bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Steroid and Triterpenoid Metabolism in Calendula officinalis Plants and Hairy Root Cultures Exposed to Cadmium Stress
Authors: Rogowska Agata , Pączkowski Cezary , Szakiel Anna
Published: May 2022

The present study investigated the changes in the content of steroids and triterpenoids in C. officinalis hairy root cultures and plants exposed to cadmium stress. The observed effects included the content and composition of analyzed groups of compounds, particularly the proportions among individual sterols (e.g., stigmasterol-to-sitosterol ratio), their ester and glycoside conjugates. The total sterol content increased in roots (by 30%) and hairy root culture (by 44%), whereas it decreased in shoots (by 15%); moreover, these effects were inversely correlated with Cd-induced growth suppression. Metabolic alterations of sterols and their forms seemed to play a greater role in the response to Cd stress in roots than in shoots. The symptoms of the competition between general metabolites (sterols) and specialized metabolites (triterpenoids) were also observed, i.e., the increase of the sterol biosynthesis parallel to the decrease of the triterpenoid content in C. officinalis plant roots and hairy root culture, and the inverse phenomenon in shoots. The similarity of the metabolic modifications observed in the present study on C. officinalis plant roots and hairy roots confirmed the possibility of application of plant in vitro cultures in initial studies for physiological research on plant response to environmental stresses.
Clinical and Genetic Characterization of Patients with Bartter and Gitelman Syndrome
Authors: Palazzo Viviana , Raglianti Valentina , Landini Samuela , Cirillo Luigi , Errichiello Carmela , Buti Elisa , Artuso Rosangela , Tiberi Lucia , Vergani Debora , Dirupo Elia , Romagnani Paola , Mazzinghi Benedetta , Becherucci Francesca
Published: May 2022

Bartter (BS) and Gitelman (GS) syndrome are autosomal recessive inherited tubulopathies, whose clinical diagnosis can be challenging, due to rarity and phenotypic overlap. Genotype–phenotype correlations have important implications in defining kidney and global outcomes. The aim of our study was to assess the diagnostic rate of whole-exome sequencing (WES) coupled with a bioinformatic analysis of copy number variations in a population of 63 patients with BS and GS from a single institution, and to explore genotype-phenotype correlations. We obtained a diagnostic yield of 86% (54/63 patients), allowing disease reclassification in about 14% of patients. Although some clinical and laboratory features were more commonly reported in patients with BS or GS, a significant overlap does exist, and age at onset, preterm birth, gestational age and nephro-calcinosis are frequently misleading. Finally, chronic kidney disease (CKD) occurs in about 30% of patients with BS or GS, suggesting that the long-term prognosis can be unfavorable. In our cohort the features associated with CKD were lower gestational age at birth and a molecular diagnosis of BS, especially BS type 1. The results of our study demonstrate that WES is useful in dealing with the phenotypic heterogeneity of these disorders, improving differential diagnosis and genotype-phenotype correlation.
Exploring Nearest Neighbor Interactions and Their Influence on the Gibbs Energy Landscape of Unfolded Proteins and Peptides
Authors: Schweitzer-Stenner Reinhard
Published: May 2022

The Flory isolated pair hypothesis (IPH) is one of the corner stones of the random coil model, which is generally invoked to describe the conformational dynamics of unfolded and intrinsically disordered proteins (IDPs). It stipulates, that individual residues sample the entire sterically allowed space of the Ramachandran plot without exhibiting any correlations with the conformational dynamics of its neighbors. However, multiple lines of computational, bioinformatic and experimental evidence suggest that nearest neighbors have a significant influence on the conformational sampling of amino acid residues. This implies that the conformational entropy of unfolded polypeptides and proteins is much less than one would expect based on the Ramachandran plots of individual residues. A further implication is that the Gibbs energies of residues in unfolded proteins or polypeptides are not additive. This review provides an overview of what is currently known and what has yet to be explored regarding nearest neighbor interactions in unfolded proteins.
Sp7 Action in the Skeleton: Its Mode of Action, Functions, and Relevance to Skeletal Diseases
Authors: Hojo Hironori , Ohba Shinsuke
Published: May 2022

Osteoblast differentiation is a tightly regulated process in which key transcription factors (TFs) and their target genes constitute gene regulatory networks (GRNs) under the control of osteogenic signaling pathways. Among these TFs, Sp7 works as an osteoblast determinant critical for osteoblast differentiation. Following the identification of Sp7 and a large number of its functional studies, recent genome-scale analyses have made a major contribution to the identification of a “non-canonical” mode of Sp7 action as well as “canonical” ones. The analyses have not only confirmed known Sp7 targets but have also uncovered its additional targets and upstream factors. In addition, biochemical analyses have demonstrated that Sp7 actions are regulated by chemical modifications and protein–protein interaction with other transcriptional regulators. Sp7 is also involved in chondrocyte differentiation and osteocyte biology as well as postnatal bone metabolism. The critical role of SP7 in the skeleton is supported by its relevance to human skeletal diseases. This review aims to overview the Sp7 actions in skeletal development and maintenance, particularly focusing on recent advances in our understanding of how Sp7 functions in the skeleton under physiological and pathological conditions.
TNF-α Induces Mitophagy in Rheumatoid Arthritis Synovial Fibroblasts, and Mitophagy Inhibition Alleviates Synovitis in Collagen Antibody-Induced Arthritis
Authors: Nam Ji-Hee , Lee Jun-Ho , Choi Hyun-Ji , Choi So-Yeon , Noh Kyung-Eun , Jung Nam-Chul , Song Jie-Young , Choi Jinjung , Seo Han Geuk , Jung Sang Youn , Lim Dae-Seog
Published: May 2022

Mitophagy is a selective form of autophagy that removes damaged mitochondria. Increasing evidence indicates that dysregulated mitophagy is implicated in numerous autoimmune diseases, but the role of mitophagy in rheumatoid arthritis (RA) has not yet been reported. The aim of the present study was to determine the roles of mitophagy in patient-derived RA synovial fibroblasts (RASFs) and in the collagen antibody-induced arthritis mouse model. We measured the mitophagy marker PTEN-induced putative kinase 1 (PINK1) in RASFs treated with tumor necrosis factor-α (TNF-α) using Western blotting and immunofluorescence. Arthritis was induced in PINK1−/− mice by intraperitoneal injection of an anti-type II collagen antibody cocktail and lipopolysaccharide. RA severity was assessed by histopathology. PINK1 expression and damaged mitochondria increased in TNF-α treated RASFs via increased intracellular levels of reactive oxygen species. PINK1 knockdown RASFs decreased cellular migration and invasion functions. In addition, PINK1−/− mice with arthritis exhibited markedly reduced swelling and inflammation relative to wild-type mice with arthritis. Taken together, these findings suggest that regulation of PINK1 expression in RA could represent a potential therapeutic and diagnostic target for RA.
Proteomics and Extracellular Vesicles as Novel Biomarker Sources in Peritoneal Dialysis in Children
Authors: Trincianti Chiara , Meleca Vincenzo , La Porta Edoardo , Bruschi Maurizio , Candiano Giovanni , Garbarino Andrea , Kajana Xhuliana , Preda Alberto , Lugani Francesca , Ghiggeri Gian Marco , Angeletti Andrea , Esposito Pasquale , Verrina Enrico
Published: May 2022

Peritoneal dialysis (PD) represents the dialysis modality of choice for pediatric patients with end-stage kidney disease. Indeed, compared with hemodialysis (HD), it offers many advantages, including more flexibility, reduction of the risk of hospital-acquired infections, preservation of residual kidney function, and a better quality of life. However, despite these positive aspects, PD may be associated with several long-term complications that may impair both patient’s general health and PD adequacy. In this view, chronic inflammation, caused by different factors, has a detrimental impact on the structure and function of the peritoneal membrane, leading to sclerosis and consequent PD failure both in adults and children. Although several studies investigated the complex pathogenic pathways underlying peritoneal membrane alterations, these processes remain still to explore. Understanding these mechanisms may provide novel approaches to improve the clinical outcome of pediatric PD patients through the identification of subjects at high risk of complications and the implementation of personalized interventions. In this review, we discuss the main experimental and clinical experiences exploring the potentiality of the proteomic analysis of peritoneal fluids and extracellular vesicles as a source of novel biomarkers in pediatric peritoneal dialysis.
Photopharmacology of Antimitotic Agents
Authors: Kirchner Susanne , Pianowski Zbigniew
Published: May 2022

Antimitotic agents such as the clinically approved vinca alkaloids, taxanes and epothilone can arrest cell growth during interphase and are therefore among the most important drugs available for treating cancer. These agents suppress microtubule dynamics and thus interfere with intracellular transport, inhibit cell proliferation and promote cell death. Because these drugs target biological processes that are essential to all cells, they face an additional challenge when compared to most other drug classes. General toxicity can limit the applicable dose and therefore reduce therapeutic benefits. Photopharmacology aims to avoid these side-effects by introducing compounds that can be applied globally to cells in their inactive form, then be selectively induced to bioactivity in targeted cells or tissue during a defined time window. This review discusses photoswitchable analogues of antimitotic agents that have been developed by combining different photoswitchable motifs with microtubule-stabilizing or microtubule-destabilizing agents.
Effects of Drugs Formerly Suggested for COVID-19 Repurposing on Pannexin1 Channels
Authors: Caufriez Anne , Tabernilla Andrés , Van Campenhout Raf , Cooreman Axelle , Leroy Kaat , Sanz Serrano Julen , Kadam Prashant , dos Santos Rodrigues Bruna , Lamouroux Arthur , Ballet Steven , Vinken Mathieu
Published: May 2022

Although many efforts have been made to elucidate the pathogenesis of COVID-19, the underlying mechanisms are yet to be fully uncovered. However, it is known that a dysfunctional immune response and the accompanying uncontrollable inflammation lead to troublesome outcomes in COVID-19 patients. Pannexin1 channels are put forward as interesting drug targets for the treatment of COVID-19 due to their key role in inflammation and their link to other viral infections. In the present study, we selected a panel of drugs previously tested in clinical trials as potential candidates for the treatment of COVID-19 early on in the pandemic, including hydroxychloroquine, chloroquine, azithromycin, dexamethasone, ribavirin, remdesivir, favipiravir, lopinavir, and ritonavir. The effect of the drugs on pannexin1 channels was assessed at a functional level by means of measurement of extracellular ATP release. Immunoblot analysis and real-time quantitative reversetranscription polymerase chain reaction analysis were used to study the potential of the drugs to alter pannexin1 protein and mRNA expression levels, respectively. Favipiravir, hydroxychloroquine, lopinavir, and the combination of lopinavir with ritonavir were found to inhibit pannexin1 channel activity without affecting pannexin1 protein or mRNA levels. Thusthree new inhibitors of pannexin1 channels were identified that, though currently not being used anymore for the treatment of COVID-19 patients, could be potential drug candidates for other pannexin1-related diseases.
Volatiles Accumulation during Young Pomelo (Citrus maxima (Burm.) Merr.) Fruits Development
Authors: Xiang Nan , Zhao Yihan , Zhang Bing , Gu Qiuming , Chen Weiling , Guo Xinbo
Published: May 2022

As widely planted fruits with high nutritional and medical values, pomelos are managed systematically to achieve the largest economic benefits. But the annual shedding of young pomelos, which could be applied as feedstocks for essential oil extraction with their abundant volatiles, leads to a waste of source. The present study selected two commonly planted pomelo (Citrus maxima (Burm.) Merr.) varieties in Southern China, to investigate the volatile profiles during young pomelo fruits development. Combing transcriptomic analysis, this study aimed at identifying the prominent volatile components in young pomelo fruits in order to preferably extract profitable volatiles, as well, increasing the knowledge concerning regulatory roles of transcription factors (TFs) on volatiles accumulation in young pomelos. Totally 29 volatiles were identified, including 14 monoterpenoids and 13 sesquiterpenoids. Diprene was the principal component with the highest amount. Volatiles were generally decreased during fruits development but preferable stages were figured out for volatile collections. 12 and 17 TFs were related to developing time while ERF003 and MYC2 were highly correlated to monoterpenoids. These findings put forward the comprehensive usages of young pomelos and enriched the regulatory roles of TFs on both fruit development and volatiles metabolism.
Human Platelets Contain, Translate, and Secrete Azurocidin; A Novel Effect on Hemostasis
Authors: Aquino-Domínguez Alba Soledad , Acevedo-Sánchez Víctor , Cruz-Hernández Diego Sait , Sánchez-Aparicio Saraí Remedios , Romero-Tlalolini María de los Ángeles , Baltiérrez-Hoyos Rafael , Sánchez-Navarro Luis Manuel , Torres-Aguilar Honorio , Bustos-Arriaga José , Aguilar-Ruiz Sergio Roberto
Published: May 2022

Platelets play a significant role in hemostasis and perform essential immune functions, evidenced by the extensive repertoire of antimicrobial molecules. Currently, there is no clear description of the presence of azurocidin in human platelets. Azurocidin is a 37 kDa cationic protein abundant in neutrophils, with microbicidal, opsonizing, and vascular permeability-inducing activity. Therefore, this work aimed to characterize the content, secretion, translation, and functions of azurocidin in platelets. Our results show the presence of azurocidin mRNA and protein in α-granules of platelet and megakaryoblasts, and stimulation with thrombin, ADP, and LPS leads to the secretion of free azurocidin as well as within extracellular vesicles. In addition, platelets can translate azurocidin in a basal or thrombin-induced manner. Finally, we found that the addition of low concentrations of azurocidin prevents platelet aggregation and activation. In conclusion, we demonstrate that platelets contain, secrete, and translate azurocidin, and this protein may have important implications for hemostasis.
Genome-Wide Association Study Identifies a Rice Panicle Blast Resistance Gene, Pb2, Encoding NLR Protein
Authors: Yu Yao , Ma Lu , Wang Xinying , Zhao Zhi , Wang Wei , Fan Yunxin , Liu Kunquan , Jiang Tingting , Xiong Ziwei , Song Qisheng , Li Changqing , Wang Panting , Ma Wenjing , Xu Huanan , Wang Xinyu , Zhao Zijing , Wang Jianfei , Zhang Hongsheng , Bao Yongmei
Published: May 2022

Rice blast is one of the main diseases in rice and can occur in different rice growth stages. Due to the complicated procedure of panicle blast identification and instability of panicle blast infection influenced by the environment, most cloned rice resistance genes are associated with leaf blast. In this study, a rice panicle blast resistance gene, Pb2, was identified by genome-wide association mapping based on the panicle blast resistance phenotypes of 230 Rice Diversity Panel 1 (RDP1) accessions with 700,000 single-nucleotide polymorphism (SNP) markers. A genome-wide association study identified 18 panicle blast resistance loci (PBRL) within two years, including 9 reported loci and 2 repeated loci (PBRL2 and PBRL13, PBRL10 and PBRL18). Among them, the repeated locus (PBRL10 and PBRL18) was located in chromosome 11. By haplotype and expression analysis, one of the Nucleotide-binding domain and Leucine-rich Repeat (NLR) Pb2 genes was highly conserved in multiple resistant rice cultivars, and its expression was significantly upregulated after rice blast infection. Pb2 encodes a typical NBS-LRR protein with NB-ARC domain and LRR domain. Compared with wild type plants, the transgenic rice of Pb2 showed enhanced resistance to panicle and leaf blast with reduced lesion number. Subcellular localization of Pb2 showed that it is located on plasma membrane, and GUS tissue-staining observation found that Pb2 is highly expressed in grains, leaf tips and stem nodes. The Pb2 transgenic plants showed no difference in agronomic traits with wild type plants. It indicated that Pb2 could be useful for breeding of rice blast resistance.
A Structural Comparison of SARS-CoV-2 Main Protease and Animal Coronaviral Main Protease Reveals Species-Specific Ligand Binding and Dimerization Mechanism
Authors: Ho Chien-Yi , Yu Jia-Xin , Wang Yu-Chuan , Lin Yu-Chuan , Chiu Yi-Fang , Gao Jing-Yan , Lai Shu-Jung , Chen Ming-Jen , Huang Wei-Chien , Tien Ni , Chen Yeh
Published: May 2022

Animal coronaviruses (CoVs) have been identified to be the origin of Severe Acute Respiratory Syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and probably SARS-CoV-2 that cause severe to fatal diseases in humans. Variations of zoonotic coronaviruses pose potential threats to global human beings. To overcome this problem, we focused on the main protease (Mpro), which is an evolutionary conserved viral protein among different coronaviruses. The broad-spectrum anti-coronaviral drug, GC376, was repurposed to target canine coronavirus (CCoV), which causes gastrointestinal infections in dogs. We found that GC376 can efficiently block the protease activity of CCoV Mpro and can thermodynamically stabilize its folding. The structure of CCoV Mpro in complex with GC376 was subsequently determined at 2.75 Å. GC376 reacts with the catalytic residue C144 of CCoV Mpro and forms an (R)- or (S)-configuration of hemithioacetal. A structural comparison of CCoV Mpro and other animal CoV Mpros with SARS-CoV-2 Mpro revealed three important structural determinants in a substrate-binding pocket that dictate entry and release of substrates. As compared with the conserved A141 of the S1 site and P188 of the S4 site in animal coronaviral Mpros, SARS-CoV-2 Mpro contains N142 and Q189 at equivalent positions which are considered to be more catalytically compatible. Furthermore, the conserved loop with residues 46–49 in animal coronaviral Mpros has been replaced by a stable α-helix in SARS-CoV-2 Mpro. In addition, the species-specific dimerization interface also influences the catalytic efficiency of CoV Mpros. Conclusively, the structural information of this study provides mechanistic insights into the ligand binding and dimerization of CoV Mpros among different species.
Epigenetic Silencing of PTEN and Epi-Transcriptional Silencing of MDM2 Underlied Progression to Secondary Acute Myeloid Leukemia in Myelodysplastic Syndrome Treated with Hypomethylating Agents
Authors: Lee Paul , Yim Rita , Miu Kai-Kei , Fung Sin-Hang , Liao Jason Jinyue , Wang Zhangting , Li Jun , Yung Yammy , Chu Hiu-Tung , Yip Pui-Kwan , Lee Emily , Tse Eric , Kwong Yok-Lam , Gill Harinder
Published: May 2022

In myelodysplastic syndrome (MDS), resistance to hypomethylating agents (HMA) portends a poor prognosis, underscoring the importance of understanding the molecular mechanisms leading to HMA-resistance. In this study, P39 and Kasumi-1 cells and their azacitidine-resistant and decitabine-resistant sublines were evaluated comparatively with transcriptomic and methylomic analyses. Expression profiling and genome-wide methylation microarray showed downregulation of PTEN associated with DNA hypermethylation in P39 cell lines resistant to azacitidine and decitabine. This pattern of PTEN dysregulation was also confirmed in a cohort of patients failing treatment with HMA. DNA hypomethylation of MDM2 was detected with downregulation of MDM2 in HMA resistant cell lines. Long-read sequencing revealed significant RNA hypomethylation of MDM2 resulting in alternative splicing and production of a truncated MDM2 transcript in azacitidine-resistant P39 cells. The expression of this MDM2 truncated transcript was also significantly increased in HMA-resistant patients compared with HMA-responsive patients. In conclusion, epigenetic and epi-transcriptomic dysregulation of PTEN and MDM2 were associated with resistance to hypomethylating agents.
More Worker Capped Brood and Honey Bees with Less Varroa Load Are Simple Precursors of Colony Productivity at Beekeepers’ Disposal: An Extensive Longitudinal Survey
Authors: Kretzschmar Andre , Maisonnasse Alban
Published: May 2022

In response to the concerns of beekeepers on the decline of honey bee populations on lavender honey flow in the lavender fields of southeast France and the consequent decrease of honey production, our long-term survey (2009–2021) monitored the total weight gain collected by these colonies. This study shows the variations in the total weight gain according to regions, years, populations structure (bee number and quantity of capped brood) and Varroa load. Among these factors, years and regions support one third of the variations over this 13-year survey. At the beginning of the honey flow, capped brood is more important than the number of bees, whereas Varroa load severely limits the performance of the colonies. A threshold of 3 mites/100 bees seems to reflect the upper limit of the Varroa load below which the total weight gain is not affected. This survey provides useful information for the beekeepers to better prepare the colonies for this honey flow and allows them to compare their results obtained with our general description of the total weight gains by year.
Patent Landscape of Composting Technology: A Review
Authors: Azis Fatin Amanina , Rijal Masrur , Suhaimi Hazwani , Abas Pg Emeroylariffion
Published: May 2022

Organic waste management is a major global challenge. It accounts for a significant portion of waste that ends up in landfills, where it gradually decomposes and emits methane, a harmful greenhouse gas. Composting is an effective method for potentially solving the problem by converting organic waste into valuable compost. Despite many studies focusing on the composting process, no study has reviewed the technological advancements in the composting fields from the perspective of patents. This review paper begins with background information on the composting process, specifically important factors affecting the process, problems associated with it, and the available technologies to facilitate the process. Different technologies are discussed, ranging from manual to automated methods. Subsequently, 457 patents are selected, classified into different categories, and reviewed in detail, providing a patent technology landscape of composting technology. Automatic composters are more prominent than manual ones as managing organic waste at the source has become more crucial in recent years. The need for a domestic composter creates an opportunity for the development of a compact and automated system for organic waste management, which is more suitable for urbanized settings. This technology has the potential to reduce the amount of organic waste that needs to be managed at an already overburdened landfill, as well as the environmental consequences associated with it.
Association of Oxidized Low-Density Lipoprotein in Nonalcoholic Fatty Liver Disease with High-Risk Plaque on Coronary Computed Tomography Angiography: A Matched Case–Control Study
Authors: Nishihara Takahiro , Miyoshi Toru , Ichikawa Keishi , Osawa Kazuhiro , Nakashima Mitsutaka , Miki Takashi , Ito Hiroshi
Published: May 2022

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for the development of atherosclerotic cardiovascular diseases (CVDs), and oxidative stress has been proposed as a shared pathophysiological condition. This study examined whether oxidized low-density lipoprotein (LDL) is involved in the underlying mechanism that links coronary atherosclerosis and NAFLD. This study included 631 patients who underwent coronary computed tomography angiography (CTA) for suspected coronary artery disease. NAFLD was defined on CT images as a liver-to-spleen attenuation ratio of <1.0. Serum-malondialdehyde-modified LDL (MDA-LDL) and coronary CTA findings were analyzed in a propensity-score-matched cohort of patients with NAFLD (n = 150) and those without NAFLD (n = 150). This study analyzed 300 patients (median age, 65 years; 64% men). Patients with NAFLD had higher MDA-LDL levels and a greater presence of CTA-verified high-risk plaques than those without NAFLD. In the multivariate linear regression analysis, MDA-LDL was independently associated with NAFLD (β = 11.337, p = 0.005) and high-risk plaques (β = 12.487, p = 0.007). Increased MDA-LDL may be a mediator between NAFLD and high-risk coronary plaque on coronary CTA. Increased oxidative stress in NAFLD, as assessed using MDA-LDL, may be involved in the development of CVDs.
Transcranial Direct Current Stimulation as an Approach to Mitigate Neurodevelopmental Disorders Affecting Excitation/Inhibition Balance: Focus on Autism Spectrum Disorder, Schizophrenia, and Attention Deficit/Hyperactivity Disorder
Authors: Sousa Beatriz , Martins João , Castelo-Branco Miguel , Gonçalves Joana
Published: May 2022

Transcranial direct current stimulation (tDCS) has been proposed as a promising therapy for rehabilitation of neurodevelopmental disorders. In this review, we discuss studies on the impact of tDCS as a therapy for autism, schizophrenia, and attention deficit/hyperactivity disorder, as well as the tDCS’ mechanism of action, and propose future paths of research to optimize tDCS treatment protocols. The mechanism underlying tDCS effects is the modulation of excitatory and/or inhibitory activity, making it a valuable tool for restoring the excitation/inhibition (E/I) balance which is disrupted in many neurodevelopmental disorders. Clinical studies have shown that tDCS therapy is well-tolerated by patients and seems to ameliorate behavior and cognitive functions. Alterations in early development of neuronal circuits lead to disruptions in brain activity in neurodevelopmental disorders. An increasing amount of research into the effects of tDCS on neuronal activity has provided a foundation for its use as a therapy for behavior and cognitive characteristics of neurodevelopmental disorders. Clinical studies show that tDCS appears to ameliorate behavioral and cognitive outcomes of patients with autism, schizophrenia, and attention deficit/hyperactivity disorder. More research is needed to understand the mechanisms of action of tDCS and to optimize treatment protocols.
Nutrition Assessment and Management in Patients with Cirrhosis and Cognitive Impairment: A Comprehensive Review of Literature
Authors: Faccioli Jessica , Nardelli Silvia , Gioia Stefania , Riggio Oliviero , Ridola Lorenzo
Published: May 2022

Hepatic encephalopathy (HE) represents a common complication of liver cirrhosis. Protein-calorie malnutrition is frequently encountered in the cirrhotic patient and its most obvious clinical manifestation is sarcopenia. This condition represents a risk factor for HE occurrence because skeletal muscle acts as an alternative site for ammonium detoxification. Preventive intervention through an adequate assessment of nutritional status should be carried out at early stages of the disease and in a multidisciplinary team using both non-instrumental methods (food diary, anthropometric measurements, blood chemistry tests) and instrumental methods (bioimpedance testing, DEXA, CT, indirect calorimetry, dynamometry). Dietary recommendations for patients with HE do not differ from those for cirrhotic patient without HE. Daily caloric intake in the non-obese patient should be 30–40 Kcal/Kg/day with a protein intake of 1–1.5 g/Kg/day, especially of vegetable origin, through 4–6 meals daily. In patients with HE, it is also essential to monitor electrolyte balance, supplementing any micronutrient deficiencies such as sodium and zinc, as well as vitamin deficiencies because they can cause neurological symptoms similar to those of HE. In light of the critical role of nutritional status, this aspect should not be underestimated and should be included in the diagnostic–therapeutic algorithm of patients with HE.
Simple Predictors for Cardiac Fibrosis in Patients with Type 2 Diabetes Mellitus: The Role of Circulating Biomarkers and Pulse Wave Velocity
Authors: Luneva Ekaterina B. , Vasileva Anastasia A. , Karelkina Elena V. , Boyarinova Maria A. , Mikhaylov Evgeny N. , Ryzhkov Anton V. , Babenko Alina Y. , Konradi Alexandra O. , Moiseeva Olga M.
Published: May 2022

Cardiac fibrosis is the basis of structural and functional disorders in patients with diabetes mellitus (T2DM). A wide range of laboratory and instrumental methods is used for its prediction. The study aimed to identify simple predictors of cardiac fibrosis in patients with T2DM based on the analysis of circulating fibrosis biomarkers and arterial stiffness. The study included patients with T2DM (n = 37) and cardiovascular risk factors (RF, n = 27) who underwent ECHO, cardiac magnetic resonance imaging (MRI), pulse wave analysis (PWV), reactive hyperemia (RH), peripheral arterial tonometry, carotid ultrasonography, and assessment of serum fibrosis biomarkers. As a control group, 15 healthy subjects were examined. Left ventricular concentric hypertrophy was accompanied by an increased serum galectin-3 level in T2DM patients. There was a relationship between the PICP and HbA1c levels in both main groups (R2 = 0.309; p = 0.014). A negative correlation between PICP level and the global longitudinal strain (GLS) was found (r = −0.467; p = 0.004). The RH index had a negative correlation with the duration of diabetes (r = −0.356; p = 0.03), the carotid-femoral PWV (r = −0.371; p = 0.024), and the carotid intima-media thickness (r = −0.622; p < 0.001). The late gadolinium-enhanced (LGE) cardiac MRI was detected in 22 (59.5%) T2DM and in 4 (14.85%) RF patients. Diabetes, its baseline treatment with metformin, HbA1c and serum TIMP-1 levels, and left ventricle hypertrophy had moderate positive correlations with LGE findings (p < 0.05). Using the multivariate regression analysis, increased TIMP-1 level was identified as an independent factor associated with cardiac fibrosis.
The Impact of Steep Trendelenburg Position on Intraocular Pressure
Authors: Ripa Matteo , Schipa Chiara , Kopsacheilis Nikolaos , Nomikarios Mikes , Perrotta Gerardo , De Rosa Carlo , Aceto Paola , Sollazzi Liliana , De Rosa Pasquale , Motta Lorenzo
Published: May 2022

Intraocular pressure occurring during the Trendelenburg position may be a risk for postoperative visual loss and other ocular complications. Intraocular pressure (IOP) higher than 21 mmHg poses a risk for ocular impairment causing several conditions such as glaucoma, detached retina, and postoperative vision loss. Many factors might play a role in IOP increase, like peak expiratory pressure (PIP), mean arterial blood pressure (MAP), end-tidal CO2 (ETCO2) and surgical duration and some others (anaesthetic and neuromuscular blockade depth) contribute by reducing IOP during procedures requiring both pneumoperitoneum and steep Trendelenburg position (25–45° head-down tilt). Despite transient visual field loss after surgery, no signs of ischemia or changes to the retinal nerve fibre layer (RNFL) have been shown after surgery. Over the years, several studies have been conducted to control and prevent IOPs intraoperative increase. Multiple strategies have been proposed by different authors over the years to reduce IOP during laparoscopic procedures, especially those involving steep Trendelenburg positions such as robot-assisted laparoscopic prostatectomy (RALP), and abdominal and pelvic procedures. These strategies included both positional and pharmacological strategies.
What the Body Reveals about Lay Knowledge of Psychological Flexibility
Authors: Falletta-Cowden Neal , Smith Patrick , Hayes Steven C. , Georgescu Sandra , Kolahdouzan Seyed Ali
Published: May 2022

The embodied knowledge of psychological flexibility processes was tested by examining the ability of raters to score whole body pictures based on the degree to which they were open, aware, and engaged. Participants’ best and worst physical posture was photographed when asked to think of a difficult psychological matter. Naïve and untrained raters (n = 16) showed excellent reliability while rating the postures of 82 persons from the general population in Reno and Chicago in the USA and recent Iranian immigrants in the Maryland/DC area. Participants showed embodied knowledge of psychological flexibility concepts across all three locations (though significantly less among those recently from Iran). Thus, experience alone appears to teach people that psychological flexibility is helpful, even if they are unable to express this knowledge in words. Implications for psychotherapeutic work is considered.
Osteolytic vs. Osteoblastic Metastatic Lesion: Computational Modeling of the Mechanical Behavior in the Human Vertebra after Screws Fixation Procedure
Authors: Bianchi Daniele , Falcinelli Cristina , Molinari Leonardo , Gizzi Alessio , Di Martino Alberto
Published: May 2022

Metastatic lesions compromise the mechanical integrity of vertebrae, increasing the fracture risk. Screw fixation is usually performed to guarantee spinal stability and prevent dramatic fracture events. Accordingly, predicting the overall mechanical response in such conditions is critical to planning and optimizing surgical treatment. This work proposes an image-based finite element computational approach describing the mechanical behavior of a patient-specific instrumented metastatic vertebra by assessing the effect of lesion size, location, type, and shape on the fracture load and fracture patterns under physiological loading conditions. A specific constitutive model for metastasis is integrated to account for the effect of the diseased tissue on the bone material properties. Computational results demonstrate that size, location, and type of metastasis significantly affect the overall vertebral mechanical response and suggest a better way to account for these parameters in estimating the fracture risk. Combining multiple osteolytic lesions to account for the irregular shape of the overall metastatic tissue does not significantly affect the vertebra fracture load. In addition, the combination of loading mode and metastasis type is shown for the first time as a critical modeling parameter in determining fracture risk. The proposed computational approach moves toward defining a clinically integrated tool to improve the management of metastatic vertebrae and quantitatively evaluate fracture risk.
Growth Pattern of Hepatic Metastasis as a Prognostic Index Reflecting Liver Metastasis-Associated Survival in Breast Cancer Liver Metastasis
Authors: Lee Jieun , Choi Moonhyung , Joe Seungyeon , Shin Kabsoo , Lee Sung-Hak , Lee Ahwon
Published: May 2022

Breast cancer with liver metastasis (BCLM) frequently cause hepatic failure owing to extensive liver metastasis compared to other cancers; however, there are no clinicopathologic or radiologic parameters for estimating BCLM prognosis. We analyzed the relationship between radiologic and clinicopathologic characteristics with survival outcomes in BCLM. During 2009–2019, baseline and final abdomen computed tomography or liver magnetic resonance imaging of BCLM patients were reviewed. Liver metastasis patterns were classified as oligometastasis (≤3 metastatic lesions), non-confluent or confluent mass formation, infiltration, and pseudocirrhosis. Thirty-one surgical or biopsy specimens for liver metastasis were immunostained for L1 adhesion molecule (L1CAM), Yes-associated protein 1/Transcriptional co-activator with PDZ-binding motif (YAP/TAZ), and β1-integrin. Out of 156 patients, 77 initially had oligometastasis, 58 had nonconfluent mass formation, 14 had confluent mass formation, and 7 had infiltrative liver metastasis. Confluent or infiltrative liver metastasis showed inferior liver metastasis-associated survival (LMOS) compared to others (p = 0.001). Positive staining for L1CAM and YAP/TAZ was associated with inferior survival, and YAP/TAZ was related to final liver metastasis. Initial hepatic metastasis was associated with LMOS, especially confluent mass formation, and infiltrative liver metastasis pattern was associated with poor survival. Positive staining for YAP/TAZ and L1CAM was associated with inferior LMOS, and YAP/TAZ was related to final liver metastasis.
A Review of the Immunologic Pathways Involved in Bullous Pemphigoid and Novel Therapeutic Targets
Authors: Afarideh Mohsen , Borucki Robert , Werth Victoria P.
Published: May 2022

Bullous pemphigoid (BP) is a rare, chronic antibody-mediated autoimmune blistering disease primarily affecting the elderly, with an age of onset over 60. Current treatment options are limited and involve the use of corticosteroids and immunosuppressants, but their long-term use is associated with significant morbidity and mortality. In Japan, human intravenous immunoglobin is approved for the treatment of corticosteroid-refractory BP. However, no treatment option is approved by the Food and Drug Administration for the management of BP. Therefore, developing effective therapies free of debilitating side effects is imperative. In this review, we summarize the main immunologic pathways involved in the pathogenesis of BP, with an emphasis on the role of eosinophils, immunoglobulins, cytokines such as the interleukin (IL)-4 and IL-5, and complements. We further discuss the latest advances with novel therapeutic targets tested for the management of BP. Ongoing efforts are needed to run well-designed controlled trials and test the efficacy and safety of investigational drugs while providing much-needed access to these medications for refractory patients who will not otherwise be able to afford them as off-label prescriptions.
An Improved Framework of Marine Major Function-Oriented Zoning in Advancing Ecosystem-Based Management
Authors: Lin Yanhong , Huang Faming , Zhang Yang , Wang Qi , Huang Jinliang , Chen Qiuming , Xue Xiongzhi
Published: May 2022

Planning and zoning of marine areas is a common practice worldwide. In China, marine major function-oriented zoning (MMFOZ) is an effective geographical method for ensuring sustainable marine resource and ecosystems development; however, ecosystem-based management (EBM) has neither been considered in MMFOZ research nor in practice. Thus, the current MMFOZ evaluation system does not consider integration between the terrestrial and marine components, and the administrative boundaries are adopted as those of research areas and spatial zoning units. Here, an improved MMFOZ framework is presented through an ecosystem-based delimitation of the research area and subregions and a novel indicator system integrating land- and sea-based impacts, to assess and discriminate MMFOZ. A bay ecosystem and nearby land catchment units were selected as the research object. The results revealed two marine optimized development zones, one marine significant development zone, and six marine restricted development zones were divided, with areas of 358.11 km2 (24.63% of the total zoning area), 605.95 km2 (41.69%), and 489.54 km2 (33.68%), respectively. The improved MMFOZ framework coupled with EBM effectively addressed the limitations of marine spatial planning (MSP), while providing a new practical tool for a novel paradigm of sea governance based on an EBM–MSP coupling framework.
First Estimates of Age and Growth of the Lusitanian Cownose Ray (Rhinoptera marginata) from the Mediterranean Sea
Authors: Başusta Nuri , Başusta Asiye , Çiçek Erdoğan , Cicia Angela M. , Sulikowski James A.
Published: May 2022

Within the eastern Mediterranean, increased fishing pressure coupled with a lack of basic biological information is threatening the sustainability of the rare Lusitanian cownose ray (Rhinoptera marginata). To provide baseline life-history data for this species, age estimates were obtained from vertebral band counts of 224 rays (size range: 210–998 mm disc width and 140 to 13,600 g weight) collected from Iskenderun Bay. Females ranged in size from 210 to 998 mm disc width and 238 to 13,600 g weight, while males ranged from 130 to 866 mm disc width and 140 to 8250 g weight. The index of average percent error (2.8%) and age-bias plot suggest that the aging method used represents a precise and non-biased approach. Marginal increment analysis indicated that a single opaque band is deposited annually between August and September. The oldest ages obtained for R. marginata were 9 years for males and 19 years for females, which corresponded to total lengths of 866 and 998 mm disc width, respectively. For males, limited samples prevented the accurate calculation of growth rates; however, for combined sexes, observed and disc width-at-age data resulted in the following von Bertalanffy growth parameters: DW∞ = 1102.16 mm, k = 0.148 and t0 = −0.2167. Although additional samples are necessary to determine growth rates in males, the results of the present study indicate that R. marginata females exhibit life history characteristics similar to other Rhinoptera species.
Quantifying Background Magnetic Fields at Marine Energy Sites: Challenges and Recommendations
Authors: Grear Molly E. , McVey James R. , Cotter Emma D. , Williams Nolann G. , Cavagnaro Robert J.
Published: May 2022

Unknowns around the environmental effects of marine renewable energy have slowed the deployment of this emerging technology worldwide. Established testing methods are necessary to safely permit and develop marine energy devices. Magnetic fields are one potential cause of environmental effects and are created when electricity is generated and transmitted to shore. Further, the existing variation of the background magnetic field at sites that may be developed for marine energy is largely unknown, making it difficult to assess how much additional stress or impact the anthropogenic magnetic field may have. This study investigates two instruments for their ability to characterize the background magnetic fields at a potential marine energy site in Sequim Bay, WA. Based on this evaluation, this study recommends an Overhauser magnetomer for assessing the background magnetic field and demonstrates the use of this sensor at a potential marine energy site.
A Method for Identifying the Key Performance Shaping Factors to Prevent Human Errors during Oil Tanker Offloading Work
Authors: Zhang Renyou , Meng Huixing , Ge Jun , Tan Henry
Published: May 2022

Oil tanker offloading is a human-related and high-risk task. A small operational error may trigger catastrophic accidents such as fire and explosion. It is recognised that more than 70% of industrial accidents are blamed for human errors, so preventing them is crucial. As human error is associated with a variety of Performance Shaping Factors (PSFs), it is meaningful to identify key PSFs for safe operations during oil tanker offloading process. However, some issues are obstacles to finding the crucial PSFs. The recording data of most PSFs are always incomplete and imperfect. Moreover, the standard for ranking PSFs should be rational. In addition, the performance of each PSF at the different stages is oil offloading is usually unstable and may change with time. As a result, this study aims to conduct a method that mainly relies on Grey Relational Analysis (GRA), the definition of “Risk” (combination of likelihood and impact), and Hierarchical Task Analysis (HTA) to find several significant PSFs to prevent human errors. GRA deals with the incomplete and imperfect data; the definition of “Risk” provides a rational basis for ranking PSFs; and HTA gives support for considering the PSFs’ changes at different stages of a task. The proposed approach is tested on a real engineering case of oil tanker offloading work at offshore terminal. The result indicates that the method can be applied to identify key PSFs, which in turn provides recommendations for human error prevention to ensure the safety both on board and at terminal.
Is Hyperdermium Congeneric with Ascopolyporus? Phylogenetic Relationships of Ascopolyporus spp. (Cordycipitaceae, Hypocreales) and a New Genus Neohyperdermium on Scale Insects in Thailand
Authors: Thanakitpipattana Donnaya , Mongkolsamrit Suchada , Khonsanit Artit , Himaman Winanda , Luangsa-ard Janet Jennifer , Pornputtapong Natapol
Published: May 2022

During surveys of insect pathogenic fungi (IPF) in Thailand, fungi associated with scale insects and plants were found to represent five new species of the genus Ascopolyporus in Cordycipitaceae. Their macroscopic features resembled both Hyperdermium and Ascopolyporus. Morphological comparisons with the type and known Ascopolyporus and Hyperdermium species and phylogenetic evidence from a multigene dataset support the appointment of a new species of Ascopolyporus. Moreover, the data also revealed that the type species of Hyperdermium, H. caulium, is nested within Ascopolyporus, suggesting that Hyperdermium is congeneric with Ascopolyporus. The specimens investigated here differ from other Ascopolyporus species by phenotypic characters including size and color of stromata. Phylogenetic analyses of combined LSU, TEF1, RPB1 and RPB2 sequences strongly support the notion that these strains are distinct from known species of Ascopolyporus, and are proposed as Ascopolyporus albus, A. galloides, A. griseoperitheciatus, A. khaoyaiensis and A. purpuratus. Neohyperdermium gen. nov. is introduced for other species originally assigned to Hyperdermium and Cordyceps occurring on scale insects and host plants as epiphytes, accommodating two new combinations of Hyperdermium pulvinatum and Cordyceps piperis.
Taxonomy, Phylogenetic and Ancestral Area Reconstruction in Phyllachora, with Four Novel Species from Northwestern China
Authors: Li Jin-Chen , Wu Hai-Xia , Li Yuying , Li Xin-Hao , Song Jia-Yu , Suwannarach Nakarin , Wijayawardene Nalin N.
Published: May 2022

The members of Phyllachora are biotrophic, obligate plant parasitic fungi featuring a high degree of host specificity. This genus also features a high degree of species richness and worldwide distribution. In this study, four species occurring on leaf and stem of two different species of grass were collected from Shanxi and Shaanxi Provinces, China. Based on morphological analysis, multigene (combined data set of LSU, SSU, and ITS) phylogenetic analyses (maximum likelihood and Bayesian analysis), and host relationship, we introduce herein four new taxa of Phyllachora. Ancestral area reconstruction analysis showed that the ancestral area of Phyllachora occurred in Latin America about 194 Mya. Novel taxa are compared with the related Phyllachora species. Detailed descriptions, illustrations, and notes are provided for each species.