bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying multiple sclerosis subtypes using unsupervised machine learning and MRI data
Authors: Eshaghi Arman , Young Alexandra L. , Wijeratne Peter A. , Prados Ferran , Arnold Douglas L. , Narayanan Sridar , Guttmann Charles R. G. , Barkhof Frederik , Alexander Daniel C. , Thompson Alan J. , Chard Declan , Ciccarelli Olga
Published: April 2021

Multiple sclerosis (MS) can be divided into four phenotypes based on clinical evolution. The pathophysiological boundaries of these phenotypes are unclear, limiting treatment stratification. Machine learning can identify groups with similar features using multidimensional data. Here, to classify MS subtypes based on pathological features, we apply unsupervised machine learning to brain MRI scans acquired in previously published studies. We use a training dataset from 6322 MS patients to define MRI-based subtypes and an independent cohort of 3068 patients for validation. Based on the earliest abnormalities, we define MS subtypes as cortex-led, normal-appearing white matter-led, and lesion-led. People with the lesion-led subtype have the highest risk of confirmed disability progression (CDP) and the highest relapse rate. People with the lesion-led MS subtype show positive treatment response in selected clinical trials. Our findings suggest that MRI-based subtypes predict MS disability progression and response to treatment and may be used to define groups of patients in interventional trials.
Global influence of mantle temperature and plate thickness on intraplate volcanism
Authors: Ball P. W. , White N. J. , Maclennan J. , Stephenson S. N.
Published: April 2021

The thermochemical structure of lithospheric and asthenospheric mantle exert primary controls on surface topography and volcanic activity. Volcanic rock compositions and mantle seismic velocities provide indirect observations of this structure. Here, we compile and analyze a global database of the distribution and composition of Neogene-Quaternary intraplate volcanic rocks. By integrating this database with seismic tomographic models, we show that intraplate volcanism is concentrated in regions characterized by slow upper mantle shear-wave velocities and by thin lithosphere (i.e. <100 km). We observe a negative correlation between shear-wave velocities at depths of 125–175 km and melt fractions inferred from volcanic rock compositions. Furthermore, mantle temperature and lithospheric thickness estimates obtained by geochemical modeling broadly agree with values determined from tomographic models that have been converted into temperature. Intraplate volcanism often occurs in regions where uplifted (but undeformed) marine sedimentary rocks are exposed. Regional elevation of these rocks can be generated by a combination of hotter asthenosphere and lithospheric thinning. Therefore, the distribution and composition of intraplate volcanic rocks through geologic time will help to probe past mantle conditions and surface processes.
Ferroptosis response segregates small cell lung cancer (SCLC) neuroendocrine subtypes
Authors: Bebber Christina M. , Thomas Emily S. , Stroh Jenny , Chen Zhiyi , Androulidaki Ariadne , Schmitt Anna , Höhne Michaela N. , Stüker Lukas , de Pádua Alves Cleidson , Khonsari Armin , Dammert Marcel A. , Parmaksiz Fatma , Tumbrink Hannah L. , Beleggia Filippo , Sos Martin L. , Riemer Jan , George Julie , Brodesser Susanne , Thomas Roman K. , Reinhardt H. Christian , von Karstedt Silvia
Published: April 2021

Loss of TP53 and RB1 in treatment-naïve small cell lung cancer (SCLC) suggests selective pressure to inactivate cell death pathways prior to therapy. Yet, which of these pathways remain available in treatment-naïve SCLC is unknown. Here, through systemic analysis of cell death pathway availability in treatment-naïve SCLC, we identify non-neuroendocrine (NE) SCLC to be vulnerable to ferroptosis through subtype-specific lipidome remodeling. While NE SCLC is ferroptosis resistant, it acquires selective addiction to the TRX anti-oxidant pathway. In experimental settings of non-NE/NE intratumoral heterogeneity, non-NE or NE populations are selectively depleted by ferroptosis or TRX pathway inhibition, respectively. Preventing subtype plasticity observed under single pathway targeting, combined treatment kills established non-NE and NE tumors in xenografts, genetically engineered mouse models of SCLC and patient-derived cells, and identifies a patient subset with drastically improved overall survival. These findings reveal cell death pathway mining as a means to identify rational combination therapies for SCLC.
Computational high-throughput screening of alloy nanoclusters for electrocatalytic hydrogen evolution
Authors: Mao Xinnan , Wang Lu , Xu Yafeng , Wang Pengju , Li Youyong , Zhao Jijun
Published: April 2021

Here, we report a density functional theory (DFT)-based high-throughput screening method to successfully identify a type of alloy nanoclusters as the electrocatalyst for hydrogen evolution reaction (HER). Totally 7924 candidates of Cu-based alloy clusters of Cu55-nMn (M = Co, Ni, Ru, and Rh) are optimized and evaluated to screening for the promising catalysts. By comparing different structural patterns, Cu-based alloy clusters prefer the core–shell structures with the dopant metal in the core and Cu as the shell atoms. Generally speaking, the HER performance of the Cu-based nanoclusters can be significantly improved by doping transition metals, and the active sites are the bridge sites and three-fold sites on the outer-shell Cu atoms. Considering the structural stability and the electrochemical activity, core–shell CuNi alloy clusters are suggested to be the superior electrocatalyst for hydrogen evolution. A descriptor composing of surface charge is proposed to efficiently evaluate the HER activity of the alloy clusters supported by the DFT calculations and machine-learning techniques. Our screening strategy could accelerate the pace of discovery for promising HER electrocatalysts using metal alloy nanoclusters.
Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen
Authors: Bender Nicole G. , Khare Prachi , Martinez Juan , Tweedell Rebecca E. , Nyasembe Vincent O. , López-Gutiérrez Borja , Tripathi Abhai , Miller Dustin , Hamerly Timothy , Vela Eric M. , Davis Ryan R. , Howard Randall F. , Nsango Sandrine , Cobb Ronald R. , Harbers Matthias , Dinglasan Rhoel R.
Published: April 2021

Malaria transmission-blocking vaccines (TBVs) prevent the completion of the developmental lifecycle of malarial parasites within the mosquito vector, effectively blocking subsequent infections. The mosquito midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is the leading, mosquito-based TBV antigen. Structure-function studies identified two Class II epitopes that can induce potent transmission-blocking (T-B) antibodies, informing the design of the next-generation AnAPN1. Here, we functionally screened new immunogens and down-selected to the UF6b construct that has two glycine-linked copies of the T-B epitopes. We then established a process for manufacturing UF6b and evaluated in outbred female CD1 mice the immunogenicity of the preclinical product with the human-safe adjuvant Glucopyranosyl Lipid Adjuvant in a liposomal formulation with saponin QS21 (GLA-LSQ). UF6b:GLA-LSQ effectively immunofocused the humoral response to one of the key T-B epitopes resulting in potent T-B activity, underscoring UF6b as a prime TBV candidate to aid in malaria elimination and eradication efforts.
The effect of calcium and magnesium on activity, immunogenicity, and efficacy of a recombinant N1/N2 neuraminidase vaccine
Authors: Giurgea Luca T. , Park Jae-Keun , Walters Kathie-Anne , Scherler Kelsey , Cervantes-Medina Adriana , Freeman Ashley , Rosas Luz Angela , Kash John C. , Taubenberger Jeffery K. , Memoli Matthew J.
Published: April 2021

Despite the importance of immunity against neuraminidase (NA), NA content and immunogenicity are neglected in current influenza vaccines. To address this, a recombinant N1/N2 NA vaccine (NAV) was developed. Stability assays were used to determine optimal temperature and buffer conditions for vaccine storage. The effect of divalent cation-related enhancement of NA stability and activity on N1 and N2 immunogenicity and efficacy against viral challenge was assessed. Differences in activity between N1 and N2 and cation-related activity enhancement did not translate into differences in immunogenicity or efficacy. NAV-vaccinated mice showed robust antibody titers against N1 and N2, and after challenge with influenza A (H1N1) virus, decreased viral titers and decreased antiviral and inflammatory responses by transcriptomic analysis. These findings provide guidance for optimal storage and assessment of NA-based vaccines and confirm the importance of NA in influenza vaccination strategies in attenuating viral replication and limiting inflammatory responses necessary to clear infection.
A scenario modeling pipeline for COVID-19 emergency planning
Authors: Lemaitre Joseph C. , Grantz Kyra H. , Kaminsky Joshua , Meredith Hannah R. , Truelove Shaun A. , Lauer Stephen A. , Keegan Lindsay T. , Shah Sam , Wills Josh , Kaminsky Kathryn , Perez-Saez Javier , Lessler Justin , Lee Elizabeth C.
Published: April 2021

Coronavirus disease 2019 (COVID-19) has caused strain on health systems worldwide due to its high mortality rate and the large portion of cases requiring critical care and mechanical ventilation. During these uncertain times, public health decision makers, from city health departments to federal agencies, sought the use of epidemiological models for decision support in allocating resources, developing non-pharmaceutical interventions, and characterizing the dynamics of COVID-19 in their jurisdictions. In response, we developed a flexible scenario modeling pipeline that could quickly tailor models for decision makers seeking to compare projections of epidemic trajectories and healthcare impacts from multiple intervention scenarios in different locations. Here, we present the components and configurable features of the COVID Scenario Pipeline, with a vignette detailing its current use. We also present model limitations and active areas of development to meet ever-changing decision maker needs.
Unsteady thermal Maxwell power law nanofluid flow subject to forced thermal Marangoni Convection
Authors: Jawad Muhammad , Saeed Anwar , Gul Taza , Shah Zahir , Kumam Poom
Published: April 2021

In the current work, the unsteady thermal flow of Maxwell power-law nanofluid with Welan gum solution on a stretching surface has been considered. The flow is also exposed to Joule heating and magnetic effects. The Marangoni convection equation is also proposed for current investigation in light of the constitutive equations for the Maxwell power law model. For non-dimensionalization, a group of similar variables has been employed to obtain a set of ordinary differential equations. This set of dimensionless equations is then solved with the help of the homotopy analysis method (HAM). It has been established in this work that, the effects of momentum relaxation time upon the thickness of the film is quite obvious in comparison to heat relaxation time. It is also noticed in this work that improvement in the Marangoni convection process leads to a decline in the thickness of the fluid’s film.
Strain driven emergence of topological non-triviality in YPdBi thin films
Authors: Bhardwaj Vishal , Bhattacharya Anupam , Srivastava Shivangi , Khovaylo Vladimir V. , Sannigrahi Jhuma , Banerjee Niladri , Mani Brajesh K. , Chatterjee Ratnamala
Published: April 2021

Half-Heusler compounds exhibit a remarkable variety of emergent properties such as heavy-fermion behaviour, unconventional superconductivity and magnetism. Several of these compounds have been predicted to host topologically non-trivial electronic structures. Remarkably, recent theoretical studies have indicated the possibility to induce non-trivial topological surface states in an otherwise trivial half-Heusler system by strain engineering. Here, using magneto-transport measurements and first principles DFT-based simulations, we demonstrate topological surface states on strained [110] oriented thin films of YPdBi grown on (100) MgO. These topological surface states arise in an otherwise trivial semi-metal purely driven by strain. Furthermore, we observe the onset of superconductivity in these strained films highlighting the possibility of engineering a topological superconducting state. Our results demonstrate the critical role played by strain in engineering novel topological states in thin film systems for developing next-generation spintronic devices.
Monocarborane cluster as a stable fluorine-free calcium battery electrolyte
Authors: Kisu Kazuaki , Kim Sangryun , Shinohara Takara , Zhao Kun , Züttel Andreas , Orimo Shin-ichi
Published: April 2021

High-energy-density and low-cost calcium (Ca) batteries have been proposed as ‘beyond-Li-ion’ electrochemical energy storage devices. However, they have seen limited progress due to challenges associated with developing electrolytes showing reductive/oxidative stabilities and high ionic conductivities. This paper describes a calcium monocarborane cluster salt in a mixed solvent as a Ca-battery electrolyte with high anodic stability (up to 4 V vs. Ca2+/Ca), high ionic conductivity (4 mS cm−1), and high Coulombic efficiency for Ca plating/stripping at room temperature. The developed electrolyte is a promising candidate for use in room-temperature rechargeable Ca batteries.
Zbp1-positive cells are osteogenic progenitors in periodontal ligament
Authors: Ueda Tsugumi , Iwayama Tomoaki , Tomita Kiwako , Matsumoto Shuji , Iwashita Mizuho , Bhongsatiern Phan , Sakashita Hiromi , Fujihara Chiharu , Takedachi Masahide , Murakami Shinya
Published: April 2021

Periodontal ligament (PDL) possesses a stem/progenitor population to maintain the homeostasis of periodontal tissue. However, transcription factors that regulate this population have not yet been identified. Thus, we aimed to identify a molecule related to the osteogenic differentiation of PDL progenitors using a single cell-based strategy in this study. We first devised a new protocol to isolate PDL cells from the surface of adult murine molars and established 35 new single cell-derived clones from the PDL explant. Among these clones, six clones with high (high clones, n = 3) and low (low clones, n = 3) osteogenic potential were selected. Despite a clear difference in the osteogenic potential of these clones, no significant differences in their cell morphology, progenitor cell marker expression, alkaline phosphatase activity, proliferation rate, and differentiation-related gene and protein expression were observed. RNA-seq analysis of these clones revealed that Z-DNA binding protein-1 (Zbp1) was significantly expressed in the high osteogenic clones, indicating that Zbp1 could be a possible marker and regulator of the osteogenic differentiation of PDL progenitor cells. Zbp1-positive cells were distributed sparsely throughout the PDL. In vitro Zbp1 expression in the PDL clones remained at a high level during osteogenic differentiation. The CRISPR/Cas9 mediated Zbp1 knockout in the high clones resulted in a delay in cell differentiation. On the other hand, Zbp1 overexpression in the low clones promoted cell differentiation. These findings suggested that Zbp1 marked the PDL progenitors with high osteogenic potential and promoted their osteogenic differentiation. Clarifying the mechanism of differentiation of PDL cells by Zbp1 and other factors in future studies will facilitate a better understanding of periodontal tissue homeostasis and repair, possibly leading to the development of novel therapeutic measures.
How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight
Authors: Kuo Chien-Feng , Shi Leiyu , Lin Cheng-Li , Yao Wei-Cheng , Chen Hsiang-Ting , Lio Chon-Fu , Wang Yu-Ting Tina , Su Ching-Huang , Hsu Nai-Wei , Tsai Shin-Yi
Published: April 2021

Chronic Fatigue Syndrome (CFS) has been defined as unexplained relapsing or persistent fatigue for at least 6 consecutive months. Immuno-inflammatory pathway, bacterial infection, and other causes play essential roles in CFS. Helicobacter pylori infection is one of the most common causes of foregut inflammation, leading to peptic ulcer disease (PUD). This study aimed to analyze the risk of CFS development between patients with and without PUD. Other related factors were also analyzed. We performed a retrospective, nationwide cohort study identifying patients with or without PUD respectively by analyzing the Longitudinal Health Insurance Database 2000 (LHID2000), Taiwan. The overall incidence of CFS was higher in the PUD cohort than in the non- PUD cohort (HR = 2.01, 95% CI = 1.75–2.30), with the same adjusted HR (aHR) when adjusting for age, sex, and comorbidities. The sex-specific PUD cohort to the non-PUD cohort relative risk of CFS was significant in both genders. The age-specific incidence of CFS showed incidence density increasing with age in both cohorts. There is an increased risk of developing CFS following PUD, especially in females and the aging population. Hopefully, these findings can prevent common infections from progressing to debilitating, chronic conditions such as CFS.
Plasma bilirubin levels are reduced in first-episode psychosis patients and associates to working memory and duration of untreated psychosis
Authors: Becklén Meneca , Orhan Funda , Piehl Fredrik , Cervenka Simon , Sellgren Carl M. , Flyckt Lena , Erhardt Sophie , Fatouros-Bergman Helena
Published: April 2021

Schizophrenia is a severe mental disorder and one of its characteristics is cognitive impairments. Findings regarding levels of the heme metabolite and plasma antioxidant bilirubin in schizophrenia are inconclusive. However, a recently published study indicate that low levels of bilirubin may be implicated in the memory impairments seen in the disorder. The aim of this cross-sectional study was to investigate the levels of bilirubin in individuals with a first-episode psychosis (FEP) and to examine if bilirubin levels were associated to cognitive impairments, symptoms and duration of untreated psychosis (DUP). Bilirubin levels were reduced in 39 individuals with FEP compared with 20 HC (median [IQR]: 11.0 [9.0–13.0] µM vs. 15.0 [11.5–18.5] µM). In individuals with FEP, bilirubin levels were also positively correlated to two working memory tests (r = 0.40 and r = 0.32) and inversely correlated to DUP (r = − 0.36). Findings were not influenced by confounding factors. The results confirm the antioxidant deficit previously seen in schizophrenia, but also indicate that these changes may be related to DUP. The study also confirms that bilirubin may be implicated in the cognitive deficits that accompanies the disorder, here for the first time presented in individuals with FEP.
Author Correction: Aortic acceleration as a noninvasive index of left ventricular contractility in the mouse
Authors: Tovar Perez Jorge Enrique , Ortiz-Urbina Jesus , Heredia Celia Pena , Pham Thuy T. , Madala Sridhar , Hartley Craig J. , Entman Mark L. , Taffet George E. , Reddy Anilkumar K.
Published: April 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Functional traits linked to pathogen prevalence in wild bee communities
Authors: Figueroa Laura L. , Compton Sally , Grab Heather , McArt Scott H.
Published: April 2021

Reports of pollinator declines have prompted efforts to understand contributing factors and protect vulnerable species. While pathogens can be widespread in bee communities, less is known about factors shaping pathogen prevalence among species. Functional traits are often used to predict susceptibility to stressors, including pathogens, in other species-rich communities. Here, we evaluated the relationship between bee functional traits (body size, phenology, nesting location, sociality, and foraging choice) and prevalence of trypanosomes, neogregarines, and the microsporidian Nosema ceranae in wild bee communities. For the most abundant bee species in our system, Bombus impatiens, we also evaluated the relationship between intra-specific size variation and pathogen prevalence. A trait-based model fit the neogregarine prevalence data better than a taxa-based model, while the taxonomic model provided a better model fit for N. ceranae prevalence, and there was no marked difference between the models for trypanosome prevalence. We found that Augochlorella aurata was more likely to harbor trypanosomes than many other bee taxa. Similarly, we found that bigger bees and those with peak activity later in the season were less likely to harbor trypanosomes, though the effect of size was largely driven by A. aurata. We found no clear intra-specific size patterns for pathogen prevalence in B. impatiens. These results indicate that functional traits are not always better than taxonomic affinity in predicting pathogen prevalence, but can help to explain prevalence depending on the pathogen in species-rich bee communities.
Risk factors for deep surgical site infection after posterior cervical spine surgery in adults: a multicentre observational cohort study
Authors: Ogihara Satoshi , Yamazaki Takashi , Shiibashi Michio , Chikuda Hirotaka , Maruyama Toru , Miyoshi Kota , Inanami Hirohiko , Oshima Yasushi , Azuma Seiichi , Kawamura Naohiro , Yamakawa Kiyofumi , Hara Nobuhiro , Morii Jiro , Okazaki Rentaro , Takeshita Yujiro , Nishimoto Junji , Tanaka Sakae , Saita Kazuo
Published: April 2021

Surgical site infection (SSI) is a serious complication following spine surgery and is correlated with significant morbidities, poor clinical outcomes, and increased healthcare costs. Accurately identifying risk factors can help develop strategies to reduce this devastating consequence; however, few multicentre studies have investigated risk factors for SSI following posterior cervical spine surgeries. Between July 2010 and June 2015, we performed an observational cohort study on deep SSI in adult patients who underwent posterior cervical spine surgery at 10 research hospitals. Detailed patient- and procedure-specific potential risk variables were prospectively recorded using a standardised data collection chart and were reviewed retrospectively. Among the 2184 consecutive adult patients enrolled, 28 (1.3%) developed postoperative deep SSI. Multivariable regression analysis revealed 2 statistically significant independent risk factors: occipitocervical surgery (P < 0.001) and male sex (P = 0.024). Subgroup analysis demonstrated that occipitocervical surgery (P = 0.001) was the sole independent risk factor for deep SSI in patients with instrumented fusion. Occipitocervical surgery is a relatively rare procedure; therefore, our findings were based on a large cohort acquired using a multicentre study. To the best of our knowledge, this is the first study to identify occipitocervical procedure as an independent risk variable for deep SSI after spinal surgery.
Testing average wind speed using sampling plan for Weibull distribution under indeterminacy
Authors: Aslam Muhammad
Published: April 2021

The time truncated plan for the Weibull distribution under the indeterminacy is presented. The plan parameters of the proposed plan are determined by fixing the indeterminacy parameter. The plan parameters are given for various values of indeterminacy parameters. From the results, it can be concluded that the values of sample size reduce as indeterminacy values increase. The application of the proposed plan is given using wind speed data. From the wind speed example, it is concluded that the proposed plan is helpful to test the average wind speed at smaller values of sample size as compared to existing sampling plan.
Immune checkpoint molecules B7-H6 and PD-L1 co-pattern the tumor inflammatory microenvironment in human breast cancer
Authors: Cherif Boutheina , Triki Hana , Charfi Slim , Bouzidi Lobna , Kridis Wala Ben , Khanfir Afef , Chaabane Kais , Sellami-Boudawara Tahya , Rebai Ahmed
Published: April 2021

B7-H6 and PD-L1 belong to the B7 family co-stimulatory molecules fine-tuning the immune response. The present work investigates the clinical effect of B7-H6 protein expression with PD-L1 status and the infiltration of natural killer cells as potential biomarkers in breast tumor inflammatory microenvironment. The expression levels of B7-H6 protein by cancer cells and immune infiltrating cells in human breast cancer tissues and evaluate their associations with PD-L1 expression, NK cell status, clinical pathological features and prognosis were explored. The immunohistochemistry labeling method was used to assess B7-H6 and PD-L1 proteins expression by cancer and immune cells. The associations between immune checkpoint, major clinical pathological variables and survival rates were analyzed. B7-H6 protein was depicted in both breast and immune cells. Results showed that Tumor B7-H6 expression is highly associated with Her-2 over expression. B7-H6 + immune cells are highly related to the Scarff–Bloom–Richardson grade and associated with PD-L1 expression and NK cells status. Survival analysis revealed a better prognosis in patients with low expression of B7-H6 by cancer cells. Conversely, B7-H6 + immune cells were significantly associated with longer survival. Findings strongly suggest an interaction between B7 molecules that contributes to a particular design of the inflammatory microenvironment. This may influence the efficiency of therapies based on antibodies blocking the PD-L1/PD1 pathway and can explain the detection of clinical benefits only in a fraction of patients treated with immune checkpoint inhibitors.
Synthesis of core–shell copper–graphite submicronic particles and carbon nano-onions by spark discharges in liquid hydrocarbons
Authors: Glad X. , Gorry J. , Cha M. S. , Hamdan A.
Published: April 2021

Spark discharge in hydrocarbon liquids is considered a promising method for the synthesis of various nanomaterials, including nanocomposites. In this study, copper–carbon particles were synthesized by generating spark discharges between two Cu electrodes immersed in heptane, cyclohexane, or toluene. The synthesized particles were characterized using scanning electron microscopy, high-resolution transmission electron microscopy, and selected area electron diffraction. Overall, two families of particles were observed: Cu particles (diameter < 10 nm) embedded in a carbon matrix and submicrometric Cu particles encapsulated in a carbon shell. The obtained results indicate that the size distribution of the Cu nanoparticles and the degree of graphitization of the carbon matrix depend on the liquid. Indeed, discharges in heptane lead to Cu particles with diameters of 2–6 nm embedded in a carbon matrix of low graphitization degree, while discharges in toluene result in particles with diameters of 2–14 nm embedded in carbon matrix of high graphitization degree. Based on the obtained experimental results, it is proposed that the Cu nanoparticles are produced in the plasma core where Cu (evaporated from the electrode surface) and carbonaceous species (decomposition of the liquid) are present. When the plasma hits the electrode surface, hot (thousands of Kelvin) Cu particles are ejected from the electrode, and they propagate in the liquid. The propagation of the hot particles in the liquid results in the local evaporation of this liquid, which leads to the formation of a C-shell around each Cu particle. In few cases where the shape of the Cu particle is not spherical, carbon nanoonions are detected between the C-shell and the Cu core. These nanoonions are supposedly formed under the effect of the fluid vortices generated close to the particle surfaces when these latter are ejected into the liquid.
Epidemiologic trends of infants with orofacial clefts in a multiethnic country: a retrospective population-based study
Authors: Yow Mimi , Jin Aizhen , Yeo George Seow Heong
Published: April 2021

Cleft births surveillance is essential in healthcare and prevention planning. Data are needed in precision medicine to target upstream management for at-risk individuals. This study characterizes Singapore’s population-based orofacial cleft topography by ethnicity and gender, and establishes the cleft cohort’s infant mortality rate. Data, in the decade 2003 to 2012, were extracted by the National Birth Defects Registry. Trend testing by linear regression was at p < 0.05 significance level. Prevalence per 10,000 for population-based cleft live births was 16.72 with no significant upward trend (p = 0.317). Prevalence rates were 8.77 in the isolated cleft group, 7.04 in the non-isolated cleft group, and 0.91 in the syndromic cleft group. There was significant upward trend in infants with non-isolated clefts (p = 0.0287). There were no significant upward trends in infants with isolated clefts and syndromic clefts. Prevalence rates were sexually dimorphic and ethnic-specific: male 17.72; female 15.78; Chinese group 17.17; Malay group 16.92; Indian group 10.74; and mixed ethnic origins group 21.73. The overall infant mortality rate (IMR) was 4.8% in the cohort of 608 cleft births, which was more than double the population-based IMR of 2.1% in the same period. Infants with non-isolated and syndromic clefts accounted for 96.6% of the deaths.
Post-synthesis nanostructuration of BSA-Capsaicin nanoparticles generated by sucrose excipient
Authors: Carriles Ramón , Zavala-García Laura E. , Nava-Coronel Sofía , Sánchez-Arreguín Alejandro , López Mercedes G. , Sánchez-Segura Lino
Published: April 2021

In the pharmaceutical industry nano-hydrocolloid systems frequently coalesce or present nanoparticle aggregation after a long storage periods. Besides, the lyophilization process used to dry nanoparticles (NPs) produces loss of their original properties after dispersion. In this work we evaluated the effect on morphology and physicochemical properties of different protective excipients during drying of bovine serum albumin (BSA) NPs loaded with different concentrations of capsaicin. Capsaicin concentrations of 0, 812, 1625, 2437, and 3250 µg mL−1 were used; subsequently, NPs were dried with deionized water (DW), NaCl (DN), sucrose (DS), and not dried (ND). We found that ND, DW, and DN treatments showed a negative effect on the NPs properties; while, DS reduced the aggregation and produced the formation of isolated nanoparticles at higher concentrations of capsaicin (3250 µg mL−1), improving their circular shape, morphometrical parameters, and ζ-potential. The stability of the BSA-capsaicin NPs was associated to complex capsaicin/amino acid/water, in which GLY/GLN, ALA/HIS, ARG, THR, TYR, and Iso/CYS amino acids are involved in the restructuration of capsaicin molecules into the surface of nanoparticles during the drying process. The secondary nanostructuration in the post-synthesis stage can improve the molecular stability of the particles and the capacity of entrapping hydrophobic drugs, like capsaicin.
Mechanical strength and flexibility in $$\alpha '$$-4H borophene
Authors: Mozvashi Shobair Mohammadi , Mohebpour Mohammad Ali , Vishkayi Sahar Izadi , Tagani Meysam Bagheri
Published: April 2021

Very recently, a novel phase of hydrogenated borophene, namely $$\alpha '$$

α
′

-4H, has been synthesized in a free-standing form. Unlike pure borophenes, this phase shows very good stability in the air environment and possesses semiconducting characteristics. Because of the interesting stiffness and flexibility of borophenes, herein, we systematically studied the mechanical properties of this novel hydrogenated phase. Our results show that the monolayer is stiffer (Y$$_\text {xy}$$

xy

= $$\sim $$
∼
195 N/m) than group IV and V 2D materials and even than MoS$$_2$$

2

, while it is softer than graphene. Moreover, similar to other phases of borophene, the inherent anisotropy of the pure monolayer increases with hydrogenation. The monolayer can bear biaxial, armchair, and zigzag strains up to 16, 10, and 14% with ideal strengths of approximately 14, 9, and 12 N/m, respectively. More interestingly, it can remain semiconductor under this range of tension. These outstanding results suggest that the $$\alpha '$$

α
′

-4H is a promising candidate for flexible nanoelectronics.
Quantifying surface morphology of manufactured activated carbon and the waste coffee grounds using the Getis-Ord-Gi* statistic and Ripley’s K function
Authors: Lee Sanghoon , Na Sukjoon , Rogers Olivia G. , Youn Sungmin
Published: April 2021

Activated carbon can be manufactured from waste coffee grounds via physical and/or chemical activation processes. However, challenges remain to quantify the differences in surface morphology between manufactured activated carbon granules and the waste coffee grounds. This paper presents a novel quantitative method to determine the quality of the physical and chemical activation processes performed in the presence of intensity inhomogeneity and identify surface characteristics of manufactured activated carbon granules and the waste coffee grounds. The spatial density was calculated by the Getis-Ord-Gi* statistic in scanning electron microscopy images. The spatial characteristics were determined by analyzing Ripley’s K function and complete spatial randomness. Results show that the method introduced in this paper is capable of distinguishing between manufactured activated carbon granules and the waste coffee grounds, in terms of surface morphology.
Enhanced anti-cancer activity of andrographis with oligomeric proanthocyanidins through activation of metabolic and ferroptosis pathways in colorectal cancer
Authors: Shimura Tadanobu , Sharma Priyanka , Sharma Geeta G. , Banwait Jasjit K. , Goel Ajay
Published: April 2021

The high degree of morbidity and mortality in colorectal cancer (CRC) patients is largely due to the development of chemoresistance against conventional chemotherapeutic drugs. In view of the accumulating evidence that various dietary botanicals offer a safe, inexpensive and multi-targeted treatment option, herein, we hypothesized that a combination of Andrographis paniculata and Oligomeric Proanthocyanidins (OPCs) might interact together with regard to anti-tumorigenic activity in CRC. As a result, we demonstrated the enhanced anti-cancer activity between these two botanical extracts in terms of their ability to inhibit cancer cell growth, suppress colony formation and induce apoptosis. Furthermore, we validated these findings in subcutaneous xenograft model and in patient derived primary epithelial 3D organoids. Transcriptomic profiling identified involvement of metabolic pathways and ferroptosis-associated genes, including HMOX1, GCLC and GCLM, that may be responsible for the increased anti-tumorigenic activity by the two compounds. Collectively, our study provides novel evidence in support of the combinatorial use of andrographis and OPCs as a potential therapeutic option, perhaps as an adjunctive treatment to classical drugs, in patients with colorectal cancer.
The fast response of Sahel precipitation to climate change allows effective mitigation action
Authors: Monerie Paul-Arthur , Pohl Benjamin , Gaetani Marco
Published: April 2021

Climate change will drive major perturbations of the West African summer monsoon. A zonal contrast in precipitation will develop at the end of the century, with an increase in precipitation over the central Sahel and a decrease in precipitation over the western Sahel. Such a zonal contrast results from the antagonist effects of the fast (due to enhanced radiative warming over land, and over the North Hemisphere, relative to the South Hemisphere) and slow (associated with long-term changes in oceanic circulation) responses of precipitation to increasing greenhouse gases. While such changes have already been assessed, less attention has been given to their temporality, an issue of major importance to promote efficient mitigation and adaptation measures. Here, we analyse the future evolution of precipitation changes decomposed into a fast and a slow response, showing that the fast response dominates the slow one. From this evidence, we highlight that mitigation strategies may be successful at reducing the effect of climate change on Sahel precipitation within a few decades, by muting the fast response. This decomposition also allows for a better understanding of the uncertainty of climate model predictions in Africa.
Chlorosulfuric acid-assisted production of functional 2D materials
Authors: Moazzami Gudarzi Mohsen , Asaad Maryana , Mao Boyang , Pinter Gergo , Guo Jianqiang , Smith Matthew , Zhong Xiangli , Georgiou Thanasis , Gorbachev Roman , Haigh Sarah J. , Novoselov Kostya S. , Kretinin Andrey V.
Published: April 2021

The use of two-dimensional materials in bulk functional applications requires the ability to fabricate defect-free 2D sheets with large aspect ratios. Despite huge research efforts, current bulk exfoliation methods require a compromise between the quality of the final flakes and their lateral size, restricting the effectiveness of the product. In this work, we describe an intercalation-assisted exfoliation route, which allows the production of high-quality graphene, hexagonal boron nitride, and molybdenum disulfide 2D sheets with average aspect ratios 30 times larger than that obtained via conventional liquid-phase exfoliation. The combination of chlorosulfuric acid intercalation with in situ pyrene sulfonate functionalisation produces a suspension of thin large-area flakes, which are stable in various polar solvents. The described method is simple and requires no special laboratory conditions. We demonstrate that these suspensions can be used for fabrication of laminates and coatings with electrical properties suitable for a number of real-life applications.
Digital health interventions in palliative care: a systematic meta-review
Authors: Finucane Anne M. , O’Donnell Hannah , Lugton Jean , Gibson-Watt Tilly , Swenson Connie , Pagliari Claudia
Published: April 2021

Digital health interventions (DHIs) have the potential to improve the accessibility and effectiveness of palliative care but heterogeneity amongst existing systematic reviews presents a challenge for evidence synthesis. This meta-review applied a structured search of ten databases from 2006 to 2020, revealing 21 relevant systematic reviews, encompassing 332 publications. Interventions delivered via videoconferencing (17%), electronic healthcare records (16%) and phone (13%) were most frequently described in studies within reviews. DHIs were typically used in palliative care for education (20%), symptom management (15%), decision-making (13%), information provision or management (13%) and communication (9%). Across all reviews, mostly positive impacts were reported on education, information sharing, decision-making, communication and costs. Impacts on quality of life and physical and psychological symptoms were inconclusive. Applying AMSTAR 2 criteria, most reviews were judged as low quality as they lacked a protocol or did not consider risk of bias, so findings need to be interpreted with caution.
Author Correction: Human stem cells home to and repair laser-damaged trabecular meshwork in a mouse model
Authors: Yun Hongmin , Wang Yiwen , Zhou Yi , Kumar Ajay , Wang Ke , Sun Ming , Stolz Donna B. , Xia Xiaobo , Ethier C. Ross , Du Yiqin
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s42003-021-01957-x
RNAi efficacy is enhanced by chronic dsRNA feeding in pollen beetle
Authors: Willow Jonathan , Soonvald Liina , Sulg Silva , Kaasik Riina , Silva Ana Isabel , Taning Clauvis Nji Tizi , Christiaens Olivier , Smagghe Guy , Veromann Eve
Published: April 2021

Double-stranded RNAs (dsRNAs) represent a promising class of biosafe insecticidal compounds. We examined the ability to induce RNA interference (RNAi) in the pollen beetle Brassicogethes aeneus via anther feeding, and compared short-term (3 d) to chronic (17 d) feeding of various concentrations of dsRNA targeting αCOP (dsαCOP). In short-term dsαCOP feeding, only the highest concentration resulted in significant reductions in B. aeneus survival; whereas in chronic dsαCOP feeding, all three concentrations resulted in significant mortality. Chronic dsαCOP feeding also resulted in significantly greater mortality compared to short-term feeding of equivalent dsαCOP concentrations. Our results have implications for the economics and development of dsRNA spray approaches for managing crop pests, in that multiple lower-concentration dsRNA spray treatments across crop growth stages may result in greater pest management efficacy, compared to single treatments using higher dsRNA concentrations. Furthermore, our results highlight the need for research into the development of RNAi cultivars for oilseed rape protection, given the enhanced RNAi efficacy resulting from chronic, compared to short-term, dsRNA feeding in B. aeneus.
Author Correction: Genomic insights of body plan transitions from bilateral to pentameral symmetry in Echinoderms
Authors: Li Yongxin , Omori Akihito , Flores Rachel L. , Satterfield Sheri , Nguyen Christine , Ota Tatsuya , Tsurugaya Toko , Ikuta Tetsuro , Ikeo Kazuho , Kikuchi Mani , Leong Jason C. K. , Reich Adrian , Hao Meng , Wan Wenting , Dong Yang , Ren Yaondong , Zhang Si , Zeng Tao , Uesaka Masahiro , Uchida Yui , Li Xueyan , Shibata Tomoko F. , Bino Takahiro , Ogawa Kota , Shigenobu Shuji , Kondo Mariko , Wang Fayou , Chen Luonan , Wessel Gary , Saiga Hidetoshi , Cameron R. Andrew , Livingston Brian , Bradham Cynthia , Wang Wen , Irie Naoki
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s42003-021-02005-4
Author Correction: Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A
Authors: Olivieri Cristina , Walker Caitlin , Karamafrooz Adak , Wang Yingjie , Manu V. S. , Porcelli Fernando , Blumenthal Donald K. , Thomas David D. , Bernlohr David A. , Simon Sanford M. , Taylor Susan S. , Veglia Gianluigi
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s42003-021-02006-3
Genistein suppresses allergic contact dermatitis through regulating the MAP2K2/ERK pathway
Authors: Xu Jinhong , Xiong Hui , Zhao Zhongqiu , Luo Miao , Ju Yankun , Yang Guangzhong , Mei Zhinan
Published: April 2021

Genistein, a flavonoid, is one of the main components of soybeans. It was shown to alleviate contact dermatitis through the inhibition of the allergen-induced activation of MAP2K2 in keratinocytes.
Ginseng ameliorates exercise-induced fatigue potentially by regulating the gut microbiota
Authors: Zhou Shan-Shan , Zhou Jing , Xu Jin-Di , Shen Hong , Kong Ming , Yip Ka-Man , Han Quan-Bin , Zhao Zhong-Zhen , Xu Jun , Chen Hu-Biao , Li Song-Lin
Published: April 2021

WEG showed strong anti-EF effects by the beneficial effects of saccharides and ginsenosides on gut microbiota, then energy metabolism abnormality, lipid peroxidation and metabolic disorder as well as inflammatory response.
Current advances in ultrasound-combined nanobubbles for cancer-targeted therapy: a review of the current status and future perspectives
Authors: Su Chunhong , Ren XiaoJun , Nie Fang , Li Tiangang , Lv Wenhao , Li Hui , Zhang Yao
Published: April 2021

NBs combined with ultrasound demonstrated the ability to enhance the targeting of anticancer agents and improve the efficacy.
Exploring the utility of hybrid siloxane-phosphocholine (SiPC) liposomes as drug delivery vehicles
Authors: Frampton Mark B. , Blais Andrea , Raczywolski Zachary , Castle Alan , Zelisko Paul M.
Published: April 2021

Hybrid siloxane-phosphocholines (SiPCs) are a unique class of lipids that spontaneously form unilamellar vesicles (ULVs) that are ∼100 nm in diameter upon exposure to aqueous media without the need for extrusion and can be used as delivery vehicles.
Mechanical power driven SPME-SERS ultra-fast detection of illegal additives in aquaculture water
Authors: Lv Handi , Guan Qi , Wang Ying , Zhang Xiaoli
Published: April 2021

A strategy combining mechanical power and integration of SPME-SERS detection based on a dual-function porous silver fiber was used to realize ultra-fast detection of illegal additives in aquaculture water (within 1 minute).
Effects of alternating current poling on the dielectric and piezoelectric properties of Pb(In0.5Nb0.5)O3–PbTiO3 crystals with a high Curie temperature
Authors: Xiong Junjie , Wang Zujian , Yang Xiaoming , Su Rongbing , Long Xifa , He Chao
Published: April 2021

The ε33T/ε0 and d33 values of ACP 0.66PIN–0.34PT crystals are shown to be 3070 and 1400 pC N−1, respectively, which are 14% and 18% larger than those of a DCP sample, owing to the enhancement of both intrinsic and extrinsic contributions.
Biradical o-iminobenzosemiquinonato(1−) complexes of nickel(ii): catalytic activity in three-component coupling of aldehydes, amines and alkynes
Authors: Nasibipour Mina , Safaei Elham , Moaddeli Ali , Masoumpour Marziyeh Sadat , Wojtczak Andrzej
Published: April 2021

The six-coordinated bis-o-iminosemiquinone complex, NiL2BIS, in which LBIS is the o-iminosemiquinone 1-electron oxidized form of the tridentate o-aminophenol benzoxazole-based ligand H2LBAP, was synthesized and characterized.
Calixarene based portable sensor for the direct assay of indiscriminate ephedrine content of weight loss herbal preparations
Authors: Wahba Mary E. , El Wasseef Dalia , Saad Ahmed S. , Draz Mohammed E.
Published: April 2021

Calixarene based solid-state potentiometric sensor for direct assay of indiscriminate ephedrine content in weight loss herbal products.
Small functionalized iron oxide nanoparticles for dual brain magnetic resonance imaging and fluorescence imaging
Authors: Wei Ruixue , Liu Yang , Gao Jinhao , Yong V. Wee , Xue Mengzhou
Published: April 2021

SIONs is modified with brain targeting ligands and photosensitizers, and is used for in vivo MR/FL dual-mode high-sensitivity brain imaging.
Controlling the aqueous growth of urea crystals with different growth inhibitors: a molecular-scale study
Authors: Singh M. K.
Published: April 2021

Effect of different growth additives on the aqueous growth of crystalline urea is investigated computationally at the different levels of supersaturation and additive concentration.
Applications of liquid crystals in biosensing
Authors: Wang Ziyihui , Xu Tianhua , Noel Adam , Chen Yu-Cheng , Liu Tiegen
Published: April 2021

Recent investigations on the design and application of liquid crystal-based biosensors have been reviewed, according to the phenomenon that orientations of liquid crystals can be directly influenced by interactions between biomolecules and liquid crystal molecules. With the ability to detect external stimuli with high sensitivity, liquid crystal biosensors can help realize a new biosensing era.
Recyclable, weldable, mechanically durable, and programmable liquid metal-elastomer composites
Authors: Chen Guokang , Deng Xiaobo , Zhu Lifei , Handschuh-Wang Stephan , Gan Tiansheng , Wang Ben , Wu Qixing , Fang Hui , Ren Nailin , Zhou Xuechang
Published: April 2021

Diels–Alder (DA) bond crosslinked polyurethane (PU) networks are utilized as a matrix to fabricate multifunctional liquid metal (LM)-elastomer composites.
Recent progress in natural product-based inhibitor screening with enzymatic fluorescent probes
Authors: Chen Yi
Published: April 2021

In this mini review, small-molecule based enzymatic fluorescent probes for natural inhibitor screening has been discussed, which includes the construction and sensing mechanisms of developed probes and their applications in inhibitor screening.
Fast detection of E. coli with a novel fluorescent biosensor based on a FRET system between UCNPs and GO@Fe3O4 in urine specimens
Authors: Yao Yuan , Xie Guoming , Zhang Xin , Yuan Jinshan , Hou Yulei , Chen Hui
Published: April 2021

As detection signal, UCNP fluorescence could improve the detection ability of the biosensor in complex biological samples. UCNPs unbound to bacteria could be separated by magnet, improving the sensitivity and detection time of the biosensor.