bluuebunny/crossref_metadata_2025 huggingface dataset:
WETTING AND DRYING RESISTANCE OF LIME-STABILIZED EXPANSIVE SOILS MODIFIED WITH NANO-ALUMINA
Authors:   Sri Sivasubramaniya Nadar College of Engineering, Department of Civil Engineering, James Jijo , Sivapriya S V ,   Sri Sivasubramaniya Nadar College of Engineering, Department of Civil Engineering, Ali Sajid ,   Sri Sivasubramaniya Nadar College of Engineering, Department of Civil Engineering, Madhu T R , Singh Basudev ,   Sri Sivasubramaniya Nadar College of Engineering, Department of Civil Engineering
Published: August 2021

Weak soil at construction sites necessitates ground improvement. Chemical stabilization is typically carried out using either lime or cement. The primary objective of this study was to assess the strength and durability of lime-stabilized soils modified with nano-alumina (NA). This study adopted the scientifically established initial consumption of lime (ICL) content for soil stabilization. In addition, nano-alumina was added in varying percentages as an auxiliary additive. It was observed that 0.5 % of nano-alumina was optimal with respect to the ICL for maximizing the soil stabilization. The stabilized soils were cured for 0, 7, 14, and 28 days. Post-curing testing revealed that the strength increased sixfold for the optimal combination, compared with the virgin soil. To understand the durability behavior of the optimal combination, the stabilized soil specimens were subjected to wetting and drying cycles after 28 days of curing. The optimal combination was nearly as durable as that of the lime-stabilized soil subjected to five cycles of wetting and drying.
Impact of the Kerr effect on FM-to-AM conversion in high-power lasers
Authors: Penninckx Denis , Montant Sébastien , Luce Jacques , Bordenave Édouard , Boursier Élodie , Rouyer Claude
Published: August 2021

In order to smooth the focal spot of high-power energetic lasers, pulses are phase-modulated. However, due to propagation impairments, phase modulation is partly converted into power modulation. This is called frequency modulation to amplitude modulation (FM-to-AM conversion). This effect may increase laser damage and thus increase operating costs. For the first time, to the best of our knowledge, we have studied the impact of the Kerr effect in this process. We have shown that when the Kerr effect is followed by a dispersive transfer function, a dramatic increase of FM-to-AM conversion may occur for a particular kind of FM-to-AM conversion that we have named “anomalous.” Hence, we should remove or compensate for one of the items of the sequence: phase modulation, anomalous FM-to-AM conversion, Kerr effect, or the dispersive function. We have assessed all these solutions, and we have found an efficient inspection method to avoid anomalous FM-to-AM conversion.
Theoretical versus empirical measures of retinal magnification for scaling AOSLO images
Authors: Heitkotter H. , Salmon A. E. , Linderman R. E. , Porter J. , Carroll J.
Published: August 2021

The adaptive optics scanning light ophthalmoscope (AOSLO) allows cellular resolution imaging of the living retina. The accuracy of many quantitative measurements made from these images requires accurate estimates of the lateral scale of the images. Here, we used trial lenses, which are known to affect the relative magnification of the retinal image, to compare empirical measures of image scale with theoretical estimates from a four-surface optical model. The theoretical optical model overestimated the empirically determined change in image scale in 70% of the subjects examined, albeit to varying degrees. While the origin for the differences between subjects is not known, residual accommodation during imaging likely contributes to this variability in retinal magnification. These data provide an opportunity to derive improved lateral scaling error estimates for structural metrics extracted from AOSLO retinal images.
Lossless dielectric metasurface with giant intrinsic chirality for terahertz wave
Authors: Li Jie , Li Jitao , Zheng Chenglong , Yang Yue , Yue Zhen , Hao Xuanruo , Zhao Hongliang , Li Fuyu , Tang Tingting , Wu Liang , Li Jining , Zhang Yating , Yao Jianquan
Published: August 2021

It is difficult for single-layer metal metasurfaces to excite in-plane component of magnetic dipole moment, so achieving giant intrinsic optical chirality remains challenging. Fortunately, displacement current in dielectric metasurfaces can form the in-plane magnetic moment which is not orthogonal to the electric dipole moment and forms intrinsic chirality. Here, we show a lossless all-silicon metasurface which achieves giant intrinsic chirality in terahertz band. The leaky waveguide mode in the chiral silicon pillars simultaneously excite the in-plane electric and magnetic dipole moments, which triggers the spin-selected backward electromagnetic radiation, and then realizes the chiral response. The theoretical value of circular dichroism in the transmission spectrum reaches 69.4%, and the measured one is 43%. Based on the photoconductivity effect of the silicon metasurface, we demonstrate optical modulation of the intrinsic chirality using near-infrared continuous wave. In addition, by arranging the two kinds of meta-atoms which are enantiomers, we show the spin-dependent and tunable near-field image display. This simple-prepared all-silicon metasurface provides a new idea for the design of terahertz chiral meta-devices, and it is expected to be applied in the fields of terahertz polarization imaging or spectral detection.
Simple way to fabricate orderly arranged nanostructure arrays on diamond utilizing metal dewetting effect
Authors: Zhu Tian-Fei , Liang Yan , Liu Zhangcheng , Wang Yan-Feng , Shao Guo-Qing , Wen Feng , Min Tai , Wang Hong-Xing
Published: August 2021

We introduce a simple method with thermal annealing round gold disk for agglomeration to fabricate orderly arranged nanostructure arrays on diamond for single photon source applications. In the annealing process, the dependence of gold sphere size on disk thickness and diameter was investigated, showing that gold sphere diameter was decreased with decreasing gold disk thickness or diameter. The condition parameters of ICP etch were adjusted to obtain different nanostructure morphologies on diamond. The collection efficiency of nitrogen-vacancy (NV) center embedded in nanostructure as-fabricated could reach to 53.56% compared with that of 19.10% in planar case with the same simulation method.
Diffuse reflection in periodic arrayed disk metasurfaces
Authors: Zhang Tieyan , Yu Jiachen , Wulan Qiqige , Li Zhe , Liu Zhijun
Published: August 2021

Metamaterials of metal-insulator-metal structures represent effective ways in manipulating light absorbance for photodetection, sensing, and energy harvesting etc. Most of the time, specular reflection has been used in characterizing resonances of metamaterials without considering diffuse scattering from their periodic subwavelength units. In this paper, we investigate diffuse reflection in metasurfaces made of periodic metallic disks in the mid-infrared region. Integrating sphere-based spectral measurements indicate that diffuse reflection is dominated by grating diffractions, which cause diffuse scattering in a spectral region with wavelengths less than that of the first order Rayleigh anomaly. The diffuse reflection is greatly enhanced by the metasurface resonance and exhibits a general increase towards shorter wavelengths, which not only causes a significant difference in evaluating the metamaterial resonant absorption efficiency but also a small blue-shift of the resonance frequency. These findings are helpful for designing and analyzing metamaterial resonant properties when diffuse scattering is taken into account.
Actively tunable multi-band terahertz perfect absorber due to the hybrid strong coupling in the multilayer structure
Authors: Zhang Kun , Xia Feng , Li Shixia , Liu Yan , Kong Weijin
Published: August 2021

In this work, we propose a multi-band terahertz perfect absorber employing the topological photonic crystal combined with VO2 and graphene. The hybrid strong coupling among the topological photonic state, the Tamm plasmon polaritons excited around the interfaces of VO2 and graphene results in the three perfect absorption bands. Benefiting from the reversible insulator-metal phase transition of VO2 and the tunable Fermi level of graphene, it can actively switch among no absorption, single-band, dual-band and multi-band absorptions around 1THz, with the absorption frequencies tunable as well. Besides, the absorption bands are sensitive to the incident angle in almost the same dispersion rate, with high absorptions in a large angle range. Moreover, the splitting frequencies between the adjacent absorption peaks strongly depend on the pair number of the alternating multilayers. Apart from the three absorption bands, there are still many absorption peaks in the large frequency range resulting from the standing waves, including other 7 peaks above 0.9 between 0.83THz and 1.55THz. Such a tunable multi-band absorber with multiple modulation methods may find extended applications in active integrated terahertz devices.
Active speckle deflectometry based on 3D digital image correlation
Authors: Zhang Xinwei , Li Dahai , Wang Ruiyang
Published: August 2021

A method based on 3D digital image correlation (DIC) to measure the shape of specular surface is proposed. The proposed active speckle deflectometry (ASD) utilizes a stereo-camera system to monitor the liquid crystal display (LCD), which is deliberately moved during the measurement. Another testing camera (TC) is used to capture the single-shot speckle pattern displayed on the LCD screen after reflection by the test surface. With this proposal, the movement of the LCD screen can be arbitrary as long as the TC can capture the reflection of speckle pattern. The distance as well as the direction of the movement is not required to be known. The coordinates of the point source are determined by applying the 3D DIC technique with the monitoring stereo-cameras (MSC) before and after the movement of the LCD screen, then the slope and surface shape are obtained. The measurement accuracy of this method is evaluated by measuring a flat glass with a diameter of about 80 mm, compared with the measurement results of interferometer, the shape measurement difference is 0.278um in root mean square (RMS). The shape of two wafers is also measured, and the measurement results are compared to that of the traditional phase measuring deflectometry (PMD). ASD has the advantages of fast measurement, low cost, arbitrary LCD movement, tolerance for the out-of-plane shape of the LCD screen. It provides a new method for specular surface measurement.
Efficient and wavelength-dependent directional launching of a nondiffracting surface plasmon polariton beam device
Authors: Hu Hanmin , Qin Yulu , Ji Boyu , Lang Peng , Song Xiaowei , Lin Jingquan
Published: August 2021

The high-efficiency excitation and dynamic manipulation of the nondiffracting surface plasmon polariton (SPP) beam are important prerequisites for practical applications including the next-generation on-chip devices, near field optical trapping, and micromanipulation. Here we proposed two kinds of high-efficiency coupling and wavelength-dependent nondiffracting SPP beam unidirectional devices, which can generate and manipulate Bessel-like SPP beam or SPP Bottle beam, respectively. Different from the conventional groove or ridge structure that equally split SPP power to propagate from the boundary to both sides, the compact coupling element directs all of the SPP power of the matched wavelength to one side, resulting in higher collecting efficiency. Besides, as the wavelength of the incident light is changed, the generated Bessel-like SPP beam or SPP Bottle beam can be directionally excited on one side of the device. The design of the proposed devices provides a new means for constructing plasmonic devices with wavelength-dependent dynamic manipulation of nondiffracting SPP beams and has potential applications in on-chip interconnect circuits and near-field optical trapping.
Global and national trends, gaps, and opportunities in documenting and monitoring species distributions
Authors: Oliver Ruth Y. , Meyer Carsten , Ranipeta Ajay , Winner Kevin , Jetz Walter
Published: August 2021

Conserving and managing biodiversity in the face of ongoing global change requires sufficient evidence to assess status and trends of species distributions. Here, we propose novel indicators of biodiversity data coverage and sampling effectiveness and analyze national trajectories in closing spatiotemporal knowledge gaps for terrestrial vertebrates (1950 to 2019). Despite a rapid rise in data coverage, particularly in the last 2 decades, strong geographic and taxonomic biases persist. For some taxa and regions, a tremendous growth in records failed to directly translate into newfound knowledge due to a sharp decline in sampling effectiveness. However, we found that a nation’s coverage was stronger for species for which it holds greater stewardship. As countries under the post-2020 Global Biodiversity Framework renew their commitments to an improved, rigorous biodiversity knowledge base, our findings highlight opportunities for international collaboration to close critical information gaps.
Evaluation and comparison of multi-omics data integration methods for cancer subtyping
Authors: Duan Ran , Gao Lin , Gao Yong , Hu Yuxuan , Xu Han , Huang Mingfeng , Song Kuo , Wang Hongda , Dong Yongqiang , Jiang Chaoqun , Zhang Chenxing , Jia Songwei
Published: August 2021

Computational integrative analysis has become a significant approach in the data-driven exploration of biological problems. Many integration methods for cancer subtyping have been proposed, but evaluating these methods has become a complicated problem due to the lack of gold standards. Moreover, questions of practical importance remain to be addressed regarding the impact of selecting appropriate data types and combinations on the performance of integrative studies. Here, we constructed three classes of benchmarking datasets of nine cancers in TCGA by considering all the eleven combinations of four multi-omics data types. Using these datasets, we conducted a comprehensive evaluation of ten representative integration methods for cancer subtyping in terms of accuracy measured by combining both clustering accuracy and clinical significance, robustness, and computational efficiency. We subsequently investigated the influence of different omics data on cancer subtyping and the effectiveness of their combinations. Refuting the widely held intuition that incorporating more types of omics data always produces better results, our analyses showed that there are situations where integrating more omics data negatively impacts the performance of integration methods. Our analyses also suggested several effective combinations for most cancers under our studies, which may be of particular interest to researchers in omics data analysis.
A computational method for identifying an optimal combination of existing drugs to repair the action potentials of SQT1 ventricular myocytes
Authors: Jæger Karoline Horgmo , Edwards Andrew G. , Giles Wayne R. , Tveito Aslak
Published: August 2021

Mutations are known to cause perturbations in essential functional features of integral membrane proteins, including ion channels. Even restricted or point mutations can result in substantially changed properties of ion currents. The additive effect of these alterations for a specific ion channel can result in significantly changed properties of the action potential (AP). Both AP shortening and AP prolongation can result from known mutations, and the consequences can be life-threatening. Here, we present a computational method for identifying new drugs utilizing combinations of existing drugs. Based on the knowledge of theoretical effects of existing drugs on individual ion currents, our aim is to compute optimal combinations that can ‘repair’ the mutant AP waveforms so that the baseline AP-properties are restored. More specifically, we compute optimal, combined, drug concentrations such that the waveforms of the transmembrane potential and the cytosolic calcium concentration of the mutant cardiomyocytes (CMs) becomes as similar as possible to their wild type counterparts after the drug has been applied. In order to demonstrate the utility of this method, we address the question of computing an optimal drug for the short QT syndrome type 1 (SQT1). For the SQT1 mutation N588K, there are available data sets that describe the effect of various drugs on the mutated K+channel. These published findings are the basis for our computational analysis which can identify optimal compounds in the sense that the AP of the mutant CMs resembles essential biomarkers of the wild type CMs. Using recently developed insights regarding electrophysiological properties among myocytes from different species, we compute optimal drug combinations for hiPSC-CMs, rabbit ventricular CMs and adult human ventricular CMs with the SQT1 mutation. Since the ‘composition’ of ion channels that form the AP is different for the three types of myocytes under consideration, so is the composition of the optimal drug.
Connection of core and tail Mediator modules restrains transcription from TFIID-dependent promoters
Authors: Saleh Moustafa M. , Jeronimo Célia , Robert François , Zentner Gabriel E.
Published: August 2021

The Mediator coactivator complex is divided into four modules: head, middle, tail, and kinase. Deletion of the architectural subunit Med16 separates core Mediator (cMed), comprising the head, middle, and scaffold (Med14), from the tail. However, the direct global effects of tail/cMed disconnection are unclear. We find that rapid depletion of Med16 downregulates genes that require the SAGA complex for full expression, consistent with their reported tail dependence, but also moderately overactivates TFIID-dependent genes in a manner partly dependent on the separated tail, which remains associated with upstream activating sequences. Suppression of TBP dynamics via removal of the Mot1 ATPase partially restores normal transcriptional activity to Med16-depleted cells, suggesting that cMed/tail separation results in an imbalance in the levels of PIC formation at SAGA-requiring and TFIID-dependent genes. We propose that the preferential regulation of SAGA-requiring genes by tailed Mediator helps maintain a proper balance of transcription between these genes and those more dependent on TFIID.
The native cistrome and sequence motif families of the maize ear
Authors: Savadel Savannah D. , Hartwig Thomas , Turpin Zachary M. , Vera Daniel L. , Lung Pei-Yau , Sui Xin , Blank Max , Frommer Wolf B. , Dennis Jonathan H. , Zhang Jinfeng , Bass Hank W.
Published: August 2021

Elucidating the transcriptional regulatory networks that underlie growth and development requires robust ways to define the complete set of transcription factor (TF) binding sites. Although TF-binding sites are known to be generally located within accessible chromatin regions (ACRs), pinpointing these DNA regulatory elements globally remains challenging. Current approaches primarily identify binding sites for a single TF (e.g. ChIP-seq), or globally detect ACRs but lack the resolution to consistently define TF-binding sites (e.g. DNAse-seq, ATAC-seq). To address this challenge, we developed MNase-defined cistrome-Occupancy Analysis (MOA-seq), a high-resolution (< 30 bp), high-throughput, and genome-wide strategy to globally identify putative TF-binding sites within ACRs. We used MOA-seq on developing maize ears as a proof of concept, able to define a cistrome of 145,000 MOA footprints (MFs). While a substantial majority (76%) of the known ATAC-seq ACRs intersected with the MFs, only a minority of MFs overlapped with the ATAC peaks, indicating that the majority of MFs were novel and not detected by ATAC-seq. MFs were associated with promoters and significantly enriched for TF-binding and long-range chromatin interaction sites, including for the well-characterized FASCIATED EAR4, KNOTTED1, and TEOSINTE BRANCHED1. Importantly, the MOA-seq strategy improved the spatial resolution of TF-binding prediction and allowed us to identify 215 motif families collectively distributed over more than 100,000 non-overlapping, putatively-occupied binding sites across the genome. Our study presents a simple, efficient, and high-resolution approach to identify putative TF footprints and binding motifs genome-wide, to ultimately define a native cistrome atlas.
Mitochondrial fission, integrity and completion of mitophagy require separable functions of Vps13D in Drosophila neurons
Authors: Insolera Ryan , Lőrincz Péter , Wishnie Alec J. , Juhász Gábor , Collins Catherine A.
Published: August 2021

A healthy population of mitochondria, maintained by proper fission, fusion, and degradation, is critical for the long-term survival and function of neurons. Here, our discovery of mitophagy intermediates in fission-impairedDrosophilaneurons brings new perspective into the relationship between mitochondrial fission and mitophagy. Neurons lacking either the ataxia disease gene Vps13D or the dynamin related protein Drp1 contain enlarged mitochondria that are engaged with autophagy machinery and also lack matrix components. Reporter assays combined with genetic studies imply that mitophagy both initiates and is completed in Drp1 impaired neurons, but fails to complete in Vps13D impaired neurons, which accumulate compromised mitochondria within stalled mito-phagophores. Our findings imply that in fission-defective neurons, mitophagy becomes induced, and that the lipid channel containing protein Vps13D has separable functions in mitochondrial fission and phagophore elongation.
The global burden of chromoblastomycosis
Authors: Santos Daniel Wagner C. L. , de Azevedo Conceição de Maria Pedrozo e Silva , Vicente Vania Aparecida , Queiroz-Telles Flávio , Rodrigues Anderson Messias , de Hoog G. Sybren , Denning David W. , Colombo Arnaldo Lopes
Published: August 2021

Background

Chromoblastomycosis (CBM), represents one of the primary implantation mycoses caused by melanized fungi widely found in nature. It is characterized as a Neglected Tropical Disease (NTD) and mainly affects populations living in poverty with significant morbidity, including stigma and discrimination.

Methods and findings

In order to estimate the global burden of CBM, we retrospectively reviewed the published literature from 1914 to 2020. Over the 106-year period, a total of 7,740 patients with CBM were identified on all continents except Antarctica. Most of the cases were reported from South America (2,619 cases), followed by Africa (1,875 cases), Central America and Mexico (1,628 cases), Asia (1,390 cases), Oceania (168 cases), Europe (35 cases), and USA and Canada (25 cases). We described 4,022 (81.7%) male and 896 (18.3%) female patients, with the median age of 52.5 years. The average time between the onset of the first lesion and CBM diagnosis was 9.2 years (range between 1 month to 50 years). The main sites involved were the lower limbs (56.7%), followed by the upper limbs (19.9%), head and neck (2.9%), and trunk (2.4%). Itching and pain were reported by 21.5% and 11%, respectively. Malignant transformation was described in 22 cases. A total of 3,817 fungal isolates were cultured, being 3,089 (80.9%) Fonsecaea spp., 552 (14.5%) Cladophialophora spp., and 56 Phialophora spp. (1.5%).

Conclusions and significance

This review represents our current knowledge on the burden of CBM world-wide. The global incidence remains unclear and local epidemiological studies are required to improve these data, especially in Africa, Asia, and Latin America. The recognition of CBM as NTD emphasizes the need for public health efforts to promote support for all local governments interested in developing specific policies and actions for preventing, diagnosing and assisting patients.
Individual and community factors determining delayed leprosy case detection: A systematic review
Authors: Dharmawan Yudhy , Fuady Ahmad , Korfage Ida , Richardus Jan Hendrik
Published: August 2021

Background

The number of new leprosy cases is declining globally, but the disability caused by leprosy remains an important disease burden. The chance of disability is increased by delayed case detection. This review focusses on the individual and community determinants of delayed leprosy case detection.

Methods

This study was conducted according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). The study protocol is registered in PROSPERO (code: CRD42020189274). To identify determinants of delayed detection, data was collected from five electronic databases: Embase.com, Medline All Ovid, Web of Science, Cochrane CENTRAL, and the WHO Global Health Library.

Results

We included 27 papers from 4315 records assessed. They originated in twelve countries, had been published between January 1, 2000, and January 31, 2021, and described the factors related to delayed leprosy case detection, the duration of the delayed case, and the percentage of Grade 2 Disability (G2D). The median delay in detection ranged from 12 to 36 months, the mean delay ranged from 11.5 to 64.1 months, and the percentage of G2D ranged from 5.6 to 43.2%. Health-service-seeking behavior was the most common factor associated with delayed detection. The most common individual factors were older age, being male, having a lower disease-symptom perception, having multibacillary leprosy, and lack of knowledge. The most common socioeconomic factors were living in a rural area, performing agricultural labor, and being unemployed. Stigma was the most common social and community factor.

Conclusions

Delayed leprosy case detection is clearly correlated with increased disability and should therefore be a priority of leprosy programs. Interventions should focus on determinants of delayed case detection such as health-service-seeking behavior, and should consider relevant individual, socioeconomic, and community factors, including stigmatization. Further study is required of the health service-related factors contributing to delay.
Cost-effectiveness and budget impact analyses of dengue vaccination in Indonesia
Authors: Suwantika Auliya Abdurrohim , Supadmi Woro , Ali Mohammad , Abdulah Rizky
Published: August 2021

Despite the fact that the incidence and mortality rates due to dengue virus (DENV) infection in Indonesia are relatively high, dengue vaccination has not yet been introduced. This study aimed to analyse the cost-effectiveness and the budget impact of dengue vaccination in Indonesia by taking the potential of pre-vaccination screening into account. An age-structured decision tree model was developed to assess the cost-effectiveness value by applying a single cohort of 4,710,100 children that was followed-up in a 10-year time horizon within a 1-year analytical cycle. The budget impact was analysed in a 5-year period (2020–2024) by considering provinces’ readiness to introduce dengue vaccine and their incidence rate of DENV infection in the last 10 years. Vaccination that was coupled with pre-vaccination screening would reduce dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) by 188,142, 148,089 and 426 cases, respectively. It would save treatment cost at $23,433,695 and $14,091,642 from the healthcare and payer perspective, respectively. The incremental cost-effectiveness ratios (ICERs) would be $5,733 and $5,791 per quality-adjusted-life-year (QALY) gained from both perspectives. The most influential parameters affecting the ICERs were probability of DENV infection, vaccine efficacy, under-reporting factor, vaccine price, case fatality rate and screening cost. It can be concluded that dengue vaccination and pre-vaccination screening would be cost-effective to be implemented in Indonesia. Nevertheless, it seems unaffordable to be implemented since the total required cost for the nationwide vaccination would be 94.44% of routine immunization budget.
Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22
Authors: Schnepf Daniel , Hernandez Pedro , Mahlakõiv Tanel , Crotta Stefania , Sullender Meagan E. , Peterson Stefan T. , Ohnemus Annette , Michiels Camille , Gentle Ian , Dumoutier Laure , Reis Celso A. , Diefenbach Andreas , Wack Andreas , Baldridge Megan T. , Staeheli Peter
Published: August 2021

The commensal microbiota regulates susceptibility to enteric pathogens by fine-tuning mucosal innate immune responses, but how susceptibility to enteric viruses is shaped by the microbiota remains incompletely understood. Past reports have indicated that commensal bacteria may either promote or repress rotavirus replication in the small intestine of mice. We now report that rotavirus replicated more efficiently in the intestines of germ-free and antibiotic-treated mice compared to animals with an unmodified microbiota. Antibiotic treatment also facilitated rotavirus replication in type I and type III interferon (IFN) receptor-deficient mice, revealing IFN-independent proviral effects. Expression of interleukin-22 (IL-22) was strongly diminished in the intestine of antibiotic-treated mice. Treatment with exogenous IL-22 blocked rotavirus replication in microbiota-depleted wild-type and Stat1-/- mice, demonstrating that the antiviral effect of IL-22 in animals with altered microbiome is not dependent on IFN signaling. In antibiotic-treated animals, IL-22-induced a specific set of genes including Fut2, encoding fucosyl-transferase 2 that participates in the biosynthesis of fucosylated glycans which can mediate rotavirus binding. Interestingly, IL-22 also blocked rotavirus replication in antibiotic-treated Fut2-/- mice. Furthermore, IL-22 inhibited rotavirus replication in antibiotic-treated mice lacking key molecules of the necroptosis or pyroptosis pathways of programmed cell death. Taken together, our results demonstrate that IL-22 determines rotavirus susceptibility of antibiotic-treated mice, yet the IL-22-induced effector molecules conferring rotavirus resistance remain elusive.
The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study
Authors: Milic Jovana , Banchelli Federico , Meschiari Marianna , Franceschini Erica , Ciusa Giacomo , Gozzi Licia , Volpi Sara , Faltoni Matteo , Franceschi Giacomo , Iadisernia Vittorio , Yaacoub Dina , Dolci Giovanni , Bacca Erica , Rogati Carlotta , Tutone Marco , Burastero Giulia , Raimondi Alessandro , Menozzi Marianna , Cuomo Gianluca , Corradi Luca , Orlando Gabriella , Santoro Antonella , Digaetano Margherita , Puzzolante Cinzia , Carli Federica , Bedini Andrea , Busani Stefano , Girardis Massimo , Cossarizza Andrea , Miglio Rossella , Mussini Cristina , Guaraldi Giovanni , D’Amico Roberto
Published: August 2021

Background

The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery.

Methods

In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery.

Results

Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2–5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1–0.7) or in OT (HR = 0.1, 95% CI = 0.0–0.8) treated with tocilizumab.

Conclusion

To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.
easyXpress: An R package to analyze and visualize high-throughput C. elegans microscopy data generated using CellProfiler
Authors: Nyaanga Joy , Crombie Timothy A. , Widmayer Samuel J. , Andersen Erik C.
Published: August 2021

High-throughput imaging techniques have become widespread in many fields of biology. These powerful platforms generate large quantities of data that can be difficult to process and visualize efficiently using existing tools. We developed easyXpress to process and review C. elegans high-throughput microscopy data in the R environment. The package provides a logical workflow for the reading, analysis, and visualization of data generated using CellProfiler’s WormToolbox. We equipped easyXpress with powerful functions to customize the filtering of noise in data, specifically by identifying and removing objects that deviate from expected animal measurements. This flexibility in data filtering allows users to optimize their analysis pipeline to match their needs. In addition, easyXpress includes tools for generating detailed visualizations, allowing the user to interactively compare summary statistics across wells and plates with ease. Researchers studying C. elegans benefit from this streamlined and extensible package as it is complementary to CellProfiler and leverages the R environment to rapidly process and analyze large high-throughput imaging datasets.
Factors hindering integration of care for non-communicable diseases within HIV care services in Dar es Salaam, Tanzania: The perspectives of health workers and people living with HIV
Authors: Haruna Tausi , Somba Magreat , Siril Hellen , Mahiti Gladys , August Francis , Minja Anna , Urassa David , Tarimo Edith , Mugusi Ferdinand
Published: August 2021

Background

Global mortality attributable to non-communicable diseases (NCDs) occurs in more than 36 million people annually with 80% of these deaths occurring in resource limited countries. Among people living with HIV and AIDS (PLHA) studies have reported higher prevalence’s of NCDs compared to the general population but most studies do report a narrow range of NCDs commonly hypertension, diabetes and neoplasms and not all. In addition, there is limited reporting, integration of systematic screening and treatment for all NCDs among PLHA attending care, suggesting the NCD burden among PLHA is likely an underestimate. Little is known about factors facilitating or hindering integration of the care and treatment of NCDs within HIV care and treatment clinics (CTCs) in Tanzania.

Objective

To explore the perceptions of PLHA and health workers on factors facilitate or hinder the recognition and integration of care for NCDs within CTCs in Dar es Salaam.

Methods

Inductive content analysis of transcripts from 41 in-depth interviews were conducted with 5 CTC managers (CTC Managers), 9 healthcare providers (DHCP) and 27 people living with HIV (PLHA) attending CTCs and with co-morbid NCDs.

Results

Four themes emerged; the current situation of services available for care and treatment of NCDs among PLHA in CTCs, experiences of PLHA with co-morbid NCDs with access to care and treatment services for NCDs, facilitators of integrating care and treatment of NCDs within CTCs and perceived barriers for accessing and integration of care and treatment of NCDs within CTCs.

Conclusions

There was a positive attitude among PLHA and healthcare workers towards integration of NCD services within CTC services. This was enhanced by perceived benefits inherent to the services. Factors hindering integration of NCD care and services included; limited and inconsistent supplies such as screening equipment, medications; insufficient awareness of NCDs within PLHA; lack of adequate training of healthcare workers on management of NCD and treatment costs and payment systems.
Potency of propofol for inducing loss of consciousness in end-stage kidney disease patients
Authors: Jun Mi Roung , Kim Mun Gyu , Han Ki Seob , Park Ji Eun , Cho Ho Bum , Park Sun Young , Song Sanghoon , Yoo Jae Hwa , Chung Ji Won , Kim Sang Ho
Published: August 2021

It can be difficult for anesthesiologists to determine the optimal dose of propofol for end-stage kidney disease (ESKD) patients due to changes in drug disposition. The purpose of this study was to evaluate the potency of propofol for inducing loss of consciousness in ESKD patients. Patients with normal kidney function (Control group, n = 15), those with ESKD (ESKD group, n = 15), and those with ESKD undergoing cervical epidural anesthesia (ESKD-CEB group, n = 15) were administered propofol by target-controlled infusion (TCI) using the Schneider model. The effect-site concentration (Ce) of propofol started at 0.5 μg/ml and increased in increments of 0.5 μg/ml until the patient did not respond to verbal commands. The relationship between the probability (P) of loss of consciousness and the Ce of propofol was analyzed in each group using logistic regression. The Ce values of propofol at the time of loss of consciousness were 4.3 ± 0.9, 3.7 ± 0.9, and 3.3 ± 1.0 μg/ml for the Control, ESKD, and ESKD-CEB* groups, respectively (*significant difference vs. control, P < 0.05). The estimated Ce50 values for lost ability to respond to verbal command were 4.56, 3.75, and 3.21 μg/ml for the Control, ESKD, and ESKD-CEB groups, respectively. In conclusion, when inducing anesthesia in ESKD patients, we recommend using an initial dose similar to that of patients with normal kidney function, or rather starting with a lower dose.
Preliminary model assessing the cost-effectiveness of preoperative chlorhexidine mouthwash at reducing postoperative pneumonia among abdominal surgery patients in South Africa
Authors: Kachapila Mwayi , Ademuyiwa Adesoji O. , Biccard Bruce M. , Ghosh Dhruva N. , Glasbey James , Monahan Mark , Moore Rachel , Morton Dion G. , Oppong Raymond , Pearse Rupert , Roberts Tracy E. ,   NIHR Global Health Research Unit on Global Surgery,   ASOS Investigators,   STARSurg Collaborative
Published: August 2021

Background

Pneumonia is a common and severe complication of abdominal surgery, it is associated with increased length of hospital stay, healthcare costs, and mortality. Further, pulmonary complication rates have risen during the SARS-CoV-2 pandemic. This study explored the potential cost-effectiveness of administering preoperative chlorhexidine mouthwash versus no-mouthwash at reducing postoperative pneumonia among abdominal surgery patients.

Methods

A decision analytic model taking the South African healthcare provider perspective was constructed to compare costs and benefits of mouthwash versus no-mouthwash-surgery at 30 days after abdominal surgery. We assumed two scenarios: (i) the absence of COVID-19; (ii) the presence of COVID-19. Input parameters were collected from published literature including prospective cohort studies and expert opinion. Effectiveness was measured as proportion of pneumonia patients. Deterministic and probabilistic sensitivity analyses were performed to assess the impact of parameter uncertainties. The results of the probabilistic sensitivity analysis were presented using cost-effectiveness planes and cost-effectiveness acceptability curves.

Results

In the absence of COVID-19, mouthwash had lower average costs compared to no-mouthwash-surgery, $3,675 (R 63,770) versus $3,958 (R 68,683), and lower proportion of pneumonia patients, 0.029 versus 0.042 (dominance of mouthwash intervention). In the presence of COVID-19, the increase in pneumonia rate due to COVID-19, made mouthwash more dominant as it was more beneficial to reduce pneumonia patients through administering mouthwash. The cost-effectiveness acceptability curves shown that mouthwash surgery is likely to be cost-effective between $0 (R0) and $15,000 (R 260,220) willingness to pay thresholds.

Conclusions

Both the absence and presence of SARS-CoV-2, mouthwash is likely to be cost saving intervention for reducing pneumonia after abdominal surgery. However, the available evidence for the effectiveness of mouthwash was extrapolated from cardiac surgery; there is now an urgent need for a robust clinical trial on the intervention on non-cardiac surgery.
A holistic approach for suppression of COVID-19 spread in workplaces and universities
Authors: Poole Sarah F. , Gronsbell Jessica , Winter Dale , Nickels Stefanie , Levy Roie , Fu Bin , Burq Maximilien , Saeb Sohrab , Edwards Matthew D. , Behr Michael K. , Kumaresan Vignesh , Macalalad Alexander R. , Shah Sneh , Prevost Michelle , Snoad Nigel , Brenner Michael P. , Myers Lance J. , Varghese Paul , Califf Robert M. , Washington Vindell , Lee Vivian S. , Fromer Menachem
Published: August 2021

As society has moved past the initial phase of the COVID-19 crisis that relied on broad-spectrum shutdowns as a stopgap method, industries and institutions have faced the daunting question of how to return to a stabilized state of activities and more fully reopen the economy. A core problem is how to return people to their workplaces and educational institutions in a manner that is safe, ethical, grounded in science, and takes into account the unique factors and needs of each organization and community. In this paper, we introduce an epidemiological model (the “Community-Workplace” model) that accounts for SARS-CoV-2 transmission within the workplace, within the surrounding community, and between them. We use this multi-group deterministic compartmental model to consider various testing strategies that, together with symptom screening, exposure tracking, and nonpharmaceutical interventions (NPI) such as mask wearing and physical distancing, aim to reduce disease spread in the workplace. Our framework is designed to be adaptable to a variety of specific workplace environments to support planning efforts as reopenings continue. Using this model, we consider a number of case studies, including an office workplace, a factory floor, and a university campus. Analysis of these cases illustrates that continuous testing can help a workplace avoid an outbreak by reducing undetected infectiousness even in high-contact environments. We find that a university setting, where individuals spend more time on campus and have a higher contact load, requires more testing to remain safe, compared to a factory or office setting. Under the modeling assumptions, we find that maintaining a prevalence below 3% can be achieved in an office setting by testing its workforce every two weeks, whereas achieving this same goal for a university could require as much as fourfold more testing (i.e., testing the entire campus population twice a week). Our model also simulates the dynamics of reduced spread that result from the introduction of mitigation measures when test results reveal the early stages of a workplace outbreak. We use this to show that a vigilant university that has the ability to quickly react to outbreaks can be justified in implementing testing at the same rate as a lower-risk office workplace. Finally, we quantify the devastating impact that an outbreak in a small-town college could have on the surrounding community, which supports the notion that communities can be better protected by supporting their local places of business in preventing onsite spread of disease.
Norcycloartocarpin targets Akt and suppresses Akt-dependent survival and epithelial-mesenchymal transition in lung cancer cells
Authors: Nonpanya Nongyao , Sanookpan Kittipong , Joyjamras Keerati , Wichadakul Duangdao , Sritularak Boonchoo , Chaotham Chatchai , Chanvorachote Pithi
Published: August 2021

In searching for novel targeted therapeutic agents for lung cancer treatment, norcycloartocarpin fromArtocarpus gomezianuswas reported in this study to promisingly interacted with Akt and exerted the apoptosis induction and epithelial-to-mesenchymal transition suppression. Selective cytotoxic profile of norcycloartocarpin was evidenced with approximately 2-fold higher IC50in normal dermal papilla cells (DPCs) compared with human lung cancer A549, H460, H23, and H292 cells. We found that norcycloartocarpin suppressed anchorage-independent growth, cell migration, invasion, filopodia formation, and decreased EMT in a dose-dependent manner at 24 h, which were correlated with reduced protein levels of N-cadherin, Vimentin, Slug, p-FAK, p-Akt, as well as Cdc42. In addition, norcycloartocarpin activated apoptosis caspase cascade associating with restoration of p53, down-regulated Bcl-2 and augmented Bax in A549 and H460 cells. Interestingly, norcycloartocarpin showed potential inhibitory role on protein kinase B (Akt) the up-stream dominant molecule controlling EMT and apoptosis. Computational molecular docking analysis further confirmed that norcycloartocarpin has the best binding affinity of -12.52 kcal/mol with Akt protein at its critical active site. As Akt has recently recognized as an attractive molecular target for therapeutic approaches, these findings support its use as a plant-derived anticancer agent in cancer therapy.
A self-oblique exercise that activates the coordinated activity of abdominal and hip muscles–A pilot study
Authors: Nakai Yuki , Kawada Masayuki , Miyazaki Takasuke , Araki Sota , Takeshita Yasufumi , Kiyama Ryoji
Published: August 2021

The importance of an interaction between trunk stability muscles and hip muscle function has been suggested. However, reported exercises rarely act on the trunk and hip muscles simultaneously. Here, we devised an abdominal oblique and hip muscle exercise, the Self-oblique exercise (SOE). We examined whether SOE activated abdominal and hip muscles in the supine and half-kneeling positions, compared with abdominal crunch (AC) and plank exercises; and whether participants could modulate the exercise load. Participants were 20 healthy males with some sports experience such as football and baseball on average 10.5 ± 4.0 years. Participants applied self-pressure to their right thighs using the contralateral upper limb with 40% or 70% of the maximum force in Supine SOE and Half- kneeling SOE. The following abdominal and hip muscles were measured using surface electromyography: bilateral external obliques (EO), bilateral internal obliques (IO), right rectus abdominis, right gluteus medius (GMed), and right adductor longus (ADD). All evaluated muscle groups showed significant differences between exercises (p < 0.001). Supine SOE-70% showed 80.4% maximal voluntary contraction (MVC) for left EO (p < 0.017), 61.4% MVC for right IO (p < 0.027), 24.3% MVC for GMed (p < 0.002), and 42.4% MVC for ADD (p < 0.004); these were significantly greatest among all exercises. Muscle activity during Supine SOE-70% was greater than that during Supine SOE-40%. Similarly, Half-kneeling SOE-40% promoted abdominal and hip muscle exertion, and showed more significant activity in GMed (p < 0.006) and ADD (p < 0.001) than AC and plank. SOE could activate abdominal and hip muscles depends on the pressure applied by upper limb. Also, SOE allows participants to modulate the exercise load in a self-controlled step by step manner. Modulation of the exercise load is difficult in AC or plank compared to SOE, and AC or plank cannot obtain simultaneous oblique and hip muscle activity. SOE could be practiced anywhere, in various positions, without any tools.