bluuebunny/crossref_metadata_2025 huggingface dataset:
Топография памятников каменного века Северо-Западного Причерноморья (на примере верхнепалеолитических стоянок анетовского региона)
Authors: Pistruil Igor
Published: May 2020

В настоящее время в степях Северо-Западного Причерноморья открыто большое количество памятников каменного века. Накопленные материалы широко используются для культурно-исторической и социально-экономической реконструкции жизни древних коллективов людей.

В связи с открытиями памятников каменного века на водоразделах в тезисном виде была выдвинута гипотеза о сезонности расположения стоянок на разных гипсометрических уровнях. Согласно данной гипотезе стоянки на высоких участках рельефа (на плато) служили для обзора местности и были кратковременными сезонными стойбищами в теплое время года. В холодное время года древние люди, вероятнее всего, жили в защищенных от ветров местах, вблизи от источников воды и топлива на террасовидных уступах берегов.

В долине р. Бакшала, около сс. Анетовка и Щуцкое, в ходе разведок было открыто около 30 памятников палеолитической эпохи. На некоторых из них (Анетовка 1, Анетовка 2, Анетовка 13, Анетовка 22) были проведены стационарные археологические исследования.

По степени изученности, известные памятники анетовского региона можно разделить на две группы: памятники с разной степенью сохранности культурного слоя (на некоторых были проведены стационарные археологические исследования) и местонахождения с подъемным материалом.

Местонахождения представлены разным количеством подъемного материала: от коллекций с десятками кремней до коллекций с сотнями изделий. На некоторых местонахождениях проведена шурфовка. Большинство местонахождений предварительно, по кремневым комплексам, можно датировать верхним палеолитом.

Памятники расположены на разных гипсометрических уровнях – от водоразделов до, практически, поймы реки, а некоторые местонахождения связаны с балочными системами. Причем, независимо от культурной принадлежности и хронологии, на разных уровнях расположены памятники с разным количеством археологических коллекций.

На настоящий момент для памятников верхнего палеолита Северо-Западного Причерноморья у нас практически нет никаких (или они очень фрагментарные) оснований (кроме поселения Анетовка 2) для выявления их сезонности. Подобная ситуация наблюдается и для памятников мезолита указанной территории, где относительно полные сведения имеются только для двух, исследованных в свое время В.Н. Станко, памятников – Белолесье и Мирное.

Проблемы сезонности, длительности обитания и подобных аспектов жизнедеятельности первобытных коллективов в степях Северо-Западного Причерноморья еще далеки до своего окончательного решения. И решаться они должны с привлечением и анализом всех доступных данных для каждого памятника индивидуально, а не простым перечислением видового состава фауны. Оперируя современной базой данных, с определенной долей вероятности, мы можем говорить только о хозяйственной специфике памятника или отдельного участка.
Добыча и обработка кремня в Донбассе в неолитическую эпоху
Authors: Kolesnik Aleksandr
Published: May 2020

В неолите заселение Донбасса было неравномерным – осваивалась преимущественно долина реки Северский Донец. В это время Донбасс становится крупным европейским центром по добыче и переработке минеральных ресурсов. В районах, богатых геологическими источниками кремня, в неолите возникали крупные производственные центры. Основное количество мастерских локализуется в междуречье Бахмута и Торца на правом берегу Северского Донца. Известны многочисленные мастерские по первичному расщеплению кремня. Продукция мастерских обеспечивала потребности местного населения и распространялась на расстояние до 200-300 км.
Системный подход в классификации керамики буджакской культуры
Authors: Ivanova Svitlana
Published: May 2020

В статье охарактеризована методика классификации керамики Буджацкой культуры Северо-Западного Причерноморья. Системный подход позволяет объективно подойти к разработке классификационных схем различных типов посуды. В работе применяется следующая иерархическая схема систематизации керамики: отдел – категория – тип – вариант.

Представлены графические классификационные схемы.
The Tail of the Late Jurassic Sauropod Giraffatitan brancai: Digital Reconstruction of Its Epaxial and Hypaxial Musculature, and Implications for Tail Biomechanics
Authors: Díez Díaz Verónica , Demuth Oliver E. , Schwarz Daniela , Mallison Heinrich
Published: May 2020

Dinosaur locomotion and biomechanics, especially of their pelvic girdles and hindlimbs, have been analyzed in numerous studies. However, detailed volumetric musculoskeletal models of their tails are rarely developed. Here, we present the first detailed three-dimensional volumetric reconstruction of the caudal epaxial and hypaxial musculature of the Late Jurassic sauropod Giraffatitan brancai, and highlight the importance and necessity of 3D modeling in musculoskeletal reconstructions. The tail of this basal macronarian is relatively short compared to diplodocids and other coexisting macronarians. The center of mass lies well in front of the hindlimbs, which support only ca. half the body weight. Still, our reconstruction suggests a total weight for the entire tail of ca. 2500 kg. We conclude that the hypaxial and tail-related hindlimb muscles (most specifically the M. caudofemoralis longus and its counterpart the M. ilioischiocaudalis) in Giraffatitan were well developed and robustly built, compensating for the shorter length of the M. caufodemoralis longus, the main hindlimb retractor muscle, in comparison with other sauropods. Our methodology allows a better-constrained reconstruction of muscle volumes and masses in extinct taxa, and thus force and weight distributions throughout the tail, than non-volumetric approaches.
Incidence, Therapy, and Bleeding Risk—Cancer- Associated Thrombosis in Patients with Glioblastoma
Authors: Muster Viktoria , Gary Thomas
Published: May 2020

Cancer is an independent risk factor for the development of venous thromboembolism (VTE). Glioblastomas are amongst cancer types with the most thrombogenic potential and patients are at a particularly high risk of VTE with an incidence up to 20–30% per year. Currently, major efforts are underway to gain novel insights into risk factors and pathomechanisms to provide a better understanding of development of VTE in patients with primary brain tumors. Treatment of VTE requires therapeutic anticoagulation, which accordingly to recently-published guidelines should be performed using low molecular weight heparin or, in case of low bleeding risk, using a direct oral anticoagulant. However, this can be very challenging due to an increased risk of intracranial hemorrhage in this patient group. Furthermore, limited data are available on the subgroup of patients with primary brain tumors.
A 30-Year Long-Term Experience in Appendix Neuroendocrine Neoplasms—Granting a Positive Outcome
Authors: Vinagre João , Pinheiro Jorge , Martinho Olga , Reis Rui Manuel , Preto John , Soares Paula , Lopes José Manuel
Published: May 2020

Neuroendocrine neoplasms (NENs) are the most common tumor of the appendix and have an excellent prognosis. Appendiceal tumors diagnosed between 1989 and 2019 were reviewed, and clinical data were collected from patient files. Part of the series was immuno-profiled for markers related to cell cycle proliferation and/or senescence-type, apoptotic, and metastatic potential. Appendix NENs were detected in 74 patients, with 0.47% of incidence per appendectomy. The median age of the patients was 21.5 years, with two age peaks of incidence at 17.0 and 55.2 years. The median tumors size was 5.8 mm, and most were smaller than 10 mm. Lymphovascular and perineural invasion, as well as necrosis, was associated with larger tumor size. G1 tumors composed 96.0% of the cohort. The presence of moderate/strong p16 and the absent/low Bcl-2 expression was frequently observed and associated with a smaller size. This study represents one of the largest cohorts and with a long follow-up. For tumors smaller than 10 mm appendicectomy was sufficient as a curative procedure, as revealed by the good outcome. This series presented a 100% disease-free survival. The indolent phenotype of appendix NENs is supported by the expression of markers that point towards a strong inhibition of cell replication and growth inhibition.
PARP Inhibitors in the Treatment of Early Breast Cancer: The Step Beyond?
Authors: Gonçalves Anthony , Bertucci Alexandre , Bertucci François
Published: May 2020

Exquisitely exploiting defects in homologous recombination process, poly(ADP-ribose) polymerase (PARP) inhibitors have recently emerged as a promising class of therapeutics in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer with germline breast cancer 1 (BRCA1) or breast cancer 2 (BRCA2) mutations (gBRCA1/2m). In this setting, PARP inhibitors, either as single agent or in combination with platinum-based chemotherapy, significantly increased progression-free survival, as compared to conventional chemotherapy. Accordingly, further therapeutic advances are expected at an earlier stage of the disease. In the neoadjuvant setting, veliparib failed to increase the pathological complete response rate when added to a carboplatin-based regimen, in unselected triple-negative breast cancer patients. Similarly, when administered before anthracycline-cyclophosphamide, the neoadjuvant olaparib-paclitaxel combination was not superior to carboplatin–paclitaxel, in patients with HER2-negative breast cancer and BRCA1/2 mutation, or homologous recombination defect. Yet, neoadjuvant talazoparib, administered as a single-agent in patients with HER2-negative breast cancer and germline BRCA1/2 mutation, achieved an impressive pathological complete response rate of nearly 50%. In the adjuvant setting, the results from the OlympiA phase III study, evaluating adjuvant olaparib in HER2-negative early breast cancer and germline BRCA1/2 mutations, are eagerly awaited. Ongoing trials should clarify whether PARP inhibitors might improve outcome when administered in the adjuvant or neoadjuvant setting in early breast cancer patients with BRCA1/2 mutation or homologous recombination defect.
Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized Medicine
Authors: Rahman Mohammad Alinoor , Nasrin Farhana , Bhattacharjee Sonali , Nandi Saikat
Published: May 2020

Alternative splicing promotes proteome diversity by using limited number of genes, a key control point of gene expression. Splicing is carried out by large macromolecular machineries, called spliceosome, composed of small RNAs and proteins. Alternative splicing is regulated by splicing regulatory cis-elements in RNA and trans-acting splicing factors that are often tightly regulated in a tissue-specific and developmental stage-specific manner. The biogenesis of ribonucleoprotein (RNP) complexes is strictly regulated to ensure that correct complements of RNA and proteins are coordinated in the right cell at the right time to support physiological functions. Any perturbations that impair formation of functional spliceosomes by disrupting the cis-elements, or by compromising RNA-binding or function of trans-factors can be deleterious to cells and result in pathological consequences. The recent discovery of oncogenic mutations in splicing factors, and growing evidence of the perturbed splicing in multiple types of cancer, underscores RNA processing defects as a critical driver of oncogenesis. These findings have resulted in a growing interest in targeting RNA splicing as a therapeutic approach for cancer treatment. This review summarizes our current understanding of splicing alterations in cancer, recent therapeutic efforts targeting splicing defects in cancer, and future potentials to develop novel cancer therapies.
Inhibition of ATM Increases the Radiosensitivity of Uveal Melanoma Cells to Photons and Protons
Authors: Hussain Rumana N. , Coupland Sarah E. , Khzouz Jakub , Kalirai Helen , Parsons Jason L.
Published: May 2020

Treatment of uveal melanoma (UM) is generally successful, with local primary tumour control being at 90%–95%. Localized radiotherapy in the form of plaque brachytherapy or proton beam radiotherapy is the most common treatment modality in the UK. However, the basic mechanisms of radiation response, DNA repair and tissue reactions in UM have not been well documented previously. We have investigated the comparative radiosensitivity of four UM cell lines in response to exogenous radiation sources (both X-rays and protons), and correlated this with DNA repair protein expression and repair efficiency. We observed a broad range of radiosensitivity of different UM cell lines to X-rays and protons, with increased radioresistance correlating with elevated protein expression of ataxia telangiectasia mutated (ATM), a protein kinase involved in the signaling and repair of DNA double strand breaks. The use of an ATM inhibitor in UM cell lines enhanced radiosensitivity following both X-ray and proton irradiation, particularly in cells that contained high levels of ATM protein which are otherwise comparatively radioresistant. In proton-irradiated compared with non-irradiated primary enucleated UM patient samples, there was no significant difference in ATM protein expression. Our study therefore suggests that ATM is a potential target for increasing the radiosensitivity of more resistant UM subgroups.
Cisplatin Protein Binding Partners and Their Relevance for Platinum Drug Sensitivity
Authors: Möltgen Sophie , Piumatti Eleonora , Massafra Giuseppe , Metzger Sabine , Jaehde Ulrich , Kalayda Ganna
Published: May 2020

Cisplatin is a widely used drug in the treatment of various solid tumors, such as ovarian cancer. However, while the acquired resistance significantly limits the success of therapy, some tumors, such as colorectal cancer, are intrinsically insensitive to cisplatin. Only a small amount of intracellular platinum binds to the target—genomic DNA. The fate of the remaining drug is largely obscure. This work aimed to identify the cytosolic protein binding partners of cisplatin in ovarian and colorectal cancer cells and to evaluate their relevance for cell sensitivity to cisplatin and oxaliplatin. Using the fluorescent cisplatin analog BODIPY-cisplatin, two-dimensional gel electrophoresis, and mass spectrometry, we identified the protein binding partners in A2780 and cisplatin-resistant A2780cis ovarian carcinoma, as well as in HCT-8 and oxaliplatin-resistant HCT-8ox colorectal cell lines. Vimentin, only identified in ovarian cancer cells; growth factor receptor-bound protein 2, only identified in colorectal cancer cells; and glutathione-S-transferase π, identified in all four cell lines, were further investigated. The effect of pharmacological inhibition and siRNA-mediated knockdown on cytotoxicity was studied to assess the relevance of these binding partners. The silencing of glutathione-S-transferase π significantly sensitized intrinsically resistant HCT-8 and HCT-8ox cells to cisplatin, suggesting a possible involvement of the protein in the resistance of colorectal cancer cells to the drug. The inhibition of vimentin with FiVe1 resulted in a significant sensitization of A2780 and A2780cis cells to cisplatin, revealing new possibilities for improving the chemosensitivity of ovarian cancer cells.
Kidney Organoids and Tubuloids
Authors: Yousef Yengej Fjodor A. , Jansen Jitske , Rookmaaker Maarten B. , Verhaar Marianne C. , Clevers Hans
Published: May 2020

In the past five years, pluripotent stem cell (PSC)-derived kidney organoids and adult stem or progenitor cell (ASC)-based kidney tubuloids have emerged as advanced in vitro models of kidney development, physiology, and disease. PSC-derived organoids mimic nephrogenesis. After differentiation towards the kidney precursor tissues ureteric bud and metanephric mesenchyme, their reciprocal interaction causes self-organization and patterning in vitro to generate nephron structures that resemble the fetal kidney. ASC tubuloids on the other hand recapitulate renewal and repair in the adult kidney tubule and give rise to long-term expandable and genetically stable cultures that consist of adult proximal tubule, loop of Henle, distal tubule, and collecting duct epithelium. Both organoid types hold great potential for: (1) studies of kidney physiology, (2) disease modeling, (3) high-throughput screening for drug efficacy and toxicity, and (4) regenerative medicine. Currently, organoids and tubuloids are successfully used to model hereditary, infectious, toxic, metabolic, and malignant kidney diseases and to screen for effective therapies. Furthermore, a tumor tubuloid biobank was established, which allows studies of pathogenic mutations and novel drug targets in a large group of patients. In this review, we discuss the nature of kidney organoids and tubuloids and their current and future applications in science and medicine.
Anti-Inflammatory Performance of Lactose-Modified Chitosan and Hyaluronic Acid Mixtures in an In Vitro Macrophage-Mediated Inflammation Osteoarthritis Model
Authors: Tarricone Elena , Mattiuzzo Elena , Belluzzi Elisa , Elia Rossella , Benetti Andrea , Venerando Rina , Vindigni Vincenzo , Ruggieri Pietro , Brun Paola
Published: May 2020

The development and progression of osteoarthritis (OA) is associated with macrophage-mediated inflammation that generates a broad spectrum of cytokines and reactive oxygen species (ROS). This study investigates the effects of mid-MW hyaluronic acid (HA) in combination with a lactose-modified chitosan (CTL), on pro-inflammatory molecules and metalloproteinases (MMPs) expression, using an in vitro model of macrophage-mediated inflammation. Methods. To assess chondrocyte response to HA and CTL in the presence of macrophage derived inflammatory mediators, cells were exposed to the conditioned medium (CM) of U937 activated monocytes and changes in cell viability, pro-inflammatory mediators and MMPs expression or ROS generation were analysed. Results. CTL induced changes in chondrocyte viability that are reduced by the presence of HA. The CM of activated U937 monocytes (macrophages) significantly increased gene expression of pro-inflammatory molecules and MMPs and intracellular ROS generation in human chondrocyte cultures. HA, CTL and their combinations counteracted the oxidative damage and restored gene transcription for IL-1β, TNF-α, Gal-1, MMP-3 and MMP-13 to near baseline values. Conclusions. This study suggests that HA-CTL mixture attenuated macrophage-induced inflammation, inhibited MMPs expression and exhibited anti-oxidative effects. This evidence provides an initial step toward the development of an early stage OA therapeutic treatment
Targeted Regulation of Nuclear Lamins by Ubiquitin and Ubiquitin-Like Modifiers
Authors: Blank Michael
Published: May 2020

Nuclear lamins (NLs) are essential components of the animal cell nucleus involved in the regulation of a plethora of molecular and cellular processes. These include the nuclear envelope assembly and stability, mechanotransduction and chromatin organization, transcription, DNA replication, damage repair, and genomic integrity maintenance. Mutations in NLs can lead to the development of a wide range of distinct disease phenotypes, laminopathies, consisting of cardiac, neuromuscular, metabolic and premature aging syndromes. In addition, alterations in the expression of nuclear lamins were associated with different types of neoplastic diseases. Despite the importance and critical roles that NLs play in the diverse cellular activities, we only recently started to uncover the complexity of regulatory mechanisms governing their expression, localization and functions. This integrative review summarizes and discusses the recent findings on the emerging roles of ubiquitin and ubiquitin-like modifiers (ULMs) in the regulation of NLs, highlighting the intriguing molecular associations and cross-talks occurring between NLs and these regulatory molecules under physiological conditions and in the disease states.
Endothelial TRPV1 as an Emerging Molecular Target to Promote Therapeutic Angiogenesis
Authors: Negri Sharon , Faris Pawan , Rosti Vittorio , Antognazza Maria Rosa , Lodola Francesco , Moccia Francesco
Published: May 2020

Therapeutic angiogenesis represents an emerging strategy to treat ischemic diseases by stimulating blood vessel growth to rescue local blood perfusion. Therefore, injured microvasculature may be repaired by stimulating resident endothelial cells or circulating endothelial colony forming cells (ECFCs) or by autologous cell-based therapy. Endothelial Ca2+ signals represent a crucial player in angiogenesis and vasculogenesis; indeed, several angiogenic stimuli induce neovessel formation through an increase in intracellular Ca2+ concentration. Several members of the Transient Receptor Potential (TRP) channel superfamily are expressed and mediate Ca2+-dependent functions in vascular endothelial cells and in ECFCs, the only known truly endothelial precursor. TRP Vanilloid 1 (TRPV1), a polymodal cation channel, is emerging as an important player in endothelial cell migration, proliferation, and tubulogenesis, through the integration of several chemical stimuli. Herein, we first summarize TRPV1 structure and gating mechanisms. Next, we illustrate the physiological roles of TRPV1 in vascular endothelium, focusing our attention on how endothelial TRPV1 promotes angiogenesis. In particular, we describe a recent strategy to stimulate TRPV1-mediated pro-angiogenic activity in ECFCs, in the presence of a photosensitive conjugated polymer. Taken together, these observations suggest that TRPV1 represents a useful target in the treatment of ischemic diseases.
Mitochondrial MicroRNAs in Aging and Neurodegenerative Diseases
Authors: John Albin , Kubosumi Aaron , Reddy P. Hemachandra
Published: May 2020

MicroRNAs (miRNAs) are important regulators of several biological processes, such as cell growth, cell proliferation, embryonic development, tissue differentiation, and apoptosis. Currently, over 2000 mammalian miRNAs have been reported to regulate these biological processes. A subset of microRNAs was found to be localized to human mitochondria (mitomiRs). Through years of research, over 400 mitomiRs have been shown to modulate the translational activity of the mitochondrial genome. While miRNAs have been studied for years, the function of mitomiRs and their role in neurodegenerative pathologies is not known. The purpose of our article is to highlight recent findings that relate mitomiRs to neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s. We also discuss the involvement of mitomiRs in regulating the mitochondrial genome in age-related neurodegenerative diseases.
Application of 1H and 13C NMR Fingerprinting as a Tool for the Authentication of Maltese Extra Virgin Olive Oil
Authors: Lia Frederick , Vella Benjamin , Zammit Mangion Marion , Farrugia Claude
Published: May 2020

The application of 1H and 13C nuclear magnetic resonance (NMR) in conjunction with chemometric methods was applied for the discrimination and authentication of Maltese extra virgin olive oils (EVOOs). A total of 65 extra virgin olive oil samples, consisting of 30 Maltese and 35 foreign samples, were collected and analysed over four harvest seasons between 2013 and 2016. A preliminary examination of 1H NMR spectra using unsupervised principle component analysis (PCA) models revealed no significant clustering reflecting the geographical origin. In comparison, PCA carried out on 13C NMR spectra revealed clustering approximating the geographical origin. The application of supervised methods, namely partial least squares discriminate analysis (PLS-DA) and artificial neural network (ANN), on 1H and 13C NMR spectra proved to be effective in discriminating Maltese and non-Maltese EVOO samples. The application of variable selection methods significantly increased the effectiveness of the different classification models. The application of 13C NMR was found to be more effective in the discrimination of Maltese EVOOs when compared to 1H NMR. Furthermore, results showed that different 1H NMR pulse methods can greatly affect the discrimination of EVOOs. In the case of 1H NMR, the Nuclear Overhauser Effect (NOESY) pulse sequence was more informative when compared to the zg30 pulse sequence, since the latter required extensive spectral manipulation for the models to reach a satisfactory level of discrimination.
Identification of Callose Synthases in Stinging Nettle and Analysis of Their Expression in Different Tissues
Authors: Guerriero Gea , Piasecki Emilie , Berni Roberto , Xu Xuan , Legay Sylvain , Hausman Jean-Francois
Published: May 2020

Callose is an important biopolymer of β-1,3-linked glucose units involved in different phases of plant development, reproduction and response to external stimuli. It is synthesized by glycosyltransferases (GTs) known as callose synthases (CalS) belonging to family 48 in the Carbohydrate-Active enZymes (CAZymes) database. These GTs are anchored to the plasma membrane via transmembrane domains. Several genes encoding CalS have been characterized in higher plants with 12 reported in the model organism Arabidopsis thaliana. Recently, the de novo transcriptome of a fibre-producing clone of stinging nettle (Urtica dioica L.) was published and here it is mined for CalS genes with the aim of identifying members differentially expressed in the core and cortical tissues of the stem. The goal is to understand whether specific CalS genes are associated with distinct developmental stages of the stem internodes (elongation, thickening). Nine genes, eight of which encoding full-length CalS, are identified in stinging nettle. The phylogenetic analysis with CalS proteins from other fibre crops, namely textile hemp and flax, reveals grouping into 6 clades. The expression profiles in nettle tissues (roots, leaves, stem internodes sampled at different heights) reveal differences that are most noteworthy in roots vs. leaves. Two CalS are differentially expressed in the internodes sampled at the top and middle of the stem. Implications of their role in nettle stem tissue development are discussed.
Fetal Middle Cerebral Artery Pulsatility Index in No-Risk Pregnancies: Effects of Auditory Stimulation and Pregnancy Order
Authors: Jeličić Ljiljana , Janković Svetlana , Sovilj Mirjana , Adamović Tatjana , Bogavac Ivana , Gavrilović Aleksandar , Subotić Miško
Published: May 2020

Pulsatility index (PI) values in a fetal middle cerebral artery (MCA) were compared in no-risk pregnancies to examine the differences related to auditory stimulation test and pregnancy order. The study included 196 women with no-risk pregnancies selected from the database of more than 1000 pregnant women divided into two groups. Group 1 consisted of 98 nulliparous women (C1 = 98) and Group 2 consisted of 98 parous women (C2 = 98). All pregnant women were of comparable age and fetal gestational age (GA) when MCA-PI values were recorded. Measurements of PI values in fetal MCA were obtained before and immediately after the application of fetal auditory stimulation test. The MCA-PI measuring was conducted in the period between the 36th and the 41st week of GA. The results showed that PI baseline values and PI values after defined auditory stimulation were significantly different when measured in nulliparous women compared to parous women (p = 0.001; p = 0.003, respectively), while no group differences were observed in relative PI value changes due to auditory stimulation. These findings suggest that hemodynamic changes in fetal MCA caused by defined auditory stimulation measured by PI value changes may be valuable in the assessment of fetal auditory perception functionality and its development.
Effects of Anesthesia Techniques on Outcomes after Hip Fracture Surgery in Elderly Patients: A Prospective, Randomized, Controlled Trial
Authors: Shin Seokyung , Kim Seung Hyun , Park Kwan Kyu , Kim Seon Ju , Bae Jae Chan , Choi Yong Seon
Published: May 2020

The superiority of distinct anesthesia methods for geriatric hip fracture surgery remains unclear. We evaluated high mobility group box-1 (HMGB1) and interleukin-6 (IL-6) with three different anesthesia methods in elderly patients undergoing hip fracture surgery. Routine blood test findings, postoperative morbidity, and mortality were assessed as secondary outcome. In total, 176 patients were randomized into desflurane (n = 60), propofol (n = 58), or spinal groups (n = 58) that received desflurane-based balanced anesthesia, propofol-based total intravenous anesthesia (TIVA), or spinal anesthesia, respectively. The spinal group required less intraoperative vasopressors (p < 0.001) and fluids (p = 0.006). No significant differences in HMGB1 (pgroup×time = 0.863) or IL-6 (pgroup×time = 0.575) levels were noted at baseline, postoperative day (POD) 1, or POD2. Hemoglobin, albumin, creatinine, total lymphocyte count, potassium, troponin T, and C-reactive protein were comparable among groups at all time-points. No significant differences in postoperative hospital stay, intensive care unit (ICU) stay, and ventilator use among groups were observed. Postoperative pulmonary, cardiac, and neurologic complications; and in-hospital, 30-day, and 90-day mortality were not significantly different among groups (p = 0.974). In conclusion, HMGB1 and IL-6, and all secondary outcomes, were not significantly different between desflurane anesthesia, propofol TIVA, and spinal anesthesia.
Robot-Assisted versus Laparoscopic Donor Nephrectomy: A Comparison of 250 Cases
Authors: Zeuschner Philip , Hennig Linda , Peters Robert , Saar Matthias , Linxweiler Johannes , Siemer Stefan , Magheli Ahmed , Kramer Jürgen , Liefeldt Lutz , Budde Klemens , Schlomm Thorsten , Stöckle Michael , Friedersdorff Frank
Published: May 2020

Living kidney donation is the best treatment for end-stage renal disease, however, the best surgical approach for minimally-invasive donor nephrectomy (DN) is still a matter of debate. This bi-centric study aimed to retrospectively compare perioperative outcomes and postoperative kidney function after 257 transperitoneal DNs including 52 robot-assisted (RDN) and 205 laparoscopic DNs (LDN). As primary outcomes, the intraoperative (operating time, warm ischemia time (WIT), major complications) and postoperative (length of stay, complications) results were compared. As secondary outcomes, postoperative kidney and graft function were analyzed including delayed graft function (DGF) rates, and the impact of the surgical approach was assessed. Overall, the type of minimally-invasive donor nephrectomy (RDN vs. LDN) did not affect primary outcomes, especially not operating time and WIT; and major complication and DGF rates were low in both groups. A history of smoking and preoperative kidney function, but not the surgical approach, were predictive for postoperative serum creatinine of the donor and recipient. To conclude, RDN and LDN have equivalent perioperative results in experienced centers. For this reason, not the surgical approach, but rather the graft- (preoperative kidney function) and patient-specific (history of smoking) aspects impacted postoperative kidney function.
Clinical Outcome of Edoxaban vs. Vitamin K Antagonists in Patients with Atrial Fibrillation and Diabetes Mellitus: Results from a Multicenter, Propensity-Matched, Real-World Cohort Study
Authors: Russo Vincenzo , Attena Emilio , Rago Anna , Melillo Enrico , Di Micco Pierpaolo , Papa Andrea Antonio , Napolitano Giovanni , D’Onofrio Antonio , Golino Paolo , Nigro Gerardo
Published: May 2020

Diabetes mellitus (DM) is a chronic metabolic disease which is independently associated with unfavorable clinical outcomes in patients with atrial fibrillation (AF). Few real-world data are available about the clinical performance of non-vitamin K oral anticoagulants (NOACs) among patients with atrial fibrillation and diabetes. The aim of our propensity score-matched cohort study was to compare the safety and effectiveness of Edoxaban versus well-controlled vitamin K antagonists (VKAs) therapy among this population. In this study, we considered patients with AF and diabetes on Edoxaban or VKAs therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MB) and thromboembolic events (a composite of ischemic stroke, transient ischemic attack, systemic embolism) was respectively considered primary safety and effectiveness outcome. We identified 557 AF patients with diabetes who received Edoxaban (n: 230) or VKAs (n: 327) treatment. After propensity score matching analysis, 135 Edoxaban and 135 VKA recipients with similar clinical characteristics were evaluated. The mean follow-up was 27 ± 3 months. The incidence rate of thromboembolic events (TE) was 3.0 per 100 person-years (1.11 in Edoxaban vs. 1.9 in the VKA group, hazard ratio (HR): 0.59; 95% confidence interval (CI), 0.14 to 2.52; p = 0.48). The incidence rate of major bleedings (MB) was 3.7 per 100 person-years (1.2 in Edoxaban vs. 2.7 in the VKA group, HR: 0.43; 95% CI: 0.10 to 1.40; p = 0.14). The incidence rate of intracranial hemorrhage was 0.35 per 100 person-years in Edoxaban vs. 0.74 in the VKA group (HR: 0.49; 95% CI: 0.05 to 5.54; p = 0.56). A positive net clinical benefit (NCB) of Edoxaban over VKAs was found (+1.39). Insulin therapy (HR: 1.76, p = 0.004) and glycated hemoglobin (HR: 1.17, p = 0.002) were found to be independent predictors of TE; moreover, the concomitant use of antiplatelet drugs (HR: 2.41, p = 0.001) was an independent predictor of MB. Conclusions: Our data support the hypothesis of the safety and efficacy of Edoxaban for use in patients with AF and diabetes, justified by a favorable NCB over VKAs.
Insights into the Multi-Dimensional Dynamic Landscape of Epithelial–Mesenchymal Plasticity through Inter-Disciplinary Approaches
Authors: Kumar Jolly Mohit , Celia-Terrassa Toni
Published: May 2020

Epithelial–mesenchymal transition (EMT), first described by Dr [...]
Rheumatoid Meningitis a Rare Extra-Articular Manifestation of Rheumatoid Arthritis: Report of 6 Cases and Literature Review
Authors: Trabelsi Mélanie , Romand Xavier , Gilson Mélanie , Vaillant Mathieu , Guerne Pierre-André , Hayem Gilles , Bertolini Ewa , Baillet Athan , Gaudin Philippe
Published: May 2020

Objectives. Central neurological manifestations of rheumatoid arthritis (RA) like rheumatoid meningitis (RM) are rare, little known and have a high rate of morbi-mortality. METHODS. We described six cases of RM that were directly related to RA activity after exhaustive assessment. RESULTS. They were mainly women, aged of 50 to 69. All were positive for anti-cyclic citrullinated peptide antibodies and half for rheumatoid factors. RA activity, duration, and treatments were heterogeneous including oral steroids, conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs. Symptoms were various, with acute or progressive beginning; main were: generalized or focal seizure (4/6), fever (3/6), headaches (3/6), and frontal syndrome (2/6). Imaging lesions were four leptomeningitis, one pachymeningitis, and one association of both. MRI usually showed hypersignal in various territories in T2-FLAIR (fluid attenuated inversion recovery) mode, and enhancement in T1-weighted mode after gadolinium injection. All patients had lumbar puncture that found sterile cerebrospinal fluid, no neoplasic cell, elevated cell count in 5/6 cases and elevated proteins concentration in 3/6 cases. Cerebral biopsy was possible for three patients, and definitively confirmed the diagnosis of aseptic lepto- or pachymenintis, excluding vasculitis and lymphoma. Different treatments were used like intravenous high dose steroids, immunoglobulins or biologic DMARDs, with variable clinical and imaging outcome: one death, one complete recovery, and four recoveries with sequelae. Conclusions. Clinical symptoms, imaging, lumbar puncture, and serological studies are often nonspecific, only histologic examination can confirm the diagnosis of RM. Any central neurological manifestation in RA patients, even in quiescent and ancient RA, should warn the physician.
The Influence of Vaginal Native Tissue Repair (VNTR) on Various Aspects of Quality of Life in Women with Symptomatic Pelvic Organ Prolapse—A Prospective Cohort Study
Authors: Rechberger Ewa , Skorupska Katarzyna , Rechberger Tomasz , Kołodyńska Aleksandra , Miotła Paweł , Kulik-Rechberger Beata , Wróbel Andrzej
Published: May 2020

Pelvic organ prolapse (POP) and the associated functional disorders are a major epidemiological problem that compromises the quality of life (QoL). The aim of this study was to assess the impact of lower urinary tract symptoms (LUTS) related to POP and vaginal native tissue repair (VNTR) on QoL. Two hundred patients with symptomatic POP were stratified into four groups according to the dominant storage phase function disorders: Urgency; stress urinary incontinence (SUI); mixed urinary incontinence (MUI), and without clinically significant symptoms from lower urinary tract (LUT). They underwent VNTR from January 2018 to February 2019. After 12 months, the QoL was assessed by the Prolapse Quality of Life (P-QoL) and visual analogue scale (VAS) questionnaires. The data were analyzed with Statistica package version 12.0 (StatSoft, Krakow, Poland), using the Kalmogorow–Smirnoff, Shapiro–Wilk W and the one-way analysis of variance with post hoc Tukey tests. The results of P-QoL showed significant improvement (p < 0.05) in all the study groups in most domains assessed before surgery and 12 months after surgery. Significant improvements in all the symptoms assessed by the VAS scale results were found in groups Urgency and MUI. The LUTS questionnaire revealed significant improvement in all voiding and post voiding symptoms in these groups. VNTR effectively eliminated LUTS and significantly improved the patients’ QoL associated with POP.
Respiratory Mitochondrial Efficiency and DNA Oxidation in Human Sperm after In Vitro Myo-Inositol Treatment
Authors: Governini Laura , Ponchia Rosetta , Artini Paolo Giovanni , Casarosa Elena , Marzi Ilaria , Capaldo Angela , Luddi Alice , Piomboni Paola
Published: May 2020

Semen samples are known to contain abnormal amounts of reactive oxygen species (ROS) and oxygen free radicals; therefore, the identification of antioxidant molecules able to counteract the oxidative damage caused by ROS is foresight. Indeed, improving semen quality in terms of motility and reduction in DNA damage, can significantly improve the fertilization potential of sperm in vitro. To this regard, myo-inositol, based on its antioxidant properties, has been reported to be effective in improving sperm quality and motility in oligoasthenozoospermic patients undergoing assisted reproduction techniques when used as a dietary supplementation. Moreover, in vitro treatment demonstrated a direct relationship between myo-inositol, mitochondrial membrane potential and sperm motility. This experimental study aimed to evaluate the effects of myo-inositol (Andrositol-lab) in vitro treatment on sperm motility, capacitation, mitochondrial oxidative phosphorylation and DNA damage. Our results demonstrate that myo-inositol induces a significant increase in sperm motility and in oxygen consumption, the main index of oxidative phosphorylation efficiency and ATP production, both in basal and in in vitro capacitated samples. Moreover, we provide evidence for a significant protective role of myo-inositol against oxidative damage to DNA, thus supporting the in vitro use of myo-inositol in assisted reproductive techniques. Even if further studies are needed to clarify the mechanisms underlying the antioxidant properties of myo-inositol, the present findings significantly extend our knowledge on human male fertility and pave the way to the definition of evidence-based guidelines, aiming to improve the in vitro procedure currently used in ART laboratory for sperm selection.
Current Challenges in Chronic Bronchial Infection in Patients with Chronic Obstructive Pulmonary Disease
Authors: Lopez-Campos José Luis , Miravitlles Marc , de la Rosa Carrillo David , Cantón Rafael , Soler-Cataluña Juan Jose , Martinez-Garcia Miguel Angel
Published: May 2020

Currently, chronic obstructive pulmonary disease (COPD) patients and their physicians face a number of significant clinical challenges, one of which is the high degree of uncertainty related to chronic bronchial infection (CBI). By reviewing the current literature, several challenges can be identified, which should be considered as goals for research. One of these is to establish the bases for identifying the biological and clinical implications of the presence of potentially pathogenic microorganisms in the airways that should be more clearly elucidated according to the COPD phenotype. Another urgent area of research is the role of long-term preventive antibiotics. Clinical trials need to be carried out with inhaled antibiotic therapy to help clarify the profile of those antibiotics. The role of inhaled corticosteroids in patients with COPD and CBI needs to be studied to instruct the clinical management of these patients. Finally, it should be explored and confirmed whether a suitable antimicrobial treatment during exacerbations may contribute to breaking the vicious circle of CBI in COPD. The present review addresses the current state of the art in these areas to provide evidence which will enable us to progressively plan better healthcare for these patients.
Novel Fredericamycin Variant Overproduced by a Streptomycin-Resistant Streptomyces albus subsp. chlorinus Strain
Authors: Rodríguez Estévez Marta , Myronovskyi Maksym , Rosenkränzer Birgit , Paululat Thomas , Petzke Lutz , Ristau Jeanette , Luzhetskyy Andriy
Published: May 2020

Streptomycetes are an important source of natural products potentially applicable in the pharmaceutical industry. Many of these drugs are secondary metabolites whose biosynthetic genes are very often poorly expressed under laboratory cultivation conditions. In many cases, antibiotic-resistant mutants exhibit increased production of natural drugs, which facilitates the identification and isolation of new substances. In this study, we report the induction of a type II polyketide synthase gene cluster in the marine strain Streptomyces albus subsp. chlorinus through the selection of streptomycin-resistant mutants, resulting in overproduction of the novel compound fredericamycin C2 (1). Fredericamycin C2 (1) is structurally related to the potent antitumor drug lead fredericamycin A.
Introducing Osteology: An International, Peer-Reviewed Open Access Journal to Foster Bone Science
Authors: Longo Umile Giuseppe
Published: May 2020

The fascinating field of osteology is rapidly developing [...]
RETRACTED: Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation
Authors: Fahmy Usama , Badr-Eldin Shaimaa , Ahmed Osama , Aldawsari Hibah , Tima Singkome , Asfour Hani , Al-Rabia Mohammed , Negm Aya , Sultan Muhammad , Madkhali Osama , Alhakamy Nabil
Published: May 2020

Flibanserin (FLB) is a multifunctional serotonergic agent that was recently approved by the FDA for the oral treatment of premenopausal women with hypoactive sexual desire disorder. FLB is a centrally acting drug that has a low oral bioavailability of 33% owing to its exposure to the hepatic first-pass effect, as well as its pH-dependent solubility, which could be an obstacle hindering the drug dissolution and absorption via mucosal barriers. Thus, this work aimed at overcoming the aforementioned drawbacks and promoting the nose-to-brain delivery of FLB via the formulation of an intra-nasal in situ niosomal gel. The Box–Behnken design was employed to study the impact of Span® 85 concentration (X1), hydration time (X2), and pH of the hydrating buffer (X3) on the vesicle size and drug entrapment. The optimized formulation exhibited a spherical shape with a vesicular size of 46.35 nm and entrapment efficiency of 92.48%. The optimized FLB niosomes integrated into gellan gum-based in situ gel exhibited enhanced ex vivo permeation and improved plasma and brain concentrations after nasal administration in rats compared to raw FLB. These findings highlight the capability of the proposed intra-nasal FLB niosomal in situ gel to boost the drug bioavailability and to promote its direct delivery to the brain.
Biocompatibility and Antimicrobial Activity of Reynoutria elliptica Extract for Dental Application
Authors: Yang Song-Yi , Kang Min-Kyung
Published: May 2020

This study was conducted to determine whether nature-derived Reynoutria elliptica extracts exhibit biocompatibility and antimicrobial effects against oral pathogens such as Streptococcus mutans and Candida albicans. Fine particles of Reynoutria elliptica extract were used to probe for biocompatibility and antimicrobial activity toward these pathogens, and results were evaluated with an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, spectrophotometric growth inhibitory assay, the total number of colony-forming units (CFU), an agar disk diffusion test, and scanning electron microscopy (SEM). In addition, UV/VIS spectroscopy was used to determine the levels of flavonoid and polyphenol in experimental solutions. Several experimental groups showed cell viability higher than 70%, and the antimicrobial activity toward both S. mutans and C. albicans was significantly higher than was that seen for the control group. In CFU and agar disk diffusion tests with C. albicans, increases in the concentration of Reynoutria elliptica extract led to significantly increased antimicrobial effects. Additionally, SEM results showed that Reynoutria elliptica extract changed the morphology and density of S. mutans and C. albicans. The results of this research can be applied to the use of Reynoutria elliptica extracts for the development of oral products that are biologically friendly and can control oral diseases such as dental caries and candida-associated denture stomatitis.
Effects of pH and Mineral Nutrition on Growth and Physiological Responses of Trembling Aspen (Populus tremuloides), Jack Pine (Pinus banksiana), and White Spruce (Picea glauca) Seedlings in Sand Culture
Authors: Xu Feng , Vaziriyeganeh Maryamsadat , Zwiazek Janusz J.
Published: May 2020

Responses of trembling aspen (Populus tremuloides), jack pine (Pinus banksiana), and white spruce (Picea glauca) seedlings to root zone pH ranging from 5 to 9 were studied in sand culture in the presence of two mineral nutrition levels. After eight weeks of treatments, effects of pH on plant dry weights varied between the plant species and were relatively minor in white spruce. Higher nutrient supply significantly increased dry weights only in trembling aspen subjected to pH 5 treatment. There was little effect of pH and nutrition level on net photosynthesis and transpiration rates in white spruce and jack pine, but net photosynthesis markedly declined in aspen at high pH. Chlorophyll concentrations in young foliage decreased the most in trembling aspen and jack pine. The effects of high pH treatments on the concentrations of Mg, P, Ca, Mn, Zn, and Fe in young foliage varied between the plant species with no significant decreases of Fe and Zn recorded in trembling aspen and white spruce, respectively. This was in contrast to earlier reports from the studies carried out in hydroponic culture. The sand culture system that we developed could be a more suitable alternative to hydroponics to study plant responses to pH in the root zone. Plant responses to high pH appear to involve complex events with a likely contribution of nutritional effects and altered water transport processes.