Developing Predictive Molecular Maps of Human Disease through Community-based Modeling

The failure of biology to identify the molecular causes of disease has led to disappointment in the rate of development of new medicines. By combining the power of community-based modeling with broad access to large datasets on a platform that promotes reproducible analyses we can work towards more predictive molecular maps that can deliver better therapeutics

The mPower Study, Parkinson Disease Mobile Data Collected Using Researchkit

Current measures of health and disease are often insensitive, episodic, and subjective. Further, these measures generally are not designed to provide meaningful feedback to individuals. The impact of high-resolution activity data collected from mobile phones is only beginning to be explored. Here we present data from mPower, a clinical observational study about Parkinson disease conducted purely through an iPhone app interface. The study interrogated aspects of this movement disorder through surveys and frequent sensor-based recordings from participants with and without Parkinson disease. Benefitting from large enrollment and repeated measurements on many individuals, these data may help establish baseline variability of real-world activity measurement collected via mobile phones, and ultimately may lead to quantification of the ebbs-and-flows of Parkinson symptoms. App source code for these data collection modules are available through an open source license for use in studies of other conditions. We hope that releasing data contributed by engaged research participants will seed a new community of analysts working collaboratively on understanding mobile health data to advance human health

Disk-Corona Model of Active Galactic Nuclei with Nonthermal Pairs

As a promising model for the X-ray emission from radio-quiet quasars and Seyfert 1 nuclei, we present a nonthermal disk-corona model, where soft photons from a disk are Comptonized by the nonthermal electron-positron pairs in a coronal region above the disk. Various characteristics of our model are qualitatively similar to the homogeneous, spherical, nonthermal pair models previously studied, but the important difference is that in our disk-corona model gamma-ray depletion is far more efficient, and, moreover, the gamma-ray annihilation line is much less prominent. Consequently, this model naturally satisfies the observed constraints on active galactic nuclei

The Association Between Serious Psychological Distress And Life Satisfaction Among U.S Adults With Hypertension

Purpose: Given the observed link between psychosocial and physical health outcomes, this study investigates the association between serious psychological distress and life satisfaction among U.S adults with hypertension. Methods: A cross-sectional study using 2021 National Health Interview Survey data among U.S adults was conducted to investigate the association between serious psychological distress and hypertension and assess the role of life satisfaction in modifying this relationship. Hypertension (diagnosed, undiagnosed), serious psychological distress (≥ 13 on the Kessler 6 nonspecific distress scale), and life satisfaction (Very satisfied, Satisfied, Dissatisfied, Very dissatisfied) were self-reported by participants. Ordinal logistic regression was used to investigate relationships between hypertension, serious psychological distress and life satisfaction. Stratified analysis explored the combined effects of life satisfaction and hypertension on psychological distress, using logistic and ordinal logistic regression Results: The analysis of data represented 253,157,754 U.S adults, revealing a 31.5% prevalence of hypertension in this population. Adjusted ordinal logistic regression models demonstrate a significant association between hypertension and an increased odds of reporting each psychological distress measure, with odds ranging from (OR:1.36-1.48, 95% CI: 1.28-1.65). Hypertension was associated with decreased odds of reporting higher levels of life satisfaction (OR: 0.75, 95% CI: 0.71-0.80). Life dissatisfaction was associated with elevated odds of overall psychological distress (OR: 16.18, 95% CI:12.29-21.28) and each individual distress measure (OR: 4.75-14.24, 95% CI: 3.98-17.36). Furthermore, hypertension exacerbated these associations among individuals reporting life dissatisfaction (OR: 1.41-1.95, 95% CI: 1.10-2.47). A statistically significant interaction between hypertension and life satisfaction was observed for the distress measure “effort” (p=0.0006), indicating a modifying effect of hypertension on the association between life satisfaction and feelings of effort. Conclusion: This study demonstrates significant associations between hypertension and distress. Notably, life dissatisfaction is a strong predictor of serious psychological distress and hypertension can exacerbate these outcomes. Further research is warranted to investigate the associations between psychosocial health and hypertension prevalence

Mass Spectrometry Quantification, Localization, and Discovery of Feeding-Related Neuropeptides in Cancer borealis

The crab Cancer borealis nervous system is an important model for understanding neural circuit dynamics and modulation, but the identity of neuromodulatory substances and their influence on circuit dynamics in this system remains incomplete, particularly with respect to behavioral state-dependent modulation. Therefore, we used a multifaceted mass spectrometry (MS) method to identify neuropeptides that differentiate the unfed and fed states. Duplex stable isotope labeling revealed that the abundance of 80 of 278 identified neuropeptides was distinct in ganglia and/or neurohemal tissue from fed vs unfed animals. MS imaging revealed that an additional 7 and 11 neuropeptides exhibited altered spatial distributions in the brain and the neuroendocrine pericardial organs (POs), respectively, during these two feeding states. Furthermore, de novo sequencing yielded 69 newly identified putative neuropeptides that may influence feeding state-related neuromodulation. Two of these latter neuropeptides were determined to be upregulated in PO tissue from fed crabs, and one of these two peptides influenced heartbeat in ex vivo preparations. Overall, the results presented here identify a cohort of neuropeptides that are poised to influence feeding-related behaviors, providing valuable opportunities for future functional studies

RadRotator: 3D Rotation of Radiographs with Diffusion Models

Transforming two-dimensional (2D) images into three-dimensional (3D) volumes is a well-known yet challenging problem for the computer vision community. In the medical domain, a few previous studies attempted to convert two or more input radiographs into computed tomography (CT) volumes. Following their effort, we introduce a diffusion model-based technology that can rotate the anatomical content of any input radiograph in 3D space, potentially enabling the visualization of the entire anatomical content of the radiograph from any viewpoint in 3D. Similar to previous studies, we used CT volumes to create Digitally Reconstructed Radiographs (DRRs) as the training data for our model. However, we addressed two significant limitations encountered in previous studies: 1. We utilized conditional diffusion models with classifier-free guidance instead of Generative Adversarial Networks (GANs) to achieve higher mode coverage and improved output image quality, with the only trade-off being slower inference time, which is often less critical in medical applications; and 2. We demonstrated that the unreliable output of style transfer deep learning (DL) models, such as Cycle-GAN, to transfer the style of actual radiographs to DRRs could be replaced with a simple yet effective training transformation that randomly changes the pixel intensity histograms of the input and ground-truth imaging data during training. This transformation makes the diffusion model agnostic to any distribution variations of the input data pixel intensity, enabling the reliable training of a DL model on input DRRs and applying the exact same model to conventional radiographs (or DRRs) during inference.Comment: Website: https://pouriarouzrokh.github.io/RadRotator Online demo: https://huggingface.co/spaces/Pouriarouzrokh/RadRotator Article information: 16 pages, 11 figure

Secondary nucleating sequences affect kinetics and thermodynamics of tau aggregation

Tau protein was scanned for highly amyloidogenic sequences in amphiphilic motifs (X)nZ, Z(X)nZ (n≥2) or (XZ)n (n≥2), where X is a hydrophobic residue and Z is a charged or polar residue. N-acetyl peptides homologous to these sequences were used to study aggregation. Transmission electron microscopy (TEM) showed 7 peptides, in addition to well known primary nucleating sequences c275VQIINK (AcPHF6*) and Ac306VQIVYK (AcPHF6), formed fibers, tubes, ribbons or rolled sheets. Of the peptides shown by TEM to form amyloid, Ac10VME, AcPHF6*, Ac375KLTFR, and Ac393VYK were found to enhance the fraction of β-structure of AcPHF6 formed at equilibrium, and Ac375KLTFR was found to inhibit AcPHF6 and AcPHF6* aggregation kinetics in a dose-dependent manner, consistent with its participation in a hybrid steric zipper model. Single site mutants were generated which transformed predicted amyloidogenic sequences in tau into non-amyloidogenic ones. A M11K mutant had fewer filaments and showed a decrease in aggregation kinetics and an increased lag time compared to wild type tau, while a F378K mutant showed significantly more filaments. Our results infer that sequences throughout tau, in addition to PHF6 and PHF6*, can seed amyloid formation or affect aggregation kinetics or thermodynamics

Laboratory Selection Quickly Erases Historical Differentiation

The roles of history, chance and selection have long been debated in evolutionary biology. Though uniform selection is expected to lead to convergent evolution between populations, contrasting histories and chance events might prevent them from attaining the same adaptive state, rendering evolution somewhat unpredictable. The predictability of evolution has been supported by several studies documenting repeatable adaptive radiations and convergence in both nature and laboratory. However, other studies suggest divergence among populations adapting to the same environment. Despite the relevance of this issue, empirical data is lacking for real-time adaptation of sexual populations with deeply divergent histories and ample standing genetic variation across fitness-related traits. Here we analyse the real-time evolutionary dynamics of Drosophila subobscura populations, previously differentiated along the European cline, when colonizing a new common environment. By analysing several life-history, physiological and morphological traits, we show that populations quickly converge to the same adaptive state through different evolutionary paths. In contrast with other studies, all analysed traits fully converged regardless of their association with fitness. Selection was able to erase the signature of history in highly differentiated populations after just a short number of generations, leading to consistent patterns of convergent evolution

Clinton Street MAX Visioning

This report documents the initial analysis and visioning process performed in the area surrounding the Clinton Street Station, which is nestled between Hosford-Abernethy and Brooklyn neighborhoods and the Central Eastside Industrial District. This project focuses on the future of the Clinton Street Station and how its development will impact the surrounding area over the next 50 years. This task involved acknowledging and balancing the current needs of the various stakeholders. The purpose of this report is to act as a tool for the Hosford-Abernethy Neighborhood Association (HAND) to more adequately understand the opportunities and constraints that the future station area holds. In order to begin imagining the future of the area, a thorough understanding and analysis is presented. Following this, design principles that shape the vision for the future are described. The document concludes with next steps and implementation recommendations. This project was conducted under the supervision of Donald J. Stastny and Edward Starkie