Intratumoral injection and retention hold promise to improve cytokine therapies for cancer.

As powerful activators of the immune system, cytokines have been extensively explored for treating various cancers. But despite encouraging advances and some drug approvals, the broad adoption of cytokine therapies in the clinic has been limited by low response rates and sometimes severe toxicities. This in part reflects an inefficient biodistribution to tumors or a pleiotropic action on bystander cells and tissues.

Meaning and prediction of 'excess mortality': a comparison of Covid-19 and pre-Covid-19 mortality data in 31 Eurostat countries from 1965 to 2021.

Determining 'excess mortality' makes it possible to compare the burden of disasters between countries and over time, and thus also to evaluate the success of mitigation measures. However, the debate on coronavirus disease 2019 (Covid-19) has exposed that calculations of excess mortalities vary considerably depending on the method and its specification. Moreover, it is often unclear what exactly is meant by 'excess mortality'.

Corrigendum: Psychometric evaluation and reference values for the German Postconcussion Symptom Inventory (PCSI-SR8) in children aged 8-12 years.

[This corrects the article DOI: 10.3389/fneur.2023.

Assessment of water, sanitation, and hygiene among women living in precarious households in a Turkish urban area.

Background: This study aimed to identify the determinants of water, sanitation, and hygiene (WASH) behaviors and conditions among women in poor neighborhoods in Izmir, Turkey, and to develop a scale for assessing WASH behaviors and conditions that is specifically designed for use in precarious urban areas.

Methods: The study used a cross-sectional design, as well as a methodological feature for developing the scale. The sample size was calculated as 243 households out of 2667 households in the Basmane neighborhood, with a 95% confidence interval and a 6% margin of error, and a woman who was responsible for cleaning was invited to participate from each household.

Knowledge through social networks: Accuracy, error, and polarisation.

This paper examines the fundamental problem of testimony. Much of what we believe to know we know in good part, or even entirely, through the testimony of others. The problem with testimony is that we often have very little on which to base estimates of the accuracy of our sources.

Psychometric evaluation and reference values for the German Postconcussion Symptom Inventory (PCSI-SR8) in children aged 8-12 years.

Background: Post-concussion symptoms (PCS) are a common consequence of pediatric traumatic brain injury (pTBI). They include cognitive, emotional, and physical disturbances. To address the lack of age-adapted instruments assessing PCS after pTBI, this study examines the psychometric properties of the German 17-item post-TBI version of the Postconcussion Symptom Inventory (PCSI-SR8) in children aged 8-12 years.

Spatial Centrosome Proteomic Profiling of Human iPSC-derived Neural Cells.

The centrosome governs many pan-cellular processes including cell division, migration, and cilium formation. However, very little is known about its cell type-specific protein composition and the sub-organellar domains where these protein interactions take place. Here, we outline a protocol for the spatial interrogation of the centrosome proteome in human cells, such as those differentiated from induced pluripotent stem cells (iPSCs), through co-immunoprecipitation of protein complexes around selected baits that are known to reside at different structural parts of the centrosome, followed by mass spectrometry.

Missense Variant in a Lagotto Romagnolo Dog with Autosomal Recessively Inherited Limb-Girdle Muscular Dystrophy.

An 8-month-old female Lagotto Romagnolo dog was presented for a 1-month history of an initial severe reluctance to move, rapidly progressing to a marked stiff gait and progressive muscular weakness and evolving to tetraparesis, which persuaded the owner to request euthanasia. A primary muscle pathology was supported by necropsy and histopathological findings. Macroscopically, the muscles were moderately atrophic, except for the diaphragm and the neck muscles, which were markedly thickened.

Lyophilization cycle design for highly concentrated protein formulations supported by micro freeze-dryer and heat flux sensor.

High-concentration protein formulations (HCPFs) represent a common strategy and freeze-drying can mitigate the stability challenges of HCPFs. In general, an in-depth characterization of the lyophilization process is essential to not impair the product quality by inappropriate process parameters. The aim of this study was to create a primary drying design space for lyophilized HCPFs by utilizing the heat flux sensor (HFS) integrated in a MicroFD with a minimum number of cycles and product vials.

Medical Management Versus Endovascular Treatment for Large-Vessel Occlusion Anterior Circulation Stroke With Low NIHSS.

Background: Endovascular treatment (EVT) for acute ischemic stroke (AIS) patients presenting with National Institutes of Health Stroke Scale score of 0 to 5 is common in clinical practice but has not yet been proven safe and effective. Our objective is to assess whether EVT on top of best medical treatment (BMT) in AIS patients with large-vessel occlusion of the anterior circulation presenting with mild symptoms is beneficial compared with BMT.

Methods: We searched MEDLINE, SCOPUS, and reference lists of retrieved articles published until December 28, 2022.

Detecting dipolarity of the geomagnetic field in the paleomagnetic record.

Recovering the geomagnetic field strength in the past is key to understanding deep Earth dynamics and detecting potential geodynamo regimes throughout the history of Earth. To better constrain the predictive power of the paleomagnetic record, we propose an approach based on the analysis of the dependency between geomagnetic field strength and inclination (angle made by the horizontal with the field lines). Based on the outcomes of statistical field models, we show that these two quantities should correlate for a wide range of Earth-like magnetic fields, even with enhanced secular variation, persistent nonzonal components, and severe noise contamination.

Non-cell-autonomous regulation of interneuron specification mediated by extracellular vesicles.

Disruption in neurogenesis and neuronal migration can influence the assembly of cortical circuits, affecting the excitatory-inhibitory balance and resulting in neurodevelopmental and neuropsychiatric disorders. Using ventral cerebral organoids and dorsoventral cerebral assembloids with mutations in the extracellular matrix gene , we show that extracellular vesicles released into the extracellular environment regulate the molecular differentiation of neurons, resulting in alterations in migratory dynamics. To investigate how extracellular vesicles affect neuronal specification and migration dynamics, we collected extracellular vesicles from ventral cerebral organoids carrying a mutation in , previously identified in individuals with cortical malformations and neuropsychiatric disorders.

Chemometrics in Protein Formulation: Stability Governed by Repulsion and Protein Unfolding.

Therapeutic proteins can be challenging to develop due to their complexity and the requirement of an acceptable formulation to ensure patient safety and efficacy. To date, there is no universal formulation development strategy that can identify optimal formulation conditions for all types of proteins in a fast and reliable manner. In this work, high-throughput characterization, employing a toolbox of five techniques, was performed on 14 structurally different proteins formulated in 6 different buffer conditions and in the presence of 4 different excipients.

Comparing x-ray phase-contrast imaging using a Talbot array illuminator to propagation-based imaging for non-homogeneous biomedical samples.

Phase-contrast computed tomography can visualize soft tissue samples with high contrast. At coherent sources, propagation-based imaging (PBI) techniques are among the most common, as they are easy to implement and produce high-resolution images. Their downside is a low degree of quantitative data due to simplifying assumptions of the sample properties in the reconstruction.

Preclinical Assessment of Tissue Effects by Gastrointestinal Endoscope Tip Temperature.

Background: Endoscope tips are heated by their electrical and illuminating components. During the procedure, they might get in close or even direct contact with intestinal tissues.

Objective: To assess endoscope tip and tissue temperature as well as histopathologic changes of gastrointestinal (GI) tissues when exposed to the heated tip of GI endoscopes.

Disorder-Induced Topological State Transition in the Optical Skyrmion Family.

Skyrmions endowed with topological protection have been extensively investigated in various platforms including magnetics, ferroelectrics, and liquid crystals, stimulating applications such as memories, logic devices, and neuromorphic computing. While the optical counterpart has been proposed and realized recently, the study of optical skyrmions is still in its infancy. Among the unexplored questions, the investigation of the topology induced robustness against disorder is of substantial importance on both fundamental and practical sides but remains elusive.

Met/HGFR triggers detrimental reactive microglia in TBI.

The complexity of signaling events and cellular responses unfolding in neuronal, glial, and immune cells upon traumatic brain injury (TBI) constitutes an obstacle in elucidating pathophysiological links and targets for intervention. We use array phosphoproteomics in a murine mild blunt TBI to reconstruct the temporal dynamics of tyrosine-kinase signaling in TBI and then scrutinize the large-scale effects of perturbation of Met/HGFR, VEGFR1, and Btk signaling by small molecules. We show Met/HGFR as a selective modifier of early microglial response and that Met/HGFR blockade prevents the induction of microglial inflammatory mediators, of reactive microglia morphology, and TBI-associated responses in neurons and vasculature.

Iron-induced cytotoxicity mediated by endolysosomal TRPML1 channels is reverted by TFEB.

Increased brain iron content has been consistently reported in sporadic Parkinson's disease (PD) patients, and an increase in cytosolic free iron is known to cause oxidative stress and cell death. However, whether iron also accumulates in susceptible brain areas in humans or in mouse models of familial PD remains unknown. In addition, whilst the lysosome functions as a critical intracellular iron storage organelle, little is known about the mechanisms underlying lysosomal iron release and how this process is influenced by lysosome biogenesis and/or lysosomal exocytosis.

Sparse inference and active learning of stochastic differential equations from data.

Automatic machine learning of empirical models from experimental data has recently become possible as a result of increased availability of computational power and dedicated algorithms. Despite the successes of non-parametric inference and neural-network-based inference for empirical modelling, a physical interpretation of the results often remains challenging. Here, we focus on direct inference of governing differential equations from data, which can be formulated as a linear inverse problem.

Apolipoprotein L1 (APOL1) cation current in HEK-293 cells and in human podocytes.

Two heterozygous missense variants (G1 and G2) of Apolipoprotein L1 (APOL1) found in individuals of recent African ancestry can attenuate the severity of infection by some forms of Trypanosoma brucei. However, these two variants within a broader African haplotype also increase the risk of kidney disease in Americans of African descent. Although overexpression of either variant G1 or G2 causes multiple pathogenic changes in cultured cells and transgenic mouse models, the mechanism(s) promoting kidney disease remain unclear.

Systematic assessment of the replicability and generalizability of preclinical findings: Impact of protocol harmonization across laboratory sites.

The influence of protocol standardization between laboratories on their replicability of preclinical results has not been addressed in a systematic way. While standardization is considered good research practice as a means to control for undesired external noise (i.e.