bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterisation of the urinary microbiome of a frog, and the effect of antibiotics on bacterial abundance and sperm viability during refrigerated storage
Authors: Anastas Zara M. , Byrne Phillip G. , Silla Aimee J.
Published: March 2024

Reproductive technologies are increasingly being adopted to improve the conservation management of threatened species. The storage and transport of sperm is a vital aspect of the practical implementation of reproductive technologies, however, bacterial contamination during the storage and transport of sperm samples presents a biosecurity risk and can contribute to a reduction in sperm longevity during storage. The present study: 1) characterised the urinary microbiome (bacterial species composition and abundance) using culture-independent 16S rRNA sequencing; 2) quantified the effect of various doses of gentamicin and streptomycin-penicillin on bacterial abundance (colony-forming units; CFUs) and; 3) quantified the effect of antibiotic supplementation on the sperm viability (proportion live/dead) of spermic urine during a 12-day cold-storage period, using the common eastern froglet, Crinia signifera. Overall, urine samples were found to host a diverse array of bacteria, dominated by the phyla Proteobacteria, Firmicutes, and Bacteroidetes. Bacterial abundance was significantly reduced in all antibiotic treatment groups compared to the control group. Antibiotic supplementation had no effect on sperm viability between day 0 and day 6 of storage, however both antibiotic treatments significantly improved sperm viability from days 9 to 12 of storage compared to the control group. Overall, the results of this study provide novel insight into the urinary microbiome, being the first to use a metagenomics approach to characterise the bacterial community present in the urine of an amphibian. Importantly, this study provides evidence that antibiotic supplementation with either gentamicin or streptomycin-penicillin, minimises bacterial proliferation and improves sperm viability during cold storage. These findings will contribute to the development of biosecurity protocols aimed at reducing the risk of disease transmission and cross-infection from unwanted bacteria and infectious agents in amphibian captive breeding programs.
Exploring blood lipids-immunity associations following HBV vaccination: evidence from a large cross-sectional study
Authors: Yang Qian , Li Benhua , Luan Tiankuo , Wang Xiaoyu , Duan Bixia , Wei Chengcheng , Chen Shi
Published: March 2024

Introduction

Serological responses following hepatitis B vaccination are crucial for preventing hepatitis B (HBV). However, the potential relationship between serum lipid levels and immunity from HBV vaccination remains poorly understood.

Methods

In this study, we conducted an analysis of the National Health and Nutrition Examination Survey (NHANES) data spanning from 2003 to 2016. Multivariable weighted logistic regression models, generalized linear analysis, stratified models, smooth curve fitting, segmentation effect analysis and sensitivity analysis were utilized to assess the relationships.

Results

After adjusting for relevant covariates, we observed that low levels of high-density lipoprotein cholesterol (HDL) were independently linked to a significantly lower seroprotective rate. Compared to HDL levels of ≥ 60 mg/dL, the odds ratios (ORs) for individuals with borderline levels (40-59 mg/dL for men, 50-59 mg/dL for women) and low levels (< 40 mg/dL for men, < 50 mg/dL for women) were 0.83 (95% CI 0.69-0.99) and 0.65 (95% CI 0.56-0.78), respectively. This association was particularly pronounced in individuals aged 40 or older. Conversely, higher levels of the triglyceride to HDL (TG/HDL) ratio (OR, 0.90; 95% CI, 0.84-0.98), total cholesterol to HDL (Chol/HDL) ratio (OR, 0.77; 95% CI, 0.64-0.92), and low-density lipoprotein to HDL (LDL/HDL) ratio (OR, 0.85; 95% CI, 0.76-0.96) were associated with a decreased likelihood of seroprotection.

Conclusion

This study suggests that lipid levels may play a role in modulating the immune response following HBV vaccination.
Mendelian randomization supports genetic liability to hospitalization for COVID-19 as a risk factor of pre-eclampsia
Authors: Wu Weizhen , Zhang Junning , Qiao Yizhuo , Ren Yuehan , Rao Xuezhi , Xu Zhijie , Liu Baoxing
Published: March 2024

Background

Pre-eclampsia and eclampsia are among the major threats to pregnant women and fetuses, but they can be mitigated by prevention and early screening. Existing observational research presents conflicting evidence regarding the causal effects of coronavirus disease 2019 (COVID-19) on pre-eclampsia risk. Through Mendelian randomization (MR), this study aims to investigate the causal effect of three COVID-19 severity phenotypes on the risk of pre-eclampsia and eclampsia to provide more rigorous evidence.

Methods

Two-sample MR was utilized to examine causal effects. Summary-level data from genome-wide association studies (GWAS) of individuals of European ancestry were acquired from the GWAS catalog and FinnGen databases. Single-nucleotide polymorphisms associated with COVID-19 traits at p < 5 × −8 were obtained and pruned for linkage disequilibrium to generate instrumental variables for COVID-19. Inverse variance weighted estimates were used as the primary MR results, with weighted median and MR-Egger as auxiliary analyses. The robustness of the MR findings was also evaluated through sensitivity analyses. Bonferroni correction was applied to primary results, with a p < 0.0083 considered significant evidence and a p within 0.083–0.05 considered suggestive evidence.

Results

Critical ill COVID-19 [defined as hospitalization for COVID-19 with either a death outcome or respiratory support, OR (95% CI): 1.17 (1.03–1.33), p = 0.020] and hospitalized COVID-19 [defined as hospitalization for COVID-19, OR (95% CI): 1.10 (1.01–1.19), p = 0.026] demonstrated suggestive causal effects on pre-eclampsia, while general severe acute respiratory syndrome coronavirus 2 infection did not exhibit a significant causal effect on pre-eclampsia. None of the three COVID-19 severity phenotypes exhibited a significant causal effect on eclampsia.

Conclusions

Our investigation demonstrates a suggestive causal effect of genetic susceptibility to critical ill COVID-19 and hospitalized COVID-19 on pre-eclampsia. The COVID-19 severity exhibited a suggestive positive dose–response relationship with the risk of pre-eclampsia. Augmented attention should be paid to pregnant women hospitalized for COVID-19, especially those needing respiratory support.
Case report of belt electrode-skeletal muscle electrical stimulation for acute heart failure with severe obesity: a novel therapeutic option for acute phase rehabilitation
Authors: Mochizuki Yuto , Jimba Takahiro , Yasukawa Syota , Katsura Aritomo , Fukuda Akira , Ando Jiro
Published: March 2024

Background

Belt electrode skeletal muscle electrical stimulation (B-SES) is an emerging therapy anticipated to yield more favorable outcomes than conventional neuromuscular electrical stimulation (NMES), owing to its larger stimulation area. However, information on its efficacy and safety in patients with heart failure remains limited.

Case presentation

A 43-year-old man with a body mass index of 41 kg/m2 was admitted to our hospital for acute heart failure due to dilated cardiomyopathy. The patient required prolonged catecholamine support owing to poor cardiac function, and heart transplantation was considered. We initiated a mobilization program, but the patient's mobility was highly limited due to severe obesity and symptomatic orthostatic hypotension. B-SES was introduced to accomplish weight loss and early ambulation. We applied an intensive monitoring program for safe use and modulated the intensity of B-SES according to physical function. During the B-SES program, the patient's body weight decreased from 89.6 kg to 78.6 kg. Sequential evaluations of body composition and skeletal muscle ultrasonography revealed improved muscle mass, quality, and physical function. Furthermore, we explored the workload of B-SES using expiratory gas analysis. No adverse events were observed during B-SES.

Discussion

We successfully used B-SES to improve muscle function and morbidity in the treatment of acute heart failure. B-SES could be an option for patients with heart failure who have limited mobility and obesity.
Experiments on the flow over a hill covered by a canopy in stably stratified conditions
Authors: Finnigan John J. , Harman Ian N. , Hughes Dale E.
Published: March 2024

It has long been suspected that thermo-topographic flows, especially gravity currents, within vegetation canopies on complex terrain are one of the main reasons behind the failure to reconcile micrometeorological and biometric estimates of canopy-atmosphere exchange at many sites. However, the physical mechanisms governing the initiation and the scaling of these flows remain poorly understood. Here we present the results of a novel wind tunnel study that looks in detail at the flow within and above an open canopy in stably stratified conditions and investigates the physical mechanisms responsible for gravity currents within canopies. The wind tunnel simulations demonstrate that gravity currents are established through a complex balance of competing forces on the flow within the canopy. Three forcing terms act on the flow in the canopy as it passes over the hill. First is the hydrodynamic pressure gradient associated with the boundary layer flow aloft; second, a hydrostatic pressure gradient associated with the displacement of temperature and density surfaces by the hill, and finally a thermal wind term, where a streamwise pressure gradient is caused by changes in the depth of the temperature perturbations to the flow. The net balance of these forces is opposed by the canopy drag. Gravity currents, however, do not appear unless the turbulence, which supports the transport of momentum into the canopy, is also reduced. This suppression occurs preferentially deep within the canopy due to a Richardson number cut-off effect, which is directly linked to the different transport mechanisms of heat and momentum across the boundary layers on the canopy elements. The gravity current first appears at the ground surface, despite cooling profiles that are concentrated in the upper canopy. Once initiated, a gravity current can propagate substantial distances away from the triggering topography, driven by the thermal wind term. If shown to be robust these results have widespread implications for the micrometeorology, atmospheric boundary layer and numerical weather prediction communities.
The social innovation profile in students as a transformation strategy: structural equation modeling
Authors: Glasserman-Morales Leonardo David , Alcantar-Nieblas Carolina , Nava-Lara Sergio
Published: March 2024

The development of social entrepreneurship competencies in university students favors the generation of proposals for solutions to different social problems, thus promoting a positive social impact capable of transforming people’s living conditions. This study aims to analyze the relationship between the dimensions of social entrepreneurship competence: entrepreneurial management, social value, leadership, effective communication and social innovation. A total of 408 higher education students from 13 countries and six different disciplinary areas participated in the study, ranging in age from 18 to 58 years (M = 22.4, SD = 6.0). The social entrepreneurship instrument was used, which is composed of 28 items grouped into five dimensions. A structural equation model was calculated. The findings indicate that entrepreneurial management, social value, and leadership are directly and positively related to personal competencies and social innovation. These results prove the importance of social entrepreneurship training in the development of social innovation in students, it is important that educational institutions in general carry out a review of their curricula and programs that take into account the development of social innovation competence as a factor that can enhance social change.
Can drones be a solution for defibrillation and blood transfusions? A review on the impact of new technologies in emergency healthcare
Authors: Akman Canan , Suzer Neslihan Ergun , Karcioglu Ozgur
Published: March 2024

Life-threatening arrhythmias, shock and airway compromise represent the most crucial situations to treat in the daily routine of acute medicine. Rapid access to automated external defibrillators (AEDs) and other necessary equipment increases survival rates significantly. The unmanned aerial vehicles (UAV) appear to revolutionize prehospital medicine enabling advanced health care delivery to those in austere environments and difficult regions for both defibrillators and blood products (BP). Although there are still many factors to consider, drone networks show potential to greatly reduce lifesaving equipment travel times for those with cardiac arrest (CA). More research should be performed to fill the gaps in routine practice of operating drones in different clinical scenarios, and geographical variations. As far as delivery of BP via drones, key benefits are minimized risk to human life, cost, speed of delivery and ability to cover areas beyond those of conventional planes. Challenges can be airspace management of BP, decisions on appropriate level of care to deliver during transit and user acceptability. Appropriate integration of drones to ambulances and emergency medical services facilitates efforts to improve healthcare, particularly in difficult and underserved regions. In brief, indications of drone use should be individualized to deliver vital equipment and care to the victim in emergency need, while the effectivity of UAVs must be evaluated case by case basis. This article aims to review the current status of above-mentioned technology and pluses and minuses of UAVs used worldwide, along with future projections.
Association of the metabolic score for insulin resistance with cardiovascular diseases, cardiovascular and all-cause mortality in Chinese hypertensive population
Authors: Zhang Liting , Yu Chao , Wang Tao , Zhou Wei , Bao Huihui , Cheng Xiaoshu
Published: March 2024

Importance

Little is known about the relationship between the metabolic score for insulin resistance (METS-IR) and the prognosis of hypertensive patients in China.

Objective

To investigate the association between the novel non–insulin‐based METS-IR index and the cardiovascular composite endpoints and all-cause mortality in Chinese hypertensive participants.

Design, setting, and participants

This cohort study used data from the China H-Type Hypertension Project, a long-term prospective cohort consisting of 14234 hypertensive patients in southern China, with a baseline from March to August 2018. The median follow-up period for participants was 3.94 years, as of 2022. The data analysis period is from July 2023 to September 2023.

Exposures

METS-IR index of participants in the Chinese H-type hypertension project. The calculation formula for METS-IR is (Ln (2 × FPG) +TG) × BMI/Ln (HDL-C).

Main outcomes and measures

Cardiovascular events and cardiovascular, all-cause mortality were identified by linking the cohort database with the health care system through October, 2023.

Results

A total of 14220 participants were included in this study. The prevalence rates of cardiovascular disease (CVD), cardiovascular death, and all-cause death were 2.59% (369/14220), 2.79% (397/14220), and 5.66% (805/14220), respectively. After adjusting for confounding factors in the multivariate logistic regression analysis models, the METS-IR index was significantly positively correlated with CVD, and cardiovascular, all-cause mortality, whether as a categorical or continuous variable. Layered analysis showed that the METS-IR index of hypertensive participants in different subgroups was positively correlated with the endpoint event.

Conclusions and relevance

This large, prospective cohort study demonstrated that the METS-IR index, a new IR evaluation index, were independently associated with a higher risk of the cardiovascular composite endpoint and all-cause mortality among Chinese hypertensive population. Importantly, our finding provides an independent indicator for evaluating the prognosis of hypertensive patients.
Expression and clinical value of CXCR4 in high grade gastroenteropancreatic neuroendocrine neoplasms
Authors: Pang Chaoyu , Li Yongzheng , Shi Ming , Fan Zhiyao , Gao Xin , Meng Yufan , Liu Shujie , Gao Changhao , Su Peng , Wang Xiao , Zhan Hanxiang
Published: March 2024

Background

CXC chemokine receptor 4 (CXCR4) is associated with the progression and metastasis of numerous malignant tumors. However, its relationship with Gastroenteropancreatic Neuroendocrine Neoplasms Grade 3 (GEP-NENs G3) is unclear. The aim of this study was to characterize the expression of CXCR4 in GEP-NENS and to explore the clinical and prognostic value of CXCR4.

Methods

This study retrospectively collected clinical and pathological data from patients with GEP-NENs who receiving surgery in Qilu Hospital of Shandong University from January 2013 to April 2021, and obtained the overall survival of the patients based on follow-up. Immunohistochemistry (IHC) was performed on pathological paraffin sections to observe CXCR4 staining. Groups were made according to pathological findings. Kaplan-Meier (K-M) curve was used to evaluate prognosis. SPSS 26.0 was used for statistical analysis.

Results

100 GEP-NENs G3 patients were enrolled in this study. There was a significant difference in primary sites (P=0.002), Ki-67 index (P<0.001), and Carcinoembryonic Antigen (CEA) elevation (P=0.008) between neuroendocrine tumor (NET) G3 and neuroendocrine carcinoma (NEC). CXCR4 was highly expressed only in tumors, low or no expressed in adjacent tissues (P<0.001). The expression level of CXCR4 in NEC was significantly higher than that in NET G3 (P=0.038). The K-M curves showed that there was no significant difference in overall survival between patients with high CXCR4 expression and patients with low CXCR4 expression, either in GEP-NEN G3 or NEC (P=0.920, P=0.842. respectively).

Conclusion

Differential expression of CXCR4 was found between tumor and adjacent tissues and between NET G3 and NEC. Our results demonstrated that CXCR4 can be served as a new IHC diagnostic indicator in the diagnosis and differential diagnosis of GEP-NENs G3. Further studies with multi-center, large sample size and longer follow-up are needed to confirm the correlation between CXCR4 expression level and prognosis.
Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease: friend or foe
Authors: Chondrogianni Maria Eleni , Kyrou Ioannis , Androutsakos Theodoros , Flessa Christina-Maria , Menenakos Evangelos , Chatha Kamaljit Kaur , Aranan Yekaterina , Papavassiliou Athanasios G. , Kassi Eva , Randeva Harpal S.
Published: March 2024

Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into the most common chronic liver disease globally, affecting 17-38% of the general population and 50-75% of patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum of chronic liver diseases, ranging from simple steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis and cirrhosis with liver failure or/and hepatocellular carcinoma. Due to its increasing prevalence and associated morbidity and mortality, the disease-related and broader socioeconomic burden of NAFLD is substantial. Of note, currently there is no globally approved pharmacotherapy for NAFLD. Similar to NAFLD, osteoporosis constitutes also a silent disease, until an osteoporotic fracture occurs, which poses a markedly significant disease and socioeconomic burden. Increasing emerging data have recently highlighted links between NAFLD and osteoporosis, linking the pathogenesis of NAFLD with the process of bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence is needed towards discovering potential causative links. Since these two chronic diseases frequently co-exist, there are data suggesting that anti-osteoporosis treatments may affect NAFLD progression by impacting on its pathogenetic mechanisms. In the present review, we present on overview of the current understanding of the liver-bone cross talk and summarize the experimental and clinical evidence correlating NAFLD and osteoporosis, focusing on the possible effects of anti-osteoporotic drugs on NAFLD.
Deep learning-based dynamic forecasting method and application for ultra-deep fractured reservoir production
Authors: Deng Ziyan , Zhou Dongsheng , Kang Zhijiang , Dong Hezheng
Published: March 2024

Addressing the complex challenges in dynamic production forecasting for the deep-ultra-deep fractured carbonate reservoirs in the Tarim Basin’s Tahe Oilfield, characterized by numerous influencing factors, strong temporal variations, high non-linearity, and prediction difficulties, We proposes a prediction method based on Gated Recurrent Unit networks (GRU). Initially, the production data and influencing factors are subjected to dimensionality reduction using Pearson correlation coefficient and principal component analysis methods to obtain multi-attribute time series data. Subsequently, deep learning modeling of time series data is conducted using Gated Recurrent Unit networks. The model is then optimized using the Optuna algorithm and applied to the dynamic production forecasting of the deep-ultra-deep fractured carbonate reservoirs in the Tahe Oilfield. The results demonstrate that the Gated Recurrent Unit network model optimized by Optuna excels in the dynamic production forecasting of the Tahe fractured carbonate reservoirs. Compared with the traditional method, the mean absolute error (MAE), the root mean square error (MSE) and the mean absolute percentage error (MAPE) are reduced by 0.04, 0.1 and 1.1, respectively. This method proves to be more adaptable to the production forecasting challenges of deep fractured reservoirs, providing an effective means to enhance model performance. It holds significant practical value and importance in guiding the development of fractured reservoirs.
Neurodevelopmental disorders as a risk factor for temporomandibular disorder: evidence from Mendelian randomization studies
Authors: Wu Xueqiang , Li Zefang , Cui Yiping , Yan Zhaojun , Lu Tingting , Cui Song
Published: March 2024

Objective: This study aims to clarify the incidence rate of temporomandibular joint disease in patients with mental disorders.

Methods: Data extracted from the Psychiatric Genomics Consortium and FinnGen databases employed the Mendelian Randomization (MR) method to assess the associations of three neurodevelopmental disorders (NDDs)—Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette’s Disorder (TD)—as exposure factors with Temporomandibular Disorder (TMD). The analysis used a two-sample MR design, employing the Inverse Variance Weighted (IVW) method to evaluate the relationships between these disorders and Temporomandibular Disorder. Sensitivity analysis and heterogeneity assessments were conducted. Potential confounding factors like low birth weight, childhood obesity, and body mass index were controlled for.

Results: The study found that ADHD significantly increased the risks for TMD (OR = 1.2342, 95%CI (1.1448–1.3307), p < 0.00001), TMD (including avohilmo) (OR = 1.1244, 95%CI (1.0643–1.1880), p = 0.00003), TMD-related pain (OR = 1.1590, 95%CI (1.0964–1.2252), p < 0.00001), and TMD-related muscular pain associated with fibromyalgia (OR = 1.1815, 95%CI (1.1133–1.2538), p < 0.00001), while other disorders did not show significant causal relationships.

Conclusion: This study reveals the elevated risk of various TMD aspects due to ADHD. Furthermore, we discuss the link between low vitamin D levels ADHD and TMD. Future research should address these limitations and delve further into the complex interactions between ADHD, ASD, TD, and TMD.
GPR41 and GPR43 regulate CD8+ T cell priming during herpes simplex virus type 1 infection
Authors: Lee Ariane Renita , Wilson Kayla Roberta , Clarke Michele , Engel Sven , Tscharke David C. , Gebhardt Thomas , Bedoui Sammy , Bachem Annabell
Published: March 2024

Naïve CD8+ T cells need to undergo a complex and coordinated differentiation program to gain the capacity to control virus infections. This not only involves the acquisition of effector functions, but also regulates the development of a subset of effector CD8+ T cells into long-lived and protective memory cells. Microbiota-derived metabolites have recently gained interest for their influence on T cells, but much remains unclear about their role in CD8+ T cell differentiation. In this study, we investigated the role of the G protein-coupled receptors (GPR)41 and GPR43 that can bind microbiota-derived short chain fatty acids (SCFAs) in CD8+ T cell priming following epicutaneous herpes simplex virus type 1 (HSV-1) infection. We found that HSV-specific CD8+ T cells in GPR41/43-deficient mice were impaired in the antigen-elicited production of interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), granzyme B and perforin, and failed to differentiate effectively into memory precursors. The defect in controlling HSV-1 at the site of infection could be restored when GPR41 and GPR43 were expressed exclusively by HSV-specific CD8+ T cells. Our findings therefore highlight roles for GPR41 and GPR43 in CD8+ T cell differentiation, emphasising the importance of metabolite sensing in fine-tuning anti-viral CD8+ T cell priming.
Progression of Notch signaling regulation of B cells under radiation exposure
Authors: Shu Xin , Wang Jie , Zeng Huihong , Shao Lijian
Published: March 2024

With the continuous development of nuclear technology, the radiation exposure caused by radiation therapy is a serious health hazard. It is of great significance to further develop effective radiation countermeasures. B cells easily succumb to irradiation exposure along with immunosuppressive response. The approach to ameliorate radiation-induced B cell damage is rarely studied, implying that the underlying mechanisms of B cell damage after exposure are eager to be revealed. Recent studies suggest that Notch signaling plays an important role in B cell-mediated immune response. Notch signaling is a critical regulator for B cells to maintain immune function. Although accumulating studies reported that Notch signaling contributes to the functionality of hematopoietic stem cells and T cells, its role in B cells is scarcely appreciated. Presently, we discussed the regulation of Notch signaling on B cells under radiation exposure to provide a scientific basis to prevent radiation-induced B cell damage.
Distinct functional neutrophil phenotypes in sepsis patients correlate with disease severity
Authors: Yang Qingliang , Langston Jordan C. , Prosniak Roman , Pettigrew Samantha , Zhao Huaqing , Perez Edwin , Edelmann Hannah , Mansoor Nadia , Merali Carmen , Merali Salim , Marchetti Nathaniel , Prabhakarpandian Balabhaskar , Kiani Mohammad F. , Kilpatrick Laurie E.
Published: March 2024

Purpose

Sepsis is a clinical syndrome defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis is a highly heterogeneous syndrome with distinct phenotypes that impact immune function and response to infection. To develop targeted therapeutics, immunophenotyping is needed to identify distinct functional phenotypes of immune cells. In this study, we utilized our Organ-on-Chip assay to categorize sepsis patients into distinct phenotypes using patient data, neutrophil functional analysis, and proteomics.

Methods

Following informed consent, neutrophils and plasma were isolated from sepsis patients in the Temple University Hospital ICU (n=45) and healthy control donors (n=7). Human lung microvascular endothelial cells (HLMVEC) were cultured in the Organ-on-Chip and treated with buffer or cytomix ((TNF/IL-1β/IFNγ). Neutrophil adhesion and migration across HLMVEC in the Organ-on-Chip were used to categorize functional neutrophil phenotypes. Quantitative label-free global proteomics was performed on neutrophils to identify differentially expressed proteins. Plasma levels of sepsis biomarkers and neutrophil extracellular traps (NETs) were determined by ELISA.

Results

We identified three functional phenotypes in critically ill ICU sepsis patients based on ex vivo neutrophil adhesion and migration patterns. The phenotypes were classified as: Hyperimmune characterized by enhanced neutrophil adhesion and migration, Hypoimmune that was unresponsive to stimulation, and Hybrid with increased adhesion but blunted migration. These functional phenotypes were associated with distinct proteomic signatures and differentiated sepsis patients by important clinical parameters related to disease severity. The Hyperimmune group demonstrated higher oxygen requirements, increased mechanical ventilation, and longer ICU length of stay compared to the Hypoimmune and Hybrid groups. Patients with the Hyperimmune neutrophil phenotype had significantly increased circulating neutrophils and elevated plasma levels NETs.

Conclusion

Neutrophils and NETs play a critical role in vascular barrier dysfunction in sepsis and elevated NETs may be a key biomarker identifying the Hyperimmune group. Our results establish significant associations between specific neutrophil functional phenotypes and disease severity and identify important functional parameters in sepsis pathophysiology that may provide a new approach to classify sepsis patients for specific therapeutic interventions.
Long noncoding RNAs and circular RNAs as potential diagnostic biomarkers of inflammatory bowel diseases: a systematic review and meta-analysis
Authors: Belete Melaku Ashagrie , Tadesse Selamyhun , Tilahun Mihret , Gedefie Alemu , Shibabaw Agumas , Mulatie Zewudu , Wudu Muluken Amare , Gebremichael Saba , Debash Habtu , Alebachew Mihreteab , Alemayehu Ermiyas
Published: March 2024

Introduction

Inflammatory bowel disease (IBD) poses a growing global burden, necessitating the discovery of reliable biomarkers for early diagnosis. The clinical significance of dysregulated expression of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in diagnosing IBD has not been well established. Thus, our study aimed to investigate the diagnostic value of lncRNAs and circRNAs for IBD based on currently available studies.

Methods

A comprehensive search was carried out in diverse electronic databases, such as PubMed, Embase, Scopus, Science Direct and Wiley Online Library to retrieve articles published until October 30, 2023. Stata 17.0 software was employed to determine pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the curve (AUC). Heterogeneity, subgroup analysis, and meta-regression were explored, and publication bias was assessed using Deeks’ funnel plot. Fagan’s nomogram and likelihood ratio scattergram were employed to evaluate the clinical validity.

Result

A total of 11 articles encompassing 21 studies which involved 1239 IBD patients and 985 healthy controls were investigated. The findings revealed lncRNAs exhibit high level of pooled sensitivity 0.94 (95% CI: 0.87-0.97) and specificity 0.99 (95% CI: 0.89-1.00), along with PLR, NLR, DOR, and AUC values of 64.25 (95% CI: 7.39-558.66), 0.06 (95% CI: 0.03-0.13), 1055.25 (95% CI: 70.61-15770.77), and 0.99 (95% CI: 0.97-0.99), respectively. Conversely, CircRNAs showed moderate accuracy in IBD diagnosis, with sensitivity of 0.68 (95% CI: 0.61-0.73), specificity of 0.73 (95% CI: 0.65-0.79), PLR of 2.47 (95% CI: 1.94-3.16), NLR of 0.45 (95% CI: 0.38-0.53), DOR of 5.54 (95% CI: 3.88-7.93), and AUC value of 0.75 (95% CI: 0.71-0.79). Moreover, findings from subgroup analysis depicted heightened diagnostic efficacy when employing lncRNA H19 and a large sample size (≥100), with notable efficacy in diagnosing both ulcerative colitis (UC) and Crohn’s disease (CD).

Conclusion

LncRNAs exhibit high diagnostic accuracy in distinguishing patients with IBD from healthy controls signifying their possible use as potential biomarkers, while circRNAs showed moderate diagnostic accuracy. Nevertheless, to validate our findings and confirm the clinical utility of lncRNAs and circRNAs in IBD diagnosis, a large pool of prospective and multi-center studies should be undertaken.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023491840.
Autoimmune and neuropsychiatric phenotypes in a Mecp2 transgenic mouse model on C57BL/6 background
Authors: Li Yaxi , Zhang Shu , Tang Chenling , Yang Bowen , Atrooz Fatin , Ren Zhifeng , Mohan Chandra , Salim Samina , Wu Tianfu
Published: March 2024

Introduction

Systemic Lupus Erythematosus (SLE) impacts the central nervous system (CNS), leading to severe neurological and psychiatric manifestations known as neuropsychiatric lupus (NPSLE). The complexity and heterogeneity of clinical presentations of NPSLE impede direct investigation of disease etiology in patients. The limitations of existing mouse models developed for NPSLE obstruct a comprehensive understanding of this disease. Hence, the identification of a robust mouse model of NPSLE is desirable.

Methods

C57BL/6 mice transgenic for human MeCP2 (B6.Mecp2Tg1) were phenotyped, including autoantibody profiling through antigen array, analysis of cellularity and activation of splenic immune cells through flow cytometry, and measurement of proteinuria. Behavioral tests were conducted to explore their neuropsychiatric functions. Immunofluorescence analyses were used to reveal altered neurogenesis and brain inflammation. Various signaling molecules implicated in lupus pathogenesis were examined using western blotting.

Results

B6.Mecp2Tg1 exhibits elevated proteinuria and an overall increase in autoantibodies, particularly in female B6.Mecp2Tg1 mice. An increase in CD3+CD4+ T cells in the transgenic mice was observed, along with activated germinal center cells and activated CD11b+F4/80+ macrophages. Moreover, the transgenic mice displayed reduced locomotor activity, heightened anxiety and depression, and impaired short-term memory. Immunofluorescence analysis revealed IgG deposition and immune cell infiltration in the kidneys and brains of transgenic mice, as well as altered neurogenesis, activated microglia, and compromised blood-brain barrier (BBB). Additionally, protein levels of various key signaling molecules were found to be differentially modulated upon MeCP2 overexpression, including GFAP, BDNF, Albumin, NCoR1, mTOR, and NLRP3.

Discussion

Collectively, this work demonstrates that B6.Mecp2Tg1 mice exhibit lupus-like phenotypes as well as robust CNS dysfunctions, suggesting its utility as a new animal model for NPSLE.
Identification of bacteria and fungi responsible for litter decomposition in desert steppes via combined DNA stable isotope probing
Authors: Ye He , Tu Nare , Wu Zhendan , He Shilong , Zhao Yu , Yue Mei , Hong Mei
Published: March 2024

Introduction

Soil microorganisms play crucial roles in determining the fate of litter in desert steppes because their activities constitute a major component of the global carbon (C) cycle. Human activities lead to increased ecosystem nitrogen (N) deposition, which has unpredictable impacts on soil microorganism diversity and functions. Nowadays, it is necessary to further study the succession of these microorganisms in the process of litter decomposition in desert steppe, and explore the effect of N deposition on this process. This issue is particularly important to resolve because it contributes to the broader understanding of nutrient cycling processes in desert steppes.

Methods

In this study, DNA stable isotope probing (DNA-SIP) was used to study changes in soil bacterial and fungal community composition and function during 8 weeks of culture of 13C-labeled litter in desert steppes.

Results

The results were as follows: (1) Actinomycetota, Pseudomonadota, and Ascomycota are the main microorganisms involved in litter decomposition in desert steppes; (2) N deposition (50 kg ha−1 year−1) significantly increased the relative abundance of some microorganisms involved in the decomposition process; and (3) N deposition likely promotes litter decomposition in desert steppes by increasing the abundances of N cycles bacteria (usually carrying GH family functional genes).

Discussion

These findings contribute to a deeper understanding of the C assimilation mechanisms associated with litter residue production, emphasizing the importance of extensive C utilization.
The C-terminal selenenylsulfide of extracellular/non-reduced thioredoxin reductase endows this protein with selectivity to small-molecule electrophilic reagents under oxidative conditions
Authors: Qin Huijun , Guo Chenchen , Chen Bozhen , Huang Hui , Tian Yaping , Zhong Liangwei
Published: March 2024

Mammalian cytosolic thioredoxin reductase (TrxR1) serves as an antioxidant protein by transferring electrons from NADPH to various substrates. The action of TrxR1 is achieved via reversible changes between NADPH-reduced and non-reduced forms, which involves C-terminal selenolthiol/selenenylsulfide exchanges. TrxR1 may be released into extracellular environment, where TrxR1 is present mainly in the non-reduced form with active-site disulfide and selenenylsulfide bonds. The relationships between extracellular TrxR1 and tumor metastasis or cellular signaling have been discovered, but there are few reports on small-molecule compounds in targeted the non-reduced form of TrxR1. Using eight types of small-molecule thiol-reactive reagents as electrophilic models, we report that the selenenylsulfide bond in the non-reduced form of TrxR1 functions as a selector for the thiol-reactive reagents at pH 7.5. The non-reduced form of TrxR1 is resistant to hydrogen peroxide/oxidized glutathione, but is sensitive to certain electrophilic reagents in different ways. With 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) and S-nitrosoglutathione (GSNO), the polarized selenenylsulfide bond breaks, and selenolate anion donates electron to the dynamic covalent bond in DTNB or GSNO, forming TNB-S-Se-TrxR1 complex or ON-Se-TrxR1 complex. The both complexes lose the ability to transfer electrons from NADPH to substrate. For diamide, the non-reduced TrxR1 actually prevents irreversible damage by this oxidant. This is consistent with the regained activity of TrxR1 through removal of diamide via dialysis. Diamide shows effective in the presence of human cytosolic thioredoxin (hTrx1), Cys residue(s) of which is/are preferentially affected by diamide to yield disulfide, hTrx1 dimer and the mixed disulfide between TrxR1-Cys497/Sec498 and hTrx1-Cys73. In human serum samples, the non-reduced form of TrxR1 exists as dithiothreitol-reducible polymer/complexes, which might protect the non-reduced TrxR1 from inactivation by certain electrophilic reagents under oxidative conditions, because cleavage of these disulfides can lead to regain the activity of TrxR1. The details of the selective response of the selenenylsulfide bond to electrophilic reagents may provide new information for designing novel small-molecule inhibitors (drugs) in targeted extracellular/non-reduced TrxR1.
Olfactory information processing viewed through mitral and tufted cell-specific channels
Authors: Hirata Tatsumi
Published: March 2024

Parallel processing is a fundamental strategy of sensory coding. Through this processing, unique and distinct features of sensations are computed and projected to the central targets. This review proposes that mitral and tufted cells, which are the second-order projection neurons in the olfactory bulb, contribute to parallel processing within the olfactory system. Based on anatomical and functional evidence, I discuss potential features that could be conveyed through the unique channel formed by these neurons.
Beta-informativeness-diffusion multilayer graph embedding for brain network analysis
Authors: Huang Yin , Li Ying , Yuan Yuting , Zhang Xingyu , Yan Wenjie , Li Ting , Niu Yan , Xu Mengzhou , Yan Ting , Li Xiaowen , Li Dandan , Xiang Jie , Wang Bin , Yan Tianyi
Published: March 2024

Brain network analysis provides essential insights into the diagnosis of brain disease. Integrating multiple neuroimaging modalities has been demonstrated to be more effective than using a single modality for brain network analysis. However, a majority of existing brain network analysis methods based on multiple modalities often overlook both complementary information and unique characteristics from various modalities. To tackle this issue, we propose the Beta-Informativeness-Diffusion Multilayer Graph Embedding (BID-MGE) method. The proposed method seamlessly integrates structural connectivity (SC) and functional connectivity (FC) to learn more comprehensive information for diagnosing neuropsychiatric disorders. Specifically, a novel beta distribution mapping function (beta mapping) is utilized to increase vital information and weaken insignificant connections. The refined information helps the diffusion process concentrate on crucial brain regions to capture more discriminative features. To maximize the preservation of the unique characteristics of each modality, we design an optimal scale multilayer brain network, the inter-layer connections of which depend on node informativeness. Then, a multilayer informativeness diffusion is proposed to capture complementary information and unique characteristics from various modalities and generate node representations by incorporating the features of each node with those of their connected nodes. Finally, the node representations are reconfigured using principal component analysis (PCA), and cosine distances are calculated with reference to multiple templates for statistical analysis and classification. We implement the proposed method for brain network analysis of neuropsychiatric disorders. The results indicate that our method effectively identifies crucial brain regions associated with diseases, providing valuable insights into the pathology of the disease, and surpasses other advanced methods in classification performance.
Provision of special diets to children in public nurseries and kindergartens in Kraków (Poland)
Authors: Piórecka Beata , Kozioł-Kozakowska Agnieszka , Holko Przemysław , Kowalska-Bobko Iwona , Kawalec Paweł
Published: March 2024

Background

A specialized diet could be due to an allergy or other medical needs and also religious or cultural reasons. This study aimed to assess the availability and provision of special diets in kindergartens and nurseries financed by the Municipality of Kraków.

Methods

This observational cross-sectional study was based on a diagnostic survey carried out using the Computer-Assisted Web Interview method and addressed to the managers of nurseries (n = 21) and kindergartens (n = 71) and, separately, to the parents of children attending these facilities (n = 1,096). Non-parametric tests were applied for an unadjusted comparison between children at nurseries and those at kindergartens.

Results

Children with particular dietary requirements received special diet meals in 95.2% of nurseries and 60.5% of kindergartens. The availability of special diets was associated with the type of facility (p = 0.001), the number of children who ate in the facility (p = 0.032), and the daily cost of meals served to children (p = 0.009). The cost of meals was higher in kindergartens that offered special diets vs. those that did not offer such diets (p < 0.001). According to parents, 96.4% of the total number of children ate meals served in the facilities. In nurseries, 16.1% of children were on a special diet (as per the doctor’s recommendations in 11.7% of cases and according to parents’ own choice in 4.4%). In kindergartens, a special diet was served to 12.7% of children (doctor’s recommendations, 8.5%; parents’ own choice, 4.2%). The most common reason for using a special diet was food allergy (8.2% of children in nurseries and 5.8% of children in kindergartens). It was reported more often by the parents of children attending nurseries than by the parents of children attending kindergartens (8.0% vs. 4.2%, p = 0.007). The requirement for a special diet was found to be associated with the age of children (p < 0.033) and the use of oral treatment for chronic disease (p < 0.001).

Conclusion

Providing special diets for children is better in nurseries than in kindergartens. Legal regulations are urgently needed to ensure equal access to adequate nutrition for all children with special dietary needs in childcare facilities.
Case report: Exceptional and durable response to Radium-223 and suspension of androgen deprivation therapy in a metastatic castration-resistant prostate cancer patient
Authors: Zacchi Francesca , Carles Joan , Gonzalez Macarena , Maldonado Xavier , Perez-Lopez Raquel , Semidey Maria Eugenia , Mateo Joaquin
Published: March 2024

Despite the development of new therapies in the last few years, metastatic prostate cancer (PCa) is still a lethal disease. Radium-223 (Ra-223) is approved for patients with advanced castration-resistant prostate cancer (CRPC) with bone metastases and no visceral disease. However, patients’ outcomes are heterogenous, and there is lack of validated predictive biomarkers of response, while biomarkers for early identification of patients who benefit from treatment are limited. This case report describes a remarkable and durable response to Ra-223 in a CRPC patient with bone metastases who had rapidly progressed to many previous therapies; this response is now lasting for 5 years even after having stopped backbone androgen deprivation therapy (ADT). Here, we present the clinical course of this exceptional response, as well as comprehensive genomic and histopathology analyses on sequential biopsies acquired before and after therapy. Additionally, we review current knowledge on predictive and response biomarkers to Ra-223 in metastatic prostate cancer.
Case report: Metastatic choriocarcinoma in the second trimester of a viable pregnancy with successful delivery and outcome after chemotherapy
Authors: Tian Yalin , Yu Jiayi , Dan Xin , Chen Tanglin , He Yalin
Published: March 2024

Metastatic choriocarcinoma during viable pregnancy is rare worldwide, and neonate survival following pregnancy termination in the second trimester is uncommon. Here, we report the successful delivery of a pregnancy by a patient with metastatic choriocarcinoma, who received three courses of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) chemotherapy in the second trimester. After multidisciplinary discussions, she was administered paclitaxel and carboplatin (TC) chemotherapy. Regular contractions occurred during her first paclitaxel infusion, and a healthy infant was delivered by cesarean section at 26+4 gestational weeks. Choriocarcinoma was not detected in the placenta. Following delivery of the pregnancy, the patient underwent total treatment comprising one cycle of TC, seven cycles of EMA-CO, and five courses of etoposide, cisplatin, methotrexate, and dactinomycin chemotherapy; her serum level of beta–human chorionic gonadotropin gradually fell after chemotherapy. Uterine and pulmonary metastases shrank, and no distant metastasis or recurrence were found until the eighth course of maintenance treatment with immunotherapy. The patient received periodic chemotherapy for recurrence at the time of publishing this case report. The child was disease-free 15+ months after delivery. Despite serious metastases and complications, metastatic choriocarcinoma diagnosed in the second trimester of pregnancy can be successfully treated with minimal delay by multidisciplinary medical and nursing management.