Adolescent idiopathic scoliosis in adulthood.

Adolescent idiopathic scoliosis (AIS) is an abnormal coronal curvature of the spine that most commonly presents in adolescence. While it may be asymptomatic, AIS can cause pain, cosmetic deformity, and physical and psychological disability with curve progression. As adolescents with AIS enter adulthood, condition outcomes vary with some experiencing curve stabilization and others noting further curve progression, chronic pain, osteoporosis/fractures, declines in pulmonary and functional capacity, among others. Regular monitoring and individualized management by healthcare professionals are crucial to address the diverse challenges and provide appropriate support for a fulfilling adult life with AIS. This review examines the prevalence, risk factors, presenting symptoms, diagnosis, management, and complications of AIS in the adult population, informing targeted interventions by clinicians caring for adult patients with AIS.

Generative AI unlocks PET insights: brain amyloid dynamics and quantification.

Introduction: Studying the spatiotemporal patterns of amyloid accumulation in the brain over time is crucial in understanding Alzheimer's disease (AD). Positron Emission Tomography (PET) imaging plays a pivotal role because it allows for the visualization and quantification of abnormal amyloid beta (Aß) load in the living brain, providing a powerful tool for tracking disease progression and evaluating the efficacy of anti-amyloid therapies. Generative artificial intelligence (AI) can learn complex data distributions and generate realistic synthetic images. In this study, we demonstrate for the first time the potential of Generative Adversarial Networks (GANs) to build a low-dimensional representation space that effectively describes brain amyloid load and its dynamics. Methods: Using a cohort of 1,259 subjects with AV45 PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we develop a 3D GAN model to project images into a latent representation space and generate back synthetic images. Then, we build a progression model on the representation space based on non-parametric ordinary differential equations to study brain amyloid evolution. Results: We found that global SUVR can be accurately predicted with a linear regression model only from the latent representation space (RMSE = 0.08 ± 0.01). We generated synthetic PET trajectories and illustrated predicted Aß change in four years compared with actual progression. Discussion: Generative AI can generate rich representations for statistical prediction and progression modeling and simulate evolution in synthetic patients, providing an invaluable tool for understanding AD, assisting in diagnosis, and designing clinical trials. The aim of this study was to illustrate the huge potential that generative AI has in brain amyloid imaging and to encourage its advancement by providing use cases and ideas for future research tracks.

Long noncoding RNA VPS9D1-AS1 promotes the progression of endometrial cancer via regulation of the miR-187-3p/S100A4 axis.

VPS9D1-AS1 functions as an oncogene in many cancers. However, its role and potential mechanism in the progression of endometrial cancer (EC) are not fully understood. VPS9D1-AS1 levels in EC and adjacent normal tissues were investigated using the TCGA-UCEC cohort and 24 paired clinical samples. The roles of VPS9D1-AS1 and miR-187-3p in cell cycle, proliferation, and apoptosis were evaluated by loss- and gain-of-function experiments. In addition, the effect of VPS9D1-AS1 on tumor growth was further investigated in vivo. Rescue experiments were performed to investigate the involvement of the miR-187-3p/S100A4 axis in VPS9D1-AS1 knockdown-mediated antitumor effects. VPS9D1-AS1 was highly expressed in EC tissues. VPS9D1-AS1 knockdown, similar to miR-187-3p overexpression, significantly inhibited cell proliferation, inhibited colony formation, induced cell cycle arrest, and facilitated apoptosis of KLE cells. MiR-187-3p bound directly to VPS9D1-AS1 and the 3'UTR of S100A4. Furthermore, VPS9D1-AS1 negatively regulated miR-187-3p while positively regulating S100A4 expression in EC cells. MiR-187-3p knockdown or S100A4 overexpression partially reversed the tumor suppressive function of VPS9D1-AS1 knockdown. The results suggest that VPS9D1-AS1 affects EC progression by regulating the miR-187-3p/S100A4 axis. This may provide a promising therapeutic target to help treat EC.

Lenvatinib radiofrequency ablation sequential therapy offers survival benefits for patients with unresectable hepatocellular carcinoma at intermediate stage and the liver reserve of Child-Pugh A category: A multicenter study.

AIM: This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients. METHODS: One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child-Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib. The study compared overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) between patients undergoing sequential therapy and lenvatinib monotherapy. RESULTS: After propensity score matching, 25 patients on sequential therapy and 50 on monotherapy were evaluated. Independent factors influencing OS were identified as sequential therapy, modified albumin-bilirubin (mALBI) grade, and relative dose intensity (%) with hazard ratios (HRs) of 0.381 (95% confidence interval [CI], 0.186-0.782), 2.220 (95% CI, 1.410-3.493), and 0.982 (95% CI, 0.966-0.999), respectively. Stratified analysis based on mALBI grades confirmed the independent influence of treatment strategy across all mALBI grades for OS (HR, 0.376; 95% CI, 0.176-0.804). Furthermore, sequential therapy was identified as an independent factor of PFS (HR, 0.382; 95% CI, 0.215-0.678). Sequential therapy significantly outperformed monotherapy on survival benefits (OS: 38.27 vs. 18.96 months for sequential therapy and monotherapy, respectively, p = 0.004; PFS: 13.80 vs. 5.32 months for sequential therapy and monotherapy, respectively, p < 0.001). Sequential therapy was significantly associated with complete response by modified Response Evaluation Criteria in Solid Tumors (odds ratio, 63.089). Ten of 119 patients experienced grade 3 AEs, with no AE beyond grade 3 observed. CONCLUSION: Lenvatinib RFA sequential therapy might offer favorable tolerability and potential prognostic improvement compared to lenvatinib monotherapy.

Risk factors for chronic kidney disease progression over 20 years for primary prevention in Japanese individuals at a preventive medicine research center: Focus on the influence of plasma glucose levels.

AIMS/INTRODUCTION: Chronic kidney disease (CKD) is a very important issue globally because of the risk of its progressing to end-stage renal disease. We aimed to identify factors contributing to long-term estimated glomerular filtration rate (eGFR) decline to determine an early diagnosis and prevent CKD progression. MATERIALS AND METHODS: From January 2003 to December 2006, 5,507 individuals underwent health checkups at our hospital's Preventive Medicine Research Center. We ultimately enrolled 2,175 individuals. The eGFR was ≥60 mL/min/1.73 m2 at the start of observation period, which was 20 years. The event onset time was the day that the eGFR became <30 mL/min during the 20-year period. Baseline risk factors - in particular, the effect of plasma glucose levels on the eGFR - were extracted and evaluated by using Fine and Gray analysis. RESULTS: During the 20-year observation, the hazard ratio (HR) of CKD progression was examined. A fasting plasma glucose (FPG) level ≥105 mg/dL was significantly associated with the risk of CKD progressing to an eGFR <30 mL/min. This trend was similar in the slope of eGFR. An FPG ≥105 mg/dL or an glycated hemoglobin level ≥6.5% was useful for intervening in CKD progression. Multivariate analysis showed that independent risk factors were an FPG level ≥105 mg/dL (HR 1.9; P < 0.001), age ≥60 years (HR 3.86; P < 0.001), obesity (HR 1.61; P < 0.01) and urinary protein (HR 1.55; P < 0.01). CONCLUSIONS: For early intervention against a reduction in the eGFR, detecting mild increases in FPG ≥105 mg/dL in patients with CKD with or without diabetes is useful.

Role of cell division cycle-associated proteins in regulating cell cycle and promoting tumor progression.

The cell division cycle-associated protein (CDCA) family is important in regulating cell division. High CDCA expression is significantly linked to tumor development. This review summarizes clinical and basic studies on CDCAs conducted in recent decades. Furthermore, it systematically introduces the molecular expression and function, key mechanisms, cell cycle regulation, and roles of CDCAs in tumor development, cell proliferation, drug resistance, invasion, and metastasis. Additionally, it presents the latest research on tumor diagnosis, prognosis, and treatment targeting CDCAs. These findings are pivotal for further in-depth studies on the role of CDCAs in promoting tumor development and provide theoretical support for their application as new anti-tumor targets.

Comparative efficacy of Bacillus Calmette-Guérin instillation and radical cystectomy treatments for high-risk non-muscle-invasive urothelial cancer classified as high-grade T1 in initial and repeat transurethral resection of bladder tumor.

Objective: To compare the differential therapeutic effects of Bacillus Calmette-Guérin (BCG) instillation and radical cystectomy (RC) for high-risk non-muscle-invasive urothelial cancer (NMIBC) classified as high-grade T1 in initial and repeat transurethral resection of bladder tumors (TURBT) and to construct a prediction model. Methods: We retrospectively analyzed the clinical data of patients with malignant bladder tumors treated at the First Affiliated Hospital of Soochow University from January 2016 to December 2017 and compared the differences in 1-year, 2-year, 3-year, 5-year, and comprehensive overall survival (OS) and progression-free survival (PFS) between BCG instillation treatment and RC treatment. Survival curves were drawn to show differences in OS and PFS between the two groups. Concurrently, univariate and multivariate COX analyses were performed to identify risk factors affecting OS and PFS, and a nomogram was created. Results: In total, 146 patients were included in the study, of whom 97 and 49 were in the BCG and RC groups, respectively. No statistical differences were observed in the 1- and 2-year OS and PFS between the two groups, whereas significant statistical differences were found in the 3-year, 5-year, and comprehensive OS and PFS. Survival curves also confirmed the statistical differences in OS and PFS between the BCG and RC groups. Multivariate COX analysis revealed that the treatment method, concomitant satellite lesions, and albumin-to-alkaline phosphatase ratio (AAPR) were independent risk factors affecting OS and PFS. The nomogram that was further plotted showed good predictive ability for OS and PFS. Conclusion: For patients who exhibit high-level T1 pathology after both initial and repeat TURBT, especially those with low AAPR, and concomitant satellite lesions, choosing RC as a treatment method offers a better prognosis.

Overexpression of circular RNA hsa_circ_0008621 facilitates colorectal cancer progression and predicts poor prognosis.

Aim: To evaluate the potential role of serum and tissue hsa_circ_0008621 as a prognostic biomarker for CRC patients. Focused on the functional role of hsa_circ_0008621 in colorectal cancer (CRC). Methods: Serum and tissue hsa_circ_0008621 expression were quantified by qRT-PCR in 157 CRC patients, as well as 100 serums from healthy controls. Serum and tissue hsa_circ_0008621 expression was evaluated for their prognostic role in CRC patients using Kaplan-Meier curves and Multivariate Cox proportional hazards analysis. To further characterize the biological role of hsa_circ_0008621 expression in CRC, in vitro hsa_circ_0008621 inhibition was performed and the effects on cellular growth, migration, invasion, apoptosis, and glycolysis were explored. Next, the downstream molecules for hsa_circ_0008621 were predicted. Results: Hsa_circ_0008621 expression was significantly upregulated in CRC tissues and serums. Serum hsa_circ_0008621 levels were significantly up-regulated in advanced-staged samples. High serum hsa_circ_0008621 expression was associated with shorter overall survival and recurrence-free survival in CRC patients. Multivariate Cox regression analysis identified a high level of serum hsa_circ_0008621 expression as an independent prognostic factor with respect to overall survival and recurrence-free survival. Loss of function assays for hsa_circ_0008621 in vitro led to a significant decrease in cell proliferation, migration, invasion, and glycolysis, but an increase in cell apoptosis. Hsa_circ_0008621 can sponge miR-532-5p, which targets SLC16A3. Conclusion: High level of serum hsa_circ_0008621 is associated with poor survival in CRC and promotes CRC progression, suggesting it to be a promising non-invasive prognostic biomarker and novel therapeutic target in CRC patients.

Capivasertib in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative advanced breast cancer.

PURPOSE: This review discusses the role and efficacy of Capivasertib in managing Hormone Receptor-Positive (HR+) breast cancer. SUMMARY: Breast cancer is the most prevalent type of cancer among women worldwide. This article is an in-depth analysis of advanced therapeutic options involving Capivasertib in treating HR+ Breast Cancer. It focuses on the mode of action, efficacy, clinical trials, and comparison with fulvestrant alone. This review also highlights the therapy's precision in targeting specific cancer cells. Its mechanism of action involves preventing cancer cells from growing and having a cytotoxic effect on them. It improves progression-free survival while maintaining the quality of life. The side effects can be easily managed by dose reduction or discontinuation of the drug. This article sheds light on the ongoing trials and FDA recognition. CONCLUSION: In conclusion, Capivasertib-fulvestrant therapy shows potential as an innovative therapeutic option for HR+ breast cancer but warrants additional research, especially in randomized control trials (RCT). It resulted in longer progression-free survival compared to fulvestrant alone. Its side effect profile is minimal.

Impact of sex on clinical outcome in early Multiple Sclerosis.

BACKGROUND: Previous evidence suggests sex differences in the clinical course of relapsing remitting multiple sclerosis (RRMS), but comprehensive early-stage prospective studies are lacking. We aim to quantify the impact of sex on clinical outcomes in early-stage RRMS. METHODS: Utilizing prospective cohort data, we assessed the impact of biological sex on time-to-relapse, disability progression (Expanded Disability Status Scale [EDSS]), extremity function (Nine-Hole Peg Test, Timed-25-food walk test), cognition (Paced Auditory Serial Addition Test, Symbol Digit Modalities Test), quality-of-life (Hamburg Quality of Life Questionnaire in Multiple Sclerosis, Short-Form-36), fatigue (Fatigue Severity Scale, Fatigue Scale for Motor and Cognitive functions), and depression (Beck Depression Inventory-II) in clinically isolated syndrome (CIS) or RRMS patients. Inclusion was within 12 months of symptom onset. Linear, negative binomial, mixed, and Cox models estimated male vs. female effects at the four-year follow-up including baseline-to-follow-up course. RESULTS: We included 149 patients (65.1 % female). Eighty-five completed four-year follow-up. No sex differences in time-to-relapse emerged (HR = 0.91;95 %CI = 0.53-1.58). Males had no increased risk of EDSS worsening (OR = 0.75;95 %CI = 0.21-2.35) compared to females. Similarly, minor/no sex differences emerged in other outcomes. CONCLUSIONS: Four years after first manifestation, neither disease activity (disability progression and relapse rate) nor patient-reported outcomes showed sex-related disparities in this early-MS-cohort. GOV IDENTIFIER: NCT01371071.

Fbxo28 is essential for spindle migration and morphology during mouse oocyte meiosis I.

Spindle migration and assembly regulates asymmetric oocyte division, which is essential for fertility. Fbxo28, as a member of SCF (Skp1-Cul1-F-box) ubiquitin E3 ligases complex, is specifically expressed in oocytes. However, little is known about the functions of Fbxo28 in spindle assembly and migration during oocyte meiosis I. In present study, microinjection with morpholino oligonucleotides and exogenous mRNA for knockdown and rescue experiments, and immunofluorescence staining, western blot, timelapse confocal microscopy and chromosome spreading were utilized to explore the roles of Fbxo28 in asymmetric division during meiotic maturation. Our data suggested that Fbxo28 mainly localized at chromosomes and acentriolar microtubule-organizing centers (aMTOCs). Depletion of Fbxo28 did not affect polar body extrusion but caused defects in spindle morphology and migration, indicative of the failure of asymmetric division. Moreover, absence of Fbxo28 disrupted both cortical and cytoplasmic actin assembly and decreased the expression of ARPC2 and ARP3. These defects could be rescued by exogenous Fbxo28-myc mRNA supplement. Collectively, this study demonstrated that Fbxo28 affects spindle morphology and actin-based spindle migration during mouse oocyte meiotic maturation.

Remnant cholesterol is associated with the progression and regression of metabolic dysfunction-associated steatotic liver disease in Chinese adults.

BACKGROUND: The aim of this study was to explore the associations of serum remnant cholesterol (RC) levels with the progression and regression of metabolic dysfunction-associated steatotic liver disease (MASLD) in Chinese adults. METHODS: We conducted a cross-sectional study in 13,903 individuals who underwent transient elastography tests (cohort 1) and a longitudinal study in 17,752 individuals who underwent at least two health check-up exams with abdominal ultrasound (cohort 2). Anthropometric and biochemical parameters were collected. Serum RC levels were calculated. Noninvasive fibrosis indices such as FIB-4 were evaluated in cohort 2. RESULTS: In cohort 1, serum RC levels were positively and independently associated with the severity of hepatic steatosis and liver fibrosis according to logistic regression analysis. In cohort 2, baseline serum RC levels were increased in participants with the incidence of MASLD and decreased in participants with the regression of MASLD during the follow-up period. Baseline serum RC levels were independently associated with an increased risk of development and a decreased likelihood of regression of MASLD: the fully adjusted hazard ratios (HR) were 2.785 (95 % CI 2.332-3.236, P < 0.001) and 2.925 (95 % CI 2.361-3.623, P < 0.001), respectively. In addition, when we used FIB-4 to evaluate liver fibrosis, baseline serum RC levels were positively correlated with the incidence of high-intermediate probability of advanced fibrosis. However, we did not find an association between serum RC levels and the regression of liver fibrosis. CONCLUSION: Serum RC levels are independently correlated with the progression and regression of MASLD in Chinese adults, suggesting that RC may participate in the pathophysiological process of MASLD.

Label-Free Monitoring of Endometrial Cancer Progression Using Multiphoton Microscopy.

Endometrial cancer is the most common gynecological cancer in the developed world. However, the accuracy of current diagnostic methods is still unsatisfactory and time-consuming. Here, we presented an alternate approach to monitoring the progression of endometrial cancer via multiphoton microscopy imaging and analysis of collagen, which is often overlooked in current endometrial cancer diagnosis protocols but can offer a crucial signature in cancer biology. Multiphoton microscopy (MPM) based on the second-harmonic generation and two-photon excited fluorescence was introduced to visualize the microenvironment of endometrium in normal, hyperplasia without atypia, atypical hyperplasia, and endometrial cancer specimens. Furthermore, automatic image analysis based on the MPM image processing algorithm was used to quantify the differences in the collagen morphological features among them. MPM enables the visualization of the morphological details and alterations of the glands in the development process of endometrial cancer, including irregular changes in the structure of the gland, increased ratio of the gland to the interstitium, and atypical changes in the glandular epithelial cells. Moreover, the destructed basement membrane caused by gland proliferation and fusion is clearly shown in SHG images, which is a key feature for identifying endometrial cancer progression. Quantitative analysis reveals that the formation of endometrial cancer is accompanied by an increase in collagen fiber length and width, a progressive linearization and loosening of interstitial collagen, and a more random arrangement of interstitial collagen. Observation and quantitative analysis of interstitial collagen provide invaluable information in monitoring the progression of endometrial cancer. Label-free multiphoton imaging reported here has the potential to become an in situ histological tool for effective and accurate early diagnosis and detection of malignant lesions in endometrial cancer.

Hepatic arterial infusion chemotherapy plus camrelizumab and apatinib for advanced hepatocellular carcinoma.

BACKGROUND AND AIMS: There is limited information on combination of hepatic arterial infusion chemotherapy (HAIC) and systemic therapy for advanced hepatocellular carcinoma (Ad-HCC). We aim to compare the efficacy and safety of HAIC plus camrelizumab (a PD-1 inhibitor) and apatinib (an VEGFR-2 inhibitor) versus camrelizumab and apatinib for Ad-HCC. METHODS: From April 2019 to October 2022, 416 patients with Ad-HCC who received either HAIC plus camrelizumab and apatinib (TRIPLET protocol, n = 207) or camrelizumab and apatinib (C-A protocol, n = 209) were reviewed retrospectively. The propensity score matching (PSM) was used to reduce selective bias. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan-Meier method with the log-rank test. Cox regression analyses of independent prognostic factors were evaluated. RESULTS: After PSM 1:1, 109 patients were assigned to two groups. The median OS of not reached in the TRIPLET group was significantly longer than that of 19.9 months in the C-A group (p < 0.001), while in the TRIPLET group, the median PFS of 11.5 months was significantly longer than that of 9.6 months in the C-A group (p < 0.001). Multivariate analyses showed that the factors significantly affected the OS were CTP grade, tumor number > 3, and TRIPLET treatment (p < 0.001). Grade 3/4 adverse events occurred at a rate of 82.1% vs. 71.3% in TRIPLET and C-A groups, respectively. CONCLUSION: The TRIPLET protocol has promising survival benefits in the management of patients with Ad-HCC, with acceptable safety. TRAIL REGISTRATION: The study has been retrospectively registered at Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ , ChiCTR2300075828).

Radiomics score derived from T1-w/T2-w ratio image can predict motor symptom progression in Parkinson's disease.

OBJECTIVES: To clarify the association between a radiomics score (Rad-score) derived from T1-weighted signal intensity to T2-weighted signal intensity (T1-w/T2-w) ratio images and the progression of motor symptoms in Parkinson's disease (PD). MATERIALS AND METHODS: This retrospective study included patients with PD enrolled in the Parkinson's Progression Markers Initiative. The Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part III score ≥ 33 and/or Hoehn and Yahr stage ≥ 3 indicated motor function decline. The Rad-score was constructed using radiomics features extracted from T1-w/T2-w ratio images. The Kaplan-Meier analysis and Cox regression analyses were used to assess the time differences in motor function decline between the high and low Rad-score groups. RESULTS: A total of 171 patients with PD were divided into training (n = 101, mean age at baseline, 61.6 ± 9.3 years) and testing (n = 70, mean age at baseline, 61.6 ± 10 years). The patients in the high Rad-score group had a shorter time to motor function decline than those in the low Rad-score group in the training dataset (log-rank test, p < 0.001) and testing dataset (log-rank test, p < 0.001). The multivariate Cox regression using the Rad-score and clinical factors revealed a significant association between the Rad-score and motor function decline in the training dataset (HR = 2.368, 95%CI:1.423-3.943, p < 0.001) and testing dataset (HR = 2.931, 95%CI:1.472-5.837, p = 0.002). CONCLUSION: Rad-scores based on radiomics features derived from T1-w/T2-w ratio images were associated with the progression of motor symptoms in PD. CLINICAL RELEVANCE STATEMENT: The radiomics score derived from the T1-weighted/T2-weighted ratio images offers a predictive tool for assessing the progression of motor symptom in patients with PD. KEY POINTS: Radiomics score derived from T1-weighted/T2-weighted ratio images is correlated with the motor symptoms of Parkinson's disease. A high radiomics score correlated with faster motor function decline in patients with Parkinson's disease. The proposed radiomics score offers predictive insight into the progression of motor symptoms of Parkinson's disease.

Knockdown of hsa_circ_0102231 Impedes the Progression of Liver Cancer through the miR-873-SOX4 Axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. AIM: The objective of this study was to investigate the role of circular RNA 0102231 (hsa_circ_ 0102231) in the progression of liver cancer. METHODS: In this study, quantitative polymerase chain reaction experiments were performed to quantify the hsa_circ_0102231 level in different liver cancer cell lines. Bioinformatics analysis, as well as a dual-luciferase reporter and RNA pull-down assay, were used to identify putative hsa_circ_ 0102231 downstream targets. Colony formation and CCK8 assays were utilized to examine cell proliferation, whereas Transwell assays were employed to monitor cell migration. Lastly, the role of hsa_circ_0102231 in liver cancer was assessed in a subcutaneous xenograft model. RESULTS: The expression of hsa_circ_0102231 increased significantly in HepG2 and Huh-7 cells compared with controls, and hsa_circ_0102231 knockdown inhibited cell proliferation and migration in vitro and in vivo. Bioinformatics analysis, as well as a dual-luciferase reporter and RNA pulldown assay, revealed that miR-873 and SOX4 were hsa_circ_0102231 downstream targets. miR-873 inhibition or SOX4 overexpression rescued the proliferation and migration of HepG2 and Huh-7 cells after hsa_circ_0102231 knockdown. Furthermore, SOX4 overexpression reversed the miR-873-induced inhibition of cell migration and proliferation in vitro. CONCLUSION: These results show that hsa_circ_0102231 knockdown impedes the progression of liver cancer by regulating the miR-873/SOX4 axis. However, further studies are needed to determine whether hsa_circ_0102231 may be a therapeutic target in liver cancer.

Multi-omics analysis reveals drivers of loss of ß-cell function after newly diagnosed autoimmune type 1 diabetes: An INNODIA multicenter study.

AIMS: Heterogeneity in the rate of ß-cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease-modifying clinical trials. Integrative analyses of baseline multi-omics data obtained after the diagnosis of type 1 diabetes may provide mechanistic insight into the diverse rates of disease progression after type 1 diabetes diagnosis. METHODS: We collected samples in a pan-European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients. In this study, we used Multi-Omics Factor Analysis to identify molecular signatures correlating with post-diagnosis decline in ß-cell mass measured as fasting C-peptide. RESULTS: Two molecular signatures were significantly correlated with fasting C-peptide levels. One signature showed a correlation to neutrophil degranulation, cytokine signalling, lymphoid and non-lymphoid cell interactions and G-protein coupled receptor signalling events that were inversely associated with a rapid decline in ß-cell function. The second signature was related to translation and viral infection was inversely associated with change in ß-cell function. In addition, the immunomics data revealed a Natural Killer cell signature associated with rapid ß-cell decline. CONCLUSIONS: Features that differ between individuals with slow and rapid decline in ß-cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies as well as offering biomarkers of therapeutic effect.

Research on the mechanism of TWSG1 in the malignant progression of glioma cells and tumor-associated macrophage infiltration.

Gliomas are malignant tumors of the central nervous system; current treatment methods have low efficacy. Twisted gastrulation BMP signaling modulator 1 (TWSG1) has been shown to play a role in gliomas but it is not known whether TWSG1 participates in glioma pathogenesis and macrophage immune regulation. This study identified a total of 24 differentially expressed genes with survival differences in gliomas using bioinformatics analysis. Among them, TWSG1 exhibited the strongest correlation with gliomas and was positively correlated with macrophage enrichment. The results showed that TWSG1 was highly expressed in various glioma cell lines, with the highest expression observed in the A172 cell line. Silencing TWSG1 significantly decreased the viability, migration, and invasion of A172 cells in vitro and tumor growth in a mouse xenograft model in vivo. It also reduced the expression of the matrix metalloproteinases MMP2 and MMP9 both in vivo and in vitro. Silencing TWSG1 significantly reduced the expression of M2 macrophage makers and upregulated the expression of M1 macrophage markers in A172 cells and tumor tissues. These data suggest that interference with TWSG1 suppressed the progression of A172 glioma cells and regulated immune infiltration.

JARID2, a novel regulatory factor, promotes cell proliferation, migration, and invasion in oral squamous cell carcinoma.

BACKGROUND: Accurate regulation of gene expression is crucial for normal development and function of cells. The prognostic significance and potential carcinogenic mechanisms of the related gene JARID2 in OSCC are not yet clear, but existing research has indicated a significant association between the two. METHODS AND MATERIALS: The relationship between the expression of the JARID2 gene in tumor samples of OSCC patients and clinical pathological factors was analyzed using immunohistochemistry experiments and RT-qPCR analysis. Based on the clinical pathological data of patients, bioinformatics analysis was conducted using public databases to determine the function of JARID2 in OSCC. Knockdown OSCC cell lines were constructed, and the impact of JARID2 on the biological behavior of OSCC cell lines was assessed through CCK-8, wound healing assay, and transwell analysis. RESULTS: Immunohistochemistry experiments confirmed the correlation between JARID2 and the prognosis of OSCC patients, while RT-qPCR experiments demonstrated its expression levels in tissue and cells. CKK-8 experiments, wound healing assays, and Transwell experiments indicated that knocking down JARID2 had a negative impact on the proliferation, invasion, and migration of OSCC cells. Bioinformatics analysis results showed that the expression of JARID2 in OSCC is closely associated with patient gene co-expression, gene function enrichment, immune infiltration, and drug sensitivity. CONCLUSION: Our study indicates that JARID2 is a novel prognostic biomarker and potential therapeutic target for OSCC.

Chemotherapy related changes in cfDNA levels in squamous non-small cell lung cancer: correlation with symptom scores and radiological responses.

Aim: There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses. Methods: Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (n = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); n = 27] and healthy-controls (n = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy. Results: At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days vs. 298 days and median PFS = 97 days vs. 197 days; P = 0.025; hazard ratio (HR) = 2.17]. Conclusions: Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.