bluuebunny/crossref_metadata_2025 huggingface dataset:
A Quantitative Relationship Analysis of Industry Shifts and Trade Restructuring in ASEAN Based on Multiregional Computable General Equilibrium Models
Authors: Xu Luyuan
Published: February 2021

This paper provides an in‐depth study and analysis of the quantitative relationship between ASEAN industry transfer and nuclear trade restructuring through the multiregional computable general equilibrium (CGE) model and categorizes the ten major projects and 57 subprojects covered by the ASEAN Information Port project investment into construction, information technology, and telecommunications, according to the key directions of investment. We design and simulate the changes in production activities, trade activities, and the balance of payments behaviour of the national economy affected by the project’s investment under 10 types of investment amount scenarios and prepare the corresponding social accounting matrix (SAM). Increased trade openness increases external risks and instability of the economy and fiscal revenues. At the same time, it creates other potential problems for the country such as environmental pollution and leading to unfair competition. Under free trade conditions, some manufacturers may choose to produce inputs that are not environmentally friendly to reduce costs, thereby harming the environment. For infant industries, if the government does not provide them with short‐term protection or supportive policies, these new or developing infant industries may not have strong international competitiveness and may be vulnerable to the attacks of mature industries in the world. Therefore, based on the study of the influence of tax policy on trade openness, this paper examines the impact of changes in trade openness on a country’s economic environment and takes tax revenue as an example to conduct an empirical analysis and improve the factors that need to be considered when adjusting tax policy.
A Digital Microscopic Inspection of Dentinal Defects after Using Endodontic Retreatment Files
Authors: AbuMostafa Ammar , Almoqayyad Hala , Mohammad Al-Omari
Published: February 2021

Aim. The study aimed at evaluating the incidence of dentinal defects after root canal retreatment with ProTaper Universal retreatment (PTUR) and XP-endo Shaper and Finisher R (XP). Materials and Methods. Sixty extracted single-rooted human premolars were selected and divided into 4 groups of 15 teeth each. In the negative control group, the teeth were left unprepared. In the positive control group, the teeth were prepared with ProTaper Next and obturated with no further retreatment. In the PTUR and XP groups, the teeth were prepared and obturated followed by removal of the filling material at body temperature using PTUR and XP instruments, respectively. The roots were then sectioned at 3, 6, and 9 mm from the apex and observed under a digital microscope to detect defects. Results. PTUR group showed significantly higher (

p

value <0.05) incidence of defects than the other groups. Comparison of no defects versus defects between groups in different areas of root canals demonstrated significant difference among the groups in the apical and cervical regions. Conclusion. Within the limitations of the present study, PTUR files created significantly more dentinal defects than XP files, with most of those defects at the cervical and apical areas of the root canals.
Numerical Investigation of Dissolved Oxygen Transportation through a Coupled SWE and Streeter–Phelps Model
Authors: Wu Jiaxin , Yu Xiaoxiang
Published: February 2021

Dissolved oxygen (DO) reflects the self-purification ability of a water body and is also an important indicator for quantifying the water quality. The morphological changes in the cross sections of river channels will affect the hydraulic conditions, and the distribution of pollutants and DO may also be affected, possibly resulting in local oxygen deficits and pollution. To effectively predict the water quality, a coupled model is introduced in this study. The shallow water equation (SWE) is adopted to calculate the hydrodynamic processes, and the modified Streeter–Phelps model is further coupled with the SWE model to evaluate the reaeration. By applying this model, mass transportation and reaeration in rivers are analyzed. The influences of the sudden cross-sectional changes in the river channel on the DO distribution and the reaeration ability are identified. The results reveal that a certain degree of expansion in the river is conducive to reaeration and can also accelerate the consumption of pollutants through the water body’s self-purification. DO transport in two real terrains, including a mountain basin and plain river, is extensively investigated, and the results indicate that the morphological characteristics in the mountain basin will cause the concentration distribution to form inside dead zones, while in the plain, the distribution will form a fan-shaped downstream zone.
Neural Network Optimization Method and Its Application in Information Processing
Authors: Wang Pin , Wang Peng , Fan En
Published: February 2021

Neural network theory is the basis of massive information parallel processing and large-scale parallel computing. Neural network is not only a highly nonlinear dynamic system but also an adaptive organization system, which can be used to describe the intelligent behavior of cognition, decision-making, and control. The purpose of this paper is to explore the optimization method of neural network and its application in information processing. This paper uses the characteristic of SOM feature map neural network to preserve the topological order to estimate the direction of arrival of the array signal. For the estimation of the direction of arrival of single-source signals in array signal processing, this paper establishes a uniform linear array and arbitrary array models based on the distance difference vector to detect DOA. The relationship between the DDOA vector and the direction of arrival angle is regarded as a mapping from the DDOA space to the AOA space. For this mapping, through derivation and analysis, it is found that there is a similar topological distribution between the two variables of the sampled signal. In this paper, the network is trained by uniformly distributed simulated source signals, and then the trained network is used to perform AOA estimation effect tests on simulated noiseless signals, simulated Gaussian noise signals, and measured signals of sound sources in the lake. Neural network and multisignal classification algorithms are compared. This paper proposes a DOA estimation method using two-layer SOM neural network and theoretically verifies the reliability of the method. Experimental research shows that when the signal-to-noise ratio drops from 20 dB to 1 dB in the experiment with Gaussian noise, the absolute error of the AOA prediction is small and the fluctuation is not large, indicating that the prediction effect of the SOM network optimization method established in this paper does not vary. The signal-to-noise ratio drops and decreases, and it has a strong ability to adapt to noise.
Lyme Disease Misinterpreted as Child Abuse
Authors: Pan Tommy , Nasreddine Adam , Trivellas Myra , Hennrikus William L.
Published: February 2021

Child abuse is one of the most common causes for child fatality in the United States. Inaccurate reporting of child abuse combined with scarcity of resources for child abuse evaluations can lead to unintended consequences for children and their families. The differential diagnosis of child abuse is varied. To our knowledge, there are no reports in the literature on Lyme disease mimicking child abuse. The current study presents the case of a child from an endemic area for Lyme disease presenting with skin bruising, fracture, and swollen knee. The child was reported for child abuse by the pediatrician and then referred to the orthopaedic surgeon for fracture care.
Fast Adaptive Character Animation Synthesis Based on Greedy Algorithm
Authors: Zhu Yanqiu , Chen Qixing , Liu Jing , Tian Xiaoying
Published: February 2021

On the premise of ensuring the animation effect and real‐time performance, it is of great significance and value for large‐scale group character animation synthesis how to reduce the disaster coincidence degree among various models of fast adaptive character animation synthesis. The realization method of object‐oriented finite state machine is studied in detail. Finite state machine (FSM) is an efficient behavior modeling method, which can describe the behavioral decisions of fast adaptive character animation synthesis in a complex virtual environment. Based on the implementation defects of the finite state machine in the traditional structure, using object‐oriented thinking, combined with the state design mode, we further studied a finite state machine implementation method based on object‐oriented technology. This achieves code reuse and simple program maintenance. The effect is extensible and effectively overcomes the shortcomings of traditional character animation synthesis. Secondly, the multipath matching tracking algorithm of the greedy algorithm is studied to generate multiple candidate sets through multiple paths, and finally, the candidate set with the minimum residual error is selected as the estimated support set, so as to improve the reconstruction performance. Further, based on the idea of multipath, using the regularization method of the ROMP algorithm, the regularized multipath matching tracking RMSP algorithm is proposed. It uses the regularized subset method to generate multiple paths and chooses the path with the fastest residual reduction as the support set of this iteration. The simulation results show that the RMSP algorithm has better reconstruction performance than the SP algorithm.
Connectivity Analysis during Rubber Hand Illusion—A Pilot TMS-EEG Study in a Patient with SCI
Authors: Frey Vanessa N. , Thomschewski Aljoscha , Langthaler Patrick B. , Kunz Alexander B. , Höller Yvonne , Trinka Eugen , Nardone Raffaele
Published: February 2021

Background. Bodily self-perception is an important concept for several neurological disorders, including spinal cord injury (SCI). Changing one’s bodily self-perception, e.g., via rubber hand illusion (RHI), induces alterations of bottom-up and top-down pathways and with this the connectivity between involved brain areas. We aim to examine whether (1) this process can be manipulated by changing cortical excitability, (2) connectivity between relevant brain areas differ when the RHI cannot be evoked, and (3) how this projection differs in a patient with SCI. Method. We applied RHI and facilitatory theta burst stimulation (TBS) on the right primary somatosensory cortex (S1) of 18 healthy participants and one patient with incomplete, cervical SCI. During RHI, we recorded high-density electroencephalography (HD-EEG) and extracted directed and nondirected connectivity measures. Results. There is no difference in connectivity between sham and real TBS or in the effectivity of RHI. We observed a higher laterality in the patient, i.e., higher connectivity of the right and lower of the left hemisphere. Besides this, connectivity patterns do not differ between healthy participants and the patient. Conclusion. This connectivity pattern might represent a neuroplastic response in the attempt to overcome the functional impairment of the patient resulting in a similar overall connectivity pattern to the healthy participants, yet with a higher sensitivity towards RHI and a higher laterality. The cortico-cortical communication was not altered depending on whether the illusion was provoked or not; hence, the perceptory illusion could not be observed in the EEG analysis.
Path-Integral-Based Reinforcement Learning Algorithm for Goal-Directed Locomotion of Snake-Shaped Robot
Authors: Yongqiang Qi , Hailan Yang , Dan Rong , Yi Ke , Dongchen Lu , chunyang Li , Xiaoting Liu
Published: February 2021

This paper proposes a goal-directed locomotion method for a snake-shaped robot in 3D complex environment based on path-integral reinforcement learning. This method uses a model-free online Q-learning algorithm to evaluate action strategies and optimize decision-making through repeated “exploration-learning-utilization” processes to complete snake-shaped robot goal-directed locomotion in 3D complex environment. The proper locomotion control parameters such as joint angles and screw-drive velocities can be learned by path-integral reinforcement learning, and the learned parameters were successfully transferred to the snake-shaped robot. Simulation results show that the planned path can avoid all obstacles and reach the destination smoothly and swiftly.
The Validity and Reliability of the Persian Version of the Family Health Climate Scale (FHC‐Scale) in Female Students and Their Mothers in Iran 2019
Authors: Ostovarfar Jeyran , Kaveh Mohammad Hossein , Ghahramani Leila , Karimi Masoud , Asadollahi Abdolrahim , Zare Razie
Published: February 2021

Objectives. This study examined the validity and reliability of the Family Health Climate Scale (FHC‐Scale) among Iranian families. Second, can it be attributed to other family members by measuring the health climate in one person? Method. In total, 261 female students and 196 mothers completed the FHC‐Scale. The study instrument was a Persian version of the FHC‐Scale prepared through a translation and back‐translation process. Results. The results showed that the Persian version of the FHC‐Scale is acceptable. Cronbach’s alpha coefficient for FHC‐PA in female students and their mothers, respectively, was 0.88 and 0.86 for the whole scale. Cronbach’s alpha coefficient for FHC‐NU in female students and their mothers, respectively, was 0.83 and 0.92 for the whole scale. The CVI values for all the items were equal to or above 0.8, and the CVR value for the total scale was 0.90. Conclusion. The Persian version of the FHC‐Scale is therefore an effective tool for evaluating the different dimensions of family health climate in the Iranian population.
APOBEC and Cancer Viroimmunotherapy: Thinking the Unthinkable
Authors: Vile Richard G. , Melcher Alan , Pandha Hardev , Harrington Kevin J. , Pulido Jose S.
Published: February 2021

The apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) family protects against infection by degrading incoming viral genomes through cytosine deamination. Here, we review how the potential to unleash these potent DNA mutagens comes at a price as APOBEC DNA mutagenesis can contribute to development of multiple types of cancer. In addition, because viral infection induces its expression, APOBEC is seen as the enemy of oncolytic virotherapy through mutation of the viral genome and by generating virotherapy-resistant tumors. Therefore, overall APOBEC in cancer has received very poor press. However, we also speculate how there may be silver linings to the storm clouds (kataegis) associated with APOBEC activity. Thus, although mutagenic genomic chaos promotes emergence of ever more aggressive subclones, it also provides significant opportunity for cytotoxic and immune therapies. In particular, the superpower of cancer immunotherapy derives in part from mutation, wherein generation of tumor neoantigens—neoantigenesis—exposes tumor cells to functional T-cell repertoires, and susceptibility to immune checkpoint blockade. Moreover, APOBECs may be able to induce suprathreshold levels of cellular mutation leading to mitotic catastrophe and direct tumor cell killing. Finally, we discuss the possibility that linking predictable APOBEC-induced mutation with escape from specific frontline therapies could identify mutated molecules/pathways that can be targeted with small molecules and/or immunotherapies in a Trap and Ambush strategy. Together, these considerations lead to the counterintuitive hypothesis that, instead of attempting to expunge and excoriate APOBEC activity in cancer therapy, it might be exploited—and even, counterintuitively, encouraged.
Nutcracker Syndrome: A Single-Center Experience
Authors: Pardinhas Clara , do Carmo Carmén , Gomes Clara , Escada Luís , Alves Rui
Published: February 2021

Nutcracker syndrome, whose prevalence and natural history are still poorly known, is a clinical syndrome caused by left renal vein compression between the superior mesenteric artery and the aorta. Long-term results and treatment outcomes are not well known. Our group aimed to characterize 7 patients diagnosed with nutcracker syndrome in childhood and to describe their clinical manifestations, diagnostic approaches, and mostly their clinical evolution, rate of complications, and treatment outcomes.
Endothelium-Specific GTP Cyclohydrolase I Overexpression Restores Endothelial Function in Aged Mice
Authors: Yan Lang , Zhang Ji-qian-zhu , Dai Xiao-yu , Li Jin-feng , Gao Fang-yuan , Zhang Xiao-fang , Tian Yi-jun , Shi Wen-jing , Zhu Jiang-bo , Chen Ji-kuai
Published: February 2021

This study tested the hypothesis that endothelium-specific GTP cyclohydrolase I (GTPCH I) overexpression (Tg-GCH) restores age-associated endothelial dysfunction in vivo. Aortic GTPCH I expression and serum nitric oxide (NO) release were measured in young and aged mice. Aortic rings from young and aged wild-type (WT) mice and aged Tg-GCH mice were suspended for isometric tension recording. A hind limb ischemia model was used to measure blood flow recovery. Aged mice showed reduced GTPCH I expression in the aorta and decreased NO levels in serum. Compared with aged WT mice, Tg-GCH significantly elevated NO levels in serum in aged Tg-GCH mice, restored the impaired aortic relaxation in response to acetylcholine, and significantly elevated aortic constriction in response to L-NAME. Importantly, aged Tg-GCH mice displayed a significant increase in blood flow recovery compared with aged WT mice. GTPCH I reduction contributes to aging-associated endothelial dysfunction, which can be retarded by Tg-GCH.
Implementing Videoconference CBT for Depression in Routine Outpatient Care: Outcome, Working Alliance, and Influence of Patients’ Technology Commitment
Authors: Voderholzer Ulrich , Beintner Ina , Backes Bernhard , Esguerra Elisa , Hessler-Kaufmann Johannes Baltasar
Published: February 2021

Background: While videoconference cognitive behavioral therapy (V-CBT) has shown promising results in controlled studies, data from routine care are rare. We examined (1) changes in depressive symptoms and life satisfaction during V-CBT in German routine outpatient care for patients with depressive disorders, (2) the quality of the established working alliance, and (3) the influence of working alliance and the patients’ technology commitment on outcomes. Patients and Methods: Patients with primary diagnoses of depressive disorders were treated with V-CBT and concurrent internet-guided self-help via the MindDoc program, which operates within the regulations of the German health care system. The patients completed the 9-item Patient Health Questionnaire (PHQ-9) for depressive symptoms, an item on life satisfaction before and after treatment, the Working Alliance Inventory (WAI), and the Technology Commitment questionnaire for beliefs about handling technology. Results: Fifty-nine patients (71.2% female) with a mean age of 44.46 years (SD = 12.86) were included in the analyses. Longitudinal multilevel mixed models revealed improvements in depressive symptoms (Cohen’s d = 1.27) and life satisfaction (d = 0.80). The working alliance was good and showed a positive association with outcome, while technology commitment did not. Conclusion: V-CBT seems effective in reducing depressive symptoms, increasing life satisfaction, and establishing a good working alliance in routine care.
Esclerosis sistémica: Reconocimiento del valor pronóstico de las pruebas de ejercicio cardiopulmonar
Authors: Krüger Stefan
Published: February 2021

Background: Systemic sclerosis (SSc) is a severe rheumatic disease of the interstitial tissue, in which heart and lung involvement can lead to disease-specific mortality. Our study tests the hypothesis that in addition to established prognostic factors, cardiopulmonary exercise testing (CPET) parameters, particularly peak oxygen uptake (peakVO2) and ventilation/carbon dioxide (VE/VCO2)-slope, can predict survival in patients with SSc. Subjects and methods: We retrospectively assessed 210 patients (80.9% female) in 6 centres over 10 years with pulmonary testing and CPET. Survival was analysed with Cox regression analysis (adjusted for age and gender) by age, comorbidity (Charlson-Index), body weight, body-mass index, extensive interstitial lung disease, pulmonary artery pressure (measured by echocardiography and invasively), and haemodynamic, pulmonary and CPET parameters. Results: Five- and ten-year survival of SSc patients was 93.8 and 86.9%, respectively. There was no difference in survival between patients with diffuse (dcSSc) and limited cutaneous manifestation (lcSSc; p = 0.3). Pulmonary and CPET parameters were significantly impaired. Prognosis was worst for patients with pulmonary hypertension (p = 0.007), 6-min walking distance < 413m (p = 0.003), peakVO2 < 15.6 mL•kg− 1•min− 1, and VE/VCO2-slope > 35. Age (hazard ratio HR = 1.23; 95% confidence interval CI: 1.14;1.41), VE/VCO2-slope (HR = 0.9; CI 0.82;0.98), diffusion capacity (Krogh factor, HR = 0.92; CI 0.86;0.98), forced vital capacity (FVC, HR = 0.91; CI 0.86;0.96), and peakVO2 (HR = 0.87; CI 0.81;0.94) were significantly linked to survival in multivariate analyses (Harrell’s C = 0.95). Summary: This is the first large study with SSc patients that demonstrates the prognostic value of peakVO2 <15.6 mL•kg− 1•min− 1 (< 64.5% of predicted peakVO2) and VE/VCO2-slope > 35.
Em direção a um professor com autoridade: razões e modalidades
Authors: Diodato Francesco
Published: February 2021

O presente artigo pretende lançar luz sobre algumas práticas que permitem ao professor expressar melhor as potencialidades de cada aluno. Após a apresentação de algumas possíveis causas que levam certos alunos a comportar-se de forma pouco edificante, o trabalho segue com uma exposição das razões que deveriam incentivar os professores a preferir um estilo educativo autorizante, a um estilo autoritário, permissivo e mesmo democrático, e uma definição de professor amoroso. O artigo traz, ainda, considerações sobre a técnica do convencimento racional, sobre o ambiente de aprendizagem, sobre a figura do estudante-pesquisador e sobre o sistema de recompensase punições, a ser substituído preferencialmente pelo sistema de consequências. Foram inseridas no trabalho, várias vezes, sugestões que provêm das neurociências. Em particular, reflete-se sobre a atenção que o professor deveria reservar à amídala dos alunos, uma vez que desempenha um papel importante nas emoções: uma consideração inadequada poderia induzir o aluno até a recusar-se a aprender com um determinado professor. Abordou-se, ainda, o discurso da peculiaridade do cérebro do adolescente, válido também, como no caso do escritor, quando se trata de estudantes universitários, porque, biologicamente, o cérebro, mesmo naquela idade, ainda não está maduro.
Percutaneous Implantation of Adult Sized Stents for Coarctation of the Aorta in Children ≤20 kg
Authors: Boe Brian A. , Armstrong Aimee K. , Janse Sarah A. , Loccoh Eméfah C. , Stockmaster Katie , Holzer Ralf J. , Cheatham Sharon L. , Cheatham John P. , Berman Darren P.
Published: February 2021

Background:

Stent implantation (SI) is more effective than balloon angioplasty for the treatment of coarctation of the aorta (CoA). Due to technical factors, balloon angioplasty is more commonly performed in small patients. We sought to evaluate outcomes of percutaneous adult sized SI for the treatment of CoA in small patients.

Methods:

A single-center retrospective review of all patients ≤20 kg who underwent percutaneous adult sized SI for native or recurrent CoA from 2004 to 2015 was performed.

Results:

Thirty-nine patients (20 patients ≤10 kg) were identified, with 28 (71.8%) having recurrent CoA and 22 (56.4%) previously failed balloon angioplasty. At the time of SI, the median (range) patient age and weight were 1.1 (0.3–7.9) years and 10 (5.5–20.4) kg, respectively. SI resulted in significant improvements in the median gradient (26 mm Hg [interquartile range (IQR), 18–42] to 0 mm Hg [IQR, 0–2];
P
< 0.05) and median minimum diameter (3.6 mm [IQR, 2.4–4.8] to 7.7 mm [IQR, 6.5–9.4];
P
<0.05). Seven patients (18%) had procedural adverse events. Twenty-seven (69%) patients underwent elective reintervention at a median time of 49.3 (IQR, 26.5–63.2) months from SI, with 8 (21%) stents requiring repeat SI for stent fracture. Over a median follow-up of 67.2 (IQR, 33.8–116.1) months, 25 patients (69%) were without hypertension or blood pressure gradient. Three (11%) patients developed femoral arterial occlusion.

Conclusions:

Adult sized SI is an alternative to surgical intervention for small patients with CoA. SI carries a risk of access-related complications, which may improve with the development of lower profile stents with adult sized maximum diameters.
Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease
Authors: Ye Nan , Jardine Meg J. , Oshima Megumi , Hockham Carinna , Heerspink Hiddo J.L. , Agarwal Rajiv , Bakris George , Schutte Aletta E. , Arnott Clare , Chang Tara I. , Górriz Jose L. , Cannon Christopher P. , Charytan David M. , de Zeeuw Dick , Levin Adeera , Mahaffey Kenneth W. , Neal Bruce , Pollock Carol , Wheeler David C. , Luca Di Tanna Gian , Cheng Hong , Perkovic Vlado , Neuen Brendon L.
Published: February 2021

Background:

People with type 2 diabetes and chronic kidney disease experience a high burden of hypertension, but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population are uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP-lowering therapy is also unknown.

Methods:

The CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) randomized people with type 2 diabetes and chronic kidney disease to canagliflozin or placebo. In a post hoc analysis, we investigated the effect of canagliflozin on systolic BP across subgroups defined by baseline systolic BP, number of BP-lowering drug classes, and history of apparent treatment-resistant hypertension (BP ≥130/80 mm Hg while receiving ≥3 classes of BP-lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups.

Results:

The trial included 4401 participants, of whom 3361 (76.4%) had baseline systolic BP ≥130 mm Hg, and 1371 (31.2%) had resistant hypertension. By week 3, canagliflozin reduced systolic BP by 3.50 mm Hg (95% CI, –4.27 to –2.72), an effect maintained over the duration of the trial, with similar reductions across BP and BP-lowering therapy subgroups (all
P
interaction ≥0.05). Canagliflozin also reduced the need for initiation of additional BP-lowering agents during the trial (hazard ratio, 0.68 [95% CI, 0.61–0.75]). The effect of canagliflozin on kidney failure, doubling of serum creatinine, or death caused by kidney or cardiovascular disease (hazard ratio, 0.70 [95% CI, 0.59–0.82]) was consistent across BP and BP-lowering therapy subgroups (all
P
interaction ≥0.35), as were effects on other key kidney, cardiovascular, and safety outcomes.

Conclusions:

In people with type 2 diabetes and chronic kidney disease, canagliflozin lowers systolic BP across all BP-defined subgroups and reduces the need for additional BP-lowering agents. These findings support use of canagliflozin for end-organ protection and as an adjunct BP-lowering therapy in people with chronic kidney disease.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02065791.
Freedom of Religion in the Workplace
Authors: Begović Nedim
Published: February 2021

The article analyses the case law of the European Court of Human Rights on accommodation of Islamic observances in the workplace. The author argues that the Court has not hitherto provided adequate incentives to the states party to the European Convention on Human Rights to accommodate the religious needs of Muslim employees in the workplace. Given this finding, the author proposes that the accommodation of Islam in the workplace should, as a matter of priority, be provided within a national legal framework. In Bosnia and Herzegovina, this could be achieved through an instrument of contracting agreement between the state and the Islamic Community in Bosnia and Herzegovina.
Hurricane Risk Perceptions and Evacuation Decision-Making in the Age of COVID-19
Authors: Collins Jennifer , Polen Amy , McSweeney Killian , Colón-Burgos Delián , Jernigan Isabelle
Published: February 2021

The COVID-19 pandemic increases the complexity of planning for hurricanes as social distancing is in direct conflict with human mobility and congregation. COVID-19 presents not only urgent challenges for this hurricane season due to the likeliness of continued or heightened COVID-19 threat, but also challenges with the next hurricane season with additional waves of the pandemic. There is severe urgency to understand the impact of COVID-19 risk perceptions and the extent people are willing to risk their lives by sheltering in place rather than evacuating during severe hurricanes. In June 2020, a survey (in both English and Spanish) of 40 questions was disseminated through regional planning councils, emergency management, and the media to Florida residents. A total of 7,072 people responded from over 50 counties. Most data obtained were ordinal or categorical in nature, encouraging usage of nonparametric analysis and chi-square tests. Almost half the respondents view themselves as vulnerable to COVID-19 due to preexisting health conditions, and 74.3% of individuals viewed the risk of being in a shelter during the COVID-19 pandemic as more dangerous than enduring hurricane hazards. Additionally, there was a significant number of individuals who would choose to not utilize a public shelter during COVID-19 when they would have previously. Officials can use the results of this study regarding how household evacuation plans change with social distancing to better inform strategies of shelter preparedness and COVID-19 risk mitigation to minimize risk to those in harm’s way of storm surge and other hurricane effects during a mandatory evacuation order.
Impact of Urbanization on the Nature of Precipitation at Toronto, Ontario, Canada
Authors: Gough William A.
Published: February 2021

A newly developed precipitation phase metric is used to detect the impact of urbanization on the nature of precipitation at Toronto, Ontario, Canada, by contrasting the relative amounts of rain and snow. A total of 162 years of observed precipitation data were analyzed to classify the nature of winter-season precipitation for the city of Toronto. In addition, shorter records were examined for nearby climate stations in less-urbanized areas in and near Toronto. For Toronto, all winters from 1849 to 2010 as well as three climate normal periods (1961–90, 1971–2000, and 1981–2010) were thus categorized for the Toronto climate record. The results show that Toronto winters have become increasingly “rainy” across these time periods in a statistically significant fashion, consistent with a warming climate. Toronto was compared with the other less urban sites to tease out the impacts of the urban heat island from larger-scale warming. This yielded an estimate of 19%–27% of the Toronto shift in precipitation type (from snow to rain) that can be attributed to urbanization for coincident time periods. Other regions characterized by similar climates and urbanization with temperatures near the freezing point are likely to experience similar climatic changes expressed as a change in the phase of winter-season precipitation.
Diapycnal Mixing in the Subthermocline of the Mariana Ridge from High-Resolution Seismic Images
Authors: Tang Qunshu , Jing Zhiyou , Lin Jianmin , Sun Jie
Published: February 2021

The Mariana Ridge is one of the prominent mixing hotspots of the open ocean. The high-resolution underway marine seismic reflection technique provides an improved understanding of the spatiotemporal continuous map of ocean turbulent mixing. Using this novel technique, this study quantifies the diapycnal diffusivity of the subthermocline (300–1200-m depth) turbulence around the Mariana Ridge. The autotracked wave fields on seismic images allow us to derive the dissipation rate ε and diapycnal diffusivity Kρ based on the Batchelor model, which relates the horizontal slope spectra with +1/3 slope to the inertial convective turbulence regime. Diffusivity is locally intensified around the seamounts exceeding 10−3 m2 s−1 and gradually decreases to 10−5–10−4 m2 s−1 in ~60-km range, a distance that may be associated with the internal tide beam emanating paths. The overall pattern suggests a large portion of the energy dissipates locally and a significant portion dissipates in the far field. Empirical diffusivity models Kρ(x) and Kρ(z), varying with the distance from seamounts and the height above seafloor, respectively, are constructed for potential use in ocean model parameterization. Geographic distributions of both the vertically averaged dissipation rate and diffusivity show tight relationships with the topography. Additionally, a strong agreement of the dissipation results between seismic observation and numerical simulation is found for the first time. Such an agreement confirms the suitability of the seismic method in turbulence quantification and suggests the energy cascade from large-scale tides to small-scale turbulence via possible mechanisms of local direct tidal dissipation, near-local wave–wave interactions, and far-field radiating and breaking.
Thematic Collages in Participatory Photography: A Process for Understanding the Adoption of Zero Budget Natural Farming in India
Authors: Walker Grady , Osbahr Henny , Cardey Sarah
Published: February 2021

This paper presents the use of thematic collages as a methodological innovation to participatory photography as a research framework. Participatory photography was used to understand the subjective “off-script” motivations behind the full or partial adoption of Zero Budget Natural Farming (ZBNF) by members of women’s self-help groups in Andhra Pradesh, India. The addition of thematic collages to existing participatory photography methods was developed as a mechanism to better support the dialogic generation of new Freirean “generative themes” for investigation by a group. Further, the use of thematic collages invites the integration of “renegade” or non-thematic images into participant group analysis. ZBNF is an agricultural practice that has become an extension priority in Andhra Pradesh. It emphasizes the use of defined chemical-free inputs and regenerative farming techniques as a holistic approach toward socio-ecological resilience. As part of an interdisciplinary research project, this participatory photography design was piloted parallel to a soil science experiment in three geographically distinct agroecological zones in Andhra Pradesh. We show how participatory photography, with the novel addition of thematic collages, can be integrated into interdisciplinary research as a method to discover the underlying motivations to adopt agricultural practices and participate in agricultural movements like Zero Budget Natural Farming.
Metformin Upregulates Mir-26a to Improve Erythropoiesis in Preclinical Models of Diamond Blackfan Anemia through Suppression of Nlk Expression
Authors: Wilkes Mark C , Siva Kavitha , Mercado Jacqueline D , Wentworth Ethan Patrick , Saxena Mallika , Chen Jun , Narla Anupama , Glader Bertil , Lin Shuo , Serrano Manuel , Flygare Johan , Sakamoto Kathleen M.
Published: February 2021

Nemo-like Kinase (NLK) is an atypical member of the Mitogen-activated protein (MAP) kinase family and shares a highly conserved kinase domain with other MAP kinases. For this reason it is challenging to design small molecules that specifically inhibit NLK. In hematopoiesis, NLK expression is suppressed in all lineages except erythroid progenitors. In non-erythroid progenitors, micro-ribonucleic acid (miR)-181 is upregulated and binds to the 3' untranslated region (UTR) of NLK transcripts, resulting in dramatic degradation of NLK transcripts.

NLK is not activated or required for healthy erythropoiesis, but in Diamond Blackfan Anemia (DBA), NLK is chronically hyper-activated, which contributes to failed erythroid expansion and disease pathogenesis. Given the sensitivity of NLK transcripts to 3'UTR binding-mediated degradation, we hypothesized that targeting NLK degradation by upregulating miRNAs that bind the NLK 3'-UTR could provide an alternative approach to directly inhibiting the kinase to suppress aberrant NLK activity in bone marrow progenitors from DBA patients.

One miRNA binding site that is present in the NLK-3'UTR is miR-26a. We determined that miR-26a is upregulated 2.4-fold (p=0.009) in CD235+ erythrocytes by the Type 2 diabetes drug metformin. Metformin suppressed NLK expression 62.4% (p=0.006) and improved erythroid expansion 4-fold (p=0.001) in human and 6-fold (p=0.042) in zebrafish models of DBA. This effect required an intact miR-26a binding site within the NLK 3'UTR. However, metformin failed to induce miR-26a in murine models of DBA, however the exogenous expression of miR-26a suppressed NLK 36.4% (p=0.028) and improved erythropoiesis 2-fold (p=0.017).

In summary, targeted suppression of NLK through metformin-mediated upregulation of NLK transcript-binding miRNAs effectively improved red blood cell production from 5.6% up to 33.3% of controls in a preclinical model of DBA. These results suggest that metformin is a potential drug for treatment of DBA.

Disclosures

Glader: Agios Pharmaceuticals, Inc.: Consultancy.

OffLabel Disclosure:

metformin. This drug is given to differentiating HSPCs in vitro to examine effect on specific kinases.
Level of Scientific Evidence Underlying Recommendations from the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Hematologic Malignancies: Are We Moving Forward?
Authors: Desai Aakash , Fuentes Harry E , Tella Sri Harsha , Scheckel Caleb J , Poonacha Thejaswi , Go Ronald S.
Published: February 2021

Background: National Comprehensive Cancer Network (NCCN) guidelines are the most comprehensive and widely used standard for clinical care in malignant hematology by clinicians and payers in the US. The level of scientific evidence in NCCN guidelines for malignant hematological conditions has not been recently investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common hematologic malignancies with regard to recommendations for staging, initial and salvage therapy, and surveillance.

Methods: NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are: category I, high level of evidence such as randomized controlled trials with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. We compared our results with previously published results from 2011 guidelines.

Results: Total recommendations increased by 16.6% from 1160 (2011) to 1353 (2020). Of the 1353 recommendations, Category 1, 2A, 2B and 3 EC were 5%, 91%, 4%, 1% while in 2011 they were 3%, 93%, 4% and 0% respectively. Recommendations with category 1 EC were found in all guidelines, except for Burkitt's Lymphoma. 6.3% of therapeutic recommendations were category 1 EC with the majority (56.4%) pertaining to initial therapy. Guidelines with highest proportions of therapeutic recommendations with category 1 EC were Multiple Myeloma (12.4%), CLL/SLL (6.9%) and AML (5.6%). Between 2011 and 2020, the proportion of category I recommendations increased significantly only in Follicular lymphoma and CLL/SLL. No category 1 EC recommendations existed in staging or surveillance.

Conclusion: Recommendations issued in the 2020 NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. Despite the major advances in hematology in the past decade, this is largely unchanged. Our study underscores the urgent need and available opportunities to expand the current evidence base in malignant hematological disorders which forms the platform for clinical practice guidelines.

Figure

Disclosures

No relevant conflicts of interest to declare.
This Is a Title: Cytarabine Combined with PD-1 Inhibitor in the Treatment of R/R-AML: A Report of 3 Cases and Literature Review
Authors: Wang Yu , Jiang Chuanyan , Yang Xi , Dai Jingying , Zou Mengying , Wang Yijing , Wang Jun , Wu Jiafei , LI Hui
Published: February 2021

Objectives: To explore the efficacy and safety of high-dose cytarabine combined with PD-1 inhibitors and demethylation drugs in relapsed and refractory acute myeloid leukemia (R/R-AML) in Chinaand to investigatethe dynamic changes of Treg cells, CD4+ T cells, CD8+ T cells, TNF-α, INF-γ, and IL-6 in the prognosis of the disease.

Methods:A total of three patients with R/R-AML treated in our department were included in the study. None of the three patients had received at least two courses of standard chemotherapy before and did not obtain remission.The cellular immunity and cytokines were evaluated on the 1st, 8th, 15th, and 22nd day of the treatment.In the study,eligible R/ R-AML patients (n=3) were treated with azacytidine 75mg/m2 d1-d7, cytarabine 2g/m2 d1-d5, PD-1 inhibitor 200mg d1、d14.The efficacy were evaluated by CR, PR, ORR, PFS, OS, and ED. The safety were evaluated by hematological and non-hematological toxicity.

Results: Among the three patients, one patient achieved CR, and one patient achieved PR. The patient who achieved CR successfully underwent allo-HSCT. One patient did not achieve remission and died of disease progression. Three patients were well tolerated to chemotherapy, and non-hematological toxicity was mainly respiratory tract infection, gastrointestinal reaction, and liver function damage.At present, no immune-related tissue injury was observed. Grade III-IV hematologic toxicity was the major adverse reaction, and the longest duration of agranulocytosis was 22 days.The proportion of Treg cells decreased, and the proportion of CD4+ T cells and CD8+ T lymphocytes increased in 2 patients after treatment. One patient received CR and underwent allo-HSCT. One patient showed an increase in the proportion of Treg cells, but there was no significant dynamic change in CD4+ T lymphocytes and CD8+ T lymphocytes. INF-γ increased in 1 patient. Dynamic changes in IL-10, IL-6, and TNF-α were not observed.

Conclusions: PD-1 inhibitor combined with high dose cytarabine based chemotherapy may be a salvage treatment for R/R-AML. The dynamic changes of CD4+ T lymphocyte, CD8+ T lymphocyte, Treg cell, and INF-α may reflect the therapeutic effect in advance.

Disclosures

No relevant conflicts of interest to declare.
Adipocyte Fatty Acid Binding Protein Promotes Multiple Myeloma through Regulating Bone Marrow Microenvironment
Authors: Shu Lingling , Li Jinyuan , Wang Weida , Wu Xiaoping , Huang Hanying , Hu Fang , Liang Yang
Published: February 2021

Multiple myeloma (MM) is a plasma cell malignancy in bone marrow, which often occurs in middle-aged and elderly people and also obese patients. Aging and obesity can lead to the ectopic accumulation of adipocytes in bone marrow, which can cause the change of bone marrow microenvironment. Bone marrow adipocyte (BMA) displays distinct immune regulatory properties rather than provides energy substrates. Despite BMA accounts for 70% of the entire volume of bone marrow microenvironment, while the mechanisms still remain elusive. The present study aims to investigate the precise mechanism of BMA promoting myeloma pathogenesis and new potential therapeutic strategies targeting bone marrow microenvironment.

Newly diagnosed MM patients and their relative healthy control in our cancer center were recruited. We found that the quantity of BMA increased significantly in multiple myeloma patients, accompanied with the elevated level of adipocyte fatty acid binding protein (A-FABP) by flow cytometry and immunohistochemistry staining. A-FABP is a fatty acid chaperone, which abundantly expressed in adipocytes, playing a critical role in lipid metabolism and immune response. To further explore the role of A-FABP in the pathogenesis of MM, A-FABP knockout (KO) mice and their wide type (WT) littermates were employed and fed with stand chow or high fat diet (HFD). Tumor burden and MM-related osteolytic lesions were significantly lower in A-FABP KO mice comparing to their WT littermates fed with HFD. It was observed that A-FABP deficiency did not change the content of BMA in bone marrow, but cytokines levels in bone marrow such as TNFα, IL-6, RANKL, DPP4 were significantly reduced. The infiltration and pro-inflammatory polarization (M1/M2) of macrophages (MΦ) decreased significantly. Moreover, A-FABP promotes the expression of Th1 and Th17 cells, while the percentage of Th2 and Treg cells are significantly declined. Furthermore, pharmacological inhibition of A-FABP by administration BMS309403 also alleviates the invasion and metastasis of MM in mouse. In addition, co-culture of myeloma cells with pharmacological inhibition or genetic depletion of A-FABP in adipocytes significantly decreased the uptake of free fatty acid and oxygen consumption of myeloma cells.

In conclusion, A-FABP increased in BMA in response to aging or obesity, remodeled the energy and lipid metabolism of myeloma cells, and manipulated bone marrow microenvironment to a pro-tumor environment, promoting the proliferation and migration of myeloma cells. This study will shed light on the potential of A-FABP specific inhibitor BMS309403 as the therapeutic strategy of multiple myeloma targeting bone marrow microenvironment.

Disclosures

No relevant conflicts of interest to declare.
Association of Anticoagulant Use with COVID-19 Diagnosis
Authors: Kavecansky Juraj , Dusendang Jennifer R , Tavakoli Jahan , Schmittdiel Julie , Ho Gwendolyn , Loyles Jodi , Pai Ashok
Published: February 2021

Background

The Coronavirus Disease 2019 (COVID-19) pandemic has challenged anticoagulation providers with providing optimal care while minimizing exposure risk, specifically in the management of patients on chronic warfarin. Here we provide data regarding our experience with managing patients on chronic anticoagulants, including warfarin, within Kaiser Permanente Northern California (KPNC), a large integrated healthcare delivery system serving more than 4 million patients.

Aim

To identify whether being on anticoagulation or antiplatelet agents correlates with an increased risk of contracting COVID-19.

Methods

We identified patients within KPNC electronic medical records on either warfarin, direct oral anticoagulation (DOAC) and/or antiplatelet agents between February 25 and July 3, 2020, as well as a randomly identified control group of patients not taking anticoagulation or antiplatelet. We looked for a correlation between taking anticoagulation and antiplatelets with the risk of testing positive for COVID-19.

Results/Conclusions

Among 188,438 patients on chronic anticoagulants or antiplatelets and 188,438 controls, 1,029 patients tested positive for COVID-19 during the study period. Being on chronic anticoagulants or antiplatelets was not associated with increased risk for a positive test. Patients on warfarin (N=30,242) also had no increased risk of developing COVID-19 compared to patients not on anticoagulation or antiplatelet therapy (odds ratio 0.87, 95% confidence interval 0.64-1.17). The time in the therapeutic range (TTR) of patients on warfarin during the COVID-19 pandemic remained near 72%, consistent with prior TTR, demonstrating persistent efficacy of anticoagulation despite measures to reduce COVID-19 transmission. Our data demonstrates the safety of continuing chronic warfarin in patients during the COVID-19 pandemic.

Disclosures

No relevant conflicts of interest to declare.