Combination CXCR4 and PD1 blockade enhances intratumoral dendritic cell activation and immune responses against hepatocellular carcinoma.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of unresectable hepatocellular carcinoma (HCC), but their impressive efficacy is seen in just a fraction of patients. One key mechanism of immunotherapy resistance is the paucity of dendritic cells (DCs) in liver malignancies. Here, we tested combination blockade of programmed death receptor 1 (PD1) and CXCR4, a receptor for CXCL12, a pleiotropic factor that mediates immunosuppression in tumors.

Safety and feasibility of home-based transcranial alternating current stimulation in youths with 22q11.2 deletion syndrome.

Unlabelled: Neurodevelopmental disorders such as attention deficit and/or hyperactivity disorder (ADHD) and schizophrenia are characterized by core impairment in executive functions (EF). Despite the development of various behavioral interventions to enhance EF, the evidence is still scarce. Alternatively, non-invasive brain stimulation tools such as transcranial alternating current stimulation (tACS) has emerged as a potential strategy to alleviate cognitive deficits.

Syphilis in pregnant women and congenital syphilis from 2012 to 2021 in Switzerland: a multicentre, retrospective study.

Background And Aims Of The Study: Congenital syphilis is a rare complication of syphilis in pregnant women. Vertical transmission may occur at any time during pregnancy. The incidence of congenital syphilis has been increasing worldwide.

Inadequate health literacy and higher healthcare utilisation among older adults in Switzerland: cross-sectional evidence from a population-based study.

Background And Aim: Population ageing in Switzerland poses significant challenges, including for the healthcare system. Inadequate health literacy can hinder individuals' ability to seek appropriate treatments and navigate the healthcare system efficiently. This study explores the associations between health literacy and the number of consultations with general practitioners and healthcare specialists in a population-based sample of adults aged 58+ in Switzerland.

Rebalance the Inhibitory System in the Elderly Brain: Influence of Balance Learning on GABAergic Inhibition and Functional Connectivity.

Aging involves complex processes that impact the structure, function, and metabolism of the human brain. Declines in both structural and functional integrity along with reduced local inhibitory tone in the motor areas, as indicated by reduced γ-aminobutyric acid (GABA) levels, are often associated with compromised motor performance in elderly adults. Using multimodal neuroimaging techniques including magnetic resonance spectroscopy (MRS), diffusion magnetic resonance imaging (MRI), functional MRI as well as transcranial magnetic stimulation to assess short-interval intracortical inhibition (SICI), this study explores whether these age-related changes can be mitigated by motor learning.

Efficacy and Safety of Dolutegravir Plus Emtricitabine vs Combined Antiretroviral Therapy for the Maintenance of HIV Suppression: Results Through Week 144 of the SIMPL'HIV Trial.

The SIMPL'HIV study investigated whether switching to dolutegravir (DTG) + emtricitabine (FTC) was noninferior to continuing combined antiretroviral therapy for maintaining HIV-1 suppression at 144 weeks. The study demonstrated that viral suppression, CD4 gains, adverse events, quality of life, and patient satisfaction were comparable between groups, confirming DTG + FTC's safety and efficacy for long-term management of HIV-1 infection.

A multicellular developmental program in a close animal relative.

All animals develop from a single-celled zygote into a complex multicellular organism through a series of precisely orchestrated processes. Despite the remarkable conservation of early embryogenesis across animals, the evolutionary origins of how and when this process first emerged remain elusive. Here, by combining time-resolved imaging and transcriptomic profiling, we show that single cells of the ichthyosporean Chromosphaera perkinsii-a close relative that diverged from animals about 1 billion years ago-undergo symmetry breaking and develop through cleavage divisions to produce a prolonged multicellular colony with distinct co-existing cell types.

Cytosolic dependent translation supports mitochondrial RNA processing.

Mitochondrial biogenesis relies on both the nuclear and mitochondrial genomes, and imbalance in their expression can lead to inborn errors of metabolism, inflammation, and aging. Here, we investigate N6AMT1, a nucleo-cytosolic methyltransferase that exhibits genetic codependency with mitochondria. We determine transcriptional and translational profiles of and report that it is required for the cytosolic translation of TRMT10C (MRPP1) and PRORP (MRPP3), two subunits of the mitochondrial RNAse P enzyme.

Very early symptomatic metastasis pseudoprogression after stereotactic brain radiosurgery in a melanoma patient treated with BRAF/MEK inhibitors: a case report and review of the literature.

Introduction: Significant therapeutic changes have recently occurred in the management of melanoma brain metastases (BMs), both in the field of local treatments, with the rise of stereotactic radiotherapy (RT), as well as in systemic ones, with the advent of immunotherapy and targeted therapies (TT). These advances have brought about new challenges, particularly regarding the potential interactions between new TT (notably BRAF/MEK inhibitors) and irradiation. Through a clinical case, we will discuss a side effect not previously described in the literature: ultra-early pseudoprogression (PP) following brain stereotactic radiosurgery (SRS), in a patient treated with dabrafenib-trametinib.

Community-based reconstruction and simulation of a full-scale model of the rat hippocampus CA1 region.

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system.

Projecting Untruncated Climate Change Effects on Species' Climate Suitability: Insights From an Alpine Country.

Climate projections for continental Europe indicate drier summers, increased annual precipitation, and less snowy winters, which are expected to cause shifts in species' distributions. Yet, most regions/countries currently lack comprehensive climate-driven biodiversity projections across taxonomic groups, challenging effective conservation efforts. To address this gap, our study evaluated the potential effects of climate change on the biodiversity of an alpine country of Europe, Switzerland.

Can ChatGPT Provide Useful Guidance to Assess the Current State of and Future Priorities for Aging Research in the Social Sciences?

The multifaceted implications of global population aging require regular assessments of the current state of aging-related social science research and the identification of potential future research priorities in this important area. Given the multi-, inter-, and transdisciplinary nature of this field, such assessments typically require the involvement of experts from diverse backgrounds to ensure a comprehensive picture and to synthesize understudied and newly emerging topics into a future research agenda. We explored to what extent ChatGPT (version GPT-4, OpenAI) might be a useful tool for synthesizing the current state of research and identifying promising future research areas, which could feed into expert panel discussions for priority setting.

Subaxial cervical foraminal chondromas: case-based discussion on surgical management.

Cervical foraminal chondromas are benign lesions that may require surgical resection when symptomatic due to radicular and/or spinal cord compression. The aim of surgery is to achieve gross tumor removal while preserving neurological function and spine stability. The authors describe a case of subaxial foraminal chondroma with a systematic review of the literature on patients with cervical chondromas.

Electron-Beam Writing of Atomic-Scale Reconstructions at Oxide Interfaces.

The epitaxial growth of complex oxides enables the production of high-quality films, yet substrate choice is restricted to certain symmetry and lattice parameters, thereby limiting the technological applications of epitaxial oxides. In comparison, the development of free-standing oxide membranes gives opportunities to create novel heterostructures by nonepitaxial stacking of membranes, opening new possibilities for materials design. Here, we introduce a method for writing, with atomic precision, ionically bonded crystalline materials across the gap between an oxide membrane and a carrier substrate.

Calcite precipitation: The forgotten piece of lakes' carbon cycle.

Lakes emit substantial amounts of carbon dioxide (CO) into the atmosphere, but why they do remains debated. The long-standing vision of lakes as solely respirators of the organic matter leaking from the soils has been challenged by evidence that inorganic carbon produced by weathering of the catchment bedrock could also support lake CO emissions. How inorganic carbon inputs ultimately generate lake CO outgassing remains a blind spot.

Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans.

Because of the depth of the hippocampal-entorhinal complex (HC-EC) in the brain, understanding of its role in spatial navigation via neuromodulation was limited in humans. Here, we aimed to better elucidate this relationship in healthy volunteers, using transcranial temporal interference electric stimulation (tTIS), a noninvasive technique allowing to selectively neuromodulate deep brain structures. We applied tTIS to the right HC-EC in either continuous or intermittent theta-burst stimulation patterns (cTBS or iTBS), compared to a control condition, during a virtual reality-based spatial navigation task and concomitant functional magnetic resonance imaging.

Association of mid-regional pro-adrenomedullin with office and 24-h ambulatory blood pressure in a Swiss general population sample.

Objective: Adrenomedullin (ADM) is a potent vasodilator. The association between plasma ADM levels and blood pressure (BP) remains unclear. We assessed the association between mid-regional-pro-ADM (MR-proADM) and BP in a multicenter population- and family-based cohort.

Dissecting the Membrane Association Mechanism of Aerolysin Pores at Femtomolar Concentrations Using Water as a Probe.

Aerolysin is a bacterial toxin that forms transmembrane pores at the host plasma membrane and has a narrow internal diameter and great stability. These assets make it a highly promising nanopore for detecting biopolymers such as nucleic acids and peptides. Although much is known about aerolysin from a microbiological and structural perspective, its membrane association and pore-formation mechanism are not yet fully understood.

Driver or passenger? Use of a Bayesian network for the evaluation of DNA results in a fatal car accident.

This article presents a case where the issue was to determine who was the driver and who was the passenger at the time of a fatal car accident involving two persons, one of whom died in the accident. The presence of the two persons in the car was not contested, only the mechanisms that led to the deposition of the DNA (i.e.

Diabetes and the risk of cardiovascular events and all-cause mortality among older adults: an individual participant data analysis of five prospective studies.

Background: Guidelines and studies provide conflicting information on whether type 2 diabetes (T2D) should be considered a coronary heart disease risk (CHD) equivalent in older adults.

Methods: We synthesized participant-level data on 82,723 individuals aged ≥65 years from five prospective studies in two-stage meta-analyses. We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D (presence versus absence) on a primary composite outcome defined as cardiovascular events or all-cause mortality.

Making Conscientious Decisions: Engaging in Venous Leg Ulcer Self-Management Following Nurse-Led Patient Education.

Venous leg ulcers (VLUs) provoke multiple symptoms and impact individuals and society as a whole. Their treatment and prevention strategies require individual's involvement in self-management strategies. Insufficient knowledge with regard to prevention, management, and treatment has been identified as a critical factor related to VLUs and their recurrence.