bluuebunny/crossref_metadata_2025 huggingface dataset:
Trace Metal Residues in Swimming Warrior Crab Callinectes bellicosus: A Consumption Risk
Authors: Castro-Elenes Marisol , Rodríguez-Meza G. Durga , Pérez-González Ernestina , González-Ocampo Héctor A.
Published: December 2021

This study was carried out in the Navachiste coastal lagoon, Mexico, surrounded by intensive agricultural and aquaculture activities that cause environmental pollution by the deposition of trace metal residues in the sediments of this coastal lagoon. The trace metals are bioaccumulated by benthic organisms such as the blue swimming warrior crab, Callinectes bellicosus, which inhabits this lagoon and is consumed by humans. Ninety-five C. bellicosus edible tissue samples were collected (April 2014–January 2015). The extraction procedure of the trace metals in edible tissue samples was carried out by acid digestion with nitric acid. Based on the Environmental Protection Agency (EPA) of the United States, two indices were used to measure health risk: the estimated daily intake (EDI) and the target hazard quotient (THQ). The hazard index (HI) was used to calculate the probability of adverse carcinogenic risk and the target hazard quotient per sample (MHI) to calculate the probability of developing a carcinogenic or non-carcinogenic risk. The analysis of variance (ANOVA) showed significant differences among trace metal concentrations (p < 0.01), but all trace metal concentrations in the edible tissues of C. bellicosus were higher than the maximum residual limits (MRLs). The highest EDI was for Zn, Fe, and Cu, showing that the consumption of these crabs might represent health risks. The THQ >1 was for Ni, Zn, Cd, and Cu, and the HI = 16 revealed the risk of C. bellicosus for high-level consumers. The MHI showed that 98% of samples presented a THQ >1, implying a high rate of bioaccumulation of trace metals by the crabs independent of the sampling site in the NAV. The presence of trace metals in the edible tissue of crabs reflects contamination by trace metals, and the indices results mean that the NAV lagoon is constantly polluted with trace metal residues by neighboring agriculture and aquaculture activities. These trace metal residues are being bioaccumulated in the edible tissues of C. bellicosus due to its feeding habits, resulting in a health risk if its consumption is high, including carcinogenic and non-carcinogenic risks.
On the Nature of Organs and Organ Systems – A Chapter in the History and Philosophy of Biology
Authors: Minelli Alessandro
Published: December 2021

Contrasting definitions of organs based either on function or on strictly morphological criteria are the legacy of a tradition starting with Aristotle. This floating characterization of organs in terms of both form and function extends also to organ systems. The first section of this review outlines the notions of organ and body part as defined, explicitly or implicitly, in representative works of nineteenth century’s comparative morphology. The lack of a clear distinction between the two notions led to problems in Owen’s approach to the comparative method (definition of homolog vs. nature of the vertebrate archetype) and to a paradoxical formulation, by Anton Dohrn, of the principle of functional change. Starting from the second half of the twentieth century, with the extensive use of morphological data in phylogenetic analyses, both terms – organ and body part – have been often set aside, to leave room for a comparison between variously characterized attributes (character states) of the taxa to be compared. Throughout the last two centuries, there have been also efforts to characterize organs or body parts in terms of the underlying developmental dynamics, both in the context of classical descriptive embryology and according to models suggested by developmental genetics. Functionally defined organ are occasionally co-extensive with morphologically defined body parts, nevertheless a clear distinction between the former and the latter is a necessary prerequisite to a study of their evolution: this issue is discussed here on the example of the evolution of hermaphroditism and gonad structure and function.
COVID-19 Restrictions in a Nature Reserve Reveal the Costs of Human Presence for the Threatened Nubian Ibex (Capra nubiana)
Authors: Zukerman Yuval , Sigal Zehava , Berger-Tal Oded
Published: December 2021

The increasing pressure of ecotourism on wildlife in their natural habitats leads many wild animals to alter their behaviors. The restrictions issued in many places due to COVID-19 provide a rare opportunity to examine wildlife behavior in nature reserves with reduced human presence, and to reveal the impact of human visitation on the behaviors and fitness of local wildlife species. In 2019 and 2020 we placed trail cameras next to two natural springs in the Israeli Negev Desert, Ein-Avdat and Ein-Shaviv, located 9 km apart. Both sites serve as the main water source for local Nubian ibex (Capra nubiana) populations, but Ein-Avdat is situated within a popular national park into which visitors’ entrance was restricted due to COVID-19 regulations in 2020, while Ein-Shaviv is more remote and thus attracts only few visitors regardless of COVID-19 regulations. Our study revealed that during 2020, ibex in Ein-Avdat arrived to drink earlier in the day and the population’s Female:Kids ratio more than doubled. These changes were not observed in Ein-Shaviv. We found that the daily number of visitors in Ein-Avdat affected the arrival time of ibex to the water pool. We conclude that the reduced number of visitors to Ein-Avdat in 2020 compared to 2019 may have allowed ibex to arrive in preferred hours, and may have contributed to the increased kid-to-females ratio. Our study shows that behavioral adaptions to human visitation in nature reserves might carry a high fitness cost.
Identification of Hub Genes Associated With Tuberculous Pleurisy by Integrated Bioinformatics Analysis
Authors: Shi Lei , Wen Zilu , Li Hongwei , Song Yanzheng
Published: December 2021

Improving the understanding of the molecular mechanism of tuberculous pleurisy is required to develop diagnosis and new therapy strategies of targeted genes. The purpose of this study is to identify important genes related to tuberculous pleurisy. In this study, the expression profile obtained by sequencing the surgically resected pleural tissue was used to explore the differentially co-expressed genes between tuberculous pleurisy tissue and normal tissue. 29 differentially co-expressed genes were screened by weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis methods. According to the functional annotation analysis of R clusterProfiler software package, these genes are mainly enriched in nucleotide−sugar biosynthetic process (biological process), ficolin−1−rich granule lumen (cell component), and electron transfer activity (molecular function). In addition, in the protein-protein interaction (PPI) network, 20 hub genes of DEGs and WCGNA genes were identified using the CytoHubba plug-in of Cytoscape. In the end, RPL17 was identified as a gene that can be the biomarker of tuberculous pleurisy. At the same time, there are seven genes that may have relationship with the disease (UBA7, NDUFB8, UQCRFS1, JUNB, PSMC4, PHPT1, and MAPK11).
Genetic Liability to Insomnia and Lung Cancer Risk: A Mendelian Randomization Analysis
Authors: Shen Jiayi , Zhou Huaqiang , Liu Jiaqing , Zhang Yaxiong , Zhou Ting , Chen Gang , Fang Wenfeng , Yang Yunpeng , Huang Yan , Zhang Li
Published: December 2021

Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer death worldwide, making its prevention an urgent issue. Meanwhile, the estimated prevalence of insomnia was as high as 30% globally. Research on the causal effect of insomnia on lung cancer incidence is still lacking. In this study, we aimed to assess the causality between the genetic liability to insomnia and lung cancer. We performed a two-sample Mendelian randomization analysis (inverse variance weighted) to determine the causality between the genetic liability to insomnia and lung cancer. Subgroup analysis was conducted, which included lung adenocarcinoma and lung squamous cell carcinoma. In the sensitivity analysis, we conducted heterogeneity test, MR Egger, single SNP analysis, leave-one-out analysis, and MR PRESSO. There were causalities between the genetic susceptibility to insomnia and increased incidence of lung cancer [odds ratio (95% confidence interval), 1.35 (1.14–1.59); P, < 0.001], lung adenocarcinoma [odds ratio (95% confidence interval), 1.35 (1.07–1.70); P, 0.01], and lung squamous cell carcinoma [odds ratio (95% confidence interval), 1.35 (1.06–1.72), P, 0.02]. No violation of Mendelian randomization assumptions was observed in the sensitivity analysis. There was a causal relationship between the genetic susceptibility to insomnia and the lung cancer, which was also observed in lung adenocarcinoma and lung squamous cell carcinoma. The underlying mechanism remains unknown. Effective intervention and management for insomnia were recommended to improve the sleep quality and to prevent lung cancer. Moreover, regular screening for lung cancer may be beneficial for patients with insomnia.
Molecular Diagnosis of Muscular Dystrophy Patients in Western Indian Population: A Comprehensive Mutation Analysis Using Amplicon Sequencing
Authors: Patel Komal M. , Bhatt Arpan D. , Shah Krati , Waghela Bhargav N. , Pandit Ramesh J. , Sheth Harsh , Joshi Chaitanya G. , Joshi Madhvi N.
Published: December 2021

Muscular Dystrophies (MDs) are a group of inherited diseases and heterogeneous in nature. To date, 40 different genes have been reported for the occurrence and/or progression of MDs. This study was conducted to demonstrate the application of next-generation sequencing (NGS) in developing a time-saving and cost-effective diagnostic method to detect single nucleotide variants (SNVs) and copy number variants (CNVs) in a single test. A total of 123 cases clinically suspected of MD were enrolled in this study. Amplicon panel-based diagnosis was carried out for 102 (DMD/BMD) cases and the results were further screened using multiplex ligation-dependent probe amplification (MLPA). Whilst in the case of LGMD (N = 19) and UMD (N = 2), only NGS panel-based analysis was carried out. We identified the large deletions in 74.50% (76/102) of the cases screened with query DMD or BMD. Further, the large deletion in CAPN3 gene (N = 3) and known SNV mutations (N = 4) were identified in LGMD patients. Together, the total diagnosis rate for this amplicon panel was 70.73% (87/123) which demonstrated the utility of panel-based diagnosis for high throughput, affordable, and time-saving diagnostic strategy. Collectively, present study demonstrates that the panel based NGS sequencing could be superior over to MLPA.
Identification of Immune-Related Biomarkers for Sciatica in Peripheral Blood
Authors: Jin Xin , Wang Jun , Ge Lina , Hu Qing
Published: December 2021

Objective: Sciatica pertains to neuropathic pain that has been associated with inflammatory response. We aimed to identify significant immune-related biomarkers for sciatica in peripheral blood.

Methods: We utilized the GSE150408 expression profiling data from the Gene Expression Omnibus (GEO) database as the training dataset and extracted immune-related genes for further analysis. Differentially expressed immune-related genes (DEIRGs) between healthy controls and patients with sciatica were selected using the “limma” package and verified in clinical specimens by quantitative reverse transcription PCR (RT-qPCR). A diagnostic immune-related gene signature was established using the training model and random forest (RF), generalized linear model (GLM), and support vector machine (SVM) models. Sciatica patient subtypes were identified using the consensus clustering method.

Results: Thirteen significant DEIRGs were acquired, of which five (CRP, EREG, FAM19A4, RLN1, and WFIKKN1) were selected to establish a diagnostic immune-related gene signature according to the most appropriate training model, namely, the RF model. A clinical application nomogram model was established based on the expression level of the five DEIRGs. The sciatica patients were divided into two subtypes (C1 and C2) according to the consensus clustering method.

Conclusions: Our research established a diagnostic five immune-related gene signature to discriminate sciatica and identified two sciatica subtypes, which may be beneficial to the clinical diagnosis and treatment of sciatica.
Deregulation of ncRNA in Neurodegenerative Disease: Focus on circRNA, lncRNA and miRNA in Amyotrophic Lateral Sclerosis
Authors: Ruffo Paola , Strafella Claudia , Cascella Raffaella , Caputo Valerio , Conforti Francesca Luisa , Andò Sebastiano , Giardina Emiliano
Published: December 2021

Parallel and massive sequencing of total RNA samples derived from different samples are possible thanks to the use of NGS (Next Generation Sequencing) technologies. This allowed characterizing the transcriptomic profile of both cell and tissue populations, increasing the knowledge of the molecular pathological processes of complex diseases, such as neurodegenerative diseases (NDs). Among the NDs, Amyotrophic Lateral Sclerosis (ALS) is caused by the progressive loss of motor neurons (MNs), and, to date, the diagnosis is often made by exclusion because there is no specific symptomatologic picture. For this reason, it is important to search for biomarkers that are clinically useful for carrying out a fast and accurate diagnosis of ALS. Thanks to various studies, it has been possible to propose several molecular mechanisms associated with the disease, some of which include the action of non-coding RNA, including circRNAs, miRNAs, and lncRNAs which will be discussed in the present review. The evidence analyzed in this review highlights the importance of conducting studies to better characterize the different ncRNAs in the disease to use them as possible diagnostic, prognostic, and/or predictive biomarkers of ALS and other NDs.
SNPs in miRNAs and Target Sequences: Role in Cancer and Diabetes
Authors: Chhichholiya Yogita , Suryan Aman Kumar , Suman Prabhat , Munshi Anjana , Singh Sandeep
Published: December 2021

miRNAs are fascinating molecular players for gene regulation as individual miRNA can control multiple targets and a single target can be regulated by multiple miRNAs. Loss of miRNA regulated gene expression is often reported to be implicated in various human diseases like diabetes and cancer. Recently, geneticists across the world started reporting single nucleotide polymorphism (SNPs) in seed sequences of miRNAs. Similarly, SNPs are also reported in various target sequences of these miRNAs. Both the scenarios lead to dysregulated gene expression which may result in the progression of diseases. In the present paper, we explore SNPs in various miRNAs and their target sequences reported in various human cancers as well as diabetes. Similarly, we also present evidence of these mutations in various other human diseases.
Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease
Authors: Wong Chun-Shu , Buckner Clarisa M. , Lage Silvia Lucena , Pei Luxin , Assis Felipe L. , Dahlstrom Eric W. , Anzick Sarah L. , Virtaneva Kimmo , Rupert Adam , Davis Jeremy L. , Zhou Ting , Laidlaw Elizabeth , Manion Maura , Galindo Frances , Anderson Megan , Seamon Catherine A. , Sneller Michael C. , Lisco Andrea , Deleage Claire , Pittaluga Stefania , Moir Susan , Sereti Irini
Published: December 2021

Low nadir CD4 T-cell counts in HIV+patients are associated with high morbidity and mortality and lasting immune dysfunction, even after antiretroviral therapy (ART). The early events of immune recovery of T cells and B cells in severely lymphopenic HIV+patients have not been fully characterized. In a cohort of lymphopenic (CD4 T-cell count < 100/µL) HIV+patients, we studied mononuclear cells isolated from peripheral blood (PB) and lymph nodes (LN) pre-ART (n = 40) and 6-8 weeks post-ART (n = 30) with evaluation of cellular immunophenotypes; histology on LN sections; functionality of circulating T follicular helper (cTfh) cells; transcriptional and B-cell receptor profile on unfractionated LN and PB samples; and plasma biomarker measurements. A group of 19 healthy controls (HC, n = 19) was used as a comparator. T-cell and B-cell lymphopenia was present in PB pre-ART in HIV+patients. CD4:CD8 and CD4 T- and B-cell PB subsets partly normalized compared to HC post-ART as viral load decreased. Strikingly in LN, ART led to a rapid decrease in interferon signaling pathways and an increase in Tfh, germinal center and IgD-CD27-B cells, consistent with histological findings of post-ART follicular hyperplasia. However, there was evidence of cTfh cells with decreased helper capacity and of limited B-cell receptor diversification post-ART. In conclusion, we found early signs of immune reconstitution, evidenced by a surge in LN germinal center cells, albeit limited in functionality, in HIV+patients who initiate ART late in disease.
Potential Efficacy of Chitosan-Poly (Lactide-Co-Glycolide)-Encapsulated Trivalent Immersion Vaccine in Olive Flounder (Paralichthys olivaceus) Against Viral Hemorrhagic Septicemia Virus, Streptococcus parauberis Serotype I, and Miamiensis avidus (Scuticociliate)
Authors: Kole Sajal , Dar Showkat Ahmad , Shin Su-Mi , Jeong Hyeon-Jong , Jung Sung-Ju
Published: December 2021

Olive flounder (Paralichthys olivaceus) is the most valuable aquaculture species in Korea, corresponding to ~60% of its total production. However, infectious diseases often break out among farmed flounders, causing high mortality and substantial economic losses. Although some deleterious pathogens, such as Vibrio spp. and Streptococcus iniae, have been eradicated or contained over the years through vaccination and proper health management, the current disease status of Korean flounder shows that the viral hemorrhagic septicemia virus (VHSV), Streptococcus parauberis, and Miamiensis avidus are causing serious disease problem in recent years. Furthermore, these three pathogens have differing optimal temperature and can attack young fingerlings and mature fish throughout the year-round culture cycle. In this context, we developed a chitosan-poly(lactide-co-glycolide) (PLGA)-encapsulated trivalent vaccine containing formalin-killed VHSV, S. parauberis serotype-I, and M. avidus and administered it to olive flounder fingerlings by immersion route using a prime-boost strategy. At 35 days post-initial vaccination, three separate challenge experiments were conducted via intraperitoneal injection with the three targeted pathogens at their respective optimal temperature. The relative percentages of survival were 66.63%, 53.3%, and 66.75% in the group immunized against VHSV, S. parauberis serotype-I, and M. avidus, respectively, compared to the non-vaccinated challenge (NVC) control group. The immunized fish also demonstrated significantly (p < 0.05) higher specific antibody titers in serum and higher transcript levels of Ig genes in the mucosal and systemic tissues than those of NVC control fish. Furthermore, the study showed significant (p < 0.05) upregulation of various immune genes in the vaccinated fish, suggesting induction of strong protective immune response, ultimately leading to improved survival against the three pathogens. Thus, the formulated mucosal vaccine can be an effective prophylactic measure against VHS, streptococcosis, and scuticociliatosis diseases in olive flounder.
Low-Salt Diet Attenuates B-Cell- and Myeloid-Cell-Driven Experimental Arthritides by Affecting Innate as Well as Adaptive Immune Mechanisms
Authors: Sehnert Bettina , Pohle Sandy , Heuberger Cornelia , Rzepka Rita , Seidl Maximilian , Nimmerjahn Falk , Chevalier Nina , Titze Jens , Voll Reinhard E.
Published: December 2021

A link between high sodium chloride (salt) intake and the development of autoimmune diseases was previously reported. These earlier studies demonstrated exacerbation of experimental autoimmune encephalomyelitis and colitis by excess salt intake associated with Th17- and macrophage-mediated mechanisms. Little is known about the impact of dietary salt intake on experimental arthritides. Here, we investigated if salt restriction can exert beneficial effects on collagen-induced arthritis (CIA) and K/BxN serum transfer-induced arthritis (STIA). CIA depends on both adaptive and innate immunity, while STIA predominantly mimics the innate immune cell-driven effector phase of arthritis. In both models, low salt (LS) diet significantly decreased arthritis severity compared to regular salt (RS) and high salt (HS) diet. We did not observe an aggravation of arthritis with HS diet compared to RS diet. Remarkably, in STIA, LS diet was as effective as IL-1 receptor blocking treatment. Complement-fixing anti-CII IgG2a antibodies are associated with inflammatory cell infiltration and cartilage destruction. LS diet reduced anti-CII IgG2a levels in CIA and decreased the anti-CII IgG2a/IgG1 ratios pointing toward a more Th2-like response. Significantly less inflammatory joint infiltrates and cartilage breakdown associated with reduced protein concentrations of IL-1 beta (CIA and STIA), IL-17 (CIA), and the monocyte chemoattractant protein-1 (MCP-1) (CIA) were detected in mice receiving LS diet compared to HS diet. However, we did not find a reduced IL-17A expression in CD4+T cells upon salt restriction in CIA. Analysis of mRNA transcripts and immunoblots revealed a link between LS diet and inhibition of the p38 MAPK (mitogen-activated protein kinase)/NFAT5 (nuclear factor of activated T-cells 5) signaling axis in STIA. Further experiments indicated a decreased leukodiapedesis under LS conditions. In conclusion, dietary salt restriction ameliorates CIA and STIA, indicating a beneficial role of LS diet during both the immunization and effector phase of immune-mediated arthritides by predominantly modulating the humoral immunity and the activation status of myeloid lineage cells. Hence, salt restriction might represent a supportive dietary intervention not only to reduce cardiovascular risk, but also to improve human inflammatory joint diseases like rheumatoid arthritis.
Engineering, Characterization, and Biological Evaluation of an Antibody Targeting the HGF Receptor
Authors: Desole Claudia , Gallo Simona , Vitacolonna Annapia , Vigna Elisa , Basilico Cristina , Montarolo Francesca , Zuppini Francesca , Casanova Elena , Miggiano Riccardo , Ferraris Davide Maria , Bertolotto Antonio , Comoglio Paolo Maria , Crepaldi Tiziana
Published: December 2021

The Hepatocyte growth factor (HGF) and its receptor (MET) promote several physiological activities such as tissue regeneration and protection from cell injury of epithelial, endothelial, neuronal and muscle cells. The therapeutic potential of MET activation has been scrutinized in the treatment of acute tissue injury, chronic inflammation, such as renal fibrosis and multiple sclerosis (MS), cardiovascular and neurodegenerative diseases. On the other hand, the HGF-MET signaling pathway may be caught by cancer cells and turned to work for invasion, metastasis, and drug resistance in the tumor microenvironment. Here, we engineered a recombinant antibody (RDO24) and two derived fragments, binding the extracellular domain (ECD) of the MET protein. The antibody binds with high affinity (8 nM) to MET ECD and does not cross-react with the closely related receptors RON nor with Semaphorin 4D. Deletion mapping studies and computational modeling show that RDO24 binds to the structure bent on the Plexin-Semaphorin-Integrin (PSI) domain, implicating the PSI domain in its binding to MET. The intact RDO24 antibody and the bivalent Fab2, but not the monovalent Fab induce MET auto-phosphorylation, mimicking the mechanism of action of HGF that activates the receptor by dimerization. Accordingly, the bivalent recombinant molecules induce HGF biological responses, such as cell migration and wound healing, behaving as MET agonists of therapeutic interest in regenerative medicine. In vivo administration of RDO24 in the murine model of MS, represented by experimental autoimmune encephalomyelitis (EAE), delays the EAE onset, mitigates the early clinical symptoms, and reduces inflammatory infiltrates. Altogether, these results suggest that engineered RDO24 antibody may be beneficial in multiple sclerosis and possibly other types of inflammatory disorders.
Belimumab for Immune-Mediated Necrotizing Myopathy Associated With Anti-SRP Antibodies: A Case Report and Retrospective Review of Patients Treated With Anti-B-Cell Therapy in a Single Center and Literature
Authors: Cui Bei-Bei , Tian Yun-Ru , Ma Xin-Yue , Yin Geng , Xie Qibing
Published: December 2021

Background

Immune-mediated necrotizing myopathy (IMNM) is characterized by markedly elevated creatinine kinase and histologically scattered necrotic muscle fibers and generally associated with autoantibodies against signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coA-reductase (HMGCR). Poor clinical response to conventional therapies and relapses commonly occur in severe cases. Anti-B-cell therapies have been used in refractory/relapsing cases.

Methods

The characteristics of a patient with IMNM associated with anti-SRP antibodies including physical examination, laboratory tests, and disease activity assessment were evaluated. Conventional therapy, belimumab treatment schedule, and follow-up data were recorded. Medical records of IMNM patients treated in our department from September 2014 to June 2021 were reviewed to evaluate the efficacy and safety of anti-B-cell therapy for anti-SRP IMNM. A literature review of patients with anti-SRP IMNM treated with anti-B-cell therapies was performed.

Results

We describe a case of a 47-year-old woman with IMNM associated with anti-SRP antibodies who relapsed twice after conventional therapy but showed good response and tolerance to belimumab at 28 weeks follow-up. In this review, three patients from our department were treated with rituximab. Two of the three patients rapidly improved after treatment. Twenty patients and five retrospective studies were included in the literature review. All patients were administered rituximab as an anti-B-cell drug.

Conclusion

Despite a lack of rigorous clinical trials, considerable experience demonstrated that anti-B-cell therapy might be effective for patients with IMNM associated with anti-SRP antibodies. Belimumab in association with steroids might be an encouraging option for refractory/relapsing cases.
Prognostic Stratification Based on HIF-1 Signaling for Evaluating Hypoxic Status and Immune Infiltration in Pancreatic Ductal Adenocarcinomas
Authors: Zhuang Hongkai , Wang Shujie , Chen Bo , Zhang Zedan , Ma Zuyi , Li Zhenchong , Liu Chunsheng , Zhou Zixuan , Gong Yuanfeng , Huang Shanzhou , Hou Baohua , Chen Yajin , Zhang Chuanzhao
Published: December 2021

Pancreatic ductal adenocarcinoma (PDAC) has a hypoxic and desmoplastic tumor microenvironment (TME), leading to treatment failure. We aimed to develop a prognostic classifier to evaluate hypoxia status and hypoxia-related molecular characteristics of PDAC. In this study, we classified PDAC into three clusters based on 16 known hypoxia-inducible factor 1 (HIF-1)-related genes. Nine differentially expressed genes were identified to construct an HIF-1 score system, whose predictive efficacy was evaluated. Furthermore, we investigated oncogenic pathways and immune-cell infiltration status of PDAC with different scores. The C-index of the HIF-1score system for OS prediction in the meta-PDAC cohort and the other two validation cohorts were 0.67, 0.63, and 0.65, respectively, indicating that it had a good predictive value for patient survival. Furthermore, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the HIF-1α score system for predicting 1-, 3-, and 4-year OS indicated the HIF-1α score system had an optimal discrimination of prognostic prediction for PDAC. Importantly, our model showed superior predictive ability compared to previous hypoxia signatures. We also classified PDAC into HIF-1 scores of low, medium, and high groups. Then, we found high enrichment of glycolysis, mTORC1 signaling, and MYC signaling in the HIF-1 score high group, whereas the cGMP metabolic process was activated in the low score group. Of note, analysis of public datasets and our own dataset showed a high HIF-1 score was associated with high immunosuppressive TME, evidenced by fewer infiltrated CD8+ T cells, B cells, and type 1 T-helper cells and reduced cytolytic activity of CD8+ T cells. In summary, we established a specific HIF-1 score system to discriminate PDAC with various hypoxia statuses and immune microenvironments. For highly hypoxic and immunosuppressive tumors, a combination treatment strategy should be considered in the future.
Increasing Knowledge Translation Capacity in Low- and Middle-Income Countries: A Model for Implementation Research Training
Authors: Penkunas Michael J. , Berdou Evangelia , Chong Shiau Y. , Launois Pascal , Rhule Emma L. M. , Allotey Pascale
Published: December 2021

Most health professionals lack the training and expertise to translate clinical innovations into actionable programs. Even though some public health expert communities understand that even widely proven solutions need to be adapted to the demands and characteristics of diverse health systems and societies to be successful, such knowledge has yet to inform routine public health approaches and practices. Therefore, it should not be a surprise that the “know-do” gap between clinical innovations and their on-the-ground application that implementation research seeks to bridge is pervasive and enduring, particularly in low- and middle-income countries. This article draws on a study of implementation research training courses to highlight the various competencies needed to translate different types of knowledge into action, many of which are not adequately addressed in existing curricula. We utilized a four-phase modified Delphi methodology that included a review of the academic and grey literature, one-on-one interviews with experts, virtual dialogue series with key stakeholders, and peer review of the synthesized results. The resulting areas in need of further development include the ability of learners to work as part of a multidisciplinary team, engage various stakeholders, and communicate research findings to decision-makers. Based on these insights, it is argued that knowledge translation in implementation research is a multi-faceted, multi-level sensemaking and communication activity that takes place throughout the research and research-to policy-processes.
210Po-210Pb Disequilibrium in the Western North Pacific Ocean: Particle Cycling and POC Export
Authors: Zhong Qiangqiang , Yu Tao , Lin Hui , Lin Jing , Ji Jianda , Ni Jialin , Du Jinzhou , Huang Dekun
Published: December 2021

Estimating the particulate organic carbon (POC) export flux from the upper ocean is fundamental for understanding the efficiency of the biological carbon pump driven by sinking particles in the oceans. The downward POC flux from the surface ocean based on 210Po-210Pb disequilibria in seawater samples from the western North Pacific Ocean (w-NPO) was measured in the early summer (May-June) of 2018. All the profiles showed a large 210Po deficiency relative to 210Pb in the euphotic zone (0–150 m), while this 210Po deficiency vanished below ∼500 m (with 210Po/210Pb ∼1 or > 1). A one-dimensional steady-state irreversible scavenging model was used to quantify the scavenging and removal fluxes of 210Po and 210Pb in the euphotic zone of the w-NPO. In the upper ocean (0–150 m), dissolved 210Po (D-Po) was scavenged into particles with a residence time of 0.6–5.5 year, and the 210Po export flux out of the euphotic zone was estimated as (0.33–3.49) × 104 dpm/m2/year, resulting in a wide range of particulate 210Po (P-Po) residence times (83–921 days). However, in the deep ocean (150–1,000 m), 210Po was transferred from the particulate phase to the dissolved phase. Using an integrated POC inventory and the P-Po residence times (Eppley model) in the w-NPO euphotic zone, the POC export fluxes (mmol C/m2/d) varied from 0.6 ± 0.2 to 8.8 ± 0.4. In comparison, applying the POC/210Po ratio of all (>0.45 μm) particles to 210Po export flux (Buesseler model), the obtained POC export fluxes (mmol C/m2/d) ranged from 0.7 ± 0.1 to 8.6 ± 0.8. Both Buesseler and Eppley methods showed enhanced POC export fluxes at stations near the continental shelf (i.e., Luzon Strait and the Oyashio-Kuroshio mixing region). The Eppley model-based 210Po-derived POC fluxes agreed well with the Buesseler model-based fluxes, indicating that both models are suitable for assessing POC fluxes in the w-NPO. The POC export efficiency was < 15%, suggesting a moderate biological carbon pump efficiency in the w-NPO. These low export efficiencies may be associated with the dominance of smaller particles and the processes of degradation and subsequent remineralization of these small particles in the euphotic zone of oligotrophic regions in the w-NPO.
Case Report: Two Cases of Abdominal Aggressive Fibromatosis That Mimicked Abdominal Wall Endometriosis and Review of Literature
Authors: Chen Xin , Wang Yuan , Liu Haiyuan , Shi Honghui , Fan Qingbo , Lang Jinghe
Published: December 2021

Background: Abdominal aggressive fibromatosis (AF) can be confounded with abdominal wall endomentriosis (AWE) because they share considerable similarity. Because of the different patient prognoses and treatment strategies available, accurate pre-operative diagnosis is important.

Case Presentation: We here report two cases of abdominal masses presenting as periodic changes in tumor sizes, which occurred in correlation with the menstrual cycle. The clinical findings were highly suggestive of AWE. However, the final pathological findings revealed AF. The estrogen receptor and progesterone receptor expressions were negative in the two cases. The differences between the two diseases have been discussed in detail.

Conclusion: A diagnosis of AWE should be scrutinized closely if the patient does not complain of cyclic pain. Fine-needle aspiration cytology is a suitable tool for pre-operative evaluation.
In silico Evolution and Comparative Genomic Analysis of IncX3 Plasmids Isolated From China Over Ten Years
Authors: Liu Baomo , Guo Yingyi , Liu Ningjing , Wang Jiong , Li Feifeng , Yao Likang , Zhuo Chao
Published: December 2021

IncX3 plasmids are correlated with the dissemination and acquisition of carbapenem resistance in Enterobacteriaceae and have been prevalent in China over the last 10 years. Since the distribution characteristics of IncX3 plasmids across China as well as their evolutionary traits for 10 years remain unclear, here we conducted a retrospective literature review and in silico comparative analysis of IncX3 plasmids in publicly available IncX3 plasmid genomes. IncX3 plasmids distributed in 17 provinces or cities were extracted for analysis, which tend to be specifically associated with hospital-isolated Escherichia coli ST410 from phylogroup A. Although the backbones of IncX3 plasmids have remained highly conservative over the last 10 years, the blaNDM resistance genetic contexts on these plasmids could fall into five subtypes, among which AR_N1_I has been identified in Enterobacter cloacae174 chromosome and AR_N5_I was simultaneously located on IncF and IncA/C plasmids. This suggests that the blaNDM resistance gene environment can spread between different plasmids, between different bacterial genera, or between strains and plasmids, highlighting that it is imperative to adopt more stringent infection control measures targeting IncX3 plasmid spread.
Cytokines and Chemokines in HBV Infection
Authors: Zhong Shihong , Zhang Tianling , Tang Libo , Li Yongyin
Published: December 2021

Chronic hepatitis B virus (HBV) infection remains a leading cause of hepatic inflammation and damage. The pathogenesis of chronic hepatitis B (CHB) infection is predominantly mediated by persistent intrahepatic immunopathology. With the characterization of unique anatomical and immunological structure, the liver is also deemed an immunological organ, which gives rise to massive cytokines and chemokines under pathogenesis conditions, having significant implications for the progression of HBV infection. The intrahepatic innate immune system is responsible for the formidable source of cytokines and chemokines, with the latter also derived from hepatic parenchymal cells. In addition, systemic cytokines and chemokines are disturbed along with the disease course. Since HBV is a stealth virus, persistent exposure to HBV-related antigens confers to immune exhaustion, whereby regulatory cells are recruited by intrahepatic chemokines and cytokines, including interleukin-10 and transforming growth factor β, are involved in such series of causal events. Although the considerable value of two types of available approved treatment, interferons and nucleos(t)ide analogues, effectively suppress HBV replication, neither of them is sufficient for optimal restoration of the immunological attrition state to win the battle of the functional or virological cure of CHB infection. Notably, cytokines and chemokines play a crucial role in regulating the immune response. They exert effects by directly acting on HBV or indirectly manipulating target immune cells. As such, specific cytokines and chemokines, with a potential possibility to serve as novel immunological interventions, combined with those that target the virus itself, seem to be promising prospects in curative CHB infection. Here, we systematically review the recent literature that elucidates cytokine and chemokine-mediated pathogenesis and immune exhaustion of HBV infection and their dynamics triggered by current mainstream anti-HBV therapy. The predictive value of disease progression or control and the immunotherapies target of specific major cytokines and chemokines in CHB infection will also be delineated.
Neural Stem Cells Overexpressing Nerve Growth Factor Improve Functional Recovery in Rats Following Spinal Cord Injury via Modulating Microenvironment and Enhancing Endogenous Neurogenesis
Authors: Wang Lei , Gu Sujie , Gan Jinlu , Tian Yi , Zhang Fangcheng , Zhao Hongyang , Lei Deqiang
Published: December 2021

Spinal cord injury (SCI) is a devastating event characterized by severe motor, sensory, and autonomic dysfunction. Currently, there is no effective treatment. Previous studies showed neural growth factor (NGF) administration was a potential treatment for SCI. However, its targeted delivery is still challenging. In this study, neural stem cells (NSCs) were genetically modified to overexpress NGF, and we evaluated its therapeutic value following SCI. Four weeks after transplantation, we observed that NGF-NSCs significantly enhanced the motor function of hindlimbs after SCI and alleviated histopathological damage at the lesion epicenter. Notably, the survival NGF-NSCs at lesion core maintained high levels of NGF. Further immunochemical assays demonstrated the graft of NGF-NSCs modulated the microenvironment around lesion core via reduction of oligodendrocyte loss, attenuation of astrocytosis and demyelination, preservation of neurons, and increasing expression of multiple growth factors. More importantly, NGF-NSCs seemed to crosstalk with and activate resident NSCs, and high levels of NGF activated TrkA, upregulated cAMP-response element binding protein (CREB) and microRNA-132 around the lesion center. Taken together, the transplantation of NGF-NSCs in the subacute stage of traumatic SCI can facilitate functional recovery by modulating the microenvironment and enhancing endogenous neurogenesis in rats. And its neuroprotective effect may be mediated by activating TrkA, up-regulation of CREB, and microRNA-132.
Improving Between-Group Effect Size for Multi-Site Functional Connectivity Data via Site-Wise De-Meaning
Authors: Reardon Alexandra M. , Li Kaiming , Hu Xiaoping P.
Published: December 2021

Background: Multi-site functional MRI (fMRI) databases are becoming increasingly prevalent in the study of neurodevelopmental and psychiatric disorders. However, multi-site databases are known to introduce site effects that may confound neurobiological and measures such as functional connectivity (FC). Although studies have been conducted to mitigate site effects, these methods often result in reduced effect size in FC comparisons between controls and patients.

Methods: We present a site-wise de-meaning (SWD) strategy in multi-site FC analysis and compare its performance with two common site-effect mitigation methods, i.e., generalized linear model (GLM) and Combining Batches (ComBat) Harmonization. For SWD, after FC was calculated and Fisher z-transformed, the site-wise FC mean was removed from each subject before group-level statistical analysis. The above methods were tested on two multi-site psychiatric consortiums [Autism Brain Imaging Data Exchange (ABIDE) and Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP)]. Preservation of consistent FC alterations in patients were evaluated for each method through the effect sizes (Hedge’s g) of patients vs. controls.

Results: For the B-SNIP dataset, SWD improved the effect size between schizophrenic and control subjects by 4.5–7.9%, while GLM and ComBat decreased the effect size by 22.5–42.6%. For the ABIDE dataset, SWD improved the effect size between autistic and control subjects by 2.9–5.3%, while GLM and ComBat decreased the effect size by up to 11.4%.

Conclusion: Compared to the original data and commonly used methods, the SWD method demonstrated superior performance in preserving the effect size in FC features associated with disorders.
Effect of Robot-Assisted Neuroendoscopic Hematoma Evacuation Combined Intracranial Pressure Monitoring for the Treatment of Hypertensive Intracerebral Hemorrhage
Authors: Wu Shiqiang , Wang Heping , Wang Junwen , Hu Feng , Jiang Wei , Lei Ting , Shu Kai
Published: December 2021

Objective: This study aimed to investigate the clinical efficacy of robot-assisted neuroendoscopic hematoma evacuation combined intracranial pressure (ICP) monitoring for the treatment of hypertensive intracerebral hemorrhage (HICH).

Patients and Methods: A retrospective analysis of 53 patients with HICH undergoing neuroendoscopic hematoma evacuation in our department from January 2016 to December 2020 was performed. We divided the patients into two groups: the neuroendoscopic group (n = 32) and the robot-assisted neuroendoscopic combined ICP monitoring group (n = 21). Data on clinical characteristics, treatment effects, and outcomes were retrospectively reviewed and analyzed between these two groups.

Results: The operation time of the procedure of the neuroendoscopic group was significantly longer than that of the robot-assisted neuroendoscopic combined ICP-monitoring group (mean time 153.8 ± 16.8 vs. 132.8 ± 15.7 min, P < 0.001). The intraoperative blood loss was significantly less in the robot-assisted neuroendoscopic combined ICP-monitoring group than in the neuroendoscopic group (215.4 ± 28.3 vs. 190.1 ± 25.6 ml, P = 0.001). However, the patients undergoing neuroendoscopic had a comparable hematoma clearance rate with those undergoing robot-assisted neuroendoscopic combined ICP monitoring (85.2 ± 4.8 vs. 89.2 ± 5.4%, P = 0.997). The complications rate was greater in the endoscopic group (25%) than in the robot-assisted neuroendoscopic combined ICP-monitoring group (9.5%) but without significant difference (P = 0.159). We also found that the dose of used mannitol was significantly less in the ICP monitoring group (615.2 ± 63.8 vs. 547.8 ± 65.3 ml, P < 0.001) and there was a significant difference in modified Rankin scale (mRS) score at discharge, patients with less mRS score in the robot-assisted neuroendoscopic combined ICP monitoring group than in the neuroendoscopic group (3.0 ± 1.0 vs. 3.8 ± 0.8, p = 0.011). Patients undergoing robot-assisted neuroendoscopic combined ICP monitoring had better 6-month functional outcomes, and there was a significant difference between the two groups (p = 0.004). Besides, multivariable analysis shows younger age, no complication, and robot-assisted neuroendoscopic combined ICP monitoring were predictors of 6-month favorable outcomes for the patients with HICH.

Conclusion: Robot-assisted neuroendoscopic hematoma evacuation combined with ICP monitoring appears to be safer and more effective as compared to the neuroendoscopic hematoma evacuation in the treatment of HICH. Robot-assisted neuroendoscopic hematoma evacuation combined with ICP monitoring might improve the clinical effect and treatment outcomes of the patients with HICH.
Prediction of Post-operative Visual Deterioration Using Visual-Evoked Potential Latency in Extended Endoscopic Endonasal Resection of Craniopharyngiomas
Authors: Tao Xiaorong , Yang Xiaocui , Fan Xing , You Hao , Jin Yanwen , Liu Jiajia , Guo Dongze , Li Chuzhong , Qiao Hui
Published: December 2021

Background: The current study aimed to investigate the predictive value of visual-evoked potential (VEP) latency for post-operative visual deterioration in patients undergoing craniopharyngioma resection via extended endoscopic endonasal approach (EEEA).

Methods: Data from 90 patients who underwent craniopharyngioma resection via EEEA with intraoperative VEP monitoring were retrospectively reviewed. P100 latency was compared between patients with and without post-operative visual deterioration, and the threshold value of P100 latency for predicting post-operative visual deterioration was calculated by the receiver operating characteristic curve analysis. In addition, other potential prognostic factors regarding post-operative visual outcomes were also analyzed by multivariate analysis.

Results: Patients with post-operative visual deterioration showed a significantly longer VEP latency than those without (p < 0.001). An extension over 8.61% in VEP latency was identified as a predictor of post-operative visual deterioration (p < 0.001). By contrast, longer preoperative visual impairment duration and larger tumor volume were not significant predictors for post-operative visual deterioration.

Conclusions: The current study revealed that intraoperative VEP monitoring in EEEA is effective for predicting post-operative visual deterioration, and an extension over 8.61% in VEP latency can be used as a critical cut-off value to predict post-operative visual deterioration.
Evolutionary Origins of the Oligodendrocyte Cell Type and Adaptive Myelination
Authors: Hines Jacob H.
Published: December 2021

Oligodendrocytes are multifunctional central nervous system (CNS) glia that are essential for neural function in gnathostomes. The evolutionary origins and specializations of the oligodendrocyte cell type are among the many remaining mysteries in glial biology and neuroscience. The role of oligodendrocytes as CNS myelinating glia is well established, but recent studies demonstrate that oligodendrocytes also participate in several myelin-independent aspects of CNS development, function, and maintenance. Furthermore, many recent studies have collectively advanced our understanding of myelin plasticity, and it is now clear that experience-dependent adaptations to myelination are an additional form of neural plasticity. These observations beg the questions of when and for which functions the ancestral oligodendrocyte cell type emerged, when primitive oligodendrocytes evolved new functionalities, and the genetic changes responsible for these evolutionary innovations. Here, I review recent findings and propose working models addressing the origins and evolution of the oligodendrocyte cell type and adaptive myelination. The core gene regulatory network (GRN) specifying the oligodendrocyte cell type is also reviewed as a means to probe the existence of oligodendrocytes in basal vertebrates and chordate invertebrates.