bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the Chicxulub Impact Stratigraphy and Peak Ring Using Drilling and Seismic Data
Authors: Christeson G. L. , Morgan J. V. , Gulick S. P. S. 
Published: August 2021

AbstractWe integrate high‐resolution full‐waveform velocity models with seismic reflection images to map the peak ring and impactite stratigraphy at the Chicxulub structure. International Ocean Discovery Program/International Continental scientific Drilling Program Site M0077 provides ground truth for our interpretations. The peak ring is narrower (∼10 km width) where it is high relief (600–700 m below seafloor) and wider (∼15 km width) where it is lower relief (1,000–1,200 m below seafloor). Both target asymmetry and angle of impact could have contributed to observed differences in peak ring morphology. We interpret a layer of lowered velocities as a resurge layer formed from the ocean resurge, seiche, and returning tsunami flowing into the newly formed impact basin. This graded suevite layer has an average thickness of 187 ± 58 m with only local thickness differences within the annular trough, peak ring, and central basin. These observations suggest that the returning ocean was of substantial height and energetic enough to carry debris across the entire topographic peak ring. We map impact melt rock throughout the crater, with a thick impact melt sheet in the central basin (>500 m), thin intermittent melt rock capping the peak ring, and a ∼500‐m thick layer of melt rock in the annular trough near the peak ring that thins toward the crater rim. We estimate that ∼70%–75% of the melt rock volume is in the central basin. We image features above and adjacent to the central basin melt sheet that we interpret as upflow zones associated with a long‐lasting hydrothermal system.
Blockage Probability Modeling of Large Wood at Reservoir Spillways With Piers
Authors: Furlan Paloma , Pfister Michael , Matos Jorge , Amado Conceição , Schleiss Anton J. 
Published: August 2021

AbstractLarge wood increases the morphological and hydraulic complexity of rivers, yet it may block and modify the flood discharge capacity of hydraulic structures. To assess the related risk, blockage probability estimation for hydraulic structures such as reservoir spillways is needed. This work presents unstudied parameters for blockage of large wood with a reservoir‐type approach flow, where the inflow velocity has a negligible magnitude. Experiments were conducted in a channel with an ogee crested spillway equipped with piers, representing a commonly used hydraulic structure. Artificial stems were used to systematically evaluate the influence of stem length and stem draft on the blocking process. Different hydraulic conditions were evaluated by changing the water level in the reservoir. The head at the spillway crest with respect to stem draft was found to be a key parameter for blockage probability estimation at a spillway. Additionally, stem length was related to the bay width in the estimation of blockage. Larger heads tend to reduce the blocking probability of large wood, for a given stem draft, while increasing the relative stem length tends to increase the blocking probability. A logistic regression model is provided to estimate large wood blockage probability at ogee crested spillways with piers. Finally, recommendations for engineering practice are presented.
Advances of surface-enhanced Raman and IR spectroscopies: from nano/microstructures to macro-optical design
Authors: Wang Hai-Long , You En-Ming , Panneerselvam Rajapandiyan , Ding Song-Yuan , Tian Zhong-Qun 
Published: August 2021

AbstractRaman and infrared (IR) spectroscopy are powerful analytical techniques, but have intrinsically low detection sensitivity. There have been three major steps (i) to advance the optical system of the light excitation, collection, and detection since 1920s, (ii) to utilize nanostructure-based surface-enhanced Raman scattering (SERS) and surface-enhanced infrared absorption (SEIRA) since 1990s, and (iii) to rationally couple (i) and (ii) for maximizing the total detection sensitivity since 2010s. After surveying the history of SERS and SEIRA, we outline the principle of plasmonics and the different mechanisms of SERS and SEIRA. We describe various interactions of light with nano/microstructures, localized surface plasmon, surface plasmon polariton, and lightning-rod effect. Their coupling effects can significantly increase the surface sensitivity by designing nanoparticle–nanoparticle and nanoparticle–substrate configuration. As the nano/microstructures have specific optical near-field and far-field behaviors, we focus on how to systematically design the macro-optical systems to maximize the excitation efficiency and detection sensitivity. We enumerate the key optical designs in particular ATR-based operation modes of directional excitation and emission from visible to IR spectral region. We also present some latest advancements on scanning-probe microscopy-based nanoscale spectroscopy. Finally, prospects and further developments of this field are given with emphasis on emerging techniques and methodologies.
Pattern recognition receptors in health and diseases
Authors: Li Danyang , Wu Minghua 
Published: August 2021

AbstractPattern recognition receptors (PRRs) are a class of receptors that can directly recognize the specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce nonspecific anti-infection, antitumor, and other immunoprotective effects. Most PRRs in the innate immune system of vertebrates can be classified into the following five types based on protein domain homology: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs), and absent in melanoma-2 (AIM2)-like receptors (ALRs). PRRs are basically composed of ligand recognition domains, intermediate domains, and effector domains. PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains, initiating downstream signaling pathways to exert effects. In recent years, the increased researches on the recognition and binding of PRRs and their ligands have greatly promoted the understanding of different PRRs signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors. This review describes in detail the history, the structural characteristics, ligand recognition mechanism, the signaling pathway, the related disease, new drugs in clinical trials and clinical therapy of different types of PRRs, and discusses the significance of the research on pattern recognition mechanism for the treatment of PRR-related diseases.
Antidepressant side effects and their impact on treatment outcome in people with major depressive disorder: an iSPOT-D report
Authors: Braund Taylor A. , Tillman Gabriel , Palmer Donna M. , Gordon Evian , Rush A. John , Harris Anthony W. F. 
Published: August 2021

AbstractSide effects to antidepressant medications are common and can impact the prognosis of successful treatment outcome in people with major depressive disorder (MDD). However, few studies have investigated the severity of side effects over the course of treatment and their association with treatment outcome. Here we assessed the severity of side effects and the impact of treatment type and anxiety symptoms over the course of treatment, as well as whether side effects were associated with treatment outcome. Participants were N = 1008 adults with a current diagnosis of single-episode or recurrent, nonpsychotic MDD. Participants were randomised to receive escitalopram, sertraline, or venlafaxine-extended release with equal probability and reassessed at 8 weeks regarding Hamilton Rating Scale Depression (HRSD17) and Quick Inventory of Depressive Symptomatology (QIDS-SR16) remission and response. Severity of side effects were assessed using the Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale and assessed at day 4 and weeks 2, 4, 6, and 8. Frequency, intensity, and burden of side effects were greatest at week 2, then only frequency and intensity of side effects gradually decreased up to week 6. Treatment type and anxiety symptoms did not impact the severity of side effects. A greater burden—but not frequency or intensity—of side effects was associated with poorer treatment outcome and as early as 4 days post-treatment. Together, this work provides an informative mapping of the progression of side effects throughout the treatment course and their association with treatment outcome. Importantly, the burden of side effects that are present as early as 4 days post-treatment predicts poorer treatment outcome and should be monitored closely. iSPOT-D: Registry name: ClinicalTrials.gov. Registration number: NCT00693849.
COVID-19 restrictions and age-specific mental health—U.S. probability-based panel evidence
Authors: Sojli Elvira , Tham Wing Wah , Bryant Richard , McAleer Michael 
Published: August 2021

AbstractSocial distancing, self-isolation, quarantining, and lockdowns arising from the COVID-19 pandemic have been common restrictions as governments have attempted to limit the rapid virus transmission. In this study, we identified drivers of adverse mental and behavioral health during the COVID-19 pandemic and whether factors such as social isolation and various restrictions serve as additional stressors for different age groups. Univariate and multivariate regression analyses were conducted on a unique dataset based on a national probability-based survey dedicated to understanding the impact of COVID-19 in the U.S., which includes 19 questions on the individual impact of restrictions, bans, and closures. The analysis used a moderate distress scale built on five questions related to mental health for 3,646 respondents. The mental health of young adults (18−34 years old) was the most affected by restrictions, while that of older adults (>55 years old) was less affected. In addition, demographic and health characteristics associated with differences in mental health varied by age group. The findings in this analysis highlight the differential mental health needs of different age groups and point to the marked necessity for differentiated and targeted responses to the mental health effects of COVID-19 by age group.
Porous functionalized polymers enable generating and transporting hyperpolarized mixtures of metabolites
Authors: El Daraï Théo , Cousin Samuel F. , Stern Quentin , Ceillier Morgan , Kempf James , Eshchenko Dmitry , Melzi Roberto , Schnell Marc , Gremillard Laurent , Bornet Aurélien , Milani Jonas , Vuichoud Basile , Cala Olivier , Montarnal Damien , Jannin Sami 
Published: August 2021

AbstractHyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show the synthesis of hyperpolarizing polymers (HYPOPs) that can generate radical- and contaminant-free hyperpolarized samples within minutes with lifetimes exceeding hours in the solid state. HYPOPs feature tunable macroporous porosity, with porous volumes up to 80% and concentration of nitroxide radicals grafted in the bulk matrix up to 285 μmol g−1. Analytes can be efficiently impregnated as aqueous/alcoholic solutions and hyperpolarized up to P(13C) = 25% within 8 min, through the combination of 1H spin diffusion and 1H → 13C cross polarization. Solutions of 13C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state 13C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances.
GIANA allows computationally-efficient TCR clustering and multi-disease repertoire classification by isometric transformation
Authors: Zhang Hongyi , Zhan Xiaowei , Li Bo 
Published: August 2021

AbstractSimilarity in T-cell receptor (TCR) sequences implies shared antigen specificity between receptors, and could be used to discover novel therapeutic targets. However, existing methods that cluster T-cell receptor sequences by similarity are computationally inefficient, making them impractical to use on the ever-expanding datasets of the immune repertoire. Here, we developed GIANA (Geometric Isometry-based TCR AligNment Algorithm) a computationally efficient tool for this task that provides the same level of clustering specificity as TCRdist at 600 times its speed, and without sacrificing accuracy. GIANA also allows the rapid query of large reference cohorts within minutes. Using GIANA to cluster large-scale TCR datasets provides candidate disease-specific receptors, and provides a new solution to repertoire classification. Querying unseen TCR-seq samples against an existing reference differentiates samples from patients across various cohorts associated with cancer, infectious and autoimmune disease. Our results demonstrate how GIANA could be used as the basis for a TCR-based non-invasive multi-disease diagnostic platform.
Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia
Authors: Don-Doncow Nicholas , Vanherle Lotte , Matthes Frank , Petersen Sine Kragh , Matuskova Hana , Rattik Sara , Härtlova Anetta , Meissner Anja 
Published: August 2021

AbstractEvidence associates cardiovascular risk factors with unfavorable systemic and neuro-inflammation and cognitive decline in the elderly. Cardiovascular therapeutics (e.g., statins and anti-hypertensives) possess immune-modulatory functions in parallel to their cholesterol- or blood pressure (BP)-lowering properties. How their ability to modify immune responses affects cognitive function is unknown. Here, we examined the effect of chronic hypercholesterolemia on inflammation and memory function in Apolipoprotein E (ApoE) knockout mice and normocholesterolemic wild-type mice. Chronic hypercholesterolemia that was accompanied by moderate blood pressure elevations associated with apparent immune system activation characterized by increases in circulating pro-inflammatory Ly6Chi monocytes in ApoE-/- mice. The persistent low-grade immune activation that is associated with chronic hypercholesterolemia facilitates the infiltration of pro-inflammatory Ly6Chi monocytes into the brain of aged ApoE-/- but not wild-type mice, and links to memory dysfunction. Therapeutic cholesterol-lowering through simvastatin reduced systemic and neuro-inflammation, and the occurrence of memory deficits in aged ApoE-/- mice with chronic hypercholesterolemia. BP-lowering therapy alone (i.e., hydralazine) attenuated some neuro-inflammatory signatures but not the occurrence of memory deficits. Our study suggests a link between chronic hypercholesterolemia, myeloid cell activation and neuro-inflammation with memory impairment and encourages cholesterol-lowering therapy as safe strategy to control hypercholesterolemia-associated memory decline during ageing.
The role of Psl in the failure to eradicate Pseudomonas aeruginosa biofilms in children with cystic fibrosis
Authors: Morris Amanda J. , Jackson Lindsay , CW Yau Yvonne , Reichhardt Courtney , Beaudoin Trevor , Uwumarenogie Stephanie , Guttman Kevin M. , Lynne Howell P. , Parsek Matthew R. , Hoffman Lucas R. , Nguyen Dao , DiGiandomenico Antonio , Guttman David S. , Wozniak Daniel J. , Waters Valerie J. 
Published: August 2021

AbstractThe exopolysaccharide Psl contributes to biofilm structure and antibiotic tolerance and may play a role in the failure to eradicate Pseudomonas aeruginosa from cystic fibrosis (CF) airways. The study objective was to determine whether there were any differences in Psl in P. aeruginosa isolates that were successfully eradicated compared to those that persisted, despite inhaled tobramycin treatment, in children with CF. Initial P. aeruginosa isolates were collected from children with CF undergoing eradication treatment, grown as biofilms and labeled with 3 anti-Psl monoclonal antibodies (Cam003/Psl0096, WapR001, WapR016) before confocal microscopy visualization. When grown as biofilms, P. aeruginosa isolates from children who failed antibiotic eradication therapy, had significantly increased Psl0096 binding compared to isolates from those who cleared P. aeruginosa. This was confirmed in P. aeruginosa isolates from the SickKids Eradication Cohort as well as the Early Pseudomonas Infection Control (EPIC) trial. Increased anti-Psl antibody binding was associated with bacterial aggregation and tobramycin tolerance. The biofilm matrix represents a potential therapeutic target to improve P. aeruginosa eradication treatment.
Phase 1b clinical trial of ado-trastuzumab emtansine and ribociclib for HER2-positive metastatic breast cancer
Authors: Spring Laura M. , Clark Shealagh L. , Li Tianyu , Goel Shom , Tayob Nabihah , Viscosi Elene , Abraham Elizabeth , Juric Dejan , Isakoff Steven J. , Mayer Erica , Moy Beverly , Supko Jeffrey G. , Tolaney Sara M. , Bardia Aditya 
Published: August 2021

AbstractPatients with HER2+ metastatic breast cancer are often treated with a multitude of therapies in the metastatic setting, and additional strategies to prolong responses to anti-HER2 therapies are needed. Preclinical evidence suggests synergy between cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors and anti-HER2 therapies. We conducted a phase 1b study of ribociclib and ado-trastuzumab emtansine (T-DM1) in patients with advanced/metastatic HER2-positive breast cancer previously treated with trastuzumab and a taxane in any setting, with four or fewer prior lines of therapy in the metastatic setting. A standard 3 + 3 dose-escalation design was used to evaluate various doses of ribociclib in combination with T-DM1, starting at 300 mg. The primary objective was to determine the maximum tolerated dose and/or recommended phase 2 dose (RP2D) of ribociclib in combination with T-DM1. A total of 12 patients were enrolled. During dose-escalation, patients received doses of ribociclib of 300 mg (n = 3), 400 mg (n = 3), 500 mg (n = 3), and 600 mg (n = 3). No dose-limiting toxicities were observed. The majority of toxicities were Grade 1 and 2, and the most common Grade 3 toxicities were neutropenia (33%), leukopenia (33%), and anemia (25%). After a median follow-up of 12.4 months, the median PFS was 10.4 months (95% confidence interval, 2.7–19.3). Based on the pharmacokinetic analysis, adverse events, and dose reductions, 400 mg was determined to be the RP2D for ribociclib given on days 8–21 of a 21-day cycle with T-DM1.
A phononic interface between a superconducting quantum processor and quantum networked spin memories
Authors: Neuman Tomáš , Eichenfield Matt , Trusheim Matthew E. , Hackett Lisa , Narang Prineha , Englund Dirk 
Published: August 2021

AbstractWe introduce a method for high-fidelity quantum state transduction between a superconducting microwave qubit and the ground state spin system of a solid-state artificial atom, mediated via an acoustic bus connected by piezoelectric transducers. Applied to present-day experimental parameters for superconducting circuit qubits and diamond silicon-vacancy centers in an optimized phononic cavity, we estimate quantum state transduction with fidelity exceeding 99% at a MHz-scale bandwidth. By combining the complementary strengths of superconducting circuit quantum computing and artificial atoms, the hybrid architecture provides high-fidelity qubit gates with long-lived quantum memory, high-fidelity measurement, large qubit number, reconfigurable qubit connectivity, and high-fidelity state and gate teleportation through optical quantum networks.
Fully automated closed-loop glucose control compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis: an open-label, randomized crossover trial
Authors: Boughton Charlotte K. , Tripyla Afroditi , Hartnell Sara , Daly Aideen , Herzig David , Wilinska Malgorzata E. , Czerlau Cecilia , Fry Andrew , Bally Lia , Hovorka Roman 
Published: August 2021

AbstractWe evaluated the safety and efficacy of fully closed-loop insulin therapy compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis. In an open-label, multinational, two-center, randomized crossover trial, 26 adults with type 2 diabetes requiring dialysis (17 men, 9 women, average age 68 ± 11 years (mean ± s.d.), diabetes duration of 20 ± 10 years) underwent two 20-day periods of unrestricted living, comparing the Cambridge fully closed-loop system using faster insulin aspart (‘closed-loop’) with standard insulin therapy and a masked continuous glucose monitor (‘control’) in random order. The primary endpoint was time in target glucose range (5.6–10.0 mmol l−1). Thirteen participants received closed-loop first and thirteen received control therapy first. The proportion of time in target glucose range (5.6–10.0 mmol l−1; primary endpoint) was 52.8 ± 12.5% with closed-loop versus 37.7 ± 20.5% with control; mean difference, 15.1 percentage points (95% CI 8.0–22.2;P < 0.001). Mean glucose was lower with closed-loop than control (10.1 ± 1.3 versus 11.6 ± 2.8 mmol l−1;P = 0.003). Time in hypoglycemia (<3.9 mmol l−1) was reduced with closed-loop versus control (median (IQR) 0.1 (0.0–0.4%) versus 0.2 (0.0–0.9%);P = 0.040). No severe hypoglycemia events occurred during the control period, whereas one severe hypoglycemic event occurred during the closed-loop period, but not during closed-loop operation. Fully closed-loop improved glucose control and reduced hypoglycemia compared with standard insulin therapy in adult outpatients with type 2 diabetes requiring dialysis. The trial registration number is NCT04025775.
Transcriptional landscape of cellular networks reveal interactions driving the dormancy mechanisms in cancer
Authors: Uzuner Dilara , Akkoç Yunus , Peker Nesibe , Pir Pınar , Gözüaçık Devrim , Çakır Tunahan 
Published: August 2021

AbstractPrimary cancer cells exert unique capacity to disseminate and nestle in distant organs. Once seeded in secondary sites, cancer cells may enter a dormant state, becoming resistant to current treatment approaches, and they remain silent until they reactivate and cause overt metastases. To illuminate the complex mechanisms of cancer dormancy, 10 transcriptomic datasets from the literature enabling 21 dormancy–cancer comparisons were mapped on protein–protein interaction networks and gene-regulatory networks to extract subnetworks that are enriched in significantly deregulated genes. The genes appearing in the subnetworks and significantly upregulated in dormancy with respect to proliferative state were scored and filtered across all comparisons, leading to a dormancy–interaction network for the first time in the literature, which includes 139 genes and 1974 interactions. The dormancy interaction network will contribute to the elucidation of cellular mechanisms orchestrating cancer dormancy, paving the way for improvements in the diagnosis and treatment of metastatic cancer.