bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation of Skeletal Muscle-derived Cells Modeling Neural Crest-Derived Stem Cells for Therapeutic Use in Regenerative Periodontology
Authors: Grimm Wolf-Dieter , Didenko5 Nikolaj , Dhingra Kunaal , Dolgalev Alexander , Enukashvily Natella , Fritsch Tilman , Giesenhagen5 Bernd , Ivolgin Dmitriy , Vukovic Marco Alexander
Published: November 2020

Periodontitis is microbial infection affecting periodontium, the tooth supporting structure and affects >743 million people worldwide. Neural crest-derived stem cells (NCSCs) hold the promise to regenerate the damaged periodontium. These cells have been identified within adult adipose tissue, periodontal ligament, and palatal tissue. Typical enzymatic isolation protocols are expensive, time consuming and often not clinically compliant. Enzyme-free, mechanical dissociation has been suggested as an alternative method of generating cell suspensions required for cell separation and subsequent expansion ex vivo. In our study, samples of rat skeletal muscle tissue were used to appraise the suitability of a novel mincing method of mechanical dissociation against enzymatic digestion with collagenase and dispase. Skeletal muscle is readily available and has been shown to contain NCSC populations. We used a Rigenera-Human Brain Wave® prototype mincer to produce a suspension of skeletal muscle-derived cells modeling NCSCs. We have compared the resulting cell cultures produced via mechanical dissociation and enzymatic dissociation, producing single cell suspensions suitable for Magnetic Cell Sorting (MACs) and Fluorescence-activated cell sorting (FACS). Despite the Countess Automated Cytometry data demonstrating that cell suspensions produced by mechanical dissociation (n=24) contain on average 26.8 times as many viable cells as enzymatic cell suspensions (n=18), enzymatic suspensions produced more successful cell cultures. Spheroids and subsequently adherent cells formed from 4 enzymatic cell suspensions (44.4%) vs. 1 mechanical cell suspension (8.3%). Enzymatic digestion protocols formed spheroids faster and more plentifully than mechanical cell suspensions. Adherent cells and spheroids isolated via both methods appear morphologically similarly to NCSCs from our previous studies.
Extended General Relativity for a Curved Universe
Authors: Al-Fadhli Mohammed B.
Published: November 2020

The Planck Legacy recent release revealed the presence of an enhanced lensing amplitude in the cosmic microwave background, which endorses the early universe positive curvature with a confidence level greater than 99%. Although General Relativity performs accurately in the present universe where spacetime is almost flat, its lost boundary term and the need of dark matter/energy might indicate its incompleteness. By utilising the Einstein–Hilbert action, this letter presents new extended field equations considering pre-existing universal curvatures and boundary contributions. The extended field equations are inclusive of Einstein field equations in addition to the boundary and the conformal curvature terms, which could remove the singularities from the theory.
The Basin Stability of Bi-Stable Friction-Excited Oscillators
Authors: Stender Merten , Hoffmann Norbert , Papangelo Antonio
Published: November 2020

Stability considerations play a central role in structural dynamics to determine states that are robust against perturbations during the operation. Linear stability concepts, such as the complex eigenvalue analysis, constitute the core of analysis approaches in engineering reality. However, most stability concepts are limited to local perturbations, i.e. they can only measure a state’s stability against small perturbations. Recently, the concept of basin stability has been proposed as a global stability concept for multi-stable systems. As multi-stability is a well-known property of a range of nonlinear dynamical systems, this work studies the basin stability of bi-stable mechanical oscillators that are affected and self-excited by dry friction. The results indicate how the basin stability complements the classical binary stability concepts for quantifying how stable a state is given a set of permissible perturbations.
C-Type Lectin CD209L/L-SIGN and CD209/DC-SIGN: Cell Adhesion Molecules Turned to Pathogen Recognition Receptors
Authors: Rahimi Nader
Published: November 2020

C-type lectin CD209/DC-SIGN and CD209L/L-SIGN proteins are distinct cell adhesion and pathogen recognition receptors that mediate cellular interactions and recognize a wide range of pathogens including, viruses such as SARS, SARS-CoV-2, bacteria, fungi and parasites. Pathogens exploit CD209L family proteins to promote infection and evade the immune recognition system. CD209L and CD209 are widely expressed in SARS-CoV-2 target organs and can contribute to infection and pathogenesis. CD209L family receptors are highly susceptible to alternative splicing and genomic polymorphism, which may influence virus tropism and transmission in vivo. The carbohydrate-recognition domain (CRD) and the neck/repeat region represent the key features of CD209L family proteins that are also central to facilitating cellular ligand interactions and pathogen recognition. While, the neck/repeat region is involved in oligomeric dimerization, the CRD recognizes the mannose containing structures present on specific glycoproteins such as those found on the SARS-CoV-2 spike protein. Considering the role of CD209L and related proteins in diverse pathogen recognition, this review article discusses the recent advances in the cellular and biochemical characterization of CD209 and CD209L and their roles in viral uptake, which has important implications in understanding the host-pathogen interaction, the viral pathobiology and driving vaccine development of SARS-CoV-2.
High Temperature With Low Humidity or Vice Versa Does Not Affect Performance and Physiology of Laying Hens
Authors: Kim Da-Hye , Lee Yoo-Kyung , Kim Sang-Ho , Lee Kyung-Woo
Published: November 2020

The present study investigated the effect of different ambient temperature and relative humidity (RH) but equal temperature-humidity index (THI) on laying performance, egg quality, heterophil to lymphocyte ratio (H/L ratio), corticosterone (CORT) concentration in blood, yolk and albumen, and plasma biochemical parameters in laying hens. One hundred and twenty commercial hens (Hy-Line Brown) aged 60 weeks were allocated into 2 environmental chambers. Laying hens were subjected to either one of two thermal treatments, i.e., 26ºC and 70% RH (LH75) and 30ºC and 30% RH (HL75) for 28 days. Both thermal treatments had equal THI being 75. Neither LH75 nor HL75 affected (P > 0.05) laying performance including egg production, egg weight, egg mass, feed intake, and feed conversion ratio. Plasma biochemical parameters such as total cholesterol, high-density lipoprotein cholesterol, triglyceride, calcium, magnesium, and phosphorus was not altered (P > 0.05) by thermal treatments. As to the stress indicators, both environment regimes failed (P > 0.05) to affect blood H/L ratio and CORT levels in plasma, yolk and albumen although albumen CORT levels were elevated (P < 0.05) in LH75 vs. HL75 at days 3, 7, and 28. In conclusion, our study suggests that laying hens performed and responded equally when they were exposed to equal THI environment conditioned from either 26ºC and 70% RH or 30ºC and 30% RH. The results of this study will be served as a scientific basis for management decisions and handling under thermally challenging conditions.
AhR and Cancer: from Gene Profiling to Targeted Therapy
Authors: PARIS Anaïs , TARDIF Nina , GALIBERT Marie-Dominique , CORRE Sébastien
Published: November 2020

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that has been shown to be an essential regulator of a broad spectrum of biological activities required for maintaining the body's vital functions. AhR also plays a critical role in tumorigenesis. Its role in cancer is complex, encompassing both pro- and anti-tumorigenic activities. Its level of expression and activity are specific to each tumor and patient, increasing the difficulty of understanding the activating or inhibiting roles of AhR ligands. We explored the role of AhR in tumor cell lines and patients using genomic data sets and discuss the extent to which AhR can be considered as a therapeutic target.
Kluyveromyces marxianus: Current State of Omics Studies, Strain Improvement Strategy and Potential Industrial Implementation
Authors: Ha-Tran Dung Minh , Nguyen Trinh Thi My , Huang Chieh-Chen
Published: November 2020

Bioethanol has been considered as an excellent alternative to fossil fuels since it importantly contributes to the reduced consumption of the crude oil and to the alleviation of environmental pollution [1]. Up to now, the baker yeast Saccharomyces cerevisiae is the most common eukaryotic microorganism used in ethanol production. The inability of S. cerevisiae to grow on pentoses, however, hinders its effective growth on plant biomass hydrolysates, which contain large amounts of C5 and C12 sugars. The industrial-scale bioprocessing requires high temperature bioreactors, diverse carbon sources, and the high titer production of volatile compounds [2]. These criteria indicate that the search for alternative microbes possessing useful traits that meet the required standards of bioethanol production is necessary. Compared to other yeasts, Kluyveromyces marxianus has several advantages over the others, e.g. it could grow on a broad spectrum of substrates (C5, C6 and C12 sugars) [3], tolerate to high temperature, toxin [4,5] and a wide range of pH values [6], and produce volatile short-chain ester [2]. K. marxianus also shows a high ethanol production rate at high temperature and is a Crabtree-negative species [7]. These attributes make K. marxianus a promise as an industrial host for the biosynthesis of biofuels and other valuable chemicals.
Forecast of Growth and Development of Modal Fir Stands in the Lower Angara Region
Authors: Mikhaylov Pavel Mikhaylov , Sultson Svetlana , Goroshko Andrey
Published: November 2020

The paper presents an assessment of the growth dynamics of the modal fir plantations in the Lower Angara region. At present, a vast area of fir forests in the Lower Angara region is characterised by a significant decrease in sustainability due to periodic forest fires, insect pests outbreaks and diseases, which lead to their natural degradation and death. However, the intensity of coniferous stand growth in certain forest site characteristics persists in the long term. Therefore, creating regression models of forest growth and development involving the identification of site conditions is very important both from a practical point of view and for environmental monitoring. The materials of the mass inventory of 3491 stands served as the initial data for studying the processes of fir plantations natural growth. The Hoerl Model function is suitable for the best approximation of stand growth since it is characterised by high levelling factor (from 0.970 to 0.987) and a small standard error (not exceeding 7%). As a result of the research, there have been constructed sketches of the growth rate tables for the modal Siberian fir stands of the third bonitet class of the forb and mossy groups of forest types.
Evaluation of Biomass Yield and Nutritional Composition of Soybean (Glycine Max (L.)Merrill) Varieties Grown in Low Land Areas of Eastern Amhara, Ethiopia
Authors: Asres Abito , Tiruneh Solomon
Published: November 2020

The experiment was conducted in three locations Jari, Chefa and Sirinka of Eastern Amhara to select the best performing varieties, in terms of biomass yield, chemical composition, haulm yield, seed yield and other agronomic characteristics of Glycine max (L.) Merrill grown under the rain- fed condition of lowland areas of Eastern Amhara in a randomized complete block design with tree replications. Twelve released soybean varieties were Afgat ,Belesa-95, Boshe , Cheri , Dhidhessa, Gishama , Gizo, Korme, Pawe-03, katta, Wegayen and Wollo were used as a treatments. The seeds were planted in 40 cm between rows and 10 cm between plants on a plot size of 3.2m*4m. Spacing between blocks and plots were 1 and 0.5m, respectively. The seed rate was 60 kg/ha and a fertilizer rate 100 kg/ha NPS was applied during seed planting. The combined analysis of variance over two years at location Jari for dry matter yield of varieties Afgat, Gizo, Pawe-03, Wogayen and Wollo were significantly higher as compared to other soybean varieties. The combined analysis across locations at Jari and Sirinka (2019-second year) showed that varieties Afgat, Gishama, Gizo, Pawe-03, Wogayen and Wollo had higher dry matter yield and varieties Gishama (3.97 t/ha), Gizo (3.60 t/ha), Pawe-03 (4.04 t/ha) and Wogayen (3.36 t/ha) had higher haulm yield as compared with other varieties. The combined analysis across locations at Jari and Sirinka (2019) showed that varieties Pawe-03(2951 kg/ha), Gizo (2862 kg/ha), Afgat (2859 kg/ha), Gishama (2654 kg/ha),Wollo (2461 kg/ha) and Wogayen (2404 kg/ha) had higher seed yield as compared with other varieties. The variety Wollo gave higher crud protein content in two locations (Jari and Sirinka) .Therefore, varieties Afgat, Pawe-03 and Wollo were recommends for the given areas of Jari , Chefa, Sirinka and could be produced in similar environments for the best of produced optimal amount of dry matter, haulm and seed yield and good protein supplement for production of ruminants.Thus, further researches will be needed to investigate on the utilization of livestock.
On Reduced Consumption of Fossil Fuels in 2020 and Its Consequences in Global Environment and Exergy Demand
Authors: Rashedi A. , Khanam Taslima , Jonkman Mirjam
Published: November 2020

As the world grapples with the COVID-19 pandemic, there has been a sudden and abrupt change in global energy landscape. Traditional fossil fuels that serve as the linchpin of the modern civilization have found their consumption rapidly fell across the most categories due to strict lockdown and stringent measures that have been adopted to suppress the disease. These changes consequently steered various environmental benefits across the world in recent time. The present article is an attempt to investigate these environmental benefits and reversals that have been materialized in this unfolding situation due to reduced consumption of fossil fuels. Life cycle assessment tool has been used hereby to evaluate nine environmental impacts and one energy based impact. These impacts include: ozone formation (terrestrial ecosystems), terrestrial acidification, freshwater eutrophication, marine eutrophication, terrestrial ecotoxicity, freshwater ecotoxicity, marine ecotoxicity, land use, mineral resources scarcity and cumulative exergy demand. Outcomes from the study demonstrate that COVID-19 has delivered impressive changes in global environment and life cycle exergy demand with about 11-25% curtailment in all above-mentioned impacts in 2020 in comparison to their corresponding readings in 2019.
Vitamin D Modulates Intestinal Microbiota in Inflammatory Bowel Diseases
Authors: Battistini Carolina , Ballan Rafael , Herkenhoff Marcos , Saad Susana , Sun Jun
Published: November 2020

Inflammatory bowel disease (IBD) is a chronic disease in the gastrointestinal tract (GIT). IBD include ulcerative colitis (UC), which generally affects only the large intestine mucosa and submucosa, and Crohn’s disease (CD), which may affect any part of the GIT by transmural inflammation. Both UC and CD are associated with an imbalance of the gut microbiota composition and injuries in the intestinal mucosa. The intestinal dysbiosis is related to a reduction in butyrate-producing species, impairing the anti-inflammatory response of the immune system, and is commonly associated with micronutrients deficiency, e.g. vitamin D hypovitaminosis. Vitamin D is involved in several critical functions, including immune cell differentiation, regulation of microbiota, gene transcription, and barrier integrity. Vitamin D supplementation in IBD patients showed promising results in reducing the disease activity and modulating gut microbiota. Vitamin D receptor (VDR) regulates the biological actions of the active vitamin D metabolite, 1α,25-dihydroxyvitamin D3. Evidence supports that the VDR signaling is involved in the genetic, environmental, immune, and microbial aspects of IBD. Low VDR expression and dysfunction of vitamin D/VDR signaling are reported in IBD patients. Vitamin D/VDR deficiency could be considered as a multifunctional susceptibility factor in IBD. Therefore, in this review, we will discuss the progress in clinical studies, mechanism studies on Vitamin D /VDR, and potential use of vitamin D supplementation as adjuvant therapy to restore gut microbiota balance, promote beneficial metabolites, and inhibit inflammation status in patients with IBD.
Influence of a Major Mountainous Landscape Barrier (Mount Cameroon) on the Spread of Metabolic (GSTe2) and Target-Site (Rdl) Resistance Alleles in the African Malaria Vector Anopheles funestus
Authors: Amvongo-Adjia Nathalie , Riveron Jacob M , Njiokou Flobert , Wanji Samuel , Wondji Charles S.
Published: November 2020

Increased levels of insecticide resistance in major malaria vectors such as Anopheles funestus threaten the effectiveness of insecticide-based control programmes. Understanding the landscape features impacting the spread of resistance makers is necessary to design suitable resistance management strategies. Here we examined the influence of the highest mountain in West Africa (Mount Cameroon; 4,100 meters elevation) on the spread of metabolic and target-site resistance alleles in An. funestus populations. Vector composition varied across the four localities surveyed along the altitudinal cline with major vectors exhibiting high parity rate (80.5%). Plasmodium infection rates ranged from 0.79% (An. melas) to 4.67% (An. funestus). High frequencies of GSTe2R (67% - 81%) and RdlR (49% - 90%) resistance alleles were observed in An. funestus throughout the study area, with GSTe2R frequency increasing with altitude whereas the opposite is observed for RdlR. Patterns of genetic diversity and population structure analyses revealed high levels of polymorphisms with 12 and 16 haplotypes respectively for GSTe2 and Rdl. However, the reduced diversity patterns of resistance allele carriers revealed signatures of positive selection on the two genes across the study area irrespective of the altitude. Despite slight variations associated with the altitude, the spread of resistance alleles suggest that control strategies could be implemented against malaria vectors across mountainous landscapes.
Revision Risk After Unipolar or Bipolar Hemiarthroplasty for Femoral Neck Fractures
Authors: Farey John E. , Cuthbert Alana R. , Adie Sam , Harris Ian A.
Published: November 2020

Background: There remains much international practice variation regarding the choice of a unipolar or bipolar prosthesis design for displaced femoral neck fractures that are treated with hemiarthroplasty. The purpose of the present study was to compare revision rates following primary hemiarthroplasty for femoral neck fracture to determine if the unipolar hemiarthroplasty design increases the risk of revision arthroplasty for all causes.

Methods: Instrumental variable analysis was performed with use of data that had been entered into the Australian Orthopaedic Association National Joint Replacement Registry from September 1, 1999, to December 31, 2018. Sixty-two thousand, eight hundred and seventy-five patients with femoral neck fractures that were treated with primary modular unipolar or bipolar hemiarthroplasty procedure were analyzed. Hospital preference for prosthesis design in the 12 months prior to the index procedure was used as an instrument to adjust for unmeasured confounding. The primary outcome was time to first revision for any cause. Secondary analyses were performed on the reason for revision (infection, dislocation, periprosthetic fracture, or acetabular erosion), the use of cement femoral stem fixation, and the type of stem (polished or matte).

Results: Modular unipolar hemiarthroplasty was associated with a higher rate of revision at >2.5 years (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.46 to 2.36; p < 0.001), but there was no difference between the groups before 2.5 years (HR, 0.98; 95% CI, 0.85 to 1.13; p = 0.79). Protective factors for revision included female sex (HR, 0.82; 95% CI, 0.74 to 0.9), use of cemented fixation (HR, 0.69; 95% CI, 0.62 to 0.77), and surgery performed in a public hospital setting (HR 0.79; 95% CI, 0.70 to 0.89). Modular unipolar prostheses had a greater risk of revision for acetabular erosion, particularly in later time periods (HR at ≥5.5 years, 5.10; 95% CI, 2.40 to 10.83; p < 0.001), while being protective against periprosthetic fractures (HR, 0.72; 95% CI, 0.59 to 0.87; p < 0.001) at all time points. There was no difference in terms of the risk of revision for infection, dislocation, or stem type.

Conclusions: Bipolar hemiarthroplasty designs resulted in a lower risk of revision than unipolar designs. Unipolar hemiarthroplasties are justified for patients with femoral neck fracture and a shorter life expectancy (≤2.5 years).

Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Drivers of Prolonged Hospitalization Following Spine Surgery
Authors: Martini Michael L. , Neifert Sean N. , Gal Jonathan S. , Oermann Eric K. , Gilligan Jeffrey T. , Caridi John M.
Published: November 2020

Update

This article was updated on January 13, 2023, because of an incorrect URL for the Disclosure of Potential Conflicts of Interest on page 64.

An erratum has been published: J Bone Joint Surg Am. 2023 Mar 1;105(5):e18.

Background:

Understanding the interactions between variables that predict prolonged hospital length of stay (LOS) following spine surgery can help uncover drivers of this risk in patients. This study utilized a novel game-theory-based approach to develop explainable machine learning models to understand such interactions in a large cohort of patients treated with spine surgery.

Methods:

Of 11,150 patients who underwent surgery for degenerative spine conditions at a single institution, 3,310 (29.7%) were characterized as having prolonged LOS. Machine learning models predicting LOS were built for each patient. Shapley additive explanation (SHAP) values were calculated for each patient model to quantify the importance of features and variable interaction effects.

Results:

Models using features identified by SHAP values were highly predictive of prolonged LOS risk (mean C-statistic = 0.87). Feature importance analysis revealed that prolonged LOS risk is multifactorial. Non-elective admission produced elevated SHAP values, indicating a clear, strong risk of prolonged LOS. In contrast, intraoperative and sociodemographic factors displayed bidirectional influences on risk, suggesting potential protective effects with optimization of factors such as estimated blood loss, surgical duration, and comorbidity burden.

Conclusions:

Meticulous management of patients with high comorbidity burdens or Medicaid insurance who are admitted non-electively or spend clinically indicated time in the intensive care unit (ICU) during their hospitalization course may be warranted to reduce their risk of unanticipated prolonged LOS following spine surgery.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Análisis de texto en Twitter para las elecciones a la Alcaldía de Bogotá 2019
Authors: García-Guerrero Marcela , Aguirre-Peña Laura Sofía
Published: November 2020

Una de las técnicas en el campo de la big data que se utiliza para indagar la relación de las personas con respecto a algún tema en específico es la minería de texto, que consiste en utilizar palabras o textos con el propósito de inferir análisis robustos de una situación. En el presente artículo se presenta un análisis de texto de las interacciones en Twitter por parte de los candidatos y seguidores en los últimos cuatro días de campaña a la Alcaldía de Bogotá 2019, con el fin de analizar el nivel de aceptación que tienen los seguidores frente a las publicaciones de los candidatos en torno a sus campañas en este periodo previo al ejercicio de votación. La técnica utilizada fue análisis de texto, para lo cual se extrajeron los trinos de los seguidores de los candidatos a la Alcaldía de Bogotá mediante el uso del software estadístico R-Studio y API. El resultado muestra cuatro gráficos correspondientes a la frecuencia de palabras de los seguidores de cada candidato. Se inicia con el candidato Miguel Uribe, seguido por el candidato Carlos Galán, luego el candidato Hollman Morris y, finalmente, la candidata Claudia López, de manera que se muestra cómo entre más diversidad de colores y el aumento del tamaño de las palabras mayor es la frecuencia en el uso de estas, lo que genera una mayor comunicación entre el candidato y los seguidores a fin de promover las campañas.
The pattern of stressful life events prior to suicide among the older adults in rural China: a national case-control psychological autopsy study
Authors: Mo Qiqing , Ma Zhenyu , Wang Guojun , Jia Cunxian , Niu Lu , Zhou Liang
Published: November 2020

Background: There is a lack of evidence concerning the stressful life events experienced prior to suicide which may be associated with an increased suicide risk among Chinese rural older adults. The aim of this study was to identify the pattern of stressful life events prior to suicide among the older adults in China.Methods: Twelve counties were randomly selected using two-stage stratified cluster sampling method. Suicide cases aged 60 years and older (n =242) were collected from those counties from June 2014 to September 2015. Matched living controls were selected 1:1 with suicide cases by age, gender, and location. Data were collected using face-to-face interviews by a psychological autopsy method. The Life Event Scale for the Elderly was used to measure the stressful life events prior to suicide/interviews.Results: Approximately 99.6% of suicide cases and 88.4% of controls experienced at least one stressful life event. The suicide group experienced more long-term stressful life events than recent stressful life events. The top three most frequent stressful life events for the suicide group were being diagnosed with chronic disease, hospitalization, and being diagnosed with terminal illness. More female suicide cases experienced the death of a spouse, while more males experienced hospitalization, diagnosis with terminal illness and family poverty. Experiencing at least one stressful life event, an unstable marital status, physical diseases and mental disorders were shown to increase the risk of suicide.Conclusions: Stressful life events were common for the rural older adults, especially long-term stressful life events. The experience of at least one stressful life event can increase suicide risk among this population. More attention should be paid to the rural older adults who experienced more long-term stressful life events and health related life events.
The Effect of Lifestyle and Risk Factor Modification on Occlusive Peripheral Arterial Disease Outcomes: Standard Healthcare vs Structured Programme: for a Randomised Controlled Trial Protocol
Authors: Elfghi Marah , Jordan Fionnuala , Dunne Denise , Gibson Irene , Jones Jennifer , Flaherty Gerard , Sultan Sherif , Tawfick Wael
Published: November 2020

BackgroundPeripheral arterial disease (PAD) affects more than 200 million of the global population. PAD represents a marker for premature cardiovascular events. Patients with PAD, even in the absence of a history of myocardial infarction or ischemic stroke, have approximately the same relative risk of death from cardiovascular causes as patients with a history of coronary or cerebrovascular disease. Despite the high prevalence of PAD and the strong association with cardiovascular morbidity and mortality, patients with PAD are less likely to receive appropriate treatment for their atherosclerotic risk factors than those who are being treated for coronary artery disease.Atherosclerotic risk factor identification and modification play an important role in reducing the number of adverse outcomes among patients with atherosclerosis. Risk reduction therapy decreases the risk of cardiovascular mortality and morbidity in patients with PAD. In this study we aim to evaluate the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors MethodsThis is a randomised, parallel group, active-control trial to compare the effectiveness of the risk factor modification intervention programme to standard healthcare in a tertiary vascular care centre, in the reduction of modified risk factors in PAD patients. The primary outcome of this study is to evaluate the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors at 3 and 12 months. The secondary outcomes are to compare the impact of the programme on clinical outcomes in PAD patients at 12 months. Secondary outcomes include amputation-free survival, clinical improvement, haemodynamic improvement, need for revascularisation procedures, outcomes of revascularisation procedures, changes in quality of life and the incidence of adverse events.DiscussionThis study will provide clear evidence on the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors, through a high quality, well-powered clinical trial.Trial registration This trial was registered (11/07/2017) on the European Clinical Trials Database (EudraCT number 2017-002964-41) and ClinicalTrials.gov (NCT03935776) which was registered on 02 May 2019.
Molecular characterization of the viral structural protein genes in the first outbreak of dengue virus type 2 in Hunan Province, inland China in 2018
Authors: Guan Jiaoqiong , He Zhanlong , Qin Meng , Deng Xialin , Chen Jun , Duan Suqin , Gao Xiaojun , Pan Yue , Chen Junying , Yang Yaping , Feng Shijun , sun Qiangming
Published: November 2020

Background: An unexpected dengue outbreak occurred in the Hunan Province in 2018. This is the first dengue outbreak in this area of inland China, and 172 cases were reported. Methods: To verify the causative agent of this outbreak and investigate gene characterization, the structural protein C/prM/E genes of viruses isolated from local residents were sequenced followed by mutation and phylogenetic analysis. The recombination, selection pressure, potential secondary structure and three-dimensional structure analysis were also performed. Results: Phylogenetic analysis revealed that all epidemic strains were classified as the cosmopolitan DENV-2 genotype, closest to the Zhejiang strain (MH010629, 2017) and then Malaysia strain (KJ806803, 2013). Compared with the DENV-2SS, 151 base substitutions were found in 89 sequences of isolates, which resulted in 20 non-synonymous mutations, of which 17 mutations existed among all samples (two in capsid protein, six in prM/M, and nine in envelope proteins). Moreover, amino acid substitutions at 602th (E322:Q→H) and 670th (E390: N→S) may enhance virulence of the epidemic strains. One new DNA-binding site and five new protein binding sites were observed. Two polynucleotide-binding sites and seven protein binding sites were lost compared with DENV-2SS. Meanwhile, five changes were found in helix regions. Minor changes were observed in helical transmembrane and disordered regions. The 429th amino acid of E proteins was switch from histamine (positively charged) to asparagines (neutral) in all 89 isolate strains. No recombination events or positive selection pressure sites were observed. To our knowledge, this study is the first one to analyze the genetic characteristics of epidemic strain in the first dengue outbreak in Hunan Province, inland China. Conclusions: The causative agent is likely to come from Zhejiang Province, a neighbouring Province where dengue fever broke out in 2017. This study may help to understand the intrinsic geographical relatedness of DENV-2 and contributes to further research on pathogenicity and vaccine development.
Rules of amino acid convergence: Not how many, but who in avian vocal learning clades
Authors: Lee Chul , Cho Seoae , Kim Kyu-Won , Yoo DongAhn , Han Jae Yong , Lee Hong Jo , Gedman Gregory , Audet Jean-Nicholas , Hara Erina , Rivas Miriam , Whitney Osceola , Pfenning Andreas , Kim Heebal , Jarvis Erich
Published: November 2020

Single amino acid variants (SAVs) may provide clues to understanding evolution of traits. A complex trait that has evolved convergently among species is vocal learning, the rare ability to imitate sounds heard and an important component of spoken-language. Here we assessed whether convergent vocal learning bird species have convergent SAVs (CSAVs) that could be associated with their specialized trait. We analyzed avian genomes and identified CSAVs in vocal learners, but also in most species combinations tested. The number of CSAVs among species was proportional to the product of the most recent common ancestor (MRCA; origin) branch lengths of the species in question, and vocal learning birds did not exceed the overall proportion in most test. However, genes with identical CSAVs (iCSAVs) in vocal learning species were uniquely enriched in ‘learning’ functions, and a subset of iCSAV genes were under positive selection and had enriched specialized regulation in vocal learning and their adjacent brain subdivisions. Several top candidate genes converge on the cAMP signaling pathway, including DRD1B and PRKAR2B. Our findings suggest a complex mechanism of amino acid convergences and specialized gene regulation upon which selection acts for specialized convergent traits.
An Estimation of Macroeconomic Energy Rebound, Intensity, and Output Effect: A Fresh Evidence from Pakistan
Authors: Ullah Shafqut , Mahmood Tahir
Published: November 2020

The authors have requested that this preprint be removed from Research Square.
A retrospective study of hemodialysis treated end-stage renal disease patients with renal osteodystrophy-associated fragility fractures
Authors: Xie Lihua , Hu Xuantao , Li Wenzhao , Ouyang Zhengxiao
Published: November 2020

Background: Nephropathy associated metabolic disorder induces high incidence of fragility fracture in end-stage renal disease (ESRD) patients. As the risk factors and prognosis of fragility fracture in ESRD patients are unclear, more research is needed. This study aimed to evaluate various risk factors for ESRD-related fragility fractures, explore factors affecting the prognosis of patients with such fractures, and provide information for prevention and treatment of renal osteopathy to improve the prognosis of patients.Methods: In this retrospective case-control study, the case notes of 521 ESRD patients who received maintenance dialysis for at least 3 months were examined. Finally, 44 patients diagnosed with fragility fractures were assigned to the fragility fracture (FF) group and 192 patients were included in the control group (CG). Demographic information, underlying diseases, nutritional, bone metabolism, and renal function parameters, along with the number and causes of any deaths, were recorded for multiple statistical analysis.Results: The FF group had increased incidences of essential hypertension and diabetes mellitus and higher serum calcium, corrected calcium, alkaline phosphatase, and hemoglobin levels. Immunoreactive parathyroid hormone (iPTH), total cholesterol (TC), and low density lipoprotein (LDL) levels were higher in the CG.Conclusions: Essential hypertension and diabetes, high serum calcium and alkaline phosphatase levels, and reduced iPTH levels were risk factors for fragility fracture in ESRD patients. Maintaining iPTH and serum TC levels may protect against fragility fractures in them. Fragility fractures may yield poor prognosis and shorter lifespan. The presence of fragility fracture was an independent predictor of all-cause death in ESRD patients.
Association Between Modifiable Prehospital Prognostic Factors on Out-Of-Hospital Cardiac Arrest in Different Age Groups
Authors: Huang Jyun-Bin , Lee Kuo-Hsin , Ho Yu-Ni , Tsai Ming-Ta , Wu Wei-Ting , Cheng Fu-Jen
Published: November 2020

Background The prognosis of out-of-hospital cardiac arrest (OHCA) is very poor. While several prehospital factors are known to be associated with improved survival, the impact of prehospital factors on different age groups is unclear. The objective of the study was to access the impact of prehospital factors and pre-existing comorbidities on OHCA outcomes in different age groupsMethods A retrospective observational analysis was conducted using the emergency medical service (EMS) database from January 2015 to December 2019. We collected information on prehospital factors, underlying diseases, and outcome of OHCAs in different age groups. Kaplan-Meier type survival curves and multivariable logistic regression were used to analyze the association between modifiable pre-hospital factors and outcomes. Results A total of 4188 witnessed adult OHCAs were analyzed. For the younger group (age ≦75 years old), after adjustment for confounding factors, EMS response time (odds ratio [OR]=0.860, 95% confidence interval [CI]: 0.811-0.909, p<0.001), public location (OR=1.843, 95% CI: 1.179-1.761, p<0.001), bystander CPR (OR=1.329, 95% CI: 1.007-1.750, p=0.045), attendance by an EMT-Paramedic (OR=1.666, 95% CI: 1.277-2.168, p<0.001), and prehospital defibrillation by automated external defibrillator (AED)(OR=1.666, 95% CI: 1.277-2.168, p<0.001) were prognostic factors for OHCA. For the older group (age >75 years old), age (OR=0.924, CI: 0.880-0.966, p=0.001), EMS response time (OR=0.833, 95% CI: 0.742-0.928, p=0.001), public location (OR=4.290, 95% CI: 2.450-7.343, p<0.001), and attendance by an EMT-Paramedic (OR=2.702, 95% CI: 1.704-4.279, p<0.001) were independent prognostic factors for OHCA.Conclusions There were variations between younger and older OHCA patients. We found that bystander CPR and prehospital defibrillation by AED were independent prognostic factors for younger OHCA patients but not for the older group.
Clinical Relevance of Impaired Consciousness in Accidental Hypothermia: A Japanese Multicenter Retrospective Study
Authors: Fukuda Masahiro , NOZAWA Masahiro , OKADA Yohei , MORITA Sachiko , EHARA Naoki , MIYAMAE Nobuhiro , JO Takaaki , SUMIDA Yasuyuki , OKADA Nobunaga , WATANABE Makoto , TSURUOKA Ayumu , FUJIMOTO Yoshihiro , OKUMURA Yoshiki , KITAMURA Tetsuhisa , MATSUYAMA Tasuku
Published: November 2020

Background: Severe accidental hypothermia (AH) is a life-threatening condition, and early identification can enable transport to an appropriate medical facility. The Swiss staging model has been used to classify patients with AH, but little is known regarding the relationship between the degree of impaired consciousness and core body temperature (BT) in AH. This study aimed to clarify the relationship between the level of consciousness and core BT and determine whether the level of consciousness could be used to predict severe hypothermia and in-hospital mortality among patients with AH.Methods: We retrospectively investigated the clinical relevance of impaired consciousness in AH. We included adult patients with AH and excluded patients with out-of-hospital cardiac arrest. The patients were identified from the J-point registry, which contains information regarding patients treated for AH between April 1, 2011 and March 31, 2016 in any of the 12 participating institutions in Japan. The primary exposure of interest was the level of consciousness at hospital arrival. Odds ratios were calculated for severe hypothermia and in-hospital mortality.Results: Overall, 505 of the 572 patients in the registry were included. Compared to mildly impaired consciousness, the adjusted odds ratio for severe hypothermia was 3.3 (95% confidence interval [CI]: 1.7–6.3) for moderately impaired consciousness and 4.7 (95% CI: 2.4–9.1) for severely impaired consciousness. Severely impaired consciousness as a predictor severe hypothermia had a sensitivity of 0.44 (95% CI: 0.34–0.54), specificity of 0.78 (95% CI: 0.74–0.82), positive likelihood ratio of 2.04, and negative likelihood ratio of 0.71. Compared to mildly impaired consciousness, the adjusted odds ratio for in-hospital mortality was 1.7 (95% CI: 0.95–2.9) for moderately impaired consciousness and 2.1 (95% CI: 1.2–3.8) for severely impaired consciousness.Conclusions: Severely impaired consciousness was a reliable predictor of severe hypothermia and in-hospital mortality in patients with AH. Thus, in an urban out-of-hospital emergency setting, the level of impaired consciousness may be helpful for triaging patients to the appropriate hospital.
Total Saponins of Panax Notoginseng Exhibit Neuroprotection by The Activation of Akt/mTOR Pathway in Vitro and in Vivo
Authors: Wu Dong-Ping , Pan Yu-Wei , Liang Hua-Feng , Tang Gen-Yun , Chen Ming , Liu Guan-Ping , Zhang Li-Li , Fan Chun-Lin , Shi Lei , Ye Wen-Cai , Li ManMei
Published: November 2020

Background: Panax notoginseng (Burkill) F.H.Chen is a traditional Chinese medicine. The present study reports the potential therapeutic effect of total saponins of Panax notoginseng (Burkill) F.H.Chen (TSPN) on ischemic stroke and investigates the underlying mechanisms. To reveal the neuroprotective effect of TSPN on cerebral ischemia-reperfusion injury and the underlying mechanisms.Methods: Oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons was used as a model of neuronal injury. The neuroprotective effect of TSPN was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and Live/Dead cell assay. The morphology of dendrites was detected by immunofluorescence. Rat middle cerebral artery occlusion (MCAO) was used as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological score, tail hang test, TTC staining, and Nissl staining. Western blot analysis, immunohistochemistry or immunofluorescence was used to measure the changes in Akt/mTOR signaling pathway.Results: MTT showed that TSPN had a rescue effect on cortical neurons after OGD/R-treated. Flow cytometry and Live/Dead cell assay indicated that TSPN decreased neuronal apoptosis, and immunofluorescence showed that TSPN restored dendrite morphology of the damaged neurons. Moreover, TSPN down-regulated the expressions of cleaved-Caspase-3 and LC3B-II/LC3B-I, whereas up-regulated the levels of phosphorylated (p)- Akt and p-mTOR. In MCAO model, TSPN rescued defective neurological behavior and reduced infarct volume. Moreover, the expressions of Beclin-1 and LC3B in cerebral ischemic penumbra were down-regulated after the treatment of TSPN, whereas p-mTOR level was up-regulated.Conclusion: TSPN show neuroprotective effects against OGD/R-induced cortical neuronal damage and exhibit potential therapeutic effects on cerebral ischemia in rat MCAO model. Up-regulation of mTOR pathway and inhibition of the autophagic pathway could be the mechanisms that underlie the action of TSPN.
Resuscitative Endovascular Balloon Occlusion of the Aorta is a Risk Factor for Intestinal Necrosis: A Case Report
Authors: Yajima Keitaro , Matsumoto Shokei , Yamazaki Motoyasu
Published: November 2020

BackgroundResuscitative endovascular balloon occlusion of the aorta (REBOA) is effective for temporary hemorrhage control and resuscitative effort, as it enhances cerebral and coronary circulation in trauma patients. However, an inappropriate utilization of REBOA leads to critical complications. Placement of the balloon in Zone 2 of the aorta should be avoided as the occlusion restricts the intestinal blood supply leading to fatal complications. There is a scarcity of case reports on complications associated with endovascular balloon occlusion in the literature. Here, we have presented a rare case in which Zone 2 REBOA contributed to an ischemic complication in a trauma patient.Case presentationA 50-year-old man with severe trauma, who accidentally got buried under a fallen cement wall, was carried to the nearest hospital. Contrast-enhanced computed tomography showed an unstable pelvic fracture that required hemostatic intervention. Prior to being transferred to another hospital, the patient was treated with endovascular balloon placement. A Zone 2 endovascular balloon placement with resuscitative effort accidentally led to insufficient abdominal blood flow and he developed extensive intestinal necrosis. Following surgical intervention, the patient was resuscitated; however, he developed partial intestinal necrosis and was subsequently managed with surgical intestinal resection.ConclusionsBlood supply to the abdominal organs should be considered when deploying the balloon. Further, balloon positioning, aortic occlusion time, and inflation volume should be carefully considered to avoid ischemic complications.
Sampling Strategies to Evaluate the Prognostic Value of a New Biomarker on a Time-to-Event End-Point
Authors: Graziano Francesca , Valsecchi Maria Grazia , Rebora Paola
Published: November 2020

Background: The availability of large epidemiological or clinical data storing biological samples allow to study the prognostic value of novel biomarkers, but efficient designs are needed to select a subsample on which to measure them for parsimony and economical reasons. Two-phase stratified sampling is a flexible approach to perform such sub-sampling, but literature on stratification variables to be used in the sampling and power evaluation is lacking especially for survival data.Methods: We compared the performance of different sampling designs to assess the prognostic value of a new biomarker on a time-to-event end-point, applying a two-phase Cox model weighted by the inverse of the empirical inclusion probability. Results: Our simulation results suggest that case-control stratified (or post stratified) by a surrogate variable of the marker can yield higher performances than simple random, probability proportional to size and case-control sampling. In the presence of high censoring rate, results showed an advantage of nested case-control and counter-matching designs in term of design effect, but their constrain in using a fixed ratio between cases and controls might be disadvantageous. On real data on childhood acute lymphoblastic leukemia, we also found that optimal sampling using pilot data is greatly efficient.Conclusions: Our study suggests that, in our sample, case-control stratified by surrogate and nested case-control yield estimates and power comparable to estimates obtained in the full cohort while strongly decreasing the number of patients required. We recommend to plan the sample size and using sampling designs for exploration of novel biomarker in clinical cohort data.