bluuebunny/crossref_metadata_2025 huggingface dataset:
Talc
Authors: Ierardi A. Michael , Burns Amanda M. , Bernstein David M.
Published: December 2023

Talc (Mg3Si4O10(OH)2), a hydrated magnesium silicate, consists of magnesium (Mg), silicon and oxygen (SiO2, silica), and water. Inhalation of talc – in particular, cosmetic‐grade talc – has been implicated as a causal agent of mesothelioma among consumers due to the potential presence of trace levels of asbestos. Over the past several decades, the scientific community has taken several steps to evaluate this hypothesis from a human health risk assessment perspective. This chapter presents a summary of the available animal toxicology, epidemiology, and exposure data related to this topic. The focus of this chapter is primarily on cosmetic‐grade talc, as the relatively pure talc used in cosmetic applications provides the best source of data for evaluating the health effects of the mineral itself. The current weight of evidence suggests that relatively pure talc, which is used in cosmetics, as well as other consumer products, does not pose a carcinogenic health risk upon inhalation.
Splenic hemangioendothelial neoplasm in a captive Northern Snakehead from the Potomac River
Authors: Walsh Heather L. , Blazer Vicki S. , Wolf Jeffrey C. , Densmore Christine L.
Published: December 2023

Objective

At the U.S. Geological Survey Leetown Research Laboratory in Kearneysville, West Virginia, an approximately 3-year-old, captive-held Northern Snakehead Channa argus with clinical signs of abdominal distention died and was necropsied 1 day after an examination under anesthesia. A mass discovered in the midcoelomic cavity, presumed to be deformed spleen, was comprised of large, pseudocystic structures that contained considerable volumes of opaque, straw-colored fluid.

Methods

A histopathological evaluation revealed that the tissue consisted of foci of small capillaries, nodular areas of proliferating, pleomorphic endothelial cells, and areas of necrosis within the pseudocyst wall. Positive nuclear and nonspecific immunolabeling with a vascular marker, cluster of differentiation 31, was concentrated in and around vascular spaces.

Result

Based on these observations, the tumor has been putatively identified as a hemangioendothelial neoplasm.

Conclusion

This would represent the first report of a vascular tumor in a Northern Snakehead and, globally, one of the few described neoplasms identified in a member of the Channidae family.
Association between structural brain MRI abnormalities and epilepsy in older adults
Authors: Gugger James J. , Walter Alexa E. , Diaz‐Arrastia Ramon , Huang Juebin , Jack Clifford R. , Reid Robert , Kucharska‐Newton Anna M. , Gottesman Rebecca F. , Schneider Andrea L. C. , Johnson Emily L.
Published: December 2023

Objective

To determine the association between brain MRI abnormalities and incident epilepsy in older adults.

Methods

Men and women (ages 45–64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late‐onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI. We evaluated the relative pattern of cortical thickness, subcortical volume, and white matter integrity among participants with incident LOE after MRI in comparison with participants without seizures. We examined the association between MRI abnormalities and incident LOE using Cox proportional hazards regression. Models were adjusted for demographics, hypertension, diabetes, smoking, stroke, and dementia status.

Results

Among 1251 participants with brain MRI data, 27 (2.2%) developed LOE after MRI over a median of 6.4 years (25–75 percentile 5.8–6.9) of follow‐up. Participants with incident LOE after MRI had higher levels of cortical thinning and white matter microstructural abnormalities before seizure onset compared to those without seizures. In longitudinal analyses, greater number of abnormalities was associated with incident LOE after controlling for demographic factors, risk factors for cardiovascular disease, stroke, and dementia (gray matter: hazard ratio [HR]: 2.3, 95% confidence interval [CI]: 1.0–4.9; white matter diffusivity: HR: 3.0, 95% CI: 1.2–7.3).

Interpretation

This study demonstrates considerable gray and white matter pathology among individuals with LOE, which is present prior to the onset of seizures and provides important insights into the role of neurodegeneration, both of gray and white matter, and the risk of LOE.
Development of a Machine Learning Model to Predict the Use of Surgery in Patients With Rheumatoid Arthritis
Authors: Baxter Natalie B. , Lin Ching‐Heng , Wallace Beth I. , Chen Jung‐Sheng , Kuo Chang‐Fu , Chung Kevin C.
Published: December 2023

Objective

One in five patients with rheumatoid arthritis (RA) rely on surgery to restore joint function. However, variable response to disease‐modifying antirheumatic drugs (DMARDs) complicates surgical planning, and it is difficult to predict which patients may ultimately require surgery. We used machine learning to develop predictive models for the likelihood of undergoing an operation related to RA and which type of operation patients who require surgery undergo.

Methods

We used electronic health record data to train two extreme gradient boosting machine learning models. The first model predicted patients’ probabilities of undergoing surgery ≥5 years after their initial clinic visit. The second model predicted whether patients who underwent surgery would undergo a major joint replacement versus a less intensive procedure. Predictors included demographics, comorbidities, and medication data. The primary outcome was model discrimination, measured by area under the receiver operating characteristic curve (AUC).

Results

We identified 5,481 patients, of whom 278 (5.1%) underwent surgery. There was no significant difference in the frequency of DMARD or steroid prescriptions between patients who did and did not have surgery, though nonsteroidal anti‐inflammatory drug prescriptions were more common among patients who did have surgery (P = 0.03). The model predicting use of surgery had an AUC of 0.90 ± 0.02. The model predicting type of surgery had an AUC of 0.58 ± 0.10.

Conclusions

Predictive models using clinical data have the potential to facilitate identification of patients who may undergo rheumatoid‐related surgery, but not what type of procedure they will need. Integrating similar models into practice has the potential to improve surgical planning.
Fuzzy adaptive time‐varying formation control of USVs with actuator faults
Authors: Feng Kelin , Li Kewen , Li Yongming
Published: December 2023

This paper investigates the fuzzy adaptive time‐varying formation control problem for fully‐actuated unmanned surface vehicles (USVs) systems. The studied USVs systems include uncertain dynamics and actuator faults. Fuzzy logic systems (FLSs) and disturbance observer are employed to estimate uncertain nonlinear dynamics in system model and external time‐varying disturbances, respectively. Meanwhile, the prescribed performance control (PPC) technique is applied to construct the constraint requirements of collision avoidance and connectivity preservation in time‐varying formation control. Additionally, a new robust adaptive fault‐tolerant control (FTC) algorithm is presented. Hence, by the aid of adaptive backstepping technique with performance functions, a robust fuzzy adaptive time‐varying formation FTC scheme of time‐varying formation is developed. The proposed formation control scheme not only has the advantages of avoiding collision and preserving connectivity, but also ensures all the signals are uniformly ultimately bounded (UUB). Finally, the simulation results are provided to demonstrate the effectiveness of the proposed approach.
Combinatorial Design of Novel Multiprincipal Element Alloys Using Experimental Techniques
Authors: Gubicza Jenő
Published: December 2023

Multiprincipal element alloys (MPEAs) including high‐entropy alloys are in the focus of materials science since many MPEA compositions exhibit outstanding mechanical and physical properties. These alloys contain 3–6 constituents with similar fractions; therefore, MPEAs correspond to the unexplored middle part of the phase diagrams. The phase composition and the performance of MPEAs are strongly influenced by their chemistry. Thus, it is very important to reveal the correlation between the composition, the structure, and the properties of MPEAs. On the other hand, this task is challenging due to the vast composition space of these alloys. The processing and characterization of combinatorial specimens can yield a fast mapping of compositional libraries of MPEAs. Herein, the experimental techniques developed for manufacturing and investigation of these alloys are overviewed and the results are critically discussed. Finally, further development directions in the field of combinatorial MPEAs are recommended in order to improve the study of the different alloy compositions.
Photo‐Triggered Cascade Therapy: A NIR‐II AIE Luminogen Collaborating with Nitric Oxide Facilitates Efficient Collagen Depletion for Boosting Pancreatic Cancer Phototheranostics
Authors: Li Dan , Chen Xiaohui , Dai Wenbin , Jin Qiao , Wang Dong , Ji Jian , Tang Ben Zhong
Published: December 2023

The dense extracellular matrix (ECM) in the pancreatic cancer severely hampers the penetration of nanodrugs, which causes inferior therapeutic efficacy. To address this issue, a multifunctional liposome, namely, Lip‐DTI/NO, integrating a type‐I photosensitizer DTITBT with glutathione (GSH) or heat‐responsive nitric oxide (NO) donor S‐nitroso‐N‐acetyl‐D‐penicillamine (SNAP) is constructed to deplete the tumor ECM, leading to enhanced drug delivery and consequently improved phototherapy. The loaded DTITBT possesses multiple functions including NIR‐II fluorescence imaging, efficient superoxide radical (O2•−) generation and excellent photothermal conversion efficiency, making it feasible for precisely pinpointing the tumor in the phototherapy process. Responding to the intracellular overexpressed glutathione or heat produced by photothermal effect of DTITBT, NO can be released from SNAP. Upon 808 nm laser irradiation, Lip‐DTI/NO could selectively induce in situ generation of peroxynitrite anion (ONOO−) in tumor after cascade processes including O2•− production, GSH or heat‐triggered NO release, and rapid reaction between O2•− and NO. The generated ONOO− could activate the expression of endogenous matrix metalloproteinases which could efficiently digest collagen of tumor ECM, thus facilitating enhanced penetration and accumulation of Lip‐DTI/NO in tumor. In vivo evaluation demonstrates the notable therapeutic efficacy via ONOO−‐potentiated synergistic photodynamic‐photothermal therapies on both subcutaneous and orthotopic pancreatic cancer model.
Plasmonic Nanocone Scanning Antenna: Fabrication and Optical Properties
Authors: Kambalathmana Haritha , Flatae Assegid Mengistu , Biagini Claudio , Tantussi Francesco , De Angelis Francesco , Agio Mario
Published: December 2023

Optical antennas are nanostructures that introduce unprecedented possibilities for light–matter interaction at the nanoscale. An appropriately tailored plasmonic antenna can enhance the total radiative decay rate and modify the angular radiation pattern of a single‐quantum emitter through controlled near‐field coupling. Despite their ability to surpass the fundamental diffraction limit and confine the electromagnetic field to a tiny mode volume, fabricating 3D sharp scanning nanoscale plasmonic structures with desired aspect ratio is yet an ambitious goal. The fabrication of nanocones by gold evaporation on commercial atomic force microscopy probes followed by a focused ion beam milling technique is presented. The method is versatile and allows the fabrication of nanocones with desired dimensions around 100 nm along with an aspect ratio of ≈1. Their optical properties are studied and it is shown how the variation in the refractive index of the dielectric substrate affects the localized surface plasmon resonance of the nanocones, the decay rate enhancement, and the quantum yield of an emitter relevant for fluorescence/Raman scanning experiments. Theoretical studies using finite‐difference time‐domain calculations have guided the fabrication process and are consistent with experimental results.
Do regional trade agreements affect agri‐food trade? Evidence from a meta‐analysis
Authors: Afesorgbor Sylvanus Kwaku , Fiankor Dela‐Dem Doe , Demena Binyam Afewerk
Published: December 2023

Regional trade agreements (RTAs) have experienced significant growth worldwide, leading to an increase in studies assessing their impact on bilateral trade flows. With the availability of disaggregated trade data, numerous studies have examined the influence of these agreements specifically on agri‐food trade. However, the results of these studies exhibit heterogeneity, posing challenges for policymakers seeking to understand the effects of RTAs on agri‐food trade. To address this issue, we conducted a meta‐analysis of 61 studies investigating the effects of various RTAs on agri‐food trade. Using funnel asymmetric testing, our analysis reveals the presence of publication bias in the existing literature. By accounting for this bias, we found robust evidence that RTAs positively and significantly promote agri‐food trade. Notably, the extent of this effect depends on the depth of economic integration within the RTA, distinguishing between customs unions and free trade agreements, as well as the classification of agri‐food products as primary or processed. The ex‐post effects of RTAs on agri‐food trade are less pronounced when we control for both publication bias and heterogeneity, compared to controlling only for publication bias.
Degradable Block Copolymer Nanoparticles Synthesized by Polymerization‐Induced Self‐Assembly
Authors: Zhang Shudi , Li Ruoyu , An Zesheng
Published: December 2023

Polymerization‐induced self‐assembly (PISA) combines polymerization and in situ self‐assembly of block copolymers in one system and has become a widely used method to prepare block copolymer nanoparticles at high concentrations. The persistence of polymers in the environment poses a huge threat to the ecosystem and represents a significant waste of resources. There is an urgent need to develop novel chemical approaches to synthesize degradable polymers. To meet with this demand, it is crucial to install degradability into PISA nanoparticles. Most recently, degradable PISA nanoparticles have been synthesized by introducing degradation mechanisms into either shell‐forming or core‐forming blocks. This Minireview summarizes the development in degradable block copolymer nanoparticles synthesized by PISA, including shell‐degradable, core‐degradable, and all‐degradable nanoparticles. Future development will benefit from expansion of polymerization techniques with new degradation mechanisms and adaptation of high‐throughput approaches for both PISA syntheses and degradation studies.
Integration of miRNA in exosomes and single‐cell RNA‐seq profiles in endemic osteoarthritis, Kashin–Beck disease
Authors: Wang Xi , Zhang Yu , Wu Yifan , Wang Chaowei , Li Shujin , Yuan Yuequan , Lv Xi , Liu Yanli , Chen Feihong , Chen Sijie , Zhang Feiyu , Guo Xiong , Ning Yujie , Zhao Hongmou
Published: December 2023

Kashin–Beck disease (KBD) is an endemic, chronic degenerative joint disease in China. Exosomes miRNAs, as signaling molecules in intercellular communication, can transfer specific biological martials into target cell to regulate their function and might participate in the pathogenesis of KBD. We isolated serum and chondrocytes‐derived exosomes, miRNA sequencing revealed exosomes miRNA profiles and differentially expressed miRNAs (DE‐miRNAs) were identified. The target genes were predicted of known and novel DE‐miRNAs with TargetScan 5.0 and miRanda 3.3a database. Single‐cell RNA sequencing (scRNA‐seq) was performed to identify chondrocyte clusters and their gene signatures in KBD. And we performed comparative analysis between the serum and chondrocytes‐derived exosomes DE‐miRNA target genes and differentially expressed genes of each cell clusters. A total of 20 DE‐miRNAs were identified in serum‐derived exosomes. In the miRNA expression of chondrocytes‐derived exosomes, 53 DE‐miRNAs were identified. 16,063 predicted targets were identified as the target genes in the serum‐derived exosomes, 57,316 predicted targets were identified as the target genes in the chondrocytes‐derived exosomes. Seven clusters were labeled by cell type according to the expression of previously described markers. Three hundred fifteen common genes were found among serum/chondrocytes‐derived exosomes DE‐miRNA target genes and DEGs identified by scRNA‐seq analysis. We firstly integratly analyzed the serum and chondrocytes exosomes miRNA with single‐cell RNA sequencing (scRNA‐seq) data of KBD chondrocyte, the results showed that DE‐miRNAs in exosomes might play a potential role in regulating genes expression in different KBD chondrocytes clusters by exosomes mediating cell–cell communications functions, which could improve the new diagnosis and treatment methods for KBD.
A systematic review of the factors affecting girls' participation in science, technology, engineering, and mathematics subjects
Authors: Msambwa Msafiri M. , Daniel Kangwa , Lianyu Cai , Fute Antony
Published: December 2023

There have been global efforts to achieve the sustainable development goals (SDGs) on quality education, gender equality, industry, innovation, and infrastructure development; however, in science, technology, engineering, and mathematics (STEM), men still dominate these fields at the highest levels, as boys dominate STEM subjects in schools. Thus, there is a need to improve female participation in these fields at all levels. Therefore, this systematic review examined the empirical evidence on the factors affecting girls' participation in STEM subjects. We conducted a comprehensive literature search using electronic databases such as Web of Science, Scopus, EBSCO‐host, and Google Scholar. An analysis of 165 scholarly publications was done using a systematic methodology. The study found that only 10% of the studies indicated that girls' poor participation in STEM could be attributed to personal factors and 61% to environmental factors. Additionally, behavioral factors accounted for 29% of the sampled studies, which found that negative attitudes, lack of career plans, lack of collaboration, interest, poor self‐concept, self‐efficacy, and low motivation were identified as factors that affect girls' participation in STEM subjects. The findings highlight a comprehensive overview of the current knowledge of girls in STEM, providing policymakers, educators, and practitioners with valuable insights into creating an enabling environment that supports more girls in STEM subjects. Furthermore, it contributes to the global efforts to achieve the SDGs 4, 5, and 9.
Renal Epithelial Mitochondria: Implications for Hypertensive Kidney Disease
Authors: Stadler Krisztian , Ilatovskaya Daria V.
Published: December 2023

According to the Centers for Disease Control and Prevention, 1 in 2 U.S. adults have hypertension, and more than 1 in 7 chronic kidney disease. In fact, hypertension is the second leading cause of kidney failure in the United States; it is a complex disease characterized by, leading to, and caused by renal dysfunction. It is well‐established that hypertensive renal damage is accompanied by mitochondrial damage and oxidative stress, which are differentially regulated and manifested along the nephron due to the diverse structure and functions of renal cells. This article provides a summary of the relevant knowledge of mitochondrial bioenergetics and metabolism, focuses on renal mitochondrial function, and discusses the evidence that has been accumulated regarding the role of epithelial mitochondrial bioenergetics in the development of renal tissue dysfunction in hypertension. © 2024 American Physiological Society.
Compr Physiol
14:5225‐5242, 2024.
Advanced Imaging Techniques for the Characterization of Subcellular Organelle Structure in Pancreatic Islet β Cells
Authors: McLaughlin Madeline R. , Weaver Staci A. , Syed Farooq , Evans‐Molina Carmella
Published: December 2023

Type 2 diabetes (T2D) affects more than 32.3 million individuals in the United States, creating an economic burden of nearly $966 billion in 2021. T2D results from a combination of insulin resistance and inadequate insulin secretion from the pancreatic β cell. However, genetic and physiologic data indicate that defects in β cell function are the chief determinant of whether an individual with insulin resistance will progress to a diagnosis of T2D. The subcellular organelles of the insulin secretory pathway, including the endoplasmic reticulum, Golgi apparatus, and secretory granules, play a critical role in maintaining the heavy biosynthetic burden of insulin production, processing, and secretion. In addition, the mitochondria enable the process of insulin release by integrating the metabolism of nutrients into energy output. Advanced imaging techniques are needed to determine how changes in the structure and composition of these organelles contribute to the loss of insulin secretory capacity in the β cell during T2D. Several microscopy techniques, including electron microscopy, fluorescence microscopy, and soft X‐ray tomography, have been utilized to investigate the structure‐function relationship within the β cell. In this overview article, we will detail the methodology, strengths, and weaknesses of each approach. © 2024 American Physiological Society.
Compr Physiol
14:5243‐5267, 2024.
Pathophysiology of Red Blood Cell Trapping in Ischemic Acute Kidney Injury
Authors: McLarnon Sarah R.
Published: December 2023

Red blood cell (RBC) trapping describes the accumulation of RBCs in the microvasculature of the kidney outer medulla that occurs following ischemic acute kidney injury (AKI). Despite its prominence in human kidneys following AKI, as well as evidence from experimental models demonstrating that the severity of RBC trapping is directly correlated with renal recovery, to date, RBC trapping has not been a primary focus in understanding the pathogenesis of ischemic kidney injury. New evidence from rodent models suggests that RBC trapping is responsible for much of the tubular injury occurring in the initial hours after kidney reperfusion from ischemia. This early injury appears to result from RBC cytotoxicity and closely reflects the injury profile observed in human kidneys, including sloughing of the medullary tubules and the formation of heme casts in the distal tubules. In this review, we discuss what is currently known about RBC trapping. We conclude that RBC trapping is likely avoidable. The primary causes of RBC trapping are thought to include rheologic alterations, blood coagulation, tubular cell swelling, and increased vascular permeability; however, new data indicate that a mismatch in blood flow between the cortex and medulla where medullary perfusion is maintained during cortical ischemia is also likely critical. The mechanism(s) by which RBC trapping contributes to renal functional decline require more investigation. We propose a renewed focus on the mechanisms mediating RBC trapping, and RBC trapping‐associated injury is likely to provide important knowledge for improving AKI outcomes. © 2024 American Physiological Society.
Compr Physiol
14:5325‐5343, 2024.
Common caregiver illness representations in the context of family‐based treatment: Commentary on Marchetti and Sawrikar (2023)
Authors: Van Huysse Jessica L. , Bilek Emily L.
Published: December 2023

In their systematic review on parent illness representations in their children with anorexia nervosa (AN), Marchetti and Sawrikar (International Journal of Eating Disorders, 2023) integrate past research on the parental experience of the illness, investigating whether the Common Sense Model of Self‐Regulation (CSM) is a useful framework for understanding parental responses to AN. Given that family‐based treatment (FBT) is a first‐line treatment for adolescents with eating disorders and is based upon integrating parents into the treatment process, it is especially relevant to explore how parent illness representations may impact FBT. In this commentary, we describe how FBT is designed to support parents and address many of the common unhelpful beliefs and emotions associated with parenting an adolescent with AN. We include specific examples of how parents can be supported within FBT as manualized. We also examine parental representations that may not be addressed by FBT, and how these may impact treatment outcomes in FBT, possibly via the impact of expressed emotion. Future research is needed to determine if modifications to FBT are required to address parental representations of the illness. We end by expanding upon Marchetti and Sawrikar's suggestions on how treatment could be extended to better support parents as necessary.
Scaled ILU smoothers for Navier–Stokes pressure projection
Authors: Thomas Stephen , Carr Arielle , Mullowney Paul , Świrydowicz Katarzyna , Day Marcus
Published: December 2023

Incomplete LU (ILU) smoothers are effective in the algebraic multigrid (AMG) ‐cycle for reducing high‐frequency components of the error. However, the requisite direct triangular solves are comparatively slow on GPUs. Previous work has demonstrated the advantages of Jacobi iteration as an alternative to direct solution of these systems. Depending on the threshold and fill‐level parameters chosen, the factors can be highly nonnormal and Jacobi is unlikely to converge in a low number of iterations. We demonstrate that row scaling can reduce the departure from normality, allowing us to replace the inherently sequential solve with a rapidly converging Richardson iteration. There are several advantages beyond the lower compute time. Scaling is performed locally for a diagonal block of the global matrix because it is applied directly to the factor. Further, an ILUT Schur complement smoother maintains a constant GMRES iteration count as the number of MPI ranks increases, and thus parallel strong‐scaling is improved. Our algorithms have been incorporated into hypre, and we demonstrate improved time to solution for linear systems arising in the Nalu‐Wind and PeleLM pressure solvers. For large problem sizes, GMRESAMG executes at least five times faster when using iterative triangular solves compared with direct solves on massively parallel GPUs.
The role of stakeholder structure in fostering community ownership: A case study of community‐based projects
Authors: Kobashi Yurie , Goto Aya , Chi Chunhuei
Published: December 2023

Community health projects have played a crucial role in improving health issues. Listening to communities' voices and achieving community ownership are essential for conducting effective health projects. However, there are limited studies on the frameworks for collecting, aggregating, and operationalizing community preferences and values. In this study, we selected two cases of community field surveys from Japan and Cambodia to discuss who may represent a community and propose a practical approach to achieving community ownership. Both cases involved various stakeholders. From the insights of these two cases, we suggested the following three key components in the community project: the community representative, the communicator, and the institute outside the community. Notably, the community representative's role as the community's direct voice should be properly recognized and institutionalised to establish community ownership. We proposed the following key terms of the qualifications of community representatives: they should be able to represent voices from the community, should have extensive experience to decide the project direction and manage the project, and should be independent of outside actors. Our theoretical model of the structure of different stakeholder groups in community‐based projects will be helpful to accelerate community capacity strengthening; moreover, it can help build the appropriate community institution and process, including multi‐stakeholder groups to promote community ownership in health programs.
Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review
Authors: Nag Sagnik , Mitra Oishi , Tripathi Garima , Samanta Souvik , Bhattacharya Bikramjit , Chandane Priti , Mohanto Sourav , Sundararajan Vino , Malik Sumira , Rustagi Sarvesh , Adhikari Suraj , Mohanty Aroop , León‐Figueroa Darwin A. , Rodriguez‐Morales Alfonso J. , Barboza Joshuan J. , Sah Ranjit
Published: December 2023

Background

Autoimmune diseases (AD) are severe pathophysiological ailments that are stimulated by an exaggerated immunogenic response towards self‐antigens, which can cause systemic or site‐specific organ damage. An array of complex genetic and epigenetic facets majorly contributes to the progression of AD, thus providing significant insight into the regulatory mechanism of microRNA (miRNA). miRNAs are short, non‐coding RNAs that have been identified as essential contributors to the post‐transcriptional regulation of host genome expression and as crucial regulators of a myriad of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development.

Aims

This article tends to deliberate and conceptualize the brief pathogenesis and pertinent epigenetic regulatory mechanism as well as miRNA networks majorly affecting five different ADs namely rheumatoid arthritis (RA), type 1 diabetes, multiple sclerosis (MS), systemic lupus erythematosus (SLE) and inflammatory bowel disorder (IBD) thereby providing novel miRNA‐based theranostic interventions.

Results & Discussion

Pertaining to the differential expression of miRNA attributed in target tissues and cellular bodies of innate and adaptive immunity, a paradigm of scientific expeditions suggests an optimistic correlation between immunogenic dysfunction and miRNA alterations.

Conclusion

Therefore, it is not astonishing that dysregulations in miRNA expression patterns are now recognized in a wide spectrum of disorders, establishing themselves as potential biomarkers and therapeutic targets. Owing to its theranostic potencies, miRNA targets have been widely utilized in the development of biosensors and other therapeutic molecules originating from the same.
Patient and family experiences of lysosomal storage diseases in Canada: A qualitative interview study
Authors: Awada Nahya , Holcik Martin
Published: December 2023

Canadian 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

Objective

Olfactory 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 Design

Cross‐sectional analysis

Setting

FAERS database.

Methods

The 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.

Results

Our 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]).

Conclusion

Pharmacovigilance 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

Optimal 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

In 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.
Fetal growth analysis from ultrasound videos based on different biometrics using optimal segmentation and hybrid classifier
Authors: Devisri B. , Kavitha M.
Published: December 2023

Birth defects and their associated deaths, high health and financial costs of maternal care and associated morbidity are major contributors to infant mortality. If permitted by law, prenatal diagnosis allows for intrauterine care, more complicated hospital deliveries, and termination of pregnancy. During pregnancy, a set of measurements is commonly used to monitor the fetal health, including fetal head circumference, crown‐rump length, abdominal circumference, and femur length. Because of the intricate interactions between the biological tissues and the US waves mother and fetus, analyzing fetal US images from a specialized perspective is difficult. Artifacts include acoustic shadows, speckle noise, motion blur, and missing borders. The fetus moves quickly, body structures close, and the weeks of pregnancy vary greatly. In this work, we propose a fetal growth analysis through US image of head circumference biometry using optimal segmentation and hybrid classifier. First, we introduce a hybrid whale with oppositional fruit fly optimization (WOFF) algorithm for optimal segmentation of segment fetal head which improves the detection accuracy. Next, an improved U‐Net design is utilized for the hidden feature (head circumference biometry) extraction which extracts features from the segmented extraction. Then, we design a modified Boosting arithmetic optimization (MBAO) algorithm for feature optimization to selects optimal best features among multiple features for the reduction of data dimensionality issues. Furthermore, a hybrid deep learning technique called bi‐directional LSTM with convolutional neural network (B‐LSTM‐CNN) for fetal growth analysis to compute the fetus growth and health. Finally, we validate our proposed method through the open benchmark datasets are HC18 (Ultrasound image) and oxford university research archive (ORA‐data) (Ultrasound video frames). We compared the simulation results of our proposed algorithm with the existing state‐of‐art techniques in terms of various metrics.
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

Constructing 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

Diabetic 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

Titin, 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

Many 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.