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In the care of type 1 diabetes, there is growing adoption of hybrid closed loop systems, as they have been shown in clinical trials and real-world use to safely provide favorable glycemic control compared to multiple daily injection and compared to sensor augmented pump therapies1-3. However, access to these technologies is often limited, as a stepwise approach to diabetes technologies is recommended. Hence, people with diabetes requiring intensive insulin therapy must start with multiple daily injection (MDI) therapy and self-monitoring blood glucose (SMBG) or intermittent scanning continuous glucose monitoring (CGM) before progressing to MDI therapy with real-time CGM, eventually moving on to automated insulin delivery (AID) system therapy if necessary4. This can be a lengthy process, exposing people with diabetes to prolonged periods of suboptimal blood glucose levels. Following this stepwise approach, there is evidence to support an improvement in glucose control with the MiniMedTM 780G Advanced Hybrid Closed Loop AID system compared to its predecessors (MiniMedTM 670G system)5 and to sensor-augmented pumps with predictive low glucose management6. However, to support a more direct approach to advanced diabetes management technology, it was of interest to compare the MiniMedTM 780G system to the most prevalent therapy, namely multiple daily injections (MDI) with intermittent scanning continuous glucose monitoring (isCGM)7.

Background: Mitochondria play vital roles in cellular function and homeostasis. Inhalation of aerosols generated by E-cigarettes (E-Cig) may affect mitochondrial physiology. Data on risks of E-Cigs and vaping devices on mitochondria physiology remain incomplete. Our objective was to investigate novel effects of E-Cig plasma mediators on mitochondrial physiology in human endothelial (EA.hy 926) and lung epithelial cells (A549). Hypothesis: Plasma from E-Cig users will induce alterations in mitochondrial physiology. Methods: A longitudinal cohort study was conducted on subjects who used E-cigarettes (n=21) and 10 non-smoking, non-vaping controls. Inclusion criteria were active E-Cig use without known lung disease and with normal lung function, between the ages of 18-30 years. E-Cig use was confirmed with in-person interviews and plasma cotinine levels. Active E-Cig use was defined as use of >0.5-1 mL e-liquid/day or 3.5-7 mL/week for >6 months. Plasma was isolated and stored at -70°C. The metabolic stress effects of E-Cig plasma (1%, 1h conditioning) mediators were assessed in vitro on endothelial cells (8x104/well) and epithelial cells (5x104/well) using the Seahorse XF Energy phenotype Test. The mitochondrial copy number in E-Cig user plasma was estimated by digital droplet PCR. Membrane potentials and reactive oxygen species (ROS) were quantified by Cytation5. Results: E-Cig plasma altered the metabolic stress phenotype of mitochondria of EA.hy 926 and A549 cells. Metabolic stress was evidenced by increased oxygen consumption and glycolytic rates in both cell types. The mitochondria membrane potential and ROS levels significantly increased in E-Cig plasma subjected cells. Mitochondrial gene copy number levels were significantly increased in E-Cig user plasma suggesting mitochondrial stress in vivo. Conclusions: Plasma of E-cig users enhances maximal metabolic stress on human endothelial and lung cells in vitro and shows evidence for mitochondrial stress in vivo. These results may have important implications regarding the effects of E-Cig use on mitochondrial function and eventual public health recommendations. T31IP1929 and R21 AG058174-01A1 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Supplemental material, sj-docx-1-dst-10.1177_19322968231161320 for Advanced Hybrid Closed Loop in Adult Population With Type 1 Diabetes: A Substudy From the ADAPT Randomized Controlled Trial in Users of Real-Time Continuous Glucose Monitoring by Tim van den Heuvel, Ralf Kolassa, Winfried Keuthage, Jens Kroeger, Roseline Ré, Simona de Portu, Linda Vorrink, John Shin, Javier Castañeda, Robert Vigersky and Ohad Cohen in Journal of Diabetes Science and Technology

Batch effects (BEs) refer to systematic technical differences in data collection unrelated to biological variations whose noise is shown to negatively impact machine learning (ML) model generalizability. Here we release CohortFinder, an open-source tool aimed at mitigating BEs via data-driven cohort partitioning. We demonstrate CohortFinder improves ML model performance in downstream medical image processing tasks. CohortFinder is freely available for download at cohortfinder.com., Comment: 26 pages, 9 figures, 4 tables. Abstract was accepted by European Society of Digital and Integrative Pathology (ESDIP), Germany, 2022

Supplemental Material for Utilization of Machine Learning to Model Important Features of 30-day Readmissions following Surgery for Metastatic Spinal Column Tumors: The Influence of Frailty by Bogdan G. Popescu and Mircea Popa in Global Spine Journal

Supplemental Material, sj-docx-1-gsj-10.1177_21925682211022290 for Racial Disparities in Perioperative Morbidity Following Oncological Spine Surgery by Rafael De la Garza Ramos, Jong Hyun Choi, Ishan Naidu, Joshua A. Benton, Murray Echt, Vijay Yanamadala, Peter G. Passias, John H. Shin, David J. Altschul, C. Rory Goodwin, Daniel M. Sciubba and Reza Yassari in Global Spine Journal

INTRODUCTION As of May 04, 2020, the COVID-19 pandemic has affected over 3.5 million people and touched every inhabited continent. Accordingly, it has stressed health systems the world over leading to the cancellation of elective surgical cases and discussions regarding healthcare resource rationing. It is expected that rationing of surgical resources will continue even after the pandemic peak, and may recur with future pandemics, creating a need for a means of triaging emergent and elective spine surgery patients. METHODS Using a modified Delphi technique, a cohort of 16 fellowship-trained spine surgeons from 10 academic medical centers constructed a scoring system for the triage and prioritization of emergent and elective spine surgeries. Three separate rounds of videoconferencing and written correspondence were used to reach a final scoring system. Sixteen test cases were used to optimize the scoring system so that it could categorize cases as requiring emergent, urgent, high-priority elective, or low-priority elective scheduling. RESULTS The devised scoring system included 8 independent components: neurological status, underlying spine stability, presentation of a highrisk post-operative complication, patient medical comorbidities, expected hospital course, expected discharge disposition, facility resource limitations, and local disease burden. The resultant calculator was deployed as a freely-available web-based calculator: https://jhuspine3.shinyapps.io/SpineUrgencyCalculator/ CONCLUSION Here we present the first quantitative urgency scoring system for the triage and prioritizing of spine surgery cases in resource-limited settings. We believe that our scoring system, while not all-encompassing, has potential value as a guide for triaging spine surgical cases during the COVID pandemic and post-COVID period.

Modern high-resolution microscopes, such as the scanning tunneling microscope, are commonly used to study specimens that have dense and aperiodic spatial structure. Extracting meaningful information from images obtained from such microscopes remains a formidable challenge. Fourier analysis is commonly used to analyze the underlying structure of fundamental motifs present in an image. However, the Fourier transform fundamentally suffers from severe phase noise when applied to aperiodic images. Here, we report the development of a new algorithm based on nonconvex optimization, applicable to any microscopy modality, that directly uncovers the fundamental motifs present in a real-space image. Apart from being quantitatively superior to traditional Fourier analysis, we show that this novel algorithm also uncovers phase sensitive information about the underlying motif structure. We demonstrate its usefulness by studying scanning tunneling microscopy images of a Co-doped iron arsenide superconductor and prove that the application of the algorithm allows for the complete recovery of quasiparticle interference in this material. Our phase sensitive quasiparticle interference imaging results indicate that the pairing symmetry in optimally doped NaFeAs is consistent with a sign-changing s+- order parameter.

Aims: Cognitive decline disproportionately affects older adult type 2 diabetes. We tested whether randomized intensive glucose-lowering reduces the rate(s) of cognitive decline in adults with advanced type 2 diabetes (mean: age, 60 years; diabetes duration, 11 years) from the Veterans Affairs Diabetes Trial. Methods: A battery of neuropsychological tests (digit span, digit symbol substitution (DSym), and Trails-making Part B (TMT-B)) was administered at baseline in ~1700 participants and repeated at year 5. Thirty-six risk factors were evaluated as predictors of cognitive decline in multivariable regression analyses.Results: The mean age-adjusted, DSym or TMT-B declined significantly in all study participants (P < 0.001). Randomized intensive glucose-lowering did not significantly alter the rate of cognitive decline. The final model of risk factors associated with 5-year decline in age-adjusted TMT-B included as significant predictors: longer baseline diabetes duration (beta = -0.028; P = 0.0057), lower baseline diastolic blood pressure (beta = 0.028; P < 0.001), and baseline calcium channel blocker medication use (beta = -0.639; P < 0.001). Higher baseline pulse pressure was significantly associated with decline in age-adjusted TMT-B suggesting a role for both higher systolic and lower diastolic blood pressure. Baseline thiazide diuretic use (beta= -0.549; P =0.015) was an additional significant predictor of 5-year decline in age-adjusted digit symbol score. Post-baseline systolic blood pressure-lowering was significantly associated (P < 0.001) with decline in TMT-B performance. There was a significant inverse association between post-baseline plasma triglyceride- lowering (P = 0.045) and decline in digit symbol substitution task performance.Conclusions: A five-year period of randomized intensive glucose-lowering did not significantly reduce the rate of cognitive decline in older-aged adults with type 2 diabetes. Systolic and diastolic blood pressure as well as plasma triglycerides were modifiable risk factors of the rate of cognitive decline in older adult type 2 diabetes.

OBJECTIVE: To evaluate a sensor-augmented insulin pump with a low glucose suspend (LGS) feature that automatically suspends basal insulin delivery for up to 2 h in response to sensor-detected hypoglycemia. RESEARCH DESIGN AND METHODS: The LGS feature of the Paradigm Veo insulin pump (Medtronic, Inc., Northridge, CA) was tested for 3 weeks in 31 adults with type 1 diabetes. RESULTS: There were 166 episodes of LGS: 66% of daytime LGS episodes were terminated within 10 min, and 20 episodes lasted the maximum 2 h. LGS use was associated with reduced nocturnal duration ≤2.2 mmol/L in those in the highest quartile of nocturnal hypoglycemia at baseline (median 46.2 vs. 1.8 min/day, P = 0.02 [LGS-OFF vs. LGS-ON]). Median sensor glucose was 3.9 mmol/L after 2-h LGS and 8.2 mmol/L at 2 h after basal restart. CONCLUSIONS: Use of an insulin pump with LGS was associated with reduced nocturnal hypoglycemia in those at greatest risk and was well accepted by patients.

Intracellular traffic between compartments of the secretory and endocytic pathways is mediated by vesicle-based carriers. The proteomes of carriers destined for many organelles are ill-defined because the vesicular intermediates are transient, low-abundance and difficult to purify. Here, we combine vesicle relocalisation with organelle proteomics and Bayesian analysis to define the content of different endosome-derived vesicles destined for the trans-Golgi network (TGN). The golgin coiled-coil proteins golgin-97 and GCC88, shown previously to capture endosome-derived vesicles at the TGN, were individually relocalised to mitochondria and the content of the subsequently re-routed vesicles was determined by organelle proteomics. Our findings reveal 45 integral and 51 peripheral membrane proteins re-routed by golgin-97, evidence for a distinct class of vesicles shared by golgin-97 and GCC88, and various cargoes specific to individual golgins. These results illustrate a general strategy for analysing intracellular sub-proteomes by combining acute cellular re-wiring with high-resolution spatial proteomics., The vesicles that transport proteins between intracellular organelles are small, short-lived, and elusive. Here, the authors show that capture of these vesicles through relocalizing tethers to mitochondria allows their contents to be characterised by organelle proteomics.