bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteins Do Not Replicate, They Precipitate: Phase Transition and Loss of Function Toxicity in Amyloid Pathologies
Authors: Ezzat Kariem , Sturchio Andrea , Espay Alberto J.
Published: March 2022

Protein aggregation into amyloid fibrils affects many proteins in a variety of diseases, including neurodegenerative disorders, diabetes, and cancer. Physicochemically, amyloid formation is a phase transition process, where soluble proteins are transformed into solid fibrils with the characteristic cross-β conformation responsible for their fibrillar morphology. This phase transition proceeds via an initial, rate-limiting nucleation step followed by rapid growth. Several well-defined nucleation pathways exist, including homogenous nucleation (HON), which proceeds spontaneously; heterogeneous nucleation (HEN), which is catalyzed by surfaces; and seeding via preformed nuclei. It has been hypothesized that amyloid aggregation represents a protein-only (nucleic-acid free) replication mechanism that involves transmission of structural information via conformational templating (the prion hypothesis). While the prion hypothesis still lacks mechanistic support, it is also incompatible with the fact that proteins can be induced to form amyloids in the absence of a proteinaceous species acting as a conformational template as in the case of HEN, which can be induced by lipid membranes (including viral envelopes) or polysaccharides. Additionally, while amyloids can be formed from any protein sequence and via different nucleation pathways, they invariably adopt the universal cross-β conformation; suggesting that such conformational change is a spontaneous folding event that is thermodynamically favorable under the conditions of supersaturation and phase transition and not a templated replication process. Finally, as the high stability of amyloids renders them relatively inert, toxicity in some amyloid pathologies might be more dependent on the loss of function from protein sequestration in the amyloid state rather than direct toxicity from the amyloid plaques themselves.
DNA-Binding Properties of a Novel Crenarchaeal Chromatin-Organizing Protein in Sulfolobus acidocaldarius
Authors: Lemmens Liesbeth , Wang Kun , Ruykens Ebert , Nguyen Van Tinh , Lindås Ann-Christin , Willaert Ronnie , Couturier Mohea , Peeters Eveline
Published: March 2022

In archaeal microorganisms, the compaction and organization of the chromosome into a dynamic but condensed structure is mediated by diverse chromatin-organizing proteins in a lineage-specific manner. While many archaea employ eukaryotic-type histones for nucleoid organization, this is not the case for the crenarchaeal model species Sulfolobus acidocaldarius and related species in Sulfolobales, in which the organization appears to be mostly reliant on the action of small basic DNA-binding proteins. There is still a lack of a full understanding of the involved proteins and their functioning. Here, a combination of in vitro and in vivo methodologies is used to study the DNA-binding properties of Sul12a, an uncharacterized small basic protein conserved in several Sulfolobales species displaying a winged helix–turn–helix structural motif and annotated as a transcription factor. Genome-wide chromatin immunoprecipitation and target-specific electrophoretic mobility shift assays demonstrate that Sul12a of S. acidocaldarius interacts with DNA in a non-sequence specific manner, while atomic force microscopy imaging of Sul12a–DNA complexes indicate that the protein induces structural effects on the DNA template. Based on these results, and a contrario to its initial annotation, it can be concluded that Sul12a is a novel chromatin-organizing protein.
Oxidative Stress- and Autophagy-Inducing Effects of PSI-LHCI from Botryococcus braunii in Breast Cancer Cells
Authors: Joaquín-Ovalle Freisa , Guihurt Grace , Barcelo-Bovea Vanessa , Hani-Saba Andraous , Fontanet-Gómez Nicole , Ramirez-Paz Josell , Kashino Yasuhiro , Torres-Martinez Zally , Doble-Cacho Katerina , Delinois Louis , Delgado Yamixa , Griebenow Kai
Published: March 2022

Botryococcus braunii (B. braunii) is a green microalga primarily found in freshwater, reservoirs, and ponds. Photosynthetic pigments from algae have shown many bioactive molecules with therapeutic potential. Herein, we report the purification, characterization, and anticancer properties of photosystem I light-harvesting complex I (PSI-LHCI) from the green microalga B. braunii UTEX2441. The pigment–protein complex was purified by sucrose density gradient and characterized by its distinctive peaks using absorption, low-temperature (77 K) fluorescence, and circular dichroism (CD) spectroscopic analyses. Protein complexes were resolved by blue native-PAGE and two-dimensional SDS-PAGE. Triple-negative breast cancer MDA-MB-231 cells were incubated with PSI-LHCI for all of our experiments. Cell viability was assessed, revealing a significant reduction in a time- and concentration-dependent manner. We confirmed the internalization of PSI-LHCI within the cytoplasm and nucleus after 12 h of incubation. Cell death mechanism by oxidative stress was confirmed by the production of reactive oxygen species (ROS) and specifically superoxide. Furthermore, we monitored autophagic flux, apoptotic and necrotic features after treatment with PSI-LHCI. Treated MDA-MB-231 cells showed positive autophagy signals in the cytoplasm and nucleus, and necrotic morphology by the permeabilization of the cell membrane. Our findings demonstrated for the first time the cytotoxic properties of B. braunii PSI-LHCI by the induction of ROS and autophagy in breast cancer cells.
Intratumoral Immunotherapy and Tumor Ablation: A Local Approach with Broad Potential
Authors: Senders Zachary J. , Martin Robert C. G.
Published: March 2022

Several intratumoral immunotherapeutic agents have shown efficacy in controlling local disease; however, their ability to induce a durable systemic immune response is limited. Likewise, tumor ablation is well-established due to its role in local disease control but generally produces only a modest immunogenic effect. It has recently been recognized, however, that there is potential synergy between these two modalities and their distinct mechanisms of immune modulation. The aim of this review is to evaluate the existing data regarding multimodality therapy with intratumoral immunotherapy and tumor ablation. We discuss the rationale for this therapeutic approach, highlight novel combinations, and address the challenges to their clinical utility. There is substantial evidence that combination therapy with intratumoral immunotherapy and tumor ablation can potentiate durable systemic immune responses and should be further evaluated in the clinical setting.
Associations between Pre-Diagnostic Physical Activity with Breast Cancer Characteristics and Survival
Authors: Lim Zi Lin , Lim Geok Hoon , Ho Peh Joo , Khng Alexis Jiaying , Yeoh Yen Shing , Ong Amanda Tse Woon , Tan Benita Kiat Tee , Tan Ern Yu , Tan Su-Ming , Tan Veronique Kiak-Mien , Li Jingmei , Hartman Mikael
Published: March 2022

Physical activity (PA) is known to reduce breast cancer (BC) risk and improve patient prognosis. However, the association between pre-diagnostic PA and the aggressiveness of BC is unclear. We investigated the associations between PA, BC tumour characteristics, and survival. This retrospective observational study included 7688 BC patients from the Singapore Breast Cancer Cohort (2010–2016). PA information from the questionnaire included intensity (light/moderate/vigorous) and duration (<1 h/1–2 h/>2 h per week). A PA score (1–5) incorporating intensity and duration was calculated. Associations between PA score and tumour characteristics such as stage, histological grade, nodal and hormone receptor status were examined using multinomial regression. Moreover, 10-year overall survival was estimated using Cox regression analysis in 6572 patients after excluding patients with invalid survival data and stage IV disease. Breast tumours associated with higher PA score were more likely to be non-invasive (ORinvasive vs. non-invasive(reference) [95% CI]: 0.71 [0.58–0.87], p-trend = 0.001), of lower grade (ORpoorly vs. well differentiated(reference): 0.69 [0.52–0.93], p = 0.014), ER-positive (ORER-negative vs. ER-positive(reference): 0.94 [0.89–1.00], p-trend = 0.049), PR-positive (ORPR-negative vs. PR-positive(reference): 0.82 [0.67–0.99], p = 0.041), HER2-negative (ORHER2-negative vs. HER2-positive(reference): 1.29 [1.02–1.62], p-trend = 0.002), and less likely to be of HER2-overexpressed subtype (ORHER2-overexpressed vs. Luminal A(reference): 0.89 [0.81–0.98], p-trend = 0.018). These associations (odds ratios) were more pronounced among post-menopausal patients. A higher PA score did not improve survival. Higher levels of pre-diagnostic PA were associated with less aggressive tumours in BC patients. This illustrated another benefit of PA in addition to its known role in BC risk reduction.
Lung Adenocarcinoma Tumor Origin: A Guide for Personalized Medicine
Authors: Seguin Laetitia , Durandy Manon , Feral Chloe C.
Published: March 2022

Lung adenocarcinoma, the major form of lung cancer, is the deadliest cancer worldwide, due to its late diagnosis and its high heterogeneity. Indeed, lung adenocarcinoma exhibits pronounced inter- and intra-tumor heterogeneity cofounding precision medicine. Tumor heterogeneity is a clinical challenge driving tumor progression and drug resistance. Several key pieces of evidence demonstrated that lung adenocarcinoma results from the transformation of progenitor cells that accumulate genetic abnormalities. Thus, a better understanding of the cell of origin of lung adenocarcinoma represents an opportunity to unveil new therapeutic alternatives and stratify patient tumors. While the lung is remarkably quiescent during homeostasis, it presents an extensive ability to respond to injury and regenerate lost or damaged cells. As the lung is constantly exposed to potential insult, its regenerative potential is assured by several stem and progenitor cells. These can be induced to proliferate in response to injury as well as differentiate into multiple cell types. A better understanding of how genetic alterations and perturbed microenvironments impact progenitor-mediated tumorigenesis and treatment response is of the utmost importance to develop new therapeutic opportunities.
MALDI Mass Spectrometry Imaging—Prognostic Pathways and Metabolites for Renal Cell Carcinomas
Authors: Erlmeier Franziska , Sun Na , Shen Jian , Feuchtinger Annette , Buck Achim , Prade Verena M. , Kunzke Thomas , Schraml Peter , Moch Holger , Autenrieth Michael , Weichert Wilko , Hartmann Arndt , Walch Axel
Published: March 2022

High mass resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is a suitable method for biomarker detection for several tumor entities. Renal cell carcinoma (RCC) is the seventh most common cancer type and accounts for more than 80% of all renal tumors. Prognostic biomarkers for RCC are still missing. Therefore, we analyzed a large, multicenter cohort including the three most common RCC subtypes (clear cell RCC (ccRCC), papillary RCC (pRCC) and chromophobe RCC (chRCC)) by MALDI for prognostic biomarker detection. MALDI-Fourier-transform ion cyclotron resonance (FT-ICR)-MSI analysis was performed for renal carcinoma tissue sections from 782 patients. SPACiAL pipeline was integrated for automated co-registration of histological and molecular features. Kaplan–Meier analyses with overall survival as endpoint were executed to determine the metabolic features associated with clinical outcome. We detected several pathways and metabolites with prognostic power for RCC in general and also for different RCC subtypes.
The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer
Authors: Otake Sotaro , Goto Taichiro , Higuchi Rumi , Nakagomi Takahiro , Hirotsu Yosuke , Amemiya Kenji , Oyama Toshio , Mochizuki Hitoshi , Omata Masao
Published: March 2022

Although bronchoscopy is generally performed to diagnose lung cancer, its diagnostic yield remains unsatisfactory. Assuming that lung cancer cells release cell-free DNA into the epithelial lining fluid, we hypothesized that lung cancer could be diagnosed by analyzing gene mutations in cell-free DNA in this fluid. This study included 32 patients with lung cancer who underwent surgery at our hospital. Bronchoalveolar lavage (BAL) was performed on the resected lung samples (ex vivo BAL model) after lobectomy. Each DNA sample (i.e., BAL fluid, primary lesion, and plasma) underwent deep targeted sequencing. Gene mutation analyses in the BAL fluid samples identified mutations identical to those in the primary lesions in 30 (93.8%) of 32 patients. In contrast, the microscopic cytology of the same BAL fluid samples yielded a diagnosis of lung cancer in only one of 32 patients, and the analysis of plasma samples revealed gene mutations identical to those in the primary lesions in only one of 32 patients. In conclusion, cell-free DNA released from lung cancer cells exists more abundantly in the airway than in the blood. The collection and analysis of the BAL fluid containing cell-free DNA derived from lung cancer can thus allow lung cancer diagnosis and the screening of driver mutations.
Iron Carbon Catalyst Initiated the Generation of Active Free Radicals without Oxidants for Decontamination of Methylene Blue from Waters
Authors: Liu Yan , Xie Guangyu , Li Guoyu , Cui Jingye , Li Chuang , Xu Hao , Lu Yating , Jin Qi , Zhou Daixi , Hu Xinjiang
Published: March 2022

In conventional oxidation technologies for treatment of contaminated waters, secondary pollution of the aqueous environment often occurs because of the additional oxidants generated during the process. To avoid this problem, Fe/NG catalyst composites without additives were developed in this study for decontamination of methylene blue (MB) from waters. The Fe/NG catalyst, composed of carbon nitride and iron chloride (FeCl3·6H2O), was prepared by high temperature pyrolysis. It is an exceptionally efficient, recoverable, and sustainable catalyst for degradation of organic matter. The morphological characteristics, chemical structure, and surface properties of the catalyst composites were investigated. The catalyst exhibited high MB removal efficiency (100%) within 30 min under ambient temperature and dark conditions. The experiments indicated that an MB degradation effect was also applicable under most acid–base conditions (pH = 2–10). The characterization results using electron spin resonance and analysis of intermediate products demonstrated that free radicals such as ·OH and ·O2− were produced from the Fe/NG composites in the heterogeneous system, which resulted in the high MB degradation efficiency. Moreover, the catalysis reaction generated reducing substances, triggering iron carbon micro-electrolysis to spontaneously develop a microcurrent, which assisted the degradation of MB. This study demonstrates the feasibility of Fe/NG catalysts that spontaneously generate active species for degrading pollutants in an aqueous environment at normal temperature, providing an attractive approach for treating organic-contaminated waters.
Mitochondrial Respiratory Complexes as Targets of Drugs: The PPAR Agonist Example
Authors: Bottoni Patrizia , Pontoglio Alessandro , Scarà Salvatore , Pieroni Luisa , Urbani Andrea , Scatena Roberto
Published: March 2022

Mitochondrial bioenergetics are progressively acquiring significant pathophysiological roles. Specifically, mitochondria in general and Electron Respiratory Chain in particular are gaining importance as unintentional targets of different drugs. The so-called PPAR ligands are a class of drugs which not only link and activate Peroxisome Proliferator-Activated Receptors but also show a myriad of extrareceptorial activities as well. In particular, they were shown to inhibit NADH coenzyme Q reductase. However, the molecular picture of this intriguing bioenergetic derangement has not yet been well defined. Using high resolution respirometry, both in permeabilized and intact HepG2 cells, and a proteomic approach, the mitochondrial bioenergetic damage induced by various PPAR ligands was evaluated. Results show a derangement of mitochondrial oxidative metabolism more complex than one related to a simple perturbation of complex I. In fact, a partial inhibition of mitochondrial NADH oxidation seems to be associated not only with hampered ATP synthesis but also with a significant reduction in respiratory control ratio, spare respiratory capacity, coupling efficiency and, last but not least, serious oxidative stress and structural damage to mitochondria.
Multi-Omics Approach Reveals Dysregulation of Protein Phosphorylation Correlated with Lipid Metabolism in Mouse Non-Alcoholic Fatty Liver
Authors: Kim Sora Q. , Mohallem Rodrigo , Franco Jackeline , Buhman Kimberly K. , Kim Kee-Hong , Aryal Uma K.
Published: March 2022

Obesity caused by overnutrition is a major risk factor for non-alcoholic fatty liver disease (NAFLD). Several lipid intermediates such as fatty acids, glycerophospholipids and sphingolipids are implicated in NAFLD, but detailed characterization of lipids and their functional links to proteome and phosphoproteome remain to be elucidated. To characterize this complex molecular relationship, we used a multi-omics approach by conducting comparative proteomic, phoshoproteomic and lipidomic analyses of high fat (HFD) and low fat (LFD) diet fed mice livers. We quantified 2447 proteins and 1339 phosphoproteins containing 1650 class I phosphosites, of which 669 phosphosites were significantly different between HFD and LFD mice livers. We detected alterations of proteins associated with cellular metabolic processes such as small molecule catabolic process, monocarboxylic acid, long- and medium-chain fatty acid, and ketone body metabolic processes, and peroxisome organization. We observed a significant downregulation of protein phosphorylation in HFD fed mice liver in general. Untargeted lipidomics identified upregulation of triacylglycerols, glycerolipids and ether glycerophosphocholines and downregulation of glycerophospholipids, such as lysoglycerophospholipids, as well as ceramides and acylcarnitines. Analysis of differentially regulated phosphosites revealed phosphorylation dependent deregulation of insulin signaling as well as lipogenic and lipolytic pathways during HFD induced obesity. Thus, this study reveals a molecular connection between decreased protein phosphorylation and lipolysis, as well as lipid-mediated signaling in diet-induced obesity.
Third-Line Antiretroviral Therapy: What Do We Do When the Appropriate Formulations Are Not Available?
Authors: Frigati Lisa Jane , Rabie Helena
Published: March 2022

Children on antiretroviral therapy have limited options, particularly if they are failing therapy and live in resource-poor settings. We describe three cases where children accessed third-line antiretroviral therapy off-label, or used them extemporaneously with successful outcomes. We then review the evidence for performing this measure. There is an urgent need for appropriate formulations to treat young children who require a third-line or salvage regimen.
Forensic Analysis of COVID-19 Data from 198 Countries Two Years after the Pandemic Outbreak
Authors: Farhadi Noah , Lahooti Hooshang
Published: March 2022

The availability of accurate information has proved fundamental to managing health crises. This research examined pandemic data provided by 198 countries worldwide two years after the outbreak of the deadly Coronavirus in Wuhan, China. We compiled and reevaluated the consistency of daily COVID-19 infections with Benford’s Law. It is commonly accepted that the distribution of the leading digits of pandemic data should conform to Newcomb-Benford’s expected frequencies. Consistency with the law of leading digits might be an indicator of data reliability. Our analysis shows that most countries have disseminated partially reliable data over 24 months. The United States, Israel, and Spain spread the most consistent COVID-19 data with the law. In line with previous findings, Belarus, Iraq, Iran, Russia, Pakistan, and Chile published questionable epidemic data. Against this trend, 45 percent of countries worldwide appeared to demonstrate significant BL conformity. Our measures of Benfordness were moderately correlated with the Johns Hopkins Global Health Security Index, suggesting that the conformity to Benford’s law may also depend on national health care policies and practices. Our findings might be of particular importance to policymakers and researchers around the world.
Utilizing Ecological Modeling to Follow the Potential Spread of Honey Bee Pest (Megaselia scalaris) from Nearby Countries towards Saudi Arabia under Climate Change Conditions
Authors: Alkhalaf Areej A.
Published: March 2022

The current challenge for the development of beekeeping is the possibility of bee pests invading new areas. It is well known that each geographical range has its unique pest species. The fly Megaselia scalaris is a facultative parasitoid to honey bees. This fly has been recorded in various countries while information about it in Saudi Arabia is still seldom. The main objective of this study was to follow the spread of this fly from North Africa/South Europe towards Gulf countries utilizing ecological modeling. Maxent, as a specialist software in analyzing species distribution, was used in combination of five environmental factors. The analysis was performed to cover current and future conditions (2050). The outputs of the model were analyzed in regard to their performance and distribution of M. scalaris in the study area. The top factor contributing to the model was the annual mean temperature with a percentage of 56.3. The model maps emphasized the possible occurrence of this pest in the northern parts of Saudi Arabia. The wide establishment and distribution towards the central and southern parts of Saudi Arabia were not supported. Screening apiaries located in Northern areas in Saudi Arabia for the presence of this pest using specific bait traps could be a good recommendation from this study.
Neuroimaging Findings in a Patient with Anti-IgLON5 Disease: Cerebrospinal Fluid Dynamics Abnormalities
Authors: Urso Daniele , De Blasi Roberto , Anastasia Antonio , Gnoni Valentina , Rizzo Valentina , Nigro Salvatore , Tafuri Benedetta , Iacolucci Carlo Maria , Zecca Chiara , Dell’Abate Maria Teresa , Andreetta Francesca , Logroscino Giancarlo
Published: March 2022

Anti-IgLON5 disease is a recently described autoimmune neurodegenerative disorder characterized by insidious onset, slow progression and a variety of neurological features. Neuroimaging in most patients with anti-IgLON5 disease is normal or shows nonspecific findings. Here, we report a case of anti-IgLON5 disease presenting with parkinsonism, falls, sleep problems with severe nocturnal dyspnea attacks, dysphagia, and dysautonomia. Imaging findings were initially suggestive of progressive supranuclear palsy. An altered cerebrospinal fluid dynamic was found on an MRI as well as high-convexity hyperperfusion on a brain SPECT. Further case descriptions with neuroimaging are required to characterize cerebral and cerebrospinal fluid dynamics abnormalities in this rare condition.
First-in-Human Study of [68Ga]Ga-NODAGA-E[c(RGDyK)]2 PET for Integrin αvβ3 Imaging in Patients with Breast Cancer and Neuroendocrine Neoplasms: Safety, Dosimetry and Tumor Imaging Ability
Authors: Clausen Malene Martini , Carlsen Esben Andreas , Christensen Camilla , Madsen Jacob , Brandt-Larsen Malene , Klausen Thomas Levin , Holm Søren , Loft Annika , Berthelsen Anne Kiil , Kroman Niels , Knigge Ulrich , Kjaer Andreas
Published: March 2022

Arginine-Glycine-Aspartate (RGD)-recognizing cell surface integrins are involved in tumor growth, invasiveness/metastases, and angiogenesis, and are therefore an attractive treatment target in cancers. The subtype integrin αvβ3 is upregulated on endothelial cells during angiogenesis and on tumor cells. In vivo assessment of integrin αvβ3 is possible with positron emission tomography (PET). Preclinical data on radiochemical properties, tumor uptake and radiation exposure identified [68Ga]Ga-NODAGA-E[c(RGDyK)]2 as a promising candidate for clinical translation. In this first-in-human phase I study, we evaluate [68Ga]Ga-NODAGA-E[c(RGDyK)]2 PET in patients with neuroendocrine neoplasms (NEN) and breast cancer (BC). The aim was to investigate safety, biodistribution and dosimetry as well as tracer uptake in tumor lesions. A total of 10 patients (5 breast cancer, 5 neuroendocrine neoplasm) received a single intravenous dose of approximately 200 MBq [68Ga]Ga-NODAGA-E[c(RGDyK)]2. Biodistribution profile and dosimetry were assessed by whole-body PET/CT performed at 10 min, 1 h and 2 h after injection. Safety assessment with vital parameters, electrocardiograms and blood tests were performed before and after injection. In vivo stability of [68Ga]Ga-NODAGA-E[c(RGDyK)]2 was determined by analysis of blood and urine. PET images were analyzed for tracer uptake in tumors and background organs. No adverse events or pharmacologic effects were observed in the 10 patients. [68Ga]Ga-NODAGA-E[c(RGDyK)]2 exhibited good in vivo stability and fast clearance, primarily by renal excretion. The effective dose was 0.022 mSv/MBq, equaling a radiation exposure of 4.4 mSv at an injected activity of 200 MBq. The tracer demonstrated stable tumor retention and good image contrast. In conclusion, this first-in-human phase I trial demonstrated safe use of [68Ga]Ga-NODAGA-E[c(RGDyK)]2 for integrin αvβ3 imaging in cancer patients, low radiation exposure and favorable uptake in tumors. Further studies are warranted to establish whether [68Ga]Ga-NODAGA-E[c(RGDyK)]2 may become a tool for early identification of patients eligible for treatments targeting integrin αvβ3 and for risk stratification of patients.
DigiPatICS: Digital Pathology Transformation of the Catalan Health Institute Network of 8 Hospitals—Planification, Implementation, and Preliminary Results
Authors: Temprana-Salvador Jordi , López-García Pablo , Castellví Vives Josep , de Haro Lluís , Ballesta Eudald , Rojas Abusleme Matias , Arrufat Miquel , Marques Ferran , Casas Josep R. , Gallego Carlos , Pons Laura , Mate José Luis , Fernández Pedro Luis , López-Bonet Eugeni , Bosch Ramon , Martínez Salomé , Ramón y Cajal Santiago , Matias-Guiu Xavier
Published: March 2022

Complete digital pathology transformation for primary histopathological diagnosis is a challenging yet rewarding endeavor. Its advantages are clear with more efficient workflows, but there are many technical and functional difficulties to be faced. The Catalan Health Institute (ICS) has started its DigiPatICS project, aiming to deploy digital pathology in an integrative, holistic, and comprehensive way within a network of 8 hospitals, over 168 pathologists, and over 1 million slides each year. We describe the bidding process and the careful planning that was required, followed by swift implementation in stages. The purpose of the DigiPatICS project is to increase patient safety and quality of care, improving diagnosis and the efficiency of processes in the pathological anatomy departments of the ICS through process improvement, digital pathology, and artificial intelligence tools.
Blood Plasma Exosomes Contain Circulating DNA in Their Crown
Authors: Tutanov Oleg , Shtam Tatiana , Grigor’eva Alina , Tupikin Alexey , Tsentalovich Yuri , Tamkovich Svetlana
Published: March 2022

It is known that circulating DNA (cirDNA) is protected from nuclease activity by proteins that form macromolecular complexes with DNA. In addition, it was previously shown that cirDNA can bind to the outer surface of exosomes. NTA analysis and real-time PCR show that exosomes from healthy females (HF) or breast cancer patients (BCP) plasma contain less than 1.4 × 10−8 pg of DNA. Thus, only a minor part of cirDNA is attached to the outer side of the exosome as part of the vesicle crown: the share of exosomal DNA does not exceed 0.025% HF plasma DNA and 0.004% BCP plasma DNA. Treatment of plasma exosomes with DNase I with subsequent dot immunoassay reveals that H2a, H2b, and H3 histones are not part of the exosomal membrane, but are part of the cirDNA–protein macromolecular complex associated with the surface of the exosome either through interaction with DNA-binding proteins or with histone-binding proteins. Using bioinformatics approaches after identification by MALDI-TOF mass spectrometry, 16 exosomal DNA-binding proteins were identified. It was shown that four proteins—AIFM1, IGHM, CHD5, and KCNIP3—are candidates for DNA binding on the outer membrane of exosomes; the crown of exosomes may include five DNA-binding proteins: H2a, H2b, H3, IGHM, and ALB. Of note, AIFM1, IGHM, and CHD5 proteins are found only in HF plasma exosomes; KCNIP3 protein is identified only in BCP plasma exosomes; and H2a, H2b, H3, and ALB are revealed in all samples of plasma exosomes. Two histone-binding proteins, CHD5 and KDM6B, have been found in exosomes from HF plasma. The data obtained indicate that cirDNA preferentially binds to the outer membrane of exosomes by association with DNA-binding proteins.
The Clinical Picture of Patients Suffering from Hypophosphatasia—A Rare Metabolic Disease of Many Faces
Authors: Michałus Izabela , Gawlik Aneta , Wieczorek-Szukała Katarzyna , Lewiński Andrzej
Published: March 2022

Hypophosphatasia (HPP) is a rare, and usually diagnosed with delay, genetic disease caused by a mutation in the alkaline phosphatase liver/bone/kidney type (ALPL) gene. Low activity of the alkaline phosphatase (ALP) impairs the hydroxyapatite formation, reducing skeletal mineralization. The aim of the study was to present patients diagnosed with HPP. The data from the history and medical records of patients were analyzed. In the study group, one patient was diagnosed with perinatal type of HPP, three were diagnosed with infant variant, eight were diagnosed with children variant, two were diagnosed with odontohypophosphatasia, and two were diagnosed with the adult type of the disease. The most frequently presented symptoms included premature loss of teeth in 11/16 (68.75%) patients, bone deformities in 10/16 (62.5%) patients, chronic bone pain in 9/16 (56.25%) patients, and fractures in 8/16 (50%) patients. Reduction in bone mineral density in at least one examined projection has been found in 11/14 patients. Conclusions: The correct diagnosis of HPP is difficult due to the variety of types and clinical symptoms, as well as the very rare occurrence of this disease. Both lower and upper reference values of the determined biochemical parameters may be important in HPP diagnostics.
Nonlinear Statistical Features of the Seismicity in the Subduction Zone of Tehuantepec Isthmus, Southern México
Authors: Ramírez-Rojas Alejandro , Flores-Márquez Elsa Leticia
Published: March 2022

After the M8.2 main-shock occurred on 7 September 2017 at the Isthmus of Tehuantepec, Mexico, the spatial distribution of seismicity has showed a clear clusterization of earthquakes along the collision region of the Tehuantepec Transform/Ridge with the Middle America Trench off Chiapas. Furthermore, nowadays, the temporal rate of occurrence in the number of earthquakes has also showed a pronounced increase. On the basis of this behavior, we studied the sequence of magnitudes of the earthquakes which occurred within the Isthmus of Tehuantepec in southern Mexico from 2010 to 2020. Since big earthquakes are considered as a phase transition, after the M8.2 main-shock, one must expect changes in the Tehuantepec ridge dynamics, which can be observed considering that the b-value in the Gutenberg–Richter law, has also showed changes in time. The goal of this paper is to characterize the behavior of the seismic activity by using the Gutenberg–Richter law, multifractal detrended fluctuation analysis, visibility graph and nowcasting method. Those methods have showed important parameters in order to assess risk, the multifractality and connectivity. Our findings indicate, first that b-value shows a dependency on time, which is clearly described by our analyses based on nowcasting method, multifractality and visibility graph.
Selective Power-Loss-Protection Method for Write Buffer in ZNS SSDs
Authors: Yang Junseok , Lee Seokjun , Ahn Sungyong
Published: March 2022

Most SSDs (solid-state drives) use an internal DRAM (Dynamic Random Access Memory) to improve the I/O performance and extend SSD lifespan by absorbing write requests. However, this volatile memory does not guarantee the persistence of buffered data in the event of sudden power-off. Therefore, highly reliable enterprise SSDs employ power-loss-protection (PLP) logic to ensure the durability of buffered data using the back-up power of capacitors. The SSD must provide enough capacitors for the PLP in proportion to the size of the volatile buffer. Meanwhile, emerging ZNS (Zoned Namespace) SSDs are attracting attention because they can support many I/O streams that are useful in multi-tenant systems. Although ZNS SSDs do not use an internal mapping table unlike conventional block-interface SSDs, a large write buffer is required to provide many I/O streams. The reason is that each I/O stream needs its own write buffer for write buffering where the host can allocate separate zones to different I/O streams. Moreover, the larger capacity and more I/O streams the ZNS SSD supports, the larger write buffer is required. However, the size of the write buffer depends on the amount of capacitance, which is limited not only by the SSD internal space, but also by the cost. Therefore, in this paper, we present a set of techniques that significantly reduce the amount of capacitance required in ZNS SSDs, while ensuring the durability of buffered data during sudden power-off. First, we note that modern file systems or databases have their own solutions for data recovery, such as WAL (Write-ahead Log) and journal. Therefore, we propose a selective power-loss-protection method that ensures durability only for the WAL or journal required for data recovery, not for the entire buffered data. Second, to minimize the time taken by the PLP, we propose a balanced flush method that temporarily writes buffered data to multiple zones to maximize parallelism and preserves the data in its original location when power is restored. The proposed methods are implemented and evaluated by modifying FEMU (QEMU-based Flash Emulator) and RocksDB. According to experimental results, the proposed selective-PLP reduces the amount of capacitance by 50 to 90% while retaining the reliability of ZNS SSDs. In addition, the balanced flush method reduces the PLP latency by up to 96%.
Optimal Allocation of IaaS Cloud Resources through Enhanced Moth Flame Optimization (EMFO) Algorithm
Authors: Thiruvenkadam Srinivasan , Kim Hyung-Jin , Ra In-Ho
Published: March 2022

A new generation of computing resources is available to customers via IaaS, PaaS, and SaaS administrations, making cloud computing the most significant innovation in recent history for the general public. A virtual machine (VM) is configured, started, and maintained across numerous physical hosts using IaaS. In many cases, cloud providers (CPs) charge utility customers who have registered their premises with the utility registration authorities. Given the opposing aims of increasing customer demand fulfillment while decreasing costs and optimizing asset efficiency, efficient VM allocation is generally considered as one of the most difficult tasks for CPs to overcome. This paper proposes the Enhanced Moth Flame Optimization (EMFO) algorithm to provide a unique strategy for assigning virtual machines to suit customer requirements. The recommended approach is applied on Amazon’s EC2 after three distinct experiments are assumed. The utility of the proposed method is further shown by the use of well-known optimization techniques for effective VM allocation. The app was created using a Java-based programming language and then run on the Netbeans IDE 12.4 platform.
Abundance and Distribution of Foliage on Balsam Fir and White Spruce in Reference to Spruce Budworm Ecology and Absolute Population Density Estimation
Authors: Régnière Jacques , Sanders Chris
Published: March 2022

We describe the distribution and amount of foliage, expressed as foliated branch surface area, weight, or number of buds in the live crown of healthy open-grown and closed-canopy balsam fir and white spruce trees. Balsam fir and white spruce have very similar total foliage surface area and weight. The live crown of white spruce trees contains fewer buds than balsam fir of similar dimensions. Thus, bud density per unit foliage weight or surface area is higher in balsam fir than in white spruce. We also observed that buds tend to grow in clusters more often on balsam fir than on white spruce, and that larvae of the spruce budworm preferentially attack buds that grow in clusters. Equations were developed to predict the total surface area and weight of foliage as well as number of buds in the live crown for estimation of absolute population density of spruce budworm. These equations use diameter at breast height (DBH) and the number of nodes in the live crown as predictors. When data on the number of live nodes are unavailable, it can be estimated from tree height. Equations were also developed from which to estimate foliage area, weight or bud numbers from DBH only.
Different Stochastic Resonances Induced by Multiplicative Polynomial Trichotomous Noise in a Fractional Order Oscillator with Time Delay and Fractional Gaussian Noise
Authors: Yan Zhi , Guirao Juan L. G. , Saeed Tareq , Chen Huatao , Liu Xianbin
Published: March 2022

A general investigation on the mechanism of stochastic resonance is reported in a time-delay fractional Langevin system, which endues a nonlinear form multiplicative colored noise and fractional Gaussian noise. In terms of theoretical analysis, both the expressions of output steady-state amplitude and that of the first moment of system response are obtained by utilizing stochastic averaging method, fractional Shapiro and Laplace methods. Due to the presence of trichotomous colored noise, the excitation frequency can induce fresh multimodal Bona fide stochastic resonance, exhibiting much more novel dynamical behaviors than the non-disturbance case. It is verified that multimodal pattern only appears with small noise switching rate and memory damping order. The explicit expressions of critical noise intensity corresponding to the generalized stochastic resonance are given for the first time, by which it is determined that nonlinear form colored noise induces much more of a comprehensive resonant phenomena than the linear form. In the case of slow transfer rate noise, a newfangled phenomenon of double hypersensitive response induced by a variation in noise intensity is discovered and verified for the first time, with the necessary range of parameters for this phenomenon given. In terms of numerical scheme, an efficient and feasible algorithm for generating trichotomous noise is proposed, by which an algorithm based on the Caputo fractional derivative are applied. The numerical results match well with the analytical ones.
An Experimental Study of Strategic Voting and Accuracy of Verdicts with Sequential and Simultaneous Voting
Authors: Anderson Lisa R. , Holt Charles A. , Sieberg Katri K. , Freeborn Beth A.
Published: March 2022

In a model of simultaneous voting, Feddersen and Pesendorfer (1998) consider the possibility that jurors vote strategically, rather than sincerely reflecting their individual information. This results in the counterintuitive result that a jury is more likely to convict the innocent under a unanimity rule than under majority rule. Dekel and Piccione (2000) show that those unintuitive predictions also hold with sequential voting. In this paper, we report paired experiments with sequential and simultaneous voting under unanimity and majority rule. Observed behavior varies significantly depending on whether juries vote simultaneously or in sequence. We also find evidence that subjects use information inferred from prior votes in making their sequential voting decisions, but that information implied by being pivotal in simultaneous votes does not seem to be reliably processed.
Development of Dressing-Type Emulsion with Hydrocolloids from Butternut Squash Seed: Effect of Additives on Emulsion Stability
Authors: Quintana Somaris E. , Torregroza-Fuentes Edilbert , García Zapateiro Luis A.
Published: March 2022

Background: Natural ingredients have been employed to develop food products. Methods: Hydrocolloids from butternut squash seeds (HBSSs) were extracted with water at pH 3, 7, and 10 and characterized bromatologically and rheologically; then these HBSSs were used to stabilize the dressing-type emulsion by evaluating its physicochemical, rheological, and microstructural properties. Results: Hydrocolloids presented higher protein (from 20.43 to 39.39%) and carbohydrate (from 50.05 to 52.68%) content and rheological properties with a predominant elastic modulus. HBSSs extracted at pH 10 were used for the development of the dressing-type emulsion. The samples were stable during the storage period (15 days), with a good microstructural organization showing non-Newtonian fluid properties with shear-thinning behavior when the pseudoplasticity and the oil droplet size decreased with the addition of HBSS. Conclusions: Hydrocolloid constituents were detected surrounding the droplets of the emulsions, intensifying the effects of inner droplet interaction due to depletion events and a strong influence on the structure and physical stability. The hydrocolloids used to stabilize the dressing-type emulsions are additively promising in microstructured food design.
A Representation Protocol for Traditional Crafts
Authors: Zabulis Xenophon , Partarakis Nikolaos , Meghini Carlo , Dubois Arnaud , Manitsaris Sotiris , Hauser Hansgeorg , Magnenat Thalmann Nadia , Ringas Chris , Panesse Lucia , Cadi Nedjma , Baka Evangelia , Beisswenger Cynthia , Makrygiannis Dimitrios , Glushkova Alina , Padilla Brenda Elizabeth Olivas , Kaplanidi Danae , Tasiopoulou Eleana , Cuenca Catherine , Carre Anne-Laure , Nitti Vito , Adami Ilia , Zidianakis Emmanouil , Doulgeraki Paraskevi , Karouzaki Effie , Bartalesi Valentina , Metilli Daniele
Published: March 2022

A protocol for the representation of traditional crafts and the tools to implement this are proposed. The proposed protocol is a method for the systematic collection and organization of digital assets and knowledge, their representation into a formal model, and their utilization for research, education, and preservation. A set of digital tools accompanies this protocol that enables the online curation of craft representations. The proposed approach was elaborated and evaluated with craft practitioners in three case studies. Lessons learned are shared and an outlook for future work is provided.
Molecular Characterization of Prunus Cultivars from Romania by Microsatellite Markers
Authors: Butiuc-Keul Anca , Coste Ana , Postolache Dragoș , Laslo Vasile , Halmagyi Adela , Cristea Victoria , Farkas Anca
Published: March 2022

In Romania, Prunus species have great economic and social importance. With the introduction of new cultivars arises the need to preserve and characterize the local Prunus germplasm. Thus, a set of 24 polymorphic SSRs were selected for the overall characterization, including 10 peach, 11 apricot and 5 nectarine cultivars. The average number of alleles per locus (Na = 1.958), in addition to overall observed (Ho = 0.299) and expected heterozygosity (He = 0.286) were lower or comparable to those reported in similar studies, probably explained by the smaller number of analyzed cultivars restricted to a smaller geographic area. Among 26 genotypes a total of 101 alleles were identified, of which 46 alleles were in peach, 55 in apricot and 40 in nectarine, respectively. Six alleles from six loci (CPPCT-030, Pchgms-003, Pchgms-004, Pchgms-010, UDP97-401, UDP98-405) were common to all taxonomic groups. The most informative loci were BPPCT-025, Pchgms-021 and UDP96-001 in peach; BPPCT-025, BPPCT-001 and UDP96-001 in nectarine; and BPPCT-002, BPPCT-025, Pchgms-004, Pchgms-020 and Pchgms-021 in apricot. Clustering and genetic similarity analysis indicated that the degree of interspecific divergence in peach and nectarine cultivars was less than that in peach and apricot. These results will be useful to prevent confusion between cultivars, to improve breeding strategies and to benefit the management of Prunus cultivars bred in Romania.
Application of an Alternative Nutrient Replenishment Method to Electrical Conductivity-Based Closed-Loop Soilless Cultures of Sweet Peppers
Authors: Ahn Tae-In , Son Jung-Eek
Published: March 2022

The nutrient replenishment method primarily impacts the nutrient variations in a closed-loop soilless culture system. However, there is still a lack of systematic approaches for the effective way of nutrient replenishment. Our previous study theoretically derived and experimentally validated an alternative nutrient replenishment method expecting synchronized total fertilizer supply to total nutrient absorption by crops and lower concentration fluctuations than conventional methods. However, no individual nutrient management has been performed. The objective of this study was to apply individual nutrient management to the alternative nutrient replenishment technique under experimental- and commercial-scale electrical conductivity (EC)-based closed-loop soilless cultures. Automated nutrient solution mixing modules and sweet peppers grown on rockwool slabs were used. Nutrient concentrations and crop productivity were compared between the closed-loop system using the alternative nutrient replenishment and the conventional open-loop systems. During early treatment, rapid decreases in K+ and H2PO4− were observed in the closed-loop system. However, after the stock solution nutrient adjustment, the decreasing trend was stabilized and returned close to initial concentrations. No significant differences in sugar content, incidence of blossom-end rot, and productivity of sweet peppers were observed between the closed- and open-loop soilless cultures. We confirmed that the nutrient variation stabilizing effect of the alternative nutrient replenishment method was valid under nutrient adjustment conditions and had comparable nutrient management performance with the open-loop system.
Predictors of Prenatal Breastfeeding Self-Efficacy in Expectant Mothers with Gestational Diabetes Mellitus
Authors: Alyousefi Nada , Alemam Arwa , Altwaijri Dena , Alarifi Sarah , Alessa Haifa
Published: March 2022

Breastfeeding is beneficial for mothers with gestational diabetes mellitus (GDM). Saudi Arabia is considered one of the countries with the highest prevalence of GDM. Mothers with GDM have a low intention to breastfeed and are less likely to continue breastfeeding. This study aimed to measure breastfeeding self-efficacy among expectant mothers with GDM and quantify its determinants. This cross-sectional study recruited expectant mothers with GDM from an antenatal care clinic and queried them on breastfeeding knowledge and attitudes using the Arabic validated prenatal breastfeeding self-efficacy scale (PBSES). The study took place at the Medical City of King Saud University, during January–April 2021. The average PBSES score among 145 GDM Saudi participants was 64.07 ± 16.3. Higher academic level, previous satisfactory breastfeeding experiences, breastfeeding intention, six months or more breastfeeding experience, and health education were significantly positively correlated with PBSES score. A higher knowledge score was also correlated with a higher PBSES score (p = 0.002). Longer breastfeeding duration (β.197, p = 0.036), satisfactory previous breastfeeding experience (β.218, p = 0.020), and higher knowledge score (β.259, p = 0.004) were significant predictors of a high PBSES score. Breastfeeding self-efficacy is low among expectant Saudi mothers with GDM, especially those with unsatisfactory previous experience or low knowledge scores. Establishing systematic education about breastfeeding during antenatal care is recommended to improve breastfeeding experience and improve GDM outcomes.