bluuebunny/crossref_metadata_2025 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

Introduction

Salmonella 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.

Methods

A galU gene mutant was successfully constructed by red homologous recombination technology, and biological characteristics were studied.

Results

The 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).

Discussion

The 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

Introduction

To 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.

Methods

To 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.

Results

Our 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.

Discussion

With 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

Introduction

Cardiac 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 description

Two 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 conclusion

Currently, 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

Introduction

The 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.

Methods

The 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.

Results

All 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.

Conclusion

The 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

Background

The 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.

Methods

Persistent/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.

Results

In 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 >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).

Conclusion

The 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.
Pattern recognition receptors in the development of nonalcoholic fatty liver disease and progression to hepatocellular carcinoma: An emerging therapeutic strategy
Authors: Huang Chen , Zhou Youlian , Cheng Jiemin , Guo Xue , Shou Diwen , Quan Ying , Chen Hanqing , Chen Huiting , Zhou Yongjian
Published: March 2023

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and has become the leading chronic liver disease worldwide. NAFLD is viewed as the hepatic manifestation of metabolic syndrome, ranging from simple steatosis and nonalcoholic steatohepatitis (NASH) to advanced fibrosis, eventually leading to cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of NAFLD progression is still not clear. Pattern recognition receptor (PRR)-mediated innate immune responses play a critical role in the initiation of NAFLD and the progression of NAFLD-related HCC. Toll-like receptors (TLRs) and the cyclic GMP-AMP (cGAMP) synthase (cGAS) are the two major PRRs in hepatocytes and resident innate immune cells in the liver. Increasing evidence indicates that the overactivation of TLRs and the cGAS signaling pathways may contribute to the development of liver disorders, including NAFLD progression. However, induction of PRRs is critical for the release of type I interferons (IFN-I) and the maturation of dendritic cells (DCs), which prime systemic antitumor immunity in HCC therapy. In this review, we will summarize the emerging evidence regarding the molecular mechanisms of TLRs and cGAS in the development of NAFLD and HCC. The dysfunction of PRR-mediated innate immune response is a critical determinant of NAFLD pathology; targeting and selectively inhibiting TLRs and cGAS signaling provides therapeutic potential for treating NALF-associated diseases in humans.
Validation of the burnup code MOTIVE with respect to fuel assembly decay heat data
Authors: Hannstein Volker , Behler Matthias , Henry Romain , Sommer Fabian
Published: March 2023

The burn-up code MOTIVE is a 3D code for fuel assembly inventory determination developed at GRS in recent years. It modularly couples an external Monte Carlo neutron transport code to the in-house inventory code VENTINA. In the present publication, we report on the validation of MOTIVE with respect to full-assembly decay heat measurements of light water reactor fuel. For this purpose, measurements on pressurized water reactor and boiling water reactor fuel assemblies from different facilities have been analyzed with MOTIVE. The calculated decay heat values are compared to the measured data in terms of absolute and relative deviations. These results are discussed and compared to other published validation analyses. Moreover, the observed deviations between measurements and calculations are analyzed further by taking into account the results of the validation of nuclide inventory determination with MOTIVE. The influence of possible biases of calculated nuclide densities important to decay heat at the given decay times are investigated and discussed.
Primary production in subsidized green-brown food webs
Authors: Zelnik Yuval R. , Manzoni Stefano , Bommarco Riccardo
Published: March 2023

Ecosystems worldwide receive large amounts of nutrients from both natural processes and human activities. While direct subsidy effects on primary production are relatively well-known (the green food web), the indirect effects of subsidies on producers as mediated by the brown food web and predators are poorly considered. With a dynamical green-brown food web model, parameterized using empirical estimates from the literature, we illustrate the effect of organic and inorganic nutrient subsidies on net primary production (NPP) (i.e., after removing loss to herbivory) in two idealized ecosystems—one terrestrial and one aquatic. We find that nutrient subsidies increase net primary production, an effect that saturates with increasing subsidies. Changing the quality of subsidies from inorganic to organic tends to increase net primary production in terrestrial ecosystems, but less often so in aquatic ecosystems. This occurs when organic nutrient inputs promote detritivores in the brown food web, and hence predators that in turn regulate herbivores, thereby promoting primary production. This previously largely overlooked effect is further enhanced by ecosystem properties such as fast decomposition and low rates of nutrient additions and demonstrates the importance of nutrient subsidy quality on ecosystem functioning.
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.
Case report: A novel heterozygous frameshift mutation of ACAN in a Chinese family with short stature and advanced bone age
Authors: Huang Hao , Jin Jieyuan , Xiang Rong , Wang Xia
Published: March 2023

Short stature (OMIM: 165800) is a common pediatric disorder. Any abnormality in the cartilage formation of the growth plate can cause short stature. Aggrecan, encoded by ACAN, is an important component of the extracellular matrix. Mutations in ACAN have been reported to cause short stature. In the present study, we enrolled a Chinese family with short stature and advanced bone age across three generations. Whole-exome sequencing (WES) was performed on the proband to detect the candidate genes causing short stature in family. A novel heterozygous frameshift mutation (NM_013227.3:c.7230delT; NP_001356197.1: p. Phe2410Leufs*9) of the ACAN gene was confirmed to be a genetic lesion in this family. This variant, which was located in a functional site globular 3 (G3) domain of ACAN and predicted to be deleterious by informatics programs, was co-segregated with the affected family members by performing Sanger sequencing. Literatures review of growth hormone (GH) treatment outcome of all previously reported ACAN patients suggesting that the G3 domain of ACAN may be critical in the development of short stature and growth hormone treatment. These findings not only contribute to the genetic diagnosis and counseling of the family, but will also expand the mutation spectrum of ACAN.
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 < 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 < 0.001). Breeding was found related to telomere shortening in all species (p < 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.
Evolutionary approach to construct robust codes for DNA-based data storage
Authors: Rasool Abdur , Jiang Qingshan , Wang Yang , Huang Xiaoluo , Qu Qiang , Dai Junbiao
Published: March 2023

DNA is a practical storage medium with high density, durability, and capacity to accommodate exponentially growing data volumes. A DNA sequence structure is a biocomputing problem that requires satisfying bioconstraints to design robust sequences. Existing evolutionary approaches to DNA sequences result in errors during the encoding process that reduces the lower bounds of DNA coding sets used for molecular hybridization. Additionally, the disordered DNA strand forms a secondary structure, which is susceptible to errors during decoding. This paper proposes a computational evolutionary approach based on a synergistic moth-flame optimizer by Levy flight and opposition-based learning mutation strategies to optimize these problems by constructing reverse-complement constraints. The MFOS aims to attain optimal global solutions with robust convergence and balanced search capabilities to improve DNA code lower bounds and coding rates for DNA storage. The ability of the MFOS to construct DNA coding sets is demonstrated through various experiments that use 19 state-of-the-art functions. Compared with the existing studies, the proposed approach with three different bioconstraints substantially improves the lower bounds of the DNA codes by 12–28% and significantly reduces errors.
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

Introduction

Thromboinflammatory 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.

Methods

We 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.

Results

We 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.

Discussion

Together these results suggest aspects of the soluble environment circulating platelets, and that the contents released from those neutrophil behavior independent of direct cellular contact.
VIGET: A web portal for study of vaccine-induced host responses based on Reactome pathways and ImmPort data
Authors: Brunson Timothy , Sanati Nasim , Huffman Anthony , Masci Anna Maria , Zheng Jie , Cooke Michael F. , Conley Patrick , He Yongqun , Wu Guanming
Published: March 2023

Host responses to vaccines are complex but important to investigate. To facilitate the study, we have developed a tool called Vaccine Induced Gene Expression Analysis Tool (VIGET), with the aim to provide an interactive online tool for users to efficiently and robustly analyze the host immune response gene expression data collected in the ImmPort/GEO databases. VIGET allows users to select vaccines, choose ImmPort studies, set up analysis models by choosing confounding variables and two groups of samples having different vaccination times, and then perform differential expression analysis to select genes for pathway enrichment analysis and functional interaction network construction using the Reactome’s web services. VIGET provides features for users to compare results from two analyses, facilitating comparative response analysis across different demographic groups. VIGET uses the Vaccine Ontology (VO) to classify various types of vaccines such as live or inactivated flu vaccines, yellow fever vaccines, etc. To showcase the utilities of VIGET, we conducted a longitudinal analysis of immune responses to yellow fever vaccines and found an intriguing complex activity response pattern of pathways in the immune system annotated in Reactome, demonstrating that VIGET is a valuable web portal that supports effective vaccine response studies using Reactome pathways and ImmPort data.
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

Background

Only 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.

Methods

The 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.

Results

An 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 < 220/µL groups, respectively. Based on shorter median PFS (8 vs 17 months, p < 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.

Conclusion

In conclusion, baseline AEC ≥ 220/µL preceding therapy is associated with worse outcome and quicker relapse in MPM.
Peutz-Jeghers syndrome with gastric-type mucinous endocervical adenocarcinoma and sex-cord tumor with annular tubules: A case report
Authors: Li Xuanyan , Qi Yue , Zhang Wenwen , Rao Yang , Zhang Na , Qu Pengpeng
Published: March 2023

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant genetic disorder characterized by mucocutaneous pigmentation and multiple hamartomatous polyps in the gastrointestinal tracts. About 11% of female PJS patients are diagnosed with Gastric-type endocervical adenocarcinoma (G-EAC) and about one third have a sex-cord tumor with annular tubules (SCTATs). Gastric-type endocervical adenocarcinoma is a special subtype of cervical adenocarcinoma which accounts for only 1–3%. Here we report a rare case of a 31-year-old woman affected with G-EAC and SCTAT accompanied by PJS. After surgery, we followed up for 5 years without recurrence.
Brevundimonas and Serratia as host systems for assessing associated environmental viromes and phage diversity by complementary approaches
Authors: Friedrich Ines , Neubauer Hannes , Kuritsyn Alisa , Bodenberger Bernhard , Tskhay Faina , Hartmann Sara , Poehlein Anja , Bömeke Mechthild , Hoppert Michael , Schneider Dominik , Hertel Robert , Daniel Rolf
Published: March 2023

Focusing on visible plaques for phage isolation leaves the question if we miss the diversity of non-plaque forming phages. We addressed this question through direct plaque-based isolation by employing the new hosts Brevundimonas pondensis LVF1 and Serratia marcescens LVF3 dsDNA, ssDNA, dsRNA, and ssRNA host-associated metavirome analysis. Of the 25 distinctive dsDNA phage isolates, 14 were associated with Brevundimonas and 11 with Serratia. TEM analysis revealed that 6 were myoviruses, 18 siphoviruses and 1 podovirus, while phages infecting Brevundimonas belonged all to siphoviruses. The associated viromes suggested a higher phage diversity in summer than in winter, and dsDNA phages were the dominant group. Isolation of vB_SmaP-Kaonashi was possible after investigating the viromes associated with Serratia, demonstrating the great potential of accompanying host-associated metavirome analysis. The ssDNA virome analysis showed that the B. pondensis LVF1 host is associated with Microviridae and Inoviridae phages, although none of them were isolated. The results demonstrated that the classical isolation technique is not exhausted, leading to the isolation of new dsDNA phages. It can be further improved by combination with metavirome techniques, which revealed further diversity.
Establishment, optimization, and application of genetic technology in Aspergillus spp.
Authors: Gao Jing , Liu Huiqing , Zhang Zhenzhen , Liang Zhihong
Published: March 2023

Aspergillus is widely distributed in nature and occupies a crucial ecological niche, which has complex and diverse metabolic pathways and can produce a variety of metabolites. With the deepening of genomics exploration, more Aspergillus genomic informations have been elucidated, which not only help us understand the basic mechanism of various life activities, but also further realize the ideal functional transformation. Available genetic engineering tools include homologous recombinant systems, specific nuclease based systems, and RNA techniques, combined with transformation methods, and screening based on selective labeling. Precise editing of target genes can not only prevent and control the production of mycotoxin pollutants, but also realize the construction of economical and efficient fungal cell factories. This paper reviewed the establishment and optimization process of genome technologies, hoping to provide the theoretical basis of experiments, and summarized the recent progress and application in genetic technology, analyzes the challenges and the possibility of future development with regard to Aspergillus.
The characteristics of soil microbial co-occurrence networks across a high-latitude forested wetland ecotone in China
Authors: Wu Di , Bai Hui , Zhao Caihong , Peng Mu , Chi Qi , Dai Yaping , Gao Fei , Zhang Qiang , Huang Minmin , Niu Ben
Published: March 2023

To understand the effect of seasonal variations on soil microbial communities in a forested wetland ecotone, here, we investigated the dynamics of the diversities and functions of both soil bacterial and fungal communities inhabiting three wetland types (forested wetland, shrub wetland and herbaceous vegetation wetland) from forest-wetland ecotone of northern Xiaoxing’an Mountains spanning different seasons. β-diversity of soil microbial communities varied significantly among different vegetation types (Betula platyphylla–Larix gmelinii, Alnus sibirica, Betula ovalifolia, and Carex schmidtii wetlands). We totally detected 34 fungal and 14 bacterial indicator taxa among distinctive groups by using Linear discriminant analysis effect size (LEfSe) analysis, and identified nine network hubs as the most important nodes detected in whole fungi, bacteria, and fungi–bacteria networks. At the vegetation type-level, bacterial and fungal microbiome living in C. schmidtii wetland soil possessed fewer positive interactions and lower modularity than those in other types of wetland soil. Furthermore, we also discovered that ectomycorrhizal fungi were dominant in the fungal microbiota existing in forested and shrub wetland soils, whereas arbuscular mycorrhizal fungi were predominated in those residing in herbaceous vegetation wetland soil. The distribution of the predicted bacterial functional enzymes also obviously varied among different vegetation-types. In addition, the correlation analysis further revealed that the key fungal network modules were significantly affected by the contents of total N and soil water-soluble K, whereas most of the bacterial network modules were remarkably positively driven by the contents of total N, soil water-soluble K, Mg and Na. Our study suggested that vegetation type are substantive factors controlling the diversity, composition and functional group of soil microbiomes from forest-wetland ecotone of northern Xiaoxing’an Mountains.
MiR-4521 perturbs FOXM1-mediated DNA damage response in breast cancer
Authors: Kuthethur Raviprasad , Adiga Divya , Kandettu Amoolya , Jerome Maria Sona , Mallya Sandeep , Mumbrekar Kamalesh Dattaram , Kabekkodu Shama Prasada , Chakrabarty Sanjiban
Published: March 2023

Introduction: Forkhead (FOX) transcription factors are involved in cell cycle control, cellular differentiation, maintenance of tissues, and aging. Mutation or aberrant expression of FOX proteins is associated with developmental disorders and cancers. FOXM1, an oncogenic transcription factor, is a promoter of cell proliferation and accelerated development of breast adenocarcinomas, squamous carcinoma of the head, neck, and cervix, and nasopharyngeal carcinoma. High FOXM1 expression is correlated with chemoresistance in patients treated with doxorubicin and Epirubicin by enhancing the DNA repair in breast cancer cells.

Method: miRNA-seq identified downregulation of miR-4521 in breast cancer cell lines. Stable miR-4521 overexpressing breast cancer cell lines (MCF-7, MDA-MB-468) were developed to identify miR-4521 target gene and function in breast cancer.

Results: Here, we showed that FOXM1 is a direct target of miR-4521 in breast cancer. Overexpression of miR-4521 significantly downregulated FOXM1 expression in breast cancer cells. FOXM1 regulates cell cycle progression and DNA damage response in breast cancer. We showed that miR-4521 expression leads to increased ROS levels and DNA damage in breast cancer cells. FOXM1 plays a critical role in ROS scavenging and promotes stemness which contributes to drug resistance in breast cancer. We observed that breast cancer cells stably expressing miR-4521 lead to cell cycle arrest, impaired FOXM1 mediated DNA damage response leading to increased cell death in breast cancer cells. Additionally, miR-4521-mediated FOXM1 downregulation perturbs cell proliferation, invasion, cell cycle progression, and epithelial-to-mesenchymal progression (EMT) in breast cancer.

Discussion: High FOXM1 expression has been associated with radio and chemoresistance contributing to poor patient survival in multiple cancers, including breast cancer. Our study showed that FOXM1 mediated DNA damage response could be targeted using miR-4521 mimics as a novel therapeutic for breast cancer.
Ferroptosis: Mechanism and potential applications in cervical cancer
Authors: Chang Xiangyu , Miao Jinwei
Published: March 2023

Ferroptosis is a distinct form of cell death mechanism different from the traditional ones. Ferroptosis is characterized biochemically by lipid peroxidation, iron accumulation, and glutathione deficiency. It has already demonstrated significant promise in antitumor therapy. Cervical cancer (CC) progression is closely linked to iron regulation and oxidative stress. Existing research has investigated the role of ferroptosis in CC. Ferroptosis could open up a new avenue of research for treating CC. This review will describe the factors and pathways and the research basis of ferroptosis, which is closely related to CC. Furthermore, the review may provide potential future directions for CC research, and we believe that more studies concerning the therapeutic implications of ferroptosis in CC will come to notice.
Early detection of cognitive decline in Alzheimer’s disease using eye tracking
Authors: Tokushige Shin-ichi , Matsumoto Hideyuki , Matsuda Shun-ichi , Inomata-Terada Satomi , Kotsuki Naoki , Hamada Masashi , Tsuji Shoji , Ugawa Yoshikazu , Terao Yasuo
Published: March 2023

Background

Patients with Alzheimer’s disease (AD) are known to exhibit visuospatial processing impairment, as reflected in eye movements from the early stages of the disease. We investigated whether the pattern of gaze exploration during visual tasks could be useful for detecting cognitive decline at the earliest stage.

Methods

Sixteen AD patients (age: 79.1 ± 7.9 years, Mini Mental State Examination [MMSE] score: 17.7 ± 5.3, mean ± standard deviation) and 16 control subjects (age: 79.4 ± 4.6, MMSE score: 26.9 ± 2.4) participated. In the visual memory task, subjects memorized presented line drawings for later recall. In the visual search tasks, they searched for a target Landolt ring of specific orientation (serial search task) or color (pop-out task) embedded among arrays of distractors. Using video-oculography, saccade parameters, patterns of gaze exploration, and pupil size change during task performance were recorded and compared between AD and control subjects.

Results

In the visual memory task, the number of informative regions of interest (ROIs) fixated was significantly reduced in AD patients compared to control subjects. In the visual search task, AD patients took a significantly longer time and more saccades to detect the target in the serial but not in pop-out search. In both tasks, there was no significant difference in the saccade frequency and amplitude between groups. On-task pupil modulation during the serial search task was decreased in AD. The number of ROIs fixated in the visual memory task and search time and saccade numbers in the serial search task differentiated both groups of subjects with high sensitivity, whereas saccade parameters of pupil size modulation were effective in confirming normal cognition from cognitive decline with high specificity.

Discussion

Reduced fixation on informative ROIs reflected impaired attentional allocation. Increased search time and saccade numbers in the visual search task indicated inefficient visual processing. Decreased on-task pupil size during visual search suggested decreased pupil modulation with cognitive load in AD patients, reflecting impaired function of the locus coeruleus. When patients perform the combination of these tasks to visualize multiple aspects of visuospatial processing, cognitive decline can be detected at an early stage with high sensitivity and specificity and its progression be evaluated.
Why help others? Insights from rodent to human early childhood research
Authors: Chen Ya-Qin , Han Shu , Yin Bin
Published: March 2023

Helping behavior are actions aiming at assisting another individual in need or to relieve their distress. The occurrence of this behavior not only depends on automated physiological mechanisms, such as imitation or emotional contagion, that is, the individual’s emotion and physiological state matching with others, but also needs motivation to sustain. From a comparative and developmental perspective, we discover that the motivation for helping behavior has a deep foundation both phylogenetically and ontogenetically. For example, empathic concern for others, relieving personal distress and the desire for social contact are universal motivations across rodents, non-human primates and human early childhoods. Therefore, a circle-layered model integrating evidences for motivation for helping behavior from rodent to human early childhood research is proposed: the inner circle contains the emotional-behavioral system and the outer circle contains the affective-cognitive system. The application of this model has significance for both behavioral neuroscience research and cultivating prosocial behavior in human society.
The conundrum of neuropsychiatric systemic lupus erythematosus: Current and novel approaches to diagnosis
Authors: Emerson Jonathan S. , Gruenewald Simon M. , Gomes Lavier , Lin Ming-Wei , Swaminathan Sanjay
Published: March 2023

Recognising neuropsychiatric involvement by systemic lupus erythematosus (SLE) is of growing importance, however many barriers to this exist at multiple levels of our currently available diagnostic algorithms that may ultimately delay its diagnosis and subsequent treatment. The heterogeneous and non-specific clinical syndromes, serological and cerebrospinal fluid (CSF) markers and neuroimaging findings that often do not mirror disease activity, highlight important research gaps in the diagnosis of neuropsychiatric SLE (NPSLE). Formal neuropsychological assessments or the more accessible screening metrics may also help improve objective recognition of cognitive or mood disorders. Novel serum and CSF markers, including autoantibodies, cytokines and chemokines have also shown increasing utility as part of diagnosis and monitoring, as well as in distinguishing NPSLE from SLE patients without SLE-related neuropsychiatric manifestations. Novel neuroimaging studies also expand upon our existing strategy by quantifying parameters that indicate microarchitectural integrity or provide an assessment of neuronal function. Some of these novel markers have shown associations with specific neuropsychiatric syndromes, suggesting that future research move away from considering NPSLE as a single entity but rather into its individually recognized neuropsychiatric manifestations. Nevertheless, it is likely that a composite panel of these investigations will be needed to better address the gaps impeding recognition of neuropsychiatric involvement by SLE.