bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient and family experiences of lysosomal storage diseases in Canada: A qualitative interview study
Authors: Awada Nahya , Holcik Martin 
Published: December 2023

AbstractCanadian patients and families affected by rare genetic lysosomal storage diseases (LSDs) suffer from numerous challenges related to disease management, including issues navigating healthcare and social support services, access to orphan drugs, and intensive treatment regimens. These challenges significantly impact people's quality of life, yet they remain obscure and have not been the subject of comprehensive analysis. Thus, we conducted qualitative interviews with Canadian patients and caregivers living with LSDs to advance current understanding of their experiences with rare‐disease (RD) management and health systems navigation to support patient‐focused RD policies and programs and improve the health outcomes of the 2.8 million Canadians affected by RDs. This study employed a qualitative descriptive research design with inductive thematic analysis. The study data were collected using semi‐structured interviews. Thirty Canadian participants were interviewed in person or remotely via video chat to allow for an interactive discussion and the acquisition of rich data related to the insights and perceptions of people with LSDs. Between April and November 2019, 30 participants (16 patients and 14 caregivers) with experiences with nine types of LSDs and living in seven Canadian provinces were interviewed. Five themes were identified using comprehensive thematic analysis. These themes were the complexity of the diagnosis process; navigation of healthcare systems; psychological, social, and financial implications of LSDs; access to social support services; and access to orphan drugs. Our findings reveal that patients' access to appropriate healthcare and social services is subject to significant delays and lacks care coordination. The process of accessing orphan drugs in Canada is extremely complex and convoluted. The study results also illuminate experiences of RD stigma when navigating healthcare and social support systems. Our study offers new insights into the complex nature and extensive needs of Canadians with LSDs that are currently unmet. The management of these complex diseases requires holistic patient care and support beyond having access to orphan drugs. Our findings highlight the importance of bridging existing gaps between health and social care for RD patients. Policymakers should utilize these results when developing the forthcoming national RD strategy.
Olfactory‐Related Adverse Events: An Analysis of the Food and Drug Administration Adverse Events Reporting System
Authors: Minutello Katrina M. , Lofgren Daniel H. , Lenkeit Christopher P. , Emmer Eriel , Santiago Rivera Olga , Hasan Md Sakibur , Downs Asha 
Published: December 2023

AbstractObjectiveOlfactory dysfunction has gained considerable interest with its association to the coronavirus pandemic. Due to the limited literature on olfactory‐related adverse events (ORAE) associated with medications, this study investigated ORAE reported in the Food and Drug Administration Adverse Event Reporting System (FAERS) to identify the most frequent medications associated with these reactions.Study DesignCross‐sectional analysisSettingFAERS database.MethodsThe FAERS database was accessed to obtain ORAEs from 2012 to 2022. Disproportionality analysis was conducted by calculating the proportional reporting ratios (PRR) and reporting odds ratio (ROR) for anosmia, parosmia, hyposmia, and olfactory dysfunction. A PRR > 2 or ROR > 1 was significant. A multivariate logistical model was used to estimate adjusted ROR for gender and country of origin.ResultsOur final study population consisted of 1111 cases with the following symptoms: anosmia (672), parosmia (364), hyposmia (71), and olfactory dysfunction (4). The most significant ROR signal scores were found for secukinumab (3.42; 95% confidence interval, CI [1.9, 4.01]) for anosmia, levofloxacin (8.86; 95% CI [2.83, 9.8]) for hyposmia, and pregabalin (6.88; 95% CI [2.23, 8.01]) for parosmia. No significant PRR signal scores were found for anosmia, but significant signals were found for citalopram hydrobromide (17.25; 95% CI [17.01, 17.49]) in hyposmia, and dimethyl fumarate (3.18; 95% CI [3.09, 3.27]) in parosmia. No valid PRR or ROR values were found for olfactory dysfunction. Multivariate analysis did not reveal statistically significant differences between genders for any symptoms, but individuals from non‐US countries did exhibit statistically significant elevated risk of anosmia (1.3 (95% CI [1.01, 1.68]).ConclusionPharmacovigilance studies provide an opportunity to evaluate the safety profile of medications regarding ORAE, particularly for those commonly prescribed for sinonasal symptoms. Findings from this study may function as a resource for prescribers and patients.
Maximum likelihood estimation of renal transporter ontogeny profiles for pediatric PBPK modeling
Authors: Hunt J. Porter , Dubinsky Samuel , McKnite Autumn M. , Cheung Kit Wun Kathy , van Groen Bianca D. , Giacomini Kathleen M. , de Wildt Saskia N. , Edginton Andrea N. , Watt Kevin M. 
Published: December 2023

AbstractOptimal treatment of infants with many renally cleared drugs must account for maturational differences in renal transporter (RT) activity. Pediatric physiologically‐based pharmacokinetic (PBPK) models may incorporate RT activity, but this requires ontogeny profiles for RT activity in children, especially neonates, to predict drug disposition. Therefore, RT expression measurements from human kidney postmortem cortical tissue samples were normalized to represent a fraction of mature RT activity. Using these data, maximum likelihood estimated the distributions of RT activity across the pediatric age spectrum, including preterm and term neonates. PBPK models of four RT substrates (acyclovir, ciprofloxacin, furosemide, and meropenem) were evaluated with and without ontogeny profiles using average fold error (AFE), absolute average fold error (AAFE), and proportion of observations within the 5–95% prediction interval. Novel maximum likelihood profiles estimated ontogeny distributions for the following RT: OAT1, OAT3, OCT2, P‐gp, URAT1, BCRP, MATE1, MRP2, MRP4, and MATE‐2 K. Profiles for OAT3, P‐gp, and MATE1 improved infant furosemide and neonate meropenem PBPK model AFE from 0.08 to 0.70 and 0.53 to 1.34 and model AAFE from 12.08 to 1.44 and 2.09 to 1.36, respectively, and improved the percent of data within the 5–95% prediction interval from 48% to 98% for neonatal ciprofloxacin simulations, respectively. Even after accounting for other critical population‐specific maturational differences, novel RT ontogeny profiles substantially improved neonatal PBPK model performance, providing validated estimates of maturational differences in RT activity for optimal dosing in children.
Computation of degree‐based topological indices for the complex structure of ruthenium bipyridine
Authors: Abirami S. Jeyamangala , Raj S. Angelin Kavitha , Siddiqui Muhammad Kamran , Zia Tariq Javed 
Published: December 2023

AbstractIn graph theory, a topological index is an important descriptor that helps analyze the physicochemical properties of the structure of chemical compounds through a chemical graph. Degree‐based topological indices have been extensively studied and linked to a variety of chemical properties. This work aims to construct a complex ruthenium‐bipyridine polymer structure involving triphenylamine, which will be useful in the manufacture of organic light‐emitting diodes, solar cells, organic field‐effect transistors, and photorefractive materials, especially as hole transport material. In order to study this novel complex ruthenium bipyridine structure, we employ a reliable mathematical tool called M‐polynomial and NM‐polynomial of the topological index, which displays some physical and chemical properties in numerical form.
Structure and Defect Engineering of V3S4−xSex Quantum Dots Confined in a Nitrogen‐Doped Carbon Framework for High‐Performance Sodium‐Ion Storage
Authors: Liu Baolin , Li Yizhao , Zhang Hongyu , Wang Shiqiang , Song Huijun , Yuan Chun , Yin Xinxin , Lu Zhenjiang , Hu Jindou , Xie Jing , Cao Yali 
Published: December 2023

AbstractConstructing quantum dot‐scale metal sulfides with defects and strongly coupled with carbon is significant for advanced sodium‐ion batteries (SIBs). Herein, Se substituted V3S4 quantum dots with anionic defects confined in nitrogen‐doped carbon matrix (V3S4−xSex/NC) are fabricated. Introducing element Se into V3S4 crystal expands the interlayer distance of V3S4, and triggers anionic defects, which can facilitate Na+ diffusions and act as active sites for Na+ storage. Meanwhile, the quantum dots tightly encapsulated by conductive carbon framework improve the stability and conductivity of the electrode. Theoretical calculations also unveil that the presence of Se enhances the conductivity and Na+ adsorption ability of V3S4−xSex. These properties contribute to the V3S4−xSex/NC with high specific capacity of 447 mAh g−1 at 0.2 A g−1, and prominent rate and cyclic performance with 504 mAh g−1 after 1000 cycles at 10 A g−1. The sodium‐ion hybrid capacitors (SIHCs) with V3S4−xSex/NC anode and activated carbon cathode can achieve high energy/power density (maximum 144 Wh kg−1/5960 W kg−1), capacity retention ratio of 71% after 4000 cycles at 2 A g−1. This work not only synthesizes V3S4−xSex/NC, but also provides a promising opportunity for designing quantum dots and utilizing defects to improve the electrochemical properties.
Resveratrol protects mesangial cells under high glucose by regulating the miR‐1231/IGF1/ERK pathway
Authors: Zhang Ming , Jin Yingli , Guo Xuerui , Shan Wanxin , Zhang Jinlong , Yuan Aoxue , Shi Yan 
Published: December 2023

AbstractDiabetic nephropathy (DN) is one of the complications of diabetes mellitus and the main cause of end‐stage renal disease (ESRD), which is a serious threat to human health. In DN, mesangial cells (MCs) are a critical target cell that perform a variety of key functions, and abnormal proliferation of MCs is a common and prominent pathological change in DN. In recent years, the investigation of Chinese medicine interventions for DN has increased significantly in recent years due to the many potential adverse effects and controversies associated with the treatment of DN with Western medicines. In this study, we evaluated the protective effect of resveratrol (RES), an active ingredient known as a natural antioxidant, on HMCs under high glucose and explored its possible mechanism of action. We found that RES inhibited the proliferation of human mesangial cell (HMC) under high glucose and blocked cell cycle progression. In the high glucose environment, RES upregulated miR‐1231, reduced IGF1 expression, inhibited the activity of the extracellular signal‐regulated kinase (ERK) signaling pathway and reduced levels of the inflammatory factors TNF‐α and IL‐6. In addition, we found that miR‐1231 mimics were synergistically inhibited with RES, whereas miR‐1231 inhibitor attenuated the protective effect of RES on HMCs. Thus, our results suggest that the protective effect of RES on HMCs under high glucose is achieved, at least in part, through modulation of the miR‐1231/IGF1/ERK pathway. The discovery of this potential mechanism may provide a new molecular therapeutic target for the prevention and treatment of DN, and may also bring new ideas for the clinical research in DN.
Walking with giants: The challenges of variant impact assessment in the giant sarcomeric protein titin
Authors: Weston Timir G. R. , Rees Martin , Gautel Mathias , Fraternali Franca 
Published: December 2023

AbstractTitin, the so‐called “third filament” of the sarcomere, represents a difficult challenge for the determination of damaging genetic variants. A single titin molecule extends across half the length of a sarcomere in striated muscle, fulfilling a variety of vital structural and signaling roles, and has been linked to an equally varied range of myopathies, resulting in a significant burden on individuals and healthcare systems alike. While the consequences of truncating variants of titin are well‐documented, the ramifications of the missense variants prevalent in the general population are less so. We here present a compendium of titin missense variants—those that result in a single amino‐acid substitution in coding regions—reported to be pathogenic and discuss these in light of the nature of titin and the variant position within the sarcomere and their domain, the structural, pathological, and biophysical characteristics that define them, and the methods used for characterization. Finally, we discuss the current knowledge and integration of the multiple fields that have contributed to our understanding of titin‐related pathology and offer suggestions as to how these concurrent methodologies may aid the further development in our understanding of titin and hopefully extend to other, less well‐studied giant proteins.This article is categorized under:
Cardiovascular Diseases > Genetics/Genomics/Epigenetics
Congenital Diseases > Genetics/Genomics/Epigenetics
Congenital Diseases > Molecular and Cellular Physiology
Design Elements of a Platform-Based Ecosystem for Industry Applications
Authors: Millan Michael , Becker Annika , Christou Ester , Flaig Roman , Gorißen Leon , Hinke Christian , Koren István , Lohrmann Vincent , Lüttgens Dirk , Mertens Matthias , Wiesch Marian , Jarke Matthias , Piller Frank T. 
Published: December 2023

AbstractMany companies in the Industry 4.0 (I4.0) environment are still lacking knowledge and experience of how to enter and participate in a platform-based ecosystem to gain long-term competitive advantages. This leads to uncertainty among firms when transforming into platform-based ecosystems. The article presents a structuralist approach to conceptualize the platform-based ecosystem construct, giving an overview of the literature landscape in a model bundled with unified terminology and different perspectives. The holistic process model aggregates the findings of 130 papers regarding platform-based ecosystem literature. It consists of 4 phases and 16 design elements that unify different terminologies from various research disciplines in one framework and provide a structured and process-oriented approach. Besides, use cases for different design elements were developed to make the model apply in an I4.0 context. Use Case I is a methodology that can be used to model and validate usage hypotheses based on usage data to derive optimization potential from identified deviations from real product usage. By collecting and refining data for analyzing different manufacturing applications and machine tool behavior the importance of specific data is shown in Use Case II and it is highlighted which data can be shared from an external perspective. Use Case III deals with strategic modeling of platform-based ecosystems and the research identifies control points that platform players can actively set to adjust their business models within alliance-driven cooperation to create and capture value jointly. Use Case IV investigates the status quo and expectations regarding platform-based ecosystems in the field of laser technology with the help of structured expert interviews. Overall, this chapter presents a framework on industrial platform-based ecosystems that gives researchers and practitioners a tool and specific examples to get started in this emerging topic.
Introduction: Transformations of European Welfare States and Social Rights
Authors: Nielsen Stine Piilgaard Porner , Hammerslev Ole 
Published: December 2023

AbstractIn this introductory chapter, we outline the literature in which the anthology is positioned and the anthology’s contribution hereto. We account for the questions addressed in the anthology and its structure based on three sections that each analyses transformations of European welfare states and social rights from macro, meso and micro level perspectives, respectively. As described in the chapter and illustrated throughout the anthology, the three levels are interlinked: Macro level welfare state transformations influence the meso level of public encounters between welfare professionals and citizens, and on micro level, these encounters have real effect for, for example, citizens’ access to social rights. Linking the levels, the anthology contributes with analytical insights into welfare state transformations and social rights.
Macroinvertebrate communities reveal regional asymmetries in riverine ecosystems along a gradient of water availability in hydrologically distinct years
Authors: Santos Joana Isabel , Silva Carlos , Gonçalves Fernando J. M. , Pereira Joana Luísa , Castro Bruno Branco 
Published: December 2023

AbstractClimate change has been increasing the frequency and severity of drought periods. There is a need to understand how this water scarcity affects aquatic communities. The main aim of this work was to compare the macroinvertebrate communities and their bioindicator value (ecological status sensu the Water Framework Directive) in three Regions [northeast (N), central (C) and south (S)] of Portugal along a water availability and climate gradient, in two consecutive years that reflect hydrologically distinct scenarios (2018 versus 2019). The period prior to sampling (summer and autumn 2017) was extremely dry and hot, whereas climatic fluctuations in 2018–2019 (when the sampling occurred) were closer to the norm. A total of 28 sampling sites were surveyed in streams of Regions where water scarcity is differentially constitutive. The results showed a consistent environmental and ecological gradient in both years, despite the background differences. A coinciding mineralization, temperature, riparian cover and water availability gradient clearly separated Regions C (wettest) and S (driest), with Region N occupying an intermediate position. Region C had overall higher ecological quality (prevalence of sensitive organisms) in both years. Despite our a priori expectations that 2018 would represent a much more stressful condition, with larger differences across Regions (because of their constitutive background), the data suggest that macroinvertebrate communities may be resilient or adapted, to some degree, to hydrological fluctuations. Signs of more favourable conditions in 2019 were also observed (general improvement in ecological status). Studies across hydrological and climatic gradients (in time and space) are particularly important where water availability is becoming more challenging.
Silencing HE4 alleviates the renal fibrosis in lupus nephritis mice by regulating the C3/MMPs/prss axis
Authors: Li Yixia , Zhong Xiaorong , Yang Feng 
Published: December 2023

AbstractTo explore the regulatory effect of human epididymis protein 4 (HE4) on renal fibrosis in mice with lupus nephritis (LN) and the underlying mechanism. Ten-week old MRL/LPR mice were injected with HE4 shRNA adenovirus vector through the renal pelvis for 5 days. Renal tissues were extracted for HE and Masson staining to evaluate pathological changes and fibrosis in lupus nephritis mice. The level of urine protein was measured using a biochemical analyzer, while the expression level of HE4 and p-NF-κB p65 in renal tissues was visualized using an immunofluorescence assay. The level of β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (Kim-1) was determined by the immunohistochemical assay. Western blotting was used to determine the levels of C3, HE4, matrix metalloproteinase-2 (MMP2), MMP9, p-p65, prss23, and prss35 in renal tissues. Compared to wild-type C57BL/6 mice, MRL/LPR mice showed a marked increase in the number of glomeruli, hyperplasic basement membrane, severe infiltration of inflammatory cells in renal tubules and glomeruli, obvious necrosis in glomeruli, elevated fibrosis levels, and increased levels of urine protein, β2-MG, NGAL, Kim-1, C3, HE4, MMP2, MMP9, and p-p65; and decreased levels of prss23 and prss35 were observed in MRL/LPR mice. After the administration of the HE4 shRNA adenovirus vector, the repaired structure of renal tubules and glomeruli improved infiltration of inflammatory cells, reduced collagen fiber and urine protein, suppressed levels of C3, HE4, MMP2, MMP9, and p-P65, and facilitated the expression of prss23 and prss35 which were observed. Silencing HE4 improved renal fibrosis and inhibited inflammation in mice with lupus nephritis, which may play a role in inhibiting C3/MMPs and promoting prss-related protein expression.
Dune Blowouts as Microbial Hotspots and the Changes of Overall Microbial Activity and Photosynthetic Biomass Along with Succession of Biological Soil Crusts
Authors: Chowaniec Karolina , Styburski Jakub , Kozioł Szymon , Pisańska Zofia , Skubała Kaja 
Published: December 2023

AbstractBiological soil crust (BSC) constitutes a consortium of cyanobacteria, algae, lichen, mosses, and heterotrophic microorganisms, forming a miniature ecosystem within the uppermost soil layer. The biomass of different organisms forming BSC and their activity changes along with succession. Previous studies focused primarily on BSC in hyper-arid/arid regions, whereas the ecophysiology of BSC in temperate climates is still not well recognized. In order to determine changes in overall microbial activity and photosynthetic biomass in BSC at different stages of the succession of inland sandy grasslands, we analyzed dehydrogenase activity and determined the content of photosynthetic pigments. We also compared these parameters between BSC developed on the dune ridges and aeolian blowouts in the initial stage of succession. Our study revealed a significant increase in both photosynthetic biomass and overall microbial activity in BSC as the succession of inland shifting sands progresses. We found that chl a concentration in BSC could be considered a useful quantitative indicator of both the presence of photoautotrophs and the degree of soil crust development in warm-summer humid continental climates. The photosynthetic biomass was closely related to increased microbial activity in BSC, which suggests that photoautotrophs constitute a major BSC component. Dune blowouts constitute environmental niches facilitating the development of BSC, compared to dune ridges. High biomass of microorganisms in the dune blowouts may be associated with a high amount of organic material and more favorable moisture conditions. We conclude that deflation fields are key places for keeping a mosaic of habitats in the area of shifting sands and can be a reservoir of microorganisms supporting further settlement of dune slopes by BSC.