bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Pollinating Fig Wasps’ Entry on Fig Development and the Hormonal Regulation of Sex Differentiation in Ficus hispida
Authors: Guan Yunfang , Zhang Ying , Li Zongbo , Wang Yan , Chen Changqi , Yang Xiaoyan , Gao Jinxia , Miao Baige , Peng Yanqiong , Zhang Yuan
Published: February 2025

Ficus trees (Moraceae) play a vital role in sustaining the stability of tropical and subtropical rainforests. The obligate mutualism between Ficus species and their pollinating fig wasps renders them an exemplary model for investigating insect–plant coevolution. In this study, we employed Ficus hispida Linn. f., an ecologically significant fig species in tropical rainforests, to conduct a wasp-introduction controlled experiment in the field. This method enabled us to precisely delineate the developmental stages of figs. We collected samples at specific intervals and examined the impact of pollinating fig wasp entry on the hormonal metabolism of male and female figs using liquid chromatography–tandem mass spectrometry analysis. The findings demonstrate that pollinator entry significantly decreases fig abscission. Moreover, it substantially altered the developmental indices of the figs. Unpollinated figs exhibit elevated levels of abscisic acid (ABA), which increases the likelihood of fig abortion and reduces the probability of pollinator entry into senescent figs. Following pollinator entry, indole-3-acetic acid (IAA) levels rise in both male and female figs. Male figs show higher concentrations of 1-aminocyclopropane-1-carboxylic acid (ACC), jasmonic acid (JA), and salicylic acid (SA), whereas these changes are less pronounced in female figs. Additionally, pollinated male figs display increased levels of cytokinins (CKs) and other hormones compared to female figs, suggesting a coordinated hormonal response to the stress induced by pollinator oviposition and gall development. Our findings suggest that the entry of pollinators likely triggers the transition from the female to the interfloral phase, with hormonal regulation playing a crucial role in the reproductive dimorphism of figs. This research can offer novel insights into the mechanisms underlying fig–wasp mutualism.
The Effect of Alpine Herbs on the Microbiota of In Vitro Rumen Fermentation
Authors: Andersen Jonas , Massaro Selene , Dallavalle Giulia , Solovyev Pavel , Bontempo Luana , Tagliapietra Franco , Franciosi Elena
Published: February 2025

Milk from cows grazing on alpine pastures has higher quality than milk from indoor-fed cows, likely due to diet-driven differences in rumen microbiota. We assessed the effects of supplementing alpine herbs—each varying in its content of fiber, protein, and polyphenol—on rumen microbiota via in vitro fermentation, comparing these to a grass hay control using metagenomic sequencing. Fermentations with alpine herbs compared to grass hay control had higher content of fibrolytic Prevotella and lower abundances of Butyrivibrio, Ruminococcaceae, Anaerovibrio, Succiniclasticum, and Desulfovibrio. Fermentations with high starch content (Alchemilla vulgaris, Gallium odoratum and Sanguisorba officinalis) had low, microbial diversity, while fermentations with high content of structural fibre (Sisymbrium officinale, Tanacetum vulgare, and Cicerbita alpina) had high microbial diversity. C. alpina, Sa. officinalis, and T. vulgare fermentations that had high lignin content showed a higher abundance of Bacteroidetes and a lower abundance of Firmicutes. Fermentations with high protein content (G. odoratum and T. vulgare) induced higher abundance of fibrolytic Lachnospiraceae. Sa. officinalis and A. vulgaris fermentations with high content of polyphenols were associated with increased abundances of Streptococcus and family RF-16 and lower abundances of family BS11 and Desulfovibrio. Fermentations with C. alpina and Si. Officinale induced higher abundance of fibrolytic Fibrobacter succinogenes. The beta diversity between fermentations corresponded to differences in the contents of protein, lignin, and polyphenols in the plant material. In conclusion, different herbs can promote the abundance of various fibrinolytic bacteria and change the microbial diversity, which has potential to increase the feed efficiency and the robustness of microbiota and reduce methane production.
Correction: Marti et al. Gamification of Orthodontic Treatment with Personalised Facemasks: Enhancing Patient Compliance Through Playful Engagement. Future Internet 2024, 16, 446
Authors: Marti Patrizia , Teverini Giulia , Goracci Cecilia , Franchi Lorenzo
Published: February 2025

In the original publication [...]
Live Aspergillus cristatum from Fuzhuan Brick Tea Alleviates DSS-Induced Colitis by Intestinal Barrier Restoration and Suppressing NLRP3 Signaling Pathway Regulation
Authors: Wang Xin , Cheng Miaomiao , Liu Jinhu , Guo Yaodong , Zhang Yuxiang , Yuan Yahong , Yue Tianli
Published: February 2025

Probiotics are considered an effective strategy for relieving DSS-induced colitis. This study investigated the protective effects and mechanisms of Aspergillus cristatum, a potential probiotic fungus from Fuzhuan brick tea, on colitis. Supplementation with live 102 spores/mL of A. cristatum H-1 and 105 spores/mL of A. cristatum S-6 significantly improved gut integrity by preventing colon shortening, mucus disruption, and goblet cell depletion. Additionally, it significantly reduced proinflammatory cytokines IL-6 and TNF-α levels, enhanced the expression of tight junction molecules (ZO-1, Claudin-1, E-cadherin, and MUC1) and suppressed the NLRP3 signaling pathway. Live A. cristatum H-1 (102 spores/mL) and A. cristatum S-6 (105 spores/mL) can effectively improve colitis. But the inactivated A. cristatum H-1 did not exhibit effective anti-inflammatory effects and significant interspecies differences. In a word, live low-dose A. cristatum H-1 and high-dose A. cristatum S-6 promise a valuable approach to improving colitis. This research not only enhances our understanding of probiotics and their potential therapeutic uses but also sets the stage for future investigations into the mechanisms of action and clinical utilization of A. cristatum in treating colitis and other gut disorders.
Neuromolecular Basis of Impaired Conditioned Taste Aversion Acquisition in Valproate-Induced Rat Model of Autism Spectrum Disorder
Authors: Pal Tapasya , Harvey Savannah , Levine Allen S. , Olszewski Pawel K. , Klockars Anica
Published: February 2025

Background/Objectives: Autism spectrum disorder (ASD), defined by social, behavioral, and cognitive anomalies, is also associated with dysregulated appetite. ASD individuals, often described as “picky eaters”, exhibit restricted dietary preferences and a pronounced avoidance of novel foods. This suggests that the perceived safety of specific tastants may be a crucial determinant of dietary acceptance in ASD. Here, we explore the hypothesis that conditioned taste aversion (CTA), a learned avoidance of foods whose intake promotes sickness, is exacerbated in ASD. Methods: We assessed the magnitude of a lithium chloride (LiCl)-induced CTA in the valproic acid (VPA) rat model of autism versus in healthy control rats. We also examined the effect of a standard 3 mEq LiCl dose on transcript and neuronal activation changes in brain circuits mediating feeding behavior and associative learning. Results: Surprisingly, we found that while 3 mEq LiCl induced CTA in healthy controls, even the 6 mEq dose was ineffective in generating aversion in VPA rats. LiCl at 3 mEq affected c-Fos immunoreactivity in the hypothalamus and amygdala in controls, whereas in VPA rats it did not produce any c-Fos changes. Gene expression analysis of feeding-related genes (AgRP, NPY, OXT) and those involved in regulating stress and anxiety (DOR and MC3R) were differentially regulated in the VPA rats. Interestingly, transcripts for COMT1, AgRP, OXT, and MC3R were downregulated in saline-treated VPA rats compared to saline-treated controls. Conclusions: We conclude that VPA rats show blunted CTA responsiveness, which is reflected by a differential impact of LiCl on circuits that promote the acquisition of CTA in healthy versus autistic individuals.
A Revision of Historical Earthquakes in the Ionian Sea, Greece: Island of Lefkada
Authors: Papadopoulos Gerassimos A. , Triantafyllou Ioanna
Published: February 2025

The central Ionian Sea is one of the most seismogenic areas in the Mediterranean Sea region. In particular, the island of Lefkada, Greece, has experienced many catastrophic earthquakes. The historical seismicity of Lefkada has been revised by utilizing published and little-known macroseismic information sources, e.g., administrative documents, letters, marginal notes, and eyewitness accounts. We organized a new descriptive and parametric catalogue of 44 earthquakes that had their maximum macroseismic intensity in Lefkada and covered the time interval from the 15th century A.D. up to 1911. Earthquake dates, origin times, intensities, magnitudes, and epicentral coordinates were estimated or revised. Magnitudes estimated in previous catalogues in general are larger with respect to our magnitude determinations, possibly due to different calculation methods. The descriptive part of the catalogue includes descriptions of the earthquakes’ impact on buildings and of environmental effects, e.g., landslides and local tsunamis. The catalogue completeness gradually increases with time but is likely complete for the entire period examined lower magnitude threshold Mw = 6.0. One important yet puzzling earthquake is the large one that reportedly ruptured the Strait of Otranto and damaged an unprecedentedly extensive region in Italy, Albania, and Greece, including Lefkada, on 9/20 February 1743. Little-known documents revealed that the heavy destruction supposedly caused in Lefkada was very likely due to amalgamated information regarding local earthquakes and the large one.
Assessing the Relationships of Expenditure and Health Outcomes in Healthcare Systems: A System Design Approach
Authors: Vărzaru Anca Antoaneta
Published: February 2025

Background/Objectives: The COVID-19 pandemic has significantly altered healthcare systems worldwide, highlighting healthcare expenditure’s critical role in fostering population resilience and wellness. This extraordinary situation has brought to light the delicate balance that governments must maintain between the need to protect public health and budgetary restraints. The relationship between healthcare expenditure and outcomes, such as healthy life years, health expectancy, and standardized death rate, has become a central point in understanding the dynamics of healthcare systems and their capacity to adapt to emerging challenges. Methods: Using extensive datasets and predictive approaches such as artificial neural networks, exponential smoothing models, and ARIMA techniques, this study explores these connections in the context of the European Union. Results: The study better explains how healthcare financing schemes influence important health outcomes by examining past trends and forecasting future developments. The results show that household healthcare expenditures correlate negatively with standardized death rates and substantially benefit healthy life years and health expectancy. These findings underline the significance of household contributions in influencing health outcomes across various healthcare systems. Long-term and strategic investments in health services are essential, as the pandemic has demonstrated the proactive capacity of well-designed healthcare systems to reduce risks and enhance overall resilience. The results suggest that focused investments can raise life expectancy and lower death rates, supporting the development of robust, adaptable healthcare systems in the post-pandemic era. Conclusions: The main contribution of this research is demonstrating the significant role of healthcare expenditure, particularly household contributions, in improving key health outcomes and fostering healthcare system resilience in the EU context.
CPPU and Ethylene Inhibitors as an Environmentally Friendly Strategy for Improving Fruit Retention, Yield, and Quality in Avocado
Authors: Abdel-Sattar Mahmoud , Mostafa Laila Y. , Ali Saddam H. , Rihan Hail Z. , Eshra Dalia H.
Published: February 2025

Avocado fruit drop after fruit set causes avocado orchards to suffer significant losses in the fruit yield, oil yield, and quality parameters of fruits. An insufficient crop load, as a result of excessive fruit drop, can reduce avocado orchard profitability. Hence, this study aimed to mitigate these problems using 1-methylcyclopropene (1-MCP), aminoethoxyvinylglycine (AVG), and N-(2-Chloro-4-pyridyl)-N′-phenyl urea (CPPU) as an environmentally friendly and cost-effective strategy to reduce accumulative fruit drop and enhance the productivity and quality of Fuerte avocado fruits. The experiment was conducted over two consecutive seasons using a randomized complete block design with eight treatments: control, 1-MCP (200 ppm), AVG (200 ppm), CPPU (5 ppm), 1-MCP + AVG, 1-MCP + CPPU, AVG + CPPU, and 1-MCP + AVG + CPPU. These treatments were applied twice, at full bloom and at the beginning of the fruit set. Avocado trees treated with 5 ppm CPPU significantly reduced accumulative fruit drop. Additionally, treatments with 1-MCP + AVG + CPPU and CPPU at 5 ppm notably improved the yield and quality of Fuerte avocado fruits by increasing fruit weight, length, width, dry matter content, total carbohydrates, crude protein, total soluble solids (TSSs), and fruit mineral content (P, K, Ca, Mg, and Fe). In contrast, treatments with 1-MCP or/and AVG had a negative impact on fruit TSSs, acidity, and carotenoid content, while producing the highest levels of chlorophyll a, b, and total chlorophyll. Treatments with CPPU alone or combined with 1-MCP and/or AVG significantly enhanced avocado oil content, with slight effects on peroxide, iodine, and saponification values. Based on the results, 1-MCP + AVG + CPPU treatment is recommended for avocado growers to enhance fruit growth, yield, quality, and oil production.
Comparing Barriers and Facilitators to Physical ActivityAmong Underrepresented Minorities: Preliminary Outcomes from a Mixed-Methods Study
Authors: Alamilla Rafael A. , Kaushal Navin , Bigatti Silvia M. , Keith NiCole R.
Published: February 2025

Physical activity (PA)’s benefits are well established, yet many U.S. adults fail to meet PA guidelines. This is especially true for minorities facing social inequities. This study explored PA’s barriers and facilitators among urban Midwestern minorities using a mixed-methods approach framed on the socio-ecological model. A cross-sectional survey was conducted between January and June 2024 among community-dwelling minorities. Participants were grouped as completing low (LLPA) or high (HLPA) weekly leisure-time PA for comparison. Quantitative analysis included MANOVA, follow-up ANOVAs, and calculation of effect sizes. Qualitative data were assessed using inductive thematic analysis. Twenty-nine adults (44.83% Black, 41.37% Latino) participated in the study. The HLPA group (n = 18) reported higher leisure-time PA (p = 0.001, d = 2.21) and total PA (p = 0.02, d = 1.00) compared to the LLPA group (n = 11). LLPA participants faced more personal barriers to PA (p = 0.02, d = −0.92). Common barriers identified in the interviews included a lack of time and financial costs. Facilitators included social support and available PA facilities. Both groups achieved the USPA guidelines through different PA domains. Increasing social support and lowering PA-related costs could enhance participation. Addressing barriers and leveraging existing facilitators are crucial to increasing PA among minorities.
Overall Observed Survival of Female Breast, Cervical, Colorectal, and Prostate Cancers in Antigua and Barbuda, 2017–2021: Retrospective Data from Four Study Sites
Authors: Bovell Andre A. N. , Rhudd Adrian , Ncayiyana Jabulani , Ginindza Themba G.
Published: February 2025

Understanding cancer survival is important for countries such as Antigua and Barbuda, where female breast, cervical, colorectal, and prostate cancers are burdensome to the healthcare system. This study therefore aimed to estimate the survival probabilities of patients diagnosed with these cancers between 2017 and 2021. A retrospective analytical study design was used to evaluate cancer cases abstracted from medical records at key study sites. Estimates of observed survival probabilities were determined using a Kaplan–Meier analysis. Significant differences between survival curves were assessed using the log-rank test. Hazard ratios were calculated using Cox regression. A p-value < 0.05 indicated significance. A total of 391 diagnosed cases were included in this study (2017–2021): female breast cancer accounted for 42%, cervical cancer accounted for 10%, colorectal cancer accounted for 20%, and prostate cancer accounted for 28%. Overall, the mean age of the participants was 61.5 (±12.9) years; 62% were female, 73% were aged > 55 years, 56% were from St. John’s, and 82% were alive at the end of 2021. The median overall survival (years) was 4.8 for female breast cancer, 4.1 for cervical cancer, 4.5 for colorectal cancer, and not reached for prostate cancer. The cancer-specific overall observed 5-year survival probabilities were 44.9% for female breast cancer, 10.8% for cervical cancer, 19.6% for colorectal cancer, and 69.0% for prostate cancer. Significant associations between disease stage and overall survival were observed in female breast and colorectal cancers. This study provides important evidence for the 5-year observed survival probabilities of the studied cancers. Healthcare improvements that support cancer survival are required.
Adsorption of Serum Fetuin onto Octacalcium Phosphate and Its Relation to Osteogenic Property
Authors: Tsuboi Yuki , Hamai Ryo , Okuyama Kyosuke , Tsuchiya Kaori , Shiwaku Yukari , Yamauchi Kensuke , Suzuki Osamu
Published: February 2025

This study aimed to investigate how the chemical elements in relation to octacalcium phosphate (OCP) hydrolysis affect the osteoblastic differentiation in the presence of serum fetuin. The adsorption of fetuin onto OCP was examined in buffers having different degrees of supersaturation (DS) with respect to OCP and hydroxyapatite (HA) at pH 7.4 and 37 °C. The osteoblastic differentiation of mesenchymal stem cells (MSCs) was evaluated in cultures with OCP and 0 to 0.8 mg/mL of fetuin. The amount of fetuin adsorbed increased with increasing DS in the buffer. In the MSC culture, the coexistence of OCP and 0.2–0.4 mg/mL of fetuin close to serum level increased alkaline phosphatase activity; however, the activity was suppressed by 0.2–0.8 mg/mL of fetuin. Transmission electron microscopy revealed de novo crystal formation on OCP in supersaturated buffer and culture media with respect to OCP and HA at lower fetuin concentrations. Infrared spectroscopy and DS estimation indicate that the hydrolysis of OCP with de novo apatite formation was promoted in the culture media at 0.2–0.4 mg/mL of fetuin. These results suggest that OCP may promote osteoblastic differentiation if the suitable conditions are attained regarding the chemical elements and fetuin adsorption around OCP.
Transcriptome and MicroRNA Analysis of Juglans regia in Response to Low-Temperature Stress
Authors: Zhao Haochang , Luo Xia , Guo Caihua , Zhang Zhongrong , Ma Kai , Niu Jianxin , Quan Shaowen
Published: February 2025

Walnuts are among the globally significant woody food and oil tree species. At high latitudes, they frequently experience late-frost damage, inducing low-temperature stress, which significantly affects walnut seedlings. The aim of this study was to investigate the physiological and biochemical alterations in walnut seedlings under low-temperature (LT) stress along with its underlying molecular mechanisms. Physiological indices were determined, and the transcriptome and miRNA were sequenced by sampling leaves (0 h, 6 h, 12 h, 24 h, and 48 h) of two-month-old live seedlings of walnuts treated with a low temperature of 4 °C. The results indicated that LT stress induced an increase in electrical conductivity and malondialdehyde content while simultaneously causing a reduction in Fv/Fm. From the transcriptome comparison between the control and treated groups, a total of 12,566 differentially expressed genes (DEGs) were identified, consisting of 6829 up-regulated and 5737 down-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the DEGs were primarily enriched in polysaccharide metabolic processes, responses to abscisic acid and phenylpropanoid biosynthesis pathways. Furthermore, the miRNA database identified 1052 miRNAs in response to low-temperature stress in walnuts; these miRNAs were found to target 7043 predicted genes. Through the integration and analysis of transcriptome and miRNA data, 244 differential DEGs were identified. Following GO and KEGG enrichment analyses of the differential target genes, we identified that these genes primarily regulate pathways involved in starch and sucrose metabolism, glyoxylate and dicarboxylate metabolism, and glycerophospholipid biosynthesis, as well as phenylalanine, tyrosine, and tryptophan biosynthesis, in walnut leaves under LT stress. Additionally, we conducted an in-depth analysis of the associations between differentially expressed genes (DEGs) and differentially expressed microRNAs (DEMs) within the starch and sucrose metabolism pathway. Real-time fluorescent quantitative PCR (qRT-PCR) validation of the expression patterns of a subset of differential genes confirmed the accuracy of the transcriptome data. This study unveils the potential molecular mechanisms underlying walnut’s response to low-temperature stress, providing valuable genetic resources for future research on the cold tolerance mechanisms of walnut in response to late-frost damage.
Network Pharmacology Analysis and Experimental Validation of Tectoridin in the Treatment of Ischemic Stroke by Inhibiting Apoptosis and Regulating Inflammation
Authors: Lu Tingting , Feng Zhen , Xue Huiming , Jin Chang , Zhang Yue , Ai Yongxing , Zheng Meizhu , Shi Dongfang , Song Kai
Published: February 2025

The flowers of Pueraria lobate (Puerariae Flos) have served as a traditional Chinese medicinal and food herbage plant for many years. Tectoridin is one of the most active metabolites extracted from flowers of Pueraria lobate and has a variety of beneficial activities, including antioxidative, hypoglycemic, and anti-inflammatory activities. Nevertheless, the functions and potential mechanisms underlying tectoridin in cerebral ischemia/reperfusion injury have not been well interpreted; thus, a network analysis strategy was performed to systematically evaluate its pharmacological mechanisms, which were further validated in rats with cerebral ischemia. Network analysis predicted that tectoridin could attenuate brain damage after stroke by modulating signaling pathways associated with redox, inflammation, and autophagy. The experimental results demonstrated an improvement in neurological function in rats treated with tectoridin, along with a significant reduction in cerebral infarction volume. The neuroprotective benefits of tectoridin stem, in part, from its antioxidant capabilities, which include the upregulation of Nrf2/HO-1 protein expression, reduction of the TLR4/MYD88/NF-κB inflammatory pathway, and inhibition of the PI3K/Akt/mTOR pathway, contributing to its anti-apoptotic effects. This investigation offers a thorough examination of the pathways and targets linked to the therapeutic effects of tectoridin on ischemic stroke, highlighting its anti-inflammatory, antioxidative, and anti-apoptotic mechanisms. These findings serve as a valuable reference for the development and exploration of effective anti-ischemic stroke medications.
Enhancing UAV Security Against GPS Spoofing Attacks Through a Genetic Algorithm-Driven Deep Learning Framework
Authors: Al-Sabbagh Abdallah , El-Bokhary Aya , El-Koussa Sana , Jaber Abdulrahman , Elkhodr Mahmoud
Published: February 2025

Unmanned Aerial Vehicles (UAVs) are increasingly employed across various domains, including communication, military, and delivery operations. Their reliance on the Global Positioning System (GPS) renders them vulnerable to GPS spoofing attacks, in which adversaries transmit false signals to manipulate UAVs’ navigation, potentially leading to severe security risks. This paper presents an enhanced integration of Long Short-Term Memory (LSTM) networks with a Genetic Algorithm (GA) for GPS spoofing detection. Although GA–neural network combinations have existed for decades, our method expands the GA’s search space to optimize a wider range of hyperparameters, thereby improving adaptability in dynamic operational scenarios. The framework is evaluated using a real-world GPS spoofing dataset that includes authentic and malicious signals under multiple attack conditions. While we discuss strategies for mitigating CPU resource demands and computational overhead, we acknowledge that direct measurements of energy consumption or inference latency are not included in the present work. Experimental results show that the proposed LSTM–GA approach achieved a notable increase in classification accuracy (from 88.42% to 93.12%) and the F1 score (from 87.63% to 93.39%). These findings highlight the system’s potential to strengthen UAV security against GPS spoofing attacks, provided that hardware constraints and other limitations are carefully managed in real deployments.
Laryngeal Electromyography as a Predictive Factor in the Evolution of Unilateral Recurrent Paralysis Post-Thyroidectomy
Authors: Tarabichi Shirley , Sarafoleanu Codrut
Published: February 2025

Background: Dysphonia, a common symptom after thyroid surgery, is most often caused by damage to the recurrent laryngeal nerve. Laryngeal electromyography (LEMG) is used as a qualitative diagnostic tool to distinguish neurological etiology from other causes of dysphonia. The purpose of this study is to establish the value of LEMG as a predictor factor in the recovery of unilateral recurrent paralysis post-thyroidectomy. Methods: This study included 11 patients with unilateral vocal fold palsy (UVFP) evidenced on the videostrobolaryngoscopy (VSL) after thyroidectomy. Electrical activity of thyroarytenoid (TA) muscles of the patients included in the study was recorded through LEMG and the prognosis of the lesions was classified as excellent, fair, or poor based on the presence of spontaneous activity and motor unit recruitment. Results: LEMG at the first clinic visit showed an excellent prognosis in three of the cases, a fair prognosis in three of the cases, and five of them indicated a poor prognosis. At 6 months after the first LEMG, patients with a poor prognosis were unchanged and showed no LEMG improvement. Those with an excellent prognosis showed an increased recruitment response, and LEMG was normal. In one patient with a fair prognosis and minimal spontaneous activity, LEMG recruitment decreased during reevaluation. The other two fair-prognosis patients had a normal LEMG. Conclusions: A correlation was found between LEMG findings and functional recovery of the vocal cords, demonstrating that the presence of spontaneous activity represents a negative prognostic factor. However, due to limited patient cohorts, the sensitivity of the LEMG as a prognostic tool in the functional recovery of the larynx is not yet established and requires further research.
The Diagnostic Yield of Implantable Loop Recorders Stratified by Indication: A “Real-World” Single-Center Experience
Authors: Pistelli Lorenzo , Di Cori Andrea , Parollo Matteo , Torre Marco , Fiorentini Federico , Barletta Valentina , Giannotti Santoro Mario , Grifoni Gino , Canu Antonio , Segreti Luca , De Lucia Raffaele , Viani Stefano , Zucchelli Giulio
Published: February 2025

Background/Objectives: Implantable loop recorders (ILRs) are widely used for the diagnosis of unexplained syncope, palpitations, and cryptogenic stroke. While ILRs demonstrate clinical utility, data on their diagnostic yield and value in real-world settings remain limited. This study evaluates ILR performance, diagnostic yield, and clinical impact across multiple indications. Methods: We retrospectively analyzed 316 patients who underwent ILR implantation between 2017 and 2023 at a single center. Indications included unexplained syncope, palpitations, and atrial fibrillation (AF) detection. Diagnostic yield, defined as the ratio of positive diagnoses to implants, and diagnostic value, defined as diagnoses leading to therapeutic changes, were assessed. Diagnostic appropriateness, reflecting diagnoses consistent with implant indications, was also investigated. Continuous variables were analyzed using an independent samples t-test or ANOVA, when appropriate; dichotomous variables were analyzed using a chi-square test. Results: The overall diagnostic yield was 30%, with most diagnoses occurring within 24 months post-implantation. Bradyarrhythmias were diagnosed earlier (mean: 290 days) than tachyarrhythmias (590 days, p = 0.04). The diagnostic value was 29%, and the appropriateness reached 70%. The diagnostic-value-to-diagnostic-yield ratio was shown to be as high as 97%, suggesting that whenever a diagnosis was made, it was of clinical impact. Patients with presyncope showed a higher diagnostic yield, particularly for tachyarrhythmias. Device re-implantation showed limited utility, as only one diagnosis (classified as bystander) was achieved in 32 re-implanted patients. After 900 days, the diagnostic yield decreased significantly, with the number needed to follow (NNF) rising from 3.85 to 18 (p < 0.001). Conclusions: ILRs are effective for arrhythmia detection, demonstrating significant diagnostic and therapeutic impact, particularly within the first two years. The recurrence of presyncope and atrial dilation was associated with higher yields, while isolated syncope posed diagnostic challenges. Prolonged monitoring beyond 900 days and device re-implantation provided diminishing returns.
Real-World Lessons with Fremanezumab as the Third Available CGRP Monoclonal Antibody in a Third-Level Hospital: Focus on the Factors Predicting Response
Authors: Polanco Marcos , Gárate Gabriel , Sánchez-Gudín Julia , Madera Jorge , Pascual Julio , González-Quintanilla Vicente
Published: February 2025

Background: Fremanezumab was the third CGRP antibody available in our hospital. This examination of our experience with fremanezumab is focused on identifying the predictors of response. Methods: This was a prospective observational study in which we included high-frequency episodic/chronic migraine (HF/CM) patients who were prescribed fremanezumab during the year 2023. Our research involved collecting data on their demographic details, diagnoses made, treatments received, prophylactic measures taken in the past, and any comorbid conditions present. The number of headaches was documented for one quarter prior to and after the initiation of fremanezumab. Results: Eighty-nine patients received fremanezumab (86.5% female, 45.8 ± 12.5 years old, 70.1% naive). The headache days decreased from 21.1 ± 7.6 to 12.4 ± 11.2 days during the initial three months of the treatment, and a total of 55 patients (61.8%) exhibited a response rate of ≥50%. Six out of ten patients refractory to erenumab for at least 6 months responded to fremanezumab. Totals of 17 and 26 patients had been treated at least with galcanezumab or erenumab. The elements influencing non-response were as follows: prior failure to respond to both erenumab and galcanezumab (p < 0.0001), HF/CM length (11.9 ± 7.1 years in non-responders vs. 5.8 ± 4.8 in responders; p < 0.001), the presence of fibromyalgia (p < 0.001), anxiety–depression (p < 0.001), an almost daily headache baseline (>28 days/month) (p < 0.0001), and analgesic overuse (p < 0.0001). The response rate was unaffected by age and experience. After a multivariate logistic analysis, almost daily headaches (p < 0.001), a length of HF/CM > 6 years (p = 0.015), and anxiety–depression (p = 0.017) remained significant. Fremanezumab showed excellent tolerance. Conclusions: These real-life results confirm the efficacy of fremanezumab. The main factors associated with a lack of response were almost daily/daily headaches and a disease duration > 6 years. Half of the patients who failed to respond to erenumab improved on fremanezumab, making it sensible to switch to a treatment with a different mechanism of action, but trying a third anti-CGRP treatment in patients with no response to both a receptor-targeted and a ligand-targeted CGRP antibody hardly seems justifiable from our experience.
Natural Course and Long-Term Outcomes of Gastric Subepithelial Lesions: A Systematic Review
Authors: Iwamuro Masaya , Okada Hiroyuki , Otsuka Motoyuki
Published: February 2025

Background/Objectives: Gastric subepithelial lesions (SELs) are often incidentally detected during endoscopic examinations, with most patients being asymptomatic and lesions measuring <20 mm. Despite their generally indolent nature, certain SELs, such as gastrointestinal stromal tumors, require resection. Current guidelines recommend periodic surveillance; however, the natural course and long-term outcomes of gastric SELs have not been sufficiently investigated. This systematic review aimed to synthesize evidence on the progression, growth rate, and risk factors associated with gastric SELs to inform clinical management strategies. Methods: A comprehensive search of PubMed was conducted for peer-reviewed studies published between January 2000 and November 2024. Eligible studies included original studies on the follow-up and progression of gastric SELs. Non-English articles, reviews, case reports, and unrelated topics were excluded. In total, 277 articles were screened, with 15 additional articles identified through manual screening. Ultimately, 41 articles were included in the analysis. The study protocol is registered in PROSPERO (CRD42024614865). Results: Large-scale studies reported low growth rates of 2.0–8.5% over 2.0–5.0 years, while smaller studies reported a broader range of growth rates of 5.4–28.4%. The factors contributing to these discrepancies include patient selection, follow-up duration, and growth criteria. Risk factors for lesion size increase include larger initial lesion size, irregular margins, heterogeneous echo patterns, and certain tumor locations. Conclusions: These findings underscore the need for individualized management strategies based on lesion size, imaging characteristics, and risk factors. The close monitoring of high-risk lesions is crucial for timely intervention. Standardized growth criteria and optimized follow-up protocols are essential for improving clinical decision making and patient outcomes.
Analysis of Postoperative Outcomes in Unilateral Versus Bilateral DIEP Flap Reconstructions: A Single-Center Retrospective Study
Authors: Tekdogan Boran , Martineau Jérôme , Verbat Miroslava , Dong Edward T. C. , Correia Daniel , Oranges Carlo M.
Published: February 2025

Background/Objectives: The DIEP flap is among the preferred techniques in autologous breast reconstruction due to better long-term outcomes, including higher satisfaction and more natural breast shape compared to implant-based breast reconstruction. With the rise in genetic testing, bilateral DIEP reconstructions are becoming more common, though they carry a higher risk of complications. This study aims to compare the risks between unilateral and bilateral procedures to improve surgical decision-making. Methods: A retrospective, single-center review was conducted on female patients who underwent DIEP flap breast reconstruction between January 2018 and May 2024. The study included patients with complete medical records and follow-up data, excluding those with incomplete records. Patient characteristics, operative details, and complications were thoroughly analyzed, with donor site complications assessed per patient and recipient site complications per breast. Results: During the study, 141 DIEP flaps were performed on 114 women, with 87 unilateral and 27 bilateral reconstructions. Age and BMI were similar between groups. However, chemotherapy was more common in the bilateral group (85% vs. 47%, p = 0.0011). Operative time was significantly longer in bilateral procedures (650 vs. 460 min, p < 0.0001). There were no statistically significant differences in recipient and donor site complications across groups. The hospital stay was significantly longer in the bilateral group (11 vs. 8.8 days, p = 0.024). Conclusions: Bilateral and unilateral DIEP flap breast reconstructions have similar complication and early take-back rates.
Systematic Review of Clinical Outcome Parameters of Conservative Treatment of Adolescent Idiopathic Scoliosis Patients
Authors: Kuru Çolak Tuğba , Durmuş Betül Beyza , Saatçı Ece Zeynep , Çağlar Engin , Akçay Burçin , Maeso Santiago Lasa
Published: February 2025

Background: The purpose of this systematic review was to investigate the clinical outcome measures, either in separation or in conjunction with the Cobb angle, that were employed in randomized controlled trials to evaluate posture and spinal deformity. Methods: The PubMed, PEDro, OVID, and Scopus electronic databases were used to search for published articles from January 2004 to May 2024. All the searches included English language studies. Keywords were determined as “scoliosis, exercise, physical activity, brace, bracing, conservative treatment, rehabilitation, physiotherapy and physical therapy”. Results: The most commonly used clinical evaluation parameters other than the Cobb angle in the studies were the ATR and surface topography measurements. The most commonly used assessment methods were POTSI asymmetry assessment performed with measurements made on photographs, the WRVAS, a deformity perception assessment evaluated with different photographs, and the SRS-22 scale, a disease-specific quality of life assessment. Conclusions: New developments in the treatment of scoliosis have brought about alternative measurement techniques that offer a more comprehensive view of patient outcomes. As a result of the review of the literature, it has emerged that radiation-free, valid, and reliable multidimensional evaluations should be performed in follow-up and treatment efficacy evaluations after initial diagnosis in adolescent idiopathic scoliosis.
Extreme Preterm Delivery Between 24+0 and 27+6 Weeks: Factors Affecting Perinatal Outcome
Authors: Kowalczyk-Buss Joanna , Demertzidou Eleftheria , El-Toukhy Sara , Ramadan Ghada , Akolekar Ranjit
Published: February 2025

Objectives: The aim of this study was to investigate the factors associated with the prediction of perinatal survival in pregnancies with extreme preterm delivery between 24+0 and 27+6 weeks’ gestation. Methods: This screening cohort study was undertaken at a large tertiary obstetric and neonatal unit in the United Kingdom. We included singleton pregnancies that booked and delivered at our hospital. Logistic regression analysis was carried out to determine risks of complications in pregnancies delivering preterm after adjusting for maternal and pregnancy characteristics. Effect sizes were expressed as absolute risks (ARs) and odds ratios (ORs) (95% confidence intervals [CI]). Results: The study population included 53,649 singleton pregnancies, including 139 (0.3%) with preterm delivery between 24+0 and 27+6 weeks and 47,006 (99.7%) with term delivery ≥37 weeks. Multivariate regression analysis demonstrated that there was a significant contribution of uterine artery pulsatility index (UtA-PI) and cervical length, but not of maternal factors, in the prediction of preterm delivery <28 weeks. The risk of neonatal death and intact neurological survival in pregnancies delivering <28 weeks was 11.5% and 79.1%, respectively. Caesarean compared to vaginal delivery and female compared to male neonates were associated with a lower incidence of neurological morbidity (6.1% vs. 19.3%; p = 0.016 and 13.1% vs. 26.9%; p = 0.036, respectively). In the prediction of intact perinatal survival, the only significant variable was gestational age at delivery, with survival rates of about 50%, 65%, 80% and 90% at 24, 25, 26 and 27 weeks, respectively. Conclusions: In pregnancies with extreme preterm delivery between 24+0 and 27+6 weeks, caesarean compared to vaginal delivery and female compared to male neonates are associated with a lower incidence of neurological morbidity. The only significant factor in the prediction of intact perinatal survival is gestational age at delivery.
Polyamine Inhibition with DFMO: Shifting the Paradigm in Neuroblastoma Therapy
Authors: Schramm Joseph , Sholler Chloe , Menachery Leah , Vazquez Laura , Saulnier Sholler Giselle
Published: February 2025

Neuroblastoma is a common childhood malignancy, and high-risk presentations, including an MYCN amplified status, continue to result in poor survival. Difluoromethylornithine (DFMO) is a new and well-tolerated treatment for high-risk neuroblastoma. This review article discusses preclinical and clinical data that resulted in the establishment of DFMO as a treatment for neuroblastoma. The review of preclinical data includes a summary of the contribution of polyamine synthetic pathways to high-risk neuroblastoma, the effect that MYCN has on polyamine synthetic pathways, and the proposed mechanism by which DFMO inhibits tumorigenesis. This understanding has led to the discussion of various preclinical combination therapies that may result in a synergistic therapeutic response for high-risk neuroblastoma. We review the clinical trials that show the successful treatment of high-risk neuroblastoma with DFMO, including comparative analysis and traditional neuroblastoma trials using propensity score matching. We review the regulatory path by which DFMO gained approval from the Federal Drug Administration for use as a maintenance therapy following the traditional high-risk neuroblastoma therapy. Finally, we discuss the role of DFMO in future clinical research for neuroblastoma and additional pediatric cancers.
Next-Generation Biomaterials for Wound Healing: Development and Evaluation of Collagen Scaffolds Functionalized with a Heparan Sulfate Mimic and Fibroblast Growth Factor 2
Authors: Gansevoort Merel , Wentholt Sabine , Li Vecchi Gaia , de Vries Marjolein , Versteeg Elly M. M. , Boekema Bouke K. H. L. , Choppin Agnes , Barritault Denis , Chiappini Franck , van Kuppevelt Toin H. , Daamen Willeke F.
Published: February 2025

Fibrosis after full-thickness wound healing—especially after severe burn wounds—remains a clinically relevant problem. Biomaterials that mimic the lost dermal extracellular matrix have shown promise but cannot completely prevent scar formation. We present a novel approach where porous type I collagen scaffolds were covalently functionalized with ReGeneRating Agent (RGTA®) OTR4120. RGTA® is a glycanase-resistant heparan sulfate mimetic that promotes regeneration when applied topically to chronic wounds. OTR4120 is able to capture fibroblast growth factor 2 (FGF-2), a heparan/heparin-binding growth factor that inhibits the activity of fibrosis-driving myofibroblasts. Scaffolds with various concentrations and distributions of OTR4120 were produced. When loaded with FGF-2, collagen–OTR4120 scaffolds demonstrated sustained release of FGF-2 compared to collagen–heparin scaffolds. Their anti-fibrotic potential was investigated in vitro by seeding primary human dermal fibroblasts on the scaffolds followed by stimulation with transforming growth factor β1 (TGF-β1) to induce myofibroblast differentiation. Collagen–OTR4120(-FGF-2) scaffolds diminished the gene expression levels of several myofibroblast markers. In absence of FGF-2 the collagen–OTR4120 scaffolds displayed an inherent anti-fibrotic effect, as the expression of two fibrotic markers (TGF-β1 and type I collagen) was diminished. This work highlights the potential of collagen–OTR4120 scaffolds as biomaterials to improve skin wound healing.
We Need to Talk About Lung Ultrasound Score: Prediction of Intensive Care Unit Admission with Machine Learning
Authors: Oliveira-Saraiva Duarte , Leote João , Gonzalez Filipe André , Garcia Nuno Cruz , Ferreira Hugo Alexandre
Published: February 2025

The admission of COVID-19 patients to the Intensive Care Unit (ICU) is largely dependent on illness severity, yet no standard criteria exist for this decision. Here, lung ultrasound (LU) data, blood gas analysis (BGA), and clinical parameters from venous blood tests (VBTs) were used, along with machine-learning (ML) models to predict the need for ICU admission. Data from fifty-one COVID-19 patients, including ICU admission status, were collected. The information from LU was gathered through the identification of LU findings (LUFs): B-lines, irregular pleura, subpleural, and lobar consolidations. LU scores (LUSs) were computed by summing predefined weights assigned to each LUF, as reported in previous studies. In addition, individual LUFs were analyzed without calculating a total LUS. Support vector machine models were built, combining the available clinical data to predict ICU admissions. The application of ML models to individual LUFs outperformed standard LUS approaches reported in previous studies. Moreover, combining LU data with results from other medical exams improved the area under the receiver operating characteristic curve (AUC). The model with the best overall performance used variables from all three exams (BGA, LU, VBT), achieving an AUC of 95.5%. Overall, the results demonstrate the significant role of ML models in improving the prediction of ICU admission. Additionally, applying ML specifically to LUFs provided better results compared to traditional approaches that rely on traditional LUSs. The results of this paper are deployed on a web app.
Using Machine Learning and Generative Intelligence in Book Cover Development
Authors: Kulishova Nonna , Sajek Daiva
Published: February 2025

The rapid development of machine learning and artificial intelligence approaches is finding ever wider application in various areas of life. This paper considers the problem of improving editorial and publishing processes, namely self-publishing, when designing book covers using machine learning and generative artificial intelligence (GAI) methods. When choosing a book, readers often have certain expectations regarding the design of the publication, including the color of the cover. These expectations can be called color preferences, and they can depend on the genre of the book, its target audience, and even personal associations. Cultural context can also influence color choice, as certain colors can symbolize different emotions or moods in different cultures. Cluster analysis of book cover images of the same genre allows us to identify color preferences inherent in the genre, which is proposed to be used when designing new covers. The capabilities of generative services for creating and improving cover designs are also investigated. An improved flow chart for using GAI in creating book covers in the process of self-publishing is proposed, which includes new stages, namely exploring, conditioning, and evolving. At these stages, the designer creates prompts for GAI and examines how they and GAI’s issuances correspond to the task. Conditioning allows for even more precise adjustment of prompts to features of each book, and the evolving stage also includes post-processing of results already received from GAI. Post-processing, in turn, can be performed both in generative services and by a designer. The experiment allowed us to use the machine-learning method to determine which colors are most often found in book cover layouts of one of the genres and to check whether these colors correspond to harmonious color palettes. In accordance with the proposed scheme of the design process using generative artificial intelligence, versions of book cover layouts of a given genre were obtained.