bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilevel polarization switching in ferroelectric thin films
Authors: Sarott Martin F. , Rossell Marta D. , Fiebig Manfred , Trassin Morgan 
Published: June 2022

AbstractFerroic order is characterized by hystereses with two remanent states and therefore inherently binary. The increasing interest in materials showing non-discrete responses, however, calls for a paradigm shift towards continuously tunable remanent ferroic states. Device integration for oxide nanoelectronics furthermore requires this tunability at the nanoscale. Here we demonstrate that we can arbitrarily set the remanent ferroelectric polarization at nanometric dimensions. We accomplish this in ultrathin epitaxial PbZr0.52Ti0.48O3 films featuring a dense pattern of decoupled nanometric 180° domains with a broad coercive-field distribution. This multilevel switching is achieved by driving the system towards the instability at the morphotropic phase boundary. The phase competition near this boundary in combination with epitaxial strain increases the responsiveness to external stimuli and unlocks new degrees of freedom to nano-control the polarization. We highlight the technological benefits of non-binary switching by demonstrating a quasi-continuous tunability of the non-linear optical response and of tunnel electroresistance.
A streamlined platform for analyzing tera-scale DDA and DIA mass spectrometry data enables highly sensitive immunopeptidomics
Authors: Xin Lei , Qiao Rui , Chen Xin , Tran Hieu , Pan Shengying , Rabinoviz Sahar , Bian Haibo , He Xianliang , Morse Brenton , Shan Baozhen , Li Ming 
Published: June 2022

AbstractIntegrating data-dependent acquisition (DDA) and data-independent acquisition (DIA) approaches can enable highly sensitive mass spectrometry, especially for imunnopeptidomics applications. Here we report a streamlined platform for both DDA and DIA data analysis. The platform integrates deep learning-based solutions of spectral library search, database search, and de novo sequencing under a unified framework, which not only boosts the sensitivity but also accurately controls the specificity of peptide identification. Our platform identifies 5-30% more peptide precursors than other state-of-the-art systems on multiple benchmark datasets. When evaluated on immunopeptidomics datasets, we identify 1.7-4.1 and 1.4-2.2 times more peptides from DDA and DIA data, respectively, than previously reported results. We also discover six T-cell epitopes from SARS-CoV-2 immunopeptidome that might represent potential targets for COVID-19 vaccine development. The platform supports data formats from all major instruments and is implemented with the distributed high-performance computing technology, allowing analysis of tera-scale datasets of thousands of samples for clinical applications.
Rapid and up-scalable manufacturing of gigahertz nanogap diodes
Authors: Loganathan Kalaivanan , Faber Hendrik , Yengel Emre , Seitkhan Akmaral , Bakytbekov Azamat , Yarali Emre , Adilbekova Begimai , AlBatati Afnan , Lin Yuanbao , Felemban Zainab , Yang Shuai , Li Weiwei , Georgiadou Dimitra G. , Shamim Atif , Lidorikis Elefterios , Anthopoulos Thomas D. 
Published: June 2022

AbstractThe massive deployment of fifth generation and internet of things technologies requires precise and high-throughput fabrication techniques for the mass production of radio frequency electronics. We use printable indium-gallium-zinc-oxide semiconductor in spontaneously formed self-aligned <10 nm nanogaps and flash-lamp annealing to demonstrate rapid manufacturing of nanogap Schottky diodes over arbitrary size substrates operating in 5 G frequencies. These diodes combine low junction capacitance with low turn-on voltage while exhibiting cut-off frequencies (intrinsic) of >100 GHz. Rectifier circuits constructed with these co-planar diodes can operate at ~47 GHz (extrinsic), making them the fastest large-area electronic devices demonstrated to date.
Viral coinfection promotes tuberculosis immunopathogenesis by type I IFN signaling-dependent impediment of Th1 cell pulmonary influx
Authors: Kang Tae Gun , Kwon Kee Woong , Kim Kyungsoo , Lee Insuk , Kim Myeong Joon , Ha Sang-Jun , Shin Sung Jae 
Published: June 2022

AbstractTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is often exacerbated upon coinfection, but the underlying immunological mechanisms remain unclear. Here, to elucidate these mechanisms, we use an Mtb and lymphocytic choriomeningitis virus coinfection model. Viral coinfection significantly suppresses Mtb-specific IFN-γ production, with elevated bacterial loads and hyperinflammation in the lungs. Type I IFN signaling blockade rescues the Mtb-specific IFN-γ response and ameliorates lung immunopathology. Single-cell sequencing, tissue immunofluorescence staining, and adoptive transfer experiments indicate that viral infection-induced type I IFN signaling could inhibit CXCL9/10 production in myeloid cells, ultimately impairing pulmonary migration of Mtb-specific CD4+ T cells. Thus, our study suggests that augmented and sustained type I IFNs by virus coinfection prior to the pulmonary localization of Mtb-specific Th1 cells exacerbates TB immunopathogenesis by impeding the Mtb-specific Th1 cell influx. Our study highlights a negative function of viral coinfection-induced type I IFN responses in delaying Mtb-specific Th1 responses in the lung.
Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands
Authors: Yoon Yeo-Jun , Kim Donghyun , Tak Kwon Yong , Hwang Seungyeon , Kim Jisun , Sim Nam Suk , Cho Jae-Min , Choi Dojin , Ji Youngmi , Hur Junho K. , Kim Hyunki , Park Jong-Eun , Lim Jae-Yol 
Published: June 2022

AbstractSalivary glands that produce and secrete saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. The long-term maintenance of diverse salivary gland cells in organoids remains problematic. Here, we establish long-term murine and human salivary gland organoid cultures. Murine and human salivary gland organoids express gland-specific genes and proteins of acinar, myoepithelial, and duct cells, and exhibit gland functions when stimulated with neurotransmitters. Furthermore, human salivary gland organoids are established from isolated basal or luminal cells, retaining their characteristics. Single-cell RNA sequencing also indicates that human salivary gland organoids contain heterogeneous cell types and replicate glandular diversity. Our protocol also enables the generation of tumoroid cultures from benign and malignant salivary gland tumor types, in which tumor-specific gene signatures are well-conserved. In this study, we provide an experimental platform for the exploration of precision medicine in the era of tissue regeneration and anticancer treatment.
Integrating 3D genomic and epigenomic data to enhance target gene discovery and drug repurposing in transcriptome-wide association studies
Authors: Khunsriraksakul Chachrit , McGuire Daniel , Sauteraud Renan , Chen Fang , Yang Lina , Wang Lida , Hughey Jordan , Eckert Scott , Dylan Weissenkampen J. , Shenoy Ganesh , Marx Olivia , Carrel Laura , Jiang Bibo , Liu Dajiang J. 
Published: June 2022

AbstractTranscriptome-wide association studies (TWAS) are popular approaches to test for association between imputed gene expression levels and traits of interest. Here, we propose an integrative method PUMICE (Prediction Using Models Informed by Chromatin conformations and Epigenomics) to integrate 3D genomic and epigenomic data with expression quantitative trait loci (eQTL) to more accurately predict gene expressions. PUMICE helps define and prioritize regions that harbor cis-regulatory variants, which outperforms competing methods. We further describe an extension to our method PUMICE +, which jointly combines TWAS results from single- and multi-tissue models. Across 79 traits, PUMICE + identifies 22% more independent novel genes and increases median chi-square statistics values at known loci by 35% compared to the second-best method, as well as achieves the narrowest credible interval size. Lastly, we perform computational drug repurposing and confirm that PUMICE + outperforms other TWAS methods.
Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model
Authors: Li Tianbao , Liu Qi , Chen Zhong , Fang Kun , Huang Furong , Fu Xueqi , Wang Qianben , Jin Victor X. 
Published: June 2022

AbstractKnowledge gaps remain on how nucleosome organization and dynamic reorganization are governed by specific pioneer factors in a genome-wide manner. In this study, we generate over three billons of multi-omics sequencing data to exploit dynamic nucleosome landscape governed by pioneer factors (PFs), FOXA1 and GATA2. We quantitatively define nine functional nucleosome states each with specific characteristic nucleosome footprints in LNCaP prostate cancer cells. Interestingly, we observe dynamic switches among nucleosome states upon androgen stimulation, accompanied by distinct differential (gained or lost) binding of FOXA1, GATA2, H1 as well as many other coregulators. Intriguingly, we reveal a noncanonical pioneer model of GATA2 that it initially functions as a PF binding at the edge of a nucleosome in an inaccessible crowding array. Upon androgen stimulation, GATA2 re-configures an inaccessible to accessible nucleosome state and subsequently acts as a master transcription factor either directly or recruits signaling specific transcription factors to enhance WNT signaling in an androgen receptor (AR)-independent manner. Our data elicit a pioneer and master dual role of GATA2 in mediating nucleosome dynamics and enhancing downstream signaling pathways. Our work offers structural and mechanistic insight into the dynamics of pioneer factors governing nucleosome reorganization.
Novel homozygous nonsense mutation of MLIP and compensatory alternative splicing
Authors: Mezreani Jean , Audet Sébastien , Martin Florence , Charbonneau Jade , Triassi Valérie , Bareke Eric , Laplante Annie , Karamchandani Jason , Massie Rami , Chalk Colin H. , O’Ferrall Erin , Tétreault Martine 
Published: June 2022

AbstractDespite the growing accessibility of clinical sequencing, functional interpretation of variants remains a major hurdle to molecular diagnostics of Mendelian diseases. We aimed to describe a new adult-onset myopathy with muscle weakness and hyperCKemia caused by a nonsense variant in muscular LMNA-interacting protein (MLIP). Following RNA-sequencing, differential expression analysis uncovered a significant downregulation of this gene, which had a surprisingly mild effect on MLIP protein expression. RT-PCR and long-read sequencing (LRS) both support an important transcriptome shift in the patient, where decreased MLIP levels are seemingly due to nonsense-mediated decay of transcripts containing the exon 5 mutation. Moreover, a compensatory mechanism upregulates the functionally lacking isoforms and generates novel transcripts. These results support the recently discovered clinical implications of MLIP variants in myopathies, highlighting for the first time its relevance in adult-onset cases. These results also underline the power of LRS as a tool for the functional assessment of variants of unknown significance (VUS), as well as the definition of accurate isoform profile annotations in a tissue-specific manner.
Impairment of 7F2 osteoblast function by simulated partial gravity in a Random Positioning Machine
Authors: Braveboy-Wagner Justin , Lelkes Peter I. 
Published: June 2022

AbstractThe multifaceted adverse effects of reduced gravity pose a significant challenge to human spaceflight. Previous studies have shown that bone formation by osteoblasts decreases under microgravity conditions, both real and simulated. However, the effects of partial gravity on osteoblasts’ function are less well understood. Utilizing the software-driven newer version of the Random Positioning Machine (RPMSW), we simulated levels of partial gravity relevant to future manned space missions: Mars (0.38 G), Moon (0.16 G), and microgravity (Micro, ~10−3 G). Short-term (6 days) culture yielded a dose-dependent reduction in proliferation and the enzymatic activity of alkaline phosphatase (ALP), while long-term studies (21 days) showed a distinct dose-dependent inhibition of mineralization. By contrast, expression levels of key osteogenic genes (Alkaline phosphatase, Runt-related Transcription Factor 2, Sparc/osteonectin) exhibited a threshold behavior: gene expression was significantly inhibited when the cells were exposed to Mars-simulating partial gravity, and this was not reduced further when the cells were cultured under simulated Moon or microgravity conditions. Our data suggest that impairment of cell function with decreasing simulated gravity levels is graded and that the threshold profile observed for reduced gene expression is distinct from the dose dependence observed for cell proliferation, ALP activity, and mineral deposition. Our study is of relevance, given the dearth of research into the effects of Lunar and Martian gravity for forthcoming space exploration.
Moldable and transferrable conductive nanocomposites for epidermal electronics
Authors: Namkoong Myeong , Guo Heng , Rahman Md Saifur , Wang Daniel , Pfeil Cassandra Jane , Hager Sophia , Tian Limei 
Published: June 2022

AbstractSkin-inspired soft and stretchable electronic devices based on functional nanomaterials have broad applications such as health monitoring, human–machine interface, and the Internet of things. Solution-processed conductive nanocomposites have shown great promise as a building block of soft and stretchable electronic devices. However, realizing conductive nanocomposites with high conductivity, electromechanical stability, and low modulus over a large area at sub-100 μm resolution remains challenging. Here, we report a moldable, transferrable, high-performance conductive nanocomposite comprised of an interpenetrating network of silver nanowires and poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate). The stacked structure of the nanocomposite synergistically integrates the complementary electrical and mechanical properties of the individual components. We patterned the nanocomposite via a simple, low-cost micromolding process and then transferred the patterned large-area electrodes onto various substrates to realize soft, skin-interfaced electrophysiological sensors. Electrophysiological signals measured using the nanocomposite electrodes exhibit a higher signal-to-noise ratio than standard gel electrodes. The nanocomposite design and fabrication approach presented here can be broadly employed for soft and stretchable electronic devices.
Evaluating the policy of closing bars and restaurants in Cataluña and its effects on mobility and COVID19 incidence
Authors: Smith Matthew , Ponce-de-Leon Miguel , Valencia Alfonso 
Published: June 2022

AbstractThe world has gone through unprecedented changes since the global pandemic hit. During the early phase of the pandemic, the absence of known drugs or pharmaceutical treatments forced governments to introduce different policies in order to help reduce contagion rates and manage the economic consequences of the pandemic. This paper analyses the causal impact on mobility and COVID19 incidence from policy makers in Cataluña, Spain. We use anonymized phone-based mobility data together with reported incidence and apply a series of causal impact models frequently used in econometrics and policy evaluation in order to measure the policies impact. We analyse the case of Cataluña and the public policy decision of closing all bars and restaurants down for a 5 week period between 2020-16-10 and 2020-23-11. We find that this decision led to a significant reduction in mobility. It not only led to reductions in mobility but from a behavioural economics standpoint, we highlight how people responded to the policy decision. Moreover, the policy of closing bars and restaurants slowed the incidence rate of COVID19 after a time lag has been taken into account. These findings are significant since governments worldwide want to restrict movements of people in order to slow down COVID19 incidence without infringing on their rights directly.
A global network model of abiotic phosphorus cycling on Earth through time
Authors: Jusino-Maldonado Marcos , Rianço-Silva Rafael , Mondal Javed Akhter , Pasek Matthew , Laneuville Matthieu , Cleaves H. James 
Published: June 2022

AbstractPhosphorus (P) is a crucial structural component of living systems and central to modern bioenergetics. P cycles through terrestrial geochemical reservoirs via complex physical and chemical processes. Terrestrial life has altered these fluxes between reservoirs as it evolved, which is why it is of interest to explore planetary P flux evolution in the absence of biology. This is especially true, since environmental P availability affects life’s ability to alter other geochemical cycles, which could then be an example of niche construction. Understanding how P reservoir transport affects environmental P availability helps parameterize how the evolution of P reservoirs influenced the emergence of life on Earth, and potentially other planetary bodies. Geochemical P fluxes likely change as planets evolve, and element cycling models that take those changes into account can provide insights on how P fluxes evolve abiotically. There is considerable uncertainty in many aspects of modern and historical global P cycling, including Earth’s initial P endowment and distribution after core formation and how terrestrial P interactions between reservoirs and fluxes and their rates have evolved over time. We present here a dynamical box model for Earth’s abiological P reservoir and flux evolution. This model suggests that in the absence of biology, long term planetary geochemical cycling on planets similar to Earth with respect to geodynamism tends to bring P to surface reservoirs, and biology, including human civilization, tends to move P to subductable marine reservoirs.
Differences in complication patterns in subgroups of type 2 diabetes according to insulin resistance and beta-cell function
Authors: Cho Yongin , Seo Seong Ha , Seo Da Hea , Ahn Seong Hee , Hong Seongbin , Huh Byung Wook , Lee Yong-ho , Park Seok Won , Suh Young Ju , Kim So Hun 
Published: June 2022

AbstractThis study aimed to determine whether the patterns of diabetic complications differed when patients with type 2 diabetes mellitus (T2DM) were simply classified according to insulin sensitivity and beta-cell function. This observational study included 8861 patients with T2DM who underwent concurrent testing for fasting glucose, fasting insulin, and one or more diabetic complications. We categorized the patients into four groups according to insulin sensitivity and beta-cell function. Compared with the reference group (mild insulin resistance and beta-cell dysfunction), the “severe beta-cell dysfunction” group had lower odds of chronic kidney disease [adjusted odds ratios (aOR) 0.611]. The “severe insulin resistance” group had higher odds of carotid artery plaque presence (aOR 1.238). The “severe insulin resistance and beta-cell dysfunction” group had significantly higher odds of large fiber neuropathy (aOR 1.397, all p < 0.05). After a median of five years of follow-up, this group distinction did not lead to a difference in risk of new diabetic retinopathy or chronic kidney disease. In addition, there was no significant difference among the groups in plaque progression risk over 8–10 years in the longitudinal follow-up analysis. The patterns of complications differ when patients with T2DM are classified according to insulin resistance and beta-cell dysfunction. However, there were no differences in the risk of developing new complications.
Determination of pholcodine alone or in combination with ephedrine in human plasma using fluorescence spectroscopy
Authors: Elmansi Heba , Belal Fathalla , Magdy Galal 
Published: June 2022

AbstractIn this study, sensitive, facile, and cost-effective spectrofluorimetric approaches were developed for the determination of pholcodine and ephedrine. Method I is a novel spectrofluorimetric method depending on measuring the native fluorescence of pholcodine at 337 nm after excitation at 284 nm over a concentration range of 0.01–2.4 μg/mL. The method sensitivity reached quantitation and detection limits down to 10.0 and 5.0 ng/mL, respectively. Method II relied on the simultaneous estimation of pholcodine and ephedrine using synchronous fluorimetry for the first time. The cited drugs were measured concurrently at 286 and 304 nm for pholcodine and ephedrine, respectively at Δλ of 40 nm without interference. Excellent linear relationship between concentration and response was obtained over the ranges of 0.05–6.0 μg/mL and 0.02–1.0 μg/mL for pholcodine and ephedrine, respectively. The method showed distinct sensitivity and exhibited quantitation limits of 20.0 and 10.0 ng/mL and detection limits of 10.0 and 5.0 ng/mL, respectively. The method was successfully applied to the syrup dosage form. The two developed approaches were also applied to in-vitro plasma samples, showing good bioanalytical applicability and providing further insights for monitoring drug abuse. The proposed methods were validated according to ICHQ2(R1) guidelines. The proposed methodologies' greenness profiles were evaluated using two greenness assessment tools.
Genomic insights of high-risk clones of ESBL-producing Escherichia coli isolated from community infections and commercial meat in southern Brazil
Authors: Soncini João Gabriel Material , Cerdeira Louise , Sano Elder , Koga Vanessa Lumi , Tizura Ariane Tiemy , Tano Zuleica Naomi , Nakazato Gerson , Kobayashi Renata Katsuko Takayama , Aires Caio Augusto Martins , Lincopan Nilton , Vespero Eliana Carolina 
Published: June 2022

AbstractDuring a microbiological and genomic surveillance study conducted to investigate the molecular epidemiology of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli from community-acquired urinary tract infections (UTI) and commercial meat samples, in a Brazilian city with a high occurrence of infections by ESBL-producing bacteria, we have identified the presence of CTX-M (-2, -14, -15, -24, -27 and -55)-producing E. coli of international clones ST38, ST117, ST131 and ST354. The ST131 was more prevalent in human samples, and worryingly the high-risk ST131-C1-M27 was identified in human infections for the first time. We also detected CTX-M-55-producing E. coli ST117 from meat samples (i.e., chicken and pork) and human infections. Moreover, the clinically relevant CTX-M-24-positive E. coli ST354 clone was detected for the first time in human samples. In summary, our results highlight a potential of commercialized meat as a reservoir of high-priority E. coli lineages in the community, whereas the identification of E. coli ST131-C1-M27 indicates that novel pandemic clones have emerged in Brazil, constituting a public health issue.