bluuebunny/crossref_metadata_2025 huggingface dataset:
The idea of a humane civilisation in the works of representatives of the Leningrad philosophical school
Authors: Osipov Igor D. , Rybas Aleksandr E.
Published: October 2022

Considering the fact that at present there is a crisis of modernity, which has not only a political but also a socio-cultural character, the authors of the article try to offer a possible way out of it. Namely, they propose to turn to those socio-philosophical ideas that were developed by representatives of the Leningrad philosophical school in the second half of the 20th century and are almost forgotten at this moment. These ideas, understood through the prism of recent events that have shown the precariousness and insecurity of the unipolar world established after the collapse of the Soviet Union, may well be actualised and used to find the right solutions. The article devotes special attention to the analysis of the socio-philosophical views of V. P. Tugarinov, the dean of the department of philosophy of the Leningrad State University from 1951 to 1960, and V. P. Branskiy, one of the most prominent representatives of the Leningrad philosophical school. It is shown that the idea of humane civilisation, which they conceived as the ideal of social development, meets the theoretical and practical demands of the present. The main characteristics of the humane civilisation are as follows: a pluralistic view of the world, man and society, which, providing freedom of thought and action of people, would not lead to the destruction of society, anarchism in public life or relativism in knowledge; proclamation of freedom the highest value of human life and creation of such social institutions that would be able to guarantee the realisation of freedom in practice; ensuring favourable conditions for the maximum development of personality and moral perfection of man; a critique of bourgeois morality and lifestyle, as well as the pseudo-values of capitalist culture; interpretation of socially significant ideals in the context of the dynamics of social life, as necessary elements of historical development, rather than as eternal truths.
Polarization and Campaign Dynamics in Canada, 1988-2021
Authors: Johnston Richard , Lachance Sarah
Published: October 2022

This paper asks if the increased polarization of sentiment in the Canadian party system has made campaigns less volatile, on the model of the US experience, and if campaigns have also become increasingly important as venues for strategic updating. We unpack the issues in conceptualization and measurement and look at three decades of survey data. But with multiple parties and a single-member plurality electoral system, certain parts of the system may have become more volatile—not less—and may have done so as a consequence of the very polarization that the characterizes the overarching framework. We also conjecture that polarization has increased pressure for within-campaign consolidation of the rival electoral blocks. The conjectures are not borne out. We conclude with speculation on why this is so.
Proposal for a Balanced and Stable International Monetary System
Authors: Rahman Abdurrahman Arum
Published: October 2022

This paper proposes a new model of the international monetary system that could potentially make the system balanced and stable. We call it an “organic system”. We utilize a 3-dimensional simulation of trade and investment involving 5 countries, 20 products, and a 12-month or 5x20x12 model to test the workability of the system. The results show that this model could provide international liquidity to all (member) countries in the world sustainably, eliminate global imbalances to the roots, and make the IMS naturally stable. The simulation also shows that the current accounts, balance sheets, and FX reserves of all member countries tend to be self-sufficient. We implant a digital-and-decentralized system in the very core of the system, which works semi-automatically. This system is flexible; it can start from anywhere in the world and any country may join.
Semaphorin signaling restricts neuronal regeneration in C. elegans
Authors: Harreguy Maria B , Tanvir Zainab , Shah Esha , Simprevil Blandine , Tran Tracy S , Haspel Gal
Published: October 2022

Extracellular signaling proteins serve as neuronal growth cone guidance molecules during development and are well positioned to be involved in neuronal regeneration and recovery from injury. Semaphorins and their receptors, the plexins, are a family of conserved proteins involved in development that, in the nervous system, are axonal guidance cues mediating axon pathfinding and synapse formation. The Caenorhabditis elegans genome encodes for three semaphorins and two plexin receptors: the transmembrane semaphorins, SMP-1 and SMP-2, signal through their receptor, PLX-1, while the secreted semaphorin, MAB-20, signals through PLX-2. Here, we evaluate the locomotion behavior of knockout animals missing each of the semaphorins and plexins and the neuronal morphology of plexin knockout animals; we described the cellular expression pattern of the promoters of all plexins in the nervous system of C. elegans; and we evaluated their effect on the regrowth and reconnection of motoneuron neurites and the recovery of locomotion behavior following precise laser microsurgery. Regrowth and reconnection were more prevalent in the absence of each plexin, while recovery of locomotion surpassed regeneration in all genotypes.
Sex-specific differences in sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary hypertension and chronic thromboembolic pulmonary disease
Authors: Li Hui-Ting , Yuan Ping , Zhao Qin-Hua , Gong Su-Gang , Jiang Rong , Li Jin-Ling , Liu Hong-Ting , Qiu Hong-Ling , Wu Wen-Hui , Luo Ci-Jun , He Jing , Wang Lan , Liu Jin-Ming
Published: October 2022

Objective

Although chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD) are known to be accompanied by symptoms associated with sleep-disordered breathing (SDB) and nocturnal hypoxemia, the sex-specific differences of SDB and nocturnal hypoxemia in patients with CTEPH and CTEPD remain unknown.

Methods

Between July 2020 and August 2022, data were retrieved from 57 males and 63 female patients with CTEPH and CTEPD who underwent sleep study at Shanghai Pulmonary Hospital. Nocturnal mean SpO2 (mean SpO2) < 90% was defined as nocturnal hypoxemia. Logistic and linear regression analysis was performed to assess the predictive value of sleep study indices to hemodynamic parameters. Receiver operating characteristic (ROC) curve was applied to analyze the specific parameters to predict the risk of CTEPH.

Results

SDB was similarly present in males and females, and both sexes predominantly had obstructive sleep apnea (OSA); more women were diagnosed with nocturnal hypoxemia (32 vs. 7%, p = 0.002). SaO2 was negatively associated with mean pulmonary arterial pressure (mPAP) in men (p < 0.001), whereas the ratio of nocturnal SpO2 < 90% of the total monitoring time (T90%) was positively correlated with mPAP. Mean SpO2 was an independent predictor for pulmonary vascular resistance and cardiac output in women (p = 0.001, p < 0.001, p = 0.001, respectively). T90%, SaO2, and minimal SpO2 were combined to develop a new composite parameter: hypoxemia scoring index (HSI). ROC curve analysis indicated that HSI levels of 0.55 could discriminate CTEPH from CTEPD with a sensitivity of 92.3% and specificity of 87.5% in female patients (an area under the curve, 0.937; 95% CI: 0.879–0.995, p < 0.001).

Conclusion

Sex-specific nocturnal hypoxemia was present in patients with CTEPH or CTEPD. In female patients, the HSI showed high capacity for predicting the risk of CTEPH.

Clinical trials registration

Registry: chictr.org.cn; Identifier: ChiCTR-DDD-16009406.
How can blended learning English-as-a-second-language courses incorporate with cultural heritage, building, and sense of sustainable development goals?: A case study
Authors: Kwee Ching Ting Tany , Dos Santos Luis Miguel
Published: October 2022

This study aims to study how the incorporation of digitized heritage buildings into blended English as a second language (ESL) teaching can facilitate Students’ attainment of the Sustainable Development Goals (SDGs) target of quality education, specifically increasing cultural awareness and consciousness of global citizenship. Based on the lens of social cognitive theory and case study approach, the researchers collected qualitative data from 40 participants who enrolled in a blended English-as-a-Second Language course in a community college in the United States. The results indicated that cultural heritage and buildings in the blended language learning curriculum, expanding the knowledge to other subject matter, and beyond the book were the three main themes. Based on the current course and curriculum designs with the elements of cultural heritage, buildings, and senses of SDGs, students expressed positive experiences in the fields of second language acquisition, employments of the computer-aided and technologically assisted tools, and interdisciplinary knowledge. University leaders, department heads, curriculum developers, instructors, and trainers should use this study as the reference to reform and upgrade their current materials with cultural heritage, buildings, and senses of SDGs in order to offer the comprehensive training to college and university students.
Using the changes of several simple anthropometric indices to predict the occurrence of metabolic syndrome: Findings from medically under-resourced communities in rural China
Authors: Li Qiyu , Wang Pengbo , Li Guangxiao , Chang Ye , Guo Xiaofan , Sun Yingxian , Zhang Xingang
Published: October 2022

Background

Various anthropometric indices have been proved to be useful to predict metabolic syndrome(MetS), but the association between changes in anthropometric indices and the onset of MetS is unclear. This study selected six indices that are easy to measure and calculate in daily life and evaluated the relationships.

Methods

We established a prospective cohort in rural China during 2012-2013 and involved 5,221 participants without MetS. The follow-up visit was conducted in 2015 to repeat anthropometric indices measurements and assess MetS onset. Binary logistic regression model was used to calculate the association between changes in anthropometric indices and MetS onset. Receiver operating characteristic (ROC) curve was drawn to compare their abilities in MetS prediction.

Results

Over a median follow-up time of 2.42 years, 1,367 participants (26.2%) developed MetS. The increase in all the six indices is associated with an increased risk of MetS. Changes in WC and WHtR are the strongest predictors, with a 5 cm increase in WC and a 0.025 increase in WHtR giving the best prediction of MetS onset.

Conclusions

People should be aware of changes in these six anthropometric indices in daily life, as their increase is closely related to an increased risk of MetS, especially WC and WHtR. We recommend an increase of 5 cm in WC and 0.025 in WHtR as the optimal cut-off for the MetS prediction.
Effects of microvibration stimulation on developmental potential of discarded germinal vesicle oocytes of human
Authors: Liu Qinli , Zhao Sen , Zhou Jian , Liu Ping , Huo Bo
Published: October 2022

Objective

This research aims to study the effects of continuous microvibration stimulation on the parthenogenetic development of human germinal vesicle oocytes.

Methods

Ninety-five discarded germinal vesicle oocytes from intracytoplasmic sperm injection treatment (ICSI) cycles performed at Amcare Women’s & Children’s Hospital between January and December 2021 were used for conventional static culture as well as 10 Hz microvibration culture. We investigated the differences between the two groups in terms of oocyte maturation rate, parthenogenetic activation rate, and parthenogenetic blastocyst formation rate.

Results

The static culture and 10 Hz microvibration culture of 95 oocytes showed that the parthenogenetic blastocyst formation rate in the microvibration culture group was significantly higher than those in the traditional static culture group.

Conclusion

A continuous microvibration stimulation can significantly improve the parthenogenetic developmental potential of human immature oocytes.
CTGF as a multifunctional molecule for cartilage and a potential drug for osteoarthritis
Authors: Yang Zihuan , Li Weishi , Song Chunli , Leng Huijie
Published: October 2022

CTGF is a multifunctional protein and plays different roles in different cells and under different conditions. Pamrevlumab, a monoclonal antibody against CTGF, is an FDA approved drug for idiopathic pulmonary fibrosis (IPF) and Duchenne muscular dystrophy (DMD). Recent studies have shown that CTGF antibodies may potentially serve as a new drug for osteoarthritis (OA). Expression of CTGF is significantly higher in OA joints than in healthy counterparts. Increasing attention has been attracted due to its interesting roles in joint homeostasis. Joint homeostasis relies on normal cellular functions and cell-cell interactions. CTGF is essential for physiological activities of chondrocytes. Abnormal CTGF expression may cause cartilage degeneration. In this review, the physiological functions of CTGF in chondrocytes and related mechanisms are summarized. Changes in the related signaling pathways due to abnormal CTGF are discussed, which are contributing factors to inflammation, cartilage degeneration and synovial fibrosis in OA. The possibility of CTGF as a potential therapeutic target for OA treatment are reviewed.
Significance of radiofrequency ablation in large solid benign thyroid nodules
Authors: Lin Yan , Shi Yao-ping , Tang Xiao-yin , Ding Min , He Yi , Li Ping , Zhai Bo
Published: October 2022

Objective

The aim of this study is to explore efficacy and safety for radiofrequency ablation (RFA) among cases attacked by large benign solid thyroid nodules, mainly focusing on volume reduction, complication rate, and thyroid function.

Methods and materials

From June 2015 to November 2019, 24 patients with 25 large benign solid thyroid nodules (more than 25 ml) underwent single or sequential RFA in our institution. Eleven nodules achieved complete ablation after single RFA, whereas the other 14 nodules received sequential RFA. Volume reduction in large nodules was evaluated. Following single or sequential RFA, all patients received clinical and ultrasound evaluations, and the median follow-up duration among them was 23.5 months. Technical success, complication rate, and recurrence rate were assessed as well.

Results

In single RFA group, volume reduction ranged from 62.6% to 99.4% (mean ± SD, 93.6 ± 9.9%) 6 months after RFA. In sequential RFA group, volume reduction ranged from 30.6% to 92.9% (mean ± SD, 67.4 ± 17.8%) after the first RFA and was between 83.4% and 98.4% (mean ± SD, 94.8± 3.8%) 6 months after the second RFA. The concentrations of FT3 and FT4 increased slightly 1 day after RFA and returned to normal level 1 month after.

Conclusions

Single or sequential RFA is safe and effective in treating large benign solid thyroid nodules (more than 25 ml) that cause obvious compressive symptoms. Hence, compression symptoms and cosmetic conditions could be effectively improved through single or sequential RFA without marginal recurrence.
Aberrant activation of TGF-β1 induces high bone turnover via Rho GTPases-mediated cytoskeletal remodeling in Camurati-Engelmann disease
Authors: Chen Qi , Yao Yan , Chen Kun , Chen Xihui , Li Bowen , Li Rui , Mo Lidangzhi , Hu Weihong , Zhang Mengjie , Wang Zhen , Wu Yaoping , Wu Yuanming , Liu Fangfang
Published: October 2022

In the adult skeleton, the bone remodeling process involves a dynamic coordination between osteoblasts and osteoclasts, which is disrupted in diseases with high bone turnover rates and dysregulated transforming growth factor beta 1 (TGF-β1). However, little is known about how TGF-β1 signaling mediates bone resorption. Here, we described a pedigree with a heterozygous variant in TGF-β1 (R218C) that resulted in aberrant activation of TGF-β1 through an activating mechanism that caused Camurati-Engelmann disease (CED). We showed that CED patients have high levels of active Rho GTPases and the migration-related proteins Integrin β1 and Integrin β3 in their peripheral blood. HEK293T cells transfected with a plasmid encoding this mutant expressed high levels of TGF-β1 and active Rho GTPases. Furthermore, activation of Rho by TGF-β1 increased osteoclast formation and bone resorption, with increased migration of pre-osteoclasts, as well as cytoskeletal remodeling of pre-osteoclasts and mature osteoclasts. Importantly, pharmacological inhibition of Rho GTPases effectively rescued hyperactive TGF-β1-induced osteoclastogenesis in vitro. Overall, we propose that Rho GTPases mediate TGF-β1-induced osteoclastogenesis and suggest that Rho-TGF-β1 crosstalk is associated with high bone turnover in CED.
Mature and old-growth forests contribute to large-scale conservation targets in the conterminous United States
Authors: DellaSala Dominick A. , Mackey Brendan , Norman Patrick , Campbell Carly , Comer Patrick J. , Kormos Cyril F. , Keith Heather , Rogers Brendan
Published: October 2022

Mature and old-growth forests (MOG) of the conterminous United States collectively support exceptional levels of biodiversity but have declined substantially from logging and development. National-scale proposals to protect 30 and 50% of all lands and waters are useful in assessing MOG conservation targets given the precarious status of these forests. We present the first coast to coast spatially explicit MOG assessment based on three structural development measures—canopy height, canopy cover, and above-ground living biomass to assess relative maturity. MOG were displayed by major forest types (n = 22), landownerships (federal, state, private, and tribal), and Gap Analysis Project (GAP) management status overlaid on the NatureServe’s Red-listed Ecosystems and species, above-ground living biomass, and drinking water source areas. MOG total ∼67.2 M ha (35.9%) of all forest structural classes and were scattered across 8 regions with most in western regions. All federal lands combined represented the greatest (35%) concentrations of MOG, ∼92% of which is on national forest lands with ∼9% on Bureau of Land Management (BLM) and ∼3% on national park lands (totals do not sum to 100% due to minor mapping errors in the datasets). MOG on national forest lands supported the highest concentration of conservation values. However, national forests and BLM lands did not meet lower bound (30%) targets with only ∼24% of MOG in GAP1,2 (5.9 M ha) protection status. The vast majority (76%, 20.8 M ha) of MOG on federal lands that store 10.64 Gt CO2 (e) are vulnerable to logging (GAP3). If federal MOG are logged over a decade, and half their carbon stock emitted, there would be an estimated 0.5 ppm increase in atmospheric CO2 by 2030, which is equivalent to ∼9% of United States total annual emissions. We recommend upper bound (100%) protection of federal MOG, including elevating the conservation status of Inventoried Roadless Areas. This would avoid substantial CO2 emissions while allowing ongoing carbon sequestration to act as natural climate solutions to aid compliance with the Paris Climate Agreement and presidential executive orders on MOG and 30% of all lands and waters in protection by 2030. On non-federal lands, which have fewer MOG, regulatory improvements and conservation incentives are needed.
Genome-wide association study for systemic lupus erythematosus in an egyptian population
Authors: Elghzaly Ashraf A. , Sun Celi , Looger Loren L. , Hirose Misa , Salama Mohamed , Khalil Noha M. , Behiry Mervat Essam , Hegazy Mohamed Tharwat , Hussein Mohamed Ahmed , Salem Mohamad Nabil , Eltoraby Ehab , Tawhid Ziyad , Alwasefy Mona , Allam Walaa , El-Shiekh Iman , Elserafy Menattallah , Abdelnaser Anwar , Hashish Sara , Shebl Nourhan , Shahba Abeer Abdelmonem , Elgirby Amira , Hassab Amina , Refay Khalida , El-Touchy Hanan Mohamed , Youssef Ali , Shabacy Fatma , Hashim Abdelkader Ahmed , Abdelzaher Asmaa , Alshebini Emad , Fayez Dalia , El-Bakry Samah A. , Elzohri Mona H. , Abdelsalam Eman Nagiub , El-Khamisy Sherif F. , Ibrahim Saleh , Ragab Gaafar , Nath Swapan K.
Published: October 2022

Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians–an admixed North African/Middle Eastern population–using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10−8) and eight novel suggestive loci (Pcorrected < 1.0 × 10−5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10−95 < p < 1.0 × 10−2) across diverse tissues. These loci are involved in cellular proliferation and invasion—pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.
Case report: Functional characterization of a de novo c.145G>A p.Val49Met pathogenic variant in a case of PIGA-CDG with megacolon
Authors: Salinas-Marín Roberta , Murakami Yoshiko , González-Domínguez Carlos Alberto , Cruz-Muñoz Mario Ernesto , Mora-Montes Héctor Manuel , Morava Eva , Kinoshita Taroh , Monroy-Santoyo Susana , Martínez-Duncker Iván
Published: October 2022

A subgroup of congenital disorders of glycosylation (CDGs) includes inherited GPI-anchor deficiencies (IGDs) that affect the biosynthesis of glycosylphosphatidylinositol (GPI) anchors, including the first reaction catalyzed by the X-linkedPIGA. Here, we show the first PIGA-CDG case reported in Mexico in a male child with a moderate-to-severe phenotype characterized by neurological and gastrointestinal symptoms, including megacolon. Exome sequencing identified the hemizygous variantPIGAc.145G>A (p.Val49Met), confirmed by Sanger sequencing and characterized asde novo. The pathogenicity of this variant was characterized by flow cytometry and complementation assays in PIGA knockout (KO) cells.
Case report: A rare case of coexisting Waldenstrom Macroglobulinemia and B-cell acute lymphoblastic leukemia with KMT2D and MECOM mutations
Authors: Wang Lingling , Tang Jiao , Feng Jun , Huang Yongfen , Cheng Yuexin , Xu Hao , Miao Yuqing
Published: October 2022

Background

Waldenstrom Macroglobulinemia (WM) is a rare and indolent lymphoma of B-cell origin characterized by elevated monoclonal IgM, with MYD88L265P mutation and CXCR4 mutation as common molecular alterations. B-cell Acute Lymphoblastic Leukemia (B-ALL) is clinically heterogeneous, characterized by abnormal proliferation and aggregation of immature lymphocytes in the bone marrow and lymphoid tissue. WM and ALL are hematologic malignancies of B-cell origin with completely different clinical manifestations and biological features. KMT2D and MECOM mutations are very rare in ALL and usually indicate poor disease prognosis. The coexistence of WM and ALL with KMT2D and MECOM mutations have not been reported.

Case presentation

A 74-year-old female patient was diagnosed with WM in July 2018 and received four cycles of chemotherapy of bortezomib and dexamethasone. In November 2018, she received immunomodulator thalidomide as maintenance therapy. In November 2020, Bruton’s Tyrosine Kinase inhibitors (BTKi) has been introduced into the Chinese market and she took zanubrutinib orally at a dose of 80 mg per day. The disease remained in remission. In December 2021, she presented with multiple enlarged lymph nodes throughout the body. Bone marrow and next-generation sequencing (NGS) suggested the coexistence of WM and B-ALL with KMT2D and MECOM mutations. The patient was treated with zanubrutinib in combination with vincristine and dexamethasone, after which she developed severe myelosuppression and septicemia. The patient finally got remission. Due to the patient’s age and poor status, she refused intravenous chemotherapy and is currently treated with zanubrutinib.

Conclusions

The coexistence of WM and B-ALL is very rare and has not been reported. The presence of both KMT2D and MECOM mutations predicts a poor prognosis and the possibility of insensitivity to conventional treatment options. BTKi achieves its anti-tumor effects by inhibiting BTK activation and blocking a series of malignant transformations in B-cell tumors. In addition, it also acts on T-cell immunity and tumor microenvironment. Combination therapy based on BTKi may improve the prognosis of this patient.
Not all autoantibodies are clinically relevant. Classic and novel autoantibodies in Sjögren’s syndrome: A critical review
Authors: Vílchez-Oya Francisco , Balastegui Martin Hector , García-Martínez E. , Corominas Hèctor
Published: October 2022

Sjögren’s syndrome (SjS) is a heterogeneous systemic disease. The abnormal responses to La/SSB and Ro/SSA of both B-cells and T-cells are implicated as well as others, in the destruction of the epithelium of the exocrine glands, whose tissue characteristically shows a peri-epithelial lymphocytic infiltration that can vary from sicca syndrome to systemic disease and lymphoma. Despite the appearance of new autoantibodies, anti-Ro/SSA is still the only autoantibody included in the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria and is used extensively as a traditional biomarker in clinical practice. The study and findings of new autoantibodies in SjS has risen in the previous decade, with a central role given to diagnosis and elucidating new aspects of SjS physiopathology, while raising the opportunity to establish clinical phenotypes with the goal of predicting long-term complications. In this paper, we critically review the classic and the novel autoantibodies in SjS, analyzing the methods employed for detection, the pathogenic role and the wide spectrum of clinical phenotypes.
Glial receptor PLXNB2 regulates schizophrenia-related stress perception via the amygdala
Authors: Xuan Fang-Ling , Yan Ling , Li Yanli , Fan Fengmei , Deng Hu , Gou Mengzhuang , Chithanathan Keerthana , Heinla Indrek , Yuan Liang , Seppa Kadri , Zharkovsky Alexander , Kalda Anti , Hong L. Elliot , Hu Guo-Fu , Tan Yunlong , Tian Li
Published: October 2022

Stress is a trigger for the development of psychiatric disorders. However, how stress trait differs in schizophrenia patients is still unclear. Stress also induces and exacerbates immune activation in psychiatric disorders. Plexins (Plxn) and its ligands semaphorins (Sema) are important cellular receptors with plural functions in both the brain and the immune system. Recently, the role of Plxn/Sema in regulation of neuroinflammation was also noticed. Here, when investigating immune mechanisms underlying stress susceptibility in schizophrenia, we discovered the role of Plxnb2 in stress response. Patients of first-episode schizophrenia (FES) with high stress (FES-hs, n=51) and low stress (FES-ls, n=50) perception and healthy controls (HCs) (n=49) were first recruited for neuroimaging and blood bulk RNA sequencing (RNA-seq). A mouse model of chronic unpredictable stress (CUS) and intra-amygdaloid functional blocking of Plxnb2 were further explored to depict target gene functions. Compared to HCs, FES-hs patients had bigger caudate and thalamus (FDR=0.02&0.001, respectively) whereas FES-ls patients had smaller amygdala (FDR=0.002). Blood RNA-seq showed differentially expressed PLXNB2 and its ligands among patient groups and HCs (FDR<0.05~0.01). Amygdaloid size and PLXNB2 level were both negatively correlated with stress perception (p<0.01&0.05, respectively), which fully mediated the amygdaloid positive association with PLXNB2 expression (β=0.9318, 95% CI: 0.058~1.886) in FES-hs patients. In mice, Plxnb2 was enriched in astrocytes and microglia and CUS reduced its expression in astrocytes (p<0.05). Inhibition of amygdaloid Plxnb2 by its functional blocking monoclonal antibody (mAb)-102 induced mice anxiety (p<0.05), amygdaloid enlargement (p<0.05), and microglial ramification (p<0.001) compared to saline. These data suggest that PLXNB2 regulates amygdala-dependent stress responses.
High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1
Authors: Cai Tiantian , Du Peng , Suo Lixia , Jiang Xiaozhen , Qin Qiu , Song Ronghua , Yang Xiaorong , Jiang Yanfei , Zhang Jin-an
Published: October 2022

Autoimmune thyroid disease (AITD), the most common autoimmune disease, includes Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Currently, the pathogenesis of AITD is not fully understood. Our study aimed to examine the presence of macrophage polarization imbalance in AITD patients, to investigate whether high iodine can cause macrophage polarization imbalance, and to investigate the role of key genes of metabolic reprogramming in macrophage polarization imbalance caused by high iodine. We synergistically used various research strategies such as systems biology, clinical studies, cell culture and mouse disease models. Gene set enrichment analysis (GSEA) revealed that M1 macrophage hyperpolarization was involved in the pathogenesis of AITD. In vitro and in vivo experiments showed that high iodine can affect the polarization of M1 or M2 macrophages and their related cytokines. Robust rank aggregation (RRA) method revealed that hexokinase 3 (HK3) was the most aberrantly expressed metabolic gene in autoimmune diseases. In vitro and in vivo studies revealed HK3 could mediate macrophage polarization induced by high iodine. In summary, hyperpolarization of M1-type macrophages is closely related to the pathogenesis of AITD. High iodine can increase HK3 expression in macrophages and promote macrophage polarization towards M1. Targeting HK3 can inhibit M1 polarization induced by high iodine.
Immunogenic cell death-related risk signature predicts prognosis and characterizes the tumour microenvironment in lower-grade glioma
Authors: Cai Jiayang , Hu Yuanyuan , Ye Zhang , Ye Liguo , Gao Lun , Wang Yixuan , sun Qian , Tong Shiao , Yang Ji’an , Chen Qianxue
Published: October 2022

Lower-grade glioma (LGG) is a common malignant primary tumour in the central nervous system, and most patients eventually develop highly aggressive gliomas despite comprehensive traditional treatment. Tumour molecular subtypes and prognostic biomarkers play a crucial role in LGG diagnosis and treatment. Therefore, the identification of novel biomarkers in LGG patients is crucial for predicting the prognosis of glioma. Immunogenic cell death (ICD) is defined as regulated cell death that is sufficient to activate the adaptive immune response of immunocompetent hosts. The combination of ICD and immunotherapy might exert a greater and more persistent antitumour effect in gliomas. In our study, we explored the expression, function, and genetic alterations of 34 ICD-related genes. Using 12 ICD-related genes, including IL17RA, IL1R1, EIF2AK3, CD4, PRF1, CXCR3, CD8A, BAX, PDIA3, CASP8, MYD88, and CASP1, we constructed and validated an ICD-related risk signature via least absolute shrinkage and selection operator (LASSO) Cox regression analysis. All the information was obtained from public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and the Chinese Glioma Genome Atlas (CGGA) databases. Our results revealed that ICD-high risk groups have a poor prognosis and might be more sensitive to immune checkpoint blockade (ICB) immunotherapy. In addition, ICD-high risk groups were associated with 1p19q noncodeletion, higher WHO grade, wild type IDH, and an immunosuppressive tumour microenvironment. We verified the prognostic value of 12 ICD-related genes in TCGA and CGGA databases. Immunohistochemistry was performed to verify the expression of several ICD-related genes at the protein level. Our study provides a novel and comprehensive perspective to elucidate the underlying mechanisms of LGG prognosis and direction for future individualized cancer immunotherapy.
Promising strategy for developing mRNA-based universal influenza virus vaccine for human population, poultry, and pigs– focus on the bigger picture
Authors: Rcheulishvili Nino , Papukashvili Dimitri , Liu Cong , Ji Yang , He Yunjiao , Wang Peng George
Published: October 2022

Since the first outbreak in the 19th century influenza virus has remained emergent owing to the huge pandemic potential. Only the pandemic of 1918 caused more deaths than any war in world history. Although two types of influenza– A (IAV) and B (IBV) cause epidemics annually, influenza A deserves more attention as its nature is much wilier. IAVs have a large animal reservoir and cause the infection manifestation not only in the human population but in poultry and domestic pigs as well. This many-sided characteristic of IAV along with the segmented genome gives rise to the antigenic drift and shift that allows evolving the new strains and new subtypes, respectively. As a result, the immune system of the body is unable to recognize them. Importantly, several highly pathogenic avian IAVs have already caused sporadic human infections with a high fatality rate (~60%). The current review discusses the promising strategy of using a potentially universal IAV mRNA vaccine based on conserved elements for humans, poultry, and pigs. This will better aid in averting the outbreaks in different susceptible species, thus, reduce the adverse impact on agriculture, and economics, and ultimately, prevent deadly pandemics in the human population.
Alterations in circulating markers in HIV/AIDS patients with poor immune reconstitution: Novel insights from microbial translocation and innate immunity
Authors: Xiao Qing , Yu Fengting , Yan Liting , Zhao Hongxin , Zhang Fujie
Published: October 2022

After long-term anti-retroviral therapy (ART) treatment, most human immunodeficiency virus (HIV)/Acquired Immure Deficiency Syndrome (AIDS) patients can achieve virological suppression and gradual recovery of CD4+ T-lymphocyte (CD4+ T cell) counts. However, some patients still fail to attain normal CD4+ T cell counts; this group of patients are called immune non-responders (INRs), and these patients show severe immune dysfunction. The potential mechanism of poor immune reconstitution (PIR) remains unclear and the identification of uniform biomarkers to predict the occurrence of PIR is particularly vital. But limited information is available on the relationship between circulating markers of INRs and immune recovery. Hence, this review summarises alterations in the intestine microbiota and associated markers in the setting of PIR to better understand host-microbiota-metabolite interactions in HIV immune reconstitution and to identify biomarkers that can predict recovery of CD4+ T cell counts in INRs.
Autofluorescence identifies highly phagocytic tissue-resident macrophages in mouse and human skin and cutaneous squamous cell carcinoma
Authors: Bourdely Pierre , Petti Luciana , Khou Sokchea , Meghraoui-Kheddar Aida , Elaldi Roxane , Cazareth Julie , Mossadegh-Keller Noushine , Boyer Julien , Sieweke Michael H. , Poissonnet Gilles , Sudaka Anne , Braud Veronique M. , Anjuère Fabienne
Published: October 2022

Macrophages from human and mouse skin share phenotypic and functional features, but remain to be characterized in pathological skin conditions. Skin-resident macrophages are known to derive from embryonic precursors or from adult hematopoiesis. In this report, we investigated the origins, phenotypes and functions of macrophage subsets in mouse and human skin and in cutaneous squamous cell carcinoma (cSCC) using the spectral flow cytometry technology that enables cell autofluorescence to be considered as a full-fledged parameter. Autofluorescence identifies macrophage subsets expressing the CD206 mannose receptor in human peri-tumoral skin and cSCC. In mouse, all AF+ macrophages express the CD206 marker, a subset of which also displaying the TIM-4 marker. While TIM-4-CD206+ AF+ macrophages can differentiate from bone-marrow monocytes and infiltrate skin and tumor, TIM-4 identifies exclusively a skin-resident AF+ macrophage subset that can derive from prenatal hematopoiesis which is absent in tumor core. In mouse and human, AF+ macrophages from perilesional skin and cSCC are highly phagocytic cells contrary to their AF- counterpart, thus identifying autofluorescence as a bona fide marker for phagocytosis. Our data bring to light autofluorescence as a functional marker characterizing subsets of phagocytic macrophages in skin and cSCC. Autofluorescence can thus be considered as an attractive marker of function of macrophage subsets in pathological context.
Lactobacillus (LA-1) and butyrate inhibit osteoarthritis by controlling autophagy and inflammatory cell death of chondrocytes
Authors: Cho Keun-Hyung , Na Hyun Sik , Jhun JooYeon , Woo Jin Seok , Lee A Ram , Lee Seung Yoon , Lee Jeong Su , Um In Gyu , Kim Seok Jung , Park Sung-Hwan , Cho Mi-La
Published: October 2022

Osteoarthritis (OA) reduces the quality of life as a result of the pain caused by continuous joint destruction. Inactivated Lactobacillus (LA-1) ameliorated osteoarthritis and protected cartilage by modulating inflammation. In this study, we evaluated the mechanism by which live LA-1 ameliorated OA. To investigate the effect of live LA-1 on OA progression, we administered LA-1 into monosodium iodoacetate (MIA)-induced OA animals. The pain threshold, cartilage damage, and inflammation of the joint synovial membrane were improved by live LA-1. Furthermore, the analysis of intestinal tissues and feces in the disease model has been shown to affect the systems of the intestinal system and improve the microbiome environment. Interestingly, inflammation of the intestinal tissue was reduced, and the intestinal microbiome was altered by live LA-1. Live LA-1 administration led to an increase in the level of Faecalibacterium which is a short-chain fatty acid (SCFA) butyrate-producing bacteria. The daily supply of butyrate, a bacterial SCFA, showed a tendency to decrease necroptosis, a type of abnormal cell death, by inducing autophagy and reversing impaired autophagy by the inflammatory environment. These results suggest that OA is modulated by changes in the gut microbiome, suggesting that activation of autophagy can reduce aberrant cell death. In summary, live LA-1 or butyrate ameliorates OA progression by modulating the gut environment and autophagic flux. Our findings suggest the regulation of the gut microenvironment as a therapeutic target for OA.
Microbial dysbiosis and lack of SCFA production in a Spanish cohort of patients with multiple sclerosis
Authors: Moles Laura , Delgado Susana , Gorostidi-Aicua Miriam , Sepúlveda Lucía , Alberro Ainhoa , Iparraguirre Leire , Suárez Jose Alberto , Romarate Leire , Arruti Maialen , Muñoz-Culla Maider , Castillo-Triviño Tamara , Otaegui David ,   The international Multiple Sclerosis Microbiome Study Consortium
Published: October 2022

Background

Multiple sclerosis (MS) is a chronic, demyelinating, and immune-mediated disease of the central nervous system caused by a combination of genetic, epigenetic, and environmental factors. The incidence of MS has increased in the past several decades, suggesting changes in the environmental risk factors. Much effort has been made in the description of the gut microbiota in MS; however, little is known about the dysbiosis on its function. The microbiota produces thousands of biologically active substances among which are notable the short-chain fatty acid (SCFA) excretion.

Objectives

Analyze the interaction between microbiota, SCFAs, diet, and MS.

Methods

16S, nutritional questionnaires, and SCFAS quantification have been recovered from MS patients and controls.

Results

Our results revealed an increment in the phylum Proteobacteria, especially the family Enterobacteriaceae, a lack in total SCFA excretion, and an altered profile of SCFAs in a Spanish cohort of MS patients. These alterations are more evident in patients with higher disability.

Conclusions

The abundance of Proteobacteria and acetate and the low excretion of total SCFAs, especially butyrate, are common characteristics of MS patients, and besides, both are associated with a worse prognosis of the disease.
miRNA profile at diagnosis predicts treatment outcome in patients with B-chronic lymphocytic leukemia: A FILO study
Authors: Duroux-Richard Isabelle , Gagez Anne-Laure , Alaterre Elina , Letestu Rémi , Khalifa Olfa , Jorgensen Christian , Leprêtre Stéphane , Tchernonog Emmanuelle , Moreaux Jérôme , Cartron Guillaume , Apparailly Florence
Published: October 2022

During many years, chemo-immunotherapy fludarabine-cyclophosphamide-rituximab (FCR) was the gold standard for first line treatment of medically fit patients with symptomatic B-chronic lymphocytic leukemia (CLL). Over the last decade, targeted biotherapies have revolutionized the treatment of B-CLL patients and almost entirely supplanted FCR. However, no biomarker still exists to predict the complete remission (CR) with undetectable minimal residual disease (uMRD) in bone marrow (BM), which remains the best predictive factor for survival. MicroRNAs represent a class of molecular biomarkers which expression is altered in B-CLL. Our study aimed at identifying before treatment blood miRNAs that predict treatment outcome in previously untreated B-CLL patients (NCT 01370772, https://clinicaltrials.gov/ct2/show/NCT01370772). Using hierarchical clustering of miRNA expression profiles discriminating 8 patients who achieved CR with BM uMRD from 8 patients who did not achieve CR and displayed detectable BM MRD, we identified 25 miRNAs differentially expressed before treatment. The expression of 11 miRNAs was further validated on a larger cohort (n=123). Based on the dosage of 5 miRNAs at diagnosis, a decision tree was constructed to predict treatment outcome. We identified 6 groups of patients with a distinct probability of being CR with BM uMRD to FCR treatment, ranging from 72% (miR-125b, miR-15b and miR-181c high) to 4% (miR-125b and miR-193b low). None of the patients displaying high expression levels of miR-125b, miR-15b and miR-181c relapsed during study follow-up. In contrast, patients with low miR-15b and high miR-412, or with low miR-125b and miR-193b, demonstrated significant low PFS. RNA sequencing of blood at diagnosis identified that patients relapsing after treatment are characterized by significant enrichment of gene signatures related to cell cycle, MYC target genes, metabolism and translation regulation. Conversely, patients achieving CR with BM uMRD displayed significant enrichment in genes related to communication between CLL cells and the microenvironment, immune system activation and upregulation of polycomb PRC2 complex target genes. Our results suggest that blood miRNAs are potent predictive biomarkers for FCR treatment efficacy and might be implicated in the FCR efficacy in B-CLL patients, providing new insight into unmet need for the treatment of B-CLL patients and identifying pathways predictive of patients’ remission.

Clinical trial registration

ClinicalTrials.gov, identifier NCT 01370772.
Salvage high intensity focused ultrasound for residual or recurrent cervical cancer after definitive chemoradiotherapy
Authors: Zhong Qin , Tang Fei , Ni Tingting , Chen Yanping , Liu Yuncong , Wu Jing , Zhou Wen , Feng Zhiyu , Lu Xiaokai , Tan Shisheng , Zhang Yu
Published: October 2022

Objective

The treatment of residual/recurrent cervical cancer within a previously irradiated area is challenging and generally associated with a poor outcome. Local treatments such as salvage surgery and re-irradiation are usually traumatic and have limited efficacy. High intensity focused ultrasound (HIFU) treatment can directly ablate solid tumors without damaging neighboring healthy tissue. However, the HIFU studies for these patients are limited. Experience gained over the course of 10 years with the use of HIFU for the management of residual/recurrent cervical cancer after chemoradiotherapy is reported herein.

Methods

153 patients with residual/recurrent cervical cancer in a previously irradiated field who received HIFU treatment between 2010 and 2021 were retrospectively analyzed. Adverse effects, survival benefit and factors affecting prognosis were given particular attention.

Results

A total of 36 patients (23.5%) achieved a partial response following HIFU treatment and 107 patients (69.9%) had stable disease. The objective response and disease control rates were 23.5% and 93.5%, respectively. The median progression-free survival (mPFS) and median overall survival (mOS) were 17.0 months and 24.5 months, respectively. Moreover, patients with lesions ≥1.40 cm before HIFU treatment and a shrinkage rate ≥ 30% after treatment had a higher mPFS and mOS, and patients with lesions ≤1.00 cm after HIFU treatment had a higher mPFS (P=<0.05). All the treatment-related adverse events were limited to minor complications, which included skin burns, abdominal pain and vaginal discharge.

Conclusions

HIFU treatment is likely a preferred option for cervical cancer patients with residual disease or recurrence following CRT that can safely improve the local control rate and extend survival.
Genomic consequences and selection efficacy in sympatric sexual versus asexual kelps
Authors: Vranken Sofie , Scheben Armin , Batley Jacqueline , Wernberg Thomas , Coleman Melinda Ann
Published: October 2022

Genetic diversity can influence resilience and adaptative capacity of organisms to environmental change. Genetic diversity within populations is largely structured by reproduction, with the prevalence of asexual versus sexual reproduction often underpinning important diversity metrics that determine selection efficacy. Asexual or clonal reproduction is expected to reduce genotypic diversity and slow down adaptation through reduced selection efficacy, yet the evolutionary consequences of clonal reproduction remain unclear for many natural populations. Here, we examine the genomic consequences of sympatric sexual (haplodiplontic) and clonal morphs of the kelp Ecklonia radiata that occur interspersed on reefs in Hamelin Bay, Western Australia. Using genome-wide single nucleotide polymorphisms, we confirm significant asexual reproduction for the clonal populations, indicated by a significantly lower number of multi-locus lineages and higher intra-individual diversity patterns (individual multi-locus heterozygosity, MLH). Nevertheless, co-ancestry analysis and breeding experiments confirmed that sexual reproduction by the clonal morph and interbreeding between the two morphs is still possible, but varies among populations. One clonal population with long-term asexuality showed trends of decreased selection efficacy (increased ratio non- vs. synonymous gene diversities). Yet, all clonal populations showed distinct patterns of putative local adaptation relative to the sexual morph, possibly indicating maladaptation to local environmental conditions and high vulnerability of this unique clonal morph to environmental stress.