bluuebunny/crossref_metadata_2025 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

Background

Mental 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.

Methods

Twenty-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.

Results

The 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.

Conclusion

This 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

Background

Diabetic 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 Presentation

In 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.

Conclusion

It 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

Introduction

The 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.

Methods

An 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 < 0.005 with a 95% confidence interval were used to declare the significant level.

Result

There 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].

Conclusion

There 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

Introduction

The 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.

Methods

We 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).

Results

Mammoth 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.

Discussion

The 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.
Clinical genetics of spondylocostal dysostosis: A mini review
Authors: Umair Muhammad , Younus Muhammad , Shafiq Sarfraz , Nayab Anam , Alfadhel Majid
Published: November 2022

Spondylocostal dysostosis is a genetic defect associated with severe rib and vertebrae malformations. In recent years, extensive clinical and molecular diagnosis advancements enabled us to identify disease-causing variants in different genes for such severe conditions. The identification of novel candidate genes enabled us to understand the developmental biology and molecular and cellular mechanisms involved in the etiology of these rare diseases. Here, we discuss the clinical and molecular targets associated with spondylocostal dysostosis, including clinical evaluation, genes, and pathways involved. This review might help us understand the basics of such a severe disorder, which might help in proper clinical characterization and help in future therapeutic strategies.
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 objectives

Acute 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.

Methods

Paired 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.

Results

In 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.

Conclusions

In 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.
HIV-1 infected humanized DRAGA mice develop HIV-specific antibodies despite lack of canonical germinal centers in secondary lymphoid tissues
Authors: Ollerton Matthew T. , Folkvord Joy M. , Peachman Kristina K. , Shashikumar Soumya , Morrison Elaine B. , Jagodzinski Linda L. , Peel Sheila A. , Khreiss Mohammad , D’Aquila Richard T. , Casares Sofia , Rao Mangala , Connick Elizabeth
Published: November 2022

A major barrier in the use of humanized mice as models of HIV-1 (HIV) infection is the inadequate generation of virus-specific antibody responses. Humanized DRAGA (hDRAGA) mice generate antigen-specific class switched antibodies to several pathogens, but whether they do so in HIV infection and the extent to which their secondary lymphoid tissues (sLT) support germinal center responses is unknown. hDRAGA mice were evaluated for their ability to support HIV replication, generate virus-specific antibody responses, develop splenocyte subsets, and organize sLT architecture. hDRAGA mice supported persistent HIV replication and developed modest levels of gp41-specific human IgM and IgG. Spleens from uninfected and HIV infected hDRAGA mice contained differentiated B and CD4+T cell subsets including germinal center (GC) B cells and T follicular helper cells (TFH); relative expansions of TFH and CD8+T cells, but not GC B cells, occurred in HIV-infected hDRAGA mice compared to uninfected animals. Immunofluorescent staining of spleen and mesenteric lymph node sections demonstrated atypical morphology. Most CD4+and CD8+T cells resided within CD20hiareas. CD20hiareas lacked canonical germinal centers, as defined by staining for IgD-Ki67+cells. No human follicular dendritic cells (FDC) were detected. Mouse FDC were distributed broadly throughout both CD20hiand CD20loregions of sLT. HIV RNA particles were detected byin situhybridization within CD20+areas and some co-localized with mouse FDC. Viral RNA+cells were more concentrated within CD20hicompared to CD20loareas of sLT, but differences were diminished in spleen and eliminated in mesenteric lymph nodes when adjusted for CD4+cell frequency. Thus, hDRAGA mice recapitulated multiple aspects of HIV pathogenesis including HIV replication, relative expansions in TFH and CD8+T cells, and modest HIV-specific antibody production. Nevertheless, classical germinal center morphology in sLT was not observed, which may account for the inefficient expansion of GC B cells and generation of low titer human antibody responses to HIV-1 in this model.
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

Backgrounds

Polyamine 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.

Methods

The 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.

Results

PMRGs 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.

Conclusions

We revealed the biological characteristics of PMRG expression subtypes and developed PGES to accurately predict the prognosis of patients and response to immunotherapy.
Intestinal Gasdermins for regulation of inflammation and tumorigenesis
Authors: Gong Wenbin , Yang Kui , Zhao Wei , Zheng Jianbao , Yu Junhui , Guo Kun , Sun Xuejun
Published: November 2022

Gasdermins (GSDMs) protein family express in intestinal epithelial cells or lamina propria immune cells, and play a nonnegligible function during gut homeostasis. With the gradually in-depth investigation of GSDMs protein family, the proteases that cleave GSDMA-E have been identified. Intestinal GSDMs-induced pyroptosis is demonstrated to play a crucial role in the removal of self-danger molecules and clearance of pathogenic organism infection by mediating inflammatory reaction and collapsing the protective niche for pathogens. Simultaneously, excessive pyroptosis leading to the release of cellular contents including inflammatory mediators into the extracellular environment, enhancing the mucosal immune response. GSDMs-driver pyroptosis also participates in a novel inflammatory cell death, PANoptosis, which makes a significant sense to the initiation and progression of gut diseases. Moreover, GSDMs are expressed in healthy intestinal tissue without obvious pyroptosis and inflammation, indicating the potential intrinsic physiological functions of GSDMs that independent of pyroptotic cell death during maintenance of intestinal homeostasis. This review provides an overview of the latest advances in the physiological and pathological properties of GSDMs, including its mediated pyroptosis, related PANoptosis, and inherent functions independent of pyroptosis, with a focus on their roles involved in intestinal inflammation and tumorigenesis.
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

Background

Interleukin-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.

Methods

We 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.

Results

CWIR 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.

Conclusion

As 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

Background

The 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.

Methods

The 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.

Results

A 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.

Conclusions

A 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.
Early to mid-Holocene sedimentary environmental evolution in the palaeo-Ningbo Bay, East China and its implications for Neolithic coastal settlement
Authors: Lyu Ye , Xu Hao , Meadows Michael E. , Wang Zhanghua
Published: November 2022

The Ningbo Plain on the East China coast is an important center of Neolithic culture, and associated settlements were influenced by changing sea levels and the geomorphological and hydrological environments of the palaeo-Ningbo Bay, the details of which are still subject to debate. This study is based on two well-dated sediment cores obtained from the Ningbo Plain, and here we report analyses of their sedimentology and foraminifera to reveal the infilling history of the palaeo-Ningbo Bay and its association with Neolithic occupation. The lithology of the largely muddy sediments and the dominance of euryhaline and brackish water foraminiferal species are indicative of an intertidal to a subtidal environment in the palaeo-bay during the early to mid-Holocene. Abrupt coarsening of sediment grain size and a corresponding increase in the abundance of foraminiferal species of inner and middle shelf environments occurred at ca. 8.8 cal. kyr BP and 7.6 cal. kyr BP, reflecting two major events of strengthened marine transgression that correspond to the rapid global sea-level rise events of Meltwater pulses (MWPs) 1C and 1D, respectively. A marked increase in the relative abundance of Ammonia annectens and Ammonia compressiuscula during ca. 7.5–7.1 cal. kyr BP further indicates frequent storm surges at that time. Between the two rapid transgression events, aggradation of tidal flats prevailed after ca. 8.0 cal. kyr BP, which provided a suitable setting for Neolithic settlements, as indicated by the recently discovered Jingtoushan site. However, the transgression sequence associated with the latter, the MWP-1D event, caused a regional cultural interruption at ca. 7.6 cal. kyr BP. Infilling and coastal marsh development in the palaeo-Ningbo Bay occurred progressively after ca. 7.0 cal. kyr BP and are associated with the emergence of the Hemudu culture.
Nasal airflow patterns in a patient with septal deviation and comparison with a healthy nasal cavity using computational fluid dynamics
Authors: Corda John Valerian , Shenoy B. Satish , Lewis Leslie , K. Prakashini , Khader S. M. Abdul , Ahmad Kamarul Arifin , Zuber Mohammad
Published: November 2022

Background and objective: Causes for nasal airway obstruction (NAO) are many but septum deviation is the most prevalent etiology. A deviated septum affects the airflow dynamics in the human nasal cavity, which in turn affects the physiological functions of the nasal cavity like heating, humidification, and filtration capabilities. The present study investigates and compares the airflow patterns in a healthy nasal cavity to a septal deviated nasal cavity.

Methods: Two nasal airway models are considered and compared in this study. One with a septal deviation and the second with a healthy patent nasal cavity. Airflow analysis is carried out by developing the CT scans into 3D models using Materialise MIMICS (Materialise, Ann Arbor, MI), and then using the FLUENT solver of ANSYS 2020R2. The simulations are carried out for airflows ranging in laminar and turbulent flows using the SST k-ω turbulence model. Polyhedral meshes are used and the mesh check using Grid Convergence Index studies is adopted.

Results: The pressure and velocity profiles are assessed for a wide range of mass flow rates. The results indicate a turbulent flow pattern for mass flow rates over 15 LPM. The velocity profiles show aberrated flow profiles in a septal deviated nasal cavity where the peak velocity is observed at the mid-nasal region rather than the nasal valve region. There was a 38% to 55% higher nasal resistance in the septal deviated nasal cavity as compared to a normal and healthy nasal cavity. The pressure drop in the septal deviated nasal cavity is higher by 60%–120% when compared to a healthy nasal cavity.

Conclusion: The septal deviated nasal cavity greatly affects the nasal airflow distribution resulting in higher velocities in the mid-nasal region, increased pressure drop and higher nasal resistance. Hence the NAO with septal deviation has to be rectified with proper surgical procedures.
Nordic survey on assessment and treatment of fluid overload in intensive care
Authors: Zeuthen Emilie , Wichmann Sine , Schønemann-Lund Martin , Järvisalo Mikko J. , Rubenson-Wahlin Rebecka , Sigurðsson Martin I. , Holen Erling , Bestle Morten H.
Published: November 2022

Introduction

Fluid overload in patients in the intensive care unit (ICU) is associated with higher mortality. There are few randomized controlled trials to guide physicians in treating patients with fluid overload in the ICU, and no guidelines exist. We aimed to elucidate how ICU physicians from Nordic countries define, assess, and treat fluid overload in the ICU.

Materials and methods

We developed an online questionnaire with 18 questions. The questions were pre-tested and revised by specialists in intensive care medicine. Through a network of national coordinators. The survey was distributed to a wide range of Nordic ICU physicians. The distribution started on January 5th, 2022 and ended on May 6th, 2022.

Results

We received a total of 1,066 responses from Denmark, Norway, Finland, Sweden, and Iceland. When assessing fluid status, respondents applied clinical parameters such as clinical examination findings, cumulative fluid balance, body weight, and urine output more frequently than cardiac/lung ultrasound, radiological appearances, and cardiac output monitoring. A large proportion of the respondents agreed that a 5% increase or more in body weight from baseline supported the diagnosis of fluid overload. The preferred de-resuscitation strategy was diuretics (91%), followed by minimization of maintenance (76%) and resuscitation fluids (71%). The majority declared that despite mild hypotension, mild hypernatremia, and ongoing vasopressor, they would not withhold treatment of fluid overload and would continue diuretics. The respondents were divided when it came to treating fluid overload with loop diuretics in patients receiving noradrenaline. Around 1% would not administer noradrenaline and diuretics simultaneously and 35% did not have a fixed upper limit for the dosage. The remaining respondents 63% reported different upper limits of noradrenaline infusion (0.05–0.50 mcg/kg/min) when administering loop diuretics.

Conclusion

Self-reported practices among Nordic ICU physicians when assessing, diagnosing, and treating fluid overload reveals variability in the practice. A 5% increase in body weight was considered a minimum to support the diagnosis of fluid overload. Clinical examination findings were preferred for assessing, diagnosing and treating fluid overload, and diuretics were the preferred treatment modality.
Global occurrence of the bacteria with capability for extracellular reduction of iodate
Authors: Guo Jinzhi , Jiang Jie , Peng Zhaofeng , Zhong Yuhong , Jiang Yongguang , Jiang Zhou , Hu Yidan , Dong Yiran , Shi Liang
Published: November 2022

The γ-proteobacterium Shewanella oneidensis MR-1 reduces iodate to iodide extracellularly. Both dmsEFAB and mtrCAB gene clusters are involved in extracellular reduction of iodate by S. oneidensis MR-1. DmsEFAB reduces iodate to hypoiodous acid and hydrogen peroxide (H2O2). Subsequently, H2O2 is reduced by MtrCAB to facilitate DmsEFAB-mediated extracellular reduction of iodate. To investigate the distribution of bacteria with the capability for extracellular reduction of iodate, bacterial genomes were systematically searched for both dmsEFAB and mtrCAB gene clusters. The dmsEFAB and mtrCAB gene clusters were found in three Ferrimonas and 26 Shewanella species. Coexistence of both dmsEFAB and mtrCAB gene clusters in these bacteria suggests their potentials for extracellular reduction of iodate. Further analyses demonstrated that these bacteria were isolated from a variety of ecosystems, including the lakes, rivers, and subsurface rocks in East and Southeast Asia, North Africa, and North America. Importantly, most of the bacteria with both dmsEFAB and mtrCAB gene clusters were found in different marine environments, which ranged from the Arctic Ocean to Antarctic coastal marine environments as well as from the Atlantic Ocean to the Indian and Pacific Oceans. Widespread distribution of the bacteria with capability for extracellular reduction of iodate around the world suggests their significant importance in global biogeochemical cycling of iodine. The genetic organization of dmsEFAB and mtrCAB gene clusters also varied substantially. The identified mtrCAB gene clusters often contained additional genes for multiheme c-type cytochromes. The numbers of dmsEFAB gene cluster detected in a given bacterial genome ranged from one to six. In latter, duplications of dmsEFAB gene clusters occurred. These results suggest different paths for these bacteria to acquire their capability for extracellular reduction of iodate.
Quality assessment of virus-like particle: A new transmission electron microscopy approach
Authors: De Sá Magalhães Salomé , De Santis Emiliana , Hussein-Gore Saba , Colomb-Delsuc Mathieu , Keshavarz-Moore Eli
Published: November 2022

Transmission electron microscopy (TEM) is a gold standard analytical method for nanoparticle characterization and is playing a valuable role in virus-like particle (VLP) characterization extending to other biological entities such as viral vectors. A dedicated TEM facility is a challenge to both small and medium-sized enterprises (SMEs) and companies operating in low-and-middle income countries (LMICs) due to high start-up and running costs. A low-voltage TEM solution with assisted image acquisition and analysis such as the MiniTEM system, coupled with Vironova Imaging and Analysis Software (VIAS) could provide an affordable and practical alternative. The MiniTEM system has a small footprint and software that enables semi-automated data collection and image analysis workflows using built-in deep learning methods (convolutional neural networks) for automation in analysis, increasing speed of information processing and enabling scaling to larger datasets. In this perspective we outline the potential and challenges in the use of TEM as mainstream analytical tool in manufacturing settings. We highlight the rationale and preliminary findings from our proof-of-concept study aiming to develop a method to assess critical quality attributes (CQAs) of VLPs and facilitate adoption of TEM in manufacturing settings. In our study we explored all the steps, from sample preparation to data collection and analysis using synthetic VLPs as model systems. The applicability of the method in product development was verified at pilot-scale during the technology transfer of dengue VLPs development from a university setting to an LMIC- based vaccine manufacturing company, demonstrating the applicability of this analytical technique to VLP vaccine characterization.
Neuronal and non-neuronal scaling across brain regions within an intercross of domestic and wild chickens
Authors: Cunha Felipe , Stingo-Hirmas Diego , Cardoso Rita France , Wright Dominic , Henriksen Rie
Published: November 2022

The allometric scaling of the brain size and neuron number across species has been extensively studied in recent years. With the exception of primates, parrots, and songbirds, larger brains have more neurons but relatively lower neuronal densities than smaller brains. Conversely, when considering within-population variability, it has been shown that mice with larger brains do not necessarily have more neurons but rather more neurons in the brain reflect higher neuronal density. To what extent this intraspecific allometric scaling pattern of the brain applies to individuals from other species remains to be explored. Here, we investigate the allometric relationships among the sizes of the body, brain, telencephalon, cerebellum, and optic tectum, and the numbers of neurons and non-neuronal cells of the telencephalon, cerebellum, and optic tectum across 66 individuals originated from an intercross between wild and domestic chickens. Our intercross of chickens generates a population with high variation in brain size, making it an excellent model to determine the allometric scaling of the brain within population. Our results show that larger chickens have larger brains with moderately more neurons and non-neuronal cells. Yet, absolute number of neurons and non-neuronal cells correlated strongly and positively with the density of neurons and non-neuronal cells, respectively. As previously shown in mice, this scaling pattern is in stark contrast with what has been found across different species. Our findings suggest that neuronal scaling rules across species are not a simple extension of the neuronal scaling rules that apply within a species, with important implications for the evolutionary developmental origins of brain diversity.
Bearing fault diagnosis based on particle swarm optimization fusion convolutional neural network
Authors: Liu Xian , Wu Ruiqi , Wang Rugang , Zhou Feng , Chen Zhaofeng , Guo Naihong
Published: November 2022

Bearings are the most basic and important mechanical parts. The stable and safe operation of the equipment requires bearing fault diagnosis in advance. So, bearing fault diagnosis is an important technology. However, the feature extraction quality of the traditional convolutional neural network bearing fault diagnosis is not high and the recognition accuracy will decline under different working conditions. In response to these questions, a bearing fault model based on particle swarm optimization (PSO) fusion convolution neural network is proposed in this paper. The model first adaptively adjusts the hyperparameters of the model through PSO, then introduces residual connections to prevent the gradient from disappearing, uses global average pooling to replace the fully connected layer to reduce the training parameters of the model, and finally adds a dropout layer to prevent network overfitting. The experimental results show that the model is under four conditions, two of which can achieve 100% recognition, and the other two can also achieve more than 98% accuracy. And compared with the traditional diagnosis method, the model has higher accuracy under variable working conditions. This research has important research significance and economic value in the field of the intelligent machinery industry.
Igneous: Distributed dense 3D segmentation meshing, neuron skeletonization, and hierarchical downsampling
Authors: Silversmith William , Zlateski Aleksandar , Bae J. Alexander , Tartavull Ignacio , Kemnitz Nico , Wu Jingpeng , Seung H. Sebastian
Published: November 2022

Three-dimensional electron microscopy images of brain tissue and their dense segmentations are now petascale and growing. These volumes require the mass production of dense segmentation-derived neuron skeletons, multi-resolution meshes, image hierarchies (for both modalities) for visualization and analysis, and tools to manage the large amount of data. However, open tools for large-scale meshing, skeletonization, and data management have been missing. Igneous is a Python-based distributed computing framework that enables economical meshing, skeletonization, image hierarchy creation, and data management using cloud or cluster computing that has been proven to scale horizontally. We sketch Igneous's computing framework, show how to use it, and characterize its performance and data storage.
Memory decline in young stroke survivors during a 9-year follow-up: A cohort study
Authors: Laari Siiri , Turunen Katri , Kauranen Tatu , Mustanoja Satu , Lahti-Pulkkinen Marius , Tatlisumak Turgut , Poutiainen Erja
Published: November 2022

Introduction

A decade after stroke, young stroke survivors continue to suffer from cognitive impairment. However, it is not known whether this long-term cognitive outcome is caused in part by further cognitive decline or solely by incomplete recovery from the acute effects of ischemic stroke. We studied changes in three cognitive domains over a 9-year follow-up period after first-ever and only ischemic stroke.

Patients and methods

In this prospective, two-center cohort study, we recruited consecutive 18–65 year-old patients with acute stroke between 2007 and 2009, along with demographically matched stroke-free controls. We performed comprehensive neuropsychological assessments at 3 months, 2, and 9 years after stroke, and we also performed neurological examinations at the time of inclusion and at the 9-year follow-up. We assessed the associations among stroke, follow-up time and long-term cognitive outcomes using repeated-measures analysis of variance.

Results

The subjects comprised 85 patients who had had their first-ever and only ischemic stroke (mean age 53 years at inclusion), along with 31 stroke-free demographic controls. We compared the cognitive changes in patients to those in controls over a 9-year follow-up. After initial recovery between 3 months and 2 years after stroke, patients showed a decline in memory between 2 and 9 years after stroke compared to controls within the same time interval (immediate recall p < 0.001; delayed recall p < 0.001; list learning p < 0.001). Other than memory, we found no difference in cognitive changes between poststroke patients and controls.

Discussion

Our main finding was memory decline over a decade in young first-ever stroke patients with no further stroke or neurodegenerative disease. Our study extends the previous results of further memory decline in elderly stroke survivors to young stroke survivors.

Conclusion

Young stroke survivors might be at risk of memory decline over the decade following the stroke.