Predictive Value For Response Research Articles

Predictive Value of Magnetic Resonance Complete Response After Neoadjuvant Therapy for Rectal Cancer.

Previous research has demonstrated that after neoadjuvant therapy for rectal cancer, the sensitivity of magnetic resonance complete response (mrCR) for detecting pathologic complete response (pCR) in the surgical specimen ranges from 74 to 94%. Patient and provider interest in nonoperative management of rectal cancer that responds favorably to neoadjuvant therapy has grown, necessitating stronger evidence for how well radiographic complete response truly predicts pCR. We sought to determine the current association between mrCR and pCR in locally advanced rectal cancer. We conducted a retrospective cohort study of patients with rectal adenocarcinoma who underwent neoadjuvant chemoradiation followed by index proctectomy at a single academic referral center from January 2012 to December 2021. Our primary outcomes were mrCR, defined as the absence of residual disease on restaging MRI, and pCR, defined as the absence of residual adenocarcinoma in surgical pathology specimens. Among 523 eligible patients, 157 met the inclusion criteria (38.9% females; 51.0% nonwhite; mean [SD] age, 58.6 [13.2] years). Overall, 8.9% of patients had mrCR and 7.0% had pCR. The sensitivity and positive predictive value of mrCR were 36.4% (95% CI: 10.9 to 69.2) and 28.6% (95% CI: 8.4 to 58.1). Our findings were qualitatively unchanged when only patients in the last 5 years of the study period were included. Study limitations include that neoadjuvant therapy regimens were not standardized and patients who were offered and elected to undergo nonoperative management were not included. The value of mrCR in predicting pathologic response following neoadjuvant therapy in locally advanced rectal cancer is low, and mrCR should be interpreted with caution when counseling patients about nonoperative management. Early, frequent surveillance is critical in patients who elect nonoperative management after mrCR.

Advanced Hemodynamic Monitoring in Polytraumatized Patients: A Comprehensive Review

INTRODUCTION Advanced hemodynamic monitoring plays a crucial role in optimizing the perioperative management of polytraumatized patients, allowing for real-time assessment of cardiovascular status and guiding goal-directed therapy. Traditional monitoring methods, while widely used, have significant limitations that may hinder their effectiveness in dynamic trauma scenarios. The introduction of non-invasive technologies such as continuous non-invasive arterial pressure monitoring and impedance cardiography has improved hemodynamic assessment, providing valuable insights with reduced procedural risks. Despite these advancements, challenges remain in terms of accuracy, clinical integration, and training requirements. OBJETIVE To evaluate the efficacy and applicability of advanced hemodynamic monitoring techniques during anesthesia in polytraumatized patients, highlighting their impact on perioperative outcomes. METHODS This is a narrative review which included studies in the MEDLINE – PubMed (National Library of Medicine, National Institutes of Health), COCHRANE, EMBASE and Google Scholar databases, using as descriptors: “Polytrauma anesthesia” AND “Advanced hemodynamic monitoring” OR “Goal-directed therapy” OR “Non-invasive cardiac output monitoring” OR “Trauma resuscitation strategies” in the last years. RESULTS AND DISCUSSION Results demonstrate that the application of advanced hemodynamic monitoring techniques enhances intraoperative hemodynamic stability and reduces perioperative complications by enabling individualized fluid management and early detection of deterioration. Studies indicate that dynamic indices such as stroke volume variation and pulse pressure variation offer superior predictive value for fluid responsiveness compared to static parameters. However, the widespread implementation of these technologies is influenced by economic constraints, technological limitations, and the need for specialized expertise. CONCLUSION In conclusion, advanced hemodynamic monitoring significantly contributes to improving outcomes in polytraumatized patients under anesthesia by providing continuous and accurate cardiovascular data. Addressing the challenges of implementation through structured training programs and cost-benefit analyses is essential for broader clinical adoption. Future research should focus on refining these technologies to enhance their reliability and applicability across diverse trauma care settings.

Comprehensive pan-cancer analysis reveals NTN1 as an immune infiltrate risk factor and its potential prognostic value in SKCM

Netrin-1 (NTN1) is a laminin-related secreted protein involved in axon guidance and cell migration. Previous research has established a significant connection between NTN1 and nervous system development. In recent years, mounting evidence indicates that NTN1 also plays a crucial role in tumorigenesis and tumor progression. For instance, inhibiting Netrin-1 has been shown to suppress tumor growth and epithelial-mesenchymal transition (EMT) characteristics in endometrial cancer. To further elucidate the influence of genes on tumors, we utilized a variety of machine learning techniques and found that NTN1 is strongly linked to multiple cancer types, suggesting it as a potential therapeutic target. This study aimed to elucidate the role of NTN1 in pan-cancer using multi-omics data and explore its potential as a prognostic biomarker in SKCM. Analysis of the TCGA, GTEx, and UALCAN databases revealed significant differences in NTN1 expression at both the mRNA and protein levels. Prognostic value was evaluated through univariate Cox regression and Kaplan–Meier methods. Mutation and methylation analyses were conducted using the cBioPortal and SMART databases. We identified genes interacting with and correlated to NTN1 through STRING and GEPIA2, respectively. Subsequently, we performed GO and KEGG enrichment analyses. The results suggested that NTN1 might be involved in crucial biological processes and pathways related to cancer development and progression, including cell adhesion, axon guidance, immune response, and various signaling pathways. We then explored the correlation between NTN1 and immune infiltration as well as immunotherapy using the ESTIMATE package, TIMER2.0, TISIDB, TIDE, TIMSO, and TCIA. The relationship between NTN1 and tumor heterogeneity, stemness, DNA methyltransferases, and MMR genes was also examined. Lastly, we constructed a nomogram based on NTN1 in SKCM and investigated its association with drug sensitivity. NTN1 expression was significantly associated with tumor immune infiltration, molecular subtypes, and clinicopathological features in various cancers. Genetic analysis revealed that Deep deletions were the most common type of NTN1 alteration. Additionally, a positive correlation was observed between NTN1 CNAs and its expression levels. In most cancers, NTN1 showed positive correlations with immune and stromal scores, as well as with specific immune cell populations. Its predictive value for immunotherapy response was comparable to that of tumor mutational burden. Furthermore, NTN1 exhibited positive correlations with tumor heterogeneity, stemness, DNA methyltransferase genes, and MMR genes. In SKCM, NTN1 was identified as an independent risk factor and demonstrated potential associations with multiple drugs. NTN1 exhibits substantial clinical utility as a prognostic marker and indicator of immune response across various tumor types. This comprehensive analysis provides insights into its potential implications in pan-cancer research.

P0596 Fecal bile acids predict the therapeutic effect of biological agents in patients with ulcerative colitis

Abstract Background Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the colon. Infliximab or vedolizumab is recommended for treatment of moderate to severe UC, but has a primary or secondary non-response rate. Receiving early predictions on treatment efficacy can offer substantial support for patients’ therapeutic interventions. We aim to use fecal bile acids to identify predictive biomarkers. Methods Fecal samples were collected from 55 UC patients hospitalized in the Second Hospital of Hebei Medical University and 10 healthy volunteers. UC patients were divided into clinical response group and clinical non-response group according to the therapeutic effect of biologics. Quantitative detection of target bile acids was performed on fecal samples. The bile acid levels of the two groups were compared, and the bile acids that predicted the therapeutic effect were screened by orthogonal partial least squares discriminant analysis (OPLS-DA) and the analysis of receiver working characteristic curve. Results Compared with healthy adults, patients with UC showed decreased total fecal bile acids, increased primary bile acids, and decreased secondary bile acids. After treatment with biologics, there was a decrease in primary bile acids and an increase in secondary bile acids. In comparison between clinical responders and non-responders, fecal lithocholic acid and deoxycholic acid were significantly increased, and the ratio of primary bile acids to secondary bile acids was significantly decreased. When deoxycholic acid was higher than 29.55 ug/g or lithocholic acid was higher than 0.195 ug/g, it had predictive value for clinical response. Conclusion Fecal bile acids, especially deoxycholic acid and lithocholic acid, may serve as novel biomarkers for predicting the therapeutic effect of biological agents in UC patients.

Improvement in serum eosinophilia is observed in clinical responders to ustekinumab but not adalimumab in inflammatory bowel disease.

In inflammatory bowel disease (IBD), the number of eosinophils increases in the lamina propria of the intestinal tract, but their specific patho-mechanistic role remains unclear. Elevated blood eosinophil counts in active IBD suggest their potential as biomarkers for predicting response to biological therapies. This study evaluates blood eosinophil count trends and their predictive value for clinical response and endoscopic improvement in patients with IBD receiving ustekinumab or adalimumab induction therapy. Participant-level data from phase 3 and 4 clinical trials (UNIFI, SEAVUE, VARSITY) evaluating ustekinumab and adalimumab for moderate-severe Crohn's disease (CD) and ulcerative colitis (UC) were used. The primary outcome was clinical response, defined by reductions in disease activity scores. Eosinophil counts were compared between responders and non-responders at multiple time points using t-tests. Logistic regression assessed the odds of achieving a clinical response based on baseline eosinophil counts. Among patients treated with ustekinumab for UC, responders had significantly higher baseline eosinophil counts compared to non-responders (0.21 × 109/L vs 0.18 × 109/L, P = .042). By week 8, responders showed a greater absolute (-0.07 × 109/L vs -0.01 × 109/L, P < .001) and percent decline (-33.33% vs -5.55%, P = .027) in eosinophil counts. In CD, ustekinumab responders also had higher baseline eosinophil counts and showed significant reductions by week 8. However, no significant differences in eosinophil counts were observed among CD patients treated with adalimumab or UC patients treated with vedolizumab. Eosinophil reduction was identified as a marker for early response to ustekinumab in both UC and CD, but not adalimumab. No difference was observed among UC patients treated with vedolizumab either. Targeting the IL-12/IL-23 pathway may be more effective in managing eosinophil-associated inflammation in IBD.

Apparent diffusion coefficient and magnetic resonance imaging characteristics in predicting response to radiosurgery in patients with vestibular schwannomas.

Predicting treatment response in patients with vestibular schwannomas (VSs) remains challenging. This study aimed to evaluate the use of pre-treatment normalized apparent diffusion coefficient (nADC) values and magnetic resonance (MR) imaging characteristics in predicting treatment outcomes in patients with VSs undergoing radiosurgery. The MR images of 44 patients with VSs who underwent radiosurgery at our institution were retrospectively reviewed, and the patients were categorized into tumor control (n = 28) and progression (n = 16) groups based on treatment response after treatment initiation, with a median follow-up duration of 29.5 (13-115)months. Pre-treatment nADC values for the whole tumor and solid portion of the tumor were assessed for predictive significance. MRI characteristics were analyzed, including hemorrhage status, tumor morphology, and post-treatment loss of central enhancement. Interobserver reliability was also evaluated. Early post-treatment enlargement was associated with tumor progression (p = .024). The mean pre-treatment nADC values for the solid part of the tumor were significantly higher in the tumor control group than in tumor progression group (1.32 vs 1.05, p = .005). The receiver operating characteristic curve analysis revealed a mean nADC of 1.18 as an optimal cutoff, with sensitivity and specificity of 76.2% and 86.7%, respectively, in predicting treatment response. The mean nADC values for the solid part of the tumor demonstrated predictive value for treatment response, with implications for treatment planning. Notably, early post-treatment enlargement was correlated with tumor progression. Incorporating these findings into clinical practice may refine treatment strategies for patients with VSs undergoing radiosurgery.

Lubricity potentials of Azadirachta indica (neem) oil and Cyperus esculentus (tiger nut) oil extracts and their blends in machining of mild steel material.

Friction amongst the cutting tool and workpiece in metal machining produces heat that reduces tool life and workpiece integrity. Consequently, non-biodegradable soluble mineral oil is predominantly used as a lubricant to enhance machining operations. Nevertheless, recent investigations focus on environmentally friendly biodegradable oils for lubrication. Therefore, this study examines the lubricity potential of neem oil, tiger nut oil, and their blends in machining mild steel. It also evaluates the performance characteristics of individual bio-oils and their blends against conventional soluble mineral oil and dry-drilling methods. Neem and tiger nut oils were extracted using pressing and solvent methods, followed by an analysis of their physiochemical properties. The experimental design utilized the I-Optimal custom design and simplex lattice design (SLD) for the individual and blended oils respectively. Response Surface Methodology (RSM) was applied for optimization, with feed rate, oil type, and spindle speed as independent variables, and cutting temperature, surface finish, depth of cut, chip thickness, chip thickness ratio, cutting speed, and material removal rate as response variables. The optimal cutting conditions were predicted at a spindle speed of 695rpm, feed rate of approximately 0.4735, and neem oil being the cutting fluid. The predicted response values were cutting temperature - 33.5°C, surface roughness - 2.65μm, depth of cut - 41.4825mm, chip thickness - 0.18951mm, chip thickness ratio - 269.586, cutting speed - 17.4695m/min, and material removal rate - 2.38025E-05. Results indicated neem oil surpassed tiger nut oil and conventional oils in minimizing cutting temperatures and enhancing surface quality, achieving a desirability value of 0.85428 under optimal conditions. Moreover, an 80/20 blend of neem and tiger nut oils exhibited improved performance, attaining a desirability value of 0.992, underscoring its potential as an effective cutting fluid. The findings advocate for the use of bio-based cutting fluids in machining operations, indicating environmental and economic advantages while promoting future research into alternative agro-based solutions. However, limitations regarding material applicability and the necessity for further investigation into the micro-structural effects of cutting fluids on diverse engineering materials are acknowledged.

Multifidelity co-kriging metamodeling based on multivariate data fusion for dynamic fit improvement of injection mechanism in squeeze casting

To improve the dynamic fit the injection mechanism in a squeeze casting machine, this paper proposes a novel multifidelity co-kriging (MFCK) metamodeling method, which fuses high-fidelity measured data with low-fidelity simulated data and considers data uncertainty and multivariate correlation influence to accurately predict response values when experimental sample data are insufficient. An MFCK model was established to predict the deformation and dynamic fit clearance, by selecting experimental and simulated values of deformation and temperature as the principal and covariates for correlation testing. The results indicate that the proposed MFCK model significantly improved the prediction accuracy by 34.18 %, 73.53 %, 41.57 % and 37.93 %, respectively, compared with the ordinary kriging model and finite element method. This method was applied to the multicycle injection process of a 2,500-kN squeeze casting machine, revealing the variation law of the fit clearance. The MFCK model improved the prediction accuracy of the fit clearance by 72.7 %, which is beneficial for process control. The accuracy and industrial applicability of the proposed MFCK method was thus verified.

Does FDG PETCT have a predictive value for neoadjuvant chemotherapy response in nonmetastatic breast cancer?

A pathological complete response (pCR) rate after neoadjuvant chemotherapy (NAC) is important for the prognosis of early-stage breast cancer. The prediction of an NAC response plays a key role in managing neoadjuvant treatment. The aim of this study is to investigate the predictive value of the baseline PETCT FDG (F-18 fluoro-deoxy-glucose (FDG) positron emission tomography/computed tomography) SUVmax (the maximum standardized uptake value) for pCR after NAC in early-stage breast cancer. The patients who performed PETCT before NAC were included in this retrospective study. The basal PETCT SUVmax values were divided into two categories based on the cutoff points of ≥ 8.77 or < 8.77, namely the low SUV max group and the high SUV max group. These two groups were compared according to the general characteristics. The impact of the PETCT SUVmax values on pCR was determined with logistic regression analyses. One hundred forty-eight patients who performed PETCT before NAC were included in this retrospective study. Eighty-one patients were in the low SUV max group and 67 patients were in the high SUVmax group. The pCR trended toward a higher rate in the high SUVmax group than in low SUVmax group but it was not statistically significant (p = 0.052). The baseline PETCT SUVmax value was an independent predictive factor for pCR. (p = 0.025). PETCT SUVmax may be a factor for the predicting complete response to neoadjuvant treatment in early-stage breast cancer.

Predictive value of longitudinal systemic inflammatory markers for pathologic response to neoadjuvant PD-1 blockade in resectable non-small cell lung cancer.

Identifying biomarkers to predict responses for neoadjuvant immunotherapy in resectable non-small cell lung cancer (NSCLC) is under intensive study. Considering the interplay between cancer, inflammation, and immunosuppression, we hypothesized that circulating and imaging inflammatory markers could serve as indicators of anti-tumor immune responses, and thus conducting an exploratory study to reveal the predictive value of combining longitudinal systemic inflammatory markers in stratifying pathologic response to neoadjuvant sintilimab. We retrospectively reviewed 36 patients (29 male and seven female) with NSCLC (stage IA-IIIB) who underwent pre- and post-treatment peripheral blood tests and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans before and after two cycles of neoadjuvant sintilimab (registration number: ChiCTR-OIC-17013726). The neutrophil-to-lymphocyte ratio (NLR), immune-related adverse events (irAEs) on imaging, and lymphoid organ metabolism [spleen-to-liver ratio (SLR) and bone marrow-to-liver ratio (BLR)] were evaluated to examine their predictive value for the major pathologic response (MPR). Significant variables were used to classify patients into low, intermediate, and high inflammatory burden groups for stratifying pathologic regression and tumor-infiltrating immune cells abundance in the tumor microenvironment. Spearman's correlation analysis was performed to explore the correlation between systemic inflammatory markers, primary tumor metabolism, and tumor-infiltrating immune cells abundance at various time points. Of the 36 enrolled patients, 13 (36.1%) exhibited MPR. ΔNLR% was a significant negative predictor of MPR (P=0.047) and negatively correlated with pathologic regression (r=-0.34, P=0.045). Pre- and post-treatment SLRs were potential negative predictors of MPR (P=0.06; P=0.055) and negatively correlated with pathologic regression (r=-0.30, P=0.07; r=-0.31, P=0.06). The high inflammatory burden group (pre-treatment SLR >0.83 and ΔNLR% >-17%) had the lowest pathologic regression (P=0.01) and the highest infiltration abundance of pre-treatment CD68+ macrophage (P=0.01-0.04). irAEs on imaging did not have significant effects on MPR and pathologic regression in overall and per-organ analyses. The combination of pre-treatment SLR and ΔNLR% demonstrates predictive value in stratifying pathologic response to neoadjuvant immunotherapy in resectable NSCLC. The high inflammatory burden group had the lowest pathologic regression and the pre-treatment immunosuppressive microenvironment with macrophage enrichment.

Comprehensive Analysis Reveals That ISCA1 Is Correlated with Ferroptosis-Related Genes Across Cancers and Is a Biomarker in Thyroid Carcinoma.

ISCA1 (Iron-Sulfur Cluster Assembly 1) is involved in the assembly of iron-sulfur (Fe-S) clusters, which are vital for electron transport and enzyme activity. Some studies suggest the potential involvement of ISCA1 in tumor progression through interactions with ferroptosis-related genes (FRGs) and the tumor immune microenvironment (TME). However, there has been no systematic analysis of its role in FRGs and the TME or its predictive value for prognosis and immunotherapy response across different cancer types. In this study, we analyzed the expression and prognosis of ISCA1 RNA, CNV, methylation, and protein in multiple tumor tissues via data from the TCGA and CPTAC databases and clinical information. We conducted a comprehensive analysis of the correlations between ISCA1 and FRGs, immune-related genes (including immune regulatory genes and immune checkpoint genes), immune cell infiltration, immune infiltration scores, tumor stemness, and genomic heterogeneity. We performed drug prediction and validation through molecular docking and molecular dynamics analysis to identify candidate drugs that could promote or inhibit ISCA1 RNA expression. Our findings revealed that ISCA1 could serve as a biomarker in thyroid carcinoma, play a role with different FRGs in various cell types, and mediate different ligand-receptor pathways for cell-cell communication. Overall, our study highlights the potential of ISCA1 as a novel biomarker for predicting prognosis and immunotherapeutic efficacy in thyroid carcinoma and suggests its potential for developing novel antitumor drugs or improving immunotherapy.

Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients

PurposeTo investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after treatment initiation in CheckMate 069, 066, and 067 studies. Patients and methodsTreatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed. Association between characteristics and response was evaluated by univariate and multivariate analyses. ResultsResponse rates at any time were 58 % (239/409) for nivolumab+ipilimumab and 44 % (230/526) for nivolumab monotherapy. In 12-month landmark analyses, 5-year OS rates for responders versus non-responders were 82 % versus 40 % with nivolumab+ipilimumab (HR=0.23 [95 % CI, 0.15–0.35]) and 76 % versus 32 % with nivolumab monotherapy (HR=0.22 [95 % CI, 0.16–0.31]). PFS rates were 83 % versus 32 % and 69 % versus 46 %, respectively. Similar strong associations between response at 3 and 6 months and 5-year OS and PFS were also observed with more than 70 % of the responses observed in the first 3 months. Response rates correlated with baseline LDH and PD-L1 status by multivariate analysis but the association between response and long-term survival was maintained in landmark analyses even among patients with high LDH and low PD-L1 expression. ConclusionClinical response evaluated in the first months of therapy is a strong predictor of long-term survival, even in patients with poor prognostic biomarkers.

Can Circulating Tumor DNA Improve the Predictive Value of Interim Response in Patients with Advanced Hodgkin Lymphoma and PET-2 DS3?

Background: Analysis of 441 patients with classical HL in advanced stages from the Czech Hodgkin Lymphoma Registry treated with 6 or 4 cycles of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) according to the interim PET-2 has shown that within patients that received 4 cycles of eBEACOPP, there is a trend for a higher 5-year progression-free survival (PFS) in patients with PET-2 Deauville score (DS) 1-2 in comparison to patients with PET-2 DS3 (91% [95% CI 84-99] vs. 78% [95% CI 64-95], p=0.061), accepted for ISHL13. To better stratify patients with PET-2 DS3 into 4 or 6 cycles of eBEACOPP, we analyzed circulating tumor DNA (ctDNA) within the ongoing trial NCT06263530 and correlated it with interim PET-2 results. Methods: To analyze ctDNA levels and its dynamics, we collected peripheral blood from 67 patients with classical HL in advanced stages III/IV, including clinical stages IIB with massive mediastinal tumor and/or extranodal involvement. 60 patients received eBEACOPP (30 patients 4 cycles and 30 patients 6 cycles), 4 patients received combination of eBEACOPP (4 cycles) and ABVD (2 cycles), and only 3 patients received 6 cycles of ABVD. Blood samples were collected at diagnosis, after two cycles of chemotherapy, and at the end of treatment (EoT). Following cell free DNA extraction, levels of ctDNA were determined using a custom panel of 538 genes frequently altered in lymphomas utilizing next generation sequencing-based CAPP-Seq (CAncer Personalized Profiling by deep Sequencing) approach. Plasma ctDNA levels were consequently correlated with PET results at the same timepoints. Results: Out of 67 patients (all white race, male gender 39 patients, median age at diagnosis 33 with range 19 - 70 years) 56 achieved PET-2 metabolic complete remission - CMR (30 patients DS1-2 and 26 patients DS3) and 11 patients achieved partial remission - PR (DS4-5). At the end of chemotherapy, the number of CMR increased to 61, 5 patients were in PR, and unknown response was achieved in 1 patient. Overall, 9 patients relapsed/progressed after the first-line treatment (with interim PET-2: DS2 in 3 patients, DS3 in 2 patients, and DS4-5 in 4 patients). Preliminary analysis suggests that ctDNA might improve PET-2 based disease status evaluation and patient stratification. Correlation of ctDNA with interim PET-2 and EoT PET will be presented. Conclusion: ctDNA is a promising sensitive tool to better stratify treatment of patients with Hodgkin lymphoma. This work was supported by grants AZV NU22-03-00182 from the Ministry of Health of the Czech Republic, MH CZ DRO (FNOl_00098892, VFN00064165), National Institute for Cancer Research (EXCELES - LX22NPO5102), Cooperatio Program (research areas Oncology and Haematology and Biology), and SVV 260637.

Dewatering and drying of Kombucha Bacterial Cellulose for preparation of biodegradable film for food packaging

Kombucha Bacterial Cellulose (KBC), obtained from waste products of kombucha fermentation, has potential applications in diverse fields. The present study used tea waste as a raw material for producing kombucha-like beverages and bacterial cellulose (BC). The in-situ dewatering and drying operations were performed to remove the high-water content from fermented KBC. Herein, the performance of BC in pressure-driven separation has been investigated as a function of dewatering pressure, drying temperature, and drying time in a multifunctional filtration cell. The Central Composite Design (CCD) was used to optimize the dewatering and drying parameters. The optimum conditions were found to be 4 bar pressure, 99 °C drying temperature, and 5 min drying time with a desirability value of 0.921. The predicted response values agreed with actual responses within 2.3–2.7 %. The dried films were prepared at optimized conditions and used to investigate thickness, density, mechanical properties, Fourier transform infrared, and scanning electron microscopy. The properties of KBC film varied as fermentation days increased. The KBC films' transparency decreased as thickness and density increased. The KBC film exhibits excellent mechanical properties such as tensile strength, maximum load, extension at the break, load at the break, and Young's modulus. The KBC films have been reported to be biodegradable and non-toxic and may be used for food packaging. Moreover, the present study successfully demonstrated that KBC packaging material could extend the shelf life of tomatoes by 13–15 days under accelerated conditions.

A flattening systolic blood pressure response at the end of ramp exercise testing is not associated with all-cause mortality

Abstract Purpose Systolic blood pressure (SBP) is expected to rise linearly during ramp exercise, but sometimes plateaus before the end of exercise. We aimed to examine the predictive value of a plateauing SBP response at the end of a cycle exercise test. Methods We analyzed 9,001 consecutive patients aged ≥18 years with maximal cycle ergometer ramp tests, after excluding subjects with valvulopathy, pacemaker, arrhythmia during the test, or body mass index (BMI) &amp;gt;40kg/m², as well as tests with resting SBP &amp;lt;80mmHg or &amp;gt;200mmHg, exercise SBP &amp;lt;100 mmHg, &amp;lt;2 SBP measurements during the second half of the test or a test duration &amp;lt;4 minutes. The data were cross-linked with nationwide registries for mortality and in- and outpatient hospital diagnoses. The difference in SBP between the two last SBP measurements was standardized to the difference in Watts between the same time points, categorized as i) an SBP decrease (drop), ii) an SBP increase of &amp;lt;2.5 mmHg per 10 Watts increase (flat), iii) an SBP increase of 2.5-15 mmHg/10 Watts (intermediate), and iv) an SBP increase &amp;gt;15 mmHg/10 Watts representing the 97.5th percentile (steep). Hazards ratios (HR, [95% confidence interval, CI]) for all-cause mortality were calculated, stratified for exercise capacity (peak Watt % of predicted) with the intermediate SBP response as reference. Adjustments were made for age, sex, BMI, resting SBP, baseline diagnosis of ischemic heart disease, heart failure, chronic obstructive pulmonary disease, and the use of beta-blockers or anti-hypertensive medication. Results Decreasing, flat, intermediate, and steep SBP responses at the end of exercise were present in 1.1%, 25.6%, 70.8% and 2.5% of patients respectively (Table 1). During median follow-up 8.6 years (interquartile range 5.9–11.6 years) there were 844 deaths. When compared to an intermediate SBP response, a flat SBP response was not associated with all-cause mortality in any of the exercise capacity strata: lowest tertile of Wmax%pred unadjusted HR 0.88 (95% CI 0.69–1.11), middle tertile HR 0.91 (95% CI 0.66–1.24), and highest tertile HR 0.95 (95% CI 0.64–1.41), with HRs remaining non-significant after adjustment for covariates (Table 2). Conclusion In patients referred for exercise testing, a flattening SBP response at the end of exercise was not associated with increased all-cause mortality risk compared to an intermediate SBP response, consistent across the different exercise capacity strata.

Halving Time of BCR-ABL Transcripts as a Precise Predictor for Deep Molecular Response in Patients with Chronic Myeloid Leukemia Treated with TKI

To investigate the early predictive value of halving time (HT) of BCR-ABLIS for deep molecular response (DMR) in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitor (TKI). The continuous data of newly diagnosed CML patients with complete case data and first-line imatinib treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2014 to June 2022 were retrospectively analyzed. Combined with the clinical characteristics of the patients and the efficacy analysis at each time point, a logistic regression model was used to explore the independent influencing factors of DMR, and combined HT of BCR-ABLIS with BCR-ABLIS level at 3 months to predict DMR of the patients. Univariate and multivariate analyses showed that HT and 3-month BCR-ABLIS levels were independent influencing factors for MR4, MR4.5, and stable MR4.5 ( P < 0.05). ROC curve analysis determined that the best cut-off value of HT was 28 days. Compared with patients with HT>28 d, patients with HT≤28 d were more likely to obtain DMR at 2, 3, and 5 years, respectively (74.2% vs 27.3%, 71.2% vs 22.7%, and 63.6% vs 25.0%, all P < 0.001). The patients were divided into 4 groups according to BCR-ABLIS levels at 3 months and HT. Kaplan-Meier analysis showed that the patients in the BCR-ABLIS≤10% and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABLIS≤10% and HT>28 d group (P < ＜0.05); Patients in the BCR-ABLIS>10% and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABLIS＞10% and HT>28 d group ( P < 0.05). In addition to BCR-ABLIS level, HT of BCR-ABLIS can be used as another important predictor of treatment efficacy in CML patients. The combination of BCR-ABLIS level and HT has a more accurate predictive value for long-term molecular response of CML patients after TKI treatment.

Evaluating the feasibility and predictive accuracy of biodynamic imaging to platinum-based chemotherapy response in esophageal adenocarcinoma.

Esophageal cancer management lacks reliable response predictors to chemotherapy. In this study we evaluated the feasibility and accuracy of Biodynamic Imaging (BDI), a technology that employs digital holography as a rapid predictor of chemotherapy sensitivity in locoregional esophageal adenocarcinoma. Pre-treatment endoscopic pinch biopsies were collected from patients with esophageal adenocarcinoma during standard staging procedures. BDI analyzed the tumor samples and assessed in vitro chemotherapy sensitivity. BDI sensitivity predictions were compared to patients' pathological responses, the gold standard for determining clinical response, in the surgically treated subset (n=18). BDI was feasible with timely tissue acquisition, collection, and processing in all 30 enrolled patients and successful BDI analysis in 28/29 (96%) eligible. BDI accurately predicted chemotherapy response in 13/18 (72.2%) patients using a classifier for complete, marked, and partial/no-response. BDI technology had 100% negative predictive value for complete pathological response hence identifying patients unlikely to respond to treatment. BDI technology can potentially predict patients' response to platinum chemotherapy. Additionally, this technology represents a promising step towards optimizing treatment strategies for esophageal adenocarcinoma patients by pre-emptively identifying non-responders to conventional platinum-based chemotherapy.

Evaluation of serum fibronectin levels and fibronectin gene polymorphism in patients receiving intravesical BCG therapy for non-muscle invasive bladder cancer and its prognostic value

BackgroundBladder cancer continues to be a significant health issue, leading to ongoing research into novel biomarkers and treatment strategies. This study aims to evaluate the potential of serum fibronectin levels and fibronectin gene polymorphisms as biomarkers for predicting the recurrence and treatment response in patients with NMIBC undergoing intravesical BCG therapy.MethodsBetween June 2022 and December 2022, data of 73 patients who applied to the Mersin University Urology Clinic due to NMIBC and were followed and treated in our clinic, receiving intravesical BCG treatment, when necessary, as well as 56 individuals without any malignancy, were prospectively examined. Serum fibronectin levels were measured using the enzyme-linked immunosorbent assay method. PCR testing was applied for the fibronectin gene RS10202709 and RS 35,343,655 gene polymorphisms by using Real-Time PCR.ResultsThe mean serum fibronectin level in the patient group was 76.794 ± 66.998ng/ml. Simultaneously, it was 50.486 ± 25.156ng/ml in the control group, and these differences in serum fibronectin levels were statistically significant(p = 0.003). Out of the 73 patients included in the study, recurrence of bladder cancer was observed in 53 of them. They were divided into two groups based on the recurrence times: early recurrence and late recurrence. The mean fibronectin level in the early recurrence group was 102 ± 86.1 ng/ml, while it was 44.7 ± 11.8 ng/ml in the late recurrence group. Emphasize the significance of the higher fibronectin levels in the early recurrence group by stating, patients with early recurrence exhibited significantly higher serum fibronectin levels compared to those with late recurrence (p < 0.001), suggesting a potential role for fibronectin as a prognostic biomarker.ConclusionsThe statistically higher concentrations of serum fibronectin levels in patients with bladder cancer observed in our study are a noteworthy finding. These findings suggest that serum fibronectin levels could serve as a valuable prognostic biomarker for early recurrence in NMIBC patients, although their predictive value for BCG treatment response remains limited.

Optimization of Motor Rotor Punch Wear Parameters Based on Response Surface Method

To reduce the wear of the motor rotor punching punch and ensure the efficiency is the highest in actual production, the finite element analysis software Deform-3Dv11 is used to simulate the punch wear based on the Archard model theory. With punch wear as the response target and punch speed, punch clearance, and punch edge fillet as the main factors, 17 groups of response surface Box–Behnken test designs are established, as well as a quadratic polynomial regression model between the main factors and the response. The results revealed that: the influence of various parameters on punch wear is in the order of punch edge fillet C &gt; punch clearance B &gt; punch speed A; the order of the interactive influence of various factors is as follows: punch speed and punch edge fillet AC &gt; punch speed and punch clearance AB &gt; punch clearance and punch edge fillet BC. The optimal blanking process combination obtained by using Design-Expert13 software is as follows: blanking speed 50 mm/s, blanking clearance 0.036 mm, and die cutting edge rounded corner 0.076 mm; the predicted response surface value is 6.95 × 10−12 mm. Through simulation verification, the actual optimized simulation value is 6.93 × 10−12 mm, with an absolute relative error of 2.5% for the predicted response value. Moreover, the optimized simulation value is reduced by 30.4% compared to the one before optimization, effectively reducing the punch wear of the motor rotor punching forming and providing a theoretical foundation for further wear optimization.

Candidate Biomarkers for Response to Treatment in Psoriatic Disease.

To determine whether biologic therapy alters serum C-X-C motif chemokine ligand 10 (CXCL10), matrix metalloproteinase 3 (MMP3), S100 calcium-binding protein A8 (S100A8), acid phosphatase 5 (ACP5), and C-C motif chemokine ligand 2 (CCL2) levels in patients with psoriatic arthritis (PsA) and cutaneous psoriasis without arthritis (PsC), and whether baseline levels of these proteins predict response to treatment for PsA. We included (1) patients with PsA taking tumor necrosis factor inhibitors (TNFi), interleukin 17 inhibitors (IL-17i), methotrexate (MTX), and those who were untreated with bDMARDs or csDMARDs; (2) patients with PsC taking bDMARDs; and (3) matched patients with PsC who were not treated with bDMARDs or csDMARDs. Serum samples at baseline and at the 3- to 6-month follow-up visit were retrieved from the biobank. Protein levels were quantified using a Luminex multiplex assay. We compared follow-up vs baseline protein levels within groups and change in levels between groups. For the predictive potential of the biomarkers, we developed logistic regression classification models. Response to treatment was defined as (1) achieving low disease activity or remission (according to the Disease Activity Index for Psoriatic Arthritis); (2) ≥ 75% reduction in Psoriasis Area and Severity Index; and (3) ≥ 50% reduction in actively inflamed joint count. In PsA, TNFi reduced serum levels of all 5 proteins, IL-17i increased ACP5 and CCL2, and MTX reduced MMP3. Changes in MMP3 and S100A8 levels were significantly different between untreated PsA and matched biologic-treated PsA (P < 0.05). There were no significant differences between treated or untreated patients with PsC. Baseline levels of CXCL10, MMP3, S100A8, and ACP5 had good predictive value (area under the curve > 0.80) for response to biologics in patients with PsA. Treatment with biologics and MTX affect serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in patients with PsA. MMP3, S100A8, ACP5, and CXCL10 have potential use as serum biomarkers to predict response to treatment for PsA.