bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of natural selection in producing optimal sex ratio adjustments in a fig wasp species
Authors: Greeff Jaco M. , Pentz Karina , Warren Marié
Published: September 2020

Ever since Darwin's discovery of natural selection, we expect traits to evolve to increase organisms' fitness. As a result, we can use optimization models to make
a priori
predictions of phenotypic variation, even when selection is frequency-dependent. A notable example is the prediction of female-biased sex ratios resulting from local mate competition (LMC) and inbreeding. LMC models incorporate the effects of LMC and inbreeding. Fig wasp sex ratio adjustments fit LMC predictions well. However, the appropriateness of LMC models to fig wasps has been questioned, and the role that a coincidental by-product plays in creating the apparent fit has been clearly illustrated. Here, we show that the sex ratio adjustments of a fig wasp are the result of a dual mechanism. It consists of a standard facultative LMC response favoured by natural selection, as well as a mechanism that may be the result of selection, but that could also be a coincidental by-product. If it is a by-product, the fitness increase is coincidental and natural selection's role was limited to fine-tuning it for higher fitness returns. We further document a case of an apparent fitness-reducing sex ratio adjustment. We conclude that the use of the adaptationist approach demands that our understanding of traits must be remodelled continually to rectify spurious assumptions.
Influenza A viruses remain infectious for more than seven months in northern wetlands of North America
Authors: Ramey Andrew M. , Reeves Andrew B. , Drexler Judith Z. , Ackerman Joshua T. , De La Cruz Susan , Lang Andrew S. , Leyson Christina , Link Paul , Prosser Diann J. , Robertson Gregory J. , Wight Jordan , Youk Sungsu , Spackman Erica , Pantin-Jackwood Mary , Poulson Rebecca L. , Stallknecht David E.
Published: September 2020

In this investigation, we used a combination of field- and laboratory-based approaches to assess if influenza A viruses (IAVs) shed by ducks could remain viable for extended periods in surface water within three wetland complexes of North America. In a field experiment, replicate filtered surface water samples inoculated with duck swabs were tested for IAVs upon collection and again after an overwintering period of approximately 6–7 months. Numerous IAVs were molecularly detected and isolated from these samples, including replicates maintained at wetland field sites in Alaska and Minnesota for 181–229 days. In a parallel laboratory experiment, we attempted to culture IAVs from filtered surface water samples inoculated with duck swabs from Minnesota each month during September 2018–April 2019 and found monthly declines in viral viability. In an experimental challenge study, we found that IAVs maintained in filtered surface water within wetlands of Alaska and Minnesota for 214 and 226 days, respectively, were infectious in a mallard model. Collectively, our results support surface waters of northern wetlands as a biologically important medium in which IAVs may be both transmitted and maintained, potentially serving as an environmental reservoir for infectious IAVs during the overwintering period of migratory birds.
Stool banking for fecal microbiota transplantation: methods and operations at a large stool bank
Authors: Chen Justin , Zaman Amanda , Ramakrishna Bharat ,   OpenBiome Team, Olesen Scott W.
Published: September 2020

Objectives

Fecal microbiota transplantation (FMT) is a recommended therapy for recurrentClostridioides difficileinfection and is being investigated as a potential therapy for dozens of microbiome-mediated indications. Stool banks centralize FMT donor screening and FMT material preparation with the goal of improving the safety, quality, convenience, and accessibility of FMT material. Although there are published consensuses on donor screening guidelines, there are few reports about the implementation of those guidelines in functioning stool banks.

Methods

To help inform consensus standards with data gathered from real-world settings and, in turn, to improve patient care, here we describe the general methodology used in 2018 by OpenBiome, a large stool bank, and its outputs in that year.

Results

In 2018, the stool bank received 7,536 stool donations from 210 donors, a daily average of 20.6 donations, and processed 4,271 of those donations into FMT preparations. The median time a screened and enrolled stool donor actively donated stool was 5.8 months. The median time between the manufacture of an FMT preparation and its shipment to a hospital or physician was 8.9 months. Half of the stool bank’s partner hospitals and physicians ordered an average of 0.75 or fewer FMT preparations per month.

Conclusions

Further knowledge sharing should help inform refinements of stool banking guidelines and best practices.
Run for your life – an integrated virtual tissue platform for incorporating exercise oncology into immunotherapy
Authors: Serrano Josua Aponte , Hagar Amit
Published: September 2020

The purpose of this paper is to introduce a novelin silicoplatform for simulating early stage solid tumor growth and anti-tumor immune response. We present the model, test the sensitivity and robustness of its parameters, and calibrate it with clinical data from exercise oncology experiments which offer a natural biological backdrop for modulation of anti-tumor immune response. We then perform two virtual experiments with the model that demonstrate its usefulness in guiding pre-clinical and clinical studies of immunotherapy. The first virtual experiment describes the intricate dynamics in the tumor microenvironment between the tumor and the infiltrating immune cells. Such dynamics is difficult to probe during a pre-clinical study as it requires significant redundancy in lab animals and is prohibitively time-consuming and labor-intensive. The result is a series of spatiotemporal snapshots of the tumor and its microenvironment that can serve as a platform to test mechanistic hypotheses on the role and dynamics of different immune cells in anti-tumor immune response. The second virtual experiment shows how dosage and/or frequency of immunotherapy drugs can be optimized based on the aerobic fitness of the patient, so that possible adverse side effects of the treatment can be minimized.
Effects of age on goal-dependent modulation of episodic memory retrieval
Authors: Srokova Sabina , Hill Paul F. , Elward Rachael L. , Rugg Michael D.
Published: September 2020

Retrieval gating refers to the ability to modulate the retrieval of features of a single memory episode according to behavioral goals. Recent findings demonstrate that younger adults engage retrieval gating by attenuating the representation of task-irrelevant features of an episode. Here, we examine whether retrieval gating varies with age. Younger and older adults incidentally encoded words superimposed over scenes or scrambled backgrounds that were displayed in one of three spatial locations. Participants subsequently underwent fMRI as they completed two memory tasks: the background task, which tested memory for the word’s background, and the location task, testing memory for the word’s location. Employing univariate and multivariate approaches, we demonstrated that younger, but not older adults, exhibited attenuated reinstatement of scene information when it was goal-irrelevant (during the location task). Additionally, in younger adults only, the strength of scene reinstatement in the parahippocampal place area during the background task was related to item and source memory performance. Together, these findings point to an age-related decline in the ability to engage retrieval gating.
ClinePlotR: Visualizing genomic clines and detecting outliers in R
Authors: Martin Bradley T. , Chafin Tyler K. , Douglas Marlis R. , Douglas Michael E.
Published: September 2020

Patterns of multi-locus differentiation (i.e., genomic clines) often extend broadly across hybrid zones and their quantification can help diagnose how species boundaries are shaped by adaptive processes, both intrinsic and extrinsic. In this sense, the transitioning of loci across admixed individuals can be contrasted as a function of the genome-wide trend, in turn allowing an expansion of clinal theory across a much wider array of biodiversity. However, computational tools that serve to interpret and consequently visualize ‘genomic clines’ are limited. Here, we introduce the ClinePlotR R-package for visualizing genomic clines and detecting outlier loci using output generated by two popular software packages,bgcand Introgress. ClinePlotR bundles both input generation (i.e, filtering datasets and creating specialized file formats) and output processing (e.g., MCMC thinning and burn-in) with functions that directly facilitate interpretation and hypothesis testing. Tools are also provided for post-hoc analyses that interface with external packages such as ENMevaland RIdeogram. Our package increases the reproducibility and accessibility of genomic cline methods, thus allowing an expanded user base and promoting these methods as mechanisms to address diverse evolutionary questions in both model and non-model organisms.
Population receptive fields in non-human primates from whole-brain fMRI and large-scale neurophysiology in visual cortex
Authors: Klink P. Christiaan , Chen Xing , Vanduffel Wim , Roelfsema Pieter R.
Published: September 2020

Population receptive field (pRF) modeling is a popular fMRI method to map the retinotopic organization of the human brain. While fMRI-based pRF-maps are qualitatively similar to invasively recorded single-cell receptive fields in animals, it remains unclear what neuronal signal they represent. We addressed this question in awake non-human primates comparing whole-brain fMRI and large-scale neurophysiological recordings in areas V1 and V4 of the visual cortex. We examined the fits of several pRF-models based on the fMRI BOLD-signal, multi-unit spiking activity (MUA) and local field potential (LFP) power in different frequency bands. We found that pRFs derived from BOLD-fMRI were most similar to MUA-pRFs in V1 and V4, while pRFs based on LFP gamma power also gave a good approximation. FMRI-based pRFs thus reliably reflect neuronal receptive field properties in the primate brain. In addition to our results in V1 and V4, the whole-brain fMRI measurements revealed retinotopic tuning in many other cortical and subcortical areas with a consistent increase in pRF-size with increasing eccentricity, as well as a retinotopically specific deactivation of default-mode network nodes similar to previous observations in humans.
Polygenic Risk Scores for Kidney Function to the Circulating Proteome, and Incident Kidney Diseases: the Atherosclerosis Risk in Communities Study
Authors: Yu Zhi , Jin Jin , Tin Adrienne , Köttgen Anna , Yu Bing , Chen Jingsha , Surapaneni Aditya , Zhou Linda , Ballantyne Christie M. , Hoogeveen Ron C. , Arking Dan E. , Chatterjee Nilanjan , Grams Morgan E. , Coresh Josef
Published: September 2020

Genome-wide association studies (GWAS) have revealed numerous loci for kidney function (estimated glomerular filtration rate, eGFR). The relationship of polygenic predictors of eGFR, risk of incident adverse kidney outcomes, and the plasma proteome is not known. We developed a genome-wide polygenic risk score (PRS) using a weighted average of 1.2 million SNPs for eGFR using the LDpred algorithm, summary statistics generated by a European-ancestry (EA) meta-analysis of the CKDGen Consortium (N=558,423) and UK Biobank GWAS for eGFR (90% of the cohort; N=289,432), followed by best parameter selection using data from the remaining 10% of the UK Biobank (N=32,159). We then tested the association of the PRS among 8,886 EA participants in the Atherosclerosis Risk in Communities (ARIC) study (mean age: 54±6 years, 53% female) with incident chronic kidney disease (CKD), end stage kidney disease (ESKD), kidney failure (KF), and acute kidney injury (AKI). We also examined 4,877 plasma proteins measured at two time points (visit 3 (1993-95) and visit 5 (2011-13)) in relation to the PRS and compared associations between the proteome and eGFR itself. All models were adjusted for age, sex, center, and the first 10 principal components of ancestry. The developed PRS had an R2for eGFR of 0.07 in ARIC. Over 30 years of follow up, the number of incident CKD, ESKD, KF, and AKI were 2,959, 137, 470, and 1,723, respectively. The PRS showed significant associations with all outcomes: hazard ratios (95% CI) per 1 SD lower PRS were 1.33 (1.28, 1.39), 1.20 (1.00, 1.42), 1.17 (1.06, 1.28), and 1.07 (1.02, 1.12) for incident CKD, ESKD, KF, and AKI respectively. The PRS was significantly associated (Bonferroni threshold P<1.02 × 10−5) with 108 proteins at both time points. The strongest associations were with cystatin-C (a marker of kidney function used in clinical practice), collagen alpha-1 (XV) chain, and desmocollin-2. All significant correlations with the PRS were negative, except those of testican-2 and angiostatin. Correlations of proteins with eGFR were much stronger than those with the PRS. Overall, we demonstrated that the PRS for eGFR is now sufficiently strong to capture risk for a spectrum of incident kidney diseases as well as broadly influence the plasma proteome.
A Spatiotemporal Molecular Switch Governs Plant Asymmetric Cell Division
Authors: Guo Xiaoyu , Park Chan Ho , Wang Zhi-Yong , Nickels Bryce E. , Dong Juan
Published: September 2020

Asymmetric cell division (ACD) often requires protein polarization in the mother cell to produce daughter cells with distinct identities (“cell-fate asymmetry”). Here, we define a previously undocumented mechanism for establishing cell-fate asymmetry inArabidopsisstomatal stem cells. In particular, we show that polarization of BSL protein phosphatases promotes stomatal ACD by establishing a “kinase-based signaling asymmetry” in the two daughter cells. BSL polarization in the stomatal ACD mother cell is triggered upon commitment to cell division. Polarized BSL is inherited by the differentiating daughter cell where it suppresses cell division and promotes cell-fate determination. Plants lacking BSL exhibit stomatal over-proliferation, demonstrating BSL plays an essential role in stomatal development. Our findings establish that BSL polarization provides a spatiotemporal molecular switch that enables cell-fate asymmetry in stomatal ACD daughter cells. We propose BSL polarization is triggered by an ACD “checkpoint” in the mother cell that monitors establishment of division-plane asymmetry.
Household transmission in people infected with SARS-CoV-2 (COVID-19) in Metropolitan Lima
Authors: Angulo-Bazan Yolanda , Solis Gilmer , Cardenas Fany , Jorge Ana , Acosta Joshi , Cabezas Cesar
Published: September 2020

Objective

Describe the characteristics of SARS-CoV-2 infection among household members with a confirmed primary case of COVID-19 in low burden districts in Metropolitan Lima.

Materials and Methods

A retrospective, secondary database review study was conducted. The information was collected from an epidemiological surveillance activity in close contacts (co-inhabitants) in 52 households in Metropolitan Lima with only one member with COVID-19. A reevaluation was carried out in 10 households. Epidemiological and clinical variables were evaluated and its association with the result of the rapid serological test (presence of IgG, IgM or both).

Results

Secondary cases were found in 40 households, which represents an average of 49.9% identification per household. A secondary attack rate of 53.0% (125 cases) was found among cohabitants, with 77.6% of cases being symptomatic (symptomatic / asymptomatic ratio: 3.5). The presence of fever and / or chills was found in 40.0% of people with a positive result, followed by a sore throat, in 39.2%. Ageusia and anosmia were present in 22.4% and 20.8% of cases, respectively. A reevaluation in 40 family members 33.6 ± 2.7 days after the first evaluation, show the persistence of positive IgM and IgG in the 20 positive cases in the first evaluation.

Conclusion

Having a primary case of COVID-19 in home, the secondary attack rate of this infection is 53%; however, in a significant proportion of households evaluated there was no positive case, beyond the primary case. The epidemiological and clinical characteristics found in this case were in accordance with what has already been reported in other international series.
Efficiency ofSalicornia neeito treat aquaculture effluent from a hypersaline and artificial wetland
Authors: Diaz Mónica R. , Araneda Javier , Osses Andrea , Orellana Jaime , Gallardo José A.
Published: September 2020

In this study we evaluated the potential ofSalicornia neei, a halophyte plant native to South America, to treat saline effluents with simulated concentration of ammonium-N (Amm) and nitrate-N (Nit) similar to land-based marine aquaculture effluents. Plants were cultivated for 74 days in drainage lysimeters under three treatments of seawater fertilized with: 1) Nit+Amm, 2) Nit, or 3) without fertilizer (Control). Over 5 repetitions, nitrogen removal efficiency (RE) was high in both treatments (Nit + Amm = 89.6± 1,0 %; Nit 88.8 ± 0.9 %). While nitrogen removal rate (RR) was non linear and concentration-dependent (RRday 1-4: Nit+Amm= 2.9 ± 0.3 mg L−1d−1, Nit = 2.4 ± 0.5mg L−1d−1; RRday5-8: Nit + Amm = 0.8 ± 0.2mg L−1d−1, Nit=1.0 ± 0.2mg L−1d−1). Effluent salinity increased from 40.6 to 49.4 g L−1during the experiment, with no observed detrimental effects on RE or RR. High nitrogen removal efficiency and significant biomass production observed, Nit+Amm = 11.3 ± 2.0 kg m−2; Nit = 10.0 ± 0.8 kg m−2; Control = 4.6 ± 0.6 kg m−2, demonstrate that artificial wetlands ofS. neeican be used for wastewater treatment in saline aquaculture in South America.
Multivariate pattern analysis of brain structure predicts functional outcome after auditory-based cognitive training interventions
Authors: Kambeitz-Ilankovic Lana , Vinogradov Sophia , Wenzel Julian , Fisher Melissa , Haas Shalaila S. , Betz Linda , Penzel Nora , Nagarajan Srikantan , Koutsouleris Nikolaos , Subramaniam Karuna
Published: September 2020

Background

Cognitive gains following cognitive training interventions (CT) are associated with improved functioning in people with schizophrenia (SCZ). However, considerable inter-individual variability is observed. Here, we evaluate the sensitivity of brain structural features to predict functional response to auditory-based cognitive training (ABCT) at a single subject level.

Methods

We employed whole-brain multivariate pattern analysis (MVPA) with support vector machine (SVM) modeling to identify grey matter (GM) patterns that predicted ‘higher’ vs. ‘lower’ functioning after 40 hours of ABCT at the single subject level in SCZ patients. The generalization capacity of the SVM model was evaluated by applying the original model through an Out-Of-Sample Cross Validation analysis (OOCV) to unseen SCZ patients from an independent sample that underwent 50 hours of ABCT.

Results

The whole-brain GM volume-based pattern classification predicted ‘higher’ vs. ‘lower’ functioning at follow-up with a balanced accuracy (BAC) of 69.4% (sensitivity 72.2%, specificity 66.7%) as determined by nested cross-validation. The neuroanatomical model was generalizable to an independent cohort with a BAC of 62.1% (sensitivity 90.9%, specificity 33.3%).

Conclusions

In particular, greater baseline GM volume in regions within superior temporal gyrus, thalamus, anterior cingulate and cerebellum -- predicted improved functioning at the single-subject level following ABCT in SCZ participants.
Phloem loading via the abaxial bundle sheath cells in maize leaves
Authors: Bezrutczyk Margaret , Zöllner Nora R. , Kruse Colin P. S. , Hartwig Thomas , Lautwein Tobias , Köhrer Karl , Frommer Wolf B. , Kim Ji-Yun
Published: September 2020

Leaves are asymmetric, with differential functionalization of abaxial and adaxial tissues. The bundle sheath (BS) surrounding the vasculature of the C3 crop barley is dorsoventrally differentiated into three domains: adaxial structural, lateral S-type, and abaxial L-type. S-type cells seem to transfer assimilates towards the phloem. Here we used single-cell RNA sequencing to investigate BS differentiation in C4 maize. Abaxial BS (abBS) cells of rank-2 intermediate veins specifically expressed three SWEET sucrose uniporters (SWEET13a, b, andc) and UmamiT amino acid efflux transporters.SWEET13a, b, cwere also identified in the phloem parenchyma (PP). Thus maize acquired a unique mechanism for phloem loading in whichabBS cells provide the main pathway for apoplasmic sucrose transfer towards the phloem. This pathway predominates in veins responsible for phloem loading (rank-2 intermediate), while rank-1 intermediate and major veins export sucrose from the phloem parenchyma (PP) adjacent to the sieve element companion cell (SE/CC) complex, as in Arabidopsis. We surmise thatabBS identity is subject to dorsoventral patterning and has components of PP identity. These observations provide first insights into the unique transport-specific properties ofabBS cells and support for a modification to the canonical phloem loading pathway of maize, which may be generalizable to other C4 monocots.
High spatial resolution global ocean metagenomes from Bio-GO-SHIP repeat hydrography transects
Authors: Larkin Alyse A. , Garcia Catherine A. , Brock Melissa L. , Lee Jenna A. , Garcia Nathan , Ustick Lucas J. , Barbero Leticia , Carter Brendan R. , Sonnerup Rolf E. , Talley Lynne , Tarran Glen A. , Volkov Denis L. , Martiny Adam C.
Published: September 2020

Detailed descriptions of microbial communities have lagged far behind physical and chemical measurements in the marine environment. Here, we present 720 globally distributed surface ocean metagenomes collected at high spatio-temporal resolution. Our low-cost metagenomic sequencing protocol produced 2.75 terabases of data, where the median number of base pairs per sample was 3.48 billion. The median distance between sampling stations was 26 km. The metagenomic libraries described here were collected as a part of a biological initiative for the Global Ocean Ship-based Hydrographic Investigations Program, or “Bio-GO-SHIP.” One of the primary aims of GO-SHIP is to produce high spatial and vertical resolution measurements of key state variables to directly quantify climate change impacts on ocean environments. By similarly collecting marine metagenomes at high spatiotemporal resolution, we expect that this dataset will help answer questions about the link between microbial communities and biogeochemical fluxes in a changing ocean.
Simplicial and Topological Descriptions of Human Brain Dynamics
Authors: Billings Jacob , Saggar Manish , Hlinka Jaroslav , Keilholz Shella , Petri Giovanni
Published: September 2020

Whereas brain imaging tools like functional Magnetic Resonance Imaging (fMRI) afford measurements of whole-brain activity, it remains unclear how best to interpret patterns found amid the data’s apparent self-organization. To clarify how patterns of brain activity support brain function, one might identify metric spaces that optimally distinguish brain states across experimentally defined conditions. Therefore, the present study considers the relative capacities of several metric spaces to disambiguate experimentally defined brain states. One fundamental metric space interprets fMRI data topographically, i.e, as the vector of amplitudes of a multivariate signal, changing with time. Another perspective considers the condition-dependency of the brain’s Functional Connectivity (FC), i.e., the similarity matrix computed across the variables of a multivariate signal. More recently, metric spaces that think of the data topologically, e.g., as an abstract geometric object, have become available. In the abstract, uncertainty prevails regarding the distortions imposed by the mode of measurement upon the object under study. Features that are invariant under continuous deformations, such as rotation and inflation, constitute the features of topological data analysis. While there are strengths and weaknesses of each metric space, we find that metric spaces that track topological features are optimal descriptors of the brain’s experimentally defined states.

AUTHOR SUMMARY

Time-Varying Functional Connectivity (TVFC) leverages brain imaging data to interpret brain function as time-varying patterns of coordinating activity among brain regions. While many questions remain regarding the organizing principles through which brain function emerges from multi-regional interactions, advances in the mathematics of Topological Data Analysis (TDA) may provide new insights into the brain’s functional self-organization. One tool from TDA, “persistent homology”, observes the occurrence and persistence ofn-dimensional holes in a sequence of simplicial complexes extracted from a weighted graph. The occurrence of such holes within the TVFC graph may indicate preferred routes of information flow among brain regions. In the present study, we compare the use of persistence homology versus more traditional metrics at the task of segmenting brain states that differ across experimental conditions. We find that the structures identified by persistence homology more accurately segment the stimuli, more accurately segment high versus low performance levels under common stimuli, and generalize better across volunteers. These findings support the topological interpretation of brain dynamics.
Biomechanical outcomes of the pendulum test characterize individual differences in activated versus resting leg rigidity in people with Parkinson’s disease
Authors: Martino Giovanni , McKay J. Lucas , Factor Stewart A. , Ting Lena H.
Published: September 2020

Leg rigidity is associated with frequent falls in people with Parkinson’s disease (PD), suggesting a potential role in functional balance and gait impairments. Changes in neural state due to secondary tasks, e.g. activation maneuvers, can exacerbate (or “activate”) rigidity, possibly increasing the risk of falls. However, the subjective interpretation and coarse classification of the standard clinical rigidity scale has prohibited the systematic, objective assessment of resting and activated leg rigidity. The pendulum test is an objective diagnostic method that we hypothesized would be sensitive enough to characterize resting and activated leg rigidity.

We recorded kinematic data during the pendulum test in 15 individuals with PD, spanning a range of leg rigidity severity (slight to severe). From the recorded data of leg swing kinematics we measured biomechanical outcomes including first swing excursion, first extension peak, number and duration of the oscillations, resting angle, relaxation index, maximum and minimum angular velocity. We examined associations between biomechanical outcomes and clinical leg rigidity score. We evaluated the effect of increasing rigidity through activation maneuvers on biomechanical outcomes. Finally, we assessed whether either biomechanical outcomes or changes in outcomes with activation were associated with fall history.

Our results suggest that the biomechanical assessment of the pendulum test can objectively quantify leg rigidity among people with PD. We found that the presence of marked rigidity during clinical exam significantly impacted biomechanical outcomes, i.e. first extension peak, number of oscillations, relaxation index and maximum angular velocity. No differences in the effect of activation maneuvers between groups with clinically assessed moderate and marked rigidity were observed, suggesting that activated rigidity may be independent of resting rigidity and should be scored as independent variables. Moreover, we found that fall history was more common among people whose rigidity was increased with a secondary task, as measured by biomechanical outcomes.

We conclude that different mechanisms contributing to resting and activated rigidity may play an important yet unexplored functional role in balance impairments. The pendulum test may contribute to a better understanding of fundamental mechanisms underlying motor symptoms in PD, evaluating the efficacy of treatments, and predicting the risk of falls.
Tracking Smell Loss to Identify Healthcare Workers with SARS-CoV-2 Infection
Authors: Weiss Julian J. , Attuquayefio Tuki N. , White Elizabeth B. , Li Fangyong , Herz Rachel S. , White Theresa L. , Campbell Melissa , Geng Bertie , Datta Rupak , Wyllie Anne L. , Grubaugh Nathan D. , Casanovas-Massana Arnau , Catherine Muenker M. , Handoko Ryan , Iwasaki Akiko ,   the Yale IMPACT Research Team, Martinello Richard A. , Ko Albert I. , Small Dana M. , Farhadian Shelli F.
Published: September 2020

Background

Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals, like HCW.

Methods

We performed a prospective cohort study, tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, novel behavioral at-home assessment of smell function with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and RT-qPCR testing to identify SARSCoV-2 infection.

Results

SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. Among the 17 infected HCW, 53% reported smell loss, and were more likely to report smell loss than COVID-negative HCW on both the at-home assessment and the screening questionnaire (P< .01). 67% reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among COVID-positive HCW who reported smell loss (P< .01).

Conclusions

In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of COVID-19 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.
An epithelial microRNA upregulates airway IL-25 and TSLP expression in type 2-high asthma via targeting CD39-extracellular ATP axis
Authors: Zhang Kan , Feng Yuchen , Liang Yuxia , Wu Wenliang , Chang Chenli , Chen Dian , Chen Shengchong , Yi Lingling , Zhen Guohua
Published: September 2020

The presence of type 2 inflammation is a prominent endotype of asthma. Airway epithelial cell-derived cytokines IL-25, IL-33 and TSLP initiate type 2 inflammation. However, the upstream signaling pathway regulating these cytokines’ expression remains elusive. We identified a small set of epithelial microRNAs differentially expressed between type 2-low and –high asthma patients. MiR-206 was the most highly expressed microRNA in type 2-high asthma relative to type 2-low asthma, but was downregulated in both asthma subsets compared to control subjects. CD39, an ecto-nucleotidase degrading extracellular ATP, was a target of miR-206 and upregulated in asthma. In cultured human bronchial epithelial cells, allergen-induced rapid accumulation of extracellular ATP was responsible for miR-206 downregulation and CD39 upregulation, suggesting a protective mechanism to eliminate excessive ATP. Importantly, BALF ATP levels were increased in asthma patients, and strongly correlated with elevated IL-25 and TSLP expression in type 2-high asthma. Intriguingly, inhibition of airway miR-206 increased Cd39 expression, suppressed airway ATP accumulation and Il-25, Il-33, Tslp expression, and alleviated type 2 inflammation in a mouse model of asthma. In contrast, airway miR-206 overexpression had opposite effects. Taken together, airway epithelial miR-206 upregulates IL-25, TSLP expression via targeting CD39-extracellular ATP axis in type 2-high asthma.
Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection: A Spanish, Multicenter, Cohort Study
Authors: Ruiz-Antorán Belén , Sancho-López Aránzazu , Torres MD Ferrán , Concha Víctor Moreno-Torres , de Abechuco Itziar de Pablo López , López Paulina García , Abad-Santos Francisco , Fernández Clara María Rosso , Aldea-Perona Ana , Montané Eva , Aparicio-Hdez Ruth M. , LLop Rius Roser , Pedrós Consuelo , Gijón Paloma , Carballo Carolina Hernández , Martínez María José Pedrosa , Jiménez Consuelo Rodríguez , Prada-Ramallal Guillermo , García Lourdes Cabrera , García Josefa Andrea Aguilar , Sanjuan-Jimenez Rocío , Barraza Evelyn Iveth Ortiz , Sánchez-Chica Enrique , Fernández-Cruz Ana
Published: September 2020

Background

We aimed to determine the impact of tocilizumab use in severe COVID-19 pneumonia mortality.

Methods

We performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain, from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by Inverse Probability of the Treatment Weights (IPTW). Tocilizumab effect in patients receiving steroids during the 48h following inclusion was analyzed.

Results

During the study period, 506 patients with severe COVID-19 fulfilled inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days (IQR 8-14). Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls (16.8% versus 31.5%, HR 0.514 [95CI 0.355-0.744], p< 0.001; weighted HR 0.741 [95CI 0.619-0.887], p = 0.001). Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment (RRR 46.7%). We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in patients treated with tocilizumab than in those treated with steroids alone (10.9% versus 40.2%, HR 0.511 [95CI 0.352-0.741], p = 0.036; weighted HR 0.6 [95CI 0.449-0.804], p< 0.001) (Interaction p = 0.094).

Conclusions

These results show that survival of patients with severe COVID-19 is higher in patients treated with tocilizumab than in those not treated, and that tocilizumab effect adds to that of steroids administered to non-intubated cases with COVID-19 during the first 48 hours of presenting with respiratory failure despite of oxygen therapy. Randomised controlled studies are needed to confirm these results.

We investigated in-hospital mortality of patients with severe SARS-CoV-2 pneumonia in a multicenter series of patients treated with tocilizumab compared to controls, and adjusted using IPTW. Our results show a beneficial impact of tocilizumab treatment in SARS-CoV-2 pneumonia, that adds to that of steroids.
COVID-19 in patients with hepatobiliary and pancreatic diseases: A single-centre cross-sectional study in East London
Authors: Ullah Abu Z M Dayem , Sivapalan Lavanya , Kocher Hemant M , Chelala Claude
Published: September 2020

Objective

To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions.

Design

Cross-sectional study.

Setting

East London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) study at Barts Health NHS Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥ 18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020.

Participants

EL-PaC-Epidem study participants, alive on 12 February 2020, and living in East London within the previous six months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background.

Main outcome measure

COVID-19 incidence and mortality.

Results

Some 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with an increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance mis-users were at more risk of infection, so were patients on Vitamin D treatment. The higher odds ratios in patients with chronic pancreatic or mild liver conditions, age>70, and history of smoking or obesity were due to co-existing comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19).

Conclusions

In this large population-based study of HPB patients, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multi-morbidities, substance mis-use, and a history of Vitamin D treatment independently posed higher odds of acquiring COVID-19 compared to their respective counterparts. The odds of death were significantly high for men and Black people.

STRENGTHS AND LIMITATIONS OF THIS STUDY

First multi-ethnic population-based study on COVID-19 in patients with hepato-pancreato-biliary group of diseases.

Systematic identification of the effect, or the lack of it, of individual demographic and clinical factors on the infection and mortality of COVID-19 in a large cohort of over 15 000 patients, robustly controlling for potential confounders in their evaluation.

Access to longitudinal data from linked primary and secondary care electronic health records, and use of rule-based phenotyping algorithms allowed for improved completeness and accuracy of the explored variables.

Some observed increased odds of SARS-CoV-2 infection and related death could be plausibly explained by unmeasured confounding.

The effects reported in the study could be influenced by the relatively smaller size of COVID-19 cases within this cohort.
Molecular characterisation of longitudinally collected circulating cell-free DNA in HPV+ve and HPV-ve oropharyngeal cancer
Authors: Thomson John P , Warlow Sophie J , Adamowicz Martyna , Thain Helen , Cuschieri Kate , Li Lucy Q , Conn Brendan , Hay Ashley , Nixon Iain J , Aitman Timothy J
Published: September 2020

Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing global health problem and is divided into two types dependent on association with human papillomavirus (HPV), with a more favourable prognosis in virus-associated tumours. Current methods of establishing viral aetiology, assessing response to therapy and clinical monitoring rest on tissue biopsy, clinical examination and post-treatment imaging. However, tissue biopsy is invasive and carries significant risk of morbidity, and post-treatment scans are frequently indeterminate. Analysis of cell-free DNA (cfDNA) from the circulation provides a minimally invasive method for detecting and monitoring cancer-derived DNA fragments, with the potential for enhancing clinical care. Through the longitudinal collection of 166 blood samples in 67 OPSCC patients we evaluate the utility of three cfDNA analysis methods: droplet digital PCR (ddPCR) and fragment size analysis in both HPV+ve and HPV-ve disease, and ultra-deep sequencing in patients with HPV-ve disease. We show that ddPCR analysis of cfDNA for five HPV types (16, 18, 31, 33 & 35) is strongly concordant with existing clinical assays (p16 immunohistochemistry (IHC) and quantitative PCR analysis of solid tumour tissue) and that cfDNA fragment size was reduced in OPSCC patients compared to healthy controls. Sequential ddPCR measurements of cfDNA HPV copy number showed a decrease to undetectable levels in all 30 HPV+ve patients in at least one of their post-treatment samples and a corresponding increase in cfDNA fragment size in patients who had a complete response to chemoradiotherapy. In two HPV+ve patients, clinical decision-making based on HPV ddPCR of cfDNA may have led to earlier detection of relapse in one patient or avoided surgical exploration in a second patient, which led to resection of tissue that did not harbour malignancy. In HPV-ve disease, ultra-deep sequencing identified tumour-derived somatic mutations of circulating cfDNA in genes such as TP53 and members of the ERBB family that are potential markers of therapeutic responsiveness and patient prognosis. Together our data suggest that analysis of circulating cfDNA can enhance current clinical strategies for assessing therapeutic response and disease monitoring in both HPV+ve and HPV-ve OPSCC.
The impact of timely cancer diagnosis on age disparities in colon cancer survival in New Zealand
Authors: Pilleron Sophie , Maringe Camille , Charvat Hadrien , Atkinson June , Morris Eva , Sarfati Diana
Published: September 2020

Objective

We described the role of patient-related and clinical factors on age disparities in colon cancer survival among patients aged 50-99 using New Zealand population-based cancer registry data linked to hospitalization data.

Design

We included new colon cancer cases diagnosed between 1 January 2006 and 31 July 2017, followed up to 31 December 2019. We linked these cases to hospitalisation data for the five years before the cancer diagnosis. We modelled the effect of age at diagnosis, sex, deprivation, comorbidity, and route to diagnosis on colon cancer survival by stage at diagnosis (localized, regional, distant, missing).

Results

Net survival decreased as the age at diagnosis increased, notably in advanced stages and missing stage. The excess mortality in older patients was minimal for localised cancers, maximal during the first six months for regional cancers, the first 18 months for distant cancers, and over the three years for missing stages. The age pattern of the excess mortality hazard varied according to sex for distant cancers, the route to diagnosis for regional and distant cancers, and comorbidity for cancer with missing stages.

Conclusion

The present population-based study shows that factors reflecting timeliness of cancer diagnosis most affected the difference in survival between middle-aged and older patients, probably by impacting treatment strategy. Because of the high risk of poor outcomes related to treatment in older patients, efforts made to improve earlier diagnosis in older patients are likely to help reduce age disparities in colon cancer survival in New Zealand.
Network for subclinical prognostication of COVID 19 Patients from data of thoracic roentgenogram: A feasible alternative screening technology
Authors: Bararia Akash , Ghosh Abhirup , Bose Chiranjit , Bhar Debarati
Published: September 2020

Background and Study Aim

COVID 19 is the terminology driving people’s life in the year 2020 without a supportive globally high mortality rate. Coronavirus lead pandemic is a new found disease with no gold standard diagnostic and therapeutic guideline across the globe. Amidst this scenario our aim is to develop a prediction model that makes mass screening easy on par with reducing strain on hospitals diagnostic facility and doctors alike. For this prediction model, a neural network based on Chest X-ray images has been developed. Alongside the aim is also to generate a case record form that would include prediction model result along with few other subclinical factors for generating disease identification. Once found positive then only it will proceed to RT-PCR for final validation. The objective was to provide a cheap alternative to RT-PCR for mass screening and to reduced burden on diagnostic facility by keeping RT-PCR only for final confirmation.

Methods

Datasets of chest X-ray images gathered from across the globe has been used to test and train the network after proper dataset curing and augmentation.

Results

The final neural network-based prediction model showed an accuracy of 81% with sensitivity of 82% and specificity of 90%. The AUC score obtained is 93.7%.

Discussion and Conclusion

The above results based on the existing datasets showcase our model capability to successfully distinguish patients based on Chest X-ray (a non-invasive tool) and along with the designed case record form it can significantly contribute in increasing hospitals monitoring and health care capability.
Geographical variation and factors associated with unsafe child stool disposal in Ethiopia: A spatial and multilevel analysis
Authors: Sahiledengle Biniyam , Teferu Zinash , Tekalegn Yohannes , Awoke Tadesse , Zenbaba Demisu , Bekele Kebebe , Tesemma Abdi , Seyoum Fikadu , Woldeyohannes Demelash
Published: September 2020

Background

Unsafe disposal of children’s stool makes children susceptible to fecal-oral diseases and children remain vulnerable till the stools of all children are disposed of safely. There is a paucity of data on spatial distribution and factors associated with unsafe child stool disposal in Ethiopia. Previous estimates, however, do not include information regarding individual and community-level factors associated with unsafe child stool disposal. Hence, the current study aimed (i) to explore the spatial distribution and (ii) to identify factors associated with unsafe child stool disposal in Ethiopia.

Methods

A secondary data analysis was conducted using the recent 2016 Ethiopian demographic and health survey data. A total of 4145 children aged 0–23 months with their mother were included in this analysis. The Getis-Ord spatial statistical tool was used to identify high and low hotspots areas of unsafe child stool disposal. The Bernoulli model was applied using Kilduff SaTScan version 9.6 software to identify significant spatial clusters. A multilevel binary logistic regression model was fitted to identify factors associated with unsafe child stool disposal.

Results

Unsafe child stool disposal was spatially clustered in Ethiopia (Moran’s Index = 0.211, p-value < 0.0001), and significant spatial SaTScan clusters of areas with a high rate of unsafe child stool disposal were detected. The most likely primary SaTScan cluster was detected in Tigray, Amhara, Afar (north), and Benishangul-Gumuz (north) regions (LLR: 41.62, p< 0.0001). Unsafe child stool disposal is more prevalent among households that had unimproved toilet facility (AOR = 1.54, 95%CI: 1.17-2.02), and those with high community poorer level (AOR: 1.74, 95%CI: 1.23-2.46). Higher prevalence of unsafe child stool disposal was also found in households with poor wealth quintiles. Children belong to agrarian regions (AOR: 0.62, 95%CI 0.42-0.91), children 6-11 months of age (AOR: 0.66, 95%CI: 0.52-0.83), 12-17 months of age (AOR: 0.68, 95%CI: 0.54-0.86), and 18-23 months of age (AOR: 0.58, 95%CI: 0.45-0.74) had lower odds of unsafe child stool disposal.

Conclusions

Unsafe child stool disposal was spatially clustered. Higher odds of unsafe child stool disposal were found in households with high community poverty level, poor, unimproved toilet facility, and with the youngest children. Hence, the health authorities could tailor effective child stool management programs to mitigate the inequalities identified in this study. It is also better to consider child stool management intervention in existing sanitation activities considering the identified factors.