bluuebunny/crossref_metadata_2025 huggingface dataset:
Isorhamnetin, a 3’-methoxylated flavonol, enhances the lysosomal proteolysis in J774.1 murine macrophages in a TFEB-independent manner.
Authors: Sakai Maiko , Ohnishi Kohta , Masuda Masashi , Ohminami Hirokazu , Yamanaka-Okumura Hisami , Hara Taichi , Taketani Yutaka
Published: February 2020

Lysosome is the principal organelle for the ultimate degradation of cellular macromolecules, which are delivered through endocytosis, phagocytosis, and autophagy. The lysosomal functions have been found to be impaired by fatty foods and aging, and more importantly, the lysosomal dysfunction in macrophages has been reported as a risk of atherosclerosis development. In this study, we searched for dietary polyphenols which possess the activity for enhancing the lysosomal degradation in J774.1, a murine macrophage-like cell line. Screening test utilizing DQ-BSA digestion identified isorhamnetin (3ʹ-O-methylquercetin) as an active compound. Interestingly, structural comparison to inactive flavonols revealed that the chemical structure of the B-ring moiety in isorhamnetin is the primary determinant of its lysosome-enhancing activity. Unexpectedly isorhamnetin failed to inhibit mTORC1-TFEB signaling, a master regulator of lysosomal biogenesis and function. Our data suggested that the other molecular mechanism might be critical for the regulation of lysosomes in macrophages.

Abbreviations: ANOVA: analysis of variance; ApoE: apolipoprotein E; ATP6V0D2: ATPase H+ transporting V0 subunit d2; BAF: bafilomycin A1; BODIPY: boron dipyrromethene; BSA: bovine serum albumin; CTSD: cathepsin D; CTSF: cathepsin F; DMEM: Dulbecco’s modified eagle medium; DMSO: dimethyl sulfoxide; EGCG: epigallocatechin-3-gallate; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HPLC: high-performance liquid chromatography; LAMP1: lysosomal-associated membrane protein 1; LAMP2A: lysosomal-associated membrane protein 2A; LC-MS/MS: liquid chromatography tandem mass spectrometry; MITF: microphthalmia-associated transcription factor; MRM: multiple reaction monitoring; mTORC1: mechanistic target of rapamycin complex 1; PBS: phosphate-buffered saline; PPARγ: peroxisome proliferator-activated receptor γ; RT-qPCR: reverse transcription quantitative polymerase chain reaction; SDS: sodium dodecyl sulfate; SNARE: soluble N-ethylmaleimide-sensitive-factor attachment protein receptor; TBS: Tris-buffered saline; TFA: trifluoroacetic acid; TFE3: transcription factor binding to IGHM enhancer 3; TFEB: transcriptional factor EB; TFEC: transcription factor EC; V-ATPase: vacuolar-type proton ATPase.
Metered reagent injection into microfluidic continuous flow sampling for conductimetric ocean dissolved inorganic carbon sensing
Authors: Tweedie Mark , Macquart Antonin , Almeida Joao , Ward Brian , Maguire Paul
Published: February 2020

Continuous autonomous measurement of total dissolved inorganic carbon (TCO2) in the oceans is critical for climate change modelling and ocean acidification measurement. A microfluidic conductivity-based approach will permit integration of miniaturised chemical analysis systems into Argo ocean floats, for long-term, high-accuracy depth profiling of dissolved CO2 with minimal reagent payload. Precise metering, suitable for sample acidification and CO2 liberation, is addressed. Laser etched microfluidic snake channel restrictors and asymmetric Y-meters were fabricated, with channel dimensions down to ∼75 μm, to adjust metering ratios between seawater and acid simulants. Hydrodynamic resistances, from flow versus pressure measurements, were compared with finite element simulations for various cross-section profiles and areas. Microfluidic metering circuits were constructed from various resistance snake channels and Y-junction components. Sample to acid volume ratios (meter ratio) up to 100:1 have been achieved with 300 μm wide snake channels for lengths >m. At highest resolution, the footprint would be >600 mm2. Circuits based solely on asymmetric Y-junctions gave maximum meter ratios of 16:1 with a footprint of <40 mm2 and ∼0.2% precision. Further refinement is required to ensure the integrity of such small channels in integration of metering units into full TCO2 analysis microfluidic circuits.
Design of resonant structures in resin matrix to mitigate the blast wave with a very wide frequency range
Authors: Li Q Q , He Z C , Li E , Liu P , Lin X Y , Wu Y
Published: February 2020

In this work, resonant structures (RSs) are embedded in the resin matrix to form the micro-scale artificial composite materials to mitigate the blast wave with a very wide frequency range (BWR). The propagation of stress waves in the resin and composite materials is described, and the composite materials exhibit stronger blast wave attenuation characteristic compared with the pure resin material. The attenuation mechanism of the composite materials is explained in detail through the absorption, storage and conversion of impact energy. In addition, the influences of materials of the RSs on the performances of the composite materials are analyzed, and the RS is redesigned to further improve the attenuation effect of the composite material. Equivalent model of the composite material is first proposed and established based on the weakly nonlinear lattice system (WNLS). At the same time, artificial tree algorithm is applied to design its spring stiffness parameters. Based on the WNLS, a three-dimensional composite material plate structure is built to mitigate the overpressure of blast wave at the macro-scale. Compared with traditional materials, the composite material exhibits superior attenuation effect and greater lightweight.
Using machine learning to reveal the population vector from EEG signals
Authors: Kobler Reinmar J , Almeida Inês , Sburlea Andreea I , Müller-Putz Gernot R
Published: February 2020

Objective. Since the discovery of the population vector that directly relates neural spiking activity with arm movement direction, it has become feasible to control robotic arms and neuroprostheses using invasively recorded brain signals. For non-invasive approaches, a direct relation between human brain signals and arm movement direction is yet to be established. Approach. Here, we investigated electroencephalographic (EEG) signals in temporal and spectral domains in a continuous, circular arm movement task. Using machine learning methods that respect the linear mixture of brain activity within EEG signals, we show that directional information is represented in the temporal domain in amplitude modulations of the same frequency as the arm movement, and in the spectral domain in power modulations of the 20–24 Hz frequency band. Main results. In the temporal domain, the directional information was mainly expressed in primary sensorimotor cortex (SM1) and posterior parietal cortex (PPC) contralateral to the moving arm, while in the spectral domain SM1 and PPC of both hemispheres predicted arm movement direction. The different cortical representations suggest distinct neural representations in both domains. Significance. This direct relation between neural activity and arm movement direction in both domains demonstrates the potential of machine learning to reveal neuroscientific insights about the dynamics of human arm movements.
A seven-fold rise in the probability of exceeding the observed hottest summer in India in a 2 °C warmer world
Authors: J S Nanditha , van der Wiel Karin , Bhatia Udit , Stone Dáithí , Selton Frank , Mishra Vimal
Published: February 2020

Heatwaves and extreme temperatures during summer (April–May) in India have profound implications on public health, mortality, water availability, and productivity of labourers. However, how the frequency of the hottest summers in observed record (1951–2015) will change under the warming climate in India is not well explored. Using observations from the India Meteorological Department, we show that mean maximum summer temperature has increased significantly in three (arid, monsoon, and savannah) out of five major climatic regions of India during 1951–2015. We identify the hottest summer in the observed record in the five climatic regions in India. The arid, cold, and temperate regions experienced the hottest summer in 2010 while monsoon and Savannah regions witnessed the hottest summer in 1979 and 1973, respectively. Based on simulations from the Climate of 20th Century Plus (C20C+) Detection and Attribution project, we show that the regional hottest summer of 2010 can be attributed to the anthropogenic warming. We then use simulations of a large (2000 year) ensemble of the EC-Earth model to estimate the exceedance probability of the observed hottest summer in the present climate, 2 °C and 3 °C warming worlds in India. The exceedance probability of the observed hottest summers shows a rise of more than seven and twenty-fold in the 2 °C and 3 °C warming world, respectively, compared to the present climate. The projected increases in the frequency of the hot summers and associated heatwave days will pose great societal challenges in the future in India.
Wigner distribution and Boltzmann-Shannon entropy for a diatomic molecule under polarized electric field interaction
Authors: López Gustavo V , Mercado Alejandro P
Published: February 2020

We study the classical chaos appearing in a diatomic molecules BeO, CO and CN due to the interaction with a circularly polarized electric field, and its signature in Quantum Mechanics through the Wigner distribution function and the Boltzmann-Shannon entropy. We found a motion out of the center of the quantum phase space defined by Wigner function when the classical system becomes chaotic, and we found a jumping behavior of the average Boltzmann-Shannon entropy with respect the electric field strength when the classical system becomes chaotic, indicating a sudden increasing in the disorder (or sudden lost of information) in the quantum system.
Subgroups of 𝑆𝐿₂(ℤ) characterized by certain continued fraction representations
Authors: Han Sandie , Masuda Ariane , Singh Satyanand , Thiel Johann
Published: February 2020

For positive integers

u
u

and

v
v

, let

L
u

=

[

1

a
m
p
;
0

u

a
m
p
;
1

]

L_u=\left [\begin {smallmatrix} 1 & 0 \\ u & 1 \end {smallmatrix}\right ]

and

R
v

=

[

1

a
m
p
;
v

0

a
m
p
;
1

]

R_v=\left [\begin {smallmatrix} 1 & v \\ 0 & 1 \end {smallmatrix}\right ]

. Let

S

u
,
v

S_{u,v}

be the monoid generated by

L
u

L_u

and

R
v

R_v

, and let

G

u
,
v

G_{u,v}

be the group generated by

L
u

L_u

and

R
v

R_v

. In this paper we expand on a characterization of matrices

M
=

[

a

a
m
p
;
b

c

a
m
p
;
d

]

M=\left [\begin {smallmatrix}a & b \\c & d\end {smallmatrix}\right ]

in

S

k
,
k

S_{k,k}

and

G

k
,
k

G_{k,k}

when

k
≥
2

k\geq 2

given by Esbelin and Gutan to

S

u
,
v

S_{u,v}

when

u
,
v
≥
2

u,v\geq 2

and

G

u
,
v

G_{u,v}

when

u
,
v
≥
3

u,v\geq 3

. We give a simple algorithmic way of determining if

M
M

is in

G

u
,
v

G_{u,v}

using a recursive function and the short continued fraction representation of

b

/

d

b/d

.
𝐾-stability of continuous 𝐶(𝑋)-algebras
Authors: Seth Apurva , Vaidyanathan Prahlad
Published: February 2020

A C*-algebra is said to be

K
K

-stable if its nonstable

K
K

-groups are naturally isomorphic to the usual

K
K

-theory groups. We study continuous

C
(
X
)

C(X)

-algebras, each of whose fibers are

K
K

-stable. We show that such an algebra is itself

K
K

-stable under the assumption that the underlying space

X
X

is compact, metrizable, and of finite covering dimension.
Turán number of bipartite graphs with no 𝐾_{𝑡,𝑡}
Authors: Sudakov Benny , Tomon István
Published: February 2020

The extremal number of a graph

H
H

, denoted by

ex

(
n
,
H
)

\textrm {ex}(n,H)

, is the maximum number of edges in a graph on

n
n

vertices that does not contain

H
H

. The celebrated Kővári-Sós-Turán theorem says that for a complete bipartite graph with parts of size

t
≤
s

t\leq s

the extremal number is

ex

(

K

s
,
t

)
=
O
(

n

2
−
1

/

t

)

\textrm {ex}(K_{s,t})=O(n^{2-1/t})

. It is also known that this bound is sharp if

s
>
(
t
−
1
)
!

s>(t-1)!

. In this paper, we prove that if

H
H

is a bipartite graph such that all vertices in one of its parts have degree at most

t
t

but

H
H

contains no copy of

K

t
,
t

K_{t,t}

, then

ex

(
n
,
H
)
=
o
(

n

2
−
1

/

t

)

\textrm {ex}(n,H)=o(n^{2-1/t})

. This verifies a conjecture of Conlon, Janzer, and Lee.
The Lane-Emden equation with variable double-phase and multiple regime
Authors: Alves Claudianor , Rădulescu Vicenţiu
Published: February 2020

We are concerned with the study of the Lane-Emden equation with variable exponent and Dirichlet boundary condition. The feature of this paper is that the analysis that we develop does not assume any subcritical hypotheses and the reaction can fulfill a mixed regime (subcritical, critical, and supercritical). We consider the radial and the nonradial cases, as well as a singular setting. The proofs combine variational and analytic methods with a version of the Palais principle of symmetric criticality.
Studies of Differences from the point of view of Nevanlinna Theory
Authors: Jianhua Zheng , Korhonen Risto
Published: February 2020

This paper consists of three parts. First, we give so far the best condition under which the shift invariance of the counting function, and of the characteristic of a subharmonic function, holds. Second, a difference analogue of logarithmic derivative of a

δ
\delta

-subharmonic function is established allowing the case of hyper-order equal to one and minimal hyper-type, which improves the condition of the hyper-order less than one. Finally, we make a careful discussion of a well-known difference equation and give the possible forms of the equation under a growth condition for the solutions.
Noncompact complete Riemannian manifolds with singular continuous spectrum embedded into the essential spectrum of the Laplacian, I. The hyperbolic case
Authors: Jitomirskaya Svetlana , Liu Wencai
Published: February 2020

We construct Riemannian manifolds with singular continuous spectrum embedded in the absolutely continuous spectrum of the Laplacian. Our manifolds are asymptotically hyperbolic with sharp curvature bounds.
scTSSR: gene expression recovery for single-cell RNA sequencing using two-side sparse self-representation
Authors: Jin Ke , Ou-Yang Le , Zhao Xing-Ming , Yan Hong , Zhang Xiao-Fei
Published: February 2020

Motivation

Single-cell RNA sequencing (scRNA-seq) methods make it possible to reveal gene expression patterns at single-cell resolution. Due to technical defects, dropout events in scRNA-seq will add noise to the gene-cell expression matrix and hinder downstream analysis. Therefore, it is important for recovering the true gene expression levels before carrying out downstream analysis.

Results

In this article, we develop an imputation method, called scTSSR, to recover gene expression for scRNA-seq. Unlike most existing methods that impute dropout events by borrowing information across only genes or cells, scTSSR simultaneously leverages information from both similar genes and similar cells using a two-side sparse self-representation model. We demonstrate that scTSSR can effectively capture the Gini coefficients of genes and gene-to-gene correlations observed in single-molecule RNA fluorescence in situ hybridization (smRNA FISH). Down-sampling experiments indicate that scTSSR performs better than existing methods in recovering the true gene expression levels. We also show that scTSSR has a competitive performance in differential expression analysis, cell clustering and cell trajectory inference.

Availability and implementation

The R package is available at https://github.com/Zhangxf-ccnu/scTSSR.

Supplementary information

Supplementary data are available at Bioinformatics online.
Intraepidermal nerve fibre density as biomarker in Charcot–Marie–Tooth disease type 1A
Authors: Hartmannsberger Beate , Doppler Kathrin , Stauber Julia , Schlotter-Weigel Beate , Young Peter , Sereda Michael W , Sommer Claudia
Published: February 2020

Charcot–Marie–Tooth disease type 1A, caused by a duplication of the gene peripheral myelin protein 22 kDa, is the most frequent subtype of hereditary peripheral neuropathy with an estimated prevalence of 1:5000. Patients suffer from sensory deficits, muscle weakness and foot deformities. There is no treatment approved for this disease. Outcome measures in clinical trials were based mainly on clinical features but did not evaluate the actual nerve damage. In our case–control study, we aimed to provide objective and reproducible outcome measures for future clinical trials. We collected skin samples from 48 patients with Charcot–Marie–Tooth type 1A, 7 patients with chronic inflammatory demyelinating polyneuropathy, 16 patients with small fibre neuropathy and 45 healthy controls. To analyse skin innervation, 40-µm cryosections of glabrous skin taken from the lateral index finger were double-labelled by immunofluorescence. The disease severity of patients with Charcot–Marie–Tooth type 1A was assessed by the Charcot–Marie–Tooth neuropathy version 2 score, which ranged from 3 (mild) to 27 (severe) and correlated with age (P < 0.01, R = 0.4). Intraepidermal nerve fibre density was reduced in patients with Charcot–Marie–Tooth type 1A compared with the healthy control group (P < 0.01) and negatively correlated with disease severity (P < 0.05, R = −0.293). Meissner corpuscle (MC) density correlated negatively with age in patients with Charcot–Marie–Tooth type 1A (P < 0.01, R = −0.45) but not in healthy controls (P = 0.07, R = 0.28). The density of Merkel cells was reduced in patients with Charcot–Marie–Tooth type 1A compared with healthy controls (P < 0.05). Furthermore, in patients with Charcot–Marie–Tooth type 1A, the fraction of denervated Merkel cells was highly increased and correlated with age (P < 0.05, R = 0.37). Analysis of nodes of Ranvier revealed shortened paranodes and a reduced fraction of long nodes in patients compared with healthy controls (both P < 0.001). Langerhans cell density was increased in chronic inflammatory demyelinating polyneuropathy, but not different in Charcot–Marie–Tooth type 1A compared with healthy controls. Our data suggest that intraepidermal nerve fibre density might be used as an outcome measure in Charcot–Marie–Tooth type 1A disease, as it correlates with disease severity. The densities of Meissner corpuscles and Merkel cells might be an additional tool for the evaluation of the disease progression. Analysis of follow-up biopsies will clarify the effects of Charcot–Marie–Tooth type 1A disease progression on cutaneous innervation.
Infection-associated Immune Perturbations Resolve 1 Year Following Treatment forLoa loa
Authors: Herrick Jesica A , Makiya Michelle A , Holland-Thomas Nicole , Klion Amy D , Nutman Thomas B
Published: February 2020

Background

We have previously demonstrated that eosinophil-associated processes underlie some of the differences in clinical presentation among patients with Loa loa infection prior to therapy and that some posttreatment adverse events appear to be dependent on eosinophil activation.

Methods

We first conducted a retrospective review of 204 patients (70 microfilaria [MF] positive/134 negative) with Loa loa both before and following definitive therapy. We then measured filarial-specific antibodies, eosinophil- and Th2-associated cytokines, and eosinophil granule proteins in their banked serum prior to and at 1 year following definitive treatment. We also evaluated the influence of pretreatment corticosteroids and/or apheresis in altering the efficacy of treatment.

Results

Patients without circulating microfilariae (MF negative) not only had a higher likelihood of peripheral eosinophilia and increased antifilarial antibody levels but also had significantly increased concentrations of granulocyte-macrophage colony–stimulating factor, interleukin (IL) 5, and IL-4 compared with MF-positive patients. However, these differences had all resolved by 1 year after treatment, when all parameters approached the levels seen in uninfected individuals. Neither pretreatment with corticosteroids nor apheresis reduced the efficacy of the diethylcarbamazine used to treat these subjects.

Conclusions

Our results highlight that, by 1 year following treatment, infection-associated immunologic abnormalities had resolved in nearly all patients treated for loiasis, and pretreatment corticosteroids had no influence on the resolution of the immunologic perturbations nor on the efficacy of diethylcarbamazine as a curative agent in loiasis.

Clinical Trials Registration

NCT00001230.
Analytical Performance Specifications for Lipoprotein(a), Apolipoprotein B-100, and Apolipoprotein A-I Using the Biological Variation Model in the EuBIVAS Population
Authors: Clouet-Foraison Noemie , Marcovina Santica M , Guerra Elena , Aarsand Aasne K , Coşkun Abdurrahman , Díaz-Garzón Jorge , Fernandez-Calle Pilar , Sandberg Sverre , Ceriotti Ferruccio , Carobene Anna
Published: February 2020

Background

With increased interest in lipoprotein(a) (Lp[a]) concentration as a target for risk reduction and growing clinical evidence of its impact on cardiovascular disease (CVD) risk, rigorous analytical performance specifications (APS) and accuracy targets for Lp(a) are required. We investigated the biological variation (BV) of Lp(a), and 2 other major biomarkers of CVD, apolipoprotein A-I (apoA-I) and apolipoprotein B-100 (apoB), in the European Biological Variation Study population.

Method

Serum samples were drawn from 91 healthy individuals for 10 consecutive weeks at 6 European laboratories and analyzed in duplicate on a Roche Cobas 8000 c702. Outlier, homogeneity, and trend analysis were performed, followed by CV-ANOVA to determine BV estimates and their 95% CIs. These estimates were used to calculate APS and reference change values. For Lp(a), BV estimates were determined on normalized concentration quintiles.

Results

Within-subject BV estimates were significantly different between sexes for Lp(a) and between women aged <50 and >50 years for apoA-I and apoB. Lp(a) APS was constant across concentration quintiles and, overall, lower than APS based on currently published data, whereas results were similar for apoA-I and apoB.

Conclusion

Using a fully Biological Variation Data Critical Appraisal Checklist (BIVAC)–compliant protocol, our study data confirm BV estimates of Lp(a) listed in the European Federation of Clinical Chemistry and Laboratory Medicine database and reinforce concerns expressed in recent articles regarding the suitability of older APS recommendations for Lp(a) measurements. Given the heterogeneity of Lp(a), more BIVAC-compliant studies on large numbers of individuals of different ethnic groups would be desirable.
Who Face Me? Neighbor Identification With LED Camera Communication
Authors: Zhang Jianhui , Zhang Tianhao , Jiang Feilong , Zhao Bei
Published: February 2020

Neighbor discovery is a fundamental task to support many other services in wireless multihop networks (WMN). Most existing related methods in WMN rely heavily on the information of radio waves. To extend the way to the neighbor discovery, this paper introduces another interesting way, visual light communication, to explore its property of linear transmission. We apply light emitting diode (LED) array and camera and present a novel communication system, named LED array to camera system (LC). This paper also designs a novel protocol, named LED to camera protocol (LCP), for it. Equipped with an LC, each node in a WMN can determine the precise direction and distance of its neighbors and recognize their identities. Furthermore, this paper also develops a method to infer the topology of the whole network. We design the hardware for LC and conduct extensive experiments to implement the protocol LCP. The average latency of the neighbor discovery is measured and can be as small as 1.087 seconds. LCP can achieve centimeter-level accuracy in distance and direction to averages of 0.37 cm and 1.67 degrees in these real experiments. The relative accuracies in distance and direction measurement are 99.11% and 88.92% on average, respectively. The simulation of the topology inference is also performed to show the feasibility and accuracy with the local distance and direction information.
Sustainability, Ecology, and Agriculture in Women Farmers’ Voices: Culture-Centering Gender and Development
Authors: Dutta Mohan J , Thaker Jagadish
Published: February 2020

The neoliberal/neocolonial transformation of agriculture in the global South is achieved through the hegemony of expert-led interventions of privatization that erase the knowledge of agricultural practices held by subaltern communities. Neocolonial development interventions serve the privatizing logics of agro-capital through the circulation of logics of profits, efficiency, and growth through both paid and state-controlled communication channels. In this backdrop, our ethnographic description of a culture-centered intervention carried out in solidarity with dalit, women farmers organized under the umbrella of sanghams (cooperatives) points toward communication sovereignty as a theoretical anchor for re-imagining the relationships among ecology, agriculture, and sustainability in resistance to capitalist agriculture. Challenging hegemonic models of participatory engagement put forth by neocolonial structures of development, the concept of communicative justice inverts listening, radically placing power in the hands of subaltern communities. Layers of inequalities from households to community spaces to market structures are disrupted through the voices of dalit women farmers and their participation in practices that materially resist capitalist agriculture. Moreover, the co-creative work of generating theory from within subaltern struggles for sovereignty in the global South dislocates the colonial nature of abs/ex-tractive theorizing in the metropole in the North, situating the work of theorizing amidst the lifeworlds of subaltern communities performing everyday transformative practices that dismantle capitalist logics.
Vedolizumab Efficacy, Safety, and Pharmacokinetics With Reduced Frequency of Dosing From Every 4 Weeks to Every 8 Weeks in Patients With Crohn’s Disease or Ulcerative Colitis
Authors: Vermeire Séverine , Lukáš Milan , Magro Fernando , Adsul Shashi , Lindner Dirk , Rosario Maria , Roth Jeannine , Danese Silvio
Published: February 2020

Background and Aims

Vedolizumab was shown to be safe and effective for the treatment of Crohn’s disease [CD] and ulcerative colitis [UC] in the GEMINI Long-Term Safety [LTS] study. The vedolizumab Extended Access Program [XAP] provides patients with continued treatment. This XAP pharmacokinetics [PK] sub-study investigated vedolizumab efficacy, safety, and PK.

Methods

Vedolizumab dosing frequency was reduced from every 4 weeks [Q4W] to every 8 weeks [Q8W] at XAP enrolment, and patients were followed for 56 weeks. Outcomes included: efficacy, loss of clinical benefit, and re-escalation to Q4W dosing; and vedolizumab PK, immunogenicity, and adverse events.

Results

Among 167 enrolled patients [CD = 88, UC = 79], 80 [91%] with CD and 73 [92%] with UC completed 56 weeks; 76 [86%] and 71 [90%] with CD and UC, respectively, remained on Q8W dosing for 56 weeks. Clinical remission, corticosteroid-free clinical remission, and C-reactive protein levels were stable among patients remaining on Q8W through Week 56. Four patients with CD and two with UC resumed Q4W dosing [three with CD regained clinical response]. Patients with CD who completed Week 56 on Q8W dosing had median trough vedolizumab concentrations of 43.6 µg/mL at enrolment and 10.4 µg/mL at Week 56; concentrations were 42.4 µg/mL and 13.3 µg/mL, respectively, in patients with UC. Treatment-related adverse events were infrequent; no new or serious adverse events related to vedolizumab were reported.

Conclusions

In the XAP-PK sub-study, adherence to Q8W dosing was high, with no loss of efficacy; very few patients required re-escalation to Q4W. There were no new safety signals.
Constrictive pericarditis masquerading as hepatic sequestration crisis in a patient with sickle cell disease: a case report
Authors: Zathar Zafraan , James Sunil , Pressler Nickki , Ho Emily
Published: February 2020

Background

Constrictive pericarditis is a challenging diagnosis that is easily overlooked. Worldwide, tuberculosis (TB) is the leading cause; however, in the developed countries pericarditis and cardiac surgery are common aetiologies. Medical therapy can be sufficient in specific aetiologies preventing progression of constriction and thus surgery.

Case summary

A young student from Nigeria, with established sickle cell disease, presented with hepatomegaly and features of right heart failure. Following multiple investigations for hepatomegaly and pyrexia of unknown origin he was initially treated for hepatic sequestration crisis. After readmission with ongoing pyrexia, he was noted to have features of constrictive physiology on cardiac imaging. Constrictive pericarditis, secondary to TB, was suspected based on the patient’s background and clinical features. He was empirically commenced on anti-TB therapy after a positive interferon-gamma release assay test; Mycobacterium tuberculosis was later isolated in sputum cultures. He made a successful recovery with full radiological resolution of constrictive features on follow-up cardiac imaging.

Discussion

Constrictive pericarditis remains an elusive diagnosis in the context of coexisting medical problems. Revisiting the presentation and imaging helped in establishing the diagnosis. It is a potentially curable cause of diastolic heart failure with good outcomes if diagnosed and managed early. We were able to successfully manage the patient for TB constrictive pericarditis on medical therapy alone without surgical intervention.
G.N. Clark and the Oxford School of Modern History, 1919–1922: Hidden Origins of 1066 And All That
Authors: Rosebank Jon
Published: February 2020

W.C. Sellar and R.J. Yeatman’s 1066 and All That is a satirical history of England, published in 1930. It has long been thought to be a parody of popular history textbooks, characteristic of a generation of post-war writers disillusioned with the tone of patriotic English exceptionalism of many books. This paper explores contemporary critiques of history textbooks in the first third of the twentieth century and finds, however, that 1066 And All That is unusual in its implied criticism. It suggests that the standpoint of its authors reflects more than simply the recoil of their generation of ex-servicemen. It proposes that the book reflects their own particular experience of reading history at Oxford in 1919–22, at a time when teaching in the Modern History School still included much that was literary and whiggish. G.N. Clark had been their tutor, a historian close to C.H. Firth, Regius Professor of Modern History, and sympathetic to Firth’s long and controversial campaign for reform. While Clark’s later reputation was as a cautious scholar, as a young man he was a witty iconoclast, active in left-wing politics. We trace his influence on Sellar and Yeatman through the lectures they attended, and discover that 1066 And All That bears clear references to Clark’s reformist views on history at Oxford.
Treatment effect of bone-anchored maxillary protraction in growing patients compared to controls: a systematic review with meta-analysis
Authors: Cornelis Marie A , Tepedino Michele , Riis Neel de Vos , Niu Xiaowen , Cattaneo Paolo M
Published: February 2020

Objective

The aim of this systematic review was to determine which evidence level supports maxillary advancement after bone-anchored maxillary protraction (BAMP) in growing patients compared to controls.

Search methods

PubMed, Cochrane, Embase, Scopus, and Web-of-Science databases were searched with no restrictions on publication status or year.

Selection criteria

Prospective and retrospective human studies about BAMP, in at least three patients, were included. Authors were contacted when necessary, and reference lists of the included studies were screened.

Data collection and analysis

Two authors undertook independent data extraction with conflict resolution by a third author. Risks of bias were assessed. A meta-analysis for estimates of changes for ANB angle, Wits appraisal, and incisor to mandibular plane angle (IMPA) angle of BAMP treatment compared to control groups was performed.

Results

A total of 449 articles were initially retrieved; 28 full-text articles met the inclusion criteria. Sample sizes ranged from 3 to 52 patients. There was heterogeneity in cephalometric outcomes reported, which prevented the comparison of certain outcomes. ANB angle improved more with BAMP in the maxilla combined with facemask (bone-anchored facemask, BAFM) compared to traditional facemask therapy: this was statistically but not clinically significant (0.2 degrees). No data are available for BAMP with skeletal anchorage in both jaws in combination with Class III elastics (bone-anchored Class III elastics, BAC3E). Likewise, no statistically significant differences in Wits appraisal were found (less than 1 mm). Lower incisor retroclination and facial height seemed to be better controlled with BAC3E compared to BAFM.

Conclusions

The level of evidence available to support the maxillary advancement effect after BAMP was low. Publications reporting results based on identical samples tended to suggest overly positive results of BAMP. The differences in sagittal correction between BAMP and traditional facemask therapy were small and of questionable clinical significance. Long-term follow-up results are not available and, therefore, much needed.

Limitations

Most articles had a low level of evidence and some included a historical control group.

Registration

PROSPERO database number CRD42015023366.
The relationship between physical activity and out-of-pocket health care costs of the elderly in Europe
Authors: Dallmeyer Sören , Wicker Pamela , Breuer Christoph
Published: February 2020

Background

Increasing health care costs represent an economic burden placed on individuals across many European countries. Against this backdrop, the aim of this study was to examine the relationship between participation in physical activity and out-of-pocket health care costs in Europe.

Methods

Individual data from the cross-national Survey of Health, Ageing and Retirement (n = 94 267) including 16 European countries were utilized. Two-part models were estimated to investigate how different levels of participation frequency in physical activity are related to out-of-pocket costs (OOPC) for people aged 50 years and older.

Results

Only participation in physical activity more than once a week significantly decreases the probability of incurring any OOPC. However, all frequencies of physical activity significantly reduce the level of costs, with the highest savings being generated by participation once a week. The results reveal higher savings for men compared to women.

Conclusion

Physical activity can be a useful policy instrument to reduce the economic burden of out-of-pocket health care costs for an aging population in Europe. Public officials should primarily promote physical activity interventions targeting older people who are not active at all.
Initially Negative Affect Predicts Lower Satisfaction With Future Social Contact: A Time-Lagged Analysis Using Ecological Momentary Assessment
Authors: Liu Huiying , Fang Boye , Li Yuekang , Lou Vivian W Q
Published: February 2020

Objectives

Prior research has linked subjective features of social situations with short-term changes in affect (e.g., across days, hours), but little is known about the directionality of such links. Our study examined the concurrent and lead–lag relationships between social contact satisfaction and affect in the flow of daily life.

Method

Using ecological momentary assessment (EMA), wherein 78 late-middle-aged and older adults reported on 2,739 social contacts (average 5.02 per day, SD = 2.95) across seven consecutive days, we examined how the level of social contact satisfaction was concurrently and prospectively associated with affect (high-arousal and low-arousal positive affect [PA], high-arousal and low-arousal negative affect [NA]).

Results

Higher contact satisfaction was concurrently associated with more high- and low-arousal PA and less high- and low-arousal NA. The influence of contact satisfaction remains for predicting greater low-arousal PA (quietness, calmness) during the next social contact. NA (either high- or low-arousal) predicted lower satisfaction during the next social contact, but such sustainable influence was not observed for PA.

Discussion

The study reveals a cycle in which elevated NA may trigger unsatisfactory social contact, which subsequently predicted less low-arousal PA such as quietness and calmness. Our study provided a more nuanced and differentiated picture of the temporal sequencing of everyday social contact and momentary affect. Practitioners may gain insights from our study into the development of just-in-time adaptive interventions that aim for the betterment of affective well-being in old age.
Accelerated full-waveform inversion using dynamic mini-batches
Authors: van Herwaarden Dirk Philip , Boehm Christian , Afanasiev Michael , Thrastarson Solvi , Krischer Lion , Trampert Jeannot , Fichtner Andreas
Published: February 2020

We present an accelerated full-waveform inversion based on dynamic mini-batch optimization, which naturally exploits redundancies in observed data from different sources. The method rests on the selection of quasi-random subsets (mini-batches) of sources, used to approximate the misfit and the gradient of the complete data set. The size of the mini-batch is dynamically controlled by the desired quality of the gradient approximation. Within each mini-batch, redundancy is minimized by selecting sources with the largest angular differences between their respective gradients, and spatial coverage is maximized by selecting candidate events with Mitchell’s best-candidate algorithm. Information from sources not included in a specific mini-batch is incorporated into each gradient calculation through a quasi-Newton approximation of the Hessian, and a consistent misfit measure is achieved through the inclusion of a control group of sources. By design, the dynamic mini-batch approach has several main advantages: (1) The use of mini-batches with adaptive size ensures that an optimally small number of sources is used in each iteration, thus potentially leading to significant computational savings; (2) curvature information is accumulated and exploited during the inversion, using a randomized quasi-Newton method; (3) new data can be incorporated without the need to re-invert the complete data set, thereby enabling an evolutionary mode of full-waveform inversion. We illustrate our method using synthetic and real-data inversions for upper-mantle structure beneath the African Plate. In these specific examples, the dynamic mini-batch approach requires around 20 per cent of the computational resources in order to achieve data and model misfits that are comparable to those achieved by a standard full-waveform inversion where all sources are used in each iteration.
Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB
Authors: Bicak Mesude , Wang Xing , Gao Xiaoni , Xu Xing , Väänänen Riina-Minna , Taimen Pekka , Lilja Hans , Pettersson Kim , Klein Robert J
Published: February 2020

How genome-wide association studies-identified single-nucleotide polymorphisms (SNPs) affect remote genes remains unknown. Expression quantitative trait locus (eQTL) association meta-analysis on 496 prostate tumor and 602 normal prostate samples with 117 SNPs revealed novel cis-eQTLs and trans-eQTLs. Mediation testing and colocalization analysis demonstrate that MSMB is a cis-acting mediator for SNHG11 (P < 0.01). Removing rs10993994 in LNCaP cell lines by CRISPR/Cas9 editing shows that the C-allele corresponds with an over 100-fold increase in MSMB expression and 5-fold increase in SNHG11 compared with the T-allele. Colocalization analysis confirmed that the same set of SNPs associated with MSMB expression is associated with SNHG11 expression (posterior probability of shared variants is 66.6% in tumor and 91.4% in benign). These analyses further demonstrate variants driving MSMB expression differ in tumor and normal, suggesting regulatory network rewiring during tumorigenesis.
The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?
Authors: Peeri Noah C , Shrestha Nistha , Rahman Md Siddikur , Zaki Rafdzah , Tan Zhengqi , Bibi Saana , Baghbanzadeh Mahdi , Aghamohammadi Nasrin , Zhang Wenyi , Haque Ubydul
Published: February 2020

Objectives

To provide an overview of the three major deadly coronaviruses and identify areas for improvement of future preparedness plans, as well as provide a critical assessment of the risk factors and actionable items for stopping their spread, utilizing lessons learned from the first two deadly coronavirus outbreaks, as well as initial reports from the current novel coronavirus (COVID-19) epidemic in Wuhan, China.

Methods

Utilizing the Centers for Disease Control and Prevention (CDC, USA) website, and a comprehensive review of PubMed literature, we obtained information regarding clinical signs and symptoms, treatment and diagnosis, transmission methods, protection methods and risk factors for Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS) and COVID-19. Comparisons between the viruses were made.

Results

Inadequate risk assessment regarding the urgency of the situation, and limited reporting on the virus within China has, in part, led to the rapid spread of COVID-19 throughout mainland China and into proximal and distant countries. Compared with SARS and MERS, COVID-19 has spread more rapidly, due in part to increased globalization and the focus of the epidemic. Wuhan, China is a large hub connecting the North, South, East and West of China via railways and a major international airport. The availability of connecting flights, the timing of the outbreak during the Chinese (Lunar) New Year, and the massive rail transit hub located in Wuhan has enabled the virus to perforate throughout China, and eventually, globally.

Conclusions

We conclude that we did not learn from the two prior epidemics of coronavirus and were ill-prepared to deal with the challenges the COVID-19 epidemic has posed. Future research should attempt to address the uses and implications of internet of things (IoT) technologies for mapping the spread of infection.
H∞ output tracking bumpless transfer control for switched linear systems
Authors: Zhao Ying , Zhao Jun
Published: February 2020

This study concentrates on the problem of $H_\infty $ output tracking bumpless transfer control for a category of switched linear systems (SLSs). The $H_\infty $ output tracking bumpless transfer control problem is to ensure the SLSs to satisfy the bumpless transfer performance and the $H_\infty $ output tracking properties by co-design of a switching rule and a series of controllers. Firstly, a concept of the bumpless transfer performance for a system in this class is presented. Then, via a Lyapunov function scheme, criteria guaranteeing the bumpless transfer performance and the $H_\infty $ output tracking properties are established. The criteria allow the problem of the $H_\infty $ output tracking bumpless transfer control for subsystems is unsolvable. Finally, an example of controlling a turbofan model is offered for the verification on the effectiveness of the presented control strategy.
Do genetic variations in proximal tubule transporters influence tenofovir-induced renal dysfunction? An exploratory study in a Ghanaian population
Authors: Neary M , Olagunju A , Sarfo F , Phillips R , Moss D , Owen A , Chadwick D
Published: February 2020

Objectives

To assess associations between polymorphisms within genes encoding proximal tubule transporters implicated in tenofovir renal clearance and kidney tubular dysfunction (KTD), chronic kidney disease (CKD) and individual biochemical parameters.

Patients and methods

The study included a cohort of HIV-positive Ghanaians receiving regimens containing tenofovir disoproxil fumarate (n = 66) for at least 6 months prior to study enrolment. SNPs in ABCC10, ABCC2 and ABCC4 were selected for analysis based on previous published associations. All SNPs were genotyped by real-time PCR allelic discrimination. Creatinine clearance (CLCR), serum and urine creatinine concentrations and biochemical measures of KTD were assessed. Statistical significance was determined through univariate linear or binary logistical regression (P ≤ 0.05).

Results

None of the SNPs evaluated was associated with CKD or KTD. A trend between body weight and higher incidence of CKD (P = 0.012, OR = 0.9) was observed. ABCC10 2843T>C (rs2125739) was significantly associated with lower log10 baseline creatinine (P = 0.001, β= −0.4), higher baseline CLCR (P = 0.008, β = 65.2) and lower CLCR after 1 year (P = 0.024, β= −26.6).

Conclusions

This study demonstrates an association of ABCC10 rs2125739 with indicators of declining renal function and builds on current knowledge of this interaction within a Ghanaian cohort.
A Rapid Multiresidue Method for Determination of Pesticides in Fruits and Vegetables by Using Acetonitrile Extraction/Partitioning and Solid-Phase Extraction Column Cleanup
Authors: Schenck Frank J , Brown Amy N , Podhorniak Lynda V , Parker Alesia , Reliford Michelle , Wong Jon W
Published: February 2020

A modification of a rapid and inexpensive multiresidue method for determination of pesticides in fruits and vegetables (QuEChERS method) is presented. Samples were extracted by shaking with acetic acidacetonitrile (1 + 99). Water was removed by liquidliquid partitioning with magnesium sulfate and sodium acetate. The extract was subjected to a single solid-phase extraction (SPE) column cleanup, which produced a cleaner extract than did the dispersive SPE cleanup used in the original QuEChERS method. Recovery data were obtained for 316 pesticide residues, at levels ranging from 20 ppb to 1.0 ppm. Data were provided by 3 different laboratories. The modified QuEChERS method resulted in a 65 reduction in solvent usage, when compared with the traditional multiresidue methods previously used in our laboratories.