bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacogenetics of opioid medications for relief of labor pain and post-cesarean pain: a systematic review and meta-analysis
Authors: Giacon Martina , Cargnin Sarah , Talmon Maria , Terrazzino Salvatore
Published: January 2025

Objective

Several studies have attempted to identify genetic determinants of clinical response to opioids administered during labor or after cesarean section. However, their results were often contrasting. A systematic review and meta-analysis was conducted to quantitatively assess the association between gene polymorphisms and clinical outcomes of opioid administration in the treatment of labor pain and post-cesarean pain.

Methods

A comprehensive search was performed up to December 2023 using PubMed, Web of Knowledge, Cochrane Library, and OpenGrey databases. The clinical endpoints of interest were pain score after opioid treatment, total opioid consumption, patient’s analgesic satisfaction, and incidence of opioid side effects. Random-effects meta-analyses were conducted when data were available in at least three studies.

Results

Twenty-six studies enrolling 7765 patients were included in the systematic review. Overall, a total of 12 candidate polymorphic genes (OPRM1, COMT, CYP2D6, CYP3A4, ABCB1, ABCC3, UGT2B7, CGRP, OPRK1, OPRD1, KCNJ6, KCNJ9) were considered by the included studies, among which the most investigated variant was OPRM1 rs1799971. Overall pooled results indicated that individuals carrying the G allele of OPRM1 rs1799971 required higher opioid doses for pain management in comparison to rs1799971 AA subjects (standardized mean difference: 0.26; 95% CI: 0.09–0.44; P = 0.003). Such an association was confirmed in the subgroups of patients with labor pain and post-cesarean pain.

Conclusion

The present meta-analysis provides strong evidence of an association between OPRM1 rs1799971 and opioid dose requirement for relief of labor pain or post-cesarean pain. However, given the insufficient evidence for other polymorphic gene variants, large studies are still needed to investigate the impact of genetic variability on the efficacy and safety of opioid medications for relief of labor pain and post-cesarean pain (INPLASY Registration No. 202410040).
The Amphibian Major Histocompatibility Complex—A Review and Future Outlook
Authors: Sabino-Pinto Joana , Maan Martine E.
Published: January 2025

The major histocompatibility complex (MHC) is a cluster of functionally related genes encoding proteins which, among other functions, mediate immune system activation. While the MHC of many vertebrates has been extensively studied, less is known about the amphibian MHC. This represents an important knowledge gap because amphibians mark the evolutionary transition from an aquatic to a terrestrial lifestyle and often maintain a biphasic lifestyle. Hence, they tend to be exposed to both aquatic and terrestrial pathogen communities, providing opportunities to gain fundamental insights into how the immune system responds to different environmental challenges. Moreover, amphibians are globally threatened by invasive pathogens and the MHC may play a role in combating population decline. In this review, we summarize the current state of knowledge regarding the amphibian MHC and identify the major differences with other vertebrates. We also review how the number of MHC gene copies varies across amphibian groups and how MHC-based variation relates to amphibian ontogeny, behaviour, disease, and phylogeography. We conclude by identifying knowledge gaps and proposing priorities for future research.
Anxiety of microbially synthesized Fe3O4-SPIONs on embryonic/larval ontogeny in red tilapia (Oreochromis sp.)
Authors: Abouelkheir Samia S. , Mourad Mona M.
Published: January 2025

Iron oxide nanoparticles, recognized for their superparamagnetic properties, are promising for future healthcare therapies. However, their extensive use in medicine and electronics contributes to their discharge into our environments, highlighting the need for further research on their cellular damage effects on aquatic organisms. While the detrimental properties of other compounds have been stated in the early-life stages of fish, the cytotoxic consequences of superparamagnetic iron oxide nanoparticles (SPIONs) in these stages are still unexplored. Therefore, using the red tilapia (Oreochromis sp.) as a model organism, this study is the first to talk about the subtle cellular alterations caused by biologically induced biomineralized Fe3O4-SPIONs by Bacillus sp. in the early-life stages. Once the red tilapia eggs were fertilized, they were challenged to different doses of SPIONs (0, 5, 10, 15, and 30 mg/l), and their tenfold increases (50, 100, 150, and 300 mg/l) for 72 h. The hatching rate, malformation rate, body length, and deformities of the larvae were all studied. Our research showed that iron oxide nanoparticles were harmful to the early stages of life in red tilapia embryos and larvae. They slowed hatching delay, a decrease in survival rate, an increase in heart rate, bleeding, arrested development, and membrane damage and changed the axis’s physiological structure. Additionally, results indicated numerous deformities of red tilapia larvae, with lordosis, kyphosis, and scoliosis once subjected to 50 and 150 mg/l of SPIONs concentrations, respectively. This study could assist us in recognizing the risk and evaluating the disrupting potential of nanoparticles. The key objective of this inquiry is to describe the existing features of the produced magnetite SPIONs (29.44 g/l) including their morphological, chemical, and magnetic characteristics. Illustrate their current role in medicinal applications and aquatic organisms by studying in vivo cytotoxic effects to motivate the development of enhanced SPIONs systems. As a recommendation, more research is needed to completely understand how various exposure endpoints of SPIONs disturb the bodies of red tilapia in the early stages.

Key points

• Biogenic SPIONs: a material of the future.

• Characterization is essential to assess the functional properties of the produced SPIONs.

• Fe3O4-SPIONs’ impact on the red tilapia ontogeny.

Graphical abstract
Can mindfulness have long-term impact on patients with fibromyalgia? A two-year prospective follow-up study of a mindfulness-based intervention
Authors: Zangi Heidi A. , Haugmark Trond , Provan Sella Aarrestad
Published: January 2025

To examine changes in symptoms and health status in patients with fibromyalgia (FM) 24 months after participating in the mindfulness-based group-program, the Vitality Training (VTP), followed by physical exercise counselling. Seventy-six participants, mean age (range) 43 (26–52), females 69 (91%), diagnosed with FM according to the ACR 2011-criteria received the VTP in a previous randomised controlled trial. Control group participants could receive the VTP after a 12-month observation period, therefore only data from the intervention group were analysed in the present study. Self-reported data were collected electronically at baseline, 3, 12 and 24 months. Outcomes were patient global impression of change (PGIC), FM-severity, i.e. widespread pain (WPI) and symptom severity (SSS), pain, fatigue, sleep quality, psychological distress, motivation and barriers for physical activity, mindfulness and work participation. Trends across time-points were analysed using mixed models for repeated measurements. At 24-months, 48 (56.5%) participants responded, 94% female, median (range) age 46 (28–54), symptom duration 12 (5–33) years. Seven participants reported much/very much better on the PGIC; 21 (44%) reported no change/minimal improvement. Improvements were observed in WPI (-1.9, ES 0.4), SSS (-1.2, ES 0.6), fatigue (-0.8, p =.014) and self-efficacy for physical activity (1.4, ES 0.4). There was a significant trend of reduced WPI, SSS, pain and fatigue across the four time-points, but no additional improvements from 12 to 24-month follow-up. Participants who had completed the VTP demonstrated small to moderate improvements in symptom burden and FM-severity from baseline to 24-month follow-up. Trial registration number: ISRCTN96836577 https://doi.org/10.1186/ISRCTN96836577, prospectively registered 12.07.2016.
Combined transrectal ultrasound and radiomics model for evaluating the therapeutic effects of neoadjuvant chemoradiotherapy in locally advanced rectal cancer
Authors: Abuliezi Dilimire , She Yufen , Liao Zhongfan , Luo Yuan , Yang Yin , Huang Qin , Tao Anqi , Zhuang Hua
Published: January 2025

Purpose

This study aimed to explore a combined transrectal ultrasound (TRUS) and radiomics model for predicting tumor regression grade (TRG) after neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC).

Methods

Among 190 patients with LARC, 53 belonged to GRG and 137 to PRG. Eight TRUS parameters were identified as statistically significant (P < 0.05) for distinguishing between the groups, including PSVpre, LDpost, TDpost, CEUS-IGpost, LD change rate, TD change rate, RI change rate, and CEUS-IG downgrade. The accuracies of these individual parameters in predicting TRG were 0.42, 0.62, 0.56, 0.68, 0.67, 0.70, 0.63, and 0.71, respectively. The AUC values were 0.596, 0.597, 0.630, 0.752, 0.686, 0.660, 0.650, and 0.666, respectively. The multi-parameter ultrasonic logistic regression (MPU-LR) model achieved an accuracy of 0.816 and an AUC of 0.851 (95% CI: [0.792–0.909]). The optimal pre- and post-treatment radiomics models were RF (Mean-PCA-RFE-6) and AE (Zscore-PCA-RFE-12), with accuracies of 0.563 and 0.596 and AUCs of 0.601 (95% CI: [0.561–0.641]) and 0.662 (95% CI: [0.630–0.694]), respectively. The combined model (US-RADpre-RADpost) showed the highest predictive power with accuracy and AUC of 0.863 and 0.913.

Conclusions

The combined model based on TRUS and radiomics demonstrated remarkable predictive capability for TRG after NCRT. It serves as a precision tool for assessing NCRT response in patients with LARC, impacting treatment strategies.
Cost effectiveness of different treatment strategies with natalizumab for pregnant women with multiple sclerosis
Authors: Walbaum Magdalena , Madhukar Anushka , Dobson Ruth , Cyhlarova Eva , Castro-Aldrete Laura , Santuccione Chadha Antonella , Knapp Martin
Published: January 2025

Background

The management of multiple sclerosis (MS) during pregnancy poses significant challenges. This study aimed to evaluate the cost-effectiveness of three natalizumab treatment strategies during pregnancy from the UK healthcare system’s perspective.

Methods

A Markov model was developed to assess the health outcomes and costs associated with three treatment strategies: continuous natalizumab treatment throughout pregnancy, treatment until the first trimester followed by discontinuation, and discontinuation at conception with resumption post-pregnancy. The model incorporated data on relapse rates, disability progression, costs and quality-adjusted life years (QALYs). Sensitivity analyses were conducted.

Results

Continuing natalizumab throughout pregnancy was the most cost-effective strategy, yielding the highest incremental QALY gains and the lowest incremental cost per QALY (£1713 per QALY), with a net monetary benefit of £743. The sensitivity analyses confirmed the robustness of these findings and the use of generic or biosimilar forms of natalizumab further reinforced the cost-effectiveness of continuous treatment, with the biosimilar option proving cost-saving.

Conclusion

Continuing natalizumab treatment throughout pregnancy is the most cost-effective approach for managing MS in pregnant women. These findings should inform clinical guidelines and support healthcare providers and women with MS planning their family in making evidence-based decisions to improve the management of MS during pregnancy.
Challenges in multinational rare disease clinical studies during COVID-19: regulatory assessment of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease
Authors: Schoser Benedikt , Attarian Shahram , Graham Ryan , Holdbrook Fred , Goldman Mitchell , Díaz-Manera Jordi ,   The ATB200-03 study group
Published: January 2025

PROPEL (ATB200-03; NCT03729362) compared the efficacy and safety of cipaglucosidase alfa plus miglustat (cipa + mig), a two-component therapy for late-onset Pompe disease (LOPD), versus alglucosidase alfa plus placebo (alg + pbo). The primary endpoint was change in 6-min walk distance (6MWD) from baseline to week 52. During PROPEL, COVID-19 interrupted some planned study visits and assessment windows, leading to delayed visits, make-up assessments for patients who missed ≥ 3 successive infusions before planned assessments at weeks 38 and 52, and some advanced visits (end-of-study/early-termination visits). These were remapped to the respective planned visits. To evaluate if remapping may have overestimated treatment effects, we conducted post hoc analyses using a mixed-effect model for repeated measures based on actual time points of assessments. In this post hoc analysis, estimated mean treatment difference between cipa + mig and alg + pbo for change from baseline to week 52 in 6MWD was 11.7 m (95% confidence interval [CI] − 1.0 to 24.4; p = 0.072). In the original published analyses, between-group difference using last observation carried forward was 13.6 m (95% CI − 2.8 to 29.9; p = 0.071 [p value from separate non-parametric analysis of covariance]). Both statistical analysis approaches led to similar results and consistent conclusions, confirming the efficacy of cipa + mig for adults with LOPD. NCT03729362; trial start date: December 4, 2018.

Trial registration number
Effect of education program regarding pathological jaundice on nurses’ performance and neonates’ bilirubin-induced neurological dysfunction
Authors: Ebrahim Nora Abd El-Alim , Bayoumi Madiha Hassan , Metwally Hanan El-Sayed
Published: January 2025

Both term and preterm infants are susceptible to pathological jaundice, a frequent condition that can cause long-lasting neurological damage. A novel treatment for indirect pathological hyperbilirubinemia is bilisphere phototherapy, which lowers total serum bilirubin just as well as exchange transfusions. A quasi-experimental research design was utilized in the current study. This study was conducted in Neonatal Intensive Care Unit at Benha Specialized Pediatric Hospital. A convenient sample of all available nurses (60) working in the previously mentioned setting. A purposive sample of neonates (90) with pathological jaundice which would be divided into control and study groups. Three tools were used: Tool I: A structured interview questionnaire sheet, Tool II: observational checklist for caring neonates with pathological jaundice, and Tool III: neonatal outcomes assessment sheet. There was a positive correlation between nurses’ total performance regarding pathological jaundice and bilisphere phototherapy at pre-/post-education program implementation. Additionally, there were a positive correlation between neonates’ outcomes in the study group and nurses’ total performance post-program implementation.

Conclusion the education program regarding pathological jaundice was effective in improving nurses’ performance and neonates’ bilirubin-induced neurological dysfunction post compared to pre-education program implementation.

What is Known:• Pathological jaundice had directly effect on neurological status in neonates as aresults of accumulated bilirubin in basal gangelia in brain and bilirubin induced neurological dysfunction score considered important tool to indicate acute bilirubin encephalopathy.

What is New:• Education programs and periodic training to medical team provide improvement their performance, nurse had significant role to provide neonates care in NICU. So, improve nurses performance lead to improve neonate outcomes.• Bilisphere phototherapy is an important device which had positive outcomes in pediatrics which improve neonates’ health status, but its effect depends on provided effective nursing practice during therapy.• Pathological jaundice management with bilisphere phototherapy and bilirubin induced neurological dysfunction score working together to provide optimal care for neonates, which bilisphere phototherapy decrease bilirubin level and BIND score assess neurological status and detect any abnormalites during therapy.
Exploring the interactions of rapamycin with target receptors in A549 cancer cells: insights from molecular docking analysis
Authors: Ganesh Sanjeev K. , Devi C. Subathra
Published: January 2025

Rapamycin, a macrocyclic antibiotic derived from the actinomycetes Streptomyces hygroscopicus, is a widely used immunosuppressant and anticancer drug. Even though rapamycin is regarded as a multipotent drug acting against a broad array of anomalies and diseases, the mechanism of action of rapamycin and associated pathways have not been studied and reported clearly. Also reports on the binding of rapamycin to cancer cell receptors are limited to the serine/threonine protein kinase mTORC1. Hence, to uncover the exact potential of rapamycin in cancer therapy, a series of cell culture and in silico studies were conducted to identify other receptors capable of binding to rapamycin. Through molecular docking and simulations, it was found that the receptors EGFR, FKBP12, MET, FGFR, ROS1 and ALK were capable of binding with rapamycin. The findings from the current study provides new insights in modern cancer research and therapy. This could also facilitate in understanding the possible action mechanisms of rapamycin in other diseases such as neurovegetative diseases, autoimmune diseases, etc.
First assessment of the prevalence of haemosporidian infections in Accipitriformes raptors in Greece
Authors: Markakis Grigorios , Palinauskas Vaidas , Aželytė Justė , Symeonidou Isaia , Sutkaitytė Viltė , Gelasakis Athanasios I. , Komnenou Anastasia , Papadopoulos Elias
Published: January 2025

Haemosporidians, a group of vector-borne parasites that parasitize the blood cells and internal organs of various animal species, are reported to cause severe pathology in raptors. Species belonging to the genera Plasmodium, Haemoproteus and Leucocytozoon are the ones of greatest wildlife importance. The common buzzard (Buteo buteo) and the Eurasian sparrowhawk (Accipiter nisus) are the most numerous raptor species in Europe. Reliable data is lacking for many raptor species in Greece. The aim of this study was to assess, for the first time, the prevalence and geographical distribution of haemosporidian infection (mainly Leucocytozoon and Plasmodium) in these two avian species in Greece, in correlation with the risk factors of age and sex. In total, 62 common buzzards and 26 Eurasian sparrowhawks were included in this study, all being admitted for treatment at a Greek Wildlife Rehabilitation Center. Blood samples were collected and microscopical analysis was performed after staining blood smears with Giemsa. DNA was extracted from each sample and a fraction of the mitochondrial cytochrome b gene was amplified by a nested PCR protocol. All positive samples were subjected to sequencing. Total prevalence of haemosporidian infection by morphological and molecular examination was 59% and 73.9%, respectively. Binary logistic regression was carried out. The most prevalent infection was by Leucocytozoon spp. Most of the samples had mixed infections. The isolated genetic lineages of Leucocytozoon spp. were BUBT2, BUBT3, MILVUS01, ACNI1, BUBO01 and MILANS04. The detected genetic lineages of Plasmodium spp. were TURDUS1, BT7 and DONANA02. A new genetic lineage, BUTBUT17, was also identified.
Learning to cooperate against ensembles of diverse opponents
Authors: Perera Isuri , de Nijs Frits , García Julian
Published: January 2025

The emergence of cooperation in decentralized multi-agent systems is challenging; naive implementations of learning algorithms typically fail to converge or converge to equilibria without cooperation. Opponent modeling techniques, combined with reinforcement learning, have been successful in promoting cooperation, but face challenges when other agents are plentiful or anonymous. We envision environments in which agents face a sequence of interactions with different and heterogeneous agents. Inspired by models of evolutionary game theory, we introduce RL agents that forgo explicit modeling of others. Instead, they augment their reward signal by considering how to best respond to others assumed to be rational against their own strategy. This technique not only scales well in environments with many agents, but can also outperform opponent modeling techniques across a range of cooperation games. Agents that use the algorithm we propose can successfully maintain and establish cooperation when playing against an ensemble of diverse agents. This finding is robust across different kinds of games and can also be shown not to disadvantage agents in purely competitive interactions. While cooperation in pairwise settings is foundational, interactions across large groups of diverse agents are likely to be the norm in future applications where cooperation is an emergent property of agent design, rather than a design goal at the system level. The algorithm we propose here is a simple and scalable step in this direction.
Defining the caudal limits of the endoscopic endonasal approach to the craniovertebral junction: anatomic study correlating radiographic measures
Authors: Alsavaf Mohammad Bilal , Abouammo Moataz D. , Gosal Jaskaran Singh , Bhuskute Govind S. , Biswas Chandrima , Mansur Guilherme , VanKoevering Kyle K. , Wu Kyle C. , Carrau Ricardo L. , Prevedello Daniel M.
Published: January 2025

Objective

The endoscopic endonasal approach (EEA), has become the preferred alternative to traditional open and transoral approaches to the ventral craniovertebral junction (CVJ) region. However, preoperative prediction of the limitations of caudal reach remains challenging. This cadaveric study aimed to quantify the CVJ area of exposure and access afforded by the EEA, evaluate the accuracy of previously described radiographic anthropometric lines, and identify the lowest limit of the EEA corridor.

Methods

Endoscopic endonasal dissections of the CVJ were completed in 35 cadaveric specimens. The area of exposure (AoE) and caudal-most reach were measured using a navigation system. Radiographic measurements included the distance of the odontoid process from the hard palate, length of the hard palate, distance of the lowest point reached from the hard palate level, and angles such as the nasopalatine line (NPL) angle, nasoaxial line (NAxL) angle, nostril-hard palate line (NTL) angle, and rhinopalatine line (RPL) angle.

Results

The mean CVJ AoE was 931.22 ± 79.36 mm2. The NPL, NAxL, and RPL angles showed significant negative correlations with the distance of the odontoid process from the hard palate line (r = -0.521, p = 0.001; r = -0.538, p = 0.001; r = -0.500, p = 0.002, respectively), while the NTL angle did not (r = -0.241, p = 0.162). No significant correlation was found between achieved AoE via EEA and NPL, NAxL, NTL, or RPL (p > 0.05). Importantly, hard palate length was the sole predictor of CVJ AoE variability (r = -0.416, p = 0.013), with shorter lengths associated with increased exposure. The mean distance of the lowest point reached in the AoE from the hard palate level was 9.47 ± 1.24 mm.

Conclusions

This anatomic study highlights the variability in CVJ anatomy and the limitations of using previously defined radiographic anthropometric lines for predicting the caudal limits of the EEA. Hard palate length emerged as the only reliable predictor of the surgical area of exposure via the endonasal corridor. Clinical studies are warranted to validate these findings and define the potential need for adjunctive surgical routes in managing complex CVJ pathologies.
Evaluating economies of scope and potential merger: an alternative approach
Authors: Sadeghi Jafar , Toloo Mehdi , Sahoo Biresh K.
Published: January 2025

In data envelopment analysis literature, the estimation of economies of scope involves comparing two frontiers: one for diversified firms producing two outputs together (the diversified frontier) and the other involving additive firms (the additive frontier). A firm’s scope economies can be assessed by comparing the costs of its outputs against these two frontiers. If the cost for the additive frontier exceeds or falls short of that for the diversified frontier, one can determine the presence or absence of scope economies for the diversified firm. However, constructing the additive frontier requires the assumption that the cost of joint production by a diversified firm equals the cost of separate production by specialized firms. In the absence of such an additive cost structure in empirical studies, scope economies evaluation becomes problematic. To address this, we propose an alternative measurement scheme. Using the free disposability postulate of production theory, our scheme creates two sets of virtual specialized firms from the observed diversified firms, then updates them within their respective specialized firm sets. This approach enables an evaluation of a firm's scope economies by comparing the cost of separate production against updated specialized technologies with the joint production cost against diversified technology. Finally, the scheme also allows an examination of whether a merger between any two specialized firms would be profitable.
Testing for heterogeneity in data envelopment analysis
Authors: Mohsenirad Saman , Triantis Konstantinos
Published: January 2025

This paper introduces a comprehensive framework for detecting and conceptualizing heterogeneity in data envelopment analysis (DEA), aligning with the microeconomic production theory. Despite DEA’s significant advantage in evaluating DMUs based on their efficiency without assuming a specific functional form of technology, it critically relies on the comparability of these units. We address the persistent issue in DEA modeling that stems from the assumption of homogeneity among DMUs, which is often untested. We propose a novel methodological approach that serves as a testing framework for heterogeneity, predicated on minimal assumptions about data randomness. This framework provides a means to examine the biases introduced by technological disparities among DMUs and offers an approach for practitioners to ensure the validity of DEA modeling across diverse technological settings. This approach not only uncovers biases from technological differences but also serves as a preliminary step to enhance methods like clustering, aiding practitioners in verifying DEA's applicability across varied technologies.
Assessing cyber attack vulnerabilities of distributed generation in grid-connected systems
Authors: Maghami Mohammad Reza , Mutambara Arthur Guseni Oliver , Gomes Chandima
Published: January 2025

The widespread integration of solar PV, a type of distributed generation, is becoming more common in power grids, but this is raising concerns about their vulnerability to cyberattacks. The impact of widespread solar PV integration on the resilience of medium voltage power systems against cyberattacks remains largely unknown, particularly in the context of South Africa. This research aims to explore how solar PV integration affects the vulnerability of South Africa's power grid to cyber-attacks, during worst conditions, focusing on voltage stability, short circuits, and power losses. A static and dynamic power flow analysis was conducted on a model system consisting of two 132/11 kV transformers, four feeders, and 81 loads connected to the 11 kV busbar. The analysis of static power flow reveals that the majority of nodes have violations, particularly feeders 1 and 4. However, when solar PV penetration (PVP) reaches 100%, nodes with voltage violations are brought within the acceptable range. Moreover, the highest power loss is 412 kW, occurring at zero PVP during peak loads. The dynamic simulation results indicate that certain nodes still have violations even with 100% PVP. Feeder 1 is at the greatest risk of voltage collapse due to a cyber-attack, followed by feeder 4. In order to address issues with the network, multi-objective optimization was used to determine the optimal placement for tie-lines interconnections. This strategy shows that not only the power loss of the system significantly reduced by 50% but also the voltage profile of the system shifts to an acceptable level and is safe for any cyberattack. Further study may consider other mitigation techniques such as energy storage to mitigate the challenges beside the Tie line interconnection with minimum cost.
Sacubitril/valsartan in a wide spectrum of heart failure patients (from mechanisms of action to outcomes in specific populations)
Authors: Rajzer Przemyslaw , Biegus Jan
Published: January 2025

Heart failure (HF) represents a significant global health challenge, characterized by high morbidity and mortality rates, decreased quality of life and a significant financial and economic burden. The prevalence of HF continues to rise, driven by an ageing population and an increasing burden of comorbidities such as hypertension, diabetes and obesity. Understanding the complex pathophysiology and developing effective treatments are critical for improving patient outcomes, yet the range of effective, life-prolonging medication classes has remained mostly constant in the last few decades. The introduction of angiotensin receptor neprilysin inhibitors (ARNI) was a major breakthrough in HF management, for the first time targeting the natriuretic peptide system in addition to the renin–angiotensin–aldosterone pathway to potentiate the effects of older drug classes. ARNI shows superiority in clinical outcomes compared to previous guideline-directed therapies, especially in patients with reduced ejection fraction (EF). It has now been implemented into international guidelines, endorsing its use in patients with HF and reduced ejection fraction (HFrEF) and HF with mildly reduced ejection fraction (HFmrEF). This review summarises the mechanism of action of Sac/Val, presents key clinical trials in a range of patient populations and HF aetiologies and outlines gaps in knowledge and potential novel uses of Sac/Val.
What explains recent trends in income inequality in the European Union?
Authors: Filauro Stefano , Parolin Zachary , Valetto Pietro
Published: January 2025

We investigate trends in income inequality in the European Union (EU) from 2007 to 2019. Using EU-SILC data, we find that EU-wide inequality declined between 9 and 20%, depending on the inequality measure applied, despite rising within-country income inequality during the same period. Applying a series of decomposition techniques, we find that between-country convergence in pre-tax/transfer incomes fully explains the declining EU-wide inequality. Changes in tax and transfer systems, in contrast, contributed to marginally higher inequality in 2019 compared to 2007. Nonetheless, the 10th percentile of the EU-wide income distribution grew six times the rate of the 90th percentile, a product of widespread earnings gains among residents of lower-income EU Member States. Re-centered influence functions and Kitigawa-Oaxaca-Blinder analyses reveal that those earnings gains are not due to specific compositional or employment changes but rather are due to rising earnings returns to employment in lower-income Member States. Despite the contribution of between-country income convergence in reducing EU-wide inequality between 2007 and 2019, however, within-country income disparities continue to explain the larger share of EU-wide inequality levels in 2019. Thus, reducing within-country economic disparities is increasingly important for achieving further reductions in EU-wide inequality moving forward.
First Step on the Way to Identify Dermatophytes Using Odour Fingerprints
Authors: Machová Lenka , Gaida Meriem , Semerád Jaroslav , Kolařík Miroslav , Švarcová Michaela , Jašica Andrej , Grasserová Alena , Awokunle Hollá Sandra , Hubka Vit , Stefanuto Pierre-Hugues , Cajthaml Tomáš , Focant Jean-François , Wennrich Adéla
Published: January 2025

The clinical diagnosis of dermatophytosis and identification of dermatophytes face challenges due to reliance on culture-based methods. Rapid, cost-effective detection techniques for volatile organic compounds (VOCs) have been developed for other microorganisms, but their application to dermatophytes is limited. This study explores using VOCs as diagnostic markers for dermatophytes. We compared VOC profiles across different dermatophyte taxa using solid-phase microextraction (SPME) and advanced analytical methods: gas chromatography-mass spectrometry (GC–MS) and comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-TOFMS). We analyzed 47 dermatophyte strains from 15 taxa grown on sheep wool, including clinically significant species. Additionally, we examined phylogenetic relationships among the strains to correlate genetic relatedness with metabolite production. Our results showed that GC×GC-TOFMS offered superior resolution but similar differentiation of VOC profiles compared to GC–MS. VOC spectra allowed reliable distinction of taxonomic units at the species level and below, however, these distinctions showed only a slight correlation with phylogenetic data. We identified pan-dermatophyte and species- or strain-specific VOC profiles, indicating their potential for rapid, non-invasive detection of dermatophyte infections, including epidemic strains. These patterns could enable future taxa-specific identification. Our study highlights the potential of VOCs as tools for dermatophyte taxonomy and diagnosis.
Enhancing model performance through date fusion in multispectral and RGB image-based field phenotyping of wheat grain yield
Authors: Heinemann Paul , Prey Lukas , Hanemann Anja , Ramgraber Ludwig , Seidl-Schulz Johannes , Noack Patrick Ole
Published: January 2025

This study assessed the potential of multispectral (MS) and RGB imagery acquired by unmanned aerial vehicles (UAVs) for predicting wheat grain yield (GY) in field trials. We investigated the influence of single-date measurements and optimal multi-date strategies across diverse locations and years in southeast and eastern Germany. UAV-based MS and RGB data were collected throughout the growing season, and machine learning models were developed using vegetation indices to predict GY. Results revealed that the accuracy of single-date predictions varied, with later stages, especially grain-filling, demonstrating higher performance. Combining data from multiple dates improved GY prediction, and especially the inclusion of June acquisitions (likewise around grain-filling phase) consistently enhances the prediction accuracy of multi-date models. However, the optimal combination of dates was found to be year- and location-specific. Overall, MS data slightly outperformed RGB data, although RGB showed advantages in specific instances, particularly during later growth stages. This study provides valuable insights for optimizing UAV-based phenotyping in wheat breeding trials, highlighting the importance of strategic measurement timing and sensor selection for accurate GY prediction.
Domain-specific implications of error-type metrics in risk-based software fault prediction
Authors: Phung Khoa , Ogunshile Emmanuel , Aydin Mehmet E.
Published: January 2025

In software development, Software Fault Prediction (SFP) is essential for optimising resource allocation and improving testing efficiency. Traditional SFP methods typically use binary-class models, which can provide a limited perspective on the varying risk levels associated with individual software modules. This study explores the impacts of Error-type Metrics on the fault-proneness of software modules in domain-specific software projects. Also, it aims to enhance SFP methods by introducing a risk-based approach using Error-type Metrics. This method categorises software modules into High, Medium, and Low-Risk categories, offering a more granular and informative fault prediction framework. This approach aims to refine the fault prediction process and contribute to more effective resource allocation and project management in software development. We explore the domain-specific impact of Error-type Metrics through Principal Component Analysis (PCA), aiming to fill a gap in the existing literature by offering insights into how these metrics affect machine learning models across different software domains. We employ three machine learning models - Support Vector Machine (SVM), Random Forest (RF), and Extreme Gradient Boosting (XGB) - to test our approach. The Synthetic Minority Over-sampling Technique (SMOTE) is used to address class imbalance. Our methodology is validated on fault data from four open-source software projects, aiming to confirm the robustness and generalisability of our approach. The PCA findings provide evidence of the varied impacts of Error-type Metrics in different software environments. Comparative analysis indicates a strong performance by the XGB model, achieving an accuracy of 97.4%, a Matthews Correlation Coefficient of 96.1%, and an F1-score of 97.4% across the datasets. These results suggest the potential of the proposed method to contribute to software testing and quality assurance practices. Our risk-based SFP approach introduces a new perspective to risk assessment in software development. The study’s findings contribute insights into the domain-specific applicability of Error-type Metrics, expanding their potential utility in SFP. Future research directions include refining our fault-counting methodology and exploring broader applications of Error-type Metrics and our proposed risk-based approach.
Factors associated with lower forced vital capacity in children and adults with Duchenne muscular dystrophy using non-invasive ventilation: a multicenter analysis
Authors: Sunkonkit Kanokkarn , Hurvitz Manju , Defante Andrew , Orr Jeremy , Chakraborty Abhishek , Amin Reshma , Bhattacharjee Rakesh
Published: January 2025

Background

Reduced forced vital capacity (FVC) is associated with morbidity and mortality in individuals with Duchenne muscular dystrophy (DMD). Non-invasive ventilation (NIV) is often prescribed for the treatment of sleep-disordered breathing (SDB), and chronic respiratory insufficiency. Despite the common practice of initiating NIV later in the progression of DMD, the factors influencing FVC subsequent to the commencement of NIV remain unclear.

Objective

To evaluate the demographic, clinical and socioeconomic determinants of FVC% predicted across several cohorts of DMD children and adults prescribed NIV.

Methods

A multicenter retrospective review of individuals with DMD prescribed NIV was performed between February 2016 to October 2020. Patients were identified from three sites: The Hospital for Sick Children, Canada; Rady Children’s Hospital San Diego, USA; and University of California San Diego Health, USA. Multivariate regression analysis was performed to determine factors that influence FVC.

Results

Fifty-nine male patients with DMD prescribed NIV (mean ± SD for age and BMI was 20.1 ± 6.7 years and 23.8 ± 8.8 kg/m2) were included. Following multivariate analysis, a lower FVC% predicted was associated with older age (β = -1.44, p = 0.001), presence of scoliosis (β = -16.94, p = 0.002), absent deflazacort prescription (β = 14.43, p = 0.009), and use of in-ex sufflator (β = -39.73, p < 0.001), respectively.

Conclusion

In our study, several factors were associated with reduced FVC% predicted in a DMD population using NIV. Future, prospective, longitudinal studies are imperative to comprehend the trajectory of FVC% predicted over time in individuals with DMD using NIV.
Mechanical Cell Interactions on Curved Interfaces
Authors: Buenzli Pascal R. , Kuba Shahak , Murphy Ryan J. , Simpson Matthew J.
Published: January 2025

We propose a simple mathematical model to describe the mechanical relaxation of cells within a curved epithelial tissue layer represented by an arbitrary curve in two-dimensional space. This model generalises previous one-dimensional models of flat epithelia to investigate the influence of curvature for mechanical relaxation. We represent the mechanics of a cell body either by straight springs, or by curved springs that follow the curve’s shape. To understand the collective dynamics of the cells, we devise an appropriate continuum limit in which the number of cells and the length of the substrate are constant but the number of springs tends to infinity. In this limit, cell density is governed by a diffusion equation in arc length coordinates, where diffusion may be linear or nonlinear depending on the choice of the spring restoring force law. Our results have important implications about modelling cells on curved geometries: (i) curved and straight springs can lead to different dynamics when there is a finite number of springs, but they both converge quadratically to the dynamics governed by the diffusion equation; (ii) in the continuum limit, the curvature of the tissue does not affect the mechanical relaxation of cells within the layer nor their tangential stress; (iii) a cell’s normal stress depends on curvature due to surface tension induced by the tangential forces. Normal stress enables cells to sense substrate curvature at length scales much larger than their cell body, and could induce curvature dependences in experiments.
The Impact of Lesion-Specific and Sampling-Related Factors on Success of Salivary Gland Fine-Needle Aspiration Cytology
Authors: Mayer Marcel , Alfarra Mohammad Marwan , Möllenhoff Kathrin , Engels Marianne , Arolt Christoph , Quaas Alexander , Wolber Philipp , Jansen Louis , Nachtsheim Lisa , Grosheva Maria , Klussmann Jens Peter , Shabli Sami
Published: January 2025

Purpose

Ultrasound-guided fine-needle aspiration cytology (FNAC) is a widely used diagnostic procedure which facilitates the differentiation of salivary gland lesions. Although the performance of salivary gland FNAC (SG-FNAC) has improved since the introduction of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), the range of the reported performance is still wide. Therefore, the aim of this study was to determine lesion- and sampling-related factors that influence the success of SG-FNAC.

Methods

All SG-FNAC cases performed in a tertiary referral hospital between September 1st, 2011, and August 31st, 2022, were retrospectively identified. Demographic, histopathological, lesion-specific, and sampling-related data were retrieved from the clinical charts. Cytopathological reports were categorized according to the MSRSGC. The risk of malignancy (ROM), the performance measures, and factors influencing the success of SG-FNAC were calculated.

Results

Overall, 1289 cases with histopathological follow-up diagnosis (out of 1952 SG-FNACs) were included. The ROM was: non-diagnostic = 23.9%, non-neoplastic = 4.4%, atypia of undetermined significance (AUS) = 34.5%, neoplasm-benign = 1.0%, neoplasm-salivary gland neoplasm of uncertain malignant potential (SUMP) = 15.3%, suspicious for malignancy = 74.1%, malignant = 96.2%. The sensitivity, specificity, accuracy, positive, and negative predictive value for differentiating benign from malignant lesions (excluding lesions categorized as AUS and SUMP) were 87.5%, 97.7%, 96.3%, 85.0%, and 98.1%, respectively. A larger lesion size (OR (95% CI) = 1.21 (1.06–1.39), p = 0.004), a higher number of obtained slides (OR (95% CI) = 1.31 (1.17–1.46), p < 0.001), and the physician performing the FNAC (p = 0.047) were independent predictors for a higher success, while localization of the lesion within the submandibular compared to the parotid gland (OR (95% CI) = 0.38 (0.19–0.77), p = 0.008) was an independent predictor for lower success of SG-FNAC.

Conclusion

This is the largest single-center study evaluating SG-FNAC performance to date. It identified independent lesion-and sampling-related factors influencing the success of SG-FNAC. Knowledge of those can improve performance of the procedure.
Barriers impacting breast cancer screening during the COVID-19 pandemic among Hispanic women in New Jersey
Authors: Perez-Tucker Raquel , Nelson Anna P. , Lee Jerry W. , Wiafe Seth A. , Handysides Daniel G.
Published: January 2025

Hispanic women in the United States have been identified as an ethnic group experiencing disproportionately higher mortality rates of breast cancer. These higher rates have been linked to contextual factors that delay breast cancer screening utilization. The COVID-19 pandemic posed a significant disruption to obtaining breast cancer screening affecting utilization of these services especially among minorities. Our cross-sectional study utilized the socio-ecological model (SEM) as a framework to identify barriers influencing delayed utilization using a comprehensive self-administered survey, which was completed among 155 Hispanic and 147 non-Hispanic White women, aged 50 and older, and who resided in the state of New Jersey during the COVID-19 pandemic. Cancer screening attitudes and the extent in which numerous barriers affected utilization of breast cancer screening services during the pandemic were assessed using logistic regression and factor analysis. The analysis confirmed barriers that included low socio-economic status, lack of health insurance, low education attainment, unemployment, limited access to health care services, cancer fatalism, fear of acquiring COVID-19, and linguistic barriers. The findings of this study validate the recommendation of using multi-pronged interventions based on the SEM framework to address both individual and systemic barriers to screening. Breast cancer screening education, resources to access health services and health insurance options may be applied to these vulnerable populations to reduce barriers and facilitate yearly breast cancer screening.
Cognitive Health After Cerebellar Stroke: Potential Link Between Socio-Educational Status and Memory Outcome
Authors: Voruz Philippe , Constantin Ioana Medeleine , Chassot Emilie , Thomasson Marine , Assal Frédéric , Péron Julie Anne
Published: January 2025

While deficits in episodic memory have been noted following cerebellar damage, there is a lack of research systematically exploring the socio-demographic and cognitive profiles of patients with such impairments. This study aimed to differentiate between chronic-phase cerebellar stroke patients with and without verbal episodic memory deficits, and to determine whether those with deficits exhibit distinct socio-demographic and clinical profiles, thereby identifying potential factors associated with these impairments. Data from 15 cerebellar stroke patients in the CEREBEMO cohort were analyzed, with participants categorized into two groups based on verbal episodic memory performance: deficits (n = 8) and no deficits (n = 7). Statistical analyses, including Generalized Linear Mixed Models and Chi-Squared tests, compared socio-demographic and neuropsychological variables between the groups. Significant differences were observed in socio-educational levels, with a higher proportion of patients with memory deficits at intermediate education levels. Moreover, patients with memory deficits performed worse on the Montreal Cognitive Assessment and the Trail Making Test, indicating overall lower cognitive efficiency and slower processing speed. Post-hoc analysis showed that, despite the limited sample size, our sample effectively detected a significant difference between the two groups with high statistical power. These findings highlight potential socio-educational and cognitive factors associated with memory impairments following cerebellar stroke.