A self-feedback dual-walker nanosystem for sensitive miRNA detection and intracellular imaging.

Impact of Structured Psychosocial Intervention on Distress in Adolescent and Young Adult Cancer Patients: A Randomized Controlled Trial from India

Colorectal cancer (CRC) patients exhibit distinct gut microbiota disruption, known as dysbiosis, which is believed to play a causative role in CRC. One of the key bacterial species implicated in CRC dysbiosis is Bacteroides fragilis, which presents a paradox as it is also present in most healthy individuals. This discrepancy underscores the need for analysis beyond species-level associations and to investigate intraspecies variation within B. fragilis. From a highly specific collection of B. fragilis isolates from CRC patients and controls, a pangenome-wide association study was conducted, identifying intraspecies genetic variations associated with CRC. The CRC association of these genetic variations were then validated in a metagenome sequencing cohort of faecal samples from 877 individuals, with and without CRC. To test group differences a mixed effects logistic regression with cohort as a random effect was performed for each genetic variation. Here we show that CRC-associated B. fragilis isolates are infected with specific Caudoviricetes prophages, significantly more often than negative controls. The initial discovery was made in our highly specific isolate collection and then validated in an independent metagenome sequencing cohort, finding that CRC patients were twice as likely to have detectable levels of these phages (OR = 2.05, p = 2.522E-7, SE = 0.139). To our knowledge, these findings mark the first link betweenone of the most implicated driver bacteria and phages in CRC and suggest a more complex role of phages in CRC dysbiosis than current models suggest and highlights the potential of phages as CRC biomarkers.

In the last decades, critical advancements in research technology and knowledge on disease mechanisms steered therapeutic approaches for chronic inflammatory diseases towards unprecedented target specificity. For allergic and chronic lung diseases, biologic drugs pioneered this goal, acquiring on the way-through the clinical use of monoclonal antibodies-a deeper understanding of how inflammatory and immune pathways are configured in disease-specific patterns. In this biomarker-driven approach, synthetic small molecule drugs (SMDs) were perceived as lagging behind in innovation for their relative lack of specificity. This was, however, mostly due to a shift in focus towards biologics rather than true obsolescence of SMDs. In the same timeframe, in fact, advances in structural biology and medicinal chemistry, bioinformatics and artificial intelligence held steadily SMDs' innovation and relevance. The use of kinase inhibitors, well established in the treatment of cancer and rheumatological diseases, is now approved for some allergic skin diseases and is approaching asthma and COPD with several clinical trials; moreover, new therapeutics targeting mast cell receptors and molecules involved in innate immunity are entering preclinical and clinical testing. Alongside, the portfolio of biologics is harboring the expansion of RNA therapeutics, which gained global recognition during the COVID-19 pandemic due to RNA vaccines. Different types of RNA therapeutics, including those based on different non-coding RNAs, are advancing to agency approval and market, thanks to improvements in molecule stability and delivery systems. In summary, the evidence presented in this position paper illustrates that precision medicine is becoming a goal shared between synthetic SMDs and biologics, both protein/antibody-based and RNA therapeutics. We review the current state, unmet needs and opportunities within this evolving landscape, highlighting how small molecular species, both synthetic as SMDs and biologic in nature as RNA, can contribute to the precision medicine approach along with protein and antibody-based biologics and cell therapies.

Lived experience and attitudes of esophageal cancer patients toward stenting-based care at Asella referral hospital: a qualitative exploration from a resource-limited setting in South-Eastern Ethiopia.

Breast cancer treatments contribute to bone loss and increase fracture risk, with effects varying by age and menopausal status. Previous studies lacked comparisons with the general population and analyses by treatment and age groups. This study evaluated fracture risk in breast cancer patients compared to a matched control group, considering risk factors, age, and treatments. This retrospective cohort study using the Korean National Health Insurance System database included 104,177 breast cancer patients and 312,531 matched controls. Fracture incidences (any, vertebral, hip, and other) by age and treatment type was assessed using Fine-Gray competing risk models. During the mean follow-up of 7.21years after breast cancer diagnosis, breast cancer patients aged 50years and younger had a higher risk of any fracture (sub-distribution hazard ratio [sHR], 1.33; 95% confidence interval [95% CI], 1.24-1.42) and vertebral fracture (sHR, 1.33; 95% CI, 1.13-1.56) compared to the matched control group. Patients aged 65years and older had a lower risk of any fracture (sHR, 0.91; 95% CI 0.84-0.98) and vertebral fracture (sHR, 0.83; 95% CI, 0.73-0.93). Compared to patients without specified treatments, those who received anthracycline (sHR, 1.21; 95% CI, 1.15-1.28) and aromatase inhibitors (sHR, 1.16; 95% CI, 1.09-1.23) had an increased risk of fracture; and those who were given tamoxifen had a decreased risk (sHR, 0.92; 95% CI, 0.86-0.98). Breast cancer patients had slightly higher fracture risk, primarily in younger patients. Emphasizing osteoporosis prevention and treatment, especially in younger populations or those who have received treatments associated with anincreased risk of fracture, is necessary to reduce fracture risk.

This study aimed to evaluate the risk of doxorubicin-induced cardiotoxicity in newly diagnosed breast cancer patients with type 2 diabetes receiving dapagliflozin in addition to metformin, using echocardiographic methods, and to investigate the potential cardioprotective effects of dapagliflozin. In this prospective observational study, a total of 60 newly diagnosed breast cancer patients with type 2 diabetes were enrolled. Thirty patients who had been treated with metformin and subsequently received dapagliflozin in addition to metformin during doxorubicin therapy constituted the dapagliflozin group. The non-dapagliflozin group consisted of 30 patients who, while continuing metformin, were initiated on another oral antidiabetic agent (excluding dapagliflozin) alongside doxorubicin therapy. N-terminal pro-B type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and left ventricular global longitudinal strain (LVGLS) were measured at baseline and at the 3rd month of treatment. Between-group baseline characteristics were compared using the independent samples t-test for continuous variables. Within-group changes from baseline to 3 months were analyzed with paired t-tests. Between-group comparisons of 3-month outcomes and changes (ΔLVEF, ΔLVGLS, ΔNT-proBNP) were also conducted using independent samples t-tests. To evaluate the independent effect of dapagliflozin on LVGLS, multivariable linear regression analysis was performed. Model fit was reported with adjusted R², F-statistics and 95% confidence intervals. In the non-dapagliflozin group, LVEF and NT-proBNP levels showed no significant differences between baseline and post-treatment; however, LVGLS values significantly deteriorated. In contrast, the dapagliflozin group demonstrated a significant increase in LVEF (- 2.000 [95% CI - 2.392, - 1.608]) and LVGLS (+ 1.367 [95% CI + 1.159, + 1.574]), as well as a marked reduction in NT-proBNP levels (+ 64.933 [95% CI + 57.902, + 71.964]) after 3 months of treatment (p < 0.001). At the third month, the dapagliflozin group exhibited significantly better LVGLS (+ 2.133 [95% CI + 1.346, + 2.921]) and lower NT-proBNP levels (+ 57.000 [95% CI + 28.302, + 85.698]) compared with the non-dapagliflozin group (p < 0.001). Multivariable linear regression analysis confirmed that dapagliflozin use was independently associated with significant improvement in LVGLS at 3 months. In conclusion, dapagliflozin was associated with more favorable short-term surrogate changes in LVGLS and NT-proBNP during doxorubicin therapy. The favorable changes observed in LVEF, LVGLS, and NT-proBNP parameters suggest that dapagliflozin may be considered a potential cardioprotective agent and incorporated into preventive strategies against chemotherapy-related cardiotoxicity in diabetic patients. These hypothesis-generating findings require confirmation in larger randomized trials powered for clinical endpoints with longer follow-up. Not applicable.

Prostate cancer cells of different anatomical locations display remarkable heterogeneity. This poses a challenge to the clinical relevance of pre-clinical models and the efficacy of contemporary therapeutic approaches. Here we develop the snFLARE-seq and mxFRIZNGRND methodologies to directly investigate the transcriptomic and metabolomic landscape of prostate cancer patients utilizing formalin-fixed paraffin-embedded (FFPE) specimens. A retrospective analysis reveals the clinical disparities of prostate cancer from peripheral zone (PZ), transition zone (TZ), and across PZ and TZ. The snFLARE-seq, refined for enhanced single-nucleus sequencing, unveils distinct cell type distributions and signaling pathways between PZ and TZ samples. Hormone therapy substantially affects cancer cells and microenvironment, leading to a polarized feature of epithelial cells and a subverted immune microenvironment. With improvements in metabolite extraction, mxFRIZNGRND reveals unique metabolic features of prostate cancer from different origins. The metabolomic results indicate that PZ cancer cells are in a metabolic-dormant status, which are probably awaken by hormone therapy. Integrative analysis of results from snFLARE-seq, mxFRIZNGRND, and TCGA database uncovers four metabolic pathways and related genes associated with disease aggressiveness. Our work could accelerate investigations on disease heterogeneity and evolution in real-world clinical settings, stimulating patient-specific precision healthcare solutions.

ABSTRACT The technological advancements and climate changes immensely enhanced the exposure of trace/toxic elements to mankind which may be a possible precursor of thyroid diseases including cancer development. However, the data linking them to this malignancy are generally lacking. The current study was designed to explore the role of selected elements that could contribute to the pathogenesis of thyroid diseases. Wet digestion procedure was adopted by using nitric acid perchloric acid mixture and selected elements were measured by flame and hydride generation atomic absorption spectrophotometry. The method was validated by linearity, accuracy, limits of detection and limits of quantification. Average levels (µg/g) of Zn (6.344), Ca (51.61), Cd (0.432), Se (1.995), Cu (1.781), Mg (32.54), Na (491.1), Ni (4.658), Fe (40.99) (p < 0.001) and Hg (0.047) (p < 0.01) were significantly elevated in the thyroid tissues of malignant patients, while mean contents (µg/g) of Mn (0.931), Co (3.078), Li (0.973), As (0.040), Sb (1.759) at p < 0.001, K (286.2) (p < 0.01) and Cr (1.258) (p < 0.05) showed appreciable rise in benign patients. Most of the elements exhibited significant disparities in different types of thyroid cancer patients along with higher accumulation of Cd, Cr and Li were noticed in advanced stages as compared to stage I. Multivariate principal component analysis and hierarchical cluster analysis exhibited diverse apportionment of the elements in both donor groups. The correlation study demonstrated the mutual role of essential and trace/toxic elements in the advancement of thyroid diseases. The comparison among the tissues of malignant and benign patients revealed disproportions in their elemental concentrations. The AAS technique proved to be adequate, as it exhibited good linearity, sensitivity and accuracy for the quantification of elements. Thus statistical mode of elemental analysis may be used as an additional tool for the prediction and progression of the thyroid diseases, including thyroid malignancy.

Primary peritoneal clear cell carcinoma (PPCCC) is an exceptionally rare malignancy that closely resembles gynecologic epithelial cancers clinically and histologically. Its pathogenesis is poorly understood, with possible origins from Müllerian metaplasia or malignant transformation of endometriosis. A 48-year-old woman with no history of endometriosis or hormone therapy presented with acute lower abdominal pain. Imaging revealed a pelvic mass and a lesion in the pancreatic tail. The patient underwent hysterectomy with bilateral salpingo-oophorectomy and distal pancreatectomy with splenectomy. Intraoperatively, the pelvic mass was located in the peritoneum, while the gynecologic organs appeared grossly normal. Histopathologic examination of the pelvic, pancreatic, and splenic lesions revealed identical features of clear cell carcinoma. Immunohistochemistry demonstrated positivity for PAX8, CK7, and HNF1β, with loss of MSH2 and MSH6. Next-generation sequencing revealed ARID1A loss and somatic PIK3CA mutations. No primary ovarian, endometrial, or renal tumor was detected, supporting a diagnosis of primary peritoneal clear cell carcinoma with metastases to the pancreas and spleen. This case highlights the diagnostic challenges of PPCCC and offers valuable insights into the clinical and pathological spectrum of this underrecognized malignancy.

Pneumopericardium is a rare clinical finding in cancer patients and is typically associated with direct tumor invasion or postoperative complications, particularly in intrathoracic malignancies, such as lung or esophageal cancer. Herein, we report the case of a 58-year-old man with advanced gastroesophageal junction adenocarcinoma who developed pneumopericardium and pericarditis in the absence of tumor invasion. The condition was presumed to result from the radial force exerted by a self-expandable metal stent placed for palliation of dysphagia. Computed tomography revealed the presence of air within the pericardial sac and a direct communication with the stent, without radiological evidence of tumor invasion into the pericardium. Given the terminal nature of the disease and lack of response to palliative systemic therapy, the patient was managed conservatively. The patient succumbed to his illness 1.5 months later. To the best of our knowledge, this is the 1st reported case of pneumopericardium induced by the radial force of a self-expandable metal stent in a patient with gastroesophageal junction adenocarcinoma, highlighting the importance of clinical vigilance for pneumopericardium, even in the absence of classic risk factors. Early recognition may guide appropriate management and inform prognostic discussions in patients receiving palliative care.

Objective To evaluate the diagnostic performance and clinical utility of metagenomic next-generation sequencing (mNGS) in distinguishing immune checkpoint inhibitor–related pneumonitis (CIP) from infectious pneumonia in cancer patients undergoing immunotherapy. Methods A retrospective tertiary hospital cohort included 34 cancer patients (Feb 2022–Jan 2024) with prior ICI exposure, new/worsening respiratory symptoms, imaging infiltrates, and both mNGS and conventional microbiological testing (CMT). Final diagnoses were adjudicated by a multidisciplinary panel. We compared pathogen detection rates, sensitivity, specificity, and turnaround times (TAT) between mNGS and CMT. Results In the infectious pneumonia group, mNGS detected pathogens in 17/18 cases (94%), whereas CMT detected only 6/18 (33%). In the CIP group, mNGS was negative in 14/16 cases (88%), compared with 11/16 negatives by CMT (69%). Using the adjudicated diagnosis as the reference, mNGS showed sensitivity 88%, and specificity 94%. In contrast, CMT’s sensitivity was 69%, and specificity 33%. The median TAT for mNGS was 24 hours (IQR 22–31 h), versus 121.5 hours (IQR 80.5–156 h) for CMT (P &amp;lt; 0.001). Conclusion mNGS outperforms CMT in both diagnostic accuracy and timeliness for distinguishing CIP from infectious pneumonia among immunotherapy recipients. Incorporation of mNGS into the diagnostic workflow for suspected CIP may improve etiological discrimination and enable timely, individualized treatment. Further large-scale prospective studies are required to confirm these findings.

Tumor-associated antigen (TAA) vaccines are being explored as a strategy to induce antitumor immune responses. Mammaglobin-A (Mam-A) is a TAA expressed in >50% of breast cancer (BC) patients. Previously, we have shown that Mam-A DNA vaccines induce antitumor immune responses in patients with stable metastatic disease. To further evaluate the potential of the Mam-A vaccine, we initiated a phase-1b clinical trial in estrogen receptor-positive BC patients prior to surgery. Eight patients were assigned to Arm 1 (neoadjuvant endocrine therapy alone) and 17 to Arm 2 (neoadjuvant endocrine therapy plus Mam-A vaccination); the final analysis included 8 patients from Arm 1 and 13 from Arm 2. Ex vivo ELISpot analysis of peripheral blood mononuclear cells demonstrated that Mam-A vaccination induced Mam-A-specific T cells in 8/13 patients. Intracellular cytokine staining, and Mam-A-specific tetramer staining revealed that vaccine-induced Mam-A-specific T cells included both CD4+ and CD8+ polyfunctional T cells. Finally, high-throughput imaging mass cytometry identified 24 cellular meta-clusters with features of tumor, immune, stromal, and endothelial cells and revealed an increased CD8+ T-cell prevalence in the tumor after Mam-A vaccination. In particular, vaccination was associated with the infiltration of PD-1+CD8+ T cells. In addition, post-vaccination tumor samples exhibited close spatial interactions between cytotoxic CD8+ T cells (CTL) and Mam-A+ tumor cells and between CTL and antigen-experienced CD4+ T cells. Together, these results suggest that Mam-A DNA vaccination elicits both systemic and intratumoral antitumor immune responses.

Carotid blowout syndrome is a rare but fatal complication of head and neck cancer. A 62-year-old female patient underwent carotid artery stent implantation for a carotid pseudoaneurysm following multiple surgeries. However, she subsequently presented to the emergency department with bleeding secondary to carotid artery stent extrusion. She underwent emergency surgery, and the carotid artery stent was removed. This case highlights the importance of long-term surveillance of carotid stents in cancer patients who are at risk for tissue necrosis and recurrence.

T cell senescence significantly impairs the efficacy of immune checkpoint blockade (ICB) therapy in cancer. Metabolic reprogramming is a crucial factor in T cell senescence in tumor microenvironment (TME). Ovarian cancer (OvCa) patients derive limited benefit from ICB treatment, probably related to T cell senescence. OvCa cells metastasize to the abdominal cavity rich in omental fat and raise ascites, forming a unique TME, adipocyte-rich TME. In this study, we investigated the effects of adipocyte-rich TME on T cell senescence. Using the single-cell RNA sequencing of OvCa and clinical samples, we found that adipocyte-rich TME is strongly associated with the formation of senescence CD8+T (CD8+Tsen) cells. Mechanistically, adipocyte-derived factors (MATES) and oleic acid (OA)-the predominant fatty acid in OvCa ascites-promoted tumor-induced CD8+Tsen formation by enhancing fatty acid (FA) uptake via FABP4, triggering lipid peroxidation rather than energy production. Inhibition of FABP4 (using the inhibitor BMS309403 or siRNA knockdown) blocked CD8+Tsen cell formation, reduced lipid peroxidation, restored CD8+T cell effector function, and suppressed immunosuppressive cytokines. Moreover, using an OvCa mouse model, we found that in OvCa mice BMS309403 treatment partially diminished CD8+Tsen formation by reducing FA uptake, and improved anti-tumor immunity, and prolonged the survival time of OvCa mice when combined with chemotherapy. Our work suggests FABP4-mediated FA metabolism as a therapeutic target to counteract T cell senescence in adipocyte-rich TME, providing a novel immunotherapeutic strategy for OvCa.

This study details the synthesis, characterization, molecular docking and preliminary biological evaluation of a new heterocyclic compound, 2-((4-morpholino-1,2,5-thiadiazol-3-yl)oxy)benzaldehyde. This molecule was designed using an artificial intelligence (AI)-based molecular generative model. It was synthesized through a nucleophilic substitution between 3-chloro-4-morpholino-1,2,5-thiadiazole and 2-hydroxybenzaldehyde. Structural elucidation was performed using 1H NMR, 13C NMR, Elemental Analysis, and Single Crystal X-ray diffraction. AI-guided in silico predictions suggested promising pharmacophoric features and potential biological activity. Preliminary biological evaluation, primarily through anticancer assays, demonstrated moderate to significant activity, supporting further investigation. The findings therefore suggest that this AI-generated molecule could serve as a lead scaffold for developing drugs targeting cancer and other infectious diseases.

Introduction Internalized stigma adversely impacts childhood cancer survivors, limiting their ability to reintegrate with their communities and maintain social networks. However, the impact of internalized stigma on children undergoing cancer treatment is unknown, and no interventions exist to mitigate it. The Activating Events-Beliefs-Consequences (ABC) model from Cognitive Behavioral Theory (CBT) has been used to analyze internalized stigma and inform interventional work. This study employs the ABC model as a conceptual framework to explore how internalized stigma manifests for children recently diagnosed with osteosarcoma and retinoblastoma in Guatemala, Jordan, and Zimbabwe. Methods We conducted semi-structured interviews with nine adolescent patients (aged 12-18), 28 caregivers, and 19 clinicians at tertiary cancer centers in Guatemala, Jordan, and Zimbabwe. Interviews occurred in Spanish, Arabic, Shona, and English and were transcribed and translated into English for analysis. Two coders independently coded transcripts, resolving disagreements through consensus and third-party adjudication. A framework analysis used the ABC model to understand manifestations of internalized stigma, defined a priori as “a patient’s own adoption of negative societal beliefs or feelings, including changes in self-identification.” Results Patients, caregivers, and clinicians all described internalized stigma in pediatric cancer patients. Cancer-related physical changes and community stigma activated internalized stigma. Patients responded to these events by forming beliefs about their appearance, abilities, normalcy, and future, which shaped their behaviors and emotions. While some patients internalized stigmatizing beliefs about themselves and experienced negative consequences, others maintained resilient self-beliefs that fostered adaptive behaviors and emotions. Knowledge about the disease, supportive interactions with survivors and other patients, and caregiver support promoted stigma resilience. Discussion Our results demonstrate that internalized stigma impacts pediatric cancer patients from the time of diagnosis, highlighting the relevance of the ABC model in understanding this complex phenomenon. Our findings suggest CBT-based interventions that target patient beliefs, address identified activating events, and enhance multilevel support could help mitigate internalized stigma in pediatric cancer patients. Additional research should explore the efficacy of such interventions, the transferability of our findings to children with other cancer diagnoses and to various geographies, as well as how internalized stigma evolves across the cancer continuum.

DNA methylation analysis of self-collected samples has shown potential for primary endometrial cancer detection. Here, we aimed to explore DNA methylation testing as a non-invasive alternative for post-treatment surveillance. Endometrial cancer patients (n = 43) without recurrence collected pre- and post-treatment cervicovaginal self-samples and urine at home. Additionally, 17 patients with recurrence provided these samples at the time of recurrence. Healthy controls were used as reference. In total, 207 cervicovaginal self-samples and 203 urine samples were tested for nine markers (ADCYAP1, BHLHE22, CDH13, CDO1, GALR1, GHSR, HAND2, SST and ZIC1) using quantitative methylation-specific PCR. Diagnostic performance was assessed using previously established logistic regression models. In patients without recurrence, most marker levels decreased post-treatment compared to pre-treatment, in both sample types. DNA methylation positivity in cervicovaginal self-samples reduced from 90.7% pre-treatment to 19.5% post-treatment (p < .0001). In urine, a decrease from 80.5% to 20.9% was observed (p < .0001). In patients with recurrence, DNA methylation levels of CDH13, CDO1, GALR1, GHSR and HAND2 in cervicovaginal self-samples, and CDO1, GHSR and HAND2 in urine, were higher than in patients without recurrence. DNA methylation positivity was 62.5% in cervicovaginal self-samples and 58.8% in urine among patients with any recurrence, and 100% in cervicovaginal self-samples and 90.0% in urine of patients with a local recurrence specifically. These findings support methylation-based testing as a promising post-treatment surveillance method for endometrial cancer patients. This non-invasive approach could reduce the follow-up burden on patients and healthcare, alleviating challenges related to resource constraints while improving patient comfort.

Paclitaxel being an effective treatment for ovarian cancer, presents one of the most critical toxicities; peripheral neuropathy (PN), a debilitating side effect that might limit continuation of chemotherapy. Vitamin B was found to significantly improve PN and Gabapentin is debatably used in chemotherapy induced peripheral neuropathy (CIPN). The aim of this study was to assess the efficacy of vitamin B prophylaxis in reducing the severity of CIPN, particularly in diabetic patients with the need for Gabapentin as additional therapy and the potential impact on disease response. A clinical trial of 146 adult ovarian cancer patients received Paclitaxel for 18 weeks; randomly allocated into two arms: One arm received vitamin B prophylaxis before starting Paclitaxel and other received upon CIPN. Gabapentin was given upon aggravation of CIPN. This study showed a significant reduction in CIPN grade over time, with fewer patients progressed to higher grades in prophylactic versus non-prophylactic group, extended to significant improvement in CIPN in prophylactic versus non-prophylactic diabetic patients. Gabapentin was more significantly required in non-prophylactic versus prophylactic group. A significant correlation was found between dose modification due to CIPN and CA125 status. Finally, a significant difference in PFS between prophylactic and non-prophylactic group was found at the end of the study. These results reinforce the potential role of vitamin B prophylaxis in improving patient outcomes through significantly reducing CIPN severity and minimizing the risk of dose reductions, thereby contributing to better disease response. Trial registration number: NCT07191587, date of registration: 09/24/2025, retrospectively registered.

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