LATE-NC staging in routine neuropathologic diagnosis: An update

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer\u27s disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience

FAST: FAST Analysis of Sequences Toolbox.

FAST (FAST Analysis of Sequences Toolbox) provides simple, powerful open source command-line tools to filter, transform, annotate and analyze biological sequence data. Modeled after the GNU (GNU's Not Unix) Textutils such as grep, cut, and tr, FAST tools such as fasgrep, fascut, and fastr make it easy to rapidly prototype expressive bioinformatic workflows in a compact and generic command vocabulary. Compact combinatorial encoding of data workflows with FAST commands can simplify the documentation and reproducibility of bioinformatic protocols, supporting better transparency in biological data science. Interface self-consistency and conformity with conventions of GNU, Matlab, Perl, BioPerl, R, and GenBank help make FAST easy and rewarding to learn. FAST automates numerical, taxonomic, and text-based sorting, selection and transformation of sequence records and alignment sites based on content, index ranges, descriptive tags, annotated features, and in-line calculated analytics, including composition and codon usage. Automated content- and feature-based extraction of sites and support for molecular population genetic statistics make FAST useful for molecular evolutionary analysis. FAST is portable, easy to install and secure thanks to the relative maturity of its Perl and BioPerl foundations, with stable releases posted to CPAN. Development as well as a publicly accessible Cookbook and Wiki are available on the FAST GitHub repository at https://github.com/tlawrence3/FAST. The default data exchange format in FAST is Multi-FastA (specifically, a restriction of BioPerl FastA format). Sanger and Illumina 1.8+ FastQ formatted files are also supported. FAST makes it easier for non-programmer biologists to interactively investigate and control biological data at the speed of thought

Estimating the Material Properties of Fabric from Video

Passively estimating the intrinsic material properties of deformable objects moving in a natural environment is essential for scene understanding. We present a framework to automatically analyze videos of fabrics moving under various unknown wind forces, and recover two key material properties of the fabric: stiffness and area weight. We extend features previously developed to compactly represent static image textures to describe video textures, such as fabric motion. A discriminatively trained regression model is then used to predict the physical properties of fabric from these features. The success of our model is demonstrated on a new, publicly available database of fabric videos with corresponding measured ground truth material properties. We show that our predictions are well correlated with ground truth measurements of stiffness and density for the fabrics. Our contributions include: (a) a database that can be used for training and testing algorithms for passively predicting fabric properties from video, (b) an algorithm for predicting the material properties of fabric from a video, and (c) a perceptual study of humans' ability to estimate the material properties of fabric from videos and images.National Science Foundation (U.S.) (CGV-1111415)National Science Foundation (U.S.) (CGV-1212928)National Science Foundation (U.S.). Graduate Research FellowshipMassachusetts Institute of Technology (Intelligent Initiative Postdoctoral Fellowship)United States. Intelligence Advanced Research Projects Activity (D10PC20023

MicroRNA Expression Patterns in Human Anterior Cingulate and Motor Cortex: A Study of Dementia with Lewy Bodies Cases and Controls

Overview MicroRNAs (miRNAs) have been implicated in neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease (AD). Here, we evaluated the expression of miRNAs in anterior cingulate (AC; Brodmann area [BA] 24) and primary motor (MO; BA 4) cortical tissue from aged human brains in the University of Kentucky AD Center autopsy cohort, with a focus on dementia with Lewy bodies (DLB). Methods RNA was isolated from gray matter of brain samples with pathology-defined DLB, AD, AD+DLB, and low-pathology controls, with n=52 cases initially included (n=23 with DLB), all with low (\u3c4hrs) postmortem intervals. RNA was profiled using Exiqon miRNA microarrays. Quantitative PCR for post-hoc replication was performed on separate cases (n=6 controls) and included RNA isolated from gray matter of MO, AC, primary somatosensory (BA 3), and dorsolateral prefrontal (BA 9) cortical regions. Results The miRNA expression patterns differed substantially according to anatomic location: of the relatively highly-expressed miRNAs, 150/481 (31%) showed expression that was different between AC versus MO (at p\u3c0.05 following correction for multiple comparisons), most (79%) with higher expression in MO. A subset of these results were confirmed in qPCR validation focusing on miR-7, miR-153, miR-133b, miR-137, and miR-34a. No significant variation in miRNA expression was detected in association with either neuropathology or sex after correction for multiple comparisons. Conclusion A subset of miRNAs (some previously associated with α-synucleinopathy and/or directly targeting α-synuclein mRNA) were differentially expressed in AC and MO, which may help explain why these brain regions show differences in vulnerability to Lewy body pathology

Low-energy Bluetooth for Detecting Real-world Penetrance of Bystander Naloxone Kits: A Pilot Study

Opioid overdose is a growing public health emergency in the United States. The antidote naloxone must be administered rapidly after opioid overdose to prevent death. Bystander or take-home naloxone programs distribute naloxone to opioid users and other community members to increase naloxone availability at the time of overdose. However, data describing the natural history of take- home naloxone in the hands of at-risk individuals is lacking. To understand patterns of naloxone uptake in at-risk users, we developed a smart naloxone kit that uses low-energy Bluetooth (BLE) to unobtrusively detect the transit of naloxone through a hospital campus. In this paper, we describe development of the smart naloxone kit and results from the first 10 participants in our pilot study

Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1) formulated with the adjuvant IC31, was evaluated in HIV-infected adults. METHODS: HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay. RESULTS: 47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015). Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells. CONCLUSION: H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR) PACTR201105000289276

A Distance-Weighted Interaction Map Reveals a Previously Uncharacterized Layer of the Bacillus subtilis Spore Coat

SummaryBacillus subtilis spores are encased in a protein assembly called the spore coat that is made up of at least 70 different proteins. Conventional electron microscopy shows the coat to be organized into two distinct layers. Because the coat is about as wide as the theoretical limit of light microscopy, quantitatively measuring the localization of individual coat proteins within the coat is challenging. We used fusions of coat proteins to green fluorescent protein to map genetic dependencies for coat assembly and to define three independent subnetworks of coat proteins. To complement the genetic data, we measured coat protein localization at subpixel resolution and integrated these two data sets to produce a distance-weighted genetic interaction map. Using these data, we predict that the coat comprises at least four spatially distinct layers, including a previously uncharacterized glycoprotein outermost layer that we name the spore crust. We found that crust assembly depends on proteins we predicted to localize to the crust. The crust may be conserved in all Bacillus spores and may play critical functions in the environment

Efficacy of compost amended biofiltration swales as green stormwater infrastructure for treatment of toxicants in Salish Sea road run-off

Biofiltration swales, or bioswales, use vegetated soil substrates to filter contaminants from stormwater, decrease sediment load, and reduce erosion. Following a storm, runoff moves slowly through the swale at a shallow depth. While stormwater is retained in the bioswales, pollutants are removed by the combined effects of filtration, infiltration, settling, and biotransformation. The system currently being evaluated at the Washington State University (WSU) Puyallup Research and Extension Center (PREC) uses compost to further enhance the ability of bioswales to remove toxicants. WSDOT has created guidelines for constructing compost amended biofiltration swales (CABS) and implemented a field test for CABS along Washington State Route (SR) 518 in 2009. As part of an ongoing study, influent and effluent samples are currently being collected at the field site during storm events and tested for metals, PAHs, pesticides, phthalates, and unknowns (LC-QTOF). Acute toxicity and sub-lethal effects of stormwater were also measured using zebrafish (Danio rerio) bioassays. Along with researchers from University of Washington (UW) we created a laboratory model for CABS at the WSU PREC to verify field test results in a controlled setting and identify ways that the WSDOT design could be improved. This system is exposed to highway runoff from a previously studied high volume source off SR 520 and tested at different flow rates, swale lengths, and slope gradients. Paired chemistry and toxicology data show how stormwater treatment by CABS differ from traditional soil biofiltration methods. Results presented at Salish Sea show how zebrafish developmental biology is affected by stormwater treatments and how CABS design impacts toxicant treatment efficacy

Global and Regional Estimates of Prevalent and Incident Herpes Simplex Virus Type 1 Infections in 2012

Herpes simplex virus type 1 (HSV-1) commonly causes orolabial ulcers, while HSV-2 commonly causes genital ulcers. However, HSV-1 is an increasing cause of genital infection. Previously, the World Health Organization estimated the global burden of HSV-2 for 2003 and for 2012. The global burden of HSV-1 has not been estimated.We fitted a constant-incidence model to pooled HSV-1 prevalence data from literature searches for 6 World Health Organization regions and used 2012 population data to derive global numbers of 0-49-year-olds with prevalent and incident HSV-1 infection. To estimate genital HSV-1, we applied values for the proportion of incident infections that are genital.We estimated that 3709 million people (range: 3440-3878 million) aged 0-49 years had prevalent HSV-1 infection in 2012 (67%), with highest prevalence in Africa, South-East Asia and Western Pacific. Assuming 50% of incident infections among 15-49-year-olds are genital, an estimated 140 million (range: 67-212 million) people had prevalent genital HSV-1 infection, most of which occurred in the Americas, Europe and Western Pacific.The global burden of HSV-1 infection is huge. Genital HSV-1 burden can be substantial but varies widely by region. Future control efforts, including development of HSV vaccines, should consider the epidemiology of HSV-1 in addition to HSV-2, and especially the relative contribution of HSV-1 to genital infection