bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational high throughput screening of inorganic cation based halide perovskites for perovskite only tandem solar cells
Authors: Kar M , Körzdörfer T
Published: April 2020

We search for homovalent alternatives for A, B, and X-ions in ABX3 type inorganic halide perovskites suitable for tandem solar cell applications. We replace the conventional A-site organic cation CH3NH3, by 3 inorganic cations, Cs, K, and Rb, and the B site consists of metals; Cd, Hg, Ge, Pb, and Sn This work is built on our previous high throughput screening of hybrid perovskite materials (Kar et al 2018 J. Chem. Phys.
149, 214701). By performing a systematic screening study using Density Functional Theory (DFT) methods, we found 11 suitable candidates; 2 Cs-based, 3 K-based and 6 Rb-based that are suitable for tandem solar cell applications.
An updated LLVM-based quantum research compiler with further OpenQASM support
Authors: Litteken Andrew , Fan Yung-Ching , Singh Devina , Martonosi Margaret , Chong Frederic T
Published: April 2020

Quantum computing is a rapidly growing field with the potential to change how we solve previously intractable problems. Emerging hardware is approaching a complexity that requires increasingly sophisticated programming and control. Scaffold is an older quantum programming language that was originally designed for resource estimation for far-future, large quantum machines, and ScaffCC is the corresponding LLVM-based compiler. For the first time, we provide a full and complete overview of the language itself, the compiler as well as its pass structure. While previous works Abhari et al (2015 Parallel Comput.
45 2–17), Abhari et al (2012 Scaffold: quantum programming language https://cs.princeton.edu/research/techreps/TR-934-12), have piecemeal descriptions of different portions of this toolchain, we provide a more full and complete description in this paper. We also introduce updates to ScaffCC including conditional measurement and multidimensional qubit arrays designed to keep in step with modern quantum assembly languages, as well as an alternate toolchain targeted at maintaining correctness and low resource count for noisy-intermediate scale quantum (NISQ) machines, and compatibility with current versions of LLVM and Clang. Our goal is to provide the research community with a functional LLVM framework for quantum program analysis, optimization, and generation of executable code.
Review on exsolution and its driving forces in perovskites
Authors: Kwon Ohhun , Joo Sangwook , Choi Sihyuk , Sengodan Sivaprakash , Kim Guntae
Published: April 2020

Exsolution is a promising method to design metal nanoparticles for electrocatalysis and renewable energy. Metal nanoparticles exsolved from perovskite oxide lattices have been utilized as catalysts in many energy fields because of their high durability and excellent electro-catalytic properties. Although this method has received much attention in recent years, a comprehensive understanding is still lacking because of difficulties in finding a rational combination of driving forces and perovskite supports. Thus, the aim of our work here is to recapitulate the principles of exsolution and collect various exsolution studies by categorizing the driving forces of exsolution and the structural characteristics of perovskite supports. These classifications provide guidelines for selecting suitable materials groups and remodeling existing materials, thereby exploring applications of catalysts using exsolution that are applicable to academic and industrial fields.
Phytogreen synthesis of multifunctional nano selenium with antibacterial and antioxidant implications
Authors: Matai Ishita , Pandey Satish Kumar , Garg Deepa , Rani Komal , Sachdev Abhay
Published: April 2020

The exploitation of plant extracts for the synthesis of nano selenium having antibacterial and antioxidant activities is an exciting approach to counteract the prevalence of infections caused by antibiotic-resistant bacteria, which holds relevance for medical and food industries. In the present work, a green and facile method for the preparation of nano selenium (nSe) using the fruit extract of Indian gooseberry (Phyllanthus Emblica) has been reported. The optical and structural properties of the as-synthesized nSe were studied through various characterization techniques. Eventually, the antioxidant potential of nSe was investigated via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl free radical scavenging assays. Parallely, the antibacterial activity of nSe against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa was evaluated. The antioxidant assays indicated that even low dosage of nSe showed excellent activity with EC50 values of 0.21 μg ml−1 and 3.34 μg ml−1, respectively. Moreover, nSe exhibited significant inhibition in bacterial growth at low minimum inhibitory concentration (MIC) values against Escherichia coli (16 μg ml−1), Staphylococcus aureus (32 μg ml−1) and Pseudomonas aeruginosa (48 μg ml−1) compared to MIC values for standard drug ampicillin. Importantly, nSe did not induce any cytotoxic effects on normal human keratinocytes (HaCaT) at the tested concentrations; representing their biocompatible nature. The data obtained demonstrated the versatility of phytogreen nSe as a potent antioxidant and antibacterial agent to effectively prevent as well as treat multidrug-resistant bacterial infections.
Seiberg-Witten equation on a manifold with rank-2 foliation
Authors: Lin Dexie
Published: April 2020

Let

M
M

be a closed oriented

4
4

-manifold admitting a rank-

2
2

oriented foliation with a metric of leafwise positive scalar curvature. If

b
+

>
1

b^+>1

, then we will show that the Seiberg-Witten invariant vanishes for all

s
p
i
n

c

\mathrm {spin}^c

structures.
Polynomial hulls of arcs and curves
Authors: Izzo Alexander
Published: April 2020

It is shown that there exist arcs and simple closed curves in

C

3

\mathbb {C}^3

with nontrivial polynomial hulls that contain no analytic discs. It is also shown that in any bounded, connected Runge domain of holomorphy in

C

N

\mathbb {C}^N

(

N
≥
2

N \geq 2

) there exist polynomially convex arcs and simple closed curves of almost full measure. These results, which strengthen earlier results of the author, are obtained as consequences of a general result about polynomial hulls of arcs and simple closed curves through compact, totally disconnected sets.
Möbius disjointness for nilsequences along short intervals
Authors: He Xiaoguang , Wang Zhiren
Published: April 2020

For a nilmanifold

G

/

Γ

G/\Gamma

, a

1
1

-Lipschitz continuous function

F
F

and the Möbius sequence

μ
(
n
)

\mu (n)

, we prove a bound on the decay of the averaged short interval correlation
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartFraction 1 Over upper H upper N EndFraction sigma-summation Underscript n less-than-or-equal-to upper N Endscripts StartAbsoluteValue sigma-summation Underscript h less-than-or-equal-to upper H Endscripts mu left-parenthesis n plus h right-parenthesis upper F left-parenthesis g Superscript n plus h Baseline x right-parenthesis EndAbsoluteValue">

1

H
N

∑

n
≤
N

|

∑

h
≤
H

μ
(
n
+
h
)
F
(

g

n
+
h

x
)

|

\begin{equation*} \frac {1}{HN}\sum _{n\leq N}\Big |\sum _{h\leq H} \mu (n+h)F(g^{n+h}x)\Big | \end{equation*}

as

H
,
N
→
∞

H,N\to \infty

. The bound is uniform in

g
∈
G

g\in G

,

x
∈
G

/

Γ

x\in G/\Gamma

and

F
F

.
Contributions of Liquid-Based (Papanicolaou) Cytology and Human Papillomavirus Testing in Cotesting for Detection of Cervical Cancer and Precancer in the United States
Authors: Kaufman Harvey W , Alagia Damian P , Chen Zhen , Onisko Agnieszka , Austin R Marshall
Published: April 2020

Objectives

Given the recent debate challenging the contribution of cytology in cervical screening, we evaluated results of liquid-based cytology (LBC) and human papillomavirus (HPV) testing in cotesting preceding cervical cancer (CxCa) and precancer diagnoses in a national, heterogeneous population.

Methods

We assessed the results of cotesting, performed by Quest Diagnostics, in 13,633,071 women 30 years and older, tested 2010 to 2018. Cotest results preceding CxCa or precancer diagnoses were analyzed and stratified by histopathology.

Results

Among all screening results, 1,615 cotests preceded 1,259 CxCa diagnoses, and 11,164 cotests preceded 8,048 cervical precancer diagnoses. More women who were subsequently diagnosed with CxCa within 1 year were identified by the LBC result than by the HPV result (85.1%, 1,015/1,193 vs 77.5%, 925/1,193). Among all women with CxCa, the overall rate of nondetection was 13.1% (212/1,615) for cotesting results (LBC negative/HPV negative) and this rate increased substantially when testing exceeded 12 months compared to within 1 year prediagnosis of either CxCa or precancer.

Conclusions

Analysis of 9-year cotest results from a national reference laboratory confirms the value of LBC element in cotesting. This supports that LBC/HPV cotesting enhances screening for the identification of CxCa in women 30 years and older, more so than LBC or HPV alone within cotesting.
Histologic Findings of Uterine Niches
Authors: Karpathiou Georgia , Chauleur Celine , Dridi Maroa , Baillard Pauline , Corsini Thomas , Dumollard Jean Marc , Peoc’h Michel
Published: April 2020

Objectives

The disruption or defect of the myometrium in the uterine scar of a cesarean section (CS) has been known by various names, such as uterine niche, isthmocele, deficient uterine scar, scar pouch, or diverticulum. Symptomatology, risk factors for niche development, and available treatment modalities have been recently studied. However, the histologic features of this disease remain unknown.

Methods

The histologic features of eight uterine niches are thoroughly described and a summary of the most important aspects of the uterine niche literature is provided. Five cases of CS scars without niche formation are comparatively examined.

Results

Most uterine niches harbor endocervical mucosa, often cystically dilated and/or an atrophic or disorganized endometrial mucosa of lower uterine segment origin. Regenerative epithelial atypia and fibroblastic stromal reaction are frequent features. No granulomatous reaction, important inflammation, or hemorrhage is seen. CS scars without niche formation do not harbor endocervical mucosa or inclusion cysts, fibroblastic stroma, or regenerative atypia.

Conclusions

As more prospective studies of uterine niche development and treatment will be conducted, a detailed pathologic report with the criteria proposed herein can be designed.
Nodding syndrome: a concise review
Authors: Olum Sam , Scolding Peter , Hardy Charlotte , Obol James , Scolding Neil J
Published: April 2020

Nodding syndrome is an uncommon epileptic disorder of childhood onset, which appears to occur exclusively in clusters in sub-Saharan Africa. It was first reported in the 1960s, in what is now southern Tanzania, then in Liberia, and later in South Sudan and northern Uganda, with both epidemic and endemic patterns described. The cause remains unknown. Here we describe the background and development of descriptions of the disorder, review its clinical features and summarize current theories and studies concerning its cause, outlining the principal remaining research questions relating to this highly unusual disease.
Quantifying epileptogenesis in rats with spontaneous and responsive brain state dynamics
Authors: Crisp Dakota N , Cheung Warwick , Gliske Stephen V , Lai Alan , Freestone Dean R , Grayden David B , Cook Mark J , Stacey William C
Published: April 2020

There is a crucial need to identify biomarkers of epileptogenesis that will help predict later development of seizures. This work identifies two novel electrophysiological biomarkers that quantify epilepsy progression in a rat model of epileptogenesis. The long-term tetanus toxin rat model was used to show the development and remission of epilepsy over several weeks. We measured the response to periodic electrical stimulation and features of spontaneous seizure dynamics over several weeks. Both biomarkers showed dramatic changes during epileptogenesis. Electrically induced responses began to change several days before seizures began and continued to change until seizures resolved. These changes were consistent across animals and allowed development of an algorithm that could differentiate which animals would later develop epilepsy. Once seizures began, there was a progression of seizure dynamics that closely follows recent theoretical predictions, suggesting that the underlying brain state was changing over time. This research demonstrates that induced electrical responses and seizure onset dynamics are useful biomarkers to quantify dynamical changes in epileptogenesis. These tools hold promise for robust quantification of the underlying epileptogenicity and prediction of later development of seizures.
PC4 serves as a negative regulator of skin wound healing in mice
Authors: Liao Fengying , Chen Long , Luo Peng , Jiang Zhongyong , Chen Zelin , Wang Ziwen , Zhang Chi , Wang Yu , He Jintao , Wang Qing , Wang Yawei , Liu Lang , Huang Yu , Wang Huilan , Jiang Qingzhi , Luo Min , Gan Yibo , Liu Yunsheng , Wang Yang , Wu Jie , Xie Wentao , Cheng Zhuo , Dai Yali , Li Jialun , Liu Zujuan , Yang Fan , Shi Chunmeng
Published: April 2020

Background

Human positive cofactor 4 (PC4) was initially characterized as a multifunctional transcriptional cofactor, but its role in skin wound healing is still unclear. The purpose of this study was to explore the role of PC4 in skin wound healing through PC4 knock-in mouse model.

Methods

A PC4 knock-in mouse model (PC4+/+) with a dorsal full-thickness wound was used to investigate the biological functions of PC4 in skin wound healing. Quantitative PCR, Western blot analysis and immunohistochemistry were performed to evaluate the expression of PC4; Sirius red staining and immunofluorescence were performed to explore the change of collagen deposition and angiogenesis. Proliferation and apoptosis were detected using Ki67 staining and TUNEL assay. Primary dermal fibroblasts were isolated from mouse skin to perform cell scratch experiments, cck-8 assay and colony formation assay.

Results

The PC4+/+ mice were fertile and did not display overt abnormalities but showed an obvious delay in cutaneous healing of dorsal skin. Histological staining showed insufficient re-epithelialization, decreased angiogenesis and collagen deposition, increased apoptosis and decreased cell proliferation in PC4+/+ skin. Our data also showed decreased migration rate and proliferation ability in cultured primary fibroblasts from PC4+/+ mice in vitro.

Conclusions

This study suggests that PC4 might serve as a negative regulator of skin wound healing in mice.
Renewal and Differentiation of GCD Necklace Olfactory Sensory Neurons
Authors: Bloom Maria Lissitsyna , Johnston Lucille B , Datta Sandeep Robert
Published: April 2020

Both canonical olfactory sensory neurons (OSNs) and sensory neurons belonging to the guanylate cyclase D (GCD) “necklace” subsystem are housed in the main olfactory epithelium, which is continuously bombarded by toxins, pathogens, and debris from the outside world. Canonical OSNs address this challenge, in part, by undergoing renewal through neurogenesis; however, it is not clear whether GCD OSNs also continuously regenerate and, if so, whether newborn GCD precursors follow a similar developmental trajectory to that taken by canonical OSNs. Here, we demonstrate that GCD OSNs are born throughout adulthood and can persist in the epithelium for several months. Phosphodiesterase 2A is upregulated early in the differentiation process, followed by the sequential downregulation of β-tubulin and the upregulation of CART protein. The GCD and MS4A receptors that confer sensory responses upon GCD neurons are initially expressed midway through this process but become most highly expressed once CART levels are maximal late in GCD OSN development. GCD OSN maturation is accompanied by a horizontal migration of neurons toward the central, curved portions of the cul-de-sac regions where necklace cells are concentrated. These findings demonstrate that—like their canonical counterparts—GCD OSNs undergo continuous renewal and define a GCD-specific developmental trajectory linking neurogenesis, maturation, and migration.
Discriminative Ability and Reliability of Transesophageal Echocardiography in Characterizing Cases of Cardiac Device Lead Vegetations Versus Noninfectious Echodensities
Authors: George Merit P , Esquer Garrigos Zerelda , Vijayvargiya Prakhar , Anavekar Nandan S , Luis Sushil Allen , Wilson Walter R , Baddour Larry M , Sohail M Rizwan
Published: April 2020

Background

Approximately one-third of cases of cardiovascular implantable electronic device (CIED) infection present as CIED lead infection. The precise transesophageal echocardiographic (TEE) definition and characterization of “vegetation” associated with CIED lead infection remain unclear.

Methods

We identified a sample of 25 consecutive cases of CIED lead infection managed at our institution between January 2010 and December 2017. Cases of CIED lead infection were classified using standardized definitions. Similarly, a sample of 25 noninfected patients who underwent TEE that showed a defined lead echodensity during the study period was included as a control group. TEEs were reviewed by 2 independent echocardiologists who were blinded to all linked patient demographic, clinical, and microbiological information. Reported echocardiographic variables of the infected vs noninfected cases were compared, and the overall diagnostic performance was analyzed.

Results

Descriptions of lead echodensities were variable and there were no significant differences in median echodensity diameter or mobility between infected vs noninfected groups. Among infected cases, blinded echocardiogram reports by either reviewer correctly made a prediction of infection in 6 of 25 (24%). Interechocardiologist agreement was 68%. Sensitivity of blinded TEEs ranged from 31.5% to 37.5%.

Conclusions

Infectious vs noninfectious lead echodensities could not be reliably distinguished on the basis of size, mobility, and general shape descriptors obtained from a retrospective blinded TEE examination without knowledge of clinical and microbiological parameters. Therefore, a reanalysis of criteria used to support a diagnosis of CIED lead infection may be warranted.
Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients With COVID-19 (April 2020)
Authors: Bhimraj Adarsh , Morgan Rebecca L , Shumaker Amy Hirsch , Lavergne Valery , Baden Lindsey , Cheng Vincent Chi-Chung , Edwards Kathryn M , Gandhi Rajesh , Muller William J , O’Horo John C , Shoham Shmuel , Murad M Hassan , Mustafa Reem A , Sultan Shahnaz , Falck-Ytter Yngve
Published: April 2020

Background

There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19). There is a need for frequently updated practice guidelines on their use, based on critical evaluation of rapidly emerging literature. The objective was to develop evidence-based rapid guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19.

Methods

The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise. Process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations.

Results

The IDSA guideline panel agreed on 7 treatment recommendations and provided narrative summaries of other treatments undergoing evaluations.

Conclusions

The panel expressed the overarching goal that patients be recruited into ongoing trials, which would provide much-needed evidence on the efficacy and safety of various therapies for COVID-19, given that we could not make a determination whether the benefits outweigh harms for most treatments.
Development and Validation of the IBD-REFER Criteria: Early Referral for Suspected Inflammatory Bowel Diseases in Adults and Children
Authors: Atia Ohad , Shosberger Adi , Focht Gili , Ledder Oren , Lev-Tzion Raffi , Navon Dan , Assa Amit , Yerushalmi Baruch , Shaoul Ron , Shouval Dror S , Bar-Gil Shitrit Ariella , Koslowsky Benjamin , Dotan Iris , Kariv Revital , Lavon Eitan , Turner Dan
Published: April 2020

Background

Early treatment of inflammatory bowel disease (IBD) is associated with positive outcomes but a significant diagnostic delay has been reported in most countries.

Aim

We aimed to develop and validate IBD-REFER criteria, intended for primary care physicians, to screen patients at risk for IBD.

Methods

A Delphi group of 10 experts generated a list of symptoms associated with the onset of IBD, supplemented by a review of the literature. The list was reduced in an iterative process and graded based on importance. For data-driven statistical formatting, the charts of 200 IBD (100 children, 100 adults) and 100 non-IBD controls but with gastrointestinal symptoms were reviewed. The IBD-REFER items were scored for each subject, as well as the contending Red Flag criteria from the International Organization for the Study of IBD. External validation was performed on additionally enrolled cohorts of 100 IBD patients and 50 controls.

Results

The Delphi process retained 5 items as major criteria (≥1 item required for early referral) and 11 as minor (≥2 items required). Following the removal of uninformative items and further formatting in the data-driven stage, 10 core items were retained: 3 as major and 7 as minor. In the external validation, the final IBD-REFER criteria had a sensitivity/specificity of 98%/96% in adults and 96%/96% in children, significantly higher than achieved by the Red Flag criteria (71%/84% and 60%/88%, respectively; P < 0.001).

Conclusion

The IBD-REFER criteria may guide the selection of patients for expedited gastrointestinal investigation.
Economic Outcomes of Inflammatory Bowel Disease Patients Switching to a Second Anti-Tumor Necrosis Factor or Vedolizumab
Authors: Chiorean Michael , Afzali Anita , Cross Raymond K , Macaulay Dendy , Griffith Jenny , Wang Anthony , Garcia-Horton Viviana
Published: April 2020

Background

Anti-tumor necrosis factor (TNF) therapies have been the mainstay of inflammatory bowel disease (IBD) treatment for nearly 2 decades. Therapies with novel mechanisms of action have been recently developed. This study compared healthcare resource utilization (HRU) and costs incurred while switching from an initial anti-TNF to another anti-TNF versus switching to vedolizumab.

Methods

Adults with IBD who switched from initial anti-TNF to another anti-TNF or vedolizumab were identified from Truven MarketScan claims database (January 1, 2000–September 30, 2017). Patient characteristics were assessed during the 6-month period before the initiation date of the switched-to treatment (index date). Adjusted analyses of all-cause and disease-related HRU and costs during the 6-month period after the index date (study period) were performed. Anti-TNF and vedolizumab switchers with Crohn’s disease (CD) and ulcerative colitis (UC) were separately compared.

Results

A total of 502 vedolizumab, 1708 adalimumab, 755 infliximab, and 703 other switchers with CD and 461, 428, 311, and 148 with UC, respectively, were identified. Patient demographics were similar across cohorts. Total all-cause costs were significantly higher for vedolizumab than adalimumab, infliximab, and certolizumab switchers in the CD cohort and adalimumab and infliximab in the UC cohort. In both cohorts, adalimumab and other switchers had fewer all-cause and IBD-related outpatient visits than vedolizumab switchers.

Conclusions

CD/UC patients who switched to vedolizumab from initial anti-TNF had higher total and treatment costs than patients who switched to another anti-TNF, except for UC patients who switched to golimumab. Prospective studies should be conducted to confirm these findings.
Human influenza A virus causes myocardial and cardiac-specific conduction system infections associated with early inflammation and premature death
Authors: Filgueiras-Rama David , Vasilijevic Jasmina , Jalife Jose , Noujaim Sami F , Alfonso Jose M , Nicolas-Avila Jose A , Gutierrez Celia , Zamarreño Noelia , Hidalgo Andres , Bernabé Alejandro , Cop Christopher Pablo , Ponce-Balbuena Daniela , Guerrero-Serna Guadalupe , Calle Daniel , Desco Manuel , Ruiz-Cabello Jesus , Nieto Amelia , Falcon Ana
Published: April 2020

Aims

Human influenza A virus (hIAV) infection is associated with important cardiovascular complications, although cardiac infection pathophysiology is poorly understood. We aimed to study the ability of hIAV of different pathogenicity to infect the mouse heart, and establish the relationship between the infective capacity and the associated in vivo, cellular and molecular alterations.

Methods and results

We evaluated lung and heart viral titres in mice infected with either one of several hIAV strains inoculated intranasally. 3D reconstructions of infected cardiac tissue were used to identify viral proteins inside mouse cardiomyocytes, Purkinje cells, and cardiac vessels. Viral replication was measured in mouse cultured cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to confirm infection and study underlying molecular alterations associated with the in vivo electrophysiological phenotype. Pathogenic and attenuated hIAV strains infected and replicated in cardiomyocytes, Purkinje cells, and hiPSC-CMs. The infection was also present in cardiac endothelial cells. Remarkably, lung viral titres did not statistically correlate with viral titres in the mouse heart. The highly pathogenic human recombinant virus PAmut showed faster replication, higher level of inflammatory cytokines in cardiac tissue and higher viral titres in cardiac HL-1 mouse cells and hiPSC-CMs compared with PB2mut-attenuated virus. Correspondingly, cardiac conduction alterations were especially pronounced in PAmut-infected mice, associated with high mortality rates, compared with PB2mut-infected animals. Consistently, connexin43 and NaV1.5 expression decreased acutely in hiPSC-CMs infected with PAmut virus. YEM1L protease also decreased more rapidly and to lower levels in PAmut-infected hiPSC-CMs compared with PB2mut-infected cells, consistent with mitochondrial dysfunction. Human IAV infection did not increase myocardial fibrosis at 4-day post-infection, although PAmut-infected mice showed an early increase in mRNAs expression of lysyl oxidase.

Conclusion

Human IAV can infect the heart and cardiac-specific conduction system, which may contribute to cardiac complications and premature death.
Intestinal CD14+ Macrophages Protect CD4+ T Cells From Activation-induced Cell Death via Exosomal Membrane TNF in Crohn’s Disease
Authors: Liu Huashan , Liang Zhenxing , Wang Fengwei , Zheng Xiaobin , Zeng Ziwei , He Xiaowen , Gao Xiang , Zhi Min , Wu Xiaojian , Wu Xianrui , Lan Ping
Published: April 2020

Background and aims

Sustained activation of CD4+ T cells plays important roles in the pathogenesis of Crohn’s disease [CD]. Under physiologic conditions, activated T cells can be timely eliminated by a process termed activation-induced cell death [AICD], restraining T cell over-activation and preventing immunological destruction. We inquired whether defective AICD might explain CD4+ T cell over-activation in CD and investigated the underlying mechanisms.

Methods

CD14+ macrophages [Mφ] and CD4+ T cells were isolated from intestinal tissues or peripheral blood of controls and CD patients. An ex vivo evaluation system was employed to simulate AICD and cell apoptosis was measured by flow cytometry.

Results

CD4+ T cells from CD patients fail to undergo AICD in the ex vivo system. Specifically, proinflammatory type 1 helper T [Th1] and type 17 helper T [Th17] cells, rather than immunosuppressive regulatory T [Treg] cells evade AICD in CD. CD14+ Mφ in the intestinal inflammatory microenvironment of CD promote AICD resistance in CD4+ T cells via a cell-to-cell contact-independent manner. Mechanistically, CD14+ Mφ released exosomes express membrane tumour necrosis factor [TNF] which engages TNFR2 on CD4+ T cells and triggers NF-κB signalling, thereby causing AICD resistance. Importantly, clinically applicable anti-TNF antibodies effectively blocked exosomal membrane TNF-induced CD4+ T cell AICD resistance.

Conclusions

CD14+ Mφ participate in CD pathogenesis by inducing AICD resistance through release of exosomal membrane TNF to activate the TNFR2/NF-κB pathway in CD4+ T cells. These results present new insights into CD pathogenesis and extend mechanistic understanding of anti-TNF agents.

Proposed model

CD14+ Mφ in the intestinal microenvironment of CD patients maintain the sustained activation of CD4+ T cells through exosomal membrane TNF to induce apoptosis resistance via TNFR2/NF-κB signalling, which could be effectively blocked by clinically applicable anti-TNF agents.
Identification of anticancer drugs associated with atrial fibrillation: analysis of the WHO pharmacovigilance database
Authors: Alexandre Joachim , Salem Joe-Elie , Moslehi Javid , Sassier Marion , Ropert Camille , Cautela Jennifer , Thuny Franck , Ederhy Stéphane , Cohen Ariel , Damaj Ghandi , Vilque Jean-Pierre , Plane Anne-Flore , Legallois Damien , Champ-Rigot Laure , Milliez Paul , Funck-Brentano Christian , Dolladille Charles
Published: April 2020

Aims

The explosion of novel anticancer therapies has meant emergence of cardiotoxicity signals including atrial fibrillation (AF). Reliable data concerning the liability of anticancer drugs in inducing AF are scarce. Using the World Health Organization individual case safety report database, VigiBase®, we aimed to determine the association between anticancer drugs and AF.

Methods and results

A disproportionality analysis evaluating the multivariable-adjusted reporting odds ratios for AF with their 99.97% confidence intervals was performed for 176 U.S. Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-labelled anticancer drugs in VigiBase®, followed by a descriptive analysis of AF cases for the anticancer drugs identified in VigiBase®. ClinicalTrial registration number: NCT03530215. A total of 11 757 AF cases associated with at least one anticancer drug were identified in VigiBase® of which 95.8% were deemed serious. Nineteen anticancer drugs were significantly associated with AF of which 14 (74%) are used in haematologic malignancies and 9 (45%) represented new AF associations not previously confirmed in literature including immunomodulating agents (lenalidomide, pomalidomide), several kinase inhibitors (nilotinib, ponatinib, midostaurin), antimetabolites (azacytidine, clofarabine), docetaxel (taxane), and obinutuzumab, an anti-CD20 monoclonal antibody.

Conclusion

Although cancer malignancy itself may generate AF, we identified 19 anticancer drugs significantly associated with a significant increase in AF over-reporting. This pharmacovigilance study provides evidence that anticancer drugs themselves could represent independent risk factors for AF development. Dedicated prospective clinical trials are now required to confirm these 19 associations. This list of suspected anticancer drugs should be known by physicians when confronted to AF in cancer patients, particularly in case of haematologic malignancies.
Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction
Authors: Hung John , Roos Andreas , Kadesjö Erik , McAllister David A , Kimenai Dorien M , Shah Anoop S V , Anand Atul , Strachan Fiona E , Fox Keith A A , Mills Nicholas L , Chapman Andrew R , Holzmann Martin J
Published: April 2020

Aims

The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with myocardial infarction. However, its performance in type 2 myocardial infarction is uncertain.

Methods and results

In two cohorts of consecutive patients with suspected acute coronary syndrome from 10 hospitals in Scotland (n = 48 282) and a tertiary care hospital in Sweden (n = 22 589), we calculated the GRACE 2.0 score to estimate death at 1 year. Discrimination was evaluated by the area under the receiver operating curve (AUC), and compared for those with an adjudicated diagnosis of type 1 and type 2 myocardial infarction using DeLong’s test. Type 1 myocardial infarction was diagnosed in 4981 (10%) and 1080 (5%) patients in Scotland and Sweden, respectively. At 1 year, 720 (15%) and 112 (10%) patients died with an AUC for the GRACE 2.0 score of 0.83 [95% confidence interval (CI) 0.82–0.85] and 0.85 (95% CI 0.81–0.89). Type 2 myocardial infarction occurred in 1121 (2%) and 247 (1%) patients in Scotland and Sweden, respectively, with 258 (23%) and 57 (23%) deaths at 1 year. The AUC was 0.73 (95% CI 0.70–0.77) and 0.73 (95% CI 0.66–0.81) in type 2 myocardial infarction, which was lower than for type 1 myocardial infarction in both cohorts (P < 0.001 and P = 0.008, respectively).

Conclusion

The GRACE 2.0 score provided good discrimination for all-cause death at 1 year in patients with type 1 myocardial infarction, and moderate discrimination for those with type 2 myocardial infarction.

Trial registration

ClinicalTrials.gov number, NCT01852123.
Unraveling the regulation of sophorolipid biosynthesis in Starmerella bombicola
Authors: Lodens Sofie , Roelants Sophie L K W , Luyten Goedele , Geys Robin , Coussement Pieter , De Maeseneire Sofie L , Soetaert Wim
Published: April 2020

Starmerella bombicola very efficiently produces the secondary metabolites sophorolipids (SLs). Their biosynthesis is not-growth associated and highly upregulated in the stationary phase. Despite high industrial and academic interest, the underlying regulation of SL biosynthesis remains unknown. In this paper, potential regulation of SL biosynthesis through the telomere positioning effect (TPE) was investigated, as the SL gene cluster is located adjacent to a telomere. An additional copy of this gene cluster was introduced elsewhere in the genome to investigate if this results in a decoy of regulation. Indeed, for the new strain, the onset of SL production was shifted to the exponential phase. This result was confirmed by RT-qPCR analysis. The TPE effect was further investigated by developing and applying a suitable reporter system for this non-conventional yeast, enabling non-biased comparison of gene expression between the subtelomeric CYP52M1- and the URA3 locus. This was done with a constitutive endogenous promotor (pGAPD) and one of the endogenous promotors of the SL biosynthetic gene cluster (pCYP52M1). A clear positioning effect was observed for both promotors with significantly higher GFP expression levels at the URA3 locus. No clear GFP upregulation was observed in the stationary phase for any of the new strains.
Shadow Economies and the Success of Economic Sanctions: Explaining Why Democratic Targets Are Disadvantaged
Authors: Early Bryan R , Peksen Dursun
Published: April 2020

The sanctions literature has identified numerous mechanisms by which the adverse economic effects of sanctions impact their success rate. This body of work, however, has mostly focused on targets’ formal economies and has thus overlooked whether sanctions-induced changes in shadow (also known as informal) economic activity influence sanctions’ effectiveness. In this article, we develop two rival arguments that can potentially explain how shadow sector growth affects sanctions’ outcomes. Our grievance mitigation theory argues that increased shadow sector activity decreases the political pressure on leaders to capitulate to sanctions, while our disadvantaged democracy theory asserts that shadow economies create budgetary resource demands and deficits that disproportionately hamper democratic targets’ ability to resist sanctions. We assess the empirical merits of the two theories using time-series cross-national data for 1950–2005. We find robust evidence that the growth of shadow economies increases the likelihood of sanctions’ success in democratic targets while not significantly affecting the success rate of sanctions against non-democratic regimes. Our findings shed new light on the processes by which the economic disruptions and hardships created by sanctions translate into pressure on targeted regimes to concede to sanctions.
Winning Hearts and Minds with Economic Sanctions? Evidence from a Survey Experiment in Venezuela
Authors: Sejersen Mikkel
Published: April 2020

Previous research contends that economic sanctions must benefit opposition groups relative to the incumbent regime in order to generate policy change. However, studies have found that sanctions often backfire and increase regime support. While this rally-around-the-flag effect is well known, it is currently unclear how senders can prevent it. In this article, I use individual-level data from a targeted state to examine whether a sender's framing of the sanctions may play a role in preventing the rally-around-the-flag effect. A survey experiment conducted among respondents in Venezuela demonstrates that the public attitude toward sanctions is shaped by the framing of the sanctions. Specifically, people adopt more favorable views when interpreting sanctions as targeted measures against regime members with the explicit goal of protecting fundamental human rights. The effects are evident among moderates, which is significant as they are otherwise the group most likely to rally behind the regime.
Fluid pressure diffusion effects on the excess compliance matrix of porous rocks containing aligned fractures
Authors: Castromán Gabriel A , Barbosa Nicolás D , Rubino J Germán , Zyserman Fabio I , Holliger Klaus
Published: April 2020

The presence of sets of open fractures is common in most reservoirs, and they exert important controls on the reservoir permeability as fractures act as preferential pathways for fluid flow. Therefore, the correct characterization of fracture sets in fluid-saturated rocks is of great practical importance. In this context, the inversion of fracture characteristics from seismic data is promising since their signatures are sensitive to a wide range of pertinent fracture parameters, such as density, orientation and fluid infill. The most commonly used inversion schemes are based on the classical linear slip theory (LST), in which the effects of the fractures are represented by a real-valued diagonal excess compliance matrix. To account for the effects of wave-induced fluid pressure diffusion (FPD) between fractures and their embedding background, several authors have shown that this matrix should be complex-valued and frequency-dependent. However, these approaches neglect the effects of FPD on the coupling between orthogonal deformations of the rock. With this motivation, we considered a fracture model based on a sequence of alternating poroelastic layers of finite thickness representing the background and the fractures, and derived analytical expressions for the corresponding excess compliance matrix. We evaluated this matrix for a wide range of background parameters to quantify the magnitude of its coefficients not accounted for by the classical LST and to determine how they are affected by FPD. We estimated the relative errors in the computation of anisotropic seismic velocity and attenuation associated with the LST approach. Our analysis showed that, in some cases, considering the simplified excess compliance matrix may lead to an incorrect representation of the anisotropic response of the probed fractured rock.
Data-driven and machine learning identification of seismic reference stations in Europe
Authors: Pilz Marco , Cotton Fabrice , Kotha Sreeram Reddy
Published: April 2020

The growing seismic networks and the increasing number of permanent seismic stations can help in improving the physical basis of seismic hazard assessment. For this purpose, the definition of reference site conditions is of great significance. If a reliable estimate of the reference ground motion is known, its modification at any given site can be modelled with respect to that reference site. Since the choice of a well-characterized reference site is not straightforward, mainly due to the high variability in the shallow layers, such choices prove to be affected by large uncertainties. While proxy parameters like the average S-wave velocity over the uppermost 30 m (vS30) might help in characterizing reference site conditions, such parameters are neither available at all sites nor do they allow concluding that the site is not affected by amplification and attenuation effects. In this study, we identify prospective reference sites across Europe in a harmonized and fully data-driven way. All analysis is based on freely available geological and geophysical data and no on-site measurements or site-specific proxies are required. The study accounts for both the influence of amplification and attenuation in a large frequency range. To address the key conceptual issues, we verify our classification based on machine learning techniques in which the influence of the individual site characterization parameters is investigated. Our study indicates that around 250 sites in Europe over more than 2000 investigated are not affected by local site effects and can de facto be considered as reference sites based on the criteria applied.
Relationship between birth weight and chronic kidney disease: evidence from systematics review and two-sample Mendelian randomization analysis
Authors: Yu Xinghao , Yuan Zhongshang , Lu Haojie , Gao Yixin , Chen Haimiao , Shao Zhonghe , Yang Jiaji , Guan Fengjun , Huang Shuiping , Zeng Ping
Published: April 2020

Observational studies showed an inverse association between birth weight and chronic kidney disease (CKD) in adulthood existed. However, whether such an association is causal remains fully elusive. Moreover, none of prior studies distinguished the direct fetal effect from the indirect maternal effect. Herein, we aimed to investigate the causal relationship between birth weight and CKD and to understand the relative fetal and maternal contributions. Meta-analysis (n = ~22 million) showed that low birth weight led to ~83% (95% confidence interval [CI] 37–146%) higher risk of CKD in late life. With summary statistics from large scale GWASs (n = ~300 000 for birth weight and ~481 000 for CKD), linkage disequilibrium score regression demonstrated birth weight had a negative maternal, but not fetal, genetic correlation with CKD and several other kidney-function related phenotypes. Furthermore, with multiple instruments of birth weight, Mendelian randomization showed there existed a negative fetal casual association (OR = 1.10, 95% CI 1.01–1.16) between birth weight and CKD; a negative but non-significant maternal casual association (OR = 1.09, 95% CI 0.98–1.21) was also identified. Those associations were robust against various sensitivity analyses. However, no maternal/fetal casual effects of birth weight were significant for other kidney-function related phenotypes. Overall, our study confirmed the inverse association between birth weight and CKD observed in prior studies, and further revealed the shared maternal genetic foundation between low birth weight and CKD, and the direct fetal and indirect maternal causal effects of birth weight may commonly drive this negative relationship.
Adaption potential of Crassostrea gigas to ocean acidification and disease caused by Vibrio harveyi
Authors: Nordio Davide , Khtikian Natalie , Andrews Sean , Bertotto Daniela , Leask Karen , Green Timothy
Published: April 2020

The survival and development of bivalve larvae is adversely impacted by ocean acidification and Vibrio infection, indicating that bivalves need to simultaneously adapt to both stressors associated with anthropogenic climate change. In this study, we use a half-dial breeding design to estimate heritability (h2) for survival to Vibrio harveyi infection and larval shell length to aragonite undersaturated and normal conditions in laboratory-reared Crassostrea gigas. Phenotypic differences were observed between families for these traits with heritability estimated to be moderate for survival to V. harveyi challenge (h2 = 0.25) and low for shell length in corrosive (Ωaragonite = 0.9, h2 = 0.15) and normal conditions (Ωaragonite = 1.6, h2 = 0.15). Predicted breeding values for larval shell length are correlated between aragonite-undersaturated and normal conditions (Spearman r = 0.63, p < 0.05), indicating that larger larvae tend to do better in corrosive seawater. Aquaculture hatcheries routinely cull slow-growing larvae to reduce and synchronize time taken for larvae to metamorphose to spat, thus inadvertently applying size-related selection for larger larvae. This indirect selection in the hatchery populations provides a plausible explanation why domesticated oyster populations are less sensitive to ocean acidification.
When past is not a prologue: Adapting informatics practice during a pandemic
Authors: Kannampallil Thomas G , Foraker Randi E , Lai Albert M , Woeltje Keith F , Payne Philip R O
Published: April 2020

Data and information technology are key to every aspect of our response to the current coronavirus disease 2019 (COVID-19) pandemic—including the diagnosis of patients and delivery of care, the development of predictive models of disease spread, and the management of personnel and equipment. The increasing engagement of informaticians at the forefront of these efforts has been a fundamental shift, from an academic to an operational role. However, the past history of informatics as a scientific domain and an area of applied practice provides little guidance or prologue for the incredible challenges that we are now tasked with performing. Building on our recent experiences, we present 4 critical lessons learned that have helped shape our scalable, data-driven response to COVID-19. We describe each of these lessons within the context of specific solutions and strategies we applied in addressing the challenges that we faced.
Excessively activated plasminogen in human plasma cleaves VWF multimers and reduces collagen-binding activity
Authors: Togashi Kenshi , Suzuki Satoshi , Morita Sae , Ogasawara Yuki , Imamura Yasutada , Shin Yongchol
Published: April 2020

Plasmin (Pm) is a serine protease that can dissolve fibrin clots. Several possible functions of Pm in blood other than fibrinolysis have been proposed. To explore the effects of Pm on primary haemostasis, we evaluated the cleavage of von Willebrand factor multimers (VWFMs) in human plasma by streptokinase (SK)-activated plasminogen (Pg) and the binding ability of the digested VWFMs to collagen. SK-activated Pg and ADAMTS13 (a VWF-cleaving enzyme) in human plasma cleaved VWFMs in conformation-dependent manners through dialysis to the urea-containing buffer. However, VWFMs in human plasma under vortex-based shear stress were cleaved by SK-activated Pg but not by ADAMTS13. These results suggested that the VWFM-cleavage sites in human plasma are exposed to some extent by vortex-based shear stress for Pm but not for ADAMTS13. Additionally, we revealed that cleavage by SK-activated Pg reduced VWFMs’ binding ability to collagen, and VWFMs in human plasma were cleaved by Pm at several sites. These results suggest that SK-activated Pg degrades VWFMs, reduces their binding abilities to collagen and affects primary haemostasis. Because excessive Pg activation can degrade fibrinogen/fibrin, we propose that SK-activated Pg in blood may cause impaired primary and secondary haemostasis.