bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer of mitochondria and endosomes between cells by gap junction internalization
Authors: Norris Rachael P.
Published: April 2021

Intercellular organelle transfer has been documented in several cell types and has been proposed to be important for cell‐cell communication and cellular repair. However, the mechanisms by which organelle transfer occurs are uncertain. Recent studies indicate that the gap junction protein, connexin 43 (Cx43), is required for mitochondrial transfer but its specific role is unknown. Using three‐dimensional electron microscopy and immunogold labeling of Cx43, this report shows that whole organelles including mitochondria and endosomes are incorporated into double‐membrane vesicles, called connexosomes or annular gap junctions, that form as a result of gap junction internalization. These findings demonstrate a novel mechanism for intercellular organelle transfer mediated by Cx43 gap junctions.
Survey of group A plasma and low‐titer group O whole blood use in trauma resuscitation at adult civilian level 1 trauma centers in the US
Authors: Yazer Mark H. , Spinella Philip C. , Anto Vincent , Dunbar Nancy M.
Published: April 2021

Background

Recently revisited products like low‐titer group O whole blood (LTOWB) and novel applications of group A as a universal donor of plasma are being used for trauma resuscitation. A survey of American Level 1 trauma centers was performed to elucidate the extent to which these products are currently employed.

Methods

A survey was written that probed into the current use of blood products in trauma resuscitation with specific emphasis on LTOWB and group A plasma. A list of adult civilian Level 1 trauma centers in the continental USA was obtained from two public surgery and trauma focused websites. An email was then sent to each center's transfusion service medical director or laboratory manager providing them with a link to the online survey.

Results

Responses were received from 103/187 (55%) adult civilian Level 1 trauma centers. For the resuscitation of trauma patients, group A plasma was used at 94/103 (91%) centers, while LTOWB was used at 43/103 (42%) centers. There were 39/103 (38%) centers that used both products. At 62/94 (66%) of the centers that used group A plasma, there was no limit on the number of units that could be administered, while an unlimited number of LTOWB units could be used at 5/43 (12%) of the centers that used LTOWB. RhD‐positive LTOWB could be transfused to RhD‐negative or RhD‐type unknown females of childbearing potential at 22/43 (51%) of centers.

Conclusion

The use of group A plasma and LTOWB in trauma is increasing at American Level 1 trauma centers.
Comparison of sedation quality and safety of detomidine and romifidine as a continuous rate infusion for standing elective laparoscopic ovariectomy in mares
Authors: Lawless Shauna P. , Moorman Valerie J. , Hendrickson Dean A. , Mama Khursheed R.
Published: April 2021

Objective

To compare efficacy and safety of a continuous rate infusion of detomidine hydrochloride and romifidine hydrochloride for standing elective bilateral laparoscopic ovariectomy in mares.

Study Design

Blinded, randomized prospective clinical study.

Animals

Eighteen healthy mares presenting for elective bilateral ovariectomy

Methods

Mares were randomly assigned to one of two sedation protocols. Prior to surgery, baseline head height, heart rate, respiratory rate, and postural sway were recorded. An IV loading dose of α2‐agonist (46 μg/kg romifidine or 13.9 μg/kg detomidine) was administered. Standing sedation was maintained with a continuous rate infusion of the respective α2‐agonist (126 μg/kg/h romifidine or 37.8 μg/kg/h detomidine). Intraoperative measurements included respiratory rate, heart rate, head height, postural sway, and response to surgical stimulus. Postoperatively, fecal output was recorded, and pain scoring was performed using composite pain score and visual analog scales.

Results

Three of 18 horses required additional α‐2 agonists: one detomidine and two romifidine and butorphanol. Head height during surgery was lower (p < .001) in mares receiving detomidine. Postural sway around the vertical axis was greater in mares sedated with detomidine rather than romifidine (p = .013). No differences were detected in intraoperative heart rate, postoperative pain scores or postoperative fecal output between sedation techniques.

Conclusion

Comparable scores for surgical stimulation and sedation were measured in both sedation groups. No differences in postoperative analgesia or manure production were identified.

Clinical Significance

Romifidine appears suitable as an alternative to detomidine and may limit ataxia and head drop in sedated horses.
Toll‐like receptor activation of equine mesenchymal stromal cells to enhance antibacterial activity and immunomodulatory cytokine secretion
Authors: Pezzanite Lynn M. , Chow Lyndah , Johnson Valerie , Griffenhagen Gregg M. , Goodrich Laurie , Dow Steven
Published: April 2021

Objective

To evaluate effects of Toll‐like and nucleotide‐binding oligomerization domain (NOD)‐like receptor (TLR, NLR) ligand stimulation of equine mesenchymal stromal cells (MSCs) on antibacterial and immunomodulatory properties in vitro.

Study Design

Controlled laboratory study.

Sample Population

Equine bone‐marrow‐derived MSCs (three horses).

Methods

MSCs were stimulated with TLR (polyinosinic:polycytidylic acid [pIC] and lipopolysaccharide [LPS]) and NLR agonists (γ‐d‐Glu‐mDAP [IE‐DAP]) for 2 h, and plated at 1 × 105 cells/well 24 h. MSC‐conditioned media (MSC‐CM) were collected and assessed for antimicrobial peptide cathelicidin/LL‐37 production, bactericidal action against multidrug‐resistant planktonic and biofilm Staphylococcus aureus and neutrophil phagocytosis. Bacterial growth was measured by plating bacteria and counting viable colonies, reading culture absorbance, and live‐dead staining with confocal microscopy imaging. Following initial comparison of activating stimuli, TLR3‐agonist pIC protocols (cell density during activation and plating, culture time, %serum) were further optimized for bactericidal activity and secretion of interleukin‐8 (IL‐8), monocyte‐chemoattractant‐protein (MCP‐1), and cathelicidin/LL37.

Results

MSCs stimulation with pIC (p = .004) and IE‐DAP (p = .03) promoted increased bactericidal activity, evidenced by reduced viable planktonic colony counts. PIC stimulation (2 × 106 cells/ml, 2 h, 10 μg/ml) further suppressed biofilm formation (p = .001), enhanced neutrophil bacterial phagocytosis (p = .009), increased MCP‐1 secretion (p < .0001), and enhanced cathelicidin/LL‐37 production, which was apparent when serum concentration in media was reduced to 1% (p = .01) and 2.5% (p = .05).

Conclusion

TLR‐3 pIC MSCs activation was most effective to enhance antibacterial and cytokine responses, which were affected by serum reduction.

Clinical Significance

In vitro TLR‐3 activation of equine MSCs tested here may be a strategy to improve antibacterial properties of MSCs to treat antibiotic‐resistant infections.
Influence of normograde versus retrograde catheterization of bile ducts in dogs treated for gallbladder mucocele
Authors: Putterman Allison B. , Selmic Laura E. , Kindra Cameron , Duffy Daniel J. , Risselada Marije , Phillips Heidi
Published: April 2021

Objective

To determine the influence of normograde (NG) versus retrograde (RG) catheterization of the cystic duct and common bile duct (CBD) in dogs with gallbladder mucoceles (GBM) treated with open cholecystectomy.

Study design

Retrospective study.

Animals

Dogs (n= 117) with GBM.

Methods

Medical records were reviewed for signalment, history, clinical laboratory and diagnostic imaging findings, details of surgery including catheterization method, complications, and outcome. Long‐term follow‐up data were obtained by telephone or electronic communication. Relationships between catheterization method and clinical variables and outcome were evaluated.

Results

Dogs catheterized RG were more likely to experience any postoperative complication (p= .0004) including persistence of gastrointestinal signs (p= .0003). Survival to discharge and long‐term survival did not differ by group (p= .23 andp= .49). Total bilirubin (TB) decreased by 70.3% after NG catheterization compared to 39.1% after RG catheterization (p= .03) and increased in 14.9% dogs catheterized NG and 38.0% dogs catheterized RG (p= .004). The presence of a diplomate surgeon at surgery resulted in decreased incidences of any perioperative or postoperative complication (p= .003 andp= .05).

Conclusion

Retrograde catheterization was associated with more postoperative concerns than NG catheterization, but similar survival times. Surgery should be performed by diplomates experienced in biliary surgery to minimize complications.

Clinical significance

Although both NG and RG techniques to catheterize the cystic duct and CBD are options for treatment of GBM with low mortality, results of this study provide some evidence to recommend NG over RG catheterization.
Kink and anti-kink wave solutions for the generalized KdV equation with Fisher-type nonlinearity
Authors: Kocak Huseyin
Published: April 2021

This paper proposes a new dispersion-convection-reaction model, which is called the gKdV-Fisher equation, to obtain the travelling wave solutions by using the Riccati equation method. The proposed equation is a third-order dispersive partial differential equation combining the purely nonlinear convective term with the purely nonlinear reactive term. The obtained global and blow-up solutions, which might be used in the further numerical and analytical analyses of such models, are illustrated with suitable parameters.
Uncertainty Estimation of Biomedical Oximeters: Proposal for an Experimental Test-Bench
Authors: Marchionni Paolo , Nobile Stefano , Carnielli Virgilio P. , Scalise Lorenzo
Published: April 2021

Paramagnetic oximeters are frequently used in clinical practice to measure and titrate the fraction of inspired oxygen (FiO2) administered to a hypoxic patient. Newborns are prone to several diseases leading to hypoxia but also to oxidative damage, therefore a precise measurement of administered oxygen is of paramount importance. In this study, we evaluated and compared the performance of four commonly used gas analyzers at a Neonatal Unit. A paramagnetic gas analyzer was considered the standard for reference. Gas mixing performed by blenders was also evaluated. We first assessed the stability and composition of O2 and medical air. A settling time study was conducted to estimate a steady-state. Results show how tested blenders underestimated the real measures when FiO2 was <50% and overestimated them when FiO2 ≥50%. In all the tested oximeters the FiO2 was underestimated by 1.18%, but the overall agreement with the gold standard was very good.
Open Source Filament Diameter Sensor for Recycling, Winding, and Additive Manufacturing Machines
Authors: Petsiuk Aliaksei , Pearce Joshua M.
Published: April 2021

To overcome the challenge of upcycling plastic waste into three-dimensional (3D) printing filament in the distributed recycling and additive manufacturing systems, this study designs, builds, tests, and validates an open-source filament diameter sensor for recycling and winding machines. The modular system for multi-axis optical control of the diameter of the recycled 3D-printer filament makes it possible to scan part of the surface of the processed filament, save the history of measurements along the entire length of the spool, as well as mark defective areas. The sensor is developed as an independent module and integrated into a recyclebot. It was tested on different kinds of polymers (acrylonitrile butadiene styrene (ABS), polylactide (PLA)), different sources of plastic, and different colors including clear plastic. The results were compared with the manual measurements, and the measurements obtained with a one-dimensional digital light caliper. The results found that the developed open-source filament sensing method allows users to obtain significantly more information in comparison with basic one-dimensional light sensors and using the received data not only for more accurate diameter measurements but also for a detailed analysis of the recycled filament surface. This could help to expand the use of plastic recycling technologies in the manufacturing community. The availability of tools for possible texture analysis could also stimulate the growth of composite materials creation. The presented system can greatly enhance the user possibilities and serve as a starting point for a complete recycling control system that will regulate motor parameters to achieve the desired filament diameter with acceptable deviations and even control the extrusion rate on a printer to recover from filament irregularities.
Optimization of Translational Flexure Joints Using Corrugated Units Under Stress Constraints
Authors: Li Canran , Wang Nianfeng , Yue Fan , Zhang Xianmin
Published: April 2021

When optimizing corrugated flexure (CF) joints, most approaches for calculating the maximum stress on the CF beam depend on finite element analysis (FEA). The current paper introduces the design optimization for joints using CF units under stress constraints. The stress state is solved; based on that, the maximum displacement under stress constraints is deduced. The natural frequency formula of the translational joint is further derived from the results of the stiffness matrix. The stage configurations corresponding to the maximum displacement are optimized by restricting the off-axis/axial stiffness ratio and natural frequency of the joint. The optimal results of different types are validated by FEA and experiments.
Experimental Study on a New Small-Scale Absorption System: Response Surface and Inverse Analyses
Authors: Singh Gaurav , Das Ranjan
Published: April 2021

In this paper, a new small-scale lithium bromide (LiBr)-water absorption system consisting water-cooled absorber and air-cooled condenser is experimentally studied. For compactness, the heat exchangers for evaporator, absorber, and generator are made helical-coiled type, whereas based on the water availability and load requirements, condenser is air-cooled. Accurate empirical correlations for thermal load and evaporator temperature against the concerning system driving factors have been reported. Response surface analyses of the performance parameters are studied with respect to LiBr concentration, temperature of generator, and mass flowrate of hot water. Using experimental data, the estimation of overall heat transfer coefficient (U) and its variation with system driving factors is quantified. The error margin between theoretical and actual pressure loss is limited within 5%. Next, a multi-objective inverse analysis of the developed system is done to simultaneously retrieve the required LiBr concentration, mass flowrate of hot water, and vapor generator temperature to derive a desired cooling performance demand from the system. The physics related to salt concentration and generator temperature in governing U values are reported. It can be established that the necessary operational parameters can be predicted by the present multi-objective inverse method to meet the necessary thermal load and temperature demands within an accuracy level of 6% and 5%, respectively.
Thermodynamic Modeling of Heat Engines Including Heat Transfer and Compression–Expansion Irreversibilities
Authors: Osorio Julian D. , Rivera-Alvarez Alejandro , Abakporo Obie I. , Ordonez Juan C. , Hovsapian Rob
Published: April 2021

In this work, a thermodynamic model based on an endoreversible engine approach is developed to analyze the performance of heat engines operating under different thermodynamic cycles. The model considers finite heat transfer rate, variable heat source and sink temperatures, and irreversibilities associated with the expansion and compression. Expressions for the maximum power and efficiency at maximum power output are obtained as a function of hot and cold reservoir temperatures, the equivalent isentropic efficiency of compression and expansion components, and the effective conductance ratio between heat exchangers. In all cases, the Curzon–Ahlborn efficiency is retrieved at constant reservoir temperatures and neglected compression–expansion irreversibilities. The proposed model allows assessing the effect of isentropic efficiencies and heat exchanger design and operation characteristics for different thermodynamic cycles.
Acoustic effects of non-transparent and transparent face coverings
Authors: Atcherson Samuel R. , McDowell B. Renee , Howard Morgan P.
Published: April 2021

The widespread use of face coverings during the COVID-19 pandemic has created communication challenges for many individuals, particularly for those who are deaf or hard of hearing and for those who must speak through masks in suboptimal conditions. This study includes some newer mask options as well as transparent masks to help those who depend on lipreading and other facial cues. The results corroborate earlier published results for non-transparent masks, but transparent options have greater attenuation, resonant peaks, and deflect sounds in ways that non-transparent masks do not. Although transparent face coverings have poorer acoustic performance, the presence of visual cues remains important for both verbal and non-verbal communication. Fortunately, there are creative solutions and technologies available to overcome audio and/or visual barriers caused by face coverings.
Agreement Between Different Days of activPAL and Actigraph GT3X Measurement of Sedentary Behavior and Physical Activity During the School Hours in Elementary Children
Authors: Barboza Luciana L.S. , Gandarela Larissa , Santana Josefa Graziele S. , Silva Ellen Caroline M. , Machado Elondark S. , Silva Roberto Jerônimo S. , Gomes Thayse N. , Silva Danilo R.
Published: April 2021

Introduction: The authors’ objective was to identify the minimum number of days required to measure sedentary behavior and physical activity in children during school hours. Methods: Fifty-three children from four classes of the second year of elementary school in a public school in Brazil were selected. Sedentary behavior and physical activity were evaluated using activPAL in the thigh and ActiGraph GT3X on the hip. The devices were used for 4 days during the 4 hr of school. Intraclass correlation coefficient (ICC) and Bland–Altman plots were used for statistical analysis (p < .05). Results: For sedentary/stationary behavior indicators, 1 day showed good agreement with 4 days (sitting time, ICC = .89; bias [limits of agreement 95%, LA95%] = 1.6 [45.1 to −41.9], standing time, ICC = .93; bias [LA95%] 1.1 [30.2 to −28.0], and stationary behavior, ICC = .56; bias [LA95%] = 0.2 [37.2 to −36.7]). However, 2 days were necessary for good agreement, with 4 days for physical activity indicators (walking time, ICC = .91; bias [LA95%] = 1.1 [12.0 to −9.7], light physical activity, ICC = .97; bias [LA95%] = 0.3 [7.6 to −7.0], moderate physical activity, ICC = .93; bias [LA95%] = 0.3 [2.3 to −1.6], and vigorous physical activity, ICC = .93; bias [LA95%] = 0.3 [3.1 to −2.5]). Conclusion: Therefore, 1 evaluation day seems enough to obtain representative data of school sedentary/stationary behavior, while 2 days are necessary for the evaluation of physical activity indicators during school hours.
Estimates of Physical Activity in Older Adults Using the ActiGraph Low-Frequency Extension Filter
Authors: Hicks Hilary , Laffer Alexandra , Meyer Kayla , Watts Amber
Published: April 2021

As a default setting, many body-worn research-grade activity monitors rely on software algorithms developed for young adults using waist-worn devices. ActiGraph offers the low-frequency extension (LFE) filter, which reduces the movement threshold to capture low acceleration activity, which is more common in older adults. It is unclear how this filter changes activity estimates and whether it is appropriate for all older adults. The authors compared activity estimates with and without the LFE filter on wrist-worn devices in a sample of 34 older adults who wore the ActiGraph GT9X on their nondominant wrist for 7 days in a free-living environment. The authors used participant characteristics to predict discrepancy in step count estimates generated with and without the LFE filter to determine which individuals are most accurately characterized. Estimates of steps per minute were higher (M = 21,SD = 1), and more activity was classified as moderate to vigorous intensity (M = 5.03%,SD = 3.92%) with the LFE filter (M = 11,SD = 1;M = 4.27%,SD = 3.52%) versus without the LFE filter (allps < .001). The findings suggest that axes-based variables should be interpreted with caution when generated with wrist-worn data, and future studies should develop separate wrist and waist-worn standard estimates in older adults. Participation in a greater amount of moderate to vigorous intensity physical activity predicted a larger discrepancy in step counts generated with and without the filter (p < .009), suggesting that the LFE filter becomes increasingly inappropriate for use in highly active older individuals.
Impact of Flexible Work Arrangements, Self-Efficacy, and Barriers on Daily Physical Activity Among University Staff
Authors: Borowski Shelby , Savla Jyoti , Zvonkovic Anisa M.
Published: April 2021

Background: Little is known about the link between flexible work arrangements and health behaviors, such as physical activity. This study aimed to explore how self-efficacy and daily barriers to physical activity influence daily levels of physical activity on workdays when university staff members used a flexible work arrangement (flextime or telework). Methods: Full-time university staff employees (N = 61, mean age = 41; 89% female) participated in this daily diary study. Participants completed an initial survey followed by daily surveys over the course of one workweek, resulting in 281 diary days. Results: The most frequently reported barriers to physical activity were as follows: lack of time, feeling tired, and not enough motivation. Multilevel models revealed that as the number of barriers increased, minutes of physical activity significantly decreased. Self-efficacy was not significantly related to daily physical activity. Participants reported fewer minutes of physical activity on flextime workdays compared to days when a flexible work arrangement was not used (ie, traditional workday). Daily use of a flexible work arrangement did not moderate the association between barriers and physical activity. Conclusions: This study illustrated the influence of daily barriers and flextime workdays on physical activity levels, which can inform workplace health programs for university staff.
Reduced MC4R signaling alters nociceptive thresholds associated with red hair
Authors: Robinson Kathleen C. , Kemény Lajos V. , Fell Gillian L. , Hermann Andrea L. , Allouche Jennifer , Ding Weihua , Yekkirala Ajay , Hsiao Jennifer J. , Su Mack Y. , Theodosakis Nicholas , Kozak Gabor , Takeuchi Yuichi , Shen Shiqian , Berenyi Antal , Mao Jianren , Woolf Clifford J. , Fisher David E.
Published: April 2021

In the red-haired background, altered pain thresholds exist and are explained by distinct OPRM1/MC4R signaling.
Two sides of the same coin: Beneficial and detrimental consequences of range adaptation in human reinforcement learning
Authors: Bavard Sophie , Rustichini Aldo , Palminteri Stefano
Published: April 2021

Paradoxical consequences of range adaptation in human reinforcement learning: The easier the task, the higher the learning bias.
Coupling light to a nuclear spin gas with a two-photon linewidth of five millihertz
Authors: Katz Or , Shaham Roy , Firstenberg Ofer
Published: April 2021

Realization of coherent coupling between light and long-lived noble-gas spins opens new routes to quantum optics and sensing.
Ligand recognition, unconventional activation, and G protein coupling of the prostaglandin E
2
receptor EP2 subtype
Authors: Qu Changxiu , Mao Chunyou , Xiao Peng , Shen Qingya , Zhong Ya-Ni , Yang Fan , Shen Dan-Dan , Tao Xiaona , Zhang Huibing , Yan Xu , Zhao Ru-Jia , He Junyan , Guan Ying , Zhang Chao , Hou Guihua , Zhang Peng-Ju , Hou Guige , Li Zijian , Yu Xiao , Chai Ren-Jie , Guan You-Fei , Sun Jin-Peng , Zhang Yan
Published: April 2021

Structures of prostaglandin receptor EP2 revealed its agonists’ selectivity and G protein coupling mechanism.
Enabling propagation of anisotropic polaritons along forbidden directions via a topological transition
Authors: Duan J. , Álvarez-Pérez G. , Voronin K. V. , Prieto I. , Taboada-Gutiérrez J. , Volkov V. S. , Martín-Sánchez J. , Nikitin A. Y. , Alonso-González P.
Published: April 2021

The propagation of anisotropic polaritons along previously forbidden directions through a topological transition is demonstrated.
A cytoskeletal function for PBRM1 reading methylated microtubules
Authors: Karki Menuka , Jangid Rahul K. , Anish Ramakrishnan , Seervai Riyad N. H. , Bertocchio Jean-Philippe , Hotta Takashi , Msaouel Pavlos , Jung Sung Yun , Grimm Sandra L. , Coarfa Cristian , Weissman Bernard E. , Ohi Ryoma , Verhey Kristen J. , Hodges H. Courtney , Burggren Warren , Dere Ruhee , Park In Young , Prasad B. V. Venkataram , Rathmell W. Kimryn , Walker Cheryl L. , Tripathi Durga N.
Published: April 2021

Methyl marks made by the epigenetic writer SETD2 recruit the epigenetic reader PBRM1 to spindle microtubules during mitosis.
Room temperature coherent control of spin defects in hexagonal boron nitride
Authors: Gottscholl Andreas , Diez Matthias , Soltamov Victor , Kasper Christian , Sperlich Andreas , Kianinia Mehran , Bradac Carlo , Aharonovich Igor , Dyakonov Vladimir
Published: April 2021

Atomic defects in 2D materials show excellent spin coherence time and become promising contenders for quantum applications.
Regulation of macrophage polarization through surface topography design to facilitate implant-to-bone osteointegration
Authors: Zhu Yizhou , Liang Hang , Liu Xiangmei , Wu Jun , Yang Cao , Wong Tak Man , Kwan Kenny Y. H. , Cheung Kenneth M. C. , Wu Shuilin , Yeung Kelvin W. K.
Published: April 2021

Scale-dependent osteo-immune regulation induced by specific TiO
2
nanostructure accelerates implant-to-bone integration.
Rapid expansion of human impact on natural land in South America since 1985
Authors: Zalles Viviana , Hansen Matthew C. , Potapov Peter V. , Parker Diana , Stehman Stephen V. , Pickens Amy H. , Parente Leandro Leal , Ferreira Laerte G. , Song Xiao-Peng , Hernandez-Serna Andres , Kommareddy Indrani
Published: April 2021

A comprehensive record of the land use history of South America reveals that human impact on land increased by 60% since 1985.
X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease
Authors: Günther Sebastian , Reinke Patrick Y. A. , Fernández-García Yaiza , Lieske Julia , Lane Thomas J. , Ginn Helen M. , Koua Faisal H. M. , Ehrt Christiane , Ewert Wiebke , Oberthuer Dominik , Yefanov Oleksandr , Meier Susanne , Lorenzen Kristina , Krichel Boris , Kopicki Janine-Denise , Gelisio Luca , Brehm Wolfgang , Dunkel Ilona , Seychell Brandon , Gieseler Henry , Norton-Baker Brenna , Escudero-Pérez Beatriz , Domaracky Martin , Saouane Sofiane , Tolstikova Alexandra , White Thomas A. , Hänle Anna , Groessler Michael , Fleckenstein Holger , Trost Fabian , Galchenkova Marina , Gevorkov Yaroslav , Li Chufeng , Awel Salah , Peck Ariana , Barthelmess Miriam , Schlünzen Frank , Lourdu Xavier P. , Werner Nadine , Andaleeb Hina , Ullah Najeeb , Falke Sven , Srinivasan Vasundara , França Bruno Alves , Schwinzer Martin , Brognaro Hévila , Rogers Cromarte , Melo Diogo , Zaitseva-Doyle Joanna J. , Knoska Juraj , Peña-Murillo Gisel E. , Mashhour Aida Rahmani , Hennicke Vincent , Fischer Pontus , Hakanpää Johanna , Meyer Jan , Gribbon Philip , Ellinger Bernhard , Kuzikov Maria , Wolf Markus , Beccari Andrea R. , Bourenkov Gleb , von Stetten David , Pompidor Guillaume , Bento Isabel , Panneerselvam Saravanan , Karpics Ivars , Schneider Thomas R. , Garcia-Alai Maria Marta , Niebling Stephan , Günther Christian , Schmidt Christina , Schubert Robin , Han Huijong , Boger Juliane , Monteiro Diana C. F. , Zhang Linlin , Sun Xinyuanyuan , Pletzer-Zelgert Jonathan , Wollenhaupt Jan , Feiler Christian G. , Weiss Manfred S. , Schulz Eike-Christian , Mehrabi Pedram , Karničar Katarina , Usenik Aleksandra , Loboda Jure , Tidow Henning , Chari Ashwin , Hilgenfeld Rolf , Uetrecht Charlotte , Cox Russell , Zaliani Andrea , Beck Tobias , Rarey Matthias , Günther Stephan , Turk Dusan , Hinrichs Winfried , Chapman Henry N. , Pearson Arwen R. , Betzel Christian , Meents Alke
Published: April 2021

A large-scale screen to target SARS-CoV-2

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome is initially expressed as two large polyproteins. Its main protease, M
pro
, is essential to yield functional viral proteins, making it a key drug target. Günther
et al.
used x-ray crystallography to screen more than 5000 compounds that are either approved drugs or drugs in clinical trials. The screen identified 37 compounds that bind to M
pro
. High-resolution structures showed that most compounds bind at the active site but also revealed two allosteric sites where binding of a drug causes conformational changes that affect the active site. In cell-based assays, seven compounds had antiviral activity without toxicity. The most potent, calpeptin, binds covalently in the active site, whereas the second most potent, pelitinib, binds at an allosteric site.

Science
, this issue p.
642
Human plasmacytoid dendritic cells mount a distinct antiviral response to virus-infected cells
Authors: Yun Tae Jin , Igarashi Suzu , Zhao Haoquan , Perez Oriana A. , Pereira Marcus R. , Zorn Emmanuel , Shen Yufeng , Goodrum Felicia , Rahman Adeeb , Sims Peter A. , Farber Donna L. , Reizis Boris
Published: April 2021

pDCs recognize cells infected with human cytomegalovirus and respond with a unique prolonged activation program.
The Rhizosphere Responds: Rich Fen Peat and Root Microbial Ecology after Long-Term Water Table Manipulation
Authors: Rupp Danielle L. , Lamit Louis J. , Techtmann Stephen M. , Kane Evan S. , Lilleskov Erik A. , Turetsky Merritt R.
Published: April 2021

This study demonstrated that roots and the rooting zone in boreal fens support organisms likely capable of methanogenesis, iron cycling, and fungal endophytic association and are directly or indirectly affecting carbon cycling in these ecosystems. These taxa, which react to changes in the water table and associate with roots and, particularly, graminoids, may gain greater biogeochemical influence, as projected higher precipitation rates could lead to an increased abundance of sedges and grasses in boreal fens.
Abdominal cocoon: precipitated by laparoscopic gas insufflation
Authors: Mathew Karingattil George , Akhtar Shakeel , Pius Saajan Ignatius
Published: April 2021

A young male in his early 30s presented to us with increasing swelling at the umbilicus, and an umbilical hernia was diagnosed. At laparoscopic intraperitoneal onlay mesh (IPOM) repair, an unexpected finding of a thin innocuous-looking fibrous film over the small bowel was noted. This finding presented a dilemma as to the probable pathology of this material, and a decision had to be made on whether laparoscopic IPOM could be continued. It was prudently decided to abandon the plan of placing a mesh intraperitoneally and an open repair of the umbilical hernia was done. In retrospect this was a wise decision, as, after 7 months he had to have a laparotomy for intestinal obstruction, when the classic thick fibrous encapsulating abdominal cocoon was seen. Hence here we have followed the evolution of the abdominal cocoon from its original asymptomatic phase to the classic encapsulating sclerosing peritonitis with probably laparoscopic gas insufflation being the precipitating factor.
Autoimmune pulmonary alveolar proteinosis and idiopathic pulmonary haemosiderosis: a dual pathology
Authors: Walsh Laura , McCarthy Cormac , Henry Michael
Published: April 2021

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary condition which leads to excessive accumulation of proteinaceous material within the alveoli. Idiopathic pulmonary haemosiderosis (IPH) is another orphan lung disease and results in recurrent alveolar haemorrhage. This case study describes a case of these two rare pathologies occurring together. A man in his 50s presented with a 6-week history of haemoptysis and worsening dyspnoea. A CT scan of the thorax showed multifocal, bilateral ground glass opacification with a wide differential diagnosis. Full autoantibody screen including myositis panel and coeliac screen were negative. Bronchoscopy with bronchoalveolar lavage and tissue from a transbronchial lung cryobiopsy were non-diagnostic. Tissue from a video-assisted thoracoscopic surgery biopsy confirmed a diagnosis of PAP with IPH as a second separate pathology. The association of IPH and PAP has not previously been described. We discuss these conditions and postulate how and if they may be related.
Cross-sectional study evaluating the association between integrated care and health-related quality of life (HRQOL) in Dutch primary care
Authors: Valentijn Pim P , Kerkhoven Marcel , Heideman Jantien , Arends Rosa
Published: April 2021

Objectives

The aim of this study was to evaluate the association between integrated care and health-related quality of life (HRQOL) in a primary care practice population.

Design

A cross-sectional survey study.

Setting

Primary care practice population.

Participants

A sample (n=5562) of patients in two general practitioner practices in the Netherlands.

Primary outcome measures

The Rainbow Model of Integrated Care Measurement Tool patient version and EQ-5D was used to assess integrated service delivery and HRQOL. The association between integrated care and HRQOL groups was analysed using multivariate logistic regression.

Results

Overall, 933 respondents with a mean age of 62 participated (20% response rate) in this study. The multivariate analysis revealed that positive organisational coordination experiences were linked to better HRQOL (OR=1.87, 95% CI 1.18 to 2.95), and less anxiety and depression problems (OR=0.36, 95% CI 0.20 to 0.63). Unemployment was associated with a poor HRQOL (OR=0.15, 95% CI 0.08 to 0.28). Ageing was associated with more mobility (OR=1.06, 95% CI 1.04 to 1.09), self-care (OR=1.06, 95% CI 1.02 to 1.11), usual activity (OR=1.03, 95% CI 1.01 to 1.05) and pain problems (OR=1.02, 95% CI 1.01 to 1.04). Being married improved the overall HRQOL (OR=1.60, 95% CI 1.13 to 2.26) and decreased anxiety and depression (OR=0.47, 95% CI 0.31 to 0.72). Finally, females had a poor overall HRQOL (OR=1.67, 95% CI 0.48 to 0.93) and more pain and discomfort problems (OR=1.47, 95% CI 1.11 to 1.95).

Conclusion

This study shows for the first time that organisational coordination activities are positively associated with HROQL of adult patients in a primary care context, adding to the evidence of an association between integrated care and HRQOL. Also, unemployment, ageing and being female are accumulating risk factors that should be considered when designing integrated primary care programmes. Further research is needed to explore how various integration types relate to HRQOL for people in local communities.
Study protocol for a multicentre, randomised controlled trial to compare the use of the decellularised dermis allograft in addition to standard care versus standard care alone for the treatment of venous leg ulceration: DAVE trial
Authors: Onida Sarah , Heatley Francine , Peerbux Sarrah , Bolton Layla , Lane Tristan , Epstein David , Gohel Manjit , Poskitt Keith , Cullum Nicky , Norrie John , Lee Robert J , Bradbury Andrew , Dhillon Karen , Chandrasekar Akila , Lomas Richard , Davies A H
Published: April 2021

Introduction

Venous leg ulceration (VLU), the most common type of chronic ulcer, can be difficult to heal and is a major cause of morbidity and reduced quality of life. Although compression bandaging is the principal treatment, it is time-consuming and bandage application requires specific training. There is evidence that intervention on superficial venous incompetence can help ulcer healing and recurrence, but this is not accessible to all patients. Hence, new treatments are required to address these chronic wounds. One possible adjuvant treatment for VLU is human decellularised dermis (DCD), a type of skin graft derived from skin from deceased tissue donors. Although DCD has the potential to promote ulcer healing, there is a paucity of data for its use in patients with VLU.

Methods and analysis

This is a multicentre, parallel group, pragmatic randomised controlled trial. One hundred and ninety-six patients with VLU will be randomly assigned to receive either the DCD allograft in addition to standard care or standard care alone. The primary outcome is the proportion of participants with a healed index ulcer at 12 weeks post-randomisation in each treatment arm. Secondary outcomes include the time to index ulcer healing and the proportion of participants with a healed index ulcer at 12 months. Changes in quality of life scores and cost-effectiveness will also be assessed. All analyses will be carried out on an intention-to-treat (ITT) basis. A mixed-effects, logistic regression on the outcome of the proportion of those with the index ulcer healed at 12 weeks will be performed. Secondary outcomes will be assessed using various statistical models appropriate to the distribution and nature of these outcomes.

Ethics and dissemination

Ethical approval was granted by the Bloomsbury Research Ethics Committee (19/LO/1271). Findings will be published in a peer-reviewed journal and presented at national and international conferences.

Trial registration number

ISRCTN21541209.
Instruments measuring the quality of life among people living with type 2 diabetes mellitus in India: a systematic review protocol
Authors: Demla Chetna , Thomas Anns , Jose Jomol , Joshy Angela L , Hrishikesh M A , Rajendran Ambigai , Parsekar Shradha S
Published: April 2021

Introduction

Type 2 diabetes mellitus affects an individual’s quality of life (QoL); and there are multiple instruments that can be used to measure QoL. The purpose of this systematic review is to identify the existing instruments that have been used to measure QoL in people living with diabetes, and to enlist the major domains (such as physical and psychological components) available in the identified instruments. Additionally, we plan to determine the psychometric properties of the identified QoL instruments using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology.

Methods and analysis

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guideline was followed to report this systematic review protocol. Searches will be conducted on MEDLINE (via PubMed, Web of Science), SCOPUS and CINAHL. Predetermined inclusion/exclusion criteria will be applied to the search results, to include studies with adult individuals diagnosed with type 2 diabetes mellitus, with and without complications, and exclude studies with type 1 diabetes or other clinical illness. Studies conducted outside India will be excluded. Five authors in pairs will independently screen the articles and extract the data that meets the inclusion criteria. The COSMIN criteria will be used to assess the risk of bias of included studies. Narrative synthesis will be performed to analyse the findings of the instruments.

Ethics and dissemination

Ethical permission is not applicable, as this is a systematic review. We intend to disseminate the systematic review findings through a national or international conference and publish the findings in a peer-reviewed journal.

PROSPERO registration number

CRD42020180432.
Loneliness among older adults in the community during COVID-19: a cross-sectional survey in Canada
Authors: Savage Rachel D , Wu Wei , Li Joyce , Lawson Andrea , Bronskill Susan E , Chamberlain Stephanie A , Grieve Jim , Gruneir Andrea , Reppas-Rindlisbacher Christina , Stall Nathan M , Rochon Paula A
Published: April 2021

Objective

Physical distancing and stay-at-home measures implemented to slow transmission of novel coronavirus disease (COVID-19) may intensify feelings of loneliness in older adults, especially those living alone. Our aim was to characterise the extent of loneliness during the first wave in a sample of older adults living in the community and assess characteristics associated with loneliness.

Design

Online cross-sectional survey between 6 May and 19 May 2020.

Setting

Ontario, Canada.

Participants

Convenience sample of members of a national retired educators’ organisation.

Primary outcome measures

Self-reported loneliness, including differences between women and men.

Results

4879 respondents (71.0% women; 67.4% 65–79 years) reported that in the preceding week, 43.1% felt lonely at least some of the time, including 8.3% who felt lonely always or often. Women had increased odds of loneliness compared with men, whether living alone (adjusted OR (aOR) 1.52, 95% CI 1.13 to 2.04) or with others (2.44, 95% CI 2.04 to 2.92). Increasing age group decreased the odds of loneliness (aOR 0.69 (95% CI 0.59 to 0.81) 65–79 years and 0.50 (95% CI 0.39 to 0.65) 80+ years compared with <65 years). Living alone was associated with loneliness, with a greater association in men (aOR 4.26, 95% CI 3.15 to 5.76) than women (aOR 2.65, 95% CI 2.26 to 3.11). Other factors associated with loneliness included: fair or poor health (aOR 1.93, 95% CI 1.54 to 2.41), being a caregiver (aOR 1.18, 95% CI 1.02 to 1.37), receiving care (aOR 1.47, 95% CI 1.19 to 1.81), high concern for the pandemic (aOR 1.55, 95% CI 1.31 to 1.84), not experiencing positive effects of pandemic distancing measures (aOR 1.94, 95% CI 1.62 to 2.32) and changes to daily routine (aOR 2.81, 95% CI 1.96 to 4.03).

Conclusions

While many older adults reported feeling lonely during COVID-19, several characteristics—such as being female and living alone—increased the odds of loneliness. These characteristics may help identify priorities for targeting interventions to reduce loneliness.
Erector spinae plane block for minimally invasive mitral valve surgery: a double-blind, prospective, randomised placebo-controlled trial—a study protocol
Authors: Hoogma Danny Feike , Rex Steffen , Tournoy Jos , Verbrugghe Peter , Fieuws Steffen , Al Tmimi Layth
Published: April 2021

Introduction

In the context of enhanced recovery after cardiac surgery, surgical techniques for mitral valve surgery have witnessed substantial modifications, from approaching the heart using open approaches with traditional sternotomy to thoracoscopic access via minithoracotomy. After cardiac surgery, acute postoperative pain is frequent and caused by surgical incision and retraction. Perioperative analgesia in cardiac surgery still relies mainly on opioids. Although neuraxial techniques could be a valuable non-opioid-based analgesia regimen, they can be associated with devastating complications in situations with (iatrogenic) coagulation abnormalities. Only two randomised clinical trials describe the erector spinae plane (ESP) block to provide sufficient postoperative analgesia following cardiac surgery with median sternotomy. Regarding postoperative analgesia after cardiac surgery with a minithoracotomy approach, adequately designed trials are still lacking. We, therefore, designed a double-blind, placebo-controlled trial to prove the hypothesis that the ESP block reduces opioid consumption in patients undergoing minimally invasive mitral valve surgery (MIMVS).

Methods and analysis

Sixty-four patients undergoing MIMVS will be included in this double-blind, prospective, placebo-controlled trial. Patients will be randomised to receive an ESP block with a catheter with either intermittent ropivacaine 0.5% (ropi group) or normal saline 0.9% (placebo group). Both groups will receive patient-controlled intravenous analgesia with morphine following extubation. Primary endpoint is the 24-hour cumulative morphine consumption after extubation. Multiple secondary endpoints will be evaluated.

Ethics and dissemination

The study is approved by the ethics committee of the University Hospitals Leuven, the Clinical Trials Centre of the University Hospitals Leuven and the ‘Federaal Agentschap voor Geneesmiddelen en Gezondheidsproducten’. Dissemination of the study results will be via scientific papers.

Trial registration number

EudraCT identifier: 2019-001125-27.
Paediatric emergency department dog bite attendance during the COVID-19 pandemic: an audit at a tertiary children’s hospital
Authors: Tulloch John S P , Minford Simon , Pimblett Vicky , Rotheram Matt , Christley Robert M , Westgarth Carri
Published: April 2021

Background

Responses to the COVID-19 pandemic include strict public health measures, such as national lockdowns. During these measures, paediatric emergency department attendances have declined and the prevalence of presenting complaints has changed. This study sought to identify whether dog bite attendance and victim demographics changed during COVID-19 public health measures.

Methods

An audit was conducted of emergency department attendance data from a UK tertiary paediatric hospital between January 2016 and September 2020. Dog bite attendance and victim demographics were explored using χ2 tests and multivariable Poisson regression. The mean monthly percentage of attendance due to dog bites in 2020 was compared against predicted percentages based on previous years’ data.

Results

Dog bite attendance rose in conjunction with the introduction of COVID-19 public health measures and reached a peak in July 2020 (44 dog bites, 1.3% of all attendances were due to dog bites). This was a threefold increase in dog bite attendance. By September 2020, attendance had returned to normal. The demographic profile of child dog bite victims remained the same. Boys had the highest attendance rates in 7–12 year-olds, girls in 4–6 year-olds. Girls showed higher attendance rates in the summer, while boys’ attendance rates were constant throughout the year. COVID-19 public health measures were associated with a 78% increase in attendance for boys and a 66% increase in girls.

Conclusions

COVID-19 national public health measures were associated with an increase in paediatric emergency department dog bite attendance, and may be due to increased child exposure to dogs via ‘stay at home’ orders and school closures. National lockdowns are likely to continue globally throughout the COVID-19 pandemic; this is likely to result in more dog bites. Urgent public health communication and injury prevention strategies are needed to help prevent these avoidable injuries.