bluuebunny/crossref_metadata_2025 huggingface dataset:
A Qualitative Exploration of Sources of Help for Mental Illness in Arabic-, Mandarin-, and Swahili-Speaking Communities in Sydney, Australia
Authors: Krstanoska-Blazeska Klimentina , Renzaho Andre , Blignault Ilse , Li Bingqin , Reavley Nicola , Slewa-Younan Shameran
Published: May 2023

Despite being disproportionately affected by poor mental health, culturally and linguistically diverse (CaLD) individuals seek help from mental health services at lower rates than others in the Australian population. The preferred sources of help for mental illness amongst CaLD individuals remain poorly understood. The aim of this study was to explore sources of help in Arabic-, Mandarin-, and Swahili-speaking communities in Sydney, Australia. Eight focus-group discussions (n = 51) and twenty-six key informant interviews were undertaken online using Zoom. Two major themes were identified: informal sources of help and formal sources of help. Under the informal sources of help theme, three sub-themes were identified: social, religious, and self-help sources. All three communities strongly recognised the role of social sources of help, with more nuanced roles held by religion and self-help activities. Formal sources of help were described by all communities, although to a lesser extent than informal sources. Our findings suggest that interventions to support help-seeking for all three communities should involve building the capacity of informal sources of help, utilising culturally appropriate environments, and the collaboration between informal and formal sources of help. We also discuss differences between the three communities and offer service providers insights into unique issues that require attention when working with these groups.
A Developmental Psychopathology Perspective on Political Violence and Youth Adjustment
Authors: Wentz Bethany , Miller-Graff Laura E. , Merrilees Christine E. , Cummings E. Mark
Published: May 2023

According to the United Nations (2021), [...]
Who Gets the Flu? Individualized Validation of Influenza-like Illness in Urban Spaces
Authors: Zhong Shiran , Ma Fenglong , Gao Jing , Bian Ling
Published: May 2023

Urban dwellers are exposed to communicable diseases, such as influenza, in various urban spaces. Current disease models are able to predict health outcomes at the individual scale but are mostly validated at coarse scales due to the lack of fine-scaled ground truth data. Further, a large number of transmission-driving factors have been considered in these models. Because of the lack of individual-scaled validations, the effectiveness of factors at their intended scale is not substantiated. These gaps significantly undermine the efficacy of the models in assessing the vulnerability of individuals, communities, and urban society. The objectives of this study are twofold. First, we aim to model and, most importantly, validate influenza-like illness (ILI) symptoms at the individual scale based on four sets of transmission-driving factors pertinent to home–work space, service space, ambient environment, and demographics. The effort is supported by an ensemble approach. For the second objective, we investigate the effectiveness of the factor sets through an impact analysis. The validation accuracy reaches 73.2–95.1%. The validation substantiates the effectiveness of factors pertinent to urban spaces and unveils the underlying mechanism that connects urban spaces and population health. With more fine-scaled health data becoming available, the findings of this study may see increasing value in informing policies that improve population health and urban livability.
Physical Function and Association with Cognitive Function in Patients in a Post-COVID-19 Clinic—A Cross-Sectional Study
Authors: Gunnarsson Durita Viderø , Miskowiak Kamilla Woznica , Pedersen Johanna Kølle , Hansen Henrik , Podlekareva Daria , Johnsen Stine , Dall Christian Have
Published: May 2023

Patients with long-term health sequelae of COVID-19 (post-COVID-19 condition) experience both physical and cognitive manifestations. However, there is still uncertainty about the prevalence of physical impairment in these patients and whether there is a link between physical and cognitive function. The aim was to assess the prevalence of physical impairment and investigate the association with cognition in patients assessed in a post-COVID-19 clinic. In this cross-sectional study, patients referred to an outpatient clinic ≥ 3 months after acute infection underwent screening of their physical and cognitive function as part of a comprehensive multidisciplinary assessment. Physical function was assessed with the 6-Minute Walk Test, the 30 s Sit-to-Stand Test and by measuring handgrip strength. Cognitive function was assessed with the Screen for Cognitive Impairment in Psychiatry and the Trail Making Test-Part B. Physical impairment was tested by comparing the patients’ performance to normative and expected values. Association with cognition was investigated using correlation analyses and the possible explanatory variables regarding physical function were assessed using regression analyses. In total, we included 292 patients, the mean age was 52 (±15) years, 56% were women and 50% had been hospitalised during an acute COVID-19 infection. The prevalence of physical impairment ranged from 23% in functional exercise capacity to 59% in lower extremity muscle strength and function. There was no greater risk of physical impairment in previously hospitalised compared with the non-hospitalised patients. There was a weak to moderate association between physical and cognitive function. The cognitive test scores had statistically significant prediction value for all three outcomes of physical function. In conclusion, physical impairments were prevalent amongst patients assessed for post-COVID-19 condition regardless of their hospitalisation status and these were associated with more cognitive dysfunction.
Targeted Therapies in Small Cell Lung Cancer: From Old Failures to Novel Therapeutic Strategies
Authors: Cani Massimiliano , Napoli Valerio Maria , Garbo Edoardo , Ferrari Giorgia , Del Rio Benedetta , Novello Silvia , Passiglia Francesco
Published: May 2023

The clinical management of small cell lung cancer (SCLC) treatment remains a major challenge for thoracic oncologists, with very few therapeutic advances significantly impacting patients’ survival. The recent introduction of immunotherapy in the clinical setting produced a marginal benefit for a limited subset of metastatic patients, while the therapeutic scenario for relapsing extended-disease small cell lung cancers (ED-SCLCs) remains almost deserted. Recent efforts clarified the molecular features of this disease, leading to the identification of key signalling pathways which may serve as potential targets for clinical use. Despite the large number of molecules tested and the numerous therapeutic failures, some targeted therapies have recently shown interesting preliminary results. In this review, we describe the main molecular pathways involved in SCLC development/progression and provide an updated summary of the targeted therapies currently under investigation in SCLC patients.
Impact of Intratracheal Administration of Polyethylene Glycol-Coated Silver Nanoparticles on the Heart of Normotensive and Hypertensive Mice
Authors: Nemmar Abderrahim , Al-Salam Suhail , Greish Yaser E. , Beegam Sumaya , Zaaba Nur E. , Ali Badreldin H.
Published: May 2023

Silver nanoparticles are widely used in various industrial and biomedical applications; however, little is known about their potential cardiotoxicity after pulmonary exposure, particularly in hypertensive subjects. We assessed the cardiotoxicity of polyethylene glycol (PEG)-coated AgNPs in hypertensive (HT) mice. Saline (control) or PEG–AgNPs (0.5 mg/kg) were intratracheally (i.t.) instilled four times (on days 7, 14, 21, and 28 post-angiotensin II or vehicle [saline] infusion). On day 29, various cardiovascular parameters were evaluated. Systolic blood pressure and heart rate were higher in PEG–AgNPs-treated HT mice than in saline-treated HT or PEG–AgNPs-treated normotensive mice. The heart histology of PEG–AgNPs-treated HT mice had comparatively larger cardiomyocyte damage with fibrosis and inflammatory cells when compared with saline-treated HT mice. Similarly, the relative heart weight and the activities of lactate dehydrogenase and creatine kinase-MB and the concentration of brain natriuretic peptide concentration were significantly augmented in heart homogenates of HT mice treated with PEG–AgNPs compared with HT mice treated with saline or normotensive animals exposed to PEG–AgNPs. Similarly, the concentrations of endothelin-1, P-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in heart homogenates were significantly higher than in the other two groups when HT mice were exposed to PEG–AgNPs. Markers of inflammation and oxidative and nitrosative stress were significantly elevated in heart homogenates of HT mice given PEG–AgNPs compared with HT mice treated with saline or normotensive animals exposed to PEG–AgNPs. The hearts of HT mice exposed to PEG–AgNPs had significantly increased DNA damage than those of HT mice treated with saline or normotensive mice treated with AgNPs. In conclusion, the cardiac injury caused by PEG–AgNPs was aggravated in hypertensive mice. The cardiotoxicity of PEG–AgNPs in HT mice highlights the importance of an in-depth assessment of their toxicity before using them in clinical settings, particularly in patients with pre-existing cardiovascular diseases.
Investigating the Properties and Characterization of a Hybrid 3D Printed Antimicrobial Composite Material Using FFF Process: Innovative and Swift
Authors: Ahmed Waleed , Al-Marzouqi Ali H. , Nazir Muhammad Hamza , Rizvi Tahir A. , Zaneldin Essam , Khan Mushtaq , Aziz Muthanna
Published: May 2023

Novel strategies and materials have gained the attention of researchers due to the current pandemic, the global market high competition, and the resistance of pathogens against conventional materials. There is a dire need to develop cost-effective, environmentally friendly, and biodegradable materials to fight against bacteria using novel approaches and composites. Fused filament fabrication (FFF), also known as fused deposition modeling (FDM), is the most effective and novel fabrication method to develop these composites due to its various advantages. Compared to metallic particles alone, composites of different metallic particles have shown excellent antimicrobial properties against common Gram-positive and Gram-negative bacteria. This study investigates the antimicrobial properties of two sets of hybrid composite materials, i.e., Cu-PLA-SS and Cu-PLA-Al, are made using copper-enriched polylactide composite, one-time printed side by-side with stainless steel/PLA composite, and second-time with aluminum/PLA composite respectively. These materials have 90 wt.% of copper, 85 wt.% of SS 17-4, 65 wt.% of Al with a density of 4.7 g/cc, 3.0 g/cc, and 1.54 g/cc, respectively, and were fabricated side by side using the fused filament fabrication (FFF) printing technique. The prepared materials were tested against Gram-positive and Gram-negative bacteria such as Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), Salmonella Poona (S. Poona), and Enterococci during different time intervals (5 min, 10 min, 20 min, 1 h, 8 h, and 24 h). The results revealed that both samples showed excellent antimicrobial efficiency, and 99% reduction was observed after 10 min. Hence, three-dimensional (3D) printed polymeric composites enriched with metallic particles can be utilized for biomedical, food packaging, and tissue engineering applications. These composite materials can also provide sustainable solutions in public places and hospitals where the chances of touching surfaces are higher.
Unraveling the Role of Adiponectin Receptors in Obesity-Related Breast Cancer
Authors: Naimo Giuseppina Daniela , Paolì Alessandro , Giordano Francesca , Forestiero Martina , Panno Maria Luisa , Andò Sebastiano , Mauro Loredana
Published: May 2023

Obesity has a noteworthy role in breast tumor initiation and progression. Among the mechanisms proposed, the most validated is the development of chronic low-grade inflammation, supported by immune cell infiltration along with dysfunction in adipose tissue biology, characterized by an imbalance in adipocytokines secretion and alteration of their receptors within the tumor microenvironment. Many of these receptors belong to the seven-transmembrane receptor family, which are involved in physiological features, such as immune responses and metabolism, as well as in the development and progression of several malignancies, including breast cancer. These receptors are classified as canonical (G protein-coupled receptors, GPCRs) and atypical receptors, which fail to interact and activate G proteins. Among the atypical receptors, adiponectin receptors (AdipoRs) mediate the effect of adiponectin, the most abundant adipocytes-derived hormone, on breast cancer cell proliferation, whose serum levels are reduced in obesity. The adiponectin/AdipoRs axis is becoming increasingly important regarding its role in breast tumorigenesis and as a therapeutic target for breast cancer treatment. The objectives of this review are as follows: to point out the structural and functional differences between GPCRs and AdipoRs, and to focus on the effect of AdipoRs activation in the development and progression of obesity-dependent breast cancer.
State-of-the-Art Molecular Plant Sciences in Brazil
Authors: dos Reis Pedro Augusto Braga , Magalhaes Jurandir Vieira , Miller Robert Neil Gerard , Fontes Elizabeth Pacheco Batista
Published: May 2023

Brazil has a crucial role in global food security and biodiversity, boasting one of the largest agricultural areas and two globally vital biomes, the Amazon and the Atlantic Forest [...]
Formation of a Purple Product upon the Reaction of ABTS Radicals with Proteins
Authors: Kut Kacper , Stefaniuk Ireneusz , Bartosz Grzegorz , Sadowska-Bartosz Izabela
Published: May 2023

The reaction of the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) free radical (ABTS●) with proteins (bovine serum albumin, blood plasma, egg white, erythrocyte membranes, and Bacto Peptone) leads not only to a reduction of ABTS● but also to the appearance of a purple color (absorption maximum at 550–560 nm). The aim of this study was to characterize the formation and explain the nature of the product responsible for the appearance of this color. The purple color co-precipitated with protein, and was diminished by reducing agents. A similar color was generated by tyrosine upon reaction with ABTS●. The most feasible explanation for the color formation is the addiction of ABTS● to proteins’ tyrosine residues. The product formation was decreased by nitration of the bovine serum albumin (BSA) tyrosine residues. The formation of the purple product of tyrosine was optimal at pH 6.5. A decrease in pH induced a bathochromic shift of the spectra of the product. The product was not a free radical, as demonstrated by electrom paramagnetic resonance (EPR) spectroscopy. Another byproduct of the reaction of ABTS● with tyrosine and proteins was dityrosine. These byproducts can contribute to the non-stoichiometry of the antioxidant assays with ABTS●. The formation of the purple ABTS adduct may be a useful index of radical addition reactions of protein tyrosine residues.
Transcriptomic and Proteomic Landscape of Sugarcane Response to Biotic and Abiotic Stressors
Authors: Li Ao-Mei , Liao Fen , Wang Miao , Chen Zhong-Liang , Qin Cui-Xian , Huang Ruo-Qi , Verma Krishan K. , Li Yang-Rui , Que You-Xiong , Pan You-Qiang , Huang Dong-Liang
Published: May 2023

Sugarcane, a C4 plant, provides most of the world’s sugar, and a substantial amount of renewable bioenergy, due to its unique sugar-accumulating and feedstock properties. Brazil, India, China, and Thailand are the four largest sugarcane producers worldwide, and the crop has the potential to be grown in arid and semi-arid regions if its stress tolerance can be improved. Modern sugarcane cultivars which exhibit a greater extent of polyploidy and agronomically important traits, such as high sugar concentration, biomass production, and stress tolerance, are regulated by complex mechanisms. Molecular techniques have revolutionized our understanding of the interactions between genes, proteins, and metabolites, and have aided in the identification of the key regulators of diverse traits. This review discusses various molecular techniques for dissecting the mechanisms underlying the sugarcane response to biotic and abiotic stresses. The comprehensive characterization of sugarcane’s response to various stresses will provide targets and resources for sugarcane crop improvement.
Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the Hippocampus
Authors: Madokoro Yuta , Kato Daisuke , Tsuda Yo , Arakawa Itsumi , Suzuki Kengo , Sato Toyohiro , Mizuno Masayuki , Uchida Yuto , Ojika Kosei , Matsukawa Noriyuki
Published: May 2023

The cholinergic efferent network from the medial septal nucleus to the hippocampus is crucial for learning and memory. This study aimed to clarify whether hippocampal cholinergic neurostimulating peptide (HCNP) has a rescue function in the cholinergic dysfunction of HCNP precursor protein (HCNP-pp) conditional knockout (cKO). Chemically synthesized HCNP or a vehicle were continuously administered into the cerebral ventricle of HCNP-pp cKO mice and littermate floxed (control) mice for two weeks via osmotic pumps. We immunohistochemically measured the cholinergic axon volume in the stratum oriens and functionally evaluated the local field potential in the CA1. Furthermore, choline acetyltransferase (ChAT) and nerve growth factor (NGF) receptor (TrkA and p75NTR) abundances were quantified in wild-type (WT) mice administered HCNP or the vehicle. As a result, HCNP administration morphologically increased the cholinergic axonal volume and electrophysiological theta power in HCNP-pp cKO and control mice. Following the administration of HCNP to WT mice, TrkA and p75NTR levels also decreased significantly. These data suggest that extrinsic HCNP may compensate for the reduced cholinergic axonal volume and theta power in HCNP-pp cKO mice. HCNP may function complementarily to NGF in the cholinergic network in vivo. HCNP may represent a therapeutic candidate for neurological diseases with cholinergic dysfunction, e.g., Alzheimer’s disease and Lewy body dementia.
αvβ3 Integrin as a Link between the Development of Fibrosis and Thyroid Hormones in Systemic Sclerosis
Authors: Kohon Maia Yamila , Zaaroor Levy Mor , Hornik-Lurie Tzipi , Shalom Avshalom , Berl Ariel , Drucker Liat , Levy Yair , Tartakover Matalon Shelly
Published: May 2023

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Key players mediating fibrosis are myofibroblasts (MF) that, following transforming growth factor β (TGFβ) exposure, produce a collagen-rich extracellular matrix (ECM) that induces myofibroblast differentiation. Myofibroblasts express αvβ3 integrin (a membrane receptor for thyroid hormones) and miRNA-21 that promotes deiodinase-type-3 expression (D3), causing the degradation of triiodothyronine (T3) that attenuates fibrosis. We hypothesized that αvβ3 affects the fibrotic processes through its thyroid hormones (THs) binding site. To test this, dermal fibroblasts (DF) were cultured with/without TGFβ and removed with a base, leaving only normal/fibrotic ECMs in wells. Then, DF were cultured on the ECMs with/without tetrac (αvβ3 ligand, T4 antagonist), and evaluated for pro-fibrotic characteristics, αvβ3, miRNA-21, and D3 levels. Blood free-T3 (fT3), miRNA-21 levels, and the modified Rodnan skin score (MRSS) were evaluated in SSc patients. We found that the “fibrotic-ECM” significantly increased the pro-fibrotic characteristics of DF and the levels of miRNA-21, D3, and αvβ3, compared to the “normal-ECM.” Tetrac significantly inhibited the effects of the “fibrotic-ECM” on the cells. In accordance with tetrac’s effect on D3/miRNA-21, a negative correlation was found between the patients’ fT3 to miRNA-21 levels, and to the development of pulmonary arterial hypertension (PAH). We conclude that occupying the THs binding site of αvβ3 may delay the development of fibrosis.
Effect of Secretion Efficiency of Mutant KRAS Neoantigen by Lactococcus lactis on the Immune Response of a Mucosal Vaccine Delivery Vehicle Targeting Colorectal Cancer
Authors: Alias Nur Aqlili Riana , Hoo Winfrey Pui Yee , Siak Pui Yan , Othman Siti Sarah , Mohammed Alitheen Noorjahan Banu , In Lionel Lian Aun , Abdul Rahim Raha , Song Adelene Ai-Lian
Published: May 2023

Colorectal cancer (CRC) is often caused by mutations in the KRAS oncogene, making KRAS neoantigens a promising vaccine candidate for immunotherapy. Secreting KRAS antigens using live Generally Recognized as Safe (GRAS) vaccine delivery hosts such as Lactococcus lactis is deemed to be an effective strategy in inducing specific desired responses. Recently, through the engineering of a novel signal peptide SPK1 from Pediococcus pentosaceus, an optimized secretion system was developed in the L. lactis NZ9000 host. In this study, the potential of the L. lactis NZ9000 as a vaccine delivery host for the production of two KRAS oncopeptides (mutant 68V-DT and wild-type KRAS) through the use of the signal peptide SPK1 and its mutated derivative (SPKM19) was investigated. The expression and secretion efficiency analyses of KRAS peptides from L. lactis were performed in vitro and in vivo in BALB/c mice. Contradictory to our previous study using the reporter staphylococcal nuclease (NUC), the yield of secreted KRAS antigens mediated by the target mutant signal peptide SPKM19 was significantly lower (by ~1.3-folds) compared to the wild-type SPK1. Consistently, a superior elevation of IgA response against KRAS aided by SPK1 rather than mutant SPKM19 was observed. Despite the lower specific IgA response for SPKM19, a positive IgA immune response from mice intestinal washes was successfully triggered following immunization. Size and secondary conformation of the mature proteins are suggested to be the contributing factors for these discrepancies. This study proves the potential of L. lactis NZ9000 as a host for oral vaccine delivery due to its ability to evoke the desired mucosal immune response in the gastrointestinal tract of mice.
Effect of the Temperature on the Process of Preferential Solvation of 1,4-Dioxane, 12-Crown-4, 15-Crown-5 and 18-Crown-6 Ethers in the Mixture of N-Methylformamide with Water: Composition of the Solvation Shell of the Cyclic Ethers
Authors: Jóźwiak Małgorzata , Trzmielak Monika A. , Wasiak Michał
Published: May 2023

The aim of the work was to analyze the preferential solvation process, and determine the composition of the solvation shell of cyclic ethers using the calorimetric method. The heat of solution of 1,4-dioxane, 12-crown-4, 15-crown-5 and 18-crown-6 ethers in the mixture of N-methylformamide with water was measured at four temperatures, 293.15 K, 298.15 K, 303.15 K, and 308.15 K, and the standard partial molar heat capacity of cyclic ethers has been discussed. 18-crown-6 (18C6) molecules can form complexes with NMF molecules through the hydrogen bonds between –CH3 group of NMF and the oxygen atoms of 18C6. Using the model of preferential solvation, the cyclic ethers were observed to be preferentially solvated by NMF molecules. It has been proved that the molar fraction of NMF in the solvation shell of cyclic ethers is higher than that in the mixed solvent. The exothermic, enthalpic effect of preferential solvation of cyclic ethers increases with increasing ring size and temperature. The increase in the negative effect of the structural properties of the mixed solvent with increase in the ring size in the process of preferential solvation of the cyclic ethers indicates an increasing disturbance of the mixed solvent structure, which is reflected in the influence of the energetic properties of the mixed solvent.
Expression Pattern of Sonic Hedgehog, Patched and Smoothened in Clear Cell Renal Carcinoma
Authors: Dunatov Huljev Ana , Kelam Nela , Benzon Benjamin , Šoljić Violeta , Filipović Natalija , Pešutić Pisac Valdi , Glavina Durdov Merica , Vukojević Katarina
Published: May 2023

Clear cell renal cell carcinoma (ccRCC) is the deadliest neoplasm of the urinary tract, and we are still far from completely understanding ccRCC development and treatment. The renal tissue paraffin blocks (20) of patients with ccRCC were collected at the University Hospital in Split from 2019 to 2020, and tissue sections were stained with patched (PTCH), anti-smoothened (SMO) and anti-Sonic Hedgehog (SHH) antibodies. SHH was highly expressed (31.9%) in grade 1 tumour, it being higher than all other grades and the control (p < 0.001–p < 0.0001). The trend of a linear decrease in the expression of SHH was observed with the progression of the tumour grade (p < 0.0001). PTCH expression was significantly lower in grades 1 and 2 in comparison to the control (p < 0.01) and grade 4 (p < 0.0001). A significant increase in the expression of SMO was found in grade 4 compared to all other grades (p < 0.0001) and the control (p < 0.001). The strong expression of SHH was observed in carcinoma cells of the G1 stage with a diffuse staining pattern (>50% of neoplastic cells). Stroma and/or inflammatory infiltrate display no staining and no expression of SHH in G1 and G2, while mild focal staining (10–50% of neoplastic cells) was observed in G3 and G4. Patients with high PTCH and low SMO expression had significant time survival differences (p = 0.0005 and p = 0.029, respectively). Therefore, high levels of PTCH and low levels of SMO expression are important markers of better survival rates in ccRCC patients.
Adipokine-Cytokine Profile in Patients with Unstable Atherosclerotic Plaques and Abdominal Obesity
Authors: Garbuzova (Striukova) Evgeniia V. , Shramko Victoriya S. , Kashtanova Elena V. , Polonskaya Yana V. , Stakhneva Ekaterina M. , Kurguzov Alexey V. , Murashov Ivan S. , Chernyavsky Alexander M. , Ragino Yuliya I.
Published: May 2023

The goal of the research was to study the levels of adipokines and their associations with unstable atherosclerotic plaques in patients with coronary atherosclerosis and abdominal obesity (AO). Methods: The study included 145 men aged 38–79 with atherosclerosis of the coronary arteries (CA) and stable angina pectoris II-III FC who were hospitalized for coronary bypass surgery (2011–2022). The final analysis included 116 patients. Notably, 70 men had stable plaques in the CA (of which 44.3% had AO), and 46 men had unstable plaques in the CA (of which 43.5% had AO). Adipocytokine levels were determined using multiplex analysis (Human Metabolic Hormone V3 panel). Results: In the subgroup of patients with unstable plaques, patients with AO had a GLP-1 level that was 1.5 times higher and a lipocalin-2 level that was 2.1 times lower, respectively. GLP-1 is direct, and lipocalin-2 is inversely associated with AO in patients with unstable plaques. Among patients with AO, the level of lipocalin-2 in patients with unstable plaques was 2.2 times lower than in patients with stable plaques in the CA. The level of lipocalin-2 was inversely associated with the presence of unstable atherosclerotic plaques in the CA. Conclusion: GLP-1 is directly associated with AO in patients with unstable atherosclerotic plaques. Lipocalin-2 is inversely associated with unstable atherosclerotic plaques in patients with AO.
Multi-Gene Next-Generation Sequencing Panel for Analysis of BRCA1/BRCA2 and Homologous Recombination Repair Genes Alterations Metastatic Castration-Resistant Prostate Cancer
Authors: Maloberti Thais , De Leo Antonio , Coluccelli Sara , Sanza Viviana , Gruppioni Elisa , Altimari Annalisa , Zagnoni Stefano , Giunchi Francesca , Vasuri Francesco , Fiorentino Michelangelo , Mollica Veronica , Ferrari Simona , Miccoli Sara , Visani Michela , Turchetti Daniela , Massari Francesco , Tallini Giovanni , de Biase Dario
Published: May 2023

Despite significant therapeutic advances, metastatic CRPC (mCRPC) remains a lethal disease. Mutations in homologous recombination repair (HRR) genes are frequent in mCRPC, and tumors harboring these mutations are known to be sensitive to PARP inhibitors. The aim of this study was to verify the technical effectiveness of this panel in the analysis of mCRPC, the frequency and type of mutations in the BRCA1/BRCA2 genes, as well as in the homologous recombination repair (HRR) genes. A total of 50 mCRPC cases were analyzed using a multi-gene next-generation sequencing panel evaluating a total of 1360 amplicons in 24 HRR genes. Of the 50 cases, 23 specimens (46.0%) had an mCRPC harboring a pathogenic variant or a variant of uncertain significance (VUS), whereas in 27 mCRPCs (54.0%), no mutations were detected (wild-type tumors). BRCA2 was the most commonly mutated gene (14.0% of samples), followed by ATM (12.0%), and BRCA1 (6.0%). In conclusion, we have set up an NGS multi-gene panel that is capable of analyzing BRCA1/BRCA2 and HRR alterations in mCRPC. Moreover, our clinical algorithm is currently being used in clinical practice for the management of patients with mCRPC.
Interrelationship between COVID-19 and Coagulopathy: Pathophysiological and Clinical Evidence
Authors: Ragnoli Beatrice , Da Re Beatrice , Galantino Alessandra , Kette Stefano , Salotti Andrea , Malerba Mario
Published: May 2023

Since the first description of COVID-19 infection, among clinical manifestations of the disease, including fever, dyspnea, cough, and fatigue, it was observed a high incidence of thromboembolic events potentially evolving towards acute respiratory distress syndrome (ARDS) and COVID-19-associated-coagulopathy (CAC). The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status of COVID-19 can be explained by the increase in coagulation levels of D-dimer, lymphocytes, fibrinogen, interleukin 6 (IL-6), and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction, and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.
Stearoyl-CoA Desaturase 1 as a Therapeutic Biomarker: Focusing on Cancer Stem Cells
Authors: Min Jin-Young , Kim Do-Hee
Published: May 2023

The dysregulation of lipid metabolism and alterations in the ratio of monounsaturated fatty acids (MUFAs) to saturated fatty acids (SFAs) have been implicated in cancer progression and stemness. Stearoyl-CoA desaturase 1 (SCD1), an enzyme involved in lipid desaturation, is crucial in regulating this ratio and has been identified as an important regulator of cancer cell survival and progression. SCD1 converts SFAs into MUFAs and is important for maintaining membrane fluidity, cellular signaling, and gene expression. Many malignancies, including cancer stem cells, have been reported to exhibit high expression of SCD1. Therefore, targeting SCD1 may provide a novel therapeutic strategy for cancer treatment. In addition, the involvement of SCD1 in cancer stem cells has been observed in various types of cancer. Some natural products have the potential to inhibit SCD1 expression/activity, thereby suppressing cancer cell survival and self-renewal activity.
Acute Myeloid Leukemia Causes Serious and Partially Irreversible Changes in Secretomes of Bone Marrow Multipotent Mesenchymal Stromal Cells
Authors: Sadovskaya Aleksandra , Petinati Nataliya , Drize Nina , Smirnov Igor , Pobeguts Olga , Arapidi Georgiy , Lagarkova Maria , Belyavsky Alexander , Vasilieva Anastasia , Aleshina Olga , Parovichnikova Elena
Published: May 2023

In patients with acute myeloid leukemia (AML), malignant cells modify the properties of multipotent mesenchymal stromal cells (MSCs), reducing their ability to maintain normal hematopoiesis. The aim of this work was to elucidate the role of MSCs in supporting leukemia cells and the restoration of normal hematopoiesis by analyzing ex vivo MSC secretomes at the onset of AML and in remission. The study included MSCs obtained from the bone marrow of 13 AML patients and 21 healthy donors. The analysis of proteins contained in the MSCs-conditioned medium demonstrated that secretomes of patient MSCs differed little between the onset of AML and remission; pronounced differences were observed between MSC secretomes of AML patients and healthy donors. The onset of AML was accompanied by a decrease in the secretion of proteins related to ossification, transport, and immune response. In remission, but not at the onset, secretion of proteins responsible for cell adhesion, immune response, and complement was reduced compared to donors. We conclude that AML causes crucial and, to a large extent, irreversible changes in the secretome of bone marrow MSCs ex vivo. In remission, functions of MSCs remain impaired despite the absence of tumor cells and the formation of benign hematopoietic cells.
A Theoretical Study of Organotin Binding in Aromatase
Authors: Cheng Shuming , Yang Jing
Published: May 2023

The widely used organotin compounds are notorious for their acute toxicity. Experiments revealed that organotin might cause reproductive toxicity by reversibly inhibiting animal aromatase functioning. However, the inhibition mechanism is obscure, especially at the molecular level. Compared to experimental methods, theoretical approaches via computational simulations can help to gain a microscopic view of the mechanism. Here, in an initial attempt to uncover the mechanism, we combined molecular docking and classical molecular dynamics to investigate the binding between organotins and aromatase. The energetics analysis indicated that the van der Waals interaction is the primary driving force of binding the organic tail of organotin and the aromatase center. The hydrogen bond linkage trajectory analysis revealed that water plays a significant role in linking the ligand–water–protein triangle network. As an initial step in studying the mechanism of organotin inhibiting aromatase, this work provides an in-depth understanding of the binding mechanism of organotin. Further, our study will help to develop effective and environmentally friendly methods to treat animals that have already been contaminated by organotin, as well as sustainable solutions for organotin degradation.
Tetragonal Nanosized Zirconia: Hydrothermal Synthesis and Its Performance as a Promising Ceramic Reinforcement
Authors: Liu Shikai , Wang Jialin , Chen Yingxin , Song Zhijian , Han Bibo , Wu Haocheng , Zhang Taihang , Liu Meng
Published: May 2023

In this study, we produced zirconia nanoparticles with a pure tetragonal phase, good dispersion, and an average particle size of approximately 7.3 nm using the modified hydrothermal method. Zirconium oxychloride (ZrOCl2-8H2O) was used as zirconium source, while propanetriol was used as an additive. The influence of propanetriol content, sonication time, hydrothermal temperature, and type of dispersant on the physical phase and dispersibility of zirconia nanoparticles was investigated. Monoclinic zirconia was found to completely transform into a tetragonal structure when the mass fraction of glycerol was increased to 5 wt%. With the increase in the mechanical stirring time under ultrasonic conditions, the size distribution range of the prepared particles became narrower and then wider, and the particle size became first smaller and then larger. Ultrasonic and mechanical stirring for 5 min had the best effect. When comparing the effects of different dispersants (PEG8000, PVP, and CTAB), it was found that the average particle size of zirconia nanoparticles prepared with 0.5 wt% PVP was the smallest. Furthermore, by adding different concentrations of pure tetragonal phase nanozirconia to 3Y-ZrO2 as reinforcement additives, the bending strength of the prepared ceramics increased first and then decreased with increasing addition amounts. When the amount of addition was 1 wt% and the ceramic was calcined at 1600 °C, the flexural strength of the ceramic increased significantly, which was about 1.6 times that of the unadded ceramic. The results are expected to provide a reference for the reinforcement of high-purity zirconia ceramics.
Predicting the Distribution of Sclerodermus sichuanensis (Hymenoptera: Bethylidae) under Climate Change in China
Authors: Gao Hui , Qian Qianqian , Liu Lijuan , Xu Danping
Published: May 2023

Sclerodermus sichuanensis is the natural enemy of the longicorn beetle due to its strong attack ability and high parasitic rate. Its good resistance and fecundity make it have significant biological control value. The Maxent model and ArcGIS software were used to simulate the current distribution of S. sichuanensis in China by combining the known distribution information and environmental variables and predict the suitable area of the 2050s (2041–2060) and 2090s (2081–2000) under three climate scenarios (SSP1-2.6, SSP2-4.5. and SSP5-8.5). The results showed that the Mean Diurnal Range (bio2), Min Temperature of the Coldest Month (bio6), Precipitation of the Warmest Quarter (bio18), and Max Temperature of the Warmest Month (bio5) were the key environmental variables affecting the distribution of S. sichuanensis. Southwest China and part of North China are the main concentrations of the current high-suitability areas of S. sichuanensis. The moderately suitable areas are concentrated in South China and Central China. Under the SSP5-8.5 scenario, the suitable area predicted in the 2050s will expand significantly to North China and Northwest China, with a total increase of 81,295 km2. This work provides an essential reference for future research on S. sichuanensis and the application of forestry pest control.
Evaluation of Long-Term Outcomes of Direct Acting Antiviral Agents in Chronic Kidney Disease Subjects: A Single Center Cohort Study
Authors: Czarnecka Paulina , Czarnecka Kinga , Tronina Olga , Bączkowska Teresa , Wyczałkowska-Tomasik Aleksandra , Durlik Magdalena , Czerwinska Katarzyna
Published: May 2023

Background: The chronic kidney disease (CKD) population, including kidney transplant recipients (KTRs) and subjects on renal replacement therapy, is particularly vulnerable to unfavorable outcomes from chronic hepatitis C (CHC). Currently, there are oral direct-acting antiviral agents (DAAs) available to eradicate the virus with favorable short-term outcomes; however, their long-term effects are lacking. The aim of the study is to assess the long-term efficacy and safety of DAA therapy in the CKD population. Methods: An observational, cohort single-center study was performed. Fifty-nine CHC subjects with CKD, treated with DAAs between 2016 and 2018, were enrolled in the study. Safety and efficacy profiles were assessed, including sustained virologic response (SVR), occult hepatitis C infection (OCI) incidence, and liver fibrosis. Results: SVR was achieved in 96% of cases (n = 57). OCI was diagnosed only in one subject following SVR. Significant liver stiffness regression was observed 4 years after SVR compared to baseline values (Mdn = 6.1 kPa, IQR = 3.75 kPa; 4.9 kPa, IQR = 2.9 kPa), p < 0.001. The most common adverse events were anemia, weakness, and urinary tract infection. Conclusion: DAAs provide a safe and effective cure for CHC in both CKD patients and KTRs with a favorable safety profile in the long-term follow-up.
Clinical Characteristics of Headache in Multiple Sclerosis Patients: A Cross-Sectional Study
Authors: Rościszewska-Żukowska Iwona , Galiniak Sabina , Bartosik-Psujek Halina
Published: May 2023

Primary headaches are known to be associated with multiple sclerosis (MS), but previous studies concerning this relationship are not conclusive. Nowadays, there are no studies assessing the prevalence of headaches in Polish MS patients. The aim of the study was to assess the prevalence and characterise headaches in MS patients treated with disease-modifying therapies (DMTs). In a cross-sectional study of 419 consecutive RRMS patients, primary headaches were diagnosed according to the International Classification of Headache Disorders (ICHD-3) criteria. Primary headaches were observed in 236 (56%) of RRMS patients, with a higher prevalence in women (ratio of 2:1). The most common was migraine 174 (41%) (migraine with aura 80 (45%), migraine without aura 53 (30%), and probable migraine without aura 41 (23%); less frequent was tension-type headache 62 (14%). Female sex was a risk factor for migraines but not for tension-type headaches (p = 0.002). Migraines mostly started before MS onset (p = 0.023). Migraine with aura was associated with older age, longer disease duration (p = 0.028), and lower SDMT (p = 0.002). Longer DMT time was associated with migraine (p = 0.047), particularly migraine with aura (p = 0.035). Typical for migraine with aura were headaches during clinical isolated syndrome (CIS) (p = 0.001) and relapses (p = 0.025). Age and type of CIS, oligoclonal band presence, family MS history, EDSS, 9HTP, T25FW, and type of DMT did not correlate with headache. Headaches are present in more than half of MS patients treated with DMTs; migraines occur almost three times more frequently than tension-type headaches. Migraines with aura headaches during CIS and relapses are typical. Migraine in MS patients had high severity and typical migraine characteristics. DMTs had no correlation with the presence or type of headache.
A Novel Approach to Staging and Detection of Colorectal Cancer in Early Stages
Authors: Zajkowska Monika , Mroczko Barbara
Published: May 2023

Colorectal cancer (CRC) is a significant problem affecting patients all over the world. Since it is the fourth most common cause of cancer-related deaths, many scientists aim to expand their knowledge on the detection in early stages and treatment of this disease. Chemokines, as protein parameters involved in many processes accompanying the development of cancer, constitute a group of potential biomarkers that could also be useful in the detection of CRC. For this purpose, our research team used the results of thirteen parameters (nine chemokines, one chemokine receptor and three comparative markers, i.e., CEA, CA19-9 and CRP) to calculate one hundred and fifty indexes. Moreover, for the first time, the relationship between these parameters during the ongoing cancer process and in comparison to a control group are presented. As a result of statistical analyses using patients’ clinical data and the obtained indexes, it was established that several of the indexes have a diagnostic utility that is much higher than the tumor marker that is currently the most commonly used (CEA) currently. Furthermore, two of the indexes (CXCL14/CEA and CXCL16/CEA) showed not only extremely high usefulness in the detection of CRC in its early stages, but also the ability to determine whether the stage is low (stage I and II) or high (stage III and IV).
The Practice of Fast-Track Liver Transplant Anesthesia
Authors: Aniskevich Stephen , Scott Courtney L. , Ladlie Beth L.
Published: May 2023

Prior to the 1990s, prolonged postoperative intubation and admission to the intensive care unit was considered the standard of care following liver transplantation. Advocates of this practice speculated that this time allowed patients to recover from the stress of major surgery and allowed their clinicians to optimize the recipients’ hemodynamics. As evidence in the cardiac surgical literature on the feasibility of early extubation grew, clinicians began applying these principles to liver transplant recipients. Further, some centers also began challenging the dogma that patients need to be cared for in the intensive care unit following liver transplantation and instead transferred patients to the floor or stepdown units immediately following surgery, a technique known as “fast-track” liver transplantation. This article aims to provide a history of early extubation for liver transplant recipients and offer practical advice on how to select patients that may be able to bypass the intensive care unit and be recovered in a non-traditional manner.
Unexpected Uterine Rupture—A Case Report, Review of the Literature and Clinical Suggestions
Authors: Flis Wojciech , Socha Maciej W. , Wartęga Mateusz , Cudnik Rafał
Published: May 2023

Background and Objectives: Women with a history of cesarean section are a high-risk group because they are likely to develop uterine rupture during their next pregnancy. Current evidence suggests that a vaginal birth after cesarean section (VBAC) is associated with lower maternal mortality and morbidity than elective repeat cesarean delivery (ERCD). Additionally, research suggests that uterine rupture can occur in 0.47% of cases of trial of labor after cesarean section (TOLAC). Case Description: A healthy 32-year-old woman at 41 weeks of gestation, in her fourth pregnancy, was admitted to the hospital due to a dubious CTG record. Following this, the patient gave birth vaginally, underwent a cesarean section, and successfully underwent a VBAC. Due to her advanced gestational age and favorable cervix, the patient qualified for a trial of vaginal labor (TOL). During labor induction, she displayed a pathological CTG pattern and presented symptoms such as abdominal pain and heavy vaginal bleeding. Suspecting a violent uterine rupture, an emergency cesarean section was performed. The presumed diagnosis was confirmed during the procedure—a full-thickness rupture of the pregnant uterus was found. The fetus was delivered without signs of life and successfully resuscitated after 3 min. The newborn girl of weight 3150 g had an Apgar score of 0/6/8/8 at 1, 3, 5, and 10 min. The uterine wall rupture was closed with two layers of sutures. The patient was discharged 4 days after the cesarean section without significant complications, with a healthy newborn girl. Conclusions: Uterine rupture is a rare but severe obstetric emergency and can be associated with maternal and neonatal fatal outcomes. The risk of uterine rupture during a TOLAC attempt should always be considered, even if it is a subsequent TOLAC.