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ABSTRACTDecades of ongoing research has established that oral microbial communities play a role in oral diseases such as periodontitis and caries. Yet the detection of oral bacteria and the profiling of oral polymicrobial communities currently rely on methods that are costly, slow, and technically complex, such as qPCR or next-generation sequencing. For the widescale screening of oral microorganisms suitable for point-of-care settings, there exists the need for a low-cost, rapid detection technique. Here, we tailored the novel CRISPR-Cas-based assay SHERLOCK for the species-specific detection of oral bacteria. We developed a computational pipeline capable of generating constructs suitable for SHERLOCK and experimentally validated the detection of seven oral bacteria. We achieved detection within the single-molecule range that remained specific in the presence of off-target DNA found within saliva. Further, we adapted the assay for detecting target sequences directly from unprocessed saliva samples. The results of our detection, when tested on 30 healthy human saliva samples, fully aligned with 16S rRNA sequencing. Looking forward, this method of detecting oral bacteria is highly scalable and can be easily optimized for implementation at point-of-care settings.

Purpose. To present the results of a strengths, weaknesses, opportunities and threats (SWOT) analysis used as part of a process aimed at reorganising services provided within a pediatric rehabilitation programme (PRP) in Quebec, Canada and to report the perceptions of the planning committee members regarding the usefulness of the SWOT in this process. Method. Thirty-six service providers working in the PRP completed a SWOT questionnaire and reported what they felt worked and what did not work in the existing model of care. Their responses were used by a planning committee over a 12-month period to assist in the development of a new service delivery model. Committee members shared their thoughts about the usefulness of the SWOT. Results. Current programme strengths included favourable organisational climate and interdisciplinary work whereas weaknesses included lack of psychosocial support to families and long waiting times for children. Opportunities included working with community partners, whereas fear of losing professional autonomy with the new service model was a threat. The SWOT results helped the planning committee redefine the programme goals and make decisions to improve service coordination. SWOT analysis was deemed as a very useful tool to help guide service reorganisation. Conclusions. SWOT analysis appears to be an interesting evaluation tool to promote awareness among service providers regarding the current functioning of a rehabilitation programme. It fosters their active participation in the reorganisation of a new service delivery model for pediatric rehabilitation. [ABSTRACT FROM AUTHOR]

Improving the quality of care for hip arthroplasty (replacement) patients requires the systematic evaluation of clinical performance of implants and the identification of “outlier” devices that have an especially high risk of reoperation (“revision”). Postmarket surveillance of arthroplasty implants, which rests on the analysis of large patient registries, has been effective in identifying outlier implants such as the ASR metal-on-metal hip resurfacing device that was recalled. Although identifying an implant as an outlier implies a causal relationship between the implant and revision risk, traditional signal detection methods use classical biostatistical methods. The field of probabilistic graphical modeling of causal relationships has developed tools for rigorous analysis of causal relationships in observational data. The purpose of this study was to evaluate one causal discovery algorithm (PC) to determine its suitability for hip arthroplasty implant signal detection. Simulated data were generated using distributions of patient and implant characteristics, and causal discovery was performed using the TETRAD software package. Two sizes of registries were simulated: (1) a statewide registry in Michigan and (2) a nationwide registry in the United Kingdom. The results showed that the algorithm performed better for the simulation of a large national registry. The conclusion is that the causal discovery algorithm used in this study may be a useful tool for implant signal detection for large arthroplasty registries; regional registries may only be able to only detect implants that perform especially poorly.

Abstract Background The impact of a pediatric rehabilitation service delivery reorganization to improve access to services on parents' and service providers' perception of service quality was evaluated. Child-, family-, service- and service provider-related characteristics possibly associated with these perceptions were explored. Methods Perceptions were measured using the Measure of Processes of Care tools and open ended questions before (2007), during (2008) and following (2009) service reorganization. Child and family characteristics, services received and service provider data were documented. Mean MPOC scores were compared over time (ANOVAs and Generalized Estimating Equations) and t-tests, correlations and ANOVAs determined whether the characteristics influenced scores. Results Families' (n = 222) and service providers' (n = 129) perceptions of quality were high in 2007 (3.67 to 6.31/7) and remained high over the next 2 years (p ≥ 0.16). Two MPOC domain scores (Respectful care and Providing general information) were consistently scored the highest (mean ≥ 5.66/7) and the lowest (mean ≤ 4.75/7), respectively. Families with more education and those with children 12-21 years old tended to attribute lower MPOC scores. Participants were generally satisfied with the new service model and recommendations included improving information exchange. Conclusions Results suggest that it is possible to reorganize pediatric rehabilitation services while maintaining quality.

Background: Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice., Methods: The National Liver Cancer Screening Trial is an adaptive pragmatic randomized phase IV trial, which began enrollment in January 2024, comparing ultrasound-based versus biomarker-based screening in 5500 patients with chronic hepatitis B infection or cirrhosis from any etiology. Eligible patients are randomly assigned in a 1:1 ratio to semi-annual screening with ultrasound ± alpha-fetoprotein (arm A) or semi-annual screening with GALAD (arm B). Randomization is stratified by enrollment site, liver disease severity (per Child-Pugh class), liver disease etiology (viral, nonviral, and noncirrhotic HBV), and sex. Patients are being recruited from 15 sites (a mix of tertiary care academic referral centers, safety-net health systems, and large community health systems) over a 3-year period, and the primary endpoint, reduction in late-stage HCC, will be assessed at the end of year 5.5., Discussion: The results of this trial will inform the best strategy for HCC screening and early-stage detection in patients with chronic liver diseases. If GALAD shows superiority, HCC screening would primarily shift from an ultrasound-based strategy to the adoption of the biomarker panel., Trial Registration: NCT06084234., Trial Status: The TRACER Study is actively enrolling., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs. We analyzed the training set to identify candidate biomarker combination panels using biomarkers across laboratories, and we applied the fixed panels to the validation set. The panels identified in the training set, CA19-9 with CA199.STRA, LRG1, TIMP-1, TGM2, THSP2, ANG, and MUC16.STRA, achieved consistent performance in the validation set. The panel of CA19-9 with the glycan biomarker CA199.STRA improved sensitivity from 0.44 with 0.98 specificity for CA19-9 alone to 0.71 with 0.98 specificity (p < 0.001, 1000-fold bootstrap). Similarly, CA19-9 combined with the protein biomarker LRG1 and CA199.STRA improved specificity from 0.16 with 0.94 sensitivity for CA19-9 to 0.65 with 0.89 sensitivity (p < 0.001, 1000-fold bootstrap). We further validated significantly improved performance using biomarker panels that did not include CA19-9. This study establishes the effectiveness of a coordinated study of previously discovered biomarkers and identified panels of those biomarkers that significantly increased the sensitivity and specificity of early-stage PDAC detection in a rigorous validation trial., Competing Interests: Declaration of competing interest AM is a consultant for Tezcat Biotechnologies and is a co-inventor on a patent that has been licensed from Johns Hopkins University by Thrive Earlier Detection (an Exact Sciences company). RB received research funding from Immunovia and Freenome and serves as on the advisory board for Immunovia. The authors declare no other reported potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This article reports a systematic literature review that examined past research exploring the effectiveness of collaborative Augmented Reality (AR) enabled instruction, in higher education contexts. To be included, an article should consist of an experimental study investigating the use of collaborative AR for learning in higher education settings. An initial search was conducted on five databases that resulted in a total of 2537 articles, of which 20 were finalized for this review. The main findings suggest that AR-enabled collaborative learning benefits students' overall learning outcomes and provides a positive collaboration experience in higher education settings. Further research is needed to determine the interaction elements, collaboration mechanisms, and information representation through AR that would potentially enhance student learning outcomes. This article concludes by discussing the implications of these findings, identifying challenges and strategies for developing effective collaborative AR-enabled learning content., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Localized prostate tumors show significant spatial heterogeneity, with regions of high-grade disease adjacent to lower grade disease. Consequently, prostate cancer biopsies are prone to sampling bias, potentially leading to underestimation of tumor grade. To study the clinical, epidemiologic, and molecular hallmarks of this phenomenon, we conducted a prospective study of grade upgrading: differences in detected prostate cancer grade between biopsy and surgery., Methods: We established a prospective, multi-institutional cohort of men with grade group 1 (GG1) prostate cancer on biopsy who underwent radical prostatectomy. Upgrading was defined as detection of GG2+ in the resected tumor. Germline DNA from 192 subjects was subjected to whole-genome sequencing to quantify ancestry, pathogenic variants in DNA damage response genes, and polygenic risk., Results: Of 285 men, 67% upgraded at surgery. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores were significantly associated with upgrading. No assessed genetic risk factor was predictive of upgrading, including polygenic risk scores for prostate cancer diagnosis., Conclusions: In a cohort of patients with low-grade prostate cancer, a majority upgraded at radical prostatectomy. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores portended the presence of higher-grade disease, while germline genetics was not informative in this setting. Patients with low-risk prostate cancer, but elevated PSA density or percent cancer in positive biopsy cores, may benefit from repeat biopsy, additional imaging or other approaches to complement active surveillance., Impact: Further risk stratification of patients with low-risk prostate cancer may provide useful context for active surveillance decision-making., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Despite effectiveness of the implantable cardioverter-defibrillator (ICD) in saving patients with life-threatening ventricular arrhythmias (VAs), the temporal occurrence of VA after ICD implantation is unpredictable., Objective: The study aimed to apply machine learning (ML) to intracardiac electrograms (IEGMs) recorded by ICDs as a unique biomarker for predicting impending VAs., Methods: The study included 13,516 patients who received Biotronik ICDs and enrolled in the CERTITUDE registry between January 1, 2010, and December 31, 2020. Database extraction included IEGMs from standard quarterly transmissions and VA event episodes. The processed IEGM data were pulled from device transmissions stored in a centralized Home Monitoring Service Center and reformatted into an analyzable format. Long-range (baseline or first scheduled remote recording), mid-range (scheduled remote recording every 90 days), or short-range predictions (IEGM within 5 seconds before the VA onset) were used to determine whether ML-processed IEGMs predicted impending VA events. Convolutional neural network classifiers using ResNet architecture were employed., Results: Of 13,516 patients (male, 72%; age, 67.5 ± 11.9 years), 301,647 IEGM recordings were collected; 27,845 episodes of sustained ventricular tachycardia or ventricular fibrillation were observed in 4467 patients (33.0%). Neural networks based on convolutional neural networks using ResNet-like architectures on far-field IEGMs yielded an area under the curve of 0.83 with a 95% confidence interval of 0.79-0.87 in the short term, whereas the long-range and mid-range analyses had minimal predictive value for VA events., Conclusion: In this study, applying ML to ICD-acquired IEGMs predicted impending ventricular tachycardia or ventricular fibrillation events seconds before they occurred, whereas midterm to long-term predictions were not successful. This could have important implications for future device therapies., Competing Interests: Disclosures A.L. receives consulting fees from SHL Telemedicine. A number of AI ECG algorithms have been licensed by Mayo Clinic to Anumana, Eko Health, and AliveCor; Mayo Clinic, P.A.F., I.Z.A., and S.J.A. may benefit financially from their commercialization. G.A.U. receives consulting and speaking fees from Biotronik, St Jude Medical, Medtronic, Boston Scientific, Philips BioTel, and Zoll Medical. S.J.A. receives honoraria and consulting and speaking fees from Biotronik, St Jude Medical, Medtronic, Boston Scientific, BioSig Technologies, and MediLynx. All other authors have no relevant relationships to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Partnering for Change (P4C) is an innovative practice model for school-based occupational therapy developed in Canada and informed by a program of research spanning nearly two decades. National and international interest in P4C necessitated development of an explanatory theory to guide implementation in varied contexts. The purpose of this study is to document the process of theory development and to provide an overview of the initial P4C explanatory theory., Methods: Realist evaluation was used to construct an initial explanatory theory of P4C drawing on P4C developers' conceptualisations of the model, document analysis, and analysis of transcripts from interviews and focus groups., Consumer and Community Involvement: No consumers were involved in the study design or analysis., Findings: Four sets of premises expressed as context-mechanism-outcome configurations (CMOCs) comprise the initial explanatory theory of P4C. An abstracted summary of these four sets along with contexts, mechanisms, and outcomes central to the P4C initial explanatory theory is presented. An exemplar CMOC is shared to illustrate how theoretical premises are developed and expressed using realist evaluation., Conclusion: This study advances knowledge regarding the hypothesised core elements of P4C and provides an example of using realist evaluation to advance knowledge in occupational therapy. Preliminary implications for clinical practice are discussed., Plain Language Summary: Partnering for Change (P4C) is a way of providing occupational therapy services in schools that helps all children to learn and participate successfully. P4C was created in Ontario, Canada, and has been researched for almost 20 years. People in different parts of Canada and other countries are interested in trying P4C. As the researchers who created P4C, we think there is a need to explain how it works so it can be used in different places. This study explains how we created a theory to describe P4C. To develop this theory, we used a method called realist evaluation that would help us explain how, why, and in what situations P4C works best. To do this, we analysed documents and transcripts of interviews and focus groups. Our findings are organised into four main ideas, each explained in terms of contexts (the situations), mechanisms (how and why P4C works), and outcomes (the impacts of P4C). One detailed example is given to show how these ideas were formed and work together. In conclusion, our study helps us understand the key parts of P4C and shows how realist evaluation can be used to improve knowledge in occupational therapy. The study also suggests some early ideas on how P4C can be used in practice., (© 2024 The Author(s). Australian Occupational Therapy Journal published by John Wiley & Sons Australia, Ltd on behalf of Occupational Therapy Australia.)

Telerehabilitation is proposed as a promising avenue to enhance service accessibility for Indigenous communities, yet its application for Indigenous children remains relatively unexplored. This scoping review followed the PRISMA-ScR framework to explore current knowledge on the use of telerehabilitation for Indigenous children. Ten scholarly databases, seven grey literature databases, reference searches, and expert consultations were utilised to identify relevant studies. Included articles discussed the use of telerehabilitation provided by rehabilitation professionals (e.g. occupational therapist (OT), physical therapist (PT), speech and language pathologist (SLP) to Indigenous children and/or caregivers. Seven studies were included. Telerehabilitation was explored in different ways, the most common being real-time videoconferencing by SLPs. While some studies explicitly acknowledged cultural responsiveness within both the research process and the intervention, most were not designed for Indigenous children and their caregivers; rather, these participants were included with non-Indigenous participants. Successful implementation and sustainability of telerehabilitation services requires addressing technological limitations, understanding, and respecting diverse worldviews, and co-developing services to meet the unique needs of Indigenous families. Telerehabilitation has been rarely used with Indigenous children and when it was, little attention was given to cultural considerations. These findings emphasise that future telerehabilitation interventions should be truly community-led to ensure cultural relevance.

Knowledge of locations and activities of cis -regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using epigenetic features in one species, making comparisons difficult between species. In contrast, we conducted an interspecies study defining epigenetic states and identifying cCREs in blood cell types to generate regulatory maps that are comparable between species, using integrative modeling of eight epigenetic features jointly in human and mouse in our Validated Systematic Integration (VISION) Project. The resulting catalogs of cCREs are useful resources for further studies of gene regulation in blood cells, indicated by high overlap with known functional elements and strong enrichment for human genetic variants associated with blood cell phenotypes. The contribution of each epigenetic state in cCREs to gene regulation, inferred from a multivariate regression, was used to estimate epigenetic state regulatory potential (esRP) scores for each cCRE in each cell type, which were used to categorize dynamic changes in cCREs. Groups of cCREs displaying similar patterns of regulatory activity in human and mouse cell types, obtained by joint clustering on esRP scores, harbor distinctive transcription factor binding motifs that are similar between species. An interspecies comparison of cCREs revealed both conserved and species-specific patterns of epigenetic evolution. Finally, we show that comparisons of the epigenetic landscape between species can reveal elements with similar roles in regulation, even in the absence of genomic sequence alignment., (© 2024 Xiang et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: Shock-reduction implantable cardioverter-defibrillator programming (SRP) was associated with fewer therapies and improved survival in randomized controlled trials, but real-world studies investigating SRP and associated outcomes are limited., Methods and Results: The BIOTRONIK CERTITUDE registry was linked with the Medicare database. We included all patients with an implantable cardioverter-defibrillator implanted between August 22, 2012 and September 30, 2021 in the United States. SRP was defined as programming to either a therapy rate cutoff ≥188 beats per minute or number of intervals to detection ≥30/40 for treatment. Among 6781 patients (mean 74±9 years; 27% women), 3393 (50%) had SRP. Older age, secondary prevention indication, and device implantation in the southern or western United States were associated with lower use of SRP. The cumulative incidence rate of implantable cardioverter-defibrillator shocks was lower in the SRP group (5.1% shocks/patient year) compared with the non-SRP group (7.2% shocks/patient year) (adjusted hazard ratio [HR], 0.83 [95% CI, 0.73-0.96]; P =0.005). Over a median follow-up of 2.9 years, 739 deaths occurred in the SRP group and 822 deaths occurred in the non-SRP group (adjusted HR, 0.97 [95% CI, 0.88-1.07]; P =0.569). SRP was associated with a lower all-cause mortality among patients without ischemic heart disease compared with patients with ischemic heart disease (adjusted HR, 0.64 [95% CI, 0.48-0.87] versus adjusted HR, 1.02 [95% CI, 0.92-1.14]; P interaction =0.004)., Conclusions: Adoption of SRP is low in real-world clinical practice. Age, clinical variables, and geographic factors are associated with use of SRP. In this study, SRP-associated decrease in mortality was limited to patients without ischemic heart disease.

Introduction: The impact of mRNA-based coronavirus disease-2019 (COVID-19) vaccines on atrial arrhythmias (AA) and ventricular arrhythmias incidence is unknown., Methods: BIOTRONIK Home Monitoring data and Medicare Claims data were utilized to identify individuals implanted with a cardiac implantable electronic device (CIED) between 2010 and 2020 who received one or more doses of COVID-19 vaccine in 2021. The burden of AA (%) in the 3 months postvaccination was compared to those noted in the preceding 3 months using the Wilcoxon signed rank test. Sub-analyses comparing the effects of the influenza vaccine against the COVID-19 vaccine were also evaluated for individuals who received the influenza vaccine in 2020. A 1:1 propensity score match comparison between COVID-19 vaccine and non-vaccinated patients was also performed., Results: First and second doses of the COVID-19 vaccine were administered to 7757 and 6579 individuals with a CIED (age 76.2 ± 9.0 years, 49% males), respectively. While a small but statistically significant increase in the burden of AA was noted in the 3 months postvaccination compared to the preceding 3 months after the first dose of the COVID-19 vaccine (0.43 ± 9.04%, p = .028) a similar rise in AA was found following the influenza vaccine and for matched patients who did not receive the COVID-19 vaccine. No significant difference in device therapies was seen pre- and postvaccination., Conclusions: Though we report a small but significant increase in the number of CIED-detected AAs following vaccination for COVID-19 over a 3-month window, we believe these results correlate more with time and the progressive nature of AF rather than the vaccine itself. While these data should not dissuade from the use of these vaccines, increased vigilance and prompt treatment of AF is required for high-risk groups, specifically males over 70 years of age, following vaccination., (© 2024 Wiley Periodicals LLC.)

Background: Many challenges exist in promoting inclusion in childcare settings. Adequate support from specialized professionals is necessary to create inclusive childcare settings. Understanding which services are being delivered by specialized professionals in childcare contexts is an important first step. The aim of this study was to (1) describe the services currently being delivered by specialized professionals in childcare settings in Quebec (Canada) and (2) seek childcare administrators' perspectives on their preferred services., Methods: An online province-wide descriptive survey was conducted with childcare administrators (n = 344). Questions focused on 11 service delivery dimensions (e.g. professionals involved, children served). Descriptive statistics were calculated., Results: Childcare settings received services from a median of two specialized professionals (IQR [1-4]). Most services were delivered by early childhood special educators (61.3%), speech-language pathologists (57.6%), psycho-educators (43.6%) and occupational therapists (43.3%). Childcare administrators identified these four services as being particularly supportive. Professionals delivered a median of 0.4 h of service per week in each childcare setting (IQR [0.1-3.0]). A high percentage (91.2%) of administrators reported unmet needs for professional support in at least one developmental domain, with a high percentage (57.3%) of administrators identifying needs in the socio-emotional domain. Most (63.3%) expressed a desire to prioritize services for children without an established diagnosis but identified by early childhood educators as having needs for professional support. Most administrators (71.4%) also preferred in-context services., Conclusions: Childcare administrators perceive an important role for specialized professionals in supporting inclusion in their settings. Recommendations emerging are based on the four main professional service needs identified: (1) increasing the intensity and stability of services; (2) providing services for undiagnosed children identified by early childhood educators as having unmet needs; (3) ensuring that services encompassing all developmental domains with a focus on the socio-emotional domain; and (4) prioritizing of in-context services., (© 2024 The Author(s). Child: Care, Health and Development published by John Wiley & Sons Ltd.)