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Unlocking the Potential of Isatin Scaffolds in Acetylcholinesterase Inhibition.2 weeks agoThe therapeutic significance of acetylcholinesterase (AChE) inhibition is most prominently observed in the management of various neurodegenerative and neuromuscular disorders, including Alzheimer's disease (AD), and myasthenia gravis (MG). The present review examines isatin-based compounds as a promising class of drugs for treating these conditions, focusing on their ability to inhibit AChE. While AD is characterized by a significant loss of cholinergic neurons leading to a deficiency in acetylcholine (ACh), MG is an autoimmune disease where the body produces antibodies that block or destroy ACh receptors at the neuromuscular junction. By inhibiting AChE, therapeutic agents increase the availability of ACh, thereby enhancing cholinergic neurotransmission and improving muscle strength or cognitive function. The underlying issue in MG is the reduced number of functional receptors rather than a primary decrease in AChE production. However, inhibition of the enzyme remains a vital strategy for symptom management. Accordingly, this review provides a systematic overview of the various synthetic strategies reported in the literature over the last decade for enhancing isatin-based AChE inhibitory activity. These strategies include modifications of the isatin nitrogen, such as N-alkylation, N-acylation, or N-arylation. Another strategy is aromatic ring substitution, where various substituents (e.g., halogens, nitro, amino, and alkyl groups) are introduced typically at the C5, C6, and/or C7 positions. C3-carbonyl functionalization is also reported, exemplified by the formation of Schiff bases, hydrazones, or spirocyclic derivatives. Our findings highlight the exceptional potential and adaptability of isatin derivatives in medicinal chemistry, highlighting the major advances within the last 10 years and the future directions.CancerAccess
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Accuracy and Safety of Large Language Models in Endometrial Cancer Decision Making: A Case-Based In Silico Benchmarking Study.2 weeks agoTo compare the concordance of ChatGPT, Gemini, and Claude with a prespecified expert guideline-based reference standard in fabricated endometrial cancer clinical vignettes under standardized prompting.
We conducted a case-based in silico benchmarking study using 35 fabricated postoperative endometrial cancer vignettes representing a broad spectrum of ESGO-ESTRO-ESP 2025 management scenarios. Each vignette was submitted to ChatGPT, Gemini, and Claude in independent chat sessions using the same standardized prompt. The primary end point was concordance with the prespecified expert reference standard, scored as 0 (discordant), 1 (partially concordant), or 2 (fully concordant). Secondary end points were major safety issues and recognition of missing critical information. A post hoc subgroup analysis evaluated the effect of guideline-informed prompting in 12 cases.
Concordance differed significantly across models (P < .001). Gemini achieved the highest performance, with a median concordance score of 2 (IQR 1-2), compared with 1 (IQR 0-1) for ChatGPT and 0 (IQR 0-1) for Claude. Fully concordant recommendations were generated in 65.7% of cases by Gemini, 2.9% by ChatGPT, and 8.6% by Claude. Major safety issues also differed across models (P = .007), occurring in 22.9% of Gemini responses, 48.6% of ChatGPT responses, and 54.3% of Claude responses. In the subset of vignettes with intentionally missing decisive information, Gemini identified the need for additional data in 83.3% of cases, compared with 50.0% for both ChatGPT and Claude. In the post hoc subgroup analysis, guideline-informed prompting significantly improved concordance for Gemini and Claude.
Mainstream consumer large language models showed substantially different performance in postoperative endometrial cancer decision making. Although Gemini achieved higher concordance and fewer major safety issues than ChatGPT and Claude, no model demonstrated performance sufficient to support autonomous clinical use in multidisciplinary management.CancerAccessCare/Management -
Beta Testing an mHealth Symptom Management Intervention for People With Advanced Cancer: Single-Cohort Feasibility and Acceptability Study.2 weeks agoPeople living with advanced cancer experience more frequent and severe symptoms than those with early-stage disease. Common, distressing symptoms include sleep difficulties, worry and uncertainty, fatigue, and depression. Cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) effectively manage these symptoms but are often too time intensive for patients with multiple appointments, limited energy, and competing priorities. Brief, mobile health (mHealth) interventions provide an accessible alternative, particularly for rural patients with limited access to palliative or psychosocial oncology services.
Building on our successful in-person and Digital Video Disk-based pilot trial of a 3-session, integrated CBT-ACT symptom management intervention for patients with advanced cancer, Finding Our Center Under Stress (FOCUS), the current study evaluated the feasibility and acceptability of a 4-session mHealth version.
In this single-cohort feasibility and acceptability study, people with advanced cancer were recruited from hospital-based oncology clinics representing 4 cancer types (breast, melanoma, multiple myeloma, and prostate). Baseline assessments included sociodemographic data, patient-reported outcomes for sleep (Insomnia Severity Index), anxiety (7-item Generalized Anxiety Disorder scale and Penn State Worry Questionnaire), fatigue (Fatigue Symptom Inventory), depression (Center for Epidemiological Studies Depression Scale), and a 7-day sleep diary completed in the app. Participants then completed 4 modules addressing sleep difficulties, worry and uncertainty, fatigue, and depression. Primary outcomes were feasibility and acceptability. Feasibility benchmarks included recruitment (50% enrollment), retention (70%), and app completion (50%). After 6 weeks, participants completed the Internet Evaluation and Utility Questionnaire, and a subset completed qualitative interviews about their experience with the FOCUS app. We report quantitative and qualitative findings and lessons learned from app development.
Overall, 64.7% (11/17) of the approached patients enrolled, and 70% (7/10) completed more than half of the app. Participants rated FOCUS highly for ease of understanding (mean 3.83/4, SD 0.41), convenience (mean 3.67/4, SD 0.82), and utility (mean 3.33/4, SD 0.82). All participants would recommend the app to others and would use it again for future problems. Favorite components included patient videos and the Sleep and Worry and Uncertainty Modules. Suggested improvements included video quality (lighting and sound), sleep diary usability, and additional professional guidance.
The FOCUS intervention was successfully delivered via mobile technology and demonstrated feasibility and acceptability in beta testing. The FOCUS mHealth app offers an evidence-based, accessible symptom management intervention for people with advanced cancer, particularly in rural communities. Guided by participant feedback, FOCUS 2.0 will enhance video segments, add telehealth support, and expand interactive and motivational features. A randomized controlled trial will evaluate its effectiveness.CancerAccessAdvocacyEducation -
Molecular profiling of apoptotic, inflammatory, and angiogenic markers in prostate cancer: Focus on p53, IL-6, IL-8, Bax/Bcl-2 ratio, and VEGF.2 weeks agoAim: To perform a comprehensive molecular profiling of key apoptotic, inflammatory, and angiogenic markers - p53, IL-6, IL-8, Bax/Bcl-2 ratio, and VEGF -in peripheral blood samples of patients with prostate cancer.
Materials and Methods: A total of 60 male participants were enrolled in the study, comprising 40 patients with histologically confirmed prostate cancer and 20 age-matched healthy controls. The median age in both groups was 68 years (range: 55-78). Patients were stratified according to Gleason score, PSA levels, and tumor stage from the begging of August 2024 to the end May 2025. Blood samples from patients suffering Prostate cancer (PCa). ELISA Human-specific ELISA kits (e.g., from R&D Systems, BioLegend, or Abcam) (from Serum) for IL-6, IL-8, VEGF. As well as Bax/Bcl-2 Ratio. RNA Quality Check: The concentration and integrity of RNA will be evaluated using a NanoDrop agarose gel. cDNA Synthesis: A reverse transcription kit (such as Thermo Fisher's High-Capacity cDNA Reverse Transcription Kit) will be used to create cDNA from 1 μg of RNA. Target Genes p53, Primers, and Probes for Quantitative Real-Time PCR (qRT-PCR).
Results: p53 Expression, qPCR analysis revealed significantly decreased expression of p53 mRNA in prostate cancer patients compared to controls (mean ΔCt = 6.1 ± 0.8 vs. 4.3 ± 0.6; p < 0.001. Serum IL-6 levels (by ELISA) were elevated in prostate cancer patients (mean = 18.4 ± 6.2 pg/mL) compared to controls (7.1 ± 2.3 pg/mL); p < 0.001. Similarly, IL-8 levels were significantly higher in patients (27.5 ± 9.8 pg/mL) than in controls (10.2 ± 3.5 pg/mL); p < 0.001. Serum VEGF concentrations were significantly increased in prostate cancer patients (median = 296 pg/mL; IQR = 230-360 pg/mL) compared to controls (median = 122 pg/mL; IQR = 90-160 pg/mL); p < 0.0001.
Conclusions: Prostate cancer patients exhibited decreased p53 and Bax/Bcl-2 ratio, indicating impaired apoptosis. IL-6 and IL-8 were significantly elevated and positively correlated, reflecting a pro-inflammatory environment.CancerAccessAdvocacy -
Correlation of serum tumor markers (CEA and CA15-3) with clinicopathological features in breast cancer patients in Iraq.2 weeks agoAim: This research is aimed at looking into the relationship between the levels of the markers and the clinicopathological features of breast cancer patients in Iraq.
Materials and Methods: The study population consisted of 150 breast cancer patients in a cross-sectional correlation study. Demographic, clinical, and pathological data were collected including molecular subtypes, tumor staging and grading. The serum levels of CEA and CA15-3 were determined and the results correlated with patient characteristics. The statistical methods employed were ANOVA, t-tests, and Pearson correlation.
Results: Out of the total patients, 98.5% were females, 52.9% were over 50 years of age and 79.6% were married. The Luminal types were the most frequent (The Luminal types were the most frequent (Luminal A: 45.3%, Luminal B: 36.5%) while the triple-negative (10.1%) and HER2-positive (8.1%) subtypes were the least common. There was an increase in serum levels of CEA and CA15-3 in advanced tumor stage and high grade cancer, a significant difference in CA15-3 levels between the age groups (p=0.010). The marker levels varied according to the molecular subtypes with Luminal A demonstrating a greater CEA and Luminal B showing a higher CA15-3.
Conclusions: The levels of serum CEA and CA15-3 are indicative of the breast cancer patients' tumor stage, grade, and molecular subtype. The regular monitoring of these markers may provide better understanding of the disease progress and help in the formulation of patient-specific management plans.CancerAccessCare/ManagementAdvocacy -
Correlation between interleukin-17 levels and oral manifestations in patients with oral squamous cell carcinoma.2 weeks agoAim: To assess the level of salivary IL-17 in Oral Squamous Cell Carcinoma patients compared to healthy individuals and their association with molecular etiology and oral manifestations.
Materials and Methods: A case-control study was carried out in 56 patients with OSCC and 46 healthy matched subjects. The demographics, tumor molecular profiles (TP53 mutations and EGFR overexpression), and oral examination findings were systematically recorded. ELISA was used to detect the concentration of IL-17 in saliva.
Results: Salivary IL-17 levels were significantly elevated in patients with Oral Squamous Cell Carcinoma (21.34 ± 4.6 pg/mL) compared to the control group (19.72 ± 4.2 pg/mL, p = 0.040). IL-17 was higher in TILs of those patients; tumors with overexpression of EGFR exhibited higher levels than those with TP53 mutations. The most common oral manifestations observed in this study included mucositis and xerostomia. The increase in salivary IL-17 was also found to be independently associated with mucosal alterations and changes in pigmentation.
Conclusions: Salivary IL-17 levels were elevated in patients with Oral Squamous Cell Carcinoma, with this biomarker being correlated in such cases with tumors driven by EGFR and with specific oral manifestations. Thus, this biomarker has the potential to be a non-invasive tool for disease detection and follow-up.CancerAccessAdvocacy -
Renal-clearable fluorescent probe for early detection of pancreatic cancer in living murine models.2 weeks agoPancreatic cancer (PC) is a highly aggressive and lethal malignancy with extremely poor patient survival rates. The lack of biomarkers and deep tissue detection barriers has presented long-standing and unsolved issues, severely hindering the early diagnosis of PC even in living rodent models. Here, we report a renal-clearable leucine aminopeptidase (LAP)-activatable fluorescence probe, overturning the probe's pharmacokinetics from the liver to kidney pathway (90% of the injection dosage). This strategy reduces interference in the liver and enables LAP as a biomarker for PC detection in murine models. After in situ response with LAP in the pancreas, renal-clearable fluorogenic fragments could be efficiently excreted into the urine, thus addressing the depth barriers of PC. Our strategy has resolved the lack of biomarkers and deep tissue detection barriers in early PC detection in murine models, which would greatly expand the bioanalytical toolbox for PC identification, further enabling the efficient screening of PC drugs at the animal level and the exploration of diagnostic methods for PC.CancerAccess
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Comparative evaluation of ChatGPT and gemini responses to patient-oriented questions on breast cancer.2 weeks agoBreast cancer, the most common malignancy among women, remains a major global public health concern. With the rapid growth of artificial intelligence-based language models, it is essential to evaluate their potential roles in patient education. This study compared ChatGPT and Gemini in responding to patient-oriented questions about breast cancer and its surgical treatment regarding scientific accuracy, clarity, and unnecessary detail.
Forty frequently asked questions were collected from Turkish online sources. Both models were queried under identical conditions on August 13, 2025, and the responses were anonymized for blinded evaluation. Four general surgeons experienced in breast surgery independently assessed each response using a five-point Likert scale across three domains: scientific accuracy, clarity, and unnecessary detail.
Response lengths were recorded and compared. ChatGPT achieved significantly higher median scores than Gemini in scientific accuracy [4.75 (3.50-5.00) vs. 4.25 (3.50-5.00); p < 0.001], clarity [4.75 (3.50-5.00) vs. 4.25 (3.25-5.00); p = 0.005], and unnecessary detail [5.00 (5.00-5.00) vs. 4.50 (3.50-5.00); p < 0.001]. The overall median score was 4.83 (4.08-5.00) for ChatGPT and 4.33 (3.50-4.92) for Gemini (p < 0.001). Gemini's responses were significantly longer (244 ± 84 vs. 170 ± 47 words; p < 0.001).
Both models demonstrated acceptable overall performance. However, ChatGPT's higher scores and shorter, more focused responses indicate that it may be a more efficient tool for addressing breast cancer-related patient questions. In their current form, these models should not be used for diagnostic or clinical decision-making purposes. AI-generated health information should be used only under expert supervision and for educational or supportive purposes.CancerAccessCare/ManagementAdvocacyEducation -
Characterizing the Objective Time Spent on Health Care Activities in Clinic and at Home for Patients With Cancer.2 weeks agoWhile the time burden of cancer care is increasingly recognized in oncology, existing research lacks the granularity needed to identify intervention targets. This study characterized time spent on cancer care at home and in-clinic, including travel, waiting, and clinical tasks, assessing variations by treatment modality.
We conducted a secondary analysis of two longitudinal cohorts. Cohort 1 included patients with metastatic breast or advanced ovarian cancer (n = 55) and Cohort 2 included patients with any cancer (n = 55) receiving systemic anti-cancer therapy. Participants used a mobile application for 28 days that collected GPS and motion sensor data to infer locations. Daily surveys characterized activities and captured time spent on home-based tasks.
The study population (N = 110) was predominantly female and White, receiving a mix of infusion and oral treatments. Participants recorded 597 out-of-home healthcare episodes. While median time receiving care per episode for lab-only visits was short (10 min), visits combining labs and treatment had a median duration of 162 min (compared to treatment alone, median duration of 68 min). Patients on infusion therapies experienced higher time burdens per episode both in-facility (median 125 min vs. 50 min for oral therapy) and at home for scheduling and symptom management (median 188 min vs. 102 min).
Patients face substantial time burdens that extend beyond the clinical encounter. Waiting between stages, such as labs and treatment, makes combined out-of-home healthcare episodes disproportionately time-consuming. These data facilitate a deeper understanding of the trade-offs between different treatment modalities and care delivery models.CancerAccessCare/ManagementAdvocacy -
Respiratory Syncytial Virus-Associated Disease in Children Receiving Intensive Care.2 weeks agoData defining respiratory syncytial virus (RSV)-associated critical illness, risk factors, and outcomes among older children and adolescents are limited. As RSV prevention options expand, improved characterization of RSV-associated disease burden across childhood is needed.
To quantify RSV-associated intensive care unit (ICU) admissions and mortality among children aged 2 to 17 years and evaluate associations between pediatric complex chronic conditions (CCCs) and mortality.
This retrospective, multicenter cohort study was performed from January 1, 2017, to June 1, 2023, among children aged 2 to 17 years admitted to ICUs. Data were analyzed from January to March 2026.
RSV identified by laboratory testing or diagnosis codes.
Primary outcome was hospital mortality. Bivariate associations between mortality and covariates were calculated, and multivariable logistic regression was used to identify variables associated with mortality.
This study included 6430 RSV-associated ICU admissions for children aged 2 to 17 years (8.3% of 77 395 ICU admissions; median [IQR] age, 6.6 [3.4-12.6] years; 3457 [53.8%] male). The median (IQR) ICU length of stay was 2.9 (1.5-6.8) days, and the median (IQR) hospital LOS was 5.9 (3.0-14.3) days. Positive pressure ventilation was used in 2061 admissions (32.0%), vasoactive agents in 1788 (27.8%), and both in 903 (14.0%). Hospital mortality occurred in 484 admissions (7.5%) and accounted for 484 of 735 RSV-associated deaths (65.9%) across all ages. At least 1 CCC category was present in 3680 admissions (57.2%) and 454 of 484 deaths (93.8%); 3 or more CCC categories were present in 1666 admissions (25.9%) and 332 of 484 deaths (68.6%). Higher CCC burden was associated with mortality, particularly with 3 or more CCCs (mortality odds ratio [MOR 22.56; 95% CI, 15.44-32.97). CCC burden was associated with older age but remained associated with mortality across age strata. In adjusted analyses, malignant neoplasm (adjusted MOR ([aAMOR), 4.27 [95% CI, 3.16-5.77]), neurologic or neuromuscular (aAMOR, 2.66 [95% CI, 2.08-3.39]), respiratory (aAMOR, 2.36 [95% CI, 1.83-3.03]), transplant (aAMOR, 2.18 [95% CI, 1.47-3.23]), congenital or genetic, metabolic, and cardiovascular disease as well as technology dependence remained associated with mortality.
In this cohort study of 6430 RSV-associated ICU admissions among children aged 2 to 17 years, older children and adolescents represented a substantial proportion of severe RSV-associated disease and mortality; deaths were concentrated among children with CCCs. These results suggest that high-risk pediatric subpopulations may benefit from RSV prevention.CancerCardiovascular diseasesAccessCare/ManagementAdvocacy