bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudogene ACTBP2 increases blood–brain barrier permeability by promoting KHDRBS2 transcription through recruitment of KMT2D/WDR5 in Aβ1–42 microenvironment
Authors: Liu Qianshuo , Liu Xiaobai , Zhao Defeng , Ruan Xuelei , Su Rui , Shang Xiuli , Wang Di , Yang Chunqing , Xue Yixue
Published: June 2021

The blood–brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer’s disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. We elucidated the function and possible molecular mechanisms of the effect of pseudogene ACTBP2 on the permeability of BBB in Aβ1–42 microenvironment. BBB model treated with Aβ1–42 for 48 h were used to simulate Aβ-mediated BBB dysfunction in AD. We proved that pseudogene ACTBP2, RNA-binding protein KHDRBS2, and transcription factor HEY2 are highly expressed in ECs that were obtained in a BBB model in vitro in Aβ1–42 microenvironment. In Aβ1–42-incubated ECs, ACTBP2 recruits methyltransferases KMT2D and WDR5, binds to KHDRBS2 promoter, and promotes KHDRBS2 transcription. The interaction of KHDRBS2 with the 3′UTR of HEY2 mRNA increases the stability of HEY2 and promotes its expression. HEY2 increases BBB permeability in Aβ1–42 microenvironment by transcriptionally inhibiting the expression of ZO-1, occludin, and claudin-5. We confirmed that knocking down of Khdrbs2 or Hey2 increased the expression levels of ZO-1, occludin, and claudin-5 in APP/PS1 mice brain microvessels. ACTBP2/KHDRBS2/HEY2 axis has a crucial role in the regulation of BBB permeability in Aβ1–42 microenvironment, which may provide a novel target for the therapy of AD.
Revisiting steroidogenesis and its role in immune regulation with the advanced tools and technologies
Authors: Chakraborty Soura , Pramanik Jhuma , Mahata Bidesh
Published: June 2021

Historically tools and technologies facilitated scientific discoveries. Steroid hormone research is not an exception. Unfortunately, the dramatic advancement of the field faded this research area and flagged it as a solved topic. However, it should have been the opposite. The area should glitter with its strong foundation and attract next-generation scientists. Over the past century, a myriad of new facts on biochemistry, molecular biology, cell biology, physiology and pathology of the steroid hormones was discovered. Several innovations were made and translated into life-saving treatment strategies such as synthetic steroids, and inhibitors of steroidogenesis and steroid signaling. Steroid molecules exhibit their diverse effects on cell metabolism, salt and water balance, development and function of the reproductive system, pregnancy, and immune-cell function. Despite vigorous research, the molecular basis of the immunomodulatory effect of steroids is still mysterious. The recent excitement on local extra-glandular steroidogenesis in regulating inflammation and immunity is revitalizing the topic with a new perspective. Therefore, here we review the role of steroidogenesis in regulating inflammation and immunity, discuss the unresolved questions, and how this area can bring another golden age of steroid hormone research with the development of new tools and technologies and advancement of the scientific methods.
Multiple fermion scattering in the weakly coupled spin-chain compound YbAlO3
Authors: Nikitin S. E. , Nishimoto S. , Fan Y. , Wu J. , Wu L. S. , Sukhanov A. S. , Brando M. , Pavlovskii N. S. , Xu J. , Vasylechko L. , Yu R. , Podlesnyak A.
Published: June 2021

The Heisenberg antiferromagnetic spin-1/2 chain, originally introduced almost a century ago, is one of the best studied models in quantum mechanics due to its exact solution, but nevertheless it continues to present new discoveries. Its low-energy physics is described by the Tomonaga-Luttinger liquid of spinless fermions, similar to the conduction electrons in one-dimensional metals. In this work we investigate the Heisenberg spin-chain compound YbAlO3 and show that the weak interchain coupling causes Umklapp scattering between the left- and right-moving fermions and stabilizes an incommensurate spin-density wave order at q = 2kF under finite magnetic fields. These Umklapp processes open a route to multiple coherent scattering of fermions, which results in the formation of satellites at integer multiples of the incommensurate fundamental wavevector Q = nq. Our work provides surprising and profound insight into bandstructure control for emergent fermions in quantum materials, and shows how neutron diffraction can be applied to investigate the phenomenon of coherent multiple scattering in metals through the proxy of quantum magnetic systems.
Distinct mechanisms of the human mitoribosome recycling and antibiotic resistance
Authors: Koripella Ravi Kiran , Deep Ayush , Agrawal Ekansh K. , Keshavan Pooja , Banavali Nilesh K. , Agrawal Rajendra K.
Published: June 2021

Ribosomes are recycled for a new round of translation initiation by dissociation of ribosomal subunits, messenger RNA and transfer RNA from their translational post-termination complex. Here we present cryo-EM structures of the human 55S mitochondrial ribosome (mitoribosome) and the mitoribosomal large 39S subunit in complex with mitoribosome recycling factor (RRFmt) and a recycling-specific homolog of elongation factor G (EF-G2mt). These structures clarify an unusual role of a mitochondria-specific segment of RRFmt, identify the structural distinctions that confer functional specificity to EF-G2mt, and show that the deacylated tRNA remains with the dissociated 39S subunit, suggesting a distinct sequence of events in mitoribosome recycling. Furthermore, biochemical and structural analyses reveal that the molecular mechanism of antibiotic fusidic acid resistance for EF-G2mt is markedly different from that of mitochondrial elongation factor EF-G1mt, suggesting that the two human EF-Gmts have evolved diversely to negate the effect of a bacterial antibiotic.
Pixelated bifunctional metasurface-driven dynamic vectorial holographic color prints for photonic security platform
Authors: Kim Inki , Jang Jaehyuck , Kim Gyeongtae , Lee Jihae , Badloe Trevon , Mun Jungho , Rho Junsuk
Published: June 2021

Vectorial holography has gained a lot of attention due to the promise of versatile polarization control of structured light for enhanced optical security and multi-channel optical communication. Here, we propose a bifunctional metasurface which combines both structural color printing and vectorial holography with eight polarization channels towards advanced encryption applications. The structural colour prints are observed under white light while the polarization encoded holograms are reconstructed under laser illumination. To encode multiple holographic images for different polarization states, a pixelated metasurface is adopted. As a proof-of-concept, we devise an electrically tunable optical security platform incorporated with liquid crystals. The optical security platform is doubly encrypted: an image under white light is decrypted to provide the first key and the corresponding information is used to fully unlock the encrypted information via projected vectorial holographic images. Such an electrically tunable optical security platform may enable smart labels for security and anticounterfeiting applications.
P32-specific CAR T cells with dual antitumor and antiangiogenic therapeutic potential in gliomas
Authors: Rousso-Noori Liat , Mastandrea Ignacio , Talmor Shauli , Waks Tova , Globerson Levin Anat , Haugas Maarja , Teesalu Tambet , Alvarez-Vallina Luis , Eshhar Zelig , Friedmann-Morvinski Dinorah
Published: June 2021

Glioblastoma is considered one of the most aggressive malignancies in adult and pediatric patients. Despite decades of research no curative treatment is available and it thus remains associated with a very dismal prognosis. Although recent pre-clinical and clinical studies have demonstrated the feasibility of chimeric antigen receptors (CAR) T cell immunotherapeutic approach in glioblastoma, tumor heterogeneity and antigen loss remain among one of the most important challenges to be addressed. In this study, we identify p32/gC1qR/HABP/C1qBP to be specifically expressed on the surface of glioma cells, making it a suitable tumor associated antigen for redirected CAR T cell therapy. We generate p32 CAR T cells and find them to recognize and specifically eliminate p32 expressing glioma cells and tumor derived endothelial cells in vitro and to control tumor growth in orthotopic syngeneic and xenograft mouse models. Thus, p32 CAR T cells may serve as a therapeutic option for glioblastoma patients.
Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma
Authors: Raita Yoshihiko , Pérez-Losada Marcos , Freishtat Robert J. , Harmon Brennan , Mansbach Jonathan M. , Piedra Pedro A. , Zhu Zhaozhong , Camargo Carlos A. , Hasegawa Kohei
Published: June 2021

Respiratory syncytial virus (RSV) bronchiolitis is not only the leading cause of hospitalization in U.S. infants, but also a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically-distinct endotypes. Here, we integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicentre prospective cohort study. We identified four biologically- and clinically-meaningful endotypes: A) clinicalclassicmicrobiomeM. nonliquefaciensinflammationIFN-intermediate, B) clinicalatopicmicrobiomeS. pneumoniae/M. catarrhalisinflammationIFN-high, C) clinicalseveremicrobiomemixedinflammationIFN-low, and D) clinicalnon-atopicmicrobiomeM.catarrhalisinflammationIL-6. Particularly, compared with endotype A infants, endotype B infants—who are characterized by a high proportion of IgE sensitization and rhinovirus coinfection,S. pneumoniae/M. catarrhaliscodominance, and high IFN-α and -γ response—had a significantly higher risk for developing asthma (9% vs. 38%; OR, 6.00: 95%CI, 2.08–21.9; P = 0.002). Our findings provide an evidence base for the early identification of high-risk children during a critical period of airway development.
Direct observation of trap-assisted recombination in organic photovoltaic devices
Authors: Zeiske Stefan , Sandberg Oskar J. , Zarrabi Nasim , Li Wei , Meredith Paul , Armin Ardalan
Published: June 2021

Trap-assisted recombination caused by localised sub-gap states is one of the most important first-order loss mechanism limiting the power-conversion efficiency of all solar cells. The presence and relevance of trap-assisted recombination in organic photovoltaic devices is still a matter of some considerable ambiguity and debate, hindering the field as it seeks to deliver ever higher efficiencies and ultimately a viable new solar photovoltaic technology. In this work, we show that trap-assisted recombination loss of photocurrent is universally present under operational conditions in a wide variety of organic solar cell materials including the new non-fullerene electron acceptor systems currently breaking all efficiency records. The trap-assisted recombination is found to be induced by states lying 0.35-0.6 eV below the transport edge, acting as deep trap states at light intensities equivalent to 1 sun. Apart from limiting the photocurrent, we show that the associated trap-assisted recombination via these comparatively deep traps is also responsible for ideality factors between 1 and 2, shedding further light on another open and important question as to the fundamental working principles of organic solar cells. Our results also provide insights for avoiding trap-induced losses in related indoor photovoltaic and photodetector applications.
A large multiethnic GWAS meta-analysis of cataract identifies new risk loci and sex-specific effects
Authors: Choquet Hélène , Melles Ronald B. , Anand Deepti , Yin Jie , Cuellar-Partida Gabriel , Wang Wei ,   23andMe Research Team, Hoffmann Thomas J. , Nair K. Saidas , Hysi Pirro G. , Lachke Salil A. , Jorgenson Eric
Published: June 2021

Cataract is the leading cause of blindness among the elderly worldwide and cataract surgery is one of the most common operations performed in the United States. As the genetic etiology of cataract formation remains unclear, we conducted a multiethnic genome-wide association meta-analysis, combining results from the GERA and UK Biobank cohorts, and tested for replication in the 23andMe research cohort. We report 54 genome-wide significant loci, 37 of which were novel. Sex-stratified analyses identified CASP7 as an additional novel locus specific to women. We show that genes within or near 80% of the cataract-associated loci are significantly expressed and/or enriched-expressed in the mouse lens across various spatiotemporal stages as per iSyTE analysis. Furthermore, iSyTE shows 32 candidate genes in the associated loci have altered gene expression in 9 different gene perturbation mouse models of lens defects/cataract, suggesting their relevance to lens biology. Our work provides further insight into the complex genetic architecture of cataract susceptibility.
Recent advanced applications of ion-gel in ionic-gated transistor
Authors: Wang Depeng , Zhao Shufang , Yin Ruiyang , Li Linlin , Lou Zheng , Shen Guozhen
Published: June 2021

Diversified regulation of electrons have received much attention to realize a multi-functional transistor, and it is crucial to have a considerable control over the charge carriers in transistors. Ionic gel, as the dielectric material in transistors, facilitates a large capacitance, and high induced-carrier concentrations. This review presents the recent progress in ionic-gated transistors (IGTs) that have good mechanical stability as well as high physical and chemical stability. We first briefly introduce the various applications of IGTs in sensors, neuromorphic transistors, organic transistor circuits, and health detection. Finally, the future perspectives of IGTs are discussed and some possible solutions to the challenges are also proposed.
Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics
Authors: Stojanović Stevan D. , Fuchs Maximilian , Liang Chunguang , Schmidt Kevin , Xiao Ke , Just Annette , Pfanne Angelika , Pich Andreas , Warnecke Gregor , Braubach Peter , Petzold Christina , Jonigk Danny , Distler Jörg H. W. , Fiedler Jan , Thum Thomas , Kunz Meik
Published: June 2021

The family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the characterization of RBPs using multi-sources data information and comparative molecular network bioinformatics followed by wet-lab validation studies. Data mining of bulk RNA-Sequencing data of tissues of patients with IPF identified Quaking (QKI) as a significant downregulated RBP. Cell-type specific expression was confirmed by single-cell RNA-Sequencing analysis of IPF patient data. We systematically analyzed the molecular interaction network around QKI and its functional interplay with microRNAs (miRs) in human lung fibroblasts and discovered a novel regulatory miR-506-QKI axis contributing to the pathogenesis of IPF. The in silico results were validated by in-house experiments applying model systems of miR and lung biology. This study supports an understanding of the intrinsic molecular mechanisms of IPF regulated by the miR-506-QKI axis. Initially applied to human lung disease, the herein presented integrative in silico data mining approach can be adapted to other disease entities, underlining its practical relevance in RBP research.
Social-ecological filters drive the functional diversity of beetles in homegardens of campesinos and migrants in the southern Andes
Authors: Ibarra José Tomás , Caviedes Julián , Altamirano Tomás A. , Urra Romina , Barreau Antonia , Santana Francisca
Published: June 2021

Homegardens are coupled social-ecological systems that act as biodiversity reservoirs while contributing to local food sovereignty. These systems are characterized by their structural complexity, while involving management practices according to gardener’s cultural origin. Social–ecological processes in homegardens may act as filters of species’ functional traits, and thus influence the species richness-functional diversity relationship of critical agroecosystem components like beetles (Coleoptera). We tested the species richness-functional diversity relationship of beetle communities and examined whether habitat structure across different levels, sociodemographic profiles, and management practices act as filters in homegardens in a Global Biodiversity Hotspot, Chile. For 100 homegardens (50 campesino and 50 migrant), we sampled beetles and habitat attributes, and surveyed gardeners’ sociodemographic profiles and management practices. We recorded 85 beetle species and found a positive relationship between species richness and functional richness that saturated when functionally similar species co-occur more often than expected by chance, indicating functional redundancy in species-rich homegardens. Gardener origin (campesino/migrant), homegarden area (m2), structural complexity (index), and pest control strategy (natural, chemical, or none) were the most influential social–ecological filters that selectively remove beetle species according to their functional traits. We discuss opportunities in homegarden management for strengthening local functional diversity and resilience under social-environmental changes.
Peptide profiling in cow urine reveals molecular signature of physiology-driven pathways and in-silico predicted bioactive properties
Authors: Kumar Rohit , Ali Syed Azmal , Singh Sumit Kumar , Bhushan Vanya , Kaushik Jai Kumar , Mohanty Ashok Kumar , Kumar Sudarshan
Published: June 2021

Peptidomics allows the identification of peptides that are derived from proteins. Urinary peptidomics has revolutionized the field of diagnostics as the samples represent complete systemic changes happening in the body. Moreover, it can be collected in a non-invasive manner. We profiled the peptides in urine collected from different physiological states (heifer, pregnancy, and lactation) of Sahiwal cows. Endogenous peptides were extracted from 30 individual cows belonging to three groups, each group comprising of ten animals (biological replicates n = 10). Nano Liquid chromatography Mass spectrometry (nLC-MS/MS) experiments revealed 5239, 4774, and 5466 peptides in the heifer, pregnant and lactating animals respectively. Urinary peptides of <10 kDa size were considered for the study. Peptides were extracted by 10 kDa MWCO filter. Sequences were identified by scanning the MS spectra ranging from 200 to 2200 m/z. The peptides exhibited diversity in sequences across different physiological states and in-silico experiments were conducted to classify the bioactive peptides into anti-microbial, anti-inflammatory, anti-hypertensive, and anti-cancerous groups. We have validated the antimicrobial effect of urinary peptides on Staphylococcus aureus and Escherichia coli under an in-vitro experimental set up. The origin of these peptides was traced back to certain proteases viz. MMPs, KLKs, CASPs, ADAMs etc. which were found responsible for the physiology-specific peptide signature of urine. Proteins involved in extracellular matrix structural constituent (GO:0005201) were found significant during pregnancy and lactation in which tissue remodeling is extensive. Collagen trimers were prominent molecules under cellular component category during lactation. Homophilic cell adhesion was found to be an important biological process involved in embryo attachment during pregnancy. The in-silico study also highlighted the enrichment of progenitor proteins on specific chromosomes and their relative expression in context to specific physiology. The urinary peptides, precursor proteins, and proteases identified in the study offers a base line information in healthy cows which can be utilized in biomarker discovery research for several pathophysiological studies.
Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry
Authors: Mannar Dhiraj , Leopold Karoline , Subramaniam Sriram
Published: June 2021

The SARS-CoV-2 spike glycoprotein is a focal point for vaccine immunogen and therapeutic antibody design, and also serves as a critical antigen in the evaluation of immune responses to COVID-19. A common feature amongst enveloped viruses such as SARS-CoV-2 and HIV-1 is the propensity for displaying host-derived glycans on entry spike proteins. Similarly displayed glycosylation motifs can serve as the basis for glyco-epitope mediated cross-reactivity by antibodies, which can have important implications on virus neutralization, antibody-dependent enhancement (ADE) of infection, and the interpretation of antibody titers in serological assays. From a panel of nine anti-HIV-1 gp120 reactive antibodies, we selected two (PGT126 and PGT128) that displayed high levels of cross-reactivity with the SARS-CoV-2 spike. We report that these antibodies are incapable of neutralizing pseudoviruses expressing SARS-CoV-2 spike proteins and are unlikely to mediate ADE via FcγRII receptor engagement. Nevertheless, ELISA and other immunoreactivity experiments demonstrate these antibodies are capable of binding the SARS-CoV-2 spike in a glycan-dependent manner. These results contribute to the growing literature surrounding SARS-CoV-2 S cross-reactivity, as we demonstrate the ability for cross-reactive antibodies to interfere in immunoassays.
A novel bone-thinning technique for transcranial stimulation motor-evoked potentials in rats
Authors: Maeda Yuyo , Otsuka Takashi , Mitsuhara Takafumi , Okazaki Takahito , Yuge Louis , Takeda Masaaki
Published: June 2021

Transcranial electrical stimulated motor-evoked potentials (tcMEPs) are widely used to evaluate motor function in humans, and even in animal studies, tcMEPs are used to evaluate neurological dysfunction. However, there is a dearth of reports on extended tcMEP recordings in both animal models and humans. Therefore, this study examined a new technique for stably recording tcMEPs over several weeks in six healthy female Sprague–Dawley rats. We thinned the skull bone using the skull base and spinal surgery technique to reduce electrical resistance for electrical stimulation. tcMEPs were recorded on days 1, 7, 14, 21, and 28 after surgery. The onset latency and amplitude of tcMEPs from the hindlimbs were recorded and evaluated, and histological analysis was performed. Stable amplitude and onset latency could be recorded over several weeks, and histological analysis indicated no complications attributable to the procedure. Thus, our novel technique allows for less invasive, safer, easier, and more stable extended tcMEP recordings than previously reported techniques. The presently reported technique may be applied to the study of various nerve injury models in rats: specifically, to evaluate the degree of nerve dysfunction and recovery in spinal cord injury, cerebral infarction, and brain contusion models.
Life-course trajectories of weight and their impact on the incidence of type 2 diabetes
Authors: Yacamán-Méndez Diego , Trolle-Lagerros Ylva , Zhou Minhao , Monteiro Ponce de Leon Antonio , Gudjonsdottir Hrafnhildur , Tynelius Per , Lager Anton
Published: June 2021

Although exposure to overweight and obesity at different ages is associated to a higher risk of type 2 diabetes, the effect of different patterns of exposure through life remains unclear. We aimed to characterize life-course trajectories of weight categories and estimate their impact on the incidence of type 2 diabetes. We categorized the weight of 7203 participants as lean, normal or overweight at five time-points from ages 7–55 using retrospective data. Participants were followed for an average of 19 years for the development of type 2 diabetes. We used latent class analysis to describe distinctive trajectories and estimated the risk ratio, absolute risk difference and population attributable fraction (PAF) associated to different trajectories using Poisson regression. We found five distinctive life-course trajectories. Using the stable-normal weight trajectory as reference, the stable overweight, lean increasing weight, overweight from early adulthood and overweight from late adulthood trajectories were associated to higher risk of type 2 diabetes. The estimated risk ratios and absolute risk differences were statistically significant for all trajectories, except for the risk ratio of the lean increasing trajectory group among men. Of the 981 incident cases of type 2 diabetes, 47.4% among women and 42.9% among men were attributable to exposure to any life-course trajectory different from stable normal weight. Most of the risk was attributable to trajectories including overweight or obesity at any point of life (36.8% of the cases among women and 36.7% among men). The overweight from early adulthood trajectory had the highest impact (PAF: 23.2% for woman and 28.5% for men). We described five distinctive life-course trajectories of weight that were associated to increased risk of type 2 diabetes over 19 years of follow-up. The variability of the effect of exposure to overweight and obesity on the risk of developing type 2 diabetes was largely explained by exposure to the different life-course trajectories of weight.
Metastable states in plateaus and multi-wave epidemic dynamics of Covid-19 spreading in Italy
Authors: Campi Gaetano , Mazziotti Maria Vittoria , Valletta Antonio , Ravagnan Giampietro , Marcelli Augusto , Perali Andrea , Bianconi Antonio
Published: June 2021

The control of Covid 19 epidemics by public health policy in Italy during the first and the second epidemic waves has been driven by using reproductive number Rt(t) to identify the supercritical (percolative), the subcritical (arrested), separated by the critical regime. Here we show that to quantify the Covid-19 spreading rate with containment measures there is a need of a 3D expanded parameter space phase diagram built by the combination of Rt(t) and doubling time Td(t). In this space we identify the Covid-19 dynamics in Italy and its administrative Regions. The supercritical regime is mathematically characterized by (i) the power law of Td vs. [Rt(t) − 1] and (ii) the exponential behaviour of Td vs. time, either in the first and in the second wave. The novel 3D phase diagram shows clearly metastable states appearing before and after the second wave critical regime. for loosening quarantine and tracing of actives cases. The metastable states are precursors of the abrupt onset of a next nascent wave supercritical regime. This dynamic description allows epidemics predictions needed by policymakers interested to point to the target "zero infections" with the elimination of SARS-CoV-2, using the Finding mobile Tracing policy joint with vaccination-campaign, in order to avoid the emergence of recurrent new variants of SARS-CoV-2 virus, accompined by recurrent long lockdowns, with large economical losses, and large number of fatalities.
Drug–drug interactions between treatment specific pharmacotherapy and concomitant medication in patients with COVID-19 in the first wave in Spain
Authors: Cantudo-Cuenca M. D. , Gutiérrez-Pizarraya Antonio , Pinilla-Fernández Ana , Contreras-Macías Enrique , Fernández‑Fuertes M. , Lao‑Domínguez F. A , Rincón Pilar , Pineda Juan Antonio , Macías Juan , Morillo-Verdugo Ramón
Published: June 2021

Primary aim was to assess prevalence and severity of potential and real drug–drug interactions (DDIs) among therapies for COVID-19 and concomitant medications in hospitalized patients with confirmed SARS-CoV-2 infection. The secondary aim was to analyze factors associated with rDDIs. An observational single center cohort study conducted at a tertiary hospital in Spain from March 1st to April 30th. rDDIs refer to interaction with concomitant drugs prescribed during hospital stay whereas potential DDIs (pDDIs) refer to those with domiciliary medication. DDIs checked with The University of Liverpool resource. Concomitant medications were categorized according to the Anatomical Therapeutic Chemical classification system. Binomial logistic regression was carried out to identify factors associated with rDDIs. A total of 174 patients were analyzed. DDIs were detected in 152 patients (87.4%) with a total of 417 rDDIs between COVID19-related drugs and involved hospital concomitant medication (60 different drugs) while pDDIs were detected in 105 patients (72.9%) with a total of 553 pDDIs. From all 417 rDDIs, 43.2% (n = 180) were associated with lopinavir/ritonavir and 52.9% (n = 221) with hydroxychloroquine, both of them the most prescribed (106 and 165 patients, respectively). The main mechanism of interaction observed was QTc prolongation. Clinically relevant rDDIs were identified among 81.1% (n = 338) (‘potential interactions’) and 14.6% (n = 61) (contraindicated) of the patients. Charlson index (OR 1.34, 95% IC 1.02–1.76) and number of drugs prescribed during admission (OR 1.42, 95% IC 1.12–1.81) were independently associated with rDDIs. Prevalence of patients with real and pDDIs was high, especially those clinically relevant. Both comorbidities and polypharmacy were found as risk factors independently associated with DDIs development.
Pre-transplant donor-reactive IL-21 producing T cells as a tool to identify an increased risk for acute rejection
Authors: Mendoza Rojas Aleixandra , van Gelder Teun , de Kuiper Ronella , Reijerkerk Derek , Clahsen-van Groningen Marian C. , Hesselink Dennis A. , Baan Carla C. , van Besouw Nicole M.
Published: June 2021

Pre-transplant screening focuses on the detection of anti-HLA alloantibodies. Previous studies have shown that IFN-γ and IL-21 producing T cells are associated with the development of acute rejection (AR). The aim of this study, was to assess whether pre-transplant donor-reactive T cells and/or B cells are associated with increased rejection risk. Samples from 114 kidney transplant recipients (transplanted between 2010 and 2013) were obtained pre-transplantation. The number of donor-reactive IFN-γ and IL-21 producing cells was analyzed by ELISPOT assay. The presence of donor specific antibodies (DSA) was also determined before transplantation. Numbers of donor-reactive IFN-γ producing cells were similar in patients with or without AR whereas those of IL-21 producing cells were higher in patients with AR (p = 0.03). Significantly more patients with AR [6/30(20%)] had detectable DSA compared to patients without AR [5/84(5.9%), p = 0.03]. Multivariate logistic regression showed that donor age (OR 1.06), pre-transplant DSA (OR 5.61) and positive IL-21 ELISPOT assay (OR 2.77) were independent predictors of an increased risk for the development of AR. Aside from an advanced donor-age and pre-transplant DSA, also pre-transplant donor-reactive IL-21 producing cells are associated with the development of AR after transplantation.
A multi-method approach to modeling COVID-19 disease dynamics in the United States
Authors: Mokhtari Amir , Mineo Cameron , Kriseman Jeffrey , Kremer Pedro , Neal Lauren , Larson John
Published: June 2021

In this paper, we proposed a multi-method modeling approach to community-level spreading of COVID-19 disease. Our methodology was composed of interconnected age-stratified system dynamics models in an agent-based modeling framework that allowed for a granular examination of the scale and severity of disease spread, including metrics such as infection cases, deaths, hospitalizations, and ICU usage. Model parameters were calibrated using an optimization technique with an objective function to minimize error associated with the cumulative cases of COVID-19 during a training period between March 15 and October 31, 2020. We outlined several case studies to demonstrate the model’s state- and local-level projection capabilities. We further demonstrated how model outcomes could be used to evaluate perceived levels of COVID-19 risk across different localities using a multi-criteria decision analysis framework. The model’s two, three, and four week out-of-sample projection errors varied on a state-by-state basis, and generally increased as the out-of-sample projection period was extended. Additionally, the prediction error in the state-level projections was generally due to an underestimation of cases and an overestimation of deaths. The proposed modeling approach can be used as a virtual laboratory to investigate a wide range of what-if scenarios and easily adapted to future high-consequence public health threats.
Changes in electromyographic activity, mechanical power, and relaxation rates following inspiratory ribcage muscle fatigue
Authors: Sarmento Antonio , Fregonezi Guilherme , Lira Maria , Marques Layana , Pennati Francesca , Resqueti Vanessa , Aliverti Andrea
Published: June 2021

Muscle fatigue is a complex phenomenon enclosing various mechanisms. Despite technological advances, these mechanisms are still not fully understood in vivo. Here, simultaneous measurements of pressure, volume, and ribcage inspiratory muscle activity were performed non-invasively during fatigue (inspiratory threshold valve set at 70% of maximal inspiratory pressure) and recovery to verify if inspiratory ribcage muscle fatigue (1) leads to slowing of contraction and relaxation properties of ribcage muscles and (2) alters median frequency and high-to-low frequency ratio (H/L). During the fatigue protocol, sternocleidomastoid showed the fastest decrease in median frequency and slowest decrease in H/L. Fatigue was also characterized by a reduction in the relative power of the high-frequency and increase of the low-frequency. During recovery, changes in mechanical power were due to changes in shortening velocity with long-lasting reduction in pressure generation, and slowing of relaxation [i.e., tau (τ), half-relaxation time (½RT), and maximum relaxation rate (MRR)] was observed with no significant changes in contractile properties. Recovery of median frequency was faster than H/L, and relaxation rates correlated with shortening velocity and mechanical power of inspiratory ribcage muscles; however, with different time courses. Time constant of the inspiratory ribcage muscles during fatigue and recovery is not uniform (i.e., different inspiratory muscles may have different underlying mechanisms of fatigue), and MRR, ½RT, and τ are not only useful predictors of inspiratory ribcage muscle recovery but may also share common underlying mechanisms with shortening velocity.
The urgency of resuming disrupted dog rabies vaccination campaigns: a modeling and cost-effectiveness analysis
Authors: Kunkel Amber , Jeon Seonghye , Joseph Haim C. , Dilius Pierre , Crowdis Kelly , Meltzer Martin I. , Wallace Ryan
Published: June 2021

Dog vaccination is a cost-effective approach to preventing human rabies deaths. In Haiti, the last nation-wide dog vaccination campaign occurred in 2018. We estimated the number of human lives that could be saved by resuming dog vaccination in 2021 compared to 2022 and compared the cost-effectiveness of these two scenarios. We modified a previously published rabies transmission and economic model to estimate trends in dog and human rabies cases in Haiti from 2005 to 2025, with varying assumptions about when dog vaccinations resume. We compared model outputs to surveillance data on human rabies deaths from 2005 to 2020 and animal rabies cases from 2018 to 2020. Model predictions and surveillance data both suggest a 5- to 8-fold increase in animal rabies cases occurred in Haiti’s capital city between Fall 2019 and Fall 2020. Restarting dog vaccination in Haiti in 2021 compared to 2022 could save 285 human lives and prevent 6541 human rabies exposures over a five-year period. It may also decrease program costs due to reduced need for human post-exposure prophylaxis. These results show that interruptions in dog vaccination campaigns before elimination is achieved can lead to significant human rabies epidemics if not promptly resumed.
A human isogenic iPSC-derived cell line panel identifies major regulators of aberrant astrocyte proliferation in Down syndrome
Authors: Kawatani Keiji , Nambara Toshihiko , Nawa Nobutoshi , Yoshimatsu Hidetaka , Kusakabe Haruna , Hirata Katsuya , Tanave Akira , Sumiyama Kenta , Banno Kimihiko , Taniguchi Hidetoshi , Arahori Hitomi , Ozono Keiichi , Kitabatake Yasuji
Published: June 2021

Astrocytes exert adverse effects on the brains of individuals with Down syndrome (DS). Although a neurogenic-to-gliogenic shift in the fate-specification step has been reported, the mechanisms and key regulators underlying the accelerated proliferation of astrocyte precursor cells (APCs) in DS remain elusive. Here, we established a human isogenic cell line panel based on DS-specific induced pluripotent stem cells, the XIST-mediated transcriptional silencing system in trisomic chromosome 21, and genome/chromosome-editing technologies to eliminate phenotypic fluctuations caused by genetic variation. The transcriptional responses of genes observed upon XIST induction and/or downregulation are not uniform, and only a small subset of genes show a characteristic expression pattern, which is consistent with the proliferative phenotypes of DS APCs. Comparative analysis and experimental verification using gene modification reveal dose-dependent proliferation-promoting activity of DYRK1A and PIGP on DS APCs. Our collection of human isogenic cell lines provides a comprehensive set of cellular models for further DS investigations.
Central amygdala circuitry modulates nociceptive processing through differential hierarchical interaction with affective network dynamics
Authors: Wank Isabel , Pliota Pinelopi , Badurek Sylvia , Kraitsy Klaus , Kaczanowska Joanna , Griessner Johannes , Kreitz Silke , Hess Andreas , Haubensak Wulf
Published: June 2021

The central amygdala (CE) emerges as a critical node for affective processing. However, how CE local circuitry interacts with brain wide affective states is yet uncharted. Using basic nociception as proxy, we find that gene expression suggests diverging roles of the two major CE neuronal populations, protein kinase C δ-expressing (PKCδ+) and somatostatin-expressing (SST+) cells. Optogenetic (o)fMRI demonstrates that PKCδ+/SST+circuits engage specific separable functional subnetworks to modulate global brain dynamics by a differential bottom-up vs. top-down hierarchical mesoscale mechanism. This diverging modulation impacts on nocifensive behavior and may underly CE control of affective processing.
Albumin in patients with liver disease shows an altered conformation
Authors: Paar Margret , Fengler Vera H. , Rosenberg Daniel J. , Krebs Angelika , Stauber Rudolf E. , Oettl Karl , Hammel Michal
Published: June 2021

Human serum albumin (HSA) constitutes the primary transporter of fatty acids, bilirubin, and other plasma compounds. The binding, transport, and release of its cargos strongly depend on albumin conformation, which is affected by bound ligands induced by physiological and pathological conditions. HSA is both highly oxidized and heavily loaded with fatty acids and bilirubin in chronic liver disease. By employing small-angle X-ray scattering we show that HSA from the plasma of chronic liver disease patients undergoes a distinct opening compared to healthy donors. The extent of HSA opening correlates with clinically relevant variables, such as the model of end-stage liver disease score, bilirubin, and fatty acid levels. Although the mild oxidation of HSA in vitro does not alter overall structure, the alteration of patients’ HSA correlates with its redox state. This study connects clinical data with structural visualization of albumin dynamicity in solution and underlines the functional importance of albumin’s inherent flexibility.
Combined antioxidant capped and surface supported redox-sensitive nanoparticles for continuous elimination of multi-metallic species
Authors: Khandelwal Nitin , Darbha Gopala Krishna
Published: June 2021

This work highlights a new strategy for modifying redox-sensitive nanoparticles via combined almond skin extracted antioxidant capping and almond shell biochar surface support for the generation of clean water.
Managing hydrogen bonding in the clathrate hydrate of the 1-pentanol guest molecule
Authors: Lee Byeonggwan , Kim Jeongtak , Shin Kyuchul , Park Ki Hun , Cha Minjun , Alavi Saman , Ripmeester John A.
Published: June 2021

1-pentanol, long-chain alcohol molecule, can be encaged in the clathrate hydrate by managing the destabilizing influence of guest–host hydrogen bonding.
Three-step Förster resonance energy transfer on an amyloid fibril scaffold
Authors: Gorbenko Galyna , Zhytniakivska Olga , Vus Kateryna , Tarabara Uliana , Trusova Valeriya
Published: June 2021

The energy transfer chain consisting of four fluorochromes is capable of differentiating between the amyloid and non-fibrillized states of insulin.
Carbon monoxide as an intermediate product in the photocatalytic steam reforming of methane with lanthanum-doped sodium tantalate
Authors: Sarwana Wirya , Anzai Akihiko , Takami Daichi , Yamamoto Akira , Yoshida Hisao
Published: June 2021

A NaTaO3:La photocatalyst without a cocatalyst can produce carbon monoxide as a partially oxidized product in photocatalytic steam reforming of methane (PSRM) at around room temperature.
Self-assembly of silicoaluminophosphate nanocrystals in biphasic media with a water-insoluble structure-directing agent
Authors: Ding Hongxin , Zhou Qiuming , Li Junfen , Zhu Kake , Fan Weibin
Published: June 2021

Toluene/water media enable the use of hydrophobic tri-n-heptylamine as an organic structure-directing agent for the synthesis of hierarchically porous SAPO-31 that outperforms conventional one inn-dodecane hydroisomerization.
Dual role of silver in a fluorogenic N-squaraine probe based on Ag(i)–π interactions
Authors: Vega Manel , Blasco Salvador , García-España Enrique , Soberats Bartolomé , Frontera Antonio , Rotger Carmen , Costa Antonio
Published: June 2021

Cyano-N-squaraine 1 is a cinderella molecule that can offer a bright fluorescence turn-on response when an appropriate silver shoe was used.
Synthesis and catalytic activity of palladium complexes bearing N-heterocyclic carbenes (NHCs) and 1,4,7-triaza-9-phosphatricyclo[5.3.2.1]tridecane (CAP) ligands
Authors: Scattolin Thomas , Voloshkin Vladislav A. , Martynova Ekaterina , Vanden Broeck Sofie M. P. , Beliš Marek , Cazin Catherine S. J. , Nolan Steven P.
Published: June 2021

Two synthetic approaches to cis-[Pd(CAP)(NHC)Cl2] are reported. The catalytic performance of these complexes in the Buchwald–Hartwig aryl amination reaction showed the complex bearing IPr to be the most efficient.
Electron transfer mechanism of peroxydisulfate activation by sewage sludge-derived biochar for enhanced degradation of sulfamethoxazole
Authors: Pei Xuan-Yuan , Ren Hong-Yu , Xing De-Feng , Xie Guo-Jun , Cao Guang-Li , Meng Jia , Ren Nan-Qi , Liu Bing-Feng
Published: June 2021

The electron-transfer process is the main pathway occurring in the BC800/PDS system and the singlet oxygen pathway is determined to have little contribution to the oxidation of SMX.
Anharmonicity and ultralow thermal conductivity in layered oxychalcogenides BiAgOCh (Ch = S, Se, and Te)
Authors: Li Jingyu , Zhai Wenya , Zhang Chi , Yan Yuli , Liu Peng-Fei , Yang Gui
Published: June 2021

Understanding the lattice dynamics and low thermal conductivities of oxychalcogenide materials is critical to the development of a new generation of better thermoelectric oxide materials.
NIR luminescence lifetime nanothermometry based on phonon assisted Yb3+–Nd3+energy transfer
Authors: Maciejewska K. , Bednarkiewicz A. , Marciniak L.
Published: June 2021

Luminescence thermometry in biomedical sciences is a highly desirable, but also highly challenging and demanding technology.
Efficiently selective oxidation of glycerol by BiQDs/BiOBr–Ov: promotion of molecular oxygen activation by Bi quantum dots and oxygen vacancies
Authors: Yue Chengguang , Li Chenhao , Zhang Pingbo , Fan Mingming , Haryono Agus , Leng Yan , Dong Yuming , Jiang Pingping
Published: June 2021

BiQDs and Ov can promote the activation of O2 to make BiQDs/BiOBr–Ov catalyze the selective oxidation of glycerol efficiently.
Plasmonic enhancement of molecular hydrogen dissociation on metallic magnesium nanoclusters
Authors: Douglas-Gallardo Oscar A. , Box Connor L. , Maurer Reinhard J.
Published: June 2021

The optical and catalytic properties of magnesium nanoclusters are characterized in the context of plasmonic catalysis. Ab initio simulations reveal the propensity for plasmonic enhancement of hydrogen dissociation and evolution.
Peptide foldamer-based self-assembled nanostructures containing cyclic beta-amino acids
Authors: Szefczyk Monika
Published: June 2021

This minireview presents the current state of knowledge in the field of peptide foldamer-based self-assembled nanostructures containing cyclic beta-amino acids.
Synthesis of substituted 1,2-dihydroisoquinolines via Ni(ii) and Cu(i)/Ag(i) catalyzed double nucleophilic addition of arylamines to ortho-alkynyl donor–acceptor cyclopropanes (o-ADACs)
Authors: Unnava Ramanjaneyulu , Chahal Kapil , Reddy Kallu Rajender
Published: June 2021

Synthesis of substituted 1,2-dihydroisoquinolines via double nucleophilic addition of primary arylamines to ortho-alkynyl donor–acceptor cyclopropanes (o-ADACs) in the presence of a catalytic Ni(ii) and Cu(i)/Ag(i) system has been developed.
Photopolymerized poly(l-lactide-b-N-vinyl-2-pyrrolidone) network resists cell adhesion in situ
Authors: Wang Yong , Lan Xiaorong , Zuo Shuyin , Zou Yafeng , Li Sai , Tang Zhonglan , Wang Yunbing
Published: June 2021

The poly(l-lactide-b-N-vinyl-2-pyrrolidone) network could be formed by UV curing, and resist the adhesion of L929 fibroblasts. It could be used in the field of biological anti-fouling material with customization requirements.
Complex molecular logic gates from simple molecules
Authors: Quintana-Romero Osvaldo J. , Ariza-Castolo Armando
Published: June 2021

Herein we describe a protocol to mimic an electronic device. The MLG could function as a transmitter of information at a molecular level and this could be read using the variation of the magnetic field in the molecules.
Titanium anodizing in a choline dihydrogencitrate salt–oxalic acid deep eutectic solvent: a step towards green chemistry in surface finishing of titanium and its alloys
Authors: Winiarski Juliusz , Niciejewska Anna , Górnik Monika , Jakubowski Jakub , Tylus Włodzimierz , Szczygieł Bogdan
Published: June 2021

Fabrication of nanometric color TiO2 layers through polarization of titanium in a choline dihydrogencitrate–oxalic acid DES anodizing bath.
Strategic engineering of alkyl spacer length for a pH-tolerant lysosome marker and dual organelle localization
Authors: Biswas Suprakash , Dutta Tanoy , Silswal Akshay , Bhowal Rohit , Chopra Deepak , Koner Apurba L.
Published: June 2021

A series naphthalimide-based fluorophores were designed by alkyl spacer length engineering to discover a pH-tolerant lysosomal marker. This approach also allows to probe lysosome-related organelles inC. elegansand communication between organelles.
Accessing lanthanide-based, in situ illuminated optical turn-on probes by modulation of the antenna triplet state energy
Authors: Cosby Alexia G. , Woods Joshua J. , Nawrocki Patrick , Sørensen Thomas J. , Wilson Justin J. , Boros Eszter
Published: June 2021

The rational, analyte-mediated modulation of the relative energy of the lanthanide-sensitizing triplet state produces Tb-based luminescence, observable by a conventional optical imager in presence of the Cherenkov radiation emitting radioisotope 18F.