bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Translation of Therapies for Spinal Muscular Atrophy
Authors: Shorrock Hannah K. , Gillingwater Thomas H.
Published: February 2023

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterised by widespread loss of lower motor neurons from the spinal cord, leading to progressive weakness and muscle atrophy. SMA is largely caused by homozygous loss of the survival motor neuron (SMN) 1 gene, resulting in reduced levels of full-length SMN protein. Although no approved treatment is currently available for SMA, several clinical trials investigating different approaches to increase SMN levels are showing promising early results. Trials investigating the use of therapies targeting muscle strength and neuroprotective pathways are also in progress, generating the possibility of delivering combination therapies utilising both SMN-dependent and SMN-independent targets. Due to an increased understanding of the cellular and molecular consequences of SMN depletion, a second wave of therapies targeted at pathways downstream of SMN are currently undergoing preclinical development. As these therapies move forward towards the clinic, new treatment options are likely to become available, raising the potential to generate an effective ‘cure’ for SMA.
Reperfusion Strategies for Acute Ischaemic Stroke From Past to Present: An Overview Towards Future Perspectives
Authors: Canavero Isabella , Cavallini Anna , Denaro Federica , Micieli Giuseppe
Published: February 2023

Timely reperfusion of brain ischaemic tissue is the main therapeutic target for acute stroke. In the last few decades many recanalisation strategies have been studied by randomised controlled trials (RCTs), including intravenous (IV), intra-arterial (IA), and combined approaches. Clinical research is addressed to identify the drug associated with the better reperfusion properties and the lower rate of side-effects. To date, according to current evidence-based guidelines, IV tissue plasminogen activator (tPA) is the only approved treatment for acute ischaemic stroke (AIS) within 4.5 hours from onset. Other IV thrombolytics, such as tenecteplase and desmoteplase, have shown promising results in preliminary RCTs and are currently being investigated to produce further evidence. Endovascular catheter-based treatments (including IA administration of thrombolytics or mechanical thrombectomy) have quite inferior feasibility, being performed only by stroke-trained interventional neuroradiologists. Until a few months ago, many trials had investigated the safety and efficacy of endovascular techniques compared with IV tPA without consistent results, limiting their application to patients with contraindications or poor response to IV tPA. More recently, the Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN), Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times (ESCAPE), and Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-arterial (EXTEND-IA) trial results have demonstrated the superiority of endovascular procedures associated with standard care in AIS due to proximal arterial occlusion in the anterior cerebral circulation. These data are going to change the current decision-making process and the care pathway in AIS patients.
Composites With Ceramic Matrix Reinforced With Inorganic and Organic Fillers
Authors: Salieva M. , Tashpolotov Y.
Published: February 2023

The subject of this article is the development of composite materials using ceramic matrices (CM) to increase their strength and reduce the density and brittleness of ceramics. The purpose of this work is to reveal the effect of the content, size, and shape of the introduced fillers on the CM structure, which determines the behavior of CMs. The methods and materials of the study, the analysis of literary sources, as well as the results of the obtained data are considered. For the development of composite materials, we used the loams of the Tyuleikenskoye deposit of the Southern Kyrgyzstan and finely ground basalt powder with organic humate. In addition, we added basalt fibers as an additive. When adding 3-10% of basalt powder to the composition of the clay mass, fire shrinkage decreases slightly. In this limit of additives, the mineralizing effect of the chemical elements of basalt powder and humate on the formation of shards is most effective. With a further increase for additives to 15%, there is an insignificant linear thermal expansion of the samples, which is caused by the phase composition of the shard. At the same time, the optimal firing temperature of raw materials with a content of 3-15% of its additive is 950-1050 °C, within which the main processes of structure formation take place. According to the results of the experiment, the maximum strength of the samples at 1000°C was 15.8-18.8 MPa with the addition of 5% additive, and with an increase in basalt powder and fiber to 15%, the strength was 16.3 MPa. Based on the results obtained, it is possible to use basalt powder and basalt fiber with the addition of humate as the main component in the production of composite ceramic products.
Combined Systems of Photoelectric and Thermal Conversions of Solar Energy
Authors: Ismanov Yu. , Dzhamankyzov N. , Zhumaliev K.
Published: February 2023

The article provides a brief overview of research in the development of combined systems consisting of photovoltaic and thermal solar energy converters. Theoretical, numerical and experimental methods of research in the field of development of combined systems, consisting of photovoltaic and thermal converters of solar energy, have been carried out for almost four decades. Researchers and specialists have repeatedly proposed and evaluated various types of combined systems consisting of photovoltaic and thermal solar energy converters. If you look closely at the history of these developments, you can see that at the beginning of the work, the main efforts were directed to fundamental theories, the consolidation of conceptual ideas and a feasibility study of the main configurations of the design of the collector of combined systems consisting of photovoltaic and thermal solar energy converters. By the early 2000s, research on combined systems consisting of photovoltaic and thermal solar energy converters was more about improving collector design and cost-effectiveness evaluation. More rigorous analyzes of energy and mass transfer phenomena have been carried out on conventional collectors with experimental verification. Ideas for integrated building design began to emerge, and demonstration designs became available for documentation. However, in the last decade, the focus has generally shifted towards the development of complementary products, innovative systems, testing procedures, and design optimization. Numerical analysis becomes more complete with powerful analytical tools. Particular attention was paid to monitoring product reliability, system reliability and environmental impact. It is expected that combined systems consisting of photovoltaic and thermal solar energy converters will be more widely used in the near future, primarily due to environmental necessity.
The Influence of Individual Personality Traits on the Result Creative Work
Authors: Zelenova Yu. , Krasnova M.
Published: February 2023

The article deals with the analysis of the process of students’ creative activity in connection with a set of individual personality traits. The process of teaching students showed that the result of the final product of creative activity is directly affected by the individual characteristics of a person. The stage of inspiration and creative drive alternates with the stage of loss of interest and motivation when creating the author’s concept, which characterizes the main problem of the presented article. The purpose of this work is to find and determine the reasons for the lack of motivation for learning among students of various educational institutions (college, university), courses and areas of study (design, advertising), where creative disciplines are introduced into the curriculum. The classical method of a sociological survey was taken as the main research method, according to the results of which a number of reasons were identified that affect the lack of motivation among students of creative profiles. The decisive issues were the lack of faith in the future, the denial of any teacher on the basis of their own convictions, which automatically creates a reflection on the discipline taught, the desire to replace the learning process with entertainment activities. The factors influencing the formation of a successful personality are identified: self-discipline, motivation, inspiration, an example of a teacher (as an example of an error-free algorithm of actions). As well as the influence of the typology of individuality (based on the theory of C. Jung: introversion and extraversion) on building one’s own image and the result of creative work. Introverts tend to stick to a laconic style and achromatic colors in both clothing and work. Extroverts, on the other hand, prefer bright colors and extravagant style.
Daring to Dare: Edinburgh International Festivals Diary 2022
Authors: Relich Mario
Published: February 2023

Mario Relich provides an annual fixture in Scottish Affairs: a personal review of the Edinburgh International Festivals. Themes for 2022 included freedom of speech and the war on Ukraine.
The Social Power Ideology between Buddhist and Islam Represented in Times Magazine
Authors: Nu’ma Mirfa’un
Published: February 2023

This study aimed to determine the critical discourse analysis of news about Rohingya refugees published by theTimes magazine.The qualitative descriptive method is used as the basis for thinking, and thecritical paradigm is used as the point of view of this analysis. The theoryused is the theory of Power and Domination from Teun Van Dijk. The subject of this research is a discourse leaked by the Times magazine entitled "When Buddhist Go Bad". The results of his research are that the Times Magazine represents the Buddhist doctrine in Myanmar with extreme social power and dominance because it is defended by the Myanmar state to discriminate against Rohingya refugees. Furthermore, as a result of the ideology, socialpower, and domination that the Buddhists own, in the result, the discrimination must be accepted by Rohingya refugees.
Is There a Place for Popular Adult Education in the Managerial University?
Authors: Suoranta Juha
Published: February 2023

This article studies the possibilities of reclaiming and revitalising popular adult education in Finland’s neoliberally driven managerial university and addresses the place for popular adult education in it. In Finland, popular adult education has been taught at a university level since the 1920s. Currently, it has a marginal position in academia. This descriptive case study ponders the role of teaching popular adult education in Finnish universities and describes the pilot program on popular adult education organised at Tampere University in 2020. The study suggests that popular adult education, even in managerial universities, can provide students and practitioners with meaningful knowledge and the means to build global humanity and a sustainable future. In conclusion, the article discusses the future of popular adult education and its role in the university.
The humiliated began to sing
Authors: Kowzan Piotr
Published: February 2023

In this article, the protest songs of teachers on strike were analysed as a traditional pedagogical tool of popular education, social movements, and trade unions. An important context for this was the commodification of the entertainment market, expectations towards the teaching profession, and the state of musical competencies in the population. By identifying what the essence of teaching in the teachers' protest songs was, recommendations for making these activities more educational and politically more effective have been presented. The songs might have played a role in the demise of the strike, in the specific political context, described in the paper. Using the comparisons of teachers to animals by the teachers themselves was a common, but risky tactic.
A novel lipid metabolism gene signature for clear cell renal cell carcinoma using integrated bioinformatics analysis
Authors: Li Ke , Zhu Yan , Cheng Jiawei , Li Anlei , Liu Yuxing , Yang Xinyi , Huang Hao , Peng Zhangzhe , Xu Hui
Published: February 2023

Background: Clear cell renal cell carcinoma (ccRCC), which is the most prevalent type of renal cell carcinoma, has a high mortality rate. Lipid metabolism reprogramming is a hallmark of ccRCC progression, but its specific mechanism remains unclear. Here, the relationship between dysregulated lipid metabolism genes (LMGs) and ccRCC progression was investigated.

Methods: The ccRCC transcriptome data and patients’ clinical traits were obtained from several databases. A list of LMGs was selected, differentially expressed gene screening performed to detect differential LMGs, survival analysis performed, a prognostic model established, and immune landscape evaluated using the CIBERSORT algorithm. Gene Set Variation Analysis and Gene set enrichment analysis were conducted to explore the mechanism by which LMGs affect ccRCC progression. Single-cell RNA-sequencing data were obtained from relevant datasets. Immunohistochemistry and RT-PCR were used to validate the expression of prognostic LMGs.

Results: Seventy-one differential LMGs were identified between ccRCC and control samples, and a novel risk score model established comprising 11 LMGs (ABCB4, DPEP1, IL4I1, ENO2, PLD4, CEL, HSD11B2, ACADSB, ELOVL2, LPA, and PIK3R6); this risk model could predict ccRCC survival. The high-risk group had worse prognoses and higher immune pathway activation and cancer development.

Conclusion: Our results showed that this prognostic model can affect ccRCC progression.
3′-sulfated LewisA/C: An oncofetal epitope associated with metaplastic and oncogenic plasticity of the gastrointestinal foregut
Authors: Das Koushik K. , Brown Jeffrey W.
Published: February 2023

Metaplasia, dysplasia, and cancer arise from normal epithelia via a plastic cellular transformation, typically in the setting of chronic inflammation. Such transformations are the focus of numerous studies that strive to identify the changes in RNA/Protein expression that drive such plasticity along with the contributions from the mesenchyme and immune cells. However, despite being widely utilized clinically as biomarkers for such transitions, the role of glycosylation epitopes is understudied in this context. Here, we explore 3′-Sulfo-Lewis A/C, a clinically validated biomarker for high-risk metaplasia and cancer throughout the gastrointestinal foregut: esophagus, stomach, and pancreas. We discuss the clinical correlation of sulfomucin expression with metaplastic and oncogenic transformation, as well as its synthesis, intracellular and extracellular receptors and suggest potential roles for 3′-Sulfo-Lewis A/C in contributing to and maintaining these malignant cellular transformations.
Assessing the potential of NS2B/NS3 protease inhibitors biomarker in curbing dengue virus infections: In silico vs. In vitro approach
Authors: Norshidah Harun , Leow Chiuan Herng , Ezleen Kamarulzaman Ezatul , Wahab Habibah A. , Vignesh Ramachandran , Rasul Azhar , Lai Ngit Shin
Published: February 2023

An increase in the occurrence of viral infectious diseases is a global concern for human health. According to a WHO report, dengue virus (DENV) is one of the most common viral diseases affecting approximately 400 million people annually, with worsening symptoms in nearly 1% of cases. Both academic and industrial researchers have conducted numerous studies on viral epidemiology, virus structure and function, source and route of infection, treatment targets, vaccines, and drugs. The development of CYD-TDV or Dengvaxia®vaccine has been a major milestone in dengue treatment. However, evidence has shown that vaccines have some drawbacks and limitations. Therefore, researchers are developing dengue antivirals to curb infections. DENV NS2B/NS3 protease is a DENV enzyme essential for replication and virus assembly, making it an interesting antiviral target. For faster hit and lead recognition of DENV targets, methods to screen large number of molecules at lower costs are essential. Similarly, an integrated and multidisciplinary approach involvingin silicoscreening and confirmation of biological activity is required. In this review, we discuss recent strategies for searching for novel DENV NS2B/NS3 protease inhibitors from thein silicoandin vitroperspectives, either by applying one of the approaches or by integrating both. Therefore, we hope that our review will encourage researchers to integrate the best strategies and encourage further developments in this area.
Diagnosis of childhood and adolescent growth hormone deficiency using transcriptomic data
Authors: Garner Terence , Wangsaputra Ivan , Whatmore Andrew , Clayton Peter Ellis , Stevens Adam , Murray Philip George
Published: February 2023

Background

Gene expression (GE) data have shown promise as a novel tool to aid in the diagnosis of childhood growth hormone deficiency (GHD) when comparing GHD children to normal children. The aim of this study was to assess the utility of GE data in the diagnosis of GHD in childhood and adolescence using non-GHD short stature children as a control group.

Methods

GE data was obtained from patients undergoing growth hormone stimulation testing. Data were taken for the 271 genes whose expression was utilized in our previous study. The synthetic minority oversampling technique was used to balance the dataset and a random forest algorithm applied to predict GHD status.

Results

24 patients were recruited to the study and eight subsequently diagnosed with GHD. There were no significant differences in gender, age, auxology (height SDS, weight SDS, BMI SDS) or biochemistry (IGF-I SDS, IGFBP-3 SDS) between the GHD and non-GHD subjects. A random forest algorithm gave an AUC of 0.97 (95% CI 0.93 – 1.0) for the diagnosis of GHD.

Conclusion

This study demonstrates highly accurate diagnosis of childhood GHD using a combination of GE data and random forest analysis.
The association between sex hormones and periodontitis among American adults: A cross-sectional study
Authors: Su Xingyang , Jin Kun , Zhou Xianghong , Zhang Zilong , Zhang Chichen , Li Yifan , Yang Mi , Huang Xinyi , Xu Shishi , Wei Qiang , Cheng Xu , Yang Lu , Qiu Shi
Published: February 2023

Introduction

After adulthood, as a person grows older, the secretion of sex hormones in the body gradually decreases, and the risk of periodontitis increases. But the relationship between sex hormones and periodontitis is still controversial.

Methods

We investigated the association between sex hormones and periodontitis among Americans over 30 years old. 4,877 participants containing 3,222 males and 1,655 postmenopausal females who had had periodontal examination and detailed available sex hormone levels, were included in our analysis from the 2009-2014 National Health and Nutrition Examination Surveys cycles. We applied multivariate linear regression models to estimate the connection between sex hormones and periodontitis after converting sex hormones into categorical variables through tertile. Additionally, to ensure the stability of the analysis results, we carried out a trend test, subgroup analysis, and interaction test.

Results

After fully adjusting the covariates, estradiol levels were not associated with periodontitis in both males and females with a P for trend = 0.064 and 0.064, respectively. For males, we found that sex hormone-binding globulin was positively associated with periodontitis (tertile3 vs tertile1: OR=1.63, 95% CI=1.17-2.28, p = 0.004, P for trend = 0.005). Congruously, free testosterone (tertile3 vs tertile1: OR=0.60, 95% CI=0.43-0.84, p = 0.003), bioavailable testosterone (tertile3 vs tertile1: OR=0.51, 95% CI=0.36-0.71, p < 0.001), and free androgen index (tertile3 vs tertile1: OR=0.53, 95% CI=0.37-0.75, p < 0.001) was found to be negatively associated with periodontitis. Moreover, subgroup analysis of age found a closer relationship between sex hormones and periodontitis in those younger than 50 years.

Conclusion

Our research suggested that males with lower bioavailable testosterone levels affected by sex hormone-binding globulin were at a higher risk of periodontitis. Meanwhile, estradiol levels were not associated with periodontitis in postmenopausal women.
A homozygous KASH5 frameshift mutation causes diminished ovarian reserve, recurrent miscarriage, and non-obstructive azoospermia in humans
Authors: Hou Xiaoning , Zeb Aurang , Dil Sobia , Zhou Jianteng , Zhang Huan , Shi Baolu , Muhammad Zubair , Khan Ihsan , Zaman Qamar , Shah Wasim Akbar , Jiang Xiaohua , Wu Limin , Ma Hui , Shi Qinghua
Published: February 2023

The meiosis-specific LINC complex, composed of the KASH5 and SUN1 proteins, tethers the moving chromosomes to the nuclear envelope to facilitate homolog pairing and is essential for gametogenesis. Here, we applied whole-exome sequencing for a consanguineous family with five siblings suffering from reproductive failure, and identified a homozygous frameshift mutation in KASH5 (c.1270_1273del, p.Arg424Thrfs*20). This mutation leads to the absence of KASH5 protein expression in testes and non-obstructive azoospermia (NOA) due to meiotic arrest before the pachytene stage in the affected brother. The four sisters displayed diminished ovarian reserve (DOR), with one sister never being pregnant but still having dominant follicle at 35 years old and three sisters suffering from at least 3 miscarriages occurring within the third month of gestation. The truncated KASH5 mutant protein, when expressed in cultured cells, displays a similar localization encircling the nucleus and a weakened interaction with SUN1, as compared with the full-length KASH5 proteins, which provides a potential explanation for the phenotypes in the affected females. This study reported sexual dimorphism for influence of the KASH5 mutation on human germ cell development, and extends the clinical manifestations associated with KASH5 mutations, providing genetic basis for the molecular diagnosis of NOA, DOR, and recurrent miscarriage.
Diagnostic performance of artificial intelligence-based computer-aided diagnosis system in longitudinal and transverse ultrasonic views for differentiating thyroid nodules
Authors: Zheng Lin-lin , Ma Su-ya , Zhou Ling , Yu Cong , Xu Hai-shan , Xu Li-long , Li Shi-yan
Published: February 2023

Objective

To evaluate the diagnostic performance of different ultrasound sections of thyroid nodule (TN) using computer-aided diagnosis system based on artificial intelligence (AI-CADS) in predicting thyroid malignancy.

Materials and methods

This is a retrospective study. From January 2019 to July 2019, patients with preoperative thyroid ultrasound data and postoperative pathological results were enrolled, which were divided into two groups: lower risk group (ACR TI-RADS 1, 2 and 3) and higher risk group (ACR TI-RADS 4 and 5). The malignant risk scores (MRS) of TNs were obtained from longitudinal and transverse sections using AI-CADS. The diagnostic performance of AI-CADS and the consistency of each US characteristic were evaluated between these sections. The receiver operating characteristic (ROC) curve and the Cohen κ-statistic were performed.

Results

A total of 203 patients (45.61 ± 11.59 years, 163 female) with 221 TNs were enrolled. The area under the ROC curve (AUC) of criterion 3 [0.86 (95%CI: 0.80~0.91)] was lower than criterion 1 [0.94 (95%CI: 0.90~ 0.99)], 2 [0.93 (95%CI: 0.89~0.97)] and 4 [0.94 (95%CI: 0.90, 0.99)] significantly (P<0.001, P=0.01, P<0.001, respectively). In the higher risk group, the MRS of transverse section was higher than longitudinal section (P<0.001), and the agreement of extrathyroidal extension and shape was moderate and fair (κ =0.48, 0.31 respectively). The diagnostic agreement of other ultrasonic features was substantial or almost perfect (κ >0.60).

Conclusion

The diagnostic performance of computer-aided diagnosis system based on artificial intelligence (AI-CADS) in longitudinal and transverse ultrasonic views for differentiating thyroid nodules (TN) was different, which was higher in the transverse section. It was more dependent on the section for the AI-CADS diagnosis of suspected malignant TNs.
Exposure to environmental air pollutants as a risk factor for primary Sjögren’s syndrome
Authors: Ma Kevin Sheng-Kai , Wang Li-Tzu , Chong Weikun , Lin Cheng-Li , Li Hailang , Chen Aimin , Wei James Cheng-Chung
Published: February 2023

Background

Environmental etiology of primary Sjögren’s syndrome (pSS), an autoimmune disease, has been proposed. This study determined whether the exposure to air pollutants was an independent risk factor for pSS.

Methods

Participants were enrolled from a population-based cohort registry. Daily average concentrations of air pollutants from 2000 to 2011 were divided into 4 quartiles. Adjusted hazard ratios (aHRs) of pSS for exposure to air pollutants were estimated in a Cox proportional regression model adjusting for age, sex, socioeconomic status, and residential areas. A subgroup analysis stratified by sex was conducted to validate the findings. Windows of susceptibility indicated years of exposure which contributed the most to the observed association. Ingenuity Pathway Analysis was used to identify underlying pathways of air pollutant-associated pSS pathogenesis, using Z-score visualization.

Results

Two hundred patients among 177,307 participants developed pSS, with a mean age of 53.1 years at acumulative incidence of 0.11% from 2000 to 2011. Exposure to carbon monoxide (CO), nitric oxide (NO), and methane (CH4) was associated with a higher risk of pSS. Compared to those exposed to the lowest concentration level, the aHRs for pSS were 2.04 (95%CI=1.29-3.25), 1.86 (95%CI=1.22-2.85), and 2.21 (95%CI=1.47-3.31) for those exposed to high levels of CO, NO, and CH4, respectively. The findings persisted in the subgroup analysis, in which females exposed to high levels of CO, NO, and CH4 and males exposed to high levels of CO were associated with significantly great risk of pSS. The cumulative effect of air pollution on pSS was time-dependent. The underlying cellular mechanisms involved chronic inflammatory pathways including the interleukin-6 signaling pathway.

Conclusion

Exposure to CO, NO, and CH4 was associated with a high risk of pSS, which was biologically plausible.
Novel exosome-related risk signature as prognostic biomarkers in glioblastoma
Authors: Ding Mingyan , Xu Qiang , Jin Xiuying , Han Zhezhu , Jiang Hao , Sun Honghua , Jin Yongmin , Piao Zhengri , Zhang Songnan
Published: February 2023

Exosomes are progressively being detected as an indicator for the diagnosis and prognosis of cancer in clinical settings. Many clinical trials have confirmed the impact of exosomes on tumor growth, particularly in anti-tumor immunity and immunosuppression of exosomes. Therefore, we developed a risk score based on genes found in glioblastoma-derived exosomes. In this study, we used the TCGA dataset as the training queue and GSE13041, GSE43378, GSE4412, and CGGA datasets as the external validation queue. Based on machine algorithms and bioinformatics methods, an exosome-generalized risk score was established. We found that the risk score could independently predict the prognosis of patients with glioma, and there were significant differences in the outcomes of patients in the high- and low-risk groups. Univariate and multivariate analyses showed that risk score is a valid predictive biomarker for gliomas. Two immunotherapy datasets, IMvigor210 and GSE78220, were obtained from previous studies. A high-risk score showed a significant association with multiple immunomodulators that could act on cancer immune evasion. The exosome-related risk score could predict the effectiveness of anti-PD-1 immunotherapy. Moreover, we compared the sensitivity of patients with high- and low-risk scores to various anti-cancer drugs and found that patients with high-risk scores had better responses to a variety of anti-cancer drugs. The risk-scoring model established in this study provides a useful tool to predict the total survival time of patients with glioma and guide immunotherapy.
Interactions of pathogenic Escherichia coli with CEACAMs
Authors: Sheikh Alaullah , Fleckenstein James M.
Published: February 2023

The pathogenic Escherichia coli can be parsed into specific variants (pathovars) depending on their phenotypic behavior and/or expression of specific virulence factors. These pathogens are built around chromosomally-encoded core attributes and through acquisition of specific virulence genes that direct their interaction with the host. Engagement of E. coli pathovars with CEACAMs is determined both by core elements common to all E. coli as well as extrachromosomally-encoded pathovar-specific virulence traits, which target amino terminal immunoglobulin variable-like (IgV) regions of CEACAMs. Emerging data suggests that engagement of CEACAMs does not unilaterally benefit the pathogen and that these interactions may also provide an avenue for pathogen elimination.
Peritoneal immune microenvironment of endometriosis: Role and therapeutic perspectives
Authors: Chen Siman , Liu Yukai , Zhong Zhiqi , Wei Chunyan , Liu Yuyin , Zhu Xiaoyong
Published: February 2023

Endometriosis, an estrogen-dependent chronic inflammatory disease characterized by the growth of endometrium-like tissues outside the uterine cavity, affects 10% of reproductive-age women. Although the pathogenesis of endometriosis is uncertain, it is widely accepted that retrograde menstruation results in ectopic endometrial tissue implantation. Given that not all women with retrograde menstruation develop endometriosis, immune factors have been hypothesized to affect the pathogenesis of endometriosis. In this review, we demonstrate that the peritoneal immune microenvironment, including innate immunity and adaptive immunity, plays a central role in the pathogenesis of endometriosis. Current evidence supports the fact that immune cells, such as macrophages, natural killer (NK) cells, dendritic cells (DCs), neutrophils, T cells, and B cells, as well as cytokines and inflammatory mediators, contribute to the vascularization and fibrogenesis of endometriotic lesions, accelerating the implantation and development of ectopic endometrial lesions. Endocrine system dysfunction influences the immune microenvironment through overexpressed estrogen and progesterone resistance. In light of the limitations of hormonal therapy, we describe the prospects for potential diagnostic biomarkers and nonhormonal therapy based on the regulation of the immune microenvironment. Further studies are warranted to explore the available diagnostic biomarkers and immunological therapeutic strategies for endometriosis.
Migratory movements and foraging grounds of endangered green sea turtles in South China Sea based on satellite telemetry during fishing moratorium
Authors: Yu Dongmei , Xia Zhongrong , Yang Xitao , Ng Connie Ka Yan , Yang Kong , Wu Zhenghao , Liu Xiaofeng , Hu Huijian
Published: February 2023

The insights gained from individual tracking can improve the conservation of released young green sea turtles by providing detailed data on migration route, feeding place and habitat distribution. During the fishing moratorium from May 1 to August 16 in 2021, we used satellites to track 6 juvenile green sea turtles released from China’s Huidong Sea Turtle Nature Reserve, and located and reconstructed their migration routes and foraging sea areas. The tracking data shows that the longest tracking time is 91 days, the shortest time is 10 days, and the total tracking time is 213 days, of which three (50%) obtained tracking data for more than one month, and the total movement distances (statistics LC3-LCB) ranges from 124 to 4627 km, while the accurate movement distances (counted by dot pitch above LC0) ranged from 39.5-2331 km. The average daily movement distances ranges from 3.95 to 51.4 km, and the average speed varies between 0.16 to 2.14 km/h. The green turtles released from the China Turtle Bay migrate along the northern coastline of the South China Sea or go straight to the South China Sea. After a month or so, they migrate from Huidong Turtle Bay to Hainan Lingao, Beibu Gulf and Xisha Islands. The northern coast of the South China Sea is one of the migration routes of green sea turtles. Beibu Bay, Zhanjiang Port, Daya Bay, Red Bay, Nan’ao Island, Zhelin Bay and Xisha Islands are important foraging places for green sea turtles. The protection of migration routes and important foraging grounds is one of the key measures to protect sea turtles.
Three-dimensional structure of mesoscale eddies and their interaction with Kuroshio based on observations from a CPIES array
Authors: Ren Qiang , Liu Yansong , Wang Ran , Nan Feng , Wang Jianfeng , Diao Xinyuan , Chen Zifei , Yu Fei , Zhang Chuangzheng , Zhao Ruixiang , Zheng Hua , Zhu Xiao-Hua
Published: February 2023

Mesoscale eddies are widespread in the oceans; however, tracking and observing them remains a challenge. Additionally, there are few studies of eddy–Kuroshio interactions based on large-scale in situ data. Data from a large array of 39 CPIESs deployed around the Luzon Strait in 2018–2019 (12 deployed east of Taiwan within a 3 × grid) were used to reveal the three-dimensional structure of mesoscale eddies and their interaction with Kuroshio. The results show a strengthening (weakening) of the tilt of the pycnocline, which has also caused a deeper (shallower) pycnocline in eastern Taiwan following an anticyclonic (cyclonic) interaction with Kuroshio, which resulted in a strengthening (weakening) of the Kuroshio. During the anticyclonic eddy impinging Kuroshio, the downward (upward) movement at the center of the anticyclonic eddy (Kuroshio) results in a positive (negative) anomaly structure for temperature, with corresponding positive (negative) anomalies for salinity above 600 m in the intermediate layer and negative (positive) anomalies below 600 m. In contrast, when the cyclonic eddies interact with the Kuroshio, the temperature and salinity anomalies change simultaneously, with the temperature showing an overall negative anomaly and the salinity showing a negative and positive anomaly above and below 600 m, respectively. The research in this study provides the basis for further research on energy exchange during eddy–Kuroshio interactions.
Cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in the first-line treatment of non-squamous NSCLC: Evidence from China
Authors: Dai Hongbin , Wang Wenyue , Fan Xin , Chen Yongfa
Published: February 2023

Objective

We aimed to evaluate the cost-effectiveness of camrelizumab plus chemotherapy compared with chemotherapy alone as the first-line treatment for patients with metastatic or advanced non-squamous non-small cell lung cancer (NSCLC) without targetable epidermal growth factor receptor or anaplastic lymphoma kinase genetic aberrations in patients in China.

Methods

A partitioned survival model was constructed to estimate the cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in the first-line treatment of non-squamous NSCLC from a Chinese healthcare perspective. Survival analysis was performed to calculate the proportion of patients in each state using data from trial NCT03134872. The cost of drugs was obtained from Menet, and the cost of disease management was obtained from local hospitals. Health state data were obtained from published literature. Both deterministic sensitivity analyses (DSA) and probabilistic sensitivity analysis (PSA) were adopted to verify the robustness of the results.

Results

Compared with chemotherapy alone, camrelizumab plus chemotherapy provided 0.41 incremental quality-adjusted life years (QALYs) at an incremental cost of $10,482.12. Therefore, the incremental cost-effectiveness ratio of camrelizumab plus chemotherapy was $25,375.96/QALY from the Chinese healthcare perspective, much lower than three times the GDP per capita of China in 2021 ($35,936.09) as the willingness-to-pay threshold. The DSA indicated that the incremental cost-effectiveness ratio was most sensitive to the utility value of progression-free survival, followed by the cost of camrelizumab. The PSA illustrated that camrelizumab had 80% probability of being cost-effective at the threshold of $35,936.09 per QALY gained.

Conclusion

The results suggest that camrelizumab plus chemotherapy is a cost-effective choice in the first-line treatment for patients with non-squamous NSCLC in China. Although this study has limitations such as short time of use of camrelizumab, no adjustment of Kaplan–Meier curves and the median overall survival that has not been reached, the difference in results caused by these factors is relatively small.
D1- and D2-type dopamine receptors are immunolocalized in pial and layer I astrocytes in the rat cerebral cortex
Authors: Oda Satoko , Funato Hiromasa
Published: February 2023

Pial astrocytes, a cellular component of the cerebral cortex surface structure, are observed in a wide range of mammalian species. Despite being recognized as such, the functional potential of pial astrocytes has long been overlooked. Our previous research demonstrated that pial astrocytes exhibit stronger immunoreactivity for muscarinic acetylcholine receptor M1 than protoplasmic astrocytes, indicating sensitivity to neuromodulators. Here, we examined whether pial astrocytes express receptors for dopamine, another crucial neuromodulator of cortical activity. We investigated the immunolocalization of each dopamine receptor subtype (D1R, D2R, D4R, D5R) in the rat cerebral cortex, and compared the intensity of immunoreactivity between pial astrocytes, protoplasmic astrocytes, and pyramidal cells. Our findings revealed that pial astrocytes and layer I astrocytes exhibit stronger D1R- and D4R-immunoreactivity than D2R and D5R. These immunoreactivities were primarily localized in the somata and thick processes of pial and layer I astrocytes. In contrast, protoplasmic astrocytes located in cortical layers II-VI displayed low or negligible immunoreactivities for dopamine receptors. D4R- and D5R-immunopositivity was distributed throughout pyramidal cells including somata and apical dendrites. These findings suggest that the dopaminergic system may regulate the activity of pial and layer I astrocytes via D1R and D4R.
Socioepidemiological macro-determinants associated with the cumulative incidence of bacterial meningitis: A focus on the African Meningitis Belt
Authors: Pinilla-Monsalve Gabriel D. , Llanos-Leyton Natalia , González Maria Camila , Manrique-Hernández Edgar Fabian , Rey-Serrano Juan José , Quiñones-Bautista Jairo Alonso
Published: February 2023

Background

Bacterial meningitis (BM) is a public health challenge as it is associated with high lethality and neurological sequelae. Worldwide, most cases are registered in the African Meningitis Belt (AMB). The role of particular socioepidemiological features is essential for understanding disease dynamics and optimizing policy-making.

Objective

To identify socioepidemiological macro-determinants that contribute to explaining the differences in BM incidence between AMB and the rest of Africa.

Methods

Country-level ecologic study based on the cumulative incidence estimates of the Global Burden of Disease study and reports of the MenAfriNet Consortium. Data about relevant socioepidemiological features were extracted from international sources. Multivariate regression models were implemented to define variables associated with the classification of African countries within the AMB and the incidence of BM worldwide.

Results

Cumulative incidences at the AMB sub-regions were 111.93 (west), 87.23 (central), 65.10 (east), and 42.47 (north) per 100,000 population. A pattern of common origin with continuous exposition and seasonality of cases was observed. Socio-epidemiological determinants contributing to differentiating the AMB from the rest of Africa were household occupancy (OR 3.17 CI 95% 1.09–9.22, p = 0.034) and malaria incidence (OR 1.01 CI 95% 1.00–1.02, p = 0.016). BM cumulative incidence worldwide was additionally associated with temperature and gross national income per capita.

Conclusion

Socioeconomic and climate conditions are macro-determinants associated with BM cumulative incidence. Multilevel designs are required to confirm these findings.
Bacteria commonly associated with central nervous system catheter infections elicit distinct CSF proteome signatures
Authors: Beaver Matthew , Noe Dragana , Thapa Ishwor , Ali Hesham , Snowden Jessica , Kielian Tammy , Skar Gwenn L.
Published: February 2023

Background

Cerebrospinal fluid (CSF) shunt infection is a common and devastating complication of the treatment of hydrocephalus. Timely and accurate diagnosis is essential as these infections can lead to long-term neurologic consequences including seizures, decreased intelligence quotient (IQ) and impaired school performance in children. Currently the diagnosis of shunt infection relies on bacterial culture; however, culture is not always accurate since these infections are frequently caused by bacteria capable of forming biofilms, such as Staphylococcus epidermidis, Cutibacterium acnes, and Pseudomonas aeruginosa resulting in few planktonic bacteria detectable in the CSF. Therefore, there is a critical need to identify a new rapid, and accurate method for diagnosis of CSF shunt infection with broad bacterial species coverage to improve the long-term outcomes of children suffering from these infections.

Methods

To investigate potential biomarkers that would discriminate S. epidermidis, C. acnes and P. aeruginosa central nervous system (CNS) catheter infection we leveraged our previously published rat model of CNS catheter infection to perform serial CSF sampling to characterize the CSF proteome during these infections compared to sterile catheter placement.

Results

P. aeruginosa infection demonstrated a far greater number of differentially expressed proteins when compared to S. epidermidis and C. acnes infection and sterile catheters, and these changes persisted throughout the 56-day time course. S. epidermidis demonstrated an intermediate number of differentially expressed proteins, primarily at early time points that dissipated over the course of infection. C. acnes induced the least amount of change in the CSF proteome when compared to the other pathogens.

Conclusions

Despite the differences in the CSF proteome with each organism compared to sterile injury, several proteins were common across all bacterial species, especially at day 5 post-infection, which are candidate diagnostic biomarkers.
Bacterial meningitis in Africa
Authors: Barichello Tatiana , Rocha Catalão Carlos Henrique , Rohlwink Ursula K. , Kuip Martijn van der , Zaharie Dan , Solomons Regan S. , van Toorn Ronald , Tutu van Furth Marceline , Hasbun Rodrigo , Iovino Federico , Namale Vivian Ssonko
Published: February 2023

Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typically vary with the season and the geographic location, with a high incidence in the meningitis belt of the sub-Saharan area from Senegal to Ethiopia.Streptococcus pneumoniae(pneumococcus) andNeisseria meningitidis(meningococcus) are the main etiological agents of bacterial meningitis in adults and children above the age of one.Streptococcus agalactiae(group B Streptococcus), Escherichia coli, andStaphylococcus aureusare neonatal meningitis's most common causal agents. Despite efforts to vaccinate against the most common causes of bacterial neuro-infections, bacterial meningitis remains a significant cause of mortality and morbidity in Africa, with children below 5 years bearing the heaviest disease burden. The factors attributed to this continued high disease burden include poor infrastructure, continued war, instability, and difficulty in diagnosis of bacterial neuro-infections leading to delay in treatment and hence high morbidity. Despite having the highest disease burden, there is a paucity of African data on bacterial meningitis. In this article, we discuss the common etiologies of bacterial neuroinfectious diseases, diagnosis and the interplay between microorganisms and the immune system, and the value of neuroimmune changes in diagnostics and therapeutics.
Longitudinal analysis of the Non-Motor Symptoms Scale in Parkinson's Disease (NMSS): An exploratory network analysis approach
Authors: Heimrich Konstantin G. , Schönenberg Aline , Mühlhammer Hannah M. , Mendorf Sarah , Santos-García Diego , Prell Tino
Published: February 2023

Introduction

Parkinson's disease (PD) is a multisystem neurodegenerative disorder characterized by motor and non-motor symptoms. In particular, non-motor symptoms have become increasingly relevant to disease progression. This study aimed to reveal which non-motor symptoms have the highest impact on the complex interacting system of various non-motor symptoms and to determine the progression of these interactions over time.

Methods

We performed exploratory network analyses of 499 patients with PD from the Cohort of Patients with Parkinson's Disease in Spain study, who had Non-Motor Symptoms Scale in Parkinson's Disease ratings obtained at baseline and a 2-year follow-up. Patients were aged between 30 and 75 years and had no dementia. The strength centrality measures were determined using the extended Bayesian information criterion and the least absolute shrinkage and selection operator. A network comparison test was conducted for the longitudinal analyses.

Results

Our study revealed that the depressive symptoms anhedonia and feeling sad had the strongest impact on the overall pattern of non-motor symptoms in PD. Although several non-motor symptoms increase in intensity over time, their complex interacting networks remain stable.

Conclusion

Our results suggest that anhedonia and feeling sad are influential non-motor symptoms in the network and, thus, are promising targets for interventions as they are closely linked to other non-motor symptoms.