bluuebunny/crossref_metadata_2025 huggingface dataset:
Geometry of error amplification in solving the Prony system with near-colliding nodes
Authors: Akinshin Andrey , Goldman Gil , Yomdin Yosef
Published: September 2020

We consider a reconstruction problem for “spike-train” signals

F
F

of an a priori known form

F
(
x
)
=

∑

j
=
1

d

a

j

δ

(
x
−

x

j

)

,

F(x)=\sum _{j=1}^{d}a_{j}\delta \left (x-x_{j}\right ),

from their moments

m
k

(
F
)
=
∫

x
k

F
(
x
)
d
x
.

m_k(F)=\int x^kF(x)dx.

We assume that the moments

m
k

(
F
)

m_k(F)

,

k
=
0
,
1
,
…
,
2
d
−
1

k=0,1,\ldots ,2d-1

, are known with an absolute error not exceeding

ϵ
>
0

\epsilon > 0

. This problem is essentially equivalent to solving the Prony system
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="sigma-summation Underscript j equals 1 Overscript d Endscripts a Subscript j Baseline x Subscript j Superscript k Baseline equals m Subscript k Baseline left-parenthesis upper F right-parenthesis comma k equals 0 comma 1 comma ellipsis comma 2 d minus 1 period">

∑

j
=
1

d

a
j

x
j
k

=

m
k

(
F
)
,
 
k
=
0
,
1
,
…
,
2
d
−
1.

\sum _{j=1}^d a_jx_j^k=m_k(F), \ k=0,1,\ldots ,2d-1.

We study the “geometry of error amplification” in reconstruction of

F
F

from

m
k

(
F
)
,

m_k(F),

in situations where the nodes

x
1

,
…
,

x
d

x_1,\ldots ,x_d

near-collide, i.e., form a cluster of size

h
≪
1

h \ll 1

. We show that in this case, error amplification is governed by certain algebraic varieties in the parameter space of signals

F
F

, which we call the “Prony varieties”.

Based on this we produce lower and upper bounds, of the same order, on the worst case reconstruction error. In addition we derive separate lower and upper bounds on the reconstruction of the amplitudes and the nodes.

Finally we discuss how to use the geometry of the Prony varieties to improve the reconstruction accuracy given additional a priori information.
Global Seasonal Influenza Mortality Estimates: A Comparison of 3 Different Approaches
Authors: Cozza Vanessa , Campbell Harry , Chang Howard H , Iuliano A Danielle , Paget John , Patel Neha N , Reiner Robert C , Troeger Chris , Viboud Cecile , Bresee Joseph S , Fitzner Julia
Published: September 2020

Prior to updating global influenza-associated mortality estimates, the World Health Organization convened a consultation in July 2017 to understand differences in methodology and implications for results of 3 influenza mortality projects from the US Centers for Disease Control and Prevention (CDC), the Netherlands Institute for Health Service Research’s Global Pandemic Mortality Project II (GLaMOR), and the Institute for Health Metrics and Evaluation (IHME). The expert panel reviewed estimates and discussed differences in data sources, analysis, and modeling assumptions. We performed a comparison analysis of the estimates. Influenza-associated respiratory death counts were comparable between CDC and GLaMOR; the IHME estimate was considerably lower. The greatest country-specific influenza-associated fold differences in mortality rate between CDC and IHME estimates and between GLaMOR and IHME estimates were among countries in Southeast Asia and the Eastern Mediterranean region. The data envelope used for the calculation was one of the major differences (CDC and GLaMOR: all respiratory deaths; IHME: lower-respiratory infection deaths). With the assumption that there is only one cause of death for each death, IHME estimates a fraction of the full influenza-associated respiratory mortality that is measured by the other 2 groups. Wide variability of parameters was observed. Continued coordination between groups could assist with better understanding of methodological differences and new approaches to estimating influenza deaths globally.
Genealogies Beyond Modernities
Authors: Ernest John
Published: September 2020

This essay is a response to six essays, and Derrick Spires’s introductory essay, gathered under the title “Genealogies of Black Modernity.” I argue against the usefulness of “modernity” as an organizing concept for the histories, global networks, publishing ventures, and scholarly initiatives explored in these essays, suggesting instead that we attend to the genealogies of a complex emergence for which we do not yet have an adequate descriptive framework. This is an emergence that challenges our usual approaches to historical periodization, our established concepts of collective achievement, or our habitual ways of framing a scholarly mission. The essays gathered here do not offer any simple vision of a coherent scholarly mission beyond the need to be attentive to a project of historical recovery that is always in danger of conceptual marginalizations. I explore the implications of archives that both reveal and obscure the operations of white supremacy, and I consider historical recovery projects that are overburdened by the racial politics they mean to address. Taking seriously the determined inclusiveness of the Black studies project, beyond class divisions and traditional markers of historical significance, I consider the ethical demands of a scholarly project devoted to recovering a history, and a historical process, that represents the imagined community these scholars are committed to serving.

Accounting for the lower frequencies of the white supremacist project of modernity, it’s possible that we’ve underestimated the radicalism of the Black studies project as it pertains to those of us in literary and cultural studies.
Slippery flowers as a mechanism of defence against nectar-thieving ants
Authors: Takeda Kazuya , Kadokawa Tomoki , Kawakita Atsushi
Published: September 2020

Background and Aims

The great diversity of floral characteristics among animal-pollinated plants is commonly understood to be the result of coevolutionary interactions between plants and pollinators. Floral antagonists, such as nectar thieves, also have the potential to exert an influence upon the selection of floral characteristics, but adaptation against floral antagonists has attracted comparatively little attention. We found that the corollas of hornet-pollinated Codonopsis lanceolata (Campanulaceae) and the tepals of bee-pollinated Fritillaria koidzumiana (Liliaceae) are slippery to nectar-thieving ants living in the plant’s habitat; because the flowers of both species have exposed nectaries, slippery perianths may function as a defence against nectar-thieving ants.

Methods

We conducted a behavioural experiment and observed perianth surface microstructure by scanning electron microscopy to investigate the mechanism of slipperiness. Field experiments were conducted to test whether slippery perianths prevent floral entry by ants, and whether ant presence inside flowers affects pollination.

Key Results

Scanning electron microscopy observations indicated that the slippery surfaces were coated with epicuticular wax crystals. The perianths lost their slipperiness when wiped with hexane. Artificial bridging of the slippery surfaces using non-slippery materials allowed ants to enter flowers more frequently. Experimental introduction of live ants to the Codonopsis flowers evicted hornet pollinators and shortened the duration of pollinator visits. However, no statistical differences were found in the fruit or seed sets of flowers with and without ants.

Conclusions

Slippery perianths, most probably based on epicuticular wax crystals, prevent floral entry by ants that negatively affect pollinator behaviour. Experimental evidence of floral defence based on slippery surfaces is rare, but such a mode of defence may be widespread amongst flowering plants.
Bedtk: finding interval overlap with implicit interval tree
Authors: Li Heng , Rong Jiazhen
Published: September 2020

We present bedtk, a new toolkit for manipulating genomic intervals in the BED format. It supports sorting, merging, intersection, subtraction and the calculation of the breadth of coverage. Bedtk uses implicit interval tree, a data structure for fast interval overlap queries. It is several to tens of times faster than existing tools and tends to use less memory.

Availability and implementation

The source code is available at https://github.com/lh3/bedtk.
Transforming growth factor beta signaling and decidual integrity in mice†
Authors: Fang Xin , Ni Nan , Gao Yang , Lydon John P , Ivanov Ivan , Rijnkels Monique , Bayless Kayla J , Li Qinglei
Published: September 2020

Transforming growth factor beta (TGFβ) signaling regulates multifaceted reproductive processes. It has been shown that the type 1 receptor of TGFβ (TGFBR1) is indispensable for female reproductive tract development, implantation, placental development, and fertility. However, the role of TGFβ signaling in decidual development and function remains poorly defined. Our objective is to determine the impact of uterine-specific deletion of Tgfbr1 on decidual integrity, with a focus on the cellular and molecular properties of the decidua during development. Our results show that the developmental dynamics of the decidua is altered in TGFBR1 conditionally depleted uteri from embryonic day (E) 5.5 to E8.5, substantiated by downregulation of genes associated with inflammatory responses and uterine natural killer cell abundance, reduced presence of nondecidualized fibroblasts in the antimesometrial region, and altered decidual cell development. Notably, conditional ablation of TGFBR1 results in the formation of decidua containing more abundant alpha smooth muscle actin (ACTA2)-positive cells at the peripheral region of the antimesometrial side versus controls at E6.5–E8.5. This finding is corroborated by upregulation of a subset of smooth muscle marker genes in Tgfbr1 conditionally deleted decidua at E6.5 and E8.5. Moreover, increased cell proliferation and enhanced decidual ERK1/2 signaling were found in Tgfbr1 conditional knockout mice upon decidual regression. In summary, conditional ablation of TGFBR1 in the uterus profoundly impacts the cellular and molecular properties of the decidua. Our results suggest that TGFBR1 in uterine epithelial and stromal compartments is important for the integrity of the decidua, a transient but crucial structure that supports embryo development.
Prostaglandin I2 mediates weak vasodilatation in human placental microvessels
Authors: Feng Xueqin , Zhang Yingying , Zhang Yumeng , Yang Xiaojun , Man Dongmei , Lu Likui , Xu Ting , Liu Yanping , Yang Chunli , Li Huan , Qi Linglu , Su Hongyu , Zhou Xiuwen , Xu Zhice
Published: September 2020

Human placental vessels (HPVs) play important roles in the exchange of metabolites and oxygen in maternal-fetal circulation. Endothelial-derived prostacyclin (prostaglandin I2, PGI2) is a critical endothelial vasodilator in the body. However, the physiological and pharmacological functions of endothelial PGI2 in the human placenta are still unclear. Human, sheep, and rat blood vessels were used in this study. Unlike non-placental vessels (non-PVs), the PGI2 synthesis inhibitor tranylcypromine (TCP) did not modify 5-hydroxytryptamine (5-HT)-induced vascular contraction, indicating that endothelial-derived PGI2 was weak in PVs. Vascular responses to exogenous PGI2 showed slight relaxation followed by a significant contraction at a higher concentration in HPV, which was inhibited by the thromboxane-prostanoid (TP) receptors antagonist SQ-29,548. Testing PVs and non-PVs from sheep also showed similar functional results. More TP receptors than PGI2 (IP) receptors were observed in HPVs. The whole-cell K+ current density of HPVs was significantly weaker than that of non-PVs. This study demonstrated the specific characteristics of the placental endogenous endothelial PGI2 system and the patterns of placental vascular physiological/pharmacological response to exogenous PGI2, showing that placental endothelial PGI2 does not markedly contribute to vascular dilation in the human placenta, in notable contrast to non-PVs. The results provide crucial information for understanding the endothelial roles of HPVs, which may be helpful for further investigations of potential targets in the treatment of diseases such as preeclampsia.
Role of DNA damage and repair mechanisms in uterine fibroid/leiomyomas: a review
Authors: Toprani Sneh M , Kelkar Mane Varsha
Published: September 2020

There has been a significant annual increase in the number of cases of uterine leiomyomas or fibroids (UF) among women of all races and ages across the world. A fortune is usually spent by the healthcare sector for fibroid-related treatments and management. Molecular studies have established the higher mutational heterogeneity in UF as compared to normal myometrial cells. The contribution of DNA damage and defects in repair responses further increases the mutational burden on the cells. This in turn leads to genetic instability, associated with cancer risk and other adverse reproductive health outcomes. Such and many more growing bodies of literature have highlighted the genetic/molecular, biochemical and clinical aspects of UF; none the less there appear to be a lacuna bridging the bench to bed gap in addressing and preventing this disease. Presented here is an exhaustive review of not only the molecular mechanisms underlying the predisposition to the disease but also possible strategies to effectively diagnose, prevent, manage, and treat this disease.
Quasi-oracle estimation of heterogeneous treatment effects
Authors: Nie X , Wager S
Published: September 2020

Flexible estimation of heterogeneous treatment effects lies at the heart of many statistical applications, such as personalized medicine and optimal resource allocation. In this article we develop a general class of two-step algorithms for heterogeneous treatment effect estimation in observational studies. First, we estimate marginal effects and treatment propensities to form an objective function that isolates the causal component of the signal. Then, we optimize this data-adaptive objective function. The proposed approach has several advantages over existing methods. From a practical perspective, our method is flexible and easy to use: in both steps, any loss-minimization method can be employed, such as penalized regression, deep neural networks, or boosting; moreover, these methods can be fine-tuned by cross-validation. Meanwhile, in the case of penalized kernel regression, we show that our method has a quasi-oracle property. Even when the pilot estimates for marginal effects and treatment propensities are not particularly accurate, we achieve the same error bounds as an oracle with prior knowledge of these two nuisance components. We implement variants of our approach based on penalized regression, kernel ridge regression, and boosting in a variety of simulation set-ups, and observe promising performance relative to existing baselines.
In Their Own Words: Marvalee Wake
Authors: Verdier James M
Published: September 2020

In Their Own Words chronicles the stories of scientists who have made great contributions to their fields. These short histories provide our readers a way to learn from and share their experiences. Each month, we will publish in the pages of BioScience and on our podcast, BioScience Talks (http://bioscienceaibs.libsyn.com), the results of these conversations. This history is with Marvalee Wake, professor of the Graduate School in the Department of Integrative Biology at the University of California, Berkeley. She is also a past president of AIBS.

Note: Both the text and audio versions have been edited for clarity and length.
Leaving ‘home?’ Belonging, break-up and becoming in the police family
Authors: Atkinson Colin , Murray Kath
Published: September 2020

This article considers the impact of police merger processes on officers and staff. The Railway Policing (Scotland) Act 2017 legislated that the Scottish functions and personnel of the British Transport Police (BTP) would be integrated into Scotland’s national police force. The journey towards this destination, however, has been protracted, problematic and now appears to be indefinitely postponed. Demonstrating the limits of the ‘police family’, our research provides important policy insights, demonstrating how a failure to account for distinct organizational cultures and occupational identities can damage the legitimacy of police mergers. Using data from a survey of BTP officers and staff in Scotland, we present our findings across three themes: belonging; break-up and becoming. We refract these findings through Bourdieusian theory.
Meningeal blood–brain barrier disruption in acute traumatic brain injury
Authors: Turtzo Lisa Christine , Jikaria Neekita , Cota Martin R , Williford Joshua P , Uche Victoria , Davis Tara , MacLaren Judy , Moses Anita D , Parikh Gunjan , Castro Marcelo A , Pham Dzung L , Butman John A , Latour Lawrence L
Published: September 2020

The meninges serve as a functional barrier surrounding the brain, critical to the immune response, and can be compromised following head trauma. Meningeal enhancement can be detected on contrast-enhanced MRI in patients presenting with acute traumatic brain injury, even when head CT is negative. Following head trauma, gadolinium-based contrast appears to extravasate from the vasculature, enhancing the dura within minutes, and later permeates the subarachnoid space. The aims of this study were to characterize the initial kinetics of the uptake of contrast agent after injury and the delayed redistribution of contrast enhancement in the subarachnoid space in hyperacute patients. Neuroimaging was obtained prospectively in two large ongoing observational studies of patients aged 18 years or older presenting to the emergency department with suspected acute head injury. Dynamic contrast-enhanced MRI studies in a cohort of consecutively enrolling patients with mild traumatic brain injury (n = 36) determined that the kinetic half-life of dural-related meningeal enhancement was 1.3 ± 0.6 min (95% enhancement within 6 min). The extravasation of contrast into the subarachnoid space was investigated in a cohort of CT negative mild traumatic brain injury patients initially imaged within 6 h of injury (hyperacute) who subsequently underwent a delayed MRI, with no additional contrast administration, several hours after the initial MRI. Of the 32 patients with delayed post-contrast imaging, 18 (56%) had conspicuous expansion of the contrast enhancement into the subarachnoid space, predominantly along the falx and superior sagittal sinus. Patients negative for traumatic meningeal enhancement on initial hyperacute MRI continued to have no evidence of meningeal enhancement on the delayed MRI. These studies demonstrate that (i) the initial enhancement of the traumatically injured meninges occurs within minutes of contrast injection, suggesting highly permeable meningeal vasculature, and that (ii) contrast in the meninges redistributes within the subarachnoid space over the period of hours, suggesting a compromise in the blood–brain and/or blood-cerebrospinal barriers. Data from the parent study indicate that up to one in two patients with mild traumatic brain injury have traumatic brain injury on acute (<48 h) MRI, with a higher prevalence seen in patients with moderate or severe traumatic brain injury. The current study’s findings of traumatic meningeal enhancement and the subsequent delayed extravasation of contrast into the subarachnoid spaces indicate that a substantial percentage of patients with even mild traumatic brain injury may have a transient disruption in barriers separating the vasculature from the brain.
Dentate Gyrus Somatostatin Cells are Required for Contextual Discrimination During Episodic Memory Encoding
Authors: Morales Cristian , Morici Juan Facundo , Espinosa Nelson , Sacson Agostina , Lara-Vasquez Ariel , García-Pérez M A , Bekinschtein Pedro , Weisstaub Noelia V , Fuentealba Pablo
Published: September 2020

Memory systems ought to store and discriminate representations of similar experiences in order to efficiently guide future decisions. This problem is solved by pattern separation, implemented in the dentate gyrus (DG) by granule cells to support episodic memory formation. Pattern separation is enabled by tonic inhibitory bombardment generated by multiple GABAergic cell populations that strictly maintain low activity levels in granule cells. Somatostatin-expressing cells are one of those interneuron populations, selectively targeting the distal dendrites of granule cells, where cortical multimodal information reaches the DG. Nonetheless, somatostatin cells have very low connection probability and synaptic efficacy with both granule cells and other interneuron types. Hence, the role of somatostatin cells in DG circuitry, particularly in the context of pattern separation, remains uncertain. Here, by using optogenetic stimulation and behavioral tasks in mice, we demonstrate that somatostatin cells are required for the acquisition of both contextual and spatial overlapping memories.
SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes
Authors: Bojkova Denisa , Wagner Julian U G , Shumliakivska Mariana , Aslan Galip S , Saleem Umber , Hansen Arne , Luxán Guillermo , Günther Stefan , Pham Minh Duc , Krishnan Jaya , Harter Patrick N , Ermel Utz H , Frangakis Achilleas S , Milting Hendrik , Zeiher Andreas M , Klingel Karin , Cinatl Jindrich , Dendorfer Andreas , Eschenhagen Thomas , Tschöpe Carsten , Ciesek Sandra , Dimmeler Stefanie
Published: September 2020

Aims

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic. SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk of mortality. It is unclear whether cardiac injury is caused by direct infection of cardiomyocytes or is mainly secondary to lung injury and inflammation. Here, we investigate whether cardiomyocytes are permissive for SARS-CoV-2 infection.

Methods and results

Two strains of SARS-CoV-2 infected human induced pluripotent stem cell-derived cardiomyocytes as demonstrated by detection of intracellular double-stranded viral RNA and viral spike glycoprotein expression. Increasing concentrations of viral RNA are detected in supernatants of infected cardiomyocytes, which induced infections in Caco-2 cell lines, documenting productive infections. SARS-CoV-2 infection and induced cytotoxic and proapoptotic effects associated with it abolished cardiomyocyte beating. RNA sequencing confirmed a transcriptional response to viral infection as demonstrated by the up-regulation of genes associated with pathways related to viral response and interferon signalling, apoptosis, and reactive oxygen stress. SARS-CoV-2 infection and cardiotoxicity was confirmed in a 3D cardiosphere tissue model. Importantly, viral spike protein and viral particles were detected in living human heart slices after infection with SARS-CoV-2. Coronavirus particles were further observed in cardiomyocytes of a patient with coronavirus disease 2019. Infection of induced pluripotent stem cell-derived cardiomyocytes was dependent on cathepsins and angiotensin-converting enzyme 2, and was blocked by remdesivir.

Conclusion

This study demonstrates that SARS-CoV-2 infects cardiomyocytes in vitro in an angiotensin-converting enzyme 2- and cathepsin-dependent manner. SARS-CoV-2 infection of cardiomyocytes is inhibited by the antiviral drug remdesivir.
Effect of anastomotic leaks on long-term survival after oesophagectomy for oesophageal cancer: systematic review and meta-analysis
Authors: Gujjuri Rohan R , Kamarajah Sivesh K , Markar Sheraz R
Published: September 2020

Introduction

Long-term survival after curative surgery for oesophageal cancer surgery remains poor, and the prognostic impact of anastomotic leak (AL) remains unknown. A meta-analysis was conducted to investigate the impact of AL on long-term survival.

Methods

A systematic electronic search for articles was performed for studies published between 2001 and 2020 evaluating the long-term oncological impact of AL. Meta-analysis was performed using the DerSimonian-Laird random-effects model to compute hazard ratios and 95% confidence intervals.

Results

Nineteen studies met the inclusion criteria, yielding a total of 9885 patients. Long-term survival was significantly reduced after AL (HR: 1.79, 95% CI: 1.33–2.43). AL was associated with significantly reduced overall survival in studies within hospital volume Quintile 1 (HR: 1.35, 95% CI: 1.12–1.63) and Quintile 2 (HR: 1.83, 95% CI: 1.35–2.47). However, no significant association was found for studies within Quintile 3 (HR: 2.24, 95% CI: 0.85–5.88), Quintile 4 (HR: 2.59, 95% CI: 0.67–10.07), and Quintile 5 (HR: 1.29, 95% CI: 0.92–1.81). AL was significantly associated with poor long-term survival in patients with associated overall Clavien Dindo Grades 1–5 (HR: 2.17, 95% CI: 1.31–3.59) and severe Clavien Dindo Grades 3–5 (HR: 1.42, 95% CI: 1.14–1.78) complications.

Conclusions

AL has a negative prognostic impact on long-term survival after restorative resection of oesophageal cancers, particularly in low-volume centers. Future efforts must be focused on strategies to minimize the septic and immunological response to AL with early recognition and treatment thus reducing the impact on long-term survival.
Orthodontic treatment and root resorption: an overview of systematic reviews
Authors: Yassir Yassir A , McIntyre Grant T , Bearn David R
Published: September 2020

Background

Root resorption can be considered the most unfortunate complication of orthodontic treatment.

Objective

To evaluate the available evidence regarding orthodontically induced inflammatory root resorption (OIIRR).

Search methods

A comprehensive literature search was conducted for the systematic reviews investigating OIIRR published up to 24 May 2020. This was accomplished using electronic databases: MEDLINE via OVID, EMBASE, AMED (Allied and Complementary Medicine Database), PubMed, and Web of Science. Any ongoing systematic reviews were searched using Prospero and a grey literature search was undertaken using Google Scholar and OpenGrey (www.opengrey.eu/). No language restriction was applied.

Selection criteria

Only studies investigating OIIRR were included.

Data collection and analysis

Screening, quality assessment [using the AMSTAR 2 tool (A Measurement Tool to Assess Systematic Reviews)], and data extraction were performed by two authors independently. Information was categorized and narratively synthesized for the key findings from moderate and high-quality reviews.

Results

A total of 2033 potentially eligible studies were identified. After excluding the non-relevant studies, 28 systematic reviews were included. Of which, 20 systematic reviews (71.5%) were of moderate and high-quality level of evidence. The incidence and severity of OIIRR increase with the fixed appliance, especially with heavy force, intrusion, torqueing movements, increased treatment duration, and treatment with extractions or with long apical displacement (particularly for maxillary incisors). There was insufficient evidence regarding most other treatment- and patient-related factors on OIIRR. Following all precautionary measures, pausing treatment and regular monitoring benefits patients with OIIRR.

Conclusions and implications

There is a limited number of high-quality studies in terms of OIIRR. The influence of fixed appliance on root resorption was noted; however, the cause and effect relationship between OIIRR and orthodontic biomechanics has not been confirmed. Avoiding heavy, continuous forces and a greater amount of apical displacement over a long duration of treatment is recommended. Precautionary measures should be carefully considered when treating patients with a high risk of OIIRR.

Registration

CRD42020166629.
Animals and the prehistoric origins of economic development
Authors: Riahi Ideen A
Published: September 2020

This paper revisits the macro-level relationship between human genetic variation (genetic distance and diversity) and economic development. If other continents were biogeographically more similar to Eurasia, their populations’ capacities to ward off the adverse effects of European colonization would have been much higher and, thus, their economies considerably more prosperous today. At the continental scale, genetic differences between people do not matter for comparative development.
The one hundred year journey of the genus Brucella (Meyer and Shaw 1920)
Authors: Moreno Edgardo
Published: September 2020

The genus Brucella, described by Meyer and Shaw in 1920, comprises bacterial pathogens of veterinary and public health relevance. For 36 years, the genus came to include three species that caused brucellosis in livestock and humans. In the second half of the 20th century, bacteriologists discovered five new species and several ʻatypicalʼ strains in domestic animals and wildlife. In 1990, the Brucella species were recognized as part of the Class Alphaproteobacteria, clustering with pathogens and endosymbionts of animals and plants such as Bartonella, Agrobacterium and Ochrobactrum; all bacteria that live in close association with eukaryotic cells. Comparisons with Alphaproteobacteria contributed to identify virulence factors and to establish evolutionary relationships. Brucella members have two circular chromosomes, are devoid of plasmids, and display close genetic relatedness. A proposal, asserting that all brucellae belong to a single species with several subspecies debated for over 70 years, was ultimately rejected in 2006 by the subcommittee of taxonomy, based on scientific, practical, and biosafety considerations. Following this, the nomenclature of having multiples Brucella species prevailed and defined according to their molecular characteristics, host preference, and virulence. The 100-year history of the genus corresponds to the chronicle of scientific efforts and the struggle for understanding brucellosis.
Origin and Evolution of Fusidane-Type Antibiotics Biosynthetic Pathway through Multiple Horizontal Gene Transfers
Authors: Li Xiangchen , Cheng Jian , Liu Xiaonan , Guo Xiaoxian , Liu Yuqian , Fan Wenjing , Lu Lina , Ma Yanhe , Liu Tao , Tao Shiheng , Jiang Huifeng
Published: September 2020

Fusidane-type antibiotics represented by fusidic acid, helvolic acid, and cephalosporin P1 have very similar core structures, but they are produced by fungi belonging to different taxonomic groups. The origin and evolution of fusidane-type antibiotics biosynthetic gene clusters (BGCs) in different antibiotics producing strains remained an enigma. In this study, we investigated the distribution and evolution of the fusidane BGCs in 1,284 fungal genomes. We identified 12 helvolic acid BGCs, 4 fusidic acid BGCs, and 1 cephalosporin P1 BGC in Pezizomycotina fungi. Phylogenetic analyses indicated six horizontal gene transfer (HGT) events in the evolutionary trajectory of the BGCs, including 1) three transfers across Eurotiomycetes and Sordariomycetes classes; 2) one transfer between genera under Sordariomycetes class; and 3) two transfers within Aspergillus genus under Eurotiomycetes classes. Finally, we proposed that the ancestor of fusidane BGCs would be originated from the Zoopagomycota by ancient HGT events according to the phylogenetic trees of key enzymes in fusidane BGCs (OSC and P450 genes). Our results extensively clarify the evolutionary trajectory of fusidane BGCs by HGT among distantly related fungi and provide new insights into the evolutionary mechanisms of metabolic pathways in fungi.
Clinical implication of tumour spread through air spaces in pathological stage I lung adenocarcinoma treated with lobectomy
Authors: Yi Eunjue , Lee Jeong Hyeon , Jung Younggi , Chung Jae Ho , Lee Youngseok , Lee Sungho
Published: September 2020

OBJECTIVES

The aim of this study was to evaluate the clinical implication of tumour spread through air spaces (STAS) as a prognostic factor in pathological stage I lung adenocarcinoma treated with lobectomy and to identify related parameters.

METHODS

Medical records of patients who underwent pulmonary lobectomy for stage I (American Joint Committee on Cancers eighth edition) lung adenocarcinomas between 2012 and February 2018 at our institutions were reviewed retrospectively. Patients with minimally invasive adenocarcinomas and tumours ≥3 cm in size were excluded. Included patients were classified into STAS (+) and STAS (−) groups. Clinical implications of STAS and recurrence in patients were investigated.

RESULTS

A total of 109 patients was analysed: 41 (37.6%) in the STAS (+) and 68 (62.4%) in the STAS (−) group. STAS was associated with larger consolidation diameter on chest tomography (≥1.5 cm; P = 0.006) or a higher invasive ratio (≥85%; P = 0.012) and presence of a micropapillary pattern in multivariable analysis (P = 0.003) The recurrence-free survival curve showed statistical difference (P = 0.008) with 3-year survival rates of 73.0% (9 patients) and 96.8% (2 patients) in the STAS (+) and STAS (−) group, respectively. However, no statistical significance was observed in the lung cancer-related survival curve (P = 0.648). The presence of STAS was an independent risk factor for recurrence in multivariable analysis (hazard ratio = 5.9, P = 0.031).

CONCLUSIONS

The presence of STAS could be an important risk factor for recurrence in patients with early-stage invasive lung adenocarcinoma treated with pulmonary lobectomy.
Finite element convergence for the time-dependent Joule heating problem with mixed boundary conditions
Authors: Jensen Max , Målqvist Axel , Persson Anna
Published: September 2020

We prove strong convergence for a large class of finite element methods for the time-dependent Joule heating problem in three spatial dimensions with mixed boundary conditions on Lipschitz domains. We consider conforming subspaces for the spatial discretization and the backward Euler scheme for the temporal discretization. Furthermore, we prove uniqueness and higher regularity of the solution on creased domains and additional regularity in the interior of the domain. Due to a variational formulation with a cut-off functional, the convergence analysis does not require a discrete maximum principle, permitting approximation spaces suitable for adaptive mesh refinement, responding to the difference in regularity within the domain.
Guillain-Barré Syndrome After High-Dose Influenza Vaccine Administration in the United States, 2018–2019 Season
Authors: Perez-Vilar Silvia , Hu Mao , Weintraub Eric , Arya Deepa , Lufkin Bradley , Myers Tanya , Woo Emily Jane , Lo An-Chi , Chu Steve , Swarr Madeline , Liao Jiemin , Wernecke Michael , MaCurdy Tom , Kelman Jeffrey , Anderson Steven , Duffy Jonathan , Forshee Richard A
Published: September 2020

Background

The Vaccine Safety Datalink (VSD) identified a statistical signal for an increased risk of Guillain-Barré syndrome (GBS) in days 1–42 after 2018–2019 high-dose influenza vaccine (IIV3-HD) administration. We evaluated the signal using Medicare.

Methods

We conducted early- and end-of-season claims-based self-controlled risk interval analyses among Medicare beneficiaries ages ≥65 years, using days 8–21 and 1–42 postvaccination as risk windows and days 43–84 as control window. The VSD conducted chart-confirmed analyses.

Results

Among 7 453 690 IIV3-HD vaccinations, we did not detect a statistically significant increased GBS risk for either the 8- to 21-day (odds ratio [OR], 1.85; 95% confidence interval [CI], 0.99–3.44) or 1- to 42-day (OR, 1.31; 95% CI, 0.78–2.18) risk windows. The findings from the end-of-season analyses were fully consistent with the early-season analyses for both the 8- to 21-day (OR, 1.64; 95% CI, 0.92–2.91) and 1- to 42-day (OR, 1.12; 95% CI, 0.70–1.79) risk windows. The VSD’s chart-confirmed analysis, involving 646 996 IIV3-HD vaccinations, with 1 case each in the risk and control windows, yielded a relative risk of 1.00 (95% CI, 0.06–15.99).

Conclusions

The Medicare analyses did not exclude an association between IIV3-HD and GBS, but it determined that, if such a risk existed, it was similar in magnitude to prior seasons. Chart-confirmed VSD results did not confirm an increased risk of GBS.
The novel macrolide resistance genes mef(F) and msr(G) are located on a plasmid in Macrococcus canis and a transposon in Macrococcus caseolyticus
Authors: Fernandez Javier Eduardo , Perreten Vincent , Schwendener Sybille
Published: September 2020

Objectives

To analyse macrolide resistance in a Macrococcus canis strain isolated from a dog with an ear infection, and determine whether the resistance mechanism is also present in other bacteria, and associated with mobile genetic elements.

Methods

The whole genome of M. canis Epi0082 was sequenced using PacBio and Illumina technologies. Novel macrolide resistance determinants were identified through bioinformatic analysis, and functionality was demonstrated by expression in Staphylococcus aureus. Mobile genetic elements containing the novel genes were analysed in silico for strain Epi0082 as well as in other bacterial strains deposited in GenBank.

Results

M. canis Epi0082 contained a 3212 bp operon with the novel macrolide resistance genes mef(F) and msr(G) encoding a efflux protein and an ABC-F ribosomal protection protein, respectively. Cloning in S. aureus confirmed that both genes individually confer resistance to the 14- and 15-membered ring macrolides erythromycin and azithromycin, but not the 16-membered ring macrolide tylosin. A reduced susceptibility to the streptogramin B pristinamycin IA was additionally observed when msr(G) was expressed in S. aureus under erythromycin induction. Epi0082 carried the mef(F)–msr(G) operon together with the chloramphenicol resistance gene fexB in a novel 39 302 bp plasmid pMiCAN82a. The mef(F)–msr(G) operon was also found in macrolide-resistant Macrococcus caseolyticus strains in the GenBank database, but was situated in the chromosome as part of a novel 13 820 bp or 13 894 bp transposon Tn6776.

Conclusions

The identification of mef(F) and msr(G) on different mobile genetic elements in Macrococcus species indicates that these genes hold potential for further dissemination of resistance to the clinically important macrolides in the bacterial population.
Each patient is a research biorepository: informatics-enabled research on surplus clinical specimens via the living BioBank
Authors: Alekseyenko Alexander V , Hamidi Bashir , Faith Trevor D , Crandall Keith A , Powers Jennifer G , Metts Christopher L , Madory James E , Carroll Steven L , Obeid Jihad S , Lenert Leslie A
Published: September 2020

The ability to analyze human specimens is the pillar of modern-day translational research. To enhance the research availability of relevant clinical specimens, we developed the Living BioBank (LBB) solution, which allows for just-in-time capture and delivery of phenotyped surplus laboratory medicine specimens. The LBB is a system-of-systems integrating research feasibility databases in i2b2, a real-time clinical data warehouse, and an informatics system for institutional research services management (SPARC). LBB delivers deidentified clinical data and laboratory specimens. We further present an extension to our solution, the Living µBiome Bank, that allows the user to request and receive phenotyped specimen microbiome data. We discuss the details of the implementation of the LBB system and the necessary regulatory oversight for this solution. The conducted institutional focus group of translational investigators indicates an overall positive sentiment towards potential scientific results generated with the use of LBB. Reference implementation of LBB is available at https://LivingBioBank.musc.edu.
A Generalized Additive Model Correlating Blacklegged Ticks With White-Tailed Deer Density, Temperature, and Humidity in Maine, USA, 1990–2013
Authors: Elias Susan P , Gardner Allison M , Maasch Kirk A , Birkel Sean D , Anderson Norman T , Rand Peter W , Lubelczyk Charles B , Smith Robert P
Published: September 2020

Geographical range expansions of blacklegged tick [Ixodes scapularis Say (Acari: Ixodidae)] populations over time in the United States have been attributed to a mosaic of factors including 20th century reforestation followed by suburbanization, burgeoning populations of the white-tailed deer [Odocoileus virginianus Zimmerman (Artiodactyla: Cervidae)], and, at the northern edge of I. scapularis’ range, climate change. Maine, a high Lyme disease incidence state, has been experiencing warmer and shorter winter seasons, and relatively more so in its northern tier. Maine served as a case study to investigate the interacting impacts of deer and seasonal climatology on the spatial and temporal distribution of I. scapularis. A passive tick surveillance dataset indexed abundance of I. scapularis nymphs for the state, 1990–2013. With Maine’s wildlife management districts as the spatial unit, we used a generalized additive model to assess linear and nonlinear relationships between I. scapularis nymph abundance and predictors. Nymph submission rate increased with increasing deer densities up to ~5 deer/km2 (13 deer/mi2), but beyond this threshold did not vary with deer density. This corroborated the idea of a saturating relationship between I. scapularis and deer density. Nymphs also were associated with warmer minimum winter temperatures, earlier degree-day accumulation, and higher relative humidity. However, nymph abundance only increased with warmer winters and degree-day accumulation where deer density exceeded ~2 deer/km2 (~6/mi2). Anticipated increases in I. scapularis in the northern tier could be partially mitigated through deer herd management.
The Gray Area of Institutional Change: How the Security Council Transforms Its Practices on the Fly
Authors: Pouliot Vincent
Published: September 2020

In world politics, institutional development often takes place in a gray area that combines elements of rational design and organic change in practice. Faced with impracticable secondary rules, diplomats evolve semi-formal practices that allow them to make collectively binding decisions even in the absence of a procedure to do so, effectively building the plane while flying it. Changing practices at the United Nations Security Council offer a particularly significant and fertile case here. The ways in which the body conducts its business have significantly evolved in the post–Cold War era, though in the absence of formal changes to the Charter or the Council's Rules of Procedure. How is such a casual institutional transformation possible in the most politicized global governance body? Building on practitioners’ accounts, the article maps out the four spaces of semi-formality and the attendant practices by which the Council transforms itself. First, Council diplomats value flexibility and allow each other to innovate. Second, they attempt to codify evolving ways of conducting Council business. Third, a set of training practices allows for socialization in ways of doing things. Fourth and finally, diplomats on the Council have limited opportunities to collectively discuss their changing practices. Overall, the article suggests that gray zones are far more pervasive than currently acknowledged in world politics, calling for more scholarly interest in this hybrid mode of institutional change in which design emerges organically and is collectively owned.
PositiveMycobacterium tuberculosisGastric Lavage Cultures from Asymptomatic Children With Normal Chest Radiography
Authors: Donald Peter R , Ronge Lena , Demers Anne-Marie , Thee Stephanie , Schaaf H Simon , Hesseling Anneke C
Published: September 2020

Mycobacterium tuberculosis culture from gastric lavage from apparently healthy children following tuberculin skin test conversion, despite normal chest radiography (CR), is well known but is a contentious subject. A consensus statement regarding classification of childhood tuberculosis excluded this condition, stating that more data were needed. To assist in this discussion, we reviewed early publications that reported the occurrence of this phenomenon and early anatomical pathology studies that described changes that occur in children following tuberculosis infection. Pathology studies describe frequent cavitation in primary foci in children from whom positive M. tuberculosis cultures might easily arise. These foci were very small in some children who might have normal CR. Positive cultures might also arise from ulcerated mediastinal lymph nodes that are invisible on CR. Young children with recent infection very likely have active primary pulmonary tuberculosis.
Neuropsychiatry of consciousness
Authors: Linden David
Published: September 2020

Consciousness requires wakefulness and awareness. Many neuropsychiatric syndromes involve the disturbance of these functions. This chapter provides an overview of the various clinical presentations involving quantitative or qualitative disturbances of consciousness in order to explore the associated pathologies and underlying neurophysiological mechanisms. It lays out a number of clinical syndromes associated with impaired consciousness, such as persistent vegetative state (PVS) or unresponsive wakefulness syndrome (UWS), where the patient’s bodily functions can continue independently and show activity in higher motor areas when prompted under functional magnetic resonance imaging, yet are unable to communicate or follow commands. Focus is then given to altered mental states where conditions, such as neuroleptic malignant syndrome (NMS), may cause patients to experience depersonalization, fugue states, and hallucinations. After exploring the neuroanatomy and neurophysiology of such disorders, with a description of the function and significance of the ascending reticular activating system (ARAS), a number of clinical scenarios are presented.
Phylogenomic Resolution of Sea Spider Diversification through Integration of Multiple Data Classes
Authors: Ballesteros Jesús A , Setton Emily V W , Santibáñez-López Carlos E , Arango Claudia P , Brenneis Georg , Brix Saskia , Corbett Kevin F , Cano-Sánchez Esperanza , Dandouch Merai , Dilly Geoffrey F , Eleaume Marc P , Gainett Guilherme , Gallut Cyril , McAtee Sean , McIntyre Lauren , Moran Amy L , Moran Randy , López-González Pablo J , Scholtz Gerhard , Williamson Clay , Woods H Arthur , Zehms Jakob T , Wheeler Ward C , Sharma Prashant P
Published: September 2020

Despite significant advances in invertebrate phylogenomics over the past decade, the higher-level phylogeny of Pycnogonida (sea spiders) remains elusive. Due to the inaccessibility of some small-bodied lineages, few phylogenetic studies have sampled all sea spider families. Previous efforts based on a handful of genes have yielded unstable tree topologies. Here, we inferred the relationships of 89 sea spider species using targeted capture of the mitochondrial genome, 56 conserved exons, 101 ultraconserved elements, and 3 nuclear ribosomal genes. We inferred molecular divergence times by integrating morphological data for fossil species to calibrate 15 nodes in the arthropod tree of life. This integration of data classes resolved the basal topology of sea spiders with high support. The enigmatic family Austrodecidae was resolved as the sister group to the remaining Pycnogonida and the small-bodied family Rhynchothoracidae as the sister group of the robust-bodied family Pycnogonidae. Molecular divergence time estimation recovered a basal divergence of crown group sea spiders in the Ordovician. Comparison of diversification dynamics with other marine invertebrate taxa that originated in the Paleozoic suggests that sea spiders and some crustacean groups exhibit resilience to mass extinction episodes, relative to mollusk and echinoderm lineages.