Bridging pyrimidine hemicurcumin and Cisplatin: Synthesis, coordination chemistry, and in vitro activity assessment of a novel Pt(II) complex.

In the upcoming decades, the incidence and mortality rates of cancer are expected to rise globally, with colorectal and prostate cancers among the most prevalent types. Despite advancements in molecular targeted therapy, platinum-based chemotherapies remain the cornerstone of treatment, especially for colorectal and prostate cancer, with oxaliplatin and cisplatin being extremely effective due to their DNA-targeting capabilities. In our pursuit of new platinum-based chemotherapeutics that are potentially less toxic and more effective, we have explored the combination of the Pt-binding groups of the diaminocyclohexane ring used in oxaliplatin, with the stable amino-pyrimidine hemicurcumin moiety.

Bacterial esterases reverse lipopolysaccharide ubiquitylation to block host immunity.

Aspects of how Burkholderia escape the host's intrinsic immune response to replicate in the cell cytosol remain enigmatic. Here, we show that Burkholderia has evolved two mechanisms to block the activity of Ring finger protein 213 (RNF213)-mediated non-canonical ubiquitylation of bacterial lipopolysaccharide (LPS), thereby preventing the initiation of antibacterial autophagy. First, Burkholderia's polysaccharide capsule blocks RNF213 association with bacteria and second, the Burkholderia deubiquitylase (DUB), TssM, directly reverses the activity of RNF213 through a previously unrecognized esterase activity.

Prognostic value of tumor volume doubling time in lung-metastatic adenoid cystic carcinoma.

Objectives: Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT).

Methods: The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans.

The landscape of drug resistant absence seizures in adolescents and adults: Pathophysiology, electroclinical spectrum and treatment options.

The persistence of typical absence seizures (AS) in adolescence and adulthood may reduce the quality of life of patients with genetic generalized epilepsies (GGEs). The prevalence of drug resistant AS is probably underestimated in this patient population, and treatment options are relatively scarce. Similarly, atypical absence seizures in developmental and epileptic encephalopathies (DEEs) may be unrecognized, and often persist into adulthood despite improvement of more severe seizures.

Leveraging Google Earth Engine for a More Effective Grassland Management: A Decision Support Application Perspective.

Grasslands cover a substantial portion of the earth's surface and agricultural land and is crucial for human well-being and livestock farming. Ranchers and grassland management authorities face challenges in effectively controlling herders' grazing behavior and grassland utilization due to underdeveloped infrastructure and poor communication in pastoral areas. Cloud-based grazing management and decision support systems (DSS) are needed to address this issue, promote sustainable grassland use, and preserve their ecosystem services.

Permutation entropy-derived parameters to estimate the epileptogenic zone network.

Objective: Quantification of the epileptogenic zone network (EZN) most frequently implies analysis of seizure onset. However, important information can also be obtained from the postictal period, characterized by prominent changes in the EZN. We used permutation entropy (PE), a measure of signal complexity, to analyze the peri-ictal stereoelectroencephalography (SEEG) signal changes with emphasis on the postictal state.

Helium Optically Pumped Magnetometers Can Detect Epileptic Abnormalities as Well as SQUIDs as Shown by Intracerebral Recordings.

Magnetoencephalography based on superconducting quantum interference devices (SQUIDs) has been shown to improve the diagnosis and surgical treatment decision for presurgical evaluation of drug-resistant epilepsy. Still, its use remains limited because of several constraints such as cost, fixed helmet size, and the obligation of immobility. A new generation of sensors, optically pumped magnetometers (OPMs), could overcome these limitations.

Sleep and epilepsy: A clinical and pathophysiological overview.

The interaction between sleep and epilepsy is complex. A better understanding of the mechanisms linking sleep and epilepsy appears increasingly important as it may improve diagnosis and therapeutic strategies in patients with epilepsy. In this narrative review, we aim to (i) provide an overview of the physiological and pathophysiological processes linking sleep and epilepsy; (ii) present common sleep disorders in patients with epilepsy; (iii) discuss how sleep and sleep disorders should be considered in new therapeutic approaches to epilepsy such as neurostimulation; and (iv) present the overall nocturnal manifestations and differential diagnosis between epileptic seizures and parasomnia.

Dedicated bacterial esterases reverse lipopolysaccharide ubiquitylation to block immune sensing.

Pathogenic bacteria have evolved diverse mechanisms to counteract cell-autonomous immunity, which otherwise guards both immune and non-immune cells from the onset of an infection. The versatile immunity protein Ring finger protein 213 (RNF213) mediates the non-canonical ester-linked ubiquitylation of lipopolysaccharide (LPS), marking bacteria that sporadically enter the cytosol for destruction by antibacterial autophagy. However, whether cytosol-adapted pathogens are ubiquitylated on their LPS and whether they escape RNF213-mediated immunity, remains unknown.

Robotic monitoring of grasslands: a dataset from the EU Natura2000 habitat 6210* in the central Apennines (Italy).

Despite the remarkable growth of the global market for robotics, robotic monitoring of habitats is still an understudied topic. This is true, among others, for the species-rich EU Annex I habitat "6210 - Semi-natural grasslands and scrubland facies on calcareous substrates". This habitat is typically surveyed by human operators.

Spontaneous fast-ultradian dynamics of polymorphic interictal events in drug-resistant focal epilepsy.

Objective: We studied the rate dynamics of interictal events occurring over fast-ultradian time scales, as commonly examined in clinics to guide surgical planning in epilepsy.

Methods: Stereo-electroencephalography (SEEG) traces of 35 patients with good surgical outcome (Engel I) were analyzed. For this we developed a general data mining method aimed at clustering the plethora of transient waveform shapes including interictal epileptiform discharges (IEDs) and assessed the temporal fluctuations in the capability of mapping the epileptogenic zone (EZ) of each type of event.

New and emerging drugs for the treatment of advanced cutaneous squamous cell carcinoma.

Introduction: Cutaneous squamous cell carcinoma (CSCC) is the second most common form of human cancer. Treatment of locally advanced and/or recurrent CSCC is often challenging. A subset of patients are not candidates for curative-intent therapies due to extent of loco-regional disease, refractoriness to prior local therapy, or presence of distant metastasis.

Comparison of beamformer and ICA for dynamic connectivity analysis: A simultaneous MEG-SEEG study.

Magnetoencephalography (MEG) is a powerful tool for estimating brain connectivity with both good spatial and temporal resolution. It is particularly helpful in epilepsy to characterize non-invasively the epileptic networks. However, using MEG to map brain networks requires solving a difficult inverse problem that introduces uncertainty in the activity localization and connectivity measures.

Characteristics and Neural Correlates of Emotional Behavior during Prefrontal Seizures.

Objective: This study was undertaken to characterize clinical expression and intracerebral electroencephalographic (EEG) correlates of emotional expression during prefrontal epileptic seizures.

Methods: We performed a descriptive analysis of seizure semiology in patients explored with stereo-EEG (SEEG) for pharmacoresistant prefrontal epilepsy, using a semiquantitative score for seizure-related emotional behavior. Two independent observers scored occurrence and intensity of objective emotional features (face/body movements/vocalization/overall appearance), testing interobserver reliability.

Cathepsin S Levels and Survival Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

Background: Patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are at high residual risk for long-term cardiovascular (CV) mortality. Cathepsin S (CTSS) is a lysosomal cysteine protease with elastolytic and collagenolytic activity that has been involved in atherosclerotic plaque rupture.

Objectives: The purpose of this study was to determine the following: 1) the prognostic value of circulating CTSS measured at patient admission for long-term mortality in NSTE-ACS; and 2) its additive value over the GRACE (Global Registry of Acute Coronary Events) risk score.

Beta-Secretase-1 Antisense RNA Is Associated with Vascular Ageing and Atherosclerotic Cardiovascular Disease.

Background:  The noncoding antisense transcript for β-secretase-1 () is a long noncoding RNA with a pivotal role in the regulation of amyloid-β (Aβ). We aimed to explore the clinical value of expression in atherosclerotic cardiovascular disease (ASCVD).

Methods:  Expression of and its target, β-secretase 1 () mRNA, was measured in peripheral blood mononuclear cells derived from 434 individuals (259 without established ASCVD [non-CVD], 90 with stable coronary artery disease [CAD], and 85 with acute coronary syndrome).

Designing Organoid Models to Monitor Cancer Progression, Plasticity and Resistance: The Right Set Up for the Right Question.

The recent trend in 3D cell modeling has fostered the emergence of a wide range of models, addressing very distinct goals ranging from the fundamental exploration of cell-cell interactions to preclinical assays for personalized medicine. It is clear that no single model will recapitulate the complexity and dynamics of in vivo situations. The key is to define the critical points, achieve a specific goal and design a model where they can be validated.

Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC.

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6   6   6 m liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light.

The Role of Interstitial Fluid Pressure in Cerebral Porous Biomaterial Integration.

Recent advances in biomaterials offer new possibilities for brain tissue reconstruction. Biocompatibility, provision of cell adhesion motives and mechanical properties are among the present main design criteria. We here propose a radically new and potentially major element determining biointegration of porous biomaterials: the favorable effect of interstitial fluid pressure (IFP).

rhamnolipid micelles deliver toxic metabolites and antibiotics into .

Efficient delivery of toxic compounds to bacterial competitors is essential during interspecies microbial warfare. Rhamnolipids (RLPs) are glycolipids produced by and species involved in solubilization and uptake of environmental aliphatic hydrocarbons and perform as biosurfactants for swarming motility. Here, we show that RLPs produced by associate to form micelles.

Adenosine-to-inosine RNA editing contributes to type I interferon responses in systemic sclerosis.

Objective: Adenosine deaminase acting on RNA-1 (ADAR1) enzyme is a type I interferon (IFN)-stimulated gene (ISG) catalyzing the deamination of adenosine-to-inosine, a process called A-to-I RNA editing. A-to-I RNA editing takes place mainly in Alu elements comprising a primate-specific level of post-transcriptional gene regulation. Whether RNA editing is involved in type I IFN responses in systemic sclerosis (SSc) patients remains unknown.

Cryogel-based Injectable 3D Microcarrier Co-culture for Support of Hematopoietic Progenitor Niches.

Although hematopoietic stem cell (HSC) transplantation can restore functional hematopoiesis upon immune or chemotherapy-induced bone marrow failure, complications often arise during recovery, leading to up to 25% transplant-related mortality in treated patients. In hematopoietic homeostasis and regeneration, HSCs in the bone marrow give rise to the entirety of cellular blood components. One of the challenges in studying hematopoiesis is the ability to successfully mimic the relationship between the stroma and hematopoietic stem and progenitor cells (HSPCs).