bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-377-3p inhibits atherosclerosis-associated vascular smooth muscle cell proliferation and migration via targeting neuropilin2
Authors: Wang Haijun , Wei Zheng , Li Hulun , Guan Yinghui , Han Zhiyang , Wang Hengzhen , Liu Bing 
Published: May 2020

Abstract
Vascular smooth muscle cell (VSMC) proliferation and migration are vital to atherosclerosis (AS) development and plaque rupture. MicroRNA-377-3p (miR-377-3p) has been reported to inhibit AS in apolipoprotein E knockout (ApoE−/−) mice. Herein, the mechanism underlying the effect of miR-377-3p on alleviating AS is explored. In vivo experiments, ApoE−/− mice were fed with high-fat diet (HFD) to induce AS and treated with miR-377-3p agomir or negative control agomir (agomir-NC) on week 0, 2, 4, 6, 8, 10 after HFD feeding. MiR-377-3p was found to restore HFD-induced AS lesions and expressions of matrix metalloproteinase (MMP)-2, MMP-9, α-smooth muscle actin (α-actin) and calponin. In in vitro experiments, human VSMCs were tranfected with miR-377-3p agomir or agomir-NC, followed by treatment with oxidized low-density lipoprotein (ox-LDL). MiR-377-3p was observed to significantly inhibit ox-LDL-induced VSMC proliferation characterized by inhibited cell viability, expressions of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E and cell cycle transition from G1 to S phase accompanied with less 5-Ethynyl-2′-deoxyuridine (EdU)-positive cells. Furthermore, MiR-377-3p significantly inhibited ox-LDL-induced VSMC migration characterized by inhibited wound closure and decreased relative VSMC migration. Besides, neuropilin2 (NRP2) was verified as a target of miR-377-3p. MiR-377-3p was observed to inhibit NRP2 expressions in vivo and in vitro. Moreover, miR-377-3p significantly inhibited MMP-2 and MMP-9 expressions in human VSMCs. Additionally, miR-377-3p-induced inhibition of VSMC proliferation and migration could be attenuated by NRP2 overexpression. These results indicated that miR-377-3p inhibited VSMC proliferation and migration via targeting NRP2. The present study provides an underlying mechanism for miR-377-3p-based AS therapy.
Schwannoma of the Greater Superficial Petrosal Nerve: An Unusual Site for a Common Tumor
Authors: Uppar Alok Mohan , Rao Shilpa , Prasad Chandrajit , Arimappamagan Arivazhagan , Santosh Vani 
Published: May 2020

AbstractGreater superficial petrosal nerve (GSPN) schwannoma is a rare clinical entity. It forms a small subset of the larger group of facial nerve schwannomas. A thorough literature search yielded only 27 such cases reported to date in the English literature. We present one such rare case of GSPN schwannoma and discuss the clinical spectrum and management along with a review of the literature. We demonstrate the surgical steps in an operative video.
Delayed Transfer of the Extensor Carpi Radialis Brevis Branch of the Radial Nerve to the Anterior Interosseous Nerve for Restoration of Thumb and Index Finger Flexion: Case Report
Authors: Salomão Renan , de Oliveira Jairo Porfírio , Junger Carolina Fernandes , Soares Ricardo Luiz Cezar , de Lima Carlos Roberto , Acioly Marcus Andre 
Published: May 2020

AbstractHigh median nerve injuries (HMNIs) are rare lesions involving the upper extremities and affect the median nerve from its origin to the emergence of the anterior interosseous nerve (AIN). Proximal reconstruction has long been considered the gold standard in treating HMNI, but thumb and index flexion and pinch and grip weakness are consistently not recovered. We report the surgical results of a patient affected by an HMNI with partial spontaneous recovery after a gunshot wound. AIN function was successfully restored in a delayed fashion by transferring the radial nerve branch to the extensor carpi radialis brevis to the AIN.
Combined Surgical Resection and Laser Interstitial Thermal Therapy for Glioblastoma: Technical Note
Authors: Vega Rafael A. , Traylor Jeffrey I. , Patel Rajan , Muir Matthew , Bastos Dheigo C.A. , Prabhu Sujit S. 
Published: May 2020

Abstract
Background Glioblastoma multiforme (GBM) is an aggressive intracranial malignancy that confers a poor prognosis despite maximum surgical resection and chemoradiotherapy. Survival decreases further with deep-seated lesions. Laser interstitial thermal therapy (LITT) is an emerging minimally invasive technique for tumor ablation shown to reduce tumor burden effectively, particularly in deep-seated locations less amenable to gross total resection. We describe our initial technical experience of using the combination of LITT followed by surgical resection in patients with GBMs that exhibit both an easily accessible and deep-seated component.
Materials and Methods Patients with GBM who received concurrent LITT and surgical resection at our institution were identified. Patient demographic and clinical information was procured from the University of Texas MD Anderson Cancer Center electronic medical record along with preoperative, postoperative, and 1-month follow-up magnetic resonance imaging (MRI).
Results Four patients (n = 2 male, n = 2 female) with IDH-wild type GBM who received combined LITT and surgical resection were identified and analyzed retrospectively. All patients received chemoradiotherapy before presentation. All but one patient (75%) received resection before presentation. Median age was 54 years (range: 44–56 years). Median length of hospital stay was 6.5 days (range: 2–47 days). Median extent of combined ablation/resection was 90.4%. One of the four patients experienced complications in the perioperative or immediate follow-up periods. Local recurrence was observed in one patient during the follow-up period.
Conclusion Malignant gliomas in deep-seated locations or in close proximity to white matter structures are challenging to manage. LITT followed by surgical resection may provide an alternative for tumor debulking that minimizes potential morbidities and extent of residual tumor. Further studies comparing this approach with standard resection techniques are warranted.
Exploring the Benefit of an Integrated Ophthalmology Internship (PGY-1)—Perceived Preparedness and the Recommended Duration of Training
Authors: Hou Andrew , Goyal Nikhil , Darnley-Fisch Deborah , Edwards Paul , Goldman David 
Published: May 2020

Abstract
Objective The effective utilization of intern training for ophthalmology residency is undermined by its variability across postgraduate programs. As residency programs shift toward integrating the first postgraduate year (PGY-1) into the ophthalmology-training curriculum, there are no definitive guidelines to build upon.
Methods This is a retrospective cross-sectional study of new second postgraduate year (PGY-2) ophthalmology residents. Residents were surveyed in their first 2 months of ophthalmology training. Residents were asked to self-assess preparedness for ophthalmology based on their PGY-1 curriculum. A survey was composed and modified from the Accreditation Council for Graduate Medical Education's assessment of resident training. The Wilcoxon's rank-sum test was used to evaluate survey differences between the transitional year (TY) versus preliminary internal medicine (IM) year and compare survey responses between residents who were below versus above optimal cut points for weeks of ophthalmic training.
Results There were 72 PGY-2 residents who responded to blinded surveys collected from July to August of 2017 and 2018. Thirty-nine (54%) residents graduated from a TY, 28 (39%) from preliminary IM, 3 (4%) from preliminary surgery, and 2 (3%) from a categorical ophthalmology year. Both categorical ophthalmology and surgery year were excluded from training year comparison due to low sample size. Using weeks of ophthalmology training as the control variable, there were significant increases in preparedness for addressing the ophthalmic complaint (p = 0.003) with at least 8 weeks of clinical ophthalmology, ability to perform ophthalmic exam (p = 0.018) with at least 12 weeks, ophthalmology medical knowledge (p = 0.005) with at least 10 weeks, and proficiency with hospital electronic health record (p = 0.003) with at least 12 weeks.
Conclusion While our study did not find significant differences in perceived preparedness for ophthalmology residency based on the type of PGY-1 programs completed, there were statistically significant associations for specific ophthalmology tasks. These findings suggested a potential merit of integrating 12 weeks of clinical ophthalmology training as a benchmark for resident preparedness.
“An equal right to comment”
Authors: Hatzidaki Ourania 
Published: May 2020

AbstractThis paper analyses a snapshot of a conflictive Greek YouTube polylogue dealing with the issue of public online female nudity and the norms pertaining to both the act itself and its verbal critique. The said polylogue contains a markedly high proportion of lay (im)politeness/(in)appropriateness evaluations (Locher and Watts 2005). By quantifying and critically analyzing key lexical impoliteness (Culpeper 2011) and metapragmatic markers contained in the evaluations, I identify the ways in which the norms of online verbal behaviour are discursively negotiated amongst the polylogue participants, focusing especially on the arguments and justifications underlying the suggested norms. It is found that, firstly, the notions of (im)politeness/(in)appropriateness emerge as open to fierce, yet heavily argument-supported discursive dispute; secondly, sexualized slang functions both as an object of critique and as an extremely versatile rhetorical instrument serving metapragmatic argumentation; and, thirdly, online (im)politeness/(in)appropriateness is construed not as a superficial matter of netiquette, but as a deeply ethical and political-ideological controversy, especially regarding speech liberty and political correctness.
A usage-based approach to productive use of inflectional patterns and level of lemma sophistication in adult heritage speakers’ performance
Authors: Karayayla Tuğba 
Published: May 2020

AbstractAdopting a usage-based perspective, the present study assesses the mental lexicon of Turkish heritage speakers in the UK (HSs,n = 31) regarding the productive use of formulaic inflectional suffix templates and the level of sophistication of the lemmas produced in free speech. We additionally explore input-related predictors of this performance by comparing HS performance to that of a group of previous generation immigrant bilinguals (IBs,n = 61), who are representative input providers, and of a group of monolinguals (n = 44). The results show that overall, both the HSs and IBs diverge from the monolinguals in that they use nominal suffix sequences less productively and rely on less sophisticated nominal lemmas. Their verbal productivity performance, however, remains intact. We argue that altered input results in a performance which diverges from that of the monolinguals but converges on the immigrant variety. The individual variability is partly explained by the amount of L1 passive exposure, indicating that the HSs are not sensitive only to the changes in the input available to them but also to the amount of it. These findings provide new insights into the line of research that describes HSs as incomplete due to their L1-divergent skills in comparison to a monolingual baseline.
Can music inspire translators?
Authors: Naranjo Beatriz 
Published: May 2020

AbstractThis article examines the role of musically-triggered narrative engagement in translation performance. An experimental study was conducted to investigate the potential of music to induce narrative engagement (NE), based on findings that suggest the influence of NE-relevant dimensions such as visualization and emotional involvement in translation. Participants translated two literary texts with opposing emotional content (happy and sad) in two different sound conditions (with and without music). Three hypotheses were formulated predicting a beneficial effect of music for narrative engagement as well as positive correlations between narrative engagement and translation quality and creativity. Results suggest an increase of visualization in the music condition and a correlation between visualization levels and accuracy scores. Retrospective questionnaires indicate a positive appraisal of the experience of translating with music at both the cognitive and emotional level, although further investigations is needed to validate the scale and confirm its reliability.
Invited Commentary: Biomarkers for Mortality Among Individuals With a History of Out-of-Home Care—Implications for Study Design and Conceptualizations of Risk
Authors: Brown Hilary K 
Published: May 2020

Abstract
Out-of-home care in childhood and adolescence has been shown to be associated with elevated risk for all-cause mortality in adulthood, with adverse socioeconomic, psychosocial, and health-related trajectories hypothesized to mediate this relationship. In the research letter by Batty and Hamer (Am J Epidemiol. 2021;190(1):176–178), the authors used data from the 1970 British birth cohort (n = 8,581) to examine risk of biomarkers for mortality in adults with a history of out-of-home care. While markers of inflammation, glucose metabolism, and lipids were less favorable in the exposed versus unexposed, differences between groups were small and were completely attenuated after adjustment. This study raises important issues regarding the design and conceptualization of future studies on the long-term outcomes of out-of-home care recipients. Such studies require more detailed information on duration of care, type of care setting, and reasons for care, all of which could affect outcome risk. Because the duration of follow-up is long, and attrition likely, authors should consider use of novel analytical techniques to account for selection bias, such as inverse probability weighting. Finally, a “chain-of-risk” approach to understanding outcomes might be warranted, given that risk is likely explained by accumulation of and prolonged exposure to adverse socioeconomic, psychosocial, and health risks.
The Silent Spring of Human Rights in Investment Arbitration: Jurisprudence Constante through Case-Law Trajectory
Authors: Joshi Riddhi Dhananjay , Gurpur Shashikala 
Published: May 2020

Abstract
As a niché body of jurisprudence, International Investment Arbitration has paradoxically remained aloof from developments in other related spheres of law. Increasingly, however, Tribunals have been compelled to reflect on matters arising out of a human rights narrative. This article studies the perspectives of certain stakeholders in choosing to employ human rights to further social, economic or environmental interests in an investment arbitration. These stakeholders are: Claimant, Respondent, Third Party Interveners, Tribunal, and Enforcing Jurisdiction. Reliance is placed on awards spanning 28 years from 1989 to 2017 under the ICSID regime as well as in ad hoc arbitrations under the UNCITRAL Rules. An analysis of trends in case law sheds light on the nature of a jurisprudence constante developing in this regard. The article also explores limitations to, and recommendations for, the engagement of human rights within the realms of Investment Arbitration.
A Sensitive and Optimized HPLC-FLD Method for the Simultaneous Quantification of Hydroxychloroquine and Its Two Metabolites in Blood of Systemic Lupus Erythematosus Patients
Authors: Luo Xuemei , Peng Ying , Ge Weihong 
Published: May 2020

Abstract
Quantification of hydroxychloroquine (HCQ) and its two metabolites desethylchloroquine and desethylhydroxychloroquine in human blood can provide insight into the pharmacokinetic/pharmacodynamic characteristics of HCQ for the treatment of systemic lupus erythematosus (SLE), which is crucial for the optimization of the therapy. A simple, sensitive and optimized high performance liquid chromatography with fluorescence detection method has been developed and validated for the simultaneous determination of HCQ and its two metabolites in human blood. After addition of internal standard chloroquine, the blood sample was deproteinized with 2-fold acetonitrile and separated on an YMC-Triart C18 column (250 × 4.6 mm, 5 μm) with a mobile phase of 20 mM sodium phosphate buffer solution containing 0.25% triethylamine (pH 8.0)—acetonitrile (60:40, v/v). The analytes were detected by using fluorescence detection at an excitation and emission wavelength of 337 and 405 nm, respectively. The method was linear over the range of 3–3000 ng/mL for all three analytes and the chromatographic run time was 9 min. The values for intra- and inter-day precisions were ranged from 1.3 to 7.3. This method was successfully applied to quantify the concentrations of HCQ and its two metabolites in blood of 92 SLE patients.
Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Gα oxidation
Authors: Kolijn Detmar , Pabel Steffen , Tian Yanna , Lódi Mária , Herwig Melissa , Carrizzo Albino , Zhazykbayeva Saltanat , Kovács Árpád , Fülöp Gábor Á , Falcão-Pires Inês , Reusch Peter H , Linthout Sophie Van , Papp Zoltán , van Heerebeek Loek , Vecchione Carmine , Maier Lars S , Ciccarelli Michele , Tschöpe Carsten , Mügge Andreas , Bagi Zsolt , Sossalla Samuel , Hamdani Nazha 
Published: May 2020

Abstract

Aims
Sodium-glucose-cotransporter-2 inhibitors showed favourable cardiovascular outcomes, but the underlying mechanisms are still elusive. This study investigated the mechanisms of empagliflozin in human and murine heart failure with preserved ejection fraction (HFpEF).

Methods and results
The acute mechanisms of empagliflozin were investigated in human myocardium from patients with HFpEF and murine ZDF obese rats, which were treated in vivo. As shown with immunoblots and ELISA, empagliflozin significantly suppressed increased levels of ICAM-1, VCAM-1, TNF-α, and IL-6 in human and murine HFpEF myocardium and attenuated pathological oxidative parameters (H2O2, 3-nitrotyrosine, GSH, lipid peroxide) in both cardiomyocyte cytosol and mitochondria in addition to improved endothelial vasorelaxation. In HFpEF, we found higher oxidative stress-dependent activation of eNOS leading to PKGIα oxidation. Interestingly, immunofluorescence imaging and electron microscopy revealed that oxidized PKG1α in HFpEF appeared as dimers/polymers localized to the outer-membrane of the cardiomyocyte. Empagliflozin reduced oxidative stress/eNOS-dependent PKGIα oxidation and polymerization resulting in a higher fraction of PKGIα monomers, which translocated back to the cytosol. Consequently, diminished NO levels, sGC activity, cGMP concentration, and PKGIα activity in HFpEF increased upon empagliflozin leading to improved phosphorylation of myofilament proteins. In skinned HFpEF cardiomyocytes, empagliflozin improved cardiomyocyte stiffness in an anti-oxidative/PKGIα-dependent manner. Monovariate linear regression analysis confirmed the correlation of oxidative stress and PKGIα polymerization with increased cardiomyocyte stiffness and diastolic dysfunction of the HFpEF patients.

Conclusion
Empagliflozin reduces inflammatory and oxidative stress in HFpEF and thereby improves the NO–sGC–cGMP–cascade and PKGIα activity via reduced PKGIα oxidation and polymerization leading to less pathological cardiomyocyte stiffness.
Prognostic value of left ventricular remodelling index in idiopathic dilated cardiomyopathy
Authors: Xu Yuanwei , Lin Jiayi , Liang Yaodan , Wan Ke , Li Weihao , Wang Jie , Zhu Yanjie , Mui David , Wang Lili , Li Yuancheng , Cheng Wei , Sun Jiayu , Zhang Qing , Han Yuchi , Chen Yucheng 
Published: May 2020

Abstract

Aims
To evaluate the prognostic value of left ventricular (LV) remodelling index (RI) in idiopathic dilated cardiomyopathy (DCM) patients.

Methods and results
We prospectively enrolled 412 idiopathic DCM patients and 130 age- and sex-matched healthy volunteers who underwent cardiovascular magnetic resonance imaging between September 2013 and March 2018. RI was defined as the cubic root of the LV end-diastolic volume divided by the mean LV wall thickness on basal short-axis slice. The primary endpoint included all-cause mortality and heart transplantation. The secondary endpoint included the primary endpoint and heart failure (HF) readmission. During the median follow-up of 28.1 months (interquartile range: 19.3–43.0 months), 62 (15.0%) and 143 (34.7%) patients reached the primary and secondary endpoints, respectively. Stepwise multivariate Cox regression showed that RI [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.11–1.30, P &lt; 0.001], late gadolinium enhancement (LGE) presence and log (N-terminal pro-B-type natriuretic peptide) were independent predictors of the primary endpoint, while RI (HR 1.15, 95% CI 1.08–1.23, P &lt; 0.001) and extracellular volume were independent predictors of the secondary endpoint. The addition of RI to LV ejection fraction (EF) and LGE presence showed significantly improved global χ2 for predicting primary and secondary endpoints (both P &lt; 0.001). Furthermore, RI derived from echocardiography also showed independent prognostic value for primary and secondary endpoints with clinical risk factors.

Conclusions
RI is an independent predictor of all-cause mortality, heart transplantation, and HF readmission in DCM patients and provides incremental prognostic value to LVEF and LGE presence.
Balloon atrial septostomy and transition of subcutaneous to intravenous prostacyclin infusion for rescuing advanced right heart failure in idiopathic pulmonary arterial hypertension: a case report
Authors: Liang Kae-Woei , Wang Kuo-Yang 
Published: May 2020

Abstract

Background
Intravenous (IV) prostacyclin analogues infusion and balloon atrial septostomy (BAS) are two important treatment options for managing advanced right heart failure in patients with idiopathic pulmonary arterial hypertension (IPAH). References and protocols are rare for dose titrations and transitions between subcutaneous and IV prostacyclin in functional Class IV IPAH patients. Balloon atrial septostomy is rarely done in very few expert centres.

Case summary
A young female with IPAH who had received maximal medication including subcutaneous prostacyclin analogues injection was admitted due to advanced right heart failure. She received ascites drainage twice. Later, we directly switched the administration route of prostacyclin from subcutaneous to IV at a ratio of 1:1 instantly. Such rapid conversion led her into a state of profound hypotension and drowsy consciousness, which was resolved after escalating IV inotropics and reducing prostacyclin dosage. Five days later, she received BAS under the guidance of intracardiac echocardiography. Her urine output increased and dyspnoea improved gradually. Six months later, clinical worsening happened again with increase of ascites and dyspnoea. She underwent 2nd and 3rd session of graded BAS with relief of symptoms again. She received permanent transition to IV prostacyclin analogues infusions via a peripherally inserted central catheter after three sessions of BAS.

Discussion
Balloon atrial septostomy is effective in stabilizing the critical right heart failure in IPAH patients but should be intended as a bridge to lung transplant procedure. Transition from subcutaneous to IV prostacyclin is helpful but needs to be titrated in proper aliquots and time intervals to avoid abrupt haemodynamic changes.