bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancing Space‐Time Simulation of Random Fields: From Storms to Cyclones and Beyond
Authors: Papalexiou Simon Michael , Serinaldi Francesco , Porcu Emilio
Published: May 2021

Realistic stochastic simulation of hydro‐environmental fluxes in space and time, such as rainfall, is challenging yet of paramount importance to inform environmental risk analysis and decision making under uncertainty. Here, we advance random fields simulation by introducing the concepts of general velocity fields and general anisotropy transformations. This expands the capabilities of the so‐called Complete Stochastic Modeling Solution (CoSMoS) framework enabling the simulation of random fields (RF's) preserving: (a) any non‐Gaussian marginal distribution, (b) any spatiotemporal correlation structure (STCS), (c) general advection expressed by velocity fields with locally varying speed and direction, and (d) locally varying anisotropy. We also introduce new copula‐based STCS's and provide conditions guaranteeing their positive definiteness. To illustrate the potential of CoSMoS, we simulate RF's with complex patterns and motion mimicking rainfall storms moving across an area, spiraling fields resembling weather cyclones, fields converging to (or diverging from) a point, and colliding air masses. The proposed methodology is implemented in the freely available CoSMoS R package.
Rapid Advances in Mobile Mass Spectrometry Enhance Tracer Hydrology and Water Management
Authors: Popp Andrea L. , Manning Cara C. M. , Knapp Julia L. A.
Published: May 2021

Dissolved gases, including noble gases, are versatile environmental tracers. Historically, the application of dissolved (noble) gases as tracers in hydrology used to be limited because their measurement required expensive, laboratory‐based instrumentation operated by highly trained personnel. Here, we highlight recent advances in mobile mass spectrometry (MS) methods for noble and other dissolved gases, which enable low cost, high‐throughput, real‐time measurements. We also present applications using mobile MS to quantify hydrological and biogeochemical processes in groundwater and surface waters and to assess hazards and risks to aquatic environments. Finally, we indicate potential future applications of these instruments to enhance hydrological research.
Predictors of blood pressure response to ultrasound renal denervation in the RADIANCE-HTN SOLO study
Authors: Saxena Manish , Schmieder Roland E. , Kirtane Ajay J. , Mahfoud Felix , Daemen Joost , Basile Jan , Lurz Philipp , Gosse Philippe , Sanghvi Kintur , Fisher Naomi D. L. , Rump Lars C. , Pathak Atul , Blankestijn Peter J. , Mathur Anthony , Wang Yale , Weber Michael A. , Sharp Andrew S. P. , Bloch Michael J. , Barman Neil C. , Claude Lisa , Song Yang , Azizi Michel , Lobo Melvin D.
Published: May 2021

The blood pressure (BP) lowering response to renal denervation (RDN) remains variable with about one-third of patients not responding to ultrasound or radiofrequency RDN. Identification of predictors of the BP response to RDN is needed to optimize patient selection for this therapy. This is a post-hoc analysis of the RADIANCE-HTN SOLO study. BP response to RDN was measured by the change in daytime ambulatory systolic blood pressure (dASBP) at 2 months post procedure. Univariate regression was used initially to assess potential predictors of outcome followed by multivariate regression analysis. In the univariate analysis, predictors of response to RDN were higher baseline daytime ambulatory diastolic blood pressure (dADBP), the use of antihypertensive medications at screening, and presence of orthostatic hypertension (OHTN) whilst the presence of untreated accessory arteries was a negative predictor of response. Multivariate analysis determined that dADBP and use of antihypertensive medications were predictors of response to RDN with a trend for OHTN to predict response. Obese females also appeared to be better responders to RDN in an interaction model. RDN is more effective in patients with elevated baseline dADBP and those with OHTN, suggesting increased peripheral vascular resistance secondary to heightened sympathetic tone. These assessments are easy to perform in clinical setting and may help in phenotyping patients who will respond better to RDN.
Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations
Authors: Greco Raffaella , Alexander Tobias , Burman Joachim , Del Papa Nicoletta , de Vries-Bouwstra Jeska , Farge Dominique , Henes Jörg , Kazmi Majid , Kirgizov Kirill , Muraro Paolo A. , Ricart Elena , Rovira Montserrat , Saccardi Riccardo , Sharrack Basil , Snarski Emilian , Withers Barbara , Jessop Helen , Boglione Claudia , Kramer Ellen , Badoglio Manuela , Labopin Myriam , Orchard Kim , Corbacioglu Selim , Ljungman Per , Mikulska Malgorzata , De la Camara Rafael , Snowden John A. ,   On behalf of the European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP), Infectious Diseases Working Party (IDWP), Pediatric Working Party (PWP), Joint Accreditation Committee of the International Society for Cellular Therapy (ISCT) and EBMT (JACIE), EBMT Nurses Group and Patient Advocacy Committee
Published: May 2021

Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an “endemic” phase and therefore an ongoing risk within a “new normality”. These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice.
Patients with COVID-19: in the dark-NETs of neutrophils
Authors: Ackermann Maximilian , Anders Hans-Joachim , Bilyy Rostyslav , Bowlin Gary L. , Daniel Christoph , De Lorenzo Rebecca , Egeblad Mikala , Henneck Timo , Hidalgo Andrés , Hoffmann Markus , Hohberger Bettina , Kanthi Yogendra , Kaplan Mariana J. , Knight Jason S. , Knopf Jasmin , Kolaczkowska Elzbieta , Kubes Paul , Leppkes Moritz , Mahajan Aparna , Manfredi Angelo A. , Maueröder Christian , Maugeri Norma , Mitroulis Ioannis , Muñoz Luis E. , Narasaraju Teluguakula , Naschberger Elisabeth , Neeli Indira , Ng Lai Guan , Radic Marko Z. , Ritis Konstantinos , Rovere-Querini Patrizia , Schapher Mirco , Schauer Christine , Simon Hans-Uwe , Singh Jeeshan , Skendros Panagiotis , Stark Konstantin , Stürzl Michael , van der Vlag Johan , Vandenabeele Peter , Vitkov Ljubomir , von Köckritz-Blickwede Maren , Yanginlar Cansu , Yousefi Shida , Zarbock Alexander , Schett Georg , Herrmann Martin
Published: May 2021

SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.
Phenotypic homogeneity in childhood epilepsies evolves in gene-specific patterns across 3251 patient-years of clinical data
Authors: Lewis-Smith David , Ganesan Shiva , Galer Peter D. , Helbig Katherine L. , McKeown Sarah E. , O’Brien Margaret , Khankhanian Pouya , Kaufman Michael C. , Gonzalez Alexander K. , Felmeister Alex S. , Krause Roland , Ellis Colin A. , Helbig Ingo
Published: May 2021

While genetic studies of epilepsies can be performed in thousands of individuals, phenotyping remains a manual, non-scalable task. A particular challenge is capturing the evolution of complex phenotypes with age. Here, we present a novel approach, applying phenotypic similarity analysis to a total of 3251 patient-years of longitudinal electronic medical record data from a previously reported cohort of 658 individuals with genetic epilepsies. After mapping clinical data to the Human Phenotype Ontology, we determined the phenotypic similarity of individuals sharing each genetic etiology within each 3-month age interval from birth up to a maximum age of 25 years. 140 of 600 (23%) of all 27 genes and 3-month age intervals with sufficient data for calculation of phenotypic similarity were significantly higher than expect by chance. 11 of 27 genetic etiologies had significant overall phenotypic similarity trajectories. These do not simply reflect strong statistical associations with single phenotypic features but appear to emerge from complex clinical constellations of features that may not be strongly associated individually. As an attempt to reconstruct the cognitive framework of syndrome recognition in clinical practice, longitudinal phenotypic similarity analysis extends the traditional phenotyping approach by utilizing data from electronic medical records at a scale that is far beyond the capabilities of manual phenotyping. Delineation of how the phenotypic homogeneity of genetic epilepsies varies with age could improve the phenotypic classification of these disorders, the accuracy of prognostic counseling, and by providing historical control data, the design and interpretation of precision clinical trials in rare diseases.
Kramers nodal line metals
Authors: Xie Ying-Ming , Gao Xue-Jian , Xu Xiao Yan , Zhang Cheng-Ping , Hu Jin-Xin , Gao Jason Z. , Law K. T.
Published: May 2021

Recently, it was pointed out that all chiral crystals with spin-orbit coupling (SOC) can be Kramers Weyl semimetals (KWSs) which possess Weyl points pinned at time-reversal invariant momenta. In this work, we show that all achiral non-centrosymmetric materials with SOC can be a new class of topological materials, which we term Kramers nodal line metals (KNLMs). In KNLMs, there are doubly degenerate lines, which we call Kramers nodal lines (KNLs), connecting time-reversal invariant momenta. The KNLs create two types of Fermi surfaces, namely, the spindle torus type and the octdong type. Interestingly, all the electrons on octdong Fermi surfaces are described by two-dimensional massless Dirac Hamiltonians. These materials support quantized optical conductance in thin films. We further show that KNLMs can be regarded as parent states of KWSs. Therefore, we conclude that all non-centrosymmetric metals with SOC are topological, as they can be either KWSs or KNLMs.
Non-lithifying microbial ecosystem dissolves peritidal lime sand
Authors: Present Theodore M. , Gomes Maya L. , Trower Elizabeth J. , Stein Nathan T. , Lingappa Usha F. , Naviaux John , Thorpe Michael T. , Cantine Marjorie D. , Fischer Woodward W. , Knoll Andrew H. , Grotzinger John P.
Published: May 2021

Microbialites accrete where environmental conditions and microbial metabolisms promote lithification, commonly through carbonate cementation. On Little Ambergris Cay, Turks and Caicos Islands, microbial mats occur widely in peritidal environments above ooid sand but do not become lithified or preserved. Sediment cores and porewater geochemistry indicated that aerobic respiration and sulfide oxidation inhibit lithification and dissolve calcium carbonate sand despite widespread aragonite precipitation from platform surface waters. Here, we report that in tidally pumped environments, microbial metabolisms can negate the effects of taphonomically-favorable seawater chemistry on carbonate mineral saturation and microbialite development.
PKC-phosphorylation of Liprin-α3 triggers phase separation and controls presynaptic active zone structure
Authors: Emperador-Melero Javier , Wong Man Yan , Wang Shan Shan H. , de Nola Giovanni , Nyitrai Hajnalka , Kirchhausen Tom , Kaeser Pascal S.
Published: May 2021

The active zone of a presynaptic nerve terminal defines sites for neurotransmitter release. Its protein machinery may be organized through liquid–liquid phase separation, a mechanism for the formation of membrane-less subcellular compartments. Here, we show that the active zone protein Liprin-α3 rapidly and reversibly undergoes phase separation in transfected HEK293T cells. Condensate formation is triggered by Liprin-α3 PKC-phosphorylation at serine-760, and RIM and Munc13 are co-recruited into membrane-attached condensates. Phospho-specific antibodies establish phosphorylation of Liprin-α3 serine-760 in transfected cells and mouse brain tissue. In primary hippocampal neurons of newly generated Liprin-α2/α3 double knockout mice, synaptic levels of RIM and Munc13 are reduced and the pool of releasable vesicles is decreased. Re-expression of Liprin-α3 restored these presynaptic defects, while mutating the Liprin-α3 phosphorylation site to abolish phase condensation prevented this rescue. Finally, PKC activation in these neurons acutely increased RIM, Munc13 and neurotransmitter release, which depended on the presence of phosphorylatable Liprin-α3. Our findings indicate that PKC-mediated phosphorylation of Liprin-α3 triggers its phase separation and modulates active zone structure and function.
The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses
Authors: Deng Jun , Chen Qian , Chen Zhian , Liang Kaili , Gao Xin , Wang Xiaohui , Makota Fadzai V. , Ong Hong Sheng , Wan Yanmin , Luo Kaiming , Gong Dongcheng , Yu Xiang , Camuglia Sarina , Zeng Qunxiong , Zhou Tao , Xue Feng , He Jing , Wei Yunbo , Xiao Fan , Ma Jianyang , Hill Danika L. , Pierson Wim , Nguyen Thi H. O. , Zhou Haibo , Wang Yan , Shen Wei , Sun Lingyun , Li Zhanguo , Xia Qiang , Qian Kun , Ye Lilin , Rockman Steven , Linterman Michelle A. , Kedzierska Katherine , Shen Nan , Lu Liwei , Yu Di
Published: May 2021

Follicular helper T (TFH) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate TFH function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying TFH regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human TFH differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs TFH generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of TFH cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure.
Cryo-EM structure of cortical microtubules from human parasite Toxoplasma gondii identifies their microtubule inner proteins
Authors: Wang Xiangli , Fu Yong , Beatty Wandy L. , Ma Meisheng , Brown Alan , Sibley L. David , Zhang Rui
Published: May 2021

In living cells, microtubules (MTs) play pleiotropic roles, which require very different mechanical properties. Unlike the dynamic MTs found in the cytoplasm of metazoan cells, the specialized cortical MTs from Toxoplasma gondii, a prevalent human pathogen, are extraordinarily stable and resistant to detergent and cold treatments. Using single-particle cryo-EM, we determine their ex vivo structure and identify three proteins (TrxL1, TrxL2 and SPM1) as bona fide microtubule inner proteins (MIPs). These three MIPs form a mesh on the luminal surface and simultaneously stabilize the tubulin lattice in both longitudinal and lateral directions. Consistent with previous observations, deletion of the identified MIPs compromises MT stability and integrity under challenges by chemical treatments. We also visualize a small molecule like density at the Taxol-binding site of β-tubulin. Our results provide the structural basis to understand the stability of cortical MTs and suggest an evolutionarily conserved mechanism of MT stabilization from the inside.
The transcriptional landscape of a rewritten bacterial genome reveals control elements and genome design principles
Authors: van Kooten Mariëlle J. F. M. , Scheidegger Clio A. , Christen Matthias , Christen Beat
Published: May 2021

Sequence rewriting enables low-cost genome synthesis and the design of biological systems with orthogonal genetic codes. The error-free, robust rewriting of nucleotide sequences can be achieved with a complete annotation of gene regulatory elements. Here, we compare transcription in Caulobacter crescentus to transcription from plasmid-borne segments of the synthesized genome of C. ethensis 2.0. This rewritten derivative contains an extensive amount of supposedly neutral mutations, including 123’562 synonymous codon changes. The transcriptional landscape refines 60 promoter annotations, exposes 18 termination elements and links extensive transcription throughout the synthesized genome to the unintentional introduction of sigma factor binding motifs. We reveal translational regulation for 20 CDS and uncover an essential translational regulatory element for the expression of ribosomal protein RplS. The annotation of gene regulatory elements allowed us to formulate design principles that improve design schemes for synthesized DNA, en route to a bright future of iteration-free programming of biological systems.
All-dielectric chiral-field-enhanced Raman optical activity
Authors: Xiao Ting-Hui , Cheng Zhenzhou , Luo Zhenyi , Isozaki Akihiro , Hiramatsu Kotaro , Itoh Tamitake , Nomura Masahiro , Iwamoto Satoshi , Goda Keisuke
Published: May 2021

Raman optical activity (ROA) is effective for studying the conformational structure and behavior of chiral molecules in aqueous solutions and is advantageous over X-ray crystallography and nuclear magnetic resonance spectroscopy in sample preparation and cost performance. However, ROA signals are inherently minuscule; 3–5 orders of magnitude weaker than spontaneous Raman scattering due to the weak chiral light–matter interaction. Localized surface plasmon resonance on metallic nanoparticles has been employed to enhance ROA signals, but suffers from detrimental spectral artifacts due to its photothermal heat generation and inability to efficiently transfer and enhance optical chirality from the far field to the near field. Here we demonstrate all-dielectric chiral-field-enhanced ROA by devising a silicon nanodisk array and exploiting its dark mode to overcome these limitations. Specifically, we use it with pairs of chemical and biological enantiomers to show >100x enhanced chiral light–molecule interaction with negligible artifacts for ROA measurements.
Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics
Authors: Ding Ren-Bo , Chen Ping , Rajendran Barani Kumar , Lyu Xueying , Wang Haitao , Bao Jiaolin , Zeng Jianming , Hao Wenhui , Sun Heng , Wong Ada Hang-Heng , Valecha Monica Vishnu , Yang Eun Ju , Su Sek Man , Choi Tak Kan , Liu Shuiming , Chan Kin Iong , Yang Ling-Lin , Wu Jingbo , Miao Kai , Chen Qiang , Shim Joong Sup , Xu Xiaoling , Deng Chu-Xia
Published: May 2021

Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer type with high morbidity in Southeast Asia, however the pathogenic mechanism of this disease is poorly understood. Using integrative pharmacogenomics, we find that NPC subtypes maintain distinct molecular features, drug responsiveness, and graded radiation sensitivity. The epithelial carcinoma (EC) subtype is characterized by activations of microtubule polymerization and defective mitotic spindle checkpoint related genes, whereas sarcomatoid carcinoma (SC) and mixed sarcomatoid-epithelial carcinoma (MSEC) subtypes exhibit enriched epithelial-mesenchymal transition (EMT) and invasion promoting genes, which are well correlated with their morphological features. Furthermore, patient-derived organoid (PDO)-based drug test identifies potential subtype-specific treatment regimens, in that SC and MSEC subtypes are sensitive to microtubule inhibitors, whereas EC subtype is more responsive to EGFR inhibitors, which is synergistically enhanced by combining with radiotherapy. Through combinational chemoradiotherapy (CRT) screening, effective CRT regimens are also suggested for patients showing less sensitivity to radiation. Altogether, our study provides an example of applying integrative pharmacogenomics to establish a personalized precision oncology for NPC subtype-guided therapies.
Sensitivity, specificity, and accuracy of a liquid biopsy approach utilizing molecular amplification pools
Authors: Garcia Jessica , Kamps-Hughes Nick , Geiguer Florence , Couraud Sébastien , Sarver Brice , Payen Léa , Ionescu-Zanetti Cristian
Published: May 2021

Circulating cell-free DNA (cfDNA) has the potential to be a specific biomarker for the therapeutic management of lung cancer patients. Here, a new sequencing error-reduction method based on molecular amplification pools (MAPs) was utilized to analyze cfDNA in lung cancer patients. We determined the accuracy of MAPs plasma sequencing with respect to droplet digital polymerase chain reaction assays (ddPCR), and tested whether actionable mutation discovery is improved by next-generation sequencing (NGS) in a clinical setting. This study reports data from 356 lung cancer patients receiving plasma testing as part of routine clinical management. Sequencing of cfDNA via MAPs had a sensitivity of 98.5% and specificity 98.9%. The ddPCR assay was used as the reference, since it is an established, accurate assay that can be performed contemporaneously on the same plasma sample. MAPs sequencing detected somatic variants in 261 of 356 samples (73%). Non-actionable clonal hematopoiesis-associated variants were identified via sequencing in 21% of samples. The accuracy of this cfDNA sequencing approach was similar to that of ddPCR assays in a clinical setting, down to an allele frequency of 0.1%. Due to broader coverage and high sensitivity for insertions and deletions, sequencing via MAPs afforded important detection of additional actionable mutations.
Power determination in vitamin D randomised control trials and characterising factors affecting it through a novel simulation-based tool
Authors: Wyse Jason , Mangan Rebecca , Zgaga Lina
Published: May 2021

Thousands of observational studies have linked vitamin D deficiency with numerous diseases, but randomised controlled trials (RCTs) often fail to show benefit of supplementation. Population characteristics and trial design have long been suspected to undermine power but were not systematically investigated. We propose a flexible generative model to characterise benefit of vitamin D supplementation at the individual level, and use this to quantify power in RCTs. The model can account for seasonality and population heterogeneity. In a simulated 1-year trial with 1000 participants per arm and assuming a 25-hydroxyvitamin D (25OHD) increase of 20 nmol/L due to the intervention, with baseline 25OHD in the population of 15, 35, 50, 60 and 75 nmol/L, the power to detect intervention effect was 77%, 99%, 95%, 68% and 19%, respectively. The number of participants required per arm to achieve 80% power according to baseline 25OHD of 15–60 nmol/L was 1200, 400, 600 and 1400, respectively. As expected, larger increases in 25OHD due to supplementation improved power in certain scenarios. For a population baseline of 50 nmol/L, with 1500 participants in each arm, there was 100% power to detect a 20 nmol/L 25OHD increase while it was 76% for a 10 nmol/L increase. Population characteristics and trial design, including temporal considerations, have a dramatic impact on power and required sample size in vitamin D RCTs.
Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p
Authors: Barbier Roberto H. , McCrea Edel M. , Lee Kristi Y. , Strope Jonathan D. , Risdon Emily N. , Price Douglas K. , Chau Cindy H. , Figg William D.
Published: May 2021

Understanding mechanisms of resistance to abiraterone, one of the primary drugs approved for the treatment of castration resistant prostate cancer, remains a priority. The organic anion polypeptide 1B3 (OATP1B3, encoded by SLCO1B3) transporter has been shown to transport androgens into prostate cancer cells. In this study we observed and investigated the mechanism of induction of SLCO1B3 by abiraterone. Prostate cancer cells (22Rv1, LNCaP, and VCAP) were treated with anti-androgens and assessed for SLCO1B3 expression by qPCR analysis. Abiraterone treatment increased SLCO1B3 expression in 22Rv1 cells in vitro and in the 22Rv1 xenograft model in vivo. MicroRNA profiling of abiraterone-treated 22Rv1 cells was performed using a NanoString nCounter miRNA panel followed by miRNA target prediction. TargetScan and miRanda prediction tools identified hsa-miR-579-3p as binding to the 3′-untranslated region (3′UTR) of the SLCO1B3. Using dual luciferase reporter assays, we verified that hsa-miR-579-3p indeed binds to the SLCO1B3 3′UTR and significantly inhibited SLCO1B3 reporter activity. Treatment with abiraterone significantly downregulated hsa-miR-579-3p, indicating its potential role in upregulating SLCO1B3 expression. In this study, we demonstrated a novel miRNA-mediated mechanism of abiraterone-induced SLCO1B3 expression, a transporter that is also responsible for driving androgen deprivation therapy resistance. Understanding mechanisms of abiraterone resistance mediated via differential miRNA expression will assist in the identification of potential miRNA biomarkers of treatment resistance and the development of future therapeutics.
An in-depth analysis of the mitochondrial phylogenetic landscape of Cambodia
Authors: Kloss-Brandstätter Anita , Summerer Monika , Horst David , Horst Basil , Streiter Gertraud , Raschenberger Julia , Kronenberg Florian , Sanguansermsri Torpong , Horst Jürgen , Weissensteiner Hansi
Published: May 2021

Cambodia harbours a variety of human aboriginal populations that have scarcely been studied in terms of genetic diversity of entire mitochondrial genomes. Here we present the matrilineal gene pool of 299 Cambodian refugees from three different ethnic groups (Cham, Khmer, and Khmer Loeu) deriving from 16 Cambodian districts. After establishing a DNA-saving high-throughput strategy for mitochondrial whole-genome Sanger sequencing, a HaploGrep based workflow was used for quality control, haplogroup classification and phylogenetic reconstruction. The application of diverse phylogenetic algorithms revealed an exciting picture of the genetic diversity of Cambodia, especially in relation to populations from Southeast Asia and from the whole world. A total of 224 unique haplotypes were identified, which were mostly classified under haplogroups B5a1, F1a1, or categorized as newly defined basal haplogroups or basal sub-branches of R, N and M clades. The presence of autochthonous maternal lineages could be confirmed as reported in previous studies. The exceptional homogeneity observed between and within the three investigated Cambodian ethnic groups indicates genetic isolation of the whole population. Between ethnicities, genetic barriers were not detected. The mtDNA data presented here increases the phylogenetic resolution in Cambodia significantly, thereby highlighting the need for an update of the current human mtDNA phylogeny.
Berezinskii–Kosterlitz–Thouless phase induced by dissipating quasisolitons
Authors: Gawryluk Krzysztof , Brewczyk Mirosław
Published: May 2021

We theoretically study the sound propagation in a two-dimensional weakly interacting uniform Bose gas. Using the classical fields approximation we analyze in detail the properties of density waves generated both in a weak and strong perturbation regimes. While in the former case density excitations can be described in terms of hydrodynamic or collisionless sound, the strong disturbance of the system results in a qualitatively different response. We identify observed structures as quasisolitons and uncover their internal complexity for strong perturbation case. For this regime quasisolitons break into vortex pairs as time progresses, eventually reaching an equilibrium state. We find this state, characterized by only fluctuating in time averaged number of pairs of opposite charge vortices and by appearance of a quasi-long-range order, as the Berezinskii–Kosterlitz–Thouless (BKT) phase.
Agreement between laboratory-based and non-laboratory-based Framingham risk score in Southern Iran
Authors: Rezaei Fatemeh , Seif Mozhgan , Gandomkar Abdullah , Fattahi Mohammad Reza , Hasanzadeh Jafar
Published: May 2021

The Framingham 10-year cardiovascular disease risk is measured by laboratory-based and non-laboratory-based models. This study aimed to determine the agreement between these two models in a large population in Southern Iran. In this study, the baseline data of 8138 individuals participated in the Pars cohort study were used. The participants had no history of cardiovascular disease or stroke. For the laboratory-based risk model, scores were determined based on age, sex, current smoking, diabetes, systolic blood pressure (SBP) and treatment status, total cholesterol, and High-Density Lipoprotein. For the non-laboratory-based risk model, scores were determined based on age, sex, current smoking, diabetes, SBP and treatment status, and Body Mass Index. The agreement between these two models was determined by Bland Altman plots for agreement between the scores and kappa statistic for agreement across the risk groups. Bland Altman plots showed that the limits of agreement were reasonable for females < 60 years old (95% CI: −2.27–4.61%), but of concern for those ≥ 60 years old (95% CI: −3.45–9.67%), males < 60 years old (95% CI: −2.05–8.91%), and males ≥ 60 years old (95% CI: −3.01–15.23%). The limits of agreement were wider for males ≥ 60 years old in comparison to other age groups. According to the risk groups, the agreement was better in females than in males, which was moderate for females < 60 years old (kappa = 0.57) and those ≥ 60 years old (kappa = 0.51). The agreement was fair for the males < 60 years old (kappa = 0.39) and slight for those ≥ 60 years old (Kappa = 0.14). The results showed that in overall participants, the agreement between the two risk scores was moderate according to risk grouping. Therefore, our results suggest that the non-laboratory-based risk model can be used in resource-limited settings where individuals cannot afford laboratory tests and extensive laboratories are not available.
Fetal movement counting is associated with the reduction of delayed maternal reaction after perceiving decreased fetal movements: a prospective study
Authors: Koshida Shigeki , Tokoro Shinsuke , Katsura Daisuke , Tsuji Shunichiro , Murakami Takashi , Takahashi Kentaro
Published: May 2021

Maternal perception of decreased fetal movement is associated with adverse perinatal outcomes. Although there have been several studies on interventions related to the fetal movements count, most focused on adverse perinatal outcomes, and little is known about the impact of the fetal movement count on maternal behavior after the perception of decreased fetal movement. We investigated the impact of the daily fetal movement count on maternal behavior after the perception of decreased fetal movement and on the stillbirth rate in this prospective population-based study. Pregnant women in Shiga prefecture of Japan were asked to count the time of 10 fetal movements from 34 weeks of gestation. We analyzed 101 stillbirths after the intervention compared to 121 stillbirths before the intervention. In multivariable analysis, maternal delayed visit to a health care provider after the perception of decreased fetal movement significantly reduced after the intervention (aOR 0.31, 95% CI 0.11–0.83). Our regional stillbirth rates in the pre-intervention and post-intervention periods were 3.06 and 2.70 per 1000 births, respectively. Informing pregnant women about the fetal movement count was associated with a reduction in delayed maternal reaction after the perception of decreased fetal movement, which might reduce stillbirths.
COVID-19 diagnosis by routine blood tests using machine learning
Authors: Kukar Matjaž , Gunčar Gregor , Vovko Tomaž , Podnar Simon , Černelč Peter , Brvar Miran , Zalaznik Mateja , Notar Mateja , Moškon Sašo , Notar Marko
Published: May 2021

Physicians taking care of patients with COVID-19 have described different changes in routine blood parameters. However, these changes hinder them from performing COVID-19 diagnoses. We constructed a machine learning model for COVID-19 diagnosis that was based and cross-validated on the routine blood tests of 5333 patients with various bacterial and viral infections, and 160 COVID-19-positive patients. We selected the operational ROC point at a sensitivity of 81.9% and a specificity of 97.9%. The cross-validated AUC was 0.97. The five most useful routine blood parameters for COVID-19 diagnosis according to the feature importance scoring of the XGBoost algorithm were: MCHC, eosinophil count, albumin, INR, and prothrombin activity percentage. t-SNE visualization showed that the blood parameters of the patients with a severe COVID-19 course are more like the parameters of a bacterial than a viral infection. The reported diagnostic accuracy is at least comparable and probably complementary to RT-PCR and chest CT studies. Patients with fever, cough, myalgia, and other symptoms can now have initial routine blood tests assessed by our diagnostic tool. All patients with a positive COVID-19 prediction would then undergo standard RT-PCR studies to confirm the diagnosis. We believe that our results represent a significant contribution to improvements in COVID-19 diagnosis.
Novel assessment of the variation in cervical inter-vertebral motor control in a healthy pain-free population
Authors: Lindstrøm René , Breen Alexander , Qu Ning , du Rose Alister , Andersen Victoria Blogg , Breen Alan
Published: May 2021

Spinal control at intervertebral levels is dependent on interactions between the active, passive and neural control elements. However, this has never been quantifiable, and has therefore been outside the reach of clinical assessments and research. This study used fluoroscopy during repeated unconstrained flexion and return neck movements to calculate intersegmental motor control (MC), defined as the difference and variation in repeated continuous angular motion from its average path. The study aimed to determine control values for MC at individual levels and its variability. Twenty male volunteers aged 19–29 received fluoroscopic screening of their cervical spines during 4 repetitions of neutral to full flexion and return motion. Moving vertebral images from C0–C1 to C6–C7 were tracked using cross-correlation codes written in Matlab. MC for each level was defined as the mean of the absolute differences between each repetition’s angular path and their mean and its variability as represented by the SD. 1-way ANOVA and Tukey multiple comparisons were used to identify significant contrasts between levels. The mean MC differences and SDs were highest at C1-2, suggesting that this level has the least control and the most variability. Results at this level alone were highly significant (F-ratio 10.88 and 9.79 P < 0.0001). Significant contrasts were only found between C1-C2 and all other levels. The mean MC difference for summed C1-6 levels was 3.4° (0.7–6.1). This study is the first to quantify intervertebral MC in the cervical spine in asymptomatic people. Studies of neck pain patients are now merited.
Genome-wide SNPs redefines species boundaries and conservation units in the freshwater mussel genus Cyprogenia of North America
Authors: Kim Kyung Seok , Roe Kevin J.
Published: May 2021

Detailed information on species delineation and population genetic structure is a prerequisite for designing effective restoration and conservation strategies for imperiled organisms. Phylogenomic and population genomic analyses based on genome-wide double digest restriction-site associated DNA sequencing (ddRAD-Seq) data has identified three allopatric lineages in the North American freshwater mussel genusCyprogenia.Cyprogenia stegariais restricted to the Eastern Highlands and displays little genetic structuring within this region. However, two allopatric lineages ofC. abertiin the Ozark and Ouachita highlands exhibit substantial levels (mean uncorrectedFST = 0.368) of genetic differentiation and each warrants recognition as a distinct evolutionary lineage. Lineages ofCyprogeniain the Ouachita and Ozark highlands are further subdivided reflecting structuring at the level of river systems. Species tree inference and species delimitation in a Bayesian framework using single nucleotide polymorphisms (SNP) data supported results from phylogenetic analyses, and supports three species ofCyprogeniaover the currently recognized two species. A comparison of SNPs generated from both destructively and non-destructively collected samples revealed no significant difference in the SNP error rate, quality and amount of ddRAD sequence reads, indicating that nondestructive or trace samples can be effectively utilized to generate SNP data for organisms for which destructive sampling is not permitted.
Integrative nomogram of intratumoral, peritumoral, and lymph node radiomic features for prediction of lymph node metastasis in cT1N0M0 lung adenocarcinomas
Authors: Das Sushant Kumar , Fang Ke-Wei , Xu Long , Li Bing , Zhang Xin , Yang Han-Feng
Published: May 2021

Radiomics studies to predict lymph node (LN) metastasis has only focused on either primary tumor or LN alone. However, combining radiomics features from multiple sources may reflect multiple characteristic of the lesion thereby increasing the discriminative performance of the radiomic model. Therefore, the present study intends to evaluate the efficiency of integrative nomogram, created by combining clinical parameters and radiomics features extracted from gross tumor volume (GTV), peritumoral volume (PTV) and LN, for the preoperative prediction of LN metastasis in clinical cT1N0M0 adenocarcinoma. A primary cohort of 163 patients (training cohort, 113; and internal validation cohort, 50) and an external validation cohort of 53 patients with clinical stage cT1N0M0 were retrospectively included. Features were extracted from three regions of interests (ROIs): GTV; PTV (5.0 mm around the tumor) and LN on pre-operative contrast enhanced computed tomography (CT). LASSO logistic regression method was used to build radiomic signatures. Multivariable regression analysis was used to build a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. The discriminative performance of nomogram was validated both internally and externally. The radiomic signatures using the features of GTV, PTV and LN showed a good ability in predicting LN metastasis with an area under the curve (AUC) of 0.74 (95% CI 0.60–0.88), 0.72 (95% CI 0.57–0.87) and 0.64 (95% CI 0.48–0.80) respectively in external validation cohort. The integration of different signature together further increases the discriminatory ability: GTV + PTV (GPTV): AUC 0.75 (95% CI 0.61–0.89) and GPTV + LN: AUC 0.76 (95% CI 0.61–0.91) in external validation cohort. An integrative nomogram of clinical parameters and radiomic features demonstrated further increase in discriminatory ability with AUC of 0.79 (95% CI 0.66–0.93) in external validation cohort. The nomogram showed good calibration. Decision curve analysis demonstrated that the radiomic nomogram was clinically useful. The integration of information from clinical parameters along with CT radiomics information from GTV, PTV and LN was feasible and increases the predictive performance of the nomogram in predicting LN status in cT1N0M0 adenocarcinoma patients suggesting merit of information integration from multiple sources in building prediction model.
Remote ischemic preconditioning improves tissue oxygenation in a porcine model of controlled hemorrhage without fluid resuscitation
Authors: Yaniv Gal , Eisenkraft Arik , Gavish Lilach , Wagnert-Avraham Linn , Nachman Dean , Megreli Jacob , Shimon Gil , Rimbrot Daniel , Simon Ben , Berman Asaf , Cohen Matan , Kushnir David , Shaylor Ruth , Batzofin Baruch , Firman Shimon , Shlaifer Amir , Hartal Michael , Heled Yuval , Glassberg Elon , Kreiss Yitshak , Gertz S. David
Published: May 2021

Remote ischemic preconditioning (RIPC) involves deliberate, brief interruptions of blood flow to increase the tolerance of distant critical organs to ischemia. This study tests the effects of limb RIPC in a porcine model of controlled hemorrhage without replacement therapy simulating an extreme field situation of delayed evacuation to definitive care. Twenty-eight pigs (47 ± 6 kg) were assigned to: (1) control, no procedure (n = 7); (2) HS = hemorrhagic shock (n = 13); and (3) RIPC + HS = remote ischemic preconditioning followed by hemorrhage (n = 8). The animals were observed for 7 h after bleeding without fluid replacement. Survival rate between animals of the RIPC + HS group and those of the HS group were similar (HS, 6 of 13[46%]-vs-RIPC + HS, 4 of 8[50%], p = 0.86 by Chi-square). Animals of the RIPC + HS group had faster recovery of mean arterial pressure and developed higher heart rates without complications. They also had less decrease in pH and bicarbonate, and the increase in lactate began later. Global oxygen delivery was higher, and tissue oxygen extraction ratio lower, in RIPC + HS animals. These improvements after RIPC in hemodynamic and metabolic status provide essential substrates for improved cellular response after hemorrhage and reduction of the likelihood of potentially catastrophic consequences of the accompanying ischemia.
Leader peptide exchange to produce hybrid, new-to-nature ribosomal natural products
Authors: Franz Laura , Koehnke Jesko
Published: May 2021

We present a Sortase A-based approach to synthesise new-to-nature hybrid RiPPs modified using RiPP enzymes from unrelated pathways.
Ratiometric sensing of Zn2+ with a new benzothiazole-based fluorescent sensor and living cell imaging
Authors: Wu Qi , Feng LiHeng , Chao Jian Bin , Wang Yu , Shuang Shaomin
Published: May 2021

A new fluorescent probe, 3-(benzo[d]thiazol-2-yl)-5-bromosalicylaldehyde-4N-phenyl thiosemicarbazone (BTT), for ratiometric sensing of Zn2+ ions in methanol/HEPES buffer solution (3 : 2, pH = 7.4) is reported in this paper.
3D printed imaging platform for portable cell counting
Authors: Awate Diwakar M. , Pola Cicero C. , Shumaker Erica , Gomes Carmen L. , Juárez Jaime J.
Published: May 2021

3D printing of optomechanical components can expand the application of point-of-care (POC) diagnostics to resource-limited environments.
Large-scale investigation of single cell activities and response dynamics in a microarray chip with a microfluidics-fabricated microporous membrane
Authors: Han Kai , Sun Meilin , Zhang Jinwei , Fu Wenzhu , Hu Rui , Liu Dan , Liu Wenming
Published: May 2021

We present a parallel, large-scale, and versatile investigation of the single cell activity and response dynamics in a facile assembled microwell array chip with a microfluidics-molded microporous membrane.
An asymmetric Schiff base-functionalized gold nanoparticle-based colorimetric sensor for Hg2+ ion determination: experimental and DFT studies
Authors: Amourizi Fereshteh , Dashtian Kheibar , Ghaedi Mehrorang , Hosseinzadeh Behzad
Published: May 2021

Polyvinyl alcohol-capped citrate-stabilized gold nanoparticles, functionalized with newly synthesized Schiff base derived from 3,4-diaminotoluene and benzaldehyde, to determine Hg2+ ions with HOMO–LUMO orbital study.
Specific enrichment and glycosylation discrepancy profiling of cellular exosomes using a dual-affinity probe
Authors: Zhang Ning , Hu Xufang , Chen Haolin , Deng Chunhui , Sun Nianrong
Published: May 2021

Fe3O4@TiO2-GSH is applied to enrich cell-derived exosomes and exosomal glycopeptides consecutively to analyze their glycosylation discrepancy.
Three-component reaction of gem-difluorinated cyclopropanes with alkenes and B2pin2 for the synthesis of monofluoroalkenes
Authors: Suliman Ayman M. Y. , Ahmed Ebrahim-Alkhalil M. A. , Gong Tian-Jun , Fu Yao
Published: May 2021

Cu/Pd-Catalyzed borylfluoroallylation of alkenes with gem-difluorinated cyclopropanes and B2pin2 was achieved, providing a modular and general strategy for the synthesis of monofluoroalkenes.
Assembling gold nanobipyramids into chiral plasmonic nanostructures with DNA origami
Authors: Dong Jinyi , Zhou Yihao , Pan Jiahao , Zhou Chao , Wang Qiangbin
Published: May 2021

Chiral AuBNP dimer nanostructures with stronger CD signals than AuNR dimers.
Zn(ii) and Cd(ii) coordination polymers with a new angular bis-pyridyl-bis-amide: synthesis, structures and sensing properties
Authors: Yang Xiang-Kai , Lee Wei-Te , Hu Ji-Hong , Chen Jhy-Der
Published: May 2021

Zn(ii) and Cd(ii) coordination polymers that show a 2D double layer with the rare (46·64)-5 L4 topology and a 3D framework with a new (4·5·6)(45·55·69·7·8) topology, respectively, show good selectivity toward the detection of Fe3+ ions.
A coarse-grained xDLVO model for colloidal protein–protein interactions
Authors: Pusara Srdjan , Yamin Peyman , Wenzel Wolfgang , Krstić Marjan , Kozlowska Mariana
Published: May 2021

Shape-based coarse graining of proteins permits anisotropic intermolecular interactions modulating protein solubility. Together with the ion–protein dispersion, it allows the calculation of theB22coefficients without experimental fitting.
Role of ultramicropores in the remarkable gas storage in hypercrosslinked polystyrene networks studied by positron annihilation
Authors: Li Yilin , Liu Junjie , Kong Jingjing , Qi Ning , Chen Zhiquan
Published: May 2021

In this paper, hypercrosslinked polystyrene (HCLPS) networks were synthesized by radical bulk polymerization and Friedel–Crafts alkylation reactions using vinylbenzyl-co-divinylbenzene chloride (VBC-DVB) as the precursors.
Construction of a novel mechanoluminescent phosphor Li2MgGeO4:xMn2+ by defect control
Authors: Bai Yuxing , Zheng Zhongzhong , Wu Li , Kong Yongfa , Zhang Yi , Xu Jingjun
Published: May 2021

The intrinsic defects modulated by cationic substitution enable the construction of a novel mechanoluminescent material.
Correction: An oxygen-blocking oriented multifunctional solid–electrolyte interphase as a protective layer for a lithium metal anode in lithium–oxygen batteries
Authors: Lin Xiao-Dong , Gu Yu , Shen Xiao-Ru , Wang Wei-Wei , Hong Yu-Hao , Wu Qi-Hui , Zhou Zhi-You , Wu De-Yin , Chang Jeng-Kuei , Zheng Ming-Sen , Mao Bing-Wei , Dong Quan-Feng
Published: May 2021

Correction for ‘An oxygen-blocking oriented multifunctional solid–electrolyte interphase as a protective layer for a lithium metal anode in lithium–oxygen batteries’ by Xiao-Dong Lin et al., Energy Environ. Sci., 2021, 14, 1439–1448, DOI: 10.1039/D0EE02931A.