bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19-Related Neuropsychiatric Symptoms in Patients With Alcohol Abuse Conditions During the SARS-CoV-2 Pandemic: A Retrospective Cohort Study Using Real World Data From Electronic Health Records of a Tertiary Hospital
Authors: Varela Rodríguez Carolina , Arias Horcajadas Francisco , Martín-Arriscado Arroba Cristina , Combarro Ripoll Carolina , Juanes Gonzalez Alba , Esperesate Pajares Marina , Rodrigo Holgado Irene , Cadenas Manceñido Álvaro , Sánchez Rodríguez Laura , Baselga Penalva Blanca , Marín Marta , Rubio Gabriel
Published: March 2021

Patients with an alcohol abuse disorder exhibit several medical characteristics and social determinants, which suggest a greater vulnerability to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a worse course of the coronavirus disease 2019 (COVID-19) once infected. During the first wave of the COVID-19, most of the countries have register an increase in alcohol consumption. However, studies on the impact of alcohol addiction on the risk of COVID-19 infection are very scarce and inconclusive. This research offers a descriptive observational retrospective cohort study using real world data obtained from the Electronic Health Records. We found that patients with a personal history of alcohol abuse were 8% more likely to extend their hospitalization length of stay for 1 day (95% CI = 1.04–1.12) and 15% more likely to extend their Intensive Care Unit (ICU) length of stay (95% CI = 1.01–1.30). They were also 5.47 times more at risk of needing an ICU admission (95% CI = 1.61–18.57) and 3.54 times (95% CI = 1.51–8.30) more at risk of needing a respirator. Regarding COVID-19 symptoms, patients with a personal history of alcohol abuse were 91% more likely of exhibiting dyspnea (95% CI = 1.03–3.55) and 3.15 times more at risk of showing at least one neuropsychiatric symptom (95% CI = 1.61–6.17). In addition, they showed statistically significant differences in the number of neuropsychiatric symptoms developed during the COVID-19 infection. Therefore, we strongly recommend to warn of the negative consequences of alcohol abuse over COVID-19 complications. For this purpose. Clinicians should systematically assess history of alcohol issues and drinking habits in all patients, especially for those who seek medical advice regarding COVID-19 infection, in order to predict its severity of symptoms and potential complications. Moreover, this information should be included, in a structured field, into the Electronic Health Record to facilitate the automatic extraction of data, in real time, useful to evaluate the decision-making process in a dynamic context.
Plinabulin, a Distinct Microtubule-Targeting Chemotherapy, Promotes M1-Like Macrophage Polarization and Anti-tumor Immunity
Authors: Natoli Marina , Herzig Petra , Pishali Bejestani Elham , Buchi Melanie , Ritschard Reto , Lloyd G. Kenneth , Mohanlal Ramon , Tonra James R. , Huang Lan , Heinzelmann Viola , Trüb Marta , Zippelius Alfred , Kashyap Abhishek S.
Published: March 2021

Reprogramming tumor infiltrating myeloid cells to elicit pro-inflammatory responses is an exciting therapeutic maneouver to improve anti-tumor responses. We recently demonstrated that a distinct microtubule-targeting drug, plinabulin—a clinical-stage novel agent—modulates dendritic cell maturation and enhances anti-tumor immunity. Here, we investigated the effects of plinabulin on macrophage polarizationin vitroandin vivo. Plinabulin monotherapy induced significant tumor growth inhibition in mice bearing subcutaneous MC38 colon cancer. Importantly, the regressing tumors were characterized by an increase in M1-like/M2-like tumor-associated macrophages (TAM) ratio. The efficacy of plinabulin remained unaltered in T cell-deficient Rag2−/−mice, suggesting an important role of macrophages in driving the drug's anti-tumor effect. Exposure of murine and healthy human macrophages to plinabulin induced polarization toward the M1 phenotype, including increased expression of co-stimulatory molecules CD80, CD86 and pro-inflammatory cytokines IL-1β, IL-6, and IL-12. M2-associated immunosuppressive cytokines IL-10 and IL-4 were reduced. This pro-inflammatory M1-like skewing of TAMs in response to plinabulin was dependent on the JNK pathway. Functionally, plinabulin-polarized human M1 macrophages directly killed HuT 78 tumor cellsin vitro. Importantly, plinabulin induced a functional M1-like polarization of tumor infiltrating macrophages in murine tumors as well as in tumor samples from ovarian cancer patients, by preferentially triggering M1 proliferation. Our study uncovers a novel immunomodulatory effect of plinabulin in directly triggering M1 polarization and proliferation as well as promoting TAM anti-tumoral effector functions.
CryptoKitties Transaction Network Analysis: The Rise and Fall of the First Blockchain Game Mania
Authors: Jiang Xin-Jian , Liu Xiao Fan
Published: March 2021

CryptoKitties was the first widely recognized blockchain game. Players could own, breed, and trade kitties, which are the only prop in the game. The game gained explosive growth upon its release but quickly collapsed in a short time. This study analyzes its entire player activity history for the first time in literature and tries to find the reasons for the rise and fall of this first blockchain game mania. First, we extracted the five million transaction records among 100 thousand addresses involved in CryptoKitties in the past three years. Based on the numbers of addresses involved in the game each day, we divide the game progress into four stages: the primer, the rise, the fall, and the serenity. We construct a temporal kitty ownership transfer network and analyze the varying network parameters in the four stages. We find that a large number of players poured in during the 10th and 18th days since the game release and quickly exited in the following month. Since then, a few big players have gradually dominated the game, concentrating the game resources. Through further analysis, we find that the main reason for the rapid increase in the game popularity was the increase of public attention by media outlets, while the reasons for the rapid decline in the game popularity include the oversupply of kitties, the decreasing of player income, a widening gap between the rich and poor players, and the limitations of blockchain systems. Based on these observations, we advise on the further blockchain game design: (1) to finely control the production of props and avoid an oversupply, (2) to balance the gaming cost and revenue and protect the enjoyment of players, (3) to narrow down the gap between rich and poor and create an equal gaming community, (4) to consider the limitations of blockchain systems in their game designs.
Impact of Different Daily Light Integrals and Carbon Dioxide Concentrations on the Growth, Morphology, and Production Efficiency of Tomato Seedlings
Authors: Huber Brandon M. , Louws Frank J. , Hernández Ricardo
Published: March 2021

Indoor growing systems with light-emitting diodes offer advantages for the growth of tomato seedlings through uniform and optimized environmental conditions which increase consistency between plants and growing cycles. CO2 enrichment has been shown to improve the yield of crops. Thus, this research aimed to characterize the effects of varied light intensities and CO2 enrichment on the growth, morphology, and production efficiency of tomato seedlings in indoor growing systems. Four tomato cultivars, “Florida-47 R,” “Rebelski,” “Maxifort,” and “Shin Cheong Gang,” were subjected to three different daily light integrals (DLIs) of 6.5, 9.7, and 13 mol m–2 d–1 with a percent photon flux ratio of 40 blue:60 red and an end-of-day far-red treatment of 5 mmol m–2 d–1. The plants were also subjected to three different CO2 concentrations: 448 ± 32 (400-ambient), 1010 ± 45 (1000), and 1568 ± 129 (1600) μmol mol–1. Temperature was maintained at 24.3°C ± 0.48/16.8°C ± 1.1 (day/dark; 22.4°C average) and relative humidity at 52.56 ± 8.2%. Plant density was 1000 plants m–2 until canopy closure. Morphological measurements were conducted daily to observe the growth response over time. In addition, data was collected to quantify the effects of each treatment. The results showed increases in growth rate with increases in the DLI and CO2 concentration. In addition, CO2 enrichment to 1000–1600 μmol mol–1 increased the light use efficiency (gDM mol–1applied) by 38–44%, and CO2 enrichment to 1600 μmol mol–1 did not result in any additional increase on shoot fresh mass, shoot dry mass, and stem extension. However, the net photosynthetic rate obtained with 1600 μmol mol–1 was 31 and 68% higher than those obtained with 1000 and 400 μmol mol–1, respectively. Furthermore, the comparison of the light and CO2 treatment combinations with the control (13 mol m–2 d–1–400CO2) revealed that the plants subjected to 6.5DLI–1600CO2, 9.7DLI–1000CO2, and 9.7DLI–1600CO2 treatment combinations exhibited the same growth rate as the control plants but with 25–50% less DLI. Furthermore, two treatment combinations (13.0DLI–1000CO2 and 13.0DLI–1600CO2) were associated with the consumption of comparable amount of energy but increased plant growth by 24–33%.
Retracing Storage Polysaccharide Evolution in Stramenopila
Authors: Chabi Malika , Leleu Marie , Fermont Léa , Colpaert Matthieu , Colleoni Christophe , Ball Steven G. , Cenci Ugo
Published: March 2021

Eukaryotes most often synthesize storage polysaccharides in the cytosol or vacuoles in the form of either alpha (glycogen/starch)- or beta-glucosidic (chrysolaminarins and paramylon) linked glucan polymers. In both cases, the glucose can be packed either in water-soluble (glycogen and chrysolaminarins) or solid crystalline (starch and paramylon) forms with different impacts, respectively, on the osmotic pressure, the glucose accessibility, and the amounts stored. Glycogen or starch accumulation appears universal in all free-living unikonts (metazoa, fungi, amoebozoa, etc.), as well as Archaeplastida and alveolata, while other lineages offer a more complex picture featuring both alpha- and beta-glucan accumulators. We now infer the distribution of these polymers in stramenopiles through the bioinformatic detection of their suspected metabolic pathways. Detailed phylogenetic analysis of key enzymes of these pathways correlated to the phylogeny of Stramenopila enables us to retrace the evolution of storage polysaccharide metabolism in this diverse group of organisms. The possible ancestral nature of glycogen metabolism in eukaryotes and the underlying source of its replacement by beta-glucans are discussed.
Emotional Creativity Improves Posttraumatic Growth and Mental Health During the COVID-19 Pandemic
Authors: Zhai Hong-Kun , Li Qiang , Hu Yue-Xin , Cui Yu-Xin , Wei Xiao-Wei , Zhou Xiang
Published: March 2021

Emotional creativity refers to a set of cognitive abilities and personality traits related to the originality of emotional experience and expression. Previous studies have found that emotional creativity can positively predict posttraumatic growth and mental health. The outbreak of coronavirus disease 2019 (COVID-19) has posed great challenges to people’s daily lives and their mental health status. Therefore, this study aims to address the following two questions: whether emotional creativity can improve posttraumatic growth and mental health during the COVID-19 pandemic and how it works. To do this, a multiple mediation model has been proposed, which supposes that emotional creativity is associated with posttraumatic growth and mental health through perceived social support and regulatory emotional self-efficacy. The study involved 423 participants from multiple regions with different COVID-19 involvement levels. Participants were asked to complete a questionnaire with six parts, which included Emotional Creativity Inventory (ECI), Regulatory Emotional Self-Efficacy Scale (RES), Stress-Related Growth Scale-Short Form (SRGS-SF), Multidimensional Scale of Perceived Social Support scale (MSPSS), Brief Symptom Inventory-18 scale (BSI-18), and COVID-19-related life events questionnaire. Path analysis used to examine the mediation model indicated that under the control of COVID-19-related life events and age, perceived social support mediated a positive association between emotional creativity and posttraumatic growth as well as a negative association between emotional creativity and all mental health problems, including somatization, depression, and anxiety. Regulatory emotional self-efficacy mediates the association between emotional creativity and posttraumatic growth, emotional creativity and anxiety, and emotional creativity and depression. The results suggest that emotional creativity plays an important role in coping with stressful events related to COVID-19. Furthermore, these results might provide a better understanding of the possible paths through which emotional creativity is related to psychological outcomes, such as mental health and posttraumatic growth.
Interaction of Serum Copper and Neurometabolites on Executive Dysfunction in Unmedicated Patients With Major Depressive Disorder
Authors: Liao Xiaoxiao , Lai Shunkai , Zhong Shuming , Wang Ying , Zhang Yiliang , Shen Shiyi , Huang Hui , Chen Guanmao , Chen Feng , Jia Yanbin
Published: March 2021

Objective: The mechanism of executive function (EF) impairment in major depressive disorder (MDD) remains unclear. Previous studies have demonstrated that altered serum copper levels and neurometabolic alterations may be associated with the psychopathology and cognitive impairment of MDD. While, their inter-relationships in MDD remain uncertain. The present study aims to assess whether the interaction between serum copper levels and neurometabolic alterations is involved in the deficit of executive function (EF) in patients with unmedicated MDD.

Methods: Serum copper levels and EFs were measured in 41 MDD patients and 50 control subjects. EFs were evaluated by Trail Making Test, Part-B (TMT-B), Digit Symbol Substitution Test (DSST), Wisconsin Card Sorting Task (WCST), and Semantic Verbal Fluency testing (SVFT). Additionally, 41 patients and 41 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) to obtain ratios of N-acetyl aspartate to creatine (NAA/Cr) and choline-containing compounds to creatine (Cho/Cr) in the lenticular nucleus (LN) of basal ganglia (BG). Finally, association and interaction analysis were conducted to investigate their inter-relationships.

Results: The results showed that patients performed worse in the DSST, WCST, TMT-B time and SVFT. Moreover, patients had higher serum copper levels, but lower NAA/Cr ratios in left LN of BG than healthy controls. In patients, serum copper levels were found to significantly negative associated with Categories Completed (CC) number of WCST (r = −0.408, p = 0.008), and positive associated with the Total Errors (TE) and Nonperseverative Errors (PE) number of WCST (r = 0.356, p = 0.023; r = −0.356, p = 0.022). In addition, the NAA/Cr ratios of left LN were found to significantly negative associated with VFS (r = −0.401, p = 0.009), as well as negative associated with serum copper levels (r = −0.365, p = 0.019). Finally, the interaction between copper and NAA may as influencing factors for SVFT and CC number of WCST in patients.

Conclusion: Our results indicated that the interaction of abnormal copper levels and NAA/Cr neurometabolic disruption of the LN may impact executive dysfunction, and this may relevant to the pathophysiology of executive impairment in MDD patients.
Treatment Response Prediction and Individualized Identification of Short-Term Abstinence Methamphetamine Dependence Using Brain Graph Metrics
Authors: Yan Cui , Yang Xuefei , Yang Ru , Yang Wenhan , Luo Jing , Tang Fei , Huang Sihong , Liu Jun
Published: March 2021

Background:The abuse of methamphetamine (MA) worldwide has gained international attention as the most rapidly growing illicit drug problem. The classification and treatment response prediction of MA addicts are thereby paramount, in order for effective treatments to be more targeted to individuals. However, there has been limited progress.

Methods:In the present study, 43 MA-dependent participants and 38 age- and gender-matched healthy controls were enrolled, and their resting-state functional magnetic resonance imaging data were collected. MA-dependent participants who showed 50% reduction in craving were defined as responders to treatment. The present study used the machine learning method, which is a support vector machine (SVM), to detect the most relevant features for discriminating and predicting the treatment response for MA-dependent participants based on the features extracted from the functional graph metrics.

Results:A classifier was able to differentiate MA-dependent subjects from normal controls, with a cross-validated prediction accuracy, sensitivity, and specificity of 73.2% [95% confidence interval (CI) = 71.23–74.17%), 66.05% (95% CI = 63.06–69.04%), and 80.35% (95% CI = 77.77–82.93%), respectively, at the individual level. The most accurate combination of classifier features included the nodal efficiency in the right middle temporal gyrus and the community index in the left precentral gyrus and cuneus. Between these two, the community index in the left precentral gyrus had the highest importance. In addition, the classification performance of the other classifier used to predict the treatment response of MA-dependent subjects had an accuracy, sensitivity, and specificity of 71.2% (95% CI = 69.28–73.12%), 86.75% (95% CI = 84.48–88.92%), and 55.65% (95% CI = 52.61–58.79%), respectively, at the individual level. Furthermore, the most accurate combination of classifier features included the nodal clustering coefficient in the right orbital part of the superior frontal gyrus, the nodal local efficiency in the right orbital part of the superior frontal gyrus, and the right triangular part of the inferior frontal gyrus and right temporal pole of middle temporal gyrus. Among these, the nodal local efficiency in the right temporal pole of the middle temporal gyrus had the highest feature importance.

Conclusion:The present study identified the most relevant features of MA addiction and treatment based on SVMs and the features extracted from the graph metrics and provided possible biomarkers to differentiate and predict the treatment response for MA-dependent patients. The brain regions involved in the best combinations should be given close attention during the treatment of MA.
Psychological Profiles of Chinese Patients With Hemodialysis During the Panic of Coronavirus Disease 2019
Authors: Yang Zhen-Hua , Pan Xiao-Ting , Chen Yu , Wang Lu , Chen Qiu-Xin , Zhu Yan , Zhu Yu-Jia , Chen Yong-Xi , Chen Xiao-Nong
Published: March 2021

Background: Hemodialysis patients not only suffer from somatic disorders but are also at high risks of psychiatric problems. Early this year, the outbreak of coronavirus disease 2019 (COVID-19) has caused great panic and anxiety worldwide. The impact of this acute public health event on the psychological status of hemodialysis patients and its relationship with their quality of life have not been fully investigated.

Methods: This study comprised two parts. The initial study enrolled maintenance hemodialysis patients treated in Ruijin Hospital for more than 3 months from March to May 2020 during the ongoing COVID-19 pandemic. Patients completed three questionnaires including the Impact of Events Scale–Revised (IES-R), General Health Questionnaire-28 (GHQ-28), and Kidney Disease Quality of Life (KDQOL) Short Form (SF). Follow-up study was performed from December 2020 to January 2021, when the pandemic of COVID-19 has been effectively contained in China. Only patients enrolled in the initial study were approached to participate in the follow-up study.

Results: There were 273 maintenance dialysis patients enrolled in the initial study and 247 finished the follow-up study. For the initial study, the estimated prevalence of nonspecific psychiatric morbidity was 45.8% (125/273) by GHQ-28. By IES-R, 53/273 (19.4%) patients presented with total scores above 24 that reflected clinical concerns. We found a significant difference regarding KDQOL scores between patients with different stress response (IES-R) groups (p = 0.026). Our follow-up study showed that KDQOL and SF-36 scores were significantly improved in comparison with those in the initial study (p = 0.006 and p = 0.031, respectively). Though total scores of GHQ-28 and IES-R did not change significantly, some subscales improved with statistical significance. Furthermore, gender, education background, and duration of hemodialysis were three factors that may affect patients' mental health, quality of life, or health status while dialysis duration was the only variable that correlated with those parameters. However, these correlations were combined effects of the COVID-19 pandemic and the dialysis itself.

Conclusions: We found a correlation between changes in the mental health status of dialysis patients and changes in their quality of life. These responses were also mediated by patients' psychosocial parameters. Our results urge the necessity of psychotherapeutic interventions for some patients during this event.
Baselining Flexibility from PV on the DSO-Aggregator Interface
Authors: Fonteijn Rik , Nguyen Phuong H. , Morren Johan , Slootweg J. G. (Han)
Published: March 2021

Flexibility can be used to mitigate distribution network overloading. Distribution system operators (DSOs) can obtain this flexibility from market parties connected to the distribution network. After flexibility has been delivered to the DSO, it needs to be settled. This is typically done by comparing load measurements with a baseline. This baseline describes an asset’s power profile in case no flexibility would have been delivered. Until recently, baselining research mainly focused on large-scale, predictable and controllable assets. The flexibility used by DSOs however typically comes from small-scale, less predictable and less controllable assets. This paper addresses the baselining problem for photo-voltaic systems. Three existing baselining methods are selected based on their simplicity and transparency and their limitations with respect to application towards photo-voltaic systems are evaluated. Based on this, a proof-of-concept for a new, fourth method is provided. It overcomes some of the limitations of the three existing ones, while still ensuring simplicity and transparency in order to promote market acceptance and practical applicability. All four methods are subjected to two different curtailment strategies: curtailing all peaks above a threshold and curtailing based on a day-ahead flexibility request. Using weather data from three summer weeks in 2019, it is shown that the newly developed method is able to provide a more accurate baseline than the existing methods.
Test-Retest and Minimal Detectable Change in the Assessment of Muscle Strength and Muscle Power in Upper and Lower Extremity Exercises in 9- to 14-Year-Old Children
Authors: Horta-Gim Mario , Romero-Pérez Ena , Medina-Pérez Carlos , Tánori-Tapia José , Núñez-Othón Gabriel , Novo André , de Paz José
Published: March 2021

The prescription of maximal dynamic strength training in both adults and children is based on the evaluation of maximum strength, usually by one-repetition maximum tests (1RM). This study examined the test-retest reliability and the minimal detectable change (MDC) of the maximal force test and muscle power test. Forty-eight children (9–14 years old) completed two test–retest sessions that involved a one-repetition maximum (1RM) test and a muscle power test for leg extension (LE) and seated bench press (SBP). The MDC values of the 1RM test in the LE and SBP tests ranged from 7.35 to 11.34 kg and 6.84 to 7.92 kg, respectively. The MDC values of the muscle power test in the LE and SBP ranged from 30.32 to 63.20 Watt and 22.65 to 29.53 Watt, respectively. In children 9 to 14 years old, the increase of maximum strength along the growth curve was different in each muscle group studied. The repeatability of the 1RM test of the SBP was excellent (ICC 0.974) and was better than that of the LE (ICC, 0.954). The MDC of the 1RM test evaluation was 19.56% in the LE and 12.93% in the SBP.
Finding Effective Item Assignment Plans with Weighted Item Associations Using A Hybrid Genetic Algorithm
Authors: Ryu Minho , Ahn Kwang-Il , Lee Kichun
Published: March 2021

By identifying useful relationships between massive datasets, association rule mining can provide new insights to decision-makers. Item assignment models based on association between items are used to place items in a retail or e-commerce environment to increase sales. However, existing models fail to combine these associations with item-specific information, such as profit and purchasing frequency. To find effective assignments with item-specific information, we propose a new hybrid genetic algorithm that incorporates a robust tabu search with a novel rectangular partially matched crossover, focusing on rectangular layouts. Interestingly, we show that our item assignment model is equivalent to popular quadratic assignment NP-hard problems. We show the effectiveness of the proposed algorithm, using benchmark instances from QAPLIB and synthetic databases that represent real-life retail situations, and compare our algorithm with other existing algorithms. We also show that the proposed crossover operator outperforms a few existing ones in both fitness values and search times. The experimental results show that not only does the proposed item assignment model generates a more profitable assignment plan than the other tested models based on association alone but it also obtains better solutions than the other tested algorithms.
Differences and Similarities in Predictors of Expressive Vocabulary Development between Children with Down Syndrome and Young Typically Developing Children
Authors: Næss Kari-Anne B. , Ostad Johanne , Nygaard Egil
Published: March 2021

The purpose of this study was to examine potential differences in the predictors of expressive vocabulary development between children with Down syndrome and typically developing children to support preparation for intervention development. An age cohort of 43 children with Down syndrome and 57 typically developing children with similar nonverbal mental age levels were assessed at three time points. Linear mixed models were used to investigate the predictors of expressive vocabulary over time. Both groups achieved progress in expressive vocabulary. The typically developing children had steeper growth than the children with Down syndrome (1.38 SD vs. 0.8 SD, p < 0.001). In both groups, receptive vocabulary, auditory memory, and the home literacy environment were significant predictors of development. In the children with Down syndrome, the phonological awareness and oral motor skills were also significant. Group comparisons showed that receptive vocabulary, auditory memory and oral motor skills were stronger predictors in the children with Down syndrome than in the typically developing children. These results indicate that children with Down syndrome are more vulnerable when it comes to risk factors that are known to influence expressive vocabulary than typically developing children. Children with Down syndrome therefore require early broad-based expressive vocabulary interventions.
Eye-Tracking Training Improves Inhibitory Control in Children with Attention-Deficit/Hyperactivity Disorder
Authors: Lee Tsz , Yeung Michael , Sze Sophia , Chan Agnes
Published: March 2021

Disinhibition is a common sign among children with attention-deficit/hyperactivity disorder (ADHD). The present study examined the effect of computerized eye-tracking training to improve inhibitory control in ADHD children. Thirty-two ADHD children (mean age = 8.4 years) were recruited. Half of the participants underwent 240 min of eye-tracking training over two weeks (i.e., experimental group), while the other half did not receive any training (i.e., control group). After training, the experimental group exhibited significant improvements in neuropsychological tests of inhibition, such as faster reaction time in the incongruent condition of the Flanker test, more unique designs in the Category Fluency and Five-Point Tests, and a faster completion time in Trail 2 of the Children’s Color Trail Test. The control group did not show significant changes in any of these tests. Our findings support the use of eye-tracking training to improve the inhibitory control of ADHD children.
Safinamide Improves Non-Motor Symptoms Burden in Parkinson’s Disease: An Open-Label Prospective Study
Authors: Santos García Diego , Labandeira Guerra Carmen , Yáñez Baña Rosa , Cimas Hernando Maria Icíar , Cabo López Iria , Paz Gonález Jose Manuel , Alonso Losada Maria Gemma , González Palmás María José , Martínez Miró Cristina
Published: March 2021

Some studies observed a benefit of Parkinson’s disease (PD) patients after treatment with safinamide in some non-motor symptoms (NMSs). The aim of this study was to analyze the effectiveness of safinamide on NMS burden in PD. SAFINONMOTOR (an open-label study of the effectiveness of safinamide on non-motor symptoms in Parkinson’s disease patients) is a prospective open-label single-arm study conducted in five centers from Spain. The primary efficacy outcome was the change from baseline (V1) to the end of the observational period (6 months) (V4) in the non-motor symptoms scale (NMSS) total score. Between May/2019 and February/2020 50 patients were included (age 68.5 ± 9.12 years; 58% females; 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The NMSS total score was reduced by 38.5% (from 97.5 ± 43.7 in V1 to 59.9 ± 35.5 in V4; p < 0.0001). By domains, improvement was observed in sleep/fatigue (−35.8%; p = 0.002), mood/apathy (−57.9%; p < 0.0001), attention/memory (−23.9%; p = 0.026), gastrointestinal symptoms (−33%; p = 0.010), urinary symptoms (−28.3%; p = 0.003), and pain/miscellaneous (−43%; p < 0.0001). Quality of life (QoL) also improved with a 29.4% reduction in the PDQ-39SI (from 30.1 ± 17.6 in V1 to 21.2 ± 13.5 in V4; p < 0.0001). A total of 21 adverse events in 16 patients (32%) were reported, 5 of which were severe (not related to safinamide). Dyskinesias and nausea were the most frequent (6%). Safinamide is well tolerated and improves NMS burden and QoL in PD patients with severe or very severe NMS burden at 6 months.
The Effect of Centralized Financial and Social Incentives on Cooperative Behavior and Its Underlying Neural Mechanisms
Authors: Micheli Leticia , Stallen Mirre , Sanfey Alan G.
Published: March 2021

Incentives are frequently used by governments and employers to encourage cooperation. Here, we investigated the effect of centralized incentives on cooperation, firstly in a behavioral study and then replicated in a subsequent neuroimaging (fMRI) study. In both studies, participants completed a novel version of the Public Goods Game, including experimental conditions in which the administration of centralized incentives was probabilistic and incentives were either of a financial or social nature. Behavioral results showed that the prospect of potentially receiving financial and social incentives significantly increased cooperation, with financial incentives yielding the strongest effect. Neuroimaging results showed that activation in the bilateral lateral orbitofrontal cortex and precuneus increased when participants were informed that incentives would be absent versus when they were present. Furthermore, activation in the medial orbitofrontal cortex increased when participants would potentially receive a social versus a financial incentive. These results speak to the efficacy of different types of centralized incentives in increasing cooperative behavior, and they show that incentives directly impact the neural mechanisms underlying cooperation.
Long-Term Incidence of Advanced Colorectal Neoplasia in Patients with Serrated Polyposis Syndrome: Experience in a Single Academic Centre
Authors: Rodríguez-Alcalde Daniel , Castillo-López Guillermo , López-Vicente Jorge , Hernández Luis , Lumbreras-Cabrera Mercedes , Moreno-Sánchez Diego
Published: March 2021

Serrated polyposis syndrome (SPS) implies a slightly elevated risk of colorectal cancer (CRC) during endoscopic follow-up, but its natural course is still not well known. The main objective of this study was to describe the long-term risk of developing advanced neoplasia (AN) in these patients. Until October 2020, individuals who fulfilled 2010 WHO criteria I and/or III for SPS were retrospectively recruited. We selected those under endoscopic surveillance after resection of all lesions >3 mm in a high-quality colonoscopy. We excluded patients with total colectomy at diagnosis and those with any interval between colonoscopies >3.5 years. We defined AN as advanced serrated polyp (≥10 mm and/or with dysplasia), advanced adenoma, or CRC. In 109 patients, 342 colonoscopies were performed (median = 3, median interval = 1.8 years) during a median follow-up after colonic clearance of 5.0 years. Five-year cumulative incidences of AN were 21.6% globally, and 5.6%, 10.8%, and 50.8% in patients who fulfilled criterion I, III, and both, respectively (p < 0.001). No CRC was diagnosed and only 1 (0.9%) patient underwent surgery. In conclusion, cumulative incidences of AN could be lower than previously described, at least in patients who fulfil the 2010 WHO criterion III alone. Therefore, low-risk individuals might benefit from less stringent surveillance.
Dive into Single, Seek Out Multiple: Probing Cancer Metastases via Single-Cell Sequencing and Imaging Techniques
Authors: Su Shang , Li Xiaohong
Published: March 2021

Metastasis is the cause of most cancer deaths and continues to be the biggest challenge in clinical practice and laboratory investigation. The challenge is largely due to the intrinsic heterogeneity of primary and metastatic tumor populations and the complex interactions among cancer cells and cells in the tumor microenvironment. Therefore, it is important to determine the genotype and phenotype of individual cells so that the metastasis-driving events can be precisely identified, understood, and targeted in future therapies. Single-cell sequencing techniques have allowed the direct comparison of the genomic and transcriptomic changes among different stages of metastatic samples. Single-cell imaging approaches have enabled the live visualization of the heterogeneous behaviors of malignant and non-malignant cells in the tumor microenvironment. By applying these technologies, we are achieving a spatiotemporal precision understanding of cancer metastases and clinical therapeutic translations.
Effect of Reducing Ataxia-Telangiectasia Mutated (ATM) in Experimental Autosomal Dominant Polycystic Kidney Disease
Authors: Zhang Jennifer Q. J. , Saravanabavan Sayanthooran , Rangan Gopala K.
Published: March 2021

The DNA damage response (DDR) pathway is upregulated in autosomal dominant polycystic kidney disease (ADPKD) but its functional role is not known. The ataxia-telangiectasia mutated (ATM) and AT and Rad3-related (ATR) protein kinases are key proximal transducers of the DDR. This study hypothesized that reducing either ATM or ATR attenuates kidney cyst formation and growth in experimental ADPKD. In vitro, pharmacological ATM inhibition by AZD0156 reduced three-dimensional cyst growth in MDCK and human ADPKD cells by up to 4.4- and 4.1-fold, respectively. In contrast, the ATR inhibitor, VE-821, reduced in vitro MDCK cyst growth but caused dysplastic changes. In vivo, treatment with AZD0156 by oral gavage for 10 days reduced renal cell proliferation and increased p53 expression in Pkd1RC/RC mice (a murine genetic ortholog of ADPKD). However, the progression of cystic kidney disease in Pkd1RC/RC mice was not altered by genetic ablation of ATM from birth, in either heterozygous (Pkd1RC/RC/Atm+/−) or homozygous (Pkd1RC/RC/Atm−/−) mutant mice at 3 months. In conclusion, despite short-term effects on reducing renal cell proliferation, chronic progression was not altered by reducing ATM in vivo, suggesting that this DDR kinase is dispensable for kidney cyst formation in ADPKD.
Serum Extracellular Vesicle-Derived miRNAs in Patients with Non-Small Cell Lung Cancer—Search for Non-Invasive Diagnostic Biomarkers
Authors: Kryczka Jolanta , Migdalska-Sęk Monika , Kordiak Jacek , Kiszałkiewicz Justyna M. , Pastuszak-Lewandoska Dorota , Antczak Adam , Brzeziańska-Lasota Ewa
Published: March 2021

The aim of the study was a search for diagnostic and/or prognostic biomarkers in patients with non-small cell lung cancer (NSCLC) patients, based on circulating microRNAs (miRs: miR-23a, miR-361, miR-1228 and miR-let7i) in extracellular vesicles (EVs). Serum EVs were isolated from NSCLC patients (n = 31) and control subjects (n = 21). RNA was isolated from EVs and reverse transcription reaction was performed. Relative levels of miR-23a, miR-361, miR-1228 and miR-let7i were assessed in real-time qPCR using TaqMan probes. Analysis was based on the 2-ΔΔCT method. Statistically significant lower levels of miR-23a and miR-let7i were observed among NSCLC patients vs. control group: miR-23a, 0.054 vs. 0.107; miR-let7i, 0.193 vs. 0.369 (p = 0.003, p = 0.005, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential of each individual serum EV-derived miRNA with an area under the curve AUC = 0.744 for miR-23a (p = 0.0003), 0.733 for miR-let7i (p = 0.0007). The decreased level of miR-23a in patients correlated with metastasis to lymph nodes and with AJCC tumor staging system. The results demonstrate that miR-23a and miR-let7i may prove clinically useful as significant, non-invasive markers in NSCLC diagnosis. Additionally, changing profile level of miR-23a that correlates with cancer development may be considered as an NSCLC progression marker.
Low Voltage Ride Through Controller for a Multi-Machine Power System Using a Unified Interphase Power Controller
Authors: Majlesi Atoosa , Miveh Mohammad Reza , Ghadimi Ali Asghar , Kalam Akhtar
Published: March 2021

In recent years, grid-connected photovoltaic (PV) power generations have become the most extensively used energy resource among other types of renewable energies. Increasing integration of PV sources into the power network and their dynamic performances under fault conditions is an important issue for grid code requirements. In this paper, a PV source as a unified interphase power controller (UIPC) is used to enhance the low voltage ride through (LVRT) and transient stability of a multi-machine power system. The suggested PV-based UIPC consists of two series voltage inverters and a parallel inverter. The UIPC injects the required active and reactive power to prevent voltage drop under grid fault conditions. Accordingly, a dynamic control system is designed based on proportional-integral (PI) controllers for the PV-based UIPC to operate in both normal and fault conditions. Simulations are done using Matlab/Simulink software, and the performance of the PV-based UIPC is compared with the conventional unified power flow controller (UPFC). The results of this study indicate the more favorable impact of the PV-based UIPC on the system compared to UPFC in improving LVRT capabilities and transient stability.
Drainage and Stand Growth Response in Peatland Forests—Description, Testing, and Application of Mechanistic Peatland Simulator SUSI
Authors: Laurén Ari , Palviainen Marjo , Launiainen Samuli , Leppä Kersti , Stenberg Leena , Urzainki Iñaki , Nieminen Mika , Laiho Raija , Hökkä Hannu
Published: March 2021

Drainage is an essential prerequisite in peatland forest management, which generally, but not always, increases stand growth. Growth response depends on weather conditions, stand and site characteristics, management and biogeochemical processes. We constructed a SUSI-simulator (SUoSImulaattori, in Finnish), which describes hydrology, stand growth and nutrient availability under different management, site types and weather conditions. In the model development and sensitivity analysis, we used water table (WT) and stand growth data from 11 Scots pine stands. The simulator was validated against a larger dataset collected from boreal drained peatlands in Finland. In validation, SUSI was shown to predict WT and stand growth well. Stand growth was mainly limited by inadequate potassium supply, and in Sphagnum peats by low oxygen availability. Model application was demonstrated for ditch network maintenance (DNM) by comparing stand growth with shallow (−0.3 m) and deep ditches (−0.9 m): The growth responses varied between 0.5 and 3.5 m3 ha−1 in five years, which is comparable to experimental results. SUSI can promote sustainable peatland management and help in avoiding unnecessary drainage operations and associated environmental effects, such as increased carbon emissions, peat subsidence, and nutrient leaching. The source code is publicly available, and the modular structure allows model extension to cost–benefit analyses and nutrient export to water courses.
Magnetic Helicity and the Geodynamo
Authors: Shebalin John V.
Published: March 2021

We present theoretical and computational results in magnetohydrodynamic turbulence that we feel are essential to understanding the geodynamo. These results are based on a mathematical model that focuses on magnetohydrodynamic (MHD) turbulence, but ignores compressibility and thermal effects, as well as imposing model-dependent boundary conditions. A principal finding is that when a turbulent magnetofluid is in quasi-equilibrium, the magnetic energy in the internal dipole component is equal to the magnetic helicity multiplied by the dipole wavenumber. In the case of the Earth, measurement of the exterior magnetic field gives us, through boundary conditions, the internal poloidal magnetic field. The connection between magnetic helicity and dipole field in the liquid core then gives us the toroidal part of the internal dipole field and a model value of 3 mT for the average core dipole magnetic field. Here, we present the theoretical analysis and numerical simulations that lead to these conclusions. We also test an earlier assertion that differential oblateness may be related to dipole alignment, and while there is an effect, rotation appears to be far more important. In addition, the relationship between dipole quasi-stationarity, broken ergodicity and broken symmetry is clarified. Lastly, we discuss how inertial waves in a rotating magnetofluid can affect dipole alignment.
Neuromodulation of Astrocytic K+ Clearance
Authors: Bellot-Saez Alba , Stevenson Rebecca , Kékesi Orsolya , Samokhina Evgeniia , Ben-Abu Yuval , Morley John W. , Buskila Yossi
Published: March 2021

Potassium homeostasis is fundamental for brain function. Therefore, effective removal of excessive K+ from the synaptic cleft during neuronal activity is paramount. Astrocytes play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]o) or impairments of the astrocytic clearance mechanism affect the resonance and oscillatory behavior of both the individual and networks of neurons. These results indicate that astrocytes have the potential to modulate neuronal network activity, however, the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behavior, on the astrocytic clearance process. Our results suggest that while some neuromodulators (5-HT; NA) might affect astrocytic spatial buffering via gap-junctions, others (DA; Histamine) primarily affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to maximize the synchronous network activity.
Potential Distribution of Aedes (Ochlerotatus) scapularis (Diptera: Culicidae): A Vector Mosquito New to the Florida Peninsula
Authors: Campbell Lindsay P. , Burkett-Cadena Nathan D. , Miqueli Evaristo , Unlu Isik , Sloyer Kristin E. , Medina Johana , Vasquez Chalmers , Petrie William , Reeves Lawrence E.
Published: March 2021

Aedes scapularis is a neotropical mosquito known to transmit pathogens of medical and veterinary importance. Its recent establishment in southeastern Florida has potential public health implications. We used an ecological niche modeling approach to predict the abiotic environmental suitability for Ae. scapularis across much of the Americas and Caribbean Islands. Georeferenced occurrence data obtained from the Global Biodiversity Inventory Facility and recent collection records of Ae. scapularis from southern Florida served as input for model calibration. Environmental layers included bioclimatic variables provided in 2000 to 2010 average Modern Era Retrospective-analysis for Research and Applications climatic (MERRAclim) data. Models were run in the software program Maxent. Isothermality values often found in costal environments, had the greatest contribution to model performance. Model projections suggested that there are areas predicted to be suitable for Ae. Scapularis across portions of the Amazon Basin, the Yucatán Peninsula, the Florida Peninsula, and multiple Caribbean Islands. Additionally, model predictions suggested connectivity of highly suitable or relatively suitable environments spanning the United States Gulf Coast, which may facilitate the geographic expansion of this species. At least sixteen Florida counties were predicted to be highly suitable for Ae. scapularis, suggesting that vigilance is needed by vector control and public health agencies to recognize the further spread of this vector.
Efficacy and Safety of Tranexamic Acid in Emergency Trauma: A Systematic Review and Meta-Analysis
Authors: Al-Jeabory Mahdi , Szarpak Lukasz , Attila Kecskes , Simpson Michael , Smereka Adam , Gasecka Aleksandra , Wieczorek Wojciech , Pruc Michal , Koselak Maciej , Gawel Wladyslaw , Checinski Igor , Jaguszewski Milosz J. , Filipiak Krzysztof J.
Published: March 2021

In trauma patients, bleeding can lead to coagulopathy, hemorrhagic shock, and multiorgan failure, and therefore is of fundamental significance in regard to early morbidity. We conducted a meta-analysis to evaluate the efficacy and safety of tranexamic acid (TXA) in civil and military settings and its impact on in-hospital mortality (survival to hospital discharge or 30-day survival), intensive care unit and hospital length of stay, incidence of adverse events (myocardial infarct and neurological complications), and volume of blood product transfusion. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic review of the literature using PubMed, Scopus, EMBASE, Web of Science, and the Cochrane Central Register and Controlled Trials (CENTRAL) database was conducted from inception to 10 January 2021. In-hospital mortality was reported in 14 studies and was 15.5% for the TXA group as compared with 16.4% for the non-TXA group (OR = 0.81, 95% CI 0.62–1.06, I2 = 83%, p = 0.12). In a civilian TXA application, in-hospital mortality in the TXA and non-TXA groups amounted to 15.0% and 17.1%, respectively (OR = 0.69, 95% CI 0.51–0.93, p = 0.02, I2 = 78%). A subgroup analysis of the randomized control trial (RCT) studies showed a statistically significant reduction in in-hospital mortality in the TXA group (14.3%) as compared with the non-TXA group (15.7%, OR = 0.89, 95% CI 0.83–0.96, p = 0.003, I2 = 0%). To summarize, TXA used in civilian application reduces in-hospital mortality. Application of TXA is beneficial for severely injured patients who undergoing shock and require massive blood transfusions. Patients who undergo treatment with TXA should be monitored for clinical signs of thromboembolism, since TXA is a standalone risk factor of a thromboembolic event and the D-dimers in traumatic patients are almost always elevated.