bluuebunny/crossref_metadata_2025 huggingface dataset:
Moderately Discontinuous Homotopy
Authors: Fernández de Bobadilla Javier , Heinze Sonja , Pe Pereira Maria
Published: August 2021

We introduce a metric homotopy theory, which we call moderately discontinuous homotopy, designed to capture Lipschitz properties of metric singular subanalytic germs. It matches with the moderately discontinuous homology theory recently developed by the authors and E. Sampaio. The $k$-th MD homotopy group is a group $MDH^b_{\bullet }$ for any $b\in [1,\infty ]$ together with homomorphisms $MD\pi ^b\to MD\pi ^{b^{\prime}}$ for any $b\geq b^{\prime}$. We develop all its basic properties including finite presentation of the groups, long homotopy sequences of pairs, metric homotopy invariance, Seifert van Kampen Theorem, and the Hurewicz Isomorphism Theorem. We prove comparison theorems that allow to relate the metric homotopy groups with topological homotopy groups of associated spaces. For $b=1$, it recovers the homotopy groups of the tangent cone for the outer metric and of the Gromov tangent cone for the inner one. In general, for $b=\infty $, the $MD$-homotopy recovers the homotopy of the punctured germ. Hence, our invariant can be seen as an algebraic invariant interpolating the homotopy from the germ to its tangent cone. We end the paper with a full computation of our invariant for any normal surface singularity for the inner metric. We also provide a full computation of the MD-homology in the same case.
ProjectFlow: a configurable workflow management application for point of care research
Authors: Dhond Rupali , Elbers Danne , Majahalme Nilla , Dipietro Svitlana , Goryachev Sergey , Acher Ryan , Leatherman Sarah , Anglin-Foote Tori , Liu Qingzhu , Su Shaoyu , Seerapu Ramana , Hall Robert , Ferguson Ryan , Brophy Mary T , Ferraro Jeff , DuVall Scott L , Do Nhan V
Published: September 2021

Objective

To best meet our point-of-care research (POC-R) needs, we developed ProjectFlow, a configurable, clinical research workflow management application. In this article, we describe ProjectFlow and how it is used to manage study processes for the Diuretic Comparison Project (DCP) and the Research Precision Oncology Program (RePOP).

Materials and methods

The Veterans Health Administration (VHA) is the largest integrated health care system in the United States. ProjectFlow is a flexible web-based workflow management tool specifically created to facilitate conduct of our clinical research initiatives within the VHA. The application was developed using the Grails web framework and allows researchers to create custom workflows using Business Process Model and Notation.

Results

As of January 2021, ProjectFlow has facilitated management of study recruitment, enrollment, randomization, and drug orders for over 10 000 patients for the DCP clinical trial. It has also helped us evaluate over 3800 patients for recruitment and enroll over 370 of them into RePOP for use in data sharing partnerships and predictive analytics aimed at optimizing cancer treatment in the VHA.

Discussion

The POC-R study design embeds research processes within day-to-day clinical care and leverages longitudinal electronic health record (EHR) data for study recruitment, monitoring, and outcome reporting. Software that allows flexibility in study workflow creation and integrates with enterprise EHR systems is critical to the success of POC-R.

Conclusions

We developed a flexible web-based informatics solution called ProjectFlow that supports custom research workflow configuration and has ability to integrate data from existing VHA EHR systems.
Allocation strategies of carbon, nitrogen and phosphorus following a gradient of wildfire severities
Authors: Song Zhaopeng , Li Zhaolei , Luo Yiqi , Liu Yanhong
Published: August 2021

Wildfire is crucial in the regulation of nutrient allocation during the succession of boreal forests. However, the allocation strategies of carbon (C), nitrogen (N) and phosphorus (P) between leaves and fine roots in response to wildfire severities remain poorly studied. We aimed to explore the allocation strategies of C, N and P between leaves and fine roots among different fire severities. We selected four wildfire severities (unburned, low, moderate and high severity) after 10 years recovery in the Great Xing’an Mountains, northeast China, and compared C, N and P concentrations in leaves and fine roots of all species among fire severities using stoichiometry theory and allometric growth equations. Compared with unburned treatment, C concentrations in leaves and fine roots increased at low severity, and leaf N concentration was the greatest at high severity, but the lowest fine root N concentration occurred at high severity. Plant nutrient utilization tended to be P-limited at high fire severity according to the mean value of N:P ratio > 16. More importantly, C, N and P allocation strategies between fine roots and leaves changed from allometry to isometry with increasing fire severities, which showed more elements allocated to leaves than to fine roots with increasing fire severities. These changes in patterns suggest that the allocation strategies of elements between leaves and fine roots are of imbalance with the wildfire severity. This study deepens our understanding of nutrient dynamics between plant and soil in ecosystem succession.
Giant abdominopelvic desmoid tumour herniated trough perineum: a case report
Authors: Tchangai Boyodi Katanga , Tchaou Mazamaesso , Alassani Fousseni , Amétitovi Joel Ekoué , Doh Kwamé , Darre Tchin , Dosseh David Ekoue
Published: August 2021

Desmoid tumours are deep aggressive fibromatoses that usually arise in the soft tissues of the limbs or the abdominal wall. Intra-abdominal localisation, rarely occurs and their treatment may be challenging. When necessary, surgery must be personalized to what is achievable in terms of margins while preserving functional outcomes. This condition is illustrated herein with the case of a 40-year-old female presenting an unusually large sporadic desmoid tumour with abdominal, pelvic and perineal involvement. Resection was performed without organ involvement through a combined perineal approach. Tumour resection was macroscopically completed except in the perineum, where the tumour was left (R2 resection) to preserve anal sphincter. Adjuvant treatment with tamoxifen was given to achieve local control. The hormonal treatment was well tolerated, and no recurrence was observed after 36 months of follow-up.
Playing Cute: Sensation Villainy and the Aesthetics of Small Things in The Woman in White and Lady Audley’s Secret
Authors: Eastlake Laura
Published: September 2021

In Our Aesthetic Categories (2012), Sianne Ngai defines ‘cute’ as an aesthetic ‘preoccupation with small, easy to handle things . . . an aesthetic that celebrates the diminutive and the vulnerable’. Although Ngai identifies the cute as a predominantly twentieth-century phenomenon, and one which is inextricably bound up with the mass-market commodification, even eroticization and fetishization of the cute object or person, it is difficult to imagine a literary character more enamoured with ‘small things’ – from tiny, sugary confections to his menagerie of pet mice – than Wilkie Collins’s Count Fosco, or a character who so perfectly conforms to the definition of the cute commodity itself as ‘appealing specifically . . . for protection and care’ than the ‘childish, helpless, babyfied’ Lucy Audley in Mary Elizabeth Braddon’s Lady Audley’s Secret (1862). This article reads Count Fosco and Lady Audley through the characteristics of cuteness to better understand the aesthetic and economic dynamics of their villainy, and to establish for the twentieth-century phenomenon of cuteness identified by Ngai a discernible genealogy in the specific conjunction of print culture, theatricality, commodification, and physical sensation that we now recognize as the sensation fiction of the 1860s.
Rapid recovery by fat- and muscle-depleted Blackpoll Warblers following trans-oceanic migration is driven by time-minimization
Authors: Bayly Nicholas J , Rosenberg Kenneth V , Norris D Ryan , Taylor Philip D , Hobson Keith A
Published: September 2021

Nonstop endurance flights are a defining characteristic of many long-distance migratory birds, but subsequent recovery phases are not typically distinguished from fueling phases (collectively “stopovers”), despite endurance flights inducing marked physiological changes including flight muscle atrophy and gastrointestinal tract reductions. Here, we hypothesize that recovery requires unique behavioral adaptations, leading to departures from the predictions of optimal migration theory for time-minimizing migrants. We predict that recovering birds will (1) select (moist) food-rich habitats on arrival; (2) have slow initial fueling rates due to decreased gastrointestinal capacity; (3) show a negative correlation between stopover duration and arrival condition instead of a negative correlation with fuel deposition rate (FDR); (4) stopover longer than required to store energy reserves for subsequent flights; and (5) show evidence of rebuilding flight muscles. To test these predictions, we studied Blackpoll Warblers (Setophaga striata) in northern Colombia following trans-oceanic flights >2,250 km. Birds selected dry seasonal habitats, despite the proximity of moist forests, and among 1,227 captured individuals, 14–21% were emaciated and 88% had atrophied flight muscles. We recaptured 74 individuals, revealing net positive mass gains and, contrary to prediction (2), no evidence for slow initial recovery rates. Contrary to prediction (3), stopover duration was only weakly correlated with arrival condition and birds with high FDR (4.9% lean body mass day–1) had shorter durations (3 days) relative to birds with slower rates (7 days): both groups accumulated sufficient fuel to reach nonbreeding (over-wintering) grounds 500–1,000 km away. Mass increases were largely attributable to fat deposition but some birds improved flight muscle condition (31.9%), consistent with prediction (5). Together these results reveal a strong selection for time-minimization in the decisions made by Blackpoll Warblers following trans-oceanic flights, likely mediated through advantages to early arrival on nonbreeding grounds, contrary to our hypothesis of recovery imposing unique selection pressures.
Evaluation of inducible promoter–riboswitch constructs for heterologous protein expression in the cyanobacterial species Anabaena sp. PCC 7120
Authors: Svoboda Jessee , Cisneros Brenda , Philmus Benjamin
Published: September 2021

Cyanobacteria are promising chassis for synthetic biology applications due to the fact that they are photosynthetic organisms capable of growing in simple, inexpensive media. Given their slower growth rate than other model organisms such as Escherichia coli and Saccharomyces cerevisiae, there are fewer synthetic biology tools and promoters available for use in model cyanobacteria. Here, we compared a small library of promoter–riboswitch constructs for synthetic biology applications in Anabaena sp. PCC 7120, a model filamentous cyanobacterium. These constructs were designed from six cyanobacterial promoters of various strengths, each paired with one of two theophylline-responsive riboswitches. The promoter–riboswitch pairs were cloned upstream of a chloramphenicol acetyltransferase (cat) gene, and CAT activity was quantified using an in vitro assay. Addition of theophylline to cultures increased the CAT activity in almost all cases, allowing inducible protein production with natively constitutive promoters. We found that riboswitch F tended to have a lower induced and uninduced production compared to riboswitch E for the weak and medium promoters, although the difference was larger for the uninduced production, in accord with previous research. The strong promoters yielded a higher baseline CAT activity than medium strength and weak promoters. In addition, we observed no appreciable difference between CAT activity measured from strong promoters cultured in uninduced and induced conditions. The results of this study add to the genetic toolbox for cyanobacteria and allow future natural product and synthetic biology researchers to choose a construct that fits their needs.
Prevalence of Breast Cancer in Female Physicians Performing Procedures With Significant Fluoroscopy Exposure: Survey
Authors: Biglione Bianca , Nakhaei Masoud , Hamilton Barbara , Englander Meridith J. , Dua Anahita , Brook Olga R.
Published: September 2021

Objective

The aim of this study was to assess self-reported breast cancer prevalence potentially associated with occupational radiation exposure from fluoroscopy-guided procedures in female physicians using current standard protection measures.

Methods

An institutional review board–approved survey was shared as a link to self-identified female physicians. We compared self-reported prevalence of breast cancer among women physicians with longer than 10 years of postfellowship practice in specialties with heavy fluoroscopy exposure versus specialties with low fluoroscopy exposure. We compared the distribution of breast cancer risk factors and personal radiation safety measures.

Results

A total of 303 women physicians participated in the survey. There were 8 (16%) of 49 from the first study group and 8 (18%) of 44 from the second study group who self-reported a diagnosis of breast cancer. There were no differences in the distribution of breast cancer risk factors between the 2 groups or prevalence of breast cancer (P = 0.81).

Conclusions

Self-reported breast cancer prevalence is similar between women physicians who are practicing fluoroscopically heavy and light medical specialties.
A Metric for Quantification of Iodine Contrast Enhancement (Q-ICE) in Computed Tomography
Authors: Szczykutowicz Timothy P. , Viggiano Ben , Rose Sean , Pickhardt Perry J. , Lubner Meghan G.
Published: September 2021

Background

Poor contrast enhancement is related to issues with examination execution, contrast prescription, computed tomography (CT) protocols, and patient conditions. Currently, our community has no metric to monitor true enhancement on routine single-phase examinations because this requires knowledge of both pre- and postcontrast CT number.

Purpose

We propose an automatable solution to quantifying contrast enhancement without requiring a dedicated noncontrast series.

Methods

The difference in CT number between a target region in an enhanced and unenhanced image defines the metric “quantification of iodine contrast enhancement” (Q-ICE). Quantification of iodine contrast enhancement uses the noncontrast bolus tracking baseline image from routine abdominal examinations, which mitigates the need for a dedicated noncontrast series. We applied this method retrospectively to 312 patient livers from 2 sites between 2017 and 2020. Each site used a weight-based contrast injection protocol for weights 60 to 113 kg and a constant volume less than 60 kg and greater than 113 kg. Hypothesis testing was performed to compare Q-ICE between sites and detect Q-ICE dependence on weight and kilovoltage (kV).

Results

Mean Q-ICE differed between sites (P = 0.004) by 4.96 Hounsfield unit with 95% confidence interval (1.63–8.28), albeit this difference was roughly 2 times smaller than the SD in Q-ICE across patients at a single site. For patients between 60 and 113 kg, we did not observe evidence of Q-ICE varying with patient weight (P = 0.920 and 0.064 for 120 and 140 kV, respectively). The Q-ICE did vary with patient weight for patients less than 60 kg (P = 0.003) and greater than 113 kg (P = 0.04). We observed a roughly 10 Hounsfield unit reduction in Q-ICE liver for patients scanned with 140 versus 120 kV. We observed several underenhancing examinations with an arterial phase appearance motivating our CT protocol optimization team to consider increasing the delay for slowly enhancing patients.

Conclusions

A quality metric for quantifying CT contrast enhancement was developed and suggested tangible opportunities for quality improvement and potential financial savings.
Monosodium Urate Crystal Deposition in Coronary Artery Plaque by 128-Slice Dual-Energy Computed Tomography: An Ex Vivo Phantom and In Vivo Study
Authors: Feuchtner Gudrun M. , Plank Fabian , Beyer Christoph , Schwabl Christoph , Held Julia , Bellmann-Weiler Rosa , Weiss Guenther , Gruber Johann , Widmann Gerlig , Klauser Andrea S.
Published: September 2021

Objective

Monosodium uric acid (MSU) crystals may accumulate in the coronary plaque. The objective was to assess whether dual-energy computed tomography (DECT) allows for detection of MSU in coronary plaque.

Methods

Patients were examined with 128-slice DECT applying a cardiac electrocardiogram-gated and peripheral extremity protocol. Patients were divided into 3 groups: gout (tophi >1 cm in peripheral joints), hyperuricemia (>6.5 mg/dL serum uric acid), and controls. The groups were matched for cardiovascular risk factors. Monosodium uric acid–positive (+) and calcified plaque were distinguished, and the coronary artery calcium score was calculated. Ex vivo phantom: MSU solutions were diluted in different NaCL solutions (5%/10%/15%/20%/25%). Coronary artery models with 2 different plaque types (MSU+ and calcified) were created.

Results

A total of 96 patients were included (37 with gout, 33 with hyperuricemia, and 26 controls). Monosodium uric acid–positive plaques were found more often in patients with gout as compared with controls (91.9% vs 0.38%; P < 0.0001), and the number of plaques was higher (P < 0.0001). Of 102 MSU+ plaques, 26.7% were only MSU+ and 74.2% were mixed MSU+/calcified. Monosodium uric acid–positive plaque had mean 232.3 Hounsfield units (range, 213–264). Coronary artery calcium score was higher in patients with gout as compared with controls (659.1 vs 112.4 Agatston score; P < 0.001). Patients with gout had more MSU+ plaques as compared with patients with hyperuricemia (91.6% vs 2.9%; P < 0.0001), and coronary artery calcium score was higher (659.1 vs 254 Agatston score; P < 0.001), but there was no difference between patients with hyperuricemia and controls. Ex vivo phantom study: MSU crystals were detected by DECT in solutions with a concentration of 15% or greater MSU and could be distinguished from calcified.

Conclusions

Coronary MSU+ plaques can be detected by DECT in patients with gout.
Genetic and Demographic Predictors of Latent Reading Ability in Two Cohorts
Authors: Lancaster Hope Sparks , Dinu Valentin , Li Jing , Gruen Jeffrey R ,   The GRaD Consortium
Published: August 2021

Reading ability is a complex skill requiring multiple proficiencies (e.g., phonological awareness, decoding, and comprehension). Reading ability has genetic and environmental components that create the potential for significant gene-gene and gene-environment interactions, but the evidence for these interactions is limited. We used data from the Avon Longitudinal Study of Parents and Children and the Genes, Reading and Dyslexia Study to assess the contributions of genetic and demographic features to a continuous latent reading ability score. We then used this score as the phenotype on which to predicate genome-wide single nucleotide polymorph screening, followed by feature selection using an elastic net analysis. Results from the elastic net models showed that genetic and demographic features predicted reading ability for both cohorts. Five single nucleotide polymorphisms were associated with latent reading in the Avon Longitudinal Study of Parents and Children, as well as in the Genes, Reading and Dyslexia cohorts. For both cohorts, larger vocabularies were positively associated with latent reading ability. Genes within the neuron migration pathway were overrepresented in the Avon Longitudinal Study of Parents and Children cohort. We provide support that genes involved in early brain development have an impact on latent reading ability performance. Our findings also indicate high generalizability of genetic findings between cohorts, using our approach.
Prolonged SARS-CoV-2 infection in patients with lymphoid malignancies
Authors: Lee Christina Y. , Shah Monika K. , Hoyos David , Solovyov Alexander , Douglas Melanie , Taur Ying , Maslak Peter G. , Babady N. Esther , Greenbaum Benjamin , Kamboj Mini , Vardhana Santosha A.
Published: August 2021

Coronavirus disease 2019 (COVID-19) infection results in high mortality rates in patients with hematologic malignancies. Persistent and/or recurrent COVID-19 has not yet been demonstrated in this population. We identified patients with B-cell lymphomas as having a particularly high risk for persistent SARS-CoV-2 positivity. Subsequent analysis of patients with lymphoid malignancies and COVID-19 identified discrete risk factors for severity of primary infection as compared to disease chronicity. Active therapy and diminished T-cell counts were key drivers of acute mortality in lymphoma patients with COVID-19 infection. Conversely, B-cell depleting therapy was the primary driver of re-hospitalization for COVID-19. In patients with persistent SARS-CoV-2 positivity, we observed high levels of viral entropy consistent with intrahost viral evolution, particularly in patients with impaired CD8+ T-cell immunity. These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population.

Statement of Significance

We establish persistent symptomatic COVID-19 infection as a novel clinical syndrome in patients with lymphoid malignancies and identify B-cell depletion as the key immunologic driver of persistent infection. Furthermore, we demonstrate ongoing intrahost viral evolution in patients with persistent COVID-19 infection, particularly in patients with impaired CD8+ T-cell immunity.
Differential expression of genes influencing mitotic processes in cord blood mononuclear cells after a pre-conceptional micronutrient-based randomized controlled trial: Pune Rural Intervention in Young Adolescents (PRIYA)
Authors: Khare Satyajeet P. , Madhok Ayush , Patta Indumathi , Sukla Krishna K. , Wagh Vipul V. , Kunte Pooja S. , Raut Deepa , Bhat Dattatray , Kumaran Kalyanaraman , Fall Caroline , Tatu Utpal , Chandak Giriraj R. , Yajnik Chittaranjan S. , Galande Sanjeev
Published: August 2021

In The Pune Maternal Nutrition Study, vitamin B12 deficiency was seen in 65% of pregnant women, folate deficiency was rare. Maternal total homocysteine concentrations were inversely associated with offspring birthweight, and low vitamin B12 and high folate concentrations predicted higher offspring adiposity and insulin resistance. These findings guided a nested pre-conceptional randomized controlled trial ‘Pune Rural Intervention in Young Adolescents (PRIYA)’. The interventions included: 1) vitamin B12+multi-micronutrients the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) and proteins (B12+MMN), 2) vitamin B12 (B12 alone), and 3) placebo. Intervention improved maternal pre-conceptional and in-pregnancy micronutrient nutrition. Gene expression analysis in cord blood mononuclear cells in 88 pregnancies revealed 75 differentially expressed genes between the B12+MMN and placebo groups. The enriched biological processes included G2/M phase transition, chromosome segregation, and nuclear division. Enriched pathways included, mitotic spindle checkpoint and DNA damage response while enriched human phenotypes were sloping forehead and decreased head circumference. Fructose-bisphosphatase 2 (FBP2) and Cell Division Cycle Associated 2 (CDCA2) genes were under-expressed in the B12 alone group. The latter, involved in chromosome segregation was under-expressed in both intervention groups. Based on the role of B-complex vitamins in the synthesis of nucleotides and S-Adenosyl Methionine, and the roles of vitamins A and D on gene expression, we propose that the multi-micronutrient intervention epigenetically affected cell cycle dynamics. Neonates in the B12+MMN group had the highest ponderal index. Follow up studies will reveal if the intervention and the altered biological processes influence offspring diabesity.
Thalamic deep brain stimulation modulates circadian and infradian cycles of seizure risk in epilepsy
Authors: Gregg Nicholas M. , Sladky Vladimir , Nejedly Petr , Mivalt Filip , Kim Inyong , Balzekas Irena , Sturges Beverly K. , Crowe Chelsea , Patterson Edward E. , Van Gompel Jamie J. , Lundstrom Brian N. , Leyde Kent , Denison Timothy J. , Brinkmann Benjamin H. , Kremen Vaclav , Worrell Gregory A.
Published: August 2021

Chronic brain recordings suggest that seizure risk is not uniform, but rather varies systematically relative to daily (circadian) and multiday (infradian) cycles. Here, one human and seven dogs with naturally occurring epilepsy had continuous intracranial EEG (median 298 days) using novel implantable sensing and stimulation devices. Two pet dogs and the human subject received concurrent thalamic deep brain stimulation (DBS) over multiple months. All subjects had circadian and infradian cycles in the rate of interictal epileptiform spikes (IES). There was seizure phase locking to circadian and infradian IES cycles in five and seven out of eight subjects, respectively. Thalamic DBS modified circadian (all 3 subjects) and infradian (analysis limited to the human participant) IES cycles. DBS modified seizure clustering and circadian phase locking in the human subject. Multiscale cycles in brain excitability and seizure risk are features of human and canine epilepsy and are modifiable by thalamic DBS.
Associations between residential exposure to volatile organic compounds (VOCs) and liver injury markers
Authors: Wahlang Banrida , Gripshover Tyler C. , Gao Hong , Krivokhizhina Tatiana , Keith Rachel J. , Sithu Israel D. , Rai Shesh N. , Bhatnagar Aruni , McClain Craig J. , Srivastava Sanjay , Cave Mathew C.
Published: August 2021

Occupational exposures to volatile organic compounds (VOCs) have been associated with numerous health complications including steatohepatitis and liver cancer. However, the potential impact of environmental/residential VOC exposures on liver health and function is largely unknown. To address this knowledge gap, the objective of this cross-sectional study is to investigate associations between VOCs and liver injury biomarkers in community residents. Subjects were recruited from six Louisville neighborhoods, and informed consent was obtained. Exposure biomarkers included 16 creatinine-adjusted urinary metabolites corresponding to 12 parent VOCs. Serological disease biomarkers measured included cytokertain-18 (K18 M65 and M30), liver enzymes and direct bilirubin. Associations between exposure and disease biomarkers were assessed using generalized linear models. Smoking status was confirmed through urinary cotinine levels. The population comprised of approximately 60% females and 40% males; White persons accounted 78% of the population; with more nonsmokers (n=413) than smokers (n=250). When compared to nonsmokers, Males (45%) and Black persons (26%) were more likely to be smokers. In the overall population, metabolites of acrolein, acrylonitrile, acrylamide, 1,3-butadiene, crotonaldehyde, styrene and xylene were positively associated with alkaline phosphatase (ALP). These associations persisted in smokers, with the exception of crotonaldehyde, and addition of N,N dimethylformamide and propylene oxide metabolites. Although no positive associations were observed for K18 M30, the benzene metabolite was positively associated with bilirubin, irrespective of smoking status. Taken together, the results demonstrated that selected VOCs were positively associated with liver injury biomarkers. These findings will enable better risk assessment and identification of populations vulnerable to liver disease.
Predicting brain amyloid-β PET phenotypes with graph convolutional networks based on functional MRI and multi-level functional connectivity
Authors: Li Chaolin , Liu Mianxin , Xia Jing , Mei Lang , Yang Qing , Shi Feng , Zhang Han , Shen Dinggang
Published: August 2021

The detection of amyloid-β (Aβ) deposition in the brain provides crucial evidence in the clinical diagnosis of Alzheimer’s disease (AD). However, the efficiency of the current PET-based brain Aβ examination suffers from both coarse, visual inspection-based bi-class stratification and high scanning cost and risks. In this work, we explored the feasibility of using non-invasive functional magnetic resonance imaging (fMRI) to predict Aβ-PET phenotypes in the AD continuum with graph learning on brain networks. First, three whole-brain Aβ-PET phenotypes were identified through clustering and their association with clinical phenotypes were investigated. Second, both conventional and high-order functional connectivity (FC) networks were constructed using resting-state fMRI and the network topological architectures were learned with graph convolutional networks (GCNs) to predict such Aβ-PET phenotypes. The experiment of Aβ-PET phenotype prediction on 258 samples from the AD continuum showed that our algorithm achieved a high fMRI-to-PET prediction accuracy (78.8%). The results demonstrated the existence of distinguishable brain Aβ deposition phenotypes in the AD continuum and the feasibility of using artificial intelligence and non-invasive brain imaging technique to approximate PET-based evaluations. It can be a promising technique for high-throughput screening of AD with less costs and restrictions.
Population impact of SARS-CoV-2 variants with enhanced transmissibility and/or partial immune escape
Authors: Bushman Mary , Kahn Rebecca , Taylor Bradford P. , Lipsitch Marc , Hanage William P.
Published: August 2021

SARS-CoV-2 variants of concern exhibit varying degrees of transmissibility and, in some cases, escape from infection- and vaccine-induced immunity. Much effort has been devoted to measuring these phenotypes, but predicting their impact on the course of the pandemic – especially that of immune escape – remains a challenge. Here, we use a mathematical model to simulate the dynamics of wildtype and variant strains of SARS-CoV-2 in the context of vaccine rollout and nonpharmaceutical interventions. We show that variants with enhanced transmissibility easily rise to high frequency, whereas partial immune escape, on its own, often fails to do so. However, when these phenotypes are combined, enhanced transmissibility can carry the variant to high frequency, at which point partial immune escape may limit the ability of vaccination to control the epidemic. Our findings suggest that moderate immune escape poses a low risk unless combined with a substantial increase in transmissibility.
Child and caregiver mental health during 12 months of the COVID-19 pandemic in Australia: findings from national repeated cross-sectional surveys
Authors: Price Anna M. H. , Measey Mary-Anne , Hoq Monsurul , Rhodes Anthea , Goldfeld Sharon
Published: August 2021

Background

There are calls for research into the mental health consequences of living through the COVID-19 pandemic. Australia’s initial, effective suppression of COVID-19 offers insights into these indirect impacts in the relative absence of the disease. We aimed to describe the mental health experiences of Australian caregivers and children over 12 months, reporting differences related to demographic, socioeconomic and lockdown characteristics.

Methods

Data were from Australia’s only nationally representative, repeated cross-sectional survey of caregivers with children (0-17 years). N=2020 caregivers participated in June 2020, N=1434 in September 2020, and N=2508 in July 2021. Caregivers reported their mental health (poor versus not, Kessler-6), and perceived impacts of the pandemic on theirs and their children’s mental health (negative versus none/positive). Data were weighted to approximate population distributions of caregiver age, gender, sole-caregiving, number and ages of children, state/territory and neighbourhood-level disadvantage.

Results

Perceived impacts on mental health were more frequently negative for female (versus male) caregivers and older (versus younger) children. Poor caregiver mental health (K6) was more common for families experiencing socioeconomic adversity (especially financial), while perceived impacts were more frequently negative for more socially advantaged groups. Caregivers who experienced the least total lockdown reported similar K6 over time. Otherwise, poor mental health and perceived negative impacts increased over time with increasing total length of lockdown.

Conclusion

Despite Australia’s low infection rates, the negative mental health experiences of the COVID-19 pandemic are real and concerning. Addressing poor mental health must be central to ongoing pandemic recovery efforts for families and children.

What is known about this topic?

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The global evidence shows that, for general adult populations, psychological distress peaked in the first months of the COVID-19 pandemic before appearing to improve.

-

Less is known about mental health over time of living through the pandemic, especially for caregivers and children. There are urgent calls for research.

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Due to low infection rates, Australia’s experience can provide insight into the mental health impacts of lockdown with minimal compounding harms of the virus.

What this study adds

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From June 2020 to July 2021, Australia’s lockdowns were detrimental for caregiver and child mental health.

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Negative mental health experiences differed by caregiver gender, child age and family socioeconomic characteristics.

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Pandemic response and recovery planning must consider both family mental health and socioeconomic security.
Genome-wide meta-analysis and omics integration identifies novel genes associated with diabetic kidney disease
Authors: Sandholm Niina , Cole Joanne B , Nair Viji , Sheng Xin , Liu Hongbo , Ahlqvist Emma , van Zuydam Natalie , Dahlström Emma H , Fermin Damian , Smyth Laura J , Salem Rany M , Forsblom Carol , Valo Erkka , Harjutsalo Valma , Brennan Eoin P , McKay Gareth , Andrews Darrell , Doyle Ross , Looker Helen C , Nelson Robert G , Palmer Colin , McKnight Amy Jayne , Godson Catherine , Maxwell Alexander P , Groop Leif , McCarthy Mark I , Kretzler Matthias , Susztak Katalin , Hirschhorn Joel N , Florez Jose C , Groop Per-Henrik ,   for the GENIE Consortium
Published: August 2021

Background

Diabetes is the leading cause of kidney disease, and heritability studies demonstrate a substantial, yet poorly understood, contribution of genetics to kidney complications in people with diabetes.

Methods

We performed genome-wide association study (GWAS) meta-analyses using ten different phenotypic definitions of diabetic kidney disease (DKD), including nearly 27,000 individuals with diabetes, and integrated the results with various kidney omics datasets.

Results

The meta-analysis identified a novel low frequency intronic variant (rs72831309) in the TENM2 gene encoding teneurin transmembrane protein 2 associated with a lower risk of the combined chronic kidney disease (CKD; eGFR<60 ml/min/1.73 m2) and DKD (microalbuminuria or worse) phenotype (“CKD-DKD”, odds ratio 2.08, p=9.8×10−9). Gene-level analysis identified ten genes associated with DKD (COL20A1, DCLK1, EIF4E, PTPRN-RESP18, GPR158, INIP-SNX30, LSM14A, and MFF, p<2.7×10−6). Integration of GWAS data with human glomerular and tubular expression data in a transcriptome-wide association study demonstrated higher tubular AKIRIN2 gene expression in DKD versus non-DKD controls (p=1.1×10−6). The lead SNPs within the DCLK1, AKIRIN2, SNX30 and three other gene regions significantly alterated the methylation at this region in kidneys (p<2.2×10−11). Expression of target genes in kidney tubules or glomeruli correlated with relevant pathological phenotypes. For example, tubular TENM2 expression positively correlated with eGFR (p=2.3×10−9) and negatively with tubulointerstitial fibrosis (p=4.7×10−9), tubular DCLK1 expression positively correlated with fibrosis (p=1.6×10−12), and SNX30 level positively correlated with eGFR (p=7.6×10−13) and negatively with fibrosis (p<2×10−16).

Conclusions

GWAS meta-analysis and integration with renal omics data points to novel genes contributing to pathogenesis of DKD.
Highly valued despite burdens: qualitative implementation research on rapid tests for hospital-based SARS-CoV-2 screening
Authors: Wachinger Jonas , McMahon Shannon A. , Lohmann Julia , De Allegri Manuela , Denkinger Claudia M.
Published: August 2021

Antigen-based rapid diagnostic tests (RDTs) for SARS-CoV-2 have good reliability and have been repeatedly implemented as part of pandemic response policies, especially for screening in high-risk settings (e.g., hospitals and care homes) where fast recognition of an infection is essential, but evidence from actual implementation efforts is lacking.

We conducted a prospective qualitative study at a large tertiary care hospital in Germany where RDTs are used to screen incoming patients. We relied on semi-structured observations of the screening situation, as well as on 30 in-depth interviews with hospital staff (members of the regulatory body, department heads, staff working on the wards, staff training providers on how to perform RDTs, and providers performing RDTs as part of the screening) and patients being screened with RDTs.

Despite some initial reservations, RDTs were rapidly accepted and adopted as the best available tool for accessible and reliable screening. Decentralized implementation efforts resulted in different procedures being operationalized across departments. Procedures were continuously refined based on initial experiences (e.g., infrastructural or scheduling constraints), pandemic dynamics (growing infection rates), and changing regulations (e.g., screening of all external personnel). To reduce interdepartmental tension, stakeholders recommended high-level, consistently communicated and enforced regulations.

Despite challenges, RDT-based screening for all incoming patients was observed to be feasible and acceptable among implementers and patients, and merits continued consideration in the context of rising infections and stagnating vaccination rates.
Early immune responses have long-term associations with clinical, virologic, and immunologic outcomes in patients with COVID-19
Authors: Hu Zicheng , van der Ploeg Kattria , Chakraborty Saborni , Arunachalam Prabhu , Mori Diego Martinez , Jacobson Karen B. , Bonilla Hector , Parsonnet Julie , Andrews Jason , Hedlin Haley , de la Parte Lauren , Dantzler Kathleen , Ty Maureen , Tan Gene S , Blish Catherine A. , Takahashi Saki , Rodriguez-Barraquer Isabel , Greenhouse Bryan , Butte Atul J. , Singh Upinder , Pulendran Bali , Wang Taia T. , Jagannathan Prasanna
Published: August 2021

The great majority of SARS-CoV-2 infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, mild to moderate infections are an important contributor to ongoing transmission. There remains a critical need to identify host immune biomarkers predictive of clinical and virologic outcomes in SARS-CoV-2-infected patients. Leveraging longitudinal samples and data from a clinical trial of Peginterferon Lambda for treatment of SARS-CoV-2 infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients within the first 2 weeks of symptom onset. We define early immune signatures, including plasma levels of RIG-I and the CCR2 ligands (MCP1, MCP2 and MCP3), associated with control of oropharyngeal viral load, the degree of symptom severity, and immune memory (including SARS-CoV-2-specific T cell responses and spike (S) protein-binding IgG levels). We found that individuals receiving BNT162b2 (Pfizer–BioNTech) vaccine had similar early immune trajectories to those observed in this natural infection cohort, including the induction of both inflammatory cytokines (e.g. MCP1) and negative immune regulators (e.g. TWEAK). Finally, we demonstrate that machine learning models using 8-10 plasma protein markers measured early within the course of infection are able to accurately predict symptom severity, T cell memory, and the antibody response post-infection.
mRNA vaccines effectiveness against COVID-19 hospitalizations and deaths in older adults: a cohort study based on data-linkage of national health registries in Portugal
Authors: Nunes Baltazar , Rodrigues Ana Paula , Kislaya Irina , Cruz Camila , Peralta-Santos André , Lima João , Leite Pedro Pinto , Sequeira Duarte , Dias Carlos Matias , Machado Ausenda
Published: August 2021

Background

We used electronic health registries to estimate the mRNA vaccine effectiveness (VE) against COVID-19 hospitalizations and deaths in older adults.

Methods

We established a cohort of individuals aged 65 and more years, resident in Portugal mainland through data linkage of eight national health registries. For each outcome, VE was computed as one minus the confounder-adjusted hazard ratio, estimated by time-dependent Cox regression.

Results

VE against COVID-19 hospitalization ≥14 days after the second dose was 94% (95%CI 88 to 97) for age-group 65-79 years old (yo) and 82% (95%CI 72 to 89) for ≥80 yo. VE against COVID-19 related deaths ≥ 14 days after second dose was 96% (95%CI 92 to 98) for age-group 65-79 yo and 81% (95%CI 74 to 87), for ≥80 yo individuals. No evidence of VE waning was observed after 98 days of second dose uptake.

Conclusions

mRNA vaccine effectiveness was high for the prevention of hospitalizations and deaths in age-group 65-79 yo and ≥80 yo with a complete vaccination scheme, even after 98 days of second dose uptake.
Predictors of eviction and quality of tenant-landlord relationships during the 2020-2021 eviction moratorium in the U.S.
Authors: Tsai Jack , Huang Minda , Blosnich John R. , Elbogen Eric B.
Published: August 2021

In 2020, the Centers for Disease Control and Prevention (CDC) issued several agency orders that put into effect a national moratorium on evictions for over one year to limit transmission of Coronavirus Disease 2019 (COVID-19). Little is known about landlord and tenant behaviors during the eviction moratorium. The current study used three waves of data from May 2020-April 2021 from a nationally representative sample of U.S. middle- and low-income tenants (n= 3,393 in Wave 1, n= 1,311 in Wave 2, and 814 in Wave 3) to examine tenants who were evicted during the eviction moratorium and the reported effects of the moratorium on tenant rental payments and tenant-landlord relationships. Across three Waves, 4.3% of tenants reported experiencing an eviction during the moratorium and 6-23% of tenants reported delaying paying rent because of the moratorium. Multivariable analyses found that tenants who delayed paying their rent, were female, or had a history of mental illness or substance use disorder were significantly more likely to report the eviction moratorium had a negative effect on the relationship with their landlord. Analyses also revealed that testing positive for COVID-19 was not a significant predictor of eviction but tenants with a history a homelessness were more than 9 times as likely to report an eviction than those without such a history. Together, these findings suggest the eviction moratorium has had some unintended consequences on rent payments and tenant-landlord relationships that need to be considered in the aftermath of the COVID-19 pandemic.
Analysis of daily reproduction rates of COVID-19 using Current Health Expenditure as Gross Domestic Product percentage (CHE/GDP) across countries
Authors: Oshinubi Kayode , Rachdi Mustapha , Demongeot Jacques
Published: August 2021

(1)

Background

Impact and severity of coronavirus pandemic on health infrastructure vary across countries. We examine the role percentage health expenditure plays in various countries in terms of their preparedness and see how countries improved their public health policy in the first and second wave of the coronavirus pandemic;

(2)

Methods

We considered the infectious period during the first and second wave of 195 countries with their Current Health Expenditure as Gross Domestic Product percentage (CHE/GDP). Exponential model was used to calculate the slope of the regression line while the ARIMA model was used to calculate the initial autocorrelation slope and also to forecast new cases for both waves. The relationship between epidemiologic and CHE/GDP data was used for processing ordinary least square multivariate modeling and classifying countries into different groups using PC analysis, K-means and Hierarchical clustering;

(3)

Results

Results show that some countries with high CHE/GDP improved their public health strategy against virus during the second wave of the pandemic;

(4)

Conclusions

Results revealed that countries who spend more on health infrastructure improved in the tackling of the pandemic in the second wave as they were worst hit in the first wave. This research will help countries to decide on how to increase their CHE/GDP in order to tackle properly other pandemic waves of the present Covid-19 outbreak and future diseases that may occur. We are also opening up a debate on the crucial role socio-economic determinants play during the exponential phase of the pandemic modelling.
A Systematic Review of the Protective Effect of Prior SARS-CoV-2 Infection on Repeat Infection
Authors: Kojima N , Shrestha NK , Klausner JD
Published: August 2021

Introduction

We systematically reviewed studies to estimate the risk of SARS-CoV-2 reinfection among those previously infected with SARS-CoV-2.

Methods

For this systematic review, we searched scientific publications on PubMed and, the pre-print server, MedRxiv through August 18, 2021. Eligible studies were retrieved on August 18, 2021. We used the following search term on PubMed: (((“Cohort Studies”[Majr]) AND (“COVID-19”[Mesh] OR “SARS-CoV-2”[Mesh])) OR “Reinfection”[Majr]) OR “Reinfection”[Mesh]. We used the following search term on MedRxiv: “Cohort Studies” AND “COVID-19” OR “SARS-CoV-2” AND “Reinfection”. The search terms were broad to encompass all possibilities for applicable studies. There were no restrictions on the date of publication. Studies that did not describe cohorts with estimates of the risk of SARS-CoV-2 reinfection among those with previous infection were excluded. Studies that included vaccinated participants were either excluded or limited to sub-groups of non-vaccinated individuals. To identify relevant studies with appropriate control groups, we developed the following criteria for studies to be included in the systematic analysis: (1) baseline polymerase chain reaction (PCR) testing, (2) a negative comparison group, (3) longitudinal follow-up, (4) a cohort of human participants, i.e., not a case report or case series, and (5) outcome determined by PCR. The review was conducted following PRISMA guidelines. We assessed for selection, information, and analysis bias, per PRISMA guidelines.

Results

We identified 1,392 reports. Of those, 10 studies were eligible for our systematic review. The weighted average risk reduction against reinfection was 90.4% with a standard deviation of 7.7%. Protection against SARS-CoV-2 reinfection was observed for up to 10 months. Studies had potential information, selection, and analysis biases.

Conclusions

The protective effect of prior SARS-CoV-2 infection on re-infection is high and similar to the protective effect of vaccination. More research is needed to characterize the duration of protection and the impact of different SARS-CoV-2 variants.