bluuebunny/crossref_metadata_2025 huggingface dataset:
Postacute Care Disposition for Total Hip and Total Knee Replacement Surgery for Asian Americans
Authors: Reynolds Grace L. , Fisher Dennis G.
Published: March 2020

This study explored differences in postacute disposition for total hip arthroplasty (THA) and total knee arthroplasty (TKA) with a focus on whether Asian Americans (AS) experience joint replacement disparities observed in other racial/ethnic minorities compared with majority white patients. We used data from the Nationwide Inpatient Sample for 2009 through 2012. We looked at disposition to home health care (HHC) and transfer to another facility for postacute care (e.g., skilled nursing facility, rehabilitation facility) for each of the 4 years under study. Findings for AS were mixed. There were differences in discharge to postacute facilities other than HHC for AS compared with whites for THA for 2011 and 2012. For TKA, there were differences in disposition to HHC for Asians compared with whites for 2009 and 2012; for disposition to postacute facilities other than HHC for TKA, there were differences for 2011 and 2012 only. Differences for AS in postacute disposition to facilities other than HHC appear to increase over the 4 years of the study. Further research with additional data is warranted.
Paternalistic aims and (mis)attributions of agency: What the over-punishment of Black girls in US classrooms teaches us about just school discipline
Authors: Lamboy Lily , Taylor Ashley , Thompson Winston
Published: March 2020

In this article, we explore the interrelated phenomena of teachers’ paternalistic aims and their misattributions of the agency of their students within particular schooling contexts of systemic racial injustice in the United States. We argue that, because teachers in these contexts assess agency in patterned, predictable ways that stem from – and reify – preexisting unjust patterns of oppression, teachers are unreliable evaluators of the conditions necessary for just punishment. To build this argument, we explore a complex case in which authorities regularly fail to meet these conditions: the punishment of Black girls in low-income, urban, predominantly non-White primary and secondary schools in the United States. Through our analysis, we offer a new concept, excess agency misattribution, which raises serious questions about subjective justifications for punishment in contexts of entrenched injustice. By delineating how the perceptions of teachers influence both the putative justifying aims and targeted recipients of punishment, we demonstrate how the existing terrain of school punishment practices ought to affect our normative reasoning about the fairness of punishment in these contexts.
Study of Indicators for Early and Rapid Diagnosis of Radiation Injury Is the Most Important in Patients With Cancer During Radiotherapy
Authors: Liu Gang , Niu Li-Mei , Wang Li-Qin , Li Ye , Wu Xiao-Qin , Liu Yin-Yin , Zhang Rong
Published: March 2020

Objective:

To establish a complete technical solution for the radiation biological dose estimation, to enable prediction of individuals’ response to radiotherapy (RT), and to control treatment dose for reduced irradiation injury and promote repair; and to evaluate the risk of radiation-induced late effects for patients undergoing external photon beam RT and provide the reliable dose–response relationships.

Methods:

Select 49 tumor patients using 60Co and linear accelerator for radiation therapy; initial radiation dose was 250 cGy. Chromosome aberration and blood count were analyzed before radiation therapy and 2 hours after the first day of RT.

Results:

Two hours after the first day of RT, peripheral blood cell count of lymphocytes of patients with cancer was significantly decreased ( P < .01). The frequency of chromosome aberration was higher ( P < .01).

Conclusion:

High-dose radiation of the radiation therapy makes significant injuries to peripheral blood lymphocytes.
Concussion knowledge and attitudes amongst community club rugby stakeholders
Authors: van Vuuren Hanno , Welman Karen , Kraak Wilbur
Published: March 2020

Due to the nature of rugby, concussions are a frequent occurrence and can go undetected by different stakeholders. Knowledge regarding identification of symptoms, management and prevention of re-injury is crucial for the welfare of players. The aim of the study was to determine the concussion knowledge and attitudes among different community club rugby stakeholders. The study gathered quantitative information by utilizing the Rosenbaum Concussion Knowledge and Attitude Survey-Student Version (RoCKAS-ST). Of all the participants (N = 434), medical staff (79 ± 10%) provided the highest Concussion Knowledge Index scores followed by referees (78 ± 8%) and players (67 ± 13%). The stakeholders scored 76% overall for Concussion Attitude Index. Across the scenarios the different participants believed to have safer attitudes compared to that of others within their team. Statistical differences were found between stakeholders when asked if concussion is less important than other injuries, as players, coaches and administrative staff all indicated an unsafe response in contrast to that of referees (p < 0.01). Players indicated an unsafe attitude towards returning to play, while symptomatic as a result of a concussion whereas coaches indicated a safer response (p < 0.01). Only two out of eight legitimate symptoms, headaches and dizziness, were correctly identified by 80% or more of participants, which warrants concern that identification of symptoms could be lacking on this level. Investigating the knowledge and attitudes of concussion at community club rugby level could identify which areas are to be further targeted by the South African Rugby Union.
Accuracy of combined quantitative diffusion-weighted MRI and routine contrast-enhanced MRI in discrimination of benign and malignant salivary gland tumors
Authors: Nada Ayman , Hady Dina , Youssef Ayda , Mahmoud Esmat , Assad Ramy Edward
Published: March 2020

Background

Preoperative imaging of salivary gland tumors is important for predicting and differentiating benign from malignant tumors, and for aiding management planning. We aimed to investigate the accuracy of combined quantitative diffusion-weighted magnetic resonance imaging (MRI) and routine contrast-enhanced MRI in the evaluation of salivary gland tumors and the differentiation of benign from malignant tumors.

Results

This study included 51 patients with a total of 16 benign and 35 malignant lesions that were detected by histopathological analysis. There was a statistically significant difference between the apparent diffusion coefficient values (ADC) of malignant and benign lesions (0.69 ± 0.22 × 10−3 mm2/s and 1.39 ± 0.52 × 10−3 mm2/s respectively). The optimal cut-off ADC value was 1.08 with 75% specificity and 97% sensitivity. The routine contrast-enhanced MRI had predicted benign and malignant tumors with 65% sensitivity and 44% specificity. The sensitivity and specificity were greatly increased when quantitative diffusion-weighted MRI was combined with routine contrast-enhanced MRI: 100%, and 88% respectively. A receiver operating curve was generated. The area under curve was 0.88 ( p < 0.001, 95% CI: 0.76–0.99).

Conclusion

Combined quantitative diffusion-weighted MRI with ADC measurements and routine contrast-enhanced magnetic resonance imaging are helpful tools for the evaluation of salivary gland tumors and help differentiate benign from malignant lesions.
Secondary prevention through comprehensive cardiovascular rehabilitation: From knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology
Authors: Ambrosetti Marco , Abreu Ana , Corrà Ugo , Davos Constantinos H , Hansen Dominique , Frederix Ines , Iliou Marie C , Pedretti Roberto F E , Schmid Jean-Paul , Vigorito Carlo , Voller Heinz , Wilhelm Matthias , Piepoli Massimo F , Bjarnason-Wehrens Birna , Berger Thomas , Cohen-Solal Alain , Cornelissen Veronique , Dendale Paul , Doehner Wolfram , Gaita Dan , Gevaert Andreas B , Kemps Hareld , Kraenkel Nicolle , Laukkanen Jari , Mendes Miguel , Niebauer Josef , Simonenko Maria , Zwisler Ann-Dorthe Olsen
Published: March 2020

Secondary prevention through comprehensive cardiac rehabilitation has been recognized as the most cost-effective intervention to ensure favourable outcomes across a wide spectrum of cardiovascular disease, reducing cardiovascular mortality, morbidity and disability, and to increase quality of life. The delivery of a comprehensive and ‘modern’ cardiac rehabilitation programme is mandatory both in the residential and the out-patient setting to ensure expected outcomes. The present position paper aims to update the practical recommendations on the core components and goals of cardiac rehabilitation intervention in different cardiovascular conditions, in order to assist the whole cardiac rehabilitation staff in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and patients in the recognition of the positive nature of cardiac rehabilitation. Starting from the previous position paper published in 2010, this updated document maintains a disease-oriented approach, presenting both well-established and more controversial aspects. Particularly for implementation of the exercise programme, advances in different training modalities were added and new challenging populations were considered. A general table applicable to all cardiovascular conditions and specific tables for each clinical condition have been created for routine practice.
Percentages of problem drug use and their implications for policy making: A review of the literature
Authors: Schlag Anne Katrin
Published: March 2020

This paper reviews the literature on problem drug use, aiming to answer the question ‘what percentages of drug users are problem drug users?’ We look at the conceptualisation of problem drug use, and related concepts such as addiction and dependence. While conceptually distinct, definitions vary, and terms are often utilised interchangeably in the literature. Because of the heightened controversy and recurring moral panics (often without factual basis) related to illicit drugs as compared to the licit drugs, we focus primarily on the use of the former. We summarise previous research findings on percentages of problem drug user in general as well as for the most commonly used illicit substances more specifically. Results show that the majority of drug use is episodic, transient and generally non-problematic. The majority of people who have used various drugs in their lifetime have not done so in the past year. Only a minority become problem drug users. Appreciating the limitations of current research, further research avenues are outlined and implications for policy making are provided. If most drug use is indeed non-problematic it implies the need for policy changes with a heightened focus on the development of improved risk communications and other harm reduction strategies. There is a need to move away from the narrative of ‘the problem drug user’ which is in many ways still prevalent in informing policy making. Incorrect perceptions of drugs and people who use drugs should be countered by providing evidence-based, transparent and easily accessible information. This is essential to change public attitudes towards and remove stigma of people who use drugs.
Exploring feature selection and classification methods for predicting heart disease
Authors: Spencer Robinson , Thabtah Fadi , Abdelhamid Neda , Thompson Michael
Published: March 2020

Machine learning has been used successfully to improve the accuracy of computer-aided diagnosis systems. This paper experimentally assesses the performance of models derived by machine learning techniques by using relevant features chosen by various feature-selection methods. Four commonly used heart disease datasets have been evaluated using principal component analysis, Chi squared testing, ReliefF and symmetrical uncertainty to create distinctive feature sets. Then, a variety of classification algorithms have been used to create models that are then compared to seek the optimal features combinations, to improve the correct prediction of heart conditions. We found the benefits of using feature selection vary depending on the machine learning technique used for the heart datasets we consider. However, the best model we created used a combination of Chi-squared feature selection with the BayesNet algorithm and achieved an accuracy of 85.00% on the considered datasets.
Ideal implant choice for proximal interphalangeal joint arthrodesis in hammer toe/claw toe deformity correction: A systematic review
Authors: Wei Rachel XY , Ling Samuel KK , Lui TH , Yung Patrick SH
Published: March 2020

Intramedullary devices have been developed to reduce the problems associated with Kirschner (K)-wire fixation in proximal interphalangeal joint (PIPJ) arthrodesis. The purpose of this systematic review is to compare the surgical outcomes of K-wires versus novel internal fixation devices in PIPJ arthrodesis in claw/hammer toe surgery. The databases searched were PubMed, Scopus, Cochrane, and Embase with keywords “claw toe OR hammer toe” AND “proximal interphalangeal OR PIP” AND “fusion OR arthrodesis.” Clinical trials published in English with evidence levels I, II, and III were included. Five studies, including one randomized controlled trial and four case-controlled studies, were identified to meet the inclusion criteria. Overall, the studies showed promising results in union rates using the novel internal devices compared to K-wires. However, the novel internal devices seem not to present advantages in clinical parameters such as pain levels, patient satisfaction, foot-related function, or surgical complication rates.
Extensor hallucis longus tendon is a new distal landmark for coronal tibial component alignment in total knee arthroplasty: A study of magnetic resonance imaging
Authors: Hino Manabu , Nakagawa Shuji , Arai Yuji , Inoue Hiroaki , Kan Hiroyuki , Fujii Yuta , Ikoma Kazuya , Kubo Toshikazu
Published: March 2020

Purpose:

In total knee arthroplasty (TKA), various landmarks are generally used to ensure correct osteotomy. In this study, we examined whether the tibialis anterior tendon (TAT) or the extensor hallucis longus tendon (EHLT) could be used as a landmark of the center of the ankle joint in patients with knee osteoarthrosis (OA), using magnetic resonance imaging (MRI).

Methods:

The subjects were 61 patients with OA in 79 knees (males: 8 with 9 knees and females: 53 with 70 knees). With the ankle joint secured in the intermediate position, MRI from the knee joint to the ankle joint was performed in the same foot position. We prepared individual lines connecting the center of the ankle joint with the TAT or EHLT to measure the angle difference (ΔA) from Akagi’s line in the knee joint. We analyzed whether the ΔA might be affected by deformity of the knee joint or foot region, and tibial torsion.

Results:

At the ankle joint level, the ΔA of EHLT was the smallest, with an average of 1.6 ± 3.4°. The ΔA for the femorotibial angle, hallux valgus angle, and varus–valgus angle showed no correlations with deformity of the knee joint and foot region, or tibial torsion.

Conclusions:

MRI findings showed that EHLT would be useful as a landmark of the ankle joint center in extramedullary tibial osteotomy in TKA for medial knee OA. It was also clarified that the landmark would not be affected by severe deformity of the knee joint, deformity of the foot region, or external torsion of the tibia.
Proximal Over-resection During Femoral Osteochondroplasty Negatively Affects The Distractive Stability Of The Hip Joint
Authors: Lazaro Lionel E. , Lim Daniel P. , Nelson Trevor , Eberlein Samuel , Banffy Michael B. , Metzger Melodie
Published: March 2020

Objectives:

Hip microinstability is an increasingly recognized source of hip pain and disability. Femoral osteochondroplasty is usually performed with direct visualization through an arthroscope, assisted with repeated fluoroscopic imaging. However, a two-dimensional representation of a three-dimensional structure is misleading and may compromise the precision of the planned osteochondroplasty. The resection can occasionally extend proximally into the Femoral Head diminishing the articular surface area available for suction seal. The purpose of this study was to determine whether proximal over-resection decreases the rotational and distractive stability of the hip joint.

Methods:

Six hemi-pelvises were repeatedly tested in the following conditions: (a) intact, (b) T-capsulotomy, (c) Osteochondroplasty to the physeal scar, followed by (d) 5mm and (e) 10mm proximal extension. The pelvis was secured to a metal plate and the femur was potted and attached to a multi-axial hip jig. Specimens were axially distracted with a load from 0-150N followed by 5Nm of internal and external torque at 0o, 15o, 30o, 60o, 90o of flexion. Displacement/rotation was recorded using a 3D motion tracking system. Repeated measures ANOVA was used with significance set at p<0.05.

Results:

Proximal extension of the resection by 5mm and 10mm increased axial instability at every angle of flexion tested, with the greatest increase observed at higher angles of flexion,p<0.05. T-capsulotomy alone increased both internal and external rotation at all angles of flexion, p<0.05. Subsequent resection and extension of the resection did not significantly increase rotational instability compared to the capsulotomy state.

Conclusion:

Extending the osteochondroplasty proximally into the femoral head compromises the distractive stability of the hip joint, but doesn’t not effect hip rotational stability. Clinically, this highlights the importance of accuracy when performing femoral osteochondroplasty to minimize proximal extension that may increase iatrogenic instability of the hip joint, leading to reduced post-operative outcomes.
An Update on Foot and Ankle Fellowship Website Content and Accessibility
Authors: Khwaja Ansab , Du Peter , Sherman Nathan , Truchan Lisa
Published: March 2020

Background:

The content and accessibility of foot and ankle fellowship websites impact applicants and fellowship programs. This study aimed to evaluate the accessibility provided via the American Orthopaedic Foot & Ankle Society (AOFAS) websites and individual websites.

Methods:

The AOFAS website was used to identify existing foot and ankle fellowship programs. The database information was reviewed for links to fellowship program websites, which was corroborated through a Google search for accessibility. Information from fellowship program websites and the AOFAS was analyzed for the presence of recruitment and educational content, and this analysis was compared to previously reported metrics.

Results:

Forty-eight orthopedic foot and ankle fellowship programs were identified. The AOFAS database featured direct links to 19 (40%) fellowship websites with the Google search providing direct links to 35 (73%) websites. Foot and ankle fellowship information markedly improved in domains of Salary/Benefits (+233%), Rotations/Curriculum (+199%), and Faculty Listing (+67%), but there was a reduction in available content in the domains of Operative Experience (–79%), Office/Clinic information (–78%), and Didactics (–39%) compared with the lone existing study.

Conclusion:

There continues to be variability between foot and ankle fellowship websites and the AOFAS website regarding program content and descriptions. Some information is more readily available, but other domains have less information now than in previously reported research.
Overcoming COVID-19: What can human factors and ergonomics offer?
Authors: Gurses Ayse P , Tschudy Megan M , McGrath-Morrow Sharon , Husain Amyna , Solomon Barry S , Gerohristodoulos Kylee A , Kim Julia M
Published: March 2020

A novel coronavirus disease, named coronavirus disease 2019 or COVID-19, which sparked an outbreak in Wuhan, China in December 2019, is now a pandemic. The rapid spread of this disease from one to more than 155 regions worldwide in 2.5 months highlights the need for better preparation to manage a pandemic. In this commentary, we describe how Human Factors and Ergonomics (HFE) can contribute to the COVID-19 pandemic response. Specifically, we provide an example of how HFE methodologies informed workflow redesigns implemented as part of COVID-19 pandemic preparations in an academic pediatric ambulatory clinic. We then identify key mechanisms and areas where HFE can contribute to and improve the effectiveness of a pandemic response: Just-in-time (JIT) training development, adapting workflows and processes, restructuring teams and tasks, developing effective mechanisms and tools for communication, engaging patient and families to follow the recommended practices (e.g., social distancing, revised hospital visitation policies), identifying and mitigating barriers to implementation of plans, and learning from failures and successes to improve both the current and future pandemic responses. We recommend integrating HFE approaches and tools across health care systems, state health organizations, and the Centers for Disease Control and Prevention (CDC) as they confront this pandemic.
Several Notes on the Existential Hermeneutic Phenomenology for Project Management and Possibilities of Its Extension by Other Existential Concepts: Case Study From the Research Project Team
Authors: Müller Michal , Jedličková Lenka
Published: March 2020

In this article, we follow up the approach of employing existential hermeneutic phenomenology (EHP) (Rolfe et al., 2016) published in Project Management Journal® and we show that this innovative method, useful in managerial self-development, represents an important tool for learning not only in the private sector, but also in public research projects where managerial skills are required. In this article, we propose an extended EHP framework that includes the original ideas of phenomenologists Fink and Patočka. We present the results of our interpretative phenomenological analysis study, where issues of communication and interpersonal relationships emerge as key problems in project work.
A murine photothrombotic stroke model with an increased fibrin content and improved responses to tPA-lytic treatment
Authors: Sun Yu-Yo , Kuo Yi-Min , Chen Hong-Ru , Short-Miller Jonah C. , Smucker Marchelle R. , Kuan Chia-Yi
Published: March 2020

The Rose Bengal (RB) dye-based photothrombotic stroke (PTS) model has many methodological advantages including consistent location and size of infarct, low mortality, and relatively simple surgical procedures. However, the standard PTS has the caveat of poor responses to tissue-type plasminogen activator (tPA)–mediated lytic treatment, likely as a result of the platelet-rich, fibrin-poor content of the blood clots. Here we tested whether the admixture of thrombin (80 U/kg) and RB dye (50 mg/kg) in the proximal middle cerebral artery (MCA)–targeted PTS will modify the clot composition and elevate the responsiveness to tPA-lytic treatment (Alteplase, 10 mg/kg). Indeed, intravital imaging, immunostaining, and immunoblot analyses showed less-compacted platelet aggregates with a higher fibrin content in the modified thrombin (T) plus RB photothrombotic stroke (T+RB-PTS) model compared with the standard RB-PTS-induced clots. Both RB-PTS and T+RB-PTS showed steady recovery of cerebral blood flow (CBF) in the ischemic border from 1 day after infarction, but without recanalization of the proximal MCA branch. Intravital imaging showed high potency of restoring the blood flow by tPA after single vessel-targeted T+RB-PTS. Further, although intravenous tPA failed to restore CBF or attenuate infarction in RB-PTS, it conferred 25% recovery of CBF and 55% reduction of the infarct size in T+RB-PTS (P < .05) if tPA was administered within 2 hours postphotoactivation. These results suggest that T+RB-PTS produces mixed platelet:fibrin clots closer to the clinical thrombus composition and enhanced the sensitivity to tPA-lytic treatment. As such, the modified photothrombosis may be a useful tool to develop more effective thrombolytic therapies of cerebral ischemia.
Checkpoint inhibition before haploidentical transplantation with posttransplant cyclophosphamide in Hodgkin lymphoma
Authors: De Philippis Chiara , Legrand-Izadifar Faezeh , Bramanti Stefania , Giordano Laura , Montes de Oca Catalina , Duléry Rémy , Bouabdallah Reda , Granata Angela , Devillier Raynier , Mariotti Jacopo , Sarina Barbara , Harbi Samia , Maisano Valerio , Furst Sabine , Pagliardini Thomas , Weiller Pierre-Jean , Lemarie Claude , Calmels Boris , Chabannon Christian , Santoro Armando , Mohty Mohamad , Blaise Didier , Castagna Luca
Published: March 2020

We report on 59 Hodgkin lymphoma patients undergoing haploidentical stem cell transplantation (SCT; haplo-SCT) with posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis, comparing outcomes based on pretransplant exposure to checkpoint inhibitors (CPIs). Considering pretransplant characteristics, the 2 cohorts (CPI = 29 patients vs no-CPI = 30 patients) were similar, except for the number of prior lines of therapy (6 vs 4; P < .001). With a median follow-up of 26 months (range, 7.5-55 months), by univariate analysis, the 100-day cumulative incidence of grade 2-4 acute GVHD was 41% in the CPI group vs 33% in the no-CPI group (P = .456), whereas the 1-year cumulative incidence of moderate to severe chronic GVHD was 7% vs 8%, respectively (P = .673). In the CPI cohort, the 2-year cumulative incidence of relapse appeared lower compared with the no-CPI cohort (0 vs 20%; P = .054). No differences were observed in terms of overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) (at 2 years, 77% vs 71% [P = .599], 78% vs 53% [P = .066], and 15% vs 21% [P = .578], respectively). By multivariable analysis, CPI before SCT was an independent protective factor for PFS (hazard ratio [HR], 0.32; P = .037). Stable disease (SD)/progressive disease (PD) was an independent negative prognostic factor for both OS and PFS (HR, 14.3; P < .001 and HR, 14.1; P < .001, respectively) . In conclusion, CPI as a bridge to haplo-SCT seems to improve PFS, with no impact on toxicity profile.
Late infectious complications in hematopoietic cell transplantation survivors: a population-based study
Authors: Foord Aimee M. , Cushing-Haugen Kara L. , Boeckh Michael J. , Carpenter Paul A. , Flowers Mary E. D. , Lee Stephanie J. , Leisenring Wendy M. , Mueller Beth A. , Hill Joshua A. , Chow Eric J.
Published: March 2020

Few studies have compared the incidence of infections occurring ≥2 years after hematopoietic cell transplant (HCT) with other cancer patients and the general population. In this study, ≥2-year HCT survivors who were Washington residents treated from 1992 through 2009 (n = 1792; median age, 46 years; 52% allogeneic; 90% hematologic malignancies) were matched to individuals from the state cancer registry (n = 5455, non-HCT) and driver’s license files (n = 16 340; Department of Licensing [DOL]). Based on hospital and death registry codes, incidence rate ratios (IRRs; 95% confidence interval [CI]) of infections by organism type and organ system were estimated using Poisson regression. With 7-year median follow-up, the incidence rate (per 1000 person-years) of all infections was 65.4 for HCT survivors vs 39.6 for the non-HCT group (IRR, 1.6; 95% CI, 1.3-1.9) and 7.2 for DOL (IRR, 10.0; 95% CI, 8.3-12.1). Bacterial and fungal infections were each 70% more common in HCT vs non-HCT cancer survivors (IRR, 1.7; P < .01), whereas the risk for viral infection was lower (IRR, 1.4; P = .07). Among potentially vaccine-preventable organisms, the IRR was 3.0 (95% CI, 2.1-4.3) vs the non-HCT group. Although the incidences of all infections decreased with time, the relative risk in almost all categories remained significantly increased in ≥5-year HCT survivors vs other groups. Risk factors for late infection included history of relapse and for some infections, history of chronic graft-versus-host disease. Providers caring for HCT survivors should maintain vigilance for infections and ensure adherence to antimicrobial prophylaxis and vaccination guidelines.
Designing Aptamer-Gold Nanoparticle-Loaded pH-Sensitive Liposomes Encapsulate Morin for Treating Cancer
Authors: Ding Xiaoyuan , Yin Chenyang , Zhang Weiwei , Sun Yu , Zhang Zhenzhen , Yang Endong , Sun Dongdong , Wang Weiyun
Published: March 2020

This study proposes the synthesis of a type of anticancer nanoparticle, aptamers and Au nanoparticle (Apt-Au)-modified Morin pH-sensitive liposome (MSL), which exhibits targeting properties. Tumors are difficult to cure because their microenvironment varies from that of normal tissue; its pH is lower than that of normal tissue, which generally impedes the effectiveness of drugs. Thus, pH-responsive drugs have attracted extensive attention. Gold nanoparticles (AuNPs) show potential as drug carriers because of their small size, good biocompatibility, easy surface modification, and strong cell penetration. Apt-Au@MSL exhibits excellent monodispersity and tumor-targeting properties and can be released in partly acidic environment via dialysis. We screened our model cancer cell by MTT assay and found that SGC-7901 cells can effectively suppress proliferation. In vivo results demonstrate that the administration of Apt-Au@MSL could inhibit tumor growth in xenograft mouse models. H&E staining and TUNEL assay further confirmed that Apt-Au@MSL can promote tumor apoptosis. Apt-Au@MSL may induce apoptosis by triggering overproduction of reactive oxygen species (ROS) and regulating multiple signal crosstalk. Both blood biochemistry tests and H&E staining suggested that these materials exhibit negligible acute toxicity and good biocompatibility in vivo. With its powerful function, Apt-Au@MSL can be used as a target-based anticancer material for future clinical cancer treatment.
OsVPE3 Mediates GA-induced Programmed Cell Death in Rice Aleurone Layers via Interacting with Actin Microfilaments
Authors: Zhang Heting , Xiao Yu , Deng Xiaojiang , Feng Hongyu , Li Zhe , Zhang Lulu , Chen Huiping
Published: March 2020

Background

Vacuolar processing enzymes (VPEs) have been identified as the enzymes that regulate vacuole-mediated programmed cell death (PCD) in plants. The mechanism that VPE regulates the PCD in rice aleurone layers remains unknown.

Results

The aleurone layers treated with distilled water exerted caspase-1 and VPE activity, both of which were inhibited by the caspase-1 specific inhibitor Ac-YVAD-CMK but not by the caspase-3 specific inhibitor Ac-DEVD-CHO. However, the caspase-1 and caspase-3 inhibitors weakened the activity of caspase-3. Combined with the effects of endogenous gibberellin (GA) on the induction of OsVPEs, we suggest that the OsVPE3 in the aleurone layers, which exhibits caspase-1-like activity, is a key molecule in GA-induced PCD via regulating the protease with caspase-3-like activity. Many studies have confirmed that vacuolar fusion is an important feature of vacuole-mediated PCD in plants. In this experiment, the process of vacuole fusion was accompanied by changes in the structure of actin filaments (AFs), specifically, their depolymerization and polymerization. The process of vacuolar fusion was accelerated or delayed by the promotion or inhibition of the depolymerization of AFs, respectively. Here, the inhibition of OsVPE3 blocked the depolymerization of AFs and delayed the fusion of vacuoles, indicating that OsVPE3 can regulate the fusion of vacuoles in rice aleurone layers via mediating AFs. Furthermore, the depolymerization of AFs contributed to the up-regulation of OsVPE3 gene expression and VPE activity, resulting in accelerated PCD in rice aleurone layers. However, the inhibitor of VPE reversed the effects of AF depolymerization on the activity of VPE, then postponing the process of PCD, implying that AF can involve in GA-induced PCD of rice aleurone layers by mediating OsVPE3.

Conclusions

Together, activation of OsVPE3 and depolymerization of AFs shortened the process of vacuolation and PCD in rice aleurone layers, and OsVPE3 interacted with AFs during regulation.
Bacterial chemotaxis: a way forward to aromatic compounds biodegradation
Authors: Ahmad Fiaz , Zhu Daochen , Sun Jianzhong
Published: March 2020

Worldwide industrial development has released hazardous polycyclic aromatic compounds into the environment. These pollutants need to be removed to improve the quality of the environment. Chemotaxis mechanism has increased the bioavailability of these hydrophobic compounds to microorganisms. The mechanism, however, is poorly understood at the ligand and chemoreceptor interface. Literature is unable to furnish a compiled review of already published data on up-to-date research on molecular aspects of chemotaxis mechanism, ligand and receptor-binding mechanism, and downstream signaling machinery. Moreover, chemotaxis-linked biodegradation of aromatic compounds is required to understand the chemotaxis role in biodegradation better. To fill this knowledge gap, the current review is an attempt to cover PAHs occurrence, chemical composition, and potential posed risks to humankind. The review will cover the aspects of microbial signaling mechanism, the structural diversity of methyl-accepting chemotaxis proteins at the molecular level, discuss chemotaxis mechanism role in biodegradation of aromatic compounds in model bacterial genera, and finally conclude with the potential of bacterial chemotaxis for aromatics biodegradation.
Preferential drug delivery to tumor cells than normal cells using a tunable niosome–chitosan double package nanodelivery system: a novel in vitro model
Authors: Wiranowska Marzenna , Singh Rupin , Falahat Rana , Williams Eva , Johnson Joseph O. , Alcantar Norma
Published: March 2020

Background

We previously described the properties of a targeted drug delivery system (DDS) in a cell-free system. Here, in this comparative cell-based study (normal and tumor cells), we provide a quantitative analysis of the extracellular diffusion and intracellular localization of this DDS. This DDS consists of fluorescence-labeled paclitaxel encapsulated in non-ionic surfactant vesicles/niosomes embedded in a thermo-sensitive cross-linked chitosan hydrogel with an affinity for the MUC1 mucin surface antigen overexpressed on tumor cells, and designed for a sustained and controlled, localized delivery of embedded drugs. We evaluated DDS in our novel in vitro model using MatTek’ glass-bottom culture plates and compared human cancer cell lines (OV2008 epithelial origin carcinoma and U373 glioma, both overexpressing MUC1) with human normal epithelial control cell lines (IMMC3 and IOSE-121 using differential contrast and confocal microscopy.

Results

Tumor cells incubated in the presence of chitosan alone or DDS-containing chitosan–niosome–paclitaxel–BODIPY 564/570, showed a prominent granular accumulation on their surface when compared to the normal cells. Quantitation of gray value light intensity of the extracellular region of chitosan alone treated OV2008 and IOSE-121 controls done by analysis of multiple radial line segments, 4 µm each, using ImageJ software showed 2 times higher intensity around the OV2008 than around normal IOSE-121 controls (p < 0.05). In the DDS-treated OV2008 cells, extracellular fluorescence intensity measured at different diffusion distances outside of the cells, in three different zones showed the difference in means of fluorescence intensity in these zones (p < 0.05) with the highest level of fluorescence near the cell surface indicating a concentration gradient, most likely driven by the high affinity of chitosan to the MUC1 receptor. Also, as chitosan alone accumulated two times more along the edge of tumor cells compared to normal cells, we found intracellular fluorescence intensity quantified at time intervals to be also 2 times higher in OV2008 than in normal IMCC3 cells (p < 0.05).

Conclusion

Based on the observation of the DDS preferentially targeting tumor cells, there is a potential implication for the localized delivery of therapeutic drug doses to solid tumors or post-surgical solid tumors cavities containing residual tumor cells.
LncRNA MALAT1 exhibits positive effects on nucleus pulposus cell biology in vivo and in vitro by sponging miR-503
Authors: Zheng Hongyu , Wang Tingting , Li Xiangmin , He Wei , Gong Zhiqiang , Lou Zhenkai , Wang Bing , Li Xingguo
Published: March 2020

Background

Intervertebral disc degeneration (IDD) is characterized by the loss of nucleus pulposus cells (NPCs) and phenotypic abnormalities. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are involved in the pathogenesis of IDD. In this study, we aimed to investigate the functional effects of lncRNA MALAT1 on NPCs in IDD and the possible mechanism governing these effects.

Results

We validated the decreased expression of MALAT1 in the IDD tissues, which was associated with decreased Collagen II and Aggrecan expression. In vitro,overexpressed MALAT1 could attenuate the effect of IL-1β on NPC proliferation, apoptosis, and Aggrecan degradation. In vivo,MALAT1 overexpression attenuated the severity of disc degeneration in IDD model rats. Our molecular study further demonstrated that MALAT1 could sponge miR-503, modulate the expression of miR-503, and activate downstream MAPK signaling pathways. The effects of MALAT1 on NPCs were partially reversed/aggregated by miR-503 mimics/inhibitor treatment.

Conclusion

Our data suggested that the MALAT1-miR-503-MAPK pathway plays a critical role in NPCs, which may be a potential strategy for alleviating IDD.
The effect of antibiotics on the gut microbiome: a metagenomics analysis of microbial shift and gut antibiotic resistance in antibiotic treated mice
Authors: Xu Lei , Surathu Anil , Raplee Isaac , Chockalingam Ashok , Stewart Sharron , Walker Lacey , Sacks Leonard , Patel Vikram , Li Zhihua , Rouse Rodney
Published: March 2020

Background

Emergence of antibiotic resistance is a global public health concern. The relationships between antibiotic use, the gut community composition, normal physiology and metabolism, and individual and public health are still being defined. Shifts in composition of bacteria, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) after antibiotic treatment are not well-understood.

Methods

This project used next-generation sequencing, custom-built metagenomics pipeline and differential abundance analysis to study the effect of antibiotic monotherapy on resistome and taxonomic composition in the gut of Balb/c mice infected with E. coli via transurethral catheterization to investigate the evolution and emergence of antibiotic resistance.

Results

There is a longitudinal decrease of gut microbiota diversity after antibiotic treatment. Various ARGs are enriched within the gut microbiota despite an overall reduction of the diversity and total amount of bacteria after antibiotic treatment. Sometimes treatment with a specific class of antibiotics selected for ARGs that resist antibiotics of a completely different class (e.g. treatment of ciprofloxacin or fosfomycin selected for cepA that resists ampicillin). Relative abundance of some MGEs increased substantially after antibiotic treatment (e.g. transposases in the ciprofloxacin group).

Conclusions

Antibiotic treatment caused a remarkable reduction in diversity of gut bacterial microbiota but enrichment of certain types of ARGs and MGEs. These results demonstrate an emergence of cross-resistance as well as a profound change in the gut resistome following oral treatment of antibiotics.
The genome-wide landscape of C:G > T:A polymorphism at the CpG contexts in the human population
Authors: Youk Jeonghwan , An Yohan , Park Seongyeol , Lee June-Koo , Ju Young Seok
Published: March 2020

Background

The C:G > T:A substitution at the CpG dinucleotide contexts is the most frequent substitution type in genome evolution. The mutational process is obviously ongoing in the human germline; however, its impact on common and rare genomic polymorphisms has not been comprehensively investigated yet. Here we observed the landscape and dynamics of C:G > T:A substitutions from population-scale human genome sequencing datasets including ~ 4300 whole-genomes from the 1000 Genomes and the pan-cancer analysis of whole genomes (PCAWG) Project and ~ 60,000 whole-exomes from the Exome Aggregation Consortium (ExAC) database.

Results

Of the 28,084,558 CpG sites in the human reference genome, 26.0% show C:G > T:A substitution in the dataset. Remarkably, CpGs in CpG islands (CGIs) have a much lower frequency of such mutations (5.6%). Interestingly, the mutation frequency of CGIs is not uniform with a significantly higher C:G > T:A substitution rate for intragenic CGIs compared to other types. For non-CGI CpGs, the mutation rate was positively correlated with the distance from the nearest CGI up to 2 kb. Finally, we found the impact of negative selection for coding CpG mutations resulting in amino acid change.

Conclusions

This study provides the first unbiased rate of C:G > T:A substitution at the CpG dinucleotide contexts, using population-scale human genome sequencing data. Our findings provide insights into the dynamics of the mutation acquisition in the human genome.
Identification, evolution and expression analyses of whole genome-wide TLP gene family in Brassica napus
Authors: Wang Tong , Hu Jingjing , Ma Xiao , Li Chunjin , Yang Qihang , Feng Shuyan , Li Miaomiao , Li Nan , Song Xiaoming
Published: March 2020

Background

Brassicais a very important genus of Brassicaceae, including many important oils, vegetables, forage crops, and ornamental horticultural plants.TLPfamily genes play important regulatory roles in the growth and development of plants. Therefore, this study used a bioinformatics approach to conduct the systematic comparative genomics analysis ofTLPgene family inB. napusand other three important Brassicaceae crops.

Results

Here, we identified a total of 29TLPgenes fromB. napusgenome, and they distributed on 16 chromosomes ofB. napus.The evolutionary relationship showed that these genes could be divided into six groups from Group A to F. We found that the gene corresponding toArabidopsis thaliana AT1G43640was completely lost inB. rapa,B. oleraceaandB. napusafter whole genome triplication. The gene corresponding toAT1G25280was retained in all the three species we analysed, belonging to 1:3:6 ratios. Our analyses suggested that there was a selective loss of some genes that might be redundant after genome duplication. This study proposed that theTLPgenes inB. napusdid not directly expansion compared with its diploid parentsB. rapa, andB. oleracea. Instead, an indirect expansion ofTLPgene family occurred in its two diploid parents. In addition, the study further utilized RNA-seq to detect the expression pattern ofTLPgenes between different tissues and two subgenomes.

Conclusions

This study systematically conducted the comparative analyses ofTLPgene family inB. napus, discussed the loss and expansion of genes after genome duplication. It provided rich gene resources for exploring the molecular mechanism ofTLPgene family. Meanwhile, it provided guidance and reference for the research of other gene families inB. napus.
Characterising the mechanisms underlying genetic resistance to amoebic gill disease in Atlantic salmon using RNA sequencing
Authors: Robledo Diego , Hamilton Alastair , Gutiérrez Alejandro P. , Bron James E. , Houston Ross D.
Published: March 2020

Background

Gill health is one of the main concerns for Atlantic salmon aquaculture, and Amoebic Gill Disease (AGD), attributable to infection by the amoebaNeoparamoeba perurans,is a frequent cause of morbidity. In the absence of preventive measures, increasing genetic resistance of salmon to AGD via selective breeding can reduce the incidence of the disease and mitigate gill damage. Understanding the mechanisms leading to AGD resistance and the underlying causative genomic features can aid in this effort, while also providing critical information for the development of other control strategies. AGD resistance is considered to be moderately heritable, and several putative QTL have been identified. The aim of the current study was to improve understanding of the mechanisms underlying AGD resistance, and to identify putative causative genomic factors underlying the QTL. To achieve this, RNA was extracted from the gill and head kidney of AGD resistant and susceptible animals following a challenge withN. perurans, and sequenced.

Results

Comparison between resistant and susceptible animals primarily highlighted differences mainly in the local immune response in the gill, involving red blood cell genes and genes related to immune function and cell adhesion. Differentially expressed immune genes pointed to a contrast in Th2 and Th17 responses, which is consistent with the increased heritability observed after successive challenges with the amoeba. Five QTL-region candidate genes showed differential expression, including a gene connected to interferon responses (GVINP1), a gene involved in systemic inflammation (MAP4K4), and a positive regulator of apoptosis (TRIM39). Analyses of allele-specific expression highlighted a gene in the QTL region on chromosome 17, cellular repressor of E1A-stimulated genes 1 (CREG1), showing allelic differential expression suggestive of a cis-acting regulatory variant.

Conclusions

In summary, this study provides new insights into the mechanisms of resistance to AGD in Atlantic salmon, and highlights candidate genes for further functional studies that can further elucidate the genomic mechanisms leading to resistance and contribute to enhancing salmon health via improved genomic selection.
The stringent response regulator (p) ppGpp mediates virulence gene expression and survival in Erwinia amylovora
Authors: Yang Ho-wen , Yu Menghao , Lee Jae Hoon , Chatnaparat Tiyakhon , Zhao Youfu
Published: March 2020

Background

The nucleotide second messengers, i.e., guanosine tetraphosphate and pentaphosphate [collectively referred to as (p) ppGpp], trigger the stringent response under nutrient starvation conditions and play an essential role in virulence in the fire blight pathogen Erwinia amylovora. Here, we present transcriptomic analyses to uncover the overall effect of (p) ppGpp-mediated stringent response in E. amylovora in the hrp-inducing minimal medium (HMM).

Results

In this study, we investigated the transcriptomic changes of the (p) ppGpp0 mutant under the type III secretion system (T3SS)-inducing condition using RNA-seq. A total of 1314 differentially expressed genes (DEGs) was uncovered, representing more than one third (36.8%) of all genes in the E. amylovora genome. Compared to the wild-type, the (p) ppGpp0 mutant showed down-regulation of genes involved in peptide ATP-binding cassette (ABC) transporters and virulence-related processes, including type III secretion system (T3SS), biofilm, and motility. Interestingly, in contrast to previous reports, the (p) ppGpp0 mutant showed up-regulation of amino acid biosynthesis genes, suggesting that it might be due to that these amino acid biosynthesis genes are indirectly regulated by (p) ppGpp in E. amylovora or represent specific culturing condition used. Furthermore, the (p) ppGpp0 mutant exhibited up-regulation of genes involved in translation, SOS response, DNA replication, chromosome segregation, as well as biosynthesis of nucleotide, fatty acid and lipid.

Conclusion

These findings suggested that in HMM environment, E. amylovora might use (p) ppGpp as a signal to activate virulence gene expression, and simultaneously mediate the balance between virulence and survival by negatively regulating DNA replication, translation, cell division, as well as biosynthesis of nucleotide, amino acid, fatty acid, and lipid. Therefore, (p) ppGpp could be a promising target for developing novel control measures to fight against this devastating disease of apples and pears.