bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Conversion of Amyloid-Beta 1-40 Oligomers to Mature Fibrils through a Self-Catalytic Bimolecular Process
Authors: Morel Bertrand , Carrasco-Jiménez María P. , Jurado Samuel , Conejero-Lara Francisco
Published: June 2021

The formation of fibrillar aggregates of the amyloid beta peptide (Aβ) in the brain is one of the hallmarks of Alzheimer’s disease (AD). A clear understanding of the different aggregation steps leading to fibrils formation is a keystone in therapeutics discovery. In a recent study, we showed that Aβ40 and Aβ42 form dynamic micellar aggregates above certain critical concentrations, which mediate a fast formation of more stable oligomers, which in the case of Aβ40 are able to evolve towards amyloid fibrils. Here, using different biophysical techniques we investigated the role of different fractions of the Aβ aggregation mixture in the nucleation and fibrillation steps. We show that both processes occur through bimolecular interplay between low molecular weight species (monomer and/or dimer) and larger oligomers. Moreover, we report here a novel self-catalytic mechanism of fibrillation of Aβ40, in which early oligomers generate and deliver low molecular weight amyloid nuclei, which then catalyze the rapid conversion of the oligomers to mature amyloid fibrils. This fibrillation catalytic activity is not present in freshly disaggregated low-molecular weight Aβ40 and is, therefore, a property acquired during the aggregation process. In contrast to Aβ40, we did not observe the same self-catalytic fibrillation in Aβ42 spheroidal oligomers, which could neither be induced to fibrillate by the Aβ40 nuclei. Our results reveal clearly that amyloid fibrillation is a multi-component process, in which dynamic collisions between different interacting species favor the kinetics of amyloid nucleation and growth.
Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades
Authors: Jalloh Ahmad , Flowers Antwoine , Hudson Charles , Chaput Dale , Guergues Jennifer , Stevens Stanley M. , Bickford Paula
Published: June 2021

Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.
One Hundred Candidate Genes and Their Roles in Drought and Salt Tolerance in Wheat
Authors: Urbanavičiūtė Ieva , Bonfiglioli Luca , Pagnotta Mario A.
Published: June 2021

Drought and salinity are major constraints to agriculture. In this review, we present an overview of the global situation and the consequences of drought and salt stress connected to climatic changes. We provide a list of possible genetic resources as sources of resistance or tolerant traits, together with the previous studies that focused on transferring genes from the germplasm to cultivated varieties. We explained the morphological and physiological aspects connected to hydric stresses, described the mechanisms that induce tolerance, and discussed the results of the main studies. Finally, we described more than 100 genes associated with tolerance to hydric stresses in the Triticeae. These were divided in agreement with their main function into osmotic adjustment and ionic and redox homeostasis. The understanding of a given gene function and expression pattern according to hydric stress is particularly important for the efficient selection of new tolerant genotypes in classical breeding. For this reason, the current review provides a crucial reference for future studies on the mechanism involved in hydric stress tolerance and the use of these genes in mark assistance selection (MAS) to select the wheat germplasm to face the climatic changes.
Potential of Naturally Derived Compounds in Telomerase and Telomere Modulation in Skin Senescence and Aging
Authors: Jacczak Barbara , Rubiś Błażej , Totoń Ewa
Published: June 2021

Proper functioning of cells—their ability to divide, differentiate, and regenerate—is dictated by genomic stability. The main factors contributing to this stability are the telomeric ends that cap chromosomes. Telomere biology and telomerase activity have been of interest to scientists in various medical science fields for years, including the study of both cancer and of senescence and aging. All these processes are accompanied by telomere-length modulation. Maintaining the key levels of telomerase component (hTERT) expression and telomerase activity that provide optimal telomere length as well as some nontelomeric functions represents a promising step in advanced anti-aging strategies, especially in dermocosmetics. Some known naturally derived compounds contribute significantly to telomere and telomerase metabolism. However, before they can be safely used, it is necessary to assess their mechanisms of action and potential side effects. This paper focuses on the metabolic potential of natural compounds to modulate telomerase and telomere biology and thus prevent senescence and skin aging.
Molecular Mechanisms of Drug Resistance in Glioblastoma
Authors: Dymova Maya A. , Kuligina Elena V. , Richter Vladimir A.
Published: June 2021

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).
Let’s Talk about Placental Sex, Baby: Understanding Mechanisms That Drive Female- and Male-Specific Fetal Growth and Developmental Outcomes
Authors: Meakin Ashley S. , Cuffe James S. M. , Darby Jack R. T. , Morrison Janna L. , Clifton Vicki L.
Published: June 2021

It is well understood that sex differences exist between females and males even before they are born. These sex-dependent differences may contribute to altered growth and developmental outcomes for the fetus. Based on our initial observations in the human placenta, we hypothesised that the male prioritises growth pathways in order to maximise growth through to adulthood, thereby ensuring the greatest chance of reproductive success. However, this male-specific “evolutionary advantage” likely contributes to males being less adaptable to shifts in the in-utero environment, which then places them at a greater risk for intrauterine morbidities or mortality. Comparatively, females are more adaptable to changes in the in-utero environment at the cost of growth, which may reduce their risk of poor perinatal outcomes. The mechanisms that drive these sex-specific adaptations to a change in the in-utero environment remain unclear, but an increasing body of evidence within the field of developmental biology would suggest that alterations to placental function, as well as the feto-placental hormonal milieu, is an important contributing factor. Herein, we have addressed the current knowledge regarding sex-specific intrauterine growth differences and have examined how certain pregnancy complications may alter these female- and male-specific adaptations.
Derivatives of Natural Chlorophylls as Agents for Antimicrobial Photodynamic Therapy
Authors: Suvorov Nikita , Pogorilyy Viktor , Diachkova Ekaterina , Vasil’ev Yuri , Mironov Andrey , Grin Mikhail
Published: June 2021

The rapid growth of drug-resistant bacteria all over the world has given rise to a major research challenge, namely a search for alternative treatments to which bacteria will be unable to develop resistance. Photodynamic therapy is an approach of this kind. It involves the use of photosensitizers in combination with visible light at a certain wavelength to excite the former and generate reactive oxygen species. Various synthetic heterocyclic compounds are used as photosensitizers. Of these, derivatives of natural chlorophylls have a special place due to their properties. This review deals with the use of such compounds in antimicrobial PDT.
Investigation of the Anti-Methicillin-Resistant Staphylococcus aureus Activity of (+)-Tanikolide- and (+)-Malyngolide-Based Analogues Prepared by Asymmetric Synthesis
Authors: Breheny Joseph , Kingston Cian , Doran Robert , Anes Joao , Martins Marta , Fanning Séamus , Guiry Patrick J.
Published: June 2021

Herein, we report antibacterial and antifungal evaluation of a series of previously prepared (+)-tanikolide analogues. One analogue, (4S,6S)-4-methyltanikolide, displayed promising anti-methicillin-resistant Staphylococcus aureus activity with a MIC of 12.5 µg/mL. Based on the antimicrobial properties of the structurally related (−)-malyngolide, two further analogues (4S,6S)-4-methylmalyngolide and (4R,6S)-4-methylmalyngolide bearing a shortened n-nonyl alkyl side chain were prepared in the present study using a ZrCl4-catalysed deprotection/cyclisation as the key step in their asymmetric synthesis. When these were tested for activity against anti-methicillin-resistant Staphylococcus aureus, the MIC increased to 50 µg/mL.
The PI-3-Kinase P110α Catalytic Subunit of T Lymphocytes Modulates Collagen-Induced Arthritis
Authors: Montes-Casado María , Ojeda Gloria , Criado Gabriel , Rojo José M. , Portolés Pilar
Published: June 2021

The phosphatidylinositol 3-kinase (PI3K) family of enzymes plays a determinant role in inflammation and autoimmune responses. However, the implication of the different isoforms of catalytic subunits in these processes is not clear. Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that entails innate and adaptive immune response elements in which PI3K is a potential hub for immune modulation. In a mouse transgenic model with T-cell-specific deletion of p110α catalytic chain (p110α−/−ΔT), we show the modulation of collagen-induced arthritis (CIA) by this isoform of PI3K. In established arthritis, p110α−/−ΔT mice show decreased prevalence of illness than their control siblings, higher IgG1 titers and lower levels of IL-6 in serum, together with decreased ex vivo Collagen II (CII)-induced proliferation, IL-17A secretion and proportion of naive T cells in the lymph nodes. In a pre-arthritis phase, at 13 days post-Ag, T-cell-specific deletion of p110α chain induced an increased, less pathogenic IgG1/IgG2a antibodies ratio; changes in the fraction of naive and effector CD4+ subpopulations; and an increased number of CXCR5+ T cells in the draining lymph nodes of the p110α−/−ΔT mice. Strikingly, T-cell blasts in vitro obtained from non-immunized p110α−/−ΔT mice showed an increased expression of CXCR5, CD44 and ICOS surface markers and defective ICOS-induced signaling towards Akt phosphorylation. These results, plus the accumulation of cells in the lymph nodes in the early phase of the process, could explain the diminished illness incidence and prevalence in the p110α−/−ΔT mice and suggests a modulation of CIA by the p110α catalytic chain of PI3K, opening new avenues of intervention in T-cell-directed therapies to autoimmune diseases.
Pancreatic Ductal Adenocarcinoma: The Dawn of the Era of Nuclear Medicine?
Authors: Montemagno Christopher , Cassim Shamir , De Leiris Nicolas , Durivault Jérôme , Faraggi Marc , Pagès Gilles
Published: June 2021

Pancreatic ductal adenocarcinoma (PDAC), accounting for 90–95% of all pancreatic tumors, is a highly devastating disease associated with poor prognosis. The lack of accurate diagnostic tests and failure of conventional therapies contribute to this pejorative issue. Over the last decade, the advent of theranostics in nuclear medicine has opened great opportunities for the diagnosis and treatment of several solid tumors. Several radiotracers dedicated to PDAC imaging or internal vectorized radiotherapy have been developed and some of them are currently under clinical consideration. The functional information provided by Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) could indeed provide an additive diagnostic value and thus help in the selection of patients for targeted therapies. Moreover, the therapeutic potential of β-- and α-emitter-radiolabeled agents could also overcome the resistance to conventional therapies. This review summarizes the current knowledge concerning the recent developments in the nuclear medicine field for the management of PDAC patients.
Regulatory Influence of Galanin and GALR1/GALR2 Receptors on Inflamed Uterus Contractility in Pigs
Authors: Jana Barbara , Całka Jarosław , Miciński Bartosz
Published: June 2021

Uterine inflammation is a very common and serious pathology in domestic animals, the development and progression of which often result from disturbed myometrial contractility. We investigated the effect of inflammation on the protein expression of galanin (GAL) receptor subtypes (GALR)1 and GALR2 in myometrium and their role in the contractile amplitude and frequency of an inflamed gilt uterus. The gilts of the E. coli and SAL groups received E. coli suspension or saline in their uteri, respectively, and only laparotomy was performed (CON group). Eight days later, the E. coli group developed severe acute endometritis and lowered GALR1 protein expression in the myometrium. Compared to the pretreatment period, GAL (10−7 M) reduced the amplitude and frequency in myometrium and endometrium/myometrium of the CON and SAL groups, the amplitude in both stripes and frequency in endometrium/myometrium of the E. coli group. In this group, myometrial frequency after using GAL increased, and it was higher than in other groups. GALR2 antagonist diminished the decrease in amplitude in myometrium and the frequency in endometrium/myometrium (SAL, E. coli groups) induced by GAL (10−7 M). GALR1/GALR2 antagonist and GAL (10−7 M) reversed the decrease in amplitude and diminished the decrease in frequency in both examined stripes (CON, SAL groups), and diminished the drop in amplitude and abolished the rise in the frequency in the myometrium (E. coli group). In summary, the inflammation reduced GALR1 protein expression in pig myometrium, and GALR1 and GALR2 participated in the contractile regulation of an inflamed uterus.
Is PTSD-Phenotype Associated with HPA-Axis Sensitivity?: The Endocannabinoid System in Modulating Stress Response in Rats
Authors: Danan Dor , Todder Doron , Zohar Joseph , Cohen Hagit
Published: June 2021

Endocannabinoids play a role in adaptation to stress and regulate the release of glucocorticoids in stressed and unstressed conditions. We recently found that basal corticosterone pulsatility may significantly impact the vulnerability for developing post-traumatic-stress-disorder (PTSD), suggesting that the endocannabinoid system may contribute to its development. To examine this, we exposed rats to predator scent stress (PSS). Behavioral reactions were recorded seven days post-PSS. Cerebrospinal fluid (CSF) was collected from anesthetized rats shortly after PSS exposure to determine the levels of 2-arachidonoyl glycerol (2-AG) and anandamide (AEA). To correlate between endocannabinoids and corticosterone levels, rats were placed in metabolic cages for urine collection. To assess the levels of endocannabinoids in specific brain regions, rats’ brains were harvested one day after behavioral analysis for staining and fluorescence quantification. Moreover, 2-AG was elevated in the CSF of PTSD-phenotype rats as compared with other groups and was inversely correlated with corticosterone urinary secretion. Eight days post-PSS exposure, hippocampal and hypothalamic 2-AG levels and hippocampal AEA levels were significantly more reduced in the PTSD-phenotype group compared to other groups. We posit that maladaptation to stress, which is propagated by an abnormal activation of endocannabinoids, mediates the subsequent stress-induced behavioral disruption, which, later, reduces neuronal the expression of endocannabinoids, contributing to PTSD symptomology.
An Imbalanced Image Classification Method for the Cell Cycle Phase
Authors: Jin Xin , Zou Yuanwen , Huang Zhongbing
Published: June 2021

The cell cycle is an important process in cellular life. In recent years, some image processing methods have been developed to determine the cell cycle stages of individual cells. However, in most of these methods, cells have to be segmented, and their features need to be extracted. During feature extraction, some important information may be lost, resulting in lower classification accuracy. Thus, we used a deep learning method to retain all cell features. In order to solve the problems surrounding insufficient numbers of original images and the imbalanced distribution of original images, we used the Wasserstein generative adversarial network-gradient penalty (WGAN-GP) for data augmentation. At the same time, a residual network (ResNet) was used for image classification. ResNet is one of the most used deep learning classification networks. The classification accuracy of cell cycle images was achieved more effectively with our method, reaching 83.88%. Compared with an accuracy of 79.40% in previous experiments, our accuracy increased by 4.48%. Another dataset was used to verify the effect of our model and, compared with the accuracy from previous results, our accuracy increased by 12.52%. The results showed that our new cell cycle image classification system based on WGAN-GP and ResNet is useful for the classification of imbalanced images. Moreover, our method could potentially solve the low classification accuracy in biomedical images caused by insufficient numbers of original images and the imbalanced distribution of original images.
Development of DNA Melt Curve Analysis for the Identification of Lepidopteran Pests in Almonds and Pistachios
Authors: Vulchi Rohith , Daane Kent M. , Wenger Jacob A.
Published: June 2021

Almonds and pistachios are fed upon by a diverse assemblage of lepidopteran insects, several of which are economically important pests. Unfortunately, identification of these pests can be difficult, as specimens are frequently damaged during collection, occur in traps with non-target species, and are morphologically similar up to their third instar. Here, we present a quantitative PCR based melt curve analysis for simple, rapid, and accurate identification of six lepidopteran pests of almonds and pistachios: navel orangeworm (Amyelois transitella), peach twig borer (Anarsia lineatella), oriental fruit moth (Grapholita molesta), obliquebanded leafroller (Choristoneura rosaceana), raisin moth (Cadra figulilella), and Indian meal moth (Plodia interpunctella). In this approach, the dissociation (melt) temperature(s) of a 658 bp section of cytochrome c oxidase subunit 1 was determined using quantitative PCR (qPCR). Within these six species, the distribution and the number of melt peak temperatures provide an unambiguous species level identification that is reproducible when unsheared DNA can be extracted. The test is robust across a variety of sampling approaches including insects removed from sticky card traps, museum specimens, and samples that were left in the field for up to 7 days. The melt curve’s simplicity allows it to be performed in any basic molecular biology laboratory with a quantitative PCR.
Phylogeographic Investigation of an Endangered Longhorn Beetle, Callipogon relictus (Coleoptera: Cerambycidae), in Northeast Asia: Implications for Future Restoration in Korea
Authors: Kang Ji Hyoun , Yi Dae-Am , Kuprin Alexander V. , Han Changdo , Bae Yeon Jae
Published: June 2021

The longhorn beetle, Callipogon (Eoxenus) relictus Semenov, is the only remnant species found in the Palearctic region, while all other Callipogon species are distributed mainly in Central America and partly in South America. This species has been placed in the first category (as ‘critically endangered’) of the Red Data Book in Russia and designated as one of the top-priority target species among all endangered invertebrate species for restoration in South Korea since 2006. Although its restricted distribution in Northeast Asia with a high conservational value has been highlighted, genetic features of C. relictus from different geographic regions remain unexplored. We first investigated the level of genetic diversity and phylogeographic patterns of C. relictus to evaluate the current conservational status and the feasibility of the implementation of a restoration program. The average genetic divergence of mitochondrial gene COI based on Kimura-2-parameter distance among the four regions in Russia, China, North Korea, and South Korea was 2.2%, which lies within the range of intraspecific levels. However, two separate clades with 3.8% divergence were identified, despite no geographical clustering of haplotypes. The linear pattern of the haplotype network with a high level of haplotype and nucleotide diversities suggests that the wide range of currently fragmented populations might be the remnant of genetically diverse populations in the past. This study will provide crucial information on the genetic characteristics and phylogeographic history of C. relictus, which will help to establish conservation strategies for this cherished insect species in Northeast Asia.
Mathematical Modelling of Conveyor-Belt Dryers with Tangential Flow for Food Drying up to Final Moisture Content below the Critical Value
Authors: Friso Dario
Published: June 2021

This work presents the mathematical modeling of the conveyor-belt dryer with tangential flow operating in co-current, which has the advantage of improving the preservation of the organoleptic and nutritional qualities of the dried food. On the one hand, it is a more cumbersome dryer than the perforated cross flow belt dryer but, on the other hand, it has a low air temperature in the final section where the product has a low moisture content and, therefore, it is more heat sensitive. The results of the mathematical modeling allowed a series of guidelines to be developed for a rational design of the conveyor-belt dryer with tangential flow for the specific case of the moisture content of the final product XF lower than the critical one XC (XF < XC). In fact, this work follows a precedent in which a mathematical model was developed through the differentiation of the drying rate equation along the dryer belt with the hypothesis that the final moisture content XF of the product was higher than the critical one XC. The relationships between the extensive quantities (air flow rate and product flow rate), the intensive quantities (temperatures, moisture content and enthalpies) and the dimensional ones (length and width of the belt) were then obtained. Finally, based on these relationships, the rules for an optimized design for XF < XC were obtained.
Risk Factors of Infection, Hospitalization and Death from SARS-CoV-2: A Population-Based Cohort Study
Authors: Castilla Jesús , Guevara Marcela , Miqueleiz Ana , Baigorria Fernando , Ibero-Esparza Carlos , Navascués Ana , Trobajo-Sanmartín Camino , Martínez-Baz Iván , Casado Itziar , Burgui Cristina , Ezpeleta Carmen ,   The Working Group for the Study of COVID-19 in Navarra
Published: June 2021

We conducted a prospective population-based cohort study to assess risk factors for infection, hospitalization, and death from SARS-CoV-2. The study comprised the people covered by the Health Service of Navarre, Spain. Sociodemographic variables and chronic conditions were obtained from electronic healthcare databases. Confirmed infections, hospitalizations, and deaths from SARS-CoV-2 were obtained from the enhanced epidemiological surveillance during the second SARS-CoV-2 epidemic surge (July–December 2020), in which diagnostic tests were widely available. Among 643,757 people, 5497 confirmed infections, 323 hospitalizations, 38 intensive care unit admissions, and 72 deaths from SARS-CoV-2 per 100,000 inhabitants were observed. A higher incidence of confirmed infection was associated with people aged 15–29 years, nursing home residents, healthcare workers, people born in Latin America or Africa, as well as in those diagnosed with diabetes, cardiovascular disease, chronic obstructive pulmonary disease (COPD), chronic kidney disease, dementia, severe obesity, hypertension and functional dependence. The risk of hospitalization in the population was associated with males, higher age, nursing home residents, Latin American or African origin, and those diagnosed with immunodeficiency, diabetes, cardiovascular disease, COPD, asthma, kidney disease, cerebrovascular disease, cirrhosis, dementia, severe obesity, hypertension and functional dependence. The risk of death was associated with males, higher age, nursing home residents, Latin American origin, low income level, immunodeficiency, diabetes, cardiovascular disease, COPD, kidney disease, dementia, and functional dependence. This study supports the prioritization of the older population, nursing home residents, and people with chronic conditions and functional dependence for SARS-CoV-2 prevention and vaccination, and highlights the need for additional preventive support for immigrants.
Impact of Prophylactic Hydroxychloroquine on People at High Risk of COVID-19: A Systematic Review and Meta-Analysis
Authors: Hernandez Adrian V. , Ingemi John , Sherman Michael , Pasupuleti Vinay , Barboza Joshuan J. , Piscoya Alejandro , Roman Yuani M. , White Charles M.
Published: June 2021

There are no proven prophylactic interventions for COVID-19. We systematically reviewed the efficacy of prophylactic hydroxychloroquine for COVID-19. Studies evaluating hydroxychloroquine for prophylaxis of COVID-19 were searched in several engines until 8 December 2020. Primary outcomes included RT-PCR positivity, COVID-19 infections (positive RT-PCR or compatible COVID-19 symptoms), and all-cause mortality. Random effects meta-analyses were performed for all outcomes. Five randomized controlled trials (RCTs) (n = 5579) and one cohort (n = 106) were included. Placebo was the comparator in four RCTs, and usual care in one RCT. Compared to the controls, five RCTs showed that hydroxychloroquine prophylaxis did not reduce RT-PCR positivity (RR 1.01, 95% CI 0.88–1.16), COVID-19 infection (RR 0.98, 95% CI 0.78–1.22), or all-cause mortality (RR 0.73, 95% CI 0.27–1.99). There were no differences of effects by pre- or post-exposure prophylaxis. Prophylaxis with hydroxychloroquine increased the risk of diarrhea, abdominal pain, or vomiting (RR 4.56, 95% CI 1.58–13.19). There were no effects of hydroxychloroquine on other secondary outcomes. Quality of evidence was low to very low for all outcomes. Hydroxychloroquine was not efficacious as a prophylaxis for COVID-19 infections, defined either as RT-PCR positivity or as a composite of RT-PCR positivity or compatible symptoms. Hydroxychloroquine did not reduce all-cause mortality, clinical worsening, or adverse events.
Preoperative Routine Laboratory Markers for Predicting Postoperative Recurrence and Death in Patients with Breast Cancer
Authors: Yoo Young-Chul , Park Seho , Kim Hyun-Joo , Jung Hyun-Eom , Kim Ji-Young , Kim Myoung-Hwa
Published: June 2021

Simple, convenient, and reliable preoperative prognostic indicators are needed to estimate the future risk of recurrences and guide the treatment decisions associated with breast cancer. We evaluated preoperative hematological markers related to recurrence and mortality and investigated independent risk factors for recurrence and mortality in patients after breast cancer surgery. We reviewed electronic medical records of patients with invasive breast cancer diagnosed at our tertiary institution between November 2005 and December 2010 and followed them until 2015. We compared two groups of patients classified according to recurrence or death and identified risk factors for postoperative outcomes. Data from 1783 patients were analyzed ultimately. Cancer antigen (CA) 15-3 and red cell distribution width (RDW) had the highest area under the curve values among several preoperative hematological markers for disease-free survival and overall survival (0.590 and 0.637, respectively). Patients with both preoperative CA 15-3 levels over 11.4 and RDW over 13.5 had a 1.7-fold higher risk of recurrence (hazard ratio (HR): 1.655; 95% confidence interval (CI): 1.154–2.374; p = 0.007) and mortality (HR: 1.723; 95% CI: 1.098–2.704; p = 0.019). In conclusion, relatively high preoperative RDW (>13.5) and CA 15-3 levels (>11.4) had the highest predictive power for mortality and recurrence, respectively. When RDW and CA 15-3 exceeded the cut-off value, the risk of recurrence and death also increased approximately 1.7 times.
New Early Warning Score: EMS Off-Label Use in Out-of-Hospital Patients
Authors: Semeraro Federico , Corona Giovanni , Scquizzato Tommaso , Gamberini Lorenzo , Valentini Anna , Tartaglione Marco , Scapigliati Andrea , Ristagno Giuseppe , Martella Carmela , Descovich Carlo , Picoco Cosimo , Gordini Giovanni
Published: June 2021

Background: The National Early Warning Score (NEWS) is an assessment scale of in-hospital patients’ conditions. The purpose of this study was to assess the appropriateness of a potential off-label use of NEWS by the emergency medical system (EMS) to facilitate the identification of critical patients and to trigger appropriate care in the pre-hospital setting. Methods: A single centre, longitudinal, prospective study was carried out between July and August 2020 in the EMS service of Bologna. Home patients with age ≥ 18 years old were included in the study. The exclusion criterion was the impossibility to collect all the parameters needed to measure NEWS. Results: A total of 654 patients were enrolled in the study. The recorded NEWS values increased along with the severity of dispatch priority code, the EMS return code, the emergency department triage code, and with patients’ age (r = 0.135; p = 0.001). The aggregated value of NEWS was associated with an increased risk of hospitalization (OR = 1.30 (1.17; 1.34); p < 0.0001). Conclusion: This study showed that the use of NEWS in the urgent and emergency care services can help patient assessment while not affecting EMS crew operation and might assist decision making in terms of severity-code assignment and resources utilization.
Cancer Stem Cells as a Source of Drug Resistance in Bone Sarcomas
Authors: Menéndez Sofía T. , Gallego Borja , Murillo Dzohara , Rodríguez Aida , Rodríguez René
Published: June 2021

Bone sarcomas are commonly characterized by a high degree of intra-tumor heterogeneity, which in part is due to the presence of subpopulations of tumor cells presenting stem cell properties. Similar to normal stem cells, these cancer stem cells (CSCs) display a drug resistant phenotype and therefore are responsible for relapses and tumor dissemination. Drug resistance in bone sarcomas could be enhanced/modulated during tumor evolution though the acquisition of (epi)-genetic alterations and the adaptation to changing microenvironments, including drug treatments. Here we summarize findings supporting the involvement of pro-stemness signaling in the development of drug resistance in bone sarcomas. This include the activation of well-known pro-stemness pathways (Wnt/β-Cat, NOTCH or JAT/STAT pathways), changes in the metabolic and autophagic activities, the alteration of epigenetic pathways, the upregulation of specific non-coding RNAs and the crosstalk with different microenvironmental factors. This altered signaling is expected to be translated to the clinic in the form of biomarkers of response and new therapies able to overcome drug resistance.
Reduced Quality of Life and Sexual Satisfaction in Isolated Hypogonadotropic Hypogonadism
Authors: Kałużna Małgorzata , Kompf Pola , Rabijewski Michał , Moczko Jerzy , Kałużny Jarosław , Ziemnicka Katarzyna , Ruchała Marek
Published: June 2021

(1) Background: Isolated hypogonadotropic hypogonadism (IHH) is a genetic condition characterized by impaired puberty and fertility. IHH can significantly impact patient health-related quality of life (HRQoL), sexual satisfaction (SS) and mood. (2) Methods: Participants included 132 IHH subjects (89 men and 43 women) and 132 sex- and age-matched controls. HRQoL, depressive symptoms, erectile dysfunction (ED), and SS were assessed in an online survey using the Zung Self-Rating Depression Scale (SDS), 15D instrument of HRQoL (15D), Sexual Satisfaction Questionnaire (SSQ), and 5-item International Index of Erectile Function (IIEF-5). (3) Results: QoL and SS were significantly lower in the IHH group vs. controls. There was a high rate of ED (53.2% vs. 33%, p = 0.008) and depressive symptoms (45.00 ± 17.00 vs. 32.00 ± 12.00, p < 0.001) in patients vs. controls. The age of patients at IHH diagnosis inversely correlated with their overall 15D scores. An alarming non-compliance rate was seen (51.6%). No differences were found between scores of patients receiving hormone replacement therapy (HRT) and untreated subjects in any of the scales. (4) Conclusions: The HRQoL, SS, ED, and depression levels observed in IHH patients, despite HRT, are alarming. Late IHH diagnosis may have a particularly negative impact on HRQoL. More attention should be devoted to HRT adherence and various HRQoL aspects of IHH patients.
Corneal Cross-Linking for Paediatric Keratoconus: A Systematic Review and Meta-Analysis
Authors: Kobashi Hidenaga , Hieda Osamu , Itoi Motohiro , Kamiya Kazutaka , Kato Naoko , Shimazaki Jun , Tsubota Kazuo ,   the Keratoconus Study Group of Japan
Published: June 2021

All corneal cross-linking techniques attenuated disease progression in patients with pediatric keratoconus for at least one year based on a meta-analysis. A standard and accelerated technique led to marked improvement in visual acuity. We determined the efficacy and safety of corneal cross-linking (CXL) in pediatric keratoconus by conducting a systematic review and meta-analysis. The PubMed and Cochrane databases were searched for relevant studies on the effects of standard, transepithelial, and/or accelerated CXL protocols in patients aged 18 years or younger. Standardized mean differences with 95% confidence intervals were calculated to compare the data collected at baseline and 12 months. The primary outcomes were maximum keratometry (Kmax) and uncorrected visual acuity (UCVA), and the secondary outcomes were the thinnest corneal thickness (TCT), best-corrected visual acuity (BCVA), and manifest refraction spherical equivalent or cylindrical refraction. Our search yielded 7913 publications, of which 26 were included in our systematic review and 21 were included in the meta-analysis. Standard CXL significantly improved the Kmax, UCVA, and BCVA, and significantly decreased the TCT. Accelerated CXL significantly improved UCVA and BCVA. In the transepithelial and accelerated-transepithelial CXL methods, each measurable parameter did not change after treatments. All CXL techniques attenuated disease progression in patients with pediatric keratoconus for at least one year. Standard and accelerated CXL led to marked improvement in visual acuity.
Prevalence and Risk Factors of CoronaVac Side Effects: An Independent Cross-Sectional Study among Healthcare Workers in Turkey
Authors: Riad Abanoub , Sağıroğlu Derya , Üstün Batuhan , Pokorná Andrea , Klugarová Jitka , Attia Sameh , Klugar Miloslav
Published: June 2021

Background: COVID-19 vaccine hesitancy is a serious threat to mass vaccination strategies that need to be accelerated currently in order to achieve a substantial level of community immunity. Independent (non-sponsored) studies have a great potential to enhance public confidence in vaccines and accelerate their uptake process. Methods: A nationwide cross-sectional study for the side effects (SE) of CoronaVac was carried out in February 2021 among Turkish healthcare workers who were recently vaccinated. The questionnaire inquired about local and systemic SEs that occurred in the short-term, within four weeks, following vaccination. Results: A total of 780 healthcare workers were included in this study; 62.5% of them experienced at least one SE. Injection site pain (41.5%) was the most common local SE, while fatigue (23.6%), headache (18.7%), muscle pain (11.2%) and joint pain (5.9%) were the common systemic SEs. Female healthcare workers (67.9%) were significantly more affected by local and systemic SEs than male colleagues (51.4%). Younger age, previous infection, and compromised health status (chronic illnesses and regular medicines uptake) can be associated with an increased risk of CoronaVac SEs; Conclusions: The independent research shows a higher prevalence of CoronaVac SEs than what is reported by phase I–III clinical trials. In general, the results of this study confirm the overall safety of CoronaVac and suggest potential risk factors for its SEs. Gender-based differences and SEs distribution among age groups are worth further investigation.
SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence
Authors: Dao Thi Loi , Hoang Van Thuan , Colson Philippe , Lagier Jean Christophe , Million Matthieu , Raoult Didier , Levasseur Anthony , Gautret Philippe
Published: June 2021

Background: We conducted this review to summarize the relation between viral mutation and infectivity of SARS-CoV-2 and also the severity of COVID-19 in vivo and in vitro. Method: Articles were identified through a literature search until 31 May 2021, in PubMed, Web of Science and Google Scholar. Results: Sixty-three studies were included. To date, most studies showed that the viral mutations, especially the D614G variant, correlate with a higher infectivity than the wild-type virus. However, the evidence of the association between viral mutation and severity of the disease is scant. A SARS-CoV-2 variant with a 382-nucleotide deletion was associated with less severe infection in patients. The 11,083G > U mutation was significantly associated with asymptomatic patients. By contrast, ORF1ab 4715L and S protein 614G variants were significantly more frequent in patients from countries where high fatality rates were also reported. The current evidence showed that variants of concern have led to increased infectivity and deteriorating epidemiological situations. However, the relation between this variant and severity of COVID-19 infection was contradictory. Conclusion: The COVID-19 pandemic continues to spread worldwide. It is necessary to anticipate large clinical cohorts to evaluate the virulence and transmissibility of SARS-CoV-2 mutants.
Endoscopic versus Surgical Intervention for Painful Obstructive Chronic Pancreatitis: A Systematic Review and Meta-Analysis
Authors: Ma Ka Wing , So Hoonsub , Shin Euisoo , Mok Janice Hoi Man , Yuen Kim Ho Kam , Cheung Tan To , Park Do Hyun
Published: June 2021

There is limited evidence on the standard care for painful obstructive chronic pancreatitis (CP), while comparisons of endoscopic and surgical modes for pain relief have yielded conflicting results from small sample sizes. We aimed to obtain a clear picture of the matter by a meta-analysis of these results. We searched the Pubmed, Embase, and Cochrane Library databases to identify studies comparing endoscopic and surgical treatments for painful obstructive CP. Pooled effects were calculated by the random effect model. Primary outcomes were overall pain relief (complete and partial), and secondary outcomes were complete and partial pain relief, complication rate, hospitalization duration, and endocrine insufficiency. Seven studies with 570 patients were included in the final analysis. Surgical drainage was associated with superior overall pain relief [OR 0.33, 95% CI 0.23–0.47, p < 0.001, I2 = 4%] and lesser incidence of endocrine insufficiency [OR 2.10, 95% CI 1.20–3.67, p = 0.01, I2 = 0%], but no significant difference in the subgroup of complete [OR 0.57, 95% CI 0.32–1.01, p = 0.054, I2 = 0%] or partial [OR 0.67, 95% CI 0.37–1.22, p = 0.19, I2 = 0%] pain relief, complication rates [OR 1.00, 95% CI 0.41–2.46, p = 0.99, I2 = 49%], and hospital stay [OR −0.54, 95% CI −1.23–0.15, p = 0.13, I2 = 87%] was found. Surgery is associated with significantly better overall pain relief and lesser endocrine insufficiency in patients with painful obstructive CP. However, considering the invasiveness of surgery, no significant differences in complete or partial pain relief, and heterogeneity of a few parameters between two groups, endoscopic drainage may be firstly performed and surgical drainage may be considered when endoscopic drainage fails.
Diagnostic and Interventional Role of Endoscopic Ultrasonography for the Management of Pancreatic Neuroendocrine Neoplasms
Authors: Melita Giuseppinella , Pallio Socrate , Tortora Andrea , Crinò Stefano Francesco , Macrì Antonio , Dionigi Gianlorenzo
Published: June 2021

Pancreatic neuroendocrine neoplasms (PanNENs) are relatively rare, but their incidence has increased significantly in the last decades. Precise diagnosis and prognostic stratification are crucial for proper patient management. Endoscopic ultrasound (EUS) is the modality of choice for diagnosis of solid pancreatic tumors, showing a higher tumor detection rate than other imaging modalities, especially for small size lesions. EUS also serves as a guide for preoperative sampling and other interventions. EUS-tissue acquisition is a safe and highly accurate technique for cyto/histological diagnosis of PanNENs with a well-demonstrated correlation between Ki-67 proliferation index values and tumor grading on EUS and surgical specimens according to the WHO 2017 classification. Furthermore, the possibility of a preoperative EUS-guided fine needle tattooing or fiducial markers placement may help the surgeon to locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments using either ethanol injection or radiofrequency ablation have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients unfit for surgery with functioning or non-functioning PanNENs. This article review highlights the current role of EUS in PanNENs management, focusing on the present and future applications of EUS-guided interventions.
Exploring the Enjoyment of the Intergenerational Physical Activity
Authors: Buonsenso Andrea , Fiorilli Giovanni , Mosca Cristiana , Centorbi Marco , Notarstefano Concetta C. , Di Martino Giulia , Calcagno Giuseppe , Intrieri Mariano , di Cagno Alessandra
Published: June 2021

Intergenerational physical activity could be a pleasant method to prevent elderly sedentary behaviors. The aim of this study is to provide a basis to develop an intergenerational physical activity between preschool children and elderly people. An assessing enjoyment three questionnaire survey was administered to 140 participants (aged 67.8 ± 9.1): the global physical activity questionnaire (GPAQ) assessing the sedentariness degree; the physical activity enjoyment scale (PACES-Q) assessing enjoyment for the physical activity usually practiced; the physical activity enjoyment scale (PACES-INT) assessing the enjoyment for a hypothetical intergenerational program. Successively, the sample was divided into subgroups based on age, gender, marital status, education, employment, sports background, sedentariness level and residential location. Four multichoice questions, aiming to have guidelines in organizing an intergenerational program, were used. A total of 44.3% of the sample found the physical activity practiced pleasant, whereas 81.5% enjoyed the intergenerational program (only 7.1% expressed a negative judgment). A separated one-way ANOVA showed significant differences in PACES-INT for gender, (p = 0.009), residential location, (p < 0.001) and employment (p = 0.004). About 80% of the sample would adhere to the intergenerational programs, despite the fatigue fear and logistic or family relationship problems.
Prediction of Exercise Capacity and Training Prescription from the 6-Minute Walk Test and Rating of Perceived Exertion
Authors: Porcari John P. , Foster Carl , Cress Maria L. , Larson Rachel , Lewis Hannah , Cortis Cristina , Doberstein Scott , Donahue Marc , Fusco Andrea , Radtke Kimberly
Published: June 2021

Walking tests, such as the 6-min walk test (6MWT), are popular methods of estimating peak oxygen uptake (VO2peak) in clinical populations. However, the strength of the distance vs. VO2peak relationship is not strong, and there are no equations for estimating ventilatory threshold (VT), which is important for training prescription and prognosis. Since the 6MWT is often limited by walking mechanics, prediction equations that include simple additional predictors, such as the terminal rating of perceived exertion (RPE), hold the potential for improving the prediction of VO2max and VT. Therefore, this study was designed to develop equations for predicting VO2peak and VT from performance during the 6MWT, on the basis of walking performance and terminal RPE. Clinically stable patients in a cardiac rehabilitation program (N = 63) performed the 6MWT according to the American Thoracic Society guidelines. At the end of each walk, the subject provided their terminal RPE on a 6–20 Borg scale. Each patient also performed a maximal incremental treadmill test with respiratory gas exchange to measure VO2peak and VT. There was a good correlation between VO2peak and 6MWT distance (r = 0.80) which was improved by adding the terminal RPE in a multiple regression formula (6MWT + RPE, R2 = 0.71, standard error of estimate, SEE = 1.3 Metabolic Equivalents (METs). The VT was also well correlated with walking performance, 6MWT distance (r = 0.80), and was improved by the addition of terminal RPE (6MWT + RPE, R2 = 0.69, SEE = 0.95 METs). The addition of terminal RPE to 6MWT distance improved the prediction of maximal METs and METs at VT, which may have practical applications for exercise prescription.