Biomarkers of Parkinson's Disease.

Background: Parkinson's disease (PD) is a degenerative brain disease characterised by motor and non-motor symptoms. Motor disabilities, including dystonia and dyskinesia, cause speech and movement difficulties and limit many aspects of life. Factors affecting PD refer to the various internal and external conditions that contribute to the onset, severity and progression of the disease.

BH3 Mimetics Augment Cytotoxic T Cell Killing of Acute Myeloid Leukemia via Mitochondrial Apoptotic Mechanism.

Adoptive cell therapy (ACT) can address an unmet clinical need for patients with relapsed/refractory acute myeloid leukemia (AML), but its effect is often modest in the setting of high tumor burden. In this study, we postulated that strategies to lower the AML apoptotic threshold will augment T cell killing of AML cells. BH3 mimetics, such as venetoclax, are a clinically approved class of compounds that predispose cells to intrinsic apoptosis by inhibiting anti-apoptotic mitochondrial proteins.

Trends in adolescent and adult vaccination in pharmacy and medical settings in the United States, 2018-2024: a database study.

Background: Pharmacies can increase access to vaccines. This study aimed to describe trends in the proportion of adolescent and adult vaccinations administered in pharmacies in the United States from 2018 to 2024.

Research Design And Methods: This was a retrospective cross-sectional analysis of medical and pharmacy claims from commercial health insurance enrollees.

Navigating regulatory and policy challenges for AI enabled combination devices.

In recent years, the Artificial Intelligence (AI) has enabled conventional Combination Devices (CDs) to innovate in healthcare merging with technology sectors. However, the challenges like reliance on predicate devices in US Food and Drug Administration (FDA's 510(k) pathway, especially for perpetually updating AI are stressed. Though the European Union (EU's new Medical Device Regulations address software and AI, fitting adaptive algorithms into conformity assessments remains difficult.

Recovery from HPV vaccination deficits caused by the COVID-19 pandemic in Germany: a modeling study of catch-up HPV vaccination among adolescent girls.

Health care disruptions associated with the COVID-19 pandemic have caused persistent decreases in human papillomavirus (HPV) vaccination uptake in Germany. The objective of this study was to estimate the cumulative deficit in first doses of the HPV vaccine administered to girls in Germany since the beginning of the pandemic and the projected time to recover from this deficit at different catch-up vaccination uptake levels, focusing on girls 9-14 years of age. This study used a published HPV vaccination modeling tool.

Critical assessment of LC3/GABARAP ligands used for degrader development and ligandability of LC3/GABARAP binding pockets.

Recent successes in developing small molecule degraders that act through the ubiquitin system have spurred efforts to extend this technology to other mechanisms, including the autophagosomal-lysosomal pathway. Therefore, reports of autophagosome tethering compounds (ATTECs) have received considerable attention from the drug development community. ATTECs are based on the recruitment of targets to LC3/GABARAP, a family of ubiquitin-like proteins that presumably bind to the autophagosome membrane and tether cargo-loaded autophagy receptors into the autophagosome.

Modeling the health and economic implications of adopting a 1-dose 9-valent human papillomavirus vaccination program in adolescents in low/middle-income countries: An analysis of Indonesia.

Background: Recent evidence suggests that 1 dose of the human papillomavirus (HPV) vaccine may have similar effectiveness in reducing HPV infection risk compared to 2 or 3 doses.

Objective: To evaluate the public health impact and cost-effectiveness of implementing a 1-dose or a 2-dose program of the 9-valent HPV vaccine in a low- and middle-income country (LMIC).

Methods: We adapted a dynamic transmission model to the Indonesia setting, and conducted a probabilistic sensitivity analysis using distributions reflecting the uncertainty in levels and durability of protection of a 1-dose that were estimated under a Bayesian framework incorporating 3-year vaccine efficacy data from the KEN SHE trial (base-case) and 10 year effectiveness data from the India IARC study (alternative analysis).

Understanding the Effectiveness of Cognitive Behavioural Therapy: A Study on Offenders.

Background: Cognitive behavioural therapy (CBT) is well known for its effectiveness in addressing psychiatric disorders such as depression, anxiety, PTSD, and borderline personality disorder, often used alongside medication.

Summary: CBT is used more often in the criminal justice system to help rehabilitate offenders by targeting cognitive distortions affecting their social and decision-making abilities. These maladaptive behaviours and sense of entitlement can result from distortions, which CBT works to address by restructuring thought patterns and encouraging adaptive behaviours.

Pilot Randomized Clinical Trial of a Passive Non-invasive Positive End-Expiratory Pressure (PEEP) Device for Delivering Positive Pressure Therapy Compared to Standard Care in Non-critically Ill Patients With COVID-19.

Background: During the COVID-19 pandemic, there were reports of a shortage of ventilators and oxygen supply, particularly in resource-limited settings. We report the preliminary evaluation of a non-invasive positive end-expiratory pressure (PEEP) mask in hospitalized non-critically ill patients with COVID-19.

Methods: We randomly assigned hospitalized adult patients with confirmed COVID-19 infection and requiring greater than 40% supplemental oxygen to either standard care oxygen delivery (control) or via Materialise passive non-invasive PEEP device mask (intervention; Belgium).

Parent perceptions of various treatment approaches for PANS and PANDAS.

Pediatric autoimmune neuropsychiatric disorder (PANDAS) is characterized by sudden, dramatic onset obsessive-compulsive disorder (OCD) following a Group A Streptococcus infection. Pediatric acute neuropsychiatric syndrome (PANS) refers to sudden, dramatic onset OCD and/or restricted eating triggered by infections and other inflammatory reactions. A variety of treatments have been utilized for PANS/PANDAS; however, there is no "gold standard" intervention protocol.

Investors reward countries for participating in climate agreements.

International climate agreements are one of the best-known approaches to coordinating climate actions among governments but face a free-rider problem, where individual governments lack sufficient incentives to reduce emissions. This study examines the role of investors in providing rewards to governments through sovereign bond yields to encourage climate cooperation and reduce emission intensity. Using a difference-in-differences method, this study examines how sovereign bond yields change around the Kyoto Protocol and the Paris Agreement.

Brain-wide neural recordings in mice navigating physical spaces enabled by robotic neural recording headstages.

Technologies that can record neural activity at cellular resolution at multiple spatial and temporal scales are typically much larger than the animals that are being recorded from and are thus limited to recording from head-fixed subjects. Here we have engineered robotic neural recording devices-'cranial exoskeletons'-that assist mice in maneuvering recording headstages that are orders of magnitude larger and heavier than the mice, while they navigate physical behavioral environments. We discovered optimal controller parameters that enable mice to locomote at physiologically realistic velocities while maintaining natural walking gaits.

Pain Perception, Knowledge, Attitude, and Diet Diversity in Patients Undergoing Fixed Orthodontic Treatment: A Pilot Study.

Objective: This study aimed to determine the correlation between pain perception and knowledge, attitude, and diet diversity in patients undergoing fixed orthodontic treatment.

Methods: A total of 103 patients (15-40 yrs.; 67 females, 36 males) undergoing orthodontic treatment with a 0.

Computer vision-guided open-source active commutator for neural imaging in freely behaving animals.

Significance: Recently developed miniaturized neural recording devices that can monitor and perturb neural activity in freely behaving animals have significantly expanded our knowledge of neural underpinning of complex behaviors. Most miniaturized neural interfaces require a wired connection for external power and data acquisition systems. The wires are required to be commutated through a slip ring to accommodate for twisting of the wire or tether and alleviate torsional stresses.

Auriferous nanozymes: advances in diagnostic and therapeutic applications.

Nanozymes are a group of nanomaterials that garnered significant attention due to their enzyme-mimicking properties and their catalytic activities comparable to those of natural enzymes. The ability of nanozymes to emulate crucial biological processes which can conquer the drawbacks of natural enzymes, such as their restricted thermostability as well as substrate range. Auriferous (gold) nanozymes possess remarkable enzyme-like properties, such as reductase, peroxidase, superoxide dismutase, oxidase, and catalase.

Glutaminase inhibition in combination with azacytidine in myelodysplastic syndromes: a phase 1b/2 clinical trial and correlative analyses.

Malignancies are reliant on glutamine as an energy source and a facilitator of aberrant DNA methylation. We demonstrate preclinical synergy of telaglenastat (CB-839), a selective glutaminase inhibitor, combined with azacytidine (AZA), followed by a single-arm, open-label, phase 1b/2 study in persons with advanced myelodysplastic syndrome (MDS). The dual primary endpoints evaluated clinical activity, safety and tolerability; secondary endpoints evaluated pharmacokinetics, pharmacodynamics, overall survival, event-free survival and duration of response.

Development and validation of 3D printed anthropomorphic head phantom with eccentric holes for medical LINAC quality assurance testing in stereotactic radiosurgery.

Stereotactic Radiosurgery (SRS) for brain tumors using Medical Linear Accelerator (LINAC) demands high precision and accuracy. A specific Quality Assurance (QA) is essential for every patient undergoing SRS to protect nearby non-cancerous cells by ensuring that the X-ray beams are targeted according to tumor position. In this work, a water-filled generic anthropomorphic head phantom consisting of two removable parts with eccentric holes was developed using Additive Manufacturing (AM) process for performing QA in SRS.

Phosphorus recovery potential from sewage sludge by struvite precipitation: remodelling policy framework in Rajasthan, India.

The manufacturing of fossil-based fertilizers by extraction of rock phosphate has contributed to carbon emissions and depleted the non-renewable phosphorus reserves. Sewage sludge, which is a waste product from Sewage Treatment Plants (STPs), is rich in phosphorus. The existing techniques for sludge management contribute to carbon emissions and ecological footprint.

Surface enhanced raman spectroscopy based sensitive and onsite detection of microplastics in water utilizing silver nanoparticles and nanodendrites.

Plastics, of the order of microns in size, being not visible to the naked eye, are one of the significant contributors to pollution in the environment. Thus, the detection of micron-sized plastics (microplastics (MPs)) is crucial because of its hazardous toxic effects on our surroundings. In this work, we have proposed a quick and on-site detection of MPs, such as, polyvinyl chloride (PVC), polyvinyl alcohol (PVA) and polystyrene (PS) at ultra trace level using surface-enhanced Raman spectroscopy (SERS).

Designing Nanocomposite-Based Electrochemical Biosensors for Diabetes Mellitus Detection: A Review.

This review will unveil the development of a new generation of electrochemical sensors utilizing a transition-metal-oxide-based nanocomposite with varying morphology. There has been considerable discussion on the role of transition metal oxide-based nanocomposite, including iron, nickel, copper, cobalt, zinc, platinum, manganese, conducting polymers, and their composites, in electrochemical and biosensing applications. Utilizing these materials to detect glucose and hydrogen peroxide selectively and sensitively with the correct chemical functionalization is possible.

Back-Pocket Optimization of 2-Aminopyrimidine-Based Macrocycles Leads to Potent EPHA2/GAK Kinase Inhibitors.

Macrocyclization of acyclic compounds is a powerful strategy for improving inhibitor potency and selectivity. Here we have optimized 2-aminopyrimidine-based macrocycles to use these compounds as chemical tools for the ephrin kinase family. Starting with a promiscuous macrocyclic inhibitor, , we performed a structure-guided activity relationship and selectivity study using a panel of over 100 kinases.

Cimicifugin, a broad-spectrum inhibitor of and CDK7.

Cyclin-dependent kinase 7 is an attractive therapeutic target for the treatment of cancers, and a previous report suggested that CDK7 is a potential drug target for developing new anti-malarial drugs. In this study, we aimed to characterize and evaluate the drug target potential of CDK7. is responsible for tropical theileriosis, which induces a phenotype similar to cancerous cells like immortalization, hyperproliferation, and dissemination.