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Aims The 6-min-walk test (6MWT) is a validated proxy for frailty and a predictor of clinical outcomes, yet is not widely used due to implementation challenges. This comparative effectiveness study assesses the reliability and repeatability of a home-based 6MWT compared to in-clinic 6MWTs in patients with cardiovascular disease. Methods and results One hundred and ten (110) patients scheduled for cardiac or vascular surgery were enrolled during a study period from June 2018 to December 2019 at the Palo Alto VA Hospital. Subjects were provided with an Apple iPhone 7 and Apple Watch Series 3 loaded with the VascTrac research study application and performed a supervised in-clinic 6MWT during enrolment, at 2 weeks, 1, 3, and 6 months post-operatively. Subjects also received notifications to perform at-home smartphone-based 6MWTs once a week for a duration of 6 months. Test–retest reliability of in-clinic measurements and at-home measurements was assessed with an industry standard Cronbach’s alpha reliability test. Test–retest reliability for in-clinic ground truth 6MWT steps vs. in-clinic iPhone 6MWT steps was 0·99, showing high reliability between the two tested measurements. When comparing for in-clinic ground truth 6MWT steps vs. neighbouring at-home iPhone 6MWT steps, reliability was 0·74. Conclusion Running the test–reliability test on both measurements shows that an iPhone 6MWT test is reliable compared to an in-clinic ground truth measurement in patients with cardiovascular disease.

O-GlcNAc modification plays important roles in metabolic regulation of cellular status. Two homologs of O-GlcNAc transferase, SECRET AGENT (SEC) and SPINDLY (SPY), which have O-GlcNAc and O-fucosyl transferase activities, respectively, are essential in Arabidopsis but have largely unknown cellular targets. Here we show that AtACINUS is O-GlcNAcylated and O-fucosylated and mediates regulation of transcription, alternative splicing (AS), and developmental transitions. Knocking-out both AtACINUS and its distant paralog AtPININ causes severe growth defects including dwarfism, delayed seed germination and flowering, and abscisic acid (ABA) hypersensitivity. Transcriptomic and protein-DNA/RNA interaction analyses demonstrate that AtACINUS represses transcription of the flowering repressor FLC and mediates AS of ABH1 and HAB1, two negative regulators of ABA signaling. Proteomic analyses show AtACINUS’s O-GlcNAcylation, O-fucosylation, and association with splicing factors, chromatin remodelers, and transcriptional regulators. Some AtACINUS/AtPININ-dependent AS events are altered in the sec and spy mutants, demonstrating a function of O-glycosylation in regulating alternative RNA splicing., AtACINUS is an Arabidopsis homolog of a mammalian splicing regulator and previously found to be O-GlcNAcyated. Here Bi et al. characterize the interactors and targets of AtACINUS, show it is required for development and stress responses and provide evidence that its O-glycosylation affects alternative splicing.

Background Supervised exercise therapy (SET) is an inexpensive, low-risk, and effective option when compared with invasive therapies for the treatment of patients with peripheral artery disease (PAD) and intermittent claudication. Randomized, controlled trials have demonstrated the benefits of SET in improving maximum walking distance in intermittent claudication patients, and society guidelines recommend SET as first-line therapy. In 2017, the Centers for Medicare & Medicaid Services (CMS) added coverage of SET. We aimed to evaluate the availability and use of SET programs, determine the awareness of SET CMS coverage in the United States, and gauge the academic interest in SET in the vascular community. Methods An eight-question online survey regarding SET coverage, reimbursement, barriers to prescription, and SET use was sent to 900 vascular surgeons, cardiologists, and vascular medicine physicians across the United States. The most recent 2-year programs for the Vascular Annual Meeting, Midwestern Vascular Society, Eastern Vascular Society, and Western Vascular Society were reviewed to identify SET-related abstracts and gauge academic interest and awareness for SET within the vascular surgery community. Results We received 135 physician responses (15%) to the survey. All 50 states were represented. The majority of responders (54%) stated that there was no SET program at their facility, and 5% did not know if there was a SET program available. Of those who did have a SET program available, 81% were associated with cardiac rehabilitation and 19% had a PAD-specific program. A significant number of physicians (49%) had never referred a patient for SET. Twenty-six percent were not aware that CMS covered SET sessions. Of the physicians who were aware of CMS reimbursement, 36% had never referred a patient to a SET program. Of all surveyed, 98% indicated they would refer patients to a SET program if one was available. Top barriers to use of a SET program included (1) no SET center availability and (2) significant cost or travel expense to the patient. A review of major vascular surgery meeting programs for the last 2 years yielded no identification of a SET-related abstract. Conclusions There is a lack of both availability and use of SET for patients with PAD with claudication, despite guideline recommendations and CMS reimbursement for SET sessions in the United States. When SET is offered, it is typically through cardiac rehabilitation programs which is not focused on PAD. Travel distance, lack of SET program availability, and low reimbursement rates are primary areas that could be addressed to improve use.

Clinical practice guidelines recommend supervised exercise therapy (SET) as first-line therapy for patients with peripheral artery disease (PAD) and intermittent claudication (IC). The Society for Vascular Surgery Appropriate Use Criteria for IC deems excercise therapy (ET) as appropriate for all patients with IC. However, compliance with recommendations for the use of ET is often poor owing to the lack of availability, patient travel requirements, and cost. Results of home-based ET programs have been mixed with a trend toward improved results with more frequent patient engagement. The feasibility, use, and effectiveness of a 12-week app-based structured ET program using cognitive-behavioral therapy (CBT) techniques for IC was evaluated.Patients with PAD confirmed by an abnormal ankle-brachial index or toe-brachial index and IC were recruited prospectively to participate in Society for Vascular Surgery SET, a 12-week app-based ET program. Participants performed home 6-minute walk tests, completed quality-of-life surveys, received education options via micro learning courses (eg, What is PAD?, Exercise, and Nutrition), and ongoing health coaching using CBT techniques. They were instructed to record at least three 30-minute ET walks a week using their personal mobile phones. Programming also included daily doses of health education, coaching, and reminders sent via text message.One hundred thirty-nine patients (37% women; mean age, 65 years) were enrolled across 20 institutions (44% offered in-person ET programs). One hundred twenty patients (86%) completed the program. Participants recorded 201,163 minutes of walking 8,013,520 steps with the ET program, completing a total of 5049 SET walks. Nineteen enrolled participants (14%) became inactive because they either paused (14 participants: medical reasons, travel, or other) or withdrew (5 participants: security concerns, lack of motivation). Ninety-two percent of patients met their stated CBT specific, measurable, achievable, relevant, and time-bound goals. Freedom from intervention at 6 months was 92% and 69% at 12 months.Deployment of a 12-week app-based ET program for PAD incorporating CBT was feasible in achieving 86% program completion and effective at meeting guideline recommended activity goals. Ninety-two percent of participants achieved their CBT specific, measurable, achievable, relevant, and time-bound goals. The use of ET was increased by virtue of offering this program at institutions that did not offer ET.

O-GlcNAc modification plays important roles in metabolic regulation of cellular status. Two homologs of O-GlcNAc transferase, SECRET AGENT (SEC) and SPINDLY (SPY), which have O-GlcNAc and O-fucosyl transferase activities, respectively, are essential inArabidopsisbut have largely unknown cellular targets. Here we show that AtACINUS is O-GlcNAcylated and O-fucosylated and mediates regulation of transcription, alternative splicing (AS), and developmental transitions. Knocking-out both AtACINUS and its distant paralog AtPININ causes severe growth defects including dwarfism, delayed seed germination and flowering, and abscisic acid (ABA) hypersensitivity. Transcriptomic and protein-DNA/RNA interaction analyses demonstrate that AtACINUS represses transcription of the flowering repressorFLCand mediates AS ofABH1andHAB1, two negative regulators of ABA signaling. Proteomic analyses show AtACINUS’s O-GlcNAcylation, O-fucosylation, and association with splicing factors, chromatin remodelers, and transcriptional regulators. Some AtACINUS/AtPININ-dependent AS events are altered in thesecandspymutants, demonstrating a function of O-glycosylation in regulating alternative RNA splicing.

Objectives Densitometry on paired inspiratory and expiratory multidetector computed tomography (MDCT) for the quantification of air trapping is an important approach to assess functional changes in airways diseases such as cystic fibrosis (CF). For a regional analysis of functional deficits, an accurate lobe segmentation algorithm applicable to inspiratory and expiratory scans is beneficial. Materials and methods We developed a fully automated lobe segmentation algorithm, and subsequently validated automatically generated lobe masks (ALM) against manually corrected lobe masks (MLM). Paired inspiratory and expiratory CTs from 16 children with CF (mean age 11.1±2.4) acquired at 4 time-points (baseline, 3mon, 12mon, 24mon) with 2 kernels (B30f, B60f) were segmented, resulting in 256 ALM. After manual correction spatial overlap (Dice index) and mean differences in lung volume and air trapping were calculated for ALM vs. MLM. Results The mean overlap calculated with Dice index between ALM and MLM was 0.98±0.02 on inspiratory, and 0.86±0.07 on expiratory CT. If 6 lobes were segmented (lingula treated as separate lobe), the mean overlap was 0.97±0.02 on inspiratory, and 0.83±0.08 on expiratory CT. The mean differences in lobar volumes calculated in accordance with the approach of Bland and Altman were generally low, ranging on inspiratory CT from 5.7±52.23cm3 for the right upper lobe to 17.41±14.92cm3 for the right lower lobe. Higher differences were noted on expiratory CT. The mean differences for air trapping were even lower, ranging from 0±0.01 for the right upper lobe to 0.03±0.03 for the left lower lobe. Conclusions Automatic lobe segmentation delivers excellent results for inspiratory and good results for expiratory CT. It may become an important component for lobe-based quantification of functional deficits in cystic fibrosis lung disease, reducing necessity for user-interaction in CT post-processing.

Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. However, the proteins and sites subject to this posttranslational modification are largely unknown. Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level.