bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclanilide Induces Lateral Bud Outgrowth by Modulating Cytokinin Biosynthesis and Signalling Pathways in Apple Identified via Transcriptome Analysis
Authors: Ma Juanjuan , Xie Lingling , Zhao Qian , Sun Yiting , Zhang Dong
Published: January 2022

Cyclanilide (CYC), a plant growth regulator, is a potent shoot branching agent in apple. However, its mechanism remains unclear. The current study revealed that CYC treatment resulted in massive reprogramming of the axillary bud transcriptome, implicating several hormones in the response. We observed a marked increase (approximately 2-fold) in the level of zeatin riboside and a significant decrease (approximately 2-fold) in the level of abscisic acid (ABA). Zeatin metabolism gene cytokinin (CTK) oxidase 1 (CKX 1) was down-regulated at 168 h after CYC treatment compared with the control. Weighted gene co-expression network analysis of differentially expressed genes demonstrated the turquoise module clusters exhibited the highest positive correlation with zeatin riboside (r = 0.92) and the highest negative correlation with ABA (r = −0.8). A total of 37 genes were significantly enriched in the plant hormone signal transduction pathway in the turquoise module. Among them, the expressions of CTK receptor genes WOODEN LEG and the CTK type-A response regulators genes ARR3 and ARR9 were up-regulated. ABA signal response genes protein phosphatase 2C genes ABI2 and ABI5 were down-regulated in lateral buds after CYC treatment at 168 h. In addition, exogenous application of 6-benzylaminopurine (6-BA, a synthetic type of CTK) and CYC enhanced the inducing effect of CYC, whereas exogenous application of lovastatin (a synthetic type of inhibitor of CTK biosynthesis) or ABA and CYC weakened the promoting effect of CYC. These results collectively revealed that the stimulation of bud growth by CYC might involve CTK biosynthesis and signalling, including genes CKX1 and ARR3/9, which provided a direction for further study of the branching promoting mechanism of CYC.
Reduced DNAJC3 Expression Affects Protein Translocation across the ER Membrane and Attenuates the Down-Modulating Effect of the Translocation Inhibitor Cyclotriazadisulfonamide
Authors: Pauwels Eva , Provinciael Becky , Camps Anita , Hartmann Enno , Vermeire Kurt
Published: January 2022

One of the reported substrates for the endoplasmic reticulum (ER) translocation inhibitor cyclotriazadisulfonamide (CADA) is DNAJC3, a chaperone of the unfolded protein response during ER stress. In this study, we investigated the impact of altered DNAJC3 protein levels on the inhibitory activity of CADA. By comparing WT DNAJC3 with a CADA-resistant DNAJC3 mutant, we observed the enhanced sensitivity of human CD4, PTK7 and ERLEC1 for CADA when DNAJC3 was expressed at high levels. Combined treatment of CADA with a proteasome inhibitor resulted in synergistic inhibition of protein translocation and in the rescue of a small preprotein fraction, which presumably corresponds to the CADA affected protein fraction that is stalled at the Sec61 translocon. We demonstrate that DNAJC3 enhances the protein translation of a reporter protein that is expressed downstream of the CADA-stalled substrate, suggesting that DNAJC3 promotes the clearance of the clogged translocon. We propose a model in which a reduced DNAJC3 level by CADA slows down the clearance of CADA-stalled substrates. This results in higher residual translocation into the ER lumen due to the longer dwelling time of the temporarily stalled substrates in the translocon. Thus, by directly reducing DNAJC3 protein levels, CADA attenuates its net down-modulating effect on its substrates.
Immune-Enhancing Effect of Submerged Culture of Ceriporia lacerata Mycelia on Cyclophosphamide-Induced Immunosuppressed Mice and the Underlying Mechanisms in Macrophages
Authors: Hwang Yong Pil , Lee Gi Ho , Pham Thi Hoa , Kim Mi Yeon , Kim Chae Yeon , Lee Seung Yeon , Han Eun Hee , Choi Chul Yung , Hwang Seong Deok , Ahn Sunyoung , Jeong Hye Gwang
Published: January 2022

The white-rot fungi Ceriporia lacerata is used in bioremediation, such as lignocellulose degradation, in nature. Submerged cultures and extracts of C. lacerata mycelia (CLM) have been reported to contain various active ingredients, including β-glucan and extracellular polysaccharides, and to exert anti-diabetogenic properties in mice and cell lines. However, the immunostimulatory effects have not yet been reported. This study aimed to identify the immunomodulatory effects, and underlying mechanisms thereof, of submerged cultures of CLM using RAW264.7 macrophages and cyclophosphamide (CTX)-induced immunosuppression in mice. Compared to CTX-induced immunosuppressed mice, the spleen and thymus indexes in mice orally administered CLM were significantly increased; body weight loss was alleviated; and natural killer (NK) cytotoxicity, lymphocyte proliferation, and cytokine (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, and interleukin [IL]-2) production were elevated in the serum. In RAW264.7 macrophages, treatment with CLM induced phagocytic activity, increased the production of nitric oxide (NO), and promoted mRNA expression of the immunomodulatory cytokines TNF-α, IFN-γ, IL-1β, IL-6, IL-10, and IL-12. In addition, CLM increased the inducible NO synthase (iNOS) concentration in macrophages, similar to lipopolysaccharide (LPS) stimulation. Mechanistic studies showed that CLM induced the activation of the NF-κB, PI3k/Akt, ERK1/2, and JNK1/2 pathways. Moreover, the phosphorylation of NF-κB and IκB induced by CLM in RAW264.7 cells was suppressed by specific MAPKs and PI3K inhibitors. Further experiments with a TLR4 inhibitor demonstrated that the production of TNF-α, IL-1β, and IL-6 induced by CLM was decreased after TLR4 was blocked. Overall, CLM protected against CTX-induced adverse reactions by enhancing humoral and cellular immune functions, and has potential as an immunomodulatory agent.
Effect of Humid Air Exposed to IR Radiation on Enzyme Activity
Authors: Yablonskaya Olga I. , Voeikov Vladimir L. , Novikov Kirill N. , Buravleva Ekaterina V. , Menshov Valeriy A. , Trofimov Aleksei V.
Published: January 2022

Water vapor absorbs well in the infra-red region of the electromagnetic spectrum. Absorption of radiant energy by water or water droplets leads to formation of exclusion zone water that possesses peculiar physico-chemical properties. In the course of this study, normally functioning and damaged alkaline phosphatase, horseradish peroxidase and catalase were treated with humid air irradiated with infrared light with a wavelength in the range of 1270 nm and referred to as coherent humidity (CoHu). One-minute long treatment with CoHu helped to partially protect enzymes from heat inactivation, mixed function oxidation, and loss of activity due to partial unfolding. Authors suggest that a possible mechanism underlying the observed effects involves altering the physicochemical properties of aqueous media while treatment of the objects with CoHu where CoHu acts as an intermediary.
Extended Prophylactic Effect of N-tert-Butyl-α-phenylnitron against Oxidative/Nitrosative Damage Caused by the DNA-Hypomethylating Drug 5-Azacytidine in the Rat Placenta
Authors: Sobočan Nikola , Himelreich-Perić Marta , Katušić-Bojanac Ana , Krasić Jure , Sinčić Nino , Majić Željka , Jurić-Lekić Gordana , Šerman Ljiljana , Marić Andreja , Ježek Davor , Bulić-Jakuš Floriana
Published: January 2022

Antioxidant N-tert-Butyl-α-phenylnitron (PBN) partly protected embryos from the negative effects of a DNA demethylating drug 5-azacytidine during pregnancy. Our aim was to investigate PBN’s impact on the placenta. Fischer rat dams were treated on gestation days (GD) 12 and 13 by PBN (40 mg/kg), followed by 5azaC (5 mg/kg) after one hour. Global methylation was assessed by pyrosequencing. Numerical density was calculated from immunohistochemical expression in single cells for proliferating (PCNA), oxidative (oxoguanosine) and nitrosative (nitrotyrosine) activity. Results were compared with the PBN-treated and control rats. PBN-pretreatment significantly increased placental weight at GD15 and GD20, diminished by 5azaC, and diminished apoptosis in GD 20 placentas caused by 5azaC. Oxoguanosine expression in placentas of 5azaC-treated dams was especially high in the placental labyrinth on GD 15, while PBN-pretreatment lowered its expression on GD 15 and GD 20 in both the labyrinth and basal layer. 5azaC enhanced nitrotyrosine level in the labyrinth of both gestational stages, while PBN-pretreatment lowered it. We conclude that PBN exerted its prophylactic activity against DNA hypomethylating agent 5azaC in the placenta through free radical scavenging, especially in the labyrinthine part of the placenta until the last day of pregnancy.
Molecular Evolution of Tubulins in Diatoms
Authors: Khabudaev Kirill V. , Petrova Darya P. , Bedoshvili Yekaterina D. , Likhoshway Yelena V. , Grachev Mikhail A.
Published: January 2022

Microtubules are formed by α- and β-tubulin heterodimers nucleated with γ-tubulin. Tubulins are conserved eukaryotic proteins. Previously, it was shown that microtubules are involved in diatom silica frustule morphogenesis. Diatom frustules are varied, and their morphology is species-specific. Despite the attractiveness of the problem of elucidating the molecular mechanisms of genetically programmed morphogenesis, the structure and evolution of diatom tubulins have not been studied previously. Based on available genomic and transcriptome data, we analyzed the phylogeny of the predicted amino acid sequences of diatom α-, β- and γ-tubulins and identified five groups for α-tubulins, six for β-tubulins and four for γ-tubulins. We identified characteristic amino acids of each of these groups and also analyzed possible posttranslational modification sites of diatom tubulins. According to our results, we assumed what changes occurred in the diatom tubulin structures during their evolution. We also identified which tubulin groups are inherent in large diatom taxa. The similarity between the evolution of diatom tubulins and the evolution of diatoms suggests that molecular changes in α-, β- and γ-tubulins could be one of the factors in the formation of a high morphological diversity of diatoms.
Excited States Computation of Models of Phenylalanine Protein Chains: TD-DFT and Composite CC2/TD-DFT Protocols
Authors: Lebel Marine , Very Thibaut , Gloaguen Eric , Tardivel Benjamin , Mons Michel , Brenner Valérie
Published: January 2022

The present benchmark calculations testify to the validity of time-dependent density functional theory (TD-DFT) when exploring the low-lying excited states potential energy surfaces of models of phenylalanine protein chains. Among three functionals suitable for systems exhibiting charge-transfer excited states, LC-ωPBE, CAM-B3LYP, and ωB97X-D, which were tested on a reference peptide system, we selected the ωB97X-D functional, which gave the best results compared to the approximate coupled-cluster singles and doubles (CC2) method. A quantitative agreement for both the geometrical parameters and the vibrational frequencies was obtained for the lowest singlet excited state (a ππ* state) of the series of capped peptides. In contrast, only a qualitative agreement was met for the corresponding adiabatic zero-point vibrational energy (ZPVE)-corrected excitation energies. Two composite protocols combining CC2 and DFT/TD-DFT methods were then developed to improve these calculations. Both protocols substantially reduced the error compared to CC2 and experiment, and the best of both even led to results of CC2 quality at a lower cost, thus providing a reliable alternative to this method for very large systems.
Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice
Authors: Zhao Xiangli , Hasan Sadaf , Liou Benjamin , Lin Yi , Sun Ying , Liu Chuanju
Published: January 2022

Neurodegenerative diseases are debilitating impairments that affect millions of people worldwide and are characterized by progressive degeneration of structure and function of the central or peripheral nervous system. Effective biomarkers for neurodegenerative diseases can be used to improve the diagnostic workup in the clinic as well as facilitate the development of effective disease-modifying therapies. Progranulin (PGRN) has been reported to be involved in various neurodegenerative disorders. Hence, in the current study we systematically compared the inflammation and accumulation of typical neurodegenerative disease markers in the brain tissue between PGRN knockout (PGRN KO) and wildtype (WT) mice. We found that PGRN deficiency led to significant neuron loss as well as activation of microglia and astrocytes in aged mice. Several characteristic neurodegenerative markers, including α-synuclein, TAR DNA-binding protein 43 (TDP-43), Tau, and β-amyloid, were all accumulated in the brain of PGRN-deficient mice as compared to WT mice. Moreover, higher aggregation of lipofuscin was observed in the brain tissue of PGRN-deficient mice compared with WT mice. In addition, the autophagy was also defective in the brain of PGRN-deficient mice, indicated by the abnormal expression level of autophagy marker LC3-II. Collectively, comprehensive assays support the idea that PGRN plays an important role during the development of neurodegenerative disease, indicating that PGRN might be a useful biomarker for neurodegenerative diseases in clinical settings.
Primary Founder Mutations in the PRKDC Gene Increase Tumor Mutation Load in Colorectal Cancer
Authors: Pálinkás Hajnalka Laura , Pongor Lőrinc , Balajti Máté , Nagy Ádám , Nagy Kinga , Békési Angéla , Bianchini Giampaolo , Vértessy Beáta G. , Győrffy Balázs
Published: January 2022

The clonal composition of a malignant tumor strongly depends on cellular dynamics influenced by the asynchronized loss of DNA repair mechanisms. Here, our aim was to identify founder mutations leading to subsequent boosts in mutation load. The overall mutation burden in 591 colorectal cancer tumors was analyzed, including the mutation status of DNA-repair genes. The number of mutations was first determined across all patients and the proportion of genes having mutation in each percentile was ranked. Early mutations in DNA repair genes preceding a mutational expansion were designated as founder mutations. Survival analysis for gene expression was performed using microarray data with available relapse-free survival. Of the 180 genes involved in DNA repair, the top five founder mutations were in PRKDC (n = 31), ATM (n = 26), POLE (n = 18), SRCAP (n = 18), and BRCA2 (n = 15). PRKDC expression was 6.4-fold higher in tumors compared to normal samples, and higher expression led to longer relapse-free survival in 1211 patients (HR = 0.72, p = 4.4 × 10−3). In an experimental setting, the mutational load resulting from UV radiation combined with inhibition of PRKDC was analyzed. Upon treatments, the mutational load exposed a significant two-fold increase. Our results suggest PRKDC as a new key gene driving tumor heterogeneity.
Bacteriophage-Encoded DNA Polymerases—Beyond the Traditional View of Polymerase Activities
Authors: Morcinek-Orłowska Joanna , Zdrojewska Karolina , Węgrzyn Alicja
Published: January 2022

DNA polymerases are enzymes capable of synthesizing DNA. They are involved in replication of genomes of all cellular organisms as well as in processes of DNA repair and genetic recombination. However, DNA polymerases can also be encoded by viruses, including bacteriophages, and such enzymes are involved in viral DNA replication. DNA synthesizing enzymes are grouped in several families according to their structures and functions. Nevertheless, there are examples of bacteriophage-encoded DNA polymerases which are significantly different from other known enzymes capable of catalyzing synthesis of DNA. These differences are both structural and functional, indicating a huge biodiversity of bacteriophages and specific properties of their enzymes which had to evolve under certain conditions, selecting unusual properties of the enzymes which are nonetheless crucial for survival of these viruses, propagating as special kinds of obligatory parasites. In this review, we present a brief overview on DNA polymerases, and then we discuss unusual properties of different bacteriophage-encoded enzymes, such as those able to initiate DNA synthesis using the protein-priming mechanisms or even start this process without any primer, as well as able to incorporate untypical nucleotides. Apart from being extremely interesting examples of biochemical biodiversity, bacteriophage-encoded DNA polymerases can also be useful tools in genetic engineering and biotechnology.
Apoptosis in Type 2 Diabetes: Can It Be Prevented? Hippo Pathway Prospects
Authors: Kilanowska Agnieszka , Ziółkowska Agnieszka
Published: January 2022

Diabetes mellitus is a heterogeneous disease of complex etiology and pathogenesis. Hyperglycemia leads to many serious complications, but also directly initiates the process of β cell apoptosis. A potential strategy for the preservation of pancreatic β cells in diabetes may be to inhibit the implementation of pro-apoptotic pathways or to enhance the action of pancreatic protective factors. The Hippo signaling pathway is proposed and selected as a target to manipulate the activity of its core proteins in therapy-basic research. MST1 and LATS2, as major upstream signaling kinases of the Hippo pathway, are considered as target candidates for pharmacologically induced tissue regeneration and inhibition of apoptosis. Manipulating the activity of components of the Hippo pathway offers a wide range of possibilities, and thus is a potential tool in the treatment of diabetes and the regeneration of β cells. Therefore, it is important to fully understand the processes involved in apoptosis in diabetic states and completely characterize the role of this pathway in diabetes. Therapy consisting of slowing down or stopping the mechanisms of apoptosis may be an important direction of diabetes treatment in the future.
Diagnostic Accuracy of CT Texture Analysis in Adrenal Masses: A Systematic Review
Authors: Crimì Filippo , Quaia Emilio , Cabrelle Giulio , Zanon Chiara , Pepe Alessia , Regazzo Daniela , Tizianel Irene , Scaroni Carla , Ceccato Filippo
Published: January 2022

Adrenal incidentalomas (AIs) are incidentally discovered adrenal neoplasms. Overt endocrine secretion (glucocorticoids, mineralocorticoids, and catecholamines) and malignancy (primary or metastatic disease) are assessed at baseline evaluation. Size, lipid content, and washout characterise benign AIs (respectively, <4 cm, <10 Hounsfield unit, and rapid release); nonetheless, 30% of adrenal lesions are not correctly indicated. Recently, image-based texture analysis from computed tomography (CT) may be useful to assess the behaviour of indeterminate adrenal lesions. We performed a systematic review to provide the state-of-the-art of texture analysis in patients with AI. We considered 9 papers (from 70 selected), with a median of 125 patients (range 20–356). Histological confirmation was the most used criteria to differentiate benign from the malignant adrenal mass. Unenhanced or contrast-enhanced data were available in all papers; TexRAD and PyRadiomics were the most used software. Four papers analysed the whole volume, and five considered a region of interest. Different texture features were reported, considering first- and second-order statistics. The pooled median area under the ROC curve in all studies was 0.85, depicting a high diagnostic accuracy, up to 93% in differentiating adrenal adenoma from adrenocortical carcinomas. Despite heterogeneous methodology, texture analysis is a promising diagnostic tool in the first assessment of patients with adrenal lesions.
Newborn Screening in Japan—2021
Authors: Tajima Toshihiro
Published: January 2022

Japan’s Newborn Mass Screening (NBS) was started in 1977 for amino acid metabolism disorders (phenylketonuria (PKU), homocystinuria, maple syrup urine, histidineemia (discontinued in 1993)) and galactosemia at the national level as a national project [...]
Characteristics of Trees Infested by the Invasive Primary Wood-Borer Aromia bungii (Coleoptera: Cerambycidae)
Authors: Yamamoto Yuichi , Ishikawa Yosuke , Uehara Kazuhiko
Published: January 2022

The expanding distribution and tree damage of the invasive, primary wood-borer Aromia bungii (Coleoptera: Cerambycidae), which kills trees of the Rosaceae family, is a problem in intruded areas. However, the tree characteristics associated with infestation by A. bungii, which are useful for early detection or prioritizing preventive measures, are not well examined. We investigated the presence or absence of tree damage (response variable) in pre- and post- surveys along with tree characteristics (four explanatory variables; bark roughness, size, species, and vigor) on monitoring trees in uninvaded sites (survey for the first trees to be damaged) and already invaded sites (survey for the next trees to be damaged). We evaluated the variables using generalized linear mixed models for each site (i.e., a first trees model and a next trees model). Three tree characteristics (bark roughness, size, and vigor) were included as explanatory variables in both best models, indicating that trees with rough surface bark, large in size, and weakened conditions were more susceptible to A. bungii infestation. The reasons for the difference between the two models (species was only chosen in the next trees model) will be considered in our future work.
RNAi for Western Corn Rootworm Management: Lessons Learned, Challenges, and Future Directions
Authors: Darlington Molly , Reinders Jordan D. , Sethi Amit , Lu Albert L. , Ramaseshadri Partha , Fischer Joshua R. , Boeckman Chad J. , Petrick Jay S. , Roper Jason M. , Narva Kenneth E. , Vélez Ana M.
Published: January 2022

The western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte, is considered one of the most economically important pests of maize (Zea mays L.) in the United States (U.S.) Corn Belt with costs of management and yield losses exceeding USD ~1–2 billion annually. WCR management has proven challenging given the ability of this insect to evolve resistance to multiple management strategies including synthetic insecticides, cultural practices, and plant-incorporated protectants, generating a constant need to develop new management tools. One of the most recent developments is maize expressing double-stranded hairpin RNA structures targeting housekeeping genes, which triggers an RNA interference (RNAi) response and eventually leads to insect death. Following the first description of in planta RNAi in 2007, traits targeting multiple genes have been explored. In June 2017, the U.S. Environmental Protection Agency approved the first in planta RNAi product against insects for commercial use. This product expresses a dsRNA targeting the WCR snf7 gene in combination with Bt proteins (Cry3Bb1 and Cry34Ab1/Cry35Ab1) to improve trait durability and will be introduced for commercial use in 2022.
Three New Species and One New Record of Hesperoschema (Coleoptera: Staphylinidae: Staphylininae) from China
Authors: Cai Yujie , Tang Liang
Published: January 2022

Three new species: Hesperoschema xuwangi sp. nov. from China (Sichuan), H. bii sp. nov. from China (Xizang), and H. sinicum sp. nov. from China (Guangxi) are described. Hesperoschema malaisei Scheerpeltz, 1965 is new to China (Yunnan), with the male discovered for the first time. The female of H. opacum Schillhammer, 2009 is discovered for the first time. Habitus and diagnostic characteristics of the species treated in this paper were photographed, and a key to species of Hesperoschema Scheerpeltz, 1965 is updated.
Monarchs Reared in Winter in California Are Not Large Enough to Be Migrants. Comment on James et al. First Population Study on Winter Breeding Monarch Butterflies, Danaus plexippus (Lepidoptera: Nymphalidae) in the Urban South Bay of San Francisco, California. Insects 2021, 12, 946
Authors: Davis Andrew K.
Published: January 2022

A recent study in this journal aimed to understand certain changes in the wintering behavior of monarch butterflies, specifically in the western subpopulation of North America [...]
Reply to Davis, A.K. Monarchs Reared in Winter in California Are Not Large Enough to Be Migrants. Comment on “James et al. First Population Study on Winter Breeding Monarch Butterflies, Danaus plexippus (Lepidoptera: Nymphalidae) in the Urban South Bay of San Francisco, California. Insects 2021, 12, 946”
Authors: James David G. , Schaefer Maria C. , Krimmer Easton Karen , Carl Annie
Published: January 2022

This is a reply to the comment from Davis [...]
Xylosandrus crassiusculus (Motschulsky) (Coleoptera: Curculionidae) and Its Fungal Symbiont Ambrosiella roeperi Associated with Arecanut Kernel Decay in Karnataka, India
Authors: Thube Shivaji Hausrao , Pandian Thava Prakasa , Bhavishya Anthara , Babu Merin , Josephrajkumar Arulappan , Chaithra Muddumadiah , Hegde Vinayaka , Ruzzier Enrico
Published: January 2022

Xylosandrus crassiusculus (Coleoptera: Curculionidae: Scolytinae) is reported causing damage to areca palm plantations (Areca catechu L.—Arecaceae) in Karnataka (India). In particular, X. crassiusculus has been observed attacking and successfully reproducing on areca nuts; besides the new host plant record, the data provided here represent the first documented case of spermatophagy for this xyleborine beetle. All infestation symptoms of this polyphagous pest were documented and illustrated. The identity of the scolytid, besides morphologically, was confirmed by its DNA barcoding. Eggs, larvae and pupae were found within the galleries of infested kernels. All galleries of the infested kernels were characterized by the presence of whitish to greyish fungal growth. The fungus was identified as Ambrosiella roeperi, a known symbiont of Xylosandrus crassiusculus. Incidence of this symbiotic insect-fungus complex in the economic part of arecanut, i.e., the kernel, is of serious concern. In a climate change scenario, this beetle with fungal symbionts may pose a serious threat to arecanut production in India and elsewhere.
Spontaneous Bacterial Peritonitis among Cirrhotic Patients: Prevalence, Clinical Characteristics, and Outcomes
Authors: Abu-Freha Naim , Michael Tal , Poupko Liat , Estis-Deaton Asia , Aasla Muhammad , Abu-Freha Omar , Etzion Ohad , Nesher Lior
Published: January 2022

(1) Background: Spontaneous bacterial peritonitis (SBP) is a feared complication of liver cirrhosis. We investigated the prevalence of SBP, positive ascitic fluid cultures, and risk factors for mortality. (2) Methods: A retrospective analysis of all patients with cirrhosis hospitalized or in follow-up in a single center between 1996 and 2020. The clinical data, long-term complications, and mortality of SBP patients were compared with those of non-SBP patients. Ascitic fluid positive culture was compared with those without growth. (3) Results: We included 1035 cirrhotic patients, of which 173 (16.7%) developed SBP. Ascitic fluid culture growth was found in 47.4% of the SBP cases, with Escherichia coli bacteria detected in 38%, 24.4% grew ESBL-producing bacteria, and 14.5% displayed multidrug resistance. In a Cox regression model, SBP, male sex, prolonged INR at diagnosis, and hepatocellular carcinoma were found to be risk factors for mortality in cirrhotic patients. The long-term all-cause mortality was 60% in non-SBP and 90% in SBP patients. (4) Conclusions: Only a minority of cirrhotic patients developed SBP, 47.4% of which had positive ascitic fluid cultures with high antibiotic resistance. Growth of ESBL and multidrug resistant organisms is becoming more frequent in the clinical setting, reaching SBP mortality of 90%.
To Treat or Not to Treat? Polish Physicians’ Opinions about the Clinical Aspects of Cannabinoids—An Online Survey
Authors: Hordowicz Martyna Joanna , Jarosz Jerzy , Klimkiewicz Anna , Czaplińska Małgorzata , Leonhard Agnieszka , Wysocka Maria
Published: January 2022

Introduction: Medical cannabis’ importance in Poland increased dramatically following its legalization as the 12th country in Europe in 2017. However, no studies have been published to give insight into Polish physicians’ opinions about medical cannabis. Objectives: To investigate physician’s opinions about cannabinoids’ utility in clinical practice, concerns regarding their safety profile, and their clinical experience with cannabinoids. Methods: The survey using a self-developed tool was conducted online; participants were physicians with or without specialist training. Participation was voluntary. Physicians were recruited through personal networks, palliative care courses, and Medical Chambers. Results: From June to October 2020, we recruited 173 physicians from 15/16 voivodeships. The largest age group (43.9%; n = 76) was 30–39 year-olds. A similar proportion declared they never used cannabis and did not receive any training regarding cannabinoids (60% for both). Only 15 (8%) ever prescribed medical cannabis, although about 50% declared knowing suitable patients for such therapy, and 53.8% had at least one patient proactively asking for such treatment in the last 6 mo. The most common indication chosen was pain: chronic cancer-related (n = 128), chronic non-cancer (n = 77), and neuropathic (n = 60). Other commonly chosen conditions were alleviation of cancer treatment side-effects (n = 56) and cachexia (n = 57). The overall safety profile of THC was assessed as similar to most commonly used medications, including opioids; NSAIDs and benzodiazepines were, however, perceived as safer. Conclusions: Polish physicians favored the legalization of medical cannabis. However, it is of concern that a limited number have any experience with prescribing cannabis. The creation of clear guidelines to advise physicians in their routine practice and education about pain management and the risks related to the consumption of recreational cannabis for medical conditions are needed.
History of Heart Failure in Patients Hospitalized Due to COVID-19: Relevant Factor of In-Hospital Complications and All-Cause Mortality up to Six Months
Authors: Sokolski Mateusz , Reszka Konrad , Suchocki Tomasz , Adamik Barbara , Doroszko Adrian , Drobnik Jarosław , Gorka-Dynysiewicz Joanna , Jedrzejczyk Maria , Kaliszewski Krzysztof , Kilis-Pstrusinska Katarzyna , Konopska Bogusława , Kopec Agnieszka , Larysz Anna , Lis Weronika , Matera-Witkiewicz Agnieszka , Pawlik-Sobecka Lilla , Rosiek-Biegus Marta , Sokolska Justyna M. , Sokolowski Janusz , Zapolska-Tomasiewicz Anna , Protasiewicz Marcin , Madziarska Katarzyna , Jankowska Ewa A.
Published: January 2022

Background: Patients with heart failure (HF) are at high risk of unfavorable courses of COVID-19. The aim of this study was to evaluate characteristics and outcomes of COVID-19 patients with HF. Methods: Data of patients hospitalized in a tertiary hospital in Poland between March 2020 and May 2021 with laboratory-confirmed COVID-19 were analyzed. The study population was divided into a HF group (patients with a history of HF) and a non-HF group. Results: Out of 2184 patients (65 ± 13 years old, 50% male), 12% had a history of HF. Patients from the HF group were older, more often males, had more comorbidities, more often dyspnea, pulmonary and peripheral congestion, inflammation, and end-organ damage biomarkers. HF patients had longer and more complicated hospital stay, with more frequent acute HF development as compared with non-HF. They had significantly higher mortality assessed in hospital (35% vs. 12%) at three (53% vs. 22%) and six months (72% vs. 47%). Of 76 (4%) patients who developed acute HF, 71% died during hospitalization, 79% at three, and 87% at six months. Conclusions: The history of HF identifies patients with COVID-19 who are at high risk of in-hospital complications and mortality up to six months of follow-up.
Discordant Predictions of Extraglandular Involvement in Primary Sjögren’s Syndrome According to the Anti-SSA/Ro60 Antibodies Detection Assay in a Cohort Study
Authors: Urbanski Geoffrey , Gury Aline , Jeannin Pascale , Chevailler Alain , Lozac’h Pierre , Reynier Pascal , Lavigne Christian , Lacout Carole , Vinatier Emeline
Published: January 2022

Electrophoresis-derived techniques for anti-SSA/Ro60 KDa (anti-SSA) antibodies detection have been progressively replaced by methods using non-native antigens. We aimed to compare the patients’ phenotypes and the occurrence of extraglandular manifestations in primary Sjögren’s syndrome according to the method used to detect anti-SSA antibodies. Sera from patients with a diagnosis of pSS according to ACR/EULAR 2016 criteria between 2008 and 2017 were tested for anti-SSA antibodies using methods with non-native antigens (magnetic bead multiplex assay; line immunoassays) and one with native antigens (counterimmunoelectrophoresis (CIE)). The population was split into three groups according to anti-SSA antibodies status: absence (SSA−), presence in any method except for CIE (SSA+CIE−), and presence in CIE (SSA+CIE+). The patients in the SSA+CIE+ group (n = 70, 42.7%) were ten years younger and presented more immunological activity compared with both the SSA− (n = 80, 48.8%) and SSA+CIE− groups (n = 14, 8.5%). The SSA− and SSA+CIE− groups were poorly distinct. The presence of anti-SSA antibodies solely in CIE was significantly associated with the occurrence of extraglandular manifestations of pSS (HR = 4.45 (2.35–8.42)). Contrary to CIE, methods using non-native antigens to detect anti-SSA antibodies were unable to predict the occurrence of systemic expression of pSS.
Impact of Intravenous Trehalose Administration in Patients with Niemann–Pick Disease Types A and B
Authors: Mobini Moein , Radbakhsh Shabnam , Kubaski Francyne , Eshraghi Peyman , Vakili Saba , Vakili Rahim , Khalili Manijeh , Varesvazirian Majid , Jamialahmadi Tannaz , Alamdaran Seyed , Sayedi Seyed , Rajabi Omid , Emami Seyed , Reiner Željko , Sahebkar Amirhossein
Published: January 2022

Background and Aims: Niemann–Pick disease (NPD) types A (NPA) and B (NPB) are caused by deficiency of the acid sphingomyelinase enzyme, which is encoded by the SMPD1 gene, resulting in progressive pathogenic accumulation of lipids in tissues. Trehalose has been suggested as an autophagy inducer with therapeutic neuroprotective effects. We performed a single-arm, open-label pilot study to assess the potential efficacy of trehalose treatment in patients with NPA and NPB patients. Methods: Five patients with NPD type A and B were enrolled in an open-label, single-arm clinical trial. Trehalose was administrated intravenously (IV) (15 g/week) for three months. The efficacy of trehalose in the management of clinical symptoms was evaluated in patients by assessing the quality of life, serum biomarkers, and high-resolution computed tomography (HRCT) of the lungs at the baseline and end of the interventional trial (day 0 and week 12). Results: The mean of TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients after intervention at W12 compared to the baseline W0, although the difference was not statistically significant. The serum levels of lyso-SM-509 and lyso-SM were decreased in three and four patients out of five, respectively, compared with baseline. Elevated ALT and AST levels were decreased in all patients after 12 weeks of treatment; however, changes were not statistically significant. Pro-oxidant antioxidant balance (PAB) was also decreased and glutathione peroxidase (GPX) activity was increased in serum of patients at the end of the study. Imaging studies of spleen and lung HRCT showed improvement of symptoms in two patients. Conclusions: Positive trends in health-related quality of life (HRQoL), serum biomarkers, and organomegaly were observed after 3 months of treatment with trehalose in patients with NPA and NPB. Although not statistically significant, due to the small number of patients enrolled, these results are encouraging and should be further explored.
Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR
Authors: Young Francis P. , Becker Therese M. , Nimir Mohammed , Opperman Thomas , Chua Wei , Balakrishnar Bavanthi , de Souza Paul , Ma Yafeng
Published: January 2022

Androgen Receptor (AR) alterations (amplification, point mutations, and splice variants) are master players in metastatic castration resistant prostate cancer (CRPC) progression and central therapeutic targets for patient management. Here, we have developed two multiplexed droplet digital PCR (ddPCR) assays to detect AR copy number (CN) and the key point mutation T877A. Overcoming challenges of determining gene amplification from liquid biopsies, these assays cross-validate each other to produce reliable AR amplification and mutation data from plasma cell free DNA (cfDNA) of advanced prostate cancer (PC) patients. Analyzing a mixed PC patient cohort consisting of CRPC and hormone sensitive prostate cancer (HSPC) patients showed that 19% (9/47) patients had AR CN amplification. As expected, only CRPC patients were positive for AR amplification, while interestingly the T877A mutation was identified in two patients still considered HSPC at the time. The ddPCR based analysis of AR alterations in cfDNA is highly economic, feasible, and informative to provide biomarker detection that may help to decide on the best follow-up therapy for CRPC patients.
Risk Factors Associated with Mortality in Severe Chest Trauma Patients Admitted to the ICU
Authors: Barea-Mendoza Jesús Abelardo , Chico-Fernández Mario , Quintana-Díaz Manuel , Pérez-Bárcena Jon , Serviá-Goixart Luís , Molina-Díaz Ismael , Bringas-Bollada María , Ruiz-Aguilar Antonio Luis , Ballesteros-Sanz María Ángeles , Llompart-Pou Juan Antonio ,   on behalf of the Neurointensive Care and Trauma Working Group of the Sociedad Española de Medicina Intensiva Crítica y Unidades Coronarias (SEMICYUC)
Published: January 2022

Our objective was to determine outcomes of severe chest trauma admitted to the ICU and the risk factors associated with mortality. An observational, prospective, and multicenter registry of trauma patients admitted to the participating ICUs (March 2015–December 2019) was utilized to collect the patient data that were analyzed. Severe chest trauma was defined as an Abbreviated Injury Scale (AIS) value of ≥3 in the thoracic area. Logistic regression analysis was used to evaluate the contribution of severe chest trauma to crude and adjusted ORs for mortality and to analyze the risk factors associated with mortality. Overall, 3821 patients (39%) presented severe chest trauma. The sample’s characteristics were as follows: a mean age of 49.88 (19.21) years, male (77.6%), blunt trauma (93.9%), a mean ISS of 19.9 (11.6). Crude and adjusted (for age and ISS) ORs for mortality in severe chest trauma were 0.78 (0.68–0.89) and 0.43 (0.37–0.50) (p < 0.001), respectively. In-hospital mortality in the severe chest trauma patients without significant traumatic brain injury (TBI) was 5.63% and was 25.71% with associated significant TBI (p < 0.001). Age, the severity of injury (NISS and AIS-head), hemodynamic instability, prehospital intubation, acute kidney injury, and multiorgan failure were risk factors associated with mortality. The contribution of severe chest injury to the mortality of trauma patients admitted to the ICU was very low. Risk factors associated with mortality were identified.
Cognitive Impairment in People with Epilepsy
Authors: Novak Ajda , Vizjak Karmen , Rakusa Martin
Published: January 2022

People with epilepsy frequently have cognitive impairment. The majority of cognitive problems is influenced by a variety of interlinked factors, including the early onset of epilepsy and the frequency, intensity and duration of seizures, along with the anti-epileptic drug treatment. With a systematic review, we investigate significant factors about the cognitive impairment in epilepsy. Most cognitive problems in adult people with epilepsy include memory, attention and executive function deficits. However, which cognitive area is mainly affected highly depends on the location of epileptic activity. Moreover, modifications in signalling pathways and neuronal networks have an essential role in both the pathophysiology of epilepsy and in the mechanism responsible for cognitive impairment. Additionally, studies have shown that the use of polytherapy in the treatment of epilepsy with anti-epileptic drugs (AEDs) heightens the risk for cognitive impairment. It can be challenging to distinguish the contribution of each factor, because they are often closely intertwined.
Newborn Hearing Screening Benefits Children, but Global Disparities Persist
Authors: Neumann Katrin , Mathmann Philipp , Chadha Shelly , Euler Harald A. , White Karl R.
Published: January 2022

There is substantial evidence that newborn hearing screening (NHS) reduces the negative sequelae of permanent childhood hearing loss (PCHL) if performed in programs that aim to screen all newborns in a region or nation (often referred to as Universal Newborn Hearing Screening or UNHS). The World Health Organization (WHO) has called in two resolutions for the implementation of such programs and for the collection of large-scale data. To assess the global status of NHS programs we surveyed individuals potentially involved with newborn and infant hearing screening (NIHS) in 196 countries/territories (in the following text referred to as countries). Replies were returned from 158 countries. The results indicated that 38% of the world’s newborns and infants had no or minimal hearing screening and 33% screened at least 85% of the babies (hereafter referred to as UNHS). Hearing screening programs varied considerably in quality, data acquisition, and accessibility of services for children with PCHL. In this article, we summarize the main results of the survey in the context of several recent WHO publications, particularly the World Report on Hearing, which defined advances in the implementation of NHS programs in the Member States as one of three key indicators of worldwide progress in ear and hearing care (EHC).
Correction: Rogowska et al. Changes in Stress, Coping Styles, and Life Satisfaction between the First and Second Waves of the COVID-19 Pandemic: A Longitudinal Cross-Lagged Study in a Sample of University Students. J. Clin. Med. 2021, 10, 4025
Authors: Rogowska Aleksandra Maria , Kuśnierz Cezary , Ochnik Dominika
Published: January 2022

The authors wish to make the following corrections to this paper [...]
The 2020 “Padua Criteria” for Diagnosis and Phenotype Characterization of Arrhythmogenic Cardiomyopathy in Clinical Practice
Authors: Graziano Francesca , Zorzi Alessandro , Cipriani Alberto , De Lazzari Manuel , Bauce Barbara , Rigato Ilaria , Brunetti Giulia , Pilichou Kalliopi , Basso Cristina , Perazzolo Marra Martina , Corrado Domenico
Published: January 2022

Arrhythmogenic Cardiomyopathy (ACM) is a heredo-familial cardiac disease characterized by fibro-fatty myocardial replacement and increased risk of sudden cardiac death. The diagnosis of ACM can be challenging due to the lack of a single gold-standard test: for this reason, it is required to satisfy a combination of multiple criteria from different categories including ventricular morpho-functional abnormalities, repolarization and depolarization ECG changes, ventricular arrhythmias, tissue characterization findings and positive family history/molecular genetics. The first diagnostic criteria were published by an International Task Force (ITF) of experts in 1994 and revised in 2010 with the aim to increase sensitivity for early diagnosis. Limitations of the 2010 ITF criteria include the absence of specific criteria for left ventricle (LV) involvement and the limited role of cardiac magnetic resonance (CMR) as the use of the late gadolinium enhancement technique for tissue characterization was not considered. In 2020, new diagnostic criteria (“the Padua criteria”) were proposed. The traditional organization in six categories of major/minor criteria was maintained. The criteria for identifying the right ventricular involvement were modified and a specific set of criteria for identifying LV involvement was created. Depending on the combination of criteria for right and LV involvement, a diagnosis of classic (right dominant) ACM, biventricular ACM or left-dominant ACM is then made. The article reviews the rationale of the Padua criteria, summarizes the main modifications compared to the previous 2010 ITF criteria and provides three examples of the application of the Padua criteria in clinical practice.
Modified Target Angle as a Predictor of Success in Strabismus Management after Orbital Fracture
Authors: Hsu Chih-Kang , Hsieh Meng-Wei , Chang Hsu-Chieh , Chen Yi-Hao , Chien Ke-Hung
Published: January 2022

Surgery for strabismus secondary to orbital fracture reconstruction surgery has had low success rates and high reoperation rates due to its incomitant nature and complex underlying mechanisms. There has been no consensus as to which of the various methods for improving the surgical results are best. We proposed a modified target angle criteria that combined the regular target angle and a favorable Hess area ratio percentage (HAR%) threshold to evaluate surgical results within the first postoperative week and conducted a retrospective chart review. According to the criteria of the modified target angle at the first postoperative week, a total of 63 patients were divided into two groups: Group 1, patients who fulfilled the criteria (49 patients); and Group 2, those who did not (14 patients). Sex, type of fracture, and the use of porous polyethylene sheets and titanium mesh during reconstruction surgery were significantly different between the groups. Group 1 showed a significantly higher percentage of patients who met the criteria of HAR% > 65% at the first week and >85% (i.e., a successful outcome) at the 6-month visit (p < 0.01). Additionally, Group 1 had a higher HAR% at the first postoperative week (p < 0.01). In conclusion, the patients meeting the criteria of the modified target angle at the first postoperative week had a favorable outcome at the 6-month visit in both ocular alignment and ocular movement.
Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis
Authors: Androulakis Emmanuel , Sohrabi Catrin , Briasoulis Alexandros , Bakogiannis Constantinos , Saberwal Bunny , Siasos Gerasimos , Tousoulis Dimitris , Ahsan Syed , Papageorgiou Nikolaos
Published: January 2022

Background: Catheter ablation (CA) for atrial fibrillation (AF) has been proposed as a means of improving outcomes among patients with heart failure and reduced ejection fraction (HFrEF) who are otherwise receiving appropriate treatment. Unlike HFrEF, treatment options are more limited in patients with preserved ejection fraction (HFpEF) and the data pertaining to the management of AF in these patients are controversial. The aim of this systematic review and meta-analysis was to investigate the effects of CA on outcomes of patients with AF and HFpEF, such as functional status, post-procedural complications, hospitalization, morbidity and mortality, based on data from observational studies. Methods: We systematically searched the electronic databases MEDLINE, PUBMED, EMBASE and the Cochrane Library for Central Register of Clinical Trials until May 2020. Results: Overall, the pooling of our data showed that sinus rhythm was achieved long-term in 58.0% (95% CI 0.44–0.71). Long-term AF recurrence was noticed in 22.3% of patients. Admission for HF occurred in 6.2% (95% CI 0.04–0.09) whilst all-cause mortality was identified in 6.3% (95% CI 0.02–0.13). Conclusion: This meta-analysis is the first to focus on determining the benefits of a rhythm control strategy for patients with AF and HFpEF using CA, suggesting it may be worthwhile to investigate the effects of a CA rhythm control strategy as the default treatment of AF in HFpEF patients in randomized trials.