bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Parental Perspectives and Concerns about Pediatric Cochlear Implantation: A Social Media Analysis
Authors: Huang Emily Y. , Hairston Tai K. , Walsh Jonathan , Ballard Megan E. , Boss Emily F. , Jenks Carolyn M. 
Published: September 2023

Objective
Parents often experience uncertainty during decision-making for their child’s cochlear implantation (CI) surgery, and online forums provide insight on parental opinions that might not be expressed in clinic. This study aims to evaluate parental perspectives and concerns about pediatric CI using social media analysis.

Study Design
Qualitative study.

Setting
Three online forums involving parental posts about pediatric CI.

Intervention/Methods
Forums were queried using keywords (e.g., “cochlear implant”) to gather all U.S. parent-initiated posts about pediatric CI from 2006 to 2021. Thematic content analysis was performed to classify posts by overarching domain, themes, and subthemes. Posts were reviewed for thematic synthesis and double coded. Descriptive statistics were calculated for each theme by unique users.

Results
A total of 79 posts by 41 unique users were analyzed. Themes relating to decision for CI included facilitators, inhibitors, resources, and feelings. Parents posted about lack of benefit from hearing aids promoting decision for CI and high cost as an inhibitor. Some expressed concern about making a major decision for a minor. Parents often mentioned their child’s healthcare providers and social media as resources.

Conclusion
Through social media posts, parental priorities and concerns for decision-making of CI surgery were identified. Findings may guide discussions between physicians and parents and facilitate shared decision-making about CI.
Improving Documentation of Pain Reassessment after Pain Management Interventions in the NICU
Authors: Israel Smitha , Perazzo Sofia , Lee Morgan , Samson Rachel , Safari-Ferra Parissa , Badh Ranjodh , Abera Solomon , Soghier Lamia 
Published: September 2023

Background:Neonates exposed to painful procedures require pain assessment and reassessment using nonverbal scales. Nurses perform initial assessments routinely, but reassessment is variable. The goal was to increase pain reassessments in neonates with a previous score of 4 or higher within 60 minutes from 50% to 75% within 12 months.Methods:After identifying key drivers, we tested several interventions using the IHI’s Model for Improvement. The outcome measure was the rate of reassessments within 1 hour after scoring ≥4 on the Neonatal Pain Agitation and Sedation Scale (N-PASS). Duration of time between scoring and intervention was documented. Interventions included electronic health record (EHR) changes, direct communication with bedside nurses through text messages and emails, in-person education, and a yearly competency module. The process measure was the number of messages/emails to staff. Sedation scores were the balancing measure.Results:Baseline compliance was 50% with significant variability. A centerline shift occurred after the first intervention. After the first four interventions in the following 3 months, a 29% total increase occurred. Overall time-lapse between reassessments decreased from 102 to 90 minutes. Overall sedation scores decreased from -2.5 during the baseline to -1.7 during the sustain period. The goal of 75% pain reassessments was achieved and sustained for two years.Conclusions:Automated tools such as the trigger report provided data that increased noncompliance visibility. Real-time and personalized reminders and education improved awareness and set the tone for culture change. Electronic health record reminders for reassessments and standardized annual education helped in sustaining change.
Firearm Safety Screening in the Pediatric Hospital Setting: A Quality Improvement Initiative
Authors: Oddo Elizabeth R. , Kumar Neha , Andrews Annie L. , Kwon Stephanie 
Published: September 2023

Background:
Firearm injuries are a leading cause of morbidity and mortality for US youth. Secure storage is protective against firearm injuries in children. Despite this evidence and national recommendations, rates of firearm safety screening among pediatric providers are low, particularly in the inpatient setting. Therefore, we aimed to increase the frequency of firearm safety screening among patients admitted to the Pediatric Hospital Medicine service.

Methods:
This project occurred in a tertiary pediatric hospital with a medium-sized pediatric residency program. The initial intervention was a firearm safety screening tool embedded into the electronic health record history and physical note template. Subsequent interventions included nursing education, monthly reminder emails, and gun violence discussions during intern orientation. Patients who screened positive were provided with educational materials and a free gun lock. Data collection occurred by chart review to determine the frequency of screening documentation in the H&P. A survey was also conducted among pediatric residents to identify persistent barriers to screening.

Results:
The percentage of inpatient firearm safety screening increased from 0.01% to 39% over 25 months, with a centerline shift noted after 2 months. Residents cited a lack of time with the patient and a belief that it was not the appropriate time to screen as persistent barriers to screening.

Conclusions:
This study identified an effective approach to improving firearm safety screening in an academic pediatric hospital. Hospitalization represents a unique opportunity for firearm safety screening and counseling, and inpatient providers should feel empowered to intervene in this setting.
Microevolution of clade II isolates ofCandida aurishighlights multifaceted intra-clade heterogeneity in acquiring resistance towards amphotericin B
Authors: Chauhan Anshu , Kumar Praveen , Kumar Mohit , Narayanan Aswathy , Yadav Kusum , Ali Basharat , Saini Amandeep , Singh Ashutosh , Banerjee Atanu , Rudramurthy Shivaprakash M. , Chakrabarti Arunaloke , Mondal Alok K. , Gaur Naseem A. , Sanyal Kaustuv , Prasad Rajendra 
Published: September 2023

AbstractCandida aurisexhibits high-level resistance to amphotericin B (AmB). Mechanisms such as ergosterol biosynthesis malfunction, oxidative damage mismanagement, and increased drug efflux contribute to AmB resistance inC. auris. In this study, we experimentally evolved two East Asian drug-susceptible clade II isolates ofC. auris(P2428 and CBS10913T) isolated from different geographical locations to develop resistance against AmB. We analysed alterations in karyotype, genome sequence, and gene expression profiles to uncover the mechanisms driving AmB resistance. The independently evolved clade II adaptors displayed up to 4-16-fold higher MIC50, as compared to the parental cells.AOX2(alternative oxidase) and the cell wall integrity pathway have been identified as critical in the development of AmB resistance. However, we noted certain intra-clade heterogeneity in the associated mechanisms. While in P2428 adaptors (P-lines), the ergosterol and sphingolipid pathways appear to play a crucial role, this was not the case for CBS10913Tadaptors (A-lines), which acquired resistance independent of lipid-associated changes. The transcriptomic, WGS, and phenotypic analyses also confirm that the evolved AmB-resistant isolates follow distinct trajectories for adaptation, Furthermore, unlike the fluconazole-resistant isolates, as reported previously, changes in ploidy do not seem to contribute to the differential mechanisms of AmB resistance. Overall, this study not only provides insights into the mechanisms and pathways involved in AmB resistance but also highlights intra-clade-heterogeneity that exists within clade II ofC. auris.ImportanceCandida aurisdemonstrates significant resistance to amphotericin B (AmB) that stems from factors like alteration of ergosterol biosynthesis, perturbation of the oxidative damage response, etc. A comprehensive understanding of underlying mechanisms can be studied in a holistic manner by subjecting resistant as well as susceptible clinical isolates to a comparative genome-level analysis. An alternate and more dynamic approach is to expose susceptible isolates to a certain concentration of drug which is not lethal but can trigger the resistance mechanisms. In the present study, we evolvedC. auristowards AmB and observed novel and differential mechanisms of resistance development, in two different isolates despite belonging to the same clade. This study provides insights into the intra-clade heterogeneous behavior ofC. auristowards AmB.
Reduction in myocardial fibrosis in MDX mice on oral consumption ofAureobasidium Pullulansproduced Neu REFIX Beta-glucans; holds potential as an adjuvant in managing post-transplantation organ fibrosis
Authors: Preethy Senthilkumar , Yamamoto Naoki , Cherian Kottoorathu Mammen , Premsekar Rajasekaran , Levy Gary A , Senthilkumar Rajappa , Abraham Samuel JK 
Published: September 2023

AbstractOrgan fibrosis is one of the major causes of morbidity and mortality globally. Though fibrosis in genetic diseases such as Duchenne muscular dystrophy (DMD) may be attributed to the genetic defect, chronic microinflammation remains a key mechanism underlying such fibrosis, which also precedes both other organ fibrosis and post-organ transplant fibrosis. Having proven the anti-inflammatory, anti-fibrotic effects of Beta-1,3-1,6-glucan (Neu-REFIX) produced by N-163 strain ofAureobasidium Pullulansin earlier clinical and pre-clinical studies, we performed the current study to evaluate its effects on myocardial fibrosis. N-163 beta-glucan was administered to 45 mice in three groups, each fifteen animals, Gr. 1, normal mice, Gr.2, mdx mice as vehicle, Gr.3, mdx mice which were administered Neu REFIX beta-glucan orally. Evaluation of Collagen Type I (Col-I) in myocardium was performed by immunohistochemistry. Percentage of myocardium Col-I positive area of 6.42 ± 2.67 significantly decreased in the Neu-REFIX group (4.32 ± 1.78) (p-value < 0.01). As myocardial fibrosis has been shown to be reduced following treatment with N-163 beta glucan in a genetic, muscle structure anomaly disease such as DMD, in addition to adding value to DMD patients, in whom myocardial failure occurs in the advanced stages leading to pre-mature death, Neu-REFIX beta-glucan adjuvant treatment in the setting of solid organ transplantation may be of value to reduce the incidence of fibrosis which is a known feature of chronic allograft rejection leading to graft loss.
Distinct transcriptional profiles of maternal and fetal placental macrophages at term are associated with gravidity
Authors: Ozarslan Nida , Robinson Joshua F. , Buarpung Sirirak , Kim M. Yvonne , Ansbro Megan R. , Akram Jason , Montoya Dennis J. , Kamya Moses R. , Kakuru Abel , Dorsey Grant , Rosenthal Philip J. , Cheng Genhong , Feeney Margaret E. , Fisher Susan J. , Gaw Stephanie L. 
Published: September 2023

AbstractMaternal intervillous monocytes (MIMs) and fetal Hofbauer cells (HBCs) are myeloid-derived immune cells at the maternal-fetal interface. Little is known regarding the molecular phenotypes and roles of these distinct monocyte/macrophage populations. Here, we used RNA sequencing to investigate the transcriptional profiles of MIMs and HBCs in six normal term pregnancies. Our analyses revealed distinct transcriptomes of MIMs and HBCs. Genes involved in differentiation and cell organization pathways were more highly expressed in MIMs vs. HBCs. In contrast, HBCs had higher expression of genes involved in inflammatory responses and cell surface receptor signaling. Maternal gravidity influenced monocyte programming, as expression of pro-inflammatory molecules was significantly higher in MIMs from multigravidas compared to primigravidas. In HBCs, multigravidas displayed enrichment of gene pathways involved in cell-cell signaling and differentiation. In summary, our results demonstrated that MIMs and HBCs have highly divergent transcriptional signatures, reflecting their distinct origins, locations, functions, and roles in inflammatory responses. Our data further suggested that maternal gravidity influences the gene signatures of MIMs and HBCs, potentially modulating the interplay between tolerance and trained immunity. The phenomenon of reproductive immune memory may play a novel role in the differential susceptibility of primigravidas to pregnancy complications.
Mixed Multi-Level Visual, Reward, and Motor Signals in Dorsomedial Frontal Cortex Area F7 during Active Naturalistic Video Exploration
Authors: Aboharb Farid , Serene Stephen , Sliwa Julia , Freiwald Winrich 
Published: September 2023

AbstractIn the primate brain the frontal lobes support complex functions, including social cognition. Understanding the functional organization of these regions requires an approach for rich functional characterization. Here we used a novel paradigm, the visual exploration of dynamic social and non-social video scenes, to characterize diverse functions in area F7 of dorsomedial premotor cortex in the macaque monkey (Macaca mulatta) previously suggested to be involved in the representation of social interactions. We found that neural populations within this area carry information about both visual events in the videos, like head turning, and higher-level social categories, like grooming. In addition to signaling visual events, the population also encoded the delivery of juice reward. Our novel free viewing paradigm and naturalistic stimuli elicited active visual exploration, and we found that a large fraction of F7 neurons responded to the subject’s own saccadic eye movements. Information from these three different domains were not separated across distinct neural sub-populations, but distributed, such that many neurons carried sensory, reward, and motor information in a mixed format. Thus we uncover a hitherto unappreciated diversity of functions in region F7 within dorsomedial frontal cortex.
Larval brooding damselfishes and shifting body proportions: does pelagic larval swimming constrain reef fish morphology?
Authors: Lyons J.P. , Kavanagh K.D. 
Published: September 2023

AbstractThe vast majority of reef fishes, including damselfishes, have a pelagic larval stage that ends when any surviving larvae swim to a reef to settle. An extremely rare alternative lifestyle is ‘larval brooding’, where both parents protect larvae on the reef for months until they disperse nearby. The monophyletic clade of larval brooders includes two generaAcanthochromisandAltrichthys. In examination of the skeletons of these damselfishes, we found that all species of damselfish that brood larvae on the reef have a uniquely increased precaudal vertebral count, while all typical damselfishes have an invariable vertebral count with a greater proportion of caudal vertebrae. To explore the significance of the vertebral differences, we measured body proportions of larval brooders vs relatives with the typical pelagic larval stage. We found increased body cavity area and reduced muscle area in the larval brooderAcanthochromis polyacanthus. Furthermore, populations ofAcanthochromisthroughout its range have evolved significantly different proportions. In a comparison of known larval swimming ability among reef fishes, the larval brooders performed most poorly. We propose that when larval brooding evolved, relaxed selection on larval swimming performance allowed a shift in body proportions to favor a larger body cavity and altered axial patterning. Enlarged body cavity gives a fitness advantage as females could hold more of the large eggs and increase clutch size.
Activation of the aryl hydrocarbon receptor inhibits neuropilin-1 upregulation on IL-2 responding CD4+T cells
Authors: Sandoval Simone , Malany Keegan , Thongphanh Krista , Martinez Clarisa A. , Goodson Michael L. , Souza Felipe Da Costa , Lin Lo-Wei , Pennington Jamie , Lein Pamela J. , Kerkvliet Nancy I. , Ehrlich Allison K. 
Published: September 2023

AbstractNeuropilin-1 (Nrp1), a transmembrane protein expressed on CD4+T cells, is mostly studied in the context of regulatory T cell (Treg) function. More recently, there is increasing evidence that Nrp1 is also highly expressed on activated effector T cells and that increases in these Nrp1-expressing CD4+T cells correspond with immunopathology across several T cell-dependent disease models. Thus, Nrp1 may be implicated in the identification and function of immunopathologic T cells. Nrp1 downregulation in CD4+T cells is one of the strongest transcriptional changes in response to immunoregulatory compounds that act though the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. To better understand the link between AhR and Nrp1 expression on CD4+T cells, Nrp1 expression was assessedin vivoandin vitrofollowing AhR ligand treatment. In the current study, we identified that the percentage of Nrp1 expressing CD4+T cells increases over the course of activation and proliferationin vivo. The actively dividing Nrp1+Foxp3-cells express the classic effector phenotype of CD44hiCD45RBlo, and the increase in Nrp1+Foxp3-cells is prevented by AhR activation. In contrast, Nrp1 expression is not modulated by AhR activation in non-proliferating CD4+T cells. The downregulation of Nrp1 on CD4+T cells was recapitulatedin vitroin cells isolated from C57BL/6 and NOD (non-obese diabetic) mice. CD4+Foxp3-cells expressing CD25, stimulated with IL-2, or differentiated into Th1 cells, were particularly sensitive to AhR-mediated inhibition of Nrp1 upregulation. IL-2 was necessary for AhR-dependent downregulation of Nrp1 expression bothin vitroandin vivo. Collectively, the data demonstrate that Nrp1 is a CD4+T cell activation marker and that regulation of Nrp1 could be a previously undescribed mechanism by which AhR ligands modulate effector CD4+T cell responses.
Neural circuit mechanisms underlying context-specific halting inDrosophila
Authors: Sapkal Neha , Mancini Nino , Kumar Divya Sthanu , Spiller Nico , Murakami Kazuma , Vitelli Gianna , Bargeron Benjamin , Maier Kate , Eichler Katharina , Jefferis Gregory S.X.E. , Shiu Philip K. , Sterne Gabriella R. , Bidaye Salil S. 
Published: September 2023

AbstractWalking is a complex motor program involving coordinated and distributed activity across the brain and the spinal cord. Halting appropriately at the correct time is a critical but often overlooked component of walking control. While recent studies have delineated specific genetically defined neuronal populations in the mouse brainstem that drive different types of halting1–3, the underlying neural circuit mechanisms responsible for overruling the competing walking-state neural activity to generate context-appropriate halting, remain unclear. Here, we elucidate two fundamental mechanisms by whichDrosophilaimplement context-appropriate halting. The first mechanism (“walk-OFF” mechanism) relies on GABAergic neurons that inhibit specific descending walking commands in the brain, while the second mechanism (“brake” mechanism) relies on excitatory cholinergic neurons in the nerve-cord that lead to an active arrest of stepping movements. Using connectome-informed models4–6and functional studies, we show that two neuronal types that deploy the “walk-OFF” mechanism inhibit distinct populations of walking-promotion neurons, leading to differential halting of forward-walking or steering. The “brake” neurons on the other hand, override all walking commands by simultaneously inhibiting descending walking promoting pathways and increasing the resistance at the leg-joints leading to an arrest of leg movements in the stance phase of walking. We characterized two ethologically relevant behavioral contexts in which the distinct halting mechanisms were used by the animal in a mutually exclusive manner: the “walk-OFF” pathway was engaged for halting during feeding, and the “brake” pathway was engaged for halting during grooming. Furthermore, this knowledge of the neural targets and mechanisms for halting, allowed us to use connectomics to predict novel halting pathways that could be relevant in other behavioral contexts.
Unlocking Esophageal Carcinoma’s Secrets: An integrated Omics Approach Unveils DNA Methylation as a pivotal Early Detection Biomarker with Clinical Implications
Authors: Ali Akbar , Zhang Li , Liu Hong-Sheng 
Published: September 2023

1AbstractEsophageal carcinoma (EC) ranks among the top six most prevalent malignancies worldwide with a recent surge in incidence. An innovative integrated omics technique is presented for discerning the two primary types of esophageal carcinoma (EC) AND Squamous cell carcinoma and adenocarcinoma. Utilizing The Cancer Genome Atlas (TCGA) data via Bioconductor, the research integrated DNA methylation and RNA expression analyses for esophageal cancer (ESCA). Key findings revealed DNA methylation’s pivotal role in ESCA progression and its potential as an early detection biomarker. Significant disparities in methylation patterns offered insights into the disease’s pathogenesis. A comparison with the TCGA Pan-Cancer dataset using Bioconductor tools enriched the understanding of ESCA genomics. Specifically, 131,220 hypomethylated probes were detected in tumors compared to 6,248 in healthy tissues. Additionally, 42,060 probe-gene pairs linked methylation variations to expression alterations, with 768 hypomethylated motifs identified. Thirteen of these motifs emerged as potential diagnostic markers. Transcription factor analyses spotlighted crucial regulators, including NFL3, ATF4, JUN, and CEBPG, revealing intricate regulatory networks in ESCA. Survival statistics further correlated clinical factors with patient longevity. This research recommends an innovative approach to identifying oesophageal abnormalities through DNA methylation and gene expression mechanisms. Research suggests DNA methylation may serve as an early detection biomarker, aiding in identifying esophagus cancer prior to more advanced stages.
Democratizing access to microfluidics: Rapid prototyping of open microchannels with low-cost LCD 3D printers
Authors: Leong Kelsey M. , Sun Aileen Y. , Quach Mindy L. , Lin Carrie H. , Craig Cosette A. , Guo Felix , Robinson Timothy R. , Chang Megan , Olanrewaju Ayokunle O. 
Published: September 2023

AbstractMicrofluidics offer user-friendly liquid handling for a range of biochemical applications. 3D printing microfluidics is rapid and cost-effective compared to conventional cleanroom fabrication. Typically, microfluidics are 3D printed using digital light projection (DLP) stereolithography (SLA), but many models in use are expensive (≥$10,000 USD), limiting widespread use. Recent liquid crystal display (LCD) technology advancements have provided inexpensive (<$500) SLA 3D printers with sufficient pixel resolution for microfluidic applications. However, there are only a few demonstrations of microfluidic fabrication, limited validation of print fidelity, and no direct comparisons between LCD and DLP printers. We compared a 40 µm pixel resolution DLP printer (∼$18,000 USD) with a 34.4 µm (<$380) LCD-SLA printer. Consistent with prior work, we observed linear trends between designed and measured channel widths ≥ 4 pixels on both printers, so we calculated accuracy above this size threshold. Using a standard IPA wash resin and optimized parameters for each printer, the average error between designed and measured widths was 2.11 ± 1.26% with the DLP printer and 15.4 ± 2.57% with the 34.4 µm LCD printer. The average coefficient of variation [CV] was ∼2% for both printers. Printing with optimized conditions for a low-cost water wash resin designed for LCD-SLA printers resulted in an average error of 2.53 ± 0.94% with the 34.4 µm LCD printer and 5.35 ± 4.49% with a 22 µm LCD printer. We characterized additional parameters including surface roughness, channel perpendicularity, and light intensity uniformity, and as an application of LCD-printed devices, we demonstrated consistent flow rates in capillaric circuits for self-regulated and self-powered delivery of multiple liquids. In conclusion, LCD printers are an inexpensive alternative for fabricating microfluidics, with minimal differences in fidelity and accuracy compared with a 20X more expensive DLP printer.