bluuebunny/crossref_metadata_2025 huggingface dataset:
Boxed In: Beliefs about the Compatibility and Likability of Mother-Occupation and Father-Occupation Role Combinations
Authors: Noonan Mary C. , Lynn Freda B. , Walker Mark H.
Published: July 2020

Researchers have long noted that role expectations of a “good” mother conflict with those of a “good” worker, described as the “cultural contradiction” of motherhood. But given that work roles vary tremendously in terms of the cultural meanings the public assigns them, the authors examine variability in the perceived compatibility of mother-occupation and father-occupation combinations. Building on previous research, the authors hypothesize that (1) some parent-occupation pairings will be viewed as significantly less compatible because of incongruent expectations and meanings, and (2) incumbents of supposedly compatible parent-occupation pairings will be evaluated more favorably than incumbents of incompatible pairings. Both hypotheses are tested using original survey data on perceptions of mothers and fathers in 28 occupations merged with occupational characteristics from secondary data sources. The results strongly suggest that even though there are well-known prescriptive norms for both mothers and fathers, mothers’ occupational choices are more actively policed compared with fathers’.
Ventral midline thalamus is not necessary for systemic consolidation of a social memory in the rat
Authors: Quet Etienne , Cassel Jean-Christophe , Cosquer Brigitte , Galloux Marine , Pereira De Vasconcelos Anne , Stéphan Aline
Published: July 2020

According to the standard theory of memory consolidation, recent memories are stored in the hippocampus before their transfer to cortical modules, a process called systemic consolidation. The ventral midline thalamus (reuniens and rhomboid nuclei, ReRh) takes part in this transfer as its lesion disrupts systemic consolidation of spatial and contextual fear memories. Here, we wondered whether ReRh lesions would also affect the systemic consolidation of another type of memory, namely an olfaction-based social memory. To address this question we focused on social transmission of food preference. Adult Long-Evans rats were subjected to N-methyl-d-aspartate-induced, fibre-sparing lesions of the ReRh nuclei or to a sham-operation, and subsequently trained in a social transmission of food preference paradigm. Retrieval was tested on the next day (recent memory, nSham = 10, nReRh = 12) or after a 25-day delay (remote memory, nSham = 10, nReRh = 10). All rats, whether sham-operated or subjected to ReRh lesions, learned and remembered the task normally, whatever the delay. Compared to our former results on spatial and contextual fear memories (Ali et al., 2017; Klein et al., 2019; Loureiro et al., 2012; Quet et al., 2020), the present findings indicate that the ReRh nuclei might not be part of a generic, systemic consolidation mechanism processing all kinds of memories in order to make them persistent. The difference between social transmission of food preference and spatial or contextual fear memories could be explained by the fact that social transmission of food preference is not hippocampus-dependent and that the persistence of social transmission of food preference memory relies on different circuits.
Biopolitics of migration: An assemblage approach
Authors: Wiertz Thilo
Published: July 2020

Critical research on migration, borders and camps has used the notion of biopolitics to interrogate how sovereign power or the state differentiate and govern the life of mobile populations. Yet despite its popularity, biopolitical theory is not without limitations, particularly when used as an analytic lens for empirical research. Many theorists of biopolitics are concerned with grand historical shifts and binary oppositions between life and death, inclusion and exclusion, bare life and political rights. Such binaries have been challenged by recent research that points to complex and nuanced differentiations of belonging and citizenship, to the ambiguity of power relations, and that prioritizes the agency and experience of individuals over structuralist conceptions of oppression. Against this background, I suggest that assemblage thinking and the works of Deleuze and Guattari offer terms and concepts that can be made useful to reconsider biopolitics as an analytic approach. Assemblage thinking challenges traditional oppositions between the individual and the collective, structure and agency, oppression and resistance and may thus be more sensitive to the complexity of power relations that integrate the life of migrants. In particular, I examine how revised conceptions of power, life, difference and population challenge the assumption of a central origin of power and an understanding of biopolitics as spatially or historically confined. By considering biopolitics as multiple and becoming, analysis can become more sensitive to the biopolitical experience of migrants, and to the formation of alternative collectives and subjectivities that challenge the violent biopolitics of contemporary migration regimes.
Interweaving Between Genetic and Epigenetic Studies on Childhood Asthma
Authors: Rathod Aniruddha , Duan Jiasong , Zhang Hongmei , Holloway John W , Ewart Susan , Arshad S Hasan , Karmaus Wilfried
Published: July 2020

The cause and underlying mechanisms that contribute to asthma pathogenesis are not well known. Both genome- and epigenome-wide association studies have identified genes associated with asthma risk. It is unknown to what extent genes identified in these two types of studies overlap. Based on existing literature and the DisGeNET database, we extracted overlapping genes identified in genetic and epigenetic studies of childhood asthma. Through analyses of variance, we assessed whether DNA methylation (DNAm) at 5′-C-phosphate-G-3′ (CpGs) on the overlapping genes was associated with neighboring single-nucleotide polymorphisms (SNPs) within 1M base pairs (bps) and with low linkage disequilibrium ( r2  < 0.2) in the childhood asthma-related genes. In total, 285 genes from genetic studies and 226 genes from epigenetic studies were shown to be associated with asthma risk, of which six overlap. Of the six genes, 79 CpGs and 8229 unique neighboring SNPs (1M bps) were included in methylation quantitative loci (methQTL) assessment analyses. We tested the association of DNAm at each of the 79 CpG sites with its neighboring SNPs. After adjusting for multiple testing by controlling the false discovery rate to 0.05 when testing methQTL for each CpG site, we found statistically significant associations in three genes with their neighboring SNPs and identified 34 unique methQTLs. The rather limited overlap in genes between genetic and epigenetic studies on asthma and the absence of methQTL in some of the overlapping genes highlight a need to jointly, rather than independently, examine genetic and epigenetic effects on asthma risk to improve our understanding of the underlying mechanisms of asthma.
Indo-Pacific Order and Japan–India Relations in the Midst of COVID-19
Authors: Horimoto Takenori
Published: July 2020

Because of the USA’s relative decline of national power and the rapid emergence of China, the Indo-Pacific lacks a regional order as existed during the latter half of the twentieth century. The USA and China have had strained relations since the 2010s as economic and hegemonic rivals. Furthermore, at the cusp of the 2020s, a blame game is unfolding over COVID-19. Neither nation can be expected to serve a role as an order manager of peace and stability in the Indo-Pacific. Under such international situations, Japan and India should cooperate to initiate consideration of the regional order now. To establish such an order for the future, ends and means carry an importance. The ends should be the creation of a free, open, inclusive and democratic Indo-Pacific. The means should be some mechanisms based on principles of multilateralism, for example, Quad-Plus, not only involving the four countries: like-minded countries should also be included. In this way, we can find a silver lining beyond COVID-19.

JEL Codes: F5, I19
Thought Experiments and Philosophy in Organizational Research
Authors: Kornberger Martin , Mantere Saku
Published: July 2020

Organization theory seems to be caught between a rock and a hard place: on the one hand, there are arguments that the field is too preoccupied with theory, leaving its work abstract and practically irrelevant. On the other hand, there are arguments that the field is overly empirical and too methods-driven, which hampers the creation of ideas that resonate with constituencies beyond the organization studies community. How to resolve this apparent conundrum? In this essay we argue that neither more theorizing nor more forensic data-driven work might address the problem; rather, and perhaps surprisingly, we propose that a philosophical stance might offer a remedy. The aim of this essay is (1) to explore thought experiments as a genuine philosophical method that is designed to develop promising ideas and concepts and (2) to reflect on how such conceptual work can help shape organization theory to be conceptually more stimulating and practically more relevant. We argue that this particular kind of conceptual work has been and should continue to be one of the hallmarks of organization theory. Thus thought experiments represent a valuable methodological extension of our toolkit as they provide crucial devices triggering transformations in thought and practice.
DNA Methylation Clocks and Their Predictive Capacity for Aging Phenotypes and Healthspan
Authors: Bergsma Tessa , Rogaeva Ekaterina
Published: July 2020

The number of age predictors based on DNA methylation (DNAm) profile is rising due to their potential in predicting healthspan and application in age-related illnesses, such as neurodegenerative diseases. The cumulative assessment of DNAm levels at age-related CpGs (DNAm clock) may reflect biological aging. Such DNAm clocks have been developed using various training models and could mirror different aspects of disease/aging mechanisms. Hence, evaluating several DNAm clocks together may be the most effective strategy in capturing the complexity of the aging process. However, various confounders may influence the outcome of these age predictors, including genetic and environmental factors, as well as technical differences in the selected DNAm arrays. These factors should be taken into consideration when interpreting DNAm clock predictions. In the current review, we discuss 15 reported DNAm clocks with consideration for their utility in investigating neurodegenerative diseases and suggest research directions towards developing a more optimal measure for biological aging.
Pulmonary function testing in children's interstitial lung disease
Authors: Ring Astrid Madsen , Carlens Julia , Bush Andy , Castillo-Corullón Silvia , Fasola Salvatore , Gaboli Mirella Piera , Griese Matthias , Koucky Vaclav , La Grutta Stefania , Lombardi Enrico , Proesmans Marijke , Schwerk Nicolaus , Snijders Deborah , Nielsen Kim Gjerum , Buchvald Frederik
Published: July 2020

The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease.

A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome.

PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials.
Respiratory viral sepsis: epidemiology, pathophysiology, diagnosis and treatment
Authors: Gu Xiaoying , Zhou Fei , Wang Yeming , Fan Guohui , Cao Bin
Published: July 2020

According to the Third International Consensus Definition for Sepsis and Septic Shock, sepsis is a life-threatening organ dysfunction resulting from dysregulated host responses to infection. Epidemiological data about sepsis from the 2017 Global Burden of Diseases, Injuries and Risk Factor Study showed that the global burden of sepsis was greater than previously estimated. Bacteria have been shown to be the predominant pathogen of sepsis among patients with pathogens detected, while sepsis caused by viruses is underdiagnosed worldwide. The coronavirus disease that emerged in 2019 in China and now in many other countries has brought viral sepsis back into the vision of physicians and researchers worldwide. Although the current understanding of the pathophysiology of sepsis has improved, the differences between viral and bacterial sepsis at the level of pathophysiology are not well understood. Diagnosis methods that can broadly differentiate between bacterial and viral sepsis at the initial stage after the development of sepsis are limited. New treatments that can be applied at clinics for sepsis are scarce and this situation is not consistent with the growing understanding of pathophysiology. This review aims to give a brief summary of current knowledge of the epidemiology, pathophysiology, diagnosis and treatment of viral sepsis.
Developments in lung transplantation over the past decade
Authors: van der Mark Sophie C. , Hoek Rogier A.S. , Hellemons Merel E.
Published: July 2020

With an improved median survival of 6.2 years, lung transplantation has become an increasingly acceptable treatment option for end-stage lung disease. Besides survival benefit, improvement of quality of life is achieved in the vast majority of patients. Many developments have taken place in the field of lung transplantation over the past decade. Broadened indication criteria and bridging techniques for patients awaiting lung transplantation have led to increased waiting lists and changes in allocation schemes worldwide. Moreover, the use of previously unacceptable donor lungs for lung transplantation has increased, with donations from donors after cardiac death, donors with increasing age and donors with positive smoking status extending the donor pool substantially. Use ofex vivolung perfusion further increased the number of lungs suitable for lung transplantation. Nonetheless, the use of these previously unacceptable lungs did not have detrimental effects on survival and long-term graft outcomes, and has decreased waiting list mortality. To further improve long-term outcomes, strategies have been proposed to modify chronic lung allograft dysfunction progression and minimise toxic immunosuppressive effects. This review summarises the developments in clinical lung transplantation over the past decade.
Wild mice with different social network sizes vary in brain gene expression
Authors: Lopes Patricia C. , König Barbara
Published: July 2020

Background

Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution of egocentric network sizes (characterized by number of different partners encountered per day). We then used RNA-seq to perform an unbiased assessment of neural differences in gene expression in the prefrontal cortex, the hippocampus and the hypothalamus between these mice with naturally occurring extreme differences in social network size.

Results

We found that the neurogenomic pathways associated with having extreme social network sizes differed between the sexes. In females, hundreds of genes were differentially expressed between animals with small and large social network sizes, whereas in males very few were. In males, X-chromosome inactivation pathways in the prefrontal cortex were the ones that better differentiated animals with small from those with large social network sizes animals. In females, animals with small network size showed up-regulation of dopaminergic production and transport pathways in the hypothalamus. Additionally, in females, extracellular matrix deposition on hippocampal neurons was higher in individuals with small relative to large social network size.

Conclusions

Studying neural substrates of natural variation in social behavior in traditional model organisms in their habitat can open new targets of research for understanding variation in social behavior in other taxa.
Opposing effects of antibiotics and germ-free status on neuropeptide systems involved in social behaviour and pain regulation
Authors: Johnson Katerina V. A. , Burnet Philip W. J.
Published: July 2020

Background

Recent research has revealed that the community of microorganisms inhabiting the gut affects brain development, function and behaviour. In particular, disruption of the gut microbiome during critical developmental windows can have lasting effects on host physiology. Both antibiotic exposure and germ-free conditions impact the central nervous system and can alter multiple aspects of behaviour. Social impairments are typically displayed by antibiotic-treated and germ-free animals, yet there is a lack of understanding of the underlying neurobiological changes. Since the μ-opioid, oxytocin and vasopressin systems are key modulators of mammalian social behaviour, here we investigate the effect of experimentally manipulating the gut microbiome on the expression of these pathways.

Results

We show that social neuropeptide signalling is disrupted in germ-free and antibiotic-treated mice, which may contribute to the behavioural deficits observed in these animal models. The most notable finding is the reduction in neuroreceptor gene expression in the frontal cortex of mice administered an antibiotic cocktail post-weaning. Additionally, the changes observed in germ-free mice were generally in the opposite direction to the antibiotic-treated mice.

Conclusions

Antibiotic treatment when young can impact brain signalling pathways underpinning social behaviour and pain regulation. Since antibiotic administration is common in childhood and adolescence, our findings highlight the potential adverse effects that antibiotic exposure during these key neurodevelopmental periods may have on the human brain, including the possible increased risk of neuropsychiatric conditions later in life. In addition, since antibiotics are often considered a more amenable alternative to germ-free conditions, our contrasting results for these two treatments suggest that they should be viewed as distinct models.
The fraction of nitrous oxide in oxygen for facilitating lung collapse during one-lung ventilation with double lumen tube
Authors: Liang Chao , Lv Yuechang , Shi Yu , Cang Jing , Miao Changhong
Published: July 2020

Background

The ideal fraction of nitrous oxide (N2O) in oxygen (O2) for rapid lung collapse remains unclear. Accordingly, this prospective trial aimed to determine the 50% effective concentration (EC50) and 95% effective concentration (EC95) of N2O in O2 for rapid lung collapse.

Methods

This study included 38 consecutive patients undergoing video-assisted thoracoscopic surgery (VATS). The lung collapse score (LCS) of each patient during one-lung ventilation was evaluated by the same surgeon. The first patient received 30% N2O in O2, and the subsequent N2O fraction in O2 was determined by the LCS of the previous patient using the Dixon up-and-down method. The testing interval was set at 10%, and the lowest concentration was 10% (10, 20, 30, 40%, or 50%). The EC50 and EC95 of N2O in O2 for rapid lung collapse were analyzed using a probit test.

Results

According to the up-and-down method, the N2O fraction in O2 at which all patients exhibited successful lung collapse was 50%. The EC50 and EC95 of N2O in O2 for rapid lung collapse were 27.7% (95% confidence interval 19.9–35.7%) and 48.7% (95% confidence interval 39.0–96.3%), respectively.

Conclusions

In patients undergoing VATS, the EC50 and EC95 of N2O in O2 for rapid lung collapse were 27.7 and 48.7%, respectively.

Trial registration

http://www.chictr.org/cn/ Identifier ChiCTR19 00021474, registered on 22 February 2019.
Transcatheter closure of a residual shunt with posteroinferior deficient rim after surgical closure of an ASD: a case report
Authors: Deng Xicheng , Yao Taoyue , Wang Yefeng , Yang Guangxian , Chen Wenjuan , Huang Peng , Chen Zhi
Published: July 2020

Background

There are few reports in the literature of device closure of residual shunts following initial surgical closure of an atrial septal defect (ASD). This case study reports one such case. We describe here a case of secundum type ASD that was initially closed surgically, followed by device closure of a residual shunt with a posteroinferior deficient rim.

Case presentation

A 7-month-old boy was admitted to our hospital for elective surgery to surgically correct a secundum type ASD. Unfortunately, a residual shunt 3.5 mm in diameter appeared before discharge and was enlarged at1-year follow-up. The cause of this residual shunt was dehiscence at the posteroinferior aspect, and the posteroinferior rim was 3.7 mm. After careful discussion and preparation, we proceeded with an interventional procedure. A 16 mm ASD occluder (AGA Medical Corp, Plymouth, Minnesota) was deployed successfully with no residual shunt. In some cases of ASD, interventional therapy is not considered due to the size and position of the defect, but we show here, a successful case of interventional therapy for a residual shunt with a deficient rim.

Conclusion

We have presented a case in which a postoperative residual shunt with a deficient rim was successfully closed with interventional therapy.
A novel method for controlling unobserved confounding using double confounders
Authors: Liu Lu , Hou Lei , Yu Yuanyuan , Liu Xinhui , Sun Xiaoru , Yang Fan , Wang Qing , Jing Ming , Xu Yeping , Li Hongkai , Xue Fuzhong
Published: July 2020

Background

Controlling unobserved confounding still remains a great challenge in observational studies, and a series of strict assumptions of the existing methods usually may be violated in practice. Therefore, it is urgent to put forward a novel method.

Methods

We are interested in the causal effect of an exposure on the outcome, which is always confounded by unobserved confounding. We show that, the causal effect of an exposure on a continuous or categorical outcome is nonparametrically identified through only two independent or correlated available confounders satisfying a non-linear condition on the exposure. Asymptotic theory and variance estimators are developed for each case. We also discuss an extension for more than two binary confounders.

Results

The simulations show better estimation performance by our approach in contrast to the traditional regression approach adjusting for observed confounders. A real application is separately applied to assess the effects of Body Mass Index (BMI) on Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Fasting Blood Glucose (FBG), Triglyceride (TG), Total Cholesterol (TC), High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL) with individuals in Shandong Province, China. Our results suggest that SBP increased 1.60 (95% CI: 0.99–2.93) mmol/L with per 1- kg/m2 higher BMI and DBP increased 0.37 (95% CI: 0.03–0.76) mmol/L with per 1- kg/m2 higher BMI. Moreover, 1- kg/m2 increase in BMI was causally associated with a 1.61 (95% CI: 0.96–2.97) mmol/L increase in TC, a 1.66 (95% CI: 0.91–55.30) mmol/L increase in TG and a 2.01 (95% CI: 1.09–4.31) mmol/L increase in LDL. However, BMI was not causally associated with HDL with effect value − 0.20 (95% CI: − 1.71–1.44). And, the effect value of FBG per 1- kg/m2 higher BMI was 0.56 (95% CI: − 0.24–2.18).

Conclusions

We propose a novel method to control unobserved confounders through double binary confounders satisfying a non-linear condition on the exposure which is easy to access.
Acute duodenal obstruction secondary to intussusception caused by the duodenal diverticulum: a case report
Authors: Guo Yuchen , Liu Bin , Pan Ziwen , Zhang Yang
Published: July 2020

Background

The duodenal intussusception is rarely reported and usually occurs secondary to organic diseases of the duodenum such as polyps, tumors and duplication cysts. Herein we report a case of duodenal intussusception caused by duodenal diverticulum.

Case presentation

A 21-year old male patient presented with abdominal pain and vomiting for one day. A contrast enhanced computed tomography of the abdomen revealed duodenal intussusception. On emergency laparotomy, the intussusception had reduced spontaneously while an invaginated diverticulum was seen at the junction of the descending and horizontal segments of the duodenum. The diverticulum was resected and the patient had uneventful recovery.

Conclusion

Duodenal intussusception is a rare complication of duodenal diverticulum. Being aware of this complication of diverticulum can help in timely diagnosis and treatment.
Conidiobolus pachyzygosporus invasive pulmonary infection in a patient with acute myeloid leukemia: case report and review of the literature
Authors: Stavropoulou E. , Coste A. T. , Beigelman-Aubry C. , Letovanec I. , Spertini O. , Lovis A. , Krueger T. , Burger R. , Bochud P. Y. , Lamoth F.
Published: July 2020

Background

Conidiobolus spp. (mainly C. coronatus) are the causal agents of rhino-facial conidiobolomycosis, a limited soft tissue infection, which is essentially observed in immunocompetent individuals from tropical areas. Rare cases of invasive conidiobolomycosis due to C. coronatus or other species (C.incongruus, C.lamprauges) have been reported in immunocompromised patients. We report here the first case of invasive pulmonary fungal infection due to Conidiobolus pachyzygosporus in a Swiss patient with onco-haematologic malignancy.

Case presentation

A 71 year-old female was admitted in a Swiss hospital for induction chemotherapy of acute myeloid leukemia. A chest CT performed during the neutropenic phase identified three well-circumscribed lung lesions consistent with invasive fungal infection, along with a positive 1,3-beta-d-glucan assay in serum. A transbronchial biopsy of the lung lesions revealed large occasionally septate hyphae. A Conidiobolus spp. was detected by direct 18S rDNA in the tissue biopsy and subsequently identified at species level as C. pachyzygosporus by 28S rDNA sequencing. The infection was cured after isavuconazole therapy, recovery of the immune system and surgical resection of lung lesions.

Conclusions

This is the first description of C. pachyzygosporus as human pathogen and second case report of invasive conidiobolomycosis from a European country.
Spatial-temporal analysis of tuberculosis in Chongqing, China 2011-2018
Authors: Yu Ya , Wu Bo , Wu Chengguo , Wang Qingya , Hu Daiyu , Chen Wei
Published: July 2020

Background

China is a country with a high burden of pulmonary tuberculosis (PTB). Chongqing is in the southwest of China, where the notification rate of PTB ranks tenth in China. This study analyzed the temporal and spatial distribution characteristics of PTB in Chongqing in order to improve TB control measures.

Methods

A spatial-temporal analysis has been performed based on the data of PTB from 2011 to 2018, which was extracted from the National Surveillance System. The effect of TB control was measured by variation trend of pathogenic positive PTB notification rate and total TB notification rate. Time series, spatial autonomic correlation and spatial-temporal scanning methods were used to identify the temporal trends and spatial patterns at county level.

Results

A total of 188,528 cases were included in this study. A downward trend was observed in PTB between 2011 and 2018 in Chongqing. The peak of PTB notification occurred in late winter and early spring annually. By calculating the value of Global Moran’s I and Local Getis’s Gi*, we found that PTB was spatially clustered and some significant hot spots were detected in the southeast and northeast of Chongqing. One most likely cluster and three secondary clusters were identified by Kulldorff’s scan spatial-temporal Statistic.

Conclusions

This study identified seasonal patterns and spatial-temporal clusters of PTB cases in Chongqing. Priorities should be given to southeast and northeast of Chongqing for better TB control.
Occurrence of septuple and elevated Pfdhfr-Pfdhps quintuple mutations in a general population threatens the use of sulfadoxine-pyrimethamine for malaria prevention during pregnancy in eastern-coast of Tanzania
Authors: Bwire George M. , Mikomangwa Wigilya P. , Kilonzi Manase
Published: July 2020

Background

Plasmodium falciparumdihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) mutations compromise the effectiveness of sulfadoxine-pyrimethamine (SP) for treatment of uncomplicated malaria, and are likely to impair the efficiency of intermittent preventive treatment during pregnancy (IPTp). This study was conducted to determine the level ofPfdhfr-Pfdhpsmutations, a decade since SP was limited for IPTp use in pregnant women in Tanzania.

Methods

P. falciparumgenomic DNA was extracted from dried blood spots prepared from a finger prick. Extracted DNA were sequenced using a single MiSeq lane by combining all PCR products. Genotyping ofPfdhfrandPfdhpsmutations were done using bcftools whereas custom scripts were used to filter and translate genotypes into SP resistance haplotypes.

Results

ThePfdhfrwas analyzed from 445 samples, the wild type (WT)Pfdhfrhaplotype NCSI was detected in 6 (1.3%) samples. TriplePfdhfrIRNI (mutations are bolded and underlined) haplotype was dominant, contributing to 84% (number [n] = 374) of haplotypes while 446 samples were studied forPfdhps, WT forPfdhps(SAKAA) was found in 6.7% (n = 30) in samples. DoublePfdhpshaplotype (SGEAA) accounted for 83% of all mutations atPfdhpsgene. Of 447Pfdhfr-Pfdhpscombined genotypes, only 0.9% (n = 4) samples contained WT gene (SAKAA-NCSI). Quintuple (five) mutations, SGEAA-IRNI accounted for 71.4% (n = 319) whereas 0.2% (n = 1) had septuple (seven) mutations (AGKGS-IRNI). The overall prevalence ofPfdhfrK540E was 90.4% (n = 396) whilePfdhpsA581G was 1.1% (n = 5).

Conclusions

This study found high prevalence ofPfdhfr–Pfdhpsquintuple and presence of septuple mutations. Mutations atPfdhfrK540E andPfdhpsA581G, major predictors for IPTp-SP failure were within the recommended WHO range. Abandonment of IPTp-SP is recommended in settings where thePfdhfrK540E prevalence is > 95% andPfdhpsA581G is > 10% as SP is likely to be not effective. Nonetheless, saturation inPfdhfrandPfdhpshaplotypes is alarming, a search for alternative antimalarial drug for IPTp in the study area is recommended.
Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa
Authors: Naicker Cherise L. , Mansoor Leila E. , Dawood Halima , Naidoo Kogieleum , Singo Denzhe , Matten David , Williamson Carolyn , Abdool Karim Quarraisha
Published: July 2020

Background

The World Health Organisation recommends the use of tenofovir-containing pre-exposure prophylaxis (PrEP) as an additional Human Immunodeficiency Virus (HIV) prevention choice for men and women at substantial risk of HIV infection. PrEP could fill an important HIV prevention gap, especially for sexually active young women who are limited in their ability to negotiate mutual monogamy or condom use.

As PrEP is scaled up in high HIV incidence settings, it is crucial to consider the importance of early identification of HIV infection during PrEP use, to allow for rapid discontinuation of PrEP to reduce the risk of antiretroviral (ARV) resistance. The purpose of this case study is to provide this critical evidence.

Case presentation

This report describes a 20-year-old woman in a HIV sero-discordant relationship who initiated oral PrEP (tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC)) through a demonstration project (CAPRISA 084) in October 2017. Despite good adherence throughout her PrEP use, she tested HIV antibody positive at month nine of study participation.

Retrospective testing showed increasing HIV viral load over time, and retrospective use of fourth-generation rapid HIV tests showed HIV detection (positive antigen/antibody) at month one. Sequencing confirmed a dominant wild type at month one with dual therapy resistance patterns emerging by month three (M184V and K65R mutations), which is suggestive of protracted PrEP use during an undetected HIV infection.

The participant was referred to infectious diseases for further management of her HIV infection and was initiated on a first line, tenofovir-sparing regimen. At the time of this report (January 2020), the participant had been on ARV- therapy (ART) for 13 months and had no signs of either clinical, immunologic or virologic failure.

Conclusions

This case report highlights the importance of appropriate HIV screening during wider oral PrEP scale-up in high HIV incidence settings to circumvent the consequences of prolonged dual therapy in an undiagnosed HIV infection and in turn prevent ARV resistance.
Characterization of putative drug resistant biomarkers in Plasmodium falciparum isolated from Ghanaian blood donors
Authors: Aninagyei Enoch , Duedu Kwabena Obeng , Rufai Tanko , Tetteh Comfort Dede , Chandi Margaretta Gloria , Ampomah Paulina , Acheampong Desmond Omane
Published: July 2020

Background

Plasmodium falciparum parasites, which could harbour anti-malaria drug resistance genes, are commonly detected in blood donors in malaria-endemic areas. Notwithstanding, anti-malaria drug resistant biomarkers have not been characterized in blood donors with asymptomatic P. falciparum infection.

Methods

A total of 771 blood donors were selected from five districts in the Greater Accra Region, Ghana. Each donor sample was screened with malaria rapid diagnostic test (RDT) kit and parasitaemia quantified microscopically. Dried blood spots from malaria positive samples were genotyped for P. falciparum chloroquine resistance transporter (Pfcrt), P. falciparum multi-drug resistance (Pfmdr1), P. falciparum dihydropteroate-synthetase (Pfdhps), P. falciparum dihydrofolate-reductase (Pfdhfr) and Kelch 13 propeller domain on chromosome 13 (Kelch 13) genes.

Results

Of the 771 blood donors, 91 (11.8%) were positive by RDT. Analysis of sequence reads indicated successful genotyping of Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes in 84.6, 81.3, 86.8, 86.9 and 92.3% of the isolates respectively. Overall, 21 different mutant haplotypes were identified in 69 isolates (75.8%). In Pfcrt, CVIET haplotype was observed in 11.6% samples while in Pfmdr1, triple mutation (resulting in YFN haplotype) was detected in 8.1% of isolates. In Pfdhfr gene, triple mutation resulting in IRNI haplotype and in Pfdhps gene, quintuple mutation resulting in AGESS haplotype was identified in 17.7% parasite isolates. Finally, five non-synonymous Kelch 13 alleles were detected; C580Y (3.6%), P615L (4.8%), A578S (4.8%), I543V (2.4%) and A676S (1.2%) were detected.

Conclusion

Results obtained in this study indicated various frequencies of mutant alleles in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes from P. falciparum infected blood donors. These alleles could reduce the efficacy of standard malaria treatment in transfusion-transmitted malaria cases. Incorporating malaria screening into donor screening protocol to defer infected donors is therefore recommended.
An improved deep learning approach and its applications on colonic polyp images detection
Authors: Wang Wei , Tian Jinge , Zhang Chengwen , Luo Yanhong , Wang Xin , Li Ji
Published: July 2020

Background

Colonic polyps are more likely to be cancerous, especially those with large diameter, large number and atypical hyperplasia. If colonic polyps cannot be treated in early stage, they are likely to develop into colon cancer. Colonoscopy is easily limited by the operator’s experience, and factors such as inexperience and visual fatigue will directly affect the accuracy of diagnosis. Cooperating with Hunan children’s hospital, we proposed and improved a deep learning approach with global average pooling (GAP) in colonoscopy for assisted diagnosis. Our approach for assisted diagnosis in colonoscopy can prompt endoscopists to pay attention to polyps that may be ignored in real time, improve the detection rate, reduce missed diagnosis, and improve the efficiency of medical diagnosis.

Methods

We selected colonoscopy images from the gastrointestinal endoscopy room of Hunan children’s hospital to form the colonic polyp datasets. And we applied the image classification method based on Deep Learning to the classification of Colonic Polyps. The classic networks we used are VGGNets and ResNets. By using global average pooling, we proposed the improved approaches: VGGNets-GAP and ResNets-GAP.

Results

The accuracies of all models in datasets exceed 98%. The TPR and TNR are above 96 and 98% respectively. In addition, VGGNets-GAP networks not only have high classification accuracies, but also have much fewer parameters than those of VGGNets.

Conclusions

The experimental results show that the proposed approach has good effect on the automatic detection of colonic polyps. The innovations of our method are in two aspects: (1) the detection accuracy of colonic polyps has been improved. (2) our approach reduces the memory consumption and makes the model lightweight. Compared with the original VGG networks, the parameters of our VGG19-GAP networks are greatly reduced.
Severe syndromic ID and skewed X-inactivation in a girl with NAA10 dysfunction and a novel heterozygous de novo NAA10 p.(His16Pro) variant - a case report
Authors: Bader Ingrid , McTiernan Nina , Darbakk Christine , Boltshauser Eugen , Ree Rasmus , Ebner Sabine , Mayr Johannes A. , Arnesen Thomas
Published: July 2020

Background

NAA10 is the catalytic subunit of the major N-terminal acetyltransferase complex NatA which acetylates almost half the human proteome. Over the past decade, many NAA10 missense variants have been reported as causative of genetic disease in humans. Individuals harboring NAA10 variants often display variable degrees of intellectual disability (ID), developmental delay, and cardiac anomalies. Initially, carrier females appeared to be oligo- or asymptomatic with X-inactivation pattern skewed towards the wild type allele. However, recently it has been shown that NAA10 variants can cause syndromic or non-syndromic intellectual disability in females as well. The impact of specific NAA10 variants and the X-inactivation pattern on the individual phenotype in females remains to be elucidated.

Case presentation

Here we present a novel de novo NAA10 (NM_003491.3) c.[47A > C];[=] (p.[His16Pro];[=]) variant identified in a young female. The 10-year-old girl has severely delayed motor and language development, disturbed behavior with hyperactivity and restlessness, moderate dilatation of the ventricular system and extracerebral CSF spaces. Her blood leukocyte X-inactivation pattern was skewed (95/5) towards the maternally inherited X-chromosome. Our functional study indicates that NAA10 p.(H16P) impairs NatA complex formation and NatA catalytic activity, while monomeric NAA10 catalytic activity appears to be intact. Furthermore, cycloheximide experiments show that the NAA10 H16P variant does not affect the cellular stability of NAA10.

Discussion and conclusions

We demonstrate that NAA10 p.(His16Pro) causes a severe form of syndromic ID in a girl most likely through impaired NatA-mediated Nt-acetylation of cellular proteins. X-inactivation analyses showed a skewed X-inactivation pattern in DNA from blood of the patient with the maternally inherited allele being preferentially methylated/inactivated.
Risk of chronic kidney disease in patients with kidney stones—a nationwide cohort study
Authors: Chuang Tzung-Fang , Hung Hung-Chang , Li Shu-Fen , Lee Mei-Wen , Pai Jar-Yuan , Hung Chin-Tun
Published: July 2020

Background

Chronic kidney disease (CKD) and kidney stones are common in Taiwan; in particular, CKD has a high prevalence but low self-awareness rate. CKD-related risk factors such as diabetes, hypertension, and nephrotoxic drugs are well-known and uncontested; however, kidney stones are relatively less studied and easily overlooked as a risk factor. The objective of this study was to investigate whether kidney stones are a risk factor for CKD.

Methods

We conducted a nationwide population-based matched cohort study to assess the risk of incident CKD in people with kidney stones. Data on incident stones formers in the year 2001—excluding those with a history of CKD—were obtained from Taiwan’s National Health Insurance database. Stone formers were matched (1:4) to control subjects according to sex, age, and index date. The total observation period of the study was 10 years, and the primary end-point was the occurrence of CKD. Student’s t-test and Chi-squared test were used to compare continuous and categorical data, respectively. Logistic regression was used to calculate the odds ratio of kidney stone patients with incident CKD relative to the control group. Cox proportional hazard regression model was used to obtain the hazard ratio for development of incident CKD among patients with kidney stones.

Results

The incidence of CKD in the kidney stone cohort was 11.2%, which was significantly higher than that of the control group (P < .001). Survival analysis showed that the stones cohort was 1.82 times more likely to experience CKD than the controls. Age, sex, hypertension, diabetes mellitus, and hyperlipidemia increased the risk of CKD incidence (1.04, 1.27, 1.55, 3.31, and 1.25 times, respectively).

Conclusion

Kidney stones are a definite risk factor for CKD; therefore, patients with stones are suggested to undergo regular renal function monitoring and receive appropriate treatment to avoid CKD.
Efficacy of different urinary uric acid indicators in patients with chronic kidney disease
Authors: Guan Haochen , Zheng Yuqi , Zhou Xun , Xu Ying , Fu Chensheng , Xiao Jing , Ye Zhibin
Published: July 2020

Background

Mounting studies have shown that hyperuricemia is related to kidney diseases through multiple ways. However, the application of urinary uric acid indicators in patients with reduced renal function is not clear. In this study, we aim to determine the effects of renal function on various indicators reflecting uric acid levels in patients with chronic kidney disease (CKD).

Methods

Anthropometric and biochemical examinations were performed in 625 patients with CKD recruited from Dept of Nephrology of Huadong hospital affiliated to Fudan University. Multiple regression analyses were used to study correlations of the estimated glomerular filtration rate (eGFR) with serum uric acid (SUA) and renal handling of uric acid. For further study, smooth curve plots and threshold effect analyses were applied to clarify associations between renal function and uric acid levels.

Results

The nonlinear relationships were observed between eGFR and urinary uric acid indicators. The obvious inflection points were observed in smooth curve fitting of eGFR and fractional excretion of uric acid (FEur), excretion of uric acid per volume of glomerular filtration (EurGF). In subsequent analyses where levels of eGFR< 15 mL/min/1.73m2 were dichotomized (CKD5a/CKD5b), patients in the CKD5a showed higher levels of FEur and EurGF while lower levels of urinary uric acid excretion (UUA), clearance of uric acid (Cur) and glomerular filtration load of uric acid (FLur) compared with CKD5b group (all P < 0.05). And there was no significant difference of SUA levels between two groups. On the other hand, when eGFR< 109.9 ml/min/1.73 m2 and 89.1 ml/min/1.73 m2, the resultant curves exhibited approximately linear associations of eGFR with Cur and FLur respectively.

Conclusion

FEur and EurGF showed significantly compensatory increases with decreased renal function. And extra-renal uric acid excretion may play a compensatory role in patients with severe renal impairment to maintain SUA levels. Moreover, Cur and FLur may be more reliable indicators of classification for hyperuricemia in CKD patients.
RETRACTED ARTICLE: Invasion inhibition in pancreatic cancer using the oral iron chelating agent deferasirox
Authors: Amano Shogo , Kaino Seiji , Shinoda Shuhei , Harima Hirofumi , Matsumoto Toshihiko , Fujisawa Koichi , Takami Taro , Yamamoto Naoki , Yamasaki Takahiro , Sakaida Isao
Published: July 2020

Background

Iron is required for cellular metabolism, and rapidly proliferating cancer cells require more of this essential nutrient. Therefore, iron regulation may well represent a new avenue for cancer therapy. We have reported, through in vitro and in vivo research involving pancreatic cancer cell lines, that the internal-use, next-generation iron chelator deferasirox (DFX) exhibits concentration-dependent tumour-suppressive effects, among other effects. After performing a microarray analysis on the tumour grafts used in that research, we found that DFX may be able to suppress the cellular movement pathways of pancreatic cancer cells. In this study, we conducted in vitro analyses to evaluate the effects of DFX on the invasive and migratory abilities of pancreatic cancer cells.

Methods

We used pancreatic cancer cell lines (BxPC-3, Panc-1, and HPAF II) to examine the efficacy of DFX in preventing invasion in vitro, evaluated using scratch assays and Boyden chamber assays. In an effort to understand the mechanism of action whereby DFX suppresses tumour invasion and migration, we performed G-LISA to examine the activation of Cdc42 and Rac1 which are known for their involvement in cellular movement pathways.

Results

In our scratch assays, we observed that DFX-treated cells had significantly reduced invasive ability compared with that of control cells. Similarly, in our Boyden chamber assays, we observed that DFX-treated cells had significantly reduced migratory ability. After analysis of the Rho family of proteins, we observed a significant reduction in the activation of Cdc42 and Rac1 in DFX-treated cells.

Conclusions: DFX can suppress the motility of cancer cells by reducing Cdc42 and Rac1 activation. Pancreatic cancers often have metastatic lesions, which means that use of DFX will suppress not only tumour proliferation but also tumour invasion, and we expect that this will lead to improved prognoses.