bluuebunny/crossref_metadata_2025 huggingface dataset:
Anomaly-free axion dark matter in three Higgs doublet model and its phenomenological implications
Authors: Sakurai Kodai , Takahashi Fuminobu
Published: July 2022

Abstract

We study phenomenological implications of an axion that arises as a pseudo Nambu-Goldstone boson due to the spontaneous breaking of anomaly-free global flavor symmetry. One interesting possibility for such anomaly-free axion to explain dark matter (DM) is when it has a mass of order keV and an intermediate scale decay constant, since it can be explored through direct search experiments, X-ray observations, various stellar cooling processes, and the misalignment mechanism naturally explains the DM abundance. As a concrete renormalizable model of such axion, we consider an extended Higgs sector with global flavor symmetry, which consists of three Higgs doublet fields and three singlet Higgs fields with U(1)B−L charges. We identify viable parameter regions that satisfy theoretical bounds on the Higgs potential and various experimental limits on this model, and evaluate the mass spectra of the axion and extra Higgs bosons. We find that even an anomaly-free axion can generally couple to photons through mixing with CP-odd Higgs, and that its strength depends on the vacuum expectation values of the Higgs doublets as well as the axion mass. As a result, the ratios of the vacuum expectation values of the Higgs doublets are tightly constrained to satisfy the X-ray constraints. We show the favored parameter region where axion DM explains the XENON1T excess. We also demonstrate that the axion-electron coupling is correlated with the extra Higgs boson masses and mixing angles for CP-even Higgs bosons. Thus, if the axion is detected in future observations, the extra Higgs boson masses and the coupling of the standard model-like Higgs boson with the weak gauge bosons are restricted. This is a good example of the synergy between searches for the axion DM and the BSM around the electroweak scale.
On a multiplicative distribution of functions in complex plane
Authors: Bartoszek Bartosz , Długosz Renata
Published: July 2022

In the paper there are two kinds of functional symmetry considered, i.e., (1)-power symmetry and $$(-1)$$

(
-
1
)

-power symmetry, in a rich subfamily $$\mathcal {B}$$
B
of the family of all complex valued functions on a symmetric set $$\mathcal {G}\subset \mathbb {C}$$

G
⊂
C

. The first one defines the values $$f(-z)$$

f
(
-
z
)

as identical with f(z) and the other as the inverse of the f(z) in $$\mathcal {G}$$
G
. The announced notions allow a unique decomposition of functions $$f\in \mathcal {B}$$

f
∈
B

into a product of two factors $$f_{1},f_{-1}$$

f
1

,

f

-
1

having the (1)- and the $$(-1)$$

(
-
1
)

-power symmetry property, respectively. In the paper there are also given examples of such partitions $$f=f_{1}\cdot f_{-1}$$

f
=

f
1

·

f

-
1

, for various $$f\in \mathcal {B},$$

f
∈
B
,

a solution of the problem of invariance of the above functional symmetries with respect to some one- and two-argument function operations and two applications of the mentioned function decomposition.
TRPM7 restrains plasmin activity and promotes transforming growth factor-β1 signaling in primary human lung fibroblasts
Authors: Zeitlmayr Sarah , Zierler Susanna , Staab-Weijnitz Claudia A. , Dietrich Alexander , Geiger Fabienne , Horgen F. David , Gudermann Thomas , Breit Andreas
Published: July 2022

Sustained exposure of the lung to various environmental or occupational toxins may eventually lead to pulmonary fibrosis, a devastating disease with no cure. Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix (ECM) proteins such as fibronectin and collagens. The peptidase plasmin degrades the ECM, but protein levels of the plasmin activator inhibitor-1 (PAI-1) are increased in fibrotic lung tissue, thereby dampening plasmin activity. Transforming growth factor-β1 (TGF-β1)-induced activation of SMAD transcription factors promotes ECM deposition by enhancing collagen, fibronectin and PAI-1 levels in pulmonary fibroblasts. Hence, counteracting TGF-β1-induced signaling is a promising approach for the therapy of pulmonary fibrosis. Transient receptor potential cation channel subfamily M Member 7 (TRPM7) supports TGF-β1-promoted SMAD signaling in T-lymphocytes and the progression of fibrosis in kidney and heart. Thus, we investigated possible effects of TRPM7 on plasmin activity, ECM levels and TGF-β1 signaling in primary human pulmonary fibroblasts (pHPF). We found that two structurally unrelated TRPM7 blockers enhanced plasmin activity and reduced fibronectin or PAI-1 protein levels in pHPF under basal conditions. Further, TRPM7 blockade strongly inhibited fibronectin and collagen deposition induced by sustained TGF-β1 stimulation. In line with these data, inhibition of TRPM7 activity diminished TGF-β1-triggered phosphorylation of SMAD-2, SMAD-3/4-dependent reporter activation and PAI-1 mRNA levels. Overall, we uncover TRPM7 as a novel supporter of TGF-β1 signaling in pHPF and propose TRPM7 blockers as new candidates to control excessive ECM levels under pathophysiological conditions conducive to pulmonary fibrosis.
Health‐Related Quality of Life After Breast Reconstruction: Comparing Outcomes Between Reconstruction Techniques Using the BREAST‐Q
Authors: Kuhlefelt Charlotta , Homsy Pauliina , Repo Jussi P. , Jahkola Tiina , Kauhanen Susanna
Published: July 2022

Background

Reconstruction of the breast following mastectomy can improve patients’ health‐related quality of life (HRQL). We aimed to assess HRQL in women after mastectomy and breast reconstruction and to identify differences in HRQL related to the reconstruction method used.

Methods

A cross‐sectional study was performed on patients who had undergone breast reconstruction in Helsinki University Hospital between 08/2017 and 7/2019. The postoperative HRQL was assessed using the BREAST‐Q (2.0) Reconstruction Module. The results were compared between patients with different reconstruction methods using the Kruskal–Wallis test.

Results

A total of 146 patients were identified. Microvascular flaps (n = 77) were the most common method for primary breast reconstruction, followed by latissimus dorsi (LD) flaps (n = 45), fat grafting (n = 18) and implant reconstruction (n = 6). The satisfaction with breasts was high in all groups (median 61, IQR 49–71). The physical well‐being of the chest was high regardless of the reconstructive method (median 100, IQR 80–100). However, women with fat grafting reported more adverse effects of radiation (median 17, IQR 14–17 vs. 18, IQR 17–18 for other groups, p = 0.02). Donor site morbidity was low, and patients reported high satisfaction with the back (median 66/100, IQR57‐90) and abdomen (median 9/12, IQR 8–10), and physical well‐being of the back (median 61/100, IQR 53–70) and abdomen (median 65/100, IQR 60–86).

Conclusions

The patient‐reported HRQL after breast reconstruction is high. Most women report being satisfied with the reconstruction, irrespective of the reconstruction method used. The reconstruction method can thus be chosen individually in cooperation between the patient and the surgeon.
The first patient-reported outcomes from the Utrecht Prostate Cohort (UPC): the first platform facilitating ‘trials within cohorts’ (TwiCs) for the evaluation of interventions for prostate cancer
Authors: Teunissen Frederik R. , Willigenburg Thomas , Meijer Richard P. , van Melick Harm H. E. , Verkooijen Helena M. , van der Voort van Zyp Jochem R. N.
Published: July 2022

Purpose

To describe the development and first outcomes of the Utrecht Prostate Cohort (UPC): the first ‘trials within cohorts’ (TwiCs) platform for prostate cancer (PCa).

Methods

All non-metastasized, histologically proven PCa patients who are planned to receive standard of care are eligible for inclusion in UPC. Patients provide informed consent for the collection of clinical and technical patient data, physician-reported outcomes, and patient-reported outcomes (PROs) up to 10 years post-treatment. Additionally, patients may provide broad consent for future randomization for experimental-intervention trials (TwiCs). Changes in PROs (EPIC-26 questionnaire domains) of the participants who received standard of care were analyzed using Wilcoxon signed-rank tests.

Results

In two years, 626 patients were enrolled, 503 (80.4%) of whom provided broad consent for future randomization. Among these, 293 (46.8%) patients underwent magnetic resonance-guided adaptive radiotherapy (MRgRT), 116 (18.5%) CT-guided external beam radiation therapy (EBRT), 109 (17.4%) robot-assisted radical prostatectomy (RARP), and 65 (10.4%) patients opted for active surveillance. Patients treated with MRgRT and CT-guided EBRT showed a transient but significant decline in urinary irritative/obstructive and bowel domain scores at 1-month follow-up. RARP patients showed a significant deterioration of urinary incontinence domain scores between baseline and all follow-up moments and significant improvement of urinary irritative/obstructive domain scores between baseline and 9- and 12-month follow-up. All radical treatment groups showed a significant decline in sexual domain scores during follow-up. Active surveillance patients showed no significant deterioration over time in all domains.

Conclusion

The first results from the UPC study show distinct differences in PROs between treatment options for PCa.

Registration No.: NCT04228211.
Acute corticospinal tract diffusion tensor imaging predicts 6-month functional outcome after intracerebral haemorrhage
Authors: Schwarz G. , Kanber B. , Prados F. , Browning S. , Simister R. , Jäger R. , Ambler G. , Wheeler-Kingshott C. A. M. Gandini , Werring David J.
Published: July 2022

Introduction

Diffusion tensor imaging (DTI) can assess the structural integrity of the corticospinal tract (CST) in vivo. We aimed to investigate whether CST DTI metrics after intracerebral haemorrhage (ICH) are associated with 6-month functional outcome and can improve the predictive performance of the existing ICH score.

Methods

We retrospectively included 42 patients with DTI performed within 5 days after deep supratentorial spontaneous ICH. Ipsilesional-to-contralesional ratios were calculated for fractional anisotropy (rFA) and mean diffusivity (rMD) in the pontine segment (PS) of the CST. We determined the most predictive variables for poor 6-month functional outcome [modified Rankin Scale (mRS) > 2] using the least absolute shrinkage and selection operator (LASSO) method. We calculated discrimination using optimism-adjusted estimation of the area under the curve (AUC).

Results

Patients with 6-month mRS > 2 had lower rFA (0.945 [± 0.139] vs 1.045 [± 0.130]; OR 0.004 [95% CI 0.00–0.77]; p =  0.04) and higher rMD (1.233 [± 0.418] vs 0.963 [± 0.211]; OR 22.5 [95% CI 1.46–519.68]; p = 0.02). Discrimination (AUC) values were: 0.76 (95% CI 0.61–0.91) for the ICH score, 0.71 (95% CI 0.54–0.89) for rFA, and 0.72 (95% CI 0.61–0.91) for rMD. Combined models with DTI and non-DTI variables offer an improvement in discrimination: for the best model, the AUC was 0.82 ([95% CI 0.68–0.95]; p = 0.15).

Conclusion

In our exploratory study, PS-CST rFA and rMD had comparable predictive ability to the ICH score for 6-month functional outcome. Adding DTI metrics to clinical-radiological scores might improve discrimination, but this needs to be investigated in larger studies.
Parkinson’s disease multimodal complex treatment improves gait performance: an exploratory wearable digital device-supported study
Authors: Scherbaum Raphael , Moewius Andreas , Oppermann Judith , Geritz Johanna , Hansen Clint , Gold Ralf , Maetzler Walter , Tönges Lars
Published: July 2022

Background

Wearable device-based parameters (DBP) objectively describe gait and balance impairment in Parkinson’s disease (PD). We sought to investigate correlations between DBP of gait and balance and clinical scores, their respective changes throughout the inpatient multidisciplinary Parkinson’s Disease Multimodal Complex Treatment (PD-MCT), and correlations between their changes.

Methods

This exploratory observational study assessed 10 DBP and clinical scores at the start (T1) and end (T2) of a two-week PD-MCT of 25 PD in patients (mean age: 66.9 years, median HY stage: 2.5). Subjects performed four straight walking tasks under single- and dual-task conditions, and four balance tasks.

Results

At T1, reduced gait velocity and larger sway area correlated with motor severity. Shorter strides during motor-motor dual-tasking correlated with motor complications. From T1 to T2, gait velocity improved, especially under dual-task conditions, stride length increased for motor-motor dual-tasking, and clinical scores measuring motor severity, balance, dexterity, executive functions, and motor complications changed favorably. Other gait parameters did not change significantly. Changes in motor complications, motor severity, and fear of falling correlated with changes in stride length, sway area, and measures of gait stability, respectively.

Conclusion

DBP of gait and balance reflect clinical scores, e.g., those of motor severity. PD-MCT significantly improves gait velocity and stride length and favorably affects additional DBP. Motor complications and fear of falling are factors that may influence the response to PD-MCT. A DBP-based assessment on admission to PD inpatient treatment could allow for more individualized therapy that can improve outcomes.

Trial registration number and date

DRKS00020948 number, 30-Mar-2020, retrospectively registered.
Subthalamic deep brain stimulation for refractory Gilles de la Tourette’s syndrome: clinical outcome and functional connectivity
Authors: Dai Lulin , Xu Wenying , Song Yunhai , Huang Peng , Li Ningfei , Hollunder Barbara , Horn Andreas , Wu Yiwen , Zhang Chencheng , Sun Bomin , Li Dianyou
Published: July 2022

Background

Deep brain stimulation (DBS) is a promising novel approach for managing refractory Gilles de la Tourette’s syndrome (GTS). The subthalamic nucleus (STN) is the most common DBS target for treating movement disorders, and smaller case studies have reported the efficacy of bilateral STN-DBS treatment for relieving tic symptoms. However, management of GTS and treatment mechanism of STN-DBS in GTS remain to be elucidated.

Methods

Ten patients undergoing STN-DBS were included. Tics severity was evaluated using the Yale Global Tic Severity Scale. The severities of comorbid psychiatric symptoms of obsessive–compulsive behavior (OCB), attention-deficit/hyperactivity disorder, anxiety, and depression; social and occupational functioning; and quality of life were assessed. Volumes of tissue activated were used as seed points for functional connectivity analysis performed using a control dataset.

Results

The overall tics severity significantly reduced, with 62.9% ± 26.2% and 58.8% ± 27.2% improvements at the 6- and 12-months follow-up, respectively. All three patients with comorbid OCB showed improvement in their OCB symptoms at both the follow-ups. STN-DBS treatment was reasonably well tolerated by the patients with GTS. The most commonly reported side effect was light dysarthria. The stimulation effect of STN-DBS might regulate these symptoms through functional connectivity with the thalamus, pallidum, substantia nigra pars reticulata, putamen, insula, and anterior cingulate cortices.

Conclusions

STN-DBS was associated with symptomatic improvement in severe and refractory GTS without significant adverse events. The STN is a promising DBS target by stimulating both sensorimotor and limbic subregions, and specific brain area doses affect treatment outcomes.
Prevalence of intronic repeat expansions in RFC1 in Dutch patients with CANVAS and adult-onset ataxia
Authors: Ghorbani Fatemeh , de Boer-Bergsma Jelkje , Verschuuren-Bemelmans Corien C. , Pennings Maartje , de Boer Eddy N. , Kremer Berry , Vanhoutte Els K. , de Vries Jeroen J. , van de Berg Raymond , Kamsteeg Erik-Jan , van Diemen Cleo C. , Westers Helga , van de Warrenburg Bart P. , Verbeek Dineke S.
Published: July 2022

Recently, an intronic biallelic (AAGGG)n repeat expansion in RFC1 was shown to be a cause of CANVAS and adult-onset ataxia in multiple populations. As the prevalence of the RFC1 repeat expansion in Dutch cases was unknown, we retrospectively tested 9 putative CANVAS cases and two independent cohorts (A and B) of 395 and 222 adult-onset ataxia cases, respectively, using the previously published protocol and, for the first time optical genome mapping to determine the size of the expanded RFC1 repeat. We identified the biallelic (AAGGG)n repeat expansion in 5/9 (55%) putative CANVAS patients and in 10/617 (1.6%; cohorts A + B) adult-onset ataxia patients. In addition to the AAGGG repeat motif, we observed a putative GAAGG repeat motif in the repeat expansion with unknown significance in two adult-onset ataxia patients. All the expanded (AAGGG)n repeats identified were in the range of 800–1299 repeat units. The intronic biallelic RFC1 repeat expansion thus explains a number of the Dutch adult-onset ataxia cases that display the main clinical features of CANVAS, and particularly when ataxia is combined with neuropathy. The yield of screening for RFC1 expansions in unselected cohorts is relatively low. To increase the current diagnostic yield in ataxia patients, we suggest adding RFC1 screening to the genetic diagnostic workflow by using advanced techniques that attain long fragments.
Training deep material networks to reproduce creep loading of short fiber-reinforced thermoplastics with an inelastically-informed strategy
Authors: Dey Argha Protim , Welschinger Fabian , Schneider Matti , Gajek Sebastian , Böhlke Thomas
Published: July 2022

Deep material networks (DMNs) are a recent multiscale technology which enable running concurrent multiscale simulations on industrial scale with the help of powerful surrogate models for the micromechanical problem. Classically, the parameters of the DMNs are identified based on linear elastic precomputations. Once the parameters are identified, DMNs may process inelastic material models and were shown to reproduce micromechanical full-field simulations with the original microstructure to high accuracy. The work at hand was motivated by creep loading of thermoplastic components with fiber reinforcement. In this context, multiple scales appear, both in space (due to the reinforcements) and in time (short- and long-term effects). We demonstrate by computational examples that the classical training strategy based on linear elastic precomputations is not guaranteed to produce DMNs whose long-term creep response accurately matches high-fidelity computations. As a remedy, we propose an inelastically informed early stopping strategy for the offline training of the DMNs. Moreover, we introduce a novel strategy based on a surrogate material model, which shares the principal nonlinear effects with the true model but is significantly less expensive to evaluate. For the problem at hand, this strategy enables saving significant time during the parameter identification process. We demonstrate that the novel strategy provides DMNs which reliably generalize to creep loading.
Dynamics of cardiovascular and baroreflex readjustments during a light-to-moderate exercise transient in humans
Authors: Taboni Anna , Fagoni Nazzareno , Fontolliet Timothée , Vinetti Giovanni , Ferretti Guido
Published: July 2022

Purpose

We hypothesised that, during a light-to-moderate exercise transient, compared to an equivalent rest-to-exercise transient, (1) a further baroreflex sensitivity (BRS) decrease would be slower, (2) no rapid heart rate (HR) response would occur, and (3) the rapid cardiac output (CO) response would have a smaller amplitude (A1). Hence, we analysed the dynamics of arterial baroreflexes and the HR and CO kinetics during rest-to-50 W (0–50 W) and 50-to-100 W (50–100 W) exercise transients.

Methods

10 subjects performed three 0–50 W and three 50–100 W on a cycle ergometer. We recorded arterial blood pressure profiles (photo-plethysmography) and R-to-R interval (RRi, electrocardiography). The former were analysed to obtain beat-by-beat mean arterial pressure (MAP) and stroke volume (SV). CO was calculated as SV times HR. BRS was measured by modified sequence method.

Results

During 0–50 W, MAP transiently fell (− 9.0 ± 5.7 mmHg, p < 0.01) and BRS passed from 15.0 ± 3.7 at rest to 7.3 ± 2.4 ms mmHg−1 at 50 W (p < 0.01) promptly (first BRS sequence: 8.1 ± 4.6 ms mmHg−1, p < 0.01 vs. rest). During 50–100 W, MAP did not fall and BRS passed from 7.2 ± 2.6 at 50 W to 3.3 ± 1.3 ms mmHg−1 at 100 W (p < 0.01) slowly (first BRS sequence: 5.3 ± 3.1 ms mmHg−1, p = 0.07 vs. 50 W). A1 for HR was 9.2 ± 6.0 and 6.0 ± 4.5 min−1 in 0–50 W and 50–100 W, respectively (p = 0.19). The corresponding A1 for CO were 2.80 ± 1.54 and 0.91 ± 0.55 l∙min−1 (p < 0.01).

Conclusion

During 50–100 W, with respect to 0–50 W, BRS decreased more slowly, in absence of a prompt pressure decrease. BRS decrease and rapid HR response in 50–100 W were unexpected and ascribed to possible persistence of some vagal tone at 50 W.
COVID-19 in children and adolescents: MIS(-C)-taken diagnoses
Authors: van der Steen M. , Leroy P. L. , Driessen G. J. A. , Bannier M. A. G. E.
Published: July 2022

Multisystem inflammatory syndrome in children (MIS-C) is an inflammatory condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is characterized by fever, gastro-intestinal symptoms, cardiovascular complications, conjunctivitis, skin involvement, elevated inflammatory markers, and coagulation abnormalities. The current ongoing COVID-19 pandemic causes an increased alertness to MIS-C. In combination with the heterogeneous clinical spectrum, this could potentially lead to diagnostic blindness, misdiagnosis of MIS-C, and overtreatment with expensive IVIG treatment. This report demonstrates the challenge of accurately distinguishing MIS-C from other more common inflammatory pediatric diseases, and the need to act with caution to avoid misdiagnoses in the current pandemic. We present a case series of 11 patients suspected of MIS-C based on the current definitions. Three of them were eventually diagnosed with a different disease.

Conclusion: Current definitions and diagnostic criteria lack specificity which potentially leads to misdiagnosis and overtreatment of MIS-C. We emphasize the need to act with caution in order to avoid MIS(-C)-taken diagnoses in the current pandemic.What is Known:• A pediatric multisystem inflammatory disease associated with SARS-CoV-2 has been described (MIS-C).• There are three definitions being used for MIS-C, all including fever for at least 24 h, laboratory evidence of inflammation, clinically severe illness with multi-organ (≥ 2) involvement, and no alternative plausible diagnosis.What is New:• MIS-C has a heterogeneous clinical spectrum without distinctive features compared to more common childhood diseases. Current definitions and diagnostic criteria for MIS-C lack specificity which leads to misdiagnosis and overtreatment.• Amid the current excessive attention to COVID-19 and MIS-C, pediatricians should remain vigilant to avoid mistaken diagnoses.
Schmerzmittelgebrauch in Deutschland
Authors: Diener Hans-Christoph , Lehmacher Walter , Kroth Elmar , Lampert Anette , Weiser Thomas
Published: July 2022

Hintergrund

Publizierte Daten zum Pro-Kopf-Gebrauch von Schmerzmitteln in Deutschland liegen nur bis zum Jahr 2005 vor. In der vorliegenden Analyse wurden Daten für die Jahre 2008 bis 2019 ausgewertet. Es wurde der Gebrauch von rezeptpflichtigen wie rezeptfreien Analgetika untersucht, mögliche Einflussgrößen wurden diskutiert.

Methodik

Der Pro-Kopf-Gebrauch von verschreibungspflichtigen und rezeptfreien Analgetika wurde auf Basis von verlässlichen Daten zu Rezepten und Bareinkäufen in Apotheken ermittelt (IMS Pharmascope®). Für rezeptfreie Präparate wurde zudem eine Auswertung nach Wirkstoffen vorgenommen. Zusätzlich wurden Werbeaufwendungen pharmazeutischer Hersteller und Veränderungen der Abgabewege als mögliche Einflussgrößen analysiert.

Ergebnisse

Innerhalb des Beobachtungszeitraums ist der Gebrauch von verschreibungspflichtigen Analgetika angestiegen, während der Gebrauch von rezeptfreien Analgetika gesunken ist. Monopräparate machen den Großteil des Absatzes von rezeptfreien Schmerzmitteln aus. Der Anteil von Kombinationspräparaten war in den letzten Jahren rückläufig.

Diskussion

Der Gebrauch von rezeptfreien Analgetika in Deutschland war zwischen 2008 und 2019 rückläufig. Damit setzt sich der Trend ab 1995, der in einer vorherigen Untersuchung beobachtet wurde, fort. Externe Faktoren wie der Anstieg von Werbeausgaben oder der leichtere Zugang über Versandapotheken scheinen den Gebrauch nicht zu beeinflussen.
Land–sea thermal contrast associated with summer monsoon onset over the Chao Phraya River basin
Authors: Yamada Tomohito J. , Shrivastava Sourabh , Kato Ryosuke
Published: July 2022

Earlier onset of the Southeast Asian summer monsoon (SAM) was observed over the Chao Phraya River basin in Thailand using Thai Meteorological Department-derived high-resolution merged rainfall data from 1981 to 2016. SAM variability depends on numerous local and global factors, including thermal conditions over the Bay of Bengal (BoB) and Tibetan Plateau (TbT). Despite tremendous past research efforts, the effect of thermal heat contrast on the SAM remains unclear. Using observational and reanalysis datasets, we found that the absolute value of total heat over the BoB was increasing. However, the interannual variability of total heat was greater over the TbT. Changes in surface temperature (± 1.5 °C), air thickness (± 20 m), and geopotential height over the TbT were associated with the timing of SAM onset. The results also suggested that significant changes in air thickness are driven by surface temperature differences over the TbT, while changes in the integrated apparent heat source and integrated apparent moisture sink of ± 100 W m−2 resulted in anomalous convective activities over the BoB and mainland of the Indochina Peninsula in years of early and late SAM onset. At the intraseasonal timescale, Madden–Julian oscillation (MJO) was observed over the Indian Ocean and Western Hemisphere for 4–10 days in years of early SAM onset. The opposite situation was found for years of late SAM onset, with MJO located over the Western Pacific Ocean and Maritime Continent.
The persistent effects of foetal growth on child and adolescent mental health: longitudinal evidence from a large population-based cohort
Authors: Dooley Niamh , Healy Colm , Cotter David , Clarke Mary , Cannon Mary
Published: July 2022

Low birth weight for one’s gestational age is associated with higher rates of child psychopathology, however, most studies assess psychopathology cross-sectionally. The effect of such foetal growth restriction appears to be strongest for attention problems in childhood, although adult studies have found associations with a range of outcomes, from depression to psychosis. We explore how associations between foetal growth and psychopathology change across age, and whether they vary by sex. We used a large nationally representative cohort of children from Ireland (N ~ 8000). Parents completed the Strengths and Difficulties Questionnaire (SDQ) at 3 time points (age 9, 13 and 17). Outcomes included a total problems scale and subscales measuring attention/hyperactivity, peer, conduct and emotional problems. Foetal growth had significant associations with all problem scales, even after controlling for sex, socioeconomic factors and parental mental health. The magnitude of these effects was small but relatively stable across ages 9–17. In males, foetal growth had the strongest associations with attention/hyperactivity and peer problems, whereas females showed more widespread associations with all four subscales. There was a trend for the association between foetal growth and emotional problems to increase with advancing age, approaching the borderline-abnormal threshold by age 17. Reduced foetal growth predicted persistently higher scores on all measured aspects of child and adolescent psychopathology. Associations with child attention/hyperactivity may generalize to a wider array of adult psychopathologies via adolescent-onset emotional problems. Future studies should explore potential age-dependent effects of foetal growth into the early 20s.
Emotional and socio-cognitive processing in young children with symptoms of anxiety
Authors: Howe-Davies Holly , Hobson Christopher , Waters Cerith , van Goozen Stephanie H. M.
Published: July 2022

Many children with anxiety disorders exhibit significant and persistent impairments in their social and interpersonal functioning. Two components essential for successful social interaction are empathy and theory of mind (ToM). Both constructs develop rapidly in childhood, but no study has simultaneously examined these skills in young children with emerging mental health problems, including those with symptoms of anxiety. This study investigated empathy and ToM in children with anxiety symptomatology and examined their relationship with anxiety severity. A cross-sectional study was carried out with 174 children aged 4–8 years with emerging mental health difficulties who were referred by school teachers for an assessment because of emotional, cognitive, or behavioural problems at school. Participants completed empathy and ToM tasks. Parents were interviewed and rated children’s emotional and behavioural problems. Correlational analyses indicated that elevated anxiety was associated with better cognitive ToM and worse affective empathy; there were no associations between anxiety and either cognitive empathy or affective ToM. Subsequent regression analyses demonstrated that whilst enhanced cognitive ToM was explained by age and verbal IQ, anxiety symptoms uniquely predicted impaired affective empathy. These results indicate that children with symptoms of anxiety have difficulty in sharing in other people’s emotions. As a result, they may find it difficult to behave in socially adequate ways in interactions with others that involve affective sharing. These findings encourage the use of early and targeted interventions that improve affective empathy development in children with anxiety symptoms.
Rocking the Boat: Loot Boxes in Online Digital Games, the Regulatory Challenge, and the EU’s Unfair Commercial Practices Directive
Authors: Leahy D.
Published: July 2022

The loot box, a feature of online video games, contains randomised virtual items of importance to gameplay. Comparisons are drawn between chance-based loot boxes and the legal and psychological definitions of gambling, leading to concerns that the format may be an unregulated form of quasi-gambling. Globally, several jurisdictions have intervened to control the loot box, some applying national gambling laws, while others have implemented more general rules, an alternative described as “consumer protection”. In 2020, a study commissioned on behalf of the EU Parliament recommended that loot boxes and in-game purchasing systems be regulated from a “consumer protection” perspective. This paper questions firstly whether the debate on product-specific rules for loot box games was conducted in reverse, commencing with a set of potential solutions, while research on harms is still at an early stage. It interrogates the “consumer protection” route, critiquing proposals that borrow from the conceptually and structurally distinct areas of gambling law and consumer protection law, without first resolving the tensions between them. The paper proposes that an alternative paradigm of “player protection” may be the better route towards solving the regulatory puzzle of loot boxes. The paper secondly argues for the EU and its Member States to adopt an interim approach, relying on existing legislation to tackle immediate concerns and facilitate testing of remedial measures, but which leaves the door ajar to alternative options, including regulation under national gambling law frameworks. It examines the UCPD as an immediate solution and considers how the updated UCPD Guidance addresses questions of potentially exploitative game design.
Coal tailings as a soil conditioner: evaluation of tailing properties and effect on tomato plants
Authors: Yong Miing-Tiem , Babla Mohammad , Karan Shawan , Katwal Utsab , Jahandari Soheil , Matta Pushpinder , Chen Zhong-Hua , Tao Zhong
Published: July 2022

The global coal industry yields a vast amount of tailings waste, and the utilisation of these tailings necessitates innovative efforts contributing to the United Nations Sustainable Development Goals. One of such novel initiatives is to reuse coal tailings (CT) safely, ecofriendly, and cost-effectively in agroecosystems as a soil conditioner to enhance the productivity of lands. This study aimed to evaluate the potential utilisation of coal tailings waste in the soil amelioration to improve plant performance. The physico–chemical characteristics of coal tailings from two Australian mining sites (CT1 and CT2) showed that the tailings samples are alkaline with loamy and loamy sand textures, respectively. The tailings have ~ 3% of macronutrients, high carbon (C), and low heavy metals and metalloids (As, Cd, Se, Cu, Zn, and Pb). The germination rate of tomato seeds was improved in the low-rate CT treatment. Greenhouse tomato plants exhibited an increase in leaf’s K, Ca, and Mg contents in CT1 and CT2 treatments. More importantly, the CT treatment-induced accumulation of heavy metals in plants was mostly insignificant in both CT treatments. Therefore, we highlight the potential application of coal tailings as a soil conditioner because of the beneficial effect of improved carbon and nutrients (N, P, K, Mg, and Ca) in tomato leaves. Further amendment of the coal tailings should focus on the adjustment of pH and the addition of other beneficial materials for the improvement of soil properties for crops in both the greenhouse and the field.
A High-Order Residual-Based Viscosity Finite Element Method for the Ideal MHD Equations
Authors: Dao Tuan Anh , Nazarov Murtazo
Published: July 2022

We present a high order, robust, and stable shock-capturing technique for finite element approximations of ideal MHD. The method uses continuous Lagrange polynomials in space and explicit Runge-Kutta schemes in time. The shock-capturing term is based on the residual of MHD which tracks the shock and discontinuity positions, and adds sufficient amount of viscosity to stabilize them. The method is tested up to third order polynomial spaces and an expected fourth-order convergence rate is obtained for smooth problems. Several discontinuous benchmarks such as Orszag-Tang, MHD rotor, Brio-Wu problems are solved in one, two, and three spacial dimensions. Sharp shocks and discontinuity resolutions are obtained.
Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis
Authors: Luger Anna-Luisa , König Sven , Samp Patrick Felix , Urban Hans , Divé Iris , Burger Michael C. , Voss Martin , Franz Kea , Fokas Emmanouil , Filipski Katharina , Demes Melanie-Christin , Stenzinger Albrecht , Sahm Felix , Reuss David E. , Harter Patrick N. , Wagner Sebastian , Hattingen Elke , Wichert Jennifer , Lapa Constantin , Fröhling Stefan , Steinbach Joachim P. , Ronellenfitsch Michael W.
Published: July 2022

Purpose

Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed to evaluate the decision-making process of molecular targeted therapies and analyze data on tolerability as well as signals for efficacy.

Methods

Via retrospective analysis, we identified primary brain tumor patients who were treated off-label with a targeted therapy at the University Hospital Frankfurt, Goethe University. We analyzed which types of molecular alterations were utilized to guide molecular off-label therapies and the diagnostic procedures for their assessment during the period from 2008 to 2021. Data on tolerability and outcomes were collected.

Results

413 off-label therapies were identified with an increasing annual number for the interval after 2016. 37 interventions (9%) were targeted therapies based on molecular markers. Glioma and meningioma were the most frequent entities treated with molecular matched targeted therapies. Rare entities comprised e.g. medulloblastoma and papillary craniopharyngeoma. Molecular targeted approaches included checkpoint inhibitors, inhibitors of mTOR, FGFR, ALK, MET, ROS1, PIK3CA, CDK4/6, BRAF/MEK and PARP. Responses in the first follow-up MRI were partial response (13.5%), stable disease (29.7%) and progressive disease (46.0%). There were no new safety signals. Adverse events with fatal outcome (CTCAE grade 5) were not observed. Only, two patients discontinued treatment due to side effects. Median progression-free and overall survival were 9.1/18 months in patients with at least stable disease, and 1.8/3.6 months in those with progressive disease at the first follow-up MRI.

Conclusion

A broad range of actionable alterations was targeted with available molecular therapeutics.

However, efficacy was largely observed in entities with paradigmatic oncogenic drivers, in particular with BRAF mutations. Further research on biomarker-informed molecular matched therapies is urgently necessary.
User engagement with scholarly tweets of scientific papers: a large-scale and cross-disciplinary analysis
Authors: Fang Zhichao , Costas Rodrigo , Wouters Paul
Published: July 2022

This study investigates the extent to which scholarly tweets of scientific papers are engaged with by Twitter users through four types of user engagement behaviors, i.e., liking, retweeting, quoting, and replying. Based on a sample consisting of 7 million scholarly tweets of Web of Science papers, our results show that likes is the most prevalent engagement metric, covering 44% of scholarly tweets, followed by retweets (36%), whereas quotes and replies are only present for 9% and 7% of all scholarly tweets, respectively. From a disciplinary point of view, scholarly tweets in the field of Social Sciences and Humanities are more likely to trigger user engagement over other subject fields. The presence of user engagement is more associated with other Twitter-based factors (e.g., number of mentioned users in tweets and number of followers of users) than with science-based factors (e.g., citations and Mendeley readers of tweeted papers). Building on these findings, this study sheds light on the possibility to apply user engagement metrics in measuring deeper levels of Twitter reception of scholarly information.
IoT framework for brain tumor detection based on optimized modified ResNet 18 (OMRES)
Authors: El-Feshawy Somaya A. , Saad Waleed , Shokair Mona , Dessouky Moawad
Published: July 2022

Brain tumors are a serious health issue that affects many people’s lives. Such a tumor, which is either benign or malignant, can be fatal if malignant cells are not correctly diagnosed. According to the most recent human health care analysis system, the number of brain tumor patients has climbed dramatically and is now the 10th top cause of death. As a result, detecting brain tumors in their early stages can considerably improve the patient’s prospects of complete recovery and therapy. Thanks to improvements in information and communication technology, the Internet of things (IoT) has reached an evolutionary stage in the development of the modern health care environment. This paper provides a detailed examination of brain tumor detection approaches. Moreover, two different scenarios for detecting brain tumors will be proposed. On one hand, the first scenario depends on applying a deep convolutional neural network directly to brain images. On the other hand, the second scenario presents an IoT-based framework that adopts a multiuser detection system by sending the images to the cloud for early detection of brain tumors, which makes the system accessible to anyone and anywhere for accurate brain tumor categorization. The proposed CNN structure can be considered a modified version of the pre-trained ResNet18 CNN. Additionally, two key hyper-parameters are used to fine-tune the OMRES model, firstly different optimizers are tested using different learning rates, batch sizes, and a constant number of epochs, and secondly, the impact of changing dropout rates is made. Finally, comparisons between the OMRES model and traditional pre-trained models are discussed. Based on simulation findings, the RMSProp algorithm with a dropout rate of 0.5 verifies the best outcomes over other algorithms, where the suggested model achieves superior improvement with the highest rated accuracy of 98.67% compared to the conventional CNNs.
Early Stopping Criterion for Recursive Least Squares Training of Behavioural Models
Authors: Loughman Méabh , Barton Sinéad , Farrell Ronan , Dooley John
Published: July 2022

The necessity of the rapid evolution of wireless communications, with continuously increasing demands for higher data rates and capacity Zheng (Big datadriven optimization for mobile networks toward 5g 30:44–51, 2016), is constantly augmenting the complexity of radio frequency (RF) transceiver architecture. A significant component in the configuration of such complex radio transceivers is the power amplifier(PA). Multiple distributed PAs are now common in proposed RF architectures. PAs exhibit non linear behaviour, causing signal distortion in transmission. Behavioural models offer a concise representation of a PAs characteristic performance which is extremely useful in simulating performance of multiple nonlinear power amplifiers. A considerable drawback with using the Recursive Least Squares (RLS) technique is that the instability of the coefficients during the training of the model. This manuscript provides a computationally efficient technique to detect the onset of instability during adaptive RLS training and subsequently to inform the decision to cease training of dynamic memory polynomial based behavioural models, to avoid the onset of instability. The proposed technique does not require modification of the RLS algorithm, merely an observation of the pre-exsisting autocorrelation function based update. This technique is experimentally validated using four different signal modulation schemes, LTE OFDM, 5G-NR, DVBS2X and WCDMA.
Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics
Authors: Kananen Laura , Hurme Mikko , Bürkle Alexander , Moreno-Villanueva Maria , Bernhardt Jürgen , Debacq-Chainiaux Florence , Grubeck-Loebenstein Beatrix , Malavolta Marco , Basso Andrea , Piacenza Francesco , Collino Sebastiano , Gonos Efstathios S. , Sikora Ewa , Gradinaru Daniela , Jansen Eugene H. J. M. , Dollé Martijn E. T. , Salmon Michel , Stuetz Wolfgang , Weber Daniela , Grune Tilman , Breusing Nicolle , Simm Andreas , Capri Miriam , Franceschi Claudio , Slagboom Eline , Talbot Duncan , Libert Claude , Raitanen Jani , Koskinen Seppo , Härkänen Tommi , Stenholm Sari , Ala-Korpela Mika , Lehtimäki Terho , Raitakari Olli T. , Ukkola Olavi , Kähönen Mika , Jylhä Marja , Jylhävä Juulia
Published: July 2022

Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.

cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.

In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.
Third Generation of Unary Calphad Descriptions and the Avoidance of Re-Stabilized Solid Phases and Unexpected Large Heat Capacity
Authors: Schmid-Fetzer Rainer
Published: July 2022

The problem of solid phase re-stabilization at high temperature in the latest version of 3rd generation data for pure solid elements is studied and the remedy to apply new Calphad software with the Equal-Entropy Criterion (EEC) implemented is critically examined. The concept of Equal-Entropy Temperature (EET) as very top limit for crystal existence is used to develop amendments by a second temperature range without introducing any adjustable parameter to an existing set of 3rd generation unary functions of solid and liquid. This is shown to safely prevent by definition of the mathematical Gibbs energy function the violation of the EEC axiom, namely that no solid phase should be more stable than the liquid at high temperature. The comprehensive amendment also solves the problem of unexpected large Cp contributions at high temperature. Detailed analyses are provided for the examples of pure Al and for binary Al-Ir, Al-Cr and Al-C systems. Serious risks of unforeseen pitfalls and artifacts are exemplified for some cases where an automatic exclusion of an stable phase by new “EEC-software” may occur. It is argued that this is not acceptable at least for applied Calphad simulations.
Frailty assessment in emergency medicine using the Clinical Frailty Scale: a scoping review
Authors: Fehlmann Christophe Alain , Nickel Christian Hans , Cino Emily , Al-Najjar Zinnia , Langlois Nigèle , Eagles Debra
Published: July 2022

Background

Frailty is a common condition present in older Emergency Department (ED) patients that is associated with poor health outcomes. The Clinical Frailty Scale (CFS) is a tool that measures frailty on a scale from 1 (very fit) to 9 (terminally ill). The goal of this scoping review was to describe current use of the CFS in emergency medicine and to identify gaps in research.

Methods

We performed a systemic literature search to identify original research that used the CFS in emergency medicine. Several databases were searched from January 2005 to July 2021. Two independent reviewers completed screening, full text review and data abstraction, with a focus on study characteristics, CFS assessment (evaluators, timing and purpose), study outcomes and statistical methods.

Results

A total of 4818 unique citations were identified; 34 studies were included in the final analysis. Among them, 76% were published after 2018, mainly in Europe or North America (79%). Only two assessed CFS in the pre-hospital setting. The nine-point scale was used in 74% of the studies, and patient consent was required in 69% of them. The main reason to use CFS was as a main exposure (44%), a potential predictor (15%) or an outcome (15%). The most frequently studied outcomes were mortality and hospital admission.

Conclusion

The use of CFS in emergency medicine research is drastically increasing. However, the reporting is not optimal and should be more standardized. Studies evaluating the impact of frailty assessment in the ED are needed.

Registration

https://doi.org/10.17605/OSF.IO/W2F8N