bluuebunny/crossref_metadata_2025 huggingface dataset:
Factorial Investigation of Cobalt Retention by Ti and Fe Oxides-Modified Carbon Nanotubes: Multivariate Against Univariate Analysis
Authors: Fasfous Ismail , El-Sheikh Amjad , Awwad Anas , Al-Degs Yahya , Fayyoumi Ebaa , Dawoud Jamal
Published: June 2021

Fe/Ti-oxides-modified-carbon nanotubes CNTs nanocomposites were prepared and tested toward Co removal from solution under different operational conditions. The final performance of the nanocomposites for Co was highly dependent on the type and loaded amount of the oxides. The nanocomposites were characterized by standard methods and the results evidenced that the presence of CNTs hampers the growth of Fe3O4 and TiO2 particles and forming smaller nano-particles leading to better Co removal from solution. Analysis of isotherms at different temperatures indicated that Co retention was two-fold increased upon adding Ti-oxides up to 90.2%. All isotherms were fairly presented using Langmuir-Freundlich isotherm and most surfaces have high heterogeneity particularly after deposition of oxides. The combined influence of the factors was investigated by running a multivariate analysis. An empirical equation was generated by principal component analysis (PCA) for predicting Co retention assuming different relationships and the binary-interaction behavior between factors was the most dominant: Co retention (mg/g) = 5.12 + 1.25Conc + 1.47Temp − 1.38CNT% − 6.03Ti% − 5.03Fe% − 0.01Conc2 + 0.12Temp2 − 0.55CNT%2 − 1.53Ti%2 − 3.44Fe%2 + 0.17Conc  ×  Temp + 0.07Conc × CNT% + 0.07Conc × Ti% + 0.10Conc × Fe% + 0.21Temp × CNT% + 0.10Temp × Ti% + 0.17Temp × Fe% − 1.67CNT% × Ti% − 1.45CNT% × Fe% − 4.11Ti% × Fe%. The most dominant factors on Co retention were temperature and concentration (positive linear correlation) and the positive interaction between temperature/concentration and temperature/CNTs mass. PCA indicated that the coefficient Temp × CNTs (+0.21) was higher than Temp × Ti% (+0.10). The negative coefficients of Ti/Fe with CNTs (1.45–4.11) indicated better Co retention at higher Ti/Fe loads and lower mass of CNTs. The results support that fact that incorporation of CNTs with Ti/Fe oxides may have a positive synergic impact on Co retention.
Lithium Chloride Exerts Differential Effects on Dentinogenesis and Osteogenesis in Primary Pulp Cultures
Authors: Vijaykumar Anushree , Mina Mina
Published: June 2021

Wnt/β-catenin signaling is known to play essential roles in odontoblast differentiation and reparative dentin formation. Various Wnt activators including LiCl have been increasingly studied for their effectiveness to induce repair of the dentin-pulp complex. LiCl is a simple salt thought to activate Wnt/β-catenin signaling by inhibiting GSK3β. Previous in vitro and in vivo studies showed that LiCl increased odontoblast differentiation and enhanced reparative dentin formation. However, the underlying molecular and cellular mechanisms by which LiCl regulates odontoblast and osteoblast differentiation during reparative dentinogenesis are not well-understood. Our in vitro studies show that exposure of early dental pulp progenitors to LiCl increased the survival and the pool of αSMA+ progenitors, leading to enhanced odontoblast and osteoblast differentiation. The positive effects of LiCl in the differentiation of osteoblasts and odontoblasts from αSMA+ progenitors are mediated by Wnt/β-catenin signaling. Our results also showed that continuous and late exposure of dental pulp cells to LiCl increased the expression of odontoblast markers through Wnt/β-catenin signaling, and the number of odontoblasts expressing DMP1-Cherry and DSPP-Cerulean transgenes. However, unlike the early treatment, both continuous and late treatments decreased the expression of Bsp and the expression of BSP-GFPtpz transgene. These observations suggest that prolonged treatment with LiCl in more mature cells of the dental pulp has an inhibitory effect on osteoblast differentiation. The inhibitory effects of LiCl on osteogenesis and Bsp were not mediated through Wnt/β-catenin signaling. These observations suggest that the effects of LiCl, and GSK3β antagonists on reparative dentinogenesis involve multiple pathways and are not specific to Wnt/β-catenin signaling.
Minimization of a Short Computer-Based Test in Reading
Authors: Schurig Michael , Jungjohann Jana , Gebhardt Markus
Published: June 2021

Formative tests and assessments have high potential in supporting learning, especially for students with special educational needs. One approach to gain assessment information on student learning is to monitor learning progress. For that, multiple repeated tests are often performed by practitioners. In order to be useful in practice, tests must meet various interdependent quality criteria. A property of tests that touches various criteria as the utility and economy is the length. A test has to be long enough to give a meaningful, reliable and comparable measure but short enough to be usable in classroom situations. An approach to evaluate and minimize the length of a computer-based test on sentence comprehension is introduced. It is shown that the test can be shortened from eight to 5 min while the estimation of the student´s abilities remains relatively stable for a random item order and a fixed item order variant. The consequences of test development of progress monitoring and the procedure for test time reduction for the different quality criteria are outlined. An approach to evaluate and minimize the length of a computer-based test by using a one parameter logistic model on a test of sentence comprehension (N = 761) is introduced. The data and the syntax is published in the OSF project https://osf.io/hnbs8/.
The Burden of Hormonal Disorders: A Worldwide Overview With a Particular Look in Italy
Authors: Crafa Andrea , Calogero Aldo E. , Cannarella Rossella , Mongioi’ Laura M. , Condorelli Rosita A. , Greco Emanuela A. , Aversa Antonio , La Vignera Sandro
Published: June 2021

Endocrine diseases have a considerable impact on public health from an epidemiological point of view and because they may cause long-term disability, alteration of the quality-of-life of the affected patients, and are the fifth leading cause of death. In this extensive review of the literature, we have evaluated the prevalence of the different disorders of endocrine interest in the world and Italy, highlighting their epidemiological, clinical, and economic impact.
Whether the CMIP5 Models Can Reproduce the Long-Range Correlation of Daily Precipitation?
Authors: Dong Tianyun , Zhao Shanshan , Mei Ying , Xie Xiaoqiang , Wan Shiquan , He Wenping
Published: June 2021

In this study, we investigated the performance of nine CMIP5 models for global daily precipitation by comparing with NCEP data from 1960 to 2005 based on the detrended fluctuation analysis (DFA) method. We found that NCEP daily precipitation exhibits long-range correlation (LRC) characteristics in most regions of the world. The LRC of daily precipitation over the central of North American continent is the strongest in summer, while the LRC of precipitation is the weakest for the equatorial central Pacific Ocean. The zonal average scaling exponents of NCEP daily precipitation are smaller in middle and high latitudes than those in the tropics. The scaling exponents are above 0.9 over the tropical middle and east Pacific Ocean for the year and four seasons. Most CMIP5 models can capture the characteristic that zonal mean scaling exponents of daily precipitation reach the peak in the tropics, and then decrease rapidly with the latitude increasing. The zonal mean scaling exponents simulated by CMCC-CMS, GFDL-ESM2G and IPSL-CM5A-MR show consistencies with those of NCEP, while BCC_CSM1.1(m) and FGOALS-g2 cannot capture the seasonal variations of daily precipitation’s LRC. The biases of scaling exponents between CMIP5 models and NCEP are smaller in the high latitudes, and even less than the absolute value of 0.05 in some regions, including Arctic Ocean, Siberian, Southern Ocean and Antarctic. However, for Western Africa, Eastern Africa, Tropical Eastern Pacific and Northern South America, the simulated biases of scaling exponents are greater than the absolute value of 0.05 for the year and all four seasons. In general, the spatial biases of LRC simulated by GFDL-ESM2G, HadGEM2-AO and INM-CM4 are relatively small, which indicating that the LRC characteristics of daily precipitation are well simulated by these models.
Soil Organic Carbon Stocks in Mixed-Deciduous and Coniferous Forests in Austria
Authors: Jandl Robert , Ledermann Thomas , Kindermann Georg , Weiss Peter
Published: June 2021

Question: We compared the soil organic carbon stock of the forests of an entire country. The objective of our research was establishing the differences between coniferous or deciduous forests with respect to soil carbon stocks. The question is relevant because coniferous forests are increasingly damaged by abiotic and biotic disturbances that are related to climate change. Deciduous forests are considered to be less vulnerable. Their soils are expected to be more persistent and reliable sinks for carbon dioxide.

Methods: Soil data are available from the Austrian Forest Soil Survey. Soils have been sampled on sites of the Austrian Forest Inventory. The data were stratified according to geology (calcareous vs. silicatic bedrock), orientation of the slopes, and forest type (coniferous vs. mixed-deciduous forest). These data were used to establish ground truth of soil organic carbon stocks. Further, we had simulation results of a coupled forest growth/soil carbon model. The scenarios built on the results of the Forest Inventory 2007/09 and reflect a business-as-usual forest management vs. a climate-change adaptation scenario where forest managers replace coniferous with deciduous forests if site conditions permit it. The simulations were performed with the forest growth simulator CÂLDIS and the soil carbon model Yasso07.

Results: Based on the Austrian Forest Soil Survey carbon stocks of coniferous forests were consistently higher than in mixed-deciduous forests. This result applies both for the organic litter layer and the mineral soil to a depth of 50 cm. The depth gradients of carbon were similar in both forest types. The simulation under a strong warming scenario showed an increase in the carbon stocks of soils when conifers are replaced by deciduous tree species. In the 150-year simulation the majority of forest sites will become suitable for deciduous forests. The build-up of a large soil organic carbon stock is driven by the stronger harvesting pressure on the remaining coniferous forests. Deciduous forests were in lesser demand and developed under a light forest intervention regime. However, toward the end of the century, when the temperature level is far above present levels, the soil organic carbon stocks declined.
Chondrodysplasias With Multiple Dislocations Caused by Defects in Glycosaminoglycan Synthesis
Authors: Dubail Johanne , Cormier-Daire Valérie
Published: June 2021

Chondrodysplasias with multiple dislocations form a group of severe disorders characterized by joint laxity and multiple dislocations, severe short stature of pre- and post-natal onset, hand anomalies, and/or vertebral anomalies. The majority of chondrodysplasias with multiple dislocations have been associated with mutations in genes encoding glycosyltransferases, sulfotransferases, and transporters implicated in the synthesis or sulfation of glycosaminoglycans, long and unbranched polysaccharides composed of repeated disaccharide bond to protein core of proteoglycan. Glycosaminoglycan biosynthesis is a tightly regulated process that occurs mainly in the Golgi and that requires the coordinated action of numerous enzymes and transporters as well as an adequate Golgi environment. Any disturbances of this chain of reactions will lead to the incapacity of a cell to construct correct glycanic chains. This review focuses on genetic and glycobiological studies of chondrodysplasias with multiple dislocations associated with glycosaminoglycan biosynthesis defects and related animal models. Strong comprehension of the molecular mechanisms leading to those disorders, mostly through extensive phenotypic analyses of in vitro and/or in vivo models, is essential for the development of novel biomarkers for clinical screenings and innovative therapeutics for these diseases.
Understanding the Pathophysiology of Exosomes in Schistosomiasis: A New Direction for Disease Control and Prevention
Authors: Yuan Yue , Zhao Jianping , Chen Min , Liang Huifang , Long Xin , Zhang Bixiang , Chen Xiaoping , Chen Qian
Published: June 2021

Schistosomiasis is a parasitic disease endemic to freshwater areas of Southeast Asia, Africa, and South America that is capable of causing serious damage to the internal organs. Recent studies have linked exosomes to the progression of schistosomiasis. These structures are important mediators for intercellular communication, assist cells to exchange proteins, lipids, and genetic material and have been shown to play critical roles during host–parasite interactions. This review aims to discuss the pathophysiology of exosomes in schistosomiasis and their roles in regulating the host immune response. Understanding how exosomes are involved in the pathogenesis of schistosomiasis may provide new perspectives in diagnosing and treating this neglected disease.
A Comparative Analysis of Coronavirus Nucleocapsid (N) Proteins Reveals the SADS-CoV N Protein Antagonizes IFN-β Production by Inducing Ubiquitination of RIG-I
Authors: Liu Yan , Liang Qi-Zhang , Lu Wan , Yang Yong-Le , Chen Ruiai , Huang Yao-Wei , Wang Bin
Published: June 2021

Coronaviruses (CoVs) are a known global threat, and most recently the ongoing COVID-19 pandemic has claimed more than 2 million human lives. Delays and interference with IFN responses are closely associated with the severity of disease caused by CoV infection. As the most abundant viral protein in infected cells just after the entry step, the CoV nucleocapsid (N) protein likely plays a key role in IFN interruption. We have conducted a comprehensive comparative analysis and report herein that the N proteins of representative human and animal CoVs from four different genera [swine acute diarrhea syndrome CoV (SADS-CoV), porcine epidemic diarrhea virus (PEDV), severe acute respiratory syndrome CoV (SARS-CoV), SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), infectious bronchitis virus (IBV) and porcine deltacoronavirus (PDCoV)] suppress IFN responses by multiple strategies. In particular, we found that the N protein of SADS-CoV interacted with RIG-I independent of its RNA binding activity, mediating K27-, K48- and K63-linked ubiquitination of RIG-I and its subsequent proteasome-dependent degradation, thus inhibiting the host IFN response. These data provide insight into the interaction between CoVs and host, and offer new clues for the development of therapies against these important viruses.
Individuality in the Immune Repertoire and Induced Response of the Sponge Halichondria panicea
Authors: Schmittmann Lara , Franzenburg Sören , Pita Lucía
Published: June 2021

The animal immune system mediates host-microbe interactions from the host perspective. Pattern recognition receptors (PRRs) and the downstream signaling cascades they induce are a central part of animal innate immunity. These molecular immune mechanisms are still not fully understood, particularly in terms of baseline immunity vs induced specific responses regulated upon microbial signals. Early-divergent phyla like sponges (Porifera) can help to identify the evolutionarily conserved mechanisms of immune signaling. We characterized both the expressed immune gene repertoire and the induced response to lipopolysaccharides (LPS) in Halichondria panicea, a promising model for sponge symbioses. We exposed sponges under controlled experimental conditions to bacterial LPS and performed RNA-seq on samples taken 1h and 6h after exposure. H. panicea possesses a diverse array of putative PRRs. While part of those PRRs was constitutively expressed in all analyzed sponges, the majority was expressed individual-specific and regardless of LPS treatment or timepoint. The induced immune response by LPS involved differential regulation of genes related to signaling and recognition, more specifically GTPases and post-translational regulation mechanisms like ubiquitination and phosphorylation. We have discovered individuality in both the immune receptor repertoire and the response to LPS, which may translate into holobiont fitness and susceptibility to stress. The three different layers of immune gene control observed in this study, - namely constitutive expression, individual-specific expression, and induced genes -, draw a complex picture of the innate immune gene regulation in H. panicea. Most likely this reflects synergistic interactions among the different components of immunity in their role to control and respond to a stable microbiome, seawater bacteria, and potential pathogens.
Enhanced Mechanical Properties of Fe-Mn-Al-C Low Density Steel via Aging Treatment
Authors: Kang Li , Yuan Hao , Li Hua-ying , Ji Ya-feng , liu Hai-tao , Liu Guang-ming
Published: June 2021

This study investigated the tensile properties and deformation behavior of an aged Fe-26Mn-6Al-1C (mass%) alloy with a stacking fault energy of approximately 60 mJ·m−2. The results show that an ordered phase with a “short-range ordering” (SRO) structure formed after aging at 550°C for 10 h, further increasing the aging time to 48 h. Lamellar second-phase precipitates appeared at the austenitic grain boundaries. The aged sample at 550°C for 10 h exhibited an enhanced tensile strength (∼898 MPa) without notably sacrificing uniform elongation (∼46.3%), which was mainly attributed to the relatively high strain hardening in the entire plastic deformation due to the synergistic effects of planar slip, twinning-induced plasticity (TWIP), microband-induced plasticity (MBIP), and especially the formation of short-range ordering.
Predictability in Contemporary Medicine
Authors: Ciulla Michele M.
Published: June 2021

Medical practice is increasingly coming under the guidance of statistical-mathematical models that are, undoubtedly, valuable tools but are also only a partial representation of reality. Indeed, given that statistics may be more or less adequate, a model is still a subjective interpretation of the researcher and is also influenced by the historical context in which it operates. From this opinion, I will provide a short historical excursus that retraces the advent of probabilistic medicine as a long process that has a beginning that should be sought in the discovery of the complexity of disease. By supporting the belonging of this evolution to the scientific domain it is also acknowledged that the underlying model can be imperfect or fallible and, therefore, confutable as any product of science. Indeed, it seems non-trivial here to recover these concepts, especially today where clinical decisions are entrusted to practical guidelines, which are a hybrid product resulting from the aggregation of multiple perspectives, including the probabilistic approach, to disease. Finally, before the advent of precision medicine, by limiting the use of guidelines to the original consultative context, an aged approach is supported, namely, a relationship with the individual patient.
Abnormal Coagulation Function of Patients With COVID-19 Is Significantly Related to Hypocalcemia and Severe Inflammation
Authors: Qi Xu , Kong Hui , Ding Wenqiu , Wu Chaojie , Ji Ningfei , Huang Mao , Li Tiantian , Wang Xinyu , Wen Jingli , Wu Wenjuan , Wu Mingjie , Huang Chaolin , Li Yu , Liu Yun , Tang Jinhai
Published: June 2021

This study aimed to detect, analyze, and correlate the clinical characteristics, blood coagulation functions, blood calcium levels, and inflammatory factors in patients with mild and severe COVID-19 infections. The enrolled COVID-19 infected patients were from Wuhan Jin Yin-tan Hospital (17 cases, Wuhan, China), Suzhou Infectious Disease Hospital (87 cases, Suzhou, China), and Xuzhou Infectious Disease Hospital (14 cases, Xuzhou, China). After admission, basic information was collected; X-ray and chest CT images were obtained; and data from routine blood tests, liver and kidney function, myocardial enzymes, electrolytes, blood coagulation function, (erythrocyte sedimentation rate) ESR, C-reactive protein (CRP), IL-6, procalcitonin (PCT), calcitonin, and other laboratory tests were obtained. The patients were grouped according to the clinical classification method based on the pneumonia diagnosis and treatment plan for new coronavirus infection (trial version 7) in China. The measurements from mild (56 cases) and severe cases (51 cases) were compared and analyzed. Most COVID-19 patients presented with fever. Chest X-ray and CT images showed multiple patchy and ground glass opacities in the lungs of COVID 19 infected patients, especially in patients with severe cases. Compared with patients with mild infection, patients with severe infection were older (p = 0.023) and had a significant increase in AST and BUN. The levels of CK, LDH, CK-MB, proBNP, and Myo in patients with severe COVID-19 infection were also increased significantly compared to those in patients with mild cases. Patients with severe COVID-19 infections presented coagulation dysfunction and increased D-dimer and fibrin degradation product (FDP) levels. Severe COVID-19 patients had low serum calcium ion (Ca2+) concentrations and high calcitonin and PCT levels and exhibited serious systemic inflammation. Ca2+ in COVID-19 patients was significantly negatively correlated with PCT, calcitonin, D-dimer, PFDP, ESR, CRP and IL-6. D-dimer in COVID-19 patients was a significantly positively correlated with CRP and IL-6. In conclusion, patients with severe COVID-19 infection presented significant metabolic dysfunction and abnormal blood coagulation, a sharp increase in inflammatory factors and calcitonin and procalcitonin levels, and a significant decrease in Ca2+. Decreased Ca2+ and coagulation dysfunction in COVID-19 patients were significantly correlated with each other and with inflammatory factors.
Autonomous Nervous Response During Sedation in Colonoscopy and the Relationship With Clinician Satisfaction
Authors: Hann Alexander , Gruss Sascha , Goetze Sebastian , Mehlhase Niklas , Frisch Stephan , Walter Benjamin , Walter Steffen
Published: June 2021

Background: Nurse assisted propofol sedation (NAPS) is a common method used for colonoscopies. It is safe and widely accepted by patients. Little is known, however, about the satisfaction of clinicians performing colonoscopies with NAPS and the factors that negatively influence this perception such as observer-reported pain events. In this study, we aimed to correlate observer-reported pain events with the clinicians' satisfaction with the procedure. Additionally, we aimed to identify patient biosignals from the autonomic nervous system (B-ANS) during an endoscopy that correlate with those pain events.

Methods: Consecutive patients scheduled for a colonoscopy with NAPS were prospectively recruited. During the procedure, observer-reported pain events, which included movements and paralinguistic sounds, were simultaneously recorded with different B-ANS (facial electromyogram (EMG), skin conductance level, body temperature and electrocardiogram). After the procedure, the examiners filled out the Clinician Satisfaction with Sedation Instrument (CSSI). The primary endpoint was the correlation between CSSI and observer-reported pain events. The second primary endpoint was the identification of B-ANS that make it possible to predict those events. Secondary endpoints included the correlation between CSSI and sedation depth, the frequency and dose of sedative use, polyps resected, resection time, the duration of the procedure, the time it took to reach the coecum and the experience of the nurse performing the NAPS. ClinicalTrials.gov: NCT03860779.

Results: 112 patients with 98 (88.5%) available B-ANS recordings were prospectively recruited. There was a significant correlation between an increased number of observer-reported pain events during an endoscopy with NAPS and a lower CSSI (r = −0.318, p = 0.001). Additionally, the EMG-signal from facial muscles correlated best with the event time points, and the signal significantly exceeded the baseline 30 s prior to the occurrence of paralinguistic sounds. The secondary endpoints showed that the propofol dose relative to the procedure time, the cecal intubation time, the time spent on polyp removal and the individual nurse performing the NAPS significantly correlated with CSSI.

Conclusion: This study shows that movements and paralinguistic sounds during an endoscopy negatively correlate with the satisfaction of the examiner measured with the CSSI. Additionally, an EMG of the facial muscles makes it possible to identify such events and potentially predict their occurrence.
The Risk of COVID-19 Related Hospitalsation, Intensive Care Unit Admission and Mortality in People With Underlying Asthma or COPD: A Systematic Review and Meta-Analysis
Authors: Pardhan Shahina , Wood Samantha , Vaughan Megan , Trott Mike
Published: June 2021

Background: Several underlying diseases have been associated with unfavorable COVID-19 related outcomes including asthma and Chronic Obstructive Pulmonary Disease (COPD), however few studies have reported risks that are adjusted for confounding variables. This study aimed to examine the adjusted risk of COVID-19 related hospitalsation, intensive care unit (ICU) admission, and mortality in patients with vs. without asthma or COPD.

Methods: A systematic review of major databases was undertaken for studies published between 1/12/2019 and 19/4/2021. Studies reporting the adjusted (for one or more confounder) risks of either hospitalsation, ICU admission, or mortality in asthmatics or COPD patients (control group = no asthma or no COPD) were identified. Risk of bias was determined via the QUIPS tool. A random effect meta-analysis was undertaken.

Findings: 37 studies were eligible for analysis, with a total of 1,678,992 participants. The pooled ORs of COVID-19 hospitalsation in subjects with asthma and COPD was 0.91 (95% CI 0.76–1.09) and 1.37 (95% CI 1.29–1.46), respectively. For ICU admission, OR in subjects with asthma and COPD was 0.89 (95% CI 0.74–1.07) and 1.22 (95% CI 1.04–1.42), respectively. For mortality, ORs were 0.88 (95% CI 0.77–1.01) and 1.25 (95% CI 1.08–1.34) for asthma and COPD, respectively. Further, the pooled risk of mortality as measured via Cox regression was 0.93 (95% CI 0.87–1.00) for asthma and 1.30 (95% CI 1.17–1.44) for COPD. All of these findings were of a moderate level of certainty.

Interpretation: COPD was significantly associated with COVID-19 related hospital admission, ICU admission, and mortality. Asthma was not associated with negative COVID-19 related health outcomes. Individuals with COPD should take precautions to limit the risk of COVID-19 exposure to negate these potential outcomes. Limitations include differing population types and adjustment for differing cofounding variables. Practitioners should note these findings when dealing with patients with these comorbidities.

Review Protocol Registration:https://www.crd.york.ac.uk/prospero/.
Rapid Detection of Imipenem Resistance in Gram-Negative Bacteria Using Tabletop Scanning Electron Microscopy: A Preliminary Evaluation
Authors: Haddad Gabriel , Fontanini Anthony , Bellali Sara , Takakura Tatsuki , Ominami Yusuke , Hisada Akiko , Hadjadj Linda , Rolain Jean-Marc , Raoult Didier , Bou Khalil Jacques Yaacoub
Published: June 2021

Background: Enabling faster Antimicrobial Susceptibility Testing (AST) is critical, especially to detect antibiotic resistance, to provide rapid and appropriate therapy and to improve clinical outcomes. Although several standard and automated culture-based methods are available and widely used, these techniques take between 18 and 24 h to provide robust results. Faster techniques are needed to reduce the delay between test and results.

Methods: Here we present a high throughput AST method using a new generation of tabletop scanning electron microscope, to evaluate bacterial ultra-structural modifications associated with susceptibilities to imipenem as a proof of concept. A total of 71 reference and clinical strains of Gram-negative bacteria were used to evaluate susceptibility toward imipenem after 30, 60, and 90 min of incubation. The length, width and electron density of bacteria were measured and compared between imipenem susceptible and resistant strains.

Results: We correlated the presence of these morphological changes to the bacterial susceptibility and their absence to the bacterial resistance (e.g., Pseudomonas aeruginosa length without [2.24 ± 0.61 μm] and with [2.50 ± 0.68 μm] imipenem after 30 min [p = 3.032E-15]; Escherichia coli width without [0.92 ± 0.07 μm] and with [1.28 ± 0.19 μm] imipenem after 60 min [p = 1.242E-103]). We validated our method by a blind test on a series of 58 clinical isolates where all strains were correctly classified as susceptible or resistant toward imipenem.

Conclusion: This method could be a potential tool for rapidly identifying carbapenem-resistance in Enterobacterales in clinical microbiology laboratories in <2 h, allowing the empirical treatment of patients to be rapidly adjusted.
Lactobacillus-Based Probiotics Reduce the Adverse Effects of Stress in Rodents: A Meta-analysis
Authors: Mindus Claire , Ellis Jennifer , van Staaveren Nienke , Harlander-Matauschek Alexandra
Published: June 2021

Lactobacillus species play a critical role in the bidirectional communication between the gut and the brain. Consequently, they have the potential to aid in the treatment of psychological disorders. The impact of Lactobacillus supplementation on the stress responses triggering psychological disorders has not been systematically reviewed. Therefore, the aim of this meta-analysis is to summarize the body of research assessing the effects of Lactobacillus-based probiotics in rodents that underwent an experimental stress treatment or not. The duration of immobility in a Forced Swim Test (FST) was the outcome used to measure changes induced by various treatments. Four online databases were systematically searched for relevant studies published in English. Fourteen studies meeting the criteria were included in the meta-analysis. The effects of probiotic supplementation and stress treatment on the duration of immobility in the FST were analyzed using a generalized linear mixed model. Publication bias was evaluated by funnel plots. Our analysis shows that Lactobacillus-based probiotic supplements significantly reduce immobility in the FST (P < 0.001) in stressed rodents. However, probiotics did not affect the rodents that did not undergo the stress treatment (P = 0.168). These findings provide a better understanding of the potential of Lactobacillus-based probiotics for the management of stress-induced behavior.
Two Distinct Clinical Phenotypes of Bulbar Motor Impairment in Amyotrophic Lateral Sclerosis
Authors: Stipancic Kaila L. , Yunusova Yana , Campbell Thomas F. , Wang Jun , Berry James D. , Green Jordan R.
Published: June 2021

Objective: Understanding clinical variants of motor neuron diseases such as amyotrophic lateral sclerosis (ALS) is critical for discovering disease mechanisms and across-patient differences in therapeutic response. The current work describes two clinical subgroups of patients with ALS that, despite similar levels of bulbar motor involvement, have disparate clinical and functional speech presentations.

Methods: Participants included 47 healthy control speakers and 126 speakers with ALS. Participants with ALS were stratified into three clinical subgroups (i.e., bulbar asymptomatic, bulbar symptomatic high speech function, and bulbar symptomatic low speech function) based on clinical metrics of bulbar motor impairment. Acoustic and lip kinematic analytics were derived from each participant's recordings of reading samples and a rapid syllable repetition task. Group differences were reported on clinical scales of ALS and bulbar motor severity and on multiple speech measures.

Results: The high and low speech-function subgroups were found to be similar on many of the dependent measures explored. However, these two groups were differentiated on the basis of an acoustic measure used as a proxy for tongue movement.

Conclusion: This study supports the hypothesis that high and low speech-function subgroups do not differ solely in overall severity, but rather, constitute two distinct bulbar motor phenotypes. The findings suggest that the low speech-function group exhibited more global involvement of the bulbar muscles than the high speech-function group that had relatively intact lingual function. This work has implications for clinical measures used to grade bulbar motor involvement, suggesting that a single bulbar measure is inadequate for capturing differences among phenotypes.
Establishment of Carotid Artery Dissection and MRI Findings in a Swine Model
Authors: Peng Jing , Wu Min , Doycheva Desislava Met , He Yi , Huang Qiongzhen , Chen Wei , Matei Nathanael , Ding Jun , Chen Kangning , Xu Ningbo , Zhou Zhenhua
Published: June 2021

Carotid artery dissection (CAD) is the leading cause of ischemic stroke in young patients; however, the etiology and pathophysiology of CAD remain largely unknown. In our study, two types of dissections (length × width: 1.5 cm × 1/3 circumference of intima, Group I, n = 6; or 1.5 cm × 2/3 circumference of intima, Group II, n = 6) were created between the media and intima. Ultrasound (within 2 h after dissection) showed a dissociated intima in the lumen and obstructed blood flow in the surgical area. Digital subtraction angiography (DSA, 72 h after dissection), magnetic resonance imaging (MRI, 72 h after dissection), and hematoxylin–eosin (H&E, 7 days after dissection) staining confirmed stenosis (33.67 ± 5.66%) in Group I and total occlusion in Group II. In 10 out of 12 swine, the CAD model was established using a detacher and balloon dilation, and morphological outcomes (stenosis or occlusion) after CAD were determined by the size of intimal incision.
Imaging the Pathophysiology of Essential Tremor—A Systematic Review
Authors: Holtbernd Florian , Shah N. Jon
Published: June 2021

Background: The pathophysiology underlying essential tremor (ET) still is poorly understood. Recent research suggests a pivotal role of the cerebellum in tremor genesis, and an ongoing controversy remains as to whether ET constitutes a neurodegenerative disorder. In addition, mounting evidence indicates that alterations in the gamma-aminobutyric acid neurotransmitter system are involved in ET pathophysiology. Here, we systematically review structural, functional, and metabolic neuroimaging studies and discuss current concepts of ET pathophysiology from an imaging perspective.

Methods: We conducted a PubMed and Scopus search from 1966 up to December 2020, entering essential tremor in combination with any of the following search terms and their corresponding abbreviations: positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and gamma-aminobutyric acid (GABA).

Results: Altered functional connectivity in the cerebellum and cerebello-thalamico-cortical circuitry is a prevalent finding in functional imaging studies. Reports from structural imaging studies are less consistent, and there is no clear evidence for cerebellar neurodegeneration. However, diffusion tensor imaging robustly points toward microstructural cerebellar changes. Radiotracer imaging suggests that the dopaminergic axis is largely preserved in ET. Similarly, measurements of nigral iron content and neuromelanin are unremarkable in most studies; this is in contrast to Parkinson's disease (PD). PET and MRS studies provide limited evidence for cerebellar and thalamic GABAergic dysfunction.

Conclusions: There is robust evidence indicating that the cerebellum plays a key role within a multiple oscillator tremor network which underlies tremor genesis. However, whether cerebellar dysfunction relies on a neurodegenerative process remains unclear. Dopaminergic and iron imaging do not suggest a substantial overlap of ET with PD pathophysiology. There is limited evidence for alterations of the GABAergic neurotransmitter system in ET. The clinical, demographical, and genetic heterogeneity of ET translates into neuroimaging and likely explains the various inconsistencies reported.
Fast Ripples as a Biomarker of Epileptogenic Tuber in Tuberous Sclerosis Complex Patients Using Stereo-Electroencephalograph
Authors: Wang Yangshuo , Yuan Liu , Zhang Shaohui , Liang Shuangshuang , Yu Xiaoman , Liu Tinghong , Yang Xiaofeng , Liang Shuli
Published: June 2021

Objectives: To evaluate the value of fast ripples (FRs) (200–500 Hz) recorded with stereo-electroencephalograph (SEEG) in the localization of epileptogenic tubers in patients with tuberous sclerosis complex (TSC).

Methods: Seventeen TSC patients who underwent preoperative SEEG examination and resective epilepsy surgery were retrospectively enrolled. They were divided into two groups according to the seizure control at 1-year postoperative follow-up. The occurrence frequencies of FRs were automatically counted, and the FR rate was calculated. The high FR rate was defined as FR rate ≧0.5. According to different positions, the contacts’ locations were divided into three groups: inner of the tubers, the junction region of the tubers, and out of the tubers. The influence factors of postoperative seizure freedom were also analyzed.

Results: Twelve patients reached postoperative seizure freedom at 1-year follow-up. In total, FRs were found in 24.2% of the contacts and 67.1% of the tubers in all assessed patients. There were 47 high FR rate contacts localized in the junction region of the tubers, which was 62.7% of the 75 high FR rate contacts in total and was 8.4% of the total 561 contacts localized in the junction region of the tubers. Total removal of epileptogenic tubers and total resection of the high FR rate tubers/contacts were associated with postoperative seizure freedom (P < 0.05).

Conclusion: FRs could be extensively detected in TSC patients using SEEG, and high FR rate contacts were mostly localized in the junction region of the epileptogenic tuber, which could aid in the localization of epileptogenic tubers.
Not as Bad as I Thought: Consumers' Positive Attitudes Toward Innovative Insect-Based Foods
Authors: Junges Juliana Rotunno , do Canto Natália Rohenkohl , de Barcellos Marcia Dutra
Published: June 2021

Considering that the demand for food will increase by 70% by 2050, consuming insect-based foods appears as a protein alternative due to their nutritional quality and low environmental impact. However, there is a need to investigate the acceptance of these innovative foods, especially in traditional meat-eating markets, such as in Southern Brazil (land of the Gauchos). The purpose of this manuscript is to analyze consumers' attitudes toward innovative insect-based foods. The methodological procedures were divided into two stages. In the qualitative stage, 14 interviews were conducted regarding meat consumption habits. In the quantitative stage, a survey was carried out with 433 consumers. A factor and cluster analysis were performed, and two different groups of consumers were found. The results clearly show a segment with positive attitudes toward insect-based foods. This group had a low degree of neophobia. The products were perceived as not tasty and disgusting, but they were considered modern, with high nutritional value, positive, safe, and beneficial to the environment. Appearance, price, and packaging, combined with flavor, proved to be the attributes considered by consumers as the most important for their acceptance.
The ETS Inhibitor YK-4-279 Suppresses Thyroid Cancer Progression Independent of TERT Promoter Mutations
Authors: Xue Junyu , Li Shiyong , Shi Peijie , Chen Mengke , Yu Shuang , Hong Shubin , Li Yanbing , Liu Rengyun , Xiao Haipeng
Published: June 2021

Hotspot mutations in the core promoter region of the telomerase reverse transcriptase (TERT) gene have been well established to associate with aggressive clinical characteristics, radioiodine refractory, tumor recurrence, and mortality in thyroid cancer. Several E-twenty-six (ETS) transcription factors were reported to selectively bound to the mutant TERT promoter and activated TERT expression. In this study we aimed to investigate whether TERT promoter mutations confer sensitivity to ETS inhibitor YK-4-279 in thyroid cancer cells and whether this inhibitor could be served as a potential therapeutic agent for thyroid cancer. In vitro assays showed that YK-4-279 treatment sharply suppressed cell viability, colony formation, migration, and invasion, as well as induced cell cycle arrest and apoptosis in a panel of thyroid cancer cells. The cell viability after YK-4-279 treatment was similar between cell lines harboring mutant and wild-type TERT promoters. Furthermore, YK-4-279 treatment reduced both luciferase activity and mRNA expression of TERT independent of TERT promoter mutation status. Data from RNA-seq further revealed that YK-4-279 significantly affected biological processes including DNA replication and cell cycle. Reduced DNA helicase activity and decreased expression of several helicase genes were observed after YK-4-279 treatment. Moreover, YK-4-279 significantly inhibited tumor growth and induced apoptosis in a xenograft mice model. Thus, ETS inhibitor YK-4-279 suppressed TERT expression and conferred anti-tumor activity in a TERT promoter mutation-independent manner, and it could be a potential agent for the treatment of advanced thyroid cancers.
A Schistosoma japonicum MicroRNA Exerts Antitumor Effects Through Inhibition of Both Cell Migration and Angiogenesis by Targeting PGAM1
Authors: Hu Chao , Li Yuzhen , Pan Danting , Wang Jing , Zhu Liufang , Lin Yu , Zhu Shanli , Pan Weiqing
Published: June 2021

MicroRNA (miRNA) is an important regulator for gene expression. Recent studies showed that some heterogenous miRNAs derived from both parasite and plant can regulate expression of mammalian gene in a cross-species or even a cross-kingdom manner. Here, we identified a Schistosoma japonicum miRNA (designated as sja-miR-61) that is present in the hepatocyte of mice infected with the parasite. The sja-miR-61 mimics significantly inhibited the migration of both mouse and human hepatoma cells in vitro. In a xenograft animal model, significant reductions of the tumor volume and weight were observed in mice inoculated with hepatoma cells transfected with sja-miR-61 mimics compared to the controls. We found that the in vivo inhibition of tumor growth was through its anti-angiogenesis activity. Mechanically, we identified the phosphoglycerate mutase 1 (PGAM1) gene as a target of sja-miR-61 and found that the sja-miR-61-mediated suppression of cell migration and anti-angiogenesis by cross-species down-regulation of PGAM1 expression. These data indicated that sja-miR-61 is a tumor suppressor miRNA that may have therapeutic potential for human cancers.
Targeting Immunometabolism in Glioblastoma
Authors: Mohan Aditya A. , Tomaszewski William H. , Haskell-Mendoza Aden P. , Hotchkiss Kelly M. , Singh Kirit , Reedy Jessica L. , Fecci Peter E. , Sampson John H. , Khasraw Mustafa
Published: June 2021

We have only recently begun to understand how cancer metabolism affects antitumor responses and immunotherapy outcomes. Certain immunometabolic targets have been actively pursued in other tumor types, however, glioblastoma research has been slow to exploit the therapeutic vulnerabilities of immunometabolism. In this review, we highlight the pathways that are most relevant to glioblastoma and focus on how these immunometabolic pathways influence tumor growth and immune suppression. We discuss hypoxia, glycolysis, tryptophan metabolism, arginine metabolism, 2-Hydroxyglutarate (2HG) metabolism, adenosine metabolism, and altered phospholipid metabolism, in order to provide an analysis and overview of the field of glioblastoma immunometabolism.
Echocardiographic Changes and Long-Term Clinical Outcomes in Pediatric Patients With Pulmonary Arterial Hypertension Treated With Bosentan for 72 Weeks: A Post-hoc Analysis From the FUTURE 3 Study
Authors: Beghetti Maurice , Berger Rolf M. F. , Bonnet Damien , Grill Simon , Lesage Catherine , Lemarie Jean-Christophe , Ivy D. Dunbar
Published: June 2021

FormUlation of bosenTan in pUlmonary arterial hypeRtEnsion (FUTURE) 3 was a 24-week open-label, prospective, and randomized phase 3 study that assessed the pharmacokinetics of bosentan 2 mg/kg b.i.d. or t.i.d. in children with pulmonary arterial hypertension (PAH). We report findings from a post-hoc analysis that explored the prognostic value of echocardiographic changes during FUTURE 3 in relation to clinical outcomes observed during the 24-week core study and 48-week extension. Patients aged ≥3 months to <12 years (n = 64) received oral doses of bosentan 2 mg/kg b.i.d. or t.i.d. (1:1) for 24 weeks, after which they were eligible to enter the extension with continued bosentan administration. Echocardiographic evaluations were performed at baseline, Week 12, and 24 of the core study via central reading, and analyzed post-hoc for correlation with clinical outcomes (time to PAH worsening, time to death, and vital status). Sixty-four patients were randomized in the core study [median (IQR) age 3.8 (1.7–7.8) years]; and 58 patients (90.6%) entered the 48-week extension. Most of the patients (68.8%) were receiving ≥1 PAH medication at baseline. Echocardiographic changes during the core study were small but with high variability. There were statistically significant associations at Week 24 between worsening of the parameters, systolic left ventricular eccentricity index (LVEIS) and E/A ratio mitral valve flow, and the outcomes of time to death and time to PAH worsening. Additional studies that utilize simple and reproducible echocardiographic assessments are needed to confirm these findings and subsequently identify potential treatment goals in pediatric PAH.
Maternal and Perinatal Determinants of Late Hospital Discharge Among Late Preterm Infants; A 5-Year Cross-Sectional Analysis
Authors: Khasawneh Wasim , Alyousef Rahaf , Akawi Zuhour , Al-Dhoon Areen , Odat Ahlam
Published: June 2021

Background: Although late preterm infants (LPIs) account for the majority of preterm births, they are mistakenly labelled and treated as “near term.” Whether longer initial hospital stay improves their outcomes and lowers readmission is controversial. The aim of this study is to identify maternal and perinatal factors associated with longer hospital stay and to assess the rate of readmission.

Methods: The medical records of LPIs delivered at an academic center in Jordan over a 5-year period were reviewed. They were divided according to their initial hospital stay into: Early discharge group (ED, ≤ 3 days) and late discharge group (LD, > 3 days). Maternal and perinatal factors associated with > 3-day hospital stay were reported. The rate of readmission was compared between both groups.

Results: 2236 LPIs were included in the analysis representing 13% of total births and 81% of premature births. LD group constituted 54%. A thousand two hundred forty three (56%) required admission to NICU. Factors associated with longer hospital stay included maternal prolonged rupture of membranes (AOR 1.9, 95% C.I 1.5, 2.4, p 0.000), C-section delivery (AOR 2.4, 95% C.I 1.9, 3, p 0.001), <35-week gestation (AOR 3.8, 95% C.I 2.6, 5, p 0.000), small-for-gestational age (AOR 1.9, 95% C.I 1.1, 3.8, p 0.03), birthweight <2,500 g (AOR 1.3, 95% C.I 1.1, 1.6, p 0.02), NICU admission (AOR 6.3, 95% C.I 3.4, 11.5, p 0.000), RDS (AOR 2.3, 95% C.I 1.5, 3.6, p 0.005), surfactant therapy (AOR 5, 95% C.I 1.9, 13.5, p 0.001), use of CPAP (AOR 1.7, 95% C.I 1.2, 2.2, p 0.001), jaundice (AOR 11.2, 95% C.I 7.7, 16.2, p 0.000), and sepsis (AOR 10.3, 95% C.I 4.8, 22, p 0.000). Readmission rate was 19% among the LD group and 13% among the ED group.

Conclusion: LPIs are at high risk for developing prematurity-related morbidities and the duration of their initial hospital stay can be anticipated based on certain predisposing maternal and perinatal factors. Late discharge of LPIs does not lower the rate of readmission.