bluuebunny/crossref_metadata_2025 huggingface dataset:
Postcolonial world literature: Narration, translation, imagination
Authors: Wiemann Dirk , Mazumdar Shaswati , Raja Ira
Published: February 2021

Postcolonial criticism has repeatedly debunked the ostensible neutrality of the ‘world’ of world literature by pointing out that and how the contemporary world – whether conceived in terms of cosmopolitan conviviality or neoliberal globalization – cannot be understood without recourse to the worldly event of Europe’s colonial expansion. While we deem this critical perspective indispensable, we simultaneously maintain that to reduce ‘the world’ to the world-making impact of capital, colonialism, and patriarchy paints an overly deterministic picture that runs the risk of unwittingly reproducing precisely that dominant ‘oneworldness’ that it aims to critique. Moreover, the mere potentiality of alternative modes of world-making tends to disappear in such a perspective so that the only remaining option to think beyond oneworldness resides in the singularity claim. This insistence on singularity, however, leaves the relatedness of the single units massively underdetermined or denies it altogether. By contrast, we locate world literature in the conflicted space between the imperial imposition of a hierarchically stratified world (to which, as hegemonic forces tell us, ‘there is no alternative’) and the unrealized ‘undivided world’ that multiple minor cosmopolitan projects yet have to win. It is precisely the tension between these ‘two worlds’ that brings into view the crucial centrality not of the nodes in their alleged singularity but their specific relatedness to each other, that both impedes and energizes world literature today and renders it ineluctably postcolonial.
Migrant Allies and Sexual Remittances: How International Students Change the Sexual Attitudes of Those Who Remain Behind
Authors: Wang Skyler
Published: February 2021

How does moving from a sexually conservative country to a liberal one alter the way international students think about homosexuality and same-sex rights, and how does this impact their communities back home? Drawing on survey data with 90 heterosexual Singaporean students studying at the University of British Columbia in Vancouver, as well as interview data with 17 students and 14 of their family members and friends who remained in Singapore, this study finds that despite having a broad spectrum of prior opinions, the majority of the student participants acquired increasingly accepting sexual attitudes after their relocation. Furthermore, many of them send these new conceptions as “sexual remittances” to their originating communities, changing the values of those who remain behind. This study helps lay the groundwork for further investigations of how engagements among international students and their social networks can contribute to evolving understandings of transnational sexuality and the globalization of culture.
Process development options for electronic waste fractionation to achieve maximum material value recovery
Authors: Bruch Johannes-Robert , Bokelmann Katrin , Grimes Sue M
Published: February 2021

Revised legislation and bans on imports of waste electrical and electronic equipment (WEEE) into many Asian countries for treatment are driving the need for more efficient WEEE fractionation in Europe by expanding the capacity of treatment plants and improving the percentage recovery of materials of economic value. Data from a key stakeholder survey and consultation are combined with the results of a detailed literature survey to provide weighted matrix input into multi-criteria decision analysis calculations to carry out the following tasks: (a) assess the relative importance of 12 process options against the 6 industry-derived in-process economic potential criteria, that is, increase in product quality, increase in recycling rate, increase in process capacity, decrease in labour costs, decrease in energy costs and decrease in disposal costs; and (b) rank 25 key technologies that have been selected as being the most likely to benefit the efficient sorting of WEEE. The results indicate that the first stage in the development of any total system to achieve maximum economic recovery of materials from WEEE has to be the selection and application of appropriate fractionation process technologies to concentrate valuable components such as critical metals into the smallest possible fractions to achieve their recovery while minimising the disposal costs of low-value products. The stakeholder-based study has determined the priority for viable technical process developments for efficient WEEE fractionation and highlighted the economic and technical improvements that have to be made in the treatment of WEEE.
Representations of refugees in their home countries and abroad: A content analysis of la caravana migrante/the migrant caravan in Central America and the United States
Authors: Kenix Linda Jean , Lopez Jorge Bolanos
Published: February 2021

In October 2018, Honduran citizens started walking toward the American South border looking to be allowed entry into the United States due to not having work opportunities nor humanitarian aid in Honduras. More people joined them and this group was named la caravana migrante, the migrant caravan. Our content analyses of articles in five U.S. and five Central American newspapers sought to find similarities and differences in reporting. Despite differences in language and proximity to the caravan, reporting showed strong uniformity both within and across countries. Implications for universal norms of journalism as well as intermedia agenda setting were explored.
Within Group Ethnic Diversity in Latinx Psychological Research: A Publication Analysis
Authors: Mendez Luis O. , Cortina Kai S.
Published: February 2021

Based on a population-representation approach using census data we explored the breadth of research in the Journal of Latinx Psychology ( N = 154) and Hispanic Journal of Behavioral Sciences ( N = 94) with respect to distribution across states and nationality background of the Latinx’ samples. Over 90% of the empirical studies are based on Latinx samples within the US. Out of those, only 60% provided information specific enough to identify the ethnic background of the sample beyond Hispanic/Latinx or other vague descriptors (e.g., “multiethnic”). With 80% of the samples, Mexicans are overrepresented compared to the population statistics of (documented) Latinx in the US. Findings also reveal an overrepresentation of the Southwest region compared to the overall distribution of Latinx across the US. It is suggested that Latinx journals take a more active role in fostering publications of Latinx subpopulations which are often clustered in regions other than the Southwest.
Determination of vehicle requirements of AGV system based on discrete event simulation and response surface methodology
Authors: Fu Jianlin , Zhang Jian , Ding Guofu , Qin Shengfeng , Jiang Haifan
Published: February 2021

The determination of AGV vehicle requirements in a manufacturing system has a great impact on the system performance. This paper first defines the AGV vehicle requirement determination as a general optimization problem, and secondly develops a new AGV vehicle requirement determination method capable of effective solving the problem. This method features with the combination of discrete event simulation (DES), sensitivity analysis, fractional factorial design (FFD) and response surface methodology (RSM). Tests and comparisons with other simulation based methods have shown that the proposed method combining the simulation method with analytical method, can make full use of their respective advantages and overcome the defects of existing methods. It is more practical.
Effect of micro double helical grooved tools on performance of electric discharge drilling of Ti-6Al-4V
Authors: Jacob Krupa Serah , Samuel G.L.
Published: February 2021

Machining of complex features and holes on superalloys is a topic of both industrial and academic interest. Though the demand for high aspect ratio holes on Ti-6Al-4V is high in aerospace, biomedical and chemical industries, machining the same is very challenging due to the low thermal conductivity and debris accumulation in the machining zone. The present-day methods of hole drilling by unconventional methods like Electric Discharge Machining (EDM) make use of electrodes with poor flushing capabilities. Hence the motivation of the present work is to develop a method to modify the geometry of Electric Discharge Drilling (EDD) tools in order to enhance debris removal. For the first time an attempt has been made to machine micro double-helical grooves on EDD tools in a single pass. Solid, single-helical and double-helical electrodes are developed and through-holes are drilled on a Ti-6Al-4V workpiece. A comparative analysis of the performance of these three types of tools with respect to the machining time, electrode wear rate and hole quality is carried out. From Computational Fluid Dynamics (CFD) simulations it is seen that the double-helical grooved tool is superior in debris removal. The best values of the machining time of 183.33 s, overcut of 2.19 mm, hole taper angle of 7.93° and area of recast layer of 6.66 mm2 are obtained on the holes machined using double-helical electrodes. The mentioned tool has the potential to overcome the problem of debris removal in high aspect ratio hole drilling and surpass the present-day electric discharge drilling tools.
A model free controller based on reinforcement learning for active steering system with uncertainties
Authors: Zhao Jintao , Cheng Shuo , Li Liang , Li Mingcong , Zhang Zhihuang
Published: February 2021

Vehicle steering control is crucial to autonomous vehicles. However, unknown parameters and uncertainties of vehicle steering systems bring a great challenge to its control performance, which needs to be tackled urgently. Therefore, this paper proposes a novel model free controller based on reinforcement learning for active steering system with unknown parameters. The model of the active steering system and the Brushless Direct Current (BLDC) motor is built to construct a virtual object in simulations. The agent based on Deep Deterministic Policy Gradient (DDPG) algorithm is built, including actor network and critic network. The rewards from environment are designed to improve the effectiveness of agent. Simulations and testbench experiments are implemented to train the agent and verify the effectiveness of the controller. Results show that the proposed algorithm can acquire the network parameters and achieve effective control performance without any prior knowledges or models. The proposed agent can adapt to different vehicles or active steering systems easily and effectively with only retraining of the network parameters.
Adaptive type-2 fuzzy sliding mode control of steer-by-wire systems with event-triggered communication
Authors: Ma Bingxin , Wang Yongfu
Published: February 2021

The steering-by-wire (SbW) system is one of the main subsystems of automatic vehicles, realizing the steering control of autonomous vehicles. This paper proposes an event-triggered adaptive sliding mode control for the SbW system subject to the uncertain nonlinearity, time-varying disturbance, and limited communication resources. Firstly, an event-triggered nested adaptive sliding mode control is proposed for SbW systems. The uncertain nonlinearity is approximated by the interval type-2 fuzzy logic system (IT2 FLS). The time-varying disturbance, modeling error, and event-triggering error can be offset by robust terms of sliding mode control. The key advantage is that the high-frequency switching of sliding mode control only appears on the time derivate of control input without increasing the input-output relative degree of closed-loop SbW systems, such that the chattering phenomenon can be eliminated. Finally, theoretical analysis shows that the practical finite-time stability of the closed-loop SbW system can be achieved, and communication resources in the controller-to-actuator channels can be saved while avoiding the Zeno-behavior. Numerical simulations and experiments are given to evaluate the effectiveness of the proposed method.
Determining track-induced lateral thermal expansion forces on a curved railway track
Authors: Musazay Jubair A , Zarembski Allan M , Palese Joseph W
Published: February 2021

This research studies the development of lateral thermal expansion forces on a curved railway track. The geometric alignment of a railway right of way often requires railway tracks to be curved. This curvature which is usually defined by the radius of curvature or degree of curvature represents a higher level of complexity in the track’s analysis and design process. Particularly, presence of curvature on the track introduces multiple sources of force in the lateral (radial) direction, including, but not limited to, lateral thermal expansion, lateral wheel/rail forces due to centrifugal action, lateral components of vertical loads, bogie hunting and nosing effects of locomotives, and vehicle curving dynamics. Some of these forces are well understood such as centrifugal forces while some are not as well understood, such as lateral thermal expansion forces. To bridge this gap, this research studies the development of track-induced lateral thermal expansion forces on a curved railway track. In this research, the curved track is assumed to be an arbitrary arc section of a circular track and is modeled as an equivalent idealized circular ring for analysis. Owing to its importance, three analytical methods are used to include: 1) Timoshenko thermoelastic stress analysis in cylindrical coordinate system, 2) mechanics of thin wall cylinders and 3) adaptation of a variational calculus formulation method from a previous comparable study. A fourth analysis approach is also introduced using a commercially available finite element analysis package. The results of these analyses are compared through a wide range of parametric studies and are then validated by the finite element analysis. The results of this study showed that the several methods presented in this paper, could be used to approximate thermally induced expansion behavior (pre-buckling) on a curved railway track. While all three techniques are effective, the Timoshenko stress analysis method appears to be the most suitable as it is a direct method that examines the stress build up from the element level and takes into account additional material properties, such as the Poisson effect. The research resulted in a methodology for determining load transfer from thermally induced forces in curved railroad track to the fastener and supporting structure.
Opioid Literacy of Korean Americans in Rural Alabama: Addressing the Role of Social Determinants of Health
Authors: Lee Hee Yun , Choi Eun Young , Won Cho Rong , Song Jieun , Gajos Jamie M. , Kim Soo Young
Published: February 2021

Introduction:

Opioid crisis has disproportionately affected Alabamians with the highest opioid prescription rate, and it is subjected to affect Korean Americans (KA) negatively based on common predictors of opioid misuse that KA possess.

Method:

Cross-sectional data of KA in rural Alabama ( N = 230) were analyzed. Opioid literacy was assessed by the Brief Opioid Overdose Knowledge survey. Six social determinants of health factors were considered: financial status, educational attainment, English proficiency, household food insecurity, health literacy, and social contact.

Results:

Participants had limited opioid literacy ( M = 3.56, SD = 3.06). After adjusting for demographics and health covariates, higher levels of overall opioid literacy were associated with higher household income ( B = .48, p < .01), higher levels of health literacy ( B = .71, p < .01), and less frequent social contact ( B = −.40, p < .01). Significant social determinants of health predictors varied across subdomains of opioid literacy.

Discussion:

The findings suggest that culturally competent and community-level interventions are needed to increase opioid literacy in KA in rural Alabama.
Smoking and COVID-19: A Scoping Review
Authors: Haddad Chadia , Bou Malhab Sandrella , Sacre Hala , Salameh Pascale
Published: February 2021

Smoking affects a person’s overall health and damages nearly every organ of the body. Since smoking tobacco affects and damages the lungs, it increases the risk of respiratory infections and makes it easier for the coronavirus disease (COVID-19) to invade the lung tissue, causing more severe symptoms and increasing the risk of death. However, debates are still ongoing as to the effect of cigarette smoking on vulnerability to COVID-19. Some studies, where active smokers were underrepresented among patients with COVID-19, claimed that a “smoker’s paradox” may exist in COVID-19 and that smokers are protected from infection and severe complications of COVID-19. However, other studies reported the opposite trend. The objective of this study is to review the findings of epidemiological and in vitro studies about the association between smoking and the risk of contracting COVID-19, taking into account disease severity. Several epidemiological studies have found a higher smoking prevalence among COVID-19 infected patients. Also, studies had shown that people with respiratory diseases caused by tobacco use are at higher risk of developing severe COVID-19 symptoms. Studies have shown that in vitro, the acute exposure allows for more severe proximal airway epithelial disease from SARS-CoV-2 by reducing the mucosal innate immune response and the proliferation of airway basal stem cells and has implications for disease spread and severity in people exposed to cigarette smoke, with a more severe viral infection and cell death. Smoker patients with different comorbidities are at higher risk of contracting the COVID-19 virus and have a worse prognosis for the virus as well as for their comorbidities. Further investigations of the interaction between smoking and COVID-19 are warranted to accurately assess the risk of contracting COVID-19 among smokers, and the progression to mechanical ventilation or death in patients who suffer from it.
Association of yogic breathing with perceived stress and conception of strengths and difficulties in teenagers
Authors: Kanchibhotla Divya , Subramanian Saumya , Kaushik Bharti
Published: February 2021

Background:

Mental health problems are increasing at an alarming rate throughout the world, and teenagers are no exception. They experience high levels of stress in their formative years which often leads to poor social behavior. In the present study, we examine the effect of Sudarshan Kriya Yoga (SKY), a yogic breathing technique on perceived stress and social behavior of school going teenagers.

Method:

A cross-sectional survey was conducted. Teenagers who practiced SKY daily constituted the study group and teenagers who did not practice any form of yoga or meditation formed the control group. Child Perceived Stress scale (C-PSS) and Strength and Difficulty questionnaire (SDQ) were used to evaluate the mental health and social behavior of both groups.

Results:

Lower stress scores were observed among students who practiced SKY compared to their peers. A significant difference was observed between the groups with respect to emotional problems, conduct problems, peer problems, and pro-social behavior. Gender wise comparison highlighted that the females from the SKY group scored lower on emotional problems sub-scale compared to their counterparts from control group. Results also highlighted an improved peer to peer interaction among both boys and girls in the SKY group.

Conclusion:

The results indicate the practice of SKY is associated with reduced stress, improved self-awareness, and social behavior.
Camouflaging in an everyday social context: An interpersonal recall study
Authors: Cook Julia , Crane Laura , Bourne Laura , Hull Laura , Mandy William
Published: February 2021

Camouflaging is a social phenomenon operating within everyday social interactions of autistic and non-autistic people. The current study explored autistic adults’ camouflaging in an everyday social context via interpersonal process recall methodology (Kegan, 1969). A total of 17 autistic adults (8 females, 6 males and 3 agender/gender-neutral individuals) participated in a 10-min controlled social task designed to replicate a common day-to-day social situation. Participants then watched a video of their interaction with a researcher, actively identifying instances of camouflaging and discussing their experiences of camouflaging. Using thematic analysis, four themes were generated: (1) a strong desire for, yet uncertainty in, securing social acceptance and connection; (2) camouflaging, developed over time, as a means to achieve social acceptance and connection; (3) experiencing intrapersonal and interpersonal camouflaging consequences during social interactions; and (4) authentic socialising as an alternative to camouflaging. These findings are discussed with reference to the existing literature on stigma management outside the field of autism.

Lay abstract

Many autistic people report that, despite personal costs, they use strategies to hide their autistic characteristics or appear non-autistic at work, school or university, when speaking with health professionals, or while socialising with certain friends and family members. These strategies are often referred to as camouflaging. This study explores camouflaging during everyday social interactions. A total of 17 autistic adults were filmed taking part in a common everyday social situation – a conversation with a stranger. They then watched the video of this conversation with a researcher and answered questions about camouflaging. These autistic people told us that they (1) had a strong desire to socialise with and be valued by other people but, because of negative past experiences, they often felt unsure about their ability to do so; (2) used camouflaging to help them to socialise and be valued by others; (3) experienced negative consequences when camouflaging (e.g. fatigue, anxiety and difficulties in friendships); and (4) sometimes socialised in more autistic ways instead of camouflaging. This study shows us how autistic people often change their behaviour because of the way they are treated by nonautistic people and that autistic people may benefit from programmes that help them to socialise in more authentically autistic ways, but only if their autistic social behaviour is met with understanding and acceptance from non-autistic people.
Multi-objective sensor placement optimization for structural response estimation under spatially varying dynamic loading of bridges
Authors: Saleem Muhammad Mazhar , Jo Hongki
Published: February 2021

Although a lot of different types of sensors are available in the market only a limited number of sensors can be installed on a structure. Proper placement of these sensors plays a vital role in effectively achieving the objectives of a monitoring system. Sensor placement becomes especially critical in the case of bridges where the applied loading keeps on changing its location. A sensor layout that provides good quality structural response estimates for a given applied loading may not yield acceptable results for a different loading arrangement. Further, usually different types of sensors are installed on a structure e.g. strain gauges and accelerometers. These sensors measure different physical quantities having different units and orders of magnitude thus cannot be easily incorporated in a sensor placement optimization (SPO) process. So, this research work proposes a multi-objective sensor placement optimization approach that can effectively deal with different types of sensor measurements and spatially varying loading such as in the case of bridges. The proposed method employs an augmented Kalman filter (AKF) for structural response estimation and a multi-objective genetic algorithm for SPO. The AKF can effectively estimate structural response using a few heterogeneous noisy measurements while incorporating the modeling error. The effectiveness of the proposed method is demonstrated using a numerical example of a 3D truss bridge structure. The results show that the proposed multi-objective optimization method yields a sensor arrangement that remains effective against spatially varying dynamic loading.
Paternal prescription medication before conception: A retrospective cohort study of all births in Denmark 1997–2017
Authors: Wensink M.J. , Rizzi S. , Jensen T.K. , Skakkebaek N.E. , Lu Y. , Lindahl-Jacobsen R. , Eisenberg M.L.
Published: February 2021

Aim:

To study what medication fathers are being prescribed in the months preceding conception.

Methods:

A retrospective cohort study of Danish national registries, comprising all births in Denmark 1997–2017 (1.3 million births). Time trends and absolute levels of paternal prescription medication in the 6 months prior to conception were assessed. While all medications were examined ( N = 1335), we focused on the main medication groups, medications that have increased in use over time, and medications for which previous evidence exists of an effect on sperm quality.

Results:

The average number of prescriptions increased over the study period (from 0.75 prescriptions to 0.82 per birth). Polypharmacy (three or more prescriptions) increased from less than 8% to 10% of fathers. The use of pain medication, proton-pump inhibitors, selective serotonin reuptake inhibitors and some inhalants have all increased markedly over the last 20 years.

Conclusions:

Potential harm to the offspring done by paternal medication may present an increasing problem. As paternal medication exposure is increasing, examination of generational effects, such as major birth defects, is necessary.
Increase in sickness absence due to mental disorders in Finland: trends by gender, age and diagnostic group in 2005–2019
Authors: Blomgren Jenni , Perhoniemi Riku
Published: February 2021

Aims:

Mental disorders are among the key public health challenges and cause a significant share of sickness absence. The aim of this study was to examine gender and age-specific trends in sickness absence in Finland among non-retired persons aged 16–67 years during 2005–2019 by main diagnostic groups. Special focus was put on the development of sickness absence due to mental and behavioural disorders.

Methods:

Data on compensated sickness allowance days were retrieved from the database of the Social Insurance Institution of Finland, and data on the non-retired population aged 16–67 years from the database of Statistics Finland for years 2005–2019. Yearly age-standardised sickness absence rates (yearly sickness absence days per each person in the population at risk) according to diagnostic group were calculated for women and men in age groups 16–34, 35–49 and 50–67 years.

Results:

A steep increase in sickness absence due to mental disorders was observed between 2016 and 2019 in all age groups among both genders, but the increase was more prominent among women. The age group 16–34 years also showed a longer-term gradual increase. In all examined gender and age groups, the increase was mainly a consequence of an increase in sickness absence due to depression and anxiety disorders.

Conclusions:

Increase in sickness absence due to mental disorders is an early sign of threats to work ability and productivity of the working-age population. Several factors may simultaneously drive the development. The specific reasons for the recent trend need to be studied.
One globalisation or many? Risk society in the age of the Anthropocene
Authors: Chernilo Daniel
Published: February 2021

My goal in this article is to reconsider current ideas of globalisation, and of the relations between nature and society, by looking at two theoretical programmes of the past four decades. I start by reconsidering Ulrich Beck’s theory of risk society and highlight some of its core strengths and weaknesses. I then revisit more recent debates on the Anthropocene and unpack some key dimensions. There, I contend that arguments on the Anthropocene allow us to develop a more robust concept of globalisation than those currently available: an idea of globalisation that is the inescapable condition of what humans are as a species. Finally, I offer some preliminary reflections on the new stage of globalisation that seems to have started with the Covid-19 pandemic.
Anatomy of audience duplication networks: How individual characteristics differentially contribute to fragmentation in news consumption and trust
Authors: Peng Yilang , Yang Tian
Published: February 2021

While partisan selective exposure could drive audience fragmentation, other individual factors might also differentiate news diets. This study applies a method that disentangles the differential contributions of the individual characteristics to audience duplication networks. By analyzing a nationally representative survey about US adults’ media use in 2019 ( N = 12,043), we demonstrate that news fragmentation is driven by a myriad of individual factors, such as gender, race, and religiosity. Partisanship is still an important driver. We also distinguish between media exposure and media trust, showing that many cross-cutting ties in co-exposure networks disappear when media trust is considered. We conclude that audience fragmentation research should extend beyond ideological selectivity and additionally investigate how and why other individual-level preferences differentially contribute to fragmentation both in news exposure and in news trust.
Advanced robust control techniques for the stabilization of translational oscillator with rotational actuator based barge-type OFWT
Authors: Shah Syed Awais Ali , Gao Bingtuan , Ahmed Nigar , Liu Chuande
Published: February 2021

In recent times, renewable energy demand is rapidly increasing worldwide. Offshore wind energy is one of the alternative solutions to the problems posed by non-renewable energy resources. The kinetic energy of the wind is converted to mechanical energy by using an offshore floating wind turbine (OFWT). The efficiency of the OFWT is dependent upon the vibrational effect induced by the environment. In this paper, for the mitigation of this vibrational effect, a new model of barge-type OFWT is designed by using an active control strategy called translational oscillator with a rotational actuator (TORA). The disturbance observer (DO) based advanced control techniques including robust backstepping sliding mode control (BSMC), backstepping integral sliding mode control (BISMC), backstepping nonsingular terminal sliding mode control (BNTSMC), and a new backstepping integral nonsingular terminal sliding mode control (BINTSMC) technique, are devised for the stabilization of OFWT model. The comparison of these techniques is carried out by using MATLAB/SIMULINK which validates the feasibility and correctness of the proposed OFWT model and control techniques.
Effect of sotagliflozin as an adjunct to insulin therapy on blood pressure and arterial stiffness in adults with type 1 diabetes: A post hoc pooled analysis of inTandem1 and inTandem2
Authors: Rodbard Helena W , Giaccari Andrea , Cariou Bertrand , Garg Satish , Davies Michael J , Seth Kiernan , Sawhney Sangeeta
Published: February 2021

Objective:

Evaluate the effect of sotagliflozin, a dual inhibitor of sodium glucose cotransporter (SGLT) 1 and 2, on arterial stiffness in patients with type 1 diabetes (T1D) treated with sotagliflozin as adjunct to optimized insulin therapy.

Methods:

In this post hoc analysis, indirect markers of arterial stiffness, including pulse pressure, mean arterial pressure (MAP), and double product, were calculated using observed systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse rate at 24 weeks using data from a pooled patient population from the inTandem1 and inTandem2 randomized controlled trials ( n = 1575).

Results:

Baseline characteristics were similar among groups. Relative to placebo at Week 24, sotagliflozin 200 mg and 400 mg reduced SBP by 2.03 mm Hg (95% CI −3.30 to −0.75; p = 0.0019) and 2.85 mm Hg (−4.12 to −1.57; p < 0.0001), respectively. DBP decreased by 1.1 and 0.9 mm Hg, MAP by 1.4 and 1.6 mm Hg, and double product by 202.5 and 221.1 bpm × mm Hg, respectively ( p < 0.05 for all). No increases in heart rate were observed.

Conclusion:

In adults with T1D, adding sotagliflozin to insulin significantly reduced blood pressure and other markers of arterial stiffness and vascular resistance.
Premenstrual dysphoric disorder
Authors: Khan Akhtar , Hardway Michael , Younas Kinza
Published: February 2021

An estimated 8-out-of-10 women experience physiological premenstrual symptoms, 3–30% of these women suffer with symptoms of premenstrual syndrome (PMS) that interfere with daily life, with 1–10% of women suffering from severe PMS symptoms meeting the DSM-5 criteria for diagnosis of premenstrual dysphoric disorder (PMDD). PMDD can be considered a subdivision of PMS and is a combination of psychological, behavioural and physical symptoms that can vary in intensity and presents cyclically during the luteal phase of ovulatory menstrual cycles. The diagnosis of PMDD and PMS depends on the timing of symptoms, the severity of symptoms and their impact on quality of life. Physiological symptoms (feeling bloated, headache, acne, mood changes and constipation) that do not impact on daily activities and quality of life are considered to be physiological premenstrual symptoms rather than PMS. There is no association with age, educational status or employment for PMS or PMDD.
Basal cell carcinoma
Authors: Alexander Paterson Luke
Published: February 2021

Basal cell carcinomas are the most common of all skin cancers, but are often overlooked, perhaps in the wake of increased public awareness of the dangers posed by malignant melanoma. The incidence has been increasing rapidly, adding to the workload of an already stretched primary and secondary care service. A better understanding of how these slow-growing lesions present and behave may help GPs to feel more comfortable managing patients in primary care.
Tree Species Diversity, Composition and Aboveground Biomass Across Dry Forest Land-Cover Types in Coastal Ecuador
Authors: Haro-Carrión Xavier , Loiselle Bette , Putz Francis E.
Published: February 2021

Tropical dry forests (TDF) are highly threatened ecosystems that are often fragmented due to land-cover change. Using plot inventories, we analyzed tree species diversity, community composition and aboveground biomass patterns across mature (MF) and secondary forests of about 25 years since cattle ranching ceased (SF), 10–20-year-old plantations (PL), and pastures in a TDF landscape in Ecuador. Tree diversity was highest in MF followed by SF, pastures and PL, but many endemic and endangered species occurred in both MF and SF, which demonstrates the importance of SF for species conservation. Stem density was higher in PL, followed by SF, MF and pastures. Community composition differed between MF and SF due to the presence of different specialist species. Some SF specialists also occurred in pastures, and all species found in pastures were also recorded in SF indicating a resemblance between these two land-cover types even after 25 years of succession. Aboveground biomass was highest in MF, but SF and Tectona grandis PL exhibited similar numbers followed by Schizolobium parahyba PL, Ochroma pyramidale PL and pastures. These findings indicate that although species-poor, some PL equal or surpass SF in aboveground biomass, which highlights the critical importance of incorporating biodiversity, among other ecosystem services, to carbon sequestration initiatives. This research contributes to understanding biodiversity conservation across a mosaic of land-cover types in a TDF landscape.
Application of bioluminescence resonance energy transfer-based cell tracking approach in bone tissue engineering
Authors: Wang Lufei , Lee Dong Joon , Han Han , Zhao Lixing , Tsukamoto Hiroshi , Kim Yong-IL , Musicant Adele M , Parag-Sharma Kshitij , Hu Xiangxiang , Tseng Henry C , Chi Jen-Tsan , Wang Zhengyan , Amelio Antonio L , Ko Ching-Chang
Published: February 2021

Bioluminescent imaging (BLI) has emerged as a popular in vivo tracking modality in bone regeneration studies stemming from its clear advantages: non-invasive, real-time, and inexpensive. We recently adopted bioluminescence resonance energy transfer (BRET) principle to improve BLI cell tracking and generated the brightest bioluminescent signal known to date, which thus enables more sensitive real-time cell tracking at deep tissue level. In the present study, we brought BRET-based cell tracking strategy into the field of bone tissue engineering for the first time. We labeled rat mesenchymal stem cells (rMSCs) with our in-house BRET-based GpNLuc reporter and evaluated the cell tracking efficacy both in vitro and in vivo. In scaffold-free spheroid 3D culture system, using BRET-based GpNLuc labeling resulted in significantly better correlation to cell numbers than a fluorescence based approach. In scaffold-based 3D culture system, GpNLuc-rMSCs displayed robust bioluminescence signals with minimal background noise. Furthermore, a tight correlation between BLI signal and cell number highlighted the robust reliability of using BRET-based BLI. In calvarial critical sized defect model, robust signal and the consistency in cell survival evaluation collectively supported BRET-based GpNLuc labeling as a reliable approach for non-invasively tracking MSC. In summary, BRET-based GpNLuc labeling is a robust, reliable, and inexpensive real-time cell tracking method, which offers a promising direction for the technological innovation of BLI and even non-invasive tracking systems, in the field of bone tissue engineering.
A unique cardiovascular presentation of pheochromocytoma
Authors: Orr William B , Chokshi Riti , Groh Georgeann , Silva Jennifer N Avari , Van Hare George F , Dalal Aarti S
Published: February 2021

We describe a unique presentation of a pheochromocytoma in a normotensive teenager, who presented with symptoms of headache, neck pain, and palpitations. Holter and event monitor tracings revealed intermittent junctional rhythm causing electromechanical dyssynchrony between atrial and ventricular contraction resulting in reported symptoms. Exercise stress testing helped correlate symptomatic junctional rhythm events to episodic hypertension which led to the eventual diagnosis of pheochromocytoma. The exercise test provided insight into the physiologic coupling that the sympathetic and parasympathetic autonomic nervous systems have on the cardiovascular system during exercise and exaggerated hypertension. The patient was found to have MEN2A and partial adrenalectomy resulted in complete resolution of symptoms and arrhythmia. This unusual presentation illustrates the benefit of a comprehensive clinical evaluation, which led to the eventual diagnosis.
Influence on proliferation and apoptosis of intestinal epithelial cells and expression of ACVR1 by Helicobacter pylori
Authors: Lin Yunfeng , Chen Min , Zhang Shuyu , Feng Zhichun , Wang Jingwen
Published: February 2021

To discuss the influence on proliferation and apoptosis of human intestinal epithelial cells by Helicobacter pylori (Hp). CCK-8 method and flow cytometry to test the influence on proliferation and apoptosis of intestinal epithelial cells by Hp and cell cycle distribution. Immunocytochemistry, qRT-PCR, and WB to analyze the expression and activation of ACVR1. Functional studies of TNBS-induced IBD on mice and DSS-induced IBD on C57BL/6J mice with HP used for intervention were also performed. Hp facilitated the proliferation of intestinal epithelial cells with the breeding ratios on the first and third day are 5.24% ± 3.26% and 34.18% ± 6.68% respectively. ACVR1 is activated and the expression of anti-apoptosis protein Bcl-2 and Bcl-XL is up-regulated. In vivo, TNBS-induced and Hp-induced exhibited inflammatory lesions of intestine, ACVR1 and Bcl-2 higher expressions as compared to wild-type mice. Hp is likely to play a very important role in the proliferation, apoptosis, and malignant transformation of intestinal epithelial cells through ACVR1 pathway.
BH3 profiling identifies ruxolitinib as a promising partner for venetoclax to treat T-cell prolymphocytic leukemia
Authors: Herbaux Charles , Kornauth Christoph , Poulain Stéphanie , Chong Stephen J. F. , Collins Mary C. , Valentin Rebecca , Hackett Liam , Tournilhac Olivier , Lemonnier François , Dupuis Jehan , Daniel Adrien , Tomowiak Cecile , Laribi Kamel , Renaud Loïc , Roos-Weil Damien , Rossi Cedric , Van Den Neste Eric , Leyronnas Cecile , Merabet Fatiha , Malfuson Jean Valère , Tiab Mourad , Ysebaert Loïc , Ng Samuel , Morschhauser Franck , Staber Philipp B. , Davids Matthew S.
Published: February 2021

Conventional therapies for patients with T-cell prolymphocytic leukemia (T-PLL), such as cytotoxic chemotherapy and alemtuzumab, have limited efficacy and considerable toxicity. Several novel agent classes have demonstrated preclinical activity in T-PLL, including inhibitors of the JAK/STAT and T-cell receptor pathways, as well as histone deacetylase (HDAC) inhibitors. Recently, the BCL-2 inhibitor venetoclax also showed some clinical activity in T-PLL. We sought to characterize functional apoptotic dependencies in T-PLL to identify a novel combination therapy in this disease. Twenty-four samples from patients with primary T-PLL were studied by using BH3 profiling, a functional assay to assess the propensity of a cell to undergo apoptosis (priming) and the relative dependence of a cell on different antiapoptotic proteins. Primary T-PLL cells had a relatively low level of priming for apoptosis and predominantly depended on BCL-2 and MCL-1 proteins for survival. Selective pharmacologic inhibition of BCL-2 or MCL-1 induced cell death in primary T-PLL cells. Targeting the JAK/STAT pathway with the JAK1/2 inhibitor ruxolitinib or HDAC with belinostat both independently increased dependence on BCL-2 but not MCL-1, thereby sensitizing T-PLL cells to venetoclax. Based on these results, we treated 2 patients with refractory T-PLL with a combination of venetoclax and ruxolitinib. We observed a deep response in JAK3-mutated T-PLL and a stabilization of the nonmutated disease. Our functional, precision-medicine–based approach identified inhibitors of HDAC and the JAK/STAT pathway as promising combination partners for venetoclax, warranting a clinical exploration of such combinations in T-PLL.
Clonal evolution of acute myeloid leukemia with FLT3-ITD mutation under treatment with midostaurin
Authors: Schmalbrock Laura K. , Dolnik Anna , Cocciardi Sibylle , Sträng Eric , Theis Frauke , Jahn Nikolaus , Panina Ekaterina , Blätte Tamara J. , Herzig Julia , Skambraks Sabrina , Rücker Frank G. , Gaidzik Verena I. , Paschka Peter , Fiedler Walter , Salih Helmut R. , Wulf Gerald , Schroeder Thomas , Lübbert Michael , Schlenk Richard F. , Thol Felicitas , Heuser Michael , Larson Richard A. , Ganser Arnold , Stunnenberg Hendrik G. , Minucci Saverio , Stone Richard M. , Bloomfield Clara D. , Döhner Hartmut , Döhner Konstanze , Bullinger Lars
Published: February 2021

In the international randomized phase 3 RATIFY (Randomized AML Trial In FLT3 in patients less than 60 Years old) trial, the multikinase inhibitor midostaurin significantly improved overall and event-free survival in patients 18 to 59 years of age with FLT3-mutated acute myeloid leukemia (AML). However, only 59% of patients in the midostaurin arm achieved protocol-specified complete remission (CR), and almost half of patients achieving CR relapsed. To explore underlying mechanisms of resistance, we studied patterns of clonal evolution in patients with FLT3-internal tandem duplications (ITD)-positive AML who were entered in the RATIFY or German-Austrian Acute Myeloid Leukemia Study Group 16-10 trial and received treatment with midostaurin. To this end, paired samples from 54 patients obtained at time of diagnosis and at time of either relapsed or refractory disease were analyzed using conventional Genescan-based testing for FLT3-ITD and whole exome sequencing. At the time of disease resistance or progression, almost half of the patients (46%) became FLT3-ITD negative but acquired mutations in signaling pathways (eg, MAPK), thereby providing a new proliferative advantage. In cases with FLT3-ITD persistence, the selection of resistant ITD clones was found in 11% as potential drivers of disease. In 32% of cases, no FLT3-ITD mutational change was observed, suggesting either resistance mechanisms bypassing FLT3 inhibition or loss of midostaurin inhibitory activity because of inadequate drug levels. In summary, our study provides novel insights into the clonal evolution and resistance mechanisms of FLT3-ITD–mutated AML under treatment with midostaurin in combination with intensive chemotherapy.
Time dependent effect of cold ischemia on the phosphoproteome and protein kinase activity in fresh-frozen colorectal cancer tissue obtained from patients
Authors: Buffart Tineke E. , van den Oord Rosanne A. H. M. , van den Berg Adriënne , Hilhorst Riet , Bastiaensen Niek , Pruijt Hans F. M. , van den Brule Adriaan , Nooijen Peet , Labots Mariette , de Goeij-de Haas Richard R. , Dekker Henk , Piersma Sander R. , Pham Thang V. , van der Leij Theo , de Wijn Rik , Ruijtenbeek Rob , Jiménez Connie R. , Verheul Henk M. W.
Published: February 2021

Background

Based on their potential to analyze aberrant cellular signaling in relation to biological function, kinase activity profiling in tumor biopsies by peptide microarrays and mass spectrometry-based phosphoproteomics may guide selection of protein kinase inhibitors in patients with cancer. Variable tissue handling procedures in clinical practice may influence protein phosphorylation status and kinase activity and therewith may hamper biomarker discovery. Here, the effect of cold ischemia time (CIT) on the stability of kinase activity and protein phosphorylation status in fresh-frozen clinical tissue samples was studied using peptide microarrays and mass spectrometry-based phosphoproteomics.

Methods

Biopsies of colorectal cancer resection specimens from five patients were collected and snap frozen immediately after surgery and at 6 additional time points between 0 and 180 min of CIT. Kinase activity profiling was performed for all samples using a peptide microarray. MS-based global phosphoproteomics was performed in tumors from 3 patients at 4 time points. Statistical and cluster analyses were performed to analyze changes in kinase activity and phosphoproteome resulting from CIT.

Results

Unsupervised cluster analysis of kinase activity and phosphoproteome data revealed that samples from the same patients cluster together. Continuous ANOVA analysis of all 7 time points for 5 patient samples resulted in 4 peptides out of 210 (2%) with significantly (p < 0.01 and fold change > 2) altered signal intensity in time. In 4 out of 5 patients tumor kinase activity was stable with CIT. MS-based phosphoproteomics resulted in the detection of 10,488 different phosphopeptides with on average 6044 phosphopeptides per tumor sample. 2715 phosphopeptides were detected in all samples at time point 0, of which 90 (3.3%) phosphopeptides showed significant changes in intensity with CIT (p < 0.01). Only two phosphopeptides were significantly changed in all time points, including one peptide (PKP3) with a fold change > 2.

Conclusions

The vast majority of the phosphoproteome as well as the activity of protein kinases in colorectal cancer resection tissue is stable up to 180 min of CIT and reflects tumor characteristics. However, specific changes in kinase activity with increasing CIT were observed. Therefore, stringent tissue collection procedures are advised to minimize changes in kinase activity during CIT.