bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of a genetic variation in the microRNA-4421 binding site of ERP29 regarding risk of oropharynx cancer and prognosis
Authors: Carron Juliana , Costa Ana Paula Dalla , Rinck-Junior José Augusto , Mariano Fernanda Viviane , de Sá Carvalho Benilton , Lima Carmen Silvia Passos , Lourenço Gustavo Jacob 
Published: October 2020

AbstractWe conducted a two-stage association study on patients with oropharynx (OP) squamous cell carcinoma (SCC) and healthy controls to identify single nucleotide variants (SNVs) located at the microRNA (miR)-binding sites of carcinogenesis genes associated with risk and prognosis of the disease. In stage 1, 49 patients and 49 controls were analyzed using Genome-Wide Human SNV Arrays to identify variants in the 3′-untranslated region (3′-UTR) of carcinogenesis-related genes, and one SNV was selected for data validation in stage 2 by TaqMan assays in 250 OPSCC patients and 250 controls. TheERP29c.*293A > G (rs7114) SNV located at miR-4421 binding site was selected for data validation among 46 SNVs. The ERp29 and miR-4421 levels were evaluated by quantitative-PCR and Western blotting. Interaction between miR-4421 with 3′-UTR ofERP29was evaluated by luciferase reporter assay. Event-free survival (EFS) was calculated by Kaplan–Meier and Cox methods.ERP29GG variant genotype was more common in OPSCC patients than in controls (6.4%vs3.6%,p = 0.02; odds ratio: 5.67; 95% confidence interval (CI) 1.27–25.26). Shorter EFS were seen in the base of tongue (BT) SCC patients with GG genotype (0.0%vs36.2%,p = 0.01; hazard ratio: 2.31; 95% CI: 1.03–5.15). Individuals withERP29AG or GG genotypes featured lower levels ofERP29mRNA (p = 0.005), ERp29 protein (p < 0.001) and higher levels of miR-4421 (p = 0.02). The miR-4421 showed more efficient binding with 3′-UTR of the variant G allele when compared with wild-type allele A (p = 0.001). Our data suggest thatERP29rs7114 SNV may alter the risk and prognosis of OPSCC due to variation in the ERp29 production possibly modulated by miR-4421.
A de novo frameshift mutation in ZEB2 causes polledness, abnormal skull shape, small body stature and subfertility in Fleckvieh cattle
Authors: Gehrke Lilian J. , Upadhyay Maulik , Heidrich Kristin , Kunz Elisabeth , Klaus-Halla Daniela , Weber Frank , Zerbe Holm , Seichter Doris , Graf Alexander , Krebs Stefan , Blum Helmut , Capitan Aurélien , Thaller Georg , Medugorac Ivica 
Published: October 2020

AbstractPolledness in cattle is an autosomal dominant trait. Previous studies have revealed allelic heterogeneity at thepolledlocus and four different variants were identified, all in intergenic regions. In this study, we report a case of polled bull (FV-Polled1) born to horned parents, indicating a de novo origin of this polled condition. Using 50K genotyping and whole genome sequencing data, we identified on chromosome 2 an 11-bp deletion (AC_000159.1:g.52364063_52364073del;Del11) in the second exon ofZEB2gene as the causal mutation for this de novo polled condition. We predicted that the deletion would shorten the protein product ofZEB2by almost 91%. Moreover, we showed that all animals carryingDel11mutation displayed symptoms similar to Mowat-Wilson syndrome (MWS) in humans, which is also associated with genetic variations inZEB2. The symptoms in cattle include delayed maturity, small body stature and abnormal shape of skull. This is the first report of a de novo dominant mutation affecting onlyZEB2and associated with a genetic absence of horns. Therefore our results demonstrate undoubtedly thatZEB2plays an important role in the process of horn ontogenesis as well as in the regulation of overall development and growth of animals.
Effects of olanzapine treatment on lipid profiles in patients with schizophrenia: a systematic review and meta-analysis
Authors: Li Rong , Zhang Yiqi , Zhu Wenqiang , Ding Chen , Dai Wenjie , Su Xin , Dai Wen , Xiao Jingmei , Xing Zhenhua , Huang Xiansheng 
Published: October 2020

AbstractOlanzapine-induced dyslipidemia significantly increases the risk of cardiovascular disease in patients with schizophrenia. However, the clinical features of olanzapine-induced dyslipidemia remain hitherto unclear because of inconsistencies in the literature. This meta-analysis thus investigated the effects of olanzapine treatment on lipid profiles among patients with schizophrenia. Studies of the effects of olanzapine on lipids were obtained through the PubMed, Web of science, The Cochrane Library and Embase databases (up to January 1, 2020). Twenty-one studies and 1790 schizophrenia patients who received olanzapine therapy were included in our analysis. An olanzapine-induced increase was observed in plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels in patients with schizophrenia (all P < 0.05). Moreover, the time points analyzed included the following: baseline, 4 weeks, 6 weeks, 8 weeks, 12 weeks, and ≥ 24 weeks (data of ≥ 24 weeks were integrated). The significant elevation of TG, TC, and LDL-C was observed in patients with schizophrenia already by 4 weeks of olanzapine therapy (all P < 0.05), with no obvious changes observed in high-density lipoprotein cholesterol (HDL-C) (P > 0.05). In conclusion, olanzapine-induced dyslipidemia, characterized by increased TG, TC, and LDL-C levels, was observed in patients with schizophrenia already by 4 weeks of olanzapine treatment.
Inhibition of O-GlcNAc transferase activates tumor-suppressor gene expression in tamoxifen-resistant breast cancer cells
Authors: Barkovskaya Anna , Seip Kotryna , Prasmickaite Lina , Mills Ian G. , Moestue Siver A. , Itkonen Harri M. 
Published: October 2020

AbstractIn this study, we probed the importance of O-GlcNAc transferase (OGT) activity for the survival of tamoxifen-sensitive (TamS) and tamoxifen-resistant (TamR) breast cancer cells. Tamoxifen is an antagonist of estrogen receptor (ERα), a transcription factor expressed in over 50% of breast cancers. ERα-positive breast cancers are successfully treated with tamoxifen; however, a significant number of patients develop tamoxifen-resistant disease. We show that in vitro development of tamoxifen-resistance is associated with increased sensitivity to the OGT small molecule inhibitor OSMI-1. Global transcriptome profiling revealed that TamS cells adapt to OSMI-1 treatment by increasing the expression of histone genes. This is known to mediate chromatin compaction. In contrast, TamR cells respond to OGT inhibition by activating the unfolded protein response and by significantly increasing ERRFI1 expression. ERRFI1 is an endogenous inhibitor of ERBB-signaling, which is a known driver of tamoxifen-resistance. We show that ERRFI1 is selectively downregulated in ERα-positive breast cancers and breast cancers driven by ERBB2. This likely occurs via promoter methylation. Finally, we show that increased ERRFI1 expression is associated with extended survival in patients with ERα-positive tumors (p = 9.2e−8). In summary, we show that tamoxifen-resistance is associated with sensitivity to OSMI-1, and propose that this is explained in part through an epigenetic activation of the tumor-suppressor ERRFI1 in response to OSMI-1 treatment.
Observational learning of fear in real time procedure
Authors: Szczepanik Michał , Kaźmierowska Anna M. , Michałowski Jarosław M. , Wypych Marek , Olsson Andreas , Knapska Ewelina 
Published: October 2020

AbstractLearning to avoid threats often occurs by observing others. Most previous research on observational fear learning (OFL) in humans has used pre-recorded standardized video of an actor and thus lacked ecological validity. Here, we aimed to enhance ecological validity of the OFL by engaging participants in a real-time observational procedure (35 pairs of healthy male friends, age 18–27). One of the participants watched the other undergo a differential fear conditioning task, in which a conditioned stimulus (CS+) was paired with an aversive electric shock and another stimulus (CS−) was always safe. Subsequently, the CS+ and CS− were presented to the observer to test the OFL. While the friend’s reactions to the shock elicited strong skin conductance responses (SCR) in all observers, subsequent differential SCRs (CS+ > CS−) were found only when declarative knowledge of the CS+/US contingency (rated by the participants) was acquired. Contingency-aware observers also showed elevated fear potentiated startle responses during both CS+ and CS− compared to baseline. We conclude that our real-time procedure can be effectively used to study OFL. The procedure allowed for dissecting two components of the OFL: an automatic emotional reaction to the response of the demonstrator and learning about stimulus contingency.
Neopterin and biopterin levels and tryptophan degradation in patients with diabetes
Authors: Gürcü Sinem , Girgin Gözde , Yorulmaz Göknur , Kılıçarslan Bilge , Efe Belgin , Baydar Terken 
Published: October 2020

AbstractThis study aimed to evaluate the possible changes of neopterin, biopterin levels and tryptophan degradation in diabetes and to compare the results within diabetes groups and with healthy subjects. Diabetes mellitus patients and healthy controls were recruited the study. Patients were further subgrouped according to their drug therapy. Serum neopterin concentrations were detected by ELISA. Urinary neopterin, biopterin, serum tryptophan (Trp) and kynurenine (Kyn) levels were detected by HPLC. There was no difference between controls and diabetes patients in serum neopterin, urinary neopterin and biopterin levels (p > 0.05, all). Serum Trp and Kyn levels were significantly different in type 1 diabetes (T1DM) patients compared to controls (p < 0.05, both). Serum neopterin levels were significantly higher in type 2 diabetes patients (T2DM) compared to T1DM (p < 0.05). Urinary biopterin levels of T2DM patients using both metformin and vildagliptin were significantly higher than T1DM patients (p < 0.05). The correlations between serum neopterin and urinary neopterin, Kyn and Kyn/Trp were statistically significant in control and patient groups (p < 0.05, all). The study showed that Kyn/Trp was altered in diabetes patients due to immune modulation. On the other hand, although xenobiotic exposure may change pteridine levels, metformin and/or vildagliptin use in T2DM patients did not have any effect on the measured parameters.
Nosema ceranae causes cellular immunosuppression and interacts with thiamethoxam to increase mortality in the stingless bee Melipona colimana
Authors: Macías-Macías José O. , Tapia-Rivera José C. , De la Mora Alvaro , Tapia-González José M. , Contreras-Escareño Francisca , Petukhova Tatiana , Morfin Nuria , Guzman-Novoa Ernesto 
Published: October 2020

AbstractThe microsporidian parasite Nosema ceranae and neonicotinoid insecticides affect the health of honey bees (Apis mellifera). However, there is limited information about the effect of these stressors on other pollinators such as stingless bees (Hymenoptera: Meliponini). We examined the separate and combined effects of N. ceranae and the neonicotinoid thiamethoxam at field-exposure levels on the survivorship and cellular immunity (hemocyte concentration) of the stingless bee Melipona colimana. Newly-emerged bees were subjected to four treatments provided in sucrose syrup: N. ceranae spores, thiamethoxam, thiamethoxam and N. ceranae, and control (bees receiving only syrup). N. ceranae developed infections of > 467,000 spores/bee in the group treated with spores only. However, in the bees subjected to both stressors, infections were < 143,000 spores/bee, likely due to an inhibitory effect of thiamethoxam on the microsporidium. N. ceranae infections did not affect bee survivorship, but thiamethoxam plus N. ceranae significantly increased mortality. Hemocyte counts were significantly lower in N. ceranae infected-bees than in the other treatments. These results suggest that N. ceranae may infect, proliferate and cause cellular immunosuppression in stingless bees, that exposure to sublethal thiamethoxam concentrations is toxic to M. colimana when infected with N. ceranae, and that thiamethoxam restrains N. ceranae proliferation. These findings have implications on pollinators’ conservation.
Identification of three molecular subtypes based on immune infiltration in ovarian cancer and its prognostic value
Authors: Liu Juan , Tan Zongjian , He Jun , Jin Tingting , Han Yuanyuan , Hu Li , Song Jukun , Huang Shengwen 
Published: October 2020

Abstract
Background: Increasing studies suggest that tumor immune infiltration is a relative factor of prognosis in ovarian cancer (OvCa). The present study explored the composition of tumor-infiltrating immune cells (TIICs) in OvCa using CIBERSORT algorithm and further assessed their values for prognosis and therapeutic strategies by molecular subtypes.
Methods: Publicly available databases including The Cancer Genome Atlas (TCGA) and GTEx were searched. Ovarian tumor samples were available from TCGA, and normal ovarian samples were obtained from the GTEx dataset. The relative proportions of immune cell profiling in OvCa and normal samples were evaluated by CIBERSORT algorithm. Association between each immune cell subtype and survival was inferred by the fractions of 22 immune cell types. “CancerSubtypes” R-package was employed to identify the three types of molecular classification and analyze the functional enrichment in each subclass. Response to immunotherapy and anticancer drug targets was predicted via TIDE algorithm and GDSC dataset.
Results: Substantial variation reflecting individual difference was identified between cancer and normal tissues in the immune infiltration profiles. T cells CD4 memory activated, macrophages M1 were associated with improved overall survival (OS) as evaluated by univariate Cox regression and multivariate Cox. Three subtypes were identified by ´CancerSubtypes’ R-package and every sub-cluster possessed specific immune cell characterization. Meanwhile, Cluster II exhibited poor prognosis and sensitive response to immunotherapy.
Conclusions: The cellular component of immune infiltration shows remarkable variation in OvCa. Profiling of immune infiltration is useful in prediction of prognosis of OvCa. The results from profiling might be considered in therapeutic modulation.
SiC‐based high‐gain DC–DC converters with fault ride‐through capability
Authors: Gurukumar Gangavarapu , Sai Krishna M.V. , Sundaramoorthy Kumaravel , Babaei Ebrahim 
Published: October 2020

This study presents active switched passive network‐based high‐gain DC–DC converters. The active switched network is formulated using two inductors, one capacitor and two diodes. Hence, the network is named as a 2L–C–2D network. Using ten components, an asymmetric high‐gain DC‐DC converter is proposed. This converter achieves a gain of 29 at an 80% duty ratio. In the asymmetric converter structure by replacing the inductor by another 2L–C–2D network, the symmetric converter structure is proposed using 14 components. This converter structure achieves the gain of 49 at the same 80% duty ratio. Apart from increasing the voltage gain, the 2L–C–2D network helps to reduce the voltage and current stresses of the converter. The utilisation of two semiconductor switches in the proposed converter structures permits a fault ride‐through capability even when any one of the switches fails. Operations of the converters in continuous conduction mode (CCM) and discontinuous conduction mode (DCM) are discussed, and the boundary condition between CCM and DCM is derived. To limit the effect of parasitic elements on the converter performance, SiC‐based semiconductor devices are used in the 500 W hardware prototype. The maximum efficiency of 92.8% is achieved in the case of a symmetric converter.
Properties of Novel High Temperature Titanium Alloys for Aerospace Applications
Authors: Mantione John , Garcia-Avila Matias , Arnold Matthew , Bryan David , Foltz John 
Published: October 2020

The attractive combination of strength and low density has resulted in titanium alloys covering 15 to 25% of the weight of a modern jet engine, with titanium currently being used in fan, compressor and nozzle components. Typically, titanium alloys used in jet engine applications are selected from the group of near alpha and alpha-beta titanium alloys, which exhibit superior elevated temperature strength, creep resistance and fatigue life compared to typical titanium alloys such as Ti-6Al-4V. Legacy titanium alloys for elevated temperature jet engine applications include Ti-5Al-2Sn-2Zr-4Mo-4Cr, Ti-6Al-2Sn-4Zr-2Mo-0.1Si and Ti-4Al-4Mo-2Sn-0.5Si. Improving the mechanical behavior of these alloys enables improved component performance, which is crucial to advancing jet engine performance.
As a world leader in supplying advanced alloys of titanium, nickel, cobalt, and specialty stainless steels, ATI is developing new titanium alloys with improved elevated temperature properties. These improved properties derive from precipitation of secondary intermetallics in alpha-beta titanium alloys. ATI has developed several new alpha-beta titanium alloy compositions which exhibit significantly improved elevated temperature strength and creep resistance. This paper will focus on the effects of chemistry and heat treat conditions on the microstructure and resulting elevated temperature properties of these new aerospace titanium alloys.
The Influence of Household Income on Survival following Posterior Fossa Tumor Resection at a Large Academic Medical Center
Authors: Blue Rachel , Detchou Donald K. , Dimentberg Ryan , Shultz Kaitlyn , Spadola Michael , McClintock Scott D. , Malhotra Neil R. 
Published: October 2020

Abstract
Objectives The present study examines the effect of median household income on mid- and long-term outcomes in a posterior fossa brain tumor resection population.
Design This is a retrospective regression analysis.
Setting The study conducted at a single, multihospital, urban academic medical center.
Participants A total of 283 consecutive posterior fossa brain tumor cases, excluding cerebellar pontine angle tumors, over a 6-year period (June 09, 2013–April 26, 2019) was included in this analysis.
Main Outcome Measures Outcomes studied included 90-day readmission, 90-day emergency department evaluation, 90-day return to surgery, reoperation within 90 days after index admission, reoperation throughout the entire follow-up period, mortality within 90 days, and mortality throughout the entire follow-up period. Univariate analysis was conducted for the whole population and between the lowest (Q1) and highest (Q4) socioeconomic quartiles. Stepwise regression was conducted to identify confounding variables.
Results Lower socioeconomic status was found to be correlated with increased mortality within 90 postoperative days and throughout the entire follow-up period. Similarly, analysis between the lowest and highest household income quartiles (Q1 vs. Q4) demonstrated Q4 to have significantly decreased mortality during total follow-up and a decreasing but not significant difference in 90-day mortality. No significant difference in morbidity was observed.
Conclusion This study suggests that lower household income is associated with increased mortality in both the 90-day window and total follow-up period. It is possible that there is an opportunity for health care providers to use socioeconomic status to proactively identify high-risk patients and provide additional resources in the postoperative setting.
Ophthalmology Education in COVID-19: A Remote Elective for Medical Students
Authors: DeVaro Sarah N. , Uner Ogul E. , Khalifa Yousuf M. , Graubart Emily B. 
Published: October 2020

Abstract
Background The novel coronavirus disease (COVID-19) has created obstacles for medical student education, as clinical rotations were temporarily halted. Recent literature shows online electives may provide an alternative learning platform. We developed a teleophthalmology student elective for rising third-year medical student (MS3) and fourth-year medical student (MS4) to continue teaching and exposure to the field.
Methods A 4-week remote elective was approved by Emory University School of Medicine and offered between April 18, 2020, and May 15, 2020, for rising MS3s and MS4s. The curriculum consisted of online self-study materials, student presentations, chart review assignments, case-based discussions with faculty, and telehealth experiences. All students were surveyed and tested with questions from United States Medical Licensing Examination World (UWorld) test bank at the end of the course.
Results A total of 18 students were enrolled, with 66.7% MS3 and 33.3% MS4 participants. The mean rating of fulfillment of course learning objectives was 8.1/10 (range, 6.7–8.8), with mean ratings of 8.2 for MS3s and 7.7 for MS4s. There was a significant increase in self-reported knowledge in ophthalmology, with an increase from 4.6 to 8.1 for MS3s (p = 0.002) and 6.7 to 8.0 for MS4s (p = 0.04). Students also reported higher interest in the field, with an increase from 4.9 to 7.8 for MS3s (p = 0.01) and 7.5 to 8.7 for MS4s (p = 0.1). The students performed significantly higher on the postcourse test (94.8%) than UWorld question bank users (74.1%) (p < 0.001).
Conclusion Our novel ophthalmology elective significantly enhanced self-reported medical student knowledge and interest in the field during a crisis that required transition to remote learning. Further study of student telehealth experience and objective assessment is needed to improve online learning in ophthalmology.
The Longissimus Capitis Insertion as a Superficial Landmark for the Sigmoid Sinus: An Anatomical Study
Authors: Iwanaga Joe , Watanabe Koichi , Khan Pervez A. , Nerva John D. , Amenta Peter S. , Dumont Aaron S. , Tubbs R. Shane 
Published: October 2020

Abstract
Objective Many external anatomical landmarks have been used for approximating deeper, intracranial structures. Herein, we evaluate the attachment of the longissimus capitis (LC) on the mastoid process as a landmark for the underlying sigmoid sinus.
Methods Adult cadavers underwent dissection of the posterior occiput with special attention to the attachment of the LC muscle. Once the periphery of the muscle's tendon of attachment was determined, a burr hole was made in this area and evaluated internally for its relationship to the sigmoid sinus.
Results From an intracranial view, burr holes on all sides were over the sigmoid sinus and just slightly lateral to the center of the sinus. The distance from the midline to the medial border of the insertion of the LC had a mean of 63.0 ± 7.2 mm. The width of the tendon of insertion of the LC on the mastoid process had a mean of 17.6 ± 5.7 mm. The length of the tendon insertion of the LC had a mean of 14.7 ± 4.7 mm. The distance from the inferior border of the insertion of the LC to the tip of the mastoid process had a mean of 6.2 ± 4.5 mm.
Conclusion To our knowledge, use of the attachment site of the LC on the mastoid process as an external landmark for the underlying sigmoid sinus has not previously been reported. Based on our cadaveric findings, the sigmoid sinus is centered under the attachment of the LC regardless of the width of its tendon.