Vvax001, a Therapeutic Vaccine for Patients with HPV16-positive High-grade Cervical Intraepithelial Neoplasia: a Phase II Trial.

Purpose: Human papillomavirus (HPV) infection is the major cause of (pre)malignant cervical lesions. We previously demonstrated that Vvax001, a replication-incompetent Semliki Forest virus (SFV) vaccine encoding HPV type 16 (HPV16) E6 and E7, induced potent anti-E6 and -E7 cytotoxic T-cell responses. Here, we investigated the clinical efficacy of Vvax001 in patients with HPV16-positive cervical intraepithelial neoplasia grade 3 (CIN3).

Crafting Hollow Spheres via Bulk Ice Melting with ppb-Level Gas Sensing Performance.

Ice melting, a common yet complex phenomenon, remains incompletely understood. While theoretical studies suggest that preexisting defects in ice generate "off-lattice" water molecules, triggering bulk ice melting, direct experimental evidence of their form has been lacking as the transparent and transient nature of ice poses significant challenges for observation with current techniques. Here, we introduce an ice-melting-induced lyophilization (IMIL) technique that employs graphene-based nanoprobes to replicate and track liquid evolution within melting bulk ice.

Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study.

Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response.

B cells critical for outcome in high grade serous ovarian carcinoma.

Recent work has shown evidence for the prognostic significance of tumor infiltrating B cells (B-TIL) in high grade serous ovarian carcinoma (HGSOC), the predominant histological subtype of ovarian cancer. However, it remains unknown how the favorable prognosis associated with B-TIL relates to the current standard treatments of primary debulking surgery (PDS) followed by chemotherapy or (neo-)adjuvant chemotherapy (NACT) combined with interval debulking surgery. To address this, we analyzed the prognostic impact of B-TIL in relationship to primary treatment and tumor infiltrating T cell status in a highly homogenous cohort of HGSOC patients.

Large-Area and Visible-Light-Driven Heterojunctions of InO/Graphene Built for ppb-Level Formaldehyde Detection at Room Temperature.

Achieving convenient and accurate detection of indoor ppb-level formaldehyde is an urgent requirement to ensure a healthy working and living environment for people. Herein, ultrasmall InO nanorods and supramolecularly functionalized reduced graphene oxide are selected as hybrid components of visible-light-driven (VLD) heterojunctions to fabricate ppb-level formaldehyde (HCHO) gas sensors (named InAG sensors). Under 405 nm visible light illumination, the sensor exhibits an outstanding response toward ppb-level HCHO at room temperature, including the ultralow practical limit of detection (pLOD) of 5 ppb, high response (/ = 2.

Assembly of Core/Shell Nanospheres of Amorphous Hemin/Acetone-Derived Carbonized Polymer with Graphene Nanosheets for Room-Temperature NO Sensing.

Implementing parts per billion-level nitric oxide (NO) sensing at room temperature (RT) is still in extreme demand for monitoring inflammatory respiratory diseases. Herein, we have prepared a kind of core-shell structural Hemin-based nanospheres (Abbr.: Hemin-nanospheres, defined as HNSs) with the core of amorphous Hemin and the shell of acetone-derived carbonized polymer, whose core-shell structure was verified by XPS with argon-ion etching.

A rare case of epithelial-myoepithelial carcinoma arising ex pleomorphic adenoma of the lacrimal gland: case report and review of the literature.

A 92-year-old man presented with progressively worsening eye pain, diplopia on lateral gaze and blurred vision for the past 12 months. Radiological imaging confirmed a large left lacrimal gland lesion. The patient subsequently underwent a superio-lateral orbitotomy with left dacryoadenectomy and tumor removal, histopathology subsequently confirmed an epithelial-myoepithelial carcinoma arising ex pleomorphic adenoma of the lacrimal gland.

Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial Cancer.

Identification of human cancer-reactive CD8+ T cells is crucial for the stratification of patients for immunotherapy and determination of immune-therapeutic effects. To date, these T cells have been identified mainly based on cell surface expression of programmed cell death protein 1 (PD-1) or co-expression of CD103 and CD39. A small subset of CD103- CD39+ CD8+ T cells is also present in tumors, but little is known about these T cells.

CarbonIron Electron Transport Channels in Porphyrin-Graphene Complex for ppb-Level Room Temperature NO Gas Sensing.

It is a great challenge to develop efficient room-temperature sensing materials and sensors for nitric oxide (NO) gas, which is a biomarker molecule used in the monitoring of inflammatory respiratory diseases. Herein, Hemin (Fe (III)-protoporphyrin IX) is introduced into the nitrogen-doped reduced graphene oxide (N-rGO) to obtain a novel sensing material HNG-ethanol. Detailed XPS spectra and DFT calculations confirm the formation of carbon-iron bonds in HNG-ethanol during synthesis process, which act as electron transport channels from graphene to Hemin.

Assembling Hollow Cactus-Like ZnO Nanorods with Dipole-Modified Graphene Nanosheets for Practical Room-Temperature Formaldehyde Sensing.

Formaldehyde (HCHO) sensing plays a critical role for indoor environment monitoring in smart home systems. Inspired by the unique hierarchical structure of cactus, we have prepared a ZnO/ANS-rGO composite for room-temperature (RT) HCHO sensing, through assembling hollow cactus-like ZnO nanorods with 5-aminonaphthalene-1-sulfonic acid (ANS)-modified graphene nanosheets in a facile and template-free manner. Interestingly, it was found that the ZnO morphology could be simply tuned from flower clusters to hollow cactus-like nanostructures, along with the increase of the reaction time during the assembly process.

Rapid and efficient generation of antigen-specific isogenic T cells from cryopreserved blood samples.

Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated gene editing has been leveraged for the modification of human and mouse T cells. However, limited experience is available on the application of CRISPR/Cas9 electroporation in cryopreserved T cells collected during clinical trials. To address this, we aimed to optimize a CRISPR/Cas9-mediated gene editing protocol compatible with peripheral blood mononuclear cells (PBMCs) samples routinely produced during clinical trials.

Charge transfer driven by redox dye molecules on graphene nanosheets for room-temperature gas sensing.

Special functional groups to modify the surface of graphene have received much attention since they enable the charge transfer enhancement, thus realizing gas-sensing at room temperature. In this work, three typical redox dye molecules, methylene blue (MB), indigo carmine (IC) and anthraquinone-2-sulfonate (AQS), were selected to be supramolecularly assembled with reduced graphene oxide (rGO), respectively. Remarkably, three graphene-based materials AQS-rGO (response = 3.

CD20 positive CD8 T cells are a unique and transcriptionally-distinct subset of T cells with distinct transmigration properties.

The presence of T cells that are dimly positive for the B cell marker CD20 is well-established in autoimmunity and correlates with disease severity in various diseases. Further, we previously identified that the level of CD20-positive T cells was three-fourfold elevated in ascites fluid of ovarian carcinoma patients, together suggesting a role in both autoimmunity and cancer. In this respect, treatment of autoimmune patients with the CD20-targeting antibody Rituximab has also been shown to target and deplete CD20-positive T cells, previously identified as IFN-gamma producing, low proliferative, CD8 cytotoxic T cells with an effector memory (EM) differentiation state.

[How "elderly-proof" are the current medical specialist guidelines in the Netherlands?].

The prevalence of multimorbidity increases with age, with over 70% of people aged 75 years and over having three or more chronic conditions, often combined with frailty. In current medical practice, evidence-based medicine with evidence-based guidelines forms the basis for treatment. The aim of this study is to determine the practical applicability of the current medical specialist guidelines for the treatment of the heterogeneous group of older patients.

A Photovoltaic Self-Powered Gas Sensor Based on All-Dry Transferred MoS /GaSe Heterojunction for ppb-Level NO Sensing at Room Temperature.

Traditional gas sensors are facing the challenge of low power consumption for future application in smart phones and wireless sensor platforms. To solve this problem, self-powered gas sensors are rapidly developed in recent years. However, all reported self-powered gas sensors are suffering from high limit of detection (LOD) toward NO gas.

Association of homozygous variants of STING1 with outcome in human cervical cancer.

DNA-sensing receptor Cyclic GMP-AMP Synthase (cGAS) and its downstream signaling effector STimulator of INterferon Genes (STING) have gained significant interest in the field of tumor immunology, as a dysfunctional cGAS-STING pathway is associated with poor prognosis and worse response to immunotherapy. However, studies so far have not taken into account the polymorphic nature of the STING-encoding STING1 gene. We hypothesized that the presence of allelic variance in STING1 would cause variation between individuals as to their susceptibility to cancer development, cancer progression, and potential response to (immuno)therapy.

All-Dry Transferred ReS Nanosheets for Ultrasensitive Room-Temperature NO Sensing under Visible Light Illumination.

For gas sensing applications, most of the reported two-dimensional (2D) materials are suffering from relatively low sensitivity and high limit of detection (LOD) at room temperature. In this work, we selected rhenium disulfide (ReS) nanosheets to fabricate ReS transistor-based gas sensors (RTGSs) with ultrahigh sensitivity and low LOD toward nitrogen dioxide (NO). The ReS nanosheets with different thicknesses were prepared mechanical exfoliation and all-dry transfer method.

Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up.

Unlabelled: Treatment of metastatic melanoma with autologous tumor infiltrating lymphocytes (TILs) is currently applied in several centers. Robust and remarkably consistent overall response rates, of around 50% of treated patients, have been observed across hospitals, including a substantial fraction of durable, complete responses.

Purpose: Execute a phase I/II feasibility study with TIL therapy in metastatic melanoma at the Netherlands Cancer Institute, with the goal to assess feasibility and potential value of a randomized phase III trial.

Cluster of pregnancy-associated melanoma: A case report and brief update.

Melanoma incidence is increasing globally with Australia having the highest incidence in the world. Pregnancy-associated melanoma is recognized in the published work; however, significant knowledge deficiencies exist. We present the case of a 34-year-old woman with dysplastic nevus syndrome who over a 15-year period developed a total of nine melanomas, with eight clustered around an 18-month peri- to post-partum period.

Transcriptional Activity and Stability of CD39+CD103+CD8+ T Cells in Human High-Grade Endometrial Cancer.

Tumor-infiltrating CD8+ T cells (TIL) are of the utmost importance in anti-tumor immunity. CD103 defines tumor-resident memory T cells (T cells) associated with improved survival and response to immune checkpoint blockade (ICB) across human tumors. Co-expression of CD39 and CD103 marks tumor-specific T with enhanced cytolytic potential, suggesting that CD39+CD103+ T could be a suitable biomarker for immunotherapy.

Synergy of CO-response and aggregation induced emission in a small molecule: renewable liquid and solid CO chemosensors with high sensitivity and visibility.

A tetraphenylethylene (TPE) derivative (N,N-dimethyl-N'-(4-(1,2,2-triphenylvinyl)phenyl)acetimidamide, TPE-amidine) was designed and synthesized, and used to prepare visible CO chemosensors, TPE-amidine-L (liquid) and TPE-amidine-S (solid). The hydrophilicity of TPE-amidine thoroughly changed because of the unique reversible reaction between the amidine group and CO, which controlled the molecular aggregation extent in water by CO. Combining with the well-known aggregate-induced emission effect, the highly selective CO chemosensor TPE-amidine-L was developed, which has the lowest CO detection limit of 24.