Targeted delivery of DAPT using dual antibody functionalized solid lipid nanoparticles for enhanced anti-tumour activity against triple negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype known for its aggressive nature, high rates of recurrence, and treatment resistance, largely attributed to the presence of breast cancer stem cells (BCSCs). Traditional therapies often struggle to eliminate BCSCs, which contributes to tumor recurrence. One promising strategy for addressing this challenge is targeting the Notch signaling pathway, which plays a critical role in the self-renewal and maintenance of BCSCs.

Novel multimodal sensing and machine learning strategies to classify cognitive workload in laparoscopic surgery.

Background: Surgeons can experience elevated cognitive workload (CWL) during surgery due to various factors including operative technicalities and the environmental demands of the operating theatre. This can result in poorer outcomes and have a detrimental effect on surgeon well-being. The objective measurement of CWL provides a potential solution to facilitate classification of workload levels, however results are variable when physiological measures are used in isolation.

A radioligand for in vitro autoradiography of CSF1R in post-mortem CNS tissues.

Background: Reactive microglia and recruited peripheral macrophages contribute to the pathogenesis of Alzheimer's dementia (AD). Monocytes, macrophages and microglia all express the marker colony-stimulating factor 1 receptor (CSF1R). 4-Cyano-N-(4-(4-methylpiperazin-1-yl)-2-(4-methylpiperidin-1-yl)phenyl)-1H-pyrrole-2-carboxamide (1) is a high-affinity antagonist for CSF1R.

Development and validation of a virtual teaching method for minimally invasive surgery skills: a prospective cohort study.

Introduction: The COVID-19 pandemic led to a significant reduction in operative exposure for surgical trainees, necessitating alternative training methods to mitigate the impact on surgical education. This study sought to evaluate whether minimally invasive surgery (MIS) skills could be taught remotely using widely available technology with objective assessments of proficiency.

Methods: This was a pilot observational study with a comparative assessment of face-to-face (F2F) and virtual training of novice learners in MIS skills.

Objective Assessment of Cognitive Workload in Surgery: A Systematic Review.

Objective: To systematically review technologies that objectively measure CWL in surgery, assessing their psychometric and methodological characteristics.

Summary Background Data: Surgical tasks involving concurrent clinical decision-making and the safe application of technical and non-technical skills require a substantial cognitive demand and resource utilization. Cognitive overload leads to impaired clinical decision-making and performance decline.

Stimulated Emission of Signal Photons from Dark Matter Waves.

The manipulation of quantum states of light has resulted in significant advancements in both dark matter searches and gravitational wave detectors. Current dark matter searches operating in the microwave frequency range use nearly quantum-limited amplifiers. Future high frequency searches will use photon counting techniques to evade the standard quantum limit.

The impact of collaborative organisational models and general practice size on patient safety and quality of care in the English National Health Service: A systematic review.

Collaborative primary care has become an increasingly popular strategy to manage existing pressures on general practice. In England, the recent changes taking place in the primary care sector have included the formation of collaborative organisational models and a steady increase in practice size. The aim of this review was to summarise the available evidence on the impact of collaborative models and general practice size on patient safety and quality of care in England.

High-fidelity qutrit entangling gates for superconducting circuits.

Ternary quantum information processing in superconducting devices poses a promising alternative to its more popular binary counterpart through larger, more connected computational spaces and proposed advantages in quantum simulation and error correction. Although generally operated as qubits, transmons have readily addressable higher levels, making them natural candidates for operation as quantum three-level systems (qutrits). Recent works in transmon devices have realized high fidelity single qutrit operation.

The Measurement of Cognitive Workload in Surgery Using Pupil Metrics: A Systematic Review and Narrative Analysis.

Introduction: Increased cognitive workload (CWL) is a well-established entity that can impair surgical performance and increase the likelihood of surgical error. The use of pupil and gaze tracking data is increasingly being used to measure CWL objectively in surgery. The aim of this review is to summarize and synthesize the existing evidence that surrounds this.

PET/CT imaging of CSF1R in a mouse model of tuberculosis.

Purpose: Macrophages represent an essential means of sequestration and immune evasion for Mycobacterium tuberculosis. Pulmonary tuberculosis (TB) is characterized by dense collections of tissue-specific and recruited macrophages, both of which abundantly express CSF1R on their outer surface. 4-Cyano-N-(5-(1-(dimethylglycyl)piperidin-4-yl)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-2-yl)-1H-imidazole-2-carboxamide (JNJ-28312141) is a reported high affinity, CSF1R-selective antagonist.

SARS-CoV-2 neutralizing capacity among blood donors without prior COVID-19 symptomatic history vs. blood donors with prior COVID-19 symptomatic history: A comparative study.

Introduction: Though moderate to severely ill COVID-19 patients are being treated using COVID Convalescent plasma across the world, there is a lack of standardization or information about the relative neutralizing capacity of antibodies from convalescent plasma donors. The current study aimed to compare the neutralizing antibody inhibition levels between COVID-Convalescent plasma from apheresis donors who had symptomatic COVID-19 history and asymptomatic blood donors, i.e.

Hardware-Efficient Microwave-Activated Tunable Coupling between Superconducting Qubits.

Generating high-fidelity, tunable entanglement between qubits is crucial for realizing gate-based quantum computation. In superconducting circuits, tunable interactions are often implemented using flux-tunable qubits or coupling elements, adding control complexity and noise sources. Here, we realize a tunable ZZ interaction between two transmon qubits with fixed frequencies and fixed coupling, induced by driving both transmons off resonantly.

Seamless High-Q Microwave Cavities for Multimode Circuit Quantum Electrodynamics.

Multimode cavity quantum electrodynamics-where a two-level system interacts simultaneously with many cavity modes-provides a versatile framework for quantum information processing and quantum optics. Because of the combination of long coherence times and large interaction strengths, one of the leading experimental platforms for cavity QED involves coupling a superconducting circuit to a 3D microwave cavity. In this work, we realize a 3D multimode circuit QED system with single photon lifetimes of 2 ms across 9 modes of a novel seamless cavity.

Dual Inhibition of P-gp and BCRP Improves Oral Topotecan Bioavailability in Rodents.

P-glycoprotein (P-gp) inhibition has been studied to overcome multidrug resistance in cancer chemotherapy but failed in clinical trials due to low/toxic effects. Recently, a dual modulation of transporters and natural derivatives have been examined to surmount this limitation. We examined breast cancer resistance protein (BCRP) inhibition in vitro and in vivo by P-gp inhibitors derived from natural compounds in previous studies.

Searching for Dark Matter with a Superconducting Qubit.

Detection mechanisms for low mass bosonic dark matter candidates, such as the axion or hidden photon, leverage potential interactions with electromagnetic fields, whereby the dark matter (of unknown mass) on rare occasion converts into a single photon. Current dark matter searches operating at microwave frequencies use a resonant cavity to coherently accumulate the field sourced by the dark matter and a near standard quantum limited (SQL) linear amplifier to read out the cavity signal. To further increase sensitivity to the dark matter signal, sub-SQL detection techniques are required.

The disubstituted adamantyl derivative LW1564 inhibits the growth of cancer cells by targeting mitochondrial respiration and reducing hypoxia-inducible factor (HIF)-1α accumulation.

Targeting cancer metabolism has emerged as an important cancer therapeutic strategy. Here, we describe the synthesis and biological evaluation of a novel class of hypoxia-inducible factor (HIF)-1α inhibitors, disubstituted adamantyl derivatives. One such compound, LW1564, significantly suppressed HIF-1α accumulation and inhibited the growth of various cancer cell lines, including HepG2, A549, and HCT116.

Radiosynthesis and validation of [5-cyano-N-(4-(4-[ C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl) furan-2-carboxamide] ([ C]CPPC), a PET radiotracer for imaging CSF1R, a microglia-specific marker.

In this practitioner protocol, the radiochemical synthesis of [ C]CPPC is described in detail, and a quality control summary of three validation productions is presented. The results indicate that the radiotracer product can be produced in good radiochemical yield (> 60 mCi (2.22 GBq) at end-of-synthesis (EOS)), at high specific activity (molar activity > 11,435 mCi/μmole (423 GBq/μmole) at EOS) and high chemical and radiochemical purity.

Mechanism of the natural product moracin-O derived MO-460 and its targeting protein hnRNPA2B1 on HIF-1α inhibition.

Hypoxia-inducible factor-1α (HIF-1α) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of HIF-1α in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear.

PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R).

While neuroinflammation is an evolving concept and the cells involved and their functions are being defined, microglia are understood to be a key cellular mediator of brain injury and repair. The ability to measure microglial activity specifically and noninvasively would be a boon to the study of neuroinflammation, which is involved in a wide variety of neuropsychiatric disorders including traumatic brain injury, demyelinating disease, Alzheimer's disease (AD), and Parkinson's disease, among others. We have developed [C]CPPC [5-cyano--(4-(4-[C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide], a positron-emitting, high-affinity ligand that is specific for the macrophage colony-stimulating factor 1 receptor (CSF1R), the expression of which is essentially restricted to microglia within brain.

Synthesis and Evaluation of a New F-Labeled Radiotracer for Studying the GABA Receptor in the Mouse Brain.

New GABA agonists, fluoropyridyl ether analogues of baclofen, have been synthesized as potential PET radiotracers. The compound with highest inhibition binding affinity as well as greatest agonist response, ( R)-4-amino-3-(4-chloro-3-((2-fluoropyridin-4-yl)methoxy)phenyl)butanoic acid (1b), was radiolabeled with F with good radiochemical yield, high radiochemical purity, and high molar radioactivity. The regional brain distribution of the radiolabeled ( R)-4-amino-3-(4-chloro-3-((2-[F]fluoropyridin-4-yl)methoxy)phenyl)butanoic acid, [F]1b, was studied in CD-1 male mice.

Efficacy of Denture Cleansers on Impact Strength of Heat polymerized Acrylic Resins.

Purpose: The study was aimed to compare and evaluate the changes in the impact strength of heat cure denture base resins when treated using denture cleansers.

Methodology: Study was conducted with sample size of 40 and dimesion 65 mm length, 10 mm width, and 3 mm thickness as per the ISO 1567. Distilled water has been used as control group, in which 10 samples were immersed of 40 samples.

Comparative Evaluation of Tensile Strength in Die Stone Incorporated with Sodium and Calcium Hypochlorite as Disinfectants: An in vitro Study.

Aim: The aim of this study was to evaluate the tensile strength of die stone incorporated with sodium and calcium hypochlorite as disinfectants.

Materials And Methods: Two commercially available type IV die stone (Kalrock: Kalabhai Karson Pvt., Ltd and Pearlstone: Asian Chemicals) and two commercially available disinfectant solutions (sodium hypochlorite and calcium hypochlorite: Beachem Laboratory Chemical Private Limited, Chennai and Leo Chem Private Limited, Bengaluru) were used in this study, and the tensile strength was measured using Lloyd's Universal Testing Machine.

Methyl 3-(3-(4-(2,4,4-Trimethylpentan-2-yl)phenoxy)-propanamido)benzoate as a Novel and Dual Malate Dehydrogenase (MDH) 1/2 Inhibitor Targeting Cancer Metabolism.

Previously, we reported a hypoxia-inducible factor (HIF)-1 inhibitor LW6 containing an (aryloxyacetylamino)benzoic acid moiety inhibits malate dehydrogenase 2 (MDH2) using a chemical biology approach. Structure-activity relationship studies on a series of (aryloxyacetylamino)benzoic acids identified selective MDH1, MDH2, and dual inhibitors, which were used to study the relationship between MDH enzyme activity and HIF-1 inhibition. We hypothesized that dual inhibition of MDH1 and MDH2 might be a powerful approach to target cancer metabolism and selected methyl-3-(3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propanamido)-benzoate (16c) as the most potent dual inhibitor.

Isolated supravalvular aortic stenosis with left ventricular diverticulum and cleft mitral valve: Surgical repair in adulthood.

Supravalvular aortic stenosis is an uncommon but well characterized congenital narrowing of the ascending aorta above the level of the coronary arteries. It can be a familial disorder, can occur sporadically, or can be associated with Williams syndrome. We are reporting a very rare presentation of supravalvular aortic stenosis with associated left ventricular diverticulum and cleft mitral valve.