Dual colorimetric platforms for direct detection of glyphosate based on Os-Rh nanozyme with peroxidase-like activity.

BACKGROUND: To minimize the impact of pesticide residues in food on human health, it is necessary to enhance their detection. Recently, many nanozyme-based colorimetric methods for pesticides detection have been developed, however, they often required the assistance of natural enzymes, which made the process and result of methods susceptible to the stability and activity of natural enzymes. To overcome these drawbacks, methods for direct detection of pesticides using nanozymes have been developed, and there are few studies in this field currently. Thus, it is of great research and practical significance to develop more nanozymes-based colorimetric methods for direct detection of pesticides. RESULTS: Dual colorimetric platforms based on Os-Rh nanozyme with excellent peroxidase-like activity were constructed for directly detection of glyphosate in this work. Results showed that glyphosate was able to sensitively and selectively inhibit the peroxidase-like activity of Os-Rh nanozyme through hindering the decomposition of H2O2 by Os-Rh nanozyme to produce HO∙. Based on this, the dual colorimetric platforms achieved highly sensitive detection for glyphosate over a wide linear concentration range (50-1000 µg L-1 in solution platform and 200-1000 µg L-1 in paper platform), with the detection limits of 28.37 µg L-1 in solution platform and 400 µg L-1 (naked-eye detection limit)/123.25 µg L-1 (gray scale detection limit) in paper platform, respectively. Moreover, the dual colorimetric platforms possessed satisfactory reliability and accuracy for practical applications, and has been successfully applied to the detection of real samples with the spiked recoveries of 92.78-102.75 % and RSD of 1.17-3.88 %. SIGNIFICANCE: The dual colorimetric platforms for glyphosate direct detection based on Os-Rh nanozyme developed in this work not only owned considerable practical application potential, but also could provide more inspirations and ideas for the rational design and development of colorimetric sensing methods for the rapid detection of pesticides based on nanozymes.

A useful mTORC1 signaling-related RiskScore model for the personalized treatment of osteosarcoma patients by using the bulk RNA-seq analysis.

AIMS: This research developed a prognostic model for OS patients based on the Mechanistic Target of Rapamycin Complex 1 (mTORC1) signature. BACKGROUND: The mTORC1 signaling pathway has a critical role in the maintenance of cellular homeostasis and tumorigenesis and development through the regulation of cell growth, metabolism and autophagy. However, the mechanism of action of this signaling pathway in Osteosarcoma (OS) remains unclear. OBJECTIVE: The datasets including the TARGET-OS and GSE39058, and 200 mTORC1 genes were collected. METHODS: The mTORC1 signaling-related genes were obtained based on the Molecular Signatures Database (MSigDB) database, and the single sample gene set enrichment analysis (ssGSEA) algorithm was utilized in order to calculate the mTORC1 score. Then, the WGCNA were performed for the mTORC1-correlated gene module, the un/multivariate and lasso Cox regression analysis were conducted for the RiskScore model. The immune infiltration analysis was performed by using the ssGSEA method, ESTIMATE tool and MCP-Count algorithm. KM survival and Receiver Operating Characteristic (ROC) Curve analysis were performed by using the survival and timeROC package. RESULTS: The mTORC1 score and WGCNA with ß = 5 screened the mTORC1 positively correlated skyblue2 module that included 67 genes, which are also associated with the metabolism and hypoxia pathways. Further narrowing of candidate genes and calculating the regression coefficient, we developed a useful and reliable RiskScore model, which can classify the patients in the training and validation set into high and low-risk groups based on the median value of RiskScore as an independent and robust prognostic factor. High-risk patients had a significantly poor prognosis, lower immune infiltration level of multiple immune cells and prone to cancer metastasis. Finally, we a nomogram model incorporating the metastasis features and RiskScore showed excellent prediction accuracy and clinical practicability. CONCLUSION: We developed a useful and reliable risk prognosis model based on the mTORC1 signaling signature.

Philosophies And Surgical Techniques on Os Odontoideum Treatment with Literature Review.

Introduction: Os-odontoideum is a rare condition described radiographically and clinically as a congenital anomaly of the second cervical vertebra (axis). It is a smooth, independent ossicle of variable size and shape separated from the base of a shortened odontoid process by an obvious gap, with no osseous connection to the body of C2. Materials and Methods: This study reviewed the literature on OO to evaluate its etiology, clinical presentations, differential diagnosis, imaging modalities, and outcomes in the management of asymptomatic and symptomatic cases of Os Odontoideum. Key articles from PubMed, EMBASE, Google Scholar, and Cochrane were searched. Discussion: Considering etiology, the traumatic hypothesis is favoured over the congenital hypothesis as per recent literature on OO. Clinical presentation varies from asymptomatic to mild neck pain to severe myelopathy and neurodeficit. Various C1-C2 instrumentation and fusion techniques like wiring, trans articular screw and laminar screws have been described with success rates. Conclusion: Os odontoideum is a rare condition with limited existing literature. Considering the significant risks involved if conservative management opts, like severe neuro deficit to sudden death on trivial trauma and the recent improvement of imaging tools helping to understand the pathology of the disease, surgery can be indicated even in an incidentally detected os odontoideum. However, a case-by-case approach can be considered for stable asymptomatic patients depending on factors such as age, activity level, comorbidities, syndromic association, and radiographic findings.

Polycyclic aromatic hydrocarbons in coral reefs from Southwestern Atlantic: A seascape approach using tissue and skeleton of the coral Montastraea cavernosa (Cnidaria; Scleractinia).

Coastal marine ecosystems, such as coral reefs, are severely threatened by climate changes, overexploitation, and marine pollution. Particularly, environmental pollution caused by petroleum-derived substances is poorly studied in coral reefs in tropical developing countries, with a total absence of data about these contaminants in some regions. In this work, we determined the levels of conventional and unconventional PAHs in the tissue and skeleton of the coral Montastraea cavernosa in a seascape scale of the Southwest Atlantic. We sampled in 12 coral reefs adjacent to the coast along approximately 200 km. We found 14 PAHs, 2 Oxy-PAHs, and 15 Nitro-PAHs in the samples, and among them, benzo[a]pyrene, chrysene, benzo[a]anthracene, benzo[k]fluoranthene, indeno[1,2,3-c,d]pyrene and dibenz[a,h]anthracene, which are mutagenic, teratogenic and carcinogenic substances. Skeletons presented predominantly lower quantities of ∑PAHs than the respective tissue, except for the skeletons from one reef severely impacted by oil spills. The ∑PAHs levels were lower in a bay near an urbanized region than in open sea reefs. Diagnostic ratios indicate mixogenic sources, with the predominance of petrogenic origin. Our study provides the first occurrence of PAHs, Nitro-PAHs, and Oxy-PAHs distribution in corals from the Southwest Atlantic Ocean, and we expect that these data will help to evaluate any future impacts and management of this ecosystem.

Paraneoplastic Syndrome Prevalence and Survival in Racially-Diverse Cohort With Renal Cell Carcinoma.

INTRODUCTION: The prevalence of preoperative paraneoplastic syndromes (PNS) in renal cell carcinoma (RCC) is poorly understood. Many laboratory abnormalities representative of PNS have demonstrated prognostic value when incorporated into predictive survival models in RCC. We sought to characterize the relationship between baseline prevalence of PNS with overall survival (OS) and cancer-specific survival (CSS) in RCC patients following nephrectomy. METHODS: Our prospectively maintained nephrectomy database was retrospectively reviewed for any stage, major histology RCC patients that underwent surgery from 2000 to 2022. Baseline laboratory values within 90 days (closest used) were required. Presence of PNS was defined according to established laboratory cutoffs. Kaplan-Meier curves estimated survival rates, and multivariable Cox proportional hazards models examined the association between PNS with OS and CSS following nephrectomy. RESULTS: 2599 patients were included with listed staging: 1494 Stage I; 180 Stage II; 616 Stage III; 306 Stage IV. Proportion of patients presenting with >1 PNS significantly increased from stage I (31.3%) to stage IV (74.2%) RCC (P < .001). Elevated C-reactive protein was the most prevalent PNS (45.4%). On multivariable analysis, the presence of >1 PNS was associated with higher risk of all-cause (HR 2.09; P < .001) and cancer-specific mortality (HR 2.55; P < .001). The 10-year OS estimates as reported: 65.2% (no PNS), 52.3% (1 PNS), 36.6% (>1 PNS); and 10-year CSS estimates: 88.3% (no PNS), 79.3% (1 PNS), 61.6% (>1 PNS). DISCUSSION: Increased prevalence of PNS in major histology RCC was associated with a significant increase in the risk of all-cause and cancer-specific mortality even when accounting for patient and disease characteristics.

Single-center clinical experience of extended sleeve lobectomy (ESL) versus standard sleeve lobectomy (SL).

Background: Sleeve lobectomy (SL) and extended SL (ESL), which aim to preserve pulmonary function and enhance the quality of life of patients while ensuring oncological outcomes, are valuable surgical options for the treatment of centrally located non-small cell lung cancer (NSCLC). This study aimed to compare perioperative adverse events and long-term survival between SL and ESL in NSCLC patients, providing a comprehensive review of surgical outcomes, complications, and survival to assess the roles of SL and ESL in thoracic oncology. Methods: This single-center retrospective study assessed the outcomes of NSCLC patients who underwent SL or ESL from June 2014 to January 2022. The patients were selected based on specific inclusion criteria, and statistical analyses were conducted to examine the postoperative outcomes, overall survival (OS), and disease-free survival (DFS) of the patients. Results: A total of 218 patients met the inclusion criteria. Among 218 patients, 33 underwent ESL and 185 underwent SL. Compared to SL, ESL was associated with longer operative times and higher R0 resection rates (93.9% vs. 78.8%, P=0.047). Despite the higher complexity of ESL compared to SL, there were no significant differences in the perioperative complications or mortality rates between the groups. Survival analysis was conducted on the propensity score matching (PSM) data, the results demonstrated superior OS and DFS in the ESL group compared to the SL group. Advanced age, more advanced nodal (N) status, and non-R0 resection were significant predictors of poorer prognosis. Conclusions: ESL is a feasible and effective alternative for treating centrally located NSCLC, with better R0 resection rates and comparable survival outcomes to SL, without increasing the risk of grade III-IV complications. Further studies with larger cohorts need to be conducted to validate these findings and refine the surgical techniques.

FOSL1 promotes stem cell­like characteristics and anoikis resistance to facilitate tumorigenesis and metastasis in osteosarcoma by targeting SOX2.

Metastasis is the leading cause of cancer­related death in osteosarcoma (OS). OS stem cells (OSCs) and anoikis resistance are considered to be essential for tumor metastasis formation. However, the underlying mechanisms involved in the maintenance of a stem­cell phenotype and anoikis resistance in OS are mostly unknown. Fos­like antigen 1 (FOSL1) is important in maintaining a stem­like phenotype in various cancers; however, its role in OSCs and anoikis resistance remains unclear. In the present study, the dynamic expression patterns of FOSL1 were investigated during the acquisition of cancer stem­like properties using RNA sequencing, PCR, western blotting and immunofluorescence. Flow cytometry, tumor­sphere formation, clone formation assays, anoikis assays, western blotting and in vivo xenograft and metastasis models were used to further investigate the responses of the stem­cell phenotype and anoikis resistance to FOSL1 overexpression or silencing in OS cell lines. The underlying molecular mechanisms were evaluated, focusing on whether SOX2 is crucially involved in FOSL1­mediated stemness and anoikis in OS. FOSL1 expression was observed to be upregulated in OSCs and promoted tumor­sphere formation, clone formation and tumorigenesis in OS cells. FOSL1 expression correlated positively with the expression of stemness­related factors (SOX2, NANOG, CD117 and Stro1). Moreover, FOSL1 facilitated OS cell anoikis resistance and promoted metastases by regulating the expression of apoptosis related proteins BCL2 and BAX. Mechanistically, FOSL1 upregulated SOX2 expression by interacting with the SOX2 promoter and activating its transcription. The results also showed that SOX2 is critical for FOSL1­mediated stem­like properties and anoikis resistance. The current findings indicated that FOSL1 is an important regulator that promotes a stem cell­like phenotype and anoikis resistance to facilitate tumorigenesis and metastasis in OS by regulating the transcription of SOX2. Thus, FOSL1 might represent an attractive target for therapeutic interventions in OS.

A novel nomogram based on the number of positive lymph nodes can predict the overall survival of patients with pancreatic head cancer after radical surgery.

BACKGROUND: This study aimed to construct a novel nomogram based on the number of positive lymph nodes to predict the overall survival of patients with pancreatic head cancer after radical surgery. MATERIALS AND METHODS: 2271 and 973 patients in the SEER Database were included in the development set and validation set, respectively. The primary clinical endpoint was OS (overall survival). Univariate and multivariate Cox regression analyses were used to screen independent risk factors of OS, and then independent risk factors were used to construct a novel nomogram. The C-index, calibration curves, and decision analysis curves were used to evaluate the predictive power of the nomogram in the development and validation sets. RESULTS: After multivariate Cox regression analysis, the independent risk factors for OS included age, tumor extent, chemotherapy, tumor size, LN (lymph nodes) examined, and LN positive. A nomogram was constructed by using independent risk factors for OS. The C-index of the nomogram for OS was 0.652 [(95% confidence interval (CI): 0.639-0.666)] and 0.661 (95%CI: 0.641-0.680) in the development and validation sets, respectively. The calibration curves and decision analysis curves proved that the nomogram had good predictive ability. CONCLUSIONS: The nomogram based on the number of positive LN can effectively predict the overall survival of patients with pancreatic head cancer after surgery.

FAM109B plays a tumorigenic role in low-grade gliomas and is associated with tumor-associated macrophages (TAMs).

BACKGROUND: Family with sequence similarity 109, member B (FAM109B) is involved in endocytic transport and affects genetic variation in brain methylation. It is one of the important genes related to immune cell-associated diseases. In the tumor immune system, methylation can regulate tumor immunity and influence the maturation and functional response of immune cells. Whether FAM109B is involved in tumor progression and its correlation with the tumor immune microenvironment has not yet been disclosed. METHODS: A comprehensive pan-cancer analysis of FAM109B expression, prognosis, immunity, and TMB was conducted. The expression, clinical features, and prognostic value of FAM109B in low-grade gliomas (LGG) were evaluated using TCGA, CGGA, and Gravendeel databases. The expression of FAM109B was validated by qRT-PCR, immunohistochemistry (IHC), and Western blotting (WB). The relationship between FAM109B and methylation, Copy Number Variation (CNV), prognosis, immune checkpoints (ICs), and common chemotherapy drug sensitivity in LGG was explored through Cox regression, Kaplan-Meier curves, and Spearman correlation analysis. FAM109B levels and their distribution were studied using the TIMER database and single-cell analysis. The potential role of FAM109B in gliomas was further investigated through in vitro and in vivo experiments. RESULTS: FAM109B was significantly elevated in various tumor types and was associated with poor prognosis. Its expression was related to aggressive progression and poor prognosis in low-grade glioma patients, serving as an independent prognostic marker for LGG. Glioma grade was negatively correlated with FAM109B DNA promoter methylation. Immune infiltration and single-cell analysis showed significant expression of FAM109B in tumor-associated macrophages (TAMs). The expression of FAM109B was closely related to gene mutations, immune checkpoints (ICs), and chemotherapy drugs in LGG. In vitro studies showed increased FAM109B expression in LGG, closely related to cell proliferation. In vivo studies showed that mice in the sh-FAM109B group had slower tumor growth, slower weight loss, and longer survival times. CONCLUSIONS: FAM109B, as a novel prognostic biomarker for low-grade gliomas, exhibits specific overexpression in TAMs and may be a potential therapeutic target for LGG patients.

Os subtibiale displacement secondary to pronation-external rotation ankle injury: A case report.

Os subtibiale is a rare accessory ossicle of the ankle, considered not of clinical significance. But its presence in trauma patients may cause misdiagnosis as malleolar fracture and over-treatment. Because the ossicle is attached to the deltoid ligament, ankle trauma that cause medial compartment injury may detach os subtibiale from medial malleolus. In these situations, MR imaging may help to diagnose the deltoid injury, demonstrate the features of the ossicle, and guide treatment.

The prevalence and anatomy of accessory navicular bone: a meta-analysis.

PURPOSE: There have been over 40 descriptions of the common developmental variants of the accessory ossicles of the feet. Although predominantly asymptomatic, they sometimes may be linked to painful conditions. One of the most common accessory ossicles in the foot is the accessory navicular bone (AN), located on the medial side of the foot. Our research provides a first meta-analysis on this topic that establishes its frequency by contrasting 39 studies from across the globe. METHODS: Up to February 2024, PubMed and Embase databases were thoroughly searched for research on the AN. Eligible data regarding AN prevalence was extracted. This study strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 39 studies, 11,015 patients, and 36,837 feet were analyzed in our study. The pooled prevalence estimate (PPE) of AN was found to be 17.5% (95%CI: 11.5-25.7) and 12.6% (95%CI: 10.1-15.5) in patients and feet analyses, respectively. Accessory navicular occurred bilaterally in 50.0% of patients, with similar distribution in gender-based groups (21.1% of males and 22.0% of females were confirmed with AN). Accessory navicular was most prevalent in the East Asian population (38.4%) and least prevalent in North Americans (8.0%). No significant differences in AN prevalence were found when comparing different imaging modalities (X-ray and cadaver dissection). CONCLUSION: Accessory navicular is a common finding in imaging studies. Its prevalence depends on the population covered by the study but is not affected by the patient's gender or the imaging modality utilized for AN assessment.

A synovial cyst-induced vertebral artery dissection in bow hunter's stroke: illustrative case.

BACKGROUND: Bow hunter's stroke (BHS) is a rare condition characterized by occlusion of the vertebral artery (VA) due to a head rotation. BHS typically results from neck hyperrotation, often due to anatomical factors. The authors present a case of BHS in a young male patient exacerbated by os odontoideum (OD), resulting in atlantoaxial dislocation, which ultimately led to VA dissection. OBSERVATIONS: A man in his 20s presented with persistent dizziness and nausea and initially received a diagnosis of a brain infarction. However, imaging revealed VA dissection caused by an OD with an associated synovial cyst. Surgical intervention, specifically atlantoaxial posterior fixation, resolved the instability and allowed for natural regression of the synovial cysts, preventing further vascular events. In this case, the OD with atlantoaxial dislocation was identified as the causative factor for BHS. The coexistence of a synovial cyst was a unique finding, likely triggered by chronic irritation caused by the OD. LESSONS: This case emphasizes the importance of thorough cervical spinal evaluation in young patients presenting with posterior circulation stroke. https://thejns.org/doi/10.3171/CASE2487.

Computed tomography (CT)-based skeletal muscle vertebral-related index to assess low muscle mass in patients with non-small cell lung cancer.

Background: Patients with lung cancer accompanied by sarcopenia may have a poor prognosis. Normally, low muscle mass associated with sarcopenia is assessed using the skeletal muscle index (SMI). It remains unclear whether the standardized skeletal muscle area (SMA) using 2-dimensional (2D) vertebral metrics (called the skeletal muscle vertebral related index, SMVI) could substitute for SMI when it is missing. The aim of this study was to investigate the feasibility of SMVI as an alternative to SMI, and their associations with overall survival (OS) in patients with non-small cell lung cancer (NSCLC). Methods: In this single-center study, a retrospective analysis was conducted on 433 NSCLC patients who underwent computed tomography (CT) scans. At the third lumbar vertebra (L3) level, measurements were taken for SMA, vertebral body area, transverse vertebral diameter (TVD), longitudinal vertebral diameter (LVD), and vertebral height (VH). The 4 SMVIs were skeletal muscle vertebral ratio (SMVR) (SMA/vertebral body area), skeletal muscle transverse vertebral diameter index (SMTVDI) (SMA/TVD2), skeletal muscle longitudinal vertebral diameter index (SMLVDI) (SMA/LVD2), and skeletal muscle vertebral height index (SMVHI) (SMA/VH2). The patients were categorized into low and high muscle mass groups based on SMI, and the differences in SMVIs between the 2 groups were compared to assess their correlation with SMI. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were utilized to assess the discriminatory ability. Kaplan-Meier curves were employed to compare the survival disparity between the 2 groups. Results: We included 191 male and 242 female patients in this study. Compared to the high muscle mass group, patients in the low muscle mass group exhibited significantly lower SMVR, SMTVDI, SMLVDI, and SMVHI (all P<0.05). All 4 SMVIs showed a positive correlation with SMI, with Spearman correlation coefficients of 0.83, 0.76, 0.75, and 0.67, respectively (all P<0.001). The AUC for diagnosing low muscle mass was higher than 0.8 for all 4 SMVI parameters. The Kaplan-Meier curve revealed that the low-risk group had a better survival probability than the high-risk group in the SMVR, SMTVDI, and SMLVDI. Conclusions: The SMVI functions as an alternative metric for evaluating skeletal muscle mass in the assessment of NSCLC based on SMI.

Jejunostomy feeding plus oral feeding versus intravenous nutrition plus oral feeding after esophageal cancer resection: a comparative retrospective cohort study.

Background: There are multiple choices for the nutritional management mode after esophageal cancer surgery. Currently, there is still controversy regarding which nutritional management mode has an impact on the postoperative recovery and overall survival (OS) of patients. This study aims to compare the differences between two commonly used clinical nutritional management modes: jejunostomy feeding plus oral intake (JF plus OI) and intravenous nutrition plus oral intake (IN plus OI), in terms of short-term efficacy and 3-year OS, in order to further explore the optimal mode of enteral nutrition management after esophageal cancer surgery. Methods: We evaluated esophageal cancer patients who underwent radical surgery at Union Hospital of Fujian Medical University between January 1, 2010 and January 1, 2020. The purpose of this analysis was to compare the perioperative complications, Nutritional Risk Screening 2002 (NRS2002) nutritional scores at 1 week, 2 weeks, 1 month, and 3 months after surgery, as well as the 3-year OS rates, between two different nutritional management approaches: JF plus OI and IN plus OI following esophageal cancer surgery. Results: Among the 822 patients included, 668 and 154 patients belonged to JF plus OI and IN plus OI groups, respectively. After propensity score matching, 149 patients per group were evaluated. The amount of gastric drainage fluid was higher in the IN plus OI group (P<0.05), and the incidence of postoperative gastrointestinal emptying disorder and intestinal obstruction was significantly higher in the JF plus OI group (P<0.05). The IN plus OI group had a higher incidence of perioperative hypoproteinemia (P<0.05), and a higher risk of malnutrition in 2 weeks after surgery (P<0.05). The 3-year OS was not significantly different (P>0.05). Conclusions: JF plus OI may be the preferable nutritional management approach after esophageal cancer resection as it can potentially reduce perioperative nutritional deficiency. However, attention should be paid to the risk of gastrointestinal emptying and intestinal obstruction associated with JF.

Efficacy and survival outcome of allogeneic stem-cell transplantation in multiple myeloma: meta-analysis in the recent 10 years.

Introduction: Allogeneic hematopoietic cell transplantation (alloHCT) possessed direct cytotoxicity and graft-versus-multiple myeloma effect (GvMM). Growing trials have shown survival benefits of performing alloHCT in both newly diagnosed and relapsed MM. Methods: We aimed to provide a comprehensive analysis in the recent 10 years to verify the efficacy and survival outcome of alloHCT in MM patients. A total of 61 studies which provide data between 14/04/2013 and 14/04/2023 and a total of 15,294 data from MM patients who had undergone alloSCT were included in our study. The best response rates (CR, VGPR, PR) and survival outcomes (1-, 2-, 3-,5-, and 10-year OS, PFS, NRM) were assessed. We further conducted meta-analysis in the NDMM/frontline setting and RRMM/salvage setting independently. Results: The pooled estimate CR, VGPR, and PR rates were 0.45, 0.21, and 0.24, respectively. The pooled estimates of 1-, 2-, 3-, 5-, and 10-year OS were 0.69, 0.57, 0.45, 0.45, and 0.36, respectively; the pooled estimates of 1-, 2-, 3-, 5-, and 10-year PFS were 0.47, 0.35, 0.24, 0.25, and 0.28, respectively; and the pooled estimates of 1-, 2-, 3-, 5-, and 10-year NRM were 0.16, 0.21, 0.16, 0.20, and 0.15, respectively. In the NDMM/upfront setting, the pooled estimate CR rate was 0.54, and those for 5-year OS, PFS, and NRM were 0.69, 0.40, and 0.11, respectively. In a relapsed setting, the pooled estimate CR rate was 0.31, and those for 5-year OS, PFS, and NRM were 0.24, 0.10, and 0.15, respectively. Discussion: Our results showed constant OS, PFS, and NRM from the third year onwards till the 10th year, suggesting that alloSCT has sustained survival benefits. Good response rate and promising survival outcome were observed in the NDMM/ frontline setting. Conclusion: Although comparing with other treatments, alloSCT had a lower response rate and poorer short-term survival outcome, long-term follow-up could reveal survival benefits of alloSCT in MM patients.

Stratifying osteosarcoma patients using an epigenetic modification-related prognostic signature: implications for immunotherapy and chemotherapy selection.

Background: Osteosarcoma (OS) poses significant challenges in treatment and lacks reliable prognostic markers. Epigenetic alterations play a crucial role in disease progression. This study aimed to develop an accurate prognostic signature for OS using epigenetic modification genes (EMGs). Methods: The Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-OS cohort was analyzed. Univariate Cox analysis identified survival-associated EMGs. Based on least absolute shrinkage and selection operator (LASSO) regression and multivariate analysis, a 6-gene prognostic signature termed the epigenetic modification-related prognostic signature (EMRPS) was derived in the testing cohort. Kaplan-Meier and receiver operating characteristic (ROC) curve analysis confirmed predictive accuracy through internal and external validation (GEO accession GSE21257). A prognostic nomogram incorporating EMRPS and clinical features was constructed. Transcriptomic analysis including differential gene expression, Gene Ontology (GO), gene set enrichment analysis (GSEA), and immune infiltration analysis was conducted to explore mechanisms linking EMRPS to OS prognosis. Additionally, EMRPS impact on drug sensitivity was predicted. Results: A 6-gene EMRPS comprising DDX24, DNAJC1, HDAC4, SIRT7, SP140 and UHRF2 was successfully developed. The high-risk group showed significantly shorter survival, consistently observed in both internal and external validation. EMRPS demonstrated high predictive efficacy for 1-, 3-, and 5-year overall survival, with area under curve (AUC) >0.85 in training and ~0.7 in testing. The nomogram integrating age, gender, metastasis status, and EMRPS exhibited high predictive performance based on concordance index analysis. Mechanistic analysis indicated the low-risk group had increased immune infiltration and activity with higher immune checkpoint expression, reflecting an immune-activated tumor microenvironment (TME) suitable for immunotherapy. Drug sensitivity analysis revealed the low-risk group had increased sensitivity to cisplatin, a first-line OS chemotherapy. Conclusions: Our study successfully established an efficient EMRPS and nomogram, highlighting their potential as novel prognostic markers and indicators for selecting appropriate immunotherapy and chemotherapy candidates in OS treatment.

The molecular prognostic score, a classifier for risk stratification of high-grade serous ovarian cancer.

BACKGROUND: The clinicopathological parameters such as residual tumor, grade, the International Federation of Gynecology and Obstetrics (FIGO) score are often used to predict the survival of ovarian cancer patients, but the 5-year survival of high grade serous ovarian cancer (HGSOC) still remains around 30%. Hence, the relentless pursuit of enhanced prognostic tools for HGSOC, this study introduces an unprecedented gene expression-based molecular prognostic score (mPS). Derived from a novel 20-gene signature through Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression, the mPS stands out for its predictive prowess. RESULTS: Validation across diverse datasets, including training and test sets (n = 491 each) and a large HGSOC patient cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium (n = 7542), consistently shows an area-under-curve (AUC) around 0.7 for predicting 5-year overall survival. The mPS's impact on prognosis resonates profoundly, yielding an adjusted hazard-ratio (HR) of 6.1 (95% CI: 3.65-10.3; p < 0.001), overshadowing conventional parameters-FIGO score, residual disease, and age. Molecular insights gleaned from mPS stratification uncover intriguing pathways, with focal-adhesion, Wnt, and Notch signaling upregulated, and antigen processing and presentation downregulated (p < 0.001) in high-risk HGSOC cohorts. CONCLUSION: Positioned as a robust prognostic marker, the 20-gene signature-derived mPS emerges as a potential game-changer in clinical settings. Beyond its role in predicting overall survival, its implications extend to guiding alternative therapies, especially targeting Wnt/Notch signaling pathways and immune evasion-a promising avenue for improving outcomes in high-risk HGSOC patients.

Arthroscopic Resection of Symptomatic Ossicles of the Medial Malleolus Combined With Deltoid Ligament Repairs in Athletes: A Report of Three Cases.

We report three cases of young athletes with symptomatic ossicles of the medial malleolus who underwent arthroscopic resections of the ossicle combined with deltoid ligament repair. A differential diagnosis of the ossicles beneath the medial malleolus, accessory ossification center, avulsion fracture resulting in pseudoarthrosis, and accessory bone such as os subtibiale has been proposed. However, it is difficult to differentiate them clearly. Most of these ossicles are asymptomatic, although they can cause chronic medial ankle pain, especially in young athletes who require surgical treatment. All three patients had pain in the distal part of the medial malleolus, which restricted their sports activities. Plain radiographs of all three cases revealed a well-defined, round-shaped bony lesion beneath the medial malleolus. Ultrasonographic imaging, magnetic resonance imaging, and arthroscopic findings revealed that ligament attachment to the ossicle varies in volume and type according to the cases. In other words, the mechanisms through which the existence of the ossicles affects the stability of the ankle joint and foot alignment are different in each case, indicating that deltoid ligament repair is necessary according to the cases. In all three cases, we performed arthroscopic resections of ossicles combined with deltoid ligament repairs, achieving favorable short-term clinical outcomes.

Real-world efficacy of low dose osimertinib as second-line treatment in patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer.

Background: Response rates of epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) to lower doses of osimertinib [20 mg once daily (OD) and 40 mg OD] are similar to those of the recommended dose of 80 mg OD, but there is a lack of real-world evidence on the effect of the lower doses of osimertinib on survival outcomes. We conducted this study to assess the efficacy and safety of lower osimertinib doses for patients with EGFR-mutated advanced NSCLC whose disease had progressed on earlier generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world clinical practice. Methods: This multicenter, retrospective study included patients with EGFR-mutated advanced NSCLC treated with low doses of osimertinib after failing first- or second-generation EGFR TKIs due to acquired T790M mutation. Data on demographics, staging, treatment history, best overall response rate (ORR) based on RECIST 1.1, and adverse events (AEs) were collected from the patients' case notes. Descriptive data were described in percentages and medians. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Of the 22 patients studied [males =8 and females =14; Eastern Cooperative Oncology Group (ECOG) 1 or 2 =7 and ECOG 3 or 4 =15], 45.5% were on 40 mg OD, 31.8% were on 80 mg every other day (EOD), and 22.7% on 40 mg EOD. First-line EGFR TKIs used included afatinib, erlotinib, and gefitinib. The ORR with lower doses of second-line osimertinib was 77.3%. Overall, the median PFS was 10.0 months [95% confidence interval (CI): 8.6-11.4] and median OS was 13.0 months (95% CI: 9.4-16.6). In patients with ECOG 1 or 2, the median PFS was 18.0 months (95% CI: 5.8-30.2) and the median OS was not reached at the time of analysis. In patients with poor ECOG performance status of 3 and 4, good survival outcomes were also seen with a median PFS of 7.0 months (95% CI: 4.7-9.3) and median OS of 10.0 months (95% CI: 7.5-12.5). All AEs except one case of paronychia were Grade 1. There were no Grade 3 or 4 AEs. Conclusions: Treatment with low dose osimertinib demonstrated good efficacy and tolerability in EGFR-mutated advanced NSCLC patients who failed first-line treatment with first- or second-generation EGFR TKIs due to T790M mutation.

Metabolic factors are not the direct mediators of the association between type 2 diabetes and osteoporosis.

Objective: The causal relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OS) remains unclear. This study aims to investigate the causal relationship and explore the potential metabolic mechanism and its mediating role. Methods: We conducted a comprehensive study, gathering data on 490,089 T2DM patients from the genome-wide association study (GWAS) database and selecting OS data from FinnGen and MRC-IEU sources, including 212,778 and 463,010 patients, respectively, for causal analysis. Simultaneously, we explored the potential roles of three obesity traits and 30 metabolic and inflammation-related mediating variables in the causal relationship. Results: There is a strong causal relationship between T2DM and OS. The data from our two different database sources appeared in the same direction, but after correcting for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR), the direction became the same. T2DM may increase the risk of OS [odds ratio (OR) > 1.5, p < 0.001]. Steiger's test results show that there is no reverse causality. No risk factors related to glycolipid metabolism, amino acid metabolism, and inflammation were found to mediate the causal relationship. Conclusion: This study's findings indicate a robust causal relationship between T2DM and OS, influenced by relevant factors such as BMI. Our results shed light on the pathogenesis of OS and underscore the importance for clinicians to treat metabolic disorders to prevent osteoporosis.