bluuebunny/crossref_metadata_2025 huggingface dataset:
Communicative health literacy with physicians in healthcare services– results of a Hungarian nationwide survey
Authors: Israel Frederico Epalanga Albano , Vincze Ferenc , Ádány Róza , Bíró Éva
Published: January 2025

Background

In an efficient and effective healthcare delivery, good communication plays an essential role. The communicative health literacy (COMM-HL) of the patients is an important attribute, but the number of validated COMM-HL assessment tools is low, and they do not cover all aspects of COMM-HL. That’s why a new scale has been developed within an international collaboration. Our aims are to check the measurement properties of the Hungarian version of this COMM-HL questionnaire, to describe the COMM-HL of the Hungarian adult population and to investigate its determinants.

Methods

A total of 1205 adults completed the telephone interview in 2020 as part of the European Health Literacy Population Survey 2019–2021. The questionnaire included items on sociodemographic data, self-perceived health, social support and COMM-HL. The questionnaire’s measurement properties were assessed using Cronbach’s alpha, Spearman-Brown, and item-total correlation coefficients, while the construct validity was investigated with principal component (PCA) and confirmatory factor analysis. The determinants of the COMM-HL were investigated by linear regression.

Results

Both the value of Cronbach’s alpha and the Spearman-Brown correlation were 0.87. The items belonged to one factor and 62.2% of the total variation was explained by this factor based on the PCA. The fit indices indicated that the one-factor structure of the six-item questionnaire exhibited a good fit for the data. The mean score on the COMM-HL scale was 86.8. The easiest task was explaining health concerns while getting enough time in the consultation was rated as the most difficult one. COMM-HL was lower among females, while it was higher among people aged 66–75 years (compared with 18–25 years), those with greater social support and those without financial deprivation.

Conclusions

The questionnaire can be characterized with good internal consistency and the structure of the COMM-HL questionnaire was best explained as a one factor model. In consultations with patients, the effectiveness of communication should be improved, so that patients do not feel that there is not enough time for consultation. At-risk groups with low COMM-HL need special attention during the interactions and the role of social support has to be clarified, too.
The Neuroendocrine Regulation of Reproductive Behavior and Emotional Control by Kisspeptin
Authors: Mills Edouard G , Tsoutsouki Jovanna , Pierret Aureliane C S , Comninos Alexander N , Dhillo Waljit S
Published: January 2025

Reproductive success and ultimately species survival at a population level is contingent on a plethora of neuroendocrine signals working in concert to regulate gonadal function and reproductive behavior. Among these, the neuropeptide kisspeptin (encoded by the KISS1/Kiss1 gene) has emerged as the master regulator of the hypothalamic-pituitary-gonadal axis. Besides the hypothalamus, both kisspeptin and its cognate receptor are extensively expressed throughout cortico-limbic brain structures in rodents and humans, which are regions traditionally implicated in behavioral and emotional responses. Thus, there exists a neuroanatomical framework through which kisspeptin can integrate reproductive behavior and emotional regulation with the reproductive axis. Accordingly, this sets the scene for recent findings derived from an assortment of species, including humans, unveiling kisspeptin as an important gatekeeper of reproductive behavior and emotional control. Herein, we summarize the major preclinical animal and human experimental evidence identifying kisspeptin as a key neuromodulator of reproductive behavior and emotional state. Such findings have laid the foundations for clinical applications of kisspeptin-based therapies for patients with related reproductive and psychosexual disorders.
Regulation of mitochondrial cristae organization by Myo19, Miro1/2 and Metaxin 3
Authors: Shembekar Samruddhi S. , Nikolaus Petra , Honnert Ulrike , Höring Marcus , Attia Aya , Topp Karin , Lohmann Birgit , Liebisch Gerhard , Bähler Martin
Published: January 2025

The actin-based motor myosin-19 (Myo19) exerts force on mitochondrial membrane receptors Miro1/2, influencing endoplasmic reticulum (ER)-mitochondria contact sites and mitochondrial cristae structure. The Mitochondrial Intermembrane Bridging (MIB) complex connects the outer and inner mitochondrial membranes at the cristae junction through the MICOS system. However, the interaction between Myo19, Miro1/2, and the MIB/MICOS complex in cristae regulation remains unclear. This study investigates the roles of Miro1/2 and metaxin 3 (Mtx3), a MIB complex component, in linking Myo19 to MIB/MICOS. We show that Miro1/2 interact with Myo19 and the MIB complex, but not with Mtx3. Their mitochondrial membrane anchors are not essential for MIB interaction or cristae structure. However, Mtx3 is crucial for Myo19 and Miro1/2's connection to MIB/MICOS. Deleting Miro1/2 mimics Myo19 deficiency effects on ER-mitochondria contacts and cristae structure, while Mtx3 deletion does not. Notably, the loss of Myo19 and Miro1/2 alters mitochondrial lipid composition, reducing cardiolipin and its precursors, suggesting Myo19 and Miro1/2 influence cristae indirectly via lipid transfer at ER-mitochondria contact sites.
Start-Up Costs and Market Power: Lessons from the Renewable Energy Transition
Authors: Jha Akshaya , Leslie Gordon
Published: January 2025

Firms expect to recover the fixed costs required to start production by earning positive operating profits in subsequent periods. We develop a dynamic competitive benchmark that accounts for start-up costs, showing that static markups overstate the rents attributable to market power in an electricity market where generators frequently stop and start production in response to rooftop solar output. We demonstrate that the large-scale expansion of solar capacity can lead to increases in the collective profitability of fossil fuel plants because competition softens at sunset—plants displaced by solar during the day must incur start-up costs to compete in the evening. (JEL D24, L13, L25, L94, Q41, Q42)
Political Social Learning: Short-Term Memory and Cycles of Polarization
Authors: Levy Gilat , Razin Ronny
Published: January 2025

This paper investigates the effect of voters’ short-term memory on political outcomes by considering politics as a collective learning process. We find that short-term memory may lead to cycles of polarization and consensus across parties’ platforms. Following periods of party consensus, short-term memory implies that there is little variation in voters’ data and therefore limited information about the true state of the world. This in turn allows parties to further their own interests and hence polarize by offering different policies. In contrast, periods of polarization and turnover involve sufficient variation in the data that allows voters to be confident about what the correct policy is, forcing both parties to offer this policy. (JEL D72, D83, E61)
Research on the Challenges and Approaches to Family Inheritance of Ethnic Traditional Sports Culture
Authors: Jiang Caixia , Xia Siyong , Qin Hao
Published: January 2025

Through the comprehensive use of literature, fieldwork, interviews, questionnaires, data analysis, logical reasoning and other methods, the study takes Shizhu County, Chongqing Municipality, one of the Tujia settlements in China, as an example to sort out the dilemmas that families currently face in the transmission of ethnic traditional sports culture, and to analyze the factors that lead to the dilemmas in the transmission of ethnic traditional sports culture. The results of the study show that there are the following dilemmas in the family inheritance of ethnic traditional sports culture in Shizhu County: alienation of children's ethnic traditional sports culture capital acquisition; lack of family integration of ethnic traditional sports culture; misunderstanding of the family's joint participation in ethnic traditional sports activities; lack of the main body of cultural inheritance, intergenerational inheritance stagnation; and lack of self-awareness of ethnic traditional sports culture. Based on the results of research on the relationship between the family environment and the inheritance of traditional ethnic sports culture, several experiences and insights have been presented: Strengthen the national cultural identity and establish the correct beliefs of parents; pay attention to the transformation of family capital and optimize the structure of capital distribution; create a supportive behavioral environment in the family to enhance the interaction between parents and children; promote the creation of the physical environment of traditional national sports and the precise implementation of the ground; integrate into classroom teaching and promote the "feeding" inheritance; strengthen social guidance to enhance the awareness of national sports; strengthen the platform construction to enhance the cultural atmosphere of traditional national sports. Integrate into classroom teaching to promote "feeding" inheritance; strengthen social guidance to enhance the awareness of national sports; and strengthen platform construction to enhance the cultural atmosphere of national traditional sports.
Successfully starting orthodontic specialty training
Authors: Gray Emily , Bradley Beth , Adam Naeem
Published: January 2025

This article provides a comprehensive guide for new orthodontic trainees, outlining essential strategies to succeed in specialty training. It emphasizes the importance of building professional relationships with peers, supervisors and staff, cultivating high-quality patient records and ensuring a well-rounded training experience. Key topics include managing training commitments, maintaining accurate case logbooks, understanding assessment requirements, and navigating complex treatment modalities. Additionally, the article discusses the benefits of pursuing a higher degree and the importance of balancing work commitments with personal wellbeing. With practical advice, this guide aims to help trainees approach orthodontic training effectively, and maintain a sustainable work–life balance.

CPD/Clinical Relevance: A comprehensive guide designed for new orthodontic trainees, detailing key strategies for successfully navigating specialty training.
Múltiplas interpretações de um poema de química através do dialogismo
Authors: Matos Natália , Batista Vilar Artur , Barbosa-Lima Maria da Conceição
Published: January 2025

Neste trabalho, sugerimos um conjunto de palavras ou expressões para preencher as lacunas do poema “Químico Apaixonado”, de Wilmo Ernesto Francisco Junior. Discutimos as possibilidades de preenchimento, lacuna por lacuna, ao mesmo tempo que explicamos brevemente os conceitos químicos envolvidos. Os conteúdos explorados são: reações de combustão, nox, reações de oxirredução, ressonância e modelos atômicos. Cada espaço vazio pode ser completado de infinitas maneiras, pois depende do modo como o leitor interage com o poema. Partimos do pressuposto de que o leitor dialoga com a poesia e tem uma compreensão ativa dela. A criatividade e vivências de cada um são o que influenciará a escolha das palavras que podem preencher as lacunas. Para enriquecer a discussão, foram utilizadas as teorias das treze categorias cognitivas e da metaformação. Uma resposta ao escrito inicial foi feita em forma de outro poema, com termos químicos, acrescentando os conceitos de reação de decomposição e radioatividade. A conversa aqui estabelecida poderá aprimorar o ensino de química, de maneira a aproveitar o conhecimento prévio do educando em uma possível aplicação do poema em sala de aula.
Almanaque e sequência didática: proposições didáticas para o ensino sobre meteoritos
Authors: Souza Santos Jenivaldo , Freitas Paim Ana Verena , De Lima Ribeiro Carlos Alberto
Published: January 2025

O presente artigo resulta de dois produtos da pesquisa "Entre-laçando representações sociais e saberes científicos sobre meteoritos para uma aprendizagem significativa no Ensino Médio". Foi desenvol-vida no Programa de Pós-Graduação em Astronomia da Universidade Estadual de Feira de Santana. Diante da necessidade de popularizar a Ciência, tornando os meteoritos algo significativo, desenvolvemos e aplicamos uma Sequência Didática (SD) com 30 alunos do Ensino Médio, no Colégio Estadual Democrático Prof. Rômulo Galvão, em Elísio Medrado. Utilizamos como bases teóricas e metodológicas, a Teoria da Aprendizagem Significativa de Ausubel, as Representações Sociais de Moscovici, Núcleo Central das Representações, de Abric e os trabalhos de Zucolotto (2013) e W. Carvalho (2018). Após a aplicação da SD, constatamos que 57% dos alunos alcançaram mais de 50% de acertos, índice muito satisfatório, se comparado aos resultados anterio-res de 3% de alunos que acertaram mais de 50% das questões. Também foi elaborado o Almanaque Meteorítico, disponibilizado gratuitamente, na internet.
Non-intrusive questions with matrix ' dali ' in Bulgarian
Authors: Simeonova Vesela , Kamali Beste
Published: January 2025

abstract: This paper provides novel insights into the meaning of the particles li and dali used in matrix polar questions in Bulgarian. The primary data source is a corpus of an online chat by five family members created for the purposes of this paper. The main finding is that the two particles give rise to two different types of questions: matrix li questions are canonical, information seeking questions. Matrix dali questions, on the other hand, are non-canonical questions which we identify as non-intrusive questions in the sense of Farkas (2022) and analyze in the Table framework of Farkas & Bruce (2010).
Feeling Fictional: Metalepsis, Caprice, and the Uncanny in E. T. A. Hoffmann's "The Sandman"
Authors: Codr Dwight
Published: January 2025

ABSTRACT: The transgression of the boundary between narrative levels—metalepsis—is frequently understood in terms of narrators entering the diegesis, but it can also describe a seeming impossibility: the movement of a character into the author's world. This essay explores the nature and affordances of metalepsis of this latter type—"character metalepsis"—and suggests that it offers a unique sense of what it means to "feel fictional." The feeling of fiction is shown to be closely aligned with paranoia and alienation as characters who seek such passage naturally have a sense of powerlessness and doubts about the source of their consciousness. Drawing on narrative theory and contextualizing metalepsis in Romantic aesthetics, this essay presents a new reading of E. T. A. Hoffmann's quintessential tale of paranoia, "The Sandman" (1816), revealing Hoffmann to have been interested in exploring the feelings of fictional characters—much as he was interested in the feelings of other non-human entities. Under this reading, the essay moves to reconcile the competing views of Freud and Jentsch (who famously disagreed over "Sandman") on the nature of the uncanny. Framed by reflections on the simulation hypothesis and conspiracy theory, the essay suggests that "character metalepsis" provides insight into a wide array of cultural and textual environments.
Nonvolatile switchable dual-functional THz metamaterial with selective transmission and adjustable absorption empowered by q-BICs
Authors: Zhou Lei , Hong Wei , Lv Changgui , Chen Zhaofu , Shen Changsheng , Fan Hehong , Wang Qilong , Bai Ningfeng
Published: January 2025

The integration of tunable characteristics and dual functions into a single terahertz (THz) metamaterial is quickly becoming a major focus of research. This paper presents a nonvolatile switchable dual-functional THz metamaterial with selective transmission and adjustable absorption based on quasi-bound states in the continuum (q-BICs), where the q-BICs are achieved through periodically arranged silicon disks tetramer. By introducing asymmetry perturbation through manipulating the radii of diagonal silicon disks of the proposed THz metamaterial, resulting in the transition from symmetry-protected bound states in the continuum (SP-BICs) to q-BICs. When the middle layer Ge2Sb2Te5 (GST) is in the amorphous state, selective transmission is achieved, which can be applied as a bandstop filter. Additionally, by transforming the phase of GST into the crystalline state in the way of heating, the proposed THz metamaterial behaves as an adjustable absorber due to the generations of q-BICs and Fabry-Pérot resonance (FPR) mode. Multipole decomposition and temporal coupled-mode theory (CMT) are applied to explain the underlying physics. Our work provides valuable insights into the integration of the nonvolatile switchable and dual-functional THz metamaterials empowered by q-BICs.
Quad-color dark-bright pulse trapping in a fiber laser
Authors: Zhang Boqiang , Zeng Chao , Si Ruixue , Hu Jincheng , Luo Ding , Du Yueqing , Mao Dong , Zhao Jianlin
Published: January 2025

Quad-color dark-bright pulse trapping is reported, for the first time to our knowledge, in a fiber laser, where degeneracy and interdependency behaviors are observed. In the temporal domain, the pulses at quad colors are mutually trapped with double M-shape spectra, each of which operates at a dark or bright state, and all of which degenerate spontaneously into one dark-bright pulse pair (DBPP). In the frequency domain, the DBPPs show a switchable mirror-symmetry feature of dark and bright states: bright-dark-dark-bright or dark-bright-bright-dark state, indicating an interesting interdependency between the state and color. Such degeneracy and interdependency behaviors are attributed to the cross-phase modulation (XPM) of the dark and bright pulses at different colors, not only in but also between the bands and also between the orthogonally-polarized components. This work reveals that the DBPPs at different bands can further self-assemble into one DBPP through the XPM, showcasing the evidence and possibility of undiscovered multi-color bright-dark patterns in laser cavities, such as bound state of bright-dark pulses and their complexes.
Quadrant-partitioning uniformly distributed modulation for amplifier-free optical coherent systems
Authors: Zhang Ziheng , Wen Lizhi , Cai Yi , Zhao Jian
Published: January 2025

Amplifier-free coherent systems are promising for short-reach links, but these systems are constrained by signal peak power instead of average power. In this paper, we propose a novel, to the best of our knowledge, quadrant-partitioning uniformly distributed modulation (QP-UDM) scheme for peak-power-constrained amplifier-free systems. The proposed scheme achieves finer modulation orders than conventional UDM schemes. It also avoids the problem in conventional amplitude-division irregular quadrature amplitude modulation, where the order of check bit sequence would be disrupted when there are errors, resulting in the failure of forward error correction decoding. When compared to probabilistic shaping (PS), the proposed QP-UDM has a lower peak-to-average-power ratio. Experiments of a 28 Gbaud amplifier-free system with the modulation order varying from 36 to 104 show that the proposed QP-UDM scheme solves the problem of conventional UDM schemes and outperforms PS-QAM at the same entropy.
Oxygen-binding proteins aid oxygen diffusion to enhance fitness of a yeast model of multicellularity
Authors: Wong Whitney , Bravo Pablo , Yunker Peter J. , Ratcliff William C. , Burnetti Anthony J.
Published: January 2025

Oxygen availability is a key factor in the evolution of multicellularity, as larger and more sophisticated organisms often require mechanisms allowing efficient oxygen delivery to their tissues. One such mechanism is the presence of oxygen-binding proteins, such as globins and hemerythrins, which arose in the ancestor of bilaterian animals. Despite their importance, the precise mechanisms by which oxygen-binding proteins influenced the early stages of multicellular evolution under varying environmental oxygen levels are not yet clear. We address this knowledge gap by heterologously expressing the oxygen-binding proteins myoglobin and myohemerythrin in snowflake yeast, a model system of simple, undifferentiated multicellularity. These proteins increased the depth and rate of oxygen diffusion, increasing the fitness of snowflake yeast growing aerobically. Experiments show that, paradoxically, oxygen-binding proteins confer a greater fitness benefit for larger organisms when O2 is least limiting. We show via biophysical modeling that this is because facilitated diffusion is more efficient when oxygen is abundant, transporting a greater quantity of O2 which can be used for metabolism. By alleviating anatomical diffusion limitations to oxygen consumption, the evolution of oxygen-binding proteins in the oxygen-rich Neoproterozoic may have been a key breakthrough enabling the evolution of increasingly large, complex multicellular metazoan lineages.
ASGCL: Adaptive Sparse Mapping-based graph contrastive learning network for cancer drug response prediction
Authors: Dong Yunyun , Zhang Yuanrong , Qian Yuhua , Zhao Yiming , Yang Ziting , Feng Xiufang
Published: January 2025

Personalized cancer drug treatment is emerging as a frontier issue in modern medical research. Considering the genomic differences among cancer patients, determining the most effective drug treatment plan is a complex and crucial task. In response to these challenges, this study introduces the Adaptive Sparse Graph Contrastive Learning Network (ASGCL), an innovative approach to unraveling latent interactions in the complex context of cancer cell lines and drugs. The core of ASGCL is the GraphMorpher module, an innovative component that enhances the input graph structure via strategic node attribute masking and topological pruning. By contrasting the augmented graph with the original input, the model delineates distinct positive and negative sample sets at both node and graph levels. This dual-level contrastive approach significantly amplifies the model’s discriminatory prowess in identifying nuanced drug responses. Leveraging a synergistic combination of supervised and contrastive loss, ASGCL accomplishes end-to-end learning of feature representations, substantially outperforming existing methodologies. Comprehensive ablation studies underscore the efficacy of each component, corroborating the model’s robustness. Experimental evaluations further illuminate ASGCL’s proficiency in predicting drug responses, offering a potent tool for guiding clinical decision-making in cancer therapy.
A framework for managing infectious diseases in rural areas in low- and middle-income countries in the face of climate change—East Africa as a case study
Authors: Worsley-Tonks Katherine E. L. , Angwenyi Shaleen , Carlson Colin , Cissé Guéladio , Deem Sharon L. , Ferguson Adam W. , Fèvre Eric M. , Kimaro Esther G. , Kimiti David W. , Martins Dino J. , Merbold Lutz , Mottet Anne , Murray Suzan , Muturi Mathew , Potter Teddie M. , Prasad Shailendra , Wild Hannah , Hassell James M.
Published: January 2025

Climate change is having unprecedented impacts on human health, including increasing infectious disease risk. Despite this, health systems across the world are currently not prepared for novel disease scenarios anticipated with climate change. While the need for health systems to develop climate change adaptation strategies has been stressed in the past, there is no clear consensus on how this can be achieved, especially in rural areas in low- and middle-income countries that experience high disease burdens and climate change impacts simultaneously. Here, we highlight the need to put health systems in the context of climate change and demonstrate how this can be achieved by taking into account all aspects of infectious disease risk (i.e., pathogen hazards, and exposure and vulnerability to these pathogen hazards). The framework focuses on rural communities in East Africa since communities in this region experience climate change impacts, present specific vulnerabilities and exposure to climate-related hazards, and have regular exposure to a high burden of infectious diseases. Implementing the outlined approach can help make health systems climate adapted and avoid slowing momentum towards achieving global health grand challenge targets.
Research on technological innovation decision-making considering government subsidies and corporate reputation
Authors: Kang Yu , Huang Zhe
Published: January 2025

Aiming at the information asymmetry between pharmaceutical enterprises’ technological innovation decisions and government subsidy strategy, this paper establishes a differential game model consisting of the government and a single pharmaceutical company, proposes three different government subsidy strategies, and obtains an equilibrium solution with the help of the Hamilton-Jacobi-Bellman equation, taking into consideration of the transmission effect of the enterprise’s reputation. First, the innovation decisions of pharmaceutical firms without government subsidies are analysed, and based on this, the optimal strategies with government subsidies for non-cooperative pacts and cooperation between the government and enterprises are analysed separately. In addition, the effects of different subsidy strategies on the government’s investment efficiency, corporate reputation, and the choice of corporate innovation strategies are compared, and the results are verified by numerical analysis. Finally, based on the results of the study, references and suggestions are provided for the formulation of government subsidy policies as well as corporate innovation decisions. The results show that: government subsidies can effectively stimulate the innovation ability of pharmaceutical enterprises and improve their reputation; the more sensitive an enterprise’s reputation is to the coefficient of technological innovation, the more it can improve the enterprise’s innovation level; and the coordination contract of government-enterprise cooperation can realize the Pareto improvement of the benefits of the government and enterprises.
Semi-field studies on biochemical markers of honey bee workers (Apis mellifera) after exposure to pesticides and their mixtures
Authors: Murawska Agnieszka , Berbeć Ewelina , Latarowski Krzysztof , Roman Adam , Migdał Paweł
Published: January 2025

Due to the fact that many different pesticides are used in crop production and their residues can accumulate in the environment, bees are in contact with various pesticides at the same time. Most studies on their influence on honey bees focus on single substances in concentrations higher than those found in the environment. Our study assessed the chronic effects of commonly used pesticides and their mixtures on selected biochemical markers in worker bee hemolymph. Workers developed in the hive and were provisioned with to pesticides in concentrations corresponding to residues detected in pollen, honey, and/or nectar. Colonies were exposed daily to 0.5L for 7 days by feeding a sugar syrup containing a formulation of acetamiprid (250 ppb) (insecticide), glyphosate (7200 ppb) (herbicide), and tebuconazole (147 ppb) (fungicide) administered alone, in a binary or ternary mixture. Administered alone, acetamiprid significantly decreased the level of urea in the hemolymph of worker honey bees. Glyphosate did not affect significantly the level/activity of any of the biochemical markers. Tebuconazole caused changes in the levels of most of the studied biochemical markers. We found that tebuconazole, which as a fungicide is generally considered safe for bees, may be harmful and more research is required. The impact of fungicides is a crucial element of the assessment of threats to honey bees.
Developing and validating a HEalthCare NAvigation Competency (HECNAC) Scale for refugees in the United States
Authors: Yeo Sarah , Lee Inseok , Ehiri John , Magrath Priscilla , Ernst Kacey , Kim Yu Ri , Alaofè Halimatou
Published: January 2025

The complex healthcare system in the United States (US) poses significant challenges for people, particularly minorities such as refugees. Refugees often encounter additional layers of challenges to healthcare navigation due to unfamiliarity with the system, limited health literacy, and language barriers. Despite their challenges, it is difficult to identify the gaps as few tools exist to measure navigation competency among this population and many conventional tools assume English proficiency, making them inadequate for refugees and other immigrants. To address this gap, this study developed and validated a HEalthCare NAvigation Competency (HECNAC) Scale tailored to refugees’ needs. The scale development process followed three phases: domain identification through a literature review and stakeholder interviews (n = 15), content validation through the Delphi method (2 rounds, n = 12), and face validity assessment via cognitive interviews (2 rounds, n = 4). Based on a literature review and stakeholder interviews, the initial version of the scale was developed, including ten domains and 47 items. An introductory email concerning the scale and the Delphi process was subsequently sent to 21 eligible experts, including staff from refugee resettlement agencies, health care providers serving refugee communities, and refugees. Twelve experts completed the two rounds of the Delphi, resulting in a consensus on 39 items. After conducting cognitive interviews with 4 Afghan refugees, the scale was finalized with ten domains and 35 items. The finalized scale captures multifaceted aspects of healthcare navigation crucial for refugees, organized into domains such as health system knowledge, insurance, making an appointment, transportation, preparing for a visit, in the clinic, interpretation, medicine, medical bills, and preventive care. Overall, the HECNAC Scale represents a significant step towards understanding and assessing refugees’ competencies in navigating the US healthcare system. It has the potential to guide tailored interventions and standardized training curricula and ultimately mitigate persistent barriers faced by refugees in accessing healthcare services.
Fast and accurate imputation of genotypes from noisy low-coverage sequencing data in bi-parental populations
Authors: Triay Cécile , Boizet Alice , Fragoso Christopher , Gkanogiannis Anestis , Rami Jean-François , Lorieux Mathias
Published: January 2025

Motivation

Genotyping of bi-parental populations can be performed with low-coverage next-generation sequencing (LC-NGS). This allows the creation of highly saturated genetic maps at reasonable cost, precisely localized recombination breakpoints (i.e., the crossovers), and minimized mapping intervals for quantitative-trait locus analysis. The main issues with these low-coverage genotyping methods are (1) poor performance at heterozygous loci, (2) high percentage of missing data, (3) local errors due to erroneous mapping of sequencing reads and reference genome mistakes, and (4) global, technical errors inherent to NGS itself. Recent methods like Tassel-FSFHap or LB-Impute are excellent at addressing issues 1 and 2, but nonetheless perform poorly when issues 3 and 4 are persistent in a dataset (i.e., “noisy” data). Here, we present a new algorithm for imputation of LC-NGS data that eliminates the need of complex pre-filtering of noisy data, accurately types heterozygous chromosomal regions, precisely estimates crossover positions, corrects erroneous data, and imputes missing data. The imputation of genotypes and recombination breakpoints is based on maximum-likelihood estimation. We compare its performance with Tassel-FSFHap and LB-Impute using simulated data and two real datasets. NOISYmputer is consistently more efficient than the two other software tested and reaches average breakpoint precision of 99.9% and average recall of 99.6% on illumina simulated dataset. NOISYmputer consistently provides precise map size estimations when applied to real datasets while alternative tools may exhibit errors ranging from 3 to 1845 times the real size of the chromosomes in centimorgans. Furthermore, the algorithm is not only highly effective in terms of precision and recall but is also particularly economical in its use of RAM and computation time, being much faster than Hidden Markov Model methods.

Availability

NOISYmputer and its source code are available as a multiplatform (Linux, macOS, Windows) Java executable at the URL https://gitlab.cirad.fr/noisymputer/noisymputerstandalone/-/tree/1.0.0-RELEASE?reftype=tags.
Aquaporin-2 in the early stages of the adenine-induced chronic kidney disease model
Authors: Oronel Lucas H. , Ortiz Maria , Yarza Carolina , Gayone Sofía , Davio Carlos , Majowicz Mónica , Albertoni Borghese Maria Florencia
Published: January 2025

Chronic kidney disease (CKD) is one of the leading health problems in the world. It is silent in the early stages and gradually progresses, inducing renal physiological and structural alterations. Moreover, CKD is associated with impaired life quality, increased risk for cardiovascular diseases, and reduced life expectancy. Different CKD animal models differ in underlying etiology, time of onset, and associated diseases. The 0.25% adenine diet induces progressive kidney damage, constituting an adequate model mimicking human CKD. Vasopressin (VP) was postulated as a mediator of CKD, mainly acting through its V2 receptors. However, the molecular mechanisms involved in the pathogenesis of this condition and its progression still are not entirely understood. This study aimed to evaluate if AQP2 expression is altered in an adenine-induced model of CKD in rats at early stages of development (two weeks) and to assess a potential beneficial effect of Tolvaptan (a V2 receptor antagonist) treatment. We showed an increased renal medullary AQP2 expression at two weeks of adenine administration. This increase was mainly cytoplasmic, explaining the increased urinary volume of CKD rats and suggesting a possible non-canonical role for AQP2. In addition, Tolvaptan effectively inhibited the V2 receptor in both control and CKD rats, decreasing AQP2 expression and increasing diuresis. Moreover, Tolvaptan slightly reduced BUN and plasma creatinine. On the other hand, the renal alterations induced by adenine in CKD rats were not prevented by Tolvaptan.
Distinguishing classes of neuroactive drugs based on computational physicochemical properties and experimental phenotypic profiling in planarians
Authors: Ireland Danielle , Rabeler Christina , Rao Sagar , Richardson Rudy J. , Collins Eva-Maria S.
Published: January 2025

Mental illnesses put a tremendous burden on afflicted individuals and society. Identification of novel drugs to treat such conditions is intrinsically challenging due to the complexity of neuropsychiatric diseases and the need for a systems-level understanding that goes beyond single molecule-target interactions. Thus far, drug discovery approaches focused on target-based in silico or in vitro high-throughput screening (HTS) have had limited success because they cannot capture pathway interactions or predict how a compound will affect the whole organism. Organismal behavioral testing is needed to fill the gap, but mammalian studies are too time-consuming and cost-prohibitive for the early stages of drug discovery. Behavioral medium-throughput screening (MTS) in small organisms promises to address this need and complement in silico and in vitro HTS to improve the discovery of novel neuroactive compounds. Here, we used cheminformatics and MTS in the freshwater planarian Dugesia japonica–an invertebrate system used for neurotoxicant testing–to evaluate the extent to which complementary insight could be gained from the two data streams. In this pilot study, our goal was to classify 19 neuroactive compounds into their functional categories: antipsychotics, anxiolytics, and antidepressants. Drug classification was performed with the same computational methods, using either physicochemical descriptors or planarian behavioral profiling. As it was not obvious a priori which classification method was most suited to this task, we compared the performance of four classification approaches. We used principal coordinate analysis or uniform manifold approximation and projection, each coupled with linear discriminant analysis, and two types of machine learning models–artificial neural net ensembles and support vector machines. Classification based on physicochemical properties had comparable accuracy to classification based on planarian profiling, especially with the machine learning models that all had accuracies of 90–100%. Planarian behavioral MTS correctly identified drugs with multiple therapeutic uses, thus yielding additional information compared to cheminformatics. Given that planarian behavioral MTS is an inexpensive true 3R (refine, reduce, replace) alternative to vertebrate testing and requires zero a priori knowledge about a chemical, it is a promising experimental system to complement in silico cheminformatics to identify new drug candidates.
Risk of childlessness in help-seeking men with Peyronie’s disease—A Swedish longitudinal study
Authors: Kuja-Halkola Ralf , Henningsohn Lars , Zietsch Brendan , Larsson Henrik , Cederlöf Martin
Published: January 2025

Peyronie’s disease (PD) is a disorder of the penis that is associated with poor mental health, lowered psychosocial- and sexual wellbeing, which may increase the risk of childlessness in men affected by the disorder. Although this is an issue of significant clinical importance, it has not been addressed in research to date. We conducted a longitudinal cohort study based on data from Swedish national registers utilizing a large sample of help-seeking men with PD, along with matched subjects from the general population. We assessed the probability and odds ratio of childlessness, modeled with logistic regressions, and offspring rate ratio, modeled with Poisson regression. We found that the probability of childlessness was somewhat lowered for men with PD aged between 35 and 71 years at end of follow-up. Men with PD aged 35 or less showed slightly elevated probabilities of childlessness. Specifically, odds ratios for childlessness were between 0.5 and 1.0 for men aged above 35, and between 1 and 1.5 for men aged less than 35, although the confidence intervals for increased odds partly included the null. Analyses of men’s rate of offspring showed similar pattern, with higher rate ratios for older men and lower for younger men. Although more research is needed, the findings of this study suggest that clinical urological practice may be enhanced by a proactive discussions about the potential issue of childlessness in younger men with PD.
The impact of intermittent preventive treatment in school aged children with dihydroartemisinin piperaquine and artesunate amodiaquine on IgG response against six blood stage Plasmodium falciparum antigens
Authors: Lyimo Eric , Makenga Geofrey , Turner Louise , Lavstsen Thomas , Lusingu John P. A. , Van geertruyden Jean-Pierre , Minja Daniel T. R. , Wang Christian W. , Baraka Vito
Published: January 2025

Several interventional strategies have been implemented in malaria endemic areas where the burden is high, that include among others, intermittent preventive treatment (IPT), a tactic that blocks transmission and can reduce disease morbidity. However, the implementation IPT strategies raises a genuine concern, intervening the development of naturally acquired immunity to malaria which requires continuous contact with parasite antigens. This study investigated whether dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) IPT in schoolchildren (IPTsc) impairs IgG reactivity to six malaria antigens. An IPTsc trial in north-eastern Tanzania administered three doses of DP or ASAQ at four-monthly intervals and the schoolchildren were followed up. This study compared IgG reactivity against GLURP-R2, MSP1, MSP3, and CIDR domains (CIDRa1.1, CIDRa1.4, and CIDRa1.5) of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1) in intervention and control groups using enzyme linked immunosorbent assay (ELISA) technique. During the study, 369 schoolchildren were available for analysis, 119, 134 and 116 participants in the control, DP and ASAQ groups, respectively. Breadth of malaria antigen recognition increased significantly during and after the intervention phases and did not differ between the study groups (Trend test: DP, z-score = 5.92, p < 0.001, ASAQ, z-score = 6.64, p < 0.001 and control, z-score = 5.85, p < 0.001). There were no differences between the control and ASAQ group in the recognition of any of the tested antigens at all visits. In the DP group, however, during the intervention period IPTsc did not impair antibody against MSP1, MSP3, CIDRa1.1, CIDRa1.4 and CIDRa1.5, but it did impair against GLURP-R2. The current study has shown that effective IPTsc with DP or ASAQ does not interfere with the development of antibodies against malaria antigens of the blood stages, suggesting that the advancement of naturally acquired immunity to malaria is not impeded by IPTsc interventions.
Application of attenuated total reflection–Fourier transform infrared spectroscopy in semi-quantification of blood lipids and characterization of the metabolic syndrome
Authors: Gau Tz-Ping , Wen Jen-Hung , Lu I-Wei , Huang Pei-Yu , Lee Yao-Chang , Lee Wei-Po , Lee Hsiang-Chun
Published: January 2025

Background/Purpose

Dyslipidemia, a hallmark of metabolic syndrome (MetS), contributes to atherosclerotic and cardiometabolic disorders. Due to days-long analysis, current clinical procedures for cardiotoxic blood lipid monitoring are unmet. This study used AI-assisted attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy to identify MetS and precisely quantify multiple blood lipid levels with a blood sample of 0.5 µl and the assaying time is approximately 10 minutes.

Methods

ATR-FTIR spectroscopy with 1738 data points in the spectral range of 4000–650 cm−1 was used to analyze the blood samples. An adaptive synthetic technique was used to establish a prevalence-balanced dataset. LDL-C, HDL-C, TG, VLDL-C, and cholesterol levels were defined as the predicted targets of lipid absorption profiles. Linear regression (LR), gradient boosting regression tree (GBT), and histogram-based gradient boosting regression tree (HGBTR) were used to train the models. Lipid profile value prediction was evaluated using R2 and MAE, whereas MetS prediction was evaluated using area under the ROC curve.

Results

A total of 150 blood samples from 25 individuals without MetS and 25 with MetS yielded 491 spectral measurements. In the regression models, HGBT best predicted the targets of TG, CHOL, HDL-C, LDL-C, and VLDL-C with R2 values of 0.854 (0.12), 0.684 (0.08), 0.758 (0.10), and 0.419 (0.11), respectively. The classification model with the greatest AUC was RF (0.978), followed by HGBT (0.972) and GBT (0.967).

Conclusion

The results of this study revealed that predicting MetS and determining blood lipid levels with high R2 values and limited errors are feasible for monitoring during therapy and intervention.
First-line glaucoma monotherapy medication patterns in Finland during 1995–2019 based on a population-based study
Authors: Purola Petri K. M. , Koskinen Seppo V. P. , Uusitalo Hannu M. T.
Published: January 2025

Background

The long-term patterns in first-line glaucoma medication are not well established. Exploring these in longitudinal and population-based settings would provide information for the healthcare systems to plan glaucoma care accordingly.

Objective

To evaluate patterns in first-line glaucoma monotherapy in Finland during 1995–2019 based on nationwide survey and register data.

Methods

A population-based cohort study with 25 years of total follow-up. The cohort (n = 9288) is a random sample drawn from the nationwide health examination survey FinHealth 2017 which represents the Finnish population aged 30 years or older in 2017. Glaucoma patients were selected from the survey participants based on linked register data that included prescriptions and special reimbursements for glaucoma medication. The patterns, length of use, age at initiation, and persistence of first-line glaucoma drug monotherapies were observed during 1995–2019.

Results

A total of 141 glaucoma patients with glaucoma drug monotherapy as a first-line glaucoma therapy were identified from the sample. The proportion of patients continuing with their first-line monotherapy was 64% after 1 year, 37% after 3 years, and 21% after 5 years of follow-up. During the 25 years there was a shift from beta-blockers to prostaglandin analogues as the prominent first-line glaucoma drug class. The length of use was longer for prostaglandin analogues compared with beta-blockers among patients continuing with their first-line monotherapy after 5 years of follow-up. The non-persistence rate was 38% of all patients during their first-line monotherapy. Timolol fixed-combinations were the most common second-line glaucoma therapy with a share of 39% after 5 years of follow-up.

Conclusions

During the 25-year follow-up a shift from beta-blockers to prostaglandin analogues had occurred and long initial therapies of over 5 years had become more common. However, the decline in the continuation of the initial therapy still occurred early with 1 out of 3 patients continuing after 3 years. This decline together with the consistent problem of non-persistence remain clinical challenges in topical drug therapy of glaucoma.
MicroRNA-221 protects myocardial contractility in myocardial ischemia/reperfusion injury through phospholamban
Authors: Li Hongyu , Qiu Jimiao , Liu Chang , Yu Guobing , Wu Danyu , Chu Yichun , Wang Kai
Published: January 2025

Objective

To investigate the effects and mechanisms of miRNA 221 on myocardial ischemia/reperfusion injury (MIRI) in mice through the regulation of phospholamban (PLB) expression.

Methods

The MIRI mouse model was created and mice were divided into sham, MIRI, MIRI+ 221, and MIRI+ scr groups, with miRNA 221 overexpression induced in the myocardium of MIRI mice by targeted myocardial injection. Quantitative RT-PCR analysis was performed to observe the variation in miRNA 221, PLB, SERCA2, RYR2, NCX1, Cyt C and caspase 3 mRNA levels in myocardium, while Western blot assessed the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), SERCA2, RYR2, NCX1, Cyt C and caspase 3 proteins. Changes in the structural integrity of the mouse heart were identified with HE and MASSON staining, while TUNEL staining was used to evaluate the TUNEL-positive cells of cardiomyocytes. Changes in myocardium calcium concentration were detected with reagent kits and the targeting interaction between miRNA 221 and PLB was evaluated using a luciferase reporter assay.

Results

In the myocardium of MIRI mice, miRNA 221 level was significantly reduced, while the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), and apoptosis-related genes caspase 3, and Cyt C were increased markedly, as well as calcium levels in myocardium. Following the overexpression of miRNA 221 in myocardium, there was a marked alleviation of myocardial injury and cardiomyocyte apoptosis and necrosis, significant enhancement of left ventricular systolic function, and marked decrease in the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), caspase 3 and Cyt C, as well as a significant decrease in total calcium levels in myocardium.

Conclusions

miRNA 221 can alleviate myocardial injury in mouse myocardial ischemia/reperfusion by suppressing the expression of PLB, thus reducing calcium overload in myocardium.