bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing Village-Level Targeting of Active Case Detection to Support Visceral Leishmaniasis Elimination in India
Authors: Bindroo Joy , Priyamvada Khushbu , Chapman Lloyd A. C. , Mahapatra Tanmay , Sinha Bikas , Banerjee Indranath , Mishra Prabhas Kumar , Rooj Basab , Kundan Kumar , Roy Nupur , Gill Naresh Kumar , Hightower Allen , Sharma Madan Prasad , Dhingra Neeraj , Bern Caryn , Srikantiah Sridhar
Published: March 2021

Background

India has made major progress in improving control of visceral leishmaniasis (VL) in recent years, in part through shortening the time infectious patients remain untreated. Active case detection decreases the time from VL onset to diagnosis and treatment, but requires substantial human resources. Targeting approaches are therefore essential to feasibility.

Methods

We analyzed data from the Kala-azar Management Information System (KAMIS), using village-level VL cases over specific time intervals to predict risk in subsequent years. We also graphed the time between cases in villages and examined how these patterns track with village-level risk of additional cases across the range of cumulative village case-loads. Finally, we assessed the trade-off between ACD effort and yield.

Results

In 2013, only 9.3% of all villages reported VL cases; this proportion shrank to 3.9% in 2019. Newly affected villages as a percentage of all affected villages decreased from 54.3% in 2014 to 23.5% in 2019, as more surveillance data accumulated and overall VL incidence declined. The risk of additional cases in a village increased with increasing cumulative incidence, reaching approximately 90% in villages with 12 cases and 100% in villages with 45 cases, but the vast majority of villages had small cumulative case numbers. The time-to-next-case decreased with increasing case-load. Using a 3-year window (2016–2018), a threshold of seven VL cases at the village level selects 329 villages and yields 23% of cases reported in 2019, while a threshold of three cases selects 1,241 villages and yields 46% of cases reported in 2019. Using a 6-year window increases both effort and yield.

Conclusion

Decisions on targeting must consider the trade-off between number of villages targeted and yield and will depend upon the operational efficiencies of existing programs and the feasibility of specific ACD approaches. The maintenance of a sensitive, comprehensive VL surveillance system will be crucial to preventing future VL resurgence.
Profiles of 5α-Reduced Androgens in Humans and Eels: 5α-Dihydrotestosterone and 11-Ketodihydrotestosterone Are Active Androgens Produced in Eel Gonads
Authors: Yazawa Takashi , Inaba Hiroyuki , Imamichi Yoshitaka , Sekiguchi Toshio , Uwada Junsuke , Islam Mohammad Sayful , Orisaka Makoto , Mikami Daisuke , Ida Takanori , Sato Takahiro , Miyashiro Yoshimichi , Takahashi Satoru , Khan Md. Rafiqul Islam , Suzuki Nobuo , Umezawa Akihiro , Kitano Takeshi
Published: March 2021

Although 11-ketotestosterone (11KT) and testosterone (T) are major androgens in both teleosts and humans, their 5α-reduced derivatives produced by steroid 5α-reductase (SRD5A/srd5a), i.e., 11-ketodihydrotestosterone (11KDHT) and 5α-dihydrotestosterone (DHT), remains poorly characterized, especially in teleosts. In this study, we compared the presence and production of DHT and 11KDHT in Japanese eels and humans. Plasma 11KT concentrations were similar in both male and female eels, whereas T levels were much higher in females. In accordance with the levels of their precursors, 11KDHT levels did not show sexual dimorphism, whereas DHT levels were much higher in females. It is noteworthy that plasma DHT levels in female eels were higher than those in men. In addition, plasma 11KDHT was undetectable in both sexes in humans, despite the presence of 11KT. Three srd5a genes (srd5a1, srd5a2a and srd5a2b) were cloned from eel gonads. All three srd5a genes were expressed in the ovary, whereas only both srd5a2 genes were expressed in the testis. Human SRD5A1 was expressed in testis, ovary and adrenal, whereas SRD5A2 was expressed only in testis. Human SRD5A1, SRD5A2 and both eel srd5a2 isoforms catalyzed the conversion of T and 11KT into DHT and 11KDHT, respectively, whereas only eel srd5a1 converted T into DHT. DHT and 11KDHT activated eel androgen receptor (ar)α-mediated transactivation as similar fashion to T and 11KT. In contrast, human AR and eel arβ were activated by DHT and11KDHT more strongly than T and 11KT. These results indicate that in teleosts, DHT and 11KDHT may be important 5α-reduced androgens produced in the gonads. In contrast, DHT is the only major 5α-reduced androgens in healthy humans.
Accounting and Management of Natural Resource Consumption Based on Input-Output Method: A Global Bibliometric Analysis
Authors: Wang Siyun , Tang Xu , Zhang Baosheng , Wang Wenhuan
Published: March 2021

Resources and environment management have always been a research hotspot. In the context of sustainable development and environmental governance, scholars and policy makers have been increasing their research efforts on natural resource utilization and its environmental impact. By using the Web of Science Core Collection database, this article applies the bibliometric method to accomplish a systematic review about studies on accounting and management of natural resource consumption based on input-output method. The results indicate that both in terms of the quantity and quality of academic achievements and international cooperation, China is in high academic position and has made great contributions to the development in this research field. While energy and water account for a large proportion of the study objects, more attention is paid on the other kinds of natural resources, such as land, metal, and ocean. International trade is an eternal hot topic in this field. With the continuous progress of the multi-regional input-output model, the importance and feasibility in the analysis of sub-national level or region in the global supply chain gradually emerged. Combining input-output model with other methods can obtain more comprehensive and accurate results for scientific decision-making. Meanwhile, the uncertainty and limitations inherent in such models clearly need further attention.
Improved Sensing Properties of Thermal Conductivity-Type CO2 Gas Sensors by Loading Multi-Walled Carbon Nanotubes Into Nano-Al2O3 Powders
Authors: Shen Bin , Zhang Fang , Jiang Leiming , Liu Xinlei , Song Xiaoyang , Qin Xianli , Li Xuewei
Published: March 2021

Response time is the key index of on-line monitoring system. To improve the response speed of traditional bead thermal conductivity CO2 sensor, this paper proposes to use multi-walled carbon nanotubes (MWCNTs) to improve the performance of gas sensor carrier. Nano-sized γ-Al2O3/CeO2 powder was synthesized by chemical precipitation method under the action of ultrasonic wave. SEM morphology reveals a particle size of 20–50 nm. MWCNTs were hydroxylated and the solution was then prepared by adding a certain amount of dispersant under ultrasonic wave. The composite support of γ- Al2O3/CeO2/MWCNTs was prepared by wet mixing carbon nanotube solution into the above support materials. Using dynamic resistance matching and black component technology, the influence of radiation heat and environmental temperature and humidity is reduced. Results show that the designed thermal conductivity sensor has consistent response and recovery time to different concentrations of CO2, with a T90 response time of 9 s and a T90 recovery time of 13 s, which is faster compared to major commercial Carbon dioxide sensors. The average sensitivity of the sensor is 0.0075 V/10% CO2. Therefore, the high thermal conductivity and pore characteristics of carbon nanotubes can effectively improve the response speed of the thermal conductivity sensor.
Mechanisms and Product Options of Magnesiothermic Reduction of Silica to Silicon for Lithium-Ion Battery Applications
Authors: Tan Yu , Jiang Tingting , Chen George Z.
Published: March 2021

Lithium-ion batteries (LIBs) have been one of the most predominant rechargeable power sources due to their high energy/power density and long cycle life. As one of the most promising candidates for the new generation negative electrode materials in LIBs, silicon has the advantages of high specific capacity, a lithiation potential range close to that of lithium deposition, and rich abundance in the earth’s crust. However, the commercial use of silicon in LIBs is still limited by the short cycle life and poor rate performance due to the severe volume change during Li++ insertion/extraction, as well as the unsatisfactory conduction of electron and Li+ through silicon matrix. Therefore, many efforts have been made to control and stabilize the structures of silicon. Magnesiothermic reduction has been extensively demonstrated as a promising process for making porous silicon with micro- or nanosized structures for better electrochemical performance in LIBs. This article provides a brief but critical overview of magnesiothermic reduction under various conditions in several aspects, including the thermodynamics and mechanism of the reaction, the influences of the precursor and reaction conditions on the dynamics of the reduction, and the interface control and its effect on the morphology as well as the final performance of the silicon. These outcomes will bring about a clearer vision and better understanding on the production of silicon by magnesiothermic reduction for LIBs application.
Security Regional Division of Farmland Soil Heavy Metal Elements in North of the North China Plain
Authors: Kong Chenchen , Zhang Shiwen
Published: March 2021

A total of 94 soil samples from different soil depths (0∼25 cm, 25∼50 cm) were collected of farmland soil around the plain of Beijing, and the concentrations of five heavy metal elements (Cd, Cr, Pb, As, and Hg) were measured using standard methods. The safety utilization evaluation method of heavy metals was based on three different evaluation methods. Then, the governance principles and specific management control strategy were determined in detail according to the core pollution source analysis of each safety grade zone. The results show that there are four different comprehensive safe utilization areas: safe, low-risk, medium-risk, and high-risk utilization. Among them, the study area was dominated by low-risk utilization areas, and the risk trend was gradually weakening from the center of the city to the periphery. Based on the characteristics of different security zones, this study puts on the governance principles of priority protection, long-term monitoring and moderate optimization, strengthens early warning, and cooperates with effective repair and priority governance. And then it puts forward practical control strategies according to the core pollution sources of each safety utilization zone. Our findings may provide a clear direction for rational utilization of land resources and renovation in the future.
The Promise and the Hope of Gene Therapy
Authors: Papanikolaou Eleni , Bosio Andreas
Published: March 2021

It has been over 30 years since visionary scientists came up with the term “Gene Therapy,” suggesting that for certain indications, mostly monogenic diseases, substitution of the missing or mutated gene with the normal allele via gene addition could provide long-lasting therapeutic effect to the affected patients and consequently improve their quality of life. This notion has recently become a reality for certain diseases such as hemoglobinopathies and immunodeficiencies and other monogenic diseases. However, the therapeutic wave of gene therapies was not only applied in this context but was more broadly employed to treat cancer with the advent of CAR-T cell therapies. This review will summarize the gradual advent of gene therapies from bench to bedside with a main focus on hemopoietic stem cell gene therapy and genome editing and will provide some useful insights into the future of genetic therapies and their gradual integration in the everyday clinical practice.
Genetic Features of Reproductive Traits in Bovine and Buffalo: Lessons From Bovine to Buffalo
Authors: Shao Baoshun , Sun Hui , Ahmad Muhammad Jamil , Ghanem Nasser , Abdel-Shafy Hamdy , Du Chao , Deng Tingxian , Mansoor Shahid , Zhou Yang , Yang Yifen , Zhang Shujun , Yang Liguo , Hua Guohua
Published: March 2021

Bovine and buffalo are important livestock species that have contributed to human lives for more than 1000 years. Improving fertility is very important to reduce the cost of production. In the current review, we classified reproductive traits into three categories: ovulation, breeding, and calving related traits. We systematically summarized the heritability estimates, molecular markers, and genomic selection (GS) for reproductive traits of bovine and buffalo. This review aimed to compile the heritability and genome-wide association studies (GWASs) related to reproductive traits in both bovine and buffalos and tried to highlight the possible disciplines which should benefit buffalo breeding. The estimates of heritability of reproductive traits ranged were from 0 to 0.57 and there were wide differences between the populations. For some specific traits, such as age of puberty (AOP) and calving difficulty (CD), the majority beef population presents relatively higher heritability than dairy cattle. Compared to bovine, genetic studies for buffalo reproductive traits are limited for age at first calving and calving interval traits. Several quantitative trait loci (QTLs), candidate genes, and SNPs associated with bovine reproductive traits were screened and identified by candidate gene methods and/or GWASs. The IGF1 and LEP pathways in addition to non-coding RNAs are highlighted due to their crucial relevance with reproductive traits. The distribution of QTLs related to various traits showed a great differences. Few GWAS have been performed so far on buffalo age at first calving, calving interval, and days open traits. In addition, we summarized the GS studies on bovine and buffalo reproductive traits and compared the accuracy between different reports. Taken together, GWAS and candidate gene approaches can help to understand the molecular genetic mechanisms of complex traits. Recently, GS has been used extensively and can be performed on multiple traits to improve the accuracy of prediction even for traits with low heritability, and can be combined with multi-omics for further analysis.
Multimorbidity, Trauma Exposure, and Frailty of Older Adults in the Community
Authors: Papathanasiou Ioanna V. , Fradelos Evangelos C. , Mantzaris Dimitrios , Rammogianni Anna , Malli Foteini , Papagiannis Dimitrios , Gourgoulianis Konstantinos I.
Published: March 2021

The aim of this study is to investigate the relation between multimorbidity, traumatic events and frailty among older adults in the community. The studied population consisted of 257 older people who were recipients of the services and active members of Open Care Centers for the Elderly (OCCE) of the Municipality of Grevena and meet a set of selection criteria. The collection of the data was carried out using a fully structured questionnaire, which consisted of two sections: a form of individual features and the Tilburg Frailty Indicator (TFI). The sample consisted of 114 men (44.4%) and 143 women (55.6%) aged between 61 and 96 years with an average of 75.12 years. The results showed that the mean scores were 2.70 for the Physical Frailty (standard deviation = 2.16), 1.43 for the Psychological Frailty (standard deviation = 1.21), 1.32 for the Social Frailty (standard deviation = 0.64) and 5.44 for the total Frailty (standard deviation = 3.02). We took into account the cut-off point five of 54.1% (n = 139) in terms of the participants’ frailty. Physical, Psychological, and Total Frailty are related to (a) the presence of two or more chronic diseases or disorders, (b) the experience of a serious illness in the previous year, and (c) the experience of a serious illness of a loved one during the previous year. The outcomes helped to identify frailty syndrome in older people and the factors associated with it.
DEEPsc: A Deep Learning-Based Map Connecting Single-Cell Transcriptomics and Spatial Imaging Data
Authors: Maseda Floyd , Cang Zixuan , Nie Qing
Published: March 2021

Single-cell RNA sequencing (scRNA-seq) data provides unprecedented information on cell fate decisions; however, the spatial arrangement of cells is often lost. Several recent computational methods have been developed to impute spatial information onto a scRNA-seq dataset through analyzing known spatial expression patterns of a small subset of genes known as a reference atlas. However, there is a lack of comprehensive analysis of the accuracy, precision, and robustness of the mappings, along with the generalizability of these methods, which are often designed for specific systems. We present a system-adaptive deep learning-based method (DEEPsc) to impute spatial information onto a scRNA-seq dataset from a given spatial reference atlas. By introducing a comprehensive set of metrics that evaluate the spatial mapping methods, we compare DEEPsc with four existing methods on four biological systems. We find that while DEEPsc has comparable accuracy to other methods, an improved balance between precision and robustness is achieved. DEEPsc provides a data-adaptive tool to connect scRNA-seq datasets and spatial imaging datasets to analyze cell fate decisions. Our implementation with a uniform API can serve as a portal with access to all the methods investigated in this work for spatial exploration of cell fate decisions in scRNA-seq data. All methods evaluated in this work are implemented as an open-source software with a uniform interface.
Peripheral Nervous System Involvement in Sjögren’s Syndrome: Analysis of a Cohort From the Italian Research Group on Sjögren’s Syndrome
Authors: Cafaro Giacomo , Perricone Carlo , Carubbi Francesco , Baldini Chiara , Quartuccio Luca , Priori Roberta , Berardicurti Onorina , Ferro Francesco , Gandolfo Saviana , Gattamelata Angelica , Giacomelli Roberto , De Vita Salvatore , Gerli Roberto , Bartoloni Elena
Published: March 2021

Purpose

The prevalence of peripheral nervous system (PNS) involvement in primary Sjögren’s syndrome (pSS) has been reported to range from 2% to over 50%. Bias in study designs, including low number of patients and unclearly defined rheumatological and neurological diagnosis could explain such variability. Consequently, the exact depiction of PNS involvement in pSS is still lacking. This study aimed at analyzing the prevalence and the clinical and laboratory factors associated with PNS involvement in a very large cohort of well-characterized pSS patients with a clearly defined neurological diagnosis.

Methods

Clinical and serological data of 1,695 pSS patients with specific and accurate information on PNS involvement were analyzed. Comparisons between patients with and without PNS involvement and between patients with distinct subsets of PNS manifestations were performed.

Results

Prevalence of PNS involvement was 3.7%. The most frequent types observed were pure sensory neuropathies and axonal sensorimotor polyneuropathies (SMP). Patients with PNS involvement exhibited a more active disease profile and were more frequently treated with immunosuppressants. Intriguingly, clinical and serological negative prognostic factors, including purpura, extra-glandular manifestations, leukopenia, low complement and cryoglobulinemia, principally characterized patients with SMP, while subjects with pure sensory neuropathy displayed a milder phenotype.

Conclusion

Our results highlight that PNS involvement is rather rare, but prognostically relevant in pSS. Main adverse prognostic features characterize patients with SMP, while pure sensory neuropathies are usually associated with a mild clinical picture. These findings, useful for patient stratification, may suggest protean pathogenic pathways underlying different types of PNS manifestations in pSS.
A Phase II Randomized Clinical Trial and Mechanistic Studies Using Improved Probiotics to Prevent Oral Mucositis Induced by Concurrent Radiotherapy and Chemotherapy in Nasopharyngeal Carcinoma
Authors: Xia Chaofei , Jiang Chunling , Li Wenyu , Wei Jing , Hong Hu , Li Jingao , Feng Liu , Wei Hong , Xin Hongbo , Chen Tingtao
Published: March 2021

Earlier evidence has proven that probiotic supplements can reduce concurrent chemoradiotherapy (CCRT)-induced oral mucositis (OM) in nasopharyngeal cancer (NPC). The incidence of severe OM (grade 3 or higher) was the primary endpoint in this study. We first enrolled 85 patients with locally advanced NPC who were undergoing CCRT. Of them, 77 patients were finally selected and randomized (1:1) to receive either a probiotic cocktail or placebo. To investigate the protective effects and the mechanism of probiotic cocktail treatment on OM induced by radiotherapy and chemotherapy, we randomly divided the rats into the control (C) group, the model (M) group, and the probiotic (P) group. After treatment, samples from the tongue, blood, and fecal and proximal colon tissues on various days (7th, 14th, and 21st days) were collected and tested for the inflammatory response, cell apoptosis, intestinal permeability, and intestinal microbial changes. We found that patients taking the probiotic cocktail showed significantly lower OM. The values of the incidence of 0, 1, 2, 3, and 4 grades of OM in the placebo group and in the probiotic cocktail group were reported to be 0, 14.7, 38.2, 32.4, and 14.7% and 13.9, 36.1, 25, 22.2, and 2.8%, respectively. Furthermore, patients in the probiotic cocktail group showed a decrease in the reduction rate of CD3+ T cells (75.5% vs. 81%, p < 0.01), CD4+ T cells (64.53% vs. 79.53%, p < 0.01), and CD8+ T cells (75.59 vs. 62.36%, p < 0.01) compared to the placebo group. In the rat model, the probiotic cocktail could ameliorate the severity of OM, decrease the inflammatory response, cause cell apoptosis and intestinal permeability, and restore the structure of gut microbiota to normalcy. In conclusion, the modified probiotic cocktail significantly reduces the severity of OM by enhancing the immune response of patients with NPC and modifying the structure of gut microbiota.

Clinical Trial Registration: The Clinical Trial Registration should be the NCT03112837.
The Effects of Helicobacter pylori Infection on Microbiota Associated With Gastric Mucosa and Immune Factors in Children
Authors: Zheng Wei , Miao Jing , Luo Lingling , Long Gao , Chen Bo , Shu Xiaoli , Gu Weizhong , Peng Kerong , Li Fubang , Zhao Hong , Botchway Benson O. A. , Fang Marong , Jiang Mizu
Published: March 2021

Background

Helicobacter pylori infection is the main cause of chronic gastritis in children. Little is known about the effect of Helicobacter pylori on microbiota and immunity. This study was aimed at characterizing stomach microbiota and immune-regulatory properties of children with Helicobacter pylori colonization.

Methods

We studied 122 children who had undergone gastric endoscopy due to gastrointestinal symptoms, 57 were diagnosed with Helicobacter pylori infection. Endoscopic mucosal biopsy samples were obtained for DNA and RNA extraction. Microbiomes were analyzed by 16S rRNA profiling, with the differentially expressed genes analyzed using RNA sequencing. The RNA-sequencing results of selected genes were validated by qRT-PCR.

Results

Bacterial diversity of Helicobacter pylori-positive gastric specimens were lower than those of negative, and both groups were clearly separated according to beta diversity. Helicobacter pylori-positive group significantly reduced proportions of six phyla and eight genera; only Helicobacter taxa were more abundant in Helicobacter pylori-negative group. Gastric tissues RNA sequencing showed increased expression of multiple immune response genes in Helicobacter pylori -infection. Helicobacter pylori -infected children with restructured gastric microbiota had higher levels of FOXP3, IL-10, TGF-β1 and IL-17A expressions, which were consistent with increased CD4+T cell and macrophagocyte, compared with non-infected children.

Conclusions

Presence of Helicobacter pylori significantly influences gastric microbiota and results in lower abundance of multiple taxonomic levels in children. Meanwhile, it affects gastric immune environment and promotes the occurrence of gastritis.

Clinical Trial Registration

[http://www.chictr.org.cn], identifier [ChiCTR1800015190]
The CD28-Transmembrane Domain Mediates Chimeric Antigen Receptor Heterodimerization With CD28
Authors: Muller Yannick D. , Nguyen Duy P. , Ferreira Leonardo M. R. , Ho Patrick , Raffin Caroline , Valencia Roxxana Valeria Beltran , Congrave-Wilson Zion , Roth Theodore L. , Eyquem Justin , Van Gool Frederic , Marson Alexander , Perez Laurent , Wells James A. , Bluestone Jeffrey A. , Tang Qizhi
Published: March 2021

Anti-CD19 chimeric antigen receptor (CD19-CAR)-engineered T cells are approved therapeutics for malignancies. The impact of the hinge domain (HD) and the transmembrane domain (TMD) between the extracellular antigen-targeting CARs and the intracellular signaling modalities of CARs has not been systemically studied. In this study, a series of 19-CARs differing only by their HD (CD8, CD28, or IgG4) and TMD (CD8 or CD28) was generated. CARs containing a CD28-TMD, but not a CD8-TMD, formed heterodimers with the endogenous CD28 in human T cells, as shown by co-immunoprecipitation and CAR-dependent proliferation of anti-CD28 stimulation. This dimerization was dependent on polar amino acids in the CD28-TMD and was more efficient with CARs containing CD28 or CD8 HD than IgG4-HD. The CD28-CAR heterodimers did not respond to CD80 and CD86 stimulation but had a significantly reduced CD28 cell-surface expression. These data unveiled a fundamental difference between CD28-TMD and CD8-TMD and indicated that CD28-TMD can modulate CAR T-cell activities by engaging endogenous partners.
PNOC Expressed by B Cells in Cholangiocarcinoma Was Survival Related and LAIR2 Could Be a T Cell Exhaustion Biomarker in Tumor Microenvironment: Characterization of Immune Microenvironment Combining Single-Cell and Bulk Sequencing Technology
Authors: Chen Zheng , Yu Mincheng , Yan Jiuliang , Guo Lei , Zhang Bo , Liu Shuang , Lei Jin , Zhang Wentao , Zhou Binghai , Gao Jie , Yang Zhangfu , Li Xiaoqiang , Zhou Jian , Fan Jia , Ye Qinghai , Li Hui , Xu Yongfeng , Xiao Yongsheng
Published: March 2021

Background

Cholangiocarcinoma was a highly malignant liver cancer with poor prognosis, and immune infiltration status was considered an important factor in response to immunotherapy. In this investigation, we tried to locate immune infiltration related genes of cholangiocarcinoma through combination of bulk-sequencing and single-cell sequencing technology.

Methods

Single sample gene set enrichment analysis was used to annotate immune infiltration status in datasets of TCGA CHOL, GSE32225, and GSE26566. Differentially expressed genes between high- and low-infiltrated groups in TCGA dataset were yielded and further compressed in other two datasets through backward stepwise regression in R environment. Single-cell sequencing data of GSE138709 was loaded by Seurat software and was used to examined the expression of infiltration-related gene set. Pathway changes in malignant cell populations were analyzed through scTPA web tool.

Results

There were 43 genes differentially expressed between high- and low-immune infiltrated patients, and after further compression, PNOC and LAIR2 were significantly correlated with high immune infiltration status in cholangiocarcinoma. Through analysis of single-cell sequencing data, PNOC was mainly expressed by infiltrated B cells in tumor microenvironment, while LAIR2 was expressed by Treg cells and partial GZMB+ CD8 T cells, which were survival related and increased in tumor tissues. High B cell infiltration levels were related to better overall survival. Also, malignant cell populations demonstrated functionally different roles in tumor progression.

Conclusion

PNOC and LAIR2 were biomarkers for immune infiltration evaluation in cholangiocarcinoma. PNOC, expressed by B cells, could predict better survival of patients, while LAIR2 was a potential marker for exhaustive T cell populations, correlating with worse survival of patients.
COVID-19 and HIV-Associated Immune Reconstitution Inflammatory Syndrome: Emergence of Pathogen-Specific Immune Responses Adding Fuel to the Fire
Authors: Seddiki Nabila , French Martyn
Published: March 2021

Both coronavirus disease 2019 (COVID-19) and mycobacterial immune reconstitution inflammatory syndrome (IRIS) in patients with HIV-1 infection result from immunopathology that is characterized by increased production of multiple pro-inflammatory chemokines and cytokines associated with activation of myeloid cells (monocytes, macrophages and neutrophils). We propose that both conditions arise because innate immune responses generated in the absence of effective adaptive immune responses lead to monocyte/macrophage activation that is amplified by the emergence of a pathogen-specific adaptive immune response skewed towards monocyte/macrophage activating activity by the immunomodulatory effects of cytokines produced during the innate response, particularly interleukin-18. In mycobacterial IRIS, that disease-enhancing immune response is dominated by a Th1 CD4+T cell response against mycobacterial antigens. By analogy, it is proposed that in severe COVID-19, amplification of monocyte/macrophage activation results from the effects of a SARS-CoV-2 spike protein antibody response with pro-inflammatory characteristics, including high proportions of IgG3 and IgA2 antibodies and afucosylation of IgG1 antibodies, that arises from B cell differentiation in an extra-follicular pathway promoted by activation of mucosa-associated invariant T cells. We suggest that therapy for the hyperinflammation underlying both COVID-19 and mycobacterial IRIS might be improved by targeting the immunomodulatory as well as the pro-inflammatory effects of the ‘cytokine storm’.
Co-Immunization With CHIKV VLP and DNA Vaccines Induces a Promising Humoral Response in Mice
Authors: Zhao Zhimin , Deng Yao , Niu Peihua , Song Jingdong , Wang Wen , Du Yongping , Huang Baoying , Wang Wenling , Zhang Leiliang , Zhao Ping , Tan Wenjie
Published: March 2021

Chikungunya fever is an acute infectious disease that is mediated by the mosquito-transmitted chikungunya virus (CHIKV), for which no licensed vaccines are currently available. Here, we explored several immunization protocols and investigated their immunity and protective effects in mice, with DNA- and virus-like particle (VLP)- vaccines, both alone and in combination. Both DNA and VLP vaccine candidates were developed and characterized, which express CHIKV structural genes (C-E3-E2-6K-E1). Mice were immunized twice, with different protocols, followed by immunological detection and CHIKV Ross challenge. The highest antigen-specific IgG and neutralizing activity were induced by DNA and VLP co-immunization, while the highest cellular immunity was induced by DNA vaccination alone. Although all vaccine groups could protect mice from lethal CHIKV challenge, demonstrated as reduced viral load in various tissues, without weight loss, mice co-immunized with DNA and VLP exhibited the mildest histopathological changes and lowest International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) scores, in comparison to mice with either DNA or VLP vaccination alone. We concluded that co-immunization with DNA and VLP is a promising strategy to inducing better protective immunity against CHIKV infection.
Marine Citizen Science: Current State in Europe and New Technological Developments
Authors: Garcia-Soto Carlos , Seys Jan J. C. , Zielinski Oliver , Busch J. A. , Luna S. I. , Baez Jose Carlos , Domegan C. , Dubsky K. , Kotynska-Zielinska I. , Loubat P. , Malfatti Francesca , Mannaerts G. , McHugh Patricia , Monestiez P. , van der Meeren Gro I. , Gorsky G.
Published: March 2021

Marine citizen science is emerging with promising opportunities for science, policy and public but there is still no comprehensive overview of the current state in Europe. Based on 127 projects identified for the North Sea area we estimate there might be as much as 500 marine and coastal citizen science projects running in Europe, i.e., one marine citizen science project per ∼85 km of coastline, with an exponential growth since 1990. Beach-based projects are more accessible and hence most popular (60% of the projects), and the mean duration of the projects is 18–20 years. Current trends, topics, organizers, aims, and types of programme in terms of participation are presented in this overview. Progress in marine citizen science is specially enabled and promoted through technological developments. Recent technological advances and best practise examples are provided here, untapping the potential of smart mobile apps, do-it-yourself (DIY) technologies, drones, and artificial intelligence (AI) web services.
Advanced Biomimetic Nanomaterials for Non-invasive Disease Diagnosis
Authors: Feng Zhiyuan , Fan Hao , Cheng Lin , Zhang Huan , Fan Hong , Liu Jia
Published: March 2021

In modern society, the incidence of cancer, inflammatory diseases, nervous system diseases, metabolic diseases, and cardiovascular diseases is on the rise. These diseases not only cause physical and mental suffering for patients, but also place an enormous burden on society. Early, non-invasive diagnosis of these diseases can reduce the physical and mental pain of patients and social stress. There is an urgent need for advanced materials and methods for non-invasive disease marker detection, large-scale disease screening, and early diagnosis. Biomimetic medical materials are synthetic materials designed to be biocompatible or biodegradable, then developed for use in the medical industry. In recent years, with the development of nanotechnology, a variety of biomimetic medical materials with advanced properties have been introduced. Biomimetic nanomaterials have made great progress in biosensing, bioimaging, and other fields. The latest advance of biomimetic nanomaterials in disease diagnosis has attracted tremendous interest. However, the application of biomimetic nanomaterials in disease diagnosis has not been reviewed. This review particularly focuses on the potential of biomimetic nanomaterials in non-invasive disease marker detection and disease diagnosis. The first part focuses on the properties and characteristics of different kinds of advanced biomimetic nanomaterials. In the second part, the recent cutting-edge methods using biosensors and bioimaging based on biomimetic nanomaterials for non-invasive disease diagnosis are reviewed. In addition, the existing problems and future development of biomimetic nanomaterials is briefly described in the third part. The application of biomimetic nanomaterials would provide a novel and promising diagnostic method for non-invasive disease marker detection, large-scale clinical screening, and diagnosis, promoting the exploitation of devices with better detection performance and the development of global clinical public health.
Case Report: Molecular Diagnosis of Fungal Keratitis Associated With Contact Lenses Caused by Fusarium solani
Authors: Trovato Laura , Marino Antonio , Pizzo Giovanni , Oliveri Salvatore
Published: March 2021

Fusarium is a filamentous fungus commonly found in the environment and is the major cause of fungal keratitis. We report a case of keratomycosis caused by Fusarium solani in a patient using disposable soft contact lenses. A delay in diagnosis led to the initiation of an empirical antifungal treatment with the subsequent deterioration of the patient's clinical condition. The use of the real-time quantitative PCR assay confirmed keratitis from F. solani providing a result in <48 h and therefore giving the possibility of quickly starting targeted antifungal therapy. The patient had an improvement in eye condition after the diagnosis of keratitis by F. solani and the rapid change to targeted antifungal treatment. For the rapid identification of corneal fungal pathogens, we believe that PCR may be added for the diagnosis of mycotic keratitis pending the isolation in culture that is necessary for in vitro susceptibility testing.
Management of Unsatisfactory Postoperative Double Eyelid With Intralesional Corticosteroid Injection
Authors: Zhang Siyi , Zhou Yixiong , Yu Fei , Yan Dan , Yan Yan , Zhou Meng , Fu Yao , Lu Yang
Published: March 2021

Purpose: The present study was designed to observe the curative effect of early intralesional corticosteroid injection to treat unsatisfactory double eyelid.

Methods: This retrospective, observational study included 30 female patients (age 22–35 years) receiving intralesional corticosteroid injection after complaining about the unsatisfactory double eyelid post-transcutaneous upper eyelid blepharoplasty. The postoperative double eyelid anomalies included multiple folds, sunken eyelids, and severe postoperative eyelid edema. The evaluation of the clinical effect was based on the bilateral symmetry of the eyelid, the placement of the lid fold, the radian of the double eyelid, and the extent of the swelling and depression.

Results: Multiple folds were observed in 11 (36.67%) patients, sunken eyelids in 9 (30.00%) patients, and severe postoperative eyelid edema in 10 (33.33%) patients. Among them, 17 (56.67%) patients received one intralesional injection and experienced significant improvement in the eyelid, while 8 (26.67%) accepted another injection at 1 month after the first injection and achieved marked improvement. The remaining 5 (16.67%) patients were dissatisfied with the results and might need further repair surgery: 2 patients had multiple folds, 2 showed postoperative edema, and 1 presented sunken eyelids. None of the patients reported any adverse reactions.

Conclusion: Intralesional corticosteroid injection for the correction of the postoperative unsatisfactory double eyelid is safe and convenient, and provides a novel method for early intervention.
Implementation of Pharmacogenomic Information on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Authors: Tsukagoshi Eri , Tanaka Yoichi , Saito Yoshiro
Published: March 2021

Drug-related Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare but severe adverse drug reactions, termed as idiosyncratic reactions; however, predicting their onset remains challenging. Pharmacogenomic information associated with SJS/TEN has accumulated on several drugs in the last 15 years, with clinically useful information now included on drug labels in several countries/regions or guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC) for implementation. However, label information might be different among countries. This mini-review summarizes pharmacogenomic information on drug labels of five drugs in six countries and compared descriptions of drug labels and CPIC guidelines. Finally, we discuss future perspectives of this issue. Pharmacogenomic information on drug labels is not well-harmonized across countries/regions, but CPIC guidelines are a scientifically sound goal for future pharmacogenomic implementation.
Ross River Virus Immune Evasion Strategies and the Relevance to Post-viral Fatigue, and Myalgic Encephalomyelitis Onset
Authors: Lidbury Brett A.
Published: March 2021

Ross River virus (RRV) is an endemic Australian arbovirus, and member of the Alphavirus family that also includes Chikungunya virus (CHIK). RRV is responsible for the highest prevalence of human disease cases associated with mosquito-borne transmission in Australia, and has long been a leading suspect in cases of post-viral fatigue syndromes, with extrapolation of this link to Myalgic Encephalomyelitis (ME). Research into RRV pathogenesis has revealed a number of immune evasion strategies, impressive for a virus with a genome size of 12 kb (plus strand RNA), which resonate with insights into viral pathogenesis broadly. Drawing from observations on RRV immune evasion, mechanisms of relevance to long term idiopathic fatigue are featured as a perspective on infection and eventual ME symptoms, which include considerations of; (1) selective pro-inflammatory gene suppression post antibody-dependent enhancement (ADE) of RRV infection, (2) Evidence from other virus families of immune disruption and evasion post-ADE, and (3) how virally-driven immune evasion may impact on mitochondrial function via target of rapamycin (TOR) complexes. In light of these RRV measures to counter the host immune - inflammatory responses, links to recent discoveries explaining cellular, immune and metabolomic markers of ME will be explored and discussed, with the implications for long-COVID post SARS-CoV-2 also considered. Compelling issues on the connections between virally-induced alterations in cytokine expression, for example, will be of particular interest in light of energy pathways, and how these perturbations manifest clinically.
The Archaeal Elongation Factor EF-2 Induces the Release of aIF6 From 50S Ribosomal Subunit
Authors: Lo Gullo Giada , De Santis Maria Luisa , Paiardini Alessandro , Rosignoli Serena , Romagnoli Alice , La Teana Anna , Londei Paola , Benelli Dario
Published: March 2021

The translation factor IF6 is a protein of about 25 kDa shared by the Archaea and the Eukarya but absent in Bacteria. It acts as a ribosome anti-association factor that binds to the large subunit preventing the joining to the small subunit. It must be released from the large ribosomal subunit to permit its entry to the translation cycle. In Eukarya, this process occurs by the coordinated action of the GTPase Efl1 and the docking protein SBDS. Archaea do not possess a homolog of the former factor while they have a homolog of SBDS. In the past, we have determined the function and ribosomal localization of the archaeal (Sulfolobus solfataricus) IF6 homolog (aIF6) highlighting its similarity to the eukaryotic counterpart. Here, we analyzed the mechanism of aIF6 release from the large ribosomal subunit. We found that, similarly to the Eukarya, the detachment of aIF6 from the 50S subunit requires a GTPase activity which involves the archaeal elongation factor 2 (aEF-2). However, the release of aIF6 from the 50S subunits does not require the archaeal homolog of SBDS, being on the contrary inhibited by its presence. Molecular modeling, using published structural data of closely related homologous proteins, elucidated the mechanistic interplay between the aIF6, aSBDS, and aEF2 on the ribosome surface. The results suggest that a conformational rearrangement of aEF2, upon GTP hydrolysis, promotes aIF6 ejection. On the other hand, aSBDS and aEF2 share the same binding site, whose occupation by SBDS prevents aEF2 binding, thereby inhibiting aIF6 release.
Forensic Microbiome Database: A Tool for Forensic Geolocation Meta-Analysis Using Publicly Available 16S rRNA Microbiome Sequencing
Authors: Singh Harinder , Clarke Thomas , Brinkac Lauren , Greco Chris , Nelson Karen E.
Published: March 2021

The human microbiome has been proposed as a tool to investigate different forensic questions, including for the identification of multiple personal information. However, the fragmented state of the publicly available data has retarded the development of analysis techniques and, therefore, the implementation of microbiomes as a forensic tool. To address this, we introduce the forensic microbiome database (FMD), which is a collection of 16S rRNA data and associated metadata generated from publicly available data. The raw data was further normalized and processed using a pipeline to create a standardized data set for downstream analysis. We present a website allowing for the exploration of geolocation signals in the FMD. The website allows users to investigate the taxonomic differences between microbiomes harvested from different locations and to predict the geolocation of their data based on the FMD sequences. All the results are presented in dynamic graphics to allow for a rapid and intuitive investigation of the taxonomic distributions underpinning the geolocation signals and prediction between locations. Apart from the forensic aspect, the database also allows exploration and comparison of microbiome samples from different geolocation and between different body sites. The goal of the FMD is to provide the scientific and non-scientific communities with data and tools to explore the possibilities of microbiomes to answer forensic questions and serve as a model for any future such databases.1
Preferential Neuronal Responses to Snakes in the Monkey Medial Prefrontal Cortex Support an Evolutionary Origin for Ophidiophobia
Authors: Dinh Ha Trong , Nishimaru Hiroshi , Le Quan Van , Matsumoto Jumpei , Setogawa Tsuyoshi , Maior Rafael S. , Tomaz Carlos , Ono Taketoshi , Nishijo Hisao
Published: March 2021

Ophidiophobia (snake phobia) is one of the most common specific phobias. It has been proposed that specific phobia may have an evolutionary origin, and that attentional bias to specific items may promote the onset of phobia. Noninvasive imaging studies of patients with specific phobia reported that the medial prefrontal cortex (mPFC), especially the rostral part of the anterior cingulate cortex (rACC), and amygdala are activated during the presentation of phobogenic stimuli. We propose that the mPFC-amygdala circuit may be involved in the pathogenesis of phobia. The mPFC receives inputs from the phylogenically old subcortical visual pathway including the superior colliculus, pulvinar, and amygdala, while mPFC neurons are highly sensitive to snakes that are the first modern predator of primates, and discriminate snakes with striking postures from those with non-striking postures. Furthermore, the mPFC has been implicated in the attentional allocation and promotes amygdala-dependent aversive conditioning. These findings suggest that the rACC focuses attention on snakes, and promotes aversive conditioning to snakes, which may lead to anxiety and ophidiophobia.
TuberOus SClerosis registry to increAse disease awareness (TOSCA) Post-Authorisation Safety Study of Everolimus in Patients With Tuberous Sclerosis Complex
Authors: Kingswood J. Chris , Belousova Elena , Benedik Mirjana P. , Budde Klemens , Carter Tom , Cottin Vincent , Curatolo Paolo , Dahlin Maria , D'Amato Lisa , d'Augères Guillaume B. , de Vries Petrus J. , Ferreira José C. , Feucht Martha , Fladrowski Carla , Hertzberg Christoph , Jozwiak Sergiusz , Lawson John A. , Macaya Alfons , Marques Ruben , Nabbout Rima , O'Callaghan Finbar , Qin Jiong , Sander Valentin , Sauter Matthias , Shah Seema , Takahashi Yukitoshi , Touraine Renaud , Youroukos Sotiris , Zonnenberg Bernard , Jansen Anna C. ,   TOSCA Consortium and TOSCA Investigators
Published: March 2021

This non-interventional post-authorisation safety study (PASS) assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) who participated in the TuberOus SClerosis registry to increase disease Awareness (TOSCA) clinical study and received everolimus for the licensed indications in the European Union. The rate of adverse events (AEs), AEs that led to dose adjustments or treatment discontinuation, AEs of potential clinical interest, treatment-related AEs (TRAEs), serious AEs (SAEs), and deaths were documented. One hundred seventy-nine patients were included in the first 5 years of observation; 118 of 179 patients had an AE of any grade, with the most common AEs being stomatitis (7.8%) and headache (7.3%). AEs caused dose adjustments in 56 patients (31.3%) and treatment discontinuation in nine patients (5%). AEs appeared to be more frequent and severe in children. On Tanner staging, all patients displayed signs of age-appropriate sexual maturation. Twenty-two of 106 female (20.8%) patients had menstrual cycle disorders. The most frequent TRAEs were stomatitis (6.7%) and aphthous mouth ulcer (5.6%). SAEs were reported in 54 patients (30.2%); the most frequent SAE was pneumonia (>3% patients; grade 2, 1.1%, and grade 3, 2.8%). Three deaths were reported, all in patients who had discontinued everolimus for more than 28 days, and none were thought to be related to everolimus according to the treating physicians. The PASS sub-study reflects the safety and tolerability of everolimus in the management of TSC in real-world routine clinical practice.