bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of HNF4alpha-cMyc interaction in liver regeneration after partial hepatectomy
Authors: Kotulkar Manasi , Paine-Cabrera Diego , Venneman Kaitlyn , Apte Udayan
Published: July 2024

Background

Hepatocyte nuclear factor 4 alpha (HNF4α) is the master regulator of hepatic differentiation. Recent studies have also revealed the role of HNF4α in hepatocyte proliferation via negatively regulating the expression of proto-mitogenic genes, including cMyc. Here, we aimed to study the interaction between HNF4α-cMyc during liver regeneration after partial hepatectomy (PHX).

Methods

Wild-type (WT), hepatocyte-specific knockout of HNF4α (HNF4α-KO), cMyc (cMyc-KO), and HNF4α-cMyc double knockout (DKO) mice were subjected to PHX to induce liver regeneration. Blood and liver tissue samples were collected at 0h, 24h, 48h, 7D, and 14D after PHX for further analysis.

Results

WT, HNF4α-KO, cMyc-KO and DKO mice regained liver weight by 14 days after PHX. The deletion of cMyc did not affect liver regeneration, which was similar to the WT mice. WT and cMyc-KO mice started regaining liver weight as early as 24 hours after PHX, with a peak proliferation response at 48 hours after PHX. HNF4α- KO and DKO showed a delayed response with liver weight increase by day 7 after PHX. The overall hepatocyte proliferation response by DKO mice following PHX was lower than that of other genotypes. Interestingly, the surviving HNF4α-KO and DKO mice showed re-expression of HNF4α at mRNA and protein levels on day 14 after PHX. This was accompanied by a significant increase in the expression of Krt19 and Epcam, hepatic progenitor cell markers, in the DKO mice on day 14 after PHX.

Conclusion

These data indicate that, in the absence of HNF4α, cMyc contributes to hepatocyte-driven proliferation to compensate for the lost tissue mass. Furthermore, in the absence of both HNF4α and cMyc, HPC-driven proliferation occurs to support liver regeneration.
The relationship between 25-hydroxy vitamin D and serum asprosin in patients with type 2 diabetes in the community
Authors: Cui Junfang , Wang Zhengqian , Yin Jianhong , Li Mina , Wu Qianqian , Liu Ming , Su Hong , Ren Huijuan , Xu Minggang , Yang Jing , Xu Linxin
Published: July 2024

Objectives

This study aimed to investigate the link between 25-hydroxy vitamin D and serum asprosin in individuals with type 2 diabetes within the community. The goal was to provide a foundation for clinical interventions.

Methods

Between November 2019 and July 2021, data from 463 patients with type 2 diabetes were consistently gathered at a community health service station in Southeast Shanxi Province. General information and laboratory metrics were compiled, including serum asprosin levels. The participants were categorized based on three serum asprosin quantiles, allowing for a comparison of various factors among the groups. The correlation between serum asprosin levels and other factors was analyzed. Employing a general linear model, the connection between 25-hydroxy vitamin D and serum asprosin levels was studied. Utilizing three quantiles of 25-hydroxy vitamin D, serum asprosin was treated as the dependent variable, while 25-hydroxy vitamin D served as the independent variable for linear regression analysis.

Results

As serum asprosin increased, there were gradual increments in age, disease duration, SBP, BMI, WC, creatinine, and SUA levels (P<0.05). Conversely, HbA1c, HDL-C, GFR, and 25-hydroxy vitamin D levels exhibited gradual declines (P<0.05). Age, 25-hydroxy vitamin D, SUA, creatinine, and LDL-C emerged as independent influencing factors for serum asprosin. Across the 1st to 3rd 25-hydroxy vitamin D quantiles, elevated 25-hydroxy vitamin D levels correlated with a gradual reduction in mean serum asprosin (P<0.05).

Conclusion

Serum asprosin levels demonstrate an inverse correlation with 25-hydroxy vitamin D levels in community-dwelling individuals with type 2 diabetes. Serum asprosin levels might independently contribute to 25-hydroxy vitamin D levels.
Association between oxidative balance score and diabetic kidney disease, low estimated glomerular filtration rate and albuminuria in type 2 diabetes mellitus patients: a cross-sectional study
Authors: Liu Cong , Yang Jiju , Li Hongdian , Deng Yuanyuan , He Pengfei , Zhang Jiao , Zhang Mianzhi
Published: July 2024

Objective

The oxidative balance score (OBS) is a comprehensive concept that includes 20 oxidative stressors and can be used to assess individual pro-oxidant versus antioxidant exposure, and the aim of the present study was to investigate the association between OBS and the risk of diabetic kidney disease (DKD), low estimated glomerular filtration rate (low-eGFR) and albuminuria in patients with diabetes mellitus (DM).

Methods

This cross-sectional study included nationally representative consecutive National Health and Nutrition Examination Survey DM patients aged 18 years and older from 2003-2018. The continuous variable OBS was converted into categorical variables by quartiles, and weighted multiple logistic regression analyses and restricted triple spline models were used to explore the relationships. We also performed subgroup analyses and interaction tests to verify the stability of the results.

Results

A total of 5389 participants were included, representing 23.6 million non-institutionalized US residents. The results from both multivariate logistic regression analysis and restricted cubic spline models indicated that OBS and dietary OBS levels were negatively associated with the risk of DKD, low-eGFR, and albuminuria, without finding a significant correlation between lifestyle OBS and these clinical outcomes. Compared to the lowest OBS quartile group, the prevalence risk of DKD (OR = 0.61, 95% CI: 0.46-0.80), low-eGFR (OR = 0.46, 95% CI: 0.33-0.64) and albuminuria (OR = 0.68, 95% CI: 0.51-0.92) decreased by 39%, 54% and 32%, respectively, in the highest OBS quartile group. The results remained stable in subgroup analyses and no interaction between subgroups was found.

Conclusion

Higher levels of OBS and dietary OBS were associated with a lower risk of DKD, low-eGFR, and albuminuria. These findings provided preliminary evidence for the importance of adhering to an antioxidant-rich diet and lifestyle among individuals with diabetes.
Soil temperature prediction based on explainable artificial intelligence and LSTM
Authors: Geng Qingtian , Wang Leilei , Li Qingliang
Published: July 2024

Soil temperature is a key parameter in many disciplines, and its research has important practical significance. In recent years, the prediction of soil temperature by deep learning has achieved good results. However, deep learning is difficult to popularize in practical use because of its opacity. This study aims to interpret and analyze the Long Short Term Memory Network (LSTM) model for global soil temperature prediction using SHapley Additive exPlanation (SHAP), Permutation Importance (PI) and Partial Dependence Plot (PDP). The results show that Temperature of air at 2 m above the surface of land has the greatest influence on the prediction of soil temperature, and its SHAP and PI characteristic values have significant seasonality. Meanwhile, radiation also has a certain influence on the prediction results. There was a significant positive correlation between the temperature of 2 m and the soil temperature. The explanatory insights provided in this paper enhance the transparency and confidence of the model, which promotes the applicability of soil temperature prediction models in relevant fields.
Transcriptomic analysis for the gamma-ray-induced sweetpotato mutants with altered stem growth pattern
Authors: Lee Hyeong-Un , Shim Sangrea , Chung Mi Nam , Lee Taeyoung , Park Won , Kim Tae Hwa , Lee Kyo Hwui , Woo Koan Sik , Nam Sang-Sik , Kim Moon Young , Lee Suk-Ha
Published: July 2024

Introduction

Sweetpotato faces breeding challenges due to physiological and genomic issues. Gamma radiation is a novel approach for inducing genetic variation in crops. We analyzed the transcriptomic changes in gamma ray-induced sweetpotato mutants with altered stem development compared with those in the wild-type 'Tongchaeru’ cultivar.

Methods

RNA sequencing analyses were performed to identify changes in the expression of genes related to stem development.

Results

Transcriptomic analysis identified 8,931 upregulated and 6,901 downregulated genes, including the upregulation of the auxin-responsive SMALL AUXIN UP RNA (SAUR) and three PHYTOCHROME INTERACTING FACTOR 4 (PIF4) genes. PIF4 is crucial for regulating the expression of early auxin-responsive SAUR genes and stem growth in Arabidopsis thaliana. In the mutant, several genes related to stem elongation, including PIF4 and those involved in various signaling pathways such as auxin and gibberellin, were upregulated.

Discussion

Our results suggest that gamma ray-induced mutations influence auxin-dependent stem development by modulating a complex regulatory network involving the expression of PIF4 and SAUR genes, and other signaling pathways such as gibberellin and ethylene signaling genes. This study enhances our understanding of the regulatory mechanisms underlying stem growth in sweetpotato, providing valuable insights for genomics-assisted breeding efforts.
Combined maternal KIR2DL4 and fetal HLA-G polymorphisms were associated with preeclampsia in a Han Chinese population
Authors: Ma Yantuanjin , Qian Yuan , Jiang Hong , Meng Haiyun , Wang Yang , Yang Yuling
Published: July 2024

Preeclampsia is the main cause of maternal and infant mortality and morbidity during pregnancy. Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) and human leukocyte antigen G (HLA-G) play crucial roles in immune tolerance at the maternal-fetal interface. In this case‒control study, 154 maternal–fetal pairs were recruited, including 74 pairs with preeclampsia (56 of 74 pairs from family triads) and 80 pairs with a normal pregnancy (78 of 80 pairs from family triads). SNaPshot technology was used to detect genetic polymorphisms for 7 TagSNPs in the KIR2DL4 and HLA-G genes. Among the fetal HLA-G gene polymorphisms, rs9380142 (A vs. G: OR = 2.802, 95% CI = 1.761–4.458) and rs1063320 (G vs. C: OR = 1.807, 95% CI = 1.144–2.852) differed between the preeclampsia group and the control group. The transmission disequilibrium test (TDT) suggested that the differences in the rs9380142G/A polymorphism in foetuses between preeclampsia triads and control triads were due to differences in transmission from the parents (P = 0.001). There was no significant difference in the distribution of maternal KIR2DL4 alleles or genotype frequency between the preeclampsia group and the control group. Gene‒gene interaction analysis revealed that the combined genotypes of maternal rs649216-CC and fetal rs9380142-GG, maternal rs1051456-CG/GG and fetal rs9380142-GG, maternal rs34785252-CC and fetal rs9380142-AA/GA, and maternal rs34785252-CC/AA and fetal rs9380142-GG were associated with a significantly lower risk of preeclampsia. Therefore, this study suggested that the combination of maternal KIR2DL4 and fetal HLA-G polymorphisms was associated with preeclampsia in a Han Chinese population.
Crosstalk between gut microbiota and host immune system and its response to traumatic injury
Authors: Ullah Hanif , Arbab Safia , Tian Yali , Chen Yuwen , Liu Chang-qing , Li Qijie , Li Ka
Published: July 2024

Millions of microorganisms make up the complex microbial ecosystem found in the human gut. The immune system’s interaction with the gut microbiota is essential for preventing inflammation and maintaining intestinal homeostasis. Numerous metabolic products that can cross-talk between immune cells and the gut epithelium are metabolized by the gut microbiota. Traumatic injury elicits a great and multifaceted immune response in the minutes after the initial offense, containing simultaneous pro- and anti-inflammatory responses. The development of innovative therapies that improve patient outcomes depends on the gut microbiota and immunological responses to trauma. The altered makeup of gut microbes, or gut dysbiosis, can also dysregulate immunological responses, resulting in inflammation. Major human diseases may become more common as a result of chronic dysbiosis and the translocation of bacteria and the products of their metabolism beyond the mucosal barrier. In this review, we briefly summarize the interactions between the gut microbiota and the immune system and human disease and their therapeutic probiotic formulations. We also discuss the immune response to traumatic injury.
Porcine γδ T cells express cytotoxic cell-associated markers and display killing activity but are not selectively cytotoxic against PRRSV- or swIAV-infected macrophages
Authors: Bettin Leonie , Darbellay Joseph , van Kessel Jill , Dhar Neeraj , Gerdts Volker
Published: July 2024

Background

Gamma-delta (γδ) T cells are a major immune cell subset in pigs. Approximately 50% of circulating T cells are γδ T cells in young pigs and up to 30% in adult sows. Despite this abundance, the functions of porcine γδ T cells are mostly unidentified. In humans and mice, activated γδ T cells exhibit broad innate cytotoxic activity against a wide variety of stressed, infected, and cancerous cells through death receptor/ligand-dependent and perforin/granzyme-dependent pathways. However, so far, it is unknown whether porcine γδ T cells have the ability to perform cytotoxic functions.

Methods

In this study, we conducted a comprehensive phenotypic characterization of porcine γδ T cells isolated from blood, lung, and nasal mucosa. To further analyze the cytolytic potential of γδ T cells, in vitro cytotoxicity assays were performed using purified γδ T cells as effector cells and virus-exposed or mock-treated primary porcine alveolar macrophages as target cells.

Results

Our results show that only CD2+ γδ T cells express cytotoxic markers (CD16, NKp46, perforin) with higher perforin and NKp46 expression in γδ T cells isolated from lung and nasal mucosa. Moreover, we found that γδ T cells can exhibit cytotoxic functions in a cell-cell contact and degranulation-dependent manner. However, porcine γδ T cells did not seem to specifically target Porcine Reproductive and Respiratory Syndrome Virus or swine Influenza A Virus-infected macrophages, which may be due to viral escape mechanisms.

Conclusion

Porcine γδ T cells express cytotoxic markers and can exhibit cytotoxic activity in vitro. The specific mechanisms by which porcine γδ T cells recognize target cells are not fully understood but may involve the detection of cellular stress signals.
Successful treatment of relapsed and refractory CIDP with ofatumumab: a first case report
Authors: Wang Jian , Xiang QunHong
Published: July 2024

Background

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous but treatable immune-mediated neuropathy. Ofatumumab (OFA) is a fully human anti-CD20 monoclonal antibody that has shown promising efficacy in central demyelinating diseases, such as multiple sclerosis (MS). However, there is a lack of studies on the usage of OFA in peripheral demyelinating diseases, particularly CIDP. A case of relapsed and refractory CIDP with an ineffective response to conventional immunotherapy and intolerance to rituximab (RTX) but a positive response to subcutaneous injections of OFA is presented.

Case presentation

The patient, a 46-year-old man diagnosed with CIDP, received high-dose intravenous methylprednisolone, intravenous immunoglobulin (IVIG), and plasma exchange(PE) during the acute phase of the disease, and long-term oral administration of prednisone, azathioprine (AZA), and mycophenolate mofetil (MMF) during the remission phase. However, the patient suffered six relapses over a five-year period, and because of these, along with an ineffective response to conventional immunotherapy, and intolerance to RTX, subcutaneous injections of OFA were selected as a prophylactic treatment against relapses. After a total of six injections of OFA, CD19+B cells were substantially depleted. The patient has been followed for more than 23 months without relapse.

Conclusions

This case demonstrates the effectiveness and good tolerability of OFA in the treatment of relapsed and refractory CIDP. Further studies are needed to investigate the efficacy and safety of OFA in patients with relapsed and refractory CIDP, especially in those who have shown an ineffective response to conventional immunotherapy and are intolerant to RTX.
Dynamic modulus characteristics and prediction model of semi-flexible materials filled with high-performance cement paste
Authors: Wang Deyong , Li Guoxun , Jiang Lingang , Zhang Huaizhi , Zhang Jie , Si Xiaowei
Published: July 2024

The dynamic modulus of asphalt mixture is an important factor in the design of asphalt pavement, and many scholars have proposed different models for estimating the dynamic modulus of asphalt mixture, but there are almost no studies on the prediction of the dynamic modulus of semi-flexible materials. In order to analyze and estimate the dynamic modulus of semi-flexible materials, we set up a high-performance cementitious paste (HPCP) semi-flexible material and a reference group Stone Mastic Asphalt (SMA-16) under multiple conditions, first measured its dynamic modulus in the laboratory, and analyzed the dynamic modulus characteristics of the material, and then used the equation the estimation equation proposed by Witczak et al. (Witczak1-37A) as a benchmark to introduce a new parameter, grouting mass ratio (Pb) to develop a Witczak-G prediction model to compare and validate the predicted dynamic modulus with the measured values. The results show that compared with SMA-16, HPCP semi-flexible material exhibits higher dynamic modulus and lower phase angle, and its temperature sensitivity and deformation resistance are significantly better than those of SMA-16. Under the influence of porosity and Pb factor, the dynamic modulus is positively correlated with both factors, and the phase angle increases first and then decreases, showing strong elastic properties. In this paper, we propose a dynamic modulus prediction model based on viscosity and Pb, Witczak-G, which predicts the highest coefficient of determination (R2) of the predicted dynamic modulus as high as 0.99 after initial fitting and validation, which indicates that the Witczak-G model is suitable for predicting the dynamic modulus of semi-flexible materials injected with HPCP.
Application of optimizing advanced encryption standard encryption algorithm in secure communication of vehicle controller area network bus
Authors: Mu Chenzhe
Published: July 2024

Introduction: As the main means of information exchange within vehicles, the safety of the controller area network bus directly affects the safe operation of the vehicle and the safety of passengers’ lives and property.

Methods: To enhance its secure communication function, this study utilizes advanced encryption standard algorithms and improves the S-box of the algorithm to solve problems such as extended processing time. A secure communication system for the local area network bus of the vehicle controller is designed based on optimized advanced encryption standard algorithms.

Results and Discussion: The results showed that when the file size was 200MB, the encryption and decryption time spent by the research method was 469.8 s and 528.5 s, respectively, which are significantly lower than traditional methods. In the simulation results, under both non-encrypted and encrypted transmission, the information remained intact throughout the entire transmission process. This indicated that the optimization algorithm effectively reduced encryption processing time and system resource consumption while ensuring data confidentiality and integrity. The new system meets the security requirements of the local area network bus of vehicle-mounted controllers.

Conclusion: This study not only enhances the security of in-vehicle networks but also promotes the application and development of related encryption technologies in the field of vehicle networking. It provides strong technical support for the further development of vehicle networking and the safe operation of intelligent vehicles.
Extended analysis on peripheral blood cytokines correlated with hepatitis B virus viral load in chronically infected patients – a systematic review and meta-analysis
Authors: Manea Marina , Mărunțelu Ion , Constantinescu Ileana
Published: July 2024

Background

Hepatitis B Virus (HBV) can affect life quality. Monitoring and understanding the fluctuations of the HBV level of viremia related to the intricate immune activity of the host helps in the development of new treatment strategies and evaluation patterns. This meta-analysis presents the correlations between cytokines and the level of viremia in chronic HBV patients for a better comprehension of the immune mechanisms behind this infection.

Methods

We used PRISMA guidelines for this meta-analysis. The databases assessed were PUBMED, WEB OF SCIENCE, SCOPUS, and Cochrane Library. ZOTERO and PlotDigitizer helped the systematic research process. We extracted information related to the correlations between cytokines and the HBV-DNA level. Effect measures included comparisons between standardized mean differences and correlation coefficients. We evaluated retrieved articles with the Newcastle-Ottawa Quality Assessment Scale (NOS). The R 4.2.2 software displayed the statistical calculation and graphical representations.

Results

From 58,169 records, we extracted 16 articles with 32 different cytokine determinations. The main interleukins included in detection panels were IL-10 and IL-21. The meta-correlation analysis comprised 1,199 chronic HBV patients. The standardized mean difference between cytokine levels in HBV patients and healthy controls was 0.82 (95% CI = [−0.19, 1.84], p = 0.11). We observed a significant, fair, pooled correlation coefficient between IL-10, IL-9, and the viral load (r = 0.52, 95% CI = [0.19, 0.85]).

Conclusion

This meta-analysis brings novelty because it gives a first rigorous systematic look at multiple studies with many cytokines. Our research approaches a debatable issue and gives a possible solution for settling controversies. Future studies can arise towards understanding the immune disruption in HBV and the development of new, improved assays for prognosis.
Advances in hepatocellular carcinoma drug resistance models
Authors: Xiang Yien , Wu Jun , Qin Hanjiao
Published: July 2024

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Surgery has been the major treatment method for HCC owing to HCC’s poor sensitivity to radiotherapy and chemotherapy. However, its effectiveness is limited by postoperative tumour recurrence and metastasis. Systemic therapy is applied to eliminate postoperative residual tumour cells and improve the survival of patients with advanced HCC. Recently, the emergence of various novel targeted and immunotherapeutic drugs has significantly improved the prognosis of advanced HCC. However, targeted and immunological therapies may not always produce complete and long-lasting anti-tumour responses because of tumour heterogeneity and drug resistance. Traditional and patient-derived cell lines or animal models are used to investigate the drug resistance mechanisms of HCC and identify drugs that could reverse the resistance. This study comprehensively reviewed the established methods and applications of in-vivo and in-vitro HCC drug resistance models to further understand the resistance mechanisms in HCC treatment and provide a model basis for possible individualised therapy.
Two colistin resistance-producing Aeromonas strains, isolated from coastal waters in Zhejiang, China: characteristics, multi-drug resistance and pathogenicity
Authors: Chen Hong-Xian , Chen Fang-Jie , Zhou Qian-Jin , Shang Shi-Lin , Tang Biao , Xu Zhong-Jie , Duan Li-Jun , Jin Jing-Lei , Xu Gui-Zong , Yan Mao-Cang , Chen Jiong
Published: July 2024

Introduction

Aeromonas spp. are ubiquitous inhabitants of ecosystems, and many species are opportunistically pathogenic to humans and animals. Multidrug-resistant (MDR) Aeromonas species have been widely detected in hospitals, urban rivers, livestock, and aquatic animals.

Results

In this study, we identified two Aeromonas isolates, namely Aeromonas veronii 0728Q8Av and Aeromonas caviae 1029Y16Ac, from coastal waters in Zhejiang, China. Both isolates exhibited typical biochemical characteristics and conferred MDR to 11 kinds of antibiotics, remaining susceptible to ceftazidime. Whole-genome sequencing revealed that both isolates harbored multiple antibiotic resistance genes (ARGs) and several mobile genetic elements (MGEs) on the chromosomes, each containing a resistance genomic island (GI), a typical class 1 integron, a transposon, and various insertion sequences (ISs). Most ARGs were situated within the multiple resistance GI, which contained a class 1 integron and a transposon in both Aeromonas isolates. Furthermore, a chromosomal mcr-3.16 gene was identified in A. veronii 0728Q8Av, while a chromosomal mcr-3.3 was found in A. caviae 1029Y16Ac. Both mcr-3 variants were not located within but were distanced from the multidrug resistance GI on the chromosome, flanking by multiple ISs. In addition, a mcr-3-like was found adjacent to mcr-3.16 to form a tandem mcr-3.16-mcr-3-like-dgkA structure; yet, Escherichia coli carrying the recombinants of mcr-3-like did not exhibit resistance to colistin. And an incomplete mcr-3-like was found adjacent to mcr-3.3 in A. caviae 1029Y16Ac, suggesting the possibility that mcr-3 variants originated from Aeromonas species. In vivo bacterial pathogenicity test indicated that A. veronii 0728Q8Av exhibited moderate pathogenicity towards infected ayu, while A. caviae 1029Y16Ac was non-virulent.

Discussion

Thus, both Aeromonas species deserve further attention regarding their antimicrobial resistance and pathogenicity.
Review of the protist Labyrinhula spp. and its relationship to seagrass disease under the influence of anthropogenic activities
Authors: Wang Qiuzhen , Yu Xinping , He Yike , Zhang Yong , Hui Ruixue , Ye Huike , Wang Caili , Bai Mohan
Published: July 2024

Anthropogenic activities are driving significant changes in coastal ecological environments, increasingly spotlighting microorganisms associated with seagrass bed ecosystems. Labyrinthula is primarily recognized as a saprophytic protist associated with marine detritus, and it also acts as an opportunistic pathogen affecting marine algae, terrestrial plants and mollusks, especially in coastal environments. The genus plays a key role in the decomposition of marine detritus, facilitated by its interactions with diatoms and through the utilization of a diverse array of carbohydrate-active enzymes to decompose seagrass cell walls. However, human activities have significantly influenced the prevalence and severity of seagrass wasting disease (SWD) through factors such as climate warming, increased salinity and ocean acidification. The rise in temperature and salinity, exacerbated by human-induced climate change, has been shown to increase the susceptibility of seagrass to Labyrinthula, highlighting the adaptability of pathogen to environmental stressors. Moreover, the role of seagrass in regulating pathogen load and their immune response to Labyrinthula underscore the complex dynamics within these marine ecosystems. Importantly, the genotype diversity of seagrass hosts, environmental stress factors and the presence of marine organisms such as oysters, can influence the interaction mechanisms between seagrass and Labyrinthula. Besides, these organisms have the potential to both mitigate and facilitate pathogen transmission. The complexity of these interactions and their impacts driven by human activities calls for the development of comprehensive multi-factor models to better understand and manage the conservation and restoration of seagrass beds.
Interhospital transfer dynamics for patients with intracranial hemorrhage in Massachusetts
Authors: Patel Ruchit V. , Tong Lilin , Molyneaux Bradley J. , Patel Nirav J. , Aziz-Sultan Mohammed A. , Dhand Amar , Bi Wenya Linda
Published: July 2024

Introduction

Intracranial hemorrhages present across a spectrum of clinical phenotypes, with many patients transferred across hospitals to access higher levels of neurocritical care. We sought to characterize patient dispositions following intracranial hemorrhage and examine disparities associated with interhospital transfers.

Methods

Using the Healthcare Cost and Utilization Project database, we mapped and identified factors influencing the likelihood of patient transfers and receipt of specialist interventional procedures following intracranial hemorrhage.

Results

Of 11,660 patients with intracranial hemorrhage, 59.4% had non-traumatic and 87.5% single compartment bleeds. After presentation, about a quarter of patients were transferred to another facility either directly from the ED (23.0%) or after inpatient admission (1.8%). On unadjusted analysis, patients who were white, in the upper income quartiles, with private insurance, or resided in suburban areas were more frequently transferred. After adjusting for patient-and hospital-level variables, younger and non-white patients had higher odds of transfer. Hospital capabilities, residence location, insurance status, and prior therapeutic relationship remained as transfer predictors. Transferred patients had a similar hospital length of stay compared to admitted patients, with 43.1% having no recorded surgical or specialist interventional procedure after transfer.

Discussion

Our analysis reveals opportunities for improvement in risk stratification guiding transfers, as well as structural challenges likely impacting transfer decisions.
J-shaped associations of pan-immune-inflammation value and systemic inflammation response index with stroke among American adults with hypertension: evidence from NHANES 1999–2020
Authors: Chen Junchen , Luo Cheng , Tan Dianhui , Li Yong
Published: July 2024

Introduction

Stroke, a leading cause of death and disability worldwide, is primarily ischemic and linked to hypertension. Hypertension, characterized by systemic chronic inflammation, significantly increases stroke risk. This study explores the association of novel systemic inflammatory markers (SII, PIV, SIRI) with stroke prevalence in hypertensive U.S. adults using NHANES data.

Methods

We analyzed data from hypertensive participants in the NHANES 1999–2020 survey, excluding those under 20, pregnant, or with missing data, resulting in 18,360 subjects. Systemic inflammatory markers (SII, PIV, SIRI) were calculated from blood counts. Hypertension and stroke status were determined by self-report and clinical measurements. Covariates included sociodemographic, lifestyle, and medical history factors. Weighted statistical analyses and multivariate logistic regression models were used to explore associations, with adjustments for various covariates. Ethical approval was obtained from the NCHS Ethics Review Board.

Results

In a cohort of 18,360 hypertensive individuals (mean age 56.652 years), 7.25% had a stroke. Stroke patients were older, had lower PIR, and were more likely to be female, single, less educated, smokers, non-drinkers, physically inactive, and have diabetes and CHD. Multivariate logistic regression showed that SII was not significantly associated with stroke. However, PIV and SIRI were positively associated with stroke prevalence. Each unit increase in lnPIV increased stroke odds by 14% (OR = 1.140, p = 0.0022), and lnSIRI by 20.6% (OR = 1.206, p = 0.0144). RCS analyses confirmed J-shaped associations for lnPIV and lnSIRI with stroke. Stratified analyses identified gender and smoking as significant effect modifiers. Smoking was significantly associated with elevated PIV, SIRI, and SII levels, especially in current smokers.

Conclusion

Elevated PIV and SIRI levels significantly increase stroke prevalence in hypertensive individuals, notably among males and smokers. A predictive model with PIV, SIRI, and sociodemographic factors offers strong clinical utility.
The effects of whole-body vibration therapy on immune and brain functioning: current insights in the underlying cellular and molecular mechanisms
Authors: Ahuja Gargi , Arauz Y. Laurisa Arenales , van Heuvelen Marieke J. G. , Kortholt Arjan , Oroszi Tamás , van der Zee Eddy A.
Published: July 2024

Whole-body vibration (WBV) therapy is a way of passive exercise in which subjects are exposed to mild and well-controlled mechanical vibrations through a vibrating platform. For a long time, studies have focused on the effects and applications of WBV to enhance musculoskeletal performance in athletes and patients suffering from musculoskeletal disorders. Recent evidence points toward the positive effect of WBV on the brain and its therapeutic potential in brain disorders. Research being done in the field gradually reveals cellular and molecular mechanisms underlying WBV affecting the body and brain. Particularly, the influence of WBV on immune and brain function is a growing field that warrants an up-to-date and integrated review. Immune function is closely intertwined with brain functioning and plays a significant role in various brain disorders. Dysregulation of the immune response is linked to conditions such as neuroinflammation, neurodegenerative diseases, and mood disorders, highlighting the crucial connection between the immune system and the brain. This review aims to explore the impact of WBV on the cellular and molecular pathways involved in immune and brain functions. Understanding the effects of WBV at a cellular and molecular level will aid in optimizing WBV protocols to improve its therapeutic potential for brain disorders.
Direct training high-performance deep spiking neural networks: a review of theories and methods
Authors: Zhou Chenlin , Zhang Han , Yu Liutao , Ye Yumin , Zhou Zhaokun , Huang Liwei , Ma Zhengyu , Fan Xiaopeng , Zhou Huihui , Tian Yonghong
Published: July 2024

Spiking neural networks (SNNs) offer a promising energy-efficient alternative to artificial neural networks (ANNs), in virtue of their high biological plausibility, rich spatial-temporal dynamics, and event-driven computation. The direct training algorithms based on the surrogate gradient method provide sufficient flexibility to design novel SNN architectures and explore the spatial-temporal dynamics of SNNs. According to previous studies, the performance of models is highly dependent on their sizes. Recently, direct training deep SNNs have achieved great progress on both neuromorphic datasets and large-scale static datasets. Notably, transformer-based SNNs show comparable performance with their ANN counterparts. In this paper, we provide a new perspective to summarize the theories and methods for training deep SNNs with high performance in a systematic and comprehensive way, including theory fundamentals, spiking neuron models, advanced SNN models and residual architectures, software frameworks and neuromorphic hardware, applications, and future trends.
Physiotherapy-assisted overground exoskeleton use: mixed methods feasibility study protocol quantifying the user experience, as well as functional, neural, and muscular outcomes in children with mobility impairments
Authors: Bradley Stefanie S. , de Holanda Ledycnarf Januario , Chau Tom , Wright F. Virginia
Published: July 2024

Background

Early phase research suggests that physiotherapy paired with use of robotic walking aids provides a novel opportunity for children with severe mobility challenges to experience active walking. The Trexo Plus is a pediatric lower limb exoskeleton mounted on a wheeled walker frame, and is adjustable to fit a child’s positional and gait requirements. It guides and powers the child’s leg movements in a way that is individualized to their movement potential and upright support needs, and can provide progressive challenges for walking within a physiotherapy-based motor learning treatment paradigm.

Methods

This protocol outlines a single group mixed-methods study that assesses the feasibility of physiotherapy-assisted overground Trexo use in school and outpatient settings during a 6-week physiotherapy block. Children ages 3–6 years (n= 10; cerebral palsy or related disorder, Gross Motor Function Classification System level IV) will be recruited by circle of care invitations to participate. Study indicators/outcomes will focus on evaluation of: (i) clinical feasibility, safety, and acceptability of intervention; (ii) pre-post intervention motor/functional outcomes; (iii) pre-post intervention brain structure characterization and resting state brain connectivity; (iv) muscle activity characterization during Trexo-assisted gait and natural assisted gait; (v) heart rate during Trexo-assisted gait and natural assisted gait; and (vi) user experience and perceptions of physiotherapists, children, and parents.

Discussion

This will be the first study to investigate feasibility indicators, outcomes, and experiences of Trexo-based physiotherapy in a school and outpatient context with children who have mobility challenges. It will explore the possibility of experience-dependent neuroplasticity in the context of gait rehabilitation, as well as associated functional and muscular outcomes. Finally, the study will address important questions about clinical utility and future adoption of the device from the physiotherapists’ perspective, comfort and engagement from the children’s perspective, and the impressions of parents about the value of introducing this technology as an early intervention.

Clinical trial registration

https://clinicaltrials.gov, identifier NCT05463211
Phase II study of nab-paclitaxel with gemcitabine for relapsed/refractory small cell lung cancer
Authors: Byrne Margaret M. , Sutamtewagul Grerk , Zeitler William , Mott Sarah L. , Zamba Gideon K.D. , Kojadinovic Arsenije , Zhang Jun , Abu-Hejleh Taher , Clamon Gerald , Furqan Muhammad
Published: July 2024

Background

Patients with small cell lung cancer (SCLC) often respond to first-line chemoimmunotherapy. However, relapse is inevitable and is associated with a poor prognosis. Treatments for relapsed SCLC, such as lurbinectedin and topotecan, are limited by modest efficacy and significant hematologic adverse events, leaving a need for newer therapeutic agents or regimens. The combination of gemcitabine and nab-paclitaxel is active and safe in other types of malignancies, such as pancreatic cancer.

Patients and methods

We conducted a phase II trial evaluating the efficacy and safety of gemcitabine and nab-paclitaxel in patients with relapsed/refractory SCLC. The primary endpoint was objective response rate (ORR), defined as the proportion of patients with confirmed complete or partial response. Secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety.

Results

Between October 2016 and May 2021, 32 patients were enrolled. Patients were followed for a median of 9.3 months (range 1.8–65.2). Median age was 65 years (range 48–81). Fifty percent of patients were female. Fifty-three percent of patients had platinum-resistant/refractory relapsed SCLC. The ORR was 28.1% (95% confidence interval [CI] 15.5–100%). Median PFS was 2.9 months (95% CI 2.4–3.6), and median OS was 9.3 months (95% CI 5.2–12.4). Seven patients (21.9%) developed grade 3 or 4 neutropenia.

Conclusion

Our study showed that the combination of gemcitabine and nab-paclitaxel led to encouraging outcomes in relapsed/refractory SCLC. Further studies are needed to compare this combination with other treatments used for relapsed SCLC, including lurbinectedin, temozolomide, and topotecan.

Clinical trial registration

https://clinicaltrials.gov/study/NCT02769832?cond=NCT02769832&rank=1, identifier NCT02769832.
Challenges in overcoming advanced-stage or relapsed refractory extranodal NK/T-cell lymphoma: meta-analysis of individual patient data
Authors: Kim Tong Yoon , Kim Tae Jung , Han Eun Ji , Min Gi June , Jeon Youngwoo , Cho Seok-Goo
Published: July 2024

Introduction

Extranodal NK/T-cell lymphoma (ENKTCL), a non-Hodgkin lymphoma, is known for its destructive local impact on nasal structures and systemic induction of inflammatory cytokines. Concurrent treatment with radiation and nonanthracycline- based chemotherapy has improved survival rates in patients with localized disease stages. However, survival outcomes vary significantly in advanced-stage and relapsed or refractory (R/R) cases.

Methods

Therefore, we conducted a meta-analysis using random effects models to assess prognostic factors in advanced or R/R ENKTCL, employing a digital extractor on Kaplan–Meier graphs owing to the scarcity of published prospective trials for these patients.

Results

We observed that patients with advanced ENKTCL treated with Lasparaginase had a median progression-free survival (PFS) of 14.3 months and an overall survival (OS) of 19 months. In R/R ENKTCL, PFS and OS were 11.7 and 15.6 months, respectively. Additionally, OS outcomes in advanced-stage ENKTCL were better in the asparaginase group than that in the non-asparaginase group, with PEG-asparaginase showing superior results compared with that using Lasparaginase. Epstein–Barr Virus (EBV)-DNA positivity in the bloodstream prior to treatment was associated with poor outcomes in advanced-stage ENKTCL, and similar trends were observed in patients with R/R ENKTCL and post-treatment EBV viremia.

Discussion

Collectively, these findings suggest that chemotherapy with Lasparaginase or PEG-asparaginase can enhance survival in advanced or R/R ENKTCL. However, future strategies must be developed to effectively suppress EBV viremia and achieve a deep response toward tumor eradication.
Association of extreme hyperoxemic events and mortality in pediatric critical care: an observational cohort study
Authors: Bachman Thomas E. , Newth Christopher J. L. , Ross Patrick A. , Patel Nimesh , Bhalla Anoopindar
Published: July 2024

Objective

Our aim was to confirm whether extreme hyperoxemic events had been associated with excess mortality in our diverse critical care population.

Methods

Retrospective analysis of 9 years of data collected in the pediatric and cardiothoracic ICUs in Children's Hospital Los Angeles was performed. The analysis was limited to those mechanically ventilated for at least 24 h, with at least 1 arterial blood gas measurement. An extreme hyperoxemic event was defined as a PaO2 of ≥300 torr. Multivariable logistic regression was used to assess the association of extreme hyperoxemia events and mortality, adjusting for confounding variables. Selected a-priori, these were Pediatric Risk of Mortality III predicted mortality, general or cardiothoracic ICU, number of blood gas measurements, as well as an abnormal blood gas measurements (pH < 7.25, pH > 7.45, and PaO2 < 50 torr).

Results

There were 4,003 admissions included with a predicted mortality of 7.1% and an actual mortality of 9.7%. Their care was associated with 75,129 blood gas measurements, in which abnormal measurements were common. With adjustments for these covariates, any hyperoxemic event was associated with excess mortality (p < 0.001). Excess mortality increased with multiple hyperoxemic events (p < 0.046). Additionally, treatment resulting in SpO2 > 98% markedly increased the risk of a hyperoxemic event.

Conclusion

Retrospective analysis of critical care admissions showed that extreme hyperoxemic events were associated with higher mortality. Supplemental oxygen levels resulting in SpO2 > 98% should be avoided.
Synergistic antitumor activity of baicalein combined with almonertinib in almonertinib-resistant non-small cell lung cancer cells through the reactive oxygen species-mediated PI3K/Akt pathway
Authors: Chen Teng , Zhang Pei , Cong Xiao-Fan , Wang Yuan-Yuan , Li Shuo , Wang Hao , Zhao Su-Rong , Sun Xiao-Jin
Published: July 2024

Introduction

Almonertinib is an important third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) exhibiting high selectivity to EGFR-sensitizing and T790M-resistant mutations. Almonertinib resistance is a major obstacle in clinical use. Baicalein possesses antitumor properties, but its mechanism of antitumor action against almonertinib-resistant non-small cell lung cancer (NSCLC) remains unelucidated.

Methods

CCK-8 assay was used to examine the survival rate of H1975/AR and HCC827/AR cells following treatment for 24 h with different concentrations of baicalein, almonertinib or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/Akt signaling pathway were observed in baicalein- and/or almonertinib-treated cells. A nude mouse model bearing subcutaneous HCC827/AR cell xenograft were treated with baicalein (20 mg/kg) or almonertinib (15 mg/kg), and the tumor volume and body mass changes was measured.

Results

Both baicalein and almonertinib represses the viability of HCC827/AR and H1975/AR cells in a concentration-dependent manner. Compared with baicalein or almonertinib alone, the combined application of the two drugs dramatically attenuates cell proliferation; triggers apoptosis; causes cleavage of Caspase-3, PARP, and Caspase-9; downregulates the protein expressions of p-PI3K and p-Akt; and significantly inhibits tumor growth in nude mice. Furthermore, baicalein combined with almonertinib results in massive accumulation of reactive oxygen species (ROS) and preincubation with N-acetyl-L-cysteine (ROS remover) prevents proliferation as well as inhibits apoptosis induction, with partial recovery of the decline of p-PI3K and p-Akt.

Discussion

The combination of baicalein and almonertinib can improve the antitumor activity in almonertinib-resistant NSCLC through the ROS-mediated PI3K/Akt pathway.
Efficacy and safety of HAIC combined with tyrosine kinase inhibitors versus HAIC monotherapy for advanced hepatocellular carcinoma: a multicenter propensity score matching analysis
Authors: Yang Miaomiao , Jiang Xiongying , Liu Huan , Zhang Qingyu , Li Jing , Shao Li , Zhao Lei
Published: July 2024

Purpose

This study aimed to assess the clinical efficacy and safety of the combined approach involving hepatic arterial infusion chemotherapy (HAIC) and tyrosine kinase inhibitors (TKIs) for the treatment of advanced hepatocellular carcinoma (HCC).

Patients and methods

In this multicenter retrospective study conducted from January 2020 to December 2023, we reviewed advanced HCC patients who were treated either with HAIC alone or with a combination of HAIC and TKIs. To address initial disparities between the two groups, we employed propensity score matching (PSM). Tumor response evaluation was performed following RECIST 1.1 criteria. We compared survival outcomes, including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), between the two treatment groups. Safety assessments were conducted for all patients.

Results

Following the eligibility review, 138 patients underwent combined treatment with HAIC and TKIs (HT group), while 198 patients received HAIC monotherapy (HA group) and met the inclusion criteria for enrollment in this study. After PSM, 107 patients were assigned to each group. The HT group exhibited a longer median OS (18.0 versus 8.8 months; hazard ratio [HR], 0.52, p < 0.001) compared to the HA group. Median PFS was also longer in the HT group, although without statistical significance (6.0 versus 4.7 months; HR, 0.85, p = 0.265). The HT group demonstrated a higher ORR (41.1% versus 25.2%; p = 0.020). No significant differences were observed between the two groups in the incidence of all adverse events (AEs) or grade 3/4 AEs (any grade: 81.2% for HT versus 78.8% for HA, p = 0.68; grade 3/4: 18.1% for HT versus 13.6% for HA, p = 0.29). Importantly, all AEs were manageable and acceptable. Notably, no grade 5 AEs occurred in either group.

Conclusion

Combination therapy involving HAIC and TKIs effectively prolonged survival in advanced HCC patients. It represented a preferable alternative to HAIC monotherapy, with manageable safety.