bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-time cognitive performance and positive symptom expression in schizophrenia
Authors: Dupuy Maud , Abdallah Majd , Swendsen Joel , N’Kaoua Bernard , Chanraud Sandra , Schweitzer Pierre , Fatseas Melina , Serre Fuschia , Barse Elodie , Auriacombe Marc , Misdrahi David
Published: July 2021

Deficits in cognitive functions are frequent in schizophrenia and are often conceptualized as stable characteristics of this disorder. However, cognitive capacities may fluctuate over the course of a day and it is unknown if such variation may be linked to the dynamic expression of psychotic symptoms. This investigation used Ecological Momentary Assessment (EMA) to provide mobile tests of cognitive functions and positive symptoms in real time. Thirty-three individuals with schizophrenia completed five EMA assessments per day for a one-week period that included real-time assessments of cognitive performance and psychotic symptoms. A subsample of patients and 31 healthy controls also completed a functional MRI examination. Relative to each individual’s average score, moments of worsened cognitive performance on the mobile tests were associated with an increased probability of positive symptom occurrence over subsequent hours of the day (coef = 0.06, p < 0.05), adjusting for the presence of psychotic symptoms at the moment of mobile test administration. These prospective associations varied as a function of graph theory indices in MRI analyses. These findings demonstrate that cognitive performance is prospectively linked to psychotic symptom expression in daily life, and that underlying brain markers may be observed in the Executive Control Network. While the potential causal nature of this association remains to be investigated, our results offer promising prospects for a better understanding of the underlying mechanisms of symptom expression in schizophrenia.
On the effect of the inlet configuration for anaerobic digester mixing
Authors: Dabiri Soroush , Sappl Johannes , Kumar Prashant , Meister Michael , Rauch Wolfgang
Published: July 2021

Sludge recirculation mixing in anaerobic digesters is essential for the stable operation of the digestion process. While often neglected, the configuration of the sludge inlet has a substantial influence on the efficiency of the mixing process. The fluid is either injected directly into the enclosed fluid domain or splashes onto the free surface of the slurry flow. In this paper, the aim was to investigate the effect of the inlet configuration by means of computational fluid dynamics—using ANSYS Fluent. Single-phase and multi-phase models are applied for a submerged and splashing inlet, respectively. To reduce the high computational demand, we also develop surrogate single-phase models for the splashing inlet. The digester mixing is analyzed by comparing velocity contours, velocity profiles, mixing time and dead volume. The non-Newtonian characteristics of the sludge is considered, and a $$k-\varepsilon $$

k
-
ε

model is employed for obtaining turbulence closure. Our method is validated by means of a previous study on the same geometry. Applying a submerged inlet configuration, the resulting dead volume in the tank is estimated around 80 times lower than for the case of a splashing inlet. Additionally, by emulating the multi-phase model for splashing inlet configurations with a single-phase one, the simulation clock time reduced to 15%.
Using human pose information for handgun detection
Authors: Velasco-Mata Alberto , Ruiz-Santaquiteria Jesus , Vallez Noelia , Deniz Oscar
Published: July 2021

Fast automatic handgun detection can be very useful to avoid or mitigate risks in public spaces. Detectors based on deep learning methods have been proposed in the literature to trigger an alarm if a handgun is detected in the image. However, those detectors are solely based on the weapon appearance on the image. In this work, we propose to combine the detector with the individual’s pose information in order to improve overall performance. To this end, a model that integrates grayscale images from the output of the handgun detector and heatmap-like images that represent pose is proposed. The results show an improvement over the original handgun detector. The proposed network provides a maximum improvement of a 17.5% in AP of the proposed combinational model over the baseline handgun detector.
Work absenteeism and disability associated with psoriasis and psoriatic arthritis in the USA—a retrospective study of claims data from 2009 TO 2020
Authors: Orbai A. M. , Reddy S. M. , Dennis N. , Villacorta R. , Peterson S. , Mesana L. , Chakravarty S. D. , Lin I. , Karyekar C. S. , Wang Y. , Pacou M. , Walsh J.
Published: July 2021

Objectives

To compare work absenteeism and short-term disability among adults with psoriasis or psoriatic arthritis (PsA), versus controls in the USA.

Methods

Adults eligible for work absenteeism and/or short-term disability benefits between 1/1/2009 and 4/30/2020 were screened in the IBM® MarketScan® Commercial and Health and Productivity Management Databases. The following groups were defined: (1) psoriasis: ≥ 2 psoriasis diagnoses ≥ 30 days apart and no PsA diagnoses; (2) PsA: ≥ 2 PsA diagnoses ≥ 30 days apart; (3) control: absence of psoriasis and PsA diagnoses. Controls were matched to psoriasis and PsA patients based on age, gender, index year, and comorbidities. Non-recreational work absences and sick leaves were evaluated in absentee-eligible patients, and short-term disability was evaluated in short-term disability-eligible patients. Costs (in 2019 USD) associated with each type of work absence were evaluated.

Results

4261 psoriasis and 616 PsA absentee-eligible and 25,213 psoriasis and 3480 PsA short-term disability-eligible patients were matched to controls. Average non-recreational work absence costs were $1681, $1657, and $1217 for the PsA, psoriasis, and control group, respectively. Compared with psoriasis patients and controls, more PsA patients had sick leaves after 1 year (56.2% versus 55.6% and 41.5%, p < 0.0001). Similarly, short-term disability was more frequent in PsA patients than psoriasis patients and controls at year one (8.8% versus 5.6% and 4.7%, p < 0.0001) and corresponding costs were higher ($605, $406, and $335 on average, p < 0.0001).

Conclusion

Annual work absenteeism and short-term disability were consistently greater among patients with PsA and psoriasis than controls, highlighting the substantial economic burden of psoriatic disease.

Key points• Patients with PsA had greater short-term disability compared with patients with psoriasis and patients with neither psoriasis nor PsA.• Patients with PsA and patients with psoriasis incurred greater non-recreational work absences and sick leaves than patients with neither psoriasis nor PsA.
Prognostic value of programmed death-ligand 1 status in Japanese patients with renal cell carcinoma
Authors: Uemura Motohide , Nakaigawa Noboru , Sassa Naoto , Tatsugami Katsunori , Harada Kenichi , Yamasaki Toshinari , Matsubara Nobuaki , Yoshimoto Takuya , Nakagawa Yuki , Fukuyama Tamaki , Oya Mototsugu , Shinohara Nobuo , Uemura Hirotsugu , Tsuzuki Toyonori
Published: July 2021

Background

Programmed death-ligand 1 (PD-L1) positivity is associated with poor prognosis in renal cell carcinoma (RCC). Because the prognostic impact and effect of confounding factors are less known, we investigated the prognostic significance of PD-L1 expression in Japanese patients with recurrent/metastatic RCC who started systemic therapy in 2010–2015.

Methods

This multicenter, retrospective study recruited patients from 29 Japanese study sites who had prior systemic therapy for RCC (November 2018 to April 2019) and stored formalin-fixed paraffin-embedded primary lesion samples. The primary outcome was overall survival (OS) by PD-L1 expression. Secondary outcomes included OS in subgroups and duration of first- and second-line therapies by PD-L1 expression. OS distributions were estimated using Kaplan–Meier methodology.

Results

PD-L1 expression (on immune cells [IC] ≥ 1%) was observed in 315/770 (40.9%) patients. PD-L1 positivity was more prevalent in patients with poor risk per both Memorial Sloan Kettering Cancer Center [MSKCC] and International Metastatic RCC Database Consortium, and high-risk pathological features (higher clinical stage, nuclear grade and sarcomatoid features). Median OS for PD-L1–positive patients was 30.9 months (95% CI 25.5–35.7) versus 37.5 months (95% CI 34.0–42.6) for PD-L1–negative patients (HR 1.04 [90% CI 0.89–1.22, p = 0.65]; stratified by MSKCC risk and liver metastases). Propensity score weight (PSW)-adjusted OS was similar between PD-L1–positive and –negative patients (median 34.4 versus 31.5 months; estimated PSW-adjusted HR 0.986).

Conclusions

This study suggests PD-L1 status was not an independent prognostic factor in recurrent/metastatic RCC during the study period because PD-L1 positivity was associated with poor prognostic factors, especially MSKCC risk status.
Increased gene expression variability in BRCA1-associated and basal-like breast tumours
Authors: Wiggins George A. R. , Black Michael A. , Dunbier Anita , Morley-Bunker Arthur E. ,   kConFab Investigators, Pearson John F. , Walker Logan C.
Published: July 2021

Purpose

Inherited variants in the cancer susceptibility genes, BRCA1 and BRCA2 account for up to 5% of breast cancers. Multiple gene expression studies have analysed gene expression patterns that maybe associated with BRCA12 pathogenic variant status; however, results from these studies lack consensus. These studies have focused on the differences in population means to identified genes associated with BRCA1/2-carriers with little consideration for gene expression variability, which is also under genetic control and is a feature of cellular function.

Methods

We measured differential gene expression variability in three of the largest familial breast cancer datasets and a 2116 breast cancer meta-cohort. Additionally, we used RNA in situ hybridisation to confirm expression variability of EN1 in an independent cohort of more than 500 breast tumours.

Results

BRCA1-associated breast tumours exhibited a 22.8% (95% CI 22.3–23.2) increase in transcriptome-wide gene expression variability compared to BRCAx tumours. Additionally, 40 genes were associated with BRCA1-related breast cancers that had ChIP-seq data suggestive of enriched EZH2 binding. Of these, two genes (EN1 and IGF2BP3) were significantly variable in both BRCA1-associated and basal-like breast tumours. RNA in situ analysis of EN1 supported a significant (p = 6.3 × 10−04) increase in expression variability in BRCA1-associated breast tumours.

Conclusion

Our novel results describe a state of increased gene expression variability in BRCA1-related and basal-like breast tumours. Furthermore, genes with increased variability may be driven by changes in DNA occupancy of epigenetic effectors. The variation in gene expression is replicable and led to the identification of novel associations between genes and disease phenotypes.
Is it ‘cancer prevention’ or ‘risk reduction’? #Wordsmatter
Authors: Walker Desiree A. H. , Terry Mary Beth
Published: July 2021

In this commentary, we examine whether we should reconsider the widespread use of the words ‘cancer prevention’ and replace them with the words ‘cancer risk reduction’. Our recommendation is because ‘risk reduction’ more accurately reflects what we know from cancer research, but more importantly recognizes the confusion and potential harm to patients from the inaccurate use of the words ‘cancer prevention’.
Exposure radius of a local coal mine in an Arctic coastal system; correlation between PAHs and mercury as a marker for a local mercury source
Authors: Steenhuisen Frits , van den Heuvel-Greve Martine
Published: July 2021

Mercury in the Arctic originates from emissions and releases at lower latitudes and, to a lesser extent, from local and regional sources. The relationship between mercury (Hg) and polycyclic aromatic hydrocarbons (PAHs) in sediment can be applied as an indicator of the mercury source. This research examines the Hg contamination gradient from a land-based coal mine to the surrounding coastal environment to quantify the impact of local sources. Total mercury and PAH (Σ14PAH) were measured in terrestrial and marine sediments as well as in marine biota. Samples were collected at the mine and two reference sites. Mercury and Σ14PAH concentrations in samples collected at the mine site were significantly higher than those at the reference sites. This was also found in the biota samples, although less pronounced. This work addresses the complexities of interpreting data concerning very low contaminant levels in a relatively pristine environment. A clear correlation between PAH and Hg concentration in sediment was found, although a large number of samples had levels below detection limits. PAH profiles, hierarchical clustering, and molecular diagnostic ratios provided further insight into the origin of PAHs and Hg, showing that signatures in sediments from the nearest reference site were more similar to the mine, which was not the case for the other reference site. The observed exposure radius from the mine was small and diluted from land to water to marine biota. Due to low contamination levels and variable PAH profiles, marine biota was less suitable for tracing the exposure radius for this local land-based Hg source. With an expected increase in mobility and availability of contaminants in the warming Arctic, changes in input of PAHs and Hg from land-based sources to the marine system need close monitoring.

Graphical abstract
Can Machine Learning Provide Understanding? How Cosmologists Use Machine Learning to Understand Observations of the Universe
Authors: Meskhidze Helen
Published: July 2021

The increasing precision of observations of the large-scale structure of the universe has created a problem for simulators: running the simulations necessary to interpret these observations has become impractical. Simulators have thus turned to machine learning (ML) algorithms instead. Though ML decreases computational expense, one might be worried about the use of ML for scientific investigations: How can algorithms that have repeatedly been described as black-boxes deliver scientific understanding? In this paper, I investigate how cosmologists employ ML, arguing that in this context, ML algorithms should not be considered black-boxes and can deliver genuine scientific understanding. Accordingly, understanding the methodological role of ML algorithms is crucial to understanding the types of questions they are capable of, and ought to be responsible for, answering.
Clothes, Sensory Experiences and Autism: Is Wearing the Right Fabric Important?
Authors: Kyriacou Chrysovalanto , Forrester-Jones Rachel , Triantafyllopoulou Paraskevi
Published: July 2021

Tactile defensiveness in autistic individuals is the least investigated sensory modality. The current multi-component, explorative study aimed to understand the experiences of ten autistic adults regarding tactile defensiveness and fabrics, using semi-structured, one-to-one interviews. Participants were asked to discuss the effects of seven provided samples of fabrics and were also asked to bring their ‘favourite’ fabric (s) and express their thoughts about their choices. Using Interpretative Phenomenological Analysis and Content Analysis, the findings showed that some fabrics can impact individuals’ reported wellbeing. Participants’ experiences with several stimuli appeared to have helped them implement coping strategies. By understanding tactile defensiveness, society could move towards increasing autism-friendly approaches with appropriate fabrics. Recommendations for future research, policy and practice are also discussed.
Sensory Processing in Williams Syndrome: Individual differences and changes over time
Authors: Powell Bradley , Van Herwegen Jo
Published: July 2021

This study examined individual differences as well as the development of sensory processing difficulties in children with Williams syndrome (WS) using a cross-sectional (Experiment 1) and longitudinal design (Experiment 2). In Experiment 1, a clustering approach of sensory processing scores suggested two groups. Experiment 2 showed that the clusters identified in Experiment 1 were not stable across development, especially for those with high sensory impairments at either time point. Yet, most children experienced high impairments in sensory registration at both time points, suggesting impaired registration is a core phenotype of sensory processing in children with WS across development. Possible mechanisms, limitations and implications are discussed.
Effect of salinity and pH on growth, phycoerythrin, and non-volatile umami taste active compound concentration of Rhodomonas salina using a D-optimal design approach
Authors: Latsos Christos , Bakratsas Georgios , Moerdijk Tanja , van Houcke Jasper , Timmermans Klaas R.
Published: July 2021

The cryptophyte Rhodomonas salina is widely used in aquaculture due to its high nutritional profile. This study aims to investigate the effect of salinity and pH on the growth, phycoerythrin concentrations, and concentrations of non-volatile umami taste active compounds of R. salina, using a design of experiment approach. Rhodomonas salina was cultivated in a flat-panel photobioreactor in turbidostat mode in a range of salinity (20–40 ‰) and pH (6.5–8.5). The strain was able to grow steadily under all conditions, but the optimal productivity of 1.17 g dry weight L−1 day−1 was observed in salinity 30 ‰ and pH 7.5. The phycoerythrin concentration was inversely related to productivity, presenting higher values in conditions that were not optimal for the growth of R. salina, 7% of dry weight at salinity 40 ‰, and pH 8.5. The identification of the umami taste of R. salina was based on the synergistic effect of umami compounds 5′-nucleotides (adenosine 5′-monophosphate, guanosine 5′-monophosphate, inosine 5′-monophosphate) and free amino acids (glutamic and aspartic acids), using the equivalent umami concentration (EUC). The results indicated that an increase in pH induces the accumulation of 5′-nucleotides, resulting in an EUC of 234 mg MSG g−1 at a salinity of 40 and pH 8.5. The EUC values that were observed in R. salina were higher compared to other aquatic animals, a fact that makes R. salina promising for further research and application in the food and feed sectors.
Closed-form time derivatives of the equations of motion of rigid body systems
Authors: Müller Andreas , Kumar Shivesh
Published: July 2021

Derivatives of equations of motion (EOM) describing the dynamics of rigid body systems are becoming increasingly relevant for the robotics community and find many applications in design and control of robotic systems. Controlling robots, and multibody systems comprising elastic components in particular, not only requires smooth trajectories but also the time derivatives of the control forces/torques, hence of the EOM. This paper presents the time derivatives of the EOM in closed form up to second-order as an alternative formulation to the existing recursive algorithms for this purpose, which provides a direct insight into the structure of the derivatives. The Lie group formulation for rigid body systems is used giving rise to very compact and easily parameterized equations.
The parallelism argument and the problem of moral luck
Authors: Nyman Anna
Published: July 2021

Robert Hartman’s parallelism argument aims to show that resultant moral luck exists. The gist of the argument is this: because there is circumstantial moral luck in a particular circumstantial luck scenario and that scenario is analogous in important ways to a particular resultant luck scenario, the resultant luck scenario is plausibly an instance of resultant moral luck (and hence, resultant moral luck exists). I argue that there is a principled way of denying that circumstantial moral luck is present in the circumstantial luck scenario. Doing so is not enough, however, to reject Hartman’s general analogical line of reasoning since an alternative parallelism argument based on a resultant luck scenario and a circumstantial luck scenario of another kind can be made. Nevertheless, I argue that the analogy between the circumstantial luck scenario and the resultant luck scenario in both the alternative parallelism argument and its original counterpart is too weak to support the claim that resultant moral luck is present in the resultant luck scenario.
Responsible Management Education in Time of Crisis: A Conceptual Framework for Public Business Schools in Egypt and Similar Middle Eastern Context
Authors: Mousa Mohamed , Massoud Hiba , Ayoubi Rami
Published: July 2021

Recent studies show that the adoption of RME scenarios is still a matter of concern for non-western countries ((Mousa et al., Journal of Management Development 38:681–696, 2019), 2021a, 2021b). In this paper, we theoretically propose the potential direction of RME scenarios that business schools in Egypt and other similar cultural context to implement through articulating the main antecedents of RME before and after Covid-19. we used the method of multilevel research by combining different theoretical approaches. As an outcome of our analysis, we developed five propositions which form the main antecedents of RME in Egypt and similar regional Middle East business schools before and after Covid-19.
The expanded prostate cancer index composite short form (EPIC-26) for measuring health-related quality of life: content analysis of patients’ spontaneous comments written in survey margins
Authors: Talvitie Anna-Maija , Ojala Hanna , Tammela Teuvo , Pietilä Ilkka
Published: July 2021

Introduction

This study investigates comments that prostate cancer patients spontaneously write in the margins of the Expanded Prostate Cancer Index Short Form (EPIC-26) questionnaire. We aim to show the possible barriers that patients face while answering the survey, and to consider how these barriers may affect the response data generated. We investigate the kind of information patients’ comments on EPIC-26 contain, and patients’ motivations to provide this information. We also study why some EPIC domains spark more comments than others.

Method

We analyzed 28 pages of transcribed comments and four pages of supplementary letters from our survey participants (n = 496). Using inductive content analysis, we generated 10 categories describing the content of participants’ comments, and four themes demonstrating their motives for commenting. The comments regarding each EPIC domain were quantified to discover any differences between domains.

Results

The sexual domain of EPIC-26 provoked over half of all comments. Patients without recent sexual activity or desire had difficulties answering sexual function questions 8–10. The lack of instructions on whether to take erectile aid use into account when answering erectile function questions led to a diversity of answering strategies. Patients with urinary catheters could not find suitable answer options for questions 1–4. All domains sparked comments containing additional information about experienced symptoms.

Conclusion

Patients are mainly willing to report their symptoms, but a lack of suitable answer options causes missing data and differing answering strategies in the sexual and urinary domains of EPIC-26, weakening the quality of the response data received.
The Myth of Equal Opportunity in Germany? Wage Inequality and the Role of (Non-)academic Family Background for Differences in Capital Endowments and Returns on the Labour Market
Authors: Consiglio Valentina S. , Sologon Denisa M.
Published: July 2021

While providing equal opportunities to all members of society independent of an individual’s socio-economic background is a major objective of German policy makers, educational opportunities of children with a non-academic family background are still unequally obstructed. When analysing the labour market implications of this disadvantage, social capital as an additional source of inequality often lacks attention. Drawing on the instrumental value of rather loose contacts (i.e. weak ties) on the labour market as revealed by Granovetter (Getting a job. A study of contacts and careers, The University of Chicago Press, Cambridge, 1974), this paper goes beyond the human capital approach and includes a measure of instrumental social capital in the form of weak-tie career support in the earnings function. Applying an Oaxaca-Blinder decomposition and quantile regressions, we find a significant average wage gap between those with and without an academic family background. A large part can be explained by deficits that those from less educated families incur with respect to human and instrumental social capital: Lower educational attainment accounts for more than half of the wage gap between the two groups while fewer career support explains around five percent of the differential. Additionally, a non-academic family background is associated with a significant deficit in returns to their instrumental social capital along the wage distribution. The findings therefore suggest that inequalities of opportunity on the German labour market occur beyond the education system, as not only the quantity but also the quality of career supporting networks of those from a non-academic family are inferior.
Elicitation of solid callus cultures of Salvia miltiorrhiza Bunge with salicylic acid and a synthetic auxin (1-naphthaleneacetic acid)
Authors: Szymczyk Piotr , Szymańska Grażyna , Kochan Ewa , Szemraj Janusz , Grąbkowska Renata
Published: July 2021

The presented study analyses the influence of salicylic acid (SA) and the synthetic auxin 1-naphthaleneacetic acid (NAA) on total tanshinone level and on dihydrotanshinone (DHT), cryptotanshinone (CT), tanshinine I (TI) and tanshinone IIA (TIIA) level in Salvia miltiorrhiza callus cultures growing on solid Murashige and Skoog (MS) medium. The influence of SA and NAA was evaluated at 10-day intervals throughout a 80-day treatment period. SA was applied at 0.1, 0.2 and 0.4 mM, and NAA at 2.69, 13.43, 26.85 and 40.28 μM. DHT, CT, TI and TIIA concentrations were measured using HPLC. NAA did not increase the concentration of any tanshinone. SA increased content in a concentration- and time-dependent manner; however, the yields were relatively low, possibly due to the metabolic specificity of S. miltiorrhiza cultivars in Poland. Total tanshinone concentration reached 226.38 ± 37.33 μg g−1 DW after 50 days of 0.4 mM SA elicitation. After 50 days of SA elicitation, the following maximum tanshinone concentrations were observed for 0.4 mM SA: DHT (71.58 ± 12.72 μg g−1 DW), CT (108.54 ± 18.29 μg g−1 DW), TI (29.50 ± 4.13 μg g−1 DW) and TIIA (16.75 ± 2.74 μg g−1 DW). To account for these observed differences in tanshinone biosynthesis, the distribution of SA and auxin responsive cis-active motif in the proximal promoters of the mevalonic acid, methylerythritol-4-phosphate and tanshinone-precursor biosynthesis pathway genes was evaluated in A. thaliana and S. miltiorrhiza. Our findings indicate that the SA-responsive cis-active elements have a much broader distribution than those recognized by auxin-responsive transcription factors.
CO$$_{2}$$ Convection in Hydrocarbon Under Flowing Conditions
Authors: Mykkeltvedt Trine S. , Gasda Sarah E. , Sandve Tor Harald
Published: July 2021

Carbon-neutral oil production is one way to improve the sustainability of petroleum resources. The emissions from produced hydrocarbons can be offset by injecting capture CO$$_{2}$$2from a nearby point source into a saline aquifer for storage or a producing oil reservoir. The latter is referred to as enhanced oil recovery (EOR) and would enhance the economic viability of CO$$_{2}$$2sequestration. The injected CO$$_{2}$$2will interact with the oil and cause it to flow more freely within the reservoir. Consequently, the overall recovery of oil from the reservoir will increase. This enhanced oil recovery (EOR) technique is perceived as the most cost-effective method for disposing captured CO$$_{2}$$2emissions and has been performed for many decades with the focus on oil recovery. The interaction between existing oil and injected CO$$_{2}$$2needs to be fully understood to effectively manage CO$$_{2}$$2migration and storage efficiency. When CO$$_{2}$$2and oil mix in a fully miscible setting, the density can change non-linearly and cause density instabilities. These instabilities involve complex convective-diffusive processes, which are hard to model and simulate. The interactions occur at the sub-centimeter scale, and it is important to understand its implications for the field scale migration of CO$$_{2}$$2and oil. In this work, we simulate gravity effects, namely gravity override and convective mixing, during miscible displacement of CO$$_{2}$$2and oil. The flow behavior due to the competition between viscous and gravity effects is complex, and can only be accurately simulated with a very fine grid. We demonstrate that convection occurs rapidly, and has a strong effect on breakthrough of CO$$_{2}$$2at the outlet. This work for the first time quantifies these effects for a simple system under realistic conditions.
Tumor response evaluation in patients with malignant melanoma undergoing immune checkpoint inhibitor therapy and prognosis prediction using 18F-FDG PET/CT: multicenter study for comparison of EORTC, PERCIST, and imPERCIST
Authors: Kitajima Kazuhiro , Watabe Tadashi , Nakajo Masatoyo , Ishibashi Mana , Daisaki Hiromitsu , Soeda Fumihiko , Tanemura Atsushi , Kanekura Takuro , Yamazaki Naoya , Ito Kimiteru
Published: July 2021

Objective

In malignant melanoma patients treated with immune checkpoint inhibitor (ICI) therapy, three different FDG-PET criteria, European Organization for Research and Treatment of Cancer (EORTC), PET Response Criteria in Solid Tumors (PERCIST), immunotherapy-modified PERCIST (imPERCIST), were compared regarding response evaluation and prognosis prediction using standardized uptake value (SUV) harmonization of results obtained with various PET/CT scanners installed at different centers.

Materials and methods

Malignant melanoma patients (n = 27) underwent FDG-PET/CT examinations before and again 3 to 9 months after therapy initiation (nivolumab, n = 21; pembrolizumab, n = 6) with different PET scanners at five hospitals. EORTC, PERCIST, and imPERCIST criteria were used to evaluate therapeutic response, then concordance of the results was assessed using Cohen’s κ coefficient. Log-rank and Cox methods were employed to determine progression-free (PFS) and overall (OS) survival.

Results

Complete metabolic response (CMR)/partial metabolic response (PMR)/stable metabolic disease (SMD)/progressive metabolic disease (PMD) with harmonized EORTC, PERCIST, and imPERCIST was seen in 3/5/4/15, 4/5/3/15, and 4/5/5/13 patients, respectively. Nearly perfect concordance between each pair of criteria was noted (κ = 0.939–0.972). Twenty patients showed progression and 14 died from malignant melanoma after a median 19.2 months. Responders (CMR/PMR) showed significantly longer PFS and OS than non-responders (SMD/PMD) (harmonized EORTC: p < 0.0001 and p = 0.011; harmonized PERCIST: p < 0.0001 and p = 0.0012; harmonized imPERCIST: p < 0.0001 and p = 0.0012, respectively).

Conclusions

All harmonized FDG-PET criteria (EORTC, PERCIST, imPERCIST) showed accuracy for response evaluation of ICI therapy and prediction of malignant melanoma patient prognosis. Additional studies to determine their value in larger study populations will be necessary.
Necessary Conditions for Boundedness of Translation Operator in de Branges Spaces
Authors: Bellavita Carlo
Published: July 2021

The translation operator is bounded in the Paley–Wiener spaces and, more generally, in the Bernstein spaces. The goal of this paper is to find some necessary conditions for the boundedness of the translation operator in the de Branges spaces, of which the Paley–Wiener spaces are special cases. Indeed, if the vertical translation operator $$T_\tau $$

T
τ

defined on the de Branges space $${\mathcal H}(E)$$

H
(
E
)

is bounded, then a suitably defined measure $$d\mu (z)$$

d
μ
(
z
)

is a Carleson measure for the associated model space $$K(\Theta )$$

K
(
Θ
)

. This relation allows us to state necessary conditions for the boundedness of the vertical translation $$T_\tau $$

T
τ

. Finally, similar results are also obtained for the horizontal translation $$T_\sigma $$

T
σ

.
Cutaneous body image in psoriasis: The role of attachment style and alexithymia
Authors: Troisi Alfonso , Nanni Roberta Croce , Giunta Alessandro , Manfreda Valeria , Del Duca Ester , Criscuolo Silvia , Bianchi Luca , Esposito Maria
Published: July 2021

The aim of this study was to estimate the contribution of adult attachment style and alexithymia to cutaneous body image in patients with psoriasis while controlling for the confounding effects of disease severity and depressive symptoms. Participants were 107 consecutive patients (60% women) with a diagnosis of plaque-type psoriasis. Cutaneous body dissatisfaction was measured with the Cutaneous Body Image Scale (CBIS) and disease severity with the Psoriasis Area and Severity Index (PASI). Depressive symptoms, attachment style and alexithymia were assessed with the Beck Depression Inventory (BDI), the Attachment Style Questionnaire (ASQ) and the Toronto Alexithymia Scale (TAS-20), respectively. Hierarchical regression analysis showed that, independently from the severity of skin disease and depressive symptoms, patients with an insecure-avoidant attachment style and higher levels of alexithymia reported greater cutaneous body dissatisfaction. Because of the cross-sectional design, the causal relationship between avoidant attachment, alexithymia and cutaneous body image cannot be determined. There was no control group. Clinical assessment of patients with psoriasis should include attachment style and alexithymia among the psychological variables related to cutaneous body dissatisfaction.
Optimization of injection dose in 18F-FDG PET/CT based on the 2020 national diagnostic reference levels for nuclear medicine in Japan
Authors: Sagara Hiroaki , Inoue Kazumasa , Yaku Hideki , Ohsawa Amon , Someya Takashi , Yanagisawa Kaori , Ohashi Shuhei , Ishigaki Rikuta , Wakabayashi Masashi , Muramatsu Yoshihisa , Fujii Hirofumi
Published: July 2021

Objective

Recently, the national diagnostic reference levels (DRLs) in Japan were revised as the DRLs 2020, wherein the body weight-based injection dose optimization in positron emission tomography/computed tomography using 18F-fluoro-2-deoxy-D-glucose (18F-FDG PET/CT) was first proposed. We retrospectively investigated the usefulness of this optimization method in improving image quality and reducing radiation dose.

Methods

A total of 1,231 patients were enrolled in this study. A fixed injection dose of 240 MBq was administered to 624 patients, and a dose adjusted to 3.7 MBq/kg body weight was given to 607 patients. The patients with body weight-based injection doses were further divided according to body weight: group 1 (≤ 49 kg), group 2 (50–59 kg), group 3 (60–69 kg), and group 4 (≥ 70 kg). The effective radiation dose of FDG PET was calculated using the conversion factor of 0.019 mSv/MBq, per the International Commission on Radiological Protection publication 106. Image quality was assessed using noise equivalent count density (NECdensity), which was calculated by excluding the counts of the brain and bladder. The usefulness of the injection dose optimization in terms of radiation dose and image quality was analyzed.

Results

The body weight-based injection dose optimization significantly decreased the effective dose by 11%, from 4.54 ± 0.1 mSv to 4.05 ± 0.8 mSv (p < 0.001). Image quality evaluated by NECdensity was also significantly improved by 10%, from 0.39 ± 0.1 to 0.43 ± 0.2 (p < 0.001). In no case did NECdensity deteriorate when the effective dose was decreased. In group 1, the dose decreased by 32%, while there was no significant deterioration in NECdensity (p = 0.054). In group 2, the dose decreased by 17%, and the NECdensity increased significantly (p < 0.01). In group 3, the dose decreased by 3%, and the NECdensity increased significantly (p < 0.01). In group 4, the dose increased by 14%, but there was no significant change in the NECdensity (p = 0.766).

Conclusion

Body weight-based FDG injection dose optimization contributed to not only the reduction of effective dose but also the improvement of image quality in patients weighing between 50 and 69 kg.
Familiarity and Complexity during a Takeover in Highly Automated Driving
Authors: Scharfe-Scherf Marlene Susanne Lisa , Russwinkel Nele
Published: July 2021

This paper shows, how objective complexity and familiarity impact the subjective complexity and the time to make an action decision during the takeover task in a highly automated driving scenario. In the next generation of highly automated driving the driver remains as fallback and has to take over the driving task whenever the system reaches a limit. It is thus highly important to develop an assistance system that supports the individual driver based on information about the drivers’ current cognitive state. The impact of familiarity and complexity (objective and subjective) on the time to make an action decision during a takeover is investigated. To produce replicable driving scenarios and manipulate the independent variables situation familiarity and objective complexity, a driving simulator is used. Results show that the familiarity with a traffic situation as well as the objective complexity of the environment significantly influence the subjective complexity and the time to make an action decision. Furthermore, it is shown that the subjective complexity is a mediator variable between objective complexity/familiarity and the time to make an action decision. Complexity and familiarity are thus important parameters that have to be considered in the development of highly automated driving systems. Based on the presented mediation effect, the opportunity of gathering the drivers’ subjective complexity and adapting cognitive assistance systems accordingly is opened up. The results of this study provide a solid basis that enables an individualization of the takeover by implementing useful cognitive modeling to individualize cognitive assistance systems for highly automated driving.
Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model
Authors: Xu Xiaoyan , Sun Yaqin , Cen Xufeng , Shan Bing , Zhao Qingwei , Xie Tingxue , Wang Zhe , Hou Tingjun , Xue Yu , Zhang Mengmeng , Peng Di , Sun Qiming , Yi Cong , Najafov Ayaz , Xia Hongguang
Published: July 2021

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer’s disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβ plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.
Abdominal incision defect following AAA-surgery (AIDA): 2-year results of prophylactic onlay-mesh augmentation in a multicentre, double-blind, randomised controlled trial
Authors: Honig S. , Diener H. , Kölbel T. , Reinpold W. , Zapf A. , Bibiza-Freiwald E. , Debus E. S. ,   for AIDA study group, Breuer Peter , Daum Harald , Eckstein Hans-Henning , Gahlen Johannes , Grommes Jochen , Hupp Thomas , Kellersmann Richard , Kortmann Helmut , Verhoeven Eric , Wenk Heiner
Published: July 2021

The reported incidence of incisional hernia following repair of abdominal aortic aneurysm (AAA) via midline laparotomy is up to 69%. This prospective, multicenter, double-blind, randomised controlled trial was conducted at eleven hospitals in Germany. Patients aged 18 years or older undergoing elective AAA-repair via midline incision were randomly assigned using a computer-generated randomisation sequence to one of three groups for fascial closure: with long-term absorbable suture (MonoPlus®, group I), long-term absorbable suture and onlay mesh reinforcement (group II) or extra long-term absorbable suture (MonoMax®, group III). The primary endpoint was the incidence of incisional hernia within 24 months of follow-up, analysed by intention to treat. Physicians conducting the postoperative visits and the patients were blinded. Between February 2011 and July 2013, 104 patients (69.8 ± 7.7 years) were randomised, 99 of them received a study intervention. The rate of incisional hernia within 24 months was not significantly reduced with onlay mesh augmentation compared to primary suture (p = 0.290). Furthermore, the rate of incisional hernia did not differ significantly between fascial closure with slow and extra long-term absorbable suture (p = 0.111). Serious adverse events related to study intervention occurred in five patients (5.1%) from treatment groups II and III. Wound healing disorders were more frequently seen after onlay mesh implantation on the day of discharge (p = 0.010) and three (p = 0.009) and six (p = 0.023) months postoperatively. The existing evidence on prophylactic mesh augmentation in patients undergoing AAA-repair via midline laparotomy probably needs critical review. As the implementation of new RCTs is considered difficult due to the increasing number of endovascular AAA treated, registry studies could help to collect and evaluate data in cases of open AAA-repair. Comparisons between prophylactic mesh implantation and the small bite technique are also required. Trial registration: ClinicalTrials.gov Identifier: NCT01353443. Funding Sources: Aesculap AG, Tuttlingen, Germany.
On the norm-preservation of squares in real algebra representation
Authors: Albiac F. , Blasco O. , Briem E.
Published: July 2021

One of the main results of the article Gelfand theory for real Banach algebras, recently published in [Rev R Acad Cienc Exactas Fís Nat Ser A Mat RACSAM 114(4):163, 2020] is Proposition 4.1, which establishes that the norm inequality $$\Vert a^{2}\Vert \le \Vert a^{2}+b^{2}\Vert $$

‖

a
2

‖
≤
‖

a
2

+

b
2

‖

for $$a,b\in {\mathcal {A}}$$

a
,
b
∈
A

is sufficient for a commutative real Banach algebra $${\mathcal {A}}$$
A
with a unit to be isomorphic to the space $${\mathcal {C}}_{{\mathbb {R}}}({\mathcal {K}})$$

C
R

(
K
)

of continuous real-valued functions on a compact Hausdorff space $${\mathcal {K}}$$
K
. Moreover, in this proposition is also shown that if the above condition (which involves all the operations of the algebra) holds, then the real-algebra isomorphism given by the Gelfand transform preserves the norm of squares. A very natural question springing from the above-mentioned result is whether an isomorphism of $${\mathcal {A}}$$
A
onto $${\mathcal {C}}_{{\mathbb {R}}}({\mathcal {K}})$$

C
R

(
K
)

is always norm-preserving of squares. This note is devoted to providing a negative answer to this problem. To that end, we construct algebra norms on spaces $${\mathcal {C}}_{{\mathbb {R}}}({\mathcal {K}})$$

C
R

(
K
)

which are $$(1+\epsilon )$$

(
1
+
ϵ
)

-equivalent to the sup-norm and with the norm of the identity function equal to 1, where the norm of every nonconstant function is different from the standard sup-norm. We also provide examples of two-dimensional normed real algebras $${\mathcal {A}}$$
A
where $$\Vert a^2\Vert \le k \Vert a^2+b^2\Vert $$

‖

a
2

‖
≤
k
‖

a
2

+

b
2

‖

for all $$a,b\in {\mathcal {A}}$$

a
,
b
∈
A

, for some $$k>1$$

k
>
1

, but the inequality fails for $$k=1$$

k
=
1

.
3D printing of patient-specific implants for osteochondral defects: workflow for an MRI-guided zonal design
Authors: Kilian David , Sembdner Philipp , Bretschneider Henriette , Ahlfeld Tilman , Mika Lydia , Lützner Jörg , Holtzhausen Stefan , Lode Anja , Stelzer Ralph , Gelinsky Michael
Published: July 2021

Magnetic resonance imaging (MRI) is a common clinical practice to visualize defects and to distinguish different tissue types and pathologies in the human body. So far, MRI data have not been used to model and generate a patient-specific design of multilayered tissue substitutes in the case of interfacial defects. For orthopedic cases that require highly individual surgical treatment, implant fabrication by additive manufacturing holds great potential. Extrusion-based techniques like 3D plotting allow the spatially defined application of several materials, as well as implementation of bioprinting strategies. With the example of a typical multi-zonal osteochondral defect in anosteochondritis dissecans(OCD) patient, this study aimed to close the technological gap between MRI analysis and the additive manufacturing process of an implant based on different biomaterial inks. A workflow was developed which covers the processing steps of MRI-based defect identification, segmentation, modeling, implant design adjustment, and implant generation. A model implant was fabricated based on two biomaterial inks with clinically relevant properties that would allow for bioprinting, the direct embedding of a patient’s own cells in the printing process. As demonstrated by the geometric compatibility of the designed and fabricated model implant in a stereolithography (SLA) model of lesioned femoral condyles, a novel versatile CAD/CAM workflow was successfully established that opens up new perspectives for the treatment of multi-zonal (osteochondral) defects.

Graphic abstract
Survey of Musculoskeletal Injuries, Prehike Conditioning, and On-Trail Injury Prevention Strategies Self-Reported by Long-Distance Hikers on the Appalachian Trail
Authors: Chrusch Adam , Kavin Michelle
Published: July 2021

Introduction

Studies show that 40 to 60% of long-distance hikers on the Appalachian Trail experience musculoskeletal (MSK) injuries, but these studies are over a decade old. The increasing popularity of hiking and injury prevention advances warrant re-evaluation of injury patterns. We sought to determine the frequency of self-reported MSK injuries in long-distance hikers on the Appalachian Trail and associations with prehike conditioning and on-trail injury prevention strategies.

Methods

The Appalachian Trail Conservancy surveys registered hikers annually. Our orthopedic team added 10 questions specific to MSK injury, training, and equipment to the 2018 to 2019 electronic, cross-sectional Appalachian Trail Conservancy survey. Descriptive statistics and frequencies were calculated. Categorical variables were compared using χ2 analysis. Correlations were performed for associations between training and gear and MSK injury. Logistic regression assessed the effect of training on MSK injury. Statistical significance was set at P<0.05.

Results

Of 1295 respondents (52% response rate), 61% (n=791) reported MSK complaints; 28% (n=363) reported overuse/chronic MSK injuries, and 18% (n=238) reported acute injuries. MSK complaints resulted in 11% (n=147) stopping their hike. Respondents who did not train (13%, n=168) were significantly more likely to report an MSK injury (odds ratio 2.82; 95% CI 1.92–4.24; P<0.001). Strength training, stretch/yoga, and endurance training were associated with less injury (all P<0.001). Stabilizing footwear and poles/sticks were associated with fewer MSK complaints (all P<0.001).

Conclusions

Prehike training and hiking gear correlate with fewer injuries. Further research is warranted to elucidate whether promoting injury prevention strategies can reduce MSK injuries among long-distance hikers.