bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic effects of missense mutations on SARS-CoV-2 spike glycoprotein stability and receptor-binding affinity
Authors: Teng Shaolei , Sobitan Adebiyi , Rhoades Raina , Liu Dongxiao , Tang Qiyi
Published: August 2020

The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the binding to the permissive cells. The receptor-binding domain (RBD) of SARS-CoV-2 S protein directly interacts with the human angiotensin-converting enzyme 2 (ACE2) on the host cell membrane. In this study, we used computational saturation mutagenesis approaches, including structure-based energy calculations and sequence-based pathogenicity predictions, to quantify the systemic effects of missense mutations on SARS-CoV-2 S protein structure and function. A total of 18 354 mutations in S protein were analyzed, and we discovered that most of these mutations could destabilize the entire S protein and its RBD. Specifically, residues G431 and S514 in SARS-CoV-2 RBD are important for S protein stability. We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein. Moreover, many mutations in N-linked glycosylation sites can increase the stability of the S protein. In addition, we investigated 3705 mutations in SARS-CoV-2 RBD and 11 324 mutations in human ACE2 and found that SARS-CoV-2 neighbor residues G496 and F497 and ACE2 residues D355 and Y41 are critical for the RBD–ACE2 interaction. The findings comprehensively provide potential target sites in the development of drugs and vaccines against COVID-19.
Genomic differentiation in an endemic Philippine genus (Aves:Sarcophanops) owing to geographical isolation on recently disassociated islands
Authors: Campillo Luke C , Manthey Joseph D , Thomson Robert C , Hosner Peter A , Moyle Robert G
Published: August 2020

Phylogeographical studies of Philippine vertebrates have demonstrated that genetic variation is broadly partitioned by Pleistocene island aggregation. Contemporary island discontinuity is expected to influence genetic differentiation but remains relatively undocumented, perhaps because the current episode of island isolation started in relatively recent times. We investigated inter- and intra-island population structure in a Philippine endemic bird genus (Sarcophanops) to determine whether genetic differentiation has evolved during the recent period of isolation. We sequenced thousands of genome-wide restriction site associated DNA (RAD) markers from throughout the Mindanao group to assess fine-scale genetic structure across islands. Specifically, we investigated patterns of gene flow and connectivity within and between taxonomic and geographical bounds. A previous assessment of mitochondrial DNA detected deep structure between Sarcophanops samarensis and a sister species, Sarcophanops steerii, but was insufficient to detect differentiation within either species. Analysis of RAD markers, however, revealed structure within S. samarensis between the islands of Samar/Leyte and Bohol. This genetic differentiation probably demonstrates an effect of recent geographical isolation (after the Last Glacial Maximum) on the genetic structure of Philippine avifauna. We suggest that the general lack of evidence for differentiation between recently isolated populations is a failure to detect subtle population structure owing to past genetic sampling constraints, rather than the absence of such structure.
Photovoice: Integrating Course-Based Research in Undergraduate and Graduate Social Work Education
Authors: Monteblanco Adelle Dora , Moya Eva M
Published: August 2020

Research skills are vital to students’ professional careers and must be cultivated in the social work curriculum. While students and faculty may hesitate to participate in a course-based research project, the authors believe that the Photovoice method is easily adapted to a variety of class and student needs. Photovoice is a field-oriented and qualitative research method that visually documents and communicates community assets and needs. The first purpose of this article is to offer Photovoice as a potential model for instructors to implement a course-based research project. The second purpose is to quantitatively assess changes in students’ reported confidence in social work topics and research activities. Data revealed that the students reported increased confidence in the majority of the content and research evaluated; content examples include economic justice and determinants of social inequalities; research examples include analysing data for patterns and identifying the limitations of research methods. The data illustrate the pedagogical power of Photovoice.
The microglial component of amyotrophic lateral sclerosis
Authors: Clarke Benjamin E , Patani Rickie
Published: August 2020

Microglia are the primary immune cells of the CNS, carrying out key homeostatic roles and undergoing context-dependent and temporally regulated changes in response to injury and neurodegenerative diseases. Microglia have been implicated in playing a role in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by extensive motor neuron loss leading to paralysis and premature death. However, as the pathomechansims of ALS are increasingly recognized to involve a multitude of different cell types, it has been difficult to delineate the specific contribution of microglia to disease. Here, we review the literature of microglial involvement in ALS and discuss the evidence for the neurotoxic and neuroprotective pathways that have been attributed to microglia in this disease. We also discuss accumulating evidence for spatiotemporal regulation of microglial activation in this context. A deeper understanding of the role of microglia in the ‘cellular phase’ of ALS is crucial in the development of mechanistically rationalized therapies.
Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe Coronavirus Disease 2019
Authors: Dofferhoff Anton S M , Piscaer Ianthe , Schurgers Leon J , Visser Margot P J , van den Ouweland Jody M W , de Jong Pim A , Gosens Reinoud , Hackeng Tilman M , van Daal Henny , Lux Petra , Maassen Cecile , Karssemeijer Esther G A , Vermeer Cees , Wouters Emiel F M , Kistemaker Loes E M , Walk Jona , Janssen Rob
Published: August 2020

Background

Respiratory failure and thromboembolism are frequent in severe acute respiratory syndrome coronavirus 2–infected patients. Vitamin K activates both hepatic coagulation factors and extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin K insufficiency, hepatic procoagulant factors are preferentially activated over extrahepatic proteins. Vitamin K also activates matrix Gla protein (MGP), which protects against pulmonary and vascular elastic fiber damage. We hypothesized that vitamin K may be implicated in coronavirus disease 2019 (COVID-19), linking pulmonary and thromboembolic disease.

Methods

A total of 135 hospitalized COVID-19 patients were compared with 184 historic controls. Inactive vitamin K–dependent MGP (desphospho-uncarboxylated [dp-uc] MGP) and prothrombin (PIVKA-II) were measured inversely related to extrahepatic and hepatic vitamin K status, respectively. Desmosine was measured to quantify the rate of elastic fiber degradation. Arterial calcification severity was assessed using computed tomography.

Results

dp-ucMGP was elevated in COVID-19 patients compared with controls (P < .001), with even higher dp-ucMGP in patients with poor outcomes (P < .001). PIVKA-II was normal in 82.1% of patients. dp-ucMGP was correlated with desmosine (P < .001) and with coronary artery (P = .002) and thoracic aortic (P < .001) calcification scores.

Conclusions

dp-ucMGP was severely increased in COVID-19 patients, indicating extrahepatic vitamin K insufficiency, which was related to poor outcome; hepatic procoagulant factor II remained unaffected. These data suggest pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage and thrombosis in severe COVID-19 due to impaired activation of MGP and endothelial protein S, respectively.
Performance of the Bronchoalveolar Lavage FluidAspergillusGalactomannan Lateral Flow Assay With Cube Reader for Diagnosis of Invasive Pulmonary Aspergillosis: A Multicenter Cohort Study
Authors: Jenks Jeffrey D , Prattes Juergen , Frank Johanna , Spiess Birgit , Mehta Sanjay R , Boch Tobias , Buchheidt Dieter , Hoenigl Martin
Published: August 2020

Background

The Aspergillus Galactomannan Lateral Flow Assay (LFA) is a rapid test for the diagnosis of invasive aspergillosis (IA) that has been almost exclusively evaluated in patients with hematologic malignancies. An automated digital cube reader that allows for quantification of results has recently been added to the test kits.

Methods

We performed a retrospective multicenter study on bronchoalveolar lavage fluid (BALF) samples obtained from 296 patients with various underlying diseases (65% without underlying hematological malignancy) who had BALF galactomannan (GM) ordered between 2013 and 2019 at the University of California, San Diego, the Medical University of Graz, Austria, and the Mannheim University Hospital, Germany.

Results

Cases were classified as proven (n = 2), probable (n = 56), putative (n = 30), possible (n = 45), and no IA (n = 162). The LFA showed an area under the curve (AUC) of 0.865 (95% confidence interval [CI] .815–.916) for differentiating proven/probable or putative IA versus no IA, with a sensitivity of 74% and a specificity of 83% at an optical density index cutoff of 1.5. After exclusion of GM as mycological criterion for case classification, diagnostic performance of the LFA was highly similar to GM testing (AUC 0.892 vs 0.893, respectively). LFA performance was consistent across different patient cohorts and centers.

Conclusions

In this multicenter study the LFA assay from BALF demonstrated good diagnostic performance for IA that was consistent across patient cohorts and locations. The LFA may serve a role as a rapid test that may replace conventional GM testing in settings where GM results are not rapidly available.
Coronavirus Disease 2019 Patients in Earlier Stages Exhaled Millions of Severe Acute Respiratory Syndrome Coronavirus 2 Per Hour
Authors: Ma Jianxin , Qi Xiao , Chen Haoxuan , Li Xinyue , Zhang Zheng , Wang Haibin , Sun Lingli , Zhang Lu , Guo Jiazhen , Morawska Lidia , Grinshpun Sergey A , Biswas Pratim , Flagan Richard C , Yao Maosheng
Published: August 2020

Coronavirus disease 2019 (COVID-19) patients exhaled millions of severe acute respiratory syndrome coronavirus 2 RNA copies per hour, which plays an important role in COVID-19 transmission. Exhaled breath had a higher positive rate (26.9%, n = 52) than surface (5.4%, n = 242) and air (3.8%, n = 26) samples.
Viewpoint of a WHO Advisory Group Tasked to Consider Establishing a Closely-monitored Challenge Model of Coronavirus Disease 2019 (COVID-19) in Healthy Volunteers
Authors: Levine Myron M , Abdullah Salim , Arabi Yaseen M , Darko Delese Mimi , Durbin Anna P , Estrada Vicente , Jamrozik Euzebiusz , Kremsner Peter G , Lagos Rosanna , Pitisuttithum Punnee , Plotkin Stanley A , Sauerwein Robert , Shi Sheng-Li , Sommerfelt Halvor , Subbarao Kanta , Treanor John J , Vrati Sudhanshu , King Deborah , Balasingam Shobana , Weller Charlie , Aguilar Anastazia Older , Cassetti M Cristina , Krause Philip R , Restrepo Ana Maria Henao
Published: August 2020

WHO convened an Advisory Group (AG) to consider the feasibility, potential value, and limitations of establishing a closely-monitored challenge model of experimental severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) in healthy adult volunteers. The AG included experts in design, establishment, and performance of challenges. This report summarizes issues that render a COVID-19 model daunting to establish (the potential of SARS-CoV-2 to cause severe/fatal illness, its high transmissibility, and lack of a “rescue treatment” to prevent progression from mild/moderate to severe clinical illness) and it proffers prudent strategies for stepwise model development, challenge virus selection, guidelines for manufacturing challenge doses, and ways to contain SARS-CoV-2 and prevent transmission to household/community contacts. A COVID-19 model could demonstrate protection against virus shedding and/or illness induced by prior SARS-CoV-2 challenge or vaccination. A limitation of the model is that vaccine efficacy in experimentally challenged healthy young adults cannot per se be extrapolated to predict efficacy in elderly/high-risk adults.
Linguistic Diversity in the very Long Run
Authors: John Andrew , Özgür Onur
Published: August 2020

The emergence of language is one of the defining events of the human race. The subsequent development and evolution of languages, over the long sweep of history, reflect political, military, cultural, social and economic forces. The current article offers a highly parsimonious theoretical explanation of the endogenous creation and destruction of distinct languages, focusing purely on the interaction of economic and linguistic forces. Specifically, the article presents an endogenous growth model in which language is an engine of growth: agents who can communicate easily are able to produce and consume more. At the same time, economic interaction among agents affects the evolution of language communities. The resulting strategic complementarities lead agents to form distinct linguistic communities of varying sizes. Larger groups are more productive, so the model generates persistent divergence of output. The model can match a pattern that has been posited as a stylised fact of long-run historical linguistics: a global increase, and subsequent decline, in linguistic diversity. The theory is also broadly consistent with evidence on the size distribution of languages and on the relationship between mobility and linguistic diversity.
Efficacy of multi-electrode linear irreversible electroporation
Authors: Buist Thomas J , Groen Marijn H A , Wittkampf Fred H M , Loh Peter , Doevendans Pieter A F M , van Es René , Elvan Arif
Published: August 2020

Aims

We investigated the efficacy of linear multi-electrode irreversible electroporation (IRE) ablation in a porcine model.

Methods and results

The study was performed in six pigs (weight 60–75 kg). After median sternotomy and opening of the pericardium, a pericardial cradle was formed and filled with blood. A linear seven polar 7-Fr electrode catheter with 2.5 mm electrodes and 2.5 mm inter-electrode spacing was placed in good contact with epicardial tissue. A single IRE application was delivered using 50 J at one site and 100 J at two other sites, in random sequence, using a standard monophasic defibrillator connected to all seven electrodes connected in parallel. The pericardium and thorax were closed and after 3 weeks survival animals were euthanized. A total of 82 histological sections from all 18 electroporation lesions were analysed. A total of seven 50 J and fourteen 100 J epicardial IRE applications were performed. Mean peak voltages at 50 and 100 J were 1079.2 V ± 81.1 and 1609.5 V ± 56.8, with a mean peak current of 15.4 A ± 2.3 and 20.2 A ± 1.7, respectively. Median depth of the 50 and 100 J lesions were 3.2 mm [interquartile range (IQR) 3.1–3.6] and 5.5 mm (IQR 4.6–6.6) (P < 0.001), respectively. Median lesion width of the 50 and 100 J lesions was 3.9 mm (IQR 3.7–4.8) and 5.4 mm (IQR 5.0–6.3), respectively (P < 0.001). Longitudinal sections showed continuous lesions for 100 J applications.

Conclusion

Epicardial multi-electrode linear application of IRE pulses is effective in creating continuous deep lesions.
Medically tailored meals for the management of symptomatic ascites: the SALTYFOOD pilot randomized clinical trial
Authors: Tapper Elliot B , Baki Jad , Nikirk Samantha , Hummel Scott , Asrani Sumeet K , Lok Anna S
Published: August 2020

Background

Ascites is a costly, morbid complication of cirrhosis. Although a low-sodium diet is central to the clinical management of ascites, its efficacy is limited by poor adherence. We aimed to determine the feasibility and impact of low-sodium medically tailored meals (MTM) intervention.

Methods

We enrolled 40 persons with cirrhosis and ascites at the time of a paracentesis in a 12-week, 1:1 randomized trial of standard of care (SOC) (low-sodium diet educational handout) or MTM with <2,000 mg of sodium, >2,100 kcal, and >80 g of protein including a nocturnal protein supplement. We determined the proportion of eligible candidates recruited and adherence to MTM. The primary outcome was the number of paracenteses performed during weeks 0–12. We also collected ascites-specific quality-of-life (ASI-7) scores.

Results

The median age of the enrolled subjects was 54 (IQR, 47–63) years, 46% were female, with median MELD-Na 18 (IQR, 11–23) and albumin 2.7 (IQR, 2.5–3.3) g/dL. At baseline, subjects reported a median of two (IQR, 1–3) paracenteses in the prior 4 weeks. Adherence to the meal schedule was excellent save for when hospitalizations occurred. After 12 weeks, patients in the MTM arm required fewer paracenteses per week than those in the SOC group [median (IQR): 0.34 (0.14–0.54) vs 0.45 (0.25–0.64)]. During the trial, four (20%) SOC patients died, whereas two (10%) died and one (5%) was transplanted in the MTM arm. Ascites-specific quality of life improved to a greater degree in the MTM arm compared to the SOC arm, by 25% (IQR, –11% to 61%) vs 13% (IQR, –28% to 54%).

Conclusion

A trial of MTM for persons with ascites is feasible and potentially effective. Both arms experienced benefits, highlighting the role for improved education and closer monitoring in this challenging condition.
Seismic anisotropy in deforming halite: evidence from the Mahogany salt body
Authors: Prasse Philipp , Wookey James , Kendall J-Michael , Roberts Daniel , Dutko Martin
Published: August 2020

We present unambiguous evidence that the Mahogany salt body, located in the Northern part of the Gulf of Mexico, is seismically anisotropic. Evidence of anisotropy comes from shear wave splitting data obtained from a vertical seismic profile VSP. The data set consists of 48 vertically aligned receivers in a borehole drilled through the salt body. Splitting analysis is performed on shear wave phases that are converted from compressional waves at the top and bottom of the salt body. The phase converted at the top of the salt layer shows a clear signature of seismic anisotropy, while the phase at the base of the salt layer shows negligible splitting. We investigate the possibility of rock salt halite LPO as a cause of the observed anisotropy. A finite element geomechanical salt deformation model of the Mahogany salt body is developed, where deformation history is used as an input to the texture plasticity simulation program VPSC. Assuming a halite salt body, a full elasticity model is then calculated and used to create a synthetic VSP splitting data set. The comparison between the synthetic and real VSP data set shows that LPO of rock salt can explain the observed anisotropy remarkably well. This is the strongest evidence to date of seismic anisotropy in a deforming salt structure. Furthermore, for the first time, we are able to demonstrate clear evidence that deforming halite is the most likely cause of this anisotropy, combining data set analysis and synthetic full wave form modelling based on calculated rock salt elasticities. Neglecting anisotropy in seismic processing in salt settings could lead to potential imaging errors, for example the deformation models show an averaged delta parameter of δ = –0.06, which would lead in a zero offset reflection setting to a depth mismatch of 6.2 per cent. Our work also show how observations of salt anisotropy can be used to probe characteristics of salt deformation.
Effect of centimetric freezing of the near subsurface on Rayleigh and Love wave velocity in ambient seismic noise correlations
Authors: Steinmann René , Hadziioannou Céline , Larose Eric
Published: August 2020

About a decade ago, noise-based monitoring became a key tool in seismology. One of the tools is passive image interferometry (PII), which uses noise correlation functions (NCF) to retrieve seismic velocity variations. Most studies apply PII to vertical components recording oceanic low-frequent ambient noise ( < 1 Hz). In this work, PII is applied to high-frequent urban ambient noise ( > 1 Hz) on three three-component sensors. With environmental sensors inside the subsurface and in the air, we are able to connect observed velocity variations with environmental parameters. Temperatures below 0 °C correlate well with strong shear wave velocity increases. The temperature sensors inside the ground suggest that a frozen layer of less than 5 cm thickness causes apparent velocity increases above 2  % , depending on the channel pair. The observations indicate that the different velocity variation retrieved from the different channel pairs are due to different surface wave responses inherent in the channel pairs. With dispersion curve modelling in a 1-D medium we can verify that surfaces waves of several tens of metres wavelength experience a velocity increase of several percent due to a centimetres thick frozen layer. Moreover, the model verifies that Love waves show larger velocity increases than Rayleigh waves. The findings of this study provide new insights for monitoring with PII. A few days with temperature below 0 °C can already mask other potential targets (e.g. faults or storage sites). Here, we suggest to use vertical components, which is less sensitive to the frozen layer at the surface. If the target is the seasonal freezing, like in permafrost studies, we suggest to use three-component sensors in order to retrieve the Love wave response. This opens the possibility to study other small-scale processes at the shallow subsurface with surface wave responses.
Importance of earthquake rupture geometry on tsunami modelling: the Calabrian Arc subduction interface (Italy) case study
Authors: Tonini Roberto , Basili Roberto , Maesano Francesco Emanuele , Tiberti Mara Monica , Lorito Stefano , Romano Fabrizio , Scala Antonio , Volpe Manuela
Published: August 2020

The behaviour of tsunami waves at any location depends on the local morphology of the coasts, the encountered bathymetric features, and the characteristics of the source. However, the importance of accurately modelling the geometric properties of the causative fault for simulations of seismically induced tsunamis is rarely addressed. In this work, we analyse the effects of using two different geometric models of the subduction interface of the Calabrian Arc (southern Italy, Ionian Sea) onto the simulated tsunamis: a detailed 3-D subduction interface obtained from the interpretation of a dense network of seismic reflection profiles, and a planar interface that roughly approximates the 3-D one. These models can be thought of as representing two end-members of the level of knowledge of fault geometry. We define three hypothetical earthquake ruptures of different magnitudes (Mw 7.5, 8.0, 8.5) on each geometry. The resulting tsunami impact is evaluated at the 50-m isobath in front of coastlines of the central and eastern Mediterranean. Our results show that the source geometry imprint is evident on the tsunami waveforms, as recorded at various distances and positions relative to the source. The absolute differences in maximum and minimum wave amplitudes locally exceed one metre, and the relative differences remain systematically above 20 per cent with peaks over 40 per cent. We also observe that tsunami energy directivity and focusing due to bathymetric waveguides take different paths depending on which fault is used. Although the differences increase with increasing earthquake magnitude, there is no simple rule to anticipate the different effects produced by these end-member models of the earthquake source. Our findings suggest that oversimplified source models may hinder our fundamental understanding of the tsunami impact and great care should be adopted when making simplistic assumptions regarding the appropriateness of the planar fault approximation in tsunami studies. We also remark that the geological and geophysical 3-D fault characterization remains a crucial and unavoidable step in tsunami hazard analyses.
Optimizing treatment cascades for mental healthcare in Mozambique: preliminary effectiveness of the Systems Analysis and Improvement Approach for Mental Health (SAIA-MH)
Authors: Fabian Katrin E , Muanido Alberto , Cumbe Vasco F J , Manaca Nelia , Hicks Leecreesha , Weiner Bryan J , Sherr Kenneth , Wagenaar Bradley H
Published: August 2020

Substantial investments are being made to scale-up access to mental healthcare in low- and middle-income countries, but less attention has been paid to quality and performance of nascent public-sector mental healthcare systems. This study tested the initial effectiveness of an implementation strategy to optimize routine outpatient mental healthcare cascade performance in Mozambique [the Systems Analysis and Improvement Approach for Mental Health (SAIA-MH)]. This study employed a pre–post design from September 2018 to August 2019 across four Ministry of Health clinics among 810 patients and 3234 outpatient mental health visits. Effectiveness outcomes evaluated progression through the care cascade, including: (1) initial diagnosis and medication selection; (2) enrolling in follow-up care; (3) returning after initial consultation within 60 days; (4) returning for follow-up visits on time; (5) returning for follow-up visits adherent to medication and (6) achieving function improvement. Clustered generalized linear models evaluated odds of completing cascade steps pre- vs post-intervention. Facilities prioritized improvements focused on the follow-up cascade, with 62.5% (10 of 16) monthly system modifications targeting medication adherence. At baseline, only 4.2% of patient visits achieved function improvement; during the 6 months of SAIA-MH implementation, this improved to 13.1% of patient visits. Multilevel logistic regression found increased odds of returning on time and adherent [aOR = 1.53, 95% CI (1.21, 1.94), P = 0.0004] and returning on time, adherent and with function improvement [aOR = 3.68, 95% CI (2.57, 5.44), P < 0.0001] after SAIA-MH implementation. No significant differences were observed regarding other cascade steps. The SAIA-MH implementation strategy shows promise for rapidly and significantly improving mental healthcare cascade outcomes, including the ultimate goal of patient function improvement. Given poor baseline mental healthcare cascade performance, there is an urgent need for evidence-based implementation strategies to optimize the performance of mental healthcare cascades in low- and middle-income countries.
Circulation in Insect Wings
Authors: Salcedo Mary K , Socha John J
Published: August 2020

Synopsis

Insect wings are living, flexible structures composed of tubular veins and thin wing membrane. Wing veins can contain hemolymph (insect blood), tracheae, and nerves. Continuous flow of hemolymph within insect wings ensures that sensory hairs, structural elements such as resilin, and other living tissue within the wings remain functional. While it is well known that hemolymph circulates through insect wings, the extent of wing circulation (e.g., whether flow is present in every vein, and whether it is confined to the veins alone) is not well understood, especially for wings with complex wing venation. Over the last 100 years, scientists have developed experimental methods including microscopy, fluorescence, and thermography to observe flow in the wings. Recognizing and evaluating the importance of hemolymph movement in insect wings is critical in evaluating how the wings function both as flight appendages, as active sensors, and as thermoregulatory organs. In this review, we discuss the history of circulation in wings, past and present experimental techniques for measuring hemolymph, and broad implications for the field of hemodynamics in insect wings.
Robotic-assisted thoracoscopic resection and reconstruction of the carina
Authors: Hu Dingzhong , Wang Zhexin , Tantai Jicheng , Yao Feng
Published: August 2020

A 71-year-old man had experienced an irritating cough for 3 months. A diagnosis of squamous cell carcinoma in the carina was made from the bronchoscopic examination. The patient underwent a robotic-assisted resection and reconstruction of the carina. The patient’s postoperative course was uneventful. This is the first description of the feasibility of robotic-assisted carina resection and reconstruction.
Safety and Immunogenicity of the Ad26.RSV.preF Investigational Vaccine Coadministered With an Influenza Vaccine in Older Adults
Authors: Sadoff Jerald , De Paepe Els , Haazen Wouter , Omoruyi Edmund , Bastian Arangassery R , Comeaux Christy , Heijnen Esther , Strout Cynthia , Schuitemaker Hanneke , Callendret Benoit
Published: August 2020

Background

Respiratory syncytial virus (RSV) and influenza cause significant disease burden in older adults. Overlapping RSV and influenza seasonality presents the opportunity to coadminister vaccines for both infections. This study assessed coadministration of the investigational vaccine, Ad26.RSV.preF, an adenovirus serotype 26 (Ad26) vector encoding RSV F protein stabilized in its prefusion conformation (pre-F), with a seasonal influenza vaccine in older adults.

Methods

In this phase 2a, double-blind, placebo-controlled study, 180 adults aged ≥60 years received Ad26.RSV.preF plus Fluarix on day 1 and placebo on day 29, or placebo plus Fluarix on day 1 and Ad26.RSV.preF on day 29 (control).

Results

The coadministration regimen had an acceptable tolerability profile. Reactogenicity was generally higher after Ad26.RSV.preF versus Fluarix, but symptoms were generally transient and mild or moderate. At 28 days after the first vaccination, the upper confidence intervals of the hemagglutination inhibition antibody geometric mean ratio (control/coadministration) for all influenza strains were <2, demonstrating noninferiority. Robust neutralizing and binding antibody responses to RSV A2 were observed in both groups.

Conclusions

Coadministration of Fluarix with Ad26.RSV.preF vaccine had an acceptable safety profile and showed no evidence of interference in immune response. The results are compatible with simultaneous seasonal vaccination with both vaccines.

Clinical Trials Registration

NCT03339713.
Effect of Water, Sanitation, Handwashing, and Nutrition Interventions on Enteropathogens in Children 14 Months Old: A Cluster-Randomized Controlled Trial in Rural Bangladesh
Authors: Grembi Jessica A , Lin Audrie , Karim Md Abdul , Islam Md Ohedul , Miah Rana , Arnold Benjamin F , McQuade Elizabeth T Rogawski , Ali Shahjahan , Rahman Md Ziaur , Hussain Zahir , Shoab Abul K , Famida Syeda L , Hossen Md Saheen , Mutsuddi Palash , Rahman Mahbubur , Unicomb Leanne , Haque Rashidul , Taniuchi Mami , Liu Jie , Platts-Mills James A , Holmes Susan P , Stewart Christine P , Benjamin-Chung Jade , Colford John M , Houpt Eric R , Luby Stephen P
Published: August 2020

Background

We evaluated the impact of low-cost water, sanitation, and handwashing (WSH) and child nutrition interventions on enteropathogen carriage in the WASH Benefits cluster-randomized controlled trial in rural Bangladesh.

Methods

We analyzed 1411 routine fecal samples from children 14 ± 2 months old in the WSH (n = 369), nutrition counseling plus lipid-based nutrient supplement (n = 353), nutrition plus WSH (n = 360), and control (n = 329) arms for 34 enteropathogens using quantitative polymerase chain reaction. Outcomes included the number of co-occurring pathogens; cumulative quantity of 4 stunting-associated pathogens; and prevalence and quantity of individual pathogens. Masked analysis was by intention-to-treat.

Results

Three hundred twenty-six (99.1%) control children had 1 or more enteropathogens detected (mean, 3.8 ± 1.8). Children receiving WSH interventions had lower prevalence and quantity of individual viruses than controls (prevalence difference for norovirus: –11% [95% confidence interval {CI}, –5% to –17%]; sapovirus: –9% [95% CI, –3% to –15%]; and adenovirus 40/41: –9% [95% CI, –2% to –15%]). There was no difference in bacteria, parasites, or cumulative quantity of stunting-associated pathogens between controls and any intervention arm.

Conclusions

WSH interventions were associated with fewer enteric viruses in children aged 14 months. Different strategies are needed to reduce enteric bacteria and parasites at this critical young age.
Human factors engineering for medical devices: European regulation and current issues
Authors: Pelayo Sylvia , Marcilly Romaric , Bellandi Tommaso
Published: August 2020

A large proportion of the patient injuries or deaths attributable to medical device (MD) misuse can be eliminated and/or mitigated by adopting an effective human factors and ergonomics (HFE) approach. The implementation of a usability engineering process is now mandatory for MD manufacturers seeking to obtain the European Union’s CE Mark. Here, we describe the European Union’s HFE regulation and highlight the challenges faced by (i) manufacturers implementing this regulation and (ii) regulatory bodies charged with assessing the compliance of usability files. In Europe, 95% of MD manufacturers are small- and medium-sized enterprises; compliance with the CE Mark regulations is a real challenge to their competitiveness. Levels of knowledge about HFE vary greatly from one regulatory organization to another, which can sometimes lead to very different expectations. We also present the specific use-related risk management approach required by the HFE regulation. Lastly, we focus on the limitations of the HFE regulation for MDs and on future HFE challenges in further reducing and/or eliminating MD use errors. The main challenge is the need to go beyond technology design and the premarket assessment and to look at the postproduction stage; the coupling between an MD and a sociotechnical system can lead to consequences that were not predicted during the design process. This implies the need to consider the emerging properties of technologies in use by involving all the stakeholders.
Risk-adjustment models for clean and colorectal surgery surgical site infection for the Spanish health system
Authors: Angel García Daniel , Martínez Nicolás Ismael , García Marín José Andrés , Soria Aledo Victoriano
Published: August 2020

Objective

To develop risk-adjusted models for two quality indicators addressing surgical site infection (SSI) in clean and colorectal surgery, to be used for benchmarking and quality improvement in the Spanish National Health System.

Study design

A literature review was undertaken to identify candidate adjustment variables. The candidate variables were revised by clinical experts to confirm their clinical relevance to SSI; experts also offered additional candidate variables that were not identified in the literature review. Two risk-adjustment models were developed using multiple logistic regression thus allowing calculation of the adjusted indicator rates.

Data source

The two SSI indicators, with their corresponding risk-adjustment models, were calculated from administrative databases obtained from nine public hospitals. A dataset was obtained from a 10-year period (2006–2015), and it included data from 21 571 clean surgery patients and 6325 colorectal surgery patients.

Analysis methods

Risk-adjustment regression models were constructed using Spanish National Health System data. Models were analysed so as to prevent overfitting, then tested for calibration and discrimination and finally bootstrapped.

Results

Ten adjustment variables were identified for clean surgery SSI, and 23 for colorectal surgery SSI. The final adjustment models showed fair calibration (Hosmer–Lemeshow: clean surgery χ2 = 6.56, P = 0.58; colorectal surgery χ2 = 6.69, P = 0.57) and discrimination (area under receiver operating characteristic [ROC] curve: clean surgery 0.72, 95% confidence interval [CI] 0.67–0.77; colorectal surgery 0.62, 95% CI 0.60–0.65).

Conclusions

The proposed risk-adjustment models can be used to explain patient-based differences among healthcare providers. They can be used to adjust the two proposed SSI indicators.
Effect of a novel animal milk oligosaccharide biosimilar on the gut microbial communities and metabolites of in vitro incubations using feline and canine fecal inocula
Authors: Oba Patrícia M , Vidal Sara , Wyss Romain , Miao Yong , Adesokan Yemi , Swanson Kelly S
Published: August 2020

Milk oligosaccharides (MO) confer multiple potential physiological benefits, such as the selective growth promotion of beneficial microbiota, inhibition of enteric pathogen growth and adhesion to enterocytes, maturation of the gut mucosal barrier, and modulation of the gastrointestinal immune system. This study was conducted to determine the fermentation potential of GNU100, an animal MO biosimilar, in an in vitro system using healthy canine and feline fecal inocula. Single feline and single canine fecal samples were used to inoculate a batch fermentation system. Tubes containing a blank control (BNC), GNU100 at 0.5% (5 g/L; GNU1), or GNU100 at 1.0% (10 g/L; GNU2) were incubated for 48 h. Gas pressure, pH, lactate, short-chain fatty acids (SCFA; acetate, propionate, and butyrate), and branched-chain fatty acids (BCFA; isobutyrate, isovalerate, and valerate) were measured after 6, 24, and 48 h. Ammonium and microbiota (total bacteria by flow cytometry and Pet-16Seq; Lactobacillus and Bifidobacterium by quantitative polymerase chain reaction ) were measured after 24 and 48 h. Data were analyzed using the Mixed Models procedure of SAS. Substrates were considered to be a fixed effect and replicates considered to be a random effect. Tukey’s multiple comparison analysis was used to compare least squares means, with differences considered significant with P < 0.05. In feline and canine incubations, SCFA increases were greater (P < 0.0001) in GNU100 compared with BNC, with acetate making up the largest SCFA proportion (P < 0.0001). GNU100 cultures led to greater increases (P < 0.0001) in lactate and ammonium than BNC in the feline incubations. GNU100 cultures led to greater increases (P < 0.0001) in ammonium than BNC in canine incubations and greater increases (P < 0.0001) in BCFA than BNC in feline incubations. Pet-16Seq microbial profiles from the feline and canine fecal incubations exhibited a modulation after GNU100 fermentation, with a reduction of the genera Escherichia/Shigella and Salmonella. In feline incubations, Bifidobacterium populations had greater increases (P < 0.0001) in GNU100 than BNC. In feline incubations, Lactobacillus populations had greater increases (P = 0.01) in GNU100 than BNC, with GNU1 leading to greater increases (P = 0.02) in Lactobacillus than BNC tubes in canine incubations. Overall, this study demonstrated that GNU100 was fermented in an in vitro fermentation system inoculated with canine and feline microbiota, resulting in the growth of beneficial bacteria and the production of SCFA, BCFA, and ammonium.
Characterizing the amount and variability of intramuscular fat deposition throughout pork loins using barrows and gilts from two sire lines
Authors: Redifer Jack D , Beever Jon E , Stahl Chad A , Boler Dustin D , Dilger Anna C
Published: August 2020

The objective was to determine the amount and variability of intramuscular fat (IMF) in a pork loin attributable to anatomical chop location, sex, and sire line. Pigs were sired by commercially available terminal Duroc boars selected for meat quality (MQ; n = 96) or lean growth (LG; n = 96) and equally split between barrows and gilts. After slaughter and fabrication, bone-in chops were removed from four locations of each left-side loin (A = 6th rib, B = 10th rib, C = last rib, and D = 4th lumbar vertebrae). An adjacent pair of chops from each location was collected and evaluated for visual color and marbling, subjective firmness, moisture and extractable lipid (IMF) (anterior chop), and Warner–Bratzler shear force (posterior chop). Data were analyzed using the MIXED procedure of SAS as a split-plot design. Homogeneity of variances was tested on raw data using Levene’s test of the GLM procedure and found to be heterogeneous. Thus, a two-variance model was fit using the REPEATED statement of the MIXED procedure, grouped by pig. The mivque(0) option of the VARCOMP procedure was used to calculate the proportion of variability that each factor contributed to the total variance. Barrows (3.64%) produced chops with greater (P < 0.01) IMF content than gilts (3.20%), and barrows (2.14) had greater (P < 0.01) IMF variability than gilts (1.23). Chops from MQ pigs (4.02%) exhibited greater (P < 0.01) IMF content than LG (2.82%), and MQ (1.76) had greater IMF variability (P < 0.01) than LG pigs (0.97). Chops from locations A (3.80%) and D (3.77%) had greater IMF than B (3.34%; P < 0.01), and A, B, and D had greater IMF than C (2.77%; P < 0.01). Variances of IMF also differed (A = 1.44, B = 1.59, C = 1.05, and D = 2.18; P = 0.01) across chop locations. Of the variability in IMF, 33.0% was attributed to sire line, 10.16% to chop location, and 4.01% to sex, with 52.83% not accounted for by these three factors. Location A chops were the most (P < 0.01) tender (2.57 kg) and C chops the least (P < 0.01) tender (2.93 kg), while B and D chops were intermediate and not different from each other. No differences in variability (P = 0.40) of tenderness were observed among chop locations (A = 0.31, kg B = 0.24 kg, C = 0.24 kg, and D = 0.23 kg). These results demonstrated that variability in tenderness values did not reflect the variability of IMF. In conclusion, chop location, sex, and sire line all contribute to the amount and variability of pork loin marbling.
Relative bioavailability of guanidinoacetic acid delivered ruminally or abomasally to cattle
Authors: Speer Hannah F , Pearl Kimberly A , Titgemeyer Evan C
Published: August 2020

This study assessed the relative bioavailability of guanidinoacetic acid (GAA) in cattle. Seven ruminally cannulated Holstein steers (initial body weight of 280 kg) were used in an experiment with a 5 × 5 Latin square design; the two additional steers received a treatment sequence identical to two steers in the Latin square. Treatments were: control (no GAA, water infusion), ruminal infusion of 10 or 20 g/d GAA, and abomasal infusion of 10 or 20 g/d GAA, with all infusions delivered continuously. Periods were 7 d in length, and on day 7, blood and urine samples were collected to determine the concentrations of GAA and its associated metabolites. Plasma creatine concentrations increased linearly (P < 0.01) with GAA infusion to the abomasum and tended to increase linearly (P = 0.06) when GAA was infused ruminally. Urinary creatine concentrations increased linearly with increasing amounts of GAA infused in the abomasum (P < 0.01) and the rumen (P < 0.05). There were no significant effects of GAA infusion to either the abomasum or rumen on plasma or urinary concentrations of GAA. Plasma creatinine concentrations were not affected by GAA infusion to the abomasum or rumen. Urinary creatinine concentrations decreased when GAA was infused abomasally (P < 0.05). Because plasma and urinary creatine concentrations yielded the statistically strongest linear responses, they were selected as the primary response criteria for quantifying ruminal escape of GAA. Calculated by slope-ratio methodology, estimates for the ruminal escape of GAA based on plasma creatine and urinary creatine concentrations were 47% and 49%, respectively. Ruminally infused GAA was about half as effective as abomasally infused GAA in elevating plasma and urinary concentrations of creatine.
Comparison of in Vitro and in Planta Toxicity of Vip3A for Lepidopteran Herbivores
Authors: Khan Muhammad Hassaan , Jander Georg , Mukhtar Zahid , Arshad Muhammad , Sarwar Muhammad , Asad Shaheen
Published: August 2020

Agricultural pest infestation is as old as domestication of food crops and contributes a major share to the cost of crop production. In a transgenic pest control approach, plant production of Vip3A, an insecticidal protein from Bacillus thuringiensis, is effective against lepidopteran pests. A synthetic Vip3A gene was evaluated for efficacy against Spodoptera litura Fabricius (Lepidoptera: Noctuidae; cotton leafworm), Spodoptera exigua Hübner (Lepidoptera: Noctuidae; beet armyworm), Spodoptera frugiperda Smith (Lepidoptera: Noctuidae; fall armyworm), Helicoverpa armigera Hübner (Lepidoptera: Noctuidae; cotton bollworm), Helicoverpa zea Boddie (Lepidoptera: Noctuidae; corn earworm), Heliothis virescens Fabricius (Lepidoptera: Noctuidae; tobacco budworm), and Manduca sexta L. (Lepidoptera: Sphingidae; tobacco hornworm) in tobacco. In artificial diet assays, the concentration required to achieve 50% mortality was highest for H. zea followed by H. virescens > S. exigua > H. armigera > M. sexta > S. frugiperda > S. litura. By contrast, in bioassays with detached leaves from Vip3A transgenic tobacco, the time until 50% lethality was M. sexta > H. virescens > S. litura > H. zea > H. armigera > S. exigua. There was no significant correlation between the artificial diet and transgenic plant bioassay results. Notably, the two insect species that are best-adapted for growth on tobacco, M. sexta and H. virescens, showed the greatest time to 50% mortality on Vip3A-transgenic tobacco. Together, our results suggest that artificial diet assays may be a poor predictor of Vip3A efficacy in transgenic plants, lepidopteran species vary in their sensitivity to Vip3A in diet-dependent manner, and host plant adaptation of the targeted herbivores should be considered when designing transgenic plants for pest control.
Inheritance and Fitness Costs of Cry3Bb1 Resistance in Diapausing Field Strains of Western Corn Rootworm (Coleoptera: Chrysomelidae)
Authors: Shrestha Ram B , Gassmann Aaron J
Published: August 2020

Field-evolved resistance to Cry3Bb1 corn by western corn rootworm, Diabrotica virgifera virgifera LeConte (Colleoptera: Chrysomellidae), has been reported in field populations in Iowa, Illinois, Nebraska, and Minnesota. Inheritance and fitness costs associated with Cry3Bb1 resistance have been determined for non-diapausing laboratory strains of western corn rootworm with either laboratory-selected resistance or field-derived resistance. However, information on inheritance and fitness costs of Cry3Bb1 resistance in the diapausing field populations is lacking. In this study, we determined the inheritance of Cry3Bb1 resistance for four diapausing field strains of western corn rootworm using plant-based bioassays. We also determined the fitness costs for eight diapausing field populations in a greenhouse experiment. We found that Cry3Bb1 resistance was an autosomal trait and that the inheritance of resistance was mostly non-recessive; however, there was some variation in the dominance of Cry3Bb1 resistance. We did not find evidence of fitness costs affecting survival to adulthood, developmental rate, or adult dry mass. However, we did detect a fitness cost affecting adult size. The results of this study will add to the current understanding of field-evolved resistance to Cry3Bb1 corn by western corn rootworm and help in developing better strategies to manage resistance.