bluuebunny/crossref_metadata_2025 huggingface dataset:
Society of Behavioral Medicine (SBM) position statement: End the fatal paradox: change the names of our Federal Institutes on Addiction
Authors: Kelly John F , Earnshaw Valerie
Published: December 2020

Evidence demonstrates that exposure to the terms “abuse” and “substance abuser” increases stigmatizing and discriminatory attitudes toward individuals suffering from drug and alcohol problems, ultimately leading to suboptimal clinical care delivery and poorer treatment outcomes. The American Psychiatric Association has dropped the term “abuse” from its diagnostic terminology; therefore, the term provides no advantage in terms of clinical precision or public health communication. Although numerous medical and public health associations have advocated against the term “abuse,” it remains embedded in the very titles of our major federal institutions and administrations whose explicit mission is to alleviate these endemic problems. Congress must act to change the names of the National Institutes of Health on addiction (i.e., NIAAA, NIDA) and related federal institutions (SAMHSA, CSAT). The Society of Behavioral Medicine supports the removal of the term “abuse” from the National Institutes of Health and related federal administrations pertaining to addiction and replacement with more neutral and nonstigmatizing terminology (e.g., disorder). Alternative names for the federal organizations that SBM supports are the “National Institute on Alcohol Use Disorder,” the “National Institute on Drug Use Disorders,” the “Substance Use Disorder and Mental Health Services Administration,” and the “Center for Substance Use Disorder Treatment.”
Characterization ofBotrytis cinereaandB.prunorumFrom Healthy Floral Structures and Decayed ‘Hayward’ Kiwifruit During Post-Harvest Storage
Authors: Riquelme Danae , Aravena Zdenka , Valdés-Gómez Héctor , Latorre Bernardo A. , Díaz Gonzalo A. , Zoffoli Juan Pablo
Published: December 2020

Gray mold is the primary postharvest disease of ‘Hayward’ kiwifruit (Actinidia deliciosa) in Chile, with a prevalence of 33.1% in 2016 and 7.1% in 2017. Gray mold develops during postharvest storage, which is characterized by a soft, light to brown watery decay that is caused by Botrytis cinerea and B. prunorum. However, there is no information on the role of B. prunorum during the development and storage of kiwifruit in Chile. For this purpose, asymptomatic flowers and receptacles were collected throughout fruit development and harvest from five orchards over two seasons in the Central Valley of Chile. Additionally, diseased kiwifruits were selected after storage for 100 days at 0°C and 2 days at 20°C. Colonies of Botrytis sp. with high and low conidial production were consistently obtained from apparently healthy petals, sepals, receptacles, and styles and diseased kiwifruit. Morphological and phylogenetic analysis of three partial gene sequences encoding glyceraldehyde-3-phosphate dehydrogenase, heat shock protein 60, and DNA-dependent RNA polymerase subunit II were able to identify and separate B. cinerea and B. prunorum species. Consistently, B. cinerea was predominantly isolated from all floral parts and fruit in apparently healthy tissue and diseased kiwifruit. During full bloom, the highest colonization by B. cinerea and B. prunorum was obtained from petals, followed by sepals. In storage, both Botrytis species were isolated from the diseased fruit (n = 644), of which 6.8% (n = 44) were identified as B. prunorum. All Botrytis isolates grew from 0°C to 30°C in vitro and were pathogenic on kiwifruit leaves and fruit. Notably, B. cinerea isolates were always more virulent than B. prunorum isolates. This study confirms the presence of B. cinerea and B. prunorum colonizing apparently healthy flowers and floral parts in fruit and causing gray mold during kiwifruit storage in Chile. Therefore, B. prunorum plays a secondary role in the epidemiology of gray mold developing in kiwifruit during cold storage.
Case Report: Effect of a Retinal Prosthesis System on Charles Bonnet Visual Hallucinations
Authors: Moore Vincent , Cantin Sylvie , Carignan Mathieu , Courchesne Marie , Qian Cynthia X. , Poncet Frédérique
Published: December 2020

SIGNIFICANCE

Charles Bonnet syndrome is commonly encountered and diagnosed in low-vision patients. It can be distressing for some of them, as there is no known effective treatment of this condition. Although there is a growing interest in retinal implants for blind patients with severe retinal diseases, the effect of these devices on Charles Bonnet syndrome visual hallucinations remains undocumented.

PURPOSE

The aim of this study was to report changes in the Charles Bonnet syndrome of a patient with retinitis pigmentosa after implantation of the Argus II retinal prosthesis.

CASE REPORT

A 65-year-old patient with retinitis pigmentosa and no light perception was frequently experiencing Charles Bonnet syndrome. In the hope of improving his vision, he received an Argus II retinal prosthesis in 2018 and participated in a 10-week rehabilitation program at the Institut Nazareth et Louis-Braille. The nature and the frequency of his Charles Bonnet syndrome were documented with the Questionnaire de repérage du syndrome de Charles Bonnet (a French questionnaire used to screen for Charles Bonnet syndrome) before the surgery and for 70 weeks after it. The patient's visual acuity and visual fields were monitored during the same period. Additional tests were administered to document the visual, psychological, and cognitive states of the patient throughout the study.

CONCLUSIONS

Although this case report confirmed that Argus II retinal prosthesis improves the performance of blind patients in visual tests, the improvement was not associated with a decrease in the symptoms of Charles Bonnet syndrome.
Case Report: Use of Prosthetic Replacement of the Ocular Surface Ecosystem Treatment of Traumatic Lid Ptosis in a Pediatric Patient
Authors: Phillis Kendra , Brocks Daniel , Carrasquillo Karen G.
Published: December 2020

SIGNIFICANCE

This report shares the long-term outcomes of an uncommon use of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment and scleral lenses in the treatment for patients with ptosis who are not surgical candidates.

PURPOSE

This study aimed to describe a case of pediatric traumatic lid ptosis and follow-up during an 8-year period with PROSE treatment.

CASE REPORT

A 7-year-old Honduran girl presented with a history of severe cranial, facial, and ocular trauma as a result of a motor vehicle accident. Significant ptosis with left-sided facial paralysis and irregular astigmatism significantly reduced the patient's visual function in the left eye. She was evaluated and treated with a scleral prosthetic device in the left eye to improve vision, the ocular surface, and overall function for activities of daily living. After 8 years of PROSE treatment, acuity in the left eye remained stable at 20/25. The corneal health remained stable throughout this period, without complications of corneal neovascularization or corneal edema.

CONCLUSIONS

Prosthetic replacement of the ocular surface ecosystem treatment provided support of the ocular surface and mechanical left upper eyelid lift in a traumatic eyelid ptosis, ultimately providing improved visual function during an extensive 8-year period in a pediatric patient. Further studies are needed to evaluate the applicability of this approach in broader ptosis cases.
Role of MRI in the Evaluation of Thoracoabdominal Emergencies
Authors: Ludwig Daniel R. , Raptis Constantine A. , Broncano Jordi , Bhalla Sanjeev , Luna Antonio
Published: December 2020

Thoracic and abdominal pathology are common in the emergency setting. Although computed tomography is preferred in many clinical situations, magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) have emerged as powerful techniques that often play a complementary role to computed tomography or may have a primary role in selected patient populations in which radiation is of specific concern or intravenous iodinated contrast is contraindicated. This review will highlight the role of MRI and MRA in the emergent imaging of thoracoabdominal pathology, specifically covering acute aortic pathology (acute aortic syndrome, aortic aneurysm, and aortitis), pulmonary embolism, gastrointestinal conditions such as appendicitis and Crohn disease, pancreatic and hepatobiliary disease (pancreatitis, choledocholithiasis, cholecystitis, and liver abscess), and genitourinary pathology (urolithiasis and pyelonephritis). In each section, we will highlight the specific role for MRI, discuss basic imaging protocols, and illustrate the MRI features of commonly encountered thoracoabdominal pathology.
Gram-negative bacilli bacteremia: a 7 year retrospective study in a referral Brazilian tertiary-care teaching hospital
Authors: Quillici Maria Clara Bisaio , Resende Daiane Silva , Gonçalves Iara Rossi , Royer Sabrina , Sabino Sebastiana Silva , Almeida Vitelhe Ferreira de , Ribas Rosineide Marques , Gontijo Filho Paulo Pinto
Published: December 2020

Introduction. Bloodstream infection is one of the most frequent and challenging hospital-acquired infections and it is associated with high morbidity, mortality and additional use of healthcare resources.

Hypothesis/Gap Statement: Bloodstream infections have consequences for the patient, such as the evolution to mortality and inappropriate empirical antibiotic prescription, especially when caused by multidrug-resistant Gram-negative bacilli.

Objective. To assess the impact of bloodstream infection and the status of multidrug resistance (MDR) in the evolution of patients who received inappropriate initial antibiotic therapy.

Methods. A retrospective surveillance was conducted on nosocomial bloodstream infections caused by Gram-negative bacilli (GNB) from January 2012 to December 2018 in an adult intensive care unit of a Brazilian tertiary teaching hospital.

Results. We identified 270 patients with GNB nosocomial bacteremia. Non-survivors were older (with an average age of 58.8 years vs 46.9 years, P=<0.0001), presented more severe illnesses, were immunosuppressed (73.7 vs 37.6%, P=<0.0001), were more likely to have septic shock (55.8 vs 22.4%, P=<0.0001) and had an increased usage of mechanical ventilators (98.6 vs 89.6%, P=0.0013) than survivors. In a logistic regression model, inappropriate empirical antibiotic therapy was not an independent predictor of mortality, different from mechanical ventilator (P=<0.0001; OR=28.0; 95% CI=6.3–123.6), septic shock (P=0.0051; OR=2.5; 95% CI=1.3–4.9) and immunosuppression (P=0.0066; OR=2.6; 95% CI=1.3–5.2). In contrast, in a separate model, MDR was strongly associated with the prescription of inappropriate initial antibiotic therapy (P=0.0030; OR=5.3; 95% CI=1.7–16.1). The main isolated pathogens were

Acinetobacter baumannii

(23.6 %) and

Klebsiella pneumoniae

(18.7 %). The frequency of MDR organisms was high (63.7 %), especially among non-fermenting bacilli (60.9 %), highlighting

A. baumannii

(81.6 %) and

Pseudomonas aeruginosa

(41.8 %).

Conclusion. Illness severity (septic shock and immunosuppression) and mechanical ventilation were identified as predictors of mortality. Additionally, MDR was a major determinant of inappropriate antibiotic empirical therapy, but not associated with mortality, and both characteristics were not statistically associated with death.
Stenotrophomonas maltophilia phenotypic and genotypic features through 4-year cystic fibrosis lung colonization
Authors: Alcaraz Eliana , Centrón Daniela , Camicia Gabriela , Quiroga María Paula , Di Conza José , Passerini de Rossi Beatriz
Published: December 2020

Introduction.Stenotrophomonas maltophiliahas emerged as one of the most common multi-drug-resistant pathogens isolated from people with cystic fibrosis (CF). However, its adaptation over time to CF lungs has not been fully established.

Hypothesis.Sequential isolates ofS. maltophiliafrom a Brazilian adult patient are clonally related and show a pattern of adaptation by loss of virulence factors.

Aim.To investigate antimicrobial susceptibility, clonal relatedness, mutation frequency, quorum sensing (QS) and selected virulence factors in sequentialS. maltophiliaisolates from a Brazilian adult patient attending a CF referral centre in Buenos Aires, Argentina, between May 2014 and May 2018.

Methodology.The antibiotic resistance of 11 S.maltophiliaisolates recovered from expectorations of an adult female with CF was determined. Clonal relatedness, mutation frequency, QS variants (RpfC–RpfF), QS autoinducer (DSF) and virulence factors were investigated in eight viable isolates.

Results.SevenS. maltophiliaisolates were resistant to trimethoprim–sulfamethoxazole and five to levofloxacin. All isolates were susceptible to minocycline. Strong, weak and normomutators were detected, with a tendency to decreased mutation rate over time.XbaIPFGE revealed that seven isolates belong to two related clones. All isolates were RpfC–RpfF1 variants and DSF producers. Only two isolates produced weak biofilms, but none displayed swimming or twitching motility. Four isolates showed proteolytic activity and amplifiedstmPr1andstmPr2genes. Only the first three isolates were siderophore producers. Four isolates showed high resistance to oxidative stress, while the last four showed moderate resistance.

Conclusion.The present study shows the long-time persistence of two relatedS. maltophiliaclones in an adult female with CF. During the adaptation of the prevalent clones to the CF lungs over time, we identified a gradual loss of virulence factors that could be associated with the high amounts of DSF produced by the evolved isolates. Further, a decreased mutation rate was observed in the late isolates. The role of all these adaptations over time remains to be elucidated from a clinical perspective, probably focusing on the damage they can cause to CF lungs.
Recombinant Fc-fusion vaccine of RBD induced protection against SARS-CoV-2 in non-human primate and mice
Authors: Sun Shihui , He Lei , Zhao Zhongpeng , Gu Hongjing , Fang Xin , Wang Tiecheng , Yang Xiaolan , Chen Shaolong , Deng Yongqiang , Li Jiangfan , Zhao Jian , Li Liang , Li Xinwang , He Peng , Li Ge , Li Hao , Zhao Yuee , Gao Chunrun , Lang Xiaolin , Wang Xin , Fei Guoqiang , Li Yan , Geng Shusheng , Gao Yuwei , Wei Wenjin , Hu Zhongyu , Han Gencheng , Sun Yansong
Published: December 2020

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to infect people globally. The increased COVID-19 cases and no licensed vaccines highlight the need to develop safe and effective vaccines against SARS-CoV-2 infection. Multiple vaccines candidates are under pre-clinical or clinical trails with different strengths and weaknesses. Here we developed a pilot scale production of a recombinant subunit vaccine (RBD-Fc Vacc) with the Receptor Binding Domain of SARS-CoV-2 S protein fused with the Fc domain of human IgG1. RBD-Fc Vacc induced SARS-CoV-2 specific neutralizing antibodies in non-human primates and human ACE2 transgenic mice. The antibodies induced in macaca fascicularis neutralized three divergent SARS-CoV2 strains, suggesting a broader neutralizing ability. Three times immunizations protected Macaca fascicularis (20ug or 40ug per dose) and mice (10ug or 20ug per dose) from SARS-CoV-2 infection respectively. These data support clinical development of SARS-CoV-2 vaccines for humans. RBD-Fc Vacc is currently being assessed in randomized controlled phase 1/II human clinical trails.

This study confirms protective efficacy of a SARS-CoV-2 RBD-Fc subunit vaccine.
GAPIT Version 3: Boosting Power and Accuracy for Genomic Association and Prediction
Authors: Wang Jiabo , Zhang Zhiwu
Published: December 2020

Genome-Wide Association Study (GWAS) and Genomic Prediction/Selection (GP/GS) are the two essential enterprises in genomic research. Due to the great magnitude and complexity of genomic data, analytical methods and their associated software packages are frequently advanced. GAPIT is a widely used Genomic Association and Prediction Integrated Tool. The first version was released to the public in 2012 with the implementation of the general linear model (GLM), mixed linear model (MLM), compressed MLM, and genomic Best Linear Unbiased Prediction (gBLUP). The second version was released in 2016 with several new implementations, including Enriched Compressed MLM and Settlement of mixed linear models Under Progressively Exclusive Relationship (SUPER). All the GWAS methods are based on the single locus test. For the first time, in the current release of GAPIT, version 3 implemented three multiple loci test methods, including Multiple Loci Mixed Model (MLMM), Fixed and random model Circulating Probability Unification (FarmCPU), and Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK). Additionally, two GP/GS methods were implemented based on Compressed MLM, named compressed BLUP, and SUPER, named SUPER BLUP. These new implementations not only boost statistical power for GWAS and prediction accuracy for GP/GS, but also improve computing speed and increase the capacity to analyze big genomic data. Here, we document the current upgrade of GAPIT by describing the selection of the recently developed methods, their implementation, and potential impact. All documents, including source code, user manual, demo data, and tutorials, are freely available at the GAPIT website (http://zzlab.net/GAPIT).
Human cytomegalovirus infection changes the pattern of surface markers of small extracellular vesicles isolated from first trimester placental histocultures
Authors: Bergamelli Mathilde , Martin Hélène , Bénard Mélinda , Ausseil Jérôme , Mansuy Jean-Michel , Hurbain Ilse , Mouysset Maïlys , Groussolles Marion , Cartron Géraldine , Gac Yann Tanguy le , Moinard Nathalie , Suberbielle Elsa , Izopet Jacques , Tscherning Charlotte , Raposo Graça , Gonzalez-Dunia Daniel , D’Angelo Gisela , Malnou Cécile E.
Published: December 2020

Currently, research on the use of non-invasive biomarkers as diagnosis and prognosis tools during pathological pregnancies is in full development. Among these, placenta-derived small extracellular vesicles (sEVs) are considered as serious candidates, since their composition is modified during many pregnancy pathologies. Moreover, sEVs are found in maternal serum and can thus be easily purified from a simple blood sample. In this study, we describe the isolation of sEVs from a histoculture model of first trimester placental explants. Using bead-based multiplex cytometry and electron microscopy combined with biochemical approaches, we characterized these sEVs and defined their associated markers and ultrastructure. We next examined the consequences of infection by human cytomegalovirus on sEVs secretion and characteristics. We observed that infection led to increased levels of expression of several surface markers, without any impact on the secretion and integrity of sEVs. Our findings open the prospect for the identification of new predictive biomarkers for the severity and outcome of this congenital infection early during pregnancy, which are still sorely lacking.
Genomic diversity, population structure and accessory genome analysis ofPasteurella multocida: New Insights into host adaptation and disease specialization
Authors: Carhuaricra Dennis , Hurtado Raquel , Luna Luis , Rosadio Raúl , Wheeler Jane C. , Azevedo Vasco , Maturrano Lenin
Published: December 2020

Pasteurella multocidais a multi-host pathogen that infects a wide spectrum of domestic and wild animals including humans. Despite its impact on health and economics,P. multocidais considered an enigmatic pathogen and the genetic basis of its pathogenicity and host adaptation still remains unclear. Here we present a detailed genomic framework based on 336 whole-genome sequences ofP. multocidaisolates from different animal species and countries. Our data provide genomic support of the existence of two very divergent phylogroups (PmI and PmII), which present a barrier to homologous recombination suggesting genetic isolation. Additionally, atorCADoperon, which reduces TMAO (trimethylamineN-oxide) to produce energy during bacterial anaerobic respiration, is present only in PmI and can act as a hypothetical driver of niche segregation between phylogroups. The PmI phylogroup harbors strains that infect a wider range of hosts than PmII, and shows a highly diverse phylogeny and accessory genome. We identified nine clonal lineages for PmI, seven of which are associated with specific hosts or diseases and contain distinct accessory gene pools that can confer ecologically relevant phenotypes. We found differential presence of a trehalose metabolism operon in the bovine lineage associated with pneumonic pasteurellosis; while, citrate, L-arabinose, L-fucose, and D-allose operons are only present in avian lineages. These findings suggest that alternative metabolic pathways may facilitate the establishment ofP. multocidaduring host colonization in the early stages of infection promoting the adaptation ofP. multocidalineages to certain hosts.
Monomethyl branched-chain fatty acid mediates amino acid sensing by mTORC1
Authors: Zhu Mengnan , Teng Fukang , Li Na , Zhang Li , Shao Jing , Sun Haipeng , Zhu Huanhu
Published: December 2020

Animals have developed various nutrient-sensing mechanisms for survival under fluctuating environments. Although extensive cultured cell-based analyses have discovered diverse mediators of amino acid sensing by mTOR, studies using animal models to illustrate intestine-initiated amino acid sensing mechanisms under specific physiological conditions are lacking. Here we developed aCaenorhabditis elegansmodel to examine the impact of amino acid deficiency on development. We discovered a leucine-derived monomethyl branched-chain fatty acid, and downstream glycosphingolipid, that critically mediate overall amino acid sensing by intestinal and neuronal mTORC1 that, in turn, regulates postembryonic development partly by controlling protein translation and ribosomal biogenesis. Additional data suggest that a similar mechanism may be conserved in mammals. This study uncovers an unexpected amino acid sensing mechanism mediated by a lipid biosynthesis pathway.
Controlling Cellular Arrangements via Stretched Bioprinting
Authors: He Chuanjiang , Liu Mengxue , Jiang Deming , Qin Chunlian , Liang Tao , Wu Pan , Han Chunmao , Huang Liquan , Hsia K. Jimmy , Wang Ping
Published: December 2020

Bioprinting is a common method to replicate geometrical architecture of native tissues. However, it usually fails to modulate cellular arrangements, which is critical for the tissue’s functionality. To our knowledge, no method has successfully addressed this challenge. Here, we report a method of controlling cellular orientation during the bioprinting process by integrating a stretch process into a modified bioprinting frame. We demonstrate that the cellular orientation is a result of cells’ sensing and responding to the tensile stress, instead of shear stress or topographical patterns. Moreover, our method shows a potent capability to induce myoblast differentiation, fusion and maturation without the presence of differentiation medium. As a potential clinical application, we demonstrate that aligned myofibers directly printed onto injured muscle in vivo, can not only repair the structure of damaged tissue, but also recover the muscle functionalities effectively. This study shows that the new method can produce tissues with precise control of cellular arrangements and more clinically viable functionalities.

Significance Statement

Due to no method could reproduce the exact cellular arrangements of native tissues in engineered tissues, tissue engineering facing difficult in fabricating 3D tissues that possess desirable biological and mechanical functionalities for biomedical applications. For the first time, we report a method of controlling cellular orientation during 3D bio-printing process. This method can be used to produce engineered tissues with controlled cellular arrangement with several different cell types. Moreover, this method shows a potent capability of fabricating fully mature and aligned myofibersin vitroin the absence of differentiation medium. As potential clinical applications, with this method, engineered tissues could be directly printedin vivowith high efficacy of tissue repair and function recovery.
No change in oxytocin level before a human intergroup competition: study among Polish players before rugby and handball matches
Authors: Koziel Slawomir , Kociuba Marek , Ignasiak Zofia , Rokita Andrzej , Cichy Ireneusz , Dutkowski Andrzej , Ściślak Marcin , Kochan Katarzyna , Sebastjan Anna , Spinek Anna , Lorek Daria , Chakraborty Raja , Bogin Barry
Published: December 2020

Objectives

The aim of the present study was to assess the changes in urinary oxytocin concentration during the period between five days before, and on the day of match, among rugby and handball players.

Methods

The study used a repeated measures design with the relative oxytocin level as the outcome variable measured at two subsequent points of time, viz., on five days before as well as on the days of matches. Nine male rugby players with a mean age of 27.62 years (SD = 4.21) and 18 male handball players with a mean age of 17.03 years (SD = 0.57) participated. Urinary oxytocin level was measured by ELISA immunoassay as a ratio to the concentration of creatinine [mg/ml] measured through colorimetric detection. Differences in oxytocin level were assessed by ANOVA with repeated measurements.

Results

The OT/CRE levels significantly differed between the type of player (rugby or handball) but not between times of measurements. Tukey’s post-hoc tests revealed that significant differences were only between OT/CRE level in a day of match in rugby players and in 5 days before match in handball players (p<0.05).

Conclusion

There was no change in oxytocin levels during the time periods between five days before and on the day of a match, in either of the two kinds of players. The change in oxytocin might be traceable during the match but not before a match and thus perhaps depends on a more subtle context of competition, but not on the assumption of competition.
Association between the extent of DNA methylation at the CpG sites ofHIF3Aand parameters of obesity in the general Japanese population
Authors: Mizuno Genki , Yamada Hiroya , Munetsuna Eiji , Yamazaki Mirai , Ando Yoshitaka , Fujii Ryosuke , Tsuboi Yoshiki , Teshigawara Atsushi , Kageyama Itsuki , Osakabe Keisuke , Sugimoto Keiko , Ishikawa Hiroaki , Ichino Naohiro , Ohta Yoshiji , Ohashi Koji , Hashimoto Shuji , Suzuki Koji
Published: December 2020

Obesity is a major public health problem worldwide owing to the substantial increase in risk of metabolic diseases. Hypoxia-inducible factors (HIFs) regulate transcriptional responses to hypoxic stress. DNA methylation in the CpG sites of intron 1 ofHIF3Ais associated with body mass index in the whole blood and adipose tissue. This study investigates the correlation between DNA methylation ofHIF3Aand parameters of obesity, including thickness of visceral (VAT) and subcutaneous adipose tissues, in the general Japanese population. Participants (220 men and 253 women) who underwent medical examination were enrolled in this cross-sectional study. We used pyrosequencing to quantify DNA methylation (CpG sites of cg16672562, cg22891070, and cg27146050) inHIF3A. DNA methylation ofHIF3Awas only different in women. Multiple regression analysis showed that DNA methylation level at cg27146050 was associated with thickness of VAT in women. DNA methylation level at cg27146050 also correlated with body mass index and percentage of body fat in women after excluding smokers and non-smokers who quit smoking with the last 5 years. DNA methylation in the CpG site (cg27146050) ofHIF3Acorrelated with parameters of obesity in Japanese women.
Modeling the circadian regulation of the immune system: sexually dimorphic effects of shift work
Authors: Abo Stéphanie M.C. , Layton Anita T.
Published: December 2020

The circadian clock exerts significance influence on the immune system and disruption of circadian rhythms has been linked to inflammatory pathologies. shift workers often experience circadian misalignment as their irregular work schedules disrupt the natural sleep-wake cycle, which in turn can cause serious health problems associated with alterations in genetic expressions of clock genes. In particular, shift work is associated with impairment in immune function, and those alterations are sex-specific. The goal of this study is to better understand the mechanisms that explain the weakened immune system in shift workers. To achieve that goal, we have constructed a mathematical model of the mammalian pulmonary circadian clock coupled to an acute inflammation model. shift work was simulated by an 8h-phase advance of the circadian system with sex-specific modulation of clock genes. The model reproduces the clock gene expression in the lung and the immune response to various doses of lipopolysaccharide (LPS). Under normal conditions, our model predicts that a host is more sensitive to LPS at CT12 versus CT0 due to a change in the dynamics of IL-10. We identify REV-ERB as a key modulator of IL-10 activity throughout the circadian day. The model also predicts a reversal of the times of lowest and highest sensitivity to LPS, with males and females exhibiting an exaggerated response to LPS at circadian time (CT) 0, which is countered by a blunted immune response at CT12. Overall, females produce fewer pro-inflammatory cytokines than males, but the extent of sequelae experienced by males and females varies across the circadian day. This model can serve as an essential component in an integrative model that will yield mechanistic understanding of how shift work-mediated circadian disruptions affect the inflammatory and other physiological responses.

Author summary

Shift work has a negative impact on health and can lead to chronic diseases and illnesses. Under regular work schedules, rest is a night time activity and work a daytime activity. Shift work relies on irregular work schedules which disrupt the natural sleep-wake cycle. This can in turn disrupt our biological clock, called the circadian clock, a network of molecular interactions generating biochemical oscillations with a near 24-hour period. Clock genes regulate cytokines before and during infection and immune agents can also impact the clock function. We provide a mathematical model of the circadian clock in the lung coupled to an acute inflammation model to study how the disruptive effect of shift work manifests itself in males and females during inflammation. Our results show that the extent of sequelae experienced by male and female mice depends on the time of infection. The goal of this study is to provide a mechanistic insight of the dynamics involved in the interplay between these two systems.
Estimating disease spread using structured coalescent and birth-death models: A quantitative comparison
Authors: Seidel Sophie , Stadler Tanja , Vaughan Timothy G.
Published: December 2020

Understanding how disease transmission occurs between subpopulations is critically important for guiding disease control efforts irrespective of whether the subpopulations represent geographically separated people, age or risk groups. The structured coalescent (SC) and the multitype birth-death (MBD) model can both be used to infer migration rates between subpopulations from phylogenies reconstructed from pathogen genetic sequences. However, the two classes of phylodynamic methods rely on different assumptions.

Here, we report on a simulation study which compares inferences made using these models for a variety of migration rates in both endemic diseases and epidemic outbreaks. For the epidemic outbreak, we found that the MBD recovers the true migration rates better than the SC regardless of migration rate. We hypothesize that the inaccurate SC estimates stem from the its assumption of a constant population size. For the endemic scenario, our analysis shows that both models obtain a similar coverage of the migration rates, while the SC provides slightly narrower posterior intervals. Irrespective of the scenario, both models estimate the root location with similar coverage.

Our study provides concrete modelling advice for infectious disease analysts. For endemic disease either model can be used, while for epidemic outbreaks the MBD should be the model of choice. Additionally, our study reveals the need to develop the SC further such that varying population sizes can easily be taken into account.

Author summary

Controlling an infectious disease requires us to quantify and understand how it spreads through pools of susceptible individuals, defined by their belonging to different geographical regions, age or risk groups. Rates of pathogen movement between these pools can be inferred from pathogen phylogenies which are themselves reconstructed from pathogen genetic sequences collected from infected individuals. Two popular foundations for such models are the multitype birth-death model and the structured coalescent.

Although these models fulfill the same purpose, they differ in their assumptions and can, hence, produce contrasting results. To assess the appropriateness of the models in different situations, we performed a simulation study. We find that, for endemic diseases, both models are able to estimate the migration parameters reliably. For epidemic outbreaks, however, the multitype birth-death model obtains better estimates of the migration rates. We hypothesize that the structured coalescent’s inaccurate estimates for the epidemic scenario arise because it assumes a constant number of infected individuals through time.
First computational design of Covid-19 coronavirus vaccine using lambda superstrings
Authors: Martínez Luis , Malaina Iker , Salcines David , Terán Héctor , Alegre Santos , De la Fuente I.M. , Lopez Elena Gonzalez , Vinyals Gonzalo Ocejo , Álvarez Carmen
Published: December 2020

In this work we have developed, by employing lambda superstrings, a map of candidate vaccines against SARS-CoV-2 with lengths between 9 and 200, based on estimations of the immunogenicity of the epitopes and the binding affinity of epitopes to MHC class I molecules using tools from the IEDB Analysis Resource, as well as the overall predictions obtained using the VaxiJen tool. We have synthesized one of the peptides, specifically the one of length 22, and we have carried out an immunogenicity assay and a cytokine assay, which has given positive results in both cases.
Remodeling and activation mechanisms of outer arm dyneins revealed by cryo-EM
Authors: Kubo Shintaroh , Yang Shun Kai , Black Corbin , Dai Daniel , Valente Melissa , Gaertig Jacek , Ichikawa Muneyoshi , Bui Khanh Huy
Published: December 2020

Cilia are thin microtubule-based protrusions of eukaryotic cells. The swimming of ciliated protists and sperm cells is propelled by the beating of cilia. Cilia propagate the flow of mucus in the trachea and protect the human body from viral infections. The main force generators of ciliary beating are the outer dynein arms (ODAs) which attach to the doublet microtubules. The bending of cilia is driven by the ODAs’ conformational changes caused by ATP hydrolysis. Here, we report the native ODA complex structure attaching to the doublet microtubule by cryoelectron microscopy. The structure reveals how the ODA complex is attached to the doublet microtubule via the docking complex in its native state. Combined with molecular dynamics simulations, we present a model of how the attachment of the ODA to the doublet microtubule induces remodeling and activation of the ODA complex.
The interactome of the N-terminus of band 3 regulates red blood cell metabolism and storage quality
Authors: Issaian Aaron , Hay Ariel , Dzieciatkowska Monika , Roberti Domenico , Perrotta Silverio , Darula Zsuzsanna , Redzic Jasmina , Busch Micheal P. , Page Grier P. , Hansen Kirk C. , Eisenmesser Elan Z , Zimring James C , D’Alessandro Angelo
Published: December 2020

Band 3 (anion exchanger 1 - AE1) is the most abundant membrane protein in red blood cells (RBCs), the most abundant cell in the human body. A compelling model, based on indirect evidence, posits that - at high oxygen saturation - the N-term cytosolic domain of AE1 binds to and inhibits glycolytic enzymes, thus diverting metabolic fluxes to the pentose phosphate pathway to generate reducing equivalents. Dysfunction of this mechanism occurs during RBC aging or storage under blood bank conditions, suggesting a role for AE1 in the regulation of blood storage quality and efficacy of transfusion – a life-saving intervention for millions of recipients worldwide. Here we leverage two murine models carrying genetic ablations of AE1 to provide the first direct mechanistic evidence of its role in metabolic regulation and blood storage quality. Observations in mice phenocopied those in a human subject lacking expression of AE11-11(band 3Neapolis),while common polymorphisms in the region coding for AE11-56increased susceptibility to osmotic hemolysis in healthy blood donors. Through thermal proteome profiling and cross-linking proteomics, we provide the first comprehensive analysis of the RBC interactome, with a focus on AE11-56and validate recombinant AE1 interactions with glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Finally, we show that incubation with a cell-penetrating AE11-56peptide can rescue the metabolic defect in glutathione recycling and boost post-transfusion recoveries of stored RBCs from healthy human donors and genetically ablated mice, paving the way for the in vivo metabolic manipulation of RBCs facing oxidant stress – a landmark of many diseases.

Key points

Genetic ablation of N-term of band 3 results in significant metabolic aberrations and poor post-transfusion recoveries in mice and humans;

Structural studies on the N-term of band 3 reveal a complex interactome with several enzymes, including GAPDH;
Stresses in the metastatic cascade: molecular mechanisms and therapeutic opportunities
Authors: Shen Minhong , Kang Yibin
Published: December 2020

Metastasis is the ultimate “survival of the fittest” test for cancer cells, as only a small fraction of disseminated tumor cells can overcome the numerous hurdles they encounter during the transition from the site of origin to a distinctly different distant organ in the face of immune and therapeutic attacks and various other stresses. During cancer progression, tumor cells develop a variety of mechanisms to cope with the stresses they encounter, and acquire the ability to form metastases. Restraining these stress-releasing pathways could serve as potentially effective strategies to prevent or reduce metastasis and improve the survival of cancer patients. Here, we provide an overview of the tumor-intrinsic, microenvironment- and treatment-induced stresses that tumor cells encounter in the metastatic cascade and the molecular pathways they develop to relieve these stresses. We also summarize the preclinical and clinical studies that evaluate the potential therapeutic benefit of targeting these stress-relieving pathways.
A new role for the synaptonemal complex in the regulation of meiotic recombination
Authors: Hollingsworth Nancy M.
Published: December 2020

Proper segregation during meiosis requires that homologs be connected by the combination of crossovers and sister chromatid cohesion. To generate crossovers, numerous double-strand breaks (DSBs) are introduced throughout the genome by the conserved Spo11 endonuclease. DSB formation and its repair are then highly regulated to ensure that homologous chromosomes contain at least one crossover and no DSBs remain prior to meiosis I segregation. The synaptonemal complex (SC) is a meiosis-specific structure formed between homologous chromosomes during prophase that promotes DSB formation and biases repair of DSBs to homologs over sister chromatids. Synapsis occurs when a particular recombination pathway is successful in establishing stable interhomolog connections. In this issue of Genes & Development, Mu and colleagues (pp. 1605–1618) show that SC formation between individual chromosomes provides the feedback to down-regulate Spo11 activity, thereby revealing an additional function for the SC.
Teaching, virtually: a critical reflection
Authors: Powell Lisa , McGuigan Nicholas
Published: December 2020

Purpose

The purpose of this paper is to present critical educator reflections on the pivot from the traditional physical accounting classroom to the virtual learning environment amidst COVID-19 pandemic lockdowns.

Design/methodology/approach

This paper outlines the reflexive experiences of two accounting educators on their scholarly journey into virtual learning and their inhabiting of the virtual accounting classroom. We adopt a critical stance in exploring what has been lost and insights gained.

Findings

We heed caution in the ongoing reliance on digital technologies and virtual learning that strip accounting education of its richness and complexity. Although the virtual learning environment brings with it benefits of accessibility and flexibility, it fails to replace the complexity of human connection, authenticity and informal spontaneity found in face-to-face learning. We further contend that COVID-19 presents an opportunity to rethink accounting education. We encourage educators to embrace this opportunity as a force for educational transformation; to reimagine an accounting education that embraces change, ambiguity and humanistic qualities such as empathy, compassion and humility.

Originality/value

Our critical educator reflections explore the impact of COVID-19 on the humanistic qualities at the heart of education and on the future of accounting education. This paper contributes to the scholarship of teaching and learning during global pandemics and other crises.
Achieving food security through live animal imports in the Gulf Cooperation Council countries
Authors: Gani Azmat
Published: December 2020

Purpose

This article examines the main factors that drive live animal imports in the Gulf Cooperation Council (GCC) countries in the Middle East.

Design/methodology/approach

The analysis is based on a gravity model framework, and it incorporates annual data for imports of cattle, sheep and goats during the period 2004–2017 for six countries. The panel estimation technique is employed to disentangle the drivers of the GCC live animal imports.

Findings

The results reveal that imports of live animals are consistently positive and statistically significantly correlated with the economic sizes of importer countries, liner shipping connectivity (LSC) (for cattle and goats) and culture (for cattle and sheep). Other determinants include falling tariffs for live cattle imports and falling costs of doing business for live sheep imports. Distance is found to exert statistically significant friction for imports of live goats.

Practical implications

The GCC countries offer substantial opportunities for livestock trade to fulfil the growing demand for meat as a dietary requirement. Countries aiming at the GCC live animal segment of agricultural business would have to ensure reliable access to maritime transport connectivity and better understanding and insights into the business environment, transport logistics, trade policies, economic strength and cultural connections with meat consumption. The food-related supply chain system ought to have an extensive awareness of variables as the findings of this study revealed that can impact exchanges encountered across the supply chains.

Originality/value

Until now, no study has empirically investigated the effect of live animal imports within a coherent trade theoretical framework in the GCC. The novelty of this research is that it makes the first attempt to identify the factors driving the extensive GCC live animal imports for meat consumption with a specific geographical focus. This study also complements the existing sparse empirical literature on trade-in live animals.
The impact of temporary workers on the conversion of innovation efforts into product innovations: the case of Spanish companies
Authors: Rodríguez-Ruiz Óscar , Fernández-Menéndez José , Díaz-Martínez Zuleyka , Fossas-Olalla Marta
Published: December 2020

Purpose

In this paper, we study the influence of temporary workers in the relationship between innovation effort and product innovation in a large sample of Spanish manufacturing firms in a six-year period.

Design/methodology/approach

The article uses a zero-inflated regression model to analyse how the performance of innovation efforts is affected by the impact of temporary employment.

Findings

Our results show that the use of temporary employment has adverse effects for the conversion of innovation investments into innovation outputs. Firms with higher levels of fixed-term workers have less product innovations in comparison to firms that do not use this kind of workforce. However, this negative impact is less detrimental in technological-intensive sectors.

Originality/value

The value of this research for employment relations is salient as workers long-term protection seems to enhance the effectiveness of the innovation process. At the same time, the effects of temporary work vary depending on the sector.
The “stay at home” orders effect on mental health of Egyptian adults during the COVID-19 pandemic partial lockdown
Authors: Saleh Mai Sabry
Published: December 2020

Purpose

Mental health is one of the aspects seriously affected by the COVID-19 pandemic. Governmental preventive measures worldwide disturbed people’s daily routine, social activities, access to education and even impacted their working environment. The present work aims at screening the expected negative effects on mental and psychological wellbeing.

Design/methodology/approach

An online survey was introduced through an internet-based platform to assess mental wellbeing (MW) and stress among Egyptian adults using SHORT Warwick-Edinburgh Mental Wellbeing Scale and Falsification of Type Scale, respectively. Socio-demographics were also collected. Data from 150 respondents through the period from May 25 till June 1 were tabulated and statistical analyses were performed.

Findings

More than 70% of respondents declared jobs being affected by the pandemic. Females showed deteriorated state of mental health, together with the youth (≤44 years) and those who lost their jobs or suffered reduced income. In conclusion, mental health as expressed by MW and stress showed to be affected among the Egyptian adults due to the “stay at home” orders. Prompt actions are highly recommended to save vulnerable populations at the time being and from the aggravation of their mental problems in the long term.

Originality/value

The study is the first in Egypt figuring out affected populations and vulnerable categories that need extra care in the future. It provides valuable data and expresses reasonable explanations to the obtained findings. The study also introduces recommendations and highlights hot topics for future research.