bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences among families in craniofacial shape at early life-stages of Arctic charr (Salvelinus alpinus)
Authors: Beck Samantha V. , Räsänen Katja , Leblanc Camille A. , Skúlason Skúli , Jónsson Zophonías O. , Kristjánsson Bjarni K.
Published: October 2020

Background

Organismal fitness can be determined at early life-stages, but phenotypic variation at early life-stages is rarely considered in studies on evolutionary diversification. The trophic apparatus has been shown to contribute to sympatric resource-mediated divergence in several taxa. However, processes underlying diversification in trophic traits are poorly understood. Using phenotypically variable Icelandic Arctic charr (Salvelinus alpinus), we reared offspring from multiple families under standardized laboratory conditions and tested to what extent family (i.e. direct genetic and maternal effects) contributes to offspring morphology at hatching (H) and first feeding (FF). To understand the underlying mechanisms behind early life-stage variation in morphology, we examined how craniofacial shape varied according to family, offspring size, egg size and candidate gene expression.

Results

Craniofacial shape (i.e. the Meckel’s cartilage and hyoid arch) was more variable between families than within families both across and within developmental stages. Differences in craniofacial morphology between developmental stages correlated with offspring size, whilst within developmental stages only shape at FF correlated with offspring size, as well as female mean egg size. Larger offspring and offspring from females with larger eggs consistently had a wider hyoid arch and contracted Meckel’s cartilage in comparison to smaller offspring.

Conclusions

This study provides evidence for family-level variation in early life-stage trophic morphology, indicating the potential for parental effects to facilitate resource polymorphism.
Correction to: Alternative graphical displays for the monitoring of epidemic outbreaks, with application to COVID-19 mortality
Authors: Perneger Thomas , Kevorkian Antoine , Grenet Thierry , Gallée Hubert , Gayet-Ageron Angèle
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Preventing mother to child transmission of HIV: lessons learned from China
Authors: Dong Yu , Guo Wei , Gui Xien , Liu Yanbin , Yan Yajun , Feng Ling , Liang Ke
Published: October 2020

Background

The program for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) was launched in 2003 in China, but few studies have been conducted to describe the panorama of PMTCT. We investigated the rate and associated factors of mother-to-child transmission (MTCT) in China from 2004 to 2018.

Methods

HIV-infected pregnant women from two areas in China between 2004 and 2018 were enrolled. Antiretrovirals (ARVs) were provided to the mothers and their babies, and the children were followed and tested for HIV.

Results

In total, 857 mothers and their 899 children were enrolled, and the overall MTCT rate was 6.6% (95% CI 5.0–8.2). The MTCT rates of nonintervention, only formula feeding (FF), infant prophylaxis (IP) + FF, single dosage antiretrovirals (sdARVs) + IP + FF, zidovudine (AZT) alone+IP + FF and prenatal combination antiretroviral therapy (cART) + IP + FF were 36.4, 9.4, 10.0, 5.7, 3.8 and 0.3%, respectively. The MTCT rate declined over time. No ARVs, CD4 count < 200/μL, low birth weight, and breastfeeding were associated with MTCT of HIV. For different ARVs, a higher MTCT rate was observed for AZT alone, sdARVs, and no ARVs compared to cART for pregnant women.

Conclusions

Although the overall MTCT rate remains relatively high, the real-world effect of prenatal cART+IP + FF in China has exerted the same protective effects in high-income countries. With the extension of prenatal cART for pregnant women with HIV, the MTCT rate of HIV has gradually declined in China. However, the coverage of prenatal cART for pregnant women should be further improved. The effect of only post-exposure prophylaxis for infants was limited.
Retraction of transporting bone segment during Ilizarov bone transport
Authors: Ma Yunhong , Yin Qudong , Wu Yongwei , Wang Zongnan , Sun Zhenzhong , Gu Sanjun , Rui Yongjun , Han Xiaofei
Published: October 2020

Background

Retraction of transporting bone segment (TBS) may occur when the fixator of the TBS is removed prior to full consolidation of the distracted callus, which has adverse effect on the healing of the docking site. However, there are few reports on the retraction of TBS. The purpose of this study is to analyze the causes and risk factors of the retraction of TBS.

Methods

The clinical data of 37 cases with tibial bone defect treated by Ilizarov bone transport were analyzed retrospectively, in whom the TBS fixator was removed prior to full consolidation of the distracted callus and union of the docking site. Bivariate correlation was used to analyze relationship between the retraction distance of TBS and potential risk factors including age, gender, course, length of bone defect, number of operations, size of TBS, transport distance, timing and time interval of removal of TBS fixator. Risk factors with significant level were further identified using multivariate linear regression.

Results

Bivariate correlation showed that the timing of removal was negatively correlated with the retraction distance, and the time interval and transport distance were positively correlated with the retraction distance(p < 0.05), the age, gender, course, length of bone defect, size of TBS and number of operations were not correlated with the retraction distance(p > 0.05). Multivariate linear regression of the 3 risk factors showed that the timing of removal and time interval were the main risk factors affecting the retraction distance (p < 0.05), but the transport distance was not (p > 0.05).

Conclusion

The traction forces of TBS endured from the soft tissues and the unconsolidated distracted callus have elastic properties, which can make retraction of TBS. The timing of removal and time interval are the main risk factors of the retraction of TBS. In the case of early removal, another external fixation or quickly converted to internal fixation should be performed to avoid the adverse effect of more retraction.
Horizontal inequity in the use and access to health care in Uruguay
Authors: González Cecilia , Triunfo Patricia
Published: October 2020

Background

In 2007 Uruguay began a reform in the health sector towards the construction of a National Integrated Health System (SNIS), based on public insurance with private and public provision. The main objective of the reform was to universalize access to health services.

Methods

Data comes from the first National Health Survey conducted in 2014 and available since 2016. Concentration indices are calculated for different indicators of use and access to medical services, for the population 18 years of age and older, and for different subgroups (age, sex, region and type of coverage). The indices are decomposed into need and non-need variables and the contribution of each of them to total inequality is analyzed. Horizontal inequity is calculated.

Results

Results show pro-rich inequality for medical consultations, medical analysis, medication use and non-access due to costs. Type of health coverage is the variable that explains most of the inequality: private coverage is pro-rich while public coverage is pro-poor. Income does not appear as significant to explain inequality, except for access issues.

From the population subgroups’ analysis, there is no evidence of inequality for the group of 60 years old or more. On the other hand, studies such as Pap Smear and prostate, which may be associated with preventive studies,, shows pro-rich inequality and, in both cases, the main contribution is given by income.

Conclusions

The analysis of health inequity shows pro-rich inequity in medical consultations, medical analysis, medication use and lack of access due to costs. The type of health coverage explains these inequalities; in particular, private coverage is pro-rich. These results suggest that the type of health coverage are capturing the income factor, since higher income individuals will be more likely to be treated in the private system.
Treatment monitoring of colorectal cancer by integrated analysis of plasma concentration and sequencing of circulating tumor DNA
Authors: Yeh Yu-Min , Lin Peng-Chan , Lee Chung-Ta , Chen Shang-Hung , Lin Bo-Wen , Lin Shao-Chieh , Chen Po-Chuan , Chan Ren-Hao , Shen Meng-Ru
Published: October 2020

Circulating cell-free DNA (cfDNA) analysis is an important tool for cancer monitoring. The patient-specific mutations identified in colorectal cancer (CRC) tissues are usually used to design the cfDNA analysis. Despite high specificity in predicting relapse, the sensitivity in most studies is around 40–50%. To improve this weakness, we designed a cfDNA panel according to the CRC genomic landscape and recurrent-specific mutations. The pathological variants in cfDNA samples from 60 CRC patients were studied by a next-generation sequencing (NGS) method incorporating the dual molecular barcode. Interestingly, patients in the disease positive group had a significantly higher cfDNA concentration than those in the disease negative group. Based on receiver operating characteristic analysis, the cfDNA concentration of 7 ng/mL was selected into the analytical workflow. The sensitivity in determining the disease status was 72.4%, which represented a considerable improvement on prior studies, and the specificity remained high at 80.6%. Compared to standard imaging and laboratory studies, earlier detection of residual disease and clinical benefits were shown on two cases by this cfDNA assay. We conclude this integrative framework of cfDNA analytical pipeline with a satisfactory sensitivity and specificity could be used in postoperative CRC surveillance.
Correction to: Alcohol consumption and its associated factors among pregnant women in Sub-Saharan Africa: A systematic review and meta-analysis
Authors: Addila Alemu Earsido , Bisetegn Telake Azale , Gete Yigzaw Kebede , Mengistu Mezgebu Yitayal , Beyene Getnet Mihretie
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Correction to: Xanthohumol microbiome and signature in healthy adults (the XMaS trial): a phase I triple-masked, placebo-controlled clinical trial
Authors: Bradley Ryan , Langley Blake O. , Ryan Jennifer J. , Phipps John , Hanes Douglas A. , Stack Emily , Jansson Janet K. , Metz Thomas O. , Stevens Jan Frederik
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Best practices for variant calling in clinical sequencing
Authors: Koboldt Daniel C.
Published: October 2020

Next-generation sequencing technologies have enabled a dramatic expansion of clinical genetic testing both for inherited conditions and diseases such as cancer. Accurate variant calling in NGS data is a critical step upon which virtually all downstream analysis and interpretation processes rely. Just as NGS technologies have evolved considerably over the past 10 years, so too have the software tools and approaches for detecting sequence variants in clinical samples. In this review, I discuss the current best practices for variant calling in clinical sequencing studies, with a particular emphasis on trio sequencing for inherited disorders and somatic mutation detection in cancer patients. I describe the relative strengths and weaknesses of panel, exome, and whole-genome sequencing for variant detection. Recommended tools and strategies for calling variants of different classes are also provided, along with guidance on variant review, validation, and benchmarking to ensure optimal performance. Although NGS technologies are continually evolving, and new capabilities (such as long-read single-molecule sequencing) are emerging, the “best practice” principles in this review should be relevant to clinical variant calling in the long term.
miR-137 boosts the neuroprotective effect of endothelial progenitor cell-derived exosomes in oxyhemoglobin-treated SH-SY5Y cells partially via COX2/PGE2 pathway
Authors: Li Yuchen , Wang Jinju , Chen Shuzhen , Wu Pei , Xu Shancai , Wang Chunlei , Shi Huaizhang , Bihl Ji
Published: October 2020

Background

We have previously verified the beneficial effects of exosomes from endothelial progenitor cells (EPC-EXs) in ischemic stroke. However, the effects of EPC-EXs in hemorrhagic stroke have not been investigated. Additionally, miR-137 is reported to regulate ferroptosis and to be involved in the neuroprotection against ischemic stroke. Hence, the present work explored the effects of miR-137-overexpressing EPC-EXs on apoptosis, mitochondrial dysfunction, and ferroptosis in oxyhemoglobin (oxyHb)-injured SH-SY5Y cells.

Methods

The lentiviral miR-137 was transfected into EPCs and then the EPC-EXs were collected. RT-PCR was used to detect the miR-137 level in EPCs, EXs, and neurons. The uptake mechanisms of EPC-EXs in SH-SY5Y cells were explored by the co-incubation of Dynasore, Pitstop 2, Ly294002, and Genistein. After the transfection of different types of EPC-EXs, flow cytometry and expression of cytochrome c and cleaved caspase-3 were used to detect the apoptosis of oxyHb-injured neurons. Neuronal mitochondrial function was assessed by reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) depolarization, and cellular ATP content. Cell ferroptosis was measured by lipid peroxidation, iron overload, degradation of glutathione, and glutathione peroxidase 4. Additionally, recombinational PGE2 was used to detect if activation of COX2/PGE2 pathway could reverse the protection of miR-137 overexpression.

Results

The present work showed (1) EPC-EXs could be taken in by SH-SY5Y cells via caveolin-/clathrin-mediated pathways and macropinocytosis; (2) miR-137 was decreased in neurons after oxyHb treatment, and EXsmiR-137 could restore the miR-137 levels; (3) EXsmiR-137 worked better than EXs in reducing the number of apoptotic neurons and pro-apoptotic protein expression after oxyHb treatment; (4) EXsmiR-137 are more effective in improving the cellular MMP, ROS, and ATP level; (5) EXsmiR-137, but not EXs, protected oxyHb-treated SH-SY5Y cells against lipid peroxidation, iron overload, degradation of glutathione, and glutathione peroxidase 4; and (6) EXsmiR-137 suppressed the expression of the COX2/PGE2 pathway, and activation of the pathway could partially reverse the neuroprotective effects of EXsmiR-137.

Conclusion

miR-137 overexpression boosts the neuroprotective effects of EPC-EXs against apoptosis and mitochondrial dysfunction in oxyHb-treated SH-SY5Y cells. Furthermore, EXsmiR-137 rather than EXs can restore the decrease in miR-137 levels and inhibit ferroptosis, and the protection mechanism might involve the miR-137-COX2/PGE2 signaling pathway.
Correction to: Is diet partly responsible for differences in COVID-19 death rates between and within countries?
Authors:   The ARIA group, Bousquet Jean , Anto Josep M. , Iaccarino Guido , Czarlewski Wienczyslawa , Haahtela Tari , Anto Aram , Akdis Cezmi A. , Blain Hubert , Walter Canonica G. , Cardona Victoria , Cruz Alvaro A. , Illario Maddalena , Ivancevich Juan Carlos , Jutel Marek , Klimek Ludger , Kuna Piotr , Laune Daniel , Larenas‑Linnemann Désirée , Mullol Joaquim , Papadopoulos Nikos G. , Pfaar Oliver , Samolinski Boleslaw , Valiulis Arunas , Yorgancioglu Arzu , Zuberbier Torsten
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Interferometric redatuming by deconvolution and correlation-based focusing
Authors: Barrera Diego F. , Schleicher Joerg , Brackenhoff Joeri
Published: October 2020

Seismic interferometry is a method used to calculate wavefields for sources and receivers that are located where only sources or only receivers are available. There are correlation- or deconvolution-based interferometric methods that can be used to reposition the seismic array from the earth’s surface to an arbitrary datum at depth. Based on the one-way reciprocity theorems of convolution and correlation type, we have determined that interferometric redatuming can be achieved in a deconvolution-only procedure in three steps. The first two steps consist of separately retrieving, for sources at the earth’s surface, the downward- and upward-propagating Green’s functions at receivers at the datum, which are then used in the third step to reposition the sources to the datum. For the involved deconvolutions, transmitted and backscattered wavefields need to be modeled with a velocity model between the acquisition and datum levels. Our numerical experiments demonstrate that the method can help to reduce nonphysical events and other artifacts that commonly arise in purely correlation-based procedures. If a high-quality overburden-velocity model is available, it correctly accounts for inhomogeneities in the overburden medium. Because the method’s sensitivity to the velocity model is mainly introduced by backscattering at overburden heterogeneities, a smooth model is sufficient when overburden scattering is weak.
An approximate inversion scheme for surface-borehole electromagnetic in the presence of steel casing: 1D implementation
Authors: Cuevas Nestor H.
Published: October 2020

I have developed an approximate inversion scheme for surface-borehole electromagnetic data. The method aims at reducing the computational burden arising by the fine discretization required to accurately solve for the field distribution in the full complexity of the borehole system together with the reservoir medium. I first analyze numerical simulations of the surface-borehole response performed for a 1D layered earth, also incorporating the realistic complexity of the borehole system. The analysis brings useful insight to the requirement of incorporating fluid and mud/cement electrical properties when implementing an inversion by numerically simulating the full complexity of the system. Subsequently, the synthetic data set was used to test an inversion method that uses the data dominated by the casing effect to approximately describe the casing secondary fields. A scaling factor is then introduced to account for the current induced in the well as the exciting source is placed further below the casing shoe. The method is found to fairly well recover the known 1D resistivity strata; still, some bias is expected for the resistivity close below the casing shoe, where the data are anticipated to be the most distorted by the casing effect.
VP and VS prediction from digital rock images using a combination of U-Net and convolutional neural networks
Authors: Cui Rongang , Cao Danping , Liu Qiang , Zhu Zhaolin , Jia Yan
Published: October 2020

Predicting elastic parameters based on digital rock images is an interesting application of a convolutional neural network (CNN), which can improve the efficiency of prediction. Predicting elastic parameters by a conventional CNN, which is used for image classification such as LeNet and AlexNet, lacks geophysical constraints, and its accuracy in predicting elastic parameters is poor, with limited training data available. The combination of a U-Net and a convolutional neural network (CUCNN) is proposed to predict the elastic parameters from digital rock images with limited training data. In CUCNN, the rock matrix and pore types segmented from gray-scale images are treated as constraints that induce the convolutional kernels to extract the global as well as the local-scale rock features. The loss function, designed in a composite form to accelerate the convergence speed, contains the segmentation error and elastic parameters predicted from the gray-scale images. By adding geophysical constraints to the CNN, an implicit representation from the gray-scale image to the elastic parameters can be gained, which can improve the accuracy and efficiency of parameter prediction. Our method was tested using training and verification data derived from 1800 2D image slices of Berea sandstone samples, and the results were compared against the CNN model. The [Formula: see text] and [Formula: see text] were calculated by the finite-element method as the control to test the performance of both models. Our results show that CUCNN’s R2 score is 0.84, which increased by as much as 0.21 compared to the conventional CNN.
Cardiovascular risk in patients with severe mental illness in Italy
Authors: Salvi Virginio , Aguglia Andrea , Barone-Adesi Francesco , Bianchi Davide , Donfrancesco Chiara , Dragogna Filippo , Palmieri Luigi , Serafini Gianluca , Amore Mario , Mencacci Claudio
Published: October 2020

Background

Patients with severe mental illness (SMI), such as schizophrenia or bipolar disorders, are more frequently affected by metabolic syndrome and cardiovascular (CV) diseases than the general population, with a significant reduction in life expectancy. Beyond metabolic syndrome, quantifying the risk of CV morbidity in the long-term may help clinicians to put in place preventive strategies. In this study, we assessed 10-year CV risk in patients with SMI and healthy individuals using an algorithm validated on the Italian general population.

Methods

Patients aged 35–69 years diagnosed with SMI were consecutively recruited from psychiatric acute care units. Single CV risk factors were assessed, and 10-year CV risk calculated by means of the CUORE Project 10-year CV risk algorithm, based on the combination of the following risk factors: age, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking habit, and hypertensive treatment. Patients’ data were compared with those from the general population. The 10-year CV risk was log-transformed, and multivariable linear regression was used to estimate mean ratios, adjusting for age, and education.

Results

Three hundred patients and 3,052 controls were included in the analysis. Among men, the 10-year CV risk score was very similar between patients with SMI and the general population (mean ratio [MR]: 1.02; 95%CI 0.77–1.37), whereas a 39% increase in 10-year CV risk was observed in women with SMI compared to the general population (MR: 1.39; 95%CI 1.16–1.66).

Conclusions

In our study, women with SMI were consistently more at risk than the general population counterpart, even at younger age.
Conflicted Representations: Language, Lexicography, and Johnson’s “Langscape” of War
Authors: Mugglestone Lynda
Published: October 2020

Books, as Samuel Johnson stated in 1754 in his Dictionary of the English Language neared completion, always exert “a secret influence on the understanding” so that the reader is informed in both overt and covert ways. Reference works, he stressed, were no exception. As this essay explores, Johnson’s precepts prove equally illuminating for his own work, and his representations of war and conflict. On one level, his Dictionary of 1755 is a source of formal exposition in which the meaning of war is anatomized across a range of entries. On another, those who consult its pages are presented with war as an ethical or socio-moral problem, freighted with meanings of a very different kind.
Vibrio cholerae cytotoxin MakA induces noncanonical autophagy resulting in the spatial inhibition of canonical autophagy
Authors: Corkery Dale P. , Nadeem Aftab , Aung Kyaw Min , Hassan Ahmed , Liu Tao , Cervantes-Rivera Ramón , Lystad Alf Håkon , Wang Hui , Persson Karina , Puhar Andrea , Simonsen Anne , Uhlin Bernt Eric , Wai Sun Nyunt , Wu Yao-Wen
Published: October 2020

Autophagy plays an essential role in the defence against many microbial pathogens as a regulator of both innate and adaptive immunity. Among some pathogens, sophisticated mechanisms have evolved that promote their ability to evade or subvert host autophagy. Here, we describe a novel mechanism of autophagy modulation mediated by the recently discovered Vibrio cholerae cytotoxin, MakA. pH-dependent endocytosis of MakA by host cells resulted in the formation of a cholesterol-rich endolysosomal membrane aggregate in the perinuclear region. Aggregate formation induced the noncanonical autophagy pathway driving unconventional LC3 lipidation on endolysosomal membranes. Subsequent sequestration of the ATG12-ATG5-ATG16L1 E3-like enzyme complex required for LC3 lipidation at the membranous aggregate resulted in an inhibition of both canonical autophagy and autophagy-related processes including the unconventional secretion of IL-1β. These findings identify a novel mechanism of host autophagy modulation and immune modulation employed by V. cholerae during bacterial infection.
Orientation to polarized light in tethered flying honeybees
Authors: Kobayashi Norihiro , Okada Ryuichi , Sakura Midori
Published: October 2020

Behavioral responses of honeybees to a zenithal polarized light stimulus were observed using a tethered animal in a flight simulator. Flight direction of the bee was recorded by monitoring the horizontal movement of its abdomen, which was strongly anti-correlated with its torque. When the e-vector orientation of the polarized light was rotated clockwise or counterclockwise, the bee responded with periodic right-and-left abdominal movements; however, the bee did not show any clear periodic movement under the static e-vector or depolarized stimulus. The steering frequency of the bee was well coordinated with the e-vector rotation frequency of the stimulus, indicating that the flying bee oriented itself to a certain e-vector orientation, i.e., exhibited polarotaxis. The percentage of bees exhibiting clear polarotaxis was much smaller under the fast stimulus (3.6 ° s−1) compared with that of the slow stimulus (0.9 or 1.8 ° s−1). The bee did not demonstrate any polarotactic behavior after the dorsal rim region of its eyes, which mediates insect polarization vision in general, was bilaterally covered with black paint. Preferred e-vector orientations under the clockwise stimulus varied among individuals and distributed throughout -90 to 90°. Some bees showed similar preferred e-vector orientations for clockwise and counterclockwise stimuli whereas others did not. Our results strongly suggest that the flying honeybees utilize the e-vector information from the skylight to deduce their heading orientation for navigation.
An Ethanolic Extract of Artemisia dracunculus L. Enhances the Metabolic Benefits of Exercise in Diet-induced Obese Mice
Authors: ALLERTON TIMOTHY D. , KOWALSKI GREG M. , STAMPLEY JAMES , IRVING BRIAN A. , LIGHTON JOHN R. B. , FLOYD Z. ELIZABETH , STEPHENS JACQUELINE M.
Published: October 2020

Purpose

The purpose of this study was to determine the effect of an ethanolic extract of Artemisia dracunculus L. (5011) combined with exercise on in vivo glucose and fat metabolism in diet-induced obese male mice.

Methods

After 8 wk of high-fat diet (HFD) feeding, 52 mice were randomly allocated to a voluntary wheel running group (HFD Ex), a 5011 + HFD sedentary group (5011 Sed), a 5011 + HFD Ex (5011 Ex), or an HFD sedentary group (HFD Sed) for 4 wk. Real-time energy expenditure and substrate utilization were measured by indirect calorimetry. A stable isotope glucose tolerance test was performed before and after the 4-wk wheel running period to determine changes in endogenous glucose production and glucose disposal. We also performed an analysis of genes and proteins associated with the early response to exercise and exercise adaptations in skeletal muscle and liver.

Results

When compared with HFD Ex mice, 5011 Ex mice had increased fat oxidation during speed- and distance-matched wheel running bouts. Both HFD Ex and 5011 Ex mice had reduced endogenous glucose during the glucose tolerance test, whereas only the 5011 Sed and the 5011 Ex mice had improved glucose disposal after the 4-wk experimental period when compared with HFD Sed and HFD Ex mice. 5011 Ex mice had increased Pgc1-α and Tfam expression in skeletal muscle when compared with HFD Ex mice, whereas Pdk4 expression was reduced in the liver of HFD Ex and 5011 Ex mice.

Conclusions

Our study demonstrates that 5011, an ethanolic extract of A. dracunculus L., with a history of medicinal use, enhances the metabolic benefits of exercise to improve in vivo fat and glucose metabolism.
Exercise Intolerance in Cystic Fibrosis: Importance of Skeletal Muscle
Authors: RODRIGUEZ-MIGUELEZ PAULA , SEIGLER NICHOLE , ISHII HARUKI , CRANDALL REVA , MCKIE KATHLEEN T. , FORSEEN CARALEE , HARRIS RYAN A.
Published: October 2020

Purpose

Exercise intolerance, evaluated by O2 consumption, predicts mortality in cystic fibrosis (CF). People with CF exhibit skeletal muscle dysfunctions that may contribute to an imbalance between O2 delivery and utilization. Sildenafil, a phosphodiesterase type 5 inhibitor, increases blood flow and improves O2 consumption, although the exact mechanisms in CF have yet to be elucidated. Thus, we hypothesized that exercise intolerance in CF is limited primarily by an impaired skeletal muscle O2 utilization, and sildenafil improves exercise tolerance in CF by addressing this mismatch between O2 demand and extraction.

Methods

Fifteen individuals with mild to moderate CF and 18 healthy controls completed an incremental exercise test and measurements of gaseous exchange, chronotropic response, hemodynamics, and O2 extraction and utilization. People with CF also completed a 4-wk treatment with sildenafil with a subsequent follow-up evaluation after treatment.

Results

Skeletal muscle O2 extraction and utilization during exercise were reduced in people with CF when compared with controls. Exercise capacity in our CF population was minimally limited by hemodynamic or chronotopic responses, whereas peripheral O2 extraction was more closely associated with exercise capacity. The study also demonstrated that 4 wk of sildenafil improved skeletal muscle O2 utilization during exercise to similar values observed in healthy individuals.

Conclusions

Individuals with mild to moderate CF exhibit exercise intolerance secondary to a reduction in O2 utilization by the exercising skeletal muscle. The present study demonstrated that 4 wk of sildenafil treatment improves the capacity of the skeletal muscle to use O2 more efficiently during exercise. Findings from the present study highlight the importance of targeting skeletal muscle O2 utilization to improve exercise tolerance in CF.
The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days
Authors: Janiaud Perrine , Axfors Cathrine , van't Hooft Janneke , Saccilotto Ramon , Agarwal Arnav , Appenzeller-Herzog Christian , Contopoulos-Ioannidis Despina G. , Danchev Valentin , Dirnagl Ulrich , Ewald Hannah , Gartlehner Gerald , Goodman Steven N. , Haber Noah A. , Ioannidis Angeliki Diotima , Ioannidis John P. A. , Lythgoe Mark P. , Ma Wenyan , Macleod Malcolm , Malički Mario , Meerpohl Joerg J. , Min Yan , Moher David , Nagavci Blin , Naudet Florian , Pauli-Magnus Christiane , O'Sullivan Jack W. , Riedel Nico , Roth Jan A. , Sauermann Mandy , Schandelmaier Stefan , Schmitt Andreas M. , Speich Benjamin , Williamson Paula R. , Hemkens Lars G.
Published: October 2020

Background: Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic.

Methods:Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing any intervention to treat or prevent COVID-19, systematically identified in trial registries, preprint servers, and literature databases. A survey was conducted of all trials to assess their recruitment status up to July 6, 2020.

Results:Most of the 689 trials (overall target sample size 396,366) were small (median sample size 120; interquartile range [IQR] 60-300) but randomized (75.8%; n=522) and were often conducted in China (51.1%; n=352) or the USA (11%; n=76). 525 trials (76.2%) planned to include 155,571 hospitalized patients, and 25 (3.6%) planned to include 96,821 health-care workers. Treatments were evaluated in 607 trials (88.1%), frequently antivirals (n=144) or antimalarials (n=112); 78 trials (11.3%) focused on prevention, including 14 vaccine trials. No trial investigated social distancing. Interventions tested in 11 trials with >5,000 participants were also tested in 169 smaller trials (median sample size 273; IQR 90-700). Hydroxychloroquine alone was investigated in 110 trials. While 414 trials (60.0%) expected completion in 2020, only 35 trials (4.1%; 3,071 participants) were completed by July 6. Of 112 trials with detailed recruitment information, 55 had recruited <20% of the targeted sample; 27 between 20-50%; and 30 over 50% (median 14.8% [IQR 2.0-62.0%]).

Conclusions:The size and speed of the COVID-19 clinical trials agenda is unprecedented. However, most trials were small investigating a small fraction of treatment options. The feasibility of this research agenda is questionable, and many trials may end in futility, wasting research resources. Much better coordination is needed to respond to global health threats.
Supplementation of rice husk activated charcoal in feed and its effects on growth and histology of the stomach and intestines from giant trevally, Caranx ignobilis
Authors: Firdus Firdus , Samadi Samadi , Muhammadar Abdullah A. , Sarong Muhammad A. , Muchlisin Zainal A. , Sari Widya , Mellisa Siska , Satria Satria , Boihaqi Boihaqi , Batubara Agung Setia
Published: October 2020

Background:Research on supplementing feed with rice husk activated charcoal was carried out to determine the effect of variations in the concentration of rice husk activated charcoal on the growth and histological features of theCaranx ignobilisintestine.

Methods:This study used an experimental method with a completely randomized design consisting of six treatments and four replications, including adding activated charcoal to feed at concentrations of 0%, 1%, 1.5%, 2%, 2.5%, and 3% for 42 days. The measured parameters included daily growth rate (DGR), specific growth rate (SGR), absolute growth rate (AGR), feed conversion ratio (FCR), feed efficiency (FE), survival rate (SR), length of foveola gastrica, width of foveola gastrica, length of intestinal villi, and width of intestinal villi. Data were analyzed statistically using one-way analysis of variance and Duncan’s test.

Results:The results showed that supplementing fish feed with rice husk activated charcoal at different concentrations significantly affected the values of DGR, AGR, FCR, FE, SR, length of the foveola gastrica, length of the villous intestine, and width of the villous intestine, but did not significantly affect SGR or foveola gastrica width.

Conclusion:The 2% rice husk activated charcoal treatment showed the best results for all parameters.
Electronic bibliographic guide: a Practical guide for library workers
Authors: Pankova Elena , Berkutova Lyalya
Published: October 2020

Creating an electronic bibliographic manual is time-consuming, but very exciting. By taking the first step with this book, you will be able to master other programs and technologies. The guide will consistently guide you through all the stages of creating an electronic bibliographic manual using standard Word tools. The second edition is supplemented with a Chapter on bibliographic manuals, updated technological capabilities of modern software, and takes into account the rules of the new GOST for compiling a bibliographic description. For library staff and bibliographers, students and teachers, as well as anyone interested in compiling bibliographic manuals, including electronic ones.
History of Russian literature: from the middle Ages to modernism (propaedeutic course)
Authors: Meskin Vladimir , Gavril'chenko Oksana , Trofimova Nina
Published: October 2020

The textbook introduces Russian fine literature from the era of its origin to the beginning of the XX century, with historical factors that influenced the processes that took place in it. Its authors are experts in each of the stated theme. Acquaintance with each historical and literary stage begins with its cultural review, followed by pages devoted to the work of the most prominent artists of the word of the period under review. At the same time, one chronological review follows from another, so that the history of culture and literature is presented not dotted, but chronologically linear, in the dynamics of interrelated processes. Meets the requirements of the Federal state educational standards of higher education of the latest generation. The textbook is written in the genre of propaedeutics and is intended primarily for foreign students studying at preparatory departments and faculties. it will be useful for students of non-philological profile, students of secondary special educational institutions, as well as for anyone interested in Russian literature.
Fundamentals of costume design theory
Authors: KOZLOVA TAT'YaNA
Published: October 2020

Theoretical questions of costume shaping, periodicity of its forms and cyclical structure development are presented. The process of creating industrial clothing collections is considered. The principles of designing individual parts of the costume are given.

For students studying in the direction of training 54.03.03 art of costume and textiles"."
Organizational Learning Processes and Outcomes: Major Findings and Future Research Directions
Authors: Argote Linda , Lee Sunkee , Park Jisoo
Published: October 2020

We trace the evolution of research on organizational learning. As organizations acquire experience, their performance typically improves at a decreasing rate. Although this learning-curve pattern is found in many industries, organizations vary in the rate at which they learn. In order to understand this variation, we separate organizational learning into four processes: search, knowledge creation, knowledge retention, and knowledge transfer. Within each process, we present research on how dimensions of experience and of the organizational context affect learning processes and outcomes. Our goals are to describe major findings and to identify opportunities for future research. The article concludes with a discussion of research directions that are likely to be productive in the future. These directions include investigating how new technological and organizational developments are likely to affect organizational learning.

This paper was accepted by David Simchi-Levi, Special Section of Management Science: 65th Anniversary.
Maximum Likelihood Estimation by Monte Carlo Simulation: Toward Data-Driven Stochastic Modeling
Authors: Peng Yijie , Fu Michael C. , Heidergott Bernd , Lam Henry
Published: October 2020

A Simulation-Based Approach for Calibrating Stochastic Models
The Discrete Moment Problem with Nonconvex Shape Constraints
Authors: Chen Xi , He Simai , Jiang Bo , Ryan Christopher Thomas , Zhang Teng
Published: October 2020

The discrete moment problem aims to find a worst-case discrete distribution that satisfies a given set of moments. This paper studies the discrete moment problems with additional shape constraints that guarantee the worst-case distribution is either log-concave (LC) or has an increasing failure rate (IFR) or increasing generalized failure rate (IGFR). These classes are useful in practice, with applications in revenue management, reliability, and inventory control. The authors characterize the structure of optimal extreme point distributions and show, for example, that an optimal extreme point solution to a moment problem with m moments and LC shape constraints is piecewise geometric with at most m pieces. Using this optimality structure, they design an exact algorithm for computing optimal solutions in a low-dimensional space of parameters. The authors leverage this structure to study a robust newsvendor problem with shape constraints and compute optimal solutions.
Knee arthroplasty for acute fractures around the knee
Authors: Tampere Thomas , Ollivier Matthieu , Jacquet Christophe , Fabre-Aubrespy Maxime , Parratte Sébastien
Published: October 2020

Results of open reduction and internal fixation for complex articular fractures around the knee are poor, particularly in elderly osteoporotic patients. Open reduction and internal fixation may lead to an extended hospital stay and non-weight-bearing period. This may lead to occurrence of complications related to decubitus such as thrombo-embolic events, pneumonia and disorientation. Primary arthroplasty can be a valuable option in a case-based and patient-specific approach. It may reduce the number of procedures and allow early full weight-bearing, avoiding the above-mentioned complications. There are four main indications: 1) Elderly (osteoporotic) patients with pre-existing (symptomatic) end-stage osteoarthritis. 2) Elderly (osteoporotic) patients with severe articular and metaphyseal destruction. 3) Pathological fractures of the distal femur and/or tibia. 4) Young patients with complete destruction of the distal femur and/or tibia. The principles of knee (revision) arthroplasty should be applied; choice of implant and level of constraint should be considered depending on the type of fracture and involvement of stabilizing ligaments. The aim of treatment is to obtain a stable and functional joint. Long-term data remain scarce in the literature due to limited indications.

Cite this article: EFORT Open Rev 2020;5:713-723. DOI: 10.1302/2058-5241.5.190059
Frontiers in non-union research
Authors: Gómez-Barrena Enrique , Padilla-Eguiluz Norma G. , Rosset Philippe
Published: October 2020

Multifactorial aetiology defines non-unions, with a biological and a mechanical distortion of the timeline of bone healing. Research on new advances to increase osteogenesis and promote non-union healing is strongly directed towards new forms of cell products. Basic science and research on non-union treatments is needed to compile preclinical data on new treatments. Bone marrow concentration and expanded mesenchymal stromal cells still require extensive clinical research to confirm efficacy in non-union treatment. Solid preclinical studies, precise cell product definition and preparation, and appropriate ethical and regulatory approvals are needed to assess new advanced therapy medicinal products.

Cite this article: EFORT Open Rev 2020;5:574-583. DOI: 10.1302/2058-5241.5.190062
Definition and diagnosis of fracture-related infection
Authors: McNally Martin , Govaert Geertje , Dudareva Maria , Morgenstern Mario , Metsemakers Willem-Jan
Published: October 2020

Fracture-related infection (FRI) is common and often diagnosed late. Accurate diagnosis is the beginning of effective treatment. Diagnosis can be difficult, particularly when there are no outward signs of infection. The new FRI definition, together with clear protocols for nuclear imaging, microbiological culture and histological analysis, should allow much better study design and a clearer understanding of infected fractures. In recent years, there has been a new focus on defining FRI and avoiding non-specific, poorly targeted treatment. Previous studies on FRI have often failed to define infection precisely and so are of limited value. This review highlights the essential principles of making the diagnosis and how clinical signs, serum tests, imaging, microbiology, molecular biology and histology all contribute to the diagnostic pathway.

Cite this article: EFORT Open Rev 2020;5:614-619. DOI: 10.1302/2058-5241.5.190072
Individualized surgery in primary total knee arthroplasty
Authors: Karachalios Theofilos , Komnos George A.
Published: October 2020

Total knee arthroplasty (TKA) is a satisfactory procedure for end-stage knee joint pathology. However, there is a significant incidence of unsatisfied patients. In recent years conventional total knee arthroplasty surgical technique has been challenged and a modern trend to respect individual anatomy, alignment and soft tissue laxities has been developed. The indications, limits and outcomes of these modern techniques in selected patients are not well-defined. Modern technology (navigation, patient-specific instrumentation and robotics) has improved accuracy of the osteotomies but their effect on long-term outcomes is still unclear. A technique which respects individual anatomy, laxities and alignment in combination with an implant which is designed to incorporate contemporary knee kinematics, without the use of modern technology, is presented.

Cite this article: EFORT Open Rev 2020;5:663-671. DOI: 10.1302/2058-5241.5.190085
Artificial intelligence in orthopaedics: false hope or not? A narrative review along the line of Gartner’s hype cycle
Authors: Oosterhoff Jacobien H.F. , Doornberg Job N. ,   Machine Learning Consortium
Published: October 2020

Artificial Intelligence (AI) in general, and Machine Learning (ML)-based applications in particular, have the potential to change the scope of healthcare, including orthopaedic surgery. The greatest benefit of ML is in its ability to learn from real-world clinical use and experience, and thereby its capability to improve its own performance. Many successful applications are known in orthopaedics, but have yet to be adopted and evaluated for accuracy and efficacy in patients’ care and doctors’ workflows. The recent hype around AI triggered hope for development of better risk stratification tools to personalize orthopaedics in all subsequent steps of care, from diagnosis to treatment. Computer vision applications for fracture recognition show promising results to support decision-making, overcome bias, process high-volume workloads without fatigue, and hold the promise of even outperforming doctors in certain tasks. In the near future, AI-derived applications are very likely to assist orthopaedic surgeons rather than replace us. ‘If the computer takes over the simple stuff, doctors will have more time again to practice the art of medicine’.76

Cite this article: EFORT Open Rev 2020;5:593-603. DOI: 10.1302/2058-5241.5.190092