bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene‐Gene Interactions of Gemcitabine Metabolizing‐Enzyme Genes hCNT3 and WEE1 for Preventing Severe Gemcitabine‐Induced Hematological Toxicity
Authors: Li Juan , Chen Bing , Xi Wen‐Qi , Yang Chen , Zhang Wei‐Xia 
Published: May 2021

AbstractMost patients experience severe hematological toxicity during treatment with gemcitabine; thus, preventing such toxicity would improve the treatment effects and patient quality of life. We analyzed 13 polymorphisms in the transporters, metabolizing enzymes, targets, and genes involved in DNA damage and the folate pathway among 132 patients treated with gemcitabine and studied their association with the severity of the hematological toxicities. Single‐locus analysis showed that the single‐nucleotide polymorphisms (SNPs) RRM1 rs12806698 and rs11031918 and DCTD rs7663494 were significantly associated with severe neutropenia, hENT1 rs760370 and hCNT3 rs7867504 and rs4877831 were associated with severe leukopenia, CDA rs2072671, DCTD rs7663494, and WEE1 rs3910384 were associated with severe anemia, and MTHFR rs1801133 was associated with severe thrombocytopenia after stringent Bonferroni correction (P < .0038). The gene‐gene interaction analysis identified the overall best models, including a 2‐way interaction model (hCNT3 rs7867504 and dCK rs12648166) for severe leukopenia (P = .0022) and a 3‐locus model (CDA rs207671, DCTD rs7663494, and WEE1 rs3910384) for severe anemia with a strong synergistic effect (P = .0001). The association with hematological toxicity was further strengthened by the results of a haplotype analysis, in which the homozygous genotype combination of rs3910384 CC, rs2072671 AA, rs12648166 GG, rs7867504 CC, and rs7663494 TT conferred high genetic susceptibility to severe thrombocytopenia. Our results suggest that the gene‐gene interaction of gemcitabine metabolic pathway genes and WEE1 contributes to susceptibility to gemcitabine‐induced hematological toxicity. Moreover, we propose a promising data‐mining analysis approach (generalized multifactor dimensionality reduction) to detect and characterize gene‐gene interactions.
Gene expression profiling impacts treatment decision making in newly diagnosed multiple myeloma patients in the prospective PROMMIS trial
Authors: Biran Noa , Dhakal Binod , Lentzsch Suzanne , Siegel David , Usmani Saad Z. , Rossi Adriana , Rosenbaum Cara , Bhutani Divaya , Vesole David H. , Rodriguez Cesar , Nooka Ajay K. , van Rhee Frits , Stork‐Sloots Lisette , de Snoo Femke , Bhattacharyya Pritish K. , Dash Durga Prasad , Zümrütçü Sena , van Vliet Martin H. , Hari Parameswaran , Niesvizky Ruben 
Published: May 2021

AbstractMultiple myeloma (MM) is a heterogeneous hematologic malignancy associated with several risk factors including genetic aberrations which impact disease response and survival. Thorough risk classification is essential to select the best clinical strategy to optimize outcomes. The SKY92 molecular signature classifies patients as standard‐ or high‐risk for progression. The PRospective Observational Multiple Myeloma Impact Study (PROMMIS; NCT02911571) measures impact of SKY92 on risk classification and treatment plan. Newly diagnosed MM patients had bone marrow aspirates analyzed for SKY92. Physicians completed a questionnaire for each patient capturing risk classification, hypothetical treatment plan, and physician confidence in the treatment plan, before and after unblinding SKY92. One hundred forty seven MM patients were enrolled. Before unblinding SKY92, physicians regarded 74 (50%) patients as clinical standard‐risk. After unblinding SKY92, 16 patients were re‐assigned as high‐risk by the physician, and for 15 of them treatment strategy was impacted, resulting in an escalated treatment plan. For the 73 (50%) clinical high‐risk patients, SKY92 indicated 46 patients to be standard‐risk; for 31 of these patients the treatment strategy was impacted consistent with a de‐escalation of risk. Overall, SKY92 impacted treatment decisions in 37% of patients (p < 0.001). For clinical decision‐making, physicians incorporated SKY92, and the final assigned clinical risk was in line with SKY92 for 89% of patients. Furthermore, SKY92 significantly increased the confidence of the physicians’ treatment decisions (p < 0.001). This study shows potential added value of SKY92 in MM for treatment decision making.
Gut microbiota shape B cell in health and disease settings
Authors: Yu Baichao , Wang Luman , Chu Yiwei 
Published: May 2021

AbstractRecent accumulating evidence supports the hypothesis that the intricate interaction between gut microbiota and the immune system profoundly affects health and disease in humans and mice. In this context, microbiota plays an important role in educating and shaping the host immune system which, in turn, regulates gut microbiota diversity and function to maintain homeostasis. Studies have demonstrated that intestinal microbiota participates in shaping B cells in health and disease settings. Herein, we review the recent progress in understanding how microbiota regulates B-cell development, focusing on early-life B-cell repertoire generation in GALT and how microbial products, including microbial antigens and metabolites, affect B-cell activation and differentiation to ultimately regulate B-cell function. We also discuss the interaction between gut microbiota and B cells under pathogenic conditions and highlight new approaches that can be applied to treat various diseases.
SARS‐CoV‐2 prevalence and maternal‐perinatal outcomes among pregnant women admitted for delivery: Experience from COVID‐19‐dedicated maternity hospital in Jammu, Jammu and Kashmir (India)
Authors: Gupta Puneet , Kumar Surender , Sharma Shashi S. 
Published: May 2021

AbstractThe impact of SARS‐CoV‐2 infection in pregnant women and their neonates is an area of research interest nowadays. To date, there is limited knowledge about SARS‐CoV‐2 prevalence, maternal and perinatal outcomes of pregnant women at term in middle‐ and low‐income countries. In the present retro‐prospective study, medical records of pregnant women admitted for delivery were reviewed from the largest Covid‐19 dedicated Shri Maharaja Gulab Singh (SMGS) maternity hospital. The SARS‐CoV‐2 screening was carried out for all pregnant women admitted for delivery using RT‐PCR. All neonates born from SARS‐CoV‐2‐positive mothers were isolated and tested for SARS‐CoV‐2 infection. Most of the pregnant women (90.6%) were asymptomatic at the time of admission with a low prevalence (3.4%) of SARS‐CoV‐2. A higher rate of asymptomatic prevalence (86.1%) was found among SARS‐CoV‐2‐positive pregnant women. On the basis of the RT‐PCR result (negative vs. positive), statistically significant differences were found for maternal characteristics, such as mean gestational age (37.5 ± 2.2 vs. 36.6 ± 3.3), medical comorbidity (2.9% vs. 7.4%), and maternal outcomes like the C‐section rate (29.8% vs. 58.3%), preterm delivery (14.6% vs. 28.3), and neonatal outcomes like mean birth weight (2840 ± 450 vs. 2600 ± 600), low Apgar score (2.7% vs. 6.48%), and fetal distress (10.9% vs. 22.2%) among SARS‐CoV‐2 negative and positive cases, respectively. No neonate from SARS‐CoV‐2‐positive pregnant women was found to be positive for SARS‐CoV‐2 infection.
Prevalence and genotype distribution of JC polyomavirus in urine from patients with hematological malignancies in Vietnam
Authors: Bang Nguyen V. , Xuan Nguyen T. , Trung Ngo D. , Thu Nguyen T. , Nam Nguyen Q. , Hai Vu A. , Hang Dinh T. T. , Quyen Le T. B. , Thuong Luong T. H. , Lam Ngo Q. , Thong Nguyen H. , Phuong Nguyen M. , Linh Nguyen T. , Tu Hoang V. , Cuong Le M. , Su Hoang X. 
Published: May 2021

AbstractJC virus (JCV) causes progressive multifocal leukoencephalopathy in immunocompromised patients. The prevalence and genotype patterns of JCV vary between different geographical regions. This study was done to investigate the prevalence and genotype distribution of JCV in patients with hematological malignancies in Vietnam. A total of 48 urine samples were collected from patients with hematological malignancies. DNA was extracted and detection of JCV was by nested‐polymerase chain reaction. Sequence analysis was obtained and a phylogenetic tree was constructed for genotyping of JCV. Twenty‐seven (56.25%) urine samples tested positive for JCV. JCV genotype 7 was only observed in this study. Subtype analysis showed that JCV subtype 7A was the most commonly prevalent, followed by 7B1 and 7C1. Other subtypes were not detected in this population. There were no significant differences associated with age, gender, and biochemical parameters between patients with JCV and without JCV excretion in urine. The present study showed a high prevalence of JCV in the urine of patients with hematologic malignancies. The most common genotype found in this population was JCV subtype 7A.
Phylogenetic characteristics of HIV among female cross‐border travelers in Yunnan province between 2003 and 2012
Authors: Yang Ting , Liang Shuwen , Yang Shuting , Lin Yihan , Dian Ziqin , Zhao Ting , Su Hui , Zhang A‐mei , Liu Jingying , Huang Baoyang , Zhang Yifan , Xia Xueshan , Wang Binghui , Qin Weihong 
Published: May 2021

AbstractSexual transmission is currently the main mode of transmission of the human immunodeficiency virus (HIV). In this study, 181 HIV‐infected female cross‐border travelers entering Yunnan province were recruited between 2003 and 2012. HIV RNAs were extracted from their frozen serum and gag‐pol gene sequences were obtained for phylogenetic and recombination analyses. In total, 131 gag‐pol gene sequences were obtained successfully, at a rate of 72.4%. The most prevalent subtypes were CRF01_AE, followed by CRF08_BC, subtypes B and C. The other four subjects were classified as undefined subtypes and other recombinants. The subtype distribution of intravenous drug users was significantly different from that of sexually transmitted infections and unknown groups. The genetic distances of subtype B, C, and CRF01_AE strains were all close to the reference sequences from Yunnan province and Southeast Asian countries. Gene diversity and cocirculation of multiple subtypes were observed in female cross‐border travelers, and CRF01_AE was the dominant epidemic subtype. The advantages of these subtype preferences for sexual transmission were obvious in HIV infection and transmission among this population. Our findings also suggest that close attention should be given to the HIV infection status of the female migrant population. In addition, a description of their epidemic characteristics is significant for the surveillance and prevention of acquired immunodeficiency syndrome in the Yunnan province.
The influence of orbital parameters on the North American Monsoon system during the Last Interglacial Period
Authors: Insel Nadja , Berkelhammer Max 
Published: May 2021

ABSTRACTThe response of summer precipitation in the western United States to climate variability remains a subject of uncertainty. For example, palaeoclimate records indicate the North American Monsoon (NAM) was stronger and spatially more extensive during the Holocene, whereas recent modelling suggests a weakened NAM response to increasing temperatures. These illustrate diverging pictures of the NAM response to warming. Here, we examine summer precipitation in the southwestern US related to Last Interglacial insolation forcing. Using a high‐resolution climate model, we find that Eemian insolation forcing results in overall wetter conditions throughout most of the southwestern US, but significantly drier than present conditions over Arizona. The overall wetter conditions are associated with a northward shift of the anticyclonic circulation aloft and increased moisture in the lower and mid‐troposphere during the Eemian. Increased advection of Gulf of Mexico moisture is responsible for increasing precipitation in New Mexico and the northern edges of the NAM region. Drier conditions over Arizona are likely related to reduced local convection associated with reduced vertical moisture transport. These results highlight the spatial complexity of the NAM response to increasing radiative forcing and allow a better understanding of monsoon dynamics and variability in response to a warming climate.
Length of the Cricoid and Trachea in Children: Predicting Intubation Depth to Prevent Subglottic Stenosis
Authors: Propst Evan Jon , Gorodensky Jonah Haskel , Wolter Nikolaus Ernst 
Published: May 2021

ObjectiveDefine the length of the subglottis and trachea in children to predict a safe intubation depth.MethodsPatients <18 years undergoing rigid bronchoscopy from 2013 to 2020 were included. The carina and inferior borders of the cricoid and true vocal folds were marked on a bronchoscope and distances were measured. Patient age, weight, height, and chest height were recorded. Four styles of cuffed pediatric endotracheal tubes (ETT) were measured and potential positions of each cuff and tip were calculated within each trachea using five depth of intubation scenarios. Multivariate linear regression was performed to identify predictors of subglottic and tracheal length.ResultsMeasurements were obtained from 210 children (141 male, 69 female), mean (SD) age 3.21 (3.66) years. Patient height was the best predictor of subglottic length (R2: 0.418): Lengthsg (mm) = 0.058 * height (cm) + 2.8, and tracheal length (R2: 0.733): Lengtht (mm) = 0.485 * height (cm) + 21.3. None of the depth of intubation scenarios maintained a cuff‐free subglottis for all ETT styles investigated. A formula for depth of intubation: Lengthdi (mm) = 0.06 * height (cm) + 8.8 found that no ETT cuffs would be in the subglottis and all tips would be above the carina.ConclusionCurrent strategies for determining appropriate depth of intubation pose a high risk of subglottic ETT cuff placement. Placing the inferior border of the vocal cords 0.06 * height (cm) + 8.8 from the superior border of the inflated ETT cuff may prevent subglottic cuff placement and endobronchial intubation.Level of Evidence4 Laryngoscope, 132:S1–S10, 2022
Modeling Local Oscillatory Shear Dynamics of Functionalized Polymer Grafted Nanoparticles
Authors: Kadre Diksha , Iyer Balaji V. S. 
Published: May 2021

AbstractThis study examines local oscillatory shear dynamics of spherical polymer grafted nanoparticles (PGNs) composed of a rigid nanoparticle core of fixed radius, nm, and coronas of varying number of grafted polymer arms, . The grafted polymer arms are end‐functionalized such that the interacting PGNs form labile bonds when their coronas overlap. The effect of PGN structure on local dynamics is examined by imposing controlled oscillatory displacement on simple systems constructed using three identical interacting PGNs with bonded interactions under mechanical equilibrium. The displacement‐induced bond evolution between PGNs in this system is captured employing a master equation for determining probability of finding n bonds between PGNs as a function of oscillation frequency (). A multi‐component model combined with master equation approach is employed for modeling the effect of varying number of grafted arms ( and 1200) and strain amplitude () on the local shear response of the PGN system. The resulting shear response is analyzed using both linear and non‐linear rheological measures obtained using the Chebyshev polynomial framework. The rheological measures thus obtained are found to vary strongly with the number of grafted arms and strain amplitude.
Movement Disorders and Liver Disease
Authors: Mulroy Eoin , Baschieri Francesca , Magrinelli Francesca , Latorre Anna , Cortelli Pietro , Bhatia Kailash P. 
Published: May 2021

ABSTRACTThe association of movement disorders with structural or functional hepatic disease occurs in three principal scenarios: (1) combined involvement of both organ systems from a single disease entity, (2) nervous system dysfunction resulting from exposure to toxic compounds in the setting of defective hepatic clearance, or (3) hepatic and/or neurological injury secondary to exposure to exogenous drugs or toxins. An important early step in the workup of any patient with combined movement disorders and liver disease is the exclusion of Wilson's disease. Diagnostic delay remains common for this treatable disorder, and this has major implications for patient outcomes. Thereafter, a structured approach integrating variables such as age of onset, tempo of progression, nature and severity of liver involvement, movement disorder phenomenology, exposure to drugs/toxins and laboratory/neuroimaging findings is key to ensuring timely diagnosis and disease‐specific therapy. Herein, we provide an overview of disorders which may manifest with a combination of movement disorders and liver disease, structured under the three headings as detailed above. In each section, the most common disorders are discussed, along with important clinical pearls, suggested diagnostic workup, differential diagnoses and where appropriate, treatment considerations.
Analysis and numerical simulation of cross reaction–diffusion systems with the Caputo–Fabrizio and Riesz operators
Authors: Owolabi Kolade M. 
Published: May 2021

AbstractThe evolutionary dynamics of cross‐reaction–diffusion equations of predator–prey type are investigated in the sense of fractional operator. In the models, we replace the classical time and spatial derivatives with the Caputo–Fabrizio and Riesz fractional derivatives, respectively. The nature of the resulting problem (is nonlinear, nonlocal, and nonsingular) do not either admit a closed form solution, while in most cases the analytical solution is too involved to be useful. As a result, there is need to provide a reliable numerical scheme that can approximate these derivatives in time and space. Hence, we formulate an approximation scheme with second‐order convergence rate for the time‐Caputo–Fabrizio fractional operator of order 0 < α ≤ 1 and L1 formula for the Riesz fractional derivative of order 1 < β ≤ 2 in space. As a case study, we consider two examples of strongly coupled cross fractional reaction–diffusion systems describing the interaction between two individual species that prey on the other one. We examine the system for stability analysis and establish the condition for the occurrence of Turing instability. The complexity of the dynamics of time–space cross fractional reaction–diffusion systems is theoretically studied and numerically in one and two dimensions for some instances of fractional orders.
Mask R‐CNN‐based feature extraction and three‐dimensional recognition of rice panicle CT images
Authors: Kong Huihua , Chen Ping 
Published: May 2021

AbstractThe rice panicle seed setting rate is extremely important for calculating rice yield and performing genetic analysis. Unlike machine vision, X‐ray computed tomography (CT) imaging is a nondestructive technique that provides direct information on the internal and external structure of rice panicles. However, occlusion and adhesion of panicles and grains in a CT image sequence make these objects difficult to identify, which in turn hinders accurate determination of the seed setting rate of rice panicles. Therefore, this paper proposes a method based on a mask region convolutional neural network (Mask R‐CNN) for feature extraction and three‐dimensional (3‐D) recognition of CT images of rice panicles. X‐ray CT feature characterization was combined with the Mask R‐CNN algorithm to perform feature extraction and classification of a panicle and grains in each layer of the CT sequence. The Euclidean distance between adjacent layers was minimized to extract the features of a 3‐D panicle and grains. The results were used to calculate the rice panicle seed setting rate. The proposed method was experimentally verified using eight sets of different rice panicles. The results showed that the proposed method can efficiently identify and count plump grains and blighted grains to achieve an accuracy above 99% for the seed setting rate.
Tuning the glass transition of siloxane‐based poly(ionic liquid)s towards high ion conductivity
Authors: Reiter Manuel , Anton Arthur Markus , Chang Jian , Kremer Friedrich , Unterlass Miriam M. , Yuan Jiayin 
Published: May 2021

AbstractHerein, we report a simple and versatile synthetic approach towards siloxane‐based poly(ionic liquid)s (PILs) with unusually low glass transition temperatures (Tg) down to −73°C, and thus “liquid‐like” behavior at room temperature. We designed a polydimethylsiloxane‐derived copolymer carrying dialkylimidazolium moieties, and by careful selection of the side‐chain length and the type of anions we were able to manipulate its Tg over a wide range and reach high ionic conductivities (σDC) up to 4.8 × 10−5 S/cm at 300 K. The ionized species make up only a minor fraction (<25 mol%) of the overall repeating units and are supposedly randomly distributed: Yet our results indicate dramatic effects on the thermal properties due to repulsive interactions between ionic and non‐ionic segments.
AlphaFold2 predicts the inward‐facing conformation of the multidrug transporter LmrP
Authors: del Alamo Diego , Govaerts Cédric , Mchaourab Hassane S. 
Published: May 2021

AbstractAs part of the CASP competition, the protein structure prediction algorithm AlphaFold2 generated multiple models of the proton/drug antiporter LmrP. Previous distance restraints from double electron‐electron resonance spectroscopy, a technique which reports distance distributions between spin labels attached to proteins, suggest that one of the lower‐ranked models may have captured a conformation that has so far eluded experimental structure determination.
ACE2‐based decoy receptors for SARS coronavirus 2
Authors: Jing Wenyang , Procko Erik 
Published: May 2021

AbstractSARS coronavirus 2 is neutralized by proteins that block receptor‐binding sites on spikes that project from the viral envelope. In particular, substantial research investment has advanced monoclonal antibody therapies to the clinic where they have shown partial efficacy in reducing viral burden and hospitalization. An alternative is to use the host entry receptor, angiotensin‐converting enzyme 2 (ACE2), as a soluble decoy that broadly blocks SARS‐associated coronaviruses with limited potential for viral escape. Here, we summarize efforts to engineer higher affinity variants of soluble ACE2 that rival the potency of affinity‐matured antibodies. Strategies have also been used to increase the valency of ACE2 decoys for avid spike interactions and to improve pharmacokinetics via IgG fusions. Finally, the intrinsic catalytic activity of ACE2 for the turnover of the vasoconstrictor angiotensin II may directly address COVID‐19 symptoms and protect against lung and cardiovascular injury, conferring dual mechanisms of action unachievable by monoclonal antibodies. Soluble ACE2 derivatives therefore have the potential to be next generation therapeutics for addressing the immediate needs of the current pandemic and possible future outbreaks.