Opposing effects of mycotoxins alternariol and deoxynivalenol on the immunomodulatory effects of oxaliplatin and triapine.

Mycotoxin occurrence in food worldwide is estimated to increase due to climate change. Moreover, studies on how these food contaminants interfere with medications and especially anticancer therapies are rare. With the rise of anticancer immunotherapies, particularly mycotoxins with immunomodulatory activity, such as alternariol (AOH) or deoxynivalenol (DON), are of great concern.

Automatic Image Registration Provides Superior Accuracy Compared with Surface Matching in Cranial Navigation.

Objective: The precision of neuronavigation systems relies on the correct registration of the patient's position in space and aligning it with radiological 3D imaging data. Registration is usually performed by the acquisition of anatomical landmarks or surface matching based on facial features. Another possibility is automatic image registration using intraoperative imaging.

Chemical composition of anti-microbially active fractions derived from extract of filamentous fungus Keratinophyton Lemmensii including three novel bioactive compounds.

Screening for new bioactive microbial metabolites, we found a novel okaramine derivative, for which we propose the trivial name lemmokaramine, as well as two already known okaramine congeners - okaramine H and okaramine J - responsible for antimicrobial activity of the recently described microscopic filamentous fungus, Keratinophyton lemmensii BiMM-F76 (= CCF 6359). In addition, two novel substances, a new cyclohexyl denominated lemmensihexol and a new tetrahydroxypyrane denominated lemmensipyrane, were purified and characterized. The compounds were isolated from the culture extract of the fungus grown on modified yeast extract sucrose medium by means of flash chromatography followed by preparative HPLC.

Transparent TiO nanotubes supporting silver sulfide for photoelectrochemical water splitting.

Differences between photoelectrochemical and electrochemical activity were thoroughly investigated for the oxygen evolution reaction mediated by AgS deposited on two types of ordered titania substrates. Titanium dioxide nanotubes were fabricated by anodization of magnetron sputtered Ti films on ITO-coated glass substrates or directly from Ti foil. Further, AgS deposition on the nanotubes was carried out using successive ionic layer adsorption and reaction, known as SILAR, with 5, 25, and 45 cycles performed.

Targeting PHGDH reverses the immunosuppressive phenotype of tumor-associated macrophages through α-ketoglutarate and mTORC1 signaling.

Phosphoglycerate dehydrogenase (PHGDH) has emerged as a crucial factor in macromolecule synthesis, neutralizing oxidative stress, and regulating methylation reactions in cancer cells, lymphocytes, and endothelial cells. However, the role of PHGDH in tumor-associated macrophages (TAMs) is poorly understood. Here, we found that the T helper 2 (Th2) cytokine interleukin-4 and tumor-conditioned media upregulate the expression of PHGDH in macrophages and promote immunosuppressive M2 macrophage activation and proliferation.

Automatic image registration on intraoperative CBCT compared to Surface Matching registration on preoperative CT for spinal navigation: accuracy and workflow.

Introduction: Spinal navigation solutions have been slower to develop compared to cranial ones. To facilitate greater adoption and use of spinal navigation, the relatively cumbersome registration processes need to be improved upon. This study aims to validate a new solution for automatic image registration and compare it to a traditional Surface Matching method.

Phase 2 study of add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: final results.

Ruxolitinib reduces spleen volume, improves symptoms, and increases survival in patients with intermediate- or high-risk myelofibrosis. However, suboptimal response may occur, potentially because of signaling via the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway. This phase 2 study evaluated dosing, efficacy, and safety of add-on PI3Kδ inhibitor parsaclisib for patients with primary or secondary myelofibrosis with suboptimal response to ruxolitinib.

Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health.

Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins.

Human serum albumin as a copper source for anticancer thiosemicarbazones.

Thiosemicarbazones (TSCs) are a class of biologically active compounds with promising anticancer activity. Their typical mechanism, especially of the clinically far developed representative Triapine, is chelation of iron (Fe), with the Fe-containing enzyme ribonucleotide reductase as primary intracellular target. However, for the subclass of terminally disubstituted, nanomolar-active derivatives like Dp44mT and Me2NNMe2, recent findings suggest that the chelation, stability, and reduction properties of the copper(II) (Cu) complexes are essential for their modes of action.

Degradable Bottlebrush Polypeptides and the Impact of their Architecture on Cell Uptake, Pharmacokinetics, and Biodistribution In Vivo.

Bottlebrush polymers are highly promising as unimolecular nanomedicines due to their unique control over the critical parameters of size, shape and chemical function. However, since they are prepared from biopersistent carbon backbones, most known bottlebrush polymers are non-degradable and thus unsuitable for systemic therapeutic administration. Herein, we report the design and synthesis of novel poly(organo)phosphazene-g-poly(α-glutamate) (PPz-g-PGA) bottlebrush polymers with exceptional control over their structure and molecular dimensions (Dh ≈ 15-50 nm).

Adaptation of Essential Care for Every Baby educational program to improve infant outcomes in the context of Zika.

Background: The outbreak and ongoing transmission of Zika virus provided an opportunity to strengthen essential newborn care and early childhood development systems through collaboration with the US Agency for International Development Applying Science to Strengthen and Improve Systems (USAID ASSIST). The objective was to create a system of sustainable training dissemination which improves newborn care-related quality indicators in the context of Zika.

Methods: From 2018-19, USAID ASSIST supported a series of technical assistance visits by the American Academy of Pediatrics (AAP) in four Caribbean countries to strengthen the clinical capacity in care of children potentially affected by Zika through dissemination of Essential Care for Every Baby (ECEB), teaching QI methodology, coaching visits, and development of clinical care guidelines.

Learn2Reg: Comprehensive Multi-Task Medical Image Registration Challenge, Dataset and Evaluation in the Era of Deep Learning.

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches.

Thiosemicarbazone Derivatives Developed to Overcome COTI-2 Resistance.

COTI-2 is currently being evaluated in a phase I clinical trial for the treatment of gynecological and other solid cancers. As a thiosemicarbazone, this compound contains an N,N,S-chelating moiety and is, therefore, expected to bind endogenous metal ions. However, besides zinc, the metal interaction properties of COTI-2 have not been investigated in detail so far.

Moldable and Transferrable Conductive Nanocomposites for Epidermal Electronics.

Skin-inspired soft and stretchable electronic devices based on functional nanomaterials have broad applications such as health monitoring, human-machine interface, and the Internet of things. Solution-processed conductive nanocomposites have shown great promise as a building block of soft and stretchable electronic devices. However, realizing conductive nanocomposites with high conductivity, electromechanical stability, and low modulus over a large area at sub-100 μm resolution remains challenging.

Copper-Catalyzed Glutathione Oxidation is Accelerated by the Anticancer Thiosemicarbazone Dp44mT and Further Boosted at Lower pH.

Glutathione (GSH) is the most abundant thiol in mammalian cells and plays a crucial role in maintaining redox cellular homeostasis. The thiols of two GSH molecules can be oxidized to the disulfide GSSG. The cytosolic GSH/GSSG ratio is very high (>100), and its reduction can lead to apoptosis or necrosis, which are of interest in cancer research.

A Rare Presentation of a Non-Asian Female With Metastatic Non-small-cell Lung Cancer Harboring L747P Mutation With Clinical Response to Multi-targeted Epigenetic and Inhibition.

Background: Activating mutations of the epidermal growth factor receptor (EGFR) gene have been utilized to predict the effectiveness of EGFR tyrosine kinase inhibitor (TKI) therapy. The most common EGFR mutations are exon 19 deletion and exon 21-point mutation, which are sensitive to EGFR TKI. However, rare/complex EGFR mutations still exist, data of which are scarce and controversial.

Chromatographic capture of cells to achieve single stage clarification in recombinant protein purification.

Recent advancements in cell culture engineering have allowed drug manufacturers to achieve higher productivity by driving higher product titers through cell line engineering and high-cell densities. However, these advancements have shifted the burden to clarification and downstream processing where the difficulties now revolve around removing higher levels of process- and product-related impurities. As a result, a lot of research efforts have turned to developing new approaches and technologies or process optimization to still deliver high quality biological products while controlling cost of goods.

Influence of surgical stabilization of clavicle fractures in multiply-injured patients with thoracic trauma.

Thoracic trauma has decisive influence on the outcome of multiply-injured patients and is often associated with clavicle fractures. The affected patients are prone to lung dysfunction and multiple organ failure. A multi-center, retrospective analysis of patient records documented in the TraumaRegister DGU was performed to assess the influence of surgical stabilization of clavicle fractures in patients with thoracic trauma.

Pediatric intratesticular abscess managed with a testicular sparing approach: A case report.

Intratesticular abscess is a rare finding associated with advanced or untreated epididymo-orchitis, often in immunocompromised patients. Implicated pathogens can be spread hematogenously, by urine reflux in dysfunctional voiders, through aberrant mesonephric duct anatomy, or via a patent processus vaginalis in the setting of an intra-abdominal infection. A testicular-sparing surgical approach is often used in prepubertal populations and is associated with positive outcomes.

Liposomal formulations of anticancer copper(II) thiosemicarbazone complexes.

α-N-Heterocyclic thiosemicarbazones such as triapine and COTI-2 are currently investigated as anticancer therapeutics in clinical trials. However, triapine was widely inactive against solid tumor types. A likely explanation is the short plasma half-life time and fast metabolism.

Short-term transcriptomic response to plasma membrane injury.

Plasma membrane repair mechanisms are activated within seconds post-injury to promote rapid membrane resealing in eukaryotic cells and prevent cell death. However, less is known about the regeneration phase that follows and how cells respond to injury in the short-term. Here, we provide a genome-wide study into the mRNA expression profile of MCF-7 breast cancer cells exposed to injury by digitonin, a mild non-ionic detergent that permeabilizes the plasma membrane.

Use of Patient-Reported Outcome Measures and Patient-Reported Experience Measures Within Evaluation Studies of Telemedicine Applications: Systematic Review.

Background: With the rise of digital health technologies and telemedicine, the need for evidence-based evaluation is growing. Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are recommended as an essential part of the evaluation of telemedicine. For the first time, a systematic review has been conducted to investigate the use of PROMs and PREMs in the evaluation studies of telemedicine covering all application types and medical purposes.

Structure-Activity Relationships of Triple-Action Platinum(IV) Prodrugs with Albumin-Binding Properties and Immunomodulating Ligands.

Chemotherapy with platinum complexes is essential for clinical anticancer therapy. However, due to side effects and drug resistance, further drug improvement is urgently needed. Herein, we report on triple-action platinum(IV) prodrugs, which, in addition to tumor targeting maleimide-mediated albumin binding, release the immunomodulatory ligand 1-methyl-d-tryptophan (1-MDT).

CNN-based lung CT registration with multiple anatomical constraints.

Deep-learning-based registration methods emerged as a fast alternative to conventional registration methods. However, these methods often still cannot achieve the same performance as conventional registration methods because they are either limited to small deformation or they fail to handle a superposition of large and small deformations without producing implausible deformation fields with foldings inside. In this paper, we identify important strategies of conventional registration methods for lung registration and successfully developed the deep-learning counterpart.