bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole Exome Sequencing and Panel-Based Analysis in 176 Spanish Children with Neurodevelopmental Disorders: Focus on Autism Spectrum Disorder and/or Intellectual Disability/Global Developmental Delay
Authors: Sánchez Suárez Ariadna , Martínez Menéndez Beatriz , Escolar Escamilla Eduardo , Martínez Sarries Francisco J. , Esparza Garrido Miren Iranzu , Gil-Fournier Belén , Ramiro León Soraya , Rubio Gribble Bárbara , Quesada Espinosa Juan F. , Alcaraz Romero Andrés J.
Published: October 2024

Background: Neurodevelopmental disorders (NDDs) represent a significant challenge in pediatric genetics, often requiring advanced diagnostic tools for the accurate identification of genetic variants. Objectives: To determine the diagnostic yield of whole exome sequencing (WES) with targeted gene panels in children with neurodevelopmental disorders (NDDs). Methods: This observational, prospective study included a total of 176 Spanish-speaking pediatric patients with neurodevelopmental disorders (NDDs), encompassing intellectual disability (ID), global developmental delay (GDD), and/or autism spectrum disorder (ASD). Participants were recruited from January 2019 to January 2023 at a University Hospital in Madrid, Spain. Clinical and sociodemographic variables were recorded, along with genetic study results. The age range of the subjects was 9 months to 16 years, and the percentage of males was 72.1%. The diagnostic yield of whole exome sequencing (WES) was calculated both before and after parental testing via Sanger DNA sequencing. Results: The study included 176 children: 67 (38.1%) with ID, 62 (35.2%) with ASD, and 47 (26.7%) with ASD + ID. The diagnostic yield of proband-only exome sequencing was 12.5% (22/176). By group, the diagnostic yield of proband-only exome sequencing was 3.2% in the ASD, 12.7% in the ASD + ID, and 20.8% in the ID group. Variants of uncertain significance (VUS) were found in 39.8% (70/176). After parental testing, some variants were reclassified as “likely pathogenic”, increasing the diagnostic yield by 4.6%, with an overall diagnostic yield of 17.1%. Diagnostic yield was higher in patients with syndromic ID (70.6%% vs. 29.4%; p = 0.036). Conclusions: A sequential approach utilizing WES followed by panel-based analysis, starting with the index case and, when appropriate, including the parents, proves to be a cost-effective strategy. WES is particularly suitable for complex conditions, as it allows for the identification of potentially causative genes beyond those covered by targeted panels, providing a more comprehensive analysis. Including parental testing enhances the diagnostic yield and improves accuracy, especially in cases with variants of uncertain significance (VUS), thereby advancing our understanding of NDDs.
An Integrated Approach to the Regional Estimation of Soil Moisture
Authors: Sánchez-Fernández Luis Pastor , Flores-Carrillo Diego Alberto , Sánchez-Pérez Luis Alejandro
Published: October 2024

Automatic or smart irrigation systems benefit irrigation water management. However, measurement sensor networks in automatic irrigation systems are complex, and maintenance is essential. Regional soil moisture estimation avoids the multiple measurements necessary when deploying an irrigation system. In this sense, a fuzzy estimation approach based on decision-making (FEADM) has been used to obtain soil moisture point estimates. However, FEADM requires intelligent weather adjustment based on spatial features (IWeCASF) to perform regional soil moisture estimation. The IWeCASF-FEADM integrated approach for regional soil moisture estimation is developed in this work. IWeCASF provides the inputs for FEADM. FEADM is performed R times; R is the number of checkpoints at which a point estimate is obtained. In this way, regional estimation is achieved when the set of R soil moisture point estimates is completed. Additionally, IWeCASF-FEADM considers the irrigation water records, which are not included in either method individually. This method can detect when the soil moisture is deficient in a region, allowing actions to prevent water stress. This regional estimation reduces an irrigation system’s operational and maintenance complexity. This integrated approach has been tested over several years by comparing the results of regional soil moisture estimation with measurements obtained at many points in the study region.
Distribution of Subsurface Nitrogen and Phosphorus from Different Irrigation Methods in a Maize Field
Authors: Xie Gang , Su Zhihui , Fu Yiming , Li Jing , Mao Deqiang , Wang Shaowei
Published: October 2024

With the advancement of agricultural technology, most crop cultivation adopts water-saving techniques to improve nutrient utilization efficiency. However, limited research has been carried out on the applicability of water-saving techniques for summer maize in the Shandong Province, and it is necessary to assess the risk of nutrient loss in farmland when applying these technologies. This study investigated the distribution of nitrogen and phosphorus under different irrigation methods and planting patterns through soil and water samples. It included sprinkler irrigation (SI), drip irrigation (DI), and subsurface irrigation (SUBI). Different planting patterns, i.e., monoculture (MP) and intercropping pattern (IP), were also selected in the SI zones. The results show variations in soil nitrogen distribution within the layers between 0.9 and 4.5 m, with a pronounced trend of NO3−-N accumulating in deeper layers in the SI zone. Under SI conditions, the IP effectively reduces the nutrient accumulation around the shallow root zone while controlling the accumulation of nitrogen in deep layers. The Olsen-P accumulation in each zone would increase after the accumulation ratio decreased. Compared with MP, the depth interval of the accumulation ratio mutation was shallower in the IP. The trend of NO3−-N accumulation in deep layers is consistent with that of nitrogen concentration in groundwater. Phosphorus that is accumulated in the deep layers is not easily leached into groundwater. In conclusion, these findings can provide basic information for irrigation management in existing cropping systems.
The Association between Post-Traumatic Stress Disorder and Problematic Alcohol and Cannabis Use in a Multi-Ethnic Cohort in The Netherlands: The HELIUS Study
Authors: Kühner Christin , Will Joanne P. , Lortye Sera A. , Galenkamp Henrike , Lok Anja , van Zuiden Mirjam , Arntz Arnoud R. , Thomaes Kathleen , Goudriaan Anna E. , de Waal Marleen M.
Published: October 2024

(1) Background: Ethnic minorities exhibit a higher prevalence of post-traumatic stress disorder (PTSD), while results for problematic substance use among ethnic groups remain mixed. PTSD and problematic substance use often co-occur; however, the impact of ethnicity on this association has not yet been investigated. (2) Methods: Self-report data on problematic alcohol/cannabis use (AUDIT/CUDIT) and presence of severe PTSD symptoms (PSS-SR) of N = 22,841 participants of Dutch (n = 4610), South-Asian Surinamese (n = 3306), African Surinamese (n = 4349), Ghanaian (n = 2389), Turkish (n = 3947), and Moroccan (n = 4240) origin were available from the HELIUS study. (3) Results: We found a positive association between the presence of severe PTSD symptoms and problematic alcohol and cannabis use. Ethnicity did not moderate the association between the presence of severe PTSD symptoms and problematic alcohol/cannabis use. (4) Conclusions: We demonstrated the relationship between the presence of severe PTSD symptoms and problematic alcohol/cannabis use in a multi-ethnic sample. The relationship between the presence of severe PTSD symptoms and problematic alcohol/cannabis use was similar between ethnic groups. We recommend screening for PTSD symptoms in those exhibiting problematic substance use and vice versa, regardless of ethnic background.
Resilience Mechanisms and Coping Strategies for Forcibly Displaced Youth: An Exploratory Rapid Review
Authors: Alamgir Akm , Kyriakides Christopher , Johnson Andrew , Abeshu Gemechu , Bahri Bay , Abssy Miles
Published: October 2024

Context: The global escalation of conflict, violence, and human rights violations sets a pressing backdrop for examining the resilience of forcibly displaced youth (FDY) in Canada. This study aims to unpack the multifaceted challenges and resilience mechanisms of FDY, focusing on their health, well-being, and integration into host communities. It seeks to identify current models of resilience, understand the factors within each model, and highlight gaps and limitations. Methodology: Using a university librarian-supported structured search strategy, this exploratory rapid review searched literature from Ovid Medline and open-source databases, published in English between January 2019 and January 2024, that fit specific inclusion criteria. The eligible articles (N = 12 out of 4096) were charted and analyzed by two student researchers with the Principal Investigator (PI). Charted data were analyzed thematically. Results: The selected studies captured diverse geographical perspectives, resilience models (such as Ungar’s ecological perspective and Masten’s resilience developmental models), as well as protective and promotive frameworks. Key findings indicate the complexity of resilience influenced by individual, familial, societal, and cultural factors. Each model offers insights into the dynamic interplay of these influences on FDY’s resilience. However, these models often fall short of addressing the nuances of cultural specificity, the impact of trauma, and the intersectionality of FDY’s identities. Conclusions: Recognizing the diverse and evolving nature of FDY’s coping mechanisms, this study advocates for a culturally appropriate approach to resilience that integrates an intersectionality framework of individual attributes and culturally sensitive models.
Deep Learning Application for Biodiversity Conservation and Educational Tourism in Natural Reserves
Authors: Flórez Marco , Becerra Oscar , Carrillo Eduardo , Villa Manny , Álvarez Yuli , Suárez Javier , Mendes Francisco
Published: October 2024

Natural reserves, such as the Santurbán Moor in Colombia, are ecologically important but face significant threats from activities like mining and agriculture. Preserving biodiversity in these ecosystems is essential for maintaining ecological balance and promoting sustainable tourism practices. Identifying plant species in these reserves accurately is challenging due to environmental variability and species similarities, complicating conservation efforts and educational tourism promotion. This study aims to create and assess a mobile application based on deep learning, called FloraBan, to autonomously identify plant species in natural reserves, enhancing biodiversity conservation and encouraging sustainable and educational tourism practices. The application employs the EfficientNet Lite4 model, trained on a comprehensive dataset of plant images taken in various field conditions. Designed to work offline, the application is particularly useful in remote areas. The model evaluation revealed an accuracy exceeding 90% in classifying plant images. FloraBan was effective under various lighting conditions and complex backgrounds, offering detailed information about each species, including scientific name, family, and conservation status. The ability to function without internet connectivity is a significant benefit, especially in isolated regions like natural reserves. FloraBan represents a notable improvement in the field of automated plant identification, supporting botanical research and efforts to preserve biodiversity in the Santurbán Moor. Additionally, it encourages educational and responsible tourism practices, which align with sustainability goals, providing a useful tool for both tourists and conservationists.
Microbial Gatekeepers of Fertility in the Female Reproductive Microbiome of Cattle
Authors: Adnane Mounir , Chapwanya Aspinas
Published: October 2024

This review paper delves into the intricate relationship between the genital microbiome and fertility outcomes in livestock, with a specific focus on cattle. Drawing upon insights derived from culture-independent metagenomics studies, the paper meticulously examines the composition and dynamics of the genital microbiome. Through advanced techniques such as high-throughput sequencing, the review illuminates the temporal shifts in microbial communities and their profound implications for reproductive health. The analysis underscores the association between dysbiosis—an imbalance in microbial communities—and the development of reproductive diseases, shedding light on the pivotal role of microbial gatekeepers in livestock fertility. Furthermore, the paper emphasizes the need for continued exploration of uncharted dimensions of the female reproductive microbiome to unlock new insights into its impact on fertility. By elucidating the complex interplay between microbial communities and reproductive health, this review underscores the importance of innovative strategies aimed at enhancing fertility and mitigating reproductive diseases in livestock populations.
Polyamines in Plant–Pathogen Interactions: Roles in Defense Mechanisms and Pathogenicity with Applications in Fungicide Development
Authors: Yi Qi , Park Min-Jeong , Vo Kieu Thi Xuan , Jeon Jong-Seong
Published: October 2024

Polyamines (PAs), which are aliphatic polycationic compounds with a low molecular weight, are found in all living organisms and play essential roles in plant–pathogen interactions. Putrescine, spermidine, and spermine, the most common PAs in nature, respond to and function differently in plants and pathogens during their interactions. While plants use certain PAs to enhance their immunity, pathogens exploit PAs to facilitate successful invasion. In this review, we compile recent studies on the roles of PAs in plant–pathogen interactions, providing a comprehensive overview of their roles in both plant defense and pathogen pathogenicity. A thorough understanding of the functions of PAs and conjugated PAs highlights their potential applications in fungicide development. The creation of new fungicides and compounds derived from PAs demonstrates their promising potential for further research and innovation in this field.
Deletion of Slc1a4 Suppresses Single Mauthner Cell Axon Regeneration In Vivo through Growth-Associated Protein 43
Authors: Li Keqiang , Fan Dinggang , Zhou Junhui , Zhao Ziang , Han Along , Song Zheng , Tang Xiahui , Hu Bing
Published: October 2024

Spinal cord injury (SCI) is a debilitating central nervous system (CNS) disorder that leads to significant motor and sensory impairments. Given the limited regenerative capacity of adult mammalian neurons, this study presents an innovative strategy to enhance axonal regeneration and functional recovery by identifying a novel factor that markedly promotes axonal regeneration. Employing a zebrafish model with targeted single axon injury in Mauthner cells (M-cells) and utilizing the Tg (Tol056: EGFP) transgenic line for in vivo monitoring, we investigate the intrinsic mechanisms underlying axonal regeneration. This research specifically examines the role of amino acid transport, emphasizing the role of the solute carrier 1A4 amino acid transporter in axonal regeneration. Our findings demonstrate that Slc1a4 overexpression significantly enhances axonal regeneration in M-cells, whereas Slc1a4 deficiency impedes this process, which is concomitant with the downregulation of the P53/Gap43 signaling pathway. By elucidating the fundamental role of Slc1a4 in axonal regeneration and uncovering its underlying mechanisms, this study thus provides novel insights into therapeutic strategies for SCI.
Trp53 Deletion Promotes Exacerbated Colitis, Facilitates Lgr5+ Cancer Stem Cell Expansion, and Fuels Tumorigenesis in AOM/DSS-Induced Colorectal Cancer
Authors: Cunha Anderson F. , Delou João M. , Barbosa Pedro S. , Conceição Julia S. M. , Souza Karen C. S. , Chagas Vera , Soletti Rossana C. , de Souza Heitor S. P. , Borges Helena L.
Published: October 2024

Colorectal cancer CRC remains one of the leading causes of cancer-related deaths worldwide, with chronic intestinal inflammation identified as a major risk factor. Notably, the tumor suppressor TP53 undergoes mutation at higher rates and earlier stages during human inflammation-driven colon tumorigenesis than in sporadic cases. We investigated whether deleting Trp53 affects inflammation-induced tumor growth and the expression of Lgr5+ cancer stem cells in mice. We examined azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumorigenesis in wild-type Trp53 (+/+), heterozygous (+/−), and knockout (−/−) mice. Trp53−/− mice showed increased sensitivity to DSS colitis and earlier accelerated tumorigenesis with 100% incidence. All groups could develop invasive tumors, but knockouts displayed the most aggressive features. Unlike wild-type CRC, knockouts selectively showed increased populations of Lgr5+ colon cancer stem-like cells. Trp53 loss also boosted laminin, possibly facilitating the disruption of the tumor border. This study highlights how Trp53 deletion promotes the perfect storm of inflammation and stemness, driving colon cancer progression. Trp53 deletion dramatically shortened AOM/DSS latency and improved tumor induction efficiency, offering an excellent inflammation-driven CRC model.
Environmental Driving of Adaptation Mechanism on Rumen Microorganisms of Sheep Based on Metagenomics and Metabolomics Data Analysis
Authors: He Haiying , Fang Chao , Liu Lingling , Li Mingming , Liu Wujun
Published: October 2024

Natural or artificial selection causes animals to adapt to their environment. The adaptive changes generated by the rumen population and metabolism form the basis of ruminant evolution. In particular, the adaptive drive for environmental adaptation reflects the high-quality traits of sheep that have migrated from other places or have been distant from their origins for a long time. The Hu sheep is the most representative sheep breed in the humid and low-altitude environments (Tai Lake region) in East Asia and has been widely introduced into the arid and high-altitude environments (Tibetan Plateau and Hotan region), resulting in environmental adaptive changes in the Hu sheep. In this study, a joint analysis of the rumen microbial metagenome and metabolome was conducted on Hu sheep from different regions (area of origin and area of introduction) with the objective of investigating the quality traits of Hu sheep and identifying microorganisms that influence the adaptive drive of ruminants. The results demonstrated that the growth performance of Hu sheep was altered due to changes in rumen tissue and metabolism following their introduction to the arid area at relatively high altitude. Metagenomic and metabolomic analyses (five ramsper area) revealed that 3580 different microorganisms and 732 different metabolites were identified in the rumen fluid of arid sheep. Among these, the representative upregulated metabolites were 4,6-isocanedione, methanesulfonic acid and N2-succinyl-L-arginine, while the dominant microorganism was Prevotella ruminicola. The downregulated metabolites were identified as campesterol, teprenone and dihydroclavaminic acid, while the disadvantaged microorganisms were Dialister_succinatiphilus, Prevotella_sp._AGR2160, Prevotella_multisaccharivorax and Selenomonas_bovis. The results of the Pearson analysis indicated that the rumen microbiota and metabolite content of sheep were significantly altered and highly correlated following their relocation from a humid lowland to an arid upland. In particular, the observed changes in rumen microorganisms led to an acceleration of body metabolism, rendering sheep highly adaptable to environmental stress. Prevotella_ruminicola was identified as playing an important role in this process. These findings provide insights into the environmental adaptation mechanisms of sheep.
Graph Neural Networks: A Bibliometric Mapping of the Research Landscape and Applications
Authors: da Silva Annielle Mendes Brito , Ferreira Natiele Carla da Silva , Braga Luiza Amara Maciel , Mota Fabio Batista , Maricato Victor , Alves Luiz Anastacio
Published: October 2024

Graph neural networks (GNNs) are deep learning algorithms that process graph-structured data and are suitable for applications such as social networks, physical models, financial markets, and molecular predictions. Bibliometrics, a tool for tracking research evolution, identifying milestones, and assessing current research, can help identify emerging trends. This study aims to map GNN applications, research directions, and key contributors. An analysis of 40,741 GNN-related publications from the Web Science Core Collection reveals a rising trend in GNN publications, especially since 2018. Computer Science, Engineering, and Telecommunications play significant roles in GNN research, with a focus on deep learning, graph convolutional networks, neural networks, convolutional neural networks, and machine learning. China and the USA combined account for 76.4% of the publications. Chinese universities concentrate on graph convolutional networks, deep learning, feature extraction, and task analysis, whereas American universities focus on machine learning and deep learning. The study also highlights the importance of Chemistry, Physics, Mathematics, Imaging Science & Photographic Technology, and Computer Science in their respective knowledge communities. In conclusion, the bibliometric analysis provides an overview of GNN research, showing growing interest and applications across various disciplines, and highlighting the potential of GNNs in solving complex problems and the need for continued research and collaboration.
Impact of Aggregation Pheromone Traps on Spatial Distribution of Halyomorpha halys Damage in Apple Orchards
Authors: Carnio Veronica , Favaro Riccardo , Preti Michele , Angeli Sergio
Published: October 2024

Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) is an invasive pest causing significant damage to tree crops. Our study examined the impact of newly designed aggregation pheromone-baited ‘mini–sailboat’ (MSB) traps for controlling H. halys and its effect on the spatial distribution of fruit damage. Four replicates of four traps, with a total of 16 MSB traps, were placed along a 1.3 km border of apple orchards, concentrating the traps on one side of the orchards. A fruit damage assessment for incidence and severity was conducted at increasing distances from the orchard border where the traps were placed, encompassing 107 assessment points. Our study showed that deploying MSB traps along the orchard border significantly increased fruit damage within the first 45 m compared to control plots without traps. However, beyond the first 45 m from the border, there was a significant reduction in damage incidence. In the treated plots, 50% of the damage occurred within 26 m of the traps, while in control plots, within 85 m. Shifting the fruit damage pattern means restricting the pests lingering in a narrow strip near the MSB traps, which paves the way for improved techniques to restructure the crop perimeter.
Buzzing towards Resilience: Investigating the Spatial Alignment of the Desert Pallid Bee, Centris pallida, and Its Host Plants in Response to Climate Change
Authors: Cruz Terese Maxine P. , Buchmann Stephen L. , Prudic Kathleen L.
Published: October 2024

Wild bees are vital for the pollination of native plants and crops, providing essential ecosystem services. Climate change is known to impact biodiversity and species distributions, but insects adapted to desert ecosystems may exhibit unique physiological, behavioral, and evolutionary responses. The desert pallid bee (C. pallida), a solitary bee native to the arid southwestern United States and northern Mexico, primarily forages on yellow palo verde (P. microphylla), blue palo verde (P. florida), and desert ironwood (O. tesota). This study used MaxEnt to estimate the current and projected geographical overlap of suitable habitats for C. pallida and its host plants. Here, we used MaxEnt to estimate the current and forecasted overlapping geographically suitable habitat of C. pallida with all three host plants. We forecasted potential environmentally suitable areas for each species to the year 2040 using the current distribution model and climate projections with moderate CO2 levels. We found a continued spatial alignment in the suitable area of the bee and its host plants with a 70% increase in the range overlap area, though shifted to higher average altitudes and a slight northern expansion. These findings may provide insight to stakeholders on the conservation needs of desert-dwelling pollinators.
Bicuspid Aortic Valve in Children and Young Adults for Cardiologists and Cardiac Surgeons: State-of-the-Art of Literature Review
Authors: Nappi Francesco , Avtaar Singh Sanjeet Singh , de Siena Paolo M.
Published: October 2024

Bicuspid aortic valve disease is the most prevalent congenital heart disease, affecting up to 2% of the general population. The presentation of symptoms may vary based on the patient’s anatomy of fusion, with transthoracic echocardiography being the primary diagnostic tool. Bicuspid aortic valves may also appear with concomitant aortopathy, featuring fundamental structural changes which can lead to valve dysfunction and/or aortic dilatation over time. This article seeks to give a comprehensive overview of the presentation, treatment possibilities and long-term effects of this condition. The databases MEDLINE, Embase, and the Cochrane Library were searched using the terms “endocarditis” or “bicuspid aortic valve” in combination with “epidemiology”, “pathogenesis”, “manifestations”, “imaging”, “treatment”, or “surgery” to retrieve relevant articles. We have identified two types of bicuspid aortic valve disease: aortic stenosis and aortic regurgitation. Valve replacement or repair is often necessary. Patients need to be informed about the benefits and drawbacks of different valve substitutes, particularly with regard to life-long anticoagulation and female patients of childbearing age. Depending on the expertise of the surgeon and institution, the Ross procedure may be a viable alternative. Management of these patients should take into account the likelihood of somatic growth, risk of re-intervention, and anticoagulation risks that are specific to the patient, alongside the expertise of the surgeon or centre. Further research is required on the secondary prevention of patients with bicuspid aortic valve (BAV), such as lifestyle advice and antibiotics to prevent infections, as the guidelines are unclear and lack strong evidence.
Descemet Membrane Endothelial Keratoplasty Graft Preparation Using the Liquid Bubble Technique with Subtrabecular Hydrodissection: A Retrospective Real-Life Study
Authors: Blavakis Emmanouil , Kecik Mateusz , Panos Georgios D. , Thumann Gabriele , Massa Horace
Published: October 2024

Background: Techniques for the preparation of grafts for Descemet membrane endothelial keratoplasty (DMEK) can be classified into those that involve the manual dissection of the Descemet membrane (DM) and those that use an injection of a liquid or a gas to achieve a separation of the DM from the posterior corneal stroma. The purpose of this study was to evaluate the efficiency of the liquid bubble technique. Methods: The success rate of the technique was calculated retrospectively using the operating reports. Video files for each graft preparation were retrieved and the time, number of injections, and number of injections sites required for the hydrodissection were measured. The number of cases in which a manual dissection of the Descemet membrane was necessary was recorded. Information on donor age and graft preservation time were retrieved from the eye bank file. Results: In 58 cases, the success rate was 98.3%. In the 28 procedures where a video was available, the median time for hydrodissection was 4.4 min. The median number of injection sites was 2, with a median number of injections of 3.5. Manual dissection as a rescue technique was performed in 25% of cases, with one case resulting in graft tears. The mean graft diameter was 7.6 mm. The mean donor age was 66 years, and the mean graft storage time was 22 days. Conclusions: The liquid bubble technique can be a fast and valuable choice for DMEK graft preparation, especially in centers where the tissue is prepared in the operating theater.
No Effect of Low-Dose Glucocorticoid Maintenance Therapy on Damage in SLE Patients in Prolonged Remission: A Propensity Score Analysis of the Longitudinal Lupus-Cruces-Bordeaux Inception Cohort
Authors: Ruiz-Irastorza Guillermo , Paredes-Ruiz Diana , Dueña-Bartolome Luis , Hernandez-Negrin Halbert , Moreno-Torres Victor , Richez Christophe , Lazaro Estibaliz
Published: October 2024

Background/Objectives: Prolonged remission on low-dose glucocorticoids (GC) is a main goal in patients with systemic lupus erythematosus (SLE). The aim of this study is to assess whether GC ≤ 5 mg/d increases the risk of damage accrual in patients with SLE in prolonged remission. Methods: Observational study of routine clinical care data of the inception Lupus Cruces-Bordeaux cohort. Only patients in DORIS remission during five consecutive yearly visits were included. The endpoint was damage accrual during the 5-year follow-up, either global or specific damage: GC-induced, cardiovascular (CV), lupus and other. Patients no longer on GC therapy by year 5 (GC5-Off) were compared with those who continued GC therapy (GC5-On). Comparisons were made by Cox and Poisson regressions, which were adjusted with propensity score (PE) in order to control for confounding by indication. Results: 132 patients were included, 56 in the GC5-On and 76 in the GC5-Off groups. All patients were on GC ≤ 5 mg/d for the whole follow-up, the mean prednisone dose in the GC5-On group being 2.96 mg/d during the whole study period and 2.6 mg/d during the 5th year. Fourteen patients (10.6%) accrued damage. More patients in the GC5-On group accrued global damage, 16% vs. 7% in the GC5-Off group, p = 0.08, mainly at CV domains (7% vs. 1%, respectively, p = 0.16). In the PS-adjusted Cox and Poisson regressions, the GC5-On group was not significantly associated with global (p = 0.39) or CV damage accrual (p = 0.62), nor with the absolute (p = 0.40) or CV-restricted final SDI scores (p = 0.63). The C-index of the propensity score model was 0.79. Conclusions: Maintaining doses of prednisone < 5 mg/d in lupus patients in prolonged remission is not associated with an increased risk of damage accrual.
Impact of Intraoperative Blood Transfusion on Cerebral Injury in Pediatric Patients Undergoing Congenital Septal Heart Defect Surgery
Authors: Ivkin Artem , Grigoriev Evgeny , Mikhailova Alena
Published: October 2024

Background: The components of donor blood themselves have the potential to initiate a systemic inflammatory response and exacerbate neuroinflammation, resulting in subsequent cerebral injury. The aim of this study was to establish the role of transfusion in the development of cerebral injury during the correction of congenital heart defects in children. Material and Methods: A total of 78 patients aged from 1 to 78 months, with body weights ranging from 3.3 to 21.5 kg, were investigated. Biomarkers of cerebral injury and systemic inflammatory response were studied at three time points. First: prior to the surgical intervention. Second: after the completion of cardiopulmonary bypass. Third: 16 h after the conclusion of the surgery. Results: The strongest correlation was found for S-100-β protein with the volume of transfusion at the second (Rho = 0.48, p = 0.00065) and third time points (Rho = 0.36, p = 0.01330). Neuron-specific enolase demonstrated a similar trend: Rho = 0.41 and p = 0.00421 after the completion of cardiopulmonary bypass. Conclusions: The use of red blood cell suspension and its dosage per kilogram of body weight correlated with the biomarkers of cerebral injury and systemic inflammatory response with moderate to significant strength.
Anakinra-Dependent Recurrent Pericarditis: The Role of the R202Q Variant of the MEFV Gene
Authors: Andreis Alessandro , Dossi Federica Currò , De Ferrari Gaetano Maria , Alunni Gianluca , Imazio Massimo
Published: October 2024

Background: the role of the R202Q (c.605G>A, p.Arg202Gln) missense variant of the MEFV gene has been debated as either a benign polymorphism or a potentially pathogenic mutation. We report and discuss here the case of a young female with corticosteroid-dependent recurrent pericarditis carrying the homozygous R202Q variant, exhibiting distinctive clinical features possibly influenced by this genetic variant. Methods: a 30-year-old woman with a previous diagnosis of cancer and recent respiratory infection presented with severe pleuritic chest pain, hypotension, tachycardia, and fever. Initial diagnostic evaluation indicated cardiac tamponade, and emergent pericardiocentesis was performed. Despite initial treatment with NSAIDs, colchicine, and corticosteroids, the patient experienced multiple recurrences. Genetic testing identified homozygous R202Q variant in the MEFV gene. Given the corticosteroid dependency and recurrent nature of her condition, IL-1 inhibitor anakinra was introduced, leading to significant improvement, although tapering below 150 mg per week failed to prevent recurrences. Results: the introduction of anakinra resulted in rapid symptom relief and resolution of pericardial effusion. However, attempts to taper or discontinue anakinra led to pericarditis recurrences. Ultimately, a maintenance dose of 50 mg every three days was established, which maintained remission for 18 months without recurrence. Despite multiple tapering attempts, further reduction in anakinra dosage was unsuccessful without triggering relapses. Conclusions: the R202Q variant, although typically considered benign, may contribute to an autoinflammatory phenotype resembling familial Mediterranean fever. This case underscores the potential pathogenicity of the homozygous R202Q variant in recurrent pericarditis and its responsiveness to IL-1 inhibition. In patients with corticosteroid-dependent recurrent pericarditis, genetic testing for the R202Q variant should be considered when anti-IL-1 drugs cannot be withdrawn. Further studies are warranted to elucidate the variant’s role in pericardial inflammation and guide personalized treatment strategies.
Symptomatic Vitreous Opacities: Exploring the Mismatch between Clinical Observation of Vitreous Alterations and Self-Reported Symptoms
Authors: Bamonte Giulio , Iodice Clemente Maria , Mastropasqua Rodolfo , Van Dijk Elon H. C. , Appeltans Andrea , Cicinelli Maria Vittoria , Menean Matteo , Ten Tusscher Marcel , Harmer Stuart W. , Marolo Paola , Borrelli Enrico , Reibaldi Michele , Panos Georgios D. , Motta Lorenzo
Published: October 2024

Objectives: To assess the mismatch between the clinical observation of vitreous alterations and self-reported symptoms in young patients complaining of symptomatic vitreous opacities (SVO). Methods: The ophthalmic medical records of young patients presenting primarily with SVO were retrospectively evaluated. Symptoms severity was assessed using a questionnaire. The status of the vitreous body was examined with indirect ophthalmoscopy at the slit-lamp and classified according to an ad hoc severity scale. Results: Sixty eyes of thirty otherwise healthy patients (median age: 32.5 (IQR: 29.0–37.0) years old) complaining of SVO (median duration: 38 months; interquartile range: 18–84 months) were enrolled. SVO was rated as severe by 50% of participants, affecting all the activities explored in the questionnaire. Twenty-three patients (76.6%) reported SVO-related depression and/or anxiety, for which eleven patients (36.6%) were or had been using medication. Fifty-eight eyes (96.6%) showed no evidence of (or minimal) vitreous opacity, while two eyes (3.3%) were found to have significant vitreous opacity. No significant inter-gender differences (p > 0.05) and no significant differences (p > 0.05) were found between the severity of vitreous opacity and patients’ reported symptoms nor with their psychological status and medication use. Conclusions: Severe discomfort related to the perception of vitreous floaters exists in young patients whose vitreous gel examination is unremarkable or shows only minor alterations. We believe this discrepancy can be explained by optical anisotropy; significant forward-scattering of light, which results in floater symptoms; and reduced back reflection, which limits the clinical observation.
Accuracy of Infrared Thermography in Diagnosing Breast Cancer-Related Lymphedema
Authors: Gomes Vanessa Maria da Silva Alves , Brioschi Marcos Leal , Silva Ana Rafaela Cardozo da , Tenório Naiany , Oliveira Laura Raynelle Patriota , Silva Ana Claúdia Souza da , Maia Juliana Netto , Dantas Diego
Published: October 2024

Background/Objectives: Infrared thermography (IRT) is an imaging technique used in clinical practice to detect changes in skin temperature caused by several dysfunctions, including breast cancer-related lymphedema (BCRL). Thus, the present study aimed to assess the reproducibility and accuracy of IRT in diagnosing BCRL. Methods: This cross-sectional study included participants who underwent a unilateral mastectomy and used indirect volumetry for lymphedema detection. IRT analysis was recorded in four positions, analyzing maximum, mean, and minimum temperatures, as well as the temperature differences between the upper limbs. The analysis encompassed reliability, agreement, accuracy, and the establishment of cut-off points for sensitivity and specificity. A total of 88 upper limbs were included; 176 thermograms were captured, and 1056 regions of interest were analyzed. Results: IRT presented excellent intra- and inter-rater reproducibility and reliability with excellent intraclass correlation coefficient values (0.99 to 1.00). In addition, this assessment reached a sensitivity of 85% and a specificity of 56%; the cut-off point considered a temperature difference of −0.45 °C. Conclusions: IRT was a reliable and reproducible assessment, and the temperature difference between the upper limbs evidenced moderate accuracy. Thus, IRT is recommended as a complementary technique for detecting BCRL.
Endothelin Inhibitors in Chronic Kidney Disease: New Treatment Prospects
Authors: Rakotoarison Agata , Kepinska Marta , Konieczny Andrzej , Władyczak Karolina , Janczak Dariusz , Hałoń Agnieszka , Donizy Piotr , Banasik Mirosław
Published: October 2024

The endothelin system is reported to play a significant role in glomerular and tubulointerstitial kidney disease. In the kidney, endothelins are produced in mesangial cells and the glomerular basement membrane by the endothelium and podocytes. The endothelin system regulates glomerular function by inducing proliferation, increasing permeability and in effect proteinuria, and stimulating inflammation, tubular fibrosis, and glomerular scarring. Endothelin A receptor antagonists have been proven to delay the progression of chronic kidney disease and play a protective role in immunoglobulin A nephropathy, focal segmental glomerulosclerosis, and diabetic nephropathy. There are several ongoing research studies with ETAR antagonists in nondiabetic nephropathy, Alport disease, vasculitis and scleroderma nephropathy, which results are promising. Some reports suggest that the endothelin system might contribute to ischemia–reperfusion injury, acute graft rejection and deterioration of graft function. Endothelin inhibition in renal transplantation and its influence on graft survival is the future direction needing further research. The most frequent side effects associated with ETAR antagonists is fluid retention. Additionally, it should be considered if selective ETAR antagonists therapy needs to be co-administered with sodium-glucose co-transporter 2 inhibitors, renin–angiotensin–aldosterone inhibitors or diuretics and which patients should be recruited to such treatment to minimize the risk of adverse outcomes.
Very Early-Onset IBD-Associated IL-18opathy Treated with an Anti-IL-18 Antibody
Authors: Guha Anthea , Diaz-Pino Rodrigo , Fagbemi Andrew , Hughes Stephen M. , Wynn Robert F. , Lopez-Castejon Gloria , Arkwright Peter D.
Published: October 2024

Background/Objectives: The aetiology of inflammatory bowel disease (IBD), particularly if occurring early in childhood, is a diverse and patient-focused treatment that is required when standard therapy is ineffective. Materials and Methods: A clinical case report is presented of a child with very early-onset IBD (VEOIBD) and evidence of high serum IL-18 responding to anti-IL-18 immunotherapy. Detailed cytokine profiling was performed by ELISA and multiplex assay flow cytometry. Results: A four-year-old girl with recalcitrant VEOIBD from six weeks old due to an IL-18opathy, characterised by high blood IL-18 concentration, responded to therapy with a novel neutralising anti-IL-18 antibody (GSK1070806). After two years of hospitalisation, the child’s systemic inflammation and extensive upper and lower gastrointestinal mucosal ulceration remitted with this cytokine inhibitor, allowing the discontinuation of total parenteral nutrition and the resumption of normal oral intake and daily activities. After 18 months on regular GSK1070806, the patient remains in disease remission. Conclusions: VEOIBD can be associated with evidence of an underlying IL18opathy and responds to anti-IL-18 antibody therapy. IL-18 should be measured in patients with IBD unresponsive to conventional treatments, and, if elevated, anti-IL-18 antibody therapy should be considered as a potential therapy.
Advanced Lung Cancer Inflammation Index as Predictor of All-Cause Mortality in ST-Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Trimarchi Giancarlo , Pizzino Fausto , Lilli Alessio , De Caterina Alberto Ranieri , Esposito Augusto , Dalmiani Stefano , Mazzone Annamaria , Di Bella Gianluca , Berti Sergio , Paradossi Umberto
Published: October 2024

Background: The advanced lung cancer inflammation index (ALI) is an independent prognostic biomarker used to assess inflammation and nutritional status in various cancers, heart failure, and acute coronary syndromes. This study investigates the prognostic significance of ALI in patients experiencing ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), comparing its predictive abilities with the established Neutrophil-Lymphocyte Ratio (NLR). Methods: We conducted a retrospective analysis of 1171 patients from the Matrix Registry, encompassing demographic and clinical data for STEMI cases treated with pPCI, and ALI was determined using the formula [serum albumin (g/dL) × body mass index (kg/m2)]/NLR at the time of hospital admission. The primary outcome was all-cause mortality. Results: Of the 1171 patients, 86 died during the follow-up period. Univariate analysis identified age, female gender, smoking, hypertension, diabetes, prior myocardial infarction (PMI), lower left ventricular ejection fraction (LVEF), and reduced ALI as factors associated with mortality. Multivariate analysis confirmed age (HR: 1.1, 95% CI: 1.05–1.11, p < 0.001) and PMI (HR: 2.4, 95% CI: 1.4–4.3, p = 0.001) as prominent independent predictors, alongside ALI (HR: 0.95, 95% CI: 0.92–0.97, p < 0.001) and LVEF (HR: 0.98, 95% CI: 0.97–0.99, p = 0.04). An ALI cut-off of ≤10 indicated a higher mortality risk (HR: 2.3, 95% CI: 1.5–3.7, p < 0.001). The area under the curve for ALI (0.732) surpassed that for NLR (0.685), demonstrating ALI’s superior predictive capability. Conclusions: ALI is an independent prognostic factor for all-cause mortality in STEMI patients undergoing pPCI, showing greater discriminatory power than NLR, particularly in patients with ALI values ≤ 10, who face a 2.3-fold higher mortality risk.
The Effect of Tele-Continuous Care on Maternal Functioning and Neonatal Perception among Iranian Primiparous Mothers: A Randomized Field Trial Study
Authors: Arang Fatemeh , Barkin Jennifer L. , Farid Malihe , Akbari Kamrani Mahnaz
Published: October 2024

Background/Objectives: New mothers face significant challenges during the postpartum period, which can impact their maternal performance. This study aimed to assess the effect of tele-continuous midwifery care on maternal functioning and neonatal perception in first-time Iranian mothers. Methods: A randomized controlled field trial was conducted from January to May 2023 on 48 first-time mothers in the postpartum ward at Arash Women’s Hospital, Tehran. Participants were randomly assigned to either an intervention or control group. The intervention group received tele-continuous care for six weeks postpartum, while the control group received standard care. The Barkin Index of Maternal Functioning (BIMF) and the Neonatal Perception Inventory (NPI) were used to collect data in the second and sixth weeks after delivery. Data were analyzed using SPSS 26. Results: The mean age was 26.2 ± 4.8 years in the intervention group and 28.0 ± 6.1 years in the control group. An independent t-test revealed a significant difference in maternal functioning (BIMF score) between the intervention and control groups by the sixth week postpartum (p < 0.0001). A significant improvement in BIMF scores was observed within the intervention group from the second to the sixth week (p = 0.007). However, the McNemar’s test on the NPI showed no significant difference in the proportions of negative and positive maternal perceptions within the intervention group (p = 0.219) and in the control group (p = 0.508). Conclusions: Tele-continuous midwifery care effectively enhances maternal functioning during the vulnerable postpartum period, highlighting the necessity of ongoing support for new mothers.
Association between Dietary Antioxidants and Atherosclerotic Cardiovascular Disease in South Korea: Insights from a Comprehensive Cross-Sectional Analysis
Authors: Kim Jong-Ho , Lee Myeong Eun , Hwang Sung-Mi , Lee Jae-Jun , Kwon Young-Suk
Published: October 2024

Background/Objectives: The multifactorial nature of atherosclerotic cardiovascular disease (ASCVD) implicates genetic, environmental, and dietary habits. Antioxidants found in foods have garnered attention for their potential role in mitigating ASCVD risk by combating oxidative stress. This study seeks to confirm the findings of previous research through a large-scale cross-sectional analysis performed in a unique population with Korea National Health and Nutrition Examination Survey data to explore the association between the composite dietary antioxidant index (CDAI) and ASCVD prevalence among middle- and old-aged individuals in South Korea. Methods: This study includes data from 2016 to 2021. The CDAI was calculated based on nutrition intake, including zinc, beta-carotene, vitamin A, vitamin C, vitamin E, and docosahexaenoic acid. This cross-sectional analysis explored the relationship between the CDAI and ASCVD after adjusting for relevant covariates. Logistic regression models were employed, and subgroup analyses by sex were conducted to discern sex-specific effects. Results: A total of 19,818 individuals were analyzed, with 7.0% of them diagnosed with ASCVD. CDAI distribution and antioxidant analyses revealed higher CDAI levels in non-ASCVD individuals. Standardized antioxidant values increased across CDAI quartiles. Initially, a significant association (odds ratio [95% confidence interval]: 0.96 [0.94–0.99]) was found between the CDAI and ASCVD, which was attenuated after adjusting for covariates (1.0 [0.98–1.02]). Subgroup analyses by sex showed nuanced associations, with the CDAI potentially reducing the risk of ASCVD in men (0.71 [0.53–0.94]) while increasing it in women (1.4 [1.01–1.95]). Conclusions: This study provides valuable insights into the association between dietary antioxidant intake and the risk of ASCVD, highlighting sex-specific differences.