bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuity of care between hospital pharmacies and community pharmacies, and costs avoided: a pilot experience in times of COVID-19 in Spain
Authors: Zozaya Néboa , González-Domínguez Almudena , Calvente Natividad , De la Plaza Rita , Herranz Ana , Blanes Antonio , Tamayo Miguel
Published: February 2021

Introduction: In March 2020, due to the pandemic caused by COVID-19, a pilot experience of pharmaceutical continuity of care received by hospital outpatients was launched in Cantabria, a Spanish autonomous community. Thanks to this experience, the medication was dispensed by the hospital pharmacy through the community pharmacy of the patient’s choice. Our objective was to estimate the costs avoided by this practice during the months of April and May 2020.

Methods: The analysis of the economic impact was carried out in terms of saved costs, from the hospital and from the social perspective. Savings associated with the avoided home delivery of medication and avoided labor productivity losses were calculated, as well as the time associated with avoided trips in monetary terms.

Results: A total of 2,249 hospital-dispensed drugs were delivered through the community pharmacy in the analyzed period, with an average of 57.7 daily deliveries. The experience, which involved one hospital and 262 pharmacies of Cantabria, saved patients 93,305 km in trips to the hospital, associated with an average time saving of 1,374 hours. In terms of costs, the hospital saved on shipments by courier, estimated at €30,205, since it was the community pharmacy and the distribution warehouses that delivered the drugs. From a social perspective, this initiative saved €23,309 due to the trips (€8,907) and productivity losses (€14,402) that were avoided.

Conclusions: This exceptional situation may be a good opportunity to improve the coordination between hospital pharmacies and community pharmacies in Spain, not only during the pandemic but also in the post-COVID-19 era.
Classificação da aptidão cardiorrespiratória de crianças de 5 a 10 anos, através de valores normativos no desempenho do teste yo-yo intermitente nível 1
Authors: Fagundes Whander D'lucca , Nascimento Lucas Evangelista Campos do , Moraes Bruna Lethicia Jubé , Souza Wesley Salviano de , Pita Vinícius da Silva , Silva Rafael Martins , Oliveira Miridan Rodrigues de , Corrêa Hugo de Luca , Pereira Leonardo Costa , Mazzoccante Rafaello Pinheiro
Published: February 2021

Objetivo: propor padrões normativos de classificação da AC através do desempenho no teste Yo-Yo intermitente nível 1 (Yo-Yo) em crianças de 5 a 10 anos de idade. Materiais e métodos: o estudo foi composto por 1.060 crianças de ambos os sexos, para caracterização foi realizado avaliação antropométrica e utilizou-se o Yo-Yo para avaliação da AC. Resultados: as meninas apresentaram maior massa corporal (p<0.005) e menor AC em comparação os meninos (p<0.001), os valores dos quatis com base no despenho do Yo-Yo foram distribuídos em baixo, moderado, alto e muito alto. Conclusão: o presente estudo apresentou uma proposta de valores de referência da AC, a utilização dos valores propostos pelo presente estudo, podem ser um instrumento fundamental no processo de avaliação da AC em crianças por parte de profissionais de saúde e professores.
Transmissão oral da doença de Chagas: Uma revisão de literatura
Authors: Pacheco Luciano Vasconcellos , Santana Leonora Souza , Barreto Breno Cardim , Santos Emanuelle de Souza , Meira Cássio Santana
Published: February 2021

A doença de Chagas, conhecida como tripanossomíase americana, é causada pelo protozoário T. cruzi e endêmica da América Latina, no qual representa um dos principais problemas socioeconômicos da região. As vias de transmissão podem ser vetorial, via oral, por transfusão sanguínea, transplante de órgãos, transmissão congênita ou acidentes laboratoriais. A transmissão oral destaca-se por ser uma das principais causas da doença de Chagas Aguda (DCA) em algumas regiões. Dessa maneira, o trabalho visa descrever os principais surtos epidemiológicos de infecção com o T. cruzi por contaminação oral com base na literatura e identificar as principais fontes, locais e medidas preventivas tomadas frente a estes surtos causados por contaminação oral. A revisão bibliográfica foi realizada nos bancos de dados: Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), portal Scientific Electronic Library Online (SCIELO) e PubMed. Ao fim da seleção, 13 artigos foram utilizados para o desenvolvimento do estudo. Os trabalhos mostraram que os principais alimentos associados à infecção aguda chagásica foram caldo de cana-de-açúcar, açaí, suco de açaí, água contaminada, suco de palmito e suco de goiaba. As principais localidades acometidas foram o Brasil, Pará, Amapá e Amazonas, e outros países latinos americanos como a Guiana Francesa e Venezuela. Além disso, os estudos apontaram às práticas de controle sanitárias, o processo de cozimento, à adoção de medidas estruturais básicas combinadas com a não utilização de iluminação artificial como possíveis medidas à redução do risco de contaminação nessas áreas. Por fim, esse trabalho traz um levantamento que favorece uma melhor caracterização da importância da transmissão oral da doença de Chagas nos últimos 12 anos na América Latina.
Analysis of diaphragm movement, during tidal breathing and during its activation while breath holding, using MRI synchronized with spirometry
Authors: Kolář P , Neuwirth J , Šanda J , Suchánek V , Svatá Z , Volejník J , Pivec M
Published: February 2021

Using magnetic resonance imaging (MRI) in conjunction with
synchronized spirometry we analyzed and compared diaphragm
movement during tidal breathing and voluntary movement of the
diaphragm while breath holding. Breathing cycles of 16 healthy
subjects were examined using a dynamic sequence (77 slices in
sagittal plane during 20 s, 1NSA, 240x256, TR4.48, TE2.24,
FA90, TSE1, FOV 328). The amplitude of movement of the apex
and dorsal costophrenic angle of the diaphragm were measured
for two test conditions: tidal breathing and voluntary breath
holding. The maximal inferior and superior positions of the
diaphragm were subtracted from the corresponding positions
during voluntary movements while breath holding. The average
amplitude of inferio-superior movement of the diaphragm apex
during tidal breathing was 27.3±10.2 mm (mean ± SD), and
during voluntary movement while breath holding was 32.5±16.2
mm. Movement of the costophrenic angle was 39±17.6 mm
during tidal breathing and 45.5±21.2 mm during voluntary
movement while breath holding. The inferior position of the
diaphragm was lower in 11 of 16 subjects (68.75 %) and
identical in 2 of 16 (12.5 %) subjects during voluntary movement
compared to the breath holding. Pearson’s correlation coefficient
was used to demonstrate that movement of the costophrenic
angle and apex of the diaphragm had a linear relationship in both
examined situations (r=0.876). A correlation was found between
the amplitude of diaphragm movement during tidal breathing and
lung volume (r=0.876). The amplitude of movement of the
diaphragm with or without breathing showed no correlation to
each other (r=0.074). The movement during tidal breathing
shows a correlation with the changes in lung volumes. Dynamic
MRI demonstrated that individuals are capable of moving their
diaphragm voluntarily, but the amplitude of movement differs
from person to person. In this study, the movements of the
diaphragm apex and the costophrenic angle were synchronous
during voluntary movement of the diaphragm while breath
holding. Although the sample is small, this study confirms that
the function of the diaphragm is not only respiratory but also
postural and can be voluntarily controlled.
Reduced susceptibility to ischemia-induced arrhythmias in the preconditioned rat heart is independent of PI3-kinase/Akt
Authors: Ravingerová T , Matejíková J , Pancza D , Kolář F
Published: February 2021

We examined the involvement of phosphatidylinositol 3-kinase
(PI3K) and its effector protein kinase B (Akt) in cardioprotective
effects of ischemic preconditioning (PC) with particular regards to
its role in the protection against ischemia-induced arrhythmias in
isolated perfused rat heart. PI3K/Akt inhibitor wortmannin
(100 nM) was administered 15 min prior to 30-min regional (left
anterior descending coronary artery occlusion) ischemia for the
study of ischemic arrhythmias in the hearts perfused at constant
coronary flow or prior to 30-min global ischemia followed by 2-h
reperfusion for the infarct size (IS) determination (tetrazolium
staining) in the hearts perfused at constant pressure. PC
procedure (one cycle of ischemia/reperfusion, 5 min each)
significantly reduced the total number of ventricular premature
complexes (PVC) and severity of arrhythmias (arrhythmia score;
AS) over the whole period of left anterior descending coronary
artery occlusion in comparison with non-PC controls (PVC
166±40; AS 1.6±0.2 vs. 550±60 and 3.2±0.2; respectively;
P<0.05). In a setting of global ischemia/reperfusion, PC
decreased IS (in % of the left ventricle, LV) by 73 %.
Pretreatment with wortmannin modified neither
arrhythmogenesis nor IS in the non-PC hearts. Bracketing of PC
with wortmannin did not abolish antiarrhythmic protection (PVC
92±25; AS 1.7±0.2; P<0.05 vs. non-PC hearts). On the other
hand, wortmannin increased IS/LV in the PC hearts to 24±1.2 %
as compared with 9 ± 0.6 % in the untreated ones (P<0.05). In
conclusion, PI3K/Akt inhibition did not affect reduced
arrhythmogenesis during ischemia in the PC hearts indicating
that in contrast to its positive role in the irreversible myocardial
injury, PI3K/Akt activity is not required for protection induced by
PC against ischemic arrhythmias in the rat heart.
PENGARUH PELVIC ROCKING EXERCISES MENGGUNAKAN BIRTHING BALL PADA IBU BERSALIN KALA I TERHADAP KEMAJUAN DAN LAMA PERSALINAN
Authors: Jamila Fidatul
Published: February 2021

Angka mortalitas dan mordibitas pada ibu hamil, ibu bersalian dan ibu nifas yang cukup tinggi masih menjadi permasalahan besar terutama bagi negara berkembang seperti di Indonesia. Pada ibu dengan persalinan lama, beresiko terjadi perdarahan karena atoni uterus, laserasi jalan lahir, infeksi, kelelahan dan syok, sementara pada bayi terjadi peningkatan angka kematian, penurunan skor APGAR, trauma dan infeksi. Insiden persalinan lama dapat diminimalkan dengan latihan fisik dan persiapan psikologis. Pelvic Rocking Exercises (PRE) adalah latihan untuk menguatkan pinggang dan panggul. Penelitian ini adalah quasi experiment dengan desain post test only control group. Responden adalah 36 ibu inpartu dengan usia kehamilan 36 – 40 minggu dibagi dalam 2 kelompok perlakuan dengan PRE dan kelompok kontrol. PRE sangat efektif dalam memperpendek waktu kemajuan persalinan kala I fase aktif dengan nilai Sig.(2-tailed) 0,026 < α 0.0.  PRE juga efektif dalam memperpendek lama persalinan kala II dengan nilai Sig.(2-tailed) 0.005 < α 0.05 dengan. Dari hasil penelitian disimpulkan bahwa PRE efektif memperpendek waktu kemajuan persalinan kala I dan lama persalinan kala II persalinan pada primigravida.
Digital labour in the Philippines: Emerging forms of brokerage
Authors: Soriano Cheryll Ruth
Published: February 2021

This article examines and theorises the relationships across three distinct forms of labour brokerage emerging in the digital platform labour economy: platform intermediation, ‘skill-making’, and ‘re-outsourcing’. Drawing from a four-year digital ethnography on online freelancing and platform labour in the Philippines, one of the largest labour supplying countries globally, I pay special attention to how platform labour control emerges as a process that is constituted in the brokerage relationships at multiple scales between global capital, local capital, community and family units, and emerging organised networks of workers and influencers on social media. The article examines the materiality of platform labour and the local informal economy that give rise to these forms of brokerage. I also describe how brokerage processes set norms and standards in this largely unregulated sector, thereby playing a role in how labour mobility or precarity are made possible and organised. The article seeks to contribute to the knowledge about the digital work system involving a significant number of Filipinos by capturing the situated dialectical power relations of the global spread of platform-mediated labour management.
NEW APPROACHES ON SYMMETRIC GENERALIZED INTUITIONISTIC FUZZY METRIC SPACES
Authors: JEYARAMAN M. , SUGANTHI M.
Published: February 2021

In this paper, we prove the existence and uniqueness of a common fixed point in symmetric generalized intuitionistic fuzzy metric spaces using property (E.A.) or CLRg property. We introduce the new notion for a pair of mappings (f, g) on a generalized intuitionistic fuzzy metric space called weakly commuting of type (Jf ) and R-weakly commuting of type (Jf ).
THE NEW SET DIFFERENCE OPERATION BETWEEN INTERVAL VALUED INTUITIONISTIC FUZZY SETS
Authors: BAL Arif , ÇUVALCIOĞLU Gökhan
Published: February 2021

In this paper, the new set di§erence is deÖned between interval- ued intuitionistic fuzzy sets (IVIFSs).A di§erent perspective is reduced to the formal set di§erence between IVIFSs. This new set difference  between IVIFSs is introduced by using : operation. Instead of comparing this operator with all other set di§erence operations, the set difference operation which is defined by using \ is used.
Some fundamentel properties which are provided and not provided on sets are examined whether satisfy or not satisfy on alpha-operation. By the help of these examinations, it is seen that alpha and beta operations have di§erent prop- erties. The new properties abaout set difference are studied.
Update on Nanoparticle-Based Drug Delivery System for Anti-inflammatory Treatment
Authors: Wang Huailan , Zhou Yunxiang , Sun Qunan , Zhou Chenghao , Hu Shiyao , Lenahan Cameron , Xu Weilin , Deng Yongchuan , Li Gonghui , Tao Sifeng
Published: February 2021

Nanobiotechnology plays an important role in drug delivery, and various kinds of nanoparticles have demonstrated new properties, which may provide opportunities in clinical treatment. Nanoparticle-mediated drug delivery systems have been used in anti-inflammatory therapies. Diseases, such as inflammatory bowel disease, rheumatoid arthritis, and osteoarthritis have been widely impacted by the pathogenesis of inflammation. Efficient delivery of anti-inflammatory drugs can reduce medical dosage and improve therapeutic effect. In this review, we discuss nanoparticles with potential anti-inflammatory activity, and we present a future perspective regarding the application of nanomedicine in inflammatory diseases.
Genes Regulating Spermatogenesis and Sperm Function Associated With Rare Disorders
Authors: Linn Emma , Ghanem Lillian , Bhakta Hanisha , Greer Cory , Avella Matteo
Published: February 2021

Spermatogenesis is a cell differentiation process that ensures the production of fertilizing sperm, which ultimately fuse with an egg to form a zygote. Normal spermatogenesis relies on Sertoli cells, which preserve cell junctions while providing nutrients for mitosis and meiosis of male germ cells. Several genes regulate normal spermatogenesis, some of which are not exclusively expressed in the testis and control multiple physiological processes in an organism. Loss-of-function mutations in some of these genes result in spermatogenesis and sperm functionality defects, potentially leading to the insurgence of rare genetic disorders. To identify genetic intersections between spermatogenesis and rare diseases, we screened public archives of human genetic conditions available on the Genetic and Rare Diseases Information Center (GARD), the Online Mendelian Inheritance in Man (OMIM), and the Clinical Variant (ClinVar), and after an extensive literature search, we identified 22 distinct genes associated with 21 rare genetic conditions and defective spermatogenesis or sperm function. These protein-coding genes regulate Sertoli cell development and function during spermatogenesis, checkpoint signaling pathways at meiosis, cellular organization and shape definition during spermiogenesis, sperm motility, and capacitation at fertilization. A number of these genes regulate folliculogenesis and oogenesis as well. For each gene, we review the genotype–phenotype association together with associative or causative polymorphisms in humans, and provide a description of the shared molecular mechanisms that regulate gametogenesis and fertilization obtained in transgenic animal models.
Integrated Characterization of lncRNA-Immune Interactions in Prostate Cancer
Authors: Hu Wei , Wang Yanru , Fang Zhixiao , He Wei , Li Shengli
Published: February 2021

Prostate cancer is among the top mortality factors in male around the world. Long non-coding RNAs (lncRNAs) have been shown to play crucial roles in tumor biology and immunology. However, lncRNA-immune interactions have not yet examined in prostate cancer. Here, we performed integrated analysis to characterize lncRNA-immune interactions in prostate cancer through multidimensional aspects, including immune-related hallmarks, tumor immunogenomic signatures, immune-related biological processes, immune cells, and immune checkpoints. We dissected the dysregulation of lncRNAs and their clinical relevance in prostate cancer, such as RP11-627G23.1 and RP11-465N4.5. Immune-related hallmarks took up the major parts among top significant lncRNA-hallmark interactions. Our analysis revealed that TGF-β signaling pathway was the most frequent to associate with lncRNAs, which is a signature of immune response in cancer. In addition, immune response and its regulation were the most closely connected immunological processes with lncRNA, implying the regulatory roles of lncRNAs on immune response in prostate cancer. We found that memory resting CD4+ T cells were the most lncRNA-correlated immune cell. LINC00861 was found to be potentially intervening targets of immunotherapy for prostate cancer patients, which was significantly associated with PD-1 and CTLA4. Collectively, we offered a handy resource to investigate regulatory roles of lncRNAs on tumor immunology and the development of clinical utility of lncRNAs in prostate cancer.
Design of Cyclodextrin-Based Functional Systems for Biomedical Applications
Authors: Xu Wanjia , Li Xiumei , Wang Liang , Li Siyuan , Chu Shengnan , Wang Jiachun , Li Yijia , Hou Jinxing , Luo Quan , Liu Junqiu
Published: February 2021

Cyclodextrins (CDs) are a family of α-1,4-linked cyclic oligosaccharides that possess a hydrophobic cavity and a hydrophilic outer surface with abundant hydroxyl groups. This unique structural characteristic allows CDs to form inclusion complexes with various guest molecules and to functionalize with different substituents for the construction of novel sophisticated systems, ranging from derivatives to polymers, metal-organic frameworks, hydrogels, and other supramolecular assemblies. The excellent biocompatibility, selective recognition ability, and unique bioactive properties also make these CD-based functional systems especially attractive for biomedical applications. In this review, we highlight the characteristics and advantages of CDs as a starting point to design different functional materials and summarize the recent advances in the use of these materials for bioseparation, enzymatic catalysis, biochemical sensing, biomedical diagnosis and therapy.
The Link Between Sex Hormones and Susceptibility to Cardiac Arrhythmias: From Molecular Basis to Clinical Implications
Authors: Costa Sarah , Saguner Ardan M. , Gasperetti Alessio , Akdis Deniz , Brunckhorst Corinna , Duru Firat
Published: February 2021

It is well-known that gender is an independent risk factor for some types of cardiac arrhythmias. For example, males have a greater prevalence of atrial fibrillation and the Brugada Syndrome. In contrast, females are at increased risk for the Long QT Syndrome. However, the underlying mechanisms of these gender differences have not been fully identified. Recently, there has been accumulating evidence indicating that sex hormones may have a significant impact on the cardiac rhythm. In this review, we describe in-depth the molecular interactions between sex hormones and the cardiac ion channels, as well as the clinical implications of these interactions on the cardiac conduction system, in order to understand the link between these hormones and the susceptibility to arrhythmias.
Different Human–Dog Interactions in Early Agricultural Societies of China, Revealed by Coprolite
Authors: Zhang Yunan , Sun Guoping , Zhang Dong , Yang Xiaoyan , Wu Xiaohong
Published: February 2021

Dogs served in a variety of capacities in prehistory. After their domestication in Paleolithic hunter-gatherer societies, the emergence of agriculture shifted their partnerships with people. However, the associations between dogs and early farmers are not readily visible in the archaeological record. In the present study, dog coprolites, uncovered from two groups of early agricultural societies in China during the Neolithic Age, the early rice agricultural site of Tianluoshan in the lower Yangtze River, and three early millet-rice mixed agricultural sites of Shuangdun, Yuhuicun, and Houtieying along the middle Huai River, were examined based on the comparisons of lipid and palynological results to reveal different relationships of dogs and humans. The Tianluoshan dogs showed a plant-dominated diet with higher contents of plant sterols and fatty alcohols with longer chain lengths. Dogs may have lived on foraging or been provisioned with refuse for the cleanness purpose. On the contrary, dogs from the sites of Shuangdun, Yuhuicun, and Houtieying showed a meat-dominated diet with higher proportions of animal sterols and short-chain fatty alcohols. It most probably referred to their assistance in hunting and thus being provisioned with meat. Furthermore, activity areas of the dogs also reflect different deployment strategies and agricultural systems, evidenced by pollen spectra from the coprolites. Dogs at Tianluoshan mostly appeared in the rice field area, in correspondence with the labor-consuming rice cultivation as the main targeted resource, showing their participation in daily agricultural activities. On the other hand, high concentrations of pollen from forest and grassland revealed that hunting dogs played a regular role in the early millet-rice mixed farming societies, probably related to the importance of hunting activities in the daily subsistence.
Chronic Intermittent Hypobaric Hypoxia Enhances Bone Fracture Healing
Authors: Zhang Li , Jin Lin , Guo Jialiang , Bao Kai , Hu Jinglue , Zhang Yingze , Hou Zhiyong , Zhang Liping
Published: February 2021

The effect of chronic intermittent hypobaric hypoxia (CIHH) on bone fracture healing is not elucidated. The present study aimed to investigate the role of CIHH on bone fracture healing and the mechanism. The Sprague-Dawley rats were randomly divided into the CIHH group and control group and monitored for 2, 4, or 8 weeks after femoral fracture surgery. Bone healing efficiency was significantly increased in the CIHH group as evidenced by higher high-density bone volume fractions, higher bone mineral density, higher maximum force, and higher stiffness. Histologically, the CIHH group exhibited superior bone formation, endochondral ossification, and angiogenic ability compared with the control group. The expression of HIF-1α and its downstream signaling proteins VEGF, SDF-1/CXCR4 axis were increased by the CIHH treatment. Moreover, the expression of RUNX2, osterix, and type I collagen in the callus tissues were also up-regulated in the CIHH group. In conclusion, our study demonstrated that CIHH treatment improves fracture healing, increases bone mineral density, and increases bone strength via the activation of HIF-1α and bone production-related genes.
Purinergic Signaling in Controlling Macrophage and T Cell Functions During Atherosclerosis Development
Authors: Ferrari Davide , la Sala Andrea , Milani Daniela , Celeghini Claudio , Casciano Fabio
Published: February 2021

Atherosclerosis is a hardening and narrowing of arteries causing a reduction of blood flow. It is a leading cause of death in industrialized countries as it causes heart attacks, strokes, and peripheral vascular disease. Pathogenesis of the atherosclerotic lesion (atheroma) relies on the accumulation of cholesterol-containing low-density lipoproteins (LDL) and on changes of artery endothelium that becomes adhesive for monocytes and lymphocytes. Immunomediated inflammatory response stimulated by lipoprotein oxidation, cytokine secretion and release of pro-inflammatory mediators, worsens the pathological context by amplifying tissue damage to the arterial lining and increasing flow-limiting stenosis. Formation of thrombi upon rupture of the endothelium and the fibrous cup may also occur, triggering thrombosis often threatening the patient’s life. Purinergic signaling, i.e., cell responses induced by stimulation of P2 and P1 membrane receptors for the extracellular nucleotides (ATP, ADP, UTP, and UDP) and nucleosides (adenosine), has been implicated in modulating the immunological response in atherosclerotic cardiovascular disease. In this review we will describe advancements in the understanding of purinergic modulation of the two main immune cells involved in atherogenesis, i.e., monocytes/macrophages and T lymphocytes, highlighting modulation of pro- and anti-atherosclerotic mediated responses of purinergic signaling in these cells and providing new insights to point out their potential clinical significance.
Risk Factors for Mortality of COVID-19 Patient Based on Clinical Course: A Single Center Retrospective Case-Control Study
Authors: Zhang Jing , Wang Zhihua , Wang Xiong , Hu Zhiquan , Yang Chunguang , Lei Ping
Published: February 2021

Background: Epidemiological factors, clinical characteristics, and risk factors for the mortality of COVID-19 patients have been studied, but the role of complementary systems, possible inflammatory and immune response mechanisms, and detailed clinical courses are uncertain and require further study.

Methods: In this single center, retrospective case-control study, we included all COVID-19 inpatients transferred or admitted to Wuhan Tongji Hospital from January 3 to March 30 2020 who had definite clinical outcomes (cured or deceased) with complete laboratory and radiological results. Clinical data were extracted from the electronic medical records, and compared between the cured and deceased patients. ROC curves were used to evaluate the prognostic value of the clinical parameters, and multivariable logistic regression analysis was performed to explore the risk factors for mortality. The correlation between the variables was evaluated by Spearman correlation analysis.

Results: 208 patients were included in this study, 182 patients were cured and discharged, 26 patients died from COVID-2019. Most patients had comorbidities, with hypertension as the most common chronic disease (80; 38%). The most common symptoms at onset were fever (149; 72%), cough (137; 66%), and dyspnea (113; 54%). Elevated leucocytes, neutrophils, inflammatory biomarkers (CRP, ferritin, IL6, IL8, procalcitonin), PT, D-dimer, myocardial enzymes, BUN, decreased lymphocyte and subsets (T cells, CD4 T cells, CD8 T cells, NK cells, T cells + B cells + NK cells), and immunological factors (C3, C4) indicated poor outcome. PT, C3, and T cells were confirmed as independent prognostic factors for mortality by logistic regression models. IL6 and CPR were positively correlated with neutrophils, but negatively with lymphocytes and lymphocyte subsets except B cells. IL8 and ferritin were negatively related to T cells and CD4 T cells. Positive associations existed between C3 and T cells, CD4 T cells, and CD8 T cells, whereas there was no significant correlation between C4 and lymphocyte subsets. PT was found positively correlated with IL6, IL8, and CRP. Reverse correlations were explored between C3, C4, and PT, CK-MB, total bilirubin.

Conclusions: T cells, C3, and PT were identified as independent prognostic factors for mortality. Decreased C3 and C4, dysregulation of lymphocyte subsets and cytokines may lead to death after SARS-CoV-2 infection.
A Matter of Scale: Population Genomic Structure and Connectivity of Fisheries At-Risk Common Dolphins (Delphinus delphis) From Australasia
Authors: Barceló Andrea , Sandoval-Castillo Jonathan , Stockin Karen A. , Bilgmann Kerstin , Attard Catherine R. M. , Zanardo Nikki , Parra Guido J. , Hupman Krista , Reeves Isabella M. , Betty Emma L. , Tezanos-Pinto Gabriela , Beheregaray Luciano B. , Möller Luciana M.
Published: February 2021

An understanding of population structure and connectivity at multiple spatial scales is required to assist wildlife conservation and management. This is particularly critical for widely distributed and highly mobile marine mammals subject to fisheries by-catch. Here, we present a population genomic assessment of a near-top predator, the common dolphin (Delphinus delphis), which is incidentally caught in multiple fisheries across the Australasian region. The study was carried out using 14,799 ddRAD sequenced genome-wide markers genotyped for 478 individuals sampled at multiple spatial scales across Australasia. A complex hierarchical metapopulation structure was identified, with three highly distinct and genetically diverse regional populations at large spatial scales (>1,500 km). The populations inhabit the southern coast of Australia, the eastern coast of Australia, New Zealand, and Tasmania, with the latter also showing a considerable level of admixture to Australia's east coast. Each of these regional populations contained two to four nested local populations (i.e., subpopulations) at finer spatial scales, with most of the gene flow occurring within distances of 50 to 400 km. Estimates of contemporary migration rates between adjacent subpopulations ranged from 6 to 25%. Overall, our findings identified complex common dolphin population structure and connectivity across state and international jurisdictions, including migration and gene flow across the Tasman Sea. The results indicate that inter-jurisdictional collaboration is required to implement conservation management strategies and mitigate fisheries interactions of common dolphins across multiple spatial scales in the Australasian region.
Gallium-68 Ventilation/Perfusion PET-CT and CT Pulmonary Angiography for Pulmonary Embolism Diagnosis: An Interobserver Agreement Study
Authors: Le Pennec Romain , Iravani Amir , Woon Beverley , Dissaux Brieg , Gest Bibiche , Le Floch Pierre-Yves , Salaün Pierre-Yves , Le Gal Grégoire , Hofman Michael S. , Hicks Rodney J. , Le Roux Pierre-Yves
Published: February 2021

Objectives:68Ga Ventilation/Perfusion V/Q PET-CT is a promising imaging tool for pulmonary embolism diagnosis. However, no study has verified whether the interpretation is reproducible between different observers. The aim of this study was to assess the interobserver agreement in the interpretation of V/Q PET-CT for the diagnosis of acute PE, and to compare it to the interobserver agreement of CTPA interpretation.

Methods: Twenty-four cancer patients with suspected acute PE underwent V/Q PET-CT and CTPA within 24 h as part of a prospective pilot study evaluating V/Q PET-CT for the management of patients with suspected PE. V/Q PET-CT and CTPA scans were reassessed independently by four nuclear medicine physicians and four radiologists, respectively. Physicians had different levels of expertise in reading V/Q scintigraphy and CTPA. Interpretation was blinded to the initial interpretation and any clinical information or imaging test result. For each modality, results were reported on a binary fashion. V/Q PET/CT scans were read as positive if there was at least one segmental or two subsegmental mismatched perfusion defects. CTPA scans were interpreted as positive if there was a constant intraluminal filling defect. Interobserver agreement was assessed by calculating kappa (κ) coefficients.

Results: Out of the 24 V/Q PET-CT scans, the diagnostic conclusion was concordantly negative in 22 patients and concordantly positive in one patient. The remaining scan was interpreted as positive by one reader and negative by three readers. Out of the 24 CTPA scans, the diagnostic conclusion was concordantly negative in 16 and concordantly positive in one. Out of the seven remaining scans, PE was reported by one reader in four cases, by two readers in two cases, by three readers in one case. Most of discordant results on CTPA were related to clots reported on subsegmental arteries. Mean kappa coefficient was 0.79 for V/Q PET-CT interpretation and 0.39 for CTPA interpretation.

Conclusions: Interobserver agreement in the interpretation of V/Q PET-CT for PE diagnosis was substantial (kappa 0.79) in a population with a low prevalence of significant PE. Agreement was lower with CTPA, mainly as a result of discrepancies at the level of the subsegmental arteries.
A Retrospective Study of Lung Transplantation in Patients With Lymphangioleiomyomatosis: Challenges and Outcomes
Authors: Zhang Ji , Liu Dong , Yue Bingqing , Ban Le , Zhou Min , Wang Hongmei , Lv Jian , Wu Bo , Zhai Zhenguo , Xu Kai-Feng , Chen Wenhui , Chen Jingyu
Published: February 2021

Background: Lymphangioleiomyomatosis (LAM) is a rare systemic disease that generally leads to a progressive decline in pulmonary function. Experience, especially from the Asian population, including combined drug therapy before and after lung transplantation (LT) in LAM, is still limited. This study aimed to summarize the clinical data from patients with pulmonary LAM who underwent LT at centers in China.

Methods: A retrospective review of all patients with LAM undergoing LT at the two largest centers in China between 2010 and 2018 was conducted. Pre- and posttransplant data were assessed and analyzed.

Results: Overall, 25 patients with LAM underwent bilateral LT. The mean age was 35.0 ± 8.6 years at diagnosis and 36.8 ± 9.3 years at the time of transplant. Before LT, only six patients could complete pulmonary function test; the reachable mean forced expiratory volume in one second (FEV1) before LT was 15.9 ± 6.9%. Twenty-one patients (84%) had a recurrent pneumothorax, four (16.0%) of which required pleurodesis. Eight patients (32%) were treated with sirolimus pretransplant for 3.9 years (1–9 years). The average intra-surgery bleeding volume was 1,280 ± 730 ml in need of a transfusion of 1,316 ± 874 ml due to moderate-to-severe adhesion and pretransplant pleurodesis. The causes of death of four patients (16%) included primary graft dysfunction, bronchial dehiscence with long-term use of sirolimus, and uncontrollable infections. The median follow-up time from LT was 41.1 ± 25.0 months.

Conclusions: LT for LAM patients from the Asian population has been reinforced from the data that we presented. Peri-transplantation use of sirolimus and LAM-related complications should be further defined and under constant surveillance.
Skin Manifestations in COVID-19 Patients: Are They Indicators for Disease Severity? A Systematic Review
Authors: Jamshidi Parnian , Hajikhani Bahareh , Mirsaeidi Mehdi , Vahidnezhad Hassan , Dadashi Masoud , Nasiri Mohammad Javad
Published: February 2021

Introduction: Until now, there are several reports on cutaneous manifestations in COVID-19 patients. However, the link between skin manifestations and the severity of the disease remains debatable. We conducted a systematic review to evaluate the temporal relationship between different types of skin lesions and the severity of COVID-19.

Methods: A systematic search was conducted for relevant studies published between January and July 2020 using Pubmed/Medline, Embase, and Web of knowledge. The following keywords were used: “SARS-CoV-2” or “COVID-19” or “new coronavirus” or “Wuhan Coronavirus” or “coronavirus disease 2019” and “skin disease” or “skin manifestation” or “cutaneous manifestation.”

Results: Out of 381 articles, 47 meet the inclusion criteria and a total of 1,847 patients with confirmed COVID-19 were examined. The overall frequency of cutaneous manifestations in COVID-19 patients was 5.95%. The maculopapular rash was the main reported skin involvement (37.3%) commonly occurred in middle-aged females with intermediate severity of the disease. Forty-eight percentage of the patients had a mild, 32% a moderate, and 20% a severe COVID-19 disease. The mild disease was mainly correlated with chilblain-like and urticaria-like lesions and patients with vascular lesions experienced a more severe disease. Seventy-two percentage of patients with chilblain-like lesions improved without any medication. The overall mortality rate was 4.5%. Patients with vascular lesions had the highest mortality rate (18.2%) and patients with urticaria-like lesions had the lowest mortality rate (2.2%).

Conclusion: The mere occurrence of skin manifestations in COVID-19 patients is not an indicator for the disease severity, and it highly depends on the type of skin lesions. Chilblain-like and vascular lesions are the ends of a spectrum in which from chilblain-like to vascular lesions, the severity of the disease increases, and the patient's prognosis worsens. Those with vascular lesions should also be considered as high-priority patients for further medical care.
Fecal Carriage and Genetic Characterization of CTX-M-1/9/1-Producing Escherichia coli From Healthy Humans in Hangzhou, China
Authors: Chen Jiawei , Chen Sheng , Jiang Yin , Zhang Rong , Cai Jiachang
Published: February 2021

CTX-M-199, a novel chimeric β-lactamase which mediated resistance to sulbactam and tazobactam, was recently identified in Hangzhou, China. This study investigated the prevalence of fecal carriage of bacteria producing CTX-M-199 and other CTX-M-1/9/1-type enzymes among healthy individuals and characterized the genetic features ofblaCTX–M–1/9/1-bearing mobile elements. A total of 74 Enterobacterales strains carrying variousblaCTX–M–1/9/1genes, includingblaCTX–M–64(n= 40, carriage rate of 0.74%),blaCTX–M–199(n= 23, 0.40%),blaCTX–M–123(n= 5, 0.10%), novelblaCTX–M–153(n= 5, 0.10%), andblaCTX–M–132(n= 2, 0.04%), were isolated from 68 out of 5,000 (1.36%) fecal samples of healthy adults in Hangzhou City. Phylogenetic analysis based on whole-genome sequencing data showed that 72blaCTX–M–1/9/1-bearingEscherichia coliisolates were clustered into four major clades, three of which included CTX-M-199 producers. Sixty out of 75blaCTX–M–1/9/1genes were located on plasmids belonging to four Inc types: IncI2, IncI1, IncFIB, and IncHI2. TheblaCTX–M–199genes were harbored by three of the four types of plasmids except for IncHI2. All theseblaCTX–M–1/9/1genes were carried on an ISEcp1-mediated transposition unit. In conclusion, human fecal carriage ofblaCTX–M–1/9/1was low in healthy populations of China. The ISEcp1was commonly associated withblaCTX–M–1/9/1and may mediate its transmission on various mobile elements. Our findings provide insights into the dissemination and the development of further measures for the control of pathogens producing CTX-M-1/9/1-type enzymes.
The Epidemiology, Molecular, and Clinical of Human Adenoviruses in Children Hospitalized With Acute Respiratory Infections
Authors: Wen Shunhang , Lin Zupan , Zhang Yue , Lv Fangfang , Li Haiyan , Zhang Xueya , Lin Li , Zhu Hui-Hui , Xu Zhi , Li Changchong , Zhang Hailin
Published: February 2021

Introduction

Human adenovirus (HAdV) is a common pathogen in children with acute respiratory infections (ARIs). The aim was to describe the epidemiology, molecular, and clinical characteristics of HAdV among children hospitalized with ARIs in Wenzhou in southeastern China.

Methodology

From January 2018 to December 2019, nasopharyngeal swab or sputum specimens were prospectively collected from hospitalized children with ARIs. HAdV was detected using direct immunofluorescence. We used a multiplex PCR assay combined with capillary electrophoresis targeting the hexon gene’s hypervariable region to identify HAdV types 1, 2, 3, 4, 5, 7, 14, 21, 37, 40, 41, and 55. We analyzed the epidemiological, molecular, and clinical data according to the HAdV type.

Results

HAdVs were detected in 1,059 (3.5%) of the total of 30,543 children tested. A total of 947 cases with monotype HAdV identified by the PCR assay were included in the analysis. HAdV-3 (415/947, 43.8%), HAdV-7 (318/947, 33.6%), HAdV-2 (108/947, 11.4%), and HAdV-1 (70/947, 7.4%) were the predominant types. Of the 550 (58.1%) cases detected from December 2018 to August 2019, HAdV-3, and HAdV-7 were the main types. The main diagnoses included 358 cases of pneumonia, 232 cases of tonsillitis, 198 cases of bronchitis, and 159 cases of upper respiratory tract infection (URTI). Among children with pneumonia the main types were HAdV-7 (51.1%), HAdV-3 (36.9%), and HAdV-1 (2.2%). Among children with bronchitis, the main types were HAdV-3 (48.0%), HAdV-7 (28.3%), and HAdV-2 (10.6%). Among children with URTIs, the main types were HAdV-3 (49.7%), HAdV-7 (22.6%), and HAdV-2 (13.2%). Among children with tonsillitis, the main types were HAdV-3 (47.4%), HAdV-2 (22.4%), and HAdV-7 (18.5%). In total, 101 (55.2%) patients required supplemental oxygen, 15 (8.2%) required critical care, and 1 child (0.5%) with HAdV-7 pneumonia died.

Conclusion

HAdV-3 -7, -2, and -1 were the predominant types identified in hospitalized children with ARIs in Wenzhou. From December 2018 to August 2019, there were outbreaks of HAdV-3 and -7. There were significant differences in HAdV types among children with pneumonia, tonsillitis, bronchitis, and URTI. HAdV-7 can cause more severe pneumonia in children than HAdV-3.
The Integrative Analysis Identifies Three Cancer Subtypes and Stemness Features in Cutaneous Melanoma
Authors: Wang Xiaoran , Wan Qi , Jin Lin , Liu Chengxiu , Liu Chang , Cheng Yaqi , Wang Zhichong
Published: February 2021

Background: With the growing uncovering of drug resistance in melanoma treatment, personalized cancer therapy and cancer stem cells are potential therapeutic targets for this aggressive skin cancer.

Methods: Multi-omics data of cutaneous melanoma were obtained from The Cancer Genome Atlas (TCGA) database. Then, these melanoma patients were classified into different subgroups by performing "CancerSubtypes" method. The differences of stemness indices (mRNAsi and mDNAsi) and tumor microenvironment indices (immune score, stromal score, and tumor purity) among subtypes were investigated. Moreover, the Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms were performed to identify a cancer cell stemness feature, and the likelihood of immuno/chemotherapeutic response was further explored.

Results: Totally, 3 specific subtypes of melanoma with different survival outcomes were identified from TCGA. We found subtype 2 of melanoma with the higher immune score and stromal score and lower mRNAsi and tumor purity score, which has the best survival time than the other subtypes. By performing Kaplan–Meier survival analysis, we found that mRNAsi was significantly associated with the overall survival time of melanomas in subtype 2. Correlation analysis indicated surprising associations between stemness indices and subsets of tumor-infiltrating immune cells. Besides, we developed and validated a prognostic stemness-related genes feature that can divide melanoma patients into high- and low-risk subgroups by applying risk score system. The high-risk group has a significantly shorter survival time than the low-risk subgroup, which is more sensitive to CTLA-4 immune therapy. Finally, 16 compounds were screened out in the Connectivity Map database which may be potential therapeutic drugs for melanomas.

Conclusion: Thus, our finding provides a new framework for classification and finds some potential targets for the treatment of melanoma.
Multiple Regionalized Genes and Their Putative Networks in the Interpeduncular Nucleus Suggest Complex Mechanisms of Neuron Development and Axon Guidance
Authors: García-Guillén Isabel M. , Alonso Antonia , Puelles Luis , Marín Faustino , Aroca Pilar
Published: February 2021

The interpeduncular nucleus (IPN) is a highly conserved limbic structure in the vertebrate brain, located in the isthmus and rhombomere 1. It is formed by various populations that migrate from different sites to the distinct domains within the IPN: the prodromal, rostral interpeduncular, and caudal interpeduncular nuclei. The aim here was to identify genes that are differentially expressed across these domains, characterizing their putative functional roles and interactions. To this end, we screened the 2,038 genes in the Allen Developing Mouse Brain Atlas database expressed at E18.5 and we identified 135 genes expressed within the IPN. The functional analysis of these genes highlighted an overrepresentation of gene families related to neuron development, cell morphogenesis and axon guidance. The interactome analysis within each IPN domain yielded specific networks that mainly involve members of the ephrin/Eph and Cadherin families, transcription factors and molecules related to synaptic neurotransmission. These results bring to light specific mechanisms that might participate in the formation, molecular regionalization, axon guidance and connectivity of the different IPN domains. This genoarchitectonic model of the IPN enables data on gene expression and interactions to be integrated and interpreted, providing a basis for the further study of the connectivity and function of this poorly understood nuclear complex under both normal and pathological conditions.
Refining the Behavioral Phenotype of Angelman Syndrome: Examining Differences in Motivation for Social Contact Between Genetic Subgroups
Authors: Heald Mary , Adams Dawn , Walls Emily , Oliver Christopher
Published: February 2021

Angelman syndrome (AS) is caused by loss of information from the 15q11.2-13 region on the maternal chromosome with striking phenotypic difference from Prader–Willi syndrome in which information is lost from the same region on the paternal chromosome. Motivation for social contact and sensory seeking behaviors are often noted as characteristics of the phenotype of AS and it has been argued that the strong drive for social contact supports a kinship theory interpretation of genomic imprinting. In this study we developed an experimental paradigm for quantifying the motivation for social contact in AS and examined differences across the genetic subtypes that cause AS [deletion, imprinting centre defect (ICD), uniparental disomy and UBE3A mutation]. Using single case experimental designs we examined the rate of acquisition of behavioral responses using operant learning paradigms for 21 children with AS whilst systematically varying the nature of social and sensory reinforcement. Variability in rates of acquisition was influenced by the nature of rewarding stimuli. Across the total sample both sensory stimuli and social contact could increase the rate of rewarded behavior with difference between children in the most effective reward. A striking difference in the rewarding properties of social contact across genetic subtypes was evidenced by non-deletion genetic causes of AS showing significantly higher rates of responding than the deletion cause in the social reinforcement paradigm. The results indicate that reinforcer assessment can beneficially inform behavioral interventions and that within syndrome variability in the behavioral phenotype of AS is likely driven by genetic difference. The non-deletion cause of AS, and particularly the ICD group, may be the optimal group for further study of genomic imprinting.