bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular Vesicles Derived from Mesenchymal Stromal Cells Delivered during Hypothermic Oxygenated Machine Perfusion Repair Ischemic/Reperfusion Damage of Kidneys from Extended Criteria Donors
Authors: Rampino Teresa , Gregorini Marilena , Germinario Giuliana , Pattonieri Eleonora Francesca , Erasmi Fulvia , Grignano Maria Antonietta , Bruno Stefano , Alomari Esra , Bettati Stefano , Asti Annalia , Ramus Marina , De Amici Mara , Testa Giorgia , Bruno Stefania , Ceccarelli Gabriele , Serpieri Nicoletta , Libetta Carmelo , Sepe Vincenzo , Blasevich Flavia , Odaldi Federica , Maroni Lorenzo , Vasuri Francesco , La Manna Gaetano , Ravaioli Matteo
Published: February 2022

The poor availability of kidney for transplantation has led to a search for new strategies to increase the donor pool. The main option is the use of organs from extended criteria donors. We evaluated the effects of hypothermic oxygenated perfusion (HOPE) with and without extracellular vesicles (EV) derived from mesenchymal stromal cells on ischemic/reperfusion injury of marginal kidneys unsuitable for transplantation. For normothermic reperfusion (NR), we used artificial blood as a substitute for red blood cells. We evaluated the global renal ischemic dam-age score (GRS), analyzed the renal ultrastructure (RU), cytochrome c oxidase (COX) IV-1 (a mitochondrial distress marker), and caspase-3 renal expression, the tubular cell proliferation index, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) tissue levels, and effluent lactate and glucose levels. HOPE+EV kidneys had lower GRS and better RU, higher COX IV-1 expression and HGF and VEGF levels and lower caspase-3 expression than HOPE kidneys. During NR, HOPE+EV renal effluent had lower lactate release and higher glucose levels than HOPE renal effluent, suggesting that the gluconeogenesis system in HOPE+EV group was pre-served. In conclusion, EV delivery during HOPE can be considered a new organ preservation strategy for increasing the donor pool and improving transplant outcome.
Role of Epicardial Adipose Tissue in Cardiovascular Diseases: A Review
Authors: Konwerski Michał , Gąsecka Aleksandra , Opolski Grzegorz , Grabowski Marcin , Mazurek Tomasz
Published: February 2022

Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Epicardial adipose tissue (EAT) is defined as a fat depot localized between the myocardial surface and the visceral layer of the pericardium and is a type of visceral fat. EAT is one of the most important risk factors for atherosclerosis and cardiovascular events and a promising new therapeutic target in CVDs. In health conditions, EAT has a protective function, including protection against hypothermia or mechanical stress, providing myocardial energy supply from free fatty acid and release of adiponectin. In patients with obesity, metabolic syndrome, or diabetes mellitus, EAT becomes a deleterious tissue promoting the development of CVDs. Previously, we showed an adverse modulation of gene expression in pericoronary adipose tissue in patients with coronary artery disease (CAD). Here, we summarize the currently available evidence regarding the role of EAT in the development of CVDs, including CAD, heart failure, and atrial fibrillation. Due to the rapid development of the COVID-19 pandemic, we also discuss data regarding the association between EAT and the course of COVID-19. Finally, we present the potential therapeutic possibilities aiming at modifying EAT’s function. The development of novel therapies specifically targeting EAT could revolutionize the prognosis in CVDs.
An Integrated Taxonomic Approach Points towards a Single-Species Hypothesis for Santolina (Asteraceae) in Corsica and Sardinia
Authors: De Giorgi Paola , Giacò Antonio , Astuti Giovanni , Minuto Luigi , Varaldo Lucia , De Luca Daniele , De Rosa Alessandro , Bacchetta Gianluigi , Sarigu Marco , Peruzzi Lorenzo
Published: February 2022

Santolina is a plant genus of dwarf aromatic shrubs that includes about 26 species native to the western Mediterranean Basin. In Corsica and Sardinia, two of the main islands of the Mediterranean, Santolina corsica (tetraploid) and S. insularis (hexaploid) are reported. Along with the cultivated pentaploid S. chamaecyparissus, these species form a group of taxa that is hard to distinguish only by morphology. Molecular (using ITS, trnH-psbA, trnL-trnF, trnQ-rps16, rps15-ycf1, psbM-trnD, and trnS-trnG), cypsela morpho-colorimetric, morphometric, and niche similarity analyses were conducted to investigate the diversity of plants belonging to this species group. Our results confute the current taxonomic hypothesis and suggest considering S. corsica and S. insularis as a single species. Moreover, molecular and morphometric results highlight the strong affinity between S. chamaecyparissus and the Santolina populations endemic to Corsica and Sardinia. Finally, the populations from south-western Sardinia, due to their high differentiation in the studied plastid markers and the different climatic niche with respect to all the other populations, could be considered as an evolutionary significant unit.
Glucose- and Non-Glucose-Induced Mitochondrial Dysfunction in Diabetic Kidney Disease
Authors: Ito Marie , Gurumani Margaret Zvido , Merscher Sandra , Fornoni Alessia
Published: February 2022

Mitochondrial dysfunction plays an important role in the pathogenesis and progression of diabetic kidney disease (DKD). In this review, we will discuss mitochondrial dysfunction observed in preclinical models of DKD as well as in clinical DKD with a focus on oxidative phosphorylation (OXPHOS), mitochondrial reactive oxygen species (mtROS), biogenesis, fission and fusion, mitophagy and urinary mitochondrial biomarkers. Both glucose- and non-glucose-induced mitochondrial dysfunction will be discussed. In terms of glucose-induced mitochondrial dysfunction, the energetic shift from OXPHOS to aerobic glycolysis, called the Warburg effect, occurs and the resulting toxic intermediates of glucose metabolism contribute to DKD-induced injury. In terms of non-glucose-induced mitochondrial dysfunction, we will review the roles of lipotoxicity, hypoxia and vasoactive pathways, including endothelin-1 (Edn1)/Edn1 receptor type A signaling pathways. Although the relative contribution of each of these pathways to DKD remains unclear, the goal of this review is to highlight the complexity of mitochondrial dysfunction in DKD and to discuss how markers of mitochondrial dysfunction could help us stratify patients at risk for DKD.
Early-Onset Glaucoma in egl1 Mice Homozygous for Pitx2 Mutation
Authors: Kodati Bindu , Merchant Shawn A. , Millar J. Cameron , Liu Yang
Published: February 2022

Mutations in PITX2 cause Axenfeld–Rieger syndrome, with congenital glaucoma as an ocular feature. The egl1 mouse strain carries a chemically induced Pitx2 mutation and develops early-onset glaucoma. In this study, we characterized the glaucomatous features in egl1 mice. The eyes of egl1 and C57BL/6J control mice were assessed by slit lamp examination, total aqueous humor outflow facility, intraocular pressure (IOP) measurement, pattern electroretinography (PERG) recording, and histologic and immunohistochemistry assessment beginning at 3 weeks and up to 12 months of age. The egl1 mice developed elevated IOP as early as 4 weeks old. The IOP elevation was variable and asymmetric within and between the animals. The aqueous humor outflow facility was significantly reduced in 12-month-old animals. PERG detected a decreased response at 2 weeks after the development of IOP elevation. Retinal ganglion cell (RGC) loss was detected after 8 weeks of IOP elevation. Slit lamp and histologic evaluation revealed corneal opacity, iridocorneal adhesions (anterior synechiae), and ciliary body atrophy in egl1 mice. Immunohistochemistry assessment demonstrated glial cell activation and RGC axonal injury in response to IOP elevation. These results show that the eyes of egl1 mice exhibit anterior segment dysgenesis and early-onset glaucoma. The egl1 mouse strain may represent a useful model for the study of congenital glaucoma.
Laminin Triggers Neutrophil Extracellular Traps (NETs) and Modulates NET Release Induced by Leishmania amazonensis
Authors: Silva-Oliveira Gustavo , Linhares-Lacerda Leandra , Mattos Thayana R. F. , Sanches Camila , Coelho-Sampaio Tatiana , Riederer Ingo , Saraiva Elvira M.
Published: February 2022

Neutrophils are recruited from the blood and transmigrate through the endothelium to reach tissues, where they are prone to respond through different mechanisms, including the release of neutrophil extracellular traps (NETs). These responses occur in close contact with proteins from the basement membrane and extracellular matrix, where laminins are abundant. Thus, we investigated the interactions between neutrophils and different laminin (LM) isoforms and analyzed the induction of NETs. We showed that neutrophils stimulated with LM isoforms 111, 211, 332, 411, 421, and 511 released NETs. The same occurred when neutrophils interacted with polymerized LMs 111, 411, and 511. LM-induced NETs were partially inhibited by pretreatment of neutrophils with an anti-α6 integrin antibody. Furthermore, NETs triggered by laminins were dependent on elastase and peptidylarginine deiminase (PAD)-4, enzymes that participate in chromatin decondensation. We also found that LMs 411 and LM 511 potentiated the NET release promoted by promastigotes of the protozoan parasite Leishmania, and that NETs stimulated by LMs alone display leishmanicidal activity. The ability of LM to induce NET release may have potential implications for the course of inflammation or infection.
Alcohol Use and Prefrontal Cortex Volume Trajectories in Young Adults with Mood Disorders and Associated Clinical Outcomes
Authors: Kirsch Dylan E. , Tretyak Valeria , Le Vanessa , Huffman Ansley , Fromme Kim , Strakowski Stephen M. , Lippard Elizabeth T.C.
Published: February 2022

(1) Background: Alcohol use in the course of mood disorders is associated with worse clinical outcomes. The mechanisms by which alcohol use alters the course of illness are unclear but may relate to prefrontal cortical (PFC) sensitivity to alcohol. We investigated associations between alcohol use and PFC structural trajectories in young adults with a mood disorder compared to typically developing peers. (2) Methods: 41 young adults (24 with a mood disorder, agemean = 21 ± 2 years) completed clinical evaluations, assessment of alcohol use, and two structural MRI scans approximately one year apart. Freesurfer was used to segment PFC regions of interest (ROIs) (anterior cingulate, orbitofrontal cortex, and frontal pole). Effects of group, alcohol use, time, and interactions among these variables on PFC ROIs at baseline and follow-up were modeled. Associations were examined between alcohol use and longitudinal changes in PFC ROIs with prospective mood. (3) Results: Greater alcohol use was prospectively associated with decreased frontal pole volume in participants with a mood disorder, but not typically developing comparison participants (time-by-group-by-alcohol interaction; p = 0.007); however, this interaction became a statistical trend in a sensitivity analysis excluding one outlier in terms of alcohol use. Greater alcohol use and a decrease in frontal pole volume related to longer duration of major depression during follow-up (p’s < 0.05). (4) Conclusion: Preliminary findings support more research on alcohol use, PFC trajectories, and depression recurrence in young adults with a mood disorder including individuals with heavier drinking patterns.
PET Imaging in Neuro-Oncology: An Update and Overview of a Rapidly Growing Area
Authors: Verger Antoine , Kas Aurélie , Darcourt Jacques , Guedj Eric
Published: February 2022

PET plays an increasingly important role in the management of brain tumors. This review outlines currently available PET radiotracers and their respective indications. It specifically focuses on 18F-FDG, amino acid and somatostatin receptor radiotracers, for imaging gliomas, meningiomas, primary central nervous system lymphomas as well as brain metastases. Recent advances in radiopharmaceuticals, image analyses and translational applications to therapy are also discussed. The objective of this review is to provide a comprehensive overview of PET imaging’s potential in neuro-oncology as an adjunct to brain MRI for all medical professionals implicated in brain tumor diagnosis and care.
The Impact of a Preoperative Staging System on Accurate Prediction of Prognosis in Intrahepatic Cholangiocarcinoma
Authors: Kosaka Hisashi , Ueno Masaki , Komeda Koji , Hokuto Daisuke , Iida Hiroya , Hirokawa Fumitoshi , Matsui Kosuke , Sekimoto Mitsugu , Kaibori Masaki
Published: February 2022

Background: Non-invasive biomarkers detected preoperatively are still inadequate for treatment decision making for patients with intrahepatic cholangiocarcinoma (ICC). In this study, we analyzed preoperative findings to establish a novel preoperative staging system (PRE-Stage) for patients with ICC. Methods: The clinical data of 227 consecutive patients with histologically confirmed ICC following hepatectomy at five university hospitals were analyzed. Results: Cox proportional hazards regression analysis of survival revealed that a CRP–albumin–lymphocyte index < 3, central tumor location, and CA19-9 level > 40 U/mL were prognostic factors among the preoperatively obtained clinical findings (hazard ratios (HRs) of all three factors for disease-specific survival (DSS) and disease-free survival (DFS: 2.4–3.3 and 1.7–2.9; all p < 0.05). The PRE-Stage was developed using these three prognostic factors, and it was able to significantly predict DSS and DFS when the patients were stratified into four stages (p < 0.05). In addition, the PRE-Stage resulted in similar HRs as those of the Liver Cancer Study Group of Japan (LCSGJ) stage (HRs for DSS: PRE-Stage, 1.985; LCSGJ stage, 1.923; HRs for DFS: LCSGJ stage, 1.909, and PRE-Stage, 1.623, all p < 0.05). Conclusion: The PRE-Stage demonstrated similar accuracy in predicting the prognosis of ICC as that of the LCSGJ stage, which is based on postoperative findings. The PRE-Stage may contribute to appropriate treatment decision making.
Reduced Expression of Annexin A6 Induces Metabolic Reprogramming That Favors Rapid Fatty Acid Oxidation in Triple-Negative Breast Cancer Cells
Authors: Williams Stephen D. , Sakwe Amos M.
Published: February 2022

The ability of cancer cells to alter their metabolism is one of the major mechanisms underlying rapid tumor progression and/or therapeutic resistance in solid tumors, including the hard-to-treat triple-negative breast cancer (TNBC) subtype. Here, we assessed the contribution of the tumor suppressor, Annexin A6 (AnxA6), in the metabolic adaptation of basal-like (AnxA6-low) versus mesenchymal-like (AnxA6-high), as well as in lapatinib-resistant TNBC cells. Using model basal-like and mesenchymal-like TNBC cell lines, we show that TNBC cells also exhibit metabolic heterogeneity. The downregulation of AnxA6 in TNBC cells generally attenuated mitochondrial respiration, glycolytic flux, and cellular ATP production capacity resulting in a quiescent metabolic phenotype. We also show that AnxA6 depletion in mesenchymal-like TNBC cells was associated with a rapid uptake and mitochondrial fatty acid oxidation and diminished lipid droplet accumulation and altered the lipogenic metabolic phenotype of these cells to a lypolytic metabolic phenotype. The overexpression or chronic lapatinib-induced upregulation of AnxA6 in AnxA6-low TNBC cells reversed the quiescent/lypolytic phenotype to a more lipogenic/glycolytic phenotype with gluconeogenic precursors as additional metabolites. Collectively, these data suggest that the expression status of AnxA6 in TNBC cells underlies distinct metabolic adaptations of basal-like and mesenchymal-like TNBC subsets in response to cellular stress and/or therapeutic intervention and suggest AnxA6 as a biomarker for metabolic subtyping of TNBC subsets.
Slow-Cycling Cells in Glioblastoma: A Specific Population in the Cellular Mosaic of Cancer Stem Cells
Authors: Yang Changlin , Tian Guimei , Dajac Mariana , Doty Andria , Wang Shu , Lee Ji-Hyun , Rahman Maryam , Huang Jianping , Reynolds Brent A. , Sarkisian Matthew R. , Mitchell Duane , Deleyrolle Loic P.
Published: February 2022

Glioblastoma (GBM) exhibits populations of cells that drive tumorigenesis, treatment resistance, and disease progression. Cells with such properties have been described to express specific surface and intracellular markers or exhibit specific functional states, including being slow-cycling or quiescent with the ability to generate proliferative progenies. In GBM, each of these cellular fractions was shown to harbor cardinal features of cancer stem cells (CSCs). In this study, we focus on the comparison of these cells and present evidence of great phenotypic and functional heterogeneity in brain cancer cell populations with stemness properties, especially between slow-cycling cells (SCCs) and cells phenotypically defined based on the expression of markers commonly used to enrich for CSCs. Here, we present an integrative analysis of the heterogeneity present in GBM cancer stem cell populations using a combination of approaches including flow cytometry, bulk RNA sequencing, and single cell transcriptomics completed with functional assays. We demonstrated that SCCs exhibit a diverse range of expression levels of canonical CSC markers. Importantly, the property of being slow-cycling and the expression of these markers were not mutually inclusive. We interrogated a single-cell RNA sequencing dataset and defined a group of cells as SCCs based on the highest score of a specific metabolic signature. Multiple CSC groups were determined based on the highest expression level of CD133, SOX2, PTPRZ1, ITGB8, or CD44. Each group, composed of 22 cells, showed limited cellular overlap, with SCCs representing a unique population with none of the 22 cells being included in the other groups. We also found transcriptomic distinctions between populations, which correlated with clinicopathological features of GBM. Patients with strong SCC signature score were associated with shorter survival and clustered within the mesenchymal molecular subtype. Cellular diversity amongst these populations was also demonstrated functionally, as illustrated by the heterogenous response to the chemotherapeutic agent temozolomide. In conclusion, our study supports the cancer stem cell mosaicism model, with slow-cycling cells representing critical elements harboring key features of disseminating cells.
DNA Repair Enzyme Poly(ADP-Ribose) Polymerase 1/2 (PARP1/2)-Targeted Nuclear Imaging and Radiotherapy
Authors: Nguyen Nghia T. , Pacelli Anna , Nader Michael , Kossatz Susanne
Published: February 2022

Since it was discovered that many tumor types are vulnerable to inhibition of the DNA repair machinery, research towards efficient and selective inhibitors has accelerated. Amongst other enzymes, poly(ADP-ribose)-polymerase 1 (PARP1) was identified as a key player in this process, which resulted in the development of selective PARP inhibitors (PARPi) as anti-cancer drugs. Most small molecule PARPi’s exhibit high affinity for both PARP1 and PARP2. PARPi are under clinical investigation for mono- and combination therapy in several cancer types and five PARPi are now clinically approved. In parallel, radiolabeled PARPi have emerged for non-invasive imaging of PARP1 expression. PARP imaging agents have been suggested as companion diagnostics, patient selection, and treatment monitoring tools to improve the outcome of PARPi therapy, but also as stand-alone diagnostics. We give a comprehensive overview over the preclinical development of PARP imaging agents, which are mostly based on the PARPi olaparib, rucaparib, and recently also talazoparib. We also report on the current status of clinical translation, which involves a growing number of early phase trials. Additionally, this work provides an insight into promising approaches of PARP-targeted radiotherapy based on Auger and α-emitting isotopes. Furthermore, the review covers synthetic strategies for PARP-targeted imaging and therapy agents that are compatible with large scale production and clinical translation.
Delay Discounting as a Potential Therapeutic Target for Weight Loss in Breast Cancer Survivors
Authors: Sukumar Jasmine S. , Vaughn Jennifer E. , Tegge Allison , Sardesai Sagar , Lustberg Maryam , Stein Jeffrey
Published: February 2022

Obesity in breast cancer (BC) survivors is associated with increased mortality. Delay discounting (DD) is a behavioral economic measure of how individuals value future outcomes. Higher DD correlates with obesity in the general population. Valuation of the future may be associated with obesity differently in cancer survivors. This study evaluated the relationship between DD and obesity in BC survivors. We report an exploratory analysis assessing cross-sectional associations between DD, BMI, and lifestyle behaviors (vegetable and fruit consumption, exercise) related to obesity in 89 women with hormone receptor positive non-metastatic BC. Multivariate linear regression analysis examined demographic and lifestyle behavior variables associated with both BMI and DD. Greater willingness to wait for larger, delayed rewards (lower DD) was significantly associated with lower BMI (standardized beta = −0.32; p < 0.01), independent of age, race, income, time since diagnosis, and menopausal status. There was no significant association between DD and fruit consumption or exercise frequency. Vegetable consumption was significantly associated with lower DD (standardized beta = 0.24; p < 0.05). Higher DD is associated with obesity and decreased frequency of vegetable consumption in BC survivors. Future studies should investigate DD as a therapeutic target for behavioral interventions to facilitate weight loss and promote longevity in this population.
Line-Field Confocal Optical Coherence Tomography: A New Tool for the Differentiation between Nevi and Melanomas?
Authors: Schuh Sandra , Ruini Cristel , Perwein Maria Katharina Elisabeth , Daxenberger Fabia , Gust Charlotte , Sattler Elke Christina , Welzel Julia
Published: February 2022

Until now, the clinical differentiation between a nevus and a melanoma is still challenging in some cases. Line-field confocal optical coherence tomography (LC-OCT) is a new tool with the aim to change that. The aim of the study was to evaluate LC-OCT for the discrimination between nevi and melanomas. A total of 84 melanocytic lesions were examined with LC-OCT and 36 were also imaged with RCM. The observers recorded the diagnoses, and the presence or absence of the 18 most common imaging parameters for melanocytic lesions, nevi, and melanomas in the LC-OCT images. Their confidence in diagnosis and the image quality of LC-OCT and RCM were evaluated. The most useful criteria, the sensitivity and specificity of LC-OCT vs. RCM vs. histology, to differentiate a (dysplastic) nevus from a melanoma were analyzed. Good image quality correlated with better diagnostic performance (Spearman correlation: 0.4). LC-OCT had a 93% sensitivity and 100% specificity compared to RCM (93% sensitivity, 95% specificity) for diagnosing a melanoma (vs. all types of nevi). No difference in performance between RCM and LC-OCT was observed (McNemar’s p value = 1). Both devices falsely diagnosed dysplastic nevi as non-dysplastic (43% sensitivity for dysplastic nevus diagnosis). The most significant criteria for diagnosing a melanoma with LC-OCT were irregular honeycombed patterns (92% occurrence rate; 31.7 odds ratio (OR)), the presence of pagetoid spread (89% occurrence rate; 23.6 OR) and the absence of dermal nests (23% occurrence rate, 0.02 OR). In conclusion LC-OCT is useful for the discrimination between melanomas and nevi.
Expression of miR-24-1-5p in Tumor Tissue Influences Prostate Cancer Recurrence: The PROCA-life Study
Authors: Stikbakke Einar , Wilsgaard Tom , Haugnes Hege Sagstuen , Pedersen Mona Irene , Knutsen Tore , Støyten Martin , Giovannucci Edward , Eggen Anne Elise , Thune Inger , Richardsen Elin
Published: February 2022

The role of miR-24-1-5p and its prognostic implications associated with prostate cancer are mainly unknown. In a population-based cohort, the Prostate Cancer Study throughout life (PROCA-life), all men had a general health examination at study entry and were followed between 1994 and 2016. Patients with available tissue samples after a prostatectomy with curative intent were identified (n = 189). The tissue expression of miR-24-1-5p in prostate cancer was examined by in situ hybridization (ISH) in tissue microarray (TMA) blocks by semi-quantitative scoring by two independent investigators. Multivariable Cox regression models were used to study the associations between miR-24-1-5p expression and prostate cancer recurrence. The prostate cancer patients had a median age of 65.0 years (range 47–75 years). The Cancer of the Prostate Risk Assessment Postsurgical Score, International Society of Urological Pathology grade group, and European Association of Urology Risk group were all significant prognostic factors for five-year recurrence-free survival (p < 0.001). Prostate cancer patients with a high miR-24-1-5p expression (≥1.57) in the tissue had a doubled risk of recurrence compared to patients with low expression (HR 1.99, 95% CI 1.13–3.51). Our study suggests that a high expression of miR-24-1-5p is associated with an increased risk of recurrence of prostate cancer after radical prostatectomy, which points to the potential diagnostic and therapeutic value of detecting miR-24-1-5p in prostate cancer cases.
Paclitaxel Induces Epidermal Molecular Changes and Produces Subclinical Alterations in the Skin of Gynecological Cancer Patients
Authors: Montero Paula , Pérez-Leal Martín , Pérez-Fidalgo Jose Alejandro , Sanz Celia , Estornut Cristina , Roger Inés , Milara Javier , Cervantes Andrés , Cortijo Julio
Published: February 2022

Background: Paclitaxel is a microtubule-stabilizing chemotherapeutic agent. Despite its widespread use, it damages healthy tissues such as skin. The goal of this study was to prove that the real impact of paclitaxel-induced skin toxicity could be underestimated because the adverse events might appear asymptomatic. Methods: Gynecological cancer patients were recruited. Skin parameters measurements were taken after three and six paclitaxel cycles. Measurements were conducted using specific probes which measure hydration, transepidermal water loss (TEWL), sebum, elasticity and firmness, erythema, roughness, smoothness, skin thickness, and desquamation levels. Further, a 3D epidermis model was incubated with paclitaxel to analyze gene and protein expression of aquaporin 3, collagen type 1, elastin, and fibronectin. Results: Paclitaxel induced alterations in the skin parameters with no visible clinical manifestations. Gynecological cancer patients under paclitaxel treatment had a decrease in hydration, TEWL, sebum, elasticity, and thickness of the skin, while erythema, roughness, and desquamation were increased. The molecular markers, related to hydration and the support of the skin layers, and analyzed in the 3D epidermis model, were decreased. Conclusions: Results suggest that paclitaxel modifies gene and protein expression of skin-related molecular markers, and impairs different physical, physiological, and biomechanical properties of the skin of cancer patients at a subclinical level.
An Insight into the Structural Requirements and Pharmacophore Identification of Carbonic Anhydrase Inhibitors to Combat Oxidative Stress at High Altitudes: An In-Silico Approach
Authors: Ali Amena , Ali Abuzer , Warsi Musarrat Husain , Rahman Mohammad Akhlaquer , Ahsan Mohamed Jawed , Azam Faizul
Published: February 2022

Carbonic anhydrases (CA) inhibitory action could be linked to the treatment of a number of ailments, including cancer, osteoporosis, glaucoma, and several neurological problems. For the development of effective CA inhibitors, a variety of heterocyclic rings have been investigated. Furthermore, at high altitudes, oxygen pressure drops, resulting in the formation of reactive oxygen and nitrogen species, and CA inhibitors having role in combating this oxidative stress. Acetazolamide contains thiadiazole ring, which has aroused researchers’ interest because of its CA inhibitory action. In the present study, we used a number of drug design tools, such as pharmacophore modeling, 3D QSAR, docking, and virtual screening on twenty-seven 1,3,4-thiadiazole derivatives that have been described as potential CA inhibitors in the literature. An atom-based 3D-QSAR analysis was carried out to determine the contribution of individual atoms to model generation, while a pharmacophore mapping investigation was carried out to find the common unique pharmacophoric properties required for biological activity. The coefficient of determination for both the training and test sets were statistically significant in the generated model. The best QSAR model was chosen based on the values of R2 (0.8757) and Q2 (0.7888). A molecular docking study was also conducted against the most potent analogue 4m, which has the highest SP docking score (−5.217) (PDB ID: 6g3v). The virtual screening revealed a number of promising compounds. The screened compound ZINC77699643 interacted with the amino acid residues, Pro201 and Thr199, in the virtual screening study (PDB ID: 6g3v). These interactions demonstrated the significance of the CA inhibitory activity of the compound. Furthermore, ADME study revealed useful information regarding compound’s drug-like properties. Therefore, the findings of the present investigation could aid in the development of more potent CA inhibitors, which could benefit the treatment of oxidative stress at high altitudes.
Fuzzy Logic Decision Support System to Predict Peaches Marketable Period at Highest Quality
Authors: Magalhães Bianca , Gaspar Pedro Dinis , Corceiro Ana , João Luzolo , Bumba César
Published: February 2022

Food waste occurs from harvesting to consumption. Applying procedures and technologies, changing attitudes, and promoting awareness have positive social, economic, and environmental impacts that can contribute to reducing food waste. The paper presents a decision support system (DSS) to predict the quality evolution of fruits and vegetables, particularly of peaches, and estimate its commercialization period at the highest overall perceived quality by consumers, thus contributing to reducing food waste. The Fuzzy Logic DSS predicts the evolution of the physical-chemical parameters of peaches (hardness, soluble solids content, and acidity) depending on the cultivar (Royal Summer and Royal Time), storage time, and temperature. As the range of the values of these physical-chemical parameters of peaches that consumers perceive to be at their highest quality are known, the DSS predicts the marketable period in days. Case studies were developed to analyze the influence of each physical-chemical parameter on the commercialization days (number and time to start). It is concluded that temperature is the most important parameter for fruit conservation. A low value of conservation temperature allows for the significant extension of the time that peaches can be sold at the highest quality. Hardness is used to determine the harvest date since it is an index of fruit ripeness. The same conclusion is obtained for the influence of the soluble solids content. The influence of acidity on marketable days is less than the other physical-chemical parameters. This DSS helps retailers to sell their peaches at the highest quality with benefits for all parties. It also helps in the decision-making concerning the actions to take when fruits are reaching the end of their highest quality by predicting the range of the commercialization days. This formulation can be extended to other fruits and vegetables and in the last instance contribute to the reduction of food loss and waste, consequently promoting social, economic, and environmental aspects of our daily life.
Publisher’s Note: We Changed Page Numbers to Article Numbers for Articles Published in Clinics and Practice Volumes 1–10
Authors:   Clinics and Practice Editorial Office
Published: February 2022

Clinics and Practice [...]
Literature Review on MOOCs on Sensory (Olfactory) Learning
Authors: Limone Pierpaolo , Pati Sandra , Toto Giusi Antonia , Di Fuccio Raffaele , Baiano Antonietta , Lopriore Giuseppe
Published: February 2022

Massive Open Online Courses (MOOCs) have been described as a “next development of networked learning”, and they have the potential to mediate sensory learning. To understand this phenomenon, the present systematic review examines the research techniques, subjects, and trends of MOOC research on sensory learning, in order to provide a thorough understanding of the MOOC relevant to sensory (olfactory) learning phenomena by evaluating 65 (four studies are about multisensorial learning and 61 are about multisensorial empirical MOOCs researches) empirical MOOC studies published between 2008 and 2021 by searching through databases: PubMed, Scopus, Web of Science, and Google Scholar. The results indicated that most studies were based on quantitative research methods followed by mixed research methods and the qualitative research approaches; most of the studies were surveys, followed by platform databases and interviews; almost half of the studies were conducted using at least two methods for data collection: survey and interviews; most were replicated. The most highlighted subjects included student retention, learning experience, social learning, and engagement. Implications and studies into the future have been considered in order to obtain a more evolved understanding of the acquisition of knowledge through the senses.
BA.1 Omicron Variant of SARS-CoV-2: First Case Reported in Calabria Region, Italy
Authors: Peronace Cinzia , Tallerico Rossana , Colosimo Manuela , De Fazio Marco , Pasceri Federica , Talotta Ilenia , Panduri Giuseppina , Pintomalli Letizia , Oteri Rosaria , Calantoni Valeria , Fiorillo Maria Teresa , Gallelli Luca , Cione Erika , Minchella Pasquale
Published: February 2022

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. Several variants of concern (VOCs) have been identified so far. Recently, the B.1.1.529 (Omicron) variant of SARS-CoV-2 spread rapidly worldwide. We describe the first case of the Omicron genetic lineage BA.1 in our region. The patient is a physician who traveled to Johannesburg (South Africa) and returned to Reggio Calabria (Italy). He underwent a SARS-CoV-2 screening before leaving—a required procedure where travelers present a negative PCR test one-day prior to departing. Three days after arriving in Italy, he started experiencing cold symptoms. Clinically, he was without fever or severe respiratory symptoms and reported suffering from a cold and sore throat. The nasopharyngeal swab specimen was tested by TaqPath COVID-19 RT-PCR and sequenced by Sanger sequencing, and next-generation sequencing (NGS) data were processed with their relative software. A peculiar drop-off of the S gene was obtained with TaqPath COVID-19 RT-PCR. S gene mutations indicative of the Omicron variant were obtained with both sequencing methods, pointing out 17 mutations in the 29 recognized by Sanger and the 28 recognized by NGS.
Point of Care Molecular Testing: Community-Based Rapid Next-Generation Sequencing to Support Cancer Care
Authors: Sheffield Brandon S. , Beharry Andrea , Diep Joanne , Perdrizet Kirstin , Iafolla Marco A. J. , Raskin William , Dudani Shaan , Brett Mary Anne , Starova Blerta , Olsen Brian , Cheema Parneet K.
Published: February 2022

Purpose: Biomarker data are critical to the delivery of precision cancer care. The average turnaround of next-generation sequencing (NGS) reports is over 2 weeks, and in-house availability is typically limited to academic centers. Lengthy turnaround times for biomarkers can adversely affect outcomes. Traditional workflows involve moving specimens through multiple facilities. This study evaluates the feasibility of rapid comprehensive NGS using the Genexus integrated sequencer and a novel streamlined workflow in a community setting. Methods: A retrospective chart review was performed to assess the early experience and performance characteristics of a novel approach to biomarker testing at a large community center. This approach to NGS included an automated workflow utilizing the Genexus integrated sequencer, validated for clinical use. NGS testing was further integrated within a routine immunohistochemistry (IHC) service, utilizing histotechnologists to perform technical aspects of NGS, with results reported directly by anatomic pathologists. Results: Between October 2020 and October 2021, 578 solid tumor samples underwent genomic profiling. Median turnaround time for biomarker results was 3 business days (IQR: 2–5). Four hundred eighty-one (83%) of the cases were resulted in fewer than 5 business days, and 66 (11%) of the cases were resulted simultaneously with diagnosis. Tumor types included lung cancer (310), melanoma (97), and colorectal carcinoma (68), among others. NGS testing detected key driver alterations at expected prevalence rates: lung EGFR (16%), ALK (3%), RET (1%), melanoma BRAF (43%), colorectal RAS/RAF (67%), among others. Conclusion: This is the first study demonstrating clinical implementation of rapid NGS. This supports the feasibility of automated comprehensive NGS performed and interpreted in parallel with diagnostic histopathology and immunohistochemistry. This novel approach to biomarker testing offers considerable advantages to clinical cancer care.
Current Perspectives on the Importance of Pathological Features in Prognostication and Guidance of Adjuvant Chemotherapy in Colon Cancer
Authors: Chen Kabytto , Wang Henry , Collins Geoffrey , Hollands Emma , Law Irene Yuen Jing , Toh James Wei Tatt
Published: February 2022

There is not a clear consensus on which pathological features and biomarkers are important in guiding prognosis and adjuvant therapy in colon cancer. The Pathology in Colon Cancer, Prognosis and Uptake of Adjuvant Therapy (PiCC UP) Australia and New Zealand questionnaire was distributed to colorectal surgeons, medical oncologists and pathologists after institutional board approval. The aim of this study was to understand current specialist attitudes towards pathological features in the prognostication of colon cancer and adjuvant therapy in stage II disease. A 5-scale Likert score was used to assess attitudes towards 23 pathological features for prognosis and 18 features for adjuvant therapy. Data were analysed using a rating scale and graded response model in item response theory (IRT) on STATA (Stata MP, version 15; StataCorp LP). One hundred and sixty-four specialists (45 oncologists, 86 surgeons and 33 pathologists) participated. Based on IRT modelling, the most important pathological features for prognosis in colon cancer were distant metastases, lymph node metastases and liver metastases. Other features seen as important were tumour rupture, involved margin, radial margin, CRM, lymphovascular invasion and grade of differentiation. Size of tumour, location, lymph node ratio and EGFR status were considered less important. The most important features in decision making for adjuvant therapy in stage II colon cancer were tumour rupture, lymphovascular invasion and microsatellite instability. BRAF status, size of tumour, location, tumour budding and tumour infiltrating lymphocytes were factored as lesser importance. Biomarkers such as CDX2, EGFR, KRAS and BRAF status present areas for further research to improve precision oncology. This study provides the most current status on the importance of pathological features in prognostication and recommendations for adjuvant therapy in Australia and New Zealand. Results of this nationwide study may be useful to help in guiding prognosis and adjuvant treatment in colon cancer.
Mitogenomics and the Global Dispersion of Vespula germanica: A Case Study from South Africa Shows Evidence for Two Separate Invasion Events
Authors: van Asch Barbara , Wolf Michael , Marais Inès , Daly Derek , Veldtman Ruan
Published: February 2022

Vespula germanica is currently present in all major world regions outside its native Northern Hemisphere range and poses a biological threat to the invaded ecosystems. The genetic diversity of the species is poorly described in both the native and invaded ranges, thus hampering insights into possible mechanisms of invasion. In South Africa, V. germanica was first detected in 1972, and a recent study concluded that one large or several independent invasion events had occurred. However, the high number of low-frequency haplotypes reported therein raised doubts about the quality of the data. In this study, we reassessed the haplotype diversity of V. germanica in South Africa under improved methodological conditions. New mitochondrial markers were developed using complete mitochondrial genomes of V. germanica that allowed the identification of polymorphic regions and the design of robust species-specific primers. Contrary to two previous studies, only two mitochondrial haplotypes were found in South Africa despite almost doubling the number of sampled nests. It is likely that that the number of haplotypes previously reported was overestimated due to the miscalling of nucleotide positions in the electropherograms. Furthermore, the two haplotypes found have contrasting geographic distributions, which supports the known invasion history for this species. Availability of complete mitochondrial genomes for selection of polymorphic regions and design of robust species-specific primers improved the accuracy of the assessment of V. germanica diversity in South Africa. This approach will also be valuable for studying invasive wasp populations of this and other species globally.
Genetic Variability of the Mating Recognition Gene in Populations of Brachionus plicatilis
Authors: Jezkova Ivana , Serra Manuel , Ortells Raquel , Montero Javier
Published: February 2022

The development of reproductive barriers promotes within-species divergence and is a requisite for speciation to occur. Mate recognition in the rotifer B. plicatilis is mediated through a surface glycoprotein called Mating Recognition Protein (MRP). Here we investigate the genetic variation of the mmr-b, MRP coding, gene in different natural populations of B. plicatilis from the Iberian Peninsula, that present different degree of population differentiation, with known adaptive divergence in some cases. The MRP gene consists of several nearly identical tandem repeats. We found a relatively high diversity within and among populations both in the number of repeats, as well as in the nucleotide sequence. Despite that most changes are neutral, variation that can potentially affect the protein function was found in two polymorphic sites within a repeat in some of these populations. Although being mostly subject to stabilizing selection, we have found a noticeable pattern of increasing mmr-b gene diversification correlated to increasing differences in environmental factors. The interplay between genetic differentiation, local adaptation and differentiation of the mating recognition system can lead to speciation events in nearly sympatric populations.
Two Novel Species and Two New Records within the Genus Pluteus (Agaricomycetes, Agaricales) from Thailand
Authors: Wannathes Nopparat , Suwannarach Nakarin , Khuna Surapong , Kumla Jaturong
Published: February 2022

Pluteus is a species-rich genus of saprotrophic agaric in the family Pluteaceae and is widely distributed in tropical, subtropical, and temperate areas throughout the world. Some species in this genus are threatened species according to the International Union for Conservation of Nature (IUCN) red list. During investigations of agarics in northern Thailand, four Pluteus taxa were collected. Morphological characteristics and phylogenic analyses were investigated. Two new species, namely P. chandrasikuliae and P. saisamorniae, were introduced. Pluteus chandrasikuliae is characterized by its relatively large basidiomata, an applanate, dark brown scaly pileus with a cutis pileipellis, two types of hymenial cystidia viz. irregular, as well as diverticulate cells and lageniform cells. In accordance with the phylogenetic results, this new species belongs to the Pluteus sect. Celluloderma. Moreover, P. saisamorniae is distinguished by a plano-convex with a broad umbo, dark brown minute squamules pileus, light brown lamellar edges, greyish orange stipe covered with brown granules, subglobose to broadly ellipsoid basidiospores, an abundance of thin- to thick-walled cheilocystidia and pleurocystidia, a trichohymeniderm pileipellis, and brown caulocystidia in clusters. Pluteus saisamorniae is a member of Pluteus sect. Hispidoderma. Additionally, P. losulus and P. septocystidiatus were discovered in Thailand for the first time and they belong to Pluteus sect. Pluteus. Comprehensive descriptions along with illustrations, photographs, phylogenetic trees showing their positions, and a comparison with phenetically similar taxa are provided.
Non-Gestational Ovarian Choriocarcinoma: A Rare Ovarian Cancer Subtype
Authors: Cronin Sean , Ahmed Nishat , Craig Amaranta D. , King Stephanie , Huang Min , Chu Christina S. , Mantia-Smaldone Gina M.
Published: February 2022

Non-Gestational Ovarian Choriocarcinoma (NGOC) is an extremely rare ovarian tumor, with an incidence of less than 0.6% of malignant ovarian germ cell tumors. Its close pathologic resemblance to Gestational Ovarian Choriocarcinoma (GOC), however, requires special attention as the treatments differ greatly. NGOC typically affects patients in late adolescence or early reproductive years. As a result, NGOCs are often misdiagnosed as ectopic pregnancies due to their common presentation of bleeding, abdominal pain, adnexal mass, and positive serum beta-HCG. On pathologic examination, the tumor is indistinguishable from GOC, and only after review of tissue for paternal genetic components can the diagnosis of NGOC be made. Imaging studies often show highly vascular lesions with further investigation with computer topography (CT) sometimes showing metastatic lesions in the lungs, pelvis, vagina, and liver. These lesions are often hemorrhagic and can lead to catastrophic bleeding. Treatment is vastly different from GOC; NGOC requires treatment with both surgical resection and chemotherapy, with Bleomycin, Etoposide, and Cisplatin (BEP) being the most used regimen. With correct diagnosis and treatment, patients can often receive fertility sparing treatment with long term survival.
Clear Cell Renal Cell Carcinoma Metastasized to the Ampulla of Vater 16 Years after Nephrectomy—A Rare Case
Authors: Lu Jun , Zhou Weijiang , Wei Xuyong , Wang Kai , Zhou Lixin , Xu Xiao
Published: February 2022

Although clear cell renal cell carcinoma (ccRCC) is easy to diagnose early and most can be radically resected, nearly one-third of patients still experience metastases after radical nephrectomy. The most common distant metastases sites of ccRCC are lung, bone and liver. However, periampullary metastasis of ccRCC is very rare and easy to misdiagnose. A 59-year-old male patient was hospitalized for recurrent hematochezia. He had a history of nephrectomy 16 years ago due to ccRCC. Enhanced upper abdominal computed tomography (CT) suggested a mass in the ampulla of vater, and active hemorrhage of duodenal papilla was observed by endoscopy. He underwent an emergency pancreaticoduodenectomy because endoscopic hemostasis and transcatheter arterial embolization (TAE) both failed. Intraoperatively, we found that the tumor located in the ampulla and invaded the pancreatic tissue. The operation was successful, with no postoperative complications. Postoperative pathology suggested metastatic ccRCC.