Enhance Response Rates Research Articles

Enhancing Cancer Treatment Through Combined Approaches: Photodynamic Therapy in Concert with Other Modalities.

This review explores the role of photodynamic therapy (PDT) as an adjunctive treatment for cancers, with a focus on its potential to enhance the effects of established therapies like chemotherapy, surgery, and radiotherapy. Given the limitations of conventional cancer treatments, PDT's ability to improve therapeutic outcomes through combination strategies is examined. In cancers such as lung, breast, cholangiocarcinoma, and cervical, PDT shows promise in enhancing response rates, reducing recurrence, and minimizing adverse effects when used alongside standard modalities. This study highlights current findings on PDT's mechanisms in complementing chemotherapy, augmenting surgical precision, and enhancing radiotherapeutic effects, thus offering a multi-faceted approach to cancer treatment. Additionally, insights into the clinical application of PDT in these cancers emphasize its potential for reducing tumor resistance and supporting more effective, personalized care. By providing an overview of PDT's synergistic applications across diverse cancer types, this review underscores its emerging significance in oncology as a tool to address traditional treatment limitations. Ultimately, this review aims to inform and inspire researchers and clinicians seeking to refine and innovate cancer therapy strategies through PDT integration, contributing to the advancement of more effective, synergistic cancer treatments.

Effects of simulated microgravity on colorectal cancer organoids growth and drug response

Cellular and molecular dynamics of human cells are constantly affected by gravity. Alteration of the gravitational force disturbs the cellular equilibrium, which might modify physiological and molecular characteristics. Nevertheless, biological responses of cancer cells to reduced gravitational force remains obscure. Here, we aimed to comprehend not only transcriptomic patterns but drug responses of colorectal cancer (CRC) under simulated microgravity. We established four organoids directly from CRC patients, and organoids cultured in 3D clinostat were subjected to genome wide expression profiling and drug library screening. Our observations revealed changes in cell morphology and an increase in cell viability under simulated microgravity compared to their static controls. Transcriptomic analysis highlighted a significant dysregulation in the TBC1D3 family of genes. The upregulation of cell proliferation observed under simulated microgravity conditions was further supported by enriched cell cycle processes, as evidenced by the functional clustering of mRNA expressions using cancer hallmark and gene ontology terms. Our drug screening results indicated an enhanced response rate to 5-FU under conditions of simulated microgravity, suggesting potential implications for cancer treatment strategies in simulated microgravity.

Investigating In Vivo Tumor Biomolecular Changes Following Radiation Therapy Using Raman Spectroscopy.

Treatment resistance is a major bottleneck in the success of cancer therapy. Early identification of the treatment response or lack thereof in patients can enable an earlier switch to alternative treatment strategies that can enhance response rates. Here, Raman spectroscopy was applied to monitor early tumor biomolecular changes in sensitive (UM-SCC-22B) and resistant (UM-SCC-47) head and neck tumor xenografts for the first time in in vivo murine tumor models in response to radiation therapy. We used a validated multivariate curve resolution-alternating least-squares (MCR-ALS) model to resolve complex multicomponent Raman spectra into individual pure spectra and their respective contributions. We observed a significant radiation-induced increase in the contributions of lipid-like species (p = 0.0291) in the radiation-sensitive UM-SCC-22B tumors at 48 h following radiation compared to the nonradiated baseline (prior to commencing treatment). We also observed an increase in the contribution of collagen-like species in the radiation-resistant UM-SCC-47 tumors at 24 h following radiation compared to the nonradiated baseline (p = 0.0125). In addition to the in vivo analysis, we performed ex vivo confocal Raman microscopic imaging of frozen sections derived from the same tumors. A comparison of all control and treated tumors revealed similar trends in the contributions of lipid-like and collagen-like species in both in vivo and ex vivo measurements; however, when evaluated as a function of time, longitudinal trends in the scores of collagen-like and lipid-like components were not consistent between the two data sets, likely due to sample numbers and differences in sampling depth at which information is obtained. Nevertheless, this study demonstrates the potential of fiber-based Raman spectroscopy for identifying early tumor microenvironmental changes in response to clinical doses of radiation therapy.

Enhancing Patient Response to Patient-Reported Outcome Measures: Insights From a Leading Dutch University Hospital

ObjectivesEngaging patients with patient-reported outcome measures (PROMs) is a widely recognized and pressing challenge, yet our understanding of how to achieve this is limited. This study investigated strategies implemented by a Dutch university hospital aimed at enhancing response rates among outpatients from nearly 70 subdepartments. Response rates improved, but remained below desired levels. To deepen understanding and inform future strategies, we identified patient and consultation characteristics associated with response behavior. MethodsWe investigated strategies and their underlying rationales through a document analysis of internal hospital documentation (2020-2023) using the COM-B model. We exploited electronic health record data to identify patient and consultation characteristics associated with PROMs completion, estimating a multivariate logistic regression model (n = 46 468 outpatient consultations). ResultsThirteen strategies targeted outpatients’ capability, opportunity, and motivation to complete PROMs. In 2023, PROMs were completed in more than half of the 46 468 unique consultations (56%) for which a PROM was sent. Challenges persisted in establishing effective feedback mechanisms and accommodating non-Dutch-speaking patients. The multivariate analysis showed a significantly higher response among patients of high or middle socioeconomic status and those with an in-person consultation, ie, not using telehealth. Women, patients attending a follow-up visit, or those having their consultation on a Friday were slightly less likely to complete PROMs. ConclusionsResponse rates to PROMs improved but remained below desired levels, despite multiple strategies. Hospitals may benefit from effective patient feedback on PROMs and tailoring strategies to engage specific patient groups. These approaches can enhance successful implementation and promote equity in value-based healthcare.

Amplifying Influence: Unveiling the Dynamic Role of Speech and Language Therapists within ICPOP Specialist Community Teams across Ireland

Abstract Background Integrated Care Programme for Older People (ICPOP) provide services for people with complex needs requiring specialist community multidisciplinary assessment and intervention. This national programme aims to shift care from hospitals, toward communities. As of October 2023, 23 of 30 planned ICPOP teams have been established (Butler, 2023). The Irish Association for Speech and Language Therapists, recommend speech and language therapists (SLT) be included on all frailty intervention teams across all service areas, ensuring equal access regardless of geographical area. Currently 10 ICPOP teams have an SLT in post. The contribution of SLT within these teams remains unstudied. Understanding the role of SLTs within ICPOP, exploring similarities and differences, is essential for informing professional clinical guidelines and practice. Methods This study utilised an anonymous, non-experimental, cross-sectional survey design. The survey design incorporated the Tailored Research Method to enhance response rates. Survey Monkey (http://www.surveymonkey. com) was used to create and disseminate the open survey. All SLTs working on ICPOP teams were invited to participate. Results Findings highlight the diverse roles and responsibilities of SLTs within ICPOP. While some commonalities were observed in services provided by SLTs, such as dysphagia assessment and communication support, variations existed based on team location, setting, and individual professional experience. The majority of SLTs participated in non SLT specific activities such as triaging, conducting assessments and administrative duties. Rural SLTs faced challenges related to resources and coordination of care. Urban SLTs had greater access to specialist instrumental assessments. Conclusion This study underscores the importance of recognising and addressing the varied roles of SLTs within ICPOP teams to guide professional guidelines and promote consistency. By understanding the unique challenges and opportunities faced by SLTs in different geographical and organisational contexts, policymakers and healthcare leaders can better support professionals to meet the diverse needs of older individuals across Ireland.

Botulinum toxin for bruxism treatment: a nationwide study among oral and maxillofacial surgeons in Germany.

This study aimed to evaluate the use of botulinum toxin (BTX) for the treatment of bruxism in oral and maxillofacial surgery in Germany. A dynamic online questionnaire comprising 7 to 25 questions was formulated to gather general and specific information regarding using BTX to treat bruxism. The questionnaire underwent internal and external assessments for validation. Subsequently, it was distributed to 906 oral and maxillofacial surgeons (OMFS) affiliated with the German Association for Oral and Maxillofacial Surgery (DGMKG). Weekly reminders were dispatched over four weeks to enhance response rates. Participation in the study was voluntary and anonymized. Descriptive methods were employed for data analysis. 107 OMFS participated in the study, yielding a response rate of 11.81%. On average, 17 patients with bruxism were per month, with 4 of these patients receiving BTX therapy. BTX administration was frequently accompanied by splints and physiotherapy (35.51% of participants). Botox® (Allergan) was the preferred BTX preparation, utilized by 40.79% and reconstituted with saline by 92.11% of participants. The masseter muscles were primarily targeted for BTX treatment (67.57% of participants), averaging 29 BTX (Allergan-) units per side. Injection points for each masseter muscle typically amounted to six per side, preferred by 30.67% of participants. Follow-up assessments post-BTX treatment were conducted regularly, predominantly after four weeks, by 36% of participants. In 8% of cases, additional BTX injections were necessary due to inadequate outcomes. Side effects were reported in 4% of cases, commonly manifesting as a non-disturbing reduction in bite force. Most participating OMFS (61.84%) using BTX for bruxism therapy regarded bruxism treatment with BTX as evidence-based. Notably, 97.37% of respondents expressed their willingness to recommend BTX-based bruxism treatment to their colleagues. Overall, the efficacy of BTX therapy for bruxism was rated as good (53.95%) and very good (40.79%). The use of BTX for the management of bruxism among OMFS in Germany has demonstrated efficacy. Substantial variances in certain facets of bruxism treatment employing BTX have been observed. Additional research endeavors are warranted to comprehensively investigate distinct elements of BTX therapy for bruxism, including the optimal dosage of BTX units and the precise localization of injection sites across various muscles.

Enhancing Response Rates in Web-Based Surveys: The Impact of Direct Participant Contact.

Achieving a high participation rate is a common challenge in healthcare research based on web-based surveys. A study on local anesthetic systemic toxicity awareness and usage among medical practitioners at two Swiss university hospitals encountered resistance in obtaining personal email addresses from Heads of Departments. Participants were therefore divided into two groups: those who were directly invited via email (personal invitation group) and those who received a generic link through intermediaries (generic link group). The latter group was eventually excluded from survey data analysis. To determine whether one method of survey administration was more effective than another, we carried out a retrospective analysis of response rates and the proportion of new questionnaires completed after initial invitation and subsequent reminders. The results showed significantly higher response rates in the personal invitation group (40.2%, 313/779) compared to the generic link group (25.3%, 22/87), emphasizing the effectiveness of personal invitations on response rate (+14.9%, p = 0.007). The personal invitation group consistently yielded a higher number of completed questionnaires following the initial invitation and each reminder. The method of survey administration can greatly influence response rates and should be acknowledged as a quality criterion when conducting web-based surveys.

NSGO-OV-UMB1/ENGOT-OV30: A phase II study of durvalumab in combination with the anti-CD73 monoclonal antibody Oleclumab in patients with relapsed ovarian cancer

ObjectivesIn patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment. Here, we present the results from the NSGO-OV-UMB1/ENGOT-OV-30 trial evaluating the activity of combining the anti-CD73 antibody oleclumab with the anti-PD-L1 checkpoint inhibitor durvalumab in patients with recurrent EOC. MethodsIn this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors. ResultsThis trial included 25 patients with a median age of 66 years (47–77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2–4.2) and the median overall survival was 8.4 months (95% CI: 5.0–13.4). Infiltration of CD8+ cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR. ConclusionsCombined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC.

Determinants of pathological complete response and tumor regression in high-risk breast cancer treated with neoadjuvant radiotherapy and chemotherapy.

e12652 Background: Pathological complete response (pCR) is a recognized prognostic indicator in breast cancer patients undergoing neoadjuvant systemic therapy (naST). Known determinants of pCR include intrinsic subtype, proliferation index, grading, clinical tumor and nodal stage, as well as the type of systemic therapy. Incorporating neoadjuvant radiotherapy (naRT) may enhance response rates, disease-free survival, toxicity profiles, and cosmetic outcomes compared to adjuvant radiotherapy. However, the factors influencing pCR and primary tumor regression with the addition of neoadjuvant radiotherapy to chemotherapy are not well-documented. Methods: A retrospective analysis was conducted on 341 patients (cT1-cT4/cN0-N+) who received naRT and neoadjuvant chemotherapy between 1990 and 2003. Treatment included naRT to the breast and, in most cases, to the supra-/infraclavicular lymph nodes, complemented by an electron or brachytherapy boost. NaST was administered either sequentially or concurrently with RT, utilizing various regimens. Univariate and multivariate regression analyses were employed to evaluate the impact of different subgroups and treatment modalities on pCR (ypT0/Tis and ypN0) and complete primary tumor response (ypT0/Tis). Receiver operating characteristic (ROC) analysis assessed the interval between radiotherapy (RT) and surgical resection (Rx), as well as the radiotherapy dose. Results: Out of 341 analyzed patients, 31.1% achieved pCR. Multivariate analysis revealed that pCR rates were affected by the planned type of resection, breast cancer subtype, primary tumor stage, and the interval between radiation and surgery. The biologically effective dose to the tumor did not significantly impact pCR. Univariate analysis identified age, resection type, breast cancer subtype, clinical tumor stage, and grading as significant factors for primary tumor regression. In the multivariate analysis, resection type, subtype, and clinical tumor stage remained significant. Radiation dose to the tumor and the interval from radiation to surgery were not significant for pCR. However, a longer interval from radiotherapy to resection significantly predicted pCR when treatment factors were included in the model. Conclusions: The factors associated with pCR following combined neoadjuvant chemotherapy and radiotherapy are akin to those identified with neoadjuvant chemotherapy alone. A prolonged interval to surgery may be linked to higher pCR rates. Escalating the dose beyond 60 Gy did not lead to increased response rates.

First results of the NOGGO PERCEPTION: Phase II investigational study of pembrolizumab in combination with chemotherapy in platinum-sensitive recurrent low-grade serous ovarian cancer.

e17550 Background: Low-grade serous ovarian cancer (LGSOC), a rare ovarian malignancy, exhibits a very limited responsiveness to chemotherapy. There is a pressing need for new therapeutic combinations with modern agents to enhance response rates and prognosis in this patient subgroup. Immune checkpoint inhibitors offer a promising pathway, having shown effectiveness in various malignant diseases, including selected cases of ovarian cancer. If our trial should show pembrolizumab effectivity in LGSOC, it would be a signal and impulse for future clinical studies in this rare disease. Methods: This clinical trial is a multi-center, single-arm phase 2 study to evaluate pembrolizumab therapy concomitant to platinum-based chemotherapy (carboplatin plus pegylated liposomal doxorubicin & carboplatin plus gemcitabine) and as maintenance in recurrent LGSOC cases. Eligible for the trial are LGSOC patients with progression or recurrence at least six months after most previous platinum-containing therapy and in good general performance (ECOG 0/1). The primary objective is the 12 months progression free survival (PFS) rate. Secondary end-points include overall survival, response rate (RR), PFS and RR according to Ki67 expression levels, time to first subsequent therapy and its response, safety and quality of life. The trial is planned according to Simon’s two-stage design with total sample size up to 33 patients. The null hypothesis is PFS-rate of at least 12 months of 20%. During the first stage 18 patients were enrolled and since 5 patients showed PFS of 12 months the study has been continued within stage 2 to enrol additional 15 patients. The trial can be claimed as successful, if at least 11 patients show PFS after 12 months. Assuming a true PFS-rate of 40%, this trial has 5% type I error rate and 80% power. Results: Data from 18 patients enrolled into this trial from FPI up to the time of interim analysis have been analyzed. 5 patients had reached the primary endpoint. 6 patients progressed or died before they reached the primary endpoint. At this time, 10 patients are still undergoing treatment and 7 patients may still reach the primary endpoint. Patients have a median age of 60 years (range: 43-81), ECOG score of 0 was recorded in 16 patients (88.9%) and most received one prior line of chemotherapy (61.1%, range: 1-5). 14 patients (77.8%) received carboplatin + PLD and 4 patients (22.2%) received carboplatin + gemcitabine as chemotherapy. 10 patients (55.6%) had at least one SAE. 3 patients (16.7%) had at least one SAE with relation to study treatment. 1 SAE resulted in a fatal outcome but was assessed not be related to study treatment. Conclusions: The interim analysis showed positive results, strengthening the hypothesis that pembrolizumab is an effective agent capable of extending progression-free survival in the studied patient population. Clinical trial information: NCT04575961 .

The Role of Metabolic Reprogramming in the Tumor Immune Microenvironment: Mechanisms and Opportunities for Immunotherapy in Hepatocellular Carcinoma.

As one of the emerging hallmarks of tumorigenesis and tumor progression, metabolic remodeling is common in the tumor microenvironment. Hepatocellular carcinoma (HCC) is the third leading cause of global tumor-related mortality, causing a series of metabolic alterations in response to nutrient availability and consumption to fulfill the demands of biosynthesis and carcinogenesis. Despite the efficacy of immunotherapy in treating HCC, the response rate remains unsatisfactory. Recently, research has focused on metabolic reprogramming and its effects on the immune state of the tumor microenvironment, and immune response rate. In this review, we delineate the metabolic reprogramming observed in HCC and its influence on the tumor immune microenvironment. We discuss strategies aimed at enhancing response rates and overcoming immune resistance through metabolic interventions, focusing on targeting glucose, lipid, or amino acid metabolism, as well as systemic regulation.

Abstract 5552: Uncovering clinically significant tumor microenvironment interaction programs across diverse cancers

Abstract Background: Cell-cell interactions (CCI) within the tumor microenvironment (TME) play pivotal roles in various tumor behaviors, including cancer growth, metastasis, immune evasion, and resistance to therapy. Compared to front-line treatments, targeting specific CCIs marks a paradigm shift in cancer therapy, aiming for enhanced response rates with reduced side effects. Although current approaches targeting immune regulation pathways exhibit effective anti-tumor responses, substantial variability in response rates across patients and cancer types persists. Consequently, a critical imperative emerges to discover novel interaction programs (IPs) across diverse TMEs, demonstrating clear clinical impact across a broad spectrum of patients. Methods: Characterization of pan cancer IPs. We compiled a pan cancer single-cell RNA-seq (scRNA-seq) atlas, including 4 million cells from 890 tumors across 14 cancer types. In each sample, CCIs were inferred using a ligand-receptor (LR) analysis framework, generating ranked CCI scores based on consensus from various LR inference methods. To find IPs enriched across TMEs, we applied an unsupervised factorization approach. The outcome represents CCIs as factors, where sample loading indicates factors’ strength, and feature loading highlights the cells and LR pairs constituting each IP. Evaluating IPs in clinical RNA-seq cohorts. Given the more immediate translational potential of bulk cancer sequencing for patient stratification, we devised an approach to predict IPs' strengths in bulk RNA-seq. Random Forest regression models using pseudo-bulk expression of cancer genes were trained to predict the loading (strength) of factors (IPs) in each sample in the scRNA-seq pan-cancer atlas. These models were subsequently applied to cancer samples in The Cancer Genome Atlas (TCGA) cohort to assess the clinical impact of various IPs on patient mortality. Results: We assessed the impact of IPs on 5-year overall survival using Cox proportional hazard models. We identified multiple factors significantly associated with survival in at least 4 cancer types. Notably, a robust prognostic factor linked to the inclusion of anti-tumor natural killer cell interactions and exclusion of pro-tumor macrophage interactions was found in MESO, LGG, ACC, and UVM (HR 1.6-6.6, p < 0.05). The validation of IPs using spatial transcriptomics and evaluation of IP prediction's utility in targeted treatment cohorts are currently underway. Conclusion: We highlight a potent method for detecting clinically significant IPs involving cells in TME communicating through LR pairs. The ability to assess these scRNA-seq-derived IPs in clinical bulk RNA-seq cohorts signifies a valuable advancement. Our approach holds promise for expanding the repertoire of cell therapies, identifying new treatment targets, and improving our predictive capabilities for responses to existing therapies. Citation Format: Ido Nofech-Mozes, Vivian Wang, Philip Awadalla, Sagi Abelson. Uncovering clinically significant tumor microenvironment interaction programs across diverse cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5552.

Abstract 6645: Temporal immune profiling reveals systemic anti tumor immunity in triple negative breast cancer(TNBC) patients treated with immunotherapy and radiation

Abstract Combining pembrolizumab (anti-PD1) with radiation therapy (RT) has shown to enhance response rates in TNBC. We hypothesize that this improved efficacy is not just localized to the tumor bed, but also involves a broader systemic immune response, although the precise mechanisms are yet to be fully understood. Therefore, in this study, we aimed to investigate T cell clonal dynamics in Tumor and peripheral blood mononuclear cells (PBMCs) in 9 patients (6 responders(R) and 3 non-responders (NR)) from 3 different timepoints (before therapy (Baseline), after anti-PD1 alone and after anti-PD1+RT). CD45+ positive stained cells were sorted for subsequent single-cell RNA and T-cell receptor (TCR) sequencing analysis.Through single-cell analysis, we identified increased proportions of exhausted CD8+ and Treg cells from baseline to both treatment points, whereas exhaustedCD4+ T cells increased in proportions after PD1 alone in Responders. We aimed to then understand the origin of these cells, and how they might contribute to systemic immunity. Hence, by TCR overlap between Tumor and PBMC’s we detected 590 overlapped clones in CD8 and 1000 overlapped clones in CD4 T cells. Neo-TCR score was higher in these overlapped clones, suggesting tumor reactive clones can be identified in PBMC’s. Compared to exhausted CD4, exhausted CD8 T cell and Treg had higher overlapped clones between Tumor and PBMC. We also found that exhausted CD8+T cells clonal expansion after treatment was higher in pre-existing clones, compared to new clones in Responders. These pre-existing clones consisted of overlapped clones, suggesting tumor reactivity to be present in PBMC’s before treatment. Further investigation suggested that exhausted CD8+ cells also showed increased transition to TEMRA (in PBMC) and a tissue-resident memory CD8 T cell subset, under combination therapy. This pattern was not seen in exhausted CD4+Tcells or Treg cells, indicating that CD8+ T cell subsets in the blood are crucial in driving systemic anti-tumor immunity. Overall, this study has identified the systemic immune response triggered by the combination of anti-PD1 and radiation therapy highlighting its potential to inform and refine future therapeutic strategies in TNBC treatment. Citation Format: Vaishnavi Devarakonda, Jolene Viramontes, Satchel Stevens, Tahir Dar, Emily Ko, Elvin Canesco, Kaiden Anderson, Jlenia Guarnerio, Simon Knott, Stephen L. Shiao. Temporal immune profiling reveals systemic anti tumor immunity in triple negative breast cancer(TNBC) patients treated with immunotherapy and radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6645.

Association between resting-state connectivity patterns in the defensive system network and treatment response in spider phobia—a replication approach

Although highly effective on average, exposure-based treatments do not work equally well for all patients with anxiety disorders. The identification of pre-treatment response-predicting patient characteristics may enable patient stratification. Preliminary research highlights the relevance of inhibitory fronto-limbic networks as such. We aimed to identify pre-treatment neural signatures differing between exposure treatment responders and non-responders in spider phobia and to validate results through rigorous replication. Data of a bi-centric intervention study comprised clinical phenotyping and pre-treatment resting-state functional connectivity (rsFC) data of n = 79 patients with spider phobia (discovery sample) and n = 69 patients (replication sample). RsFC data analyses were accomplished using the Matlab-based CONN-toolbox with harmonized analyses protocols at both sites. Treatment response was defined by a reduction of >30% symptom severity from pre- to post-treatment (Spider Phobia Questionnaire Score, primary outcome). Secondary outcome was defined by a reduction of >50% in a Behavioral Avoidance Test (BAT). Mean within-session fear reduction functioned as a process measure for exposure. Compared to non-responders and pre-treatment, results in the discovery sample seemed to indicate that responders exhibited stronger negative connectivity between frontal and limbic structures and were characterized by heightened connectivity between the amygdala and ventral visual pathway regions. Patients exhibiting high within-session fear reduction showed stronger excitatory connectivity within the prefrontal cortex than patients with low within-session fear reduction. Whereas these results could be replicated by another team using the same data (cross-team replication), cross-site replication of the discovery sample findings in the independent replication sample was unsuccessful. Results seem to support negative fronto-limbic connectivity as promising ingredient to enhance response rates in specific phobia but lack sufficient replication. Further research is needed to obtain a valid basis for clinical decision-making and the development of individually tailored treatment options. Notably, future studies should regularly include replication approaches in their protocols.

Current opinion on large-scale prospective myomectomy databases toward evidence-based preconception and antenatal counselling utilising a standardised myomectomy operation note.

No large-scale databases exist of pregnancy outcomes and rate of uterine rupture for women after myomectomy, resulting in inconsistent antenatal counselling and decision-making regarding mode and timing of delivery. Standardising information collected at myomectomy may facilitate data collection, informing prenatal/ antenatal counselling. To determine clinician opinions regarding standardisation of myomectomy operation notes to allow comprehensive data input into a prospective database of pregnancy outcomes, toward an evidence-based approach to decision making regarding timing and mode of delivery in subsequent pregnancies. A google forms survey was emailed to all consultant (attending-level) obstetricians and gynaecologists across 25 hospitals in London, Kent, Surrey, and Sussex (UK) between March and May 2022. To enhance response rates, two further email reminders were sent alongside in-person reminders from selected local unit representatives. Senior clinician opinion for characteristics necessary to collect at time of surgery to develop a widescale database of post myomectomy pregnancy outcomes. 209/475 (44%) responses received; 95% (198/209) agreed with standardising operation notes. Criteria selected for inclusion included cavity breach (98%, 194/198), location (98%, 194/198), number of fibroids removed (93%, 185/198) and number of uterine incisions (96%, 190/198). Gynaecologists support standardising myomectomy operation notes to inform the development of prospective large-scale databases of pregnancy outcomes after myomectomy. Acquisition of clinician opinions on the development and content of a standardised myomectomy operation note to aid the development of a pregnancy-outcome database for women after myomectomy.

Novel two-dimensional conductive metal–organic framework-based heterostructures for high-performance electro-ionic soft actuators

Current artificial muscle technology necessitates a significant technological advancement to increase bending strain, enhance response rates, and prolong stability while ensuring consistent and reliable performance across various stimuli.

Optimizing Web Surveys in Research: Methodological Considerations and Validity Aspects

Web surveys are a data collection method where surveys or questionnaires are sent over the internet to a sample of respondents, and they can respond to this survey over the World Wide Web. Web surveys have become increasingly prevalent in research due to their convenience, cost-effectiveness, and broad reach. However, ensuring web surveys’ methodological rigor and validity is crucial for generating reliable findings. This paper presents a comprehensive examination of methodological considerations and validity concerns in web surveys, aiming to optimize their effectiveness and enhance the quality of research outcomes. Methodological aspects such as survey design, question formulation, sampling techniques, and data collection procedures are explored, emphasizing the need for best practices and guidelines. A standardized close-ended questionnaire was distributed to researchers conducting web surveys to collect data. A random distribution was used to get a sample size of 200 questionnaires, of which 170 were successfully collected. However, by eliminating the incomplete data, 150 replies were received, indicating a response rate of 85%. In order to achieve this objective, this study employed Structural Equation Modelling (SEM) to analyze the data that was collected from participants who utilized web surveys in their research studies. The results revealed that methodological aspects of web surveys significantly enhance reliability and validity, reduce challenges and biases associated with web surveys, and optimize their effectiveness. Furthermore, the results confirmed that reliability and validity and challenges and biases associated with web surveys fully mediate the relationship between methodological aspects of web surveys and the optimization of their effectiveness. Researchers can deliberately improve participant engagement and enhance response rates and data quality by prioritizing methodological concerns and validity. Personalized survey invites, gamification or interactive aspects, smooth mobile compatibility, and well-structured incentives are essential to strengthen participant interest and commitment. Furthermore, the implementation of rigorous data quality protocols, including validation procedures and attention prompts, plays a crucial role in upholding the integrity of the gathered data. Researchers can strategically enhance participant engagement by focusing on methodological considerations and validity to bolster response rates and data quality. Implementing personalized survey invitations, integrating gamification or interactive elements, ensuring seamless mobile compatibility, and offering well-structured incentives collectively foster participant interest and commitment. Additionally, diligent data quality measures, such as validation checks and attention prompts, contribute to the integrity of collected information. By addressing these issues and advancing the understanding of web survey methodologies, researchers can optimize the validity and reliability of their findings, strengthening the overall quality of web survey research.

Efficacy of bevacizumab combined with apatinib in the treatment of advanced metastatic gastric cancer.

To evaluate the clinical efficacy and safety of bevacizumab combined with apatinib in the treatment of advanced metastatic gastric cancer, providing insights for treatment decisions. We conducted a single-center retrospective study involving patients with metastatic gastric cancer treated with apatinib, with or without bevacizumab, between August 2018 and April 2021 at Nanchang Medical College. Data on efficacy, adverse events, response rates, and quality of life were collected and compared. No significant differences were observed in complete remission, partial response, stable disease, disease progression, objective response rate, or disease control rate between the groups (all P>0.05). The median progression-free survival was 9.23 months in the control group and 9.94 months in the observation group (P=0.587). Median overall survival (OS) was 19.64 months in the control group and 26.44 months in the observation group (P=0.187). Univariate and multivariate analyses identified combination therapy with apatinib and bevacizumab, primary lesion resection, and number of metastatic organs as independent prognostic factors for OS. Scores for role, emotional, somatic, cognitive, and social functions were significantly higher in the observation group post-intervention (all P<0.05). In patients with advanced metastatic gastric cancer, combined therapy with bevacizumab and apatinib significantly improved OS, enhanced response rates, and increased rates of early and maximal tumor shrinkage.

IL4I1: a novel molecular biomarker represents an inflamed tumor microenvironment and precisely predicts the molecular subtype and immunotherapy response of bladder cancer.

Introduction: IL4I1, also known as Interleukin-4-induced gene 1, is an enzyme that can modulate the immune system by acting as a L-amino acid oxidase. Nevertheless, a precise understanding of the correlation of IL4I1 with immunological features and immunotherapy efficacy in bladder cancer (BLCA) remains incomplete. Methods: We analyzed RNA sequencing data from the Cancer Genome Atlas (TCGA) to investigate the immune function and prognostic importance of IL4I1 across different cancer types. We further examined the TCGA-BLCA cohort for correlations between IL4I1 and various immunological characteristics of tumor microenvironment (TME), such as cancer immune cycle, immune cell infiltration, immune checkpoint expression and T cell inflamed score. Validation was conducted using two independent cohort, GSE48075 and E-MTAB-4321. Finally, RNA sequencing data from the IMvigor210 cohort and immunohistochemistry assays were employed to validate the predictive value of IL4I1 for the TME and immunotherapy efficacy. Results: In our findings, a positive correlation was observed between IL4I1 expression and immunomodulators expression, immune cell infiltration, the cancer immune cycle, and T cell inflamed score in BLCA, suggesting a significant link to the inflamed TME. In addition, studies have shown that IL4I1 elevated levels of individuals tend to be more performance for basal subtype and exhibit enhanced response rates to diverse treatment modalities, specifically immunotherapy. Clinical data from the IMvigor 210 cohort confirmed a higher rate of response to immunotherapy and better survival benefits in patients with high IL4I1 expression. Discussion: To summarize, our research showed that elevated IL4I1 levels are indicative of an inflamed TME, the basal subtype, and a more favorable response to various treatment methods, especially immune checkpoint blockade therapy in BLCA.

All Roads Lead to Rome: YAP/TAZ Activity Influences Efficacy of KRASG12C Inhibitors

AbstractThe development of direct inhibitors of KRASG12C represents a monumental step forward in the field of oncology. Nevertheless, there is considerable opportunity to enhance response rates to KRASG12C inhibitors. In this issue of Cancer Research, three investigative teams explore the modulation of KRASG12C inhibitor activity in lung, colorectal, and pancreatic cancers using CRISPR-based knockout screens. While each group identified and validated a variety of genes and pathways conferring resistance to KRASG12C inhibition, all three groups converged upon activation of YAP/TAZ as a common means of resistance. While coinhibition of KRASG12C and YAP/TAZ did not cause complete tumor regression in xenograft models, combining YAP/TAZ inhibition was capable of significantly extending the response of tumors to KRASG12C inhibition.See related articles by Mukhopadhyay et al., p. 4095, Edwards et al., p. 4112, and Prahallad et al., p. 4130