bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repurposing the FDA-Approved Antiviral Drug Ribavirin as Targeted Therapy for Nasopharyngeal Carcinoma
Authors: Huq Sakibul , Casaos Joshua , Serra Riccardo , Peters Michael , Xia Yuanxuan , Ding Andy S. , Ehresman Jeff , Kedda Jayanidhi N. , Morales Manuel , Gorelick Noah L. , Zhao Tianna , Ishida Wataru , Perdomo-Pantoja Alexander , Cecia Arba , Ji Chenchen , Suk Ian , Sidransky David , Brait Mariana , Brem Henry , Skuli Nicolas , Tyler Betty 
Published: June 2020

Abstract
Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma with a proclivity for systemic dissemination, leading many patients to present with advanced stage disease and fail available treatments. There is a notable lack of targeted therapies for NPC, despite working knowledge of multiple proteins with integral roles in NPC cancer biology. These proteins include EZH2, Snail, eIF4E, and IMPDH, which are all overexpressed in NPC and correlated with poor prognosis. These proteins are known to be modulated by ribavirin, an FDA-approved hepatitis C antiviral that has recently been repurposed as a promising therapeutic in several solid and hematologic malignancies. Here, we investigated the potential of ribavirin as a targeted anticancer agent in five human NPC cell lines. Using cellular growth assays, flow cytometry, BrdU cell proliferation assays, scratch wound assays, and invasion assays, we show in vitro that ribavirin decreases NPC cellular proliferation, migration, and invasion and promotes cell-cycle arrest and cell death. Modulation of EZH2, Snail, eIF4E, IMPDH, mTOR, and cyclin D1 were observed in Western blots and enzymatic activity assays in response to ribavirin treatment. As monotherapy, ribavirin reduced flank tumor growth in multiple NPC xenograft models in vivo. Most importantly, we demonstrate that ribavirin enhanced the effects of radiotherapy, a central component of NPC treatment, both in vitro and in vivo. Our work suggests that NPC responds to ribavirin-mediated EZH2, Snail, eIF4E, IMPDH, and mTOR changes and positions ribavirin for clinical evaluation as a potential addition to our NPC treatment armamentarium.
Munich Comparative Study
Authors: Georgiev Stanimir , Ewert Peter , Eicken Andreas , Hager Alfred , Hörer Jürgen , Cleuziou Julie , Meierhofer Christian , Tanase Daniel 
Published: June 2020

Background:
Percutaneous pulmonary valve implantation (PPVI) has become an important treatment of right ventricular outflow tract dysfunction. Studies directly comparing the long-term outcome of PPVI with the Melody valve to surgical pulmonary valve replacement (SPVR) are lacking.

Methods:
All patients treated with PPVI with the Melody valve and SPVR between January 2006 and December 2018 in our center were enrolled into a database and investigated with a standard follow-up protocol. The current study compares the outcomes in means of survival, reinterventions, infectious endocarditis, and performance of the valves.

Results:

The study included 452 patients, of whom 241 were treated with PPVI with the Melody valve and 211 patients with SPVR with different types of valves. Median follow-up time was 5.4 years (3 months to 12.5 years), and the total observation was 2449 patient-years. Estimated survival after 10 years was 94% in the Melody group and 92% in the SPVR group (
P
=0.47). There was no difference in the estimated survival free of surgery on the implanted valve at 10 years (Melody, 87%, versus SPVR, 87%;
P
=0.54) or in the survival with the originally implanted pulmonary valve (Melody group, 80%; SPVR group, 73%;
P
=0.46) between both groups. The annualized incidence of infective endocarditis was 1.6% in the Melody group and 0.5% in the SPVR group, and the estimated survival free of endocarditis did not differ significantly between groups (Melody group, 82%; SPVR group, 86%;
P
=0.082). Survival free of valve replacement because of infective endocarditis was comparable between both groups (Melody, 88%; SPVR, 88%;
P
=0.35).

Conclusions:
PPVI with the Melody valve and SPVR provides similar survival, freedom of reinterventions, and infective endocarditis with or without the need of replacement of the pulmonary valve. Being less invasive, PPVI should be considered a method for treatment for patients with dysfunctional right ventricular outflow tracts.
Cardiovascular Health Score and Lifetime Risk of Cardiovascular Disease
Authors: Bundy Joshua D. , Ning Hongyan , Zhong Victor W. , Paluch Amanda E. , Lloyd-Jones Donald M. , Wilkins John T. , Allen Norrina B. 
Published: June 2020

Background:
Long-term risks of cardiovascular disease (CVD) according to levels of cardiovascular health (CVH) have not been characterized in a diverse, representative population.

Methods and Results:
We pooled individual-level data from 30 447 participants (mean [SD] age, 55.0 [13.9] years; 60.6% women; 31.8% black) from 7 US cohort studies. We defined CVH based on levels of 7 American Heart Association health metrics, scored as ideal (2 points), intermediate (1 point), or poor (0 points). The total CVH score was used to quantify overall CVH as high (12–14 points), moderate (9–11 points), or low (0–8 points). We used a modified Kaplan-Meier analysis, accounting for the competing risk of death, to estimate the lifetime risk of CVD (composite of incident myocardial infarction, stroke, heart failure, or CVD death) separately in white and black men and women free of CVD at index ages of <40, 40 to 59, and ≥60 years. High CVH was more prevalent among women compared with men, white compared with black participants, and in younger compared with older participants. During 538 477 person-years of follow-up, we observed 6546 CVD events. In women aged 40 to 59 years, those with high CVH had lower lifetime risk (95% CI) of CVD (white women, 12.6% [2.6%–22.6%]; black women, 0.0%) compared with moderate (white women, 16.6% [13.0%–20.2%]; black women, 12.7% [6.8%–18.5%]) and low (white women, 33.8% [30.6%–37.1%]; black women, 34.7% [30.4%–39.0%]) CVH strata. Patterns were similar for men and individuals <40 and ≥60 years of age.

Conclusions:
Higher baseline CVH at all ages in adulthood is associated with substantially lower lifetime risk for CVD compared with moderate and low CVH, in white and black men and women in the United States. Public health and healthcare efforts aimed at maintaining and restoring higher CVH throughout the life course could provide substantial benefits for the population burden of CVD.
gp130 Controls Cardiomyocyte Proliferation and Heart Regeneration
Authors: Li Yandong , Feng Jie , Song Shen , Li Haotong , Yang Huijun , Zhou Bin , Li Yan , Yue Zhang , Lian Hong , Liu Lihui , Hu Shengshou , Nie Yu 
Published: June 2020

Background:
A key cause of the high mortality of cardiovascular diseases is the cardiomyocyte inability to renew after cardiac injury. As a promising strategy to supplement functional myocytes for cardiac repair, there is a pressing need to understand the cellular and molecular mechanisms of heart regeneration.

Methods:
Seven genetic mouse lines were used: global OSM (oncostatin M) knockout, monocyte-/macrophage-specific OSM deletion, cardiomyocyte-specific lines, including OSM receptor deletion, gp130 (glycoprotein 130) deletion, gp130 activation, and Yap (yes-associated protein) ablation with gp130 activation mice. A series of molecular signaling experiments, including RNA sequencing, immunostaining, coimmunoprecipitation, and imaging flow cytometry, were conducted. Two models of cardiac injury, apical resection and myocardial infarction operation, were performed in neonatal, juvenile, and adult mice. Heart regeneration and cardiac function were evaluated by Masson staining and echocardiography, respectively. Gene recombinant adenovirus-associated virus was constructed and infected myocardial-infarcted mice as a gene therapy.

Results:

OSM was identified by RNA sequencing as a key upstream regulator of cardiomyocyte proliferation during neonatal heart regeneration in mice. Cardiomyocyte proliferation and heart regeneration were suspended in neonatal mice after cardiac injury when OSM was conditionally knockout in macrophages. The cardiomyocyte-specific deficiency of the OSM receptor heterodimers, OSM receptor and gp130, individually in cardiomyocytes reduced myocyte proliferation and neonatal heart regeneration. Conditional activation of gp130 in cardiomyocytes promoted cardiomyocyte proliferation and heart regeneration in juvenile and adult mice. Using RNA sequencing and functional screening, we found that Src mediated gp130-triggered cardiomyocyte proliferation by activating Yap (yes-associated protein) with Y357 phosphorylation independently of the Hippo pathway. Cardiomyocyte-specific deletion of Yap in
Myh6-gp130

ACT

mice blocked the effect of gp130 activation–induced heart regeneration in juvenile mice. Gene therapy with adenovirus-associated virus encoding constitutively activated gp130 promoted cardiomyocyte proliferation and heart regeneration in adult mice after myocardial infarction.

Conclusions:
Macrophage recruitment is essential for heart regeneration through the secretion of OSM, which promotes cardiomyocyte proliferation. As the coreceptor of OSM, gp130 activation is sufficient to promote cardiomyocyte proliferation by activating Yap through Src during heart regeneration. gp130 is a potential therapeutic target to improve heart regeneration after cardiac injury.
The New Critical Edition of the Martyrdom of the Fifteen Martyrs of Tiberioupolis (BHG 1199) by Irini-Sophia Kiapidou and Several Problems of the Text
Authors: Lourié Basil 
Published: June 2020

Abstract
The review-article discusses the new critical edition of BHG 1199 and its traditional attribution to Theophylact of Ohrid (which is rejected). The legend representing the conversion of Bulgaria with no participation of Cyril and Methodius or their disciples must go back to the tenth century First Bulgarian kingdom.
Assessing the Educational Quality of Facebook Videos as an Informative Resource on Otitis Media
Authors: Kahn Chase I. , Wang Rita , Shetty Kunal , Huestis Mikayla J. , Cohen Michael B. , Levi Jessica R. 
Published: June 2020

ObjectiveThis study analyzes the quality and reliability of otitis media (OM) videos on Facebook and investigates whether the videos shared within the Facebook community are considered to be a valuable educational tool. The results of this study are important for providing clinicians with the necessary understanding about the video content that their patients may be exposed to.Study DesignCross‐sectional analysis of video content.SettingA new Facebook account was created to carry out a search for videos on OM.MethodsInclusion criteria were as follows: videos intended for educating patients or guardians on OM, videos in the English language, and videos with at least 1 share.ResultsA total of 364 videos were screened, and 62 fit our inclusion criteria for analysis. The majority (56%) of OM videos on Facebook focused on complementary and alternative medication without mentioning any current guidelines. A limited amount of videos (29%) made any mention to surgical treatment options for OM. There was a strong positive correlation (rho = 0.8419, P <. 001) between a video’s content and its reliability. There was no correlation seen between a video’s content and its shares (rho = −0.142, P =. 1359).ConclusionsThe majority of OM videos on Facebook are inadequate for educational value. Clinicians should know about the existence of videos on OM and the quality of information that parents are exposed to.
The effects of small-needle-knife therapy on pain and mobility from knee osteoarthritis: a pilot randomized-controlled study
Authors: Zhu Junchen , Zheng Zhiwen , Liu Yaomeng , Lawrie Sophie , Esser Patrick , Izadi Hooshang , Dawes Helen , Xia Zhidao , Wang Chao , Xiong Yingzong , Ma Xingfu , Wade Derick T 
Published: June 2020

Objective: To investigate the effect of small needle-knife therapy in people with painful knee osteoarthritis. Design: Pilot randomised, controlled trial. Setting: Rehabilitation hospital. Subjects: In-patients with osteo-arthritis of the knee. Interventions: Either 1 to 3 small needle-knife treatments over seven days or oral Celecoxib. All patients stayed in hospital three weeks, receiving the same mobility-focused rehabilitation. Measures: Oxford Knee Score (OKS), gait speed and kinematics were recorded at baseline, at three weeks (discharge) and at three-months (OKS only). Withdrawal from the study, and adverse events associated with the small needle knife therapy were recorded. Results: 83 patients were randomized: 44 into the control group, of whom 10 were lost by three weeks and 12 at 3 months; 39 into the experimental group of whom eight were lost at three weeks and three months. The mean (SE) OKS scores at baseline were Control 35.86 (1.05), Exp 38.38 (0.99); at three weeks 26.64 (0.97) and 21.94 (1.23); and at three months 25.83 (0.91) and 20.48 (1.14) The mean (SE) gait speed at baseline was 1.07 (0.03) m/sec (Control) and 0.98 (0.03), and at three weeks was 1.14 (0.03) and 1.12 (0.03) ( P < 0.05). Linear mixed model statistical analysis showed that the improvements in the experimental group were statistically significant for total OKS score at discharge and three months Conclusions: Small needle-knife therapy added to standard therapy for patients with knee osteoarthritis, was acceptable, safe and reduced pain and improved global function on the Oxford Knee Score. Further research is warranted.
A practical method of using the anatomical space of the vesicouterine ligament for laparoscopic radical hysterectomy: a retrospective cohort study
Authors: Wang Jing , Sun Lulu , Ni Ting , Huang Yong , Wang Lihua , Yuan Jiangjing , Fan Qiong , Li Yuhong , Wang Yudong 
Published: June 2020

Objective To investigate the practicality of a new method using anatomical spaces for performing standard laparoscopic radical hysterectomy (LRH) without ureteral injury in patients with cervical cancer. Methods Clinicopathological characteristics and perioperative complications were retrospectively analysed in 440 patients with stages IB1 to IIB cervical cancer. The patients were assigned to two of the following groups: LRH by our method of using anatomical landmarks (anatomical space group, n = 217) and the traditional method (traditional group, n = 223). Results The mean operative duration and time of vesicouterine ligament (VUL) dissection were significantly shorter (173.87 ± 30.39 vs. 210.83 ± 44.55 minutes; 32.75 ± 7.23 vs. 43.48 ± 11.22 minutes), and blood loss was less in the anatomical space group compared with the traditional group. The rate of the intraoperative complication of ureteral injury was also significantly lower in the anatomical space group compared with the traditional group (0 vs. 5). Conclusions LRH by the anatomical method, using the axillary space and other potential spaces as anatomical landmarks, results in less blood loss and reduced ureteral injury compared with the traditional method. This method is safe and practical for separating the ureter from the VUL in patients with cervical cancer.
Complete radiological response to first-line regorafenib in a patient with abdominal relapse of BRAF V600E mutated GIST
Authors: Nannini Margherita , Valerio Di Scioscio , Gruppioni Elisa , Altimari Annalisa , Chiusole Benedetta , Saponara Maristella , Pantaleo Maria Abbondanza , Brunello Antonella 
Published: June 2020

Up to 13% of KIT and PDGFRA wild-type (WT) gastrointestinal stromal tumours (GIST) harbour a BRAF mutation, mostly involving the exon 15 V600E hot spot. Even if BRAF mutation is recognized as druggable target in other solid tumours, currently advanced BRAF-mutant GIST share the same therapeutical algorithm of KIT/PDGFRA mutants. We report a complete radiological response in a 51-year-old woman with V600E BRAF-mutated metastatic GIST who was treated with regorafenib (REG) as first-line therapy. REG represents the standard third-line therapy for advanced GIST patients progressing on or failing to respond to imatinib and sunitinib. However, according to its wide spectrum of action, with MAPK signalling pathway blockade at different levels, metastatic KIT/PDGFRA WT, including BRAF mutants, may benefit from REG upfront in first line.
A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men
Authors: Swerdloff Ronald S. , Dudley Robert E. 
Published: June 2020

Background: A novel formulation of oral testosterone undecanoate (TU) was studied in a long- and short-term phase III trial to evaluate safety and efficacy. Methods: Hypogonadal men (age 18–65 years; two morning serum testosterone (T) <300 ng/dl with signs/symptoms) were recruited into a 365 day (trial I) or 105 day (trial II), randomized, multicenter trial. Patients were randomized 1:1 to oral TU ( n = 161) or T-gel ( n = 160) in trial I, and 3:1 to oral TU, twice daily (BID) JATENZO® ( n = 166) or a topical T product [Axiron® ( n = 56)] in trial II. Dose adjustments were based on average T concentrations ( Cavg). Efficacy was assessed based on T levels, body composition and bone density. Safety was assessed by standard clinical measures. Results: Oral TU efficacy (% of patients with eugonadal T Cavg) was 84% (serum Cavg = 628 ± 343 ng/dl) and 87% (serum T equivalent Cavg ≈ 489 ± 155 ng/dl) in trials I and II, respectively. Oral TU significantly ( p <0.0001) improved all Psychosexual Daily Questionnaire parameters in trials I and II. In trial I, lean mass increased 3.2 ± 2.7 kg and fat decreased by 2.4 ± 3.6 kg (both p <0.0001) and bone density improved in hip (+0.012 ± 0.0225 g/cm2) and spine (+0.018 ± 0.0422 g/cm2) after 365 days (both p <0.0001). Oral TU-associated adverse effects were consistent with other T-replacement therapies but oral TU patients experienced a greater number of mild gastrointestinal adverse effects. Oral TU subjects in both studies exhibited an increase in mean systolic blood pressure of about 3–5 mmHg. Oral TU was not associated with liver toxicity nor did it cause an elevation in high-sensitivity C-reactive protein or lipoprotein-associated phospholipase A2 (cardiovascular safety biomarkers) after 365 days of therapy. Conclusion: A new oral TU formulation was safe and effective and represents a significant therapeutic advance for the treatment of appropriate hypogonadal men.
Acute Onset Asymmetric Sensorimotor Paraparesis: Not Always Spinal!
Authors: Gupta Dhananjay , R Pradeep , Mehta Anish , Javali Mahendra , Acharya Purshottam T. , Srinivasa Rangasetty 
Published: June 2020

Objective: To report an atypical case of acute onset sensorimotor paraparesis secondary to bilateral cerebral stroke. Background: Acute onset paraparesis or paraplegia is usually secondary to a spinal cord disease. Central or cerebral causes of paraparesis are rare and include parasagittal and bilateral precentral lesions. Design/Methods: Case report and literature review. Results: A 65-year-old man presented with acute onset weakness of both lower limbs, associated with pins and needle sensation. On examination, he was found to have paraparesis (grade 2/5, both legs) and an asymmetric sensory loss in both legs and thighs. Spinal magnetic resonance imaging ruled out any compressive or noncompressive etiology. Magnetic resonance imaging of the brain showed an acute infarction in the bilateral cerebral hemisphere in both the pre- and postcentral gyrus. An angiogram of the brain revealed an aplastic right ACA-A1 with left ACA-A1 feeding bilateral A2. There was distal left ACA-A1 stenosis seen, the probable cause of bilateral stroke in this patient. The patient was treated conservatively and showed symptomatic improvement during the course of stay at the hospital. Conclusion: This case of acute paraparesis secondary to bilateral cerebral infarction demonstrates the need to always look for a cerebral cause. In patients with cerebral infarction, who present early to a hospital, it may provide a window for thrombolytic or endovascular therapy.
Transplanted stents: a case report
Authors: Kainz Frieda-Maria , Wallner Stephanie , Uyanik-Uenal Keziban , Andreas Martin , Zuckermann Andreas 
Published: June 2020

Abstract
Background
An optimal donor work-up to exclude preexisting conditions is recommended, but urgency and technical equipment in donor centers must be considered. We report a case of two coronary stents present in the donor heart and the related long-term outcome.

Case presentation
A 59-year-old European male patient suffering from dilated cardiomyopathy with severely reduced left ventricular function and presenting with NYHA III underwent cardiac transplantation in 2004. At the one-year follow-up, during routine cardiac catheterization, two stents were found, one in the right coronary artery and one in the circumflex artery, in the patient’s transplanted heart. As no stent implantation was performed since transplantation, these were present prior to transplantation and had been transplanted without causing clinical signs. One of the stents showed in-stent restenosis, and the patient received an additional stent 7 years after transplantation. The other stent still showed a good result, and no further intervention has been required so far. The patient is currently in good clinical condition.

Conclusion
This is the first case report of favorable long-term stented coronary arteries prior to transplantation. This case highlights the importance of the donor work-up and meticulous palpation of the coronary arteries during donor evaluation.
Congenital heart disease diagnosed with echocardiogram in newborns with asymptomatic cardiac murmurs: a systematic review
Authors: Yoon Shin Ae , Hong Woi Hyun , Cho Hwa Jin 
Published: June 2020

Abstract
Background
More than 50% of newborns with congenital heart disease (CHD) are unrecognized at birth; however, the use of echocardiogram (Echo) for diagnosing CHD in newborns with asymptomatic, non-syndromic cardiac murmurs (ANCM), has not been systematically reviewed yet. We aimed to identify the incidence of CHD diagnosed with Echo and systematically review whether Echo should be recommended in this patient group.

Methods
The methodology utilized in this systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. Using the MEDLINE, EMBASE, Web of Science, and Cochrane Library databases, we performed a systematic review of publications reporting CHD diagnosed with Echo in newborns with cardiac murmurs. The quality of the included studies was evaluated using the Study Quality Assessment Tools developed by the National Institutes of Health.

Results
Of the 630 studies screened, six cohort studies, four cross-sectional studies, and two case reports were included in this review. The incidence of cardiac murmurs ranged from 0.6–8.6%. Among the 1928 newborns with ANCM, 719 (37.3%) were diagnosed with Echo as having CHD, and ventricular septal defect was the most common congenital malformation. More than 50% of the newborns showed moderate CHD necessitating outpatient cardiology follow-up, and 2.5% had severe CHD requiring immediate interventions, such as cardiac catheterization and heart surgery.

Conclusions
In this systematic review, a high incidence of CHD in newborns with ANCM was detected using Echo. This indicates that the use of Echo for diagnosing CHD in healthy newborns with cardiac murmurs could be helpful in earlier detection of CHD, thereby improving clinical outcomes for newborns with severe CHD.