bluuebunny/crossref_metadata_2025 huggingface dataset:
CHK2 immunohistochemical expression in prostatic carcinoma of Egyptian patients
Authors: El-Rebey Hala Said , Hola Ayat Shawky Abo , Kora Mona Abdelhamid , Alagizy Hagar , Hassanin Rania Abdallah
Published: October 2024

Background: Prostatic carcinoma (PCa) is a diverse disease with a complex molecular landscape that evolves throughout disease progression. There is a great need for novel biomarkers that are more effective at predicting PCa outcomes. CHK2 is a tumor suppressor gene and is considered a prospective target for prognostic and therapeutic applications. This study aims to investigate the immunohistochemical expression of CHK2 in PCa patients and to correlate its expression with the studied clinicopathological parameters, including survival data.
Material and Methods:
CHK2 expression was detected via immunohistochemistry in 71 biopsies from PCa patients and 34 biopsies from patients with nodular prostatic hyperplasia (NPH). CHK2 reactivity (positive vs negative) together with the total percentage of positive cells and H score were estimated in both studied groups.
Results: CHK2 immunoexpression was significantly greater in PCa patients than in NPH patients in terms of reactivity and H score (P= 0.036 and P= 0.018, respectively). PCa patients with high-grade PIN foci presented significantly lower total CHK2 expression (P=0.04). Univariate overall survival (OS) and progression-free survival (PFS) analyses revealed no significant differences according to CHK2 reactivity or total percent expression.
Conclusion: Our findings validated the importance of CHK2 in the mechanism of neoplastic transformation of the prostate.
Impact of age on surgical outcomes for World Federation of Neurosurgical Societies grade I and II aneurysmal subarachnoid haemorrhage: a novel prognostic model using recursive partitioning analysis
Authors: Umekawa Motoyuki , Yoshikawa Gakushi
Published: October 2024

Objective
This study aimed to evaluate age as a prognostic factor and develop a comprehensive prognostic model for patients undergoing clipping surgery for World Federation of Neurosurgical Societies (WFNS) grade I/II aneurysmal subarachnoid haemorrhage (SAH).
Methods
We retrospectively investigated 188 patients with WFNS grade I/II SAH who underwent microsurgical clipping at our institute between December 2010 and January 2020. The data of 176 patients (75 with grade I and 101 with grade II) were analysed. Data on patient demographics, aneurysm characteristics, SAH factors, surgical details, and clinical outcomes were collected. Prognostic factors were assessed using bivariate and multivariable logistic regression analyses, and recursive partitioning analysis.
Results
Favourable outcomes (mRS 0–2) were observed in 76% of patients. Age, a significant negative prognostic factor in multivariable analysis (odds ratio 0.55, 95% confidence interval 0.40–0.76, p < 0.001), was cutoff at 70 years by the receiver operating characteristic curve. Patients aged ≤ 70 years had significantly better outcomes than those aged > 70 years (84% vs. 46%, respectively; p < 0.001). Epileptic seizures were significantly associated with poor outcomes in older adults (p < 0.001). A prognostic model (favourable, intermediate, and poor) based on age and postoperative adverse events showed significantly different outcomes between age groups (p < 0.001).
Conclusions
Age was a stronger prognostic factor than WFNS grading for patients with grade I/II SAH undergoing microsurgical clipping. For patients aged ≤ 70 years, precise microsurgeries with fewer complications were associated with favourable outcomes beyond WFNS grade. For older patients, postoperative intensive seizure management may prevent poor outcomes.
Belumosudil for the Treatment of Chronic Graft-versus-Host Disease: A Single Center Real-World Experience
Authors: Salhotra Amandeep , Modi Badri , Ngo Dat , Chen Jason , Yang Dongyun , Shan Hayoue , Sandhu Karamjeet , Nashid Rahid , Amanam Idoroenyi , Otoukesh Salman , Nakamura Ryotaro , Ali Haris
Published: October 2024

Chronic graft-versus host disease (cGVHD) remains a major complication post-allogeneic stem cell transplantation (HCT). Belumosudil, a ROCK2 inhibitor was approved for cGVHD with 2–5 prior lines of therapy. We retrospectively analyzed 45 patients who received belumosudil at City of Hope Medical Center. Prior to belumosudil, the median age was 59 yrs with 3 prior lines of therapy (range 1–6). GVHD severity was predominantly moderate (37.8%) and severe (46.7%). Many patients had a prior history of ruxolitinib (71.1%), with concurrent use of belumosudil occurring in 51.1% of patients. ORR at 6-months and 12 months were 31.1% and 33.4% respectively. The best ORR at any point during belumosudil was 46.7% (CR 6.7% + PR 40%) and median FFS was 11.2 months. Infection occurred in 42% of patients, with 27% of patients requiring hospitalization to manage infection. Patients with concurrent ruxolitinib had higher infection rates (60.9% vs. 22;7%, p = 0.0156) and hospitalization (47.8% vs. 4.5%, p = 0.0017). Most infections were viral and considered mild requiring no hospitalization to manage the infection. Real-world experience with belumosudil supports the use in the treatment of cGVHD based on the ORR, promising FFS, and good tolerability in patients who have progressed on multiple prior lines of therapy.
Investigating the metabolite-mediated effects of immune cells on squamous lung cancer: a Mendelian randomization analysis
Authors: Qu HongPeng , Zhou Min , Guo QuanMin , Qiu Yanjun
Published: October 2024

Background
Lung cancer (LC) is a leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) being a significant subtype. Immune cells are critical in tumor surveillance and the immune response, and recent advancements in immune checkpoint inhibitors (ICIs) have enhanced the treatment of non-small cell lung cancer (NSCLC), including LUSC. Metabolites produced during tumor metabolism may influence immune cell function, affecting immune cell proliferation, differentiation, and activation and overall effectiveness. This study aims to explore the causal relationships between metabolite-mediated immune cells and LUSC via Mendelian randomization (MR).
Methods
Genome-wide association study (GWAS) summary statistics for LUSC were obtained from the International Lung Cancer Consortium (ILCCO), including 3,275 cases and 15,038 controls, with data on 8,893,750 single nucleotide polymorphisms (SNPs). A total of 731 immunophenotypes and 1,400 metabolite GWAS catalogs were analyzed. The study conducted four MR analyses: forward MR analysis with immune cells as the exposure and LUSC as the outcome, positive MR analysis with metabolites as the exposure and LUSC as the outcome, and mediated MR analysis with immune cells as the exposure, metabolites as mediators, and LUSC as the outcome. Sensitivity analyses were performed to ensure the robustness, heterogeneity, and multibiological effects of the findings.
Results
The analysis revealed that 13 immune cells, including 7 high-risk immune cells and 6 protective immune cells, were significantly correlated with LUSC. Thirteen metabolites were also linked to LUSC, with 2 high-risk and 11 protective metabolites. Mediated MR analysis revealed significant associations between naive-mature B-cell percentage and taurolithocholate 3-sulfate (mediated effect = 0.006, p = 0.0405), the CD4/CD8br ratio and the alpha-ketoglutarate to aspartate ratio (mediated effect = 0.023, p = 0.0121), and the CD4 + percentage of leukocytes and SSC-A on lymphocytes with indolepropionate levels (mediated effect = 0.018, p = 0.0169 and mediated effect=-0.017, p = 0.0162, respectively).
Conclusion
This study reveals the causal roles of immune cells and metabolites in LUSC via genetic approaches. These findings suggest that specific metabolites mediate the involvement of immune cells in LUSC, providing new insights for therapeutic strategies.
Robustness Assessment of Regressions using Cluster Analysis Typologies: A Bootstrap Procedure with Application in State Sequence Analysis
Authors: Roth Leonard , Studer Matthias , Antille Emilie , Peytremann-Bridevaux Isabelle
Published: October 2024

Background
In standard Sequence Analysis, similar trajectories are clustered together to create a typology of trajectories, which is then often used to evaluate the association between sequence patterns and covariates inside regression models. The sampling uncertainty, which affects both the derivation of the typology and the associated regressions, is typically ignored in this analysis, an oversight that may lead to wrong statistical conclusions. We propose utilising sampling variation to derive new estimates that further inform on the association of interest.
Methods
We introduce a novel procedure to assess the robustness of regression results obtained from the standard analysis. Bootstrap samples are drawn from the data, and for each bootstrap, a new typology replicating the original one is constructed, followed by the estimation of the corresponding regression models. The bootstrap estimates are then combined using a multilevel modelling framework that mimics a meta-analysis. The fitted values from this multilevel model allow to account for the sampling uncertainty in the inferential analysis. We illustrate the methodology by applying it to the study of healthcare utilisation trajectories in a Swiss cohort of diabetic patients.
Results
The procedure provides robust estimates for an association of interest, along with 95% prediction intervals, representing the range of expected values if the clustering and associated regressions were performed on a new sample from the same underlying distribution. It also identifies central and borderline trajectories within each cluster. Regarding the illustrative application, while there was evidence of an association between regular lipid testing and subsequent healthcare utilisation patterns in the original analysis, this is not supported in the robustness assessment.
Conclusions
Investigating the relationship between trajectory patterns and covariates is of interest in many situations. However, it is a challenging task with potential pitfalls. Our Robustness Assessment of Regression using Cluster Analysis Typologies (RARCAT) may assist in ensuring the robustness of such association studies. The method is applicable wherever clustering is combined with regression analysis, so its relevance goes beyond State Sequence Analysis.
Factors Affecting Time to Recovery From Diabetic Ketoacidosis in Adult Diabetic Patients in Alexandria Main University Hospital
Authors: Sabry Ahmed A. , Alkafafy Asmaa Mohamed , Morsy Eman Youssef , Aiad Ahmed , Montasser Mina
Published: October 2024

Background
Diabetic ketoacidosis (DKA) is a life-threatening condition as a complication of diabetes and represents a significant healthcare global burden. The current study goal was to determine factors affecting time to recovery from DKA in Alexandria Main University Hospital.
Patients and methods:
150 patients who had been admitted with DKA were included in this study. All patients were managed with hospitalization for IV fluids, continuous intravenous insulin infusion, electrolytes correction, as well as detection and treatment of the predisposing factor until the full resolution of DKA.
Results
Males contributed to (58.7%) of the total patients in this study with a mean age of (32.16 ± 15.06) years. DKA mean time of resolution was (18.76 ± 14.07) hours. The majority of patients were with T1DM (86%), while T2DM were (14%). Missed insulin dose was the leading precipitating factor (60.7%) followed by infections (38.7%). There was a statistically significant relationship between DKA resolution time with age, time of presentation, type of diabetes, initial PH, initial serum K+ level, initial HCO3− level, initial anion gap, initial base excess, and initial RBS. (p value < 0.001).
Conclusion
Delayed time of resolution from DKA was associated with initial lower PH, initial lower HCO3− level, initial lower base excess level, initial higher anion gap level, type 2 diabetes mellitus, patients on pre-mixed insulin regimen, old patients, delayed time for seeking medical care, and abnormal serum K+ level.
Caries and obesity: A cross-sectional study of populations and microbiology
Authors: Chen Bai-Ru , Yang Xiao-Peng , Yang Wei , Ma Nan , Wang Meng , Li Yi-Min , Bao Mei-Hua , Wang Cheng-Yue
Published: October 2024

Caries and obesity in children are public health concerns. Although the relationship between the two non-communicable diseases has been studied for many years, the results are still controversial. This study aimed to investigate the relationship between caries and obesity in children aged 7-12 years old in Jinzhou, China.1864 children were selected for cluster sampling clinical study. All the selected students completed a questionnaire, recorded their height and weight, conducted oral examinations, and collected decayed⁃missing⁃filled teeth (dmft , DMFT) information. Forty children were randomly divided into the following groups: high caries (HC) + obese, caries-free (CF) + obese, HC+non-obese (NO), CF+NO. The diagnosis of dental caries and obesity is based on the standards of the World Health Organization. Collect saliva and feces samples. Multivariate analysis of variance, chi-square test, and multiple linear regression were used to evaluate the data, and 16s rDNA V3-V4 was used to detect microorganisms in saliva and fecal samples. The prevalence rates of dental caries, overweight, and obesity were determined, with significant associations found between demographic factors and BMI. Factors such as dietary structure, frequency of specific food consumption, parents' educational level, exercise habits, and sedentary behavior were linked to the decayed-missing-filled index of teeth. Microbiota analysis revealed differences in microbial composition between caries and non-caries, obese and non-obese groups in both saliva and feces samples. Dietary factors, particularly the consumption of sugary foods, along with exercise frequency, sedentary behaviors, and parental educational levels, are recognized as common risk factors for caries and obesity. Notably, the prevalence of caries in primary teeth is inversely correlated with BMI, whereas the rate of caries in permanent teeth is directly proportional to BMI.16S rDNA sequencing results suggesting that prevotella may act as a co-pathogenic bacterium in the development of both conditions.
Outcomes of Hematopoietic Cell Transplantation in Children with Inborn Errors of Immunity
Authors: Hashem Hasan , Ghatasheh Lubna , Najjar Rula , Mufarrej Duaa , Zandaki Duaa , Shanap Mayada Abu , Khattab Eman , Rihani Rawad , Sultan Iyad
Published: October 2024

Inborn errors of immunity (IEI) are a heterogenous group of rare monogenic disorders that affect innate or adaptive immunity, resulting in susceptibility to life-threatening infections and autoimmunity. Allogeneic hematopoietic cell transplantation (HCT) is a valuable curative option for children with IEI. We conducted a retrospective single-center study on the outcome of HCT in children with IEI. Primary outcome was overall survival (OS). We gathered data from 55 patients underwent HCT in the period 2014 to 2023. The indications for HCT were CGD (n = 14), HLH (n = 12), SCID (n = 10), and others (n = 19). Median age at HCT was 3 years (range 0.1–17). Donors were HLA-matched related (n = 27), haploidentical (n = 24), and cord (n = 4). The conditioning regimens were myeloablative (n = 34), reduced intensity (n = 18), or no conditioning (n = 3). After a median follow-up of 43 months (range 13–120), 2-year OS was 93%, 2-year EFS 79% and 2 year GvHD-free relapse-free survival (GRFS) was 69%. Univariate analysis showed that bone marrow source was significantly associated with better EFS and GRFS. Cumulative incidence of grade 2–4 acute and moderate/severe chronic GvHD were 21% and 13%, respectively. Incidence of graft failure was 13%. In conclusion, HCT is feasible and curative in children with IEI. Early diagnosis and referral in addition to timely treatment can further improve outcomes.
From arteries to age: an intrinsic impact of Circle of Willis on first-ever acute ischemic stroke in the oldest-old
Authors: Jiao Shusheng , Zhi Jianxia , Li Miaomiao , Chen Liping , Gong Zihua , Ma Haoyuan , Wang Qinghua , Cheng Xiaofang
Published: October 2024

Background: This study aimed to describe the characteristics of CoW configuration in the oldest-old patients with first-ever acute ischemic stroke, and investigate the association of CoW with the first-onset age of acute ischemic stroke in the elderly population.
Methods: The patients with first-ever acute ischemic stroke were consecutively enrolled between March 2022 and June 2024. All patients underwent MRA or CTA of brain. According to their first-onset age, they were divided into two groups (oldest-old group, aged ≥80 years; elderly group, aged 60-79 years). Demographic and clinical data were collected, and CoW scores and types were independently assessed by two experienced neurologists.
Results: The oldest-old group showed greater Anterior communicating artery (AcoA) and total CoW scores and a higher ratio of complete CoW as compared with the elderly group. Poor CoW was associated with earlier first-onset age, and higher AcoA score was associated with later first-onset age, even after adjustments by conventional risk factors. In the female cohort, the oldest-old subset showed high scores of AcoA, Posterior communicating artery (PcoA) and total CoW, with all difference strength significantly greater than those in all subjects. Additionally, in the female cohort, first-onset age was significantly related with AcoA score, total CoW score and poor CoW, whether non-adjusted or adjusted.
Conclusions: The oldest-old patients with first-onset ischemic stroke have a higher CoW score and better morphology than the elderly patients, with females more significant. Females with poor CoW should be recommended for risk stratification of ischemic stroke to generate more effective and precise strategies for stroke prevention and healthy aging.
Evaluation of pharyngeal airway volume and soft tissue changes after bimaxillary orthognathic surgery in skeletal class III patients using CBCT: Long-term Study
Authors: Hashemi Seyedeh Zahra , Torkzadeh Azadeh , Ghaffari Roshanak , Momeni Hasan , Aryanezhad Seyed Sasan , Arianezhad S. Marjan
Published: October 2024

Background
Bimaxillary surgery is increasingly used to correct Class III malocclusion, but concerns about potential airway narrowing and its role in obstructive sleep apnea (OSA) remain. This study aimed to evaluate the long-term effects of bimaxillary surgery on the upper airway and posterior soft tissues in skeletal Class III patients using Cone Beam Computed Tomography (CBCT).
Methods
In this retrospective descriptive-analytical study, fifty female patients (mean age, 35.17 ± 9.16 years) with mandibular prognathism were treated with LeFort I advancement nad bilateral sagittal split osteotomy. They all had under two score of STOP-BANG questionnaire. CBCT were performed before surgery and 5 years after surgery with standardized head and neck positioning. Airway volume and posterior soft tissue were analyzed using OnDemand 3D software version 10.0.1. Data were analyzed using independent t-tests, Pearson's correlation, and chi-square.
Results
in the long term, bimaxillary surgery statistically significantly increased the nasopharyngeal volume by 14.06% (P = 0.015) and decreased hypopharyngeal and upper airway volumes by 20.13% and 7.71% (P = 0.000, 0.015), respectively. Although there was a decrease in the oropharyngeal volume and the position of the soft palate, the changes were not statistically significant. The tongue moved backward by undergoing bimaxillary surgery (P = 0.005). No significant differences in STOP-BANG scores were observed.
Conclusions
Although bimaxillary surgery significantly reduces airway volume parameters, it does not elevate the risk of OSA in normal subjects. Our results can aid orthodontists and oral surgeons in selecting the proper surgical method.
Preoperative neutrophil-lymphocyte and lymphocyte-monocyte ratios predict prognosis in patients with penile cancer undergoing partial or total penectomy
Authors: Song Xin , Peng Xingshun , Li Yang , Jiao Yubo , Cai Zhikang
Published: October 2024

Purpose
To investigate the prognostic values of preoperative neutrophil–lymphocyte ratio (NLR)and lymphocyte–monocyte ratio (LMR) in patients with penile squamous cell carcinoma (PSCC).
Methods
A total of 47 patients with PSCC who underwent partial or total penectomy from 2000 to 2022 was retrospectively analyzed. The receiver operating characteristic(ROC) curves were used to determine the cutoff values of NLR and LMR for diagnosis of tumor recurrence. Kaplan–Meier method and log-rank test were used in the survival analysis. Cox proportional-hazards regression model was used in the independent risk factor analysis.
Results
The cutoff values of NLR and PLR derived from the ROC curves were 2.3 and 3.9 respectively. Univariate analysis revealed that NLR and LMR were significantly associated with PFS (P < 0.001, P = 0.029). Lymph node metastasis (P < 0.001 and P < 0.001), distant metastases (P = 0.001 and P = 0.001) and pathological stage (P = 0.001 and P < 0.001) correlate significantly with PFS and OS, respectively. Multivariate analysis verified pathological stage, lymph node metastasis, and NLR to be independent prognostic factors for PFS (P = 0.021, P = 0.001 and P = 0.033).
Conclusions
NLR could be an independent predictor of PFS in patients with PSCC.
Establishment and Internal Validation of a Model to Predict the Efficacy of Adalimumab in Crohn's Disease
Authors: Wang Fang , Wu Tong , Zhou He , Liang Jie , Zhang Yujie , Shi Yanting , Zhang Tiantian , Da Yu
Published: October 2024

Background
Clinically, the ability to distinguish which Crohn's Disease patients can benefit from Adalimumab is limited.
Aims
This study aimed to develop a model for predicting clinical remission probability for Crohn's disease patients with Adalimumab at 12 weeks.
Methods
Demographic and clinical characteristics of Crohn's disease patients were utilized to develop a model for clinical remission probability. The discriminatory and calibrating ability of the model and the internal validation were determined.
Results
68 patients with Crohn's disease were enrolled in this study. Clinical remission was observed in 55.9% at 12 weeks. Three variables were selected through the least absolute shrinkage and selection operator regression method, including Adalimumab-positive cell count, disease duration, and neutrophil count of Crohn's disease patients. A predictive model was constructed by multivariate logistic regression (Adalimumab-positive cell count (OR, 1.143; 95%CI, 1.056–1.261), disease duration (OR, 0.967; 95%CI, 0.937–0.986), and neutrophil count (×109/L) (OR, 1.274; 95%CI,1.014–1.734)). The predictive model yielded an area under the curve of 0.866 (95%CI, 0.776–0.956), and in the internal validation, the area under the curve was 0.870 (95%CI, 0.770–0.940).
Conclusions
The predicting model is of great value for predicting clinical remission probability in Crohn's disease patients with Adalimumab therapies.
The Effect of Empowerment Program on the Pain Control and Self-Efficacy in Patients Under Total Knee Arthroplasty in Iran
Authors: Ghahramanian Akram , Mirmaroofi Nazila , Asghari-Jafarabadi Mohammad , Behshid Mozhgan , Tabrizi Faranak Jabbarzadeh , Onyeka Tonia , Ganjpour Jafar
Published: October 2024

Background
Knee osteoarthritis is associated with significant limitations in range of motion. Therefore, improvement of pain and self-efficacy indices are very important. This study aimed to examine the effects of an empowerment program on the improvement of self-efficacy and pain control in patients with total knee arthroplasty (TKA).
Methods
A quasi-experimental design was used. Control group (n = 49) received routine care, whereas the intervention group (n = 49) received an empowerment program in addition to routine care, based on Linton’s cognitive-behavioral model and Bandura's self-efficacy theory. Before and after intervention, pain and self-efficacy were measured using the short form-McGill Pain Questionnaire and pain self-efficacy questionnaire respectively.
Results
A between group comparison demonstrated significant differences in pain subscales, including sensory-affective components (Mean Difference = 1.8, 95% CI= [-3.86 to -0.96], p = 0.015), PPI (0.62, [-0.18 to -1.04], 0.023), and VAS (1.57, [1.01 to -2.12], < 0.001), indicating superior outcomes in the intervention group. Notably, there was a substantial between-groups disparity in terms of pain self-efficacy (9.81, [0.71 to 1.24], < 0.001). After adjustment using ANCOVA, the results persisted.
Conclusion
Considering the effectiveness of the empowerment program used in this study as an interactive, applicable, and non-invasive approach, it can be used to increase pain management and self-efficacy of patients undergoing TKA treatment.
Clinical Symptom Influence on The Time of Nucleic Acid Conversion to Negative in COVID-19 Patients with SARS-CoV-2 Omicron Variant: A Retrospective Observational Study
Authors: Feng Hui , Hong Xiang , Qiu Shanhu , Ma Shaolei , Huang Yingzi
Published: October 2024

Background
The duration for COVID-19 patients to achieve a negative nucleic acid test result is influenced by various factors. This study aimed to explore the influences of clinical symptoms of COVID-19 on the time required for nucleic acid test results to become negative.
Methods
This retrospective study enrolled a total of 486 participants infected with COVID-19 who were aged ≥ 18 years and hospitalized at Shanghai Lingang Make-shift Hospital between April 10, 2022, and May 20, 2022. The clinical data included patient demographics, clinical symptoms, and the time of nucleic acid conversion to negative, all assessed using a cross-sectional study method.
Results
This study included COVID-19 patients with a median age of 38, comprising 66.0% males and 34.0% females. Multiple linear regression analyses demonstrated a significant positive correlation between the time of nucleic acid conversion to negative and the clinical symptoms of throat pain among patients with COVID-19 (β = 0.845, 95% CI: 0.123–1.567, P ≤ 0.05). Logistic regression analysis showed that throat pain had a significant negative effect on the 7-day negative nucleic acid conversion rate (OR = 0.586, 95%CI:0.390–0.880, P ≤ 0.01), as did diarrhea(OR = 0.541, 95%CI = 0.295–0.989, P ≤ 0.05).
Conclusion
The varying clinical symptoms influence the time to negative nucleic acid test results in COVID-19 patients, indicating that these symptoms should receive special attention in clinical treatment to optimize therapy and shorten recovery time.
Potential blood biomarkers to differentiate ischemic and hemorrhagic strokes
Authors: Song Jinhui , Yu Danhua , Zhou Jinli , Chen Weiwei , Qi Dongwang
Published: October 2024

Background
Currently, besides neuroimaging, there is a lack of alternative methods for rapid differentiation of ischemic stroke (IS) and intracerebral hemorrhage (ICH), which significantly impacts the timely treatment of patients. This study aims to elucidate the causal relationship between circulating metabolites and susceptibility to IS and ICH.
Methods
A two-sample Mendelian Randomization (MR) analysis was performed to estimate the causality of metabolites and metabolite ratios on IS/ICH. For exposure data, we extracted genetic variants associated with 1, 091 plasma metabolites and 309 metabolite ratios traits from the Canadian Longitudinal Study on Aging (CLSA) cohort (n = 8, 299). For outcomes, we selected IS and its three subtypes including cardioembolic stroke (CES), small vessel stroke (SVS), and large artery (LAS) from the latest stroke genome-wide association studies (GWAS) database (73, 652 patients). In addition, we have included ICH as a primary outcome (n = 1, 545 cases).
Results
In this MR analysis, there were 115, 105, 89, 70, and 48 plasma metabolites or metabolite ratios suggestive associated with IS, LAS, CES, SVS, and ICH. After false discovery rate (FDR) correction and sensitive analysis, 20 robust causative associations between 16 metabolites (e.g., ribitol, campesterol, and thymol sulfate)/ 4 metabolite ratios and IS or ICH were finally identified. Among them, six metabolites may serve as potential indicators for distinguishing between IS and ICH.
Conclusion
The finding of our study suggested that identified metabolites and metabolite ratios can be considered useful circulating biomarkers for IS and ICH screening and differential diagnosis in clinical practice.
Chronic Rose Oxide and Exercise Synergistically Modulate Cardiovascular and Autonomic Functions in Hypertensive Rats
Authors: Silva Juliana A. da , Araújo Samuel S. P. , Silva Ana Flávia M. da , de Assunção José Guilherme V. , Santos Pâmela S. , Júnior José L. P. , Reis Carlos Eduardo S. , Santana Liana M. , Silva Regina G. , Oliveira Ariell A. , Nunes Francisca V. Sousa , Oliveira Aldeidia P. , Sousa Damião P. , Soriano Renato N. , Branco Luiz G. S. , Salgado Helio C. , Sabino João Paulo Jacob
Published: October 2024

With the alarming rise in cases of arterial hypertension worldwide, there is an urgent need to develop combined therapies to mitigate this scenario. Rose Oxide (RO), a monoterpene with anti-inflammatory and hypotensive properties, emerges as an alternative. The present study is the first to evaluate the effect of RO administered chronically and combined with physical exercise (swimming) since both have been reported to have beneficial impacts on hypertension. Male SHR and Wistar rats (aged 12 weeks) received RO for 34 consecutive days (orally; 100 mg/kg). The progression of systolic blood pressure (SBP) was monitored through tail-cuff plethysmography. Twenty-four hours before the end of the treatment, the animals were anesthetized, and the femoral artery and vein were cannulated to record the pulsatile arterial pressure and to administer drugs, respectively. Hemodynamic and autonomic parameters and baroreflex sensitivity and intrinsic heart rate (IHR) were evaluated. Treatment with RO, administered alone or combined with exercise, reduced SBP and mean arterial pressure in SHR. The swimming protocol did not prevent increases in BP, but when combined with RO, it improved autonomic control, assessed through heart rate variability and parasympathetic tone. IHR was attenuated in SHR, and none of the treatments reversed this response. Therefore, combining RO with physical exercise may enhance their antihypertensive effects, improving autonomic function, reducing oxidative stress and inflammation, providing synergistic cardiovascular benefits, improving metabolic health, promoting a comprehensive lifestyle intervention, and potentially allowing for reduced medication dosages. This multifaceted approach could offer a more effective and sustainable strategy for managing hypertension.
Delineation of reduced CTV2 based on the characteristics and distribution of cervical lymph node metastasis in nasopharyngeal carcinoma
Authors: Wang Zhiqiang , Yang Yi , Ge Chunlei , Tian Rui , Cheng Sheng , Gao Jingyu , Wang Yan , Yue Qi , Wang Zhiwei , He Qingqing , Xu Yuchuan , Li Yan , Feng Xudong , Yang Yanli , Zhang Yong
Published: October 2024

Introduction: To accurately locate each metastatic lymph node, identify potential areas for exemption from radiotherapy in patients with NPC, and assess the dosimetric difference in OARs between reduced-target radiotherapy and conventional radiotherapy.
Methods and Materials: A total of 209 patients were included to analyze the pattern and distribution characteristics of cervical lymph node metastasis. Thirty patients with NPC were randomly selected for reduced CTV2 radiotherapy through a lottery system. The variation in doses to the OARs was evaluated in different cohorts.
Results: A total of 2314 metastatic lymph nodes were identified and mapped. There were no metastatic lymph nodes observed at level VIIb and within the lateral border of the common carotid artery. The percentages of metastatic lymph nodes at levels Ⅰa, Ⅰb, Ⅱa, Ⅱb, Ⅲ, Ⅳa, Ⅳb, Ⅴa, Ⅴb, Ⅴc, Ⅵa, Ⅵb, Ⅶa, Ⅶb and Ⅷ accounted for 0%, 1.5%, 22.8%, 41.1%, 15.9%, 3.0%, 0%, 4.4%, 1.0%, 0.3%, 0%, 0%, 9.7%, 0% and 0.3%, respectively, of the 2314 metastatic lymph nodes. Further analysis of dosimetric outcomes revealed a significantly lower mean dose to the oral cavity, laryngeal cavity, esophagus, trachea, pharyngeal constrictor muscles, parotid gland, submandibular gland and thyroid gland with the implementation of reduced-target radiotherapy than with standard radiotherapy.
Conclusion: IMRT sparing level Ⅰa, Ⅰb, Ⅳb, Ⅵ, and Ⅶb lymph nodes and the area within the lateral border of the common carotid artery is feasible in NPC patients.
A multi-omics analysis of CSF reveals the differential immunopathology molecular mechanisms underlying viral encephalitis and autoimmune encephalitis
Authors: Zhu Kun , Lin Ke , Shen Feifei , Zhang Haocheng , Zhang Yi , Deng Bo , Xue Quanlin , Guo Jingxin , Wu Qian , Ai Jingwen , Chen Xiangjun , Zhang Wenhong
Published: October 2024

Background: This study explores viral encephalitis (VE) and autoimmune encephalitis (AE), similar in symptoms but requiring distinct treatments. Early diagnosis is crucial for effective intervention. The research utilizes early cerebrospinal fluid (CSF) analysis, employing transcriptomics, proteomics, and metabolomics to understand the immunological aspects of VE and AE.
Methods: Participants from the IMPROVE clinical trial (ClinicalTrial.gov, NCT04946682, July 1, 2021) between April 2018 and November 2022 were included. CSF samples at disease onset were analyzed for VE and AE immunological profiles.
Results: CSF analysis from 34 VE patients, 29 AE patients, and 6 controls unveiled shared and distinct immune mechanisms. Compared to controls, VE and AE patients showed reduced neuronal transporter functions and increased T and B cell activation. VE exhibited heightened interferon responses, complement pathways, and CD8+ T cell functions. AE displayed unique modulations in CD4+ T cell and Treg cell activities, potentially reducing autoimmune responses. Both conditions induced damage to critical brain areas.
Conclusion: The study identified immunological differences and similarities, emphasizing specific CSF molecular changes for differential diagnosis. Findings highlighted complex immune interactions, with both diseases involving suppressed neuronal functions and heightened T and B cell activities. VE featured distinct interferon and CD8+ T cell activations, while AE showed specialized CD4+ T and Treg cell modulations. Immune balance played a crucial role in encephalitis pathogenesis. Further studies are crucial to validate biomarkers for accurate diagnosis, paving the way for targeted therapies and improved management of these neurological disorders.
Identifying Key Factors for Recurrence of Genetic Disorder: Insights from Indian Families with Multiple Affected Children
Authors: Menon Kriti , Agarwal Vani
Published: October 2024

This study investigates the factors contributing to the recurrence of severe genetic conditions in multiple children of the same couple, focusing on a cohort of 26 families who had more than one child affected by the same genetic disorder. Conducted at a genetic clinic in India, the study employed a qualitative methodology guided by COREQ guidelines, using semi-structured interviews to explore the interplay of individual beliefs, healthcare provider practices, and systemic healthcare inefficiencies. The interviews were transcribed and analyzed using a combination of content analysis and grounded theory, which allowed for the identification of recurrent themes and emerging ideas. The study found that strong religious and cultural beliefs often led families to disregard medical advice, contributing to the recurrence of genetic conditions. Additionally, significant gaps in healthcare provider knowledge and inadequate reproductive counseling were identified as critical barriers to timely diagnosis and prevention of recurrence. Another major theme was the inherent complexities of genetic diseases and genetic testing, where variable expression of conditions, delayed symptom onset, and limitations of genetic tests themselves often prevented early diagnosis and intervention. This research highlights the need for improved genetic literacy among healthcare providers, culturally sensitive counseling, and better integration of genetic services into the broader healthcare system. By addressing these barriers, the risk of recurrence can be significantly reduced, improving patient outcomes and family well-being. This study is one of the few in India to analyze such factors and underscore the critical need for targeted interventions at multiple levels.
The prevalence of myopia and eye-related behavior among 3 to 18 years: a cross-sectional survey study
Authors: Tian Lu , Zhu Mengxia , Song Yuhan , Wang Yin , Jiang Yan
Published: October 2024

Aims
To determine the current status of myopia and the relationship between eye-related behaviors and myopia in children and adolescents aged 3 to 18 years.
Methods
A total of 3240 children and adolescents from 15 schools were selected for the survey between January and June 2024 in Hubei Province, China. A stratified random cluster sampling method was employed for the collection of samples. All participants were requested to complete the Eye-Related Behavior Assessment Scale for Kindergarten and Primary School Students in Grades 1-3-Parent Version (ERBAS-P) and the Eye-Related Behavior Assessment Scale for Primary School Students in Grades 4–6 and Middle School Students-Student Version (ERBAS-S) on line. Data on socio-demographic factors (gender, grades, region) and myopia rate were collected.
Results
The overall prevalence of myopia among children and adolescents aged 3–18 years in Hubei Province was 34.35%. Risk of myopia was higher in females than in males (OR = 1.27, P = 0.007), in rural than in urban areas (OR = 1.88, P < 0.001), and in children with myopic parents than with non-myopic parents (OR = 3.21, P < 0.001). Furthermore, of the 3240 participants, only 18.1% (n = 587) had good eye-related behavior levels, 46.1% (n = 1494) had moderate eye-related behavior levels, and the rest had poor levels, and there was a significantly higher risk of myopia for poor compared to good eye-related behavior levels (OR = 1.74, P < 0.001). The regression analysis showed that the level of eye-related behavior varied significantly with many of the demographic variables particularly with grades group, gender and whether myopia.
Conclusion
The prevalence of myopia is at a high level among individuals between the ages of 3 and 18 in Hubei province, China, with notable differences between urban and rural populations. The level of eye-related behavior among children and adolescents is suboptimal. A particular focus on fostering the development of positive eye-use habits among younger children should be reinforced in the future.
Corneal Endothelial Damage Following FS-LASIK Combined with Corneal Cross-Linking Surgery: Case Report With Literature Review
Authors: Wang Li , Zhang Xiaofeng
Published: October 2024

Purpose: To report a case of early corneal endothelial damage in a patient with high myopia after undergoing FS-LASIK combined with corneal cross-linking.
Case Description: An observational case report of an 18-year-old male patient with high myopia who underwent FS-LASIK combined with corneal cross-linking. On the third day postoperatively, slit lamp examination revealed corneal edema in the right eye, small pit-like lesions on the endothelial surface of both eyes, and a significant drop in endothelial cell count and percentage of hexagonal cells compared to preoperative levels. One week postoperatively, corneal edema in the right eye and small pits on the endothelial surface of both eyes disappeared, and the number and area of dark spots significantly reduced. At two months postoperatively, the visual acuity of both eyes was 20/20, and the dark spots on the endothelial surface disappeared, the corneal endothelial cell count, the percentage of hexagonal cells, and the coefficient of variation in cell size returned to preoperative levels.
Conclusion: We report a case of early, reversible endothelial damage following FS-LASIK combined with corneal cross-linking.
The role of information processing as an underlying mechanism in the experience of anxiety reactivity and anxiety perseveration; two dissociable dimension of trait anxiety.
Authors: Moore Sophia , Dondzilo Laura , Mazidi Mahdi , MacLeod Colin , Notebaert Lies
Published: October 2024

Purpose.
While long considered a unitary dimension, research has moved towards a multidimensional understanding of trait anxiety. Most relevant to this study, is the conceptualisation of two dissociable dimensions of trait anxiety; anxiety reactivity and anxiety perseveration. Despite the consolidation of this understanding over the past decade, the mechanisms underlying these two dimensions are not well established. The present study examined the novel role of information processing in the experience of anxiety reactivity and perseveration, specifically, how enhanced processing of situational information influences reactivity, and how enhanced processing of implicational information influences perseveration.
Method.
Undergraduate university students (N = 142) completed an experimental session, where they encountered an interview-based stressor. As participants approached this stressor, they were provided with information reflecting one of the two content categories, intended to encourage a situational or implicational processing mode. To facilitate measurement of anxiety reactivity and anxiety perseveration, state anxiety was assessed at crucial junctures across the experimental session.
Results.
Our findings did not provide evidence for the role of enhanced processing of situational information in the experience of anxiety reactivity, nor the role of enhanced processing of implicational information in the experience of anxiety perseveration. An experimental manipulation involving valence revealed that receiving positive information reduced the intensity of state anxiety elevations, in the aftermath of the information processing task.
Conclusions.
Findings are discussed with reference to limitations and future extensions that could investigate the potential role of cognitive biases in this proposed relationship between enhanced information processing and anxiety reactivity and perseveration.
The association between neutrophil percentage and albumin ratio and early deterioration of neurological function after thrombolysis in acute ischemic stroke patients
Authors: Song Hui , Song Guijun
Published: October 2024

Aim
To investigate the correlation between neutrophil percentage to albumin ratio (NAPR) and early deterioration of neurological function after intravenous thrombolysis in acute ischemic stroke patients.
Methods
A retrospective analysis was conducted on 322 acute ischemic stroke patients who received intravenous thrombolysis at the Second Affiliated Hospital of Dalian Medical University from January 2021 to May 2024. 39 patients who experienced early neurological function deterioration (END) after ateplase thrombolysis, while the control group consisted of 283 patients whose symptoms improved after intravenous thrombolysis,we called early neurological improvement(ENI).Collect baseline data and blood parameters for statistical analysis.
Results
Compared with the control group, patients with higher initial NIHSS scores and NPAR had a higher incidence of early END after using thrombolysis (p = 0.041; P < 0.001).
Conclusion
NPAR is associated with early neurological deterioration after intravenous thrombolysis in acute ischemic stroke. Patients with higher NPAR are more prone to occur early neurological deterioration. NPAR is a cost-effective and useful biomarker for predicting early neurological deterioration in patients with acute ischemic stroke after intravenous thrombolysis.
Effectiveness of Educational Intervention for Improving Monkeypox Viral Infection Knowledge in MSM Population
Authors: Wu Xueer , Xu Yuanyuan , Li Xin , Ding Songning , Hu Yang , Zhu Zhengping
Published: October 2024

Background
Monkeypox is a zoonotic disease caused by the monkeypox virus, which has recently exhibited human-to-human transmission globally. Due to its hidden nature and high-risk behaviors, men who have sex with men (MSM) has become a focal point for monkeypox prevention and control. This study evaluates the impact of health interventions on monkeypox knowledge awareness among MSM.
Methods
Through pre- and post-MIP surveys, we analyzed the awareness of monkeypox knowledge, preferences for acquiring monkeypox information, and preferred channels among MSM. Data collection occurred from August 2023 to March 2024, with a total of 1,514 valid questionnaires collected. The Mpox Intervention Program (MIP) included the development and distribution of educational materials, Voluntary Counseling and testing (VCT) clinic consultations, and surveys.
Results
Post-intervention, the total score for monkeypox knowledge awareness significantly increased from 58.50 to 68.47 (P < 0.001), and the knowledge awareness rate rose from 48.66–64.60% (P < 0.001). The intervention significantly improved participants' understanding of monkeypox incubation period, asymptomatic infections, transmission routes, and prevention measures (P < 0.001). MSM preferred obtaining monkeypox knowledge through new media and internet social platforms, with no significant changes in preferences pre- and post-MIP.
Conclusion
The MIP effectively improved monkeypox knowledge awareness and cognitive levels among MSM. These findings provide scientific evidence for optimizing health education strategies and controlling the spread of monkeypox.
Identification and Diagnostic Significance of MPO, PRTN3, and CTNND1 as Biomarkers in Acute Hematogenous Osteomyelitis in Children: A Comprehensive Analysis Using Machine Learning Algorithms
Authors: Yang Jia , Zhang Tianjiu , Chen Kezhi , Luo Jihang , Yu Song
Published: October 2024

Background
Acute hematogenous osteomyelitis (AHO) is a severe bacterial bone infection predominantly affecting children. Early diagnosis is crucial to prevent the progression to chronic osteomyelitis. However, current diagnostic methods are limited in sensitivity and specificity, underscoring the need for reliable biomarkers.
Methods
This study utilized gene expression data from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) associated with AHO. We employed three machine learning algorithms—The Least Absolute Shrinkage and Selection Operator (LASSO) regression, Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and Random Forest (RF)—to screen for potential diagnostic markers. The expression levels of key genes were validated using clinical samples from pediatric AHO patients. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of these biomarkers.
Results
Our analysis identified five candidate genes, among which Myeloperoxidase (MPO), Serum proteinase 3 (PRTN3), Catenin delta 1 (CTNND1) were significantly associated with AHO, MPO and PRTN3 were upregulated, while CTNND1 was downregulated in AHO samples compared to healthy controls. ROC curve analysis demonstrated that CTNND1 (AUC = 0.8832), MPO (AUC = 0.9803) and PRTN3 (AUC = 0.9767) exhibited strong diagnostic potential. Importantly, the expression levels of MPO and PRTN3 positively correlated with disease severity as classified by the Cierny-Mader staging system, whereas CTNND1 expression showed a negative correlation.
Conclusion
MPO, PRTN3, and CTNND1 are promising biomarkers for the diagnosis and monitoring of AHO in children. Their expression levels correlate with disease severity, making them valuable tools for assessing the progression and treatment efficacy in pediatric AHO. Further research is warranted to explore their potential in clinical applications.