bluuebunny/crossref_metadata_2025 huggingface dataset:
Timing for Introduction of Total Laparoscopic Living Donor Right Hepatectomy; Initial Experience Based on the Data of Laparoscopic Major Hepatectomy
Authors: Lee Boram , Choi YoungRok , Lee Woohyung , Park Youngmi , Kim Kil Hwan , Hyun In Gun , Han Sun Jong , Cho Jai Young , Yoon Yoo-Seok , Han Ho-Seong
Published: June 2020

Background.

This study evaluated the timing of safe introduction of total laparoscopic donor right hepatectomy (TLDRH) based on outcomes of laparoscopic major hepatectomy (LMH).

Methods.

The data of 1013 consecutive patients who underwent laparoscopic liver resection from 2003 to 2017 were reviewed; the cumulative sum method was used to evaluate the learning curve of LMH. Patients were divided into 3 groups according to the timing of introduction of TLDRH (since 2010) and learning curve of LMH. Surgical outcomes of LMH and TLDRH were evaluated.

Results.

Cumulative sum analysis demonstrated a learning curve of approximately 73 cases of LMH. In phase I (before the introduction of TLDRH, 2003–2009), 38 cases of LMH were performed. Phase II (after the introduction of TLDRH until learning curve of LMH, 2010–2014), 35 and 15 cases of LMH and TLDRH were performed, respectively. Phase III (after learning curve of LMH until 2017, 2014–2017), 59 and 20 cases of LMH and TLDRH were performed, respectively. In cases of LMH, there was significant improvement in the operation time 398.9 ± 140.9 versus 403.7 ± 165.2 versus 265.5 ± 91.7; P < 0.001), estimated blood loss (1122.9 ± 1460.2 versus 1209.3 ± 1409.1 versus 359.8 ± 268.8; P < 0.001), and open conversion rate (26.3% versus 22.9% versus 13.6%; P = 0.026) between phases I versus II versus III. In cases of TLDRH, the operation time (567.8 ± 117.9 versus 344.2 ± 71.8; P < 0.001), estimated blood loss (800.7 ± 514.8 versus 439.4 ± 347.0; P = 0.004), and hospital stay (12.5 ± 4.36 versus 9.15 ± 4.84; P = 0.025) significantly improved in phase III.

Conclusions.

Overcoming the learning curve of LMH before starting TLDRH is advisable to ensure donor’s surgical outcomes.
Comparison of Amyloid in Cerebrospinal Fluid, Brain Imaging, and Autopsy in a Case of Progressive Supranuclear Palsy
Authors: Kim Kyung Hye , Seo Jae Deuk , Kim Eun Soo , Kim Hyang-Sook , Jeon Sumin , Pak Kyoungjune , Lee Myung Jun , Lee Jae-Hyeok , Lee Young Min , Lee Kangyoon , Shin Jin-Hong , Ko Jun Kyeung , Jung Na-Yeon , Lee Jae Meen , Yoon Jin A. , Hwang Chungsu , Ahn Jae-Woo , Sung Suk , Spina Salvatore , Seeley William W. , Choi Kyung-Un , Huh Gi Yeong , Kim Eun-Joo
Published: June 2020

Cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aβ1-42) and amyloid positron emission tomography (PET) are the 2 main Alzheimer disease amyloid biomarkers that have been validated in neuropathologically confirmed Alzheimer disease cases. Although many studies have shown concordance of amyloid positivity or negativity between CSF Aβ1-42 and amyloid PET, several studies also reported discrepancies between these 2 Aβ biomarkers. We conducted a comparison of CSF Aβ1-42 level, amyloid PET, and autopsy findings in a case with progressive supranuclear palsy in which biomarker acquisition and postmortem pathologic examination were conducted almost at the same time. Our case with antemortem CSF Aβ1-42 (+)/amyloid PET (−) who was pathologically confirmed with Aβ pathology in the cerebral cortex may indicate CSF Aβ1-42 is more sensitive for assessing in vivo Aβ than amyloid PET.
Stokes at 200: a celebration of the remarkable achievements of Sir George Gabriel Stokes two hundred years after his birth
Authors: Cardoso Silvana S. S. , Cartwright Julyan H. E. , Huppert Herbert E. , Ness Christopher
Published: June 2020

Sir George Gabriel Stokes PRS was for 30 years an inimitable Secretary of the Royal Society and its President from 1885 to 1890. Two hundred years after his birth, Stokes is a towering figure in physics and applied mathematics; fluids, asymptotics, optics, acoustics among many other fields. At the Stokes
200
meeting, held at Pembroke College, Cambridge from 15–18th September 2019, an invited audience of about 100 discussed the state of the art in all the modern research fields that have sprung from his work in physics and mathematics, along with the history of how we have got from Stokes’ contributions to where we are now. This theme issue is based on work presented at the Stokes
200
meeting. In bringing together people whose work today is based upon Stokes’ own, we aim to emphasize his influence and legacy at 200 to the community as a whole.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Stokes' mathematical education
Authors: Barrow-Green June
Published: June 2020

George Gabriel Stokes won the coveted title of Senior Wrangler in 1841, a year in which the examination papers for the Cambridge Mathematical Tripos were notoriously difficult. Coming top in the Mathematical Tripos was a notable achievement, but for Stokes it was a prize hard won after several years of preparation, and not only years spent at Cambridge. When Stokes arrived at Pembroke College, he had spent the previous two years at Bristol College, a school which prided itself on its success in preparing students for Oxford and Cambridge. This article follows Stokes' path to the senior wranglership, tracing his mathematical journey from his arrival in Bristol to the end of his final year of undergraduate study at Cambridge.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Shallow free-surface Stokes flow around a corner
Authors: Hinton Edward M. , Hogg Andrew J. , Huppert Herbert E.
Published: June 2020

The steady lateral spreading of a free-surface viscous flow down an inclined plane around a vertex from which the channel width increases linearly with downstream distance is investigated analytically, numerically and experimentally. From the vertex the channel wall opens by an angle
α
to the downslope direction and the viscous fluid spreads laterally along it before detaching. The motion is modelled using lubrication theory and the distance at which the flow detaches is computed as a function of
α
using analytical and numerical methods. Far downslope after detachment, it is shown that the motion is accurately modelled in terms of a similarity solution. Moreover, the detachment point is well approximated by a simple expression for a broad range of opening angles. The results are corroborated through a series of laboratory experiments and the implication for the design of barriers to divert lava flows are discussed.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Use of Stokes’ theorem for plasma confinement
Authors: MacKay R. S.
Published: June 2020

Stokes’ theorem, in its original form and Cartan’s generalization, is crucial for designing magnetic fields to confine plasma (ionized gas). The paper illustrates its use, in particular to address the question whether quasi-symmetric fields, those for which guiding-centre motion is integrable, can be made with little or no toroidal current.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
The Navier–Stokes regularity problem
Authors: Robinson James C.
Published: June 2020

There is currently no proof guaranteeing that, given a smooth initial condition, the three-dimensional Navier–Stokes equations have a unique solution that exists for all positive times. This paper reviews the key rigorous results concerning the existence and uniqueness of solutions for this model. In particular, the link between the regularity of solutions and their uniqueness is highlighted.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Viscous flow and collapse of macroscopic cavities in a granular material in terms of a Darcylet
Authors: Sano Osamu
Published: June 2020

Viscous flow through a granular material that has a macroscopic cavity is obtained on the basis of the Stokes and the generalized Darcy’s equation. A new singularity termed ‘Darcylet’, a fundamental flow in the granular material that acts like a point force with negative direction, is proposed, which is applied to elucidate the interaction of two cavities. Depending on the configuration of the latter, the volume flux into the cavity increases, which enhances the local stresses on the boundary, causes the collapse of cavities and triggers landslides.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Evaporation-induced Rayleigh–Taylor instabilities in polymer solutions
Authors: Mossige E. J. , Chandran Suja V. , Islamov M. , Wheeler S. F. , Fuller Gerald. G.
Published: June 2020

Understanding the mechanics of detrimental convective instabilities in drying polymer solutions is crucial in many applications such as the production of film coatings. It is well known that solvent evaporation in polymer solutions can lead to Rayleigh-Bénard or Marangoni-type instabilities. Here, we reveal another mechanism, namely that evaporation can cause the interface to display Rayleigh–Taylor instabilities due to the build-up of a dense layer at the air–liquid interface. We study experimentally the onset time (
t

p

) of the instability as a function of the macroscopic properties of aqueous polymer solutions, which we tune by varying the polymer concentration (
c
0
), molecular weight and polymer type. In dilute solutions,
t

p

shows two limiting behaviours depending on the polymer diffusivity. For high diffusivity polymers (low molecular weight), the pluming time scales as

c
0

−
2

/

3

. This result agrees with previous studies on gravitational instabilities in miscible systems where diffusion stabilizes the system. On the other hand, in low diffusivity polymers the pluming time scales as

c
0

−
1

. The stabilizing effect of an effective interfacial tension, similar to those in immiscible systems, explains this strong concentration dependence. Above a critical concentration,

c
^

, viscosity delays the growth of the instability, allowing time for diffusion to act as the dominant stabilizing mechanism. This results in
t

p

scaling as (
ν
/
c
0
)
2/3
.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Nonlinear dynamics determines the thermodynamic instability of condensed matter
in vacuo
Authors: Cartwright Julyan H. E.
Published: June 2020

Condensed matter is thermodynamically unstable in a vacuum. That is what thermodynamics tells us through the relation showing that condensed matter at temperatures above absolute zero always has non-zero vapour pressure. This instability implies that at low temperatures energy must not be distributed equally among atoms in the crystal lattice but must be concentrated. In dynamical systems such concentrations of energy in localized excitations are well known in the form of discrete breathers, solitons and related nonlinear phenomena. It follows that to satisfy thermodynamics such localized excitations must exist in systems of condensed matter at arbitrarily low temperature and as such the nonlinear dynamics of condensed matter is crucial for its thermodynamics.

This article is part of the theme issue ‘Stokes at 200 (Part 1)’.
Minimal transmission in an influenza A (H3N2) human challenge-transmission model within a controlled exposure environment
Authors: Nguyen-Van-Tam Jonathan S. , Killingley Ben , Enstone Joanne , Hewitt Michael , Pantelic Jovan , Grantham Michael L. , de Mesquita P. Jacob Bueno , Lambkin-Williams Robert , Gilbert Anthony , Mann Alexander , Forni John , Noakes Catherine J. , Levine Min Z. , Berman LaShondra , Lindstrom Stephen , Cauchemez Simon , Bischoff Werner , Tellier Raymond , Milton Donald K. ,   for the EMIT Consortium.
Published: June 2020

Uncertainty about the importance of influenza transmission by airborne droplet nuclei generates controversy for infection control. Human challenge-transmission studies have been supported as the most promising approach to fill this knowledge gap. Healthy, seronegative volunteer ‘Donors’ (n=52) were randomly selected for intranasal challenge with influenza A/Wisconsin/67/2005 (H3N2). ‘Recipients’ randomized to Intervention (IR, n=40) or Control (CR, n=35) groups were exposed to Donors for four days. IRs wore face shields and hand sanitized frequently to limit large droplet and contact transmission. One transmitted infection was confirmed by serology in a CR, yielding a secondary attack rate of 2.9% among CR, 0% in IR (p=0.47 for group difference), and 1.3% overall, significantly less than 16% (p<0.001) expected based on a proof-of-concept study secondary attack rate and considering that there were twice as many Donors and days of exposure. The main difference between these studies was mechanical building ventilation in the follow-on study, suggesting a possible role for aerosols.

Author summary

Understanding the relative importance of influenza modes of transmission informs strategic use of preventive measures to reduce influenza risk in high-risk settings such as hospitals and is important for pandemic preparedness. Given the increasing evidence from epidemiological modelling, exhaled viral aerosol, and aerobiological survival studies supporting a role for airborne transmission and the potential benefit of respirators (and other precautions designed to prevent inhalation of aerosols) versus surgical masks (mainly effective for reducing exposure to large droplets) to protect healthcare workers, more studies are needed to evaluate the extent of risk posed airborne versus contact and large droplet spray transmission modes. New human challenge-transmission studies should be carefully designed to overcome limitations encountered in the current study. The low secondary attack rate reported herein also suggests that the current challenge-transmission model may no longer be a more promising approach to resolving questions about transmission modes than community-based studies employing environmental monitoring and newer, state-of-the-art deep sequencing-based molecular epidemiological methods.
Cremation based estimates suggest significant under- and delayed reporting of COVID-19 epidemic data in Wuhan and China
Authors: He Mai , Li Li , Dehner Louis P. , Dunn Lucia F.
Published: June 2020

Background

China’s COVID-19 statistics fall outside of recognized and accepted medical norms. Here we estimated the incidence, death and starting time of the COVID-19 outbreak in Wuhan and China based on cremation related information.

Methods

Data sources included literature on COVID-19 in China, official Chinese government figures, state-run and non state-run media reports. Our estimates are based on investigative media reports of crematory operations in Wuhan, which is considered as a common data end point to life. A range of estimates is presented by an exponential growth rate model from lockdown (Jan 23,2020) until the intervention started to show effects, which was estimated 14.5 days after lockdown.

Results

For the cumulative infections and total deaths, under different assumptions of case fatality rates (from 2.5% to 10%) and doubling time 6.4 days, the estimates projected on February 7, 2020 in Wuhan range from 305,000 to 1,272,000 for infections and from 6,811 to 7,223 for deaths - on the order of at least 10 times the official figures (13,603 and 545). The implied starting time of the outbreak is October 2019. The estimates of cumulative deaths, based on both funeral urns distribution and continuous full capacity operation of cremation services up to March 23, 2020, give results around 36,000, more than 10 times of the official death toll of 2,524.

Conclusions

Our study indicates a significant under-reporting in Chinese official data on the COVID-19 epidemic in Wuhan in early February, the critical time for response to the COVID-19 pandemic.
A partial C4photosynthetic biochemical pathway in rice
Authors: Lin Hsiang-Chun , Arrivault Stéphanie , Coe Robert A , Karki Shanta , Covshoff Sarah , Bagunu Efren , Lunn John E. , Stitt Mark , Furbank Robert T. , Hibberd Julian M. , Quick W Paul
Published: June 2020

Introduction of a C4photosynthetic pathway into C3rice (Oryza sativa) requires installation of a biochemical pump that concentrates CO2at the site of carboxylation in modified bundle sheath cells. To investigate the feasibility of this, we generated a quadruple line that simultaneously expresses four of the core C4photosynthetic enzymes from the NADP-malic enzyme subtype, phosphoenolpyruvate carboxylase (ZmPEPC), NADP-malate dehydrogenase (ZmNADP-MDH), NADP-malic enzyme (ZmNADP-ME) and pyruvate phosphate dikinase (ZmPPDK), in a cell-specific manner. This led to enhanced enzyme activity but was largely neutral in its effects on photosynthetic rate and growth. Measurements of the flux of13CO2through photosynthetic metabolism revealed a significant increase in the incorporation of13C into malate, consistent with increased fixation of13CO2via PEP carboxylase in lines expressing the maize PEPC enzyme. We also showed13C labelling of aspartate indicating additional13CO2fixation into oxaloacetate by PEPC and conversion to aspartate by the endogenous aspartate aminotransferase activity. However, there were no significant differences in labelling of 3-phosphoglycerate (3PGA) or phosphoenolpyruvate (PEP) indicating limited carbon flux through C4enzymes into the Calvin-Benson cycle. Crossing the quadruple line with a line with reduced glycine decarboxylase H-protein (OsGDCH) abundance led to a photosynthetic phenotype characteristic of the reducedOsGDCH line and higher labelling of malate, aspartate and citrate. While Kranz anatomy or other anatomical modifications have not yet been installed in these plants to enable a fully functional C4cycle, these results demonstrate for the first-time flux through the carboxylation phase of C4metabolism in transgenic rice containing the key metabolic steps in the C4pathway.
Multicenter point-prevalence evaluation of the utilization and safety of drug therapies for COVID-19
Authors: Rhodes Nathaniel J. , Dairem Atheer , Moore William J. , Shah Anooj , Postelnick Michael J. , Badowski Melissa E. , Michienzi Sarah M. , Borkowski Jaime L. , Polisetty Radhika S. , Fong Karen , Spivak Emily S. , Beardsley James R. , Hale Cory M. , Pallotta Andrea M. , Srinivas Pavithra , Schulz Lucas T.
Published: June 2020

Background

There are currently no FDA-approved medications for the treatment of COVID-19. At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period.

Methods

We conducted a non-interventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19 targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs).

Results

A total of 352 patients from 15 US hospitals were included. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 inhibitors (9%). Five patients (7.5%) were receiving combination therapy. Patients with a history of asthma (14.9% vs. 7%, p = 0.037) and those enrolled in clinical trials (26.9% vs.

3.2%, p< 0.001) were more likely to receive therapy. Among those receiving COVID-19 therapy, eight patients (12%) experienced an ADR, and ADRs were more commonly recognized in patients enrolled in clinical trials (62.5% vs 22%, OR = 5.9, p = 0.028).

Conclusions

While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy including in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 therapies.
Dissection of the Spindle Assembly Checkpoint by Proximity Proteomics
Authors: Garcia Yenni A. , Velasquez Erick F. , Gao Lucy W. , Cheung Keith , Clutario Kevin M. , Williams-Hamilton Taylor , Gholkar Ankur A. , Whitelegge Julian P. , Torres Jorge Z.
Published: June 2020

The spindle assembly checkpoint (SAC) is critical for sensing defective microtubule-kinetochore attachments and tension across the kinetochore and functions to arrest cells in prometaphase to allow time to repair any errors prior to proceeding into anaphase. The SAC has a central role in ensuring the fidelity of chromosome segregation and its dysregulation has been linked to the development of human diseases like cancer. The establishment and maintenance of the SAC relies on multiple protein complexes that are intricately regulated in a spatial and temporal manner through posttranslational modifications like phosphorylation. Over the past few decades the SAC has been highly investigated and much has been learned about its protein constituents and the pathways and factors that regulate its activity. However, the spatio-temporal proximity associations of the core SAC components have not been explored in a systematic manner. Here, we have taken a BioID2 proximity-labeling proteomic approach to define the proximity protein environment for each of the five core SAC proteins BUB1, BUB3, BUBR1, MAD1L1, and MAD2L1 under conditions where the SAC is active in prometaphase. These five protein association maps were integrated to generate the SAC proximity protein network that contains multiple layers of information related to core SAC protein complexes, protein-protein interactions, and proximity associations. Our analysis validated many of the known SAC complexes and protein-protein interactions. Additionally, it uncovered new protein associations that lend insight into the functioning of the SAC and highlighted future areas that should be investigated to generate a comprehensive understanding of the SAC.
When Gaze-Pattern Similarity May Interfere With Future Memory
Authors: Selle Nathalie klein , Gamer Matthias , Pertzov Yoni
Published: June 2020

Human brains have a remarkable ability to separate streams of visual input into distinct memory-traces. It is unclear, however, how this ability relates to the way these inputs are explored via unique gaze-patterns. Moreover, it is yet unknown how motivation to forget or remember influences the gaze similarity and memory relationship. In two experiments, we therefore used a modified directed-forgetting paradigm and either showed blurred versions of the encoded scenes (Experiment 1) or pink noise images (Experiment 2) during attempted memory control. Both experiments demonstrated that higher levels of across-stimulus gaze similarity relate to worse future memory. Although thisacross-stimulus interference effectwas unaffected by motivation, it depended on the perceptual overlap between stimuli and was more pronounced for different scene comparisons, than scene-pink noise comparisons. Intriguingly, these findings echo the pattern similarity effects from the neuroimaging literature and pinpoint a mechanism that could aid the regulation of unwanted memories.
Genetic screen to saturate guard cell signaling network reveals a role of GDP-L-fucose metabolism in stomatal closure
Authors: Waszczak Cezary , Vahisalu Triin , Yarmolinsky Dmitry , Sierla Maija , Zamora Olena , Gavarrón Marina Leal , Palorinne Julia , Carter Ross , Pandey Ashutosh K. , Nuhkat Maris , Carmody Melanie , Puukko Tuomas , Sipari Nina , Lamminmäki Airi , Durner Jörg , Ernst Dieter , Winkler J. Barbro , Paulin Lars , Auvinen Petri , Fleming Andrew J. , Salojärvi Jarkko , Kollist Hannes , Kangasjärvi Jaakko
Published: June 2020

Guard cells regulate plant gas exchange by controlling the aperture of stomatal pores. The process of stomatal closure involves a multi-input signaling network that governs the activity of ion channels, which in turn regulate guard cell turgor pressure and volume. Here we describe a forward genetic screen to identify novel components involved in stomatal movements. Through an ozone-sensitivity approach combined with whole-rosette gas exchange analysis, 130 mutants of established stomatal regulators and 76 novel mutants impaired in stomatal closure were identified. One of the novel mutants was mapped to MURUS1 (MUR1), the first enzyme inde novoGDP-L-fucose biosynthesis. Defects in synthesis or import of GDP-L-Fuc into the Golgi apparatus resulted in impaired stomatal closure to multiple stimuli. Stomatal phenotypes observed inmur1were independent from the canonical guard cell signaling and instead could be related to altered mechanical properties of guard cell walls. Impaired fucosylation of xyloglucan, N-linked glycans and arabinogalactan proteins did not explain the aberrant function ofmur1stomata, however our data suggest that the stomatal phenotypes observed inmur1can at least partially be attributed to defective dimerization of rhamnogalactouronan-II. In addition to providing the genetic framework for future studies on guard cell signaling, our work emphasizes the impact of fucose metabolism on stomatal movement.
The household resistome – frequency of beta-lactamases, class 1 integron and antibiotic resistant bacteria in the domestic environment
Authors: Schages Laura , Lucassen Ralf , Wichern Florian , Kalscheuer Rainer , Bockmühl Dirk
Published: June 2020

The widespread of antibiotic resistance (ABR) among bacteria has become a global health concern for humans, animals and the environment. In this respect, beta-lactams and colistin are of particular interest due to the emergence of multidrug-resistant gram-negative bacteria. Households provide a habitat for bacteria originating from humans, animals, foods, contaminated clothes or other sources in which detergents and biocides are frequently used. Thus, bacteria carrying antibiotic resistance genes (ARGs) might be introduced into private households and may consequently be also released from households to the environment via domestic wastewater. Since data on ABR in the domestic environment is limited, this study aimed to determine the abundance and correlation of beta-lactamase, mobile colistin resistance and class 1 integron genes and to characterize phenotypic resistant strains in private households in Germany. Additionally, the persistence of ABR bacteria to laundering and automated dishwashing was assessed. Shower drains, washing machines and dishwashers were sampled and analyzed using quantitative real-time PCR. Resistant strains were isolated, followed by identification and antibiotic susceptibility testing using VITEK 2. The results show a significantly higher occurrence of ARGs in shower drains compared to washing machines and dishwashers. Several beta-lactamase genes co-occurred and resistance of bacterial isolates correlated positively with genotypic resistance. Laundering and automated dishwashing reduced ABR bacteria significantly and the efficacy increased with increasing duration and temperature. Overall, the domestic environment seems to represent a potential reservoir of beta-lactamase genes and beta-lactam resistant bacteria with shower drains as the dominant source of ABR.

Importance

The abundance of ABR bacteria and ARGs is steadily increasing and has been comprehensively analyzed in natural environments, animals, foods or wastewater treatment plants. Despite of their connection to these environments, private households seem to be neglected. Therefore, the present study investigated shower drains, washing machines and dishwashers as possible sites of ARGs and ABR bacteria. The analysis of the domestic environment as a potential reservoir of resistant bacteria is crucial to determine whether households contribute to the spread of ABR or are a habitat where resistant bacteria from the environment, humans, food or water accumulate.
Molecular epidemiology and clone transmission of carbapenem-resistantAcinetobacter baumanniiin ICU rooms
Authors: Zhang Xiufeng , Li Fangping , Hou Zhuangwei , Awan Furqan , Jiang Hongye , Li Xiaohua , Zeng Zhenling , Lv Weibiao
Published: June 2020

Carbapenem-resistantAcinetobacter baumannii(CRAB) is a major cause of nosocomial infections and hospital outbreaks worldwide, remaining a critical clinical concern. Here we characterized and investigated the phylogenetic relationships of 105 CRAB isolates on intensive care unit surfaces from one hospital in China collected over six years. All strains carriedblaOXA-23,blaOXA-66genes for carbapenem resistance, also had high resistance gene, virulence factor and insertion sequences burdens. Whole-genome sequencing revealed all strains belonged to ST2, the global clone CC2. The phylogenetic analysis based on the core genome showed all isolates was dominated by a single lineage of three clusters and eight different clones. Two clones were popular during the collection time. Using chi-square test to identify the epidemiologically meaningful groupings, we found the significant difference in community structure only present in strains from separation time. The haplotype and median-joining network analysis revealed genetic differences among clusters and changes occurred overtime in the dominating cluster. Our results highlighted substantial multidrug-resistant CRAB burden in hospital ICU environment, demonstrated potential clone outbreak in hospital.
Human mobility and poverty as key drivers of COVID-19 transmission and control
Authors: Yechezkel Matan , Weiss Amit , Rejwan Idan , Shahmoon Edan , Ben-Gal Shachaf , Yamin Dan
Published: June 2020

Background

Applying heavy nationwide restrictions is a powerful method to curtail COVID-19 transmission but poses a significant humanitarian and economic crisis. Thus, it is essential to improve our understanding of COVID-19 transmission and develop more focused and effective strategies. As human mobility drives transmission, data from cell phone devices can be utilized to achieve these goals.

Methods

We analyzed aggregated and anonymized mobility data from the cell-phone devices of>3 million users between February 1, 2020, to May 16, 2020 – in which several movement restrictions were applied and lifted in Israel. We integrated these mobility patterns into age-, risk- and region-structured transmission model. Calibrated to coronavirus incidence in 250 regions covering Israel, we evaluated the efficacy and effectiveness in decreasing mortality of applying localized and temporal lockdowns (stay-at-home order).

Results

Poorer regions exhibited lower and slower compliance with the restrictions. Our transmission model further indicated that individuals from poverty areas were associated with high transmission rates. Model projections suggested that, counterintuitively, school closure has an adverse effect and increases COVID-19 mortality in the long run, while interventions focusing on the elderly are the most efficient. We also found that applying localized and temporal lockdowns during regional outbreaks reduce mortality compared to nationwide lockdowns. These trends were consistent across vast ranges of epidemiological parameters, possible seasonal forcing, and even when we assumed that vaccination would be commercially available in 1-3 years.

Conclusions

More resources should be devoted to helping impoverished regions. Utilizing cellphone data despite being anonymized and aggregated can help policymakers worldwide identify hotspots and apply designated strategies against future COVID-19 outbreaks.
Characteristics and risk factors for COVID-19 diagnosis and adverse outcomes in Mexico: an analysis of 89,756 laboratory–confirmed COVID-19 cases
Authors: Giannouchos Theodoros V , Sussman Roberto A , Mier Odriozola José Manuel , Poulas Konstantinos , Farsalinos Konstantinos
Published: June 2020

Background

There is insufficient information about risk factors for COVID-19 diagnosis and adverse outcomes from low and middle-income countries (LMICs).

Objectives

We estimated the association between patients’ characteristics and COVID-19 diagnosis, hospitalization and adverse outcome in Mexico.

Methods

This retrospective case series used a publicly available nation-level dataset released on May 31, 2020 by the Mexican Ministry of Health, with patients classified as suspected cases of viral respiratory disease. Patients with COVID-19 were laboratory-confirmed. Their profile was stratified by COVID-19 diagnosis or not. Differences among COVID-19 patients based on two separate clinical endpoints, hospitalization and adverse outcome, were examined. Multivariate logistic regressions examined the associations between patient characteristics and hospitalization and adverse outcome.

Results

Overall, 236,439 patients were included, with 89,756 (38.0%) being diagnosed with COVID-19. COVID-19 patients were disproportionately older, males and with increased prevalence of one or more comorbidities, particularly diabetes, obesity, and hypertension. Age, male gender, diabetes, obesity and having one or more comorbidities were independently associated with laboratory-confirmed COVID-19. Current smokers were 23% less likely to be diagnosed with COVID-19 compared to non-smokers. Of all COVID-19 patients, 34.8% were hospitalized and 13.0% experienced an adverse outcome. Male gender, older age, having one or more comorbidities, and chronic renal disease, diabetes, obesity, COPD, immunosuppression and hypertension were associated with hospitalization and adverse outcome. Current smoking was not associated with adverse outcome.

Conclusion

This largest ever case series of COVID-19 patients identified risk factors for COVID-19 diagnosis, hospitalization and adverse outcome. The findings could provide insight for the priorities the need to be set, especially by LMICs, to tackle the pandemic.
Estimating the effect of lipids on IGF axis and subsequent breast cancer risk
Authors: Tan Vanessa Y , Bull Caroline J , Biernacka Kalina M , Teumer Alexander , Corbin Laura , Dudding Tom , Sanderson Eleanor , Qi Qibin , Kaplan Robert C , Rotter Jerome I , Friedrich Nele , Völker Uwe , Mayerle Julia , Perks Claire M , Holly Jeff MP , Timpson Nicholas J
Published: June 2020

Circulating lipids have been associated with breast cancer (BCa). This association may, in part, be due to an effect of lipids on insulin-like growth factors (IGFs), which have been reliably associated with BCa. In two-sample Mendelian randomization (MR) analyses, we found that low density lipoprotein (LDL-C) was associated with IGFBP-3 (beta:0.08 SD; 95%CI:0.02,0.15; p = 0.01, per SD increase in LDL-C) and IGFBP-3 was associated with postmenopausal BCa (OR:1.09; 95%CI:1.00,1.19; p = 0.05, per SD increase in IGFBP-3). We also found that triglycerides were associated with IGF-I (beta:-0.13SD; 95%CI:-0.22,-0.03, per SD increase in triglycerides) and that IGF-I was associated with overall BCa (OR:1.10;95%CI:1.02,1.18, per SD increase in IGF-I). Taken together, these results suggest that IGFBP-3 may be a potential causal step between LDL-C and postmenopausal BCa and IGF-I a potential causal for triglycerides. Our two-step MR results build on evidence linking circulating lipids and IGFs with BCa, however, multivariable MR analyses are currently unable to support this relationship due to weak instruments.
First environmental surveillance for the presence of SARS-CoV-2 RNA in wastewater and river water in Japan
Authors: Haramoto Eiji , Malla Bikash , Thakali Ocean , Kitajima Masaaki
Published: June 2020

Wastewater-based epidemiology is a powerful tool to understand the actual incidence of coronavirus disease 2019 (COVID-19) in a community because severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, can be shed in the feces of infected individuals regardless of their symptoms. The present study aimed to assess the presence of SARS-CoV-2 RNA in wastewater and river water in Yamanashi Prefecture, Japan, using four quantitative and two nested PCR assays. Influent and secondary-treated (before chlorination) wastewater samples and river water samples were collected five times from a wastewater treatment plant and three times from a river, respectively, between March 17 and May 7, 2020. The wastewater and river water samples (200–5,000 mL) were processed by using two different methods: the electronegative membrane-vortex (EMV) method and the membrane adsorption-direct RNA extraction method. Based on the observed concentrations of indigenous pepper mild mottle virus RNA, the EMV method was found superior to the membrane adsorption-direct RNA extraction method. SARS-CoV-2 RNA was successfully detected in one of five secondary-treated wastewater samples with a concentration of 2.4 × 103 copies/L by N_Sarbeco qPCR assay following the EMV method, whereas all the influent samples were tested negative for SARS-CoV-2 RNA. This result could be attributed to higher limit of detection for influent (4.0 × 103–8.2 × 104 copies/L) with a lower filtration volume (200 mL) compared to that for secondary-treated wastewater (1.4 × 102–2.5 × 103 copies/L) with a higher filtration volume of 5,000 mL. None of the river water samples tested positive for SARS-CoV-2 RNA. Comparison with the reported COVID-19 cases in Yamanashi Prefecture showed that SARS-CoV-2 RNA was detected in the secondary-treated wastewater sample when the cases peaked in the community. This is the first study reporting the detection of SARS-CoV-2 RNA in wastewater in Japan.
‘Drawing on Wisdom to Cope with Adversity:’ A Systematic Review Protocol of Older Adults’ Mental and Psychosocial Health During Acute Respiratory Disease Propagated-Type Epidemics and Pandemics (COVID-19, SARS-CoV, MERS, and Influenza)
Authors: Aravena Jose M. , Aceituno Cristopher , Nyhan Kate , Shi Kewei , Vermund Sten , Levy Becca R.
Published: June 2020

Background

Mental health has become one of the fundamental priorities during the COVID-19 pandemic. Situations like physical distancing as well as being constantly tagged as the most vulnerable group could expose older adults to mental and psychosocial burdens. Nonetheless, there is little clarity about the impact of the COVID-19 pandemic or similar pandemics in the past on the mental illness, wellbeing, and psychosocial health of the older population compared to other age groups.

Objectives

To describe the patterns of older adults’ mental and psychosocial health related to acute respiratory disease propagated-type epidemics and pandemics and to evaluate the differences with how other age groups respond.

Eligibility criteria

quantitative and qualitative studies evaluating mental illness, wellbeing, or psychosocial health outcomes associated with respiratory propagated epidemics and pandemics exposure or periods (COVID-19, SARS-CoV, MERS, and Influenza) in people 65 years or older.

Data source

Original articles published until June 1st, 2020, in any language searched in the electronic healthcare and social sciences database: MEDLINE, Embase, CINAHL, PsycINFO, Scopus, WHO Global literature on coronavirus disease database, China National Knowledge Infrastructure (中国 知网 –CNKI). Furthermore, EPPI Centre’s COVID-19 living systematic map and the publicly available publication list of the COVID-19 living systematic review will be incorporated for preprints and recent COVID-19 publications.

Data extraction

Two independent reviewers will extract predefined parameters. The risk of bias will be assessed.

Data synthesis

Data synthesis will be performed according to study type and design, type of epidemic and pandemic, types of outcomes (mental health and psychosocial outcomes), and participant characteristics (e.g., sex, race, age, socioeconomic status, food security, presence of dependency in daily life activities independent/dependent older adults). Comparison between sex, race, and other age groups will be performed qualitatively, and quantitatively if enough data is available. The risk of bias and study heterogeneity will be reported for quantitative studies.

Conclusion

This study will provide information to take actions to address potential mental health difficulties during the COVID-19 pandemic in older adults and to understand responses on this age group. Furthermore, it will be useful to identify potential groups that are more vulnerable or resilient to the mental-health challenges of the current worldwide pandemic.
ENVIRONMENTAL SAFETY EVALUATION OF THE PROTECTION AND ISOLATION SYSTEM FOR PATIENTS WITH COVID-19
Authors: Almeida Quadros Claudio , Bezerra Di Medeiros Leal Maria Carolina , Baptista Sobrinho Carlos de Almeida , Vasques Nonaka Carolina Kymie , Freitas Souza Bruno Solano de , Milan-Mattos Juliana Cristina , Catai Aparecida Maria , Pires Di Lorenzo Valéria Amorim , Ferreira Antonio Gilberto
Published: June 2020

Background

SARS-CoV-2 has high transmissibility through respiratory droplets and aerosol, making COVID-19 a worldwide pandemic. In its severe form, patients progress to respiratory failure. Non-invasive mechanical ventilation restrictions and early orotracheal intubation have collapsed health systems due to insufficient intensive care unit beds and mechanical ventilators. COVID-19 dedicated healthcare professionals have high infection rates. This publication describes experimental testing of the Protection and Isolation System for Patients with COVID-19 (PISP/COVID-19).

Method

PISP/COVID-19 is a disposable transparent polyethylene plastic that covers the patient’s entire hospital bed, with its internal air aspirated by the hospital’s vacuum system attached to a microparticle filter. Experiments validated PISP/COVID-19’s ability to block aerosolized microparticles dissemination. Caffeine was used as a molecular marker, with leakage evaluation through sensors analysis using nuclear magnetic resonance spectroscopy. The biological marker was synthetic SARS-CoV-2 RNA, using Reverse Transcription Polymerase Chain Reaction (RT-PCR) as the detection method.

Results

PISP/COVID-19 was effective against molecular and biological markers environmental dispersion in simulations of non-invasive ventilation, high-flow nasal cannula oxygen and mechanical ventilation isolation. Caffeine was not detected in any of the sensors positioned at points outside the PISP/COVID-19. The ability of PISP/COVID-19 to retain virus particles and protect the surrounding environment was confirmed by detection and gradients quantification of synthetic SARS-CoV-2 RNA by RT-PCR.

Conclusion

PISP/COVID-19 was effective in the retention of the molecular and biological markers in all tested simulations. Considering the current pandemic, PISP/COVID-19 might increase the use of non-invasive ventilation, high-flow nasal cannula oxygen and provide additional protection to healthcare professionals.
Knockdown of the E3 Ubiquitin ligase UBR5 and its role in skeletal muscle anabolism
Authors: Turner Daniel C. , Hughes David C. , Baehr Leslie M. , Seaborne Robert A. , Viggars Mark , Jarvis Jonathan C. , Gorski Piotr P. , Stewart Claire E. , Owens Daniel J. , Bodine Sue C. , Sharples Adam P.
Published: June 2020

UBR5 is an E3-ubiquitin-ligase positively associated with anabolism, hypertrophy and recovery from atrophy in skeletal muscle. The precise mechanisms underpinning UBR5’s role in the regulation of skeletal muscle mass remain unknown. The present study aimed to elucidate these mechanisms by silencing the UBR5 genein-vitroandin-vivo. The siRNA-induced reduction (−77%) in UBR5 gene expression in human myotubes was prevented by mechanical loading, suggesting that UBR5 gene expression may be regulated via mechano-transduction signalling. Therefore, we electroporated a UBR5-RNAi plasmid into mouse tibialis anterior musclein-vivoto investigate the impact of reduced UBR5 on mechano-transduction signalling MEK/ERK/p90RSK and Akt/p70S6K/4E-BP1/rpS6 pathways. Seven days post UBR5 RNAi electroporation, while reductions in overall muscle mass were not detected, mean CSA of GFP-positive fibers was reduced (−9.5%) and the number of large fibers was lower versus the control. Importantly, UBR5-RNAi significantly reduced total RNA, muscle protein synthesis, ERK1/2 and Akt phosphorylation. Whilst p90RSK phosphorylation significantly increased, total p90RSK protein levels demonstrated a 45% reduction with UBR5-RNAi. Finally, these early signalling events after 7 days of UBR5 knockdown culminated in significant reductions in muscle mass (−4.6%) and larger reductions in fiber CSA (−18.5%) after 30 days. This was associated with increased levels of the phosphatase, PP2Ac, and inappropriate chronic elevation of p70S6K and rpS6 between 7 and 30 days, and corresponding reductions in eIF4e. This study demonstrates UBR5 plays an important role in anabolism/hypertrophy, whereby knockdown of UBR5 culminates in skeletal muscle atrophy.
Crowdsourcing assessment of maternal blood multi-omics for predicting gestational age and preterm birth
Authors: Tarca Adi L. , Pataki Bálint Ármin , Romero Roberto , Sirota Marina , Guan Yuanfang , Kutum Rintu , Gomez-Lopez Nardhy , Done Bogdan , Bhatti Gaurav , Yu Thomas , Andreoletti Gaia , Chaiworapongsa Tinnakorn ,   The DREAM Preterm Birth Prediction Challenge Consortium, Hassan Sonia S. , Hsu Chaur-Dong , Aghaeepour Nima , Stolovitzky Gustavo , Csabai Istvan , Costello James C.
Published: June 2020

Identification of pregnancies at risk of preterm birth (PTB), the leading cause of newborn deaths, remains challenging given the syndromic nature of the disease. We report a longitudinal multi-omics study coupled with a DREAM challenge to develop predictive models of PTB. We found that whole blood gene expression predicts ultrasound-based gestational ages in normal and complicated pregnancies (r=0.83), as well as the delivery date in normal pregnancies (r=0.86), with an accuracy comparable to ultrasound. However, unlike the latter, transcriptomic data collected at <37 weeks of gestation predicted the delivery date of one third of spontaneous (sPTB) cases within 2 weeks of the actual date. Based on samples collected before 33 weeks in asymptomatic women we found expression changes preceding preterm prelabor rupture of the membranes that were consistent across time points and cohorts, involving, among others, leukocyte-mediated immunity. Plasma proteomic random forests predicted sPTB with higher accuracy and earlier in pregnancy than whole blood transcriptomic models (e.g. AUROC=0.76 vs. AUROC=0.6 at 27-33 weeks of gestation).
Kinetic Modeling of West Nile Virus Fusion Indicates an Off-pathway State
Authors: Park Abraham , Rawle Robert J.
Published: June 2020

West Nile virus (WNV) is a prominent mosquito-borne flavivirus that causes febrile illness in humans. To infect host cells, WNV virions first bind to plasma membrane receptors, then initiate membrane fusion following endocytosis. The viral transmembrane E protein, triggered by endosomal pH, catalyzes fusion while undergoing a dimer-to-trimer transition. Previously, single-particle WNV fusion data was interrogated with a stochastic cellular automaton simulation, which modeled the E proteins during the fusion process. The results supported a linear fusion mechanism, with E protein trimerization being rate-limiting. Here, we present corrections to the previous simulation, and apply them to the WNV fusion data. We observe that a linear mechanism is no longer sufficient to fit the data. Instead, an off-pathway state is necessary; these results are corroborated by chemical kinetics modeling. When compared with a similar Zika virus fusion model, this suggests that off-pathway fusion mechanisms may characterize flaviviruses more broadly.