bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti
Authors: Chand Meenal , Choi Jae-Yeon , Pal Anasuya C. , Singh Pallavi , Kumari Vandana , Thekkiniath Jose , Gagnon Jacqueline , Timalsina Sushma , Gaur Gauri , Williams Scott , Ledizet Michel , Mamoun Choukri Ben 
Published: November 2022

The significant rise in the number of tick-borne diseases represents a major threat to public health worldwide. One such emerging disease is human babesiosis, which is caused by several protozoan parasites of the Babesia genus of which B. microti is responsible for most clinical cases reported to date. Recent studies have shown that during its intraerythrocytic life cycle, B. microti exports several antigens into the mammalian host using a novel vesicular-mediated secretion mechanism. One of these secreted proteins is the immunodominant antigen BmGPI12, which has been demonstrated to be a reliable biomarker of active B. microti infection. The major immunogenic determinants of this antigen remain unknown. Here we provide a comprehensive molecular and serological characterization of a set of eighteen monoclonal antibodies developed against BmGPI12 and a detailed profile of their binding specificity and suitability in the detection of active B. microti infection. Serological profiling and competition assays using synthetic peptides identified five unique epitopes on the surface of BmGPI12 which are recognized by a set of eight monoclonal antibodies. ELISA-based antigen detection assays identified five antibody combinations that specifically detect the secreted form of BmGPI12 in plasma samples from B. microti-infected mice and humans but not from other Babesia species or P. falciparum.
Gut microbiome and fecal metabolic alteration in systemic lupus erythematosus patients with depression
Authors: Yao Han , Yang Hao , Wang Yueying , Xing Qian , Yan Lin , Chai Yaru 
Published: November 2022

BackgroundMental health disorders in systemic lupus erythematosus (SLE) are gradually getting recognized; however, less is known regarding the actual structure and compositional alterations in gut microbiome and metabolism and the mechanisms of how they affect depression development in SLE patients.MethodsTwenty-one SLE patients with depression (SLE-d), 17 SLE patients without depression (SLE-nd), and 32 healthy controls (HC) were included in this study. Fecal samples were collected for 16S rRNA gene sequencing and ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) based metabolomics.ResultsThe structure of gut microbiome in the SLE-d group changed compared with that in the other two groups. The microbiome composition of SLE-d group showed decreased species richness indices, characterized by low ACE and Chao1 indices, a decrease in the ratio of phylum Firmicutes to Bacteroidetes, genus Faecalibacterium and Roseburia. A downregulation of the metabolite fexofenadine involved in bile secretion was positively correlated with the genus Faecalibacterium, Subdoligranulum and Agathobacter. Compared with the SLE-nd group, the SLE-d group had elevated serum levels of IL-2 and IL-6 and decreased BDNF. Interestingly, abundance of the genus Faecalibacterium and Roseburia was negatively correlated with IL-6, abundance of the genus Roseburia was negatively correlated with IL-2, and abundance of the genus Bacteroides was positively correlated with IL-2.ConclusionThis study identified specific fecal microbes and their metabolites that may participate in the development of SLE-d. Our findings provide a new perspective for improving depression in SLE patients by regulating the gut–brain axis.
Case report: Successful treatment of human diabetic foot ulcer using low-intensity diagnostic ultrasound combined with microbubbles: Two cases
Authors: Zhang Xiaojuan , Cheng Ying , Pei Ling , Tao Jie , Wang Rui , Chen Zhong 
Published: November 2022

BackgroundDiabetic foot ulcer (DFU) is one of the serious complications of diabetes, which has high disability rate and mortality. Low-intensity ultrasound combined with microbubbles in blood circulation can enhance the blood perfusion effect of local soft tissue, which has the potential to promote the healing of diabetic ulcer. Here, we report how this method was used to help the healing of two patients with chronic refractory DFUs.Case PresentationIn case 1, a 56-year-old man with 3-years history of type 2 diabetes had a 3.0×2.0 cm ulcer which infected with staphylococcus aureus on his right calf for more than half a month. In case 2, a 70-year-old man with 10-years history of type 2 diabetes presented with an 8-month right heel ulcer that developed to 7.5×4.6 cm. And he also had hyperlipidemia, hypertension, and renal impairment. Both patients were enrolled in our study to receive treatment of low-intensity diagnostic ultrasound (LIDUS) combined with microbubbles. They were discharged after a 20-minute daily standard treatment for 7 consecutive days. The ulcers in both cases completely healed in 60 days and 150 days, respectively, and haven’t recurred for more than one year of follow-up.ConclusionIt is feasible, safe, and effective to use commercial LIDUS combined with commercial microbubbles in the treatment of diabetic lower extremity ulcers. This study may provide an innovative and non-invasive method for the treatment of DFUs.
An assessment of future tidal marsh resilience in the San Francisco Estuary through modeling and quantifiable metrics of sustainability
Authors: Morris James T. , Drexler Judith Z. , Vaughn Lydia J. S. , Robinson April H. 
Published: November 2022

Quantitative, broadly applicable metrics of resilience are needed to effectively manage tidal marshes into the future. Here we quantified three metrics of temporal marsh resilience: time to marsh drowning, time to marsh tipping point, and the probability of a regime shift, defined as the conditional probability of a transition to an alternative super-optimal, suboptimal, or drowned state. We used organic matter content (loss on ignition, LOI) and peat age combined with the Coastal Wetland Equilibrium Model (CWEM) to track wetland development and resilience under different sea-level rise scenarios in the Sacramento-San Joaquin Delta (Delta) of California. A 100-year hindcast of the model showed excellent agreement (R2 = 0.96) between observed (2.86 mm/year) and predicted vertical accretion rates (2.98 mm/year) and correctly predicted a recovery in LOI (R2 = 0.76) after the California Gold Rush. Vertical accretion in the tidal freshwater marshes of the Delta is dominated by organic production. The large elevation range of the vegetation combined with high relative marsh elevation provides Delta marshes with resilience and elevation capital sufficiently great to tolerate centenary sea-level rise (CLSR) as high as 200 cm. The initial relative elevation of a marsh was a strong determinant of marsh survival time and tipping point. For a Delta marsh of average elevation, the tipping point at which vertical accretion no longer keeps up with the rate of sea-level rise is 50 years or more. Simulated, triennial additions of 6 mm of sediment via episodic atmospheric rivers increased the proportion of marshes surviving from 51% to 72% and decreased the proportion drowning from 49% to 28%. Our temporal metrics provide critical time frames for adaptively managing marshes, restoring marshes with the best chance of survival, and seizing opportunities for establishing migration corridors, which are all essential for safeguarding future habitats for sensitive species.
High-speed rail effects on station area-level business commercial agglomeration: Evidence from 110 stations in China
Authors: Liang Pengpeng , Cui Xu , Lin Mao , Yang Tian , Wu Bo 
Published: November 2022

As a critical transportation infrastructure, high-speed rail (HSR) greatly enhances accessibility and shortens the spatial-temporal distance among cities. It is well documented that HSR significantly impacts regions and cities’ economic development and spatial structure. The proportion and frequency of business passenger trips are increasing yearly, and the demand for “station as the final destination” is becoming more and more prominent. Given the pivotal role of the design and construction of HSR station areas in achieving “station as the final destination,” the study of their development characteristics and patterns has important implications for urban planning. Previous studies have focused extensively on the macro impact of the HSR operation on regional economies, urban industries, and tourism development, whereas only a few were conducted at the station level. Furthermore, the business-commercial agglomeration effects of the HSR operation on the development and construction of station areas have neither been studied nor accurately measured. To fill this gap, we first constructed a panel data set consisting of the point of interest (POI) data, China City Statistical Yearbook data, and the HSR station operation data from 2012 to 2017. Next, we developed difference-in-differences (DID) models to decipher the impact of the HSR operation on the station-level business and commercial agglomeration. The results show that the HSR operation has increased the business-commercial agglomeration index (BCAI), the commercial agglomeration index (BAI), and the business agglomeration index (CAI) by 28.3%, 29%, and 21.3%, respectively. In other words, the HSR operation has significant business-commercial agglomeration effects in the station area, and the agglomeration effect size of business is more extensive than that of commerce. Interestingly, the BCAI grew slowly in the first 3 years after the HSR operation but started to rise much faster from the fourth year, which HSR’s catalytic effects can explain. The results also reveal that the business-commercial agglomeration effects have a clear spatial threshold as the BCAI tends to decrease from 1500 m to 3000 m away from HSR stations. The plausibility of the results has been confirmed by the parallel trend, placebo, and robustness tests.
Lost to follow up from chronic care services during COVID-19 from health facilities, in Northwest Ethiopia
Authors: Belay Daniel Gashaneh , Adugna Asmamaw 
Published: November 2022

IntroductionThe COVID-19 pandemic and the responses to it have greatly altered individual lives, particularly those with chronic illnesses. The pandemic affected the processes of routine comprehensive care for patients. Because chronic illnesses depress the immune system, they make individuals more susceptible to infection as well as more sickly and less likely to recover from the COVID-19 pandemic. Because of this, the rate of loss to follow-up (LTFU) from chronic illness care is accelerated by the COVID-19 pandemic, and the number of patients receiving new treatments is decreased. Therefore this study aimed to assess the mean difference of loss to follow-up among HIV/AIDS, diabetes mellitus (DM), and hypertension patients during the COVID-19 period as compared to pre-COVID-19 at health facilities in Northwest Ethiopia.MethodsAn institution-based secondary data analysis of the Gondar city health report from October 2019 to Jun 2021 was done. Excel data were transformed to STATA 14 for analysis. An independent t-test was used to compare the mean difference of loss to follow-up and new initiation of treatment among HIV/AIDS, DM, and hypertension patients during the pre-COVID-19 and COVID-19 periods at facilities in Northwest Ethiopia. Variables with a mean difference of p &lt; 0.005 with a 95% confidence interval were used to declare the significant level.ResultThere was a significantly higher mean difference in the number of patients with LTFU from Anti-Retroviral Therapy (ART) and antihypertensive treatment during COVID-19 as compared to the pre-COVID-19 period [μd =17.85, 95%CI: 3.25, 32.95] and [μd =17.31, 95%CI: 8.35, 26.97] respectively. The mean number of patients who were newly started anti-hypertensive treatment during the COVID-19 season was significantly decreased as compared to those who were before the COVID-19 period [μd = −32.94, 95%CI: −63.76, −2.12].ConclusionThere was a significantly higher mean difference in the number of patients with LTFU from Anti-Retroviral Therapy (ART) and antihypertensive treatment during COVID-19 as compared to the pre-COVID-19 period. The mean number of patients who were newly started anti-hypertensive treatment during the COVID-19 season was significantly decreased as compared to the pre-COVID-19 period. Therefore the Ministry of Health Ethiopia (MOH) should update and prepare convenient care and follow-up such as remote chronic illness management methods during the ongoing COVID-19 pandemic in Ethiopia.
Interpreting spatially explicit variation in dietary proxies through species distribution modeling reveals foraging preferences of mammoth (Mammuthus) and American mastodon (Mammut americanum)
Authors: Pardi Melissa I. , DeSantis Larisa R. G. 
Published: November 2022

IntroductionThe end Pleistocene was a time of considerable ecological upheaval. Recent work has explored the megafauna extinction’s role in altering ecosystem processes. Analyses of functional traits withing communities reveal hidden consequences of the megafauna extinction beyond declines in taxonomic diversity. Functional diversity analyses offer new insight into our understanding of past ecosystems and may even inform future rewilding efforts. However, the utility of functional diversity may be hampered by the use of discrete, taxon-level functional traits, such as dietary categories, that mask variation in functional diversity over space and time.MethodsWe present an approach in which species distribution modeling, in Maxent, provides context for interpreting variation in two widely used proxies for diet among fossil taxa: stable isotope analysis and dental microwear texture analysis. We apply this approach to two ecologically distinct taxa, the American mastodon (Mammut americanum) and mammoths (Mammuthus) and investigate their resource use over space and time from the last glacial maximum to the end Pleistocene (25–11.7 thousand years before present).ResultsMammoth dietary behavior varies by context across their geographic distribution, despite possessing evolutionary adaptations that facilitate grazing. Mammoths exhibit a preference for grazing where species distribution modeling predicts the highest likelihood of occurrence but engage in more mixed-feeding outside of core likelihood areas. In contrast, dietary preferences for mastodon are less resolved and our analyses were unable to identify significant differences in diet across their distribution.DiscussionThe ecological roles of some species are context specific and need to be critically evaluated when planning for management of reintroductions or introducing novel species to restore lost ecological function.
Characterization of intrahepatic B cells in acute-on-chronic liver failure
Authors: Zhao Yudong , He Wei , Wang Chenchen , Cui Nana , Yang Changjie , You Zhengrui , Shi Bisheng , Xia Lei , Chen Xiaosong 
Published: November 2022

Background and objectivesAcute on chronic liver failure (ACLF) is characterized by the immunologic dissonance during the prolonged pathogenic development. Both abnormal innate immune response and adaptive T-cell response have been reported in patients with ACLF; however, less is known regarding B cells in ACLF pathogenesis. Previous reports were only based on immunophenotyping of peripheral blood samples. Here, we aim to dissect liver-infiltrating B-cell subpopulation in ACLF.MethodsPaired liver perfusate and peripheral blood were freshly collected from healthy living donors and recipients during liver transplantation. Liver tissues were obtained from patients with ACLF, cirrhosis, and healthy controls. Flow cytometry was used to characterize the phenotypic and functional alterations in intrahepatic and circulating B-cell populations from ACLF, cirrhosis, and healthy controls. The expression of CD19+ and CD138+ on liver tissues was examined by immunohistochemistry staining.ResultsIn this study, we first deciphered the intrahepatic B cells subsets of patients with ACLF. We found that the ACLF liver harbored reduced fraction of naïve B cells and elevated percentage of CD27+CD21− activated memory B cells (AM), CD27−CD21− atypical memory B cells (atMBC), CD27+IgD−IgM+(IgM+ memory B cells), and CD27+CD38++ plasma cells than cirrhosis and healthy controls. Moreover, these B subpopulations demonstrated enhanced activation and altered effector functions. Specifically, the ACLF liver was abundant in atMBC expressing higher CD11c and lower CD80 molecule, which was significantly correlated to alanine aminotransferase and aspartate aminotransferase. In addition, we found that intrahepatic CD27+CD38++plasma cells were preferentially accumulated in ACLF, which expressed more CD273 (PD-L2) and secreted higher granzyme B and IL-10. Finally, the enriched hepatic plasma B cells were in positive association with disease severity indices including alkaline phosphatase and gamma-glutamyl transferase.ConclusionsIn this pilot study, we showed an intrahepatic B-cell landscape shaped by the ACLF liver environment, which was distinct from paired circulating B-cell subsets. The phenotypic and functional perturbation in atMBC and plasma cells highlighted the unique properties of infiltrating B cells during ACLF progression, thereby denoting the potential of B-cell intervention in ACLF therapy.
Development of a polyamine gene expression score for predicting prognosis and treatment response in clear cell renal cell carcinoma
Authors: Chen Mei , Nie Zhenyu , Huang Denggao , Gao Yuanhui , Cao Hui , Zheng Linlin , Zhang Shufang 
Published: November 2022

BackgroundsPolyamine metabolism (PM) is closely related to the tumor microenvironment (TME) and is involved in antitumor immunity. Clear cell renal cell carcinoma (ccRCC) not only has high immunogenicity but also has significant metabolic changes. However, the role of PM in the immune microenvironment of ccRCC remains unclear. This study aimed to reveal the prognostic value of PM-related genes (PMRGs) expression in ccRCC and their correlation with the TME.MethodsThe expression levels PMRGs in different cells were characterized with single-cell sequencing analysis. The PMRG expression pattern of 777 ccRCC patients was evaluated based on PMRGs. Unsupervised clustering analysis was used in identifying PMRG expression subtypes, and Lasso regression analysis was used in developing polyamine gene expression score (PGES), which was validated in external and internal data sets. The predictive value of PGES for immunotherapy was validated in the IMvigor210 cohort. Multiple algorithms were used in analyzing the correlation between PGES and immune cells. The sensitivity of PGES to chemotherapeutic drugs was analyzed with the “pRRophetic” package. We validated the genes that develop PGES in tissue samples. Finally, weighted gene co-expression network analysis was used in identifying the key PMRGs closely related to ccRCC, and cell function experiments were carried out.ResultsPMRGs were abundantly expressed on tumor cells, and PMRG expression was active in CD8+ T cells and fibroblasts. We identified three PMRG expression subtypes. Cancer and immune related pathways were active in PMRG expression cluster A, which had better prognosis. PGES exhibited excellent predictive value. The high-PGES group was characterized by high immune cell infiltration, high expression of T cell depletion markers, high tumor mutation burden and tumor immune dysfunction and exclusion, was insensitive to immunotherapy but sensitive to sunitinib, temsirolimus, and rapamycin, and had poor prognosis. Spermidine synthetase (SRM) has been identified as a key gene and is highly expressed in ccRCC at RNA and protein levels. SRM knockdown can inhibit ccRCC cell proliferation, migration, and invasion.ConclusionsWe revealed the biological characteristics of PMRG expression subtypes and developed PGES to accurately predict the prognosis of patients and response to immunotherapy.
Knockout of IL-6 mitigates cold water-immersion restraint stress-induced intestinal epithelial injury and apoptosis
Authors: Zhang Yuan , Duan Chujun , Wu Shuwen , Ma Jingchang , Liu Yongming , Li Wenpeng , Wang Tingting , Yang Lu , Cheng Kun , Zhuang Ran 
Published: November 2022

BackgroundInterleukin-6 (IL-6) is essential for maintaining intestinal epithelial homeostasis. Although cold water-immersion restraint (CWIR) stress is commonly used to induce in vivo gastric injury, it also affects intestinal epithelial permeability. Although IL-6 is increased in response to acute physiological and psychological stress, its exact effects on the pathophysiology of the intestinal epithelium in response to acute CWIR stress remain unknown.MethodsWe used IL-6 knockout (KO) mice with acute CWIR modeling to investigate the effect of IL-6 deficiency on intestinal epithelial morphology and pathological damage using histological staining assays under the acute stress. We detected jejunal epithelial apoptosis using TUNEL and standard molecular experiments.ResultsCWIR caused intestinal epithelial damage, which was alleviated by the absence of IL-6, as evidenced by morphological changes and goblet cell and intestinal permeability alteration. IL-6 KO also reduced CWIR-mediated inflammatory levels and improved stress defense. Meanwhile, IL-6 deficiency decreased the intestinal epithelial apoptosis induced by CWIR administration. This IL-6 KO-led effect depended more on mitochondrial AIF signaling rather than the traditional caspase pathway.ConclusionAs a result, we concluded that acute CWIR-induced severe intestinal damage and jejunal epithelium apoptosis could be alleviated by IL-6 deficiency, implying a protective effect of IL-6 deficiency on the intestines under acute stress. The findings shed new light on treating CWIR-induced intestinal disorders by inhibiting IL-6 signaling.
Genomic analysis of TNF-related genes with prognosis and characterization of the tumor immune microenvironment in lung adenocarcinoma
Authors: Huang Hua , Yu Haochuan , Li Xuanguang , Li Yongwen , Zhu Guangsheng , Su Lianchun , Li Mingbiao , Chen Chen , Gao Min , Wu Di , Zhang Ruihao , Cao Peijun , Liu Hongyu , Chen Jun 
Published: November 2022

BackgroundThe tumor necrosis factor (TNF) family plays a role in modulating cellular functions that regulate cellular differentiation, survival, apoptosis, and especially cellular immune functions. The TNF family members also play important roles in oncogenesis and progression. However, the potential role of the TNF family members in lung adenocarcinoma (LUAD) is yet to be explored.MethodsThe expression of TNF-related genes (TNFRGs) in 1,093 LUAD samples was investigated using The Cancer Genome Atlas and Gene Expression Omnibus datasets. The characteristic patterns of TNFRGs in LUAD were systematically probed and three distinct molecular subtypes were identified. Furthermore, a correlation was found between the different subtypes and their clinical characteristics. A TNF scoring system was created to predict overall survival (OS) and therapeutic responses in patients with LUAD. Subsequently, the predictive accuracy of the score was verified and a nomogram was used to optimize the clinical applicability range of the TNF score.ResultsA high TNF score, involving the immune and stromal scores, indicated negative odds of OS. Moreover, the TNF score was associated with immune checkpoints and chemotherapeutic drug sensitivity. Collectively, our comprehensive TNFRGs analysis of patients with LUAD revealed that TNF could be involved in forming the diverse and complex tumor microenvironment, its clinicopathological features, and its prognosis.ConclusionsA TNF-related prognostic model was constructed, and a TNF score was developed. These findings are expected to improve our knowledge regarding the function of TNFRGs in LUAD, pave a new path for assessing the disease prognosis, and assist in developing personalized therapeutic strategies for patients with LUAD.