bluuebunny/crossref_metadata_2025 huggingface dataset:
Hidden Upwelling Systems Associated With Major Western Boundary Currents
Authors: Liao Fanglou , Liang Xinfeng , Li Yun , Spall Michael
Published: March 2022

Western boundary currents (WBCs) play an essential role in regulating global climate. In contrast to their widely examined horizontal motions, less attention has been paid to vertical motions associated with WBCs. Here, we examine vertical motions associated with the major WBCs by analyzing vertical velocity from five ocean synthesis products and one eddy‐resolving ocean simulation. These data reveal robust and intense subsurface upwelling systems, which are primarily along isopycnal surfaces, in five major subtropical WBC systems. These upwelling systems are part of basin‐scale overturning circulations and are likely driven by meridional pressure gradients along the western boundary. Globally, the WBC upwelling contributes significantly to the vertical transport of water mass and ocean properties and is an essential yet overlooked branch of the global ocean circulation. In addition, the WBC upwelling intersects the oceanic euphotic and mixed layers, and thus likely plays an important role in ocean biological and chemical processes by transporting nutrients, carbon and other tracers vertically inside the ocean. This study calls for more research into the dynamics of the WBC upwelling and their role in the ocean and climate systems.
Secular Variability of the Upwelling at the Canaries Latitude: An Instrumental Approach
Authors: Gallego D. , García‐Herrera R. , Mohino E. , Losada T. , Rodríguez‐Fonseca B.
Published: March 2022

In this research we make use of historical wind direction observations to assemble an instrumental upwelling intensity index (the so‐called Directional Upwelling Index [DUI]) for the coast of Northwest Africa between 26° and 33°N and from 1825 to 2014. The DUI is defined as the persistence of the alongshore winds at the coast and unlike other upwelling indices, it relies on observed wind direction solely, avoiding the suspected bias toward increasing wind speed of historical wind observations documented in previous research. We have found that between June and October, when the upwelling intensity in the area is at its seasonal maximum, the persistence of the north‐easterlies measured by the DUI is significantly related to the alongshore wind stress and subsequently with Sea Surface Temperature anomalies at the coast of NW Africa. The analysis of the DUI record does not display a consistent long‐term trend but an oscillatory behavior. At interannual time scales this variability can be linked to the changes in the strength and location of the subtropical north Atlantic high‐pressure center and at multidecadal scales, the upwelling seems mainly driven by the Atlantic Multidecadal Variability through the modulation exerted by this climatic pattern on the intensity of the Saharan low.
High‐Resolution Large Eddy Simulations of Vortex Dynamics Over Ripple Defects Under Oscillatory Flow
Authors: Jin C. , Coco G. , Tinoco R. O. , Ranjan P. , Gong Z. , Dutta S. , San Juan J. E. , Friedrich H.
Published: March 2022

We carried out high‐resolution Large Eddy Simulations to study the three‐dimensional hydrodynamic characteristics over regular and irregular wave‐generated ripples. Two types of irregularities in ripple crestlines are considered, namely ripples with a termination defect and with a bifurcation defect. Over regular ripples, the flow and vortex structures vary in the spanwise direction, displaying evident three‐dimensional vortex structures. Compared to regular ripples, the presence of a bifurcation or a termination defect implies local variations in ripple height and spacing. As a result, the maximum velocity, vortex strength and the position of the vortex center over ripples neighboring a defect are all affected by the presence of the defect. The maximum velocity at the ripple crest neighboring a defect is linearly related to the position of the vortex center. The presence of defects induces an asymmetric distribution of shear stress and sediment flux that will ultimately affect bedform evolution.
Challenges and Capabilities in Estimating Snow Mass Intercepted in Conifer Canopies With Tree Sway Monitoring
Authors: Raleigh Mark S. , Gutmann Ethan D. , Van Stan John T. , Burns Sean P. , Blanken Peter D. , Small Eric E.
Published: March 2022

Snowpack accumulation in forested watersheds depends on the amount of snow intercepted in the canopy and its partitioning into sublimation, unloading, and melt. A lack of canopy snow measurements limits our ability to evaluate models that simulate canopy processes and predict snowpack. We tested whether monitoring changes in wind‐induced tree sway is a viable technique for detecting snow interception and quantifying canopy snow water equivalent (SWE). Over a 6 year period in Colorado, we monitored hourly sway of two conifers, each instrumented with an accelerometer sampling at 12 Hz. We developed an approach to distinguish changes in sway frequency due to thermal effects on tree rigidity versus intercepted snow mass. Over 60% of days with canopy snow had a sway signal that could not be distinguished from thermal effects. However, larger changes in tree sway could not generally be attributed to thermal effects, and canopy snow was present 93%–95% of the time, as confirmed with classified PhenoCam imagery. Using sway tests, we converted changes in sway to canopy SWE, which were correlated with total snowstorm amounts from a nearby SNOTEL site (Spearman r = 0.72 to 0.80, p < 0.001). Greater canopy SWE was associated with storm temperatures between −7°C and 0°C and wind speeds less than 4 m s−1. Lower canopy SWE prevailed in storms with lower temperatures and higher wind speeds. Monitoring tree sway is a viable approach for quantifying canopy SWE, but challenges remain in converting changes in sway to mass and distinguishing thermal and snow mass effects on tree sway.
Concerted BAG3 and SIRPα blockade impairs pancreatic tumor growth
Authors: De Marco Margot , Gauttier Vanessa , Pengam Sabrina , Mary Caroline , Ranieri Bianca , Basile Anna , Festa Michela , Falco Antonia , Reppucci Francesca , Cammarota Anna Lisa , Acernese Fausto , De Laurenzi Vincenzo , Sala Gianluca , Brongo Sergio , Miyasaka Masayuki , Shalapour Shabnam , Vanhove Bernard , Poirier Nicolas , Iaccarino Roberta , Karin Michael , Turco Maria Caterina , Rosati Alessandra , Marzullo Liberato
Published: March 2022

The BAG3- and SIRPα- mediated pathways trigger distinct cellular targets and signaling mechanisms in pancreatic cancer microenvironment. To explore their functional connection, we investigated the effects of their combined blockade on cancer growth in orthotopic allografts of pancreatic cancer mt4–2D cells in immunocompetent mice. The anti-BAG3 + anti-SIRPα mAbs treatment inhibited (p = 0.007) tumor growth by about the 70%; also the number of metastatic lesions was decreased, mostly by the effect of the anti-BAG3 mAb. Fibrosis and the expression of the CAF activation marker α-SMA were reduced by about the 30% in animals treated with anti-BAG3 mAb compared to untreated animals, and appeared unaffected by treatment with the anti-SIRPα mAb alone; however, the addition of anti-SIRPα to anti-BAG3 mAb in the combined treatment resulted in a > 60% (p < 0.0001) reduction of the fibrotic area and a 70% (p < 0.0001) inhibition of CAF α-SMA positivity. Dendritic cells (DCs) and CD8+ lymphocytes, hardly detectable in the tumors of untreated animals, were modestly increased by single treatments, while were much more clearly observable (p < 0.0001) in the tumors of the animals subjected to the combined treatment. The effects of BAG3 and SIRPα blockade do not simply reflect the sum of the effects of the single blockades, indicating that the two pathways are connected by regulatory interactions and suggesting, as a proof of principle, the potential therapeutic efficacy of a combined BAG3 and SIRPα blockade in pancreatic cancer.
The use of the paramedian forehead flap alone or in combination with other techniques in the reconstruction of periocular defects and orbital exenterations
Authors: Ang Terence W. , Juniat Valerie , O’Rourke Micheal , Slattery James , O’Donnell Brett , McNab Alan A. , Hardy Thomas G. , Caplash Yugesh , Selva Dinesh
Published: March 2022

Purpose

The paramedian forehead flap (PMFF) is a reconstructive option for large eyelid defects and orbital exenterations. We report a series of cases where PMFF reconstruction was carried out at various institutions in Australia.

Methods

This study was a multi-centre, retrospective, non-comparative case series investigating the clinical outcomes of the PMFF for reconstructing periocular defects and orbital exenterations.

Results

This case series describes twenty-seven patients (Female = 15, Male = 12), operated between 1991 to 2019, with a median age of 81 years (range: 45–93 years). Defect locations involved combinations of the medial canthus (16/27, 59.3%), upper eyelids (7/27, 25.9%), lower eyelid (4/27, 14.8%), both upper and lower eyelids (5/27, 18.5%), and orbital (7/27, 25.9%). There were no cases of flap necrosis. Minor post-operative complications were observed in ten patients with the most common being lagophthalmos. Median duration of follow-up was 17months (Range: 2months- 23years).

Conclusions

The PMFF is a versatile reconstructive tool for a range of periocular defects and orbital exenterations with minor post-operative complications.
Intestinal AMPK modulation of microbiota mediates crosstalk with brown fat to control thermogenesis
Authors: Zhang Eryun , Jin Lihua , Wang Yangmeng , Tu Jui , Zheng Ruirong , Ding Lili , Fang Zhipeng , Fan Mingjie , Al-Abdullah Ismail , Natarajan Rama , Ma Ke , Wang Zhengtao , Riggs Arthur D. , Shuck Sarah C. , Yang Li , Huang Wendong
Published: March 2022

The energy-dissipating capacity of brown adipose tissue through thermogenesis can be targeted to improve energy balance. Mammalian 5′-AMP-activated protein kinase, a key nutrient sensor for maintaining cellular energy status, is a known therapeutic target in Type II diabetes. Despite its well-established roles in regulating glucose metabolism in various tissues, the functions of AMPK in the intestine remain largely unexplored. Here we show that AMPKα1 deficiency in the intestine results in weight gain and impaired glucose tolerance under high fat diet feeding, while metformin administration fails to ameliorate these metabolic disorders in intestinal AMPKα1 knockout mice. Further, AMPKα1 in the intestine communicates with brown adipose tissue to promote thermogenesis. Mechanistically, we uncover a link between intestinal AMPKα1 activation and BAT thermogenic regulation through modulating anti-microbial peptide-controlled gut microbiota and the metabolites. Our findings identify AMPKα1-mediated mechanisms of intestine-BAT communication that may partially underlie the therapeutic effects of metformin.
Antibody escape and global spread of SARS-CoV-2 lineage A.27
Authors: Kaleta Tamara , Kern Lisa , Hong Samuel Leandro , Hölzer Martin , Kochs Georg , Beer Julius , Schnepf Daniel , Schwemmle Martin , Bollen Nena , Kolb Philipp , Huber Magdalena , Ulferts Svenja , Weigang Sebastian , Dudas Gytis , Wittig Alice , Jaki Lena , Padane Abdou , Lagare Adamou , Salou Mounerou , Ozer Egon Anderson , Nnaemeka Ndodo , Odoom John Kofi , Rutayisire Robert , Benkahla Alia , Akoua-Koffi Chantal , Ouedraogo Abdoul-Salam , Simon-Lorière Etienne , Enouf Vincent , Kröger Stefan , Calvignac-Spencer Sébastien , Baele Guy , Panning Marcus , Fuchs Jonas
Published: March 2022

In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected in 31 countries. Phylogeographic analyses of A.27 sequences obtained from national and international databases reveal a global spread of this lineage through multiple introductions from its inferred origin in Western Africa. Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G. Neutralization assays demonstrate an escape of A.27 from convalescent and vaccine-elicited antibody-mediated immunity. Moreover, the therapeutic monoclonal antibody Bamlanivimab and partially the REGN-COV2 cocktail fail to block infection by A.27. Our data emphasize the need for continued global monitoring of novel lineages because of the independent evolution of new escape mutations.
Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia
Authors: Lee Miyoung , Hamilton Jamie A. G. , Talekar Ganesh R. , Ross Anthony J. , Michael Langston , Rupji Manali , Dwivedi Bhakti , Raikar Sunil S. , Boss Jeremy , Scharer Christopher D. , Graham Douglas K. , DeRyckere Deborah , Porter Christopher C. , Henry Curtis J.
Published: March 2022

The incidence of obesity is rising with greater than 40% of the world’s population expected to be overweight or suffering from obesity by 2030. This is alarming because obesity increases mortality rates in patients with various cancer subtypes including leukemia. The survival differences between lean patients and patients with obesity are largely attributed to altered drug pharmacokinetics in patients receiving chemotherapy; whereas, the direct impact of an adipocyte-enriched microenvironment on cancer cells is rarely considered. Here we show that the adipocyte secretome upregulates the surface expression of Galectin-9 (GAL-9) on human B-acute lymphoblastic leukemia cells (B-ALL) which promotes chemoresistance. Antibody-mediated targeting of GAL-9 on B-ALL cells induces DNA damage, alters cell cycle progression, and promotes apoptosis in vitro and significantly extends the survival of obese but not lean mice with aggressive B-ALL. Our studies reveal that adipocyte-mediated upregulation of GAL-9 on B-ALL cells can be targeted with antibody-based therapies to overcome obesity-induced chemoresistance.
Distribution and quantification of remotely generated Wigner negativity
Authors: Xiang Yu , Liu Shuheng , Guo Jiajie , Gong Qihuang , Treps Nicolas , He Qiongyi , Walschaers Mattia
Published: March 2022

Wigner negativity, as a well-known indicator of nonclassicality, plays an essential role in quantum computing and simulation using continuous-variable systems. The conditional preparation of Wigner-negative states through appropriate non-Gaussian operations on an auxiliary mode is common procedure in quantum optics experiments. Motivated by the demand of real-world quantum network, here we investigate the remote creation and distribution of Wigner negativity in the multipartite scenario from a quantitative perspective. By establishing a monogamy relation akin to the generalized Coffman-Kundu-Wootters inequality, we show that the amount of Wigner negativity cannot be freely distributed among different modes. Moreover, for photon subtraction—one of the main experimentally realized non-Gaussian operations—we provide an intuitive method to quantify remotely generated Wigner negativity. Our results pave the way for exploiting Wigner negativity as a valuable resource for numerous quantum information protocols based on non-Gaussian scenario.
Inverted fine structure of a 6H-SiC qubit enabling robust spin-photon interface
Authors: Breev I. D. , Shang Z. , Poshakinskiy A. V. , Singh H. , Berencén Y. , Hollenbach M. , Nagalyuk S. S. , Mokhov E. N. , Babunts R. A. , Baranov P. G. , Suter D. , Tarasenko S. A. , Astakhov G. V. , Anisimov A. N.
Published: March 2022

Controllable solid-state spin qubits are currently becoming useful building blocks for applied quantum technologies. Here, we demonstrate that in a specific type of silicon-vacancy in the 6H-SiC polytype the excited-state fine structure is inverted, compared to 4H-SiC. From the angular polarization dependencies of the emission, we reconstruct the spatial symmetry and determine the optical selection rules depending on the local deformation and spin–orbit interaction. We show that this system is well suited for the implementation of robust spin–photon entanglement schemes. Furthermore, the inverted fine structure leads to unexpected behavior of the spin readout contrast. It vanishes and recovers with lattice cooling due to two competing optical spin pumping mechanisms. Our experimental and theoretical approaches provide a deep insight into the optical and spin properties of atomic-scale qubits in SiC required for quantum communication and distributed quantum information processing.
Association between long-term usage of acetylcholinesterase inhibitors and lung cancer in the elderly: a nationwide cohort study
Authors: Liu Chien-Ting , Yang Chuan-Chi , Chien Wu-Chien , Chung Chi-Hsiang , Tsai Chien-Sung , Tsai Yi-Ting , Lin Chih-Yuan , Lin Yi-Chang , Chen Yi-Shi , Tzeng Nian-Sheng
Published: March 2022

This retrospective cohort study aimed to evaluate the association between acetylcholinesterase inhibitors (AChEI) usage and the risk of lung cancer. Data from 116,106 new users of AChEI and 348,318, at a ratio of 1:3, matched by age, sex, and index-year, between 2000 and 2015 controls were obtained from the Taiwan Longitudinal Health Insurance Database in this cohort study. The Cox regression model was used to compare the risk of lung cancer. The adjusted hazard ratio (aHR) of lung cancer for AChEI users was 1.198 (95% confidence interval [CI] = 0.765–1.774, p = 0.167). However, the adjusted HR for patients aged ≥ 65 was adjusted to HR: 1.498 (95% CI = 1.124–1.798, p < 0.001), in contrast to the comparison groups. In addition, patients with comorbidities such as pneumonia, bronchiectasis, pneumoconiosis, pulmonary alveolar pneumonopathy, hypertension, stroke, coronary artery disease, diabetes mellitus, chronic kidney disease, depression, anxiety, smoking-related diseases, dementia, and seeking medical help from medical centers and regional hospitals, were associated with a higher risk in lung cancer. Furthermore, longer-term usage of rivastigmine (366–730 days, ≥ 731 days) and galantamine (≥ 731 days) was associated with the risk of lung cancer. AChEI increased the risk of lung cancer in the older aged patients, several comorbidities, and a longer-term usage of rivastigmine and galantamine. Therefore, physicians should estimate the risks and benefits of AChEI usage and avoid prescribing antidepressants concurrently.
Analysis of a silicon comb structure using an inverse Talbot–Lau neutron grating interferometer
Authors: Kim Youngju , Kim Daeseung , Hussey Daniel S. , Kim Jongyul , Mirzaei Mona , Pushin Dmitry A. , Clark Charles W. , Lee Seung Wook
Published: March 2022

We describe an inverse Talbot–Lau neutron grating interferometer that provides an extended autocorrelation length range for quantitative dark-field imaging. To our knowledge, this is the first report of a Talbot–Lau neutron grating interferometer (nTLI) with inverse geometry. We demonstrate a range of autocorrelation lengths (ACL) starting at low tens of nanometers, which is significantly extended compared to the ranges of conventional and symmetric setups. ACLs from a minimum of 44 nm to the maximum of 3.5 μm were presented for the designed wavelength of 4.4 Å in experiments. Additionally, the inverse nTLI has neutron-absorbing gratings with an optically thick gadolinium oxysulfide (Gadox) structure, allowing it to provide a visibility of up to 52% while maintaining a large field of view of approximately 100 mm × 100 mm. We demonstrate the application of our interferometer to quantitative dark-field imaging by using diluted polystyrene particles in an aqueous solution and silicon comb structures. We obtain quantitative structural information of the sphere size and concentration of diluted polystyrene particles and the period, height, and duty cycle of the silicon comb structures. The optically thick Gadox structure of the analyzer grating also provides improved characteristics for the correction of incoherent neutron scattering in an aqueous solution compared to the symmetric nTLI.
Diffusive model to assess the release of chemicals from a material under intermittent release conditions
Authors: Frezzato Diego , Stocco Gianluca , Boscaro Enrico , Ferraro Marco , Tapparo Andrea
Published: March 2022

We consider the archetype situation of a chemical species that diffuses in a material and irreversibly escapes through the interface. In our setup, the interface switches between two states corresponding to ‘release phase’ (absorbing boundary) during which the species is released to the exterior, and ‘pause phase’ (reflecting boundary) during which the species is not released and its concentration profile inside the material partially relaxes back to uniformity. By combining numerical solution of the diffusion equation and statistical analysis of the outcomes, we derive upper and lower bounds and an empirical approximation for the amount of species released up to a certain time, in which the only information about the release-pause alternation schedule is the number of release phases and the average duration of a release phase. The methodology is developed thinking especially to dermal exposure assessment in the case of a slab-like homogeneous material irreversibly releasing chemicals during a number of contacts. However, upon proper extensions, this approach might be useful for inspecting other situations that are encountered, for instance, when dealing with leakage of chemicals in environmental contexts and regulatory toxicology.
Anti-inflammatory effects of an autologous gold-based serum therapy in osteoarthritis patients
Authors: Feldt Jessica , Donaubauer Anna-Jasmina , Welss Jessica , Schneider Ulrich , Gaipl Udo S. , Paulsen Friedrich
Published: March 2022

Osteoarthritis (OA) involves activation and recruitment of immune cells to affected joints, including the production of pro-inflammatory cytokines. Here, a gold-based autologous serum therapy is investigated for its effect on peripheral blood cell composition and cytokine levels in OA patients. From six OA patients serum and blood samples were collected before and after second therapy treatment for analysis of peripheral blood cell composition as well as cytokine levels compared to control samples. This therapy significantly downregulates CD4+ T cells and B cells in OA patients after second treatment compared to healthy controls. Monocytes are significantly upregulated in patients after second treatment Serum IL-9 and TNF-α levels are downregulated in patients after second treatment compared to healthy control serum. The activation status of immune cells was modulated after therapy in patients. Anti-inflammatory effects of the peripheral blood cell composition in OA patients can be seen after therapy treatment. After two treatments IL-9 and TNF-α are significantly downregulated in patient serum. Here, primary data of a new autologous therapy for OA treatment and its modulatory effects on cytokines are presented.
Intracranial recordings in humans reveal specific hippocampal spectral and dorsal vs. ventral connectivity signatures during visual, attention and memory tasks
Authors: Castelhano João , Duarte Isabel , Bernardino Inês , Pelle Federica , Francione Stefano , Sales Francisco , Castelo-Branco Miguel
Published: March 2022

Invasive brain recordings using many electrodes across a wide range of tasks provide a unique opportunity to study the role of oscillatory patterning and functional connectivity. We used large-scale recordings (stereo EEG) within and beyond the human hippocampus to investigate the role of distinct frequency oscillations during real-time execution of visual, attention and memory tasks in eight epileptic patients. We found that activity patterns in the hippocampus showed task and frequency dependent properties. Importantly, we found distinct connectivity signatures, in particular concerning parietal-hippocampal connectivity, thus revealing large scale synchronization of networks involved in memory tasks. Comparing the power per frequency band, across tasks and hippocampal regions (anterior/posterior) we confirmed a main effect of frequency band (p = 0.002). Gamma band activity was higher for visuo-spatial memory tasks in the anterior hippocampus. Further, we found that alpha and beta band activity in posterior hippocampus had larger modulation for high memory load visual tasks (p = 0.004). Three functional connectivity task related networks were identified: (dorsal) parietal-hippocampus (visual attention and memory), ventral stream- hippocampus and hippocampal-frontal connections (mainly tasks involving face recognition or object based search). These findings support the critical role of oscillatory patterning in the hippocampus during visual and memory tasks and suggests the presence of task related spectral and functional connectivity signatures. These results show that the use of large scale human intracranial recordings can validate the role of oscillatory and functional connectivity patterns across a broad range of cognitive domains.
Optimizing surgical outcome of auricular keloid with a novel multimodal approach
Authors: Hung Yi-Teng , Lin Shih-Min , Tzeng I-Shiang , Ng Chau Yee
Published: March 2022

Various treatments are available for auricular keloids, but none has an absolute advantage. A practical and safe therapy to optimize the surgical outcome for auricular keloids is needed. We adopted a multimodal treatment of surgical enucleation, core fillet flap reconstruction, intraoperative corticosteroid injection, and immediate postoperative radiotherapy. There were no routine intralesional corticosteroid injections during follow-up. Keloid recurrences, complications, and risk factors for recurrences were analyzed. The outcome was compared with other published literatures. 45 auricular keloids were included in this study. 85.7% were female with an average age of 27.1 ± 7.5 years, and averaged size was 1.8 × 1.2 ± 0.9 × 0.6 cm. 71.1% were located at ear helix with 28.9% at the ear lobe. Nine keloids were classified as Chang-Park classification type I, 30 for type II, two for type III, and four for IV. The average radiation dosage was 1578.6 cGy. The recurrence rate was 6.7% at an average 24.1-month follow-up. There were no complications of surgery, radiotherapy, and intralesional corticosteroid injection. Our recurrence rate was lower than those in mono-adjuvant therapies of intraoperative corticosteroid injection or radiotherapy. This one-session multimodal approach optimizes treating auricular keloids with a low recurrence rate and minimal post-radiation and long-term corticosteroid injection-related complications.
High-content analysis of microRNAs involved in the phenotype regulation of vascular smooth muscle cells
Authors: Zhang Jian , Starkuviene Vytaute , Erfle Holger , Wang Zhaohui , Gunkel Manuel , Zeng Ziwei , Sticht Carsten , Kan Kejia , Rahbari Nuh , Keese Michael
Published: March 2022

In response to vascular injury vascular smooth muscle cells (VSMCs) alternate between a differentiated (contractile) and a dedifferentiated (synthetic) state or phenotype. Although parts of the signaling cascade regulating the phenotypic switch have been described, the role of miRNAs is still incompletely understood. To systematically address this issue, we have established a microscopy-based quantitative assay and identified 23 miRNAs that induced contractile phenotypes when over-expressed. These were then correlated to miRNAs identified from RNA-sequencing when comparing cells in the contractile and synthetic states. Using both approaches, six miRNAs (miR-132-3p, miR-138-5p, miR-141-3p, miR-145-5p, miR-150-5p, and miR-22-3p) were filtered as candidates that induce the phenotypic switch from synthetic to contractile. To identify potentially common regulatory mechanisms of these six miRNAs, their predicted targets were compared with five miRNAs sharing ZBTB20, ZNF704, and EIF4EBP2 as common potential targets and four miRNAs sharing 16 common potential targets. The interaction network consisting of these 19 targets and additional 18 hub targets were created to facilitate validation of miRNA-mRNA interactions by suggesting the most plausible pairs. Furthermore, the information on drug candidates was integrated into the network to predict novel combinatorial therapies that encompass the complexity of miRNAs-mediated regulation. This is the first study that combines a phenotypic screening approach with RNA sequencing and bioinformatics to systematically identify miRNA-mediated pathways and to detect potential drug candidates to positively influence the phenotypic switch of VSMCs.
Viral load of SARS-CoV-2 in droplets and bioaerosols directly captured during breathing, speaking and coughing
Authors: Johnson Tyler J. , Nishida Robert T. , Sonpar Ashlesha P. , Lin Yi-Chan James , Watson Kimberley A. , Smith Stephanie W. , Conly John M. , Evans David H. , Olfert Jason S.
Published: March 2022

Determining the viral load and infectivity of SARS-CoV-2 in macroscopic respiratory droplets, bioaerosols, and other bodily fluids and secretions is important for identifying transmission modes, assessing risks and informing public health guidelines. Here we show that viral load of SARS-CoV-2 Ribonucleic Acid (RNA) in participants’ naso-pharyngeal (NP) swabs positively correlated with RNA viral load they emitted in both droplets >10 $$\upmu \hbox {m}$$

μ
m

and bioaerosols <10 $$\upmu \hbox {m}$$

μ
m

directly captured during the combined expiratory activities of breathing, speaking and coughing using a standardized protocol, although the NP swabs had $$\approx$$
≈
10$$^3\times$$

3

×

more RNA on average. By identifying highly-infectious individuals (maximum of 18,000 PFU/mL in NP), we retrieved higher numbers of SARS-CoV-2 RNA gene copies in bioaerosol samples (maximum of 4.8$${\times }10^{5}$$

×

10
5

gene copies/mL and minimum cycle threshold of 26.2) relative to other studies. However, all attempts to identify infectious virus in size-segregated droplets and bioaerosols were negative by plaque assay (0 of 58). This outcome is partly attributed to the insufficient amount of viral material in each sample (as indicated by SARS-CoV-2 gene copies) or may indicate no infectious virus was present in such samples, although other possible factors are identified.
A Lab-in-a-Fiber optofluidic device using droplet microfluidics and laser-induced fluorescence for virus detection
Authors: Parker Helen E. , Sengupta Sanghamitra , Harish Achar V. , Soares Ruben R. G. , Joensson Haakan N. , Margulis Walter , Russom Aman , Laurell Fredrik
Published: March 2022

Microfluidics has emerged rapidly over the past 20 years and has been investigated for a variety of applications from life sciences to environmental monitoring. Although continuous-flow microfluidics is ubiquitous, segmented-flow or droplet microfluidics offers several attractive features. Droplets can be independently manipulated and analyzed with very high throughput. Typically, microfluidics is carried out within planar networks of microchannels, namely, microfluidic chips. We propose that fibers offer an interesting alternative format with key advantages for enhanced optical coupling. Herein, we demonstrate the generation of monodisperse droplets within a uniaxial optofluidic Lab-in-a-Fiber scheme. We combine droplet microfluidics with laser-induced fluorescence (LIF) detection achieved through the development of an optical side-coupling fiber, which we term a periscope fiber. This arrangement provides stable and compact alignment. Laser-induced fluorescence offers high sensitivity and low detection limits with a rapid response time making it an attractive detection method for in situ real-time measurements. We use the well-established fluorophore, fluorescein, to characterize the Lab-in-a-Fiber device and determine the generation of $$\sim$$
∼
 0.9 nL droplets. We present characterization data of a range of fluorescein concentrations, establishing a limit of detection (LOD) of 10 nM fluorescein. Finally, we show that the device operates within a realistic and relevant fluorescence regime by detecting reverse-transcription loop-mediated isothermal amplification (RT-LAMP) products in the context of COVID-19 diagnostics. The device represents a step towards the development of a point-of-care droplet digital RT-LAMP platform.
Maturation of the internal auditory canal and posterior petrous bone with relevance to lateral and posterolateral skull base approaches
Authors: Rennert Robert C. , Brandel Michael G. , Steinberg Jeffrey A. , Friedman Rick A. , Couldwell William T. , Fukushima Takanori , Day John D. , Khalessi Alexander A. , Levy Michael L.
Published: March 2022

Anatomic knowledge of the internal auditory canal (IAC) and surrounding structures is a prerequisite for performing skull base approaches to the IAC. We herein perform a morphometric analysis of the IAC and surgically relevant aspects of the posterior petrous bone during pediatric maturation, a region well-studied in adults but not children. Measurements of IAC length (IAC-L), porus (IAC-D) and midpoint (IAC-DM) diameter, and distance from the porus to the common crus (CC; P-CC) and posterior petrosal surface (PPS) to the posterior semicircular canal (PSC; PPS-PSC) were made on thin-cut axial CT scans from 60 patients (grouped by ages 0–3, 4–7, 8–11 12–15, 16–18, and > 18 years). IAC-L increased 27.5% from 8.7 ± 1.1 at age 0–3 to 11.1 ± 1.1 mm at adulthood (p = 0.001), with the majority of growth occurring by ages 8–11. IAC-D (p = 0.52) and IAC-DM (p = 0.167) did not significantly change from ages 0–3 to adult. P-CC increased 31.1% from 7.7 ± 1.5 at age 0–3 to 10.1 ± 1.5 mm at adulthood (p = 0.019). PPS-PSC increased 160% from 1.5 ± 0.7 at age 0–3 to 3.9 ± 1.2 mm at adulthood (p < 0.001). The majority of growth in P-CC and PPS-PSC occurred by ages 12–15. Knowledge of these patterns may facilitate safe exposure of the IAC in children.
Negativity in delayed affective recall is related to the borderline personality trait
Authors: Maraz Aniko , Nagy Tamás , Ziegler Matthias
Published: March 2022

The present study assessed selected factors that contribute to the recollection of emotional memories over time. Participants with high-trait borderline personality disorder (BPD) watched a randomly selected positive, negative, or neutral character in a video clip (stimulus) and were asked to recall the content immediately, then 2, 4, and 6 days later. In the final sample (N = 558, average age: 33 years, 65% female), general impression had the strongest effect on recall after accounting for the effect of current mood, extremity of the responses, and level of BPD, regardless of stimulus valence. The level of BPD had an effect only when negative evaluative wording (e.g., “guilty”) was used. In conclusion, people with high-trait BPD tend to remember negative stimuli more negatively over time (unlike neutral or positive stimuli), and this effect is mostly related to general impression.
Radiotherapy alters expression of molecular targets in prostate cancer in a fractionation- and time-dependent manner
Authors: Eke Iris , Aryankalayil Molykutty J. , Bylicky Michelle A. , Makinde Adeola Y. , Liotta Lance , Calvert Valerie , Petricoin Emanuel F. , Graves Edward E. , Coleman C. Norman
Published: March 2022

The efficacy of molecular targeted therapy depends on expression and enzymatic activity of the target molecules. As radiotherapy modulates gene expression and protein phosphorylation dependent on dose and fractionation, we analyzed the long-term effects of irradiation on the post-radiation efficacy of molecular targeted drugs. We irradiated prostate cancer cells either with a single dose (SD) of 10 Gy x-ray or a multifractionated (MF) regimen with 10 fractions of 1 Gy. Whole genome arrays and reverse phase protein microarrays were used to determine gene expression and protein phosphorylation. Additionally, we evaluated radiation-induced pathway activation with the Ingenuity Pathway Analysis software. To measure cell survival and sensitivity to clinically used molecular targeted drugs, we performed colony formation assays. We found increased activation of several pathways regulating important cell functions such as cell migration and cell survival at 24 h after MF irradiation or at 2 months after SD irradiation. Further, cells which survived a SD of 10 Gy showed a long-term upregulation and increased activity of multiple molecular targets including AKT, IGF-1R, VEGFR2, or MET, while HDAC expression was decreased. In line with this, 10 Gy SD cells were more sensitive to target inhibition with Capivasertib or Ipatasertib (AKTi), BMS-754807 (IGF-1Ri), or Foretinib (VEGFR2/METi), but less sensitive to Panobinostat or Vorinostat (HDACi). In summary, understanding the molecular short- and long-term changes after irradiation can aid in optimizing the efficacy of multimodal radiation oncology in combination with post-irradiation molecularly-targeted drug treatment and improving the outcome of prostate cancer patients.
Effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and its possible mechanisms
Authors: Cheng Lan , Fu Qianyu , Zhou Longhua , Fan Yuqin , Liu Fenfen , Fan Yuanyuan , Zhang Xin , Lin Weiqing , Wu Xiaohe
Published: March 2022

The current study evaluated the effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and investigated its possible mechanisms. 124 patients were randomized to receive 25 mg empagliflozin QD, or placebo double blind for 12 weeks. Patients underwent 24-h ABPM. Endothelial function and arterial stiffness were also measured prior to randomization and at week 12. At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h SBP was − 8.14 mmHg (95% CI − 10.32, − 3.96,P = 0.005). At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h DBP was − 5.27 mmHg (95% CI − 8.19, − 1.35,P < 0.001). Changes in office BP were consistent with ABPM. Empagliflozin was well tolerated. Empagliflozin was associated with significant and clinically meaningful reductions in BP versus placebo in Chinese elderly patients with type 2 diabetes and hypertension. The underlying mechanisms possiblely at least in part were the improvements of endothelial function and arterial stiffness associated with empagliflozin.

Registration number: ChiCTR2100054678, Registration date: December 23, 2021.
Writing and reading with the longitudinal component of light using carbazole-containing azopolymer thin films
Authors: Porfirev Alexey , Khonina Svetlana , Ivliev Nikolay , Meshalkin Alexei , Achimova Elena , Forbes Andrew
Published: March 2022

It is well known that azobenzene-containing polymers (azopolymers) are sensitive to the polarization orientation of the illuminating radiation, with the resulting photoisomerization inducing material transfer at both the meso- and macroscale. As a result, azopolymers are efficient and versatile photonic materials, for example, they are used for the fabrication of linear diffraction gratings, including subwavelength gratings, microlens arrays, and spectral filters. Here we propose to use carbazole-containing azopolymer thin films to directly visualize the longitudinal component of the incident laser beam, a crucial task for the realization of 3D structured light yet remaining experimentally challenging. We demonstrate the approach on both scalar and vectorial states of structured light, including higher-order and hybrid cylindrical vector beams. In addition to detection, our results confirm that carbazole-containing azopolymers are a powerful tool material engineering with the longitudinal component of the electric field, particularly to fabricate microstructures with unusual morphologies that differentiate from the total intensity distribution of the writing laser beam.
Waste tea residue adsorption coupled with electrocoagulation for improvement of copper and nickel ions removal from simulated wastewater
Authors: Jean Claude Nizeyimana , Shanshan Lin , Khan Junaid , Yifeng Wu , dongxu Han , Xiangru Liu
Published: March 2022

The present research involves removing copper and nickel ions from synthesized wastewater by using a simple, cheap, cost-effective, and sustainable activated green waste tea residue (AGWTR) adsorption coupled with electrocoagulation (ADS/EC) process in the presence of iron electrodes. By considering previous studies, their adsorbents used for treating their wastewaters firstly activate them by applying either chemicals or activating agents. However, our adsorbent was prepared without applying neither chemicals nor any activating agents. The operating parameters such as pH, hydraulic retention time, adsorbent dose, initial concentration, current density, and operating cost for both metals were optimized. In ADS/EC, the removal efficiency was obtained as 100% for copper and 99.99% for nickel ions. After the ADS/EC process, Fourier transform infrared (FT-IR) spectroscopy, Scanning Electron Microscopy (SEM) and Energy-dispersive X-ray spectroscopy (EDS) analysis were used to characterize the adsorbent green waste tea residue. The adsorption isotherm and kinetic model results showed that the Langmuir and the pseudo-second-order were well-fitted to the experimental adsorption data better than the Freundlich and pseudo-first-order models for both Cu2+ and Ni2+ with their maximum adsorption capacity of 15.6 and 15.9 mg g−1, respectively. The above results give an option to recycle the metal-based industrial effluents, tea industry-based wastes, enabling a waste-to-green technique for adsorbing and removing the heavy metals and other pollutants in water.
Scaling SARS-CoV-2 wastewater concentrations to population estimates of infection
Authors: Kaplan Edward H. , Zulli Alessandro , Sanchez Marcela , Peccia Jordan
Published: March 2022

Monitoring the progression of SARS-CoV-2 outbreaks requires accurate estimation of the unobservable fraction of the population infected over time in addition to the observed numbers of COVID-19 cases, as the latter present a distorted view of the pandemic due to changes in test frequency and coverage over time. The objective of this report is to describe and illustrate an approach that produces representative estimates of the unobservable cumulative incidence of infection by scaling the daily concentrations of SARS-CoV-2 RNA in wastewater from the consistent population contribution of fecal material to the sewage collection system.
Three cases of discontinuous refractive index in metamaterial study
Authors: Wegrowski Antoine , Wang Wei-Chih , Tsui Chileung
Published: March 2022

We investigate three cases of metamaterials presented in the literature displaying refractive index with one or more discontinuities along the frequency spectrum. We reproduce the numerical simulations of these metamaterials and compare our simulations to each reported case. For each case, we perform a geometrical investigation of each metamaterial’s refractive index by mean of a numerical simulation of a prism made of the reported metamaterials upon which is incident a plane electromagnetic wave. Such investigation allows us to infirm or confirm negative refraction at resonance frequency. Finally, we carry a numerical and theoretical investigation of this discontinuity and show that, as the refractive index crosses a discontinuity, while the topology of the effective wave has changed within the metamaterial, the dynamics of the phases remain unchanged at any time at the metamaterial's boundaries.
Designing siRNA/chitosan-methacrylate complex nanolipogel for prolonged gene silencing effects
Authors: Cao Ye , Tan Yang Fei , Wong Yee Shan , Aminuddin Muhammad , Ramya Bhuthalingam , Liew Melvin Wen Jie , Liu Jiaxin , Venkatraman Subbu S.
Published: March 2022

Despite immense revolutionary therapeutics potential, sustaining release of active small interfering RNA (siRNA) remains an arduous challenge. The development of nanoparticles with siRNA sustained release capabilities provides an avenue to enhance the therapeutic efficacy of gene-based therapy. Herein, we present a new system based on the encapsulation of siRNA/chitosan-methacrylate (CMA) complexes into liposomes to form UV crosslinkable Nanolipogels (NLGs) with sustained siRNA-release properties in vitro. We demonstrated that the CMA nanogel in NLGs can enhance the encapsulation efficiency of siRNA and provide sustained release of siRNA up to 28 days. To understand the particle mechanism of cellular entry, multiple endocytic inhibitors have been used to investigate its endocytosis pathways. The study saw positively charged NLGs entering cells via multiple endocytosis pathways, facilitating endosomal escape and slowly releasing siRNA into the cytoplasm. Transfection experiments confirmed that the crosslinked NLG delivery system provides effective transfection and prolonged silencing effect up to 14 days in cell cultures. We expect that this sustained-release siRNA NLG platform would be of interest in both fundamental biological studies and in clinical applications to extend the use of siRNA-based therapies.
Long-read sequencing for identification of insertion sites in large transposon mutant libraries
Authors: Yasir Muhammad , Turner A. Keith , Lott Martin , Rudder Steven , Baker David , Bastkowski Sarah , Page Andrew J. , Webber Mark A. , Charles Ian G.
Published: March 2022

Transposon insertion site sequencing (TIS) is a powerful method for associating genotype to phenotype. However, all TIS methods described to date use short nucleotide sequence reads which cannot uniquely determine the locations of transposon insertions within repeating genomic sequences where the repeat units are longer than the sequence read length. To overcome this limitation, we have developed a TIS method using Oxford Nanopore sequencing technology that generates and uses long nucleotide sequence reads; we have called this method LoRTIS (Long-Read Transposon Insertion-site Sequencing). LoRTIS enabled the unique localisation of transposon insertion sites within long repetitive genetic elements of E. coli, such as the transposase genes of insertion sequences and copies of the ~ 5 kb ribosomal RNA operon. We demonstrate that LoRTIS is reproducible, gives comparable results to short-read TIS methods for essential genes, and better resolution around repeat elements. The Oxford Nanopore sequencing device that we used is cost-effective, small and easily portable. Thus, LoRTIS is an efficient means of uniquely identifying transposon insertion sites within long repetitive genetic elements and can be easily transported to, and used in, laboratories that lack access to expensive DNA sequencing facilities.