bluuebunny/crossref_metadata_2025 huggingface dataset:
Progress and Current Status in Hajdu-Cheney Syndrome with Focus on Novel Genetic Research
Authors: Aida Natsuko , Ohno Tatsukuni , Azuma Toshifumi
Published: September 2022

Hajdu-Cheney syndrome (HCS) is a rare autosomal dominant manifestation of a congenital genetic disorder caused by a mutation in the NOTCH2 gene. NOTCH signaling has variations from NOTCH 1 to 4 and maintains homeostasis by determining and regulating the proliferation and differentiation of various cells. In HCS, the over-accumulated NOTCH2 causes abnormal bone resorption due to its continuous excessive signaling. HCS is characterized by progressive bone destruction, has complex wide-range clinical manifestations, and significantly impacts the patient’s quality of life. However, no effective treatment has been established for HCS to date. There are genetic variants of NOTCH2 that have been reported in the ClinVar database of the U.S. National Institutes of Health. In total, 26 mutant variants were detected based on the American College of Medical Genetics and Genomics (ACMC). To date, there has been no comprehensive compilation of HCS mutations. In this review, we provide the most comprehensive list possible of HCS variants, nucleotide changes, amino acid definitions, and molecular consequences reported to date, following the ACMC guidelines.
Dystocic Labor and Adrenergic and Noradrenergic Neurotransmitters: A Morphological Experimental Study
Authors: Malvasi Antonio , Vimercati Antonella , Ricci Ilaria , Picardi Nico , Cicinelli Ettore , Kosmas Ioannis , Baldini Giorgio Maria , Tinelli Andrea
Published: September 2022

Authors investigated the catecholaminergic neurotransmitters (chNs) quantitative modifications in pregnant uterine Lower Uterine Segment (LUS) during prolonged labor (PL) with the fetus in an occiput-posterior position (OPP), in occiput transverse position (OTP) and in fetal head asynclitism, all diagnosed by Intrapartum Ultrasonography (IU). The chNs neurotransmitters, particularly adrenaline (or epinephrine-A) and noradrenaline (or norepinephrine-N), were evaluated in LUS fragments sampled during CS of 34 patients undergoing urgent cesarean section (CS) in PL, compared to chNs fibers in the LUS of 36 women submitted to elective CS. All results were statistically analyzed to understand the differences in neurotransmitters morphological analysis by scanning electronic microscopy examination (SEM). The LUS fragments analysis revealed a reduction of A and N fibers in LUS during PL, compared with the expression of A and N fibers in LUS during elective CS. The PL for OPP, the OTP and asynclitism, all positions causing dystocia in labor lead to a reduction in neurotransmitters in LUS, with a uterine vascularization modification and a reduction in the contractility of smooth uterine cells. The A and N neurotransmitters reduction observed in PL negatively interferes with uterine contraction during labor.
The Italian Research on the Molecular Characterization of Maize Kernel Development
Authors: Consonni Gabriella , Castorina Giulia , Varotto Serena
Published: September 2022

The study of the genetic control of maize seed development and seed-related pathways has been one of the most important themes approached by the Italian scientific community. Maize has always attracted the interest of the Italian community of agricultural genetics since its beginning, as some of its founders based their research projects on and developed their “schools” by adopting maize as a reference species. Some of them spent periods in the United States, where maize was already becoming a model system, to receive their training. In this manuscript we illustrate the research work carried out in Italy by different groups that studied maize kernels and underline their contributions in elucidating fundamental aspects of caryopsis development through the characterization of maize mutants. Since the 1980s, most of the research projects aimed at the comprehension of the genetic control of seed development and the regulation of storage products’ biosyntheses and accumulation, and have been based on forward genetics approaches. We also document that for some decades, Italian groups, mainly based in Northern Italy, have contributed to improve the knowledge of maize genomics, and were both fundamental for further international studies focused on the correct differentiation and patterning of maize kernel compartments and strongly contributed to recent advances in maize research.
Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome
Authors: Yao Qiyang , Zou Xin , Liu Shihe , Wu Haowen , Shen Qiyang , Kang Jihong
Published: September 2022

Polycystic ovarian syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder. Circulating markers of oxidative stress are abnormal in women with PCOS. There is a close relationship between oxidative stress and insulin resistance (IR). However, little information is available about oxidative stress in the skeletal muscles of those affected by PCOS. In this study, PCOS was induced in prepubertal C57BL/6J mice by injection with dehydroepiandrosterone. Oxidative stress biomarkers were then measured in both serum and skeletal muscles. The underlying mechanisms were investigated in C2C12 myotubes treated with testosterone (T). We discovered increased oxidative biomarkers, increased ROS production, and damaged insulin sensitivity in the skeletal muscles of mice with PCOS. High levels of T caused mitochondrial dysfunction and increased ROS levels through the androgen receptor (AR)-nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) signaling pathway in C2C12 cells. Treatment of C2C12 cells with an antioxidant N-acetylcysteine (NAC) decreased T-induced ROS production, improved mitochondrial function, and reversed IR. Administration of NAC to mice with PCOS improved insulin sensitivity in the skeletal muscles of the animals. Hyperandrogenism caused mitochondrial dysfunction and redox imbalance in the skeletal muscles of mice with PCOS. We discovered that oxidative stress contributed to skeletal muscle IR in PCOS. Reducing ROS levels may improve the insulin sensitivity of skeletal muscles in patients with PCOS.
The Sequence Dependent Nanoscale Structure of CENP-A Nucleosomes
Authors: Stormberg Tommy , Lyubchenko Yuri L.
Published: September 2022

CENP-A is a histone variant found in high abundance at the centromere in humans. At the centromere, this histone variant replaces the histone H3 found throughout the bulk chromatin. Additionally, the centromere comprises tandem repeats of α-satellite DNA, which CENP-A nucleosomes assemble upon. However, the effect of the DNA sequence on the nucleosome assembly and centromere formation remains poorly understood. Here, we investigated the structure of nucleosomes assembled with the CENP-A variant using Atomic Force Microscopy. We assembled both CENP-A nucleosomes and H3 nucleosomes on a DNA substrate containing an α-satellite motif and characterized their positioning and wrapping efficiency. We also studied CENP-A nucleosomes on the 601-positioning motif and non-specific DNA to compare their relative positioning and stability. CENP-A nucleosomes assembled on α-satellite DNA did not show any positional preference along the substrate, which is similar to both H3 nucleosomes and CENP-A nucleosomes on non-specific DNA. The range of nucleosome wrapping efficiency was narrower on α-satellite DNA compared with non-specific DNA, suggesting a more stable complex. These findings indicate that DNA sequence and histone composition may be two of many factors required for accurate centromere assembly.
Improved Salinity Tolerance-Associated Variables Observed in EMS Mutagenized Wheat Lines
Authors: Lethin Johanna , Byrt Caitlin , Berger Bettina , Brien Chris , Jewell Nathaniel , Roy Stuart , Mousavi Hesam , Sukumaran Selvakumar , Olsson Olof , Aronsson Henrik
Published: September 2022

Salinity tolerance-associated phenotypes of 35 EMS mutagenized wheat lines originating from BARI Gom-25 were compared. Vegetative growth was measured using non-destructive image-based phenotyping. Five different NaCl concentrations (0 to 160 mM) were applied to plants 19 days after planting (DAP 19), and plants were imaged daily until DAP 38. Plant growth, water use, leaf Na+, K+ and Cl− content, and thousand kernel weight (TKW) were measured, and six lines were selected for further analysis. In saline conditions, leaf Na+, K+, and Cl− content variation on a dry weight basis within these six lines were ~9.3, 1.4, and 2.4-fold, respectively. Relative to BARI Gom-25, two (OA6, OA62) lines had greater K+ accumulation, three (OA6, OA10, OA62) had 50–75% lower Na+:K+ ratios, and OA62 had ~30% greater water-use index (WUI). OA23 had ~2.2-fold greater leaf Na+ and maintained TKW relative to BARI Gom-25. Two lines (OA25, OA52) had greater TKW than BARI Gom-25 when grown in 120 mM NaCl but similar Na+:K+, WUI, and biomass accumulation. OA6 had relatively high TKW, high leaf K+, and WUI, and low leaf Na+ and Cl−. Phenotypic variation revealed differing associations between the parameters measured in the lines. Future identification of the genetic basis of these differences, and crossing of lines with phenotypes of interest, is expected to enable the assessment of which combinations of parameters deliver the greatest improvement in salinity tolerance.
FBP1-Altered Carbohydrate Metabolism Reduces Leukemic Viability through Activating P53 and Modulating the Mitochondrial Quality Control System In Vitro
Authors: Xu Yi , Tran Lily , Tang Janet , Nguyen Vinh , Sewell Elisabeth , Xiao Jeffrey , Hino Christopher , Wasnik Samiksha , Francis-Boyle Olivia L. , Zhang Ke K. , Xie Linglin , Zhong Jiang F. , Baylink David J. , Chen Chien-Shing , Reeves Mark E. , Cao Huynh
Published: September 2022

Acute myeloid leukemia (AML)—the most frequent form of adult blood cancer—is characterized by heterogeneous mechanisms and disease progression. Developing an effective therapeutic strategy that targets metabolic homeostasis and energy production in immature leukemic cells (blasts) is essential for overcoming relapse and improving the prognosis of AML patients with different subtypes. With respect to metabolic regulation, fructose-1,6-bisphosphatase 1 (FBP1) is a gluconeogenic enzyme that is vital to carbohydrate metabolism, since gluconeogenesis is the central pathway for the production of important metabolites and energy necessary to maintain normal cellular activities. Beyond its catalytic activity, FBP1 inhibits aerobic glycolysis—known as the “Warburg effect”—in cancer cells. Importantly, while downregulation of FBP1 is associated with carcinogenesis in major human organs, restoration of FBP1 in cancer cells promotes apoptosis and prevents disease progression in solid tumors. Recently, our large-scale sequencing analyses revealed FBP1 as a novel inducible therapeutic target among 17,757 vitamin-D-responsive genes in MV4-11 or MOLM-14 blasts in vitro, both of which were derived from AML patients with FLT3 mutations. To investigate FBP1′s anti-leukemic function in this study, we generated a new AML cell line through lentiviral overexpression of an FBP1 transgene in vitro (named FBP1-MV4-11). Results showed that FBP1-MV4-11 blasts are more prone to apoptosis than MV4-11 blasts. Mechanistically, FBP1-MV4-11 blasts have significantly increased gene and protein expression of P53, as confirmed by the P53 promoter assay in vitro. However, enhanced cell death and reduced proliferation of FBP1-MV4-11 blasts could be reversed by supplementation with post-glycolytic metabolites in vitro. Additionally, FBP1-MV4-11 blasts were found to have impaired mitochondrial homeostasis through reduced cytochrome c oxidase subunit 2 (COX2 or MT-CO2) and upregulated PTEN-induced kinase (PINK1) expressions. In summary, this is the first in vitro evidence that FBP1-altered carbohydrate metabolism and FBP1-activated P53 can initiate leukemic death by activating mitochondrial reprogramming in AML blasts, supporting the clinical potential of FBP1-based therapies for AML-like cancers.
Impairment of Nucleolin Activity and Phosphorylation by a Trachylobane Diterpene from Psiadia punctulata in Cancer Cells
Authors: Bellone Maria Laura , Fiengo Lorenzo , Cerchia Carmen , Cotugno Roberta , Bader Ammar , Lavecchia Antonio , De Tommasi Nunziatina , Piaz Fabrizio Dal
Published: September 2022

Human nucleolin (hNcl) is a multifunctional protein involved in the progression of various cancers and plays a key role in other pathologies. Therefore, there is still unsatisfied demand for hNcl modulators. Recently, we demonstrated that the plant ent-kaurane diterpene oridonin inhibits hNcl but, unfortunately, this compound is quite toxic for healthy cells. Trachylobane diterpene 6,19-dihydroxy-ent-trachiloban-17-oic acid (compound 12) extracted from Psiadia punctulata (DC.) Vatke (Asteraceae) emerged as a ligand of hNcl from a cellular thermal shift assay (CETSA)-based screening of a small library of diterpenes. Effective interaction between this compound and the protein was demonstrated to occur both in vitro and inside two different types of cancer cells. Based on the experimental and computational data, a model of the hNcl/compound 12 complex was built. Because of this binding, hNcl mRNA chaperone activity was significantly reduced, and the level of phosphorylation of the protein was affected. At the biological level, cancer cell incubation with compound 12 produced a cell cycle block in the subG0/G1 phase and induced early apoptosis, whereas no cytotoxicity towards healthy cells was observed. Overall, these results suggested that 6,19-dihydroxy-ent-trachiloban-17-oic could represent a selective antitumoral agent and a promising lead for designing innovative hNcl inhibitors also usable for therapeutic purposes.
Mitochondrial DNA Repair in Neurodegenerative Diseases and Ageing
Authors: Bazzani Veronica , Equisoain Redin Mara , McHale Joshua , Perrone Lorena , Vascotto Carlo
Published: September 2022

Mitochondria are the only organelles, along with the nucleus, that have their own DNA. Mitochondrial DNA (mtDNA) is a double-stranded circular molecule of ~16.5 kbp that can exist in multiple copies within the organelle. Both strands are translated and encode for 22 tRNAs, 2 rRNAs, and 13 proteins. mtDNA molecules are anchored to the inner mitochondrial membrane and, in association with proteins, form a structure called nucleoid, which exerts a structural and protective function. Indeed, mitochondria have evolved mechanisms necessary to protect their DNA from chemical and physical lesions such as DNA repair pathways similar to those present in the nucleus. However, there are mitochondria-specific mechanisms such as rapid mtDNA turnover, fission, fusion, and mitophagy. Nevertheless, mtDNA mutations may be abundant in somatic tissue due mainly to the proximity of the mtDNA to the oxidative phosphorylation (OXPHOS) system and, consequently, to the reactive oxygen species (ROS) formed during ATP production. In this review, we summarise the most common types of mtDNA lesions and mitochondria repair mechanisms. The second part of the review focuses on the physiological role of mtDNA damage in ageing and the effect of mtDNA mutations in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Considering the central role of mitochondria in maintaining cellular homeostasis, the analysis of mitochondrial function is a central point for developing personalised medicine.
Targeting EZH2 Promotes Chemosensitivity of BCL-2 Inhibitor through Suppressing PI3K and c-KIT Signaling in Acute Myeloid Leukemia
Authors: Yang Chan , Gu Yan , Ge Zheng , Song Chunhua
Published: September 2022

Acute myeloid leukemia (AML) is one of the most common hematological malignancies with high heterogeneity, characterized by a differentiating block at the early progenitor stage. The selective BCL-2 inhibitor, Venetoclax (Ven), has shown exciting clinical results in a certain group of AML patients. However, Ven alone is insufficient to reach an enduringly complete response, which leads to the concern of Ven resistance. Alternative combined therapies with Ven are demanded in AML. Here, we reported the synergistic effect and molecular mechanism of the enhancer of zeste homolog 2 (EZH2) inhibitor DZNeP with Ven in AML cells. Results showed that the combination of DZNeP with Ven significantly induces cell proliferation arrest compared to single-drug control in AML cells and primary samples, and CalcuSyn analysis showed their significant synergy. The combination also significantly promotes apoptosis and increases the expression of pro-apoptotic proteins. The whole transcriptome analysis showed that phosphoinositide-3-kinase-interacting protein1 (PIK3IP1), the PI3K/AKT/mTOR signaling suppressor, is upregulated upon DZNeP treatment. Moreover, EZH2 is upregulated but PIK3IP1 is downregulated in 88 newly diagnosed AML cohorts compared to 70 healthy controls, and a higher expression of EZH2 is associated with poor outcomes in AML patients. Particularly, the combination of DZNeP with Ven dramatically eliminated CD117 (c-KIT) (+) AML blasts, suggesting the effect of the combination on tumor stem cells. In summary, our data indicated that DZNeP increases the sensitivity of Ven in AML by affecting PI3K and c-KIT signaling in AML. Our results also suggested that the therapeutic targeting of both EZH2 and BCL-2 provides a novel potential combined strategy against AML.
Tuning Functionalized Ionic Liquids for CO2 Capture
Authors: Zhang Ruina , Ke Quanli , Zhang Zekai , Zhou Bing , Cui Guokai , Lu Hanfeng
Published: September 2022

The increasing concentration of CO2 in the atmosphere is related to global climate change. Carbon capture, utilization, and storage (CCUS) is an important technology to reduce CO2 emissions and to deal with global climate change. The development of new materials and technologies for efficient CO2 capture has received increasing attention among global researchers. Ionic liquids (ILs), especially functionalized ILs, with such unique properties as almost no vapor pressure, thermal- and chemical-stability, non-flammability, and tunable properties, have been used in CCUS with great interest. This paper focuses on the development of functionalized ILs for CO2 capture in the past decade (2012~2022). Functionalized ILs, or task-specific ILs, are ILs with active sites on cations or/and anions. The main contents include three parts: cation-functionalized ILs, anion-functionalized ILs, and cation-anion dual-functionalized ILs for CO2 capture. In addition, classification, structures, and synthesis of functionalized ILs are also summarized. Finally, future directions, concerns, and prospects for functionalized ILs in CCUS are discussed. This review is beneficial for researchers to obtain an overall understanding of CO2-philic ILs. This work will open a door to develop novel IL-based solvents and materials for the capture and separation of other gases, such as SO2, H2S, NOx, NH3, and so on.
Autophagy in the Lifetime of Plants: From Seed to Seed
Authors: Wang Song , Hu Weiming , Liu Fen
Published: September 2022

Autophagy is a highly conserved self-degradation mechanism in eukaryotes. Excess or harmful intracellular content can be encapsulated by double-membrane autophagic vacuoles and transferred to vacuoles for degradation in plants. Current research shows three types of autophagy in plants, with macroautophagy being the most important autophagic degradation pathway. Until now, more than 40 autophagy-related (ATG) proteins have been identified in plants that are involved in macroautophagy, and these proteins play an important role in plant growth regulation and stress responses. In this review, we mainly introduce the research progress of autophagy in plant vegetative growth (roots and leaves), reproductive growth (pollen), and resistance to biotic (viruses, bacteria, and fungi) and abiotic stresses (nutrients, drought, salt, cold, and heat stress), and we discuss the application direction of plant autophagy in the future.
Female Germ Cell Development in Chickens and Humans: The Chicken Oocyte Enriched Genes Convergent and Divergent with the Human Oocyte
Authors: Rengaraj Deivendran , Han Jae Yong
Published: September 2022

The development of germ cells and other physiological events in the differentiated ovary of humans are highly conserved with several mammalian species, except for the differences in timing. However, comparative knowledge on this topic is very scarce with respect to humans and lower vertebrates, such as chickens. In chickens, female germ cells enter into meiosis around embryonic day (E) 15.5 and are arrested in meiotic prophase I as primary oocytes. The oocytes arrested in meiosis I are accumulated in germ-cell cysts; shortly after hatching, they are enclosed by flattened granulosa cells in order to form primordial follicles. In humans, the process of meiotic recombination in female germ cells begins in the 10–11th week of gestation, and primordial follicles are formed at around week 20. In this review, we comprehensively elucidate both the conservation and the species-specific differences between chickens and humans with respect to germ cell, oocyte, and follicle development. Importantly, we provide functional insights into a set of chicken oocyte enriched genes (from E16 to 1 week post-hatch) that show convergent and divergent expression patterns with respect to the human oocyte (from week 11 to 26).
Molecular Research of Lipid Peroxidation and Antioxidant Enzyme Activity of Comamonas testosteroni Bacterial Cells under the Hexachlorobenzene Impact
Authors: Dimova Mariia , Tugai Andrii , Tugai Tetiana , Iutynska Galyna , Dordevic Dani , Kushkevych Ivan
Published: September 2022

The species of Comamonas testosteroni is the most common human pathogen of the genus, which can be associated with acute appendicitis, infections of the bloodstream, the peritoneal cavity, cerebrospinal fluid, inflammatory bowel disease, and in general, bacteremia. According to the literature, Comamonas testosteroni has destructive activity to a wide range of toxic chemical compounds, including chlorobenzenes. The specified strains were isolated from the soil of the organochlorine waste landfill, where hexachlorobenzene (HCB) was predominant. These strains were expected to be capable of degrading HCB. Microbiological (bacterial enrichment and cultivating, bacterial biomass obtaining), molecular biology, biochemical (enzymatic activities, malondialdehyde measuring, peroxidation lipid products measuring), and statistical methods were carried out in this research. The reaction of both strains (UCM B-400 and UCM B-401) to the hexachlorobenzene presence differed in the content of diene and triene conjugates and malondialdehyde, as well as different catalase and peroxidase activity levels. In terms of primary peroxidation products, diene conjugates were lower, except conditions with 20 mg/L HCB, where these were higher up to two times, than the pure control. Malondialdehyde in strain B-400 cells decreased up to five times, in B-401, but increased up to two times, compared to the pure control. Schiff bases in strain B-400 cells were 2–3 times lower than the pure control. However, in B-401 cells Schiff bases under higher HCB dose were in the same level with the pure control. Catalase activity was 1.5 times higher in all experimental variants, compared to the pure control (in the strain B-401 cells), but in the B-400 strain, cells were 2 times lower, compared to the pure control. The response of the two strains to hexachlorobenzene was similar only in peroxidase activity terms, which was slightly higher compared to the pure control. The physiological response of Comamonas testosteroni strains to hexachlorobenzene has a typical strain reaction. The physiological response level of these strains to hexachlorobenzene confirms its tolerance, and indirectly, the ability to destroy the specified toxic compound.
Migraine Pharmacological Treatment and Cognitive Impairment: Risks and Benefits
Authors: Russo Mirella , De Rosa Matteo A. , Calisi Dario , Consoli Stefano , Evangelista Giacomo , Dono Fedele , Santilli Matteo , Granzotto Alberto , Onofrj Marco , Sensi Stefano L.
Published: September 2022

Migraine is a common neurological disorder impairing the quality of life of patients. The condition requires, as an acute or prophylactic line of intervention, the frequent use of drugs acting on the central nervous system (CNS). The long-term impact of these medications on cognition and neurodegeneration has never been consistently assessed. The paper reviews pharmacological migraine treatments and discusses their biological and clinical effects on the CNS. The different anti-migraine drugs show distinct profiles concerning neurodegeneration and the risk of cognitive deficits. These features should be carefully evaluated when prescribing a pharmacological treatment as many migraineurs are of scholar or working age and their performances may be affected by drug misuse. Thus, a reconsideration of therapy guidelines is warranted. Furthermore, since conflicting results have emerged in the relationship between migraine and dementia, future studies must consider present and past pharmacological regimens as potential confounding factors.
Mucopolysaccharidosis-Plus Syndrome: Report on a Polish Patient with a Novel VPS33A Variant with Comparison with Other Described Patients
Authors: Lipiński Patryk , Szczałuba Krzysztof , Buda Piotr , Zakharova Ekaterina Y. , Baydakova Galina , Ługowska Agnieszka , Różdzyńska-Świątkowska Agnieszka , Cyske Zuzanna , Węgrzyn Grzegorz , Pollak Agnieszka , Płoski Rafał , Tylki-Szymańska Anna
Published: September 2022

Eleven patients from Yakutia with a new lysosomal disease assumed then as mucopolysaccharidosis-plus syndrome (MPS-PS) were reported by Gurinova et al. in 2014. Up to now, a total number of 39 patients have been reported; in all of them, the c.1492C>T (p.Arg498Trp) variant of the VPS33A gene was detected. Here, we describe the first Polish MPS-PS patient with a novel homozygous c.599G>C (p.Arg200Pro) VPS33A variant presenting over 12 years of follow-up with some novel clinical features, including fetal ascites (resolved spontaneously), recurrent joint effusion and peripheral edemas, normal growth, and visceral obesity. Functional analyses revealed a slight presence of chondroitin sulphate (only) in urine glycosaminoglycan electrophoresis, presence of sialooligosaccharides in urine by thin-layer chromatography, and normal results of lysosomal enzymes activity and lysosphingolipids concentration in dried blood spot. The comparison with other MPS-PS described cases was also provided. The presented description of the natural history of MPS-PS in our patient may broaden the spectrum of phenotypes in this disease.
Triclosan and Its Consequences on the Reproductive, Cardiovascular and Thyroid Levels
Authors: Marques Ana C. , Mariana Melissa , Cairrao Elisa
Published: September 2022

Hygiene is essential to avoid diseases, and this is thanks to daily cleaning and disinfection habits. Currently, there are numerous commercial products containing antimicrobial agents, and although they are efficient in disinfecting, it is still not known the effect of the constant use of these products on human health. In fact, a massive use of disinfectants has been observed due to COVID-19, but the possible adverse effects are not yet known. Triclosan is one of the antimicrobial agents used in cosmetic products, toothpaste, and disinfectants. This compound is an endocrine disruptor, which means it can interfere with hormonal function, with its estrogenic and androgenic activity having already been stated. Even if the use of triclosan is well-regulated, with the maximum allowed concentration in the European Union of 0.3% (m/m), its effects on human health are still uncertain. Studies in animals and humans suggest the possibility of harmful health outcomes, particularly for the reproductive system, and in a less extent for the cardiovascular and thyroid functions. Thus, the purpose of this review was to analyse the possible implications of the massive use of triclosan, mainly on the reproductive and cardiovascular systems and on the thyroid function, both in animals and humans.
On the Relevance of Soft Tissue Sarcomas Metabolic Landscape Mapping
Authors: Esperança-Martins Miguel , F.Duarte Iola , Rodrigues Mara , Soares do Brito Joaquim , López-Presa Dolores , Costa Luís , Fernandes Isabel , Dias Sérgio
Published: September 2022

Soft tissue sarcomas (STS) prognosis is disappointing, with current treatment strategies being based on a “fit for all” principle and not taking distinct sarcoma subtypes specificities and genetic/metabolic differences into consideration. The paucity of precision therapies in STS reflects the shortage of studies that seek to decipher the sarcomagenesis mechanisms. There is an urge to improve STS diagnosis precision, refine STS classification criteria, and increase the capability of identifying STS prognostic biomarkers. Single-omics and multi-omics studies may play a key role on decodifying sarcomagenesis. Metabolomics provides a singular insight, either as a single-omics approach or as part of a multi-omics strategy, into the metabolic adaptations that support sarcomagenesis. Although STS metabolome is scarcely characterized, untargeted and targeted metabolomics approaches employing different data acquisition methods such as mass spectrometry (MS), MS imaging, and nuclear magnetic resonance (NMR) spectroscopy provided important information, warranting further studies. New chromatographic, MS, NMR-based, and flow cytometry-based methods will offer opportunities to therapeutically target metabolic pathways and to monitorize the response to such metabolic targeting therapies. Here we provide a comprehensive review of STS omics applications, comprising a detailed analysis of studies focused on the metabolic landscape of these tumors.
Spin-Crossover and Slow Magnetic Relaxation Behavior in Hexachlororhenate(IV) Salts of Mn(III) Complexes [Mn(5-Hal-sal2323)]2[ReCl6] (Hal = Cl, Br)
Authors: Tiunova Aleksandra V. , Kazakova Anna V. , Korchagin Denis V. , Shilov Gennady V. , Aldoshin Sergey M. , Dmitriev Aleksei I. , Zhidkov Mikhail V. , Zakharov Konstantin V. , Yagubskii Eduard B.
Published: September 2022

The cationic complexes of Mn(III) with the 5-Hal-sal2323 (Hal = Cl, Br) ligands and a paramagnetic doubly charged counterion [ReCl6]2− have been synthesized: [Mn(5-Cl-sal2323)]2[ReCl6] (1) and [Mn(5-Br-sal2323)]2[ReCl6] (2). Their crystal structures and magnetic properties have been studied. These isostructural two-component ionic compounds show a thermally induced spin transition at high temperature associated with the cationic subsystem and a field-induced slow magnetic relaxation of magnetization at cryogenic temperature, associated with the anionic subsystem. The compounds are the first examples of the coexistence of spin crossover and field-induced slow magnetic relaxation in the family of known [MnIII(sal2323)] cationic complexes with various counterions.
Hsp90 as a Myokine: Its Association with Systemic Inflammation after Exercise Interventions in Patients with Myositis and Healthy Subjects
Authors: Švec Xiao , Štorkánová Hana , Špiritović Maja , Slabý Kryštof , Oreská Sabína , Pekáčová Aneta , Heřmánková Barbora , Bubová Kristýna , Česák Petr , Khouri Haya , Amjad Gulalai , Mann Heřman , Komarc Martin , Pavelka Karel , Šenolt Ladislav , Zámečník Josef , Vencovský Jiří , Tomčík Michal
Published: September 2022

Compelling evidence supports the health benefits of physical exercise on the immune system, possibly through the molecules secreted by the skeletal muscles known as myokines. Herein, we assessed the impact of exercise interventions on plasma Heat shock protein 90 (Hsp90) levels in 27 patients with idiopathic inflammatory myopathies (IIM) compared with 23 IIM patients treated with standard-of-care immunosuppressive therapy only, and in 18 healthy subjects undergoing strenuous eccentric exercise, and their associations with the traditional serum markers of muscle damage and inflammation. In contrast to IIM patients treated with pharmacotherapy only, in whom we demonstrated a significant decrease in Hsp90 over 24 weeks, the 24-week exercise program resulted in a stabilization of Hsp90 levels. These changes in Hsp90 levels were associated with changes in several inflammatory cytokines/chemokines involved in the pathogenesis of IIM or muscle regeneration in general. Strenuous eccentric exercise in healthy volunteers induced a brief increase in Hsp90 levels with a subsequent return to baseline levels at 14 days after the exercise, with less pronounced correlations to systemic inflammation. In this study, we identified Hsp90 as a potential myokine and mediator for exercise-induced immune response and as a potential biomarker predicting improvement after physiotherapy in muscle endurance in IIM.
Special Issue on Information Retrieval, Recommender Systems and Adaptive Systems
Authors: Polignano Marco , Semeraro Giovanni
Published: September 2022

The current spread of the Internet across an ever-increasing number of devices, including mobile and IoT devices, has created an enormous flow of data [...]
Exploring Immersive Learning Experiences: A Survey
Authors: Kuhail Mohammad Amin , ElSayary Areej , Farooq Shahbano , Alghamdi Ahlam
Published: September 2022

Immersive technologies have been shown to significantly improve learning as they can simplify and simulate complicated concepts in various fields. However, there is a lack of studies that analyze the recent evidence-based immersive learning experiences applied in a classroom setting or offered to the public. This study presents a systematic review of 42 papers to understand, compare, and reflect on recent attempts to integrate immersive technologies in education using seven dimensions: application field, the technology used, educational role, interaction techniques, evaluation methods, and challenges. The results show that most studies covered STEM (science, technology, engineering, math) topics and mostly used head-mounted display (HMD) virtual reality in addition to marker-based augmented reality, while mixed reality was only represented in two studies. Further, the studies mostly used a form of active learning, and highlighted touch and hardware-based interactions enabling viewpoint and select tasks. Moreover, the studies utilized experiments, questionnaires, and evaluation studies for evaluating the immersive experiences. The evaluations show improved performance and engagement, but also point to various usability issues. Finally, we discuss implications and future research directions, and compare our findings with related review studies.
Classification of Malaria Using Object Detection Models
Authors: Krishnadas Padmini , Chadaga Krishnaraj , Sampathila Niranjana , Rao Santhosha , S. Swathi K. , Prabhu Srikanth
Published: September 2022

Malaria poses a global health problem every day, as it affects millions of lives all over the world. A traditional diagnosis requires the manual inspection of blood smears from the patient under a microscope to check for the malaria parasite. This is often time consuming and subject to error. Thus, the automated detection and classification of the malaria type and stage of progression can provide a quicker and more accurate diagnosis for patients. In this research, we used two object detection models, YOLOv5 and scaled YOLOv4, to classify the stage of progression and type of malaria parasite. We also used two different datasets for the classification of stage and parasite type while assessing the viability of the dataset for the task. The dataset used is comprised of microscopic images of red blood cells that were either parasitized or uninfected. The infected cells were classified based on two broad categories: the type of malarial parasite causing the infection and the stage of progression of the disease. The dataset was manually annotated using the LabelImg tool. The images were then augmented to enhance model training. Both models YOLOv5 and scaled YOLOv4 proved effective in classifying the type of parasite. Scaled YOLOv4 was in the lead with an accuracy of 83% followed by YOLOv5 with an accuracy of 78.5%. The proposed models may be useful for the medical professionals in the accurate diagnosis of malaria and its stage prediction.
Cytochrome P450 Genes Expressed in Phasmatodea Midguts
Authors: Shelomi Matan
Published: September 2022

Cytochrome P450s (CYPs) are xenobiotic detoxification genes found in most eukaryotes, and linked in insects to the tolerance of plant secondary chemicals and insecticide resistance. The number and diversity of CYP clans, families, and subfamilies that an organism produces could correlate with its dietary breadth or specialization. This study examined the CYP diversity expressed in the midguts of six species of folivorous stick insects (Phasmatodea), to identify their CYP complement and see if any CYPs correlate with diet toxicity or specialization, and see what factors influenced their evolution in this insect order. CYP genes were mined from six published Phasmatodea transcriptomes and analyzed phylogenetically. The Phasmatodea CYP complement resembles that of other insects, though with relatively low numbers, and with significant expansions in the CYP clades 6J1, 6A13/14, 4C1, and 15A1. The CYP6 group is known to be the dominant CYP family in insects, but most insects have no more than one CYP15 gene, so the function of the multiple CYP15A1 genes in Phasmatodea is unknown, with neofunctionalization following gene duplication hypothesized. No correlation was found between CYPs and diet specialization or toxicity, with some CYP clades expanding within the Phasmatodea and others likely inherited from a common ancestor.
Sublethal and Transgenerational Toxicities of Chlorfenapyr on Biological Traits and Enzyme Activities of Paracoccus marginatus (Hemiptera: Pseudococcidae)
Authors: Li Jian-Yu , Chen Yan-Ting , Wang Qiu-Yue , Zheng Li-Zhen , Fu Jian-Wei , Shi Meng-Zhu
Published: September 2022

Papaya mealybug, Paracoccus marginatus Williams and Granara de Willink (Hemiptera: Pseudococcidae), is an economically important, invasive insect that is now distributed worldwide. Chlorfenapyr has been demonstrated to have a significant control effect on P. marginatus. In order to evaluate the sublethal and transgenerational effects of chlorfenapyr on P. marginatus, the life table data of three consecutive generations were collected and analyzed by the age stage, two-sex life table method, and the enzyme activities were assayed using a spectrophotometer. The results showed that exposure to the insecticide had significant effects on the biological traits of subsequent generations of P. marginatus, and a higher intrinsic rate of increase (r), finite rate of increase (λ), net reproductive rate (R0), and a shorter mean generation time (T) were observed in the chlorfenapyr-treated F1 mealybugs. Enzyme activity assays showed that chlorfenapyr significantly inhibited the activities of catalase (CAT) and peroxidase (POD) while activating the activities of superoxide dismutase (SOD), which suggested that SOD, CAT, and POD may play an important role in the self-defense of P. marginatus against chlorfenapyr. These results conclusively demonstrated that exposure of P. marginatus to sublethal concentrations of chlorfenapyr induced hormetic effects on the F1 generation while having negative effects on the F0 and F3 generations.
Discrepancy in Sterol Usage between Two Polyphagous Caterpillars, Mythimna separata and Spodoptera frugiperda
Authors: Tang Rui , Liang Junhao , Jing Xiangfeng , Liu Tongxian
Published: September 2022

Insects are sterol auxotrophs and typically obtain sterols from food. However, the sterol demand and metabolic capacity vary greatly among species, even for closely related species. The low survival of many insects on atypical sterols, such as cholestanol and cholestanone, raises the possibility of using sterol-modified plants to control insect herbivore pests. In this study, we evaluated two devastating migratory crop pests, Mythimna separata and Spodoptera frugiperda, in response to atypical sterols and explored the reasons that caused the divergences in sterol nutritional biology between them. Contrary to M. separata, S. frugiperda had unexpectedly high survival on cholestanone, and nearly 80% of the individuals pupated. Comparative studies, including insect response to multiple diets and larval body sterol/steroids analysis, were performed to explain their differences in cholestanone usage. Our results showed that, in comparison to M. separata, the superiority of S. frugiperda on cholestanone can be attributed to its higher efficiency of converting ketone into available stanol and its lower demand for sterols, which resulted in a better survival when cholesterol was unavailable. This research will help us to better understand insect sterol nutritional biology and the potential of using atypical sterols to control herbivorous insect pests.
The Impact of Crystal Light Yield Non-Proportionality on a Typical Calorimetric Space Experiment: Beam Test Measurements and Monte Carlo Simulations
Authors: Pacini Lorenzo , Adriani Oscar , Berti Eugenio , Betti Pietro , Bigongiari Gabriele , Bonechi Lorenzo , Bongi Massimo , Bottai Sergio , Brogi Paolo , Castellini Guido , Checchia Caterina , D’Alessandro Raffaello , Detti Sebastiano , Finetti Noemi , Maestro Paolo , Marrocchesi Pier Simone , Mori Nicola , Olmi Miriam , Papini Paolo , Poggiali Claudia , Ricciarini Sergio , Spillantini Piero , Starodubtsev Oleksandr , Stolzi Francesco , Tiberio Alessio , Vannuccini Elena
Published: September 2022

Calorimetric space experiments were employed for the direct measurements of cosmic-ray spectra above the TeV region. According to several theoretical models and recent measurements, relevant features in both electron and nucleus fluxes are expected. Unfortunately, sizable disagreements among the current results of different space calorimeters exist. In order to improve the accuracy of future experiments, it is fundamental to understand the reasons of these discrepancies, especially since they are not compatible with the quoted experimental errors. A few articles of different collaborations suggest that a systematic error of a few percentage points related to the energy-scale calibration could explain these differences. In this work, we analyze the impact of the nonproportionality of the light yield of scintillating crystals on the energy scale of typical calorimeters. Space calorimeters are usually calibrated by employing minimal ionizing particles (MIPs), e.g., nonshowering proton or helium nuclei, which feature different ionization density distributions with respect to particles included in showers. By using the experimental data obtained by the CaloCube collaboration and a minimalist model of the light yield as a function of the ionization density, several scintillating crystals (BGO, CsI(Tl), LYSO, YAP, YAG and BaF2) are characterized. Then, the response of a few crystals is implemented inside the Monte Carlo simulation of a space calorimeter to check the energy deposited by electromagnetic and hadronic showers. The results of this work show that the energy scale obtained by MIP calibration could be affected by sizable systematic errors if the nonproportionality of scintillation light is not properly taken into account.
The Impact of Nonconvulsive Status Epilepticus after Cardiac Surgery on Outcome
Authors: Skhirtladze-Dworschak Keso , Felli Alessia , Aull-Watschinger Susanne , Jung Rebekka , Mouhieddine Mohamed , Zuckermann Andreas , Tschernko Edda , Dworschak Martin , Pataraia Ekaterina
Published: September 2022

Neurological complications after heart surgery are associated with tremendous morbidity and mortality. Nonconvulsive status epilepticus (NCSE), which can only be verified by EEG, may cause secondary brain damage. Its frequency and its impact on outcomes after cardiac surgery is still unclear. We collected the neurological files and clinical data of all our patients after heart surgery who, in the course of their ICU stay, had been seen by a neurologist who ordered an EEG. Within 18 months, 1457 patients had cardiac surgery on cardiopulmonary bypass. EEG was requested for 89 patients. Seizures were detected in 39 patients and NCSE was detected in 11 patients. Open heart surgery was performed in all 11 NSCE patients, of whom eight showed concomitant brain insults. None had a history of epilepsy. Despite the inhibition of seizure activity with antiseizure medication, clinical improvement was only noted in seven NCSE patients, three of whom were in cerebral performance category 2 and four in category 3 at hospital discharge. The four patients without neurological benefit subsequently died in the ICU. The occurrence of NCSE after open cardiac surgery is significant and frequently associated with brain injury. It seems prudent to perform EEG studies early to interrupt seizure activity and mitigate secondary cerebral injury.
When Can an Emergency CTA Be Dispensed with for TIA Patients?
Authors: Altenbernd Jens-Christian , Gramada Razvan , Kessler Eugen , Skatulla Jakob , Geppert Eduard , Eyding Jens , Nordmeyer Hannes
Published: September 2022

Background: Transient ischemic attacks (TIAs) and minor strokes are often precursors of a major stroke. Therefore, diagnostic work-up of the TIA is essential to reduce the patient’s risk of further ischemic events. Purpose: With the help of this retrospective study, we aim to determine for which TIA patients a CT angiography (CTA) is not immediately necessary in order to reduce radiation exposure and nephrotoxicity. Material and Methods: Clinical and imaging data from patients who presented as an emergency case with a suspected diagnosis of TIA at a teaching hospital between January 2016 and December 2021 were evaluated. The included 1526 patients were divided into two groups—group 1, with major pathologic vascular findings in the CTA, and group 2, with minor vascular pathologies. Results: Out of 1821 patients with suspected TIA on admission, 1526 met the inclusion criteria. In total, 336 (22%) had major vascular pathologies on CTA, and 1190 (78%) were unremarkable. The majority of patients with major vascular pathologies were male and had a history of arterial hypertension, coronary heart disease, myocardial infarction, ischemic stroke, TIA, atherosclerotic peripheral vascular disease, smoking, antiplatelet medication, had a lower duration of TIA symptoms, and had lower ABCD2 scores. Conclusions: We were able to demonstrate a direct correlation between major CTA pathologies and a history of smoking, age, hyperlipidemia, history of peripheral arterial disease, and a history of stroke and TIA. We were able to prove that the ABCD2 score is even reciprocal to CTA pathology. This means that TIA patients without described risk factors do not immediately require a CTA and could be clarified in the course of treatment with ultrasound or MRI.