bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunobiology of Merkel cell carcinoma
Authors: Samimi Mahtab , Kervarrec Thibault , Touze Antoine 
Published: January 2020

Purpose of review
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer, which is associated in 80% of cases with the Merkel cell polyomavirus (MCPyV). Advanced stages respond to immune checkpoint inhibitors in 50% of cases. Major issues remain unanswered regarding its oncogenesis and optimal treatment.

Recent findings
MCPyV-negative and MCPyV-positive MCCs have been hypothesized to derive from distinct cells, although the cell of origin remains a matter of debate. The crucial role the MCPyV small T oncoprotein was recently confirmed by its ability to inactivate p53, together with its contribution to the metastatic progression. In advanced cases, tumoral microenvironment may adequately predict responses to immunotherapies, and several mechanisms of primary and secondary resistance have been investigated.

Summary
Identifying the mechanisms of oncogenesis allow experimentation of new therapeutic targets, which remain mandatory even at the era of immunotherapies. Although new insights in the mechanisms of primary and secondary resistance pave the way for development of further immunotherapy strategies, neoadjuvant strategies may challenge our whole approach of the disease.
Research progress on the etiology and pathogenesis of adolescent idiopathic scoliosis
Authors: Peng Yue , Wang Sheng-Ru , Qiu Gui-Xing , Zhang Jian-Guo , Zhuang Qian-Yu 
Published: January 2020

AbstractEtiology of adolescent idiopathic scoliosis (AIS), a complicated three-dimensional spinal deformity with early-onset, receives continuous attention but remains unclear. To gain an insight into AIS pathogenesis, this review searched PubMed database up to June 2019, using key words or medical subject headings terms including “adolescent idiopathic scoliosis,” “scoliosis,” “pathogenesis,” “etiology,” “genetics,” “mesenchymal stem cells,” and their combinations, summarized existing literatures and categorized the theories or hypothesis into nine aspects. These aspects include bone marrow mesenchymal stem cell studies, genetic studies, tissue analysis, spine biomechanics measurements, neurologic analysis, hormone studies, biochemical analysis, environmental factor analysis, and lifestyle explorations. These categories could be a guidance for further etiology or treatment researches to gain inspiration.
Systemic Management for Nonmetastatic Castration-resistant Prostate Cancer
Authors: Liu Zefu , Zhang Tong , Ma Zikun , Zheng Shiyang , Chen Junying , Wu Zhiming , Zheng Xia , Li Xiangdong , Liu Zhuowei 
Published: January 2020

Purpose:
To indirectly compare the efficacy and safety of systemic therapies used for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).

Methods:
The relevant randomized controlled trials were retrieved from PubMed and the Cochrane Library. Network meta-analyses were used to compare multiple drugs simultaneously for the outcomes of nmCRPC. Direct evidence in trials and indirect evidence across trials were combined by the network meta-analyses to estimate the treatment efficiency.

Outcome:
Eight studies were included in our research. For prostate-specific antigen progression-free survival, the rate of progression was significantly decreased following apalutamide, enzalutamide, bicalutamide+dutasteride, and bicalutamide treatment compared with placebo. Compared with placebo treatment, metastases-free survival was significantly increased in patients who received apalutamide (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.23-0.35), enzalutamide (HR: 0.29, 95% CI: 0.24-0.35), and darolutamide (HR: 0.42, 95% CI: 0.35-0.50). Direct comparison showed significant survival benefits in patients who received second-generation anti-androgen therapy (apalutamide, enzalutamide, and darolutamide: HR: 0.74, 95% CI: 0.61-0.91) compared with patients who received placebo. With respect to metastases-free survival, based on SUCRA analysis, there was 80% and 78% probability that apalutamide and enzalutamide were preferred treatment, while darolutamide was likely to be second-best choice. Compared with placebo, all agents were not associated with significantly higher likelihood of serious adverse events and grade 3 to 4 adverse events.

Conclusion:
Our outcomes support equivalent efficacy and similar risk of adverse effects between apalutamide, enzalutamide, and darolutamide, supporting the use of these antiandrogen agents in high-risk of progression nmCRPC.
Cardiac Monitoring for Thoracic Radiation Therapy
Authors: Amin Neha P. , Desai Nina , Kim Samuel M. , Agarwal Manuj , Amin Nivee P. 
Published: January 2020

Objective:
The American Society of Clinical Oncology (ASCO) 2017 guidelines on cardiac monitoring during cancer treatments identified patients receiving thoracic radiation (TRT) ≥30 Gy (heart in field) at increased risk for developing radiation-induced heart disease (RIHD). ASCO encouraged clinicians to actively screen and monitor for baseline modifiable cardiac risk factors and therapy-induced cardiotoxicity in this high-risk population. Coronary artery calcium (CAC) is an independent risk factor for adverse cardiac events that can be mitigated with preventative medical therapy. It is unclear whether radiation oncologists (ROs) are aware of ASCO guidelines or the implications of CAC observed on computed tomographic scans. We report on practice patterns, perceptions, and experiences of cardiac monitoring for patients receiving definitive TRT, excluding breast patients.

Materials and Methods:
A 28-question survey was emailed to United States ROs 3 times from September 2018 to January 2019.

Results:
There were 162 respondents from 42 states, 51% in academic practice. Most ROs (81%) were not aware of the ASCO guidelines. Only 24% agreed with the guidelines, only 27% believed symptomatic RIHD could manifest within 2 years of TRT, and 69% thought there was a lack of strong evidence for type and timing of cardiac monitoring tests. If CAC was evident on computed tomographic scans, 40% took no further action to inform the patient or referring doctor.

Conclusions:
This survey highlights a critical gap in knowledge about cardiac monitoring and potentially life-saving opportunities for preventive cardiac medical management. Future studies focusing on timing and detection of RIHD may elucidate the utility of cardiac monitoring for TRT patients.
Systemic and regional cerebral perfusion in small infants undergoing minor lower abdominal surgery under awake caudal anaesthesia
Authors: Beck Christiane E. , Sümpelmann Robert , Nickel Katja , Keil Oliver , Kuebler Jochen F. , Boethig Dietmar , Witt Lars , Dennhardt Nils 
Published: January 2020

BACKGROUND
Infants undergoing general anaesthesia have an increased risk of severe respiratory and cardiovascular critical events. Awake caudal anaesthesia is an alternative for small infants undergoing minor lower abdominal surgery. While clinical experience has shown stable intra-operative haemodynamic conditions, there are no studies evaluating systemic and regional cerebral perfusion during such a procedure.

OBJECTIVES
The purpose of this study was to evaluate the effects of awake caudal anaesthesia on systemic and regional cerebral perfusion in small infants.

DESIGN
A prospective observational cohort study.

SETTING
Clinic of Anaesthesiology, University Children's Hospital, between November 2017 and June 2018.

PATIENTS
Twenty small infants (postmenstrual age 36 to 54 weeks, weight 1800 to 5700 g) scheduled for lower abdominal surgery under awake caudal anaesthesia were enrolled in this study.

INTERVENTION
Standard monitoring was expanded to include cardiac index using electrical velocimetry and regional cerebral oxygen saturation using near infrared spectroscopy. The caudal block was performed with 0.3% ropivacaine 1 ml kg−1 Hypotension was defined as mean arterial blood pressure (BP) less than 35 mmHg and regional cerebral desaturation as regional cerebral oxygen saturation less than 80% of baseline.

MAIN OUTCOMES
Mean arterial BP, cardiac index and regional cerebral oxygen saturation parameters under awake caudal anaesthesia.

RESULTS
Mean arterial BP, cardiac index and regional cerebral oxygen saturation remained above the predefined lower limits. No episodes of hypotension or regional cerebral desaturation were observed. Operation time was 35 ± 13 (range 20 to 71) min. The infants were discharged to the neonatal ward after the end of surgery, and milk was fed 22 ± 15 (range 6 to 55) min thereafter. Five preterm infants experienced self-limiting episodes of apnoea intra-operatively.

CONCLUSION
The current study shows that awake caudal anaesthesia does not impair systemic and regional cerebral perfusion in small infants.

TRIAL REGISTRATION
German registry of clinical studies (DRKS-ID: 800015742).
Goal-directed therapy with bolus albumin 5% is not superior to bolus ringer acetate in maintaining systemic and mesenteric oxygen delivery in major upper abdominal surgery
Authors: Bisgaard Jannie , Madsen Rasmus , Dybdal Lene L. , Lauridsen Jørgen T. , Mortensen Michael B. , Jensen Anders G. 
Published: January 2020

BACKGROUND
Goal-directed therapy (GDT) is increasingly used in abdominal surgery. Whether crystalloids can exert the same effect as colloid, and how this may affect perfusion, is still unclear. The effect of GDT on the systemic oxygen delivery index (sDO2I) and the mesenteric oxygen delivery index (mDO2I) can be quantified by measuring cardiac index and flow in the superior mesenteric artery, respectively.

OBJECTIVE
The aim of this study was to test the hypothesis that intra-operative GDT with bolus human albumin 5% is superior to GDT with bolus ringer acetate in maintaining sDO2I and mDO2I in elective major upper gastrointestinal cancer surgery.

DESIGN
Randomised controlled double blinded trial.

SETTING
Odense University Hospital, Denmark, from May 2014 to June 2015.

PATIENTS
A total of 89 adults scheduled for elective major upper gastrointestinal cancer surgery were randomised and data from 60 were analysed. Exclusion criteria: contraindications for using the LiDCOplus system, known allergy to albumin, pre-operative renal failure, pancreatic cancer and pre-operative down staging using chemotherapy and/or radiation therapy, pregnancy.

INTERVENTIONS
Patients were randomised to intra-operative GDT with either bolus human albumin or ringer acetate 250 ml, guided by pulse pressure variation and stroke volume.

MAIN OUTCOME MEASURES
Changes in sDO2I and mDO2I. Secondary outcomes were changes in other haemodynamic variables, fluid balance, blood transfusions, fluid-related complications and length of stay (LOS) in ICU and hospital.

RESULTS
Median [IQR] sDO2I was 522 [420 to 665] ml min−1 m−2 in the ringer acetate group and 490 [363 to 676] ml min−1 m−2 in the human albumin group, P = 0.36. Median [IQR] mDO2I was 12.1 [5.8 to 28.7] ml min−1 m−2 in the ringer acetate group and 17.0 [7.6 to 27.5] ml min−1 m−2 in the human albumin group, P = 0.17. Other haemodynamic comparisons did not differ significantly. More trial fluid was administered in the ringer acetate group. We found no significant difference in transfusions, complications or LOS.

CONCLUSION
Bolus human albumin 5% was not superior to bolus ringer acetate in maintaining systemic or mesenteric oxygen delivery in elective major upper gastrointestinal cancer surgery, despite the administration of larger volumes of trial fluid in the ringer acetate group. No significant difference was seen in fluid-related complications or LOS.

TRIAL REGISTRATION

https://eudract.ema.europa.eu/ Identifier: 2013-002217-36.
Modes of bioprosthetic valve failure: a narrative review
Authors: Koziarz Alex , Makhdoum Ahmad , Butany Jagdish , Ouzounian Maral , Chung Jennifer 
Published: January 2020

Purpose of review
A thorough understanding of the modes of bioprosthetic valve failure is critical as clinicians will be facing an increasing number of patients presenting with failed bioprostheses in coming years. The purpose of this article is to review modes of bioprosthestic valve degeneration, their management, and identify gaps for future research.

Recent findings
Guidelines recommend monitoring hemodynamic performance of prosthetic valves using serial echocardiograms to determine valve function and presence of valve degeneration. Modes of bioprosthetic valve failure may be categorized as structural degeneration (calcification, tears, fibrosis, flail), nonstructural degeneration (pannus), thrombosis, and endocarditis. Calcification is the most common form of structural valve degeneration. Predictors of bioprosthetic valve failure include valves implanted in the mitral position, younger age, and type of valve (porcine versus bovine pericardial). Failed bioprosthetic valves are managed with either redo surgical replacement or transcatheter valve-in-valve implantation.

Summary
Several modes of bioprosthetic valve failure exist, which vary based on patient, implant position, and valve characteristics. Further research is required to characterize factors associated with early failure to delay structural valve degeneration and improve patient prognosis.
Blood pressure and the risk of major adverse cardiovascular events among firefighters
Authors: Noh Juhwan , Lee Chan Joo , Hyun Dae-Sung , Kim Woojin , Kim Mi-Ji , Park Ki-Soo , Koh Sangbaek , Chang Sei-Jin , Kim Changsoo , Park Sungha 
Published: January 2020

Objective:
No long-term follow-up study has investigated the effect of blood pressure (BP) on cardiovascular disease mortality and morbidity in firefighters. To investigate the effects of BP on the risk of major adverse cardiovascular events (MACEs) using a national representative population-matched cohort.

Methods:
We enrolled all firefighters (N = 8242) and 28 678 referent controls aged more than 40 years who underwent baseline health examinations in 2002 and 2003. Records of hospitalization and mortality until 2015 were checked. To evaluate the causal effect of BP on MACE, subcohort analysis using a propensity score-matched (PSM) cohort with respect to job classification (firefighter vs. control) was performed.

Results:
Hypertension significantly increased the risk of MACEs compared with normal BP in both firefighters and the age--sex matched cohort, but in participants with elevated BP, significantly increased risk of MACEs [hazards ratio 1.41, 95% confidence interval (CI) 1.06–1.88] was observed only among firefighters. In the PSM cohort, firefighters had a significantly higher risk of death or hospitalization from MACEs (hazard ratio 1.29, 95% CI 1.14–1.47), myocardial infarction (hazard ratio 1.24, 95% CI 1.07–1.43), and ischemic stroke (hazard ratio 1.43, 95% CI 1.12–1.82) than controls. Firefighters with elevated BP (hazard ratio 1.58, 95% CI 1.04–2.40), stage 1 (hazard ratio 1.24, 95% CI 1.00–1.52), and stage 2 (hazard ratio 1.39, 95% CI 1.13–1.71) hypertension had higher risk of MACEs than PSM controls.

Conclusion:
Firefighters showed significantly higher cardiovascular risk than referent controls when comparing those within the same BP category, suggesting that firefighters with elevated BP and hypertension may be at high risk of adverse prognosis.
MASSIVE RETINAL NEOVASCULARIZATION IN VON HIPPEL–LINDAU DISEASE: ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR, VITRECTOMY, IMMUNOHISTOCHEMISTRY, AND OPTICAL COHERENCE TOMOGRAPHY FEATURES
Authors: Kreuz André Carvalho , Zacharias Leandro Cabral , Oliveira Raíza Dantas de Lira , Ferreira Bruno Fortaleza de Aquino , de Lima Patrícia Picciarelli , Pimentel Sérgio Luís Gianotti 
Published: January 2020

Purpose:
To report a rare presentation of ocular von Hippel–Lindau disease associated with a massive epiretinal vascular proliferation over the macula removed by vitrectomy and submitted to histological analysis.

Methods:
Interventional case report.

Results:
A 13-year-old woman with von Hippel–Lindau disease reported progressive visual loss in the right eye over the preceding 6 months. Best-corrected visual acuity was 20/100 in the right eye. Fundoscopy showed retinal neovascularization (RNV) with macular traction and a small superotemporal hemangioblastoma. Spectral-domain optical coherence tomography confirmed increased macular thickness and macular traction secondary to RNV. Bevacizumab was injected intravitreally, resulting in partial regression of RNV. Five days after the injection, the patient underwent complete removal of fibrovascular proliferation via pars plana vitrectomy, followed by peripheral tumor photocoagulation. The specimen was subjected to histopathological and immunohistochemical analyses. At 2 years of follow-up, vision had improved to 20/30, and anatomical improvement was confirmed on both fundoscopy and spectral-domain optical coherence tomography.

Conclusion:
Ocular von Hippel–Lindau disease may be associated with RNV and macular traction. In such cases, RNV is likely responsive to anti–vascular endothelial growth factor and may be removed surgically along a cleavage plane between the tissue proliferation and the inner retina. In the reported case, the procedure was found to be safe and associated with macular anatomical improvement and vision recovery.
RETINAL TEARS DUE TO PICKLEBALL INJURY
Authors: Atkinson Catherine F. , Patron Mark E. , Joondeph Brian C. 
Published: January 2020

Purpose:
This is the first case series of two instances of retinal tears due to an injury sustained while playing pickleball.

Methods:
Case series.

Results:
A 66-year old white man presented with a symptomatic retinal tear, localized retinal detachment, and mild vitreous hemorrhage nine days after he was hit in his left eye while playing pickleball. The patient was not wearing eye protection while playing. The patient was treated with cryotherapy, and after three weeks, the vitreous hemorrhage and retinal detachment resolved. In addition, a 60-year-old woman presented with a posterior vitreous detachment and a symptomatic retinal tear 1 month after blunt trauma to her left eye from a pickleball injury. She underwent successful laser retinopexy treatment.

Conclusion:
Proper eye protection should be strongly considered while playing pickleball, especially in the elderly population or in individuals who are at higher risk for retinal detachment.
Human induced pluripotent stem cell-derived GABAergic interneuron transplants attenuate neuropathic pain
Authors: Manion John , Khuong Thang , Harney Dylan , Littleboy Jamie B. , Ruan Travis , Loo Lipin , Costigan Michael , Larance Mark , Caron Leslie , Neely G. Gregory 
Published: January 2020

Abstract
Neuropathic pain causes severe suffering, and most patients are resistant to current therapies. A core element of neuropathic pain is the loss of inhibitory tone in the spinal cord. Previous studies have shown that foetal GABAergic neuron precursors can provide relief from pain. However, the source of these precursor cells and their multipotent status make them unsuitable for therapeutic use. Here, we extend these findings by showing, for the first time, that spinally transplanted, terminally differentiated human induced pluripotent stem cell-derived GABAergic (iGABAergic) neurons provide significant, long-term, and safe relief from neuropathic pain induced by peripheral nerve injury in mice. Furthermore, iGABAergic neuron transplants survive long term in the injured spinal cord and show evidence of synaptic integration. Together, this provides the proof in principle for the first viable GABAergic transplants to treat human neuropathic pain patients.
Determinants of Workplace Bullying Types and Their Relationship With Depression Among Female Nurses
Authors: KO Ying-Ying , LIU Yi , WANG Chi-Jane , LIAO Hsiu-Yun , LIAO Yu-Mei , CHEN Hsing-Mei 
Published: January 2020

ABSTRACT

Background
Workplace bullying is commonly experienced by nurses worldwide.

Purpose
This study was conducted to examine the determinants of different types of workplace bullying and their relationship to depression in female nurses.

Methods
A cross-sectional correlational study was employed, and 484 female nurses from a large medical center in southern Taiwan completed the questionnaire. Data were analyzed using logistic regression analysis.

Results
Being unmarried and working in medical/surgical units were found to be the major determinants of work-related bullying, whereas being unmarried was found to be the single determinant of person-related and physical-intimidation bullying. Moreover, work-related and person-related bullying were both found to be significant determinants of depression.

Conclusions/Implications for Practice
Nursing administrators should establish workplace-bullying prevention and management strategies by setting reasonable and equal workloads for nurses, assigning tasks equitably, and building depression-related support and consultation groups.
The Smartphone Addiction Levels and the Association With Communication Skills in Nursing and Medical School Students
Authors: CELIKKALP Ulfiye , BILGIC Sebnem , TEMEL Munire , VAROL Gamze 
Published: January 2020

ABSTRACT

Background
The use of smartphones among young people is quite common. However, smartphones are associated with negative effects when used excessively. It has been reported that smartphone use may adversely affect learning in the classroom, cause safety issues, and negatively affect interpersonal communications.

Purpose
The aims of this study were to determine the level of smartphone addiction among nursing and medical school students and to examine the effect of smartphone addiction level on communication skills.

Methods
This cross-sectional study was conducted with medical school and nursing students at a public university (502 participants). Data were collected using a personal information form, the Smartphone Addiction Scale–Short Version (SAS-SV), and the Communication Skills Assessment Scale.

Results
All of the participants in the study owned smartphones. Most (70.9%) were female, and 58.2% were in the nursing program. The participants used smartphones for a mean time of 5.07 ± 3.32 hours a day, primarily for messaging. The mean total SAS-SV score for the participants was 31.89 ± 9.90, and a significant difference in SAS-SV mean scores was found with regard to the variables of department, gender, daily smartphone use duration, academic success, status regarding smartphone use in the classroom, participation in sports, easy communication with patients and relatives, preferred mode of communication, health problems tied to phone use, and injury status (p < .05). In addition, a positive weak-to-moderate relationship was found between SAS-SV mean scores and the variables of daily smartphone use duration and years of smartphone use, whereas a negative weak relationship was found between SAS-SV mean scores and Communication Skills Assessment Scale scores. Daily smartphone use duration was found to be the most important predictor of smartphone addiction.

Conclusions/Implications for Practice
Higher SAS-SV scores have a negative impact on interpersonal communication and social life and reduce learning efficacy in students. Therefore, students and lecturers should be better informed regarding the benefits and risks of smartphone use in education, with precautions provided against excessive and needless use.