bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregnancy outcomes following maternal treatment with rituximab prior to or during pregnancy: a case series
Authors: Perrotta Kirstie , Kiernan Elizabeth , Bandoli Gretchen , Manaster Rachel , Chambers Christina
Published: January 2021

Objective

Rituximab is a CD20-directed cytolytic antibody used for non-Hodgkin lymphoma, chronic lymphocytic leukaemia and RA, and off label for JIA, multiple sclerosis and lupus. Owing to concerns about infant B cell depletion, the manufacturer recommends avoidance of rituximab throughout pregnancy and for 12 months before conception. The aim of this study was to add to the limited data on pregnancy outcomes in women with exposure to rituximab.

Methods

Data were obtained from MotherToBaby Pregnancy Studies. Participants were enrolled prospectively into this observational study between 2007 and 2019. Pregnancy exposure and outcome data were collected from medical records, telephone interviews and dysmorphology examinations. The outcomes examined included spontaneous abortion, stillbirth, premature delivery, pregnancy complications, major and minor anomalies, small for gestational age, neonatal complications and serious infections.

Results

We classified 19 women with exposure to rituximab into three groups. Group A included three women who received rituximab during pregnancy. Group B included three women who received their last infusion before conception but had assumed pregnancy exposure owing to the long half-life of the drug. Group C included 13 women who used rituximab in the 2 years before pregnancy, with the last infusion given no sooner than five half-lives before conception. Three children had a major structural defect. Preterm delivery occurred in two pregnancies, and two infants were small for gestational age on birth weight. No cases of B cell depletion were reported.

Conclusion

No pattern of major structural anomalies or other adverse outcomes was reported in this case series.
Effect of silage source, physically effective neutral detergent fiber, and undigested neutral detergent fiber concentrations on performance and carcass characteristics of finishing steers
Authors: Pereira Murillo C S , Yang Wenzhu Z , Beauchemin Karen A , McAllister Tim A , Wood Katharine M , Penner Gregory B
Published: January 2021

This study was designed to evaluate the effect of silage source (barley vs. wheat silage) when harvested at two chop lengths (low vs. high physically effective neutral detergent fiber [peNDF]) and when barley silage was partially replaced with straw to increase the undigested neutral detergent fiber (uNDF) concentration on performance and carcass characteristics of finishing steers. Four hundred and fifty yearling commercial crossbred steers with an initial body weight (BW) of 432 ± 30.5 kg were allocated to 30 pens and fed diets containing 90% concentrate:10% forage for 123 d in a completely randomized block design with a 2 × 2 + 1 factorial arrangement. Treatments included 1) barley silage (BarS) with low peNDF (LpeNDF); 2) BarS with high peNDF (HpeNDF); 3) BarS with straw to yield a diet with LpeNDF + uNDF; 4) wheat silage (WhS) LpeNDF; and 5) WhS HpeNDF. There were no silage × peNDF interactions for dry matter intake (DMI), average daily gain (ADG), or gain to feed ratio (G:F), but cattle fed WhS LpeNDF had a lower (P < 0.01) proportion of yield grade 3 and a greater proportion in yield grade 2 carcasses than cattle fed BarS LpeNDF or HpeNDF and WhS HpeNDF. Cattle fed WhS LpeNDF had greater (P = 0.02) incidence of severe liver abscesses when compared with cattle fed BarS LpeNDF or HpeNDF and WhS HpeNDF. Cattle fed BarS consumed less (P < 0.01) uNDF as a percentage of BW, had increased (P = 0.02) ADG, heavier (P = 0.02) hot carcass weight, with greater (P = 0.01) back fat thickness, and (P < 0.01) incidence of minor liver abscesses when compared with cattle fed WhS. Feeding HpeNDF did not affect DMI, ADG, or G:F, but increased (P = 0.02) marbling score and reduced (P < 0.01) the proportion AA quality grade and increased (P < 0.01) those classified as AAA when compared with cattle fed LpeNDF. Cattle fed low uNDF had lesser (P < 0.01) uNDF intake as a percentage of BW, greater dressing percentage (P = 0.01), had a lower (P < 0.01) proportion of carcasses in yield grade 2, and a greater (P < 0.01) proportion of carcasses in yield grade 3 when compared with cattle fed high uNDF. Thus, silage source, peNDF, and uNDF content do not impact DMI or G:F when diets contain 10% forage, but BarS relative to WhS as well strategies increasing the peNDF concentration may increase ADG, HCW, back fat thickness, dressing percentage, marbling score, and carcasses classified as quality grade AAA. Future research is needed to evaluate the usefulness of peNDF and uNDF in rations for finishing cattle.
Bacterial and Fungal Microbiome Profiling in Chilhuacle Negro Chili (Capsicum annuum L.) Associated With Fruit Rot Disease
Authors: Fajardo-Rebollar Evelia , Estrada Karel , Grande Ricardo , Ek Ramos María Julissa , Vargas Gerardo Ruiz , Villegas-Torres Oscar Gabriel , Juárez A. M. , Sanchez-Flores Alejandro , Díaz-Camino Claudia
Published: January 2021

Chilhuacle negro chili (Capsicum annuum L.) is an ancient Mexican landrace that is deeply linked to the culinary heritage of the country. Because of the high profitability and uniqueness of this crop, the Universidad Autónoma del Estado de Morelos is exploring its production in controlled environments. In the crop cycles of 2018 to 2019, the production of chilhuacle negro plants was seriously affected by an unidentified pathogen causing fruit rot, which reduced its quality, yield, and market value. Therefore, the main objective of this work was to study and characterize the fruit microbiota, which could help reveal the causal agent of this disease. Using DNA metabarcoding coupled with Illumina and nanopore sequencing technologies, we collected and analyzed both healthy and infected chili fruit, along with greenhouse bioaerosols. We also explored the bacterial and fungal microbiota by using microbiological techniques to isolate some of the culturable bacterial and fungal species. Our results suggest that the seedborne fungus Alternaria alternata is activated during the maturation stage of chilhuacle negro fruit, triggering a microbiome imbalance, which may in turn enable the establishment of other opportunistic pathogenic fungi during fruit decay, such as Mucor sp. To our knowledge, this is the first study of the chilhuacle negro chili microbiome, which can shed some light on our understanding of one of the main diseases that affect this valuable crop.
Intramedullary Antibiotic Depot Does Not Preclude Successful Intramedullary Lengthening or Compression
Authors: Rivera Jessica C. , McClure Philip K. , Fragomen Austin T. , Mehta Samir , Rozbruch S. Robert , Conway Janet D.
Published: January 2021

The challenging problem of long bone infection and limb length difference cannot be addressed using only an antibiotic-coated nonmagnetic static nail. The combined use of resorbable calcium sulfate and magnetic lengthening nails offers a possible solution to this dilemma, as well as for infected nonunions that require compression. We present a combined technique to treat or prevent infection using femoral or tibial intramedullary antibiotic delivery with an absorbable calcium sulfate depot and concomitant internal lengthening or compression using a nail. Adequate débridement is required in cases of established infection and is a prerequisite for this technique.
Antimicrobial Activity of Ceftazidime-Avibactam Against Contemporary Pathogens From Urinary Tract Infections and Intra-abdominal Infections Collected From US Children During the 2016–2019 INFORM Surveillance Program
Authors: Lin Lynn-Yao , Riccobene Todd , Debabov Dmitri
Published: January 2021

Background:

Antibacterial activity of ceftazidime-avibactam (CAZ-AVI) was evaluated against bacterial isolates from children in the United States with a urinary tract infection (UTI) or intra-abdominal infection (IAI) during the 2016–2019 International Network for Optimal Resistance Monitoring program. Prevalence of isolates and susceptibility to CAZ-AVI in pediatric and adult patients were compared.

Methods:

Bacterial isolates were collected from children with a UTI or IAI at 70 US medical centers from 2016 to 2019. The antimicrobial activity of CAZ-AVI and comparator agents was tested by broth microdilution methods.

Results:

The most prevalent Enterobacterales pathogens in children with UTIs were Escherichia coli (62.5%), Klebsiella pneumoniae (12.1%) and Proteus mirabilis (6.2%). Minimum inhibitory concentration 90% values for CAZ-AVI against Enterobacterales (0.25 μg/mL) and Pseudomonas aeruginosa (4 μg/mL) were identical for children and adults. The most prevalent Enterobacterales pathogens in children with IAIs were E. coli (57.4%), K. pneumoniae (11.1%) and Enterobacter cloacae species complex (9.3%). All isolates of Enterobacterales from pediatric patients with UTI and IAI were susceptible to CAZ-AVI, including extended-spectrum β-lactamase phenotypes. Susceptibility of P. aeruginosa isolates to CAZ-AVI was 96.2% in children and 98.4% in adults with a UTI: for IAI it was 100% and 97.2%, respectively.

Conclusions:

Contemporary UTI and IAI pathogens collected from US children from 2016 to 2019 exhibited similar prevalence and susceptibilities as isolates collected from adult patients. CAZ-AVI exhibited potent activity against these pathogens.
Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and the Risk of SARS-CoV-2 Infection or Hospitalization With COVID-19 Disease: A Systematic Review and Meta-Analysis
Authors: Tleyjeh Imad M. , Bin Abdulhak Aref A. , Tlayjeh Haytham , Al-Mallah Mouaz H. , Sohail M. Rizwan , Hassett Leslie C. , Siller-Matula Jolanta M. , Kashour Tarek
Published: January 2021

Background:

SARS-CoV-2 infects its target cells via angiotensin converting enzyme 2 receptor, a membrane-bound protein found on the surface of many human cells. Treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptors blockers (ARB) has been shown to increase angiotensin converting enzyme 2 expression by up to 5-fold.

Areas of uncertainty:

These findings coupled with observations of the high prevalence and mortality among SARS-CoV-2-infected patients with underlying cardiovascular disease have led to a speculation that ACEIs/ARBs may predispose to higher risk of being infected with SARS-CoV-2. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and the risk of SARS-CoV-2 infection or hospitalization due to COVID-19 disease.

Data sources:

We searched Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Medrxiv.org preprint server until June 18, 2020.

Therapeutic advances:

Ten studies (6 cohorts and 4 case control) that enrolled a total of 23,892 patients and 853,369 controls were eligible for inclusion in our meta-analysis. One study was excluded from the analysis because of high risk of bias. Prior use of ACEIs was not associated with an increased risk of acquiring SARS-CoV-2 or hospitalization due to COVID-19 disease, odds ratio 0.98, 95% confidence interval (0.91–1.05), I2 = 15%. Similarly, prior use of ARBs was not associated with an increased risk of acquiring SARS-CoV-2, odds ratio 1.04, 95% confidence interval (0.98–1.10), I2 = 0%.

Conclusion:

Cumulative evidence suggests that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19 or hospitalization due to COVID-19 disease. Our results provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs because of fear of COVID-19.
Global bifurcation at isolated singular points of the Hadamard derivative
Authors: Stuart C. A.
Published: January 2021

Consider

F
∈
C
(

R

×
X
,
Y
)

such that
F
(
λ
, 0) = 0 for all

λ
∈

R

, where
X
and
Y
are Banach spaces. Bifurcation from the line

R

×
{
0
}

of trivial solutions is investigated in cases where
F
(
λ
, · ) need not be Fréchet differentiable at 0. The main results provide sufficient conditions for
μ
to be a bifurcation point and yield global information about the connected component of

{
(
λ
,
u
)
:
F
(
λ
,
u
)
=
0

 and 

u
≠
0
}
∪
{
(
μ
,
0
)
}

containing (
μ
, 0). Some necessary conditions for bifurcation are also formulated. The abstract results are used to treat several singular boundary value problems for which Fréchet differentiability is not available.

This article is part of the theme issue ‘Topological degree and fixed point theories in differential and difference equations’.
Non-local second-order boundary value problems with derivative-dependent nonlinearity
Authors: Webb J. R. L.
Published: January 2021

We prove the existence of multiple positive solutions of nonlinear second-order nonlocal boundary value problems with nonlinear term having derivative dependence. We allow the nonlinearity to grow quadratically with respect to derivatives. We obtain
a priori
bounds for norms of derivatives by using a recently obtained Gronwall-type inequality. Three examples illustrate some of the results.

This article is part of the theme issue ‘Topological degree and fixed point theories in differential and difference equations’.
High levels of plasminogen activator inhibitor-1, tissue plasminogen activator and fibrinogen in patients with severe COVID-19
Authors: Cabrera-Garcia David , Miltiades Andrea , Parsons Samantha , Elisman Katerina , Mansouri Mohammad Taghi , Wagener Gebhard , Harrison Neil L.
Published: January 2021

We measured plasma levels of fibrinogen, plasminogen, tissue plasminogen activator (t-PA) and plasminogen activation inhibitor 1 (PAI-1) in blood from 37 patients with severe coronavirus disease-19 (COVID-19) and 23 controls. PAI-1, t-PA and fibrinogen levels were significantly higher in the COVID-19 group. Increased levels of PAI-1 likely result in lower plasmin activity and hence decreased fibrinolysis. These observations provide a partial explanation for the fibrin- mediated increase in blood viscosity and hypercoagulability that has previously been observed in COVID-19. Our data suggest that t-PA administration may be problematic, but that other interventions designed to enhance fibrinolysis might prove useful in the treatment of the coagulopathy that is often associated with severe COVID-19.
AMELIE 3: Fully Automated Mendelian Patient Reanalysis at Under 1 Alert per Patient per Year
Authors: Birgmeier Johannes , Steinberg Ethan , Bodle Ethan E. , Deisseroth Cole A. , Jagadeesh Karthik A. , Kohler Jennefer N. , Bonner Devon , Marwaha Shruti , Martinez-Agosto Julian A. , Nelson Stan , Palmer Christina G. , Cogan Joy D. , Hamid Rizwan , Stoler Joan M. , Krier Joel B. , Rosenfeld Jill A. , Moretti Paolo , Adams David R. , Shashi Vandana , Worthey Elizabeth A. , Eng Christine M. , Ashley Euan A. , Wheeler Matthew T. ,   Undiagnosed Diseases Network, Stenson Peter D. , Cooper David N. , Bernstein Jonathan A. , Bejerano Gill
Published: January 2021

Background

Many thousands of patients with a suspected Mendelian disease have their exomes/genomes sequenced every year, but only about 30% receive a definitive diagnosis. Since a novel Mendelian gene-disease association is published on average every business day, thousands of undiagnosed patient cases could receive a diagnosis each year if their genomes were regularly compared to the latest literature. With millions of genomes expected to be sequenced for rare disease analysis by 2025, and considering the current publication rate of 1.1 million new articles per annum in PubMed, manually reanalyzing the growing cases of undiagnosed patients is not sustainable.

Methods

We describe a fully automated reanalysis framework for patients with suspected, but undiagnosed, Mendelian disorders. The presented framework was tested by automatically parsing all ∼100,000 newly published peer reviewed papers every month and matching them on genotype and phenotype with all stored undiagnosed patients. If a new article contains a possible diagnosis for an undiagnosed patient, the system provides notification. We test the accuracy of the automatic reanalysis system on 110 patients, including 61 with available trio data.

Results

Even when trained only on older data, our system identifies 80% of reanalysis diagnoses, while sending only 0.5-1 alerts per patient per year, a 100-1,000-fold efficiency gain over manual literature surveillance of equivalent yield.

Conclusion

We show that automatic reanalysis of patients with suspected Mendelian disease is feasible and has the potential to greatly streamline diagnosis. Our system is not intended to replace clinical judgment. Rather, clinical diagnostic services could greatly benefit from a modest re-allocation of time from manual literature exploration to review of automated reanalysis alerts. Our system additionally supports a new paradigm for medical IT systems: proactive, continuously learning and consequently able to autonomously identify valuable insights as they emerge in digital health records. We have launched automated patient reanalysis, trained on the latest data, with user accounts and daily literature updates at https://AMELIE.stanford.edu.
One Shot Model For The Prediction of COVID-19 and Lesions Segmentation In Chest CT Scans Through The Affinity Among Lesion Mask Features
Authors: Ter-Sarkisov Aram
Published: January 2021

We introduce a model that segments lesions and predicts COVID-19 from chest CT scans through the derivation of an affinity matrix between lesion masks. The novelty of the methodology is based on the computation of the affinity between the lesion masks’ features extracted from the image. First, a batch of vectorized lesion masks is constructed. Then, the model learns the parameters of the affinity matrix that captures the relationship between features in each vector. Finally, the affinity is expressed as a single vector of pre-defined length. Without any complicated data manipulation, class balancing tricks, and using only a fraction of the training data, we achieve a 91.74% COVID-19 sensitivity, 85.35% common pneumonia sensitivity, 97.26% true negative rate and 91.94% F1-score. Ablation studies show that the method can quickly generalize to new datasets. All source code, models and results are publicly available on https://github.com/AlexTS1980/COVID-Affinity-Model.
Respiratory and non-respiratory manifestations in children admitted with COVID 19 in Rio de Janeiro city, Brazil
Authors: Araujo da Silva AR , Fonseca CGB , Miranda JLPS , Travassos BV , Baião CR , Silva KD , dos Santos LBAE , de Britto MMR , Cerqueira PALS , Pereira SNB , Rios RBJ , Vieira CS , Leal IA , Martins NC , de Carvalho LMAC , Pereira AB , Teixeira CH
Published: January 2021

Introduction

COVID 19 is still a challenge in pediatrics due to variety of symptoms and different presentations

Aim

To describe clinical, laboratorial and treatment of confirmed COVID-19 pediatric admitted in hospitals.

Methods

A retrospective study was conducted in children (0-18 years), admitted between March and November 15, 2020, with confirmed COVID-19 by reverse transcription polymerase chain reaction or serological tests. Clinical data about symptoms, laboratorial exams and treatments were analysed. Patients were evaluated according predominant (PRS) or non-predominant respiratory symptoms (non-PRS)

Results

Sixty-four patients were evaluated, being the median age 5.6 years. Forty-seven (73.4%) children were admitted with PRS and 17 (26.4%) with non-PRS. The main symptoms in the PRS group were fever in 74.5% of children and cough in 66%; and fever in 76.5% and edema/cavitary effusion in 29.4% in the non-PRS group. The median of C-reactive protein (in mg/dl) was 2.5 in the PRS group and 6.1 in the non-PRS group. Antibiotics were used in 85.1% of the PRS group and 94.1% of non-group. Comorbidity was present in 30/47 (63.8%) of PRS group and 8/17 (47.1%) of non-PRS group (p=0.22). Length of stay until 7 days in patients with comorbidity was present in 27/64 (42.1%) and more than 7 days in 11/64 (17.1%) (p= 0.2)

Conclusion

Non-PRS represented more than one quarter of admitted patients. Fever was the main symptom detected, elevated CRP was frequent and antibiotics were commonly prescribed. Comorbidity was found in both groups and his presence was not associated with a longer length of stay.
Antemortem vs. postmortem histopathological and ultrastructural findings in paired transbronchial biopsies and lung autopsy samples from three patients with confirmed SARS-CoV-2 infection
Authors: Gagiannis D , Umathum VG , Bloch W , Rother C , Stahl M , Witte HM , Djudjaj S , Boor P , Steinestel K
Published: January 2021

Background

Acute respiratory distress syndrome (ARDS) is the major cause of death in coronavirus disease 2019 (COVID-19). Multiple autopsy-based reports of COVID-19 lung pathology describe diffuse alveolar damage (DAD), organizing pneumonia (OP) and fibrotic change, but data on early pathological changes as well as during progression of the disease are rare.

Research question

Comparison of histopathological and ultrastructural findings in paired transbronchial biopsies (TBBs) and autopsy material from three patients with confirmed SARS-CoV-2-infection.

Methods

We prospectively enrolled 3 patients with confirmed SARS-CoV-2 infection. Full clinical evaluation was performed including high-resolution computed tomography (HR-CT). We took TBBs at different time points during the disease and autopsy tissue samples after the patients’ death.

Results

SARS-CoV-2 was detected by RT-PCR and/or FISH in all TBBs. Lung histology revealed pneumocyte hyperplasia and capillary congestion in one patient who died short after hospital admission with detectable virus in 1/2 autopsy samples from the lung. SARS-CoV-2 was detected in 2/2 autopsy samples from a patient with a fulminant course of the disease and very short latency between biopsy and autopsy, both showing widespread DAD. In a third patient with a prolonged course, i.e. five weeks of ICU treatment with ECMO, autopsy samples showed extensive interstitial fibrosis without detectable virus by RT-PCR and/or FISH.

Interpretation

We report the course of COVID-19 in paired TBB and autopsy samples from three patients at an early stage, in rapidly progressive and in a prolonged disease course. Our findings illustrate vascular, organizing and fibrotic patterns of COVID-19-induced lung injury and suggest an early spread of SARS-CoV-2 from the upper airways to the lung periphery with diminishing viral load during disease.
Does the Pareto Principle describe parasite counts in humans? The case of hookworm in pregnant women
Authors: Orobio Yenifer , Alexander Neal
Published: January 2021

The Pareto Principle (PP) — that 80% of an attribute are found in 20% of individuals — is one way to characterize heterogeneity in infectious diseases. An alternative is the dispersion parameter (k) of the negative binomial distribution (NBD). The NBD has two parameters, while the PP is a single property which may hold for any distribution family. The objectives of the current work are: a) to obtain a relation between the PP and NBD, i.e. to specify which combinations of NBD parameters comply with the PP; b) for hookworm, a soil-transmitted intestinal parasite of humans, to identify whether the PP or the NBD is a more parsimonious description of heterogeneity of infection load. For objective a), an empirical relation is found in the form of a saw-toothed line on a plot ofkagainst the mean, reaching an asymptote of approximately 0.24. For objective b), we estimatekand the mean from nine studies from a systematic review of hookworm in pregnant women. Seven studies had higher heterogeneity than the PP, ranging from 83:20 to 100:20: we call these super-Pareto. One study was sub-Pareto (74:20), and one was Pareto (80:20). This suggests that at least two parameters, as supplied by the NBD, are necessary to describe the heterogeneity of hookworm. The probability of reaching a target reduction in prevalence is less when there is greater aggregation, which suggests that estimating aggregation via a subsample could be worthwhile, in order to set a target coverage threshold before starting mass drug administration.
Gut Microbiome Predicts Clinically Important Improvement in Patients with Rheumatoid Arthritis
Authors: Gupta Vinod K. , Cunningham Kevin Y. , Bakshi Utpal , Hur Benjamin , Huang Harvey , Warrington Kenneth J. , Taneja Veena , Myasoedova Elena , Davis John M. , Sung Jaeyun
Published: January 2021

Background

Rapid advances in the past decade have shown that dysbiosis of the gut microbiome is a key hallmark of rheumatoid arthritis (RA). Yet, the relationship between gut microbiome and clinical improvement in RA disease activity remains unclear. In this study, we explored the gut microbiome of patients with RA to identify features that are associated with, as well as predictive of, minimum clinically important improvement (MCII) in disease activity.

Methods

Whole metagenome shotgun sequencing was performed on 64 stool samples, which were collected from 32 patients with RA at two separate time-points. The Clinical Disease Activity Index (CDAI) of each patient was measured at both time-points to assess achievement of MCII; depending on this clinical status, patients were distinguished into two groups. Multiple linear regression models were used to identify microbial taxa and biochemical pathways associated with MCII while controlling for potentially confounding factors. Lastly, a deep-learning neural network was trained upon gut microbiome, clinical, and demographic data at baseline to classify patients according to MCII status, thereby enabling the prediction of whether a patient will achieve MCII at follow-up.

Results

We determined that MCII status can explain a significant proportion of the overall compositional variance in the gut microbiome (R2 = 3.8%, P = 0.005, PERMANOVA). Additionally, by looking at patients’ baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed MCII and those who did not. Taxonomic features include alpha- and beta-diversity measures, as well as several microbial taxa, such as Coprococcus, Bilophila sp. 4_1_30, and Ruminococcus sp. Functional profiling identified thirteen biochemical pathways, most of which were involved in the biosynthesis of L-arginine and L-methionine, to be differentially abundant between the MCII patient groups. In addition to these observations at baseline, we found microbiome features that vary differently in fold-change (from baseline to follow-up) between the two patient groups. These results could suggest that, depending on the clinical course, gut microbiomes not only start at different ecological states, but also are on separate trajectories. Finally, the neural network proved to be highly effective in predicting which patient will achieve MCII (balanced accuracy = 90.0%), demonstrating potential clinical utility of gut microbiome profiles.

Conclusions

Our findings confirm the presence of taxonomic and functional signatures of the gut microbiome associated with MCII in RA patients. Ultimately, the gut microbiome may aid in the development of non-invasive tools for predicting future prognosis in RA.

Trial registration

N/A
A MULTI-MINERAL INTERVENTION TO MODULATE COLONIC MUCOSAL PROTEIN PROFILE: Results from a 90-day trial in healthy human subjects
Authors: Aslam Muhammad N. , McClintock Shannon D. , Jawad-Makki Mohamed Ali H. , Knuver Karsten , Ahmad Haris M. , Basrur Venkatesha , Bergin Ingrid L. , Zick Suzanna M. , Sen Ananda , Turgeon D. Kim , Varani James
Published: January 2021

The overall goal of this study was to determine if Aquamin®, a calcium- and magnesium-rich natural product, would alter the expression of proteins involved in growth-regulation, differentiation and barrier formation in the colon. Thirty healthy human subjects were enrolled in a three-arm, 90-day interventional trial in which Aquamin®(provided daily to deliver 800-mg of calcium per day) was compared to calcium alone and placebo. Before and after the 90-day interventional period, colonic biopsies were obtained. Biopsies were evaluated by immunohistology for expression of Ki67 (a proliferation marker) and for CK20 and p21 (differentiation markers). Tandem mass tag-mass spectrometry-based detection was used to assess levels of multiple proteins. As compared to placebo or calcium, Aquamin®reduced the level of Ki67 expression (20%). Neither intervention altered CK20 expression, while a trend toward increased p21 was observed with calcium and Aquamin®(117% and 99% respectively). In the proteomic screen, Aquamin®treatment resulted in many more proteins being upregulated or downregulated (1.5 fold-change with ≤2% false-discovery rate) than placebo. Included among the upregulated proteins were cytokeratins, cell-cell adhesion molecules and components of the basement membrane. Many of the downregulated proteins were those involved in proliferation and nucleic acid metabolism. Calcium alone also altered the expression of many of the same proteins but not to the same extent as Aquamin®. We conclude that daily Aquamin®ingestion alters protein expression profile in the colon that could be beneficial to colonic health. These data warrant additional studies with a larger sample size to validate these findings.

Prevention Relevance

A multi-mineral approach reduced proliferation and induced differentiation inex vivosettings and has been shown to decrease colon polyp incidence in mouse (polyp-prevention) studies. The findings from a 90-day trial in human subjects (presented here) demonstrated improved biomarker-modulation efficacy, warranting to conduct the polyp-prevention trial in at-risk human subjects.
SANS serif: alignment-free, whole-genome based phylogenetic reconstruction
Authors: Rempel Andreas , Wittler Roland
Published: January 2021

SANS serif is a novel software for alignment-free, whole-genome based phylogeny estimation that follows a pangenomic approach to efficiently calculate a set of splits in a phylogenetic tree or network.

Availability and Implementation

Implemented in C++ and supported on Linux, MacOS, and Windows. The source code is freely available for download athttps://gitlab.ub.uni-bielefeld.de/gi/sans.

Contact

andreas.rempel@uni-bielefeld.de
Cellsnp-lite: an efficient tool for genotyping single cells
Authors: Huang Xianjie , Huang Yuanhua
Published: January 2021

Single-cell sequencing is an increasingly used technology and has promising applications in basic research and clinical translations. However, genotyping methods developed for bulk sequencing data have not been well adapted for single-cell data, in terms of both computational parallelization and simplified user interface. Here we introduce a software, cellsnp-lite, implemented in C/C++ and based on well supported package htslib, for genotyping in single-cell sequencing data for both droplet and well based platforms. On various experimental data sets, it shows substantial improvement in computational speed and memory efficiency with retaining highly concordant results compared to existing methods. Cellsnp-lite therefore lightens the genetic analysis for increasingly large single-cell data.

Availability

The source code is freely available athttps://github.com/single-cell-genetics/cellsnp-lite.

Contact

yuanhua@hku.hk
Distribution modeling ofLantana camaraand identification of hotspot for future management of the species in the lower Shivalik region of Uttarakhand, India
Authors: Mondal Tamali , Bhatt Dinesh , Ramesh K.
Published: January 2021

Invasive alien species are one of the most significant threats to biodiversity of the earth ecosystem. Spatial modeling has played a vital role in predicting and mapping the suitable areas of the species habitat for management implementation.Lantana camarais one of the ten worst invasive weed enlisted by IUCN., and has its distribution in more than 154000 sq. km area in India. We predicted the distribution ofLantana camarausing Ecological Niche Modeling (ENM) in MaxEnt software for Rajaji- Corbett landscape in the lower Shivalik region of the state of Uttarakhand, India. The predicted area for the invasion was classified into four categories high, good, medium, and low potential areas. The distribution hotspots were identified using Getis Ord G* method in ArcGIS 10.5 by calculating plot-wise species occurrence. Major hotspot areas under threat of high infestation are Dholkhand, Gohri, Ramgarh, Motichur, and Chilla from Rajaji Tiger Reserve, Palain, Mandal and Maidavan from Kalagarh Tiger Reserve and Bijrani, Dheela, Dhikala, Jhirna and Kalagarh from Corbett Tiger Reserve. This study provides a current status of the invasive species in the landscape with identified areas that need immediate actions to control the spread of the species. The study results can help the policymakers and stakeholders build an efficient and strategically weed management plan.
Identification of Common Molecular Signatures Shared between Alzheimer’s and Parkinson’s Diseases and Therapeutic Agents Exploration: An Integrated Genomics Approach
Authors: Faruqui Nairita Ahsan , Prium Durdana Hossain , Mowna Sadrina Afrin , Rahaman Tanjim Ishraq , Dutta Arundhati Roy , Akter Mst. Farjana
Published: January 2021

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two most prevalent age-related dementias that severely affect a large number of elderly people around the globe. Poor understanding of pathogenesis of these neurological diseases imposes challenge to discover therapeutic measures and effective diagnosis methods. In this study, a network-based approach was utilized to identify potential common molecular signatures and therapeutic agents for AD and PD. Protein-protein interaction analysis revealed NCK1, UBC, CDH1, CDC20, ACTB, PSMA7, PRPF8, RPL7, XRCC6 and HSP90AB1 as the best proteome signatures. Different regulatory transcriptional signatures i.e., YY1, NFKB1, BRCA1, TP53, GATA2, SREBF2, E2F1, FOXC1, RELA and NFIC and post-transcriptional signatures i.e., hsa-mir-186-5p, hsamir-92a-3p, hsa-mir-615-3p, hsa-let-7c-5p, hsa-mir-100-5p, hsa-mir-93-3p, hsa-mir-5681a, hsamir-484, hsa-mir-193b-3p and hsa-mir-16p-5p were identified from other interaction network. Drug-gene interaction study revealed possible therapeutic agents which may reverse the AD and PD condition. The scientific approach of this study should contribute to identify potential biomarkers, drug targets and therapeutic agents against AD and PD which should in turn advance the present efforts of scientists to secure effective diagnosis and therapeutic options. However, furtherin vivoandin vitroexperiments might be required to validate the outcomes of this study.
Machine Learning to Summarize and Provide Context for Sleep and Eating Schedules
Authors: Chen Tianyi , Chen Yiwen , Gao Jingyi , Gao Peiheng , Moon Jeong Hyun , Ren Jingyi , Zhu Ranran , Song Shanshan , Clark Jeanne M. , Bennett Wendy , Lehman Harold , Budavari Tamas , Woolf Thomas B.
Published: January 2021

The relative timing of sleep and of eating within the circadian day is important for human health. Despite much data on sleep, and a growing data set for eating, there remains a need for an interpretative framework for the understanding of this data for health decisions. This study provides a new statistical and machine learning analysis of more than 500 participants in the Daily24 project. From their data, and the analysis, we propose a framework for determining the classification of participants into different chronotypes and with that the ability to realize the potential impact of daily circadian habits on health. We propose that our resulting distribution curves could be used, similar to NHANES (National Health and Nutrition Examination Survey) data for pediatric growth, as a measure for circadian misalignment and used to help guide re-entrainment schedules.

Author summary

Daily habits can be positive, negative or neutral for human health. Generally sleep and eating schedules are assumed without thought for their potential to help or interfere with health. In this study we propose a framework, based on data from more than 500 participants, for evaluating the relative timing of meals and sleep schedules. This evaluation, similar to pediatric growth charts, can guide clinical suggestions for those at the extremes, while helping others to realize that they are unusual relative to the population average
Mechanistic Insight from Full Quantum Mechanical Modeling: Laccase as a Detoxifier of Aflatoxins
Authors: Zaccaria Marco , Dawson William , Kish Darius Russell , Reverberi Massimo , di Patti Maria Carmela Bonaccorsi , Domin Marek , Cristiglio Viviana , Dellafiora Luca , Gabel Frank , Nakajima Takahito , Genovese Luigi , Momeni Babak
Published: January 2021

We demonstrate a path towards full Quantum Mechanics (QM) characterization of enzymatic activity. As a case-study, we investigate the detoxification of aflatoxin, a carcinogenic food contaminant, by laccase, a versatile oxidase capable of—but not efficient for—degrading aflatoxin. We use a combination of quantitative experimentation and QM modeling to show that low enzymatic steric affinity for aflatoxin is the main bottleneck, rather that the oxidative activity of laccase. To identify the structural elements responsible for low reaction rates, we perform a density functional theory (DFT) based modeling of both the substrate and the enzyme in a full QM simulation of more than 7,000 atoms. Thanks to our approach we point to amino acid residues that determine the affinity of laccase for aflatoxin. We show that these residues are substrate-dependent, making a full QM approach necessary for enzyme optimization. Altogether, we establish a roadmap for rational enzyme engineering applicable beyond our case study.
Predicting the Yields of Species Occupying a Single Trophic Level with Incomplete Information: Two Approximations Based on the Lotka-Volterra Generalized Equations
Authors: Fort Hugo
Published: January 2021

The linear Lotka-Volterra generalized equations (LLVGE) serve for describing the dynamics of communities of species connected by negative as well as positive interspecific interactions.

Here we particularize these LLVGE to the case of a single trophic level community withS>2 species, either artificial or natural. In this case, by estimating the LLVGE parameters from the yields in monoculture and biculture experiments, the LLVGE are able to produce quite accurate predictions for species yields.

However, a common situation we face is that we don’t know all the parameters appearing in the LLVGE. Indeed, for large values ofS, only a fraction of the experiments necessary for estimating the model parameters is commonly carried out.

We then analyze which quantitative predictions are possible with an incomplete knowledge of the parameters. We discuss two approximations that allow using these LLVGE as a quantitative tool. First, when we only know a fraction of the model parameters, the mean field approximation allows making predictions on aggregate or average quantities. Second, for cases in which all the interaction parameters involving a particular species are available, we have the focal species approximation for predicting the yield of this focal species.
Identification of Cognitive Impairment in Cardiovascular Rehabilitation: A Cross-Sectional Study Protocol
Authors: Jamali Qutub , Karim Salman , Beg Mirza Najiullah , Raja Muhammad Shoaib , Solanki Kalpesh , Oraegbunam Chukwuma
Published: January 2021

Introduction

Cardiac Rehabilitation is a multidisciplinary intervention for people after an adverse cardiac event to improve their physical, psychological and social functioning. The risk factors of cardiac disease and dementia are similar. This cross sectional study aims to determine whether adding memory assessment to a cardiac rehabilitation program would improve early detection of cognitive impairment.

Methods and Analysis

Participants will undergo cognitive assessment by using Addenbrooke’s Cognitive Examination (ACE-III). The data obtained will be divided into: - 1- Participants who had a history of memory problems before and after the adverse cardiac event. 2-Participants with no history of memory problems before and currently presents with cognitive impairment. 3-Participants with no memory problems before and after the adverse cardiac event.

Ethics and dissemination

Study ethical approval has been granted by Sheffield Research Ethics Committee (reference 20/YH/0146) and the NHS Health Research Authority (project reference 273763).
LocusZoom.js: Interactive and embeddable visualization of genetic association study results
Authors: Boughton Andrew P. , Welch Ryan P. , Flickinger Matthew , VandeHaar Peter , Taliun Daniel , Abecasis Gonçalo R. , Boehnke Michael
Published: January 2021

LocusZoom.js is a JavaScript library for creating interactive web-based visualizations of genetic association study results. It can display one or more traits in the context of relevant biological data (such as gene models and other genomic annotation), and allows interactive refinement of analysis models (by selecting linkage disequilibrium reference panels, identifying sets of likely causal variants, or comparisons to the GWAS catalog). It can be embedded in web pages to enable data sharing and exploration. Views can be customized and extended to display other data types such as phenome-wide association study (PheWAS) results, chromatin co-accessibility, or eQTL measurements. A new web upload service harmonizes datasets, adds annotations, and makes it easy to explore user-provided result sets.

Availability

LocusZoom.js is open-source software under a permissive MIT license. Code and documentation are available at:https://github.com/statgen/locuszoom/. Installable packages are also distributed via NPM. Additional features are provided as standalone libraries to promote reuse. Use with your own GWAS results athttps://my.locuszoom.org/.

Contact

locuszoom@googlegroups.com
Moment-based approximations for the Wright-Fisher model of population dynamics under natural selection at two linked loci
Authors: He Zhangyi , Lyu Wenyang , Beaumont Mark , Yu Feng
Published: January 2021

Properly modelling genetic recombination and local linkage has been shown to bring significant improvement to the inference of natural selection from time series data of allele frequencies under a Wright-Fisher model. Existing approaches that can account for genetic recombination and local linkage are built on either the diffusion approximation or a moment-based approximation of the Wright-Fisher model. However, methods based on the diffusion approximation are likely to require much higher computational cost, whereas moment-based approximations may suffer from the distribution support issue: for example, the normal approximation can seriously affect computational accuracy. In the present work, we introduce two novel moment-based approximations of the Wright-Fisher model on a pair of linked loci, both subject to natural selection. Our key innovation is to extend existing methods to account for both the mean and (co)variance of the two-locus Wright-Fisher model with selection. We devise two approximation schemes, using a logistic normal distribution and a hierarchical beta distribution, respectively, by matching the first two moments of the Wright-Fisher model and the approximating model. As compared with the diffusion approximation, our approximations enable the approximate computation of the transition probabilities of the Wright-Fisher model at a far smaller computational cost. We can also avoid the distribution support issue found in the normal approximation.
Algorithm optimization for weighted gene co-expression network analysis: accelerating the calculation of Topology Overlap Matrices with OpenMP and SQLite
Authors: Shuai Min , Chen Xin
Published: January 2021

Motivation

Weighted gene co-expression network analysis (WGCNA) is an R package that can search highly related gene modules. The most time-consuming step of the whole analysis is to calculate the Topological Overlap Matrix (TOM) from the Adjacency Matrix in a single thread. This study changes it to multithreading.

Results

This paper uses SQLite for multi-threaded data transfer between R and C++, uses OpenMP to enable multi-threading and calculates the TOM via an adjacency matrix on a Shared-memory MultiProcessor (SMP) system, where the calculation time decreases as the number of physical CPU cores increases.

Availability and implementation

The source code is available athttps://github.com/do-somethings-haha/fast_calculate_TOM_of_WGCNA

Contact

chenxin@cdutcm.edu.cn
Structure-function investigation of a new VUI-202012/01 SARS-CoV-2 variant
Authors: Singh Jasdeep , Ehtesham Nasreen Z. , Rahman Syed Asad , Hasnain Seyed E.
Published: January 2021

The SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus) has accumulated multiple mutations during its global circulation. Recently, a new strain of SARS-CoV-2 (VUI 202012/01) had been identified leading to sudden spike in COVID-19 cases in South-East England. The strain has accumulated 23 mutations which have been linked to its immune evasion and higher transmission capabilities. Here, we have highlighted structural-function impact of crucial mutations occurring in spike (S), ORF8 and nucleocapsid (N) protein of SARS-CoV-2. Some of these mutations might confer higher fitness to SARS-CoV-2.

Since initial outbreak of COVID-19 in Wuhan city of central China, its causative agent; SARS-CoV-2 virus has claimed more than 1.7 million lives out of 77 million populations and still counting. As a result of global research efforts involving public-private-partnerships, more than 0.2 million complete genome sequences have been made available through Global Initiative on Sharing All Influenza Data (GISAID). Similar to previously characterized coronaviruses (CoVs), the positive-sense single-stranded RNA SARS-CoV-2 genome codes for ORF1ab non-structural proteins (nsp(s)) followed by ten or more structural/nsps [1, 2]. The structural proteins include crucial spike (S), nucleocapsid (N), membrane (M), and envelope (E) proteins. The S protein mediates initial contacts with human hosts while the E and M proteins function in viral assembly and budding. In recent reports on evolution of SARS-CoV-2, three lineage defining non-synonymous mutations; namely D614G in S protein (Clade G), G251V in ORF3a (Clade V) and L84S in ORF 8 (Clade S) were observed [2–4]. The latest pioneering works by Plante et al and Hou et al have shown that compared to ancestral strain, the ubiquitous D614G variant (clade G) of SARS-CoV-2 exhibits efficient replication in upper respiratory tract epithelial cells and transmission, thereby conferring higher fitness [5, 6]. As per latest WHO reports on COVID-19, a new strain referred as SARS-CoV-2 VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01) had been identified as a part of virological and epidemiological analysis, due to sudden rise in COVID-19 detected cases in South-East England [7]. Preliminary reports from UK suggested higher transmissibility (increase by 40-70%) of this strain, escalating Ro (basic reproduction number) of virus to 1.5-1.7 [7, 8]. This apparent fast spreading variant inculcates 23 mutations; 13 non-synonymous, 6 synonymous and 4 amino acid deletions [7]. In the current scenario, where immunization programs have already commenced in nations highly affected by COVID-19, advent of this new strain variant has raised concerns worldwide on its possible role in disease severity and antibody responses. The mutations also could also have significant impact on diagnostic assays owing to S gene target failures.