bluuebunny/crossref_metadata_2025 huggingface dataset:
Test-Retest Reliability and Minimum Difference Values of a Novel and Portable Upright Row Strength Assessment in Probation Officers
Authors: Buoncristiani Nicholas A. , Mota Jacob A. , Gerstner Gena R. , Giuliani-Dewig Hayden K. , Ryan Eric D.
Published: January 2023

Upper body (UB) strength is important for occupational tasks and injury prevention in law enforcement officers (LEOs). Portable, reliable, and cost-effective assessments are needed to examine UB strength among LEOs in field settings. The purpose of this study was to examine the test-retest reliability and minimum difference (MD) values of a novel and portable isometric upright row assessment in probation officers. Thirty certified probation officers (18 women; age = 38.9 ± 9.0 years, body mass = 98.8 ± 27.1 kg, stature = 171.4 ± 14.0 cm) volunteered for this investigation. Testing occurred on-site across two sessions (2–5 days apart). Participants stood upon an aluminum plate with a chain attached to a handle and dynamometer. They grasped the handle with a pronated grip, two cm below the umbilicus, and performed three isometric maximal voluntary contractions. Intraclass correlation coefficient (ICC2,1), standard error of the measurement (SEM), and MD values were calculated. Results indicated no significant systematic error (p = 0.080) across sessions. The ICC2,1, SEM, and MD values for UB strength were 0.984, 27.20 N (4.1% of the mean), and 75.38 N (11.3% of the mean), respectively. These data suggest this isometric upright row assessment is a reliable, portable, and cost-effective measure of UB strength to assess and monitor LEOs in field settings.
Serologic Status of Borrelia burgdorferi sensu lato in Patients with Cardiovascular Changes
Authors: Pietruszka Katarzyna , Reagan Farbod , Stążka Janusz , Kozioł Małgorzata M.
Published: January 2023

Cardiovascular diseases, particularly coronary heart disease (CHD) caused by atherosclerosis, have the highest worldwide incidence and mortality rate of any type of disease. Aside from risk factors associated with lifestyle and comorbidities, infectious agents such as Borrelia burgdorferi sensu lato spirochetes, which cause Lyme disease, may also play a role in the development of cardiovascular disease. A growing number of scientific papers have mentioned Lyme carditis. The aim of this study was to find the level of anti-Borrelia IgG antibodies in the blood serum of patients with advanced coronary heart disease. Materials and methods: The study group included 70 patients undergoing coronary artery bypass grafting (CABG) and off-pump coronary artery bypass (OPCAB) surgery aged 50 to 82 (average 68.26). The ELISA test was used to detect anti-Borrelia/IgG antibodies in the blood serum. Serological testing revealed seropositivity in 34.29% of patients and ‘borderline results’ in 17.14% of patients. We found a link between antibody levels and tick bites but not with other risk factors for the development of CHD. Conclusions: These findings support the idea that, as one of many factors, the contact with spirochetal antigens may indicate a potential positive correlation with the formation of cardiovascular changes. More research, not only at the diagnostic level but also at the advanced research level, is needed.
The Importance of the Outdoor Environment for the Recovery of Psychiatric Patients: A Scoping Review
Authors: Hjort Mikkel , Mau Martin , Høj Michaela , Roessler Kirsten K.
Published: January 2023

(1) Background: Research has shown that patients with mental health diagnoses experience less anxiety and depressive symptoms and higher levels of ‘well-being’ when they spend time in natural environments as part of their treatment. It has been suggested that there is a relationship between the outdoor settings and the recovery of psychiatric patients. Recovery describes an individual process, which can vary from person to person. (2) Methods: This scoping review examined the relationship between the physical environment and the recovery of psychiatric patients. Systematic searches in three online databases, namely Medline, Embase, and PsycINFO, were performed using a selection of psychiatric, environmental, and recovery terms and included both quantitative and qualitative studies. In general, ‘well-being’ serves as an overarching indicator when it comes to research on how outdoor settings can affect mental health. Well-being was expressed in terms of mood, social relations, and autonomy. (3) Results: A total of 8138 records were screened, 85 studies were included for full-text reading, and five articles were included in the final analysis. The review showed in general that outdoor settings, more specifically gardening, contact with nature, and a safe environment can be related to the well-being of patients on psychiatric wards. (4) Conclusions: The five reviews allow us to conclude that outdoor settings can be seen as a comprehensive resource for mental health.
Green Management and Sustainable Performance of Small- and Medium-Sized Hospitality Businesses: Moderating the Role of an Employee’s Pro-Environmental Behaviour
Authors: Elshaer Ibrahim A. , Azazz Alaa M. S. , Fayyad Sameh
Published: January 2023

As green management practices (GMPs) matter not only for improving the organizations’ tribble line performance (environmental, economic, and social) but also can sustain a competitive advantage. Since the tourism and hospitality industry is subject to environmental expectations from visitors, governments, and the community, it is vital to understand what motivates GMPs to overcome environmental obstacles and satisfy those demands. However, the current literature fails to comprehensively justify how small- and medium-sized businesses (SMEs) tackle green management difficulties when implementing their plans, even though these SMEs could be a leading contributor to environmental concerns. Although many scholars assert that employees’ pro-environmental behaviours are decisive in boosting efforts of green management to improve corporate sustainable performance, only limited studies probed the importance of employees’ pro-environmental behaviours in SMEs in developing countries. To fill this research gap, the data was gathered from 304 small- and medium-sized hotels and travel agency middle managers using a self-administered survey approach. The collected data was analysed using the Smart PLS-structural equation modelling technique. The PLS-SEM results demonstrated that GMPs can improve environmental, economic, and social performance and these relationships can be strengthened through the moderating effects of employees’ pro-environmental behaviour. The study findings revealed that small- and medium-sized hospitality businesses should focus on creating a culture of environmental stewardship and actively involve employees in green initiatives to enhance sustainable performance. The study is important as it helps to understand the role of employee pro-environmental behaviour in green management and sustainable performance in small- and medium-sized hospitality businesses and can help the industry to adopt more sustainable practices. Several theoretical and practical implications were discussed and opportunities for further research were elaborated.
Ca2+-Dependent Effects of the Selenium-Sorafenib Nanocomplex on Glioblastoma Cells and Astrocytes of the Cerebral Cortex: Anticancer Agent and Cytoprotector
Authors: Varlamova Elena G. , Khabatova Venera V. , Gudkov Sergey V. , Turovsky Egor A.
Published: January 2023

Despite the fact that sorafenib is recommended for the treatment of oncological diseases of the liver, kidneys, and thyroid gland, and recently it has been used for combination therapy of brain cancer of various genesis, there are still significant problems for its widespread and effective use. Among these problems, the presence of the blood–brain barrier of the brain and the need to use high doses of sorafenib, the existence of mechanisms for the redistribution of sorafenib and its release in the brain tissue, as well as the high resistance of gliomas and glioblastomas to therapy should be considered the main ones. Therefore, there is a need to create new methods for delivering sorafenib to brain tumors, enhancing the therapeutic potential of sorafenib and reducing the cytotoxic effects of active compounds on the healthy environment of tumors, and ideally, increasing the survival of healthy cells during therapy. Using vitality tests, fluorescence microscopy, and molecular biology methods, we showed that the selenium-sorafenib (SeSo) nanocomplex, at relatively low concentrations, is able to bypass the mechanisms of glioblastoma cell chemoresistance and to induce apoptosis through Ca2+-dependent induction of endoplasmic reticulum stress, changes in the expression of selenoproteins and selenium-containing proteins, as well as key kinases-regulators of oncogenicity and cell death. Selenium nanoparticles (SeNPs) also have a high anticancer efficacy in glioblastomas, but are less selective, since SeSo in cortical astrocytes causes a more pronounced activation of the cytoprotective pathways.
Functional Characterization of Potato UBC13-UEV1s Genes Required for Ubiquitin Lys63 Chain to Polyubiquitination
Authors: Liu Weigang , Tang Xun , Fu Xue , Zhang Huanhuan , Zhu Cunlan , Zhang Ning , Si Huaijun
Published: January 2023

Ubiquitin-conjugating enzymes (E2s/UBC) are components of the ubiquitin proteasome system (UPS), and the ubiquitin-conjugating enzyme variant (UEV) is one of E2s (ubiquitin-conjugating enzymes, UBC) subfamily. The UEVs and UBC13 play an auxiliary role in mediating Lys63-linked polyUb chain assembly, which is correlated with target protein non-proteolytic functions, such as DNA repair or response to stress. However, the collaborative mechanism of StUBC13 (homologue of AtUBC13) and StUEVs (the UEVs in potato) involved in potato are not fully understood understood. Here, we identified two StUBC13 and seven StUEVs from potato genome. We analyzed protein motif and conserved domain, gene structure, phylogenetic features, cis-acting elements of StUBC13 and StUEVs. Subsequently, we screened StUBC13 partners protein and verified interaction between StUBC13 and StUEVs using yeast two-hybrid, split luciferase complementation (SLC) and bimolecular fluorescence complementation (BiFC) approach. The expression profile and qRT-PCR analysis suggested that StUBC13 and StUEVs gene exhibited a tissue-specific expression and were induced by different stress. Overall, this investigative study provides a comprehensive reference and view for further functional research on StUBC13 and StUEV1s in potato.
Cell Immunotherapy against Melanoma: Clinical Trials Review
Authors: Filin Ivan Y. , Mayasin Yuri P. , Kharisova Chulpan B. , Gorodilova Anna V. , Kitaeva Kristina V. , Chulpanova Daria S. , Solovyeva Valeriya V. , Rizvanov Albert A.
Published: January 2023

Melanoma is one of the most aggressive and therapy-resistant types of cancer, the incidence rate of which grows every year. However, conventional methods of chemo- and radiotherapy do not allow for completely removing neoplasm, resulting in local, regional, and distant relapses. In this case, adjuvant therapy can be used to reduce the risk of recurrence. One of the types of maintenance cancer therapy is cell-based immunotherapy, in which immune cells, such as T-cells, NKT-cells, B cells, NK cells, macrophages, and dendritic cells are used to recognize and mobilize the immune system to kill cancer cells. These cells can be isolated from the patient’s peripheral blood or biopsy material and genetically modified, cultured ex vivo, following infusion back into the patient for powerful induction of an anti-tumor immune response. In this review, the advantages and problems of the most relevant methods of cell-based therapy and ongoing clinical trials of adjuvant therapy of melanoma are discussed.
Organic–Inorganic Hybrid Pigments Based on Bentonite: Strategies to Stabilize the Quinoidal Base Form of Anthocyanin
Authors: Cunha Robson V. , Morais Alan I. S. , Trigueiro Pollyana , de Souza João Sammy N. , Damacena Dihêgo H. L. , Brandão-Lima Luciano C. , Bezerra Roosevelt D. S. , Fonseca Maria Gardennia , Silva-Filho Edson C. , Osajima Josy A.
Published: January 2023

Anthocyanins are one of the natural pigments that humanity has employed the most and can substitute synthetic food dyes, which are considered toxic. They are responsible for most purple, blue, and red pigment nuances in tubers, fruits, and flowers. However, they have some limitations in light, pH, oxygen, and temperature conditions. Combining biomolecules and inorganic materials such as clay minerals can help to reverse these limitations. The present work aims to produce materials obtained using cetyltrimethylammonium bromide in bentonite clay for incorporation and photostabilization of anthocyanin dye. Characterizations showed that the organic molecules were intercalated between the clay mineral layers, and the dye was successfully incorporated at a different pH. Visible light-driven photostability tests were performed with 200 h of irradiation, confirming that the organic–inorganic matrices were efficient enough to stabilize the quinoidal base form of anthocyanin. The pigment prepared at pH 10 was three-fold more stable than pH 4, showing that the increase in the synthesis pH promotes more stable colors, probably due to the stronger intermolecular interaction obtained under these conditions. Therefore, organobentonite hybrids allow to stabilize the fragile color coming from the quinoidal base form of anthocyanin dyes.
Lymphatic Dissemination in Prostate Cancer: Features of the Transcriptomic Profile and Prognostic Models
Authors: Pudova Elena A. , Kobelyatskaya Anastasiya A. , Katunina Irina V. , Snezhkina Anastasiya V. , Fedorova Maria S. , Pavlov Vladislav S. , Bakhtogarimov Ildar R. , Lantsova Margarita S. , Kokin Sergey P. , Nyushko Kirill M. , Alekseev Boris Ya. , Kalinin Dmitry V. , Melnikova Nataliya V. , Dmitriev Alexey A. , Krasnov George S. , Kudryavtseva Anna V.
Published: January 2023

Radical prostatectomy is the gold standard treatment for prostate cancer (PCa); however, it does not always completely cure PCa, and patients often experience a recurrence of the disease. In addition, the clinical and pathological parameters used to assess the prognosis and choose further tactics for treating a patient are insufficiently informative and need to be supplemented with new markers. In this study, we performed RNA-Seq of PCa tissue samples, aimed at identifying potential prognostic markers at the level of gene expression and miRNAs associated with one of the key signs of cancer aggressiveness—lymphatic dissemination. The relative expression of candidate markers was validated by quantitative PCR, including an independent sample of patients based on archival material. Statistically significant results, derived from an independent set of samples, were confirmed for miR-148a-3p and miR-615-3p, as well as for the CST2, OCLN, and PCAT4 genes. Considering the obtained validation data, we also analyzed the predictive value of models based on various combinations of identified markers using algorithms based on machine learning. The highest predictive potential was shown for the “CST2 + OCLN + pT” model (AUC = 0.863) based on the CatBoost Classifier algorithm.
Detection of High Level of Co-Infection and the Emergence of Novel SARS CoV-2 Delta-Omicron and Omicron-Omicron Recombinants in the Epidemiological Surveillance of Andalusia
Authors: Perez-Florido Javier , Casimiro-Soriguer Carlos S. , Ortuño Francisco , Fernandez-Rueda Jose L. , Aguado Andrea , Lara María , Riazzo Cristina , Rodriguez-Iglesias Manuel A. , Camacho-Martinez Pedro , Merino-Diaz Laura , Pupo-Ledo Inmaculada , de Salazar Adolfo , Viñuela Laura , Fuentes Ana , Chueca Natalia ,   The Andalusian COVID-19 Sequencing Initiative, García Federico , Dopazo Joaquín , Lepe Jose A.
Published: January 2023

Recombination is an evolutionary strategy to quickly acquire new viral properties inherited from the parental lineages. The systematic survey of the SARS-CoV-2 genome sequences of the Andalusian genomic surveillance strategy has allowed the detection of an unexpectedly high number of co-infections, which constitute the ideal scenario for the emergence of new recombinants. Whole genome sequence of SARS-CoV-2 has been carried out as part of the genomic surveillance programme. Sample sources included the main hospitals in the Andalusia region. In addition to the increase of co-infections and known recombinants, three novel SARS-CoV-2 delta-omicron and omicron-omicron recombinant variants with two break points have been detected. Our observations document an epidemiological scenario in which co-infection and recombination are detected more frequently. Finally, we describe a family case in which co-infection is followed by the detection of a recombinant made from the two co-infecting variants. This increased number of recombinants raises the risk of emergence of recombinant variants with increased transmissibility and pathogenicity.
Hypoxia and Intestinal Inflammation: Common Molecular Mechanisms and Signaling Pathways
Authors: Dvornikova Kristina A. , Platonova Olga N. , Bystrova Elena Y.
Published: January 2023

The gastrointestinal tract (GI) has a unique oxygenation profile. It should be noted that the state of hypoxia can be characteristic of both normal and pathological conditions. Hypoxia-inducible factors (HIF) play a key role in mediating the response to hypoxia, and they are tightly regulated by a group of enzymes called HIF prolyl hydroxylases (PHD). In this review, we discuss the involvement of inflammation hypoxia and signaling pathways in the pathogenesis of inflammatory bowel disease (IBD) and elaborate in detail on the role of HIF in multiple immune reactions during intestinal inflammation. We emphasize the critical influence of tissue microenvironment and highlight the existence of overlapping functions and immune responses mediated by the same molecular mechanisms. Finally, we also provide an update on the development of corresponding therapeutic approaches that would be useful for treatment or prophylaxis of inflammatory bowel disease.
Light Drives and Temperature Modulates: Variation of Phenolic Compounds Profile in Relation to Photosynthesis in Spring Barley
Authors: Vrábl Daniel , Nezval Jakub , Pech Radomír , Volná Adriana , Mašková Petra , Pleva Jan , Kuzniciusová Nikola , Provazová Michaela , Štroch Michal , Špunda Vladimír
Published: January 2023

Accumulation and metabolic profile of phenolic compounds (PheCs; serving as UV-screening pigments and antioxidants) as well as carbon fixation rate (An) and plant growth are sensitive to irradiance and temperature. Since these factors are naturally co-acting in the environment, it is worthy to study the combined effects of these environmental factors to assess their possible physiological consequences. We investigated how low and high irradiance in combination with different temperatures modify the metabolic profile of PheCs and expression of genes involved in the antioxidative enzyme and PheCs biosynthesis, in relation to photosynthetic activity and availability of non-structural carbohydrates (NSC) in spring barley seedlings. High irradiance positively affected An, NSC, PheCs content, and antioxidant activity (AOX). High temperature led to decreased An, NSC, and increased dark respiration, whilst low temperature was accompanied by reduction of UV-A shielding but increase of PheCs content and AOX. Besides that, irradiance and temperature caused changes in the metabolic profile of PheCs, particularly alteration in homoorientin/isovitexin derivatives ratio, possibly related to demands on AOX-based protection. Moreover, we also observed changes in the ratio of sinapoyl-/feruloyl- acylated flavonoids, the function of which is not yet known. The data also strongly suggested that the NSC content may support the PheCs production.
Gene Expression Profile of Uterine Leiomyoma from Women Exposed to Different Air Pollution Levels in Metropolitan Cities of Sao Paulo, Brazil
Authors: dos Anjos Laura Gonzalez , de Almeida Bruna Cristine , Baracat Edmund Chada , Al-Hendy Ayman , Yang Qiwei , Carvalho Katia Candido
Published: January 2023

Leiomyomas (LMs) are the most frequent uterine benign tumors, representing the leading cause of hysterectomy indications worldwide. They are highly associated with women’s reproductive complications, and endocrine disruptors may influence their etiology. In this sense, air pollution represents a relevant hormonal disruptor that acts on key signaling pathways, resulting in tumor development and infertility. Our goal was to evaluate submucosal LM samples from patients living in the metropolitan and Sao Paulo city regions, focusing on genes involved in tumor development and infertility features. Twenty-four patients were selected based on their region of residence and clinical information availability. Several genes were differentially expressed between women living in metropolitan areas and Sao Paulo city. Significant associations were observed between BCL-2, DVL1, FGFR3, and WNT5b downregulation and contraceptive use in the samples from women living in Sao Paulo city. ESR1 and HHAT downregulation was associated with ethnicity. WNT5b and GREM were associated with LM treatment and related pathologies, respectively. In the samples from women living in other cities of the metropolitan region, abortion occurrence was associated with BMP4 upregulation. Although further studies may be necessary, our results showed that air pollution exposure influences the expression of genes related to LM development and female reproductive features.
Synthesis of Nitrogen and Phosphorus/Sulfur Co-Doped Carbon Xerogels for the Efficient Electrocatalytic Reduction of p-Nitrophenol
Authors: Wang Chaolong , Zhu Dengxia , Bi Huiting , Zhang Zheng , Zhu Junjiang
Published: January 2023

Carbon xerogels co-doped with nitrogen (N) and phosphorus (P) or sulfur (S) were synthesized and employed as catalysts for the electrocatalytic reduction of p-nitrophenol (p-NP). The materials were prepared by first synthesizing N-doped carbon xerogels (NDCX) via the pyrolysis of organic gels, and then introducing P or S atoms to the NDCX by a vapor deposition method. The materials were characterized by various measurements including X-ray diffraction, N2 physisorption, Transmission electron microscopy, Fourier Infrared spectrometer, and X-ray photoelectron spectra, which showed that N atoms were successfully doped to the carbon xerogels, and the co-doping of P or S atoms affected the existing status of N atoms. Cyclic voltammetry (CV) scanning manifested that the N and P co-doped materials, i.e., P-NDCX-1.0, was the most suitable catalyst for the reaction, showing an overpotential of −0.569 V (vs. Ag/AgCl) and a peak slop of 695.90 μA/V. The material was also stable in the reaction and only a 14 mV shift in the reduction peak overpotential was observed after running for 100 cycles.
MoaE Is Involved in Response to Oxidative Stress in Deinococcus radiodurans
Authors: Cai Jianling , Zhang Maoxu , Chen Zijing , Zhao Ye , Xu Hong , Tian Bing , Wang Liangyan , Hua Yuejin
Published: January 2023

Molybdenum ions are covalently bound to molybdenum pterin (MPT) to produce molybdenum cofactor (Moco), a compound essential for the catalytic activity of molybdenum enzymes, which is involved in a variety of biological functions. MoaE is the large subunit of MPT synthase and plays a key role in Moco synthesis. Here, we investigated the function of MoaE in Deinococcus radiodurans (DrMoaE) in vitro and in vivo, demonstrating that the protein contributed to the extreme resistance of D. radiodurans. The crystal structure of DrMoaE was determined by 1.9 Å resolution. DrMoaE was shown to be a dimer and the dimerization disappeared after Arg110 had been mutated. The deletion of drmoaE resulted in sensitivity to DNA damage stress and a slower growth rate in D. radiodurans. The increase in drmoaE transcript levels the and accumulation of intracellular reactive oxygen species levels under oxidative stress suggested that it was involved in the antioxidant process in D. radiodurans. In addition, treatment with the base analog 6-hydroxyaminopurine decreased survival and increased intracellular mutation rates in drmoaE deletion mutant strains. Our results reveal that MoaE plays a role in response to external stress mainly through oxidative stress resistance mechanisms in D. radiodurans.
CRISPR/Cas9-Targeted Disruption of Two Highly Homologous Arabidopsis thaliana DSS1 Genes with Roles in Development and the Oxidative Stress Response
Authors: Nikolić Ivana , Samardžić Jelena , Stevanović Strahinja , Miljuš-Đukić Jovanka , Milisavljević Mira , Timotijević Gordana
Published: January 2023

Global climate change has a detrimental effect on plant growth and health, causing serious losses in agriculture. Investigation of the molecular mechanisms of plant responses to various environmental pressures and the generation of plants tolerant to abiotic stress are imperative to modern plant science. In this paper, we focus on the application of the well-established technology CRISPR/Cas9 genome editing to better understand the functioning of the intrinsically disordered protein DSS1 in plant response to oxidative stress. The Arabidopsis genome contains two highly homologous DSS1 genes, AtDSS1(I) and AtDSS1(V). This study was designed to identify the functional differences between AtDSS1s, focusing on their potential roles in oxidative stress. We generated single dss1(I) and dss1(V) mutant lines of both Arabidopsis DSS1 genes using CRISPR/Cas9 technology. The homozygous mutant lines with large indels (dss1(I)del25 and dss1(V)ins18) were phenotypically characterized during plant development and their sensitivity to oxidative stress was analyzed. The characterization of mutant lines revealed differences in root and stem lengths, and rosette area size. Plants with a disrupted AtDSS1(V) gene exhibited lower survival rates and increased levels of oxidized proteins in comparison to WT plants exposed to oxidative stress induced by hydrogen peroxide. In this work, the dss1 double mutant was not obtained due to embryonic lethality. These results suggest that the DSS1(V) protein could be an important molecular component in plant abiotic stress response.
N-Doped Carbon/CeO2 Composite as a Biomimetic Catalyst for Antibacterial Application
Authors: Wang Nan , Zhai Xiaofan , Guan Fang , Zhang Ruiyong , Hou Baorong , Duan Jizhou
Published: January 2023

Exploring new and high efficiency mimic enzymes is a vital and novel strategy for antibacterial application. Haloperoxidase-like enzymes have attracted wide attention thanks to their amazing catalytic property for hypohalous acid generation from hydrogen peroxide and halides. However, few materials have displayed halogenating catalytic performance until now. Herein, we synthesized N-doped C/CeO2 (N-C/CeO2) composite materials by a combination of the liquid and solid-state method. N-C/CeO2 can possess haloperoxidase-like catalytic activity by catalyzing the bromination of organic signaling compounds (phenol red) with H2O2 at a wide range of temperatures (20 °C to 55 °C), with a solution color changing from yellow to blue. Meanwhile, it exhibits high catalytic stability/recyclability in the catalytic reaction. The synthesized N-C/CeO2 composite can effectively catalyze the oxidation of Br− with H2O2 to produce HBrO without the presence of phenol red. The produced HBrO can resist typical marine bacteria like Pseudomonas aeruginosa. This study provides an efficient biomimetic haloperoxidase and a novel sustainable method for antibacterial application.
Foggia Prostate Cancer Risk Calculator 2.0: A Novel Risk Calculator including MRI and Bladder Outlet Obstruction Parameters to Reduce Unnecessary Biopsies
Authors: Falagario Ugo Giovanni , Busetto Gian Maria , Recchia Marco , Tocci Edoardo , Selvaggio Oscar , Ninivaggi Antonella , Milillo Paola , Macarini Luca , Sanguedolce Francesca , Mancini Vito , Annese Pasquale , Bettocchi Carlo , Carrieri Giuseppe , Cormio Luigi
Published: January 2023

Risk calculator (RC) combining PSA with other clinical information can help to better select patients at risk of prostate cancer (PCa) for prostate biopsy. The present study aimed to develop a new Pca RC, including MRI and bladder outlet obstruction parameters (BOOP). The ability of these parameters in predicting PCa and clinically significant PCa (csPCa: ISUP GG ≥ 2) was assessed by binary logistic regression. A total of 728 patients were included from two institutions. Of these, 395 (54.3%) had negative biopsies and 161 (22.11%) and 172 (23.6%) had a diagnosis of ISUP GG1 PCa and csPCa. The two RC ultimately included age, PSA, DRE, prostate volume (pVol), post-voided residual urinary volume (PVR), and PIRADS score. Regarding BOOP, higher prostate volumes (csPCa: OR 0.98, CI 0.97,0.99) and PVR ≥ 50 mL (csPCa: OR 0.27, CI 0.15, 0.47) were protective factors for the diagnosis of any PCa and csPCa. AUCs after internal validation were 0.78 (0.75, 0.82) and 0.82 (0.79, 0.86), respectively. Finally, decision curves analysis demonstrated higher benefit compared to the first-generation calculator and MRI alone. These novel RC based on MRI and BOOP may help to better select patient for prostate biopsy after prostate MRI.
Phage Engineering for Targeted Multidrug-Resistant Escherichia coli
Authors: Song Jiaoyang , Liu Zhengjie , Zhang Qing , Liu Yuqing , Chen Yibao
Published: January 2023

The lytic bacteriophages have potential application value in the treatment of bacterial infections. However, the narrow host spectrum of these phages limits their range of clinical application. Here, we demonstrate the use of scarless Cas9-assisted recombination (no-SCAR) gene-editing technology to regulate phage–host range. We used phage PHB20 as the scaffold to create agents targeting different multidrug-resistant Escherichia coli by replacing its phage tail fiber gene (ORF40). The engineered phages were polyvalent and capable of infecting both the original host bacteria and new targets. Phage-tail fiber genes can be amplified by PCR to construct a recombinant phage PHB20 library that can deal with multidrug-resistant bacteria in the future. Our results provide a better understanding of phage–host interactions, and we describe new anti-bacterial editing methods.
SAV-Pred: A Freely Available Web Application for the Prediction of Pathogenic Amino Acid Substitutions for Monogenic Hereditary Diseases Studied in Newborn Screening
Authors: Zadorozhny Anton D. , Rudik Anastasia V. , Filimonov Dmitry A. , Lagunin Alexey A.
Published: January 2023

Next Generation Sequencing (NGS) technologies are rapidly entering clinical practice. A promising area for their use lies in the field of newborn screening. The mass screening of newborns using NGS technology leads to the discovery of a large number of new missense variants that need to be assessed for association with the development of hereditary diseases. Currently, the primary analysis and identification of pathogenic variations is carried out using bioinformatic tools. Although extensive efforts have been made in the computational approach to variant interpretation, there is currently no generally accepted pathogenicity predictor. In this study, we used the sequence–structure–property relationships (SSPR) approach, based on the representation of protein fragments by molecular structural formula. The approach predicts the pathogenic effect of single amino acid substitutions in proteins related with twenty-five monogenic heritable diseases from the Uniform Screening Panel for Major Conditions recommended by the Advisory Committee on Hereditary Disorders in Newborns and Children. In order to create SSPR models of classification, we modified a piece of cheminformatics software, MultiPASS, that was originally developed for the prediction of activity spectra for drug-like substances. The created SSPR models were compared with traditional bioinformatic tools (SIFT 4G, Polyphen-2 HDIV, MutationAssessor, PROVEAN and FATHMM). The average AUC of our approach was 0.804 ± 0.040. Better quality scores were achieved for 15 from 25 proteins with a significantly higher accuracy for some proteins (IVD, HADHB, HBB). The best SSPR models of classification are freely available in the online resource SAV-Pred (Single Amino acid Variants Predictor).
Role of Echocardiography in Diabetic Cardiomyopathy: From Mechanisms to Clinical Practice
Authors: Urlic Hrvoje , Kumric Marko , Vrdoljak Josip , Martinovic Dinko , Dujic Goran , Vilovic Marino , Ticinovic Kurir Tina , Bozic Josko
Published: January 2023

It has been well established that diabetes mellitus (DM) is considered as a core risk factor for the development of cardiovascular diseases. However, what is less appreciated is the fact that DM may affect cardiac function irrespective of cardiac pathologies to which it contributes, such as coronary artery disease and hypertension. Although echocardiography provides accurate and reproducible diagnostic and prognostic data in patients with DM, its use in these patients is still underappreciated, resulting in progression of DM-related heart failure in many patients. Hence, in the present review, we aimed to discuss the role of echocardiography in the contemporary management of diabetic cardiomyopathy (DCM), as well as the role of emerging echocardiographic techniques, which may contribute to earlier diagnosis and more appropriate management of this complication of DM. In order to improve outcomes, focus must be placed on early diagnosis of this condition using a combination of echocardiography and emerging biomarkers, but perhaps the more important thing is to change perspective when it comes to the clinical importance of DCM.
The Performance of GALAD Score for Diagnosing Hepatocellular Carcinoma in Patients with Chronic Liver Diseases: A Systematic Review and Meta-Analysis
Authors: Guan Ming-Cheng , Zhang Shi-Yu , Ding Qian , Li Na , Fu Ting-Ting , Zhang Gui-Xia , He Qian-Qian , Shen Feng , Yang Tian , Zhu Hong
Published: January 2023

Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its diagnostic ability has been validated in different populations with a wide variation. Therefore, we conducted a meta-analysis to investigate its overall diagnostic performance in differentiating HCC in chronic liver diseases. Methods Eligible studies were searched in the Web of Science, PubMed, Scopus, Ovid, Cochrane Library, and Embase databases by 29 May 2022. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals (CI) were estimated. Results Fifteen original studies (comprising 19,021 patients) were included. For detecting any-stage HCC, GALAD score yielded an excellent ability, with pooled sensitivity, specificity, and AUC of 0.82 (95%CI: 0.78–0.85), 0.89 (95%CI: 0.85–0.91), and 0.92 (95%CI: 0.89–0.94), respectively. Notably, further analyses demonstrated a good diagnostic accuracy of GALAD score for identifying Barcelona Clinic Liver Cancer staging (BCLC) 0/A HCC, with a moderate sensitivity (0.73 (95%CI: 0.66–0.79)) and a high specificity (0.87 (95%CI: 0.81–0.91)); by contrast, only 38% of early-stage patients can be identified by alpha-fetoprotein, with an AUC value of 0.70 (95%CI: 0.66–0.74). Following subgroup analyses based on different HCC etiologies, higher sensitivities and AUC values were observed in subgroups with hepatitis C or non-viral liver diseases. For detecting BCLC 0/A HCC in the cirrhotic population, GALAD score had a pooled sensitivity, specificity, and AUC of 0.78 (95%CI: 0.66–0.87), 0.80 (95%CI: 0.72–0.87), and 0.86 (95%CI: 0.83–0.89). Conclusions We highlighted the superior diagnostic accuracy of GALAD score for detecting any-stage HCC with a high sensitivity and specificity, especially for early-stage HCC, with a relatively stable diagnostic performance. The addition of GALAD score into ultrasound surveillance may identify more HCC patients. Our findings imply the robust power of the GALAD score as a HCC screening or diagnostic tool, and it should be further validated by more studies with high quality.
Donor and Donation Images (DDI)—A Scoping Review of What We Know and What We Don’t
Authors: Laskowski Nora M. , Brandt Gerrit , Tigges-Limmer Katharina , Halbeisen Georg , Paslakis Georgios
Published: January 2023

Organ transplantation is associated with significant physical and psychological burden for the recipients. Qualitative reports indicate that organ recipients develop donor and donation images (DDI)—conceptions of the donor and/or the organ. A deeper understanding of DDI is needed in the care of transplant recipients. To present the current state of knowledge, we searched for and identified DDI-related publications in PubMed and Scopus. Inclusion criteria were (1) studies addressing transplant recipients, and (2) English or German language. Twenty-one studies of individuals with transplanted hearts, lungs, or kidneys were included in this scoping review. Prevalence for DDI ranged from 6% to 52.3%. DDI occurs both before and after transplantation and includes ideas about the donor as well as whether and how the recipient’s personality may be altered by the transplanted organ. Some transplant recipients did indeed report personality changes following transplantation due to the adoption of assumed donor characteristics. One study showed a positive association between the presence of DDI and anxiety scores and one described a coping effect. DDI is understudied and should be systematically assessed to improve care for the vulnerable group of individuals undergoing organ transplantation. Current research gaps and future directions are discussed.
Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex—Current Views on Their Pathogenesis and Management
Authors: Gao Chao , Zabielska Bernadeta , Jiao Fuyong , Mei Daoqi , Wang Xiaona , Kotulska Katarzyna , Jozwiak Sergiusz
Published: January 2023

Introduction, Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder caused by mutations inactivating TSC1 or TSC2 genes and characterized by the presence of tumors involving many organs, including the brain, heart, kidneys, and skin. Subependymal giant cell astrocytoma (SEGA) is a slow-growing brain tumor almost exclusively associated with TSC. State of the Art: Despite the fact that SEGAs are benign, they require well-considered decisions regarding the timing and modality of pharmacological or surgical treatment. In TSC children and adolescents, SEGA is the major cause of mortality and morbidity. Clinical Implications: Until recently, surgical resection has been the standard therapy for SEGAs but the discovery of the role of the mTOR pathway and the introduction of mTOR inhibitors to clinical practice changed the therapeutic landscape of these tumors. In the current paper, we discuss the pros and cons of mTOR inhibitors and surgical approaches in SEGA treatment. Future Directions: In 2021, the International Tuberous Sclerosis Complex Consensus Group proposed a new integrative strategy for SEGA management. In the following review, we discuss the proposed recommendations and report the results of the literature search for the latest treatment directions.
Evolution of Rheumatoid-Arthritis-Associated Interstitial Lung Disease in Patients Treated with JAK Inhibitors: A Retrospective Exploratory Study
Authors: Venerito Vincenzo , Manfredi Andreina , Carletto Antonio , Gentileschi Stefano , Atzeni Fabiola , Guiducci Serena , Lavista Marlea , La Corte Laura , Pedrollo Elisa , Scardapane Arnaldo , Tomassini Caterina , Frediani Bruno , Salvarani Carlo , Iannone Florenzo , Sebastiani Marco
Published: January 2023

Background: The aim of this multicenter retrospective study was to investigate the effectiveness and safety of the available JAK-inhibitors (JAKi) in patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD). Methods: We retrospectively analyzed patients with classified RA and RA-ILD undergoing JAKi in 6 Italian tertiary centers from April 2018 to June 2022. We included patients with at least 6 months of active therapy and one high-resolution chest tomography (HRCT) carried out within 3 months of the start of JAKi treatment. The HRCT was then compared to the most recent one carried out within 3 months before the last available follow-up appointment. We also kept track of the pulmonary function tests. Results: We included 43 patients with RA-ILD and 23 males (53.48%) with a median age (interquartile range, IQR) of 68.87 (61.46–75.78) treated with JAKi. The median follow-up was 19.1 months (11.03–34.43). The forced vital capacity remained stable in 22/28 (78.57%) patients, improved in 3/28 (10.71%) and worsened in 3/28 (10.71%). The diffusing capacity of lung for carbon monoxide showed a similar trend, remaining stable in 18/25 (72%) patients, improving in 2/25 (8%) and worsening in 5/25 (20%). The HRCT remained stable in 37/43 (86.05) cases, worsened in 4/43 (9.30%) and improved in the last 2 (4.65%). Discussion: This study suggests that JAKi therapy might be a safe therapeutic option for patients with RA-ILD in a short-term follow-up.
Cardiovascular Reasons for Access to a Tertiary Oncological Emergency Service: The CARILLON Study
Authors: Imberti Jacopo F. , Maisano Anna , Rampini Francesca , Minnocci Melania , Bertuglia Filippo , Mantovani Marta , Cherubini Benedetta , Mei Davide A. , Ferrara Leonardo , Bonini Niccolò , Valenti Anna Chiara , Vitolo Marco , Longo Giuseppe , Boriani Giuseppe
Published: January 2023

Background: The prevalence of acute cardiovascular diseases (CVDs) in cancer patients is steadily increasing and represents a significant reason for admission to the emergency department (ED). Methods: We conducted a prospective observational study, enrolling consecutive patients with cancer presenting to a tertiary oncological ED and consequently admitted to the oncology ward. Two groups of patients were identified based on main symptoms that lead to ED presentation: symptoms potentially related to CVD vs. symptoms potentially not related to CVD. The aims of the study were to describe the prevalence of symptoms potentially related to CVD in this specific setting and to evaluate the prevalence of definite CV diagnoses at discharge. Secondary endpoints were new intercurrent in-hospital CV events occurrence, length of stay in the oncology ward, and mid-term mortality for all-cause. Results: A total of 469 patients (51.8% female, median age 68.0 [59.1–76.3]) were enrolled. One hundred and eighty-six out of 469 (39.7%) presented to the ED with symptoms potentially related to CVD. Baseline characteristics were substantially similar between the two study groups. A discharge diagnosis of CVD was confirmed in 24/186 (12.9%) patients presenting with symptoms potentially related to CVD and in no patients presenting without symptoms potentially related to CVD (p < 0.01). During a median follow-up of 3.4 (1.2–6.5) months, 204 (43.5%) patients died (incidence rate of 10.1 per 100 person/months). No differences were found between study groups in terms of all-cause mortality (hazard ratio [HR]: 0.85, 95% confidence interval [CI] 0.64–1.12), new in-hospital CV events (HR: 1.03, 95% CI 0.77–1.37), and length of stay (p = 0.57). Conclusions: In a contemporary cohort of cancer patients presenting to a tertiary oncological ED and admitted to an oncology ward, symptoms potentially related to CVD were present in around 40% of patients, but only a minority were actually diagnosed with an acute CVD.
Time Trends in Clinical Characteristics and Hospital Outcomes of Hospitalizations for Lung Transplantation in COPD Patients in Spain from 2016 to 2020—Impact of the COVID-19 Pandemic
Authors: De Miguel-Diez Javier , Jimenez-Garcia Rodrigo , Hernández-Barrera Valentin , Carabantes-Alarcon David , Zamorano-Leon Jose , Cuadrado-Corrales Natividad , Omaña-Palanco Ricardo , González-Barcala Francisco , Lopez-de-Andres Ana
Published: January 2023

(1) Background: To examine the clinical characteristics and hospital outcomes of hospitalization for lung transplantation in COPD patients in Spain from 2016 to 2020; and to assess if the COVID-19 pandemic has affected the number or the outcomes of lung transplantations in these patients. (2) Methods: We used the Spanish National Hospital Discharge Database to select subjects who had a code for COPD (ICD-10: J44) and had undergone a lung transplantation (ICD-10 codes OBYxxxx). (3) Results: During the study period, 704 lung transplants were performed among COPD patients (single 31.68%, bilateral 68.32%). The absolute number of transplants increased with raising rates of 8%, 14% and 19% annually from 2016 to 2019. However, a marked decrease of −18% was observed from 2019 to year 2020. Overall, 47.44% of the patients suffered at least one complication, being the most frequent lung transplant rejection (24.15%), followed by lung transplant infection (13.35%). The median length of hospital stay (LOHS) was 33 days and the in-hospital-mortality (IHM) was 9.94%. Variables associated with increased risk of mortality were a Comorbidity Charlson Index ≥ 1 (OR 1.82; 95%CI 1.08–3.05) and suffering any complication of the lung transplantation (OR 2.14; 95%CI 1.27–3.6). COPD patients in 2020 had a CCI ≥ 1 in a lower proportion than 2019 patients (29.37 vs. 38.51%; p = 0.015) and less frequently suffered any complications after the lung transplantation (41.26 vs. 54.6%; p = 0.013), no changes in the LOHS or the IHM were detected from 2019 to 2020. (4) Conclusions: Our study showed a constant increase in the number of lung transplantations from 2016 to 2019 in COPD patients, with a drop from 2019 to 2020, probably related to the COVID-19 pandemic. However, no changes in LOHS or IHM were detected over time.
Prophylaxis of Invasive Fungal Infection in Neonates: A Narrative Review for Practical Purposes
Authors: Ferrando Giulia , Castagnola Elio
Published: January 2023

Candida albicans is the most frequent cause of invasive fungal disease in preterm and/or low birth weight neonates, followed by Candida parapsilosis, whilst infections from other species are rare. Considering the severity of the disease, associated with poor clinical signs and diagnostic difficulties, primary prophylaxis becomes relevant. This paper summarizes the pathogenesis and clinical presentation of invasive candidiasis in neonates, focusing on prophylaxis. For late onset invasive disease, e.g., those occurring after the 3rd (or 7th according to some definitions) day of life possible approaches are the use of fluconazole, recommended in case of weight <1000 g or <1500 g if the local incidence of invasive candidiasis is higher than 2%, or the use of nystatin (for patients < 1500 g). Micafungin must be used in case of colonization by Candida auris, or in centers with a high prevalence of this pathogen. Concurrently, correct management of the central venous catheter and isolation procedures, with special regard to patients colonized by resistant strains, are fundamental. Other approaches such as reduced use of H2 blockers and broad-spectrum antibiotics (e.g., 3rd generation cephalosporins or carbapenems) and promotion of breast feeding proved useful. Reduction of early-onset infections (those occurring in the first 3 days of life) can also be obtained by treating maternal vulvo–vaginal candidiasis, which can represent a fastidious problem during pregnancy. In this case, topic azoles (the only recommendable treatment) can represent a kind of “prophylaxis” of early neonatal candidiasis. However, it must always be remembered that prophylaxis reduces the risk of invasive candidiasis but can not completely eliminate its occurrence, with the parallel risk of selecting for antifungal-resistant strains. Clinicians must maintain a high level of suspicion to start an appropriate therapy and strict epidemiological surveillance to identify the occurrence of clusters and the appearance of strains resistant to prophylaxis.