Highly-Scalable Searchable Symmetric Encryption with Support for Boolean Queries

This work presents the design, analysis and implementation of the first sub-linear searchable symmetric encryption (SSE) protocol that supports conjunctive search and general Boolean queries on symmetrically-encrypted data and that scales to very large data sets and arbitrarilystructured data including free text search. To date, work in this area has focused mainly on single-keyword search. For the case of conjunctive search, prior SSE constructions required work linear in the total number of documents in the database and provided good privacy only for structured attribute-value data, rendering these solutions too slow and inflexible for large practical databases. In contrast, our solution provides a realistic and practical trade-off between performance and privacy by efficiently supporting very large databases at the cost of moderate and welldefined leakage to the outsourced server (leakage is in the form of data access patterns, never as direct exposure of plaintext data or searched values). A key aspect of our protocols is that it allows the searcherto pivot its conjunctive search on the estimated least frequent keywordin the conjunction. We show that a decisional Diffie-Hellman (DDH) based pseudo-random functio

Supplementary Material for: Tracking Cognitive Decline in Amnestic Mild Cognitive Impairment and Early-Stage Alzheimer Dementia: Mini-Mental State Examination versus Neuropsychological Battery

<p><b><i>Background/Aims:</i></b> Although the Mini-Mental State Examination (MMSE), Clinical Dementia Rating-Sum of Boxes (CDR-SOB), and neuropsychological batteries are widely used for evaluating cognitive function, it remains elusive which instrument best reflects the longitudinal disease progression in amnestic mild cognitive impairment (aMCI) and probable Alzheimer disease (AD). We investigated whether changes in these three instruments over time correlate with loss of cortical gray matter volume (cGMV). <b><i>Methods:</i></b> We retrospectively investigated 204 patients (aMCI, <i>n</i> = 114; AD, <i>n</i> = 90) who had undergone MMSE, CDR-SOB, the dementia version of the Seoul Neuropsychological Screening Battery (SNSB-D), and 3-dimensional T1-weighted magnetic resonance images at least twice. We investigated the partial correlation between annual decline in test scores and percent change of cGMV. <b><i>Results:</i></b> In aMCI patients, changes in the SNSB-D total score (<i>r</i> = 0.340, <i>p</i> < 0.001) and CDR-SOB (<i>r</i> = 0.222, <i>p</i> = 0.020), but not MMSE, showed a correlation with cGMV loss, with the SNSB-D total score showing the strongest correlation. In AD patients, decline in all three test scores correlated significantly with cGMV loss, with MMSE exhibiting the strongest correlation (<i>r</i> = 0.464, <i>p</i> < 0.001). <b><i>Conclusion:</i></b> In aMCI patients, neuropsychological battery, though time-consuming, was the most adequate tool in tracking disease progression. In AD patients, however, MMSE may be the most effective longitudinal monitoring tool when considering cost-effectiveness.</p

Pharmacokinetics and tissue distribution of B-domain deleted recombinant human factor VIII (GC-γ AHF) in rats

Recombinant human factor VIII is a glycoprotein that is used for the treatment of hemophilia A. The B-domain deleted recombinant factor VIII, GC-γ AHF, was newly developed by the Korea Green Cross Pharmaceutical Company. To investigate its pharmacokinetics and tissue distribution, GC-γ AHF was labelled with 125I. Following a single intravenous administration of [125I]GC-γ AHF to rats, plasma concentrations of [125I]GC-γ AHF versus time curves were analyzed and the pharmacokinetic parameters were estimated. The data obtained from plasma as fitted with a two compartment open model and mean residence time (MRT) was 123.83 min. The half life of radioactivity associated with [125I]GC-γ AHF in plasma was 13.25 min and other pharmacokinetic parameters of GC-γ AHF were as follows: Clearance, 23 ml/min/kg; steady-state volume of distribution, 2.84 l/kg. A larger proportion of the administered radioactivity was excreted via urine than via faeces and the total administered dose recovered in excreta was 88.2%. The total levels of radioactivity were higher in liver, stomach and small intestine than in other tissues. These studies suggest that the pharmacokinetic data of GC-γ AHF obtained from rats in the present study would be useful for preclinical evaluation of the newly developed genetically engineered human protein

Fasudil alleviates the vascular endothelial dysfunction and several phenotypes of Fabry disease

Fabry disease (FD), a lysosomal storage disorder, is caused by defective α-galactosidase (GLA) activity, which results in the accumulation of globotriaosylceramide (Gb3) in endothelial cells and leads to life-threatening complications such as left ventricular hypertrophy (LVH), renal failure, and stroke. Enzyme replacement therapy (ERT) results in Gb3 clearance; however, because of a short half-life in the body and the high immunogenicity of FD patients, ERT has a limited therapeutic effect, particularly in patients with late-onset disease or progressive complications. Because vascular endothelial cells (VECs) derived from FD-induced pluripotent stem cells display increased thrombospondin-1 (TSP1) expression and enhanced SMAD2 signaling, we screened for chemical compounds that could downregulate TSP1 and SMAD2 signaling. Fasudil reduced the levels of p-SMAD2 and TSP1 in FD-VECs and increased the expression of angiogenic factors. Furthermore, fasudil downregulated the endothelial-to-mesenchymal transition (EndMT) and mitochondrial function of FD-VECs. Oral administration of fasudil to FD mice alleviated several FD phenotypes, including LVH, renal fibrosis, anhidrosis, and heat insensitivity. Our findings demonstrate that fasudil is a novel candidate for FD therapy. © 2023 The American Society of Gene and Cell Therapy11Nsciescopu

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals