bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNA circ_0001459 accelerates hepatocellular carcinoma progression via the miR‐6165/IGF1R axis
Authors: Shen Duo , Zhao Hongyu , Zeng Peng , Ge Meiling , Shrestha Sachinmulmi , Zhao Wei 
Published: February 2022

AbstractAn increasing amount of evidence shows that circular RNAs (circRNAs) have critical effects on cancer progression and development; however, the biological function and potential molecular mechanism of circRNAs in hepatocellular carcinoma (HCC) are still unclear. CircRNA sequencing was used to identify differentially expressed circRNAs between HCC tissue and adjacent normal tissue. We found that circ_0001459 expression was significantly elevated in HCC tissue and cell lines. Furthermore, in vitro and in vivo functional experiments were carried out to detect the effects of circ_0001459 on HCC growth and metastasis. Knockdown of circ_0001459 significantly inhibited the proliferation, migration, and invasion of HCC cells, whereas upregulation of circ_0001459 had the opposite effect. Moreover, bioinformatics analysis, dual‐luciferase reporter assay, RNA immunoprecipitation, and fluorescence in situ hybridization assays were used to predict and verify the interaction between circ_0001459, miR‐6165, and the target gene IGF1R. Downregulation of circ_0001459 decreased IGF1R expression and inhibited epithelial‐to‐mesenchymal transition, which could be rescued by treatment with a miR‐6165 inhibitor. Mechanistically, we revealed that circ_0001459 could sponge miR‐6165 and induce the upregulation of its downstream target IGF1R, thus significantly promoting the progression of HCC. Therefore, circ_0001459 could be a new potential therapeutic target for HCC patients.
Tubular dentin formation by TGF‐β/BMP signaling in dental epithelial cells
Authors: Lee Yoon Seon , Park Yeoung‐Hyun , Seo You‐Mi , Lee Hye‐Kyung , Park Joo‐Cheol 
Published: February 2022

AbstractObjectivesThis study aimed to identify formation of tubular dentin induced by transforming growth factor‐β (TGF‐β) and bone morphogenic protein (BMP) signaling pathway in dental epithelial cells.MethodsWe collected conditioned medium (CM) of rTGF‐β1/rBMP‐2‐treated HAT‐7 and treated to MDPC‐23 cells. The expression levels of odontoblast differentiation markers, KLF4, DMP1, and DSP were evaluated by real‐time PCR and Western blot analysis. To evaluate whether CM of rTGF‐β1/rBMP‐2 induces tubular dentin formation, we made a beagle dog tooth defect model.ResultsHere, we show that Cpne7 is regulated by Smad4‐dependent TGF‐β1/BMP2 signaling pathway in dental epithelial cells. CM of rTGF‐β1/rBMP‐2 treated HAT‐7 or rCPNE7 raises the expression levels of KLF4, DMP1, and DSP in MDPC‐23 cells. When rTGF‐β1 or rBMP‐2 is directly treated to MDPC‐23 cells, however, expression levels of Cpne7‐regulated genes remain unchanged. In a beagle dog defect model, application of rTGF‐β1/BMP2‐treated CM resulted in tubular tertiary dentin mixed with osteodentin at cavity‐prepared sites, while rTGF‐β1 group exhibited homogenous osteodentin.ConclusionsTaken together, Smad4‐dependent TGF‐β1/BMP2 signaling regulates Cpne7 in dental epithelial cells, and CPNE7 protein secreted from pre‐ameloblasts mediates odontoblast differentiation via epithelial–mesenchymal interaction.
Factors associated with overwork among pediatricians at Japanese hospitals
Authors: Ishikawa Masatoshi 
Published: February 2022

AbstractBackgroundGiven the global health issue of doctors working excessive hours, working practices for doctors in Japan are currently undergoing reform. We aimed to ascertain the actual situation of excessive working hours among pediatricians and factors influencing these conditions in Japan.MethodsPediatricians employed at hospitals throughout Japan completed a questionnaire regarding their current working situation, including the time spent at the hospital and whether their working environment had improved since 2018, when the reform of doctors’ working practices began. Multiple logistic regression analysis was performed to identify background factors associated with excessive working hours.ResultsQuestionnaires were sent to 848 Japanese hospitals that submitted insurance reimbursement claims for pediatric inpatient treatment. Valid responses were received from 1,539 pediatricians at 416 hospitals (49% response rate). Of these pediatricians, 51.7% spent ≥60 h/week at their hospital, 14.4% spent ≥80 h/week, and 47.4% worked nights at least four times a month. Compared with 2018, 8.8% and 35.4% responded that their working environment had greatly or somewhat improved, respectively. Working for ≤60 h/week was considered appropriate by 81.9% of pediatricians. Background factors associated with spending ≥80 h/week at the hospital were male sex, age <30 years, lack of children, specialty of pediatric cardiology, annual income exceeding ¥16 million, employment at a private university hospital, and employment at a hospital with a comparatively large number of pediatricians.ConclusionsThis study clarified the background factors and the actual situation of the long working hours among pediatricians working in Japanese hospitals.
Reassessing evidence of Moon–Earth dynamics from tidal bundles at 3.2 Ga (Moodies Group, Barberton Greenstone Belt, South Africa)
Authors: Heubeck Christoph , Bläsing Saskia , Drabon Nadja , Eulenfeld Tom , Grund Marc Ulrich , Homann Martin , Janse Van Rensburg Deon , Köhler Inga , Nabhan Sami , Rabethge Carolin , Voigt Thomas , Zentner‐Joerges Danielle 
Published: February 2022

AbstractPast orbital parameters of the Moon are difficult to reconstruct from geological records because relevant data sets of tidal strata are scarce or incomplete. The sole Archean data point is from the Moodies Group (ca 3.22 Ga) of the Barberton Greenstone Belt, South Africa. From the time‐series analysis of tidal bundles from a well‐exposed subaqueous sand wave of this unit, Eriksson and Simpson (Geology, 28, 831) suggested that the Moon’s anomalistic month at 3.2 Ga was closer to 20 days than the present 27.5 days. This is in apparent accordance with models of orbital mechanics which place the Archean Moon in a closer orbit with a shorter period, resulting in stronger tidal action. Although this study’s detailed geological mapping and section measuring of the site confirmed that the sandstone bed in question is likely a migrating dune, the presence of angular mud clasts, channel‐margin slumps, laterally aggrading channel fills and bidirectional paleocurrents in overlying and underlying beds suggests that this bedform was likely located in a nearshore channel near lower‐intertidal flats and subtidal estuarine bars; it thus carries risk of incomplete preservation. Repeated measurements of foreset thicknesses along the published traverse, measured perpendicular to bedding, failed to show consistent spectral peaks. Larger data sets acquired along traverses measured parallel to bedding along the 20.5 m wide exposure are affected by minor faulting, uneven outcrop weathering, changing illumination, weather, observer bias and show a low reproducibility. The most robust measurements herein confirm the periodicity peak of approximately 14 in the original data of Eriksson and Simpson (Geology, 28, 831). Because laminae may have been eroded, the measurements may represent a lower bound of about 28 lunar days per synodic month. This estimate agrees well with Earth–Moon dynamic models which consider the conservation of angular momentum and place the Archaean Moon in a lower orbit around a faster‐spinning Earth.
Minimally invasive video‐assisted parathyroidectomy in dogs: Technique description and feasibility study
Authors: Sumner Julia P. , Espinheira Gomes Filipe N. C. M. , Flanders James A. 
Published: February 2022

AbstractObjectiveTo describe a minimally invasive approach to the parathyroid gland for the treatment of primary hyperparathyroidism.Study designSurgical technique description and clinical case report.AnimalsFive canine cadavers and 5 client‐owned dogs with primary hyperparathyroidism.MethodsA surgical technique for minimally invasive video‐assisted parathyroidectomy (MIVAP), described for humans, was adapted for dogs. With the dog in dorsal recumbency, a 15 mm incision was made on the midline, 1 finger width caudal to the cricoid cartilage of the larynx. A 5 mm 30° rigid endoscope was inserted into the peritracheal space with the aid of a blunt suction dissector, and fine elevators. The parathyroid was subsequently removed using electrocautery and blunt and sharp dissection. The technique was refined in 5 cadaver dogs to assess feasibility, and was subsequently performed in 5 clinical cases.ResultsA minimally invasive approach to the parathyroid gland was possible and allowed successful removal of a parathyroid mass in 5 dogs without complication. The use of fluid ingress was trialed in 1 cadaver and not found to be helpful. The use of a blunt suction dissector greatly facilitated dissection of the peritracheal space.ConclusionMinimally invasive video‐assisted parathyroidectomy is feasible in dogs and was not associated with complications in 5 clinical cases.Clinical significanceMinimally invasive techniques tend to reduce morbidity and are popular with pet owners. This study demonstrates that a minimally invasive technique may be considered for parathyroidectomy in dogs.
Implementation of Soft Computing Techniques in Predicting and Optimizing the Operating Parameters of Compression Ignition Diesel Engines: State-of-the-Art Review, Challenges, and Future Outlook
Authors: More Shubham M. , Kakati Jyotirmoy , Pal Sukhomay , Saha Ujjwal K. 
Published: February 2022

Abstract
Fossil fuels being the primary source of energy to global industrialization and rapid development are being consumed at an alarming rate, thus creating a dire need to search for alternative fuels and optimize the internal combustion (IC) engine performance parameters. Traditional methods of testing and optimizing the performances of IC engines are complex, time consuming, and expensive. This has led the researchers to shift their focus to faster and inexpensive techniques like soft computing (SC), which predict the optimum performance with a substantial accuracy. The SC techniques commonly used are artificial neural network (ANN), fuzzy logic, adaptive neuro-fuzzy inference system (ANFIS), genetic algorithm (GA), particle swarm optimization (PSO), and hybrid techniques like ANN-GA, ANN-PSO, and others. The data of engine parameters predicted with these models have been found to be in very close indices with the experimented values making them a reliable predicting tool. The ANN, fuzzy logic, and ANFIS models have been found to have a correlation coefficient (R) above 0.9 suggesting a good level of agreement between experimented and predicted values of several engine-out parameters. In the present review article, the application of various SC techniques in the prediction and the optimization of output parameters of compression ignition (CI) diesel engines are thoroughly reviewed along with their future prospects and challenges. This review work highlights the implication of these SC techniques in CI diesel engines run on both conventional fuel as well as biodiesels.
Recent trends in high-volume Medicare stroke thrombectomy provider characteristics
Authors: Jayaraman Keshav , Santavicca Stefan , Hughes Danny R , Hirsch Joshua A , Duszak, Richard , Chatterjee Arindam R 
Published: February 2022

BackgroundIntracranial mechanical thrombectomy (MT) is increasingly indicated for use in acute ischemic stroke patients. We analyzed recent trends in the characteristics and geographic distributions of physicians providing this service with frequency to Medicare beneficiaries.MethodsWe linked public data sources to elucidate and visualize trends in high-volume MT providers between 2016 and 2019.ResultsHigh-volume MT providers increased by 184% between 2016 and 2019. The number of neurosurgeons, neurologists, and radiologists in this physician population increased by 251%, 205%, and 139%, respectively. Male practitioners accounted for 96% of providers in the most recent year of analysis. International medical graduates accounted for roughly one-third of these physicians across all 4 years of analysis. As of 2019, the three states with the most high-volume MT providers were Florida, California, and Texas, accounting for 7%, 7%, and 6% of providers, respectively.ConclusionsHigh-volume providers of MT services for Medicare beneficiaries represent a dynamic and rapidly expanding subset of physicians with diverse specialty backgrounds.
Mitochondria-targeted antioxidant supplementation does not affect muscle soreness or recovery of maximal voluntary isometric contraction force following muscle-damaging exercise in untrained men: a randomized clinical trial
Authors: Broome S.C. , Atiola R.D. , Braakhuis A.J. , Mitchell C.J. , Merry T.L. 
Published: February 2022

Unaccustomed exercise causes muscle damage resulting in loss of muscle function, which may be attributable to exercise-induced increases in skeletal muscle reactive oxygen species. This study examined the effect of mitochondria-targeted antioxidant supplementation on recovery of muscle function following exercise. Thirty-two untrained men received MitoQ (20 mg/day) or a placebo for 14 days before performing 300 maximal eccentric contractions of the knee extensor muscles of 1 leg. Muscle function was assessed using isokinetic dynamometry before, immediately after, and 24, 48, 72, and 168 hours after exercise. Muscle soreness was assessed using a visual analogue scale 24, 48, 72, and 168 hours after exercise. Blood samples were collected before, immediately after, and 2, 24, 48, 72, and 168 hours after exercise and urine samples were collected before and during the 48 hours after exercise. The reduction in maximal voluntary isometric contraction force and peak concentric torque following exercise was unaffected by MitoQ while recovery of peak eccentric torque was delayed in the MitoQ group. Exercise-induced increases in urine F2-isoprostanes were unaffected by MitoQ. MitoQ augmented exercise-induced increases in plasma creatine kinase levels, while plasma IL-6 was similar between groups. Muscle soreness was not affected by MitoQ. These results indicate that MitoQ does not attenuate post-exercise muscle soreness and may delay recovery of muscle function following eccentric exercise. Trial registration number: ACTRN12620001089921. Novelty: Post-exercise recovery of maximal voluntary isometric contraction force and peak concentric torque were unaffected by MitoQ. MitoQ delayed post-exercise recovery of peak eccentric torque. Post-exercise muscle soreness was unaffected by MitoQ.
Warped vacuum energy by black holes
Authors: Ovalle J. 
Published: February 2022

AbstractThe belief still persists, at least for an important part of the community, that in general relativity the cosmological constant $$\Lambda $$
Λ
must remain immaculate. However, Bianchi identities show that $$\Lambda $$
Λ
could acquire local properties in the presence of matter, i.e., $$\Lambda \rightarrow \,\Lambda (x^\mu )$$

Λ
→

Λ
(

x
μ

)

. In this paper we go even further, and we show that a non-uniform vacuum energy does not even require coexistence with any additional form of matter-energy, nor of any theory beyond general relativity, at least for extreme environments, such as the proximity of a black hole.
YAP and TAZ in Vascular Smooth Muscle Confer Protection Against Hypertensive Vasculopathy
Authors: Daoud Fatima , Arévalo Martinez Marycarmen , Holmberg Johan , Alajbegovic Azra , Ali Neserin , Rippe Catarina , Swärd Karl , Albinsson Sebastian 
Published: February 2022

Background:
Hypertension remains a major risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. We hypothesize that appropriate mechanotransduction and contractile function in vascular smooth muscle cells are crucial to maintain vascular wall integrity. The Hippo pathway effectors YAP (yes-associated protein 1) and TAZ (WW domain containing transcription regulator 1) have been identified as mechanosensitive transcriptional coactivators. However, their role in vascular smooth muscle cell mechanotransduction has not been investigated in vivo.

Methods:
We performed physiological and molecular analyses utilizing an inducible smooth muscle–specific YAP/TAZ knockout mouse model.

Results:
Arteries lacking YAP/TAZ have reduced agonist-mediated contraction, decreased myogenic response, and attenuated stretch-induced transcriptional regulation of smooth muscle markers. Moreover, in established hypertension, YAP/TAZ knockout results in severe vascular lesions in small mesenteric arteries characterized by neointimal hyperplasia, elastin degradation, and adventitial thickening.

Conclusions:
This study demonstrates a protective role of YAP/TAZ against hypertensive vasculopathy.
Deletion of BACH1 Attenuates Atherosclerosis by Reducing Endothelial Inflammation
Authors: Jia Mengping , Li Qinhan , Guo Jieyu , Shi Weihao , Zhu Lei , Huang Yijun , Li Yongbo , Wang Li , Ma Siyu , Zhuang Tao , Wang Xiaoqun , Pan Qi , Wei Xiangxiang , Qin Yue , Li Xiaobo , Jin Jiayu , Zhi Xiuling , Tang Jingdong , Jing Qing , Li Shanqun , Jiang Lindi , Qu Lefeng , Osto Elena , Zhang Jianyi , Wang Xinhong , Yu Bo , Meng Dan 
Published: February 2022

Background:
The transcription factor BACH1 (BTB and CNC homology 1) suppressed endothelial cells (ECs) proliferation and migration and impaired angiogenesis in the ischemic hindlimbs of adult mice. However, the role and underlying mechanisms of BACH1 in atherosclerosis remain unclear.

Methods:
Mouse models of atherosclerosis in endothelial cell (EC)-specific-Bach1 knockout mice were used to study the role of BACH1 in the regulation of atherogenesis and the underlying mechanisms.

Results:
Genetic analyses revealed that coronary artery disease-associated risk variant rs2832227 was associated with BACH1 gene expression in carotid plaques from patients. BACH1 was upregulated in ECs of human and mouse atherosclerotic plaques. Endothelial Bach1 deficiency decreased turbulent blood flow- or western diet-induced atherosclerotic lesions, macrophage content in plaques, expression of endothelial adhesion molecules (ICAM1 [intercellular cell adhesion molecule-1] and VCAM1 [vascular cell adhesion molecule-1]), and reduced plasma TNF-α (tumor necrosis factor-α) and IL-1β levels in atherosclerotic mice. BACH1 deletion or knockdown inhibited monocyte–endothelial adhesion and reduced oscillatory shear stress or TNF-α-mediated induction of endothelial adhesion molecules and/or proinflammatory cytokines in mouse ECs, human umbilical vein ECs, and human aortic ECs. Mechanistic studies showed that upon oscillatory shear stress or TNF-α stimulation, BACH1 and YAP (yes-associated protein) were induced and translocated into the nucleus in ECs. BACH1 upregulated YAP expression by binding to the YAP promoter. BACH1 formed a complex with YAP inducing the transcription of adhesion molecules. YAP overexpression in ECs counteracted the antiatherosclerotic effect mediated by Bach1-deletion in mice. Rosuvastatin inhibited BACH1 expression by upregulating microRNA let-7a in ECs, and decreased Bach1 expression in the vascular endothelium of hyperlipidemic mice. BACH1 was colocalized with YAP, and the expression of BACH1 was positively correlated with YAP and proinflammatory genes, as well as adhesion molecules in human atherosclerotic plaques.

Conclusions:
These data identify BACH1 as a mechanosensor of hemodynamic stress and reveal that the BACH1-YAP transcriptional network is essential to vascular inflammation and atherogenesis. BACH1 shows potential as a novel therapeutic target in atherosclerosis.
Hypertension and Ventricular–Arterial Uncoupling in Collegiate American Football Athletes
Authors: Tso Jason V. , Turner Casey G. , Liu Chang , Ahmad Syed , Ali Abbas , Selvaraj Steve , Galante Angelo , Gilson Carla R. , Clark Craig , Williams B. Robinson , Quyyumi Arshed A. , Baggish Aaron L. , Kim Jonathan H. 
Published: February 2022

Background
Ventricular–arterial (VA) coupling is defined as the ratio between arterial elastance (EA) and left ventricular elastance (ELV). VA uncoupling, as occurs in hypertensive heart disease, is associated with adverse outcomes. This study sought to determine the relationship between American football (AF)–associated hypertension and VA uncoupling.

Methods and Results

This was a multicenter, longitudinal, and repeated measures observational study of collegiate AF athletes across 3 years of AF participation. Of 200 freshman athletes initially enrolled, 142 (67 Black [47%]/75 White [53%], 58 linemen [41%]/84 nonlinemen [59%]) were prospectively studied with echocardiography and applanation tonometry. Primary echocardiographic VA coupling outcome measures were EA/ELV and ΔEA/ELV, with increased EA/ELV indicating VA uncoupling. Adjusting for race and player position, AF athletes demonstrated increased EA/ELV (mean [95% CI]Δ, 0.10 [0.04–0.15];
P
=0.001) and systolic blood pressure (SBP) (mean [95% CI]Δ, 11.4 [8.3–14.5] mm Hg,
P
<0.001) over their collegiate AF careers. In combination with longitudinal VA uncoupling, hypertension prevalence (including both stage 1 and 2) increased from 54% at baseline to 77% (44% stage 2) at the end of the study period (
P
<0.001). In multivariable mixed‐effects linear regression analysis, higher SBP (β=0.021,
P
=0.02), lower E′ (β=−0.010,
P
=0.03), and worse global longitudinal strain (β=0.036,
P
<0.001) were associated with higher EA/ELV. Increased SBP (ΔSBP, β=0.029,
P
=0.02) and worsened global longitudinal strain (Δglobal longitudinal strain, β=0.045,
P
<0.001) also predicted increased ΔEA/ELV.

Conclusions
VA uncoupling is associated with pathologically increased SBP and subclinical impairments in left ventricular systolic function in collegiate AF athletes, indicating a key mechanism underlying maladaptive cardiovascular phenotypes observed in this population. Future studies analyzing whether targeted clinical interventions improve VA coupling and health outcomes are warranted.
Turkish EFL learners’ interpretation of metaphors
Authors: Kökcü Şeyma , Ortaçtepe Hart Deniz 
Published: February 2022

Abstract
This study investigated Turkish EFL learners’ conceptual socialization in terms of their interpretation of English metaphors in three categories; a) conceptually and linguistically similar, b) conceptually similar, linguistically different, and c) conceptually and linguistically different metaphors. Data were collected through sentence level and situation-based tests. Learners’ responses were analyzed by comparing them to the native English speakers’ (NES s). Findings indicated that Turkish EFL learners could only benefit from the situational information when the metaphors were either conceptually or linguistically similar, and their performance differed very much from NES s in terms of correct interpretation of the metaphors. These results underline EFL learners’ lack of exposure to target culture and interaction with native speakers and thus the importance of non-native English speaking teachers (NNEST s) in EFL contexts as the most valuable source of the target language conceptual system.