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G-Protein Pathway Suppressor 2 (GPS2) is an inhibitor of non-proteolytic K63 ubiquitination mediated by the E2 ubiquitin-conjugating enzyme Ubc13. Previous studies have associated GPS2-mediated restriction of ubiquitination with the regulation of insulin signaling, inflammatory responses and mitochondria-nuclear communication across different tissues and cell types. However, a detailed understanding of the targets of GPS2/Ubc13 activity is lacking. Here, we have dissected the GPS2-regulated K63 ubiquitome in mouse embryonic fibroblasts and human breast cancer cells, unexpectedly finding an enrichment for proteins involved in RNA binding and translation on the outer mitochondrial membrane. Validation of selected targets of GPS2-mediated regulation, including the RNA-binding protein PABPC1 and translation factors RPS1, RACK1 and eIF3M, revealed a mitochondrial-specific strategy for regulating the translation of nuclear-encoded mitochondrial proteins via non-proteolytic ubiquitination. Removal of GPS2-mediated inhibition, either via genetic deletion or stress-induced nuclear translocation, promotes the import-coupled translation of selected mRNAs leading to the increased expression of an adaptive antioxidant program. In light of GPS2 role in nuclear-mitochondria communication, these findings reveal an exquisite regulatory network for modulating mitochondrial gene expression through spatially coordinated transcription and translation.

Summary: High-sensitivity nanoflow liquid chromatography (nLC) is seldom employed in untargeted metabolomics because current sample preparation techniques are inefficient at preventing nanocapillary column performance degradation. Here, we describe an nLC-based tandem mass spectrometry workflow that enables seamless joint analysis and integration of metabolomics (including lipidomics) and proteomics from the same samples without instrument duplication. This workflow is based on a robust solid-phase micro-extraction step for routine sample cleanup and bioactive molecule enrichment. Our method, termed proteomic and nanoflow metabolomic analysis (PANAMA), improves compound resolution and detection sensitivity without compromising the depth of coverage as compared with existing widely used analytical procedures. Notably, PANAMA can be applied to a broad array of specimens, including biofluids, cell lines, and tissue samples. It generates high-quality, information-rich metabolite-protein datasets while bypassing the need for specialized instrumentation. Motivation: The ability to routinely, sensitively, and reproducibly analyze both cellular proteins and metabolite mixtures from the same biospecimens can enhance the discovery of biomolecules associated with basic biochemical processes and pathobiological states. Yet existing mass spectrometry-based profiling methods rely on specialized protocols and duplicated instrumentation platforms, resulting in increased time, sample consumption, and costs. We sought to generate an effective platform for both metabolomics and proteomics studies on the same samples by enabling nanoflow liquid chromatography for small molecules. The resulting approach was extensively optimized and benchmarked to provide in-depth molecular coverage, along with improved chromatographic separation, sensitivity, and reliability as compared with existing methods. The cost-benefit ratio of PANAMA is substantial because the platform bypasses the need for specialized instrumentation stemming from incompatible procedures.

Objective To assess pathological characteristics, clinical features and outcomes of patients diagnosed with peripheral zone (PZ) and transition zone (TZ) prostate cancer after prostatectomy.Methods and analysis We systematically reviewed PubMed, EMBASE and MEDLINE. Primary endpoints were biochemical relapse-free survival (bRFS) and distant metastases rate; secondary endpoints included clinical and pathological features.Results Ten retrospective cohort studies were identified, six reported HRs for bRFS between PZ and TZ tumours. Patients with TZ tumours had significantly better bRFS (pooled HR 0.57 (0.47, 0.68)) than those with PZ tumours. Two studies reported a lower proportion of distant metastasis in patients diagnosed with TZ tumours compared with PZ tumours (1.5% vs 4.9% (median follow-up 7.0 years) and 0% vs 5% (median follow-up 7.8 years)). PZ tumours presented higher Gleason group and T staging more frequently, while TZ tumours were associated with higher prostate specific antigen levels at diagnosis.Conclusion PZ tumours were associated with poorer prognostic clinical features and outcomes. Despite adjusting for poor prognostic clinical features, PZ tumours consistently showed worse clinical outcomes than TZ tumours. Our systematic review underscores the need for further research comparing PZ and TZ prostate cancer to understand the underlying differences and refine clinical practice.

Control strategies for lower limb prostheses have made multiple significant advancements over the years. In this work, we investigate the scope and capabilities of a controller for ankle-foot prostheses that relies only on a one-degree-of-freedom inertial sensor, supplemented with a control algorithm that can perform a real time update of actuation parameters using gait information available from past gait cycles. The updated actuation parameters are applied to the subsequent gait cycle and the cycle repeats itself. The idea behind this controller is to allow a user to have infinite possible variations in gait speeds (within the allowable limits of actuation) while keeping the required sensory inputs to a minimum. As a consequence of this controller design, the user is not forced to choose discrete speeds of walking (slow, medium, fast) and is capable of freely varying his gait speeds on each step, while utilizing only a single-degree-of-freedom sensor. We implement the controller on an actuated transtibial prosthesis prototype based on a series-elastic spring configuration, and conduct tests for level ground walking at a self-selected walking speed, to explore the achievable range of response pertaining to daily living tasks. The pilot tests on a healthy participant, conducting level ground walking with turns and remotely controlling the prosthesis, suggest that it is possible to control a transtibial prosthesis using a simple uni-sensor framework, with a maximum angular deviation of 5°, and maximum deviation in angular velocity of $20^{\circ} /s$ compared to that of healthy humans.

BackgroundClinical decision support (CDS) tools that incorporate machine learning–derived content have the potential to transform clinical care by augmenting clinicians’ expertise. To realize this potential, such tools must be designed to fit the dynamic work systems of the clinicians who use them. We propose the use of academic detailing—personal visits to clinicians by an expert in a specific health IT tool—as a method for both ensuring the correct understanding of that tool and its evidence base and identifying factors influencing the tool’s implementation. ObjectiveThis study aimed to assess academic detailing as a method for simultaneously ensuring the correct understanding of an emergency department–based CDS tool to prevent future falls and identifying factors impacting clinicians’ use of the tool through an analysis of the resultant qualitative data. MethodsPreviously, our team designed a CDS tool to identify patients aged 65 years and older who are at the highest risk of future falls and prompt an interruptive alert to clinicians, suggesting the patient be referred to a mobility and falls clinic for an evidence-based preventative intervention. We conducted 10-minute academic detailing interviews (n=16) with resident emergency medicine physicians and advanced practice providers who had encountered our CDS tool in practice. We conducted an inductive, team-based content analysis to identify factors that influenced clinicians’ use of the CDS tool. ResultsThe following categories of factors that impacted clinicians’ use of the CDS were identified: (1) aspects of the CDS tool’s design (2) clinicians’ understanding (or misunderstanding) of the CDS or referral process, (3) the busy nature of the emergency department environment, (4) clinicians’ perceptions of the patient and their associated fall risk, and (5) the opacity of the referral process. Additionally, clinician education was done to address any misconceptions about the CDS tool or referral process, for example, demonstrating how simple it is to place a referral via the CDS and clarifying which clinic the referral goes to. ConclusionsOur study demonstrates the use of academic detailing for supporting the implementation of health information technologies, allowing us to identify factors that impacted clinicians’ use of the CDS while concurrently educating clinicians to ensure the correct understanding of the CDS tool and intervention. Thus, academic detailing can inform both real-time adjustments of a tool’s implementation, for example, refinement of the language used to introduce the tool, and larger scale redesign of the CDS tool to better fit the dynamic work environment of clinicians.

Sacroiliac (SI) joint dysfunction can lead to debilitating pain but can be treated with minimally invasive sacroiliac joint fusion (SIJF). This treatment is commonly performed using 2D fluoroscopic guidance. This makes placing the implants without damaging surrounding neural structures challenging. Virtual surgical planning (VSP) using simulated fluoroscopic images may improve intraoperative guidance. This article describes a workflow with VSP in SIJF using simulated fluoroscopic images and evaluates achieved implant placement accuracy. Ten interventions were performed on 10 patients by the same surgeon, resulting in a total of 30 implants; the median age was 39 years, and all patients were female. The overall mean implant placement accuracy was 4.9 ± 1.26 mm and 4.0 ± 1.44°. There were no malpositioning complications. VSP helped the surgeon understand the anatomy and determine the optimal position and length of the implants. The planned positions of the implants could be reproduced in surgery with what appears to be a clinically acceptable level of accuracy.

Background: The aim of this study was to identify items that healthcare providers and/or patients consider important to include in a questionnaire for clinical trials and cohort studies in shoulder instability research. This could serve as a basis to develop a core outcome set for shoulder instability research. Methods: Healthcare providers and patients were included in a panel for a modified Delphi consensus study. The study consisted of three rounds, comprising (1) identifying items, (2) rating the importance of the items, and (3) rating the importance again after seeing a summary of the results of round two. Importance was rated on a 9-point Likert scale. Consensus was defined as ≥ 80% of the panel giving a score of 7 or higher. Results: In total, 44 healthcare providers and 30 patients completed all three rounds. Round one identified 54 items. After round three, the panel reached a consensus on 11 items that should be included in a questionnaire, comprising re-dislocation (99%), instable feeling of the shoulder (96%), limitations during sport (93%), patient satisfaction with the shoulder (93%), fear/anxiety for re-dislocation (91%), range of motion (88%), return to old level of functioning (85%), performing daily activities (85%), return to sport (82%), return to work (82%), and trusting the shoulder (81%). Conclusion: Healthcare providers and patients reached a consensus on 11 items that should be included in a questionnaire for shoulder instability research. These items can facilitate design and development of future clinical trials and form the basis for the development of a core outcome set.

Audiovisual recordings of lectures are available to many students in all disciplines. The use of lecture recordings has been studied extensively, but it is still not clear how, or how much, they are actually used. Previous analysis of their use has been based on either survey data or computer logs of access. In the latter case, measurements of actual use have usually been based on counts of the number of times recordings have been accessed. This does not distinguish those that happen accidentally ('hits'), from those that might permit learning ('views'). This distinction is essential to the meaningful analysis of the log of the actual use of recorded lectures. Using the access logs of undergraduate science students, we show that the distribution of the durations of the access of recordings of scheduled lectures has two distinct components. The most rapid of these is complete within three minutes and we infer that it reflects the behaviour of students searching among recordings. This inference is based on a comparison of these distributions with those of (i) recordings made automatically during a non-teaching period and (ii) individual users. This is also consistent with the pattern of usage by students searching for a specific recording.

Humble leaders are traditionally thought to create a great deal of human and social capital, yet be overshadowed by self‐promoting rivals for promotions. We propose that through informal career mentoring, humble leaders can improve their organizational status and promotability. We tested our model among a multisource sample of 610 leaders across 18 industries and 21 job functions who participated in a leader development program. Leader humility was reported by the focal leaders' peers, leader mentoring behavior was reported by the focal leaders' direct reports, leader status was reported by the focal leaders' immediate bosses, and leader promotability was reported by the focal leaders' superiors. Results generally confirmed that leader humility predicted leader mentoring behavior, which in turn predicted leader status, and ultimately higher leader promotability ratings. We discuss how our findings extend and enrich the literatures on leader humility and mentoring, showing how humble leaders can ascend organizational hierarchies. [ABSTRACT FROM AUTHOR]

There is a growing number of personal healthcare devices that are in prolonged contact with the skin. The functionality of these products is linked to the interface formed by the contact between the medical apparatus and the skin. The interface can be characterised by its topology, compliance, and moisture and thermal regulating capabilities. Many devices are, however, described to have suboptimal and occlusive contacts, resulting in physiological unfavourable microclimates at the interface. The resulting poor management of moisture and temperature can impact the functionality and utility of the device and, in severe cases, lead to physical harm to the user. Being able to control the microclimate is therefore expected to limit medical-device related injuries and prevent associated skin complications. Surface engineering can modify and potentially enhance the regulation of the microclimate factors surrounding the interface between a product's surface and the skin. This review provides an overview of potential engineering solutions considering the needs for, and influences on, regulation of temperature and moisture by considering the skin-medical device interface as a system. These findings serve as a platform for the anticipated progress in the role of surface engineering for skin-device microclimate regulation.

Introduction: Sacroiliac joint fusion (SIJF) is a minimally invasive treatment for sacroiliac (SI) dysfunction. It involves placing implants through the SI joint under fluoroscopic guidance, requiring precise implant positioning to avoid nerve injury. Preoperative virtual surgical planning (VSP) aids in optimal positioning, but replicating it accurately in the operating room is challenging. Research question: This study aims to assess the feasibility of superimposing VSP onto intraoperative fluoroscopic images to aid in optimal implant placement. Material and methods: A method for intraoperative guidance using 3D/2D registration was developed and tested during SIJF as an available and potentially efficient alternative for costly and more invasive navigation systems. Preoperatively, a VSP is performed and simulated fluoroscopic images are generated from a preoperative CT scan. During surgery, the simulated image that visually best matches the intraoperative fluoroscopic image is selected. Subsequently, the VSP is superimposed onto the intraoperative fluoroscopic image using a developed script-based workflow. The surgeon then places the implants accordingly. Postoperative implant placement accuracy was evaluated. Results: Five interventions were performed on five patients, resulting in a total of 15 placed implants. Minor complications without clinical consequences occurred in one case, primarily attributable to the patient's anatomy and pathological manifestations. Mean deviations at implant apex and 3D angle were 4.7 ± 1.6 mm and 3.5 ± 1.3°, respectively. Discussion and conclusions: The developed intraoperative workflow was feasible and resulted in implants placed with low deviations from the VSP. Further research is needed to automate and validate this method in a larger cohort.

Background: Induced pluripotent stem cells (iPSCs) directed to endothelial identity (iPSC-ECs) are emerging as a potent tool for regenerative medicine in vascular disease. However, iPSC-ECs lose expression of key identity markers under standard in vitro conditions, limiting their clinical applications. Methods: To model physiological in vivo conditions, we examined the bioenergetics, presence of key cell markers, and proliferative and angiogenic capacity in iPSC-ECs at late and early passage under hyperoxic (21%) and physiological (4%) oxygen concentrations. Results: Physoxia resulted in relative preservation of mitochondrial bioenergetic activity, as well as CD144 expression in late passage iPSC-ECs, but not proliferative capacity or tube formation. Single cell RNA sequencing (scRNA-seq) revealed that late passage hyperoxic iPSC-ECs develop an endothelial-to-mesenchymal phenotype. Comparing scRNA-seq data from iPSC-ECs and from atherosclerotic ECs revealed overlap of their transcriptional phenotypes. Conclusions: Taken together, our studies demonstrate that physiological 4% oxygen culture conditions were sufficient to improve mitochondrial function in high passage cells, but alone was insufficient to preserve angiogenic capacity. Furthermore, late passage cells under typical conditions take on an endothelial-to-mesenchymal phenotype with similarities to ECs found in atherosclerosis.

Objective: The purpose of this study was to examine system- and patient-level factors associated with the number of healthcare disciplines involved in delivery of patient education among hospitalized older cancer survivors. Methods: We used electronic health record (EHR) data from a single institution documenting patient education among hospitalized older patients (≥65 years) with a history of cancer between 9/1/2018 and 10/1/2019. We used parametric ordinal logistic regression to assess the number of healthcare disciplines involved in documented education activities. Results: The sample (n = 446) was predominantly male, White, and on average 74 years old. Adjusting for patient and system-level variables, men and larger department units had higher odds of receiving education from fewer healthcare disciplines. Patients with a history of breast or prostate cancer and longer lenths of stay had lower odds of receiving patient education from fewer healthcare disciplines. Conclusion: Hospital size, severity of illness, and cancer type are associated with delivery of multidisciplinary education in this sample. Innovation: EHR provides an opportunity to identify patterns in patient education among cancer survivors. Future research should investigate provider perspectives of the findings to inform provider- and system-level strategies to improve patient education.

Peripheral arterial disease (PAD) is an age-related medical condition affecting mostly muscular arteries of the limb. It is the 3rd leading cause of atherosclerotic morbidity. The mechanical environment of endothelial cells (ECs) in PAD is characterized by disturbed blood flow (d-flow) and stiff extracellular matrices. In PAD, the stiffness of arteries is due to decreased elastin function and increased collagen content. These flow and stiffness parameters are largely missing from current models of PAD. It has been previously proven that ECs exposed to d-flow or stiff substrates lead to proatherogenic pathways, but the effect of both, d-flow and stiffness, on EC phenotype has not been fully investigated. In this study, we sought to explore the effect of sex on proatherogenic pathways that could result from exposing endothelial cells to a d-flow and stiff environment. We utilized the scRNA-seq tool to analyze the gene expression of ECs exposed to the different mechanical conditions both in vitro and in vivo. We found that male ECs exposed to different mechanical stimuli presented higher expression of genes related to fibrosis and d-flow in vitro. We validated our findings in vivo by exposing murine carotid arteries to d-flow via partial carotid artery ligation. Since women have delayed onset of arterial stiffening and subsequent PAD, this work may provide a framework for some of the pathways in which biological sex interacts with sex-based differences in PAD.

In this paper we presented the mechanical design and evaluation of a low-profile and lightweight exoskeleton that supports the finger extension of stroke patients during daily activities without applying axial forces to the finger. The exoskeleton consists of a flexible structure that is secured to the index finger of the user while the thumb is fixed in an opposed position. Pulling on a cable will extend the flexed index finger joint such that objects can be grasped. The device can achieve a grasp size of at least 7 cm. Technical tests confirmed that the exoskeleton was able to counteract the passive flexion moments corresponding to the index finger of a severely affected stroke patient (with an MCP joint stiffness of k = 0.63Nm/rad), requiring a maximum cable activation force of 58.8N. A feasibility study with stroke patients (n=4) revealed that the body-powered operation of the exoskeleton with the contralateral hand caused a mean increase of 46° in the range of motion of the index finger MCP joint. The patients (n=2) who performed the Box & Block Test were able to grasp and transfer maximally 6 blocks in 60 sec. with exoskeleton, compared to 0 blocks without exoskeleton. Our results showed that the developed exoskeleton has the potential to partially restore hand function of stroke patients with impaired finger extension capabilities. An actuation strategy that does not involve the contralateral hand should be implemented during further development to make the exoskeleton suitable for bimanual daily activities.

Introduction: Emergency medicine (EM) residency programs have variable approaches to educating residents on recognizing and managing healthcare disparities. We hypothesized that our curriculum with resident-presented lectures would increase residents’ sense of cultural humility and ability to identify vulnerable populations. Methods: At a single-site, four-year EM residency program with 16 residents per year, we designed a curriculum intervention from 2019–2021 where all second-year residents selected one healthcare disparity topic and gave a 15-minute presentation overviewing the disparity, describing local resources, and facilitating a group discussion. We conducted a prospective observational study to assess the impact of the curriculum by electronically surveying all current residents before and after the curriculum intervention. We measured attitudes on cultural humility and ability to identify healthcare disparities among a variety of patient characteristics (race, gender, weight, insurance, sexual orientation, language, ability, etc). Statistical comparisons of mean responses were calculated using the Mann-Whitney U test for ordinal data. Results: A total of 32 residents gave presentations that covered a broad range of vulnerable patient populations including those that identify as Black, migrant farm workers, transgender, and deaf. The overall survey response was 38/64 (59.4%) pre-intervention and 43/64 (67.2%) post-intervention. Improvements were seen in resident self-reported cultural humility as measured by their responsibility to learn (mean responses of 4.73 vs 4.17; P < 0.001) and responsibility to be aware of different cultures (mean responses of 4.89 vs 4.42; P < 0.001). Residents reported an increased awareness that patients are treated differently in the healthcare system based on their race ( P < 0.001) and gender ( P < 0.001). All other domains queried, although not statistically significant, demonstrated a similar trend. Conclusion: This study demonstrates increased resident willingness to engage in cultural humility and the feasibility of resident near-peer teaching on a breadth of vulnerable patient populations seen in their clinical environment. Future studies may query the impact this curriculum has on resident clinical decision-making.

Objectives: There is a concern that provide increased extraneous cognitive load when paired with residents on shift. However, this may be offset by the decrease in extraneous load they may provide to the residents they are paired with by offloading basic patient care tasks. We hypothesized that these forces may not be balanced. Methods: We conducted a retrospective observational analysis of PGY‐2 emergency medicine residents and junior medical students at a single academic emergency department (ED) in the Midwest. A series of efficiency metrics (relative value unit [RVUs], patients per hour [PPH], time to note completion, and resident assignment to disposition [RATD]) as well as one quality metric (number of return ED visits; "bouncebacks") were compared for resident shifts in which a student was paired with the resident as well those in which no student was paired utilizing a regression model. Results: A total of 1844 records met the inclusion criteria (214 shifts with a paired medical student and 1630 without). After covariates were adjusted for, medical student shift status was a statistically significant predictor of increases in PPH (p < 0.0001) and RVUs (p = 0.0161) but was not significantly associated with RATD (p = 0.6941), log‐time to note completion (p = 0.1604), or bounceback status (p = 0.9840). Shifts where residents were paired with medical students were predicted to see an additional 1.131 (95% confidence interval [CI] 0.660–1.602) PPH and produce an additional 1.923 RVUs (95% CI 1.130–3.273) per shift relative to shifts without medical students. Conclusions: When junior medical students were paired with a PGY‐2 resident on ED shifts, there was a significant increase in the PPH and RVUs generated when compared with shifts in which no medical student was paired with them. [ABSTRACT FROM AUTHOR]

The daily usage of a prosthesis for people with an amputation consists of phases of intermittent and continuous walking patterns. Based on this observation, this paper introduces a novel hybrid architecture to control a transfemoral prosthesis, where separate algorithms are used depending on these two different types of movement. For intermittent walking, an interpolation-based algorithm generates control signals for the ankle and knee joints, whereas, for continuous walking, the control signals are generated utilizing an adaptive frequency oscillator. A switching strategy that allows for smooth transitioning from one controller to another is also presented in the design of the architecture. The individual algorithms for the generation of the joints angles’ references, along with the switching strategy were experimentally validated on a pilot test with a healthy subject wearing an able-bodied adapter and a designed transfemoral prosthesis. The results demonstrate the capability of the individual algorithms to generate the required control signals while undergoing smooth transitions when required. Through the use of a combination of interpolation and adaptive frequency oscillator-based methods, the controller also demonstrates its response adaptation capability to various walking speeds.

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has been approved by the Food and Drug Administration (FDA) to identify prostate cancer in the setting of biochemical recurrence but can also identify other malignancies. 18F-PSMA PET has not been studied as a potential tool for hepatocellular carcinoma (HCC). We describe the case of a 76-year-old male with a rising prostate-specific antigen (PSA) after definitive prostate cancer treatment and no prior liver pathology who was incidentally found to have HCC on 18F-PSMA PET.

Introduction: Emergency medicine (EM) residents take the American Board of Emergency Medicine (ABEM) In-Training Examination (ITE) every year. This examination is based on the ABEM Model of Clinical Practice (Model). The purpose of this study was to determine whether a relationship exists between the number of patient encounters a resident sees within a specific clinical domain and their ITE performance on questions that are related to that domain. Methods: Chief complaint data for each patient encounter was taken from the electronic health record for EM residents graduating in three consecutive years between 2016–2021. We excluded patient encounters without an assigned resident or a listed chief complaint. Chief complaints were then categorized into one of 20 domains based on the 2016 Model. We calculated correlations between the total number of encounters seen by a resident for all clinical years and their ITE performance for the corresponding clinical domain from their third year of training. Results: Available for analysis were a total of 232,625 patient encounters and 69 eligible residents who treated the patients. We found no statistically significant correlations following Bonferroni correction for multiple analyses. Conclusion: There was no correlation between the number of patient encounters a resident has within a clinical domain and their ITE performance on questions corresponding to that domain. This suggests the need for separate but parallel educational missions to achieve success in both the clinical environment and standardized testing.

Abstract Most strategies to treat obesity-related disorders have involved prevention of diet-induced weight gain in lean mice. Treatment of obese individuals will require therapies that reverse the detrimental effects of excess body weight. Cyclin-dependent kinases have been shown to contribute to obesity and its adverse complications. Here, we show that roscovitine; a an orally available cyclin-dependent kinase inhibitor; given to male mice during the last six weeks of a 19-week high fat diet, reduced weight gain and prevented accompanying insulin resistance, hepatic steatosis, visceral adipose tissue (eWAT) inflammation/fibrosis as well as restored insulin secretion and enhanced whole body energy expenditure. Proteomics and phosphoproteomics analysis of eWAT demonstrated that roscovitine suppressed expression of peptides and phosphopeptides linked to inflammation and extracellular matrix proteins. It also identified 17 putative protein kinases perturbed by roscovitine, including CMGC kinases, AGC kinases and CAMK kinases. Pathway enrichment analysis showed that lipid metabolism, TCA cycle, fatty acid beta oxidation and creatine biosynthesis are enriched following roscovitine treatment. For brown adipose tissue (BAT), analysis of upstream kinases controlling the phosphoproteome revealed two major kinase groups, AGC and CMGC kinases. Among the top enriched pathways were insulin signaling, regulation of lipolysis in adipocytes, thyroid hormone signaling, thermogenesis and cAMP-PKG signaling. We conclude that roscovitine is effective at preventing prolonged diet-induced metabolic disruption and restoring mitochondrial activity in BAT and eWAT.