bluuebunny/crossref_metadata_2025 huggingface dataset:
Lysosomal storage disease spectrum in nonimmune hydrops fetalis: a retrospective case control study
Authors: Al‐Kouatly Huda B. , Felder Laura , Makhamreh Mona M. , Kass Stephanie L. , Vora Neeta L. , Berghella Vincenzo , Berger Seth , Wenger David A. , Luzi Paola
Published: March 2020

Objectives

Nonimmune hydrops fetalis (NIHF) accounts for 90% of hydrops fetalis cases. About 15% to 29% of unexplained NIHF cases are caused by lysosomal storage diseases (LSD). We review the spectrum of LSD and associated clinical findings in NIHF in a cohort of patients referred to our institution.

Methods

We present a retrospective case‐control study of cases with NIHF referred for LSD biochemical testing at a single center. Cases diagnosed with LSD were matched to controls with NIHF and negative LSD testing and analyzed according to the STROBE criteria to the extent the retrospective nature of this study allowed.

Results

Between January 2006 and December 2018, 28 patients with NIHF were diagnosed with a LSD. Eight types of LSD were diagnosed: galactosialidosis 8/28 (28.6%), sialic acid storage disease (SASD) 5/28 (17.9%), mucopolysaccharidosis VII 5/28 (17.9%), Gaucher 4/28 (14.3%), sialidosis 2/28 (7.1%), GM1 gangliosidosis 2/28 (7.1%), Niemann‐Pick disease type C 1/28 (3.6%), and mucolipidosis II/III 1/28 (3.6%). Associated clinical features were hepatomegaly 16/21 (76.2%) vs 22/65 (33.8%), P < .05, splenomegaly 12/20 (60.0%) vs 14/58 (24.1%), P < .05, and hepatosplenomegaly 10/20 (50.0%) vs 13/58 (22.4%) P < .05.

Conclusion

The most common LSD in NIHF were galactosialidosis, SASD, mucopolysaccharidosis VII, and Gaucher disease. LSD should be considered in unexplained NIHF cases, particularly if hepatomegaly, splenomegaly, or hepatosplenomegaly is visualized on prenatal ultrasound.
Empirical assessment of case‐based methods for drug safety alert identification in the French National Healthcare System database (SNDS): Methodology of the ALCAPONE project
Authors: Thurin Nicolas H. , Lassalle Régis , Schuemie Martijn , Pénichon Marine , Gagne Joshua J. , Rassen Jeremy A. , Benichou Jacques , Weill Alain , Blin Patrick , Moore Nicholas , Droz‐Perroteau Cécile
Published: March 2020

Objectives

To introduce the methodology of the ALCAPONE project.

Background

The French National Healthcare System Database (SNDS), covering 99% of the French population, provides a potentially valuable opportunity for drug safety alert generation. ALCAPONE aimed to assess empirically in the SNDS case‐based designs for alert generation related to four health outcomes of interest.

Methods

ALCAPONE used a reference set adapted from observational medical outcomes partnership (OMOP) and Exploring and Understanding Adverse Drug Reactions (EU‐ADR) project, with four outcomes—acute liver injury (ALI), myocardial infarction (MI), acute kidney injury (AKI), and upper gastrointestinal bleeding (UGIB)—and positive and negative drug controls. ALCAPONE consisted of four main phases: (1) data preparation to fit the OMOP Common Data Model and select the drug controls; (2) detection of the selected controls via three case‐based designs: case‐population, case‐control, and self‐controlled case series, including design variants (varying risk window, adjustment strategy, etc.); (3) comparison of design variant performance (area under the ROC curve, mean square error, etc.); and (4) selection of the optimal design variants and their calibration for each outcome.

Results

Over 2009‐2014, 5225 cases of ALI, 354 109 MI, 12 633 AKI, and 156 057 UGIB were identified using specific definitions. The number of detectable drugs ranged from 61 for MI to 25 for ALI. Design variants generated more than 50 000 points estimates. Results by outcome will be published in forthcoming papers.

Conclusions

ALCAPONE has shown the interest of the empirical assessment of pharmacoepidemiological approaches for drug safety alert generation and may encourage other researchers to do the same in other databases.
Mitochondrial Dysfunction in Age‐Related Metabolic Disorders
Authors: Natarajan Venkateswaran , Chawla Ritu , Mah Tania , Vivekanandan Rajesh , Tan Shu Yi , Sato Priscila Y , Mallilankaraman Karthik
Published: March 2020

Aging is a natural biological process in living organisms characterized by receding bioenergetics. Mitochondria are crucial for cellular bioenergetics and thus an important contributor to age‐related energetics deterioration. In addition, mitochondria play a major role in calcium signaling, redox homeostasis, and thermogenesis making this organelle a major cellular component that dictates the fate of a cell. To maintain its quantity and quality, mitochondria undergo multiple processes such as fission, fusion, and mitophagy to eliminate or replace damaged mitochondria. While this bioenergetics machinery is properly protected, the functional decline associated with age and age‐related metabolic diseases is mostly a result of failure in such protective mechanisms. In addition, metabolic by‐products like reactive oxygen species also aid in this destructive pathway. Mitochondrial dysfunction has always been thought to be associated with diseases. Moreover, studies in recent years have pointed out that aging contributes to the decay of mitochondrial health by promoting imbalances in key mitochondrial‐regulated pathways. Hence, it is crucial to understand the nexus of mitochondrial dysfunction in age‐related diseases. This review focuses on various aspects of basic mitochondrial biology and its status in aging and age‐related metabolic diseases.
A Zwitterionic Compound with Heterocyclic Ions as Promising Heat‐Resistant Explosive
Authors: Li Chuan , Deng Chenglong , Zhao Baojing , Wang Min , Zhang Man , Zhou Zhiming
Published: March 2020

A unique zwitterionic compound consisting of functionalized pyrazolate and triazolium ions was synthesized and characterized fully. The zwitterionic compound, 3,5‐dinitro‐4‐(3,4,5‐triamino‐4H‐1,2,4‐triazol‐1‐ium‐1‐yl)‐4H‐pyrazol‐4‐ide (CPTY, 3), exhibits superhigh heat resistance, has a decomposition temperature of 335 °C, and is insensitive to impact and friction. In addition, owing to its high density (1.82 g cm−3) and positive heat of formation (555.9 kJ mol−1), its detonation velocity and pressure are acceptable high at 8750 m s−1 and 31.5 GPa, respectively. The highly attractive physicochemical and detonation properties of 3 make it promising for use as a heat‐resistant explosive.
Prognostic value of an inflammatory index for patients with metastatic castration‐resistant prostate cancer
Authors: Yamada Yasutaka , Sakamoto Shinichi , Rii Junryo , Yamamoto Satoshi , Kamada Shuhei , Imamura Yusuke , Nakamura Kazuyoshi , Komiya Akira , Nakatsu Hiroomi , Ichikawa Tomohiko
Published: March 2020

Background

The inflammatory process has been reported to be involved in the formation and progression of various types of cancer. Recently, a peripheral inflammatory index, combining the derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and the lactate dehydrogenase (LDH) level, was proposed as a useful prognostic marker in advanced nonsmall cell lung cancer. The prognostic value of inflammatory markers in prostate cancer has not been established. We aimed to validate the prognostic significance of this peripheral inflammatory index in metastatic castration‐resistant prostate cancer (mCRPC).

Methods

Clinical data of 196 mCRPC patients were retrospectively collected from multiple institutions. Clinical factors and inflammatory markers at the development of CRPC, including white blood cell count, absolute neutrophil count, dNLR, neutrophil‐lymphocyte ratio, platelet‐lymphocyte ratio, C‐reactive protein (CRP), and LDH levels, were evaluated. The patients were classified into three groups based on the inflammatory index: Good (low dNLR and LDH), Intermediate (high dNLR or LDH), and Poor (high dNLR and LDH). Overall survival (OS) and cancer‐specific survival after CRPC were analyzed using Cox proportional hazard models and Kaplan‐Meier methods.

Results

The median age and baseline prostate‐specific antigen level were 75 years and 397.15 ng/mL, respectively. On multivariate analysis, dNLR (≥1.51; hazard ratio [HR] = 1.624;P = .0173), LDH (≥upper limit of normal; HR = 2.065;P = .0004), alkaline phosphatase (≥310 U/L; HR = 2.546;P < .0001), and positive N stage (HR = 1.621;P = .048) were associated with poor OS after CRPC, whereas other inflammatory markers including the NLR were not. The Good inflammatory index group showed significantly longer OS after CRPC compared to the Intermediate and Poor groups, with median survivals of 46.2, 28.9, and 16.6 months, respectively.

Conclusions

The novel inflammatory index combining dNLR and LDH was a useful prognostic parameter in patients with mCRPC. Our analysis suggested that dNLR emerged as a more valuable prognostic marker than NLR.
Z‐ligustilide: A review of its pharmacokinetics and pharmacology
Authors: Xie Qingxuan , Zhang Linlin , Xie Long , Zheng Yu , Liu Kai , Tang Hailong , Liao Yanmei , Li Xiaofang
Published: March 2020

Z‐ligustilide is a natural benzoquinone derivative found in many widely used Chinese herbal medicines such as Angelica sinensis (Oliv.) Diels as well as Ligusticum chuanxiong Hort and so on. It has been used as a part of traditional Chinese medicine and is also present in various Chinese medicine preparations. Pharmacokinetic studies have shown that Z‐ligustilide has poor oral bioavailability in rats due to severe first‐pass metabolic reactions. New evidence suggests that Z‐ligustilide has a wide range of pharmacological properties, including anticancer, antiinflammatory, anti‐oxidant as well as neuroprotective activities and so on. The literature discussed is derived from readily accessible papers spanning the early 1970s to the end of March 2019. Information were collected from journals, books, and online searches (Google Scholar, PubMed, Science Direct, Science Citation Index Finder, Springer link, and CNKI). This review intends to provide a comprehensive overview of the pharmacokinetics and pharmacology of Z‐ligustilide in recent years, with a focus on its biological properties and mechanisms, which is of great significance for Chinese medicine.
State and mode feedback control strategy for discrete‐time Markovian jump linear systems with time‐varying controllable mode transition probability matrix
Authors: Zhu Jin , Wu Xinghua , Li Chaoxiang , Dullerud Geir E.
Published: March 2020

In this article, the state and mode feedback control strategy is investigated for the discrete‐time Markovian jump linear system (MJLS) with time‐varying controllable mode transition probability matrix (MTPM). This strategy, consisting of a state feedback controller and a mode feedback controller, is proposed to ensure MJLS's stability and meanwhile improve system performance. First, a mode‐dependent state feedback controller is designed to stabilize the MJLS based on the time‐invariant part of the MTPM such that it can still keep valid even if the MTPM is adjusted by the mode feedback control. Second, a generalized quadratic stabilization cost is put forward for evaluating MJLS's performance, which contains system state, state feedback controller, and mode feedback controller. To reduce the stabilization cost, a mode feedback controller is introduced to adjust each mode's occurrence probability by changing the time‐varying controllable part of MTPM. The calculation of such mode feedback controller is given based on a value‐iteration algorithm with its convergence proof. Compared with traditional state feedback control strategy, this state and mode feedback control strategy offers a new perspective for the control problem of general nonhomogeneous MJLSs. Numerical examples are provided to illustrate the validity of the proposed strategy.
Hydrothermal Synthesis of Humate‐Layer‐Based Bimetal Organic Framework Composites as High Rate‐Capability and Enery‐Density Electrode Materials for Supercapacitors
Authors: Wang Xiaoqin , Yang Nana , Li Qiaoqin , He Fan , Yang Yufei , Cong Shaoling , Li Kanshe , Xiong Shanxin , Zhou Anning
Published: March 2020

A humate‐layer‐based bimetal organic framework (HA‐NiCo‐BPDC) material is successfully synthesized using humate layers obtained by ultrasonic‐hydrothermal peeling as a substrate and BPDC as a ligand via a hydrothermal approach. It exhibits a porous composite structure in which flower‐like NiCo‐BPDC nanosheets are loaded on humate layers, originating a guiding effect of humate layers on the NiCo‐BPDC growth. HA‐NiCo‐BPDC owns a similar crystal structure to NiCo‐BPDC, in which humate and BPDC ions have coordinated with nickel or cobalt ions to form carboxylates. Nickel and cobalt ions present positive divalent states, and they have close ability to coordinate with BPDC or humate ions. Owing to unique hierarchical architectures and fascinating synergetic effects between NiCo‐BPDC nanosheets and humate layers, HA‐NiCo‐BPDC has high specific capacitance and rate capability, and low internal resistance and charge transfer resistance. It exhibits better rate capability than NiCo‐BPDC and larger specific capacitance than HA−Ni(Co)‐BPDC. Moreover, HA‐NiCo‐BPDC//rGO asymmetric supercapacitor has wide operating potential window, high energy density and cycling stability. All those show that HA‐NiCo‐BPDC composites are a promising electrode material for supercapacitors. This study exploits a novel way for value‐added applications of humates and their natural sources “humic acids”.
Detecting Stuxnet‐like data integrity attacks
Authors: Tuuli Siiskonen , Mika Rantonen
Published: March 2020

This work suggests and tests a solution for detecting loss of integrity with means of prediction in distributed, low‐power computing environment or when collecting relational data disconnected from original data source to data ecosystems. With graph convolution network and variational auto‐encoder, the proposed solution is able to detect data integrity attacks based on link prediction for datasets from various data sources without common data model. The solution has in‐built mechanism to prevent poisoning the detection capability, and it is resource efficient since it does not require extensive storage capability. Due to its programmatic nature and high ability to integrate, unsupervised learning‐based solution fits well in embedded system ecosystems' control functions where automated decisions are taken.
Probing dark matter freeze-in with long-lived particle signatures: MATHUSLA, HL-LHC and FCC-hh
Authors: No J.M. , Tunney P. , Zaldivar B.
Published: March 2020

Abstract

Collider searches for long-lived particles yield a promising avenue to probe the freeze-in production of Dark Matter via the decay of a parent particle. We analyze the prospects of probing the parameter space of Dark Matter freeze-in from the decay of neutral parent particles at the LHC and beyond, taking as a case study a freeze-in Dark Matter scenario via the Standard Model Higgs. We obtain the projected sensitivity of the proposed MATHUSLA surface detector (for MATHUSLA100 and MATHUSLA200 configurations) for long-lived particle searches to the freeze-in Dark Matter parameter space, and study its complementarity to searches by ATLAS and CMS at HL-LHC, as well as the interplay with constraints from Cosmology: Big-Bang Nucleosynthesis and Lyman-α forest observations. We then analyze the improvement in sensitivity that would come from a forward detector within a future 100 TeV pp-collider. In addition, we discuss several technical aspects of the present Dark Matter freeze-in scenario: the role of the electroweak phase transition; the inclusion of thermal masses, which have been previously disregarded in freeze-in from decay studies; the impact of 2 → 2 scattering processes on the Dark Matter relic abundance; and the interplay between freeze-in and super-WIMP Dark Matter production mechanisms.
Risk factors of non-union in intramedullary stabilized diaphyseal long bone fractures: identifying the role of fracture stabilization strategies and concomitant injuries
Authors: Hofman Martijn , Andruszkow Hagen , Heyer Frans L. , Kobbe Philipp , Hildebrand Frank , Poeze Martijn
Published: March 2020

Purpose

Concomitant chest injury is known to negatively affect bone metabolism and fracture healing, whereas traumatic brain injury (TBI) appears to have positive effects on bone metabolism. Osteogenesis can also be influenced by the timing of fracture stabilization. We aimed to identify how chest injuries, TBI and fracture stabilization strategy influences the incidence of non-union.

Methods

Patients with long bone fractures of the lower extremities who had been treated between 2004 and 2014 were retrospectively analysed. Non-union was defined as fracture healing not occurring in the expected time period and in which neither progression of healing nor successful union is expected without intervention. Diverse clinical and radiological parameters were statistically analysed using the Statistical Package for the Social Sciences (SPSS).

Results

The total number of operations before consolidation was an independent predictor (odds ratio [OR] = 6.416, p < 0.001) for the development of non-union in patients with long bone fractures. More specifically, patients treated according to the damage control orthopaedics (DCO) principle had a significantly higher risk of developing a non-union than patients treated according to the early total care (ETC) principle (OR = 7.878, p = 0.005). Concomitant chest injury and TBI could not be identified as influencing factors for non-union development.

Conclusion

Our results indicate that the number of operations performed in patients with long bone fractures should be kept as low as possible and that the indication for and the timing of DCO treatment should be meticulously noted to minimize the risk of non-union development.
Forecasting exports across Europe: What are the superior survey indicators?
Authors: Lehmann Robert
Published: March 2020

In this study, we systematically evaluate the potential of a bunch of survey-based indicators from different economic branches to forecasting export growth across a multitude of European countries. Our pseudo-out-of-sample analyses reveal that the best performing indicators beat a well-specified benchmark model in terms of forecast accuracy. It turns out that four indicators are superior: the Export Climate, the Production Expectations of domestic manufacturing firms, the Industrial Confidence Indicator, and the Economic Sentiment Indicator. Two robustness checks confirm these results. As exports are highly volatile and turn out to be a large demand-side component of gross domestic product, our results can be used by applied forecasters in order to choose the best performing indicators and thus increasing the accuracy of export forecasts.
Modulation of Transient Receptor Potential Channels 3 and 6 Regulates Osteoclast Function with Impact on Trabecular Bone Loss
Authors: Klein Sebastian , Mentrup Birgit , Timmen Melanie , Sherwood Joanna , Lindemann Otto , Fobker Manfred , Kronenberg Daniel , Pap Thomas , Raschke Michael J. , Stange Richard
Published: March 2020

Enhanced osteoclast formation and function is a fundamental cause of alterations to bone structure and plays an important role in several diseases impairing bone quality. Recent work revealed that TRP calcium channels 3 and 6 might play a special role in this context. By analyzing the bone phenotype of TRPC6-deficient mice we detected a regulatory effect of TRPC3 on osteoclast function. These mice exhibit a significant decrease in bone volume per tissue volume, trabecular thickness and -number together with an increased number of osteoclasts found on the surface of trabecular bone. Primary bone marrow mononuclear cells from TRPC6-deficient mice showed enhanced osteoclastic differentiation and resorptive activity. This was confirmed in vitro by using TRPC6-deficient RAW 264.7 cells. TRPC6 deficiency led to an increase of TRPC3 in osteoclasts, suggesting that TRPC3 overcompensates for the loss of TRPC6. Raised intracellular calcium levels led to enhanced NFAT-luciferase reporter gene activity in the absence of TRPC6. In line with these findings inhibition of TRPC3 using the specific inhibitor Pyr3 significantly reduced intracellular calcium concentrations and normalized osteoclastic differentiation and resorptive activity of TRPC6-deficient cells. Interestingly, an up-regulation of TRPC3 could be detected in a cohort of patients with low bone mineral density by comparing micro array data sets of circulating human osteoclast precursor cells to those from patients with high bone mineral density, suggesting a noticeable contribution of TRP calcium channels on bone quality. These observations demonstrate a novel regulatory function of TRPC channels in the process of osteoclastic differentiation and bone loss.
Nonlocal Kirchhoff Problems with Singular Exponential Nonlinearity
Authors: Mingqi Xiang , Rădulescu Vicenţiu D. , Zhang Binlin
Published: March 2020

In this paper, we first develop the fractional Trudinger–Moser inequality in singular case and then we use it to study the existence and multiplicity of solutions for a class of perturbed fractional Kirchhoff type problems with singular exponential nonlinearity. Under some suitable assumptions, the existence of two nontrivial and nonnegative solutions is obtained by using the mountain pass theorem and Ekeland’s variational principle as the nonlinear term satisfies critical or subcritical exponential growth conditions. Moreover, the existence of ground state solutions for the aforementioned problems without perturbation and without the Ambrosetti–Rabinowitz condition is investigated.
Prognostic factors for the outcome of needle aspiration of calcific deposits for rotator cuff calcific tendinitis
Authors: Oudelaar Bart W. , Huis In ‘t Veld Rianne , Schepers-Bok Relinde , Ooms Edwin M. , Nelissen Rob G. H. H. , Vochteloo Anne J. H.
Published: March 2020

Objective

To identify prognostic factors for the effectiveness of needle aspiration of calcific deposits (NACD) for rotator cuff calcific tendinitis (RCCT)

Methods

One hundred forty-nine patients with symptomatic RCCT were included in a prospective cohort study. Pain (VAS), shoulder function (SST and DASH), and quality of life (EQ-5D) were assessed at baseline and at 3, 6, and 12 months post-NACD. Univariate analyses (independent t tests or Mann-Whitney U tests depending on the distribution of data) were performed to build a multivariable linear regression model. Stepwise regression analysis through backward elimination was performed to evaluate the effect of predefined prognostic factors on the outcome.

Results

Patients who underwent multiple NACD procedures had less reduction of pain (p < 0.01). Furthermore, a larger reduction in VAS pain scores at 3 months post-NACD was associated with a larger reduction in VAS pain scores at 12 months (p < 0.01). More improvement of SST and DASH scores at 3 months was associated with better SST, DASH, and EQ-5D scores at 12 months (p < 0.01). Smaller-size calcific deposits were associated with less improvement of DASH (p = 0.03) and EQ-5D scores (p = 0.01). A longer duration of symptoms prior to NACD was associated with less improvement of EQ-5D scores (p = 0.01).

Conclusions

A good initial response after NACD is associated with better outcomes at 12 months. Patients with a longer duration of symptoms prior to NACD and patients who require multiple procedures showed inferior outcomes in terms of pain reduction and improvement of quality of life. Smaller-size calcific deposits are associated with a less favorable outcome of shoulder function and quality of life scores and might therefore be less susceptible for NACD.

Key Points

• A good initial response to NACD is associated with a better outcome in the longer term.

• A longer duration of symptoms and the need for multiple NACD procedures are associated with inferior outcomes.

• Smaller-size calcific deposits seem less susceptible for NACD.
Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review
Authors: Huber D. , Seitz S. , Kast K. , Emons G. , Ortmann O.
Published: March 2020

Purpose

BRCA mutation carriers have an increased risk of developing breast or ovarian cancer. Oral contraception (OC) is known to increase breast cancer and reduce ovarian cancer risk in the general population. This review analyses the published data on OC and risk of cancer in BRCA mutation carriers.

Methods

We included all relevant articles published in English from 1995 to 2018. Literature was identified through a search on PubMed and Cochrane Library.

Results

We included four meta-analyses, one review, one case–control study and one retrospective cohort study on the association between ovarian cancer and OC in BRCA mutation carriers. All report a risk reduction for the OC users and several also describe an inverse correlation with duration of use. Regarding breast cancer, we included four meta-analyses, one review, one case–control study, two case-only studies, one prospective and one retrospective cohort study. Some studies report a risk elevation, while others did not find an association between OC use and breast cancer in BRCA mutation carriers. In other studies, the association was limited to early-onset breast cancer and/or associated with young age at first start of OC.

Conclusion

Oral contraception leads to a risk reduction of ovarian cancer also in BRCA mutation carriers. An increase in breast cancer risk due to OC cannot be excluded. Women with BRCA mutation who consider OC use have to be informed about possible increase in breast cancer risk and alternative contraceptive methods. OC should not be used for the prevention of ovarian cancer in this population.
CT angiography vs echocardiography for detection of cardiac thrombi in ischemic stroke: a systematic review and meta-analysis
Authors: Groeneveld Nina-Suzanne , Guglielmi Valeria , Leeflang Mariska M. G. , Matthijs Boekholdt S. , Nils Planken R. , Roos Yvo B. W. E. M. , Majoie Charles B. L. M. , Coutinho Jonathan M.
Published: March 2020

Background and purpose

Cardiac thrombi are an important cause of embolic stroke. We studied the diagnostic yield and diagnostic accuracy of cardiac CT angiography (CTA) compared to echocardiography for detection of cardiac thrombi in ischemic stroke patients.

Methods

We performed a systematic review and meta-analysis of the literature on cardiac CTA versus echocardiography for detection of cardiac thrombi in ischemic stroke patients. We included studies (N ≥ 20) in which both cardiac CTA (index test) and echocardiography (reference test) were performed and data on cardiac thrombi were reported. Results were stratified for type of echocardiography: transesophageal (TEE) vs transthoracic (TTE).

Results

Out of 1530 studies, 14 were included (all single center cohort studies), with data on 1568 patients. Mean age varied between 52 and 69 years per study and 66% were men. Reported time intervals ranged from 0 to 21 days between stroke and first test, and from 0 to 199 days between tests. In ten studies that compared CTA to TEE, CTA detected cardiac thrombi in 87/1385 (6.3%) patients versus 68/1385 (4.9%) on TEE (p < 0.001). In four studies comparing CTA to TTE, CTA detected thrombi in 23/183 (12.5%) patients versus 12/183 (6.6%) on TTE (p = 0.010). Pooled sensitivity and specificity of CTA versus TEE were 86.0% (95% CI 65.6–95.2) and 97.4% (95% CI 95.0–98.7), respectively.

Conclusions

CTA may be a promising alternative to echocardiography for detection of cardiac thrombi in patients with ischemic stroke, especially now that CTA is standard care for patient selection for endovascular treatment. However, studies were too heterogeneous and of insufficient methodological quality to draw firm conclusions. Large, prospective studies on this topic are warranted.
The burden of high workload on the health-related quality of life among home care workers in Northern Sweden
Authors: Sjöberg André , Pettersson-Strömbäck Anita , Sahlén Klas-Göran , Lindholm Lars , Norström Fredrik
Published: March 2020

Objective

Previous studies have shown that high workload affects health negatively. However, studies are lacking among home care workers. The aim of this study is to examine the burden of perceived workload on health-related quality of life (HRQoL) among home care workers and to determine whether psychosocial factors modify such a relationship.

Methods

A cross-sectional study was conducted in which 1162 (58% response rate) home care workers participated. The psychosocial factors were measured by QPSnordic. HRQoL was measured by EuroQol 5 dimensions, from which responses were translated into quality-adjusted life year scores (QALY). Propensity scores were used with absolute risk differences (RD). Stratified analysis was used to test the buffer hypothesis of the demand–control–support model.

Results

Personnel with a high workload had a statistically significant 0.035 lower QALY than personnel with a normal workload. This difference was also statistically significant for the Visual Analogue Scale (RD 5.0) and the mobility (RD 0.033) and anxiety/depression scales (RD 0.20) dimensions of EQ-5D. For QALY, the effect of a high workload compared to a normal workload was higher, with low (RD 0.045, significant) compared with high (RD 0.015, non-significant) social support; while it was similar, and non-significant results, for low and high control.

Conclusions

Our study shows that lowered work burden would be beneficial for home care personnel. Furthermore, our results suggest that interventions aimed at increasing social support could reduce work-related illness.
Inter-slice leakage and intra-slice aliasing in simultaneous multi-slice echo-planar images
Authors: McNabb Carolyn Beth , Lindner Michael , Shen Shan , Burgess Laura Grace , Murayama Kou , Johnstone Tom
Published: March 2020

Simultaneous multi-slice (SMS) imaging is a popular technique for increasing acquisition speed in echo-planar imaging (EPI) fMRI. However, SMS data are prone to motion sensitivity and slice leakage artefacts, which spread signal between simultaneously acquired slices. Relevant to motion sensitivity, artefacts from moving anatomic structures propagate along the phase-encoding (PE) direction. This is particularly relevant for eye movement. As signal from the eye is acquired along with signal from simultaneously excited slices during SMS, there is potential for signal to spread in-plane and between spatially remote slices. After identifying an artefact temporally coinciding with signal fluctuations in the eye and spatially distributed in correspondence with multiband slice acceleration and parallel imaging factors, we conducted a series of small experiments to investigate eye movement artefacts in SMS data and the contribution of PE direction to the invasiveness of these artefacts. Five healthy adult volunteers were scanned during a blinking task using a standard SMS-EPI protocol with posterior-to-anterior (P ≫ A), anterior-to-posterior (A ≫ P) or right-to-left (R ≫ L) PE direction. The intensity of signal fluctuations (artefact severity) was measured at expected artefact positions and control positions. We demonstrated a direct relationship between eye movements and artefact severity across expected artefact regions. Within-brain artefacts were apparent in P ≫ A- and A ≫ P-acquired data but not in R ≫ L data due to the shift in artefact positions. Further research into eye motion artefacts in SMS data is warranted but researchers should exercise caution with SMS protocols. We recommend rigorous piloting of SMS protocols and switching to R ≫ L/L ≫ R PE where feasible.
Enhancing glutaric acid production in Escherichia coli by uptake of malonic acid
Authors: Sui Xue , Zhao Mei , Liu Yingli , Wang Jing , Li Guohui , Zhang Xiaojuan , Deng Yu
Published: March 2020

Glutaric acid is an important organic acid applied widely in different fields. Most previous researches have focused on the production of glutaric acid in various strains using the 5-aminovaleric acid (AMV) or pentenoic acid synthesis pathways. We previously utilized a five-step reversed adipic acid degradation pathway (RADP) in Escherichia coli BL21 (DE3) to construct strain Bgl146. Herein, we found that malonyl-CoA was strictly limited in this strain, and increasing its abundance could improve glutaric acid production. We, therefore, constructed a malonic acid uptake pathway in E. coli using matB (malonic acid synthetase) and matC (malonic acid carrier protein) from Clover rhizobia. The titer of glutaric acid was improved by 2.1-fold and 1.45-fold, respectively, reaching 0.56 g/L and 4.35 g/L in shake flask and batch fermentation following addition of malonic acid. Finally, the highest titer of glutaric acid was 6.3 g/L in fed-batch fermentation at optimized fermentation conditions.
Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma
Authors: Wick Antje , Desjardins Annick , Suarez Cristina , Forsyth Peter , Gueorguieva Ivelina , Burkholder Tiana , Cleverly Ann Louise , Estrem Shawn T. , Wang Shuaicheng , Lahn Michael M. , Guba Susan C. , Capper David , Rodon Jordi
Published: March 2020

Purpose Galunisertib, a TGF-β inhibitor, has demonstrated antitumor effects in preclinical and radiographic responses in some patients with malignant glioma. This Phase 1b/2a trial investigated the clinical benefit of combining galunisertib with temozolomide-based radiochemotherapy (TMZ/RTX) in patients with newly diagnosed malignant glioma (NCT01220271). Methods This is an open-label, 2-arm Phase 1b/2a study (N = 56) of galunisertib (intermittent dosing: 14 days on/14 days off per cycle of 28 days) in combination with TMZ/RTX (n = 40), versus a control arm (TMZ/RTX, n = 16). The primary objective of Phase 1b was to determine the safe and tolerable Phase 2 dose of galunisertib. The primary objective of Phase 2a was to confirm the tolerability and pharmacodynamic profile of galunisertib with TMZ/RTX, and the secondary objectives included determining the efficacy and pharmacokinetic (PK) profile of galunisertib with TMZ/RTX in patients with glioblastoma. This study also characterized the changes in the major T-cell subsets during TMZ/RTX plus galunisertib treatment. Results In the Phase 2a study, efficacy results for patients treated with galunisertib plus TMZ/RTX or TMZ/RTX were: median overall survival (18.2 vs 17.9 months), median progression-free survival (7.6 vs 11.5 months), and disease control rate (80% [32/40] vs 56% [9/16] patients) respectively. PK profile of galunisertib plus TMZ/RTX regimen was consistent with previously published PK data of galunisertib. The overall safety profile across treatment arms was comparable. Conclusion No differences in efficacy, safety or pharmacokinetic variables were observed between the two treatment arms.
Identifying typical trajectories in longitudinal data: modelling strategies and interpretations
Authors: Herle Moritz , Micali Nadia , Abdulkadir Mohamed , Loos Ruth , Bryant-Waugh Rachel , Hübel Christopher , Bulik Cynthia M. , De Stavola Bianca L.
Published: March 2020

Individual-level longitudinal data on biological, behavioural, and social dimensions are becoming increasingly available. Typically, these data are analysed using mixed effects models, with the result summarised in terms of an average trajectory plus measures of the individual variations around this average. However, public health investigations would benefit from finer modelling of these individual variations which identify not just one average trajectory, but several typical trajectories. If evidence of heterogeneity in the development of these variables is found, the role played by temporally preceding (explanatory) variables as well as the potential impact of differential trajectories may have on later outcomes is often of interest. A wide choice of methods for uncovering typical trajectories and relating them to precursors and later outcomes exists. However, despite their increasing use, no practical overview of these methods targeted at epidemiological applications exists. Hence we provide: (a) a review of the three most commonly used methods for the identification of latent trajectories (growth mixture models, latent class growth analysis, and longitudinal latent class analysis); and (b) recommendations for the identification and interpretation of these trajectories and of their relationship with other variables. For illustration, we use longitudinal data on childhood body mass index and parental reports of fussy eating, collected in the Avon Longitudinal Study of Parents and Children.
Posing New Researchable Questions as a Dynamic Process in Educational Research
Authors: Stylianides Gabriel J. , Stylianides Andreas J.
Published: March 2020

In this paper, we argue that posing new researchable questions in educational research is a dynamic process that reflects the field’s growing understanding of the web of potentially influential factors surrounding the examination of a particular phenomenon of interest. We illustrate this thesis by drawing on a strand of mathematics education research related to students’ justification schemes that has evolved rapidly during the past few decades. Also, we reflect on the possible boundaries of the domain of application of the thesis, and we hypothesize that it would apply equally to other strands of educational research. To support this hypothesis, we briefly consider how the thesis would be applicable in two additional research strands. We conclude by elaborating on three important implications of the thesis: (1) as new potentially influential factors about the phenomenon of interest are identified, findings from past research that had not accounted for those factors might prove to be insufficient or be put into question; (2) there are increased methodological challenges for researchers as they seek to design new studies that pay due regard to research advances about all relevant and potentially influential factors surrounding the phenomenon of interest; and (3) as a wider range of potentially influential factors get discovered and considered about a particular phenomenon, research knowledge becomes not only more refined, and presumably more accurate, but possibly more fragmented too.
Hypothalamic–pituitary–adrenal axis suppression by inhaled or nasal corticosteroids in HIV-infected patients
Authors: Besemer Femke , Kramers Cornelis , Brinkman Kees , Hermus Ad R. M. M. , van Herwaarden Antonius E. , Burger David M.
Published: March 2020

Background Inhaled or nasal corticosteroids can cause suppression of the hypothalamic–pituitary–adrenal (HPA) axis. Early detection is important because this suppression can be associated with significant morbidity. Objective To explore the adverse effect of hypothalamic–pituitary–adrenal suppression by local corticosteroids in HIV-infected patients. Method Ambulatory HIV-infected patients were selected if they used both antiretroviral treatment and inhaled or nasal corticosteroid. Suppression of hypothalamic–pituitary–adrenal axis was defined as a morning plasma cortisol below 80 nmol/L or a cortisol below 550 nmol/L during a 250 mcg adrenocorticotropic hormone-stimulation test. Results Twelve patients were tested; four of them were taking a CYP3A4 inhibitor. All patients had a normal morning plasma cortisol. Suppression of the hypothalamic–pituitary–adrenal axis during the ACTH stimulation test was identified in three of the twelve patients. None of these three individuals were taking a CYP3A4 inhibitor. Conclusion Hypothalamic–pituitary–adrenal axis suppression is frequently identified in patients on inhaled or nasal corticosteroids. CYP3A4 inhibitors such as ritonavir or cobicistat may increase the chance of this adverse effect. In this study we did not identify HPA axis suppression in patients taking CYP3A4 inhibitors. This may be related to the fact that 2 of these 4 patients used beclomethasone, a corticosteroid not metabolized by CYP3A4.

ClinicalTrials.gov Identifier NCT02501486.
Correction to: Examining acculturation orientations and perceived cultural distance among immigrant adolescents in Portugal: links to performance in reading, mathematics, and science
Authors: Melkonian Michael , Areepattamannil Shaljan , Menano Luisa , Fidalgo Patricia
Published: March 2020

The article “Examining acculturation orientations and perceived cultural distance among immigrant adolescents in Portugal: links to performance in reading, mathematics, and science”, written by Michael Melkonian, Shaljan Areepattamannil, Luisa Menano, Patricia Fidalgo, was originally published Online First without Open Access. After publication in volume 22, issue 4, page 969–989 the author decided to opt for Open Choice and to make the article an Open Access publication.
Developing a Smart Home Solution Based on Personalized Intelligent Interior Units to Promote Activity and Customized Healthcare for Aging Society
Authors: Hu Rongbo , Linner Thomas , Trummer Julian , Güttler Jörg , Kabouteh Amir , Langosch Katharina , Bock Thomas
Published: March 2020

The world’s population is aging at an unprecedented pace. Aging society is not only a severe crisis in the developed world, but also a rigorous challenge in emerging economies. Many age-related diseases are fostered by the lack of physical, cognitive, and social activities. Increasing the activity level has many benefits for the elderly and can improve their independence. Based on the analysis of the state-of-the-art and shortcomings of the current smart home solutions, the EU-funded research project REACH aims to develop a service system that will turn clinical and care environments into personalized modular sensing, prevention, and intervention systems that encourage the elderly to become healthy through various activities. To achieve that goal, the research team developed a series of smart furniture (PI2Us) that materialize the research concepts and functionality seamlessly into the various environments. Specifically, the development process and the functionality testing results of the PI2Us are reported in detail. In addition, a simulated smart home solution concept (TRACK) integrating key assistive technologies developed is proposed to create a comprehensive interior living and care environment for elderly users. Due to its modularity and flexibility, the partial or entire solution can be easily adapted and rapidly deployed in different use case settings in Europe, which allows the project consortium to execute different testing activities. In the next phase, the research team will focus on enhancing the usability and performance of the prototypes in order to eventually push them to the market. In conclusion, this research provides an innovative smart home solution for the industry to mitigate the impact of aging society.
Tight gas production model considering TPG as a function of pore pressure, permeability and water saturation
Authors: Zafar Atif , Su Yu-Liang , Li Lei , Fu Jin-Gang , Mehmood Asif , Ouyang Wei-Ping , Zhang Mian
Published: March 2020

Threshold pressure gradient has great importance in efficient tight gas field development as well as for research and laboratory experiments. This experimental study is carried out to investigate the threshold pressure gradient in detail. Experiments are carried out with and without back pressure so that the effect of pore pressure on threshold pressure gradient may be observed. The trend of increasing or decreasing the threshold pressure gradient is totally opposite in the cases of considering and not considering the pore pressure. The results demonstrate that the pore pressure of tight gas reservoirs has great influence on threshold pressure gradient. The effects of other parameters like permeability and water saturation, in the presence of pore pressure, on threshold pressure gradient are also examined which show that the threshold pressure gradient increases with either a decrease in permeability or an increase in water saturation. Two new correlations of threshold pressure gradient on the basis of pore pressure and permeability, and pore pressure and water saturation, are also introduced. Based on these equations, new models for tight gas production are proposed. The gas slip correction factor is also considered during derivation of this proposed tight gas production models. Inflow performance relationship curves based on these proposed models show that production rates and absolute open flow potential are always be overestimated while ignoring the threshold pressure gradients.
Fertility History and Biomarkers Using Prospective Data: Evidence From the 1958 National Child Development Study
Authors: Sironi Maria , Ploubidis George B. , Grundy Emily M.
Published: March 2020

Research on the later-life health implications of fertility history has predominantly considered associations with mortality or self-reported indicators of health. Most of this previous research has either not been able to account for selection factors related to both early-life and later-life health or has had to rely on retrospectively reported accounts of childhood circumstances. Using the 1958 National Child Development Study, and in particular the biomedical survey conducted in 2002–2003, we investigate associations between fertility histories (number of children and age at first and at last birth) and biomarkers for cardiometabolic risk and respiratory function in midlife among both men and women. Results from models that adjusted for a very wide range of childhood factors, including early-life socioeconomic position, cognitive ability, and mental health, showed weak associations between parity and biomarkers. However, we found an inverse association between age at first birth and biomarkers indicative of worse cardiometabolic health, with poorer outcomes for those with very young ages at entry to parenthood and increasingly better outcomes for those becoming parents at older ages. A very young age at last birth was also associated with less favorable biomarker levels, especially among women. Results highlight the value of prospectively collected data and the availability of biomarkers in studies of life course determinants of health in midlife and later.
Hybrid projective combination–combination synchronization in non-identical hyperchaotic systems using adaptive control
Authors: Khan Ayub , Chaudhary Harindri
Published: March 2020

In this paper, we investigate a hybrid projective combination–combination synchronization scheme among four non-identical hyperchaotic systems via adaptive control method. Based on Lyapunov stability theory, the considered approach identifies the unknown parameters and determines the asymptotic stability globally. It is observed that various synchronization techniques, for instance, chaos control problem, combination synchronization, projective synchronization, etc. turn into particular cases of combination–combination synchronization. The proposed scheme is applicable to secure communication and information processing. Finally, numerical simulations are performed to demonstrate the effectivity and correctness of the considered technique by using MATLAB.
A Genealogy of the Anthropocene: The End of Risk and Limits
Authors: Charbonnier Pierre
Published: March 2020

This article aims to shed light on the emergence of the Anthropocene as a concept within the social sciences and philosophy. It frames this evolution in the wider context of a crisis of knowledge, confronted with the need to consider global climate change as both an empirical ground and an inescapable political horizon. The central hypothesis is that the organization of knowledge concerning the relationships between modernity and nature has undergone a profound shift over the last decade, necessitating a reconfiguration of the two main concepts on which this knowledge relied: risk and limits. To consider the present situation through the concept of the Anthropocene is to imply that the rationality of risk (i.e., the suspension of modern political autonomy) and the notion of a fundamental limit to material development can no longer be considered separately. In the final part of the article, this hypothesis makes it possible to discuss some aspects of our current epistemological configuration.