bluuebunny/crossref_metadata_2025 huggingface dataset:
An inexpensive, simple and effective method of genome DNA fragmentation for NGS libraries
Authors: Kechin Andrey , Boldyreva Darya , Borobova Viktoriya , Boyarskikh Ulyana , Scherbak Sergey , Apalko Svetlana , Makarova Maria , Mosyakin Nikolay , Kaftyreva Lidia , Filipenko Maxim
Published: August 2021

Next-generation sequencing (NGS)-library preparation for whole-genome sequencing (WGS) starts with DNA fragmentation, and sonication is a physical approach used most often due to its simplicity and reproducibility. However, the commercially available Covaris instrument has a high price for both the device and consumables. Here, we describe our in-house method of DNA shearing by sonication with small (100–600 µm) glass beads and an ultrasonic bath. The fragmentation conditions were optimized for the bacterial WGS with ∼550-bp fragment size (the ultrasonic bath water temperature 5–10°C, glass beads 0.06 g, the fragmentation time 50 s) and for human DNA with ∼250 bp (fragmentation with the same parameters for 4 min). Fragmentation results were compared with the Covaris instrument for preparing several bacterial NGS libraries for Illumina NGS platforms by several characteristics. We obtained close mean fragment lengths (523–623 versus 480–646), similar mono- and dinucleotide specificity of shearing, and comparable indicators of read alignment and de novo assembly for both methods. Thus, the described method is a new fast, and effective DNA fragmentation approach that can be used in different WGS applications.
Shaping REDD+: Interactions between Bilateral and Multilateral Rulemaking
Authors: Recio María Eugenia
Published: August 2021

This article studies bilateral partnerships on reducing emissions from deforestation and forest degradation (REDD+), particularly those led by Norway, through the conceptual lens of legal diffusion. The article argues that rules created through such partnerships have significantly influenced rulemaking under the United Nations Framework Convention on Climate Change. It shows that bilaterally developed rules have spread to other countries beyond the original partners, particularly in respect of topics such as financial institutional structures and a results-based approach to REDD+. Reciprocal legal influence between multilateral and bilateral legal developments can further be seen in relation to other topics, such as monitoring, reporting and verification. The article shows that legal concepts related to REDD+ travelled in different directions, showcasing interactions between bilateral and multilateral arenas in the construction of international norms, as well as interactions between the law for environmental protection and development cooperation.
3D finite-element modeling of effective elastic properties for fracture density and multiscale natural fractures
Authors: Jian Shikai , Fu Li-Yun , Cao Chenghao , Han Tongcheng , Du Qizhen
Published: August 2021

Natural fractures are usually multiscale in size, orientations and distribution, resulting in complex anisotropic characteristics. Analytical methods for quantifying the associated effective elastic properties are based on some assumptions, such as dilute fracture concentration and regular-shaped fractures, which do not occur in actual reservoirs. Here, we conduct anisotropic finite-element modeling of effective elastic properties of complex fractured rocks using the least-square fitting method. The algorithm is developed for a 3D case and validated by classical effective medium theories for models with different fracture densities. The results of the 3D numerical method agree well with the theoretical predictions at low fracture density. The model also considers the interactions among fractures to calculate equivalent stiffness tensors at high fracture density. Three 2D fracture models are simulated to demonstrate the basic behavior of stress interactions and their effect on the overall elasticity under different fracture densities. We applied the developed model to 3D natural fractures built from a real outcrop, and we found that the fracturing pattern significantly affects the effective anisotropy properties. The resultant P-wave phase velocities as functions of the incidence angle and frequency are anisotropic. This study provides a great potential to calculate equivalent stiffness tensors and anisotropic properties of 3D multiscale natural fractures.
Reflective Willingness to Pay: Preferences for Sustainable Consumption in a Consumer Welfare Analysis
Authors: Inderst Roman , Thomas Stefan
Published: August 2021

Our starting point is the following simple but potentially underappreciated observation: When assessing willingness to pay (WTP) for hedonic features of a product, the results of such measurement are influenced by the context in which the consumer makes her real or hypothetical choice or in which the questions to which she replies are set (such as in a contingent valuation analysis). This observation is of particular relevance when WTP regards sustainability, the ‘non-use value’ of which does not derive from a direct (physical) sensation and where perceived benefits depend heavily on available information and deliberations. The recognition of such context sensitivity paves the way for a broader conception of consumer welfare (CW), and our proposed standard of ‘reflective WTP’ may materially change the scope for private market initiatives with regards to sustainability, while keeping the analytical framework within the realm of the CW paradigm. In terms of practical implications, we argue, for instance, that actual purchasing decisions may prove insufficient to measure consumer appreciation of sustainability, as they may rather echo learnt but unreflected heuristics and may be subject to the specific shopping context, such as heavy price promotions. Also, while preferences may reflect the current social norm, the latter may change considerably over time as more consumers adapt their behaviour.
DIGITAL MARKET DEFINITION IN THE EUROPEAN UNION, UNITED STATES, AND BRAZIL: PAST, PRESENT, AND FUTURE
Authors: Eben Magali , Robertson Viktoria H S E
Published: August 2021

Market definition is a core concept of competition law around the globe, including in the European Union, the United States, and Brazil. In all three jurisdictions, antitrust authorities are grappling with the challenges of digital markets, often dealing with the very same digital players. The provision of zero-price services, the multisided nature of many digital platforms, and the implementation of entire digital ecosystems all challenge traditional approaches to market definition. But where there are common problems, there is a potential for common solutions. Through a comparative analysis of decisional practice relating to these past, present, and future challenges of digital market definition, this contribution maps the common ground already achieved while highlighting remaining gaps and possible solutions: for zero-price services—the past—it shows how a consensus has emerged on the theory and possible tools to define markets for ‘free’ services. On multisided platforms—the present—it finds that no such consensus has been reached yet, but strides are currently being made in developing an overall framework. And on digital ecosystems, it analyses how this challenge of the future requires the development of a coherent approach that can be based on cross-jurisdictional insights from the past and present.
Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents
Authors: Fisher Brian T , Zaoutis Theoklis E , Xiao Rui , Wattier Rachel L , Castagnola Elio , Pana Zoi Dorothea , Fullenkamp Allison , Boge Craig L K , Ross Rachael K , Yildirim Inci , Palazzi Debra L , Danziger-Isakov Lara , Vora Surabhi B , Arrieta Antonio , Yin Dwight E , Avilés-Robles Martha , Sharma Tanvi , Tribble Alison C , Maron Gabriela , Berman David , Green Michael , Sung Lillian , Romero José , Hauger Sarmistha B , Roilides Emmanuel , Belani Kiran , Nolt Dawn , Soler-Palacin Pere , López-Medina Eduardo , Muller William J , Halasa Natasha , Dulek Daniel , Hussain Ibrahim Zaid Bin , Pong Alice , Hoffman Jill , Rajan Sujatha , Gonzalez Blanca E , Hanisch Benjamin , Aftandilian Catherine , Carlesse Fabianne , Abzug Mark J , Huppler Anna R , Salvatore Christine M , Ardura Monica I , Chakrabarti Arunaloke , Santolaya Maria E , Localio A Russell , Steinbach William J
Published: August 2021

Background

Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis.

Methods

This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups.

Results

Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was −7.1% points (95% CI: −13.1% to −2.4%), favoring echinocandins. The risk difference was −0.4% (95% CI: −7.5% to 6.7%) at 30 days.

Conclusions

In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents.

Clinical Trials Registration

NCT01869829.
Spatial statistics in star-forming regions: is star formation driven by column density alone?
Authors: Retter B , Hatchell J , Naylor T
Published: August 2021

Star formation is known to occur more readily where more raw materials are available. This is often expressed by a ‘Kennicutt–Schmidt’ relation where the surface density of young stellar objects (YSOs) is proportional to column density to some power, μ. The aim of this work was to determine if column density alone is sufficient to explain the locations of Class 0/I YSOs within Serpens South, Serpens Core, Ophiuchus, NGC 1333, and IC348, or if there is clumping or avoidance that would point to additional influences on the star formation. Using the O-ring test as a summary statistic, 95 per cent confidence envelopes were produced for different values of μ from probability models made using the Herschel column density maps. The YSOs were tested against four distribution models: the best estimate of μ for the region, μ = 0 above a minimum column density threshold, and zero probability elsewhere, μ = 1, and the power law that best represents the five regions as a collective, μ = 2.05 ± 0.20. Results showed that μ = 2.05 model was consistent with the majority of regions and, for those regions, the spatial distribution of YSOs at a given column density is consistent with being random. Serpens South and NGC 1333 rejected the μ = 2.05 model on small scales of ${\sim}0.15\, \mathrm{pc}$ which implies that small-scale interactions may be necessary to improve the model. On scales above 0.15 pc, the positions of YSOs in all five regions can be well described using column density alone.
MLTI-06. Surgical resection plus stereotactic radiosurgery versus SRS alone for large brain metastases: a comparative study
Authors: Gutierrez Enrique , Kalyvas Aristotelis , Villafuerte Conrad , Millar Barbara-Ann , Conrad Tatiana , Laperriere Normand , Bernstein Mark , Weiss Jessica , Zadeh Gelareh , Kongkham Paul , Shultz David
Published: August 2021

Purpose

Large brain metastases (BRM) are challenging to manage. Therapeutic options include Stereotactic Radiosurgery (SRS) or surgery (S) with adjuvant SRS. We sought to compare overall survival (OS), radionecrosis (RN), local failure (LF), pachymeningeal (PMD) and leptomeningeal (LMD) disease in patients treated with SRS vs. S+SRS.

Methods

We reviewed a prospective registry database from 2009 to 2020 and identified all patients with BRM (≥4cc in volume) treated with SRS or S+SRS. WBRT or SRS re-targeting the index lesion were censoring events. Survival percentages were calculated using the Kaplan-Meier method. Differences between groups were tested using the Cox proportional hazards model.

Results

383 patients were identified, 128 and 255 were treated with S+SRS and SRS, respectively. Median ages in the S+SRS and SRS groups were 62.2 (23.6–98.5) and 60.2 (20.2–97.4) (P 0.33). OS at 12 and 24 months was 69% and 41% vs 55% and 20% for the S+SRS and SRS groups, respectively hazard ratio (HR) 1.64 (1.23–2.18) (P<0.001). LF requiring salvage surgery at 12 and 24 months were 3% and 5% vs 8% and 10% for S+SRS and SRS groups, respectively (P 0.067). RN at 12 and 24 months were 9% and 17% vs 15% and 21% for S+SRS and SRS groups, respectively 1.32 HR (0.77–2.29) (P =0.32). PMD disease at 12 and 24 months were 16% and 21% vs 3% and 7% for S+SRS and SRS groups, respectively HR 0.26(0.12–0.56) (P < 0.001). LMD at 12 and 24 months were 4% and 6% vs 2% and 4% for S+SRS and SRS groups, respectively HR 0.73(0.25–2.17) (P 0.57).

Conclusion

Surgical resection plus SRS correlated with improved OS and a trend towards a decreased incidence of LF compared to SRS alone. However, patients treated with S experienced an increased incidence of PMD.
OTHR-14. An immunogenomic analysis of melanoma brain metastases (MBM) compared to extracranial metastases (ECM)
Authors: Kennedy Lucy Boyce , Van Swearingen Amanda E D , Sheng Jeff , Zhang Dadong , Qin Xiaodi , Lipp Eric , Kumar Swaminathan , Zhang Gao , Hanks Brent , Davies Michael , Owzar Kouros , Anders Carey K , Salama April K S
Published: August 2021

Background

MBM have a unique molecular profile compared to ECM.

Methods

We analyzed a previously published dataset from MD Anderson Cancer Center, including RNA-seq on surgically resected, FFPE MBM and ECM from the same patients. STAR pipeline was used to estimate mRNA abundance. DESeq2 package was used to perform differential gene expression (DGE) analyses. Pathway analysis was performed using Gene Set Enrichment Analysis (GSEA). Paired DGE and GSEA compared MBM vs. lymph node (LN) metastases (n = 16) and MBM vs. skin mets (n = 10). CIBERSORTx estimated relative abundance of immune cell types in MBM and ECM. GATK Mutect2 pipeline was used to call somatic mutations using paired normal tumor samples. Mutations were annotated using the Ensembl Variant Effect Predictor and visualized using the Maftools package in R.

RNA-seq was available on 54 human primary cutaneous melanomas (CM). Gene Ontology or KEGG Pathway analysis was performed using goana function of limma package in R.

Results

Paired GSEA found that autophagy pathways may be up-regulated in MBM vs. LN and MBM vs. skin mets. On a single-gene level, the most strongly up-regulated genes in autophagy pathways were GFAP and HBB. Fold changes in other autophagy-related genes were low and did not reach significance. Comparison between CM which recurred in brain vs. CM which did not recur identified up-regulation of autophagy pathways. CIBERSORTx identified an increased proportion of immune suppressive M2 macrophages compared to tumor suppressive M1 macrophages in MBMs and ECMs.

Conclusion

Up-regulation of autophagy pathways was observed in patient-matched MBM vs. LN and skin mets. This finding was driven by up-regulation of GFAP and HBB, which could reflect changes in the tumor microenvironment. Higher M2:M1 ratio may contribute to an immune suppressive tumor microenvironment and may be targetable. Validation of our findings in an independent Duke dataset is ongoing.
RADI-07. Individualized Nomogram for Predicting Survival of Patients with Brain Metastases after Stereotactic Radiosurgery
Authors: Wen Lei , Shan Changguo , Lai Mingyao , Zhou Zhaoming , Cai Linbo
Published: August 2021

Background

Given the increasing use of stereotactic radiosurgery (SRS) for brain metastases (BM), there is an emerging need for more precise assessment of survival outcomes after SRS, especially in the modern targeted therapy era.

Methods

Patients with BM and treated by SRS were eligible in this study. Primary endpoint was overall survival (OS). Cox models were used to identify independent prognostic factors. Survival predictive nomogram was developed and evaluated by Concordance-index (C-index), area under the curve (AUC) and calibration curve.

Results

From January 2016 to December 2019, a total of 356 BM patients were eligible. Median OS was 17.7 months (95%CI 15.5–19.9) and actual OS at 1- and 2-year measured 63.2% and 37.6%, respectively. Nomogram for OS was developed by incorporating four independent prognostic factors: Karnofsky Performance Score, cumulative tumor volume, driver gene mutation status and serum lactate dehydrogenase. The nomogram was validated in a separate cohort demonstrated a well calibration and good discriminative ability (C-index=0.780, AUC=0.784). The prognostic accuracy of the nomogram (0.792) was considerably enhanced compared with classical prognostic indices, i.e., GPA (0.708), RPA (0.587) and SIR (0.536). Kaplan-Meier curves showed significant difference of OS among stratified low-, median- and high-risk groups (P < .001).

Conclusion

In conclusion, we developed and validated an individualized prognostic nomogram by integrating physiological, volumetric, clinical chemistry and molecular biological surrogates. This nomogram, should be validated by independent external study, has a potential to facilitate more precise risk-stratifications to guide personalized treatment for BM.
RADI-14. Bevacizumab vs Laser Interstitial Thermal Therapy in radiation necrosis from brain metastases: a systematic review and meta-analysis
Authors: Palmisciano Paolo , Haider Ali S , Nwagwu Chibueze D , Wahood Waseem , Sagoo Navraj S , Aoun Salah G , Abdullah Kalil G , El Ahmadieh Tarek Y
Published: August 2021

Objective

Radiation necrosis (RN) represents a serious post-radiotherapy complication in patients with brain metastases. Bevacizumab and laser interstitial thermal therapy (LITT) are viable treatment options, but direct comparative data is scarce. We reviewed the literature to compare the two treatment strategies.

Methods

PubMed, EMBASE, Scopus, and Cochrane databases were searched. All studies of patients with RN from brain metastases treated with bevacizumab or LITT were included. Treatment outcomes were analyzed using indirect meta-analysis with random-effect modeling.

Results

Among the 18 studies included, 143 patients received bevacizumab and 148 underwent LITT. Both strategies were equally effective in providing post-treatment symptomatic improvement (P=0.187, I2=54.8%), weaning off steroids (P=0.614, I2=25.5%), and local lesion control (P=0.5, I2=0%). The mean number of lesions per patient was not statistically significant among groups (P=0.624). Similarly, mean T1-contrast-enhancing pre-treatment volumes were not statistically different (P=0.582). Patterns of radiological responses differed at 6-month follow-ups, with rates of partial regression significantly higher in the bevacizumab group (P=0.001, I2=88.9%), and stable disease significantly higher in the LITT group (P=0.002, I2=81.9%). Survival rates were superior in the LITT cohort, and statistical significance was reached at 18 months (P=0.038, I2=73.7%). Low rates of adverse events were reported in both groups (14.7% for bevacizumab and 12.2% for LITT).

Conclusion

Bevacizumab and LITT can be safe and effective treatments for RN from brain metastases. Clinical and radiological outcomes are mostly comparable, but LITT may relate to superior survival benefits in select patients. Further studies are required to identify the best patient candidates for each treatment group.
RADI-23. Exploring the optimal timing of routine initial surveillance MRI following treatment of brain metastases with stereotactic radiosurgery: a comparison of two approaches
Authors: Lin Timothy , Siu Catherine , Redmond Kristin , Jackson Christopher , Bettegowda Chetan , Lim Michael , Kleinberg Lawrence
Published: August 2021

Purpose

To measure the value of early initial surveillance MRI scans in patients with brain metastases undergoing stereotactic radiosurgery (SRS), as MRI scans are a significant cost and patient stressor.

Methods

We identified a retrospective cohort of patients with brain metastases treated with SRS and followed at a single institution with scheduled 6-week or 12-week initial surveillance MRI. Imaging interval was based on policy of different providers. Outcome measures included new/progressive lesions, salvage treatment, detection of new lesions before symptoms, and use of surgical resection.

Results

Two hundred patients were included: 100 consecutive patients scanned with 6-week and 12-week imaging. Eighty-seven and 74 patients in each group had available follow-up imaging and were analyzed. Median time to MRI was 6.7 weeks and 13.5 (p<.001). No difference in primary site, prior SRS, number of treated brain metastases, or use of targeted therapy/immune checkpoint inhibitors was detected. A lower percentage of patients with 6-week MRI had controlled extracranial disease at initial treatment (30% vs 47%,p=.003). Twenty-eight percent with 6-week MRI had findings concerning for new/progressive disease, compared to 47% with 3-month MRI (p=0.01). Fifteen percent (10/87) with 6-week MRI underwent intervention (i.e. SRS, whole brain radiotherapy, or surgery) compared to 34% (20/74) with 12-week MRI (p=0.004). Of patients receiving SRS, a higher percentage had new/worsening neurologic symptoms (45% vs 30%) at follow-up although a lower percentage had new lesions >1cm (20% vs 50%) when discovered. One patient in each group underwent surgical salvage.

Conclusion

While shorter 6-week interval MRI surveillance post-SRS may detect new/progressive disease less frequently than 12-week MRI surveillance intervals, short interval MRI may be more likely to detect new/progressive lesions before symptoms develop. Surgical salvage was uncommon with either schedule. Further study may identify a high-risk subgroup who would benefit from early surveillance.
SURG-10. The evolving role of neurosurgery for central nervous system metastases in the era of personalized medicine
Authors: Karschnia Philipp , Rhun Emilie Le , Grau Stefan J , Preusser Matthias , Soffietti Riccardo , van den Bent Martin , Vogelbaum Michael , von Baumgarten Louisa , Westphal Manfred , Weller Michael , Tonn Joerg-Christian
Published: August 2021

Background

Novel therapies translating into improved survival of patients with advanced cancer have emerged. The number of metastases in the central nervous system is therefore seen to increase. Neurosurgery assumes an expanding role within multi-disciplinary care structures for such patients.

Methods

We performed a comprehensive literature review on the current status of neurosurgery for brain metastases patients. Based on the extracted data, we developed a review from experts in the field on the role of brain metastasis surgery in the era of personalized medicine.

Results

Traditionally, three metastases were considered the cutoff to offer surgical resection. With respect to the clinical status, the resection of a symptomatic mass may nowadays be considered even in presence of multiple tumors in a multimodal setting: surgical resection of brain metastasis provides immediate relief from mass effect-related symptoms and histology in case of unknown primary tumor; surgery may help stabilizing the disease, thus enabling further therapy; and in situations where immunotherapy is considered and non-surgical management would require long-term steroid administration, surgery may also provide expeditious relief of edema and reduction of needs for steroids. In patients with multiple brain metastasis and mixed response to non-surgical therapy, tumor resampling may allow tissue analysis for expression of molecular tumor targets. In patients with leptomeningeal dissemination and consecutive hydrocephalus, ventriculo-peritoneal shunting improves quality of life but also allows for time to administer more therapy thus prolonging survival. Addressing the limited efficacy of many oncological drugs for brain metastases, clinical trial protocols in which surgical specimens are analyzed for pre-surgically administered agents may offer pharmacodynamic insights.

Conclusion

Comprehensive neurosurgical care will have to be an integral element of multi-disciplinary oncological centres providing care to patients with brain metastases to improve on therapy and tumour biology research.
Ten years after the start of the euro crisis: lessons for financial markets and macroeconomic policies
Authors: Banerjee Anindya , Kouretas Georgios P , Papadopoulos Athanasios P , Tavlas George S
Published: August 2021

The papers in this Special Issue take stock of the functioning of the euro area during its crisis, which encompassed mainly the years 2009–15. They address several questions. For example, what surprises did the euro crisis provide about our knowledge about monetary unions? Why were the interconnections between banking systems and fiscal positions so strong during the euro area crisis? In so doing, they contribute to a deeper understanding of the nature of Europe’s monetary union, the underpinnings of its crisis, and the changes that need to be made to the monetary union so that crises can be prevented in the future.
Formation of self-organizing functionally distinct Rho of plants domains involves a reduced mobile population
Authors: Sternberg Hasana , Buriakovsky Ella , Bloch Daria , Gutman Orit , Henis Yoav I , Yalovsky Shaul
Published: August 2021

Rho family proteins are central to the regulation of cell polarity in eukaryotes. Rho of Plants-Guanyl nucleotide Exchange Factor (ROPGEF) can form self-organizing polar domains following co-expression with an Rho of Plants (ROP) and an ROP GTPase-Activating Protein (ROPGAP). Localization of ROPs in these domains has not been demonstrated, and the mechanisms underlying domain formation and function are not well understood. Here we show that six different ROPs form self-organizing domains when co-expressed with ROPGEF3 and GAP1 in Nicotiana benthamiana or Arabidopsis (Arabidopsis thaliana). Domain formation was associated with ROP–ROPGEF3 association, reduced ROP mobility, as revealed by time-lapse imaging and Fluorescence Recovery After Photobleaching beam size analysis, and was independent of Rho GTP Dissociation Inhibitor mediated recycling. The domain formation depended on the ROPs’ activation/inactivation cycles and interaction with anionic lipids via a C-terminal polybasic domain. Coexpression with the microtubule-associated protein ROP effector INTERACTOR OF CONSTITUTIVELY ACTIVE ROP 1 (ICR1) revealed differential function of the ROP domains in the ability to recruit ICR1. Taken together, the results reveal mechanisms underlying self-organizing ROP domain formation and function.
Sleep in the lesser mouse-deer (Tragulus kanchil)
Authors: Lyamin Oleg I , Siegel Jerome M , Nazarenko Evgeny A , Rozhnov Viatcheslav V
Published: August 2021

The mouse-deer or chevrotains are the smallest of the ungulates and ruminants. They are characterized by a number of traits which are considered plesiomorphic for the Artiodactyla order. The objective of this study was to examine sleep in the lesser mouse-deer (Tragulus kanchil), which is the smallest in this group (body mass < 2.2 kg). Electroencephalogram, nuchal electromyogram, electrooculogram, and body acceleration were recorded in four adult mouse-deer females using a telemetry system in Bu Gia Map National Park in Vietnam. The mouse-deer spent on average 49.7 ± 3.0% of 24 h in non-rapid eye movement (NREM) sleep. REM sleep occupied 1.7 ± 0.3% of 24 h or 3.2 ± 0.5% of total sleep time. The average duration of REM sleep episodes was 2.0 ± 0.2 min, the average maximum was 5.1 ± 1.1 min, and the longest episodes lasted 8 min. NREM sleep occurred in sternal recumbency with the head held above the ground while 64.7 ± 6.4% of REM sleep occurred with the head resting on the ground. The eyes were open throughout most of the NREM sleep period. The mouse-deer displayed polyphasic sleep and crepuscular peaks in activity (04:00–06:00 and 18:00–19:00). The largest amounts of NREM occurred in the morning (06:00–09:00) and the smallest before dusk (at 04:00–06:00). REM sleep occurred throughout most of the daylight hours (08:00–16:00) and in the first half of the night (19:00–02:00). We suggest that the pattern and timing of sleep in the lesser mouse-deer is adapted to the survival of a small herbivorous animal, subject to predation, living in high environmental temperatures in the tropical forest undergrowth.
Lysyl oxidase interactions with transforming growth factor‐β during angiogenesis are mediated by endothelin 1
Authors: Grunwald Hagar , Hunker Kristina L. , Birt Isabelle , Lulu Chen , Aviram Rohtem , Zaffryar‐Eilot Shelly , Ganesh Santhi K. , Hasson Peleg
Published: August 2021

Crosstalk between multiple components underlies the formation of mature vessels. Although the players involved in angiogenesis have been identified, mechanisms underlying the crosstalk between them are still unclear. Using the ex vivo aortic ring assay, we set out to dissect the interactions between two key angiogenic signaling pathways, vascular endothelial growth factor (VEGF) and transforming growth factor β (TGFβ), with members of the lysyl oxidase (LOX) family of matrix modifying enzymes. We find an interplay between VEGF, TGFβ, and the LOXs is essential for the formation of mature vascular smooth muscle cells (vSMC)‐coated vessels. RNA sequencing analysis further identified an interaction with the endothelin‐1 pathway. Our work implicates endothelin‐1 downstream of TGFβ in vascular maturation and demonstrate the complexity of processes involved in generating vSMC‐coated vessels.
e-Learning in regional anesthesia
Authors: Prineas Stavros , Cuyx Lotte , Smet Jeroen
Published: August 2021

Purpose of review

To explore the role and impact of e-learning technologies on regional anesthesia.

Recent findings

21st century technologies, such as ‘smart’ medical appliances, personal computers, sophisticated apps, the ubiquitous Internet, and online ‘e-learning’ curricula, are having a powerful impact on anesthesia training: when we learn, what we learn, and how we learn. But is ‘new’ necessarily ‘better’? The answer will result from the application of developments in IT technology through the current vision of architects of future anesthesia training programs. This narrative review aims to summarize the recent developments in anesthesia e-learning, and to forecast trends using regional anesthesia as an example.

The review offers some recommendations to ensure that the blessings promised to human learning by this ‘Brave New Cyberworld’ do not become its nemesis.
Discharging select patients without an escort after ambulatory anesthesia: identifying return to baseline function
Authors: Walsh Michael T.
Published: August 2021

Purpose of review

The current standard of care requires ambulatory surgical patients to have an escort for discharge. Recent studies have started to challenge this dogma. Modern ultrashort acting anesthetics have minimal psychomotor effects after a couple of hours. Driving simulator performance and psychomotor testing return to baseline as soon as 1 h following propofol sedation.

Recent findings

Two recent reports of actual experience with thousands of patients found no increase in complications in patients who were discharged without escort or drove themselves from a sedation center. These studies suggest discharge without escort may be safe in select patients but a method to identify appropriate patients remains undefined.

A reliable test to document return of function might allow safe discharge without an escort. Currently, there is intense interest in developing reliable, inexpensive, easy to administer psychomotor function testing to improve workplace safety and legally define the effects of drugs on driving impairment. Future studies may be able to adapt this technology and develop a validated test for residual anesthetic impairment.
Surgical Management of Medial Discoid Meniscus in Pediatric and Adolescent Patients
Authors: Feroe Aliya G. , Hussain Zaamin B. , Stupay Kristen L. , Kocher Sophia D. , Williams Kathryn A. , Micheli Lyle J. , Kocher Mininder S.
Published: August 2021

Background:

Medial discoid meniscus (MDM) is an exceedingly rare anatomic abnormality that presents similarly to other meniscal pathologies. Symptomatic MDM is typically managed arthroscopically with mixed short-term and long-term outcomes, although the existing knowledge about MDM is limited. The purpose of this study was to describe the presentation and surgical treatment of MDM in pediatric and adolescent patients.

Methods:

Medical records of 12 knees with MDM in 8 pediatric and adolescent patients treated between 1991 and 2016 were reviewed retrospectively for patient characteristics, clinical manifestations, radiographic findings, operative techniques, and surgical outcomes.

Results:

Of the 446 knees diagnosed arthroscopically with discoid menisci, lateral discoid meniscus was noted in 434 knees (97.3%) and MDM was present in 12 knees (2.7%). The MDM series included 8 patients of mean age 13.8 years (range: 7.8 to 19.8), of which 5 were males (63%), and 4 (50%) had bilateral involvement. Of the 11 knees with available clinical records, all cases presented symptomatically (pain, mechanical symptoms); 10 (91%) had concurrent physical exam findings. On intraoperative examination, discoid morphologies were described as complete in 4/8 knees (50%) or incomplete in 4/8 (50%), with associated instability in 6/12 (50%). Meniscal tears were reported in 9 cases (75%)—primarily, horizontal cleavage tears. Saucerization was performed in 11 knees (92%), with medial meniscal repair in 7 (58%), when indicated. Retear of the medial meniscus occurred in 4/11 knees (36%) at a mean of 25.8 months postoperation; 2 knees required revisions. One knee developed arthrofibrosis and underwent arthroscopic lysis of adhesions.

Conclusions:

MDM is a rare diagnosis, representing 3% of all discoid menisci, with a nonspecific clinical manifestation. Operative management of symptomatic MDM typically involves saucerization and meniscal repair, when indicated, for concurrent tears. Symptom resolution is common short-term, but long-term outcomes include recurrent meniscal tears. Subsequent observational studies are important to evaluate long-term outcomes, such as arthritic changes, with the advancement of arthroscopic techniques for meniscal preservation.

Level of Evidence:

Level IV—retrospective case series.
Cost-utility Analysis Comparing Bracing Versus Observation for Skeletally Immature Patients with Thoracic Scoliosis
Authors: Ikwuezunma Ijezie , Wang Kevin , Margalit Adam , Sponseller Paul , Jain Amit
Published: August 2021

Study Design.

Cost-utility analysis.

Objective.

This study aimed to investigate the cost-utility of bracing versus observation in patients with thoracic scoliosis who would be indicated for bracing.

Summary of Background Data.

There is high-quality evidence that bracing can prevent radiographic progression of spinal curvature in adolescent idiopathic scoliosis (AIS) patients with curves between 25° and 40° and Risser 0 to 2 skeletal maturity index. However, to our knowledge, the cost-utility of bracing in AIS has not been established.

Methods.

A decision-analysis model comparing bracing versus observation was developed for a hypothetical 10-year old girl (Risser 0, Sanders 3) with a 35° main thoracic curve. We estimated the probability, cost, and quality-adjusted life years (QALY) for each node based on comprehensive review of the literature. Costs were adjusted for inflation based on Consumer Price Index and reported in terms of 2020 real dollars. Incremental net monetary benefit (INMB) was calculated based on a probabilistic sensitivity analysis using Monte Carlo simulations of 1000 hypothetical patients. One-way sensitivity analyses were performed by varying cost, probability, and QALY estimates.

Results.

Our decision-analysis model revealed that bracing was the dominant treatment choice over observation at $50,000/QALY willingness to pay threshold. In simulation analysis of a hypothetical patient cohort, bracing was associated with lower net lifetime costs ($60,377 ± $5,340 with bracing vs. $85,279 ± $4543 with observation) and higher net lifetime QALYs (24.1 ± 2.0 with bracing vs. 23.9 ± 1.8 with observation). Bracing was associated with an INMB of $36,093 (95% confidence interval $18,894–$55,963) over observation over the patient's lifetime. The model was most sensitive to the impact of bracing versus observation on altering the probability of requiring surgery, either as an adolescent or an adult.

Conclusion.

Cost-utility analysis supports scoliosis bracing as the preferred choice in management of appropriately indicated AIS patients with thoracic scoliosis.

Level of Evidence: 5
Patient Characteristics, Injury Types, and Costs Associated with Secondary Over-Triage of Isolated Cervical Spine Fractures
Authors: Wick Joseph , Le Hai , Wick Katherine , Peddada Kranti , Bacon Adam , Han Gloria , Carroll Trevor , Swinford Steven , Javidan Yashar , Roberto Rolando , Martin Allan , Ebinu Julius , Kim Kee , Klineberg Eric
Published: August 2021

Study Design.

Retrospective cohort.

Objective.

To aim of this study was to identify patient variables, injury characteristics, and costs associated with operative and non-operative treatment following inter-facility transfer of patients with isolated cervical spine fractures.

Summary of Background Data.

Patients with isolated cervical spine fractures are subject to inter-facility transfer for surgical assessment, yet are often treated nonoperatively. The American College of Surgeons’ benchmark rate of “secondary over-triage” is <50%. Identifying patient and injury characteristics as well as costs associated with treatment following transfer of patients with isolated cervical spine fractures may help reduce rates of secondary over-triage and healthcare expenditures.

Methods.

Patients transferred to a Level-1 trauma center with isolated cervical spine fractures between January 2015 and September 2020 were identified. Patient demographics, comorbidities, insurance data, injury characteristics, imaging workup, treatment, and financial data were collected for all patients. Multivariable logistic regression models were constructed to identify patient and injury characteristics associated with surgical treatment.

Results.

Nearly 75% of patients were treated non-operatively. Over 97% of transfers were accepted by the general surgery trauma service. Multivariable modeling found that higher BMI, presence of any neurologic deficit including spinal cord or isolated spinal nerve root injuries, present smoking status, or cervical spine magnetic resonance imaging obtained post-transfer, were associated with surgical treatment for isolated cervical spine fractures. Among patients with type II dens fractures, increased fracture displacement was associated with surgical treatment. Median charges to patients treated operatively and nonoperatively were $380,890 and $90,734, respectively. Median hospital expenditures for patients treated operatively and nonoperatively were $55,115 and $12,131, respectively.

Conclusion.

A large proportion of patients with isolated cervical spine fractures are subject to over-triage. Injury characteristics are important for determining need for surgical treatment, and therefore interfacility transfer. Improving communication with spine surgeons when deciding to transfer patients may significantly reduce health care costs and resource use.

Level of Evidence: 4
PEEK Versus Titanium Static Interbody Cages
Authors: Canseco Jose A. , Karamian Brian A. , Patel Parthik D. , Divi Srikanth N. , Timmons Tyler , Hallman Haydn , Nachwalter Ryan , Lee Joseph K. , Kurd Mark F. , Anderson D. Greg , Rihn Jeffrey A. , Hilibrand Alan S. , Kepler Christopher K. , Vaccaro Alexander R. , Schroeder Gregory D.
Published: August 2021

Study Design:

This was a retrospective cohort study.

Objective:

This study evaluates the patient-reported Health Related Quality of Life outcomes and radiographic parameters of patients who underwent a single level transforaminal lumbar interbody fusion with either a polyetheretherketone (PEEK) or titanium interbody cage.

Summary of Background Data:

Spinal stenosis with instability is a common diagnosis that is often treated with interbody fusion, in particular transforaminal lumbar interbody fusion. Titanium and PEEK interbody cage properties have been extensively studied to understand their effect on fusion rates and subsidence.

Materials and Methods:

A retrospective cohort study was conducted from a single, high volume, academic hospital. Health Related Quality of Life outcomes were obtained from Outcomes Based Electronic Research Database and electronic medical record chart review. Subsidence was defined as a loss of 2 mm or more in the anterior or posterior disk height. Spinopelvic alignment parameters measured were sacral slope, pelvic tilt, pelvic incidence, lumbar lordosis, segmental lordosis, and pelvic incidence-lumbar lordosis mismatch. Fusion rates were assessed by the Brantigan-Steffee criteria.

Results:

The study included a total of 137 patients (108 PEEK, 29 titanium). Overall, no significant changes were noted between the 2 groups at 3 month or 1-year follow-up. Perioperatively, patients did report improvement in all outcome parameters within the PEEK and titanium groups. No significant difference was noted in subsidence rate between the 2 groups. Segmental lordosis significantly increased within the PEEK (+4.8 degrees; P<0.001) and titanium (+4.6 degrees; P=0.003) cage groups, however no difference was noted between groups. No significant difference was noted in fusion between the PEEK and titanium cage cohorts (92.6% vs. 86.2%; P=0.36).

Conclusion:

Overall, while PEEK and titanium cages exhibit unique biomaterial properties, our study shows that there were no significant differences with respect to patient-reported outcomes or radiographic outcomes between the 2 groups at the 1-year follow-up time point.

Level of Evidence:

Level III.
Unassisted Return of Spontaneous Circulation Following Withdrawal of Life-Sustaining Therapy During Donation After Circulatory Determination of Death in a Child
Authors: Zier Judith L. , Newman Nicole A.
Published: August 2021

OBJECTIVES:

To describe the unassisted return of spontaneous circulation following withdrawal of life-sustaining treatment in a child.

DESIGN:

Case report based on clinical observation and medical record review.

SETTING:

Community Children’s Hospital.

PATIENT:

Two-year old child.

INTERVENTIONS:

Following hypoxic-ischemic brain injury, the child was taken to the operating room for withdrawal of life-sustaining treatment during controlled donation after circulatory determination of death.

MEASUREMENTS AND MAIN RESULTS:

In addition to direct observation by experienced pediatric critical care providers, the child was monitored with electrocardiography, pulse oximetry, and invasive blood pressure via femoral arterial catheter in addition to direct observation by experienced pediatric critical care providers. Unassisted return of spontaneous circulation occurred greater than 2 minutes following circulatory arrest and was accompanied by return of respiration.

CONCLUSIONS:

We provide the first report of unassisted return of spontaneous circulation following withdrawal of life-sustaining treatment in a child. In our case, return of spontaneous circulation occurred in the setting of controlled donation after circulatory determination of death and was accompanied by return of respiration. Return of spontaneous circulation greater than 2 minutes following circulatory arrest in our patient indicates that 2 minutes of observation is insufficient to ensure that cessation of circulation is permanent after withdrawal of life-sustaining treatment in a child.
Eosinophilic Myocarditis: When Allergies Attack the Heart!
Authors: Jain Vardhmaan , Bansal Agam , Aggarwal Devika , Chetrit Michael , Gupta Manasvi , Bhatia Kirtipal , Thakkar Samarthkumar , Doshi Rajkumar , Ghosh Raktim , Bandopadhyay Dhrubajyoti , Barzilai Benico , Shiau Carolyn Jane , Frishman William H. , Aronow Wilbert S.
Published: August 2021

Eosinophilic myocarditis is a clinical condition whereby myocardial injury is mediated by eosinophilic infiltration. A number of underlying causes, including reactive, clonal, or idiopathic hypereosinophilic syndrome, may trigger eosinophilia. Disease presentation may vary from mild subclinical variants to fulminant myocarditis with thromboembolic complications, and in some cases, endomyocardial and valvular fibrosis may be seen. A detailed examination coupled with the use of multimodality imaging, and endomyocardial biopsy may help establish diagnosis. Treatment is aimed at symptomatic management and treating the underlying cause of eosinophilia, such as withdrawal of implicated drugs, antihelminthic therapy for infection, immunosuppression for autoimmune conditions, and targeted therapy with tyrosine kinase inhibitors in cases with clonal myeloid disorders.
Protopanaxadiol and Protopanaxatriol Ginsenosides Can Protect Against Aconitine-induced Injury in H9c2 Cells by Maintaining Calcium Homeostasis and Activating the AKT Pathway
Authors: Zhao Yan , Wang Haohao , He Chunyan , Zhang Shengbo , Wang Yu , Wang Yingping , Li Pingya , Liu Jinping
Published: August 2021

This study aimed to investigate the effects of protopanaxadiol and protopanaxatriol ginsenosides on aconitine-induced cardiomyocyte injury and their regulatory mechanisms. The effects of ginsenosides on aconitine-induced cardiomyocyte damage were initially evaluated using H9c2 cells, and the molecular mechanisms were elucidated using molecular docking and western blotting. The changes in enzyme content, reactive oxygen species (ROS), calcium (Ca2+) concentration, and apoptosis were determined. Furthermore, an aconitine-induced cardiac injury rat model was established, the cardiac injury and serum physiological and biochemical indexes were measured, and the effects of ginsenoside were observed. The results showed that ginsenoside Rb1 significantly increased aconitine-induced cell viability, and its binding conformation with protein kinase B (AKT) protein was the most significant. In vitro and in vivo, Rb1 protects cardiomyocytes from aconitine-induced injury by regulating oxidative stress levels and maintaining Ca2+ concentration homeostasis. Moreover, Rb1 activated the PI3K/AKT pathway, downregulated Cleaved caspase-3 and Bax, and upregulated Bcl-2 expression. In conclusion, Rb1 protected H9c2 cells from aconitine-induced injury by maintaining Ca2+ homeostasis and activating the PI3K/AKT pathway to induce a cascade response of downstream proteins, thereby protecting cardiomyocytes from damage. These results suggested that ginsenoside Rb1 may be a potential cardiac protective drug.