bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes
Authors: Ribeiro Nádia , Bulut Ipek , Sergi Baris , Pósa Vivien , Spengler Gabriella , Sciortino Giuseppe , André Vânia , Ferreira Liliana P. , Biver Tarita , Ugone Valeria , Garribba Eugenio , Costa-Pessoa João , Enyedy Éva A. , Acilan Ceyda , Correia Isabel 
Published: March 2023

We report the synthesis and characterization of a group of benzoylhydrazones (Ln) derived from 2-carbaldehyde-8-hydroxyquinoline and benzylhydrazides containing distinct para substituents (R = H, Cl, F, CH3, OCH3, OH and NH2, for L1-7, respectively; in L8 isonicotinohydrazide was used instead of benzylhydrazide). Cu(II) complexes were prepared by reaction of each benzoylhydrazone with Cu(II) acetate. All compounds were characterized by elemental analysis and mass spectrometry as well as by FTIR, UV-visible absorption, NMR or electron paramagnetic resonance spectroscopies. Complexes isolated in the solid state (1–8) are either formulated as [Cu(HL)acetate] (with L1 and L4) or as [Cu(Ln)]3 (n = 2, 3, 5, 6, 7 and 8). Single crystal X-ray diffraction studies were done for L5 and [Cu(L5)]3, confirming the trinuclear formulation of several complexes. Proton dissociation constants, lipophilicity and solubility were determined for all free ligands by UV-Vis spectrophotometry in 30% (v/v) DMSO/H2O. Formation constants were determined for [Cu(LH)], [Cu(L)] and [Cu(LH−1)] for L = L1, L5 and L6, and also [Cu(LH−2)] for L = L6, and binding modes are proposed, [Cu(L)] predominating at physiological pH. The redox properties of complexes formed with L1, L5 and L6 are investigated by cyclic voltammetry; the formal redox potentials fall in the range of +377 to +395 mV vs. NHE. The binding of the Cu(II)-complexes to bovine serum albumin was evaluated by fluorescence spectroscopy, showing moderate-to-strong interaction and suggesting formation of a ground state complex. The interaction of L1, L3, L5 and L7, and of the corresponding complexes with calf thymus DNA was evaluated by thermal denaturation. The antiproliferative activity of all compounds was evaluated in malignant melanoma (A-375) and lung (A-549) cancer cells. The complexes show higher activity than the corresponding free ligand, and most complexes are more active than cisplatin. Compounds 1, 3, 5, and 8 were selected for additional studies: while these complexes induce reactive oxygen species and double-strand breaks in both cancer cells, their ability to induce cell-death by apoptosis varies. Within the set of compounds tested, 8 emerges as the most promising one, presenting low IC50 values, and high induction of oxidative stress and DNA damage, which eventually lead to high rates of apoptosis.
Contribution of GalU to biofilm formation, motility, antibiotic and serum resistance, and pathogenicity of Salmonella Typhimurium
Authors: Guo Lili , Dai Huilin , Feng Saixiang , Zhao Yongda 
Published: March 2023

IntroductionSalmonella Typhimurium is the leading cause of foodborne illnesses in China, resulting in major epidemics and economic losses in recent years. Uridine diphosphate–glucose pyrophosphorylase galU plays an important role in thebiosynthesis of the bacterial envelope. Herein, we evaluated the role of galU in S. Typhimurium infection in chicken. MethodsA galU gene mutant was successfully constructed by red homologous recombination technology, and biological characteristics were studied.ResultsThe galU mutant strain had a rough phenotype;was defective in biofilm formation, autoagglutination, and motility; exhibited greater sensitivity to most antibiotics, serum, and egg albumen; and had lowercapacity for adhesion to chicken embryo fibroblasts cell line (DF-1). The galU mutant showed dramatically attenuated pathogenicity in chicken embryos (100,000-fold), BALB/c mice (420-fold), and chicks (100-fold).DiscussionThe results imply that galU is an important virulence factor in the pathogenicity of S. Typhimurium, and it may serve a target for the development of veterinary drugs, providing a theoretical basis for the prevention and control of S. Typhimurium.
Let's go to the Alien Zoo: Introducing an experimental framework to study usability of counterfactual explanations for machine learning
Authors: Kuhl Ulrike , Artelt André , Hammer Barbara 
Published: March 2023

IntroductionTo foster usefulness and accountability of machine learning (ML), it is essential to explain a model's decisions in addition to evaluating its performance. Accordingly, the field of explainable artificial intelligence (XAI) has resurfaced as a topic of active research, offering approaches to address the “how” and “why” of automated decision-making. Within this domain, counterfactual explanations (CFEs) have gained considerable traction as a psychologically grounded approach to generate post-hoc explanations. To do so, CFEs highlight what changes to a model's input would have changed its prediction in a particular way. However, despite the introduction of numerous CFE approaches, their usability has yet to be thoroughly validated at the human level.MethodsTo advance the field of XAI, we introduce the Alien Zoo, an engaging, web-based and game-inspired experimental framework. The Alien Zoo provides the means to evaluate usability of CFEs for gaining new knowledge from an automated system, targeting novice users in a domain-general context. As a proof of concept, we demonstrate the practical efficacy and feasibility of this approach in a user study.ResultsOur results suggest the efficacy of the Alien Zoo framework for empirically investigating aspects of counterfactual explanations in a game-type scenario and a low-knowledge domain. The proof of concept study reveals that users benefit from receiving CFEs compared to no explanation, both in terms of objective performance in the proposed iterative learning task, and subjective usability.DiscussionWith this work, we aim to equip research groups and practitioners with the means to easily run controlled and well-powered user studies to complement their otherwise often more technology-oriented work. Thus, in the interest of reproducible research, we provide the entire code, together with the underlying models and user data: https://github.com/ukuhl/IntroAlienZoo.
Genomic analysis of a novel pathogenic variant in the gene LMNA associated with cardiac laminopathies found in Ecuadorian siblings: A case report
Authors: Guevara-Ramírez Patricia , Cadena-Ullauri Santiago , Ibarra-Castillo Rita , Laso-Bayas José Luis , Paz-Cruz Elius , Tamayo-Trujillo Rafael , Ruiz-Pozo Viviana A. , Doménech Nieves , Ibarra-Rodríguez Adriana Alexandra , Zambrano Ana Karina 
Published: March 2023

IntroductionCardiac laminopathies are caused by mutations in the LMNA gene and include a wide range of clinical manifestations involving electrical and mechanical changes in cardiomyocytes. In Ecuador, cardiovascular diseases were the primary cause of death in 2019, accounting for 26.5% of total deaths. Cardiac laminopathy-associated mutations involve genes coding for structural proteins with functions related to heart development and physiology.Family descriptionTwo Ecuadorian siblings, self-identified as mestizos, were diagnosed with cardiac laminopathies and suffered embolic strokes. Moreover, by performing Next-Generation Sequencing, a pathogenic variant (NM_170707.3:c.1526del) was found in the gene LMNA.Discussion and conclusionCurrently, genetic tests are an essential step for disease genetic counseling, including cardiovascular disease diagnosis. Identification of a genetic cause that may explain the risk of cardiac laminopathies in a family can help the post-test counseling and recommendations from the cardiologist. In the present report, a pathogenic variant ((NM_170707.3:c.1526del) has been identified in two Ecuadorian siblings with cardiac laminopathies. The LMNA gene codes for A-type laminar proteins that are associated with gene transcription regulation. Mutations in the LMNA gene cause laminopathies, disorders with diverse phenotypic manifestations. Moreover, understanding the molecular biology of the disease-causing mutations is essential in deciding the correct type of treatment.
Integrating global geochemical volcano rock composition with eruption history datasets
Authors: Oggier Frédérique , Widiwijayanti Christina , Costa Fidel 
Published: March 2023

The major element composition of volcanic rocks carries important information about the source and differentiation processes affecting the magma, the physical properties that allow it to erupt, and its eruptive style. Although global rock geochemical databases exist, these are not linked to volcanic eruption history which hampers our global understanding of the relationship between magma composition and eruption dynamics. Here, we integrate two global databases, the Geochemistry of Rocks of the Oceans and Continents (GEOROC) and the Holocene volcanoes of the world of the Global Volcanism Program (VOTW-GVP). The integration is based on matching the location name, geographic position and eruption time, which is automated by a tool called DashVolcano. The tool is open-source, accessible at https://github.com/feog/DashVolcano, and gives access to the integrated datasets via an interactive dashboard. DashVolcano is based on more than 138,000 volcanic rock samples and provides the basis for the identification of global relationships between eruption styles, volcano types, and rock composition for more than 700 volcanoes and their eruptions for the last 10,000 years. The combined record of the eruptive history and its corresponding geochemical rock composition that DashVolcano provides can be used for characterizing global geochemical differences between volcanoes, and should also prove useful for improved long-term hazard and risk evaluations.
Study on the correlation between river network patterns and topography in the Haihe River basin
Authors: Xingyuan Zhang , Fawen Li 
Published: March 2023

In recent decades, the river network patterns (RNPs) in China’s Haihe River basin have changed dramatically, and the topology of the river network has become increasingly complex. It is important to quantitatively study the correlation between river network patterns and topography (CRNPT) and the changes in the correlation. In this paper, the Haihe River basin was spatially gridded (4 km × 4 km), and different geomorphological areas were extracted for a multiarea study. We selected topographic and river network indicators and proposed new indicators to characterize regional topographic ‘stressfulness’ and then used redundancy analysis for correlation studies. The results showed that the variance of RNP explained by topography was 53.39%. The combined contribution of the topographic wetness index (TWI) and topographic wetness stress index (TSI) ranged from 35.66% to 78.29% in multiple areas, and the TSI showed stronger explanatory power. The regional effect of the CRNPT was significant, with mountains and transition areas having higher effects than plain areas. Compared to the natural river network, the CRNPT of the current river network was significantly lower. Among the RNP indicators, the artificial channel proportion (Pac) had the highest proportion of variance, and the CRNPT was strongly influenced by artificial channels. Artificial channels changed the consistency of topography with the RNP and reduced the topographic interpretation of the RNP, which may weaken the stability and hydrological connectivity of the river network. The variation in interpretation was related to the distribution of artificial channels, which showed a logarithmic function relationship between them.
Chronic airway disease as a major risk factor for fractures in osteopenic women: Nationwide cohort study
Authors: Kong Sung Hye , Jo Ae Jeong , Park Chan Mi , Park Kyun Ik , Yun Ji Eun , Kim Jung Hee 
Published: March 2023

IntroductionThe study aimed to demonstrate the risk factors for fractures and to develop prediction models for major osteoporotic and hip fractures in osteopenic patients using the nationwide cohort study in South Korea.MethodsThe study was a retrospective nationwide study using the national screening program for transitional ages from the National Health Insurance Services database in Korea from 2008 to 2019. Primary outcomes were incident fracture events of major osteoporotic and hip fractures. Major osteoporotic and hip fracture events were defined as diagnostic and procedural codes. Patients were followed until the fragility fractures, death, or 2019, whichever came first.ResultsAll participants were 66-year-old females, with a mean body mass index was 25.0 ± 3.1 kg/m2. During a median follow-up of 10.5 years, 26.9% and 6.7% of participants experienced major osteoporotic and hip fractures. In multivariate analysis, a history of fracture, chronic airway disease, falls, diabetes mellitus and cerebrovascular diseases were significant risk factors for major osteoporotic (hazard ratio [HR] 2.35 for a history of fracture; 1.17 for chronic airway disease; 1.10 for falls; 1.12 for diabetes mellitus; 1.11 for cerebrovascular disease) and hip fractures (HR 1.75 for a history of fracture; 1.54 for diabetes mellitus; 1.27 for cerebrovascular disease; 1.17 for fall; 1.15 for chronic airway disease). The performances of the prediction models were area under the receiver operating curve of 0.73 and 0.75 for major osteoporotic and hip fractures.ConclusionThe study presented prediction models of major osteoporotic and hip fractures for osteopenia patients using simple clinical features.
Incorporation size of lymph node metastasis focus and pre-ablation stimulated Tg could more effectively predict clinical outcomes in differentiated thyroid cancer patients without distant metastases
Authors: Xie Jiahao , Chen Pan , Wang Jing , Luo Xiaoqin , Luo Jiaxin , Xiong Xiaoli , Li Chunyan , Pan Liqin , Wu Juqing , Feng Huijuan , Ouyang Wei 
Published: March 2023

BackgroundThe size of lymph node metastasis (LNM) and pre-ablation stimulated Tg (ps-Tg) were key predictors of clinical prognosis in differentiated thyroid cancer (DTC) patients, however, very few studies combine the above two as predictors of clinical prognosis of DTC patients.MethodsPersistent/recurrent disease and clinicopathologic factors were analyzed in 543 DTC patients without distant metastases who underwent LN dissection, near-total/total thyroidectomy, and radioiodine ablation.ResultsIn the multivariate analysis, size of LNM, ps-Tg, and the activity of 131I significantly correlated with long-term remission. The optimal cutoff size of LNM 0.4 cm-1.4 cm (intermediate-risk patients) and &gt;1.4cm (high-risk patients) increased the recurrence risk (hazard ratio [95% CI], 4.674 [2.881-7.583] and 13.653 [8.135–22.913], respectively). Integration of ps-Tg into the reclassification risk stratification showed that ps-Tg ≤ 10.1 ng/mL was relevant to a greatly heightened possibility of long-term remission (92.2%–95.4% in low-risk patients, 67.3%–87.0% in intermediate-risk patients, and 32.3%–57.7% in high-risk patients).ConclusionThe cutoff of 0.4 cm and 1.4 cm for a definition of size of LNM in DTC patients without distant metastases can reclassify risk assessment, and incorporating ps-Tg could more effectively predict clinical outcomes and modify the postoperative management plan.
Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome
Authors: Lin Yunting , Chen Xiaohong , Xie Bobo , Guan Zhihong , Chen Xiaodan , Li Xiuzhen , Yi Peng , Du Rong , Mei Huifen , Liu Li , Zhang Wen , Zeng Chunhua 
Published: March 2023

Objective: Wiedemann-Steiner syndrome (WSS) is a rare autosomal dominant disorder caused by deleterious heterozygous variants of the KMT2A gene. This study aims to describe the phenotypic and genotypic features of Chinese WSS patients, and assess therapeutic effects of recombinant human growth hormone (rhGH).Methods: Eleven Chinese children with WSS were enrolled in our cohort. Their clinical, imaging, biochemical and molecular findings were analyzed retrospectively. Moreover, the phenotypic features of 41 previously reported Chinese WSS patients were reviewed and included in our analysis.Results: In our cohort, the 11 WSS patients presented with classic clinical manifestations, but with different frequencies. The most common clinical features were short stature (90.9%) and developmental delay (90.9%), followed by intellectual disability (72.7%). The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain. In the set comprising 52 Chinese WSS patients, the most common clinical and imaging manifestations were developmental delay (84.6%), intellectual disability (84.6%), short stature (80.8%) and delayed bone age (68.0%), respectively. Eleven different variants, including three known and eight novel variants, of the KMT2A gene were identified in our 11 WSS patients without a hotspot variant. Two patients were treated with rhGH and yielded satisfactory height gains, but one developed acceleration of bone age.Conclusion: Our study adds 11 new patients with WSS, reveals different clinical characteristics in Chinese WSS patients, and extends the mutational spectrum of the KMT2A gene. Our study also shares the therapeutic effects of rhGH in two WSS patients without GH deficiency.
An approach to the effects of longevity, sexual maturity, and reproduction on telomere length and oxidative stress in different Psittacidae species
Authors: Domínguez-de-Barros Angélica , Sifaoui Inés , Borecka Zuzanna , Dorta-Guerra Roberto , Lorenzo-Morales Jacob , Castro-Fuentes Rafael , Córdoba-Lanús Elizabeth 
Published: March 2023

Introduction: Aging is a multifactorial process that includes molecular changes such as telomere shortening. Telomeres shorten progressively with age in vertebrates, and their shortening rate has a significant role in determining the lifespan of a species. However, DNA loss can be enhanced by oxidative stress. The need for novel animal models has recently emerged as a tool to gather more information about the human aging process. Birds live longer than other mammals of the same size, and Psittacidae species are the most persevering of them, due to special key traits.Methods: We aimed to determine telomere length by qPCR, and oxidative stress status using colorimetric and fluorescence methods in different species of the order Psittaciformes with different lifespans.Results: We found that telomeres shorten with age for both long- and short-lived birds (p &lt; 0.001 and p = 0.004, respectively), with long-lived birds presenting longer telomeres than short-lived ones (p = 0.001). In addition, short-lived birds accumulated more oxidative stress products than long-lived birds (p = 0.013), who showed a better antioxidant capacity (p &lt; 0.001). Breeding was found related to telomere shortening in all species (p &lt; 0.001 and p = 0.003 for long- and short-lived birds). Short-lived birds, especially breeding females, increased their oxidative stress products when breeding (p = 0.021), whereas long-lived birds showed greater resistance and even increased their antioxidant capacity (p = 0.002).Conclusion: In conclusion, the relationship between age and telomere length in Psittacidae was verified. The influence of breeding increased cumulative oxidative damage in short-lived species, while long-lived species may counteract this damage.
Effects of the circulating environment of COVID-19 on platelet and neutrophil behavior
Authors: Fields Alexander T. , Andraska Elizabeth A. , Kaltenmeier Christof , Matthay Zachary A. , Herrera Kimberly , Nuñez-Garcia Brenda , Jones Chayse M. , Wick Katherine D. , Liu Silvia , Luo Jian-Hua , Yu Yan-Ping , Matthay Michael A. , Hendrickson Carolyn M. , Bainton Roland J. , Barrett Tessa J. , Berger Jeffrey S. , Neal Matthew D. , Kornblith Lucy Z. ,   the COVID-19 Associated Coagulopathy Inflammation and Thrombosis (Co-ACIT) Study Group
Published: March 2023

IntroductionThromboinflammatory complications are well described sequalae of Coronavirus Disease 2019 (COVID-19), and there is evidence of both hyperreactive platelet and inflammatory neutrophil biology that contributes to the thromoinflammatory milieu. It has been demonstrated in other thromboinflammatory diseases that the circulating environment may affect cellular behavior, but what role this environment exerts on platelets and neutrophils in COVID-19 remains unknown. We tested the hypotheses that 1) plasma from COVID-19 patients can induce a prothrombotic platelet functional phenotype, and 2) contents released from platelets (platelet releasate) from COVID-19 patients can induce a proinflammatory neutrophil phenotype. MethodsWe treated platelets with COVID-19 patient and disease control plasma, and measured their aggregation response to collagen and adhesion in a microfluidic parallel plate flow chamber coated with collagen and thromboplastin. We exposed healthy neutrophils to platelet releasate from COVID-19 patients and disease controls and measured neutrophil extracellular trap formation and performed RNA sequencing.ResultsWe found that COVID-19 patient plasma promoted auto-aggregation, thereby reducing response to further stimulation ex-vivo. Neither disease condition increased the number of platelets adhered to a collagen and thromboplastin coated parallel plate flow chamber, but both markedly reduced platelet size. COVID-19 patient platelet releasate increased myeloperoxidasedeoxyribonucleic acid complexes and induced changes to neutrophil gene expression.DiscussionTogether these results suggest aspects of the soluble environment circulating platelets, and that the contents released from those neutrophil behavior independent of direct cellular contact.
Excess of blood eosinophils prior to therapy correlates with worse prognosis in mesothelioma
Authors: Willems Mégane , Scherpereel Arnaud , Wasielewski Eric , Raskin Jo , Brossel Hélène , Fontaine Alexis , Grégoire Mélanie , Halkin Louise , Jamakhani Majeed , Heinen Vincent , Louis Renaud , Duysinx Bernard , Hamaidia Malik , Willems Luc 
Published: March 2023

BackgroundOnly a fraction of patients with malignant pleural mesothelioma (MPM) will respond to chemo- or immunotherapy. For the majority, the condition will irremediably relapse after 13 to 18 months. In this study, we hypothesized that patients’ outcome could be correlated to their immune cell profile. Focus was given to peripheral blood eosinophils that, paradoxically, can both promote or inhibit tumor growth depending on the cancer type.MethodsThe characteristics of 242 patients with histologically proven MPM were retrospectively collected in three centers. Characteristics included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR). The mean absolute eosinophil counts (AEC) were determined by averaging AEC data sets of the last month preceding the administration of chemo- or immunotherapy.ResultsAn optimal cutoff of 220 eosinophils/µL of blood segregated the cohort into two groups with significantly different median OS after chemotherapy (14 and 29 months above and below the threshold, p = 0.0001). The corresponding two-year OS rates were 28% and 55% in the AEC ≥ 220/µL and AEC &lt; 220/µL groups, respectively. Based on shorter median PFS (8 vs 17 months, p &lt; 0.0001) and reduced DCR (55.9% vs 35.2% at 6 months), the response to standard chemotherapy was significantly affected in the AEC ≥ 220/µL subset. Similar conclusions were also drawn from data sets of patients receiving immune checkpoint-based immunotherapy.ConclusionIn conclusion, baseline AEC ≥ 220/µL preceding therapy is associated with worse outcome and quicker relapse in MPM.