bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teaching Families How to Manage Diabetic Emergencies Using Their Children as Patient Simulators
Authors: Levy Arielle R. , Leo Harmine C. , Joseph Tatiana , Henderson Mélanie , Olivier Patricia , Shayan Yasaman , Buithieu Maria 
Published: June 2024

Objectives
The aims of the study are to develop an insulin pump simulation curriculum using patients as simulators, to evaluate its effectiveness on knowledge, attitudes, and skills necessary for families to manage diabetic emergencies, and to identify ongoing gaps in care.

Methods
Our simulation curriculum developed using Kerns, consisted of 4 stations. A prospective simulation study was conducted at a pediatric tertiary care hospital with a convenience sample of children with type 1 diabetes on the insulin pump program and their families using patients as simulators and their parents as participants. The curriculum's success with developing competent skills was assessed using Kirkpatrick's 4-level evaluation model. Data from satisfaction questionnaires, performance gaps in emergency management, and postsimulation knowledge questionnaires were analyzed to identify ongoing gaps in care using a mixed methods approach.

Results
Among 70 families (169 participants), satisfaction was high (3.7–4.0/4.0) and confidence was increased (mean score 12 ± 0.03/12). Recurrent performance gaps across scenarios were found: misunderstandings about residual insulin during hypoglycemia (35%) and severe hypoglycemia with altered level of consciousness (22%), and failure to identify causes in 13% of simple and 11% of severe hypoglycemia scenarios and overtreating hypoglycemia with glucagon in a conscious patient in 14% of simple hypoglycemia scenarios. Postsimulation knowledge questionnaires revealed improvements in knowledge/management of simple hypoglycemia (mean score 87%), poor knowledge of pump parameters (mean score 56%), excellent knowledge of manipulating pump parameters to prevent emergencies (mean score 100%), and poor knowledge of basal rate concepts (mean score 19%).

Conclusions
Simulation using patient simulators improved management skills and confidence of families facing diabetic emergencies. Ongoing gaps in care were identified and used to enhance the current curriculum. Integrating simulation into insulin pump curricula can enhance patient self-care, safety, and be generalizable to other chronic-care patient-education programs. Future work should evaluate the impact of this curriculum on real-life events and patient outcomes.
A Contemporary Evaluation of the Centers for Medicare and Medicaid Services High-risk Indicators for Carotid Endarterectomy
Authors: Straus Sabrina , Barodi Batol , Zarrintan Sina , Willie-Permor Daniel , Vootukuru Nishita , Malas Mahmoud 
Published: June 2024

Objective:
Compare stroke/death outcomes across carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TFCAS) using Centers for Medicare and Medicaid Services (CMS) high-risk criterion.

Background:
Existing literature has revealed inconsistencies with CMS risk guidelines. With recent approval for TCAR and TFCAS in standard-risk patients, an updated analysis of guidelines is needed.

Methods:
Data from the Vascular Quality Initiative (VQI) (2016–2023) on CEA, TFCAS, or TCAR patients were used. We used inverse probability of treatment weighting to compare in-hospital stroke/death rates across procedures for high-risk criteria: contralateral occlusion (CLO), prior CEA, CAS, radiation, neck surgery, moderate to severe CHF, severe COPD (on home O2), unstable angina, recent MI (<6 mo), and age (≥75 years-old).

Results:
A total of 199,050 patients were analyzed, of whom 122,737 (62%) patients underwent CEA, 50,095 (25%) TCAR, and 26,218 (13%) TFCAS. TCAR had lower odds of stroke/death compared with CEA in patients with CLO [aOR=0.73 (95% CI: 0.55–0.98], P=0.035] and radiation [aOR=0.44 (95% CI: 0.23–0.82), P=0.010]. Contrary to CMS criteria, CEA patients did not have higher stroke/death in patients with prior CEA, CAS, neck surgery, moderate to severe CHF, severe COPD, unstable angina, recent MI, or age (≥75) compared with TCAR and TFCAS.

Conclusions:
While CMS high-risk criteria have traditionally been recognized as contraindications for CEA, our study reveals inconsistencies—with CEA performing similarly to TCAR and significantly better than TFCAS in patients with prior CEA, moderate to severe CHF, recent MI, or age (≥75). As a result, the definition of high-risk criteria may warrant reconsideration.
An Analysis of Water Used and Wasted at Operating Room (OR) Scrub Sinks and Call to Action for Reducing Water Waste
Authors: Hu Carolyn J. , Reilly Margaret , Khan Imadh , Hoel Andrew W. , Sturgeon Cord , Ho Karen J. 
Published: June 2024

Objective:
To model the volume of water used and wasted during wet scrubs at operating room (OR) scrub sinks and identify factors for reducing water waste.

Background:
Wasteful consumption of water by US healthcare systems has not been well characterized.

Methods:
This is a two-component observational study. The first was an observational study of handwashing practices and water usage at scrub sinks in the OR at a single medical center. The second component was a series of two anonymous surveys of surgeons and OR staff to assess hand scrub practices and perspectives. Data from both components were used to estimate the volume of water used and wasted annually at OR scrub sinks.

Results:
The median total volume of water wasted at OR scrub sinks for 34,554 cases over one year is 337,595.6 L (interquartile range 139,010.0;911,210.5). This represents approximately 34.2% of the total volume of water usage associated with wet scrubs (i.e.,water used during scrubbing and wasted after the conclusion of the scrub). Other pertinent findings are that attending surgeons and OR staff perform water scrubs in 25.9% of cases; there are significant differences in scrub type preferences among OR users; the median volume of water wasted in a single wet scrub at timer-controlled sinks is 10 L; and significantly more water is wasted at timer-controlled sinks than knee-operated sinks.

Conclusions:
OR wet scrubs are a source of enormous water waste. We identified scrub sink characteristics and OR user beliefs and behaviors as modifiable factors for water waste reduction. We encourage all institutions and OR users to carefully examine their facility characteristics and practices to implement plans that will conserve water without compromising patient safety.
Collaborative implementation science: a Can-SOLVE CKD case example
Authors: Allu Selina , Beaucage Mary , Donald Maoliosa , Escoto Manuel , Kappel Joanne , Morrin Louise , Soroka Steven D. 
Published: June 2024

ABSTRACT
Research is critical for uncovering new and effective therapies for better health outcomes, yet there remains a significant lag between identifying evidence-based interventions and implementing them into practice. Research teams can often be experienced in evidence generation, but less so in evidence implementation, underscoring the need for more customized tools to support them in this latter step. The implementation stage can be especially challenging given how strategies must be tailored to the unique end users and contexts of a given intervention. Therefore, our patient-oriented kidney research network sought to create an “Implementation Toolkit” and “Pathway to Implementation” guide to help research teams and their operational and clinical partners in implementing their interventions. Importantly, the tools were created using input and feedback from diverse groups, including patient partners, implementation science experts, researchers, operational leaders, and policymakers, all of whom play role in supporting the implementation of health interventions. Our tools are widely applicable to diverse teams, regardless of the intervention or innovation being implemented.

Spanish abstract:

http://links.lww.com/IJEBH/A214
Novel sex-biased outcomes in neuroblastoma are associated with distinct gene expression and chromosomal loss patterns
Authors: Patel Vishwa , Raleigh Mariya , Benhamou Lorraine-Rana E. , Shen Xin , Espinosa Erika C. , Badi Niharika R. , Sheeter Dennis A. , Powers John T. 
Published: June 2024

AbstractThe worst patient outcomes in neuroblastoma are driven by high-risk disease1,2, which is divided into similarly sizedMYCNamplified andMYCNnon-amplified patient subgroups3. Male patients have been reported to have slightly worse outcomes than females in all-patient analyses of multiple studies3,4. However, we show here that inMYCNnon- amplified high-risk and stage 4s low-risk disease, female patients have significantly worse overall survival than males. FemaleMYCNnon-amplified high-risk patients highly expressH19andDLK1, both of which drive cell growthin vitroand are associated with worse outcomes in females but not males. Further, chromosome-specific expression analysis of these patients reveals broad sex disparities in chromosomal patterning, including female-specific retention of chromosome 11q, a pattern typically reserved forMYCN-amplified disease5,6. Finally, we show thatH19, a knownlet-7microRNA target7, sequesterslet-7in females, providing a rationale for worse female survival and reconciling retention of chromosome 11q. We propose that this novel sex-based outcome disparity is driven bylet-7inhibition, expanding on a model of neuroblastoma development wherelet-7mitigation is central to disease pathology8.
The ecology of potentially pathogenicVibriospp. in a seagrass meadow ecosystem
Authors: Gebbe Rebecca , Kesy Katharina , Hallier Dorothea , Brauer Anne , Bertilsson Stefan , Labrenz Matthias , Bengtsson Mia M. 
Published: June 2024

ABSTRACTSeagrass meadow ecosystems offer several valuable ecosystem services in coastal regions around the world. Recent studies have suggested that one such important service is reduction of pathogenic bacteria and specificallyVibriospp. in adjacent waters. The specific mechanisms of pathogen reduction remain unclear, although increased sedimentation has been suggested as one likely process for pathogens to be quenched from the water column. WhetherVibriospp. persist in the sediment or in other compartments of the seagrass meadow is currently not known, but it has been shown that marine surface biofilms can function as reservoirs of pathogenic vibrios. This general feature may also apply to seagrass and sediment surfaces. In this study, we investigated the relative abundance and community ecology ofVibriospp. bacteria in Baltic Sea seagrass meadows using both culturing and culture-independent methods. While we did not detect a significant reduction ofVibriospp., the highest relative abundances ofVibriospp. were observed in the water column above unvegetated sites as compared to seagrass meadows. We also detected high relative abundances ofVibriospp. on seagrass roots, supporting previous observations that marine surfaces are selectively colonized byVibriospp., implying that these habitats are important for the persistence and possibly release ofVibriospp. into the water column. Our results emphasize the need to understand the interactions of pathogenic bacteria with coastal habitats, including interactions with host organisms such as seagrasses that provide biofilm microenvironments, in order to understand how diseases associated with these organisms develop.
Automated Dentate Nucleus Segmentation from QSM Images Using Deep Learning
Authors: Shiraishi Diogo H , Saha Susmita , Adanyeguh Isaac M , Cocozza Sirio , Corben Louise A , Deistung Andreas , Delatycki Martin B , Dogan Imis , Gaetz William , Georgiou-Karistianis Nellie , Graf Simon , Grisoli Marina , Henry Pierre-Gilles , Jarola Gustavo M , Joers James M , Langkammer Christian , Lenglet Christophe , Li Jiakun , Lobo Camila C , Lock Eric F , Lynch David R , Mareci Thomas H , Martinez Alberto R M , Monti Serena , Nigri Anna , Pandolfo Massimo , Reetz Kathrin , Roberts Timothy P , Romanzetti Sandro , Rudko David A , Scaravilli Alessandra , Schulz Jörg B , Subramony S H , Timmann Dagmar , França Marcondes C , Harding Ian H , Rezende Thiago J R ,   TRACK-FA Neuroimaging Consortium
Published: June 2024

AbstractPurposeTo develop a dentate nucleus (DN) segmentation tool using deep learning (DL) applied to brain quantitative susceptibility mapping (QSM) images.Materials and MethodsBrain QSM images from 132 healthy controls and 170 individuals with cerebellar ataxia or multiple sclerosis were collected from nine different datasets worldwide for this retrospective study. Manual delineation of the DN (gray matter and white matter hilus) was first undertaken by experienced raters with a robust quality control process. Performance of automated segmentation was compared following training using several DL architectures. A two-step approach was implemented, composed of a localization model followed by DN segmentation.ResultsThe manual tracing protocol produced ground-truth data with high intra-rater (average ICC 0.906) and inter-rater reliability (average ICC 0.776). Initial DL architecture exploration indicated that the nnU-Net framework performed best. The two-step localization plus segmentation pipeline achieved a Dice score of 0.898±0.031 and 0.894±0.036 for left and right DN, respectively. In external validation, our algorithm outperformed the leading existing automated tool (left/right DN Dice 0.863±0.038/0.843±0.066 vs. 0.568±0.222/0.582±0.239). The model demonstrated generalizability across unseen datasets during the training step. The measures showed a superior correlation index with manual annotations and performed well in both isotropic and anisotropic QSM datasets.ConclusionWe provide a model that accurately and efficiently segments the DN from brain QSM images. The model can be readily deployed for use in observational, natural history, and treatment trials for biomarker discovery.
Optimal mix of differentiated service delivery models for HIV treatment in Zambia: a mathematical modelling study
Authors: Lekodeba Nkgomeleng , Rosen Sydney , Phiri Bevis , Masuku Sithabiso , Govathson Caroline , Kamanga Aniset , Haimbe Prudence , Shakwelele Hilda , Mwansa Muya , Lumano-Mulenga Priscilla , Huber Amy , Pascoe Sophie , Jamieson Lise , Nichols Brooke E 
Published: June 2024

AbstractBackgroundZambia has scaled up differentiated service delivery (DSD) models for antiretroviral treatment (ART) to provide more client-centric care and increase service delivery efficiency. The current DSD landscape includes multiple models of care based on guidelines, resources, partner inputs, and other factors. We used local data to identify cost-effective combinations of DSD models that will maximize benefits and/or minimize costs to guide future DSD expansion.MethodsWe developed a mathematical Excel-based model using retrospective retention and viral suppression data from a national cohort of ART clients (≥15 years) between January 2018-March 2022 stratified by age, sex, setting (urban/rural), and model of ART delivery. Outcomes (viral suppression and retention in care), provider costs, and costs to clients for each model were estimated from the cohort and previously-published data. For different combinations of the nine DSD models in use, we evaluated the incremental cost to the health system per additional ART client virally suppressed on treatment compared to the 2022 base case.ResultsOf the 125 combinations of DSD models evaluated, six were on the cost-effectiveness frontier (CEF): 1) six-month dispensing (6MMD)-only; 2) 6MMD and adherence groups (AGs); 3) AGs-only; 4) fast track refills (FTRs) and AGs; 5) FTRs-only; and 6) AGs and home ART delivery. 6MMD-only was cost-saving compared to the base case, increased the proportion of clients virally suppressed by 1.6%, and decreased costs to clients by 16.6%. The next two scenarios on the CEF, 6MMD+AGs and AGs-only, each cost an additional $245 per person virally suppressed, increased the total number of individuals suppressed on treatment by 2.8% and 4.8%, respectively, and increased costs to clients by 63% and 143%, respectively.ConclusionsMathematical modelling using existing data can identify cost-effective mixes of DSD models and allocations of clients to these models, while ensuring that all client sub-populations are explicitly considered. In Zambia, providing 6MMD to all eligible clients is likely to be cost-saving, while health outcomes can be improved by allocating clients to selected models based on sub-population.
The impact on clinical success from the 23andMe cohort
Authors: Wang Xin , Karagounis Sotiris , Shringarpure Suyash S. , Srivas Rohith , Su Qiaojuan Jane ,   23andMe Research Team, Vacic Vladimir , Pitts Steven J. , Auton Adam 
Published: June 2024

Abstract90% of therapeutic programs that enter clinical trials ultimately fail. Human genetic variation provides a set of “natural experiments” that can inform successful strategies for therapeutic discovery. Previous work has estimated that drug targets with human genetics supported mechanisms have a 2-3x increased likelihood of succeeding in the clinic compared to those without. 23andMe, Inc. is a direct-to-consumer genetics company that has created a human genetics dataset approximately an order of magnitude larger in sample size than current publically available cohorts. As of 2024, 23andMe has approximately 15 million individuals with genotype and phenotype data, of which ∼80% consent to participation in research. In this work, we explore how both the scale of the genetic data and improved methods to link genetic associations to putative causal genes impact the prediction of clinical success. Comparing the total number of target-indication pairs that have reached at least phase I that are also supported by genetic evidence, the number of target-indication pairs with support from 23andMe is 60% greater than that with support from all GWAS datasets in the public domain. Including 23andMe genetic evidence approximately doubles the number of target-indication pairs in the clinic that are supported by human genetics. Furthermore, we show that genetic associations derived from entirely self-reported phenotypes are 2-3x enriched for clinical success, just as for clinically derived phenotypes. In contrast to conclusions from the recent publication of Minikelet al., we found that minor allele frequencies and effect sizes from GWAS influence the relative success estimates for program approvals, and that drug programs supported by rare and large effect associations have greater (3-4x) likelihood to be approved compared to common variant associations with small effects. Finally, improved gene mapping to identify the likely causal genes underlying genetic associations can result in up to 4-5x enrichment for trial success. With the increased power and scale of the 23andMe genetic dataset, we identify an expansive set of opportunities that may be pursued in the clinic, emphasizing the importance of cohort size and gene mapping confidence in deriving clinical value.
Computational pipeline for targeted integration and variable payload expression for bacteriophage engineering
Authors: Fernbach Jonas , Hegedis Emese , Loessner Martin J. , Kilcher Samuel 
Published: June 2024

AbstractBacteriophages offer a promising alternative to conventional antimicrobial treatments, particularly in cases where such treatments have proven ineffective. While naturally occurring phages serve as viable options for phage therapy, advances in synthetic biology and genome engineering enable precise modifications to phages to enhance their therapeutic potential. One such approach is the introduction of antimicrobial genetic payloads into the phage genome. Conventional practice is to integrate such payloads behind genes expressed at very high levels late in the infection cycle, such as the major capsid gene (cps). Nevertheless, phages engineered to contain antimicrobial payloads are often difficult to obtain. For instance, the high expression of toxic payloads can prematurely halt host metabolism, leading to the failure in assembling viable phage progeny. To potentially expand the range of genes viable as genetic payloads, we developed a method to identify intergenic loci with favorable expression levels. We used the machine learning (ML)-based promoter prediction algorithm PhagePromoter to identify these loci. We then used this information to design a computationally-assisted engineering pipeline for the integration of genomic payloads at these locations. We validated our approach experimentally, engineering phages with bioluminescent reporter payloads at various predicted loci. We used the well characterized, strictly lytic,Staphylococcus aureus-infecting bacteriophage, K, as an engineering scaffold and employed homologous recombination to engineer three recombinant phages containing the reporter payload at different predicted loci throughout the genome. The recombinant phages exhibited expression levels consistent with our computational predictions and showed temporal expression patterns corresponding to their genomic locations in early, middle, or late gene clusters. Our study underscores the potential of integrating computational tools with classical sequence analysis to streamline the phage engineering process. This approach not only facilitates the rational design of phages with targeted payload insertions but also paves the way for high-throughput, automated phage engineering, fostering a new era of personalized phage therapy.
How the brain learns to parse images using an attentional, incremental grouping process
Authors: Mollard Sami , Bohte Sander M. , Roelfsema Pieter R. 
Published: June 2024

AbstractNatural scenes usually contain a vast number of objects that need to be segmented and segregated from each other and from the background to guide behaviour. In the visual brain, object-based attention is the process by which image fragments belonging to the same objects are grouped together. The curve-tracing task is a special case of a perceptual grouping task that tests our ability to group image elements of an elongated curve. The task consists in determining which image elements belong to the same curve, and in the brain, neurons spread an enhanced activity level over the representation of the relevant curve. A previous “growth-cone model of attention” accounted for the scale invariance of tracing by proposing that the enhanced activity propagates at multiple levels of the visual cortical hierarchy. However, the precise neuronal circuitry for learning and implementing scale-invariant tracing remains unknown. We propose a new recurrent architecture for the scale-invariant labelling of curves and objects. The architecture is composed of a feedforward pathway that dynamically selects the right scale and prevents the spilling over of the enhanced activity to other curves, and a recurrent pathway for tag spreading that involves horizontal and feedback interactions, mediated by a disinhibitory loop involving VIP and SOM interneurons. We trained the network with curves up to seven pixels long using reinforcement learning and a learning rule local in time and space and we found that it generalized to curves of any length and to spatially extended objects. The network chose the appropriate scale and switched to higher or lower scales as dictated by the distance between curves, just has as been observed in human psychophysics and in the visual cortex of monkeys. Our work provide a mechanistic account of the learning of scale-invariant perceptual grouping in the brain.Significance StatementObjects are labelled and grouped in the visual cortex via a tag of enhanced activity. If the scale-invariant dynamics of propagations of this tag are well characterised, it remains unknown what neural architectures and learning rules can produce those dynamics. This work is the first to propose a neural architecture trained with reward that give rises to the same dynamics observed in monkeys’ visual cortex or human reaction times, shedding light on the mechanisms of multiscale object-based attention in the visual cortex.