bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early alveolar macrophage response and IL-1R-dependent T cell priming determine transmissibility of Mycobacterium tuberculosis strains
Authors: Lovey Arianne , Verma Sheetal , Kaipilyawar Vaishnavi , Ribeiro-Rodrigues Rodrigo , Husain Seema , Palaci Moises , Dietze Reynaldo , Ma Shuyi , Morrison Robert D. , Sherman David. R. , Ellner Jerrold J. , Salgame Padmini 
Published: February 2022

AbstractMechanisms underlying variability in transmission of Mycobacterium tuberculosis strains remain undefined. By characterizing high and low transmission strains of M.tuberculosis in mice, we show here that high transmission M.tuberculosis strain induce rapid IL-1R-dependent alveolar macrophage migration from the alveolar space into the interstitium and that this action is key to subsequent temporal events of early dissemination of bacteria to the lymph nodes, Th1 priming, granulomatous response and bacterial control. In contrast, IL-1R-dependent alveolar macrophage migration and early dissemination of bacteria to lymph nodes is significantly impeded in infection with low transmission M.tuberculosis strain; these events promote the development of Th17 immunity, fostering neutrophilic inflammation and increased bacterial replication. Our results suggest that by inducing granulomas with the potential to develop into cavitary lesions that aids bacterial escape into the airways, high transmission M.tuberculosis strain is poised for greater transmissibility. These findings implicate bacterial heterogeneity as an important modifier of TB disease manifestations and transmission.
Disuse-associated loss of the protease LONP1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength
Authors: Xu Zhisheng , Fu Tingting , Guo Qiqi , Zhou Danxia , Sun Wanping , Zhou Zheng , Chen Xinyi , Zhang Jingzi , Liu Lin , Xiao Liwei , Yin Yujing , Jia Yuhuan , Pang Erkai , Chen Yuncong , Pan Xin , Fang Lei , Zhu Min-sheng , Fei Wenyong , Lu Bin , Gan Zhenji 
Published: February 2022

AbstractMitochondrial proteolysis is an evolutionarily conserved quality-control mechanism to maintain proper mitochondrial integrity and function. However, the physiological relevance of stress-induced impaired mitochondrial protein quality remains unclear. Here, we demonstrate that LONP1, a major mitochondrial protease resides in the matrix, plays a role in controlling mitochondrial function as well as skeletal muscle mass and strength in response to muscle disuse. In humans and mice, disuse-related muscle loss is associated with decreased mitochondrial LONP1 protein. Skeletal muscle-specific ablation of LONP1 in mice resulted in impaired mitochondrial protein turnover, leading to mitochondrial dysfunction. This caused reduced muscle fiber size and strength. Mechanistically, aberrant accumulation of mitochondrial-retained protein in muscle upon loss of LONP1 induces the activation of autophagy-lysosome degradation program of muscle loss. Overexpressing a mitochondrial-retained mutant ornithine transcarbamylase (ΔOTC), a known protein degraded by LONP1, in skeletal muscle induces mitochondrial dysfunction, autophagy activation, and cause muscle loss and weakness. Thus, these findings reveal a role of LONP1-dependent mitochondrial protein quality-control in safeguarding mitochondrial function and preserving skeletal muscle mass and strength, and unravel a link between mitochondrial protein quality and muscle mass maintenance during muscle disuse.
Non-thermal plasma-assisted rapid hydrogenolysis of polystyrene to high yield ethylene
Authors: Yao Libo , King Jaelynne , Wu Dezhen , Ma Jiayang , Li Jialu , Xie Rongxuan , Chuang Steven S. C. , Miyoshi Toshikazu , Peng Zhenmeng 
Published: February 2022

AbstractThe evergrowing plastic production and the caused concerns of plastic waste accumulation have stimulated the need for waste plastic chemical recycling/valorization. Current methods suffer from harsh reaction conditions and long reaction time. Herein we demonstrate a non-thermal plasma-assisted method for rapid hydrogenolysis of polystyrene (PS) at ambient temperature and atmospheric pressure, generating high yield (>40 wt%) of C1–C3 hydrocarbons and ethylene being the dominant gas product (Selectivity of ethylene, SC2H4 > 70%) within ~10 min. The fast reaction kinetics is attributed to highly active hydrogen plasma, which can effectively break bonds in polymer and initiate hydrogenolysis under mild condition. Efficient hydrogenolysis of post-consumer PS materials using this method is also demonstrated, suggesting a promising approach for fast retrieval of small molecular hydrocarbon modules from plastic materials as well as a good capability to process waste plastics in complicated conditions.
Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial
Authors: Barroso-Sousa Romualdo , Tarantino Paolo , Tayob Nabihah , Dang Chau , Yardley Denise A. , Isakoff Steven J. , Valero Vicente , Faggen Meredith , Mulvey Therese , Bose Ron , Hu Jiani , Weckstein Douglas , Wolff Antonio C. , Reeder-Hayes Katherine , Rugo Hope S. , Ramaswamy Bhuvaneswari , Zuckerman Dan , Hart Lowell , Gadi Vijayakrishna K. , Constantine Michael , Cheng Kit , Briccetti Frederick , Schneider Bryan , Garrett Audrey Merrill , Marcom Kelly , Albain Kathy , DeFusco Patricia , Tung Nadine , Ardman Blair , Nanda Rita , Jankowitz Rachel C. , Rimawi Mothaffar , Abramson Vandana , Pohlmann Paula R. , Van Poznak Catherine , Forero-Torres Andres , Liu Minetta , Ruddy Kathryn J. , Zheng Yue , Rosenberg Shoshana M. , Gelber Richard D. , Trippa Lorenzo , Barry William , DeMeo Michelle , Burstein Harold , Partridge Ann , Winer Eric P. , Krop Ian , Tolaney Sara M. 
Published: February 2022

AbstractThe excellent outcomes seen in patients treated with adjuvant trastuzumab emtansine (T-DM1) in the ATEMPT trial and the favorable toxicity profile associated with this agent make T-DM1 a potential therapeutic option for select patients with stage I HER2-positive breast cancer. Moreover, T-DM1 is an established adjuvant treatment for patients with HER2-positive breast cancer with the residual invasive disease after neoadjuvant therapy. Given that cardiotoxicity is the most significant adverse event of trastuzumab, which is a main molecular component of T-DM1, we conducted a sub-analysis of the ATEMPT trial to determine the cardiac safety of adjuvant T-DM1. In this analysis, the incidence of grade 3–4 left ventricular systolic dysfunction (LVSD) in T-DM1 or trastuzumab plus paclitaxel arms were respectively 0.8 and 1.8%. In addition, three (0.8%) patients in the T-DM1 arm and six (5.3%) patients in the adjuvant paclitaxel with trastuzumab (TH) arm experienced a significant asymptomatic left ventricular ejection fraction (LVEF) decline that per-protocol required holding T-DM1 or trastuzumab. All patients with available follow-up data experienced full resolution of cardiac symptoms and LVEF normalization. Furthermore, we performed an exploratory analysis to assess the relationship between age, baseline LVEF, and body mass index with cardiac outcomes. No significant association between these baseline characteristics and the incidence of significant asymptomatic LVEF decline or symptomatic LVSD was identified. The low incidence of significant cardiac adverse events in this population during therapy with adjuvant T-DM1 suggests that studies on the cost-effectiveness of cardiac monitoring during adjuvant therapy using anthracycline-free regimens are needed.Clinical Trial Registration:ClinicalTrials.gov, NCT01853748
Visualizing protein breathing motions associated with aromatic ring flipping
Authors: Mariño Pérez Laura , Ielasi Francesco S. , Bessa Luiza M. , Maurin Damien , Kragelj Jaka , Blackledge Martin , Salvi Nicola , Bouvignies Guillaume , Palencia Andrés , Jensen Malene Ringkjøbing 
Published: February 2022

AbstractAromatic residues cluster in the core of folded proteins, where they stabilize the structure through multiple interactions. Nuclear magnetic resonance (NMR) studies in the 1970s showed that aromatic side chains can undergo ring flips—that is, 180° rotations—despite their role in maintaining the protein fold1–3. It was suggested that large-scale ‘breathing’ motions of the surrounding protein environment would be necessary to accommodate these ring flipping events1. However, the structural details of these motions have remained unclear. Here we uncover the structural rearrangements that accompany ring flipping of a buried tyrosine residue in an SH3 domain. Using NMR, we show that the tyrosine side chain flips to a low-populated, minor state and, through a proteome-wide sequence analysis, we design mutants that stabilize this state, which allows us to capture its high-resolution structure by X-ray crystallography. A void volume is generated around the tyrosine ring during the structural transition between the major and minor state, and this allows fast flipping to take place. Our results provide structural insights into the protein breathing motions that are associated with ring flipping. More generally, our study has implications for protein design and structure prediction by showing how the local protein environment influences amino acid side chain conformations and vice versa.
Twin study reveals non-heritable immune perturbations in multiple sclerosis
Authors: Ingelfinger Florian , Gerdes Lisa Ann , Kavaka Vladyslav , Krishnarajah Sinduya , Friebel Ekaterina , Galli Edoardo , Zwicky Pascale , Furrer Reinhard , Peukert Christian , Dutertre Charles-Antoine , Eglseer Klara Magdalena , Ginhoux Florent , Flierl-Hecht Andrea , Kümpfel Tania , De Feo Donatella , Schreiner Bettina , Mundt Sarah , Kerschensteiner Martin , Hohlfeld Reinhard , Beltrán Eduardo , Becher Burkhard 
Published: February 2022

AbstractMultiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system underpinned by partially understood genetic risk factors and environmental triggers and their undefined interactions1,2. Here we investigated the peripheral immune signatures of 61 monozygotic twin pairs discordant for MS to dissect the influence of genetic predisposition and environmental factors. Using complementary multimodal high-throughput and high-dimensional single-cell technologies in conjunction with data-driven computational tools, we identified an inflammatory shift in a monocyte cluster of twins with MS, coupled with the emergence of a population of IL-2 hyper-responsive transitional naive helper T cells as MS-related immune alterations. By integrating data on the immune profiles of healthy monozygotic and dizygotic twin pairs, we estimated the variance in CD25 expression by helper T cells displaying a naive phenotype to be largely driven by genetic and shared early environmental influences. Nonetheless, the expanding helper T cells of twins with MS, which were also elevated in non-twin patients with MS, emerged independent of the individual genetic makeup. These cells expressed central nervous system-homing receptors, exhibited a dysregulated CD25–IL-2 axis, and their proliferative capacity positively correlated with MS severity. Together, our matched-pair analysis of the extended twin approach allowed us to discern genetically and environmentally determined features of an MS-associated immune signature.
Effects of field enhanced charge transfer on the luminescence properties of Si/SiO2 superlattices
Authors: Yazicioglu Deniz , Gutsch Sebastian , Zacharias Margit 
Published: February 2022

AbstractThe effect of an externally applied electric field on exciton splitting and carrier transport was studied on 3.5 nm Si nanocrystals embedded in SiO2superlattices with barrier oxide thicknesses varied between 2 and 4 nm. Through a series of photoluminescence measurements performed at both room temperature and with liquid N2cooling, it was shown that the application of an electric field resulted in a reduction of luminescence intensity due to exciton splitting and charging of nanocrystals within the superlattices. This effect was found to be enhanced when surface defects at the Si/SiO2interface were not passivated by H2treatment and severely reduced for inter layer barrier oxide thicknesses above 3 nm. The findings point to the surface defects assisting in carrier transport, lowering the energy required for exciton splitting. Said enhancement was found to be diminished at low temperatures due to the freezing-in of phonons. We propose potential device design parameters for photon detection and tandem solar cell applications utilizing the quantum confinement effect based on the findings of the present study.
Conserved topology of virus glycoepitopes presents novel targets for repurposing HIV antibody 2G12
Authors: Miller Nathaniel L. , Subramanian Vidya , Clark Thomas , Raman Rahul , Sasisekharan Ram 
Published: February 2022

AbstractComplex glycans decorate viral surface proteins and play a critical role in virus–host interactions. Viral surface glycans shield vulnerable protein epitopes from host immunity yet can also present distinct “glycoepitopes” that can be targeted by host antibodies such as the potent anti-HIV antibody 2G12 that binds high-mannose glycans on gp120. Two recent publications demonstrate 2G12 binding to high mannose glycans on SARS-CoV-2 and select Influenza A (Flu) H3N2 viruses. Previously, our lab observed 2G12 binding and functional inhibition of a range of Flu viruses that include H3N2 and H1N1 lineages. In this manuscript, we present these data alongside structural analyses to offer an expanded picture of 2G12-Flu interactions. Further, based on the remarkable breadth of 2G12 N-glycan recognition and the structural factors promoting glycoprotein oligomannosylation, we hypothesize that 2G12 glycoepitopes can be defined from protein structure alone according to N-glycan site topology. We develop a model describing 2G12 glycoepitopes based on N-glycan site topology, and apply the model to identify viruses within the Protein Data Bank presenting putative 2G12 glycoepitopes for 2G12 repurposing toward analytical, diagnostic, and therapeutic applications.
Dietary carbohydrate and the risk of type 2 diabetes: an updated systematic review and dose–response meta-analysis of prospective cohort studies
Authors: Hosseini Fatemeh , Jayedi Ahmad , Khan Tauseef Ahmad , Shab-Bidar Sakineh 
Published: February 2022

AbstractWe did this study to clarify the association between carbohydrate intake and the risk of type 2 diabetes (T2D) and potential effect modification by geographical location. PubMed, Scopus and Web of Science were searched to find prospective cohort studies of dietary carbohydrate intake and T2D risk. A random-effects dose–response meta-analysis was performed to calculate the summary hazard ratios (HRs) and 95%CIs. The quality of cohort studies and the certainty of evidence was rated using the Newcastle–Ottawa Scale and GRADE tool, respectively. Eighteen prospective cohort studies with 29,229 cases among 607,882 participants were included. Thirteen studies were rated to have high quality, and five as moderate quality. The HR for the highest compared with the lowest category of carbohydrate intake was 1.02 (95%CI: 0.91, 1.15; I2 = 67%, GRADE = low certainty). The HRs were 0.93 (95%CI: 0.82, 1.05; I2 = 58%, n = 7) and 1.26 (95%CI: 1.11, 1.44; I2 = 6%, n = 6) in Western and Asian countries, respectively. Dose–response analysis indicated a J shaped association, with the lowest risk at 50% carbohydrate intake (HR50%: 0.95, 95%CI: 0.90, 0.99) and with risk increasing significantly at 70% carbohydrate intake (HR70%: 1.18, 95%CI: 1.03, 1.35). There was no association between low carbohydrate diet score and the risk of T2D (HR: 1.14, 95%CI: 0.89, 1.47; I2 = 90%, n = 5). Carbohydrate intake within the recommended 45–65% of calorie intake was not associated with an increased risk of T2D. Carbohydrate intake more than 70% calorie intake might be associated with a higher risk.
Strength criterion of rock mass considering the damage and effect of joint dip angle
Authors: Li Yugen , Zhang Huimei , Chen Min , Meng Xiangzhen , Shen Yanjun , Liu Hui , Lu Yani 
Published: February 2022

AbstractIt is highly significant to theoretically assess the effect, under load, of initial stress and structure on the mass damage of rock mass. In this reported study, first a multi-factor coupling damage constitutive model under the action of joint-load was established by fully considering the non-uniformity, anisotropy and initial structure of a rock mass based on the Weibull distribution and D-P criterion. The relationship between the damage evolution and joint angle in the rock mass was elaborated. Then, a jointed rock mass strength criterion was built in line with the D–P criterion and the limit state of rock mass failure by the method of multivariate function total differential as based on the constitutive model. The results showed that the established constitutive model was in good agreement with the test results, which accurately reflected the damage characteristics of jointed rock mass during the entire loading process. The initial damage value of the rock mass increased with increasing joint dip angles, and the damage evolution of the jointed rock mass could be divided into the initial, stable, accelerated and failure damage stages. Comparing the results of this approach with other methods it was found that the strength criterion better reflected the effects of minimum principal stress σ3, volume stress σm, shear stress J21/2 and joint dip angle β on rock mass strength than other existing strength criteria, which showed that the proposed method offered important guiding principles for the engineering practice.
Using absolutist word frequency from online searches to measure population mental health dynamics
Authors: Adam-Troian Jais , Bonetto Eric , Arciszewski Thomas 
Published: February 2022

AbstractThe assessment of population mental health relies on survey data from representative samples, which come with considerable costs. Drawing on research which established that absolutist words (e.g. never) are semantic markers for depression, we propose a new measure of population mental health based on the frequency of absolutist words in online search data (absolute thinking index; ATI). Our aims were to first validate the ATI, and to use it to model public mental health dynamics in France and the UK during the current COVID-19 pandemic. To do so, we extracted time series for a validated dictionary of 19 absolutist words, from which the ATI was computed (weekly averages, 2019–2020,n = 208) using Google Trends. We then tested the relationship between ATI and longitudinal survey data of population mental health in the UK (n = 36,520) and France (n = 32,000). After assessing the relationship between ATI and survey measures of depression and anxiety in both populations, and dynamic similarities between ATI and survey measures (France), we tested the ATI’s construct validity by showing how it was affected by the pandemic and how it can be predicted by COVID-19-related indicators. A final step consisted in replicating ATI’s construct validity tests in Japan, thereby providing evidence for the ATI’s cross-cultural generalizability. ATI was linked with survey depression scores in the UK,r = 0.68, 95%CI[0.34,0.86],β = 0.23, 95%CI[0.09,0.37] in France and displayed similar trends. We finally assessed the pandemic’s impact on ATI using Bayesian structural time-series models. These revealed that the pandemic increased ATI by 3.2%, 95%CI[2.1,4.2] in France and 3.7%, 95%CI[2.9,4.4] in the UK. Mixed-effects models showed that ATI was related to COVID-19 new deaths in both countriesβ = 0.14, 95%CI[0.14,0.21]. These patterns were replicated in Japan, with a pandemic impact of 4.9%, 95%CI[3.1,6.7] and an influence of COVID-19 death ofβ = 0.90, 95%CI[0.36,1.44]. Our results demonstrate the validity of the ATI as a measure of population mental health (depression) in France, the UK and to some extent in Japan. We propose that researchers use it as cost-effective public mental health “thermometer” for applied and research purposes.
Dietary carbohydrate intake is associated with the subgingival plaque oral microbiome abundance and diversity in a cohort of postmenopausal women
Authors: Millen Amy E. , Dahhan Runda , Freudenheim Jo L. , Hovey Kathleen M. , Li Lu , McSkimming Daniel I. , Andrews Chris A. , Buck Michael J. , LaMonte Michael J. , Kirkwood Keith L. , Sun Yijun , Murugaiyan Vijaya , Tsompana Maria , Wactawski-Wende Jean 
Published: February 2022

AbstractLimited research exists on carbohydrate intake and oral microbiome diversity and composition assessed with next-generation sequencing. We aimed to better understand the association between habitual carbohydrate intake and the oral microbiome, as the oral microbiome has been associated with caries, periodontal disease, and systemic diseases. We investigated if total carbohydrates, starch, monosaccharides, disaccharides, fiber, or glycemic load (GL) were associated with the diversity and composition of oral bacteria in subgingival plaque samples of 1204 post-menopausal women. Carbohydrate intake and GL were assessed from a food frequency questionnaire, and adjusted for energy intake. The V3–V4 region of the 16S rRNA gene from subgingival plaque samples were sequenced to identify the relative abundance of microbiome compositional data expressed as operational taxonomic units (OTUs). The abundance of OTUs were centered log(2)-ratio transformed to account for the compositional data structure. Associations between carbohydrate/GL intake and microbiome alpha-diversity measures were examined using linear regression. PERMANOVA analyses were conducted to examine microbiome beta-diversity measures across quartiles of carbohydrate/GL intake. Associations between intake of carbohydrates and GL and the abundance of the 245 identified OTUs were examined by using linear regression. Total carbohydrates, GL, starch, lactose, and sucrose intake were inversely associated with alpha-diversity measures. Beta-diversity across quartiles of total carbohydrates, fiber, GL, sucrose, and galactose, were all statistically significant (p for PERMANOVA p < 0.05). Positive associations were observed between total carbohydrates, GL, sucrose and Streptococcus mutans; GL and both Sphingomonas HOT 006 and Scardovia wiggsiae; and sucrose and Streptococcus lactarius. A negative association was observed between lactose and Aggregatibacter segnis, and between sucrose and both TM7_[G-1] HOT 346 and Leptotrichia HOT 223. Intake of total carbohydrate, GL, and sucrose were inversely associated with subgingival bacteria alpha-diversity, the microbial beta-diversity varied by their intake, and they were associated with the relative abundance of specific OTUs. Higher intake of sucrose, or high GL foods, may influence poor oral health outcomes (and perhaps systemic health outcomes) in older women via their influence on the oral microbiome.