bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch2 complements Notch1 to mediate inductive signaling that initiates early T cell development
Authors: Romero-Wolf Maile , Shin Boyoung , Zhou Wen , Koizumi Maria , Rothenberg Ellen V. , Hosokawa Hiroyuki
Published: August 2020

Notch signaling is the dominant intercellular signaling input during the earliest stages of T cell development in the thymus. Although Notch1 is known to be indispensable, we show that it does not mediate all Notch signaling in precommitment stages: Notch2 initially works in parallel to promote early murine T cell development and antagonize other fates. Notch-regulated target genes before and after T lineage commitment change dynamically, and we show that this partially reflects shifts in genome-wide DNA binding by RBPJ, the transcription factor activated by complex formation with the Notch intracellular domain. Although Notch signaling and transcription factor PU.1 can activate some common targets in precommitment T progenitors, Notch signaling and PU.1 activity have functionally antagonistic effects on multiple targets, delineating separation of pro-T cells from alternative PU.1-dependent fates. These results define a distinct mechanism of Notch signal response that distinguishes the initial stages of murine T cell development.
Effects of annealing temperature on the structure, morphology, and photocatalytic properties of SnO2/rGO nanocomposites
Authors: Tuan Pham Van , Hieu Le Trung , Hoang Chu Manh , Tuong Hoang Ba , Tan Vu Thi , Hoa Tran Thi Quynh , Sang Nguyen Xuan , Khiem Tran Ngoc
Published: August 2020

Water pollution abatement is a problem in today’s society that requires urgent attention. Moreover, photocatalysts are an effective method to treat environmental pollution, and SnO2/reduced graphene oxide composite photocatalysts have been extensively studied in recent years. The synthesis parameters for these photocatalysts significantly affect their morphologies, structures, and properties. In this study, we investigated the effects of annealing temperatures on the properties of SnO2/reduced graphene oxide nanocomposites, which were hydrothermally fabricated at 180 °C for 24 h and annealed at 200 °C–800 °C. The structural characteristics of the fabricated nanocomposites were studied via x-ray diffraction, field emission scanning electron microscopy, and Raman scattering analyses. The observed results indicated that increasing the annealing temperature from 200 °C to 800 °C increased the average SnO2nanoparticle size from 4.60 nm to 9.27 nm; in addition, the Raman scattering peaks of the SnO2increased, and those of the reduced graphene oxide significantly decreased as the annealing temperature was increased. Furthermore, the specific surface area of the samples decreased due to the increase in calcination temperature. The amount of reduced graphene oxide content in all the samples was measured using thermo-gravimetric analysis. The optical properties of the samples were studied using ltraviolet–visible absorption spectra, and their photocatalytic activity was evaluated by decomposing methylene blue under visible light using the samples as catalysts. In particular, the photocatalytic properties of nanocomposites decreased significantly with increasing annealing temperature. Among the samples, the photocatalytic activity of that annealed at 200 °C is most satisfactory as it has the smallest particle size and the largest specific surface area. The results of our research could facilitate the production of efficient catalysts with suitable properties.
Inverse design of light–matter interactions in macroscopic QED
Authors: Bennett Robert , Buhmann Stefan Yoshi
Published: August 2020

Inverse design represents a paradigm shift in the development of nanophotonic devices, where optimal geometries and materials are discovered by an algorithm rather than symmetry considerations or intuition. Here we present a very general formulation of inverse design that is applicable to atomic interactions in external environments, and derive from this some explicit formulae for optimisation of spontaneous decay rates, Casimir–Polder forces and resonant energy transfer. Using Purcell enhancement of the latter as a simple example, we employ finite-difference time-domain techniques in a proof-of-principle demonstration of our formula, finding enhancement of the rate many orders of magnitude larger than a selection of traditional designs.
Visible stripe phases in spin–orbital-angular-momentum coupled Bose–Einstein condensates
Authors: Chiu N-C , Kawaguchi Y , Yip S-K , Lin Y-J
Published: August 2020

Recently, stripe phases in spin–orbit coupled Bose–Einstein condensates (BECs) have attracted much attention since they are identified as supersolid phases. In this paper, we exploit experimentally reachable parameters and show that annular stripe phases with large stripe spacing and high stripe contrast can be achieved in spin–orbital-angular-momentum coupled (SOAMC) BECs. In addition to using Gross–Pitaevskii numerical simulations, we develop a variational ansatz that captures the essential interaction effects to first order, which are not present in the ansatz employed in previous literature. Our work should open the possibility towards directly observing stripe phases in SOAMC BECs in experiments.
Massless limit of transport theory for massive Fermions *
Authors: Guo Xingyu
Published: August 2020

We studied the m = 0 limit of different components of Wigner functions for massive fermions. Comparing with the chiral kinetic theory, we separated the vanishing and non-vanishing parts of vector and axial-vector components, up to the first order of

. Then, we discussed the possible physical meaning of the vanishing and non-vanishing parts and their different behaviors at thermal equilibrium.
A compact analytical approximation for a light sterile neutrino oscillation in matter *
Authors: Yue Bao-Biao , Li Wei , Ling Jia-Jie , Xu Fan-Rong
Published: August 2020

The existence of light sterile neutrinos is a long-standing question in particle physics. Several experimental “anomalies” might be explained by introducing eV mass scaled light sterile neutrinos. Many experiments are actively searching for such light sterile neutrinos through neutrino oscillation. For long baseline experiments, the matter effect should be treated carefully for precise calculation of the neutrino oscillation probabilities. However, this is usually time-consuming or analytically complex. In this manuscript, we adopt a Jacobi-like method to diagonalize the Hermitian Hamiltonian matrix and derive analytically simplified neutrino oscillation probabilities for 3 (active) + 1 (sterile)-neutrino mixing for a constant matter density. These approximations can reach a considerably high numerical accuracy while retaining their analytical simplicity and fast computing speed. This would be useful for current and future long baseline neutrino oscillation experiments.
The Thomas theorem and the Efimov States within a generalized Bohr model
Authors: Zheng H , Bonasera A
Published: August 2020

Using a generalized Bohr model and the hyper-spherical formalism for a three-body system, we derive the universal energy functions. We apply our model to 4He atom where only the Coulomb potential is dominant and find that its binding energy is well reproduced (less than 5.5% difference). Later, we focus on the equal mass three-body systems and derive the Thomas theorem assuming a simple interaction depending on the range of the potential. We discuss the conditions for which an unbound two-body system produces a bound three-body system and apply our model to 4He and triton atoms as well as to the triton nucleus. Using their scattering lengths and effective ranges, we are able to reproduce the two-body or the three-body binding energies (less than 5% difference) with only one parameter fitted. Prediction for excited (Efimov) levels are also given and in particular we demonstrate that for some hyper-angles two equal minima appear which indicate a phase (shape) transition similar to the Landau’s theory of phase transition. We suggest that the observed excited levels in two different experiments for the triton nucleus are indeed Efimov levels and there may be more surprises.
The fundamental theorem of simple harmonic functions
Authors: Arekat Safwan
Published: August 2020

The defining relation for a one-dimensional real-valued simple harmonic function designated as

 
c
i
n
e

\ cine

(pronounced “scene” and symbolized

c
i
n

(
x
)

cin\left (x\right )

) is introduced as

d

d
x

c
i
n

(
x
)

=
c
i
n

(
x
+
p
)

\frac {d}{dx}cin\left (x\right )=cin\left (x+p\right )

. It is theorized that this definition of the derivative as the function itself translated on the real line by a certain positive number

p
p

is a sufficient condition for proving that

c
i
n

(
x
)

cin\left (x\right )

also satisfies the one-dimensional oscillator equation

d
2

d

x
2

c
i
n

(
x
)

=
−
 
c
i
n

(
x
)

\frac {d^2}{dx^2}cin\left (x\right )=-\ cin\left (x\right )

. A proof of this hypothesis is provided by establishing the continuity, differential, and boundedness properties of

c
i
n

(
x
)

cin\left (x\right )

and all of its higher-order derivatives and antiderivatives, while relying critically on Roe’s characterization of the sine function. The

c
i
n
e

cine

function enables the adoption of independent non-circular definitions of the trigonometric functions

s
i
n
e

sine

and

c
o
s
i
n
e

cosine

. The properties of

c
i
n
e

cine

are investigated, and trigonometric symmetries and identities are derived directly from the defining relation and its corollaries. A formulation for the unique solution of the function is proposed. Several useful operational theorems are stated and proved. The function is applied to solve problems in trigonometry and physics.
Positivity preservers forbidden to operate on diagonal blocks
Authors: Vishwakarma Prateek
Published: August 2020

The question of which functions acting entrywise preserve positive semidefiniteness has a long history, beginning with the Schur product theorem [Crelle 1911], which implies that absolutely monotonic functions (i.e., power series with nonnegative coefficients) preserve positivity on matrices of all dimensions. A famous result of Schoenberg and of Rudin [Duke Math. J. 1942, 1959] shows the converse: there are no other such functions.

Motivated by modern applications, Guillot and Rajaratnam [Trans. Amer. Math. Soc. 2015] classified the entrywise positivity preservers in all dimensions, which act only on the off-diagonal entries. These two results are at “opposite ends”, and in both cases the preservers have to be absolutely monotonic.

We complete the classification of positivity preservers that act entrywise except on specified “diagonal/principal blocks”, in every case other than the two above. (In fact we achieve this in a more general framework.) This yields the first examples of dimension-free entrywise positivity preservers - with certain forbidden principal blocks - that are not absolutely monotonic.
A geometric model of an arbitrary differentially closed field of characteristic zero
Authors: Spodzieja Stanisław
Published: August 2020

We give an elementary construction of an arbitrary differentially closed field and of a universal extension of a differential field in terms of Nash function fields. We also give a characterization of any Archimedean ordered differentially closed field in terms of Nash functions.
Screening instruments for cognitive impairment in older patients in the Emergency Department: a systematic review and meta-analysis
Authors: Calf Agneta H , Pouw Maaike A , van Munster Barbara C , Burgerhof Johannes G M , de Rooij Sophia E , Smidt Nynke
Published: August 2020

Background

cognitive impairment is highly prevalent among older patients attending the Emergency Department (ED) and is associated with adverse outcomes.

Methods

we conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of cognitive screening instruments to rule out cognitive impairment in older patients in the ED. A comprehensive literature search was performed in MEDLINE, EMBASE, CINAHL and CENTRAL. A risk of bias assessment using QUADAS-2 was performed.

Results

23 articles, examining 18 different index tests were included. Only seven index tests could be included in the meta-analysis. For ruling out cognitive impairment irrespective of aetiology, Ottawa 3 Day Year (O3DY) (pooled sensitivity 0.90; (95% CI) 0.71–0.97) had the highest sensitivity. Fourteen articles focused on screening for cognitive impairment specifically caused by delirium. For ruling out delirium, the 4 A’s Test (4AT) showed highest sensitivity (pooled sensitivity 0.87, 95% confidence interval (95% CI) 0.74–0.94).

Conclusions

high clinical and methodological heterogeneity was found between included studies. Therefore, it is a challenge to recommend one diagnostic test for use as a screening instrument for cognitive impairment in the ED. The 4AT and O3DY seem most promising for ruling out cognitive impairment in older patients attending the ED.

The review protocol was registered in PROSPERO (CRD42018082509).
The unique disarticulation layer formed in the rachis of Aegilops longissima probably results from the spatial co-expression of Btr1 and Btr2
Authors: Zeng Xiaoxue , Chen Gang , Wang Lei , Tagiri Akemi , Kikuchi Shinji , Sassa Hidenori , Komatsuda Takao
Published: August 2020

Background and Aims

The brittle rachis trait is a feature of many wild grasses, particularly within the tribe Triticeae. Wild Hordeum and Triticum species form a disarticulation layer above the rachis node, resulting in the production of wedge-type dispersal units. In Aegilops longissima, only one or two of the nodes in the central portion of its rachis are brittle. In Triticeae species, the formation of a disarticulation layer above the rachis node requires the co-transcription of the two dominant and complementary genes Btr1 and Btr2. This study aims to establish whether homologues of Btr1 and/or Btr2 underlie the unusual brittle rachis phenotype observed in Ae. longissima.

Methods

Scanning electron microscopy was used to examine the disarticulation surfaces. Quantitative RT-PCR and RNA in situ hybridization experiments were used to identify gene expression in the immature inflorescence.

Key Results

Analysis based on scanning electron microscopy was able to demonstrate that the disarticulation surfaces formed in the Ae. longissima rachis are morphologically indistinguishable from those formed in the rachises of wild Hordeum and Triticum species. RNA in situ hybridization showed that in the immature Ae. longissima inflorescence, the intensity of Btr1 transcription varied from high at the rachis base to low at its apex, while that of Btr2 was limited to the nodes in the central to distal portion of the rachis.

Conclusions

The disarticulation pattern shown by Ae. longissima results from the limitation of Btr1 and Btr2 co-expression to nodes lying in the centre of the rachis.
The Association Between Functional Assessment and Structural Brain Biomarkers in an Ethnically Diverse Sample With Normal Cognition, Mild Cognitive Impairment, or Dementia
Authors: Arruda Fernanda , Rosselli Mónica , Greig Maria T , Loewenstein David A , Lang Merike , Torres Valeria L , Vélez-Uribe Idaly , Conniff Joshua , Barker Warren W , Curiel Rosie E , Adjouadi Malek , Duara Ranjan
Published: August 2020

Objective

To investigate the association between the functional activities questionnaire (FAQ) and brain biomarkers (bilateral hippocampal volume [HV], bilateral entorhinal volume [ERV], and entorhinal cortical thickness [ERT]) in cognitively normal (CN) individuals, mild cognitive impairment (MCI), or dementia.

Method

In total, 226 participants (137 females; mean age = 71.76, SD = 7.93; Hispanic Americans = 137; European Americans = 89) were assessed with a comprehensive clinical examination, a neuropsychological battery, a structural magnetic resonance imaging, and were classified as CN or diagnosed with MCI or dementia. Linear regression analyses examined the association between functional activities as measured by the FAQ on brain biomarkers, including HV, ERV, and ERT, controlling for age, education, global cognition, gender, and ethnicity.

Results

The FAQ significantly predicted HV, ERV, and ERT for the entire sample. However, this association was not significant for ERV and ERT when excluding the dementia group. The FAQ score remained a significant predictor of HV for the non-dementia group. Age, education, gender, ethnicity, Montreal Cognitive Assessment score, and FAQ were also significant predictors of HV for the overall sample, suggesting that younger Hispanic females with fewer years of education, higher global mental status, and better functioning, were more likely to have larger HV.

Conclusion

FAQ scores were related to HV in older adults across clinical groups (CN, MCI, and dementia), but its association with the entorhinal cortex was driven by individuals with dementia. Demographic variables, including ethnicity, additionally influenced these associations.
Home-Based Pediatric Teleneuropsychology: A validation study
Authors: Harder Lana , Hernandez Ana , Hague Cole , Neumann Joy , McCreary Morgan , Cullum C Munro , Greenberg Benjamin
Published: August 2020

Objective

To evaluate home-based teleneuropsychology in a pediatric cohort to determine if assessment via in-person and home-based videoconference yield similar results. The second objective was to determine the level of satisfaction with videoconference-based assessment among participants and caregivers.

Method

Fifty-eight participants, aged 6–20 years, were recruited through specialty programs for pediatric demyelinating disorders. Each participant was administered the same brief neuropsychological battery of common measures twice, once during an in-person session and once during a remote home-based videoconference session. Order of sessions was counterbalanced and time between assessments ranged from 1 to 50 days. It was hypothesized that results obtained through in-person vs. remote videoconference sessions would not be significantly different and that most participants and caregivers would rate the experience with teleneuropsychology as satisfactory.

Results

Mann–Whitney U tests showed no significant differences in results obtained in the in-person first vs. remote videoconference first sessions or the change in performance across sessions. Satisfaction ratings by participants and caregivers were largely favorable for the use of the videoconference testing format.

Conclusions

The current study is the first to validate home-based teleneuropsychology and is the first to validate teleneuropsychological assessment in a pediatric sample. Future studies should replicate these findings as well as expand on sample size, diversity of populations evaluated, and the assessment tools administered. Careful consideration of ethical and practical factors should be given before providing pediatric teleneuropsychology services.
BSAseq: an interactive and integrated web-based workflow for identification of causal mutations in bulked F2 populations
Authors: Wang Liya , Lu Zhenyuan , Regulski Michael , Jiao Yinping , Chen Junping , Ware Doreen , Xin Zhanguo
Published: August 2020

With the advance of next-generation sequencing technologies and reductions in the costs of these techniques, bulked segregant analysis (BSA) has become not only a powerful tool for mapping quantitative trait loci but also a useful way to identify causal gene mutations underlying phenotypes of interest. However, due to the presence of background mutations and errors in sequencing, genotyping, and reference assembly, it is often difficult to distinguish true causal mutations from background mutations. In this study, we developed the BSAseq workflow, which includes an automated bioinformatics analysis pipeline with a probabilistic model for estimating the linked region (the region linked to the causal mutation) and an interactive Shiny web application for visualizing the results. We deeply sequenced a sorghum male-sterile parental line (ms8) to capture the majority of background mutations in our bulked F2 data. We applied the workflow to 11 bulked sorghum F2 populations and 1 rice F2 population and identified the true causal mutation in each population. The workflow is intuitive and straightforward, facilitating its adoption by users without bioinformatics analysis skills. We anticipate that the BSAseq workflow will be broadly applicable to the identification of causal mutations for many phenotypes of interest.

Availability and implementation

BSAseq is freely available on https://www.sciapps.org/page/bsa.

Supplementary information

Supplementary data are available at Bioinformatics online.
CONAN: a web application to detect specificity determinants and functional sites by amino acids co-variation network analysis
Authors: Fonseca N J , Afonso M Q L , Carrijo L , Bleicher L
Published: August 2020

CONAN is a web application developed to detect specificity determinants and function-related sites by amino acids co-variation networks analysis, emphasizing local coevolutionary constraints. The software allows the characterization of structurally and functionally relevant groups of residues and their relationship with subsets of sequences by automatic cross-referencing with GO terms, UniprotKb annotations and INTERPRO.

Availability and implementation

CONAN is free and open-source, being distributed in the terms of the GPLV3 license. The software is available as a web application and python script versions and can be accessed at http://bioinfo.icb.ufmg.br/conan. We also provide running instructions, the source code and a user guide.
Mutation-Simulator: fine-grained simulation of random mutations in any genome
Authors: Kühl M A , Stich B , Ries D C
Published: August 2020

Mutation-Simulator allows the introduction of various types of sequence alterations in reference sequences, with reasonable compute-time even for large eukaryotic genomes. Its intuitive system for fine-grained control over mutation rates along the sequence enables the mimicking of natural mutation patterns. Using standard file formats for input and output data, it can easily be integrated into any development and benchmarking workflow for high-throughput sequencing applications.

Availability and implementation

Mutation-Simulator is written in Python 3 and the source code, documentation, help and use cases are available on the Github page at https://github.com/mkpython3/Mutation-Simulator. It is free for use under the GPL 3 license.
Social Work Research in Chile: Tensions and Challenges under the ‘Knowledge Economy’ and Managerialist Research Agendas
Authors: Muñoz-Arce Gianinna , Rubilar-Donoso Gabriela
Published: August 2020

Research has been a contested dimension of Chilean social work. An important turn occurred in 2008 when Chilean national research policies—highly influenced by managerialist approaches—increased opportunities for social workers to conduct research. Several efforts have been made by academics and professional social work organisations to encourage research as a means of gaining recognition as a discipline. Drawing upon a thematic literature review from a Chilean-based study on social workers’ research trajectories, this article contends that, despite the value of such efforts, there are some tensions related to the acritical adoption of such a managerialist approach on social work research that need further attention: (i) research does not have the same value for all social work sectors; (ii) social work research is mainly understood as ‘academic’ research; and (iii) social workers’ research does not necessarily have a ‘social work focus’. These findings are discussed in light of the historical background of Chilean social work and the insights provided by the international literature, from which we conclude that the creation of more inclusive and collaborative ways of conducting research is an urgent challenge. Findings are context-specific, yet, offer considerations for social work research seeking to counteract managerial approaches of knowledge production.
Mitochondrial UQCRC1 mutations cause autosomal dominant parkinsonism with polyneuropathy
Authors: Lin Chin-Hsien , Tsai Pei-I , Lin Han-Yi , Hattori Nobutaka , Funayama Manabu , Jeon Beomseok , Sato Kota , Abe Koji , Mukai Yohei , Takahashi Yuji , Li Yuanzhe , Nishioka Kenya , Yoshino Hiroyo , Daida Kensuke , Chen Meng-Ling , Cheng Jay , Huang Cheng-Yen , Tzeng Shiou-Ru , Wu Yen-Sheng , Lai Hsing-Jung , Tsai Hsin-Hsi , Yen Ruoh-Fang , Lee Ni-Chung , Lo Wen-Chun , Hung Yu-Chien , Chan Chih-Chiang , Ke Yi-Ci , Chao Chi-Chao , Hsieh Sung-Tsang , Farrer Matthew , Wu Ruey-Meei
Published: August 2020

Parkinson’s disease is a neurodegenerative disorder with a multifactorial aetiology. Nevertheless, the genetic predisposition in many families with multi-incidence disease remains unknown. This study aimed to identify novel genes that cause familial Parkinson’s disease. Whole exome sequencing was performed in three affected members of the index family with a late-onset autosomal-dominant parkinsonism and polyneuropathy. We identified a novel heterozygous substitution c.941A>C (p.Tyr314Ser) in the mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) gene, which co-segregates with disease within the family. Additional analysis of 699 unrelated Parkinson’s disease probands with autosomal-dominant Parkinson’s disease and 1934 patients with sporadic Parkinson’s disease revealed another two variants in UQCRC1 in the probands with familial Parkinson’s disease, c.931A>C (p.Ile311Leu) and an allele with concomitant splicing mutation (c.70-1G>A) and a frameshift insertion (c.73_74insG, p.Ala25Glyfs*27). All substitutions were absent in 1077 controls and the Taiwan Biobank exome database from healthy participants (n = 1517 exomes). We then assayed the pathogenicity of the identified rare variants using CRISPR/Cas9-based knock-in human dopaminergic SH-SY5Y cell lines, Drosophila and mouse models. Mutant UQCRC1 expression leads to neurite degeneration and mitochondrial respiratory chain dysfunction in SH-SY5Y cells. UQCRC1 p.Tyr314Ser knock-in Drosophila and mouse models exhibit age-dependent locomotor defects, dopaminergic neuronal loss, peripheral neuropathy, impaired respiratory chain complex III activity and aberrant mitochondrial ultrastructures in nigral neurons. Furthermore, intraperitoneal injection of levodopa could significantly improve the motor dysfunction in UQCRC1 p.Tyr314Ser mutant knock-in mice. Taken together, our in vitro and in vivo studies support the functional pathogenicity of rare UQCRC1 variants in familial parkinsonism. Our findings expand an additional link of mitochondrial complex III dysfunction in Parkinson’s disease.
Quality by Design Approach to Develop Stability Indicating Method to Quantify Related Substances and Degradation Products of Sacubitril by High Performance Liquid Chromatography
Authors: Bommi Sivaganesh , Jayanty Subbalakshmi , Tirumalaraju Satyanarayana Raju , Bandaru Sivasankar
Published: August 2020

Sacubitril (SBT) is a neprilysin inhibitor, approved by food and drug administration (FDA) in 2015, under the FDA’s priority review process. In this work, we report the validated stability indicating method of SBT by employing quality by design (QbD) principles related to analytical method development, capable in separation of 11 impurities. Chromatographic separation was performed on an ascentis phenyl hexyl column using 10 mM KH2PO4 as a mobile phase-A and the pH adjusted to 2.1. Methanol: acetonitrile (70:30 v/v) solvent mixture was employed as the mobile phase-B in a gradient mode of elution at a flow rate 0.8 mL/min at 30°C. The column effluents were monitored by a photo diode array detector set at a wavelength of maximum absorption 254 nm noted for all the impurities and furthermore for SBT. This method was remarked to be accurate in the range from 92 to 116%, precise with relative standard deviation 0.9% for SBT (0.8 mg/mL) and 1.0 to 2.1% for its related impurities (0.0005 mg/mL) also linear with correlation coefficient r ≥ 0.9989. The limits of quantification for all impurities were 0.05% with respect to sample concentration 0.8 mg/mL. The developed method revealed a good method operable design range for the experimental chromatographic conditions. Forced degradation of SBT carried under acidic, basic and oxidative stressed conditions manifested that the method is stability indicating.
Are All Patients with Cancer at Heightened Risk for Severe Coronavirus Disease 2019 (COVID-19)?
Authors: Chamilos Georgios , Lionakis Michail S , Kontoyiannis Dimitrios P
Published: August 2020

Cancer patients are traditionally considered at high risk for complicated respiratory viral infections, due to their underlying immunosuppression. In line with this notion, early case series reported high mortality rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with malignancy. However, subsequent large, prospective, epidemiological surveys indicate that the risk for severe coronavirus disease 2019 (COVID-19) may be largely attributed to the multiple confounders operating in this highly heterogeneous population of patients, rather than the cancer or its treatment per se. We critically discuss the conundrums of SARS-CoV-2 infection in cancer patients and underscore mechanistic insights on the outcome of COVID-19 as it relates to cancer therapy and the type and status of the underlying malignancy. Not all cancer patients are similarly at risk for a complicated COVID-19 course. A roadmap is needed for translational and clinical research on COVID-19 in this challenging group of patients.
Clinical Characteristics and Predictors of Outcomes of Hospitalized Patients With Coronavirus Disease 2019 in a Multiethnic London National Health Service Trust: A Retrospective Cohort Study
Authors: Perez-Guzman Pablo N , Daunt Anna , Mukherjee Sujit , Crook Peter , Forlano Roberta , Kont Mara D , Løchen Alessandra , Vollmer Michaela , Middleton Paul , Judge Rebekah , Harlow Christopher , Soubieres Anet , Cooke Graham , White Peter J , Hallett Timothy B , Aylin Paul , Ferguson Neil , Hauck Katharina , Thursz Mark R , Nayagam Shevanthi
Published: August 2020

Background

Emerging evidence suggests ethnic minorities are disproportionately affected by coronavirus disease 2019 (COVID-19). Detailed clinical analyses of multicultural hospitalized patient cohorts remain largely undescribed.

Methods

We performed regression, survival, and cumulative competing risk analyses to evaluate factors associated with mortality in patients admitted for COVID-19 in 3 large London hospitals between 25 February and 5 April, censored as of 1 May 2020.

Results

Of 614 patients (median age, 69 [interquartile range, 25] years) and 62% male), 381 (62%) were discharged alive, 178 (29%) died, and 55 (9%) remained hospitalized at censoring. Severe hypoxemia (adjusted odds ratio [aOR], 4.25 [95% confidence interval {CI}, 2.36–7.64]), leukocytosis (aOR, 2.35 [95% CI, 1.35–4.11]), thrombocytopenia (aOR [1.01, 95% CI, 1.00–1.01], increase per 109 decrease), severe renal impairment (aOR, 5.14 [95% CI, 2.65–9.97]), and low albumin (aOR, 1.06 [95% CI, 1.02–1.09], increase per gram decrease) were associated with death. Forty percent (n = 244) were from black, Asian, and other minority ethnic (BAME) groups, 38% (n = 235) were white, and ethnicity was unknown for 22% (n = 135). BAME patients were younger and had fewer comorbidities. Although the unadjusted odds of death did not differ by ethnicity, when adjusting for age, sex, and comorbidities, black patients were at higher odds of death compared to whites (aOR, 1.69 [95% CI, 1.00–2.86]). This association was stronger when further adjusting for admission severity (aOR, 1.85 [95% CI, 1.06–3.24]).

Conclusions

BAME patients were overrepresented in our cohort; when accounting for demographic and clinical profile of admission, black patients were at increased odds of death. Further research is needed into biologic drivers of differences in COVID-19 outcomes by ethnicity.
Assessing the Potential for Unintended Microbial Consequences of Routine Chlorhexidine Bathing for Prevention of Healthcare-associated Infections
Authors: Babiker Ahmed , Lutgring Joseph D , Fridkin Scott , Hayden Mary K
Published: August 2020

Chlorhexidine gluconate (CHG) is an antiseptic that is widely used in healthcare due to its excellent safety profile and wide spectrum of activity. Daily bathing with CHG has proven to be effective in the prevention of healthcare-associated infections and multidrug-resistant pathogen decolonization. Despite the proven benefits of CHG use, there remain concerns and unanswered questions about the potential for unintended microbial consequences of routine CHG bathing. This review aims to explore some of these questions.
Plasma Chemokines Are Baseline Predictors of Unfavorable Treatment Outcomes in Pulmonary Tuberculosis
Authors: Kumar Nathella P , Moideen Kadar , Nancy Arul , Viswanathan Vijay , Thiruvengadam Kannan , Nair Dina , Banurekha Vaithilingam V , Sivakumar Shanmugam , Hissar Syed , Kornfeld Hardy , Babu Subash
Published: August 2020

Background

Plasma chemokines are biomarkers of greater disease severity, higher bacterial burden, and delayed sputum culture conversion in pulmonary tuberculosis (PTB). Whether plasma chemokines could also serve as biomarkers of unfavorable treatment outcomes in PTB is not known.

Methods

A cohort of newly diagnosed, sputum smear- and culture-positive adults with drug-sensitive PTB were recruited under the Effect of Diabetes on Tuberculosis Severity study in Chennai, India. Plasma chemokine levels measured before treatment initiation were compared between 68 cases with unfavorable outcomes (treatment failure, death, or recurrence) and 136 control individuals who had recurrence-free cure. A second validation cohort comprising newly diagnosed, culture-positive adults with drug-sensitive TB was used to measure plasma chemokine levels in 20 cases and 40 controls.

Results

Six chemokines (CCL2, CCL3, CCL4, CXCL8, CXCL10, and CX3CL1) were associated with increased risk, while CXCL1 was associated with decreased risk of unfavorable outcomes in unadjusted and adjusted analyses in the test cohort. Similarly, CCL3, CXCL8, and CXCL10 were associated with increased risk of unfavorable treatment outcomes in the validation cohort. Receiver operating characteristic analysis revealed that combinations of CCL3, CXCL8, and CXCL10 exhibited very high sensitivity and specificity in differentiating cases vs controls.

Conclusions

Our study reveals a plasma chemokine signature that can be used as a novel biomarker for predicting adverse treatment outcomes in PTB.
A Treatment-as-Prevention Trial to Eliminate Hepatitis C Among Men Who Have Sex With Men Living With Human Immunodeficiency Virus (HIV) in the Swiss HIV Cohort Study
Authors: Braun Dominique L , Hampel Benjamin , Ledergerber Bruno , Grube Christina , Nguyen Huyen , Künzler-Heule Patrizia , Shah Cyril , Salazar-Vizcaya Luisa , Conen Anna , Flepp Markus , Stöckle Marcel , Béguelin Charles , Schmid Patrick , Rougemont Mathieu , Delaloye Julie , Bernasconi Enos , Nicca Dunja , Böni Jürg , Rauch Andri , Kouyos Roger D , Günthard Huldrych F , Fehr Jan S
Published: August 2020

Background

In 2016, the World Health Organization (WHO) introduced global targets for the elimination of hepatitis C virus (HCV) by 2030. We conducted a nationwide HCV micro-elimination program among men who have sex with men (MSM) living with human immunodeficiency virus (HIV) from the Swiss HIV Cohort Study (SHCS) to test whether the WHO goals are achievable in this population.

Methods

During phase A (10/2015–06/2016), we performed a population-based and systematic screening for HCV-RNA among MSM from the SHCS. During phase B (06/2016–02/2017) we offered treatment with HCV direct-acting antiviral (DAA) agents to MSM identified with a replicating HCV infection. During phase C (03/2017–11/2017), we offered rescreening to all MSM for HCV-RNA and initiated DAA treatment in MSM with replicating infections.

Results

We screened 3715/4640 (80%) MSM and identified 177 with replicating HCV infections (4.8%); 150 (85%) of whom started DAA treatment and 149 (99.3%) were cured. We rescreened 2930/3538 (83%) MSM with a prior negative HCV-RNA and identified 13 (0.4%) with a new HCV infection. At the end of the micro-elimination program, 176/190 MSM (93%) were cured, and the HCV incidence rate declined from .53 per 100 patient-years (95% CI, .35–.83) prior to the intervention to .12 (95% CI, .03–.49) by the end of 2019.

Conclusions

A systematic, population-based HCV micro-elimination program among MSM living with HIV was feasible and resulted in a strong decline in HCV incidence and prevalence. Our study can serve as a model for other countries aiming to achieve the WHO HCV elimination targets.

Clinical Trials Registration

NCT02785666.
Sex Hormone Therapy and Tenofovir Diphosphate Concentration in Dried Blood Spots: Primary Results of the Interactions Between Antiretrovirals And Transgender Hormones Study
Authors: Grant Robert M , Pellegrini Marion , Defechereux Patricia A , Anderson Peter L , Yu Michelle , Glidden David V , O’Neal Joshua , Yager Jenna , Bhasin Shalender , Sevelius Jae , Deutsch Madeline B
Published: August 2020

Background

Sex hormone and preexposure prophylaxis (PrEP) drug interactions among transgender women (TGW), transgender men (TGM), and cisgender men (CGM) are not fully understood.

Methods

TGM and TGW on at least 6 months of stable sex hormone therapy containing testosterone or estradiol (respectively) were enrolled in a 4-week study of directly observed dosing of daily oral coformulated emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). TFV-DP in dried blood spots and sex hormones in serum were measured at weekly intervals. TFV-DP was compared with 2- and 4-week samples from Directly Observed Therapy Dried Blood Spots (DOT-DBS) Study (NCT02022657).

Results

From May 2017 to June 2018, 24 TGM and 24 TGW were enrolled. Testosterone (total and free) and estradiol concentrations were comparable before and after 4 weeks of PrEP use in TGM and TGW, respectively. Historical controls included 17 cisgender women (CGW) and 15 CGM. TFV-DP concentrations at week 4 were comparable between TGW and TGM (mean difference, −6%; 95% confidence interval [CI], −21% to 12%; P = .47), comparable between TGW and CGM (mean difference, −12%; 95% CI, −27% to 7%; P = .21) and were lower among TGM compared with CGW (mean difference, −23%; 95% CI, −36% to −7%; P = .007). All persons in all groups were projected to reach the TFV-DP threshold that has been associated with high protection from human immunodeficiency virus.

Conclusions

CGM, TGM, and TGW had comparable TFV-DP concentrations in dried blood spots after 4 weeks of directly observed daily FTC/TDF PrEP use. Serum hormone concentrations were not affected by FTC/TDF PrEP use.

Clinical Trials Registration

NCT04050371.
Veteran Women Living With Human Immunodeficiency Virus Have Increased Risk of Human Papillomavirus (HPV)-Associated Genital Tract Cancers
Authors: Clark Eva , Chen Liang , Dong Yongquan , Raychaudhury Suchismita , White Donna , Kramer Jennifer R , Chiao Elizabeth
Published: August 2020

Background

Disparities in access to screening often confound observed differences in human papillomavirus (HPV)-associated female genital tract cancer (FGTC) incidence between women living with human immunodeficiency virus (HIV; WLWH) and their HIV-negative counterparts. We aimed to determine if there have been changes in cancer risk among WLWH during the antiretroviral era in a single-payer health system.

Methods

We retrospectively selected WLWH and HIV-negative controls receiving care between 1999 and 2016 at the US Department of Veterans Affairs (VA) and identified FGTC diagnoses via Cancer Registry and International Classification of Diseases-9/10 codes. We extracted demographic and clinical variables from the VA’s Corporate Data Warehouse; evaluated incidence rates (IRs), incidence rate ratios, hazard ratios, and 95% confidence intervals (CIs) for cancer risk; and conducted survival analyses.

Results

We identified 1454 WLWH and compared them with 5816 matched HIV-negative controls. More WLWH developed HPV-associated FGTCs (total n = 28 [2.0%]; cervical = 22, vulvovaginal = 4, and anal/rectal = 2) than HIV-negative women (total n = 32 [0.6%]; cervical = 24, vulvovaginal = 5, and anal/rectal = 5) (log rank P < .0001). Cervical cancer IR was >6-fold higher for WLWH (204.2 per 100 000 person-years [py] [95% CI, 83.8–324.7]) than HIV-negative women (IR = 31.2 per 100 000 py [95% CI, 17.9–44.5]). The IRs for vulvovaginal and anal cancers were also higher in WLWH. Overall, WLWH were more likely to develop HPV-associated FGTCs compared with their HIV-negative counterparts (all log rank P values < .0001).

Conclusions

Veteran WLWH are more likely to develop HPV-associated FGTCs despite equal access to health care. Even in single-payer health systems, WLWH continue to require special attention to ensure guideline-based high-risk HPV screening for prevention of FGTCs.
Wrapper-Enabled Feature Selection and CPLM-Based NARX Model for Stock Market Prediction
Authors: Gandhmal Dattatray P , Kumar K
Published: August 2020

The prices in the stock market are dynamic in nature, thereby pretend as a hectic challenge to the sellers and buyers in predicting the trending stocks for the future. To ensure effective prediction of the stock market, the chronological penguin Levenberg–Marquardt-based nonlinear autoregressive network (CPLM-based NARX) is employed, and the prediction is devised on the basis of past and the recent rank of market. Initially, input data are subjected to the features extraction that is based on the technical indicators, such as WILLR, ROCR, MOM, RSI, CCI, ADX, TRIX, MACD, OBV, TSF, ATR and MFI. The technical indicator is adapted for predicting the stock market. The wrapper-enabled feature selection is employed for selecting the highly significant features that are generated using the technical indicators. The highly significant features of the data are fed to the prediction module, which is developed using the NARX model. The NARX model uses the CPLM algorithm that is formed using the integration of the chronological-based penguin search optimization algorithm and the Levenberg–Marquardt algorithm. The prediction using the proposed CPLM-based NARX shows the superior performance in terms of mean absolute percentage error and root mean square error with values of 0.96 and 0.805, respectively.
FLUTE: Fast and reliable knowledge retrieval from biomedical literature
Authors: Holtzapple Emilee , Telmer Cheryl A , Miskov-Zivanov Natasa
Published: August 2020

State-of-the-art machine reading methods extract, in hours, hundreds of thousands of events from the biomedical literature. However, many of the extracted biomolecular interactions are incorrect or not relevant for computational modeling of a system of interest. Therefore, rapid, automated methods are required to filter and select accurate and useful information. The FiLter for Understanding True Events (FLUTE) tool uses public protein interaction databases to filter interactions that have been extracted by machines from databases such as PubMed and score them for accuracy. Confidence in the interactions allows for rapid and accurate model assembly. As our results show, FLUTE can reliably determine the confidence in the biomolecular interactions extracted by fast machine readers and at the same time provide a speedup in interaction filtering by three orders of magnitude.

Database URL: https://bitbucket.org/biodesignlab/flute.
EnzyMine: a comprehensive database for enzyme function annotation with enzymatic reaction chemical feature
Authors: Sun Dandan , Cheng Xingxiang , Tian Yu , Ding Shaozhen , Zhang Dachuan , Cai Pengli , Hu Qian-nan
Published: August 2020

Addition of chemical structural information in enzymatic reactions has proven to be significant for accurate enzyme function prediction. However, such chemical data lack systematic feature mining and hardly exist in enzyme-related databases. Therefore, global mining of enzymatic reactions will offer a unique landscape for researchers to understand the basic functional mechanisms of natural bioprocesses and facilitate enzyme function annotation. Here, we established a new knowledge base called EnzyMine, through which we propose to elucidate enzymatic reaction features and then link them with sequence and structural annotations. EnzyMine represents an advanced database that extends enzyme knowledge by incorporating reaction chemical feature strategies, strengthening the connectivity between enzyme and metabolic reactions. Therefore, it has the potential to reveal many new metabolic pathways involved with given enzymes, as well as expand enzyme function annotation.

Database URL: http://www.rxnfinder.org/enzymine/
Edoxaban for stroke prevention in atrial fibrillation in routine clinical care: 1-year follow-up of the prospective observational ETNA-AF-Europe study
Authors: de Groot Joris R , Weiss Thomas W , Kelly Peter , Monteiro Pedro , Deharo Jean Claude , de Asmundis Carlo , López-de-Sá Esteban , Waltenberger Johannes , Steffel Jan , Levy Pierre , Bakhai Ameet , Zierhut Wolfgang , Laeis Petra , Manu Marius Constantin , Reimitz Paul-Egbert , De Caterina Raffaele , Kirchhof Paulus
Published: August 2020

Aims

Non-vitamin K oral anticoagulants are safe and effective for stroke prevention in patients with atrial fibrillation (AF). Data on the safety and efficacy of edoxaban in routine care are limited in Europe. We report 1-year outcomes in patients with AF treated with edoxaban in routine care.

Methods and results

ETNA-AF-Europe is a prospective, multicentre, post-authorization, observational study enrolling patients treated with edoxaban in 10 European countries, the design of which was agreed with the European Medicines Agency as part of edoxaban’s post-approval safety plan. Altogether 13 092 patients in 852 sites completed the 1-year follow-up [mean age: 73.6 ± 9.5 years; 57% male, mean follow-up: 352 ± 49 days (median: 366 days)]. Most patients had associated comorbidities (mean CHA2DS2-VASc score: 3.1 ± 1.4). Stroke or systemic embolism was reported in 103 patients (annualized event rate: 0.82%/year), and major bleeding events were reported in 132 patients (1.05%/year). Rates of intracranial haemorrhage were low [30 patients (0.24%/year)]. Death occurred in 442 patients (3.50%/year); cardiovascular (CV) death occurred in 206 patients (1.63%/year). The approved dosing of edoxaban was chosen in 83%. All-cause and CV mortality were higher in patients receiving edoxaban 30 mg vs. 60 mg, in line with the higher age and more frequent comorbidities of the 30 mg group. Major bleeding was also numerically more common in patients receiving edoxaban 30 mg vs. 60 mg.

Conclusion

The rates of stroke, systemic embolism, and major bleeding are low in this large unselected cohort of high-risk AF patients routinely treated with edoxaban.