bluuebunny/crossref_metadata_2025 huggingface dataset:
Deadband feedback-based scheduling approach for networked control system with variable sampling period
Authors: Tian Zhongda
Published: January 2021

Reasonable information scheduling strategies in the networked control system (NCS) can improve the quality of service of the network, reduce the conflict of information transmission in the network, and improve the overall performance of the NCS. In order to improve the performance of the NCS, a deadband feedback-based scheduling approach for the NCS with a variable sampling period is proposed. For the NCS with multi control loops, considering the limitation of network bandwidth resources, the dynamic real-time adjustment of a multi-loop sampling period is achieved through network utilization prediction, network bandwidth configuration and sampling period calculation. Furthermore, deadband feedback scheduling is combined with a variable sampling period algorithm. Deadband is set in the sensor and controller nodes to effectively adjust the information flow of the forward channel and the feedback channel. The proposed scheduling approach can reduce the impact of network conflict and network delay on system stability, make the network resources allocated reasonably, save network data traffic, and improve the overall performance of the NCS. A NCS with five control loops is used as the simulation object and carried out by True Time toolbox. The simulation results show that the proposed scheduling approach can improve output control performance of the system, reduce integral absolute error value of the control loops, and improve network utilization. The overall control performance of the system is improved.
Corporate governance paradigms of hazardous industries: Enduring challenges of Britain’s civil nuclear industry
Authors: Pemberton B.C. , Ng W.
Published: January 2021

This article discusses risk management processes in Britain’s civil nuclear industry from a corporate governance perspective. As an example of a hazardous industry that can inflict catastrophic environmental damage and fatalities, effective governance of Britain’s nuclear industry is a critical issue. Yet the industry’s history of corporate governance suggests that processes of corporate governance have regularly failed to meet core requirements of its stakeholders. A core requirement is for governance designs that recognize the interests of public owner–stakeholders. In meeting this requirement, the article offers a framework for a relationship-driven form of corporate governance that enables meaningful stakeholder engagement in decision-making.
Battered Immigrant Women and the Police: A Canadian Perspective
Authors: Couture-Carron Amanda , Zaidi Arshia U. , Ammar Nawal H.
Published: January 2021

Since the 1970s, the state response to intimate partner violence (IPV) has increasingly become one of criminalization—particularly police intervention. Little is known, however, about marginalized women’s experiences with the police within a context of intimate partner violence in Canada. Drawing on interviews with 90 battered immigrant women, this study examines which women contact the police, why some do not, and what characterizes their experiences when the police are involved in an IPV incident. This study demonstrates that while the women who called the police were demographically similar to those who did not call, the women who called reported much greater levels of physical abuse. Findings indicate that general fear of the police and fear of police being racist or culturally insensitive continue to be important reasons why women do not call the police. Notably, the majority of women who had contact with the police reported the encounter as positive.
The Complex Associations Between Early Childhood Adversity, Heart Rate Variability, Cluster B Personality Disorders, and Aggression
Authors: Jankovic Marija , Bogaerts Stefan , Klein Tuente Stéphanie , Garofalo Carlo , Veling Wim , van Boxtel Geert
Published: January 2021

Early childhood adversity can cause an imbalance in the autonomic function, which may in turn lead to the development of trauma-spectrum disorders and aggressive behavior later in life. In the present study, we investigated the complex associations between early adversity, heart rate variability (HRV), cluster B personality disorders, and self-reported aggressive behavior in a group of 50 male forensic inpatients ( M age = 41.16; SD = 10.72). Structural Equation Modeling analysis revealed that patients with cluster B personality disorders were more likely to have adverse early childhood experiences and reduced sympathetic dominance in response to a threat than patients without cluster B personality disorders. In addition, HRV and cluster B personality disorders did not significantly mediate the association between early childhood adversity and self-reported aggressive behavior. These findings are important for clinical practice to facilitate specific treatment programs for those affected.
Consumer Versus Corporate Moral Responsibilities for Creating a Circular Fashion: Virtue or Accountability?
Authors: Ki Chung-Wha (Chloe) , Ha-Brookshire Jung E
Published: January 2021

Scholars in the fashion discipline have become more attentive to investigating how the fashion business can become more circular. In the past, many of the studies focused on identifying the supporting and/or hindering factors when creating a circular fashion (CF). Despite the insights these studies provide, their contributions are relatively limited in that many of them are exploratory in nature and skewed toward understanding CF from the stance of fashion companies who are situated at the supply side of the fashion economy. In contrast, little attention has been given to how consumers, on the demand side, perceive a CF. We employed a mixed-method approach using 332 respondents’ narrative data and empirically identified whether consumers attribute moral responsibility to fashion companies as well as to themselves for creating a CF and, if so, whether there are any nuanced differences in their perceptions of consumer versus corporate moral responsibilities for a CF.
Sensorless intelligent second-order integral sliding mode maximum power point tracking control for wind turbine system based on wind speed estimation
Authors: Ma Leiming , Xiao Lingfei , Yang Jianfeng , Huang Xinhao , Meng Xiangshuo
Published: January 2021

Aiming at the maximum power point tracking for wind turbine, a sensorless intelligent second-order integral sliding mode control based on wind speed estimation is proposed in this article. The maximum wind energy capture is realized by controlling permanent magnet synchronous motor to adjust the speed of wind turbine. First, an intelligent second-order integral sliding mode control is designed for the speed loop and current loop control, which has fast convergence speed, strong robustness and can effectively reduce chattering. Second, a novel cascade observer based on direct sliding mode observer and extended high-gain observer is used to estimate the rotor speed and position. Besides, combined radial basis function neural network is used to estimate the valid value of wind speed. Both simulation and experiment are implemented, which verify the effectiveness of the proposed strategy under the condition of considering both model uncertainty and external disturbance.
Electron microscopy study of 496 cases of lupus nephritis: A single-center experience
Authors: Bagheri Bahar , Owji Seyed Mohammad , Torabinezhad Simin , Raeisi Shahraki Hadi , Kamalinia Amirhossein , Owji Seyed Hossein , Dehghani Farshad
Published: January 2021

Introduction

Renal involvement is seen in about 40-82% of systemic lupus erythematosus (SLE) Asian patients. The exact diagnosis and classification of lupus nephritis are important for treatment and prognosis. This study aimed to investigate the value of electron microscopy (EM) in the diagnosis and classification of lupus nephritis compared with light microscopy.

Method

In this cross-sectional referral-center 16-year study of lupus nephritis, the final diagnosis was based on the EM study. Primary light microscopy findings were compared with EM diagnosis. Moreover, Immunofluorescence patterns distribution was assessed.

Results

From 496 patients diagnosed with lupus nephritis based on EM, 225(45.4%) of patients were categorized in class IV, followed by 98(19.7%), 93(18.8%), 46(9.3%), and 14(2.8%) who were categorized into classes of II, III, V, and VI respectively. Only 1(0.2%) patient belonged to class I, and 19(3.8%) cases were diagnosed with mixed two classes. Using EM was essential for diagnosing 25.6% of cases taking the correct classification by light microscopy into account; however, disregarding correct classification, this could change to a 7.4% contribution rate of EM. The most common cause of misdiagnosis, disregarding incorrect classification, was inadequate or wrong tissue. Positive associations were detected between tubular atrophy and interstitial fibrosis of both electron and light microscopy with different classes (P < 0.001).

Conclusion

While light microscopy is highly accurate for diagnosing lupus nephritis regardless of correct classification, EM contributes substantially to the correct classification of lupus nephritis types.
A Systematic Review on Barriers to Palliative Care in Oncology
Authors: Parajuli Jyotsana , Hupcey Judith E.
Published: January 2021

The number of people with cancer and the need for palliative care among this population is increasing in the United States. Despite this growing need, several barriers exist to the utilization of palliative care in oncology. The purpose of this study was to synthesize the evidence on the barriers to palliative care utilization in an oncology population. A systematic review of literature was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, CINAHL, and Psych Info databases were used for the literature search. Articles were included if they: 1) focused on cancer, (2) examined and discussed barriers to palliative care, and c) were peer reviewed, published in English, and had an accessible full text. A total of 29 studies (8 quantitative, 18 qualitative, and 3 mixed-methods) were identified and synthesized for this review. The sample size of the included studies ranged from 10 participants to 313 participants. The barriers to palliative care were categorized into barriers related to the patient and family, b) barriers related to providers, and c) barriers related to the healthcare system or policy. The factors identified in this review provide guidance for intervention development to mitigate the existing barriers and facilitate the use palliative care in individuals with cancer.
Macular fibrosis in Coats’ disease demonstrated by Optical Coherence Tomography Angiography – new data toward pathophysiology
Authors: Chwiejczak Katarzyna , Biswas Susmito , Tsamis Emmanouil , Siso-Fuertes Irene , Kasbia Shakti , Stanga Paulo E
Published: January 2021

Purpose:

To analyze if Segmented Swept-Source Optical Coherence Tomography Angiography (SS OCT-A) can provide additional information on morphology and pathophysiology of macular fibrosis in Coats’ patients.

Methods:

A consecutive case series of three male patients (5, 7 and 15 years old), with Coats’ disease-related macular fibrosis (stage 2b-2 patients, 3b-1 patient). SS OCT-A 3×3 mm macular scans of affected eyes were performed.

Results:

In all three cases the inner portion of macular fibrosis displayed a dense network of vessels, continuing into deeper layers. This structure was similar to that observed in retinal angiomatous proliferations (RAP). There was associated loss of the foveal avascular zone. In one case we observed evolution of the lesion.

Conclusion:

SS-OCT imaging of macular fibrosis in Coats’ disease reveals a distinct intralesional vascular structure with elements resembling RAP, probably developing as a secondary process.
Origins and consequences of economic globalization: moving beyond a flawed orthodoxy
Authors: Maswood Syed Javed
Published: January 2021

Contemporary economic globalization is typically seen as a product of both trade and economic liberalization after the Second World War and of technological advances that have made it possible to overcome coordination and management of geographically dispersed production units. Trade liberalization and technological advances were certainly important variables, but I argue that it was neo-protectionist American policies of the early 1980s that provided the initial catalyst for globally networked production processes. American protectionism encouraged Japanese investment in the United States that allowed US car manufacturers to learn the essentials of network manufacturing as practiced by Japanese transplants in the United States. In the next stage of global network manufacturing, liberal trade played a much more pivotal role because the global supply chains could not obviously be maintained without liberal trade. In this paper, I also discuss the likelihood of a reversal and suggest that globalization is unlikely to reversed in a significant way. Liberal trade is essential to the integrity of global supply chain networks, but these new production processes have themselves created a firewall against future systemic protectionism.
Doing nothing? An ethnography of patients’ (In)activity on an acute stroke unit
Authors: Costa Alessia , Jones Fiona , Kulnik Stefan T , Clarke David , Honey Stephanie , Robert Glenn
Published: January 2021

Health research has begun to pay increasing attention to inactivity in its broadest sense as lack of meaningful activity and boredom. Few studies however have taken a critical look at this phenomenon. We explore (in)activity drawing on ethnographic data from observations in an acute stroke unit and post-discharge interviews with stroke survivors and their families. Four themes emerged that explain patients’ (in)activity: (i) planned activities; (ii) ‘doing nothing’, (iii) the material environment of the unit; (iv) interactions with staff. Considering these themes, we seek to problematise received conceptual and methodological approaches to understanding (in)activity. We argue that (in)activity is best conceived not as lack of action or meaning, but as a situated practice encompassing both bodily and mental activities that reflect and reproduce the way in which life is collectively organised within a specific healthcare setting.
Least squares identification of linear sway-yaw manoeuvring coefficients and drag-area parameters of ships
Authors: Raman-Nair Wayne , Gash Robert
Published: January 2021

The purpose of this paper is to present a simple least squares technique for identifying a ship’s linear sway-yaw manoeuvring coefficients and drag-area parameters in current and wind, using measured data. These coefficients are required inputs to a standard three-degree-of-freedom manoeuvring model. The identification method employs the BFGS algorithm which avoids direct computation of the Hessian of the residual function. The results of test simulation problems are discussed and an identification example with measured data is presented. The applicability and limitations of the algorithm are discussed.
Sum rate capacity of non-orthogonal multiple access scheme with optimal power allocation
Authors: Bhardwaj Lokesh , Mishra Ritesh Kumar , Shankar Ravi
Published: January 2021

In this work, the performance of the downlink non-orthogonal multiple access (NOMA) technique is investigated for two users considering optimal power allocation factors. The power domain NOMA differentiates the users based on channel gains by providing different power levels and it is demonstrated that optimal power allocation is only possible when the gain ratio is maximum. Further, the range of optimal power levels is derived for the strong user having better channel conditions. Furthermore, the outage probability (OP) has been derived for ordered NOMA in the downlink through the cumulative density function-based approach. The simulation results demonstrate the improvement in sum rate capacity for optimal power allocation as compared to random power allocation, and the OP reduces with the signal-to-noise ratio more sharply for the stronger user.
The Lifespan of a University–Industry Partnership: A Case Study
Authors: Edmunds Andrew , Boettcher Michelle
Published: January 2021

This case study presents a fictionalized narrative account of a university–industry partnership across a 5-year period. The case presented involves a hypothetical public research university and their partnership with a Fortune 500 company. A brief background on the history of university–industry partnerships is provided with highlights of key policies and theoretical models for partnership development. Teaching notes, activities, and additional suggested readings are provided to aid in analysis and reflection.
Accuracy of apparent diffusion coefficient in differentiation of glioblastoma from metastasis
Authors: Beig Zali Sanaz , Alinezhad Farbod , Ranjkesh Mahnaz , Daghighi Mohammad H , Poureisa Masoud
Published: January 2021

Background

Brain metastasis and glioblastoma multiforme are two of the most common malignant brain neoplasms. There are many difficulties in distinguishing these diseases from each other.

Purpose

The purpose of this study was to determine whether the mean apparent diffusion coefficient and absolute standard deviation derived from apparent diffusion coefficient measurements can be used to differentiate glioblastoma multiforme from brain metastasis based on cellularity levels.

Material and methods

Magnetic resonance images of 34 patients with histologically verified brain tumors were evaluated retrospectively. Apparent diffusion coefficient and standard deviation values were measured in the enhancing tumor, peritumoral region, and contralateral healthy white matter. Then, to determine whether there was a statistical difference between brain metastasis and glioblastoma multiforme, we analyzed different variables between the two groups.

Results

Neither mean apparent diffusion coefficient values and ratios nor standard deviation values and ratios were significantly different between glioblastoma multiforme and brain metastasis. Receiver operating characteristic curve analysis of the logistic model with backward stepwise feature selection yielded an area under the curve of 0.77, a specificity of 84%, a sensitivity of 67%, a positive predictive value of 83.33%, and a negative predictive value of 78.26% for distinguishing between glioblastoma multiforme and brain metastasis. The absolute standard deviation and standard deviation ratios were significantly higher in the peritumoral edema compared to the tumor region in each case.

Conclusion

Apparent diffusion coefficient values and ratios, as well as standard deviation values and ratios in peritumoral edema, cannot be used to differentiate edema with infiltration of tumor cells from vasogenic edema. However, standard deviation values could successfully characterize areas of peritumoral edema from the tumoral region in each case.
Endoscopic cubital tunnel decompression – Review of the literature
Authors: Fok Margaret Woon Man , Cobb Tyson , Bain Gregory I
Published: January 2021

Cubital tunnel syndrome is the second most common compressive neuropathy of the upper limb. Endoscopic cubital tunnel decompression has gained popularity in recent years as this enables surgeons to achieve decompression of the ulnar nerve along its course using a small incision. This article describes the technical peals in performing endoscopic cubital tunnel decompression. In conditions which anterior transposition of the ulnar nerve is needed, subcutaneous transposition can be performed under endoscopic guidance. In addition, current literature is reviewed, and outcomes are presented. While short term results are encouraging, further prospective randomized study with longer follow-up is recommended.
The Influence of Relationship Lending on SMEs Loan Repayment Performance
Authors: Mori Neema , Ng’urah Godfrey
Published: January 2021

The study examined the influence of relationship lending on repayment performance of small- and medium-enterprise (SME) credit facilities. Four hypotheses were developed and tested using data from 395 sampled borrowers of the largest Tanzanian bank. Data for independent variables were obtained through an administered questionnaire while the data for dependent variable were obtained from the borrowers’ records with the bank. Descriptive and econometric analyses were conducted. Findings show that length and depth of relationship between bank and customers positively and significantly influence the repayment performance. Contrary to other empirical works, the findings revealed the scope of the relationship has no influence on repayment performance, while proximity has a negative association with repayment. The article contributes to the debate over the challenges of ex ante selection (adverse selection) and ex post action (moral hazards) by examining an aspect of trust. The bank and the borrower need to develop and cultivate relationship for the loan to perform well; hence, establishing mutual trust and building a long-term relationship is ideal. The article also contributes to the concept of social collateral which has not received much attention in the literature. With the current effects of COVID-19 on the banking and SME sectors, a major mitigator is to rely on their relationship banking for loan repayment, restructuring, and additional loans to boost businesses. Focusing on transactional banking might prove difficult when turmoil and unexpected pandemic like COVID-19 hits the bank and the firm.
Linking authentic leadership, moral voice and silence—A serial mediation model comprising follower constructive cognition and moral efficacy
Authors: Frömmer Dirk , Hollnagel Gustav , Franke-Bartholdt Luise , Strobel Anja , Wegge Jürgen
Published: January 2021

Authentic leadership is widely considered a positive form of moral leadership that emphasizes a leader’s self-awareness, self-concordance, and modeling of self-regulatory behaviors. It is expected that authentic leaders foster moral employee behavior. However, empirical evidence for this assumption with a clear focus on the moral domain is still rather scarce. Furthermore, little is known about mediating mechanisms, especially pertaining to self-regulation of followers. Our research focused on two important facets of moral employee behavior: voice and silence. We (a) examined relationships between authentic leadership, moral voice, and two major forms of moral silence (quiescent and acquiescent) and (b) tested follower constructive cognition and moral efficacy as self-regulatory mechanisms in a serial mediation model. We conducted a cross-sectional study with employees from different organizations ( n = 295). As expected, analyses indicated that authentic leadership is positively related to self-reported voice and negatively to self-reported silence on moral issues. Pertaining to the outcomes quiescent moral silence and moral voice, results revealed a serial mediation effect via constructive cognition and moral efficacy. Furthermore, unique indirect effects of each mediator were found. Thus, authentic leadership can enhance moral behavior mediated by follower constructive cognition and moral efficacy. Based on these insights, new interventions for overcoming silence and promoting voice in organizations can be designed.
Hrabákite, Ni9PbSbS8, a new member of the hauchecornite group from Příbram, Czech Republic
Authors: Sejkora Jiří , Škácha Pavel , Plášil Jakub , Dolníček Zdeněk , Ulmanová Jana
Published: January 2021

The new mineral hrabákite (IMA2020-034) was found in siderite–sphalerite gangue with minor dolomite–ankerite at the dump of shaft No. 9, one of the mines in the abandoned Příbram uranium and base-metal district, central Bohemia, Czech Republic. Hrabákite is associated with Pb-rich tučekite, Hg-rich silver, stephanite, nickeline, millerite, gersdorffite, sphalerite and galena. The new mineral occurs as rare prismatic crystals up to 120 μm in size and allotriomorphic grains. Hrabákite is grey with a brownish tint. Mohs hardness isca. 5–6; the calculated density is 6.37 g.cm–3. In reflected light, hrabákite is grey with a brown hue. Bireflectance is weak and pleochroism was not observed. Anisotropy under crossed polars is very weak (brownish tints) to absent. Internal reflections were not observed. Reflectance values of hrabákite in air (Rmin–Rmax, %) are: 39.6–42.5 at 470 nm, 45.0–47.5 at 546 nm, 46.9–49.2 at 589 nm and 48.9–51.2 at 650 nm). The empirical formula for hrabákite, based on electron-microprobe analyses (n= 11), is (Ni8.91Co0.09Fe0.03)9.03(Pb0.94Hg0.04)0.98(Sb0.91As0.08)0.99S7.99. The ideal formula is Ni9PbSbS8, which requires Ni 47.44, Pb 18.60, Sb 10.93 and S 23.03, total of 100.00 wt.%. Hrabákite is tetragonal,P4/mmm,a= 7.3085(4),c= 5.3969(3) Å, withV= 288.27(3) Å3andZ= 1. The strongest reflections of the calculated powder X-ray diffraction pattern [d, Å (I)(hkl)] are: 3.6543(57)(200); 3.2685(68)(210); 2.7957(100)(211); 2.3920(87)(112); 2.3112(78)(310); 1.8663(74)(222); and 1.8083(71)(302). According to the single-crystal X-ray diffraction data (Rint= 0.0218), the unit cell of hrabákite is undoubtedly similar to the cell reported for tučekite. The structure contains four metal cation sites, two Sb (Sb1 dominated by Pb2+) and two Ni (with minor Co2+content) sites. The close similarity in metrics between hrabákite and tučekite is due to similar bond lengths of Pb–S and Sb–S pairs. Hrabákite is named after Josef Hrabák, the former professor of the Příbram Mining College.
New arsenate minerals from the Arsenatnaya fumarole, Tolbachik volcano, Kamchatka, Russia. XV. Calciojohillerite, NaCaMgMg2(AsO4)3, a member of the alluaudite group
Authors: Pekov Igor V. , Koshlyakova Natalia N. , Agakhanov Atali A. , Zubkova Natalia V. , Belakovskiy Dmitry I. , Vigasina Marina F. , Turchkova Anna G. , Sidorov Evgeny G. , Pushcharovsky Dmitry Yu.
Published: January 2021

The new alluaudite-group mineral calciojohillerite is one of the major arsenates in sublimates of the Arsenatnaya fumarole at the Second scoria cone of the Northern Breakthrough of the Great Tolbachik Fissure Eruption, Tolbachik volcano, Kamchatka, Russia. In middle zones of the fumarole, calciojohillerite is associated with hematite, tenorite, johillerite, nickenichite, bradaczekite, badalovite, tilasite, lammerite, ericlaxmanite, aphthitalite-group sulfates, langbeinite, calciolangbeinite, anhydrite, sanidine, fluorophlogopite, fluoborite, cassiterite, pseudobrookite, rutile, sylvite and halite. In deep zones it occurs in association with anhydrite, diopside, hematite, svabite, berzeliite, schäferite, forsterite, magnesioferrite, ludwigite, rhabdoborite-group fluoroborates, powellite, baryte, fluorapatite, udinaite, arsenudinaite and paraberzeliite. Calciojohillerite forms prismatic crystals up to 1 cm long, their aggregates and crystal crusts up to 0.5 m2. It is transparent, colourless, pale green, pale yellow, light blue, pale lilac or pink, with vitreous lustre. The mineral is brittle, with imperfect cleavage. The Mohs hardness is 3½. Dcalc is 3.915 g cm–3. Calciojohillerite is optically biaxial (–), α = 1.719(3), β = γ = 1.732(3); 2Vmeas. = 15(10)°. Chemical composition (wt.%, electron-microprobe; holotype) is: Na2O 7.32, K2O 0.10, CaO 6.82, MgO 20.31, MnO 0.68, CuO 0.27, ZnO 0.02, Al2O3 0.56, Fe2O3 3.53, TiO2 0.01, SiO2 0.03, P2O5 1.25, V2O5 0.10, As2O5 58.77, SO3 0.13, total 99.90. The empirical formula based on 12 O atoms is (Na1.30K0.01Ca0.67Mg2.78Mn0.05Cu0.02Al0.06Fe3+0.24)Σ5.13(As2.83P0.10S0.01V0.01)Σ2.95O12. Calciojohillerite is monoclinic, C2/c, a = 11.8405(3), b = 12.7836(2), c = 6.69165(16) Å, β = 112.425(3)°, V = 936.29(4) Å3 and Z = 4. The crystal structure was solved from single-crystal X-ray diffraction data, R1 = 0.0227. Calciojohillerite is isostructural with other alluaudite-group minerals. Its simplified crystal chemical formula is A(1)CaA(1)′□A(2)□A(2)′NaM(1)MgM(2)Mg2(AsO4)3 (□ = vacancy). The idealised formula is NaCaMg3(AsO4)3, or, according to the nomenclature of alluaudite-group arsenates, NaCaMgMg2(AsO4)3. Calciojohillerite is named as an analogue of johillerite NaCu2+MgMg2(AsO4)3 with species-defining Ca instead of Cu in the ideal formula.
The use of luspatercept for thalassemia in adults
Authors: Cappellini Maria Domenica , Taher Ali T.
Published: January 2021

Luspatercept is an activin receptor ligand trap that has been shown to enhance late-stage erythropoiesis in animal models of β-thalassemia. A multicenter, international, phase 2 dose-finding study was initiated in adult patients with β-thalassemia, either non–transfusion-dependent thalassemia (NTDT) or transfusion-dependent thalassemia (TDT). Positive results of the phase 2 study paved the way to a randomized phase 3 clinical trial (BELIEVE) to assess the efficacy and safety of luspatercept. The BELIEVE trial is a randomized, double-blind, placebo-controlled phase 3 trial. Three hundred thirty-six patients aged ≥18 years with TDT (regularly transfused, 6-20 red blood cell units within 24 weeks before randomization) were included in the trial. Patients received luspatercept or placebo subcutaneously every 21 days for ≥48 weeks and best supportive care. Forty-eight of 224 patients (21.4%) in the luspatercept group achieved the primary end points (≥33% reduction in transfusion burden) compared with those in the placebo group (4.5%; P < .001). Moreover, more patients had a ≥33% reduction in transfusion burden during any rolling 12-week interval (70.5% vs 29.5%) or any 24-week interval (41.1% vs 2.7%) with luspatercept than with the placebo. Transfusion independence was achieved by 11% of patients in the luspatercept group. Transient adverse events were more frequent with luspatercept than with placebo, but were manageable. Luspatercept was approved by the US Food and Drug Administration in 2019 and by the European Medicines Agency in 2020. The luspatercept trial is registered on www.clinicaltrials.gov at #NCT01749540 and the BELIEVE trial at #NCT02604433.
Overcoming resistance to targeted therapies in chronic lymphocytic leukemia
Authors: Skånland Sigrid S. , Mato Anthony R.
Published: January 2021

Insight into the critical role of B-cell receptor signaling for the pathogenesis of chronic lymphocytic leukemia (CLL) led to the development of targeted therapies directed at key regulators of cell survival. Agents targeting B-cell lymphoma-2 protein, Bruton’s tyrosine kinase (BTK), and phosphatidylinositol 3-kinase are approved for treatment of CLL, and have significantly improved the disease management. Nevertheless, acquired resistance to the targeted therapies is a challenge still to be resolved. The mechanisms underlying resistance are becoming clearer, and include secondary mutations within the drug target and activation of bypass pathways. This knowledge has allowed development of strategies to prevent and overcome treatment resistance. Approaches to prevent resistance include targeting bypass mechanisms by combination therapies, temporally sequencing of therapies, improved clinical trial designs, and real-time monitoring of patient response. A rational design of drug sequencing may secure effective treatment options at the relapsed setting. Next-generation inhibitors and bispecific antibodies have the potential to overcome resistance to the BTK inhibitor ibrutinib. Immunotherapy, including chimeric antigen receptor-modified T-cell therapy, is explored for relapsed CLL. Here, recent advances that have contributed to the understanding of resistance to targeted therapies in CLL are discussed. Strategies for managing resistance are reviewed, including translational, real-world, and clinical perspectives.
A-to-I editing of miR-200b-3p in airway cells is associated with moderate-to-severe asthma
Authors: Magnaye Kevin M. , Naughton Katherine A. , Huffman Janel , Hogarth D. Kyle , Naureckas Edward T. , White Steven R. , Ober Carole
Published: January 2021

Background

Asthma is a chronic lung disease characterised by persistent airway inflammation. Altered microRNA (miRNA)-mediated gene silencing in bronchial epithelial cells (BECs) has been reported in asthma, yet adenosine deaminase acting on RNA (ADAR)-mediated miRNA editing in asthma remains unexplored.

Methods

We first identified adenosine to inosine (A-to-I) edited sites in miRNAs in BECs from 142 adult asthma cases and controls. A-to-I edited sites were tested for associations with asthma severity and clinical measures of asthma. Paired RNA sequencing data were used to perform pathway enrichments and test for associations with bioinformatically predicted target genes of the unedited and edited miRNAs.

Results

Of 19 A-to-I edited sites detected in these miRNAs, one site at position 5 of miR-200b-3p was edited less frequently in cases compared with controls (pcorrected=0.013), and especially compared with cases with moderate (pcorrected=0.029) and severe (pcorrected=3.9×10−4), but not mild (pcorrected=0.38), asthma. Bioinformatic prediction revealed 232 target genes of the edited miR-200b-3p, which were enriched for both interleukin-4 and interferon-γ signalling pathways, and included theSOCS1(suppressor of cytokine signalling 1) gene.SOCS1was more highly expressed in moderate (pcorrected=0.017) and severe (pcorrected=5.4×10−3) asthma cases compared with controls. Moreover, both miR-200b-3p editing andSOCS1were associated with bronchoalveolar lavage eosinophil levels.

Conclusions

Reduced A-to-I editing of position 5 of miR-200b-3p in lower airway cells from moderate-to-severe asthmatic subjects may lead to overexpression ofSOCS1and impaired cytokine signalling. We propose ADAR-mediated editing as an epigenetic mechanism contributing to features of moderate-to-severe asthma in adulthood.
Exercise-induced bronchoconstriction and bronchodilation: investigating the effects of age, sex, airflow limitation and FEV1
Authors: Satia Imran , Priel Eldar , Al-Khazraji Baraa K. , Jones Graham , Freitag Andy , O'Byrne Paul M. , Killian Kieran J.
Published: January 2021

Exercise-induced bronchoconstriction (EIBc) is a recognised response to exercise in asthmatic subjects and athletes but is less well understood in an unselected broad population. Exercise-induced bronchodilation (EIBd) has received even less attention. The objective of this study was to investigate the effects of age, sex, forced expiratory volume in 1 s (FEV1) and airflow limitation (FEV1/forced vital capacity (FVC) <0.7) on the prevalence of EIBc and EIBd.

This was a retrospective study based on incremental cardiopulmonary exercise testing on cycle ergometry to symptom limitation performed between 1988 and 2012. FEV1was measured before and 10 min after exercise. EIBc was defined as a percentage fall in FEV1post-exercise below the 5th percentile, while EIBd was defined as a percentage increase in FEV1above the 95th percentile.

35 258 subjects aged 6–95 years were included in the study (mean age 53 years, 60% male) and 10.3% had airflow limitation (FEV1/FVC <0.7). The lowest 5% of subjects demonstrated a ≥7.6% fall in FEV1post-exercise (EIBc), while the highest 5% demonstrated a >11% increase in FEV1post-exercise (EIBd). The probability of both EIBc and EIBd increased with age and was highest in females across all ages (OR 1.76, 95% CI 1.60–1.94; p<0.0001). The probability of EIBc increased as FEV1% pred declined (<40%: OR 4.38, 95% CI 3.04–6.31; p<0.0001), with a >2-fold increased likelihood in females (OR 2.31, 95% CI 1.71–3.11; p<0.0001), with a trend with airflow limitation (p=0.06). The probability of EIBd increased as FEV1% pred declined, in the presence of airflow limitation (OR 1.55, 95% CI 1.24–1.95; p=0.0001), but sex had no effect.

EIBc and EIBd can be demonstrated at the population level, and are influenced by age, sex, FEV1% pred and airflow limitation.
Treatable cardiac disease in hospitalised COPD exacerbations
Authors: Leong Paul , MacDonald Martin I. , King Paul T. , Osadnik Christian R. , Ko Brian S. , Landry Shane A. , Hamza Kais , Kugenasan Ahilan , Troupis John M. , Bardin Philip G.
Published: January 2021

Introduction

Acute exacerbations of COPD (AECOPD) are accompanied by escalations in cardiac risk superimposed upon elevated baseline risk. Appropriate treatment for coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF) could improve outcomes. However, securing these diagnoses during AECOPD is difficult, so their true prevalence remains unknown, as does the magnitude of this treatment opportunity. We aimed to determine the prevalence of severe CAD and severe HFrEF during hospitalised AECOPD using dynamic computed tomography (CT).

Methods

A cross-sectional study of 148 patients with hospitalised AECOPD was conducted. Dynamic CT was used to identify severe CAD (Agatston score ≥400) and HFrEF (left ventricular ejection fraction ≤40% and/or right ventricular ejection fraction ≤35%).

Results

Severe CAD was detected in 51 of 148 patients (35%), left ventricular systolic dysfunction was identified in 12 cases (8%) and right ventricular systolic dysfunction was present in 18 (12%). Clinical history and examination did not identify severe CAD in approximately one-third of cases and missed HFrEF in two-thirds of cases. Elevated troponin and brain natriuretic peptide did not differentiate subjects with severe CAD from nonsevere CAD, nor distinguish HFrEF from normal ejection fraction. Undertreatment was common. Of those with severe CAD, only 39% were prescribed an antiplatelet agent, and 53% received a statin. Of individuals with HFrEF, 50% or less received angiotensin blockers, beta blockers or antimineralocorticoids.

Conclusion

Dynamic CT detects clinically covert CAD and HFrEF during AECOPD, identifying opportunities to improve outcomesviawell-established cardiac treatments.
Plasmonic Chiral Metasurface Absorber Based on Bilayer Fourfold Twisted Semicircle Nanostructure at Optical Frequency
Authors: Cheng Yongzhi , Chen Fu , Luo Hui
Published: January 2021

In this paper, we present a plasmonic chiral metasurface absorber (CMSA), which can achieve high selective absorption for right-handed and left-handed circular polarization (RCP, “+”, and LCP, “−”) lights at optical frequency. The CMSA is composed of a dielectric substrate sandwiched with bi-layer fourfold twisted semicircle metal nanostructure. The proposed CMSA has a strong selective absorption band, where absorption peaks for LCP and RCP lights occur at different resonance frequencies, reflecting the existence of a significant circular dichroism (CD) effect. It is shown that the absorbance of the CMSA can reach to 93.2% for LCP light and 91.6% for RCP light, and the maximum CD magnitude is up to 0.85 and 0.91 around 288.5 THz and 404 THz, respectively. The mechanism of the strong chiroptical response of the CMSA is illustrated by electric fields distributions of the unit-cell nanostructure. Furthermore, the influence of the geometry of the proposed CMSA on the circular polarization selective absorption characterization is studied systematically.
Genomic regions associated with stripe rust resistance against the Egyptian race revealed by genome-wide association study
Authors: Abou-Zeid Mohamed A. , Mourad Amira M. I.
Published: January 2021

Background

Wheat stripe rust (caused by Puccinia striiformis f. sp. Tritici), is a major disease that causes huge yield damage. New pathogen races appeared in the last few years and caused a broke down in the resistant genotypes. In Egypt, some of the resistant genotypes began to be susceptible to stripe rust in recent years. This situation increases the need to produce new genotypes with durable resistance. Besides, looking for a new resistant source from the available wheat genotypes all over the world help in enhancing the breeding programs.

Results

In the recent study, a set of 103-spring wheat genotypes from different fourteen countries were evaluated to their field resistant to stripe rust for two years. These genotypes included 17 Egyptian genotypes from the old and new cultivars. The 103-spring wheat genotypes were reported to be well adapted to the Egyptian environmental conditions. Out of the tested genotypes, eight genotypes from four different countries were found to be resistant in both years. Genotyping was carried out using genotyping-by-sequencing and a set of 26,703 SNPs were used in the genome-wide association study. Five SNP markers, located on chromosomes 2A and 4A, were found to be significantly associated with the resistance in both years. Three gene models associated with disease resistance and underlying these significant SNPs were identified. One immune Iranian genotype, with the highest number of different alleles from the most resistant Egyptian genotypes, was detected.

Conclusion

the high variation among the tested genotypes in their resistance to the Egyptian stripe rust race confirming the possible improvement of stripe rust resistance in the Egyptian wheat genotypes. The identified five SNP markers are stable and could be used in marker-assisted selection after validation in different genetic backgrounds. Crossing between the immune Iranian genotype and the Egyptian genotypes will improve stripe rust resistance in Egypt.
Clinical characteristics, treatment and prognosis of children with unilateral retinoblastoma and intracranial segment of Retrobulbar optic nerve invasion
Authors: Wang Yi-Zhuo , Zhang Yi , Huang Dong-Sheng , Shi Ji-Tong , Ma Jian-Min , Li Bin , Xu Xiao-Lin , Zhou Yan , Gu Hua-Li
Published: January 2021

Background

To analyze the clinical characteristics, treatment and prognosis of children with unilateral retinoblastoma (RB) and intracranial segment of retrobulbar optic nerve invasion.

Methods

A total of 14 children with unilateral RB and intracranial segment of retrobulbar optic nerve invasion were enrolled in this retrospective study from January 2009 to December 2018. Clinical characteristics, treatment and prognosis were collected and analyzed. Survival curves were calculated by Kaplan-Meier method.

Results

Of 14 cases, there were 7 male and 7 female, ranging in age from 22.85 to 121.97 months (median, 41.03 months). Seventy-one percent of patients came from first-tier cities in China and effected in the left eye. Magnetic resonance imaging (MRI) results indicated that all patients presented with thickened and enhanced optic nerve and intracranial segment of optic nerve invasion. Nine patients received comprehensive therapeutic regimen (chemotherapy, eye enucleation, radiotherapy and intrathecal therapy). The patients were followed up to December 2019, with a median follow-up of 20.6 months. The median disease specific survival was 48.99 ± 8.62 months, and the overall survival (OS) rate was 64.3%. Radiotherapy and comprehensive therapeutic regimen had significant impact on survival time (all p < 0.05).

Conclusions

The overall prognosis of unilateral RB patients with intracranial segment of retrobulbar optic nerve invasion was poor. Chemotherapy and surgical treatment were necessary, but more attention should be paid to radiotherapy and intrathecal therapy for improving prognosis.
Acute development of syringomyelia following TBM in a pediatric case
Authors: Wen Ningyuan , Zhao Fumin , Zhu Yu , Jia Fenglin , Wan Chaomin , Wen Yang
Published: January 2021

Background

Syringomyelia secondary to tuberculous meningitis (TBM) is rarely reported, and is usually a late complication. Acute development of syringomyelia following TBM is an exceedingly rare condition with only a few cases published in adults and no previous reports in children.

Case presentation

We present a case of syringomyelia as an acute complication of TBM in a 12-year-old boy despite appropriate chemotherapy. The patient developed spastic paraplegia of the lower limbs with fecal and urinary retention seventeen days after the initial symptoms of TBM. He was managed successfully with continued chemotherapy and high-dose intravenous immunoglobulin (IVIG).

Conclusions

This case reminds us that syrinx formation may be responsible for early neurological deterioration in children being managed for TBM. IVIG may be considered as an effective treatment option for this situation.
In the presence of TGF-β1, Asperosaponin VI promotes human mesenchymal stem cell differentiation into nucleus pulposus like- cells
Authors: Niu Yong-tao , Xie Lin , Deng Rong-Rong , Zhang Xiao-yu
Published: January 2021

Background

The regeneration of nucleus pulposus (NP) cells is an effective method to prevent intervertebral disc degeneration (IVDD). In this study, we investigated the role of Asperosaponin VI (ASA VI), isolated from a traditional Chinese medicine (TCM), the root of Dipsacus asper Wall, in promoting human mesenchymal stem cell (HMSC) proliferation and differentiation into NP-like cells and explored the possible mechanism of action.

Methods

The effects of ASA VI on HMSC viability and proliferation were determined by the XTT method and EDU staining. Then, Real-time qPCR, immunocytochemistry and immunofluorescence assays were used to measure the effect of ASA VI on the expression of extracellular matrix (ECM) components, such as COL2A1, aggrecan, SOX9, KRT19, PAX1, and glycosaminoglycans (GAGs), in NP cells. In addition, Western blot assay was used to measure the expression of p-ERK1/2 and p-smad2/3.

Results

ASA VI was able to promote the proliferation and differentiation of HMSCs into NP-like cells, and the optimum concentration was 1 mg/L. Western blot assay indicated that the possible mechanism might be related to the activation of p-ERK1 / 2 and p-Smad2 / 3.

Conclusions

ASA VI can promote the proliferation and differentiation of HMSCs into NP-like cells, which can potentially be used as a treatment for IVDD.
The pro-apoptosis effects of Echinacea purpurea and Cannabis sativa extracts in human lung cancer cells through caspase-dependent pathway
Authors: Hosami Fatemeh , Manayi Azadeh , Salimi Vahid , Khodakhah Farshad , Nourbakhsh Mitra , Nakstad Britt , Tavakoli-Yaraki Masoumeh
Published: January 2021

Background

Considering the advantages of using medicinal herbs as supplementary treatments to sensitize conventional anti-cancer drugs, studying functional mechanisms and regulatory effects ofEchinacea purpurea(as a non-cannabinoid plant) andCannabis sativa(as a cannabinoid plant) are timely and required. The potential effects of such herbs on lung cancer cell growth, apoptosis, cell cycle distribution, cellular reactive oxygen species (ROS) level, caspase activity and their cannabinomimetic properties on the CB2 receptor are addressed in the current study.

Methods

The cytotoxic effect of both herb extracts on the growth of lung cancer cells (A549) was assessed using the MTT assay. The annexin-V-FITC staining and propidium iodide (PI) staining methods were applied for the detection of apoptosis and cell cycle distribution using flow cytometry. The cellular level of ROS was measured using 7′-dichlorofluorescin diacetate (DCFH-DA) as a fluorescent probe in flow cytometry. The caspase 3 activity was assessed using a colorimetric assay Kit.

Results

Echinacea purpurea(EP) root extract induced a considerable decrease in A549 viable cells, showing a time and dose-dependent response. The cell toxicity of EP was accompanied by induction of early apoptosis and cell accumulation at the sub G1 phase of the cell cycle. The elevation of cellular ROS level and caspase 3 activity indicate ROS-induced caspase-dependent apoptosis following the treatment of A549 cells by EP extract. The observed effects of EP extract on A549 growth and death were abrogated following blockage of CB2 using AM630, a specific antagonist of the CB2 receptor. Increasing concentrations ofCannabis sativa(CS) induced A549 cell death in a time-dependent manner, followed by induction of early apoptosis, cell cycle arrest at sub G1 phase, elevation of ROS level, and activation of caspase 3. The CB2 blockage caused attenuation of CS effects on A549 cell death which revealed consistency with the effects of EP extract on A549 cells.

Conclusions

The pro-apoptotic effects of EP and CS extracts on A549 cells and their possible regulatory role of CB2 activity might be attributed to metabolites of both herbs. These effects deserve receiving more attention as alternative anti-cancer agents.

Graphical abstract