The potential of high temporal resolution automatic measurements of PM composition as an alternative to the filter-based manual method used in routine monitoring.

Under the EU Air Quality Directive (AQD) 2008/50/EC member states are required to undertake routine monitoring of PM composition at background stations. The AQD states for PM speciation this should include at least: nitrate , sulfate , chloride (Cl), ammonium (NH4), sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), elemental carbon (EC) and organic carbon (OC). Until 2017, it was the responsibility of each country to determine the methodology used to report the composition for the inorganic components of PM.

Achieving Inclusive Healthcare through Integrating Education and Research with AI and Personalized Curricula.

Precision medicine promises significant health benefits but faces challenges such as the need for complex data management and analytics, interdisciplinary collaboration, and education of researchers, healthcare professionals, and participants. Addressing these needs requires the integration of computational experts, engineers, designers, and healthcare professionals to develop user-friendly systems and shared terminologies. The widespread adoption of large language models (LLMs) like GPT-4 and Claude 3 highlights the importance of making complex data accessible to non-specialists.

Single-sample image-fusion upsampling of fluorescence lifetime images.

Fluorescence lifetime imaging microscopy (FLIM) provides detailed information about molecular interactions and biological processes. A major bottleneck for FLIM is image resolution at high acquisition speeds due to the engineering and signal-processing limitations of time-resolved imaging technology. Here, we present single-sample image-fusion upsampling, a data-fusion approach to computational FLIM super-resolution that combines measurements from a low-resolution time-resolved detector (that measures photon arrival time) and a high-resolution camera (that measures intensity only).

Inhibition of ATR opposes glioblastoma invasion through disruption of cytoskeletal networks and integrin internalization via macropinocytosis.

Background: Glioblastomas have highly infiltrative growth patterns that contribute to recurrence and poor survival. Despite infiltration being a critical therapeutic target, no clinically useful therapies exist that counter glioblastoma invasion. Here, we report that inhibition of ataxia telangiectasia and Rad 3 related kinase (ATR) reduces invasion of glioblastoma cells through dysregulation of cytoskeletal networks and subsequent integrin trafficking.

Correction: In situ 3D spatiotemporal measurement of soluble biomarkers in spheroid culture.

[This corrects the article DOI: 10.1007/s44164-022-00037-6.].

eIF4A1-dependent mRNAs employ purine-rich 5'UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation.

Altered eIF4A1 activity promotes translation of highly structured, eIF4A1-dependent oncogene mRNAs at root of oncogenic translational programmes. It remains unclear how these mRNAs recruit and activate eIF4A1 unwinding specifically to facilitate their preferential translation. Here, we show that single-stranded RNA sequence motifs specifically activate eIF4A1 unwinding allowing local RNA structural rearrangement and translation of eIF4A1-dependent mRNAs in cells.

Systematic review and meta-analysis of prevalence, trajectories, and clinical outcomes for frailty in COPD.

This systematic review synthesised measurement and prevalence of frailty in COPD and associations between frailty and adverse health outcomes. We searched Medline, Embase and Web of Science (1 January 2001-8 September 2021) for observational studies in adults with COPD assessing frailty prevalence, trajectories, or association with health-related outcomes. We performed narrative synthesis and random-effects meta-analyses.

In situ 3D spatiotemporal measurement of soluble biomarkers in spheroid culture.

Background: Advanced cell culture techniques such as 3D bioprinting and hydrogel-based cell embedding techniques harbor many new and exciting opportunities to study cells in environments that closely recapitulate in vivo conditions. Researchers often study these environments using fluorescence microscopy to visualize the protein association with objects such as cells within the 3D environment, yet quantification of concentration profiles in the microenvironment has remained elusive.

Objective: Demonstrate an assay that enables near real-time in situ biomarker detection and spatiotemporal quantification of biomarker concentration in 3D cell culture.

Analysis of Prostate Cancer Tumor Microenvironment Identifies Reduced Stromal CD4 Effector T-cell Infiltration in Tumors with Pelvic Nodal Metastasis.

Background: Pelvic nodal metastasis in prostate cancer impacts patient outcome negatively.

Objective: To explore tumor-infiltrating immune cells as a potential predictive tool for regional lymph node (LN) metastasis.

Design Setting And Participants: We applied multiplex immunofluorescence and targeted transcriptomic analysis on 94 radical prostatectomy specimens in patients with (LN+) or without (LN-) pelvic nodal metastases.

Exposure to Microbial Metabolite Butyrate Prolongs the Survival Time and Changes the Growth Pattern of Human Papillomavirus 16 E6/E7-Immortalized Keratinocytes in Vivo.

Human papillomavirus (HPV) is a ubiquitous human pathogen that can be cleared by host immunity. Nonetheless, a small percentage of the patients develop persistent infection with oncogenic HPV, which poses an increased risk of developing HPV-associated malignancy. Although cell-mediated immunity is a known systemic factor, local factors that influence persistent HPV infection have not been fully investigated.

A RAC-GEF network critical for early intestinal tumourigenesis.

RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets.

A risk-stratified approach toward safely resuming OnabotulinumtoxinA injections based on dosing and ambulatory status in pediatric patients with cerebral palsy during the Coronavirus pandemic of 2019 (COVID-19).

Purpose: After the onset of the Coronavirus pandemic of 2019-2020 (COVID-19), physicians who inject OnabotulinumtoxinA (BoNT-A) were left with determining risks and benefits in pediatric patients with cerebral palsy. Many of these patients have pre-existing conditions that make them more prone to COVID-19 symptoms, and this susceptibility potentially increases after BoNT-A injections.

Methods: A retrospective chart review of 500 patients identified 256 pediatric patients with cerebral palsy who received an intramuscular BoNT-A injection to determine relative doses used for each Gross Motor Functional Classification Score (GMFCS).

The RAC1 Target NCKAP1 Plays a Crucial Role in the Progression of Braf;Pten-Driven Melanoma in Mice.

BRAF is the most common driver mutation in human cutaneous melanoma and is frequently accompanied by loss of the tumor-suppressing phosphatase PTEN. Recent evidence suggests a co-operative role for RAC1 activity in BRAF-driven melanoma progression and drug resistance. However, the underlying molecular mechanisms and the role of RAC1 downstream targets are not well-explored.

Variability of Steady State Oral Baclofen Prescribing Practices in Pediatric Patients With Cerebral Palsy.

The aim of the study was to identify oral baclofen dosing variability at steady state based on weight and Gross Motor Function Classification System level using a retrospective cross-sectional study design. The medical records of 500 pediatric aged patients (age 1-21 yrs) were reviewed to obtain 144 pediatric patients who met inclusion criteria. One-way analysis of variance tests revealed increasing mean doses in baclofen (in milligram per kilogram) with higher Gross Motor Function Classification System levels (P = 0.

N-WASP Control of LPAR1 Trafficking Establishes Response to Self-Generated LPA Gradients to Promote Pancreatic Cancer Cell Metastasis.

Pancreatic ductal adenocarcinoma is one of the most invasive and metastatic cancers and has a dismal 5-year survival rate. We show that N-WASP drives pancreatic cancer metastasis, with roles in both chemotaxis and matrix remodeling. lysophosphatidic acid, a signaling lipid abundant in blood and ascites fluid, is both a mitogen and chemoattractant for cancer cells.

Hydration Control of Gel-Adhesion and Muco-Adhesion.

Protective mucin gel layers established by epithelial cell surfaces in biology have water contents above 90% and provide a low-shear stress nonadhesive interfacial boundary on epithelial surfaces throughout the body. Adhesion between gels and mucin layers, muco-adhesion, is an important aspect of drug delivery, biocompatibility, and the prevention of damage during insertion, use, and removal of medical devices in contact with moist epithelial surfaces. This manuscript develops a simple mathematical model to suggest that gel-adhesion and muco-adhesion are controlled by dehydration.

Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans.

Group 2 innate lymphoid cells (ILC2s) are enriched in mucosal tissues (e.g., lung) and respond to epithelial cell-derived cytokines initiating type 2 inflammation.

Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels.

Mutant p53s (mutp53) increase cancer invasiveness by upregulating Rab-coupling protein (RCP) and diacylglycerol kinase-α (DGKα)-dependent endosomal recycling. Here we report that mutp53-expressing tumour cells produce exosomes that mediate intercellular transfer of mutp53's invasive/migratory gain-of-function by increasing RCP-dependent integrin recycling in other tumour cells. This process depends on mutp53's ability to control production of the sialomucin, podocalyxin, and activity of the Rab35 GTPase which interacts with podocalyxin to influence its sorting to exosomes.

CSF1R Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapies including single-agent immunotherapy and has a dense desmoplastic stroma, and most patients present with advanced metastatic disease. We reveal that macrophages are the dominant leukocyte population both in human PDAC stroma and autochthonous models, with an important functional contribution to the squamous subtype of human PDAC. We targeted macrophages in a genetic PDAC model using AZD7507, a potent selective inhibitor of CSF1R.

A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts.

The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET) biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo.

Elimination of Cancer Health Disparities through the Acceleration of HPV Vaccines and Vaccinations: A Simplified Version of the President's Cancer Panel Report on HPV Vaccinations.

The human papillomavirus (HPV) is a major public health concern affecting both females and males. HPV is associated with cervical, anal, head and neck cancers. About 99% of all cervical cancers are related to HPV.