bluuebunny/crossref_metadata_2025 huggingface dataset:
COL5A2 is a prognostic-related biomarker and correlated with immune infiltrates in gastric cancer based on transcriptomics and single-cell RNA sequencing
Authors: Chen Meiru , Zhu Xinying , Zhang Lixian , Zhao Dongqiang
Published: September 2023

Background

There is still a therapeutic challenge in treating gastric cancer (GC) due to its high incidence and poor prognosis. Collagen type V alpha 2 (COL5A2) is increased in various cancers, yet it remains unclear how it contributes to the prognosis and immunity of GC.

Methods

The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to download transcriptome profiling (TCGA-STAD; GSE84437), single-cell RNA sequencing (scRNA-seq) data (GSE167297) and clinical information. COL5A2 expression and its relationship with clinicopathological factors were analyzed. We conducted survival analysis and Cox regression analysis to evaluate the prognosis and independent factors of GC. Co-expressed analysis was also performed. To identify the underlying mechanism, we conducted analyses of differentially expressed genes (DEGs) and functional enrichment. The correlations between COL5A2 expression and immune cell infiltration levels and immune infiltrate gene marker sets were further explored. Additionally, we analyzed the association of COL5A2 expression with immunological checkpoint molecules. Furthermore, the relationship between COL5A2 expression and immunotherapy sensitivity was also investigated.

Results

COL5A2 expression was elevated in GC. More than this, the scRNA-seq analysis revealed that COL5A2 expression had a spatial gradient. The upregulated COL5A2 was associated with worse overall survival. A significant correlation was found between COL5A2 overexpression and age, T classification and clinical stage in GC. COL5A2 was found to be an independent factor for the unfortunate outcome in Cox regression analysis. The co-expressed genes of COL5A2 were associated with tumor stage or poor survival. Enrichment analysis revealed that the DEGs were mainly associated with extracellular matrix (ECM)-related processes, PI3K-AKT signaling pathway, and focal adhesion. GSEA analyses revealed that COL5A2 was associated with tumor progression-related pathways. Meanwhile, COL5A2 expression was correlated with tumor-infiltrating immune cells. Moreover, immunophenoscore (IPS) analysis and PRJEB25780 cohorts showed that patients with low COL5A2 expression were highly sensitive to immunotherapy.

Conclusions

COL5A2 might act as a prognostic biomarker of GC prognosis and immune infiltration and may provide a therapeutic intervention strategy.
Changes in the triglyceride glucose-body mass index estimate the risk of stroke in middle-aged and older Chinese adults: a nationwide prospective cohort study
Authors: Huo Rong-Rui , Zhai Lu , Liao Qian , You Xue-Mei
Published: September 2023

Background

Stroke was reported to be highly correlated with the triglyceride glucose-body mass index (TyG-BMI). Nevertheless, literature exploring the association between changes in the TyG-BMI and stroke incidence is scant, with most studies focusing on individual values of the TyG-BMI. We aimed to investigate whether changes in the TyG-BMI were associated with stroke incidence.

Methods

Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. The exposures were changes in the TyG-BMI and cumulative TyG-BMI from 2012 to 2015. Changes in the TyG-BMI were classified using K-means clustering analysis, and the cumulative TyG-BMI was calculated as follows: (TyG-BMI2012 + TyG-BMI2015)/2 × time (2015–2012). Logistic regressions were used to determine the association between different TyG-BMI change classes and stroke incidence. Meanwhile, restricted cubic spline regression was applied to examine the potential nonlinear association of the cumulative TyG-BMI and stroke incidence. Weighted quantile sum regression was used to provide a comprehensive explanation of the TyG-BMI by calculating the weights of FBG, triglyceride-glucose (TG), and BMI.

Results

Of the 4583 participants (mean [SD] age at baseline, 58.68 [9.51] years), 2026 (44.9%) were men. During the 3 years of follow-up, 277 (6.0%) incident stroke cases were identified. After adjusting for potential confounders, compared to the participants with a consistently low TyG-BMI, the OR for a moderate TyG-BMI with a slow rising trend was 1.01 (95% CI 0.65–1.57), the OR for a high TyG-BMI with a slow rising trend was 1.62 (95% CI 1.11–2.32), and the OR for the highest TyG-BMI with a slow declining trend was 1.71 (95% CI 1.01–2.89). The association between the cumulative TyG-BMI and stroke risk was nonlinear (Passociation = 0.017; Pnonlinearity = 0.012). TG emerged as the primary contributor when the weights were assigned to the constituent elements of the TyG-BMI (weight2012 = 0.466; weight2015 = 0.530).

Conclusions

Substantial changes in the TyG-BMI are independently associated with the risk of stroke in middle-aged and older adults. Monitoring long-term changes in the TyG-BMI may assist with the early identification of individuals at high risk of stroke.
Enhancing HCC Treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition
Authors: Han Rui , Ling Changquan , Wang Yuqian , Lu Lingeng
Published: September 2023

Hepatocellular carcinoma (HCC) is a malignancy with high morbidity and mortality but lacks effective treatments thus far. Although the emergence of immune checkpoint inhibitors in recent years has shed light on the treatment of HCC, a considerable number of patients are still unable to achieve durable and ideal clinical benefits. Therefore, refining the combination of immune checkpoint inhibitors (ICIs) to enhance the therapeutic effect has become a global research hotspot. Several histone deacetylase 2 inhibitors have shown advantages in ICIs in many solid cancers, except for HCC. Additionally, the latest evidence has shown that histone deacetylase 2 inhibition can regulate PD-L1 acetylation, thereby blocking the nuclear translocation of PD-L1 and consequently enhancing the efficacy of PD-1/PD-L1 inhibitors and improving anti-cancer immunity. Moreover, our team has recently discovered a novel HDAC2 inhibitor (HDAC2i), valetric acid (VA), that possesses great potential in HCC treatment as a monotherapy. Thus, a new combination strategy, combining HDAC2 inhibitors with ICIs, has emerged with significant development value. This perspective aims to ignite enthusiasm for exploring the application of ideal HDAC2 inhibitors with solid anti-tumor efficacy in combination with immunotherapy for HCC.
HER3 functions as an effective therapeutic target in triple negative breast cancer to potentiate the antitumor activity of gefitinib and paclitaxel
Authors: Lyu Hui , Shen Fei , Ruan Sanbao , Tan Congcong , Zhou Jundong , Thor Ann D. , Liu Bolin
Published: September 2023

Background

Triple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease.

Methods

Immunohistochemistry was performed to examine the expression of HER3 in TNBC samples. Western blots were used to assess protein expression and activation. Cell proliferation and viability were determined by cell growth (MTS) assays. TCGA databases were analyzed to correlate HER3 mRNA expression with the clinical outcomes of TNBC patients. Specific shRNA was used to knockdown HER3 expression. IncuCyte system was utilized to monitor cell growth and migration. LIVE/DEAD Cell Imaging was to detect live and dead cells. HER3 recognition by our anti-HER3 monoclonal antibody (mAb) 4A7 was verified by ELISA, flow cytometry, and co-immunoprecipitation assays. Orthotopic tumor models were established in nude mice to determine the capability of TNBC cells forming tumors and to test if our mAb 4A7 could potentiate the antitumor activity of paclitaxel in vivo.

Results

Elevated expression of HER3 was observed in approximately half of the TNBC specimens and cell lines tested. Analyses of TCGA databases found that the TNBC patients with high HER3 mRNA expression in the tumors showed significantly worse overall survival (OS) and relapse-free survival (RFS) than those with low HER3 expression. Specific knockdown of HER3 markedly inhibited TNBC cell proliferation and mammosphere formation in vitro and tumor growth in vivo. Our mAb 4A7 abrogated heregulin (a ligand for HER3), but not SDF-1 (a ligand for CXCR4)-induced enhancement of TNBC cell migration. Combinations of 4A7 and the EGFR-tyrosine kinase inhibitor (TKI) gefitinib dramatically decreased the levels of phosphorylated HER3, EGFR, Akt, and ERK1/2 in TNBC cells and potently induced growth inhibition and cell death. Moreover, 4A7 in combination with paclitaxel exerted significant antitumor activity against TNBC in vitro and in vivo.

Conclusions

Our data demonstrate that increased HER3 is an effective therapeutic target for TNBC and our anti-HER3 mAb (4A7) may enhance the efficacy of gefitinib or paclitaxel in TNBC.
Opioid relapse and its predictors among methadone maintenance patients: a multicenter, cross-sectional study in Vietnam
Authors: Nguyen Huong Thi Thanh , Dinh Dai Xuan
Published: September 2023

Background

Opioid relapse, one of the common and severe problems during methadone maintenance treatment, can give rise to poor treatment outcomes. This study measured the opioid relapse rate and its associated factors among methadone maintenance patients in Vietnam.

Methods

Information about the demographic characteristics and social support of 655 patients was collected through direct interviews. Medical records were used to gather data on treatment characteristics. Relapse was determined via urine opioid test results.

Results

The overall relapse rate of patients during treatment was 13.1%. According to the multivariate logistic regression model, living in mountainous areas (adjusted odds ratio (aOR) = 3.63, 95% CI 1.90–7.46) and long duration of drug use in the past (aOR = 1.06, 95% CI 1.03–1.09) were associated with an increase in the odds of opioid relapse. By contrast, living with many family members (aOR = 0.69, 95% CI 0.55–0.85), having longer treatment time (aOR = 0.80, 95% CI 0.73–0.87), and completely adhering to treatment (aOR = 0.38, 95% CI 0.23–0.64) were protective for opioid relapse. As per the univariate analyses, the odds of opioid relapse declined by 25% for each increase of one close friend or relative (OR = 0.75, 95% CI 0.66–0.86). Regarding social support (range score: 0–100), each additional increase of one score was associated with a 1% decrease in the odds of opioid relapse (OR = 0.99, 95% CI 0.98–0.99). Patient sex, education level, occupation type, patient’s monthly income, family’s monthly income, the number of previous treatments, daily methadone dose, comorbidity, and received antiretroviral therapy were not associated with opioid relapse among patients (p > 0.05).

Conclusions

Residence, the role of family and social support, and treatment adherence should be paid more attention to guarantee and enhance the success of methadone maintenance treatment.
HSDL2 knockdown promotes the progression of cholangiocarcinoma by inhibiting ferroptosis through the P53/SLC7A11 axis
Authors: Ma Shuoshuo , Ma Yang , Qi Feiyu , Lei Jiasheng , Chen Fangfang , Sun Wanliang , Wang Dongdong , Zhou Shuo , Liu Zhong , Lu Zheng , Zhang Dengyong
Published: September 2023

Background

Human hydroxysteroid dehydrogenase-like 2 (HSDL2), which regulates cancer progression, is involved in lipid metabolism. However, the role of HSDL2 in cholangiocarcinoma (CCA) and the mechanism by which it regulates CCA progression by modulating ferroptosis are unclear.

Methods

HSDL2 expression levels in CCA cells and tissues were determined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The overall survival and disease-free survival of patients with high vs. low HSDL2 expression were evaluated using Kaplan-Meier curves. The proliferation, migration, and invasion of CCA cells were assessed using Cell Counting Kit-8, colony formation, 5-ethynyl-2′-deoxyuridine DNA synthesis, and transwell assays. The effect of p53 on tumor growth was explored using a xenograft mouse model. The expression of SLC7A11 in patients with CCA was analyzed using immunofluorescence. Ferroptosis levels were measured by flow cytometry, malondialdehyde assay, and glutathione assay. HSDL2-regulated signaling pathways were analyzed by transcriptome sequencing. The correlation between p53 and SLC7A11 was assessed using bioinformatics and luciferase reporter assays.

Results

HSDL2 expression was lower in primary human CCA tissues than in matched adjacent non-tumorous bile duct tissues. HSDL2 downregulation was a significant risk factor for shorter overall survival and disease-free survival in patients with CCA. In addition, HSDL2 knockdown enhanced the proliferation, migration, and invasion of CCA cells. The transcriptome analysis of HSDL2 knockdown cells showed that differentially expressed genes were significantly enriched in the p53 signaling pathway, and HSDL2 downregulation increased SLC7A11 levels. These findings were consistent with the qRT-PCR and western blotting results. Other experiments showed that p53 expression modulated the effect of HSDL2 on CCA proliferation in vivo and in vitro and that p53 bound to the SLC7A11 promoter to inhibit ferroptosis.

Conclusions

HSDL2 knockdown promotes CCA progression by inhibiting ferroptosis through the p53/SLC7A11 axis. Thus, HSDL2 is a potential prognostic marker and therapeutic target for CCA.
Clinical evaluation of radiation-induced sinusitis by MRI-based scoring system in nasopharyngeal carcinoma patients
Authors: Zheng Wenya , Yan Tao , Liu Dongjiao , Chen Geng , Wen Yingjuan , Rao Xiuli , Wang Yizhe , Zheng Huijuan , Yang Jiahong , Peng Hua
Published: September 2023

Objective

To explore the application of magnetic resonance imaging (MRI) in the evaluation of radiation-induced sinusitis (RIS), MRI-based scoring system was used to evaluate the development regularity, characteristics and influencing factors of RIS in nasopharyngeal carcinoma (NPC) patients.

Patients and methods

A retrospective analysis was performed by collecting the clinical and MRI data of 346 NPC patients to analyze the characteristics and prognosis of RIS. The predictive model was constructed according to the influencing factors of RIS.

Results

(1) In the 2-year follow-up after radiotherapy (RT), there was significant change in L-M score in both groups of NPC patients (sinusitis before RT group: p = 0.000 vs. non-sinusitis before RT group: p = 0.000). After 6 months of RT, the L-M scores of the two groups tended to plateau (sinusitis before RT group: p = 0.311 vs. non-sinusitis before RT group: p = 0.469). (2) The prevalence of sinusitis in two groups of NPC patients (without or with sinusitis before RT) was 83% vs. 93%, 91% vs. 99%, 94% vs. 98% at 1, 6 and 24 months after RT, respectively. (3) In the patients without sinusitis before RT, the incidence of sinusitis in maxillary and anterior/posterior ethmoid, sphenoid and frontal sinuses was 87.1%, 90.0%/87.1%, 49.5%, 11.8% respectively, 1 month after RT. (4) A regression model was established according to the univariate and multivariate analysis of the factors related to RIS (smoking history: p = 0.000, time after RT: p = 0.008 and TNM staging: p = 0.040).

Conclusion

(1) RIS is a common complication in NPC patients after RT. This disorder progressed within 6 months after RT, stabilized and persisted within 6 months to 2 years. There is a high incidence of maxillary sinus and ethmoid sinus inflammation in NPC patients after RT. (2) Smoking history, time after RT and TNM staging were significant independent risk factors for RIS. (3) The intervention of the risk factors in the model may prevent or reduce the occurrence of RIS in NPC patients.
Recommendations on palliative care aspects in intensive care medicine
Authors: Michels Guido , Schallenburger Manuela , Neukirchen Martin ,   ICU Palliative Study Group, John Stefan , Janssens Uwe , Raake Philip , Schütt Katharina Andrea , Bauersachs Johann , Barchfeld Thomas , Schucher Bernd , Delis Sandra , Karpf-Wissel Rüdiger , Kochanek Matthias , von Bonin Simone , Erley Christiane M. , Kuhlmann Susanne D. , Müllges Wolfgang , Gahn Georg , Heppner Hans Jürgen , Wiese Christoph H. R. , Kluge Stefan , Busch Hans-Jörg , Bausewein Claudia , Pin Martin
Published: September 2023

Background

The timely integration of palliative care is important for patients suffering from various advanced diseases with limited prognosis. While a German S-3-guideline on palliative care exists for patients with incurable cancer, a recommendation for non-oncological patients and especially for integration of palliative care into intensive care medicine is missing to date.

Method

Ten German medical societies worked on recommendations on palliative care aspects in intensive care in a consensus process from 2018 to 2023.

Results

Based on the german consensus paper, the palliative care aspects of the respective medical disciplines concerning intensive care are addressed. The recommendations partly refer to general situations, but also to specific aspects or diseases, such as geriatric issues, heart or lung diseases, encephalopathies and delirium, terminal renal diseases, oncological diseases and palliative emergencies in intensive care medicine. Measures such as non-invasive ventilation for symptom control and compassionate weaning are also included.

Conclusion

The timely integration of palliative care into intensive care medicine aims to improve quality of life and symptom control and also takes into acccount the often urgently needed support for patients’ highly stressed relatives.
Solitary acrometastasis of the phalanx as initial presentation of an oligometastatic Kirsten rat sarcoma viral oncogene homolog-mutated lung adenocarcinoma: a case report
Authors: Pușcașu Alexandra-Ioana , Moinard-Butot Fabien , Antoni Delphine , Schott Roland , Somme Laura
Published: September 2023

Background

Acrometastasis is an uncommon finding in non-small cell lung cancer and is usually a sign of multimetastatic disease. Few case reports have suggested solitary digital metastasis as the single secondary lesion of oligometastatic non-small cell lung cancer.

Case presentation

This case report describes an unusual presentation of a Kirsten rat sarcoma viral oncogene homolog-mutated lung adenocarcinoma with a solitary bone metastasis in the fourth finger medial phalanx, which was also the first sign of the disease, in a 63-year-old Caucasian female patient. Digital surgical amputation was performed. After histopathological confirmation and radiological exclusion of other secondary lesions, chemoimmunotherapy in a first-line setting was initiated. A partial metabolic response in the primary lung lesion was observed after four cycles. Maintenance therapy is currently being continued.

Conclusion

Solitary digital metastasis is a rare finding in non-small cell lung cancer. Further studies are needed to investigate the mechanisms behind this particular dissemination process.
Immunoproteomic analysis of the serum IgG response to cell wall-associated proteins of Staphylococcus aureus strains belonging to CC97 and CC151
Authors: Drumm Shauna D. , Cormican Paul , Owens Rebecca A. , Mitchell Jennifer , Keane Orla M.
Published: September 2023

CC97 and CC151 are two of the most common Staphylococcus aureus lineages associated with bovine intramammary infection. The genotype of the infecting S. aureus strain influences virulence and the progression of intramammary disease. Strains from CC97 and CC151 encode a distinct array of virulence factors. Identification of proteins elaborated in vivo will provide insights into the molecular mechanism of pathogenesis of these lineages, as well as facilitating the development of tailored treatments and pan-lineage vaccines and diagnostics. The repertoire of genes encoding cell wall-anchored (CWA) proteins was identified for S. aureus strains MOK023 (CC97) and MOK124 (CC151); MOK023 encoded more CWA proteins than MOK124. Serum collected during an in vivo challenge trial was used to investigate whether the humoral response to cell wall proteins was strain-specific. Immunoproteomic analysis demonstrated that the humoral response in MOK023-infected cows predominantly targeted high molecular weight proteins while the response in MOK124-infected cows targeted medium or low molecular weight proteins. Antigenic proteins were identified by two-dimensional serum blotting followed by mass spectometry-based identification of immunoreactive spots, with putative antigens subsequently validated. The CWA proteins ClfB, SdrE/Bbp and IsdA were identified as immunogenic regardless of the infecting strain. In addition, a number of putative strain-specific imunogens were identified. The variation in antigens produced by different strains may indicate that these strains have different strategies for exploiting the intramammary niche. Such variation should be considered when developing novel control strategies including vaccines, therapeutics and diagnostics.
Effects of Bifidobacterium BL21 and Lacticaseibacillus LRa05 on gut microbiota in type 2 diabetes mellitus mice
Authors: Gai Zhonghui , Liao Wenyan , Huang Yue , Dong Yao , Feng Huafeng , Han Mei
Published: September 2023

Gut dysbiosis causes damage to the intestinal barrier and is associated with type 2 diabetes mellitus (T2DM). We tested the potential protective effects of probiotic BL21 and LRa05 on gut microbiota in type 2 diabetes mellitus mice and determined whether these effects were related to the modulation of gut microbiota.Thirty specific pathogen-free C57BL/6J mice were randomly allocated to three groups—the (CTL) control group, HFD/STZ model (T2DM) group, and HFD/STZ-probiotic intervention (PRO) group—and intragastrically administered strains BL21 and LRa05 for 11 weeks. The administration of strains BL21 and LRa05 significantly regulated blood glucose levels, accompanied by ameliorated oxidative stress in mice. The BL21/LRa05-treated mice were protected from liver, cecal, and colon damage. Microbiota analysis showed that the cecal and fecal microbiota of the mice presented significantly different spatial distributions from one another. Principal coordinate analysis results indicated that both T2DM and the BL21/LRa05 intervention had significant effects on the cecal contents and fecal microbiota structure. In terms of the fecal microbiota, an abundance of Akkermansia and Anaeroplasma was noted in the PRO group. In terms of the cecal content microbiota, enrichment of Akkermansia, Desulfovibrio, Bifidobacterium, Lactobacillus, and Limosilactobacillus was noted in the PRO group. The probiotics BL21 and LRa05 prevent or ameliorate T2DM by regulating the intestinal flora and reducing inflammation and oxidative stress. Our results suggest that BL21 and LRa05 colonize in the cecum. Thus, BL21/LRa05 combined with probiotics having a strong ability to colonize in the colon may achieve better therapeutic effects in T2DM. Our study illustrated the feasibility and benefits of the combined use of probiotics and implied the importance of intervening at multiple intestinal sites in T2DM mice.
Antibiotic prescribing to inpatients in Limpopo, South Africa: a multicentre point-prevalence survey
Authors: Mthombeni Tiyani Comfort , Burger Johanita Riétte , Lubbe Martha Susanna , Julyan Marlene
Published: September 2023

Background

Electronic continuous surveillance databases are ideal for monitoring antibiotic use (ABU) in hospitalised patients for antibiotic stewardship programmes (ASP). However, such databases are scarce in low-resource settings. Point prevalence surveys (PPS) are viable alternatives. This report describes ABU and identifies ASP implementation improvement areas in Limpopo Province, South Africa.

Methods

This cross-sectional descriptive study extracted patient-level ABU data from patients’ files using a modified global PPS tool. Data were collected between September and November 2021 at five regional hospitals in Limpopo Province, South Africa. All patients in the wards before 8 a.m. on study days with an antibiotic prescription were included. Antibiotic use was stratified by Anatomic Therapeutic Chemical and Access, Watch, Reserve classifications and presented as frequencies and proportions with 95% confidence intervals (CI). Associations between categorical variables were assessed using the chi-square test. Cramér’s V was used to assess the strength of these associations.

Results

Of 804 inpatients surveyed, 261 (32.5%) (95% CI 29.2–35.7) were prescribed 416 antibiotics, 137 were female (52.5%) and 198 adults (75.9%). One hundred and twenty-two (46.7%) patients received one antibiotic, 47.5% (124/261) received two, and 5.7% (15/261) received three or more antibiotics. The intensive care units had a higher ABU (68.6%, 35/51) compared to medical (31.3%, 120/384) and surgical (28.5%, 105/369) wards (p = 0.005, Cramér’s V = 0.2). Lower respiratory tract infection (27.4%, 104/379), skin and soft tissue infections (SST) (23.5%, 89/379), and obstetrics and gynaecology prophylaxis (14.0%, 53/379) were the common diagnoses for antibiotic prescriptions. The three most prescribed antibiotic classes were imidazoles (21.9%, 91/416), third-generation cephalosporins (20.7%, 86/416) and combination penicillin (18.5%, 79/416). Access antibiotics accounted for 70.2% (292/416) of prescriptions and Watch antibiotics for 29.6% (123/416) (p = 0.110, Cramér’s V = 0.1). Reasons for prescribing and treatment plans were documented in 64.9% (270/416) (95% CI 60.3–69.5) and 21.4% (89/416) (95% CI 17.3–25.3) of prescriptions, respectively.

Conclusions

The study serves as a baseline for ABU surveillance at the five regional hospitals in Limpopo Province. Lack of documentation indicates poor prescribing practices; ASP should address gaps by deploying evidence-based, multifaceted and stepwise interventions.
Competitive endogenous network of circRNA, lncRNA, and miRNA in osteosarcoma chemoresistance
Authors: Qin Shuang , Wang Yuting , Ma Chunhui , Lv Qi
Published: September 2023

Osteosarcoma is the most prevalent and fatal type of bone tumor. Despite advancements in the treatment of other cancers, overall survival rates for patients with osteosarcoma have stagnated over the past four decades Multiple-drug resistance—the capacity of cancer cells to become simultaneously resistant to multiple drugs—remains a significant obstacle to effective chemotherapy. The recent studies have shown that noncoding RNAs can regulate the expression of target genes. It has been proposed that “competing endogenous RNA” activity forms a large-scale regulatory network across the transcriptome, playing important roles in pathological conditions such as cancer. Numerous studies have highlighted that circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) can bind to microRNA (miRNA) sites as competitive endogenous RNAs, thereby affecting and regulating the expression of mRNAs and target genes. These circRNA/lncRNA-associated competitive endogenous RNAs are hypothesized to play significant roles in cancer initiation and progression. Noncoding RNAs (ncRNAs) play an important role in tumor resistance to chemotherapy. However, the molecular mechanisms of the lncRNA/circRNA-miRNA-mRNA competitive endogenous RNA network in drug resistance of osteosarcoma remain unclear. An in-depth study of the molecular mechanisms of drug resistance in osteosarcoma and the elucidation of effective intervention targets are of great significance for improving the overall recovery of patients with osteosarcoma. This review focuses on the molecular mechanisms underlying chemotherapy resistance in osteosarcoma in circRNA-, lncRNA-, and miRNA-mediated competitive endogenous networks.
Prediction of survival and immunotherapy response by the combined classifier of G protein-coupled receptors and tumor microenvironment in melanoma
Authors: Shen Kangjie , Wang Qiangcheng , Wang Lu , Yang Yang , Ren Min , Li Yanlin , Gao Zixu , Zheng Shaoluan , Ding Yiteng , Ji Jiani , Wei Chenlu , Zhang Tianyi , Zhu Yu , Feng Jia , Qin Feng , Yang Yanwen , Wei Chuanyuan , Gu Jianying
Published: September 2023

Background

Melanoma is the deadliest form of skin tumor, and G protein-coupled receptors (GPCRs) play crucial roles in its carcinogenesis. Furthermore, the tumor microenvironment (TME) affects the overall survival (OS) and the response to immunotherapy. The combination of GPCRs and TME from a multi-omics perspective may help to predict the survival of the melanoma patients and their response to immunotherapy.

Methods

Bulk-seq, single-cell RNA sequencing (scRNA-seq), gene mutations, immunotherapy responses, and clinicopathologic feature data were downloaded from public databases, and prognostic GPCRs and immune cells were screened using multiple machine learning algorithms. The expression levels of GPCRs were detected using real-time quantitative polymerase chain reaction (qPCR) in A375 and HaCaT cell lines. The GPCR–TME classifier was constructed and verified using different cohorts and multi-omics. Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and tracking tumor immunophenotype (TIP) were used to identify the key biological pathways among the GPCR–TME subgroups. Then, tumor mutational burden (TMB), vital mutant genes, antigen presentation genes, and immune checkpoints were compared among the subgroups. Finally, the differences in immunotherapy response rates among the GPCR–TME subgroups were investigated.

Results

A total of 12 GPCRs and five immune cell types were screened to establish the GPCR–TME classifier. No significant differences in the expression levels of the 12 GPCRs were found in the two cell lines. Patients with high GPCR score or low TME score had a poor OS; thus, the GPCRlow/TMEhigh subgroup had the most favorable OS. The scRNA-seq result revealed that immune cells had a higher GPCR score than tumor and stromal cells. The GPCR–TME classifier acted as an independent prognostic factor for melanoma. GSEA, WGCNA, and TIP demonstrated that the GPCRlow/TMEhigh subgroup was related to the activation and recruitment of anti-tumor immune cells and the positive regulation of the immune response. From a genomic perspective, the GPCRlow/TMEhigh subgroup had higher TMB, and different mutant genes. Ultimately, higher expression levels of antigen presentation genes and immune checkpoints were observed in the GPCRlow/TMEhigh subgroup, and the melanoma immunotherapy cohorts confirmed that the response rate was highest in the GPCRlow/TMEhigh cohort.

Conclusions

We have developed a GPCR–TME classifier that could predict the OS and immunotherapy response of patients with melanoma highly effectively based on multi-omics analysis.
Characteristics and associated factors of self-reported sexual aggression in the Belgian population aged 16–69
Authors: Schapansky Evelyn , Keygnaert Ines , Vandeviver Christophe
Published: September 2023

Sexual violence is a major public health, societal, and judicial problem worldwide. Studies investigating the characteristics of its perpetrators often rely on samples of convicted offenders, which are biased by low reporting and conviction rates. Based on a self-report study in the Belgian general population aged 16 to 69 (n = 4687), we provide lifetime and past-year prevalence rates of sexual aggression and report the characteristics of the events, including type, target, and the applied coercion strategies. Future research should use behaviourally specific questions that take the perpetrator’s perspective into account to limit interpretation ambiguity which could reduce unintentional non-disclosure of sexual aggression.
Accuracy of lingual straight-wire orthodontic treatment with passive self-ligating brackets and square slot: a retrospective study
Authors: Scisciola Fabrizio , Palone Mario , Scuzzo Giuseppe , Scuzzo Giacomo , Huanca Ghislanzoni Luis T. , Lombardo Luca
Published: September 2023

Objectives

To investigate the accuracy of torque, tip and rotation and linear intra-arch movements yielded by passive self-ligating lingual straight-wire appliances with brackets featuring square slots.

Materials and methods

Twenty-five adult Caucasian patients (16 females and 9 males; mean age 26.5 ± 4.3 years) with Class I or mild Class II head-to-head malocclusion were orthodontically treated via passive lingual self-ligating straight-wire appliances (ALIAS, Ormco, Orange, CA) with no extraction. Records were retrospectively analysed, and digital models of pre-treatment (T0), planned (T1) and achieved (T2) phase were acquired for both arches in each patient via an intraoral scanner (Medit I500 (iScan Medit, Seoul, Korea). VAM software (Vectra, Canfield Scientific, Fairfield, NJ, USA) was used to measure both angular values (torque, tip and rotation) and linear intra-arch widths (between canines, first and second premolars and first and second molars). Measurements were obtained for all the movements investigated for each tooth group (incisors, canines, premolars and molars), by arch (maxillary and mandibular) and for both arches at T0, T1 and T2. The accuracy of angular values was compared using Student's t-test against a hypothetical 100%, and among the various tooth groups by post-hoc tests. Transverse linear measurements were investigated by means of the non-parametric Friedman test. The significance threshold was set at 0.05.

Results

The mean accuracy of angular values was 77.25 ± 7.71% for torque, 78.41 ± 6.17% for tip and 77.99 ± 6.58% for rotation. In all cases, however, there was a significant difference between planned and achieved movements, and accuracy was significantly lower than the hypothetical 100% for all tooth groups, individual arches and dentition (p < 0.001). For intra-arch diameters, the greatest accuracy values were found for the anterior sectors (83.54 ± 5.19% for the maxillary inter-canine distance) and the lowest for the posterior sectors (67.28% for the maxillary inter-second molar distance).

Conclusion

Straight-wire lingual treatment with passive self-ligating appliances featuring with square slot displayed excellent clinical accuracy, albeit with statistical accuracy decreasing antero-posteriorly.
A case of alpha-fetoprotein-positive thymic small cell carcinoma: a case report
Authors: Kobayashi Masao , Funaki Soichiro , Fukui Eriko , Morii Eiichi , Shintani Yasushi
Published: September 2023

Background

An alpha-fetoprotein (AFP)-positive neuroendocrine tumor of the thymus is a rare thoracic malignancy. Few cases of AFP-positive thymic large cell neuroendocrine carcinoma have been reported, with no known previous report of an AFP-positive thymic small cell carcinoma. We encountered a patient with an AFP-positive small cell carcinoma and report here the clinical course.

Case presentation

A 40-year-old man was transferred to our hospital for a large anterior mediastinal tumor and showed an elevated serum AFP level. Computed tomography-guided biopsy results led to diagnosis of small cell carcinoma. Induction chemoradiotherapy was performed before surgery because of pulmonary artery invasion. The response to Induction chemoradiotherapy varied among sites, with the main tumor showing shrinkage and the metastasis site growth. This discrepancy suggested a histologic type unresponsive to or cancer cells potentially resistant to chemotherapy, thus a surgical re-biopsy was performed and histological findings revealed AFP-positive small cell carcinoma. Additional chemotherapy was performed, though could not control cancer progression, and the patient died 8 months after the first medical examination.

Conclusions

Our present clinical experience indicates the importance of histological examination for determining AFP-positive anterior mediastinal tumor treatment. Although AFP-positive neuroendocrine tumor of the thymus is relatively rarer than germ cell carcinoma, differential diagnosis with use of a histological examination should be considered because of the potentially poorer prognosis. The present clinical findings for an AFP-positive neuroendocrine tumor of the thymus case are considered useful for establishing an optimal treatment strategy in the future.
Multifunctional nanozyme-reinforced copper-coordination polymer nanoparticles for drug-resistance bacteria extinction and diabetic wound healing
Authors: Zhao Jiahui , Xu Tengfei , Sun Jichao , Yuan Haitao , Hou Mengyun , Li Zhijie , Wang Jigang , Liang Zhen
Published: September 2023

Background

Drug-resistant bacterial infections in chronic wounds are a persistent issue, as they are resistant to antibiotics and can cause excessive inflammation due to generation of reactive oxygen species (ROS). An effective solution would be to not only combat bacterial infections but also scavenge ROS to relieve inflammation at the wound site. Scaffolds with antioxidant properties are attractive for their ability to scavenge ROS, and there is medical demand in developing antioxidant enzyme-mimicking nanomaterials for wound healing.

Methods

In this study, we fabricated copper-coordination polymer nanoparticles (Cu-CPNs) through a self-assembly process. Furthermore, ε-polylysine (EPL), an antibacterial and cationic polymer, was integrated into the Cu-CPNs structure through a simple one-pot self-assembly process without sacrificing the glutathione peroxidase (GPx) and superoxide dismutase (SOD)-mimicking activity of Cu-CPNs.

Results

The resulting Cu-CPNs exhibit excellent antioxidant propertiesin mimicking the activity of glutathione peroxidase and superoxide dismutase and allowing them to effectively scavenge harmful ROS produced in wound sites. The in vitro experiments showed that the resulting Cu-CPNs@EPL complex have superior antioxidant properties and antibacterial effects. Bacterial metabolic analysis revealed that the complex mainly affects the cell membrane integrity and nucleic acid synthesis that leads to bacterial death.

Conclusions

The Cu-CPNs@EPL complex has impressive antioxidant properties and antibacterial effects, making it a promising solution for treating drug-resistant bacterial infections in chronic wounds. The complex’s ability to neutralize multiple ROS and reduce ROS-induced inflammation can help relieve inflammation at the wound site.

Graphical Abstract

Schematic illustration of the ROS scavenging and bacteriostatic function induced by Cu-CPNs@EPL nanozyme in the treatment of MRSA-infected wounds.
Does the painDETECT questionnaire identify impaired conditioned pain modulation in people with musculoskeletal pain? – a diagnostic accuracy study
Authors: Bittencourt Juliana Valentim , Leivas Eduardo Gallas , de Sá Ferreira Arthur , Nogueira Leandro Alberto Calazans
Published: September 2023

Background

People with neuropathic-like symptoms had more unfavourable pain features than people with nociceptive. Moreover, deficient conditioned pain modulation is common in people with neuropathic-like symptoms. PainDETECT questionnaire have been used to assess the central sensitisation sign and symptoms. However, whether the painDETECT questionnaire can identify the conditioned pain modulation's impairment is still unknown. Therefore, the current study aimed to evaluate the diagnostic accuracy of the painDETECT questionnaire in detecting the impairment of conditioned pain modulation in people with musculoskeletal pain.

Methods

We conducted a diagnostic accuracy comparing the painDETECT questionnaire (index method) with the cold pressor test, the psychophysical test used to assess the conditioned pain modulation (reference standard). We determined diagnostic accuracy by calculating sensitivity, specificity, predictive values, and likely hood ratios.

Results

We retrospectively enrolled 308 people with musculoskeletal pain in outpatient departments. Most participants were female (n 20 = 220, 71.4%) and had a mean age of 52.2 (± 15.0) years. One hundred seventy-three (56.1%) participants were classified as nociceptive pain, 69 (22.4%) as unclear, and 66 (21.4%) as neuropathic-like symptoms. According to the cold pressor test, 60 (19.4%) participants presented impairment of conditioned pain modulation. The cutoff point of 12 of the painDETECT questionnaire showed values of diagnostic accuracy below 70% compared to the cold pressor test, except for a negative predictive value [76.9 95% Confidence Interval (CI) 71.7 to 81.5]. The cutoff point 19 showed high specificity (78.6%, 95% CI 73.0 to 83.5), high negative predictive value (80.5%, 95% CI 78.1 to 82.7), and accuracy of 67.5% compared to the cold pressor test.

Conclusion

The painDETECT questionnaire seems valuable for ruling out people with musculoskeletal pain and impairment of conditioned pain modulation.
MR-guided laser interstitial thermal therapy for drug-resistant lesional epilepsy: a single-center experience
Authors: Niu Hongchuan , Li Kai , Liang Xiaoning , Kong Desheng , Li Zongze , Sun Fengqiao , Liu Xianzeng , Xu Zongsheng , Wei Xuejiao , Lan Shuang , Lu Changyu
Published: September 2023

Background

To describe and report the efficacy and safety of MR-guided laser interstitial thermal therapy (MRgLITT) in the treatment of drug-resistant epilepsy.

Methods

A retrospective review of all MRgLITT procedures in our hospital was performed. All procedures were performed using a surgical laser ablation system. Demographic and outcome data were compiled and analyzed.

Results

A total of 19 patients underwent MRgLITT procedures from June 2021 to November 2021. The average age at surgery was 18.1 years (3–61.4 years). The average length of hospitalization post-surgery was 4.95 days (4–7 days). Surgical substrates included 8 patients with hypothalamic hamartomas, 5 with medial temporal lobe epilepsy, 3 with deep focal cortical dysplasia, 1 with tuberous sclerosis, 1 with a cavernous malformation, and 1 with Lennox–Gastaut syndrome who underwent anterior corpus callosotomy. Complications occurred in three patients. After an average follow-up of 1 year, 6 patients were seizure-free (Engel I, 31.6%), 1 had significant seizure control (Engel II, 5.3%), 7 had seizure control (Engel III, 36.8%), and 5 had no improvement in their seizures (Engel IV, 26.3%). Fisher’s exact tests did not reveal statistical significance for the association between Engel class outcome and epileptic disease.

Conclusion

This study confirmed that MRgLITT, as a method for treating drug-resistant epilepsy, is minimally invasive, safe, and efficient and that it can reduce the incidence of surgery-related complications.
Current therapeutic strategies for acute kidney injury
Authors: Negi Shigeo , Wada Tatsuya , Matsumoto Naoya , Muratsu Jun , Shigematsu Takashi
Published: September 2023

Acute kidney injury (AKI) is an emerging public health problem worldwide and is associated with high morbidity and mortality. The high mortality rate can be attributed to the lack of pharmacological therapies to prevent and treat AKI. Renal replacement therapy (RRT) plays a pivotal role in the treatment of patients with severe AKI. However, the mortality rate of patients with AKI requiring RRT exceeds 50%. Although studies on RRT for AKI have begun to resolve some of the associated problems, many issues remain to be addressed. Notably, the optimal timing of the initiation of RRT for AKI is still being debated. Recently, new therapeutic strategies for AKI have been developed. Angiotensin II and recombinant alkaline phosphatase treatment are expected to improve the clinical outcomes of patients with distributive and vasodilatory shock. Moreover, mitochondrial-targeted agents have been developed for the treatment of patients with AKI. This review is focused on the optimal timing of RRT for AKI and the new pharmacological interventions and therapies for AKI.
Sphenopalatine ganglion block with or without greater occipital nerve block for treatment of obstetric post-dural puncture headache after spinal anesthesia: randomized controlled trial
Authors: Elshafei Amr Shaaban , Mowafy Sherif M. S.
Published: September 2023

Background

Conservative treatments of post-dural puncture headache (PDPH) may be unsuccessful, and the relief that is provided is frequently insufficient. This study aimed to meticulously explore the analgesic efficacy of the sphenopalatine ganglion (SPG) block when administered alone or in conjunction with the greater occipital nerve block (GONB) for the purpose of treating PDPH and with the aid of transcranial Doppler (TCD) to evaluate the cerebral hemodynamics before and after the block.

This study was conducted on 63 women with post-partum PDPH randomized into the following: control group (Group C = 21 participants), received conservative management; SPG block group (Group S = 21 participants), received conservative management with SPG block; and combined nerve and ganglion block group (Group NAG = 21 participants), received conservative management with SPG block and ultrasound guided GONB. Visual analog score (VAS), modified Lybecker score, and transcranial Doppler (TCD) measures were used to determine PDPH severity at 0 (baseline), 1, 6, and 24 h. Additionally, the three groups’ needs for EBP were noted.

Results

VAS and modified Lybecker scores at 1, 6, and 24 h were statistically significantly lower in S and NAG groups compared to the control group with no statistically significant difference between S and NAG groups. With TCD, the mean velocity (MV) was significantly lower at 1, 6, and 24 h compared to baseline reading in both S and NAG groups. Also, the pulsatility index (PI) was statistically higher at 1, 6, and 24 h compared to baseline readings in S and NAG groups. There was no statistically significant difference regarding the need for EBP.

Conclusions

In terms of headache relief or the need for EBP, there is no difference between individual SPG block or combined SPG block and GONB in the treatment of PDPH.
Evaluation of thyromental height test as a single anatomical measure for prediction of difficult laryngoscopy: a prospective observational study
Authors: Bhiwal Anil Kumar , Sharma Charu , Tripathi Anuj , BK Aakansha , Choudhary Vidhu , Gupta Sunanda
Published: September 2023

Background

Preoperative airway assessment is essential to predict difficult airway so that adequate planning could be made to secure the airway. Various airway tests have been devised to improve diagnostic accuracy but none of the tests individually have proven to be adequate. Recently, a new airway predictor thyromental height test (TMHT) appears to be a more accurate predictor of difficult laryngoscopy than the existing anatomical measurements. The aim of this study is to evaluate the accuracy of the TMHT and compare it with various screening tests to determine whether TMHT can prove to be a more comprehensive and accurate test for predicting difficult laryngoscopy. Total 150 patients aged > 18 years of either sex with American Society of Anaesthesiologist physical status I—III scheduled for elective surgery under general anaesthesia requiring tracheal intubation were included in this prospective observational study. All patients were subjected to a preoperative airway assessment test including TMHT, modified Mallampati test, upper lip bite test, interincisior gap, thyromental distance and sternomental distance. Intraoperatively direct laryngoscopy was done and the grading of laryngoscopic view was done according to CL.

Results

The preoperative data and CL grading were used to evaluate the accuracy of TMHT and compared the sensitivity, specificity, positive and negative predictive value with other tests.

Twenty six (17.33%) patients had difficult laryngoscopy and 18 patients (12%) required bougie/stylet to facilitate intubation. TMHT had the highest sensitivity (76.92%), specificity (98.38%), PPV (90.90%), NPV (95.31%) and accuracy (94.67%) when compared to other tests.

Conclusions

TMHT is a simple bedside test with higher sensitivity and specificity for predicting difficult laryngoscopy as compared to other screening tests.Future study should be done to define ethinicity, race, age groups and gender specific cut off values of TMHT for accurate validation of prediction in difficult laryngoscopy.