bluuebunny/crossref_metadata_2025 huggingface dataset:
TMP- SSurface2: A Novel Deep Learning-Based Surface Accessibility Predictor for Transmembrane Protein Sequence
Authors: Liu Zhe , Gong Yingli , Guo Yuanzhao , Zhang Xiao , Lu Chang , Zhang Li , Wang Han
Published: March 2021

Transmembrane protein (TMP) is an important type of membrane protein that is involved in various biological membranes related biological processes. As major drug targets, TMPs’ surfaces are highly concerned to form the structural biases of their material-bindings for drugs or other biological molecules. However, the quantity of determinate TMP structures is still far less than the requirements, while artificial intelligence technologies provide a promising approach to accurately identify the TMP surfaces, merely depending on their sequences without any feature-engineering. For this purpose, we present an updated TMP surface residue predictor TMP-SSurface2 which achieved an even higher prediction accuracy compared to our previous version. The method uses an attention-enhanced Bidirectional Long Short Term Memory (BiLSTM) network, benefiting from its efficient learning capability, some useful latent information is abstracted from protein sequences, thus improving the Pearson correlation coefficients (CC) value performance of the old version from 0.58 to 0.66 on an independent test dataset. The results demonstrate that TMP-SSurface2 is efficient in predicting the surface of transmembrane proteins, representing new progress in transmembrane protein structure modeling based on primary sequences. TMP-SSurface2 is freely accessible at https://github.com/NENUBioCompute/TMP-SSurface-2.0.
Association of a Network of Immunologic Response and Clinical Features With the Functional Recovery From Crotalinae Snakebite Envenoming
Authors: Gerardo Charles J. , Silvius Elizabeth , Schobel Seth , Eppensteiner John C. , McGowan Lauren M. , Elster Eric A. , Kirk Allan D. , Limkakeng Alexander T.
Published: March 2021

Background

The immunologic pathways activated during snakebite envenoming (SBE) are poorly described, and their association with recovery is unclear. The immunologic response in SBE could inform a prognostic model to predict recovery. The purpose of this study was to develop pre- and post-antivenom prognostic models comprised of clinical features and immunologic cytokine data that are associated with recovery from SBE.

Materials and Methods

We performed a prospective cohort study in an academic medical center emergency department. We enrolled consecutive patients with Crotalinae SBE and obtained serum samples based on previously described criteria for the Surgical Critical Care Initiative (SC2i)(ClinicalTrials.gov Identifier: NCT02182180). We assessed a standard set of clinical variables and measured 35 unique cytokines using Luminex Cytokine 35-Plex Human Panel pre- and post-antivenom administration. The Patient-Specific Functional Scale (PSFS), a well-validated patient-reported outcome of functional recovery, was assessed at 0, 7, 14, 21 and 28 days and the area under the patient curve (PSFS AUPC) determined. We performed Bayesian Belief Network (BBN) modeling to represent relationships with a diagram composed of nodes and arcs. Each node represents a cytokine or clinical feature and each arc represents a joint-probability distribution (JPD).

Results

Twenty-eight SBE patients were enrolled. Preliminary results from 24 patients with clinical data, 9 patients with pre-antivenom and 11 patients with post-antivenom cytokine data are presented. The group was mostly female (82%) with a mean age of 38.1 (SD ± 9.8) years. In the pre-antivenom model, the variables most closely associated with the PSFS AUPC are predominantly clinical features. In the post-antivenom model, cytokines are more fully incorporated into the model. The variables most closely associated with the PSFS AUPC are age, antihistamines, white blood cell count (WBC), HGF, CCL5 and VEGF. The most influential variables are age, antihistamines and EGF. Both the pre- and post-antivenom models perform well with AUCs of 0.87 and 0.90 respectively.

Discussion

Pre- and post-antivenom networks of cytokines and clinical features were associated with functional recovery measured by the PSFS AUPC over 28 days. With additional data, we can identify prognostic models using immunologic and clinical variables to predict recovery from SBE.
Mesenchymal Stromal Cell Derived Membrane Particles Are Internalized by Macrophages and Endothelial Cells Through Receptor-Mediated Endocytosis and Phagocytosis
Authors: da Costa Gonçalves Fabiany , Korevaar Sander S. , Ortiz Virumbrales Maitane , Baan Carla C. , Reinders Marlies E. J. , Merino Ana , Lombardo Eleuterio , Hoogduijn Martin J.
Published: March 2021

Mesenchymal stromal cells (MSC) are a promising therapy for inflammatory diseases. However, MSC are large and become trapped in the lungs after intravenous infusion, where they have a short survival time. To steer MSC immunoregulatory therapy beyond the lungs, we generated nm-sized particles from MSC membranes (membrane particles, MP), which have immunomodulatory properties, and investigated their internalization and mode of interaction in macrophages subtypes and human umbilical vein endothelial cells (HUVEC) under control and inflammatory conditions. We found that macrophages and HUVEC take up MP in a dose, time, and temperature-dependent manner. Specific inhibitors for endocytotic pathways revealed that MP internalization depends on heparan sulfate proteoglycan-, dynamin-, and clathrin-mediated endocytosis but does not involve caveolin-mediated endocytosis. MP uptake also involved the actin cytoskeleton and phosphoinositide 3-kinase, which are implicated in macropinocytosis and phagocytosis. Anti-inflammatory M2 macrophages take up more MP than pro-inflammatory M1 macrophages. In contrast, inflammatory conditions did not affect the MP uptake by HUVEC. Moreover, MP induced both anti- and pro-inflammatory responses in macrophages and HUVEC by affecting gene expression and cell surface proteins. Our findings on the mechanisms of uptake of MP under different conditions help the development of target-cell specific MP therapy to modulate immune responses.
Assessing Population-Level Effects of Anthropogenic Disturbance on a Marine Mammal Population
Authors: Dunlop Rebecca A. , Braithwaite Janelle , Mortensen Lars O. , Harris Catriona M.
Published: March 2021

The Population Consequences of Disturbance (PCoD) model is a conceptual framework used to assess the potential for population-level consequences following exposure of animals to a disturbance activity or stressor. This framework is a four-step process, progressing from changes in individual behavior and/or physiology, to changes in individual health, then vital rates, and finally to population-level effects. Despite its simplicity, there are few complete PCoD models available for any marine mammal species due to a lack of data available to parameterize many of the steps. Here, we present an application of the PCoD framework for migrating humpback whales exposed to a simulated commercial seismic survey scenario. We approached the framework in two ways; first, progressing sequentially forwards through the steps and basing our assessment on lactating females. This cohort was considered to be the most vulnerable in terms of energetic costs of disturbance, and most likely to influence any change in population growth due to future breeding success. Field measurements of behavioral responses of migrating humpback whales to seismic air guns from a previous study were used to parameterize an agent-based model (ABM). This ABM was used to estimate the probability of response, where a response was defined as a change in the migratory movement of female-calf pairs, and the duration of any resulting delay in migration. We then estimated the energetic consequences of any delay in migration for the lactating females and created population growth models with which to assess any population-level effects. The results of the forwards approach suggested a low potential for population consequences of seismic surveys on migrating humpbacks. Working backwards through the framework, we investigated “worst case” scenarios that could potentially lead to a population-level effect. Here, we started with increasing calf mortality and assumed that an exposure time greater than 48 h would increase mortality risk. We determined the most likely context in which this exposure would occur (resting area) and then tested this context within an ABM. This backwards approach illustrates how the PCoD model can be used to make management decisions regarding animal populations and exposure to anthropogenic stressors.
Review on Blue Perovskite Light-Emitting Diodes: Recent Advances and Future Prospects
Authors: Ge Chuangye , Fang Qianru , Lin Haoran , Hu Hanlin
Published: March 2021

Perovskite-based light-emitting diodes (PLEDs) have emerged as a promising alternative owning to the excellent optoelectronic properties including narrow emission linewidths, high photoluminescence quantum yield (PLQY), tunable emission wavelength, and high color purity. Over the past several years, significant progress has been obtained for green, red, and near-infrared PLEDs with a high external quantum efficiency (EQE) of over 20%. However, the development of blue PLEDs has been limited by several technical issues including poor film quality, inefficient device structure, higher trap density, and so on. To overcome these drawbacks with improved PLQY and EQE, we summarize and analyze the recent advances towards the development of three dimensional (3D), two dimensional (2D) and quasi-2D perovskites film employing composition and/or dimensional engineering. Moreover, the utilization of perovskite nanocrystals (PNCs) is also considered as a feasible strategy for the realization of high-performance blue PLEDs. We systematically evaluate the performance of sky-blue, pure-blue and deep blue PLEDs based on different perovskite materials. Finally, future prospective are proposed to promote the development of efficient blue PLEDs.
Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment
Authors: Yang Jinpu , Zhou Xinxin , Liu Xiaosun , Ling Zongxin , Ji Feng
Published: March 2021

The development of sequencing technology has expanded our knowledge of the human gastric microbiome, which is now known to play a critical role in the maintenance of homeostasis, while alterations in microbial community composition can promote the development of gastric diseases. Recently, carcinogenic effects of gastric microbiome have received increased attention. Gastric cancer (GC) is one of the most common malignancies worldwide with a high mortality rate. Helicobacter pylori is a well-recognized risk factor for GC. More than half of the global population is infected with H. pylori, which can modulate the acidity of the stomach to alter the gastric microbiome profile, leading to H. pylori-associated diseases. Moreover, there is increasing evidence that bacteria other than H. pylori and their metabolites also contribute to gastric carcinogenesis. Therefore, clarifying the contribution of the gastric microbiome to the development and progression of GC can lead to improvements in prevention, diagnosis, and treatment. In this review, we discuss the current state of knowledge regarding changes in the microbial composition of the stomach caused by H. pylori infection, the carcinogenic effects of H. pylori and non-H. pylori bacteria in GC, as well as the potential therapeutic role of gastric microbiome in H. pylori infection and GC.
Lipidomic Perturbations in Cynomolgus Monkeys are Regulated by Thyroid Stimulating Hormone
Authors: Xu Tao , Yang Yanling , Huang Xing , Ren Jianhong , Xu Ting , Xie Wei
Published: March 2021

Thyroid disease affects an estimated 200 million people worldwide, and is commonly associated with increased blood lipid levels. However, the mechanism by which thyroid-stimulating hormone (TSH) affects lipid profiles is not clear. Twenty-four cynomolgus monkeys were treated with a novel exogenous recombinant human TSH (rhTSH) (SNA001) at 9 μg kg−1, 22 μg kg−1, or 54 μg kg−1, and reference rhTSH (Thyrogen®) at 22 μg kg−1. The primary TSH (SNA001) pharmacokinetic (PK) parameters increased in a dose-dependent manner across the dose range of 9 μg kg−1, 22 μg kg−1, or 54 μg kg−1. Peak triiodothyronine (T3) and thyroxine (T4) levels were reached within 24 h after rhTSH administration, which was delayed by approximately 20 h. In total, 420 lipid species were detected and quantified by ultra-performance liquid chromatography high resolution spectrometry (UPLC-HR-MS)-based lipidomics. Notably, peak levels of lipid accumulation, particularly sphingomyelin (SM) and triglycerides (TG), appeared at 4 and 24 h, which was consistent with the pattern of TSH and T3/T4 levels, respectively. According to weighted correlation network analysis (WGCNA), perturbations of many lipid species were strongly correlated with TSH and T3/T4 levels. TSH and the stimulated T3/T4 levels and lipid profiles following SNA001 administration were comparable to those after administration of the reference rhTSH (Thyrogen®). The plasma lipidome and changes in lipid levels after rhTSH stimulation were associated with TSH and T3/T4 concentrations. T3/T4 and lipid profiles were delayed after TSH stimulation. Such phenomena require further exploration.
A New Classification of Anterior Choroidal Artery Aneurysms and Its Clinical Application
Authors: Duan Yu , Qin Xuanfeng , An Qinqzhu , Liu Yikui , Li Jian , Chen Gong
Published: March 2021

Background and Purpose: The aim of this study was to compare the different subtypes of anterior choroidal artery (AChoA) aneurysm based on a new classification and to analyze the risk factors according to individual endovascular treatment (EVT).

Methods: In the new classification, AChoA aneurysms are classified into independent type (I type) and dependent type (II type) based on the relationship between the AChoA and the aneurysm. II type aneurysms have three subtypes, IIa (neck), IIb (body), and IIc (direct). We retrospectively analyzed 52 cases of AChoA aneurysm treated in our center between 2015 to 2019. There were 13 (25.0%) I type aneurysms, 24 (46.2%) IIa aneurysms, 15 (28.8%) IIb aneurysms, and no IIc type; 28 cases had a subarachnoid hemorrhage. According to our preoperative EVT plan for the different subtypes: II type should achieve Raymond-Roy Occlusion Class 1 (RROC 1) where possible. To protect the AChoA, it is best to preserve the neck of the IIa type aneurysms (RROC 2), and RROC 3 is enough for IIb type.

Results: Ten asymptomatic cases with minimal aneurysms were treated conservatively. Of the other cases, 42 were treated with individualized EVT (26 with a simple coil, 6 with balloon-assisted coiling, 7 with stent-assisted coiling, and 3 by flow diverter. Different subtypes had different RROC (Z = 14.026, P = 0.001). IIb type aneurysms (χ2 = 7.54, P = 0.023) were one of the factors related to temporary or permanent AChoA injury during surgery. Overall, two patients (IIa = 1, IIb = 1) developed contralateral hemiparesis.

Conclusions: The new classification diagram clearly shows the features of all types of AChoA aneurysm and makes EVT planning more explicit. The II type (particularly IIb) was a potential risk factor for AChoA injury.
Stroke Treatment With PAR-1 Agents to Decrease Hemorrhagic Transformation
Authors: Lyden Patrick D. , Pryor Kent E. , Minigh Jennifer , Davis Thomas P. , Griffin John H. , Levy Howard , Zlokovic Berislav V.
Published: March 2021

Ischemic stroke is the most widespread cause of disability and a leading cause of death in developed countries. To date, the most potent approved treatment for acute stroke is recanalization therapy with thrombolytic drugs such as tissue plasminogen activator (rt-PA or tPA) or endovascular mechanical thrombectomy. Although tPA and thrombectomy are widely available in the United States, it is currently estimated that only 10–20% of stroke patients get tPA treatment, in part due to restrictive selection criteria. Recently, however, tPA and thrombectomy selection criteria have loosened, potentially allowing more patients to qualify. The relatively low rate of treatment may also reflect the perceived risk of brain hemorrhage following treatment with tPA. In translational research and a single patient study, protease activated receptor 1 (PAR-1) targeted therapies given along with thrombolysis and thrombectomy appear to reduce hemorrhagic transformation after recanalization. Such adjuncts may likely enhance the availability of recanalization and encourage more physicians to use the recently expanded selection criteria for applying recanalization therapies. This narrative review discusses stroke therapies, the role of hemorrhagic transformation in producing poor outcomes, and presents the data suggesting that PAR-1 acting agents show promise for decreasing hemorrhagic transformation and improving outcomes.
Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein–Barr Virus-Specific T Cell Therapy
Authors: Ioannides Zara A. , Csurhes Peter A. , Douglas Nanette L. , Mackenroth Gem , Swayne Andrew , Thompson Kate M. , Hopkins Tracey J. , Green Kerryn A. , Blum Stefan , Hooper Kaye D. , Wyssusek Kerstin H. , Coulthard Alan , Pender Michael P.
Published: March 2021

Background: Increasing evidence indicates a role for Epstein–Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the central nervous system because of defective cytotoxic CD8+ T cell immunity. We have previously reported results of a phase I clinical trial of autologous EBV-specific T cell therapy in MS 6 months after treatment.

Objective: To investigate longer-term outcomes in MS patients who received autologous EBV-specific T cell therapy.

Methods: We assessed participants 2 and 3 years after completion of T cell therapy.

Results: We collected data from all 10 treated participants at year 2 and from 9 participants at year 3. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year 2, including reduced fatigue in three participants, and reduced Expanded Disability Status Scale score in two participants. Three participants experienced a sustained improvement in at least some symptoms at year 3. More sustained improvement was associated with higher EBV-specific CD8+ T cell reactivity in the administered T cell product.

Conclusion: Autologous EBV-specific T cell therapy is well-tolerated, and some degree of clinical improvement can be sustained for up to 3 years after treatment.
Assisted Suicide in Parkinsonian Disorders
Authors: Nuebling Georg S. , Butzhammer Elisabeth , Lorenzl Stefan
Published: March 2021

Background: Due to the high prevalence of suicidal ideation in Parkinson's Disease (PD) and exploratory data indicating a similar prevalence in atypical Parkinsonian disorders (APD), we sought to determine the frequency of assisted suicide (AS) as well as factors driving these decisions in PD and APD.

Methods: Retrospective chart analysis (2006-2012) at a Swiss Right-to-Die organization. Patients with PD and APD who completed AS were analyzed concerning disease state, symptom burden, medication, and social factors.

Results: We identified 72 patients (PD = 34, PSP = 17, MSA = 17, CBS = 4; 7.2% of all AS cases), originating mainly from Germany (41.7%), Great Britain (29.2%), and the US (8.3%). Predominant symptoms at the time of application were immobility (PD/APD: 91%/97%), helplessness (63%/70%), pain (69%/19%), dysarthria (25%/32%), and dysphagia (19%/59%). APD patients generally showed a higher symptom burden and a higher frequency of diagnosed depression (8.8%/28.9%). While most patients with diagnosed depression received antidepressants (80%), other symptoms such as pain (59%) were treated less consistently. Of note, time from diagnosis to application differed greatly between PD (8.5 ± 6.8 years) and APD (1.5 ± 1.3 years, p < 0.0001).

Conclusions: In our analysis, Parkinsonian disorders appeared to be overrepresented as a cause of AS considering the prevalence of these diseases. The observation that assisted suicide is sought early after initial diagnosis in APD implies the need for early comprehensive psychological support of these patients and their relatives.
Brain Development From Newborn to Adolescence: Evaluation by Neurite Orientation Dispersion and Density Imaging
Authors: Zhao Xueying , Shi Jingjing , Dai Fei , Wei Lei , Zhang Boyu , Yu Xuchen , Wang Chengyan , Zhu Wenzhen , Wang He
Published: March 2021

Neurite orientation dispersion and density imaging (NODDI) is a diffusion model specifically designed for brain magnetic resonance imaging. Despite recent studies suggesting that NODDI modeling might be more sensitive to brain development than diffusion tensor imaging (DTI), these studies were limited to a relatively small age range and mainly based on the manually operated region of interest analysis. Therefore, this study applied NODDI to investigate brain development in a large sample size of 214 subjects ranging in ages from 0 to 14. The whole brain was automatically segmented into 122 regions. The maturation trajectory of each region was characterized by the time course of diffusion metrics and further quantified using nonlinear regression. The NODDI-derived metrics, neurite density index (NDI) and orientation dispersion index (ODI), increased with age. And these two metrics were superior to the DTI-derived metrics in SVM regression models of age. The NDI in white matter exhibited a more rapid growth than that in gray matter (including the cortex and deep nucleus). These diffusion indicators experienced conspicuous increases during early childhood and the growth speed slowed down in adolescence. Region-specific maturation patterns were described throughout the brain, including white matter, cortical and deep gray matter. These development patterns were evaluated and discussed on the basis of NODDI’s model assumptions. To summarize, this study verified the high sensitivity of NODDI to age over a crucial developmental period from newborn to adolescence. Moreover, the existing knowledge of brain development has been complemented, suggesting that NODDI has a potential capability in the investigation of brain development.
Neural Correlates of Auditory Pattern Learning in the Auditory Cortex
Authors: Kang Hijee , Auksztulewicz Ryszard , An Hyunjung , Abi Chacra Nicolas , Sutter Mitchell L. , Schnupp Jan W. H.
Published: March 2021

Learning of new auditory stimuli often requires repetitive exposure to the stimulus. Fast and implicit learning of sounds presented at random times enables efficient auditory perception. However, it is unclear how such sensory encoding is processed on a neural level. We investigated neural responses that are developed from a passive, repetitive exposure to a specific sound in the auditory cortex of anesthetized rats, using electrocorticography. We presented a series of random sequences that are generated afresh each time, except for a specific reference sequence that remains constant and re-appears at random times across trials. We compared induced activity amplitudes between reference and fresh sequences. Neural responses from both primary and non-primary auditory cortical regions showed significantly decreased induced activity amplitudes for reference sequences compared to fresh sequences, especially in the beta band. This is the first study showing that neural correlates of auditory pattern learning can be evoked even in anesthetized, passive listening animal models.
The Insula Is a Hub for Functional Brain Network in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis
Authors: Li Chunyan , Pang Xiaomin , Shi Ke , Long Qijia , Liu Jinping , Zheng Jinou
Published: March 2021

Background

In recent years, imaging technologies have been rapidly evolving, with an emphasis on the characterization of brain structure changes and functional imaging in patients with autoimmune encephalitis. However, the neural basis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and its linked cognitive decline is unclear. Our research aimed to assess changes in the functional brain network in patients with anti-NMDAR encephalitis and whether these changes lead to cognitive impairment.

Methods

Twenty-one anti-NMDAR encephalitis patients and 22 age-, gender-, and education status-matched healthy controls were assessed using resting functional magnetic resonance imaging (fMRI) scanning and neuropsychological tests, including the Hamilton Depression Scale (HAMD24), the Montreal Cognitive Assessment (MoCA), and the Hamilton Anxiety Scale (HAMA). A functional brain network was constructed using fMRI, and the topology of the network parameters was analyzed using graph theory. Next, we extracted the aberrant topological parameters of the functional network as seeds and compared causal connectivity with the whole brain. Lastly, we explored the correlation of aberrant topological structures with deficits in cognitive performance.

Results

Relative to healthy controls, anti-NMDAR encephalitis patients exhibited decreased MoCA scores and increased HAMA and HAMD24scores (p< 0.05). The nodal clustering coefficient and nodal local efficiency of the left insula (Insula_L) were significantly decreased in anti-NMDAR encephalitis patients (p< 0.05 following Bonferroni correction). Moreover, anti-NMDAR encephalitis patients showed a weakened causal connectivity from the left insula to the left inferior parietal lobe (Parietal_Inf_L) compared to healthy controls. Conversely, the left superior parietal lobe (Parietal_sup_L) exhibited an enhanced causal connectivity to the left insula in anti-NMDAR encephalitis patients compared to controls. Unexpectedly, these alterations were not correlated with any neuropsychological test scores.

Conclusion

This research describes topological abnormalities in the functional brain network in anti-NMDAR encephalitis. These results will be conducive to understand the structure and function of the brain network of patients with anti-NMDAR encephalitis and further explore the neuropathophysiological mechanisms.
Primary Tumor Resection for Rectal Cancer With Unresectable Liver Metastases: A Chance to Cut Is a Chance for Improved Survival
Authors: Chen Jia-nan , Shoucair Sami , Wang Zheng , Habib Joseph R. , Zhao Fu-qiang , Yu Jun , Liu Zheng , Liu Qian
Published: March 2021

Background: About half of the patients with rectal cancer will develop liver metastasis during the course of their illness. Unfortunately, a large proportion of these metastases are unresectable. Surgical resection of the primary tumor vs. palliative treatment in patients with unresectable synchronous liver metastases remains controversial.

Methods: Patients with rectal cancer with surgically unresectable liver metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2015. According to different treatment modalities, patients were divided into a primary tumor resection group and a non-resection group. Rates of primary tumor resection and survival were calculated for each year. Kaplan–Meier methods and Cox regression models were used to assess long-term survival. Multivariable logistic regression models were used to evaluate factors potentially associated with primary tumor resection.

Results: Among 1,957 patients, 494 (25.2%) had undergone primary tumor resection. Patients with primary tumor resection had significantly better 5-year survival rate (27.2 vs. 5.6%, P < 0.001) compared to the non-resection group. Chemoradiotherapy with primary site resection was associated with the longest mean and 5-year OS (44.7 months, 32.4%). The Cox regression analyses of the subgroup indicated that patients who underwent primary tumor resection had improved survival compared with those who did not undergo resection in all 25 subgroups. Factors associated with primary tumor resection were well or moderately differentiated tumor grade, undergoing radiation, and primary tumor size <5 cm.

Conclusions: The majority of patients with rectal cancer with unresectable liver metastases did not undergo primary tumor resection. Our results indicate that resection of the primary tumor appears to offer the greatest chance of survival. Prospective studies are needed to confirm these results.
Protective Factors for Early Childhood Caries in 3-Year-Old Children in Poland
Authors: Olczak-Kowalczyk Dorota , Gozdowski Dariusz , Turska-Szybka Anna
Published: March 2021

Background: Early childhood caries (ECC) remains highly prevalent in preschool children worldwide. Dental caries affects every second 3-year-olds in Poland. The aim of the study was to assess protective factors for ECC in 3-year-olds.

Methods: A cross-sectional survey was conducted in 2017 among 3-year-olds attending kindergartens in all 16 provinces of Poland. The questionnaire included socioeconomic factors, and oral health behaviors. Decayed, missing due to caries and filled teeth and surfaces were assessed. Caries indices (dmft and dmfs), percentage of caries-free and severe ECC (S-ECC) were calculated. The Student's t-test, Spearman correlation, univariate and multivariate logistic regression (the odds ratios (OR) and adjusted odds ratios (AOR): confounding factors: socioeconomic conditions, oral health behaviors) were performed; p < 0.05.

Results: A total of 1,638 children were included. ECC was confirmed in 41.1%; S-ECC in 23.4%. The dmft index was 1.85 ± 3.14, dmfs = 2.99 ± 6.56. Spearman correlation [socioeconomic factors, especially mother's education (r = −0.148, p < 0.001) and family's economic status (r = −0.071, p = 0.004)], despite were statistically significant, indicate very weak relationships with dmft index. After 12th month of life not giving any beverages before bedtime and at night, but water or unsweetened milk only, healthy snacking (sandwiches, fresh fruit), or water on a daily basis decreases the probability of caries development (for S-ECC: OR = 0.37, AOR = 0.47, AOR2 = 0.37; p < 0.01), even if inappropriate dietary behaviors or hygiene practices were simultaneously present. Brushing of a child's teeth twice a day lowered the odds of caries (for S-ECC: OR = 0.78, p = 0.031; AOR = 0.81, p = 0.081; AOR2 = 0.84, p = 0.131), but this effect was less intense when inappropriate dietary behaviors were accounted for. Children of parents with good self-assessment of their teeth were more often caries-free (61.4 vs. 42.9%; p = 0.006) and had lower dmft indices (1.67 vs. 2.93; p = 0.002).

Conclusions: Preventing a child after 12th month of life from getting any beverages before bedtime, water or unsweetened milk only, sandwiches and fresh fruit as snacks, or water given to on a daily basis, tooth brushing twice a day decrease the odds of caries in 3-year-olds. Diet appears to have primary significance in the etiology of ECC, since tooth brushing can only partly attenuate the impact of inappropriate dietary behaviors on dental caries. Children are more often caries-free and have lower severity of caries if their parents' dentition is self-assessed as healthy.
Efficacy and Safety of TangWang Prescription for Type 2 Non-Proliferative Diabetic Retinopathy: A Study Protocol for a Randomized Controlled Trial
Authors: Jin De , Zhang Yuehong , Zhang Yuqing , Huang Wenjing , Meng Xiang , Yang Fan , Bao Qi , Zhang Meizhen , Yang Yanan , Ni Qing , Lian Fengmei , Tong Xiaolin
Published: March 2021

Background: Diabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes mellitus (DM), which results in blindness among adults worldwide. Presently, the efficacy of drug treatments for diabetic retinopathy (DR) is not satisfactory, thus urgently necessitating effective drug treatment measures. TangWang prescription (TWP) has been found to have retinal protection effects in previous clinical and basic research. However, there is a lack of rigorous, randomized, and controlled studies. This study aims to evaluate the efficacy and safety of TWP in delaying the development of DR.

Methods: This study is a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial, consisting of 384 participants to be randomized in a 1:1 ratio in the treatment and control groups. Furthermore, the treatment and control groups will be administered the TangWang prescription and the placebo, respectively, each at a dose of one bag twice a day. The study period will last for 48 weeks. The primary outcome measure will be the changes in the degree of retinal microvascular lesions before and after treatment. The secondary outcome will be changes in the degree of hemangioma, microvascular bleeding, microvascular leakage, macular edema, and vision. All statistical tests will be two-sided, and a p < 0.05 will be considered statistically significant.

Discussion: We hypothesize that the patients with DR will benefit from TangWang prescription, and in addition to the central random system and platform of dynamic information collection, the patients’ conditions will be monitored, and the data collected for analysis. If successful, this study will provide evidence that the TWP formulation delays in the progression of DR.

Trial registration: The design of this trial has been registered with the ClinicalTrials.gov (NCT03025399).
Activation of PI3K/AKT/mTOR Pathway Causes Drug Resistance in Breast Cancer
Authors: Dong Chao , Wu Jiao , Chen Yin , Nie Jianyun , Chen Ceshi
Published: March 2021

Although chemotherapy, targeted therapy and endocrine therapy decrease rate of disease recurrence in most breast cancer patients, many patients exhibit acquired resistance. Hyperactivation of the PI3K/AKT/mTOR pathway is associated with drug resistance and cancer progression. Currently, a number of drugs targeting PI3K/AKT/mTOR are being investigated in clinical trials by combining them with standard therapies to overcome acquired resistance in breast cancer. In this review, we summarize the critical role of the PI3K/AKT/mTOR pathway in drug resistance, the development of PI3K/AKT/mTOR inhibitors, and strategies to overcome acquired resistance to standard therapies in breast cancer.
Population Pharmacokinetic Study of Cefathiamidine in Infants With Augmented Renal Clearance
Authors: Du Bin , Zhou Yue , Tang Bo-Hao , Wu Yue-E , Yang Xin-Mei , Shi Hai-Yan , Yao Bu-Fan , Hao Guo-Xiang , You Dian-Ping , van den Anker John , Zheng Yi , Zhao Wei
Published: March 2021

Objectives: Augmented renal clearance (ARC) of primarily renally eliminated antibacterial agents may result in subtherapeutic antibiotic concentrations and, as a consequence, worse clinical outcomes. Cefathiamidine is frequently used as empirical antimicrobial therapy in children with ARC, but pharmacokinetic studies in infants are lacking. This population pharmacokinetic study in infants with ARC was conducted to determine optimal dosing regimens of cefathiamidine.

Methods: The population pharmacokinetics was conducted in 20 infants treated with cefathiamidine. Plasma samples of cefathiamidine were collected using opportunistic sampling, and the concentrations were detected by UPLC-MS/MS. Data analysis was performed to determine pharmacokinetic parameters and to characterize pharmacokinetic variability of cefathiamidine using nonlinear mixed effects modelling (NONMEM) software program.

Results: The data (n = 36) from 20 infants (age range, 0.35–1.86 years) with ARC were fitted best with a 1-compartment model. Allometrically scaled weight and age as significant covariates influenced cefathiamidine pharmacokinetics. The median (range) values of estimated clearance and the volume of distribution were 0.22 (0.09–0.29) L/h/kg and 0.34 (0.24–0.41) L/kg, respectively. Monte Carlo simulations showed that the cefathiamidine doses of 100 mg/kg/day q12 h, 50 mg/kg/day q8 h and 75 mg/kg/day q6 h were chosen for bacteria with MIC 0.25, 0.5 and 2 mg/L, respectively.

Conclusion: The population pharmacokinetic model of cefathiamidine for infants with ARC was developed. The PTA - based dosing regimens were recommended based on the final model.
Research and Development of a Transportable Optical Ground Station in NICT: The Results of the First Performance Test
Authors: Saito Yoshihiko , Takenaka Hideki , Shiratama Koichi , Munemasa Yasushi , Carrasco-Casado Alberto , Trinh Phuc V. , Suzuki Kenji , Fuse Tetsuharu , Takahashi Yasuhiro , Kubo-oka Toshihiro , Toyoshima Morio
Published: March 2021

In recent years, the necessity of free-space optical (FSO) communications has increased as a method for realizing high-speed communications between satellites and the ground. However, one disadvantage of FSO communications is the significant influence of the atmosphere. Specifically, FSO communications cannot be utilized under certain atmospheric conditions, especially in the presence of clouds. One of the solutions to this problem is the site diversity technique, which makes it possible to select a given ground station with better atmospheric conditions among a number of fixed ground stations. The other solution is to prepare a ground station that can be moved to a place with better atmospheric conditions. We applied the latter method and developed a transportable optical ground station in NICT. We utilize a realistic telescope diameter, which is about 30 cm at the maximum, capable of being set up quickly, and with a pointing accuracy of about 100 µrad. In addition, it is necessary to prepare a fine-pointing optical system that performs tracking with about 1/10 of the pointing accuracy of the telescope. In this paper, we report the results of the first performance test of the transportable optical ground station in NICT.
Transgenerational Plasticity in Flower Color Induced by Caterpillars
Authors: Sobral Mar , Neylan Isabelle P. , Narbona Eduardo , Dirzo Rodolfo
Published: March 2021

Variation in flower color due to transgenerational plasticity could stem directly from abiotic or biotic environmental conditions. Finding a link between biotic ecological interactions across generations and plasticity in flower color would indicate that transgenerational effects of ecological interactions, such as herbivory, might be involved in flower color evolution. We conducted controlled experiments across four generations of wild radish (Raphanus sativus, Brassicaceae) plants to explore whether flower color is influenced by herbivory, and to determine whether flower color is associated with transgenerational chromatin modifications. We found transgenerational effects of herbivory on flower color, partly related to chromatin modifications. Given the presence of herbivory in plant populations worldwide, our results are of broad significance and contribute to our understanding of flower color evolution.
The Influence of the Inconsistent Color Presentation of the Original Price and Sale Price on Purchase Likelihood
Authors: Liang Shichang , Dong Xuebing , Yan Yanling , Chang Yaping
Published: March 2021

Retailers like to use different colors to present the sale price and original price when they are presenting a promotion price. How does the inconsistent color presentation of the prices influence consumers’ purchase likelihood? The extant research does not consider this question. This article will address this question. Drawing on incongruence theory and the persuasion knowledge model (PKM), this article proposes that when the color of the sale price is inconsistent (vs. consistent) with that of the original price, consumers show less preference for the sale price. The reason is that consumers perceive the price as being less trustworthy, which leads to a lower purchase likelihood. Furthermore, this effect is affected by the brand awareness of products. Specifically, when products are less-known brands, the inconsistent (vs. consistent) colors of the sale price and original price will lead to a lower purchase likelihood. In contrast, when products are well-known brands, the inconsistent (vs. consistent) colors of the sale price and original price will lead to a high purchase likelihood. In this article, four studies are used to verify these hypotheses, and implications of theory and practice of the present research are discussed.
Let Me Make You Happy, and I'll Tell You How You Look Around: Using an Approach-Avoidance Task as an Embodied Emotion Prime in a Free-Viewing Task
Authors: Czeszumski Artur , Albers Friederike , Walter Sven , König Peter
Published: March 2021

The embodied approach of human cognition suggests that concepts are deeply dependent upon and constrained by an agent's physical body's characteristics, such as performed body movements. In this study, we attempted to broaden previous research on emotional priming, investigating the interaction of emotions and visual exploration. We used the joystick-based approach-avoidance task to influence the emotional states of participants, and subsequently, we presented pictures of news web pages on a computer screen and measured participant's eye movements. As a result, the number of fixations on images increased, the total dwell time increased, and the average saccade length from outside of the images toward the images decreased after the bodily congruent priming phase. The combination of these effects suggests increased attention to web pages' image content after the participants performed bodily congruent actions in the priming phase. Thus, congruent bodily interaction with images in the priming phase fosters visual interaction in the subsequent exploration phase.
The Self-Regulation of Learning – Self-Report Scale for Sport Practice: Validation of an Italian Version for Football
Authors: Reverberi Eleonora , Gozzoli Caterina , D’Angelo Chiara , Lanz Margherita , Sorgente Angela
Published: March 2021

Self-regulation of learning (SRL) is a key psychological factor that supports young athletes aiming to reach the elite level by promoting their involvement in deliberate practice. We contributed to the validation of the Italian version of the Bartulovic et al. (2017) Self-Regulation of Learning – Self-Report Scale for Sport Practice by testing its factorial structure, reliability, and measurement invariance among elite and non-elite football players, involving 415 male professional, semi-professional, and amateur youth academy players (Mage = 16.2, SD = 1.51). The original six-factor structure (planning, reflection, effort, self-efficacy, self-monitoring, and evaluation) did not fit the data well and a five-factor solution (where self-monitoring and evaluation items load on the same factor, named “self-supervision”) was a better fit. This five-factor solution was measurement invariant across groups of elite and non-elite athletes. We found that elite athletes scored significantly higher than non-elite ones in each SRL subprocess. Implications for future validation studies and for the use of this tool are discussed.
The Impact of Sexualized Video Game Content and Cognitive Load on State Rape Myth Acceptance
Authors: Noël Tania , Larøi Frank , Burnay Jonathan
Published: March 2021

The potential negative impact of sexualized video games on attitudes toward women is an important issue. Studies that have examined this issue are rare and contain a number of limitations. Therefore, it largely remains unclear whether sexualized video games can have an impact on attitudes toward women. This study examined the consequences of sexualized video game content and cognitive load (moderator) on rape victim blame and rape perpetrator blame (used as a proxy of rape myth acceptance), and whether the degree of humanness of the victim and of the perpetrator mediated these effects. Participants (N = 142) played a video game using sexualized or non-sexualized female characters. Cognitive load was manipulated by setting the difficulty level of the game to low or high. After gameplay, participants read a rape date story, and were then asked to judge the victim’s and the perpetrator’s degree of responsibility and humanness. Based on the General Aggression Model (GAM), it was hypothesized that playing the video game with a sexualized content would increase the responsibility assigned to the victim and diminish the responsibility assigned to the perpetrator. Further, degree of humanness of the victim and the perpetrator was expected to mediate this relation. The results were partially consistent with these predictions: Playing a video game containing sexualized female characters increased rape victim blame when cognitive load was high, but did not predict degree of humanness accorded to the victim. Concerning the perpetrator, video game sexualization did not influence responsibility, but partly influenced humanness. This study concludes that video games impact on attitudes toward women and this, in part, due to its interactive nature.
Suppression of Psychological Needs Among Beginning Teachers: A Self-Determination Theory Perspective on the Induction Process in Bedouin Schools
Authors: Kaplan Haya
Published: March 2021

The study focuses on the emotional-motivational experiences of Bedouin-Arab beginning teachers during the induction period, from the perspective of Self-Determination Theory. A phenomenological study was employed. Seventy-four teachers participated, 62 of whom completed open questionnaires, while semi-structured interviews were conducted with 12 other participants. The findings indicate that the beginning teachers reported experiences of coercion, exploitation, and gender-based discrimination (autonomy suppression). They also experienced a judgmental attitude, lack of assistance, and difficulties with students (competence suppression), and their sense of relatedness to the school is impaired due to cultural factors (relatedness suppression). As a result, they expressed controlled motivation, a sense of burnout, stress, impaired well-being and disengagement in school. They also suppressed their students' autonomy. At the same time, the findings also show that when the teachers experience a sense of need satisfaction, they integrate well into the school. These findings indicate the necessity for establishing a need-supportive school environment for beginning teachers during their induction period.