bluuebunny/crossref_metadata_2025 huggingface dataset:
Cutaneous adverse events in children treated with vemurafenib for refractory BRAFV600E mutated Langerhans cell histiocytosis
Authors: Tardieu Mathilde , Néron Amélie , Duvert‐Lehembre Sophie , Amine Larabi Islam , Barkaoui Mohamed , Emile Jean‐Francois , Seigneurin Arnaud , Boralevi Franck , Donadieu Jean
Published: June 2021

Background

The somatic BRAFV600E mutation occurs in 38–64% of pediatric cases of Langerhans cell histiocytosis (LCH). Vemurafenib (VMF), a BRAF inhibitor, was approved for refractory BRAFV600E mutated LCH. In adults, VMF causes frequent cutaneous adverse events (CAE) including skin tumors (squamous cell carcinomas, melanomas), but little is known in children. The objective of this study was to evaluate the frequency, clinical spectrum, and severity of CAEs in children treated with VMF for LCH. In addition, a correlation between CAE occurrence and VMF dose, residual plasma levels (RPLs), and efficacy was searched for.

Procedure

Multicentric retrospective observational study including patients <18 years treated with VMF alone for refractory BRAFV600E mutated LCH in 13 countries between October 1, 2013 and December 31, 2018.

Results

Fifty‐seven patients: 56% female, median age 2.1 years (0.2–14.6), median treatment duration 4.1 months (1.4–29.7). Forty‐one patients (72%) had at least one CAE: photosensitivity (40%), keratosis pilaris (32%), rash (26%), xerosis (21%), and neutrophilic panniculitis (16%). No skin tumor was observed. Five percent of CAEs were grade 3. None were grade 4 or led to permanent VMF discontinuation. Dose reduction was necessary for 12% of patients, temporary treatment discontinuation for 16%, none leading to loss of efficacy. VMF dose, median RPL, and efficacy were not correlated with CAE occurrence.

Conclusions

At doses used for pediatric LCH, CAEs are frequent but rarely severe and have little impact on the continuation of treatment when managed appropriately. Regular dermatological follow‐up is essential to manage CAEs and screen for possible induced skin tumors.
Which eye are you looking through? The impact of cognitive bias on process safety
Authors: Kerin Trish
Published: June 2021

Bias surrounds us every day. Everything we look at has a lens of our experience coloring our perception, and everyone has their own lens. This impacts how we share and receive information. So why is this important for process safety? Cognitive biases cover a range of aspects, each of which can have an impact on process safety, from what we remember, to coping with too much information, to a lack of context and meaning or a need to act with great haste. There are many identified specific cognitive biases, not every one of them impacts on process safety, but many can and have. This paper will review several process safety type incidents that had cognitive bias as a factor and discuss ideas on how to manage the bias, so we do not fall into its trap.
Application of the Cox proportional hazards model and competing risks models to critical illness insurance data
Authors: Zapletal David
Published: June 2021

A commercial insurance company in the Czech Republic provided data on critical illness insurance. The survival analysis was used to study the influence of the gender of an insured person, the age at which the person entered into an insurance contract, and the region where the insured person lived on the occurrence of an insured event. The main goal of the research was to investigate whether the influence of explanatory variables is estimated differently when two different approaches of analysis are used. The two approaches used were (1) the Cox proportional hazard model that does not assign a specific cause, such as a certain diagnosis, to a critical illness insured event and (2) the competing risks models. Regression models related to these approaches were estimated by R software. The results, which are discussed and compared in the paper, show that insurance companies might benefit from offering policies that consider specific diagnoses as the cause of insured events. They also show that in addition to age, the gender of the client plays a key role in the occurrence of such insured events.
Synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones
Authors: Madikizela Balungile , Eckhardt Tamira , Goddard Richard , Richter Adrian , Lins Anika , Lehmann Christoph , Imming Peter , Seidel Rüdiger W.
Published: June 2021

8-Nitro-1,3-benzothiazin-4-ones (BTZs), with BTZ043 and PBTZ169 as the most advanced compounds, represent a new class of potent antitubercular agents, which irreversibly inhibit decaprenylphosphoryl-β-d-ribose-2′-epimerase (DprE1), an enzyme crucial for cell wall synthesis in the pathogen Mycobacterium tuberculosis. Synthesis, structural characterization and in vitro testing against Mycobacterium aurum DSM 43999 and M. tuberculosis H37Rv of halogenated 2-(4-ethoxycarbonylpiperazin-1-yl)-1,3-benzothiazin-4-ones lacking a nitro group are reported. X-ray crystallography reveals that the structure of the BTZ scaffold can significantly deviate from planarity. In contrast to recent reports, the results of the present study indicate that further investigation of halogenated non-nitro BTZs for antitubercular activity is less than a promising approach.
Lokales Wirbelsäulenprofil nach operativer Behandlung thorakolumbaler und lumbaler Frakturen
Authors: Ullrich Bernhard Wilhelm , Ottich Merle , Lawson McLean Aaron , Mendel Thomas , Hofmann Gunther Olaf , Schenk Philipp
Published: June 2021

Hintergrund

Ziel der Operation von Wirbelsäulenverletzungen ist eine stabile Ausheilung in physiologischer Stellung. Für offene und perkutane Operationen stehen unterschiedliche Techniken zur Verfügung.

Fragestellung

Das Ausmaß der offenen Reposition und das Retentionspotenzial der Techniken nach AOSpine (AT) und nach Kluger (KT) sollen verglichen werden. Der Einfluss von Frakturmorphologie, Alter, Geschlecht und Knochenqualität auf Reposition und Retention werden untersucht.

Material und Methoden

In dieser monozentrischen retrospektiven Kohortenstudie wurden Daten von Patienten mit traumatischen thorakolumbalen und lumbalen Frakturen untersucht, welche entweder mit AT oder KT reponiert wurden. Mittels bisegmentalen Grund-Deckplatten-Winkels (bGDW) wurde die Stellung des verletzten Wirbelsäulenabschnitts beschrieben. Normalwerte für die bGDW wurden anhand von Literaturdaten angenommen. Die Veränderung des bGDW im zeitlichen Verlauf wurde unter Einbeziehung der Knochenqualität in Hounsfield Units (HU), der Verletzungsschwere nach AOSpine und des Patientenalters und -geschlechts analysiert.

Ergebnisse

Es wurden 151 Datensätze ausgewertet. Beide Methoden reponieren vom Umfang nicht unterschiedlich (AT 10 ± 6°, KT 11 ± 8°; p = 0,786). Im Follow-up trat ein Korrekturverlust von −5 ± 4° auf. Die Technik (p = 0,998) hatte keinen Einfluss darauf. Die Frakturmorphologie zeigte einen knapp signifikanten Einfluss (p = 0,043). Niedrige HU korrelierten mit geringerem Repositionsumfang (r = 0,241, p < 0,003) und größerem Korrekturverlust (r = 0,272, p < 0,001) signifikant, aber schwach. In der Altersgruppe 50 bis 65 Jahre wiesen 21 % der Männer und 43 % der Frauen eine Knochenqualität von HU < 110 auf. Alter und HU korrelieren signifikant (r = −0,701, p < 0,001).

Diskussion

Die Techniken sind gleichwertig bezüglich der Repositions- und Retentionseigenschaften. Der hohe Anteil von Patienten mit HU < 110 in der Gruppe unter 65 Jahren bei Frauen und Männern und der Einfluss auf Reposition und Retention weisen auf die Notwendigkeit einer präoperativen Knochendichtemessung hin.
A Sobolev-Type Inequality for the Curl Operator and Ground States for the Curl–Curl Equation with Critical Sobolev Exponent
Authors: Mederski Jarosław , Szulkin Andrzej
Published: June 2021

Let $$\Omega \subset \mathbb {R}^3$$

Ω
⊂

R

3

be a Lipschitz domain and let $$S_\mathrm {curl}(\Omega )$$

S
curl

(
Ω
)

be the largest constant such that $$\begin{aligned} \int _{\mathbb {R}^3}|\nabla \times u|^2\, \mathrm{d}x\ge S_{\mathrm {curl}}(\Omega ) \inf _{\begin{array}{c} w\in W_0^6(\mathrm {curl};\mathbb {R}^3)\\ \nabla \times w=0 \end{array}}\Big (\int _{\mathbb {R}^3}|u+w|^6\,\mathrm{d}x\Big )^{\frac{1}{3}} \end{aligned}$$

∫

R

3

|
∇
×
u
|

2

d
x
≥

S
curl

(
Ω
)

inf

w
∈

W
0
6

(
curl
;

R

3

)

∇
×
w
=
0

(

∫

R

3

|
u
+
w
|

6

d
x

)

1
3

for any u in $$W_0^6(\mathrm {curl};\Omega )\subset W_0^6(\mathrm {curl};\mathbb {R}^3)$$

W
0
6

(
curl
;
Ω
)

⊂

W
0
6

(
curl
;

R

3

)

, where $$W_0^6(\mathrm {curl};\Omega )$$

W
0
6

(
curl
;
Ω
)

is the closure of $$\mathcal {C}_0^{\infty }(\Omega ,\mathbb {R}^3)$$

C
0
∞

(
Ω
,

R

3

)

in $$\{u\in L^6(\Omega ,\mathbb {R}^3): \nabla \times u\in L^2(\Omega ,\mathbb {R}^3)\}$$

{
u
∈

L
6

(
Ω
,

R

3

)

:
∇
×
u
∈

L
2

(
Ω
,

R

3

)

}

with respect to the norm $$(|u|_6^2+|\nabla \times u|_2^2)^{1/2}$$

(
|
u
|

6
2

+
|
∇
×
u
|

2
2

)

1
/
2

. We show that $$S_{\mathrm {curl}}(\Omega )$$

S
curl

(
Ω
)

is strictly larger than the classical Sobolev constant S in $$\mathbb {R}^3$$

R

3

. Moreover, $$S_{\mathrm {curl}}(\Omega )$$

S
curl

(
Ω
)

is independent of $$\Omega $$
Ω
and is attained by a ground state solution to the curl–curl problem $$\begin{aligned} \nabla \times (\nabla \times u) = |u|^4u \end{aligned}$$

∇
×

(
∇
×
u
)

=

|
u
|

4

u

if $$\Omega =\mathbb {R}^3$$

Ω
=

R

3

. With the aid of these results we also investigate ground states of the Brezis–Nirenberg-type problem for the curl–curl operator in a bounded domain $$\Omega $$
Ω
$$\begin{aligned} \nabla \times (\nabla \times u) +\lambda u = |u|^4u\quad \hbox {in }\Omega , \end{aligned}$$

∇
×

(
∇
×
u
)

+
λ
u
=

|
u
|

4

u

in

Ω
,

with the so-called metallic boundary condition $$\nu \times u=0$$

ν
×
u
=
0

on $$\partial \Omega $$

∂
Ω

, where $$\nu $$
ν
is the exterior normal to $$\partial \Omega $$

∂
Ω

.
Maturation of the Na,K-ATPase in the Endoplasmic Reticulum in Health and Disease
Authors: Kryvenko Vitalii , Vagin Olga , Dada Laura A. , Sznajder Jacob I. , Vadász István
Published: June 2021

The Na,K-ATPase establishes the electrochemical gradient of cells by driving an active exchange of Na+and K+ions while consuming ATP. The minimal functional transporter consists of a catalytic α-subunit and a β-subunit with chaperon activity. The Na,K-ATPase also functions as a cell adhesion molecule and participates in various intracellular signaling pathways. The maturation and trafficking of the Na,K-ATPase include co- and post-translational processing of the enzyme in the endoplasmic reticulum (ER) and the Golgi apparatus and subsequent delivery to the plasma membrane (PM). The ER folding of the enzyme is considered as the rate-limiting step in the membrane delivery of the protein. It has been demonstrated that only assembled Na,K-ATPase α:β-complexes may exit the organelle, whereas unassembled, misfolded or unfolded subunits are retained in the ER and are subsequently degraded. Loss of function of the Na,K-ATPase has been associated with lung, heart, kidney and neurological disorders. Recently, it has been shown that ER dysfunction, in particular, alterations in the homeostasis of the organelle, as well as impaired ER-resident chaperone activity may impede folding of Na,K-ATPase subunits, thus decreasing the abundance and function of the enzyme at the PM. Here, we summarize our current understanding on maturation and subsequent processing of the Na,K-ATPase in the ER under physiological and pathophysiological conditions.

Graphic Abstract
Potentially Avertable Child Mortality Associated with Surgical Workforce Scale‐up in Low‐ and Middle‐Income Countries: A Global Study
Authors: Truche Paul , Botelho Fabio , Bowder Alexis N. , Levis Alexander W. , Greenberg Sarah L. M. , Smith Emily , Corlew Scott , Bickler Stephen , Rice Henry E. , Ameh Emmanuel A. , Meara John G. , Poenaru Dan , Mooney David P. ,   the Global Initiative for Children's Surgery
Published: June 2021

Background

Expansion of access to surgical care can improve health outcomes, although the impact that scale‐up of the surgical workforce will have on child mortality is poorly defined. In this study, we estimate the number of child deaths potentially avertable by increasing the surgical workforce globally to meet targets proposed by the Lancet Commission on Global Surgery.

Methods

To estimate the number of deaths potentially avertable through increases in the surgical workforce, we used log‐linear regression to model the association between surgeon, anesthetist and obstetrician workforce (SAO) density and surgically amenable under‐5 mortality rate (U5MR), infant mortality rate (IMR), and neonatal mortality rate (NMR) for 192 countries adjusting for potential confounders of childhood mortality, including the non‐surgical workforce (physicians, nurses/midwives, community health workers), gross national income per capita, poverty rate, female literacy rate, health expenditure per capita, percentage of urban population, number of surgical operations, and hospital bed density. Surgically amenable mortality was determined using mortality estimates from the UN Inter‐agency Group for Child Mortality Estimation adjusted by the proportion of deaths in each country due to communicable causes unlikely to be amenable to surgical care. Estimates of mortality reduction due to upscaling surgical care to support the Lancet Commission on Global Surgery (LCoGS) minimum target of 20–40 SAO/100,000 were calculated accounting for potential increases in surgical volume associated with surgical workforce expansion.

Results

Increasing SAO workforce density was independently associated with lower surgically amenable U5MR as well as NMR (p < 0.01 for each model). When accounting for concomitant increases in surgical volume, scale‐up of the surgical workforce to 20–40 SAO/100,000 could potentially prevent between 262,709 (95% CI 229,643–295,434) and 519,629 (465,046–573,919) under 5 deaths annually. The majority (61%) of deaths averted would be neonatal deaths.

Conclusion

Scale up of surgical workforce may substantially decrease childhood mortality rates around the world. Our analysis suggests that scale‐up of surgical delivery through increase in the SAO workforce could prevent over 500,000 children from dying before the age of 5 annually. This would represent significant progress toward meeting global child mortality reduction targets.
Anthropogenic activities are associated with shorter telomeres in chicks of Adélie penguin (Pygoscelis adeliae)
Authors: Caccavo Jilda Alicia , Raclot Thierry , Poupart Timothée , Ropert-Coudert Yan , Angelier Frédéric
Published: June 2021

Defining the impact of anthropogenic stressors on Antarctic wildlife is an active aim for investigators. Telomeres represent a promising molecular tool to investigate the fitness of wild populations, as their length may predict longevity and survival. We examined the relationship between telomere length and human exposure in Adélie penguin chicks (Pygoscelis adeliae) from East Antarctica. Telomere length was compared between chicks from areas with sustained human activity and on neighboring protected islands with little or no human presence. Adélie penguin chicks from sites exposed to human activity had significantly shorter telomeres than chicks from unexposed sites in nearby protected areas, with exposed chicks having on average 3.5% shorter telomeres than unexposed chicks. While sampling limitations preclude our ability to draw more sweeping conclusions at this time, our analysis nonetheless provides important insights into measures of colony vulnerability. More data are needed both to understand the proximate causes (e.g., stress, feeding events) leading to shorter telomeres in chicks from human exposed areas, as well as the fitness consequences of reduced telomere length. We suggest to further test the use of telomere length analysis as an eco-indicator of stress in wildlife among anthropized sites throughout Antarctica.
Correction to: Describing a new food group classification system for UK biobank: analysis of food groups and sources of macro- and micronutrients in 208,200 participants
Authors: Piernas Carmen , Perez-Cornago Aurora , Gao Min , Young Heather , Pollard Zoe , Mulligan Angela , Lentjes Marleen , Carter Jennifer , Bradbury Kathryn , Key Tim J. , Jebb Susan A.
Published: June 2021

A correction to this paper has been published: https://doi.org/10.1007/s00394-021-02591-3
Kurt Jellinger 90: his contribution to neuroimmunology
Authors: Dal-Bianco Assunta , Höftberger Romana , Lassmann Hans , Berger Thomas
Published: June 2021

This review honors Kurt Jellinger on his 90th birthday as one of the most outstanding neuropathologists, who has contributed immensely to neuroscience due to his vast experience and collection of excellently documented autopsy cases. Two of his many insightful reports are highlighted here. One report focuses on the pathogenesis of inflammatory demyelinating diseases and investigates the neuropathology in autopsy tissue of a patient, who developed an MS-like disease after repeated treatment with lyophilized bovine brain cells in 1958. More than 60 years later, after reinvestigation of the historic samples in 2015 and subsequent mRNA isolation, next generation sequencing and reconstruction of the antibody, we succeeded in identifying myelin oligodendrocyte glycoprotein (MOG) as the target antigen and provided the missing element between the pathomechanisms in classic EAE animal models and transfer of this disease process into humans. A second significant example of Kurt Jellinger’s contribution to neuroscience was a report on the role of MS in the development of Alzheimer's disease (AD), which found that AD pathology is present to the same extent in demyelinated and non-demyelinated cortical areas in MS and the incidence for AD pathology in elderly MS patients is comparable to the normal-aging population. This indicates that chronic inflammation in the MS cortex alone does not significantly predispose to the development of cortical AD pathology. These and other findings were only possible due to the broad collection of extremely well-defined material established by Kurt Jellinger, which ultimately continues to contribute to translational neuroscience, even decades later.
Spin Labeling of Surface Cysteines Using a Bromoacrylaldehyde Spin Label
Authors: Heaven Graham , Hollas Michael A. , Tabernero Lydia , Fielding Alistair J.
Published: June 2021

Structural investigations of proteins and their biological complexes are now frequently complemented by distance constraints between spin labeled cysteines generated using double electron–electron resonance (DEER) spectroscopy, via site directed spin labeling (SDSL). Methanethiosulfonate spin label (MTSSL), has become ubiquitous in the SDSL of proteins, however, has limitations owing to its high number of rotamers, and reducibility. In this article we introduce the use of bromoacrylaldehyde spin label (BASL) as a cysteine spin label, demonstrating an advantage over MTSSL due to its increased selectivity for surface cysteines, eliminating the need to ‘knock out’ superfluous cysteine residues. Applied to the multidomain protein, His domain protein tyrosine phosphatase (HD-PTP), we show that BASL can be easily added in excess with selective labeling, whereas MTSSL causes protein precipitation. Furthermore, using DEER, we were able to measure a single cysteine pair distance in a three cysteine domain within HD-PTP. The label has a further advantage of comprising a sulfide in a three-bond tether, making it a candidate for protein binding and in-cell studies.
Quantifying activities of daily living impairment in Parkinson’s disease using the Functional Activities Questionnaire
Authors: Becker Sara , Pauly Claire , Lawton Michael , Hipp Geraldine , Bowring Francesca , Sulzer Patricia , Hu Michele , Krüger Rejko , Gasser Thomas , Liepelt-Scarfone Inga
Published: June 2021

Objective

Cognitive-driven activity of daily living (ADL) impairment in Parkinson’s disease (PD) is increasingly discussed as prodromal marker for dementia. Diagnostic properties of assessments for this specific ADL impairment are sparsely investigated in PD. The ability of the Functional Activities Questionnaire (FAQ) for differentiating between PD patients with normal cognition and with mild cognitive impairment (PD-MCI), according to informant and self-reports, was examined. Global cognitive function in groups with and without mild ADL impairment was compared according to different cut-offs.

Methods

Multicenter data of 589 patients of an international cohort (CENTRE-PD) were analyzed. Analyses were run separately for informant-rated and self-rated FAQ. Receiver operating characteristic (ROC) analysis was conducted to define the optimal FAQ cut-off for PD-MCI (≥ 1), and groups were additionally split according to reported FAQ cut-offs for PD-MCI in the literature (≥ 3, ≥ 5). Binary logistic regressions examined the effect of the Montreal Cognitive Assessment (MoCA) score in PD patients with and without mild ADL impairment.

Results

Two hundred and twenty-five (38.2%) patients were classified as PD-MCI. For all three cut-off values, sensitivity was moderate to low (< 0.55), but specificity was moderately high (> 0.54) with a tendency of higher values for self-reported deficits. For the self-report, the cut-off ≥ 3 showed a significant effect of the MoCA (B =  − 0.31, p = 0.003), where FAQ ≥ 3 patients had worse cognition. No effect for group differences based on informant ratings was detected.

Conclusion

Our data argue that self-reported ADL impairments assessed by the FAQ show a relation to the severity of cognitive impairment in PD.
Socioeconomic disparities in climate vulnerability: neonatal mortality in northern Sweden, 1880–1950
Authors: Karlsson Lena , Junkka Johan , Schumann Barbara , Lundevaller Erling Häggström
Published: June 2021

The aim of this study was to analyse the association between season of birth, temperature and neonatal mortality according to socioeconomic status in northern Sweden from 1880 to 1950. The source material for this study comprised digitised parish records combined with local weather data. The association between temperature, seasonality, socioeconomic status and neonatal mortality was modelled using survival analysis. We can summarise our findings according to three time periods. During the first period (1880–1899), temperature and seasonality had the greatest association with high neonatal mortality, and the socioeconomic differences in vulnerability were small. The second period (1900–1929) was associated with a decline in seasonal and temperature-related vulnerabilities among all socioeconomic groups. For the last period (1930–1950), a new regime evolved with rapidly declining neonatal mortality rates involving class-specific temperature vulnerabilities, and there was a particular effect of high temperature among workers. We conclude that the effect of season of birth on neonatal mortality was declining for all socioeconomic groups (1880–1950), whereas weather vulnerability was pronounced either when the socioeconomic disparities in neonatal mortality were large (1880–1899) or during transformations from high to low neonatal rates in the course of industrialisation and urbanisation.
Shaken and Stirred: When Bond Meets Suess–de Vries and Gnevyshev–Ohl
Authors: Stefani F. , Stepanov R. , Weier T.
Published: June 2021

We argue that the most prominent temporal features of the solar dynamo, in particular the Hale cycle, the Suess–de Vries cycle (associated with variations of the Gnevyshev–Ohl rule), Gleissberg-type cycles, and grand minima can all be explained by combined synchronization with the 11.07-year periodic tidal forcing of the Venus–Earth–Jupiter system and the (mainly) 19.86-year periodic motion of the Sun around the barycenter of the solar system. We present model simulations where grand minima, and clusters thereof, emerge as intermittent and non-periodic events on millennial time scales, very similar to the series of Bond events which were observed throughout the Holocene and the last glacial period. If confirmed, such an intermittent transition to chaos would prevent any long-term prediction of solar activity, notwithstanding the fact that the shorter-term Hale and Suess–de Vries cycles are clocked by planetary motion.
Game of Cruxes: co-designing a game for scientists and stakeholders for identifying joint problems
Authors: Salliou Nicolas , Bruley Enora , Moreau Clémence , Luthe Tobias , Blanco Victor , Lavorel Sandra , Grêt-Regamey Adrienne
Published: June 2021

Scientists increasingly cross their disciplinary boundaries and connect with local stakeholders to jointly solve complex problems. Working with stakeholders means higher legitimacy and supports practical impact of research. Games provide a tool to achieve such transdisciplinary collaboration. In this paper, we explore the use of a game in a participatory project where scientists and local stakeholders are seeking and defining a joint problem. The literature is clear that this step is essential but remains short on concrete methods. Here, we explore this potential in practice. We conducted parallel participatory processes in two alpine regions considered as socio-ecological system (SES) in Switzerland and France, both vulnerable to global change. Based on these two case studies, we co-constructed a game, integrating scientific concerns about key land use, climate change and socio-economic elements of a mountain SES (tourism, agriculture, housing and demography). With the game, we assessed the existence of joint problems connecting scientific and local interests. The game successfully engaged participants at both sites over 11 game sessions, showing potential of use in other transdisciplinary settings. By covering a wide array of issues, the game created a discussion space for listing problems and identifying where scientist and stakeholder interests overlap. In Switzerland, the game revealed no pressing joint problem to be addressed. In France, game sessions revealed, among other problems, an enduring and complex issue regarding the co-existence of inhabitants and powerful institutions. Having demonstrated the capacity of this game for joint-problem assessment, we believe other participatory research in similar SES could benefit from an early use of such an approach to frame the potential for collaboration.
Current management of cancer-associated venous thromboembolism in patients with thrombocytopenia: a retrospective cohort study
Authors: Squizzato Alessandro , Galliazzo Silvia , Rancan Elena , Di Pilla Marina , Micucci Giorgia , Podda Gianmarco , Valeriani Emanuele , Campiotti Leonardo , Bertù Lorenza , Ageno Walter , Porreca Ettore , Lodigiani Corrado
Published: June 2021

Optimal management of venous thromboembolism (VTE) in cancer patients with thrombocytopenia is uncertain. We described current management and clinical outcomes of these patients. We retrospectively included a cohort of cancer patients with acute VTE and concomitant mild (platelet count 100,000–150,000/mm3), moderate (50,000–99,000/mm3), or severe thrombocytopenia (< 50,000/mm3). Univariate and multivariate logistic regression analyses explored the association between different therapeutic strategies and thrombocytopenia. The incidence of VTE and bleeding complications was collected at a 3-month follow-up. A total of 194 patients of whom 122 (62.89%) had mild, 51 (26.29%) moderate, and 22 (11.34%) severe thrombocytopenia were involved. At VTE diagnosis, a full therapeutic dose of LMWH was administered in 79.3, 62.8 and 4.6% of patients, respectively. Moderate (OR 0.30; 95% CI 0.12–0.75), severe thrombocytopenia (OR 0.01; 95% CI 0.00–0.08), and the presence of cerebral metastasis (OR 0.06; 95% CI 0.01–0.30) were independently associated with the prescription of subtherapeutic LMWH doses. Symptomatic VTE (OR 4.46; 95% CI 1.85–10.80) and pulmonary embolism (OR 2.76; 95% CI 1.09–6.94) were associated with the prescription of full therapeutic LMWH doses. Three-month incidence of VTE was 3.9% (95% CI 1.3–10.1), 8.5% (95% CI 2.8–21.3), 0% (95% CI 0.0–20.0) in patients with mild, moderate, and severe thrombocytopenia, respectively. The corresponding values for major bleeding and mortality were 1.9% (95% CI 0.3–7.4), 6.4% (95% CI 1.7–18.6), 0% (95% CI 0.0–20.0) and 9.6% (95% CI 5.0–17.4), 48.2% (95% CI 16.1–42.9), 20% (95% CI 6.6–44.3). In the absence of sound evidence, anticoagulation strategy of VTE in cancer patients with thrombocytopenia was tailored on an individual basis, taking into account not only the platelet count but also VTE presentation and the presence of cerebral metastasis.
The Nephroprotective Properties of Extracellular Vesicles in Experimental Models of Chronic Kidney Disease: a Systematic Review
Authors: Nowak Natalia , Yamanouchi Masayuki , Satake Eiichiro
Published: June 2021

Extracellular vesicle (EV)-based therapy was hypothesized as a promising regenerative approach which has led to intensive research of EVs in various pathologies. In this study, we performed a comprehensive systematic review of the current experimental evidence regarding the protective properties of EVs in chronic kidney disease (CKD). We evaluated the EV-based experiments, EV characteristics, and effector molecules with their involvement in CKD pathways. Including all animal records with available creatinine or urea data, we performed a stratified univariable meta-analysis to assess the determinants of EV-based therapy effectiveness. We identified 35 interventional studies that assessed nephroprotective role of EVs and catalogued them according to their involvement in CKD mechanism. Systematic assessment of these studies suggested that EVs had consistently improved glomerulosclerosis, interstitial fibrosis, and cell damage, among different CKD models. Moreover, EV-based therapy reduced the progression of renal decline in CKD. The stratified analyses showed that the disease model, administered dose, and time of therapeutic intervention were potential predictors of therapeutic efficacy. Together, EV therapy is a promising approach for CKD progression in experimental studies. Further standardisation of EV-methods, continuous improvement of the study quality, and better understanding of the determinants of EV effectiveness will facilitate preclinical research, and may help development of clinical trials in people with CKD.

Graphical Abstract
Does Impaired Glymphatic Drainage Cause Glymphedema? A Review Tailored to Neurocritical Care and Neurosurgery
Authors: Akins Paul T. , Guppy Kern H.
Published: June 2021

Research into the glymphatic system reached an inflection point with steep trajectory in 2012 when it was formally recognized and named, but the historical roots for it are solid and deep, dating back to pioneers such as Cushing, Weed, and Dandy. We provide an overview of key discoveries of the glymphatic system, which promotes bulk flow of fluid and solutes throughout the brain parenchyma. We also discuss the lymphatic drainage of the central nervous system. Evidence is building that failure of the glymphatic system causes glymphedema in patients commonly managed by neurocritical care and neurosurgery specialists. We review research supporting this for decompressive craniectomy, subarachnoid hemorrhage, and normal-pressure hydrocephalus. We argue that it is time for a paradigm shift from the traditional model of cerebrospinal fluid circulation to a revised model that incorporates the glymphatic pathway and lymphatic clearance. These recent breakthroughs will inspire new therapeutic approaches to recognize, reverse, and restore glymphatic dysfunction and to leverage this pathway to deliver brain-wide therapeutics.
Complicity of α-synuclein oligomer and calcium dyshomeostasis in selective neuronal vulnerability in Lewy body disease
Authors: Yamamoto Kenji
Published: June 2021

α-Synuclein oligomers and Ca2+ dyshomeostasis have been thoroughly investigated with respect to the pathogenesis of Lewy body disease (LBD). In LBD, α-synuclein oligomers exhibit a neuron-specific cytoplasmic distribution. Highly active neurons and neurons with a high Ca2+ burden are prone to damage in LBD. The neuronal vulnerability may be determined by transneuronal axonal transmission of the pathological processes; however, this hypothesis seems inconsistent with pathological findings that neurons anatomically connected to LBD-vulnerable neurons, such as neurons in the ventral tegmentum, are spared in LBD. This review focuses on and discusses the crucial roles played by α-synuclein oligomers and Ca2+ dyshomeostasis in early intraneural pathophysiology in LBD-vulnerable neurons. A challenging view is proposed on the synergy between retrograde transport of α-synuclein and vesicular Ca release, whereby neuronal vulnerability is propagated backward along repeatedly activated signaling pathway.
Termitomenins F and G, Two New Lignan Glucosides from Terminalia chebula var. tomentella (Kurz) C. B. Clarke
Authors: Yin Jun , Zhu Hong-Tao , Zhang Man , Wang Dong , Yang Chong-Ren , Zhang Ying-Jun
Published: June 2021

The extensive chemical investigation on the branches and leaves ofTerminalia chebulavar.tomentella(Combretaceae) led to the isolation of two new lignan glucosides with a furofuran skeleton, termitomenins F (1) and G (2). In addition, 19 known compounds including five lignan glucosides (3–7), six hydrolyzable tannins (8–13) and eight simple phenolics (14–21) were also identified. Their structures were determined by comprehensive spectroscopic analyses. It is noted that8and9wereC-glycosidic hydrolyzable tannins with one hexahydroxydiphenoyl and one gallagyl group linked to an open-chain glucosylC-1/O-2/O-3 andO-4/O-6, respectively, which were rarely found in plants. Nine known compounds,6–9,13, and18–21, were procured from the titled plant for the first time, while3–5,10–12and14–17were also found in the fruits. Notably, the known hydrolyzable tannins8–13exhibited stronger α-glucosidase inhibitory activities with IC50values ranging from 0.10 to 3.12 μM, than the positive control, quercetin (IC50 = 9.38 ± 0.33 μM).

Graphic abstract
An update of treatment modalities in children and adolescents with teeth affected by molar incisor hypomineralisation (MIH): a systematic review
Authors: Somani C. , Taylor G. D. , Garot E. , Rouas P. , Lygidakis N. A. , Wong F. S. L.
Published: June 2021

Purpose

To systematically review the treatment modalities for molar-incisor hypomineralisation for children under the age of 18 years. The research question was, ‘What are the treatment options for teeth in children affected by molar incisor hypomineralisation?’

Methods

An electronic search of the following electronic databases was completed MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, LILACS, Google Scholar and Open Grey identifying studies from 1980 to 2020. The PRISMA guidelines were followed. The studies were screened, data extracted and calibration was completed by two independent reviewers.

Results

Of 6220 potential articles, 34 studies were included. Twenty studies investigated management of molars with fissure sealants, glass ionomer cement, polyacid modified resin composite, composite resin, amalgam, preformed metal crowns, laboratory-manufactured crowns and extractions. In four articles management of incisors with microabrasion, resin-infiltration and a combination of approaches was reported. Eight studies looked at strategies to mineralise MIH-affected teeth and/or reduce hypersensitivity. Two studies investigated patient-centred outcomes following treatment. Due to the heterogeneity between the studies, meta-analysis was not performed.

Conclusion

The use of resin-based fissure sealants, preformed metal crowns, direct composite resin restorations and laboratory-made restorations can be recommended for MIH-affected molars. There is insufficient evidence to support specific approaches for the management of affected incisors. Products containing CPP-ACP may be beneficial for MIH-affected teeth.
High order singular value decomposition for plant diversity estimation
Authors: Bernardi Alessandra , Iannacito Martina , Rocchini Duccio
Published: June 2021

We propose a new method to estimate plant diversity with Rényi and Rao indexes through the so called High Order Singular Value Decomposition (HOSVD) of tensors. Starting from NASA multi-spectral images we evaluate diversity and we compare original diversity estimates with those realized via the HOSVD compression methods for big data. Our strategy turns out to be extremely powerful in terms of memory storage and precision of the outcome. The obtained results are so promising that we can support the efficiency of our method in the ecological framework.
License plate identification and recognition in a non-standard environment using neural pattern matching
Authors: Shafi Imran , Hussain Imtiaz , Ahmad Jamil , Kim Pyoung Won , Choi Gyu Sang , Ashraf Imran , Din Sadia
Published: June 2021

Non-standard license plates are a part of current traffic trends in Pakistan. Private number plates should be recognized and, monitored for several purposes including security as well as a well-developed traffic system. There is a challenging task for the authorities to recognize and trace the locations for the certain number plate vehicle. In a developing country like Pakistan, it is tough to have higher constraints on the efficiency of any license plate identification and recognition algorithm. Character recognition efficiency should be a route map for the achievement of the desired results within the specified constraints. The main goal of this study is to devise a robust detection and recognition mechanism for non-standard, transitional vehicle license plates generally found in developing countries. Improvement in the character recognition efficiency of drawn and printed plates in different styles and fonts using single using multiple state-of-the-art technologies including machine-learning (ML) models. For the mentioned study, 53-layer deep convolutional neural network (CNN) architecture based on the latest variant of object detection algorithm-You Only Look Once (YOLOv3) is employed. The proposed approach can learn the rich feature representations from the data of diversified license plates. The input image is first pre-processed for quality improvement, followed by dividing it into suitable-sized grid cells to find the correct location of the license plate. For training the CNN, license plate characters are segmented. Lastly, the results are post-processed and the accuracy of the proposed model is determined through standard benchmarks. The proposed method is successfully tested on a large image dataset consisting of eight different types of license plates from different provinces in Pakistan. The proposed system is expected to play an important role in implementing vehicle tracking, payment for parking fees, detection of vehicle over-speed limits, reducing road accidents, and identification of unauthorized vehicles. The outcome shows that the proposed approach achieves a plate detection accuracy of 97.82% and the character recognition accuracy of 96%.
Changes in properties of tar obtained during underground coal gasification process
Authors: Wiatowski Marian , Muzyka Roksana , Kapusta Krzysztof , Chrubasik Maciej
Published: June 2021

In this study, the composition of tars collected during a six-day underground coal gasification (UCG) test at the experimental mine ‘Barbara’ in Poland in 2013 was examined. During the test, tar samples were taken every day from the liquid product separator and analysed by the methods used for testing properties of typical coke oven (coal) tar. The obtained results were compared with each other and with the data for coal tar. As gasification progressed, a decreasing trend in the water content and an increasing trend in the ash content were observed. The tars tested were characterized by large changes in the residue after coking and content of parts insoluble in toluene and by smaller fluctuations in the content of parts insoluble in quinoline. All tested samples were characterized by very high distillation losses, while for samples starting from the third day of gasification, a clear decrease in losses was visible. A chromatographic analysis showed that there were no major differences in composition between the tested tars and that none of the tar had a dominant component such as naphthalene in coal tar. The content of polycyclic aromatic hydrocarbons (PAHs) in UCG tars is several times lower than that in coal tar. No light monoaromatic hydrocarbons (benzene, toluene, ethylbenzene and xylenes—BTEX) were found in the analysed tars, which results from the fact that these compounds, due to their high volatility, did not separate from the process gas in the liquid product separator.
Schilddrüse und Schwangerschaft
Authors: Bojunga Jörg , Hofbauer Ludwig
Published: June 2021

Die Schilddrüsenfunktion spielt eine wichtige Rolle nicht nur in der Entwicklung des Fetus, sondern bereits präkonzeptionell. Eine Kontrolle des TSH-Werts vor Schwangerschaftsbeginn ist insbesondere bei unerfülltem Kinderwunsch sowie bekannter Schilddrüsenhormonsubstitution sinnvoll, um einen möglicherweise bestehenden Substitutionsbedarf zu erkennen und entsprechend auszugleichen. Bei erfolgreicher Konzeption lässt sich ein typischer, trimenonspezifischer Verlauf der Schilddrüsenaktivität beobachten, welcher beeinflusst ist durch schwangerschaftsbedingte Hormonveränderungen. Physiologisch sind ein TSH-Abfall im 1. Trimenon, der selten in eine transiente Gestationshyperthyreose übergehen kann, sowie ein geringgradiger Abfall der fT4-Konzentration im 3. Trimenon. Abzugrenzen von physiologischen Veränderungen der Schilddrüsenhormonkonstellation in der Schwangerschaft sind die eine Behandlung erforderlich machende Hypo- und Hyperthyreose. Sowohl eine Schilddrüsenüber- als auch eine Schilddrüsenunterfunktion hat potenziell schädigende Auswirkungen auf das Ungeborene. Eine therapiebedürftige Hypothyreose in der Schwangerschaft ist mit abhängig vom vorliegenden Antikörperstatus und sollte in Abhängigkeit vom TSH-Wert über die Schwangerschaft hinweg kontrolliert und angepasst werden. Eine weitere besondere Herausforderung besteht bei Notwendigkeit einer thyreostatischen Therapie, beispielsweise im Rahmen eines Morbus Basedow. Hier gilt es, aufgrund der Nebenwirkungsprofile zur Verfügung stehender Thyreostatika trimenonspezifische Medikamentenwechsel zu vollziehen. Der folgende Artikel soll anhand aktueller Daten einen Überblick über aktuelle schilddrüsenbezogene Therapie- und Diagnostikempfehlungen in der Schwangerschaft geben.
Role of Bi3+ ions on structural, optical, photoluminescence and electrical performance of Cd0.9-xZn0.1BixS QDs
Authors: Krishnamoorthy A. , Sakthivel P. , Devadoss I. , Rajathi V. M. Anitha
Published: June 2021

In this work, the Cd0.9-xZn0.1BixS QDs with different compositions of Bi3+ ions (0 ≤ x ≤ 0.05) were synthesized using a facile chemical route. The prepared QDs were characterized for analyzing the structural, morphological, elemental, optical, band gap, photoluminescence and electrochemical properties. XRD results confirmed that the Cd0.9-xZn0.1BixS QDs have a cubic structure. The mean crystallite size was increased from ~ 2 to ~ 5 nm for the increase of Bi3+ ions concentration. The optical transmittance behavior was decreased with increasing Bi3+ ions. The scanning electron microscope images showed that the prepared QDs possessed agglomerated morphology and the EDAX confirmed the presence of doped elements as per stoichiometry ratio. The optical band gap was slightly blue-shifted for initial substitution (Bi3+  = 1%) of Bi3+ ions and red-shifted for further increase of Bi3+ compositions. The optical band gap was ranged between 3.76 and 4.0 eV. High intense red emission was received for Bi3+ (1%) doped Zn:CdS QDs. The red emission peaks were shifted to a higher wavelength side due to the addition of Bi3+ ions. The PL emission on UV-region was raised for Bi3+ (1%) and it was diminished. Further, a violet (422 nm) and blue (460 nm) emission were received for Bi3+ ions doping. The cyclic voltammetry analysis showed that Bi3+ (0%) possessed better electrical properties than other compositions of Bi3+ ions.
Phenotypic and genotypic characterization of mcr-1-positive multidrug-resistant Escherichia coli ST93, ST117, ST156, ST10, and ST744 isolated from poultry in Poland
Authors: Ćwiek Katarzyna , Woźniak-Biel Anna , Karwańska Magdalena , Siedlecka Magdalena , Lammens Christine , Rebelo Ana Rita , Hendriksen Rene S. , Kuczkowski Maciej , Chmielewska-Władyka Monika , Wieliczko Alina
Published: June 2021

Background

A plasmid-mediated mechanism of bacterial resistance to polymyxin is a serious threat to public health worldwide. The present study aimed to determine the occurrence of plasmid-mediated colistin resistance genes and to conduct the molecular characterization of mcr-positive Escherichia coli strains isolated from Polish poultry.

Methods

In this study, 318 E. coli strains were characterized by the prevalence of mcr1–mcr5 genes, antimicrobial susceptibility testing by minimal inhibitory concentration method, the presence of antimicrobial resistance genes was screened by PCR, and the biofilm formation ability was tested using the crystal violet staining method. Genetic relatedness of mcr-1-positive E. coli strains was evaluated by multilocus sequence typing method.

Results

Among the 318 E. coli isolates, 17 (5.35%) harbored the mcr-1 gene. High antimicrobial resistance rates were observed for ampicillin (100%), tetracycline (88.24%), and chloramphenicol (82.35%). All mcr-1-positive E. coli strains were multidrug-resistant, and as many as 88.24% of the isolates contained the blaTEM gene, tetracycline (tetA and tetB), and sulfonamide (sul1, sul2, and sul3) resistance genes. Additionally, 41.18% of multidrug-resistant, mcr-1-positive E. coli isolates were moderate biofilm producers, while the rest of the strains showed weak biofilm production. Nine different sequence types were identified, and the dominant ST was ST93 (29.41%), followed by ST117 (17.65%), ST156 (11.76%), ST 8979 (11.76%), ST744 (5.88%), and ST10 (5.88%). Moreover, the new ST was identified in this study.

Conclusions

Our results showed a low occurrence of mcr-1-positive E. coli strains isolated from Polish poultry; however, all the isolated strains were resistant to multiple antimicrobial agents and were able to form biofilms at low or medium level.
Leader Nationalism, Ethnic Identity, and Terrorist Violence
Authors: Choi Seung-Whan
Published: June 2021

Whether or not nationalism fuels terrorist violence by ethnic groups is an important yet underexplored research question. This study offers a theoretical argument, empirical analysis and a case study. When political leaders such as presidents and prime ministers use nationalism to shore up legitimacy, they threaten the existence of disfavored ethnic groups. In turn, those groups are more likely to respond with terrorist attacks. The author tests this argument using a sample of 766 ethnic groups across 163 countries from 1970 to 2009. The multilevel mixed-effects negative binomial regression results provide evidence that leader nationalism is a significant driver of ethnic terrorism. The detrimental effect of nationalism remains the same after using a generalized method of moments method to account for possible reverse causality. A case study of Sinhalese nationalist leaders versus Tamil Tigers also supports the nationalism and terrorism nexus.
Is Aristotle the Forefather of Informal Logic?
Authors: Groarke Louis F.
Published: June 2021

I argue that Aristotle takes a ‘natural language semantics’ approach to logic, which is consistent with the general attitudes one finds in informal logic today. Although his position is complex, Aristotle emphasizes the intensional rather than the extensional side of argument evaluation. He does not take a truth-functional approach to semantics, but an approach that elucidates the illative mechanism through an understanding of natures. This comes close to what informal logicians insist on. The informal logic movement was, to a very large extent, a Canadian initiative, prominently featuring authors such as Johnson, Blair, Govier, and many others.