bluuebunny/crossref_metadata_2025 huggingface dataset:
The Convective‐To‐Total Precipitation Ratio and the “Drizzling” Bias in Climate Models
Authors: Chen Di , Dai Aiguo , Hall Alex
Published: August 2021

Overestimation of precipitation frequency and duration while underestimating intensity, that is, the “drizzling” bias, has been a long‐standing problem of global climate models. Here we explore this issue from the perspective of precipitation partitioning. We found that most models in the Climate Model Intercomparison Project Phase 5 (CMIP5) have high convective‐to‐total precipitation (PC/PR) ratios in low latitudes. Convective precipitation has higher frequency and longer duration but lower intensity than non‐convective precipitation in many models. As a result, the high PC/PR ratio contributes to the “drizzling” bias over low latitudes. The PC/PR ratio and associated “drizzling” bias increase as model resolution coarsens from 0.5° to 2.0°, but the resolution's effect weakens as the grid spacing increases from 2.0° to 3.0°. Some of the CMIP6 models show reduced “drizzling” bias associated with decreased PC/PR ratio. Thus, more reasonable precipitation partitioning, along with finer model resolution should alleviate the “drizzling” bias within current climate models.
Characterization and Evolution of Organized Shallow Convection in the Downstream North Atlantic Trades
Authors: Schulz Hauke , Eastman Ryan , Stevens Bjorn
Published: August 2021

Four previously identified patterns of meso‐scale cloud organization in the trades — called Sugar, Gravel, Flowers, and Fish — are studied using long‐term records of ground‐based measurements, satellite observations and reanalyzes. A deep neural network trained to detect these patterns is applied to satellite imagery to identify periods during which a particular pattern is observed over the Barbados Cloud Observatory. Surface‐based remote sensing at the observatory is composited and shows that the patterns can be distinguished by differences in cloud geometry. Variations in total cloudiness among the patterns are dominated by variations in cloud‐top cloudiness. Cloud amount near cloud base varies little. Each pattern is associated with a distinct atmospheric environment whose characteristics are traced back to origins that are not solely within the trades. Sugar air‐masses are characterized by weak winds and of tropical origin. Fish are driven by convergence lines originating from synoptical disturbances. Gravel and Flowers are most native to the trades, but distinguish themselves with slightly stronger winds and stronger subsidence in the first case and greater stability in the latter. The patterns with the higher cloud amounts and more negative cloud‐radiative effects, Flowers and Fish, are selected by conditions expected to occur less frequently with greenhouse warming.
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

We 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

Large 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

Raman 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

Pattern 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

Side 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

Social 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

Hyperpolarization 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

Similarity 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

Evidence 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

The 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

Patients 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

We 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

We 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

Primary 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.
Hepatic cell mobilization for protection against ischemic myocardial injury
Authors: Liu Shu Q. , Troy John B. , Luan Chi-Hao , Guillory Roger J.
Published: August 2021

The heart is capable of activating protective mechanisms in response to ischemic injury to support myocardial survival and performance. These mechanisms have been recognized primarily in the ischemic heart, involving paracrine signaling processes. Here, we report a distant cardioprotective mechanism involving hepatic cell mobilization to the ischemic myocardium in response to experimental myocardial ischemia–reperfusion (MI-R) injury. A parabiotic mouse model was generated by surgical skin-union of two mice and used to induce bilateral MI-R injury with unilateral hepatectomy, establishing concurrent gain- and loss-of-hepatic cell mobilization conditions. Hepatic cells, identified based on the cell-specific expression of enhanced YFP, were found in the ischemic myocardium of parabiotic mice with intact liver (0.2 ± 0.1%, 1.1 ± 0.3%, 2.7 ± 0.6, and 0.7 ± 0.4% at 1, 3, 5, and 10 days, respectively, in reference to the total cell nuclei), but not significantly in the ischemic myocardium of parabiotic mice with hepatectomy (0 ± 0%, 0.1 ± 0.1%, 0.3 ± 0.2%, and 0.08 ± 0.08% at the same time points). The mobilized hepatic cells were able to express and release trefoil factor 3 (TFF3), a protein mitigating MI-R injury as demonstrated in TFF3−/− mice (myocardium infarcts 17.6 ± 2.3%, 20.7 ± 2.6%, and 15.3 ± 3.8% at 1, 5, and 10 days, respectively) in reference to wildtype mice (11.7 ± 1.9%, 13.8 ± 2.3%, and 11.0 ± 1.8% at the same time points). These observations suggest that MI-R injury can induce hepatic cell mobilization to support myocardial survival by releasing TFF3.
Ecological plasticity to ions concentration determines genetic response and dominance of Anopheles coluzzii larvae in urban coastal habitats of Central Africa
Authors: Longo-Pendy Neil M. , Tene-Fossog Billy , Tawedi Robert E. , Akone-Ella Ousman , Toty Celine , Rahola Nil , Braun Jean-Jacques , Berthet Nicolas , Kengne Pierre , Costantini Carlo , Ayala Diego
Published: August 2021

In Central Africa, the malaria vectorAnopheles coluzziiis predominant in urban and coastal habitats. However, little is known about the environmental factors that may be involved in this process. Here, we performed an analysis of 28 physicochemical characteristics of 59 breeding sites across 5 urban and rural sites in coastal areas of Central Africa. We then modelled the relative frequency ofAn. coluzziilarvae to these physicochemical parameters in order to investigate environmental patterns. Then, we assessed the expression variation of 10 candidate genes inAn. coluzzii, previously incriminated with insecticide resistance and osmoregulation in urban settings. Our results confirmed the ecological plasticity ofAn. coluzziilarvae to breed in a large range of aquatic conditions and its predominance in breeding sites rich in ions. Gene expression patterns were comparable between urban and rural habitats, suggesting a broad response to ions concentrations of whatever origin. Altogether,An. coluzziiexhibits a plastic response to occupy both coastal and urban habitats. This entails important consequences for malaria control in the context of the rapid urban expansion in Africa in the coming years.
Lung nodule detection in chest X-rays using synthetic ground-truth data comparing CNN-based diagnosis to human performance
Authors: Schultheiss Manuel , Schmette Philipp , Bodden Jannis , Aichele Juliane , Müller-Leisse Christina , Gassert Felix G. , Gassert Florian T. , Gawlitza Joshua F. , Hofmann Felix C. , Sasse Daniel , von Schacky Claudio E. , Ziegelmayer Sebastian , De Marco Fabio , Renger Bernhard , Makowski Marcus R. , Pfeiffer Franz , Pfeiffer Daniela
Published: August 2021

We present a method to generate synthetic thorax radiographs with realistic nodules from CT scans, and a perfect ground truth knowledge. We evaluated the detection performance of nine radiologists and two convolutional neural networks in a reader study. Nodules were artificially inserted into the lung of a CT volume and synthetic radiographs were obtained by forward-projecting the volume. Hence, our framework allowed for a detailed evaluation of CAD systems’ and radiologists’ performance due to the availability of accurate ground-truth labels for nodules from synthetic data. Radiographs for network training (U-Net and RetinaNet) were generated from 855 CT scans of a public dataset. For the reader study, 201 radiographs were generated from 21 nodule-free CT scans with altering nodule positions, sizes and nodule counts of inserted nodules. Average true positive detections by nine radiologists were 248.8 nodules, 51.7 false positive predicted nodules and 121.2 false negative predicted nodules. The best performing CAD system achieved 268 true positives, 66 false positives and 102 false negatives. Corresponding weighted alternative free response operating characteristic figure-of-merits (wAFROC FOM) for the radiologists range from 0.54 to 0.87 compared to a value of 0.81 (CI 0.75–0.87) for the best performing CNN. The CNN did not perform significantly better against the combined average of the 9 readers (p = 0.49). Paramediastinal nodules accounted for most false positive and false negative detections by readers, which can be explained by the presence of more tissue in this area.
High-throughput spatial sensitive quantitative phase microscopy using low spatial and high temporal coherent illumination
Authors: Ahmad Azeem , Dubey Vishesh , Jayakumar Nikhil , Habib Anowarul , Butola Ankit , Nystad Mona , Acharya Ganesh , Basnet Purusotam , Mehta Dalip Singh , Ahluwalia Balpreet Singh
Published: August 2021

High space-bandwidth product with high spatial phase sensitivity is indispensable for a single-shot quantitative phase microscopy (QPM) system. It opens avenue for widespread applications of QPM in the field of biomedical imaging. Temporally low coherence light sources are implemented to achieve high spatial phase sensitivity in QPM at the cost of either reduced temporal resolution or smaller field of view (FOV). In addition, such light sources have low photon degeneracy. On the contrary, high temporal coherence light sources like lasers are capable of exploiting the full FOV of the QPM systems at the expense of less spatial phase sensitivity. In the present work, we demonstrated that use of narrowband partially spatially coherent light source also called pseudo-thermal light source (PTLS) in QPM overcomes the limitations of conventional light sources. The performance of PTLS is compared with conventional light sources in terms of space bandwidth product, phase sensitivity and optical imaging quality. The capabilities of PTLS are demonstrated on both amplitude (USAF resolution chart) and phase (thin optical waveguide, height ~ 8 nm) objects. The spatial phase sensitivity of QPM using PTLS is measured to be equivalent to that for white light source and supports the FOV (18 times more) equivalent to that of laser light source. The high-speed capabilities of PTLS based QPM is demonstrated by imaging live sperm cells that is limited by the camera speed and large FOV is demonstrated by imaging histopathology human placenta tissue samples. Minimal invasive, high-throughput, spatially sensitive and single-shot QPM based on PTLS will enable wider penetration of QPM in life sciences and clinical applications.
Delineating virulence of Vibrio campbellii: a predominant luminescent bacterial pathogen in Indian shrimp hatcheries
Authors: Kumar Sujeet , Kumar Chandra Bhushan , Rajendran Vidya , Abishaw Nishawlini , Anand P. S. Shyne , Kannapan S. , Nagaleekar Viswas K. , Vijayan K. K. , Alavandi S. V.
Published: August 2021

Luminescent vibriosis is a major bacterial disease in shrimp hatcheries and causes up to 100% mortality in larval stages of penaeid shrimps. We investigated the virulence factors and genetic identity of 29 luminescentVibrioisolates from Indian shrimp hatcheries and farms, which were earlier presumed asVibrio harveyi. Haemolysin gene-based species-specific multiplex PCR and phylogenetic analysis ofrpoDandtoxRidentified all the isolates asV. campbellii. The gene-specific PCR revealed the presence of virulence markers involved in quorum sensing (luxM,luxS, cqsA), motility (flaA,lafA), toxin (hly, chiA, serine protease, metalloprotease), and virulence regulators (toxR, luxR) in all the isolates. The deduced amino acid sequence analysis of virulence regulator ToxR suggested four variants, namely A123Q150 (AQ; 18.9%), P123Q150 (PQ; 54.1%), A123P150 (AP; 21.6%), and P123P150 (PP; 5.4% isolates) based on amino acid at 123rd (proline or alanine) and 150th (glutamine or proline) positions. A significantly higher level of the quorum-sensing signal, autoinducer-2 (AI-2, p = 2.2e−12), and significantly reduced protease activity (p = 1.6e−07) were recorded in AP variant, whereas an inverse trend was noticed in the Q150 variants AQ and PQ. The pathogenicity study inPenaeus(Litopenaeus)vannameijuveniles revealed that all the isolates of AQ were highly pathogenic with Cox proportional hazard ratio 15.1 to 32.4 compared to P150 variants; PP (5.4 to 6.3) or AP (7.3 to 14). The correlation matrix suggested that protease, a metalloprotease, was positively correlated with pathogenicity (p > 0.05) and negatively correlated (p < 0.05) with AI-2 and AI-1. The syntenic organization oftoxS-toxR-htpGoperon inV. campbelliiwas found to be similar to pathogenicV. choleraesuggesting a similar regulatory role. The present study emphasizes thatV. campbelliiis a predominant pathogen in Indian shrimp hatcheries, and ToxR plays a significant role as a virulence regulator in the quorum sensing—protease pathway. Further, the study suggests that the presence of glutamine at 150th position (Q150) in ToxR is crucial for the pathogenicity ofV. campbellii.
Co-culture model of B-cell acute lymphoblastic leukemia recapitulates a transcription signature of chemotherapy-refractory minimal residual disease
Authors: Rellick Stephanie L. , Hu Gangqing , Piktel Debra , Martin Karen H. , Geldenhuys Werner J. , Nair Rajesh R. , Gibson Laura F.
Published: August 2021

B-cell acute lymphoblastic leukemia (ALL) is characterized by accumulation of immature hematopoietic cells in the bone marrow, a well-established sanctuary site for leukemic cell survival during treatment. While standard of care treatment results in remission in most patients, a small population of patients will relapse, due to the presence of minimal residual disease (MRD) consisting of dormant, chemotherapy-resistant tumor cells. To interrogate this clinically relevant population of treatment refractory cells, we developed an in vitro cell model in which human ALL cells are grown in co-culture with human derived bone marrow stromal cells or osteoblasts. Within this co-culture, tumor cells are found in suspension, lightly attached to the top of the adherent cells, or buried under the adherent cells in a population that is phase dim (PD) by light microscopy. PD cells are dormant and chemotherapy-resistant, consistent with the population of cells that underlies MRD. In the current study, we characterized the transcriptional signature of PD cells by RNA-Seq, and these data were compared to a published expression data set derived from human MRD B-cell ALL patients. Our comparative analyses revealed that the PD cell population is markedly similar to the MRD expression patterns from the primary cells isolated from patients. We further identified genes and key signaling pathways that are common between the PD tumor cells from co-culture and patient derived MRD cells as potential therapeutic targets for future studies.
Evaluating the energetics of entrainment in a human–machine coupled oscillator system
Authors: Schroeder Ryan T. , Croft James L. , Bertram John E. A.
Published: August 2021

During locomotion, humans sometimes entrain (i.e. synchronize) their steps to external oscillations: e.g. swaying bridges, tandem walking, bouncy harnesses, vibrating treadmills, exoskeletons. Previous studies have discussed the role of nonlinear oscillators (e.g. central pattern generators) in facilitating entrainment. However, the energetics of such interactions are unknown. Given substantial evidence that humans prioritize economy during locomotion, we tested whether reduced metabolic expenditure is associated with human entrainment to vertical force oscillations, where frequency and amplitude were prescribed via a custom mechatronics system during walking. Although metabolic cost was not significantly reduced during entrainment, individuals expended less energy when the oscillation forces did net positive work on the body and roughly selected phase relationships that maximize positive work. It is possible that individuals use mechanical cues to infer energy cost and inform effective gait strategies. If so, an accurate prediction may rely on the relative stability of interactions with the environment. Our results suggest that entrainment occurs over a wide range of oscillation parameters, though not as a direct priority for minimizing metabolic cost. Instead, entrainment may act to stabilize interactions with the environment, thus increasing predictability for the effective implementation of internal models that guide energy minimization.
Higher senescence associated secretory phenotype and lower defense mediator in urinary extracellular vesicles of elders with and without Parkinson disease
Authors: Yeh Shu-hui , Lin Chia-Hsueh , Yang Yun-Jung , Lin Li-Wei , Tseng Chih-Wen , Yang Kuender D.
Published: August 2021

Youth fountain and aging culprits are usually sought and identified in blood but not urine. Extracellular vesicles (EVs) possess parental cell properties, circulate in blood, CSF and urine, and provide paracrine and remote cell–cell communication messengers. This study investigated whether senescence‐associated secretory phenotype (SASP) and immune defense factors in EVs of urine could serve as biomarkers in elderly individuals with and without a comorbidity. Urine samples from young adults and elderly individuals with and without Parkinson disease (PD) were collected and stored at − 80 °C until studies. Urine EVs were separated from a drop-through solution and confirmed by verifying CD9, CD63, CD81 and syntenin expression. The EVs and drop-through solution were subjected to measurement of SASP cytokines and defense factors by Milliplex array assays. Many SASP cytokines and defense factors could be detected in urinary EVs but not urinary solutions. Elderly individuals (age > 60) had significantly higher levels of the SASP-associated factors IL-8, IP-10, GRO, and MCP-1 in EVs (p < 0.05). In contrast, some defense factors, IL-4, MDC and IFNα2 in EVs had significantly lower levels in elderly adults than in young adults (age < 30). Patients with and without PD exhibited a similar SASP profile in EVs but significantly lower levels of IL-10 in the EVs from patients with PD. This study used a simple device to separate urinary EVs from solution for comparisons of SASP and defense mediators between young adults and elders with and without PD. Results from this study indicate that aging signature is present in EVs circulating to urine and the signatures include higher inflammatory mediators and lower defense factors in urinary EVs but not solutions, suggesting a simple method to separate urinary EVs from solutions for searching aging mechanistic biomarkers may make prediction of aging and monitoring of anti-senolytic interventions possible.
Deep graph neural network-based prediction of acute suicidal ideation in young adults
Authors: Choi Kyu Sung , Kim Sunghwan , Kim Byung-Hoon , Jeon Hong Jin , Kim Jong-Hoon , Jang Joon Hwan , Jeong Bumseok
Published: August 2021

Precise remote evaluation of both suicide risk and psychiatric disorders is critical for suicide prevention as well as for psychiatric well-being. Using questionnaires is an alternative to labor-intensive diagnostic interviews in a large general population, but previous models for predicting suicide attempts suffered from low sensitivity. We developed and validated a deep graph neural network model that increased the prediction sensitivity of suicide risk in young adults (n = 17,482 for training; n = 14,238 for testing) using multi-dimensional questionnaires and suicidal ideation within 2 weeks as the prediction target. The best model achieved a sensitivity of 76.3%, specificity of 83.4%, and an area under curve of 0.878 (95% confidence interval, 0.855–0.899). We demonstrated that multi-dimensional deep features covering depression, anxiety, resilience, self-esteem, and clinico-demographic information contribute to the prediction of suicidal ideation. Our model might be useful for the remote evaluation of suicide risk in the general population of young adults for specific situations such as the COVID-19 pandemic.
A new argument against cooling by convective air eddies formed above sunlit zebra stripes
Authors: Pereszlényi Ádám , Száz Dénes , Jánosi Imre M. , Horváth Gábor
Published: August 2021

There is a long-lasting debate about the possible functions of zebra stripes. According to one hypothesis, periodical convective air eddies form over sunlit zebra stripes which cool the body. However, the formation of such eddies has not been experimentally studied. Using schlieren imaging in the laboratory, we found: downwelling air streams do not form above the white stripes of light-heated smooth or hairy striped surfaces. The influence of stripes on the air stream formation (facilitating upwelling streams and hindering horizontal stream drift) is negligible higher than 1–2 cm above the surface. In calm weather, upwelling air streams might form above sunlit zebra stripes, however they are blown off by the weakest wind, or even by the slowest movement of the zebra. These results forcefully contradict the thermoregulation hypothesis involving air eddies.
Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation
Authors: Edinger Fabian , Schmitt Christoph , Koch Christian , McIntosh J. Michael , Janciauskiene Sabina , Markmann Melanie , Sander Michael , Padberg Winfried , Grau Veronika
Published: August 2021

Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients suffering from respiratory or cardiac failure. The ECMO-associated morbidity and mortality depends to a large extent on the underlying disease and is often related to systemic inflammation, consecutive immune paralysis and sepsis. Here we tested the hypothesis that human α1-antitrypsin (SERPINA1) due to its anti-protease and anti-inflammatory functions may attenuate ECMO-induced inflammation. We specifically aimed to test whether intravenous treatment with α1-antitrypsin reduces the release of cytokines in response to 2 h of experimental ECMO. Adult rats were intravenously infused with α1-antitrypsin immediately before starting veno-arterial ECMO. We measured selected pro- and anti-inflammatory cytokines and found, that systemic levels of tumor necrosis factor-α, interleukin-6 and interleukin-10 increase during experimental ECMO. As tachycardia and hypertension developed in response to α1-antitrypsin, a single additional bolus of fentanyl and midazolam was given. Treatment with α1-antitrypsin and higher sedative doses reduced all cytokine levels investigated. We suggest that α1-antitrypsin might have the potential to protect against both ECMO-induced systemic inflammation and immune paralysis. More studies are needed to corroborate our findings, to clarify the mechanisms by which α1-antitrypsin inhibits cytokine release in vivo and to explore the potential application of α1-antitrypsin in clinical ECMO.
Effects of high-frequency nanosecond pulses on prostate cancer cells
Authors: Kiełbik Aleksander , Szlasa Wojciech , Novickij Vitalij , Szewczyk Anna , Maciejewska Magdalena , Saczko Jolanta , Kulbacka Julita
Published: August 2021

Electroporation with pulsed electric fields show a potential to be applied as an experimental focal therapy of tumors. Sub-microsecond regime of electric pulses displays unique electrophysical features operative in cells and membranes. Recently, MHz compression of nanosecond pulses electric fields (nsPEFs) bursts proved to enhance the effectiveness of the therapy. High morbidity of prostate cancer (PCa) and risk of overtreatment associated with this malignancy call for new minimal-invasive treatment alternative. Herein we present the in vitro study for developing applications based on this new technology. In this study, we used flow cytometric analysis, cell viability assay, caspase activity analysis, wound healing assay, confocal microscopy study, and immunofluorescence to investigate the biological effect of high-frequency nsPEFs on PCa cells. Our results show that high-frequency nsPEFs induces the permeabilization and cell death of PCa cells. The cytotoxicity is significantly enhanced in MHz compression of pulses and with the presence of extracellular Ca2+. High-frequency nsPEFs trigger changes in PCa cells’ cytoskeleton and their mobility. The presented data show a therapeutic potential of high-frequency nsPEFs in a PCa setting. The sub-microsecond regime of pulses can potentially be applied in nanosecond electroporation protocols for PCa treatment.
Transcriptomic profile of cationic channels in human pulmonary arterial hypertension
Authors: Perez-Vizcaino Francisco , Cogolludo Angel , Mondejar-Parreño Gema
Published: August 2021

The dysregulation of K+ channels is a hallmark of pulmonary arterial hypertension (PAH). Herein, the channelome was analyzed in lungs of patients with PAH in a public transcriptomic database. Sixty six (46%) mRNA encoding cationic channels were dysregulated in PAH with most of them downregulated (83%). The principal component analysis indicated that dysregulated cationic channel expression is a signature of the disease. Changes were very similar in idiopathic, connective tissue disease and congenital heart disease associated PAH. This analysis 1) is in agreement with the widely recognized pathophysiological role of TASK1 and KV1.5, 2) supports previous preliminary reports pointing to the dysregulation of several K+ channels including the downregulation of KV1.1, KV1.4, KV1.6, KV7.1, KV7.4, KV9.3 and TWIK2 and the upregulation of KCa1.1 and 3) points to other cationic channels dysregulated such as Kv7.3, TALK2, CaV1 and TRPV4 which might play a pathophysiological role in PAH. The significance of other changes found in Na+ and TRP channels remains to be investigated.