bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning together: The dynamics of training teachers for disability inclusion in South Africa
Authors: Nseibo Kofi , Vergunst Richard , McKenzie Judith , Kelly Jane , Karisa Amani , Watermeyer Brian
Published: October 2022

Despite the need for inclusive education in South Africa, many teachers have not been appropriately trained for the inclusion process for learners with disabilities in classrooms. A consideration of teacher education for inclusive education involves examining both the structural and professional barriers to training that prevent effective implementation. We review the outcomes of a teacher education project in South Africa through three studies that emanate from Teacher Empowerment for Disability Inclusion (TEDI) at the University of Cape Town. These studies are a situation analysis; a survey of teacher education availability for working with learners with severe disabilities; and an evaluation of short courses. We draw on these studies to develop a holistic picture of the kind of training needed to develop the knowledge, attitudes and skills of teachers to address barriers to learning that arise from disability. This entails a conceptual analysis of how the different elements of training work together to address learner needs.
The impact of BMI on long-term anthropometric and metabolic outcomes in girls with idiopathic central precocious puberty treated with GnRHas
Authors: Bruzzi Patrizia , Valeri Lara , Sandoni Marcello , Madeo Simona Filomena , Predieri Barbara , Lucaccioni Laura , Iughetti Lorenzo
Published: October 2022

Background

Gonadotropin-releasing hormone analogs (GnRHas) are effective in increasing the final height of children with idiopathic central precocious puberty (ICPP). However, in previous years, some transient metabolic complications have been described during this treatment, for which there are no long-term outcome data. Our study aimed to evaluate the efficacy of GnRHas and clarify if body mass index (BMI) at diagnosis of ICPP could influence long-term outcomes.

Methods

This was an observational, retrospective study that recruited a cohort of girls with ICPP. Data for anthropometric measures, fasting lipid profile, and glucose metabolism were collected at baseline [when GnRHas treatment started (T1)], at the end of the treatment (T2), and near-final height (nFH) or final height (FH) (T3). Predicted adult height (PAH) was calculated at T1 following Bayley and Pinneau’s method. Analysis was carried out using BMI standard deviation score (SDS) categories at T1 (group A, normal weight, vs. group B, overweight/obese).

Results

Fifty-seven girls with ICPP who were treated with GnRHas were enrolled in the study (group A vs. group B: 33 vs. 24 patients, aged 7.86 ± 0.81 vs. 7.06 ± 1.61 years, respectively; p < 0.05). In the study population, nFH/FH was in line with the target height (TH) (p = 0.54), with a mean absolute height gain of 11.82 ± 5.35 cm compared with PAH. Even if the length of therapy was shorter (group A vs. group B: 1.84 ± 2.15 vs. 2.10 ± 0.81 years, respectively; p < 0.05) and the age at menarche was younger (group A vs. group B: 10.56 ± 1.01 vs. 11.44 ± 0.85 years, respectively; p < 0.05) in group B than in group A, the nFH/FH gain was still comparable between the two groups (p = 0.95). At nFH/FH, BMI SDS was still greater in group B than in group A (p = 0.012), despite the fact that BMI SDS significantly increased in group A only (p < 0.05). Glucose metabolism got worst during GnRHa with a complete restoring after it, independently from pre-treatment BMI. The ratio of low-density to high-density lipoprotein cholesterol transiently deteriorated during treatment with GnRHas in group A only (p = 0.030).

Conclusions

Our results confirm the effectiveness of treatment with GnRHas on growth and do not support the concern that being overweight and obese can impair the long-term outcomes of GnRHas therapy. However, the observed transient impairment of metabolic parameters during treatment suggests that clinicians should encourage ICPP girls treated with GnRHas to have a healthy lifestyle, regardless of their pretreatment BMI.
Recent advances in the solar thermochemical splitting of carbon dioxide into synthetic fuels
Authors: Rony Zahidul Islam , Mofijur M. , Ahmed Shams Forruque , Kabir Zobaidul , Chowdhury Ashfaque Ahmed , Almomani Fares
Published: October 2022

Recent years have seen a sharp rise in CO2 emissions into the atmosphere, which has contributed to the issue of global warming. In response to this several technologies have been developed to convert CO2 into fuel. It is discovered that the employment of a solar-driven thermochemical process (S-DTCP) that transforms CO2 into fuels can increase the efficiency of the production of sustainable fuels. The process involves the reduction of metal oxide (MO) and oxidizing it with CO2 in a two-step process using concentrated solar power (CSP) at higher and lower temperatures, respectively. This study summarizes current advancements in CO2 conversion methods based on MO thermochemical cycles (ThCy), including their operating parameters, types of cycles, and working principles. It was revealed that the efficiency of the solar conversion of CO2 to fuel is not only influenced by the composition of the MO, but also by its morphology as well as the available surface area for solid/gas reactions and the diffusion length. The conversion mechanism is governed by surface reaction, which is influenced by these two parameters (diffusion length and specific surface area). Solar energy contributes to the reduction and oxidation steps by promoting reaction kinetics and heat and mass transport in the material. The information on recent advances in metal oxide-based carbon dioxide conversion into fuels will be beneficial to both the industrial and academic sectors of the economy.
Green HR practices and environmental performance: The mediating mechanism of employee outcomes and moderating role of environmental values
Authors: Adeel Muhammad , Mahmood Shahid , Khan Kanwal Iqbal , Saleem Saima
Published: October 2022

Scholars focused on behavioral changes in employees rather than depending solely on technology enhancements due to organizations’ poor and inefficient environmental performance. The purpose of this research is to observe the influence of green HR practices (GHRP) on work engagement and job satisfaction in the environment and its effect on the environmental performance of universities. Furthermore, the mediating effect of work engagement and job satisfaction and moderating impact of environmental values are explored. The data were collected from 337 officials and faculty members of universities of Pakistan through structured questionnaires. The SPSS process macros results indicate that GHRP significantly impacts environmental performance, job satisfaction, and work engagement. The mediation results reveal that work engagement and job satisfaction acted as a means by which GHRP of universities can positively affect environmental performance. The moderation results reveal that environmental values strengthen the relation of GHRP with environmental performance. The study highlights the significance and importance of GHRP for environmental performance and extends the literature by shedding light on the role of employee outcomes and environmental values.
Assessment of catalytic thermal hydrolysis of swine manure slurry as liquid fertilizer: Insights into nutrients and metals
Authors: Xie Shiyu , Zhang Tao , Mishra Anshuman , Tiwari Ashutosh , Bolan Nanthi S.
Published: October 2022

The recovery of nutrients from livestock manure has generated a lot of interest in biosolids value-adding. There is now more research on manure with high solids content but less study on manure with lower solids content. This study used swine manure slurry as the research object and comprehensively examined the characteristics of organic matter conversion, nitrogen, phosphorus, and metals release during the catalytic-thermal hydrolysis (TH) process. It was found that ammonia nitrogen showed a continuous increase with increasing temperature while inorganic phosphorus showed a rising and then decreasing trend. The addition of HCl and H2O2 (TH-HCl-H2O2) promoted the hydrolysis of organic matter, showing the best nitrogen and phosphorus release performance, releasing 62.2% of inorganic phosphorus and 50.8% of nitrogen. The release characteristics of nutrients and metals from the TH process were significantly affected by the addition of HCl and H2O2, according to structural equation modelling study. The data analysis demonstrated that the liquid fertilizer produced by TH did not surpass the environmental risk associated with nutrients or the ecological risk associated with heavy metals. This study would offer theoretical justification for biowaste conversion for agricultural applications.
Spatial correlations and driving mechanisms of low-carbon agricultural development in china
Authors: Fang Fang , Zhao Jun , Di Jie , Zhang Lijie
Published: October 2022

Low-carbon agricultural development in China is a prerequisite for rural revitalization and a key to achieving socio-economic green transformation. This paper used agricultural data from 30 Chinese provinces from 2001 to 2020, considering both carbon emissions from farming and livestock, agricultural low-carbon total factor productivity (ALTFP) was measured using the RSBM-GML index. Based on this, the network characteristics and driving mechanisms of low-carbon synergistic development in agriculture were explored with the help of an improved gravity model and social network analysis, and the dominant provinces in low-carbon synergistic development in agriculture are identified. The study revealed that the spatially linked network of ALTFP in China exhibits multi-threaded characteristics of spillover to non-adjacent provinces, and the whole network has a sparse structure and hierarchy. The eastern regions such as Beijing, Tianjin, Shanghai, Jiangsu, and Zhejiang are at the core of the network, with closer ties to other regions and a stronger role in allocating resources. While the western regions such as Xinjiang, Qinghai, and Gansu are located at the periphery of the network, with weaker access to the resources. Meanwhile, the spatial proximity of provinces, the widening of differences in urbanization levels and differences in financial support for agriculture, and the narrowing of differences in the educational attainment of rural labor have significantly contributed to the formation of provincial spatial linkages. This study reveals that China’s government needs to give full play to the role of core regions as “leaders”, and promote the balanced and coordinated regional development of low-carbon agriculture in China. In addition, policy makers should further optimize the spatial allocation of agricultural resource elements between provinces. The findings of the study provide reference suggestions for the development of regionally differentiated agricultural low-carbon development plans.
Museomics and the holotype of a critically endangered cricetid rodent provide key evidence of an undescribed genus
Authors: Castañeda-Rico Susette , Edwards Cody W. , Hawkins Melissa T. R. , Maldonado Jesús E.
Published: October 2022

Historical DNA obtained from voucher specimens housed in natural history museums worldwide have allowed the study of elusive, rare or even extinct species that in many cases are solely represented by museum holdings. This has resulted in the increase of taxonomic representation of many taxa, has led to the discovery of new species, and has yielded stunning novel insights into the evolutionary history of cryptic or even undescribed species. Peromyscus mekisturus, is a critically endangered cricetid rodent endemic to Mexico and is only known from two museum specimens collected in 1898 and 1947. Intensive field work efforts to attempt to determine if viable populations still exist have failed, suggesting that this species is extinct or is nearing extinction. In addition, a recent study using mitogenomes demonstrated that P. mekisturus forms a well-supported clade outside the genus Peromyscus and hypothesized that this taxon is the sister group of the genus Reithrodontomys. Here, we used target enrichment and high-throughput sequencing of several thousand nuclear ultraconserved elements and mitogenomes to reconstruct dated phylogenies to test the previous phylogenetic hypothesis. We analyzed the holotype and the only other known specimen of P. mekisturus and museum samples from other peromyscine rodents to test the phylogenetic position of the species. Our results confirm that the only two specimens known to science of P. mekisturus belong to the same species and support the hypothesis that this species belongs to an undescribed genus of cricetid rodents that is sister to the genus Reithrodontomys. We dated the origin of P. mekisturus together with other speciation events in peromyscines during the late Pliocene – early Pleistocene and related these events with the Pleistocene climatic cycles. In light of our results, we recommend a taxonomic re-evaluation of this enigmatic species to properly recognize its taxonomic status as a new genus. We also acknowledge the relevance of generating genomic data from type specimens and highlight the need and importance of continuing to build the scientific heritage of the collections to study and better understand past, present, and future biodiversity.
Macrophage-related molecular subtypes in lung adenocarcinoma identify novel tumor microenvironment with prognostic and therapeutic implications
Authors: Wen Heng , Chen Hanjian , Xie Liwei , Li Zetao , Zhang Qian , Tian Qiping
Published: October 2022

Background: Lung adenocarcinoma (LUAD) is a life-threatening malignant tumor, contributing for the largest cancer burden worldwide. Tumor microenvironment (TME) is composed of various immune cells, stromal cells and tumor cells, which is highly associated with the cancer prognosis and the response to immunotherapy, in which macrophages in TME have been revealing a potential target for cancer treatment. In this study, we sought to further explore the role of macrophages in LUAD progression and establish a risk model related to macrophages for LUAD.

Methods: We explored immune-related pathways that might be affected by counting positively associated genes in macrophages. Molecular typing was also constructed by mining macrophage-associated genes with prognostic value through COX regression and other analyses. RiskScore prognostic models were constructed using lasso regression and stepwise multifactorial regression analysis. The differences on clinical characteristics among three subtypes (C1, C2, and C3) and RiskScore subtypes were analyzed in TCGA dataset. Immunological algorithms such as TIMER, ssGSEA, MCP-Counter, ESTIMATE, and TIDE were used to calculate the level of difference in immune infiltration between the different subtypes. The TCGA mutation dataset processed by mutect2 was used to demonstrate the frequency of mutations between different molecular subtypes. Finally, nomograms, calibration curves, and decision curves were created to assess the predictive accuracy and reliability of the model.

Results: The C1 subtype demonstrated the best prognostic outcome, accompanied by higher levels of immune infiltration and lower mutation frequency, while the majority of patients in the C1 subtype were women under 65 years of age. Myeloid-derived suppressor cell (MDSC) scores were higher in the C3 subtype, suggesting a more severe immune escape, which may have contributed to the tumor evading the immune system resulting in a poorer prognosis for patients. In addition, our RiskScore prognostic model had good predictive accuracy and reliability.

Conclusion: This paper provides a study of macrophage-related pathways, immunosuppression, and their mechanisms of action in lung cancer, along with targets for future treatment to guide the optimal treatment of lung cancer.
Construction and validation of a prognostic marker and risk model for HCC ultrasound therapy combined with WGCNA identification
Authors: Bi Yunlong , Jing Yu , Guo Lingling
Published: October 2022

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with a highly aggressive and metastatic nature. Ultrasound remains a routine monitoring tool for screening, treatment and post-treatment recheck of HCC. Therefore, it is of great significance to explore the role of ultrasound therapy and related genes in prognosis prediction and clinical diagnosis and treatment of HCC.

Methods: Gene co-expression networks were developed utilizing the R package WGCNA as per the expression profiles and clinical features of TCGA HCC samples, key modules were identified by the correlation coefficients between clinical features and modules, and hub genes of modules were determined as per the GS and MM values. Ultrasound treatment differential expression genes were identified using R package limma, and univariate Cox analysis was conducted on the intersection genes of ultrasound differential expression genes and hub genes of key HCC modules to screen the signatures linked with HCC prognosis and construct a risk model. The median risk score was used as the threshold point to classify tumor samples into high- and low-risk groups, and the R package IOBR was used to assess the proportion of immune cells in high- and low-risk groups, R package maftools to assess the genomic mutation differences in high- and low-risk groups, R package GSVA’s ssgsea algorithm to assess the HALLMARK pathway enrichment analysis, and R package pRRophetic to analyze drug sensitivity in patients with HCC.

Results: WGCNA analysis based on the expression profiles and clinical data of the TCGA LIHC cohort identified three key modules with two major clinical features associated with HCC. The intersection of ultrasound-related differential genes and module hub genes was selected for univariate Cox analysis to identify prognostic factors significantly associated with HCC, and a risk score model consisting of six signatures was finally developed to analyze the prognosis of individuals with HCC. The risk model showed strength in the training set, overall set, and external validation set. The percentage of immune cell infiltration, genomic mutations, pathway enrichment scores, and chemotherapy drug resistance were significantly different between high- and low-risk groups according to the risk scores. Expression of model genes correlated with tumor immune microenvironment and clinical tumor characteristics while generally differentially expressed in pan-cancer tumor and healthy samples. In the immunotherapy dataset, patients in the high-risk group had a worse prognosis with immunotherapy, indicating that subjects in the low-risk group are more responsive to immunotherapy.

Conclusion: The 6-gene signature constructed by ultrasound treatment of HCC combined with WGCNA analysis can be used for prognosis prediction of HCC patients and may become a marker for immune response.
Comparative and evolutionary analysis of RIP kinases in immune responses
Authors: Lv Shangge , Jiang Yu , Li Yuzheng , Huang Ruilin , Peng Lingyu , Ma Zhaoyin , Lu Nan , Lin Xiaoying , Yan Jie
Published: October 2022

The group of receptor-interacting protein (RIP) kinases has seven members (RIPK1–7), with one homologous kinase domain but distinct non-kinase regions. Although RIPK1–3 have emerged as key modulators of inflammation and cell death, few studies have connected RIPK4–7 to immune responses. The divergence in domain structures and paralogue information in the Ensembl database have raised question about the phylogeny of RIPK1–7. In this study, phylogenetic trees of RIPK1–7 and paralogues constructed using full-length amino acid sequences or Kinase domain demonstrate that RIPK6 and RIPK7 are distinct from RIPK1–5 and paralogues shown in the Ensembl database are inaccurate. Comparative and evolutionary analyses were subsequently performed to gain new clues about the potential functions of RIPK3–7. RIPK3 gene loss in birds and animals that undergo torpor, a common physiological phenomenon in cold environments, implies that RIPK3 may be involved in ischemia-reperfusion injury and/or high metabolic rate. The negligible expression of RIPK4 and RIPK5 in immune cells is likely responsible for the lack of studies on the direct role of these members in immunity; RIPK6 and RIPK7 are conserved among plants, invertebrates and vertebrates, and dominantly expressed in innate immune cells, indicating their roles in innate immunity. Overall, our results provide insights into the multifaceted and conserved biochemical functions of RIP kinases.
Genome-wide analysis identified candidate variants and genes associated with heat stress adaptation in Egyptian sheep breeds
Authors: Aboul-Naga Adel M. , Alsamman Alsamman M. , El Allali Achraf , Elshafie Mohmed H. , Abdelal Ehab S. , Abdelkhalek Tarek M. , Abdelsabour Taha H. , Mohamed Layaly G. , Hamwieh Aladdin
Published: October 2022

Heat stress caused by climatic changes is one of the most significant stresses on livestock in hot and dry areas. It has particularly adverse effects on the ability of the breed to maintain homeothermy. Developing countries are advised to protect and prepare their animal resources in the face of potential threats such as climate change. The current study was conducted in Egypt’s three hot and dry agro-ecological zones. Three local sheep breeds (Saidi, Wahati, and Barki) were studied with a total of 206 ewes. The animals were exercised under natural heat stress. The heat tolerance index of the animals was calculated to identify animals with high and low heat tolerance based on their response to meteorological and physiological parameters. Genomic variation in these breeds was assessed using 64,756 single nucleotide polymorphic markers (SNPs). From the perspective of comparative adaptability to harsh conditions, our objective was to investigate the genomic structure that might control the adaptability of local sheep breeds to environmental stress under hot and dry conditions. In addition, indices of population structure and diversity of local breeds were examined. Measures of genetic diversity showed a significant influence of breed and location on populations. The standardized index of association (rbarD) ranged from 0.0012 (Dakhla) to 0.026 (Assuit), while for the breed, they ranged from 0.004 (Wahati) to 0.0103 (Saidi). The index of association analysis (Ia) ranged from 1.42 (Dakhla) to 35.88 (Assuit) by location and from 6.58 (Wahati) to 15.36 (Saidi) by breed. The most significant SNPs associated with heat tolerance were found in the MYO5A, PRKG1, GSTCD, and RTN1 genes (p ≤ 0.0001). MYO5A produces a protein widely distributed in the melanin-producing neural crest of the skin. Genetic association between genetic and phenotypic variations showed that OAR1_18300122.1, located in ST3GAL3, had the greatest positive effect on heat tolerance. Genome-wide association analysis identified SNPs associated with heat tolerance in the PLCB1, STEAP3, KSR2, UNC13C, PEBP4, and GPAT2 genes.
From multitude to singularity: An up-to-date overview of scRNA-seq data generation and analysis
Authors: Carangelo Giulia , Magi Alberto , Semeraro Roberto
Published: October 2022

Single cell RNA sequencing (scRNA-seq) is today a common and powerful technology in biomedical research settings, allowing to profile the whole transcriptome of a very large number of individual cells and reveal the heterogeneity of complex clinical samples. Traditionally, cells have been classified by their morphology or by expression of certain proteins in functionally distinct settings. The advent of next generation sequencing (NGS) technologies paved the way for the detection and quantitative analysis of cellular content. In this context, transcriptome quantification techniques made their advent, starting from the bulk RNA sequencing, unable to dissect the heterogeneity of a sample, and moving to the first single cell techniques capable of analyzing a small number of cells (1–100), arriving at the current single cell techniques able to generate hundreds of thousands of cells. As experimental protocols have improved rapidly, computational workflows for processing the data have also been refined, opening up to novel methods capable of scaling computational times more favorably with the dataset size and making scRNA-seq much better suited for biomedical research. In this perspective, we will highlight the key technological and computational developments which have enabled the analysis of this growing data, making the scRNA-seq a handy tool in clinical applications.
Tristetraprolin limits age-related expansion of myeloid-derived suppressor cells
Authors: Kwack Kyu Hwan , Zhang Lixia , Kramer Elliot D. , Thiyagarajan Ramkumar , Lamb Natalie A. , Arao Yukitomo , Bard Jonathan E. , Seldeen Kenneth L. , Troen Bruce R. , Blackshear Perry J. , Abrams Scott I. , Kirkwood Keith L.
Published: October 2022

Aging results in enhanced myelopoiesis, which is associated with an increased prevalence of myeloid leukemias and the production of myeloid-derived suppressor cells (MDSCs). Tristetraprolin (TTP) is an RNA binding protein that regulates immune-related cytokines and chemokines by destabilizing target mRNAs. As TTP expression is known to decrease with age in myeloid cells, we used TTP-deficient (TTPKO) mice to model aged mice to study TTP regulation in age-related myelopoiesis. Both TTPKO and myeloid-specific TTPKO (cTTPKO) mice had significant increases in both MDSC subpopulations M-MDSCs (CD11b+Ly6ChiLy6G-) and PMN-MDSCs (CD11b+Ly6CloLy6G+), as well as macrophages (CD11b+F4/80+) in the spleen and mesenteric lymph nodes; however, no quantitative changes in MDSCs were observed in the bone marrow. In contrast, gain-of-function TTP knock-in (TTPKI) mice had no change in MDSCs compared with control mice. Within the bone marrow, total granulocyte-monocyte progenitors (GMPs) and monocyte progenitors (MPs), direct antecedents of M-MDSCs, were significantly increased in both cTTPKO and TTPKO mice, but granulocyte progenitors (GPs) were significantly increased only in TTPKO mice. Transcriptomic analysis of the bone marrow myeloid cell populations revealed that the expression of CC chemokine receptor 2 (CCR2), which plays a key role in monocyte mobilization to inflammatory sites, was dramatically increased in both cTTPKO and TTPKO mice. Concurrently, the concentration of CC chemokine ligand 2 (CCL2), a major ligand of CCR2, was high in the serum of cTTPKO and TTPKO mice, suggesting that TTP impacts the mobilization of M-MDSCs from the bone marrow to inflammatory sites during agingviaregulation of the CCR2-CCL2 axis. Collectively, these studies demonstrate a previously unrecognized role for TTP in regulating age-associated myelopoiesis through the expansion of specific myeloid progenitors and M-MDSCs and their recruitment to sites of injury, inflammation, or other pathologic perturbations.
A randomized clinical trial to stimulate the cholinergic anti-inflammatory pathway in patients with moderate COVID-19-pneumonia using a slow-paced breathing technique
Authors: Balint Elisabeth Maria , Grüner Beate , Haase Sophia , Kaw-Geppert Mandakini , Thayer Julian F. , Gündel Harald , Jarczok Marc N.
Published: October 2022

Purpose

A characteristic problem occurring in COVID-19 is excessive elevations of pro-inflammatory cytokines (e.g. IL-6 and CRP) which are associated with worse clinical outcomes. Stimulation of the vagally-mediated cholinergic anti-inflammatory reflex by slow paced breathing with prolonged exhalation may present a clinically relevant way to reduce circulating IL-6.

Method

Single-center randomized controlled clinical trial with enrolment of 46 patients hospitalized with confirmed severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (primary diagnosis). Differences between intervention (4sec inhalation, 6sec exhalation for 20 minutes 3x daily) and control group in IL-6 calculated using multilevel mixed-effect linear regression models with random slope including the covariates relevant comorbidities, COVID-19 medication, and age. Both groups received standard care.

Results

Mean age was 57 years ± 13 years, N= 28 (60%) male, N=30 (65%) with relevant comorbidities. The model including group-by-time interaction revealed a significantly lower trajectory of IL-6 in the intervention group (effect size Cohens f2 = 0.11, LR-test p=.040) in the intention-to-treat sample, confirmed by per-protocol analysis (f2 = 0.15, LR-test p=.022). Exploratory analysis using the median split of practice time to predict IL-6 of the next morning indicated a dose-response relationship with beneficial effects of practice time above 45 minutes per day. Oxygen saturation remained unchanged during slow-paced breathing (95.1% ± 2.1% to 95.4% ± 1.6%).

Conclusion

Patients practicing slow-paced breathing had significantly lower IL-6 values than controls with a small to medium effect size and without relevant side effects. Further trials should evaluate clinical outcomes and an earlier start of the intervention. Slow-paced breathing could be an easy to implement, low-cost, safe and feasible adjuvant therapeutic approach to reduce circulating IL-6 in moderate COVID-19 pneumonia.

Clinical Trial Registration

https://www.drks.de, identifier DRKS00023971, Universal Trial Number (UTN) U1111-1263-8658.
CD18 controls the development and activation of monocyte-to-macrophage axis during chronic schistosomiasis
Authors: Souza Camila O. S. , Elias-Oliveira Jefferson , Pastore Marcella R. , Fontanari Caroline , Rodrigues Vanessa F. , Rodriguez Vanderlei , Gardinassi Luiz G. , Faccioli Lúcia H.
Published: October 2022

Schistosomiasis is a neglected tropical disease caused by worms of the genusSchistosomaspp. The progression of disease results in intense tissue fibrosis and high mortality rate. After egg deposition by adult worms, the inflammatory response is characterized by the robust activation of type 2 immunity. Monocytes and macrophages play critical roles during schistosomiasis. Inflammatory Ly6Chighmonocytes are recruited from the blood to the inflammatory foci and differentiate into alternatively activated macrophages (AAMs), which promote tissue repair. The common chain of β2-integrins (CD18) regulates monocytopoiesis and mediates resistance to experimental schistosomiasis. There is still limited knowledge about mechanisms controlled by CD18 that impact monocyte development and effector cells such as macrophages during schistosomiasis. Here, we show thatCD18lowmice chronically infected withS. mansonidisplay monocyte progenitors with reduced proliferative capacity, resulting in the accumulation of the progenitor cell denominated proliferating-monocyte (pMo). Consequently, inflammatory Ly6Chighand patrolling Ly6Clowmonocytes are reduced in the bone marrow and blood. Mechanistically, low CD18 expression decreasesIrf8gene expression in pMo progenitor cells, whose encoded transcription factor regulates CSFR1 (CD115) expression on the cell surface. Furthermore, low CD18 expression affects the accumulation of inflammatory Ly6ChighCD11b+monocytes in the liver while the adoptive transference of these cells to infected-CD18lowmice reduced the inflammatory infiltrate and fibrosis in the liver. Importantly, expression ofIl4,Chil3l3andArg1was downregulated, CD206+PD-L2+AAMs were reduced and there were lower levels of IL-10 in the liver ofCD18lowmice chronically infected withS. mansoni. Overall, these findings suggest that CD18 controls the IRF8-CD115 axis on pMo progenitor cells, affecting their proliferation and maturation of monocytes. At the same time, CD18 is crucial for the appropriate polarization and function of AAMs and tissue repair during chronic schistosomiasis.
The white blood cell count to mean platelet volume ratio for ischemic stroke patients after intravenous thrombolysis
Authors: Weng Yiyun , Gao Yufan , Zhao Mingyue , Zeng Tian , Huang Jiaqi , Xie Haobo , Huang Jiexi , Chen Yiqun , Hu Xiaoya , Xu Jiahan , Zhu Jinrong , Lin Suichai , Ke Tingting , Li Xiang , Zhang Xu
Published: October 2022

Background and Purpose

White blood cell count to mean platelet volume ratio (WMR) is increasingly recognized as a promising biomarker. However, its predictive capability for acute ischemic stroke (AIS) patients is relatively less researched. The primary aim of this study is to explore its prognostic value in AIS patients after reperfusion regarding 3-month poor functional outcome.

Methods

A total of 549 AIS patients who had undergone vascular reperfusion procedure with complete 3-month follow-up were retrospectively recruited in this study. White blood cell count, mean platelet volume at 24 h of admission were recorded. Stroke severity had been estimated using the National Institutes of Health Stroke Scale (NIHSS) and poor outcome was defined as modified Rankin Scale (mRS) 3–6 at 3 months.

Results

AIS patients with poor functional outcome at 3 months displayed higher WMR. A positive correlation between WMR and NIHSS score was found (r = 0.334, p < 0.001). After adjusting potential confounders, WMR was still an independent risk factor for poor prognosis at 3 months (OR = 2.257, 95% CI [1.117-4.564], p = 0.023) in multivariate logistic regression model. Subgroup analyses further suggested a significant association between WMR and poor outcome in high baseline NIHSS (per 0.1-point increase: OR = 1.153, 95% CI [1.014-1.312], p = 0.030) group. Receiver operating characteristic (ROC) curves analysis was utilized to assess the predictive ability of WMR, indicating a cut-off value of 0.86. A nomogram that includes age, sex, NIHSS on admission, high WMR for predicting 1-year all-cause survival was also developed (C-index = 0.628).

Conclusions

WMR is significantly correlated with stroke severity on admission and is proved to be an important prognostic indicator for AIS outcomes, especially in high NIHSS on admission group. Additionally, the developed nomogram that includes high WMR for predicting 1-year survival provides us with an effective visualization tool.
Microbial communities associated with epilithic algal matrix with different morphological characters in Luhuitou fringing reef
Authors: Zhou Tiancheng , Hu Simin , Jia Nan , Zhang Chen , Huang Hui , Liu Sheng
Published: October 2022

The microbiota is an important component of the epilithic algal matrix (EAM) and plays a central role in the biogeochemical cycling of important nutrients in coral reef ecosystems. Insufficient studies on EAM microbiota diversity have led to a limited understanding of the ecological functions of EAMs in different states. To explore the microbial community of EAMs in the Luhuitou fringing reef in Sanya, China, which has undergone the incessant expansion and domination of algae over the past several decades, investigations were conducted in the reef’s intertidal zone. Five types of substrate habitats (dead branching coral, dead massive coral, dead flat coral, granite block, and concrete block) were selected, and their microbial communities were analyzed by high-throughput sequencing of EAM holobionts using the 16S rDNA V4 region. Proteobacteria was the most abundant group, accounting for more than 70% of reads of the microbial composition across all sites, followed by Cyanobacteria (15.89%) and Bacteroidetes (5.93%), respectively. Cluster analysis divided all microbial communities into three groups, namely short, medium, and long EAMs. Algal length was the most important morphological factor impacting the differences in the composition of the EAM microbiota. The three EAM groups had 52 common OTUs and 78.52% common sequences, among which the most abundant were Vibrio spp. and Photobacterium spp. The three types of EAM also had unique OTUs. The short EAMs had 238 unique OTUs and 48.61% unique sequences, mainly in the genera Shewanella and Cyanobacterium. The medium EAMs contained 130 unique OTUs and 4.36% unique sequences, mainly in the genera Pseudomonas and Bacillus. The long EAMs only had 27 unique OTUs and 4.13% unique sequences, mainly in the genus Marinobacter. Compared with short EAM, medium and long EAM had a lower proportion of autotrophic bacteria and higher proportion of potential pathogenic bacteria. It is suggested that EAMs with different phenotypes have different microbial compositions, and the ecological function of the EAM microbiota changes from autotrophic to pathogenic with an increase in algal length. As EAMs have expanded on coastal coral reefs worldwide, it is essential to comprehensively explore the community structure and ecological role of their microbial communities.
Livedoid vasculopathy – A diagnostic and therapeutic challenge
Authors: Burg Maria Rosa , Mitschang Carolin , Goerge Tobias , Schneider Stefan Werner
Published: October 2022

Livedoid vasculopathy is a rare, chronic-recurrent occlusive disorder in the microcirculation of dermal vessels. The clinical appearance is characterized by Livedo racemosa, painful ulceration, located in the distal parts of the lower extremities, followed by healing as porcelain-white, atrophic scars, the so-called Atrophie blanche. Different conditions that can promote a hypercoagulable state, such as inherited and acquired thrombophilias, autoimmune connective-tissue diseases and neoplasms, can be associated with livedoid vasculopathy. Therefore, livedoid vasculopathy is currently considered to be a coagulation disorder, clearly distinguished from inflammatory vasculitis. Although there are hints to hypercoaguability and secondary inflammation, pathophysiology is not completely understood. Diagnosis is made by synopsis of history, clinical and histopathological findings. Early and adequate therapy is essential to maintain life quality and avoid irreversible complications. Better understanding of molecular mechanisms is required to establish appropriate therapy regimens. This article presents the current state of knowledge about livedoid vasculopathy and proposes an algorithmic approach for diagnosis and therapy.
Development and validation of a predictive model combining clinical, radiomics, and deep transfer learning features for lymph node metastasis in early gastric cancer
Authors: Zeng Qingwen , Li Hong , Zhu Yanyan , Feng Zongfeng , Shu Xufeng , Wu Ahao , Luo Lianghua , Cao Yi , Tu Yi , Xiong Jianbo , Zhou Fuqing , Li Zhengrong
Published: October 2022

Background

This study aims to develop and validate a predictive model combining deep transfer learning, radiomics, and clinical features for lymph node metastasis (LNM) in early gastric cancer (EGC).

Materials and methods

This study retrospectively collected 555 patients with EGC, and randomly divided them into two cohorts with a ratio of 7:3 (training cohort, n = 388; internal validation cohort, n = 167). A total of 79 patients with EGC collected from the Second Affiliated Hospital of Soochow University were used as external validation cohort. Pre-trained deep learning networks were used to extract deep transfer learning (DTL) features, and radiomics features were extracted based on hand-crafted features. We employed the Spearman rank correlation test and least absolute shrinkage and selection operator regression for feature selection from the combined features of clinical, radiomics, and DTL features, and then, machine learning classification models including support vector machine, K-nearest neighbor, random decision forests (RF), and XGBoost were trained, and their performance by determining the area under the curve (AUC) were compared.

Results

We constructed eight pre-trained transfer learning networks and extracted DTL features, respectively. The results showed that 1,048 DTL features extracted based on the pre-trained Resnet152 network combined in the predictive model had the best performance in discriminating the LNM status of EGC, with an AUC of 0.901 (95% CI: 0.847–0.956) and 0.915 (95% CI: 0.850–0.981) in the internal validation and external validation cohorts, respectively.

Conclusion

We first utilized comprehensive multidimensional data based on deep transfer learning, radiomics, and clinical features with a good predictive ability for discriminating the LNM status in EGC, which could provide favorable information when choosing therapy options for individuals with EGC.
Genetics in parkinson’s disease: From better disease understanding to machine learning based precision medicine
Authors: Aborageh Mohamed , Krawitz Peter , Fröhlich Holger
Published: October 2022

Parkinson’s Disease (PD) is a neurodegenerative disorder with highly heterogeneous phenotypes. Accordingly, it has been challenging to robustly identify genetic factors associated with disease risk, prognosis and therapy response via genome-wide association studies (GWAS). In this review we first provide an overview of existing statistical methods to detect associations between genetic variants and the disease phenotypes in existing PD GWAS. Secondly, we discuss the potential of machine learning approaches to better quantify disease phenotypes and to move beyond disease understanding towards a better-personalized treatment of the disease.
Insights into the binding mode of AS1411 aptamer to nucleolin
Authors: Bie Lihua , Wang Yue , Jiang Fuze , Xiao Zhen , Zhang Lianjun , Wang Jing
Published: October 2022

AS1411 aptamer can function as a recognition probe to detect the cell surface nucleolin overexpressed in cancer cells, however, little is known about their binding process. This study proposed a feasible binding mode for the first time and provided atomic-level descriptions for the high affinity and specific binding of AS1411. The binding pose predicted by docking was screened using knowledge-based criteria, and a microsecond molecular dynamics (MD) simulation showed the stable existence of the predicted structure in the solution. Structural analysis shows that the unique capping of the 5′ end of AS1411 provides the specific binding with RBD1, and the interactions of hydrogen bond, salt bridge, and water-mediated network between AS1411 and RBD1,2 stabilize the binding. The calculation of per-residue decomposition emphasizes the dominant contribution of van der Waals energy and critical residues are screened. Our study provides the molecular basis of this specific binding and can guide rational AS1411-based aptamers design. Further insights require tight collaborations between the experiments and in silico studies.
Comprehensive landscape of the functions and prognostic value of RNA binding proteins in uterine corpus endometrial carcinoma
Authors: Yao Yong , Liu Kangping , Wu Yuxuan , Zhou Jieyu , Jin Heyue , Zhang Yimin , Zhu Yumin
Published: October 2022

Background: The dysregulation of RNA binding proteins (RBPs) is involved in tumorigenesis and progression. However, information on the overall function of RNA binding proteins in Uterine Corpus Endometrial Carcinoma (UCEC) remains to be studied. This study aimed to explore Uterine Corpus Endometrial Carcinoma-associated molecular mechanisms and develop an RNA-binding protein-associated prognostic model.

Methods: Differently expressed RNA binding proteins were identified between Uterine Corpus Endometrial Carcinoma tumor tissues and normal tissues by R packages (DESeq2, edgeR) from The Cancer Genome Atlas (TCGA) database. Hub RBPs were subsequently identified by univariate and multivariate Cox regression analyses. The cBioPortal platform, R packages (ggplot2), Human Protein Atlas (HPA), and TIMER online database were used to explore the molecular mechanisms of Uterine Corpus Endometrial Carcinoma. Kaplan-Meier (K-M), Area Under Curve (AUC), and the consistency index (c-index) were used to test the performance of our model.

Results: We identified 128 differently expressed RNA binding proteins between Uterine Corpus Endometrial Carcinoma tumor tissues and normal tissues. Seven RNA binding proteins genes (NOP10, RBPMS, ATXN1, SBDS, POP5, CD3EAP, ZC3H12C) were screened as prognostic hub genes and used to construct a prognostic model. Such a model may be able to predict patient prognosis and acquire the best possible treatment. Further analysis indicated that, based on our model, the patients in the high-risk subgroup had poor overall survival (OS) compared to those in the low-risk subgroup. We also established a nomogram based on seven RNA binding proteins. This nomogram could inform individualized diagnostic and therapeutic strategies for Uterine Corpus Endometrial Carcinoma.

Conclusion: Our work focused on systematically analyzing a large cohort of Uterine Corpus Endometrial Carcinoma patients in the The Cancer Genome Atlas database. We subsequently constructed a robust prognostic model based on seven RNA binding proteins that may soon inform individualized diagnosis and treatment.
Regular fecal microbiota transplantation to Senescence Accelerated Mouse-Prone 8 (SAMP8) mice delayed the aging of locomotor and exploration ability by rejuvenating the gut microbiota
Authors: Zhang Nana , Zhang Yan , Wang Zikai , Pan Fei , Ren Rongrong , Li Zhengpeng , Zhao Huijun , Luo Xi , Li Zongwei , Wang Lei , Mo Rui , Sun Gang , Peng Lihua , Ni Ming , Yang Yunsheng
Published: October 2022

Recent evidence points out the role of the gut microbiota in the aging process. However, the specific changes and relevant interventions remain unclear. In this study, Senescence Accelerated Mouse-Prone 8 (SAMP8) mice were divided into four groups; young-FMT-group transplanted fecal microbiota from young donors (2–3°months old) and old-FMT-group transplanted from old donors (10–11°months old); additionally, other two groups either adult mice injected with saline solution or untreated mice served as the saline and blank control groups, respectively. All mice were intervened from their 7-months-old until 13-months-old. The open field test at 9 and 11°months of age showed that the mice transplanted with gut microbiota from young donors had significantly better locomotor and exploration ability than those of transplanted with old-donors gut microbiota and those of saline control while was comparable with the blank control. 16S rRNA gene sequencing showed that the gut microbiome of recipient mice of young donors was altered at 11°months of age, whereas the alternation of the gut microbiome of old-donor recipient mice was at 9°months. For comparison, the recipient mice in the blank and saline control groups exhibited changes in the gut microbiome at 10°months of age. The hallmark of aging-related gut microbiome change was an increase in the relative abundance of Akkermansia, which was significantly higher in the recipients transplanted with feces from older donors than younger donors at 9°months of age. This study shows that fecal microbiota transplantation from younger donors can delay aging-related declines in locomotor and exploration ability in mice by changing the gut microbiome.