bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex modifies APOE ε4 dose effect on brain tau deposition in cognitively impaired individuals
Authors: Yan Shaozhen , Zheng Chaojie , Paranjpe Manish D , Li Yanxiao , Li Weihua , Wang Xiuying , Benzinger Tammie L S , Lu Jie , Zhou Yun
Published: April 2021

Recent studies in cognitively unimpaired elderly individuals suggest that the APOE ε4 allele exerts a dosage-dependent effect on brain tau deposition. The aim of this study was to investigate sex differences in APOE ε4 gene dosage effects on brain tau deposition in cognitively impaired individuals using quantitative 18F-flortaucipir PET.

Preprocessed 18F-flortaucipir tau PET images, T1-weighted structural MRI, demographic information, global cortical amyloid-β burden measured by 18F-florbetapir PET, CSF total tau and phosphorylated tau measurements were obtained from the Alzheimer’s Disease Neuroimaging Initiative database. Two hundred and sixty-eight cognitively impaired individuals with 146 APOE ε4 non-carriers and 122 carriers (85 heterozygotes and 37 homozygotes) were included in the study. An iterative reblurred Van Cittert iteration partial volume correction method was applied to all downloaded PET images. Magnetic resonance images were used for PET spatial normalization. Twelve regional standardized uptake value ratios relative to the cerebellum were computed in standard space. APOE ε4 dosage × sex interaction effect on 18F-flortaucipir standardized uptake value ratios was assessed using generalized linear models and sex-stratified analysis.

We observed a significant APOE ε4 dosage × sex interaction effect on tau deposition in the lateral temporal, posterior cingulate, medial temporal, inferior temporal, entorhinal cortex, amygdala, parahippocampal gyrus regions after adjusting for age and education level (P < 0.05). The medial temporal, entorhinal cortex, amygdala and parahippocampal gyrus regions retained a significant APOE ε4 dosage × sex interaction effect on tau deposition after adjusting for global cortical amyloid-β (P < 0.05). In sex-stratified analysis, there was no significant difference in tau deposition between female homozygotes and heterozygotes (P > 0.05). In contrast, male homozygotes standardized uptake value ratios were significantly greater than heterozygotes or non-carriers throughout all 12 regions of interest (P < 0.05). Female heterozygotes exhibited significantly increased tau deposition compared to male heterozygotes in the orbitofrontal, posterior cingulate, lateral temporal, inferior temporal, entorhinal cortex, amygdala and parahippocampal gyrus (P < 0.05). Results from voxel-wise analysis were similar to the ones obtained from regions of interest analysis.

Our findings indicate that an APOE ε4 dosage effect on brain region-specific tau deposition exists in males, but not females. These results have important clinical implications towards developing sex and genotype-guided therapeutics in Alzheimer’s disease and uncovers a potential explanation underlying differential APOE ε4-associated Alzheimer’s risk in males and females.
Integrative biochemical, proteomics and metabolomics cerebrospinal fluid biomarkers predict clinical conversion to multiple sclerosis
Authors: Probert Fay , Yeo Tianrong , Zhou Yifan , Sealey Megan , Arora Siddharth , Palace Jacqueline , Claridge Timothy D W , Hillenbrand Rainer , Oechtering Johanna , Leppert David , Kuhle Jens , Anthony Daniel C
Published: April 2021

Eighty-five percent of multiple sclerosis cases begin with a discrete attack termed clinically isolated syndrome, but 37% of clinically isolated syndrome patients do not experience a relapse within 20 years of onset. Thus, the identification of biomarkers able to differentiate between individuals who are most likely to have a second clinical attack from those who remain in the clinically isolated syndrome stage is essential to apply a personalized medicine approach. We sought to identify biomarkers from biochemical, metabolic and proteomic screens that predict clinically defined conversion from clinically isolated syndrome to multiple sclerosis and generate a multi-omics-based algorithm with higher prognostic accuracy than any currently available test. An integrative multi-variate approach was applied to the analysis of cerebrospinal fluid samples taken from 54 individuals at the point of clinically isolated syndrome with 2–10 years of subsequent follow-up enabling stratification into clinical converters and non-converters. Leukocyte counts were significantly elevated at onset in the clinical converters and predict the occurrence of a second attack with 70% accuracy. Myo-inositol levels were significantly increased in clinical converters while glucose levels were decreased, predicting transition to multiple sclerosis with accuracies of 72% and 63%, respectively. Proteomics analysis identified 89 novel gene products related to conversion. The identified biochemical and protein biomarkers were combined to produce an algorithm with predictive accuracy of 83% for the transition to clinically defined multiple sclerosis, outperforming any individual biomarker in isolation including oligoclonal bands. The identified protein biomarkers are consistent with an exaggerated immune response, perturbed energy metabolism and multiple sclerosis pathology in the clinical converter group. The new biomarkers presented provide novel insight into the molecular pathways promoting disease while the multi-omics algorithm provides a means to more accurately predict whether an individual is likely to convert to clinically defined multiple sclerosis.
High resolution structural and functional MRI of the hippocampus in young adults with Down syndrome
Authors: Koenig Katherine A , Oh Se-Hong , Stasko Melissa R , Roth Elizabeth C , Taylor H Gerry , Ruedrich Stephen , Wang Z Irene , Leverenz James B , Costa Alberto C S
Published: April 2021

Down syndrome is the phenotypic consequence of trisomy 21, with clinical presentation including both neurodevelopmental and neurodegenerative components. Although the intellectual disability typically displayed by individuals with Down syndrome is generally global, it also involves disproportionate deficits in hippocampally-mediated cognitive processes. Hippocampal dysfunction may also relate to Alzheimer’s disease-type pathology, which can appear in as early as the first decade of life and becomes universal by age 40. Using 7-tesla MRI of the brain, we present an assessment of the structure and function of the hippocampus in 34 individuals with Down syndrome (mean age 24.5 years ± 6.5) and 27 age- and sex-matched typically developing healthy controls. In addition to increased whole-brain mean cortical thickness and lateral ventricle volumes (P < 1.0 × 10−4), individuals with Down syndrome showed selective volume reductions in bilateral hippocampal subfields cornu Ammonis field 1, dentate gyrus, and tail (P < 0.005). In the group with Down syndrome, bilateral hippocampi showed widespread reductions in the strength of functional connectivity, predominately to frontal regions (P < 0.02). Age was not related to hippocampal volumes or functional connectivity measures in either group, but both groups showed similar relationships of age to whole-brain volume measures (P < 0.05). Finally, we performed an exploratory analysis of a subgroup of individuals with Down syndrome with both imaging and neuropsychological assessments. This analysis indicated that measures of spatial memory were related to mean cortical thickness, total grey matter volume and right hemisphere hippocampal subfield volumes (P < 0.02). This work provides a first demonstration of the usefulness of high-field MRI to detect subtle differences in structure and function of the hippocampus in individuals with Down syndrome, and suggests the potential for development of MRI-derived measures as surrogate markers of drug efficacy in pharmacological studies designed to investigate enhancement of cognitive function.
Effectiveness and Cardiac Safety of Bedaquiline-Based Therapy for Drug-Resistant Tuberculosis: A Prospective Cohort Study
Authors: Brust James C M , Gandhi Neel R , Wasserman Sean , Maartens Gary , Omar Shaheed V , Ismail Nazir A , Campbell Angela , Joseph Lindsay , Hahn Alexandria , Allana Salim , Hernandez-Romieu Alfonso C , Zhang Chenshu , Mlisana Koleka , Viljoen Charle A , Zalta Benjamin , Ebrahim Ismaeel , Franczek Meghan , Master Iqbal , Ramangoaela Limpho , te Riele Julian , Meintjes Graeme
Published: April 2021

Background

Bedaquiline improves treatment outcomes in patients with rifampin-resistant (RR) tuberculosis but prolongs the QT interval and carries a black-box warning from the US Food and Drug Administration. The World Health Organization recommends that all patients with RR tuberculosis receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published.

Methods

We conducted an observational cohort study of patients with RR tuberculosis from 3 provinces in South Africa who received regimens containing bedaquiline. We performed rigorous cardiac monitoring, which included obtaining electrocardiograms in triplicate at 4 time points during bedaquiline therapy. Participants were followed up until the end of therapy or 24 months. Outcomes included final tuberculosis treatment outcome and QT interval prolongation (QT prolongation), defined as any QT interval corrected by the Fridericia method (QTcF) >500 ms or an absolute change from baseline (ΔQTcF) >60 ms.

Results

We enrolled 195 eligible participants, of whom 40% had extensively drug-resistant tuberculosis. Most participants (97%) received concurrent clofazimine. Of the participants, 74% were cured or successfully completed treatment, and outcomes did not differ by human immunodeficiency virus status. QTcF continued to increase throughout bedaquiline therapy, with a mean increase (standard deviation) of 23.7 (22.7) ms from baseline to month 6. Four participants experienced a QTcF >500 ms and 19 experienced a ΔQTcF >60 ms. Older age was independently associated with QT prolongation. QT prolongation was neither more common nor more severe in participants receiving concurrent lopinavir-ritonavir.

Conclusions

Severe QT prolongation was uncommon and did not require permanent discontinuation of either bedaquiline or clofazimine. Close monitoring of the QT interval may be advisable in older patients.
Understanding the uneven geography of urban energy transitions: insights from Edmonton, Canada
Authors: Joshi Neelakshi , Agrawal Sandeep
Published: April 2021

Cities are important partners in developing solutions towards a low-carbon pathway. However, given the variation in geography, a need exists to study urban energy transitions through a nuanced approach that addresses space- and place-based factors. Based on document analysis and interviews with municipal employees and local energy experts in Edmonton, Canada, we explore how location and availability of energy sources, political territoriality, physical urban landscapes and social embeddedness of fossil fuels influence municipal energy transition. Results illustrate that while Edmonton is shaped by its fossil fuel geography, it is actively carving out its low-carbon future through a geographically rooted transition strategy.
Optimization Enabled Black Hole Entropic Fuzzy Clustering Approach for Medical Data
Authors: Rani A Jaya Mabel , Pravin A
Published: April 2021

Medical data clustering is an important part of medical decision systems as it refines highly sensitive information from the huge medical datasets. Medical data clustering includes processes, like determine random clusters, set data into specified clusters and handle data clusters dynamically. Hence, handling of medical data streams and clustering remains a challenging issue. This paper proposes a technique, namely Rider-based sunflower optimization (RSFO) for medical data clustering. Initially, the significant features are selected using the Tversky index with holoentropy that is established from the input data. The holo-entropy is utilized to analyze the relationship between the attributes and features. Here, the clustering is done by a Black Hole Entropic Fuzzy Clustering (BHEFC) algorithm, where the optimal cluster centroids are selected by the proposed RSFO algorithm. The proposed RSFO is designed by incorporating the Rider optimization algorithm (ROA) and sunflower optimization (SFO). The effectiveness of the proposed BHEFC+RSFO algorithm is analyzed by the Dermatology Data Set, and the proposed method has the maximal accuracy of 94.480%, Jaccard coefficient of 94.224% and Rand coefficient of 91.307%, respectively.
IBDDB: a manually curated and text-mining-enhanced database of genes involved in inflammatory bowel disease
Authors: Khan Farhat , Radovanovic Aleksandar , Gojobori Takashi , Kaur Mandeep
Published: April 2021

To date, research on inflammatory bowel disease (IBD, encompassing Crohn’s disease and ulcerative colitis), a chronic complex disorder, has generated a large amount of data scattered across published literature (1 06 333) listed in PubMed on 14 October 2020, and no dedicated database currently exists that catalogues information on genes associated with IBD. We aimed to manually curate 289 genes that are experimentally validated to be linked with IBD and its known phenotypes. Furthermore, we have developed an integrated platform providing information about different aspects of these genes by incorporating several resources and an extensive text-mined knowledgebase. The curated IBD database (IBDDB) allows the selective display of collated 34 subject-specific concepts (listed as columns) exportable through a user-friendly IBDDB portal. The information embedded in concepts was acquired via text-mining of PubMed (manually cleaned and curated), accompanied by data-mining from varied resources. The user can also explore different biomedical entities and their co-occurrence with other entities (about one million) from 11 curated dictionaries in the indexed PubMed records. This functionality permits the user to generate and cross-examine a new hypothesis that is otherwise not easy to comprehend by just reading the published abstracts and papers. Users can download required information using various file formats and can display information in the form of networks. To our knowledge, no curated database of IBD-related genes is available so far. IBDDB is free for academic users and can be accessed at https://www.cbrc.kaust.edu.sa/ibd/.
Tripal MegaSearch: a tool for interactive and customizable query and download of big data
Authors: Jung Sook , Cheng Chun-Huai , Buble Katheryn , Lee Taein , Humann Jodi , Yu Jing , Crabb James , Hough Heidi , Main Dorrie
Published: April 2021

Tripal MegaSearch is a Tripal module for querying and downloading biological data stored in Chado. This module allows site users to select data types, restrict the dataset by applying various filters and then customizing fields to view and download through a single interface. Set by site administrators, example data types include gene, germplasm, marker, map, QTL, genotype, phenotype and expression data. When querying for genes, users can restrict the gene dataset using various filters such as name, chromosome position and functional annotation. They can then customize fields to download, such as name, organism, type, chromosome position, various functional annotations such as BLAST, KEGG, InterPro and GO term. FASTA files can also be downloaded for the sequence data. Site administrators can choose from two different data sources to serve data: Tripal MegaSearch materialized views or Chado tables. If neither data source is desired, administrators may also create their own materialized views and serve them through the flexible dynamic Tripal MegaSearch query form. Tripal MegaSearch is currently implemented in several databases including the Genome Database for Rosaceae www.rosaceae.org and TreeGenes www.https://treegenesdb.org/.
Rank-invariance conditions for the comparison of volatility forecasts
Authors: Palandri Alessandro
Published: April 2021

The paper derives four conditions that guarantee rank-invariance, i.e., that the empirical rankings (based on measurement error-affected variance proxies) of competing volatility forecasts be consistent with the true rankings (based on the unobservable conditional variance). The first three establish bounds beyond which the separation between the forecasts is enough for their rankings not to be affected by the measurement error. The conditions’ ability to establish rank-invariance with respect to forecast characteristics, such as bias, variance and correlation, is studied via Monte Carlo simulations. An additional moment condition identifies the functional forms of the triplet {model, estimation criterion, loss} for which the effects of measurement errors on the rankings cancel altogether. Both theoretical and empirical results show the extension of admissible loss functions achieving ranking consistency in forecast evaluations.
Platypnea and orthodeoxia syndrome as an uncommon clinical indication for a challenging percutaneous patent foramen ovale closure: a case report
Authors: Dipasquale Francesco , Musto Carmine , Pennacchi Mauro , De Felice Francesco
Published: April 2021

Background

Platypnea and Orthodeoxia Syndrome (POS) is a rare clinical condition characterized by positional dyspnoea and arterial desaturation. Various mechanisms are related to this syndrome. The simultaneous presence of abnormal anatomical findings [aortic root dilatation, atrial septal aneurysm (ASA), Lipomatous septum, and patent foramen ovale (PFO)] and an occurring ventilation/perfusion mismatch can modify intracardiac haemodynamics leading to POS in elderly patients.

Case summary

A 70-year-old man was admitted to our emergency department suffering from neurological symptoms. A brain computed tomography scan showed a subdural haematoma and the patient underwent surgical evacuation. Some days later, he experienced an acute pulmonary insufficiency (SpO2 63%) due to parenchymal basal pneumonia treated with endotracheal intubation. Two weeks later, despite pneumonia resolution, the patient’s dyspnoea became worse, experiencing deep hypoxia as soon as the patient sat up with a partial resolution on recumbent position. A transoesophageal echocardiogram with bubble-test was performed showing aortic root dilatation and a lipomatous interatrial septum characterized by the presence of tunnel-like PFO with large ASA resulting in a big right to left shunt at rest with no signs of pulmonary hypertension. The patient underwent PFO percutaneous closure intervention and a few days later O2 therapy was reduced and the patient decannulated.

Discussion

This case illustrates how the presence of both intracardiac and extracardiac factors may facilitate the onset of POS in aged patients. Platypnea and Orthodeoxia Syndrome should be considered in patients with unexplained dyspnoea and arterial desaturation related to orthostatism. It has a good prognosis with an improvement of quality of life if the causal factor can be treated.
Rotatripsy: synergistic effects of complementary technologies: a case report
Authors: Kaur Navjyot , Pruthvi C R , Sharma Yashpaul , Gupta Himanshu
Published: April 2021

Background

Percutaneous coronary intervention (PCI) to calcified coronary lesions (CCLs) remains one of the most complex procedures. Latest modality to modify calcium, intravascular lithotripsy (IVL), has shown good safety and efficacy in preliminary research. However, it may be associated with acute complications, and as standalone therapy, is not sufficient for all CCLs.

Case summary

Eighty-two-year-old man, known case of coronary artery disease and multiple comorbidities, presented with worsening angina of 1 month duration. Coronary angiography revealed heavily calcified triple vessel disease with critical distal left main (LM) involvement. Owing to high surgical risk, he was offered intravascular ultrasound (IVUS) guided PCI with intra-aortic balloon support. While the diffuse, circumferential calcified lesions in LM and left anterior descending (LAD) artery were modified with rotablation (RA) followed by IVL with 3.5 and 3.0 mm balloons; ostial-proximal lesion in left circumflex (LCX) artery was treated with 3.0 mm IVL balloon as a standalone therapy. During second cycle of shockwave therapy in LCX, the 3.0 mm IVL balloon ruptured with type C dissection extending upto LM ostium which required emergent LM bifurcation stenting. We had a good angiographic result which was confirmed with IVUS.

Discussion

ntravascular lithotripsy and RA are complementary technologies in treating CCLs. Rotablation with a relatively small-sized burr is safe and can favourably modify superficial calcium which helps in smooth delivery of IVL balloon and ensures safe shockwave therapy, if required. Unselected upfront use of IVL without intravascular imaging may be associated with complications as described in this case.
Clinical utility of two-phase computed tomography angiography for the detection of myocardial perfusion defects related to acute coronary syndrome in patients with acute chest pain: a case series
Authors: Vallejo Enrique , Buelna-Cano Christian
Published: April 2021

Background

Evaluation of acute chest pain (ACP) in the emergency department is a major health issue and differential diagnosis remains challenging for the physician, particularly in patients with atypical symptoms and inconclusive changes in electrocardiogram (ECG) or biomarkers levels.

Case summary

We present the potential value of the two-phase computed tomography angiography (TP-CTA) imaging protocol done in six different patients evaluated with ACP and underwent non-gated or gated computed tomography angiography (CTA) to exclude pulmonary embolism (PE), acute aortic syndrome (AAS), or acute coronary syndrome (ACS). All patients had new-onset chest pain and atypical clinical presentation with non-diagnostic ECG and initially negative or near-normal cardiac biomarkers.

Discussion

The evaluation of myocardial computed tomography perfusion (MCTP) using TP-CTA imaging protocol might open a new diagnostic approach to evaluate MCTP in patients with ACP related to PE, AAS, or ACS.
Differences Attract: An Experimental Study of Focusing in Economic Choice
Authors: Andersson Ola , Carlson Jim Ingebretsen , Wengström Erik
Published: April 2021

Several behavioural models of choice assume that decision makers place more weight on attributes where options differ more, an assumption we test in a set of experiments. We find that subjects are more likely to choose an option when we add options increasing the maximal difference in the original option’s strongest attribute, suggesting that the decision maker’s focus is drawn to attributes with a high spread. Additional experiments corroborate this finding. Still, we document that the focusing effect diminishes when options are presented using numbers instead of graphs or when subjects are forced to wait before submitting their answers.
The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: the results of the AFFIRM-AHF study
Authors: Jankowska Ewa A , Kirwan Bridget-Anne , Kosiborod Mikhail , Butler Javed , Anker Stefan D , McDonagh Theresa , Dorobantu Maria , Drozdz Jarosław , Filippatos Gerasimos , Keren Andre , Khintibidze Irakli , Kragten Hans , Martinez Felipe A , Metra Marco , Milicic Davor , Nicolau José C , Ohlsson Marcus , Parkhomenko Alexander , Pascual-Figal Domingo A , Ruschitzka Frank , Sim David , Skouri Hadi , van der Meer Peter , Lewis Basil S , Comin-Colet Josep , von Haehling Stephan , Cohen-Solal Alain , Danchin Nicolas , Doehner Wolfram , Dargie Henry J , Motro Michael , Friede Tim , Fabien Vincent , Dorigotti Fabio , Pocock Stuart , Ponikowski Piotr
Published: April 2021

Aims

Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population.

Methods and results

The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5–5.3, P = 0.018) for OSS and 2.8 (0.3–5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3–5.6, P = 0.028) for OSS and 2.9 (0.2–5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM.

Conclusion

In iron-deficient patients with HF and left ventricular ejection fraction <50% who had stabilized after an episode of acute HF, treatment with IV FCM, compared with placebo, results in clinically meaningful beneficial effects on HRQoL as early as 4 weeks after treatment initiation, lasting up to Week 24.
Visualization of intestinal infections with astro- and sapovirus in mink (Neovison vison) kits byin situhybridization
Authors: Birch Julie Melsted , Leijon Mikael , Nielsen Søren Saxmose , Struve Tina , Jensen Henrik Elvang
Published: April 2021

Clarification of the infection microbiology remains a challenge in the pre-weaning diarrhea (PWD) syndrome in farmed mink (Neovison vison). Duodenal, jejunal and colon sections from 36 mink kits with PWD were systematically examined by chromogen in situ hybridization targeting two incriminated viruses: mink astrovirus and mink sapovirus. Using the RNAscope® 2.5 HD Duplex Assay, astrovirus and sapovirus were visualized and simultaneously demonstrated in the gut tissue. Both viruses infect enterocytes in the small intestine with a specific localization pattern; astrovirus affects the two apical thirds of the villi, whereas sapovirus generally affects the basal parts of the villi. Furthermore, we demonstrated that astrovirus in mink does not target the goblet cells. This is the first time astro- and calicivirus have been visualized in mink kit gut tissue, and these findings might be important in clarification of the impact of these viruses in the PWD syndrome.
Public Preferences for Longleaf Pine Restoration Programs in the Southeastern United States
Authors: Oluoch Sydney , Lal Pankaj , Wolde Bernabas , Susaeta Andres , Soto Josè R , Smith Meghann , Adams Damian C
Published: April 2021

Longleaf pine (LLP) (Pinus palustris Mill.) is well known for its role in supporting healthy ecosystems in the southeastern (SE) United States (US). The decline of LLP forest ecosystems has led to a consensus among stakeholders that restoration efforts are needed. However, there is still a lack of robust understanding of the utilization of nonmarket ecosystem services of LLP forests. These challenges have presented major barriers to landowner acceptance of subsidized LLP restoration programs. Understanding the tradeoffs between forest ecosystem services is critical to restoring LLP in the SE US. This study employs the best-worst choice (BWC) method to assess public preferences toward hypothetical LLP restoration programs that consider ecosystem services such as recreation, timber production, carbon sequestration, water yield, and wildlife diversity. We surveyed a representative sample of n = 953 respondents from Alabama, Mississippi, Georgia, and Florida, and results showed that residents in all four states are willing to pay for LLP restoration, with the highest average willingness to pay (WTP) for forest recreation ($20.39), followed by red-cockaded woodpecker (RCW) conservation ($13.37) and carbon sequestration ($13.32). This research provides important public preference information on ecosystem services that is critical in forming sustainable LLP restoration programs.
Gut Microbiota Represent a Major Thermogenic Biomass
Authors: Riedl Ruth A , Burnett Colin M L , Pearson Nicole A , Reho John J , Mokadem Mohamad , Edwards Robert A , Kindel Tammy L , Kirby John R , Grobe Justin L
Published: April 2021

Evidence supports various roles for microbial metabolites in the control of multiple aspects of host energy flux including feeding behaviors, digestive efficiency, and energy expenditure, but few studies have quantified the energy utilization of the biomass of the gut microbiota itself. Because gut microbiota exist in an anoxic environment, energy flux is expected to be anaerobic; unfortunately, commonly utilized O2/CO2 respirometry-based approaches are unable to detect anaerobic energy flux. To quantify the contribution of the gut microbial biomass to whole-animal energy flux, we examined the effect of surgical reduction of gut biomass in C57BL/6J mice via cecectomy and assessed energy expenditure using methods sensitive to anaerobic flux, including bomb and direct calorimetry. First, we determined that cecectomy caused an acceleration of weight gain over several months due to a reduction in combined total host plus microbial energy expenditure, as reflected by an increase in energy efficiency (ie, weight gained per calorie absorbed). Second, we determined that under general anesthesia, cecectomy caused immediate changes in heat dissipation that were significantly modified by short-term pretreatment with dietary or pharmaceutical interventions known to modify the microbiome, and confirmed that these effects were undetectable by respirometry. We conclude that while the cecum only contributes approximately 1% of body mass in the mouse, this organ contributes roughly 8% of total resting energy expenditure, that this contribution is predominantly anaerobic, and that the composition and abundance of the cecal microbial contents can significantly alter its contribution to energy flux.
Meta-GWAS for quantitative trait loci identification in soybean
Authors: Shook Johnathon M , Zhang Jiaoping , Jones Sarah E , Singh Arti , Diers Brian W , Singh Asheesh K
Published: April 2021

We report a meta-Genome Wide Association Study involving 73 published studies in soybean [Glycine max L. (Merr.)] covering 17,556 unique accessions, with improved statistical power for robust detection of loci associated with a broad range of traits. De novo GWAS and meta-analysis were conducted for composition traits including fatty acid and amino acid composition traits, disease resistance traits, and agronomic traits including seed yield, plant height, stem lodging, seed weight, seed mottling, seed quality, flowering timing, and pod shattering. To examine differences in detectability and test statistical power between single- and multi-environment GWAS, comparison of meta-GWAS results to those from the constituent experiments were performed. Using meta-GWAS analysis and the analysis of individual studies, we report 483 peaks at 393 unique loci. Using stringent criteria to detect significant marker-trait associations, 59 candidate genes were identified, including 17 agronomic traits loci, 19 for seed-related traits, and 33 for disease reaction traits. This study identified potentially valuable candidate genes that affect multiple traits. The success in narrowing down the genomic region for some loci through overlapping mapping results of multiple studies is a promising avenue for community-based studies and plant breeding applications.
A head-to-head comparison of ribodepletion and polyA selection approaches for Caenorhabditis elegans low input RNA-sequencing libraries
Authors: Barrett Alec , McWhirter Rebecca , Taylor Seth R , Weinreb Alexis , Miller David M , Hammarlund Marc
Published: April 2021

A recent and powerful technique is to obtain transcriptomes from rare cell populations, such as single neurons in Caenorhabditis elegans, by enriching dissociated cells using fluorescent sorting. However, these cell samples often have low yields of RNA that present challenges in library preparation. This can lead to PCR duplicates, noisy gene expression for lowly expressed genes, and other issues that limit endpoint analysis. Furthermore, some common resources, such as sequence-specific kits for removing ribosomal RNA, are not optimized for nonmammalian samples. To advance library construction for such challenging samples, we compared two approaches for building RNAseq libraries from less than 10 nanograms of C. elegans RNA: SMARTSeq V4 (Takara), a widely used kit for selecting poly-adenylated transcripts; and SoLo Ovation (Tecan Genomics), a newly developed ribodepletion-based approach. For ribodepletion, we used a custom kit of 200 probes designed to match C. elegans rRNA gene sequences. We found that SoLo Ovation, in combination with our custom C. elegans probe set for rRNA depletion, detects an expanded set of noncoding RNAs, shows reduced noise in lowly expressed genes, and more accurately counts expression of long genes. The approach described here should be broadly useful for similar efforts to analyze transcriptomics when RNA is limiting.
A gap in knowledge surrounding urban housing interventions: a call for gender redistribution
Authors: Perri Melissa , O’Campo Patricia
Published: April 2021

Using gender-sensitive (ensures that resource distribution considers gender) and gender-redistributive (aims to develop balanced gendered relationships through redistributing resources) analytic lenses in urban health interventions is long overdue. The social construction of gender and its impact on the health of marginalized women, especially women who experience homelessness within urban settings is frequently overlooked. Housing research, programs, and policies too often fail to utilize gender redistributive frameworks—perpetuating gendered harm for many. This article provides an update of current practices around consideration of gender in housing interventions and literature while advocating for the necessary incorporation of gender-redistributive practices in housing research and program implementation. Addressing these gaps will address the longstanding neglect that has led to disparities among women who experience homelessness or housing insecurity.
India's multi-alignment management and the Russia–India–China (RIC) triangle
Authors: O'Donnell Frank , Papa Mihaela
Published: April 2021

In its Eurasian diplomacy toward Russia and China, India has preferred to engage these states bilaterally and through the Brazil–Russia–India–China–South Africa (BRICS) and Shanghai Cooperation Organization (SCO) multilateral alignments. By contrast, India views the Russia–India–China (RIC) triangle as a less effective mechanism. However, despite its ongoing militarized crisis with China in the spring/summer of 2020, India surprisingly agreed to participate in a meeting of RIC foreign ministers and initiate RIC defence ministers' engagements. India also initiated the revival of RIC summits in 2018. This article analyzes the drivers for India's recent shift toward enhancing RIC. Drawing upon Indian policy statements and alignment documents, the article firstly argues that India generates policy agenda overlaps across RIC, BRICS and SCO, which facilitate forum-shopping. Introducing the case-study of Indian counterterrorism diplomacy across the three alignments, the article secondly argues that Indian dissatisfaction with its progress in advancing a security policy agenda within one grouping leads it to refocus on building this agenda in alternative alignments. This article contributes to conceptualizing multi-alignment management, while providing new insights into Indian relations with Russia and China within multilateral institutions and diplomacy in the era of regime complexity.
Giant left atrial capillary haemangioma invading left-main coronary artery
Authors: Yildirim Serkan , Işik Mehmet , Tanyeli Ömer , Görmüş Niyazi
Published: April 2021

Cardiac haemangiomas are rare cases and can be seen at any age of life. A 49-year-old woman was admitted to our hospital with chest pain. A well-circumscribed soft tissue mass extending from the pulmonary artery truncus to the left ventricular inferior neighborhood. Following surgical resection, the patient was discharged 4 days after surgery.
Confocal endomicroscopy and robot-assisted bronchoplasty integration to treat an endobronchial tumour
Authors: Terra Ricardo Mingarini , Trindade Juliana Mol , Gregório Paulo Henrique Peitl , Pontual Lima Leonardo
Published: April 2021

We present a case of a young man with an endobronchial carcinoid in the left main bronchus, which was treated integrating probe-based confocal laser endomicroscopy and fluorescence imaging during a robot-assisted bronchoplasty. This technique allowed precise detection of the neoplastic area, avoiding associated lung resection. The incorporation of new technologies to our current practice may lead to a better approach to airway tumours.
Superior vena cava replacement for epithelioid haemangioendothelioma
Authors: Svitek Vladimir , Dzian Anton , Mičák Jozef
Published: April 2021

Epitheloid haemangiothelioma is extremely rare malignant tumour of vascular origin. Mediastinal location of this neoplasm with large veins involving is not common. We report a case of epitheloid haemangiothelioma in superior vena cava treated by radical resection and superior vena cava replacement with polytetrafluoroethylene prosthetic graft. There is a certain risk of neurological injury during the cross-clamping of superior vena cava in patient with incompletely obstructed veins. Venovenous shunt is a useful surgical strategy in this type of lesion without necessity of cardiopulmonary bypass use.
Type I Hypersensitivity in Ferrets Following Exposure to SARS-CoV-2 Inoculum: Lessons Learned
Authors: Layton Daniel , Burkett Kathie , Marsh Glenn A , Singanallur Nagendrakumar B , Barr Jennifer , Layton Rachel , Riddell Sarah-Jane , Brown Sheree , Trinidad Lee , Au Gough G , McAuley Alexander J , Lowther Suzanne , Watson James , Vasan Seshadri S
Published: April 2021

This case report discusses Type I hypersensitivity in ferrets following exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inoculum, observed during a study investigating the efficacy of candidate COVID-19 vaccines. Following a comprehensive internal root-cause investigation, it was hypothesized that prior prime-boost immunization of ferrets with a commercial canine C3 vaccine to protect against the canine distemper virus had resulted in primary immune response to fetal bovine serum (FBS) in the C3 preparation. Upon intranasal exposure to SARS-CoV-2 virus cultured in medium containing FBS, an allergic airway response occurred in 6 out of 56 of the ferrets. The 6 impacted ferrets were randomly dispersed across study groups, including different COVID-19 vaccine candidates, routes of vaccine candidate administration, and controls (placebo). The root-cause investigation and subsequent analysis determined that the allergic reaction was unrelated to the COVID-19 vaccine candidates under evaluation. Histological assessment suggested that the allergic response was characterized by eosinophilic airway disease; increased serum immunoglobulin levels reactive to FBS further suggested this response was caused by immune priming to FBS present in the C3 vaccine. This was further supported by in vivo studies demonstrating ferrets administered diluted FBS also presented clinical signs consistent with a hyperallergic response, while clinical signs were absent in ferrets that received a serum-free SARS-CoV-2 inoculum. It is therefore recommended that vaccine studies in higher order animals should consider the impact of welfare vaccination and use serum-free inoculum whenever possible.
Solving block low-rank linear systems by LU factorization is numerically stable
Authors: Higham Nicholas J , Mary Theo
Published: April 2021

Block low-rank (BLR) matrices possess a blockwise low-rank property that can be exploited to reduce the complexity of numerical linear algebra algorithms. The impact of these low-rank approximations on the numerical stability of the algorithms in floating-point arithmetic has not previously been analysed. We present rounding error analysis for the solution of a linear system by LU factorization of BLR matrices. Assuming that a stable pivoting scheme is used, we prove backward stability: the relative backward error is bounded by a modest constant times $\varepsilon $, where the low-rank threshold $\varepsilon $ is the parameter controlling the accuracy of the blockwise low-rank approximations. In addition to this key result, our analysis offers three new insights into the numerical behaviour of BLR algorithms. First, we compare the use of a global or local low-rank threshold and find that a global one should be preferred. Second, we show that performing intermediate recompressions during the factorization can significantly reduce its cost without compromising numerical stability. Third, we consider different BLR factorization variants and determine the update–compress–factor variant to be the best. Tests on a wide range of matrices from various real-life applications show that the predictions from the analysis are realized in practice.
Analyzing the Weyl Construction for Dynamical Cartan Subalgebras
Authors: Duwenig Anna , Gillaspy Elizabeth , Norton Rachael
Published: April 2021

When the reduced twisted $C^*$-algebra $C^*_r({\mathcal{G}}, c)$ of a non-principal groupoid ${\mathcal{G}}$ admits a Cartan subalgebra, Renault’s work on Cartan subalgebras implies the existence of another groupoid description of $C^*_r({\mathcal{G}}, c)$. In an earlier paper, joint with Reznikoff and Wright, we identified situations where such a Cartan subalgebra arises from a subgroupoid ${\mathcal{S}}$ of ${\mathcal{G}}$. In this paper, we study the relationship between the original groupoids ${\mathcal{S}}, {\mathcal{G}}$ and the Weyl groupoid and twist associated to the Cartan pair. We first identify the spectrum ${\mathfrak{B}}$ of the Cartan subalgebra $C^*_r({\mathcal{S}}, c)$. We then show that the quotient groupoid ${\mathcal{G}}/{\mathcal{S}}$ acts on ${\mathfrak{B}}$, and that the corresponding action groupoid is exactly the Weyl groupoid of the Cartan pair. Lastly, we show that if the quotient map ${\mathcal{G}}\to{\mathcal{G}}/{\mathcal{S}}$ admits a continuous section, then the Weyl twist is also given by an explicit continuous $2$-cocycle on ${\mathcal{G}}/{\mathcal{S}} \ltimes{\mathfrak{B}}$.
On the Classification of Normal Stein Spaces and Finite Ball Quotients With Bergman–Einstein Metrics
Authors: Ebenfelt Peter , Xiao Ming , Xu Hang
Published: April 2021

We study the Bergman metric of a finite ball quotient $\mathbb{B}^n/\Gamma $, where $n \geq 2$ and $\Gamma \subseteq{\operatorname{Aut}}({\mathbb{B}}^n)$ is a finite, fixed point free, abelian group. We prove that this metric is Kähler–Einstein if and only if $\Gamma $ is trivial, that is, when the ball quotient $\mathbb{B}^n/\Gamma $ is the unit ball ${\mathbb{B}}^n$ itself. As a consequence, we characterize the unit ball among normal Stein spaces with isolated singularities and abelian fundamental groups in terms of the existence of a Bergman–Einstein metric.
Empty Axis-Parallel Boxes
Authors: Bukh Boris , Chao Ting-Wei
Published: April 2021

We show that, for every set of $n$ points in the $d$-dimensional unit cube, there is an empty axis-parallel box of volume at least $\Omega (d/n)$ as $n\to \infty $ and $d$ is fixed. In the opposite direction, we give a construction without an empty axis-parallel box of volume $O(d^2\log d/n)$. These improve on the previous best bounds of $\Omega (\log d/n)$ and $O(2^{7d}/n)$, respectively.
Masked and distanced: a qualitative study of how personal protective equipment and distancing affect teamwork in emergency care
Authors: Hayirli Tuna C , Stark Nicholas , Bhanja Aditi , Hardy James , Peabody Christopher R , Kerrissey Michaela J
Published: April 2021

Background

Newly intensified use of personal protective equipment (PPE) in emergency departments presents teamwork challenges affecting the quality and safety of care at the frontlines.

Objective

We conducted a qualitative study to categorize and describe barriers to teamwork posed by PPE and distancing in the emergency setting.

Methods

We conducted 55 semi-structured interviews between June 2020 and August 2020 with personnel from two emergency departments serving in a variety of roles. We then performed a thematic analysis to identify and construct patterns of teamwork challenges into themes.

Results

We discovered two types of challenges to teamwork: material barriers related to wearing masks, gowns and powered air-purifying respirators, and spatial barriers implemented to conserve PPE and limit coronavirus exposure. Both material and spatial barriers resulted in disrupted communication, roles and interpersonal relationships, but they did so in unique ways. Material barriers muffled information flow, impeded team member recognition and role/task division, and reduced belonging and cohesion while increasing interpersonal strain. Spatial barriers resulted in mediated communication and added physical and emotional distance between teammates and patients.

Conclusion

Our findings identify specific aspects of how intensified PPE use disrupts teamwork and can inform efforts to ensure care quality and safety in emergency settings as PPE use continues during and, potentially beyond, the coronavirus disease-2019 pandemic.