bluuebunny/crossref_metadata_2025 huggingface dataset:
jmBIG: enhancing dynamic risk prediction and personalized medicine through joint modeling of longitudinal and survival data in big routinely collected data
Authors: Bhattacharjee Atanu , Rajbongshi Bhrigu Kumar , Vishwakarma Gajendra K.
Published: August 2024

We have introduced the R package jmBIG to facilitate the analysis of large healthcare datasets and the development of predictive models. This package provides a comprehensive set of tools and functions specifically designed for the joint modelling of longitudinal and survival data in the context of big data analytics. The jmBIG package offers efficient and scalable implementations of joint modelling algorithms, allowing for integrating large-scale healthcare datasets.

By utilizing the capabilities of jmBIG, researchers and analysts can effectively handle the challenges associated with big healthcare data, such as high dimensionality and complex relationships between multiple outcomes.

With the support of jmBIG, analysts can seamlessly fit Bayesian joint models, generate predictions, and evaluate the performance of the models. The package incorporates cutting-edge methodologies and harnesses the computational capabilities of parallel computing to accelerate the analysis of large-scale healthcare datasets significantly. In summary, jmBIG empowers researchers to gain deeper insights into disease progression and treatment response, fostering evidence-based decision-making and paving the way for personalized healthcare interventions that can positively impact patient outcomes on a larger scale.
Development of prognostic model incorporating a ferroptosis/cuproptosis-related signature and mutational landscape analysis in muscle-invasive bladder cancer
Authors: Hao Sida , Yang Zitong , Wang Gang , Cai Guofeng , Qin Yong
Published: August 2024

Background

Muscle-invasive bladder cancer (MIBC) is a prevalent and aggressive malignancy. Ferroptosis and cuproptosis are recently discovered forms of programmed cell death (PCD) that have attracted much attention. However, their interactions and impacts on MIBC overall survival (OS) and treatment outcomes remain unclear.

Methods

Data from the TCGA-BLCA project (as the training set), cBioPortal database, and GEO datasets (GSE13507 and GSE32894, as the test sets) were utilized to identify hub ferroptosis/cuproptosis-related genes (FRGs and CRGs) and develop a prognostic signature. Differential expression analysis (DEA) was conducted, followed by univariate and multivariate Cox’s regression analyses and multiple machine learning (ML) techniques to select genetic features. The performance of the ferroptosis/cuproptosis-related signature was evaluated using Kaplan–Meier (K–M) survival analysis and receiver-operating characteristics (ROC) curves. Mutational and tumour immune microenvironment landscapes were also explored. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) experiments confirmed the expression patterns of the hub genes, and functional assays assessed the effects of SCD knockdown on cell viability, proliferation, and migration.

Results

DEA revealed dysregulated FRGs and CRGs in the TCGA MIBC cohort. SCD, DDR2, and MT1A were identified as hub genes. A prognostic signature based on the sum of the weighted expression of these genes demonstrated strong predictive efficacy in the training and test sets. Nomogram incorporating this signature accurately predicted 1-, 3-, and 5-year survival probabilities in the TCGA cohort and GSE13507 dataset. Copy number variation (CNV) and tumour immune microenvironment analysis revealed that high risk score level groups were associated with immunosuppression and lower tumour purity. The associations of risk scores with immunotherapy and chemical drugs were also explored, indicating their potential for guiding treatment for MIBC patients. The dysregulated expression patterns of three hub genes were validated by RT-qPCR experiments.

Conclusions

Targeting hub FRGs and CRGs could be a promising therapeutic approach for MIBC. Our prognostic model offers a new framework for MIBC subtyping and can inform personalized therapeutic strategies.
Sex and population differences in the cardiometabolic continuum: a machine learning study using the UK Biobank and ELSA-Brasil cohorts
Authors: Paula Daniela Polessa , Camacho Marina , Barbosa Odaleia , Marques Larissa , Harter Griep Rosane , da Fonseca Maria Jesus Mendes , Barreto Sandhi , Lekadir Karim
Published: August 2024

Background

The temporal relationships across cardiometabolic diseases (CMDs) were recently conceptualized as the cardiometabolic continuum (CMC), sequence of cardiovascular events that stem from gene-environmental interactions, unhealthy lifestyle influences, and metabolic diseases such as diabetes, and hypertension. While the physiological pathways linking metabolic and cardiovascular diseases have been investigated, the study of the sex and population differences in the CMC have still not been described.

Methods

We present a machine learning approach to model the CMC and investigate sex and population differences in two distinct cohorts: the UK Biobank (17,700 participants) and the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) (7162 participants). We consider the following CMDs: hypertension (Hyp), diabetes (DM), heart diseases (HD: angina, myocardial infarction, or heart failure), and stroke (STK). For the identification of the CMC patterns, individual trajectories with the time of disease occurrence were clustered using k-means. Based on clinical, sociodemographic, and lifestyle characteristics, we built multiclass random forest classifiers and used the SHAP methodology to evaluate feature importance.

Results

Five CMC patterns were identified across both sexes and cohorts: EarlyHyp, FirstDM, FirstHD, Healthy, and LateHyp, named according to prevalence and disease occurrence time that depicted around 95%, 78%, 75%, 88% and 99% of individuals, respectively. Within the UK Biobank, more women were classified in the Healthy cluster and more men in all others. In the EarlyHyp and LateHyp clusters, isolated hypertension occurred earlier among women. Smoking habits and education had high importance and clear directionality for both sexes. For ELSA-Brasil, more men were classified in the Healthy cluster and more women in the FirstDM. The diabetes occurrence time when followed by hypertension was lower among women. Education and ethnicity had high importance and clear directionality for women, while for men these features were smoking, alcohol, and coffee consumption.

Conclusions

There are clear sex differences in the CMC that varied across the UK and Brazilian cohorts. In particular, disadvantages regarding incidence and the time to onset of diseases were more pronounced in Brazil, against woman. The results show the need to strengthen public health policies to prevent and control the time course of CMD, with an emphasis on women.
Assessment of the unwanted tooth movement associated with an extended maxillary fixed retainer (3D analysis)
Authors: Abbas Mohamed H. , Abdalla Essam M. , Marzouk Eiman S. , Harouni Nadia M. El
Published: August 2024

Background

Posttreatment changes after orthodontic treatment are challenging. One of the main reasons for such a phenomenon is the lack of patient compliance with removable retainers especially in the maxillary arch, due to palatal coverage, deterioration of speech, decreased masticatory efficiency, and loss of retainers. Fixed retainers have been introduced to overcome patient compliance and provide longer stable results. However, teeth still show movements when a six-unit fixed retainer is in place. Thus, in this study, an eight-unit fixed retainer was evaluated in an attempt to eliminate unwanted movements.

The aim of this research

was to assess short-term positional changes associated with an eight-unit extended maxillary fixed retainer.

Materials and methods

A single-arm clinical trial was conducted to address the aim of the study. This research was approved by the institutional review board of the Faculty of Dentistry, Alexandria University (IORG:0008839, No-0479–8/2022). The registration date of this study was 5/06/2023. Twenty-eight patients (19.8 ± 4.5 years) who had finished the active orthodontic phase and started retention had an eight-unit extended maxillary fixed retainer that was bonded to the palatal surface of the maxillary incisors, canines, and the first premolars or the second premolars. Pre-retention and one-year post-retention intra-oral scans were made to produce STL files that were superimposed to determine the amount of tooth change. Additionally, analysis of digital casts and lateral cephalometric radiographs was performed.

Results

Statistically significant changes in all planes and the rotation of teeth after one year of retention were found. The upper right lateral incisor exhibited the most evident change in the vertical plane, while the upper right central incisor exhibited the greatest change overall. Minimal changes in the cast measurements were observed. Lateral cephalometric measurements showed minimal changes after one year of retention, and these changes were not statistically significant except in the interincisal angle and the angle between the upper incisor and the line connecting the A-point to the pogonion.

Conclusion

Increasing the extension of maxillary fixed retainers did not eliminate unwanted tooth movement in the first year of retention.
Addressing musculoskeletal curricular inadequacies within undergraduate medical education
Authors: Peeler Jason
Published: August 2024

Background

Musculoskeletal (MSK) injuries and diseases place a significant burden on the health care system. Despite this, research indicates that physician training in the area of MSK medicine has historically been inadequate, with a majority of medical students feeling that their training in MSK medicine is lacking. The goal of this investigation was to evaluate the efficacy of a new preclinical MSK curriculum that was implemented within a nationally accredited allopathic medical program.

Methods

Retrospective analysis was completed on five consecutive years (2017–2021) of preclinical MSK curricular data for 549 medical students, including mid and end-of-course examinations and end-of-course student satisfaction surveys. Both parametric and non-parametric methods of analysis were used to examine within and between class differences (P < 0.05).

Results

The new MSK curriculum covered 15 of 16 “core or must know” topics in MSK medicine, and academic performance was consistently high over the 5-year period of analysis (final course marks ranged from 76.6 ± 7.1 to 81.4 ± 8.1; failures/year: range from 0 to 4), being equal or above levels of student performance observed for other courses delivered during preclinical studies. Likert data from end-of-course surveys demonstrated that feedback was overwhelmingly positive (overall course satisfaction ranged from a low of 3.07/4.00 to a high of 3.56/4.00) and indicated that students felt that the new preclinical MSK curriculum did effectively support medical student learning and knowledge retention.

Conclusion

Results are expected to help advance the current body of knowledge that is dedicated to improving physician learning and knowledge retention in the area of MSK medicine and provides a curricular model that could be used by other nationally accredited medical programs to help enhance MSK learning at the preclinical levels of physician training.
Personalized care for complex lives: initial outcomes of a behaviorally-informed complex care intervention
Authors: Dolber Trygve , Muskin Ryan , Runnels Patrick
Published: August 2024

Background

5% of patients account for the majority of healthcare spend, but standardized interventions for this complex population struggle to generate return on investment. The aim of this study is the development and proof of concept of an adaptive intervention to reduce cost and risk of readmission for medically high-risk individuals with any behavioral health diagnosis.

Methods

A behaviorally-oriented, personalized care service was delivered using a consultative, team-based approach including a physician, counselor, dietitian and social worker in collaboration with nurse care coordinators. Iterative re-conceptualizations informed tailored treatment approaches to prevent acute decompensation while retraining behaviors that impeded recovery. This service was offered to a small set of members of the employee health plan at University Hospitals Cleveland with an existing behavioral health disorder from November of 2020 to March of 2023. 26 members receiving the service were identified and matched with 26 controls using a risk algorithm. Members and controls were then classified as high utilizers (n = 14) or standard utilizers (n = 38) based on utilization claims data.

Results

Primary outcomes of this study included medical expenditures (delineated as planned and unplanned spend) and readmission risk scores. Compared to risk-matched controls, both planned and unplanned health care expenditures significantly decreased (p < .05) for 7 high utilizers, and unplanned spend only significantly decreased for 19 standard utilizers (p < .05). Risk scores, which predict future spend, decreased significantly for standard utilizers (p < .05), but not for high utilizers.

Discussion

The value of a behaviorally-oriented personalized care intervention for medically high-risk patients in a commercial insurance population was demonstrated through decreased spend for high utilizers and decreased risk for standard utilizers. Further expansion, refinement, evaluation and scaling are warranted.
Fetal alcohol spectrum disorders prevention and clinical guidelines research - workshop report
Authors: Koehlmoos Tracey Pérez , Lee Elizabeth , Rivera Ilse , Wisdahl Jennifer , Erdman Katie , Donaldson Tom
Published: August 2024

It is estimated that up to 1 in 20 people in the United States may have a fetal alcohol spectrum disorder (FASD), or the array of physical, cognitive, emotional, and social disorders caused by exposure to alcohol during prenatal development (May et al., JAMA 319:474–82, 2018). While this condition is present in a broad range of individuals and families, it has not previously been examined in the military community, where cultural factors including an increased prevalence of alcohol misuse may pose a unique set of challenges (Health.mil, Alcohol misuse, 2024).

The Uniformed Services University of the Health Sciences (USUHS), in conjunction with FASD United, hosted the second annual Workshop on Fetal Alcohol Spectrum Disorders Prevention and Clinical Guidelines Research on 20 September 2023 in Washington, DC. Organized as part of a four-year, federally-funded health services research initiative on FASD in the U.S. Department of Defense (DoD) Military Health System (MHS), the workshop provided a forum for exploring the initiative’s focus and progress; examining current knowledge and practice in the research and clinical spheres; and identifying potential strategies to further improve prevention, screening, diagnosis, interventions, and family support. Building off of the 2022 workshop that covered the state of the science surrounding prenatal alcohol exposure and FASD, the 2023 focused primarily on FASD and efforts aimed at identification and management (Koehlmoos et al., BMC Proc 17 Suppl 12:19, 2023). One hundred and thirty attendees from academia, healthcare, federal agencies, and patient advocacy organizations gathered to share research findings; learn from lived experiences; and discuss initiatives to advance research, screening, and services for at-risk pregnant women as well as families and caregivers supporting individuals with FASD.
Multilevel medical insurance mitigate health cost inequality due to air pollution: Evidence from China
Authors: Wang Ennan , Zhu Minglai , Lin Yisha , Xi Xiaoyu
Published: August 2024

Background

Air pollution affects residents’ health to varying extents according to differences in socioeconomic status. However, there has been a lack of research on whether air pollution contributes to unfair health costs.

Methods

In this research, data from the China Labour Force Dynamics Survey are matched with data on PM2.5 average concentration and precipitation, and the influence of air pollution on the health expenditures of residents is analysed with econometric methods involving a two-part model, instrument variables and moderating effects.

Results

The findings reveal that air pollution significantly impacts Chinese residents’ health costs and leads to low-income people face health inequality. Specifcally, the empirical evidence shows that air pollution has no significant influence on the probability of residents’ health costs (β = 0.021, p = 0.770) but that it increases the amount of residents’ total outpatient costs (β = 0.379, p < 0.006), reimbursed outpatient cost (β = 0.453, p < 0.044) and out-of-pocket outpatient cost (β = 0.362, p < 0.048). The heterogeneity analysis of income indicates that low-income people face inequality due to health cost inflation caused by air pollution, their total and out-of-pocket outpatient cost significantly increase with PM2.5 (β = 0.417, p = 0.013; β = 0.491, p = 0.020). Further analysis reveals that social basic medical insurance does not have a remarkable positive moderating effect on the influence of air pollution on individual health inflation (β = 0.021, p = 0.292), but supplementary medical insurance for employees could reduce the effect of air pollution on low-income residents’ reimbursed and out-of-pocket outpatient cost (β=-1.331, p = 0.096; β=-2.211, p = 0.014).

Conclusion

The study concludes that air pollution increases the amount of Chinese residents’ outpatient cost and has no significant effect on the incidence of outpatient cost. However, air pollution has more significant impact on the low-income residents than the high-income residents, which indicates that air pollution leads to the inequity of medical cost. Additionally, the supplementary medical insurance reduces the inequity of medical cost caused by air pollution for the low-income employees.
Tools and frameworks for evaluating the implementation of learning health systems: a scoping review
Authors: Rajit Darren , Reeder Sandra , Johnson Alison , Enticott Joanne , Teede Helena
Published: August 2024

Introduction

Despite increased interest in learning health systems (LHS), a paucity of guidance and tools for evaluating LHS implementation exists. To address this, we aim to undertake a scoping review on existing tools and evaluation of exemplars of LHS implementation.

Methods

We conducted a scoping review of peer-reviewed studies within Scopus, EMBASE, MEDLINE, and MEDLINE in-process that described (1) the evaluation of the implementation of an operating LHS or (2) the development of a framework or tool to facilitate this evaluation. Anima, basic research, abstracts, non-English language articles, and publications before 2018 were excluded. All study designs were considered.

Findings

From 1300 studies initially identified, 4 were eligible, revealing three tools with nine implementation evaluation examples. The identified tools shared constructs which were evaluated, including: Stakeholders, Data, Research Evidence, Implementation, and Sociotechnical Infrastructure. However, there was divergence in evaluation methodology. Tools ranged from a five-point numerical rating system for process maturity with a radar chart called the Network Maturity Grid (NMG); the Kaiser Permanente Washington (KPWA) LHS Logic Model, which provides a broad list of constructs and sample measures relevant to LHS operations; and finally LADDERS, a simple tool or form-based template designed for consistent evaluation over time. The NMG tool was the most mature in terms of adaptation and adoption. Notably, two (NMG and the KPWA LHS Logic Model) out of three tools conceptualized the LHS as a suite of processes and devised tools were processes that linked these constructs.

Implications for toolkit development

The evaluation of LHS implementation remains an under explored area of investigation, as this scoping review found only three tools for LHS implementation evaluation. Our findings indicate a need for further empirical research in this area and suggest early consensus in constructs that need to be considered during evaluation.
The efficiency of clinical laboratories: the case of Kerman province
Authors: Shaker Zohreh , Shaker Zainab , Barouni Mohsen , Sabermahani Asma
Published: August 2024

Background

Medical diagnostic laboratories are an essential work environment that plays an important role in diagnosing, treating, and being sensitive to diseases. One way to evaluate laboratories’ performance is to calculate their efficiency. This study investigates the efficiency of laboratories that are related to health centers in the south of Iran.

Methods

This study was conducted in 2021. The input numbers include: the number of technical personnel and the number of cell counters, and the output data includes: the scores obtained from the level 2 health laboratory evaluation list. And efficiency was calculated with DEAP software. The analysis is accomplished by the assumption of input-oriented.

Findings

The efficiency of laboratories of Orzueeyeh and Ravar Cities had the highest efficiency with the assumption of variable returns to scale efficiency 1, and the model of all laboratories is the laboratory of Ravar City. The laboratories of Kuhbanan and Rabor cities had the lowest efficiency with the assumption of variable returns to scale efficiency of 0.859 and 0.899, respectively. The average scale efficiency, Variable returns to scale, and constant returns to scale for laboratories in the cities of Kerman province are 0.842, 0.943, and 0.895, respectively.

Conclusions

To increase the efficiency of laboratories, significant resources and funds should be used, as well as few studies have been done on the efficiency of laboratories, which requires more attention.
Vasorin (VASN) overexpression promotes pulmonary metastasis and resistance to adjuvant chemotherapy in patients with locally advanced rectal cancer
Authors: Kang Da , Huang Shanshan , Liao Yijun , Mi Siyuan , Zhou Jingying , Feng Yu , Huang Riming , Lu Zhen-hai , Pan Z. Z. , Ma Wenjuan , Chen Gong , Yue Jia-Xing , Huang Jingxiu , Zhang R. X.
Published: August 2024

Background

LARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection.

Methods

Sequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome.

Results

Our study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer.

Conclusions

Our study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance.
Improving the sexual health of women with disabilities in sub-Saharan Africa: a scoping review of published studies
Authors: Bolarinwa Obasanjo Afolabi , Odimegwu Clifford , Tapera Talent
Published: August 2024

Background

An essential aspect of human well-being is positive sexual health outcomes. However, the issue of adverse sexual health outcomes continues to be a major public health concern, particularly for women with disabilities in sub-Saharan Africa (SSA). Therefore, this current scoping review mapped studies conducted in the last twenty-nine years on the sexual health of women with disabilities from these five dimensions: sexual activity, contraceptive use, sexual autonomy, sexual violence and risky sexual behaviour, whilst seeking to identify the current state of knowledge and address the study gaps in SSA.

Methods

This current scoping review was informed by the methodological framework proposed by Arksey and O’Malley. Exploratory searches were conducted in PubMed, Web of Science, African Journals Online, etc., to identify studies conducted in SSA that focus on sexual activity, contraceptive use, sexual autonomy, sexual violence and risky sexual behaviour among women with disabilities in SSA since the inception of the International Conference on Population and Development in 1994 to 30th of March 2024. This process resulted in the inclusion of seventeen (17) studies.

Results

Of the 1362 identified through various databases, 34 studies were included for the full-text retrieval and screening; only 17 studies met the inclusion criteria. The eligible studies were conducted across six countries in SSA and published between 2008 and 2023. Eight studies used quantitative study type, six utilised qualitative approach, and three employed mixed-methods analysis. Two studies were conducted on sexual activity, ten were conducted on contraceptive use, four were conducted on sexual violence, and one study was conducted on risky sexual behaviour, whilst no study on sexual autonomy met the inclusion criteria.

Conclusion

This review showed that there were few or scarce studies on sexual activity, contraceptive use, sexual autonomy, sexual violence and risky sexual behaviour among women with disabilities in SSA and even where the studies were substantial (contraceptive use), the majority of the studies were conducted in a country. Future studies should consider examining dimensions of sexual health, such as sexual autonomy, sexual activity and risky sexual behaviour of women with disabilities that were not available or were scarce in the literature.
DF-1-Derived exosomes mediate transmission of reticuloendotheliosis virus and resist REV-specific antibodies
Authors: Wang Zhen , Cui Huizhen , Zhang Yawen , Sun Wanli , Yang Wenjie , Zhao Peng
Published: August 2024

Background

Reticuloendotheliosis virus (REV), a member of the family Retroviridae, is a hot area of research, and a previous study showed that exosomes purified from REV-positive semen were not blocked by REV-specific neutralizing antibodies and established productive infections.

Methods

To further verify the infectivity of exosomes from REV-infected cells, we isolated and purified exosomes from REV-infected DF-1 cells and identified them using Western blot and a transmission electron microscope. We then inoculated 7-day-old embryonated eggs, 1-day-old chicks and 23-week-old hens with and without antibody treatment. REV was administered simultaneously as a control.

Results

In the absence of antibodies, the results indicated that REV-exosomes and REV could infect chicks, resulting in viremia and viral shedding, compared with the infection caused by REV, REV-exosomes reduced the hatching rate and increased mortality after hatching, causing severe growth inhibition and immune organ damage in 1-day-old chicks; both REV and REV-exosomes also could infect hens, however, lead to transient infection. In the presence of antibodies, REV-exosomes were not blocked by REV-specific neutralizing antibodies and infected 7-day-old embryonated eggs. However, REV could not infect 1-day-old chicks and 23-week-old hens.

Conclusion

In this study, we compared the infectious ability of REV-exosomes and REV, REV-exosomes could escape from REV-specific neutralizing antibodies in embryonated eggs, providing new insights into the immune escape mechanism of REV.
The analgesic effects of Yu-Xue-Bi tablet (YXB) on mice with inflammatory pain by regulating LXA4-FPR2-TRPA1 pathway
Authors: Liu Ying , Zhang Guoxin , Zhu Chunyan , Yao Xuemin , Wang Wenli , Shen Li , Wang Haiping , Lin Na
Published: August 2024

Background

Oxylipins including lipoxin A4 (LXA4) facilitate the resolution of inflammation and possess analgesic properties by inhibiting macrophage infiltration and transient receptor potential (TRP) protein expression. Yu-Xue-Bi Tablet (YXB) is a traditional Chinese patent medicine used to relieve inflammatory pain. Our previous research has shown that the analgesic effect of YXB is related to inhibiting peripheral inflammation and regulating macrophage infiltration, but the mechanism is not yet clear. The purpose of this study is to explore the mechanisms of YXB on mice models with Complete Freund’s Adjuvant (CFA)-induced inflammatory pain from the perspective at the resolution of inflammation.

Methods

Mechanical allodynia thresholds and heat hypersensitivity were measured using the Von Frey test and the hot plate test respectively. The open field test and the tail suspension test were employed to measure anxiety and depressive behaviors respectively. The expression of CD68+ and the proportion of F4/80+CD11b+ cells were measured by immunofluorescence staining and flow cytometry. The expression of transient receptor potential ankyrin 1(TRPA1) was measured by immunofluorescence staining and western blotting. Oxylipins omics analysis provided quantitative data on oxylipins in the paws, and enzyme linked immunosorbent assay (ELISA) was used to measure the levels of LXA4 there. Immunofluorescence staining was used to perform the expression of Leukotriene A4 hydroxylase (LTA4H) in the paws of mice. The impact of injecting the formyl peptide receptor 2(FPR2) antagonist WRW4 and the TRPA1 agonist AITC into the left paws was observed, focusing on the expression of mechanical allodynia thresholds, the expression of CD68+, TRPA1 in the paws, and Calcitonin gene-related peptide (CGRP) in the L5 spinal dorsal horn.

Results

YXB elevated mechanical allodynia thresholds, alleviated heat hypersensitivity and anxiety and depressive behaviors in CFA mice. It significantly reduced the number of CD68+ and proportion of F4/80+CD11b+ within the paws, thereby decreasing macrophage infiltration. Additionally, it diminished the expression of TRPA1 in the paws and TRPV1 in the DRG, leading to an inhibition of peripheral sensitization. Through quantitative analysis, it was found that YXB could modulate DHA-derived oxylipins and LXA4. ELISA results indicated that YXB elevated the levels of LXA4 and inhibited the expression of LAT4H in the paws. Furthermore, the pro-resolution and analgesic effects of YXB were hindered after administration of the FPR2 antagonist. Compared with the AITC group, YXB showed no significant improvement in anti-inflammatory and analgesic effects.

Conclusions

YXB can regulate the oxylipins of paws in CFA mice to promote the resolution of inflammation. The LXA4-FPR2-TRPA1 pathway is a key mechanism for the resolution of inflammation and analgesic effects.
Astrocytic activation increases blood flow in the adult olfactory bulb
Authors: Ogino Takashi , Agetsuma Masakazu , Sawada Masato , Inada Hiroyuki , Nabekura Junichi , Sawamoto Kazunobu
Published: August 2024

Activation of astrocytes after sensory stimulation has been reported to be involved in increased blood flow in the central nervous system. In the present study, using a chemogenetic method to induce astrocyte activation in mice without sensory stimulation, we found that astrocytic activation led to increased blood flow in the olfactory bulb, suggesting that astrocyte activation is sufficient for increasing blood flow in the olfactory bulb. The technique established here will be useful for studying the mechanisms underlying sensory input-dependent blood flow increases.
Mother trees of common ash (Fraxinus excelsior) disperse different sets of mycobiome through their seed wings
Authors: Long Feng , Doonan James M. , Nielsen Lene R. , Kjær Erik D. , Kosawang Chatchai
Published: August 2024

Objective

The endophytic mycobiome is present in all studied plant compartments, including fruits and seeds. Here, we studied the mycobiome of seed wings as they are transferred with seeds in common ash and tested whether the mycobiome differs among trees. To achieve this, we used ITS1-based amplicon sequencing and two genotypes of F. excelsior as a model to compare the mycobiome of mother trees and their wings.

Results

We compared the mycobiome of 57 seed wings to the seed stalks (57) collected from two genotypes of F. excelsior using three ramets of each genotype. Alpha diversity indices (ACE, Fisher and Observed OTUs) suggested a higher richness of the mycobiome associated with the seed wing than the seed stalk within each genotype. However, there were neither significant differences in Shannon diversity between the mycobiomes from the two tissue types nor the two genotypes. PERMANOVA revealed significant differences in the mycobiome composition between tissue types (P < 0.001). It also showed a significant difference between seed wings (P = 0.04), but not between seed stalks of the two genotypes. Our results suggest that Fraxinus excelsior mother trees disperse different sets of mycobiomes with their seed wings, which may be important for germination and seedling establishment—especially in the light of ash dieback.
Can the diameter of nerve fibers be effectively utilized to enhance the accuracy of determining the length of the aganglionic segment compared to intraoperative biopsy in patients with Hirschsprung’s disease?
Authors: Talebi Ali , Kahdouei Mohammadsadegh Talebi , Memar Elmira Hajiesmaeil , Ashjaei Bahar , Raji Hojatollah , Adel Maryam Ghavami
Published: August 2024

Objective

The aim of this study is to investigate the accuracy of utilizing neural fiber trunk diameter in accurately diagnosing the length of the aganglionic segment in patients definitively diagnosed with Hirschsprung’s disease.

Results

In this study, 40 patients (19 males, 21 females; mean age 2.5 ± 2.2646 years) were assessed for Hirschsprung’s disease. Constipation was the main symptom (75%), followed by abdominal issues. All underwent contrast enema and rectal suction biopsy for diagnosis, followed by surgery (predominantly Soave and Swensen techniques). Majority (85%) had rectosigmoid involvement. Neural fiber diameter was measured, with 52.5% ≤40 μm and 47.5% >40 μm. Statistical analysis showed 40% sensitivity(CI:95%) and 47% specificity(CI:95%) with a cutoff of 40.5 μm. Cohen’s kappa index for aganglionic segment size was 0.7.
Polypoid heterotopic gastric mucosa: in terminal ileum causing extensive lower gastrointestinal bleeding without Meckel’s diverticulum: a case report
Authors: Aslanabadi Saeid , Badebarin Davoud , Ghavifekr Nazila Hasanzadeh , Ghasemi Babollah , Shoaran Maryam , Hesari Marjan
Published: August 2024

Background

Heterotopic gastric mucosa (HGM) can be located in various parts of the gastrointestinal tract. As a rare anomaly in the small intestine, it can become complicated by intussusception, obstruction, gastrointestinal bleeding, and even peritonitis, leading to death.

Case presentation

This case report focuses on a 12-year-old Middle Eastern boy who presented with hematochezia and abdominal pain for a couple of days. A tagged Red blood cell (RBC) scan and Technetium scan revealed gastrointestinal bleeding at the lower abdomen, highly suggestive of the diagnosis of Meckel’s diverticulum. Subsequently, exploratory laparotomy revealed contiguous and scattered mucosal lesions with multiple polyps of various sizes in the terminal ileum. Meckel’s diverticulum was absent, and the patient was treated with resection and primary anastomosis. The resected tissue revealed extensive ectopic gastric mucosa and polypoid tissues. The patient recovered uneventfully and was discharged four days after the surgery. The symptoms did not recur within six months after his surgery.

Conclusion

Our case demonstrated that despite the rarity of multiple polypoid gastric heterotopias in the terminal ileum, it should be considered as one of the differential diagnoses of gastrointestinal tract bleeding.
Exploring the genetic variability of the PRNP gene at codons 127, 142, 146, 154, 211, 222, and 240 in goats farmed in the Lombardy Region, Italy
Authors: Ferrari Carlotta , Punturiero Chiara , Milanesi Raffaella , Delledonne Andrea , Bagnato Alessandro , Strillacci Maria G.
Published: August 2024

Scrapie is a transmissible spongiform encephalopathy affecting sheep and goats. The prion protein-encoding gene (PRNP) plays a crucial role in determining susceptibility and resistance to scrapie. At the European level, surveillance of scrapie is essential to prevent the spread of the disease to livestock. According to the Regulation EU 2020/772 polymorphisms K222, D/S146 could function as resistance alleles in the genetic management of disease prevention. In Italy, a breeding plan for scrapie eradication has not been implemented for goats. However, surveillance plans based on the PRNP genotype have been developed as a preventive measure for scrapie. This research aimed to describe the polymorphisms at 7 positions within the PRNP gene in 956 goats of the Alpine, Saanen and mixed populations farmed in the Lombardy Region in Italy. PRNP polymorphisms were detected using single nucleotide polymorphism markers included in the Neogen GGP Goat 70 k chip. The K222 allele occurred in all populations, with frequencies ranging from 2.1 to 12.7%. No animals carried the S/D146 resistance allele. However, it has been demonstrated that polymorphisms in the other positions analysed could influence resistance or susceptibility to scrapie outbreaks in different ways. Ten potentially distinct haplotypes were found, and the most prevalent of the three populations was H2, which differed from the wild type (H1) in terms of mutation (S vs P) at codon 240. This study provided additional information on the genetic variability of the PRNP gene in these populations in the Lombardy region of Italy, contributing to the development of genetic control measures for disease prevention.
Building the fracture network model for the Okuaizu geothermal field based on microseismic data analysis
Authors: Darisma Dian , Mukuhira Yusuke , Okamoto Kyosuke , Aoyogi Naoki , Uchide Takahiko , Ishibashi Takuya , Asanuma Hiroshi , Ito Takatoshi
Published: August 2024

Understanding flow behavior in a geothermal reservoir is important for managing sustainable geothermal energy extraction. Fluid flow in geothermal reservoirs generally occurs in complex existing fracture systems in which the reservoirs are situated in highly fractured rocks. To simulate a discrete fracture model, the location and orientation of the fracture were computed using statistical processes and observational data. In many cases, estimating the location and orientation of fractures from 1D borehole logging data is challenging. In this study, we used microseismic data to build the fracture network systems and extract the detailed positions and dimensions of the fractures. We used the microseismic data recorded at the Okuaizu Geothermal Field, Fukushima Prefecture, Japan, from 2019 to 2021. First, we located the hypocenters, removing the effect of uncertainty in the velocity structure of the geothermal fluids. We relocated and clustered the seismic events based on waveform similarity. We analyzed each cluster to define the fracture orientation using principal component analysis (PCA) and focal mechanism (FM) analysis. We used the P polarity with the S/P ratio as a constraint for a better fault-plane solution. With PCA, we can extract the fracture dimension of each cluster. Our cluster analysis showed that the clusters were not always planar fractures, and we interpreted them as fracture zones. Based on the consistency between PCA and FM, each cluster/fracture zone was classified into three conceptual models to characterize the fracture network system in this field. This model showed variations in the orientation of small fractures within the fracture zone. We characterized the spatial variation in fracture distribution and orientations in the reservoir and demonstrated the fracture network system of this field. The fracture zone near the injection well has a N–S strike, and the dip is above 80°; however, the fracture zone in the northeastern part of the injection well has a NW–SE strike with a dip between 60° and 80°. The fracture network system estimated in this study is crucial for robust reservoir modeling because our model is more realistic, observation-orientated, and includes local anomalies of reservoir properties.

Graphical Abstract
Radiomics nomogram based on CT radiomics features and clinical factors for prediction of Ki-67 expression and prognosis in clear cell renal cell carcinoma: a two-center study
Authors: Li Ben , Zhu Jie , Wang Yanmei , Xu Yuchao , Gao Zhaisong , Shi Hailei , Nie Pei , Zhang Ju , Zhuang Yuan , Wang Zhenguang , Yang Guangjie
Published: August 2024

Objectives

To develop and validate a radiomics nomogram combining radiomics features and clinical factors for preoperative evaluation of Ki-67 expression status and prognostic prediction in clear cell renal cell carcinoma (ccRCC).

Methods

Two medical centers of 185 ccRCC patients were included, and each of them formed a training group (n = 130) and a validation group (n = 55). The independent predictor of Ki-67 expression status was identified by univariate and multivariate regression, and radiomics features were extracted from the preoperative CT images. The maximum relevance minimum redundancy (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO) were used to identify the radiomics features that were most relevant for high Ki-67 expression. Subsequently, clinical model, radiomics signature (RS), and radiomics nomogram were established. The performance for prediction of Ki-67 expression status was validated using area under curve (AUC), calibration curve, Delong test, decision curve analysis (DCA). Prognostic prediction was assessed by survival curve and concordance index (C-index).

Results

Tumour size was the only independent predictor of Ki-67 expression status. Five radiomics features were finally identified to construct the RS (AUC: training group, 0.821; validation group, 0.799). The radiomics nomogram achieved a higher AUC (training group, 0.841; validation group, 0.814) and clinical net benefit. Besides, the radiomics nomogram provided a highest C-index (training group, 0.841; validation group, 0.820) in predicting prognosis for ccRCC patients.

Conclusions

The radiomics nomogram can accurately predict the Ki-67 expression status and exhibit a great capacity for prognostic prediction in patients with ccRCC and may provide value for tailoring personalized treatment strategies and facilitating comprehensive clinical monitoring for ccRCC patients.
Characteristics of patients with difficult-to-treat rheumatoid arthritis: a descriptive retrospective cohort study
Authors: Qi Wen , Robert Antoine , Singbo Narcisse , Ratelle Lucie , Fortin Paul R. , Bessette Louis , Brown Jacques P. , Michou Laëtitia
Published: August 2024

Background

In 2021, an EULAR task force published a definition of difficult-to-treat rheumatoid arthritis (D2T RA). Our current knowledge of D2T RA with the EULAR definition is based on European and Asian cohorts, and no North American cohort has yet to be published. The aim of this study was to compare D2T RA patients to non-D2T RA who are good responders to advanced therapy, and to describe their evolution in an university health center patient cohort.

Methods

This is a retrospective single centre study of the medical records of all adults with RA on at least one biologic or target synthetic DMARD (b/tsDMARD). D2T RA group was defined according to the EULAR definition of D2T RA. The non-D2T RA group was defined as a b/tsDMARD good responder who had low-disease activity or remission for at least one year on 1 or 2 b/tsDMARD mechanism of action. We compared the patients’ comorbidities, and history of b/tsDMARD use. Descriptive statistics and proportions were calculated. Kaplan-Meier analysis with log-rank test was used to estimate and compare median survival.

Results

Among the 417 patients, 101 (24%) were D2T RA and 316 (76%) were non-D2T RA. D2T RA group was slightly younger (63 ± 9 years versus 65 ± 12 years, p = 0.045), more likely to have concomitant non-inflammatory pain (28% versus 8%, p < 0.0001) and to discontinue at least one b/tsDMARD due to intolerance (39% versus 10%, p < 0.0001). In the D2T RA group, JAK inhibitors were associated with longer drug continuation when used as the third b/tsDMARD. Fewer patients were using corticosteroid at their most recent follow-up in this Canadian cohort compared to others (16% versus from 29 to 74%).

Conclusion

Concomitant non-inflammatory pain was more prevalent in D2T RA patients compared to b/tsDMARD good responder non-D2T RA patients. Steroid-sparing strategies is possible even in D2T RA patients. Future prospective research may compare JAK inhibitors with other mechanisms of action in D2T RA.
Volatilization of benzene on soil surface under different factors: evaluation and modeling
Authors: Wang Qian , Bian Jianmin , Ruan Dongmei
Published: August 2024

The volatilization of volatile organic compounds following a leakage event is a crucial mechanism that influences their migration and transformation in the soil. It is noteworthy that this process is intricately shaped by soil properties and environmental factors, exhibiting highly complex nonlinear relationships. However, there is currently no reliable mathematical model to predict the nonlinear relationship. To address this gap, the study conducted dynamic experiments considering various factors, including particle size, organic matter content, temperature, wind speed and moisture content. The volatilization rate ($$k$$
k
), an important parameter in volatilization kinetics reflecting the speed of volatilization, was calculated by first-order kinetic principle. Finally, an innovative approach was introduced using a Back Propagation Neural Network (BPNN) model for prediction. The findings indicate that wind speed exerts the most significant impact on the volatilization rate of benzene among the examined factors. The application of BPNN demonstrates the model's accuracy in simulating benzene volatilization rates under diverse conditions. The results of K-fold cross-validation alleviate concerns of potential over-prediction, affirming the reliability of the constructed model. This research introduces a novel methodology for predicting volatilization parameters in real-world scenarios.