bluuebunny/crossref_metadata_2025_split huggingface dataset:
The enigmatic role of matrix metalloproteinases in epithelial‐to‐mesenchymal transition of oral squamous cell carcinoma: Implications and nutraceutical aspects
Authors: Ricci Serena , Pinto Federica , Auletta Adelaide , Giordano Antonio , Giovane Alfonso , Settembre Giuliana , Boccellino Mariarosaria , Boffo Silvia , Di Carlo Angelina , Di Domenico Marina 
Published: February 2019

AbstractThe most prevalent malignancy in the oral cavity is represented by oral squamous cell carcinoma, an aggressive disease mostly detected in low‐income communities. This neoplasia is mostly diffused in older men particularly exposed to risk factors such as tobacco, alcohol, and a diet rich in fatty foods and poor in vegetables. In oral squamous cell carcinoma, a wide range of matrix‐cleaving proteinases are involved in extracellular matrix remodeling of cancer microenvironment. In particular, matrix metalloproteinases (MMPs) represent the major and most investigated protagonists. Owing to their strong involvement in malignant pathologies, MMPs are considered the most promising new biomarkers in cancer diagnosis and prognosis. The interest in studying MMPs in oral cancer biology is also owing to their prominent role in epithelial‐to‐mesenchymal transition (EMT). EMT is an intricate process involving different complex pathways. EMT‐related proteins are attractive diagnostic biomarkers that characterize the activation of biological events that promote cancer's aggressive expansion. Different antioncogenic natural compounds have been investigated to counteract oral carcinogenesis, with the scope of obtaining better clinical results and lower morbidity. In particular, we describe the role of different nutraceuticals used for the regulation of MMP‐related invasion and proliferation of oral cancer cells.
Generation of Fam83h knockout mice by CRISPR/Cas9‐mediated gene engineering
Authors: Nasseri Sherko , Nikkho Bahram , Parsa Sara , Ebadifar Asghar , Soleimani Farzad , Rahimi Karim , Vahabzadeh Zakaria , Khadem‐Erfan Mohammad Bagher , Rostamzadeh Jalal , Baban Babak , Banafshi Omid , Assadollahi Vahideh , Mirzaie Sako , Fathi Fardin 
Published: February 2019

AbstractFamily with sequence similarity 83 member H (FAM83H) protein‐coding geneplay an essential role in the structural organization, calcification of developing enamel, and keratin cytoskeleton disassembly by recruiting Casein kinase 1 alpha (CSNK1A1) to keratin filaments. In this study, we have applied CRISPR Cas9 nickase (D10A) to knockout (KO) the
Fam83h gene in NMRI outbred mice. We generated homozygous
Fam83h KO mice (
Fam83h
Ko/Ko) through a premature termination codon, which was validated by Sanger sequencing in F0 generation. Next, we also bred the
FAM83H KO for two generations. Reverse‐transcription polymerase chain reaction and Western blot analysis approved the Fam83h KO mice. The
Fam83h KO mice had evidence of normal morphology at the cervical loops, secretory and maturation stages, and mandibular molars. In comparison with the normal wild‐type mice (
Fam83h
W/W), the F2 homozygous KO (
Fam83h
Ko/Ko) had sparse, scruffy coats with small body size and decreased general activity. Also, they had the natural reproductive ability and natural lifespan. In addition, delay in opening the eyes and dry eyes among infant mice were seen. The F1 heterozygous mice looked comparable to the normal wild‐type mice (
Fam83h
W/W), which showed autosomal recessive inheritance of these phenotypes. The KO of
FAM83H had controversial effects on the development of teeth and the formation of enamel. The phenotype defect in dental development and the enamel formation were seen in three mice among four generations. It can be concluded that null
FAM83H in outbred mice not only showed the reported phenotypes in null inbred mouse but also showed normal lifespan and reproductive ability; dental deficiency in three homozygous mice; and the symptoms that were similar to the symptoms of dry eye syndrome and curly coat dog syndrome in all four evaluated KO generations.
Protective effect of Abutilon indicum against lead‐induced reproductive toxicity in male Wistar rats
Authors: R. Santhoshkumar , S. Asha Devi 
Published: February 2019

AbstractDespite ample literature on the toxic impact of lead on the environment and health, the exact mechanism of pathogenesis/toxicity is not clearly known. Because it is well established that lead induces oxidative stress, it is assumed that exposure to antioxidants may reduce the toxic impact of lead. In this study, we evaluated the impact of coadministration of the methanolic root extract of a plant Abutilon indicum (50, 100, 200 mg kg
−1b.wt.) in mitigating the toxic impact of lead on the reproductive system of rats. In brief, Wistar rats were exposed to lead acetate in drinking water with or without coadministration of plant root extract and compared with that of control animals. After 45 days of exposure as outlined above, the animals were killed and the reproductive toxicity was assessed by sperm parameters, hormone and antioxidant enzyme assays, and testis histopathology. Significant reduction in testis weight, sperm count, testosterone levels, and antioxidant enzymes levels such as Superoxide Dismutase, Catalase, and Glutathione peroxidase was seen in lead‐treated animals, confirming the toxic impact. The coadministration of A. Indicum (100 and 200 mg kg
−1b.wt.) was found to bring the studied parameters close to the levels seen in untreated (control) animals. Our findings are indicative of the protective nature of A. Indicum against lead‐induced reproductive toxicity in a dose‐dependent manner. However, further characterization of the root extract is required to elucidate the probable mechanism of protection.
Paeonol reverses promoting effect of the HOTAIR/miR‐124/Notch1 axis on renal interstitial fibrosis in a rat model
Authors: Zhou Hao , Qiu Zhen‐Zhen , Yu Zuo‐Hua , Gao Lin , He Ji‐Ming , Zhang Zhi‐Wei , Zheng Jian 
Published: February 2019

AbstractRenal interstitial fibrosis (RIF) is a common manifestation of inflammatory and noninflammatory renal diseases, which correlates to renal excretory dysfunction. Recently, the long noncoding RNAs (lncRNAs) have been demonstrated to be involved in the development of various renal diseases. Here, we aim to determine whether paeonol (PAE) affects RIF with involvement of the lncRNA HOX transcript antisense intergenic RNA (HOTAIR)/microRNA‐124 (miR‐124)/Notch1 axis. RIF rat models were established by performing unilateral ureteral occlusion (UUO), in which interactions between HOTAIR, Notch1, and miR‐124 were determined. To identify the roles of PAE and HOTAIR in RIF, rats were injected with HOTAIR or PAE. Subsequently, to further investigate the underlying mechanism of PAE in RIF, epithelial to mesenchymal transition (EMT)‐ and migration‐related genes in NRK‐49F cells were measured. Next, rats were further treated with IMR‐1 (inhibitor of the Notch1/Jagged1 signaling pathway) to determine how PAE influences the Notch1/Jagged1 signaling pathway. HOTAIR interacted with miR‐124, and miR‐124 directly targeted Notch1, and HOTAIR was observed to be upregulated in RIF rats. PAE was found to decrease HOTAIR and Notch1 expression but to increase the miR‐124 expression in RIF rats. PAE inhibited EMT and migration of NRK‐49F cells facilitated by HOTAIR. HOTAIR activated the Notch1/Jagged1 signaling pathway by downregulating miR‐124, while PAE reversed these effects of HOTAIR on the Notch1/Jagged1 signaling pathway. Overall, our study demonstrates the contributory effect of lncRNA HOTAIR on RIF by activating the Notch1/Jagged1 signaling pathway via inhibition of miR‐124, whereas administration of PAE can alleviate the effects of HOTAIR on RIF.
Enhancement of tenogenic differentiation of rat tendon‐derived stem cells by biglycan
Authors: Zhang Yan‐Jing , Qing Quan , Zhang Ya‐Jing , Ning Liang‐Ju , Cui Jing , Yao Xuan , Luo Jing‐Cong , Ding Wei , Qin Ting‐Wu 
Published: February 2019

AbstractBiglycan (BGN) has been identified as one of the critical components of the tendon‐derived stem cells (TDSCs) niche and may be related to tendon formation. However, so far, no study has demonstrated whether the soluble BGN could induce the tenogenic differentiation of TDSCs in vitro. The aim of this study was to investigate the effect of BGN on the tenogenic differentiation of TDSCs. The proliferation and tenogenic differentiation of TDSCs exposed to different concentrations of BGN (0, 50, 100, and 500 ng/ml) were determined by the live/dead cell staining assay, CCK‐8 assay, quantitative real‐time polymerase chain reaction (qRT‐PCR), and western blot analysis. The BGN signaling pathway of TDSCs (with and without 50 ng/ml of BGN) was determined by western blot analysis and qRT‐PCR analysis. At a concentration of 50 ng/ml, BGN increased the expression of the tenogenic markers THBS‐4 and TNMD at both the messenger RNA (mRNA) and protein levels. Meanwhile, 50 ng/ml of BGN inhibited the expression of the chondrogenic and osteogenic markers SOX9, ACN, and RUNX2 at both the mRNA and protein levels. Moreover, BGN (50 ng/ml) affected the expression of the components of the extracellular matrix of TDSCs. Additionally, BGN activated the Smad1/5/8 pathway as indicated by an increase in phosphorylation and demonstrated by inhibition experiments. Upregulation in the gene expression of BMP‐associated receptors (BMPRII, ActR‐IIa, and BMPR‐Ib) and Smad pathway components (Smad4 and 8) was observed. Taken together, BGN regulates tenogenic differentiation of TDSCs via BMP7/Smad1/5/8 pathway and this regulation may provide a basic insight into treating tendon injury.
Factor VIII and vWF deficiency in STT3A‐CDG
Authors: Chang Irene J. , Byers Heather M. , Ng Bobby G. , Merritt John Lawrence , Gilmore Reid , Shrimal Shiteshu , Wei Wei , Zhang Yuan , Blair Amanda B. , Freeze Hudson H. , Zhang Bin , Lam Christina 
Published: January 2019

AbstractSTT3A‐CDG (OMIM# 615596) is an autosomal recessive N‐linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern. All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A. We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures. VWF in our patient's plasma is present in a mildly hypoglycosylated form. FVIII antigen levels were too low to quantify in our patient. Functional studies with STT3A−/− HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels. We also show decreased glycosylation of STT3A‐specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion. Our results suggest that certain STT3A‐dependent N‐glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level. Our report expands both the genotype and phenotype of STT3A‐CDG; demonstrating, as in most types of CDG, that there are multiple disease‐causing variants in STT3A.
MRI in pregnancy: Indications and practical considerations
Authors: Mervak Benjamin M. , Altun Ersan , McGinty Katrina A. , Hyslop W. Brian , Semelka Richard C. , Burke Lauren M. 
Published: January 2019

There is a constantly evolving knowledgebase regarding the safety of MRI in pregnant patients, as well as the safety of gadolinium administration, given potential fetal risks. This review provides an overview of national and international recommendations for patient screening and safety by trimester, evaluates the most recent literature regarding administration of gadolinium in pregnant patients, and discusses technical requirements when imaging pregnant patients. A protocol for imaging pregnant patients is provided, and multiple common indications for MRI in pregnancy are discussed.Level of Evidence 5.Technical Efficacy Stage 5.J. Magn. Reson. Imaging 2019;49:621–631.
Analysis of aortic pressure fields from 4D flow MRI in healthy volunteers: Associations with age and left ventricular remodeling
Authors: Bouaou Kevin , Bargiotas Ioannis , Dietenbeck Thomas , Bollache Emilie , Soulat Gilles , Craiem Damian , Houriez‐Gombaud‐Saintonge Sophia , De Cesare Alain , Gencer Umit , Giron Alain , Redheuil Alban , Messas Emmanuel , Lucor Didier , Mousseaux Elie , Kachenoura Nadjia 
Published: February 2019

BackgroundAging‐related arterial stiffness is associated with substantial changes in global and local arterial pressures. The subsequent early return of reflected pressure waves leads to an elevated left ventricular (LV) afterload and ultimately to a deleterious concentric LV remodeling.PurposeTo compute aortic time‐resolved pressure fields of healthy subjects from 4D flow MRI and to define relevant pressure‐based markers while investigating their relationship with age, LV remodeling, as well as tonometric augmentation index (AIx) and pulse wave velocity (PWV).Study TypeRetrospective.PopulationForty‐seven healthy subjects (age: 49.5 ± 18 years, 24 women).Field Strength/Sequence3 T/4D flow MRI.AssessmentSpatiotemporal pressure fields were computed by integrating velocity‐derived pressure gradients using Navier–Stokes equations, while assuming zero pressure at the sino‐tubular junction. To quantify aortic pressure spatiotemporal variations, we defined the following markers: 1) volumetric aortic pressure propagation rates ΔP
E1/ΔV and ΔP
E2/ΔV, representing variations of early and late systolic relative pressure peaks along the aorta, respectively, according to the cumulated aortic volume; 2) ΔA
PE1‐PE2 defined in four aortic regions as the absolute difference between early and late systolic relative pressure peaks amplitude.Statistical TestsLinear regression, Wilcoxon rank sum test, Bland–Altman analysis, and intraclass correlation coefficients (ICC).ResultsSpatiotemporal variations of aortic pressure peaks were moderately to highly reproducible (ICC ≥0.50) and decreased significantly with age, in terms of absolute magnitude: ΔP
E1/ΔV (r = 0.70, P < 0.005), ΔP
E2/ΔV (r = –0.45, P < 0.005) and ΔA
PE1‐PE2 (|r| > 0.39, P < 0.005). ΔP
E1/ΔV was associated with LV remodeling (r = 0.53, P < 0.001) and ascending aorta ΔA
PE1‐PE2 was associated with AIx (r = –0.59, P < 0.001). Both associations were independent of age and systolic blood pressures. Only weak associations were found between pressure indices and PWV (r ≤ 0.40).Data Conclusion4D flow MRI relative aortic pressures were consistent with physiological knowledge as demonstrated by their significant volumetric and temporal variations with age and their independent association with LV remodeling and augmentation index.Level of Evidence 2Technical Efficacy Stage 3J. Magn. Reson. Imaging 2019;50:982–993.
Elevated diastolic wall shear stress in regurgitant semilunar valvular lesions
Authors: Rizk Judy , Latus Heiner , Shehu Nerejda , Mkrtchyan Naira , Zimmermann Judith , Martinoff Stefan , Ewert Peter , Hennemuth Anja , Stern Heiko , Meierhofer Christian 
Published: February 2019

BackgroundAlterations in wall shear stress (WSS) assessed using 4D flow MRI have been shown to play a role in various vascular pathologies, such as bicuspid aortic valve aortopathy. Most studies have focused on systolic WSS, whereas altered diastolic hemodynamics in regurgitant semilunar valvular lesions have not so far been well characterized.PurposeTo investigate diastolic WSS in aortic and pulmonary regurgitation.Study TypeRetrospective data analysis.PopulationThirty tetralogy of Fallot patients, 19 bicuspid aortic valve patients, 11 healthy volunteers.Field Strength/Sequence5 T, 3D time‐resolved phase‐contrast MRI with 3D velocity encoding.AssessmentEstimation of WSS and its axial and circumferential vector components along cardiac cycle timeframes in the proximal main pulmonary artery in pulmonary regurgitation (PR) and in the proximal ascending aorta in aortic regurgitation (AR) as well as in healthy volunteers.Statistical TestsWilcoxon matched pairs test was used for intra‐group comparisons and Mann–Whitney test for intergroup comparisons. Correlations were assessed using Spearman correlation.ResultsWSS along the entire cardiac cycle was higher in PR and AR in comparison with controls (mean WSS 0.381 ± 0.070 vs. 0.220 ± 0.018, P < 0.0001; 0.361 ± 0.099 vs. 0.212 ± 0.030, P < 0.0001; respectively). Peak diastolic WSS was significantly higher than the mean WSS in AR and PR (P < 0.0001–0.005). The severity of PR correlated with the peak diastolic axial WSS (Spearman's r
s = 0.454, P = 0.018), whereas the severity of AR correlated with both peak systolic and diastolic tangential WSS (Spearman's r
s = 0.458, P = 0.049; r
s = 0.539, P = 0.017, respectively).Data ConclusionElevated diastolic WSS is a component of the altered flow hemodynamics in AR and PR. This may give more insight into the pathophysiologic role of WSS in vascular remodeling in AR and PR.Level of Evidence: 4Technical Efficacy Stage: 1J. Magn. Reson. Imaging 2019;50:763–770.
Left atrial appendage closure device implantation guided with fluoroscopy only: Long‐term results
Authors: Yuniadi Yoga , Hanafy Dicky A. , Raharjo Sunu B. , Yugo Dony 
Published: February 2019

AbstractBackgroundLeft atrial appendage (LAA) closure device is an alternative to anticoagulants for stroke prevention in selected atrial fibrillation (AF) patients. The LAA device implantation is safe with short period of learning curve. The standard implantation technique warrants a transesophageal echocardiography (TEE) guided and general anesthesia. In region of Asia Pacific as well as Indonesia, both TEE and general anesthesia are not always available in district hospital. We studied the safety and efficacy of Amplatzer Cardiac Plug (ACP) implantation guided by fluoroscopy only and without general anesthesia.MethodsConsecutive nonvalvular AF patients with CHA2DS2VASc score of ≥2 and HASBLED score of ≥3 are participated. Patients requiring long‐life anticoagulant for any other indication are excluded. The choice of implanted first or second‐generation ACP is that with excess size of 2‐4 mm of measured landing zone diameter.ResultsTwenty‐five subjects were implanted ACP by means fluoroscopy only (Group A) and 28 subjects using standard technique group (Group B). The median AF duration was 36 months (6‐276 months) and majority of patients (49%) are having permanent AF. The mean CHA2DS2VASc score is 3.9 ± 1.63. Successful implantation of ACPs was 96% in both groups. Nonfatal pericardial effusion occurred in three patients. During 75 weeks of follow‐up period, there were no significant differences of stroke event and death between groups.ConclusionACP implantation guided with fluoroscopy only is feasible and safe.
In‐office treatment of nasal valve obstruction using a novel, bipolar radiofrequency device
Authors: Jacobowitz Ofer , Driver Mark , Ephrat Moshe 
Published: February 2019

ObjectivesTo assess the safety and effectiveness of in‐office bipolar radiofrequency treatment of nasal valve obstructionStudy DesignProspective, nonrandomized, multicenter case seriesMethodsAdult patients with a Nasal Obstruction Symptom Evaluation scale (NOSE) score ≥60 were selected. Patients were clinically diagnosed with dynamic or static internal nasal valve obstruction as primary or significant contributor to obstruction and were required to have a positive response to nasal mechanical dilators or lateralization maneuvers. Bilateral radio‐frequency treatment was applied intranasally using a novel device, under local anesthesia in a single session. Safety and tolerance were assessed by event reporting, inspection, and Visual Analogue Scale (VAS) for pain. Efficacy was determined using the NOSE score and patient‐reported satisfaction survey at 26 weeks.ResultsFifty patients were treated. No device or procedure‐related serious adverse events occurred. Soreness, edema, and crusting resolved by 1 month. The mean baseline NOSE score was 79.9 (SD 10.8, range 60–100), and all had severe or extreme obstruction. At 26 weeks, mean NOSE score was 69% lower at 24.7 (P < .0001) with 95% two‐sided confidence intervals 48.5 to 61.1 for decrease. The decrease in NOSE score did not differ significantly between patients who did or did not have prior nasal surgery. Patient satisfaction mean by survey was 8.2 of 10.ConclusionIn office treatment of internal nasal valve obstruction using a bipolar radiofrequency device is safe and well‐tolerated. Nasal obstruction, as assessed using the NOSE questionnaire at 26 weeks, was markedly improved with high patient satisfaction.Level of Evidence2b, prospective cohort
Balance and gait in the elderly: A contemporary review
Authors: Osoba Muyinat Y. , Rao Ashwini K. , Agrawal Sunil K. , Lalwani Anil K. 
Published: February 2019

BackgroundThe prevalence of balance and gait deficits increases with age and is associated with the increased incidence of falls seen in the elderly population; these falls are associated with significant morbidity and mortality.ObjectivesTo review changes in gait and balance associated with aging and the effect of visual perturbations on gait and balance in the elderly to provide a basis for future research.MethodsPubMed and Cochrane Library were searched for articles from 1980 to present pertaining to gait and balance in older adults (>60) and younger adults (<60). Search terms included balance, posture, gait, locomotion, gait variability, gait disorders, gait disturbance, elderly, aging, falls, vision, visual, vestibular, and virtual reality. The references section of queried articles was also used to find relevant studies. Studies were excluded if subjects had a diagnosed gait or balance disorder.ResultsElderly adults show age‐related decline in sensory systems and reduced ability to adapt to changes in their environment to maintain balance. Elderly adults are particularly dependent on vision to maintain postural stability. Distinct changes in spatiotemporal gait parameters are associated with aging, such as slower gait and increased gait variability, which are amplified with exposure to visual perturbations. Increased gait variability, specifically with mediolateral perturbations, poses a particular challenge for elderly adults and is linked to increased falls risk. Virtual reality training has shown promising effects on balance and gait.ConclusionElderly adults show age‐related decline in balance and gait with increased gait variability and an associated increased risk of falls.Level of Evidence5