Association Between Sedentary Time and Quality of Life From the Osteoarthritis Initiative: Who Might Benefit Most From Treatment?

Objective To investigate the relationship between sedentary behavior and quality-adjusted life years (QALYs) among participants in the Osteoarthritis Initiative. Design Longitudinal, observational design. Setting Osteoarthritis Initiative cohort. Participants Individuals (N=1794) from a prospective, multicenter longitudinal cohort were classified into quantile groups based on average daily sedentary time (most sedentary, quartile 1 [Q1] ≥11.6h; 10.7h≤ Q2 Interventions Not applicable. Main Outcome Measures Individual QALYs were estimated over 2 years from the area under the curve of health-related utility scores derived from the Medical Outcomes Study 12-Item Short-Form Health Survey versus time. The relationship between baseline sedentary behavior and median 2-year QALYs was estimated using quantile regression adjusted for socioeconomic factors and body mass index. Results Lower QALYs over 2 years were more frequently found among the most sedentary (Q1, median 1.59), and QALYs increased as time spent in baseline sedentary behavior decreased (median QALYs for Q2, 1.64; Q3, 1.65; Q4, 1.65). The relationship of sedentary time and median QALY change was only significant for the most sedentary Q1 group, where an additional hour of sedentary behavior significantly reduced QALYs by −.072 (95% confidence interval, −.121 to −.020). Conclusions Our findings suggest that individuals with the most extreme sedentary profiles may be vulnerable to additional losses of quality of life if they become more sedentary. Targeting these individuals to decrease sedentary behavior has the potential to be cost-effective

Identifying metabolites from protein identifiers with P2M

The identification of metabolites from complex biological samples often involves matching experimental mass spectrometry data to signatures of compounds derived from massive chemical databases. However, misidentifications may result due to the complexity of potential chemical space that leads to databases containing compounds with nearly identical structures. Prior knowledge of compounds that may be enzymatically consumed or produced by an organism can help reduce misidentifications by restricting initial database searching to compounds that are likely to be present in a biological system. While databases such as UniProt allow for the identification of small molecules that may be consumed or generated by enzymes encoded in an organism's genome, currently no tool exists for identifying SMILES strings of metabolites associated with protein identifiers and expanding R-containing substructures to fully defined, biologically relevant chemical structures. Here we present Proteome2Metabolome (P2M), a tool that performs these tasks using external database querying behind a simple command line interface. Beyond mass spectrometry based applications, P2M can be generally used to identify biologically relevant chemical structures likely to be observed in a biological system

Physical Activity Minimum Threshold Predicting Improved Function in Adults With Lower‐Extremity Symptoms

Objective To identify an evidence‐based minimum physical activity threshold to predict improved or sustained high function for adults with lower‐extremity joint symptoms. Methods Prospective multisite data from 1,629 adults, age ≥49 years with symptomatic lower‐extremity joint pain/aching/stiffness, participating in the Osteoarthritis Initiative accelerometer monitoring substudy were clinically assessed 2 years apart. Improved/high function in 2‐year gait speed and patient‐reported outcomes (PROs) were based on improving or remaining in the best (i.e., maintaining high) function quintile compared to baseline status. Optimal thresholds predicting improved/high function were investigated using classification trees for the legacy federal guideline metric requiring 150 minutes/week of moderate‐vigorous (MV) activity in bouts lasting 10 minutes or more (MV‐bout) and other metrics (total MV, sedentary, light intensity activity, nonsedentary minutes/week). Results Optimal thresholds based on total MV minutes/week predicted improved/high function outcomes more strongly than the legacy or other investigated metrics. Meeting the 45 total MV minutes/week threshold had increased relative risk (RR) for improved/high function (gait speed RR 1.8, 95% confidence interval [95% CI] 1.6, 2.1 and PRO physical function RR 1.4, 95% CI 1.3, 1.6) compared to less active adults. Thresholds were consistent across sex, body mass index, knee osteoarthritis status, and age. Conclusion These results supported a physical activity minimum threshold of 45 total MV minutes/week to promote improved or sustained high function for adults with lower‐extremity joint symptoms. This evidence‐based threshold is less rigorous than federal guidelines (≥150 MV‐bout minutes/week) and provides an intermediate goal towards the federal guideline for adults with lower‐extremity symptoms

Integrative analysis identifies candidate tumor microenvironment and intracellular signaling pathways that define tumor heterogeneity in NF1

Neurofibromatosis type 1 (NF1) is a monogenic syndrome that gives rise to numerous symptoms including cognitive impairment, skeletal abnormalities, and growth of benign nerve sheath tumors. Nearly all NF1 patients develop cutaneous neurofibromas (cNFs), which occur on the skin surface, whereas 40-60% of patients develop plexiform neurofibromas (pNFs), which are deeply embedded in the peripheral nerves. Patients with pNFs have a ~10% lifetime chance of these tumors becoming malignant peripheral nerve sheath tumors (MPNSTs). These tumors have a severe prognosis and few treatment options other than surgery. Given the lack of therapeutic options available to patients with these tumors, identification of druggable pathways or other key molecular features could aid ongoing therapeutic discovery studies. In this work, we used statistical and machine learning methods to analyze 77 NF1 tumors with genomic data to characterize key signaling pathways that distinguish these tumors and identify candidates for drug development. We identified subsets of latent gene expression variables that may be important in the identification and etiology of cNFs, pNFs, other neurofibromas, and MPNSTs. Furthermore, we characterized the association between these latent variables and genetic variants, immune deconvolution predictions, and protein activity predictions

Systematic Assessment of Retrieval Methods for Canopy Far-Red Solar-Induced Chlorophyll Fluorescence Using High-Frequency Automated Field Spectroscopy

Remote sensing of solar‐induced chlorophyll fluorescence (SIF) offers potential to infer photosynthesis across scales and biomes. Many retrieval methods have been developed to estimate top‐of‐canopy SIF using ground‐based spectroscopy. However, inconsistencies among methods may confound interpretation of SIF dynamics, eco‐physiological/environmental drivers, and its relationship with photosynthesis. Using high temporal‐ and spectral resolution ground‐based spectroscopy, we aimed to (1) evaluate performance of SIF retrieval methods under diverse sky conditions using continuous field measurements; (2) assess method sensitivity to fluctuating light, reflectance, and fluorescence emission spectra; and (3) inform users for optimal ground‐based SIF retrieval. Analysis included field measurements from bi‐hemispherical and hemispherical‐conical systems and synthetic upwelling radiance constructed from measured downwelling radiance, simulated reflectance, and simulated fluorescence for benchmarking. Fraunhofer‐based differential optical absorption spectroscopy (DOAS) and singular vector decomposition (SVD) retrievals exhibit convergent SIF‐PAR relationships and diurnal consistency across different sky conditions, while O₂A‐based spectral fitting method (SFM), SVD, and modified Fraunhofer line discrimination (3FLD) exhibit divergent SIF‐PAR relationships across sky conditions. Such behavior holds across system configurations, though hemispherical‐conical systems diverge less across sky conditions. O₂A retrieval accuracy, influenced by atmospheric distortion, improves with a narrower fitting window and when training SVD with temporally local spectra. This may impact SIF‐photosynthesis relationships interpreted by previous studies using O₂A‐based retrievals with standard (759–767.76 nm) fitting windows. Fraunhofer‐based retrievals resist atmospheric impacts but are noisier and more sensitive to assumed SIF spectral shape than O₂A‐based retrievals. We recommend SVD or SFM using reduced fitting window (759.5–761.5 nm) for robust far‐red SIF retrievals across sky conditions

Real time patient-reported outcome measures in patients with cancer: Early experience within an integrated health system

BACKGROUND: While patient-reported outcome measures (PROMs) have benefit in cancer clinical trials, real-world applications are lacking. This study describes the method of implementation of a cancer enterprise-wide PROMs platform. METHODS: After establishing a multispecialty stakeholder group within a large integrated health system, domain-specific instruments were selected from the National Institutes of Health\u27s Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (pain interference, fatigue, physical function, and depression) and were administered at varying frequencies throughout each patient\u27s cancer journey. All cancer patients with an oncologic visit were eligible to complete the PROMs prior to the visit using a patient portal, or at the time of the visit using a tablet. PROMs were integrated into clinical workflow. Clinical partnerships were essential for successful implementation. Descriptive preliminary data were compared using multivariable logistic regression to determine the factors associated with method of PROMs completion. RESULTS: From September 16, 2020 to July 23, 2021, 23 of 38 clinical units (60.5%) implemented PROMs over 2392 encounters and 1666 patients. Approximately one third of patients (n = 629, 37.8%) used the patient portal. Black patients (aOR 0.70; 95% CI: 0.51-0.97) and patients residing in zip codes with higher percentage of unemployment (aOR: 0.07, 95% CI: 0.01-0.41) were among the least likely to complete PROMs using the patient portal. CONCLUSIONS: Successful system-wide implementation of PROMs among cancer patients requires engagement from multispecialty stakeholders and investment from clinical partners. Attention to the method of PROMs collection is required in order to reduce the potential for disparities, such as Black populations and those residing in areas with high levels of unemployment

Pathologic gene network rewiring implicates PPP1R3A as a central regulator in pressure overload heart failure

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and perturbed respiratory metabolism. Mice lacking PPP1R3A are protected against pressure-overload heart failure. We present a global gene interaction map of the human heart failure transition, identify previously unreported cardiac eQTLs, and demonstrate the discovery potential of disease-specific networks through the description of PPP1R3A as a central regulator in heart failure

A Randomized Trial of a Motivational Interviewing Intervention to Increase Lifestyle Physical Activity and Improve Self-Reported Function in Adults with Arthritis

Background Arthritis is a leading cause of chronic pain and functional limitations. Exercise is beneficial for improving strength and function and decreasing pain. We evaluated the effect of a motivational interviewing-based lifestyle physical activity intervention on self-reported physical function in adults with knee osteoarthritis (KOA) or rheumatoid arthritis (RA). Methods Participants were randomized to intervention or control. Control participants received a brief physician recommendation to increase physical activity to meet national guidelines. Intervention participants received the same brief baseline physician recommendation in addition to motivational interviewing sessions at baseline, 3, 6, and 12 months. These sessions focused on facilitating individualized lifestyle physical activity goal setting. The primary outcome was change in self-reported physical function. Secondary outcomes were self-reported pain and accelerometer-measured physical activity. Self-reported KOA outcomes were evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for KOA (WOMAC scores range from 0 to 68 for function and 0 to 20 for pain) and the Health Assessment Questionnaire (HAQ) for RA. Outcomes were measured at baseline, 3, 6, 12, and 24 months. Multiple regression accounting for repeated measures was used to evaluate the overall intervention effect on outcomes controlling for baseline values. Results Participants included 155 adults with KOA (76 intervention and 79 control) and 185 adults with RA (93 intervention and 92 control). Among KOA participants, WOMAC physical function improvement was greater in the intervention group compared to the control group [difference = 2.21 (95% CI: 0.01, 4.41)]. WOMAC pain improvement was greater in the intervention group compared to the control group [difference = 0.70 (95% CI: −0.004, 1.41)]. There were no significant changes in physical activity. Among RA participants, no significant intervention effects were found. Conclusion Participants with KOA receiving the lifestyle intervention experienced modest improvement in self-reported function and a trend toward improved pain compared to controls. There was no intervention effect for RA participants. Further refinement of this intervention is needed for more robust improvement in function, pain, and physical activity

Why accumulation mode organic electrochemical transistors turn off much faster than they turn on

Understanding the factors underpinning device switching times is crucial for the implementation of organic electrochemical transistors (OECTs) in neuromorphic computing and real-time sensing applications. Existing models of device operation cannot explain the experimental observations that turn-off times are generally much faster than turn-on times in accumulation mode OECTs. Through operando optical microscopy, we image the local doping level of the transistor channel and show that device turn-on occurs in two stages, while turn-off occurs in one stage. We attribute the faster turn-off to a combination of engineering as well as physical and chemical factors including channel geometry, differences in doping and dedoping kinetics, and the physical phenomena of carrier density-dependent mobility. We show that ion transport is limiting the device operation speed in our model devices. Our study provides insights into the kinetics of OECTs and guidelines for engineering faster OECTs