bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of key regulatory factors for m6A in myasthenia gravis and characteristics of the immune characteristics
Authors: Wu Yaoqi , Cai Xiaoqing , Jiao Yingying , Zhao Lina , Jiang Qilong , Chen Tongkai , Yang Peidan , Huang Tingjuan , Yang Jie , Song Yafang
Published: November 2024

Myasthenia gravis (MG), a rare autoimmune disorder, presents a complex pathogenesis involving various immune molecules. The modification of N6-methyladenosine (m6A) regulates diverse immune metabolic and immunopathological processes; however, its role in MG remains unclear. We downloaded dataset GSE85452 from the GEO database to identify differentially expressed genes regulated by m6A. The Random Forest (RF) method was utilized to identify pivotal regulatory genes associated with m6A modification. Subsequently, a prognostic model was crafted and confirmed using this gene set. Patients with MG were stratified according to the expression levels of these key regulatory genes. Additionally, MG-specific immune signatures were delineated by examining immune cell infiltration patterns and their correlations. Further functional annotation, protein-protein interaction mapping, and molecular docking analyses were performed on these immune biomarkers, leading to the discovery of three genes that exhibited significant differential expression within the dataset: RBM15, CBLL1, and YTHDF1.The random forest algorithm confirmed these as key regulatory genes of m6A in MG, validated by constructing a clinical prediction model. Based on key regulatory gene expression, we divided MG patients into two groups, revealing two distinct m6A modification patterns with varying immune cell abundances. We also discovered 61 genes associated with the m6A phenotype and conducted an in-depth exploration of their biological roles. RBM15, CBLL1, and YTHDF1 were found positively correlated with CD56dim natural killer cells, natural killer T cells, and type 1 helper T cells. These genes were stable diagnostic m6A-related markers in both discovery and validation cohorts. Our findings suggest RBM15, CBLL1, and YTHDF1 as immune markers for MG. Further analysis of these genes may elucidate their roles in the immune microenvironment of MG.
Association between glycolipid metabolism disorder and coronary microvascular disease: inflammatory indices mediated a partial mesomeric effect model
Authors: Wen Wei , Chi Yi , Liu Mingwang , Gao Mengjie , Xie Beili , Yan Yuxin , Jin Zhidie , Jiang Lulian , Zhang Yiqing , Chen Keji , Zhao Fuhai
Published: November 2024

Background
Coronary microvascular disease (CMVD) is associated with abnormalities in glucose-lipid metabolism. And the triglyceride to high density lipoprotein (HDL) (TG/HDL) ratio can be used to characterize levels of glycolipid metabolism. Therefore, it is hypothesized that increased TG/HDL may trigger CMVD.
Methods
This study enrolled patients with angina pectoris but negative coronary angiograms to explore inflammatory factor-mediated disorder of glycolipid metabolism triggers CMVD. Logistics regression model and subgroup analysis were constructed to explore the associations between TG/HDL and CMVD. Restricted cubic splines were applied to further the associations of TG/HDL with CMVD. Given inflammatory factors as intermediary factor, we investigate the mediating effects of TG/HDL on CMVD.
Results
242 patients were eventually recruited and 150 patients were diagnosed with CMVD. In the multivariable-adjusted model, TG/HDL and inflammatory indexes including the C-reaction protein (CRP), C-reaction protein to lymphocyte ratio (CLR) and inflammatory burden index (IBI) were positively related to CMVD (Odds Ratio (OR) = 1.71, 95% CI = 0.69–4.25; OR = 1.89, 95% CI = 1.32–2.68; OR = 2.76, 95% CI = 1.56–4.89; OR = 1.22, 95% CI = 1.08–1.37, respectively). Mediation analysis indicated that CRP, CLR and IBI mediated 26.37%, 16.89% and 10.45% of the association of TG/HDL with CMVD.
Conclusion
TG/HDL is positively associated with CMVD. And this association appeared to be partially mediated through inflammatory indices.
Enhancing support for patients with Low Anterior Resection Syndrome: Insights and Educational Resources from the LARSCAT Project
Authors: Ribas Yolanda , Muñoz-Duyos Arantxa , Franquet Marta , Guerreiro Isabel , Perau Jordi , Porras Oscar , Rodríguez Dolores , Rojo Jorge , Ramírez Lucia , Rubio Mercè , Marinello Franco , Jiménez-Toscano Marta , Romero Clara
Published: November 2024

Purpose: To address the educational gaps and support needs of patients with Low Anterior Resection Syndrome (LARS) following rectal cancer surgery. The LARSCAT project aimed to develop comprehensive resources to better inform patients and enhance their quality of life.
Methods:
A qualitative study was conducted between November 2022 and March 2023. Seven focus groups were formed, including six patients, two surgeons, and three nurses. Patients had undergone rectal cancer surgery with stoma reversal 2 to 12 years earlier, and all experienced major LARS. The focus groups, held in-person and online, explored the impact on daily life, social and sexual health, mood, rest, and relationships. Thematic analysis was performed to identify key issues and support strategies following the COREQ guidelines.
Results:
Participants reported insufficient information regarding potential dysfunctions after rectal cancer surgery, and difficulties finding reliable information online. The timing of receiving information varied according to individual coping mechanisms. LARS symptoms significantly impacted daily life, social activities, sexual health, and mood. Patients emphasised the need for more tailored information and supplementary written materials to read at their own pace. Consequently, three comprehensive documents were created and made available online.
Conclusion:
This study highlights a significant gap in patient education on the long-term effects of rectal cancer surgery. The resources developed by the LARSCAT project aim to provide essential support to patients and healthcare professionals. Future research should focus on integrating these resources into routine care and evaluating their impact on patient outcomes and quality of life.
Construction and Validation of a Seven-Gene Signature for Predicting Prognosis and treatment response of Melanoma Based on Parkinson's Disease Family Genes
Authors: He Zhiqiang , Zhang Weinan , Li Yanqi , Zhao Xiang , Xie Jinqing , Xie Luoyingzi , Zheng Hong
Published: November 2024

Parkinson's disease (PD) patients generally have a lower cancer risk, except for an increased melanoma risk, suggesting a link between PD genes and melanoma development.However, comprehensive research on the expression and function of the Parkinson's gene family in melanoma is currently lacking. Here, this study aimed to explore the expression of Parkinson's genes in melanoma and their predictive value for prognosis and treatment response will aid in the development of new diagnostic and therapeutic markers for melanoma. Using LASSO regression analysis, we obtained a seven Parkinson's genes signature melanoma prognosis model, including LRRK2, UCHL1, SNCA, VPS13C, SPR, EIF4G1, and FBXO7. Subsequently, internal verification with TCGA cohort and external verification with GEO cohort showed that the seven-gene prognostic model could effectively predict the prognosis for patients with melanoma. Paitents with high risk score had worse overall survival than those with high risk score. The signaling pathways related to anti-tumor immunity, such as interferon α/γ, were significantly activated in the low-risk group. Cancer-related signaling pathways are mainly enriched in high-risk group, such as mTOR, WNT/β-catenin, and Notch pathways. Moreover, low-risk melanoma patients have a higher infiltration of CD8+ T, cytotoxic, and Th1 cells within the tissue as compared with high-risk patients. Melanom patients in the low-risk group had a higher response rate and longer survival after PD-1 treatment, and were more sensitive to drug treatment, such as Nilotinib. We have successfully constructed a 7-gene signature based on Parkinson's disease familial genes, which can efficiently predict the prognosis of melanoma and treatment response.
Ursodeoxycholic acid reduces ACE-2 activity in COVID-19 patients and Calu- 3 cells
Authors: Tong Zhaowei , Zhong Jianfeng , Wang Qi , Qian Fuchu , Zhao Lili , Wang Weihong , Qin Kefeng
Published: November 2024

Background
Reportedly, ursodeoxycholic acid (UDCA) decreases Angiotensin-converting enzyme 2 (ACE2) activities by inhibiting FXR to prevent SARS-CoV-2 infection.
Methods
Covid-19 patients (n=142, male=72, female=70) from January to May 2023 were divided into UDCA-free (n=53) and UDCA (n=89) groups and treated withnirmatasvir/ritonavir or molnupiravir for 5 days. Patients in the UDCA group were additionally given UDCA for 10 days. ACE2 was detected and clinical outcomes were assessed. Calu-3 cells were infected with the Covid-19 Spike (XBB.1.5) pseudovirusand incubated with or without UDCA.
Results
On day 0 (before treatment), 3, 6, 9 (after anti-viral drug and/or UDCA treatment), ACE2 in serum and plasma in UDCA-free group was ~41 ng/ml (p=0.9962), and ~68ng/ml (p=0.6179); in UDCA group from 40.1±9.6 to 20.8±5.8 ng/ml (p=0.0000), and 68.8±15.6 to 30.2±7.7 ng/ml ( p=0.0000). In UDCA group, ACE2 mRNA in blood cells was from ~100% to 58.5±13.2% (p=0.000) on day 6 and time for fever return to normal shorter (p=0.0001). In Calu-3 cells, UDCA reduced ACE2 protein and mRNA, and blocked Covid-19 pseudovirus infection.
Conclusion
UDCA reduces ACE2 activity in Covid-19 patients and Calu-3 cells, blocks Covid-19 pseudovirus infection in Calu-3 cells and improves the clinical outcomes. UDCA may be a potential drug for prevention and treatment of SARS-CoV-2 infection.
Outcomes following second allogeneic stem cell transplant for graft failure or poor graft function: a single centre experience
Authors: Kim Jowon L. , Joe Moss A. Bruton , Chung Shanee , Cherniawsky Hannah , Forrest Donna L , Kuchenbauer Florian , Lad Deepesh , Nantel Stephen H , Narayanan Sujaatha , Nevill Thomas J , Judith Rodrigo , Sanford David , Song Kevin W , Stubbins Ryan J , Toze Cynthia L , White Jennifer , Mourad Yasser Abou , Roy Claudie
Published: November 2024

Graft failure is a rare but life-threatening complication following allogeneic hematopoietic stem cell transplantation (HSCT). We aim to review the outcomes of patients who underwent a second allogeneic HSCT (HSCT2) for graft failure or poor graft function following a previous allogeneic HSCT (HSCT1) at our centre. This restrospectve study included adult patients receiving HSCT2 for graft failure or poor graft function between February 2001 and July 2021. Survival functions were estimated using the Kaplan-Meier method.
Twenty-one patients were identified, 11 with primary and 10 with secondary graft failure. In the 14 patients for whom chimerism data was available, 10 had loss of donor chimerism, 2 had mixed chimerism, and 2 had full donor chimerism. The median time between HSCT1 and HSCT2 was 55 days (range 38-168 days) and 278 days (range 75-3074 days) for PGF and SGF, respectively. For HSCT2, matched unrelated donor was the most common donor type (33%) and the same donor as HSCT1 was used in 24%. Most patient received peripheral blood stem cell source (81%) and reduced intensity conditioning (100%) for HSCT2. Graft-versus-host-disease (GVHD) prophylaxis was calcineurin inhibitor-based with either methotrexate or mucophenolate mofetil.
The median follow-up for survivors was 120 months (range 7-170). Overall survival was 52% at 2 years, and 46% at 5 years. Death before day+30 occurred in 5 patients (24%). Non-relapse mortality (NRM) was the major cause of treatment failure, with 2-year NRM of 48%. Infectious complications was the most common cause of death. Relapse occurred in 3 patients (14%). All patients who lived beyond day+30 successfully engrafted, with a median time to neutrophil recovery of 22 days (range 11-31). The incidence of acute GVHD was 50% in the 16 patients who survived beyond day+30, and chronic GVHD was 50% in the 14 patients who survived beyond day+100. Two patients subsequently developed SGF and both underwent a third allotransplant.
Our real-world data confirms that a second allogeneic HSCT for graft failure or poor graft function is associated with high NRM and early mortality. Nonetheless, there are long-term survivors and further studies should focus on reducing NRM in these patients.
The Association between METS-IR Index and Obstructive Sleep Apnea-Hypopnea Syndrome: A Cross-Sectional Study Based on the National Health and Nutrition Examination Survey from 2015 to 2018
Authors: Hou Yisen , Li Rui , Xu Zhen , Chen Wenhao , Li Zhiwen , Jiang Weirong , Meng Yong , Han Jianli
Published: November 2024

Background
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep disorder closely associated with metabolic syndrome. The metabolic score for insulin resistance (METS-IR) is a new indicator used to assess insulin resistance. However, evidence on the association between METS-IR and OSAHS remains limited.
Objective
This study aimed to analyze the association between METS-IR and OSAHS in American adults.
Methods
This study utilized cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2015 and 2018. We analyzed METS-IR and the prevalence of OSAHS in adult participants. Individuals aged 20 years and older were included, while those without available BMI, fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) data were excluded. Logistic regression analysis, subgroup analysis, and restricted cubic spline analysis were employed to evaluate the association between METS-IR and OSAHS, adjusting for potential confounders including sex, age, race/ethnicity, education level, income, smoking status, alcohol consumption, diabetes status, and lipid levels.
Results:
A total of 4274 adult participants were included in the study. Participants were categorized into quartiles based on METS-IR levels, with ranges of 19.98–33.94, 33.94–41.60, 41.60-51.15, and 51.15-124.47, respectively. After adjusting for age, sex, race/ethnicity, education level, smoking status, alcohol consumption status, hypertension status, diabetes status, and dyslipidemia status, METS-IR was positively associated with the risk of OSAHS (OR = 1.05, 95% CI: 1.03, 1.07). Specifically, each one-unit increase in METS-IR was associated with a 5% increase in the risk of OSAHS. Subgroup analysis revealed a significant positive correlation between METS-IR and the incidence of OSAHS in the highest METS-IR quartile. This association was particularly pronounced among Mexican Americans (OR = 6.33, 95% CI: 2.13, 23.67) and non-Hispanic Black individuals (OR = 12.22, 95% CI: 5.89, 26.62). Additionally, after controlling for potential confounders, the association between METS-IR and OSAHS remained significant. Notably, individuals with diabetes, hypertension, and hypertriglyceridemia were at a greater risk of OSAHS.
Conclusion:
The results of this study demonstrated a significant positive association between METS-IR and the incidence of OSAHS, which persisted after adjusting for various confounders. This suggests that METS-IR may be a potential risk factor for OSAHS. In clinical practice, the management of metabolic syndrome should be emphasized to prevent the occurrence of OSAHS.
Evaluation of two low-level laser techniques as an adjunct to basic periodontal therapy: a randomized clinical trial
Authors: Silva Régia Carla Medeiros da , Silva Lucas Gabriel Cunha da , Cruz Natália Teixeira Silva , Barbosa Adylla Rominne Lima , Maia Paulo Raphael Leite , Martins Ana Rafaela Luz de Aquino
Published: November 2024

Aim: To assess and compare two techniques of low-level laser application—transgingival (TLLLT) and intrasulcular (ILLLT)—used in photobiomodulation as an adjunct to basic periodontal therapy (BPT) in patients with periodontitis.
Methods: A randomized, split-mouth, double-blind clinical trial was conducted, selecting three diseased periodontal sites from different quadrants in each patient. These sites were assigned to one of three treatment groups: SRP (control), SRP + TLLLT (test 1), and SRP + ILLLT (test 2). Low-level laser therapy in the test groups was applied at 48 hours, 7 days, and 14 days after full-mouth SRP. Clinical parameters such as probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were assessed at baseline (T0), 3 months (T1), and 6 months (T2). Standardized periapical radiographs were used to assess radiographic bone density (RBD) 6 months post-treatment. Statistical analyses included repeated measures ANOVA for continuous variables and chi-square tests for categorical variables, with significance set at p < 0.05 and a 95% confidence interval.
Results: Significant reductions in PD (p < 0.001) and CAL (p < 0.001) were observed across all groups at 3 and 6 months, with no significant differences between groups. There were also no significant changes in BOP and RBD between groups at the follow-up intervals.
Conclusion: Adjunctive photobiomodulation did not provide additional clinical or radiographic benefits over SRP alone, regardless of the laser application technique employed.
NET-related genes predict prognosis and are correlated with the immune microenvironment in osteosarcoma
Authors: Chu Dawei , Huang Rui , Shi Jian dang , Xu Ruiqing , Wei Daihao
Published: November 2024

Background
Osteosarcoma is the most common primary bone tumor. It has a high rate of early metastasis, and its treatment is one of the most challenging topics in the bone tumor field. Recent studies have shown that neutrophil extracellular traps play an important role in tumor metastasis and may provide new horizons for exploring metastasis in osteosarcoma.
Methods
OS data were downloaded from the TARGET database and Gene Expression Omnibus datasets. Univariate Cox regression was conducted to assess NETRGs. Patients were subsequently categorized into high- and low-risk groups on the basis of risk score values derived from multivariate Cox analysis, and prognostic models were established. The immune infiltration of relevant genes and drug sensitivity of key genes were also analyzed.
Results
A total of 15 NET-related genes associated with osteosarcoma metastases were identified. Among them, a total of 4 genes were related to prognosis, namely, MAPK1, CFH, ATG7 and DDIT4, and a prognostic model based on these 4 genes was established. The prognosis was worse in the high-risk group, whose areas under the ROC curves (AUCs) were 0.857, 0.779, and 0.689 at 1, 3, and 5 years, respectively. The key genes were subsequently found to be associated with the infiltration of 20 types of immune cells. Finally, the small-molecule drug toxin c 10, an approximately 6700 mw protein, may target key genes. Finally, ATG7 was validated at the histological level by combining the results of the validation group dataset analysis.
Conclusions
A risk model based on 4 NETRDEGs is a reliable prognostic predictor for OS patients, and ATG7 may serve as a new diagnostic and therapeutic target.
Effects of Different Physical Activity Interventions on Symptoms of Anxiety and Depression in Children and Adolescents ：A Network Meta-Analysis of Randomized Controlled Trials
Authors: Zhang Zhaoxu , Li Lan , Dong Kuan , Li Dong , Guo Ke-Lei
Published: November 2024

Background: Anxiety and depression are widespread mental health conditions worldwide, with significant negative impacts on patients. These conditions are especially prevalent among adolescents. Recently, exercise therapy has gained popularity as a supplementary approach to managing anxiety and depression. Numerous studies have started investigating the relationship between physical activity and anxiety and depressive symptoms in adolescents. Nonetheless, systematic evidence to guide the optimal choice of physical activities remains insufficient. This study aims to compare and rank various physical activity interventions to determine the most effective ones for treating adolescent anxiety and depression, ultimately providing valuable insights for clinical practice.
Methods: A thorough search was performed in PubMed, Embase, Web of Science, and the Cochrane Library to identify randomized controlled trials evaluating the impact of physical activity interventions on children with anxiety and depression. The search encompassed all available records from the inception of each database up to April 2024. Literature screening, data extraction, and quality evaluation were managed independently by two reviewers. Subsequently, Stata version 15.1 was employed to conduct a network meta-analysis.
Results: A total of 25 studies were included in the analysis. The findings demonstrate that High-intensity interval training is the most effective intervention for preventing and reducing depression and anxiety in children(SUCRA = 85.4%), followed by REC (SUCRA = 82.2%). Additionally, Mind-body exercise and Moderate-to-vigorous exercise were identified as relatively effective strategies, with SUCRA scores of 70.9% and 67.1%, respectively.
Conclusions: Our study shows that High-intensity interval training and Resistance training are the most effective interventions overall. Selecting the optimal exercise type should be individualized based on each child’s unique needs while encouraging consistent participation in physical activity.
PROSPERO: CRD42024563543 DATE: July 10, 2024 retrospectively registered
Prevalence, incidence and impact of cancer in atrial fibrillation: a systematic review and meta-analysis of 6,600,000 patients
Authors: Mao Shaobin , Wang Leigang , Fan Hongxuan , Yang Ling , Yang Zhuoxuan , Zhang Wenjing , Wang Miao , Hao Liuyi , Liang Bin
Published: November 2024

Aims
Contemporary studies have indicated that atrial fibrillation (AF) is common among cancer patients, and affects the prognosis of cancer patients. The other hand, AF and cancer share the same risk factors, while the prevalence, incidence and impact of cancer in AF patients is unclear. Our aim was to estimate the prevalence and incidence of cancer, and focus on the impact of cancer on clinical outcome.
Methods and Results
We searched the PubMed, Web of science, Embase and Cochrane Library databases, and conducted according to international guidelines to perform a system review and meta-analysis. All studies reporting the prevalence and incidence of cancer were included. We extracted the data from these studies and used the random effect model to pool the result. The prevalence and incidence of cancer overall were 1153.31 (95%CI: 959.19-1380.72) per 10000 patients, 173.28 (95%CI: 131.89-227.66) per 10000 person-years, respectively. Otherwise, cancer prevalence and incidence had been shown to vary by cancer type, the incidence also varies gender and comorbidities. And cancer is associated with higher risk of all-death (OR: 1.78, 95%CI: 1.51–2.08) and bleeding (OR: 1.44, 95%CI: 1.26–1.65), no significant differences in cardiovascular death and stroke/system embolism.
Conclusions
Cancer is common in AF patients, affecting 11% of patients. The incidence of cancer cannot be ignored. Cancer is associated with the worse outcome in AF patients, with more than 1.7-flod higher risk of all-death and increased the risk of bleeding.
Use of CRISP modifiers for adults undergoing cardiac catheterization procedures: A single center experience
Authors: Reynolds Kathryn P , Mejia Ernesto , Soszyn Natalie , Morgan Gareth , Zablah Jenny E.
Published: November 2024

Background The Catheterization RISk Score for Pediatrics (CRISP) has been validated and widely adopted as a model to predict adverse outcomes. We sought to determine if the addition of three modifiers (NYHA Class > 2, prior sternotomies > 2, and BMI > 30) to the CRISP score would better predict adverse events (AE) in adults undergoing cardiac catheterization at our institution.Methods All adults (> 18 years) who underwent cardiac catheterization at the Children’s Hospital Colorado from November 2016 to November 2021 were included. Baseline and modified CRISP scores with adult modifiers and AEs were analyzed.Results Of a total of 401 cases, there were 27 AEs (6.7%). A higher CRISP score was associated with an increased risk of AEs (p = 0.004). A ROC analysis of the CRISP score gave a AUC of 66% with a cut-off point of 5.5 giving a sensitivity of 74% and specificity of 52%. The modifiers individually did not significantly correlate with AEs. Higher modified CRISP score was similarly associated with an increased risk of AEs (p = 0.01). ROC analysis for the modified CRISP score gave an AUC of 64%. A cut-off point of 6.5 gave the best result with a sensitivity of 59% and specificity of 61%.Conclusion A modified CRISP score which included adult modifiers similarly predicts AEs in adults with congenital heart disease. These adult modifiers are easy to incorporate into the CRISP score. The CRISP score also predicted AEs in adults with congenital heart disease.
Differential prognostic significance of tumor size and lymph node in invasive lobular carcinoma of breast
Authors: Kang Eunhye , Shin Ik Beom , Jung Ji-Jung , Byeon Jinyoung , Choi Yunhee , Cheun Jong-Ho , Lee Han-Byoel , Han Wonshik , Kim Hong-Kyu , Moon Hyeong-Gon
Published: November 2024

Despite invasive lobular carcinoma (ILC) having distinct clinical and pathological characteristics, it shares the same prognostication system and adjuvant treatment strategies with invasive ductal carcinoma (IDC). We analyzed data from 16,410 IDC and ILC patients treated at Seoul National University Hospital (2005–2022), along with 247,290 cases from the Surveillance, Epidemiology, and End Results (SEER) database (2010–2015). ILC patients were characterized by older age at diagnosis, larger tumors, and predominantly HR-positive/HER2-negative status. ILC showed unique prognostic implications, particularly in anatomic features. Unlike IDC, tumor size and nodal status had differential prognostic impact on survival in ILC. While T stages showed no significant survival difference in ILC patients, nodal involvement had a more pronounced prognostic impact in both SNUH and SEER datasets. These findings suggest that in ILC, tumor size may not be as strong a survival predictor as in IDC, while advanced nodal involvement indicates higher breast cancer-specific mortality risk.
Factors Associated with the Pricing and Reimbursement System of Orphan Drugs in South Korea
Authors: Lee Se Hee , Lee Sung Kyung , Bang Joon Seok , Lee Jong Hyuk
Published: November 2024

Background Orphan drug pricing in South Korea, including its workings and determinants, is a complicated aspect of the country’s health care system. Therefore, this study identified the factors associated with the pricing and reimbursement system of orphan drugs in South Korea.Methods The study screened a total of 66 orphan drugs out of the whole set of newly reimbursed drugs from 2012 to 2022. The analyses presented the characteristics of the orphan drugs and accounted for correlations between treatment cost and other seemingly related variables. Formal multivariate regression analyses pointed out associated factors in multivariate settings.Results Annual treatment cost per patient displayed a weakly negative correlation with the number of patients. Meanwhile, treatment cost exhibited a strongly positive correlation with the average of adjusted prices in seven advanced countries, reaching an adjusted R-squared value of 0.99. Treatment cost also showed a positive correlation with budget impact.Conclusions The pricing of orphan drugs in South Korea is predominantly influenced by external reference pricing. Drugs targeting smaller patient populations tend to be priced higher. Thus, the study highlights the interplay between drug pricing and external reference prices, drug characteristics, and pricing and reimbursement pathways. The findings can guide policymakers, pharmaceutical companies, and health care providers in their efforts to balance patient accessibility with orphan drug development and the financial sustainability of public health insurance.
A Comparative Study of X-ray and 3D CT in the Evaluation of Pauwels Classification for Femoral Neck Fractures
Authors: Sun Ming , Liang Hairui , Bai Tong , Zhang Tianyu , Xu Rongda , Duan siyu , Cai Zhencun
Published: November 2024

Background
To compare the accuracy of X-ray and 3D CT in measuring the Pauwels angle of femoral neck fractures and the reliability of these methods in guiding Pauwels classification.
Methods
X-ray and CT images of 40 femoral neck fracture patients from our hospital were collected. Three physicians measured the Pauwels angle on both X-ray and CT images using the PACS Workstation system, performing the measurements twice and classifying the fractures based on the Pauwels classification. Consistency and reproducibility analyses were conducted to evaluate the performance of the two methods.
Results
The Pauwels angles and classification results obtained by the chief physician, attending physician, and resident physician using both X-ray and CT methods showed statistically significant differences, with P values all < 0.05. For the consistency analysis, the interclass correlation coefficients (ICC) for two measurements were: for the X-ray method, ICCs of 0.712, 0.882, and 0.578 for 1vs2, 1vs3, and 2vs3, respectively, and ICCs of 0.357, 0.631, and 0.596 for the same pairs; for the CT method, ICCs of 0.935, 0.966, and 0.960 for 1vs2, 1vs3, and 2vs3, and ICCs of 0.896, 0.952, and 0.872 for the same pairs. The reproducibility analysis for the three physicians showed that the ICCs for the X-ray method were 0.767, 0.720, and 0.754, while for the CT method, the ICCs were 0.945, 0.918, and 0.964. The CT method demonstrated superior consistency and reproducibility compared to the X-ray method.
Conclusions
Compared to X-rays, 3D CT scanning is more accurate in measuring the Pauwels angle of femoral neck fractures and provides more reliable guidance for Pauwels classification, with higher clinical reproducibility. Therefore, it is recommended to use CT scanning instead of X-ray for preoperative evaluation of fracture stability in femoral neck fracture patients.
Comparative analysis of the efficacy and safety of complete da Vinci robot versus laparoscopy in total gastrectomy and delayed detached gastric modified Overlap esophagojejunostomy for gastric cancer: a retrospective cohort study
Authors: Huang Xiaodong , Li Weidong , Han Xiaowen , Zhang Jiayi , Chen Hao
Published: November 2024

Objective：To investigate the feasibility and safety of fluorescence laparoscopic intraoperative positioning combined with complete da Vinci robotic total gastrectomy for gastric cancer and delayed detachment of the stomach in modified Overlap oesophagojejunostomy.
Methods：The clinical data of 22 gastric cancer patients treated with fluorescent laparoscopic intraoperative localization combined with complete da Vinci robotic total gastrectomy or fluorescent laparoscopic total gastrectomy at the Department of Oncology, the Second Hospital of Lanzhou University, were retrospectively analyzed and relevant literature was searched and reviewed.
Results：The clinical data of 22 patients were included for analysis, including 11 in the laparoscopic group and 11 in the robotic group. All surgeries were successfully completed. In terms of baseline data, there was no statistically significant difference between the two groups. Robotic group was higher than laparoscopic group in terms of operative time and hospitalisation costs (P<0.05); the neutrophil ratio on the third postoperative day was lower in the robotic group than in the laparoscopic group (P <0.05); the comparison between the first five cases and the last six cases in the robotic group showed that the intraoperative blood loss in the last six cases was lower than that in the first five cases (P<0.05).
Conclusions：Intraoperative localization with fluorescence laparoscopy combined with total robotic gastrectomy for gastric cancer and modified Overlap esophagojejunostomy with delayed gastric transection has equivalent efficacy to fluorescence laparoscopy total gastrectomy, and is safe and feasible. With the increase of surgical proficiency, intraoperative blood loss can be better controlled, which is worthy of clinical promotion and application.
Comparative analysis of 3D-culture techniques for multicellular colorectal tumour spheroids and development of a novel SW48 3D model
Authors: Mateos-Sánchez Carlos , González Beatriz , de Miguel-García Gisela , Marcote-Corral Iris , Alonso Sergio
Published: November 2024

Background
Colorectal cancer (CRC) remains a significant global health challenge, with nearly 2 million diagnosed cases and over 900,000 deaths annually despite therapeutic advancements. The high morbidity and mortality rates underscore the need for more efficient therapies. Three-dimensional (3D) cell culture models have emerged as more physiologically relevant alternatives to traditional two-dimensional (2D) models for drug screening and mechanistic studies. However, generating consistent spheroids across different CRC cell lines presents technical challenges, and protocols remain inconsistent.
Methods
This study evaluated different 3D culture methodologies, i.e. overlay on agarose, hanging drop, and U-bottom plates without matrix or with methylcellulose, Matrigel or collagen type I hydrogels, across eight CRC cell lines. Tumorsphere morphology and cell viability were analysed. Co-cultures with immortalised colonic fibroblasts were explored to improve the physiological relevance of the tumour models.
Results
The study provided insights into the morphological and viability characteristics of 3D cultures across multiple CRC cell lines. A novel compact spheroid model using the SW48 cell line was successfully developed. Co-culture experiments with fibroblasts offered additional insights into tumour-stroma interactions in a 3D setting.
Conclusions
This study contributes to the advancement of more physiologically relevant in vitro CRC models, potentially enhancing the accuracy of preclinical studies and drug screening processes. The successful 3D model of SW48 expands the repertoire of CRC cell lines available for 3D culture studies. These findings may lead to improved preclinical models for CRC research and drug development.
Cone-Beam Computed Tomography as a Tool in Analyzing Asymmetry of Facial Soft Tissue
Authors: Ferreira Geovane Miranda , Evangelista Karine , Ruellas Antônio Carlos Oliveira , Valladares-Neto José , Bueno Juliano Martins , Cevidanes Lucia Helena Soares , Silva Maria Alves Garcia
Published: November 2024

Objective
This study aimed to evaluate the asymmetry of the facial soft tissue in conjunction with skeletal tissue using cone beam computed tomography (CBCT).
Materials and Methods
CBCT images of 39 individuals were evaluated and divided into symmetric (< 2mm) and asymmetric (> 2mm) groups based on mandibular deviation in relation to the midline sagittal plane. The groups were paired according to the anteroposterior skeletal pattern, sex, and age. The facial soft tissue was delimited and segmented into 8 different parts (left and right sides of the upper lip, lower lip, zygoma, and mandible) using facial landmarks as a reference, followed by reconstruction of its total volume. The mirroring method between the sides of the face was used for bone and soft tissues, followed by registration of images by voxel superimposition to visualize the differences between the sides. Volumetric differences were quantified between the right and left sides using paired comparison tests. The distances between soft and skeletal middle landmarks were established to verify the alignment of the skeletal and soft midsagittal plane. The reliability of mirroring in soft tissues and the method error was assessed by measuring the distance between the Glabella soft (Gl’) and Subnasal (Sn) landmarks of the original and mirrored samples.
Results
The results showed that the landmarks presented an average 3D deviation of 0.86 mm (Gl’), 0.74 mm (Sn), 0.19 mm (Gl’), and 0.45 mm (Sn), respectively. The intra- and inter-examiner values showed agreement above 0.75. Group comparisons revealed misalignment of soft and hard tissue midsagittal planes in 67% of the total sample but no significant differences in bone-soft tissue landmark distances or left-right volumetric differences within either the symmetric or asymmetric group. However, the asymmetric group showed a tendency for greater differences, especially in the lower facial third.
Conclusion
The volumetric assessment of soft tissues using 3D models based on CBCT is a valid and reliable method that can be employed to identify asymmetries and plan surgical and minimally invasive interventions on the face.
Clinical relevance:
The assessment of soft tissues by 3D models can potentially improve diagnosis, planning and outcomes of orthodontic and surgical treatment of facial asymmetries.
Preoperative CT Lymph Node Size as a Predictor of Nodal Metastasis in Resectable Colon Cancer: A Retrospective Study of 694 Patients
Authors: Kawazoe Tetsuro , Nakanishi Ryota , Ando Koji , Zaitsu Yoko , Kudou Kensuke , Nakashima Yuichiro , Oki Eiji , Yoshizumi Tomoharu
Published: November 2024

Purpose
This study aimed to investigate the efficacy of measuring lymph node size on preoperative CT imaging to predict pathological lymph node metastasis in patients with colon cancer to enhance diagnostic accuracy and improve treatment planning by establishing more reliable assessment methods for lymph node metastasis.
Methods
We retrospectively analyzed 1,056 patients who underwent colorectal resection at our institution between January 2004 and March 2020. From this cohort, 694 patients with resectable colon cancer were included in the study. We analyzed the relationship between lymph node size on preoperative CT imaging and lymph node metastasis identified on postoperative pathological examination.
Results
The optimal cutoff values for the maximum long diameter and short diameter of regional lymph nodes on preoperative CT were identified as 6.5 mm and 5.5 mm, respectively, with an AUC of 0.7794 and 0.7755, respectively. Notably, the predictive accuracy varied by tumor location. Higher cutoff values were observed in the right-sided colon (maximum long diameter: 7.7 mm, maximum short diameter: 5.9 mm) compared to the left-sided colon (maximum long diameter: 5.8 mm, maximum short diameter: 5.2 mm).
Conclusion
Lymph node size on preoperative CT is a significant predictor of pathological lymph node metastasis in colon cancer. Notably, the optimal cutoff values for predicting lymph node metastasis vary depending on the specific region within the colon.
Legal Assist AI-Leveraging Transformer based Model for Effective Legal Assistance
Authors: Gupta Jatin , Sharma Akhil , Singhania Saransh , Abidi Ali Imam
Published: November 2024

Pursuit of accessible legal assistance in India faces a critical gap, as many citizens struggle to leverage their legal rights due to limited awareness and access to relevant legal information. This paper introduces Legal Assist AI, a transformer-based model designed to bridge this gap by offering effective legal assistance through large language models (LLMs). The system leverages advanced natural language processing (NLP) techniques to analyze and respond to both subjective and objective legal queries, catering to diverse users such as legal professionals, scholars, and the general public. The model was fine-tuned on extensive datasets from the Indian legal domain, including the Lawyer_GPT_India and All India Bar Examination (AIBE) dataset, providing a robust understanding of the complexities of Indian law. The model was evaluated against state-of-the-art models such as GPT-3.5 Turbo and Mistral 7B, achieving a 60.08% score on the AIBE, outperforming its competitors in legal reasoning and accuracy. Unlike other models, Legal Assist AI avoided common issues such as hallucinations, making it highly reliable for practical legal applications. It showcases the model's applicability in real-world legal scenarios, with future iterations aiming to enhance performance and expanding its dataset to cover a broader range of multilingual, and case-specific queries as well.
The impact of TP53 co-mutation on the clinical outcomes of advanced non-small cell lung cancer patients with EGFR sensitizing mutation: An updated systematic review and meta-analysis of prospective clinical trials and a single-center retrospective cohort study
Authors: Huang Wenshu , Wei Huiting , Jiang Wei , Su Cuiyun , Zhao Yun , He Jianbo , Tan Liping , Chen Shubin , Zhou Shaozhang
Published: November 2024

Purpose
The currently updated research was conducted in order to determine the effect of TP53 co-mutation on the clinical outcomes of patients with advanced non-small cell lung cancer who also had EGFR-sensitizing mutation.
Methods
We used the MINORS Methodological items for non-comparative single-arm clinical research, and for eligible randomized clinical trials (RCTs), we used the Cochrane risk of bias instrument. Outcomes including progression-free survival (PFS) and overall survival (OS) were extracted for further analysis. A total of 164 advanced non-small cell lung cancer (NSCLC) patients were enrolled in the study. The prognostic value of TP53 mutation status for PFS and OS was evaluated using Kaplan-Meier survival analysis and Cox's proportional hazards regression model.
Results
A pooled incidence of TP53 co-mutation was 49.6%. With regard to survival analysis, patients with no TP53 mutation showed a significantly longer PFS (HR = 0.66; 95% CI = 0.57–0.76; P < 0.0001), in the meantime, meta-analysis demonstrated a significantly shorter OS in patients harboring concurrent TP53 mutation treated with EGFRTKIs (HR = 0.61; 95% CI = 0.51–0.74; P < 0.0001). Mutations in exon 4 or 7 of TP53 served as independent worse prognostic factors for disease progression compared with no TP53 co-mutation (HR = 2.49, 95% CI: 1.56–3.97, P < 0.001) and the others TP53 mutation (HR = 2.38, 95% CI: 1.46–3.86, P < 0.001).
Conclusion
Individuals with advanced NSCLC who also had TP53 co-mutation had worse shorter PFS and OS. Particularly, TP53 exon 4 or exon 7 mutations suggest a poorer prognosis.
Sexual dysfunction and quality of life in cervical and endometrial cancer patients before and after low-dose-rate brachytherapy: a cohort study from Northeast Mexico.
Authors: Alcorta Celia B. González , Garza Adelina Alcorta , Sánchez Daneli Ruiz , Martínez Blanca Angélica Soto , Núñez Fernando Alcorta , Reynoso Itzel Lidey Galaviz , Sierra Paola A. López , Guerrero Juan Francisco González , Gutiérrez Oscar Vidal
Published: November 2024

Background and objective. The available research on low-dose-rate (LDR) brachytherapy in gynecology cancer has focused mainly on treatment toxicity. It does not include aspects such as sexual desire, sexual arousal, orgasm, satisfaction, or quality of life. This study assessed sexual function and quality of life before and after LDR brachytherapy in cervical and endometrial cancer patients. We also identified risk factors that contribute to the loss of sexual function and those associated with an improvement in quality of life 3–6 months post-brachytherapy.Methods. We prospectively followed a cohort of patients with a histopathological diagnosis of cervical and endometrial cancer treated with LDR intracavitary brachytherapy between February 2020 and November 2022 (n = 139). We used the SyDSF-AP, FACT-G, PHQ-9, and PHQ-15 scales collected through a self-administered questionnaire before and 3–6 months after treatment. The incidence rates were estimated. Binary and ordinal multiple logistic regression were used to examine risk factors for sexual dysfunction (coded as yes vs. no) and quality of life (coded as worsened, remained poor or fair, improved) after LDR brachytherapy, respectively.Results. The incidence of sexual dysfunction was 14.4%, with 30% of individuals already experiencing sexual dysfunction at baseline. Higher education decreased the likelihood of starting or maintaining sexual dysfunction (adjusted odds ratio 0.10, 95% CI 0.01, 0.97). Physical well-being improved after treatment (69.3 ± 24.1 vs 78.7 ± 20.2, p < 0.001; effect size = 0.34). Age, major depression, and sexual dysfunction reduced the likelihood of starting or maintaining a good quality of life.Conclusions. More than 1 in 10 patients developed sexual dysfunction and physical well-being was the only area that improved after treatment. Schooling was associated with sexual dysfunction. In contrast, age, depression, and sexual dysfunction negatively impact quality of life. Research in this area helps increase awareness and understanding of how healthcare providers can better support sexual and health-related well-being.
Osteonecrosis modulates extracellular matrix deposition through collagen I deposition in obese rats via the TGF-β protein
Authors: Lima Wilson José de Miranda , Pontes Jannerson Cesar Xavier , Araújo Rubens Silva , Sousa Maria Carolina Paiva , Pessoa Wallace Felipe Blohem , Alves Adriano Francisco
Published: November 2024

Osteonecrosis, characterized by the death of bone tissue in the jaws, is termed bisphosphonate-related osteonecrosis of the jaws (BRONJ) when caused by bisphosphonate use. Obesity, a significant public health issue, has been associated with both BRONJ and other oral conditions, such as caries and periodontitis, highlighting the relationship between systemic factors and oral health. This study investigated the influence of TGF-ß, TNF-α, and collagen I on bone tissue and their correlation with mandibular osteonecrosis in obese rats. Twenty-four male Wistar rats (Rattus norvegicus) were divided into four groups: healthy, osteonecrotic, obese, and obese with osteonecrosis. Osteonecrosis was induced with zoledronic acid (250 µg/kg), which was administered weekly for eight weeks, combined with tooth extraction, while obesity was induced by a high-glycemic diet. The analyses revealed that, compared with the patients in the osteonecrosis group, the obese group with osteonecrosis had a 67.99% increase in the necrotic area, whereas the obese group had a 43.85% reduction. The healthy group had the largest reduction (97.11%). For TNF-α, there was intense staining in the osteonecrosis (27.59 ± 7.65 µm²) and obese (25.52 ± 8.31 µm²) groups, whereas the level of TGF-β was greater in the obese with osteonecrosis group (44.98 ± 3.93 µm²). Collagen I staining was more intense in healthy animals. The potential interaction between TGF-ß, TNF-α, and collagen I in bone tissue may be essential for understanding bone remodeling; however, further studies are needed to explore these mechanisms.
Characteristics Analysis of Multifocal Electroretinogram in Non-proliferative Diabetic Retinopathy
Authors: Li Ziwei , Cui Yan
Published: November 2024

Purpose
To investigate multifocal electroretinogram (mfERG) changes in non-proliferative diabetic retinopathy (NPDR) patients compared to normal people, and to clarify the differences in changes across various regions of the retina.
Methods
We selected 18 healthy individuals (22 eyes) and 26 NPDR patients (45 eyes), using the RETscan device for mfERG examination. We analyzed mfERG results for amplitude density and latency of P1 and N1 waves in five rings and four quadrants centered on the fovea.
Results
In the normal group, mfERG amplitude density decreased from the fovea outward, with significant differences between rings (P < 0.05). The NPDR group showed reduced amplitude density and longer latencies compared to the normal group, particularly in rings 1–2 for P1 wave amplitude density and in all rings for N1 and P1 wave latencies (P < 0.05). In quadrant analysis, the NPDR group had greater P1 amplitude density in the superonasal quadrant and shorter N1 latency in the superotemporal quadrant compared to other areas (P < 0.05). However, in normal individuals, we did not find any differences in retinal function among 4 quadrants.
Conclusions
Both normal and NPDR individuals show a decline in retinal nerve function from the foveal center to the periphery. Retinal function in normals is affected by age, but not in NPDR patients, which only correlates with BCVA. NPDR patients exhibit early and severe damage to nerve cells near the fovea, with the inferotemporal retina being more susceptible than other regions.