bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of the immune microenvironment and their clinical significance in non-small cell lung cancer patients with ALK-rearranged mutation
Authors: Zhang Bo , Zeng Jingtong , Zhang Hao , Zhu Shuai , Wang Hanqing , He Jinling , Yang Lingqi , Zhou Ning , Zu Lingling , Xu Xiaohong , Song Zuoqing , Xu Song
Published: September 2022

Background

Although immune checkpoint inhibitors (ICIs) are one of the most important treatments for advanced-stage non-small-cell lung cancer (NSCLC), NSCLC patients with ALK-rearranged usually don’t obtain a clinical benefit. The reason may be related to the unique tumor microenvironment (TME). We evaluated the characteristics of immune biomarkers of the TME and their prognostic value in ALK-rearranged NSCLC.

Methods

Tumor samples from patients with ALK-rearranged (N = 39) and EGFR- (N = 40)/KRAS- (N = 30) mutated NSCLC were collected. Immunohistochemistry (IHC) was used to assess the expression of 9 tumor immune markers as well as 6 immune markers of tumor-infiltrating cells. To research the TME of ALK-rearranged NSCLC, EGFR/KRAS-positive patients were used as controls. Furthermore, the correlation between the efficacy and prognosis of patients with advanced-stage (IIIC-IV) ALK rearrangements treated with targeted drugs was analyzed in terms of the TME.

Results

The proportion of PD-L1+ tumors was lower in ALK-positive NSCLC than in KRAS-positive NSCLC. Besides, the proportion of T cells expressing TIM-3-CD8+ (15.38%), CTLA4-CD8+ (12.82%), LAG3-CD8+ (33.33%) and PD-1-CD8+ (2.56%) in ALK-positive NSCLC was lower than that in EGFR/KRAS-positive NSCLC. The expression of CD3, CD8 T cells and CD20 B cells was lower in ALK-positive NSCLC than in KRAS-positive NSCLC (p < 0.0001, < 0.005, and < 0.001, respectively). Nevertheless, the level of CD4 helper T cells was higher in ALK-positive NSCLC than in EGFR/KRAS-positive NSCLC (p < 0.0001 and p < 0.05, respectively). The repression of TIM3 was higher in ALK-positive NSCLC than in KRAS-positive NSCLC (p < 0.001). In addition, our data showed that high expression of PD-L1 (HR = 0.177, 95% CI 0.038–0.852, p = 0.027) and CTLA4 (HR = 0.196, 95% CI 0.041–0.947, p = 0.043) was related to lower OS in advanced-stage ALK- rearranged NSCLC patients treated with ALK tyrosine kinase inhibitors (TKIs).

Conclusions

Immunosuppressive status was characteristic of the TME in patients with ALK-positive NSCLC compared with EGFR/KRAS-positive NSCLC. High expression of PD-L1 and CTLA4 was an adverse prognostic factor in advanced-stage ALK-rearranged NSCLC patients treated with ALK-TKIs. Immunotherapy for ALK-rearranged patients requires further exploration and validation by clinical trials.
Harnessing the immune system by targeting immune checkpoints: Providing new hope for Oncotherapy
Authors: Yu Lu , Sun Minghan , Zhang Qi , Zhou Qiao , Wang Yi
Published: September 2022

With the goal of harnessing the host’s immune system to provide long-lasting remission and cures for various cancers, the advent of immunotherapy revolutionized the cancer therapy field. Among the current immunotherapeutic strategies, immune checkpoint blockades have greatly improved the overall survival rates in certain patient populations. Of note, CTLA4 and PD-1/PD-L1 are two major non-redundant immune checkpoints implicated in promoting cancer immune evasion, and ultimately lead to relapse. Antibodies or inhibitors targeting these two c+heckpoints have achieved some encouraging clinical outcomes. Further, beyond the canonical immune checkpoints, more inhibitory checkpoints have been identified. Herein, we will summarize recent progress in immune checkpoint blockade therapies, with a specific focus on key pre-clinical and clinical results of new immune checkpoint therapies for cancer. Given the crucial roles of immune checkpoint blockade in oncotherapy, drugs targeting checkpoint molecules expressed by both cancer and immune cells are in clinical trials, which will be comprehensively summarized in this review. Taken together, investigating combinatorial therapies targeting immune checkpoints expressed by cancer cells and immune cells will greatly improve immunotherapies that enhance host elimination of tumors.
Harmonization and qualification of an IFN-γ Enzyme-Linked ImmunoSpot assay (ELISPOT) to measure influenza-specific cell-mediated immunity within the FLUCOP consortium
Authors: Waerlop Gwenn , Leroux-Roels Geert , Lambe Teresa , Bellamy Duncan , Medaglini Donata , Pettini Elena , Cox Rebecca Jane , Trieu Mai-Chi , Davies Richard , Bredholt Geir , Montomoli Emanuele , Gianchecchi Elena , Clement Frédéric
Published: September 2022

Influenza continues to be the most important cause of viral respiratory disease, despite the availability of vaccines. Today’s evaluation of influenza vaccines mainly focuses on the quantitative and functional analyses of antibodies to the surface proteins haemagglutinin (HA) and neuraminidase (NA). However, there is an increasing interest in measuring cellular immune responses targeting not only mutation-prone surface HA and NA but also conserved internal proteins as these are less explored yet potential correlates of protection. To date, laboratories that monitor cellular immune responses use a variety of in-house procedures. This generates diverging results, complicates interlaboratory comparisons, and hampers influenza vaccine evaluation. The European FLUCOP project aims to develop and standardize assays for the assessment of influenza vaccine correlates of protection. This report describes the harmonization and qualification of the influenza-specific interferon-gamma (IFN-γ) Enzyme-Linked ImmunoSpot (ELISpot) assay. Initially, two pilot studies were conducted to identify sources of variability during sample analysis and spot enumeration in order to develop a harmonized Standard Operating Procedure (SOP). Subsequently, an assay qualification study was performed to investigate the linearity, intermediate precision (reproducibility), repeatability, specificity, Lower and Upper Limits of Quantification (LLOQ-ULOQ), Limit of Detection (LOD) and the stability of signal over time. We were able to demonstrate that the FLUCOP harmonized IFN-γ ELISpot assay procedure can accurately enumerate IFN-γ secreting cells in the analytical range of 34.4 Spot Forming Units (SFU) per million cells up to the technical limit of the used reader and in the linear range from 120 000 to 360 000 cells per well, in plates stored up to 6 weeks after development. This IFN-γ ELISpot procedure will hopefully become a useful and reliable tool to investigate influenza-specific cellular immune responses induced by natural infection or vaccination and can be an additional instrument in the search for novel correlates of protection.
Sedimentary carbon on the continental shelf: Emerging capabilities and research priorities for Blue Carbon
Authors: Graves Carolyn A. , Benson Lisa , Aldridge John , Austin William E. N. , Dal Molin Franck , Fonseca Vera G. , Hicks Natalie , Hynes Clare , Kröger Silke , Lamb Philip D. , Mason Claire , Powell Claire , Smeaton Craig , Wexler Sarah K. , Woulds Clare , Parker Ruth
Published: September 2022

Continental shelf sediments store large amounts of organic carbon. Protecting this carbon from release back into the marine system and managing the marine environment to maximize its rate of accumulation could both play a role in mitigating climate change. For these reasons, in the context of an expanding “Blue Carbon” concept, research interest in the quantity and vulnerability of carbon stored in continental shelf, slope, and deep ocean sediments is increasing. In these systems, carbon storage is physically distant from carbon sources, altered between source and sink, and disturbed by anthropogenic activities. The methodological approaches needed to obtain the evidence to assess shelf sea sediment carbon manageability and vulnerability within an evolving blue carbon framework cannot be transferred directly from those applied in coastal vegetated “traditional” blue carbon habitats. We present a toolbox of methods which can be applied in marine sediments to provide the evidence needed to establish where and when marine carbon in offshore sediments can contribute to climate mitigation, focusing on continental shelf sediments. These methods are discussed in the context of the marine carbon cycle and how they provide evidence on: (i) stock: how much carbon is there and how is it distributed? (ii) accumulation: how rapidly is carbon being added or removed? and (iii) anthropogenic pressures: is carbon stock and/or accumulation vulnerable to manageable human activities? Our toolbox provides a starting point to inform choice of techniques for future studies alongside consideration of their specific research questions and available resources. Where possible, a stepwise approach to analyses should be applied in which initial parameters are analysed to inform which samples, if any, will provide information of interest from more resource-intensive analyses. As studies increasingly address the knowledge gaps around continental shelf carbon stocks and accumulation – through both sampling and modelling – the management of this carbon with respect to human pressures will become the key question for understanding where it fits within the blue carbon framework and within the climate mitigation discourse.
Kayak Drone – a silent acoustic unmanned surface vehicle for marine research
Authors: Totland Atle , Johnsen Espen
Published: September 2022

Advancements in technologies have led to a rapid development of unmanned surface vehicles (USV) for marine ecosystem monitoring. The design, size, and scientific payload of the USVs differ as they are built for different purposes. Here, we present the design criteria and detailed technical solutions of a prototype USV which has been built to fulfill the following experimental and operational needs; the USV should be used for inshore and shallow water acoustic monitoring, offshore comparison of echo sounder recordings from the USV and research vessels, monitor natural fish schooling behavior and seabird-fish behavioral interactions. The prototype has been built over a period of 5 years with steadily quality improvements. As the hull is based on an expedition double kayak, the USV is named Kayak Drone, and we aimed at building the Kayak Drone using of-the-shelf hardware and existing open-source software. This allowed for the development of a modular and well-functioning USV at a relatively low cost. The Kayak Drone produces very little noise and in situ experiments show that the Kayak Drone can record echo sounder data of fish near the surface without disturbing their natural distribution and behavior. One in situ study shows that the Kayak Drone could navigate within a couple of meters from swimming puffin and other seabirds without triggering escape. These results demonstrate that the Kayak Drone can be utilized to produce unbiased survey estimates for fish distributed in shallow waters and near the surface, which is very important for many fish stock assessments and managements. Furthermore, it can also be used as a tool to observe the predation by seabirds on fish schools without interfering with their natural interspecific behavior, which traditionally has been very difficult. The use of the Kayak Drone is not restricted to these tasks, and we foresee that the Kayak Drone can be utilized in many different experiments where a silent platform is needed.
Plasma tumor necrosis factor-α is associated with sarcopenia in elderly individuals residing in agricultural and pastoral areas of Xinjiang, China
Authors: Wumaer Aishanjiang , Maimaitiwusiman Zhuoya , Xiao Wenwen , Xuekelati Saiyare , Liu Jinling , Musha Tajiguli , Wang Hongmei
Published: September 2022

Background

Inflammatory reactions play a significant role in the occurrence and development of sarcopenia. Determining the association between specific cytokines and sarcopenia may reveal the disease’s pathophysiological mechanism(s). Accordingly, the present study aimed to investigate the association between sarcopenia and inflammatory cytokines among the elderly natural population in agricultural and pastoral areas of Xinjiang.

Methods

We conducted a cross-sectional epidemiological survey of the community-dwelling older people using a multi-stage random sampling method in Mulei County in northern Xinjiang and Luopu County in southern Xinjiang from September 2017 to May 2018. Of the 2,100 participants, the statistical analyses included 1,838 participants with complete data. Comparisons of living habits, disease status, biochemical indexes, and levels of interleukin (IL)-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in sarcopenia and non-sarcopenia participants were made in this study.

Results

Our study revealed no significant differences (i.e., P > 0.05) in sex, age, ethnicity, smoking and drinking habits, serum renal function, total cholesterol, and diabetes in the elderly between the sarcopenia and non-sarcopenia groups in Xinjiang. However, triglyceride levels (P = 0.004), hypertension (P = 0.019), and abdominal obesity (P < 0.001) in the sarcopenia group were significantly higher than those in the non-sarcopenia group. Moreover, the levels of IL-10 (P < 0.001), IL-4 (P < 0.001), and TNF-α (P < 0.001) in the sarcopenia group were higher than those in the non-sarcopenia group after adjusting for sex, age, hypertension, blood lipid concentration, and obesity. Furthermore, after adjusting for sex, age, hypertension, obesity, and IL-10, IL-4, and IL-6 levels, an increased TNF-α level was also significantly associated with sarcopenia.

Conclusion

The results of the present study suggest that an increased plasma level of TNF-α is significantly associated with sarcopenia among elderly individuals residing in Xinjiang’s agricultural and pastoral areas. Further study is still needed to determine the physiological role of “immune aging” in the pathogenesis of sarcopenia.
Impact of incentives on COVID-19 vaccination; A systematic review
Authors: Mardi Parham , Djalalinia Shirin , Kargar Reza , Jamee Mahnaz , Esmaeili Abdar Zahra , Qorbani Mostafa
Published: September 2022

Introduction

Although vaccination is the most effective way to limit and overcome the COVID-19 pandemic, a considerable fraction of them are not intended to get vaccinated. This study aims to investigate the existing research evidence and evaluate the effectiveness and consequences of all incentives provided for increasing the uptake of COVID-19 vaccination.

Methods

A systematic search in PubMed, Web of Science (WoS), and SCOPUS from 2020 until October 10, 2021, was conducted on experimental studies evaluating the effects of incentives including cash, lottery voucher, and persuasive messages on COVID-19 vaccination intention and uptake. The study selection process, data extraction, and quality assessment were conducted independently by two investigators using Consolidated Standards of Reporting Trials (CONSORT 2010) checklist.

Results

Twenty-four records were included in the qualitative analysis. Most of the included studies assessed the effect of financial incentives. In 14 studies (58%) the assessed outcome was vaccination uptake and in nine (37.5%) others it was vaccination intention. One study considered self-reported vaccination status as the outcome. This study shows that high financial incentives and the Vax-a-million lottery are attributed to a higher vaccination rate, while the low amount of financial incentives, other lotteries, and persuasive messages have small or non-significant effects.

Conclusion

Paying a considerable amount of cash and Vax-a-million lottery are attributed to a higher vaccination. Nevertheless, there is a controversy over the effect of other incentives including other lotteries, low amount of cash, and messages on vaccination. It is noteworthy that, inconsistency and imprecision of included studies should be considered.
Aggressive intravenous hydration protocol of Lactated Ringer’s solution benefits patients with mild acute pancreatitis: A meta-analysis of 5 randomized controlled trials
Authors: Wu Fei , She Dong , Ao Qin , Zhang Shan , Li Jin
Published: September 2022

Objective

The aim of this meta-analysis was to determine the role of an aggressive intravenous hydration protocol of Lactated Ringer’s solution in patients with mild acute pancreatitis (MAP).

Methods

A systematic search was conducted in PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI) to identify randomized controlled trials (RCTs) published before August 19, 2022. The clinical outcomes were evaluated using the standard mean difference (SMD), mean difference (MD), risk ratio (RR), and 95% confidence interval (CI). The primary outcome was clinical improvement, while the secondary outcomes were the development of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), relief of epigastric abdominal pain, and length of hospital stay (LoH). Statistical analysis was performed with RevMan 5.4. Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) Working Group system was used to determine the quality of evidences.

Results

There were five RCTs with 370 MAP patients included, and the overall methodological quality was moderate. Aggressive hydration protocol was comparable to standard hydration protocol in terms of clinical improvement (RR = 1.33, 95%CI = 0.95–1.87, P = 0.10; very low evidence). Fewer events of SIRS (RR = 0.48, 95%CI = 0.31–0.72, P < 0.001; low evidence) and MODS (RR = 0.34, 95%CI = 0.13–0.91, P = 0.03; moderate evidence) were reported in patients receiving aggressive hydration protocol. Meanwhile, aggressive hydration protocol also significantly relieved epigastric abdominal pain (SMD = −0.53, 95%CI = −0.81 to −0.25, P < 0.001; low evidence) and shorten the LoH (MD = −2.36, 95%CI = −3.17 to −1.55, P < 0.001; low evidence) compared with standard hydration protocol.

Conclusion

For patients with MAP, aggressive hydration protocol may be more effective than standard hydration protocol at lowering SIRS and MODS rates, relieving epigastric abdominal pain, and shortening the LoH. Due to the small number of studies that are eligible and poor methodological quality of eligible studies, further studies are required to validate our findings.
Weaning from venous-arterial extracorporeal membrane oxygenation: The hemodynamic and clinical aspects of flow challenge test
Authors: Luo Jing-chao , Zhang Yi-jie , Hou Jun-yi , Luo Ming-hao , Liu Kai , Tu Guo-wei , Luo Zhe
Published: September 2022

The cardiac function reserve is crucial for the successful weaning of V-A ECMO. During the V-A ECMO weaning phase, the gradual reduction in pump flow converts the blood flow originally driven by the pump to native cardiac output and also transforms afterload (caused by retrograde flow) into ventricular preload, thus introducing a “flow challenge” to the native heart. In this perspective, we propose to use this flow challenge as a test to simulate the preload-to-afterload conversion to assess cardiac functional reserve quantitatively. With this short article we offer the hemodynamic and clinical aspects regarding the flow challenge test.
Unconventional genetic code systems in archaea
Authors: Meng Kexin , Chung Christina Z. , Söll Dieter , Krahn Natalie
Published: September 2022

Archaea constitute the third domain of life, distinct from bacteria and eukaryotes given their ability to tolerate extreme environments. To survive these harsh conditions, certain archaeal lineages possess unique genetic code systems to encode either selenocysteine or pyrrolysine, rare amino acids not found in all organisms. Furthermore, archaea utilize alternate tRNA-dependent pathways to biosynthesize and incorporate members of the 20 canonical amino acids. Recent discoveries of new archaeal species have revealed the co-occurrence of these genetic code systems within a single lineage. This review discusses the diverse genetic code systems of archaea, while detailing the associated biochemical elements and molecular mechanisms.
Discovery of Rickettsia spp. in mosquitoes collected in Georgia by metagenomics analysis and molecular characterization
Authors: Pollio Adam R. , Jiang Ju , Lee Sam S. , Gandhi Jaykumar S. , Knott Brian D. , Chunashvili Tamar , Conte Matthew A. , Walls Shannon D. , Hulseberg Christine E. , Farris Christina M. , Reinbold-Wasson Drew D. , Hang Jun
Published: September 2022

Arthropods have a broad and expanding worldwide presence and can transmit a variety of viral, bacterial, and parasite pathogens. A number of Rickettsia and Orientia species associated with ticks, fleas, lice, and mites have been detected in, or isolated from, patients with febrile illness and/or animal reservoirs throughout the world. Mosquitoes are not currently considered vectors for Rickettsia spp. pathogens to humans or to animals. In this study, we conducted a random metagenome next-generation sequencing (NGS) of 475 pools of Aedes, Culex, and Culiseta species of mosquitoes collected in Georgia from 2018 to 2019, identifying rickettsial gene sequences in 33 pools of mosquitoes. We further confirmed the findings of the Rickettsia by genus-specific quantitative PCR (qPCR) and multi-locus sequence typing (MLST). The NGS and MLST results indicate that Rickettsia spp. are closely related to Rickettsia bellii, which is not known to be pathogenic in humans. The results, together with other reports of Rickettsia spp. in mosquitoes and the susceptibility and transmissibility experiments, suggest that mosquitoes may play a role in the transmission cycle of Rickettsia spp.
Current treatment of chronic hepatitis B: Clinical aspects and future directions
Authors: Zhu Minmin , Wang Hui , Lou Tao , Xiong Pian , Zhang Jiebing , Li Lele , Sun Yuchao , Wu Yingping
Published: September 2022

Hepatitis B virus (HBV) infection is a public health threat worldwide, and there is no direct treatment yet available. In the event of infection, patients may present liver cirrhosis and cancer, which threaten the patients’ health globally, especially in the Asia-Pacific region and China. In 2019, Chinese hepatopathologists updated the 2015 Guidelines for the Prevention and Treatment of Chronic Hepatitis B as the clinical reference. The other versions formulated by the American Association for the Study of Liver Diseases (2018 AASLD guidelines) (AASLD, 2018), European Association for the Study of the Liver (2017 EASL guidelines) (EASL, 2017), and Asian-Pacific Association for the Study of the Liver (2015 APASL guidelines) (APASL, 2015) also provide clinical guidance. However, there are still some issues that need to be addressed. In the present study, the following aspects will be introduced successively: (1) Who should be treated in the general population according to the guidelines; (2) Treatment of specific populations infected with HBV; (3) Controversial issues in clinical practice; (4) Perspective.
Identification of region of difference and H37Rv-related deletion in Mycobacterium tuberculosis complex by structural variant detection and genome assembly
Authors: Liu Zhuochong , Jiang Zhonghua , Wu Wei , Xu Xinyi , Ma Yudong , Guo Xiaomei , Zhang Senlin , Sun Qun
Published: September 2022

Mycobacterium tuberculosis complex (MTBC), the main cause of TB in humans and animals, is an extreme example of genetic homogeneity, whereas it is still nevertheless separated into various lineages by numerous typing methods, which differ in phenotype, virulence, geographic distribution, and host preference. The large sequence polymorphism (LSP), incorporating region of difference (RD) and H37Rv-related deletion (RvD), is considered to be a powerful means of constructing phylogenetic relationships within MTBC. Although there have been many studies on LSP already, focusing on the distribution of RDs in MTBC and their impact on MTB phenotypes, a crumb of new lineages or sub-lineages have been excluded and RvDs have received less attention. We, therefore, sampled a dataset of 1,495 strains, containing 113 lineages from the laboratory collection, to screen for RDs and RvDs by structural variant detection and genome assembly, and examined the distribution of RvDs in MTBC, including RvD2, RvD5, and cobF region. Consistent with genealogical delineation by single nucleotide polymorphism (SNP), we identified 125 RDs and 5 RvDs at the species, lineage, or sub-lineage levels. The specificities of RDs and RvDs were further investigated in the remaining 10,218 strains, suggesting that most of them were highly specific to distinct phylogenetic groups, could be used as stable genetic markers in genotyping. More importantly, we identified 34 new lineage or evolutionary branch specific RDs and 2 RvDs, also demonstrated the distribution of known RDs and RvDs in MTBC. This study provides novel details about deletion events that have occurred in distinct phylogenetic groups and may help to understand the genealogical differentiation.
Long-term humoral immunogenicity, safety and protective efficacy of inactivated vaccine against reindeer rabies
Authors: Matveeva Irina , Karpova Olga , Nikitin Nikolai , Akilin Oleg , Yelnikov Vasiliy , Litenkova Irina , Melnik Roman , Melnik Nikolai , Asimov Karim , Zaberezhny Aleksey , Fyodorov Yriy , Markova Evgeniya
Published: September 2022

The core element of the reindeer rabies eradication strategy is regular application of vaccines to obtain and uphold a vaccination coverage sufficient for the ceasing of rabies virus transmission. This article presents the results of reindeer humoral immunity intensity and duration study after the immunization with two form of inactivated rabies vaccines (adjuvanted liquid vaccine and non-adjuvanted lyophilized vaccine) based on the Shchelkovo-51 rabies virus strain. Efficiency of post-vaccine immunity was assessed by measuring the animal blood serum virus-neutralizing antibody level in a neutralization test. The study determined the efficient rabies vaccine injection dose as equal to 3 ml. A single dose of 3 ml of these vaccines induced stable production of specific neutralizing antibodies in reindeer as early as 7 day after administration, and by 30 days after immunization, it significantly exceeded the minimal threshold level accepted by OIE. Two doses of vaccines administration with an interval of 30 days are required to achieve a strong immunity with the rabies-specific virus-neutralizing antibody titer of more than 0.5 IU/ml for at least 2 years. Our data do not support the benefit of an adjuvanted vaccine for the prevention of rabies in reindeer.
Microbial community composition in the rhizosphere of Pteris vittata and its effects on arsenic phytoremediation under a natural arsenic contamination gradient
Authors: Jia Pu , Li Fenglin , Zhang Shengchang , Wu Guanxiong , Wang Yutao , Li Jin-tian
Published: September 2022

Arsenic contamination causes numerous health problems for humans and wildlife via bioaccumulation in the food chain. Phytoremediation of arsenic-contaminated soils with the model arsenic hyperaccumulatorPteris vittataprovides a promising way to reduce the risk, in which the growth and arsenic absorption ability of plants and the biotransformation of soil arsenic may be greatly affected by rhizosphere microorganisms. However, the microbial community composition in the rhizosphere ofP. vittataand its functional role in arsenic phytoremediation are still poorly understood. To bridge this knowledge gap, we carried out a field investigation and pot experiment to explore the composition and functional implications of microbial communities in the rhizosphere of fourP.vittatapopulations with a natural arsenic contamination gradient. Arsenic pollution significantly reduced bacterial and fungal diversity in the rhizosphere ofP.vittata(p < 0.05) and played an important role in shaping the microbial community structure. The suitability of soil microbes for the growth ofP.vittatagradually decreased following increased soil arsenic levels, as indicated by the increased abundance of pathogenic fungi and parasitic bacteria and the decrease in symbiotic fungi. The analysis of arsenic-related functional gene abundance with AsChip revealed the gradual enrichment of the microbial genes involved in As(III) oxidation, As(V) reduction, and arsenic methylation and demethylation in the rhizosphere ofP.vittatafollowing increased arsenic levels (p < 0.05). The regulation of indigenous soil microbes through the field application of fungicide, but not bactericide, significantly reduced the remediation efficiency ofP.vittatagrown under an arsenic contamination gradient, indicating the important role of indigenous fungal groups in the remediation of arsenic-contaminated soil. This study has important implications for the functional role and application prospects of soil microorganisms in the phytoremediation of arsenic-polluted soil.
Identification of hexosamine biosynthesis pathway as a novel prognostic signature and its correlation with immune infiltration in bladder cancer
Authors: Cui Yangyan , Feng Hanyi , Liu Jiakuan , Wu Jiajun , Zhu Rujian , Huang Ruimin , Yan Jun
Published: September 2022

Background: Urinary bladder cancer (UBC) is one of the common urological malignancies, lacking reliable biomarkers to predict clinical outcomes in UBC patients. Thus, it is needed to identify the novel diagnostic/prognostic biomarkers to stratify the high-risk UBC patients. As a shunt pathway of glycolysis, the hexosamine biosynthesis pathway (HBP) has been implicated in carcinogenesis. However, its prognostic value in UBC remains unclear.

Methods: The RNA sequencing and mRNA microarray datasets were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus databases. The expression levels of five HBP genes were analyzed in normal and UBC samples, and their associations with stage, grade and survival were plotted. The performance of HBP risk group was evaluated by receiver-operating characteristics (ROC) curve. The HBP signature was generated by Gene Set Variation Analysis (GSVA) and its association with clinicopathological parameters and survival were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to examine the potential biological functions of HBP using DAVID online tool. The infiltration estimation fraction of immune cells was performed using CIBERSORT-ABS algorithm. Gene set enrichment analysis (GSEA) was used to explore the potential function of HBP in tumor immunoregulation.

Results: Four HBP genes were upregulated in UBCs compared to normal tissues in TCGA-BLCA dataset. The upregulation of all five HBP genes was significantly associated with tumor grade and stage of UBC in three independent UBC datasets. The expression of HBP genes predicted poor clinical outcomes in UBC patients in both TCGA-BLCA and GSE13507 datasets. The high-risk group based on HBP genes showed a poor prognosis. Furthermore, HBP signature was positively associated with tumor grade and stage in TCGA-BLCA dataset and with tumor grade, stage, distal metastasis and poor survival in GSE13507 dataset. Interestingly, high-HBP signature group exhibited a high infiltration of immune cells, particularly the macrophage population.

Conclusion: We identified that HBP was a promising prognostic biomarker in UBC patients and strongly associated with immune infiltration.
Respiratory syncytial virus infection changes the piwi-interacting RNA content of airway epithelial cells
Authors: Corsello Tiziana , Kudlicki Andrzej S , Liu Tianshuang , Casola Antonella
Published: September 2022

Piwi-interacting RNAs (piRNAs) are small non-coding RNAs (sncRNAs) of about 26–32 nucleotides in length and represent the largest class of sncRNA molecules expressed in animal cells. piRNAs have been shown to play a crucial role to safeguard the genome, maintaining genome complexity and integrity, as they suppress the insertional mutations caused by transposable elements. However, there is growing evidence for the role of piRNAs in controlling gene expression in somatic cells as well. Little is known about changes in piRNA expression and possible function occurring in response to viral infections. In this study, we investigated the piRNA expression profile, using a human piRNA microarray, in human small airway epithelial (SAE) cells infected with respiratory syncytial virus (RSV), a leading cause of acute respiratory tract infections in children. We found a time-dependent increase in piRNAs differentially expressed in RSV-infected SAE cells. We validated the top piRNAs upregulated and downregulated at 24 h post-infection by RT-qPCR and identified potential targets. We then used Gene Ontology (GO) tool to predict the biological processes of the predicted targets of the most represented piRNAs in infected cells over the time course of RSV infection. We found that the most significant groups of targets of regulated piRNAs are related to cytoskeletal or Golgi organization and nucleic acid/nucleotide binding at 15 and 24 h p.i. To identify common patterns of time-dependent responses to infection, we clustered the significantly regulated expression profiles. Each of the clusters of temporal profiles have a distinct set of potential targets of the piRNAs in the cluster Understanding changes in piRNA expression in RSV-infected airway epithelial cells will increase our knowledge of the piRNA role in viral infection and might identify novel therapeutic targets for viral lung-mediated diseases.
Delineating specific regions of N- terminal domain of T3SS ATPase YsaN of Yersinia enterocolitica governing its different oligomerization states
Authors: Kumar Rajeev , Roy Chittran , Datta Saumen
Published: September 2022

Oligomerization of YsaN, a putative T3SS-ATPase is a necessary and crucial event for T3SS functioning in Y. enterocolitica. Different oligomeric states have been proposed for similar ATPases, yet, the true nature of its activation and formation of different oligomers is still poorly understood. In-vitro studies of YsaN reveal that its activation and oligomerization depend on its N-terminal region and occur as a result of active catalysis of ATP in an ATP concentration-dependent manner following two-step cooperative kinetics. Also, the N-terminal 83 amino acid residues of YsaN are crucial for higher-order oligomer formation while YsaN∆83 is capable of hexamer formation upon oligomerization. Enzyme kinetics study shows reduced ATPase activity of YsaN∆83 (3.19 ± 0.09 μmol/min/mg) in comparison to YsaN (9.076 ± 0.72 μmol/min/mg). Negative-TEM study of YsaN and YsaN∆83 oligomer suggests that the formation of higher-order oligomer (probably dodecamer) occurs by stacking of two hexamers through their N-terminal faces involving N-terminal 83 amino acid residues which have been further supported by the docking of two hexamers during the in-silico study. These results suggest that YsaN is an oligomerization-activated T3SS ATPase, where distinct regions of its N-terminal domain regulate its different oligomeric nature and is essential for its activation.
Walking parameters of older adults from a lower back inertial measurement unit, a 6-year longitudinal observational study
Authors: Elshehabi Morad , Del Din Silvia , Hobert Markus A. , Warmerdam Elke , Sünkel Ulrike , Schmitz-Hübsch Tanja , Behncke Lisa Marie , Heinzel Sebastian , Brockmann Kathrin , Metzger Florian G. , Schlenstedt Christian , Rochester Lynn , Hansen Clint , Berg Daniela , Maetzler Walter
Published: September 2022

Gait changes during aging and differs between sexes. Inertial measurement units (IMUs) enable accurate quantitative evaluations of gait in ambulatory environments and in large populations. This study aims to provide IMU-based gait parameters’ values derived from a large longitudinal cohort study in older adults. We measured gait parameters, such as velocity, step length, time, variability, and asymmetry, from straight, self-paced 20-m walks in older adults (four visits: 715/1102/1017/957 participants) every second year over 6 years using an IMU at the lower back. Moreover, we calculated the associations of gait parameters with sex and age. Women showed lower gait speed, step length, step time, stride time, swing time, and stance time, compared to men. Longitudinal analyses suggest that these parameters are at least partly deteriorating within the assessment period of 2 years, especially in men and at an older age. Variability and asymmetry parameters show a less clear sex- and age-associated pattern. Altogether, our large longitudinal dataset provides the first sex-specific information on which parameters are particularly promising for the detection of age-related gait changes that can be extracted from an IMU on the lower back. This information may be helpful for future observational and treatment studies investigating sex and age-related effects on gait, as well as for studies investigating age-related diseases.
Case report: Identification and clinical phenotypic analysis of novel mutation of the PPP1CB gene in NSLH2 syndrome
Authors: He Xuemei , Ma Xiuli , Wang Jing , Zou Zhuo , Huang Haoyu , Ren Jian , Liu Chunming , Zheng Nan , Ma Jing , Liu Yun
Published: September 2022

Objective

To screen and analyze the genetic mutations in the PPP1CB gene in a patient with Noonan syndrome with loose anagen hair-2 (NSLH2) in Yunnan Province, China and explore the possible molecular pathogenesis.

Methods

After obtaining informed consent, we collected the patient's medical history and carried out physical and laboratory examinations for the NSLH2 proband and the family members. Genomic DNA was extracted from the peripheral blood of all individuals. The coding regions including all pathogenic exons, parts of introns, and promoters of genes were sequenced by next-generation sequencing. Pathogenic mutations, which were detected in the probands and their parents, were verified by Sanger sequencing.

Results

The clinical manifestations of NSLH2 included prominent forehead, yellowish hair, slightly wide eye distance, sparse eyebrows, bilateral auricle deformity, reduced muscle tension, and cardiac and visual abnormalities. The proband carried a c.371A>G mutation in exon 3 of PPP1CB, which is a missense mutation. This was a de novo mutation as the parents of the proband showed no mutation at this site.

Conclusion

In this study, we identified a novel mutation of PPP1CB, which enriched the mutation spectrum of the PPP1CB gene and provided a basis for the diagnosis of NSLH2.
Representation of prefrontal axonal efferents in the thalamic nucleus reuniens in a rodent model of fetal alcohol exposure during third trimester
Authors: Smith Ian F. , Gursky Zachary H. , Klintsova Anna Y.
Published: September 2022

Alcohol exposure (AE) during the prenatal period could result in fetal alcohol spectrum disorders (FASDs), one of many deficits of which is impaired executive functioning (EF). EF relies on the coordination of activity between the medial prefrontal cortex (mPFC) and hippocampus (HPC) by the thalamic nucleus reuniens (Re), a structure that has been shown to be damaged following high-dose AE in a rodent model of third trimester exposure. Notably, mPFC neurons do not project directly to HPC, but rather communicate with it via a disynaptic pathway where the first cortical axons synapse on neurons in Re, which in turn send axons to make contacts with hippocampal cells. This experiment investigated the effect of binge AE (5.25 g/kg/day, two doses 2 h apart) during postnatal days 4–9 on the length of medial prefrontal axonal projections within Re in Long Evans rat. AE reduced the cumulative length of mPFC-originating axon terminals in Re in female rats, with male rats exhibiting shorter cumulative lengths when compared to female procedural control animals. Additionally, Re volume was decreased in AE animals, a finding that reproduced previously reported data. This experiment helps us better understand how early life AE affects prefrontal-thalamic-hippocampal connectivity that could underlie subsequent EF deficits.
Mapping the research trends of astrocytes in stroke: A bibliometric analysis
Authors: Ding Zhibin , Jiang Nan , Yang Ting , Han Hongxia , Hou Miaomiao , Kumar Gajendra , Wu Yige , Song Lijuan , Li Xinyi , Ma Cungen , Su Yanbing
Published: September 2022

Background

Stroke, including ischemic stroke and hemorrhagic stroke, possesses complex pathological mechanisms such as neuroinflammation, oxidative stress and blood-brain barrier damage. Astrocyte functions have been reported during injury, neuroprotection and cell crosstalk. It plays a key role in exacerbating stroke injury, promoting neurological repair and enhancing neuroregeneration.

Aim

This holistic bibliometric analysis aimed to provide a general overview of the recent advancement and the hotspots in the field of stroke and astrocyte from 2001 to 2021.

Materials and methods

Publications between 2001 and 2021, related to stroke and astrocyte were retrieved from the Web of Science (WOS) and analyzed in Gephi and VOSviewer.

Results

In total, 3789 documents were extracted from the WOS databases. The publications showed stable growth since 2001. The United States and China were the most prolific countries and University of California San Francisco and Oakland University were the most influential institutes. The top four most productive journals were Brain Research, Journal of Cerebral Blood Flow and Metabolism, Glia and Journal of Neuroinflammation. Keywords frequency and co-occurrence analysis revealed that the topics related to “micro-RNA”, “toll like receptor”, “neuroinflammation”, “autophagy” and “interleukin” were research frontiers. The field of stroke and astrocyte focused on several aspects, such as the role of astrocytes in the treatment of stroke, metabolic changes in astrocytes, the protective role of apoptosis in astrocytes after oxidative stress injury and neurovascular units.

Conclusion

This comprehensive bibliometric study provides an updated perspective on the trend of research associated with stroke and astrocyte. It will benefit scientific community to identify the important issues, future directions and provide a novel understanding of stroke pathophysiology, hotspots and frontiers to facilitate future research direction.
A genetically identified population of layer 4 neurons in auditory cortex that contributes to pre-pulse inhibition of the acoustic startle response
Authors: Weible Aldis P. , Yavorska Iryna , Narayanan Arthy , Wehr Michael
Published: September 2022

A fundamental task faced by the auditory system is the detection of events that are signaled by fluctuations in sound. Spiking in auditory cortical neurons is critical for sound detection, but the causal roles of specific cell types and circuits are still mostly unknown. Here we tested the role of a genetically identified population of layer 4 auditory cortical neurons in sound detection. We measured sound detection using a common variant of pre-pulse inhibition of the acoustic startle response, in which a silent gap in background noise acts as a cue that attenuates startle. We used a Gpr26-Cre driver line, which we found expressed predominantly in layer 4 of auditory cortex. Photostimulation of these cells, which were responsive to gaps in noise, was sufficient to attenuate the startle reflex. Photosuppression of these cells reduced neural responses to gaps throughout cortex, and impaired behavioral gap detection. These data demonstrate that cortical Gpr26 neurons are both necessary and sufficient for top–down modulation of the acoustic startle reflex, and are thus likely to be involved in sound detection.
A novel nomogram to predict hemorrhagic transformation in ischemic stroke patients after intravenous thrombolysis
Authors: Yang Miaomiao , Zhong Wei , Zou Wenhui , Peng Jingzi , Tang Xiangqi
Published: September 2022

Background

Hemorrhagic transformation (HT) is the most serious complication of ischemic stroke patients after intravenous thrombolysis and leads to a poor clinical prognosis. This study aimed to determine the independent predictors associated with HT in stroke patients with intravenous thrombolysis and to establish and validate a nomogram that combines with predictors to predict the probability of HT after intravenous thrombolysis in patients with ischemic stroke.

Method

This study enrolled ischemic stroke patients with intravenous thrombolysis from December 2016 to June 2022. All the patients were divided into training and validation cohorts. The nomogram was composed of the significant predictors for HT in the training cohort as obtained by the multivariate logistic regression analysis. The area under the receiver operating characteristic curve was used to assess the discriminative performance of the nomogram. The calibration performance of the nomogram was assessed by the Hosmer–Lemeshow goodness-of-fit test and calibration plots. Decision curve analysis was used to test the clinical validity of the nomogram.

Results

A total of 394 patients with intravenous thrombolysis were enrolled in the study. In the training cohort (n = 257), 45 patients had HT after intravenous thrombolysis. Multivariate logistic regression analysis demonstrated early infarct signs (OR, 7.954; 95% CI, 3.553-17.803; P < 0.001), NIHSS scores (OR, 1.110; 95% CI, 1.054-1.168; P < 0.001), uric acid (OR, 0.993; 95% CI, 0.989–0.997; P = 0.001), and albumin-to-globulin ratio (OR, 0.109; 95% CI, 0.023–0.508; P = 0.005) were independent predictors for HT and constructed the nomogram. In the training and validation cohorts, the AUC of the nomogram was 0.859 and 0.839, respectively. The Hosmer–Lemeshow goodness-of-fit test and calibration plot showed good concordance between predicted and observed probability in the training and validation cohorts. Decision curve analysis indicated that the nomogram was significantly useful for predicting HT in the training and further confirmed in the validation cohort.

Conclusion

This study proposes a novel and practical nomogram based on early infarct signs, NIHSS scores, uric acid, and albumin-to-globulin ratio that can well predict the probability of HT after intravenous thrombolysis in patients with ischemic stroke.
Indexes for motor performance assessment in job integration/reintegration of people with neuromuscular disorders: A systematic review
Authors: Chini Giorgia , Fiori Lorenzo , Tatarelli Antonella , Varrecchia Tiwana , Draicchio Francesco , Ranavolo Alberto
Published: September 2022

Individuals of working age affected by neuromuscular disorders frequently experience issues with their capacity to get employment, difficulty at work, and premature work interruption. Anyway, individuals with a disability could be able to return to work, thanks to targeted rehabilitation as well as ergonomic and training interventions. Biomechanical and physiological indexes are important for evaluating motor and muscle performance and determining the success of job integration initiatives. Therefore, it is necessary to determinate which indexes from the literature are the most appropriate to evaluate the effectiveness and efficiency of the return-to-work programs. To identify current and future valuable indexes, this study uses a systematic literature review methodology for selecting articles published from 2011 to March 30, 2021 from Scopus, Web of Science, and PubMed and for checking the eligibility and the potential bias risks. The most used indexes for motor performance assessment were identified, categorized, and analyzed. This review revealed a great potential for kinetic, kinematic, surface electromyography, postural, and other biomechanical and physiological indexes to be used for job integration/reintegration. Indeed, wearable miniaturized sensors, kinematic, kinetic, and sEMG-based indexes can be used to control collaborative robots, classify residual motor functions, and assess pre–post-rehabilitation and ergonomic therapies.