bluuebunny/crossref_metadata_2025 huggingface dataset:
Exclusive generation of orbital angular momentum modes in parity-time symmetry fiber gratings
Authors: Lin Tianying , Liu Ang , Li He , Zhang Xiaopei , Han Hailong , Chen Ze , Wang Liping , Liu Xiaoping , Lv Haibin
Published: April 2019

Orbital angular momentum (OAM) modes in fibers process great potentials in providing, from a higher dimension, extra communication channels to meet the ever-growing bandwidth requirement for modern information infrastructures. Long period fiber gratings are commonly used to generate these modes in fibers by coupling fundamental modes to degenerate higher order modes. In order for the generation process to be selective for a certain OAM mode, careful control of the state of polarization (SOP) is required for input fundamental modes. Here, we propose a non-conventional long period fiber grating with not only longitudinal index modulation but also azimuthal parity-time symmetry index modulation, and by placing this grating system at the parity-time exceptional point, an OAM mode with its topological charge matched to the parity-time modulation could be exclusively excited by using any fundamental modes with an arbitrary SOP except for the particular SOP with exactly opposite helicity. Our concept demonstrated here to generate OAM modes in fibers may open up promising applications in parity-time OAM-fiber optics.
A scalable real-time framework for Thomson scattering analysis: Application to NSTX-U
Authors: Laggner F. M. , Diallo A. , LeBlanc B. P. , Rozenblat R. , Tchilinguirian G. , Kolemen E. ,   NSTX-U Team
Published: April 2019

A detailed description of a prototype setup for real-time (RT) Thomson scattering (TS) analysis is presented and implemented in the multi-point Thomson scattering (MPTS) diagnostic system at the National Spherical Torus Experiment Upgrade (NSTX-U). The data acquisition hardware was upgraded with RT capable electronics (RT-analog digital converters and a RT server) that allow for fast digitization of the laser pulse signal of eight radial MPTS channels. In addition, a new TS spectrum analysis software for a rapid calculation of electron temperature (Te) and electron density (ne) was developed. Testing of the RT hardware and data analysis software was successfully completed and benchmarked against the standard, post-shot evaluation. Timing tests were performed showing that the end-to-end processing time was reproducibly below 17 ms for the duration of at least 5 s, meeting a 60 Hz deadline by the laser pulse repetition rate over the length of a NSTX-U discharge. The presented RT framework is designed to be scalable in system size, i.e., incorporation of additional radial channels by solely adding additional RT capable hardware. Furthermore, it is scalable in its operation duration and was continuously running for up to 30 min, making it an attractive solution for machines with long discharges such as advanced, non-inductive tokamaks or stellarators.
Electrostatic capacitance-type acceleration of ions with an intense few-cycle laser pulse
Authors: Shen X. F. , Qiao B. , Zhang H. , Xie Y. , Kar S. , Borghesi M. , Zepf M. , Zhou C. T. , Zhu S. P. , He X. T.
Published: April 2019

We use large scale, three-dimensional particle-in-cell simulations to demonstrate that a high-quality energetic ion beam can be stably generated by irradiation of a multi-species nanofoil target with an intense few-cycle laser pulse. In this scheme named “electrostatic capacitance-type acceleration,” the light ions of the nanofoil are accelerated by a uniform capacitor-like electrostatic field induced by the laser-blown-out electrons that act like the cathode of a capacitor, while the heavy ions left behind serve as the anode. This scheme overcomes the inherent obstacles existing in the other acceleration mechanisms, such as uncontrollability of target normal sheath acceleration and instability of radiation pressure acceleration. Theoretical studies and three-dimensional particle-in-cell simulations show that this acceleration scheme is much more stable and efficient than the previous ones, by which 100 MeV monoenergetic proton beams (energy spread <10%) can be obtained with a laser energy less than 10 J, and the giga electron volt ones with about 100 J.
Evolution of the male palp morphology of the orb-weaver hunting spider Chorizopes (Araneae : Araneidae) revisited on a new phylogeny of Araneidae, and description of a third species from Madagascar
Authors: Kallal Robert J. , Hormiga Gustavo
Published: April 2019

The genus Chorizopes (Araneae, Araneidae) includes over two dozen species of webless araneids found mainly in the Indomalayan region. They are characterised by a distinctive bulbous carapace and a specialised foraging behaviour: preying on other orb-weavers. Chorizopes casictones, sp. nov. (Araneae, Araneidae) is described based on specimens collected in northern Madagascar. This species represents the third member of Chorizopes known from the island. We conducted a total-evidence analysis based on morphology, behaviour and nucleotide sequence data, including this taxon for the first time. The palpal morphology of the male of Chorizopes is illustrated in detail. We discuss the palpal homologies and the evolution of araneid palpal sclerites based on the newly inferred family phylogenetic tree.
Rotational grazing management achieves similar plant diversity outcomes to areas managed for conservation in a semi-arid rangeland
Authors: McDonald Sarah E. , Reid Nick , Smith Rhiannon , Waters Cathleen M. , Hunter John , Rader Romina
Published: April 2019

Despite the increasing extent of protected areas throughout the world, biodiversity decline continues. Grazing management that promotes both biodiversity and production outcomes has the potential to improve broad-scale conservation and complement the protected area network. In this study we explored the potential to integrate commercial livestock grazing and conservation in a semi-arid rangeland in south-eastern Australia. Understorey floristic composition and diversity were compared at different spatial scales across three grazing management treatments: (1) continuous commercial grazing management where paddocks were grazed for the majority of the year (≥8 months per annum); (2) rotational commercial grazing management where livestock are frequently rotated and paddocks rested for >4 months per annum; and (3) protected areas managed for conservation with domestic livestock excluded and grazed only by native and feral herbivores. The season of sampling, rainfall, soil characteristics and the spatial location of sites were the dominant drivers of variability in understorey plant species composition; the effect of grazing treatment on understorey plant species composition was relatively minor. However, areas managed for conservation and under rotational forms of commercial grazing management generally had greater floristic richness and diversity than continuously grazed areas, the results varying with season (spring/autumn) and soil type (clay/sandy-loam), particularly at fine scale (1-m2 quadrats). These findings indicate that rotational grazing management on commercial properties has the potential to improve biodiversity conservation outside the reserve system compared to conventional grazing management.
Parental divorce is not uniformly disruptive to children’s educational attainment
Authors: Brand Jennie E. , Moore Ravaris , Song Xi , Xie Yu
Published: April 2019

Significance

While parental divorce is generally associated with unfavorable outcomes for children, it does not follow that every divorce is equally bad for the children it affected. We find that parental divorce lowers the educational attainment of children who have a low likelihood of their parents’ divorcing. For these children, divorce is an unexpected shock to an otherwise-privileged childhood. However, we find no impact of parents’ divorcing on the education of children who have a high likelihood of a divorce occurring. Disadvantaged children of high-risk marriages may anticipate or otherwise accommodate to the dissolution of their parents’ marriage. Social discourse and policy aimed at promoting marital stability among disadvantaged families, for whom unfortunate events are common, are misguided.
Prediction of positron emitter distributions for range monitoring in carbon ion therapy: an analytical approach
Authors: Hofmann T , Fochi A , Parodi K , Pinto M
Published: April 2019

Range verification is one of the most relevant tasks in ion beam therapy. In the case of carbon ion therapy, positron emission tomography (PET) is the most widely used method for this purpose, which images the

-activation following nuclear interactions of the ions with the tissue nuclei. Since the positron emitter activity profile is not directly proportional to the dose distribution, until today only its comparison to a prediction of the PET profile allows for treatment verification. Usually, this prediction is obtained from time-consuming Monte Carlo simulations of high computational effort, which impacts the clinical workflow. To solve this issue in proton therapy, a convolution approach was suggested to predict positron emitter activity profiles from depth dose distributions analytically. In this work, we introduce an approach to predict positron emitter distributions from depth dose profiles in carbon ion therapy. While the distal fall-off position of the positron emitter profile is predicted from a convolution approach similar to the one suggested for protons, additional analytical functions are introduced to describe the characteristics of the positron emitter distribution in tissue. The feasibility of this approach is demonstrated with monoenergetic depth dose profiles and spread out Bragg peaks in homogeneous and heterogeneous phantoms. In all cases, the positron emitter profile is predicted with high precision and the distal fall-off position is reproduced with millimeter accuracy.
Optimizing wetland restoration to improve water quality at a regional scale
Authors: Singh Nitin K , Gourevitch Jesse D , Wemple Beverley C , Watson Keri B , Rizzo Donna M , Polasky Stephen , Ricketts Taylor H
Published: April 2019

Excessive phosphorus (P) export to aquatic ecosystems can lead to impaired water quality. There is a growing interest among watershed managers in using restored wetlands to retain P from agricultural landscapes and improve water quality. We develop a novel framework for prioritizing wetland restoration at a regional scale. The framework uses an ecosystem service model and an optimization algorithm that maximizes P reduction for given levels of restoration cost. Applying our framework in the Lake Champlain Basin, we find that wetland restoration can reduce P export by 2.6% for a budget of $50 M and 5.1% for a budget of $200 M. Sensitivity analysis shows that using finer spatial resolution data for P sources results in twice the P reduction benefits at a similar cost by capturing hot-spots on the landscape. We identify 890 wetlands that occur in more than 75% of all optimal scenarios and represent priorities for restoration. Most of these wetlands are smaller than 7 ha with contributing area less than 100 ha and are located within 200 m of streams. Our approach provides a simple yet robust tool for targeting restoration efforts at regional scales and is readily adaptable to other restoration strategies.
The Erdős conjecture for primitive sets
Authors: Lichtman Jared , Pomerance Carl
Published: April 2019

A subset of the integers larger than 1 is primitive if no member divides another. Erdős proved in 1935 that the sum of

1

/

(
a
log
⁡
a
)

1/(a\log a)

for

a
a

running over a primitive set

A
A

is universally bounded over all choices for

A
A

. In 1988 he asked if this universal bound is attained for the set of prime numbers. In this paper we make some progress on several fronts and show a connection to certain prime number “races” such as the race between

π
(
x
)

\pi (x)

and

l
i

(
x
)

\mathrm {li}(x)

.
Pathwise integration and change of variable formulas for continuous paths with arbitrary regularity
Authors: Cont Rama , Perkowski Nicolas
Published: April 2019

We construct a pathwise integration theory, associated with a change of variable formula, for smooth functionals of continuous paths with arbitrary regularity defined in terms of the notion of

p
p

th variation along a sequence of time partitions. For paths with finite

p
p

th variation along a sequence of time partitions, we derive a change of variable formula for

p
p

times continuously differentiable functions and show pointwise convergence of appropriately defined compensated Riemann sums.

Results for functions are extended to regular path-dependent functionals using the concept of vertical derivative of a functional. We show that the pathwise integral satisfies an “isometry” formula in terms of

p
p

th order variation and obtain a “signal plus noise” decomposition for regular functionals of paths with strictly increasing

p
p

th variation. For less regular (

C

p
−
1

C^{p-1}

) functions we obtain a Tanaka-type change of variable formula using an appropriately defined notion of local time.

These results extend to multidimensional paths and yield a natural higher-order extension of the concept of “reduced rough path”. We show that, while our integral coincides with a rough path integral for a certain rough path, its construction is canonical and does not involve the specification of any rough-path superstructure.
The rational hull of Rudin’s Klein bottle
Authors: Anderson John , Gupta Purvi , Stout Edgar
Published: April 2019

In this note, a general result for determining the rational hulls of fibered sets in

C

2

\mathbb {C}^2

is established. We use this to compute the rational hull of Rudin’s Klein bottle, the first explicit example of a totally real nonorientable surface in

C

2

\mathbb {C}^2

. In contrast to its polynomial hull, which was shown to contain an open set by the first author in 2012, its rational hull is shown to be

2
2

-dimensional. Using the same method, we also compute the rational hulls of some other surfaces in

C

2

\mathbb {C}^2

.
On the ground state solution of a fractional Schrödinger equation
Authors: Paul S. , Santra Sanjiban
Published: April 2019

In this paper, we discuss the asymptotic behavior of the ground state solution for a fractional Schrödinger equation with a polynomial nonlinearity in one dimension.
Ekeland variational principle on weighted graphs
Authors: Alfuraidan Monther , Khamsi Mohamed
Published: April 2019

In this work, we give a graphical version of the Ekeland variational principle which enables us to discover a new version of the Caristi fixed point theorem in weighted digraphs not necessarily generated by a partial order. Then we show that both graphical versions of the Ekeland variational principle and Caristi’s fixed point theorem are equivalent. In addition, we applied our main result on a differential structure Banach space.
On the asymptotic behavior of solutions to the Benjamin-Ono equation
Authors: Muñoz Claudio , Ponce Gustavo
Published: April 2019

We prove that the limit infimum, as time

t

\,t\,

goes to infinity, of any uniformly bounded in time

H
1

∩

L
1

H^1\cap L^1

solution to the Benjamin-Ono equation converge to zero locally in an increasing in time region of space of order

t

/

log
⁡
t

\,t/\log t

. Also for a solution with a mild

L
1

L^1

-norm growth in time, its limit infimum must converge to zero, as time goes to infinity, locally in an increasing on time region of space of order depending of the rate of growth of its

L
1

L^1

-norm. In particular, we discard the existence of breathers and other solutions for the BO model moving with a speed “slower” than a soliton.
Associating geometry to the Lie superalgebra 𝔰𝔩(1|1) and to the color Lie algebra 𝔰𝔩^{𝔠}₂(\Bbbk)
Authors: Sierra Susan , Špenko Špela , Vancliff Michaela , Veerapen Padmini , Wiesner Emilie
Published: April 2019

In the 1990s, in work of Le Bruyn and Smith and in work of Le Bruyn and Van den Bergh, it was proved that point modules and line modules over the homogenization of the universal enveloping algebra of a finite-dimensional Lie algebra describe useful data associated to the Lie algebra. In particular, in the case of the Lie algebra

s
l

2

(

C

)

\mathfrak {sl}_2(\mathbb {C})

, there is a correspondence between Verma modules and certain line modules that associates a pair

(

h

,

ϕ
)

(\mathfrak {h},\,\phi )

, where

h

\mathfrak {h}

is a

2
2

-dimensional Lie subalgebra of

s
l

2

(

C

)

\mathfrak {sl}_2(\mathbb {C})

and

ϕ
∈

h

∗

\phi \in \mathfrak {h}^*

satisfies

ϕ
(
[

h

,

h

]
)
=
0

\phi ([\mathfrak {h}, \, \mathfrak {h}]) = 0

, to a particular type of line module. In this article, we prove analogous results for the Lie superalgebra

s
l

(
1

|

1
)

\mathfrak {sl}(1|1)

and for a color Lie algebra associated to the Lie algebra

s
l

2

\mathfrak {sl}_2

.
First extremal point comparison for a fractional boundary value problem with a fractional boundary condition
Authors: Henderson Johnny , Neugebauer Jeffrey
Published: April 2019

Let

n
≥
2

n \geq 2

be a natural number, and let

n
−
1
>
α
≤
n

n-1>\alpha \le n

and

0
>
γ
≤
α
−
1

0>\gamma \le \alpha -1

be real numbers. Let

β
>
0

\beta >0

and

b
∈
(
0
,
β
]

b\in (0,\beta ]

. We compare first extremal points of the differential equations

D

0
+

α

u
+
p
(
t
)
u
=
0

D_{0+}^\alpha u+p(t)u=0

,

D

0
+

α

u
+
q
(
t
)
u
=
0

D_{0+}^\alpha u+q(t)u=0

,

t
∈
(
0
,
β
)

t\in (0,\beta )

, each of which satisfies the boundary conditions

u

(
i
)

(
0
)
=
0

u^{(i)}(0)=0

,

i
=
0
,
1
,
…
,
n
−
2

i=0,1,\dots ,n-2

,

D

0
+

γ

u
(
b
)
=
0

\quad D_{0^+}^\gamma u(b)=0

. While it is assumed that

q
q

is nonnegative, no sign restrictions are put on

p
p

. The fact that the associated Green’s function

G
(
b
;
t
,
s
)

G(b;t,s)

is nonnegative and increasing with respect to

b
b

plays an important role in the analysis.
Hindman-like theorems with uncountably many colours and finite monochromatic sets
Authors: Fernández-Bretón David , Lee Sung
Published: April 2019

A particular case of the Hindman–Galvin–Glazer theorem states that, for every partition of an infinite abelian group

G
G

into two cells, there will be an infinite

X
⊆
G

X\subseteq G

such that the set of its finite sums

{

x
1

+
⋯
+

x
n

∣
n
∈

N

∧

x
1

,
…
,

x
n

∈
X
 are distinct
}

\{x_1+\cdots +x_n \mid n\in \mathbb N\wedge x_1,\ldots ,x_n\in X\text { are distinct}\}

is monochromatic. It is known that the same statement is false, in a very strong sense, if one attempts to obtain an uncountable (rather than just infinite)

X
X

. On the other hand, a recent result of Komjáth states that, for partitions into uncountably many cells, it is possible to obtain monochromatic sets of the form

F
S

(
X
)

\mathrm {FS}(X)

, for

X
X

of some prescribed finite size, when working with sufficiently large Boolean groups. In this paper, we provide a generalization of Komjáth’s result, and we show that, in a sense, this generalization is the strongest possible.
A nonisoparametric hypersurface with constant principal curvatures
Authors: Rodríguez-Vázquez Alberto
Published: April 2019

In this note we construct an explicit example of a (compact) conformally flat Riemannian manifold which admits a totally geodesic foliation of codimension one with no isoparametric leaves. This answers negatively the question: Is every hypersurface with constant principal curvatures isoparametric?
Effective cycles on the symmetric product of a curve, I: the diagonal cone
Authors: Bastianelli Francesco , Kouvidakis Alexis , Lopez Angelo , Viviani Filippo
Published: April 2019

In this paper we investigate the cone

Pseff
n

⁡
(

C
d

)

\operatorname {Pseff}_n(C_d)

of pseudoeffective

n
n

-cycles in the symmetric product

C
d

C_d

of a smooth curve

C
C

. We study the convex-geometric properties of the cone

D

n

(

C
d

)

\mathcal {D}_n(C_d)

generated by the

n
n

-dimensional diagonal cycles. In particular we determine its extremal rays and we prove that

D

n

(

C
d

)

\mathcal {D}_n(C_d)

is a perfect face of

Pseff
n

⁡
(

C
d

)

\operatorname {Pseff}_n(C_d)

along which

Pseff
n

⁡
(

C
d

)

\operatorname {Pseff}_n(C_d)

is locally finitely generated.
Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays
Authors: Cook Brian D. , Chang Fred , Flor-Parra Ignacio , Al-Bassam Jawdat
Published: April 2019

XMAP215/Stu2/Alp14 accelerates tubulin polymerization while processively tracking microtubule (MT) plus ends via tumor overexpressed gene (TOG) domain arrays. It remains poorly understood how these functions arise from tubulin recruitment, mediated by the distinct TOG1 and TOG2 domains, or the assembly of these arrays into large square complexes. Here, we describe a relationship between MT plus-end tracking and polymerase functions revealing their distinct origin within TOG arrays. We study Alp14 mutants designed based on structural models, with defects in either tubulin recruitment or self-organization. Using in vivo live imaging in fission yeast and in vitro MT dynamics assays, we show that tubulins recruited by TOG1 and TOG2 serve concerted, yet distinct, roles in MT plus-end tracking and polymerase functions. TOG1 is critical for processive plus-end tracking, whereas TOG2 is critical for accelerating tubulin polymerization. Inactivating interfaces that stabilize square complexes lead to defects in both processive MT plus-end tracking and polymerase. Our studies suggest that a dynamic cycle between square and unfurled TOG array states gives rise to processive polymerase activity at MT plus ends.
Resistant syndrome of inappropriate antidiuretic hormone (SIADH) secondary to atonic bladder in an older woman
Authors: Hogan Patrick C P , McGauran Jane , O’Brien Helen , Rolston Amy , O’Neill Desmond
Published: April 2019

Syndrome of inappropriate antidiuretic hormone (SIADH) is the most common cause of hyponatraemia. There are many causes of SIADH, but investigation tends to focus around the most common causes—particularly diseases of the brain and lung, malignancy and medication-induced SIADH [Ellison and Berl (2007, The Syndrome of Inappropriate Antidiuresis. N Engl J Med., 356, 2064–72]. We describe a case of SIADH secondary to atonic bladder in an 83-year old woman, which was discovered on MRI of the abdomen, performed for further characterisation of a known pancreatic lesion. Insertion of a urinary catheter alleviated retention and resulted in prompt resolution of hyponatraemia. This is an under-recognised cause of this common condition, with important implications for investigation and management.
Graph-based data integration from bioactive peptide databases of pharmaceutical interest: toward an organized collection enabling visual network analysis
Authors: Aguilera-Mendoza Longendri , Marrero-Ponce Yovani , Beltran Jesus A , Tellez Ibarra Roberto , Guillen-Ramirez Hugo A , Brizuela Carlos A
Published: April 2019

Motivation

Bioactive peptides have gained great attention in the academy and pharmaceutical industry since they play an important role in human health. However, the increasing number of bioactive peptide databases is causing the problem of data redundancy and duplicated efforts. Even worse is the fact that the available data is non-standardized and often dirty with data entry errors. Therefore, there is a need for a unified view that enables a more comprehensive analysis of the information on this topic residing at different sites.

Results

After collecting web pages from a large variety of bioactive peptide databases, we organized the web content into an integrated graph database (starPepDB) that holds a total of 71 310 nodes and 348 505 relationships. In this graph structure, there are 45 120 nodes representing peptides, and the rest of the nodes are connected to peptides for describing metadata. Additionally, to facilitate a better understanding of the integrated data, a software tool (starPep toolbox) has been developed for supporting visual network analysis in a user-friendly way; providing several functionalities such as peptide retrieval and filtering, network construction and visualization, interactive exploration and exporting data options.

Availability and implementation

Both starPepDB and starPep toolbox are freely available at http://mobiosd-hub.com/starpep/.

Supplementary information

Supplementary data are available at Bioinformatics online.
A new statistic for efficient detection of repetitive sequences
Authors: Chen Sijie , Chen Yixin , Sun Fengzhu , Waterman Michael S , Zhang Xuegong
Published: April 2019

Motivation

Detecting sequences containing repetitive regions is a basic bioinformatics task with many applications. Several methods have been developed for various types of repeat detection tasks. An efficient generic method for detecting most types of repetitive sequences is still desirable. Inspired by the excellent properties and successful applications of the D2 family of statistics in comparative analyses of genomic sequences, we developed a new statistic D2R that can efficiently discriminate sequences with or without repetitive regions.

Results

Using the statistic, we developed an algorithm of linear time and space complexity for detecting most types of repetitive sequences in multiple scenarios, including finding candidate clustered regularly interspaced short palindromic repeats regions from bacterial genomic or metagenomics sequences. Simulation and real data experiments show that the method works well on both assembled sequences and unassembled short reads.

Availability and implementation

The codes are available at https://github.com/XuegongLab/D2R_codes under GPL 3.0 license.

Supplementary information

Supplementary data are available at Bioinformatics online.
Automatic curation of large comparative animal MicroRNA datasets
Authors: Yazbeck Ali M , Stadler Peter F , Tout Kifah , Fallmann Jörg
Published: April 2019

Motivation

MicroRNAs form an important class of RNA regulators that has been studied extensively. The miRBase and Rfam database provide rich, frequently updated information on both pre-miRNAs and their mature forms. These data sources, however, rely on individual data submission and thus are neither complete nor consistent in their coverage across different miRNA families. Quantitative studies of miRNA evolution therefore are difficult or impossible on this basis.

Results

We present here a workflow and a corresponding implementation, MIRfix, that automatically curates miRNA datasets by improving alignments of their precursors, the consistency of the annotation of mature miR and miR* sequence, and the phylogenetic coverage. MIRfix produces alignments that are comparable across families and sets the stage for improved homology search as well as quantitative analyses.

Availability and implementation

MIRfix can be downloaded from https://github.com/Bierinformatik/MIRfix.

Supplementary information

Supplementary data are available at Bioinformatics online.
New perspective on conceptus estrogens in maternal recognition and pregnancy establishment in the pig†
Authors: Meyer Ashley E , Pfeiffer Caroline A , Brooks Kelsey E , Spate Lee D , Benne Joshua A , Cecil Raissa , Samuel Melissa S , Murphy Clifton N , Behura Susanta , McLean Megan K , Ciernia Lauren A , Smith Michael F , Whitworth Kristin M , Wells Kevin D , Spencer Thomas E , Prather Randall S , Geisert Rodney D
Published: April 2019

The proposed signal for maternal recognition of pregnancy in pigs is estrogen (E2), produced by the elongating conceptuses between days 11 to 12 of pregnancy with a more sustained increase during conceptus attachment and placental development on days 15 to 30. To understand the role of E2 in porcine conceptus elongation and pregnancy establishment, a loss-of-function study was conducted by editing aromatase (CYP19A1) using CRISPR/Cas9 technology. Wild-type (CYP19A1+/+) and (CYP19A1−/−) fibroblast cells were used to create embryos through somatic cell nuclear transfer, which were transferred into recipient gilts. Elongated and attaching conceptuses were recovered from gilts containing CYP19A1+/+ or CYP19A1−/− embryos on day 14 and 17 of pregnancy. Total E2 in the uterine flushings of gilts with CYP19A1−/− embryos was lower than recipients containing CYP19A1+/+ embryos with no difference in testosterone, PGF2α, or PGE2 on either day 14 or 17. Despite the loss of conceptus E2 production, CYP19A1−/− conceptuses were capable of maintaining the corpora lutea. However, gilts gestating CYP19A1−/− embryos aborted between days 27 and 31 of gestation. Attempts to rescue the pregnancy of CYP19A1−/− gestating gilts with exogenous E2 failed to maintain pregnancy. However, CYP19A1−/− embryos could be rescued when co-transferred with embryos derived by in vitro fertilization. Endometrial transcriptome analysis revealed that ablation of conceptus E2 resulted in disruption of a number biological pathways. Results demonstrate that intrinsic E2 conceptus production is not essential for pre-implantation development, conceptus elongation, and early CL maintenance, but is essential for maintenance of pregnancy beyond 30 days .
Life-Course Contribution of Prenatal Stress in Regulating the Neural Modulation Network Underlying the Prepulse Inhibition of the Acoustic Startle Reflex in Male Alzheimer’s Disease Mice
Authors: Jafari Zahra , Kolb Bryan E , Mohajerani Majid H
Published: April 2019

The prepulse inhibition (PPI) of the acoustic startle reflex (ASR), as an index of sensorimotor gating, is one of the most extensively used paradigms in the field of neuropsychiatric disorders. Few studies have examined how prenatal stress (PS) regulates the sensorimotor gating during the lifespan and how PS modifies the development of amyloid-beta (Aβ) pathology in brain areas underlying the PPI formation. We followed alternations in corticosterone levels, learning and memory, and the PPI of the ASR measures in APPNL-G-F/NL-G-F offspring of dams exposed to gestational noise stress. In-depth quantifications of the Aβ plaque accumulation were also performed at 6 months. The results indicated an age-dependent deterioration of sensorimotor gating, long-lasting PS-induced abnormalities in PPI magnitudes, as well as deficits in spatial memory. The PS also resulted in a higher Aβ aggregation predominantly in brain areas associated with the PPI modulation network. The findings suggest the contribution of a PS-induced hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in regulating the PPI modulation substrates leading to the abnormal development of the neural protection system in response to disruptive stimuli. The long-lasting HPA axis dysregulation appears to be the major underlying mechanism in precipitating the Aβ deposition, especially in brain areas contributed to the PPI modulation network.
Tuberculosis in Older Adults: Seattle and King County, Washington
Authors: Gardner Toren Katelynne , Spitters Christopher , Pecha Monica , Bhattarai Sanju , Horne David J , Narita Masahiro
Published: April 2019

Background

In the United States, tuberculosis (TB) incidence rates are highest among adults aged ≥65 years. We performed this study to evaluate outcomes of older patients undergoing treatment for TB disease, including the frequency of adverse events related to TB treatment.

Methods

This study evaluated adult patients who were diagnosed with pulmonary TB from 2009 to 2014 in King County, Washington. Patient characteristics, manifestation of TB, and treatment outcomes in different age groups were compared. Frequency and type of adverse events that resulted in treatment interruption were evaluated and patients aged ≥65 years were compared with selected younger patients.

Results

There were 403 patients who met the study criteria, 111 of whom were aged ≥65 years. Older patients were significantly less likely to have cavitation on chest radiographs. Patients aged ≥65 years were less likely to complete TB treatment (76.6% vs 94.9%, P < .0001) and were more likely to die during treatment (18.9% vs 2.1%, P < .0001). The difference in these outcomes was heightened for those aged ≥75 years compared with those aged <75 years. Those aged ≥75 years were also more likely to have an adverse event attributable to TB medication and were more likely to have an adverse event later in therapy. Regardless of age, pyrazinamide was responsible for the majority of adverse reactions.

Conclusions

Adults aged ≥65 years with pulmonary TB had less-advanced disease but a higher risk of complications during treatment such as death or adverse events. This effect was most pronounced among those aged ≥75 years.
Five non-mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes phenotype adult patients with m.3243A>G mutation after kidney transplantation: follow-up and review of the literature
Authors: de Laat Paul , van Engelen Nienke , Wetzels Jack F , Smeitink Jan A M , Janssen Mirian C H
Published: April 2019

Background

Renal involvement in patients with the m.3243A>G mutation may result in end-stage renal disease (ESRD) requiring renal replacement therapy. Although kidney transplantations have been performed in a small number of patients, short- and long-term follow-up data are lacking.

Methods

We describe five patients with the m.3243AG carriers described in the literature.

Results

Proteinuria with or without renal failure was the first clinical presentation of renal involvement in 13 of 18 (72%) patients. Focal segmental glomerulosclerosis (FSGS) was found in 9 of 13 (69%) biopsies. Sixteen of 18 (84%) patients developed hearing loss. All patients were diagnosed with diabetes mellitus, of whom eight (44%) developed the disease after transplantation. All patients with reported follow-up data (13/18) had stable kidney function from 6 months to 13 years of follow-up after transplantation.

Conclusions

Renal involvement in carriers of the m.3243A>G mutation most commonly leads to proteinuria and FSGS and may lead to ESRD. Proper recognition of the mitochondrial origin of the renal disease in these patients is important for adequate treatment selection and suitable supportive care. This case series and review of the available literature on long-term follow-up after kidney transplantation shows it is feasible for non-mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes phenotype carriers of the m.3243A>G mutation to be considered for kidney transplantation in case of ESRD. These patients should not be excluded from transplant solely for their mitochondrial diagnosis.
A new expression of immune checkpoint inhibitors’ renal toxicity: when distal tubular acidosis precedes creatinine elevation
Authors: Charmetant Xavier , Teuma Cécile , Lake Jennifer , Dijoud Frédérique , Frochot Vincent , Deeb Abbas
Published: April 2019

The main manifestation of acute interstitial nephritis (AIN) due to immune checkpoint inhibitors is acute kidney injury. We report here a biopsy-proven AIN revealed by tubular acidosis. This case highlights that immune checkpoint inhibitor prescribers must be aware of electrolytic disorders since tubular dysfunction can precede serum creatinine increase and reveal renal toxicity.
Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease
Authors: Chaparro M , Garre A , Guerra Veloz M F , Vázquez Morón J M , De Castro M L , Leo E , Rodriguez E , Carbajo A Y , Riestra S , Jiménez I , Calvet X , Bujanda L , Rivero M , Gomollón F , Benítez J M , Bermejo F , Alcaide N , Gutiérrez A , Mañosa M , Iborra M , Lorente R , Rojas-Feria M , Barreiro-de Acosta M , Kolle L , Van Domselaar M , Amo V , Argüelles F , Ramírez E , Morell A , Bernardo D , Gisbert J P
Published: April 2019

Background and Aims

To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®.

Methods

Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The ‘switch cohort’ [SC] comprised patients who made the switch from Remicade® to CT-P13, and the ‘non-switch’ cohort [NC] patients remained under Remicade®.

Results

A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2–6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05].

Conclusions

Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.
Anti-inflammatory Gut Microbial Pathways Are Decreased During Crohn’s Disease Exacerbations
Authors: Klaassen Marjolein A Y , Imhann Floris , Collij Valerie , Fu Jingyuan , Wijmenga Cisca , Zhernakova Alexandra , Dijkstra Gerard , Festen Eleonora A M , Gacesa Ranko , Vich Vila Arnau , Weersma Rinse K
Published: April 2019

Background and Aims

Crohn’s disease [CD] is a chronic inflammatory disorder of the gastrointestinal tract characterised by alternating periods of exacerbation and remission. We hypothesised that changes in the gut microbiome are associated with CD exacerbations, and therefore aimed to correlate multiple gut microbiome features to CD disease activity.

Methods

Faecal microbiome data generated using whole-genome metagenomic shotgun sequencing of 196 CD patients were of obtained from the 1000IBD cohort [one sample per patient]. Patient disease activity status at time of sampling was determined by re-assessing clinical records 3 years after faecal sample production. Faecal samples were designated as taken ‘in an exacerbation’ or ‘in remission’. Samples taken ‘in remission’ were further categorised as ‘before the next exacerbation’ or ‘after the last exacerbation’, based on the exacerbation closest in time to the faecal production date. CD activity was correlated with gut microbial composition and predicted functional pathways via logistic regressions using MaAsLin software.

Results

In total, 105 bacterial pathways were decreased during CD exacerbation (false-discovery rate [FDR] <0.1) in comparison with the gut microbiome of patients both before and after an exacerbation. Most of these decreased pathways exert anti-inflammatory properties facilitating the biosynthesis and fermentation of various amino acids [tryptophan, methionine, and arginine], vitamins [riboflavin and thiamine], and short-chain fatty acids [SCFAs].

Conclusions

CD exacerbations are associated with a decrease in microbial genes involved in the biosynthesis of the anti-inflammatory mediators riboflavin, thiamine, and folate, and SCFAs, suggesting that increasing the intestinal abundances of these mediators might provide new treatment opportunities. These results were generated using bioinformatic analyses of cross-sectional data and need to be replicated using time-series and wet lab experiments.
Antegrade selective cerebral perfusion reduced in-hospital mortality and permanent focal neurological deficit in patients with elective aortic arch surgery†
Authors: Leontyev Sergey , Davierwala Piroze M , Semenov Mikhail , von Aspern Konstantin , Krog Gunter , Noack Thilo , Misfeld Martin , Borger Michael A
Published: April 2019

OBJECTIVES

We retrospectively evaluated the outcome after elective aortic arch surgery with circulatory arrest to determine the impact of different brain protection strategies on neurological outcome and early and late survival.

METHODS

A total of 925 patients were included. The patients were assigned to 2 groups based on the type of cerebral protection strategy used during circulatory arrest [hypothermic circulatory arrest (HCA) n = 224; antegrade selective cerebral perfusion (ASCP) n = 701]. The propensity score matching (1:1; 210 vs 210 patients) approach was used to minimize selection bias and to obtain comparable groups.

RESULTS

The overall in-hospital mortality and permanent focal neurological deficit rates were 5.6% (n = 52) and 5.4% (n = 50) and were significantly lower in patients who received ASCP (4.4% and 3.4%, respectively) as compared to those who underwent HCA (9.4% and 11.6%, respectively) (P = 0.005 and P < 0.001). The propensity-matched analysis showed significantly lower rates of in-hospital mortality [3.8% vs 9.5% (HCA)] and permanent focal neurological deficit in ASCP group [2.9% vs 11.9% (HCA)]. Multivariable logistic regression analysis revealed left ventricular ejection fraction <30%, age >70 years, coronary artery disease, circulatory arrest time >40 min and mitral valve disease as independent predictors of in-hospital mortality. The use of ASCP was protective for early survival. Cox regression analysis revealed that long-term mortality was independently predicted by age, left ventricular ejection fraction <30%, total arch replacement, prior cardiac surgery, PVD, chronic obstructive pulmonary disease and previous stroke, whereas ASCP was protective for late survival.

CONCLUSIONS

Elective aortic arch surgery is associated with acceptable early and late outcomes. The ASCP is associated with a significant reduction in-hospital mortality and occurrence of permanent neurological deficits.
Association between sense of coherence and dental caries: systematic review and meta-analysis
Authors: Torres Thaís Ariane Perdigão , Corradi-Dias Larissa , Oliveira Patrícia Drummond , Martins Carolina Castro , Paiva Saul Martins , Pordeus Isabela Almeida , Abreu Lucas Guimarães
Published: April 2019

Sense of coherence (SOC) is regarded as the individuals' capacity for managing the stressors over their lifespan. The aim of this systematic review and meta-analysis was to evaluate the association between SOC and dental caries. Electronic searchers were conducted in six databases: PubMed, Medline, Scopus, Web of Science, Lilacs and Proquest from their date of inception until November/2017. An update took place in August/2018. A hand search in the reference list of the included articles and gray literature search were also carried out. Retrieved titles/abstracts were screened by two review authors. Data of the included articles were extracted and quality assessment was also conducted. The first search retrieved 346 titles/abstracts. The update retrieved 33 records. Following the removal of 70 duplicates, 309 references were screened and 17 were included. The quality assessment ranged from low quality articles to high quality articles. High quality study showed that adult individuals with lower SOC were more likely to have dental caries. Meta-analysis showed that adolescents with low SOC were 5.41 times more likely to present dental caries than adolescents with high SOC (CI = 2.15–13.59). Mothers with low SOC were 5.55 times more likely to have children/adolescents with dental caries than mothers with high SOC (CI = 2.92–10.57). The subgroup analysis exploring continuous data showed that the SOC of mothers of children/adolescents without dental caries was significantly higher than the SOC of mothers of children/adolescents with dental caries (CI = 0.10–0.51). Higher levels of SOC seem to be associated with lower levels of dental caries.
Language and framing as determinants of the predominance of behavioural health promotion: an Australian view
Authors: Fry Denise
Published: April 2019

The language used in health promotion warrants attention as it shapes how health promotion is understood, constraining or opening up possibilities for action. The 2016 Shanghai Declaration and the 1986 Ottawa Charter for Health Promotion call for comprehensive approaches which include policy and environmental changes. Yet many health promotion programmes in Australia continue to focus on informational and/or behavioural strategies, and there is a contemporary tendency for such programmes to be described as ‘sending messages’. This paper uses frame analysis to discuss the role of language, and specifically language that frames health promotion as sending messages, in contributing to and reinforcing the predominance of informational and/or behavioural strategies. It argues such ‘message’ language helps to set a pattern in which informational and/or behavioural strategies are assumed to be the primary goal and extent of health promotion; rather than one component of a comprehensive, multi-strategic approach. It discusses how frames can be ‘taken for granted’ and ways in which such frames can be challenged and broadened. It argues that the message frame and associated behavioural framings set narrow boundaries for health promotion, contributing to the continuation of health inequities. These frames can also displace the language of the Ottawa Charter, which has capacity to reframe health issues socio-ecologically and include collective strategies. The paper concludes that a first step (of the many needed) towards applying the Charter’s approach and multi-level, multi-strategic framework is to use the innovative vocabulary it offers. The words matter.
Strong convergence rates for an explicit numerical approximation method for stochastic evolution equations with non-globally Lipschitz continuous nonlinearities
Authors: Jentzen Arnulf , Pušnik Primož
Published: April 2019

In this article we propose a new, explicit and easily implementable numerical method for approximating a class of semilinear stochastic evolution equations with non-globally Lipschitz continuous nonlinearities. We establish strong convergence rates for this approximation method in the case of semilinear stochastic evolution equations with globally monotone coefficients. Our strong convergence result, in particular, applies to a class of stochastic reaction–diffusion partial differential equations.
Characterization of a novel, type II staphylococcal cassette chromosome mec element from an endemic oxacillin-resistant Staphylococcus lugdunensis clone in a hospital setting
Authors: Chang Shih-Cheng , Lin Lee-Chung , Ge Mao-Cheng , Liu Tsui-Ping , Lu Jang-Jih
Published: April 2019

Background

Staphylococcus lugdunensis is a significant pathogen that causes community-acquired and nosocomial infections. The high prevalence of oxacillin-resistant S. lugdunensis (ORSL) is of major concern. Resistance to β-lactams is caused by acquisition of the staphylococcal cassette chromosome mec (SCCmec) element. The cassette is highly diverse, both structurally and genetically, among CoNS. Isolates carrying SCCmec II-ST6 are the major persistent clones in hospitals.

Objectives

To investigate the structure and evolutionary origin of a novel type II SCCmec element in an endemic ST6 S. lugdunensis clone.

Methods

The structure of the SCCmec II element carried by ST6 strain CGMH-SL118 was determined by WGS and compared with those reported previously.

Results

A novel 39 kb SCCmec element, SCCmecCGMH-SL118, with a unique mosaic structure comprising 41 ORFs integrated into the 3′ end of the rlmH gene, was observed. Some regions of SCCmecCGMH-SL118 were homologous to SCCmec IIa of the prototype MRSA strain N315. The structure of SCCmecCGMH-SL118 was similar to that of SCCmec IIb of the MRSA strain, JCSC3063, mainly lacking the aminoglycoside resistance determinant pUB110 in the J3 region but containing the insertion sequence IS256 in the J2 region. Notably, SCCmecCGMH-SL118 deletions in the J1 region compared with SCCmec types IIa and IIb, and a high homology to SCCmec elements of Staphylococcus aureus JCSC4610 and Staphylococcus haemolyticus strain 621 were found.

Conclusions

The genetic diversity of the type II SCCmec element in ORSL suggests that CoNS is a potential reservoir for interspecies transfer of SCCmec to S. aureus in hospitals.