bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristic retinal atrophy pattern allows differentiation between pediatric MOGAD and MS after a single optic neuritis episode
Authors: Pakeerathan T. , Havla J. , Schwake C. , Salmen A. , Bigi S. , Abegg M. , Brügger D. , Ferrazzini T. , Runge A.-K. , Breu M. , Kornek B. , Bsteh G. , Felipe-Rucián A. , Ringelstein M. , Aktas O. , Karenfort M. , Wendel E. , Kleiter I. , Hellwig K. , Kümpfel T. , Thiels C. , Lücke T. , Gold R. , Rostasy K. , Ayzenberg I.
Published: July 2022

Background

Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MSped) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGADped) in children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode.

Methods

Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls.

Results

Thirteen MOGADped (10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MSped (14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGADped compared to MSped (pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm, p < 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm3, p < 0.001). Neither other macular layers nor P100 latency differed. MOGADped developed global atrophy affecting all peripapillary segments, while MSped displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGADped). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%, p = 0.016).

Conclusion

First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.
Long-term safety, discontinuation and mortality in an Italian cohort with advanced Parkinson’s disease on levodopa/carbidopa intestinal gel infusion
Authors: Garrì Federica , Russo Francesco Paolo , Carrer Tommaso , Weis Luca , Pistonesi Francesca , Mainardi Michele , Sandre Michele , Savarino Edoardo , Farinati Fabio , Del Sorbo Francesca , Soliveri Paola , Calandrella Daniela , Biundo Roberta , Carecchio Miryam , Zecchinelli Anna Lena , Pezzoli Gianni , Antonini Angelo
Published: July 2022

Introduction

Levodopa/carbidopa intestinal gel (LCIG) is an effective treatment in patients with advanced Parkinson’s disease (PD) with consolidated evidence of clinical efficacy. However, only few studies have assessed long-term safety, causes of discontinuation, mortality, and relative predictors.

Methods

We conducted a retrospective analysis of 79 PD patients treated with LCIG between 2005 and 2020 in two Italian Neurological Centers, recording all adverse events (AEs), including weight loss (WL). Kaplan–Meier curve was used to estimate the time to discontinuation and survival. Cox proportional hazard model was employed to identify predictors of discontinuation and mortality, while Pearson’s correlation was used to analyze predictors of WL.

Results

The average follow-up was 47.7 ± 40.5 months and the median survival from disease onset was 25 years. There were three cases of polyradiculoneuropathy Guillain–Barre syndrome-like, all occurred in the early years of LCIG treatment. Twenty-five patients died (32%), 18 on LCIG (including one suicide) and seven after discontinuation. The mean WL was 3.62 ± 7.5 kg, which correlated with levodopa dose at baseline (p = 0.002), levodopa equivalent daily dose (LEDD) baseline (p = 0.017) and off-duration (p = 0.0014), but not dyskinesia. Peristomal complications emerged as a negative predictor of discontinuation (p = 0.008).

Conclusions

LCIG has a relatively satisfactory long-term safety profile and efficacy and a relatively low rate of discontinuation. Peristomal complications may represent a predictor of longer duration of therapy. According to the mortality analysis, LCIG patients show a long lifespan. Delaying the initiation of LCIG does not affect the sustainability of LCIG therapy.
Health and related behaviours of fly-in fly-out workers in the mining industry in Australia: a cross-sectional study
Authors: Asare Bernard Yeboah-Asiamah , Robinson Suzanne , Powell Daniel , Kwasnicka Dominika
Published: July 2022

Background

Fly-In Fly-Out (FIFO), which entails travelling mostly from the urban areas to stay and work in remote areas for designated periods and travel back home to spend designated days of leave, has become a common work arrangement in the mining sector globally. This study examined the mental and physical health of FIFO workers and described their health-related behaviours during on-and off-shift periods.

Methods

A cross-sectional study was conducted with FIFO workers (N = 216) in the mining industry in Australia who completed an online survey. Paired t-test and McNemer’s analysis examined the differences in health-related behaviours during workers’ on-and off-shift days. Logistic regression examined the predictors of physical health and psychological distress status of FIFO workers.

Results

Workers reported longer sleep duration (7.5 ± 1.5 h vs 6.3 ± 1.2 h, p < 0.001) and better sleep quality (78.2% vs 46.3%, p < 0.001) during off-shift nights than on on-shift nights. Smoking prevalence was 26.4%, and workers reported smoking a similar number of cigarettes per day during on-and off-shift days. Most workers reported drinking alcohol (86.1%) and more often at risky levels during off-shift than on-shift days (57.9% vs 34.3%, p < 0.001). Fruits and vegetable consumption was low but with higher vegetable intake during off-shift days (2.8 ± 1.4 vs 2.3 ± 1.3 serves, p < 0.001). Workers had good physical health status (91.2%), but 71.4% were overweight/obese and 33.4% indicated high levels of psychological distress. Working on long shifts (OR 6.63, 95% CI 1.84–23.91) and smoking (OR 7.17, 95% CI 2.67–19.26) were linked to high psychological distress.

Conclusions

The prevalence of psychological distress and risky health behaviours was high. Interventions should aim to reduce psychological distress and support multiple behaviour changes, considering FIFO work-related characteristics including long shift hours.
Quenched universality for deformed Wigner matrices
Authors: Cipolloni Giorgio , Erdős László , Schröder Dominik
Published: July 2022

Following E. Wigner’s original vision, we prove that sampling the eigenvalue gaps within the bulk spectrum of a fixed (deformed) Wigner matrix H yields the celebrated Wigner-Dyson-Mehta universal statistics with high probability. Similarly, we prove universality for a monoparametric family of deformed Wigner matrices $$H+xA$$

H
+
x
A

with a deterministic Hermitian matrix A and a fixed Wigner matrix H, just using the randomness of a single scalar real random variable x. Both results constitute quenched versions of bulk universality that has so far only been proven in annealed sense with respect to the probability space of the matrix ensemble.
Component Order Connectivity in Directed Graphs
Authors: Bang-Jensen Jørgen , Eiben Eduard , Gutin Gregory , Wahlström Magnus , Yeo Anders
Published: July 2022

A directed graph D is semicomplete if for every pair x, y of vertices of D,  there is at least one arc between x and y. Thus, a tournament is a semicomplete digraph. In the Directed Component Order Connectivity (DCOC) problem, given a digraph $$D=(V,A)$$

D
=
(
V
,
A
)

and a pair of natural numbers k and $$\ell $$
ℓ
, we are to decide whether there is a subset X of V of size k such that the largest strongly connected component in $$D-X$$

D
-
X

has at most $$\ell $$
ℓ
vertices. Note that DCOC reduces to the Directed Feedback Vertex Set problem for $$\ell =1.$$

ℓ
=
1
.

We study the parameterized complexity of DCOC for general and semicomplete digraphs with the following parameters: $$k, \ell ,\ell +k$$

k
,
ℓ
,
ℓ
+
k

and $$n-\ell $$

n
-
ℓ

. In particular, we prove that DCOC with parameter k on semicomplete digraphs can be solved in time $$O^*(2^{16k})$$

O
∗

(

2

16
k

)

but not in time $$O^*(2^{o(k)})$$

O
∗

(

2

o
(
k
)

)

unless the Exponential Time Hypothesis (ETH) fails. The upper bound $$O^*(2^{16k})$$

O
∗

(

2

16
k

)

implies the upper bound $$O^*(2^{16(n-\ell )})$$

O
∗

(

2

16
(
n
-
ℓ
)

)

for the parameter $$n-\ell .$$

n
-
ℓ
.

We complement the latter by showing that there is no algorithm of time complexity $$O^*(2^{o({n-\ell })})$$

O
∗

(

2

o
(

n
-
ℓ

)

)

unless ETH fails. Finally, we improve (in dependency on $$\ell $$
ℓ
) the upper bound of Göke, Marx and Mnich (2019) for the time complexity of DCOC with parameter $$\ell +k$$

ℓ
+
k

on general digraphs from $$O^*(2^{O(k\ell \log (k\ell ))})$$

O
∗

(

2

O
(
k
ℓ
log
(
k
ℓ
)
)

)

to $$O^*(2^{O(k\log (k\ell ))}).$$

O
∗

(

2

O
(
k
log
(
k
ℓ
)
)

)

.

Note that Drange, Dregi and van ’t Hof (2016) proved that even for the undirected version of DCOC on split graphs there is no algorithm of running time $$O^*(2^{o(k\log \ell )})$$

O
∗

(

2

o
(
k
log
ℓ
)

)

unless ETH fails and it is a long-standing problem to decide whether Directed Feedback Vertex Set admits an algorithm of time complexity $$O^*(2^{o(k\log k)}).$$

O
∗

(

2

o
(
k
log
k
)

)

.
Exploring the perceived impact of social support on the health behaviours of people living with and beyond cancer during the COVID-19 pandemic: a qualitative study
Authors: Miller Natalie , Conway Rana , Pini Simon , Buck Caroline , Gil Natalie , Lally Phillippa , Beeken Rebecca J. , Fisher Abigail
Published: July 2022

Purpose

Social support facilitated healthy behaviours in people living with and beyond cancer (LWBC) before the COVID-19 pandemic. Little is known about how social support impacted their health behaviours during the pandemic when social restrictions were imposed. The aim of this study was to qualitatively explore how social support was perceived to impact the health behaviours of people LWBC during the COVID-19 pandemic.

Methods

Semi-structured interviews were conducted via telephone with 24 adults living with and beyond breast, prostate and colorectal cancer. Inductive and deductive framework analysis was used to analyse the data.

Results

Five themes developed. These were (1) Companionship and accountability as motivators for physical activity, (2) Social influences on alcohol consumption, (3) Instrumental support in food practices, (4) Informational support as important for behaviour change and (5) Validation of health behaviours from immediate social networks.

Conclusion

This study described how companionship, social influence, instrumental support, informational support and validation were perceived to impact the health behaviours of people LWBC during the COVID-19 pandemic. Interventions for people LWBC could recommend co-participation in exercise with friends and family; promote the formation of collaborative implementation intentions with family to reduce alcohol consumption; and encourage supportive communication between partners about health behaviours. These interventions would be useful during pandemics and at other times. Government policies to help support clinically extremely vulnerable groups of people LWBC during pandemics should focus on providing access to healthier foods.
Automatic reconstruction of irregular shape defects in pulsed thermography using deep learning neural network
Authors: Liu Haochen , Li Wenhan , Yang Lichao , Deng Kailun , Zhao Yifan
Published: July 2022

Quantitative defect and damage reconstruction play a critical role in industrial quality management. Accurate defect characterisation in Infrared Thermography (IRT), as one of the widely used Non-Destructive Testing (NDT) techniques, always demands adequate pre-knowledge which poses a challenge to automatic decision-making in maintenance. This paper presents an automatic and accurate defect profile reconstruction method, taking advantage of deep learning Neural Networks (NN). Initially, a fast Finite Element Modelling (FEM) simulation of IRT is introduced for defective specimen simulation. Mask Region-based Convolution NN (Mask-RCNN) is proposed to detect and segment the defect using a single thermal frame. A dataset with a single-type-shape defect is tested to validate the feasibility. Then, a dataset with three mixed shapes of defect is inspected to evaluate the method’s capability on the defect profile reconstruction, where an accuracy over 90% on Intersection over Union (IoU) is achieved. The results are compared with several state-of-the-art of post-processing methods in IRT to demonstrate the superiority at detailed defect corners and edges. This research lays solid evidence that AI deep learning algorithms can be utilised to provide accurate defect profile reconstruction in thermography NDT, which will contribute to the research community in material degradation analysis and structural health monitoring.
Meta-analytical analysis on components released from resin-based dental materials
Authors: De Angelis Francesco , Sarteur Nela , Buonvivere Matteo , Vadini Mirco , Šteffl Michal , D’Arcangelo Camillo
Published: July 2022

Objectives

Resin-based materials are applied in every branch of dentistry. Due to their tendency to release substances in the oral environment, doubts have been raised about their actual safety. This review aims to provide a comprehensive analysis of the last decade literature regarding the concentrations of elutable substances released from dental resin-based materials in different type of solvents.

Materials and methods

All the literature published on dental journals between January 2010 and April 2022 was searched using international databases (PubMed, Scopus, Web of Science). Due to strict inclusion criteria, only 23 papers out of 877 were considered eligible. The concentration of eluted substances related to surface and volume of the sample was analyzed, considering data at 24 h as a reference. The total cumulative release was examined as well.

Results

The most eluted substances were HEMA, TEGDMA, and BPA, while the less eluted were Bis-GMA and UDMA. Organic solvents caused significantly higher release of substances than water-based ones. A statistically significant inverse correlation between the release of molecules and their molecular mass was observed. A statistically significant positive correlation between the amount of released molecule and the specimen surface area was detected, as well as a weak positive correlation between the release and the specimen volume.

Conclusions

Type of solvent, molecular mass of eluates, and specimen surface and volume affect substances release from materials.

Clinical relevance

It could be advisable to rely on materials based on monomers with a reduced elution tendency for clinical procedures.
Anti-vinculin antibodies as a novel biomarker in Egyptian patients with systemic sclerosis
Authors: Ibrahim Noha Hosni , Fawzy Iman Mahmoud , Gouda Tahany Mahmoud , El Sayed Rasha Abdel Hameed , Morsi Maha Hosni , Sabry Al Shimaa Mohamed , Hashaad Nashwa Ismail
Published: July 2022

Introduction

Systemic sclerosis (SSc) is an autoimmune disorder that causes vasculopathy and scarring, most commonly in the lungs and skin, but it can also affect other organs. Endothelial vinculin plays a critical role in angiogenesis regulation. Therefore, vinculin overexpression in SSc may give rise to anti-vinculin antibodies, which may contribute to the development of SSc vasculopathy. The current research aims to (1) determine whether anti-vinculin autoantibodies play a significant role in the diagnosis of SSc and (2) compare anti-vinculin serum levels between two scleroderma patient populations, namely, pulmonary artery hypertension (PAH)–predominant and interstitial pulmonary fibrosis (IPF)–predominant groups.

Methods

This research included 140 participants categorized into three groups: group I—patients with PAH-predominant; group II—patients with ILD-predominant; group III—the control group. Anti-vinculin antibodies were detected in serum samples collected from all participants using ELISA. All subjects underwent high-resolution computed tomography (CT), diffusing capacity for carbon monoxide, and pulmonary function tests.

Results

Patients in group I (PAH-predominant group, N = 35) were 41.3 [± 11.4] years old, with 80% being women. Patients in group II (ILD-predominant group, N = 35) were 41.0 [± 11.5] years old. The SSc group showed significantly higher anti-vinculin antibody levels than the control group (P < 0.001). The PAH-predominant group demonstrated significantly higher anti-vinculin antibody levels and anti-vinculin positivity than the ILD-predominant group.

Conclusion

Anti-vinculin antibodies in the blood appear to be diagnostic biomarkers for scleroderma. Furthermore, they shed light on some novel perspectives on the pathophysiology of specific lung fibrotic changes.

Key Points• This study included two groups of systemic sclerosis patients (PAH-predominant group, ILD-predominant group) as well as a control group to investigate the significance of anti-vinculin antibodies in such cases.• Our results have demonstrated that anti-vinculin antibodies can play a significant role in diagnosing and monitoring systemic sclerosis disease.
Die deutsche Abhängigkeit von russischem Gas
Authors: Gleißner Werner , Follert Florian
Published: July 2022

Risikomanagement erscheint zunächst als originär betriebswirtschaftliches Sujet. Globale Krisen wie die internationale Finanzkrise, die COVID-19-Pandemie oder der russische Angriffskrieg sowie die daraus folgenden energiepolitischen Fragen zeigen jedoch, dass der staatliche Umgang mit Risiken eine systematische Integration in den politischen Entscheidungsprozess benötigt. Es ist essenziell, Entscheidungstragende für staatliches Risikomanagement zu sensibilisieren und Instrumente sowie Institutionen aufzuzeigen, die in der Lage sein könnten, die gegenwärtige Risikoblindheit zu mindern, um Deutschland aus der Perspektive des Risikomanagements zu einem „robusten Staat“ weiterzuentwickeln.
Chronischer Investitionsmangel — eine deutsche Krankheit
Authors: Rösel Felix , Wolffson Julia
Published: July 2022

Kein EU-Land investiert so wenig in seine öffentliche Infrastruktur wie Deutschland. Im europäischen Durchschnitt wurden seit 2000 jährlich etwa 3,7% des BIP für Straßen, Schulbau und andere staatliche Investitionen aufgewendet. Deutschland lag mit durchschnittlich 2,1% deutlich darunter. Diese Lücke lässt sich in Regressionsanalysen weder durch ökonomische, fiskalische, demografische noch institutionelle Faktoren erklären, auch nicht durch die Schuldenbremse. Die deutsche Investitionsschwäche scheint zu einer chronischen Krankheit geworden zu sein, für die andere Faktoren wie langwierige Planungsverfahren und Personalnot verantwortlich sein dürften. Für eine Kurskorrektur könnte es allerdings angesichts der sich zuspitzenden Fachkräfte- und Materialknappheit möglicherweise zu spät sein.
Homeoffice spart ein Zehntel Treibstoff ein
Authors: Jost Oskar , Seibert Holger
Published: July 2022

Aufgrund der rapide gestiegenen Treibstoffpreise wird die Debatte zu möglichen Einsparpotenzialen bei Treibstoff wichtiger. So könnten die in der Coronapandemie entwickelten Homeofficepotenziale dazu genutzt werden, um Pendelaufkommen zu reduzieren und so den Treibstoffverbrauch zu verringern. Um Einsparpotenziale zu bestimmen, wird eine für den deutschen Raum vorliegende Untersuchung genutzt, die Homeofficepotenziale für einzelne Berufsfelder ausweist. Diese Potenziale werden mit der Beschäftigungsstatistik der Bundesagentur für Arbeit kombiniert. Diese Statistik liefert erste berufsspezifische Informationen zu Pendeldistanzen der Beschäftigten, die über Gemeindegrenzen hinweg pendeln und so besonders von hohen Treibstoffpreisen betroffen sind.
Potenziale entwickeln und Wissen teilen: deutsche Unternehmen in Afrika
Authors: Dohse Dirk , Fehrenbacher Sophia , von Carlowitz Philipp
Published: July 2022

Afrika ist ein Kontinent der Chancen, der in der künftigen weltwirtschaftlichen Arbeitsteilung eine deutlich größere Rolle spielen dürfte als bisher. Dennoch tut sich die deutsche Wirtschaft bislang schwer. Die digitale Transformation verändert die Investitions- und Innovationsbedingungen in Afrika. Daraus ergeben sich auch für deutsche Unternehmen Chancen auf dem afrikanischen Kontinent. Die Politik sollte Rahmenbedingungen für ein stärkeres privatwirtschaftliches Engagement deutscher und europäischer Unternehmen in Afrika schaffen.
Mehr Selbstdisziplin macht Politikberatung besser
Authors: Wagner Gert G.
Published: July 2022

There is a differentiated literature on policy advice, but it is largely disconnected from the literature (and the underlying research landscape) on academic communication, which originally dealt only with the natural sciences. And both strands of the discussion are barely connected to the figure of the „public intellectual“ who has played an important role in the humanities and social sciences for decades. This is a role that, as discussed in this article, is now played digitally by many scholars with low barriers to entry. This creates new problems, which can be addressed by research ethics. Of course, the relevant literature in communication studies is not discussed in detail in this article, but it is pointed out that (selective) examination of this literature might also be worthwhile with regard to policy advice.
Datenmangel und andere Probleme der wirtschaftswissenschaftlichen Politikberatung in Deutschland
Authors: Haucap Justus
Published: July 2022

The relationship between politics and scientific policy advice is still characterized by misunderstandings on both sides. A major point of criticism from the political arena is repeatedly the lacking concern for reality in economics. This problem, however, is at least partly homemade, as the data situation is not good in many areas in Germany, even for research purposes. In addition to other reasons — such as incentives to publish in top international journals, which in turn seems to be easier with U.S. topics or data than with issues relevant to other countries — the lack of data availability also contributes to the fact that economists in the D/A/CH area deal less with “local” topics than would be possible.
Metyltetraprole activity against plant pathogens with relatively rare cytochrome b haplotypes for azoxystrobin resistance
Authors: Matsuzaki Yuichi , Uda Yukie , Harada Toshiyuki , Iwahashi Fukumatsu
Published: July 2022

Metyltetraprole is a novel quinone outside inhibitor (QoI) fungicide designed to avoid cross-resistance in cytochrome b G143A-harboring QoI-resistant phytopathogenic fungi. The resistance factors of G143A-harboring fungal isolates for metyltetraprole are around 1, but > 200 for the reference QoI fungicide azoxystrobin. In this study of metyltetraprole activities against azoxystrobin-resistant isolates carrying G137R, G137S, L299F, N256S + L299F, or L275F + L299F in cytochrome b, metyltetraprole had potent activity against all isolates with these cytochrome b haplotypes. The resistance factors ranged from 0.7 to 2.9 for metyltetraprole and from 3.0 to 175.1 for azoxystrobin. We revealed unique metyltetraprole inhibitory activities against QoI-resistant plant pathogens.
Dictionary learning compressed sensing reconstruction: pilot validation of accelerated echo planar J-resolved spectroscopic imaging in prostate cancer
Authors: Joy Ajin , Nagarajan Rajakumar , Saucedo Andres , Iqbal Zohaib , Sarma Manoj K. , Wilson Neil , Felker Ely , Reiter Robert E. , Raman Steven S. , Thomas M. Albert
Published: July 2022

Objectives

This study aimed at developing dictionary learning (DL) based compressed sensing (CS) reconstruction for randomly undersampled five-dimensional (5D) MR Spectroscopic Imaging (3D spatial + 2D spectral) data acquired in prostate cancer patients and healthy controls, and test its feasibility at 8x and 12x undersampling factors.

Materials and methods

Prospectively undersampled 5D echo-planar J-resolved spectroscopic imaging (EP-JRESI) data were acquired in nine prostate cancer (PCa) patients and three healthy males. The 5D EP-JRESI data were reconstructed using DL and compared with gradient sparsity-based Total Variation (TV) and Perona-Malik (PM) methods. A hybrid reconstruction technique, Dictionary Learning-Total Variation (DLTV), was also designed to further improve the quality of reconstructed spectra.

Results

The CS reconstruction of prospectively undersampled (8x and 12x) 5D EP-JRESI data acquired in prostate cancer and healthy subjects were performed using DL, DLTV, TV and PM. It is evident that the hybrid DLTV method can unambiguously resolve 2D J-resolved peaks including myo-inositol, citrate, creatine, spermine and choline.

Conclusion

Improved reconstruction of the accelerated 5D EP-JRESI data was observed using the hybrid DLTV. Accelerated acquisition of in vivo 5D data with as low as 8.33% samples (12x) corresponds to a total scan time of 14 min as opposed to a fully sampled scan that needs a total duration of 2.4 h (TR = 1.2 s, 32 $${k}_{x}$$

k
x

×16 $${k}_{y}$$

k
y

×8 $${k}_{z}$$

k
z

, 512 $${t}_{2}$$

t
2

and 64 $${t}_{1}$$

t
1

).
Fluorescent hiPSC-derived MYH6-mScarlet cardiomyocytes for real-time tracking, imaging, and cardiotoxicity assays
Authors: Maria Cherian Reeja , Prajapati Chandra , Penttinen Kirsi , Häkli Martta , Koivisto Janne T. , Pekkanen-Mattila Mari , Aalto-Setälä Katriina
Published: July 2022

Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) hold great potential in the cardiovascular field for human disease modeling, drug development, and regenerative medicine. However, multiple hurdles still exist for the effective utilization of hiPSC-CMs as a human-based experimental platform that can be an alternative to the current animal models. To further expand their potential as a research tool and bridge the translational gap, we have generated a cardiac-specific hiPSC reporter line that differentiates into fluorescent CMs using CRISPR-Cas9 genome editing technology. The CMs illuminated with the mScarlet fluorescence enable their non-invasive continuous tracking and functional cellular phenotyping, offering a real-time 2D/3D imaging platform. Utilizing the reporter CMs, we developed an imaging-based cardiotoxicity screening system that can monitor distinct drug-induced structural toxicity and CM viability in real time. The reporter fluorescence enabled visualization of sarcomeric disarray and displayed a drug dose–dependent decrease in its fluorescence. The study also has demonstrated the reporter CMs as a biomaterial cytocompatibility analysis tool that can monitor dynamic cell behavior and maturity of hiPSC-CMs cultured in various biomaterial scaffolds. This versatile cardiac imaging tool that enables real time tracking and high-resolution imaging of CMs has significant potential in disease modeling, drug screening, and toxicology testing.

Graphical abstract
Interleukin-6 Downregulates the Expression of Vascular Endothelial-Cadherin and Increases Permeability in Renal Glomerular Endothelial Cells via the Trans-Signaling Pathway
Authors: Yang Yong-Chang , Fu Hui , Zhang Bo , Wu Yu-Bin
Published: July 2022

The pathogenesis of IgA nephropathy (IgAN) is still unknown, but reportedly, interleukin 6 (IL-6) is involved in this process. However, its role in damaging glomerular endothelial cells is still unclear. Therefore, in this study, to clarify the mechanism of the pathogenesis of IgAN, we investigated the effect of IL-6 on the permeability of glomerular endothelial cells. A rat model of IgAN was established, and the animals divided into two groups, namely, the normal and IgAN groups. Glomerular endothelial cell injury was evaluated via electron microscopy. Furthermore, IL-6-induced changes in the permeability of human renal glomerular endothelial cells (HRGECs) were measured via trans-endothelial resistance (TEER) measurements and fluorescein isothiocyanate-dextran fluorescence. Furthermore, vascular endothelial-cadherin (VE-cadherin) was overexpressed to clarify the effect of IL-6 on HRGEC permeability, and to determine the pathway by which it acts. The classical signaling pathway was blocked by silencing IL-6R and the trans-signaling pathway was blocked by sgp30Fc. In IgAN rats, electron microscopy showed glomerular endothelial cell damage and western blotting revealed a significant increase in IL-6 expression, while VE-cadherin expression decreased significantly in the renal tissues. IL-6/IL-6R stimulation also significantly increased the permeability of HRGECs (p < 0.05). This effect was significantly reduced by VE-cadherin overexpression (p < 0.01). After IL-6R was silenced, IL-6/IL-6R still significantly reduced VE-cadherin expression and sgp30Fc blocked the trans-signaling pathway as well as the upregulation of IL-6/IL-6R-induced VE-cadherin expression. This suggests that IL-6 mainly acts via the trans-signaling pathway. IL-6 increased the permeability of HRGECs by decreasing the expression of VE-cadherin via the trans-signaling pathway.
Stencil Calculations with Algorithmic Skeletons for Heterogeneous Computing Environments
Authors: Herrmann Nina , de Melo Menezes Breno A. , Kuchen Herbert
Published: July 2022

The development of parallel applications is a difficult and error-prone task, especially for inexperienced programmers. Stencil operations are exceptionally complex for parallelization as synchronization and communication between the individual processes and threads are necessary. It gets even more difficult to efficiently distribute the computations and efficiently implement communication when heterogeneous computing environments are used. For using multiple nodes, each having multiple cores and accelerators such as GPUs, skills in combining frameworks such as MPI, OpenMP, and CUDA are required. The complexity of parallelizing the stencil operation increases the need for abstracting from the platform-specific details and simplify parallel programming. One way to abstract from details of parallel programming is to use algorithmic skeletons. This work introduces an implementation of the MapStencil skeleton that is able to generate parallel code for distributed memory environments, using multiple nodes with multicore CPUs and GPUs. Examples of practical applications of the MapStencil skeleton are the Jacobi Solver or the Canny Edge Detector. The main contribution of this paper is a discussion of the difficulties when implementing a universal Skeleton for MapStencil for heterogeneous computing environments and an outline of the identified best practices for communication intense skeletons.
Novel RAB27A Variant Associated with Late-Onset Hemophagocytic Lymphohistiocytosis Alters Effector Protein Binding
Authors: Zondag Timo C. E. , Torralba-Raga Lamberto , Van Laar Jan A. M. , Hermans Maud A. W. , Bouman Arjen , Hollink Iris H. I. M. , Van Hagen P. Martin , Briggs Deborah A. , Hume Alistair N. , Bryceson Yenan T.
Published: July 2022

Autosomal recessive mutations in RAB27A are associated with Griscelli syndrome type 2 (GS2), characterized by hypopigmentation and development of early-onset, potentially fatal hemophagocytic lymphohistiocytosis (HLH). We describe a 35-year old male who presented with recurrent fever, was diagnosed with Epstein-Barr virus-driven chronic lymphoproliferation, fulfilled clinical HLH criteria, and who carried a novel homozygous RAB27A c.551G > A p.(R184Q) variant. We aimed to evaluate the contribution of the identified RAB27A variant in regard to the clinical phenotype as well as cellular and biochemical function. The patient displayed normal pigmentation as well as RAB27A expression in blood-derived cells. However, patient NK and CD8+ T cell exocytosis was low. Ectopic expression of the RAB27A p.R184Q variant rescued melanosome distribution in mouse Rab27a-deficient melanocytes, but failed to increase exocytosis upon reconstitution of human RAB27A-deficient CD8+ T cells. Mechanistically, the RAB27A p.R184Q variant displayed reduced binding to SLP2A but augmented binding to MUNC13-4, two key effector proteins in immune cells. MUNC13-4 binding was particularly strong to an inactive RAB27A p.T23N/p.R184Q double mutant. RAB27A p.R184Q was expressed and could facilitate melanosome trafficking, but did not support lymphocyte exocytosis. The HLH-associated RAB27A variant increased Munc13-4 binding, potentially representing a novel mode of impairing RAB27A function selectively in hematopoietic cells.
Modernizing quantum annealing II: genetic algorithms with the inference primitive formalism
Authors: Chancellor Nicholas
Published: July 2022

Quantum annealing, a method of computing where optimization and machine learning problems are mapped to physically implemented energy landscapes subject to quantum fluctuations, allows for these fluctuations to be used to assist in finding the solution to some of the world’s most challenging computational problems. Recently, this field has attracted much interest because of the construction of large-scale flux-qubit based quantum annealing devices. These devices have since implemented a technique known as reverse annealing which allows the solution space to be searched locally, and algorithms based on these techniques have been tested. In this paper, I develop a formalism for algorithmic design in quantum annealers, which I call the ‘inference primitive’ formalism. This formalism naturally lends itself to expressing algorithms which are structurally similar to genetic algorithms, but where the annealing processor performs a combined crossover/mutation step. I demonstrate how these methods can be used to understand the algorithms which have already been implemented and the compatibility of such controls with a wide variety of other current efforts to improve the performance of quantum annealers.
Does Social and Economic Disadvantage Predict Lower Engagement with Parenting Interventions? An Integrative Analysis Using Individual Participant Data
Authors: Berry Vashti , Melendez-Torres G. J. , Axford Nick , Axberg Ulf , de Castro Bram Orobio , Gardner Frances , Gaspar Maria Filomena , Handegård Bjørn Helge , Hutchings Judy , Menting Ankie , McGilloway Sinéad , Scott Stephen , Leijten Patty
Published: July 2022

There is a social gradient to the determinants of health; low socioeconomic status (SES) has been linked to reduced educational attainment and employment prospects, which in turn affect physical and mental wellbeing. One goal of preventive interventions, such as parenting programs, is to reduce these health inequalities by supporting families with difficulties that are often patterned by SES. Despite these intentions, a recent individual participant data (IPD) meta-analysis of the Incredible Years (IY) parenting program found no evidence for differential benefit by socioeconomic disadvantage (Gardner et al. in Public Health Resesearch 5, 1–144, 2017). However, it did not examine whether this was influenced by engagement in the intervention. Using intervention arm data from this pooled dataset (13 trials; N = 1078), we examined whether there was an SES gradient to intervention attendance (an indicator of engagement). We ran mixed-effects Poisson regression models to estimate incidence rate ratios (IRRs) for program attendance for each of five (binary) markers of SES: low income; unemployment; low education status; teen parent; and lone parent status. The multilevel structure of the data allowed for comparison of within-trial and between-trial effects, including tests for contextual effects. We found evidence that low SES was associated with reduced attendance at parenting programs—an 8–19% reduction depending on the SES marker. However, there was no evidence that this association is impacted by differences in SES composition between trials or by the attendance levels of higher-SES families. The findings underscore the importance of developing and prioritizing strategies that enable engagement in parenting interventions and encourage program attendance by low-SES families.
Establishing thresholds for meaningful within-individual change using longitudinal item response theory
Authors: Bjorner Jakob Bue , Terluin Berend , Trigg Andrew , Hu Jinxiang , Brady Keri J. S. , Griffiths Pip
Published: July 2022

Purpose

Thresholds for meaningful within-individual change (MWIC) are useful for interpreting patient-reported outcome measures (PROM). Transition ratings (TR) have been recommended as anchors to establish MWIC. Traditional statistical methods for analyzing MWIC such as mean change analysis, receiver operating characteristic (ROC) analysis, and predictive modeling ignore problems of floor/ceiling effects and measurement error in the PROM scores and the TR item. We present a novel approach to MWIC estimation for multi-item scales using longitudinal item response theory (LIRT).

Methods

A Graded Response LIRT model for baseline and follow-up PROM data was expanded to include a TR item measuring latent change. The LIRT threshold parameter for the TR established the MWIC threshold on the latent metric, from which the observed PROM score MWIC threshold was estimated. We compared the LIRT approach and traditional methods using an example data set with baseline and three follow-up assessments differing by magnitude of score improvement, variance of score improvement, and baseline-follow-up score correlation.

Results

The LIRT model provided good fit to the data. LIRT estimates of observed PROM MWIC varied between 3 and 4 points score improvement. In contrast, results from traditional methods varied from 2 to 10 points—strongly associated with proportion of self-rated improvement. Best agreement between methods was seen when approximately 50% rated their health as improved.

Conclusion

Results from traditional analyses of anchor-based MWIC are impacted by study conditions. LIRT constitutes a promising and more robust analytic approach to identifying thresholds for MWIC.
Heavy Metal Contamination of the River Nile Environment, Rosetta Branch, Egypt
Authors: Al-Afify Afify D. G. , Abdel-Satar Amaal M.
Published: July 2022

The Rosetta Branch is one of Egypt’s most important Nile River branches, providing freshwater to multiple cities. However, its water quality has been deteriorating, with various wastes containing high loads of heavy metals being discharged into its body of water. Seasonally, water and sediment samples and two native aquatic plants (Ceratophyllum demersum and Eichhornia crassipes) were collected and analyzed from the Rosetta Branch to assess the level of metal contamination (Fe, Mn, Zn, Cu, Pb, Ni, Cd, Cr, and Co) using different metal indices. The levels of some metals in the branch water overstepped those suitable for drinking water and aquatic life. In increasing order, the means of the heavy metal concentrations in branch water (µg/L) were Cd (1.8–4.9) < Co (7.18–28.1) ≈ Ni (9.0–25.1) < Cr (8.56–27.4) < Cu (14–75) < Pb (9.3–67.9) < Zn (22–133) < Mn (68–220) < Fe (396–1640). All the metal indices measured in the sediment confirmed the Ni and Cd contamination, where Ni and Cd in the sediment surpass the sediment quality guidelines in 80% and 53% of samples, respectively, reflecting frequent adverse effects on aquatic organisms. According to the bioconcentration factor, C. demersum and E. crassipes have higher accumulation capacities mainly for Cd than those for other metals considered as major pollutants in the water and sediment of Rosetta Branch, reflecting the role of hydrophytes in the biological treatment of polluted water in aquatic environments.
Consideration of the carbon sequestration potential of seagrass to inform recovery and restoration projects within the Essex Estuaries Special Area of Conservation (SAC), United Kingdom
Authors: Gouldsmith Vanessa , Cooper Andrew
Published: July 2022

A review of available research into the blue carbon potential of seagrass was undertaken. This was then used to inform an analysis of the potential current, historic, and future value of carbon sequestered and stored in the Essex Estuaries Special Area of Conservation (SAC). The assessed status of Zostera in the SAC highlights the extent of historic loss and continued degradation of this designated sub-feature, and current water quality is incompatible with recovery or restoration. Seagrass blue carbon currently stored within the SAC equates to ∼18,350 t C at a sequestration rate of 117.15 t C yr−1, with a lost/potential of 534,700 t C storage capacity. The calculated financial value of current stocks (£4.6 m) is dwarfed by the lost/potential monetary value of carbon storage, £135 m, and the forfeited sequestration of £860,000-worth of carbon annually from degraded habitat. The use of carbon offset credits could help fund the huge potential for restoration that exists within the SAC.
Biomass Production and Nutrient Removal by Perennial Energy Grasses Produced on a Wet Marginal Land
Authors: Cooney Danielle R. , Namoi Nictor , Zumpf Colleen , Lim Soo-Hyun , Villamil Maria , Mitchell Robert , Lee D. K.
Published: July 2022

Growing dedicated bioenergy crops on marginal land can provide beneficial outcomes including biomass production and energy, resource management, and ecosystem services. We investigated the effects of harvest timing (peak standing crop [PEAK] or after killing frost [KF]) and nitrogen (N) fertilizer rates (0, 56, and 112 kg N ha−1) on yield, nutrient concentrations, and nutrient removal rates of perennial grasses on a wet marginal land. We evaluated three monocultures, including switchgrass (Panicum virgatum L., SW), Miscanthus x giganteus (MG), prairie cordgrass (Spartina pectinata Link, PCG), and a polyculture mixture of big bluestem (Andropogon gerardii Vitman), Indiangrass (Sorghastrum nutans (L.) Nash), and sideoats grama (Bouteloua curtipendula Torr., MIX). Increasing the application of N did correlate with increased biomass, concentration, and subsequent removal of nutrients across almost all treatment combinations. In all grass treatments except MG, PEAK harvesting increased yield and nutrient removal. At PEAK harvest, switchgrass is ideal for optimizing both biomass production and nutrient removal. While our results also suggest short-term plasticity for farmers when selecting harvest timing for optimal nutrient removal, KF harvest is recommended to ensure long-term stand longevity and adequate nutrient removal. If the KF harvest is adopted, MG would be the ideal option for optimizing biomass yield potential. Additionally, we found that the yield of polyculture did not vary much with harvest timing, suggesting better yield stability. Future studies should give consideration for long-term evaluation of polyculture mixtures to assess their biomass yields and nutrient removal capacities.
Optimization of integrated production scheduling and vehicle routing problem with batch delivery to multiple customers in supply chain
Authors: Azad Tanzila , Rahman Humyun Fuad , Chakrabortty Ripon K. , Ryan Michael J.
Published: July 2022

In supply chain literature, production coordination and vehicle routing have received a lot of attention. Even though all functions in the supply chain are interrelated, they are normally handled independently. This disconnected approach might lead to less-than-ideal outcomes. Increasing total efficiency by integrating manufacturing and delivery scheduling processes is popular. This study focuses on synchronic production–distribution scheduling difficulties, particularly permutation flow shop scheduling in production and sequence-dependent setup time (SDST) and vehicle routing alternatives in distribution. To create a cost-effective distribution among the placement of geographically separated clients and hence to minimize delivery costs, batch delivery to customers employing a succession of homogenized capacity limitation vehicles is examined here. However, this might result in the failure to complete multiple client orders before their deadlines, raising the cost of lateness. As a result, the goal of this study is to lower the overall cost of tardiness and batch distribution in the supply chain. To accomplish so, a mixed-integer nonlinear programming model is developed, and the model is solved using a suggested genetic algorithm (GA). Because there is no established benchmark for this issue, a set of genuine problem scenarios is created in order to assess the proposed GA in a viable and difficult environment. Ruiz's benchmark data, which is derived from Taillard's benchmark cases of permutation flow shops, was supplemented with SDSTs in the production of test examples. In comparison to an exact method, the results show that the proposed GA can rapidly seek solutions to optimality for most small-sized instances. Furthermore, for medium and large-scale cases, the proposed GA continues to work well and produces solutions in a fair amount of time in comparison to GA without the local search.
Quantifying knapping actions: a method for measuring the angle of blow on flakes
Authors: Li Li , Reeves Jonathan S. , Lin Sam C. , Tennie Claudio , McPherron Shannon P.
Published: July 2022

Stone artifacts are critical for investigating the evolution of hominin behavior—they are among our only proxies for hominin behavior in deep time. Hominin cognition and skill are often inferred by reconstructing the technical decisions hominins made throughout the knapping process. However, despite many advancements in understanding how hominins knapped, some of the key factors involved in past flake production cannot be easily/readily derived from stone artifacts. In particular, the angle at which the knapper strikes the hammer against the core to remove the flake, or the angle of blow, is a key component of the knapping process that has up to now remained unmeasurable on archeological assemblages. In this study, we introduce a new method for estimating the angle of blow from the ventral surface of flakes. This method was derived from a controlled experiment that explicitly connects fracture mechanics to flake variability. We find that a feature of the flake’s bulb of percussion, what we call the bulb angle, is a measurable indicator of the angle of blow. Our experimental finding is further validated in two additional datasets from controlled and replicative knapping experiments. These results demonstrate the utility of continuing to link flake variation with technical decision-making to fracture mechanics. In addition, they also provide a useful and relatively simple means to capture a currently invisible aspect of hominin stone tool production behavior.
Impacts of climate-smart crop varieties and livestock breeds on the food security of smallholder farmers in Kenya
Authors: Radeny Maren , Rao Elizaphan J. O. , Ogada Maurice Juma , Recha John W. , Solomon Dawit
Published: July 2022

This paper analyses the impact of climate-smart agriculture (CSA) technologies on household dietary diversity and food insufficiency as indicators of food and nutrition security in Kenya. Using a combination of Propensity Score Matching and endogenous treatment effect approaches, we found that adoption of stress-tolerant varieties of several crops (such as bean, pigeon pea, cowpea, maize and sorghum) improved household dietary diversity score by 40% and reduced food insufficiency by 75%. Adoption of improved and resilient livestock breeds (including Red Maasai sheep and Galla goats) improved household dietary diversity by 38% while reducing household food insufficiency by 90%. We also found that stress-tolerant crop varieties were more effective in improving food security outcomes among households with large landholdings and with more educated and younger to middle-age heads. Effects of resilient livestock breeds on household food security were much stronger for households with large landholdings and with young and/or much older heads that have low levels of education. Given the large, demonstrated benefits from the use of the CSA technologies, policies and programs aimed at their promotion should apply appropriate targeting to ensure wider uptake of the technologies and maximum returns on investment.