bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a novelin-vivovascular injury score for prediction of in-stent restenosis
Authors: Cornelissen Anne , Florescu Roberta Andreea , Reese Stefanie , Behr Marek , Ranno Anna , Manjunatha Kiran , Schaaps Nicole , Böhm Christian , Liehn Elisa Anamaria , Zhao Liguo , Nilcham Pakhwan , Milzi Andrea , Schröder Jörg , Vogt Felix Jan 
Published: March 2023

AbstractBackgroundDespite optimizations of coronary stenting technology, a residual risk of in-stent restenosis (ISR) remains. Vessel wall injury has important impact on the development of ISR. While injury can be assessed in histology, there is no injury score available to be used in clinical practice.MethodsSeven rats underwent abdominal aorta stent implantation. At 4 weeks after implantation, animals were euthanized, and strut indentation, defined as the impression of the strut into the vessel wall, as well as neointimal growth were assessed. Established histological injury scores were assessed to confirm associations between indentation and vessel wall injury. In addition, stent strut indentation was assessed by optical coherence tomography (OCT) in an exemplary clinical case.ResultsStent strut indentation was associated with vessel wall injury in histology. Furthermore, indentation was positively correlated with neointimal thickness, both in the per-strut analysis (r=0.5579) and in the per-section analysis (r=0.8620; both p ≤0.001). In a clinical case, indentation quantification in OCT was feasible, enabling assessment of injuryin vivo.ConclusionAssessing stent strut indentation enables periprocedural assessment of stent-induced damagein vivoand therefore allows for optimization of stent implantation. The assessment of stent strut indentation might become a valuable tool in clinical practice.
Factors affecting the quality of life of acne-suffering adolescents in Honduras, Central America, and its repercussions
Authors: Espinoza-Turcios Eleonora , Chinchilla-Castañeda Kathya , Sosa-Mendoza Carlos , Zambrano Lysien Ivania , Castro Ramos Henry Noel , Armada José , Mejia Cristian R. 
Published: March 2023

AbstractIntroductionAdolescence is a stage of physical, psychological, and social changes, which determine the personality of the individual, which can be influenced by physical appearance because of alterations in the skin texture of adolescents. Patients with dermatosis have a higher risk of developing depression, anxiety and suicidal ideas. Acne is an important factor for quality of life and affects adolescents both physically and psychosocially.ObjectiveTo determine the factors associated with the repercussions of acne in adolescents in Honduras.MethodologyAnalytical cross-sectional study. The Cardiff Acne Disability Index (CADI) scale was used through a questionnaire in Google Forms. Descriptive and analytical statistics were obtained.ResultsOf the 3,272 young participants, with respect to quality of life, 25.8% (845) had medium or high repercussions, 5.3% were very depressed by the appearance of their skin in the month prior to filling out the questionnaire. When multivariate analysis was performed, it was found that those who had medium or high repercussions due to acne were women (RPa: 1.33; 95%CI: 1.20-1.48; p-value<0.001), those of indigenous ethnicity (RPa: 1.36; 95%CI: 1.05-1.75; p-value=0.019), those who had scars on the face (RPa: 13.08; 95%CI: 10.02-17.05; p-value<0.001) or those who had the father (RPa: 1.13; 95%CI: 1.01-1.25; p-value=0.031) or siblings with acne (RPa: 1.16; 95%CI: 1.04-1.28; p-value=0.005).ConclusionIt was found that gender, belonging to an indigenous ethnicity, having scars on the face or that having a close relative who had suffered from acne were associated with medium or high repercussions on the quality of life; it is important to take care of acne in this stage of life to avoid repercussions in adulthood.
Impact of Providing Future Cardiovascular Risk Based on Genetic Testing on Low-Density Lipoprotein Cholesterol in Patients with Familial Hypercholesterolemia (GenTLe-FH): A Randomized Wait-list Controlled Open-Label Trial
Authors: Nomura Akihiro , Okada Hirofumi , Nohara Atsushi , Kawashiri Masaaki , Takamura Masayuki , Tada Hayato 
Published: March 2023

AbstractBackground and AimsFamilial hypercholesterolemia (FH) is an autosomal dominant monogenic disease characterized by high low-density lipoprotein cholesterol (LDL-C) levels. Although carrying causative FH variants is associated with coronary heart disease (CHD), it remains unclear whether disclosing its associated cardiovascular risk affects outcomes in patients with FH. Here, we evaluated the efficacy of providing future cardiovascular risk based on genetic testing in addition to a standard FH education program.MethodsWe conducted a randomized, wait-list controlled, open-label, single-center trial. In the intervention group, we reported a future cardiovascular risk based on the genetic testing adding to standard FH education at week 0. In the wait-list control group, we only disseminated standard FH education according to the guidelines at week 0; they later received a genetic testing-based cardiovascular risk assessment at week 24. The primary endpoint of this study was the plasma LDL-C level at week 24.ResultsFifty eligible patients with clinically diagnosed FH, without a history of CHD, were allocated to the intervention group (n=24) or the wait-list control group (n=26). At week 24, the intervention group had a significantly greater reduction in LDL-C levels than the wait-list control group (mean changes, -13.1 mg/dL vs. 6.6 mg/dL; difference, -19.7 mg/dL; 95% confidence interval, -34 to -5.6; p=0.009). This interventional effect was consistent with FH causative variant carriers but not with non-carriers.ConclusionsIn addition to standard FH care, providing future cardiovascular risk based on genetic testing can further reduce plasma LDL-C levels, particularly among FH causal variant carriers.RegistrationJapan Registry of Clinical Trials (jRCTs04218002). URL:https://jrct.niph.go.jp/latest-detail/jRCTs042180027
Lipoarabinomannan regulates septation inMycobacterium smegmatis
Authors: Sparks Ian L. , Nijjer Japinder , Yan Jing , Morita Yasu S. 
Published: March 2023

AbstractThe growth and division of mycobacteria, which include several clinically relevant pathogens, deviate significantly from that of canonical bacterial models. Despite their Gram-positive ancestry, mycobacteria synthesize and elongate a diderm envelope asymmetrically from the poles, with the old pole elongating more robustly than the new pole. In addition to being structurally distinct, the molecular components of the mycobacterial envelope are also evolutionarily unique, including the phosphatidylinositol-anchored lipoglycans lipomannan (LM) and lipoarabinomannan (LAM). LM and LAM modulate host immunity during infection, but their role outside of intracellular survival remains poorly understood, despite their widespread conservation among non-pathogenic and opportunistically pathogenic mycobacteria. Previously,Mycobacterium smegmatisandMycobacterium tuberculosismutants producing structurally altered LM and LAM were shown to grow slowly under certain conditions and to be more sensitive to antibiotics, suggesting that mycobacterial lipoglycans may support cellular integrity or growth. To test this, we constructed multiple biosynthetic lipoglycan mutants ofM. smegmatisand determined the effect of each mutation on cell wall biosynthesis, envelope integrity, and division. We found that mutants deficient in LAM, but not LM, fail to maintain cell wall integrity in a medium-dependent manner, with envelope deformations specifically associated with septa and new poles. Conversely, a mutant producing abnormally large LAM formed multiseptated cells in way distinct from that observed in a septal hydrolase mutant. These results show that LAM plays critical and distinct roles at subcellular locations associated with division in mycobacteria, including maintenance of local cell envelope integrity and septal placement.SignificanceMycobacteria cause many diseases including tuberculosis (TB). Lipoarabinomannan (LAM) is a lipoglycan of mycobacteria and related bacteria, playing important roles as a surface-exposed pathogen-associated molecular pattern during host-pathogen interactions. Its importance is highlighted by the facts that anti-LAM antibody appears to be protective against TB disease progression, and urine LAM serves as a diagnostic marker for active TB. Given the clinical and immunological relevance of the molecule, it was a striking gap in knowledge that we did not know the cellular function of this lipoglycan in mycobacteria. In this study, we demonstrated that LAM regulates septation, a principle potentially generalizable to other lipoglycans widely found in a group of Gram-positive bacteria that lack lipoteichoic acids.
Probing metazoan polyphosphate biology usingDrosophilareveals novel and conserved polyP functions
Authors: Sarkar Sunayana , Sharma Harsha , Hosen SK Yasir , Ladke Jayashree S , Balasubramanian Deepa , Raran-Kurussi Sreejith , Bhandari Rashna , Jaiswal Manish 
Published: March 2023

AbstractPolyphosphate exists in all life forms; however, its biological functions in metazoans are understudied. Here, we exploredDrosophilaas the first genetic model to explore polyP biology in metazoans. We first established biochemical and in situ methods to detect, quantify, and visualise polyP inDrosophila.We then engineered a FLYX system to deplete polyP in subcellular compartments in a tissue-specific manner. Using these tools, we demonstrated a spatiotemporal and subcellular compartment-specific regulation of polyP levels in various developmental stages and tissue types. We then uncovered that polyP is crucial for hemolymph clotting and developmental timing. These results indicate the evolutionarily conserved role of polyP as theex vivoaddition of polyP accelerates mammalian blood clotting. Further, the transcriptomics analysis of polyP-depleted larvae demonstrates the impact of polyP on several cellular processes including translation. These observations underscore the utility of the toolkit we developed to discover previously unknown polyP functions in metazoans.
Long-term psychological outcomes following stroke: The OX-CHRONIC study
Authors: Kusec Andrea , Milosevich Elise , Williams Owen A. , Chiu Evangeline G. , Watson Pippa , Carrick Chloe , Drozdowska Bogna A. , Dillon Avril , Jennings Trevor , Anderson Bloo , Dawes Helen , Thomas Shirley , Kuppuswamy Annapoorna , Pendlebury Sarah T. , Quinn Terence J. , Demeyere Nele 
Published: March 2023

AbstractBackgroundStroke survivors rate longer-term (>2 years) psychological recovery as their top priority, but data on how frequently psychological consequences occur is lacking. Prevalence of cognitive impairment, depression/anxiety, fatigue, apathy and related psychological outcomes, and whether rates are stable in long-term stroke, is unknown.MethodsN= 105 long-term stroke survivors (M[SD] age = 72.92 [13.01];M[SD] acute NIH Stroke Severity Score = 7.39 [6.25]; 59.0% Male;M[SD] years post-stroke = 4.57 [2.12]) were recruited (potentialN= 208). Participants completed 3 remote assessments, including a comprehensive neuropsychological battery, and questionnaires on emotional distress, fatigue, apathy and other psychological outcomes. Ninety participants were re-assessed one year later. Stability of outcomes was assessed by Cohen’sdeffect size estimates and percent Minimal Clinically Important Difference changes between time points.ResultsOn the Montreal Cognitive Assessment 65.3% scored <26. On the Oxford Cognitive Screen 45.9% had at least one cognitive impairment. Attention (27.1%) and executive function (40%) were most frequently impaired. 23.5% and 22.5% had elevated depression/anxiety respectively. Fatigue (51.4%) and apathy (40.5%) rates were high. Attention (d= −0.12; 85.8% stable) and depression (d= 0.09, 77.1% stable) were the most stable outcomes. Following alpha-adjustments, only perceptuomotor abilities (d= 0.69; 40.4% decline) and fatigue (d= −0.33; 37.2% decline) worsened over one year. Cognitive impairment, depression/anxiety, fatigue and apathy all correlated with worse quality of life.ConclusionNearly half of participants >2 years post-event exhibited psychological difficulties, which impact long-term quality of life. Stroke is a chronic condition requiring long-term psychological support.
Lower vaccination coverage against COVID-19 in school-aged children is associated with low socioeconomic status in the Metropolitan Area of Santiago, Chile
Authors: Guerrero-Araya Enzo , Ravello Cesar , Rosemblatt Mario , Perez-Acle Tomas 
Published: March 2023

AbstractBackgroundThe burden of COVID-19 has been heterogeneous, indicating that the effects of this disease are synergistic with both other non-communicable diseases and socioeconomic status (SES), high-lighting its syndemic character. While the appearance of vaccines has moderated the pandemic effects, their coverage has also been heterogeneous, both when comparing different countries, and when comparing different populations within countries. Of note, once again SES appears to be a correlated factor.MethodsTo examine the relationship between SES and vaccination coverage, we analyzed publicly available data detailing the percentage of school-aged vaccinated children in different municipalities belonging to the Metropolitan Area (MA) of Santiago, Chile, one of the most largely vaccinated countries in the world. Vaccination data was compiled per school type, either public, state-subsidized and private, at three different dates along the COVID-19 pandemic so to cover the dispersion ofDelta, andOmicron, includingOmicronsubvariants BA.4 and BA.5. We computed the median vaccination ratio for each municipality and school type and calculated their Spearman’s rank correlation coefficient with each one of nine SES indices.FindingsIn the MA of Santiago, Chile, the percentage of school-age children who have received vaccinations against COVID-19 correlates with SES. Vulnerable municipalities with low SES exhibit low levels of vaccination coverage. Of note, this strong correlation is observed in both public and state-subsidized schools, but to a meaningless extent in private schools. Although inequity in vaccination coverage decreases over time, it remains higher among students enrolled either in public and state-subsidized schools compared to those of private schools.InterpretationAvailable data is insufficient to explore plausible causes behind lower vaccination coverage in vulnerable municipalities in the MA of Santiago, Chile. However, considering the available literature, it is likely that a combination of factors including the lack of proper information about the importance of vaccination, the lack of incentives for children’s vaccination, low trust in the government, and/or limited access to vaccines for lower-income people, may all have contributed to this low vaccination coverage. Importantly, unless corrected, the inequity in vaccination coverage will exacerbate the syndemic nature of COVID-19.FundingThis material is based upon work supported by the U.S. Air Force Office of Scientific Research under award number FA9550-20-1-0196. Financial support is also acknowledged to Centro Ciencia & Vida, FB210008, Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID.
Distinct role of TGN-resident clathrin adaptors for Rab5 activation in the TGN-endosome trafficking pathway
Authors: Nagano Makoto , Aoshima Kaito , Shimamura Hiroki , Siekhaus Daria Elisabeth , Toshima Junko Y. , Toshima Jiro 
Published: March 2023

AbstractClathrin-mediated vesicle trafficking plays central roles in the post-Golgi transport pathways from thetrans-Golgi network (TGN) to endosomes. In yeast, two clathrin adaptors – AP-1 complex and GGA proteins (GGAs) – are predicted to generate distinct transport vesicles at the TGN, and epsin-related Ent3p/Ent5p act as accessories for these adaptors. Recently, we showed that vesicle transport from the TGN, rather than from the plasma membrane, is crucial for Rab5-mediated endosome formation, and that Ent3p/5p are crucial for this process, whereas AP-1 and GGAs are dispensable. However, these observations were incompatible with previous studies showing that these adaptors are required for Ent3p/5p recruitment to the TGN, and thus the overall mechanism responsible for regulation of Rab5 activity remains ambiguous. Here we investigated the functional relationships between clathrin adaptors in post-Golgi-mediated Rab5 activation. We were able to show that AP-1 disruption inent3Δ/5Δ mutant impairs Rab5-GEF Vps9p transport to the Rab5 compartment, and severely reduces Rab5 activity. Additionally, GGAs, Golgi-resident PI4 kinase Pik1p and Rab11 GTPases Ypt31p/32p were found to have partially overlapping functions for recruitment of AP-1 and Ent3p/5p to the TGN. These findings suggest a distinct role of clathrin adaptors for Rab5 activation in the TGN-endosome trafficking pathway.
Temporal perturbation of STAT1/2 activity reveals dynamic ligand discrimination of type I interferon signaling
Authors: Yang Haowen , van de Kreeke Thomas , Van Eyndhoven Laura C. , Tel Jurjen 
Published: March 2023

SUMMARYType-I interferon (IFN-I) subtypes signal through the same IFNα receptor (IFNAR), and initiate temporal STAT1/2 activation to orchestrate innate and adaptive immunity. It remains unknown how IFNAR discriminates between subtypes (e.g., IFNα and IFNβ), and how STAT1/2 signaling is affected by time-varying inputs. Here, we utilize our microfluidic system and live-cell imaging to quantify STAT1/2 activation dynamics in a reporter fibroblast model. Population-averaged and single-cell analyses reveal distinct STAT1/2 responses to various IFNα and IFNβ inputs. Upon continuous stimulation, cells show less sensitivity but more sustained responses to IFNα over IFNβ. A short IFNα pulse induces nearly homogeneous STAT1/2 dynamics, in contrast to heterogeneous responses in IFNβ-pulsed cells. Distinct STAT1/2 refractory states emerge upon exposure to repeated IFN-I pulses, while alternating pulse stimulation reveals that IFNβ can revoke STAT1/2 refractoriness caused by IFNα, but not vice versa. These findings highlight the differences between IFNα and IFNβ signaling and how they can elicit distinct temporal cellular behaviors during viral infection.
β-actin is essential for structural integrity and physiological function of the retina
Authors: Vedula Pavan , Fina Marie E. , Bell Brent A. , Nikonov Sergei S. , Kashina Anna , Dong Dawei W. 
Published: March 2023

SummaryLack of non-muscleβ-actin gene (Actb) leads to early embryonic lethality in mice, however mice withβ- toγ-actin replacement develop normally and show no detectable phenotypes at young age. Here we investigated the effect of this replacement in the retina. During aging, these mice have accelerated de-generation of retinal structure and function, including elongated microvilli and defective mitochondria of retinal pigment epithelium (RPE), abnormally bulging photoreceptor outer segments (OS) accompanied by reduced transducin concentration and light sensitivity, and accumulation of autofluorescent microglia cells in the subretinal space between RPE and OS. These defects are accompanied by changes in the F-actin binding of several key actin interacting partners, including ezrin, myosin, talin, and vinculin known to play central roles in modulating actin cytoskeleton and cell adhesion and mediating the phagocytosis of OS. Our data show thatβ-actin protein is essential for maintaining normal retinal structure and function.
Quantitative proteomics and phosphoproteomics of PPP2R5D variants reveal deregulation of RPS6 phosphorylation through converging signaling cascades
Authors: Smolen KA , Papke CM , Swingle MR , Musiyenko A , Li C , Camp AD , Honkanen RE , Kettenbach AN 
Published: March 2023

AbstractVariants in the phosphoprotein phosphatase-2 regulatory protein-5D gene (PPP2R5D) cause the clinical phenotype of Jordan’s Syndrome (PPP2R5D-related disorder), which includes intellectual disability, hypotonia, seizures, macrocephaly, autism spectrum disorder and delayed motor skill development. The disorder originates fromde novosingle nucleotide mutations, generating missense variants that act in a dominant manner. Pathogenic mutations altering 13 different amino acids have been identified, with the E198K variant accounting for ∼40% of reported cases. Here, we use CRISPR-PRIME genomic editing to introduce a transition (c.592G>A) in thePPP2R5Dallele in a heterozygous manner in HEK293 cells, generating E198K-heterozygous lines to complement existing E420K variant lines. We generate global protein and phosphorylation profiles of wild-type, E198K, and E420K cell lines and find unique and shared changes between variants and wild-type cells in kinase- and phosphatase-controlled signaling cascades. As shared signaling alterations, we observed ribosomal protein S6 (RPS6) hyperphosphorylation, indicative of increased ribosomal protein S6-kinase activity. Rapamycin treatment suppressed RPS6 phosphorylation in both, suggesting activation of mTORC1. Intriguingly, our data suggest AKT-dependent (E420K) and -independent (E198K) activation of mTORC1. Thus, although upstream activation of mTORC1 differs between PPP2R5D-related disorder genotypes, treatment with rapamycin or a p70S6K inhibitor warrants further investigation as potential therapeutic strategies for patients.
Perceptions of equity in leader peer learning groups
Authors: Loeffler Kurstyn , Wittmer Jenell Lynn-Senter 
Published: March 2023

Purpose
Peer groups have been established as one of the best tools for leadership learning for family business leaders. However, these groups remain underutilized because business leaders disengage and voluntarily create turnover from these groups. This study explores the perceptions of family business leaders concerning the usefulness, growth opportunities, and equity within peer learning groups to determine what factors impact retention in these groups.

Design/methodology/approach
Two surveys were administered to 321 family business owners and leaders through three large family business centers in different regions of the United States. Leaders were grouped into those who left versus those who remained in a peer learning group. Data were collected about their learning experiences and why they remained or voluntarily left a group.

Findings
Lack of equity was found to be the main determinant of turnover in peer learning groups. Peer learning groups need to consist of business owners along the same trajectory, career stage, and in similar stages of growing a family business in order to equally contribute to the group’s learning. Business leaders who are in peer learning groups they report as being equal also report that their groups are more helpful, trustworthy and create better-quality learning experiences.

Originality/value
Peer groups are important for peer-to-peer learning and continued education for family business leaders. Having a group of peers whom have dealt with similar issues can help business leaders overcome problems successfully. However, little research exists that examines what factors make these peer groups successful.