Anti-peptide antibodies, anti-SNRK and anti-HUWE1 antibodies, as potential predictors of good response to tofacitinib therapy in rheumatoid arthritis patients.

OBJECTIVES: To maximize the cost-effectiveness of tofacitinib, one of Janus kinase inhibitors, there is an unmet need to identify predictors of therapeutic response. Utilizing phage immunoprecipitation sequencing (PhIP-Seq), we aim to identify peptide biomarkers for predicting good response to tofacitinib in rheumatoid arthritis (RA) patients. METHODS: We enrolled 106 patients who had received 24-week tofacitinib therapy, including twelve patients undergoing PhIP-Seq analysis in the discovery stage and ninety-four patients validated with enzyme-linked immunosorbent assay (ELISA) in the replication stage. Disease activity was assessed using the 28-joint disease activity score-erythrocyte sedimentation rate, and therapeutic response was evaluated using EULAR response criteria. Plasma levels of caspase-1 and IL-18 were determined using ELISA. RESULTS: PhIP-Seq analysis identified antibodies to sucrose non-fermenting-related kinase (SNRK) and HUWE1 (ubiquitin E3 ligase) as peptide biomarkers for discriminating good responders from the non-good responders. Using ELISA for validation on another cohort, an optimal cut-off value of anti-SNRK antibody for predicting good response was 0.381, with AUC 0.823, specificity 80.6%, and sensitivity 78.1% (p = 3.01E-07), and anti-HUWE1 antibody at 0.362, with AUC 0.740, specificity 74.2%, and sensitivity 62.5% (p < 0.001). Plasma levels of anti-SNRK and anti-HUWE1 antibodies were positively correlated with levels of caspase-1 and IL-18 (both p < 0.05). Multivariate logistic regression analysis revealed anti-SNRK antibody as a significant predictor of good therapeutic response. After tofacitinib therapy, anti-SNRK antibody levels significantly declined in good responders, but not in non-good responders. CONCLUSION: We identify two peptide antibodies, anti-SNRK and anti-HUWE1 antibodies, as pretreatment predictors of good therapeutic response to tofacitinib in RA patients.

A Circadian Rhythm-related Signature to Predict Prognosis, Immunei Infiltration, and Drug Response in Breast Cancer.

PURPOSE: Circadian rhythm genes (CRRGs) play essential roles in cancer occurrence and development. However, the prognostic significance of CRRGs in breast cancer (BC) has not been fully elucidated. Our study aimed to develop a prognostic gene signature based on CRRGs that can accurately and stably predict the prognosis of BC. METHODS: The transcriptome data and clinical information for BC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A consensus unsupervised clustering analysis was carried out to investigate the roles of CRRGs in BC. A CRRGs-related prognostic risk model was established by using logistic least absolute shrinkage and selection operator (LASSO) Cox regression and univariate Cox regression analyses. Kaplan-Meier (KM) curves analysis, time-dependent receptor operation characteristics (ROC) curves analysis, and nomogram were plotted to evaluate the predictive efficacy of the model. The relevance of risk score to the immune cell infiltration, tumor burden mutation (TMB), and therapeutic response was assessed. RESULTS: A risk model comprising six CRRGs (SLC44A4, SLC16A6, TPRG1, FABP7, GLYATL2, and FDCSP) was constructed and validated, demonstrating a good predictor of BC. The low-risk group displayed a higher number of immune activities and immune checkpoint expression and a lower burden of tumor mutation. Additionally, drug sensitivity analysis demonstrated the prognostic signature may serve as a potential chemosensitivity predictor. CONCLUSION: We established 6 CRRGs-related risk signatures for the prognosis of BC, which is of great value in predicting the prognosis of patients with BC and guiding the treatment for BC.

Associations between sleep disorders and clinical outcomes of patients with primary biliary cholangitis.

PURPOSE: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by a range of symptoms, including sleep disturbances. The present study aimed to investigate the prevalence of sleep disorders and the associations between sleep disorders and clinical outcomes in PBC. PATIENTS AND METHODS: We enrolled 177 patients with PBC and 165 healthy controls (age- and sex-matched). Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Demographic and clinical data were collected from comprehensive clinical records to investigate whether sleep disorder was correlated with disease severity, therapeutic response and liver cirrhosis. RESULTS: The prevalence of sleep disorders in patients with PBC (50.8 â€‹%) was significantly higher than healthy controls (18.2 â€‹%). Patients with sleep disorders presented with higher levels of laboratory parameters including globulin (GLO), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL) and immunoglobulin M (IgM), as well as higher ratio of poor therapeutic response and liver cirrhosis (p â€‹< â€‹0.05). There was a positive correlation between global PSQI score and AST, ALP, GGT, TBIL, DBIL and IgM in patients with PBC. Patients with poor therapeutic response and liver cirrhosis in PBC had a higher proportion of sleep disorders and more chaotic sleep patterns, whereas a stronger correlation between sleep quality and laboratory parameters was found in patients with liver cirrhosis. CONCLUSIONS: Sleep disorders were prevalent and manifested as adverse effects in PBC. Assessment of sleep quality and intervention were essential to the overall clinical management of patients with PBC.

Subcellular expression of CD30 in cutaneous mastocytosis-An important factor for targeted treatment.

BACKGROUND: The subcellular distribution of CD30 on mast cells and the presence of eosinophils in cutaneous mastocytosis require further investigation, especially as the cell surface expression of CD30 is critical for the therapeutic response of systemic mastocytosis to brentuximab vedotin. OBJECTIVE: Investigation of 147 biopsy specimens from 143 patients with cutaneous mastocytosis for mast cell density and distribution, frequency of CD30 expression, CD30 staining patterns, and presence and distribution of eosinophils. Correlation with clinical patterns. METHODS: Retrospective multicenter immunohistochemical study of CD30 expression, eosinophils and basic clinical data in cutaneous mastocytosis. RESULTS: CD30 expression was found in all samples (cut-off: ≥1%), whereby the staining was predominantly cytoplasmic in 99% of the samples. Additional membrane staining was detected in 62% of the samples. Surface expression of CD30 was more common in biopsy specimens with a high mast cell burden and in biopsy specimens with a higher CD30 expression rate. Eosinophils were admixed in 58% of the samples. Females and older patients showed a trend of a lower mast cell burden. LIMITATIONS: Retrospective study on formalin-fixed and paraffin-embedded tissue without functional analysis. CONCLUSION: Most cases of cutaneous mastocytosis show cell surface expression of CD30 expression and is, therefore, in principle, accessible for therapy with antibodies against CD30, provided the overall situation of the patient warrants.

Letter to the Editor: "The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma".

This letter to the editor discusses the findings of Yu et al. (2024), which highlight the prognostic significance of volumetric assessments over cross-product measurements in pediatric diffuse intrinsic pontine glioma (DIPG). The study's methodology enhances precision in monitoring therapeutic responses, offering insights into treatment adjustments based on detailed imaging features. Emphasizing the value of volumetric MRI, this letter suggests its potential to improve surgical planning and therapeutic strategies, thereby optimizing patient management. This approach could revolutionize treatment paradigms, emphasizing personalized care through advanced imaging techniques.

Characteristics in patients with very early therapeutic response of condoliase chemonucleolysis for lumbar disc herniation.

INTRODUCTION: Treatment of lumbar disc herniation (LDH) using condoliase chemonucleolysis (CC) requires more time than surgery to demonstrate therapeutic effects. This study aimed to identify patients who show significant improvement in leg pain very early after CC and to determine pretreatment factors that can predict a very early therapeutic response. METHODS: The study included 52 patients who underwent CC for treatment-resistant LDH. Scores for low back and leg pain measured by a numerical rating scale were assessed at four time points (1 day, 1 week, 1 month, and 3 months after CC). Patients who reported subjective pain relief the day after treatment and further exhibited an improved straight leg raising (SLR) angle compared to pretreatment were classified as "very early responders (VER)". RESULTS: Of the 52 patients, 39 (75%) were VER, and 13 (25%) were non-VER. The VER showed earlier improvement in leg pain. The VER had a significantly higher proportion of positive SLR test patients (p = 0.01) and a significantly smaller pretreatment SLR angle compared to the non-VER (VER vs. non-VER: 40.6 ± 19.0 vs. 63.1 ± 16.9, p < 0.001). There were no significant differences in the level, type, and size of LDH and the disc regression rate between the two groups. CONCLUSIONS: Patients with a smaller pretreatment SLR angle are more likely to experience very early or early symptomatic relief, with a significant and sustained reduction in leg pain up to 3 months after CC treatment.

Prognostic factors in children and adolescents with differentiated thyroid cancer treated with total thyroidectomy and radioiodine therapy: a retrospective two-center study from China.

Purpose: This two-center study aimed to explore the main prognostic factors affecting the final disease status in children and adolescents with differentiated thyroid cancer (caDTC) following total thyroidectomy and radioiodine therapy (RAIT). Materials and methods: All caDTC patients from two centers in the period from 2004-2022 were retrospectively included. At the last follow-up, the patients' disease status was assessed and classified as an incomplete response (IR) or as an excellent or indeterminate response (EIDR). Then, the difference in preablation stimulated thyroglobulin (ps-Tg) levels between the two groups was compared, and the threshold for predicting IR was determined using receiver operating characteristic (ROC) analysis. Moreover, univariate and multivariate analyses were conducted to identify the factors influencing the patients' ultimate disease outcomes. Results: A total of 143 patients (98 females, 45 males; median age 16 years) were recruited. After a median follow-up of 42.9 months, 80 patients (55.9%) exhibited an EIDR, whereas 63 patients (44.1%) exhibited an IR. Patients with an IR had significantly greater ps-Tg levels than did those with an EIDR (median ps-Tg 79.2 ng/mL vs. 9.3 ng/mL, p<0.001). The ROC curve showed that ps-Tg ≥20 ng/mL was the most accurate for predicting IR at the last follow-up. According to multivariate analysis, only ps-Tg, T stage and the therapeutic response to initial RAIT were significantly associated with IR. Conclusion: In caDTC patients, the ps-Tg level, T stage, and response to initial RAIT are critical final outcome indicators.

A Research Protocol for a Phase II Single-Arm Clinical Trial Assessing the Feasibility and Efficacy of Neoadjuvant Anastrozole in Patients With Luminal Breast Cancer and Low Proliferative Index: The ANNE Trial.

INTRODUCTION: Neoadjuvant endocrine therapy (NET) is recommended for the treatment of invasive breast cancer (BC), particularly luminal subtypes, in locally advanced stages. Previous randomized studies have demonstrated the benefits of aromatase inhibitors in this context. However, NET is typically reserved for elderly or frail patients who may not tolerate neoadjuvant chemotherapy. Identifying non-responsive patients early and extending treatment for responsive ones would be ideal, yet optimal strategies are awaited. AIMS: This non-randomized phase 2 clinical trial aims to assess NET feasibility and efficacy in postmenopausal stage II and III luminal BC patients, identifying predictive therapeutic response biomarkers. Efficacy will be gauged by patients with Ki67 ≤ 10% after 4 weeks and Preoperative Endocrine Prognostic Index (PEPI) scores 0 post-surgery. Study feasibility will be determined by participation acceptance rate (recruitment rate ≥50%) and inclusion rate (>2 patients/month). METHODS: Postmenopausal women with luminal, HER2-tumors in stages II and III undergo neoadjuvant anastrozole treatment, evaluating continuing NET or receiving chemotherapy through early Ki67 analysis after 2 to 4 weeks. The study assesses NET extension for up to 10 months, using serial follow-ups with standardized breast ultrasound and clinical criteria-based NET suspension. Clinical and pathological responses will be measured overall and in the luminal tumor A subgroup. Toxicity, health-related quality of life, and circulating biomarkers predicting early NET response will also be evaluated.

EMT-related gene classifications predict the prognosis, immune infiltration, and therapeutic response of osteosarcoma.

Background: Osteosarcoma (OS), a bone tumor with high ability of invasion and metastasis, has seriously affected the health of children and adolescents. Many studies have suggested a connection between OS and the epithelial-mesenchymal transition (EMT). We aimed to integrate EMT-Related genes (EMT-RGs) to predict the prognosis, immune infiltration, and therapeutic response of patients with OS. Methods: We used consensus clustering to identify potential EMT-Related OS molecular subtypes. Somatic mutation, tumor immune microenvironment, and functional enrichment analyses were performed for each subtype. We next constructed an EMT-Related risk signature and evaluated it by Kaplan-Meier (K-M) analysis survival and receiver operating characteristic (ROC) curves. Moreover, we constructed a nomogram to more accurately predict OS patients' clinical outcomes. Response effects of immunotherapy in OS patients was analyzed by Tumor Immune Dysfunction and Exclusion (TIDE) analysis, while sensitivity for chemotherapeutic agents was analyzed using oncoPredict. Finally, the expression patterns of hub genes were investigated by single-cell RNA sequencing (scRNA-seq) data analysis. Results: A total of 53 EMT-RDGs related to prognosis were identified, separating OS samples into two separate subgroups. The EMT-high subgroup showed favourable overall survival and more active immune response. Significant correlations were found between EMT-Related DEGs and functions as well as pathways linked to the development of OS. Additionally, a risk signature was established and OS patients were divided into two categories based on the risk scores. The signature presented a good predictive performance and could be recognized as an independent predictive factor for OS. Furthermore, patients with higher risk scores exhibited better sensitivity for five drugs, while no significant difference existed in immunotherapy response between the two risk subgroups. scRNA-seq data analysis displayed different expression patterns of the hub genes. Conclusion: We developed a novel EMT-Related risk signature that can be considered as an independent predictor for OS, which may help improve clinical outcome prediction and guide personalized treatments for patients with OS.

Comprehensive analysis of single-cell RNA and bulk RNA sequencing based on M2 tumor-associated macrophage and angiogenesis-related genes to assess prognosis and therapeutic response in lung adenocarcinoma.

M2 tumor-associated macrophage (M2 TAM), a crucial component of the tumor microenvironment, has a significant impact on tumor invasion and metastasis in the form of angiogenesis for lung adenocarcinoma (LUAD). In this study, both single-cell RNA and bulk RNA sequencing data were analyzed to identify 12 M2 TAM and angiogenesis-related genes (OLR1, CTSL, HLA-DPB1, NUPR1, ALOX5, DOCK4, CSF2RB, PTPN6, TNFSF12, HNRNPA2B1, NCL, and BIRC2). These genes were used to construct a prognostic signature, which was subsequently validated using an external cohort. Moreover, the immune profile analysis indicated that the low-risk group exhibited a distinct immune cell infiltration and relatively active status. Importantly, the prognostic signature was closely associated with PD-1, CTLA4, tumor mutation burden, and anti-cancer drug sensitivity. In summary, this study proposes a new prognostic signature for patients with LUAD based on M2 TAM and angiogenesis-related genes. The signature forecasts the prognosis of LUAD by an independent manner, reveals the potential molecular mechanisms involved in tumor immune-related functions, and offers appropriate clinical strategies for the treatment of patients with LUAD.

Changes in mucosa­associated lymphoid tissue 1 predicts therapeutic response and survival in patients with advanced melanoma receiving programmed cell death­1 inhibitor monotherapy.

Advanced melanoma is an aggressive and dangerous form of skin cancer, and programmed cell death-1 (PD-1) inhibitors are recommended treatment options for patients with advanced melanoma. Mucosa-associated lymphoid tissue 1 (MALT1) impairs CD8+ T-cell activation to induce immune escape, leading to a reduction in the antitumor effect of PD-1 inhibitors. The present study aimed to assess the prognostic implication of MALT1 in patients with advanced melanoma receiving PD-1 inhibitor monotherapy. Blood MALT1 levels were assessed using reverse transcription-quantitative PCR in 20 healthy controls (HCs) after enrollment and in 49 patients with advanced melanoma before (T0), as well as 2 months (T1) and 4 months after (T2) PD-1 inhibitor monotherapy. The maximum level of MALT1 in HCs (3.100) was used as the cut-off in patients with advanced melanoma. MALT1 levels at T0 were significantly increased in patients with advanced melanoma compared with in HCs (P<0.001). In patients with advanced melanoma, MALT1 was significantly decreased from T0 to T2 (P<0.001). Objective response rate (ORR) and disease control rate (DCR) were 28.6 and 59.2%, respectively. MALT1 levels at T1 were significantly negatively associated with overall therapeutic response (P=0.001), ORR (P=0.009) and DCR (P=0.004). MALT1 levels at T2 were significantly inversely associated with overall therapeutic response (P=0.021) and ORR (P=0.036). Moreover, MALT1 levels >3.100 at T0 (P=0.027) and T1 (P=0.045) were significantly associated with shorter progression-free survival (PFS), and MALT1 levels >3.100 at T1 were significantly associated with a poor overall survival (OS; P=0.022). Multivariate Cox regression analysis demonstrated that MALT1 levels at T0 (>3.100 vs. ≤3.100) were significantly associated with a poor PFS [hazard ratio (HR)=2.248; P=0.037], and MALT1 levels at T1 (>3.100 vs. ≤3.100) were significantly associated with a poor OS (HR=4.332; P=0.007). In conclusion, MALT1 levels are reduced following PD-1 treatment, and a high MALT1 level is associated with a poor therapeutic response and shorter survival in patients with advanced melanoma receiving PD-1 inhibitor monotherapy.

Personalized medicine in acromegaly: The ACROFAST study.

Medical treatment of acromegaly is currently performed through a trial-error approach using first generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response. Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated. METHODS AND SUBJECTS: prospective trial (21 university hospitals) comparing the effectiveness and time-to control of two treatment protocols during 12 months: A) A personalized protocol in which first option were fgSRLs as monotherapy or in combination with pegvisomant or, pegvisomant as monotherapy depending on the short Acute Octreotide Test (sAOT) results, tumor T2 Magnetic Resonance (MRI) signal or immunostaining for E-cadherin and, B) A control group with treatment always started by fgSRLs and the other drugs included after demonstrating inadequate control. RESULTS: Eighty-five patients participated; 45 in the personalized and 40 in the control group. More patients in the personalized protocol achieved hormonal control compared to those in the control group (78% vs 53%, p < 0.05). Survival analysis revealed a hazard ratio for achieving hormonal control adjusted by age and sex of 2.53 (CI 1.30-4.80). Patients from personalized arm were controlled in a shorter period of time (p = 0.01). CONCLUSION: Personalized medicine is feasible using a relatively simple protocol and allows a higher number of patients achieving control in a shorter period of time.

iGenSig-Rx: an integral genomic signature based white-box tool for modeling cancer therapeutic responses using multi-omics data.

Multi-omics sequencing is poised to revolutionize clinical care in the coming decade. However, there is a lack of effective and interpretable genome-wide modeling methods for the rational selection of patients for personalized interventions. To address this, we present iGenSig-Rx, an integral genomic signature-based approach, as a transparent tool for modeling therapeutic response using clinical trial datasets. This method adeptly addresses challenges related to cross-dataset modeling by capitalizing on high-dimensional redundant genomic features, analogous to reinforcing building pillars with redundant steel rods. Moreover, it integrates adaptive penalization of feature redundancy on a per-sample basis to prevent score flattening and mitigate overfitting. We then developed a purpose-built R package to implement this method for modeling clinical trial datasets. When applied to genomic datasets for HER2 targeted therapies, iGenSig-Rx model demonstrates consistent and reliable predictive power across four independent clinical trials. More importantly, the iGenSig-Rx model offers the level of transparency much needed for clinical application, allowing for clear explanations as to how the predictions are produced, how the features contribute to the prediction, and what are the key underlying pathways. We anticipate that iGenSig-Rx, as an interpretable class of multi-omics modeling methods, will find broad applications in big-data based precision oncology. The R package is available: https://github.com/wangxlab/iGenSig-Rx .

MRI monitoring of combined therapy with transcatheter arterial delivery of NK cells and systemic administration of sorafenib for the treatment of HCC.

This preclinical study explored the synergistic potential of sorafenib and NK cell chemoimmunotherapy to combat hepatocellular carcinoma (HCC) in a rat model. We aimed to enhance NK cell cytotoxicity through IL-12/18 cytokines supplementation and elucidate the underlying molecular mechanisms driving this collaborative antitumor action. Twenty-four Sprague-Dawley rats were divided into distinct treatment groups, receiving sorafenib via gavage and NK cells via catheterization of the proper hepatic artery. Tumor growth and treatment response were monitored through weekly MRI scans, including T1w, T2w, DCE, and DWI sequences. Histological examinations assessed tumor cell viability, apoptosis fraction, and microvessel density. The combined therapy demonstrated significant inhibition of tumor growth, angiogenesis, and induction of durable antitumor immunity compared to either modality alone. DCE-MRI and DWI revealed distinct alterations in tumor microvasculature, highlighting the effectiveness of the combination. Our findings highlight the promise of sorafenib-augmented NK cell chemoimmunotherapy as a potential therapeutic strategy for HCC management. The targeted delivery of IL-12/18 cytokines supplemented NK cells effectively enhanced cytotoxicity within the tumor microenvironment, leading to improved antitumor responses. Further investigation in clinical trials is warranted to validate these findings in human patients and explore the translational potential of this approach.

Prognostic and therapeutic roles of SETD2 in cutaneous melanoma.

BACKGROUND: Cutaneous melanoma (CM) is an aggressive form of skin cancer with limited treatment options for advanced stages. Prognostic markers that accurately predict patients' outcomes and guide therapeutic strategies are crucial for improving melanoma management. SETD2 (SET Domain-Containing Protein 2), a histone methyltransferase involved in chromatin remodeling and gene regulation, has recently emerged as a tumor suppressor. Its dysfunction is involved in oncogenesis in some cancers, but little is known about its functions in progression and therapeutic response of melanoma. METHODS: RNA-seq and clinical data from public database were used to evaluate the survival analysis, gene set enrichment, IC50 of therapeutics and immunotherapy response. SETD2 knock-out A375 cell line (A375SETD2ko) was developed by Crispr/cas9 and CCK-8 analysis and nude mice used to evaluate the proliferation and invasion of melanoma cells in vitro and in vivo, while Western blotting tested the MMR-related protein. RESULTS: SETD2 was commonly down-regulated in melanoma samples which demonstrated an unfavorable survival. Cells without SETD2 expression tend to have a more progressive and invasive behavior, with resistance to chemotherapy. However, they are more sensitive to tyrosine kinase inhibitors (TKIs). They also exhibit inflamed features with lower TIDE (Tumor Immune Dysfunction and Exclusion) score and higher tumor mutation burden (TMB), showing that these patients may benefit from immunotherapy. CONCLUSIONS: This study revealed that SETD2 dysfunction in melanoma implied a poor prognosis and chemotherapy resistance, but highly sensitive to TKIs and immunotherapy, highlighting the prognostic and therapeutic value of SETD2 in cutaneous melanoma.

Wnt/ß-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer.

Wnt/ß-catenin signaling is a critical pathway that influences development and therapeutic response of non-small cell lung cancer (NSCLC). In recent years, many Wnt regulators, including proteins, miRNAs, lncRNAs, and circRNAs, have been found to promote or inhibit signaling by acting on Wnt proteins, receptors, signal transducers and transcriptional effectors. The identification of these regulators and their underlying molecular mechanisms provides important implications for how to target this pathway therapeutically. In this review, we summarize recent studies of Wnt regulators in the development and therapeutic response of NSCLC.

Significance of High-Frequency Sonography for the Subclinical Progression of Rheumatoid Arthritis.

OBJECTIVES: This study aims to investigate the use of high-frequency sonography as a tool for detecting inflammatory and destructive changes in the hand and foot joints of patients with early and long-term RA. METHODS: This study employs a prospective cohort design involving 162 patients diagnosed with Rheumatoid arthritis (RA) who meet the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Patients were divided into two groups based on disease duration: Group 1 (n = 74) included patients with a disease duration of up to 2 years, or early РА (ERA;), Group 2 (n = 88) consisted of patients with a disease duration exceeding 2 years, or long-term persistent РА (LtRA). All patients underwent a clinical assessment of their joints, as well as radiography and arthrosonography, at the beginning of the study and again at 6 and 12 months later. RESULTS: In the general group of patients, ultrasound examination revealed signs of synovitis in the joints of the hands more frequently (66%) compared with clinical examination (56% by a number of swollen joints [NSJ] and 55% by a number of painful joints [NPJ], P < .01). After 6 months of treatment, 12% of the patients achieved full US remission and 24% achieved partial US remission. CONCLUSIONS: Within the scope of comprehensive RA diagnostics, arthrosonography of the joints of the hands and feet, utilizing a combination of greyscale and power Doppler, may surpass radiography in detecting early RA. This method allows for a more accurate assessment of disease activity and progression rates.

Prediction of response to promising first-line chemotherapy in ovarian cancer patients with residual peritoneal tumors: practical biomarkers and robust multiplex models.

BACKGROUND: Platinum/taxane (TC) chemotherapy with debulking surgery stays the mainstay of the treatment in ovarian cancer patients with peritoneal metastasis, and recently its novel modality, intraperitoneal carboplatin with dose-dense paclitaxel (ddTCip), was shown to have greater therapeutic impact. Nevertheless, the response varies among patients and consequent recurrence, or relapse often occurs. Discovery of therapeutic response predictor to ddTCip and/or TC therapy is eagerly awaited to improve the treatment outcome. METHODS: Using datasets in 76 participants in our ddTCip study and published databases on patients received TC therapy, we first validated a total of 75 previously suggested markers, sought out more active biomarkers through the association analyses of genome-wide transcriptome and genotyping data with progression-free survival (PFS) and adverse events, and then developed multiplex statistical prediction models for PFS and toxicity by mainly using multiple regression analysis and the classification and regression tree (CART) algorithm. RESULTS: The association analyses revealed that SPINK1 could be a possible biomarker of ddTCip efficacy, while ABCB1 rs1045642 and ERCC1 rs11615 would be a predictor of hematologic toxicity and peripheral neuropathy, respectively. Multiple regression analyses and CART algorithm finally provided a potent efficacy prediction model using 5 gene expression data and robust multiplex toxicity prediction models-CART models using a total of 4 genotype combinations and multiple regression models using 15 polymorphisms on 12 genes. CONCLUSION: Biomarkers and multiplex models composed here could work well in the response prediction of ddTCip and/or TC therapy, which might contribute to realize optimal selection of the key therapy.

Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies.

BACKGROUND: PCD-related long non-coding RNAs (PRLs) are rarely investigated in relation to clear cell renal carcinoma (ccRCC). As part of this study, we evaluated the immunological potential of PRL signatures as a biomarker for ccRCC prognosis and immunological function. MATERIALS AND METHODS: Data were downloaded from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases. A Pearson correlation analysis was conducted on the 27 PCD-associated genes to determine whether lncRNAs were significantly associated with PCD. Kaplan-Meier analysis, biological function identification, immune infiltration analysis, estimation of efficacy of immunotherapy and targeted drug screening, and exploration of the landscape of mutation status were conducted by analyzing the risk scores. RESULTS: Seven PRLs, LINC02747, AP001636.3, AC022126.1, LINC02657, LINC02609, LINC02154, and ZNNT1, were used to divide patients with ccRCC into groups with high and low risk. High-risk patients had a worse prognosis than low-risk patients, according to the results, and the PRL signature showed promising predictive ability. More immune cells were clustered in the high-risk group, whereas the immune cell function of the low-risk group was significantly suppressed. The high-risk group was less sensitive to immunotherapy, whereas the low-risk group had positive responses to most drugs. CONCLUSIONS: Collectively, we established and verified a PRL signature that could competently guide the prognostic survival and immunotherapy of ccRCC. In addition, molecular subtypes were determined for ccRCC based on PRL expression, which may help elucidate the underlying molecular mechanism of ccRCC and develop targeted treatments.

Sex differences in osteoarthritis prevalence, pain perception, physical function and therapeutics.

OBJECTIVE: Women have a higher prevalence of osteoarthritis (OA) and worse clinical courses than men. However, the underlying factors and therapeutic outcomes of these sex-specific differences are incompletely researched. This review examines the current state of knowledge regarding sex differences in OA prevalence, risk factors, pain severity, functional outcomes, and use and response to therapeutics. METHODS: PubMed database was used with the title keyword combinations "{gender OR sex} AND osteoarthritis" plus additional manual search of the included papers for pertinent references, yielding 212 references. Additional references were added and 343 were reviewed for appropriateness. RESULTS: Globally, women account for 60% of people with osteoarthritis, with a greater difference after age 40. The higher risk for women may be due to differences in joint anatomy, alignment, muscle strength, hormonal influences, obesity, and/or genetics. At the same radiographic severity, women have greater pain severity than men, which may be explained by biologically distinct pain pathways, differential activation of central pain pathways, differences in pain sensitivity, perception, reporting, and coping strategies. Women have greater limitations of physical function and performance than men independent of BMI, OA severity, injury history, and amount of weekly exercise. Women also have greater use of analgesic medications than men but less use of arthroplasty and poorer prognosis after surgical interventions. CONCLUSIONS: The recognition of sex differences in OA manifestations and management could guide tailoring of sex-specific treatment protocols, and analysis of sex as a biological variable in future research would enhance development of precision medicine.