bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanding Broad Molecular Reflex Testing in Non-Small Cell Lung Cancer to Squamous Histology
Authors: Zacharias Martin , Konjic Selma , Kratochwill Nikolaus , Absenger Gudrun , Terbuch Angelika , Jost Philipp J. , Wurm Robert , Lindenmann Jörg , Kashofer Karl , Gollowitsch Franz , Gorkiewicz Gregor , Brcic Luka
Published: February 2024

Due to the success story of biomarker-driven targeted therapy, most NSCLC guidelines agree that molecular reflex testing should be performed in all cases with non-squamous cell carcinoma (non-SCC). In contrast, testing recommendations for squamous cell carcinoma (SCC) vary considerably, specifically concerning the exclusion of patients of certain age or smoking status from molecular testing strategies. We performed a retrospective single-center study examining the value of molecular reflex testing in an unselected cohort of 316 consecutive lung SCC cases, tested by DNA- and RNA-based next-generation sequencing (NGS) at our academic institution between 2019 and 2023. Clinicopathological data from these cases were obtained from electronic medical records and correlated with sequencing results. In 21/316 (6.6%) cases, we detected an already established molecular target for an approved drug. Among these were seven cases with an EGFR mutation, seven with a KRAS G12C mutation, four with an ALK fusion, two with an EGFR fusion and one with a METex14 skipping event. All patients harboring a targetable alteration were >50 years of age and most of them had >15 pack-years, questioning restrictive molecular testing strategies. Based on our real-world data, we propose a reflex testing workflow using DNA- and RNA-based NGS that includes all newly diagnosed NSCLC cases, irrespective of histology, but also irrespective of age or smoking status.
Outcomes of Late-Line Systemic Treatment in GIST: Does Sequence Matter?
Authors: Thirasastr Prapassorn , Sutton Thomas L. , Joseph Cissimol P. , Lin Heather , Amini Behrang , Mayo Skye C. , Araujo Dejka , Benjamin Robert S. , Conley Anthony P. , Livingston John A. , Ludwig Joseph , Patel Shreyaskumar , Ratan Ravin , Ravi Vinod , Zarzour Maria A. , Nassif Haddad Elise F. , Nakazawa Michael S. , Zhou Xiao , Heinrich Michael C. , Somaiah Neeta
Published: February 2024

Ripretinib and avapritinib have demonstrated activity in the late-line treatment of gastrointestinal stomal tumors (GISTs). We investigated whether patients previously treated with ripretinib benefit from avapritinib, and vice versa. Patients diagnosed with metastatic/unresectable GIST and treated with both drugs at two institutions in 2000–2021 were included. Patients were grouped by drug sequence: ripretinib–avapritinib (RA) or avapritinib–ripretinib (AR). Radiographic response was evaluated using RECIST 1.1. Kaplan–Meier and log-rank tests were used to compare time-to-progression (TTP) and overall survival (OS). Thirty-four patients (17 per group) were identified, with a median age of 48 years. The most common primary site was the small bowel (17/34, 50%), followed by the stomach (10/34, 29.4%). Baseline characteristics and tumor mutations were not significantly different between groups. Response rates (RRs) for ripretinib were 18% for RA and 12% for AR; RRs for avapritinib were 12% for AR and 18% for RA. Median TTPs for ripretinib were 3.65 months (95%CI 2–5.95) for RA and 4.73 months (1.87–15.84) for AR. Median TTPs for avapritinib were 5.39 months (2.86–18.99) for AR and 4.11 months (1.91–11.4) for RA. Median OS rates following RA or AR initiation were 29.63 (95%CI 13.8–50.53) and 33.7 (20.03–50.57) months, respectively. Both ripretinib and avapritinib were efficacious in the late-line treatment of GIST, with no evidence that efficacy depended on sequencing.
Towards a Simplified and Cost-Effective Diagnostic Algorithm for the Surveillance of Intraductal Papillary Mucinous Neoplasms (IPMNs): Can We Save Contrast for Later?
Authors: Brandi Nicolò , Renzulli Matteo
Published: February 2024

The increased detection of pancreatic cysts in recent years has triggered extensive diagnostic investigations to clarify their potential risk of malignancy, resulting in a large number of patients undergoing numerous imaging follow-up studies for many years. Therefore, there is a growing need for optimization of the current surveillance protocol to reduce both healthcare costs and waiting lists, while still maintaining appropriate sensibility and specificity. Imaging is an essential tool for evaluating patients with intraductal papillary mucinous neoplasms (IPMNs) since it can assess several predictors for malignancy and thus guide further management recommendations. Although contrast-enhanced magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) has been widely recommended by most international guidelines, recent results support the use of unenhanced abbreviated-MRI (A-MRI) protocols as a surveillance tool in patients with IPMN. In fact, A-MRI has shown high diagnostic performance in malignant detection, with high sensitivity and specificity as well as excellent interobserver agreement. The aim of this paper is, therefore, to discuss the current available evidence on whether the implementation of an abbreviated-MRI (A-MRI) protocol for cystic pancreatic lesion surveillance could improve healthcare economics and reduce waiting lists in clinical practice without significantly reducing diagnostic accuracy.
The Gap of Health Inequalities Amongst Lung Cancer Patients of Different Socioeconomic Status: A Brief Reference to the Greek Reality
Authors: Sofianidi Amalia , Karadimou Alexandra , Charpidou Andriani , Syrigos Konstantinos N.
Published: February 2024

Lung cancer treatment and patient care are constantly improving, but it remains doubtful whether this applies equally to all socioeconomic groups. It is nowadays well established that there are socioeconomic inequalities regarding lung cancer incidence, screening, effective treatment, overall survival, and prognosis. One of the key contributing factors to low socioeconomic status is low education. Low educational level is correlated with several factors, such as smoking habits, bad lifestyle behaviors, lower paid and unhealthier occupations, polluted neighborhoods, and genetic-familial risk, that lead to increased lung cancer incidence. The disparities regarding lung cancer care are further enhanced by stigma. On this basis and inspired by the gap in health equality among the Greek population, the Greek Society of Lung Cancer initiated a campaign, “MIND THE GAP”, to help increase awareness and minimize the gap associated with lung cancer, both in Greece and across Europe. The aim of this review is to explore the gap of health inequalities regarding lung cancer incidence and prognosis between patients of different SES and its root of causality. Key pivotal actions towards bridging this gap are reviewed as well.
Tumoral C2 Regulates the Tumor Microenvironment by Increasing the Ratio of M1/M2 Macrophages and Tertiary Lymphoid Structures to Improve Prognosis in Melanoma
Authors: Zhang Gengpu , Li Shengnan , Xiao Wanyi , Zhang Chao , Li Ting , Liao Zhichao , Liu Haotian , Xing Ruwei , Yao Wei , Yang Jilong
Published: February 2024

Immunotherapy is an essential therapy for individuals with advanced melanoma. However, not all patients respond to such treatment due to individual differences. We conducted a multidimensional analysis using transcriptome data from our center, as well as publicly available databases. We found that effective nivolumab treatment led to an upregulation of C2 levels, and higher levels following treatment are indicative of a good outcome. Through bioinformatics analyses and immunofluorescence, we identified a correlation between C2 and M1 macrophages. To further investigate the role of C2 in melanoma, we constructed subcutaneous tumorigenic models in C57BL/6 mice. The tumors in the C2 overexpression group exhibited significantly smaller sizes. Flow cytometric analysis of the mouse tumors demonstrated enhanced recruitment of macrophages, particularly of the M1 subtype, in the overexpression group. Moreover, single-cell RNA sequencing analysis revealed that C2-positive tumor cells exhibited enhanced communication with immune cells. We co-cultured tumor cell supernatants with macrophages in vitro and observed the induction of M1 subtype polarization. In addition, we discovered a close correlation between C2 and tertiary lymphoid structures. C2 has been demonstrated to exert a protective effect, mediated by its ability to modulate the tumor microenvironment. C2 serves as a prognostic marker for melanoma and can be employed to monitor the efficacy of immunotherapy.
Breast Tumor Metastasis and Its Microenvironment: It Takes Both Seed and Soil to Grow a Tumor and Target It for Treatment
Authors: Bonni Shirin , Brindley David N. , Chamberlain M. Dean , Daneshvar-Baghbadorani Nima , Freywald Andrew , Hemmings Denise G. , Hombach-Klonisch Sabine , Klonisch Thomas , Raouf Afshin , Shemanko Carrie Simone , Topolnitska Diana , Visser Kaitlyn , Vizeacoumar Franco J. , Wang Edwin , Gibson Spencer B.
Published: February 2024

Metastasis remains a major challenge in treating breast cancer. Breast tumors metastasize to organ-specific locations such as the brain, lungs, and bone, but why some organs are favored over others remains unclear. Breast tumors also show heterogeneity, plasticity, and distinct microenvironments. This contributes to treatment failure and relapse. The interaction of breast cancer cells with their metastatic microenvironment has led to the concept that primary breast cancer cells act as seeds, whereas the metastatic tissue microenvironment (TME) is the soil. Improving our understanding of this interaction could lead to better treatment strategies for metastatic breast cancer. Targeted treatments for different subtypes of breast cancers have improved overall patient survival, even with metastasis. However, these targeted treatments are based upon the biology of the primary tumor and often these patients’ relapse, after therapy, with metastatic tumors. The advent of immunotherapy allowed the immune system to target metastatic tumors. Unfortunately, immunotherapy has not been as effective in metastatic breast cancer relative to other cancers with metastases, such as melanoma. This review will describe the heterogeneic nature of breast cancer cells and their microenvironments. The distinct properties of metastatic breast cancer cells and their microenvironments that allow interactions, especially in bone and brain metastasis, will also be described. Finally, we will review immunotherapy approaches to treat metastatic breast tumors and discuss future therapeutic approaches to improve treatments for metastatic breast cancer.
Estimating the Anti-Viral Performance of Photocatalytic Materials: The Correlation between Air Purification Efficiency and Severe Acute Respiratory Syndrome Coronavirus 2 Inactivation
Authors: Ochiai Tsuyoshi , Nagai Takeshi , Hamada Kengo , Tobe Tomoyuki , Aoki Daisuke , Sunada Kayano , Ishiguro Hitoshi
Published: February 2024

The coronavirus disease 2019 pandemic has increased the demand for anti-viral products. Photocatalytic materials are used to develop coatings and air purifiers that inactivate severe acute respiratory syndrome coronavirus 2. However, the methods for evaluating the anti-viral performance of photocatalytic materials are time-consuming. To address this problem, herein, we propose a screening test for the anti-viral performance of photocatalytic materials based on the ‘acetaldehyde decomposition test’—an air purification efficiency test used to evaluate the decomposition performance of photocatalytic materials. This test is suitable for screening multiple samples and conditions in a short period. The temporal variation in the acetaldehyde concentration was approximated using an exponential function, similar to the temporal variation in the viral infection values. Thereafter, the slope of the regression line for the acetaldehyde concentration over time was used as an indicator in the screening tests. When the anti-viral performance and acetaldehyde decomposition tests were conducted on the same photocatalytic material, a correlation was observed between the slopes of the regression lines. Overall, the proposed screening test shows good potential for evaluating the anti-viral performance of photocatalytic materials.
Downregulation of Ribosomal Protein Genes Is Revealed in a Model of Rat Hippocampal Neuronal Culture Activation with GABA(A)R/GlyRa2 Antagonist Picrotoxin
Authors: Beletskiy Alexander , Zolotar Anastasia , Fortygina Polina , Chesnokova Ekaterina , Uroshlev Leonid , Balaban Pavel , Kolosov Peter
Published: February 2024

Long-read transcriptome sequencing provides us with a convenient tool for the thorough study of biological processes such as neuronal plasticity. Here, we aimed to perform transcriptional profiling of rat hippocampal primary neuron cultures after stimulation with picrotoxin (PTX) to further understand molecular mechanisms of neuronal activation. To overcome the limitations of short-read RNA-Seq approaches, we performed an Oxford Nanopore Technologies MinION-based long-read sequencing and transcriptome assembly of rat primary hippocampal culture mRNA at three time points after the PTX activation. We used a specific approach to exclude uncapped mRNAs during sample preparation. Overall, we found 23,652 novel transcripts in comparison to reference annotations, out of which ~6000 were entirely novel and mostly transposon-derived loci. Analysis of differentially expressed genes (DEG) showed that 3046 genes were differentially expressed, of which 2037 were upregulated and 1009 were downregulated at 30 min after the PTX application, with only 446 and 13 genes differentially expressed at 1 h and 5 h time points, respectively. Most notably, multiple genes encoding ribosomal proteins, with a high basal expression level, were downregulated after 30 min incubation with PTX; we suggest that this indicates redistribution of transcriptional resources towards activity-induced genes. Novel loci and isoforms observed in this study may help us further understand the functional mRNA repertoire in neuronal plasticity processes. Together with other NGS techniques, differential gene expression analysis of sequencing data obtained using MinION platform might provide a simple method to optimize further study of neuronal plasticity.
Traumatic Brain Injury Recovery with Photobiomodulation: Cellular Mechanisms, Clinical Evidence, and Future Potential
Authors: Lim Lew
Published: February 2024

Traumatic Brain Injury (TBI) remains a significant global health challenge, lacking effective pharmacological treatments. This shortcoming is attributed to TBI’s heterogeneous and complex pathophysiology, which includes axonal damage, mitochondrial dysfunction, oxidative stress, and persistent neuroinflammation. The objective of this study is to analyze transcranial photobiomodulation (PBM), which employs specific red to near-infrared light wavelengths to modulate brain functions, as a promising therapy to address TBI’s complex pathophysiology in a single intervention. This study reviews the feasibility of this therapy, firstly by synthesizing PBM’s cellular mechanisms with each identified TBI’s pathophysiological aspect. The outcomes in human clinical studies are then reviewed. The findings support PBM’s potential for treating TBI, notwithstanding variations in parameters such as wavelength, power density, dose, light source positioning, and pulse frequencies. Emerging data indicate that each of these parameters plays a role in the outcomes. Additionally, new research into PBM’s effects on the electrical properties and polymerization dynamics of neuronal microstructures, like microtubules and tubulins, provides insights for future parameter optimization. In summary, transcranial PBM represents a multifaceted therapeutic intervention for TBI with vast potential which may be fulfilled by optimizing the parameters. Future research should investigate optimizing these parameters, which is possible by incorporating artificial intelligence.
Cancer Drug Resistance: Targeting Proliferation or Programmed Cell Death
Authors: Sazonova Elena V. , Yapryntseva Maria A. , Pervushin Nikolay V. , Tsvetcov Roman I. , Zhivotovsky Boris , Kopeina Gelina S.
Published: February 2024

The development of resistance to chemotherapy is one of the main problems for effective cancer treatment. Drug resistance may result from disturbances in two important physiological processes—cell proliferation and cell death. Importantly, both processes characterize alterations in cell metabolism, the level of which is often measured using MTT/MTS assays. To examine resistance to chemotherapy, different cancer cell lines are usually used for the in vitro modulation of developing resistance. However, after the creation of resistant cell lines, researchers often have difficulty in starting investigations of the mechanisms of insensitivity. In the first stage, researchers should address the question of whether the drug resistance results from a depression of cell proliferation or an inhibition of cell death. To simplify the choice of research strategy, we have suggested a combination of different approaches which reveal the actual mechanism. This combination includes rapid and high-throughput methods such as the MTS test, the LIVE/DEAD assay, real-time cell metabolic analysis, and Western blotting. To create chemoresistant tumor cells, we used four different cancer cell lines of various origins and utilized the most clinically relevant pulse-selection approach. Applying a set of methodological approaches, we demonstrated that three of them were more capable of modulating proliferation to avoid the cytostatic effects of anti-cancer drugs. At the same time, one of the studied cell lines developed resistance to cell death, overcoming the cytotoxic action.
Cultivating Resilience in Chaos: Localisation as a Mechanism for Sustainability and Inner Development in Syria’s Humanitarian Crisis
Authors: Rose Jo , Elbaaly Eslam
Published: February 2024

This article explores localisation in humanitarian settings as an example of sustainability and inner development. Through a case study from Syria, we discuss how localisation and remote management can lead to the mutual flourishing of individuals, communities and planetary health in the most challenging settings. Through localisation, we can rethink and reframe humanitarianism and integrate sustainability and personal development. Learning from these collaborations that highlight the importance of trust and interpersonal relations, the humanitarian and global health communities can reflect on how local individuals and communities can be further supported in their personal development and the sustainability of interventions that promote planetary health.
Decline in Processing Speed Tells Only Half the Story: Developmental Delay in Children Living with Sickle Cell Disease
Authors: Walker Elise Jade , Kirkham Fenella Jane , Hood Anna Marie
Published: February 2024

Children with sickle cell disease (SCD) may experience cognitive difficulties, including slowed processing speed. Thus, we investigated if processing speed changes over time. From 1992–2001, 103 participants with SCD aged 3–16 years (n ≤ 8.99 = 45; n ≥ 9.00 = 58) completed cognitive assessments. MRI was available for 54 participants. Between 1992–2002, 58 participants consented to one or two further assessments. A repeated measures regression using linear mixed-effects modelling determined longitudinal changes in processing speed index (PSI), examining the interaction between age (continuous variable) and timepoint (i.e., assessment 1 or 3) and controlling for MRI infarct status (i.e., no infarct, silent infarct, or stroke). Those aged ≤8.99 and ≥9.00 at first assessment experienced PSI decline. Declines were most prominent for the processing speed coding subtest, with a significant interaction between timepoint and age, t(31) = 2.64, p = 0.01. This decline may reflect a developmental delay, likely due to disease progression, with slower improvements in processing speed. Although there have been significant improvements in SCD treatments, mostly in high-income countries, processing speed still remains a target; thus, incorporating clinical monitoring of processing speed may help identify delay and allow for early intervention.
Fetal and Infant Effects of Maternal Opioid Use during Pregnancy: A Literature Review including Clinical, Toxicological, Pharmacogenomic, and Epigenetic Aspects for Forensic Evaluation
Authors: Giovannini Elena , Bonasoni Maria Paola , Pascali Jennifer Paola , Bini Carla , Pelletti Guido , Gualandi Alberto , Dal Lago Giovanni , Mercati Andrea , Mariotti Beatrice , Pasini Giulia Paola , Poll Iarina Alexandra , Fais Paolo
Published: February 2024

The two primary classes of opioid substances are morphine and its synthetic derivative, heroin. Opioids can cross the placental barrier, reaching fetal circulation. Therefore, at any gestational age, the fetus is highly exposed to pharmacologically active opioid metabolites and their associated adverse effects. This review aimed to investigate all the studies reported in a timeframe of forty years about prenatal and postnatal outcomes of opioid exposition during pregnancy. Clinical and toxicological aspects, as well as pharmacogenetic and epigenetic research focusing on fetal and infant effects of opioid use during pregnancy together with their medico-legal implications are exposed and discussed.
Infusion-Related Reactions Subsequent to Avelumab, Durvalumab, and Atezolizumab Administration: A Retrospective Observational Study
Authors: Hata Keiko , Nakamura Keina , Maeda Shinichiro , Maeda Makiko , Fujio Yasushi , Hirobe Sachiko
Published: February 2024

Background: Avelumab, durvalumab, and atezolizumab are anti-programmed death-ligand 1 (PD-L1) antibodies approved for clinical application in Japan. Despite targeting the same molecule, avelumab elicits a different frequency of infusion-related reactions (IRRs) compared with durvalumab and atezolizumab, leading to differences in premedication recommendations. This study aimed to collect information to verify the relationship during IRRs and the characteristics of antibody molecules, by investigating the frequency of IRRs caused by three types of antibodies and the actual status of prophylactic measures. Methods: This single-center, retrospective observational study collected the medical records of 73 patients who received avelumab, durvalumab, or atezolizumab at Osaka University Hospital. Results: The frequency of IRRs was 50.0% (12/24) for avelumab, 31.0% (8/27) for durvalumab, and 18.2% (4/22) for atezolizumab. The IRRs were grade 2 in seven patients and grade 1 in five patients treated with avelumab, grade 2 in six patients and grade 1 in two patients treated with durvalumab, and grade 1 in all patients treated with atezolizumab. Among patients in whom symptoms were observed during the first administration, measures were taken to prevent IRRs for the second administration, but cases were confirmed in which symptoms reappeared, especially in patients who received durvalumab. Conclusion: Our findings indicate that the frequency of IRRs due to anti-PD-L1 antibodies is higher than that previously reported in clinical trials and different modifications in antibody molecules may affect the difference in IRR frequency.
Interfacial Stability between High-Entropy (La0.2Yb0.2Sm0.2Eu0.2Gd0.2)2Zr2O7 and Yttria-Stabilized Zirconia for Advanced Thermal Barrier Coating Applications
Authors: Yang Guojie , Han Chenbing , Chen Ying , Guo Fangwei , Lu Jie , Zhou Ming , Luo Lirong , Zhao Xiaofeng
Published: February 2024

(La0.2Yb0.2Sm0.2Eu0.2Gd0.2)2Zr2O7 (HEZ) has shown considerable promise as a novel thermal barrier coating material for temperatures exceeding 1300 °C. This study systematically investigates the interfacial stability of (La0.2Yb0.2Sm0.2Eu0.2Gd0.2)2Zr2O7 with yttria-stabilized zirconia (YSZ), which is of paramount importance for its application in double-layer thermal barrier coatings. Our findings highlight that rare earth elements with a smaller radius diffuse more easily into the YSZ lattice, resulting in a broader diffusion zone. Simultaneously, the incorporation of rare earth elements into the YSZ lattice inhibits tetragonal-to-monoclinic phase transformation. Compared to La2Zr2O7/YSZ, HEZ/YSZ demonstrates superior high-temperature stability, which could be attributed to the higher fracture toughness and lower thermal expansion coefficient of HEZ, the absence of t-m transformation and the formation of a continuous gradient diffusion layer that minimizes interface stress. This study offers a practical strategy for designing materials for durable double-layer thermal barrier coating systems.
Interaction of Perfumes with Cytochrome P-450 19
Authors: Drejslarová Iva , Ječmen Tomáš , Hodek Petr
Published: February 2024

Cytochrome P450 (CYP) enzymes play a key role in the metabolism of foreign compounds and in the biosynthesis and catabolism of endogenous substances, including hormones. The activity of these enzymes can be affected by various xenobiotics, such as pollutants, food constituents, pharmaceuticals, and cosmetic products, which can disrupt the endocrine system by interfering with steroidogenic CYPs. CYP19, also known as aromatase, is a crucial enzyme for testosterone conversion into 17β-estradiol, which is the final step in estrogen biosynthesis. Endocrine disruptors have the potential to inhibit CYP19 activity, leading to an imbalance in estrogen levels in the body. This imbalance can impair reproduction and cause osteoporosis, atherosclerosis, dementia, and some types of cancer. The aim of this study was to assess the effect of commercially available perfumes on testosterone aromatization to 17β-estradiol. For this purpose, we used high-performance liquid chromatography (HPLC) with UV detection and HPLC coupled with mass spectrometry (MS) to examine CYP19 activity with and without perfume. The results showed that all perfumes tested (in a 300-fold dilution) had an inhibitory effect on this enzyme-catalyzed reaction, particularly the Montale® fragrance, ‘Intense Roses Musk’, which decreased 17β-estradiol production by 88% in comparison with the control. Upon exposure to UV light, the inhibitory effect of this perfume did not decrease. But exposure to UV light significantly increased the inhibitory capacity of another perfume with a weak baseline inhibitory effect. To ascertain whether this inhibition was caused by CYP19 interactions with perfumes, we measured the catalytic activity of NADPH:cytochrome P450 oxidoreductase (CYPOR), the CYP reaction partner, with one selected perfume, ‘Intense Roses Musk’ by Montale®, and found no significant CYPOR inhibition. Accordingly, the decrease in testosterone conversion into 17β-estradiol caused by this perfume derives solely from CYP19. Combined, our findings highlight the importance of testing perfumes rather than single ingredients to determine their potential for adverse effects and to ensure consumer safety because their mixtures can interfere with a key enzyme of estrogen biosynthesis.
Stress-Based Model for Calculating the Opening Angle of Notch Cracks in a Magnesium Alloy under Multiaxial Fatigue
Authors: Videira Henrique , Anes Vitor , Reis Luis
Published: February 2024

This paper presents a model to calculate the opening angle of crack initiation in notched fractures subjected to multiaxial loading. To validate the proposed model, a study was performed on polished AZ31B-F magnesium alloy specimens under multiaxial high-cycle fatigue loading. The specimens exhibited a notch in the smaller cross-sectional area, which was created with a special drilling jig to promote the formation of fatigue cracks in this localized area of the specimen. The load paths used in the experiments and numerical analyses were proportional and non-proportional, resulting in different stress states in the crack front opening, which were determined by finite element analysis to validate the proposed model. To obtain more accurate numerical results for these estimates, these finite element analyses were performed using the nonlinear Chaboche plasticity model of ABAQUS® 2021 software. A sensitivity analysis was also performed to determine which load component—axial or torsional—has a greater influence on the fatigue strength and contributes significantly to the crack opening process. The results show that the type of load path and the stress level of each load component—axial and torsional—has a strong influence on the opening angle of the notch crack and the fatigue lifetime of the specimen. This result is confirmed not only by the experimentally determined fatigue strength, but also by a fractographic analysis performed on the surface of the specimens for both load paths. Moreover, the results show an acceptable correlation between the experimental results and the estimates obtained with the proposed model and the stresses obtained with the finite element analysis.
Effect of Al-Cu-Fe Quasicrystal Particles on the Reinforcement of a Polymer–Matrix Composite: From Surface to Mechanical Properties
Authors: Kušter Monika , Samardžija Zoran , Komelj Matej , Huskić Miroslav , Bek Marko , Pierson Gaël , Kouitat-Njiwa Richard , Dubois Jean-Marie , Šturm Sašo
Published: February 2024

We examined the effect of Al59Cu25Fe13B3 (at.%) quasicrystalline (QC) reinforcement particles on the mechanical and surface properties of a polymer-matrix composite by applying a technical polymer polyphthalamide (PPA). The observed increase in the tensile Young’s modulus ranged from 1810 MPa for the pure polymer to 4114 MPa for the composite with a QC filling of 35 vol.%. The elongation at fracture decreased with the filling fraction, being equal to 16.9% for a pure polymer and dropping to 4.8% for the composite with a QC filling of 35 vol.%. The same trend was noticeable with flexural Young’s modulus, which ranged from 100 MPa for a pure polymer to 125.5 MPa for the composite with 35 vol.% of QC. It was found that the increase in the mechanical strength led to a simultaneous increase of brittleness, which was reflected in a decrease of the impact strength for a pure polymer from 98.5 kJ/m2 to 42.4 kJ/m2 for composites with a QC filling of 35 vol.%. In contrast, when filled with 5 vol.% of QC, the impact strength increased by 8%. The friction coefficient against 100C6 steel dropped from 0.15 for pure PPA down to 0.10 for 5 vol.% of the QC filling, followed by an increase to 0.26 for further QC fillings up to 35 vol.%. Interestingly, a local minimum of friction was achieved at filling factors between 5 to 20 vol.% of QC. Independently, a clear surfenergy minimum was also found for the composite material with 20 vol.% of QC filling associated with a net drop in the polar component of the surfenergy. Surfenergy refers to the surface energy related to the top of the oxide layer under ambient conditions. We hypothesise that this is related to the percolation threshold at about 13 vol.% QC, reflected in the observed behaviour of both the friction coefficient and surfenergy. For the pure QC annealed in air for 1 h at 500 °C significant wear tracks were observed accompanied by a wear debris formation. On the other hand, a pure polymer exhibited slightly visible wear tracks with no apparent debris formation, and for the composites with different QC filling factors, the wear traces were barely visible with negligible debris formation.
And Yet They Differ: Reconsiderations of Diversity within Dactylochelifer latreillii (Arachnida: Pseudoscorpiones)
Authors: Muster Christoph , Korba Jan , Bogusch Petr , Heneberg Petr , Šťáhlavský František
Published: February 2024

Morphological stasis is a widespread characteristic of pseudoscorpions, suggesting that much cryptic diversity remains unexplored. Here, we revise the polytypic species Dactylochelifer latreillii in the framework of an integrative taxonomic approach, using DNA barcoding, multivariate ratio analysis, geometric morphometry of the male foretarsus, and genitalic morphology. The pattern of mitochondrial variation suggests three species-level entities in central Europe, which widely overlap in morphospace, but differentiate in the structure of the female genitalia, and by their ecology. Dactylochelifer latreillii (Leach) is a halobiont species, occurring exclusively in coastal habitats and in Pannonian salt steppes, and D. l. septentrionalis Beier syn. nov. is a junior synonym of the nominate species. Dactylochelifer degeerii (C. L. Koch) stat. rev. is the oldest available name for an inland species that has long been mistaken for the nominotypical subspecies of D. latreillii. New habitat information suggests a preference for higher shrub vegetation. Dactylochelifer ninnii (Canestrinii) stat. rev. is a halophilic Mediterranean species that extends to the northern limits of the Pannonian basin. The distinctiveness of the Mediterranean “form” was recognized by early naturalists in the 19th century, but was ignored by later authorities in the field.
A Case of Castleman’s Disease with a Marked Infiltration of IgG4-Positive Cells in the Renal Interstitium
Authors: Sawada Erika , Shioda Yuya , Ogawa Kohki , Iwashita Takatsugu , Ono Yuko , Hasegawa Hajime , Maeshima Akito
Published: February 2024

Multicentric Castleman’s disease (MCD) is a benign lymphoproliferative disorder with heterogenous clinical symptoms, and involves systemic organs in addition to lymph nodes. Herein, we present the case of a 55-year-old man with MCD characterized by an extensive infiltration of IgG4+ plasma cells in the kidneys. The patient presented to our hospital with a high fever and diarrhea. On admission, laboratory analysis revealed anemia, renal dysfunction (eGFR 30 mL/min/1.73 m2), polyclonal gammopathy (IgG 7130 mg/dL), elevated serum IgG4 level (2130 mg/dL), and increased C-reactive protein (8.0 mg/dL). An enlargement of lymph nodes in the axillary, mediastinal, para-aortic, and inguinal regions was observed on abdominal computed tomography. Axillary lymph node biopsy revealed interfollicular expansion due to dense plasma cell infiltration. Renal biopsy demonstrated significant plasma cell infiltration into the tubulointerstitium. Immunohistochemical analysis showed a 40% IgG4-positive/IgG-positive plasma cell ratio, meeting the diagnostic criteria for an IgG4-related disease. Amyloid A deposition was observed along vessel walls, and immunofluorescence analysis indicated granular positivity of IgG and C3 along the glomerular capillary wall. Elevated levels of interleukin-6 (21 pg/mL) and vascular endothelial growth factor (VEGF; 1210 pg/mL) were noted. Based on these findings, and the histological finding of the lymph node biopsy, idiopathic MCD was diagnosed. Corticosteroid monotherapy was only partially effective. Subsequently, tocilizumab administration was initiated, leading to sustained remission, even after discontinuation of prednisolone. Due to the diverse responses to steroid therapy and the varying prognoses observed in MCD and IgG4-related disease, it is essential to carefully diagnose MCD by thoroughly assessing the organ distribution of the disease, its response to steroid therapy, and any additional pathological findings.
Reply to Otiti-Sengeri et al. Chorioretinitis among Immigrant and Travellers. Comment on “Mansour et al. Presumed Onchocerciasis Chorioretinitis Spilling over into North America, Europe and Middle East. Diagnostics 2023, 13, 3626”
Authors: Mansour Ahmad , Rodriguez Linnet , Mansour Hana , Yehia Madeleine , Battaglia Parodi Maurizio
Published: February 2024

The comments by Otiti et al [...]
Advances in Transepithelial Photorefractive Keratectomy versus Laser-Assisted In Situ Keratomileusis
Authors: Curcă Paul Filip , Tătaru Cătălina Ioana , Sima George , Burcea Marian , Tătaru Călin Petru
Published: February 2024

(1) Background: Laser-assisted refractive surgery is a safe and effective surgical correction of refractive error. For most patients, both the newer Trans-PRK and the established LASIK technique can produce the required surgical correction, sparking the question of which technique should be opted for. (2) Methods: The study prospectively evaluated 121 patients (230 eyes) for at least one month postoperatively; 66 patients (126 eyes) and 45 patients (85 eyes) returned for 6 months and 1 year follow-up. (3) Results: No statistical difference was recorded at 1 week or 1 month post-operation. At 6 months, a difference was found for spherical diopters (Trans-PRK −0.0476 ± 0.7012 versus FS-LASIK +0.425 ± 0.874, p = 0.004) and spherical equivalent (Trans-PRK −0.1994 ± 0.0294 versus FS-LASIK +0.225 ± 0.646, p = 0.025) but not for CYL D (Trans-PRK −0.3036 ± 0.5251 versus FS-LASIK −0.4 ± 0.820, p = 0.499). Uncorrected visual acuity was better for Trans-PRK 6 months post-operation (UCVA logMAR 0.02523 versus 0.0768 logMAR; p = 0.015 logMAR). At 1-year, Trans-PRK was favored for spherical diopters (Trans-PRK −0.0294 ± 0.6493 versus FS-LASIK +0.646 ± 0.909, p < 0.001) and spherical equivalent (Trans-PRK −0.218 ± 0.784 versus FS-LASIK 0.372 ± 1.08, p = 0.007). Overall speed in visual recovery, variance of results and surgically induced astigmatism were in favor of Trans-PRK. (4) Conclusions: The study reported improvements for Trans-PRK patients, with both techniques found to be safe and effective.
Evaluation of Pulmonary Nodules by Radiologists vs. Radiomics in Stand-Alone and Complementary CT and MRI
Authors: Tietz Eric , Müller-Franzes Gustav , Zimmermann Markus , Kuhl Christiane Katharina , Keil Sebastian , Nebelung Sven , Truhn Daniel
Published: February 2024

Increased attention has been given to MRI in radiation-free screening for malignant nodules in recent years. Our objective was to compare the performance of human readers and radiomic feature analysis based on stand-alone and complementary CT and MRI imaging in classifying pulmonary nodules. This single-center study comprises patients with CT findings of pulmonary nodules who underwent additional lung MRI and whose nodules were classified as benign/malignant by resection. For radiomic features analysis, 2D segmentation was performed for each lung nodule on axial CT, T2-weighted (T2w), and diffusion (DWI) images. The 105 extracted features were reduced by iterative backward selection. The performance of radiomics and human readers was compared by calculating accuracy with Clopper–Pearson confidence intervals. Fifty patients (mean age 63 +/− 10 years) with 66 pulmonary nodules (40 malignant) were evaluated. ACC values for radiomic features analysis vs. radiologists based on CT alone (0.68; 95%CI: 0.56, 0.79 vs. 0.59; 95%CI: 0.46, 0.71), T2w alone (0.65; 95%CI: 0.52, 0.77 vs. 0.68; 95%CI: 0.54, 0.78), DWI alone (0.61; 95%CI:0.48, 0.72 vs. 0.73; 95%CI: 0.60, 0.83), combined T2w/DWI (0.73; 95%CI: 0.60, 0.83 vs. 0.70; 95%CI: 0.57, 0.80), and combined CT/T2w/DWI (0.83; 95%CI: 0.72, 0.91 vs. 0.64; 95%CI: 0.51, 0.75) were calculated. This study is the first to show that by combining quantitative image information from CT, T2w, and DWI datasets, pulmonary nodule assessment through radiomics analysis is superior to using one modality alone, even exceeding human readers’ performance.
The Modified Ultrasound-Assisted Method: A Study of the Correlation between Magnetic Resonance Imaging and the Ultrasound-Assisted Evaluation of the Critical Shoulder Angle
Authors: Schamberger Christian T. , Grossner Tobias , Fischer Christian , Findeisen Sebastian , Ferbert Thomas , Suda Arnold J. , Schmidmaier Gerhard , Stein Stephan
Published: February 2024

Background: An increased or decreased critical shoulder angle (CSA) is a known risk factor for osteoarthritis, lesions, and re-ruptures in the rotator cuff. A CSA greater than 35° correlates with degenerative rotator cuff tears, while a CSA of less than 30° correlates with osteoarthritis in the glenohumeral joint. The diagnostic gold standard for its determination is X-ray or MRI. Objectives: The primary objective of this research was to assess the viability of utilizing sonography imaging as a diagnostic tool to determine the modified critical shoulder angle (mCSA). This study aimed to investigate the feasibility and effectiveness of sonographic techniques in accurately diagnosing CSA compared to MRI. Study Design and Methods: A cohort study was carried out (level of evidence 3). The CSA (MRI) and the mCSA (ultrasound) were assessed retrospectively by two independent board-certified investigators in 109 patients with shoulder pain by MRI and musculoskeletal sonography. The CSA in the MRI dataset was determined using routine protocols and then compared to the values assessed using the modified sonography-assisted method (mCSA). Both results were analyzed with linear regression to determine a possible correlation. All investigations were performed by a DEGUM (German Society for Medical Ultrasound)-certified specialist in musculoskeletal sonography. Results: A total of 112 patients were included in this study, namely 40 female patients and 72 male patients with a mean age of 54.7 years at the time of the investigation. The mean CSA in MRI was 31.5° ± 3.899, and the mCSA in sonography was 30.1° ± 4.753. The inter- and intraobserver reliability for the CSA was factual with values of 0.993 and 0.967. The inter- and intraobserver reliability for mCSA was factual as well, with values of 0.989 and 0.948. The ANOVA analysis did not reveal a significant difference between the CSA and the mCSA values, and linear regression determined the R2 value to be 0.358 with p < 0.05. Conclusions: Diagnosing the mCSA using sonography is a safe and valid method. No statistically significant differences between the results in MRI and sonography could be seen. Although this is a retrospective, single-center study including only Caucasian mid-Europeans, and with the known limitations of ultrasound imaging, it nevertheless shows that sonography can be used as a simple, cheap, and fast technique to assess a modified CSA, which shows very good correlation with the standard CSA without losing the diagnostic quality.
Phase Diagram of Nuclear Pastas in Neutron Star Crusts
Authors: Muñoz Jorge A. , López Jorge A.
Published: February 2024

Two neural networks were trained to predict, respectively, the Euler characteristic and the curvature of nuclear pastas in neutron star crust conditions generated by molecular dynamics simulations of neutron star matter with 0.1 < x < 0.5, 0.040 fm−3 < ρ < 0.085 fm−3 (0.68 × 1014 g/cm3 < ρ < 1.43 × 1014 g/cm3), and 0.2 MeV < T < 4.0 MeV, where x is proton content, the density is ρ, and the temperature is T. The predictions of the two networks were combined to determine the nuclear pasta phase that is thermodynamically stable at a given x, ρ, and T, and a three-dimensional phase diagram that extrapolated slightly the regions of existing molecular dynamics data was computed. The jungle gym and anti-jungle gym structures are prevalent at high temperature and low density, while the anti-jungle gym and anti-gnocchi structures dominate at high temperature and high density. A diversity of structures exist at low temperatures and intermediate density and proton content. The trained models used in this work are open access and available at a public repository to promote comparison to pastas obtained with other models.
Vulnerability Analysis Method Based on Network and Copula Entropy
Authors: Chen Mengyuan , Liu Jilan , Zhang Ning , Zheng Yichao
Published: February 2024

With the deepening of the diversification and openness of financial systems, financial vulnerability, as an endogenous attribute of financial systems, becomes an important measurement of financial security. Based on a network analysis, we introduce a network curvature indicator improved by Copula entropy as an innovative metric of financial vulnerability. Compared with the previous network curvature analysis method, the CE-based curvature proposed in this paper can measure market vulnerability and systematic risk with significant advantages.
Burn Wound Care Strategies for the Battlefield and Austere Settings
Authors: Shingleton Sarah , Folwell Jared , Jones Ian , Gleason Michael , Williams Alicia
Published: February 2024

Burns are commonly encountered in the battlefield environment; however, the availability of burn expertise and specialized supplies is variable. Initial burn care should remain focused on cooling the burn, preventing hypothermia, basic wound cleansing, and evacuation. Key ongoing burn wound management principles include wound debridement, accurate burn size and depth estimation, wound care, ongoing wound evaluation, and treatment of suspected Gram-negative wound infection. Operative management should be limited to urgent procedures, and definitive burn management should be performed only after evacuation to a higher level of care. Flexibility, creativity, and the ability to adapt care to the tactical environment are key to the successful management of burn injuries in battlefield and austere settings.
MeMPA: A Memory Mapped M-SIMD Co-Processor to Cope with the Memory Wall Issue
Authors: Guastamacchia Angela , Coluccio Andrea , Riente Fabrizio , Turvani Giovanna , Graziano Mariagrazia , Zamboni Maurizio , Vacca Marco
Published: February 2024

The amazing development of transistor technology has been the main driving force behind modern electronics. Over time, this process has slowed down introducing performance bottlenecks in data-intensive applications. A main cause is the classical von Neumann architecture, which entails constant data exchanges between processing units and data memory, wasting time and power. As a possible alternative, the Beyond von Neumann approach is now rapidly spreading. Although architectures following this paradigm vary a lot in layout and functioning, they all share the same principle: bringing computing elements as near as possible to memory while inserting customized processing elements, able to elaborate more data. Thus, power and time are saved through parallel execution and usage of processing components with local memory elements, optimized for running data-intensive algorithms. Here, a new memory-mapped co-processor (MeMPA) is presented to boost systems performance. MeMPA relies on a programmable matrix of fully interconnected processing blocks, each provided with memory elements, following the Multiple-Single Instruction Multiple Data model. Specifically, MeMPA can perform up to three different instructions, each on different data blocks, concurrently. Hence, MeMPA efficiently processes data-crunching algorithms, achieving energy and time savings up to 81.2% and 68.9%, respectively, compared with a RISC-V-based system.