bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of oleandrin and PBI-05204 against viruses of importance to commercial pig health management
Authors: Newman Robert A. , Abdelsalam Karim , Buterbaugh Robin , Sastry K. Jagannadha
Published: June 2024

Background

Infection by porcine respiratory and reproductive syncytial virus (PRRSV), swine influenza virus (SIV) and porcine epidemic diarrhea (PEDV) adversely affect worldwide pig production. Because effective control remains elusive the present research was designed to explore the in vitro antiviral activity of oleandrin and an N. oleander extract (PBI-05204) against each porcine virus.

Methods

Monkey kidney (MARK-145) cells, Madin-Darby canine kidney cells (MDCK), and African green monkey kidney cells (VERO 76) were used for in vitro culture systems for PRRSV, SIV and PEDV, respectively. Cytotoxicity was established using serial dilutions of oleandrin or PBI-05204. Noncytotoxic concentrations of each product were used either prior to or at 12 h and 24 h following exposure to corresponding viruses. Infectious virus titers were also determined.

Results

Oleandrin and PBI-05204 demonstrated strong antiviral activity against PRRSV, SIV and PEDV when added prior to or following infection of cells. Determination of viral loads by PCR demonstrated a decline in PRRSV replication reaching 99.57% and 99.79% for oleandrin and PBI-05204, respectively, and decrease of 95.36% and 99.54% in infectivity of progeny virus in PRRSV infected cultures. Similarly, oleandrin tested against SIV and PEDV was effective in near complete inhibition of infectious virus production.

Conclusion

The research demonstrates the potency of oleandrin and PBI-05204 to inhibit infectivity of three important porcine viruses. These data showing non-toxic concentrations of oleandrin as a single common agent for inhibiting infectivity of the three different porcine viruses tested here support further investigation of antiviral efficacy and possible in vivo use.
Fighting erasure and dispossession in the San Francisco Bay Area: putting archaeology to work for the Muwekma Ohlone Tribe
Authors: Panich Lee M. , Arellano Monica V. , Wilcox Michael , Flores Gustavo , Connell Samuel
Published: June 2024

The Muwekma Ohlone Tribe has long been involved in the archaeology and stewardship of their ancestral homelands, both through their own cultural resource management (CRM) firm and though collaborations with academic and CRM archaeologists. In this article, we build on the past 40 years of archaeological collaborations in the southern San Francisco Bay region and offer examples of how archaeologists can support tribal heritage and environmental stewardship by using the traditional purview of material culture in combination with a broader array of evidence and concerns. As presented in our brief case studies, the Muwekma Ohlone Tribe and scholars are working together to reclaim tribal heritage and promote Native stewardship in a cultural landscape that has been marred by more than 250 years of dispossession. We examine this work in the context of the renaming of ancestral sites, the public interpretation of Native heritage associated with Mission Santa Clara de Asís, archival research into the history of Indigenous resistance, as well as collaborative efforts to awaken traditional ecological knowledge in service of the Tribe's stewardship and land management goals.
Effect of progestin on thyroid function in female Wistar rats
Authors: Xie Honglei , Qian Tingting , Liu Lanchun , Sun Rong , Che Wenjing , Zhao Meng , Hou Xin , Pan Haowen , Su Yue , Li Jia , Dong Xiaoqiu , Liu Peng
Published: June 2024

Introduction

To characterize the influence of female-specific hormones on women’s thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction.

Methods

Sixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal–Wallis test.

Results

Following levonorgestrel gavage, serum free T4 and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (p=0.013 and 0.043). After desogestrel gavage, the serum free T4 and free T3 levels were lower in the experimental group than that in the control group (p=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid.

Discussion

Progestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats’ thyroid.
Association of systemic immune-inflammation index with insulin resistance and prediabetes: a cross-sectional study
Authors: Guo Han , Wan Chuan , Zhu Jingjing , Jiang Xiuxing , Li Shufa
Published: June 2024

Background and Objective

Previous research suggested a relationship between the Systemic Immune-Inflammation Index (SII) and multiple adverse health conditions. However, the role of SII in prediabetes and insulin resistance (IR) remains poorly understood. Therefore, this study aims to explore the potential relationship between SII and prediabetes and IR, providing data support for effective diabetes prevention by reducing systemic inflammation.

Methods

Linear regression models were used to assess the correlation between continuous SII and risk markers for type 2 diabetes (T2D). Subsequently, multivariate logistic regression models and subgroup analyses were employed to evaluate the association between SII tertiles and prediabetes and IR, controlling for various confounding factors. Finally, restricted cubic spline graphs were used to analyze the nonlinear relationship between SII and IR and prediabetes.

Results

After controlling for multiple potential confounders, SII was positively correlated with fasting blood glucose (FBG) (β: 0.100; 95% CI: 0.040 to 0.160), fasting serum insulin (FSI) (β: 1.042; 95% CI: 0.200 to 1.885), and homeostasis model assessment of insulin resistance (HOMA-IR) (β: 0.273; 95% CI: 0.022 to 0.523). Compared to participants with lower SII, those in the highest tertile had increased odds of prediabetes (OR: 1.17; 95% CI: 1.02-1.34; p for trend < 0.05) and IR (OR: 1.35; 95% CI: 1.18 to 1.51; p for trend<0.001).

Conclusions

Our study results demonstrate an elevated association between SII levels and both IR and prediabetes, indicating SII as a straightforward and cost-effective method identifying individuals with IR and prediabetes.
Caloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice
Authors: Rinne Charlotte , Soultoukis George A. , Oveisi Masoome , Leer Marina , Schmidt-Bleek Oskar , Burkhardt Lisa-Marie , Bucher Christian H. , Moussa Eman Abou , Makhlouf Melanie , Duda Georg N. , Saraiva Luis R. , Schmidt-Bleek Katharina , Schulz Tim J.
Published: June 2024

Introduction

Caloric restriction (CR) is a nutritional intervention that increases life expectancy while lowering the risk for cardio-metabolic disease. Its effects on bone health, however, remain controversial. For instance, CR has been linked to increased accumulation of bone marrow adipose tissue (BMAT) in long bones, a process thought to elicit detrimental effects on bone. Qualitative differences have been reported in BMAT in relation to its specific anatomical localization, subdividing it into physiological and potentially pathological BMAT. We here examine the local impact of CR on bone composition, microstructure and its endocrine profile in the context of aging.

Methods

Young and aged male C57Bl6J mice were subjected to CR for 8 weeks and were compared to age-matched littermates with free food access. We assessed bone microstructure and BMAT by micro-CT, bone fatty acid and transcriptomic profiles, and bone healing.

Results

CR increased tibial BMAT accumulation and adipogenic gene expression. CR also resulted in elevated fatty acid desaturation in the proximal and mid-shaft regions of the tibia, thus more closely resembling the biochemical lipid profile of the distally located, physiological BMAT. In aged mice, CR attenuated trabecular bone loss, suggesting that CR may revert some aspects of age-related bone dysfunction. Cortical bone, however, was decreased in young mice on CR and remained reduced in aged mice, irrespective of dietary intervention. No negative effects of CR on bone regeneration were evident in either young or aged mice.

Discussion

Our findings indicate that the timing of CR is critical and may exert detrimental effects on bone biology if administered during a phase of active skeletal growth. Conversely, CR exerts positive effects on trabecular bone structure in the context of aging, which occurs despite substantial accumulation of BMAT. These data suggest that the endocrine profile of BMAT, rather than its fatty acid composition, contributes to healthy bone maintenance in aged mice.
A novel IRF6 gene mutation impacting the regulation of TGFβ2-AS1 in the TGFβ pathway: A mechanism in the development of Van der Woude syndrome
Authors: Zhao Zhiyang , Cui Renjie , Chi Haoshu , Wan Teng , Ma Duan , Zhang Jin , Cai Ming
Published: June 2024

Several mutations in the IRF6 gene have been identified as a causative link to VWS. In this investigation, whole-exome sequencing (WES) and Sanger sequencing of a three-generation pedigree with an autosomal-dominant inheritance pattern affected by VWS identified a unique stop-gain mutation—c.748C>T:p.R250X—in the IRF6 gene that co-segregated exclusively with the disease phenotype. Immunofluorescence analysis revealed that the IRF6-p.R250X mutation predominantly shifted its localization from the nucleus to the cytoplasm. WES and protein interaction analyses were conducted to understand this mutation’s role in the pathogenesis of VWS. Using LC-MS/MS, we found that this mutation led to a reduction in the binding of IRF6 to histone modification-associated proteins (NAA10, SNRPN, NAP1L1). Furthermore, RNA-seq results show that the mutation resulted in a downregulation of TGFβ2-AS1 expression. The findings highlight the mutation’s influence on TGFβ2-AS1 and its subsequent effects on the phosphorylation of SMAD2/3, which are critical in maxillofacial development, particularly the palate. These insights contribute to a deeper understanding of VWS’s molecular underpinnings and might inform future therapeutic strategies.
Navigating collaborative learning across national boundaries: a comparative study of educators’ perspectives in Israel and Turkey
Authors: Pothou Eleni , Eliyahu-Levi Dolly , Sonbahar Begüm , Ganz-Meishar Michal
Published: June 2024

The primary goal of the KIDS4ALLL project was to empower educators to foster a flexible, innovative, and collaborative learning environment within their classrooms. This article delves into teachers’ experiences with implementing collaborative learning during the KIDS4ALLL project. Additionally, it explores how teachers perceived the implementation of the KIDS4ALLL pilot in learning environments across different national educational settings, specifically in Israel and Turkey. Given that both Israel and Turkey have centralized education systems and adhere to a traditional teaching approach, the two research questions offer insights into how the national education context of both countries influences the implementation of the collaborative learning approach of KIDS4ALLL and the experiences of educators. The methodology employed in this study involved semi-structured interviews with 16 educators and participant observation during the two pilots. The findings highlight a sense of fear and uncertainty among educators regarding their ability to conduct lessons in an unfamiliar yet innovative and flexible learning environment. These feelings were accompanied by challenges such as technological and language barriers, sociocultural diversities, and occasional behavioral issues. The results also underscore similarities between the two countries, emphasizing that centralized education systems, teachers’ previous training, curriculum, and available physical space posed challenges to the pilot program’s implementation.
In vitro IL-15-activated human naïve CD8+ T cells down-modulate the CD8β chain and become CD8αα T cells
Authors: Esgalhado André J. , Reste-Ferreira Débora , Weinhold Sandra , Uhrberg Markus , Cardoso Elsa M. , Arosa Fernando A.
Published: June 2024

Antigen-driven human effector-memory CD8+ T cells expressing low levels of the CD8β chain have been previously described. However, little is known on a possible antigen-independent trigger. We have examined the impact that IL-15 has on the expression of CD8β on purified human naïve CD8+ T cells after CFSE labeling and culture with IL-15. As expected, IL-15 induced naïve CD8+ T cells to proliferate and differentiate. Remarkably, the process was associated with a cell-cycle dependent down-modulation of CD8β from the cell surface, leading to the generation of CD8αβlow and CD8αβ− (i.e., CD8αα) T cells. In contrast, expression of the CD8α chain remained steady or even increased. Neither IL-2 nor IL-7 reproduced the effect of IL-15. Determination of mRNA levels for CD8α and CD8β isoforms by qPCR revealed that IL-15 promoted a significant decrease in mRNA levels of the CD8β M-4 isoform, while levels of the M-1/M-2 isoforms and of CD8α increased. Noteworthy, CD8+ T cell blasts obtained after culture of CD8+ T cells with IL-15 showed a cell-cycle dependent increase in the level of the tyrosine kinase Lck, when compared to CD8+ T cells at day 0. This study has shown for the first time that IL-15 generates CD8αα+αβlow and CD8αα+αβ− T cells containing high levels of Lck, suggesting that they may be endowed with unique functional features.
Heart immunoengineering by lentiviral vector-mediated genetic modification during normothermic ex vivo perfusion
Authors: Schmalkuche Katharina , Rother Tamina , Burgmann Jonathan M. , Voß Henrike , Höffler Klaus , Dogan Günes , Ruhparwar Arjang , Schmitto Jan D. , Blasczyk Rainer , Figueiredo Constanca
Published: June 2024

Heart transplantation is associated with major hurdles, including the limited number of available organs for transplantation, the risk of rejection due to genetic discrepancies, and the burden of immunosuppression. In this study, we demonstrated the feasibility of permanent genetic engineering of the heart during ex vivo perfusion. Lentiviral vectors encoding for short hairpin RNAs targeting beta2-microglobulin (shβ2m) and class II transactivator (shCIITA) were delivered to the graft during two hours of normothermic EVHP. Highly efficient genetic engineering was indicated by stable reporter gene expression in endothelial cells and cardiomyocytes. Remarkably, swine leucocyte antigen (SLA) class I and SLA class II expression levels were decreased by 66% and 76%, respectively, in the vascular endothelium. Evaluation of lactate, troponin T, and LDH levels in the perfusate and histological analysis showed no additional cell injury or tissue damage caused by lentiviral vectors. Moreover, cytokine secretion profiles (IL-6, IL-8, and TNF-α) of non-transduced and lentiviral vector-transduced hearts were comparable. This study demonstrated the ex vivo generation of genetically engineered hearts without compromising tissue integrity. Downregulation of SLA expression may contribute to reduce the immunogenicity of the heart and support graft survival after allogeneic or xenogeneic transplantation.
Pneumococcal hydrogen peroxide regulates host cell kinase activity
Authors: Bazant Jasmin , Weiss Astrid , Baldauf Julia , Schermuly Ralph Theo , Hain Torsten , Lucas Rudolf , Mraheil Mobarak Abu
Published: June 2024

Introduction

Protein kinases are indispensable reversible molecular switches that adapt and control protein functions during cellular processes requiring rapid responses to internal and external events. Bacterial infections can affect kinase-mediated phosphorylation events, with consequences for both innate and adaptive immunity, through regulation of antigen presentation, pathogen recognition, cell invasiveness and phagocytosis. Streptococcus pneumoniae (Spn), a human respiratory tract pathogen and a major cause of community-acquired pneumoniae, affects phosphorylation-based signalling of several kinases, but the pneumococcal mediator(s) involved in this process remain elusive. In this study, we investigated the influence of pneumococcal H2O2 on the protein kinase activity of the human lung epithelial H441 cell line, a generally accepted model of alveolar epithelial cells.

Methods

We performed kinome analysis using PamGene microarray chips and protein analysis in Western blotting in H441 lung cells infected with Spn wild type (SpnWT) or with SpnΔlctOΔspxB -a deletion mutant strongly attenuated in H2O2 production- to assess the impact of pneumococcal hydrogen peroxide (H2O2) on global protein kinase activity profiles.

Results

Our kinome analysis provides direct evidence that kinase activity profiles in infected H441 cells significantly vary according to the levels of pneumococcal H2O2. A large number of kinases in H441 cells infected with SpnWT are significantly downregulated, whereas this no longer occurs in cells infected with the mutant SpnΔlctOΔspxB strain, which lacks H2O2. In particular, we describe for the first time H2O2-mediated downregulation of Protein kinase B (Akt1) and activation of lymphocyte-specific tyrosine protein kinase (Lck) via H2O2-mediated phosphorylation.
Machine learning based prediction models for analyzing risk factors in patients with acute abdominal pain: a retrospective study
Authors: Gan Tian , Liu Xiaochao , Liu Rong , Huang Jing , Liu Dingxi , Tu Wenfei , Song Jiao , Cai Pengli , Shen Hexiao , Wang Wei
Published: June 2024

Background

Acute abdominal pain (AAP) is a common symptom presented in the emergency department (ED), and it is crucial to have objective and accurate triage. This study aims to develop a machine learning-based prediction model for AAP triage. The goal is to identify triage indicators for critically ill patients and ensure the prompt availability of diagnostic and treatment resources.

Methods

In this study, we conducted a retrospective analysis of the medical records of patients admitted to the ED of Wuhan Puren Hospital with acute abdominal pain in 2019. To identify high-risk factors, univariate and multivariate logistic regression analyses were used with thirty-one predictor variables. Evaluation of eight machine learning triage prediction models was conducted using both test and validation cohorts to optimize the AAP triage prediction model.

Results

Eleven clinical indicators with statistical significance (p < 0.05) were identified, and they were found to be associated with the severity of acute abdominal pain. Among the eight machine learning models constructed from the training and test cohorts, the model based on the artificial neural network (ANN) demonstrated the best performance, achieving an accuracy of 0.9792 and an area under the curve (AUC) of 0.9972. Further optimization results indicate that the AUC value of the ANN model could reach 0.9832 by incorporating only seven variables: history of diabetes, history of stroke, pulse, blood pressure, pale appearance, bowel sounds, and location of the pain.

Conclusion

The ANN model is the most effective in predicting the triage of AAP. Furthermore, when only seven variables are considered, including history of diabetes, etc., the model still shows good predictive performance. This is helpful for the rapid clinical triage of AAP patients and the allocation of medical resources.
Establishment of the uterine microbiome following artificial insemination in virgin heifers
Authors: Moraes Joao G. N. , Gull Tamara , Ericsson Aaron C. , Poock Scott E. , Caldeira Monica O. , Lucy Matthew C.
Published: June 2024

Introduction

The concept of a sterile uterus was challenged by recent studies that have described the microbiome of the virgin and pregnant uterus for species including humans and cattle. We designed two studies that tested whether the microbiome is introduced into the uterus when the virgin heifer is first inseminated and whether the origin of the microbiome is the vagina/cervix.

Methods

The uterine microbiome was measured immediately before and after an artificial insemination (AI; Study 1; n = 7 AI and n = 6 control) and 14 d after insemination (Study 2; n = 12 AI and n = 12 control) in AI and non-AI (control) Holstein heifers. A third study (Study 3; n = 5 Holstein heifers) that included additional negative controls was subsequently conducted to support the presence of a unique microbiome within the uterus despite the low microbial biomass and regardless of insemination. Traditional bacteriological culture was performed in addition to 16S rRNA gene sequencing on the same samples to determine whether there were viable organisms in addition to those detected based on DNA sequencing (16S rRNA gene sequence).

Results and discussion

Inseminating a heifer did not lead to a large change in the microbiome when assessed by traditional methods of bacterial culture or metataxonomic (16S rRNA gene) sequencing (results of Studies 1 and 2). Very few bacteria were cultured from the body or horn of the uterus regardless of whether an AI was or was not (negative control) performed. The cultured bacterial genera (e.g., Bacillus, Corynebacterium, Cutibacterium, Micrococcus, Staphylococcus, and Streptococcus) were typical of those found in the soil, environment, skin, mucous membranes, and urogenital tract of animals. Metataxonomic sequencing of 16S rRNA gene generated a large number of amplicon sequence variants (ASV), but these larger datasets that were based on DNA sequencing did not consistently demonstrate an effect of AI on the abundance of ASVs across all uterine locations compared with the external surface of the tract (e.g., perimetrium; positive control samples for environment contamination during slaughter and collection). Major genera identified by 16S rRNA gene sequencing overlapped with those identified with bacterial culture and included Cutibacterium, Staphylococcus, and Streptococcus.
Differential effects of allopregnanolone and diazepam on social behavior through modulation of neural oscillation dynamics in basolateral amygdala and medial prefrontal cortex
Authors: Yawata Yosuke , Tashima Ryoichi , Aritomi Hiroyuki , Shimada Shinji , Onodera Tsukasa , Taishi Teruhiko , Takasu Keiko , Ogawa Koichi
Published: June 2024

Effective treatments for major depressive disorder (MDD) have long been needed. One hypothesis for the mechanism of depression involves a decrease in neuroactive steroids such as allopregnanolone, an endogenous positive allosteric modulator of the γ-aminobutyric acid–gated chloride channel (GABAA) receptor. In our previous study, we discovered that allopregnanolone, not diazepam, exhibited antidepressant-like effects in the social interaction test (SIT) of social defeat stress (SDS) model mice. However, the dynamics of neuronal activity underlying the antidepressant-like effect remain unknown. In the current study, we conducted local field potentials (LFPs) recordings from the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) during the SIT to elucidate the relationship between the antidepressant-like effect and neuronal oscillation. We discovered that allopregnanolone has antidepressant-like effects in the SIT of SDS model mice by decreasing intervals of repetitive social interaction (inter-event intervals), resulting in increase of total social interaction time. We also found that theta and beta oscillation increased in BLA at the onset of social interaction following administration of allopregnanolone, which differed from the effects of diazepam. Theta and beta power in BLA within the social interaction zone exhibited a positive correlation with interaction time. This increase of theta and beta power was negatively correlated with inter-event intervals. Regarding theta-band coordinated activity between the BLA and mPFC, theta power correlation decreased at the onset of social interaction with the administration of allopregnanolone. These findings suggest that theta activity in BLA following social interaction and the reduced theta-band coordinated activity between the BLA and mPFC are implicated in social interaction, which is one of the antidepressant behaviors. These differences in neural activity could elucidate the distinctive mechanism underlying antidepressant-like effects of neuroactive steroids, as opposed to benzodiazepines.
Preserved VPS13A distribution and expression in Huntington’s disease: divergent mechanisms of action for similar movement disorders?
Authors: García-García Esther , Carreras-Caballé Maria , Coll-Manzano Albert , Ramón-Lainez Alba , Besa-Selva Gisela , Pérez-Navarro Esther , Malagelada Cristina , Alberch Jordi , Masana Mercè , Rodríguez Manuel J.
Published: June 2024

VPS13A disease and Huntington’s disease (HD) are two basal ganglia disorders that may be difficult to distinguish clinically because they have similar symptoms, neuropathological features, and cellular dysfunctions with selective degeneration of the medium spiny neurons of the striatum. However, their etiology is different. VPS13A disease is caused by a mutation in the VPS13A gene leading to a lack of protein in the cells, while HD is due to an expansion of CAG repeat in the huntingtin (Htt) gene, leading to aberrant accumulation of mutant Htt. Considering the similarities of both diseases regarding the selective degeneration of striatal medium spiny neurons, the involvement of VPS13A in the molecular mechanisms of HD pathophysiology cannot be discarded. We analyzed the VPS13A distribution in the striatum, cortex, hippocampus, and cerebellum of a transgenic mouse model of HD. We also quantified the VPS13A levels in the human cortex and putamen nucleus; and compared data on mutant Htt-induced changes in VPS13A expression from differential expression datasets. We found that VPS13A brain distribution or expression was unaltered in most situations with a decrease in the putamen of HD patients and small mRNA changes in the striatum and cerebellum of HD mice. We concluded that the selective susceptibility of the striatum in VPS13A disease and HD may be a consequence of disturbances in different cellular processes with convergent molecular mechanisms already to be elucidated.
What was the global burden of kidney cancer attributable to high body mass index from 1990 to 2019? There existed some points noteworthy
Authors: Yao Xue , Luo Xiao-yan , Tai Yang-hao , Wang Kang , Shang Ji-wen
Published: June 2024

Purpose

With the prevalence of high body mass index (HBMI) increasing over the past 30 years, it is essential to examine the impact of obesity on kidney cancer. This study aims to explore the attributable burden of kidney cancer associated with HBMI and its proportion at different levels.

Methods and materials

The data used in this research were obtained from the Global Burden of Diseases Study 2019. We utilized DisMod-MR 2.1, a Bayesian meta-regression tool, to estimate the burden of kidney cancer attributable to HBMI, which was measured by age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR). Correlation analysis was conducted by the Spearman rank order correlation method. The temporal trends were analyzed by estimating the estimated annual percentage change (EAPC).

Results

Globally in 2019, there were a total of 31.7 thousand deaths and 751.89 thousand disability-adjusted life years (DALYs) attributable to kidney cancer caused by HBMI, increased by 183.1 and 164%, respectively. Over the period from 1990 to 2019, the burden of kidney cancer attributable to HBMI increased in all regions, with the most significant increases occurring in Low-middle socio-demographic index (SDI) and Low SDI regions. At the national level, countries with lower SDI had lower ASMR and ASDR compared to developed nations. However, the EAPC values, which indicate the rate of increase, were significantly higher in these countries than in developed nations. Furthermore, across all years from 1990 to 2019, males experienced a greater and more rapidly increasing burden of kidney cancer attributable to HBMI than females.

Conclusion

As the population grows and dietary patterns shift, the burden of kidney cancer attributable to HBMI is expected to become even more severe. Males and developed regions have borne a heavier burden from 1990 to 2019. However, the EAPC values for both ASMR and ASDR were higher in males but not in regions with higher SDI values.
Inhibitory effects of cassiae semen extract on the formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) in model system
Authors: Yu Di , Li Youyou , Jiang Donghua , Kong Fanlei
Published: June 2024

Introduction

2-Amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP), a heterocyclic amine (HAA), is found in meat products heated at high temperatures. However, PhIP is a mutagenic and potential carcinogenic compound. Cassiae semen, a type of medicine and food homology plant, is abundant in China and has been less applied for inhibiting heterocyclic amines.

Methods

To investigate the inhibitory effect of cassiae semen extract on PhIP formation within a model system and elucidate the inhibitory mechanism, an ultrasonic-assisted method with 70% ethanol was used to obtain cassiae semen extract, which was added to a model system (0.6 mmol of phenylalanine: creatinine, 1:1). PhIP was analyzed by LC–MS to determine inhibitory effect. The byproducts of the system and the mechanism of PhIP inhibition were verified by adding the extract to a model mixture of phenylacetaldehyde, phenylacetaldehyde and creatinine.

Results

The results indicated that PhIP production decreased as the concentration of cassiae semen extract increased, and the highest inhibition rate was 91.9%. Byproduct (E), with a mass–charge ratio of m/z 199.9, was detected in the phenylalanine and creatinine model system but was not detected in the other systems. The cassiae semen extract may have reacted with phenylalanine to produce byproduct (E), which prevented the degradation of phenylalanine by the Strecker reaction to produce phenylacetaldehyde.

Discussion

Cassiae semen extract consumed phenylalanine, which is the precursor for PhIP, thus inhibiting the formation of phenylacetaldehyde and ultimately inhibiting PhIP formation. The main objective of this study was to elucidate the mechanism by which cassiae semen inhibit PhIP formation and establish a theoretical and scientific foundation for practical control measures.
Case report: Cervical brachytherapy technique for locally advanced cervical cancer in a patient with complete bicorporeal uterus
Authors: Ding Lipeng , Zheng Zhangcai , Cao Yueao , Wang Zhenjiang , Zhu Baoyu , Miao Guoying , Yuan Wenzhen
Published: June 2024

Purpose

The purpose of this study was to describe an approach to cervical brachytherapy for a patient with a complete bicorporeal uterus and locally advanced cervical cancer (LACC).

Materials and methods

The patient was a 53-year-old woman with a complete bicorporeal uterus, diagnosed with stage IIB cervical squamous cell carcinoma due to contact bleeding. The patient underwent concurrent chemoradiotherapy (CCRT), external beam pelvic radiotherapy with 45 Gy/25 fractions, and weekly cisplatin (40 mg/m2). Brachytherapy was administered following the completion of external beam radiotherapy.

Results

The brachytherapy, which was CT (Computed Tomography)-guided using two CT-compatible tandems and two CT-compatible ovoids, delivered a prescription dose of HRCTV D90 was 6 Gy*5F, which achieved satisfactory dose coverage. The patient’s final HRCTV D90 EQD210 was 84.9 Gy, and IRCTV D90 EQD210 was 63.5 Gy. Rectum D2cc EQD23 was 66.03 Gy, bladder D2cc EQD23 was 75.57 Gy, sigmoid D2cc EQD23 was 63.93 Gy, and intestine D2cc EQD23 was 65.86 Gy. Follow-up at 1 year was CR.

Conclusions

For patients with cervical cancer and a complete bicorporeal uterus, using double tandems combined with double ovoids is a feasible treatment method to ensure adequate dose coverage without causing additional damage. This method is also applicable to patients with endometrial cancer.
Comparative effectiveness of antihypertensive monotherapies in primary prevention of cardiovascular events—a real-world longitudinal inception cohort study
Authors: Li Xuechun , Bijlsma Maarten J. , de Vos Stijn , Bos Jens H. J. , Mubarik Sumaira , Schuiling-Veninga Catharina C. M. , Hak Eelko
Published: June 2024

Introduction

Antihypertensive drugs are used preventatively to lower the risk of cardiovascular disease events. Comparative effectiveness studies on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and thiazides have yielded inconsistent results and given little consideration to patient adherence. Using a longitudinal cohort and considering time-varying adherence and confounding factors, we aimed to estimate the real-world effectiveness of five major antihypertensive drug monotherapies in the primary prevention of cardiovascular events.

Methods

Eligible patients for a retrospective inception cohort study were selected using information obtained from the University of Groningen IADB.nl pharmacy prescription database. Cohort 1 comprised adherent patients with a follow-up time exceeding 1 year, and cohort 2 comprised all patients independent of adherence. The exposures were ACEIs, ARBs, BBs, CCBs, and thiazides. The primary outcome was the time to the first prescription for an acute cardiac drug therapy (CDT) measured using valid drug proxies to identify the first major cardiovascular event. A per-protocol analytical approach was adopted with inverse probability of treatment weighted (IPTW), time-varying Cox regression analysis to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

In cohort 1 (n = 22,441), 1,294 patients (5.8%) were prescribed an acute CDT with an average follow-up time of 4.2 ± 2.8 years. Following IPTW, the hazard measures of ARBs and thiazides were lower than those of BBs (HRs: 0.79 and 0.80, respectively; 95% CIs: 0.64–0.97 and 0.69–0.94, respectively). Among drug-treated diabetic patients, the hazard measures were even lower, with HR point estimates of 0.43 (CI: 0.19–0.98) for ARBs and 0.32 (CI: 0.13–0.82) for thiazides. In cohort 2 (n = 33,427) and sensitivity analysis, the comparative effectiveness results for thiazides and BBs were similar to those for cohort 1.

Conclusion

The findings of this real-world analysis suggest that the incidence of CDT associated with long-term thiazide or ARB monotherapy is lower than the incidence of CDT with BBs, notably among high-risk patients. Incidences of CDT associated with ACEIs and CCBs were comparable relative to those associated with BBs.
Polygonatum cyrtonema polysaccharides reshape the gut microbiota to ameliorate dextran sodium sulfate-induced ulcerative colitis in mice
Authors: Lin Chaoyou , Song Dawei , Wang Shangwen , Chu Yunfei , Chi Changxing , Jia Sining , Lin Mengyi , He Chenbei , Jiang Chengxi , Gong Fanghua , Chen Qiongzhen
Published: June 2024

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized inflammatory imbalance, intestinal epithelial mucosal damage, and dysbiosis of the gut microbiota. Polygonatum cyrtonema polysaccharides (PCPs) can regulate gut microbiota and inflammation. Here, the different doses of PCPs were administered to dextran sodium sulfate-induced UC mice, and the effects of the whole PCPs were compared with those of the fractionated fractions PCP-1 (19.9 kDa) and PCP-2 (71.6 and 4.2 kDa). Additionally, an antibiotic cocktail was administered to UC mice to deplete the gut microbiota, and PCPs were subsequently administered to elucidate the potential role of the gut microbiota in these mice. The results revealed that PCP treatment significantly optimized the lost weight and shortened colon, restored the balance of inflammation, mitigated oxidative stress, and restored intestinal epithelial mucosal damage. And, the PCPs exhibited superior efficacy in ameliorating these symptoms compared with PCP-1 and PCP-2. However, depletion of the gut microbiota diminished the therapeutic effects of PCPs in UC mice. Furthermore, fecal transplantation from PCP-treated UC mice to new UC-afflicted mice produced therapeutic effects similar to PCP treatment. So, PCPs significantly ameliorated the symptoms, inflammation, oxidative stress, and intestinal mucosal damage in UC mice, and gut microbiota partially mediated these effects.
A systems genomics and genetics approach to identify the genetic regulatory network for lignin content in Brassica napus seeds
Authors: Zhang Wentao , Higgins Erin E. , Robinson Stephen J. , Clarke Wayne E. , Boyle Kerry , Sharpe Andrew G. , Fobert Pierre R. , Parkin Isobel A. P.
Published: June 2024

Seed quality traits of oilseed rape, Brassica napus (B. napus), exhibit quantitative inheritance determined by its genetic makeup and the environment via the mediation of a complex genetic architecture of hundreds to thousands of genes. Thus, instead of single gene analysis, network-based systems genomics and genetics approaches that combine genotype, phenotype, and molecular phenotypes offer a promising alternative to uncover this complex genetic architecture. In the current study, systems genetics approaches were used to explore the genetic regulation of lignin traits in B. napus seeds. Four QTL (qLignin_A09_1, qLignin_A09_2, qLignin_A09_3, and qLignin_C08) distributed on two chromosomes were identified for lignin content. The qLignin_A09_2 and qLignin_C08 loci were homologous QTL from the A and C subgenomes, respectively. Genome-wide gene regulatory network analysis identified eighty-three subnetworks (or modules); and three modules with 910 genes in total, were associated with lignin content, which was confirmed by network QTL analysis. eQTL (expression quantitative trait loci) analysis revealed four cis-eQTL genes including lignin and flavonoid pathway genes, cinnamoyl-CoA-reductase (CCR1), and TRANSPARENT TESTA genes TT4, TT6, TT8, as causal genes. The findings validated the power of systems genetics to identify causal regulatory networks and genes underlying complex traits. Moreover, this information may enable the research community to explore new breeding strategies, such as network selection or gene engineering, to rewire networks to develop climate resilience crops with better seed quality.
Parental depression moderates the relationship between childhood maltreatment and the recognition of children expressions of emotions
Authors: Bérubé Annie , Pétrin Rachel , Blais Caroline
Published: June 2024

Background

Sensitivity plays a crucial role in parenting as it involves the ability to perceive and respond appropriately to children’s signals. Childhood maltreatment and depression can negatively impact adults’ ability to recognize emotions, but it is unclear which of these factors has a greater impact or how they interact. This knowledge is central to developing efficient, targeted interventions. This paper examines the interaction between parents’ depressive symptoms and childhood maltreatment and its influence on their ability to recognize the five basic emotions (happiness, anger, sadness, fear, and disgust) in children’s faces.

Method

The sample consisted of 52 parents. Depressive symptoms were measured by the depression subscale of the Brief Symptom Inventory-18 (BSI-18), and maltreatment history was assessed by the Childhood Trauma Questionnaire (CTQ). Children’s emotional stimuli were morphed images created using The Child Affective Facial Expression (CAFE) database.

Results

Our findings indicate that depressive symptoms moderate the relationship between parents’ history of childhood maltreatment and emotion recognition skills. Parents with higher depressive symptoms had lower emotion recognition accuracy when they had not experienced maltreatment. When childhood maltreatment was severe, emotion recognition skills were more consistent across all levels of depression. The relationship between depression and emotion recognition was primarily linked to recognizing sadness in children’s faces.

Conclusion

These findings highlight how different experiences can affect parental abilities in emotion recognition and emphasize the need for interventions tailored to individual profiles to improve their effectiveness.
Regional differences in heart failure risk in the United Kingdom are partially explained by biological aging
Authors: Wong Jason Y. Y. , Blechter Batel , Rodriquez Erik J. , Shearer Joseph J. , Breeze Charles , Pérez-Stable Eliseo J. , Roger Véronique L.
Published: June 2024

Background

Heart failure (HF) risk is greater in rural versus urban regions in the United States (US), potentially due to differences in healthcare coverage and access. Whether this excess risk applies to countries with universal healthcare is unclear and the underlying biological mechanisms are unknown. In the prospective United Kingdom (UK) Biobank, we investigated urban–rural regional differences in HF risk and the mechanistic role of biological aging.

Methods

Multivariable Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HF in relation to residential urban–rural region and a Biological Health Score (BHS) that reflects biological aging from environmental, social, or dietary stressors. We estimated the proportion of the total effect of urban–rural region on HF mediated through BHS.

Results

Among 417,441 European participants, 10,332 incident HF cases were diagnosed during the follow-up. Compared to participants in large urban regions of Scotland, those in England/Wales had significantly increased HF risk (smaller urban: HR = 1.83, 95%CI: 1.64–2.03; suburban: HR = 1.77, 95%CI: 1.56–2.01; very rural: HR = 1.61, 95%CI: 1.39–1.85). Additionally, we found a dose–response relationship between increased biological aging and HF risk (HRper 1 SD increase = 1.14 (95%CI: 1.12–1.17). Increased biological aging mediated a notable 6.6% (p < 0.001) of the total effect of urban–rural region on HF.

Conclusion

Despite universal healthcare in the UK, disparities in HF risk by region were observed and may be partly explained by environmental, social, or dietary factors related to biological aging. Our study contributes to precision public health by informing potential biological targets for intervention.
The influence of the national drug price negotiation policy reform on the medical expenses of patients in Xuzhou City: an interrupted time series analysis
Authors: Qin Zhaohui , He Meng , Shen Huangying , Liu Sha , Xu Shuo , Chen Lijiang
Published: June 2024

Background

To reduce the burden of patients’ medical care, the Xuzhou Municipal Government has initiated an exploratory study on the supply model and categorized management of nationally negotiated drugs. This study aims to understand the extent to which Xuzhou’s 2021 reform of the National Drug Price Negotiation (NDPN) policy has had a positive impact on the healthcare costs of individuals with different types of health insurance.

Methods

The Interrupted Time Series Analysis method was adopted, and the changes in average medical expenses per patient, average medical insurance payment cost per patient and actual reimbursement ratio were investigated by using the data of single-drug payments in Xuzhou from October 2020 to October 2022.

Results

Following the implementation of the policy, there was a significant decrease in the average medical expenses per patient of national drug negotiation in Xuzhou, with a reduction of 62.42 yuan per month (p < 0.001). Additionally, the average medical insurance payment cost per patient decreased by 44.13 yuan per month (p = 0.01). Furthermore, the average medical expenses per patient of urban and rural medical insurance participants decreased by 63.45 yuan (p < 0.001), and the average monthly medical insurance payment cost per patient decreased by 57.56 yuan (p < 0.04). However, the mean total medical expenditures for individuals enrolled in employee medical insurance decreased by 63.41 yuan per month (p < 0.001), whereas the monthly decrease was 22.11 yuan per month (p = 0.21). On the other hand, there was no discernible change in the actual reimbursement ratio.

Conclusion

After the adoption of the NDPN policy, a noticeable decline has been observed in the average medical expenses per patient and the mean cost of the average medical insurance payment per patient, although to a limited extent. Notably, the reduction in employee medical insurance surpasses that of urban and rural medical insurance.
Trends in admission rates of primary angle closure diseases for the urban population in China, 2011–2021
Authors: Chen Qi , Shen Peng , Zhou Mengtian , Cao Yang , Zheng Xuanli , Zhao Fengping , Lin Haishuang , Ding Yutong , Ji Yiting , Zuo Jingjing , Lin Hongbo , Liang Yuanbo
Published: June 2024

Background

Cataract surgery and laser peripheral iridotomy (LPI) are effective approaches for preventing primary angle closure diseases (PACDs), as well as acute primary angle closure (APAC). Due to the development of population screening and increases in cataract surgery rates, this study aimed to examine trends in the admission rates of PACD among the urban population in China.

Methods

This cross-sectional study examined patients who were admitted to a hospital for PACD, and who underwent cataract surgery or LPI operations. The data were obtained from the Yinzhou Regional Health Information Platform (YRHIP) from 2011 to 2021. The annual rates of PACD and APAC admissions, cataract surgery and LPI were analyzed, with the number of cases used as numerators and the annual resident population in Yinzhou district used as denominators.

Results

A total of 2,979 patients with PACD admissions, 1,023 patients with APAC admissions, 53,635 patients who underwent cataract surgery and 16,450 patients who underwent LPI were included. The number of annual admissions for PACD gradually increased from 22 cases (1.6/100000) in 2011 to 387 cases (30.8/100000) in 2016, after which it decreased to 232 cases (16.2/100000) in 2019 and then increased to 505 cases (30.6/100000) in 2021. The number of cataract surgeries gradually increased from 1728 (127.7/100000) in 2011 to 7002 (424.9/100000) in 2021. Similarly, the number of LPI gradually increased from 109 (8.0/100000) in 2011 to 3704 (224.8/100000) in 2021.

Conclusion

The admission rates of PACD for the urban population in China have declined in recent years after a long increasing trend in the rates of cataract surgery and LPI. However, it increased rapidly during the COVID-19 epidemic. The national health database should be further utilized to investigate temporal trends in the prevalence of PACD.