bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Knowledge on Functionality and Potential Therapeutic Uses of Donkey Milk
Authors: Martini Mina , Altomonte Iolanda , Tricò Domenico , Lapenta Riccardo , Salari Federica
Published: May 2021

The increase of knowledge on the composition of donkey milk has revealed marked similarities to human milk, which led to a growing number of investigations focused on testing the potential effects of donkey milk in vitro and in vivo. This paper examines the scientific evidence regarding the beneficial effects of donkey milk on human health. Most clinical studies report a tolerability of donkey milk in 82.6–98.5% of infants with cow milk protein allergies. The average protein content of donkey milk is about 18 g/L. Caseins, which are main allergenic components of milk, are less represented compared to cow milk (56% of the total protein in donkey vs. 80% in cow milk). Donkey milk is well accepted by children due to its high concentration of lactose (about 60 g/L). Immunomodulatory properties have been reported in one study in humans and in several animal models. Donkey milk also seems to modulate the intestinal microbiota, enhance antioxidant defense mechanisms and detoxifying enzymes activities, reduce hyperglycemia and normalize dyslipidemia. Donkey milk has lower calorie and fat content compared with other milks used in human nutrition (fat ranges from 0.20% to 1.7%) and a more favourable fatty acid profile, being low in saturated fatty acids (3.02 g/L) and high in alpha-linolenic acid (about 7.25 g/100 g of fat). Until now, the beneficial properties of donkey milk have been mostly related to whey proteins, among which β-lactoglobulin is the most represented (6.06 g/L), followed by α-lactalbumin (about 2 g/L) and lysozyme (1.07 g/L). So far, the health functionality of donkey milk has been tested almost exclusively on animal models. Furthermore, in vitro studies have described inhibitory action against bacteria, viruses, and fungi. From the literature review emerges the need for new randomized clinical trials on humans to provide stronger evidence of the potential beneficial health effects of donkey milk, which could lead to new applications as an adjuvant in the treatment of cardiometabolic diseases, malnutrition, and aging.
Research Progress on Oxidative Stress and Its Nutritional Regulation Strategies in Pigs
Authors: Hao Yue , Xing Mingjie , Gu Xianhong
Published: May 2021

Oxidative stress refers to the dramatic increase in the production of free radicals in human and animal bodies or the decrease in the ability to scavenging free radicals, thus breaking the antioxidation–oxidation balance. Various factors can induce oxidative stress in pig production. Oxidative stress has an important effect on pig performance and healthy growth, and has become one of the important factors restricting pig production. Based on the overview of the generation of oxidative stress, its effects on pigs, and signal transduction pathways, this paper discussed the nutritional measures to alleviate oxidative stress in pigs, in order to provide ideas for the nutritional research of anti-oxidative stress in pigs.
Genome-Wide Association Study Provides Insights into Important Genes for Reproductive Traits in Nelore Cattle
Authors: Sbardella Ana Paula , Watanabe Rafael Nakamura , da Costa Rebeka Magalhães , Bernardes Priscila Arrigucci , Braga Larissa Graciano , Baldi Rey Fernando Sebastián , Lôbo Raysildo Barbosa , Munari Danísio Prado
Published: May 2021

The identification of genomic regions associated with reproductive traits as well as their biological processes allows a better understanding of the phenotypic variability of these traits. This information could be applied to animal breeding programs to accelerate genetic gain. The aim of this study was to evaluate the association between single nucleotide polymorphisms (SNP) with a scrotal circumference at 365 days of age (SC365) and at 450 days of age (SC450), gestation length (GL) as a calf trait, age at first calving (AFC), accumulated productivity (ACP), heifer early calving until 30 months (HC30), and stayability (STAY) traits, in order to identify candidate genes and biological pathways associated with reproductive traits in Nelore cattle. The data set consisted of pedigree, phenotypes, and genotypes of Nelore cattle from the “Associação Nacional de Criadores e Pesquisadores” (ANCP). The association analyses were performed using the Weighted Single-Step Genome-Wide Association method; the regions, consisting of 10 consecutive SNP, which explained more than 0.5% of additive genetic variance, were considered as a significant association. A total of 3, 6, 7, 5, 10, 25, and 12 windows were associated with SC355, SC450, GL, AFC, ACP, HC30, and STAY, respectively. The results revealed genes with important functions for reproductive traits, such as fertility and precocity. Some genes were associated with more than one trait, among them CAMK1D, TASP1, ACOXL, RAB11FIP5, and SFXN5. Moreover, the genes were enriched in functional terms, like negative regulation of fat cell differentiation, fatty acid alpha-oxidation, and sphingolipids signaling pathway. The identification of the genes associated with the traits, as well as genes enriched in the terms and pathway mentioned above, should contribute to future biological validation studies and may be used as candidate genes in Nelore breeding programs.
Specific Seminal Plasma Fractions Are Responsible for the Modulation of Sperm–PMN Binding in the Donkey
Authors: Miró Jordi , Catalán Jaime , Marín Henar , Yánez-Ortiz Iván , Yeste Marc
Published: May 2021

While artificial insemination (AI) with frozen-thawed sperm results in low fertility rates in donkeys, the addition of seminal plasma, removed during cryopreservation, partially counteracts that reduction. Related to this, an apparent inflammatory reaction in jennies is induced following AI with frozen-thawed sperm, as a high amount of polymorphonuclear neutrophils (PMN) are observed within the donkey uterus six hours after AI. While PMN appear to select the sperm that ultimately reach the oviduct, two mechanisms, phagocytosis and NETosis, have been purported to be involved in that clearance. Remarkably, sperm interacts with PMN, but the presence of seminal plasma reduces that binding. As seminal plasma is a complex fluid made up of different molecules, including proteins, this study aimed to evaluate how different seminal plasma fractions, separated by molecular weight (<3, 3–10, 10–30, 30–50, 50–100, and >100 kDa), affect sperm–PMN binding. Sperm motility, viability, and sperm–PMN binding were evaluated after 0 h, 1 h, 2 h, 3 h, and 4 h of co-incubation at 38 °C. Two seminal plasma fractions, including 30–50 kDa or 50–100 kDa proteins, showed the highest sperm motility and viability. As viability of sperm not bound to PMN after 3 h of incubation was the highest in the presence of 30–50 and 50–100 kDa proteins, we suggest that both fractions are involved in the control of the jenny’s post-breeding inflammatory response. In conclusion, this study has shown for the first time that specific fractions rather than the entire seminal plasma modulate sperm–PMN binding within the donkey uterus. As several proteins suggested to be involved in the control of post-AI endometritis have a molecular weight between 30 and 100 kDa, further studies aimed at determining the identity of these molecules and evaluating their potential effect in vivo are much warranted.
Intestinal Microbes of Hooded Cranes (Grus monacha) Wintering in Three Lakes of the Middle and Lower Yangtze River Floodplain
Authors: Gu Jingjing , Zhou Lizhi
Published: May 2021

Intestinal microbes participate in life activities of the host, and are affected by external environmental factors. Different habitat sizes and protection status provide different external environmental selection pressures for the same wintering waterbirds, which may be reflected in their intestinal microbes. Hooded Cranes are vulnerable migratory waterbirds with similar numbers wintering at three different lakes in the middle and lower Yangtze River floodplain, Poyang, Caizi, and Shengjin Lakes. Here, we analyzed the characteristics of intestinal bacterial and fungal communities of Hooded Cranes wintering at the three lakes to clarify the effect of habitat size and protection status on intestinal microbes, using high-throughput sequencing technology. Our results showed that community composition and diversity of intestinal microbes were significantly different among lakes with different habitat size and protection status. The Hooded Cranes at Shengjin Lake (small) had higher intestinal microbial alpha-diversity (for both bacteria and fungi) than those at Poyang Lake (large), which might be induced by social behavior of more waterbirds per unit area. The Hooded Cranes at Caizi Lake (relatively poorly protected habitat) had more diverse and abundant intestinal potential pathogens than Shengjin Lake (well-protected habitat). Our results indicated that the environmental pressure of a habitat might affect intestinal microorganisms and more attention might be needed for the vulnerable waterbirds at the habitat of poor protection status.
Maternal Vaginal Colonization and Extended-Spectrum Beta-Lactamase-Producing Bacteria in Vietnamese Pregnant Women
Authors: Viet Nguyen Thanh , Van Du Vu , Thuan Nghiem Duc , Van Tong Hoang , Toan Nguyen Linh , Van Mao Can , Van Tuan Nguyen , Pallerla Srinivas Reddy , Nurjadi Dennis , Velavan Thirumalaisamy P. , Son Ho Anh
Published: May 2021

Extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) resistance to commonly prescribed drugs is increasing in Vietnam. During pregnancy, ESBL-E may predispose women to reproductive tract infections and increases the risk for neonatal morbidity. Vaginal colonization and infections by Escherichia coli and Klebsiella pneumoniae are seldom studied in Vietnam. In this study, we investigated ESBL-producing Enterobacterales in the birth canal of pregnant women. Between 2016 and 2020, vaginal swabs were collected from 3104 pregnant women (mean gestational age of 31 weeks) and inoculated onto MacConkey agar plates. Colonies were subjected to direct identification and antimicrobial susceptibility testing using the VITEK®-2 automated compact system and disk diffusion. ESBL production was determined phenotypically. E. coli, Klebsiella species were identified in 30% (918/3104) of the vaginal swabs, with E. coli being the most common (73%; 667/918). ESBL-production was detected in 47% (432/918) of Enterobacterales, with frequent multidrug-resistant phenotype. The overall prevalence of carbapenem resistance was low (8%). Over 20% of Klebsiella spp. were carbapenem-resistant. Pregnant women had a high prevalence of colonization and may transmit ESBL-E to neonates at birth, an important risk factor to be considered. The high rate of ESBL-producers and carbapenem resistance in Enterobacterales in Vietnam emphasizes the need for consequent surveillance and access to molecular typing.
Prevalence of Antimicrobial Resistance (AMR) Salmonella spp. and Escherichia coli Isolated from Broilers in the East Coast of Peninsular Malaysia
Authors: Ibrahim Shamsaldeen , Wei Hoong Loh , Lai Siong Yip , Mustapha Zaharuddin , C. W. Zalati C. W. Salma , Aklilu Erkihun , Mohamad Maizan , Kamaruzzaman Nor Fadhilah
Published: May 2021

Salmonella species (spp.) and Escherichia coli (E. coli) are the most common infectious pathogens in poultry. Antimicrobials are given either as growth promoters or as treatment, thereby increasing the possibility of the emergence of antimicrobial resistance (AMR). We determined the prevalence of AMR for both pathogens isolated from broiler farms in the East Coast of Peninsular Malaysia from 2018–2019. A total of 384 cloacal swabs were collected, followed by bacterial isolation, confirmation, and antimicrobial susceptibility tests. The overall prevalence of Salmonella spp. and E. coli were 6.5% and 51.8%, respectively. Salmonella spp. and E. coli displayed resistance towards the following antimicrobials: erythromycin (100% for both pathogens), chloramphenicol (76.2% and 84.5%, respectively), tetracycline (62% and 94.6%, respectively), ampicillin (47.7% and 87%, respectively), sulfamethoxazole/trimethoprim (42.9% and 83.3%, respectively), ciprofloxacin (4.8% and 23.8%, respectively), nalidixic acid (9.6% and 60.7%, respectively), streptomycin (19% and 66%, respectively), kanamycin (28.6% and 57%, respectively), cephalothin (0% and 11%, respectively), and gentamicin (0% and 20.2%, respectively). Multidrug resistance (MDR) was recorded in 82% of Salmonella spp. and 100% of E. coli. These findings demonstrate the high prevalence of AMR in both pathogens in broiler farms on the East Coast of Peninsular Malaysia. These findings could be attributed to the excessive use of antimicrobial agents by poultry farm owners. Enhanced control measures and a strong monitoring system should be urgently implemented in order to reduce the emergence of antimicrobial resistance.
Mechanical Performance of Gilsonite Modified Asphalt Mixture Containing Recycled Concrete Aggregate
Authors: Zuluaga-Astudillo Daniel Alberto , Rondón-Quintana Hugo Alexander , Zafra-Mejía Carlos Alfonso
Published: May 2021

Hot-mix asphalts exposed to hot weather and high traffic volumes can display rutting distress. A material that can be used to increase the stiffness of asphalt binders is gilsonite. On the other hand, from an environmental point of view, the virgin natural aggregates of asphalt mixtures can be replaced with recycled concrete aggregates. For these reasons, this study modified the asphalt binder with gilsonite by wet-process to improve rutting resistance, and replaced (by mass and volume) part of the coarse fraction of the aggregate with recycled concrete aggregate in two hot-mix asphalts with different gradations. Unlike other studies, a larger experimental phase was used here. Marshall, indirect tensile strength, resilient modulus, permanent deformation, fatigue resistance, and Cantabro tests were performed. An ANOVA test was carried out. If the replacement of the virgin aggregate by recycled concrete aggregates was made by volume, both materials (gilsonite and recycled concrete aggregate) could be used in hot-mix asphalts for thick-asphalt layers in high temperature climates and any level of traffic. The use of both materials in hot-mix asphalts is not recommended for thin-asphalt layers in low temperatures climates. It is not advisable to replace the aggregates by mass.
Assessment of the Impact of Electric Vehicle Batteries in the Non-Linear Control of DC Microgrids
Authors: Samuel Pierre , Eddaaif Rachid , González-Zumba Andrés , Clairand Jean-Michel
Published: May 2021

Several efforts need to be performed in transportation and energy production to mitigate the current environmental issues that are related to fossil fuel use. The implementation of DC microgrids and the use of electric vehicles seem to be an adequate solution. However, various technical challenges have to be addressed, like grid stability issues. Thus, this case report assesses the impact of an electric vehicle load in a DC microgrid, subject to nonlinear control theory. The EV battery pack is modeled and simulated. Subsequently, it is included as a load in an available model of nonlinear control of DC microgrids. The results demonstrate high stability with this new load and the feasibility of its implementation.
Aggregate and Particle Size Distribution of the Soil Sediment Eroded on Steep Artificial Slopes
Authors: Kubínová Romana , Neumann Martin , Kavka Petr
Published: May 2021

In this study, the particle size distribution (PSD) of the soil sediment from topsoil obtained from soil erosion experiments under different conditions was measured. Rainfall simulators were used for rain generation on the soil erosion plots with slopes 22°, 30°, 34° and length 4.25 m. The influence of the external factors (slope and initial state) on the particle and aggregate size distribution were evaluated by laser diffractometer (LD). The aggregate representation percentage in the eroded sediment was also investigated. It has been found that when the erosion processes are intensive (steep slope or long duration of the raining), the eroded sediment contains coarser particles and lower amounts of aggregates. Three methods for the soil particle analyses were tested: (i) conventional–sieving and hydrometer method; (ii) PARIO Soil Particle Analyzer combined with sieving; and (iii) laser diffraction (LD) using Mastersizer 3000. These methods were evaluated in terms of reproducibility of the results, time demands, and usability. It was verified that the LD has significant advantages compared to other two methods, especially the short measurement time for one sample (only 15 min per sample for LD) and the possibility to destroy soil aggregates using ultrasound which is much easier than using hexametaphosphate.
Capacitor Voltage Balancing with Online Controller Performance-Based Tuning for a Switch-Sharing-Based Multilevel Inverter
Authors: Ramli Zalifah , Jamaludin Jafferi , Abd Rahim Nasrudin , Azzuhri Saaidal Razalli
Published: May 2021

Switch-sharing-based multilevel inverters offer great advantages in terms of efficiency improvement and output quality enhancement for low-power photovoltaic (PV) applications. However, the capacitor voltage balancing issue may critically deteriorate the output voltages, and thus could nullify the aforementioned benefits. Hence, this paper proposes a capacitor voltage balancing solution based on a buck-boost converter with performance-based tuning controllers to address the issue. The proposed controllers are designed based on the proportional-integral (PI) configuration equipped with an online tuning mechanism. The main purpose of the online tuning mechanism is to fine tune the proportional gain according to the DC input voltage, based on the measured output current total harmonic distortion (THD) performance of the inverter, while at the same time preventing the controller from reaching a state of saturation. By using the actual measurement of current THD performance, online tuning accuracy can be improved since no ideal condition is assumed, and thus, the associated error can be minimized. Simulation and experimental results reveal that the capacitor voltages can be balanced at high modulation indexes with improved current harmonic performance able to be be acquired at the inverter’s output.
Test-Retest Reliability of Sole Morphology Measurements Using a Novel Single-Image-Based Pin-Array Impression Reconstruction Method
Authors: Chen Tsan-Yang , Kuo Chien-Chung , Hung Li-Wei , Lee Wei-Chun , Lo Jie-Hsing , Lu Hsuan-Lun , Lu Tung-Wu
Published: May 2021

Background: Assessment of the sole morphology provides a clinically useful measure of the foot condition, but existing methods are mostly limited to two-dimensional or non-weight-bearing conditions. The current study aimed to assess the reliability of a novel method called Single-Image-Based Pin-Array Impression Reconstruction Method (SIBPAIR) implemented on a commercial foot assessment system, and the intra-rater, inter-rater and inter-session reliability of the SIBPAIR-based protocol for three-dimensional sole morphological measurements. Methods: The reliability of the SIBPAIR method, and the intra-rater, inter-rater, and inter-session reliability of the SIBPAIR-based protocol in measuring morphological parameters of the sole were assessed by repeated measurements of fifteen young healthy adults by two male physical therapists, in terms of intra-class correlation coefficients (ICC) and standard error of measurement (SEM). Results and Conclusions: The SIBPAIR method was found to have very high reliability with very small SEM values, and the SIBPAIR-based protocol also showed very high intra-rater, inter-rater, and inter-session reliability with small SEM. These results indicate that accurate and reliable measurements could be obtained by following the protocol regardless of the rater’s experience or time of measurement. This will be useful for foot assessment and subsequent applications, such as design and manufacture of customized orthoses or shoes.
The Diurnal Variation in Stratospheric Ozone from MACC Reanalysis, ERA-Interim, WACCM, and Earth Observation Data: Characteristics and Intercomparison
Authors: Schanz Ansgar , Hocke Klemens , Kämpfer Niklaus , Chabrillat Simon , Inness Antje , Palm Mathias , Notholt Justus , Boyd Ian , Parrish Alan , Kasai Yasuko
Published: May 2021

In this study, we compare the diurnal variation in stratospheric ozone of the MACC (Monitoring Atmospheric Composition and Climate) reanalysis, ECMWF Reanalysis Interim (ERA-Interim), and the free-running WACCM (Whole Atmosphere Community Climate Model). The diurnal variation of stratospheric ozone results from photochemical and dynamical processes depending on altitude, latitude, and season. MACC reanalysis and WACCM use similar chemistry modules and calculate a similar diurnal cycle in ozone when it is caused by a photochemical variation. The results of the two model systems are confirmed by observations of the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES) experiment and three selected sites of the Network for Detection of Atmospheric Composition Change (NDACC) at Mauna Loa, Hawaii (tropics), Bern, Switzerland (midlatitudes), and Ny-Ålesund, Svalbard (high latitudes). On the other hand, the ozone product of ERA-Interim shows considerably less diurnal variation due to photochemical variations. The global maxima of diurnal variation occur at high latitudes in summer, e.g., near the Arctic NDACC site at Ny-Ålesund, Svalbard. The local OZORAM radiometer observes this effect in good agreement with MACC reanalysis and WACCM. The sensed diurnal variation at Ny-Ålesund is up to 8% (0.4 ppmv) due to photochemical variations in summer and negligible during the dynamically dominated winter. However, when dynamics play a major role for the diurnal ozone variation as in the lower stratosphere (100–20 hPa), the reanalysis models ERA-Interim and MACC which assimilate data from radiosondes and satellites outperform the free-running WACCM. Such a domain is the Antarctic polar winter where a surprising novel feature of diurnal variation is indicated by MACC reanalysis and ERA-Interim at the edge of the polar vortex. This effect accounts for up to 8% (0.4 ppmv) in both model systems. In summary, MACC reanalysis provides a global description of the diurnal variation of stratospheric ozone caused by dynamics and photochemical variations. This is of high interest for ozone trend analysis and other research which is based on merged satellite data or measurements at different local time.
Overview of COVID-19 Disease: Virology, Epidemiology, Prevention Diagnosis, Treatment, and Vaccines
Authors: Salahshoori Iman , Mobaraki-Asl Noushin , Seyfaee Ahmad , Mirzaei Nasirabad Nasrin , Dehghan Zahra , Faraji Mehrdad , Ganjkhani Mina , Babapoor Aziz , Shadmehr Seyede , Hamrang Ali
Published: May 2021

Coronaviruses belong to the “Coronaviridae family”, which causes various diseases, from the common cold to SARS and MERS. The coronavirus is naturally prevalent in mammals and birds. So far, six human-transmitted coronaviruses have been discovered. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan, China. Common symptoms include fever, dry cough, and fatigue, but in acute cases, the disease can lead to severe shortness of breath, hypoxia, and death. According to the World Health Organization (WHO), the three main transmission routes, such as droplet and contact routes, airborne transmission and fecal and oral for COVID-19, have been identified. So far, no definitive curative treatment has been discovered for COVID-19, and the available treatments are only to reduce the complications of the disease. According to the World Health Organization, preventive measures at the public health level such as quarantine of the infected person, identification and monitoring of contacts, disinfection of the environment, and personal protective equipment can significantly prevent the outbreak COVID-19. Currently, based on the urgent needs of the community to control this pandemic, the BNT162b2 (Pfizer), mRNA-1273 (Moderna), CoronaVac (Sinovac), Sputnik V (Gamaleya Research Institute, Acellena Contract Drug Research, and Development), BBIBP-CorV (Sinofarm), and AZD1222 (The University of Oxford; AstraZeneca) vaccines have received emergency vaccination licenses from health organizations in vaccine-producing countries. Vasso Apostolopoulos, Majid Hassanzadeganroudsari
Characterization of Direct Perturbations on Voltage-Gated Sodium Current by Esaxerenone, a Nonsteroidal Mineralocorticoid Receptor Blocker
Authors: Chang Wei-Ting , Wu Sheng-Nan
Published: May 2021

Esaxerenone (ESAX; CS-3150, Minnebro®) is known to be a newly non-steroidal mineralocorticoid receptor (MR) antagonist. However, its modulatory actions on different types of ionic currents in electrically excitable cells remain largely unanswered. The present investigations were undertaken to explore the possible perturbations of ESAX on the transient, late and persistent components of voltage-gated Na+ current (INa) identified from pituitary GH3 or MMQ cells. GH3-cell exposure to ESAX depressed the transient and late components of INa with varying potencies. The IC50 value of ESAX required for its differential reduction in peak or late INa in GH3 cells was estimated to be 13.2 or 3.2 μM, respectively. The steady-state activation curve of peak INa remained unchanged during exposure to ESAX; however, recovery of peak INa block was prolonged in the presence 3 μM ESAX. In continued presence of aldosterone (10 μM), further addition of 3 μM ESAX remained effective at inhibiting INa. ESAX (3 μM) potently reversed Tef-induced augmentation of INa. By using isosceles-triangular ramp pulse with varying durations, the amplitude of persistent INa measured at high or low threshold was enhanced by the presence of tefluthrin (Tef), in combination with the appearance of the figure-of-eight hysteretic loop; moreover, hysteretic strength of the current was attenuated by subsequent addition of ESAX. Likewise, in MMQ lactotrophs, the addition of ESAX also effectively decreased the peak amplitude of INa along with the increased current inactivation rate. Taken together, the present results provide a noticeable yet unidentified finding disclosing that, apart from its antagonistic effect on MR receptor, ESAX may directly and concertedly modify the amplitude, gating properties and hysteresis of INa in electrically excitable cells.
The Influence of Cross-Fostering on Alcohol Consumption and Depressive-Like Behaviors in HA and LA Mice: The Role of the Endogenous Opioid System
Authors: Nawrocka Agata , Poznański Piotr , Łazarczyk Marzena , Gorzałczyński Michał , Skiba Dominik , Wolińska Renata , Bujalska-Zadrożny Magdalena , Lutfy Kabirullah , Sadowski Bogdan , Sacharczuk Mariusz
Published: May 2021

The development of alcohol dependence and depression is determined by various genetic and environmental factors. In the presented study, we used high analgesia (HA) and low analgesia (LA) mouse lines, characterized by different endogenous opioid system activity and divergent blood–brain barrier permeability, to determine the influence of cross-fostering of these lines raised by surrogate mothers on ethanol consumption and development of depressive-like behaviors. We also investigated ethanol drinking by biological parents or surrogate mothers. Furthermore, we investigated whether these parental changes would alter the effect of naloxone on ethanol intake and depressive-like behaviors in offspring. Our results reveal that cross-fostering of HA and LA raised by surrogate mothers has a greater impact on depressive-like behaviors than ethanol consumption. Ethanol intake by biological parents substantially affected depressive-like behaviors and ethanol consumption in offspring. Moreover, ethanol intake by biological parents or an adoptive mother modified the effect of naloxone on ethanol consumption and preference and depressive-like behaviors in the HA offspring only. Together, these results indicate that cross-fostering differentially affects the effect of naloxone on alcohol consumption and the development of depression.
The Association between Anemia and Parkinson’s Disease: A Nested Case-Control Study Using a National Health Screening Cohort
Authors: Kim Ji , Oh Jae , Wee Jee , Min Chan , Yoo Dae , Choi Hyo
Published: May 2021

(1) Background: Controversy exists regarding the relationship between anemia and Parkinson’s disease (PD). This study aimed to evaluate the risk of PD related to anemia in the Korean population. (2) Methods: The Korean National Health Insurance Service-National Sample Cohort, which includes adults over 40 years of age, was assessed from 2002 to 2015. A total of 5844 PD patients were matched by age, sex, income, and region of residence with 23,376 control participants at a ratio of 1:4. The analyzed covariates included age, sex, blood pressure, fasting blood glucose, obesity, smoking status, and alcohol consumption. A multiple logistic regression analysis was conducted for case-control analyses. (3) Results: The adjusted odds ratio (OR) for the risk of PD associated with anemia was 1.09 after adjusting for potential confounders (95% confidence interval (CI) 1.01–1.18, p = 0.030). Among men younger than 70 years, the adjusted OR of PD was 1.34 (95% CI 1.13–1.60, p = 0.001). (4) Conclusions: Our findings suggest that anemia may increase the risk of PD, particularly in men younger than 70 years. Further research is required to elucidate the causal relationship between these two diseases.
Neurophysiological Assessments of Brain and Spinal Cord Associated with Lower Limb Functions in Children with Cerebral Palsy: A Protocol for Systematic Review and Meta-Analysis
Authors: Ubalde Leonard , Liang Jing-Nong
Published: May 2021

Background: Task-dependent neurophysiological adaptations in people with cerebral palsy have been examined using various techniques such as functional magnetic resonance imaging, peripheral nerve stimulation in order to assess H-reflexes, and transcranial magnetic stimulation. This activity-dependent plasticity is hypothesized to improve specific gross motor function in individuals with cerebral palsy. Although these adaptations have been examined extensively, most studies examined tasks utilizing the upper limbs. The aim of this review is to assess the neurophysiological adaptations of the central nervous system in individuals with cerebral palsy during lower limb functional tasks. Methods: A systematic review and meta-analysis will be conducted to evaluate the neurophysiological changes in the brain and spinal cord associated with lower extremity tasks in individuals with cerebral palsy. We will search within PubMed, MEDLINE, Embase, PsychINFO, and CINAHL using a predetermined search string to identify and evaluate relevant studies. Two independent reviewers will screen these studies against our inclusion criteria and risks of bias, and will extract the data from each study. A third reviewer will be used to resolve any disagreement regarding the inclusion of a study between reviewers. Randomized controlled trials as well as cross-sectional studies published in English 10 years before May 2021 that investigate the neurophysiological adaptations in the brain and spinal cord in people with cerebral palsy will be included if they meet the eligibility criteria. Primary outcomes will include scalar values of fractional anisotropy (FA), H-reflex gains or measures of amplitude, as well as motor cortex (M1) cortical excitability as measured by transcranial magnetic stimulation. Discussion: Since no identifiable data will be involved in this study, no ethical approval is required. Our results will provide insight into the neurophysiological adaptations in children with cerebral palsy, which will be useful in guiding directions for clinical decision making and future development of targeted interventions in pediatrics rehabilitation for children with cerebral palsy. Systematic review registration: The protocol for this systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42020215902).
Deficits in Early Sensory and Cognitive Processing Are Related to Phase and Nonphase EEG Activity in Multiple Sclerosis Patients
Authors: Sarrias-Arrabal Esteban , Eichau Sara , Galvao-Carmona Alejandro , Domínguez Elvira , Izquierdo Guillermo , Vázquez-Marrufo Manuel
Published: May 2021

Currently, there is scarce knowledge about the relation between spectral bands modulations and the basis of cognitive impairment in multiple sclerosis (MS). In this sense, analyzing the evoked or phase activity can confirm results from traditional event-related potential (ERP) studies. However, studying the induced or nonphase activity may be necessary to elucidate hidden compensatory or affected cognitive mechanisms. In this study, 30 remitting-relapsing multiple sclerosis patients and 30 healthy controls (HCs) matched in sociodemographic variables performed a visual oddball task. The main goal was to analyze phase and nonphase alpha and gamma bands by applying temporal spectral evolution (TSE) and its potential relation with cognitive impairment in these patients. The behavioural results showed slower reaction time and poorer accuracy in MS patients compared to controls. In contrast, the time-frequency analysis of electroencephalography (EEG) revealed a delay in latency and lower amplitude in MS patients in evoked and induced alpha compared to controls. With respect to the gamma band, there were no differences between the groups. In summary, MS patients showed deficits in early sensorial (evoked alpha activity) and cognitive processing (induced alpha activity in longer latencies), whereas the induced gamma band supported the hypothesis of its role in translation of attentional focus (induced activity) and did not show strong activity in this paradigm (visual oddball).
Clinical Outcomes of Biportal Endoscopic Interlaminar Decompression with Oblique Lumbar Interbody Fusion (OLIF): Comparative Analysis with TLIF
Authors: Lee Ho-Jin , Park Eugene J. , Ahn Jae-Sung , Kim Sang Bum , Kwon Youk-Sang , Park Young-Cheol
Published: May 2021

Oblique lumbar interbody fusion (OLIF) improves the spinal canal, with favorable clinical outcomes. However, it may not be useful for treating concurrent, severe central canal stenosis (SCCS). Therefore, we added biportal endoscopic spinal surgery (BESS) after OLIF, evaluated the combined procedure for one-segment fusion with clinical outcomes, and compared it to open conventional TLIF. Patients were divided into two groups: Group A underwent BESS with OLIF, and Group B were treated via TLIF. The length of hospital stay (LOS), follow-up period, operative time, estimated blood loss (EBL), fusion segment, complications, and clinical outcomes were evaluated. Clinical outcomes were measured using Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) scores, and the modified Macnab criteria. All the clinical parameters improved significantly after the operation in Group A. The only significant between-group difference was that the EBL was significantly lower in Group A. At the final follow-up, no clinical parameter differed significantly between the groups. No complications developed in either group. We suggest that our combination technique is a useful, alternative, minimally invasive procedure for the treatment of one-segment lumbar SCCS associated with foraminal stenosis or segmental instability.
Cognitive Impairment in Parkinson’s Disease: Epidemiology, Clinical Profile, Protective and Risk Factors
Authors: Gonzalez-Latapi Paulina , Bayram Ece , Litvan Irene , Marras Connie
Published: May 2021

Cognitive impairment is a common non-motor symptom in Parkinson’s Disease (PD) and an important source of patient disability and caregiver burden. The timing, profile and rate of cognitive decline varies widely among individuals with PD and can range from normal cognition to mild cognitive impairment (PD-MCI) and dementia (PDD). Beta-amyloid and tau brain accumulation, oxidative stress and neuroinflammation are reported risk factors for cognitive impairment. Traumatic brain injury and pesticide and tobacco exposure have also been described. Genetic risk factors including genes such as COMT, APOE, MAPT and BDNF may also play a role. Less is known about protective factors, although the Mediterranean diet and exercise may fall in this category. Nonetheless, there is conflicting evidence for most of the factors that have been studied. The use of inconsistent criteria and lack of comprehensive assessment in many studies are important methodological issues. Timing of exposure also plays a crucial role, although identification of the correct time window has been historically difficult in PD. Our understanding of the mechanism behind these factors, as well as the interactions between gene and environment as determinants of disease phenotype and the identification of modifiable risk factors will be paramount, as this will allow for potential interventions even in established PD.
Voxelwise Principal Component Analysis of Dynamic [S-Methyl-11C]Methionine PET Data in Glioma Patients
Authors: Martens Corentin , Debeir Olivier , Decaestecker Christine , Metens Thierry , Lebrun Laetitia , Leurquin-Sterk Gil , Trotta Nicola , Goldman Serge , Van Simaeys Gaetan
Published: May 2021

Recent works have demonstrated the added value of dynamic amino acid positron emission tomography (PET) for glioma grading and genotyping, biopsy targeting, and recurrence diagnosis. However, most of these studies are based on hand-crafted qualitative or semi-quantitative features extracted from the mean time activity curve within predefined volumes. Voxelwise dynamic PET data analysis could instead provide a better insight into intra-tumor heterogeneity of gliomas. In this work, we investigate the ability of principal component analysis (PCA) to extract relevant quantitative features from a large number of motion-corrected [S-methyl-11C]methionine ([11C]MET) PET frames. We first demonstrate the robustness of our methodology to noise by means of numerical simulations. We then build a PCA model from dynamic [11C]MET acquisitions of 20 glioma patients. In a distinct cohort of 13 glioma patients, we compare the parametric maps derived from our PCA model to these provided by the classical one-compartment pharmacokinetic model (1TCM). We show that our PCA model outperforms the 1TCM to distinguish characteristic dynamic uptake behaviors within the tumor while being less computationally expensive and not requiring arterial sampling. Such methodology could be valuable to assess the tumor aggressiveness locally with applications for treatment planning and response evaluation. This work further supports the added value of dynamic over static [11C]MET PET in gliomas.
Photosensitizing Medications and Skin Cancer: A Comprehensive Review
Authors: George Elisabeth , Baranwal Navya , Kang Jae , Qureshi Abrar , Drucker Aaron , Cho Eunyoung
Published: May 2021

(1) The incidence of skin cancer is increasing in the United States (US) despite scientific advances in our understanding of skin cancer risk factors and treatments. In vitro and in vivo studies have provided evidence that suggests that certain photosensitizing medications (PSMs) increase skin cancer risk. This review summarizes current epidemiological evidence on the association between common PSMs and skin cancer. (2) A comprehensive literature search was conducted to identify meta-analyses, observational studies and clinical trials that report on skin cancer events in PSM users. The associated risks of keratinocyte carcinoma (squamous cell carcinoma and basal cell carcinoma) and melanoma are summarized, for each PSM. (3) There are extensive reports on antihypertensives and statins relative to other PSMs, with positive and null findings, respectively. Fewer studies have explored amiodarone, metformin, antimicrobials and vemurafenib. No studies report on the individual skin cancer risks in glyburide, naproxen, piroxicam, chlorpromazine, thioridazine and nalidixic acid users. (4) The research gaps in understanding the relationship between PSMs and skin cancer outlined in this review should be prioritized because the US population is aging. Thus the number of patients prescribed PSMs is likely to continue to rise.
Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors
Authors: Mørup Nina , Stakaitis Rytis , Golubickaite Ieva , Riera Meritxell , Dalgaard Marlene Danner , Schierup Mikkel H. , Jørgensen Niels , Daugaard Gedske , Juul Anders , Almstrup Kristian
Published: May 2021

Circulating miRNAs secreted by testicular germ cell tumors (TGCT) show great potential as novel non-invasive biomarkers for diagnosis of TGCT. Seminal plasma (SP) represents a biofluid closer to the primary site. Here, we investigate whether small RNAs in SP can be used to diagnose men with TGCTs or the precursor lesions, germ cell neoplasia in situ (GCNIS). Small RNAs isolated from SP from men with TGCTs (n = 18), GCNIS-only (n = 5), and controls (n = 25) were sequenced. SP from men with TGCT/GCNIS (n = 37) and controls (n = 22) were used for validation by RT-qPCR. In general, piRNAs were found at lower levels in SP from men with TGCTs. Ten small RNAs were found at significantly (q-value < 0.05) different levels in SP from men with TGCT/GCNIS than controls. Random forests classification identified sets of small RNAs that could detect either TGCT/GCNIS or GCNIS-only with an area under the curve of 0.98 and 1 in ROC analyses, respectively. RT-qPCR validated hsa-miR-6782-5p to be present at 2.3-fold lower levels (p = 0.02) in the SP from men with TGCTs compared with controls. Small RNAs in SP show potential as novel biomarkers for diagnosing men with TGCT/GCNIS but validation in larger cohorts is needed.
Management of Low Rectal Cancer Complicating Ulcerative Colitis: Proposal of a Treatment Algorithm
Authors: Sensi Bruno , Bagaglini Giulia , Bellato Vittoria , Cerbo Daniele , Guida Andrea Martina , Khan Jim , Panis Yves , Savino Luca , Siragusa Leandro , Sica Giuseppe S.
Published: May 2021

Low rectal Carcinoma arising at the background of Ulcerative Colitis poses significant management challenges to the clinicians. The complex decision-making requires discussion at the multidisciplinary team meeting. The published literature is scarce, and there are significant variations in the management of such patients. We reviewed treatment protocols and operative strategies; with the aim of providing a practical framework for the management of low rectal cancer complicating UC. A practical treatment algorithm is proposed.
The Combination of Single-Cell and Next-Generation Sequencing Can Reveal Mosaicism for BRCA2 Mutations and the Fine Molecular Details of Tumorigenesis
Authors: Gráf Alexandra , Enyedi Márton Zsolt , Pintér Lajos , Kriston-Pál Éva , Jaksa Gábor , Bálind Árpád , Ezer Éva , Horváth Péter , Sükösd Farkas , Kiss Ernő , Haracska Lajos
Published: May 2021

Germline mutations in the BRCA1 and BRCA2 genes are responsible for hereditary breast and ovarian cancer syndrome. Germline and somatic BRCA1/2 mutations may define therapeutic targets and refine cancer treatment options. However, routine BRCA diagnostic approaches cannot reveal the exact time and origin of BRCA1/2 mutation formation, and thus, the fine details of their contribution to tumor progression remain less clear. Here, we establish a diagnostic pipeline using high-resolution microscopy and laser microcapture microscopy to test for BRCA1/2 mutations in the tumor at the single-cell level, followed by deep next-generation sequencing of various tissues from the patient. To demonstrate the power of our approach, here, we describe a detailed single-cell-level analysis of an ovarian cancer patient we found to exhibit constitutional somatic mosaicism of a pathogenic BRCA2 mutation. Employing next-generation sequencing, BRCA2 c.7795G>T, p.(Glu2599Ter) was detected in 78% of reads in DNA extracted from ovarian cancer tissue and 25% of reads in DNA derived from peripheral blood, which differs significantly from the expected 50% of a hereditary mutation. The BRCA2 mutation was subsequently observed at 17–20% levels in the normal ovarian and buccal tissue of the patient. Together, our findings suggest that this mutation occurred early in embryonic development. Characterization of the mosaic mutation at the single-cell level contributes to a better understanding of BRCA mutation formation and supports the concept that the combination of single-cell and next-generation sequencing methods is advantageous over traditional mutational analysis methods. This study is the first to characterize constitutional mosaicism down to the single-cell level, and it demonstrates that BRCA2 mosaicism occurring early during embryogenesis can drive tumorigenesis in ovarian cancer.
Circulating Tumor Cell Clusters Are Frequently Detected in Women with Early-Stage Breast Cancer
Authors: Reduzzi Carolina , Di Cosimo Serena , Gerratana Lorenzo , Motta Rosita , Martinetti Antonia , Vingiani Andrea , D’Amico Paolo , Zhang Youbin , Vismara Marta , Depretto Catherine , Scaperrotta Gianfranco , Folli Secondo , Pruneri Giancarlo , Cristofanilli Massimo , Daidone Maria Grazia , Cappelletti Vera
Published: May 2021

The clinical relevance of circulating tumor cell clusters (CTC-clusters) in breast cancer (BC) has been mostly studied using the CellSearch®, a marker-dependent method detecting only epithelial-enriched clusters. However, due to epithelial-to-mesenchymal transition, resorting to marker-independent approaches can improve CTC-cluster detection. Blood samples collected from healthy donors and spiked-in with tumor mammospheres, or from BC patients, were processed for CTC-cluster detection with 3 technologies: CellSearch®, CellSieve™ filters, and ScreenCell® filters. In spiked-in samples, the 3 technologies showed similar recovery capability, whereas, in 19 clinical samples processed in parallel with CellSearch® and CellSieve™ filters, filtration allowed us to detect more CTC-clusters than CellSearch® (median number = 7 versus 1, p = 0.0038). Next, samples from 37 early BC (EBC) and 23 metastatic BC (MBC) patients were processed using ScreenCell® filters for attaining both unbiased enrichment and marker-independent identification (based on cytomorphological criteria). At baseline, CTC-clusters were detected in 70% of EBC cases and in 20% of MBC patients (median number = 2, range 0–20, versus 0, range 0–15, p = 0.0015). Marker-independent approaches for CTC-cluster assessment improve detection and show that CTC-clusters are more frequent in EBC than in MBC patients, a novel finding suggesting that dissemination of CTC-clusters is an early event in BC natural history.