bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryo-EM Studies of Virus-Antibody Immune Complexes
Authors: Li Na , Li Zhiqiang , Fu Yan , Cao Sheng 
Published: January 2020

AbstractAntibodies play critical roles in neutralizing viral infections and are increasingly used as therapeutic drugs and diagnostic tools. Structural studies on virus-antibody immune complexes are important for better understanding the molecular mechanisms of antibody-mediated neutralization and also provide valuable information for structure-based vaccine design. Cryo-electron microscopy (cryo-EM) has recently matured as a powerful structural technique for studying bio-macromolecular complexes. When combined with X-ray crystallography, cryo-EM provides a routine approach for structurally characterizing the immune complexes formed between icosahedral viruses and their antibodies. In this review, recent advances in the structural understanding of virus-antibody interactions are outlined for whole virions with icosahedral T = pseudo 3 (picornaviruses) and T = 3 (flaviviruses) architectures, focusing on the dynamic nature of viral shells in different functional states. Glycoprotein complexes from pleomorphic enveloped viruses are also discussed as immune complex antigens. Improving our understanding of viral epitope structures using virus-based platforms would provide a fundamental road map for future vaccine development.
Graph-based data clustering via multiscale community detection
Authors: Liu Zijing , Barahona Mauricio 
Published: January 2020

AbstractWe present a graph-theoretical approach to data clustering, which combines the creation of a graph from the data with Markov Stability, a multiscale community detection framework. We show how the multiscale capabilities of the method allow the estimation of the number of clusters, as well as alleviating the sensitivity to the parameters in graph construction. We use both synthetic and benchmark real datasets to compare and evaluate several graph construction methods and clustering algorithms, and show that multiscale graph-based clustering achieves improved performance compared to popular clustering methods without the need to set externally the number of clusters.
Future developments in standardisation of cyber risk in the Internet of Things (IoT)
Authors: Radanliev Petar , De Roure David C. , Nurse Jason R. C. , Mantilla Montalvo Rafael , Cannady Stacy , Santos Omar , Maddox La’Treall , Burnap Peter , Maple Carsten 
Published: January 2020

AbstractIn this research article, we explore the use of a design process for adapting existing cyber risk assessment standards to allow the calculation of economic impact from IoT cyber risk. The paper presents a new model that includes a design process with new risk assessment vectors, specific for IoT cyber risk. To design new risk assessment vectors for IoT, the study applied a range of methodologies, including literature review, empirical study and comparative study, followed by theoretical analysis and grounded theory. An epistemological framework emerges from applying the constructivist grounded theory methodology to draw on knowledge from existing cyber risk frameworks, models and methodologies. This framework presents the current gaps in cyber risk standards and policies, and defines the design principles of future cyber risk impact assessment. The core contribution of the article therefore, being the presentation of a new model for impact assessment of IoT cyber risk.
Challenge in the new era: Translational medicine in gastrointestinal endoscopy and early cancer
Authors: Yu Yang , Yin Yan‐Hua , Min Li , Zhu Sheng‐Tao , Li Peng , Zhang Shu‐Tian 
Published: January 2020

AbstractTranslational medicine is a new medical model that has emerged over the past 20 years and is dedicated to bridging the gap between basic and clinical research. At the same time, the diagnosis and treatment of digestive diseases, especially gastrointestinal endoscopy, have been rapidly developed. The emergence of new techniques for gastrointestinal endoscopy has changed the therapeutic spectrum of some diseases and brought huge benefits to patients. Targeted therapy has positively affected the individualized and precise treatment of patients with advanced gastrointestinal cancer. The construction of a standardized biobank provides a strong guarantee for clinicians to conduct translational medical research. Translational medicine has brought good development opportunities, but it also faces challenges. The training of translational medicine researchers and the transformation of educational models require sufficient attention for further development.
Diagnosis and treatment ofHelicobacter pyloriinfections in children and elderly populations
Authors: Peng Chao , Hu Yi , Ge Zhong‐Ming , Zou Quan‐Ming , Lyu Nong‐Hua 
Published: January 2020

AbstractHelicobacter pylori(H. pylori) infection is associated with various gastric and extra‐gastric diseases. Importantly, this infection is the strongest known risk factor for gastric cancer (GC).H. pylorieradication can effectively preventH. pyloriinfection‐associated diseases inH. pylori‐positive patients, including children and elderly subjects. However, a limited selection of antibiotics, a higher reinfection rate, and certain spontaneous clearance rates, to some extent, restrict the choice ofH. pyloritreatments in pediatrics. In addition, it is imperative to perform an accurate diagnosis ofH. pyloriinfection in children by determining the presence of theH. pyloriinfection and the underlying cause of symptoms. In elderly patients, poor tolerance to drugs and higher sensitivity to adverse effects are major concerns duringH. pyloritherapy. Recent studies have demonstrated thatH. pylorieradication could significantly lower the GC risk in the elderly population. The benefit and risk ofH. pylorieradication in elderly patients should be comprehensively considered and balanced. If available, susceptibility‐based tailored therapies may be preferable in eradicatingH. pylori. In addition, to increase the eradication rate and reduce adverse effects, new therapeutic strategies (e.g., probiotic supplementation, berberine supplementation, dual therapy) forH. pyloriinfection are being extensively investigated. The impact ofH. pylorieradication with antibiotics on the microbiota in children has been explored, but further high‐quality studies are crucial to delineate the extent ofH. pylorieradication affecting the microbial community in children. In this review, we summarize the current understanding ofH. pyloridiagnosis and treatment in children and the elderly population and aim to provide insights into the efficient management and treatment implementation in these populations.
Long non‐coding RNAs as novel diagnostic and therapeutic targets in kidney disease
Authors: Zhou Qin , Chen Wei , Yu Xue‐Qing 
Published: January 2020

AbstractLong non‐coding RNAs (lncRNAs) have critical roles in the development of many diseases including kidney disease. An increasing number of studies have shown that lncRNAs are involved in kidney development and that their dysregulation can result in distinct disease processes, including acute kidney injury (AKI), chronic kidney disease (CKD), and renal cell carcinoma (RCC). Understanding the roles of lncRNAs in kidney disease may provide new diagnostic and therapeutic opportunities in the clinic. This review provides an overview of lncRNA characteristics, biological function and discusses specific studies that provide insight into the function and potential application of lncRNAs in kidney disease treatment.
Underweight, body image, and weight loss measures among adolescents in Saudi Arabia
Authors: Hijji Talal M. , Saleheen Hassan , AlBuhairan Fadia S. 
Published: January 2020

Background and Objective:
Adolescence is considered to be a pivotal point in which optimum nutrition and eating habits are developed. Although tackling the obesity epidemic has been much discussed, addressing the issue of underweight and body image is often neglected. This study was carried out to get a better understanding of underweight status among adolescents in Saudi Arabia, and exploring self-perceptions of body image and weight loss measures among underweight adolescents.

Methods:
Data from Jeeluna®, a national cross-sectional school-based survey were utilized. Jeeluna® assessed the health status and health-risk behaviors of adolescents in school through data obtained by a self-administered questionnaire, anthropologic measurements, and laboratory investigations.

Results:
A total of 12,463 adolescents participated. Eighteen percent of adolescent males and 12.4% of females were found to be underweight, representing 14.9% of adolescents collectively. Forty-five percent of underweight participants were happy with their weight. Underweight females between the age group of 10 and 14 years were the most likely to believe that they still need to lose weight (16.0%) followed by females aged 15–19 years (9.7%). Underweight females aged 10–14 years were also the group most likely to engage in purging (1.6%). Stepwise logistic regression found that the strongest association with being underweight was with having a lower household income (OR 2.0, CI 1.5–2.7) and having more than 5 siblings (OR 1.8, CI 1.5–2.3).

Conclusion:
Underweight status is prevalent among adolescents in Saudi Arabia and deserves more attention as a public health issue. Distorted body image and disordered eating behaviors exist, necessitating further investigation of underlying causes.
Interaction of recommended levels of physical activity and protein intake is associated with greater physical function and lower fat mass in older women: Kuopio Osteoporosis Risk Factor- (OSTPRE) and Fracture-Prevention Study
Authors: Sjöblom Samu , Sirola Joonas , Rikkonen Toni , Erkkilä Arja T. , Kröger Heikki , Qazi Sarang L. , Isanejad Masoud 
Published: January 2020

AbstractThe aim of the study was to investigate whether the interaction of physical activity (PA) and protein intake is associated with physical function (PF). The women from the Osteoporosis Risk Factor and Fracture Prevention Study (n 610) completed a questionnaire on lifestyle factors and PA and underwent PF and body composition measurements at baseline (BL) and over 3 years of follow-up (3y-FU). PA was categorised according to WHO cut-off PA = 0, 0 < PA < 2·5 and PA ≥ 2·5 h/week. Protein intake was calculated from the 3-d food record at baseline and categorised according to the Nordic Nutrition Recommendations <1·1 and ≥1·1 g/kg body weight (BW). The results showed in univariate ANOVA at the baseline and at the 3-year follow-up, women with high PA ≥ 2·5 h/week and protein intake ≥ 1·1 g/kg BW had higher grip strength adjusted for BMI, higher mean number of chair rises, faster mean walking speed, higher modified mean short physical performance battery score and lower mean fat mass compared with other interaction groups. High PA and protein intake were associated with lower BMI despite significantly higher energy intake. In conclusion, higher PA and protein intake interaction was associated with greater PF and lower fat mass, but the association with relative skeletal muscle index and muscle mass was inconclusive. The present study gives noteworthy information for preventing sarcopenia.
Evolution of the Charge Structure and Lightning Discharge Characteristics of a Qinghai‐Tibet Plateau Thunderstorm Dominated by Negative Cloud‐to‐Ground Flashes
Authors: Li Yajun , Zhang Guangshu , Zhang Yijun 
Published: January 2020

AbstractThe correlation between the charge structure evolution and lightning type and frequency for a multicell thunderstorm dominated by negative cloud‐to‐ground (CG) flash on the Qinghai‐Tibet Plateau was analyzed using observations from a three‐dimensional lightning very high frequency radiation source location system. The analysis results showed the following. (1) In the initial developing stage of the thunderstorm, each cell developed independently and presented an inverted dipole charge structure. As the thunderstorm developed into its mature stage, multiple cells merged, and the charge structure changed to a tripole structure. In the dissipation stage of each thunderstorm region, the charge structure reverted to an inverted dipole or a normal dipole. (2) When the extent of the charge region expanded, the upper and lower charge regions became uneven and asymmetric. (3) In the inverted dipole charge structure, negative CG flashes accounted for 77.2% of the total number of lightning flashes, whereas negative intracloud flashes accounted for only 22.8%. In the tripole charge structure, negative CG flashes, positive intracloud flashes, and negative intracloud flashes accounted for 62%, 21%, and 16%, respectively, of all lightning flashes. These results indicate that the middle negative charge region was the strongest layer of the thunderstorm, while the upper positive charge region was slightly stronger, and the lower positive charge region was the weakest. These findings also indicate that the relative intensity of the charge layers directly determined the lightning quantity and frequency.
Simulations of Winter Arctic Clouds and Associated Radiation Fluxes Using Different Cloud Microphysics Schemes in the Polar WRF: Comparisons With CloudSat, CALIPSO, and CERES
Authors: Cho Heeje , Jun Sang‐Yoon , Ho Chang‐Hoi , McFarquhar Greg 
Published: January 2020

Key Points

Winter Arctic clouds simulated by the polar version of the Weather Research and Forecasting model are compared with satellite retrievals
The cloud amount and cloud top height of model simulations agree well with those of satellite retrievals
The downward longwave radiation at the surface shows realistic temporal variations, but is sensitive to the cloud microphysics scheme choice
N-glycosylated SGK196 suppresses the metastasis of basal-like breast cancer cells
Authors: Xu Ci , Zhang Meichao , Bian Lei , Li Yanyan , Yao Yuan , Li Dong 
Published: January 2020

AbstractSGK196 is a protein O-mannose kinase involved in an indispensable phosphorylation step during laminin-binding glycan synthesis on alpha-dystroglycan (α-DG). However, the function of SGK196 in cancer diseases remains elusive. In the current study, we demonstrated that SGK196 is primarily modified by N-glycosylation in breast cancer (BC) cells. Furthermore, gain and loss-of-function studies showed that N-glycosylated SGK196 suppresses cell migration, invasion, and metastasis in BC, particularly in the basal-like breast cancer (BLBC) type. In addition, we found that SGK196 N-glycosylation performs the regulatory function through the PI3K/AKT/GSK3β signaling pathway. Collectively, our results show that N-glycosylated SGK196 plays suppression roles in BLBC metastases, therefore providing new insights into SGK196 function in BC.
Long-term outcomes of IMiD-based trials in patients with immunoglobulin light-chain amyloidosis: a pooled analysis
Authors: Warsame Rahma , LaPlant Betsy , Kumar Shaji K. , Laumann Kristina , Perez Burbano Gabriela , Buadi Francis K. , Gertz Morie A. , Kyle Robert A. , Lacy Martha Q. , Dingli David , Leung Nelson , Hayman Suzanne R. , Kapoor Prashant , Hwa Yi L. , Fonder Amie , Hobbs Miriam , Gonsalves Wilson I. , Kourelis Taxiarchis , Lust John , Russell Stephen J. , Zeldenrust Steven , Lin Yi , Muchtar Eli , Go Ronald S. , Vincent Rajkumar S. , Dispenzieri Angela 
Published: January 2020

AbstractRarity of light-chain amyloidosis (AL) makes randomized studies challenging. We pooled three phase II studies of immunomodulatory drugs (IMiDs) to update survival, toxicity, and assess new response/progression criteria. Studies included were lenalidomide-dexamethasone (Len-Dex) (n = 37; years: 2004–2006), cyclophosphamide-Len-Dex (n = 35; years: 2007–2008), and pomalidomide-Dex (n = 29; years: 2008–2010) trial. Primary endpoint was hematologic response. Overall survival (OS) was calculated from registration to death and progression-free survival (PFS) was calculated from registration to progression or death. Hematologic, cardiac, and renal response/progression was assessed using the modern criteria. Analysis included 101 patients, with a median age of 65 years, 61% male, 37 newly diagnosed (ND), and 64 relapsed/refractory (RR). Median follow-up was 101 months (range 17–150) and 78% of patients died. OS and PFS for pooled cohort were 31 and 15 months, respectively. Forty-eight patients achieved a hematologic response; for ND, 10 patients (28%) achieved ≥VGPR (very good partial response) and 8 (14%) among the RR. Only cardiac stage was prognostic for OS. Common grade ≥3 toxicities were hematologic, fatigue, and rash, and were similar among studies. Hematologic and renal responses occurred more frequently and rapidly using modern response criteria; cardiac response was less frequent but occurred quickly. IMiDs can result in long progression-free intervals/survival with tolerable toxicities. The new response/progression criteria were rapid and allows for tailoring therapy.
Prox1-positive cells monitor and sustain the murine intestinal epithelial cholinergic niche
Authors: Middelhoff Moritz , Nienhüser Henrik , Valenti Giovanni , Maurer H. Carlo , Hayakawa Yoku , Takahashi Ryota , Kim Woosook , Jiang Zhengyu , Malagola Ermanno , Cuti Krystle , Tailor Yagnesh , Zamechek Leah B. , Renz Bernhard W. , Quante Michael , Yan Kelley S. , Wang Timothy C. 
Published: January 2020

AbstractThe enteric neurotransmitter acetylcholine governs important intestinal epithelial secretory and immune functions through its actions on epithelial muscarinic Gq-coupled receptors such as M3R. Its role in the regulation of intestinal stem cell function and differentiation, however, has not been clarified. Here, we find that nonselective muscarinic receptor antagonism in mice as well as epithelial-specific ablation of M3R induces a selective expansion of DCLK1-positive tuft cells, suggesting a model of feedback inhibition. Cholinergic blockade reduces Lgr5-positive intestinal stem cell tracing and cell number. In contrast, Prox1-positive endocrine cells appear as primary sensors of cholinergic blockade inducing the expansion of tuft cells, which adopt an enteroendocrine phenotype and contribute to increased mucosal levels of acetylcholine. This compensatory mechanism is lost with acute irradiation injury, resulting in a paucity of tuft cells and acetylcholine production. Thus, enteroendocrine tuft cells appear essential to maintain epithelial homeostasis following modifications of the cholinergic intestinal niche.
Ultra-thin van der Waals crystals as semiconductor quantum wells
Authors: Zultak Johanna , Magorrian Samuel J. , Koperski Maciej , Garner Alistair , Hamer Matthew J. , Tóvári Endre , Novoselov Kostya S. , Zhukov Alexander A. , Zou Yichao , Wilson Neil R. , Haigh Sarah J. , Kretinin Andrey V. , Fal’ko Vladimir I. , Gorbachev Roman 
Published: January 2020

AbstractControl over the quantization of electrons in quantum wells is at the heart of the functioning of modern advanced electronics; high electron mobility transistors, semiconductor and Capasso terahertz lasers, and many others. However, this avenue has not been explored in the case of 2D materials. Here we apply this concept to van der Waals heterostructures using the thickness of exfoliated crystals to control the quantum well dimensions in few-layer semiconductor InSe. This approach realizes precise control over the energy of the subbands and their uniformity guarantees extremely high quality electronic transport in these systems. Using tunnelling and light emitting devices, we reveal the full subband structure by studying resonance features in the tunnelling current, photoabsorption and light emission spectra. In the future, these systems could enable development of elementary blocks for atomically thin infrared and THz light sources based on intersubband optical transitions in few-layer van der Waals materials.
Clinically accurate diagnosis of Alzheimer’s disease via multiplexed sensing of core biomarkers in human plasma
Authors: Kim Kayoung , Kim Min-Ji , Kim Da Won , Kim Su Yeong , Park Steve , Park Chan Beum 
Published: January 2020

AbstractAlzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, affecting one in ten people aged over 65 years. Despite the severity of the disease, early diagnosis of AD is still challenging due to the low accuracy or high cost of neuropsychological tests and neuroimaging. Here we report clinically accurate and ultrasensitive detection of multiple AD core biomarkers (t-tau, p-tau181, Aβ42, and Aβ40) in human plasma using densely aligned carbon nanotubes (CNTs). The closely packed and unidirectionally aligned CNT sensor array exhibits high precision, sensitivity, and accuracy, evidenced by a low coefficient of variation (<6%), a femtomolar-level limit of detection, and a high degree of recovery (>93.0%). By measuring the levels of t-tau/Aβ42, p-tau181/Aβ42, and Aβ42/Aβ40 in clinical blood samples, the sensor array successfully discriminates the clinically diagnosed AD patients from healthy controls with an average sensitivity of 90.0%, a selectivity of 90.0%, and an average accuracy of 88.6%.
Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation
Authors: Mooser Clémence , Symeonidou Ioanna-Eleni , Leimbacher Pia-Amata , Ribeiro Alison , Shorrocks Ann-Marie K. , Jungmichel Stephanie , Larsen Sara C. , Knechtle Katja , Jasrotia Arti , Zurbriggen Diana , Jeanrenaud Alain , Leikauf Colin , Fink Daniel , Nielsen Michael L. , Blackford Andrew N. , Stucki Manuel 
Published: January 2020

AbstractInduction of DNA double-strand breaks (DSBs) in ribosomal DNA (rDNA) repeats is associated with ATM-dependent repression of ribosomal RNA synthesis and large-scale reorganization of nucleolar architecture, but the signaling events that regulate these responses are largely elusive. Here we show that the nucleolar response to rDNA breaks is dependent on both ATM and ATR activity. We further demonstrate that ATM- and NBS1-dependent recruitment of TOPBP1 in the nucleoli is required for inhibition of ribosomal RNA synthesis and nucleolar segregation in response to rDNA breaks. Mechanistically, TOPBP1 recruitment is mediated by phosphorylation-dependent interactions between three of its BRCT domains and conserved phosphorylated Ser/Thr residues at the C-terminus of the nucleolar phosphoprotein Treacle. Our data thus reveal an important cooperation between TOPBP1 and Treacle in the signaling cascade that triggers transcriptional inhibition and nucleolar segregation in response to rDNA breaks.