Low vitamin D levels during pregnancy are associated with an increased risk of Gestational Diabetes Mellitus (GDM), potentially mediated by altered vitamin D metabolism. Cytochrome P450 family 24 subfamily A member 1 (CYP24A1) plays a key role in vitamin D catabolism, but its epigenetic regulation in GDM remains unclear.

This cross-sectional study included 150 pregnant women [normoglycemic (NGDM, n = 50), early GDM (eGDM, n = 50), and GDM (n = 50)] and 40 placental samples (NGDM, n = 20; GDM, n = 20). Gene expression of histone deacetylases (HDACs), sirtuins (SIRTs), and CYP24A1 was analyzed using real-time PCR. In vitro experiments using BeWo cells assessed the effects of high glucose and trichostatin A (TSA).

CYP24A1 expression was significantly increased in GDM participants. Distinct alterations in HDAC and SIRT expression were observed, with HDAC3, HDAC4, and HDAC7 negatively correlated and SIRT7 positively correlated with CYP24A1. HDAC modulation using TSA regulated CYP24A1 expression under hyperglycemic conditions.

These findings offer insights into the association of multiple HDACs regulating CYP24A1-mediated vitamin D deficiency in the pathophysiology of GDM. However, further mechanistic and longitudinal studies are required to elucidate the precise mechanism.

To quantitatively assess parental engagement, perceptions, and decision-making attitudes toward fluorescence-guided surgery (FGS) in pediatric solid tumors.

A structured questionnaire was administered to caregivers of children with Beckwith-Wiedemann syndrome in collaboration with the "Associazione Italiana Sindrome di Beckwith-Wiedemann", facilitating outreach to families within the national support network. Emotional responses (optimism, hope, confidence, anxiety, worry, and uncertainty) and perceived support were assessed using 5-point Likert scales (1 = not at all, 5 = extremely). The survey also explored prior awareness of FGS, perceived impact on surgical outcomes and recurrence risk, openness to clinical trial enrollment, concerns, and information needs. Data were analyzed descriptively; open-ended responses were thematically coded.

Twenty-eight caregivers completed the survey. 86% of children had undergone tumor resection, predominantly for nephroblastoma (85%). Preoperative counseling was considered clear by 79% of caregivers, and perceived support from the medical team was high, with 68% reporting the maximum Likert score (5/5). Prior awareness of FGS was limited (11%); however, after explanation, acceptance was strong. Trust in surgical innovation was high (75% reporting maximum confidence), and 86% believed FGS could improve surgical safety and effectiveness. All respondents reported increased reassurance from the availability of technological support, and 71% perceived a potential reduction in recurrence risk. Emotional responses were predominantly positive, with high levels of confidence, hope, and optimism (75% maximum score), while anxiety, worry, and uncertainty were generally low. Qualitative analysis identified 3 main themes: strong trust and reassurance toward innovation, safety-related concerns focused on toxicity and long-term effects, and a clear need for transparent, detailed risk-benefit information prior to decision-making and potential clinical trial enrollment.

Parents demonstrate high engagement and strong support for FGS, emphasizing the importance of transparent communication, shared decision-making, and active parent-patient involvement to facilitate clinical translation.

The Lynch syndrome INtegrative Epidemiology And GEnetics (LINEAGE) consortium was established to address gaps in understanding genotype-specific cancer risks and risk-modifiers in contemporary North American Lynch syndrome (LS) populations. LINEAGE is a multi-center, longitudinal cohort to systematically collect data on risk factors, adherence to care, quality of surveillance, and patient-, provider-, and system-level factors associated with incident LS-associated cancers.

LINEAGE recruits individuals with confirmed pathogenic or likely pathogenic variants in LS-associated genes from participating institutions. Data includes retrospective and prospective collection, encompassing clinical abstraction (demographics, surgical history, endoscopic data, treatments), patient-reported surveys (behavioral/lifestyle factors, quality of life, procedures), endoscopist-level data, and biosample metadata. A standardized REDCap database, data harmonization protocols, and a virtual biobank support reproducibility and linkage of clinical data and biosamples. Rigorous quality assurance/quality control processes are embedded for data integrity.

Participating centers will contribute data to determine gene-specific risks, and gene-environment interactions for Lynch-associated, and other cancers. We will evaluate associations with exposure to, and quality of cancer risk-reduction care, including endoscopic surveillance, risk-reduction surgery, and chemoprevention. The inclusion of provider-level variables, such as endoscopist training and experience, enables unique research into modifiers of post-endoscopy cancer risk. The linked biosample resources will further facilitate mechanistic studies and biomarker discovery.

LINEAGE provides a robust platform for advancing LS research by integration of clinical, pathological, epidemiological and genetic data across institutions. Its standardized, collaborative framework enhances the validity and generalizability of risk estimates that will guide decision-making and policy for surveillance to ultimately reduce morbidity and mortality for individuals with Lynch syndrome.

Pilonidal sinus disease (PSD) is associated with substantial morbidity because of wound complications and recurrence after surgery. Adjunct laser hair removal (LHR) has been incorporated into postoperative management in some settings, but real-world outcomes in cohorts treated uniformly with LHR remain incompletely described. This study aimed to characterize postoperative outcomes after PSD surgery in a large integrated healthcare system in which adjunctive LHR was standard practice and to compare outcomes by surgical approach. We performed a retrospective descriptive cohort study of patients aged 14-89 years who underwent operative treatment of PSD with adjunctive LHR at Kaiser Permanente Northern California between 2012 and 2024. Outcomes included repeat procedures, 30-day surgical site infection (SSI), and unplanned clinic visits. Outcomes were summarized as proportions overall and by surgical approach. Exploratory bivariable logistic regression examined associations between sex or body mass index (BMI) and outcomes. Multivariable modeling was not performed because of low event counts and sparse covariate distributions, which resulted in unstable models. Among 168 patients, the overall repeat procedure rate was 16.7%, the 30-day SSI rate was 14.4%, and 39.3% had at least one unplanned clinic visit. Patients treated with Bascom flap closure had fewer repeat procedures (10.4% vs. 20.8%) and fewer unplanned visits (33.8% vs. 43.6%) than those undergoing pilocystectomy, with similar SSI rates (14.9% vs. 14.0%). In exploratory analyses, sex and BMI were not significantly associated with outcomes in either surgical group. In this real-world cohort managed uniformly with adjunctive LHR, postoperative outcomes appeared to vary more by surgical approach than by sex or BMI. These findings are descriptive and do not estimate the independent effect of LHR. Controlled comparative studies are needed to determine the contribution of LHR to PSD outcomes.

Multi-omics profiling characterizes cancer biology and supports biomarker discovery for prognosis and therapy selection. Although numerous computational multi-omics biomarker identification methods have been proposed, their ability to identify clinically relevant biomarkers has not been systematically evaluated, leaving it unclear whether the resulting biomarker nominations are reliable for downstream validation. Here, we systematically benchmark 20 representative statistical, machine learning and deep learning methods using curated gold-standard prognostic and therapeutic biomarkers across five real-world datasets. We evaluate performance in terms of both biomarker identification accuracy and stability. Overall, DeePathNet and DeepKEGG achieve the best performance. Across methods, effective biomarker recovery is associated with the integration of biological knowledge, global feature interactions, multivariate feature attribution, and effective regularization. Analysis of omics type contributions reveals method- and modality-specific biases, highlighting the importance of broader omics integration. We further evaluate methods on simulated datasets to probe sensitivity with controlled signal and noise. By aggregating results from top-performing methods, we construct consensus biomarker panels that nominate candidates for potential investigations. Finally, we provide user-friendly interfaces to allow researchers to benchmark new methods against the 20 baselines or apply selected methods for biomarker identification on custom multi-omics datasets. Our benchmark is publicly available at https://github.com/athanzli/CancerMOBI-Bench.

Ovarian cancer represents the primary cause of mortality from gynecological malignancies among women. Treatment strategies for benign versus malignant ovarian tumors differ significantly, making accurate preoperative diagnosis essential for clinical decision-making. Traditional ultrasound diagnosis is highly operator-dependent, introducing subjectivity and variability. To improve diagnostic precision in ovarian tumor classification, we developed a multimodal deep learning system that combines ultrasound images with corresponding clinical text reports.

We retrospectively analyzed 1342 ultrasound images from 1062 patients who received surgical treatment for ovarian tumors at National Taiwan University Hospital from 2011 to 2021. Patients were classified into benign (n = 612) and malignant (including borderline, n = 450) groups based on pathology. A multimodal deep learning architecture was developed, incorporating DenseNet-121 and Swin Transformer for image feature extraction and Bio-Clinical BERT for processing clinical text reports. The dataset was split using subject-level stratification with five-fold cross-validation and a 15% independent test set. Furthermore, an external validation cohort of 268 effective cases from 3 independent medical centers was utilized to evaluate the model's generalizability.

The multimodal model achieved superior performance at the subject level with 81.77% (95% CI: 75.89%, 86.48%) accuracy, 79.59% (95% CI: 70.57%, 86.38%) sensitivity, 83.81% (95% CI: 75.59%, 89.64%) specificity, and an area under the curve (AUC) of 0.88 (95% CI: 0.83, 0.93). In the external validation, the model maintained robust performance with an accuracy of 88.81%, sensitivity of 92.59%, and specificity of 84.96%, outperforming the International Ovarian Tumor Analysis Simple Rules (accuracy 86.4%). Integration of clinical text information significantly improved diagnostic performance compared to image-only models. Backward selection analysis revealed that both uterine findings and ovarian tumor descriptions contributed synergistically to the final diagnosis.

This study successfully developed a multimodal deep learning model with diagnostic performance superior to traditional operator-dependent approaches. The model shows promise as a diagnostic tool for ovarian tumor classification, offering clinicians a way to improve preoperative diagnostic accuracy and enhance patient care quality.

Pelvic radiotherapy (RT) is essential for gynecological cancer; however, it often causes chronic, under-recognized sexual toxicity in survivorship care.

We applied a two-part hurdle model to separately evaluate predictors of sexual activity and function in women receiving RT for gynecological cancers.

We conducted a retrospective cohort study involving 120 women treated with definitive or adjuvant pelvic RT (external beam radiotherapy [EBRT]-inclusive or vaginal brachytherapy [VBT]-only) for gynecological cancer at a single medical center.

The primary outcome was post-treatment sexual function quantified via the 19-item Female Sexual Function Index, while the secondary outcomes included the predictors of sexual activity (binary status defined as any non-zero score on physiological domains) and functional quality (total score) among active women, analyzed using a two-part hurdle model consisting of logistic and beta regressions with a Smithson-Verkuilen transformation.

The cohort exhibited a severe floor effect, with 64.2% (77/120) of patients classified as sexually inactive. In the activity hurdle, lubricant use (OR 12.2; 95% CI: 1.66-88.9; P = .01) and multiparity (OR 12.6; 95% CI, 1.74-91.8; P = .01) were associated with continued sexual engagement, whereas age demonstrated an independent negative association (OR 0.89 per year; 95% CI, 0.81-0.99; P = .04). In the functional hurdle, sexually active patients treated with EBRT-inclusive regimens demonstrated significantly lower functional scores compared to the VBT-only cohort (the exponentiated coefficient of β = 0.17; P = .001). Historical comparisons revealed significant deficits across all domains, especially orgasm (P < .001), within the EBRT-inclusive cohort relative to published healthy controls.

The management of RT-induced sexual dysfunction requires a tiered approach that prioritizes mechanical lubricants to overcome initial activity barriers, while necessitating rehabilitation strategies to mitigate profound functional deficits and to improve the quality of life for patients requiring EBRT.

The main strength is the methodological separation of uncoupling of behavioral engagement hurdles from inherent tissue radiation toxicity; limitations comprise the retrospective design, baseline clinical imbalances between cohorts, and the small number of sexually active patients receiving brachytherapy.

Sexual dysfunction following pelvic RT presents as a complex bifurcated phenomenon, wherein sexual engagement is strongly associated with parity-related anatomical factors and mechanical lubricative support, whereas overall functional quality is constrained by exposure to EBRT.

Colorectal cancer (CRC) remains a leading cause of global cancer-related mortality. Cytidine triphosphate synthase 1 (CTPS1) is an essential enzyme for DNA synthesis and cell cycle progression. While CTPS1 has been implicated in the pathogenesis of various malignancies, its clinical significance in colorectal adenocarcinoma remains poorly defined. This study aimed to investigate the immunohistochemical (IHC) expression of CTPS1 in colorectal adenocarcinoma and evaluate its association with clinicopathological features and survival outcomes. CTPS1 expression was assessed via IHC in 168 colorectal adenocarcinoma specimens and 142 matched adjacent non-neoplastic tissues. Statistical associations with clinicopathological parameters were analyzed using χ2 or Fisher exact tests. Progression-free survival (PFS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and compared via the log-rank test. Multivariate Cox proportional hazards regression was employed to identify independent prognostic factors. CTPS1 expression was significantly upregulated in tumour tissues compared with adjacent normal mucosa (P<0.001). High CTPS1 expression was observed in 55.4% of tumor samples and significantly correlated with advanced T stage, TNM stage, and modified Dukes staging, as well as nodal involvement, distant metastasis, tumor recurrence, and elevated serum CEA levels. Furthermore, elevated CTPS1 was associated with aggressive histologic features, including higher grade, tumor budding, poorly differentiated clusters (PDCs), and tumor deposits. Both PFS and DFS were significantly shorter in patients with high CTPS1 expression (P<0.001). Multivariate analysis confirmed that high CTPS1 expression, along with nodal status and tumor recurrence, was an independent prognostic factor for both PFS and DFS. Therefore, CTPS1 is a robust independent prognostic indicator and a marker of aggressive progression in colorectal adenocarcinoma. These findings suggest that CTPS1 is a promising biomarker for risk stratification and may guide clinical decision-making in the management of CRC.

Immune checkpoint inhibitors can elicit atypical responses such as pseudoprogression (psPD) and mixed responses (MR). We aimed to analyze the occurrence and prognostic impact of atypical responses in metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with ipilimumab/nivolumab.

In this retrospective series of m-ccRCC patients treated with ipilimumab/nivolumab in first-line, we performed radiographic evaluation using Response Evaluation Criteria in Solid Tumors and iRECIST consensus guidelines and compared both methods.

We assessed 258 baseline target lesions in 100 eligible patients. MR occurred in 24% of patients. In 15 patients (62%), the MR evolved to confirmed progressive disease (cPD), while in nine patients (38%), the MR evolved toward a partial response (PR) and was thus a psPD. psPD occurred in 13% of patients: with increase of all lesions in four patients or with MR features in nine patients. psPD patients had the second best time-to-progression (TTP) and cancer-specific survival (CSS), slightly lower compared to TTP and CSS in patients with PR without a phase of psPD and better than TTP and CSS in patients with stable disease as best response. From all patients who presented with PD at first CT evaluation (n = 40), including 17 patients with unconfirmed progressive disease and 23 patients with MR, in 12 (30%) patients this was a psPD and led to a PR.

Atypical responses such as psPD and MR occurred in 13 and 24% of m-ccRCC patients treated with ipilimumab/nivolumab. Patients with psPD had favorable outcomes, while MR in most cases evolved to progression.

IntroductionThis single-center retrospective study aimed to assess the efficacy and safety of first-line rituximab-containing regimens in treatment-naïve patients with mantle cell lymphoma (MCL) in a resource-constrained setting.MethodsWe included 73 patients diagnosed with MCL between May 2019 and June 2024 who received rituximab-based chemotherapy (RB, RBAC, RDHAP, or RCHOP) at the Vietnam National Cancer Hospital. Clinical characteristics, treatment responses, survival outcomes, and prognostic factors were analyzed.ResultsThe median age was 60 years, and the male-to-female ratio was 2.17. Stage IV disease was present in 47.9% of patients and stage III in 38.4%. B symptoms were observed in 27.4%, and Ki-67 >30% in 45.2% of patients. The overall response rate (ORR) was 94.5%, including a complete response rate of 64.4%. The most common grade 3/4 adverse event was neutropenia (17.8%). The 3-year progression-free survival (PFS) and overall survival (OS) rates were 72.6% and 93.2%, respectively. Mantle Cell Lymphoma International Prognostic Index (MIPI) risk classification, treatment response, and extranodal involvement were associated with PFS, whereas OS was primarily influenced by treatment response.ConclusionRituximab-based chemotherapy appears to provide favorable efficacy and manageable toxicity in Vietnamese patients with MCL. These findings suggest that such regimens may remain a feasible first-line option in settings with limited access to novel agents and advanced supportive care.