bluuebunny/crossref_metadata_2025 huggingface dataset:
Printable Graphene–Insulator–Semiconductor (GIS) Heterostructures for Active Control of Infrared Q‐Switched Laser
Authors: Dai Tengfei , Chang Jianhua , Li Hongxu , Chen Sian , Liu Haiyang , Xia Youlin , Peng Zheng , Tao Zhi , Hu Hai , Liu Xiang
Published: March 2021

2D materials have recently attracted extensive attention in solid‐state laser devices due to the improvement of their beam quality and service life. However, most conventional devices suffer from the fixed saturable absorption properties of certain 2D materials and are confined to the determined operation state. Herein, on‐chip electrically tunable infrared laser signals are realized by introducing a novel 2D nanomesh saturable absorber (SA) interaction layer without other tuning elements based on printable graphene–insulator–semiconductor (GIS) heterostructures. The pulse width can be highly controllable ranging from 1 µs to 360 ns under ultralow electrical modulation power (≈10 pA current and <0.5 nW power), thanks to the high conductivity and tunability of graphene. Furthermore, the precise regulation mechanism of the Fermi level of graphene by the heterostructures is comprehensively explored through opto‐electrical characterization with spectroscopic methods. The GIS device introduces a promising way to achieve actively controlled solid‐state optoelectronic and nonlinear photonic devices in the future.
Selective Endothelial Hyperactivation of Oncogenic KRAS Induces Brain Arteriovenous Malformations in Mice
Authors: Park Eun S. , Kim Sehee , Huang Shuning , Yoo Ji Young , Körbelin Jakob , Lee Tae Jin , Kaur Balveen , Dash Pramod K. , Chen Peng R. , Kim Eunhee
Published: March 2021

Objective

Brain arteriovenous malformations (bAVMs) are a leading cause of hemorrhagic stroke and neurological deficits in children and young adults, however, no pharmacological intervention is available to treat these patients. Although more than 95% of bAVMs are sporadic without family history, the pathogenesis of sporadic bAVMs is largely unknown, which may account for the lack of therapeutic options. KRAS mutations are frequently observed in cancer, and a recent unprecedented finding of these mutations in human sporadic bAVMs offers a new direction in the bAVM research. Using a novel adeno‐associated virus targeting brain endothelium (AAV‐BR1), the current study tested if endothelial KRASG12V mutation induces sporadic bAVMs in mice.

Methods

Five‐week‐old mice were systemically injected with either AAV‐BR1‐GFP or ‐KRASG12V. At 8 weeks after the AAV injection, bAVM formation and characteristics were addressed by histological and molecular analyses. The effect of MEK/ERK inhibition on KRASG12V‐induced bAVMs was determined by treatment of trametinib, a US Food and Drug Administration (FDA)‐approved MEK/ERK inhibitor.

Results

The viral‐mediated KRASG12V overexpression induced bAVMs, which were composed of a tangled nidus mirroring the distinctive morphology of human bAVMs. The bAVMs were accompanied by focal angiogenesis, intracerebral hemorrhages, altered vascular constituents, neuroinflammation, and impaired sensory/cognitive/motor functions. Finally, we confirmed that bAVM growth was inhibited by trametinib treatment.

Interpretation

Our innovative approach using AAV‐BR1 confirms that KRAS mutations promote bAVM development via the MEK/ERK pathway, and provides a novel preclinical mouse model of bAVMs which will be useful to develop a therapeutic strategy for patients with bAVM. ANN NEUROL 2021;89:926–941
Development of a Pteris vittata L. compound database by widely targeted metabolomics profiling
Authors: Nguyen Thi Kieu‐Oanh , Nguyen Ngoc‐Lien , Pham Hoang‐Nam , Sawada Yuji , Hirai Masami Yokota , Dauwe Rebecca , Dijoux‐Franca Marie‐Geneviève
Published: March 2021

The objective of this work was the development of a detailed, extensive and reliable database of the metabolomes of P. vittata. Using an ultra‐performance liquid chromatography–triple quadrupole tandem mass spectrometry system (UPLC‐QqQ‐MS/MS) and based on the knowledge of retention time and mass spectral characteristics of an in‐house collection of authentic standards, we screened for the presence of a large collection of natural compounds. The database represents 359 authenticated metabolites, comprising 220 primary and 139 secondary metabolites (70 flavonoids, 16 phenylpropanoic acid derivatives, five coumarins, two stilbenoids, 14 benzoic acids, nine phenols, 20 alkaloids and three terpenoids). Comparison of the accumulation of these compounds in two tissues showed that the aerial parts were enriched in flavonols, whereas the subterranean parts were enriched in anthocyanins. The comprehensive database developed here will be beneficial in improving the understanding of the chemical basis of plant therapeutic profile using multivariate analysis, with a particular example of antioxidant activity.
4‐Methylumbelliferone promotes the migration and odontogenetic differentiation of human dental pulp stem cells exposed to lipopolysaccharide in vitro
Authors: Chen Weiting , Guan Yun , Xu Fangfang , Jiang Beizhan
Published: March 2021

Hyaluronic acid (HA), a major component of the extracellular matrix, is essential to inflammatory regulation. 4‐Methylumbelliferone (4‐mu), as the specific inhibitor of HA synthesis, is an anti‐inflammatory in multiple systems. However, there have been no studies, to our knowledge, regarding 4‐mu treatment in pulp inflammation. Therefore, the purpose of this study was to investigate the effects of 4‐mu on biological behaviors in human dental pulp stem cells (hDPSCs) exposed to lipopolysaccharide (LPS) in vitro. hDPSCs were exposed to LPS to construct the inflammation model in vitro. Immunocytochemistry, quantitative polymerase chain reaction, western blotting, Cell Counting Kit‐8, scratch/Transwell assay, and alizarin red staining/alkaline phosphatase staining were selected to explore the effect of 4‐mu on the expression of inflammatory factors, cell proliferation, cell migration, and the odontogenic differentiation ability of hDPSCs. LPS stimulated hDPSCs to highly express the related inflammatory factors and CD44 (the major HA receptor), which were all inhibited by 0.1 mM of 4‐mu. In addition, the cell proliferation ability of hDPSCs was suppressed by 4‐mu, while cell migration and odontogenic differentiation abilities were significantly improved under inflammation. In conclusion, 4‐mu suppressed inflammatory cytokines in inflamed hDPSCs and had a positive effect on the migration and odontogenic differentiation of hDPSCs.
Mitochondrial iron and calcium homeostasis in Friedreich ataxia
Authors: Tamarit Jordi , Britti Elena , Delaspre Fabien , Medina‐Carbonero Marta , Sanz‐Alcázar Arabela , Cabiscol Elisa , Ros Joaquim
Published: March 2021

Friedreich Ataxia is a neuro‐cardiodegenerative disease caused by the deficiency of frataxin, a mitochondrial protein. Many evidences indicate that frataxin deficiency causes an unbalance of iron homeostasis. Nevertheless, in the last decade many results also highlighted the importance of calcium unbalance in the deleterious downstream effects caused by frataxin deficiency. In this review, the role of these two metals has been gathered to give a whole view of how iron and calcium dyshomeostasys impacts on cellular functions and, as a result, which strategies can be followed to find an effective therapy for the disease.
COVID‐19 and Moroccan nursing students: A multicentre cross‐sectional survey on their related knowledge, attitudes and practices
Authors: Fakhri Nada , Jallal Manar , Belabbes Sanaa , Khudur Khulud , Kaddar Rochdi , Oubaasri Ahmed , Elhadraoui Najia , Mohammed Abdallahi Ndjoubnane , Al Hassani Wafaa , Nejjari Chakib , Belouali Radouane , Khalis Mohamed
Published: March 2021

Aim

To assess knowledge, attitudes and practices of Moroccan nursing students towards COVID‐19.

Design

Cross‐sectional study.

Method

Data were collected using an online questionnaire consisted of demographic characteristics and 24 items about COVID‐19‐related knowledge, attitudes and practices.

Results

A total of 1,216 nursing students participated in this study. About 82% of the participants reported that the COVID‐19 virus spreads via respiratory droplets of infected individuals. The most clinical symptoms of COVID‐19 correctly identified by participants were fever (97.6%), dry cough (92.4%), dyspnoea (82%) and fatigue (74.9%). More than 56.6% of the participants were afraid of being affected by COVID‐19. Almost all participants reported that they avoid crowded places frequently. About 93.4% of the participants declared frequently wearing face mask when leaving home, and 85.5% maintained social distancing frequently. However, only 47.4% reported that they frequently washed their hands. About 51% stated that coronavirus outbreak has considerably changed their daily routines.
De-Escalated Adjuvant Therapy After Transoral Robotic Surgery for Human Papillomavirus-Related Oropharyngeal Carcinoma: The Sinai Robotic Surgery (SIRS) Trial
Authors: Miles Brett A. , Posner Marshall R. , Gupta Vishal , Teng Marita S. , Bakst Richard L. , Yao Mike , Misiukiewicz Kryzsztof J. , Chai Raymond L. , Sharma Sonam , Westra William H. , Kim-Schulze Seunghee , Dayal Bheesham , Sobotka Stanislaw , Sikora Andrew G. , Som Peter M. , Genden Eric M.
Published: March 2021

Background

Treatment of human papillomavirus-related oropharyngeal squamous cell carcinoma (HPVOPC) results in unprecedented high survival rates but possibly unnecessary toxicity. We hypothesized that upfront surgery and neck dissection followed by reduced-dose adjuvant therapy for early and intermediate HPVOPC would ultimately result in equivalent progression-free survival (PFS) and overall survival while reducing toxicity.

Methods

This study was a nonrandomized phase II trial for early-stage HPVOPC treated with transoral robotic surgery (TORS) followed by reduced-dose radiotherapy. Patients with previously untreated p16-positive HPVOPC and <20 pack years’ smoking history were enrolled. After robotic surgery, patients were assigned to group 1 (no poor risk features; surveillance), group 2 (intermediate pathologic risk factors [perineural invasion, lymphovascular invasion]; 50-Gy radiotherapy), or group 3 (poor prognostic pathologic factors [extranodal extension [ENE], more than three positive lymph nodes and positive margin]; concurrent 56-Gy chemoradiotherapy with weekly cisplatin).

Results

Fifty-four patients were evaluable; there were 25 in group 1, 15 in group 2, and 14 in group 3. Median follow-up was 43.9 months (9.6–75.8). Disease-specific survival was 98.1%, and PFS was 90.7%. PFS probability via Kaplan-Meier was 91.3% for group 1, 86.7% for group 2, and 93.3% for group 3. There were five locoregional failures (LRFs), including one distant metastasis and one contralateral second primary. Average time to LRF was 18.9 months (9.6–59.0); four LRFs were successfully salvaged, and the patients remain disease free (11.0–42.7 months); one subject remains alive with disease.

Conclusion

The results indicate that upfront surgery with neck dissection with reduced-dose radiation for T1–2, N1 stage (by the eighth edition American Joint Committee on Cancer staging manual) HPVOPC results in favorable survival with excellent function in this population. These results support radiation dose reduction after TORS as a de-escalation strategy in HPVOPC.

Implications for Practice

Transoral robotic surgery can provide a safe platform for de-escalation in carefully selected patients with early-stage human papillomavirus-related oropharyngeal cancer. In this clinical trial, disease-specific survival was 100%, over 90% of the cohort had a reduction of therapy from standard of care with excellent functional results, and the five patients with observed locoregional failures were successfully salvaged.
Effect of Potato Protein on Thermal and Rheological Characteristics of Maize Starches with Different Amylose Contents
Authors: Gałkowska Dorota , Dudycz Anna , Juszczak Lesław
Published: March 2021

The aim of this study is to evaluate the effect of potato protein (PP) on thermal and rheological characteristics of maize starches with different amylose contents. Samples are prepared by substituting 0, 1, 2, or 3 parts by weight of PP for 10 parts by weight of high amylose (HA), common (CM), or waxy (WM) maize starch. The PP has a different influence on the gelatinization characteristics of starch. Gelatinization enthalpy of the CM and WM starches increases from 12.08 to 21.76 J g–1 and from 16.95 to 25.62 J g–1, respectively, when the highest amount of the PP is used. Pasting temperature of the HA and CM starches decrease by 0.3–1.56 °C and 0.43–3.60 °C, respectively, while that of WM starch remains unchanged. The HA starch–PP pastes show higher final viscosity (736 × 10–3–2123 × 10–3 Pa s) than the starch‐only paste (580 × 10–3 Pa s). The starch‐protein pastes exhibit a shear‐thinning flow and a phenomenon of thixotropy. Substitution of the part of the HA or CM starch with the PP result in weakened viscoelastic structures of the produced gels, while the WM starch gel structure is strengthened. Results of the study may be useful in designing maize starch‐based foods supplemented with potato protein.
Patterns of invasive recurrence among patients originally treated for ductal carcinoma in situ by breast-conserving surgery versus mastectomy
Authors: Pawloski Kate R. , Tadros Audree B. , Sevilimedu Varadan , Newman Ashley , Gentile Lori , Zabor Emily C. , Morrow Monica , Van Zee Kimberly J. , Kirstein Laurie J.
Published: March 2021

Purpose

Local recurrence after treatment of ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) is more common than after mastectomy, but it is unclear if patterns of invasive recurrence vary by initial surgical therapy. Among patients with invasive recurrence after treatment for DCIS, we compared patterns of first recurrence between those originally treated with BCS vs. mastectomy.

Methods

From 2000 to 2016, women with an invasive recurrence occurring ≥ 6 months after initial treatment for DCIS were retrospectively identified. Clinicopathologic features and adjuvant treatment of the initial DCIS, as well as characteristics of first invasive recurrences, were compared between patients who had undergone BCS vs. mastectomy.

Results

452 patients with an invasive recurrence after surgery for DCIS were identified: 367 patients (81%) had initially undergone BCS and 85 patients (19%) mastectomy. Patients originally treated with mastectomy were younger and were more likely to have had high grade, necrosis, and multifocal or multicentric DCIS (p < 0.001) compared with the BCS group. A higher proportion of invasive recurrences were local after BCS (93%; 343/367), whereas 88% (75/85) of recurrences after mastectomy were regional or distant (p < 0.001). The median time to first invasive recurrence was not different between surgical groups (BCS: 6.4 years vs. mastectomy: 5.5 years; p = 0.12).

Conclusions

Among women who experienced a first invasive recurrence after treatment for DCIS, those who had originally undergone mastectomy more commonly presented with advanced disease compared to those treated with BCS, likely related to the absence of the breast and the higher risk profile of their initial DCIS.
Heart rate, intelligence in adolescence, and Parkinson’s disease later in life
Authors: Longinetti Elisa , Zhan Yiqiang , Sata Mizuki , Larsson Henrik , D′Onofrio Brian M. , Iso Hiroyasu , Wirdefeldt Karin , Fang Fang
Published: March 2021

To investigate whether physical and cognitive fitness measured in late adolescence was associated with future risk of Parkinson’s disease (PD). The cohort included 1,259,485 Swedish men with physical fitness, body mass index (BMI), resting heart rate (RHR), blood pressure, intelligence quotient (IQ), and stress resilience measured at the age of 17–20 in relation to conscription. Incident cases of PD were ascertained from the Swedish Patient Register. Hazard ratios were estimated from Cox models, after controlling for multiple confounders. We further performed Mendelian randomization (MR) analyses to assess the causality of the associations, using GWAS summary statistics with > 800,000 individuals. During follow-up, we identified 1,034 cases of PD (mean age at diagnosis = 53). Men with an RHR > 100 beats per minute had a higher risk of PD compared to men with an RHR of 60–100 beats per minute (HR = 1.47; 95% CI = 1.08–1.99). Men with IQ above the highest tertile had a higher risk of PD compared to men with an IQ below the lowest tertile (HR = 1.46; 95% CI = 1.19–1.79). We found no association for physical fitness, BMI, blood pressure, or stress resilience. A causal relationship was suggested by the MR analysis between IQ and PD, but not between RHR and PD. RHR and IQ in late adolescence were associated with a higher risk of PD diagnosed at relatively young age. The association of IQ with PD is likely causal, whereas the association of RHR with PD suggests that altered cardiac autonomic function might start before 20 years of age in PD.
A longitudinal study of e-commerce diversity in Europe
Authors: Sadowski Adam , Lewandowska-Gwarda Karolina , Pisarek-Bartoszewska Renata , Engelseth Per
Published: March 2021

Owing to increased access to the Internet and the development of electronic commerce, e-commerce has become a common method of shopping in all countries. The purpose of this study is more precisely to research e-commerce diversity in Europe at the regional level and develop the conception of “E-commerce Supply Chain Management”. Statistical data derived from the European Statistical Office were applied to analyse the spatial diversity of e-retailing. Assessments of the regional diversity of e-retailing applied geographic information systems and exploratory spatial data analysis methods such us global and local spatial autocorrelation statistics. Clusters of regions with similar household preferences related to online shopping were identified. A spatial visualisation of the e-retailing diversity phenomenon may be utilised for the reconfiguration of supply chains and to adapt them to actual household preferences related to shopping methods.
Parental Warmth and Hostility and the Development of Psychopathic Behaviors: A Longitudinal Study of Young Offenders
Authors: Backman Heidi , Laajasalo Taina , Jokela Markus , Aronen Eeva T.
Published: March 2021

Parental behaviors may shape levels of psychopathic traits and antisocial outcomes among youth. To better evaluate the potential causality of these associations, we used eight follow-ups from the Pathways to Desistance study of 1354 offending adolescents (14.3% female; 40.1% black) and examined whether within-individual variation in parenting over time was associated with within-individual variation in psychopathic traits and offending. Multilevel regression models were adjusted for age, gender, ethnicity, contact with parental figure, and self-reported offending. Adolescent self-reported parental warmth was associated with lower psychopathic traits, and parental hostility with higher psychopathic traits. The results indicated that the more supportive and nurturing the parent, the lower the levels of psychopathic traits, whereas the more hostile the parent, the higher the levels, respectively. In addition, self-reported offending was predicted by higher parental hostility and lower maternal warmth. In time-lagged analysis, psychopathic traits did not predict parental behaviors. In young offenders parental warmth may protect against development of psychopathic traits in adolescence, whereas parental hostility may strengthen these traits. We conclude, that parenting quality matters in adolescence. Warm parenting style at this developmental period associates with lower psychopathic features among young offenders possibly lowering the risk of further criminal activity.
Extending vegetation site data and ensemble models to predict patterns of foliage cover and species richness for plant functional groups
Authors: McNellie Megan J. , Oliver Ian , Ferrier Simon , Newell Graeme , Manion Glenn , Griffioen Peter , White Matt , Koen Terry , Somerville Michael , Gibbons Philip
Published: March 2021

Context

Ensembles of artificial neural network models can be trained to predict the continuous characteristics of vegetation such as the foliage cover and species richness of different plant functional groups.

Objectives

Our first objective was to synthesise existing site-based observations of native plant species to quantify summed percentage foliage cover and species richness within four functional groups and in totality. Secondly, we generated spatially-explicit, continuous, landscape-scale models of these functional groups, accompanied by maps of the model residuals to show uncertainty.

Methods

Using a case study from New South Wales, Australia, we aggregated floristic observations from 6806 sites into four common plant growth forms (trees, shrubs, grasses and forbs) representing four different functional groups. We coupled these response data with spatially-complete surfaces describing environmental predictors and predictors that reflect landscape-scale disturbance. We predicted the distribution of foliage cover and species richness of these four plant functional groups over 1.5 million hectares. Importantly, we display spatially explicit model residuals so that end-users have a tangible and transparent means of assessing model uncertainty.

Results

Models of richness generally performed well (R20.43–0.63), whereas models of cover were more variable (R20.12–0.69). RMSD ranged from 1.42 (tree richness) to 29.86 (total native cover). MAE ranged from 1.0 (tree richness) to 20.73 (total native foliage cover).

Conclusions

Continuous maps of vegetation attributes can add considerable value to existing maps and models of discrete vegetation classes and provide ecologically informative data to support better decisions across multiple spatial scales.
Convergence theorems on multi-dimensional homogeneous quantum walks
Authors: Sako Hiroki
Published: March 2021

We propose a general framework for quantum walks on d-dimensional spaces. We investigate asymptotic behavior of these walks. We prove that every homogeneous walks with finite degree of freedom have limit distribution. This theorem can also be applied to every crystal lattice. In this theorem, it is not necessary to assume that the support of the initial unit vector is finite. We also pay attention on 1-cocycles, which is related to Heisenberg representation of time evolution of observables. For homogeneous walks with finite degree of freedom, convergence of averages of 1-cocycles associated with the position observable is also proved.
Auroral “Dunes” Light Up Earth’s Atmosphere
Authors: Kornei Katherine
Published: March 2021

The auroral feature, first spotted by amateur astronomers in 2015, likely traces high-altitude atmospheric waves.
The Evidence Base for the Benefits of Functional Septorhinoplasty and its Future Post COVID-19
Authors: Unadkat Samit N. , Pendolino Alfonso Luca , Auer Deborah , Khwaja Sadie , Randhawa Premjit S. , Andrews Peter J. , Saleh Hesham A.
Published: March 2021

Ever since the introduction of the concept of Procedures of Limited Clinical Value (PoLCV), procedures such as functional septorhinoplasty have been subject to additional funding restrictions within the British National Health Service. Recent publications have suggested that 10% of Clinical Commissioning Groups in the United Kingdom no longer fund septorhinoplasty surgery irrespective of the indications, including congenital malformations or post-trauma, and despite the strong evidence available in the literature in treating a range of health conditions. Thus, inequity exists across the country. At present functional septorhinoplasty surgery is frequently but incorrectly grouped together with aesthetic rhinoplasty, both of which are deemed to be cosmetic interventions. Moreover, as we exit the peak of the current coronavirus disease 2019 (COVID-19) pandemic, procedures deemed to be of lower clinical priority will potentially be at risk throughout Europe. The purpose of this review is twofold; the first is to put forward the evidence to commissioners in favor of functional septorhinoplasty surgery on patient well-being and mental health; the second is to demonstrate why functional septorhinoplasty surgery is a distinct procedure from aesthetic rhinoplasty and why it ought not to be classified as a procedure of limited clinical value.
Increased beat-to-beat variability of cerebral microcirculatory perfusion during atrial fibrillation: a near-infrared spectroscopy study
Authors: Saglietto Andrea , Scarsoglio Stefania , Canova Daniela , Roatta Silvestro , Gianotto Nefer , Piccotti Alessandro , Franzin Simone , Gaita Fiorenzo , De Ferrari Gaetano Maria , Ridolfi Luca , Anselmino Matteo
Published: March 2021

Aims

Atrial fibrillation (AFib) is associated with cognitive decline/dementia, independently from clinical strokes or transient ischaemic attacks (TIA). Recent in silico data suggested that AFib may induce transient critical haemodynamic events in the cerebral microcirculation. The aim of this study is to use non-invasive spatially resolved cerebral near-infrared spectroscopy (SRS-NIRS) to investigate in vivo beat-to-beat microcirculatory perfusion during AFib and after sinus rhythm (SR) restoration.

Methods and results

Cerebral SRS-NIRS with high-frequency sampling (20 Hz) and non-invasive systemic haemodynamic monitoring were recorded before and after elective electrical cardioversion (ECV) for AFib or atrial flutter (AFL). To assess beat-to-beat effects of the rhythm status, the frequency distribution of inter-beat differences in tissue haemoglobin index (THI), a proxy of microcirculatory cerebral perfusion, was compared before and after SR restoration. Fifty-three AFib/AFL patients (mean age 69 ± 8 years, 79% males) were ultimately enrolled. Cardioversion was successful in restoring SR in 51 (96%) patients. In front of a non-significant decrease in arterial blood pressure extreme events between pre- and post-ECV measurements, a significant decrease of both hypoperfusive and hyperperfusive/hypertensive microcirculatory events was observed after SR restoration (P < 0.001 and P = 0.041, respectively).

Conclusion

The present is the first in vivo demonstration that SR restoration by ECV significantly reduces the burden of extreme single-beat haemodynamic events in cerebral microcirculation. Future studies are needed to assess whether SR maintenance might slow long-term AFib-correlated cognitive decline/dementia.
Research and Exploratory Analysis Driven—Time-data Visualization (read-tv) software
Authors: Del Gaizo John , Catchpole Ken R , Alekseyenko Alexander V
Published: March 2021

Motivation

Research & Exploratory Analysis Driven Time-data Visualization (read-tv) is an open source R Shiny application for visualizing irregularly and regularly spaced longitudinal data. read-tv provides unique filtering and changepoint analysis (CPA) features. The need for these analyses was motivated by research of surgical work-flow disruptions in operating room settings. Specifically, for the analysis of the causes and characteristics of periods of high disruption-rates, which are associated with adverse surgical outcomes.

Materials and Methods

read-tv is a graphical application, and the main component of a package of the same name. read-tv generates and evaluates code to filter and visualize data. Users can view the visualization code from within the application, which facilitates reproducibility. The data input requirements are simple, a table with a time column with no missing values. The input can either be in the form of a file, or an in-memory dataframe– which is effective for rapid visualization during curation.

Results

We used read-tv to automatically detect surgical disruption cascades. We found that the most common disruption type during a cascade was training, followed by equipment.

Discussion

read-tv fills a need for visualization software of surgical disruptions and other longitudinal data. Every visualization is reproducible, the exact source code that read-tv executes to create a visualization is available from within the application. read-tv is generalizable, it can plot any tabular dataset given the simple requirements that there is a numeric, datetime, or datetime string column with no missing values. Finally, the tab-based architecture of read-tv is easily extensible, it is relatively simple to add new functionality by implementing a tab in the source code.

Conclusion

read-tv enables quick identification of patterns through customizable longitudinal plots; faceting; CPA; and user-specified filters. The package is available on GitHub under an MIT license.
RETROPUPILLARY IRIS-CLAW INTRAOCULAR LENS AND PARS PLANA VITRECTOMY IN APHAKIA MANAGEMENT
Authors: Bernal-Morales Carolina , Hernández-Martínez Adrián , Navarro-Angulo Manuel J. , Ruiz-Miguel Miguel , Rodriguez-Maqueda Mariano , Velazquez-Villoria Daniel , Cubero-Parra Juan Manuel , Marticorena Joaquín , Ruiz-Casas Diego , Adan Alfredo , Zarranz-Ventura Javier ,   Writing Committee on behalf of the Spanish Multicenter Iris-claw IOL study group
Published: March 2021

Purpose:

To evaluate the outcomes and safety of retropupillary iris-claw intraocular lens implantation and associated pars plana vitrectomy.

Methods:

Multicenter, national audit of 325 eyes (325 patients). Demographics, surgical details, and complications are described. Visual acuity, intraocular pressure, and central retinal thickness assessed by optical coherence tomography were collected at 1, 3, 6, and 12 months after surgery. Kaplan–Meier curves were created to assess the cumulative probability of postoperative visual acuity and intraocular pressure levels, macular edema development, and corneal decompensation.

Results:

The cumulative probability of the final visual acuity ≤0.3 logarithm of the minimum angle of resolution (≥20/40 Snellen) was 75.6% at 12-month follow-up. The probability of intraocular pressure >21, ≥25, and ≥30 mmHg was 48.1%, 33.1%, and 19.0%, and the probability of intraocular pressure–lowering drops was 50.9% at 12 months. Glaucoma surgery was required in 4.3% of the eyes (14/325). The cumulative probability of macular edema was 20.5% at 12 months and was greater in complicated cataract surgery than in intraocular lens–luxation eyes (26% vs. 16.7%, P = 0.04). Corneal transplantation was required in 2.8% of the eyes (9/325).

Conclusion:

This study on 325 eyes with aphakia or intraocular lens dislocation managed with the retropupillary iris-claw intraocular lens technique provides clinical outcomes in a real-world scenario, reporting relevant data for patient counseling and preoperative discussions.
Feature Detection to Segment Cardiomyocyte Nuclei for Investigating Cardiac Contractility
Authors: Teranikar Tanveer , Villarreal Cameron , Salehin Nabid , Lim Jessica , Ijaseun Toluwani , Cao Hung , Chuong Cheng–Jen , Lee Juhyun
Published: March 2021

In vivoquantitative assessment of structural and functional biomarkers is essential for understanding pathophysiology and identifying novel therapies for congenital heart disorders. Cardiac defect analysis through fixed tissue and histology has offered revolutionary insights into the tissue architecture, but section thickness limits the tissue penetration. This study demonstrated the potential of Light Sheet Fluorescence Microscopy (LSFM) for analyzingin vivo4D (3d + time) cardiac contractility. Furthermore, we have described the utility of an improved feature detection framework for localizing cardiomyocyte nuclei in the zebrafish atrium and ventricle. Using the Hessian Difference of Gaussian (HDoG) scale space in conjunction with the watershed algorithm, we were able to quantify a statistically significant increase in cardiomyocyte nuclei count across different developmental stages.

Furthermore, we assessed individual volumes and surface areas for the cardiomyocyte nuclei in the ventricle’s innermost and outermost curvature during cardiac systole and diastole. Using the segmented nuclei volumes from the feature detection, we successfully performed local area ratio analysis to quantify the degree of deformation suffered by the outermost ventricular region compared to the innermost ventricular region. This paper focuses on the merits of our segmentation and demonstrates its efficacy for cell counting and morphology analysis in the presence of anisotropic illumination across the field-of-view (FOV).
A recombinant selective drug-resistantM. bovisBCG enhances the bactericidal activity of a second-line tuberculosis regimen
Authors: Chiwala Gift , Liu Zhiyong , Mugweru Julius N. , Wang Bangxing , Khan Shahzad Akbar , Bate Petuel Ndip Ndip , Yusuf Buhari , Hameed H.M. Adnan , Fang Cuiting , Tan Yaoju , Guan Ping , Hu Jinxing , Tan Shouyong , Liu Jianxiong , Zhong Nanshan , Zhang Tianyu
Published: March 2021

Drug-resistant tuberculosis (DR-TB) results from infection byMycobacterium tuberculosisstrains resistant to at least rifampin or isoniazid. To improve the treatment outcome in DR-TB, therapeutic vaccines are considered an ideal choice as they can enhance pathogen clearance and minimize disease sequelae. To date, there is no therapeutic vaccine reported to be effective when combined with a chemotherapy regimen against DR-TB. The only available TB vaccine, theM. bovisBCG (BCG) is susceptible to several anti-TB drugs hence not a perfect option for therapeutic vaccination. Herein, we developed a recombinant BCG (RdrBCG) overexpressing Ag85B and Rv2628 with resistance to selected anti-TB drugs. When administered three times adjunct to a second-line anti-TB regimen in a classical murine model of DR-TB, the RdrBCG lowered lungM. tuberculosiscolony-forming units by 1 log10. Furthermore, vaccination with the RdrBCG adjunct to TB chemotherapy minimized lung tissue pathology in mice. Most importantly, the RdrBCG maintained the exogenously inserted genes and showed almost the same virulence as its parent BCG Tice strain in severe combined immune-deficient mice. All these suggested that the RdrBCG was stable, safe and effective. Hence, the “recombinant” plus “drug-resistant” BCG strategy could be a useful concept for developing therapeutic vaccines against DR-TB.
Semaphorin3F Drives Dendritic Spine Pruning through Rho-GTPase Signaling
Authors: Duncan Bryce W. , Mohan Vishwa , Wade Sarah D. , Truong Young , Kampov-Polevoi Alexander , Temple Brenda R. , Maness Patricia F.
Published: March 2021

Dendritic spines of cortical pyramidal neurons are initially overproduced then remodeled substantially in the adolescent brain to achieve appropriate excitatory balance in mature circuits. Here we investigated the molecular mechanism of developmental spine pruning by Semaphorin 3F (Sema3F) and its holoreceptor complex, which consists of immunoglobulin-class adhesion molecule NrCAM, Neuropilin-2 (Npn2), and PlexinA3 (PlexA3) signaling subunits. Structure-function studies of the NrCAM-Npn2 interface showed that NrCAM stabilizes binding between Npn2 and PlexA3 necessary for Sema3F-induced spine pruning. Using a mouse neuronal culture system, we identified a dual signaling pathway for Sema3F-induced pruning, which involves activation of Tiam1-Rac1-PAK1-3 -LIMK1/2-Cofilin1 and RhoA-ROCK1/2-Myosin II in dendritic spines. Inhibitors of actin remodeling impaired spine collapse in the cortical neurons. Elucidation of these pathways expands our understanding of critical events that sculpt neuronal networks and may provide insight into how interruptions to these pathways could lead to spine dysgenesis in diseases such as autism, bipolar disorder, and schizophrenia.
Mechanistic within-host models of the asexualPlasmodium falciparuminfection: a review and analytical assessment
Authors: Camponovo Flavia , Lee Tamsin E. , Russell Jonathan , Burgert Lydia , Gerardin Jaline , Penny Melissa A.
Published: March 2021

Background

Malaria blood-stage infection length and intensity are important drivers of disease and transmission; however, the underlying mechanisms of parasite growth and the host’s immune response during infection remain largely unknown. Over the last 30 years, several mechanistic mathematical models of malaria parasite within-host dynamics have been published and used in malaria transmission models.

Methods

We identified mechanistic within-host models of parasite dynamics through a review of published literature. For a subset of these, we reproduced model code and compared descriptive statistics between the models using fitted data. Through simulation and model analysis, we compare and discuss key features of the models, including assumptions on growth, immune response components, variant switching mechanisms, and inter-individual variability.

Results

The assessed within-host malaria models generally replicate infection dynamics in malaria-naïve individuals. However, there are substantial differences between the model dynamics after disease onset, and models do not always reproduce late infection parasitemia data used for calibration of the within host infections. Models have attempted to capture the considerable variability in parasite dynamics between individuals by including stochastic parasite multiplication rates; variant switching dynamics leading to immune escape; variable effects of the host immune responses; or via probabilistic events. For models that capture realistic length of infections, model representations of innate immunity explain early peaks in infection density that cause clinical symptoms, and model representations of antibody immune responses control the length of infection. Models differed in their assumptions concerning variant switching dynamics, reflecting uncertainty in the underlying mechanisms of variant switching revealed by recent clinical data during early infection. Overall, given the scarce availability of the biological evidence there is limited support for complex models.

Conclusions

Our study suggests that much of the inter-individual variability observed in clinical malaria infections has traditionally been attributed in models to random variability, rather than mechanistic disease dynamics. Thus, we propose that newly developed models should assume simple immune dynamics that minimally capture mechanistic understandings and avoid over-parameterisation and large stochasticity which inaccurately represent unknown disease mechanisms.
A CTLA-4 nanobody improves the immunity of mice against challenges withStaphylococcus aureusandStreptococcus agalactiae
Authors: Wu Peng , Yang Ningning , Xu Mingguo , Chen Chuangfu
Published: March 2021

Cytotoxic T lymphocyte associated antigen 4 (CTLA-4), also known as CD152, is a transmembrane receptor and leukocyte differentiation antigen on T cells that participates in the negative regulation of immune responses. CTLA-4 Ig can effectively and specifically inhibit cellular and humoral immune responses in vivo and in vitro, and is therefore, considered to be a promising new immunosuppressive antibody. In this study, we investigated the role of CTLA-4 nanobody in immunity. We purified recombinant CTLA-4 protein and constructed a phage display nanobody library. After screening the library, we obtained a nanobody with high affinity for the CTLA-4 protein. The nanobody was expressed and purified and the specific high-affinity for CTLA-4 confirmed by enzyme-linked immunosorbent assay. The nanobody was shown to enhance the activity and nitric oxide (NO) production of bone marrow derived dendritic cells (DCs) as well as their ability to capture foot-and-mouth disease virus (FMDV). The CTLA-4 nanobody also improved the immunity of animals after challenge withStaphylococcus aureusandStreptococcus agalactiae, thus indicating the potential of the CTLA-4 nanobody to improve cellular immunity and enhance immune responses.
Post-embryonic development and aging of the appendicular skeleton inAmbystoma mexicanum
Authors: Riquelme-Guzmán Camilo , Schuez Maritta , Böhm Alexander , Knapp Dunja , Edwards-Jorquera Sandra , Ceccarelli Alberto S. , Chara Osvaldo , Rauner Martina , Sandoval-Guzmán Tatiana
Published: March 2021

Background

The axolotl is a key model to study appendicular regeneration. The limb complexity resembles that of humans in structure and tissue components; however, axolotl limbs develop post-embryonically. In this work, we evaluated the post-embryonic development of the appendicular skeleton and its changes with aging.

Results

The juvenile limb skeleton is formed mostly bySox9/Col1a2cartilage cells. Ossification of the appendicular skeleton starts when animals reach a length of 10 cm, and cartilage cells are replaced by a primary ossification center, consisting of cortical bone and an adipocyte-filled marrow cavity. Vascularization is associated with the ossification center and the marrow cavity formation. We identified the contribution ofCol1a2-descendants to bone and adipocytes. Moreover, ossification progresses with age towards the epiphyses of long bones. Axolotls are neotenic salamanders, and still ossification remains responsive to L-thyroxine, increasing the rate of bone formation.

Conclusions

In axolotls, bone maturation is a continuous process that extends throughout their life. Ossification of the appendicular bones is slow and continues until the complete element is ossified. The cellular components of the appendicular skeleton change accordingly during ossification, creating a heterogenous landscape in each element. The continuous maturation of the bone is accompanied by a continuous body growth.
Immune checkpoint inhibitors and cellular treatment for lymphoma immunotherapy
Authors: Li F , Chen Y , Pang M , Yang P , Jing H
Published: March 2021

Malignant lymphoma (ML) is a common hematological malignancy with many subtypes. Patients with ML usually undergo traditional treatment failure and become relapsed or refractory (R/R) cases. Recently, immunotherapy, such as immune checkpoint inhibitors (ICIs) and cellular treatment, has gradually emerged and used in clinical trials with encouraging achievements for ML treatment, which exerts anti-tumor activity by blocking the immune evasion of tumor cells and enhancing the attack ability of immune cells. Targets of immune checkpoints include programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3). Examples of cellular treatment are chimeric antigen receptor (CAR) T cells, cytokine-induced killer (CIK) cells and natural killer (NK) cells. This review aimed to present the current progress and future prospects of immunotherapy in lymphoma, with the focus upon ICIs and cellular treatment.
Evolution of a melanoma in situ to a sarcomatoid dedifferentiated melanoma
Authors: Chung Jina , Shevchenko Alina , Lee Jason B.
Published: March 2021

Sarcomatoid dedifferentiated melanoma (SDDM) is a recently recognized subtype of melanoma that stains diffusely for CD10 and lacks the expression of the usual melanocytic markers including S100, SOX10, MITF, and Melan A. Advances in next‐generation DNA sequencing technology have facilitated the increased recognition of this rare, aggressive spindle cell melanoma. Herein, a case of relatively early lesion of SDDM arising in association with melanoma in situ is highlighted. A 72‐year‐old man with a history of previously treated melanoma in situ on the face five years prior presented with a new rapidly growing lesion within the scar of the treated site. A shave biopsy of the lesion revealed a centrally located 1.8‐mm deep, poorly differentiated spindle cell neoplasm in association with an adjacent recurrent melanoma in situ. The spindle cell component stained diffusely for CD10, but failed to stain for S100, SOX10, and Melan‐A while the melanoma in situ expressed all three melanocytic markers. Next‐generation DNA sequencing assay revealed mutations in NF1, CDKN2A, TP53, and TSC1. A diagnosis of stage 2B SDDM arising in association with melanoma in situ was established based on the clinical context and genomic assay results.
How Buddhist beliefs relate to blood donation intention: The role of moral attentiveness and self‐monitoring
Authors: Chen Liangyong , Zhang Sai , Zhou Yufeng , Xiao Mo
Published: March 2021

Buddhism is prevalent in Asia and has been growing in Western countries. Its perspectives have subtle influences on people’s ways of thinking and behaving. This study focuses on the association between Buddhist beliefs and blood donation intention. We draw on a social‐cognitive perspective to delineate how this link is mediated by moral attentiveness and moderated by self‐monitoring. Data were collected via online surveys, and 508 respondents were included in the final sample. We used Hayes’ PROCESS macro and simple slope analysis to assess all relationships in our moderated mediation model. Results indicated that Buddhist beliefs were positively related to blood donation intention, and moral attentiveness mediated this relationship. Moreover, self‐monitoring was found to moderate the direct relationship between Buddhist beliefs and moral attentiveness, as well as the indirect relationship between Buddhist beliefs and blood donation intention through moral attentiveness. The associations were strengthened with increased self‐monitoring. This research provides a nuanced explanation of the manner in which Buddhist beliefs are associated with blood donation intention. Blood donation recruitment campaigns can incorporate instrumental elements of Buddhist teachings, such as the pursuit of moral perfection, the cultivation of the virtues of unselfishness, benevolence and understanding, and the laws of Karma. Meanwhile, mindfulness as a core practice in Buddhism can be utilized to improve moral attentiveness and self‐monitoring, thereby promoting blood donation intention.
Implication of TrkC‐miR2 in neurotrophin signalling pathway regulation through NGFR transcript targeting
Authors: Dokaneheifard Sadat , Soltani Bahram M.
Published: March 2021

TrkC and NGFR neurotrophin receptors are associated with cell death, cancer and differentiation. TrkC‐miR2, which is located in TrkC gene, is known to regulate Wnt signalling pathway, and its influence on other signalling pathways is under investigation. Here, through RT‐qPCR, dual‐luciferase assay and Western blotting we reveal that TrkC‐miR2 targets NGFR. Overexpression of TrkC‐miR2 also affected TrkA, TrkC, NFKB, BCL2 and Akt2 expressions involved in neurotrophin signalling pathway, and elevated survival rate of HEK293t and U87 cells was distinguished by flow cytometry and MTT assay. Consistently, an opposite expression correlation was obtained between TrkC‐miR2 and NGFR or TrkC for the duration of NT2 differentiation. Meanwhile, TrkC‐miR2 down‐regulation attenuated NT2 differentiation into neural‐like cells. Overall, here we present in silico and experimental evidence showing TrkC‐miR2 as a new controller in regulation of neurotrophin signalling pathway.