bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Efficacy of 3D Virtual Surgery, CAD/CAM, and 3D Printing Technology for Maxillomandibular Advancement in Obstructive Sleep Apnea Patients
Authors: Ha Sung-Ho , Oh Ji-Seok , Jeong Chun-Gi , Baek Seung-Hak , Choi Jin-Young 
Published: March 2023

Objective:Maxillomandibular advancement (MMA) is the most effective surgical method for treating obstructive sleep apnea, and it moves the maxillomandibular complex forward to increase the entire upper airway volume. By using 3-dimensional (D) virtual surgery, computer-aided design/computer-aided manufacturing, and 3D printing technologies, it is possible to overcome all the limitations of conventional methods.Materials and Methods:In this study, (modified) MMA was performed by applying 3D technologies to obstructive sleep apnea patients. Virtual surgery was done as surgical plan, cutting guides, and customized plates were made by computer-aided design/computer-aided manufacturing and 3D printing technologies for surgical procedures.Results:After surgery, all patients improved their appearance, quality of sleep, and sleep apnea level were dramatically improved. Through these results, it was found that there are many advantages in using 3D technologies for preparing and implementing MMA.Conclusions:It was confirmed that the accuracy and efficiency of surgery were increased by applying 3D technologies. This suggests that 3D technologies are very useful tools in surgical area.
Risk Factors for Acute Postoperative Complications Following Operative Management of Le Fort Fractures—A NSQIP Study
Authors: Wood Matabele Kasey Leigh , Seitz Allison J. , Doan Ton C. , Poore Samuel O. 
Published: March 2023

Introduction:
Le Fort fractures comprise a pattern of complex midfacial fractures that arise secondarily to craniofacial trauma. Although management of these fractures has been detailed within the literature, there is a paucity of research examining postoperative outcomes after surgical repair. The primary aim of this study is to assess patient outcomes after operative management of Le Fort fractures, and examine factors influencing the risk for developing postoperative complications, through utilization of the ACS-NSQIP database.

Methods:
The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for cases recorded between 2012 and 2019 with International Classification of Disease (ICD)-9 and ICD-10 codes corresponding to Le Fort fractures. Patient demographics, clinical variables, and postoperative variables were recorded. Logistic regression analysis was conducted to identify independent risk factors for postoperative complications.

Results:
Identification of cases with appropriate ICD codes, and exclusion of those with missing data, yielded 562 patients for analysis. There were no cases of minor complications and 14 cases of severe complications (3 cases of wound dehiscence, 3 cases of transfusion requirement, 1 case of failure to wean from the ventilator for more than 48 h, 1 pulmonary embolism, and 8 cases of reoperation), corresponding to an overall complication rate of 2.49%. Logistic regression analysis revealed steroid use as an independent predictor of severe postoperative complications (OR =13.73, 95% CI: 1.08–128.02, P=0.02).

Conclusion:
The present study is the first to conduct a risk factor analysis of patients with Le Fort fractures using the ACS-NSQIP national database. The overall postoperative complication rate was 2.49%, with 14 cases of complications recorded in 8 years. Although this may suggest that surgical management of Le Fort fractures is generally well-tolerated, it should be noted that this problem is frequently associated with other severe injuries of the head and neck that may influence patient prognosis. Given this, further analysis would benefit from a larger patient cohort and longer postoperative data as the ACS-NSQIP database only records outcomes within 30 days.
A single-nucleus transcriptome-wide association study implicates novel genes in depression pathogenesis
Authors: Zeng Lu , Fujita Masashi , Gao Zongmei , White Charles C. , Green Gilad S. , Habib Naomi , Menon Vilas , Bennett David A. , Boyle Patricia A. , Klein Hans-Ulrich , De Jager Philip L. 
Published: March 2023

AbstractBackgroundDepression is a common psychiatric illness and global public health problem. However, our limited understanding of the biological basis of depression has hindered the development of novel treatments and interventions.MethodsTo identify new candidate genes for therapeutic development, we examined single-nucleus RNA sequencing (snucRNAseq) data from the dorsolateral prefrontal cortex (N=424) in relation to ante-mortem depressive symptoms. To complement these direct analyses, we also used genome- wide association study (GWAS) results for depression (N=500,199) along with genetic tools for inferring the expression of 22,159 genes in 7 cell types and 55 cell subtypes to perform transcriptome-wide association studies (TWAS) of depression followed by Mendelian randomization (MR).ResultsOur single-nucleus TWAS analysis identified 71 causal genes in depression that have a role in specific neocortical cell subtypes; 59 of 71 genes were novel compared to previous studies. Depression TWAS genes showed a cell type specific pattern, with the greatest enrichment being in both excitatory and inhibitory neurons as well as astrocytes. Gene expression in different neuron subtypes have different directions of effect on depression risk. Compared to lower genetically correlated traits (e.g. body mass index) with depression, higher correlated traits (e.g., neuroticism) have more common TWAS genes with depression. In parallel, we performed differential gene expression analysis in relation to depression in 55 cortical cell subtypes, and we found that genes such asANKRD36,MADD,TAOK3,SCAIandCHUKare associated with depression in specific cell subtypes.ConclusionsThese two sets of analyses illustrate the utility of large snucRNAseq data to uncover both genes whose expression is altered in specific cell subtypes in the context of depression and to enhance the interpretation of well-powered GWAS so that we can prioritize specific susceptibility genes for further analysis and therapeutic development.
FERROKINETIC EVALUATION OF PATIENTS WITH ACUTE CORONARY SYNDROME AT A SOUTH AMERICAN HOSPITAL, PILOT STUDY
Authors: Dulcey Sarmiento Luis Andres , Theran Leon Juan Sebastián , Peña Valentina Cabrera , Parales Strauch Rafael Guillermo , Caltagirone Raimondo , Blanco Pimiento Edgar Camilo , Ciliberti Artavia María Paula , Martinez Juan Camilo 
Published: March 2023

AbstractIntroductionAlterations in the ferrokinetic profile are associated with cardiovascular disease, and the short- and long-term prognosis of these alterations is currently unknown.DesignProspective cohort analytical observational studyMethodsTo determine the prognostic value of the alterations of the ferrokinetic profile in patients with myocardial infarction with and without ST-segment elevation, in a Health institution from July 2017 to May 2018. Results : From72patients, the main affected gender was male, in ages over 56 years old, the infarction with ST elevation being the most frequent. Among the associated comorbidities, the main one was hypertension with (n: 22; 53.7%) for infarction with elevation and (n: 23; 74.2%) for infarction without ST elevation. The most frequent alteration of the parameters of the ferrokinetic profile studied, was the iron deficit, found in (n:15; 36.6%) of the patients with ST elevation and (n:13; 41.9%) without ST elevation. Low levels of hemoglobin were present at admission (n:10; 24.4%) of the subgroup with ST elevation and (n:10; 32.3%) for no ST elevation, increasing the percentage to (n:13; 31.7%) (RR: 2) (95% CI -0.131-30.63), associated with low hemoglobin values at day 7 of hospitalization. There were 2 deaths (2.77%), which presented low levels of iron without anemia and infarction with ST elevation complicated by cardiogenic shock.Conclusionsiron deficiency is a common comorbidity with a high mortality rate, and the decrease in hemoglobin after hospital admission was related to mortality, so both parameters should be taken into account in Infarction and cardiovascular disease.
Exploiting public databases of genomic variation to quantify evolutionary constraint on the branch point sequence in 30 plant and animal species
Authors: Nosková Adéla , Li Chao , Wang Xiaolong , Leonard Alexander S. , Pausch Hubert , Kadri Naveen Kumar 
Published: March 2023

AbstractThe branch point sequence is a degenerate intronic heptamer required for the assembly of the spliceosome during pre-mRNA splicing. Disruption of this motif may promote alternative splicing and eventually cause phenotype variation. Despite its functional relevance, the branch point sequence is not included in most genome annotations. Here, we predict branch point sequences in 30 plant and animal species and attempt to quantify their evolutionary constraints using public variant databases. We find an implausible variant distribution in the databases from 16 of 30 examined species. Comparative analysis of variants from whole-genome sequencing shows that biased or erroneous variants that are widespread in public databases cause these irregularities. We then investigate evolutionary constraint with largely unbiased public variant databases in 14 species and find that the fourth and sixth position of the branch point sequence are more constrained than coding nucleotides. Our findings show that public variant databases should be scrutinized for possible biases before they qualify to analyze evolutionary constraint.
Identification ofToxoplasmaCalcium Dependent Protein Kinase 3 as a Stress-Activated Elongation Factor 2 Kinase
Authors: Lis Agnieszka , Baptista Carlos Gustavo , Dahlgren Kelsey , Corvi Maria M. , Blader Ira J. 
Published: March 2023

ABSTRACTToxoplasma gondiiis an obligate intracellular parasite whose tachyzoite form causes disease via a lytic growth cycle. Its metabolic and cellular pathways are primarily designed to ensure parasite survival within a host cell. But during its lytic cycle tachyzoites are exposed to the extracellular milieu and prolonged exposure requires activation of stress response pathways that include reprogramming the parasite proteome. Regulation of protein synthesis is therefore important for extracellular survival. We previously reported that in extracellularly stressed parasites that the elongation phase of protein synthesis is negatively regulated by theToxoplasmaoxygen sensing protein, PhyB. PhyB acts by promoting the activity of elongation factor eEF2, which is a GTPase that catalyzes the transfer of the peptidyl-tRNA from the A site to the P site of the ribosome. In the absence of PhyB, eEF2 is hyper-phosphorylated, which inhibits eEF2 from interacting with the ribosome. eEF2 kinases are atypical calcium-dependent kinases and BLAST analyses revealed the parasite kinase, CDPK3, as the most highly homologous to theSaccharomyces cerevisiaeeEF2 kinase,RCK2. In parasites exposed to extracellular stress, loss of CDPK3 leads to decreased eEF2 phosphorylation and enhanced rates of elongation. Furthermore, co-immunoprecipitation studies revealed that CDPK3 and eEF2 interact in stressed parasites. Since CDPK3 and eEF2 normally localize to the plasma membrane and cytosol, respectively, we investigated how the two can interact. We report that under stress conditions that CDPK3 is not N-myristoylated likely leading to its cytoplasmic localization. In summary, we have identified a novel function for CDPK3 as the first protozoan extracellular-stress induced eEF2 kinase.IMPORTANCEHere, we identify the first protozoan kinase that phosphorylate elongation factor 2 and demonstrate that it is part of an integrated stress response.
HRD-One: CLINICAL VALIDATION AND PERFORMANCE ASSESSMENT. Comparison between Myriad’s myChoice®, SOPHiA GENETICS® SOPHiA Homologous Recombination Solution and AmoyDx® HRD Focus Panel
Authors: Guarischi-Sousa Rodrigo , Kroll José Eduardo , Bonaldi Adriano , Pierry Paulo Marques , de Almeida Luiz Gustavo , Souza Camila Alves , Silva Juliana Santos , Villela Darine , Meliso Fabiana Marcelino , Milanezi Maria Fernanda Grillo , Neto Cristovam Scapulatempo , Yamamoto Guilherme Lopes 
Published: March 2023

ABSTRACTHomologous Recombination Repair (HRR) testing has become increasingly important in clinical genomic labs due to the use of poly-ADP-ribose polymerase (PARP) inhibitor therapy for epithelial ovarian, fallopian tube, or peritoneum cancer. While sequencing and copy number variation analysis can identify patients with a pathogenic mutation in BRCA1 or BRCA2 who can benefit from PARPi therapy, there are also patients who may benefit but do not have these mutations. To address this, our lab has developed a test called HRD-One, in partnership with SOPHiA GENETICS, that can detect sequence variants in genes involved in HRR, as well as genomic scars that indicate Homologous Recombination Deficiency (HRD), which may be present even when a pathogenic variant is not detected. We tested 59 high-grade serous epithelial ovarian cancer samples using HRD-One and found that it had an overall categorical concordance of 94.74% with Myriad’s myChoice® score, which is a commercial HRD test. 12 out of 13 samples that carried a pathogenic or likely pathogenic variant in BRCA1/2 also had a positive HRD-One score, and 9 samples in which a pathogenic variant in BRCA1/2 was not identified had a positive score in both HRD-One and myChoice®. Of the samples that passed quality control, we observed an average of 1.62 points variation between replicates on a scale from -25.0 to +25.0. We also found that low-confidence results were associated with a low DNA input and the age of FFPE blocks, while the estimated tumor percentage in the block, NGS library yield, and score of genomic instability did not have a significant association. We determined that blocks older than 3 years or with a DNA input of less than 25ng are not reliable for producing high-quality results. Finally, we validated the HRD-One test with SOPHiA Homologous Recombination Solution (Library Prep kit II) and correlated it to myChoice®, and found that the AmoyDx® HRD Focus Panel had the same sensitivity but a higher number of false positive samples and therefore lower specificity. Overall, we have shown that HRD-One can provide a reproducible and concordant score for inferring HRD, and an HRD-One score of 2.0 or greater predicts HRD and correlates to Myriad’s myChoice® score of 42 in high-grade serous epithelial ovarian cancers samples that meet our minimum quality criteria.
Prognostic whole-genome and transcriptome signatures in colorectal cancers
Authors: Nunes Luís , Li Fuqiang , Wu Meizhen , Luo Tian , Hammarström Klara , Lundin Emma , Ljuslinder Ingrid , Mezheyeuski Artur , Edqvist Per-Henrik , Löfgren-Burström Anna , Zingmark Carl , Edin Sofia , Larsson Chatarina , Mathot Lucy , Osterman Erik , Osterlund Emerik , Ljungström Viktor , Neves Inês , Yacoub Nicole , Guðnadóttir Unnur , Birgisson Helgi , Enblad Malin , Ponten Fredrik , Palmqvist Richard , Uhlén Mathias , Wu Kui , Glimelius Bengt , Lin Cong , Sjöblom Tobias 
Published: March 2023

ABSTRACTColorectal cancer (CRC) is caused by a sequence of somatic genomic alterations affecting driver genes in core cancer pathways1. To understand the functional and prognostic impact of cancer-causing somatic mutations, we analysed the whole genomes and transcriptomes of 1,063 primary CRCs in a population-based cohort with long-term follow-up. From the 96 mutated driver genes, 9 were novel to CRC and 24 to any cancer. Two distinct patterns of pathway co-mutations were observed, timing analyses identified 6 early and 3 late driver gene mutations, and several new signatures of CRC specific mutational processes were uncovered. Mutations in 10 protein-coding genes belonging to the WNT, EGFR, and TGF-β pathways, 2 mitochondrial DNA genes and 3 regulatory elements along with the COSMIC SBS44 signature impacted survival. Gene expression classification yielded 5 prognostic subtypes with distinct molecular features, in part explained by underlying genomic alterations. Microsatellite instable tumours could be divided in two classes with different levels of hypoxia and infiltration of immune and stromal cells. This study constitutes the largest integrated genome and transcriptome analysis of CRC to date, and links mutations, gene expressions and patient outcomes. The identification of prognostic mutations and expression subtypes can guide future efforts to individualize CRC therapy.
Prognostic Value of Patient-Reported Outcomes in Predicting Long-term Mortality after Transcatheter Aortic Valve Replacement (TAVR)
Authors: Alarouri Hasan S. , Ponce Alejandra Chavez , Mahayni Abdulah , Samimi Sahar , Alkhouli Mohamad 
Published: March 2023

AbstractBackgroundPatient-reported outcome measures (PROM) have been shown to have important prognostic value after various cardiac interventions. We assessed the association between the change in Kansas City Cardiomyopathy Questionnaire 12 (KCCQ-12) score after transcatheter aortic valve replacement (TAVR) and mortality.MethodsWe included patients who underwent TAVR at Mayo Clinic between February 2012, and June 2022, who completed KCCQ-12 prior to and 30-45 days after the procedure. Patients were categorized into 3 groups: those who experienced significant (≥ 19 points;group-1), modest (1-19 points;group-2), and no improvement (≤ 0 points;group-3).ResultsA total of 1,124 patients were included: 60.8% males; 97.6% Caucasian. Mean age was 79.4±8.3 years, KCCQ-12 score was 53.9±24.5, and median STS score was 4.9% (interquartile range 3.1-8.0). At 45 days, the mean change in KCCQ-12 score was 19±24 points: 46.3% (n= 520) of patients had a significant improvement in their KCCQ-12 score, while 33.4% (n= 375) and 20.4% (n = 229) had modest and no improvement, respectively. Median survival was higher in group-1 (5.7±0.2 years) compared to groups 2 and 3 (5.1±0.3 and 4.1±0.4 years, respectively;P<.001). Compared to patients in group 1, those in groups 2 and 3 had higher long-term risk-adjusted mortality (adjusted hazard ratio 1.64; 95%CI 1.28-2.10, and 2.44; 95%CI, 1.84-3.24, respectively).ConclusionPatients who experience modest or no improvement in KCCQ-12 score after TAVR have substantially higher long-term mortality. Delta KCCQ-12 is a cost-effective, efficient tool that can identify patients at increased risk of death at long-term follow-up post-TAVR.Clinical PerspectiveWhat is New?This study documents the prognostic value of the Kansas City Cardiomyopathy Questionnaire 12 score in predicting long-term survival after TAVR.Modest or no improvement in the Kansas City Cardiomyopathy Questionnaire 12 score after TAVR is associated with a considerably higher long-term mortality risk.What are the Clinical Implications?Changes in the Kansas City Cardiomyopathy Questionnaire 12 score may identify patients with higher residual mortality risk after transcatheter aortic valve replacement.
Chromosome-level assemblies of thePieris manniibutterfly genome suggest Z-origin and rapid evolution of the W chromosome
Authors: Blattner Lucas A. , Ruffener Simona , Berner Daniel 
Published: March 2023

AbstractThe insect order Lepidoptera (butterflies and moth) represents the largest group of organisms with ZW/ZZ sex determination. While the origin of the Z chromosome predates the evolution of the Lepidoptera, the W chromosome is considered younger, but its origin is debated. To shed light on the origin of the lepidopteran W, we here produce chromosome-level genome assemblies for the butterflyPieris mannii, and compare the sex chromosomes within and betweenP. manniiand its sister speciesP. rapae. Our analyses clearly indicate a common origin of the W chromosomes of the twoPierisspecies, and reveal similarity between the Z and W in chromosome sequence and structure. This supports the view that the W originates from Z-autosome fusion rather than from a redundant B chromosome. We further demonstrate the extremely rapid evolution of the W relative to the other chromosomes and argue that this may preclude reliable conclusions about the origin of the W based on comparisons among distantly related Lepidoptera. Finally, we find that sequence similarity between the Z and W chromosomes is greatest toward the chromosome ends, perhaps reflecting selection for the maintenance of recognition sites essential to chromosome segregation. Our study highlights the utility of long-read sequencing technology for illuminating chromosome evolution.SignificanceLepidoptera (butterflies and moths) typically exhibit a ZW/ZZ sex determination system, but the origin of the W chromosome is controversial. Based on a chromosome-level reference genome for the Southern Small white butterfly and comparative genomic analyses, we propose that the W chromosome in this group of butterflies derives from the Z chromosome and evolves extremely rapidly.
Entrepreneurial education and entrepreneurial intention among higher education students in Vietnam: do entrepreneurial self-efficacy and family support matter?
Authors: Pham Hong Hai , Le Thi Loan 
Published: March 2023

PurposeThe current study aims to explain the relationship between entrepreneurial education and entrepreneurial intention through a moderated mediation model from the lens of social cognitive career theory (SCCT). Specifically, two main objectives of this study are (1) to explore the mediation role of entrepreneurial self-efficacy in the relationship between entrepreneurial education and start-up intention and (2) to investigate the moderate role of family support on the effect of entrepreneurial education on entrepreneurial intention.Design/methodology/approachThis study uses a sample of 1879 students in Vietnam and SPSS PROCESS macro developed by Hayes (2012) to examine the indirect effect of entrepreneurial education on start-up intention via entrepreneurial self-efficacy and the moderated mediation effect of family support.FindingsThis study reveals that the association between entrepreneurial education and entrepreneurial intention is partially mediated via entrepreneurial self-efficacy. Also, the effect of entrepreneurial education on entrepreneurial self-efficacy and start-up intention was negatively moderated by family support. Furthermore, the indirect effect of entrepreneurial education on intention to form a venture via entrepreneurial self-efficacy is also negatively moderated by family support.Originality/valueThe entrepreneurial education and start-up intention linkage remain a significant gap in the entrepreneurship literature. Therefore, this research study is expected to contribute to clarifying this linkage by utilizing the SCCT to explain how entrepreneurial education contributes to entrepreneurial intention.
Impacts of adopting a new management practice: Operational Coaching™
Authors: Tinelli Michela , Ashley-Timms Dominic , Ashley-Timms Laura , Phillips Ruth 
Published: March 2023

PurposeThis article reports the results of a randomized field experiment that tested the effects of a new business intervention among managers of small- and medium-sized enterprises (SMEs) in England.Design/methodology/approachIndividual managers (learners) were randomly assigned in clusters (companies) to either an intervention group (265 learners; 40 SMEs) receiving a novel virtual, blended training program designed to stimulate a change in management behavior or a no-intervention group (118 learners; 22 SMEs).FindingsThe results show that the primary objective of changing management behavior to use more of an Operational Coaching™ style of management has been achieved (to a statistically significant level), and this is against the backdrop of the devastating COVID-19 pandemic. Positive trends in SME productivity metrics were also observed in the intervention group companies.Originality/valueThese important results could be indicative of the economic and productivity impact that a change in management behavior could have, and they warrant serious further investigation.