bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing a Perioperative Mind-Body Intervention for Peripheral Vascular Interventions
Authors: Maximilian C. Y. , Mehta Darshan , Dua Anahita , Stephen Antonia , Bruce Alex M. , Forsythe Aynsley , Chitilian Hovig V. , Bringle Erik J. , Simpson James C. , Parady Katherine M. , McNeil Lisa A. , Baim Margaret A. , Eagleton Matthew J. , Chang David C. , Yeh Gloria Y. 
Published: June 2024

BackgroundPeripheral vascular interventions (PVIs) performed under procedural sedation and analgesia (PSA) can be associated with anxiety and poor compliance with patient instructions during surgery. Mind-body interventions (MBIs) such as meditation have demonstrated the potential to decrease perioperative anxiety, though this area is understudied, and no tailored interventions have been developed for the vascular surgical patient population.ObjectivesWe aimed to design a perioperative MBI that specifically targeted vascular surgical patients undergoing PVIs under PSA. We sought to perform this in a scientifically rigorous, multi-disciplinary collaborative manner.MethodsFollowing the Obesity-Related Behavioral Intervention Trials (ORBIT) model, we designed (Phase 1a) and then refined (Phase 1b) a MBI for patients undergoing PVIs under PSA to decrease perioperative anxiety and sedation and facilitate patient intraoperative compliance. Phase 1a involved a literature review, informal information gathering and synthesis, and drafting a preliminary protocol for a perioperative MBI. Phase 1b involved assembling a multi-disciplinary expert panel of perioperative and mind-body clinicians and researchers to improve the MBI using an iterative, modified Delphi approach.ResultsThe modified Delphi process was completed, and a consensus was reached after three iterations. The resulting MBI consisted of two seven-minute preoperative guided meditations on the day of surgery, including diaphragmatic breathing, body scans, and guided imagery emphasizing awareness of the ipsilateral leg where the vascular surgery was performed. A document delineating the integration of the MBI into the operating room workflow was produced, including details regarding the intervention’s timing, duration, and modality.ConclusionUsing a multi-specialty expert panel, we designed a novel MBI in the form of a guided meditation with elements of mindfulness and guided imagery to decrease anxiety and increase intraoperative compliance for patients undergoing PVIs under PSA. A prospective pilot study is being planned to test the program’s feasibility.
The Effect of Metformin Treatment on the Circulating Proteome
Authors: Connolly Ben , McCreight Laura , Slieker Roderick C , Bedair Khaled F , Donnelly Louise , de Klerk Juliette A , Beulens JWJ , Elders PM ,   IMI-DIRECT,   IMI-RHAPSODY, Bergström Göran , Hong Mun-Guan , Koivula Robert W. , Franks Paul W. , ‘t Hart Leen , Schwenk Jochen M , Gummesson Anders , Pearson Ewan R 
Published: June 2024

ObjectiveMetformin is one of the most used drugs worldwide. However, its mechanism of action remains uncertain. Given the potential to reveal novel insights into the pleiotropic effects of metformin treatment, we aimed to undertake a comprehensive analysis of circulating proteins.Research Design and MethodsWe analysed 1195 proteins using the SomaLogic platform in 1175 participants, using cross- sectional data from the GoDARTS and DCS cohorts; 450 proteins using the Olink platform in 784 participants, using cross-sectional data from IMI-DIRECT; and combined longitudinal data from the IMPOCT, RAMP and S3WP-T2D cohorts with 372 proteins in 98 participants using the Olink platform. Finally, we performed systems level analysis on the longitudinal OLINK data to identify any possible relationships for the proteins changing concentration following metformin exposure.ResultsOverall, 97 proteins were associated with metformin exposure in at least one of the studies (Padj<0.05), and 10 proteins (EpCAM, SPINK1, t-PA, Gal-4, TFF3, TF, FAM3C, COL1A1, SELL, CD93) were associated in two independent studies. Four proteins, REG4, GDF15, REG1A, and OMD were consistently associated across all studies and platforms. Gene-set enrichment analysis revealed that the effect of metformin exposure was on intestinal tissues. In the longitudinal analysis 18% of proteins were significantly altered by metformin.ConclusionsThese data provide further insight into the mechanism of action of metformin, potentially identifying novel targets for diabetes treatment, and highlight the need to account for metformin exposure in proteomic studies and where protein biomarkers are used for clinical care where metformin treatment will generate false positive results.HighlightsIn the most comprehensive proteomic analysis of metformin exposure to date, we showed 97 proteins to be associated with metformin exposure in at least one study.14 proteins were consistently associated with metformin exposure in 2 or more platforms or studies.Gene enrichment analysis shows that the strongest protein set is of intestinal origin.These data provide further insight into the mechanism of action of metformin, potentially identify novel targets for diabetes treatment and highlight the need to account for metformin exposure in proteomic studies and where protein biomarkers are used for clinical care.
Piloting a minimum data set for older people living in care homes in England: a developmental study
Authors: Gordon Adam L , Rand Stacey , Crellin Elizabeth , Allan Stephen , Tracey Freya , De Corte Kaat , Lloyd Therese , Brine Richard , Carroll Rachael E , Towers Ann-Marie , Burton Jennifer Kirsty , Akdur Gizdem , Hanratty Barbara , Webster Lucy , Palmer Sinead , Jones Liz , Meyer Julienne , Spilsbury Karen , Killett Anne , Wolters Arne T , Peryer Guy , Goodman Claire 
Published: June 2024

AbstractBackgroundWe developed a prototype minimum data set (MDS) for English care homes, assessing feasibility of extracting data directly from digital care records (DCRs) with linkage to health and social care data.MethodsThrough stakeholder development workshops, literature reviews, surveys and public consultation we developed an aspirational MDS. We identified ways to extract this from existing sources including DCRs and routine health and social care datasets. To address gaps we added validated measures of delirium, cognitive impairment, functional independence and Quality of Life to DCR software. Following routine health and social care data linkage to DCRs, we compared variables recorded across multiple data sources, using a hierarchical approach to reduce missingness where appropriate. We reported proportions of missingness, mean and standard deviation (SD) or frequencies (%) for all variables.ResultsWe recruited 996 residents from 45 care homes in three English Integrated Care Systems. 727 residents had data included in the MDS. Additional data were well completed (<35% missingness at wave 1). Competition for staff time, staff attrition, and software-related implementation issues contributed to missing DCR data. Following data linkage and combining variables where appropriate, missingness was reduced (<=4% where applicable).DiscussionIntegration of health and social care is predicated on access to data and interoperability. Despite governance challenges we safely linked care home DCRs to statutory health and social care datasets to create a viable prototype MDS for English care homes. We identified issues around data quality, governance, data plurality and data completion essential to MDS implementation going forward.Key pointsThere is a range of resident information across DCRs, health and social care datasets, which can be combined to provide a more complete picture of residents.We developed and implemented a Minimum Dataset linking care home digital care records to statutory health and social care records.Information governance for linking data across multiple data owners and data processors is complex and time consuming.Standardisation across Digital Care Records Systems would enable data to be used more effectively across the care home sector.Establishing shared priorities across key stakeholders interested in care home data is essential for effective MDS implementation.
Association of Post-Acute Sequelae of COVID-19 with respiratory system diagnoses: a population-based case-control study of Region Stockholm
Authors: Lindberg Pia , Ljunggren Gunnar , Lee Seika , Kolosenko Iryna , Runold Michael , Piontkovskaya Kristina , Wachtler Caroline , Fedorowski Artur , Carlsson Axel C. , Wheelock Åsa M. 
Published: June 2024

ABSTRACTObjectivesPost Acute Sequelae of COVID-19 (PASC) is an important health concern after the COVID-19 pandemic. We aimed to investigate the prevalence of respiratory system disorders before and after the pandemic onset in individuals with and without PASC.MethodsWe designed a case-control study was designed to investigate the prevalence of respiratory system-related diagnoses in adult, non-hospitalized PASC patients (cases) in 2019, 12 months before and 6 months after the PASC diagnosis compared to matched controls without PASC. Data was extracted from the Stockholm Region’s database warehouse (VAL).ResultsHigher diagnostic rates for common respiratory illnesses were observed among PASC patients in 2019 and 12 months before PASC diagnosis, which then slightly decreased 6 months after PASC diagnosis. PASC patients showed more pre-pandemic respiratory diagnoses compared to controls: in 2019 they had higher incidence of acute upper respiratory tract infection (OR 2.47 for males, 2.22 for females), asthma (OR 1.76 (males), 1.95 (females)), and bronchitis (OR 2.15 (males), 2.71 (females)) compared to controls.ConclusionsThis study highlights that individuals with PASC have a higher prevalence of respiratory disorders both before and after their COVID-19 diagnosis. Notably, asthma and other respiratory conditions were more common in PASC patients compared to matched controls. Our study demonstrates that individuals with asthma are more likely to develop PASC, even if asthma does not increase the severity of acute COVID-19. These findings underscore the need for further investigation into the underlying mechanisms connecting respiratory illnesses and PASC. Understanding the long-term consequences of COVID-19 in individuals with pre-existing conditions will be crucial for refining clinical management strategies and improving patients outcomes.
Student learning performance and satisfaction with a flipped classroom in undergraduate dental pharmacology education
Authors: Galvin Shelia , Lucitt Margaret 
Published: June 2024

AbstractIntroductionThe flipped classroom (FC) model of blended learning has become more feasible with the advancement of digital technology platforms. Monitoring a FC approach in curriculum delivery provides an opportunity to evaluate its impact on student exam outcomes and satisfaction. Presented here is examination performances and learning experiences in undergraduate dental students taking pharmacological course material using a FC approach compared to that of a traditional classroom (TC) model.MethodNinety- seven students experiencing a FC delivery is compared to 129 students taking a TC approach over 2 academic years. Course lecture topics, scheduling and assessment are consistent across both modes of delivery. At the end of each academic year an anonymous student survey with a closed end question was conducted to gain student feedback regarding course satisfaction.ResultsThe FC positively improved student examination performances compared to the TC approach with a seven percent increase in the percentage mean exam grade and a 15% increase in the number of students obtaining exam grades greater than 50%. An increase in the proportion of students achieving higher grades overall is seen in the FC versus the TC approach from the frequency distribution of exam results. The students also rated the FC more positively in the feedback satisfaction compared to the TC student cohort.ConclusionIn summary the student exam grades and feedback here indicate the FC having a positive impact on student outcomes and experience compared to the TC approach. These findings provide evidence to dental pharmacological educators that a FC curriculum delivery can lead to an improvement in student performances in this subject area.
Tumor Spectrum and Temporal Cancer Trends in adult carriers of Li-Fraumeni syndrome: Implications for Personalized Screening Strategies inTP53R337H carriers
Authors: Galante Pedro A. F. , Guardia Gabriela D. A. , Pisani Janina , Sandoval Renata L. , Barros-Filho Mateus C. , Gifoni Ana Carolina Leite Vieira Costa , Patrão Diogo F. C. , Ashton-Prolla Patricia , de Vasconcellos Vitor Fiorin , Freycon Claire , Levine Arnold , Hainaut Pierre , Achatz Maria Isabel 
Published: June 2024

SUMMARYBackgroundLi-Fraumeni Syndrome (LFS) is a predisposition associated with early onset malignant tumors caused by germline pathogenic variants in the TP53 gene. Although rare worldwide, LFS is prevalent in Southern Brazil due to a founder pathogenic variant, c.1010G>A, p.Arg337His (R337H), discovered through its association with risk of childhood adrenal cortical carcinoma.MethodsHere, we have analyzed tumor patterns, cancer risk, sex differences and temporal tumor trends in a cohort of 303 adult R337H carriers and we have compared them with those of 405 adult carriers of otherTP53variants typical of LFS.FindingsCompared to the latter, R337H carriers had a lower cumulative risk of developing cancer (54% for R337H vs 78% for otherTP53variants at age 50 years). Female R337H carriers were at a higher risk than males (65% vs 30% at age 50 years) and had a higher risk of developing a second primary cancer, underscoring a strong sex bias not observed in carriers of other variants. The most common cancers were breast (75%), soft tissue sarcoma (9%) and lung cancer (8%) in females, and soft tissue sarcoma (30%), prostate (13%) and lung cancer (12%) in males. Common second malignancies were breast cancer in females and lung cancer in males.InterpretationsOverall, this study confirms that R337H is associated with a lifetime risk of multiple cancers of the LFS spectrum but with incomplete penetrance, particularly in males. Our findings suggest that R337H carriers would benefit from adapted lifetime and surveillance strategies for risk reduction.FundingSão Paulo Research Foundation and Hospital Sírio-Libanês.
Absence of Evidence is Not Evidence of Absence:The many flaws in the case against transgenerational epigenetic inheritance of pathogen avoidance inC. elegans
Authors: Kaletsky Rachel , Moore Rebecca , Sengupta Titas , Seto Renee , Ceballos-Llera Borja , Murphy Coleen T. 
Published: June 2024

AbstractAfter examining the data and methods presented in Gainey, et al.,bioRxiv, 20241we conclude that the authors did not use an experimental paradigm that would have allowed them to replicate our results on transgenerational epigenetic inheritance (TEI) of learned avoidance that we regularly observe2–5. That is, we agree with the authors that their experiments show no evidence of TEI. However, there are substantial differences in their execution of every step of the work that also make it impossible for the authors to claim that they are replicating our experiments or protocols. Based on these differences, we do not believe there is an issue of “robustness” and “reliability” in our TEI findings, but rather that Hunter and colleagues have in fact not tested thecentralcondition of TEI - that is, small RNA production by bacteria and subsequent uptake byC. elegans- nor have they carried out proper behavioral and imaging assays to assess this behavior. Our subsequent work shows that indeed this example of transgenerational epigenetic inheritance is not just observed in laboratory settings with PA14, but is also induced by wild strains ofPseudomonas, exhibiting its robustness. Just as we offered advice and training to Hunter and colleagues, we are happy to advise anyone who wishes to learn this assay.We have now performed the experiments in the absence of azide, a deviation from our protocol that Hunter and colleagues deliberately made, and found that this omission may account for most if not all of the differences from our results. It is disingenuous for the authors to have presented their work as if they have used our protocol, given the fact that they chose to not use the same conditions for the most basic assay used in the work, the chemotaxis assay, which would have been necessary to replicate in order to reproduce our work. Therefore, Gainey et al.’s claims that our protocol or results are “irreproducible” are not supported by their evidence.
Peptidomimetic inhibitors targeting TrkB/PSD-95 signaling improves cognition and seizure outcomes in an Angelman Syndrome mouse model
Authors: Huie Emily Z. , Yang Xin , Rioult-Pedotti Mengia S. , Naik Mandar , Huang Yu-Wen Alvin , Silverman Jill L , Marshall John 
Published: June 2024

AbstractAngelman syndrome (AS) is a rare genetic neurodevelopmental disorder with profoundly debilitating symptoms with no FDA-approved cure or therapeutic. Brain-derived neurotrophic factor (BDNF), and its receptor TrkB, have a well-established role as regulators of synaptic plasticity, dendritic outgrowth, dendritic spine formation and maintenance. Previously, we reported that the association of PSD-95 with TrkB is critical for intact BDNF signaling in the AS mouse model, as illustrated by attenuated PLCγ and PI3K signaling and intact MAPK pathway signaling. These data suggest that drugs tailored to enhance the TrkB-PSD-95 interaction may provide a novel approach for the treatment of AS and a variety of NDDs. To evaluate this critical interaction, we synthesized a class of high-affinity PSD-95 ligands that bind specifically to the PDZ3 domain of PSD-95, denoted as Syn3 peptidomimetic ligands. We evaluated Syn3 and its analog D-Syn3 (engineered using dextrorotary (D)-amino acids)in vivousing theUbe3aexon 2 deletion mouse model of AS. Following systemic administration of Syn3 and D-Syn3, we demonstrated improvement in the seizure domain of AS. Learning and memory using the novel object recognition assay also illustrated improved cognition following Syn3 and D-Syn3, along with restored long-term potentiation. Finally, D-Syn3 treated mice showed a partial rescue in motor learning. Neither Syn3 nor D-Syn3 improved gross exploratory locomotion deficits, nor gait impairments that have been well documented in the AS rodent models. These findings highlight the need for further investigation of this compound class as a potential therapeutic for AS and other genetic NDDs.
CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly
Authors: Mathiowetz Alyssa J. , Meymand Emily S. , Deol Kirandeep K. , Parlakgül Güneş , Lange Mike , Pang Stephany P. , Roberts Melissa A. , Torres Emily F. , Jorgens Danielle M. , Zalpuri Reena , Kang Misun , Boone Casadora , Zhang Yaohuan , Morgens David W. , Tso Emily , Zhou Yingjiang , Talukdar Saswata , Levine Tim P. , Ku Gregory , Arruda Ana Paula , Olzmann James A. 
Published: June 2024

AbstractImbalances in lipid storage and secretion lead to the accumulation of hepatocyte lipid droplets (LDs) (i.e., hepatic steatosis). Our understanding of the mechanisms that govern the channeling of hepatocyte neutral lipids towards cytosolic LDs or secreted lipoproteins remains incomplete. Here, we performed a series of CRISPR-Cas9 screens under different metabolic states to uncover mechanisms of hepatic neutral lipid flux. Clustering of chemical-genetic interactions identified CLIC-like chloride channel 1 (CLCC1) as a critical regulator of neutral lipid storage and secretion. Loss of CLCC1 resulted in the buildup of large LDs in hepatoma cells and knockout in mice caused liver steatosis. Remarkably, the LDs are in the lumen of the ER and exhibit properties of lipoproteins, indicating a profound shift in neutral lipid flux. Finally, remote homology searches identified a domain in CLCC1 that is homologous to yeast Brl1p and Brr6p, factors that promote the fusion of the inner and outer nuclear envelopes during nuclear pore complex assembly. Loss of CLCC1 lead to extensive nuclear membrane herniations, consistent with impaired nuclear pore complex assembly. Thus, we identify CLCC1 as the human Brl1p/Brr6p homolog and propose that CLCC1-mediated membrane remodeling promotes hepatic neutral lipid flux and nuclear pore complex assembly.
The Leader of the Capsid protein fromFeline calicivirusmust be palmitoylated and form oligomers through disulfide bonds for efficient viral replication
Authors: Peñaflor-Téllez Yoatzin , Gómez de la Madrid Jaury , Monge-Celestino Erick Ignacio , Pérez-Ibáñez Carolina , Miguel-Rodríguez Carlos Emilio , Gutiérrez-Escolano Ana Lorena 
Published: June 2024

ABSTRACTFeline calicivirus(FCV), a member of theVesivirusgenus and a model for studying of the members of theCaliciviridae, has been used to understand the biology and viral replication of etiological agents of medical and veterinary importance. The leader of the capsid (LC) protein is exclusive to theVesivirusgenus members whose importance for a successful viral replication has been demonstrated; however, its cell localization, post-translational modifications, and specific functions throughout the viral replication cycle are poorly understood. We have determined that the expression of the LC protein from FCV in a virus-free system is located at the mitochondria and induces apoptosis; furthermore, thein vitrocharacterization of a purified LC protein showed that it has viroporin characteristics. Here, using an LC-reactive serum, the LC protein expression kinetics, cellular localization, post-translational modifications, and association with cellular PDI proteins in FCV infected cells was determined. We found that the LC protein is present on the membrane of infected cells and in the supernatants, independently of cell lysis, which suggests that it is actively secreted. Moreover, we found that LC protein is palmitoylated during infection and that palmitoylation inhibition alters its levels and subcellular localization. Finally, we determined that the LC protein forms oligomers dependent on disulfide bonds mediated by PDI activity. In addition, it interacts with PDIA3, a disulfide isomerase known as an important factor in the replication of several viruses. The results indicate that the LC protein from FCV might have multiple roles during FCV replication.IMPORTANCEFeline calicivirus (FCV) is a highly transmissible virus that represents a significant cause of upper respiratory infection in domestic and wild cats worldwide. FCV also serves as one of the most valuable models for studying calicivirus biology, as unlike most members of the family, known to cause diseases in animals and humans, it can be easily grown in cell culture. Since there are no efficacious vaccines or antivirals against most caliciviruses, studying their molecular biology and the relationship between viral and cellular components is essential for developing strategies for their prevention and control.