Iron transfer across a functional syncytialized trophoblast monolayer.

Studying iron transfer across trophoblast monolayers is crucial given the significance of iron in maintaining a healthy pregnancy and supporting fetal growth and development. To get insights into the complex mechanism of transplacental iron transfer, we developed a standardized Transwell®-based monolayer model using BeWo (clone b30) cells. Our proposed method is divided into two parts: 1.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

"Pyogenic spondylodiscitis from oral odontogenic origins: a frequently overlooked entity".

Background Context: Primary spondylodiscitis occurs through the hematogenous spread of a pathogen entering the body via a point of entry. The infection's origin often remains unclear. During dental procedures or through minor traumas, oral bacteria can enter the bloodstream and disseminate throughout the body.

Endovascular therapy for cerebral vasospasm after aneurysmal subarachnoid hemorrhage: Single-center experience in a high-volume neurovascular unit.

Introduction: Despite targeted standard therapy, aneurysmal subarachnoid hemorrhage (aSAH) frequently leads to cerebral vasospasms (CVS) of large cerebral arteries, reduced oxygen supply of brain tissue, known as delayed cerebral ischemia (DCI), subsequent development of manifest cerebral infarction and poor neurological outcome.

Research Question: The primary aim was to evaluate the efficacy of endovascular spasmolysis (eSL) as a rescue therapy for delayed ischemic neurological deficits (DIND) occurring despite maximum conservative treatment, with the potential benefit of preventing permanent ischemic deficits, and thus, improving overall neurological outcomes.

Material And Methods: In our retrospective, monocentric study, we included 310 patients developing CVS during hospitalization and evaluated their clinical and radiographic outcomes.

Environmental DNA barcoding reveals general biodiversity patterns in the large tropical rift Lake Albert.

Lake Albert, Africa's seventh-largest lake and a biodiversity hotspot, faces significant environmental challenges, including unregulated anthropogenic pressure and a lack of comprehensive biological studies. To address the scarcity of biodiversity data, we utilized environmental DNA (eDNA) metabarcoding to assess the lake's eukaryotic and metazoan communities. Surface water samples were collected at three distinct locations: close to the southern inflow of the Semliki River, the central part of the lake, and close to the northern inflow of the Victoria Nile and outflow of the Albert Nile.

Modelling the maternal-fetal interface: An in vitro approach to investigate nutrient and drug transport across the human placenta.

The placenta plays a critical role in maternal-fetal nutrient transport and fetal protection against drugs. Creating physiological in vitro models to study these processes is crucial, but technically challenging. This study introduces an efficient cell model that mimics the human placental barrier using co-cultures of primary trophoblasts and primary human umbilical vein endothelial cells (HUVEC) on a Transwell-based system.

The risk of second malignancies following prostate cancer radiotherapy in the era of conformal radiotherapy: a statement of the Prostate Cancer Working Group of the German Society of Radiation Oncology (DEGRO).

A significant number of prostate cancer patients are long-term survivors after primary definitive therapy, and the occurrence of late side effects, such as second primary cancers, has gained interest. The aim of this editorial is to discuss the most current evidence on second primary cancers based on six retrospective studies published in 2021-2024 using large data repositories not accounting for all possible confounding factors, such as smoking or pre-existing comorbidities. Overall, prostate cancer patients treated with curative radiotherapy have an increased risk (0.

Two-photon excitation two-dimensional fluorescence spectroscopy (2PE-2DFS) of the fluorescent nucleobase 6-MI.

Base stacking is fundamentally important to the stability of double-stranded DNA. However, few experiments can directly probe the local conformations and conformational fluctuations of the DNA bases. Here we report a new spectroscopic approach to study the local conformations of DNA bases using the UV-absorbing fluorescent guanine analogue, 6-methyl isoxanthopterin (6-MI), which can be used as a site-specific probe to label DNA.

Co-targeting SOS1 enhances the antitumor effects of KRAS inhibitors by addressing intrinsic and acquired resistance.

Combination approaches are needed to strengthen and extend the clinical response to KRAS inhibitors (KRASi). Here, we assessed the antitumor responses of KRAS mutant lung and colorectal cancer models to combination treatment with a SOS1 inhibitor (SOS1i), BI-3406, plus the KRAS inhibitor, adagrasib. We found that responses to BI-3406 plus adagrasib were stronger than to adagrasib alone, comparable to adagrasib with SHP2 (SHP2i) or EGFR inhibitors and correlated with stronger suppression of RAS-MAPK signaling.

Control of schistosomiasis by the selective competitive and predatory intervention of intermediate hosts: A mathematical modeling approach.

Schistosomiasis, a freshwater-borne neglected tropical disease, disproportionately affects impoverished communities mainly in the tropical regions. Transmission involves humans and intermediate host (IH) snails. This manuscript introduces a mathematical model to probe schistosomiasis dynamics and the role of non-host snail competitors and predators as biological control agents for IH snails.

Amplicon-Based Bisulfite Conversion-NGS DNA Methylation Analysis Protocol.

DNA methylation is an important epigenetic modification that regulates chromatin structure and the cell-type-specific expression of genes. The association of aberrant DNA methylation with many diseases, as well as the increasing interest in modifying the methylation mark in a directed manner at genomic sites using epigenome editing for research and therapeutic purposes, increases the need for easy and efficient DNA methylation analysis methods. The standard approach to analyze DNA methylation with a single-cytosine resolution is bisulfite conversion of DNA followed by next-generation sequencing (NGS).

Alterations of Placental Sodium in Preeclampsia: Trophoblast Responses.

Background: Evidence suggests that increasing salt intake in pregnancy lowers blood pressure, protecting against preeclampsia. We hypothesized that sodium (Na) evokes beneficial placental signals that are disrupted in preeclampsia.

Methods: Blood and urine were collected from nonpregnant women of reproductive age (n=26) and pregnant women with (n=50) and without (n=55) preeclampsia, along with placental biopsies.

Prediction of tumor-specific splicing from somatic mutations as a source of neoantigen candidates.

Motivation: Neoantigens are promising targets for cancer immunotherapies and might arise from alternative splicing. However, detecting tumor-specific splicing is challenging because many non-canonical splice junctions identified in tumors also appear in healthy tissues. To increase tumor-specificity, we focused on splicing caused by somatic mutations as a source for neoantigen candidates in individual patients.

Donor regulatory T cells rapidly adapt to recipient tissues to control murine acute graft-versus-host disease.

The adoptive transfer of regulatory T cells is a promising strategy to prevent graft-versus-host disease after allogeneic bone marrow transplantation. Here, we use a major histocompatibility complex-mismatched mouse model to follow the fate of in vitro expanded donor regulatory T cells upon migration to target organs. Employing comprehensive gene expression and repertoire profiling, we show that they retain their suppressive function and plasticity after transfer.

Spectroscopic approaches for studies of site-specific DNA base and backbone 'breathing' using exciton-coupled dimer-labeled DNA.

DNA regulation and repair processes require direct interactions between proteins and DNA at specific sites. Local fluctuations of the sugar-phosphate backbones and bases of DNA (a form of DNA 'breathing') play a central role in such processes. Here we review the development and application of novel spectroscopic methods and analyses - both at the ensemble and single-molecule levels - to study structural and dynamic properties of exciton-coupled cyanine and fluorescent nucleobase analogue dimer-labeled DNA constructs at key positions involved in protein-DNA complex assembly and function.

Citizens can help to map putative transmission sites for snail-borne diseases.

Introduction: Schistosomiasis and fasciolosis are snail-borne diseases of great medical and veterinary health importance. The World Health Organization recommends complementing drug treatment with snail control and community involvement for disease elimination, but there is a general lack of snail experts and hence snail distribution data. Therefore, we adopted a citizen science approach and involved citizens in the monitoring of medically and veterinary important snail taxa.

Obesogenic diet in pregnancy disrupts placental iron handling and ferroptosis and stress signalling in association with fetal growth alterations.

Obesity and gestational diabetes (GDM) impact fetal growth during pregnancy. Iron is an essential micronutrient needed for energy-intense feto-placental development, but if mis-handled can lead to oxidative stress and ferroptosis (iron-dependent cell death). In a mouse model showing maternal obesity and glucose intolerance, we investigated the association of materno-fetal iron handling and placental ferroptosis, oxidative damage and stress signalling activation with fetal growth.

Impact of function-guided glioma treatment on oncological outcome in the elderly.

Introduction: Many patients with high-grade gliomas (HGG) are of older age.

Research Question: We hypothesize that pre- and intraoperative mapping and monitoring preserve functional status in elderly patients while gross total resection (GTR) is the aim, resulting in overall survival (OS) rates comparable to the general population with HGG.

Material And Methods: We subdivided a prospective cohort of 168 patients above 65 years with eloquent high-grade gliomas into four groups ([years/cases] 1: 65-69/58; 2: 70-74/47; 3: 75-79/43; 4: >79/20).

Strain specific differences in vitamin D3 response: impact on gut homeostasis.

Vitamin D3 regulates a variety of biological processes irrespective of its well-known importance for calcium metabolism. Epidemiological and animal studies indicate a role in immune regulation, intestinal barrier function and microbiome diversity. Here, we analyzed the impact of different vitamin D3- containing diets on C57BL/6 and BALB/c mice, with a particular focus on gut homeostasis and also investigated effects on immune cells .

A machine learning approach for modeling the occurrence of the major intermediate hosts for schistosomiasis in East Africa.

Schistosomiasis, a prevalent water-borne disease second only to malaria, significantly impacts impoverished rural communities, primarily in Sub-Saharan Africa where over 90% of the severely affected population resides. The disease, majorly caused by Schistosoma mansoni and S. haematobium parasites, relies on freshwater snails, specifically Biomphalaria and Bulinus species, as crucial intermediate host (IH) snails.