bluuebunny/crossref_metadata_2025_split huggingface dataset:
Olfactory Ensheathing Cells Mediate Neuroplastic Mechanisms After Olfactory Training in Mouse Model
Authors: Kim Boo-Young , Park JuYeon , Kim EuiJin , Kim ByungGuk 
Published: February 2020

Background Several studies have reported beneficial effects of olfactory training (OT) on the olfactory nervous system. However, the mechanisms underlying the regeneration of the olfactory system induced by OT are still under investigation. Objectives To determine the key mechanisms involved in the olfactory system recovery and to assess the neuroplastic effects of OT. Methods Thirty healthy female C57BL/6 mice were randomly allocated to 4 groups: control, n = 6; anosmia (no treatment), n = 8; OT, n = 8; and steroid treatment; n = 8. Except for the control group, mice were administered 3-methylindole. Anosmia was assessed using a food-finding test (FFT). The olfactory neuroepithelium was for histological examinations, gene ontology with pathway analyses, RNA, and protein studies. Results FFT was significantly reduced at 3 weeks in the OT mice versus steroids (78.27 s vs 156.83 s, P < .008) and controls (78.27 s vs 13.14 s, P < .003), although final outcome in the FFT was similar in these groups. Expression of olfactory and neurogenesis marker was higher in the olfactory neuroepithelium of the OT group than in the anosmia group without treatment. The mechanisms underlying olfactory regeneration might be related to early olfactory receptor stimulation, followed by neurotrophic factor stimulation of neuronal plasticity. Conclusion OT can improve olfactory function and accelerate olfactory recovery. The mechanisms underlying olfactory regeneration might be related to an initial stimulation of olfactory receptors followed by neurogenesis. Olfactory ensheathing cells might play an important role in olfactory regeneration following OT, based on the observed changes in messenger ribonucleic acid (mRNA) and protein expression, as well as the findings of the gene analysis.
High prevalence of physical inactivity after heart valve surgery and its association with long-term mortality: A nationwide cohort study
Authors: Kim Sun-Hyung , Cha Seungwoo , Kang Seongmin , Han Kyungdo , Paik Nam-Jong , Kim Won-Seok 
Published: February 2020

Abstract

Aims
Physical activity (PA) and systematic efforts, such as cardiac rehabilitation, are recommended by several national guidelines for those who have received heart valve surgery. However, only a few studies have demonstrated real-world situations, such as changes in the PA level after heart valve surgery, and their effects on long-term outcomes. We designed this study to investigate the changes in PA after heart valve surgery and their associations with mortality using nationwide representative data.

Methods
This study was performed using the Korean National Health Insurance Service database. We included patients who received heart valve surgery from 2009 to 2015 and underwent regular health checkups before and after surgery. Subjects were grouped according to their PA level before and after the surgery. Information on all-cause mortality was obtained until 31 December 2016, with a maximum follow-up period of 5 years.

Results
Of the 6587 subjects, 3258 (49.5%) were physically inactive after surgery. Among patients who were physically active (n = 3070), 1196 (39.0%) became inactive after surgery. The postoperative ‘inactive’ group showed higher mortality than the ‘active’ group (hazard ratio (HR): 1.41, 95% confidence interval (CI): 1.08–1.83). The ‘inactive/inactive’ group showed the highest risk of mortality (HR: 1.69, 95% CI: 1.19–2.40) compared with the ‘active/active’ group.

Conclusions
Insufficient PA level after heart valve surgery is associated with higher risk of mortality. However, maintaining sufficient PA after heart valve surgery may be challenging for many patients. Therefore, systematic efforts, such as cardiac rehabilitation, should be considered in those who received heart valve surgery.
Elucidating the Mechanism of Action of CC-90009, a Novel Cereblon E3 Ligase Modulator, in AML Via Genome-Wide CRISPR Screen
Authors: Lu Gang , Surka Christine , Lu Chin-Chun , Jang In Sock , Wang Kai , Rolfe Mark 
Published: February 2020

CC-90009 is a novel cereblon E3 ligase modulator (CELMoD) currently under investigation in a phase I clinical study in relapsed or refractory acute myeloid leukemia (R/R AML) (CC-90009-AML-001; NCT02848001). CC-90009 coopts the CUL4-DDB1-CRBN-RBX1 (CRL4CRBN) E3 ubiquitin ligase complex to target the translation termination factor G1 to S phase transition 1 (GSPT1) for ubiquitination and proteasomal degradation, resulting in rapid induction of apoptosis and growth inhibition in AML cell lines and primary patient blasts.
To further elucidate the mechanism of action of CC-90009 in AML, we performed a genome-wide CRISPR/Cas9 screen to identify gene(s) whose knockout abrogate(s) the response to CC-90009 in a sensitive AML cell line. In addition to well-established key regulatory proteins required for the activity of all known cereblon modulators, which include components of the CRL4CRBN complex, E2 ubiquitin conjugating enzymes UBE2G1 and UBE2D3, and members of the neddylation and deneddylation machinery, interestingly, the screen identified the ILF2 and ILF3 heterodimeric complex as a novel regulator of cereblon expression. Knockout of ILF2/ILF3 decreased the production of full-length CRBN transcript via modulating alternative splicing of CRBN mRNA, leading to significant downregulation of cereblon expression and hence diminished response to CC-90009. The screen also revealed that mTOR signaling and the integrated stress response (ISR) specifically regulate the response to CC-90009 in contrast to other cereblon modulators. Since CC-90009 inhibits protein translation, it is reasonable to expect interactions with regulators of this pathway. Hyperactivation of the mTOR pathway by inactivation of TSC1 and TSC2 protected against the growth inhibitory effect of CC-90009 , at least in part by reducing CC-90009 induced binding of GSPT1 to cereblon and subsequent GSPT1 degradation. On the other hand, GSPT1 degradation promoted the activation of the GCN1/GCN2/ATF4 pathway and subsequent apoptosis in AML cells. Loss of GCN2 significantly attenuated the growth inhibitory effect of CC-90009, and this effect can be rescued with GCN2 wild-type but not enzymatically-dead mutants.
Collectively, the antitumor activity of CC-90009, a first-in-class GSPT1 degrader, in AML cell lines is mediated by multiple layers of signaling networks and machinery, the elucidation of which reveals the underlying mechanism by which CC-90009 exerts its anti-AML activity and informs on the pathways for further study of CC-90009's clinical utility.

Disclosures
Lu: Celgene Corporation: Employment, Equity Ownership. Surka:Celgene: Employment, Equity Ownership. Lu:Celgene Corporation: Employment, Equity Ownership. Jang:Celgene: Employment, Equity Ownership. Wang:Celgene: Employment, Equity Ownership. Rolfe:Celgene: Employment, Equity Ownership.
A phase 1 study of azacitidine with high-dose cytarabine and mitoxantrone in high-risk acute myeloid leukemia
Authors: Cahill Kirk E. , Karimi Yasmin H. , Karrison Theodore G. , Jain Nitin , Green Margaret , Weiner Howard , Fulton Noreen , Kadri Sabah , Godley Lucy A. , Artz Andrew S. , Liu Hongtao , Thirman Michael J. , Le Beau Michelle M. , McNerney Megan E. , Segal Jeremy , Larson Richard A. , Stock Wendy , Odenike Olatoyosi 
Published: February 2020

Abstract
In this phase 1 study, azacitidine (AZA) was given before high-dose cytarabine (HiDAC) and mitoxantrone (mito) based on the hypothesis that epigenetic priming with a hypomethylating agent before cytotoxic chemotherapy would improve response rates in patients with high-risk acute myeloid leukemia (AML), including relapsed/refractory disease. The primary objective was to establish the recommended phase 2 dose of AZA given before standard HiDAC/mito. In a dose escalation scheme, 46 patients (median age, 66 years) received AZA at 37.5, 50, or 75 mg/m2 subcutaneously or IV once daily on days 1 to 5 followed by HiDAC (3000 mg/m2) and mitoxantrone (30 mg/m2) once each on days 6 and 10 (the HiDAC/mito dose was reduced 33% in elderly subjects). Two dose-limiting toxicities occurred (both in the same patient): acute liver failure and kidney injury at the 50 mg/m2 dose. The 30-day induction death rate was 2.2% (1 of 46). The overall response rate, including complete remission and complete remission with incomplete count recovery, was 61% (28 of 46). Previously untreated patients aged ≥60 years with therapy-related AML and de novo AML were more likely to respond than untreated patients with AML progressing from an antecedent hematologic disorder (myelodysplastic syndrome and chronic myelomonocytic leukemia). Patients with favorable European Leukemia Network risk (P = .008), NPM1 mutations (P = .007), or IDH2 mutations (P = .03) were more likely to respond, and those with TP53 mutations (P = .03) were less likely to respond. The recommended phase 2 dose of AZA is 75 mg/m2 per day on days 1 to 5 followed by HiDAC (3000 mg/m2) and mitoxantrone (30 mg/m2) once each on days 6 and 10. This trial was registered at www.clinicaltrials.gov as #NCT01839240.
Materials selection for structured horizontal road markings: financial and environmental case studies
Authors: Burghardt Tomasz E. , Pashkevich Anton 
Published: February 2020

Abstract
Introduction
On majority of roads, horizontal road markings are essential safety feature that must be periodically renewed to maintain appropriate performance.

Results
The use of a premium road marking system resulted in prolonged the service life as compared to a standard system, which would be financially-neutral in the long term despite much higher unit and initial costs; advantageously, 54% less glass beads and 63% less paint would be required over 10-year life cycle. When these products usage savings are recalculated into raw materials consumption, the premium system would demand about 21% more of titanium dioxide, but that would be offset by approximately 25% reduction in the consumption of acrylic resin and circa 97% reduction in organic solvents usage and emissions.

Conclusions
The results from this analysis can be used by road administrators to select the best systems, by policy makers seeking minimisation of environmental impacts, and by contractors who won performance tenders.
Improved recovery of cell-cycle gene expression in Saccharomyces cerevisiae from regulatory interactions in multiple omics data
Authors: Panchy Nicholas L. , Lloyd John P. , Shiu Shin-Han 
Published: February 2020

AbstractBackgroundGene expression is regulated by DNA-binding transcription factors (TFs). Together with their target genes, these factors and their interactions collectively form a gene regulatory network (GRN), which is responsible for producing patterns of transcription, including cyclical processes such as genome replication and cell division. However, identifying how this network regulates the timing of these patterns, including important interactions and regulatory motifs, remains a challenging task.ResultsWe employed four in vivo and in vitro regulatory data sets to investigate the regulatory basis of expression timing and phase-specific patterns cell-cycle expression inSaccharomyces cerevisiae. Specifically, we considered interactions based on direct binding between TF and target gene, indirect effects of TF deletion on gene expression, and computational inference. We found that the source of regulatory information significantly impacts the accuracy and completeness of recovering known cell-cycle expressed genes. The best approach involved combining TF-target and TF-TF interactions features from multiple datasets in a single model. In addition, TFs important to multiple phases of cell-cycle expression also have the greatest impact on individual phases. Important TFs regulating a cell-cycle phase also tend to form modules in the GRN, including two sub-modules composed entirely of unannotated cell-cycle regulators (STE12-TEC1andRAP1-HAP1-MSN4).ConclusionOur findings illustrate the importance of integrating both multiple omics data and regulatory motifs in order to understand the significance regulatory interactions involved in timing gene expression. This integrated approached allowed us to recover both known cell-cycles interactions and the overall pattern of phase-specific expression across the cell-cycle better than any single data set. Likewise, by looking at regulatory motifs in the form of TF-TF interactions, we identified sets of TFs whose co-regulation of target genes was important for cell-cycle expression, even when regulation by individual TFs was not. Overall, this demonstrates the power of integrating multiple data sets and models of interaction in order to understand the regulatory basis of established biological processes and their associated gene regulatory networks.
Presence–absence polymorphisms of single-copy genes in the stony coral Acropora digitifera
Authors: Takahashi-Kariyazono Shiho , Sakai Kazuhiko , Terai Yohey 
Published: February 2020

Abstract
Background
Despite the importance of characterizing genetic variation among coral individuals for understanding phenotypic variation, the correlation between coral genomic diversity and phenotypic expression is still poorly understood.

Results
In this study, we detected a high frequency of genes showing presence–absence polymorphisms (PAPs) for single-copy genes in Acropora digitifera. Among 10,455 single-copy genes, 516 (5%) exhibited PAPs, including 32 transposable element (TE)-related genes. Five hundred sixteen genes exhibited a homozygous absence in one (102) or more than one (414) individuals (n = 33), indicating that most of the absent alleles were not rare variants. Among genes showing PAPs (PAP genes), roughly half were expressed in adults and/or larvae, and the PAP status was associated with differential expression among individuals. Although 85% of PAP genes were uncharacterized or had ambiguous annotations, 70% of these genes were specifically distributed in cnidarian lineages in eumetazoa, suggesting that these genes have functional roles related to traits related to cnidarians or the family Acroporidae or the genus Acropora. Indeed, four of these genes encoded toxins that are usually components of venom in cnidarian-specific cnidocytes. At least 17% of A. digitifera PAP genes were also PAPs in A. tenuis, the basal lineage in the genus Acropora, indicating that PAPs were shared among species in Acropora.

Conclusions
Expression differences caused by a high frequency of PAP genes may be a novel genomic feature in the genus Acropora; these findings will contribute to improve our understanding of correlation between genetic and phenotypic variation in corals.
Indirect impact of violent events on emergency department utilization and disease patterns
Authors: Makhlouf-Obermeyer Carla , Sharara Eman , El-Eid Ghada , Hitti Eveline A. 
Published: February 2020

Abstract
Background
The health effects of war and armed conflict on casualties and mental health of those directly exposed has been well described, but few studies have explored the indirect health effects of violent events. This paper assesses the indirect health impact of several violent events that took place in Beirut in 2013–2014 on ED visit utilization and disease patterns.

Methods
As tracked by media reports, there were 9 violent events in Beirut during 2013–2014. We compared visits to the Emergency Department of a major medical center during weeks when violent events happened and weeks without such events (the preceding week and the same week in preceding years). After re-coding de-identified data from the medical records of 23,067 patients, we assessed differences in the volume of visits, severity index, and discharge diagnoses. Individual control charts were used to analyze ED visit trends post-event.

Results
Comparisons of weeks with violent events and weeks without such events indicate that the socio-demographic characteristics of patients who visited the Emergency Department were similar. Patients seen during violent weeks were significantly more likely to be admitted to the hospital, and less likely to present with low acuity complaints, indicating greater complexity of their conditions. The discharge diagnoses that were significantly higher during violent event weeks included anxiety disorders, sprains, and gastritis. Daily ED visits dropped post events by 14.111%, p < 0.0001.

Conclusions
The results indicate that violent events such as bombs, explosions, and terrorist attacks reverberate through the population, impact patterns of ED utilization immediately post-event and are associated with adverse health outcomes, even among those who are not directly affected by the events.
Appendectomy, cholecystectomy and diagnostic laparoscopy conducted before pregnancy and risk of adverse birth outcomes: a nationwide registry-based prevalence study 1996–2015
Authors: Rasmussen Anne Staub , Christiansen Christian Fynbo , Uldbjerg Niels , Nørgaard Mette 
Published: February 2020

Abstract
Background
Non-obstetric surgery conducted during pregnancy may increase the risk of adverse birth outcomes like small for gestational age, preterm birth, and miscarriage. Mechanisms are unclear but possibly longer lasting. We examined whether appendectomy, cholecystectomy and diagnostic laparoscopy conducted before pregnancy affect these outcomes.

Methods
This nationwide Danish prevalence study included all pregnancies during 1996–2015 that had an appendectomy, cholecystectomy or diagnostic laparoscopy registered before last menstrual period in the years 1992–2015. We excluded pregnancies with surgery and categorized pre-pregnancy surgery according to timing (0–11, 12–23, and 24+ months before last menstrual period). Outcomes were small for gestational age, late preterm birth (32–37 weeks), early preterm birth (22–31 weeks) and miscarriage (7–21 weeks). We computed absolute risks and used logistic regression comparing pregnancies with surgery 0–11 or 12–23 to 24+ months before last menstrual period, computing odds ratios for each outcome, adjusting for maternal age and smoking.

Results
We identified 15,939 pregnancies with appendectomy, 12,869 pregnancies with cholecystectomy and 19,330 pregnancies with diagnostic laparoscopy. The absolute risk of small for gestational age was 2.2% for patients with appendectomy 0–11 months before last menstrual period, 3.2% 12–23 months before compared with 2.2% when appendectomy was conducted more than 24 months before (adjusted OR 0.95 (95% CI; 0.65 to 1.31) and 1.37(95% CI;1.00 to 1.86). For early preterm birth, the absolute risks were 0.7, 0.5 and 0.8%, for late preterm birth 4.8, 4.4 and 4.7% and for miscarriage 5.7, 6.2 and 5.4%.We observed similar results for cholecystectomy. For diagnostic laparoscopy 0–11 months before pregnancy we found increased risks of small for gestational age (4.0, 2.8 and 2.6%) and late preterm birth (5.9, 5.0 and 4.8%).

Conclusions
We found no increased risk of adverse birth outcomes among pregnancies with appendectomy or cholecystectomy conducted within 2 years before pregnancy compared to more than 2 years before pregnancy. The increased risks 0–11 months after diagnostic laparoscopy are likely explained by confounding by underlying indication. It appears safe to become pregnant any time following appendectomy and cholecystectomy, but, probably depending on indication, attention should be payed 0–11 months after diagnostic laparoscopy.
Mental health symptoms and their relations with dietary diversity and nutritional status among mothers of young children in eastern Democratic Republic of the Congo
Authors: Emerson Jillian A. , Caulfield Laura E. , Kishimata Espoir Musafiri , Nzanzu Jean-Pierre , Doocy Shannon 
Published: February 2020

Abstract
Background
In developing countries, maternal mental health problems have been linked to sub-optimal child feeding practices and child underweight and stunting, but little is known about how maternal mental health is associated with mothers’ own diets and nutritional status. The objective of the study was to investigate the association between mental health symptoms and diet and nutritional status of mothers of young children in South Kivu, DR Congo.

Methods
Participants were 828 mothers of young children enrolled in a larger, quasi-experimental study evaluating a multi-year food security and nutrition project. The present analysis was conducted with cross-sectional data collected from 2015 to 2016. We assessed symptoms of anxiety and depression using the Hopkins Symptom Checklist-25 (HSCL-25) and post-traumatic stress disorder (PTSD) with the Harvard Trauma Questionnaire (HTQ), using a four-point Likert scale. Mean scale scores were calculated ranging from one to four. A variable was created for high distress (participants scoring in the upper quartile of both measures). Dietary diversity scores were calculated from the number of food groups (range zero to ten) consumed the previous day, identified from an open recall. Nutritional status was measured by body mass index (BMI) and underweight (BMI < 18.5 kg/m2, or mid-upper arm circumference < 23 cm for pregnant women). Bivariate and multivariate (adjusting for parent study intervention group, education, age, health, parity, livelihoods zone, and territory of origin) regression analyses were conducted.

Results
Maternal mental health measures were positively and statistically significantly associated with higher dietary diversity scores in adjusted analyses (HSCL-25: ß= 0.18, p = 0.002, HTQ: ß= 0.12, p = 0.029, High Distress: ß= 0.47, p < 0.001). Mental health symptoms were not significantly associated with BMI (HSCL-25: ß = − 0.04, p = 0.824; HTQ: ß = 0.02, p = 0.913; High distress: ß= − 0.02, p = 0.938) or underweight (HSCL 25: OR = 0.91, p = 0.640; HTQ: OR = 1.03, p = 0.866; High distress: OR = 0.78, p = 0.489).

Conclusions
More severe maternal mental health symptoms were associated with higher dietary diversity but not nutritional status, and the reasons for these findings are not clear from available data. More research is needed to identify underlying factors that could influence mental health symptomatology and diet quality among food insecure and extremely resource-limited populations.