bluuebunny/crossref_metadata_2025 huggingface dataset:
Boxing-in of a blender in a Hénon-like family
Authors: Hittmeyer Stefanie , Krauskopf Bernd , Osinga Hinke M. , Shinohara Katsutoshi
Published: March 2023

Introduction

The extension of the Smale horseshoe construction for diffeomorphisms in the plane to those in spaces of at least dimension three may result in a hyperbolic invariant set referred to as a blender. The defining property of a blender is that it has a stable or unstable invariant manifold that appears to have a dimension larger than expected. In this study, we consider a Hénon-like family in ℝ3, which is the only explicitly given example of a system known to feature a blender in a certain range of a parameter (corresponding to an expansion or contraction rate). More specifically, as part of its hyperbolic set, this family has a pair of saddle fixed points with one-dimensional stable or unstable manifolds. When there is a blender, the closure of these manifolds cannot be avoided by one-dimensional curves coming from an appropriate direction. This property has been checked for the Hénon-like family by the method of computing extremely long pieces of global one-dimensional manifolds to determine the parameter range over which a blender exists.

Methods

In this study, we take the complimentary and local point of view of constructing an actual three-dimensional box (a parallelopiped) that acts as an outer cover of the hyperbolic set. The successive forward or backward images of this box form a nested sequence of sub-boxes that contains the hyperbolic set, as well as its respective local invariant manifold.

Results

This constitutes a three-dimensional horseshoe that, in contrast to the idealized affine construction, is quite general and features sub-boxes with curved edges. The initial box is defined in a parameter-dependent way, and this allows us to characterize properties of the hyperbolic set intuitively.

Discussion

In particular, we trace relevant edges of sub-boxes as a function of the parameter to provide additional geometric insight into when the hyperbolic set may or may not be a blender.
Mechanical alignment tolerance of a cruciate-retaining knee prosthesis under gait loading—A finite element analysis
Authors: Luan Yichao , Wang Huizhi , Fang Chaohua , Zhang Min , Li Junwei , Zhang Ningze , Liu Bolun , Su Jian , Cheng Cheng-Kung
Published: March 2023

Component alignment is one of the most crucial factors affecting total knee arthroplasty’s clinical outcome and survival. This study aimed to investigate how coronal, sagittal, and transverse malalignment affects the mechanical behavior of the tibial insert and to determine a suitable alignment tolerance on the coronal, sagittal, and transverse planes. A finite element model of a cruciate-retaining knee prosthesis was assembled with different joint alignments (−10°, −7°, −5°, −3°, 0°, 3°, 5°, 7°, 10°) to assess the effect of malalignment under gait loading. The results showed that varus or valgus, extension, internal rotation, and excessive external rotation malalignments increased the maximum Von Mises stress and contact pressure on the tibial insert. The mechanical alignment tolerance of the studied prosthesis on the coronal, sagittal, and transverse planes was 3° varus to 3° valgus, 0°–10° flexion, and 0°–5° external rotation, respectively. This study suggests that each prosthesis should include a tolerance range for the joint alignment angle on the three planes, which may be used during surgical planning.
Adsorption of textile dyes from aqueous solutions onto clay: Kinetic modelling and equilibrium isotherm analysis
Authors: Açıkyıldız Metin , Gürses Ahmet , Güneş Kübra , Şahin Elif
Published: March 2023

The commercial activated carbon commonly uses to reduce of dye amount in the textile industry effluents. In this study has focused on the use of a natural clay sample as low cost but potential adsorbent. For this purpose the adsorption of commercial textile dyes, Astrazon Red FBL and Astrazon Blue FGRL, onto clay was investigated. The physicochemical and topographic characteristics of natural clay sample were determined by scanning electron microscopy (SEM), X-Ray fluorescence spectrometry (XRF), X-Ray diffraction (XRD), thermogravimetric analysis (TGA), and cation exchange capacity measurements. It was determined that the major clay mineral was smectite with partial impurities. The effects of several operational parameters such as contact time, initial dye concentration, temperature, and adsorbent dosage on the adsorption process were evaluated. The adsorption kinetics was interpreted with pseudo-first order, pseudo-second order, and intra-particle diffusion models. The equilibrium adsorption data were analyzed using Langmuir, Freundlich, Redlich-Peterson, and Temkin isotherm models. It was determined that the adsorption equilibrium was reached in the first 60 min for each dye. The amount of adsorbed dyes onto clay decreased with increasing temperature, similarly, it decreased with increasing sorbent dosage. The kinetic data were well described by pseudo-second order kinetic model, and adsorption equilibrium data was followed both Langmuir and Redlich-Peterson models for each dyes. The adsorption enthalpy and entropy values were calculated as −10.7 kJ.mol−1 and −13.21 J.mol−1.K−1 for astrazon red and those for astrazon blue −11.65 kJ.mol−1 and 37.4 J.mol−1.K−1, respectively. The experimental results support that the physical interactions between clay particles and dye molecules have an important role for the spontaneous adsorption of textile dyes onto the clay. This study revealed that clay could effectively be used as an alternative adsorbent with high removal percentages of astrazon red and astrazon blue.
Vancomycin efficiency and safety of a dosage of 40–60 mg/kg/d and corresponding trough concentrations in children with Gram-positive bacterial sepsis
Authors: Peng Lengyue , Guo Ziyao , Zhang Guangli , Tian Xiaoyin , Gu Ruixue , Li Qinyuan , Li Yuanyuan , Luo Zhengxiu
Published: March 2023

Background

Optimal vancomycin trough concentrations and dosages remain controversial in sepsis children. We aim to investigate vancomycin treatment outcomes with a dosage of 40-60 mg/kg/d and corresponding trough concentrations in children with Gram-positive bacterial sepsis from a clinical perspective.

Methods

Children diagnosed with Gram-positive bacterial sepsis and received intravenous vancomycin therapy between January 2017 and June 2020 were enrolled retrospectively. Patients were categorized as success and failure groups according to treatment outcomes. Laboratory, microbiological, and clinical data were collected. The risk factors for treatment failure were analyzed by logistic regression.

Results

In total, 186 children were included, of whom 167 (89.8%) were enrolled in the success group and 19 (10.2%) in the failure group. The initial and mean vancomycin daily doses in failure group were significantly higher than those in success group [56.9 (IQR =42.1-60.0) vs. 40.5 (IQR =40.0-57.1), P=0.016; 57.0 (IQR =45.8-60.0) vs. 50.0 (IQR =40.0-57.6) mg/kg/d, P=0.012, respectively] and median vancomycin trough concentrations were similar between two groups [6.9 (4.0-12.1) vs.7.3 (4.5-10.6) mg/L, P=0.568)]. Moreover, there was no significant differences in treatment success rate between vancomycin trough concentrations ≤15 mg/L and >15 mg/L (91.2% vs. 75.0%, P=0.064). No vancomycin-related nephrotoxicity adverse effects occurred among all enrolled patients. Multivariate analysis revealed that a PRISM III score ≥10 (OR =15.011; 95% CI: 3.937-57.230; P<0.001) was the only independent clinical factor associated with increased incidence of treatment failure.

Conclusions

Vancomycin dosages of 40-60 mg/kg/d are effective and have no vancomycin-related nephrotoxicity adverse effects in children with Gram-positive bacterial sepsis. Vancomycin trough concentrations >15 mg/L are not an essential target for these Gram-positive bacterial sepsis patients. PRISM III scores ≥10 may serve as an independent risk factor for vancomycin treatment failure in these patients.
Cumulative live birth rates and birth outcomes after IVF/ICSI treatment cycles in young POSEIDON patients: A real-world study
Authors: Yan Enqi , Li Wenxuan , Jin Huizi , Zhao Mengya , Chen Dan , Hu Xinyao , Chu Yifan , Guo Yaxin , Jin Lei
Published: March 2023

Objective

The aim of this study was to describe the cumulative live birth rates (CLBRs) of young women with or without low prognosis according to the POSEIDON criteria after IVF/ICSI cycles and to investigate whether the diagnosis of low prognosis increases the risk of abnormal birth outcomes.

Design

Retrospective study.

Setting

A single reproductive medicine center.

Population

From January 2016 to October 2020, there were 17,893 patients (<35 years) involved. After screening, 4,105 women were included in POSEIDON group 1, 1,375 women were included in POSEIDON group 3, and 11,876 women were defined as non-POSEIDON.

Intervention(s)

Baseline serum AMH level was measured on the D2–D3 of menstrual cycle before IVF/ICSI treatment.

Main outcome measure(s)

Cumulative live birth rate (CLBR), birth outcomes.

Result(s)

After four stimulation cycles, the CLBRs in POSEIDON group 1, POSEIDON group 3, and non-POSEIDON group reached 67.9% (95% CI, 66.5%–69.3%), 51.9% (95% CI, 49.2%–54.5%), and 79.6% (95% CI, 78.9%–80.3%), respectively. There was no difference in gestational age, preterm delivery, cesarean delivery, and low birth weight infants between the three groups, but macrosomia was significantly higher in non-POSEIDON group, after adjusting for maternal age and BMI.

Conclusion(s)

The POSEIDON group shows lower CLBRs than the non-POSEIDON group in young women, while the risk of abnormal birth outcomes in the POSEIDON group will not increase.
The effect of environmental stressors on growth in fish and its endocrine control
Authors: Canosa Luis Fabián , Bertucci Juan Ignacio
Published: March 2023

Fish body growth is a trait of major importance for individual survival and reproduction. It has implications in population, ecology, and evolution. Somatic growth is controlled by the GH/IGF endocrine axis and is influenced by nutrition, feeding, and reproductive-regulating hormones as well as abiotic factors such as temperature, oxygen levels, and salinity. Global climate change and anthropogenic pollutants will modify environmental conditions affecting directly or indirectly fish growth performance. In the present review, we offer an overview of somatic growth and its interplay with the feeding regulatory axis and summarize the effects of global warming and the main anthropogenic pollutants on these endocrine axes.
Association between soluble neprilysin and diabetes: Findings from a prospective longitudinal study
Authors: Hu Junting , Zhu Hanyun , Dai Yunlang , Liu Yang , Lu Ying , Zhu Shasha , Chen Linan , Zhang Mingzhi , Jiang Tingbo , Peng Hao
Published: March 2023

Background

The potential role of neprilysin (NEP) in glucose metabolism has been found by basic studies but lacks population evidence. The objective of this study was to examine the association between serum NEP and diabetes in Chinese adults.

Methods

In a prospective longitudinal cohort study – the Gusu cohort (n=2,286, mean age: 52 years, 61.5% females), the cross-sectional, longitudinal, and prospective associations between serum NEP and diabetes were systemically examined by logistic regression adjusting for conventional risk factors. Serum NEP was measured at baseline using commercial ELISA assays. Fasting glucose was repeatedly measured 4 years apart.

Results

The cross-sectional analysis found a positive association between serum NEP and fasting glucose at baseline (β=0.08, P=0.004 for log-transformed NEP). This association persisted after controlling for the dynamic risk profiles during follow-up (β=0.10, P=0.023 for log-transformed NEP). The prospective analysis found that a higher level of serum NEP at baseline was associated with a higher risk of diabetes during follow-up (OR=1.79, P=0.039 for log-transformed NEP).

Conclusions

Serum NEP was not only associated with prevalent diabetes but also predicted the future risk of diabetes development in Chinese adults, independent of many behavioral and metabolic factors. Serum NEP may be a predictor and even a new therapeutic target for diabetes. However, the casualty and mechanisms of NEP in the development of diabetes require further investigation.
Normocalcemic primary hyperparathyroidism is an early stage of primary hyperparathyroidism according to fibroblast growth factor 23 level
Authors: Chertok Shacham Elena , Maman Nimra , Lazareva Tatyana , Masalha Refaat , Mahagna Lila , Sela Gala , Ishay Avraham
Published: March 2023

Introduction

Normocalcemic primary hyperparathyroidism is a variant of primary hyperparathyroidism with consistently normal albumin-adjusted or free-ionized calcium levels. It may be an early stage of classic primary hyperparathyroidism or could represent primary kidney or bone disorder characterized by permanent elevation of PTH level.

Aim of the study

The study aims to compare the FGF-23 levels in patients with PHPT, NPHPT, and normal calcium and PTH levels.

Methods

Our study included patients who were referred to the endocrinology clinic with a presumptive diagnosis of primary hyperparathyroidism, an isolated increased level of PTH, or reduced bone densitometry. For each patient, we performed blood analysis of FGF-23, calcium, phosphate, vitamin D [25(OH)D3], estimated glomerular filtration rate (eGFR), bone turnover markers, and urine analysis for calcium/creatinine ratio.

Results

Our study included 105 patients. Thirty patients with hypercalcemic hyperparathyroidism (HPHPT group), thirty patients with elevated PTH and normal calcium levels (NPHPT group), and 45 patients with normal calcium and PTH levels in the control group. FGF 23 level was 59.5± 23 pg/ml in the NPHPT group, 77 ± 33 pg/ml in the HPHPT group, and 49.7 ± 21.7 pg/ml in the control group (p=0.012). The phosphate level was lowest in the HPHPT group: 2.9 ± 0.6 vs 3.5 ± 0.44 in the NPHPT and 3.8 ± 0.5 in the control groups (p=0.001). No differences were found in eGFR, 25(OH)D3, C-terminal telopeptide type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels, and bone densitometry scores between the three study groups.

Conclusion

Our findings suggest that NPHPT is an early stage of PHPT. Further studies are needed to determine the role of FGF-23 and its usefulness in NPHPT.
Population structure and selective signature of sheep around Tarim Basin
Authors: Zhang Jihu , Zhang Cheng-long , Tuersuntuohe Mirenisa , Liu Shudong
Published: March 2023

Extreme climate change may lead to a decline in biodiversity and species extinction. And it also results in different population structure and genetic diversity of sheep. Therefore, studying the effects of extreme climate change on the distribution pattern of sheep is of great value. We used Illumina Ovine SNP 50K BeadChip to study the sheep around in southern Xinjiang of China, living around the Taklimakan Desert. Among them, 6 sheep breeds were from Xinjiang, China, and 3 sheep breeds were from other countries (Indian, Iran and Bangladeshi). We examined their genetic diversity and population structure and Genes related to year-round estrous in sheep were obtained by selective sweep. The principal component analysis, Admixture and Neighbor-Joining tree showed that a distinct pattern of population structure was observed in 9 sheep breeds. The candidate genes related to year-round estrous were ZO2, IGF1, TSHB and DLG1, and the candidate genes related to sheep reproductive performance were BMP4, LRP8, NF1, and INSL3. This study contributes to a better understanding of the genetic structure and population history of sheep populations in the Taklimakan Desert environment, as well as the regulatory mechanisms of year-round estrous in sheep in the desert environment, which has important implications for the global livestock industry to cope with the challenges of rapidly changing climate and to explore important economic traits.
Eucalyptus woodlot adoption and its determinants in the Mecha District, Northern Ethiopia
Authors: Alemayehu Asabeneh , Melka Yoseph , Eshete Abeje
Published: March 2023

Introduction

The land area under Eucalyptus plantations has now significantly increased among Ethiopian smallholder farmers whereby Eucalyptus is grown on their farms in the form of a woodlot primarily for income generation. Despite its widespread adoption, studies and systematic documentation on its adoption and economic impact are inadequate to inform evidence-based policy development. The purpose of this study was to investigate the variables influencing the adoption of Eucalyptus woodlot in Mecha District, northern Ethiopia.

Methods

A multistage sampling method was used to sample 186 respondent households from three villages namely Enashenifalen, Addisameba, and Rim in the district. Primary data was gathered through key informants (13), in-depth interviews, focus group discussions (3), and direct observations, which were complemented by data from secondary sources obtained from published and unpublished documents. A double-hurdle econometric model was used to identify factors influencing households’ adoption decisions and adoption intensity of Eucalyptus woodlot.

Results and discussion

The findings indicate that household adoption decisions are significantly influenced by the number of parcels of land, off-farm work engagement, credit availability, and farmers’ perceptions of woodlot production. Family size (negatively), land holding size, number of parcels of land, market access, the adjacent farm, and farmers’ perceptions of Eucalyptus woodlot production all significantly influenced the adoption intensity of Eucalyptus woodlots. Furthermore, the major constraints were a lack of support and training, a lack of land segregation, and limited technologies. Providing support and training, alternative options for farmers, cluster planting, technology adoption, developing and implementing Eucalyptus policies, and enforcing rules and regulations are all areas that need to be addressed to improve the livelihood of the community.
Tree regeneration and spatial patterning among midtolerant tree species following gap-based harvesting in a temperate hardwood forest
Authors: Schnake David K. , Forrester Jodi A. , Sánchez Meador Andrew J. , Mladenoff David J. , Lorimer Craig G.
Published: March 2023

Introduction

Field experiments of gap-based harvest systems in temperate northern hardwood forests have provided inconsistent support for the theory that such regeneration approaches can improve regeneration success among increasingly underrepresented tree species intermediate in shade tolerance. We established a field experiment in Wisconsin, USA testing the long-term response of tree regeneration to group selection harvesting that created small (50 m2–D:H 0.32), medium (200 m2—D:H 0.64) and large (380 m2—D:H 0.88) gaps.

Materials and methods

Light levels were modeled to test the assumption of resource heterogeneity within and across these gap sizes. Spatial statistics were used to assess whether the point patterns of saplings of several midtolerant tree species (Betula alleghaniensis, Carya cordiformis, Fraxinus spp.) mapped in harvest gaps provided evidence for partitioning across resource gradients 9 years post-harvest. Finally, we measured occurrence and height of all saplings within the harvest gaps to test the effects of gap size and deer exclusion fencing on the density and total height of shade-tolerant and midtolerant tree regeneration.

Results and discussion

Light levels progressively increased with gap size, varied by position within gaps, and provided significant evidence of resource heterogeneity. The complex light gradients formed both within and across the three gap sizes may partially explain the statistically significant clustering of Fraxinus spp. saplings in gap centers and north and east into the forested edge of medium and large gaps, C. cordiformis on the west sides of forested transitions surrounding large gaps, and B. alleghaniensis in the centers of large gaps. Densities of tolerant and midtolerant saplings were similar in medium and large gaps after nine growing seasons, though tolerant saplings averaged two meters taller across all three gap sizes. Our results show that gap-based silvicultural systems can create resource gradients that are sufficient to regenerate mixtures of species with high to intermediate tolerance of shade. However, prescriptions beyond harvesting and deer exclusion fencing may be necessary for the recruitment of midtolerant species to canopy positions.
Frequencies of variants in genes associated with dyslipidemias identified in Costa Rican genomes
Authors: Valverde-Hernández Juan Carlos , Flores-Cruz Andrés , Chavarría-Soley Gabriela , Silva de la Fuente Sandra , Campos-Sánchez Rebeca
Published: March 2023

Dyslipidemias are risk factors in diseases of significant importance to public health, such as atherosclerosis, a condition that contributes to the development of cardiovascular disease. Unhealthy lifestyles, the pre-existence of diseases, and the accumulation of genetic variants in some loci contribute to the development of dyslipidemia. The genetic causality behind these diseases has been studied primarily on populations with extensive European ancestry. Only some studies have explored this topic in Costa Rica, and none have focused on identifying variants that can alter blood lipid levels and quantifying their frequency. To fill this gap, this study focused on identifying variants in 69 genes involved in lipid metabolism using genomes from two studies in Costa Rica. We contrasted the allelic frequencies with those of groups reported in the 1000 Genomes Project and gnomAD and identified potential variants that could influence the development of dyslipidemias. In total, we detected 2,600 variants in the evaluated regions. However, after various filtering steps, we obtained 18 variants that have the potential to alter the function of 16 genes, nine variants have pharmacogenomic or protective implications, eight have high risk in Variant Effect Predictor, and eight were found in other Latin American genetic studies of lipid alterations and the development of dyslipidemia. Some of these variants have been linked to changes in blood lipid levels in other global studies and databases. In future studies, we propose to confirm at least 40 variants of interest from 23 genes in a larger cohort from Costa Rica and Latin American populations to determine their relevance regarding the genetic burden for dyslipidemia. Additionally, more complex studies should arise that include diverse clinical, environmental, and genetic data from patients and controls and functional validation of the variants.
Bioinformatics-integrated screening of systemic sclerosis-specific expressed markers to identify therapeutic targets
Authors: Jin Jiahui , Liu Yifan , Tang Qinyu , Yan Xin , Jiang Miao , Zhao Xu , Chen Jie , Jin Caixia , Ou Qingjian , Zhao Jingjun
Published: March 2023

Background

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by extensive skin fibrosis. There are no effective treatments due to the severity, multiorgan presentation, and variable outcomes of the disease. Here, integrated bioinformatics was employed to discover tissue-specific expressed hub genes associated with SSc, determine potential competing endogenous RNAs (ceRNA) regulatory networks, and identify potential targeted drugs.

Methods

In this study, four datasets of SSc were acquired. To identify the genes specific to tissues or organs, the BioGPS web database was used. For differentially expressed genes (DEGs), functional and enrichment analyses were carried out, and hub genes were screened and shown in a network of protein-protein interactions (PPI). The potential lncRNA–miRNA–mRNA ceRNA network was constructed using the online databases. The specifically expressed hub genes and ceRNA network were validated in the SSc mouse and in normal mice. We also used the receiver operating characteristic (ROC) curve to determine the diagnostic values of effective biomarkers in SSc. Finally, the Drug-Gene Interaction Database (DGIdb) identified specific medicines linked to hub genes.

Results

The pooled datasets identified a total of 254 DEGs. The tissue/organ-specifically expressed genes involved in this analysis are commonly found in the hematologic/immune system and bone/muscle tissue. The enrichment analysis of DEGs revealed the significant terms such as regulation of actin cytoskeleton, immune-related processes, the VEGF signaling pathway, and metabolism. Cytoscape identified six gene cluster modules and 23 hub genes. And 4 hub genes were identified, including Serpine1, CCL2, IL6, and ISG15. Consistently, the expression of Serpine1, CCL2, IL6, and ISG15 was significantly higher in the SSc mouse model than in normal mice. Eventually, we found that MALAT1-miR-206-CCL2, let-7a-5p-IL6, and miR-196a-5p-SERPINE1 may be promising RNA regulatory pathways in SSc. Besides, ten potential therapeutic drugs associated with the hub gene were identified.

Conclusions

This study revealed tissue-specific expressed genes, SERPINE1, CCL2, IL6, and ISG15, as effective biomarkers and provided new insight into the mechanisms of SSc. Potential RNA regulatory pathways, including MALAT1-miR-206-CCL2, let-7a-5p-IL6, and miR-196a-5p-SERPINE1, contribute to our knowledge of SSc. Furthermore, the analysis of drug-hub gene interactions predicted TIPLASININ, CARLUMAB and BINDARIT as candidate drugs for SSc.
A cuproptosis random forest cox score model-based evaluation of prognosis, mutation characterization, immune infiltration, and drug sensitivity in hepatocellular carcinoma
Authors: Liu Ruiqi , Liu Yingyi , Zhang Fengyue , Wei Jinrui , Wu Lichuan
Published: March 2023

Background

Hepatocellular carcinoma is the third most deadly malignant tumor in the world with a poor prognosis. Although immunotherapy represents a promising therapeutic approach for HCC, the overall response rate of HCC patients to immunotherapy is less than 30%. Therefore, it is of great significance to explore prognostic factors and investigate the associated tumor immune microenvironment features.

Methods

By analyzing RNA-seq data of the TCGA-LIHC cohort, the set of cuproptosis related genes was extracted via correlation analysis as a generalization feature. Then, a random forest cox prognostic model was constructed and the cuproptosis random forest cox score was built by random forest feature filtering and univariate multivariate cox regression analysis. Subsequently, the prognosis prediction of CRFCS was evaluated via analyzing data of independent cohorts from GEO and ICGC by using KM and ROC methods. Moreover, mutation characterization, immune cell infiltration, immune evasion, and drug sensitivity of CRFCS in HCC were assessed.

Results

A cuproptosis random forest cox score was built based on a generalization feature of four cuproptosis related genes. Patients in the high CRFCS group exhibited a lower overall survival. Univariate multivariate Cox regression analysis validated CRFCS as an independent prognostic indicator. ROC analysis revealed that CRFCS was a good predictor of HCC (AUC =0.82). Mutation analysis manifested that microsatellite instability (MSI) was significantly increased in the high CRFCS group. Meanwhile, tumor microenvironment analysis showed that the high CRFCS group displayed much more immune cell infiltration compared with the low CRFCS group. The immune escape assessment analysis demonstrated that the high CRFCS group displayed a decreased TIDE score indicating a lower immune escape probability in the high CRFCS group compared with the low CRFCS group. Interestingly, immune checkpoints were highly expressed in the high CRFCS group. Drug sensitivity analysis revealed that HCC patients from the high CRFCS group had a lower IC50 of sorafenib than that from the low CRFCS group.

Conclusions

In this study, we constructed a cuproptosis random forest cox score (CRFCS) model. CRFCS was revealed to be a potential independent prognostic indicator of HCC and high CRFCS samples showed a poor prognosis. Interestingly, CRFCS were correlated with TME characteristics as well as clinical treatment efficacy. Importantly, compared with the low CRFCS group, the high CRFCS group may benefit from immunotherapy and sorafenib treatment.
Primary immunodeficiencies (PID) Life Index in Southeast Asia: A comparative analysis of PID Principles of Care (PoC)
Authors: Chan Chee Mun , Mahlaoui Nizar , Sánchez−Ramón Silvia , Pergent Martine , Solis Leire , Prevot Johan , Ali Adli
Published: March 2023

Objective

To analyze the implementation of the Principles of Care (PoC) in primary immunodeficiencies (PID) in Southeast Asia (SEA) countries - six years after its call of action.

Methodology

Using the newly developed PID Life Index software, the index of implementation of principles of care in the management of PIDs patients involving the six participating SEA countries (Cambodia, Indonesia, Malaysia, Vietnam, Thailand, and Philippines) were extracted. For each of the six separate principles, the index from the six countries will be compared and presented based on the calculated index.

Results

Comparative analysis of the six principles of care of PID in the SEA countries showed low diagnostic rate with minimal availability of diagnostic tests options. Generally, almost all SEA countries provide curative treatments, vaccines, and anti-infectious therapies although the reimbursement scheme varied in relieving patients’ financial burden. We also highlighted the active involvement of patient organizations in SEA, with main areas of work focused on advocacy and increasing awareness among public and healthcare professionals.

Discussion and conclusion

It is applaudable that the SEA continent is gradually strengthening its work in management of PID, especially in Thailand and Vietnam. However, more emphasis must be placed among stakeholders in SEA countries towards successful implementation of the PoC for a holistic management of PID patients.
Diagnostic value of anti-Kaiso autoantibody in axial spondyloarthritis
Authors: Feng Xinzhe , Tong Wenwen , Li Jia , Xu Yihong , Zhu Shanbang , Xu Weidong
Published: March 2023

Objective

Axial spondyloarthritis (axSpA) is a chronic rheumatic disease predominantly characterized by inflammation and progressive structural damage. Patients are often diagnosed very late, which delays the optimal treatment period. Early diagnosis of axSpA, especially non-radiographic axSpA (nr-axSpA), remains a major challenge. This study aimed to investigate the diagnostic value of anti-Kaiso autoantibodies in axSpA and their correlation with clinical disease indicators.

Methods

Two pooled serum samples (seven patients with nr-axSpA and seven healthy controls) were profiled using HuProt arrays to investigate the diagnostic value of autoantibodies in nr-axSpA. Levels of anti-Kaiso autoantibodies in patients with axSpA and controls were determined using the Meso Scale Discovery assay system. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of anti-Kaiso autoantibodies in axSpA. Pearson’s correlation was used to assess the correlation between anti-Kaiso autoantibodies and clinical parameters.

Results

Seven candidate autoantibodies were present in the serum of patients with nr-axSpA. The levels of anti-Kaiso autoantibodies were significantly higher in the nr-axSpA group than in the other groups. It can differentiate nr-axSpA from ankylosing spondylitis (AS), healthy controls, and rheumatoid arthritis. The level of early-stage AS among patients with nr-axSpA decreased when they progressed to the late stage. Of all patients with axSpA, serum anti-Kaiso autoantibody levels were positively correlated with the C-reactive protein level and the Bath Ankylosing Spondylitis Disease Activity Index score and negatively correlated with disease duration.

Conclusion

Anti-Kaiso autoantibody may be a valuable diagnostic biomarker for early-stage AS in the nr-axSpA period and may be a potential therapeutic target.
Gene expression changes in therapeutic ultrasound-treated venous leg ulcers
Authors: Boerman Olivia , Abedin Zahidur , DiMaria-Ghalili Rose Ann , Weingarten Michael S. , Neidrauer Michael , Lewin Peter A. , Spiller Kara L.
Published: March 2023

Introduction

Low-frequency, low-intensity ultrasound has been previously shown to promote healing of chronic wounds in humans, but mechanisms behind these effects are poorly understood. The purpose of this study was to evaluate gene expression differences in debrided human venous ulcer tissue from patients treated with low-frequency (20 kHz), low-intensity (100 mW/cm2) ultrasound compared to a sham treatment in an effort to better understand the potential biological mechanisms.

Methods

Debrided venous ulcer tissue was collected from 32 subjects one week after sham treatment or low-frequency, low-intensity ultrasound treatment. Of these samples, 7 samples (3 ultrasound treated and 4 sham treated) yielded sufficient quality total RNA for analysis by ultra-high multiplexed PCR (Ampliseq) and expression of more than 24,000 genes was analyzed. 477 genes were found to be significantly differentially expressed between the ultrasound and sham groups using cut-off values of p < 0.05 and fold change of 2.

Results and Discussion

The top differentially expressed genes included those involved in regulation of cell metabolism, proliferation, and immune cell signaling. Gene set enrichment analysis identified 20 significantly enriched gene sets from upregulated genes and 4 significantly enriched gene sets from downregulated genes. Most of the enriched gene sets from upregulated genes were related to cell-cell signaling pathways. The most significantly enriched gene set from downregulated genes was the inflammatory response gene set. These findings show that therapeutic ultrasound influences cellular behavior in chronic wounds as early as 1 week after application. Considering the well-known role of chronic inflammation in impairing wound healing in chronic wounds, these results suggest that a downregulation of inflammatory genes is a possible biological mechanism of ultrasound-mediated venous chronic wound healing. Such increased understanding may ultimately lead to the enhancement of ultrasound devices to accelerate chronic wound healing and increase patient quality of life.
Integrated clinicopathologic and molecular analysis of endometrial carcinoma: Prognostic impact of the new ESGO-ESTRO-ESP endometrial cancer risk classification and proposal of histopathologic algorithm for its implementation in clinical practice
Authors: de Biase Dario , Maloberti Thais , Corradini Angelo Gianluca , Rosini Francesca , Grillini Marco , Ruscelli Martina , Coluccelli Sara , Altimari Annalisa , Gruppioni Elisa , Sanza Viviana , Turchetti Daniela , Galuppi Andrea , Ferioli Martina , Giunchi Susanna , Dondi Giulia , Tesei Marco , Ravegnini Gloria , Abbati Francesca , Rubino Daniela , Zamagni Claudio , De Iaco Pierandrea , Santini Donatella , Ceccarelli Claudio , Perrone Anna Myriam , Tallini Giovanni , De Leo Antonio
Published: March 2023

Introduction

The European Society of Gynecologic Oncology/European Society of Radiation Therapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) committee recently proposed a new risk stratification system for endometrial carcinoma (EC) patients that incorporates clinicopathologic and molecular features. The aim of the study is to compare the new ESGO/ESTRO/ESP risk classification system with the previous 2016 recommendations, evaluating the impact of molecular classification and defining a new algorithm for selecting cases for molecular analysis to assign the appropriate risk class.

Methods

The cohort included 211 consecutive EC patients. Immunohistochemistry and next-generation sequencing were used to assign molecular subgroups of EC: POLE mutant (POLE), mismatch repair deficient (MMRd), p53 mutant (p53abn), and no specific molecular profile (NSMP).

Results

Immuno-molecular analysis was successful in all cases, identifying the four molecular subgroups: 7.6% POLE, 32.2% MMRd, 20.9% p53abn, and 39.3% NSMP. The recent 2020 guidelines showed a 32.7% risk group change compared with the previous 2016 classification system: the reassignment is due to POLE mutations, abnormal p53 expression, and a better definition of lymphovascular space invasion. The 2020 system assigns more patients to lower-risk groups (42.2%) than the 2016 recommendation (25.6%). Considering the 2020 risk classification system that includes the difference between “unknown molecular classification” and “known,” the integration of molecular subgroups allowed 6.6% of patients to be recategorized into a different risk class. In addition, the use of the proposed algorithm based on histopathologic parameters would have resulted in a 62.6% reduction in molecular analysis, compared to applying molecular classification to all patients.

Conclusion

Application of the new 2020 risk classification integrating clinicopathologic and molecular parameters provided more accurate identification of low-and high-risk patients, potentially allowing a more specific selection of patients for post-operative adjuvant therapy. The proposed histopathologic algorithm significantly decreases the number of tests needed and could be a promising tool for cost reduction without compromising prognostic stratification.
A Proterozoic microbial origin of extant cyanide-hydrolyzing enzyme diversity
Authors: Schwartz Sarah L. , Rangel L. Thiberio , Payette Jack G. , Fournier Gregory P.
Published: March 2023

In addition to its role as a toxic environmental contaminant, cyanide has been hypothesized to play a key role in prebiotic chemistry and early biogeochemical evolution. While cyanide-hydrolyzing enzymes have been studied and engineered for bioremediation, the extant diversity of these enzymes remains underexplored. Additionally, the age and evolution of microbial cyanide metabolisms is poorly constrained. Here we provide comprehensive phylogenetic and molecular clock analyses of the distribution and evolution of the Class I nitrilases, thiocyanate hydrolases, and nitrile hydratases. Molecular clock analyses indicate that bacterial cyanide-reducing nitrilases were present by the Paleo- to Mesoproterozoic, and were subsequently horizontally transferred into eukaryotes. These results present a broad diversity of microbial enzymes that could be optimized for cyanide bioremediation.
Machine learning approach combined with causal relationship inferring unlocks the shared pathomechanism between COVID-19 and acute myocardial infarction
Authors: Liu Ying , Zhou Shujing , Wang Longbin , Xu Ming , Huang Xufeng , Li Zhengrui , Hajdu Andras , Zhang Ling
Published: March 2023

Background

Increasing evidence suggests that people with Coronavirus Disease 2019 (COVID-19) have a much higher prevalence of Acute Myocardial Infarction (AMI) than the general population. However, the underlying mechanism is not yet comprehended. Therefore, our study aims to explore the potential secret behind this complication.

Materials and methods

The gene expression profiles of COVID-19 and AMI were acquired from the Gene Expression Omnibus (GEO) database. After identifying the differentially expressed genes (DEGs) shared by COVID-19 and AMI, we conducted a series of bioinformatics analytics to enhance our understanding of this issue.

Results

Overall, 61 common DEGs were filtered out, based on which we established a powerful diagnostic predictor through 20 mainstream machine-learning algorithms, by utilizing which we could estimate if there is any risk in a specific COVID-19 patient to develop AMI. Moreover, we explored their shared implications of immunology. Most remarkably, through the Bayesian network, we inferred the causal relationships of the essential biological processes through which the underlying mechanism of co-pathogenesis between COVID-19 and AMI was identified.

Conclusion

For the first time, the approach of causal relationship inferring was applied to analyzing shared pathomechanism between two relevant diseases, COVID-19 and AMI. Our findings showcase a novel mechanistic insight into COVID-19 and AMI, which may benefit future preventive, personalized, and precision medicine.

Graphical abstract
Actinobacteria from Arctic and Atlantic deep-sea sediments—Biodiversity and bioactive potential
Authors: Ribeiro Inês , Antunes Jorge T. , Alexandrino Diogo A. M. , Tomasino Maria Paola , Almeida Eduarda , Hilário Ana , Urbatzka Ralph , Leão Pedro N. , Mucha Ana P. , Carvalho Maria F.
Published: March 2023

The deep-sea covers over 70% of the Earth’s surface and harbors predominantly uncharacterized bacterial communities. Actinobacteria are the major prokaryotic source of bioactive natural products that find their way into drug discovery programs, and the deep-sea is a promising source of biotechnologically relevant actinobacteria. Previous studies on actinobacteria in deep-sea sediments were either regionally restricted or did not combine a community characterization with the analysis of their bioactive potential. Here we characterized the actinobacterial communities of upper layers of deep-sea sediments from the Arctic and the Atlantic (Azores and Madeira) ocean basins, employing 16S rRNA metabarcoding, and studied the biosynthetic potential of cultivable actinobacteria retrieved from those samples. Metabarcoding analysis showed that the actinobacterial composition varied between the sampled regions, with higher abundance in the Arctic samples but higher diversity in the Atlantic ones. Twenty actinobacterial genera were detected using metabarcoding, as a culture-independent method, while culture-dependent methods only allowed the identification of nine genera. Isolation of actinobacteria resulted on the retrieval of 44 isolates, mainly associated with Brachybacterium, Microbacterium, and Brevibacterium genera. Some of these isolates were only identified on a specific sampled region. Chemical extracts of the actinobacterial isolates were subsequently screened for their antimicrobial, anticancer and anti-inflammatory activities. Extracts from two Streptomyces strains demonstrated activity against Candida albicans. Additionally, eight extracts (obtained from Brachybacterium, Brevibacterium, Microbacterium, Rhodococcus, and Streptomyces isolates) showed significant activity against at least one of the tested cancer cell lines (HepG2 and T-47D). Furthermore, 15 actinobacterial extracts showed anti-inflammatory potential in the RAW 264.4 cell model assay, with no concomitant cytotoxic response. Dereplication and molecular networking analysis of the bioactive actinobacterial extracts showed the presence of some metabolites associated with known natural products, but one of the analyzed clusters did not show any match with the natural products described as responsible for these bioactivities. Overall, we were able to recover taxonomically diverse actinobacteria with different bioactivities from the studied deep-sea samples. The conjugation of culture-dependent and -independent methods allows a better understanding of the actinobacterial diversity of deep-sea environments, which is important for the optimization of approaches to obtain novel chemically-rich isolates.
Enhanced bioremediation of triclocarban-contaminated soil by Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 immobilized on biochar and microbial community response
Authors: Miao Lei , Chen Siyuan , Yang Hua , Hong Yaqi , Sun Liwen , Yang Jie , Sun Guanjun , Liu Yi , Li Chunyan , Zang Hailian , Cheng Yi
Published: March 2023

Triclocarban (TCC), an emerging organic contaminant (EOC), has become a severe threat to soil microbial communities and ecological security. Here, the TCC-degrading strain Rhodococcus rhodochrous BX2 and DCA-degrading strain Pseudomonas sp. LY-1 (together referred to as TC1) were immobilized on biochar to remove TCC and its intermediates in TCC-contaminated soil. High-throughput sequencing was used to investigate the microbial community structure in TCC-contaminated soil. Analysis of co-occurrence networks was used to explore the mutual relationships among soil microbiome members. The results showed that the immobilized TC1 significantly increased the removal efficiency of TCC from 84.7 to 92.7% compared to CK (no TC1 cells on biochar) in 10 mg/L TCC liquid medium. The utilization of immobilized TC1 also significantly accelerated the removal of TCC from contaminated soil. Microbial community analysis revealed the crucial microorganisms and their functional enzymes participating in TCC degradation in soil. Moreover, the internal labor division patterns and connections of TCC-degrading microbes, with a focus on strains BX2 and LY-1, were unraveled by co-occurrence networks analysis. This work provides a promising strategy to facilitate the bioremediation of TCC in soil, which has potential application value for sustainable biobased economies.
Clostridioides difficile minimal nutrient requirements for flagellar motility
Authors: Schwanbeck Julian , Oehmig Ines , Groß Uwe , Bohne Wolfgang
Published: March 2023

As many gastro-intestinal pathogens, the majority of Clostridioides difficile strains express flagella together with a complete chemotaxis system. The resulting swimming motility is likely contributing to the colonization success of this important pathogen. In contrast to the well investigated general energy metabolism of C. difficile, little is known about the metabolic requirements for maintaining the ion motive force across the membrane, which in turn powers the flagellar motor. We studied here systematically the effect of various amino acids and carbohydrates on the swimming velocity of C. difficile using video microscopy in conjunction with a software based quantification of the swimming speed. Removal of individual amino acids from the medium identified proline and cysteine as the most important amino acids that power swimming motility. Glycine, which is as proline one of the few amino acids that are reduced in Stickland reactions, was not critical for swimming motility. This suggests that the ion motive force that powers the flagellar motor, is critically depending on proline reduction. A maximal and stable swimming motility was achieved with only four compounds, including the amino acids proline, cysteine and isoleucine together with a single, but interchangeable carbohydrate source such as glucose, succinate, mannose, ribose, pyruvate, trehalose, or ethanolamine. We expect that the identified “minimal motility medium” will be useful in future investigations on the flagellar motility and chemotactic behavior in C. difficile, particularly for the unambiguous identification of chemoattractants.