Non-invasive vagus nerve stimulation in anti-inflammatory therapy: mechanistic insights and future perspectives.

Non-invasive vagus nerve stimulation (VNS) represents a transformative approach for managing a broad spectrum of inflammatory and autoimmune conditions, including rheumatoid arthritis and inflammatory bowel disease. This comprehensive review delineates the mechanisms underlying VNS, emphasizing the cholinergic anti-inflammatory pathway, and explores interactions within the neuro-immune and vagus-gut axes based on both clinical outcomes and pre-clinical models. Clinical applications have confirmed the efficacy of VNS in managing specific autoimmune diseases, such as rheumatoid arthritis, and chronic inflammatory conditions like inflammatory bowel disease, showcasing the variability in stimulation parameters and patient responses.

Assessing the impact of deep-learning assistance on the histopathological diagnosis of serous tubal intraepithelial carcinoma (STIC) in fallopian tubes.

In recent years, it has become clear that artificial intelligence (AI) models can achieve high accuracy in specific pathology-related tasks. An example is our deep-learning model, designed to automatically detect serous tubal intraepithelial carcinoma (STIC), the precursor lesion to high-grade serous ovarian carcinoma, found in the fallopian tube. However, the standalone performance of a model is insufficient to determine its value in the diagnostic setting.

Myasthenia gravis and covid-19 in pregnancy: a review of the literature and case series report.

Objectives: The aim of our study was to investigate the interrelations of symptoms, clinical outcomes and treatment regimens in pregnant women, diagnosed with myasthenia gravis and superimposed COVID-19 infection.

Methods: We conducted an observational retrospective study between August, 2020 and July, 2021. Five patients with preexisting MG and superimposed COVID- infection were included in our study.

Phase III randomized, double-blind study of paclitaxel with and without everolimus in patients with advanced gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen (RADPAC).

The RADPAC trial evaluated paclitaxel with everolimus in patients with advanced gastroesophageal cancer (GEC) who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen. Patients were randomly assigned to receive paclitaxel (80 mg/m ) on day 1, 8 and 15 plus everolimus (10 mg daily, arm B) d1-d28 or placebo (arm A), repeated every 28 days. Primary end point was overall survival (OS).

Randomised phase II trial of trofosfamide vs. doxorubicin in elderly patients with untreated metastatic soft-tissue sarcoma.

Doxorubicin represents the standard first-line treatment for metastatic soft-tissue sarcoma. We assessed the efficacy and safety of trofosfamide in elderly patients. In this controlled phase II trial, we randomly (1:2) assigned 120 previously untreated patients with soft-tissue sarcoma, older than 60 years, with an Eastern Cooperative Oncology Group score of 0-2, to receive either doxorubicin for 6 cycles (arm A) or oral trofosfamide (arm B).

Exacerbation of hepatitis E virus infection during anti-TNFα treatment.

Chronic hepatitis E virus (HEV) infection may occur in immunocompromised patients. Previous studies report that different immunosuppressive agents interfere with viral replication. However, the role of TNFα in HEV infection is currently unknown.

Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).

Background: Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure.

Patients And Methods: Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B).

The use of collagen-based matrices in the treatment of full-thickness wounds.

Chronic and complex full-thickness wounds have become increasingly prevalent. Besides autologous skin transplantation, innovative wound dressing products have gained interest, as the functional and esthetic outcome is still limited. In this respect, the effect of a novel modifiable collagen-gelatin fleece on the healing of deep dermal wounds was examined and compared with untreated controls and Matriderm(®).

The regulatory interaction of EVI1 with the TCL1A oncogene impacts cell survival and clinical outcome in CLL.

Dysregulated T-cell leukemia/lymphoma-1A (TCL1A), a modulator in B-cell receptor (BCR) signaling, is causally implicated in chronic lymphocytic leukemia (CLL). However, the mechanisms of the perturbed TCL1A regulation are largely unknown. To characterize TCL1A-upstream networks, we functionally screened for TCL1A-repressive micro-RNAs (miRs) and their transcriptional regulators.

Paraneoplastic granulocyte colony-stimulating factor secretion in soft tissue sarcoma mimicking myeloproliferative neoplasia: a case report.

Background: While paraneoplastic leukocytosis is a common phenomenon in solid tumors, extreme elevations of white blood counts (WBC) in the range of more than 100,000/μl are uncommon in patients with non-hematologic malignancies. Leukocytosis with mature neutrophils due to a granulocyte colony-stimulating factor (G-CSF) producing tumor is only seen on rare occasions.

Case Presentation: Massive neutrophil leukocytosis of approximately 100,000/μl was diagnosed in a 57-year-old Caucasian woman with metastatic undifferentiated endometrial sarcoma.

Expression and role of the embryonic protein SOX2 in head and neck squamous cell carcinoma.

Recently, SOX2 has been identified as a potential lineage-specific oncogene in lung squamous cell carcinomas. Since head and neck squamous cell carcinomas (HNSCC) are morphologically and clinically highly related to lung squamous cell carcinomas, we hypothesized that SOX2 also plays an oncogenic role in this tumor entity. We assembled a cohort of 496 patients with HNSCC, including 253 metastases and 135 recurrences.

Steady-state neutrophil homeostasis is dependent on TLR4/TRIF signaling.

Unlabelled: Polymorphonuclear neutrophil granulocytes (neutrophils) are tightly controlled by an incompletely understood homeostatic feedback loop adjusting the marrow's supply to peripheral needs. Although it has long been known that marrow cellularity is inversely correlated with G-CSF levels, the mechanism linking peripheral clearance to production remains unknown. Herein, the feedback response to antibody induced neutropenia is characterized to consist of G-CSF–dependent shifts of marrow hematopoietic progenitor populations including expansion of the lin-/Sca-1/c-kit (LSK) and granulocyte macrophage progenitor (GMP) compartments at the expense of thrombopoietic and red cell precursors.

Zebrafish xenografts as a tool for in vivo studies on human cancer.

The zebrafish has become a powerful vertebrate model for genetic studies of embryonic development and organogenesis and increasingly for studies in cancer biology. Zebrafish facilitate the performance of reverse and forward genetic approaches, including mutagenesis and small molecule screens. Moreover, several studies report the feasibility of xenotransplanting human cells into zebrafish embryos and adult fish.

EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute lymphoblastic leukemia.

The transcriptional regulator ecotropic viral integration site-1 (EVI-1) has mainly been studied for its role in myeloid malignancies, in which high EVI-1 levels are associated with particularly aggressive disease. The role of EVI-1 in lymphoid cells, however, is largely unknown. Here we show that EVI-1 is indeed expressed in lymphoid malignancies such as acute lymphoblastic leukemia (ALL) and a subset of chronic lymphocytic leukemia.

EGFR-TKI resistant non-small cell lung cancer (NSCLC): new developments and implications for future treatment.

Treatment with receptor-tyrosine kinase inhibitors (TKIs) has improved progression-free and overall survival in patients with advanced non-small cell lung cancer (NSCLC). One major target for treatment with TKI is the epidermal growth factor receptor (EGFR), particularly in patients harboring activating mutations. However, despite initial responses and long lasting remissions, the development of secondary resistance inevitably leads to treatment failure.

Interactions between Cdx genes and retinoic acid modulate early cardiogenesis.

Cdx transcription factors regulate embryonic positional identities and have crucial roles in anteroposterior patterning (AP) processes of all three germ layers. Previously we have shown that the zebrafish homologues cdx1a and cdx4 redundantly regulate posterior mesodermal derivatives inducing embryonic blood cell fate specification and patterning of the embryonic kidney. Here we hypothesize that cdx factors restrict formation of anterior mesodermal derivatives such as cardiac cells by imposing posterior identity to developing mesodermal cells.

Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma.

Background: The SRY-related HMG-box family of transcription factors member SOX2 has been mainly studied in embryonic stem cells as well as early foregut and neural development. More recently, SOX2 was shown to participate in reprogramming of adult somatic cells to a pluripotent stem cell state and implicated in tumorigenesis in various organs. In breast cancer, SOX2 expression was reported as a feature of basal-like tumors.

Autologous blood cell therapies from pluripotent stem cells.

The discovery of human embryonic stem cells (hESCs) raised promises for a universal resource for cell based therapies in regenerative medicine. Recently, fast-paced progress has been made towards the generation of pluripotent stem cells (PSCs) amenable for clinical applications, culminating in reprogramming of adult somatic cells to autologous PSCs that can be indefinitely expanded in vitro. However, besides the efficient generation of bona fide, clinically safe PSCs (e.

Hematopoietic development from human induced pluripotent stem cells.

A decade of research on human embryonic stem cells (ESC) has paved the way for the discovery of alternative approaches to generating pluripotent stem cells. Combinatorial overexpression of a limited number of proteins linked to pluripotency in ESC was recently found to reprogram differentiated somatic cells back to a pluripotent state, enabling the derivation of isogenic (patient-specific) pluripotent stem cell lines. Current research is focusing on improving reprogramming protocols (e.

Disease models from pluripotent stem cells.

Murine models of congenital and acquired diseases are invaluable yet often do not faithfully mirror human pathophysiology. Embryonic stem (ES) cells differentiated in vitro recapitulate aspects of early embryogenesis and differentiate into multiple somatic tissues, thereby serving as a powerful platform for developmental studies in the human. Analysis of genetically modified ES cells (by lentiviral gene transduction or derivation from embryos carrying genetic diseases, for example) offers the unprecedented opportunity to study in detail disease initiation and progression during embryonic development.

Patient-specific pluripotent stem cells: promises and challenges.

Tissue transplantation is a well-established tool for the treatment of degenerative and malignant disorders, yet its use in clinical practice is hampered by the need for human-leukocyte-antigen-compatible donors and a shortage of suitable graft tissue. The discovery of human embryonic stem cells a decade ago raised hopes that a universal resource for the cell-based treatment of various conditions would soon become available. Embryonic stem cells derived by somatic-cell nuclear transfer or parthenogenesis can provide human-leukocyte-antigen-matched cells, which may be transplanted without the need for immunosuppressive treatment.

Aberrant expression of the homeobox gene CDX2 in pediatric acute lymphoblastic leukemia.

Members of the caudal (cdx) family of homeobox proteins are essential regulators of embryonic blood development in zebrafish. Previously, we reported that the murine homologues (Cdx1, Cdx2, and Cdx4) affect formation and differentiation of embryonic stem cell (ESC)-derived hematopoietic progenitor cells. Consistent with the notion that embryonic pathways can reactivate during adult oncogenesis, recent studies suggest involvement of CDX2 in human acute myeloid leukemia (AML).

Contamination of autologous peripheral blood progenitor cell grafts predicts overall survival after high-dose chemotherapy in multiple myeloma.

Background: Despite of the introduction of novel treatment modalities for multiple myeloma, high-dose chemotherapy with hematopoietic stem-cell rescue is still considered the standard of care for eligible patients <65 years of age. As we have previously reported, stem-cell grafts regularly contain quantities of plasma cells measurable by flow cytometry. However, the pathogenetic significance of this finding remains unknown.