bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunomodulatory effects of epiphytic Loranthus micranthus leaf extracts collected from two host plants: Psidium guajava and Parkia biglobosa
Authors: Idoko Ngozi Dorathy , Chukwuma Ifeoma Felicia , Nworah Florence Nkechi , Mba Sopuruchukwu Elizabeth , Joshua Parker Elijah , Nwodo Okwesilieze Fred Chiletugo , Abusudah Wafaa Fouzi , Almohmadi Najlaa Hamed , de Waard Michel
Published: January 2024

Background

Immunological abnormalities are implicated in the pathogenesis of many chronic diseases. Due to the drug-related adverse effects of currently available orthodox immunomodulators, natural immunomodulators are being looked upon as potential agents to replace them in therapeutic regimens. This research aimed to investigate the immunomodulatory potential ofL. micranthusextracts epiphytic onPsidium guajava(LMPGE) andParkia biglobosa(LMPBE).

Methods

Phytochemical screening and acute toxicity testing were carried out to identify the phytoconstituents and safety profiles of the extracts. The extracts’ innate and adaptive immunomodulatory potentials were determined in experimental animals using in vivo leucocyte mobilization, delayed-type hypersensitivity (DTH) response, hemagglutination antibody titre, and cyclophosphamide-induced myelosuppression models. Levamisole was used as the standard drug throughout the study.

Results

Compared to LMPBE, LMPGE contained significantly (p <  0.05) more tannins, cyanogenic glycosides, saponins, reducing sugars, glycosides, flavonoids, and alkaloids. Furthermore, the groups treated with the extracts had a significant (p <  0.05) increase in the total number of leucocytes, neutrophils, basophils, and antibody titers relative to the untreated control. In the same way, the treatment raised TLC in cyclophosphamide-intoxicated rats, with 250 mg/kg b. w. of LMPGE and LMPBE recording 9712.50 ± 178.00 and 8000.00 ± 105.00 ×  109 /L, respectively, compared to 3425.00 ± 2 5.00 × 109 /L in the untreated group. Overall, LMPGE was more effective.

Conclusions

The findings from this study suggest thatL. micranthusepiphytic inPsidium guajavaandParkia biglobosahas possible immune stimulating potential.
Shikonin reactivates TSGs GADD45B and PPP3CC to block NSCLC cell proliferation and migration through JNK/P38/MAPK signaling pathways
Authors: Zhao Yujia , Wu Dan , Fu Zhenkai , Liu Wenna , Yao Yu , Liang Ying
Published: January 2024

Background

Shikonin, a natural naphthoquinone compound extracted from the Chinese traditional herbal medicine “Lithospermum erythrorhizon”, possesses antitumor activity against various cancer types. Tumor-suppressor genes (TSGs) negatively regulate cell growth, proliferation, and differentiation, thereby inhibiting tumor formation. However, the molecular mechanism of action of shikonin on TSGs in non–small-cell lung cancer (NSCLC) remains unclear.

Methods

The inhibitory effect of shikonin on the proliferation and migration abilities of lung cancer cells were measured by Cell Counting Kit 8 (CCK8) and wound healing assays. The alteration of genes by shikonin treatment was detected by mRNA high-throughput sequencing and further confirmed by qPCR and western blotting experiments. The dominant functions of the upregulated genes were analyzed by GO and KEGG profiling.

Results

Shikonin inhibited the proliferation and migration of A549 and H1299 NSCLC cells in a dose-dependent manner. mRNA high-throughput sequencing revealed a total of 1794 upregulated genes in shikonin-treated NSCLC cells. Moreover, bioinformatic analysis of GO and KEGG profiling revealed that the up-regulated genes were mostly involved in the JNK/P38/MAPK signaling pathway, among which the expression of GADD45B and PPP3CC was significantly enhanced. Finally, we confirmed that GADD45B and PPP3CC were indeed upregulated in JNK/P38/MAPK pathway.

Conclusions

Taken together, these results suggested that shikonin might affect the expression of GADD45B and PPP3CC through the JNK/P38/MAPK pathway, therefore exerting an inhibitory effect on the proliferation and migration of cancer cells. To our knowledge, this is the first study reporting the role of shikonin in upregulating TSGs to activate the JNK/P38/MAPK signaling pathways in NSCLC.
Prevalence and varieties of complementary and alternative medicine usage among individuals with pre-dialysis chronic kidney disease in Taiwan: an investigative cross-sectional analysis
Authors: Tsai Ming-Yen , Huang Yu-Chuen , Cheng Ben-Chung , Chin Chieh-Ying , Hsu Yung-Tang , Lee Wen-Chin
Published: January 2024

Background

Complementary and alternative medicine (CAM) is frequently used in the general population, yet only limited data are available regarding the prevalence of these medications in patients with chronic kidney disease (CKD). Hence, our study aimed to explore the prevalence and types of CAM in Taiwanese patients with CKD.

Methods

A cross-sectional questionnaire survey was conducted by face-to-face interview of 275 pre-dialysis patients without dialysis treatment or kidney transplant at an outpatient nephrology clinic in Taiwan from March 2021 to June 2023. The study outcomes were the prevalence of CAM, CAM types, reasons for using CAM, and sources of information about CAM.

Results

Overall, 128 patients (46.5%) were using CAM, but no significant differences from non-CAM users in the various CKD stages (p = 0.156) were found. CAM usage was high in the age range of 20–60 years and duration of CKD ≤ 5 years (p < 0.05). The most commonly used type of CAM was nutritional approaches (79.7%), followed by other complementary health approaches (26.6%). The most commonly utilized modalities of CAM were vitamins and minerals (38.3%), and only 27.1% of patients disclosed their CAM use to their physicians. The most common sources of information about CAM were family and friends, cited by 66% of the participants. Health promotion and a proactive attitude were reported by 40% of users as the reasons for using CAM.

Conclusions

The present study provides data on the CAM usage among CKD patients and adds to the increasing evidence on CAM use. Because some of these practices have safety concerns, better education from healthcare providers on the risks and benefits of CAM therapy is needed by CKD patients.
Flaxseed oil fraction reverses cardiac remodeling at a molecular level: improves cardiac function, decreases apoptosis, and suppresses miRNA-29b and miRNA 1 gene expression
Authors: Boshra Sylvia A. , Nazeam Jilan A. , Esmat Ahmed
Published: January 2024

Flaxseed is an ancient commercial oil that historically has been used as a functional food to lower cholesterol levels. However, despite its longstanding treatment, there is currently a lack of scientific evidence to support its role in the management of cardiac remodeling. This study aimed to address this gap in knowledge by examining the molecular mechanism of standardized flaxseed oil in restoring cardiac remodeling in the heart toxicity vivo model. The oil fraction was purified, and the major components were standardized by qualitative and quantitative analysis. In vivo experimental design was conducted using isoproterenol ISO (85 mg/kg) twice subcutaneously within 24 h between each dose. The rats were treated with flaxseed oil fraction (100 mg/kg orally) and the same dose was used for omega 3 supplement as a positive control group. The GC-MS analysis revealed that α-linolenic acid (24.6%), oleic acid (10.5%), glycerol oleate (9.0%) and 2,3-dihydroxypropyl elaidate (7%) are the major components of oil fraction. Physicochemical analysis indicated that the acidity percentage, saponification, peroxide, and iodine values were 0.43, 188.57, 1.22, and 122.34 respectively. As compared with healthy control, ISO group-induced changes in functional cardiac parameters. After 28-day pretreatment with flaxseed oil, the results indicated an improvement in cardiac function, a decrease in apoptosis, and simultaneous prevention of myocardial fibrosis. The plasma levels of BNP, NT-pro-BNP, endothelin-1, Lp-PLA2, and MMP2, and cTnI and cTn were significantly diminished, while a higher plasma level of Topo 2B was observed. Additionally, miRNA − 1 and 29b were significantly downregulated. These findings provide novel insight into the mechanism of flaxseed oil in restoring cardiac remodeling and support its future application as a cardioprotective against heart diseases.
Machine learning algorithms for the prediction of adverse prognosis in patients undergoing peritoneal dialysis
Authors: Yang Jie , Wan Jingfang , Feng Lei , Hou Shihui , Yv Kaizhen , Xu Liang , Chen Kehong
Published: January 2024

Background

An appropriate prediction model for adverse prognosis before peritoneal dialysis (PD) is lacking. Thus, we retrospectively analysed patients who underwent PD to construct a predictive model for adverse prognoses using machine learning (ML).

Methods

A retrospective analysis was conducted on 873 patients who underwent PD from August 2007 to December 2020. A total of 824 patients who met the inclusion criteria were included in the analysis. Five commonly used ML algorithms were used for the initial model training. By using the area under the curve (AUC) and accuracy (ACC), we ranked the indicators with the highest impact and displayed them using the values of Shapley additive explanation (SHAP) version 0.41.0. The top 20 indicators were selected to build a compact model that is conducive to clinical application. All model-building steps were implemented in Python 3.8.3.

Results

At the end of follow-up, 353 patients withdrew from PD (converted to haemodialysis or died), and 471 patients continued receiving PD. In the complete model, the categorical boosting classifier (CatBoost) model exhibited the strongest performance (AUC = 0.80, 95% confidence interval [CI] = 0.76–0.83; ACC: 0.78, 95% CI = 0.72–0.83) and was selected for subsequent analysis. We reconstructed a compression model by extracting 20 key features ranked by the SHAP values, and the CatBoost model still showed the strongest performance (AUC = 0.79, ACC = 0.74).

Conclusions

The CatBoost model, which was built using the intelligent analysis technology of ML, demonstrated the best predictive performance. Therefore, our developed prediction model has potential value in patient screening before PD and hierarchical management after PD.
Influence of perceived parental child-rearing attitudes and ego identity on college adjustment among Korean nursing students
Authors: Choi Hye Seon , Lee Sona , Seo Eunju
Published: January 2024

Background

This study aimed to examine the relationship between nursing students’ perceived parental child-rearing attitude, ego identity, and college adjustment in Korea and explore factors that influence college adjustment.

Methods

This study surveyed 224 nursing students enrolled in universities located in two regions within South Korea. Data were collected from October 14 to November 31, 2019. Perceived parental child-rearing attitude (paternal emotional warmth, paternal rejection, paternal overprotection, maternal emotional warmth, maternal rejection, and maternal overprotection) and ego identity of nursing students were used as independent variables on college adjustment. Collected data were subjected to correlation analysis using SPSS version 26.0 for Windows. Further, regression analysis was performed on the influence of parental child-rearing attitude and ego identity on college adjustment.

Results

Among the parental child-rearing attitudes, paternal emotional warmth (r = .30, p < .001), maternal emotional warmth (r = .38, p < .001), and ego identity (r = .71, p < .001) were positively correlated with nursing students’ college adjustment, whereas maternal rejection was negatively correlated with ego identity (r = − .28, p < .001) and college adjustment (r = − .15, p = .025). Regression analysis of the effects of nursing students’ perceived parental child-rearing attitude and ego identity on college adjustment, with grade as a control variable, revealed that ego identity (p < .001) had a significant effect on college adjustment, and the higher the ego identity (β = 0.712), the higher the college adjustment. Further, the explanatory power of explaining college adjustment was high at 49.9%.

Conclusions

The nursing students’ perceived paternal emotional warmth, maternal emotional warmth, and ego identity were positively correlated with college adjustment. Additionally, ego identity was found as the influencing factor in Korean nursing students’ college adjustment. Therefore, programs to strengthen ego identity should be developed and implemented for college adjustment among nursing students.
Supporting self-management in women with pre-existing diabetes in pregnancy: a mixed-methods sequential comparative case study
Authors: Sushko Katelyn , Strachan Patricia , Butt Michelle , Nerenberg Kara , Sherifali Diana
Published: January 2024

Introduction

Maternal glycemia is associated with pregnancy outcomes. Thus, supporting the self-management experiences and preferences of pregnant women with type 1 and type 2 diabetes is crucial to optimize glucose control and perinatal outcomes.

Research design and methods

This paper describes the mixed methods integration of a sequential comparative case study. The objectives are threefold, as we integrated the quantitative and qualitative data within the overall mixed methods design: (1) to determine the predictors of glycemic control during pregnancy; (2) to understand the experience and diabetes self-management support needs during pregnancy among women with pre-existing diabetes; (3) to assess how self-management and support experiences helpe to explain glycemic control among women with pre-existing diabetes in pregnancy. The purpose of the mixing was to integrate the quantitative and qualitative data to develop rich descriptive cases of how diabetes self-management and support experiences and preferences in women with type 1 and type 2 diabetes during pregnancy help explain glucose control. A narrative approach was used to weave together the statistics and themes and the quantitative results were integrated visually alongside the qualitative themes to display the data integration.

Results

The quantitative results found that women achieved “at target” glucose control (mean A1C of the cohort by the third visit: 6.36% [95% Confidence Interval 6.11%, 6.60%]). The qualitative findings revealed that feelings of fear resulted in an isolating and mentally exhausting pregnancy. The quantitative data also indicated that women reported high levels of self-efficacy that increased throughout pregnancy. Qualitative data revealed that women who had worked hard to optimize glycemia during pregnancy were confident in their self-management. However, they lacked support from their healthcare team, particularly around self-management of diabetes during labour and delivery.

Conclusions

The achievement of optimal glycemia during pregnancy was motivated by fear of pregnancy complications and came at a cost to women’s mental health. Mental health support, allowing women autonomy, and the provision of peer support may improve the experience of diabetes self-management during pregnancy. Future work should focus on developing, evaluating and implementing interventions that support these preferences.
Investigating safe nursing care and medication safety competence in nursing students: a multicenter cross-sectional study in Iran
Authors: Mohebi Zahra , Bijani Mostafa , Dehghan Azizallah
Published: January 2024

Background

Medication safety competence is very important as one of the clinical skills among nursing students to provide safe nursing care. The lack of medication safety competence in nursing students leads to occurrence of medication errors subsequently jeopardizing patient safety. Thus, the present study was conducted to investigate safe nursing care and medication safety competence among nursing students in the south of Iran.

Methods

A descriptive cross-sectional multicenter study was conducted from September to December 2022. The research population included nursing students of three universities of medical sciences in Fars Province, Southern Iran. A total of 310 nursing students who were selected through convenience sampling participated in the study. The data collection instruments consisted of a demographics survey, Medication Safety Competence Scale (MSCS), and a Safe Nursing Care Scale (SNCS). The collected data were analyzed using descriptive statistics (absolute and relative frequency, mean and standard deviation) and inferential statistics (Independent t-test, Analysis of variance and Pearson correlation coefficient). The data were analyzed in SPSS 23 and the level of significance was considered 0.05.

Results

The mean age of the participants was 22.53 ± 1.69 years. The total mean scores for medication safety competence and safe nursing care were found to be 111.97 ± 11.85 and 105.12 ± 11.64, respectively. There was a statistically significant positive correlation between safe nursing care and medication safety competence (r = 0.084, P < 0.001).

Conclusion

The mean scores of nursing students’ medication safety competence and safe nursing care were at an average level. To maintain patient safety, nursing instructors and managers are recommended to employ appropriate strategies to improve medication safety competence and safe nursing care in nursing students.
CC chemokine receptors are prognostic indicators of gastric cancer and are associated with immune infiltration
Authors: Liao Xinghe , Yang Yong , Wang Lihuan , Kong Zhiyuan , Li Weiping
Published: January 2024

Background

CC chemokine receptors are responsible for regulating the tumor microenvironment (TME) and participating in carcinogenesis and tumor advancement. However, no functional study has investigated CC chemokine receptors in gastric cancer (GC) prognosis, risk, immunotherapy, or other treatments.

Methods

We conducted a bioinformatics analysis on GC data using online databases, including the Human Protein Atlas (HPA), Kaplan-Meier (KM) plotter, GeneMANIA, MethSurv, the University of ALabama at Birmingham CANcer (UALCAN) Data Analysis Portal, Gene Set Cancer Analysis (GSCA), cBioportal, and Tumor IMmune Estimation Resource (TIMER).

Results

We noted that CC chemokine receptor expression correlated with survival in GC. CC chemokine receptor expression was also strongly linked to different tumor-infiltrating immune cells. Additionally, CC chemokine receptors were found to be broadly drug-resistant in GC.

Conclusion

Our study identifed CC chemokine receptor expression helped in predicting the prognosis of patients diagnosed with GC. The expression level of the CC chemokine receptors was also positively related to multiple tumor-infiltrating lymphocytes (TILs). These findings provide evidence to monitor patients with GC using CC chemokine receptors, which can be used as an effective biomarker for predicting the disease prognosis and be regarded as a therapeutic target for modulating the tumor immune microenvironment.
Identification of a novel lymphangiogenesis signature associated with immune cell infiltration in colorectal cancer based on bioinformatics analysis
Authors: Liu Hong , Shi Huiwen , Sun Yinggang
Published: January 2024

Background

Lymphangiogenesis plays an important role in tumor progression and is significantly associated with tumor immune infiltration. However, the role and mechanisms of lymphangiogenesis in colorectal cancer (CRC) are still unknown. Thus, the objective is to identify the lymphangiogenesis-related genes associated with immune infiltration and investigation of their prognosis value.

Methods

mRNA expression profiles and corresponding clinical information of CRC samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The lymphangiogenesis-related genes (LymRGs) were collected from the Molecular Signatures database (MSigDB). Lymphangiogenesis score (LymScore) and immune cell infiltrating levels were quantified using ssGSEA. LymScore) and immune cell infiltrating levels-related hub genes were identified using weighted gene co-expression network analysis (WGCNA). Univariate Cox and LASSO regression analyses were performed to identify the prognostic gene signature and construct a risk model. Furthermore, a predictive nomogram was constructed based on the independent risk factor generated from a multivariate Cox model.

Results

A total of 1076 LymScore and immune cell infiltrating levels-related hub genes from three key modules were identified by WGCNA. Lymscore is positively associated with natural killer cells as well as regulator T cells infiltrating. These modular genes were enriched in extracellular matrix and structure, collagen fibril organization, cell-substrate adhesion, etc. NUMBL, TSPAN11, PHF21A, PDGFRA, ZNF385A, and RIMKLB were eventually identified as the prognostic gene signature in CRC. And patients were divided into high-risk and low-risk groups based on the median risk score, the patients in the high-risk group indicated poor survival and were predisposed to metastasis and advanced stages. NUMBL and PHF21A were upregulated but PDGFRA was downregulated in tumor samples compared with normal samples in the Human Protein Atlas (HPA) database.

Conclusion

Our finding highlights the critical role of lymphangiogenesis in CRC progression and metastasis and provides a novel gene signature for CRC and novel therapeutic strategies for anti-lymphangiogenic therapies in CRC.
Association of MBL2 gene polymorphisms and MBL levels with dilated cardiomyopathy in a Chinese Han population
Authors: Mao Yujie , Wei Hong , Gong Yugang , Peng Lei , Chen Yu
Published: January 2024

Background

It has been reported that Mannose-binding lectin 2 (MBL2) gene polymorphisms and expression levels are related to dilated cardiomyopathy (DCM). This study aimed to investigate the potential association between MBL2 gene polymorphisms and the pathogenesis of DCM.

Methods

Five single nucleotide polymorphisms (SNPs) of the MBL2 gene were genotyped in 440 DCM patients and 532 controls in Southwest China. A luciferase reporter assay was used to detect the transcriptional activity the different genotypes. MBL serum levels, left ventricle ejection fraction (LVEF) and lower left ventricular end-diastolic diameter (LVEDD) were measured.

Results

The rs11003125 C allele increased the transcriptional activity of the MBL2 promoter compared with the rs11003125 G allele. The rs11003125 CC carriers had higher MBL serum levels, LVEF and LVEDD than the rs11003125 CG and GG carriers.

Conclusions

Our study first revealed that MBL2 polymorphisms and serum MBL levels were associated with DCM. Allele C in rs11003125 of MBL2 may upregulate the expression levels of MBL. High serum MBL levels may be a protective factor in DCM pathogenesis.
RNA m6A methylation regulators in liver cancer
Authors: Xu Qiaoping , Ren Ning , Ren Lanqi , Yang Yibei , Pan Junjie , Shang Hongkai
Published: January 2024

Liver cancer is one of the most common cancers in the world and a primary cause of cancer-related death. In recent years, despite the great development of diagnostic methods and targeted therapies for liver cancer, the incidence and mortality of liver cancer are still on the rise. As a universal post-transcriptional modification, N6-methyladenosine (m6A) modification accomplishes a dynamic and reversible m6A modification process, which is executed by three types of regulators, methyltransferases (called writers), demethylases (called erasers) and m6A-binding proteins (called readers). Many studies have shown that m6A RNA methylation has an important impact on RNA metabolism, whereas its regulation exception is bound up with the occurrence of human malignant tumors. Aberrant methylation of m6A RNA and the expression of related regulatory factors may be of the essence in the pathogenesis and progression of liver cancer, yet the precise molecular mechanism remains unclear. In this paper, we review the current research situations of m6A methylation in liver cancer. Among the rest, we detail the mechanism by which methyltransferases, demethylases and m6A binding proteins regulate the occurrence and development of liver cancer by modifying mRNA. As well as the potential effect of m6A regulators in hepatocarcinogenesis and progression. New ideas and approaches will be given to the prevention and treatment of liver cancer through the following relevant research results.
Effect of test duration and sensor location on the reliability of standing balance parameters derived using body-mounted accelerometers
Authors: Abdollah Vahid , Noamani Alireza , Ralston John , Ho Chester , Rouhani Hossein
Published: January 2024

Background

Balance parameters derived from wearable sensor measurements during postural sway have been shown to be sensitive to experimental variables such as test duration, sensor number, and sensor location that influence the magnitude and frequency-related properties of measured center-of-mass (COM) and center-of-pressure (COP) excursions. In this study, we investigated the effects of test duration, the number of sensors, and sensor location on the reliability of standing balance parameters derived using body-mounted accelerometers.

Methods

Twelve volunteers without any prior history of balance disorders were enrolled in the study. They were asked to perform two 2-min quiet standing tests with two different testing conditions (eyes open and eyes closed). Five inertial measurement units (IMUs) were employed to capture postural sway data from each participant. IMUs were attached to the participants’ right legs, the second sacral vertebra, sternum, and the left mastoid processes. Balance parameters of interest were calculated for the single head, sternum, and sacrum accelerometers, as well as, a three-sensor combination (leg, sacrum, and sternum). Accelerometer data were used to estimate COP-based and COM-based balance parameters during quiet standing. To examine the effect of test duration and sensor location, each 120-s recording from different sensor locations was segmented into 20-, 30-, 40-, 50-, 60-, 70-, 80-, 90-, 100-, and 110-s intervals. For each of these time intervals, time- and frequency-domain balance parameters were calculated for all sensor locations.

Results

Most COM-based and COP-based balance parameters could be derived reliably for clinical applications (Intraclass-Correlation Coefficient, ICC ≥ 0.90) with a minimum test duration of 70 and 110 s, respectively. The exceptions were COP-based parameters obtained using a sacrum-mounted sensor, especially in the eyes-closed condition, which could not be reliably used for clinical applications even with a 120-s test duration.

Conclusions

Most standing balance parameters can be reliably measured using a single head- or sternum-mounted sensor within a 120-s test duration. For other sensor locations, the minimum test duration may be longer and may depend on the specific test conditions.
Feasibility of laparoscopic versus open pancreatoduodenectomy following neoadjuvant chemotherapy for borderline resectable pancreatic cancer: a retrospective cohort study
Authors: Li Zheng , Zhuo Qifeng , Li Borui , Liu Mengqi , Chen Chen , Shi Yihua , Xu Wenyan , Liu Wensheng , Ji Shunrong , Yu Xianjun , Xu Xiaowu
Published: January 2024

Background

There is no evidence supporting the feasibility of laparoscopic pancreaticoduodenectomy (LPD) compared to open pancreatoduodenectomy (OPD) following neoadjuvant chemotherapy (NACT) for pancreatic ductal adenocarcinoma (PDAC).

Methods

The clinical data of consecutive patients with borderline resectable PDAC who received NACT and underwent either LPD or OPD between January 2020 and December 2022 at Fudan University Shanghai Cancer Center was prospectively collected and retrospectively analyzed.

Results

The analysis included 57 patients in the OPD group and 20 in the LPD group. Following NACT, the LPD group exhibited a higher median CA19-9 decrease rate compared to the OPD group (85.3% vs. 66.9%, P = 0.042). Furthermore, 3 anatomically borderline PDACs in the LPD group and 5 in the OPD group were downstaged into resectable status (30.0% vs. 12.3%, P = 0.069). According to RECIST criteria, 51 (66.2%) patients in the entire cohort were evaluated as having stable disease. The median operation time for the LPD group was longer than the OPD group (419 vs. 325 min, P < 0.001), while the venous resection rate was 35.0% vs. 43.9%, respectively (P = 0.489). There was no difference in the number of retrieved lymph nodes, with a median number of 18.5 in the LPD group and 22 in the OPD group, and the R1 margin rate (15.0% vs. 12.3%) was also comparable. The incidence of Clavien-Dindo complications (35.0% vs. 66.7%, P = 0.018) was lower in the LPD group compared to the OPD group. Multivariable regression analysis revealed that a tumor diameter > 3 cm before NACT (HR 2.185) and poor tumor differentiation (HR 1.805) were independent risk factors for recurrence-free survival, and a decrease rate of CA19-9 > 70% (OR 0.309) was a protective factor for early tumor recurrence and overall survival.

Conclusions

LPD for PDAC following NACT is feasible and oncologically equivalent to OPD. Effective control of CA19-9 levels is beneficial in reducing early tumor recurrence and improving overall survival.
Application of an artificial intelligence-based system in the diagnosis of breast ultrasound images obtained using a smartphone
Authors: Mori Ryutaro , Okawa Mai , Tokumaru Yoshihisa , Niwa Yoshimi , Matsuhashi Nobuhisa , Futamura Manabu
Published: January 2024

Background

Breast ultrasound (US) is useful for dense breasts, and the introduction of artificial intelligence (AI)-assisted diagnoses of breast US images should be considered. However, the implementation of AI-based technologies in clinical practice is problematic because of the costs of introducing such approaches to hospital information systems (HISs) and the security risk of connecting HIS to the Internet to access AI services. To solve these problems, we developed a system that applies AI to the analysis of breast US images captured using a smartphone.

Methods

Training data were prepared using 115 images of benign lesions and 201 images of malignant lesions acquired at the Division of Breast Surgery, Gifu University Hospital. YOLOv3 (object detection models) was used to detect lesions on US images. A graphical user interface (GUI) was developed to predict an AI server. A smartphone application was also developed for capturing US images displayed on the HIS monitor with its camera and displaying the prediction results received from the AI server. The sensitivity and specificity of the prediction performed on the AI server and via the smartphone were calculated using 60 images spared from the training.

Results

The established AI showed 100% sensitivity and 75% specificity for malignant lesions and took 0.2 s per prediction with the AI sever. Prediction using a smartphone required 2 s per prediction and showed 100% sensitivity and 97.5% specificity for malignant lesions.

Conclusions

Good-quality predictions were obtained using the AI server. Moreover, the quality of the prediction via the smartphone was slightly better than that on the AI server, which can be safely and inexpensively introduced into HISs.
The association between serum testosterone level and congestive heart failure in US male adults: data from National Health and Nutrition Examination Survey (NHANES) 2011–2016
Authors: Zhan Xiangpeng , Liu Yang , Chen Tao , Wan Hao , Xiong Situ , Li Sheng , Deng Xinxi , Chen Luyao , Fu Bin
Published: January 2024

Background

This study aimed to investigate the relationship between serum testosterone levels and the risk of congestive heart failure (CHF) in adult males. Previous research has suggested a potential link between serum testosterone and cardiovascular health, but the findings have been inconclusive.

Methods

This study was cross-sectional, and the data were obtained from the 2011–2016 cycle of the National Health and Nutrition Examination Survey (NHANES), which included a sample of 6,841 male participants. Serum testosterone levels were measured using a standardized assay, and CHF status was assessed through self-reporting. Covariates such as age, ethnicity, lifestyle factors, and health conditions were considered in the analysis.

Results

Among the participants, 242 individuals had a documented history of CHF. We observed a linear correlation between serum testosterone levels and CHF occurrence, with higher serum testosterone levels associated with a decreased risk of CHF (Q4 vs. Q1, OR = 0.29, 95% CI: 0.19–0.47, P < 0.001). After adjusting for confounding variables, multivariate analysis revealed that high serum testosterone levels remained significantly associated with a lower risk of CHF (OR: 0.47, 95% CI: 0.27–0.80, P = 0.01). Subgroup analysis indicated a significant association between high serum testosterone levels and reduced CHF risk in individuals over 50 years old.

Conclusion

Our findings suggest that the serum testosterone level was positively associated with CHF in adult males. This study highlights the potential role of serum testosterone in cardiovascular health, particularly in older individuals. Further research is needed to elucidate the underlying mechanisms and explore the clinical implications of these findings.
A study of recurrent life-threatening thrombosis accompanied with the duplication of the factor IX gene
Authors: Wei Xuqian , Zhang Houliang , Chen Weibin , Zhang Jian , Dai Jing
Published: January 2024

Hereditary predisposition play an important role in thrombosis, especially in younger patients. Here we studied a young patient who experienced three different episodes of severe thromboses, some of which were life-threatening (pulmonary artery thrombosis, portal and mesenteric vein thrombosis, and arterial thrombosis of the lower leg). Blood levels of clotting related indicators were assessed. We screened 35 genes linked to thrombosis. We discovered a 756 kb duplication that spanned the F9 gene in region q27.1 of the X chromosome. The repeat includes the full F9 gene, thus, the patient had two functional copies of FIX with the FIX activity 192%. An identical repetition was found in the patient’s mother. Both the patient and his mother had high, but variable, plasma FIX activities that promote coagulation. The patient’s frequent, severe thrombolic events maybe attributed to the duplication of a big portion of the F9 gene and lupus anticoagulant positive.
Interplay of oxidative stress, cellular communication and signaling pathways in cancer
Authors: Iqbal Muhammad Javed , Kabeer Ayesha , Abbas Zaighum , Siddiqui Hamid Anees , Calina Daniela , Sharifi-Rad Javad , Cho William C.
Published: January 2024

Cancer remains a significant global public health concern, with increasing incidence and mortality rates worldwide. Oxidative stress, characterized by the production of reactive oxygen species (ROS) within cells, plays a critical role in the development of cancer by affecting genomic stability and signaling pathways within the cellular microenvironment. Elevated levels of ROS disrupt cellular homeostasis and contribute to the loss of normal cellular functions, which are associated with the initiation and progression of various types of cancer. In this review, we have focused on elucidating the downstream signaling pathways that are influenced by oxidative stress and contribute to carcinogenesis. These pathways include p53, Keap1-NRF2, RB1, p21, APC, tumor suppressor genes, and cell type transitions. Dysregulation of these pathways can lead to uncontrolled cell growth, impaired DNA repair mechanisms, and evasion of cell death, all of which are hallmark features of cancer development. Therapeutic strategies aimed at targeting oxidative stress have emerged as a critical area of investigation for molecular biologists. The objective is to limit the response time of various types of cancer, including liver, breast, prostate, ovarian, and lung cancers. By modulating the redox balance and restoring cellular homeostasis, it may be possible to mitigate the damaging effects of oxidative stress and enhance the efficacy of cancer treatments. The development of targeted therapies and interventions that specifically address the impact of oxidative stress on cancer initiation and progression holds great promise in improving patient outcomes. These approaches may include antioxidant-based treatments, redox-modulating agents, and interventions that restore normal cellular function and signaling pathways affected by oxidative stress. In summary, understanding the role of oxidative stress in carcinogenesis and targeting this process through therapeutic interventions are of utmost importance in combating various types of cancer. Further research is needed to unravel the complex mechanisms underlying oxidative stress-related pathways and to develop effective strategies that can be translated into clinical applications for the management and treatment of cancer.
Predictors of fibrogenesis in children with JIA: a single-center pilot study
Authors: Pavlova Olga , Shevchenko Natalia , Pavlov Sergey , Holovko Tetiana , Bogmat Liudmyla
Published: January 2024

Background

Patients with rheumatological diseases are at high risk of developing irreversible fibrotic changes, both articular and extra-articular, as a result of tissue damage caused by the chronic phase of persistent inflammation. Thus, our purpose was to study early markers of fibrosis formation in children with juvenile idiopathic arthritis (JIA).

Methods

Seventy patients with juvenile idiopathic arthritis, namely, polyarthritis (64.29%) and oligoarthritis (35.71%) variant JIA (mean age 13.3 years, 64.29% girls, 35.71% boys), were included in this 4-year prospective study. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels were determined by ELISA kits.

Results

We evaluated bFGF (mean: 7478.21 pg/ml; min: 4171.56 pg/ml; max: 18,011.25 pg/ml) and VEGF (mean: 342.47 pg/ml; min: 23.68 pg/ml; max: 2158.91 pg/ml) levels in children with JIA. Children with JIA had a higher VEGF level when JIA onset occurred after 15 years of age and they had a high disease activity; additionally, a higher bFGF level was observed in children older than 14 years and in those with a JIA onset after 15 years of age, the oligoarticular variant, a moderate disease activity and regardless of MTX administration but more often when MTX was administered at a dosage from 10 to 12.5 mg/m2/week.

Conclusions

Laboratory screening of fibrosis formation predictors could help identify patients who may be at greater risk of adverse outcomes. Children with JIA had higher bFGF and VEGF levels when JIA onset occurred after 15 years of age, depending on disease activity.
Methotrexate inhibits BMP4 and abrogates the hypertrophic chondrocyte phenotype of synovial fibroblasts in juvenile idiopathic arthritis
Authors: Simonds Megan M. , Freer Samuel T. , Brescia Anne Marie C.
Published: January 2024

Background

Juvenile Idiopathic Arthritis (JIA) induces growth disturbances in affected joints. Fibroblast-like synoviocytes (FLS) play a crucial role in JIA pathogenesis. FLS overexpress bone morphogenetic protein 4 (BMP4) and have a chondrocyte-like phenotype. FLS contribute directly to joint growth disturbances through endochondral bone formation. We investigated the ability of methotrexate to inhibit BMP4 expression and alter the hypertrophic chondrocyte-like phenotype of JIA FLS.

Methods

We selected primary cells from three subjects with persistent oligoarticular JIA, three subjects who eventually extended to a polyarticular disease course, which we termed extended-to-be (ETB), and three subjects who had polyarticular arthritis at time of diagnosis. We treated cells with methotrexate and two BMP4 inhibitors: noggin and chordin. We measured protein concentration from three chondrocyte cell markers: collagen II, aggrecan, and collagen X as well as BMP4.

Results

ColX, marker of chondrocyte hypertrophy, was significantly increased in polyarticular FLS when compared to both persistent FLS and ETB FLS, making polyarticular FLS the most like hypertrophic chondrocytes. Methotrexate caused significant decreases in BMP4 and ColX expression in persistent, ETB, and polyarticular FLS when compared to respective untreated cells. Ligand-binding BMP4 antagonists, noggin and chordin, caused significant decreases in ColX expression in FLS from all three disease courses and significant increases in collagen II protein, an early chondrocyte marker, when compared to respective untreated cells.

Conclusions

Methotrexate, the first-line therapy in the treatment of JIA, mimics BMP4 antagonists by effectively lowering BMP4 and ColX expression in FLS. Inhibiting FLS from undergoing hypertrophy could prevent these cells from contributing to joint growth disturbances via endochondral bone formation.
A rare case of coronary artery complication in a child with systemic juvenile idiopathic arthritis and macrophage activation syndrome: case report and literature review
Authors: Zhang Lian , Wei Yanwen , Zeng Ningjing , Wang Lianyu , Chen Xinying , Yang Jinghua , Xiao Xiaolan
Published: January 2024

A rare case of coronary artery involvement in a child with Systemic Juvenile Idiopathic Arthritis (sJIA) complicated by Macrophage Activation Syndrome (MAS) is reported. The patient initially received an inaccurate diagnosis of Kawasaki Disease, sepsis, and mycoplasma infection and showed no improvement after Intravenous Immune Globulin (IVIG) treatment. Upon admission, symptoms included diffuse red rash, swelling of the limbs, lymph node enlargement, and hepatosplenomegaly. Post investigations, a diagnosis of sJIA and MAS was confirmed, and treatment involved a combination of hormones (methylprednisolone) and immunosuppressive drugs (methotrexate). The revealed widened coronary artery diameter was managed with a disease-specific treatment plan and prophylactic plus low-dose aspirin anti-coagulation therapy. Under this management, MAS was well controlled, and follow-ups showed normalization of the child’s coronary artery structure and function. This case and the associated literature review underscore the importance of early recognition, diagnosis, treatment, and long-term monitoring for children presenting with sJIA and MAS complicated by coronary artery involvement.
Effect of probiotic supplementation on lipoprotein-associated phospholipase A2 in type 2 diabetic patients: a randomized double blind clinical controlled trial
Authors: Jaff Salman , Gubari Mohammed , Shab-Bidar Sakineh , Djafarian Kurosh
Published: January 2024

Background

It has been recently reported that lipoprotein-associated phospholipase A2 (Lp-PLA2) may predict the risk of cardiovascular disease. The effect of multi-strain probiotics on Lp-PLA2 in patients with type 2 diabetes is still not clear.

Aims

This study aimed to determine the effect of multi-strain probiotic supplementation on lipoprotein-associated phospholipase A2, and glycemic status, lipid profile, and body composition in patients with type 2 diabetes.

Methods

In this randomized double-blind placebo-controlled clinical trial, 68 participants with type 2 diabetes, in the age group of 50–65 years, were recruited and randomly allocated to take either probiotic (n = 34) or placebo (n = 34) for 12 weeks. The primary outcome was lipoprotein-associated phospholipase A2, and secondary outcomes were glycemic parameters, lipid profile, anthropometric characters, and body composition (fat mass and fat-free mass).

Results

There was a significant reduction in serum lipoprotein-associated phospholipase A2, in the probiotic group, it dropped by 6.4 units at the end of the study (p < 0.001) compared to the placebo group. Probiotic supplementation also resulted in a significant improvement in the hemoglobin A1c and high-density lipoprotein cholesterol 1.5% (p < 0.001) and 6 mg/dl (p 0.005), respectively. There were no significant changes in other outcomes.

Conclusion

Probiotic supplementation was beneficial for reducing Lp-PLA2 and hemoglobin-A1c and improving high-density lipoprotein cholesterol, which may suggest an improvement in the prognosis in patients with type 2 diabetes.
HIV/AIDS, SARS, and COVID-19: the trajectory of China’s pandemic responses and its changing politics in a contested world
Authors: Zhou Yanqiu Rachel
Published: January 2024

The COVID-19 pandemic has revealed the contested politics of global health governance, though we still don’t know enough about the dynamics of domestic pandemic responses, or about the relationship between the politics of those responses and the politics of global health governance, both of which have changed significantly in recent decades. Focusing on three cases (HIV/AIDS, SARS, and COVID-19) of cross-border infectious diseases, this article explores the trajectory of China’s pandemic responses in the context of globalization. Attending to changing politics at domestic, international, and global levels, I argue that those responses have been a complex combination of China’s domestic politics (e.g., priorities, institutions, leadership, and timing), its international relations (especially with the US), and its engagements with global health governance. It is concluded that the increasing divergence of pandemic responses in a time of ubiquitous global health crisis demands urgent attention to the connections (including contestations) between domestic pandemic responses and the evolvement of global health governance from a broader perspective that considers changes in geopolitics.
Cluster-randomized implementation trial of two facilitation strategies to implement a novel information and communications technology at the Veterans Health Administration
Authors: Leonard Chelsea , Carey Evan , Holstein Ariel , Ho P. Michael , Heckman Jeffrey T.
Published: January 2024

Background

Information and communication technologies (ICTs) improve quality and efficiency of healthcare, but effective practices for implementing new ICTs are unknown. From 2019 to 2021, the Veterans Health Administration (VHA) implemented FLOW3, an ICT that facilitates prosthetic limb care. The goal of this study was to compare the impact of two facilitation strategies on FLOW3 adoption, implementation, and sustainment.

Methods

FLOW3 is a computerized workflow management system comprised of three applications that facilitate the three steps for prosthesis authorization. During VHA’s implementation of FLOW3, we randomized 60 VHA sites to basic or enhanced facilitation groups. Basic facilitation included a manualized training toolkit and office hours. Enhanced facilitation included basic facilitation plus monthly learning collaboratives and site-specific performance reports. Outcomes included time to adoption of FLOW3 and complete FLOW3 utilization rates during implementation and sustainment periods. We compared outcomes between sites assigned to basic versus enhanced facilitation groups. Results were calculated using both intent-to-treat (ITT) and dose–response analyses. The dose–response analysis used a per-protocol approach and required sites in the enhanced facilitation group to join two of six learning collaboratives; sites that attended fewer were reassigned to the basic group.

Results

Randomization assigned 30 sites to enhanced facilitation and 30 to basic. Eighteen of 30 randomized sites were included in the enhanced facilitation group for dose–response analysis. During the implementation period, enhanced facilitation sites were significantly more likely to completely utilize FLOW3 than basic facilitation sites (HR: 0.17; 95%CI: 1.18, 4.53,p = 0.02) based on ITT analysis. In the dose–response analysis, the enhanced group was 2.32 (95%CI: 1.18, 4.53) times more likely to adopt FLOW3 than basic group (p = 0.014).

Conclusions

Enhanced facilitation including a learning collaborative and customized feedback demonstrated greater likelihood for sites to complete a prosthetics consult using FLOW3 throughout our study. We identified statistically significant differences in likelihood of adoption using the dose–response analysis and complete utilization rate using ITT analysis during the implementation period. All sites that implemented FLOW3 demonstrated improvement in completion rate during the sustainment period, but the difference between facilitation groups was not statistically significant. Further study to understand sustainability is warranted.