bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Heart of Classical Work-Performance
Authors: Kania Andrew 
Published: April 2021

AbstractIn this critical study of Julian Dodd’s Being True to Works of Music (2020), I argue that the three-tier normative profile of the work-performance tradition in classical music that Dodd defends should be rejected in favour of a two-tier version. I also argue that the theory of work-performance defended in the book fits much more naturally with a contextualist ontology of musical works than with the Platonist ontology Dodd defends in Works of Music (2007), despite his arguments to the contrary in the afterword of the new book. Finally, I argue that the reasons he gives for preferring a ‘tradition-based’ over a ‘historicized’ theory of the understanding of classical scores are not convincing.
Cerebral Embolism as a Result of Facial Filler Injections: A Literature Review
Authors: Wang Hayson Chenyu , Yu Nanze , Wang Xiaojun , Dong Ruijia , Long Xiao , Feng Xin , Li Jianle , Wu Woffles T L 
Published: April 2021

Abstract

Background
With the growth in the popularity of facial filler injections, increased numbers of severe adverse events, such as cerebral embolism, have been reported.

Objectives
The aim of this article was to summarize the clinical manifestations and proposed mechanisms of filler-induced cerebral embolism (FICE).

Methods
A literature review was performed with the search keywords “filler injection,” “hyaluronic acid,” “fat graft,” “cerebral infarction,” “cerebral embolism,” “stroke,” “cerebrovascular infarction,” “disorders of consciousness,” and “hemiplegia.”

Results
Among the 43 cases of FICE enrolled from 35 articles, 37 patients were female, and 6 were male. Twenty-nine of these patients had received fat grafting, and 12 hyaluronic acid injection. Most FICE patients had been injected in the glabella, followed by the temporal, forehead, and nasal areas. Among 30 patients injected under local anesthesia, 43.33% presented with neurologic symptoms during the procedure. The main symptoms were consciousness disorders and hemiplegia. Most of the embolization sites were in the middle cerebral artery, followed by frontal lobe infarction and anterior cerebral artery infarction. Three patients developed cerebral hemorrhage after embolism. Twenty-six patients presented with newly acquired vision loss. The management for FICE cases included embolectomy, thrombolysis, decompressive craniectomy, antiplatelet/anticoagulant therapy, and symptomatic and nutritional treatment. Nearly half of the patients recovered or exhibited improved neurologic manifestations but not visual loss. Five patients died.

Conclusions
FICE is a severe complication following facial filler injection. Careful prevention, timely identification, and treatment are crucial to decreasing the morbidity and mortality of FICE.

Level of Evidence: 4
Safety of a Protective Funnel in Primary Breast Augmentation: A Retrospective Analysis of 380 Multicenter Cases in the United States
Authors: Lombardo Aldo , Antonetti Alfred R , Studin Joel , Stile Frank , Giles Dudley , Healy Jeffrey , Kim Roy , Schierle Clark , Gupta Varun , Rios Luis 
Published: April 2021

Abstract

Background
Protective funnel devices are commonly used to deliver implants in primary breast augmentation (BA) yet there is a paucity of evidence-based data describing their safety in the literature.

Objectives
The purpose of this study was to assess the safety of protective funnels in primary BA within the first 30 days postoperatively.

Methods
This multicenter, Level 3 study retrospectively reviewed the surgical records of 380 consecutive patients (760 breasts) who underwent primary BA by 9 board-certified plastic surgeons using the iNPLANT Funnel (Proximate Concepts LLC, Allendale, NJ) for implant delivery between November 2019 and December 2020. Data were collected pertaining to demographics, implant information, surgery details, and postoperative complications.

Results
The mean patient age was 33 years and 76% of patients had a BMI &lt;25 kg/m2. Of this cohort, 11.4% were smokers, 0.8% had diabetes, and 83% were ASA Class 1. All patients received smooth implants with a median volume of 375 cc. A total of 8 (2.1%) complications were reported, including 3 hematomas (0.79%), 1 seroma (0.26%), and 1 superficial infection (0.26%). No patient required explantation. We identified ASA class, BMI, surgery duration, and implant size as potential risk factors.

Conclusions
The data suggest that the use of protective funnels, such as the iNPLANT Funnel, in primary BA is a safe option when these are utilized according to the manufacturer’s Instructions for Use. The use of this device led to a low infection rate (0.26%) and a complication rate of (2.1%) consistent with the average reported in the literature (2%-2.5%).1 Implications for clinical practice are encouraging and future research will include a prospective analysis with a larger case series and potentially a control group.

Level of Evidence: 3
Low glucose and high pyruvate reduce the production of 2-oxoaldehydes, improving mitochondrial efficiency, redox regulation, and stallion sperm function†
Authors: Ortiz-Rodríguez José M , Martín-Cano Francisco E , Gaitskell-Phillips Gemma L , Silva Antonio , Ortega-Ferrusola Cristina , Gil María C , Peña Fernando J 
Published: April 2021

Abstract
Energy metabolism in spermatozoa is complex and involves the metabolism of carbohydrate fatty acids and amino acids. The ATP produced in the electron transport chain in the mitochondria appears to be crucial for both sperm motility and maintaining viability, whereas glycolytic enzymes in the flagella may contribute to ATP production to sustain motility and velocity. Stallion spermatozoa seemingly use diverse metabolic strategies, and in this regard, a study of the metabolic proteome showed that Gene Ontology terms and Reactome pathways related to pyruvate metabolism and the Krebs cycle were predominant. Following this, the hypothesis that low glucose concentrations can provide sufficient support for motility and velocity, and thus glucose concentration can be significantly reduced in the medium, was tested. Aliquots of stallion semen in four different media were stored for 48 h at 18°C; a commercial extender containing 67 mM glucose was used as a control. Stallion spermatozoa stored in media with low glucose (1 mM) and high pyruvate (10 mM) (LG-HP) sustained better motility and velocities than those stored in the commercial extender formulated with very high glucose (61.7 ± 1.2% in INRA 96 vs 76.2 ± 1.0% in LG-HP media after 48 h of incubation at 18°C; P &lt; 0.0001). Moreover, mitochondrial activity was superior in LG-HP extenders (24.1 ± 1.8% in INRA 96 vs 51.1 ± 0.7% in LG-HP of spermatozoa with active mitochondria after 48 h of storage at 18°C; P &lt; 0.0001). Low glucose concentrations may permit more efficient sperm metabolism and redox regulation when substrates for an efficient tricarboxylic acid cycle are provided. The improvement seen using low glucose extenders is due to reductions in the levels of glyoxal and methylglyoxal, 2-oxoaldehydes formed during glycolysis; these compounds are potent electrophiles able to react with proteins, lipids, and DNA, causing sperm damage.
Histopathological risk factors for lymph node metastases in T1 colorectal cancer: meta-analysis
Authors: Ebbehøj A L , Jørgensen L N , Krarup P -M , Smith H G 
Published: April 2021

Abstract

Background
National screening programmes increase the proportion of T1 colorectal cancers. Local excision may be possible, but the risk of lymph node metastases (LNMs) could jeopardize long-term outcomes. The aim of the present study was to review the association between histopathological findings and LNMs in T1 colorectal cancer.

Methods
A systematic literature search was conducted using PubMed,Embase, and Cochrane online databases. Studies investigating the association between one or more histopathological factors and LNMs in patients who underwent resection for T1 colorectal cancer were included.

Results
Sixteen observational studies were included in the meta-analysis, including a total of 10 181 patients, of whom 1 307 had LNMs. Lymphovascular invasion (odds ratio (OR) 7.42; P &lt; 0.001), tumour budding (OR 4.00; P &lt; 0.001), depth of submucosal invasion, whether measured as at least 1000 µm (OR 3.53; P &lt; 0.001) or Sm2–3 (OR 2.12; P = 0.020), high tumour grade (OR 3.75; P &lt; 0.001), polypoid growth pattern (OR 1.59; P = 0.040), and rectal location of tumour (OR 1.36; P = 0.003) were associated with LNMs.

Conclusion
Distinct histopathological factors associated with nodal metastases in T1 colorectal cancer can aid selection of patients for local excision or major excisional surgery.
Virtual reality simulation in robot-assisted surgery: meta-analysis of skill transfer and predictability of skill
Authors: Schmidt M W , Köppinger K F , Fan C , Kowalewski K -F , Schmidt L P , Vey J , Proctor T , Probst P , Bintintan V V , Müller-Stich B -P , Nickel F 
Published: April 2021

Abstract

Background
The value of virtual reality (VR) simulators for robot-assisted surgery (RAS) for skill assessment and training of surgeons has not been established. This systematic review and meta-analysis aimed to identify evidence on transferability of surgical skills acquired on robotic VR simulators to the operating room and the predictive value of robotic VR simulator performance for intraoperative performance.

Methods
MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science were searched systematically. Risk of bias was assessed using the Medical Education Research Study Quality Instrument and the Newcastle–Ottawa Scale for Education. Correlation coefficients were chosen as effect measure and pooled using the inverse-variance weighting approach. A random-effects model was applied to estimate the summary effect.

Results
A total of 14 131 potential articles were identified; there were eight studies eligible for qualitative and three for quantitative analysis. Three of four studies demonstrated transfer of surgical skills from robotic VR simulators to the operating room measured by time and technical surgical performance. Two of three studies found significant positive correlations between robotic VR simulator performance and intraoperative technical surgical performance; quantitative analysis revealed a positive combined correlation (r = 0.67, 95 per cent c.i. 0.22 to 0.88).

Conclusion
Technical surgical skills acquired through robotic VR simulator training can be transferred to the operating room, and operating room performance seems to be predictable by robotic VR simulator performance. VR training can therefore be justified before operating on patients.
A systematic review of colorectal multidisciplinary team meetings: an international comparison
Authors: Fehervari M , Hamrang-Yousefi S , Fadel M G , Mills S C , Warren O J , Tekkis P P , Kontovounisios C 
Published: April 2021

AbstractBackgroundColorectal multidisciplinary teams (CR MDTs) were introduced to enhance the cancer care pathway and allow for early investigation and treatment of cancer. However, there are no ‘gold standards’ set for this process. The aim of this study was to review the literature systematically and provide a qualitative analysis on the principles, organization, structure and output of CR MDTs internationally.MethodsLiterature on the role of CR MDTs published between January 1999 and March 2020 in the UK, USA and continental Europe was evaluated. Historical background, structure, core members, education, frequency, patient-selection criteria, quality assurance, clinical output and outcomes were extracted from data from the UK, USA and continental Europe.ResultsForty-eight studies were identified that specifically met the inclusion criteria. The majority of hospitals held CR MDTs at least fortnightly in the UK and Europe by 2002 and 2005 respectively. In the USA, monthly MDTs became a mandatory element of cancer programmes by 2013. In the UK, USA and in several European countries, the lead of the MDT meeting is a surgeon and core members include the oncologist, specialist nurse, histopathologist, radiologist and gastroenterologist. There were differences observed in patient-selection criteria, in the use of information technology, MDT databases and quality assurance internationally.ConclusionCR MDTs are essential in improving the patient care pathway and should express clear recommendations for each patient. However, a form of quality assurance should be implemented across all MDTs.
Sex modifies APOE ε4 dose effect on brain tau deposition in cognitively impaired individuals
Authors: Yan Shaozhen , Zheng Chaojie , Paranjpe Manish D , Li Yanxiao , Li Weihua , Wang Xiuying , Benzinger Tammie L S , Lu Jie , Zhou Yun 
Published: April 2021

Abstract
Recent studies in cognitively unimpaired elderly individuals suggest that the APOE ε4 allele exerts a dosage-dependent effect on brain tau deposition. The aim of this study was to investigate sex differences in APOE ε4 gene dosage effects on brain tau deposition in cognitively impaired individuals using quantitative 18F-flortaucipir PET.
Preprocessed 18F-flortaucipir tau PET images, T1-weighted structural MRI, demographic information, global cortical amyloid-β burden measured by 18F-florbetapir PET, CSF total tau and phosphorylated tau measurements were obtained from the Alzheimer’s Disease Neuroimaging Initiative database. Two hundred and sixty-eight cognitively impaired individuals with 146 APOE ε4 non-carriers and 122 carriers (85 heterozygotes and 37 homozygotes) were included in the study. An iterative reblurred Van Cittert iteration partial volume correction method was applied to all downloaded PET images. Magnetic resonance images were used for PET spatial normalization. Twelve regional standardized uptake value ratios relative to the cerebellum were computed in standard space. APOE ε4 dosage × sex interaction effect on 18F-flortaucipir standardized uptake value ratios was assessed using generalized linear models and sex-stratified analysis.
We observed a significant APOE ε4 dosage × sex interaction effect on tau deposition in the lateral temporal, posterior cingulate, medial temporal, inferior temporal, entorhinal cortex, amygdala, parahippocampal gyrus regions after adjusting for age and education level (P &lt; 0.05). The medial temporal, entorhinal cortex, amygdala and parahippocampal gyrus regions retained a significant APOE ε4 dosage × sex interaction effect on tau deposition after adjusting for global cortical amyloid-β (P &lt; 0.05). In sex-stratified analysis, there was no significant difference in tau deposition between female homozygotes and heterozygotes (P &gt; 0.05). In contrast, male homozygotes standardized uptake value ratios were significantly greater than heterozygotes or non-carriers throughout all 12 regions of interest (P &lt; 0.05). Female heterozygotes exhibited significantly increased tau deposition compared to male heterozygotes in the orbitofrontal, posterior cingulate, lateral temporal, inferior temporal, entorhinal cortex, amygdala and parahippocampal gyrus (P &lt; 0.05). Results from voxel-wise analysis were similar to the ones obtained from regions of interest analysis.
Our findings indicate that an APOE ε4 dosage effect on brain region-specific tau deposition exists in males, but not females. These results have important clinical implications towards developing sex and genotype-guided therapeutics in Alzheimer’s disease and uncovers a potential explanation underlying differential APOE ε4-associated Alzheimer’s risk in males and females.
Integrative biochemical, proteomics and metabolomics cerebrospinal fluid biomarkers predict clinical conversion to multiple sclerosis
Authors: Probert Fay , Yeo Tianrong , Zhou Yifan , Sealey Megan , Arora Siddharth , Palace Jacqueline , Claridge Timothy D W , Hillenbrand Rainer , Oechtering Johanna , Leppert David , Kuhle Jens , Anthony Daniel C 
Published: April 2021

Abstract
Eighty-five percent of multiple sclerosis cases begin with a discrete attack termed clinically isolated syndrome, but 37% of clinically isolated syndrome patients do not experience a relapse within 20 years of onset. Thus, the identification of biomarkers able to differentiate between individuals who are most likely to have a second clinical attack from those who remain in the clinically isolated syndrome stage is essential to apply a personalized medicine approach. We sought to identify biomarkers from biochemical, metabolic and proteomic screens that predict clinically defined conversion from clinically isolated syndrome to multiple sclerosis and generate a multi-omics-based algorithm with higher prognostic accuracy than any currently available test. An integrative multi-variate approach was applied to the analysis of cerebrospinal fluid samples taken from 54 individuals at the point of clinically isolated syndrome with 2–10 years of subsequent follow-up enabling stratification into clinical converters and non-converters. Leukocyte counts were significantly elevated at onset in the clinical converters and predict the occurrence of a second attack with 70% accuracy. Myo-inositol levels were significantly increased in clinical converters while glucose levels were decreased, predicting transition to multiple sclerosis with accuracies of 72% and 63%, respectively. Proteomics analysis identified 89 novel gene products related to conversion. The identified biochemical and protein biomarkers were combined to produce an algorithm with predictive accuracy of 83% for the transition to clinically defined multiple sclerosis, outperforming any individual biomarker in isolation including oligoclonal bands. The identified protein biomarkers are consistent with an exaggerated immune response, perturbed energy metabolism and multiple sclerosis pathology in the clinical converter group. The new biomarkers presented provide novel insight into the molecular pathways promoting disease while the multi-omics algorithm provides a means to more accurately predict whether an individual is likely to convert to clinically defined multiple sclerosis.
High resolution structural and functional MRI of the hippocampus in young adults with Down syndrome
Authors: Koenig Katherine A , Oh Se-Hong , Stasko Melissa R , Roth Elizabeth C , Taylor H Gerry , Ruedrich Stephen , Wang Z Irene , Leverenz James B , Costa Alberto C S 
Published: April 2021

AbstractDown syndrome is the phenotypic consequence of trisomy 21, with clinical presentation including both neurodevelopmental and neurodegenerative components. Although the intellectual disability typically displayed by individuals with Down syndrome is generally global, it also involves disproportionate deficits in hippocampally-mediated cognitive processes. Hippocampal dysfunction may also relate to Alzheimer’s disease-type pathology, which can appear in as early as the first decade of life and becomes universal by age 40. Using 7-tesla MRI of the brain, we present an assessment of the structure and function of the hippocampus in 34 individuals with Down syndrome (mean age 24.5 years ± 6.5) and 27 age- and sex-matched typically developing healthy controls. In addition to increased whole-brain mean cortical thickness and lateral ventricle volumes (P &lt; 1.0 × 10−4), individuals with Down syndrome showed selective volume reductions in bilateral hippocampal subfields cornu Ammonis field 1, dentate gyrus, and tail (P &lt; 0.005). In the group with Down syndrome, bilateral hippocampi showed widespread reductions in the strength of functional connectivity, predominately to frontal regions (P &lt; 0.02). Age was not related to hippocampal volumes or functional connectivity measures in either group, but both groups showed similar relationships of age to whole-brain volume measures (P &lt; 0.05). Finally, we performed an exploratory analysis of a subgroup of individuals with Down syndrome with both imaging and neuropsychological assessments. This analysis indicated that measures of spatial memory were related to mean cortical thickness, total grey matter volume and right hemisphere hippocampal subfield volumes (P &lt; 0.02). This work provides a first demonstration of the usefulness of high-field MRI to detect subtle differences in structure and function of the hippocampus in individuals with Down syndrome, and suggests the potential for development of MRI-derived measures as surrogate markers of drug efficacy in pharmacological studies designed to investigate enhancement of cognitive function.
Effectiveness and Cardiac Safety of Bedaquiline-Based Therapy for Drug-Resistant Tuberculosis: A Prospective Cohort Study
Authors: Brust James C M , Gandhi Neel R , Wasserman Sean , Maartens Gary , Omar Shaheed V , Ismail Nazir A , Campbell Angela , Joseph Lindsay , Hahn Alexandria , Allana Salim , Hernandez-Romieu Alfonso C , Zhang Chenshu , Mlisana Koleka , Viljoen Charle A , Zalta Benjamin , Ebrahim Ismaeel , Franczek Meghan , Master Iqbal , Ramangoaela Limpho , te Riele Julian , Meintjes Graeme 
Published: April 2021

Abstract

Background
Bedaquiline improves treatment outcomes in patients with rifampin-resistant (RR) tuberculosis but prolongs the QT interval and carries a black-box warning from the US Food and Drug Administration. The World Health Organization recommends that all patients with RR tuberculosis receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published.

Methods
We conducted an observational cohort study of patients with RR tuberculosis from 3 provinces in South Africa who received regimens containing bedaquiline. We performed rigorous cardiac monitoring, which included obtaining electrocardiograms in triplicate at 4 time points during bedaquiline therapy. Participants were followed up until the end of therapy or 24 months. Outcomes included final tuberculosis treatment outcome and QT interval prolongation (QT prolongation), defined as any QT interval corrected by the Fridericia method (QTcF) &gt;500 ms or an absolute change from baseline (ΔQTcF) &gt;60 ms.

Results
We enrolled 195 eligible participants, of whom 40% had extensively drug-resistant tuberculosis. Most participants (97%) received concurrent clofazimine. Of the participants, 74% were cured or successfully completed treatment, and outcomes did not differ by human immunodeficiency virus status. QTcF continued to increase throughout bedaquiline therapy, with a mean increase (standard deviation) of 23.7 (22.7) ms from baseline to month 6. Four participants experienced a QTcF &gt;500 ms and 19 experienced a ΔQTcF &gt;60 ms. Older age was independently associated with QT prolongation. QT prolongation was neither more common nor more severe in participants receiving concurrent lopinavir-ritonavir.

Conclusions
Severe QT prolongation was uncommon and did not require permanent discontinuation of either bedaquiline or clofazimine. Close monitoring of the QT interval may be advisable in older patients.
Understanding the uneven geography of urban energy transitions: insights from Edmonton, Canada
Authors: Joshi Neelakshi , Agrawal Sandeep 
Published: April 2021

AbstractCities are important partners in developing solutions towards a low-carbon pathway. However, given the variation in geography, a need exists to study urban energy transitions through a nuanced approach that addresses space- and place-based factors. Based on document analysis and interviews with municipal employees and local energy experts in Edmonton, Canada, we explore how location and availability of energy sources, political territoriality, physical urban landscapes and social embeddedness of fossil fuels influence municipal energy transition. Results illustrate that while Edmonton is shaped by its fossil fuel geography, it is actively carving out its low-carbon future through a geographically rooted transition strategy.