Metrics for studying the porous void space of packed particles.

Characterizing porosity in packed particle assemblies is a complex task that requires advanced analytical tools. We present a visually rich and extensive library of global, pore-based, and other metrics for analyzing features of porosity in such assemblies. Our library includes over 25 descriptors of "3D pores" that are identified using our LOVAMAP software.

Facile Automated Radiosynthesis of an Arginine Selective Bioconjugation Reagent 4‑[F]Fluorophenylglyoxal for Developing Protein-Based PET Molecular Probes.

4-[F]-Fluorophenylglyoxal ([F]-FPG) is a novel arginine selective bioconjugation reagent for native protein F-labeling. Here, we report the automated radiosynthesis of [F]-FPG on a Scintomics GRP module. The radiochemical preparation was performed in a one-pot, two-step process using a DMSO-resistant cassette system.

Discovery of liver-selective glucokinase activators comprising N-(4-alkylthiazol-2-yl)benzamides and N-(3-alkyl-1,2,4-thiadiazol-5-yl)benzamides for the treatment of metabolic disorders.

Glucokinase ("GK") plays a critical role in regulating glucose homeostasis within the body. Proof-of-concept animal models demonstrated that small molecule GK activation enhances glucose uptake and utilization by various tissues, including liver and pancreas. Accordingly, glucokinase activators ("GKAs") were extensively explored as a potential therapy for carbohydrate metabolism disorders.

Nebulized dexmedetomidine in the treatment of obstetric post-dural puncture headache: two case reports.

Post-dural puncture headache (PDPH) is a debilitating complication of neuraxial anesthesia, particularly prevalent in obstetric patients, usually characterized by a postural headache. PDPH is hypothesized to result from cerebrospinal fluid leakage through a dural puncture, triggering symptoms like neck stiffness and subjective hearing changes. While conservative measures are common for treatment, more refractory cases may require invasive interventions such as an epidural blood patch (EBP).

Novel [F]FPG-interleukin-2 conjugate for monitoring immune checkpoint therapy with positron emission tomography.

F-interleukin-2 based PET imaging of activated T cells serves as a potential tool for non-invasive response prediction, treatment evaluation, and patient stratification in cancer immune checkpoint therapy. Herein, we report the radiolabelling of interleukin-2 (IL-2) with a novel arginine selective bioconjugation reagent, 4-[F]fluorophenylglyoxal ([F]FPG). Good non-decay corrected bioconjugation efficiencies of 29 ± 4 % (n = 5) were obtained for the [F]FPG-IL-2.

Identification and analysis of 3D pores in packed particulate materials.

We took the classic 'guess the number of beans in a jar game' and amplified the research question. Rather than estimate the quantity of particles in the jar, we sought to characterize the spaces between them. Here we present an approach for delineating the pockets of empty space (three-dimensional pores) between packed particles, which are hotspots for activity in applications and natural phenomena that deal with particulate materials.

An immunoinformatics assessment of the cancer testis antigen, DDX53, as a potential early esophageal cancer antigen.

T-lymphocytes have been implicated in facilitating a pro-inflammatory, pro-tumorigenic microenvironment that worsens prognosis for esophageal carcinoma (ESCA). In this study, we identified tumor resident, T-cell receptor (TCR) complementarity determining region-3 (CDR3) amino acid sequences and employed an algorithm particularly suited to the big data setting to evaluate TCR CDR3-cancer testis antigen (CTA) chemical complementarities. Chemical complementarity of the ESCA TCR CDR3s and the cancer testis antigen DDX53 represented a disease-free survival (DFS) distinction, whereby the upper fiftieth percentile complementarity group correlated with worse DFS.

The feasibility of ideography as an empirical question for a science representational systems design.

The possibility of ideography is an empirical question. Prior examples of graphic codes do not provide compelling evidence for the infeasibility of ideography, because they fail to satisfy essential cognitive requirements that have only recently been revealed by studies of representational systems in cognitive science. Design criteria derived from cognitive principles suggest how effective graphic codes may be engineered.

Void Volume Fraction of Granular Scaffolds.

Void volume fraction (VVF) is a global measurement frequently used to characterize the void space of granular scaffolds, yet there is no gold standard by which to measure VVF in practice. To study the relationship  between VVF and particles of varying size, form, and composition, a library of 3D simulated scaffolds is used. Results reveal that relative to particle count, VVF is a less predictable metric across replicate scaffolds.

Imaging Memory T-Cells Stratifies Response to Adjuvant Metformin Combined with αPD-1 Therapy.

The low response rates associated with immune checkpoint inhibitor (ICI) use has led to a surge in research investigating adjuvant combination strategies in an attempt to enhance efficacy. Repurposing existing drugs as adjuvants accelerates the pace of cancer immune therapy research; however, many combinations exacerbate the immunogenic response elicited by ICIs and can lead to adverse immune-related events. Metformin, a widely used type 2 diabetes drug is an ideal candidate to repurpose as it has a good safety profile and studies suggest that metformin can modulate the tumour microenvironment, promoting a favourable environment for T cell activation but has no direct action on T cell activation on its own.

Imaging Effector Memory T-Cells Predicts Response to PD1-Chemotherapy Combinations in Colon Cancer.

Often, patients fail to respond to immune checkpoint inhibitor (ICI) treatment despite favourable biomarker status. Numerous chemotherapeutic agents have been shown to promote tumour immunogenicity when used in conjunction with ICIs; however, little is known about whether such combination therapies lead to a lasting immune response. Given the potential toxicity of ICI-chemotherapy combinations, identification of biomarkers that accurately predict how individuals respond to specific treatment combinations and whether these responses will be long lasting is of paramount importance.

Haploinsufficiency of CYP8B1 associates with increased insulin sensitivity in humans.

BACKGROUNDCytochrome P450 family 8 subfamily B member 1 (CYP8B1) generates 12α-hydroxylated bile acids (BAs) that are associated with insulin resistance in humans.METHODSTo determine whether reduced CYP8B1 activity improves insulin sensitivity, we sequenced CYP8B1 in individuals without diabetes and identified carriers of complete loss-of-function (CLOF) mutations utilizing functional assays.RESULTSMutation carriers had lower plasma 12α-hydroxylated/non-12α-hydroxylated BA and cholic acid (CA)/chenodeoxycholic acid (CDCA) ratios compared with age-, sex-, and BMI-matched controls.

Overcoming Limitations in Decarboxylative Arylation via Ag-Ni Electrocatalysis.

A useful protocol for achieving decarboxylative cross-coupling (DCC) of redox-active esters (RAE, isolated or generated in situ) and halo(hetero)arenes is reported. This pragmatically focused study employs a unique Ag-Ni electrocatalytic platform to overcome numerous limitations that have plagued this strategically powerful transformation. In its optimized form, coupling partners can be combined in a surprisingly simple way: open to the air, using technical-grade solvents, an inexpensive ligand and Ni source, and substoichiometric AgNO, proceeding at room temperature with a simple commercial potentiostat.

Measurement of Extraneous and Germane Cognitive Load in the Mathematics Addition Task: An Event-Related Potential Study.

Cognitive load significantly influences learning effectiveness. All the three types of cognitive load-intrinsic, extraneous, and germane-are important for guiding teachers in preparing effective instructional designs for students. However, the techniques used to assess the relationship between brain activity and cognitive load during learning activities require further investigation.

Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a notoriously difficult cancer to treat. The recent development of immune checkpoint inhibitors has revolutionised HCC therapy; however, successful response is only observed in a small percentage of patients. Biomarkers typically used to predict treatment response in other tumour types are ineffective in HCC, which arises in an immune-suppressive environment.

Imaging Adipose Tissue Browning using Mitochondrial Complex-I Tracer [F]BCPP-EF.

Browning of white adipose tissue (WAT) into beige adipocytes has been proposed as a strategy to tackle the ongoing obesity epidemic. Thermogenic stimuli have been investigated with the aim of converting existing white adipose tissue, primarily used for energy storage, into beige adipocytes capable of dissipating energy; however, evaluation is complicated by the dearth of noninvasive methodologies to quantify beige adipocytes in WAT. Imaging with [F]FDG is commonly used to measure brown adipose tissue (BAT) and beige adipocytes but the relationship between beige adipocytes, thermogenesis and [F]FDG uptake is unclear.

Imaging Kv1.3 Expressing Memory T Cells as a Marker of Immunotherapy Response.

Immune checkpoint inhibitors have shown great promise, emerging as a new pillar of treatment for cancer; however, only a relatively small proportion of recipients show a durable response to treatment. Strategies that reliably differentiate durably-responding tumours from non-responsive tumours are a critical unmet need. Persistent and durable immunological responses are associated with the generation of memory T cells.

Early detection of community acquired of SARS-CoV-2 lineage B.1.351 in Hong Kong.

Background: Prior to this report, variants of concern for SARS-CoV-2 were only detected from imported cases in Hong Kong.

Objective: Multiple cases of SARS-CoV-2 lineage B.1.

Discovery of a Partial Glucokinase Activator Clinical Candidate: Diethyl ((3-(3-((5-(Azetidine-1-carbonyl)pyrazin-2-yl)oxy)-5-isopropoxybenzamido)-1-pyrazol-1-yl)methyl)phosphonate (BMS-820132).

Glucokinase (GK) is a key regulator of glucose homeostasis, and its small-molecule activators represent a promising opportunity for the treatment of type 2 diabetes. Several GK activators have been advanced into clinical trials and have demonstrated promising efficacy; however, hypoglycemia represents a key risk for this mechanism. In an effort to mitigate this hypoglycemia risk while maintaining the efficacy of the GK mechanism, we have investigated a series of amino heteroaryl phosphonate benzamides as ''partial" GK activators.