bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing Avoidable Transfer Delays in the Pediatric Intensive Care Unit for Status Asthmaticus Patients
Authors: Karube Takaharu , Goins Theresa , Karsies Todd J. , Gee Samantha W. 
Published: January 2022

Introduction:
Status asthmaticus (acute severe asthma) is one of the most common reasons for Pediatric Intensive Care Unit (PICU) admission. Accordingly, ensuring optimal throughput for patients admitted with status asthmaticus is essential for optimizing PICU capacity. Few studies specifically address effective methods to reduce delays related to PICU discharge. This project aimed to identify and reduce avoidable delays in PICU discharge for status asthmaticus patients.

Methods:
This quality improvement project focused on reducing transfer delays for status asthmaticus patients admitted to the PICU at a freestanding academic children’s hospital. We standardized the transfer criteria, identified barriers to an efficient transfer, and implemented multidisciplinary interventions. The primary aim was to decrease the average duration from fulfilling the transfer criteria to PICU discharge by 15% from the baseline within 8 months of implementation. The balancing measure was readmissions to the PICU for asthma exacerbations within 24 hours from PICU discharge.

Results:
The analysis included 623 patients. Following interventions, the time from fulfilling transfer criteria to PICU discharge decreased from 9.8 hours to 6.8 hours, a 30.6% reduction from baseline. Improvements were sustained for 6 months. In the preintervention group, three patients were readmitted to the PICU within 24 hours of transferring out of the PICU, but no patient was readmitted during the postintervention period.

Conclusions:
Standardizing transfer criteria and implementing multidisciplinary strategies can reduce avoidable PICU discharge delays for patients with status asthmaticus. The application of a similar approach could potentially reduce avoidable delays for other conditions in the PICU.
Improving Quality and Efficiency in Pediatric Emergency Department Behavioral Health Care
Authors: Emerson Beth L. , Setzer Erika , Blake Eileen , Siew Lawrence 
Published: January 2022

Introduction:
Many children with behavioral health concerns increasingly utilize the emergency department for assessment and care. These visits are increasing in frequency, length, and cost, further stressing already limited resources. To improve the quality of care in this population, we developed a multidisciplinary improvement initiative to decrease the length of stay by 10% (from 5.2 hours), increase suicide screening to 90%, and improve patient and family experience by 10% (from 89.7).

Methods:
We leveraged a multidisciplinary team to map care processes, standardize suicide risk screening, optimize staffing, and develop a brochure to demystify patients’ and families’ visits. We developed dashboards and a call-back system following discharge to understand engagement in post-acute care plans. We utilized run charts to identify signals of nonrandom variation.

Results:
We reduced overall length of stay from 5.2 to 4 hours, improved patient experience scores from 89.7 to 93.2, and increased the suicidality screening rate from 0% to 94%. There was no change in the 72-hour return rate in this population.

Conclusions:
Engagement of a multidisciplinary team, with strategic implementation of improvements, measurably improved many aspects of care for pediatric patients with behavioral health crises in the emergency department setting. Recidivism, however, remains unchanged in this population and continues as a goal for future work.
In Vitro and In Vivo Pathogenicity of A. alternata to Sugar beet and Assessment of Sensitivity to Fungicides
Authors: Haque Md Ehsanul , Parvin Most Shanaj 
Published: January 2022

AbstractA. alternata is a weak and opportunistic pathogen, but recently this pathogen has been reported in major sugar beet growing regions in the US. Therefore, we were interested to investigate the in-vitro and in-vivo pathogenesis of A. alternata to sugar beet seed, seedlings, tissue slices, stecklings, and roots. The in-vitro study demonstrated that A. alternata reduces seed germination, causes damping-off of seedlings, and decomposes beet tissue. The in-vivo study showed the same inoculum responsible for Alternaria leaf spots, and black circular spots on beetroot. Furthermore, we did a preliminary study to determine in vitro sensitivities of some fungicides to determine the effective concentration that inhibited 50% of radial mycelial growth (EC50 values) of A. alternata. The results indicated that EC50 values ranged from 0.0023 to 0.0058 for PROLINE, from 0.0004 to 0.0021 for OMEGA, and from 0.0027 to 0.0053 for Super TIN. Among the potential fungicides, the efficiency of quinone outside inhibitors (QoI- PRIAXOR) was relatively higher to inhibit the radial growth of A. alternata, irrespective of concentrations.
A Phase 2 open-label study to determine the safety and efficacy of weekly dosing of ATL1102 in patients with non-ambulatory Duchenne muscular dystrophy
Authors: Woodcock IR , Tachas G , Desem N , Houweling PJ , Yiu EM , Kean M , Emmanuel J , Kennedy R , Carroll K , de Valle K , Adams J , Lamandé SR , Coles C , Tiong C , Villano D , Button P , Hogrel J-Y , Catling-Seyffer S , Delatycki MB , Ryan MM ,   ATL1102 in DMD clinical trial group
Published: January 2022

AbstractBackgroundATL1102 is a 2’MOE gapmer antisense oligonucleotide to the CD49d alpha subunit of VLA-4. ATL1102 inhibits expression of CD49d on lymphocytes, thereby reducing their survival, activation and migration to sites of inflammation. Children with Duchenne muscular dystrophy (DMD) have dystrophin deficient muscles. These are susceptible to contraction induced injury which triggers the immune system, exacerbating muscle damage. CD49d is a biomarker of disease severity in DMD, with increased numbers of high CD49d expressing T cells correlating with more severe and progressive weakess, despite corticosteroid treatment.MethodsThis Phase 2 open label study assessed the safety, efficacy and pharmacokinetic profile of ATL1102 administered as 25 mg weekly by subcutaneous injection for 24 weeks in 9 non-ambulatory boys with DMD aged 10–18 years. Participants receiving corticosteroid therapy were allowed into the study if on a stable dose for at least 3 months. The main objective was to assess safety and tolerability of ATL1102. Secondary objectives included the effect of ATL1102 on lymphocyte numbers in the blood, functional changes in upper limb function as assessed by Performance of Upper Limb test (PUL 2.0) and upper limb strength using MyoGrip and MyoPinch compared to baseline.ResultsATL1102 was generally safe and well tolerated. No serious adverse events were reported. There were no participant withdrawals from the study. The most commonly reported adverse events were injection site erythema and skin discoloration. There was no statistically significant change in lymphocyte count from baseline to week eight (mean change -0.56×109/L 95%CI -1.52, 0.40), week twelve (mean change -0.53×109/L 95%CI -1.65, 0.58) or week twenty-four (mean change -0.28×109/L 95%CI -1.10, 0.55) of dosing however, the CD3+CD49d+ T lymphocytes were statistically significantly higher at week 28 compared to week 24, four weeks past the last dose (mean change 0.40×109/L 95%CI 0.05, 0.74; p=0.030). Functional muscle strength, as measured by the PUL2.0, EK2 and Myoset grip and pinch measures, and MRI fat fraction of the forearm muscles were stable throughout the trial period.ConclusionATL1102, a novel antisense drug being developed for the treatment of inflammation that exacerbates muscle fibre damage in DMD, appears to be safe and well tolerated in non-ambulant boys with DMD. The apparent stabilisation observed on multiple muscle disease progression parameters assessed over the study duration support the continued development of ATL1102 for the treatment of DMD.
Association between oral health and hyperuricemia in Korean adults: Korea National Health and Nutrition Examination Survey 2016-2019
Authors: Park Junyong , son Minkook , Lee Sung Won , Chung Won Tae , Lee Sang Yeob 
Published: January 2022

AbstractHyperuricemia plays an essential role in the development of gout. Despite the clinical importance of hyperuricemia, a direct relationship between oral health and hyperuricemia has not been established. Therefore, we aim to investigate the association between oral health and hyperuricemia in Korean adults.We selected 17,584 subjects from the Korea National Health and Nutrition Examination Survey 2016–2019 database. Oral health-related variables included the number of dental caries, regular tooth brushing, use of secondary oral products, and regular dental examination. The odds ratio (OR) and 95% confidence intervals (CIs) for hyperuricemia were calculated using a multivariable-adjusted logistic regression model.In all subjects, oral health status with dental caries and oral health behaviors, including tooth brushing; secondary oral products; and regular dental examination, were significantly associated with hyperuricemia. The adjusted OR and 95% CIs for hyperuricemia comparing more than three dental caries with no dental caries were 1.28 (1.08–1.51). The adjusted OR and 95% CIs for hyperuricemia in regular tooth brushing, use of secondary oral products, and regular dental examination were 0.78 (0.67–0.91), 0.91 (0.82–1.00), and 0.86 (0.78–0.95), respectively. Notably, the association between oral health and hyperuricemia was more prominent in male subjects. In addition, when subjects were grouped by the scoring system regarding oral health, the prevalence of hyperuricemia was lower in groups with a better oral health score.In conclusion, we demonstrated that oral health status and behaviors were associated with hyperuricemia, especially in males. Further complementary studies are needed to confirm the definite association between oral health and hyperuricemia.
Discrepancy review: A feasibility study of a novel peer review intervention to reduce undisclosed discrepancies between registrations and publications
Authors:   TARG Meta-Research Group & Collaborators, Thibault Robert T. , Hardwicke Tom E. , Clark Robbie W. A. , Pennington Charlotte R. , Nilsonne Gustav , O'Mahony Aoife , Drax Katie , Thompson Jacqueline , Munafò Marcus R. 
Published: January 2022

AbstractBackgroundUndisclosed discrepancies often exist between study registrations and their associated publications. Discrepancies can increase risk of bias, and when undisclosed, they disguise this increased risk of bias from readers. To remedy this issue, we developed an intervention called discrepancy review. We provided journals with peer reviewers specifically assigned to check for undisclosed discrepancies between registrations and manuscripts submitted to journals.ObjectivesWe aimed to (1) evaluate the feasibility of incorporating discrepancy review as a regular practice at scientific journals and the feasibility of conducting a trial on discrepancy review; (2) explore the benefits and time required to incorporate discrepancy review as a regular practice at scientific journals; and (3) refine the discrepancy review process.MethodWe performed discrepancy review on 18 manuscripts submitted to Nicotine and Tobacco Research and 3 manuscripts submitted to the European Journal of Personality. We iteratively refined the discrepancy review process based on feedback from discrepancy reviewers, editors, and authors. We then assessed whether revised manuscripts addressed recommendations from discrepancy reviewers and identified potential outcome measures for use in a future trial of discrepancy review.ResultsRegistrations were generally too imprecise to be effectively evaluated by our original discrepancy review process so we developed a simplified, semi-structured process. Authors addressed the majority of discrepancy reviewer comments and there was no opposition to running a trial from authors, editors, or discrepancy reviewers. Clinical trial registrations were more precise but less comprehensive than registrations on the Open Science Framework, suggesting they should be evaluated in separate trials. Outcome measures for a trial of discrepancy review on clinical trial registration could include the presence of primary or secondary outcome discrepancies and whether publications that are not the primary report from a clinical trial registration are clearly described as such. Outcome measures for a trial on Open Science Framework registrations could include assessments of whether registrations are permanent, as well as an overarching subjective assessment of the impact of discrepancies.ConclusionWe found that discrepancy review could feasibly be introduced as a regular practice at journals interested in this process. A full trial of discrepancy review would be needed to evaluate its impact on reducing undisclosed discrepancies.
Phenotypic Pliancy and the Breakdown of Epigenetic Polycomb Mechanisms
Authors: Lambros Maryl , Sella Yehonatan , Bergman Aviv 
Published: January 2022

AbstractEpigenetic regulatory mechanisms allow multicellular organisms to develop distinct specialized cell identities despite having the same total genome. Cell-fate choices are based on gene expression programs and environmental cues that cells experience during embryonic development, and are usually maintained throughout the life of the organism despite new environmental cues. The evolutionarily conserved Polycomb group (PcG) proteins form Polycomb Repressive Complexes that help orchestrate these developmental choices. Post-development, these complexes actively maintain the resulting cell fate, even in the face of environmental perturbations. Given the crucial role of these polycomb mechanisms in providing phenotypic fidelity (i.e. maintenance of cell fate), we hypothesize that their dysregulation after development will lead to decreased phenotypic fidelity allowing dysregulated cells to sustainably switch their phenotype in response to environmental changes. We call this abnormal phenotypic switchingphenotypic pliancy. We introduce a general computational evolutionary model that allows us to test our systems-level phenotypic pliancy hypothesisin-silicoand in a context-independent manner. We find that 1) phenotypic fidelity is an emergent systems-level property of PcG-like mechanism evolution, and 2) phenotypic pliancy is an emergent systems-level property resulting from this mechanism’s dysregulation. Since there is evidence that metastatic cells behave in a phenotypically pliant manner, we hypothesize that progression to metastasis is driven by the emergence of phenotypic pliancy in cancer cells as a result of PcG mechanism dysregulation. We corroborate our hypothesis using single-cell RNA-sequencing data from metastatic cancers. We find that metastatic cancer cells are phenotypically pliant in the same manner as predicted by our model.Significance StatementWe introduce the concept of cellular phenotypic pliancy– sustained abnormal phenotypic switching in response to environmental changes– and demonstrate that such behavior can be caused by dysregulation of Polycomb mechanisms. To overcome the incomplete knowledge about these mechanisms in higher organisms, we develop an abstract computational model to study the emergence of phenotypic pliancy from a general systems-level view by confirming our hypothesis over a wide range of simulated gene-regulatory networks and Polycomb mechanism patterns. We corroborate our hypothesis and model predictions using single-cell RNA-seq metastatic cancer datasets. Our hypothesis has the potential to shed light on a general phenomenon for complex diseases where abnormal phenotypic switching is relevant.
Interplay between murine sex-biased gene expression and hepatic zonation revealed by single nucleus RNA sequencing
Authors: Goldfarb Christine N. , Karri Kritika , Pyatkov Maxim , Waxman David J. 
Published: January 2022

AbstractThe zonation of liver metabolic processes is well-characterized; however, little is known about the cell type-specificity and zonation of sexually dimorphic gene expression or its growth hormone (GH)-dependent transcriptional regulators. We address these issues using single nucleus RNA sequencing of 32,000 nuclei representing nine major liver cell types. Nuclei were extracted from livers from young adult male and female mice, from male mice infused with GH continuously to mimic the female plasma GH pattern, and from mice treated with TCPOBOP, a xenobiotic agonist ligand of the liver nuclear receptor CAR (Nr1i3). Analysis of these rich transcriptomic datasets revealed: 1) expression of sex-biased genes and their key GH-dependent transcriptional regulators is primarily restricted to hepatocytes and is not a feature of liver non-parenchymal cells; 2) many sex-biased transcripts show sex-dependent zonation within the liver lobule; 3) gene expression is substantially feminized in both periportal and pericentral hepatocytes when male mice are infused with GH continuously; 4) sequencing nuclei increases the sensitivity for detecting thousands of nuclear-enriched lncRNAs and enables determination of their liver cell type-specificity, sex bias and hepatocyte zonation profiles; 5) the periportal to pericentral hepatocyte cell ratio is significantly higher in male than female liver; and 6) TCPOBOP exposure disrupts sex-specific gene expression and hepatocyte zonation within the liver lobule. These findings highlight the complex interconnections between hepatic sexual dimorphism and zonation at the single cell level and reveal how endogenous hormones and foreign chemical exposure can alter these interactions across the liver lobule with large effects on both protein-coding genes and lncRNAs.SynopsisSingle nucleus RNA-seq analysis elucidated the cell type-specificity and zonation of the sex-biased murine liver transcriptome, including thousands of long non-coding RNAs. Xenobiotic exposure induced widespread dysregulation, including both gain and loss of sex-biased gene expression and changes in zonation.
Redefining the architecture of ferlin proteins: insights into multi-domain protein structure and function
Authors: Dominguez Matthew J. , McCord Jon J. , Sutton R. Bryan 
Published: January 2022

AbstractFerlins are complex, multidomain proteins whose functions involve membrane fusion, membrane repair, and exocytosis. Progress in studying the domain composition of ferlins has been problematic due to the large size of the ferlin proteins and the difficulty in computing accurate residue ranges for each respective ferlin protein domain. However, recent advances in in silico protein folding methods have significantly enhanced the understanding of the domain structure of these complex proteins. To compute unbiased domain boundaries, we used RoseTTAFold to assemble full-length models for each of the six human ferlin proteins (dysferlin, myoferlin, otoferlin, Fer1L4, Fer1L5, and Fer1L6). Despite the differences in amino acid sequence between the ferlin proteins, the domain ranges and the distinct subdomains in some of the ferlin domains were remarkably consistent. Further, the RoseTTAFold/AlphaFold2 in silico boundary prediction methods allowed us to describe and characterize a previously unknown C2 domain, ubiquitous in all human ferlins, which we refer to as C2-FerA. At present, the ferlin domain-domain interactions implied by the full-length in silico models are predicted to have a low accuracy; however, the use of RoseTTAFold and AlphaFold2 as a domain finder has proven to be a powerful research tool in understanding ferlin structure.
Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography: First-in-human study
Authors: Wang Jeffrey B. , Bruss Joel E. , Oya Hiroyuki , Uitermarkt Brandt D. , Trapp Nicholas T. , Gander Phillip E. , Howard Matthew A. , Keller Corey J. , Boes Aaron D. 
Published: January 2022

AbstractTranscranial magnetic stimulation (TMS) is increasingly used as a noninvasive technique for neuromodulation in research and clinical applications, yet its mechanisms are not well understood. Here, we present the first in-human study evaluating the effects of TMS using intracranial electrocorticography (iEEG) in neurosurgical patients. We first evaluated safety in a gel-based phantom. We then performed TMS-iEEG in 20 neurosurgical participants with no adverse events. Next, we evaluated brain-wide intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N=10, 1414 electrodes). We demonstrate that TMS preferentially induces neuronal responses locally within the dlPFC at sites with higher electric field strength. Evoked responses were also noted downstream in the anterior cingulate and anterior insular cortex, regions functionally connected to the dlPFC. These findings support the safety and promise of TMS-iEEG in humans to examine local and network-level effects of TMS with higher spatiotemporal resolution than currently available methods.
Close kin dyads indicate intergenerational dispersal and barriers
Authors: Schmidt Thomas L , Elfekih Samia , Cao Li-Jun , Wei Shu-Jun , Al-Fageeh Mohamed B , Nassar Majed , Al-Malik Abdulaziz , Hoffmann Ary A 
Published: January 2022

AbstractThe movement of individuals through continuous space is typically constrained by dispersal ability and dispersal barriers. A range of approaches have been developed to investigate these. Kindisperseis a new approach that infers intergenerational dispersal (σ) from close kin dyads, and appears particularly useful for investigating taxa that are difficult to observe individually. This study, focusing on the mosquitoAedes aegypti, shows how the same close kin data can also be used for barrier detection. We empirically demonstrate this new extension of the method using genome-wide sequence data from 266Ae. aegypti. First, we use the spatial distribution of full-sib dyads collected within one generation to infer past movements of ovipositing female mosquitoes. These dyads indicated the relative barrier strengths of two roads, and performed favourably against alternative genetic methods for detecting barriers. The difference in variance between the sib and first cousin spatial distributions was used to infer movement over the past two generations, providing estimates of intergenerational dispersal (σ = 81.5-197.1 m.gen-1/2) and density (ρ = 833-4864 km-2). Dispersal estimates showed general agreement with those from mark-release-recapture studies. Barriers, σ, ρ, and neighbourhood size (331-526) can inform forthcoming releases of dengue-suppressingWolbachiabacteria into this mosquito population.