bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study of high-intensity interval training in older adults with treatment naïve chronic lymphocytic leukemia
Authors: MacDonald Grace , Sitlinger Andrea , Deal Michael A. , Hanson Erik D. , Ferraro Stephanie , Pieper Carl F. , Weinberg J. Brice , Brander Danielle M. , Bartlett David B. 
Published: November 2021

AbstractChronic lymphocytic leukemia (CLL) is the most common leukemia in the USA, affecting predominantly older adults. CLL is characterized by low physical fitness, reduced immunity, and increased risk of secondary malignancies and infections. One approach to improving CLL patients’ physical fitness and immune functions may be participation in a structured exercise program. The aims of this pilot study were to examine physical and immunological changes, and feasibility of a 12-week high-intensity interval training (HIIT) combined with muscle endurance-based resistance training on older adults with treatment naïve CLL. We enrolled eighteen participants with CLL aged 64.9 ± 9.1 years and assigned them to groups depending on distance lived from our fitness center. Ten participants (4 M/6F) completed HIIT and six participants (4 M/2F) completed a non-exercising control group (Controls). HIIT consisted of three 30-min treadmill sessions/week plus two concurrent 30-min strength training sessions/week. Physical and immunological outcomes included aerobic capacity, muscle strength and endurance, and natural killer (NK) cell recognition and killing of tumor cells. We confirmed feasibility if > 70% of HIIT participants completed > 75% of prescribed sessions and prescribed minutes, and if > 80% of high-intensity intervals were at a heart rate corresponding to at least 80% of peak aerobic capacity (VO2peak). Results are presented as Hedge’s G effect sizes (g), with 0.2, 0.5 and 0.8 representing small, medium and large effects, respectively. Following HIIT, leg strength (g = 2.52), chest strength (g = 1.15) and seated row strength (g = 3.07) were 35.4%, 56.1% and 39.5% higher than Controls, respectively, while aerobic capacity was 3.8% lower (g = 0.49) than Controls. Similarly, following HIIT, in vitro NK-cell cytolytic activity against the K562 cell line (g = 1.43), OSU-CLL cell line (g = 0.95), and autologous B-cells (g = 1.30) were 20.3%, 3.0% and 14.6% higher than Controls, respectively. Feasibility was achieved, with HIIT completing 5.0 ± 0.2 sessions/week and 99 ± 3.6% of the prescribed minutes/week at heart rates corresponding to 89 ± 2.8% of VO2peak. We demonstrate that 12-weeks of supervised HIIT combined with muscle endurance-based resistance training is feasible, and that high adherence and compliance are associated with large effects on muscle strength and immune function in older adults with treatment naïve CLL.Trial registration: NCT04950452.
Drug repurposing for COVID-19 using graph neural network and harmonizing multiple evidence
Authors: Hsieh Kanglin , Wang Yinyin , Chen Luyao , Zhao Zhongming , Savitz Sean , Jiang Xiaoqian , Tang Jing , Kim Yejin 
Published: November 2021

AbstractSince the 2019 novel coronavirus disease (COVID-19) outbreak in 2019 and the pandemic continues for more than one year, a vast amount of drug research has been conducted and few of them got FDA approval. Our objective is to prioritize repurposable drugs using a pipeline that systematically integrates the interaction between COVID-19 and drugs, deep graph neural networks, and in vitro/population-based validations. We first collected all available drugs (n = 3635) related to COVID-19 patient treatment through CTDbase. We built a COVID-19 knowledge graph based on the interactions among virus baits, host genes, pathways, drugs, and phenotypes. A deep graph neural network approach was used to derive the candidate drug’s representation based on the biological interactions. We prioritized the candidate drugs using clinical trial history, and then validated them with their genetic profiles, in vitro experimental efficacy, and population-based treatment effect. We highlight the top 22 drugs including Azithromycin, Atorvastatin, Aspirin, Acetaminophen, and Albuterol. We further pinpointed drug combinations that may synergistically target COVID-19. In summary, we demonstrated that the integration of extensive interactions, deep neural networks, and multiple evidence can facilitate the rapid identification of candidate drugs for COVID-19 treatment.
Survival outcomes of management in metastatic gastric adenocarcinoma patients
Authors: Hu Huang-Ming , Tsai Hui-Jen , Ku Hsiu-Ying , Lo Su-Shun , Shan Yan-Shen , Chang Hung-Chi , Chao Yee , Chen Jen-Shi , Chen Shu-Chen , Chiang Chun-Ju , Li Anna Fen-Yau , Wang Hsiu-Po , Wang Tsang-En , Bai Li-Yuan , Wu Ming-Shiang , Chen Li-Tzong , Liu Tsang-Wu , Yang Yi-Hsin 
Published: November 2021

AbstractChemotherapy is generally considered as the main treatment for metastatic gastric adenocarcinoma. The role of gastrectomy for metastatic gastric cancer without obvious symptoms is controversial. The objective of this study is to investigate survival outcomes of treatment modalities using a real-world data setting. A retrospective cohort study was designed using the Taiwan Cancer Registry database. We identified the treatment modalities and used Kaplan–Meier estimates and Cox regressions to compare patient survival outcomes. From 2008 to 2015, 5599 gastric adenocarcinoma patients were diagnosed with metastatic disease (M1). The median overall survival (OS) of patients with surgery plus chemotherapy had the longest survival of 14.2 months. The median OS of the patients who received chemotherapy alone or surgery alone was 7.0 and 3.9, respectively. Age at diagnosis, year of diagnosis, tumor grade, and treatment modalities are prognostic factors for survival. The hazard ratios for patients who received surgery plus chemotherapy, surgery alone, and supportive care were 0.47 (95% CI 0.44–0.51), 1.22 (95% CI 1.1–1.36), and 3.23 (95% CI 3.01–3.46), respectively, by multivariable Cox regression analysis when using chemotherapy alone as a referent. Chemotherapy plus surgery may have a survival benefit for some selected gastric adenocarcinoma patients with metastatic disease.
Unexpected benzene oxidation in collisions with superoxide anions
Authors: Guerra Carlos , Kumar Sarvesh , Aguilar-Galindo Fernando , Díaz-Tendero Sergio , Lozano Ana I. , Mendes Mónica , Limão-Vieira Paulo , García Gustavo 
Published: November 2021

AbstractSuperoxide anions colliding with benzene molecules at impact energies from 200 to 900 eV are reported for the first time to form massive complexes. With the aid of quantum chemistry calculations, we propose a mechanism in which a sudden double ionization of benzene and the subsequent electrostatic attraction between the dication and the anion form a stable covalently bonded C6H6O2+ molecule, that evolves towards the formation of benzene-diol conformers. These findings lend support to a model presenting a new high energy anion-driven chemistry as an alternative way to form complex molecules.
Inhibitory properties of crude microalgal extracts on the in vitro replication of cyprinid herpesvirus 3
Authors: Fritzsche Stefanie , Blenk Patrik , Christian Jürgen , Castiglione Kathrin , Becker Anna Maria 
Published: November 2021

AbstractMicroalgae are possible sources of antiviral substances, e.g. against cyprinid herpesvirus 3 (CyHV-3). Although this virus leads to high mortalities in aquacultures, there is no treatment available yet. Hence, ethanolic extracts produced with accelerated solvent extraction from six microalgal species (Arthrospira platensis,Chlamydomonas reinhardtii,Chlorella kessleri,Haematococcus pluvialis,Nostoc punctiformeandScenedesmus obliquus) were examined in this study. An inhibition of the in vitro replication of CyHV-3 could be confirmed for all six species, with the greatest effect for theC. reinhardtiiandH. pluvialiscrude extracts. At still non-cytotoxic concentrations, viral DNA replication was reduced by over 3 orders of magnitude each compared to the untreated replication controls, while the virus titers were even below the limit of detection (reduction of 4 orders of magnitude). When pre-incubating both cells and virus withC. reinhardtiiandH. pluvialisextracts before inoculation, the reduction of viral DNA was even stronger (> 4 orders of magnitude) and no infectious viral particles were detected. Thus, the results of this study indicate that microalgae and cyanobacteria are a promising source of natural bioactive substances against CyHV-3. However, further studies regarding the isolation and identification of the active components of the extracts are needed.
Genetic diversity of Norway spruce ecotypes assessed by GBS-derived SNPs
Authors: Korecký Jiří , Čepl Jaroslav , Stejskal Jan , Faltinová Zuzana , Dvořák Jakub , Lstibůrek Milan , El-Kassaby Yousry A. 
Published: November 2021

AbstractWe investigated the genetic structure of three phenotypically distinct ecotypic groups of Norway spruce (Picea abies) belonging to three elevational classes; namely, low- (acuminata), medium- (europaea),and high-elevation (obovata) form, each represented by 150 trees. After rigorous filtering, we used 1916 Genotyping-by-Sequencing generated SNPs for analysis. Outputs from three multivariate analysis methods (Bayesian clustering algorithm implemented in STRUCTURE, Principal Component Analysis, and the Discriminant Analysis of Principal Components) indicated the presence of a distinct genetic cluster representing the high-elevation ecotypic group. Our findings bring a vital message to forestry practice affirming that artificial transfer of forest reproductive material, especially for stands under harsh climate conditions, should be considered with caution.
Dynamic monitoring of urban built-up object expansion trajectories in Karachi, Pakistan with time series images and the LandTrendr algorithm
Authors: Yan Xinrong , Wang Juanle 
Published: November 2021

AbstractIn the complex process of urbanization, retrieving its dynamic expansion trajectories with an efficient method is challenging, especially for urban regions that are not clearly distinguished from the surroundings in arid regions. In this study, we propose a framework for extracting spatiotemporal change information on urban disturbances. First, the urban built-up object areas in 2000 and 2020 were obtained using object-oriented segmentation method. Second, we applied LandTrendr (LT) algorithm and multiple bands/indices to extract annual spatiotemporal information. This process was implemented effectively with the support of the cloud computing platform of Earth Observation big data. The overall accuracy of time information extraction, the kappa coefficient, and average detection error were 83.76%, 0.79, and 0.57 a, respectively. These results show that Karachi expanded continuously during 2000–2020, with an average annual growth rate of 4.7%. However, this expansion was not spatiotemporally balanced. The coastal area developed quickly within a shorter duration, whereas the main newly added urban regions locate in the northern and eastern inland areas. This study demonstrated an effective framework for extract the dynamic spatiotemporal change information of urban built-up objects and substantially eliminate the salt-and-pepper effect based on pixel detection. Methods used in our study are of general promotion significance in the monitoring of other disturbances caused by natural or human activities.
Self-controlling photonic-on-chip networks with deep reinforcement learning
Authors: Do Nguyen , Truong Dung , Nguyen Duy , Hoai Minh , Pham Cuong 
Published: November 2021

AbstractWe present a novel photonic chip design for high bandwidth four-degree optical switches that support high-dimensional switching mechanisms with low insertion loss and low crosstalk in a low power consumption level and a short switching time. Such four-degree photonic chips can be used to build an integrated full-grid Photonic-on-Chip Network (PCN). With four distinct input/output directions, the proposed photonic chips are superior compared to the current bidirectional photonic switches, where a conventionally sizable PCN can only be constructed as a linear chain of bidirectional chips. Our four-directional photonic chips are more flexible and scalable for the design of modern optical switches, enabling the construction of multi-dimensional photonic chip networks that are widely applied for intra-chip communication networks and photonic data centers. More noticeably, our photonic networks can be self-controlling with our proposed Multi-Sample Discovery model, a deep reinforcement learning model based on Proximal Policy Optimization. On a PCN, we can optimize many criteria such as transmission loss, power consumption, and routing time, while preserving performance and scaling up the network with dynamic changes. Experiments on simulated data demonstrate the effectiveness and scalability of the proposed architectural design and optimization algorithm. Perceivable insights make the constructed architecture become the self-controlling photonic-on-chip networks.
Biallelic inheritance in a single Pakistani family with intellectual disability implicates new candidate gene RDH14
Authors: Pastore Stephen F. , Muhammad Tahir , Harripaul Ricardo , Lau Rebecca , Khan Muhammad Tariq Masood , Khan Muhammad Ismail , Islam Omar , Kang Changsoo , Ayub Muhammad , Jelani Musharraf , Vincent John B. 
Published: November 2021

AbstractIn a multi-branch family from Pakistan, individuals presenting with palmoplantar keratoderma segregate in autosomal dominant fashion, and individuals with intellectual disability (ID) segregate in apparent autosomal recessive fashion. Initial attempts to identify the ID locus using homozygosity-by-descent (HBD) mapping were unsuccessful. However, following an assumption of locus heterogeneity, a reiterative HBD approach in concert with whole exome sequencing (WES) was employed. We identified a known disease-linked mutation in the polymicrogyria gene, ADGRG1, in two affected members. In the remaining two (living) affected members, HBD mapping cross-referenced with WES data identified a single biallelic frameshifting variant in the gene encoding retinol dehydrogenase 14 (RDH14). Transcription data indicate that RDH14 is expressed in brain, but not in retina. Magnetic resonance imaging for the individuals with this RDH14 mutation show no signs of polymicrogyria, however cerebellar atrophy was a notable feature. RDH14 in HEK293 cells localized mainly in the nucleoplasm. Co-immunoprecipitation studies confirmed binding to the proton-activated chloride channel 1 (PACC1/TMEM206), which is greatly diminished by the mutation. Our studies suggest RDH14 as a candidate for autosomal recessive ID and cerebellar atrophy, implicating either disrupted retinoic acid signaling, or, through PACC1, disrupted chloride ion homeostasis in the brain as a putative disease mechanism.
Hydrochemical analysis and identification of open-pit mine water sources: a case study from the Dagushan iron mine in Northeast China
Authors: Liu Qianling , Zhang Zhongjian , Zhang Bin , Mu Wenping , Zhang Huijie , Li Yutao , Xu Nengxiong 
Published: November 2021

AbstractThe identification of open-pit mine water sources is of great significance in preventing water disasters. Combined with hydrochemistry and multivariate statistical analysis, this paper systematically analyzed the hydraulic connections between aquifers and the complex seepage water sources in the pit and roadway of Dagushan iron mine through qualitative analysis and quantitative calculation. According to the hydrochemical characteristics of the study area, the causes of seepage water at different positions in the mining area were reasonably explained. The results show that there is a possible hydraulic connection or similar source of water body between the bedrock fissure aquifer and the eluvium pore aquifer. The water seepage of 2# roadway mainly comes from bedrock fissure aquifer in the north of mining area. The reason for serious water seepage in the 3# roadway and the western side of the pit is that the fault connects the shallow alluvial pore aquifer and bedrock fissure aquifer. The source of water on the southern side pit comes from the river and groundwater on the southern side of the mine. The results presented here provide significant guidance for the management of mine water seepage problems.
Synthesis and characterization of genistein magnetic molecularly imprinted polymers and their application in soy sauce products
Authors: Xie Ziqi , Luo Yunjing , Na Zhen , Zhang Wei , Zong Yufei 
Published: November 2021

AbstractIn this study, a novel method based on genistein magnetic molecularly imprinted polymers (Gen-MMIPs) was developed utilizing a surface molecular imprinting technique, in which genistein was used as the template molecule and Fe3O4 was used as the carrier. The synthesis of Gen-MMIPs was characterized by using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), which indicated that the diameter of the Gen-MMIPs was approximately 500 nm. Via analysis with a vibrating sample magnetometer (VSM), the saturation magnetization of Gen-MMIPs was determined to be 24.79 emu g−1. Fourier transform infrared (FT-IR) spectroscopy showed that polymer groups were on the surface of the magnetic carrier. Adsorption experiments suggested that the genistein adsorption capability of Gen-MMIPs was 5.81 mg g−1, and adsorption equilibrium was achieved within 20 min. Gen-MMIPs as dispersive solid-phase extraction (dSPE) adsorbents combined with HPLC were used to selectively separate genistein in soy sauce samples, and the recoveries ranged from 85.7 to 88.5% with relative standard deviations (RSDs) less than 5%, which proved that this method can be used for the detection of genistein residues in real samples.
Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia
Authors: Wang S. , Li J. , Song M. , Yan P. , Ju X. , Liu J. , Wang C. , Shi J. 
Published: November 2021

AbstractValproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5–1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 (CYP2C19*2 G681A rs4244285 and CYP2C19*3 G636A rs4986893) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid were significantly higher in patients with CYP2C19 *1/*2 genotype (P < 0.01) or CYP2C19 *2/*3 genotype (P < 0.01) than in those with CYP2C12 *1/*1 genotype. The mean concentration/dose ratios of valproic acid were significantly higher in patients with 1 (P < 0.01) or 2 (P < 0.01) mutated alleles for CYP2C19 than in those without mutated alleles. And the post hoc analysis revealed that the result has acceptable statistical (power (1 – β) = 0.8486 at type I  level of 0.05) to support the observed significant associations for CYP2C19 SNPs and serum C/D ratios of valproic acid. The findings of this study suggest that the genetic polymorphisms of CYP2C19 significantly affect the steady-state serum concentrations of valproic acid in Chinese Han population. The determination of the CYP2C19 genotypes may be useful for dosing adjustment in schizophrenia patients on valproic acid therapy.
Shift in demographic structure and increased reproductive activity of loggerhead turtles in the French Mediterranean Sea revealed by long-term monitoring
Authors: Girard Fanny , Catteau Sidonie , Gambaiani Delphine , Gérigny Olivia , Sénégas Jean Baptiste , Moisson Pierre , Claro Françoise 
Published: November 2021

AbstractClimate-induced environmental changes are profoundly impacting marine ecosystems and altering species distribution worldwide. Migratory organisms, including sea turtles, are expected to be particularly sensitive to these variations. Here, we studied changes in the size structure and reproductive activity of loggerhead turtles in the French Mediterranean over 30 years. Overall, there was a significant increase in the size of observed loggerheads between 1990 and 2020. However, this increase was only significant during the breeding/nesting season (May to September) and was driven by the increased presence of adults. Furthermore, nesting activity along the French coast was detected in 2002 for the first time in more than 50 years, and has become frequent after 2014, with nests discovered every year. The number of eggs laid as well as incubation duration and success varied among sites but fell within the range reported at established Mediterranean nesting sites. These observations, along with recent reports of breeding activity and evidence of significant sea surface warming, suggest that the north-western Mediterranean basin has become increasingly suitable to loggerhead turtles. We postulate that this range expansion is the result of climate change and propose that emerging nesting activity in France should be closely monitored and guarded against human activities.
Oral microbiome associated with lymph node metastasis in oral squamous cell carcinoma
Authors: Eun Young-Gyu , Lee Jung-Woo , Kim Seung Woo , Hyun Dong-Wook , Bae Jin-Woo , Lee Young Chan 
Published: November 2021

AbstractOral microbiota can alter cancer susceptibility and progression by modulating metabolism and inflammation. We assessed the association between the oral microbiome and lymph node (LN) metastasis in oral squamous cell carcinoma (OSCC). We collected a total of 54 saliva samples from patients with OSCC before surgery. LN metastasis was assessed based on postoperative pathological examination. We used QIIME2, linear discriminant analysis effect size (LEfSe), and PICRUSt2 methods to analyze microbial dysbiosis. A random forest classifier was used to assess whether the oral microbiome could predict LN metastasis. Among the 54 OSCC samples, 20 had LN metastasis, and 34 had no evidence of metastasis. There was a significant difference in β-diversity between the metastasis and no metastasis groups. Through LEfSe analysis, the metastasis group was enriched in the genera Prevotella, Stomatobaculum, Bifidobacterium, Peptostreptococcaceae, Shuttleworthia and Finegoldia. Pathways related to signal peptidase II were predominant in the no metastasis group. The RF model showed a modestly high accuracy for predicting metastasis. Differences in microbial community composition and functions were observed in the oral microbiome of patients with OSCC with and without LN metastasis. However, the finding that specific taxa may be associated with LN metastasis should be verified in a further prospective study.