Abstract Objective This study aims to accurately classify ATN profiles using highly specific amyloid and tau PET ligands and MRI in patients with cognitive impairment and suspected Alzheimer’s disease (AD). It also aims to explore the relationship between quantified amyloid and tau deposition and cognitive function. Methods Twenty-seven patients (15 women and 12 men; age range: 64–81 years) were included in this study. Amyloid and tau PET scans were performed using 18F-NAV4694 and 18F-MK6240, respectively. For each patient, amyloid and tau PET images were visually assessed and classified as either amyloid-positive or amyloid-negative, and as 18F-MK6240 Braak stage 0 (tau-negative) or Braak stages I–VI (tau-positive). Voxel-based morphometry of three-dimensional T1-weighted MRI was used to evaluate neurodegeneration. Amyloid and tau depositions were quantified using the Centiloid scale and standardized uptake value ratio (SUVR), respectively. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Results Patients were categorized into seven ATN profiles. Six patients (22%) exhibited a normal AD biomarker profile, 15 patients (56%) fell within the Alzheimer’s continuum, and 14 patients (52%) were diagnosed with AD. Additionally, six patients (22%) displayed non-AD pathological changes. Positive and negative findings of amyloid and tau PET were concordant in 24 patients (89%). Among the 14 patients diagnosed with AD, the Centiloid scale for amyloid deposition did not show a significant negative correlation with MMSE scores (r = 0.269, p = 0.451). In contrast, the SUVR for tau deposition in the neocortex exhibited a significant negative correlation (r = −0.689, p = 0.014), while tau deposition in the mesial temporal region did not show a significant correlation (r = 0.158, p = 0.763). Conclusion Highly specific amyloid and tau PET scans, along with MRI, can be utilized to accurately classify ATN profiles in patients with cognitive impairment and suspected AD. The discordance in amyloid and tau PET findings in three patients allowed for a more precise AD diagnosis. Furthermore, tau PET imaging provided insight into the propagation of tau deposition in the neocortex beyond the mesial temporal region, which is associated with cognitive decline.

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Abstract Big cats are of conservation concern throughout their range, and genetic tools are often employed to study them for various purposes. However, there are several difficulties in using genetic tools for big cat conservation that could be resolved by modern methods of DNA sequencing. Recent reports of the sighting of a putative Javan tiger Panthera tigris sondaica in West Java, Indonesia, highlight some of the difficulties of studying the genetics of big cats. We reanalysed the data of the original reports and found that the conclusions were drawn based on incorrect copies of the genes. Specifically, the nuclear copy of the mitochondrial gene was analysed with the mitochondrial sequence, leading to discordance in the results. However, re-sequencing of the remaining DNA confirms that the sighting could have been that of a tiger, but the subspecies cannot be confirmed. This work highlights the urgency of developing high-throughput sequencing infrastructure in the tropics and the need for reliable databases for the study of big cats.

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ABSTRACTHutchinson‐Gilford progeria syndrome (HGPS) is a premature aging disease caused by progerin, a mutant variant of lamin A. Progerin anchors aberrantly to the nuclear envelope disrupting a plethora of cellular processes, which in turn elicits senescence. We previously showed that the chromosomal region maintenance 1 (CRM1)‐driven nuclear export pathway is abnormally enhanced in patient‐derived fibroblasts, due to overexpression of CRM1. Interestingly, pharmacological inhibition of CRM1 using leptomycin B rescues the senescent phenotype of HGPS fibroblasts, delineating CRM1 as a potential therapeutic target against HGPS. As a proof of concept, we analyzed the beneficial effects of pharmacologically modulating CRM1 in dermal fibroblasts from HGPS patients and the LMNAG609G/G609G mouse, using the first‐in‐class selective inhibitor of CRM1 termed selinexor. Remarkably, treatment of HGPS fibroblasts with selinexor mitigated senescence and promoted progerin clearance via autophagy, while at the transcriptional level restored the expression of numerous differentially‐expressed genes and rescued cellular processes linked to aging. In vivo, oral administration of selinexor to the progeric mouse resulted in decreased progerin immunostaining in the liver and aorta, decreased progerin levels in most liver, lung and kidney samples analyzed by immunoblotting, and improved aortic histopathology. Collectively our data indicate that selinexor exerts its geroprotective action by at least two mechanisms: normalizing the nucleocytoplasmic partition of proteins with a downstream effect on the aging‐associated transcriptome and decreasing progerin levels. Further investigation of the overall effect of selinexor on LmnaG609G/G609G mouse physiology, with emphasis in cardiovascular function is warranted, to determine its therapeutic utility for HGPS and aging‐associated disorders characterized by CRM1 overactivity.

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Adalimumab, a monoclonal antibody used for treating inflammatory diseases, including eye diseases, faces challenges in biodistribution and targeted delivery. Nanoparticle (NP)‐based drug delivery systems have shown promise in enhancing the pharmacokinetic profiles of biologic drugs. This study aims to develop, and characterize intravitreal adalimumab‐loaded poly(lactic‐co‐glycolic acid) (PLGA) NPs to improve antibody distribution and therapeutic efficacy. Characterization studies, morphological examination, and quantitative, stability, and physical properties are conducted. In vitro release kinetics are assessed using a dialysis membrane method. In vivo biodistribution is studied in rats after intravitreal administration by Positron Emission Tomography/Computed Tomography imaging. The optimized NPs were spherical (around 300 nm) with a surface charge of about −20 mV. Encapsulation efficiency and drug loading reach values close to 100%. Stability studies showed minimal changes in particle size and drug content. In vitro release showed a biphasic pattern with an initial burst release followed by sustained release. Safety studies indicated no significant cytotoxicity or adverse effects. The adalimumab‐loaded PLGA NPs demonstrate favorable physicochemical characteristics, stability, and release profiles. In vivo distribution revealed a change in the antibody's distribution pattern after intravitreal administration via NPs encapsulation. These findings suggest the potential for enhanced therapeutic outcomes and warrant further investigation in disease‐specific models to explore the clinical potential of this NP‐based delivery system.

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AbstractPhotonics bound states in the continuum (BICs) are peculiar localized states in the continuum of free‐space waves, unaffected by far‐field radiation loss. Although plasmonic nano‐antennas squeeze the optical field to nanoscale volumes, engineering the emergence of quasi‐BICs with plasmonic hotspots remains challenging. Here, the origin of symmetry‐protected (SP) quasi‐BICs in a 2D system of silver‐filled dimers, quasi‐embedded in a high‐index dielectric waveguide, is investigated through the strong coupling between photonic and plasmonic modes. By tailoring the hybridizing plasmonic/photonic fractions, a trade‐off is selected at which the quasi‐BIC exhibits both high intrinsic Q‐factor and strong near‐field enhancement because of dimer‐gap hotspot activation. Not only radiation loss is damped but in a configuration sustaining a lattice of plasmonic hotspots. This leads to an advantageous small modal volume for enhancing light‐matter interaction. The layout of nearly embedded dimers is designed to maximize the spatial overlap between the optical field and the target molecules, enhancing reactive sensing efficiency. The architecture is evaluated for its ability to detect transactive response DNA‐binding protein 43. The refractometric sensitivity outperforms current label‐free biosensing platforms, reaching the zeptomolar range. The approach highlights the potential of combining plasmonic and dielectric nanomaterials for advanced sensing technologies.

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