This paper reviews the dynamics of a single isotropic and homogeneous scalar field $\phi \left(t\right)$ in the context of cosmological models. A non-standard approach to the solution of the Einstein–Klein–Gordon equations is described which uses the scalar field as the evolution parameter for cosmic dynamics. General conclusions about the qualitative behaviour of the solutions can be drawn, and examples of how to obtain explicit solutions for some cosmological models of interest are given. For arbitrary potentials, analytical results can be obtained from the slow-roll approximation by using a series expansion for the Hubble parameter $H\left[\phi \right]$, from which a quantitative estimate for the number of e-folds of expansion is obtained. This approach is illustrated with the examples of quadratic potentials and hilltop models, with special consideration of Higgs-type potentials. The GUT-scale is shown to come out of such a model quite naturally. Finally, it is discussed how to find scalar potentials giving rise to a predetermined scalar-field behaviour and the associated evolution of the scale factor. Full article

In many (remote) rural areas of Europe and the world, rural communities are facing various challenges. One response is residents leaving their communities. However, there are also many empirical examples of residents staying, launching project initiatives, developing new solutions and experimenting with new practices. This is what we call social innovation. What experiences do actors have in these processes? Can we speak of empowerment? To what extent can such initiatives have an impact on community development? In this article, we explore these questions, for which there is little related empirical research. By applying a multi-sited individualising comparison to case studies in three European countries (Germany, Ireland and Portugal), we obtain empirical evidence of the following dimensions of empowerment that Avelino et al. outline conceptually: the achievement of autonomy, competence and relatedness and also impact, meaning and resilience. Often, however, it is not the individual actors for whom such effects can be reported. Rather, the social initiative as such or the local administration has acquired new skills and autonomy. Regarding community development, ‘pathways to impact’, such as infrastructure improvements and/or the creation of new employment opportunities and/or the influx of new residents, could be identified. However, this development often depended on both opportunity and the cooperation and goodwill of many stakeholders. Full article

Medical education acknowledges our need to teach our physicians about “social determinants of health” and “health care disparities”. However, educators often lack actionable training to address this need. We describe a faculty development activity, a health disparities journal club, using the jigsaw strategy with the intent of increasing awareness, encouraging self-directed learning, and inspiring future teaching of the subject to health professional learners. We completed six workshops at six individual hospitals, with 95 total attendees in medicine and numerous other health professions. Our evaluation asked trainees to: report the number of journal articles about health disparities they had read, excluding the assigned journal club articles, in the past 12 months, and to predict future plans for reading about health disparities. In total, 28.9% responded they had “never read” a prior article on health or healthcare disparities, while 54.2% responded “1–5 articles”. Many (60%) reported they would continue to investigate this topic. Our experience has demonstrated the utility and positive impact of a “flipped classroom” jigsaw method, showing it can be used successfully in Inter-Professional (IPE) Faculty Development to increase active exposure and discussion of the content. Additionally, this method promotes individual reflection and enhances continued collective engagement. Full article

This article attempts to answer the following question: why did the author of the apocryphon called 1 Apocryphal Apocalypse of John choose to efface himself and adopt John as his pseudonym? Why not Peter or Paul? This paper argues that the author of 1 Apocryphal Apocalypse of John intended to harness the audience attached to John, the seer of Revelation, by taking his name as a pseudonym. This paper sustains this claim by demonstrating that, in antiquity, each author had a specific pool of readers, often made out of friends and accolades of the author. Thus, authors’ names evoke an audience attached to them. When an author takes another person’s name to write under, he does so out of necessity, because he does not have an audience. But, when he takes another’s person name, he does so hoping to trick the audience of the impersonated into reading him. Based on this insight, this article concludes that the author of 1 Apocr. Apoc. John wanted the readers of canonical Revelation to engage with his work and that he achieved his purpose as evinced by the fact that the titles of both works share an uncanny resemblance, ranging from identical titles to similar wording. Since titles in antiquity were given to the works by their readers, the most logical explanation for canonical Revelation and 1 Apocr. Apoc. John having the same titles is that they both shared the same readers. Finally, this article argues that, in line with recent research on the use of pseudepigraphy in Jewish, Christian, and Roman contexts, the author of 1 Apocr. Apoc. John wanted to be read by CR’s readers because he wanted to expand, criticize, rework, and update CR’s eschatological discourse, exemplified by a close reading of how 1 Apocr. Apoc. John criticized, reworked, and updated CR’s presentation of the resurrection to bring it in harmony with late Christian reflection on the subject. Full article

Background: Aspergillus can cause fungal rhinosinusitis (FRS). We aimed to identify risk factors for sinonasal Aspergillus disease. Methods: Patients with a positive sinonasal mycological culture for Aspergillus species diagnosed in our hospital located in a continental climate were included in the 9-year retrospective study. Results: Of the 86 patients, 3 had invasive FRS (IFRS), 51 had fungal ball (FB) disease, and 32 had chronic rhinosinusitis with fungus (CFRS). In the IFRS group, all patients had a malignancy and were immunocompromised. Allergies, allergic rhinitis, asthma, nasal polyps, and the use of inhaled and nasal steroids were more common in the CFRS group, and IgE levels were greater than those in the FB and IRFS groups (p < 0.05). Conclusion: FB disease is a relatively symptom-free single-sinus disease among elderly individuals, and IFRS is dominant among immunocompromised patients. We discovered a third patient group, predominantly with nasal polyps, atopy, asthma, and elevated blood IgE and eosinophils, that did not fulfill the allergic FRS (AFRS) criteria. It is possible that a less fulminant category of underdiagnosed AFRS exists in cold climates. Treatment with local debridement is usually sufficient for FRS, apart from IFRS, and relapses are not common in cold climates. Full article

Immunoglobulin G-based monoclonal antibodies (mAbs) have been effective in treating various diseases, but their large molecular size can limit their penetration of tissue and efficacy in multifactorial diseases, necessitating the exploration of alternative forms. In this study, we constructed a phage display library comprising single-domain antibodies (sdAbs; or “VHHs”), known for their small size and remarkable stability, using a total of 1.6 × 10⁹ lymphocytes collected from 20 different alpacas, resulting in approximately 7.16 × 10¹⁰ colonies. To assess the quality of the constructed library, next-generation sequencing-based high-throughput profiling was performed, analyzing approximately 5.65 × 10⁶ full-length VHH sequences, revealing 92% uniqueness and confirming the library’s diverse composition. Systematic characterization of the library revealed multiple sdAbs with high affinity for three therapeutically relevant antigens. In conclusion, our alpaca sdAb phage display library provides a versatile resource for diagnostics and therapeutics. Furthermore, the library’s vast natural VHH antibody repertoire offers insights for generating humanized synthetic sdAb libraries, further advancing sdAb-based therapeutics. Full article

While FXR has shown promise in regulating bile acid synthesis and maintaining glucose and lipid homeostasis, undesired side effects have been observed in clinical trials. To address this issue, the development of intestinally restricted FXR modulators has gained attention as a new avenue for drug design with the potential for safer systematic effects. Our review examines all currently known intestinally restricted FXR ligands and provides insights into the steps taken to enhance intestinal selectivity. Full article

Unmanned aerial vehicles (UAVs) provide benefits through eco-friendliness, cost-effectiveness, and reduction of human risk. Deep reinforcement learning (DRL) is widely used for autonomous UAV navigation; however, current techniques often oversimplify the environment or impose movement restrictions. Additionally, most vision-based systems lack precise depth perception, while range finders provide a limited environmental overview, and LiDAR is energy-intensive. To address these challenges, this paper proposes VizNav, a modular DRL-based framework for autonomous UAV navigation in dynamic 3D environments without imposing conventional mobility constraints. VizNav incorporates the Twin Delayed Deep Deterministic Policy Gradient (TD3) algorithm with Prioritized Experience Replay and Importance Sampling (PER) to improve performance in continuous action spaces and mitigate overestimations. Additionally, VizNav employs depth map images (DMIs) to enhance visual navigation by accurately estimating objects’ depth information, thereby improving obstacle avoidance. Empirical results show that VizNav, by leveraging TD3, improves navigation, and the inclusion of PER and DMI further boosts performance. Furthermore, the deployment of VizNav across various experimental settings confirms its flexibility and adaptability. The framework’s architecture separates the agent’s learning from the training process, facilitating integration with various DRL algorithms, simulation environments, and reward functions. This modularity creates a potential to influence RL simulation in various autonomous navigation systems, including robotics control and autonomous vehicles. Full article

Due to the high mortality rate in Western countries, pancreatic cancer is considered one of the big killers, leaving patients and their families with little hope upon diagnosis. Although surgical and drug therapies are critical for cancer patients to improve life expectancy and alleviation of suffering, nutrition plays a key role in improving cancer treatment outcomes. This narrative review, conducted as part of the activities of the Italian Society of Human Nutrition (SINU) working group in oncology, focuses on the prevalence of vitamin malnutrition among pancreatic cancer patients. The results of the literature search show that pancreatic cancer patients are at a heightened risk of water-soluble vitamin deficiencies, particularly of vitamins B1, B3, and B6. Additionally, they also face an increased risk of deficiency of fat-soluble vitamins. Among these vitamins, the potential role of vitamin D in pancreatic cancer has garnered the most attention, with its plasma levels being identified as a significant factor in patient survival. Investigating vitamin nutritional status could provide valuable insights for incorporating nutritional approaches into the prevention and treatment of pancreatic cancer, thereby reducing the exacerbation of symptoms associated with the diagnosis. Full article

This paper works with functions defined in metric spaces and takes values in complete paranormed vector spaces or in Banach spaces, and proves some necessary and sufficient conditions for weak convergence of probability measures. Our main result is as follows: Let X be a complete paranormed vector space and $\Omega$ an arbitrary metric space, then a sequence $\left\{{\mu }_n\right\}$ of probability measures is weakly convergent to a probability measure $\mu$ if and only if $\underset{n\to \infty }{\lim }{\displaystyle {\int }_{\Omega }}g(s)d{\mu }_n={\displaystyle {\int }_{\Omega }}g(s)d\mu$ for every bounded continuous function g: Ω → X. A special case is as the following: if X is a Banach space, $\Omega$ an arbitrary metric space, then $\left\{{\mu }_n\right\}$ is weakly convergent to $\mu$ if and only if $\underset{n\to \infty }{\lim }{\displaystyle {\int }_{\Omega }}g(s)d{\mu }_n={\displaystyle {\int }_{\Omega }}g(s)d\mu$ for every bounded continuous function g: Ω → X. Our theorems and corollaries in the article modified or generalized some recent results regarding the convergence of sequences of measures. Full article

Prior research has suggested that resistance exercise may result in a temporary decrease in vascular function, as measured by flow-mediated dilation (FMD), among untrained young individuals. However, the immediate impact of combined elastic and weight resistance training on older adults remains insufficiently explored. We assessed vascular function before, after, and 30 min after acute exercise under three resistance conditions to evaluate whether a combination of weight and elastic resistance exercises has an acute effect on vascular function in older adults. Fourteen older adults (65.6 ± 2.9 years) executed three sets of 12 repetitions at 65% of one repetition maximum (1 RM) of the bench press (BP) exercise. Testing was performed on three separate days as follows: (1) barbell alone (BA); (2) barbell plus elastic bands (10% of 65% 1 RM) (BE10); and (3) barbell plus elastic bands (20% of 65% 1 RM) (BE20). A two-way (time × condition) repeated measures analysis of variance was employed to assess the time and condition effects on flow-mediated dilation (FMD) and pulse wave velocity (PWV). At 0 min post-exercise, FMD was significantly higher during BE10 than during BA (p < 0.05); however, at 30 min post-exercise, no significant difference (p ≥ 0.05) was observed between the three conditions. In each condition, FMD results did not differ significantly at different times (p ≥ 0.05). For FMD, the main effect of the condition (F[2,26] = 3.86, p = 0.034) and that of the time and condition (F[4,52] = 3.66, p = 0.011) were significant. For PWV, only the difference between the BA and BE10 conditions was significant at 0 min (p < 0.05). PWV increased from baseline in the BA condition (p < 0.05) but not significantly in the BE10 and BE20 conditions (p ≥ 0.05). Therefore, BA, BE10, and BE20 demonstrated various changes in vascular function. Long-term training intervention studies are needed to validate these findings. Full article

Neuroblastoma (NB) is the most commonly diagnosed extracranial solid tumor in children, accounting for 15% of all childhood cancer deaths. Although the 5-year survival rate of patients with a high-risk disease has increased in recent decades, NB remains a challenge in pediatric oncology, and the identification of novel potential therapeutic targets and agents is an urgent clinical need. The RNA-binding protein LIN28B has been identified as an oncogene in NB and is associated with a poor prognosis. Given that LIN28B acts by negatively regulating the biogenesis of the tumor suppressor let-7 miRNAs, we reasoned that selective interference with the LIN28B/let-7 miRNA interaction would increase let-7 miRNA levels, ultimately leading to reduced NB aggressiveness. Here, we selected (−)-epigallocatechin 3-gallate (EGCG) out of 4959 molecules screened as the molecule with the best inhibitory activity on LIN28B/let-7 miRNA interaction and showed that treatment with PLC/PLGA-PEG nanoparticles containing EGCG (EGCG-NPs) led to an increase in mature let-7 miRNAs and a consequent inhibition of NB cell growth. In addition, EGCG-NP pretreatment reduced the tumorigenic potential of NB cells in vivo. These experiments suggest that the LIN28B/let-7 miRNA axis is a good therapeutic target in NB and that EGCG, which can interfere with this interaction, deserves further preclinical evaluation. Full article

In practical applications, rapid prediction and optimization of heat transfer performance are essential for premixed methane impinging flame jets (PMIFJs). This study uses computational fluid dynamics (CFD) combined with a methane detailed chemical reaction mechanism (GRI–Mech 3.0) to study the equivalence ratio (Φ), Reynolds number (Re) of the mixture, and the normalized nozzle–to–plate distance (H/d) on the heat transfer performance of PMIFJs. Moreover, the Kriging model (KM) was used to construct a prediction model of PMIFJ heat transfer performance. A genetic algorithm (GA) was used to determine the maximum likelihood function (MLE) of the model parameters for constructing KM and identify the points with the maximum root mean square error (RMSE) as the new infilled points for surrogate–based optimization (SBO). Combining these methods to analyze the simulation results, the results show that the global heat transfer performance of PMIFJs is enhanced with the increase in Φ, the increase in Re, and the decrease in H/d. Sensitivity analysis points out that Re and Φ significantly affect enhanced heat transfer, while H/d has a relatively small effect. In addition, GA was also used to search for the optimal heat transfer performance, and the global heat transfer performance at specific conditions was significantly enhanced. This study deepens the understanding of the heat transfer mechanism of impinging flame jets and provides an efficient method framework for practical applications. Full article

Due to the high death rate associated with gastric cancer, a great deal of research has been conducted on this disease. The goal of this paper was to start a trimestral review of 2024 for the year that had just started. The scientific literature from 1 January 2024 was chosen with consideration of the the guidelines of the European Society of Medical Oncology (ESMO), which are updated with new findings but not systematically reviewed annually. We used the search term “gastric cancer” to find the most current publications in the PubMed database related to the prognosis and treatment of gastric cancer. As previously said, the only articles that satisfied the inclusion criteria were those from 2024. Articles with case reports were eliminated since they had nothing to do with our research. The treatment of gastric cancer is the focus of the majority of articles from 2024. The primary research axes include surgery and immunonutrition, immunotherapy and Helicobacter pylori, and therapeutic targets. Patients with GC may experience less psychological, social, and financial hardship if the recently identified markers discovered in circulation are better assessed and validated. This could be achieved by either including the markers in an artificial intelligence-based diagnostic score or by using them in conjunction with traditional diagnostic methods. Due to the rising death rate associated with GC, funding for research into diagnosis, prognosis, therapy, and therapeutic targets is essential. Full article

L-asparaginase is an essential drug used to treat acute lymphoid leukemia (ALL), a cancer of high prevalence in children. Several adverse reactions associated with L-asparaginase have been observed, mainly caused by immunogenicity and allergenicity. Some strategies have been adopted, such as searching for new microorganisms that produce the enzyme and applying protein engineering. Therefore, this work aimed to elucidate the molecular structure and predict the immunogenic profile of L-asparaginase from Penicillium cerradense, recently revealed as a new fungus of the genus Penicillium and producer of the enzyme, as a motivation to search for alternatives to bacterial L-asparaginase. In the evolutionary relationship, L-asparaginase from P. cerradense closely matches Aspergillus species. Using in silico tools, we characterized the enzyme as a protein fragment of 378 amino acids (39 kDa), including a signal peptide containing 17 amino acids, and the isoelectric point at 5.13. The oligomeric state was predicted to be a homotetramer. Also, this L-asparaginase presented a similar immunogenicity response (T- and B-cell epitopes) compared to Escherichia coli and Dickeya chrysanthemi enzymes. These results suggest a potentially useful L-asparaginase, with insights that can drive strategies to improve enzyme production. Full article

Erythropoiesis is initiated with the transformation of multipotent hematopoietic stem cells into committed erythroid progenitor cells in the erythroblastic islands of the bone marrow in adults. These cells undergo several stages of differentiation, including erythroblast formation, normoblast formation, and finally, the expulsion of the nucleus to form mature red blood cells. The erythropoietin (EPO) pathway, which is activated by hypoxia, induces stimulation of the erythroid progenitor cells and the promotion of their proliferation and survival as well as maturation and hemoglobin synthesis. The regulation of erythropoiesis is a complex and dynamic interaction of a myriad of factors, such as transcription factors (GATA-1, STAT5), cytokines (IL-3, IL-6, IL-11), iron metabolism and cell cycle regulators. Multiple microRNAs are involved in erythropoiesis, mediating cell growth and development, regulating oxidative stress, erythrocyte maturation and differentiation, hemoglobin synthesis, transferrin function and iron homeostasis. This review aims to explore the physiology of steady-state erythropoiesis and to outline key mechanisms involved in ineffective erythropoiesis linked to anemia, chronic inflammation, stress, and hematological malignancies. Studying aberrations in erythropoiesis in various diseases allows a more in-depth understanding of the heterogeneity within erythroid populations and the development of gene therapies to treat hematological disorders. Full article

Increasing attention is being given to reduce the specific energy consumption in desalination processes, which translates into greater use of exergy analysis. An exergetic analysis provides relevant information related to the influence of the efficiency of a single component in the global plant performance and in the exergy cost of the product. Therefore, an exergy analysis identifies the main improvement potentials in a productive thermodynamic process. Related to desalination technologies, many previous papers deal with the calculation of the parameters involved in the exergy analysis, the exergetic efficiency of different processes, plants, and technologies among them. However, different approaches for formulating the exergetic efficiency have been suggested in the literature, often without sufficient understanding and consistency. In this work, these formulations, applied to the main desalination components and processes, are compared and critically reviewed. Two definitions of exergy efficiency are applied to the desalination components of the three main thermal desalination processes (multieffect distillation–thermal vapour compression, multistage flash distillation, and direct-contact membrane distillation). The results obtained for the exergy efficiency of the MED-TVC, MSF, and DCMD processes for the input–output approach are 21.35%, 17.08%, and 1.28%, respectively, compared to the consumed–produced approach that presented 3.1%, 1.58%, and 0.37%, respectively. The consumed–produced approach seems to better fit the thermodynamic behaviour of thermal desalination systems. Full article

Calcitonin gene-related peptide (CGRP) has long been implicated in both the physiology and pathophysiology of the respiratory tract. The objective of our study was to determine the serum concentration of alpha CGRP (αCGRP) in cystic fibrosis (CF) that arises from mutations in the gene responsible for encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Currently, there are not many data in the literature about the role of CGRP in CF. The serum level of αCGRP was estimated using the enzyme-linked immunosorbent assay among 64 patients with CF and 31 healthy controls. The αCGRP concentration in the CF group was 62.51 ± 15.45 pg/mL, while in the control group it was 47.43 ± 8.06 pg/mL (p < 0.001). We also compared the level of αCGRP in CF patients according to the type of CFTR mutation. Homozygotes for ΔF508 had higher αCGRP levels than heterozygotes (67.9 ± 10.2 vs. 54.5 ± 18.3 pg/mL, p < 0.01). The level of this neuropeptide was statistically higher in patients with severe disease than in those with mild CF (p = 0.003) when patients were divided into three groups by spirometry results. αCGRP concentration was not correlated with age, sex, clinical parameters, and pulmonary function test results in the study participants. The results of our study suggest a significant increase in the concentration of αCGRP in the serum of patients with CF compared to the control group. This observation opens interesting possibilities for understanding the role of αCGRP in the context of CF pathophysiology. Full article

In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol’s efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment. Full article

Objective: The vast majority of gastrointestinal stromal tumors (GISTs) are driven by activating mutations in KIT, PDGFRA, or components of the succinate dehydrogenase (SDH) complex (SDHA, SDHB, SDHC, and SDHD genes). A small fraction of GISTs lack alterations in KIT, PDGFRA, and SDH. We aimed to further characterize the clinical and genomic characteristics of these so-called “triple-negative” GISTs. Methods: We extracted clinical and genomic data from patients seen at MD Anderson Cancer Center with a diagnosis of GIST and available clinical next generation sequencing data to identify “triple-negative” patients. Results: Of the 20 patients identified, 11 (55.0%) had gastric, 8 (40.0%) had small intestinal, and 1 (5.0%) had rectal primary sites. In total, 18 patients (90.0%) eventually developed recurrent or metastatic disease, and 8 of these presented with de novo metastatic disease. For the 13 patients with evaluable response to imatinib (e.g., neoadjuvant treatment or for recurrent/metastatic disease), the median PFS with imatinib was 4.4 months (range 0.5–191.8 months). Outcomes varied widely, as some patients rapidly developed progressive disease while others had more indolent disease. Regarding potential genomic drivers, four patients were found to have alterations in the RAS/RAF/MAPK pathway: two with a BRAF V600E mutation and two with NF1 loss-of-function (LOF) mutations (one deletion and one splice site mutation). In addition, we identified two with TP53 LOF mutations, one with NTRK3 fusion (ETV6-NTRK3), one with PTEN deletion, one with FGFR1 gain-of-function (GOF) mutation (K654E), one with CHEK2 LOF mutation (T367fs*), one with Aurora kinase A fusion (AURKA-CSTF1), and one with FANCA deletion. Patients had better responses with molecularly targeted therapies than with imatinib. Conclusions: Triple-negative GISTs comprise a diverse cohort with different driver mutations. Compared to KIT/PDGFRA-mutant GIST, limited benefit was observed with imatinib in triple-negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy. Full article

Stress is an important risk factor for the onset of anxiety and depression. The ability to cope with stressful events varies among different subjects, probably depending on different genetic variants, sex and previous life experiences. The Val66Met variant of Brain-Derived Neurotrophic Factor (BDNF), which impairs the activity-dependent secretion of BDNF, has been associated with increased susceptibility to the development of various neuropsychiatric disorders. Adult male and female wild-type Val/Val (BDNF^V/V) and heterozygous Val/Met (BDNF^V/M) mice were exposed to two sessions of forced swimming stress (FSS) per day for two consecutive days. The mice were behaviorally tested 1 day (short-term effect) or 11 days (long-term effect) after the last stress session. Protein and mRNA levels were measured in the hippocampus 16 days after the end of stress exposure. Stressed mice showed a higher anxiety-like phenotype compared to non-stressed mice, regardless of the sex and genotype, when analyzed following the short period of stress. In the prolonged period, anxiety-like behavior persisted only in male BDNF^V/M mice (p < 0.0001). Interestingly, recovery in male BDNF^V/V mice was accompanied by an increase in pCREB (p < 0.001) and Bdnf4 (p < 0.01) transcript and a decrease in HDAC1 (p < 0.05) and Dnmt3a (p = 0.01) in the hippocampus. Overall, our results show that male and female BDNF Val66Met knock-in mice can recover from subchronic stress in different ways. Full article

Background and Objectives: No comparative study has evaluated the inter-method agreement and reliability between Heuron AD and other clinically available brain volumetric software packages. Hence, we aimed to investigate the inter-method agreement and reliability of three clinically available brain volumetric software packages: FreeSurfer (FS), NeuroQuant^® (NQ), and Heuron AD (HAD). Materials and Methods: In this study, we retrospectively included 78 patients who underwent conventional three-dimensional (3D) T1-weighed imaging (T1WI) to evaluate their memory impairment, including 21 with normal objective cognitive function, 24 with mild cognitive impairment, and 33 with Alzheimer’s disease (AD). All 3D T1WI scans were analyzed using three different volumetric software packages. Repeated-measures analysis of variance, intraclass correlation coefficient, effect size measurements, and Bland–Altman analysis were used to evaluate the inter-method agreement and reliability. Results: The measured volumes demonstrated substantial to almost perfect agreement for most brain regions bilaterally, except for the bilateral globi pallidi. However, the volumes measured using the three software packages showed significant mean differences for most brain regions, with consistent systematic biases and wide limits of agreement in the Bland–Altman analyses. The pallidum showed the largest effect size in the comparisons between NQ and FS (5.20–6.93) and between NQ and HAD (2.01–6.17), while the cortical gray matter showed the largest effect size in the comparisons between FS and HAD (0.79–1.91). These differences and variations between the software packages were also observed in the subset analyses of 45 patients without AD and 33 patients with AD. Conclusions: Despite their favorable reliability, the software-based brain volume measurements showed significant differences and systematic biases in most regions. Thus, these volumetric measurements should be interpreted based on the type of volumetric software used, particularly for smaller structures. Moreover, users should consider the replaceability-related limitations when using these packages in real-world practice. Full article