bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of annealing constraint methods on poly(L‐lactic acid) monofilaments for application in stents annealing
Authors: Li Xin , Tian Yuan , Zhang Jing , Cheng Jie , Wu Gensheng , Zhang Yi , Zhao Gutian , Ni Zhonghua
Published: March 2021

Mechanical properties of poly(L‐lactic acid) (PLLA) braided stents are closely related to the performance of the weaving monofilaments. In this study, the PLLA monofilaments were prepared via solid‐state drawing (SSD) method and annealed with different constraint methods. Experimental results show that mechanical properties of fabricated monofilaments have been greatly improved by SSD method. With the constrained annealing method, mechanical properties can be further improved while negative effect is shown with unconstrained annealing method. The physicochemical properties of PLLA monofilaments were further characterized, and it is found that the draw ratio of SSD and annealing method can affect the crystallinity and crystallite size, which can directly influence the mechanical properties of the monofilaments. This work tells that it is necessary to consider collectively the effects of SSD method and annealing method of the monofilaments in order to obtain optimized mechanical properties of the braided stents.
Investigating the criticality of user‐reported issues through their relations with app rating
Authors: Di Sorbo Andrea , Grano Giovanni , Aaron Visaggio Corrado , Panichella Sebastiano
Published: March 2021

App quality impacts user experience and satisfaction. As a consequence, both app ratings and user feedback reported in app reviews are directly influenced by the user‐perceived app quality. Through an empirical study involving 210,517 reviews related to 317 Android apps, in this paper, we experiment with the combined usage of app rating and user reviews analysis (i) to investigate the most important factors influencing the perceived app quality, (ii) focusing on the topics discussed in user review that most relate with app rating. Besides, we investigate whether specific code quality metrics could be monitored to prevent the rising of negative user feedback (i.e., types of user review comments), connected with low ratings. Our study demonstrates that user comments reporting bugs are negatively correlated with the rating, while reviews reportingfeature requests do not. Interestingly, depending on the app category, we observed that different kinds of issues have rather different relationships with the rating and the user‐perceived quality of the app. In particular, we observe that for specific app categories (e.g., communication), some code quality factors have significant relationships with the raising of certain types of feedback, which, in turn, are negatively connected with app ratings.
On the mechanism of three-body adhesive wear in turning
Authors: Svenningsson Inge , Tatar Kourosh
Published: March 2021

The paper reveals a hypothesis regarding the adhesive mechanism in metal cutting and its mechanical dynamics. One steel grade, 34CrNiMo 6, 285 HB, and one set of coatings on the cutting tool are reviewed. The adhesive mechanism is a transient vibration, including a feedback system limited by the plastic deformation in the chip. The vibration shows as a cluster of waves with stochastic duration in time. It starts up again after a stochastic lapse of silence. The cycle frequency is around 12.5 kHz and the internal excitation is twice that frequency, as the cutting speed and feed are 200 m/min and 0.2 mm, respectively. The adhesive frequency and amplitude are influenced by the cutting speed and the current wear status. The adhesion is monitored by the sound waves emanating from vibrations in the chip, the part still in the workpiece.
A qualitative evaluation of a nurse-led pre-operative stoma education program for bladder cancer patients
Authors: Wulff-Burchfield Elizabeth Marie , Potts Maryellen , Glavin Katherine , Mirza Moben
Published: March 2021

Introduction

Radical cystectomy remains the standard of care for muscle-invasive bladder cancer and high-risk non-muscle-invasive bladder cancer. Postoperative ostomy education is common, but patients struggle to maintain self-management practices. A preoperative ostomy education program was developed to meet this need, and we conducted a qualitative study with participating patient-caregiver dyads to evaluate the educational and psychosocial impacts of the program and examine alignment with program objectives.

Materials and methods

A qualitative descriptive study was conducted utilizing a thematic analysis approach. Sixteen patients, eighteen caregivers, and three program educators completed semi-structured interviews from 3 to 18 months post the program. Interviews were audio-recorded and transcribed. Thirteen end-of-course surveys from the initial educational program cohort were transcribed, coded, analyzed; this data was triangulated with patient, caregiver, and educator interviews.

Results

Analysis uncovered three themes: (1) Patient and caregiver motivation to attend the program, (2) attitudes toward this life-changing event, and (3) education. For theme 1, patients and caregivers cited lack of knowledge, fear, and concern about ostomy surgery and care as motivation. For theme 2, there were a variety of attitudes toward the ostomy, ranging from avoidance to acceptance, and a similar breadth of attitudes toward caregiving, with some patients and caregivers describing ongoing dependence and other patients seeking complete independence. For theme 3, the interactive curriculum was determined to be effective, and the patient advocate was cited as the most memorable program component.

Conclusions

A formal preoperative ostomy education program employing an interactive educational approach and featuring a patient advocate can prepare bladder cancer patients and caregivers for ostomy self-management and post-ostomy life.
Classification and seismic fragility assessment of confined masonry school buildings
Authors: Parammal Vatteri Ahsana , D’Ayala Dina
Published: March 2021

School buildings being a critical social infrastructure, assessment of their seismic behaviour is of utmost importance in ensuring safe schooling facilities in locations of high seismicity. This study presents two important aspects in analysing any existing building stock for seismic behaviour: the development of an appropriate taxonomy system and an appropriate analytical method to conduct fragility assessment. A detailed desk study of existing schools’ databases and tailored field investigation in Guwahati, Assam, situated in India’s highest seismic zone, reveal that the majority of school buildings can be categorised within the confined masonry (CM) typology. This study discusses first, the addition to the World Bank promoted Global Library of School Infrastructure taxonomy of the specific category relating to CM as to include the buildings under study, which are non-engineered CM buildings with flexible roofs. Identifying the density of confinement and quality of connections as critical parameters for the seismic response of these buildings, varying seismic design levels are defined in relation to these indicators. Secondly, the paper presents an approach for carrying out nonlinear static pushover analysis of these buildings with flexible diaphragms and elaborates on the criteria adopted for determining the performance drift limits in buildings with varying levels of seismic design. Numerical analysis for the capacity assessment of selected index buildings is carried out using a commercial software that enables nonlinear extreme loading analysis. Different failure mechanisms as a function of the level of confinement are identified and the performance range for three damage states for three index buildings is obtained by using the N2 method. The study shows the influence of both choices of performance indicators and intensity measure on the resulting fragility functions. Given the consistency of the educational building stock in Guwahati, the results can be used for investment on retrofit decision making at regional level.
Steam reforming of ethanol for hydrogen production: influence of catalyst composition (Ni/Al2O3, Ni/Al2O3–CeO2, Ni/Al2O3–ZnO) and process conditions
Authors: Shtyka O. , Dimitrova Z. , Ciesielski R. , Kedziora A. , Mitukiewicz G. , Leyko J. , Maniukewicz W. , Czylkowska A. , Maniecki T.
Published: March 2021

Ethanol steam reforming was studied over Ni supported catalysts. The effects of support (Al2O3, Al2O3–ZnO, and Al2O3–CeO2), metal loading, catalyst activation method, and steam-to-ethanol molar feed ratio were investigated. The properties of catalysts were studied by N2 physisorption, TPD-CO2, X-ray diffraction, and temperature programmed reduction. After activity tests, the catalysts were analyzed by TOC analysis. The catalytic activity measurements showed that the addition either of ZnO SSor CeO2 to alumina enhances both ethanol conversion and promotes selectivity towards hydrogen formation. The same effects were observed for catalysts with higher metal loadings. High process temperature and high water-to-ethanol ratio were found to be beneficial for hydrogen production. An extended catalyst stability tests showed no loss of activity over 50 h on reaction stream. The TOC analysis of spent catalysts revealed only insignificant amounts of carbon deposit.
Metal load and oxidative stress driven by organotin compounds on rainbow trout
Authors: Magara Gabriele , Elia Antonia Concetta , Dörr Ambrosius Josef Martin , Abete Maria Cesarina , Brizio Paola , Caldaroni Barbara , Righetti Marzia , Pastorino Paolo , Scoparo Melissa , Prearo Marino
Published: March 2021

Tributyltin-based (TBT) antifouling paints, widely used for the treatment of flooded surfaces, have been banned in 2008 for their high environmental persistence and bioaccumulation in aquatic organisms. Although it is still present in aquatic ecosystems, oxidative stress driven by TBT has been still poorly investigated in fish. The aim of the study was to examine the time-course stress responses in liver of rainbow trout that received a single intraperitoneal injection of tributyltin chloride (TBTC) or tributyltin ethoxide (TBTE), both at a dose of 0.05 and 0.5 mg/kg. Levels of metallothioneins, total glutathione, malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferase were evaluated at 3 and 6 days post-injection. Tin load was measured in the muscle of the same fish. Differences were observed in the time-course accumulation of tin with a clear dose-response relationship. Although individual oxidative stress biomarkers varied, the biomarker profile indicated different stress mechanisms caused by both TBTC and TBTE. The weak induction of metal-trapping metallothioneins and the changes of oxidative stress biomarkers suggested a stress-pressure in both TBT-treated trout, advising for an ecotoxicological risk for freshwater ecosystems.
Developing an Efficient Catalyst Based on Thermal and Acid-Treated Clay for the Removal of Trace Olefins From Aromatic Compounds
Authors: Nouri Nooshin , Tasviri Mahboubeh , Ghasemzadeh Hossein
Published: March 2021

Bentonite is used as a catalyst in the removal of olefins from aromatic compounds and the present study was designed to investigate how its performance might be improved by various treatments. Bentonite from Semnan mine, Iran, was used in the study following initial characterization. In order to investigate the effect of acid and thermal treatments on the removal of olefins from aromatic compounds, bentonite samples were modified using HNO3 at different concentrations (0.15, 0.3, 0.5, 0.7, 1, and 2 M) and were also at temperatures between 100 and 340°C for 3 h. To examine the catalytic activity of bentonite-based catalysts, the samples were evaluated after running batch and continuous experiments. The optimum catalyst was characterized using thermo-programmed desorption (TPD) of NH3 to examine the acidic sites. Scanning Electron Microscopy (SEM) images, nitrogen adsorption-desorption isotherms (BET analysis), and X-ray diffraction (XRD) patterns were used to study the structural changes of the bentonite produced by the acid and thermal activation. The removal of olefins by the catalysts in batch and continuous systems revealed that the sample modified with 0.3 M Nitric acid at 150°C had superior catalytic activity, with olefin conversion remaining at >50% for up to 20 h. Nitrogen adsorption-desorption isotherms showed that acid treatment can produce a mesoporous structure. On the other hand, the TPD analysis indicated that during weak acid treatment, some cations, such as Al3+ and Fe3+, were leached from octahedral sheets and the interlayers of the clay mineral resulting in weak acid sites being generated. Finally, a novel method was proposed and tested for measuring the Bromine Index (BI) using potentiometric titration.
The European Union Global Human Rights Sanctions Regime (EUGHRSR)
Authors: Ruys Tom
Published: March 2021

On December 7, 2020, the Council of the European Union adopted two legal instruments, Council Decision (CFSP) 2020/1999 and Council Regulation (EU) 2020/1998, which together make up the new EU Global Human Rights Sanctions Regime (EUGHRSR). Similar to the U.S. “Global Magnitsky Act,” and in contrast with the EU's existing country-specific sanctions regimes, the EUGHRSR seeks to address human rights abuses worldwide, by providing for the imposition of travel bans as well as financial sanctions on individual human rights offenders—state and non-state alike. The list of designated (natural and legal) persons will be reviewed on a periodic basis.
Tuning in to his-story: an account of radio in Ghana through the experience of B. S. Gadzekpo
Authors: Gadzekpo Audrey
Published: March 2021

This article introduces a personalized account of the early years of radio in Ghana based on an unpublished manuscript by one of its pioneering broadcasters – Bernard Senedzi (B. S.) Gadzekpo. An accomplished writer who produced manuscripts in both English and the Eʋe language, Gadzekpo's radio memoir is written from the vantage point of someone who worked in both the colonial and postcolonial broadcast service for nearly thirty years. It foregrounds African broadcasters in the history of radio and offers insights into the complex realities of Africa's mutable encounter with radio and the strategic role played by local intellectuals in fulfilling its modernization mission during and after the colonial period.
Philippa Foot, l'utilitarisme et la promesse
Authors: Boyer Vincent
Published: March 2021

Dans cet article, nous revenons sur la critique tout à fait originale de l'utilitarisme que Philippa Foot propose dans son œuvre de philosophie morale. Nous montrerons que la confrontation avec cette théorie éthique normative fut l'une des causes qui conduisit la philosophe britannique à reprendre à nouveaux frais la notion de rationalité pratique dans la dernière partie de son œuvre, notamment lors de la discussion qu'elle engage avec l'utilitarisme sur le fondement de l'obligation des promesses dans son livre de 2001,Le Bien naturel.
La disparition des formes aristotéliciennes. À propos d'une démarche clandestine dans les Méditations
Authors: Moyal Georges
Published: March 2021

Même si l'appréhension que l'on peut avoir des formes aristotéliciennes résulte de ce qu'Aristote nomme «induction», rien ne nécessite que leurs composantes soient reliées entre elles de façon intelligible, comme le sont, au contraire, les propriétés de la matière. C'est ce qui porte René Descartes à en débarrasser les sciences par une démarche effectuée subrepticement dans sa VIe Méditation, et à leur substituer la matière, dénominateur commun des êtres naturels. C'est cette démarche — elle continue d’éluder certains de ses lecteurs —, que nous tentons de mettre au jour dans ce qui suit.
La nécessité du mouvement éternel. Note exégétique à Aristote, Physique VIII, 5, 256b8-13
Authors: Gili Luca , Godin-Tremblay Laurence
Published: March 2021

En Physique VIII, 5, 256b8-13, Aristote soutient qu'il est impossible qu'il n'y ait pas de mouvement, parce qu'il a démontré auparavant qu'il est nécessaire qu'il y ait toujours du mouvement. En effet, en Physique VIII, 1, 251b23-28, Aristote avait dit qu'il est nécessaire (necessitate consequentiae) que si le temps est éternel, le mouvement le soit aussi. En Physique VIII, 5, 256b8-13, Aristote introduit en revanche la nécessité du mouvement éternel de sensu diviso. Dans cette note, nous montrons que l'argument de Physique VIII, 1, 251b23-28 implique aussi la nécessité du mouvement éternel de sensu diviso.
Parallel velocity mixing yielding enhanced electron heating during magnetic pumping
Authors: Egedal J. , Schroeder J. , Lichko E.
Published: March 2021

Magnetic wave perturbations are observed in the solar wind and in the vicinity of Earth's bow shock. For such environments, recent work on magnetic pumping with electrons trapped in the magnetic perturbations has demonstrated the possibility of efficient energization of superthermal electrons. Here we also analyse the energization of such energetic electrons for which the transit time through the system is short compared with time scales associated with the magnetic field evolution. In particular, considering an idealized magnetic configuration we show how trapping/detrapping of energetic magnetized electrons can cause effective parallel velocity ($v_{\parallel }$-) diffusion. This parallel diffusion, combined with naturally occurring mechanisms known to cause pitch angle scattering, such as whistler waves, produces enhanced heating rates for magnetic pumping. We find that at low pitch angle scattering rates, the combined mechanism enhances the heating beyond the predictions of the recent theory for magnetic pumping with trapped electrons.
Herbal High: Substance-Induced Psychosis after Consumption of Seeds of the Hawaiian Baby Woodrose
Authors: Sobanski Esther , Dalm Saskia , Sievers Luisa , Külzer Tim , Liesenfeld Heinz , Schmidt-Kittler Halgard , Huss Michael
Published: March 2021

Abstract. Seeds of the Hawaiian Baby Woodrose (HBWR, Argyreia nervosa) are known as “legal or herbal highs” and can be easily purchased online in Germany. They contain various ergot alkaloids, including lysergic acid amide (LSA), which is chemically related to lysergic acid diethylamide (LSD). Pharmacological data are limited but suggest that LSA-concentration in HBWR seeds is highly variable, and that adverse psychiatric and somatic effects are not related to LSA-dosage. Anecdotal, mostly cross-sectional clinical case reports describe spontaneous remission of intoxication-related somatic and psychiatric symptoms as well as intoxication-related death. Treatment recommendations for LSA-induced psychiatric syndromes are not available. We report here on the clinical course and treatment of a drug-induced psychosis after consumption of HBWR seeds. The adolescent had consumed HBWR seeds once before without suffering any negative effects.
Aberrant Gcm1 expression mediates Wnt/β-catenin pathway activation in folate deficiency involved in neural tube defects
Authors: Li Jianting , Xie Qiu , Gao Jun , Wang Fang , Bao Yihua , Wu Lihua , Yang Lihong , Liu Zhizhen , Guo Rui , Khan Ajab , Dan Liu  , Li Caihua , Wu Jianxin , Xie Jun
Published: March 2021

Wnt signaling plays a major role in early neural development. An aberrant activation in Wnt/β-catenin pathway causes defective anteroposterior patterning, which results in neural tube closure defects (NTDs). Changes in folate metabolism may participate in early embryo fate determination. We have identified that folate deficiency activated Wnt/β-catenin pathway by upregulating a chorion-specific transcription factor Gcm1. Specifically, folate deficiency promoted formation of the Gcm1/β-catenin/T-cell factor (TCF4) complex formation to regulate the Wnt targeted gene transactivation through Wnt-responsive elements. Moreover, the transcription factor Nanog upregulated Gcm1 transcription in mESCs under folate deficiency. Lastly, in NTDs mouse models and low-folate NTDs human brain samples, Gcm1 and Wnt/β-catenin targeted genes related to neural tube closure are specifically overexpressed. These results indicated that low-folate level promoted Wnt/β-catenin signaling via activating Gcm1, and thus leaded into aberrant vertebrate neural development.
Ubiquitin-specific protease 53 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells
Authors: Baek Dawoon , Park Kwang Hwan , Lee Kyoung-Mi , Jung Sujin , Joung Soyeong , Kim Jihyun , Lee Jin Woo
Published: March 2021

The ubiquitin protease pathway plays important role in human bone marrow-derived mesenchymal stem cell (hBMSC) differentiation, including osteogenesis. However, the function of deubiquitinating enzymes in osteogenic differentiation of hBMSCs remains poorly understood. In this study, we aimed to investigate the role of ubiquitin-specific protease 53 (USP53) in the osteogenic differentiation of hBMSCs. Based on re-analysis of the Gene Expression Omnibus database, USP53 was selected as a positive regulator of osteogenic differentiation in hBMSCs. Overexpression of USP53 by lentivirus enhanced osteogenesis in hBMSCs, whereas knockdown of USP53 by lentivirus inhibited osteogenesis in hBMSCs. In addition, USP53 overexpression increased the level of active β-catenin and enhanced the osteogenic differentiation of hBMSCs. This effect was reversed by the Wnt/β-catenin inhibitor DKK1. Mass spectrometry showed that USP53 interacted with F-box only protein 31 (FBXO31) to promote proteasomal degradation of β-catenin. Inhibition of the osteogenic differentiation of hBMSCs by FBXO31 was partially rescued by USP53 overexpression. Animal studies showed that hBMSCs with USP53 overexpression significantly promoted bone regeneration in mice with calvarial defects. These results suggested that USP53 may be a target for gene therapy for bone regeneration.
Operando high-pressure investigation of size-controlled CuZn catalysts for the methanol synthesis reaction
Authors: Divins Núria J. , Kordus David , Timoshenko Janis , Sinev Ilya , Zegkinoglou Ioannis , Bergmann Arno , Chee See Wee , Widrinna Simon , Karslıoğlu Osman , Mistry Hemma , Lopez Luna Mauricio , Zhong Jian Qiang , Hoffman Adam S. , Boubnov Alexey , Boscoboinik J. Anibal , Heggen Marc , Dunin-Borkowski Rafal E. , Bare Simon R. , Cuenya Beatriz Roldan
Published: March 2021

Although Cu/ZnO-based catalysts have been long used for the hydrogenation of CO2 to methanol, open questions still remain regarding the role and the dynamic nature of the active sites formed at the metal-oxide interface. Here, we apply high-pressure operando spectroscopy methods to well-defined Cu and Cu0.7Zn0.3 nanoparticles supported on ZnO/Al2O3, γ-Al2O3 and SiO2 to correlate their structure, composition and catalytic performance. We obtain similar activity and methanol selectivity for Cu/ZnO/Al2O3 and CuZn/SiO2, but the methanol yield decreases with time on stream for the latter sample. Operando X-ray absorption spectroscopy data reveal the formation of reduced Zn species coexisting with ZnO on CuZn/SiO2. Near-ambient pressure X-ray photoelectron spectroscopy shows Zn surface segregation and the formation of a ZnO-rich shell on CuZn/SiO2. In this work we demonstrate the beneficial effect of Zn, even in diluted form, and highlight the influence of the oxide support and the Cu-Zn interface in the reactivity.
Epidermal growth factor receptor signaling uncouples germ cells from the somatic follicular compartment at ovulation
Authors: Abbassi Laleh , El-Hayek Stephany , Carvalho Karen Freire , Wang Wusu , Yang Qin , Granados-Aparici Sofia , Mondadori Rafael , Bordignon Vilceu , Clarke Hugh J.
Published: March 2021

Germ cells are physically coupled to somatic support cells of the gonad during differentiation, but this coupling must be disrupted when they are mature, freeing them to participate in fertilization. In mammalian females, coupling occurs via specialized filopodia that project from the ovarian follicular granulosa cells to the oocyte. Here, we show that signaling through the epidermal growth factor receptor (EGFR) in the granulosa, which becomes activated at ovulation, uncouples the germ and somatic cells by triggering a massive and temporally synchronized retraction of the filopodia. Although EGFR signaling triggers meiotic maturation of the oocyte, filopodial retraction is independent of the germ cell state, being regulated solely within the somatic compartment, where it requires ERK-dependent calpain-mediated loss of filopodia-oocyte adhesion followed by Arp2/3-mediated filopodial shortening. By uncovering the mechanism regulating germ-soma uncoupling at ovulation, our results open a path to improving oocyte quality in human and animal reproduction.
Isolated copper–tin atomic interfaces tuning electrocatalytic CO2 conversion
Authors: Ren Wenhao , Tan Xin , Qu Jiangtao , Li Sesi , Li Jiantao , Liu Xin , Ringer Simon P. , Cairney Julie M. , Wang Kaixue , Smith Sean C. , Zhao Chuan
Published: March 2021

Direct experimental observations of the interface structure can provide vital insights into heterogeneous catalysis. Examples of interface design based on single atom and surface science are, however, extremely rare. Here, we report Cu–Sn single-atom surface alloys, where isolated Sn sites with high surface densities (up to 8%) are anchored on the Cu host, for efficient electrocatalytic CO2 reduction. The unique geometric and electronic structure of the Cu–Sn surface alloys (Cu97Sn3 and Cu99Sn1) enables distinct catalytic selectivity from pure Cu100 and Cu70Sn30 bulk alloy. The Cu97Sn3 catalyst achieves a CO Faradaic efficiency of 98% at a tiny overpotential of 30 mV in an alkaline flow cell, where a high CO current density of 100 mA cm−2 is obtained at an overpotential of 340 mV. Density functional theory simulation reveals that it is not only the elemental composition that dictates the electrocatalytic reactivity of Cu–Sn alloys; the local coordination environment of atomically dispersed, isolated Cu–Sn bonding plays the most critical role.
Author Correction: Faster chiral versus collinear magnetic order recovery after optical excitation revealed by femtosecond XUV scattering
Authors: Kerber Nico , Ksenzov Dmitriy , Freimuth Frank , Capotondi Flavio , Pedersoli Emanuele , Lopez-Quintas Ignacio , Seng Boris , Cramer Joel , Litzius Kai , Lacour Daniel , Zabel Hartmut , Mokrousov Yuriy , Kläui Mathias , Gutt Christian
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21915-9
Author Correction: All-optical switching of an epsilon-near-zero plasmon resonance in indium tin oxide
Authors: Bohn Justus , Luk Ting Shan , Tollerton Craig , Hutchings Sam W. , Brener Igal , Horsley Simon , Barnes William L. , Hendry Euan
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22020-7
Novel combination of CRISPR-based gene drives eliminates resistance and localises spread
Authors: Faber Nicky R. , McFarlane Gus R. , Gaynor R. Chris , Pocrnic Ivan , Whitelaw C. Bruce A. , Gorjanc Gregor
Published: March 2021

Invasive species are among the major driving forces behind biodiversity loss. Gene drive technology may offer a humane, efficient and cost-effective method of control. For safe and effective deployment it is vital that a gene drive is both self-limiting and can overcome evolutionary resistance. We present HD-ClvR in this modelling study, a novel combination of CRISPR-based gene drives that eliminates resistance and localises spread. As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and economic losses. HD-ClvR combats resistance allele formation by combining a homing gene drive with a cleave-and-rescue gene drive. The inclusion of a self-limiting daisyfield gene drive allows for controllable localisation based on animal supplementation. We use both randomly mating and spatial models to simulate this strategy. Our findings show that HD-ClvR could effectively control a targeted grey squirrel population, with little risk to other populations. HD-ClvR offers an efficient, self-limiting and controllable gene drive for managing invasive pests.
Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection
Authors: Masterson Claire H. , Tabuchi Arata , Hogan Grace , Fitzpatrick Glenn , Kerrigan Steven W. , Jerkic Mirjana , Kuebler Wolfgang M. , Laffey John G. , Curley Gerard F.
Published: March 2021

Mesenchymal stem/stromal cells (MSCs) have demonstrated efficacy in pre-clinical models of inflammation and tissue injury, including in models of lung injury and infection. Rolling, adhesion and transmigration of MSCs appears to play a role during MSC kinetics in the systemic vasculature. However, a large proportion of MSCs become entrapped within the lungs after intravenous administration, while the initial kinetics and the site of arrest of MSCs in the pulmonary vasculature are unknown. We examined the kinetics of intravascularly administered MSCs in the pulmonary vasculature using a microfluidic system in vitro and intra-vital microscopy of intact mouse lung. In vitro,MSCs bound to endothelium under static conditions but not under laminar flow. VCAM-1 antibodies did not affect MSC binding.Intravitalmicroscopy demonstrated MSC arrest at pulmonary micro-vessel bifurcations due to size obstruction. Retention of MSCs in the pulmonary microvasculature was increased inEscherichia coli-infected animals. Trapped MSCs deformed over time and appeared to release microvesicles. Labelled MSCs retained therapeutic efficacy against pneumonia. Our results suggest that MSCs are physically obstructed in pulmonary vasculature and do not display properties of rolling/adhesion, while retention of MSCs in the infected lung may require receptor interaction.
Evaluation of the German biographic screening interview for fetal alcohol spectrum disorder (BSI-FASD)
Authors: Widder Michael , Mierzwa Luisa , Schwerg Lina , Schecke Henrike , Kornhuber Johannes , Bouna-Pyrrou Polyxeni , Bumb Jan Malte , Richter-Schmidinger Tanja , Lenz Bernd
Published: March 2021

Alcohol consumption during pregnancy may lead to permanent damage in the offspring, including fetal alcohol spectrum disorders (FASD), which have an estimated prevalence of 1–8% worldwide. In adulthood, diagnosing FASD is time-consuming and costly. This study aimed to evaluate the discriminatory power of a German screening instrument for FASD in adults—the biographic screening interview (BSI-FASD). In an open-label comparative cohort study wherein a one-time survey was administered per participant, we compared 22 subjects with confirmed FASD with control groups of 15 subjects diagnosed with attention deficit hyperactivity disorder (ADHD), 20 subjects with alcohol or opiate dependence, 18 subjects with depression, and 31 controls without prenatal alcohol exposure. The BSI-FASD was found to be resource-efficient, user-friendly, comprehensible, and easily applicable. It provided an overall good convergent and discriminant validity with a sensitivity of 0.77 (adapted 0.86) and specificities between 0.70 and 1.00. The BSI-FASD subdomains differed in their power to differentiate FASD from the groups. This study established that the BSI-FASD is an efficient instrument to screen adults with suspected FASD. The BSI-FASD may facilitate future diagnostic evaluation and thereby contribute to improved treatment of affected individuals.
High-resolution shock-capturing numerical simulations of three-phase immiscible fluids from the unsaturated to the saturated zone
Authors: Feo Alessandra , Celico Fulvio
Published: March 2021

Numerical modeling of immiscible contaminant fluid flow in unsaturated and saturated porous aquifers is of great importance in many scientific fields to properly manage groundwater resources. We present a high-resolution numerical model that simulates three-phase immiscible fluid flow in both unsaturated and saturated zone in a porous aquifer. We use coupled conserved mass equations for each phase and study the dynamics of a multiphase fluid flow as a function of saturation, capillary pressure, permeability, and porosity of the different phases, initial and boundary conditions. To deal with the sharp front originated from the partial differential equations’ nonlinearity and accurately propagate the sharp front of the fluid component, we use a high-resolution shock-capturing method to treat discontinuities due to capillary pressure and permeabilities that depend on the saturation of the three different phases. The main approach to the problem’s numerical solution is based on (full) explicit evolution of the discretized (in-space) variables. Since explicit methods require the time step to be sufficiently small, this condition is very restrictive, particularly for long-time integrations. With the increased computational speed and capacity of today’s multicore computer, it is possible to simulate in detail contaminants’ fate flow using high-performance computing.
On topological properties of COVID-19: predicting and assessing pandemic risk with network statistics
Authors: So Mike K. P. , Chu Amanda M. Y. , Tiwari Agnes , Chan Jacky N. L.
Published: March 2021

The spread of coronavirus disease 2019 (COVID-19) has caused more than 80 million confirmed infected cases and more than 1.8 million people died as of 31 December 2020. While it is essential to quantify risk and characterize transmission dynamics in closed populations using Susceptible-Infection-Recovered modeling, the investigation of the effect from worldwide pandemic cannot be neglected. This study proposes a network analysis to assess global pandemic risk by linking 164 countries in pandemic networks, where links between countries were specified by the level of ‘co-movement’ of newly confirmed COVID-19 cases. More countries showing increase in the COVID-19 cases simultaneously will signal the pandemic prevalent over the world. The network density, clustering coefficients, and assortativity in the pandemic networks provide early warning signals of the pandemic in late February 2020. We propose a preparedness pandemic risk score for prediction and a severity risk score for pandemic control. The preparedness risk score contributed by countries in Asia is between 25% and 50% most of the time after February and America contributes around 40% in July 2020. The high preparedness risk contribution implies the importance of travel restrictions between those countries. The severity risk score of America and Europe contribute around 90% in December 2020, signifying that the control of COVID-19 is still worrying in America and Europe. We can keep track of the pandemic situation in each country using an online dashboard to update the pandemic risk scores and contributions.
A descriptive analysis of antimicrobial resistance patterns of WHO priority pathogens isolated in children from a tertiary care hospital in India
Authors: Mogasale Vijayalaxmi V. , Saldanha Prakash , Pai Vidya , Rekha P. D. , Mogasale Vittal
Published: March 2021

The World Health Organization (WHO) has articulated a priority pathogens list (PPL) to provide strategic direction to research and develop new antimicrobials. Antimicrobial resistance (AMR) patterns of WHO PPL in a tertiary health care facility in Southern India were explored to understand the local priority pathogens. Culture reports of laboratory specimens collected between 1st January 2014 and 31st October 2019 from paediatric patients were extracted. The antimicrobial susceptibility patterns for selected antimicrobials on the WHO PPL were analysed and reported. Of 12,256 culture specimens screened, 2335 (19%) showed culture positivity, of which 1556 (66.6%) were organisms from the WHO-PPL. E. coli was the most common organism isolated (37%), followed by Staphylococcus aureus (16%). Total of 72% of E. coli were extended-spectrum beta-lactamases (ESBL) producers, 55% of Enterobacteriaceae were resistant to 3rd generation cephalosporins due to ESBL, and 53% of Staph. aureus were Methicillin-resistant. The analysis showed AMR trends and prevalence patterns in the study setting and the WHO-PPL document are not fully comparable. This kind of local priority difference needs to be recognised in local policies and practices.
Differences in clinical severity of respiratory viral infections in hospitalized children
Authors: Althouse Benjamin M. , Flasche Stefan , Toizumi Michiko , Nguyen Hien-Anh Thi , Vo Hien Minh , Le Minh Nhat , Hashizume Masahiro , Ariyoshi Koya , Anh Dang Duc , Rodgers Gail L. , Klugman Keith P. , Hu Hao , Yoshida Lay-Myint
Published: March 2021

It is uncertain whether clinical severity of an infection varies by pathogen or by multiple infections. Using hospital-based surveillance in children, we investigate the range of clinical severity for patients singly, multiply, and not infected with a group of commonly circulating viruses in Nha Trang, Vietnam. RT-PCR was performed to detect 13 respiratory viruses in nasopharyngeal samples from enrolled patients. We apply a novel clinical severity score and examine associations with the odds of being severe and differences in raw severity scores. We find no difference in severity between 0-, 1-, and 2-concurrent infections and little differences in severity between specific viruses. We find RSV and HMPV infections to be associated with 2- and 1.5-fold increase in odds of being severe, respectively, and that infection with ADV is consistently associated with lower risk of severity. Clinically, based on the results here, if RSV or HMPV virus is suspected, PCR testing for confirmatory diagnosis and for detection of multiple coinfecting viruses would be fruitful to assess whether a patient’s disease course is going to be severe.
Transcriptional profiling of two contrasting genotypes uncovers molecular mechanisms underlying salt tolerance in alfalfa
Authors: Kaundal Rakesh , Duhan Naveen , Acharya Biswa R. , Pudussery Manju V. , Ferreira Jorge F. S. , Suarez Donald L. , Sandhu Devinder
Published: March 2021

Alfalfa is an important forage crop that is moderately tolerant to salinity; however, little is known about its salt-tolerance mechanisms. We studied root and leaf transcriptomes of a salt-tolerant (G03) and a salt-sensitive (G09) genotype, irrigated with waters of low and high salinities. RNA sequencing led to 1.73 billion high-quality reads that were assembled into 418,480 unigenes; 35% of which were assigned to 57 Gene Ontology annotations. The unigenes were assigned to pathway databases for understanding high-level functions. The comparison of two genotypes suggested that the low salt tolerance index for transpiration rate and stomatal conductance of G03 compared to G09 may be due to its reduced salt uptake under salinity. The differences in shoot biomass between the salt-tolerant and salt-sensitive lines were explained by their differential expressions of genes regulating shoot number. Differentially expressed genes involved in hormone-, calcium-, and redox-signaling, showed treatment- and genotype-specific differences and led to the identification of various candidate genes involved in salinity stress, which can be investigated further to improve salinity tolerance in alfalfa. Validation of RNA-seq results using qRT-PCR displayed a high level of consistency between the two experiments. This study provides valuable insight into the molecular mechanisms regulating salt tolerance in alfalfa.
Longitudinal optical coherence tomography to visualize the in vivo response of middle ear biofilms to antibiotic therapy
Authors: Won Jungeun , Hong Wenzhou , Khampang Pawjai , Spillman Darold R. , Marshall Samuels , Yan Ke , Porter Ryan G. , Novak Michael A. , Kerschner Joseph E. , Boppart Stephen A.
Published: March 2021

Studying the impact of antibiotic treatment on otitis media (OM), the leading cause of primary care office visits during childhood, is critical to develop appropriate treatment strategies. Tracking dynamic middle ear conditions during antibiotic treatment is not readily applicable in patients, due to the limited diagnostic techniques available to detect the smaller amount and variation of middle ear effusion (MEE) and middle ear bacterial biofilm, responsible for chronic and recurrent OM. To overcome these challenges, a handheld optical coherence tomography (OCT) system has been developed to monitor in vivo response of biofilms and MEEs in the OM-induced chinchilla model, the standard model for human OM. As a result, the formation of MEE as well as biofilm adherent to the tympanic membrane (TM) was longitudinally assessed as OM developed. Various types of MEEs and biofilms in the chinchilla model were identified, which showed comparable features as those in humans. Furthermore, the effect of antibiotics on the biofilm as well as the amount and type of MEEs was investigated with low-dose and high-dose treatment (ceftriaxone). The capability of OCT to non-invasively track and examine middle ear conditions is highly beneficial for therapeutic OM studies and will lead to improved management of OM in patients.
Localized surface plasmon resonance in deep ultraviolet region below 200 nm using a nanohemisphere on mirror structure
Authors: Shimanoe Kohei , Endo Soshi , Matsuyama Tetsuya , Wada Kenji , Okamoto Koichi
Published: March 2021

Localized surface plasmon resonance (LSPR) was performed in the deep ultraviolet (UVC) region with Al nanohemisphere structures fabricated by means of a simple method using a combination of vapor deposition, sputtering, and thermal annealing without top-down nanofabrication technology such as electron beam lithography. The LSPR in the UV region was obtained and tuned by the initial metal film thickness, annealing temperature, and dielectric spacer layer thickness. Moreover, we achieved a flexible tuning of the LSPR in a much deeper UVC region below 200 nm using a nanohemisphere on a mirror (NHoM) structure. NHoM is a structure in which a metal nanohemisphere is formed on a metal substrate that is interposed with an Al2O3 thin film layer. In the experimental validation, Al and Ga were used for the metal hemispheres. The LSPR spectrum of the NHoM structures was split into two peaks, and the peak intensities were enhanced and sharpened. The shorter branch of the LSPR peak appeared in the UVC region below 200 nm. Both the peak intensities and linewidth were flexibly tuned by the spacer thickness. This structure can contribute to new developments in the field of deep UV plasmonics.
Association between patient-reported functional measures and incident falls
Authors: Yip Wanfen , Ge Lixia , Heng Bee Hoon , Tan Woan Shin
Published: March 2021

Lower extremity muscle strength, and functional limitations are important modifiable predictors of falls, but are often examined using performance based measures. We examined the association between self-reported physical function limitations, determined using Late-Life Function and Disability Instrument(LLFDI) and incident falls in community-dwelling elderly individuals. 283 older adults participants were included in this analysis. Physical function limitations were defined as a person’s difficulty in completing items of the lower extremity function domain and composite scores of the LLFDI. Information on falls was obtained through a standardised questionnaire. At one-year follow-up, 15.2% (43) of the participants experienced their first fall. In the multivariable analysis, individuals who reported difficulties in items of lower extremity function domain were more likely to experience a fall (incidence rate ratio[IRR]: ranging between 2.43 and 7.01; all P ≤ 0.046). In addition, decreasing advanced lower extremity function scores (IRR: 1.70, 95% confidence interval[CI]): 1.04, 2.78) and overall function component score (IRR: 2.05, 95% CI: 1.22, 3.44) were associated with higher risk of incident falls. Physical function limitations, determined using LLFDI, were associated with incident falls. Our findings provide further evidence that the LLFDI function component has the potential to be used as a self-assessment tool for fall risk.
Heterozygous APC germline mutations impart predisposition to colorectal cancer
Authors: Preisler Livia , Habib Aline , Shapira Guy , Kuznitsov-Yanovsky Liron , Mayshar Yoav , Carmel-Gross Ilana , Malcov Mira , Azem Foad , Shomron Noam , Kariv Revital , Hershkovitz Dov , Ben-Yosef Dalit
Published: March 2021

Familial adenomatous polyposis (FAP) is an inherited syndrome caused by a heterozygous adenomatous polyposis coli (APC) germline mutation, associated with a profound lifetime risk for colorectal cancer. While it is well accepted that tumorigenic transformation is initiated following acquisition of a second mutation and loss of function of the APC gene, the role of heterozygous APC mutation in this process is yet to be discovered. This work aimed to explore whether a heterozygous APC mutation induces molecular defects underlying tumorigenic transformation and how different APC germline mutations predict disease severity. Three FAP-human embryonic stem cell lines (FAP1/2/3-hESC lines) carrying germline mutations at different locations of the APC gene, and two control hESC lines free of the APC mutation, were differentiated into colon organoids and analyzed by immunohistochemistry and RNA sequencing. In addition, data regarding the genotype and clinical phenotype of the embryo donor parents were collected from medical records. FAP-hESCs carrying a complete loss-of-function of a single APC allele (FAP3) generated complex and molecularly mature colon organoids, which were similar to controls. In contrast, FAP-hESCs carrying APC truncation mutations (FAP1 and FAP2) generated only few cyst-like structures and cell aggregates of various shape, occasionally with luminal parts, which aligned with their failure to upregulate critical differentiation genes early in the process, as shown by RNA sequencing. Abnormal disease phenotype was shown also in non-pathological colon of FAP patients by the randomly distribution of proliferating cells throughout the crypts, compared to their focused localization in the lower part of the crypt in healthy/non-FAP patients. Genotype/phenotype analysis revealed correlations between the colon organoid maturation potential and FAP severity in the carrier parents. In conclusion, this study suggest that a single truncated APC allele is sufficient to initiate early molecular tumorigenic activity. In addition, the results hint that patient-specific hESC-derived colon organoids can probably predict disease severity among FAP patients.
The impact of movement sonification on haptic perception changes with aging
Authors: Landelle C. , Danna J. , Nazarian B. , Amberg M. , Giraud F. , Pruvost L. , Kronland-Martinet R. , Ystad S. , Aramaki M. , Kavounoudias Anne
Published: March 2021

Combining multisensory sources is crucial to interact with our environment, especially for older people who are facing sensory declines. Here, we examined the influence of textured sounds on haptic exploration of artificial textures in healthy younger and older adults by combining a tactile device (ultrasonic display) with synthetized textured sounds. Participants had to discriminate simulated textures with their right index while they were distracted by three disturbing, more or less textured sounds. These sounds were presented as a real-time auditory feedback based on finger movement sonification and thus gave the sensation that the sounds were produced by the haptic exploration. Finger movement velocity increased across both groups in presence of textured sounds (Rubbing or Squeaking) compared to a non-textured (Neutral) sound. While young adults had the same discrimination threshold, regardless of the sound added, the older adults were more disturbed by the presence of the textured sounds with respect to the Neutral sound. Overall, these findings suggest that irrelevant auditory information was taken into account by all participants, but was appropriately segregated from tactile information by young adults. Older adults failed to segregate auditory information, supporting the hypothesis of general facilitation of multisensory integration with aging.