bluuebunny/crossref_metadata_2025 huggingface dataset:
Donor genetic backgrounds contribute to the functional heterogeneity of stem cells and clinical outcomes
Authors: Wang Ting , Zhang Juan , Liao Jinqi , Zhang Fan , Zhou Guangqian
Published: August 2020

Stable and sustainable stem cell sources for stem cell-based therapies are scarce and a key bottleneck for clinical applications. The regenerative potential of stem cells is usually attributed to several allogeneic or even autologous donor-related factors. Genetic background and epigenetic variations in different individuals may significantly affect the functional heterogeneity of stem cells. Particularly, single-nucleotide polymorphisms (SNPs) have been implicated in diseases with monogenetic or multifactorial and complex genetic etiologies. However, the possible effects of individual SNPs on donor stem cells remain far from fully elucidated. In this Perspective, we will discuss the roles played by donor genetic traits in the functional heterogeneity of induced pluripotent stem cells, mesenchymal stem cells, and hematopoietic stem cells and their implications for regenerative medicine and therapy.

Significance statement In the past decades, thousands of genetic variations termed single-nucleotide polymorphisms (SNPs) have been identified, many of which are likely associated with complex human diseases that were previously hypothesized to have other unique genetic drivers. Genetic studies are rapidly being extended to stem cell research and regenerative medicine models. Considering the impact of SNPs in the etiology of diseases, it is reasonable to consider that stem cells carrying disease-associated SNPs should not be transplanted onto the recipients with the same disease.
Competition between branded and nonbranded firms and its impact on welfare
Authors: Pan Cong
Published: August 2020

We examine a quantity competition among branded and nonbranded firms. The market comprises two consumer segments: one purchases only branded products (the high‐end market), while the other segment's consumers purchase less expensive products (the low‐end market). When branded firms take actions sequentially, we show that the branded leader has an incentive to restrict its quantity to avoid entering the low‐end market. As the follower recognizes this incentive, it can restrict the leader by implementing a quantity constraint, which is affected by the number of nonbranded firms. We find that both the branded leader and follower could benefit from the nonbranded firms and that the leader prefers to have more nonbranded firms in the market than the follower does. Furthermore, we show that the free entry of nonbranded firms could negatively affect total surplus as well as consumer surplus even without any costs, because of the premium pricing of branded products.
Whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects
Authors: Malekizadeh Yasaman , Williams Gareth , Kelson Mark , Whitfield David , Mill Jonathan , Collier David A. , Ballard Clive , Jeffries Aaron R. , Creese Byron
Published: August 2020

Background

Stroke/thromboembolic events, infections, and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events.

Methods

Whole transcriptome signatures were generated for SH‐SY5Y cells treated with amisulpride, risperidone, and volinanserin using RNA sequencing. Bioinformatic analysis was performed that scored the association between antipsychotic signatures and expression data from 415,252 samples in the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) repository.

Results

Atherosclerosis, venous thromboembolism, and influenza NCBI GEO‐derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (eg, brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor [PDGFR]‐beta, tumor necrosis factor [TNF], transforming growth factor [TGF]‐beta, selenoamino acid metabolism, and influenza infection).

Conclusions

These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
Followership Education for Postsecondary Students
Authors: Jenkins Daniel M. , Spranger Angela N.
Published: August 2020

Many universities offer one or more courses on leadership that include followership as a topic. A few have offered a complete course on followership. However, there is little information on postsecondary followership training. This chapter explores the unique issues of introducing followership to students, many of whom have been told their entire lives that leadership is everything. This chapter highlights followership courses and programs at institutions that offer them, and explores the delivery of current practices, with suggestions for increasing efficacy.
Using Storytelling to Teach Effective Followership
Authors: Underkofler Michael , Rossi Stephanie , Korbal Edward
Published: August 2020

This chapter examines the craft of storytelling for the purpose of developing followers and exploring leader‐follower transitions, while offering storytelling methods, classroom activities, and critical components of crafting a story. Through stories about the American Civil Rights icon, Mrs. Rosa Parks, and an unfamiliar Civil Rights activist, Sister Madeline Dorsey, a humble leader turned effective follower, it is possible to more easily appreciate the reflexive transition of follower to leader and leader to follower.
Leader–Follower Synergies: Lessons From Nelson and His Captains
Authors: Pascoe Bruce
Published: August 2020

Lord Nelson was a master of leading fleets into battle. He was also a master of leading people, instinctively understanding the value of both leadership and followership. This chapter explores the leadership behaviors Nelson used to create a powerful leader/follower synergy between him and his captains, and introduces a model based on these behaviors. While the situations presented in this chapter are military, the focus is on behavioral lessons that can be taught to students and applied in a broad range of organizational settings.
Offene und endovaskuläre Versorgung des infrarenalen vs. juxtarenalen Bauchaortenaneurysmas
Authors: Schmitz-Rixen T. , Steffen M. , Böckler D. , Grundmann R. T.
Published: August 2020

Hintergrund und Zielsetzung

Die vorliegende Untersuchung geht der Frage nach, wie sich die perioperativen Ergebnisse bei elektiver Versorgung juxtarenaler abdomineller Aortenaneurysmen (AAA) von denen bei Versorgung infrarenaler AAA unterscheiden.

Material und Methoden

Datenbasis ist das AAA-Register des Deutschen Instituts für Gefäßmedizinische Gesundheitsforschung (DIGG) der Deutschen Gesellschaft für Gefäßchirurgie und Gefäßmedizin (DGG) der Jahre 2013–2017 mit insgesamt 18.629 Patienten, 17.026 (91,4 %) mit infrarenalem und 1603 (8,6 %) mit juxtarenalem AAA. Bei den infrarenalen AAA wurden 80,5 % (n = 13.707) endovaskulär (EVAR) und 3319 (19,5 %) offen (OAR) versorgt, bei den juxtarenalen waren es 786 Patienten mit EVAR (49,0 %) und 817 (51,0 %) mit OAR.

Ergebnisse

Sowohl bei OAR als auch bei EVAR waren Patienten mit juxtarenalen AAA in ihren Ausgangsbedingungen nicht mit Patienten mit infrarenalen AAA vergleichbar. Der Frauenanteil war bei juxtarenalen AAA signifikant höher (bei EVAR 16,9 % vs. 13,1 %, bei OAR 18,6 % vs. 16,0 %) und der Aneurysmadurchmesser war signifikant größer (bei EVAR 57,8 vs. 54,3 mm, bei OAR 59,0 vs. 56,3 mm). Patienten mit juxtarenalem AAA zeigten signifikant häufiger als Patienten mit infrarenalem AAA bereits präoperativ eine eingeschränkte Nierenfunktion (12,5 % vs. 9,7 % bei EVAR, 14,4 % vs. 9,4 % bei OAR). Die Klinikletalität betrug bei EVAR 1,0 % (infrarenale AAA) vs. 5,7 % (juxtarenale AAA) (p = 0,000), bei OAR 4,2 % (infrarenale AAA) vs. 7,7 % (juxtarenale AAA) (p = 0,000). Zu einer postoperativen Verschlechterung der Nierenfunktion kam es bei EVAR in 2,0 % der Fälle mit infrarenalen AAA vs. 12,2 % bei juxtarenalen AAA (p = 0,000), bei OAR in 7,9 % vs. 19,5 % (p = 0,000).

Schlussfolgerungen

Im vorliegenden Krankengut waren die Raten an postoperativen Komplikationen sowie die postoperative Sterblichkeit bei Versorgung juxtarenaler AAA signifikant höher als bei Versorgung infrarenaler AAA, das galt sowohl für EVAR als auch für OAR. Inwieweit dies an den ungünstigeren Ausgangsbedingungen bei Patienten mit juxtarenalen AAA lag und welche Rolle die gewählte Operationstechnik dabei spielte, sollte in weiteren Erhebungen überprüft werden.
Nudging in education: from theory towards guidelines for successful implementation
Authors: Weijers Robert J. , de Koning Björn B. , Paas Fred
Published: August 2020

Nudging is one of the strategies from behavioral economics that aims to influence behavior by changing the environment. We propose that it could also be a valuable means to influence behavior in educational contexts. However, implementation of nudging in education is yet sparse. We describe the relevant issues to consider when applying nudging in education, arguing that a focus on the long-term effects and underlying processes of a nudge is necessary for successful implementation. Then, we aim to facilitate this implementation of nudging in education by making a distinction between nudges that is relevant for overcoming these issues. Based on the framework proposed by Hansen and Jespersen (European Journal of Risk Regulation, 4(1), 3–28, 2013), we distinguish between Type 1 and Type 2 nudges, and transparent and non-transparent nudges, resulting in four nudge categories. For each of these nudge categories, we determine its suitability for different educational goals. The resulting decision matrix can help researchers and practitioners when designing nudges for an educational context.
A Rapid Qualitative Assessment of the Impact of the COVID-19 Pandemic on a Racially/Ethnically Diverse Sample of Gay, Bisexual, and Other Men who Have Sex with Men Living with HIV in the US South
Authors: Rhodes Scott D. , Mann-Jackson Lilli , Alonzo Jorge , Garcia Manuel , Tanner Amanda E. , Smart Benjamin D. , Horridge Danielle N. , Van Dam Cornelius N. , Wilkin Aimee M.
Published: August 2020

Persons living with HIV (PLWH) may be at increased risk for severe COVID-19-related illness. Our community-based participatory research partnership collected and analyzed semi-structured interview data to understand the early impact of the COVID-19 pandemic on a sample of racially/ethnically diverse gay, bisexual, and other men who have sex with men living with HIV. Fifteen cisgender men participated; their mean age was 28. Six participants were Black/African American, five were Spanish-speaking Latinx, and four were White. Seventeen themes emerged that were categorized into six domains: knowledge and perceptions of COVID-19; COVID-19 information sources and perceptions of trustworthiness; impact of COVID-19 on behaviors, health, and social determinants of health; and general COVID-19-related concerns. Interventions are needed to ensure that PLWH have updated information and adhere to medication regimens, and to reduce the impact of COVID-19 on social isolation, economic stability, healthcare access, and other social determinants of health within this vulnerable population.
Three Planctomycetes isolated from biotic surfaces in the Mediterranean Sea and the Pacific Ocean constitute the novel species Symmachiella dynata gen. nov., sp. nov. and Symmachiella macrocystis sp. nov.
Authors: Salbreiter Markus , Waqqas Muhammad , Jogler Mareike , Kallscheuer Nicolai , Wiegand Sandra , Peeters Stijn H. , Heuer Anja , Jetten Mike S. M. , Boedeker Christian , Rast Patrick , Rohde Manfred , Jogler Christian
Published: August 2020

Planctomycetes is a phylum of environmentally important bacteria, which also receive significant attention due to their fascinating cell biology. Access to axenic Planctomycete cultures is crucial to study cell biological features within this phylum in further detail. In this study, we characterise three novel strains, Mal52T, Pan258 and CA54T, which were isolated close to the coasts of the islands Mallorca (Spain) and Panarea (Italy), and from Monterey Bay, CA, USA. The three isolates show optimal growth at temperatures between 22 and 24 °C and at pH 7.5, divide by polar budding, lack pigmentation and form strong aggregates in liquid culture. Analysis of five phylogenetic markers suggests that the strains constitute two novel species within a novel genus in the family Planctomycetaceae. The strains Mal52T (DSM 101177T = VKM B-3432T) and Pan258 were assigned to the species Symmachiella dynata gen nov., sp. nov., while strain CA54T (DSM 104301T = VKM B-3450T) forms a separate species of the same genus, for which we propose the name Symmachiella macrocystis sp. nov.
Addressing the Grid-Size Sensitivity Issue in Large-Eddy Simulations of Stable Boundary Layers
Authors: Dai Yi , Basu Sukanta , Maronga Björn , de Roode Stephan R.
Published: August 2020

We have identified certain fundamental limitations of a mixing-length parametrization used in a popular turbulent kinetic energy-based subgrid-scale model. Replacing this parametrization with a more physically realistic one significantly improves the overall quality of the large-eddy simulation (LES) of stable boundary layers. For the range of grid sizes considered here (specifically, 1 m–12.5 m), the revision dramatically reduces the grid-size sensitivity of the simulations. Most importantly, the revised scheme allows us to reliably estimate the first- and second-order statistics of a well-known LES intercomparison case, even with a coarse grid size of O(10 m).
Bioenergy technologies in long-run climate change mitigation: results from the EMF-33 study
Authors: Daioglou Vassilis , Rose Steven K. , Bauer Nico , Kitous Alban , Muratori Matteo , Sano Fuminori , Fujimori Shinichiro , Gidden Matthew J. , Kato Etsushi , Keramidas Kimon , Klein David , Leblanc Florian , Tsutsui Junichi , Wise Marshal , van Vuuren Detlef P.
Published: August 2020

Bioenergy is expected to play an important role in long-run climate change mitigation strategies as highlighted by many integrated assessment model (IAM) scenarios. These scenarios, however, also show a very wide range of results, with uncertainty about bioenergy conversion technology deployment and biomass feedstock supply. To date, the underlying differences in model assumptions and parameters for the range of results have not been conveyed. Here we explore the models and results of the 33rd study of the Stanford Energy Modeling Forum to elucidate and explore bioenergy technology specifications and constraints that underlie projected bioenergy outcomes. We first develop and report consistent bioenergy technology characterizations and modeling details. We evaluate the bioenergy technology specifications through a series of analyses—comparison with the literature, model intercomparison, and an assessment of bioenergy technology projected deployments. We find that bioenergy technology coverage and characterization varies substantially across models, spanning different conversion routes, carbon capture and storage opportunities, and technology deployment constraints. Still, the range of technology specification assumptions is largely in line with bottom-up engineering estimates. We then find that variation in bioenergy deployment across models cannot be understood from technology costs alone. Important additional determinants include biomass feedstock costs, the availability and costs of alternative mitigation options in and across end-uses, the availability of carbon dioxide removal possibilities, the speed with which large scale changes in the makeup of energy conversion facilities and integration can take place, and the relative demand for different energy services.
Ethics of digital contact tracing and COVID-19: who is (not) free to go?
Authors: Klenk Michael , Duijf Hein
Published: August 2020

Digital tracing technologies are heralded as an effective way of containing SARS-CoV-2 faster than it is spreading, thereby allowing the possibility of easing draconic measures of population-wide quarantine. But existing technological proposals risk addressing the wrong problem. The proper objective is notsolelyto maximise the ratio of people freed from quarantine but to also ensure that the composition of the freed group is fair. We identify several factors that pose a risk for fair group composition along with an analysis of general lessons for a philosophy of technology. Policymakers, epidemiologists, and developers can use these risk factors to benchmark proposal technologies, curb the pandemic, and keep public trust.
Ordinal patterns in clusters of subsequent extremes of regularly varying time series
Authors: Oesting Marco , Schnurr Alexander
Published: August 2020

In this paper, we investigate temporal clusters of extremes defined as subsequent exceedances of high thresholds in a stationary time series. Two meaningful features of these clusters are the probability distribution of the cluster size and the ordinal patterns giving the relative positions of the data points within a cluster. Since these patterns take only the ordinal structure of consecutive data points into account, the method is robust under monotone transformations and measurement errors. We verify the existence of the corresponding limit distributions in the framework of regularly varying time series, develop non-parametric estimators and show their asymptotic normality under appropriate mixing conditions. The performance of the estimators is demonstrated in a simulated example and a real data application to discharge data of the river Rhine.
Being highly prolific in academic science: characteristics of individuals and their departments
Authors: Fox Mary Frank , Nikivincze Irina
Published: August 2020

The prolific (exceptionally high producers of scholarly publications) are strategic to the study of academic science. The highly prolific have been drivers of research activity and impact and are a window into the stratification that exists. For these reasons, we address key characteristics associated with being highly prolific. Doing this, we take a social-organizational approach and use distinctive survey data on both social characteristics of scientists and features of their departments, reported by US faculty in computer science, engineering, and sciences within eight US research universities. The findings point to a telling constellation of hierarchical advantages: rank, collaborative span, and favorable work climate. Notably, once we take rank into account, gender is not associated with being prolific. These findings have implications for understandings of being prolific, systems of stratification, and practices and policies in higher education.
‘I Felt Like I was Floating in Space’: Autistic Adults’ Experiences of Low Mood and Depression
Authors: Jordan Amy Louise , Marczak Magdalena , Knibbs Jacqueline
Published: August 2020

It is recognised that a high proportion of adults on the autism spectrum experience depressive symptoms. However, limited research has explored autistic peoples’ experiences of low mood and depression. The aim of this study was to explore the lived experiences of low mood and depression for adults on the autism spectrum. The study employed Interpretive Phenomenological Analysis to investigate the experiences of 8 adults (7 males and 1 female), aged between 19 and 51, who had a diagnosis of autism without co-occurring learning disabilities, and experienced low mood or depression. All participants recorded their thoughts and feelings in a mood diary for 1 week and participated in a semi-structured interview. Three superordinate themes emerged from the data: ‘Autism has made me the person I am’, ‘I can’t function in the world’ and ‘It’s like trying to do accounts on the futures market’: Making sense of emotions. Findings highlight a need for specialist mental health provision for adults who are on the autism spectrum. Limitations of this study and implications for future research are discussed.
Online scheduling of car-sharing request pairs between two locations
Authors: Luo Kelin , Xu Yinfeng , Liu Haodong
Published: August 2020

We consider an online car-sharing problem between two locations with advance bookings. Each customer submits a pair of requests, where each request specifies the pick-up time and the pick-up location: one request from A to B, and the other request from B to A, not necessary in this order. The scheduler aims to maximize the number of satisfied customers, where the schedule has to decide whether or not to accept a request pair immediately at the time when the request pair is submitted. This problem is called OnlineTransfersForCommuting. We present lower bounds on the competitive ratio for this problem with both fixed booking times and variable booking times, and propose two algorithms, greedy algorithm and balanced greedy algorithm, that achieve the best possible competitive ratios.
Prevalence of Intimate Partner Violence and Association with Wealth in Myanmar
Authors: Larsen Lise Wessel , Aye Win Thuzar , Bjertness Espen
Published: August 2020

This study explores the prevalence of physical, sexual and emotional intimate partner violence in Myanmar, attitudes towards violence, and the association between wealth and intimate partner violence. We analysed a nationally representative sample of 3425 married women aged 15–49 years from Myanmar Demographic and Health survey 2015–2016. In this cross-sectional study, data was collected by in-person interviews using a standardized questionnaire. Wealth was operationalized into five groups depending on how much the household owns. Intimate partner violence was measured based on the standard methods of Demographic and Health Survey. The overall prevalence of intimate partner violence (physical, sexual and emotional) was 20.6% (95% confidence interval (95% CI) 18.9–22.3). Less severe physical intimate partner violence was reported by 14.8% (95% CI 13.5–16.3), while 4.4% (95% CI 3.8–5.2) reported severe physical violence. The prevalence of sexual and emotional violence were 2.8% (95% CI 2.2–3.6) and 13.1% (95% CI 11.7–14.6), respectively. Many women believed that a husband has the right to beat his wife if she acts inappropriate, with the highest prevalence at 43% of the women justifying beating if the wife neglects her children. In logistic regression analysis, low wealth as compared with higher wealth, was associated with a higher prevalence of intimate partner violence. The results reveals that intimate partner violence against ever-married women in Myanmar is present, that many women justify beating, and that wealth and intimate partner violence is associated.
Global Stabilization of Two Dimensional Viscous Burgers’ Equation by Nonlinear Neumann Boundary Feedback Control and Its Finite Element Analysis
Authors: Kundu Sudeep , Pani Amiya Kumar
Published: August 2020

In this article, global stabilization results for the two dimensional viscous Burgers’ equation, that is, convergence of unsteady solution to its constant steady state solution with any initial data, are established using a nonlinear Neumann boundary feedback control law. Then, applying $$C^0$$

C
0

-conforming finite element method in spatial direction, optimal error estimates in $$L^\infty (L^2)$$

L
∞

(

L
2

)

and in $$L^\infty (H^1)$$

L
∞

(

H
1

)

-norms for the state variable and convergence result for the boundary feedback control law are derived. All the results preserve exponential stabilization property. Finally, several numerical experiments are conducted to confirm our theoretical findings.
Spatially-Adaptive Variational Reconstructions for Linear Inverse Electrical Impedance Tomography
Authors: Huska M. , Lazzaro D. , Morigi S. , Samorè A. , Scrivanti G.
Published: August 2020

The inverse electrical impedance tomography (EIT) problem involves collecting electrical measurements on the smooth boundary of a region to determine the spatially varying electrical conductivity distribution within the bounded region. Effective applications of EIT technology emerged in different areas of engineering, technology, and applied sciences. However, the mathematical formulation of EIT is well known to suffer from a high degree of nonlinearity and severe ill-posedness. Therefore, regularization is required to produce reasonable electrical impedance images. Using difference imaging, we propose a spatially-variant variational method which couples sparsity regularization and smoothness regularization for improved EIT linear reconstructions. The EIT variational model can benefit from structural prior information in the form of an edge detection map coming either from an auxiliary image of the same object being reconstructed or automatically detected. We propose an efficient algorithm for minimizing the (non-convex) function based on the alternating direction method of multipliers. Experiments are presented which strongly indicate that using non-convex versus convex variational EIT models holds the potential for more accurate reconstructions.
Blockchain Signaling System (BloSS): Cooperative Signaling of Distributed Denial-of-Service Attacks
Authors: Rodrigues Bruno , Scheid Eder , Killer Christian , Franco Muriel , Stiller Burkhard
Published: August 2020

Distributed Denial-of-Service (DDoS) attacks are one of the major causes of concerns for communication service providers. When an attack is highly sophisticated and no countermeasures are available directly, sharing hardware and defense capabilities become a compelling alternative. Future network and service management can base its operations on equally distributed systems to neutralize highly distributed DDoS attacks. A cooperative defense allows for the combination of detection and mitigation capabilities, the reduction of overhead at a single point, and the blockage of malicious traffic near its source. Main challenges impairing the widespread deployment of existing cooperative defense are: (a) high complexity of operation and coordination, (b) need for trusted and secure communications, (c) lack of incentives for service providers to cooperate, and (d) determination on how operations of these systems are affected by different legislation, regions, and countries. The cooperative Blockchain Signaling System (BloSS) defines an effective and alternative solution for security management, especially cooperative defenses, by exploiting Blockchains (BC) and Software-Defined Networks (SDN) for sharing attack information, an exchange of incentives, and tracking of reputation in a fully distributed and automated fashion. Therefore,BloSSwas prototyped and evaluated through a global experiment, without the burden to maintain, design, and develop special registries and gossip protocols.
Isoflurane promotes proliferation of squamous cervical cancer cells through mTOR-histone deacetylase 6 pathway
Authors: Zhang Wenwen , Xue Fang , Xie Shangdan , Chen Cheng , Li Jingwei , Zhu Xueqiong
Published: August 2020

This study investigated the effect of isoflurane on the proliferation of squamous cervical cancer cells, with focus on histone deacetylase 6 that is closely related to carcinogenesis. Squamous cervical cancer cells SiHa and Caski were exposed to 1%, 2%, or 3% isoflurane for 2 h, respectively. Cell proliferation was measured with the cell counting kit (CCK-8) assay and determined by BrdU assay. Expression of histone deacetylase 6, phospho-AKT, phospho-mTOR, and proliferating cell nuclear antigen (PCNA) was assessed by Western blot. In order to block the histone deacetylase 6 (HDAC6) expression, siRNA transfection was performed. Isoflurane significantly promoted the proliferation of both SiHa and Caski cells, accompanied by upregulation of PCNA protein expression. Isoflurane increased the level of histone deacetylase 6 protein expression in both cells, and knockdown of histone deacetylase 6 attenuated the pro-proliferation effects of isoflurane. Additionally, activation of AKT/mTOR was found after isoflurane treatment, and mTOR inhibition abolished isoflurane-induced histone deacetylase 6 expression. However, inhibition of AKT phosphorylation had no effect on the expression of histone deacetylase 6 mediated by isoflurane. In conclusion, Isoflurane enhanced proliferation of cervical cancer cells through upregulation of histone deacetylase 6, which was associated with mTOR-dependent pathway, but not AKT-mediated pathway.
Do Doctors Differentiate Between Suicide and Physician-Assisted Death? A Qualitative Study into the Views of Psychiatrists and General Practitioners
Authors: Pronk Rosalie , Willems Dick L. , van de Vathorst Suzanne
Published: August 2020

Physician-assisted death for patients suffering from psychiatric disorders is allowed in the Netherlands under certain circumstances. One of the central problems that arise with regard to this practice is the question of whether it is possible to distinguish between suicidality and a request for physician-assisted death. We set up this study to gain insight into how psychiatrists and general practitioners distinguish between suicidality and physician-assisted death. The data for this study were collected through qualitative interviews with 20 general practitioners and 17 psychiatrists in the Netherlands. From the interviews, we conclude that physicians distinguish three types of death wishes among patients suffering from psychiatric disorders: ‘impulsive suicidality,’ ‘chronic suicidality,’ and ‘rational death wishes.’ To discern between them they evaluate whether the death wish is seen as part of the psychopathology, whether it is consistent over time, and whether they consider it treatable. Some considered physician-assisted death an alternative to a ‘rational suicide,’ as this was perceived to be a more humane manner of death for the patient and their relatives. We argue that physician-assisted death can be justified also in some cases in which the death wish is part of the psychopathology, as the patient’s suffering can be unbearable and irremediable. Physician-assisted death in these cases may remain the only option left to relieve the suffering.
On the universality of the quantum approximate optimization algorithm
Authors: Morales M. E. S. , Biamonte J. D. , Zimborás Z.
Published: August 2020

The quantum approximate optimization algorithm (QAOA) is considered to be one of the most promising approaches towards using near-term quantum computers for practical application. In its original form, the algorithm applies two different Hamiltonians, called the mixer and the cost Hamiltonian, in alternation with the goal being to approach the ground state of the cost Hamiltonian. Recently, it has been suggested that one might use such a set-up as a parametric quantum circuit with possibly some other goal than reaching ground states. From this perspective, a recent work (Lloyd, arXiv:1812.11075) argued that for one-dimensional local cost Hamiltonians, composed of nearest neighbour ZZ terms, this set-up is quantum computationally universal and provides a universal gate set, i.e. all unitaries can be reached up to arbitrary precision. In the present paper, we complement this work by giving a complete proof and the precise conditions under which such a one-dimensional QAOA might produce a universal gate set. We further generalize this type of gate-set universality for certain cost Hamiltonians with ZZ and ZZZ terms arranged according to the adjacency structure of certain graphs and hypergraphs.
Living with hypoparathyroidism: development of the Hypoparathyroidism Patient Experience Scale-Impact (HPES-Impact)
Authors: Brod Meryl , Waldman Laura Tesler , Smith Alden , Karpf David
Published: August 2020

Purpose

Hypoparathyroidism (HP) is a rare endocrine disorder characterized by absent or inappropriately low levels of circulating parathyroid hormone (PTH). Research indicates that HP patients on conventional therapy may have a reduced quality of life. The study’s purpose was to develop a new disease-specific measure of the impacts of hypoparathyroidism on functioning and well-being and provide evidence for its content validity based on rigorous qualitative research methodologies for patient-reported outcomes development.

Methods

Semi-structured, individual concept elicitation (CE) interviews were conducted with 5 clinical experts and 42 adults in the USA with HP to identify impacts of relevance and importance to the target population. Transcripts were coded and analyzed using an adapted grounded theory approach common to qualitative research. Following item generation, the draft measure was cognitive debriefed in an independent sample of 16 adults with HP.

Results

Analyses identified four impact domains: physical functioning, including ability to exercise (n = 32, 76%) and mobility (n = 21, 50%); daily life, including ability to do things around the home (n = 33, 79%), and interference with work productivity (n = 18, 43%); psychological well-being, including feeling anxious/anxiety (n = 34, 81%) and frustrated (n = 27, 64%); and social, including ability to participate in social activities (n = 33, 79%) and relationships (n = 32, 76%). Twenty-seven impacts were identified and included in the preliminary measure. After the cognitive debriefing, a validation-ready, 26-item Hypoparathyroidism Patient Experience Scale-Impact (HPES-Impact) was generated.

Conclusion

Findings provide substantial evidence of content validity for the validation-ready HPES-Impact in adults with HP.
Effect of Renin-Angiotensin-Aldosterone System Inhibitors in Patients with COVID-19: a Systematic Review and Meta-analysis of 28,872 Patients
Authors: Baral Ranu , White Madeline , Vassiliou Vassilios S
Published: August 2020

Purpose of Review

The role of renin-angiotensin-aldosterone system (RAAS) inhibitors, notably angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs), in the COVID-19 pandemic has not been fully evaluated. With an increasing number of COVID-19 cases worldwide, it is imperative to better understand the impact of RAAS inhibitors in hypertensive COVID patients. PubMed, Embase and the pre-print database Medrxiv were searched, and studies with data on patients on ACEi/ARB with COVID-19 were included. Random effects models were used to estimate the pooled mean difference with 95% confidence interval using Open Meta[Analyst] software.

Recent Findings

A total of 28,872 patients were included in this meta-analysis. The use of any RAAS inhibition for any conditions showed a trend to lower risk of death/critical events (OR 0.671, CI 0.435 to 1.034, p = 0.071). Within the hypertensive cohort, however, there was a significant lower association with deaths (OR 0.664, CI 0.458 to 0.964, p = 0.031) or the combination of death/critical outcomes (OR 0.670, CI 0.495 to 0.908, p = 0.010). There was no significant association of critical/death outcomes within ACEi vs non-ACEi (OR 1.008, CI 0.822 to 1.235, p = 0.941) and ARB vs non-ARB (OR 0.946, CI 0.735 to 1.218, p = 0.668).

This is the largest meta-analysis including critical events and mortality data on patients prescribed ACEi/ARB and found evidence of beneficial effects of chronic ACEi/ARB use especially in hypertensive cohort with COVID-19. As such, we would strongly encourage patients to continue with RAAS inhibitor pharmacotherapy during the COVID-19 pandemic.
Loneliness among Elderly People: Can Food and Meals Change this Situation?
Authors: Hansen Kai Victor
Published: August 2020

In a relationship, it is natural that one person lives longer than the other, leading to many challenges, including the possibility of loneliness. This article focuses on how food and meals can help reduce loneliness among the elderly. There are many reasons for loneliness or emptiness, including being a widow or a widower, illness, and poverty. As the number of elderly people is greatly increasing in all welfare states, meals are an important function that should be maintained throughout life. This study used CurroCus® group interviews, or fast focus groups. Nine CurroCus® groups were conducted, lasting for 37–56 min (average = 45 min). Altogether, 76 persons participated, ranging in age from 60 to 87 years; participants were predominantly female (> 80%). The collected empirical data were recorded, transcribed, and entered into NVivo 11.0. Interviews were analysed using a grounded theory approach. The main findings of this article fall into two main categories: togetherness and life action. Based on the interpretation of respondents’ answers, elderly people make both conscious and unconscious choices that help reduce loneliness. They also gather around food and meals to experience more togetherness. In future research, loneliness strategies carried out unknowingly should be investigated more closely. In addition, elderly participants should self-report on meal activities throughout the day.
The Impact of MTHFR 1298 A > C and 677 C > T Gene Polymorphisms as Susceptibility Risk Factors in Cervical Intraepithelial Neoplasia Related to HPV and Sexually Transmitted Infections
Authors: Sohrabi Amir , Bassam-Tolami Fatemeh , Imani Mohsen
Published: August 2020

Background

HPV genotypes are the most common etiological factor for genital neoplasia. It would appear that sexually transmitted infections accompanied with HPV genotypes might have synergistic interactions in cancer progression. The genetic polymorphisms are involved in metabolizing carcinogens which may contribute to the susceptibility of developing genital cancers by less efficient or overly down metabolic pathways and cell signaling. MTHFR polymorphisms are related to several metabolic disorders and human cancers. We investigated the contribution of MTHFR 1298 and MTHFR 677 polymorphisms as potential risk factors for outcomes with HPV genotypes and STIs in Iranian population.

Materials and Methods

As a case–control study, MTHFR A1298C and C677T were assessed for SNPs analysis using a PCR–RFLP assay in 50 cervical intraepithelial neoplasia (CIN) cases, 98 HPV-positive subjects and 47 non-cancerous/non-HPV patients as healthy controls.

Results

Finding suggested a significant association between the MTHFR 1298 CC polymorphisms (OR = 3.5, 95% CI = 1.13–10.82, P ≤ 0.05) in women with CIN as compared to non-cancerous/non-HPV subjects. There was not a significant difference of MTHFR 677 between outcomes.

Discussion

It would seem MTHFR 1298 CC is more likely to be a potential risk factor for HPV–cervical cancer progression. Consequences support further attempts to understand the clinical manifestations of neoplasia related to genital infections and gene mutations.
The Direct Effect of Taxes and Transfers on Changes in the U.S. Income Distribution, 1967–2015
Authors: Wimer Christopher , Parolin Zachary , Fenton Anny , Fox Liana , Jencks Christopher
Published: August 2020

Scholars have increasingly drawn attention to rising levels of income inequality in the United States. However, prior studies have provided an incomplete account of how changes to specific transfer programs have contributed to changes in income growth across the distribution. Our study decomposes the direct effects of tax and transfer programs on changes in the household income distribution from 1967 to 2015. We show that despite a rising Gini coefficient, lower-tail inequality (the ratio of the 50th to 10th percentile) declined in the United States during this period due to the rise of in-kind and tax-based transfers. Food assistance and refundable tax credits account for nearly all the income growth between 1967 and 2015 at the 5th percentile and roughly one-half the growth at the 10th percentile. Moreover, income gains near the bottom of the distribution are concentrated among households with children. Changes in the income distribution were far less progressive among households without children.
The Wealth of Parents: Trends Over Time in Assortative Mating Based on Parental Wealth
Authors: Wagner Sander , Boertien Diederik , Gørtz Mette
Published: August 2020

This article describes trends in parental wealth homogamy among union cohorts formed between 1987 and 2013 in Denmark. Using high-quality register data on the wealth of parents during the year of partnering, we show that the correlation between partners’ levels of parental wealth is considerably lower compared with estimates from research on other countries. Nonetheless, parental wealth homogamy is high at the very top of the parental wealth distribution, and individuals from wealthy families are relatively unlikely to partner with individuals from families with low wealth. Parental wealth correlations among partners are higher when only parental assets rather than net wealth are examined, implying that the former might be a better measure for studying many social stratification processes. Most specifications indicate that homogamy increased in the 2000s relative to the 1990s, but trends can vary depending on methodological choices. The increasing levels of parental wealth homogamy raise concerns that over time, partnering behavior has become more consequential for wealth inequality between couples.
Transition to multiple mini interview (MMI) interviewing for medical school admissions
Authors: Langer Tessa , Ruiz Colby , Tsai Perry , Adams Ursula , Powierza Camilla , Vijay Ammu , Alvarez Paul , Dallahan Gary Beck , Rahangdale Lisa
Published: August 2020

Introduction The multiple mini interview (MMI) has been incorporated into the holistic review process in the selection of students to US medical schools. The MMI has been used to evaluate interpersonal and intrapersonal attributes which are deemed as necessary for future physicians. We hypothesized that there would be little difference in overall MMI evaluation data compared with traditional interview ratings.

Methods The University of North Carolina School of Medicine developed an interview process that included a traditional interview and MMI format during the 2019 admissions cycle. Evaluation data along with key demographic variables for 608 MD program applicants were analyzed using descriptive and inferential statistical analyses.

Results The MMI format slightly favored female over male applicants (p = 0.002) but did not select for or against applicants based on age, race/ethnicity, underserved/rural area upbringing, or indicators of disadvantage. Out of 608 applicants, 356 (59%) completed a post-interview survey in which the experience was positively rated.

Discussion Based on our experience, the use of a hybrid model of traditional interviews complemented with MMI stations provided greater details in the assessment of medical school applicants while obtaining equivalent data and acceptability amongst applicants.
Hydroxychloroquine in COVID-19: Potential Mechanism of Action Against SARS-CoV-2
Authors: Satarker Sairaj , Ahuja Tejas , Banerjee Madhuparna , E Vignesh Balaji , Dogra Shagun , Agarwal Tushar , Nampoothiri Madhavan
Published: August 2020

Purpose of Review

The rapid spread of virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has turned out to be a global emergency. Symptoms of this viral infection, coronavirus disease 2019 (COVID-19), include mild infections of the upper respiratory tract, viral pneumonia, respiratory failure, multiple organ failure and death. Till date, no drugs have been discovered to treat COVID-19 patients, and therefore, a considerable amount of interest has been shown in repurposing the existing drugs.

Recent Findings

Out of these drugs, chloroquine (CQ) and hydroxychloroquine (HCQ) have demonstrated positive results indicating a potential antiviral role against SARS-CoV-2. Its mechanism of action (MOA) includes the interference in the endocytic pathway, blockade of sialic acid receptors, restriction of pH mediated spike (S) protein cleavage at the angiotensin-converting enzyme 2 (ACE2) binding site and prevention of cytokine storm. Unfortunately, its adverse effects like gastrointestinal complications, retinopathy and QT interval prolongation are evident in treated COVID-19 patients. Yet, multiple clinical trials have been employed in several countries to evaluate its ability in turning into a needed drug in this pandemic.

This review attempts to summarize the MOA of CQ/HCQ and its side effects. The existing literature hints that till date, the role of CQ/HCQ in COVID-19 may be sceptical, and further studies are warranted for obtaining a therapeutic option that could be effectively used across the world to rise out from this pandemic.
Exploiting Latent Semantic Subspaces to Derive Associations for Specific Pharmaceutical Semantics
Authors: Wawrzinek Janus , Pinto José María González , Wiehr Oliver , Balke Wolf-Tilo
Published: August 2020

State-of-the-art approaches in the field of neural embedding models (NEMs) enable progress in the automatic extraction and prediction of semantic relations between important entities like active substances, diseases, and genes. In particular, the prediction property is making them valuable for important research-related tasks such as hypothesis generation and drug repositioning. A core challenge in the biomedical domain is to have interpretable semantics from NEMs that can distinguish, for instance, between the following two situations: (a) drug x induces disease y and (b) drug x treats disease y. However, NEMs alone cannot distinguish between associations such as treats or induces. Is it possible to develop a model to learn a latent representation from the NEMs capable of such disambiguation? To what extent do we need domain knowledge to succeed in the task? In this paper, we answer both questions and show that our proposed approach not only succeeds in the disambiguation task but also advances current growing research efforts to find real predictions using a sophisticated retrospective analysis.
Furthermore, we investigate which type of associations is generally better contextualized and therefore probably has a stronger influence in our disambiguation task. In this context, we present an approach to extract an interpretable latent semantic subspace from the original embedding space in which therapeutic drug–disease associations are more likely
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Harnessing the Power of Quality Assurance Data: Can We Use Statistical Modeling for Quality Risk Assessment of Clinical Trials?
Authors: Koneswarakantha Björn , Ménard Timothé , Rolo Donato , Barmaz Yves , Bowling Rich
Published: August 2020

Background

The increasing number of clinical trials and their complexity make it challenging to detect and identify clinical quality issues timely. Despite extensive sponsor audit programs and monitoring activities, issues related to data integrity, safety, sponsor oversight and patient consent have recurring audit and inspection findings. Recent developments in data management and IT systems allow statistical modeling to provide insights to clinical Quality Assurance (QA) professionals to help mitigate some of the key clinical quality issues more holistically and efficiently.

Methods

We used findings from a curated data set from Roche/Genentech operational and quality assurance study data, covering a span of 8 years (2011–2018) and grouped them into 5 clinical impact factor categories, for which we modeled the risk with a logistic regression using hand crafted features.

Results

We were able to train 5 interpretable, cross-validated models with several distinguished risk factors, many of which confirmed field observations of our quality professionals. Our models were able to reliably predict a decrease in risk by 12–44%, with 2–8 coefficients each, despite a low signal-to-noise ratio in our data set.

Conclusion

We proposed a modeling strategy that could provide insights to clinical QA professionals to help them mitigate key clinical quality issues (e.g., safety, consent, data integrity) in a more sustained data-driven way, thus turning the traditional reactive approach to a more proactive monitoring and alerting approach. Also, we are calling for cross-sponsors collaborations and data sharing to improve and further validate the use of statistical models in clinical QA.