bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of interactive biological web applications with R/Shiny
Authors: Jia Lihua , Yao Wen , Jiang Yingru , Li Yang , Wang Zhizhan , Li Haoran , Huang Fangfang , Li Jiaming , Chen Tiantian , Zhang Huiyong
Published: September 2021

Development of interactive web applications to deposit, visualize and analyze biological datasets is a major subject of bioinformatics. R is a programming language for data science, which is also one of the most popular languages used in biological data analysis and bioinformatics. However, building interactive web applications was a great challenge for R users before the Shiny package was developed by the RStudio company in 2012. By compiling R code into HTML, CSS and JavaScript code, Shiny has made it incredibly easy to build web applications for the large R community in bioinformatics and for even non-programmers. Over 470 biological web applications have been developed with R/Shiny up to now. To further promote the utilization of R/Shiny, we reviewed the development of biological web applications with R/Shiny, including eminent biological web applications built with R/Shiny, basic steps to build an R/Shiny application, commonly used R packages to build the interface and server of R/Shiny applications, deployment of R/Shiny applications in the cloud and online resources for R/Shiny.
Sensitive, reliable and robust circRNA detection from RNA-seq with CirComPara2
Authors: Gaffo Enrico , Buratin Alessia , Dal Molin Anna , Bortoluzzi Stefania
Published: September 2021

Circular RNAs (circRNAs) are a large class of covalently closed RNA molecules originating by a process called back-splicing. CircRNAs are emerging as functional RNAs involved in the regulation of biological processes as well as in disease and cancer mechanisms. Current computational methods for circRNA identification from RNA-seq experiments are characterized by low discovery rates and performance dependent on the analysed data set. We developed CirComPara2 (https://github.com/egaffo/CirComPara2), a new automated computational pipeline for circRNA discovery and quantification, which consistently achieves high recall rates without losing precision by combining multiple circRNA detection methods. In our benchmark analysis, CirComPara2 outperformed state-of-the-art circRNA discovery tools and proved to be a reliable and robust method for comprehensive transcriptome characterization.
echolocatoR: an automated end-to-end statistical and functional genomic fine-mapping pipeline
Authors: Schilder Brian M , Humphrey Jack , Raj Towfique
Published: September 2021

echolocatoR integrates a diverse suite of statistical and functional fine-mapping tools to identify, test enrichment in, and visualize high-confidence causal consensus variants in any phenotype. It requires minimal input from users (a summary statistics file), can be run in a single R function, and provides extensive access to relevant datasets (e.g. reference linkage disequilibrium panels, quantitative trait loci, genome-wide annotations, cell-type-specific epigenomics), thereby enabling rapid, robust and scalable end-to-end fine-mapping investigations.

Availability and implementation

echolocatoR is an open-source R package available through GitHub under the GNU General Public License (Version 3) license: https://github.com/RajLabMSSM/echolocatoR.

Supplementary information

Supplementary data are available at Bioinformatics online.
Comparing mRNA and sncRNA profiles during the maternal-to-embryonic transition in bovine IVF and scNT embryos
Authors: Cuthbert Jocelyn M , Russell Stewart J , Polejaeva Irina A , Meng Qinggang , White Kenneth L , Benninghoff Abby D
Published: September 2021

Production of embryos with high developmental competence by somatic cell nuclear transfer (scNT) is far less efficient than for in vitro fertilized (IVF) embryos, likely due to an accumulation of errors in genome reprogramming that results in aberrant expression of RNA transcripts, including messenger RNAs (mRNA) and, possibly, microRNAs (miRNA). Thus, our objectives were to use RNAseq to determine the dynamics of mRNA expression in early developing scNT and IVF embryos in the context of the maternal-to-embryonic transition (MET) and to correlate apparent transcriptional dysregulation in cloned embryos with miRNA expression profiles. Comparisons between scNT and IVF embryos indicated large scale transcriptome differences, which were most evident at the 8-cell and morula stages for genes associated with biological functions critical for the MET. For two miRNAs previously identified as differentially expressed in scNT morulae, miR-34a and miR-345, negative correlations with some predicted mRNA targets were apparent, though not widespread among the majority of predicted targets. Moreover, although large-scale aberrations in expression of mRNAs were evident during the MET in cattle scNT embryos, these changes were not consistently correlated with aberrations in miRNA expression at the same developmental stage, suggesting that other mechanisms controlling gene expression may be involved.
Genome activation in equine in vitro–produced embryos
Authors: Goszczynski D E , Tinetti P S , Choi Y H , Hinrichs K , Ross P J
Published: September 2021

Embryonic genome activation is a critical event in embryo development, in which the transcriptional program of the embryo is initiated. The timing and regulation of this process are species-specific. In vitro embryo production is becoming an important clinical and research tool in the horse; however, very little is known about genome activation in this species. The objective of this work was to identify the timing of genome activation, and the transcriptional networks involved, in in vitro–produced horse embryos. RNA-Seq was performed on oocytes and embryos at eight stages of development (MII, zygote, 2-cell, 4-cell, 8-cell, 16-cell, morula, blastocyst; n = 6 per stage, 2 from each of 3 mares). Transcription of seven genes was initiated at the 2-cell stage. The first substantial increase in gene expression occurred at the 4-cell stage (minor activation), followed by massive gene upregulation and downregulation at the 8-cell stage (major activation). An increase in intronic nucleotides, indicative of transcription initiation, was also observed at the 4-cell stage. Co-expression network analyses identified groups of genes that appeared to be regulated by common mechanisms. Investigation of hub genes and binding motifs enriched in the promoters of co-expressed genes implicated several transcription factors. This work represents, to the best of our knowledge, the first genomic evaluation of embryonic genome activation in horse embryos.
Allele-specific expression analysis reveals conserved and unique features of preimplantation development in equine ICSI embryos
Authors: Goszczynski D E , Tinetti P S , Choi Y H , Ross P J , Hinrichs K
Published: September 2021

Embryonic genome activation and dosage compensation are major genetic events in early development. Combined analysis of single embryo RNA-seq data and parental genome sequencing was used to evaluate parental contributions to early development and investigate X-chromosome dynamics. In addition, we evaluated dimorphism in gene expression between male and female embryos. Evaluation of parent-specific gene expression revealed a minor increase in paternal expression at the 4-cell stage that increased at the 8-cell stage. We also detected eight genes with allelic expression bias that may have an important role in early development, notably NANOGNB. The main actor in X-chromosome inactivation, XIST, was significantly upregulated at the 8-cell, morula, and blastocyst stages in female embryos, with high expression at the latter. Sexual dimorphism in gene expression was identified at all stages, with strong representation of the X-chromosome in females from the 16-cell to the blastocyst stage. Female embryos showed biparental X-chromosome expression at all stages after the 4-cell stage, demonstrating the absence of imprinted X-inactivation at the embryo level. The analysis of gene dosage showed incomplete dosage compensation (0.5 < X:A < 1) in MII oocytes and embryos up to the 4-cell stage, an increase of the X:A ratio at the 16-cell and morula stages after genome activation, and a decrease of the X:A ratio at the blastocyst stage, which might be associated with the beginning of X-chromosome inactivation. This study represents the first critical analysis of parent- and sex-specific gene expression in early equine embryos produced in vitro.
‘I Married a Gay Man’: Tongqi’s Agency in Marital Decisions
Authors: Zhou Yao , Xie Hui , Song Changhui
Published: September 2021

There has been an increasing interest in the ‘tongqi phenomenon’ in China. The ‘tongqi phenomenon’ is usually described in research as mixed-orientation marriages (MOMs). Tongqi refers to a group of heterosexual women who unwittingly married non-straight men. While the literature on the ‘tongqi phenomenon’ has mainly focused on the adverse effects and victimisation on tongqi, this qualitative study aimed to understand how tongqi construct their reality/perplexity within a MOM on how they determined conjugal relationships after discovering their husband’s sexual orientation. We adopted the virtual ethnography method to conduct non-participant observation in the tongqi online support group, followed by fourteen semi-structured, in-depth interviews in China. Three main themes emerged via thematic analysis: maintaining the intact marriage, reframing their marriage and getting a divorce. Tongqi showed agency and resilience in understanding their marital situations, navigating resources and making marital life fit their reality. The practical implications for social work and future studies are discussed.
Multimodal mechanisms of human socially reinforced learning across neurodegenerative diseases
Authors: Legaz Agustina , Abrevaya Sofía , Dottori Martín , González Campo Cecilia , Birba Agustina , Martorell Caro Miguel , Aguirre Julieta , Slachevsky Andrea , Aranguiz Rafael , Serrano Cecilia , Gillan Claire M , Leroi Iracema , García Adolfo M , Fittipaldi Sol , Ibañez Agustín
Published: September 2021

Social feedback can selectively enhance learning in diverse domains. Relevant neurocognitive mechanisms have been studied mainly in healthy persons, yielding correlational findings. Neurodegenerative lesion models, coupled with multimodal brain measures, can complement standard approaches by revealing direct multidimensional correlates of the phenomenon.

To this end, we assessed socially reinforced and non-socially reinforced learning in 40 healthy participants as well as persons with behavioural variant frontotemporal dementia (n = 21), Parkinson’s disease (n = 31) and Alzheimer’s disease (n = 20). These conditions are typified by predominant deficits in social cognition, feedback-based learning and associative learning, respectively, although all three domains may be partly compromised in the other conditions. We combined a validated behavioural task with ongoing EEG signatures of implicit learning (medial frontal negativity) and offline MRI measures (voxel-based morphometry).

In healthy participants, learning was facilitated by social feedback relative to non-social feedback. In comparison with controls, this effect was specifically impaired in behavioural variant frontotemporal dementia and Parkinson’s disease, while unspecific learning deficits (across social and non-social conditions) were observed in Alzheimer’s disease. EEG results showed increased medial frontal negativity in healthy controls during social feedback and learning. Such a modulation was selectively disrupted in behavioural variant frontotemporal dementia. Neuroanatomical results revealed extended temporo-parietal and fronto-limbic correlates of socially reinforced learning, with specific temporo-parietal associations in behavioural variant frontotemporal dementia and predominantly fronto-limbic regions in Alzheimer’s disease. In contrast, non-socially reinforced learning was consistently linked to medial temporal/hippocampal regions. No associations with cortical volume were found in Parkinson’s disease. Results are consistent with core social deficits in behavioural variant frontotemporal dementia, subtle disruptions in ongoing feedback-mechanisms and social processes in Parkinson’s disease and generalized learning alterations in Alzheimer’s disease. This multimodal approach highlights the impact of different neurodegenerative profiles on learning and social feedback.

Our findings inform a promising theoretical and clinical agenda in the fields of social learning, socially reinforced learning and neurodegeneration.
Short- and Long-term Outcomes of Group B Streptococcus Invasive Disease in Mozambican Children: Results of a Matched Cohort and Retrospective Observational Study and Implications for Future Vaccine Introduction
Authors: Bramugy Justina , Mucasse Humberto , Massora Sergio , Vitorino Pio , Aerts Céline , Mandomando Inacio , Paul Proma , Chandna Jaya , Seedat Farah , Lawn Joy E , Bardají Azucena , Bassat Quique
Published: September 2021

Background

Invasive group B Streptococcus disease (iGBS) in infancy, including meningitis or sepsis, carries a high risk of mortality and neurodevelopmental impairment (NDI). We present data on iGBS from 2 decades of surveillance in Manhiça, Mozambique, with a focus on NDI.

Methods

Morbidity surveillance databases in a rural Mozambican district hospital were screened for iGBS cases. From February 2020 to March 2021, surviving iGBS patients (n = 39) plus age- and sex-matched children without iGBS (n = 119) were assessed for neurocognitive development, vision, and hearing. The role of GBS in stillbirths and infant deaths was investigated using minimally invasive tissue sampling (MITS).

Results

Ninety iGBS cases were included, with most children being <3 months of age (85/90). The in-hospital case fatality rate was 14.4% (13/90), increasing to 17.8% (3 additional deaths) when considering mortality during the 6 months postdiagnosis. Fifty percent of the iGBS exposed infants and 10% of those unexposed showed any NDI. Surviving GBS conferred a 11-fold increased adjusted odds of moderate/severe NDI (odds ratio, 2.8 [95% confidence interval, .92–129.74]; P = .06) in children aged 0–5 years. For older children (6–18 years), no differences in NDI were found between exposed and unexposed. Motor domain was the most affected among young GBS survivors. Three stillbirths and 4 early neonatal deaths (of the 179 MITS performed) were attributed to iGBS.

Conclusions

In absence of preventive strategies, such as intrapartum antibiotics, iGBS remains a significant cause of perinatal and infant disease and death. GBS also causes major longer-term neurodevelopmental sequelae, altogether justifying the need for maternal GBS vaccination strategies to increase perinatal and infant survival.
Effect of Time Since Death on Multipathogen Molecular Test Results of Postmortem Specimens Collected Using Minimally Invasive Tissue Sampling Techniques
Authors: Dawa Jeanette , Walong Edwin , Onyango Clayton , Mathaiya John , Muturi Peter , Bunei Milka , Ochieng Washington , Barake Walter , Seixas Josilene N , Mayieka Lillian , Ochieng Melvin , Omballa Victor , Lidechi Shirley , Hunsperger Elizabeth , Otieno Nancy A , Ritter Jana M , Widdowson Marc-Alain , Diaz Maureen H , Winchell Jonas M , Martines Roosecelis B , Zaki Sherif R , Chaves Sandra S
Published: September 2021

Background

We used postmortem minimally invasive tissue sampling (MITS) to assess the effect of time since death on molecular detection of pathogens among respiratory illness–associated deaths.

Methods

Samples were collected from 20 deceased children (aged 1–59 months) hospitalized with respiratory illness from May 2018 through February 2019. Serial lung and/or liver and blood samples were collected using MITS starting soon after death and every 6 hours thereafter for up to 72 hours. Bodies were stored in the mortuary refrigerator for the duration of the study. All specimens were analyzed using customized multipathogen TaqMan® array cards (TACs).

Results

We identified a median of 3 pathogens in each child’s lung tissue (range, 1–8; n = 20), 3 pathogens in each child’s liver tissue (range, 1–4; n = 5), and 2 pathogens in each child’s blood specimen (range, 0–4; n = 5). Pathogens were not consistently detected across all collection time points; there was no association between postmortem interval and the number of pathogens detected (P = .43) and no change in TAC cycle threshold value over time for pathogens detected in lung tissue. Human ribonucleoprotein values indicated that specimens collected were suitable for testing throughout the study period.

Conclusions

Results suggest that lung, liver, and blood specimens can be collected using MITS procedures up to 4 days after death in adequately preserved bodies. However, inconsistent pathogen detection in samples needs careful consideration before drawing definitive conclusions on the etiologic causes of death.
Quantifying the Acute Care Costs of Neonatal Bacterial Sepsis and Meningitis in Mozambique and South Africa
Authors: Aerts Céline , Leahy Shannon , Mucasse Humberto , Lala Sanjay , Bramugy Justina , Tann Cally J , Madhi Shabir A , Bardají Azucena , Bassat Quique , Dangor Ziyaad , Lawn Joy E , Jit Mark , Procter Simon R
Published: September 2021

Background

Sepsis and meningitis are among the leading causes of neonatal deaths in sub-Saharan Africa (SSA). Neonatal sepsis caused ~400 000 deaths globally in 2015, half occurring in Africa. Despite this, there are few published data on the acute costs of neonatal sepsis or meningitis, with none in SSA.

Methods

We enrolled neonates admitted to 2 hospitals in South Africa and Mozambique between 16 April 2020 and 1 April 2021. In South Africa all cases were microbiologically confirmed, but in Mozambique both clinically suspected and microbiologically confirmed cases were included. Data were collected on healthcare resource use and length of stay, along with information on household expenditure and caregiving. We used unit costs of healthcare resources in local currencies to estimate healthcare provider costs per patient and costs per household. Results were converted to 2019 international dollars (I$).

Results

We enrolled 11 neonates in Mozambique and 18 neonates in South Africa. Mean length of stay was 10 days (median, 9 [interquartile range {IQR}, 4–14) and 16 days (median, 15 [IQR, 13–18]), respectively. In Mozambique we estimated mean household costs of I$49.62 (median, 10.19 [IQR, 5.10–95.12]) and hospitalization costs of I$307.58 (median, 275.12 [IQR, 149.43–386.12]). In South Africa these costs were I$52.31 (median, 30.82 [IQR, 19.25–73.08]) and I$684.06 (median, 653.62 [IQR, 543.33–827.53]), respectively.

Conclusions

We found substantial costs associated with acute neonatal bacterial (all-cause) sepsis and meningitis in SSA. Our estimates will inform economic evaluations of interventions to prevent neonatal invasive bacterial infections.
Lung Cancer Detection and Severity Level Classification Using Sine Cosine Sail Fish Optimization Based Generative Adversarial Network with CT Images
Authors: Selvapandian A   , Prabhu S Nagendra , Sivakumar P   , Rao D B Jagannadha
Published: September 2021

This paper develops a lung nodule detection mechanism using the proposed sine cosine Sail Fish (SCSF) based generative adversarial network (GAN). However, the proposed SCSF-based GAN is designed by integrating the sine cosine algorithm with the SailFish optimizer, respectively. By using pre-processing, lung nodule segmentation, feature extraction, lung cancer detection, and severity level classification methods detection and classification are performed. The pre-processed computed tomography (CT) image is fed to the lung nodule segmentation phase, where the CT image is segmented into different sub-images to exactly detect the abnormal region. The segmented result after segmentation is fed to the feature extraction phase, where the features like mean, variance, entropy and hole entropy, are extracted from the nodule region. The affected regions are accurately detected using the loss function of the discriminator component. Finally, the lung nodules are detected and classified using the proposed SCSF-based GAN. The proposed approach obtained better performance with the accuracy of 96.925%, sensitivity of 96.900% and specificity of 97.920% for the first-level classification, and the accuracy of 94.987%, the sensitivity of 94.962% and specificity of 95.962% for second-level classification, respectively.
Phenology of Bean Leaf Beetle (Coleoptera: Chrysomelidae) in Ontario, Canada and Field Validation of a Degree-Day Model
Authors: McCreary Cara M , Smith Jocelyn L , Bahlai Christie A , Schaafsma Art W , Hallett Rebecca H
Published: September 2021

The phenology and voltinism of bean leaf beetle, Cerotoma trifurcata (Forster), were examined in three counties in 2010 and two counties in 2011 in Ontario soybean, Glycine max (L.) Merr., fields. Soil samples from within cages containing field-collected beetles revealed one cycle of eggs, larvae, and pupae. Observed degree-day (DD) accumulations for C. trifurcata life stage events (egg hatch, egg hatch to pupation, and oviposition to peak adult) in field experiments were compared with thermal constants determined in a temperature-dependent development laboratory experiment where C. trifurcata were reared under five constant temperatures. Observed and predicted DDs for all life stage events were nearly identical. Mean DD accumulations from first oviposition to peak adult emergence in the field studies was 589 ± 67 DD (base 10.3°C), which was nearly identical to the model prediction (581 ± 40 DD, base 10.3°C).
Obesity modifies the energetic phenotype of dilated cardiomyopathy
Authors: Rayner Jennifer J , Peterzan Mark A , Clarke William T , Rodgers Christopher T , Neubauer Stefan , Rider Oliver J
Published: September 2021

Aims

We sought to determine if myocardial energetics could distinguish obesity cardiomyopathy as a distinct entity from dilated cardiomyopathy.

Methods and results

Sixteen normal weight participants with dilated cardiomyopathy (DCMNW), and 27 with DCM and obesity (DCMOB), were compared to 26 normal weight controls (CTLNW). All underwent cardiac magnetic resonance imaging and 31P spectroscopy to assess function and energetics. Nineteen DCMOB underwent repeat assessment after a dietary weight loss intervention. Adenosine triphosphate (ATP) delivery through creatine kinase (CK flux) was 55% lower in DCMNW than in CTLNW (P = 0.004), correlating with left ventricular ejection fraction (LVEF, r = 0.4, P = 0.015). In contrast, despite similar LVEF (DCMOB 41 ± 7%, DCMNW 38 ± 6%, P = 0.14), CK flux was two-fold higher in DCMOB (P < 0.001), due to higher rate through CK [median kf 0.21 (0.14) vs. 0.11 (0.12) s−1, P = 0.002]. During increased workload, the CTLNW heart increased CK flux by 97% (P < 0.001). In contrast, CK flux was unchanged in DCMNW and fell in DCMOB (by >50%, P < 0.001). Intentional weight loss was associated with positive left ventricular remodelling, with reduced left ventricular end-diastolic volume (by 8%, P < 0.001) and a change in LVEF (40 ± 9% vs. 45 ± 10%, P = 0.002). This occurred alongside a fall in ATP delivery rate with weight loss (by 7%, P = 0.049).

Conclusions

In normal weight, DCM is associated with reduced resting ATP delivery. In obese DCM, ATP demand through CK is greater, suggesting reduced efficiency of energy utilization. Dietary weight loss is associated with significant improvement in myocardial contractility, and a fall in ATP delivery, suggesting improved metabolic efficiency. This highlights distinct energetic pathways in obesity cardiomyopathy, which are both different from dilated cardiomyopathy, and may be reversible with weight loss.
ESC guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 2—care pathways, treatment, and follow-up
Authors:   The Task Force for the management of COVID-19 of the European Society of Cardiology, Baigent Colin , Windecker Stephan , Andreini Daniele , Arbelo Elena , Barbato Emanuele , Bartorelli Antonio L , Baumbach Andreas , Behr Elijah R , Berti Sergio , Bueno Héctor , Capodanno Davide , Cappato Riccardo , Chieffo Alaide , Collet Jean-Philippe , Cuisset Thomas , de Simone Giovanni , Delgado Victoria , Dendale Paul , Dudek Dariusz , Edvardsen Thor , Elvan Arif , González-Juanatey José R , Gori Mauro , Grobbee Diederick , Guzik Tomasz J , Halvorsen Sigrun , Haude Michael , Heidbuchel Hein , Hindricks Gerhard , Ibanez Borja , Karam Nicole , Katus Hugo , Klok Fredrikus A , Konstantinides Stavros V , Landmesser Ulf , Leclercq Christophe , Leonardi Sergio , Lettino Maddalena , Marenzi Giancarlo , Mauri Josepa , Metra Marco , Morici Nuccia , Mueller Christian , Petronio Anna Sonia , Polovina Marija M , Potpara Tatjana , Praz Fabien , Prendergast Bernard , Prescott Eva , Price Susanna , Pruszczyk Piotr , Rodríguez-Leor Oriol , Roffi Marco , Romaguera Rafael , Rosenkranz Stephan , Sarkozy Andrea , Scherrenberg Martijn , Seferovic Petar , Senni Michele , Spera Francesco R , Stefanini Giulio , Thiele Holger , Tomasoni Daniela , Torracca Lucia , Touyz Rhian M , Wilde Arthur A , Williams Bryan
Published: September 2021

Aims

Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular (CV) disease in association with COVID-19.

Methods and results

A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, which was reported previously, focused on the epidemiology, pathophysiology, and diagnosis of CV conditions that may be manifest in patients with COVID-19. This second part addresses the topics of: care pathways and triage systems and management and treatment pathways, both of the most commonly encountered CV conditions and of COVID-19; and information that may be considered useful to help patients with CV disease (CVD) to avoid exposure to COVID-19.

Conclusion

This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.
‘Chez moi pas chez moi’: Home(lessness) in Kim Thúy’s Narratives
Authors: Kistnareddy Ashwiny O
Published: September 2021

In La Nostalgie: Quand donc est-on chez soi? Barbara Cassin posits the home as an ambivalent space where one can feel ‘chez [s]oi’ but also ‘pas chez [s]oi’. Discussing the feeling of being welcomed by those who inhabit the space she calls ‘home’, she underlines homelessness as the lack of hospitality. In a similar vein, Sara Ahmed, examining the notion of feeling ‘at home’, emphasizes the affective and bodily experience that homelessness confers when people are uprooted and need to adapt to a new country and environment. It is from this interrogation of what it means to be at home and homeless, to be homeless and yet at home, that I examine Kim Thúy’s Ru and Mãn, considering the extent to which Thúy’s texts interrogate the notion of forced migration, refugee integration and the ability to rebuild a home in the aftermath of war and displacement.
Longitudinal Associations of Subclinical Hearing Loss With Cognitive Decline
Authors: Irace Alexandria L , Armstrong Nicole M , Deal Jennifer A , Chern Alexander , Ferrucci Luigi , Lin Frank R , Resnick Susan M , Golub Justin S
Published: September 2021

Background

Several studies have demonstrated that age-related hearing loss is associated with cognitive decline. We investigated whether subclinical hearing loss (SCHL) or imperfect hearing traditionally categorized as normal (pure-tone average ≤25 dB) may be similarly linked to cognitive decline and risk of incident mild cognitive impairment (MCI)/dementia.

Methods

Participants from the Baltimore Longitudinal Study of Aging were cognitively normal adults at least 50 years old with cognitive assessments from 1991 to 2019 and pure-tone average ≤25 dB measured between 1991 and 1994 (n = 263). The exposure was hearing based on the better ear pure-tone average. Outcomes were test scores in various cognitive domains. Multivariable linear-mixed effects models were developed to analyze the association between hearing and change in cognition over time, adjusting for age, sex, education, vascular burden, and race. Kaplan–Meier survival curves and Cox proportional hazards models portrayed associations between hearing and incident MCI/dementia diagnosis based on predefined criteria.

Results

Of 263 participants, 145 (55.1%) were female; mean age was 68.3 years (SD = 8.9). Follow-up ranged up to 27.7 years (mean = 11.7 years). Adjusting for multiple comparisons, a 10-dB increase in hearing loss was associated with an annual decline of −0.02 SD (95% confidence interval: −0.03, −0.01) in Letter Fluency. No significant relationships were observed between hearing and incident MCI/dementia.

Conclusions

A relationship between SCHL and cognitive decline was observed for the Letter Fluency test. Further studies are necessary to determine where in the spectrum of hearing loss there begins to be an observable relationship between hearing and cognitive decline.
Development of a psychological empowerment measure for youth in rural Guatemala
Authors: Bakal Michael , Lahiff Maureen , Deardorff Julianna
Published: September 2021

Psychological empowerment (PE) is conceptualized as a context-dependent construct, yet few have studied its applicability to youth in international settings. The current study used a participatory approach to design a measure of empowerment for youth from a rural, Indigenous community in Guatemala and aimed to compare this new measure to extant measures. Youth co-researchers (aged 19–22) collaborated in the development of four culturally relevant empowerment scales through a formative process involving classroom observations and focus groups. Newly developed scales and two widely used, extant scales were administered to a school-based sample of 273 youth (mean age = 14.7, SD = 1.6). Exploratory factor analysis (EFA) showed that one of the newly developed PE scales called Self-Efficacy for Community Action (SECA), which was moderately correlated with the extant scales, appeared to more effectively capture empowerment in the local context than the extant measures. These results support the notion that PE is contextually dependent and suggest that youth participation may aid in instrument design.
Identification of causal metabolites related to multiple autoimmune diseases
Authors: Yu Xing-Hao , Cao Rong-Rong , Yang Yi-Qun , Lei Shu-Feng
Published: September 2021

Observational studies provide evidence that metabolites may be involved in the development of autoimmune diseases (ADs), but whether it is causal is still unknown. Based on the large-scale genome-wide association studies (GWAS) summary statistics, we performed two-sample Mendelian randomization (MR) to evaluate the causal associations between human blood metabolites and multiple ADs, which were inflammatory bowel disease (IBD), ulcerative colitis (UC), crohns disease (CD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), multiple sclerosis (MS), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). After Bonferroni adjustment, we identified 6 causal features of metabolites, i.e., glycerol 2-phosphate for T1D, hexadecanedioate, phenylacetylglutamine and laurylcarnitine for RA, glycine and arachidonate (20:4n6) for CD. Comprehensive sensitive analysis was further performed to validate the robustness of associations. We also observed some overlaps of metabolites among different ADs, implying similar or shared underlying mechanisms in such pathogenic processes. Multivariable MR analysis was then conducted to avoid potential pleiotropic effect of other complex traits. After controlling for several common traits, multivariable MR analysis ruled out most of potential pleiotropic effects and validated independence of identified metabolites. Finally, metabolic pathway analysis was performed based on suggestive metabolites for each AD respectively and a total of seven metabolic pathways were identified. In conclusion, this study provided novel insights into investigating causal role of blood metabolites in development of multiple ADs through a comprehensive genetic pathway.
Fired for Facebook…terminated for Tinder: dismissal for social media misconduct in New Zealand
Authors: Sia Sophie , Cornish René , Tranter Kieran
Published: September 2021

This article reports the findings of a qualitative study of first instance New Zealand employment tribunal decisions concerned with employee dismissal for social media misconduct. There are two main findings. The first relates to the legal approach to employee dismissal for social media misconduct developing in New Zealand. The decisions show New Zealand decision-makers are following the approach in other jurisdictions of treating social media misconduct dismissals as involving a balance between public and private considerations of employment conduct and calculating harm in the employment relationship. However, the decisions do not only track the emerging legal approach to social media misconduct in employment. The decisions are also a record of how social media is affecting employment relations within New Zealand. They are not only legal but also social records. The second finding relates to what the decisions reveal about employment and social media in New Zealand. The sample showed something different from other similar studies. In New Zealand, there was a large cluster of decisions where social media facilitated gender-based harassment. This finding resonates with wider research into New Zealand workplaces that suggests an enduring toxic culture where gender-based harassment is normalized.
Understanding copyright issues entailing deepfakes in India
Authors: Nema Purvi
Published: September 2021

With increase in the scope, scale and sophistication of digitisation, the line between fake and real is blurred. In the recent years, digital disinformation in the form of fake news or morphed pictures/videos has become a new normal on internet. Adding to this list are the artificial intelligence generated-Deepfakes. The wide use of deepfakes in cinematography, fake pornography, political campaigns etc. have fascinated the legal fraternity across the globe. Deepfakes raises many legal alarms including threat to privacy, cyber security, right to publicity, forgery, defamation, criminal intimidation, sedition, copyright infringement, copyright protection, authorship and the list continues. The concern of this article is to understand the copyright issues embroiled in deepfakes in Indian context. The first point of discussion is the sustainability of the claim of copyright infringement or right of publicity arising out of the modification and republication of original work to create deepfakes. Secondly, the creative use of deepfakes like in advanced cinematography would require copyright protection to the author. However, the issue is identifying the author of the deepfake – is it artificial intelligence or the human causing its creation.
Synchronization in epidemic growth and the impossibility of selective containment
Authors: Budich Jan C , Bergholtz Emil J
Published: September 2021

Containment, aiming to prevent the epidemic stage of community-spreading altogether, and mitigation, aiming to merely ‘flatten the curve’ of a wide-ranged outbreak, constitute two qualitatively different approaches to combating an epidemic through non-pharmaceutical interventions. Here, we study a simple model of epidemic dynamics separating the population into two groups, namely a low-risk group and a high-risk group, for which different strategies are pursued. Due to synchronization effects, we find that maintaining a slower epidemic growth behaviour for the high-risk group is unstable against any finite coupling between the two groups. More precisely, the density of infected individuals in the two groups qualitatively evolves very similarly, apart from a small time delay and an overall scaling factor quantifying the coupling between the groups. Hence, selective containment of the epidemic in a targeted (high-risk) group is practically impossible whenever the surrounding society implements a mitigated community-spreading. We relate our general findings to the ongoing COVID-19 pandemic.
Antimicrobial Resistance in Endemic Enteric Infections in Kenya and the Region, and Efforts Toward Addressing the Challenges
Authors: Kariuki Samuel , Wairimu Celestine , Mbae Cecilia
Published: September 2021

Resistance to commonly available antimicrobials is a major threat to the fight against endemic bacterial diseases in sub-Saharan Africa, with a majority of the population unable to afford alternative effective antimicrobial options for management of these diseases. Diseases such as typhoid, cholera, and invasive nontyphoidal Salmonella are among the key enteric infections endemic in most parts of sub-Saharan Africa, especially in displaced populations and among the urban populations living in overcrowded informal settlements. Here, we explore the prevalence and the genomic epidemiology of these infections and the growing problem of multidrug resistance, including emerging resistance to the last line of treatment for these infections. Prevalence rates to commonly available antimicrobials, including ampicillin, chloramphenicol, cotrimoxazole, and tetracycline, now range between 65% and 80%, while 15%–20% of recently studied isolates show reduced susceptibility to fluoroquinolones and emerging resistance to extended-spectrum β-lactams mediated by the CTX-M-15 gene carried on a highly mobile genetic element. The high prevalence of multidrug-resistant isolates including resistance to reserve antibiotics, calls for enhanced control and management options. It will be important for governments in the region to enhance the implementation of national action plans, as guided by the global action plan championed by the World Health Organization, to combat the threat of antimicrobial resistance. However, to yield meaningful results, these efforts will require a strong commitment and enhancement at all levels of healthcare in order. In addition, the use of World Health Organization–approved vaccines in the short to medium term and improvement of water and sanitation in the long term will reduce the burden of disease and antimicrobial resistance in the region.
EQUAL Score Scedosporiosis/Lomentosporiosis 2021: a European Confederation of Medical Mycology (ECMM) tool to quantify guideline adherence
Authors: Stemler Jannik , Lackner Michaela , Chen Sharon C -A , Hoenigl Martin , Cornely Oliver A
Published: September 2021

Background

Invasive scedosporiosis and lomentosporiosis are life-threatening fungal infections in immunocompromised patients with complex diagnostic and treatment patterns.

Objectives

To develop a scoring tool to facilitate and quantify adherence to current guideline recommendations for diagnosis, treatment and follow-up of invasive scedosporiosis and lomentosporiosis.

Methods

Experts from European Confederation of Medical Mycology (ECMM) excellence centres reviewed current guidelines for scedosporiosis and lomentosporiosis. Recommendations for diagnosis, treatment and follow-up were summarized, assembled and weighted according to their strength of recommendation and level of evidence (strongly recommended = 3 points; moderately recommended = 2 points; marginally recommended = 1 point; recommended against = 0 points). Additional items considered of high importance for clinical management were also weighted.

Results

A total of 170 recommendations were identified. A 21-item tool was developed and embedded into the EQUAL score card. Nine items for diagnosis with 18 achievable points were assembled. For treatment, three general recommendation items with a maximal score of 9 were identified, while for specific antifungal treatment the two fungal pathogens were separated. Three and four items were established for scedosporiosis and lomentosporiosis, respectively, with a maximum achievable score of 3 due to the separation of different treatment options with the maximum point value of 3 for voriconazole-based treatment. Follow-up comprised two items (4 points maximum). Key recommendations for clinical outcome were weighted accordingly.

Conclusions

We propose the EQUAL Score Scedosporiosis/Lomentosporiosis to quantify adherence to current guideline recommendations for management of these rare infections. The score remains to be validated in real-life patient cohorts and correlated with patient outcome.
Simulation-Based Investigation of the Performance of Delimiting Trapping Surveys for Insect Pests
Authors: Caton Barney P , Fang Hui , Manoukis Nicholas C , Pallipparambil Godshen R
Published: September 2021

Fully trapped survey designs are widely used to delimit adventive pests populations that can be detected using traps and lures. Delimitation includes verifying the presence of the pest and determining its spatial extent. The size and shape of the survey design and the density of traps can vary; however, resulting variation in detecting efficiency is often unknown. We used a trapping network simulation model with diffusion-based insect movement to investigate delimiting survey trapping design performance for fully trapped and some modified designs. Simulations included randomized outbreak locations in a core area and a duration of 30 d. We assessed impacts of insect dispersal ability, grid size and shape, and trap attractiveness and density on survey performance, measured as mean probability of capturing individual pests [p(capture)]. Most published grids are square, but circles performed equally well and are more efficient. Over different grid sizes, p(capture) increased for insects with greater dispersal ability but was generally unresponsive to size because most captures occurred in central areas. For low dispersing insects, the likelihood of egress was approximately zero with a 3.2-km square grid, whereas an 11.3-km grid was needed to contain highly vagile insects. Trap attractiveness affected p(capture) more strongly than density: lower densities of poorly attractive traps may underperform expectations. Variable density designs demonstrated potential for cost savings but highlighted that resource-intensive outer bands are critical to boundary determination. Results suggesting that many grids are oversized need empirical verification, whereas other principles, such as using circular shapes, are readily adoptable now.
Do Research Joint Ventures Serve a Collusive Function?
Authors: Sovinsky Michelle
Published: September 2021

Every year thousands of firms are engaged in research joint ventures (RJV), where all knowledge gained through research and development (R&D) is shared among members. Most of the empirical literature assumes members are non-cooperative in the product market. But many RJV members are rivals leaving open the possibility that firms may form RJVs to facilitate product market collusion. We examine this by exploiting variation in RJV formation generated by a policy change that affects the collusive benefits but not the research synergies associated with a RJV. We use data on RJVs formed between 1986 and 2001 together with firm-level information from Compustat to estimate a RJV participation equation. After correcting for the endogeneity of R&D and controlling for RJV characteristics and firm attributes, we find the decision to join is impacted by the policy change. We also find the magnitude is significant: the policy change resulted in an average drop in the probability of joining a RJV of $41\%$ among computer and semiconductor manufacturers, $34\%$ among telecommunications firms, and $33\%$ among petroleum refining firms. Our results are consistent with research joint ventures serving a collusive function.
Who Enforces an Arrest Warrant of the International Criminal Court?
Authors: Kawai Keiichiro
Published: September 2021

Though there is an abundance of literature on the relationship between the jurisdiction of the International Criminal Court ('ICC') and the immunities of non-state parties to the ICC Statute, the arrest process under Part 9 of the ICC Statute has not yet been addressed from the perspective of international organizations law. Yet, the ICC is certainly an international organization, and its arrest process is comparable to other organizations’ activities, e.g. the United Nations Security Council’s smart sanctions process. It is therefore argued that a clarification of the legal relationship between the cooperating state and the ICC under the general law of international organization would be a logical premise for further discussion of the relationship between the ICC’s jurisdiction and the immunities of non-state parties to the ICC Statute. The importance of this kind of analysis has become apparent as a consequence of the employment of the Surrogation of Jurisdiction theory by the Appeals Chamber of the ICC in its Al Bashir judgment. This theory formed an essential part of the judgment. An assessment of this theory from the perspective of the law of international organizations shows both the potential and the limitation of the theory. It will, thus, give us a more comprehensive understanding of the theory’s legal implications in the context of the enforcement of ICC arrest warrants against organs of non-state parties to the Statute who enjoy immunity under customary international law.
Directed evolution of Zymomonas mobilis sugar facilitator Glf to overcome glucose inhibition
Authors: Kurgan Gavin , Onyeabor Moses , Holland Steven C , Taylor Eric , Schneider Aidan , Kurgan Logan , Billings Tommy , Wang Xuan
Published: September 2021

Cellular import of D-xylose, the second most abundant sugar in typical lignocellulosic biomass, has been evidenced to be an energy-depriving process in bacterial biocatalysts. The sugar facilitator of Zymomonas mobilis, Glf, is capable of importing xylose at high rates without extra energy input, but is inhibited by D-glucose (the primary biomass sugar), potentially limiting the utility of this transporter for fermentation of sugar mixtures derived from lignocellulose. In this work we developed an Escherichia coli platform strain deficient in glucose and xylose transport to facilitate directed evolution of Glf to overcome glucose inhibition. Using this platform, we isolated nine Glf variants created by both random and site-saturation mutagenesis with increased xylose utilization rates ranging from 4.8-fold to 13-fold relative to wild-type Glf when fermenting 100 g l–1 glucose–xylose mixtures. Diverse point mutations such as A165M and L445I were discovered leading to released glucose inhibition. Most of these mutations likely alter sugar coordinating pocket for the 6-hydroxymethyl group of D-glucose. These discovered glucose-resistant Glf variants can be potentially used as energy-conservative alternatives to the native sugar transport systems of bacterial biocatalysts for fermentation of lignocellulose-derived sugars.