bluuebunny/crossref_metadata_2025 huggingface dataset:
Prior Use of Medication for Primary Prevention in Patients with Coronary Syndrome
Authors: Gaviria-Mendoza Andrés , Zapata-Carmona Julián Andrés , Restrepo-Bastidas Andrés Alirio , Betancur-Pulgarín Carmen Luisa , Machado-Alba Jorge Enrique
Published: August 2020

Background: Cardiovascular disease, especially coronary disease, represents one of the main causes of morbidity and mortality. Objective: To determine the drug prescription profile for primary cardiovascular prevention prior to a first acute coronary syndrome event. Methods: Cross-sectional study. We included adult patients of any sex affiliated with one healthcare insurer of the Colombian Health System, with a diagnosis of a first episode of acute coronary syndrome that occurred during the period of 2015 to 2016. Sociodemographic, clinical and pharmacological variables were evaluated from clinical records. The cardiovascular risk score prior to the event was calculated, and the need for the use of statins and aspirin in primary prevention was defined according to the recommendations of clinical practice guidelines. Results: Clinical records of 322 patients were reviewed with mean age of 61.9 ± 10.8 years, and 77.3% were men. The most frequent comorbidities were dyslipidemia (64.3%), arterial hypertension (62.7%) and diabetes mellitus (30.1%); 22% of the patients were obese, and 33.5% were smokers. The cardiovascular risk score was calculated in 211 patients (65.5%) who had the necessary variables complete. The median 10-year risk according to Framingham risk score was 21.4%, and it was 16.3% according to the American Heart Association. From the 211 patients with risk scores, there were 179 (84.8%) who needed statins (175 of high intensity, 97.8%), and 88 (27.3%) required aspirin as a primary prevention; however, 56 of these patients (31.3%) did not receive any statins, 127 (72.6%) did not receive the high intensity statin they needed, and 38 (43.2% of those with indication) lacked aspirin. Conclusion: Real-life data show that among a group of patients with high cardiovascular risk, a substantial proportion were not receiving medications for primary prevention necessary to reduce their risk and finally suffered an acute coronary event.
Seated Lateral X-ray Is a Better Stress Radiograph of the Lumbar Spine Compared to Standing Flexion
Authors: Sielatycki J. Alex , Metcalf Tyler , Koscielski Marissa , Devin Clinton J. , Hodges Scott
Published: August 2020

Study Design:

Prospective lumbar radiograph analysis.

Objective:

To compare changes in lumbar lordosis in standing flexion versus seated lateral radiographs.

Methods:

Standing lateral, standing flexion, and seated lateral X-rays of the lumbar spine were obtained in patients presenting with low back pain. Trauma, tumor, and revision cases were excluded. Changes in global lumbar as well as segmental lordosis were measured in each position.

Results:

Seventy adult patients were reviewed. Overall, the greatest changes in lordosis were seen at L4-S1 in both the seated and flexion X-rays (12.5° and 6.3°, respectively). Greater kyphosis was seen in seated versus flexion X-rays (21.6° vs 15.8°); changes in lordosis from L1-L3 were similar in both positions, with little change seen at these levels (approximately 5° to 7°). On subgroup analysis, these differences were magnified in analyzing only patients that moved at least 20° globally, and there were no significant differences between sitting and flexion in “stiff” patients that moved less than 20° globally.

Conclusion:

Greater lumbar kyphosis was seen in the seated position compared to standing flexion, especially from L4-S1. Given these results we suggest the use of seated lateral X-rays to dynamically assess the lumbar spine. These findings may also guide future research into the mechanism and clinical relevance of a stiff versus mobile lumbar spine, as well as into the sensitivity of seated X-rays in detecting instability.
Iatrogenic Delayed Pneumothorax After Transbronchial Biopsy
Authors: Rajdev Kartikeya , Herring Dustin N. , Lahan Shubham , Wilson Kyle , Murphy Peter J.
Published: August 2020

Transbronchial biopsy (TBB) is one of the commonly performed procedures by pulmonologists in everyday practice. Although the procedure has a very low-risk profile, complications often develop in certain patients. Pneumothorax is one such complication pertaining to TBB. As only a small percent of procedures get complicated by pneumothorax, handful of cases have been reported with its delayed occurrence in the past 5 decades. The purpose of our report is to highlight another uncommon yet interesting case of delayed iatrogenic pneumothorax in an immunocompromised patient after TBB. Although the chain of events behind the pathophysiology of delayed pneumothorax largely remain a mystery, its development has been linked to altered immune mechanics as they are frequently recognized in immunocompromised patients.
China’s Balancing Behaviour Against the United States and the Special Importance of Myanmar
Authors: Mannan Md Abdul
Published: August 2020

As China rises, Sino–US competition for influence in East and Southeast Asia has become inescapable. China’s growing influence on its south-western neighbour, Myanmar, is a case in point. The impact of China’s rise is more strongly felt, politically and economically, in Myanmar than elsewhere in the world. This article asks the follow question: What explains China’s more aggressive political and economic clout in Myanmar than elsewhere in the world? To answer this question, this article argues that Myanmar holds a unique importance to China’s balancing act against the preponderance of American power in a unipolar world. Most of the available literature on China’s inroads into Myanmar focus on China’s geopolitical and strategic interests. With such focus, existing literatures take on Myanmar’s importance to China in terms of China’s politics of resource extraction that meets the requirement of its overall economic development. There is no denying it—resource extraction is important for China in order to feed its expanding economy. But hardly any study frames Myanmar’s special weight in China’s politics of resource extraction from the perspective of Beijing’s balancing act against the United States (US). China’s balancing act is characterized by an ‘economic prebalancing’ strategy. The strategy is rooted in China’s grand strategy of acquiring ‘comprehensive national strength’, and more precisely, it is embedded in Beijing’s ‘peaceful development’ strategy. The article asserts that Myanmar is critically important in China’s economic prebalancing strategy against the United States.
Belts and roads every- and nowhere: Conceptualizing infrastructural corridorization in the Indian Ocean
Authors: Alff Henryk
Published: August 2020

This article scrutinizes the Maritime Silk Road Initiative by framing it not as a static, state-centric device to channel Chinese developmental ambitions, but by emphasizing the flexible character of its production and the provisional configuration of its materialization. It draws on assemblage theory as a conceptual angle to, on the one hand, focus on the agentive character of human and non-human ‘actors’ such as ‘traveling’ discourses of development or infrastructures to explore Maritime Silk Road Initiative’s materialization ‘on the ground’ in its emergent rather than resultant way, on the other.
How “wild” are hatchery salmon? Conservation policy and the contested framing of nature in Canada and the United States
Authors: Berseth Valerie , Matthews Ralph
Published: August 2020

The idea of the Anthropocene presents a paradox for conservation: to restore and protect wild species and ecosystems, greater human intervention is required through efforts such as artificial propagation. This paradox is evident in efforts to conserve Pacific salmon. Salmon hatcheries produce millions of salmon to augment wild populations and sustain fishing industries, but emerging knowledge about salmon genomics has called into question the “wildness” of hatchery salmon. This article examines how the scientific uncertainties regarding wild species are contested by a range of stakeholders and how particular frames become concretized in policy frameworks. Despite the significance of laws and policies to the governance of such hybrid species, they have received limited attention. Drawing on archival documents, legislation, policies, government reports, and media sources, we conduct a cross-national comparative analysis of how wildness is framed in policy debates in Canada and the United States. We find that hatchery-born salmon occupy a position at the threshold of scientific and cultural definitions of wildness and this ambiguity facilitates political contests among groups with divergent interests in conservation and views of the human–nature relationship. As a result, hatchery salmon have been regulated differently across time and geographic and jurisdictional space. These findings contribute to an expanding literature on conservation in the Anthropocene and managing wild species.
Sex-Specific Programming of Cardiac DNA Methylation by Developmental Phthalate Exposure
Authors: Svoboda Laurie K , Wang Kai , Cavalcante Raymond G , Neier Kari , Colacino Justin A , Sartor Maureen A , Dolinoy Dana C
Published: August 2020

Phthalate plasticizers are ubiquitous chemicals linked to several cardiovascular diseases in animal models and humans. Despite this, the mechanisms by which phthalate exposures cause adverse cardiac health outcomes are unclear. In particular, whether phthalate exposures during pregnancy interfere with normal developmental programming of the cardiovascular system, and the resulting implications this may have for long-term disease risk, are unknown. Recent studies suggest that the effects of phthalates on metabolic and neurobehavioral outcomes are sex-specific. However, the influence of sex on cardiac susceptibility to phthalate exposures has not been investigated. One mechanism by which developmental exposures may influence long-term health is through altered programming of DNA methylation. In this work, we utilized an established mouse model of human-relevant perinatal exposure and enhanced reduced representation bisulfite sequencing to investigate the long-term effects of diethylhexyl phthalate (DEHP) exposure on DNA methylation in the hearts of adult male and female offspring at 5 months of age (n = 5-7 mice per sex and exposure). Perinatal DEHP exposure led to hundreds of sex-specific, differentially methylated cytosines (DMCs) and differentially methylated regions (DMRs) in the heart. Pathway analysis of DMCs revealed enrichment for several pathways in females, including insulin signaling, regulation of histone methylation, and tyrosine phosphatase activity. In males, DMCs were enriched for glucose transport, energy generation, and developmental programs. Notably, many sex-specific genes differentially methylated with DEHP exposure in our mouse model were also differentially methylated in published data of heart tissues collected from human heart failure patients. Together, these data highlight the potential role for DNA methylation in DEHP-induced cardiac effects and emphasize the importance of sex as a biological variable in environmental health studies.
An Understudied Dimension: Why Age Needs to Be Considered When Studying Epigenetic-Environment Interactions
Authors: Barrere-Cain Rio , Allard Patrick
Published: August 2020

We live in a complex chemical environment where there are an estimated 350 000 chemical compounds or mixtures commercially produced. A strong body of literature shows that there are time points during early development when an organism’s epigenome is particularly sensitive to chemicals in its environment. What is less understood is how gene-environment and epigenetic-environment interactions change with age. This question is bidirectional: (1) how do chemicals in the environment affect the aging process and (2) how does aging affect an organism’s response to its chemical environment? The study of gene-environment interactions with age is especially important because, in many parts of the world, older individuals are a large and rapidly growing proportion of the population and because aging is a process universal to most of the animal kingdom. Epigenetics has emerged as a crucial framework for studying aging as epigenetic pathways, often triggered by environmental stimuli, have been shown to be essential regulators of the aging process. In this perspective article, we delineate the connection between aging, epigenetics, and environmental exposures. We discuss why it is essential to consider age when researching how an organism interacts with its environment. We describe recent advances in understanding how the chemical environment affects aging and the gap in research on how age affects an organism’s response to the environment. Finally, we highlight how model organisms and network approaches can help fill this crucial gap. Taken together, systemic changes that occur in the epigenome with age indicate that adult organisms cannot be treated as a homogeneous population and that there are discrete mechanisms modulating the aging epigenome that we do not yet understand.
A comparative study of morphological characteristics of medium-density fiberboard dust by sieve and image analyses
Authors: Ding Tao , Zhao Jiafeng , Zhu Nanfeng , Wang Chengming
Published: August 2020

Sanding dust is the main source of dust emission during the manufacturing process of medium-density fiberboard (MDF), and particle size and shape characteristics are the fundamental properties influencing its environmental influence and handling behaviors. However, there are few deep and comprehensive researches on the morphology of MDF sanding dust. In this study, the morphological characteristics of MDF sanding dust were explored by sieve and image analyses. It was found that more than 95% of MDF sanding dust was inhalable particles smaller than 100 μm, which poses a considerable potential risk to human health and safety, especially with the presence of other chemical constituents. The particle size span of MDF dust was relatively wide though the particle surface texture was quite uniform. The particle geometric proportion represented by aspect ratio decreased markedly with the reduction of particle size. The larger particles presented typical anisotropic structure, while the smaller ones showed homogeneous appearance, indicating quite complex handling behaviors. In addition, image analysis was found to provide a better insight into the morphological characteristics of MDF sanding dust compared to sieve analysis, and could be a promising dust morphology evaluation technology.
Melanocortin-4 receptor (MC4R) rs17782313 polymorphism interacts with Dietary Approach to Stop Hypertension (DASH) and Mediterranean Dietary Score (MDS) to affect hypothalamic hormones and cardio-metabolic risk factors among obese individuals
Authors: Khodarahmi Mahdieh , Jafarabadi Mohammad Asghari , Farhangi Mahdieh Abbasalizad
Published: August 2020

Background and aim

The association with obesity of a common variant near the melanocortin-4 receptor (MC4R) gene (rs17782313) has been indicated in various studies. Adherence to dietary quality indices also have shown to have potential favorable effects on obesity-related health outcomes. However, no study has examined the interaction between rs17782313 and the Dietary Approach to Stop Hypertension (DASH) score and the Mediterranean Dietary Score (MDS) on cardio-metabolic risk factors and hypothalamic hormones. Therefore, the purpose of the current study was to examine whether adherence to these dietary quality indices modifies the association of the MC4R rs17782313 polymorphism with cardio-metabolic risk factors and hypothalamic hormones among obese adults.

Method

Two hundred eighty-eight healthy obese adults were recruited in this cross-sectional study. Diet quality indices, including DASH score and MDS, were calculated from a validated 147-item food frequency questionnaire (FFQ). MC4R s17782313 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An ANCOVA multivariate interaction model was used to assess the gene-diet interaction.

Results

Significant interactions were detected between DASH score and MC4R rs17782313 genotypes on systolic blood pressure (SBP), atherogenic index of plasma (AIP), and serum glucose and triglyceride (TG) among the female group (pInteraction< 0.05). In the male group, there were gene-DASH and gene-MDS interactions in relation to serum glucose concentration and plasma α-melanocyte stimulating hormone (MSH) levels, but these were found only in multi-adjusted interaction models (pInteraction< 0.05). In addition, there was a significant interaction between MC4R rs17782313 polymorphism and DASH score on plasma agouti-related peptide (AgRP) concentrations in the female group in a multivariate interaction model (pInteraction< 0.05). An inverse association between DASH score and chance of having the CC genotype in a multivariate-adjusted model among women was also revealed.

Conclusion

MC4R rs17782313 interacts with healthy dietary pattern (DASH score and MDS) to influence cardio-metabolic risk factors and hypothalamic hormones in obese individuals. Prospective cohort studies are needed to further assess these findings.
Experience of a tertiary-level urology center in the clinical urological events of rare and very rare incidence. III. Psychourological events: 2. Phobia of renal failure due to loin pain
Authors: Gadelkareem Rabea Ahmed , Azoz Nashwa Mostafa , Reda Ahmed , Shahat Ahmed Abdelhamid , Abdelhafez Mohamed Farouk , Faddan Amr Abou , Farouk Mahmoud , Fawzy Mohamed , Osman Mahmoud Mohammed , Elgammal Mohammed Abdallah
Published: August 2020

Background

End-stage renal disease and loin pain are prevalent nephrourological topics with unfavorable reputations among populations. We aimed to present our center’s experience with the cases of phobia of renal failure in relation to loin pain.

Methods

It is a retrospective study of phobia of renal failure among the patients who presented with loin pain to our center between July 1991 and June 2017. Description of perception of renal failure risk was guided by the modified Common Sense Model of Illness Representation.

Results

Of more than 64, 000 patients who presented with loin pain, only 78 patients (0.12%) had phobia of renal failure. Mean age ± SD (Range) was 41.12 ± 9.58 (23–60) years. Sixty-four patients (82.1%) expressed directly fear of renal failure. Physical examination and investigations revealed no risks of renal failure in all patients. High percentages of phobia of renal failure were associated with the female gender (73.1%), the presence of a relative patient with renal failure (83.3%), and low socioeconomic levels: education (89.7%), residential (75.6%), and economic status (88.5%) levels. The modified Common Sense Model of Illness Representation revealed predominant emotional representations and unreal cognitive domains with altered perception of renal failure risk.

Conclusions

Phobia of renal failure is very rare. It is a consequence of the altered perception of risk of renal failure due to unconscious attribution of loin pain to renal failure. Female gender, the presence of a relative with renal failure, and low socioeconomic levels could be suggested as risk factors for phobia of renal failure.
Mutation spectrum and biochemical features in infants with neonatal Dubin-Johnson syndrome
Authors: Kim Kwang Yeon , Kim Tae Hyeong , Seong Moon-Woo , Park Sung Sup , Moon Jin Soo , Ko Jae Sung
Published: August 2020

Background

Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder presenting as isolated direct hyperbilirubinemia.DJS is rarely diagnosed in the neonatal period. The purpose of this study was to clarify the clinical features of neonatal DJS and to analyze the genetic mutation of adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2).

Methods

From 2013 to 2018, 135 infants with neonatal cholestasis at Seoul National University Hospital were enrolled. Genetic analysis was performed by neonatal cholestasis gene panel. To clarify the characteristics of neonatal DJS, the clinical and laboratory results of 6 DJS infants and 129 infants with neonatal cholestasis from other causes were compared.

Results

A total of 8 different ABCC2 variants were identified among the 12 alleles of DJS. The most common variant was p.Arg768Trp (33.4%), followed by p.Arg100Ter (16.8%). Three novel variants were identified (p.Gly693Glu, p.Thr394Arg, and p.Asn718Ser). Aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in infants with DJS than in infants with neonatal cholestasis from other causes. Direct bilirubin and total bilirubin were significantly higher in the infants with DJS.

Conclusions

We found three novel variants in 6 Korean infants with DJS. When AST and ALT levels are normal in infants with neonatal cholestasis, genetic analysis of ABCC2 permits an accurate diagnosis.
Analysis of serum polyunsaturated fatty acid metabolites in allergic bronchopulmonary aspergillosis
Authors: Li Lu , Wu Jianlin , Bian Xiqing , Wu Ge , Zheng Peiyan , Xue Mingshan , Sun Baoqing
Published: August 2020

Background

The importance of lipid mediators in allergic diseases has been long recognized, whereas little is known about their role in allergic bronchopulmonary aspergillosis (ABPA). We investigated whether lipid mediators are associated with ABPA.

Methods

We recruited 12 ABPA patients, 23 asthma patients and 12 healthy control in our study. Serum of 11 ABPA patients were collected before and following treatment. 36 polyunsaturated fatty acid metabolites were measured in serum samples by using liquid chromatography–mass spectrometry. This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University, with ethics number GYFYY-2016-73.

Results

Levels of arachidonic acid (AA), 15(S)-hydroxyeicosatetraenoic acid (HETE), 12(S)-HETE, 8(S)-HETE, 5(S)-HETE, LTB4, PGB2, 12(S)-hydroxyeicosapentaenoic acid (HEPE), 12-hydro-xyheptadecatrienoic acid (HHTrE) were significantly higher in ABPA patients than that in HC groups. Compared with asthma group, ABPA group expressed lower levels of 15(S)-hy-droperoxyeicosatetraenoic acid (HPETE), 5(S)-HPETE, 13(S)-hydroperoxyoctadecadienoic acid (HPODE) and 9(S)-HPODE. In APBA patients, AA level was positively correlated with serumtotal IgE (tIgE). The levels of 12(S)-HPETE, 15(S)-HEPE and 12(S)-HEPE correlated with Asp-ergillus fumigatus specific IgE(A. fumigatus sIgE) positively. Peripheral blood eosinophilia correlated with high levels of 12(S)-HETE and 15(S)-HETE. In addition, the serum levels of15(S)-HETE and 12(S)-HETE in ABPA subjects both declined with the decrease of tIgE, A. fumigatus sIgE and sIgG concentrations after treatment.

Conclusions

We present data regarding the role of polyunsaturated fatty acid metabolites in APBA for the first time. Most of the tested metabolites increased in ABPA when co-mpared with healthy controls and 15(S)-HETE and 12(S)-HETE may play a role in the pat-hogenesis of ABPA. These findings can provide new ideas for diagnosis, therapy and mon-itor of ABPA.
A comprehensive framework for considering additional unintended consequences in economic evaluation
Authors: Nymark Liv , Vassall Anna
Published: August 2020

Background

In recent years there has been a growth in economic evaluations that consider indirect health benefits to populations due to advances in mathematical modeling. In addition, economic evaluations guidelines have suggested the inclusion of impact inventories to include non-health direct and indirect consequences. We aim to bring together this literature, together with the broader literature on internalities and externalities to propose a comprehensive approach for analysts to identify and characterize all unintended consequences in economic evaluations.

Methods

We present a framework to assist analysts identify and characterize additional costs and effects beyond that of direct health impact primarily intended to be influenced by the intervention/technology. We build on previous checklists to provide analysts with a comprehensive framework to justify the inclusion or exclusion of effects, supporting the use of current guidelines, to ensure any unintended effects are considered. We illustrate this framework with examples from immunization. These were identified from a previous systematic review, PhD thesis work, and general search scoping in PubMed databases.

Results

We present a comprehensive framework to consider additional consequences, exemplified by types and categories. We bring this and other guidance together to assist analysts identify possible unintended consequences whether taking a provider or societal perspective.

Conclusions

Although there are many challenges ahead to standardize the inclusion of additional consequences in economic evaluation, we hope by moving beyond generic statements to reporting against a comprehensive framework of additional effects we can support further consistency in this aspect of cost-effectiveness analysis going forward.
Assisted hatching of vitrified-warmed blastocysts prior to embryo transfer does not improve pregnancy outcomes
Authors: Ng Charis , Wais Marta , Nichols Taryn , Garrow Sarah , Hreinsson Julius , Luo Zhong-Cheng , Chan Crystal
Published: August 2020

Objective

This study aims to determine the impact of assisted hatching (AH) on pregnancy outcomes in vitrified-warmed blastocyst transfers, and evaluate if embryo expansion or morphology influences outcomes.

Methods

A retrospective cohort study was performed including vitrified-warmed blastocyst transfers at our clinic between 2013 and 2017. Of the 2165 embryo transfers, 1986 underwent laser AH and 179 were non-assisted hatched (NAH). The primary outcome was live birth. Secondary outcomes included conception, implantation, clinical pregnancy, clinical pregnancy loss, and monozygotic twinning (MZT).

Results

AH and NAH groups had similar rates of conception (38.7% vs 42.1%), implantation (26.2% vs 27.3%), clinical pregnancy (29.1% vs 30.3%), clinical pregnancy loss (24.0% vs 17.8%), live birth (19.9% vs 20.5%), and MZT (2.08% vs 2.86%). Five pairs of dichorionic/diamniotic twins resulted from single embryo transfers. AH of embryos with expansion grades ≤3 was associated with lower rates of conception (32.5% vs 44.3%%, p < 0.05) and clinical pregnancy (24.0% vs 32.8%, p < 0.05).

Conclusion

AH prior to transfer of vitrified-warmed blastocysts was not associated with improved pregnancy outcomes. The identification of dichorionic/diamniotic twins from single blastocyst transfers challenges the previously held notion that dichorionic/diamniotic MZTs can only occur from division prior to the blastocyst stage. Prospective studies are needed to validate the novel finding of lower rates of conception and clinical pregnancy after AH in embryos with lower expansion grade.
Correction to: Urine cell cycle arrest biomarkers distinguish poorly between transient and persistent AKI in early septic shock: a prospective, multicenter study
Authors: Titeca-Beauport Dimitri , Daubin Delphine , Van Vong Ly , Belliard Guillaume , Bruel Cédric , Alaya Sami , Chaoui Karim , Andrieu Maud , Rouquette-Vincenti Isabelle , Godde Frederic , Pascal Michel , Diouf Momar , Vinsonneau Christophe , Klouche Kada , Maizel Julien
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Microencapsulation of cellular aggregates composed of differentiated insulin and glucagon-producing cells from human mesenchymal stem cells derived from adipose tissue
Authors: Jara Claudia , Oyarzun-Ampuero Felipe , Carrión Flavio , González-Echeverría Esteban , Cappelli Claudio , Caviedes Pablo
Published: August 2020

Background

In type I diabetes mellitus (T1DM) pancreatic β cells are destroyed. Treatment entails exogenous insulin administration and strict diet control, yet optimal glycemic control is hardly attainable. Islet transplant could be an alternative in patients with poor glycemic control, but inefficient islet purification and autoimmune response of patients is still a challenge. For these reasons, it is necessary to explore new cellular sources and immunological isolation methods oriented to develop T1DM cell-based therapies.

Aims

We postulate human adipose-derived stem cell (hASC) as an adequate source to generate pancreatic islet cells in vitro, and to produce islet-like structures. Furthermore, we propose microencapsulation of these aggregates as an immunological isolation strategy.

Methods

hASC obtained from lipoaspirated fat tissue from human donors were differentiated in vitro to insulin (Ins) and glucagon (Gcg) producing cells. Then, insulin producing cells (IPC) and glucagon producing cells (GPC) were cocultured in low adhesion conditions to form cellular aggregates, and later encapsulated in a sodium alginate polymer. Expression of pancreatic lineage markers and secretion of insulin or glucagon in vitro were analyzed.

Results

The results show that multipotent hASC efficiently differentiate to IPC and GPC, and express pancreatic markers, including insulin or glucagon hormones which they secrete upon stimulation (fivefold for insulin in IPC, and fourfold for glucagon, compared to undifferentiated cells). In turn, calculation of the Feret diameter and area of cellular aggregates revealed mean diameters of ~ 80 µm, and 65% of the aggregates reached 4000 µm2 at 72 h of formation. IPC/GPC aggregates were then microencapsulated in sodium-alginate polymer microgels, which were found to be more stable when stabilized with Ba2+, yielding average diameters of ~ 300 µm. Interestingly, Ba2+-microencapsulated aggregates respond to high external glucose with insulin secretion.

Conclusions

The IPC/GPC differentiation process from hASC, followed by the generation of cellular aggregates that are later microencapsulated, could represent a possible treatment for T1DM.
Management of epigenomic networks entailed in coronavirus infections and COVID-19
Authors: El Baba Ranim , Herbein Georges
Published: August 2020

Coronaviruses (CoVs) are highly diverse single-stranded RNA viruses owing to their susceptibility to numerous genomic mutations and recombination. Such viruses involve human and animal pathogens including the etiologic agents of acute respiratory tract illnesses: severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the highly morbific SARS-CoV-2. Coronavirus disease 2019 (COVID-19), an emerging disease with a quick rise in infected cases and deaths, was recently identified causing a worldwide pandemic. COVID-19 disease outcomes were found to increase in elderly and patients with a compromised immune system. Evidences indicated that the main culprit behind COVID-19 deaths is the cytokine storm, which is illustrated by an uncontrolled over-production of soluble markers of inflammation. The regulation process of coronavirus pathogenesis through molecular mechanism comprise virus-host interactions linked to viral entry, replication and transcription, escape, and immune system control. Recognizing coronavirus infections and COVID-19 through epigenetics lens will lead to potential alteration in gene expression thus limiting coronavirus infections. Focusing on epigenetic therapies reaching clinical trials, clinically approved epigenetic-targeted agents, and combination therapy of antivirals and epigenetic drugs is currently considered an effective and valuable approach for viral replication and inflammatory overdrive control.
Neurodegenerative changes in early- and late-onset cognitive impairment with and without brain amyloidosis
Authors: Stage Eddie C. , Svaldi Diana , Phillips Meredith , Canela Victor Hugo , Duran Tugce , Goukasian Naira , Risacher Shannon L. , Saykin Andrew J. , Apostolova Liana G. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2020

Background

A substantial number of patients clinically diagnosed with Alzheimer’s disease do not harbor amyloid pathology. We analyzed the presence and extent of tau deposition and neurodegeneration in amyloid-positive (AD) and amyloid-negative (nonAD) ADNI subjects while also taking into account age of onset (< or > 65 years) as we expected that the emerging patterns could vary by age and presence or absence of brain amyloidosis.

Methods

One hundred and ten early-onset AD (EOAD), 121 EOnonAD, 364 late-onset AD (LOAD), and 175 LOnonAD mild cognitive impairment (MCI) and dementia (DEM) subjects were compared to 291 ADNI amyloid-negative control subjects using voxel-wise regression in SPM12 with cluster-level family-wise error correction at pFWE < 0.05). A subset of these subjects also received 18F-flortaucipir scans and allowed for analysis of global tau burden.

Results

As expected, relative to LOAD, EOAD subjects showed more extensive neurodegeneration and tau deposition in AD-relevant regions. EOnonADMCI showed no significant neurodegeneration, while EOnonADDEM showed bilateral medial and lateral temporal, and temporoparietal hypometabolism. LOnonADMCI and LOnonADDEM showed diffuse brain atrophy and a fronto-temporo-parietal hypometabolic pattern. LOnonAD and EOnonAD subjects failed to show significant tau binding.

Conclusions

LOnonAD subjects show a fronto-temporal neurodegenerative pattern in the absence of tau binding, which may represent underlying hippocampal sclerosis with TDP-43, also known as limbic-predominant age-related TDP-43 encephalopathy (LATE). The hypometabolic pattern observed in EOnonADDEM seems similar to the one observed in EOADMCI. Further investigation into the underlying etiology of EOnonAD is warranted.
Alexithymia may explain the relationship between autistic traits and eating disorder psychopathology
Authors: Vuillier L. , Carter Z. , Teixeira A. R. , Moseley R. L.
Published: August 2020

Background

Autistic people are disproportionately vulnerable to anorexia nervosa and other eating disorders (ED), and within the general population, autistic traits correlate with ED psychopathology. A putative mechanism which may underpin this heightened risk is alexithymia, a difficulty identifying and describing emotional states which is observed in both autism and ED. In two experiments with independent non-clinical samples, we explored whether alexithymia might mediate the heightened risk of eating psychopathology in individuals high in autistic traits.

Methods

Our first experiment used the PROCESS macro for SPSS to examine relationships between alexithymia (measured by the Toronto Alexithymia Scale (TAS-20)), autistic traits (autism quotient (AQ)), and eating psychopathology (Eating Attitudes Test (EAT-26)) in 121 participants. Our second experiment (n= 300) replicated and furthered this analysis by examining moderating effects of sex and controlling for anxiety and depression as covariates. We also included an additional performance-based measure of alexithymia, the Levels of Emotional Awareness Scale (LEAS).

Results

Study 1 suggested that TAS-20 scores mediated the relationship between heightened autistic traits and eating psychopathology. Replication and further scrutiny of this finding, in study 2, revealed that this mediation effect was partial and specific to the female participants in this sample. The mediation effect appeared to be carried by the difficulty identifying feelings subscale of the TAS-20, even when depression and anxiety were controlled for. LEAS scores, however, were not significantly related to autistic traits or eating psychopathology.

Limitations

Cross-sectional data prevents any conclusions around the direction and causality of relationships between alexithymia, autistic traits, and eating psychopathology (alongside depression and anxiety), necessitating longitudinal research. Our non-clinical sample was predominantly Caucasian undergraduate students, so it remains to be seen if these results would extrapolate to clinical and/or autistic samples. Divergence between the TAS-20 and LEAS raises crucial questions regarding the construct validity of these measures.

Conclusions

Our findings with respect to autistic traits suggest that alexithymia could partially explain the prevalence of ED in autistic people and may as such be an important consideration in the pathogenesis and treatment of ED in autistic and non-autistic people alike. Further research with clinical samples is critical to explore these ideas. Differences between men and women, furthermore, emphasize the importance of looking for sex-specific as well as generic risk factors in autistic and non-autistic men and women.
Bilateral torsion of fallopian tubes with bilateral hydrosalpinx: a case report
Authors: Kartal Taner , Birge Ozer
Published: August 2020

Background

Isolated fallopian tube torsion is a very rare cause of acute abdominal pain in women and, as can be expected, its being bilateral is an extremely rare condition. It is more common in women in reproductive age compared to other age groups. Symptoms, physical examination, imaging and laboratory findings being nonspecific makes it difficult to establish the correct diagnosis and often the diagnosis can be made during surgery. Despite being a very rare condition in general, it is important in terms of preservation of tube and thus the fertility especially in women of reproductive age with early diagnosis and treatment. Therefore, keeping in mind the fallopian tube torsion among the differential diagnoses in women presenting with acute abdominal pain will contribute to early diagnosis and treatment.

Case presentation

A 38-year-old white Arabian woman, gravida 1, parity 0, abort 1, sought medical advice in our outpatient clinic with a complaint of lower abdominal pain that had started 2 days earlier. The pain had first started as mild cramps, which then suddenly intensified nearly 2 hours before her presentation to our clinic, spread to the groin and femur, more prominent on the right side, and became an ongoing pain. As preoperative diagnoses of the patient, ovarian cyst rupture and ectopic pregnancy were suspected, and fallopian tube torsion was also suspected due to the normal appearance of the ovaries and the appearance of the hydrosalpinx on ultrasonography. The patient underwent laparotomy with a Pfannenstiel incision. Both tubes had hydrosalpinx, and the fimbrial ends were blunt and obliterated. Bilateral salpingectomy was performed because the right tube had a prominent necrotic appearance, and there was a significant hydrosalpinx in both tubes.

Conclusion

Bilateral fallopian tube torsion should be considered among the differential diagnoses in women presenting with acute pelvic pain.
Comment on “Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study”
Authors: Stessuk Talita , Ribeiro-Paes João Tadeu
Published: August 2020

In the clinical study by Le Thi Bich et al., allogeneic expanded umbilical cord-derived mesenchymal stem cells (UC-MSCs) were intravenously infused to treat patients with chronic obstructive pulmonary disease (COPD). No severe or significant adverse effects were observed, while a significant improvement in COPD patients’ quality of life was reported up to 6 months. In addition, the authors argue that bone marrow-derived cells are not suitable to treat COPD based on the “failure” of 3 clinical trials (NCT01110252, NCT01306513, and NCT00683722). In fact, Le Thi Bich et al. and the three above-mentioned studies reported similar clinical outcomes, id est., no significant improvement in the pulmonary function of COPD patients. Therefore, since no COPD treatment involving cells either from bone marrow or umbilical cord was detrimental or provided lung regeneration in human patients, in our view, it is too early to point failures of cellular sources. Instead, it is a valuable opportunity to reflect on the poorly understood therapeutic mechanism of MSCs and the pathophysiology of COPD. In respect of cellular sources, only controlled trials with a strict comparison between different tissues might determine the suitability and efficacy of specific cell types to treat COPD. Finally, further studies are still required to determine whether and via which mechanism MSCs are able to provide structural and functional restoration of gas exchange in COPD patients.
A new 68Ga-labeled somatostatin analog containing two iodo-amino acids for dual somatostatin receptor subtype 2 and 5 targeting
Authors: Mansi Rosalba , Abid Karim , Nicolas Guillaume P. , Del Pozzo Luigi , Grouzmann Eric , Fani Melpomeni
Published: August 2020

Background

Somatostatin receptor (SST) targeting, specifically of the subtype 2 (SST2), with radiolabeled somatostatin analogs, is established for imaging and treatment of neuroendocrine tumors. Owing to the concomitant and heterogeneous expression of several subtypes on the same tumor, analogs targeting more subtypes than SST2 potentially target a broader spectrum of tumors and/or increase the uptake of a given tumor. The analog ST8950 ((4-amino-3-iodo)-d-Phe-c[Cys-(3-iodo)-Tyr-d-Trp-Lys-Val-Cys]-Thr-NH2), bearing 2 iodo-amino acids, exhibits sub-nanomolar affinity to SST2 and SST5. We report herein the development and preclinical evaluation of DOTA-ST8950 labeled with68Ga, for imaging SST2- and SST5-expressing tumors. Comparative in vitro and in vivo studies were performed with the de-iodinated DOTA-ST8951 ((4-amino)-d-Phe-c[Cys-Tyr-d-Trp-Lys-Val-Cys]-Thr-NH2) and with the reference compounds DOTA-TATE (SST2 selective) and DOTA-NOC (for SST2 and SST5).

Results

Compared withnatGa-DOTA-NOC,natGa-DOTA-ST8950 exhibited higher affinity to SST2 and SST5 (IC50(95%CI), nM = 0.32 (0.20–0.50) and 1.9 (1.1–3.1) vs 0.70 (0.50-0.96) and 3.4 (1.8-6.2), respectively), whilenatGa-DOTA-ST8951 lost affinity for both subtypes.natGa-DOTA-ST8950 had the same potency for inducing SST2-mediated cAMP accumulation asnatGa-DOTA-TATE and slightly better thannatGa-DOTA-NOC (EC50, nM = 0.46 (0.23–0.92) vs 0.47 (0.15–1.5) vs 0.59 (0.18–1.9), respectively). [67Ga]Ga-DOTA-ST8950 had a similar internalization rate as [67Ga]Ga-DOTA-NOC in SST2-expressing cells (12.4 ± 1.6% vs 16.6 ± 2.2%, at 4 h,p= 0.0586). In vivo, [68Ga]Ga-DOTA-ST8950 showed high and specific accumulation in SST2- and SST5-expressing tumors, comparable with [68Ga]Ga-DOTA-NOC (26 ± 8 vs 30 ± 8 %IA/g,p= 0.4630 for SST2 and 15 ± 6 vs 12 ± 5 %IA/g,p= 0.3282, for SST5, 1 h p.i.) and accumulation in the SST-positive tissues, the kidneys and the liver. PET/CT images of [68Ga]Ga-DOTA-ST8950, performed in a dual HEK-SST2 and HEK-SST5 tumor xenografted model, clearly visualized both tumors and illustrated high tumor-to-background contrast.

Conclusions

[68Ga]Ga-DOTA-ST8950 reveals its potential for PET imaging SST2- and SST5-expressing tumors. It compares favorably with the clinically used [68Ga]Ga-DOTA-NOC in terms of tumor uptake; however, its uptake in the liver remains a challenge for clinical translation. In addition, this study reveals the essential role of the iodo-substitutions in positions 1 and 3 of [68Ga]Ga-DOTA-ST8950 for maintaining affinity to SST2 and SST5, as the de-iodinated [68Ga]Ga-DOTA-ST8951 lost affinity for both receptor subtypes.
Preliminary evidence of imaging of chemokine receptor-4-targeted PET/CT with [68Ga]pentixafor in non-Hodgkin lymphoma: comparison to [18F]FDG
Authors: Pan Qingqing , Luo Yaping , Zhang Yan , Chang Long , Li Ji , Cao Xinxin , Li Jian , Li Fang
Published: August 2020

Background

In order to study the CXCR4 expression with [68Ga]pentixafor PET in different types of non-Hodgkin lymphoma, we performed a retrospective study to describe the [68Ga]pentixafor PET/CT imaging in a spectrum of lymphomas and to compare it with [18F]FDG PET/CT.

Results

Twenty-seven patients with newly diagnosed non-Hodgkin lymphoma were recruited retrospectively. [68Ga]pentixafor PET showed increased radioactivity in lymphoplasmacytic lymphoma (n = 8), marginal zone lymphoma (n = 4), diffuse large B cell lymphoma (n = 3), follicular lymphoma (n = 2), mantle cell lymphoma (n = 1), unclassified indolent B cell lymphoma (n = 3), and enteropathy associated T cell lymphoma (n = 3). However, peripheral T cell lymphoma, not otherwise specified (n = 1), and NK/T cell lymphoma (n = 2) were not avid for [68Ga]pentixafor. In comparison to [18F]FDG PET, [68Ga]pentixafor PET demonstrated more extensive disease and higher radioactivity in lymphoplasmacytic lymphoma and marginal zone lymphoma.

Conclusion

CXCR4 expression varies in different types of non-Hodgkin lymphoma. Overexpression of CXCR4 was detected with [68Ga]pentixafor PET/CT in lymphoplasmacytic lymphoma, marginal zone lymphoma, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, unclassified indolent B cell lymphoma, and enteropathy associated T cell lymphoma. The uptake of [68Ga]pentixafor was higher than [18F]FDG in lymphoplasmacytic lymphoma and marginal zone lymphoma.
Improving the production of AHL lactonase AiiO-AIO6 from Ochrobactrum sp. M231 in intracellular protease-deficient Bacillus subtilis
Authors: Xia Rui , Yang Yalin , Pan Xingliang , Gao Chenchen , Yao Yuanyuan , Liu Xuewei , Teame Tsegay , Zhang Fengli , Hu Juan , Ran Chao , Zhang Zhen , Liu-Clarke Jihong , Zhou Zhigang
Published: August 2020

Quorum quenching (QQ) blocks bacterial cell-to-cell communication (i.e., quorum sensing), and is a promising antipathogenic strategy to control bacterial infection via inhibition of virulence factor expression and biofilm formation. QQ enzyme AiiO-AIO6 fromOchrobactrumsp. M231 has several excellent properties and shows biotherapeutic potential against important bacterial pathogens of aquatic species. AiiO-AIO6 can be secretory expressed inBacillus subtilisvia a non-classical secretion pathway. To improve AiiO-AIO6 production, four intracellular protease-deletion mutants ofB. subtilis1A751 were constructed by individually knocking out the intracellular protease-encoding genes (tepA, ymfH, yrrN and ywpE). The AiiO-AIO6 expression plasmid pWB-AIO6BS was transformed into theB. subtilis1A751 and its four intracellular protease-deletion derivatives. Results showed that all recombinant intracellular protease-deletion derivatives (BSΔtepA, BSΔymfH, BSΔyrrNand BSΔywpE) had a positive impact on AiiO-AIO6 production. The highest amount of AiiO-AIO6 extracellular production of BSΔywpEin shake flask reached 1416.47 U/mL/OD600, which was about 121% higher than that of the wild-type strain. Furthermore, LC–MS/MS analysis of the degrading products of 3-oxo-C8-HSL by purification of AiiO-AIO6 indicated that AiiO-AIO6 was an AHL-lactonase which hydrolyzes the lactone ring of AHLs. Phylogenetic analysis showed that AiiO-AIO6 was classified as a member of the α/β hydrolase family with a conserved “nucleophile-acid-histidine” catalytic triad. In summary, this study showed that intracellular proteases were responsible for the reduced yields of heterologous proteins and provided an efficient strategy to enhance the extracellular production of AHL lactonase AiiO-AIO6.
Parallel acceleration of CPU and GPU range queries over large data sets
Authors: Nelson Mitchell , Sorenson Zachary , Myre Joseph M. , Sawin Jason , Chiu David
Published: August 2020

Data management systems commonly use bitmap indices to increase the efficiency of querying scientific data. Bitmaps are usually highly compressible and can be queried directly using fast hardware-supported bitwise logical operations. The processing of bitmap queries is inherently parallel in structure, which suggests they could benefit from concurrent computer systems. In particular, bitmap-range queries offer a highly parallel computational problem, and the hardware features of graphics processing units (GPUs) offer an alluring platform for accelerating their execution.In this paper, we present four GPU algorithms and two CPU-based algorithms for the parallel execution of bitmap-range queries. We show that in 98.8% of our tests, using real and synthetic data, the GPU algorithms greatly outperform the parallel CPU algorithms. For these tests, the GPU algorithms provide up to 54.1 × speedup and an average speedup of 11.5× over the parallel CPU algorithms. In addition to enhancing performance, augmenting traditional bitmap query systems with GPUs to offload bitmap query processing allows the CPU to process other requests.