bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards Precision Medicine in Gestational Diabetes: Pathophysiology and Glycemic Patterns in Pregnant Women With Obesity
Authors: White Sara L , Koulman Albert , Ozanne Susan E , Furse Samuel , Poston Lucilla , Meek Claire L
Published: March 2023

Aims

Precision medicine has revolutionized our understanding of type 1 diabetes and neonatal diabetes but has yet to improve insight into gestational diabetes mellitus (GDM), the most common obstetric complication and strongly linked to obesity. Here we explored if patterns of glycaemia (fasting, 1 hour, 2 hours) during the antenatal oral glucose tolerance test (OGTT), reflect distinct pathophysiological subtypes of GDM as defined by insulin secretion/sensitivity or lipid profiles.

Methods

867 pregnant women with obesity (body mass index ≥ 30 kg/m2) from the UPBEAT trial (ISRCTN 89971375) were assessed for GDM at 28 weeks’ gestation (75 g oral glucose tolerance test OGTT; World Health Organization criteria). Lipid profiling of the fasting plasma OGTT sample was undertaken using direct infusion mass spectrometry and analyzed by logistic/linear regression, with and without adjustment for confounders. Insulin secretion and sensitivity were characterized by homeostatic model assessment 2b and 2s, respectively.

Results

In women who developed GDM (n = 241), patterns of glycaemia were associated with distinct clinical and biochemical characteristics and changes to lipid abundance in the circulation. Severity of glucose derangement, rather than pattern of postload glycaemia, was most strongly related to insulin action and lipid abundance/profile. Unexpectedly, women with isolated postload hyperglycemia had comparable insulin secretion and sensitivity to euglycemic women, potentially indicative of a novel mechanistic pathway.

Conclusions

Patterns of glycemia during the OGTT may contribute to a precision approach to GDM as assessed by differences in insulin resistance/secretion. Further research is indicated to determine if isolated postload hyperglycemia reflects a different mechanistic pathway for targeted management.
Assessing trait emotional intelligence and its relationship with stress and health behaviour in the education sector: An empirical study from Uttarakhand, India
Authors: Pandey Mamta , Sharma Deepti , Kamboj NK
Published: March 2023

Background: Emotional intelligence of teachers can affect their mental and physical health as well their performance in school. Both emotional intelligence and health behavior can have an impact on stress. The majority of Indian studies have examined only one type of teacher, have used indigenous scales which are not internationally valid, and have not studied health behaviour. The role of age and gender on emotional intelligence is also a debatable subject which requires larger studies 

The present study was undertaken to evaluate the trait emotional intelligence, stress and health behaviour of teachers and to determine their inter-relationship and to assess the role of demographic and professional attributes on emotional intelligence. 

Methods: Teachers from different schools, colleges and professional institutes situated in Dehradun and nearby towns in the state of Uttarakhand, India were evaluated by internationally valid tools for the three parameters.  

Results:  Emotional Intelligence of teachers has no relation with age, gender, educational qualification, level of teaching or type of institute. It has a negative correlation with stress and a positive correlation with health behaviour. Further, health behaviour is inversely related to stress. 

Conclusions: Assessment of emotional intelligence and health behaviour of teachers should be a part of their routine evaluation and training so that specific interventions to reduce stress and to improve their overall health and performance can be appropriately planned.
Convolutional neural networks for real-time wood plank detection and defect segmentation
Authors: Mohsin Mazhar , Balogun Oluwafemi Samson , Haataja Keijo , Toivanen Pekka
Published: March 2023

Background: Defect detection and segmentation on product surfaces in industry has become one of the most important steps in quality control. There are many sophisticated hardware and software tools used in the industry for this purpose. The need for the real-time classification and detection of defects in industrial quality control has become a crucial requirement. Most algorithms and deep neural network architectures require expensive hardware to perform inference in real-time. This necessitates the design of architectures that are light-weight and suitable for deployment in industrial environments.

Methods: In this study, we introduce a novel method for detecting wood planks on a fast-moving conveyor and using a convolutional neural network (CNN) to segment surface defects in real-time. A backbone network is trained with a large-scale image dataset. A dataset of 5000 images is created with proper annotation of wood planks and defects. In addition, a data augmentation technique is employed to enhance the accuracy of the model. Furthermore, we examine both statistical and deep learning-based approaches to identify and separate defects using the latest methods.

Results: Our plank detection method achieved an impressive mean average precision of 97% and 96% of global pixel accuracy for defect segmentation. This remarkable performance is made possible by the real-time processing capabilities of our system, which can run at 30 frames per second (FPS) without sacrificing accuracy.

Conclusions: The results of our study demonstrate the potential of our method not only in industrial wood processing applications but also in other industries where materials undergo similar processes of defect detection and segmentation. By utilizing our method, these industries can expect to see improved efficiency, accuracy, and overall productivity.
Formation of Healthy and Safe Lifestyle Skills in Younger Schoolchildren
Authors: Artyuhova I.
Published: March 2023

The article emphasizes the urgency of realizing the goal of forming a healthy lifestyle and proper behavior in the environment in primary schoolchildren in accordance with the requirements of the Federal State Educational Standard for Primary General Education (FSES PGE). The continuity and prospects of the content of familiarization of students in grades 1-4 with the rules of safe behavior at home, on the streets and roads, playgrounds, in the natural environment are revealed. The features of the organization of lessons are characterized, in which the formation of the skills and abilities of safe behavior in younger students takes place: a motivational block of methods, a visual-information block, an approximate-evaluating and practical blocks. Specific examples of exercises and tasks of the discussed methodology are given
Modeling Educational Space in a Modern Elementary School
Authors: Solov'ev Ya. , Martynova E.
Published: March 2023

The article discusses the idea of modeling the educational space of a modern elementary school within the framework of the working program of upbringing of an educational organization. A detailed analysis of the main structural components of the Approximate working program of education is given: target, content, organizational. It highlights the targets set out in it, which are formulated in accordance with the updated version of the Federal State Educational Standard for Primary General Education. On this basis, the ways of constructing a working program of education for elementary school are determined.
Improvement of the Educational Process Management System
Authors: Pavlova N. , Borisova M.
Published: March 2023

The article is devoted to the search for the optimal formula of the educational process management system. It is determined that the main condition for providing high-quality education is to increase human resources, providing them with advanced innovative technologies.
Developing Future Teachers’ Research Competence in the Context of the Environmental Approach Implementation
Authors: Bukusheva A. , Pavlova O. , Hudyakova Anna , Chirkova N.
Published: March 2023

The article discusses the environmental approach as the basis for the developing of the future teachers’ research competencies. Research competencies are among the general competencies provided for by the Federal State Educational Standard of Higher Education. Therefore, the problem of training a teacher-researcher is one of the relevant issues of higher education pedagogy. The purpose of the research is to study the dynamics of the formation of  future teachers’ research competencies under the influence of  the university educational environment. As  a result of  a comparative analysis of  the knowledge and skills of students in the field of research activities, a conclusion was made about the influence of the educational environment on the formation of a future teacher’s research position. Summarizing the experience of three regional universities in building the educational environment, its main components were identified (spatial, institutional, programmatic, organizational, content and competitive) are identified.
Intrachoice Dynamics Shape Social Decisions
Authors: Chen Fadong , Zhu Zhi , Shen Qiang , Krajbich Ian , Hare Todd A.
Published: March 2023

Do people have well-defined social preferences waiting to be applied when making decisions? Or do they have to construct social decisions on the spot? If the latter, how are those decisions influenced by the way in which information is acquired and evaluated? These temporal dynamics are fundamental to understanding how people trade off selfishness and prosociality in organizations and societies. Here, we investigate how the temporal dynamics of the choice process shape social decisions in three studies using response times and mouse tracking. In the first study, participants made binary decisions in mini-dictator games with and without time constraints. Using mouse trajectories and a starting time drift diffusion model, we find that, regardless of time constraints, selfish participants were delayed in processing others’ payoffs, whereas the opposite was true for prosocial participants. The independent mouse trajectory and computational modeling analyses identified consistent measures of the delay between considering one’s own and others’ payoffs (self-onset delay, SOD). This measure correlated with individual differences in prosociality and predicted heterogeneous effects of time constraints on preferences. We confirmed these results in two additional studies, one a purely behavioral study in which participants made decisions by pressing computer keys, and the other a replication of the mouse-tracking study. Together, these results indicate that people preferentially process either self or others’ payoffs early in the choice process. The intrachoice dynamics are crucial in shaping social preferences and might be manipulated via nudge policies (e.g., manipulating the display order or saliency of self and others’ outcomes) for behavior in managerial or other contexts.

This paper was accepted by Yan Chen, behavioral economics and decisions analysis.

Funding: F. Chen acknowledges support from the National Natural Science Foundation of China [Grants 71803174 and 72173113]. Z. Zhu acknowledges support from the Ministry of Science and Technology [Grant STI 2030-Major Projects 2021ZD0200409]. Q. Shen acknowledges support from the National Natural Science Foundation of China [Grants 71971199 and 71942004]. I. Krajbich acknowledges support from the U.S. National Science Foundation [Grant 2148982]. This work was also supported by the James McKeen Cattell Fund.

Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2023.4732 .
The registered nursing associate: an overview
Authors: Peate Ian
Published: March 2023

Registered nursing associates have obtained a nursing associate foundation degree that has been endorsed by the Nursing and Midwifery Council (NMC) through an approved educational institution. This usually involves 2 years of higher-level study, enabling the registered nursing associate to undertake more complex and significant tasks than a healthcare assistant would, but without the scope of a registered nurse. It is not the intention to replace the registered nurse with a registered nursing associate. The role is used and regulated in England, with the aim of addressing a skills gap between healthcare assistants/support workers and registered nurses – it can also provide a progression route into graduate-level nursing. This article, the first in a series, provides an overview of the registered nursing associate role.
POSSÍVEL ANALOGIA ENTRE A TERMODINÂMICA E A ELETRICIDADE NO ENSINO MÉDIO
Authors: Bastos Dias Diego Nonato
Published: March 2023

No decorrer do tempo, os educadores de física sempre estão em busca de novas formas de aperfeiçoar o processo de ensino-aprendizagem. Uma dessas formas é por meio da utilização de analogias para tornar os conceitos ensinados mais “reais” para os estudantes. O uso dessa ferramenta didática no âmbito do eletromagnetismo quase sempre tenta relacionar a mecânica de líquidos (como a água) com o movimento de campos elétricos e magnéticos. Portanto, neste trabalho, foi desenvolvida uma nova analogia, que utiliza grandezas termodinâmicas para o ensino de grandezas ligadas à eletricidade. Para verificar uma possível validade do uso dessa analogia, usamos quatro argumentos que utilizam conceitos presentes nos livros didáticos de Gaspar (2016a), Gaspar (2016b), Luz, Alvarez & Guimarães (2016a), Luz, Alvarez & Guimarães (2016b), Biscuola, Bôas & Doca (2016a) e Biscuola, Bôas & Doca (2016b). Tais argumentos também podem ser usados para inspirar professores na sala de aula. Verificamos que a analogia desenvolvida possui alguns pontos interessantes, pois ela permite, por exemplo, que o estudante relacione ciclos termodinâmicos com circuitos elétricos. Porém, ao mesmo tempo, demonstra-se limitada, pois não podemos usá-la para entender grandezas magnéticas ou grandezas vetoriais, como força e campo elétrico.
A DOCÊNCIA UNIVERSITÁRIA EM FÍSICA NO BRASIL: INTERIORIZAÇÃO E PRODUTIVIDADE NAS NOVAS IFES
Authors: Sodré Marques Murilo , Silva Santana Wanisson
Published: March 2023

Neste estudo, com o objetivo de avaliar as consequências da interiorização do ensino superior brasileiro sobre a prática docente, o trabalho de professores universitários de Física de três instituições federais de ensino superior criadas a partir do programa REUNI e que possuem pelo menos um curso de graduação em Física foi analisado quantitativamente nos aspectos relacionados à carga horária didática, a quantidade de disciplinas distintas ministradas e a produção acadêmica. Em que pese a constatação acerca da grande variabilidade média de disciplinas ministradas por estes docentes em um período de cinco anos, principalmente quando comparada à realidade de instituições consolidadas localizadas em grandes centros, não foi possível perceber uma correlação entre carga horária crescente e diminuição da produção acadêmica. Quando analisada a produção docente no período, percebeu-se a sua grande variabilidade, com razões que vão desde a capacidade heterogênea de produção de cada docente, aliado ao fato de haver um corpo docente em formação em nível de doutorado, ou até mesmo a uma estrutura administrativa que demanda jovens pesquisadores exercendo funções administrativas, em detrimento das atividades de pesquisa e extensão. Seja na perspectiva da excelência da docência superior atrelada à pesquisa ou vinculada à uma pedagogia inclusiva, transversal e um tanto quanto subjetiva, a excessiva diversidade de componentes, bem como os altos encargos, impactam ambos os caminhos para a dita excelência e, evidentemente, pode acarretar impactos individuais.
No tempo do Big Ben
Authors: Alves Iron
Published: March 2023

Sobre a Arte:

Numa noite de céu com poucas nuvens em Londres, a lua chega pontualmente e posa para a foto ao lado de um dos relógios mais famosos do planeta.
Boredom in the age of COVID-19: the unsettling dis-ease of late modern life
Authors: Huberman Jenny
Published: March 2023

This article explores how boredom emerged as a central threat to Americans’ sense of well-being in the early days of the COVID-19 pandemic. Drawing upon media coverage from a range of sources, I ask: What do responses to the COVID-19 pandemic reveal more generally about the way boredom has emerged as one of the central dis-eases of modern life? Why has free time become something that increasingly generates intolerable anxiety? In what ways can studying responses to the COVID-19 lockdown help us trace larger transformations in the social construction and subjective experience of time? The article argues that while many Americans experienced boredom as a form of social death engendered by the deroutinising aspects of lockdown life, responses to the COVID-19 pandemic also reveal the way boredom has emerged as a form of psychic alienation permeating the very core of American society. Drawing upon insights from psychoanalytic theory, I will ultimately propose that our dis-ease with free time may be linked to a growing incapacity to fantasise as more and more of our mental lives are colonised by the digital infrastructures and extractive imperatives of our 24/7 society (Crary, 2014).
Dynamically switchable self-focused thermal emission
Authors: Audhkhasi Romil , Qu Yurui , Zhou Ming , Yu Zongfu , Povinelli Michelle L.
Published: March 2023

The ability to manipulate thermal emission is paramount to the advancement of a wide variety of fields such as thermal management, sensing and thermophotovoltaics. In this work, we propose a microphotonic lens for achieving temperature-switchable self-focused thermal emission. By utilizing the coupling between isotropic localized resonators and the phase change properties of VO2, we design a lens that selectively emits focused radiation at a wavelength of 4 µm when operated above the phase transition temperature of VO2. Through direct calculation of thermal emission, we show that our lens produces a clear focal spot at the designed focal length above the phase transition of VO2 while emitting a maximum relative focal plane intensity that is 330 times lower below it. Such microphotonic devices capable of producing temperature-dependent focused thermal emission could benefit several applications such as thermal management and thermophotovoltaics while paving the way for next-generation contact-free sensing and on-chip infrared communication.
Broadband polarization/mode insensitive 3-dB optical coupler for silicon photonic switches
Authors: Xu Heming , Zhang Guowu , Mojaver Kaveh (Hassan) Rahbardar , Liboiron-Ladouceur Odile
Published: March 2023

In this work, we experimentally demonstrate a four-mode polarization/mode insensitive 3-dB coupler based on an adiabatic coupler. The proposed design works for the first two transverse electric (TE) modes and the first two transverse magnetic (TM) modes. Over an optical bandwidth of 70 nm (1500 nm to 1570 nm), the coupler exhibits at most 0.7 dB insertion loss with a maximum crosstalk of -15.7 dB and a power imbalance not worse than 0.9 dB. A multimode photonic switch matrix using this optical coupler is proposed simultaneously exploiting wavelength division multiplexing (WDM), polarization division multiplexing (PDM), and mode division multiplexing (MDM). Based on the coupler experimental measurements, the switching system loss is estimated to be 10.6 dB with crosstalk limited by the MDM (de)multiplexing circuit.
An approach for linear optical phase demodulation using a single photodetector
Authors: Liu Changlin , Zhang Huixing , Wen Aijun , Men Yuan , Wang Shuaikang , Zeng Wei
Published: March 2023

In this paper, we propose and experimentally verify a phase-modulated radio-over-fiber (RoF) link capable of transmitting the radio frequency (RF) signal linearly. By executing the Kramers–Kronig (KK) algorithm at the receiver, the proposed link can accomplish linear optical phase demodulation with a single photodetector rather than a coherent receiver. In the 16-quadrature amplitude modulation (16-QAM) and 64-QAM microwave vector signal transmission experiments, measured error vector magnitudes (EVMs) are 4.14% and 4.38%, respectively, after 25-km fiber transmission, and the measured spurious-free dynamic range (SFDR) is 114.5 dB·Hz2/3, which shows a good performance in linearity.
A systematic evaluation of deep learning methods for the prediction of drug synergy in cancer
Authors: Baptista Delora , Ferreira Pedro G. , Rocha Miguel
Published: March 2023

One of the main obstacles to the successful treatment of cancer is the phenomenon of drug resistance. A common strategy to overcome resistance is the use of combination therapies. However, the space of possibilities is huge and efficient search strategies are required. Machine Learning (ML) can be a useful tool for the discovery of novel, clinically relevant anti-cancer drug combinations. In particular, deep learning (DL) has become a popular choice for modeling drug combination effects. Here, we set out to examine the impact of different methodological choices on the performance of multimodal DL-based drug synergy prediction methods, including the use of different input data types, preprocessing steps and model architectures. Focusing on the NCI ALMANAC dataset, we found that feature selection based on prior biological knowledge has a positive impact—limiting gene expression data to cancer or drug response-specific genes improved performance. Drug features appeared to be more predictive of drug response, with a 41% increase in coefficient of determination (R2) and 26% increase in Spearman correlation relative to a baseline model that used only cell line and drug identifiers. Molecular fingerprint-based drug representations performed slightly better than learned representations—ECFP4 fingerprints increased R2 by 5.3% and Spearman correlation by 2.8% w.r.t the best learned representations. In general, fully connected feature-encoding subnetworks outperformed other architectures. DL outperformed other ML methods by more than 35% (R2) and 14% (Spearman). Additionally, an ensemble combining the top DL and ML models improved performance by about 6.5% (R2) and 4% (Spearman). Using a state-of-the-art interpretability method, we showed that DL models can learn to associate drug and cell line features with drug response in a biologically meaningful way. The strategies explored in this study will help to improve the development of computational methods for the rational design of effective drug combinations for cancer therapy.
In vitro–in silico correlation of three-dimensional turbulent flows in an idealized mouth-throat model
Authors: Nof Eliram , Bhardwaj Saurabh , Koullapis Pantelis , Bessler Ron , Kassinos Stavros , Sznitman Josué
Published: March 2023

There exists an ongoing need to improve the validity and accuracy of computational fluid dynamics (CFD) simulations of turbulent airflows in the extra-thoracic and upper airways. Yet, a knowledge gap remains in providing experimentally-resolved 3D flow benchmarks with sufficient data density and completeness for useful comparison with widely-employed numerical schemes. Motivated by such shortcomings, the present work details to the best of our knowledge the first attempt to deliver in vitro–in silico correlations of 3D respiratory airflows in a generalized mouth-throat model and thereby assess the performance of Large Eddy Simulations (LES) and Reynolds-Averaged Numerical Simulations (RANS). Numerical predictions are compared against 3D volumetric flow measurements using Tomographic Particle Image Velocimetry (TPIV) at three steady inhalation flowrates varying from shallow to deep inhalation conditions. We find that a RANS k-ω SST model adequately predicts velocity flow patterns for Reynolds numbers spanning 1’500 to 7’000, supporting results in close proximity to a more computationally-expensive LES model. Yet, RANS significantly underestimates turbulent kinetic energy (TKE), thus underlining the advantages of LES as a higher-order turbulence modeling scheme. In an effort to bridge future endevours across respiratory research disciplines, we provide end users with the present in vitro–in silico correlation data for improved predictive CFD models towards inhalation therapy and therapeutic or toxic dosimetry endpoints.
New workflow predicts drug targets against SARS-CoV-2 via metabolic changes in infected cells
Authors: Leonidou Nantia , Renz Alina , Mostolizadeh Reihaneh , Dräger Andreas
Published: March 2023

COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets’ inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.
Theta-gamma phase amplitude coupling in a hippocampal CA1 microcircuit
Authors: Ponzi Adam , Dura-Bernal Salvador , Migliore Michele
Published: March 2023

Phase amplitude coupling (PAC) between slow and fast oscillations is found throughout the brain and plays important functional roles. Its neural origin remains unclear. Experimental findings are often puzzling and sometimes contradictory. Most computational models rely on pairs of pacemaker neurons or neural populations tuned at different frequencies to produce PAC. Here, using a data-driven model of a hippocampal microcircuit, we demonstrate that PAC can naturally emerge from a single feedback mechanism involving an inhibitory and excitatory neuron population, which interplay to generate theta frequency periodic bursts of higher frequency gamma. The model suggests the conditions under which a CA1 microcircuit can operate to elicit theta-gamma PAC, and highlights the modulatory role of OLM and PVBC cells, recurrent connectivity, and short term synaptic plasticity. Surprisingly, the results suggest the experimentally testable prediction that the generation of the slow population oscillation requires the fast one and cannot occur without it.
Mitochondrial network structure controls cell-to-cell mtDNA variability generated by cell divisions
Authors: Glastad Robert C. , Johnston Iain G.
Published: March 2023

Mitochondria are highly dynamic organelles, containing vital populations of mitochondrial DNA (mtDNA) distributed throughout the cell. Mitochondria form diverse physical structures in different cells, from cell-wide reticulated networks to fragmented individual organelles. These physical structures are known to influence the genetic makeup of mtDNA populations between cell divisions, but their influence on the inheritance of mtDNA at divisions remains less understood. Here, we use statistical and computational models of mtDNA content inside and outside the reticulated network to quantify how mitochondrial network structure can control the variances of inherited mtDNA copy number and mutant load. We assess the use of moment-based approximations to describe heteroplasmy variance and identify several cases where such an approach has shortcomings. We show that biased inclusion of one mtDNA type in the network can substantially increase heteroplasmy variance (acting as a genetic bottleneck), and controlled distribution of network mass and mtDNA through the cell can conversely reduce heteroplasmy variance below a binomial inheritance picture. Network structure also allows the generation of heteroplasmy variance while controlling copy number inheritance to sub-binomial levels, reconciling several observations from the experimental literature. Overall, different network structures and mtDNA arrangements within them can control the variances of key variables to suit a palette of different inheritance priorities.
Modulating the Kynurenine pathway or sequestering toxic 3-hydroxykynurenine protects the retina from light-induced damage in Drosophila
Authors: Hebbar Sarita , Traikov Sofia , Hälsig Catrin , Knust Elisabeth
Published: March 2023

Tissue health is regulated by a myriad of exogenous or endogenous factors. Here we investigated the role of the conserved Kynurenine pathway (KP) in maintaining retinal homeostasis in the context of light stress inDrosophila melanogaster.cinnabar,cardinalandscarletare fly genes that encode different steps in the KP. Along withwhite, these genes are known regulators of brown pigment (ommochrome) biosynthesis. Usingwhiteas a sensitized genetic background, we show that mutations incinnabar,cardinalandscarletdifferentially modulate light-induced retinal damage. Mass Spectrometric measurements of KP metabolites in flies with different genetic combinations support the notion that increased levels of 3-hydroxykynurenine (3OH-K) and Xanthurenic acid (XA) enhance retinal damage, whereas Kynurenic Acid (KYNA) and Kynurenine (K) are neuro-protective. This conclusion was corroborated by showing that feeding 3OH-K results in enhanced retinal damage, whereas feeding KYNA protects the retina in sensitized genetic backgrounds. Interestingly, the harmful effects of free 3OH-K are diminished by its sub-cellular compartmentalization. Sequestering of 3OH-K enables the quenching of its toxicity through conversion to brown pigment or conjugation to proteins. This work enabled us to decouple the role of these KP genes in ommochrome formation from their role in retinal homeostasis. Additionally, it puts forward new hypotheses on the importance of the balance of KP metabolites and their compartmentalization in disease alleviation.
Lessons from 20 years of medical cannabis use in Canada
Authors: Shim Minsup , Nguyen Hai , Grootendorst Paul
Published: March 2023

Background

Canada was one of the first countries to regulate the medical use of cannabis. However, literature on Canada’s medical cannabis program is limited.

Methods

We use administrative data from the medical cannabis program, and licensed cannabis vendor catalog data to describe a) the participation of patients, physicians, and cannabis vendors in the program from its inception in 1999 to 2021, and b) trends in medical cannabis consumption, prices and potency. We also use national surveys conducted over the last several decades to estimate trends in regular cannabis use (medical or otherwise) and how it changed during the medical cannabis access regimes.

Results

In 2001, the Canadian government granted access to those with physician-documented evidence of a severe health problem that could not be managed using conventional therapies. Most patients accessed cannabis grown under a personal production license. By 2013, authorized daily cannabis dosages were very high. In 2014, the government, concerned over illegal diversion, required that cannabis be purchased from a licensed commercial grower; personal production was banned. Physicians were given responsibility for authorizing patient access. To fill the regulatory void, the physician regulatory bodies in Canada imposed their own prescribing restrictions. After these changes, the number of physicians who were willing to support patient cannabis use markedly decline but the number of patients participating in the program sharply increased. Medical cannabis use varied by province–rates were generally lower in provinces with stricter regulations on physician cannabis prescribing. Most varieties of cannabis oil available for sale are now high in CBD and low in THC. Dry cannabis varieties, conversely, tend to be high in THC and low in CBD. Inflation adjusted prices of most varieties of medical cannabis have declined over time. We find that rates of daily cannabis use (medical or otherwise) increased markedly after the 2014 policy regime. The fraction of Canadians using cannabis daily increased again after the 2018 legalization of recreational cannabis; at the same time, participation in the medical access program declined.

Conclusion

The implications for patient health outcomes of changes in the medical cannabis program and legalization of recreational use remains an important area for future research.
Characteristics, clinical outcomes, and mortality of older adults living with HIV receiving antiretroviral treatment in the sub-urban and rural areas of northern Thailand
Authors: Aurpibul Linda , Sripan Patumrat , Paklak Wason , Tangmunkongvorakul Arunrat , Rerkasem Amaraporn , Rerkasem Kittipan , Srithanaviboonchai Kriengkrai
Published: March 2023

Since the introduction of antiretroviral treatment (ART), people living with HIV worldwide live into older age. This observational study described the characteristics, clinical outcomes, and mortality of older adults living with HIV (OALHIV) receiving ART from the National AIDS program in northern Thailand. Participants aged ≥ 50 years were recruited from the HIV clinics in 12 community hospitals. Data were obtained from medical records and face-to-face interviews. In 2015, 362 OALHIV were enrolled; their median (interquartile range) age and ART duration were 57 years (54–61), and 8.8 years (6.4–11.2), respectively. At study entry, 174 (48.1%) had CD4 counts ≥ 500 cells/mm3; 357 of 358 (99.6%) with available HIV RNA results were virologic-suppressed. At the year 5 follow-up, 39 died, 11 were transferred to other hospitals, 3 were lost to follow-up, and 40 did not contribute data for this analysis, but remained in care. Among the 269 who appeared, 149 (55%) had CD4 counts ≥ 500 cells/mm3, and 227/229 tested (99%) were virologic-suppressed. The probability of 5-year overall survival was 89.2% (95% confidence interval, CI 85.4–92.1%). A significantly low 5-year overall survival (66%) was observed in OALHIV with CD4 counts < 200 cells/mm3 at study entry. The most common cause of death was organ failure in 11 (28%), followed by malignancies in 8 (21%), infections in 5 (13%), mental health-related conditions in 2 (5%), and unknown in 13 (33%). In OALHIV with stable HIV treatment outcomes, mortality from non-infectious causes was observed. Monitoring of organ function, cancer surveillance, and mental health screening are warranted.
Estimation of poverty bounds for Pakistan using synthetic panel data
Authors: Shabnam Nadia , Ameer Waqar , Aurangzeb Neelam , Ashraf Muhammad Azeem , Shah Syed Hasanat
Published: March 2023

Poverty is a big threat to prosperity in developing countries like Pakistan. Alleviating poverty needs concerted efforts including how to measure and analyze poverty. Therefore, this paper employs synthetic panel technique and uses repeated cross-sections household survey dataset (Household Integrated and Economic Survey (HIES)) of Pakistan for 2010–11 and 2015–16, to derive poverty bounds for Pakistan. The findings of the paper suggest that 17% of population still remains in poverty in 2015–16 as they were in 2010–11. They don’t move in or out of poverty. In the same periods 19% population affected by poverty. The 2.5% poor’s of 2010–11 moves out of poverty in 2015–16. This constitutes the first attempt to provide an insight into poverty dynamics in Pakistan using the available survey data.
Both trust in, and polarization of trust in, relevant sciences have increased through the COVID-19 pandemic
Authors: Radrizzani Sofia , Fonseca Cristina , Woollard Alison , Pettitt Jonathan , Hurst Laurence D.
Published: March 2023

While attempts to promote acceptance of well-evidenced science have historically focused on increasing scientific knowledge, it is now thought that for acceptance of science, trust in, rather than simply knowledge of, science is foundational. Here we employ the COVID-19 pandemic as a natural experiment on trust modulation as it has enabled unprecedented exposure of science. We ask whether trust in science has on the average altered, whether trust has changed the same way for all and, if people have responded differently, what predicts these differences? We 1) categorize the nature of self-reported change in trust in “scientists” in a random sample of over 2000 UK adults after the introduction of the first COVID vaccines, 2) ask whether any reported change is likely to be real through consideration of both a negative control and through experiment, and 3) address what predicts change in trust considering sex, educational attainment, religiosity, political attitude, age and pre-pandemic reported trust. We find that many more (33%) report increased trust towards “scientists” than report decreased trust (7%), effects of this magnitude not being seen in negative controls. Only age and prior degree of trust predict change in trust, the older population increasing trust more. The prior degree of trust effect is such that those who say they did not trust science prior to the pandemic are more likely to report becoming less trusting, indicative of both trust polarization and a backfire effect. Since change in trust is predictive of willingness to have a COVID-19 vaccine, it is likely that these changes have public health consequences.
Examining the role of moral, emotional, behavioural, and personality factors in predicting online shaming
Authors: Muir Shannon Raine , Roberts Lynne Diane , Sheridan Lorraine , Coleman Amy Ruth
Published: March 2023

Online shaming, where people engage in social policing by shaming perceived transgressions via the internet, is a widespread global phenomenon. Despite its negative consequences, scarce research has been conducted and existing knowledge is largely anecdotal. Using a correlational online survey, this mixed-method study firstly assessed whether moral grandstanding, moral disengagement, emotional reactivity, empathy, social vigilantism, online disinhibition, machiavellianism, narcissism, and psychopathy predict participants’ (N = 411; aged 15–78) likelihood to engage in online shaming. Two hierarchical multiple regression analyses revealed these predictors significantly accounted for 39% of variance in online shaming intentions, and 20% of variance in perceived deservedness of online shaming (f2 = .25 and .64 respectively, p < .001). A content analysis of an open-ended question offered further insights into public opinions about online shaming. These qualitative findings included the perception of online shaming as a form of accountability, the perceived destructive effects of online shaming, the perceived role of anonymity in online shaming, online shaming as a form of entertainment, online shaming involving ‘two sides to every story’, the notion that ‘hurt people hurt people’, online shaming as now a social norm, and the distinction between the online shaming of public and private figures. These findings can be used to inform the general public and advise appropriate responses from service providers and policy makers to mitigate damaging impacts of this phenomenon.
Efficacy of continuous positive airway pressure on TNF-α in obstructive sleep apnea patients: A meta-analysis
Authors: Luo Yong , Zhang Fa-Rong , Wu Jun-Lin , Jiang Xi-Jiao
Published: March 2023

Background

Tumor necrosis factor-α (TNF-α) is an important mediator of the immune response. At present, the improvement of TNF-α after continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) is still controversial.

Methods

We conducted a systematic review of the present evidence based on a meta-analysis to elucidate the effects of TNF-α on OSAHS after CPAP treatment.

Results

To measure TNF-α, ten studies used enzyme-linked immunosorbent assay (ELISA), and one used radioimmunoassay. The forest plot outcome indicated that CPAP therapy would lower the TNF-α levels in OSAHS patients, with a weighted mean difference (WMD) of 1.08 (95% CI: 0.62–1.55; P < 0.001) based on the REM since there is highly significant heterogeneity (I2 = 90%) among the studies. Therefore, we used the subgroup and sensitivity analyses to investigate the source of heterogeneity. The findings of the sensitivity analysis revealed that the pooled WMD ranged from 0.91 (95% CI: 0.52–1.31; P < 0.001) to 1.18 (95% CI: 0.74–1.63; P < 0.001). The findings were not influenced by any single study. Notably, there was homogeneity in the Asia subgroup and publication year: 2019, implying that these subgroups could be the source of heterogeneity.

Conclusion

Our meta-analysis recommends that CPAP therapy will decrease the TNF-α level in OSAHS patients, but more related research should be conducted.
Exploring genome gene content and morphological analysis to test recalcitrant nodes in the animal phylogeny
Authors: Juravel Ksenia , Porras Luis , Höhna Sebastian , Pisani Davide , Wörheide Gert
Published: March 2023

An accurate phylogeny of animals is needed to clarify their evolution, ecology, and impact on shaping the biosphere. Although datasets of several hundred thousand amino acids are nowadays routinely used to test phylogenetic hypotheses, key deep nodes in the metazoan tree remain unresolved: the root of animals, the root of Bilateria, and the monophyly of Deuterostomia. Instead of using the standard approach of amino acid datasets, we performed analyses of newly assembled genome gene content and morphological datasets to investigate these recalcitrant nodes in the phylogeny of animals. We explored extensively the choices for assembling the genome gene content dataset and model choices of morphological analyses. Our results are robust to these choices and provide additional insights into the early evolution of animals, they are consistent with sponges as the sister group of all the other animals, the worm-like bilaterian lineage Xenacoelomorpha as the sister group of the other Bilateria, and tentatively support monophyletic Deuterostomia.
Information flow among stocks, bonds, and convertible bonds
Authors: Jo Kihwan , Choi Gahyun , Jeong Jongwook , Ahn Kwangwon
Published: March 2023

This study examines the information flow between convertible bonds (CBs) and other investment assets, such as stocks and bonds. In particular, we employ transfer entropy (TE) as a proxy for the causal effect between the two assets considering that one of the most widely used methods, Granger causality, requires strict assumptions. When adopting TE, we find that asymmetric information flow arising between assets depends on macroeconomic phases. The stock and bond markets affected the CB market prior to and during the global financial crisis, respectively. In the post-crisis period, we find no meaningful information exchange between CBs and other investment assets concerning their return series. However, we observe a significant cause–effect relationship between CBs and stocks in the rise–fall patterns of their price series. The findings suggest that the appearance of one-directional information flow depends on macroeconomic conditions and the level of data, for example, return series or price fluctuations. Accordingly, investors could exploit this pattern predictability in their portfolio management. In addition, policymakers must closely monitor the information flow among the three markets. When any two markets exchange information in a state of strong market integration, unbalanced regulation between them could lead to market distortions and regulatory arbitrage.
The f0 perturbation effects in focus marking: Evidence from Korean and Japanese
Authors: Chen Si , Hong Yitian , Li Bei , Chun Eunjin
Published: March 2023

Many studies showed that prosodic cues such as f0, duration and intensity are used in focus marking cross-linguistically. Usually, on-focus words exhibit expansions of acoustic cues such as f0 expansion, whereas post-focus words may show compression of acoustic cues. However, how features in a sub-syllabic level are employed in focus marking remain to be investigated. F0 perturbation refers to the phenomenon that vocal folds vibration is affected by the preceding non-sonorant consonant. The current study aims to examine how f0 perturbation is realized in focus marking in two languages Japanese and Korean. Tokyo Japanese is a pitch-accent language and Seoul Korean is considered to be at the stage of quasi-tonogenesis. Our results showed that f0 perturbation effects were enhanced in on-focus positions and compressed in pre- and post-focus positions for both narrow and contrastive focus in both languages. In addition, our results showed that pitch accent can also affect the realization of f0 perturbation in various focus conditions. Compared to Korean, our results in Japanese showed that f0 perturbation effects were less restricted. These results provide new insights into the current model of communicative functions that sub-syllabic level acoustic cues such as f0 perturbation can also be employed in focus marking.
Clinical sensitivity and specificity of a high-throughput microfluidic nano-immunoassay combined with capillary blood microsampling for the identification of anti-SARS-CoV-2 Spike IgG serostatus
Authors: Michielin Grégoire , Arefi Fatemeh , Puhach Olha , Bellon Mathilde , Sattonnet-Roche Pascale , L’Huillier Arnaud G. , Eckerle Isabella , Meyer Benjamin , Maerkl Sebastian J.
Published: March 2023

Objectives

We evaluate the diagnostic performance of dried blood microsampling combined with a high-throughput microfluidic nano-immunoassay (NIA) for the identification of anti-SARS-CoV-2 Spike IgG seropositivity.

Methods

We conducted a serological study among 192 individuals with documented prior SARS-CoV-2 infection and 44 SARS-CoV-2 negative individuals. Participants with prior SARS-CoV-2 infection had a long interval of 11 months since their qRT-PCR positive test. Serum was obtained after venipuncture and tested with an automated electrochemiluminescence anti-SARS-CoV-2 S total Ig reference assay, a commercial ELISA anti-S1 IgG assay, and the index test NIA. In addition, 109 participants from the positive cohort and 44 participants from the negative cohort participated in capillary blood collection using three microsampling devices: Mitra, repurposed glucose test strips, and HemaXis. Samples were dried, shipped by regular mail, extracted, and measured with NIA.

Results

Using serum samples, we achieve a clinical sensitivity of 98·33% and specificity of 97·62% on NIA, affirming the high performance of NIA in participants 11 months post infection. Combining microsampling with NIA, we obtain a clinical sensitivity of 95·05% using Mitra, 61·11% using glucose test strips, 83·16% using HemaXis, and 91·49% for HemaXis after automated extraction, without any drop in specificity.

Discussion

High sensitivity and specificity was demonstrated when testing micro-volume capillary dried blood samples using NIA, which is expected to facilitate its use in large-scale studies using home-based sampling or samples collected in the field.