bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Interdisciplinary, Comprehensive Recovery Pathway Improves Microsurgical Breast Reconstruction Delivery
Authors: Clark Robert Craig , Segal Rachel , Kordahi Anthony , Sendek Gabriela , Alving-Trinh Alexandra , Abramson Wendy , Sztain Jacklynn , Swisher Matthew , Gabriel Rodney A. , Gosman Amanda , Said Engy T. , Reid Chris M. 
Published: April 2024

Introduction
Free-flap (autologous) breast reconstruction demonstrates superiority over alloplastic approaches but is offered infrequently. Enhanced recovery protocols can address postoperative challenges, but most literature is limited to inpatient interventions and outcomes. This study describes an adoptable, longitudinally comprehensive and multidisciplinary recovery pathway for autologous reconstruction which adds to the current guidelines. The authors aimed to allow perioperative outcomes comparable to alloplastic reconstructions.

Methods
All autologous Comprehensive Recovery Pathway (CRP) subjects from a single surgeon were retrospectively included. A comparator group of equal size was randomly selected from institutional subpectoral and dual-plane tissue expander patients having Enhanced Recovery After Surgery guideline–directed care. All subjects in both cohorts received preoperative paravertebral regional blocks. Operative detail, inpatient recovery, longitudinal morphine equivalents (MEs) required, and complications were compared.

Results
Each cohort included 71 cases (99 breasts). Despite longer operations, intraoperative MEs were fewer in autologous cases (P = 0.02). Morphine equivalents during inpatient stay were similar between cohorts, with both being discharged on median day 2. Multivariate regression demonstrated a 0.8-day increased stay for autologous subjects with additional contribution from bilateral cases, body mass index, and age (P < 0.05). Autologous subjects were regularly discharged postoperative day 1 (17%) and postoperative day 2 (39%), with trend toward earlier discharge (P < 0.01). Outpatient MEs were significantly fewer in autologous subjects, corresponding to a 30- to 150-mg oxycodone difference (P < 0.01). Major complication occurred in 12.7% of autologous and 22.5% of alloplastic subjects (P = 0.11). Flap loss occurred in 1 autologous subject versus 11 alloplastic failures (P < 0.01).

Conclusions
This study details partnership between the plastic surgery service, regional and acute pain anesthesia services, and dedicated nursing with longitudinal optimizations allowing perioperative outcomes improved over current literature. Patients in the CRP used fewer opioids from operation through follow-up with comparable length of stay and significantly fewer reconstructive failures than alloplastic subjects. The pathway may be quickly adopted into academic practice patterns and mitigates traditional barriers, allowing extension of autologous reconstruction offerings.
BZR1 promotes pluripotency acquisition and callus development through direct regulation of ARF7 and ARF19
Authors: Ebstrup E , Ammitsøe T , Blanco-Touriñán N , Hansen J , Hardtke CS , Rodriguez E , Petersen M 
Published: April 2024

AbstractPlants have the remarkable ability to regenerate whole organisms through formation of pluripotent cell masses from somatic cells. Cellular programs leading to fate change of somatic to pluripotent cells resembles lateral root (LR) formation and both are chiefly regulated by auxin. Brassinosteroid signalling also plays an important role during LR formation but little is known about the direct link between auxin and brassinosteroid components, such as BZR1 and BES1, in relation to pluripotency acquisition. Here we show that gain-of-function mutantsbzr1-Dandbes1-Dexhibit altered callus formation, yet disruption of these transcription factors does not produce major changes to callus formation orde novo organogenesis. Moreover, our data reveals that BZR1 displays enhanced expression in callus tissue and directly binds to the promoters of ARF7 and ARF19, two master pluripotency regulators, leading to their enhanced transcription. Remarkably, we see abrogation of callus formation inbzr1-Dupon disruption of ARF7 and ARF19, emphasizing that BZR1 callus phenotype is dependent on these two auxin signalling components. In conclusion, we depict a link between ARF7, ARF19 and BZR1 in the promotion of pluripotency acquisition, portraying BZR1 as a major supporting factor in callus formation.IMPORTANTManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way.Upon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor.The identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report.The identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred.GUIDELINESFor reviewers:https://www.reviewcommons.org/reviewersFor authors:https://www.reviewcommons.org/authorsCONTACTThe Review Commons office can be contacted directly at:office@reviewcommons.org
Genome-wide association study of glucocerebrosidase activity modifiers
Authors: Somerville Emma N. , Krohn Lynne , Senkevich Konstantin , Yu Eric , Ahmad Jamil , Asayesh Farnaz , Ruskey Jennifer A. , Spiegelman Dan , Fahn Stanley , Waters Cheryl , Sardi S. Pablo , Alcalay Roy N. , Gan-Or Ziv 
Published: April 2024

AbstractOne of the most common genetic risk factors for Parkinson’s disease (PD) are variants inGBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GCase deficiency has been associated with an increased PD risk, but not all individuals with low GCase activity are carriers ofGBA1mutations, suggesting other factors may be acting as modifiers. We aimed to discover common variants associated with GCase activity, as well as replicate previously reported associations, by performing a genome-wide association study using two independent cohorts: a Columbia University cohort consisting of 697 PD cases and 347 controls and the Parkinson’s Progression Markers Initiative (PPMI) cohort consisting of 357 PD cases and 163 controls. As expected,GBA1variants have the strongest association with decreased activity, led by p.N370S (beta = -4.36, se = 0.32, p = 5.05e-43). We also identify a novel association in theGAAlocus (encoding for acid alpha-glucosidase, beta = -0.96, se = 0.17, p = 5.23e-09) that may be the result of an interaction between GCase and acid alpha-glucosidase based on various interaction analyses. Lastly, we show that several PD-risk loci are potentially associated with GCase activity. Further research will be needed to replicate and validate our findings and to uncover the functional connection between acid alpha-glucosidase and GCase.
Human BioMolecular Atlas Program (HuBMAP): 3D Human Reference Atlas Construction and Usage
Authors: Börner Katy , Blood Philip D. , Silverstein Jonathan C. , Ruffalo Matthew , Satija Rahul , Teichmann Sarah A. , Pryhuber Gloria , Misra Ravi S. , Purkerson Jeffrey , Fan Jean , Hickey John W. , Molla Gesmira , Xu Chuan , Zhang Yun , Weber Griffin , Jain Yashvardhan , Qaurooni Danial , Kong Yongxin ,   HRA Team, Bueckle Andreas , Herr Bruce W. 
Published: April 2024

AbstractThe Human BioMolecular Atlas Program (HuBMAP) aims to construct a reference 3D structural, cellular, and molecular atlas of the healthy adult human body. The HuBMAP Data Portal (https://portal.hubmapconsortium.org) serves experimental datasets and supports data processing, search, filtering, and visualization. The Human Reference Atlas (HRA) Portal (https://humanatlas.io) provides open access to atlas data, code, procedures, and instructional materials. Experts from more than 20 consortia are collaborating to construct the HRA’s Common Coordinate Framework (CCF), knowledge graphs, and tools that describe the multiscale structure of the human body (from organs and tissues down to cells, genes, and biomarkers) and to use the HRA to understand changes that occur at each of these levels with aging, disease, and other perturbations. The 6th release of the HRA v2.0 covers 36 organs with 4,499 unique anatomical structures, 1,195 cell types, and 2,089 biomarkers (e.g., genes, proteins, lipids) linked to ontologies and 2D/3D reference objects. New experimental data can be mapped into the HRA using (1) three cell type annotation tools (e.g., Azimuth) or (2) validated antibody panels (OMAPs), or (3) by registering tissue data spatially. This paper describes the HRA user stories, terminology, data formats, ontology validation, unified analysis workflows, user interfaces, instructional materials, application programming interface (APIs), flexible hybrid cloud infrastructure, and previews atlas usage applications.
Medical students’ and educators’ opinions of teleconsultation in practice and undergraduate education: a UK-based mixed-methods study
Authors: Wetzlmair Lisa-Christin , O’Malley Andrew , O’Carroll Veronica 
Published: April 2024

AbstractIntroductionAs information and communication technology continues to shape the healthcare landscape, future medical practitioners need to be equipped with skills and competencies that ensure safe, high-quality, and person-centred healthcare in a digitised healthcare system. This study investigated undergraduate medical students’ and medical educators’ opinions of teleconsultation practice in general and their opinions of teleconsultation education.MethodsThis study used a cross-sectional, mixed-methods approach, utilising the additional coverage design to sequence and integrate qualitative and quantitative data. An online questionnaire was sent out to all medical schools in the UK, inviting undergraduate medical students and medical educators to participate. Questionnaire participants were given the opportunity to take part in a qualitative semi-structured interview. Descriptive and correlation analyses and a thematic analysis were conducted.ResultsA total of 248 participants completed the questionnaire and 23 interviews were conducted. Saving time and the reduced risks of transmitting infectious diseases were identified as common advantages of using teleconsultation. However, concerns about confidentiality and accessibility to services were expressed by students and educators. Eight themes were identified from the thematic analysis. The themes relevant to teleconsultation practice were (1) The benefit of teleconsultations, (2) A second-best option, (3) Patient choice, (4) Teleconsultations differ from in-person interactions, and (5) Impact on the healthcare system. The themes relevant to teleconsultation education were (6) Considerations and reflections on required skills, (7) Learning and teaching content, and (8) The future of teleconsultation education.DiscussionThe results of this study have implications for both medical practice and education. Patient confidentiality, safety, respecting patients’ preferences, and accessibility are important considerations for implementing teleconsultations in practice. Education should focus on assessing the appropriateness of teleconsultations, offering accessible and equal care, and developing skills for effective communication and clinical reasoning. High-quality teleconsultation education can influence teleconsultation practice.
Sensitive Pathogen Detection and Drug Resistance Characterization Using Pathogen-Derived Enzyme Activity Amplified by LAMP or CRISPR-Cas
Authors: Wang Qin , Kline Enos C. , Gilligan-Steinberg Shane D. , Lai James J. , Hull Ian T. , Olanrewaju Ayokunle O. , Panpradist Nuttada , Lutz Barry R. 
Published: April 2024

AbstractPathogens encapsulate or encode their own suite of enzymes to facilitate replication in the host. The pathogen-derived enzymes possess specialized activities that are essential for pathogen replication and have naturally been candidates for drug targets. Phenotypic assays detecting the activities of pathogen-derived enzymes and characterizing their inhibition under drugs offer an opportunity for pathogen detection, drug resistance testing for individual patients, and as a research tool for new drug development. Here, we used HIV as an example to develop assays targeting the reverse transcriptase (RT) enzyme encapsulated in HIV for sensitive detection and phenotypic characterization, with the potential for point-of-care (POC) applications. Specifically, we targeted the complementary (cDNA) generation activity of the HIV RT enzyme by adding engineered RNA as substrates for HIV RT enzyme to generate cDNA products, followed by cDNA amplification and detection facilitated by loop-mediated isothermal amplification (LAMP) or CRISPR-Cas systems. To guide the assay design, we first used qPCR to characterize the cDNA generation activity of HIV RT enzyme. In the LAMP-mediated Product-Amplified RT activity assay (LamPART), the cDNA generation and LAMP amplification were combined into one pot with novel assay designs. When coupled with direct immunocapture of HIV RT enzyme for sample preparation and endpoint lateral flow assays for detection, LamPART detected as few as 20 copies of HIV RT enzyme spiked into 25μL plasma (fingerstick volume), equivalent to a single virion. In the Cas-mediated Product-Amplified RT activity assay (CasPART), we tailored the substrate design to achieve a LoD of 2e4 copies (1.67fM) of HIV RT enzyme. Furthermore, with its phenotypic characterization capability, CasPART was used to characterize the inhibition of HIV RT enzyme under antiretroviral drugs and differentiate between wild-type and mutant HIV RT enzyme for potential phenotypic drug resistance testing. Moreover, the CasPART assay can be readily adapted to target the activity of other pathogen-derived enzymes. As a proof-of-concept, we successfully adapted CasPART to detect HIV integrase with a sensitivity of 83nM. We anticipate the developed approach of detecting enzyme activity with product amplification has the potential for a wide range of pathogen detection and phenotypic characterization.
Neural processing of rhythmic speech by children with developmental language disorder (DLD): An EEG study
Authors: Keshavarzi Mahmoud , Richards Susan , Feltham Georgia , Parvez Lyla , Goswami Usha 
Published: April 2024

AbstractSensitivity to rhythmic and prosodic cues in speech has been described as a precursor of language acquisition. Consequently, atypical rhythmic processing during infancy and early childhood has been considered a risk factor for developmental language disorders. Despite many behavioural studies, the neural processing of rhythmic speech has not yet been explored in children with developmental language disorder (DLD). Here we utilise EEG to investigate the neural processing of rhythmic speech by 9-year-old children with and without DLD. In the current study, we investigate phase entrainment, angular velocity, power, event related potentials (ERPs), phase-amplitude coupling (PAC) and phase-phase coupling (PPC), at three frequency bands selected on the basis of the prior literature, delta, theta and low gamma. We predicted a different phase of entrainment in the delta band in children with DLD, and also greater theta power, atypical cross-frequency coupling and possibly atypical gamma-band responses. Contrary to prediction, children with DLD demonstrated significant and equivalent phase entrainment in the delta and theta bands to control children. However, only the control children showed significant phase entrainment in the low gamma band. The children with DLD also exhibited significantly more theta and low gamma power compared to the control children, and there was a significant gamma-band difference in angular velocity between the two groups. Finally, group resultant phase analyses showed that low-frequency phase (delta and theta) affected gamma oscillations differently by group. These EEG data show important differences between children with and without DLD in the neural mechanisms underpinning the processing of rhythmic speech. The findings are discussed in terms of auditory theories of DLD, particularly Temporal Sampling theory.
Gluconeogenesis in the YSL-like tissue of cloudy catshark (Scyliorhinus torazame)
Authors: Shimizu Marino , Takagi Wataru , Sakai Yuki , Kayanuma Isana , Furukawa Fumiya 
Published: April 2024

AbstractGlucose has important roles in the development of hematopoietic stem cells and brain of zebrafish, the vertebrate animal model; however, in most oviparous animals, the amount of maternally provided glucose in the yolk is scarce. For these reasons, developing animals need some ways to supplement glucose. Recently, it was found that developing zebrafish, a teleost fish, undergo gluconeogenesis in the yolk syncytial layer (YSL), an extraembryonic tissue that surrounds the yolk, utilizing yolk nutrients as substrates. However, teleost YSL is evolutionarily unique, and it is not clear how other vertebrates supplement glucose. In this study, we used cloudy catshark, an elasmobranch species which possesses a YSL-like tissue during development, and sought for possible gluconeogenic activities in this tissue. In the catshark yolk sac, an increase in glucose level was found, and our isotope tracking by13C-labeled substrate combined with LC/MS analysis detected gluconeogenic activities with glycerol most preferred substrate. In addition, expression analysis for gluconeogenic genes showed that many of these were expressed at the YSL-like tissue, suggesting that cloudy catshark engages in gluconeogenesis in this tissue. The gluconeogenesis in teleost YSL and a similar tissue in elasmobranch species implies conservation of the mechanisms of yolk metabolism between these two lineages. Future studies on other vertebrate taxa will be helpful to understand the evolutionary changes in the modes of yolk metabolism that vertebrates have experienced.
Targeting the expansion of myeloid-derived suppressor cells in liver cirrhosis
Authors: Flint Emilio , Ercan Caner , Mitchell Eoin , Pop Oltin T , Geng Anne , Jorzik Paul OG , Possamai Lucia , Brenig Robert G , Morel Sarah , Sieber Pablo , Singanayagam Arjuna , Matter Matthias S , Semela David , Heim Markus H , Demougin Philippe , Roux Julien , Terracciano Luigi M , Triantafyllou Evangelos , Bernsmeier Christine 
Published: April 2024

AbstractBackground and aimsPreviously, we identified immune-suppressive circulating monocytic myeloid-derived suppressor cells (M-MDSC) in patients with cirrhosis and liver failure, which increased with disease severity and were associated with infections and mortality. Impaired immune responses and M-MDSC expansion were reversed byex vivopolyinosinic:polycytidylic acid (poly(I:C)) treatment. Here, we aimed to investigate hepatic MDSC subsets in liver biopsies of cirrhotic patients and identify MDSC subsets in murine models to assess the safety and efficacy of poly(I:C)in vivo.Methods22 cirrhotic patients and 4 controls were clinically characterised. MDSC were identified in liver biopsies (immunofluorescence) and in the circulation (flow cytometry). M- MDSC phenotype and function following poly(I:C) stimulation were assessedex vivo. Carbon tetrachloride-based murine models of liver fibrosis were used. Poly(I:C) was administered therapeutically. MDSC biology was investigated with flow cytometry, immunofluorescence and T-cell proliferation assay. Hepatic histopathology, transcriptomics (BulkRNAseq) and serum markers were assessed.ResultsBesides circulating M-MDSC, hepatic CD14+CD84+M-MDSC and CD15+CD84+polymorphonuclear-MDSC expanded in cirrhotic patients and indicated disease severity, infections and poor survival. Poly(I:C) treatment reversed phenotype and function of circulating M-MDSCex vivo. Circulating and hepatic MDSC expanded in our murine models of liver fibrosis and suppressed T-cell proliferation. Lipopolysaccharide andE.colichallenge exacerbated hepatic MDSC and fibrosis compared to CCl4controls. Poly(I:C) therapy reduced MDSC expansion in fibrotic mice with bacterial infection and CCl4-induced fibrosis.ConclusionHepatic MDSC expanded in cirrhotic patients and were linked with disease severity and poor prognosis. Poly(I:C) reversed frequency and function of M-MDSCex vivo. Poly(I:C) therapy reversed MDSC expansion and fibrosis in a murine model of liver fibrosis with infection. Thus, we highlighted poly(I:C) as a potential immunotherapy for the treatment of immuneparesis in cirrhosis.
Reconstructing and comparing signal transduction networks from single cell protein quantification data
Authors: Stohn Tim , van Eijl Roderick , Mulder Klaas W. , Wessels Lodewyk F.A. , Bosdriesz Evert 
Published: April 2024

AbstractMotivationSignal transduction networks regulate a multitude of essential biological processes and are frequently aberrated in diseases such as cancer. Developing a mechanistic understanding of such networks is essential to understand disease or cell population specific signaling and to design effective treatment strategies. Typically, such networks are computationally reconstructed based on systematic perturbation experiments, followed by quantification of signaling protein activity. Recent technological advances now allow for the quantification of the activity of many (signaling) proteins simultaneously in single cells. This makes it feasible to reconstruct signaling networks from single cell data.ResultsHere we introduce single cell Comparative Network Reconstruction (scCNR) to derive signal transduction networks by exploiting the heterogeneity of single cell (phospho)protein measurements. scCNR treats stochastic variation in total protein abundances as natural perturbation experiments, whose effects propagate through the network. scCNR reconstructs cell population specific networks of the same underlying topology for cells from diverse populations. We extensively validated scCNR on simulated single cell data, and we applied it to a dataset of EGFR-inhibitor treated keratinocytes to recover signaling differences downstream of EGFR and in protein interactions associated with proliferation. scCNR will help to unravel the mechanistic signaling differences between cell populations by making use of single-cell data, and will subsequently guide the development of well-informed treatment strategies.Availability and implementationscCNR is available as a python module athttps://github.com/ibivu/scmra. Additionally, code to reproduce all figures is available athttps://github.com/tstohn/scmra_analysis.Supplementary informationSupplementary information and data are available at Bioinformatics online.