bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implantable optical fibers for immunotherapeutics delivery and tumor impedance measurement
Authors: Chin Ai Lin , Jiang Shan , Jang Eungyo , Niu Liqian , Li Liwu , Jia Xiaoting , Tong Rong 
Published: August 2021

AbstractImmune checkpoint blockade antibodies have promising clinical applications but suffer from disadvantages such as severe toxicities and moderate patient–response rates. None of the current delivery strategies, including local administration aiming to avoid systemic toxicities, can sustainably supply drugs over the course of weeks; adjustment of drug dose, either to lower systemic toxicities or to augment therapeutic response, is not possible. Herein, we develop an implantable miniaturized device using electrode-embedded optical fibers with both local delivery and measurement capabilities over the course of a few weeks. The combination of local immune checkpoint blockade antibodies delivery via this device with photodynamic therapy elicits a sustained anti-tumor immunity in multiple tumor models. Our device uses tumor impedance measurement for timely presentation of treatment outcomes, and allows modifications to the delivered drugs and their concentrations, rendering this device potentially useful for on-demand delivery of potent immunotherapeutics without exacerbating toxicities.
Tumour-targeted interleukin-12 and entinostat combination therapy improves cancer survival by reprogramming the tumour immune cell landscape
Authors: Hicks Kristin C. , Chariou Paul L. , Ozawa Yohei , Minnar Christine M. , Knudson Karin M. , Meyer Thomas J. , Bian Jing , Cam Margaret , Schlom Jeffrey , Gameiro Sofia R. 
Published: August 2021

AbstractPoorly inflamed carcinomas do not respond well to immune checkpoint blockade. Converting the tumour microenvironment into a functionally inflamed immune hub would extend the clinical benefit of immune therapy to a larger proportion of cancer patients. Here we show, by using comprehensive single-cell transcriptome, proteome, and immune cell analysis, that Entinostat, a class I histone deacetylase inhibitor, facilitates accumulation of the necrosis-targeted recombinant murine immune-cytokine, NHS-rmIL12, in experimental mouse colon carcinomas and poorly immunogenic breast tumours. This combination therapy reprograms the tumour innate and adaptive immune milieu to an inflamed landscape, where the concerted action of highly functional CD8+T cells and activated neutrophils drive macrophage M1-like polarization, leading to complete tumour eradication in 41.7%-100% of cases. Biomarker signature of favourable overall survival in multiple human tumor types shows close resemblance to the immune pattern generated by Entinostat/NHS-rmIL12 combination therapy. Collectively, these findings provide a rationale for combining NHS-IL12 with Entinostat in the clinical setting.
AHR signaling is induced by infection with coronaviruses
Authors: Giovannoni Federico , Li Zhaorong , Remes-Lenicov Federico , Dávola María E. , Elizalde Mercedes , Paletta Ana , Ashkar Ali A. , Mossman Karen L. , Dugour Andrea V. , Figueroa Juan M. , Barquero Andrea A. , Ceballos Ana , Garcia Cybele C. , Quintana Francisco J. 
Published: August 2021

AbstractCoronavirus infection in humans is usually associated to respiratory tract illnesses, ranging in severity from mild to life-threatening respiratory failure. The aryl hydrocarbon receptor (AHR) was recently identified as a host factor for Zika and dengue viruses; AHR antagonists boost antiviral immunity, decrease viral titers and ameliorate Zika-induced pathology in vivo. Here we report that AHR is activated by infection with different coronaviruses, potentially impacting antiviral immunity and lung epithelial cells. Indeed, the analysis of single-cell RNA-seq from lung tissue detected increased expression of AHR and AHR transcriptional targets, suggesting AHR signaling activation in SARS-CoV-2-infected epithelial cells from COVID-19 patients. Moreover, we detected an association between AHR expression and viral load in SARS-CoV-2 infected patients. Finally, we found that the pharmacological inhibition of AHR suppressed the replication in vitro of one of the causative agents of the common cold, HCoV-229E, and the causative agent of the COVID-19 pandemic, SARS-CoV-2. Taken together, these findings suggest that AHR activation is a common strategy used by coronaviruses to evade antiviral immunity and promote viral replication, which may also contribute to lung pathology. Future studies should further evaluate the potential of AHR as a target for host-directed antiviral therapy.
Controllable CO2 electrocatalytic reduction via ferroelectric switching on single atom anchored In2Se3 monolayer
Authors: Ju Lin , Tan Xin , Mao Xin , Gu Yuantong , Smith Sean , Du Aijun , Chen Zhongfang , Chen Changfeng , Kou Liangzhi 
Published: August 2021

AbstractEfficient and selective CO2 electroreduction into chemical fuels promises to alleviate environmental pollution and energy crisis, but it relies on catalysts with controllable product selectivity and reaction path. Here, by means of first-principles calculations, we identify six ferroelectric catalysts comprising transition-metal atoms anchored on In2Se3 monolayer, whose catalytic performance can be controlled by ferroelectric switching based on adjusted d-band center and occupation of supported metal atoms. The polarization dependent activation allows effective control of the limiting potential of CO2 reduction on TM@In2Se3 (TM = Ni, Pd, Rh, Nb, and Re) as well as the reaction paths and final products on Nb@In2Se3 and Re@In2Se3. Interestingly, the ferroelectric switching can even reactivate the stuck catalytic CO2 reduction on Zr@In2Se3. The fairly low limiting potential and the unique ferroelectric controllable CO2 catalytic performance on atomically dispersed transition-metals on In2Se3 clearly distinguish them from traditional single atom catalysts, and open an avenue toward improving catalytic activity and selectivity for efficient and controllable electrochemical CO2 reduction reaction.
Fire-derived phosphorus fertilization of African tropical forests
Authors: Bauters Marijn , Drake Travis W. , Wagner Sasha , Baumgartner Simon , Makelele Isaac A. , Bodé Samuel , Verheyen Kris , Verbeeck Hans , Ewango Corneille , Cizungu Landry , Van Oost Kristof , Boeckx Pascal 
Published: August 2021

AbstractCentral African tropical forests face increasing anthropogenic pressures, particularly in the form of deforestation and land-use conversion to agriculture. The long-term effects of this transformation of pristine forests to fallow-based agroecosystems and secondary forests on biogeochemical cycles that drive forest functioning are poorly understood. Here, we show that biomass burning on the African continent results in high phosphorus (P) deposition on an equatorial forest via fire-derived atmospheric emissions. Furthermore, we show that deposition loads increase with forest regrowth age, likely due to increasing canopy complexity, ranging from 0.4 kg P ha−1 yr−1 on agricultural fields to 3.1 kg P ha−1 yr−1 on old secondary forests. In forest systems, canopy wash-off of dry P deposition increases with rainfall amount, highlighting how tropical forest canopies act as dynamic reservoirs for enhanced addition of this essential plant nutrient. Overall, the observed P deposition load at the study site is substantial and demonstrates the importance of canopy trapping as a pathway for nutrient input into forest ecosystems.
Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity
Authors: Cindy Yang S. Y. , Lien Scott C. , Wang Ben X. , Clouthier Derek L. , Hanna Youstina , Cirlan Iulia , Zhu Kelsey , Bruce Jeffrey P. , El Ghamrasni Samah , Iafolla Marco A. J. , Oliva Marc , Hansen Aaron R. , Spreafico Anna , Bedard Philippe L. , Lheureux Stephanie , Razak Albiruni , Speers Vanessa , Berman Hal K. , Aleshin Alexey , Haibe-Kains Benjamin , Brooks David G. , McGaha Tracy L. , Butler Marcus O. , Bratman Scott V. , Ohashi Pamela S. , Siu Lillian L. , Pugh Trevor J. 
Published: August 2021

AbstractSerial circulating tumor DNA (ctDNA) monitoring is emerging as a non-invasive strategy to predict and monitor immune checkpoint blockade (ICB) therapeutic efficacy across cancer types. Yet, limited data exist to show the relationship between ctDNA dynamics and tumor genome and immune microenvironment in patients receiving ICB. Here, we present an in-depth analysis of clinical, whole-exome, transcriptome, and ctDNA profiles of 73 patients with advanced solid tumors, across 30 cancer types, from a phase II basket clinical trial of pembrolizumab (NCT02644369) and report changes in genomic and immune landscapes (primary outcomes). Patients stratified by ctDNA and tumor burden dynamics correspond with survival and clinical benefit. High mutation burden, high expression of immune signatures, and mutations inBRCA2are associated with pembrolizumab molecular sensitivity, while abundant copy-number alterations andB2Mloss-of-heterozygosity corresponded with resistance. Upon treatment, induction of genes expressed by T cell, B cell, and myeloid cell populations are consistent with sensitivity and resistance. We identified the upregulated expression ofPLA2G2D, an immune-regulating phospholipase, as a potential biomarker of adaptive resistance to ICB. Together, these findings provide insights into the diversity of immunogenomic mechanisms that underpin pembrolizumab outcomes.
Efficient and continuous microwave photoconversion in hybrid cavity-semiconductor nanowire double quantum dot diodes
Authors: Khan Waqar , Potts Patrick P. , Lehmann Sebastian , Thelander Claes , Dick Kimberly A. , Samuelsson Peter , Maisi Ville F. 
Published: August 2021

AbstractConverting incoming photons to electrical current is the key operation principle of optical photodetectors and it enables a host of emerging quantum information technologies. The leading approach for continuous and efficient detection in the optical domain builds on semiconductor photodiodes. However, there is a paucity of efficient and continuous photon detectors in the microwave regime, because photon energies are four to five orders of magnitude lower therein and conventional photodiodes do not have that sensitivity. Here we tackle this gap and demonstrate how microwave photons can be efficiently and continuously converted to electrical current in a high-quality, semiconducting nanowire double quantum dot resonantly coupled to a cavity. In particular, in our photodiode device, an absorbed photon gives rise to a single electron tunneling through the double dot, with a conversion efficiency reaching 6%.
Efficient intracellular delivery of proteins by a multifunctional chimaeric peptide in vitro and in vivo
Authors: Yu Siyuan , Yang Han , Li Tingdong , Pan Haifeng , Ren Shuling , Luo Guoxing , Jiang Jinlu , Yu Linqi , Chen Binbing , Zhang Yali , Wang Shaojuan , Tian Rui , Zhang Tianying , Zhang Shiyin , Chen Yixin , Yuan Quan , Ge Shengxiang , Zhang Jun , Xia Ningshao 
Published: August 2021

AbstractProtein delivery with cell-penetrating peptide is opening up the possibility of using targets inside cells for therapeutic or biological applications; however, cell-penetrating peptide-mediated protein delivery commonly suffers from ineffective endosomal escape and low tolerance in serum, thereby limiting in vivo efficacy. Here, we present an intracellular protein delivery system consisting of four modules in series: cell-penetrating peptide, pH-dependent membrane active peptide, endosome-specific protease sites and a leucine zipper. This system exhibits enhanced delivery efficiency and serum tolerance, depending on proteolytic cleavage-facilitated endosomal escape and leucine zipper-based dimerisation. Intravenous injection of protein phosphatase 1B fused with this system successfully suppresses the tumour necrosis factor-α-induced systemic inflammatory response and acetaminophen-induced acute liver failure in a mouse model. We believe that the strategy of using multifunctional chimaeric peptides is valuable for the development of cell-penetrating peptide-based protein delivery systems, and facilitate the development of biological macromolecular drugs for use against intracellular targets.
Additive manufacturing of strong silica sand structures enabled by polyethyleneimine binder
Authors: Gilmer Dustin B. , Han Lu , Lehmann Michelle L. , Siddel Derek H. , Yang Guang , Chowdhury Azhad U. , Doughty Benjamin , Elliott Amy M. , Saito Tomonori 
Published: August 2021

AbstractBinder Jet Additive Manufacturing (BJAM) is a versatile AM technique that can form parts from a variety of powdered materials including metals, ceramics, and polymers. BJAM utilizes inkjet printing to selectively bind these powder particles together to form complex geometries. Adoption of BJAM has been limited due to its inability to form strong green parts using conventional binders. We report the discovery of a versatile polyethyleneimine (PEI) binder for silica sand that doubled the flexural strength of parts to 6.28 MPa compared with that of the conventional binder, making it stronger than unreinforced concrete (~4.5 MPa) in flexural loading. Furthermore, we demonstrate that PEI in the printed parts can be reacted with ethyl cyanoacrylate through a secondary infiltration, resulting in an increase in flexural strength to 52.7 MPa. The strong printed parts coupled with the ability for sacrificial washout presents potential to revolutionize AM in various applications including construction and tooling.
Epigenetic inactivation of the autophagy–lysosomal system in appendix in Parkinson’s disease
Authors: Gordevicius Juozas , Li Peipei , Marshall Lee L. , Killinger Bryan A. , Lang Sean , Ensink Elizabeth , Kuhn Nathan C. , Cui Wei , Maroof Nazia , Lauria Roberta , Rueb Christina , Siebourg-Polster Juliane , Maliver Pierre , Lamp Jared , Vega Irving , Manfredsson Fredric P. , Britschgi Markus , Labrie Viviane 
Published: August 2021

AbstractThe gastrointestinal tract may be a site of origin for α-synuclein pathology in idiopathic Parkinson’s disease (PD). Disruption of the autophagy-lysosome pathway (ALP) may contribute to α-synuclein aggregation. Here we examined epigenetic alterations in the ALP in the appendix by deep sequencing DNA methylation at 521 ALP genes. We identified aberrant methylation at 928 cytosines affecting 326 ALP genes in the appendix of individuals with PD and widespread hypermethylation that is also seen in the brain of individuals with PD. In mice, we find that DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by α-synuclein pathology. DNA methylation changes at ALP genes induced by synucleinopathy are associated with the ALP abnormalities observed in the appendix of individuals with PD specifically involving lysosomal genes. Our work identifies epigenetic dysregulation of the ALP which may suggest a potential mechanism for accumulation of α-synuclein pathology in idiopathic PD.
Global phylogenomic analyses of Mycobacterium abscessus provide context for non cystic fibrosis infections and the evolution of antibiotic resistance
Authors: Bronson Ryan A. , Gupta Chhavi , Manson Abigail L. , Nguyen Jan A. , Bahadirli-Talbott Asli , Parrish Nicole M. , Earl Ashlee M. , Cohen Keira A. 
Published: August 2021

AbstractMycobacterium abscessus (MAB) is an emerging pathogen that leads to chronic lung infections. To date, the global population structure of non-cystic fibrosis (CF) MAB and evolutionary patterns of drug resistance emergence have not been investigated. Here we construct a global dataset of 1,279 MAB whole genomes from CF or non-CF patients. We utilize whole genome analysis to assess relatedness, phylogeography, and drug resistance evolution. MAB isolates from CF and non-CF hosts are interspersed throughout the phylogeny, such that the majority of dominant circulating clones include isolates from both populations, indicating that global spread of MAB clones is not sequestered to CF contexts. We identify a large clade of M. abscessus harboring the erm(41) T28C mutation, predicted to confer macrolide susceptibility in this otherwise macrolide-resistant species. Identification of multiple evolutionary events within this clade, consistent with regain of wild type, intrinsic macrolide resistance, underscores the critical importance of macrolides in MAB.
SnapHiC: a computational pipeline to identify chromatin loops from single-cell Hi-C data
Authors: Yu Miao , Abnousi Armen , Zhang Yanxiao , Li Guoqiang , Lee Lindsay , Chen Ziyin , Fang Rongxin , Lagler Taylor M. , Yang Yuchen , Wen Jia , Sun Quan , Li Yun , Ren Bing , Hu Ming 
Published: August 2021

AbstractSingle-cell Hi-C (scHi-C) analysis has been increasingly used to map chromatin architecture in diverse tissue contexts, but computational tools to define chromatin loops at high resolution from scHi-C data are still lacking. Here, we describe Single-Nucleus Analysis Pipeline for Hi-C (SnapHiC), a method that can identify chromatin loops at high resolution and accuracy from scHi-C data. Using scHi-C data from 742 mouse embryonic stem cells, we benchmark SnapHiC against a number of computational tools developed for mapping chromatin loops and interactions from bulk Hi-C. We further demonstrate its use by analyzing single-nucleus methyl-3C-seq data from 2,869 human prefrontal cortical cells, which uncovers cell type-specific chromatin loops and predicts putative target genes for noncoding sequence variants associated with neuropsychiatric disorders. Our results indicate that SnapHiC could facilitate the analysis of cell type-specific chromatin architecture and gene regulatory programs in complex tissues.
Novel and disappearing climates in the global surface ocean from 1800 to 2100
Authors: Lotterhos Katie E. , Láruson Áki J. , Jiang Li-Qing 
Published: August 2021

AbstractMarine ecosystems are experiencing unprecedented warming and acidification caused by anthropogenic carbon dioxide. For the global sea surface, we quantified the degree that present climates are disappearing and novel climates (without recent analogs) are emerging, spanning from 1800 through different emission scenarios to 2100. We quantified the sea surface environment based on model estimates of carbonate chemistry and temperature. Between 1800 and 2000, no gridpoints on the ocean surface were estimated to have experienced an extreme degree of global disappearance or novelty. In other words, the majority of environmental shifts since 1800 were not novel, which is consistent with evidence that marine species have been able to track shifting environments via dispersal. However, between 2000 and 2100 under Representative Concentrations Pathway (RCP) 4.5 and 8.5 projections, 10–82% of the surface ocean is estimated to experience an extreme degree of global novelty. Additionally, 35–95% of the surface ocean is estimated to experience an extreme degree of global disappearance. These upward estimates of climate novelty and disappearance are larger than those predicted for terrestrial systems. Without mitigation, many species will face rapidly disappearing or novel climates that cannot be outpaced by dispersal and may require evolutionary adaptation to keep pace.
Changes in copeptin levels before and 3 months after transsphenoidal surgery according to the presence of postoperative central diabetes insipidus
Authors: Kim Yoo Hyung , Kim Yong Hwy , Je Young Soo , Lee Kyoung Ryul , Lim Hwan Sub , Kim Jung Hee 
Published: August 2021

AbstractCopeptin levels reflect arginine vasopressin (AVP) release from the hypothalamus. Pituitary surgery often impairs AVP release and results in central diabetes insipidus (CDI). Here, we aimed to investigate how serum copeptin level changes 3 months after pituitary surgery and whether it has a diagnostic value for postoperative permanent CDI. Consecutive patients who underwent endoscopic transsphenoidal surgery at a single tertiary hospital were recruited. Serum copeptin levels were measured preoperatively and 3 months postoperatively. Among 88 patients, transient and permanent CDI occurred in 17 (19.3%) and 23 (26.1%), respectively. Three-month postoperative copeptin levels significantly declined from preoperative levels in permanent CDI group (P < 0.001, percentage difference =  − 42.2%) and also in the transient CDI group (P = 0.002, − 27.2%). Three months postoperative copeptin level < 1.9 pmol/L under normal serum sodium levels was the optimal cutoff value for diagnosing permanent CDI with an accuracy of 81.8%, while 3-month postoperative copeptin level ≥ 3.5 pmol/L excluded the CDI with a negative predictive value of 100%. Conclusively, 3 months postoperative copeptin levels significantly decreased from preoperative levels in the transient CDI group as well as the permanent CDI group. Three-month postoperative copeptin levels ≥ 3.5 pmol/L under normal serum sodium levels may be diagnostic for excluding postoperative CDI.
A prospective cohort study on longitudinal trajectories of cognitive function after stroke
Authors: Buvarp Dongni , Rafsten Lena , Abzhandadze Tamar , Sunnerhagen Katharina S. 
Published: August 2021

AbstractThe study aimed to determine longitudinal trajectories of cognitive function during the first year after stroke. The Montreal Cognitive Assessment (MoCA) was used to screen cognitive function at 36–48 h, 3-months, and 12-months post-stroke. Individuals who shared similar trajectories were classified by applying the group-based trajectory models. Data from 94 patients were included in the analysis. Three cognitive functioning groups were identified by the trajectory models: high [14 patients (15%)], medium [58 (62%)] and low [22 (23%)]. For the high and medium groups, cognitive function improved at 12 months, but this did not occur in the low group. After age, sex and education matching to the normative MoCA from the Swedish population, 52 patients (55%) were found to be cognitively impaired at baseline, and few patients had recovered at 12 months. The impact on memory differs between cognitive functioning groups, whereas the impact on activities of daily living was not different. Patients with the poorest cognitive function did not improve at one-year poststroke and were prone to severe memory problems. These findings may help to increase focus on long-term rehabilitation plans for those patients, and more accurately assess their needs and difficulties experienced in daily living.