Extracellular vesicles promote migration despite BRAF inhibitor treatment in malignant melanoma cells.

Extracellular vesicles (EVs) constitute a vital component of intercellular communication, exerting significant influence on metastasis formation and drug resistance mechanisms. Malignant melanoma (MM) is one of the deadliest forms of skin cancers, because of its high metastatic potential and often acquired resistance to oncotherapies. The prevalence of BRAF mutations in MM underscores the importance of BRAF-targeted therapies, such as vemurafenib and dabrafenib, alone or in combination with the MEK inhibitor, trametinib.

The predictive validity of the V-RISK-10 and BVC among involuntarily admitted patients.

Although endangerment towards others is a criterion for an involuntary admission in many countries, research on risk assessment of endangerment among involuntarily admitted individuals is limited. In this retrospective case-control study, we calculated scores for a German-translated version of the Violence Risk Screening-10 (V-RISK-10) and the Brøset Violence Checklist (BVC) in a sample of 111 people undergoing an involuntary admission in Reinickendorf, Berlin. Outcomes were violence, coercive measures, and readmission.

NnU-Net versus mesh growing algorithm as a tool for the robust and timely segmentation of neurosurgical 3D images in contrast-enhanced T1 MRI scans.

Purpose: This study evaluates the nnU-Net for segmenting brain, skin, tumors, and ventricles in contrast-enhanced T1 (T1CE) images, benchmarking it against an established mesh growing algorithm (MGA).

Methods: We used 67 retrospectively collected annotated single-center T1CE brain scans for training models for brain, skin, tumor, and ventricle segmentation. An additional 32 scans from two centers were used test performance compared to that of the MGA.

Mediterranean vineyards and olive groves in Croatia harbour some rare and endemic invertebrates.

The Mediterranean is characterised by high biodiversity and numerous endemic species. These species are not only present in natural habitats, but also inhabit areas under human influence, such as agricultural lands. In the biodiversity assessment of Mediterranean vineyards and olive orchards within Zadar County, in Croatia, we identified eight endemic species with Mediterranean distribution, six with a Balkan Peninsula distribution, four with Dinaric Alps distribution and three species rare and endangered in Europe.

Evaluation Metrics for Augmented Reality in Neurosurgical Preoperative Planning, Surgical Navigation, and Surgical Treatment Guidance: A Systematic Review.

Background And Objective: Recent years have shown an advancement in the development of augmented reality (AR) technologies for preoperative visualization, surgical navigation, and intraoperative guidance for neurosurgery. However, proving added value for AR in clinical practice is challenging, partly because of a lack of standardized evaluation metrics. We performed a systematic review to provide an overview of the reported evaluation metrics for AR technologies in neurosurgical practice and to establish a foundation for assessment and comparison of such technologies.

Application of virtual and mixed reality for 3D visualization in intracranial aneurysm surgery planning: a systematic review.

Background: Precise preoperative anatomical visualization and understanding of an intracranial aneurysm (IA) are fundamental for surgical planning and increased intraoperative confidence. Application of virtual reality (VR) and mixed reality (MR), thus three-dimensional (3D) visualization of IAs could be significant in surgical planning. Authors provide an up-to-date overview of VR and MR applied to IA surgery, with specific focus on tailoring of the surgical treatment.

Effect of Intraoperative Mixed-Reality use on Nonsurgical Team Members in the Neurosurgical Operating Room: An Explorative Study.

Objectives: Mixed-reality (MxR) implementation in the neurosurgical operating room (OR) is emerging, but the impact of this technology on the nonsurgical OR staff has not been investigated yet. The purpose of this study is to evaluate the nonsurgical OR team's perception of the impact of intraoperative MxR use.

Methods: The evaluation occurred in a neurosurgical institution implementing MxR perioperatively on a daily basis for 15 months.

Clinicopathological and survival features of neuroendocrine tumors: A retrospective analysis of 153 cases, our current remarks on a heterogeneous tumor group, and still unmet future expectations.

Objective: Neuroendocrine neoplasms (NENs) originate from the diffuse neuroendocrine cell system and constitute a heterogeneous group of tumors exhibiting diverse clinical and biological characteristics. NENs include well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). In the present study, we performed a retrospective analysis of patients diagnosed with NET to evaluate clinicopathological characteristics, treatment and outcomes.

A PDE10A inhibitor CPL500036 is a novel agent modulating striatal function devoid of most neuroleptic side-effects.

Phosphodiesterase 10A (PDE10A) is expressed almost exclusively in the striatum and its inhibition is suggested to offer potential treatment in disorders associated with basal ganglia. We evaluated the selectivity, cytotoxicity, genotoxicity, pharmacokinetics and potential adverse effects of a novel PDE10A inhibitor, CPL500036, . The potency of CPL500036 was demonstrated by microfluidic technology, and selectivity was investigated in a radioligand binding assay against 44 targets.

Measurement System for Piezoelectric Resonance Impedance Spectroscopy Under Combined AC and High-Voltage DC Loading.

Piezoelectric resonance impedance spectroscopy is a standardized measurement technique for determining the electromechanical, elastic, and dielectric parameters of piezoceramics. However, commercial measurement setups are designed for small-signal measurements and encounter difficulties when constant driving voltages/currents are required at resonances, higher fields, or combined AC and DC loading. The latter is particularly important to evaluate the DC bias-hardening effect of piezoelectrics.

Effect of Different Watering Regimes on Olive Oil Quality and Composition of Coratina Cultivar Olives Grown on Karst Soil in Croatia.

Croatian islands are olive growing areas characterized by poor conditions for olive trees because of karst soil and a precipitation deficiency. Under these conditions, irrigation is a very important factor for constant olive oil production. This paper aims to investigate the effects of different watering regimes on quantity, sensory and chemical quality and composition of Coratina cv.

Risk Assessment and Area-Wide Crop Rotation to Keep Western Corn Rootworm below Damage Thresholds and Avoid Insecticide Use in European Maize Production.

The Western corn rootworm (WCR), LeConte, has been a serious quarantine pest to maize in Europe since the mid-1990s. The integrated pest management of WCR requires an accurate knowledge of the factors that contribute most to risks of crop damage, as well as knowledge of effective area-wide strategies based on agronomic measures, such as crop rotation. In Italy and Croatia, agronomic and cultural factors in fields damaged by WCR were evaluated through a long-term survey.

Teachers perception of the use on a low-cost pulse rate sensor for biology education.

Information and Communication Technology (ICT) is a commonly used concept in schools, implemented in laboratory work in the form of various digital devices. We evaluated the ICT implementation in cardiovascular physiology in Slovenian primary school education. Surprisingly, we showed a relatively low acceptance rate in biology classes: only 42.

Microsimulation based quantitative analysis of COVID-19 management strategies.

Pandemic management requires reliable and efficient dynamical simulation to predict and control disease spreading. The COVID-19 (SARS-CoV-2) pandemic is mitigated by several non-pharmaceutical interventions, but it is hard to predict which of these are the most effective for a given population. We developed the computationally effective and scalable, agent-based microsimulation framework PanSim, allowing us to test control measures in multiple infection waves caused by the spread of a new virus variant in a city-sized societal environment using a unified framework fitted to realistic data.

Structure-Based Design and Optimization of FPPQ, a Dual-Acting 5-HT and 5-HT Receptor Antagonist with Antipsychotic and Procognitive Properties.

In line with recent clinical trials demonstrating that ondansetron, a 5-HT receptor (5-HTR) antagonist, ameliorates cognitive deficits of schizophrenia and the known procognitive effects of 5-HT receptor (5-HTR) antagonists, we applied the hybridization strategy to design dual-acting 5-HT/5-HTR antagonists. We identified the first-in-class compound , which behaves as a 5-HTR antagonist and a neutral antagonist 5-HTR of the Gs pathway. shows selectivity over 87 targets and decent brain penetration.

Cannabidiol Improves Cognitive Impairment and Reverses Cortical Transcriptional Changes Induced by Ketamine, in Schizophrenia-Like Model in Rats.

Cannabidiol (CBD), a non-psychotropic cannabinoid, demonstrates antipsychotic-like and procognitive activities in humans and in animal models of schizophrenia. The mechanisms of these beneficial effects of CBD are unknown. Here, we examined behavioral effects of CBD in a pharmacological model of schizophrenia-like cognitive deficits induced by repeated ketamine (KET) administration.

The development of the ICIQ-UAB: A patient reported outcome measure for underactive bladder.

Aims: To present the development of the International Consultation on Incontinence Questionnaire-underactive bladder (ICIQ-UAB) as the first patient reported outcome measure for the assessment of the symptoms and impact on the health-related quality of life of UAB developed in-line with the Food and Drug Administration Guidance for Industry.

Methods: Draft items were developed following 44 semi-structured concept elicitation interviews in the UK and refined using 36 cognitive interviews. A pilot study was designed to assess the draft ICIQ-UAB's initial psychometric properties with 54 patients recruited from European hospitals.

What are the additional signs and symptoms in patients with detrusor underactivity and coexisting detrusor overactivity?

Aims: This study aimed to determine what difference the inclusion of patients with coexisting detrusor overactivity (DO) makes to the signs and symptoms of patients with detrusor underactivity (DU).

Methods: A total of 250 male and 435 female urodynamic tests were analyzed retrospectively. Signs and symptoms which showed a statistically significant difference between DU without DO and DU with DO were identified.

Novel multi-target azinesulfonamides of cyclic amine derivatives as potential antipsychotics with pro-social and pro-cognitive effects.

Currently used antipsychotics are characterized by multireceptor mode of action. While antagonism of dopamine D receptors is responsible for the alleviation of "positive" symptoms of schizophrenia and the effects at other, particularly serotonergic receptors are necessary for their additional therapeutic effects, there is no consensus regarding an "ideal" target engagement. Here, a detailed SAR analysis in a series of 45 novel azinesulfonamides of cyclic amine derivatives, involving the aryl-piperazine/piperidine pharmacophore, central alicyclic amine and azinesulfonamide groups has led to the selection of (S)-4-((2-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)sulfonyl)isoquinoline (62).

Signs and symptoms that distinguish detrusor underactivity from mixed detrusor underactivity and bladder outlet obstruction in male patients.

Aims: This study aimed to identify signs and symptoms which show differences between men with detrusor underactivity (DU) compared to those with both DU and bladder outlet obstruction (BOO).

Methods: One thousand six hundred and twelve urodynamic tests on male patients were analyzed retrospectively. Signs and symptoms which showed a statistically significant difference between patients with DU alone and patients with both DU+BOO were identified.

Novel non-sulfonamide 5-HT receptor partial inverse agonist in a group of imidazo[4,5-b]pyridines with cognition enhancing properties.

A small library of novel 3H-imidazo[4,5-b]pyridine and 1H-imidazo[4,5-c]pyridine derivatives was designed and synthesized as non-sulfonamide 5-HT receptor ligands. In vitro evaluation allowed to identify compound 17 (2-ethyl-3-(3-fluorobenzyl)-7-(piperazin-1-yl)-3H-imidazo[4,5-b]pyridine) as potent 5-HT receptor partial inverse agonist in G signaling (K = 6 nM, IC = 17.6 nM).

Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, neutrophil-platelet score and prognostic nutritional index: do they have prognostic significance in metastatic pancreas cancer?

Introduction: We aimed to evaluate the prognostic significance of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), neutrophil-platelet score (NPS) and prognostic nutritional index (PNI) as proinflammatory markers in metastatic pancreas cancer (MPC).

Material And Methods: A total of 146 MPC patients followed up at our center were evaluated retrospectively for clinicopathological characteristics and hematological ratios (NLR, PLR, NPS and PNI). PNI was calculated as (10 × serum albumin [g/dL]) + (0.

Comparison of the Psychopharmacological Effects of Tiletamine and Ketamine in Rodents.

The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine (KET) produces rapid and sustained antidepressant effects in patients. Tiletamine (TIL; 2-ethylamino-2-thiophen-2-yl-cyclohexan-1-one) is another uncompetitive NMDA receptor antagonist, used in a medical (veterinary) setting as an anesthetic tranquilizer. Here, we compared the behavioral actions of KET and TIL in a variety of tests, focusing on antidepressant-like and dissociative-like effects in mice and rats.

Changes in the expression of metabotropic glutamate receptor 5 (mGluR5) in a ketamine-based animal model of schizophrenia.

It has been shown that the metabotropic glutamate receptor subtype 5 (mGluR5) is functionally associated with the NMDA subtype of the glutamate receptor family (NMDA receptors). These two receptors colocalize in brain regions associated with schizophrenia. Although the role of the NMDA receptor in cognitive and negative symptoms of schizophrenia is well studied, information about the role of mGluR5 receptors in schizophrenia is sparse.

Novel 5-HTR antagonists, arylsulfonamide derivatives of (aryloxy)propyl piperidines: Add-on effect to the antidepressant activity of SSRI and DRI, and pro-cognitive profile.

A novel series of arylsulfonamide derivatives of (aryloxy)propyl piperidines was designed to obtain potent 5-HTR antagonists. Among the compounds evaluated herein, 3-chloro-N-{1-[3-(1,1-biphenyl-2-yloxy)2-hydroxypropyl]piperidin-4-yl}benzenesulfonamide (25) exhibited antagonistic properties at 5-HTR and showed selectivity over selected serotoninergic and dopaminergic receptors, as well as over serotonin, noradrenaline and dopamine transporters. Compound 25 demonstrated significant antidepressant-like activity in the forced swim test (0.