bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal exposure to O3 and NO2 may increase the risk of newborn congenital hypothyroidism: a national data-based analysis in China
Authors: Qi Cuifang , Shang Li , Yang Wenfang , Huang Liyan , Yang Liren , Xin Juan , Wang Shanshan , Yue Jie , Zeng Lingxia , Chung Mei Chun
Published: March 2021

Maternal exposure to air pollution during pregnancy is associated with adverse outcomes in the offspring, but limited studies focused on the impacts of gaseous air pollution on newborn congenital hypothyroidism (CH). Therefore, a national data-based analysis was conducted to explore the association between maternal exposure to gaseous air pollution and the incidence of CH in China. Annual average exposure levels of SO2, NO2, CO, and O3 from January 1, 2014, to December 30, 2014, were acquired from the Chinese Air Quality Online Monitoring and Analysis Platform. The annual incidence of newborn CH from October 1, 2014, to September 30, 2015, was collected from the Chinese Maternal and Child Health Surveillance Network. Temperature and toxic metal in wastewater in 2014 were also collected as covariates. Maternal exposure to O3 and NO2 in 1 μg/m3 level increment was positively associated with newborn CH, with an OR of 1.055 (95% CI 1.011, 1.102) and 1.097 (95% CI 1.019, 1.182) after adjusting for covariates completely. Compared with the lowest level of O3, maternal exposure to the 4th quartile of O3 was positively associated with newborn CH (OR 1.393, 95% CI 1.081, 1.794) after adjusting for covariates completely. And the 3rd and 4th quartiles of NO2 were associated positively with CH (OR 1.576, 95% CI 1.025, 2.424, and OR 1.553, 95% CI 0.999, 2.414, respectively) compared with the lowest level of NO2. By fitting the ROC curve, 93.688 μg/m3 in O3 might be used as cutoff to predict the incidence of newborn CH in China.
Managing performance and winning trust: how World Bank staff shape recipient performance
Authors: Heinzel Mirko , Liese Andrea
Published: March 2021

World Bank evaluations show that recipient performance varies substantially between different projects. Extant research has focused on country-level variables when explaining these variations. This article goes beyond country-level explanations and highlights the role of World Bank staff. We extend established arguments in the literature on compliance with the demands of International Organizations (IOs) and hypothesize that IO staff can shape recipient performance in three ways. First, recipient performance may be influenced by the quality of IO staff monitoring and supervision. Second, the leniency and stringency with which IO staff apply the aid agreement could improve recipient performance. Third, recipient performance may depend on whether IO staff can identify and mobilize supportive interlocutors through their networks in the recipient country. We test these arguments by linking a novel database on the tenure of World Bank task team leaders to projects evaluated between 1986 and 2020. The findings are consistent with the expectation that World Bank staff play an important role, but only in investment projects. There is substantial evidence that World Bank staff supervisory ability and country experience are linked to recipient performance in those projects. Less consistent evidence indicates that leniency could matter. These findings imply that World Bank staff play an important role in facilitating implementation of investment projects.
Improving machinability of additively manufactured components with selectively weakened material
Authors: Maucher Clemens , Teich Heiko , Möhring Hans-Christian
Published: March 2021

Part design and the possibilities of production are disrupted by the increased usage of additive manufacturing (AM). Featuring excellent creative freedom due to the layer-by-layer buildup of components, AM leads to profound changes in future part design and enables previously impossible geometries. Laser powder bed fusion (LPBF) technology already allows to manufacture small quantities of parts with high productivity and material efficiency. Due to the specific process characteristics, the resulting surface finish of these parts is insufficient for a wide range of applications, and post-processing is usually unavoidable. Specifically for functional surfaces, this post-processing is often done by machining processes, which can pose challenges for intricate and complex AM parts due to excessive machining forces. In the present paper, the influence and the possibilities of the LPBF process parameters on the subtractive post-processing are shown. A novel weakened structure is developed to selectively reduce the strength of the material and improve the cutting conditions. Chip formation, cutting forces and vibrations during drilling as well as cutting forces during an orthogonal cut are examined. To quantify the differences, a comparison of the machinability between bulk material, standard support structures and the weakened structure is carried out.
Local Regularity for the Harmonic Map and Yang–Mills Heat Flows
Authors: Afuni Ahmad
Published: March 2021

We establish new local regularity results for the harmonic map and Yang–Mills heat flows on Riemannian manifolds of dimension greater than 2 and 4, respectively, obtaining criteria for the smooth local extensibility of these flows. As a corollary, we obtain new characterisations of singularity formation and use this to obtain a local estimate on the Hausdorff measure of the singular sets of these flows at the first singular time. Finally, we show that smooth blow-ups at rapidly forming singularities of these flows are necessarily nontrivial and admit a positive lower bound on their heat ball energies. These results crucially depend on some local monotonicity formulæ for these flows recently established by Ecker (Calc Var Partial Differ Equ 23(1):67–81, 2005) and the Afuni (Calc Var 555(1):1–14, 2016; Adv Calc Var 12(2):135–156, 2019).
Development and Implementation of Situational Judgment Tests as an Evaluation Method for Training Oncology Physicians: Application in the KOKON-KTO Training
Authors: Rogge Alizé A. , Helmer Stefanie M. , Kiessling Claudia , Witt Claudia M.
Published: March 2021

Situational judgment tests (SJTs) are often used in aptitude testing and present practice-specific challenges. Their implementation into online training programs provides the opportunity to assess learning progress and improve training quality. In this study, text-based SJTs for oncology physicians were developed, validated, and implemented into the KOKON-KTO training which uses a blended learning training format to teach oncology physicians how to consult cancer patients on complementary and integrative medicine (CIM). The SJT was implemented to measure the e-learning results. In the development and validation phase, a total of 15 SJTs (each SJT including 1 best choice answer based on training content and 4 distractors; 9 SJTs for oncologists and 6 SJTs for oncology gynecologists only) were developed by an interprofessional team (n=5) using real-case vignettes and applying an in-depth review process. Best answers were validated by experts (oncologists and oncology gynecologists) with experience in advising cancer patients on CIM. In the implementation and evaluation phase, SJTs were answered by KOKON-KTO training participants (n=19) pre- and post e-learning. Results were analyzed using descriptive measurements, item difficulties, and Cohen’s d for effect size pre- and post-training. The experts (n=12, 49.8% gynecologists) agreed with best choice answers (69.4% for oncology gynecology; 81.5% for oncology) in 12 out of 15 SJTs. Comparing pre- and post-training scores, KOKON-KTO training participants were able to improve knowledge substantially (effect sizes for oncologists d=1.7; oncology gynecologists d= .71). Future studies need to increase the number of experts and SJTs in order to apply further psychometric measurements. As part of the KOKON-KTO study, this project is registered as DRKS00012704 on the “German Clinical Trials Register” (Date of registration: 28.08.2017).
A power-quality monitoring and assessment system for high-speed railways based on train-network-data center integration
Authors: Zhu Jun , Hu Haitao , He Zhengyou , Guo Xiaomin , Pan Weiguo
Published: March 2021

In recent years, with the rapid development of high-speed railways (HSRs), power interruptions or disturbances in traction power supply systems have become increasingly dangerous. However, it is often impossible to detect these faults immediately through single-point monitoring or collecting data after accidents. To coordinate the power quality data of both traction power supply systems (TPSSs) and high-speed trains (HSTs), a monitoring and assessing system is proposed to access the power quality issues on HSRs. By integrating train monitoring, traction substation monitoring and data center, this monitoring system not only realizes the real-time monitoring of operational behaviors for both TPSSs and HSTs, but also conducts a comprehensive assessment of operational quality for train-network systems. Based on a large number of monitoring data, the field measurements show that this real-time monitoring system is effective for monitoring and evaluating a traction-network system.
Laboratory results of foam application testing for longwall shield dust control in a simulated environment
Authors: Reed W. R. , Shahan M. R. , Zheng Y. , Mazzella A.
Published: March 2021

There were 37 longwall faces operating in mines in the United States in 2019. The average panel width for these longwalls was approximately 368.5 m (1209 ft). This translates to a range of approximately 170–240 shields per longwall, depending upon the width of shield. The movement of longwall shields is a significant contributor to respirable dust overexposures to longwall operators. Foam is expected to have the potential to reduce this shield dust generation. The foam is applied to the area on the roof between the coal face and the shield tip after the shearer passes. In this study, the longwall shield dust simulator was used to test three foam agents for their ability to control dust from longwall shield movements. Results showed that at low-velocity ventilation (≈ 3.0 m/s (600 fpm)) all foam agents were able to produce dust reduction levels of at least 45%. At high-velocity ventilation (≈ 5.1 m/s (1000 fpm)), the reductions were lower and more variable, ranging from being undeterminable for one foam agent to having 46%–63% reductions for the other two foam agents, with one instance of an increase in dust concentration. Overall, the use of foam agents can provide longwall shield dust control. Important factors are roof coverage and the ability of foam to remain on the roof for extended time periods.
Presenting new approach for optimal placement of nuclear power plant connected to the grid after the trip
Authors: Kiomarsi Farshid , Shojaei Ali Asghar , Soltani Sepehr , Lotfi Hossein
Published: March 2021

This study presents a combination of optimal placement and power system development with the aim of supplying electricity for Nuclear Power Plant after the trip of power plant. Power supply to the internal loads of power plant by the off-site power system is one of the main fields of research in achieving the safety Nuclear Power Plant. One of the main purposes in this article is to introduce a suitable and safe place for the construction and connection of a Nuclear Power Plant to the power system. These locations are identified by the power plants on-site loads and the average of the lowest number of relay protection after the Nuclear Power Plant trip, based on electricity considerations. Along with the optimal placement in this paper, the power system development, including the generation and transmission development in order to provide electricity with higher reliability to the Nuclear Power Plant after the trip is also presented. Monte Carlo and Latin Hypercube Sampling probabilistic methods are proposed for locating the site of a Nuclear Power Plant and algorithms of Genetic and Particle Swarm Optimization for locating and developing power generation and transmission systems. The simulation results are implemented on the IEEE RTS 24-bus system, and finally suitable locations for the construction of the Nuclear Power Plant and the generation and transmission development with the aim of feeding the power plant from the off-site power system and sufficient assurance that the reactor core does not melt after the trip, are determined.
DeeReCT-APA: Prediction of Alternative Polyadenylation Site Usage Through Deep Learning
Authors: Li Zhongxiao , Li Yisheng , Zhang Bin , Li Yu , Long Yongkang , Zhou Juexiao , Zou Xudong , Zhang Min , Hu Yuhui , Chen Wei , Gao Xin
Published: March 2021

Alternative polyadenylation (APA) is a crucial step in post-transcriptional regulation. Previous bioinformatic studies have mainly focused on the recognition of polyadenylation sites (PASs) in a given genomic sequence, which is a binary classification problem. Recently, computational methods for predicting the usage level of alternative PASs in the same gene have been proposed. However, all of them cast the problem as a non-quantitative pairwise comparison task and do not take the competition among multiple PASs into account. To address this, here we propose a deep learning architecture, Deep Regulatory Code and Tools for Alternative Polyadenylation (DeeReCT-APA), to quantitatively predict the usage of all alternative PASs of a given gene. To accommodate different genes with potentially different numbers of PASs, DeeReCT-APA treats the problem as a regression task with a variable-length target. Based on a convolutional neural network-long short-term memory (CNN-LSTM) architecture, DeeReCT-APA extracts sequence features with CNN layers, uses bidirectional LSTM to explicitly model the interactions among competing PASs, and outputs percentage scores representing the usage levels of all PASs of a gene. In addition to the fact that only our method can quantitatively predict the usage of all the PASs within a gene, we show that our method consistently outperforms other existing methods on three different tasks for which they are trained: pairwise comparison task, highest usage prediction task, and ranking task. Finally, we demonstrate that our method can be used to predict the effect of genetic variations on APA patterns and sheds light on future mechanistic understanding in APA regulation. Our code and data are available at https://github.com/lzx325/DeeReCT-APA-repo.
CharPlant: A De Novo Open Chromatin Region Prediction Tool for Plant Genomes
Authors: Shen Yin , Chen Ling-Ling , Gao Junxiang
Published: March 2021

Chromatin accessibility is a highly informative structural feature for understanding gene transcription regulation, because it indicates the degree to which nuclear macromolecules such as proteins and RNAs can access chromosomal DNA. Studies have shown that chromatin accessibility is highly dynamic during stress response, stimulus response, and developmental transition. Moreover, physical access to chromosomal DNA in eukaryotes is highly cell-specific. Therefore, current technologies such as DNase-seq, ATAC-seq, and FAIRE-seq reveal only a portion of the open chromatin regions (OCRs) present in a given species. Thus, the genome-wide distribution of OCRs remains unknown. In this study, we developed a bioinformatics tool called CharPlant for the de novo prediction of OCRs in plant genomes. To develop this tool, we constructed a three-layer convolutional neural network (CNN) and subsequently trained the CNN using DNase-seq and ATAC-seq datasets of four plant species. The model simultaneously learns the sequence motifs and regulatory logics, which are jointly used to determine DNA accessibility. All of these steps are integrated into CharPlant, which can be run using a simple command line. The results of data analysis using CharPlant in this study demonstrate its prediction power and computational efficiency. To our knowledge, CharPlant is the first de novo prediction tool that can identify potential OCRs in the whole genome. The source code of CharPlant and supporting files are freely available from https://github.com/Yin-Shen/CharPlant.
The Comparative Politics of Immigration
Authors: Ellermann Antje
Published: March 2021

Many governments face similar pressures surrounding the hotly debated topic of immigration. Yet, the disparate ways in which policy makers respond is striking. The Comparative Politics of Immigration explains why democratic governments adopt the immigration policies they do. Through an in-depth study of immigration politics in Germany, Canada, Switzerland, and the United States, Antje Ellermann examines the development of immigration policy from the postwar era to the present. The book presents a new theory of immigration policymaking grounded in the political insulation of policy makers. Three types of insulation shape the translation of immigration preference into policy: popular insulation from demands of the unorganized public, interest group insulation from the claims of organized lobbies, and diplomatic insulation from the lobbying of immigrant-sending states. Addressing the nuances in immigration reforms, Ellermann analyzes both institutional factors and policy actors' strategic decisions to account for cross-national and temporal variation.
Postextraction infection and antibiotic prescribing among veterans receiving dental extractions
Authors: Caniff Kaylee E. , Young Lisa R. , Truong Shawna , Gibson Gretchen , Jurasic M. Marianne , Poggensee Linda , Fitzpatrick Margaret A. , Evans Charlesnika T. , Suda Katie J.
Published: March 2021

Objective:

To characterize postextraction antibiotic prescribing patterns, predictors for antibiotic prescribing and the incidence of and risk factors for postextraction oral infection.

Design:

Retrospective analysis of a random sample of veterans who received tooth extractions from January 1, 2017 through December 31, 2017.

Setting:

VA dental clinics.

Patients:

Overall, 69,610 patients met inclusion criteria, of whom 404 were randomly selected for inclusion. Adjunctive antibiotics were prescribed to 154 patients (38.1%).

Intervention:

Patients who received or did not receive an antibiotic were compared for the occurrence of postextraction infection as documented in the electronic health record. Multivariable logistic regression was performed to identify factors associated with antibiotic receipt.

Results:

There was no difference in the frequency of postextraction oral infection identified among patients who did and did not receive antibiotics (4.5% vs 3.2%; P = .59). Risk factors for postextraction infection could not be identified due to the low frequency of this outcome. Patients who received antibiotics were more likely to have a greater number of teeth extracted (aOR, 1.10; 95% CI, 1.03–1.18), documentation of acute infection at time of extraction (aOR, 3.02; 95% CI, 1.57–5.82), molar extraction (aOR, 1.78; 95% CI, 1.10–2.86) and extraction performed by an oral maxillofacial surgeon (aOR, 2.29; 95% CI, 1.44–3.58) or specialty dentist (aOR, 5.77; 95% CI, 2.05–16.19).

Conclusion:

Infectious complications occurred at a low incidence among veterans undergoing tooth extraction who did and did not receive postextraction antibiotics. These results suggest that antibiotics have a limited role in preventing postprocedural infection; however, future studies are necessary to more clearly define the role of antibiotics for this indication.
Is a reduction in viability enough to determine biofilm susceptibility to a biocide?
Authors: Ledwoch Katarzyna , Magoga Maddalena , Williams Dulcie , Fabbri Stefania , Walsh James , Maillard Jean-Yves
Published: March 2021

Objective:

The abundance and prevalence of dry-surface biofilms (DSBs) in hospitals constitute an emerging problem, yet studies rarely report the cleaning and disinfection efficacy against DSBs. Here, the combined impact of treatments on viability, transferability, and recovery of bacteria from DSBs has been investigated for the first time.

Methods:

Staphylococcus aureus DSBs were produced in alternating 48-hour wet–dry cycles for 12 days on AISI 430 stainless steel discs. The efficacy of 11 commercially available disinfectants, 4 detergents, and 2 contactless interventions were tested using a modified standardized product test. Reduction in viability, direct transferability, cross transmission (via glove intermediate), and DSB recovery after treatment were measured.

Results:

Of 11 disinfectants, 9 were effective in killing and removing bacteria from S. aureus DSBs with >4 log10 reduction. Only 2 disinfectants, sodium dichloroisocyanurate 1,000 ppm and peracetic acid 3,500 ppm, were able to lower both direct and cross transmission of bacteria (<2 compression contacts positive for bacterial growth). Of 11 disinfectants, 8 could not prevent DSB recovery for >2 days. Treatments not involving mechanical action (vaporized hydrogen peroxide and cold atmospheric plasma) were ineffective, producing <1 log10 reduction in viability, DSB regrowth within 1 day, and 100% transferability of DSB after treatment.

Conclusions:

Reduction in bacterial viability alone does not determine product performance against biofilm and might give a false sense of security to consumers, manufacturers and regulators. The ability to prevent bacterial transfer and biofilm recovery after treatment requires a better understanding of the effectiveness of biocidal products.
Future glacial lakes in High Mountain Asia: an inventory and assessment of hazard potential from surrounding slopes
Authors: Furian Wilhelm , Loibl David , Schneider Christoph
Published: March 2021

Bedrock overdeepenings exposed by continued glacial retreat can store precipitation and meltwater, potentially leading to the formation of new proglacial lakes. These lakes may pose threats of glacial lake outburst floods (GLOFs) in high mountain areas, particularly if new lakes form in geomorphological setups prone to triggering events such as landslides or moraine collapses. We present the first complete inventory for future glacial lakes in High Mountain Asia by computing the subglacial bedrock for ~100 000 glaciers and estimating overdeepening area, volume and impact hazard for the larger potential lakes. We detect 25 285 overdeepenings larger than 104m2with a volume of 99.1 ± 28.6 km3covering an area of 2683 ± 773.8 km2. For the 2700 overdeepenings larger than 105m2, we assess the lake predisposition for mass-movement impacts that could trigger a GLOF by estimating the hazard of material detaching from surrounding slopes. Our findings indicate a shift in lake area, volume and GLOF hazard from the southwestern Himalayan region toward the Karakoram. The results of this study can be used for anticipating emerging threats and potentials connected to glacial lakes and as a basis for further studies at suspected GLOF hazard hotspots.
Telephone triage of suspected head and neck cancer patients during the coronavirus disease 2019 pandemic using the Head and Neck Cancer Risk Calculator version 2
Authors: Banerjee S , Voliotidis D , Parvin L , Rama S P K
Published: March 2021

Objective

Utilisation of the Head and Neck Cancer Risk Calculator version 2 has been recommended during the coronavirus disease 2019 pandemic for the assessment of head and neck cancer referrals. As limited data were available, this study was conducted to analyse the use of the Head and Neck Cancer Risk Calculator version 2 in clinical practice.

Method

Patients undergoing telephone triage in a two-week wait referral clinic were included. Data were collected and analysed using appropriate methods.

Results

Sixty-four patients in the study were risk-stratified into low-risk (51.6 per cent, 33 of 64), moderate-risk (14.1 per cent, 9 of 64) and high-risk (34.4 per cent, 22 of 64) groups. Of the patients, 53.1 per cent (34 of 64) avoided an urgent hospital visit, and 96.9 per cent (62 of 64) were cancer free, while 3.1 per cent (2 of 64) were found to have a head and neck malignancy. The sensitivity, specificity, negative predictive value and accuracy were 50.00 per cent, 66.13 per cent, 99.92 per cent and 66.11 per cent, respectively.

Conclusion

It is reasonable to use the calculator for triaging purposes, but it must always be accompanied by a meticulous clinical thought process.
Sexual reproductive strategies ofPuya nitida(Bromeliaceae) in a Colombian paramo, a tropical high-elevation ecosystem
Authors: Franco-Saldarriaga Alejandra , Bonilla-Gómez María Argenis
Published: March 2021

The low availability of pollinators in high-elevation ecosystems can lead to flowering plants showing different adaptive responses in order to assure their reproductive success. Shifts toward autogamy and asexual reproductive rates (the reproductive assurance hypothesis) and the compensatory measures to maintain outcrossing such as flower longevity and more prolonged pistil receptivity (the increased pollination probability hypothesis) are some of these responses. Several studies have tested both hypotheses, but investigations of plants of tropical alpine environments such as paramos that support these assumptions are still scarce.Puya nitida, an endemic Colombian plant species distributed in the paramo and subparamo in the Eastern Cordillera of Cundinamarca department, was used as a case study to test its reproductive characteristics that assure its sexual reproduction. We analysed the species’ floral morphology and development, its phenological patterns and its plant mating-system. We found thatPuya nitidashowed floral characteristics that promote pollination by birds, herkogamy and dichogamy, flowers and receptive stigmas with 9 and 12 days of longevity, respectively and an index of self-incompatibility that shows that it is mostly self-incompatible. We found a synchronic phenological pattern with an annual frequency and an intermediate duration with a peak in the period of lowest rainfall. Our results suggested that longer floral development, prolonged stigma receptivity, herkogamy and dichogamy and self-incompatibility might assure reproductive success, since the cross-pollination might be favoured when few pollinators are in attendance. Overall, these reproductive mechanisms add evidence to the increased pollination probability hypothesis, specifically for a plant species of a tropical high-elevation ecosystem where pollinators are scarce.
Impact of cardiovascular risk factors on myocardial work—insights from the STAAB cohort study
Authors: Sahiti Floran , Morbach Caroline , Cejka Vladimir , Tiffe Theresa , Wagner Martin , Eichner Felizitas A. , Gelbrich Götz , Heuschmann Peter U. , Störk Stefan
Published: March 2021

Myocardial work is a new echocardiography-based diagnostic tool, which allows to quantify left ventricular performance based on pressure–strain loops, and has been validated against invasively derived pressure–volume measurements. Myocardial work is described by its components (global constructive work [GCW], global wasted work [GWW]) and indices (global work index [GWI], global work efficiency [GWE]). Applying this innovative concept, we characterized the prevalence and severity of subclinical left ventricular compromise in the general population and estimated its association with cardiovascular (CV) risk factors. Within the Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study we comprehensively phenotyped a representative sample of the population of Würzburg, Germany, aged 30–79 years. Indices of myocardial work were determined in 1929 individuals (49.3% female, mean age 54 ± 12 years). In multivariable analysis, hypertension was associated with a mild increase in GCW, but a profound increase in GWW, resulting in higher GWI and lower GWE. All other CV risk factors were associated with lower GCW and GWI, but not with GWW. The association of hypertension and obesity with GWI was stronger in women. We conclude that traditional CV risk factors impact selectively and gender-specifically on left ventricular myocardial performance, independent of systolic blood pressure. Quantifying active systolic and diastolic compromise by derivation of myocardial work advances our understanding of pathophysiological processes in health and cardiac disease.
Regulation of mating genes during arbuscular mycorrhizal isolate co-existence—where is the evidence?
Authors: Malar C Mathu , Roux Christophe , Corradi Nicolas
Published: March 2021

A recent study published by Mateus et al. [1] claimed that 18 “mating-related” genes are differentially expressed in the model arbuscular mycorrhizal fungus (AMF) Rhizophagus irregularis when genetically distinct fungal strains co-colonize a host plant. To clarify the level of evidence for this interesting conclusion, we first aimed to validate the functional annotation of these 18 R. irregularis genes using orthology predictions. These analyses revealed that, although sequence relationship exists, only 2 of the claimed 18 R. irregularis mating genes are potential orthologues to validated fungal mating genes. We also investigated the RNA-seq data from Mateus et al. [1] using classical RNA-seq methods and statistics. This analysis found that the over-expression during strain co-existence was not significant at the typical cut-off of the R. irregularis strains DAOM197198 and B1 in plants. Overall, we do not find convincing evidence that the genes involved have functions in mating, or that they are reproducibly up or down regulated during co-existence in plants.
Inhomogeneous Kondo-lattice in geometrically frustrated Pr2Ir2O7
Authors: Kavai Mariam , Friedman Joel , Sherman Kyle , Gong Mingda , Giannakis Ioannis , Hajinazar Samad , Hu Haoyu , Grefe Sarah E. , Leshen Justin , Yang Qiu , Nakatsuji Satoru , Kolmogorov Aleksey N. , Si Qimiao , Lawler Michael , Aynajian Pegor
Published: March 2021

Magnetic fluctuations induced by geometric frustration of local Ir-spins disturb the formation of long-range magnetic order in the family of pyrochlore iridates. As a consequence, Pr2Ir2O7 lies at a tuning-free antiferromagnetic-to-paramagnetic quantum critical point and exhibits an array of complex phenomena including the Kondo effect, biquadratic band structure, and metallic spin liquid. Using spectroscopic imaging with the scanning tunneling microscope, complemented with machine learning, density functional theory and theoretical modeling, we probe the local electronic states in Pr2Ir2O7 and find an electronic phase separation. Nanoscale regions with a well-defined Kondo resonance are interweaved with a non-magnetic metallic phase with Kondo-destruction. These spatial nanoscale patterns display a fractal geometry with power-law behavior extended over two decades, consistent with being in proximity to a critical point. Our discovery reveals a nanoscale tuning route, viz. using a spatial variation of the electronic potential as a means of adjusting the balance between Kondo entanglement and geometric frustration.
Applications, challenges, and needs for employing synthetic biology beyond the lab
Authors: Brooks Sierra M. , Alper Hal S.
Published: March 2021

Synthetic biology holds great promise for addressing global needs. However, most current developments are not immediately translatable to ‘outside-the-lab’ scenarios that differ from controlled laboratory settings. Challenges include enabling long-term storage stability as well as operating in resource-limited and off-the-grid scenarios using autonomous function. Here we analyze recent advances in developing synthetic biological platforms for outside-the-lab scenarios with a focus on three major application spaces: bioproduction, biosensing, and closed-loop therapeutic and probiotic delivery. Across the Perspective, we highlight recent advances, areas for further development, possibilities for future applications, and the needs for innovation at the interface of other disciplines.
Uncontrolled asthma: a retrospective cohort study in Japanese patients newly prescribed with medium-/high-dose ICS/LABA
Authors: Inoue Hiromasa , Milligan Ki Lee , McConnon Aine , Yoshisue Hajime , Loefroth Emil , McSharry Martin , Yokoyama Akihito , Ichinose Masakazu
Published: March 2021

Many asthma patients remain uncontrolled despite guideline-based therapies. We examined real-life asthma control in Japanese patients prescribed with inhaled corticosteroid/long-acting β2-agonist (ICS/LABA). Patients (≥12 years) with ≥2 asthma diagnoses, newly initiated on medium-/high-dose ICS/LABA (Japanese asthma guidelines), from 01 April 2009 to 31 March 2015 were included, using Japan Medical Data Center Claims Database. Primary objective: proportion of patients with uncontrolled asthma in the year following ICS/LABA initiation. Secondary objectives: predictors of uncontrolled asthma and healthcare resource utilization. In medium-dose (N = 24,937) and high-dose (N = 8661) ICS/LABA cohorts, 23% and 21% patients, respectively, were uncontrolled. Treatment step up and exacerbation were most common indicators of uncontrolled asthma. Predictors of uncontrolled asthma, analyzed by multivariable Cox model, included systemic corticosteroid use, exacerbation history, comorbidities, and being female. In both cohorts, healthcare resource utilization was higher in patients with uncontrolled asthma. Over 20% patients with persistent asthma who initiated medium- or high-dose ICS/LABA were uncontrolled, highlighting unmet need for novel therapies in these patients.
Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses
Authors: Allen James D. , Ross Ted M.
Published: March 2021

While vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.
Superimposed gratings induce diverse response patterns of gamma oscillations in primary visual cortex
Authors: Wang Bin , Han Chuanliang , Wang Tian , Dai Weifeng , Li Yang , Yang Yi , Yang Guanzhong , Zhong Lvyan , Zhang Yange , Wu Yujie , Wang Gang , Yu Hongbo , Xing Dajun
Published: March 2021

Stimulus-dependence of gamma oscillations (GAMMA, 30–90 Hz) has not been fully understood, but it is important for revealing neural mechanisms and functions of GAMMA. Here, we recorded spiking activity (MUA) and the local field potential (LFP), driven by a variety of plaids (generated by two superimposed gratings orthogonal to each other and with different contrast combinations), in the primary visual cortex of anesthetized cats. We found two distinct narrow-band GAMMAs in the LFPs and a variety of response patterns to plaids. Similar to MUA, most response patterns showed that the second grating suppressed GAMMAs driven by the first one. However, there is only a weak site-by-site correlation between cross-orientation interactions in GAMMAs and those in MUAs. We developed a normalization model that could unify the response patterns of both GAMMAs and MUAs. Interestingly, compared with MUAs, the GAMMAs demonstrated a wider range of model parameters and more diverse response patterns to plaids. Further analysis revealed that normalization parameters for high GAMMA, but not those for low GAMMA, were significantly correlated with the discrepancy of spatial frequency between stimulus and sites’ preferences. Consistent with these findings, normalization parameters and diversity of high GAMMA exhibited a clear transition trend and region difference between area 17 to 18. Our results show that GAMMAs are also regulated in the form of normalization, but that the neural mechanisms for these normalizations might differ from those of spiking activity. Normalizations in different brain signals could be due to interactions of excitation and inhibitions at multiple stages in the visual system.
Curcumin promotes oligodendrocyte differentiation and their protection against TNF-α through the activation of the nuclear receptor PPAR-γ
Authors: Bernardo Antonietta , Plumitallo Cristina , De Nuccio Chiara , Visentin Sergio , Minghetti Luisa
Published: March 2021

Curcumin is a compound found in the rhizome of Curcuma longa (turmeric) with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. The current study aims to assess the effects of this natural compound on oligodendrocyte progenitor (OP) differentiation, particularly in inflammatory conditions. We found that curcumin can promote the differentiation of OPs and to counteract the maturation arrest of OPs induced by TNF-α by a mechanism involving PPAR-γ (peroxisome proliferator activated receptor), a ligand-activated transcription factor with neuroprotective and anti-inflammatory capabilities. Furthermore, curcumin induces the phosphorylation of the protein kinase ERK1/2 known to regulate the transition from OPs to immature oligodendrocytes (OLs), by a mechanism only partially dependent on PPAR-γ. Curcumin is also able to raise the levels of the co-factor PGC1-α and of the cytochrome c oxidase core protein COX1, even when OPs are exposed to TNF-α, through a PPAR-γ-mediated mechanism, in line with the known ability of PPAR-γ to promote mitochondrial integrity and functions, which are crucial for OL differentiation to occur. Altogether, this study provides evidence for a further mechanism of action of curcumin besides its well-known anti-inflammatory properties and supports the suggested therapeutic potential of this nutraceutical in demyelinating diseases.
Identifying gene expression patterns associated with drug-specific survival in cancer patients
Authors: Neary Bridget , Zhou Jie , Qiu Peng
Published: March 2021

The ability to predict the efficacy of cancer treatments is a longstanding goal of precision medicine that requires improved understanding of molecular interactions with drugs and the discovery of biomarkers of drug response. Identifying genes whose expression influences drug sensitivity can help address both of these needs, elucidating the molecular pathways involved in drug efficacy and providing potential ways to predict new patients’ response to available therapies. In this study, we integrated cancer type, drug treatment, and survival data with RNA-seq gene expression data from The Cancer Genome Atlas to identify genes and gene sets whose expression levels in patient tumor biopsies are associated with drug-specific patient survival using a log-rank test comparing survival of patients with low vs. high expression for each gene. This analysis was successful in identifying thousands of such gene–drug relationships across 20 drugs in 14 cancers, several of which have been previously implicated in the respective drug’s efficacy. We then clustered significant genes based on their expression patterns across patients and defined gene sets that are more robust predictors of patient outcome, many of which were significantly enriched for target genes of one or more transcription factors, indicating several upstream regulatory mechanisms that may be involved in drug efficacy. We identified a large number of genes and gene sets that were potentially useful as transcript-level biomarkers for predicting drug-specific patient survival outcome. Our gene sets were robust predictors of drug-specific survival and our results included both novel and previously reported findings, suggesting that the drug-specific survival marker genes reported herein warrant further investigation for insights into drug mechanisms and for validation as biomarkers to aid cancer therapy decisions.
A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis
Authors: Gabriel Emmanuel M. , Kim Minhyung , Fisher Daniel T. , Mangum Catherine , Attwood Kristopher , Ji Wenyan , Mukhopadhyay Debabrata , Bagaria Sanjay P. , Robertson Matthew W. , Dinh Tri A. , Knutson Keith L. , Skitzki Joseph J. , Wallace Michael B.
Published: March 2021

Aberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC). During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).
Ab initio study of the structure, elastic, and electronic properties of Ti3(Al1−nSin)C2 layered ternary compounds
Authors: Ahams S. T. , Shaari A. , Ahmed R. , Pattah N. F. Abdul , Idris M. C. , Haq B. U.
Published: March 2021

The MAX phase materials such as layered ternary carbides that simultaneously exhibit characteristics of metallic and ceramic materials have received substantial interest in recent years. Here, we present a systematic investigation of the electronic, structural stabilities, and elastic properties of Ti3(Al1−nSin)C2 (n = 0,1) MAX phase materials using the ab initio method via a plane-wave pseudopotential approach within generalized-gradient-approximations. The computed electronic band structures and projected density of states show that both Ti3SiC2 and Ti3AlC2 are metallic materials with a high density of states at the Fermi level emanating mainly from Ti-3d. Using the calculated elastic constants, the mechanical stability of the compounds was confirmed following the Born stability criteria for hexagonal structures. The Cauchy pressure and the Pugh’s ratio values establish the brittle nature of the Ti3SiC2 and Ti3AlC2 MAX phase materials. Due to their intriguing physical properties, these materials are expected to be suitable for applications such as thermal shock refractories and electrical contact coatings.
COVID-19 in South Africa: outbreak despite interventions
Authors: Schröder Malte , Bossert Andreas , Kersting Moritz , Aeffner Sebastian , Coetzee Justin , Timme Marc , Schlüter Jan
Published: March 2021

The future dynamics of the Corona Virus Disease 2019 (COVID-19) outbreak in African countries is largely unclear. Simultaneously, required strengths of intervention measures are strongly debated because containing COVID-19 in favor of the weak health care system largely conflicts with socio-economic hardships. Here we analyze the impact of interventions on outbreak dynamics for South Africa, exhibiting the largest case numbers across sub-saharan Africa, before and after their national lockdown. Past data indicate strongly reduced but still supracritical growth after lockdown. Moreover, large-scale agent-based simulations given different future scenarios for the Nelson Mandela Bay Municipality with 1.14 million inhabitants, based on detailed activity and mobility survey data of about 10% of the population, similarly suggest that current containment may be insufficient to not overload local intensive care capacity. Yet, enduring, slightly stronger or more specific interventions, combined with sufficient compliance, may constitute a viable option for interventions for South Africa.
Numerical simulation of wind field and sand flux in crescentic sand dunes
Authors: Zhang Huiwen , Wu Zhen , Hu Jing , Zhang Zhiping , Xiao Bin , Ma Jianping
Published: March 2021

Sand flux is the key factor to determine the migration of sand dunes and the erosion to the surrounding environment. There are crescent-shaped sand dunes of various scales in the desert, and there are significant differences in spatial wind field and sand flux among them. However, due to the difficulty of monitoring, it is difficult to continuously observe the spatial wind field and sand flux around the larger crescentic dunes. On the basis of the Reynolds-Average Navier–Stokes (RA-NS) equation and the stress and sand flux model, the distribution of wind field and sand flux of a circular dune with a height of 4.2 m and a length of about 100 m during the four evolutionary periods of the evolution into a crescentic dune was simulated in this study. By comparing with the measured results, we verified that the closer to the leeward side, the more the simulated values of the velocity in wind field and sand flux were in line with the measured results. In order to further analyze the influence of the height of dune and other relevant parameters on sand flux, we simulated the influence on wind field and sand flux by changing the air viscosity and wind velocity of upper boundary. We found that the air viscosity mainly affected the amount of deposited sand on the leeward side of sand dune, while the increase of wind velocity would undoubtedly increase the sand flux of the whole sand dune. In addition, the simulation results also showed that the influence of changes in height of dune on the turbulent intensity of leeward side was very significant, and the turbulent intensity increased with the height of dune. The height changes of tall dunes gradually affected the transport of sand caused by wind flow behind the leeward side because that the rotation of the wind flow would form new vortexes at the large pores behind the leeward side, which would increase the turbulent energy in space and thus would increase the distance of migration of the lifting sand. While the low sand dunes could not form extra small vortexes at the bottom of the leeward side, so the wind velocity was small and the eddy currents behind the leeward side were more stable. The simulation results indicated that wind velocity was not the only reason for increasing the amount of sand flux, and the fluctuation of wind flow caused by turbulence could also stimulate the movement of sand particles on the ground.