The Prostaglandin EP4 Antagonist Vorbipiprant Combined with PD-1 Blockade for Refractory Microsatellite Stable Metastatic Colorectal Cancer: A Phase 1b/2a Trial.

Purpose: Novel combinations are required to overcome resistance to immune checkpoint inhibitors (ICIs) in proficient mismatch repair (pMMR) or microsatellite stable (MSS) metastatic colorectal cancer (mCRC). We aimed to determine whether vorbipiprant, a prostaglandin EP4 receptor antagonist, can convert immune-resistant mCRC into a tumor responsive to anti-PD-1 inhibition.

Patients And Methods: This phase 1b/2a prospective, open-label, single-arm trial followed a 3 + 3 dose escalation and dose optimization design.

Hybrid biofabricated blood vessel for medical devices testing.

Current and tests applied to assess the safety of medical devices retain several limitations, such as an incomplete ability to faithfully recapitulate human features, and to predict the response of human tissues together with non-trivial ethical aspects. We here challenged a new hybrid biofabrication technique that combines bioprinting and Fast Diffusion-induced Gelation strategy to generate a vessel-like structure with the attempt to spatially organize fibroblasts, smooth-muscle cells, and endothelial cells. The introduction of Fast Diffusion-induced Gelation minimizes the endothelial cell mortality during biofabrication and produce a thin endothelial layer with tunable thickness.

Model-driven engineering for digital twins: a graph model-based patient simulation application.

Introduction: Digital twins of patients are virtual models that can create a digital patient replica to test clinical interventions without exposing real patients to risk. With the increasing availability of electronic health records and sensor-derived patient data, digital twins offer significant potential for applications in the healthcare sector.

Methods: This article presents a scalable full-stack architecture for a patient simulation application driven by graph-based models.

Leveraging social media for resident training in developing countries: A case study of Libya.

Social media platforms have emerged as invaluable tools for remote training in resource-constrained countries. This study presents the development, implementation, and preliminary assessment of a remote intensive care unit (ICU) training program conducted in Libya utilizing social media platforms. This educational initiative was based on the Checklist for Early Recognition and Treatment of Acute Illness and iNjury (CERTAIN) program, targeting Libyan resident physicians.

Development and validation of a preliminary multivariable diagnostic model for identifying unusual infections in hospitalized patients.

Diagnostic delay leads to poor outcomes in infections, and it occurs more often when the causative agent is unusual. Delays are attributable to failing to consider such diagnoses in a timely fashion. Using routinely collected electronic health record (EHR) data, we built a preliminary multivariable diagnostic model for early identification of unusual fungal infections and tuberculosis in hospitalized patients.

Centralized Multipatient Dashboards' Impact on Intensive Care Unit Clinician Performance and Satisfaction: A Systematic Review.

Background:  Intensive care unit (ICU) clinicians encounter frequent challenges with managing vast amounts of fragmented data while caring for multiple critically ill patients simultaneously. This may lead to increased provider cognitive load that may jeopardize patient safety.

Objectives:  This systematic review assesses the impact of centralized multipatient dashboards on ICU clinician performance, perceptions regarding the use of these tools, and patient outcomes.

Ferulated Poly(vinyl alcohol) based hydrogels.

New graft copolymers were prepared by reaction of poly (vinyl alcohol) (PVA) with mono-imidazolide or bis-imidazolide derivatives of ferulic acid (FA) with the formation of ester bonds. The obtained graft copolymers, thanks to the crosslinking capability of FA, formed in water strong gels as verified by rheological analyses. The resulting hydrogels were characterized to evaluate their applicability as wound dressing.

Endoscopic Ultrasound to Identify the Actual Cause of Idiopathic Acute Pancreatitis: A Systematic Review.

Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive diagnostic evaluation. Endoscopic ultrasound (EUS) has emerged as a valuable tool in the diagnostic workup of IAP. This review explores the pivotal role of EUS in detecting the actual cause of IAP and assessing its accuracy, timing, safety, and future technological improvement.

EXPLORING THE ROLE OF CENTRAL VENOUS OXYGEN SATURATION IN THE EVALUATION AND MANAGEMENT OF SEVERE HYPOXEMIA IN MECHANICALLY VENTILATED PATIENTS.

Background: Although central venous oxygen saturation (ScvO 2 ) has been used as an endpoint for the treatment of circulatory shock, its role in guiding the evaluation and treatment of patients with severe hypoxemia remains to be assessed. The aim of this study was to assess the incidence of low ScvO 2 in a cohort of hypoxemic patients and the association of this finding with differences in clinical management and patient outcomes. Methods: Retrospective review of data from adult intensive care unit patients with hypoxemia who required invasive mechanical ventilation for over 24 h and had at least one ScvO 2 measured within 6 h of a PaO 2 /FiO 2 ratio <200.

The Diagnostic Accuracy of Metagenomic Next-Generation Sequencing in Diagnosing Pneumonia: A Systemic Review and Meta-analysis.

Background: pneumonia (PCP) is a growing concern as the immunocompromised population expands. Current laboratory approaches are limited. This systematic review aimed to evaluate metagenomic next-generation sequencing (MNGS) tests' performance in detecting PCP.

Label-Free Optical Sensing and Medical Grade Resins: An Advanced Approach to Investigate Cell-Material Interaction and Biocompatibility.

The Corning Epic label-free (ELF) system is an innovative technology widely used in drug discovery, immunotherapy, G-protein-associated studies, and biocompatibility tests. Here, we challenge the use of ELF to further investigate the biocompatibility of resins used in manufacturing of blood filters, a category of medical devices representing life-saving therapies for the increasing number of patients with kidney failure. The biocompatibility assays were carried out by developing a cell model aimed at mimicking the clinical use of the blood filters and complementing the existing cytotoxicity assay requested by ISO10993-5.

Novel bioprinted 3D model to human fibrosis investigation.

Fibrosis is shared in multiple diseases with progressive tissue stiffening, organ failure and limited therapeutic options. This unmet need is also due to the lack of adequate pre-clinical models to mimic fibrosis and to be challenged novel by anti-fibrotic therapeutic venues. Here using bioprinting, we designed a novel 3D model where normal human healthy fibroblasts have been encapsulated in type I collagen.

Driver Drowsiness Detection: A Machine Learning Approach on Skin Conductance.

The majority of car accidents worldwide are caused by drowsy drivers. Therefore, it is important to be able to detect when a driver is starting to feel drowsy in order to warn them before a serious accident occurs. Sometimes, drivers are not aware of their own drowsiness, but changes in their body signals can indicate that they are getting tired.

Implementation of a Multimodal Knowledge-Exchange Platform to Provide Trauma Critical Care Education During the Ongoing Conflict in Ukraine.

Importance: The conflict in Ukraine has forced civilian hospitals with limited trauma and battlefield medicine experience to care for casualties of war, placing significant strain on the health care system. Using the Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN) program, a multimodal trauma critical care knowledge-exchange platform was created for clinicians practicing in these institutions.

Objectives: To describe the development and implementation of the CERTAIN for Ukraine program and to evaluate the reach of this intervention, together with participant engagement and satisfaction.

A transimpedance preamplifier using a feedforward approach for robust rejection of DC photogenerated currents.

The preamplifier proposed in this paper is designed to extract weak variable photogenerated signals from a high-level continuous background ensuring low noise and high transimpedance gain. An efficient cancellation of the DC component directly at the photodetector output, exploiting a feedforward approach, allows us to properly amplify the variable signal components of interest avoiding saturation of the preamplifier. Furthermore, the large transimpedance gain allows for minimizing the effects of the noise introduced by the following stages on the signal processing chain.

Vision-Based Eye Image Classification for Ophthalmic Measurement Systems.

The accuracy and the overall performances of ophthalmic instrumentation, where specific analysis of eye images is involved, can be negatively influenced by invalid or incorrect frames acquired during everyday measurements of unaware or non-collaborative human patients and non-technical operators. Therefore, in this paper, we investigate and compare the adoption of several vision-based classification algorithms belonging to different fields, i.e.

A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19.

The COVID-19 pandemic and the need for additional safe, effective, and affordable vaccines gave new impetus into development of vaccine genetic platforms. Here we report the findings from the phase 1, first-in-human, dose-escalation study of COVID-eVax, a DNA vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Sixty-eight healthy adults received two doses of 0.

Modulation of NMDA receptor activity by CR4056, an imidazoline-2 receptor ligand with analgesic properties.

CR4056 is an imidazoline-2 receptor ligand having potent analgesic activity and synergistic effect with opioids. Very recently it has been found that CR4056 can revert the cognitive impairment in animal models of Alzheimer's disease (AD). Since several lines of evidence highlight the importance of NMDAR modulators in nociceptive signaling and in AD progression, we considered as important to investigate the effects of CR4056 on NMDAR activity.

An IoT Measurement System Based on LoRaWAN for Additive Manufacturing.

The Industrial Internet of Things (IIoT) paradigm represents a significant leap forward for sensor networks, potentially enabling wide-area and innovative measurement systems. In this scenario, smart sensors might be equipped with novel low-power and long range communication technologies to realize a so-called low-power wide-area network (LPWAN). One of the most popular representative cases is the LoRaWAN (Long Range WAN) network, where nodes are based on the widespread LoRa physical layer, generally optimized to minimize energy consumption, while guaranteeing long-range coverage and low-cost deployment.

I2-Imidazoline Ligand CR4056 Improves Memory, Increases ApoE Expression and Reduces BBB Leakage in 5xFAD Mice.

Recent evidence suggests that I2-imidazoline ligands have neuroprotective properties in animal models of neurodegeneration, such as Alzheimer's disease (AD). We recently demonstrated that the I2-ligand BU224 reversed memory impairments in AD transgenic mice and this effect was not because of reductions in amyloid-β (Aβ) deposition. In this study, our aim was to determine the therapeutic potential of the powerful analgesic I2-imidazoline ligand CR4056 in the 5xFAD model of AD, since this ligand has been proven to be safely tolerated in humans.

A Comprehensive Review on Time Sensitive Networks with a Special Focus on Its Applicability to Industrial Smart and Distributed Measurement Systems.

The groundbreaking transformations triggered by the Industry 4.0 paradigm have dramatically reshaped the requirements for control and communication systems within the factory systems of the future. The aforementioned technological revolution strongly affects industrial smart and distributed measurement systems as well, pointing to ever more integrated and intelligent equipment devoted to derive accurate measurements.

Impact of the COVID-19 Pandemic on Urologic Oncology Surgery: Implications for Moving Forward.

The COVID-19 pandemic has caused the destruction of routine hospital services globally, leading to an increase in the backlog of elective surgery cases. The aim of the study was to retrospectively investigate the pandemic's impact on the urologic oncology surgical activity of a high-volume center located in Milan, Italy. The number and type of procedures performed in 2020 during the COVID-19 pandemic was evaluated using 2019 data as control.

COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models.

The COVID-19 pandemic caused by SARS-CoV-2 has made the development of safe and effective vaccines a critical priority. To date, four vaccines have been approved by European and American authorities for preventing COVID-19, but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle.