Decoding kinematic information from beta-band motor rhythms of speech motor cortex: a methodological/analytic approach using concurrent speech movement tracking and magnetoencephalography.

Introduction: Articulography and functional neuroimaging are two major tools for studying the neurobiology of speech production. Until now, however, it has generally not been feasible to use both in the same experimental setup because of technical incompatibilities between the two methodologies. Methods: Here we describe results from a novel articulography system dubbed Magneto-articulography for the Assessment of Speech Kinematics (MASK), which is technically compatible with magnetoencephalography (MEG) brain scanning systems. In the present paper we describe our methodological and analytic approach for extracting brain motor activities related to key kinematic and coordination event parameters derived from time-registered MASK tracking measurements. Data were collected from 10 healthy adults with tracking coils on the tongue, lips, and jaw. Analyses targeted the gestural landmarks of reiterated utterances/ipa/ and /api/, produced at normal and faster rates. Results: The results show that (1) Speech sensorimotor cortex can be reliably located in peri-rolandic regions of the left hemisphere; (2) mu (8-12 Hz) and beta band (13-30 Hz) neuromotor oscillations are present in the speech signals and contain information structures that are independent of those present in higher-frequency bands; and (3) hypotheses concerning the information content of speech motor rhythms can be systematically evaluated with multivariate pattern analytic techniques. Discussion: These results show that MASK provides the capability, for deriving subject-specific articulatory parameters, based on well-established and robust motor control parameters, in the same experimental setup as the MEG brain recordings and in temporal and spatial co-register with the brain data. The analytic approach described here provides new capabilities for testing hypotheses concerning the types of kinematic information that are encoded and processed within specific components of the speech neuromotor system.

Disruption of epithelium integrity by inflammation-associated fibroblasts through prostaglandin signaling.

Inflammation-associated fibroblasts (IAFs) are associated with progression and drug resistance of chronic inflammatory diseases such as inflammatory bowel disease (IBD), but their direct impact on epithelial cells is unknown. Here, we developed an in vitro model whereby human colon fibroblasts are induced by specific cytokines and recapitulate key features of IAFs in vivo. When cocultured with patient-derived colon organoids (colonoids), IAFs induced rapid colonoid expansion and barrier disruption due to swelling and rupture of individual epithelial cells. Colonoids cocultured with IAFs also show increased DNA damage, mitotic errors, and proliferation arrest. These IAF-induced epithelial defects are mediated by a paracrine pathway involving prostaglandin E2 and its receptor EP4, leading to protein kinase A -dependent activation of the cystic fibrosis transmembrane conductance regulator. EP4-specific chemical inhibitors effectively prevented IAF-induced colonoid swelling and restored normal proliferation and genome stability. These findings reveal a mechanism by which IAFs could promote and perpetuate IBD and suggest a therapeutic avenue to mitigate inflammation-associated epithelial injury.

Effectiveness of team-focused CPR on in-hospital CPR quality and outcomes.

Objective: We sought to identify changes in neurological outcome over time following initial training and subsequent implementation of team-focused CPR in an inpatient setting where responders practice specific roles with emphasis on minimally interrupted chest compressions and early defibrillation. Methods: This retrospective pre- vs post-intervention study was conducted at an urban 900-bed teaching hospital and Level I Cardiac Resuscitation Center. We included adult patients suffering in-hospital cardiac arrest occurring in non-emergency department and non-intensive care unit areas who received CPR and/or defibrillation. We compared survival with good neurological outcome at time of hospital discharge in the one-year periods before and after implementation of team-focused CPR. To investigate skill degradation, we compared cumulative survival with good neurological outcome in 3-month intervals against the before team-focused CPR baseline. Trained research associates abstracted explicitly defined variables from electronic health records using a standardized form and data dictionary to achieve consistency between collaborators. Results: Of 296 IHCAs, 207 patients met inclusion criteria and were analyzed. In 104 patients before team-focused CPR initiation, survival with good neurological outcome was 21%. In the 12-month period following team-focused CPR initiation, survival with good neurological outcome was 31% in 101 patients, risk difference 9.9% (95% CI -2 to 22%; p = 0.14). By quarterly time intervals, following team-focused CPR implementation, the cumulative survival with good neurological outcome at 3 months was 42%; at 6 months 37%; at 9 months 31%; and at 12 months 31%. Conclusion: In our single-institution implementation of team-focused CPR for in-hospital cardiac arrest, outcomes significantly improved at 6 months before declining towards baseline.

Examining the Potential of Pharmacies to Expand Pre-Exposure Prophylaxis Access Along Georgia's Fixed-Route Public Transit: A Geospatial Analysis.

BACKGROUND: Despite accounting for more than half of new Human Immunodeficiency Virus diagnoses in the United States, the South has fewer than 30% of all pre-exposure prophylaxis users. Pre-exposure prophylaxis access geospatial analyses have focused on drive time but analyses along public transit routes have not been evaluated. Given the proximity to pharmacists and pharmacies, involvement in pre-exposure prophylaxis services may increase access and uptake of this preventative health need. OBJECTIVE: The objectives were to compare the rate of pre-exposure prophylaxis uptake between Georgia counties with and without public transit, to assess the geospatial accessibility of services along public transit, and to evaluate the potential impact of expanding pre-exposure prophylaxis services to community pharmacies. METHODS: Pre-exposure prophylaxis uptake rates between counties with and without public transit were compared using the Mann-Whitney U test. Geospatial analysis was performed using ArcGIS Pro and Geoda. The Pearson correlation coefficient was used to determine the relationship between pre-exposure prophylaxis uptake rates and population and county characteristics. Spatial analysis was completed to uncover predictors for pre-exposure prophylaxis uptake rates. Increased access to pre-exposure prophylaxis along public transit was calculated by reporting the number of counties that would experience at least a 50% increase in pre-exposure prophylaxis access through community pharmacies. RESULTS: Pre-exposure prophylaxis uptake is significantly higher in Georgia counties with versus without public transit (P < 0.001). Pre-exposure prophylaxis rate is positively correlated with the accessibility of community pharmacies and pre-exposure prophylaxis clinics along fixed-route public transit (R2 = 0.524). Among pre-exposure prophylaxis clinics, 44% are inaccessible by public transit alone. Community pharmacies are significantly more widely distributed and accessible along public transit routes than pre-exposure prophylaxis clinics. CONCLUSION: Transportation remains a barrier to accessing pre-exposure prophylaxis. Georgia community pharmacies along public transit may serve as a solution to pre-exposure prophylaxis care access barriers.

Collaborative drug therapy modification (CDTM): Facilitators, barriers, and perceptions of individual pharmacist participation in Georgia.

BACKGROUND: Georgia Board of Pharmacy (BOP) regulations permit pharmacists to engage in collaborative drug therapy modification (CDTM) with physicians, allowing them to perform patient assessments, adjust pharmacotherapy, and order laboratory tests. Pharmacist-led CDTM can positively affect health outcomes leading to reduced healthcare expenditures. CDTM is underutilized, with < 1% of Georgia pharmacists holding an active license to practice CDTM. OBJECTIVE(S): The objective of this study was to examine CDTM licensed pharmacists' perceptions of facilitators and barriers in providing CDTM. METHODS: Georgia-licensed CDTM pharmacists were invited to participate in a 60-minute qualitative interview. Interview questions were developed from electronic survey responses. The interview was designed to elicit information regarding perceived benefits and barriers to CDTM implementation. Guided by the Consolidated Framework for Implementation Research, thematic analysis was applied to identify themes using ATLAS.ti software to code. Themes were described qualitatively and prevalence of each was reported. RESULTS: Nine interviews were conducted, and data saturation was achieved at interview 6. After resolution of discrepancies, 100% coding agreement was reached among 2 independent researchers. Nine themes were identified, and each was categorized as a facilitator or barrier to establishing pharmacist-led CDTM in Georgia. Themes associated with facilitating were (prevalence %) (1) practice autonomy (100), (2) personal attributes (100), (3) having support (100), and (4) institutional logistics (88). Barrier themes included issues concerning (5) the Georgia BOP (100), (6) pharmacist autonomy (88), (7) lack of provider status (88), (8) institutional restrictions (75), and (9) personal development (e.g., confidence) (22). CONCLUSION: Facilitators to the establishment of pharmacist-led CDTM exist and pharmacists can capitalize on these to create successful CDTM programs. Barriers are varied, and it may be difficult to systematically address individual barriers such as pharmacist autonomy and personal development. Barriers associated with institutional restrictions, the Georgia BOP, and lack of provider status can likely be removed or addressed by policy.

Improving biosensor accuracy and speed using dynamic signal change and theory-guided deep learning.

False results and time delay are longstanding challenges in biosensing. While classification models and deep learning may provide new opportunities for improving biosensor performance, such as measurement confidence and speed, it remains a challenge to ensure that predictions are explainable and consistent with domain knowledge. Here, we show that consistency of deep learning classification model predictions with domain knowledge in biosensing can be achieved by cost function supervision and enables rapid and accurate biosensing using the biosensor dynamic response. The impact and utility of the methodology were validated by rapid and accurate quantification of microRNA (let-7a) across the nanomolar (nM) to femtomolar (fM) concentration range using the dynamic response of cantilever biosensors. Data augmentation and cost function supervision based on the consistency of model predictions and experimental observations with the theory of surface-based biosensors improved the F1 score, precision, and recall of a recurrent neural network (RNN) classifier by an average of 13.8%. The theory-guided RNN (TGRNN) classifier enabled quantification of target analyte concentration and false results with an average prediction accuracy, precision, and recall of 98.5% using the initial transient or entire dynamic response, which is indicative of high prediction accuracy and low probability of false-negative and false-positive results. Classification scores were used to establish new relationships among biosensor performance characteristics (e.g., measurement confidence) and design parameters (e.g., inputs and hyperparameters of classification models and data acquisition parameters) that may be used for characterizing biosensor performance.

Survey of Georgia community pharmacists' needs to engage in advanced community pharmacy services.

BACKGROUND: Community pharmacists improve health, reduce fragmentation in care, lower health costs, and improve health outcomes. In Georgia, pharmacists are able to enter collaborative drug therapy management protocols, such as hypertension management, with a collaborating physician, which may allow pharmacists to provide advanced community pharmacy services (ACPS), however few Georgia pharmacists have this licensure. No program(s) exist that empower pharmacists to successfully engage in ACPS across the state of Georgia nor trains pharmacists to successfully engage in collaborative practice. OBJECTIVE: The goal of this project was to explore community pharmacists' perception, confidence, and engagement in ACPS and how this can improve access to care in Georgia. METHODS: Six hundred one independent community pharmacists were sent an electronic survey May 13, 2022, with weekly email reminders through June 17, 2022. Results were analyzed with the independent sample t test. Thematic analysis was completed on open response survey questions. RESULTS: Ninety responses were received (15% response rate). In the majority of survey outcomes, no differences were found in needs for success between rural versus urban pharmacists. Pharmacies with a smaller technician-to-pharmacists ≤2 (staffing) ratios identified billing for services as a higher priority need for success for them to confidently engage in ACPS (P = 0.012) while pharmacies with a higher technician-to-pharmacists >2 (staffing) ratio agreed a larger need was in optimization of current workflow to allow for advanced community pharmacy service incorporation (P = 0.034). All community pharmacists agreed they would require expansion in staffing and the qualities desired for additional hires to support ACPS include ambition, proficiency, and communication skills. CONCLUSION: Numerous needs for success exist for community pharmacists to feel comfortable and confident to engage in ACPS. Addressing these needs may increase community pharmacist impact through increasing utilization of these services.

Reduction of Biosensor False Responses and Time Delay Using Dynamic Response and Theory-Guided Machine Learning.

Here, we provide a new methodology for reducing false results and time delay of biosensors, which are barriers to industrial, healthcare, military, and consumer applications. We show that integrating machine learning with domain knowledge in biosensing can complement and improve the biosensor accuracy and speed relative to the performance achieved by traditional regression analysis of a standard curve based on the biosensor steady-state response. The methodology was validated by rapid and accurate quantification of microRNA across the nanomolar to femtomolar range using the dynamic response of cantilever biosensors. Theory-guided feature engineering improved the performance and efficiency of several classification models relative to the performance achieved using traditional feature engineering methods (TSFRESH). In addition to the entire dynamic response, the technique enabled rapid and accurate quantification of the target analyte concentration and false-positive and false-negative results using the initial transient response, thereby reducing the required data acquisition time (i.e., time delay). We show that model explainability can be achieved by combining theory-guided feature engineering and feature importance analysis. The performance of multiple classifiers using both TSFRESH- and theory-based features from the biosensor's initial transient response was similar to that achieved using the entire dynamic response with data augmentation. We also show that the methodology can guide design of experiments for high-performance biosensing applications, specifically, the selection of data acquisition parameters (e.g., time) based on potential application-dependent performance thresholds. This work provides an example of the opportunities for improving biosensor performance, such as reducing biosensor false results and time delay, using explainable machine learning models supervised by domain knowledge in biosensing.

Differential effects of aneuploidy on growth and differentiation in human intestinal stem cells.

Aneuploidy, a near ubiquitous genetic feature of tumors, is a context-dependent driver of cancer evolution; however, the mechanistic basis of this role remains unclear. Here, by inducing heterogeneous aneuploidy in non-transformed human colon organoids (colonoids), we investigate how the effects of aneuploidy on cell growth and differentiation may promote malignant transformation. Single-cell RNA sequencing reveals that the gene expression signature across over 100 unique aneuploid karyotypes is enriched with p53 responsive genes. The primary driver of p53 activation is karyotype complexity. Complex aneuploid cells with multiple unbalanced chromosomes activate p53 and undergo G1 cell-cycle arrest, independent of DNA damage and without evidence of senescence. By contrast, simple aneuploid cells with 1-3 chromosomes gained or lost continue to proliferate, demonstrated by single cell tracking in colonoids. Notably, simple aneuploid cells exhibit impaired differentiation when niche factors are withdrawn. These findings suggest that while complex aneuploid cells are eliminated from the normal epithelium due to p53 activation, simple aneuploid cells can escape this checkpoint and may contribute to niche factor-independent growth of cancer-initiating cells.

Accelerated Engineering of Optimized Functional Composite Hydrogels via High-Throughput Experimentation.

The Materials Genome Initiative (MGI) seeks to accelerate the discovery and engineering of advanced materials via high-throughput experimentation (HTE), which is a challenging task, given the common trade-off between design for optimal processability vs performance. Here, we report a HTE method based on automated formulation, synthesis, and multiproperty characterization of bulk soft materials in well plate formats that enables accelerated engineering of functional composite hydrogels with optimized properties for processability and performance. The method facilitates rapid high-throughput screening of hydrogel composition-property relations for multiple properties in well plate formats. The feasibility and utility of the method were demonstrated by application to several functional composite hydrogel systems, including alginate/poly(N-isopropylacrylamide) (PNIPAM) and poly(ethylene glycol) dimethacrylate (PEGDMA)/poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) hydrogels. The HTE method was leveraged to identify formulations of conductive PEGDMA/PEDOT:PSS composite hydrogels for optimized performance and processability in three-dimensional (3D) printing. This work provides an advance in experimental methods based on automated dispensing, mixing, and sensing for the accelerated engineering of soft functional materials.

Disruption of Epithelium Integrity by Inflammation-Associated Fibroblasts through Prostaglandin Signaling: IAFs disrupt colon epithelium via PGE2-EP4.

Inflammation-associated fibroblasts (IAFs) are associated with the progression and drug resistance of chronic inflammatory diseases such as inflammatory bowel disease (IBD), but their direct impact on epithelial function and architecture is unknown. In this study, we developed an in vitro model whereby human colon fibroblasts are induced to become IAFs by specific cytokines and recapitulate key features of IAFs in vivo. When co-cultured with patient-derived colon organoids (colonoids), IAFs induced rapid colonoid swelling and barrier disruption due to swelling and rupture of individual epithelial cells. Epithelial cells co-cultured with IAFs also exhibit increased DNA damage, mitotic errors, and proliferation arrest. These IAF-induced epithelial defects are mediated through a paracrine pathway involving prostaglandin E2 (PGE2) and the PGE2 receptor EP4, leading to PKA-dependent activation of the CFTR chloride channel. Importantly, EP4-specific chemical inhibitors effectively prevented colonoid swelling and restored normal proliferation and genome stability of IAF-exposed epithelial cells. These findings reveal a mechanism by which IAFs could promote and perpetuate IBD and suggest a potential treatment to mitigate inflammation-associated epithelial injury.

Georgia community pharmacies and clinics: An evaluation of health outcomes and care access.

BACKGROUND: Care access remains a major social determinant of health. Safety net clinics may not be numerically sufficient to meet the health care demand for vulnerable populations. Community pharmacists remain a trusted health care provider and serve as first-line care access points. To date, Georgia care access points by safety net clinics and community pharmacies have not been compared. OBJECTIVES: This study sought to evaluate care access across Georgia. County health outcomes and health factor rankings were compared with mortality prevalence of respiratory disease, diabetes mellitus, kidney disease, and a composite of ambulatory care sensitive conditions emergency department (ER) utilization and hospital discharge. In addition, this study sought to determine whether care access points improve if community pharmacies were to provide primary care services. DESIGN AND OUTCOME MEASURES: Geographic information systems mapping was used to locate safety net clinics and community pharmacies. Care access difference was analyzed using a 2-sample t test and health outcomes and rankings were evaluated using ordinary least square regression analysis. RESULTS: A significant difference in care access points was found between safety net clinics and community pharmacies across the state of Georgia (P < 0.05). Mortality prevalence for respiratory disease (P < 0.01), diabetes mellitus (P < 0.1), kidney disease (P < 0.05), ER utilization (P < 0.01), and hospital discharge (P < 0.01) was lower in counties in the top 50% than the bottom 50% health outcome ranking and health factor ranking. Approximately 95% of counties (n = 151) would experience more than a 50% increase in primary care access points by way of community pharmacies. CONCLUSION: Community pharmacies are well positioned to address primary care disease states, reduce health care resource strain, and decrease preventable health care resource utilization. Leveraging pharmacists to provide primary care services can address care access issues and may improve care quality and reduce preventable hospitalizations and ER utilization in Georgia.

A narrative review of the role of the Male Stress Incontinence Grading Scale in the surgical management of male stress urinary incontinence.

Background and Objective: Surgical treatment for male stress urinary incontinence (SUI) includes transobturator slings and artificial urinary sphincters (AUSs). Historically, 24-hour pad weights have been used to objectively grade the severity of male SUI and guide management decisions. In 2016, the Male Stress Incontinence Grading Scale (MSIGS) was developed as a scoring system for the standing cough test (SCT). This test can be performed at the time of initial consultation and is non-invasive, with significantly less burden to the patient compared to historical measures of male SUI. Methods: A review of the reconstructive literature was conducted using PubMed and Google Scholar, reviewing articles that discuss the development of MSIGS, its correlation with objective measures of male SUI, and its use in guiding the choice of anti-incontinence surgical management. Key Content and Findings: MSIGS has been shown to have a strong positive correlation with the 24-hour pad weight test and the subjective patient-reported pads per day (PPD). An MSIGS of 3 or 4 is used to recommend a patient for AUS placement and a score of 1 or 2 for male sling placement. Patient reported satisfaction rates were 95% for AUS and 96.5% for sling. Further, over 91% of men in the study reported they would recommend their selected procedure to other men with a similar condition. Conclusions: The MSIGS is a non-invasive, efficient, and cost-effective way to evaluate men with SUI. The in-office SCT can be quickly and easily adopted into any clinical practice and provides immediate objective information that can be used to better counsel patients on anti-incontinence surgery selection.

A Scoping Review for Debate-Style Journal Clubs in Health Professional Education.

OBJECTIVES: The objectives of this scoping review are to (1) describe the available literature regarding the utility of the debate-style journal club for health professional learners on literature evaluation skills and (2) report the themes found within debate-style journal club research and assessments in the context of professional education. FINDINGS: A total of 27 articles written in the English language were included in this scoping review. Published evaluations of debate-style journal clubs have been predominantly based in the pharmacy profession (48%, n = 13), but are reported in other health professions, such as medicine (22%, n = 6), dentistry (15%, n = 4), nursing (7%, n = 2), occupational therapy (4%, n = 1), and physical therapy (4%, n = 1), as well. The skills assessed in these studies often included critical literature evaluation, application of literature to patient care, critical thinking, knowledge retention, use of supporting literature, and debate-specific skills. Learners typically reported better understanding and application of the literature, and enjoying the experience more than traditional journal clubs, but note the increased assessor and learner time requirement for debating. Pharmacy learner-specific articles more often utilized a traditional, team-based debate format, incorporated grading rubrics for skill assessment and debate performance, and included a grading component for the debate in the course. SUMMARY: Debate-style journal clubs are well-received by learners but require an additional time commitment. Debate platforms, format, rubric use and validation, and outcome assessment vary across published reports.

Association of Life's Simple 7 and ideal cardiovascular health in American Indians/Alaska Natives.

OBJECTIVE: American Indians and Alaska Natives (AI/ANs) are an understudied population at high risk for cardiovascular diseases (CVDs); little is known about contextual factors contributing to CVDs in AI/ANs. This study examined the association of Life's Simple 7 (LS7) factors and social determinants of health (SDH) with CVD outcomes in a nationally representative sample of AI/ANs. METHODS: We conducted a cross-sectional study of 8497 AI/ANs using 2017 Behavioural Risk Factor Surveillance Survey data. Individual LS7 factors were summarised as ideal and poor levels. Coronary heart disease, myocardial infarction and stroke were defined as CVD outcomes. Healthcare access measures represented SDH. Logistic regression analyses examined associations of LS7 factors and SDH with CVD outcomes. Population attributable fractions (PAFs) quantified individual contributions of LS7 factors to CVD outcomes. RESULTS: N=1,297 (15%) participants with CVD outcomes were identified. Smoking, physical inactivity, diabetes, hypertension and hyperlipidaemia were LS7 factors associated with CVD outcomes. Hypertension was the largest contributor to CVD (aPAF 42%; 95% CI 37% to 51%), followed by hyperlipidaemia (aPAF 27%; 95% CI 17% to 36%) and diabetes (aPAF 18%; 95% CI 7% to 23%). Compared with individuals with poor LS7 levels, participants with ideal levels showed 80% lower odds of CVD outcomes (aOR 0.20; 95% CI 0.16 to 0.25). Access to health insurance (aOR 1.43, 95% CI 1.08 to 1.89) and a regular care provider (aOR 1.47, 95% CI 1.24 to 1.76) were associated with CVD outcomes. CONCLUSIONS: Effective interventions are needed to address SDH and attain ideal LS7 factors to improve cardiovascular health among AI/ANs.

Case report: Development of vesicouterine and vesicovaginal fistulas after uterine rupture.

Vesicouterine fistulas are an extremely rare fistula occurring between the bladder and uterus and most commonly occur after lower segment cesarean sections. There are fewer than 100 case reports documenting vesicouterine fistulas, with most managed with open or laparoscopic surgical techniques. We present a novel case, including diagnostic evaluation and robotic-assisted repair, of a simultaneous vesicovaginal and vesicouterine fistula that developed after a uterine rupture that was complicated by multiple cystotomies. A robotic approach affords good visibility of the deep pelvis while still allowing for mobilization of the omentum as an interposition graft, with the benefit of a minimally-invasive approach.

A sweet solution to complex microprinting.

A simple sugar mixture transfers functional components to surfaces with intricate geometry.

Speech Kinematics and Coordination Measured With an MEG-Compatible Speech Tracking System.

Articulography and functional neuroimaging are two major tools for studying the neurobiology of speech production. Until recently, however, it has generally not been possible to use both in the same experimental setup because of technical incompatibilities between the two methodologies. Here we describe results from a novel articulography system dubbed Magneto-articulography for the Assessment of Speech Kinematics (MASK), which we used to derive kinematic profiles of oro-facial movements during speech. MASK was used to characterize speech kinematics in two healthy adults, and the results were compared to measurements from a separate participant with a conventional Electromagnetic Articulography (EMA) system. Analyses targeted the gestural landmarks of reiterated utterances /ipa/, /api/ and /pataka/. The results demonstrate that MASK reliably characterizes key kinematic and movement coordination parameters of speech motor control. Since these parameters are intrinsically registered in time with concurrent magnetoencephalographic (MEG) measurements of neuromotor brain activity, this methodology paves the way for innovative cross-disciplinary studies of the neuromotor control of human speech production, speech development, and speech motor disorders.

A Scoping Review Evaluating the Effect of SGLT-2 Inhibitors on Insulin Dose Requirements in Insulin-Dependent Patients With Type 2 Diabetes.

OBJECTIVE: Assess evidence describing the effect of Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors on total daily insulin (TDI) requirements in insulin-dependent patients with type 2 diabetes. DATA SOURCES: A scoping review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Protocols and Scoping Reviews (PRISMA-ScR) guidelines. The search was conducted in PubMed; citation mapping was completed in Web of Science. Filters for human studies, English language, and a publication date, from January 1, 2005 to April 12, 2021, were applied. STUDY SELECTION AND DATA EXTRACTION: Studies assessing insulin dose requirements with concurrent use of an SGLT2 inhibitor for patients with type 2 diabetes were included. DATA SYNTHESIS: Sixteen studies were included and demonstrated that addition of an SGLT2 inhibitor typically reduced TDI requirements. Insulin reductions were often statistically significant, occurring in studies evaluating (1) within subjects who received SGLT2 inhibitors, and (2) between subjects receiving SGLT2 inhibitors versus placebo. Compared with placebo, insulin dose reduction ranged from -0.72 to -19.2 units. However, studies were relatively small, not designed to assess TDI change, and some utilized fixed dose insulin protocols or empiric insulin dose reductions. CONCLUSIONS: Lowering insulin requirements may have benefits, such as decreased hypoglycemia risk, insulin resistance, and cost. Addition of an SGLT2 inhibitor may modestly reduce TDI requirements for patients with type 2 diabetes. Evidence indicating SGLT2 inhibitor use reduces TDI may lead to additional implementation in practice and inform future research. Further research is needed to clarify insulin type (i.e., basal or prandial) and degree of TDI reduction expected with addition of an SGLT2 inhibitor.

Brain EEG Time-Series Clustering Using Maximum-Weight Clique.

Brain electroencephalography (EEG), the complex, weak, multivariate, nonlinear, and nonstationary time series, has been recently widely applied in neurocognitive disorder diagnoses and brain-machine interface developments. With its specific features, unlabeled EEG is not well addressed by conventional unsupervised time-series learning methods. In this article, we handle the problem of unlabeled EEG time-series clustering and propose a novel EEG clustering algorithm, that we call mwcEEGc. The idea is to map the EEG clustering to the maximum-weight clique (MWC) searching in an improved Fréchet similarity-weighted EEG graph. The mwcEEGc considers the weights of both vertices and edges in the constructed EEG graph and clusters EEG based on their similarity weights instead of calculating the cluster centroids. To the best of our knowledge, it is the first attempt to cluster unlabeled EEG trials using MWC searching. The mwcEEGc achieves high-quality clusters with respect to intracluster compactness as well as intercluster scatter. We demonstrate the superiority of mwcEEGc over ten state-of-the-art unsupervised learning/clustering approaches by conducting detailed experimentations with the standard clustering validity criteria on 14 real-world brain EEG datasets. We also present that mwcEEGc satisfies the theoretical properties of clustering, such as richness, consistency, and order independence.