. P. A. , Dukers-Muijrers Nicole H. T. M.
Published: December 2023

Background

Exercise-based treatments can worsen/exacerbate symptoms in people who were SARS-CoV-2 positive and living with post-COVID-19 condition (PL-PCC) and who have post-exertional malaise (PEM) or orthostatic intolerance (OI). Nevertheless, PEM and OI are not routinely assessed by clinicians. We estimated PEM and OI proportions in PL-PCC, as well as in people not living with PCC (PnL-PCC) and negatives (i.e., never reported a SARS-CoV-2 positive test), and identified associated factors.

Methods

Participants from the Prevalence, Risk factors, and Impact Evaluation (PRIME) post-COVID-19 condition study were included. PEM and OI were assessed using validated questionnaires. PCC was defined as feeling unrecovered after SARS-CoV-2 infection. Multivariable regression analyses to study PEM and OI were stratified for sex.

Results

Data from 3,783 participants were analyzed. In PL-PCC, the proportion of PEM was 48.1% and 41.2%, and the proportion of OI was 29.3% and 27.9% in women and men, respectively. Proportions were higher in PL-PCC than negatives, for PEM in women OR=4.38 [95%CI:3.01–6.38]; in men OR = 4.78 [95%CI:3.13–7.29]; for OI in women 3.06 [95%CI:1.97-4.76]; in men 2.71 [95%CI:1.75–4.21]. Associated factors were age ≤ 60 years, ≥1 comorbidities, and living alone.

Conclusion

High proportions of PEM and OI are observed in PL-PCC. Standard screening for PEM and OI is recommended in PL-PCC to promote appropriate therapies.
Comparative analysis of nitrogen content and its influence on actinorhizal nodule and rhizospheric microorganism diversity in three Alnus species
Authors: Yuan Yuwei , Chen Zhi , Huang Xin , Wang Fang , Guo Hongying , Huang Zhen , Yang Hanbo
Published: December 2023

Alnus spp. (alder) are typical nonleguminous nitrogen-fixing trees that have a symbiotic relationship with Frankia. To explore the differences in nitrogen-fixing microorganisms between three alders (A. cremastogyne, A. glutinosa, and A. formosana) with different chromosome ploidies, the community structure and compositional diversity of potential nitrogen-fixing microorganism in root nodules and rhizosphere soil were comparatively analyzed using 16S rRNA and nitrogenase (nifH) gene sequencing. The nitrogen contents in the root nodules and rhizosphere soil were also determined. The results showed that the contents of total nitrogen and nitrate nitrogen in the root nodules of the three alders are significantly higher than those in the rhizosphere soils, while the ammonium nitrogen content show the opposite trend. The family, genus, and species levels showed obviously differences between root nodules and rhizosphere soils, while there were no significant differences at the classification level between the three alders. At the phylum level, the dominant phyla from 16S rRNA and nifH gene data in the root nodules and rhizosphere soil of the three alders are phylum Actinomycetota and phylum Pseudomonadota, respectively. The LEfSe results showed that there are significant differences in the dominant groups in the root nodules and rhizosphere oil of the three alders. The relative abundances of dominant groups also showed obvious differences between the root nodules and rhizosphere soils of three alders. The relative abundances of Frankia and unclassified_Frankia in root nodules are obviously higher than those in rhizosphere soils, and their relative abundances in A. glutinosa root nodules are significantly higher than those in A. cremastogyne and A. formosana at the genus and species levels. The diversity of potential nitrogen-fixing microorganism from 16S rRNA and nifH gene data in the A. glutinosa root nodules and rhizosphere soils are all higher than those in A. cremastogyne and A. formosana. The results of functional prediction also showed that the OTUs for nitrogen fixation, nitrate respiration, and ureolysis in A. glutinosa root nodules are higher than those in the other two alders. Redundancy analysis revealed that the total nitrogen content mostly affects the Frankia community. Overall, there are significant differences in the community composition and structure of potential nitrogen-fixing microorganism in the root nodules and rhizosphere soils between the three alders. A. glutinosa showed a relatively stronger nitrogen fixation capacity than A. formosana and A. cremastogyne. The results help elucidates how the community structure and nitrogen-fixing ability of potential nitrogen-fixing microorganism differ between alder species and serve as a reference for applying Frankia to alder plantations.
Avian influenza outbreaks in domestic cats: another reason to consider slaughter-free cell-cultured poultry?
Authors: Rzymski Piotr
Published: December 2023

Avian influenza causes substantial economic loss in the poultry industry and potentially threatens human health. Over recent years, the highly pathogenic avian influenza A/H5N1 virus has led to devastating losses in poultry flocks and wild birds. At the same time, the number of mammalian species identified to be infected with A/H5N1 is increasing, with recent outbreaks in domestic cats, including household individuals, evidenced in July 2023 in Poland, ultimately creating opportunities for the virus to adapt better to mammalian hosts, including humans. Overall, between 2003 and 2023, over 10 outbreaks in felids have been documented globally, and in six of them, feed based on raw chicken was suspected as a potential source of A/H5N1, fuelling a debate on threats posed by A/H5N1 and methods to decrease the associated risks. This article debates that technology allowing the production of slaughter-free meat, including poultry, from cell and tissue cultures could be considered as a part of a mitigation strategy to decrease the overall burden and threat of adaptation of avian influenza viruses to human hosts. By shifting poultry production to the cultured meat industry, the frequency of A/H5N1 outbreaks in farmed birds may be decreased, leading to a reduced risk of virus acquisition by wild and domesticated mammals that have direct contact with birds or eat raw poultry and have close contact with human (including domestic cats), ultimately minimizing the potential of A/H5N1 to adapt better to mammalian host, including humans. This adds to the list of other benefits of cultured meat that are also reviewed in this paper, including decreased antibiotic use, risk of microbial contamination and parasite transmission, and environmental and ethical advantages over conventional slaughtered meat. In conclusion, further development and implementation of this technology, also in the context of poultry production, is strongly advocated. Although cultured poultry is unlikely to replace the conventional process in the near future due to challenges with scaling up the production and meeting the continuously increased demand for poultry meat, it may still decrease the pressures and threats related to the transmission of highly pathogenic avian influenza in selected world regions.
Thalamic functional connectivity and sensorimotor processing in neurodevelopmental disorders
Authors: Karavallil Achuthan Smitha , Stavrinos Despina , Argueta Paula , Vanderburgh Caroline , Holm Haley B. , Kana Rajesh K.
Published: December 2023

One of the earliest neurobiological findings in autism has been the differences in the thalamocortical pathway connectivity, suggesting the vital role thalamus plays in human experience. The present functional MRI study investigated resting-state functional connectivity of the thalamus in 49 (autistic, ADHD, and neurotypical) young adults. All participants underwent structural MRI and eyes-open resting state functional MRI scans. After preprocessing the imaging data using Conn’s connectivity toolbox, a seed-based functional connectivity analysis was conducted using bilateral thalamus as primary seeds. Autistic participants showed stronger thalamic connectivity, relative to ADHD and neurotypical participants, between the right thalamus and right precentral gyrus, right pars opercularis-BA44, right postcentral gyrus, and the right superior parietal lobule (RSPL). Autistic participants also showed significantly increased connectivity between the left thalamus and the right precentral gyrus. Furthermore, regression analyses revealed a significant relationship between autistic traits and left thalamic-precentral connectivity (R2 = 0.1113), as well as between autistic traits and right postcentral gyrus and RSPL connectivity (R2 = 0.1204) in autistic participants compared to ADHD. These findings provide significant insights into the role of thalamus in coordinating neural information processing and its alterations in neurodevelopmental disorders.
Optimization of pharmacological interventions in the guinea pig animal model—a new approach to calculate the perilymph volume of the scala tympani
Authors: Grzybowski Marleen , Malfeld Kathrin , Lenarz Thomas , Scheper Verena , Schurzig Daniel
Published: December 2023

Objective

The guinea pig serves as a well-established animal model for inner ear research, offering valuable insights into the anatomy, physiology, and therapeutic interventions of the auditory system. However, the heterogeneity of results observed in both in-vivo experiments and clinical studies poses challenges in understanding and optimizing pharmacotherapy outcomes. This heterogeneity may be due to individual differences in the size of the guinea pig cochlea and thus in the volume of the scala tympani (ST), which can lead to different drug concentrations in the ST, a fact that has been largely overlooked thus far. To address this issue, we aimed to develop an approach for calculating the individual volume of perilymph within the ST before and after cochlear implant insertion.

Method

In this study, high-resolution μCT images of a total of n = 42 guinea pig temporal bones were used to determine the volume of the ST. We compared fresh, frozen, and fixed tissues from both colored and albino strains to evaluate the potential influence of tissue condition and strain on the results.

Results

Our findings demonstrate a variability in mean ST volume with a relative standard deviation (RSD) of 14.7%, comparable to studies conducted with humans (range RSD: 5 to 20%). This indicates that the guinea pig cochlea exhibits similar variability to that of the human cochlea. Consequently, it is crucial to consider this variability when designing and conducting studies utilizing the guinea pig as an animal model. Furthermore, we successfully developed a tool capable of estimating ST volume without the need for manual segmentation, employing two geometric parameters, basal diameter (A) and width (B) of the cochlea, corresponding to the cochlear footprint. The tool is available for free download and use on our website.

Conclusion

This novel approach provides researchers with a valuable tool to calculate individual ST volume in guinea pigs, enabling more precise dosing strategies and optimization of drug concentrations for pharmacotherapy studies. Moreover, our study underscores the importance of acknowledging and accounting for inter-individual variability in animal models to enhance the translational relevance and applicability of research outcomes in the field of inner ear investigations.
The prognostic value of Eastern Cooperative Oncology Group performance status on overall survival among patients with metastatic prostate cancer: a systematic review and meta-analysis
Authors: Assayag Jonathan , Kim Chai , Chu Haitao , Webster Jennifer
Published: December 2023

Background

There is heterogeneity in the literature regarding the strength of association between Eastern Cooperative Oncology Group performance status (ECOG PS) and mortality. We conducted a systematic review and meta-analysis of studies reporting the prognostic value of ECOG PS on overall survival (OS) in metastatic prostate cancer (mPC).

Methods

PubMed was searched from inception to March 21, 2022. A meta-analysis pooling the effect of ECOG PS categories (≥2 vs. <2, 2 vs. <2, and ≥1 vs. <1) on OS was performed separately for studies including patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC) using a random-effects model. Analyses were stratified by prior chemotherapy and study type.

Results

Overall, 75 studies, comprising 32,298 patients, were included. Most studies (72/75) included patients with mCRPC. Higher ECOG PS was associated with a significant increase in mortality risk, with the highest estimate observed among patients with mCRPC with an ECOG PS of ≥2 versus <2 (hazard ratio [HR]: 2.10, 95% confidence interval [CI]: 1.87–2.37). When stratifying by study type, there was a higher risk estimate of mortality among patients with mCRPC with an ECOG PS of ≥1 versus <1 in real-world data studies (HR: 1.98, 95% CI: 1.72–2.26) compared with clinical trials (HR: 1.32, 95% CI: 1.13–1.54; p < 0.001). There were no significant differences in the HR of OS stratified by previous chemotherapy.

Conclusion

ECOG PS was a significant predictor of OS regardless of category, previous chemotherapy, and mPC population. Additional studies are needed to better characterize the effect of ECOG PS on OS in mCSPC.