bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide unbalanced expression bias and expression level dominance toward Brassica oleracea in artificially synthesized intergeneric hybrids of Raphanobrassica
Authors: Zhang Libin , He Jianjie , He Hongsheng , Wu Jiangsheng , Li Maoteng 
Published: December 2021

AbstractRaphanobrassica(RrRrCrCr, 2n = 4x = 36), which is generated by distant hybridization between the maternal parentRaphanus sativus(RsRs, 2n = 2x = 18) and the paternal parentBrassica oleracea(C°C°, 2n = 2x = 18), displays intermediate silique phenotypes compared to diploid progenitors. However, the hybrid shares much more similarities in silique phenotypes with those ofB. oleraceathan those ofR. sativus. Strikingly, the silique ofRaphanobrassicais obviously split into two parts. To investigate the gene expression patterns behind these phenomena, transcriptome analysis was performed on the upper, middle, and lower sections of pods (RCsiu, RCsim, and RCsil), seeds in the upper and lower sections of siliques (RCseu and RCsel) fromRaphanobrassica, whole pods (Rsi and Csi) and all seeds in the siliques (Rse and Cse) fromR. sativusandB. oleracea. Transcriptome shock was observed in all five aforementioned tissues ofRaphanobrassica. Genome-wide unbalanced biased expression and expression level dominance were also discovered, and both of them were towardB. oleraceainRaphanobrassica, which is consistent with the observed phenotypes. The present results reveal the global gene expression patterns of different sections of siliques ofRaphanobrassica, pods, and seeds ofB. oleraceaandR. sativus, unraveling the tight correlation between global gene expression patterns and phenotypes of the hybrid and its parents.
Augmenting zero-Kelvin quantum mechanics with machine learning for the prediction of chemical reactions at high temperatures
Authors: Garrido Torres Jose Antonio , Gharakhanyan Vahe , Artrith Nongnuch , Eegholm Tobias Hoffmann , Urban Alexander 
Published: December 2021

AbstractThe prediction of temperature effects from first principles is computationally demanding and typically too approximate for the engineering of high-temperature processes. Here, we introduce a hybrid approach combining zero-Kelvin first-principles calculations with a Gaussian process regression model trained on temperature-dependent reaction free energies. We apply this physics-based machine-learning model to the prediction of metal oxide reduction temperatures in high-temperature smelting processes that are commonly used for the extraction of metals from their ores and from electronics waste and have a significant impact on the global energy economy and greenhouse gas emissions. The hybrid model predicts accurate reduction temperatures of unseen oxides, is computationally efficient, and surpasses in accuracy computationally much more demanding first-principles simulations that explicitly include temperature effects. The approach provides a general paradigm for capturing the temperature dependence of reaction free energies and derived thermodynamic properties when limited experimental reference data is available.
Comprehensive targeting of resistance to inhibition of RTK signaling pathways by using glucocorticoids
Authors: Gong Ke , Guo Gao , Beckley Nicole A. , Yang Xiaoyao , Zhang Yue , Gerber David E. , Minna John D. , Burma Sandeep , Zhao Dawen , Akbay Esra A. , Habib Amyn A. 
Published: December 2021

AbstractInhibition of RTK pathways in cancer triggers an adaptive response that promotes therapeutic resistance. Because the adaptive response is multifaceted, the optimal approach to blunting it remains undetermined. TNF upregulation is a biologically significant response to EGFR inhibition in NSCLC. Here, we compared a specific TNF inhibitor (etanercept) to thalidomide and prednisone, two drugs that block TNF and also other inflammatory pathways. Prednisone is significantly more effective in suppressing EGFR inhibition-induced inflammatory signals. Remarkably, prednisone induces a shutdown of bypass RTK signaling and inhibits key resistance signals such as STAT3, YAP and TNF-NF-κB. Combined with EGFR inhibition, prednisone is significantly superior to etanercept or thalidomide in durably suppressing tumor growth in multiple mouse models, indicating that a broad suppression of adaptive signals is more effective than blocking a single component. We identify prednisone as a drug that can effectively inhibit adaptive resistance with acceptable toxicity in NSCLC and other cancers.
SPEN is required for Xist upregulation during initiation of X chromosome inactivation
Authors: Robert-Finestra Teresa , Tan Beatrice F. , Mira-Bontenbal Hegias , Timmers Erika , Gontan Cristina , Merzouk Sarra , Giaimo Benedetto Daniele , Dossin François , van IJcken Wilfred F. J. , Martens John W. M. , Borggrefe Tilman , Heard Edith , Gribnau Joost 
Published: December 2021

AbstractAt initiation of X chromosome inactivation (XCI), Xist is monoallelically upregulated from the future inactive X (Xi) chromosome, overcoming repression by its antisense transcript Tsix. Xist recruits various chromatin remodelers, amongst them SPEN, which are involved in silencing of X-linked genes in cis and establishment of the Xi. Here, we show that SPEN plays an important role in initiation of XCI. Spen null female mouse embryonic stem cells (ESCs) are defective in Xist upregulation upon differentiation. We find that Xist-mediated SPEN recruitment to the Xi chromosome happens very early in XCI, and that SPEN-mediated silencing of the Tsix promoter is required for Xist upregulation. Accordingly, failed Xist upregulation in Spen−/− ESCs can be rescued by concomitant removal of Tsix. These findings indicate that SPEN is not only required for the establishment of the Xi, but is also crucial in initiation of the XCI process.
Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair
Authors: Yan Chunli , Dodd Thomas , Yu Jina , Leung Bernice , Xu Jun , Oh Juntaek , Wang Dong , Ivanov Ivaylo 
Published: December 2021

AbstractTranscription-coupled repair is essential for the removal of DNA lesions from the transcribed genome. The pathway is initiated by CSB protein binding to stalled RNA polymerase II. Mutations impairing CSB function cause severe genetic disease. Yet, the ATP-dependent mechanism by which CSB powers RNA polymerase to bypass certain lesions while triggering excision of others is incompletely understood. Here we build structural models of RNA polymerase II bound to the yeast CSB ortholog Rad26 in nucleotide-free and bound states. This enables simulations and graph-theoretical analyses to define partitioning of this complex into dynamic communities and delineate how its structural elements function together to remodel DNA. We identify an allosteric pathway coupling motions of the Rad26 ATPase modules to changes in RNA polymerase and DNA to unveil a structural mechanism for CSB-assisted progression past less bulky lesions. Our models allow functional interpretation of the effects of Cockayne syndrome disease mutations.
Mounting, structure and autocleavage of a type VI secretion-associated Rhs polymorphic toxin
Authors: Jurėnas Dukas , Rosa Leonardo Talachia , Rey Martial , Chamot-Rooke Julia , Fronzes Rémi , Cascales Eric 
Published: December 2021

AbstractBacteria have evolved toxins to outcompete other bacteria or to hijack host cell pathways. One broad family of bacterial polymorphic toxins gathers multidomain proteins with a modular organization, comprising a C-terminal toxin domain fused to a N-terminal domain that adapts to the delivery apparatus. Polymorphic toxins include bacteriocins, contact-dependent growth inhibition systems, and specialized Hcp, VgrG, PAAR or Rhs Type VI secretion (T6SS) components. We recently described and characterized Tre23, a toxin domain fused to a T6SS-associated Rhs protein in Photorhabdus laumondii, Rhs1. Here, we show that Rhs1 forms a complex with the T6SS spike protein VgrG and the EagR chaperone. Using truncation derivatives and cross-linking mass spectrometry, we demonstrate that VgrG-EagR-Rhs1 complex formation requires the VgrG C-terminal β-helix and the Rhs1 N-terminal region. We then report the cryo-electron-microscopy structure of the Rhs1-EagR complex, demonstrating that the Rhs1 central region forms a β-barrel cage-like structure that encapsulates the C-terminal toxin domain, and provide evidence for processing of the Rhs1 protein through aspartyl autoproteolysis. We propose a model for Rhs1 loading on the T6SS, transport and delivery into the target cell.
An immunodominant NP105–113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease
Authors: Peng Yanchun , Felce Suet Ling , Dong Danning , Penkava Frank , Mentzer Alexander J. , Yao Xuan , Liu Guihai , Yin Zixi , Chen Ji-Li , Lu Yongxu , Wellington Dannielle , Wing Peter A. C. , Dominey-Foy Delaney C. C. , Jin Chen , Wang Wenbo , Hamid Megat Abd , Fernandes Ricardo A. , Wang Beibei , Fries Anastasia , Zhuang Xiaodong , Ashley Neil , Rostron Timothy , Waugh Craig , Sopp Paul , Hublitz Philip , Beveridge Ryan , Tan Tiong Kit , Dold Christina , Kwok Andrew J. , Rich-Griffin Charlotte , Dejnirattisa Wanwisa , Liu Chang , Kurupati Prathiba , Nassiri Isar , Watson Robert A. , Tong Orion , Taylor Chelsea A. , Kumar Sharma Piyush , Sun Bo , Curion Fabiola , Revale Santiago , Garner Lucy C. , Jansen Kathrin , Ferreira Ricardo C. , Attar Moustafa , Fry Jeremy W. , Russell Rebecca A. ,   COMBAT Consortium, Stauss Hans J. , James William , Townsend Alain , Ho Ling-Pei , Klenerman Paul , Mongkolsapaya Juthathip , Screaton Gavin R. , Dendrou Calliope , Sansom Stephen N. , Bashford-Rogers Rachael , Chain Benny , Smith Geoffrey L. , McKeating Jane A. , Fairfax Benjamin P. , Bowness Paul , McMichael Andrew J. , Ogg Graham , Knight Julian C. , Dong Tao 
Published: December 2021

AbstractNP105–113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105–113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105–113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105–113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105–113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.
Significance low oscillating magnetic field and Hall current in the nano-ferrofluid flow past a rotating stretchable disk
Authors: Ramzan Muhammad , Riasat Saima , Zhang Yan , Nisar Kottakkaran Sooppy , Badruddin Irfan Anjum , Ahammad N. Ameer , Ghazwani Hassan Ali S. 
Published: December 2021

AbstractThe present investigation involves the Hall current effects past a low oscillating stretchable rotating disk with Joule heating and the viscous dissipation impacts on a Ferro-nanofluid flow. The entropy generation analysis is carried out to study the impact of rotational viscosity by applying a low oscillating magnetic field. The model gives the continuity, momentum, temperature, magnetization, and rotational partial differential equations. These equations are transformed into the ODEs and solved by using bvp4c MATLAB. The graphical representation of arising parameters such as effective magnetization and nanoparticle concentration on thermal profile, velocity profile, and rate of disorder along with Bejan number is presented. Drag force and the heat transfer rate are given in the tabular form. It is comprehended that for increasing nanoparticle volume fraction and magnetization parameter, the radial, and tangential velocity reduce while thermal profile surges. The comparison of present results for radial and axial velocity profiles with the existing literature shows approximately the same results.
Long-term specific IgG response to SARS-CoV-2 nucleocapsid protein in recovered COVID-19 patients
Authors: Chansaenroj Jira , Yorsaeng Ritthideach , Posuwan Nawarat , Puenpa Jiratchaya , Wanlapakorn Nasamon , Sudhinaraset Natthinee , Sripramote Manit , Chalongviriyalert Piti , Jirajariyavej Supunee , Kiatpanabhikul Phatharaporn , Saiyarin Jatuporn , Soudon Chulikorn , Thienfaidee Orawan , Palakawong Na Ayuthaya Thitisan , Brukesawan Chantapat , Chirathaworn Chintana , Intharasongkroh Duangnapa , Chaiwanichsiri Dootchai , Issarasongkhram Mila , Kitphati Rungrueng , Mungaomklang Anek , Nagavajara Pijaya , Poovorawan Yong 
Published: December 2021

AbstractThis study monitored the long-term immune response to severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in patients who had recovered from coronavirus disease (COVID)-19. Anti-nucleocapsid immunoglobulin G (anti-N IgG) titer in serum samples collected at a single (N = 302) or multiple time points (N = 229) 3–12 months after COVID-19 symptom onset or SARS-CoV-2 detection in respiratory specimens was measured by semiquantitative chemiluminescent microparticle immunoassay. The 531 patients (966 specimens) were classified according to the presence or absence of pneumonia symptoms. Anti N IgG was detected in 87.5% of patients (328/375) at 3 months, 38.6% (93/241) at 6 months, 23.7% (49/207) at 9 months, and 26.6% (38/143) at 12 months. The anti-N IgG seropositivity rate was significantly lower at 6, 9, and 12 months than at 3 months (P < 0.01) and was higher in the pneumonia group than in the non-pneumonia/asymptomatic group at 6 months (P < 0.01), 9 months (P = 0.04), and 12 months (P = 0.04). The rate started to decline 6–12 months after symptom onset. Anti-N IgG sample/cutoff index was positively correlated with age (r = 0.192, P < 0.01) but negatively correlated with interval between symptom onset and blood sampling (r =  − 0.567, P < 0.01). These findings can guide vaccine strategies in recovered COVID-19 patients.
A retrospective HEART risk score comparation of acute non-traumatic chest pain patients in an emergency department in Spain
Authors: San Román Arispe Iris Nathalie , Marsal Mora Josep Ramón , Yuguero Torres Oriol , Bravo Marta Ortega 
Published: December 2021

AbstractNon traumatic chest pain is the second most common cause of attention at the Emergency Departments (ED). The objective is to compare the effectiveness of HEART risk score and the risk of having a Major Adverse Cardiovascular Event (MACE) during the following 6 weeks in ‘Acute Non-traumatic Chest Pain’ (ANTCP) patients of an ED in Lleida (Spain). The ANTCP patient cohort was defined using medical data from January 2015 to January 2016. A retrospective study was performed among 300 ANTCP patients. Diagnostic accuracy to predict MACE, HEART risk score effectiveness and patient risk stratification were analysed on the ANTCP Cohort. HEART risk score was conducted on ANTCP Cohort data and patients were stratified as low-risk (n = 116, 38.7%), moderate-risk (n = 164, 54.7%) and high-risk (n = 20, 6.7%); differently from the assessment performed by 'Current Emergency Department Guidelines’ (CEDG) on the same patients: low risk and discharge (n = 56, 18.7%), medium risk and need of complementary tests (n = 137, 45.7%) and high risk and hospital admission (n = 107, 35.7%).The incidence of MACE was 2.5%, 20.7% and 100% in low, moderate and high-risk, respectively. Discrimination and accuracy indexes were moderate (AUC = 0.73, 95% confidence interval: 0.67–0.80). Clustering moderate-high risk groups by MACE incidence showed an 89.5% of sensitivity. Data obtained from this study suggests that HEART risk score stratified better ‘acute non-traumatic chest pain’ (ANTCP) patients in an Emergency Department (ED) compared with ‘Current Emergency Department Guidelines’ (CEDG) at the Hospital Universitari Arnau de Vilanova (HUAV). HEART score would reduce the number of subsequent consultations, unnecessary admissions and complementary tests.Trial registration: Retrospectively registered.
Leg length measures appear inaccurate in the early phase following total hip arthroplasty
Authors: Smolle Maria Anna , Fischerauer Stefan Franz , Maier Michael , Reinbacher Patrick , Friesenbichler Jörg , Ruckenstuhl Paul , Grandesso Maria , Leithner Andreas , Maurer-Ertl Werner 
Published: December 2021

AbstractThe aims of this study were to (1) assess reliability of leg length discrepancy (LLD) measurements at different anatomical landmarks, (2) longitudinally investigate LLD in patients within the first year following total hip arthroplasty (THA) and to (3) correlate changes in LLD with functional outcome. Ninety-nine patients with short stem THA (53.3% males, mean age: 61.0 ± 8.1 years) were prospectively included. Upright pelvic anteroposterior (a.p.) radiographs taken at 6 timepoints (preoperatively, discharge, 6, 12, 24, 52 weeks postoperatively) were used to assess LLD at 5 anatomical landmarks (iliac crest, upper sacroiliac joint, lower sacroiliac joint, tear drop figure, greater trochanter). WOMAC and Harris Hip Score (HHS) were obtained preoperatively and at 6 and 52 weeks. LLD measures significantly increased in the initial phase following THA, from discharge to 6 weeks postoperatively and remained constant thereafter. Documentation of LLDs is dependent on measurement site: LLDs varied significantly between trochanter and iliac crest to tear drop figure (p < 0.001). Functional assessments did not correlate with the occurrence of LLDs [WOMAC (p = 0.252); HHS (p = 0.798)]. Radiographic assessment of LLD following THA may not be performed early postoperatively, as measurements appear to inaccurately reflect actual LLDs at this time, potentially due incomplete leg extension and/or inhibited weight-bearing.
A comprehensive in silico investigation into the nsSNPs of Drd2 gene predicts significant functional consequences in dopamine signaling and pharmacotherapy
Authors: Lira Samia Sultana , Ahammad Ishtiaque 
Published: December 2021

AbstractDRD2 is a neuronal cell surface protein involved in brain development and function. Variations in the Drd2 gene have clinical significance since DRD2 is a pharmacotherapeutic target for treating psychiatric disorders like ADHD and schizophrenia. Despite numerous studies on the disease association of single nucleotide polymorphisms (SNPs) in the intronic regions, investigation into the coding regions is surprisingly limited. In this study, we aimed at identifying potential functionally and pharmaco-therapeutically deleterious non-synonymous SNPs of Drd2. A wide array of bioinformatics tools was used to evaluate the impact of nsSNPs on protein structure and functionality. Out of 260 nsSNPs retrieved from the dbSNP database, initially 9 were predicted as deleterious by 15 tools. Upon further assessment of their domain association, conservation profile, homology models and inter-atomic interaction, the mutant F389V was considered as the most impactful. In-depth analysis of F389V through Molecular Docking and Dynamics Simulation revealed a decline in affinity for its native agonist dopamine and an increase in affinity for the antipsychotic drug risperidone. Remarkable alterations in binding interactions and stability of the protein–ligand complex in simulated physiological conditions were also noted. These findings will improve our understanding of the consequence of nsSNPs in disease-susceptibility and therapeutic efficacy.
Fast-velocity Resistance Training Improves Force Development and
Mobility in Multiple Sclerosis
Authors: Andreu-Caravaca Luis , Ramos-Campo Domingo Jesús , Chung Linda H. , Manonelles Pedro , Boas Joao Paulo Vilas , Rubio-Arias Jacobo Ángel 
Published: December 2021

AbstractThis study aimed to analyze the benefits of a lower-limb fast-velocity concentric
resistance training on rate of force development, mobility, and quality of life
in people with Multiple Sclerosis. A randomized controlled trial was conducted
in 30 people with Multiple Sclerosis, who were randomly assigned to either an
experimental (n=18) or a control (n=12) group. The experimental
group carried out 10-weeks of fast-velocity concentric resistance training,
while the control group did not perform any intervention. Early and late rate of
force development during knee extension in both legs, sit-to-stand and Timed Up
and Go tests and quality life questionnaire were evaluated before and after
intervention. The training program evoked an increase in early rate of force
development in experimental group (0–30; Rightleg:
63.9%, p<0.001; ES=-1.4; Leftleg:
52.7%, p<0.001; ES=-1.0) compared to control group
(showed modest increases). Furthermore, experimental group improved mobility
after training (Sit-to-stand: 22.2%, p<0.001; ES=1.0;
Timed Up and Go Test: 10.1%, p<0.001; ES=1.1) and
increased the perception of quality of life after training, while control showed
no changes. The fast-velocity concentric resistance training has the potential
to improve early rate of force development and mobility after 10-weeks of
training. In addition, the increase in self-perceived quality of life following
this training modality demonstrates promising results in the Multiple Sclerosis
population.
Laparoscopic-Assisted Anorectoplasty for Rectovestibular Fistula: A Comparison Study with Anterior Sagittal Anorectoplasty
Authors: Zhou Yan , Xu Hang , Ming Anxiao , Diao Mei , Sun Hailin , Xie Xianghui , Li Long 
Published: December 2021

Abstract
Background Posterior or anterior sagittal anorectoplasty (ASARP) is the mainstream for correcting rectovestibular fistula (RVF). However, the intermediate RVF has the potential risk of wound complications when applying ASARP due to its high rectal pouch, long fistula tract, and difficulty separating the rectum and vagina. We developed laparoscopic-assisted anorectoplasty (LAARP) for surgical correction of RVF, which has acceptable preliminary outcomes. The purpose of this study is to evaluate the safety and efficacy of LAARP in comparison with ASARP for patients with RVF.
Materials and Methods Twenty-five patients with RVF who underwent LAARP between October 2017 and December 2020 were retrospectively reviewed. The outcomes were compared with 43 patients who underwent ASARP between April 2015 and August 2018. The age, weight at operation, sacral ratio, operative time, and postoperative hospital stay were evaluated. The results were assessed for complications, perineum appearance, and bowel function.
Results The two groups were comparable in terms of demographics. The median operative time of the LAARP group was significantly longer than that of the ASARP group (113 vs. 95 minutes; p = 0.015). The mean length of the resected rectum in the LAARP group was also longer than that in the ASARP group (6.75 ± 5.07 vs. 3.31 ± 3.06 cm; p = 0.001). Compared with the LAARP group, complications in the ASARP group were more frequent (4.0 vs. 27.9%, p = 0.036). No intraoperative or postoperative wound-related complications occurred in the LAARP group. However, in the ASARP group, one patient had an intraoperative vaginal injury and four had postoperative anastomosis-related complications. The incidence of redo operation in the ASARP group was significantly higher than that in the LAARP group (p = 0.000). Cosmetic satisfaction was higher in the LAARP group (96.0 vs. 76.7%; p < 0.05). In terms of voluntary bowel movement, soiling, and constipation, the LAARP group had similar results compare with the ASARP group.
Conclusion The LAARP technique has shown several unique strengths in treating intermediate type RVF, including lower risks of complications, and minimal muscular injury, with a comparable bowel function.