bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayes shrinkage estimator for consistency assessment of treatment effects in multi‐regional clinical trials
Authors: Adall Sisay W. , Xu Jin
Published: May 2021

The primary objective of a multi‐regional clinical trial is to investigate the overall efficacy of the drug across regions and evaluate the possibility of applying the overall trial result to some specific region. A challenge arises when there is not enough regional sample size. We focus on the problem of evaluating applicability of a drug to a specific region of interest under the criterion of preserving a certain proportion of the overall treatment effect in the region. We propose a variant of James‐Stein shrinkage estimator in the empirical Bayes context for the region‐specific treatment effect. The estimator has the features of accommodating the between‐region variation and finiteness correction of bias. We also propose a truncated version of the proposed shrinkage estimator to further protect risk in the presence of extreme value of regional treatment effect. Based on the proposed estimator, we provide the consistency assessment criterion and sample size calculation for the region of interest. Simulations are conducted to demonstrate the performance of the proposed estimators in comparison with some existing methods. A hypothetical example is presented to illustrate the application of the proposed method.
Radiological progression of COVID‐19 organizing pneumonia
Authors: Johari Bushra , Abdul Kadir Roqiah Fatmawati , Abd Ghani Farihah , Peter Alan Basil
Published: May 2021

Key message

It has recently been recognized that the clinical course of coronavirus disease 2019 (COVID‐19) and secondary organizing pneumonia (OP) tend to follow a subacute progression of respiratory illness. We present images of radiological progression of COVID‐19 pneumonia and secondary OP.
Degrees of necessity and of sufficiency: Further results and extensions, with an application to covid‐19 mortality in Austria
Authors: Gleiss Andreas , Henderson Robin , Schemper Michael
Published: May 2021

The purpose of this paper is to extend to ordinal and nominal outcomes the measures of degree of necessity and of sufficiency defined by the authors for dichotomous and survival outcomes in a previous paper. A cause, represented by certain values of prognostic factors, is considered necessary for an event if, without the cause, the event cannot develop. It is considered sufficient for an event if the event is unavoidable in the presence of the cause. The degrees of necessity and sufficiency, ranging from zero to one, are simple, intuitive functions of unconditional and conditional probabilities of an event such as disease or death. These probabilities often will be derived from logistic regression models; the measures, however, do not require any particular model. In addition, we study in detail the relationship between the proposed measures and the related explained variation summary for dichotomous outcomes, which are the common root for the developments for ordinal, nominal, and survival outcomes. We introduce and analyze the Austrian covid‐19 data, with the aim of quantifying effects of age and other potentially prognostic factors on covid‐19 mortality. This is achieved by standard regression methods but also in terms of the newly proposed measures. It is shown how they complement the toolbox of prognostic factor studies, in particular when comparing the importance of prognostic factors of different types. While the full model's degree of necessity is extremely high (0.933), its low degree of sufficiency (0.179) is responsible for the low proportion of explained variation (0.193).
Drilling under the COVID‐19 pandemic: A diary study of professional football players' mental health and workout performance
Authors: Sun Shuhua , Zhang Stephen X. , Jahanshahi Asghar Afshar , Jahanshahi Mehdi
Published: May 2021

There is little research examining how individuals’ daily experience during a pandemic affects their daily mental health status and work performance. To address this knowledge gap, we invoke conservation of resources theory to propose a resource‐based framework explaining how individuals’ daily COVID‐19 intrusive experience affects their daily mental health status (depression and anxiety) and work performance via its effect on daily psychosocial resource loss and gain; We further examine whether their supervisors’ daily visionary leadership behaviour alleviates the adverse impacts of daily COVID‐19 intrusive experience. Results, based on daily diary data from 139 football players (or soccer players) at 15 professional football clubs over 5 days during the COVID‐19 pandemic, provided support for our predictions. Our study extends the literature by providing previously undocumented evidence on daily within‐person variations in mental health status and work performance during a pandemic and by offering theory‐driven insights into the mediating and moderating mechanisms involved in within‐person variations.
Spectroscopy‐Assisted Label‐free Molecular Analysis of Live Cell Surface with Vertically Aligned Plasmonic Nanopillars
Authors: Zhang Chi , Siddhanta Soumik , Paria Debadrita , Li Yaozheng , Zheng Chao , Barman Ishan
Published: May 2021

A generalized label‐free platform for surface‐selective molecular sensing in living cells can transform the ability to examine complex events in the cell membrane. While vertically aligned semiconductor and metal‐semiconductor hybrid nanopillars have rapidly surfaced for stimulating and probing the intracellular environment, the potential of such constructs for selectively interrogating the cell membrane is surprisingly underappreciated. In this work, a new platform, entitled nano‐PROD (nano‐pillar based Raman optical detection), enables molecular recording by probing fundamental vibrational modes of membrane constituents of cells adherent on a large‐area silver‐coated silicon nanopillar substrate fabricated using a precursor solution‐based nanomanufacturing process. It is shown that the nano‐PROD platform sustains live cells in near‐physiological conditions, which can be directly profiled using surface‐enhanced Raman spectroscopy due to the confined electromagnetic field enhancement. The experimental results highlight the utility of the platform in probing specific cell surface markers for accurately recognizing the phenotypically identical prostate cancer cells, differing only in prostate‐specific membrane antigen expression. Due to its tunability, nano‐PROD has the promise to be readily extendable to other applications that can leverage its unique combination of nanoscale topographic features and molecular sensing capabilities, from stain‐free cytopathology inspection to understanding spatio‐mechanical regulation in membrane receptor function.
Multiscale 3D Bioprinting by Nozzle‐Free Acoustic Droplet Ejection
Authors: Jentsch Stefan , Nasehi Ramin , Kuckelkorn Christoph , Gundert Benedikt , Aveic Sanja , Fischer Horst
Published: May 2021

Bioprinting allows the manufacture of complex cell‐laden hydrogel constructs that can mature into tissue replacements in subsequent cell culture processes. The nozzles used in currently available bioprinters limit the print resolution and at dimensions below 100 µm clogging is expected. Most critically, the reduction of nozzle diameter also increases shear stress during printing. At critical shear stress, mechanical damage to printed cells triggers cell death. To overcome these limitations, a novel 3D bioprinting method based on the principle of acoustic droplet ejection (ADE) is introduced here. The absence of a nozzle in this method minimizes critical shear stress. A numerical simulation reveals that maximum shear stress during the ADE process is 2.7 times lower than with a Ø150 µm microvalve nozzle. Printing of cell clusters contained in droplets at the millimeter length scale, as well as in droplets the size of a single cell, is feasible. The precise 3D build‐up of cell‐laden structures is demonstrated and evidence is provided that there are no negative effects on stem cell morphology, proliferation, or differentiation capacities. This multiscale acoustic bioprinting technique thus holds promise for cell‐preserving creation of complex and individualized cell‐laden 3D hydrogel structures.
Node ages, relationships, and phylogenomic incongruence in an ancient gymnosperm lineage – Phylogeny of Ephedra revisited
Authors: Rydin Catarina , Blokzijl Ruben , Thureborn Olle , Wikström Niklas
Published: May 2021

Knowledge of relationships among plants has improved dramatically but for many groups, it still rests solely on information from the plastid genome. Consequently, only parts of the organisms’ evolutionary history are revealed. For the ancient gymnosperms of Ephedra (Gnetales), previous conclusions were based on both plastid and nuclear ribosomal DNA data, but results were typically poorly resolved and supported, presumably because of information poverty in the utilized gene regions. With the aim of resolving phylogenetic questions using more data, we sequenced the plastid genome and the nuclear ribosomal cistron for 50 specimens of Ephedra, largely covering the diversity of the genus. Phylogeny and node ages were estimated using maximum likelihood and Bayesian methods. However, instead of clarifying a few remaining uncertainties, we were left with new questions and incongruent results. Age estimates of the crown group of Ephedra vary considerably depending on utilized software and specified tree prior. Furthermore, previous estimates of the phylogeny of Ephedra have largely reflected information from nrITS, despite utilization of plastid gene regions as well. With analyses based on the entire plastid genome, completely new results emerge. Earlier conclusions of deep divergences in the genus are not supported, and there are ample examples of phylogenetic incongruence. Our study overturns conclusions in previous work and highlights that we still know fairly little about evolution in the ancient Ephedra lineage. How many species of Ephedra are there, and how are they related? How old is the crown group? Many species appear affected by a history of hybridization/introgression and/or polyploidy, but other processes may result in similar patterns and reasons for the detected incongruences must be further analyzed, preferably using population‐level sampling and low‐copy nuclear data.
Disease activation maps for subgingival dental calculus identification based on intelligent dental optical coherence tomography
Authors: Hsiao Tien‐Yu , Ho Yi‐Ching , Chen Mei‐Ru , Lee Shyh‐Yuan , Sun Chia‐Wei
Published: May 2021

During the treatment of periodontitis, removal of dental calculus is essential but still tricky despite developments of several imaging modalities. In this research, we propose a novel approach to provide an intuitive guidance, to automatically detect the present of subgingival calculus, and to identify the site of the lesion in optical coherence tomography images based on convolutional neural network model and the class activation maps technique. Our result shows good visualizations of dental calculus both in B‐scan and in volumetric view. We believe the improvement can break down the technical barrier and finally facilitate the prevalence of dental optical coherence tomography.
Plasmonic gold nanoagents for cancer imaging and therapy
Authors: Fu Qinrui , Zhang Xuan , Song Jibin , Yang Huanghao
Published: May 2021

Gold nanoparticles (AuNPs) are a popular material in the field of nanoscience because of their excellent biocompatibility and unique physical and chemical properties, and have been widely used in the biomedical field. AuNPs have a simple preparation method, controllable shape and size, high electron density and atomic number, superparamagnetic properties, and radiation sensitization effect, and their optical absorbance can be adjusted to the required biological window; thus, AuNPs are suitable for cancer imaging (photoacoustic imaging, computed tomography, and magnetic resonance imaging), photothermal therapy, and radiotherapy. AuNPs can also be used as carriers to load photosensitizers or chemotherapeutic agents, and therefore, can also be used in photodynamic therapy and chemotherapy. In summary, AuNPs and their assemblies can simultaneously realize cancer diagnosis and treatment, providing a new idea in the development of precision medical treatment.
Computational investigations of polymerase enzymes: Structure, function, inhibition, and biotechnology
Authors: Geronimo Inacrist , Vidossich Pietro , Donati Elisa , De Vivo Marco
Published: May 2021

DNA and RNA polymerases (Pols) are central to life, health, and biotechnology because they allow the flow of genetic information in biological systems. Importantly, Pol function and (de)regulation are linked to human diseases, notably cancer (DNA Pols) and viral infections (RNA Pols) such as COVID‐19. In addition, Pols are used in various applications such as synthesis of artificial genetic polymers and DNA amplification in molecular biology, medicine, and forensic analysis. Because of all of this, the field of Pols is an intense research area, in which computational studies contribute to elucidating experimentally inaccessible atomistic details of Pol function. In detail, Pols catalyze the replication, transcription, and repair of nucleic acids through the addition, via a nucleotidyl transfer reaction, of a nucleotide to the 3′‐end of the growing nucleic acid strand. Here, we analyze how computational methods, including force‐field‐based molecular dynamics, quantum mechanics/molecular mechanics, and free energy simulations, have advanced our understanding of Pols. We examine the complex interaction of chemical and physical events during Pol catalysis, like metal‐aided enzymatic reactions for nucleotide addition and large conformational rearrangements for substrate selection and binding. We also discuss the role of computational approaches in understanding the origin of Pol fidelity—the ability of Pols to incorporate the correct nucleotide that forms a Watson–Crick base pair with the base of the template nucleic acid strand. Finally, we explore how computations can accelerate the discovery of Pol‐targeting drugs and engineering of artificial Pols for synthetic and biotechnological applications.

This article is categorized under:

Structure and Mechanism > Reaction Mechanisms and Catalysis

Structure and Mechanism > Computational Biochemistry and Biophysics

Software > Molecular Modeling
Global patterns of offshore wind variability
Authors: West Chris G. , Smith Ronald B.
Published: May 2021

Using the 40‐year hourly gridded ERA5 reanalysis, we study the offshore patterns of wind variability using the probability density function (PDF) and the power spectral density (PSD). To summarize wind variability, we compute the Weibull parameters from the PDF and the PSD for six spectral bands: interannual, annual, multimonth, storm, diurnal, and semidiurnal. We characterize the storm spectral peak using a Gaussian function in
frequency space. These parameters are plotted along two pole‐to‐pole transects through the Atlantic Ocean at 25°W and the Pacific Ocean at 170°W longitude and at 16 current and proposed offshore wind sites. We test the idea that coastal and open‐ocean wind statistics may be described by a single set of meridional profiles.

In mid‐latitudes, the storm band variance exceeding 20 m2 s−2 dominates. The Weibull shape parameter is close to
. The storm interval varies from 4 to 7 days depending on location. In the Northern Hemisphere only, the annual variance is significant, exceeding 3 m2 s−2. In the equatorial region, we find steadier winds with small storm variance less than 3 m2 s−2. The Weibull shape parameter is
or greater, suggesting the possibility of a high capacity factor there. The storm interval can exceed 15 days. The equatorial zone has an annual wind variance reaching 2 m2 s−2, comparable to the storm variance. In the tropical Pacific, we find interannual variance associated with El Niño‐Southern Oscillation (ENSO). Semidiurnal variance is detected in the tropics from the atmospheric tide.
Sample and realized minimum variance portfolios: Estimation, statistical inference, and tests
Authors: Golosnoy Vasyl , Gribisch Bastian , Seifert Miriam Isabel
Published: May 2021

The global minimum variance portfolio (GMVP) is the starting point of the Markowitz mean‐variance efficient frontier. The estimation of the GMVP weights is therefore of much importance for financial investors. The GMVP weights depend only on the inverse covariance matrix of returns on financial risky assets, for this reason the estimated GMVP weights are subject to substantial estimation risk, especially in high‐dimensional portfolio settings. In this paper we review the recent literature on traditional sample estimators for the unconditional GMVP weights which are typically based on daily asset returns, as well as on modern realized estimators for the conditional GMVP weights based on intraday high‐frequency returns. We present various types of GMVP estimators with the corresponding stochastic results, discuss statistical tests and point on some directions for further research. Our empirical application illustrates selected properties of realized GMVP weights.

This article is categorized under:

Statistical and Graphical Methods of Data Analysis > Multivariate Analysis

Statistical and Graphical Methods of Data Analysis > Analysis of High Dimensional Data

Statistical Models > Multivariate Models
Seven challenges in the multiscale modeling of multicellular tissues
Authors: Fletcher Alexander G. , Osborne James M.
Published: May 2021

The growth and dynamics of multicellular tissues involve tightly regulated and coordinated morphogenetic cell behaviors, such as shape changes, movement, and division, which are governed by subcellular machinery and involve coupling through short‐ and long‐range signals. A key challenge in the fields of developmental biology, tissue engineering and regenerative medicine is to understand how relationships between scales produce emergent tissue‐scale behaviors. Recent advances in molecular biology, live‐imaging and ex vivo techniques have revolutionized our ability to study these processes experimentally. To fully leverage these techniques and obtain a more comprehensive understanding of the causal relationships underlying tissue dynamics, computational modeling approaches are increasingly spanning multiple spatial and temporal scales, and are coupling cell shape, growth, mechanics, and signaling. Yet such models remain challenging: modeling at each scale requires different areas of technical skills, while integration across scales necessitates the solution to novel mathematical and computational problems. This review aims to summarize recent progress in multiscale modeling of multicellular tissues and to highlight ongoing challenges associated with the construction, implementation, interrogation, and validation of such models.

This article is categorized under:

Reproductive System Diseases > Computational Models

Metabolic Diseases > Computational Models

Cancer > Computational Models
Introduction
Authors: Wang Chi-yuen , Manga Michael
Published: May 2021

“ … The waters that seem to have been cut off on the land of all communion with the sea, the springs, the lakes, were in extraordinary agitation in many distant lands at the same time.
Gravitational production of a conformal dark sector
Authors: Redi Michele , Tesi Andrea , Tillim Hannah
Published: May 2021

Abstract

Dark sectors with purely gravitational couplings to the Standard Model are unavoidably populated from the SM plasma by graviton exchange, and naturally provide dark matter candidates. We examine the production in the relativistic regime where the dark sector is approximately scale invariant, providing general analytical formulas that depend solely on the central charge of the dark sector. We then assess the relevance of interactions that can lead to a variety of phenomena including thermalisation, non-perturbative mass gaps, out-of-equilibrium phase transitions and cannibalism in the dark sector. As an illustrative example we consider the dark glueball scenario in this light and show it to be a viable dark matter candidate due to the suppression of gravitational production. We go on to extend these results to strongly coupled CFTs and their holographic duals at large-N with the dark dilaton as the dark matter candidate.
Moduli-dependent Calabi-Yau and SU(3)-structure metrics from machine learning
Authors: Anderson Lara B. , Gerdes Mathis , Gray James , Krippendorf Sven , Raghuram Nikhil , Ruehle Fabian
Published: May 2021

Abstract

We use machine learning to approximate Calabi-Yau and SU(3)-structure metrics, including for the first time complex structure moduli dependence. Our new methods furthermore improve existing numerical approximations in terms of accuracy and speed. Knowing these metrics has numerous applications, ranging from computations of crucial aspects of the effective field theory of string compactifications such as the canonical normalizations for Yukawa couplings, and the massive string spectrum which plays a crucial role in swampland conjectures, to mirror symmetry and the SYZ conjecture. In the case of SU(3) structure, our machine learning approach allows us to engineer metrics with certain torsion properties. Our methods are demonstrated for Calabi-Yau and SU(3)-structure manifolds based on a one-parameter family of quintic hypersurfaces in ℙ4.
Four-dimensional N = 1 theories, S-fold constraints on T-branes, and behaviors in IR and UV
Authors: Kimura Yusuke
Published: May 2021

Abstract

We analyze four-dimensional (4d) N = 1 superconformal field theories (SCFTs) obtained as deformations of 4d N = 2 SCFTs on S-folds by tilting 7-branes. Geometric compatibility with the structures of S-folds constrains the forms of T-branes. As a result, brane monodromies are constrained. We also discuss two 4d N = 1 theories on probe D3-branes, where the two theories behave identically in IR, but they originate from different theories in UV. Studying the global structure of their geometry is useful in constructing these two theories.
A $$ T\overline{T} $$-like deformation of the Skyrme model and the Heisenberg model of nucleon-nucleon scattering
Authors: Nastase Horatiu , Sonnenschein Jacob
Published: May 2021

Abstract

The Skyrme model, though it admits correctly a wide range of static properties of the nucleon, does not seem to reproduce properly the scattering behavior of nucleons at high energies. In this paper we present a $$ T\overline{T} $$
T

T
¯

-like deformation of it, inspired by a 1+1 dimensional model, in which boosted nucleons behave like shock waves. The scattering of the latter saturates the Froissart bound. We start by showing that 1+1 dimensional $$ T\overline{T} $$
T

T
¯

deformations of the free abelian pion action are in fact generalizations of the old Heisenberg model for nucleon-nucleon scattering, yielding the same saturation of the Froissart bound. We then deform the strong coupling limit of the bosonized action of multi-flavor QCD in two dimensions using the $$ T\overline{T} $$
T

T
¯

deformation of the WZW action with a mass term. We derive the classical soliton solution that corresponds to the nucleon, determine its mass and discuss its transformation into a shock-wave upon boosting. We uplift this action into a 3+1 dimensional $$ T\overline{T} $$
T

T
¯

-like deformation of the Skyrme action. We compare this deformed action to that of chiral perturbation theory. A possible holographic gravity dual interpretation is explored.
String scale thermal anti-de Sitter spaces
Authors: Ashok Sujay K. , Troost Jan
Published: May 2021

Abstract

We study finite temperature string scale AdS3 backgrounds. One background is AdS3× S1× T2 in which the anti-de Sitter space-time and the circle are at the radius $$ \sqrt{\alpha^{\prime }} $$

α
′

. Using path integral techniques, we show that the bulk spectrum includes a continuum of states as well as Ramond-Ramond ground states that agree with those of the symmetric orbifold of the two-torus after second quantization. We also examine the one-loop free energy of the background AdS3× S1 at curvature radius $$ \sqrt{2{\alpha}^{\prime }/3} $$

2

α
′

/
3

. In the space-time NSNS sector, the string theory spontaneously breaks conformal symmetry as well as R-charge conjugation symmetry. We prove that the minimum in the boundary energy is reached for a singly wound string. In the RR sector, we classify the infinite set of ground states with fractional R-charges. Moreover, we remark on the behaviour of critical temperatures as the curvature scale becomes smaller than the string scale.

In an appendix, we derive the Hawking-Page transition in string theory by integrating a world sheet one-point function.
Effective relational cosmological dynamics from quantum gravity
Authors: Marchetti Luca , Oriti Daniele
Published: May 2021

Abstract

We discuss the relational strategy to solve the problem of time in quantum gravity and different ways in which it could be implemented, pointing out in particular the fundamentally new dimension that the problem takes in a quantum gravity context in which spacetime and geometry are understood as emergent. We realize concretely the relational strategy we have advocated in the context of the tensorial group field theory formalism for quantum gravity, leading to the extraction of an effective relational cosmological dynamics from quantum geometric models. We analyze in detail the emergent cosmological dynamics, highlighting the improvements over previous work, the contribution of the quantum properties of the relational clock to it, and the interplay between the conditions ensuring a bona fide relational dynamics throughout the cosmological evolution and the existence of a quantum bounce resolving the classical big bang singularity.
Microwave scan and brain biomarkers to rule out intracranial hemorrhage: study protocol of a planned prospective study (MBI01)
Authors: Vedin Tomas , Bergenfeldt Henrik , Holmström Emanuel , Lundager-Forberg Jakob , Edelhamre Marcus
Published: May 2021

Purpose

The aim of this planned study is to evaluate the ability of a cranial microwave scanner in conjunction with nine brain biomarkers (Aβ40, Aβ42, GFAP, H-FABP, S100B, NF-L, NSE, UCH-L1 and IL-10) to detect and rule out traumatic intracranial hemorrhage in an emergency department setting. Traumatic brain injury is a world-wide topic of interest for researchers and clinicians. It affects 2% of the population per annum and presents challenges for physicians as patients’ initial signs and symptoms do not always correlate with the extent of brain injury. The gold standard for diagnosis of intracranial hemorrhage is head computerized tomography (CT) with the drawbacks of high cost and radiation exposure. A fast, secure way of diagnosing without these drawbacks has potential to make care more effective and reduce cost.

Methods

Study will be prospective and enroll adult, consenting patients with head trauma who seek emergency department care. Only patients where the treating physician prescribes a head-CT will be included. The microwave scan and blood sampling will be performed in close temporal proximity to the CT scan. Results will be analyzed with sensitivity, specificity and receiver operator characteristics analysis to provide the best combination of a number of biomarkers and the microwave scan.

Conclusion

This study will explore the diagnostic accuracy of a head microwave scanner in combination with biomarkers in ruling out intracranial hemorrhage in traumatic brain injury patients presenting to the emergency department. Potentially, this combined diagnostic approach could achieve both high sensitivity and high specificity, thereby reducing the need of CT-head scans when managing these patients.

Clinicaltrials.gov identifier: NCT04666766. Registered December 11, 2020.
Unklare chronische Schwindelsyndrome – Erfahrungen mit einem interdisziplinären stationären Diagnostikkonzept
Authors: Münst J. , Pudszuhn A. , v. Bernstorff M. , Obermueller T. , Erdur H. , Audebert H. J. , Rose M. , Reisshauer A. , Hoffmann I. , Schönfeld U. , Hofmann V. M.
Published: May 2021

Schwindel ist ein häufiges Leitsymptom. Insbesondere Patienten mit chronischen Schwindelsyndromen erleben eine deutliche Beeinträchtigung der Lebensqualität und bei Berufstätigen eine Einschränkung der Arbeitsfähigkeit. Folgen sind finanzielle und kapazitive Belastungen des Gesundheitssystems aufgrund von häufigen Mehrfachuntersuchungen und Krankschreibungen bis hin zur Erwerbsunfähigkeit der Betroffenen. Bei 150 Patienten mit in der ambulanten Diagnostik unklaren chronischen Schwindelsyndromen wurde auf der Grundlage eines strukturierten interdisziplinären stationären Diagnostikkonzepts bei über 90 % der Fälle mindestens eine die Beschwerden begründende Diagnose erhoben. Chronische Schwindelsyndrome sind häufig multifaktoriell bedingt. Bei mehr als der Hälfte der Patienten fanden sich u. a. psychosomatische (Begleit‑)Diagnosen. Zielführende therapeutische Empfehlungen können nur diagnosespezifisch erfolgen, weshalb in dauerhaft unklaren Fällen auch die Abklärung im Rahmen eines interdisziplinären stationären Diagnostikkonzepts sinnvoll und gerechtfertigt sein kann.
Genome-wide association mapping of sodium and potassium concentration in rice grains and shoots under alternate wetting and drying and continuously flooded irrigation
Authors: Chen Caijin , Travis Anthony J. , Hossain Mahmud , Islam Md Rafiqul , Price Adam H. , Norton Gareth J.
Published: May 2021

Key message

Identification of a large number of QTL and candidate genes for sodium accumulation in a field grown population of rice derived from theaussubpopulation.

Rice (Oryza sativaL.) is a globally important cereal crop. Sodium (Na+) and potassium (K+) are the major monovalent ions which affect rice growth, and exploring their uptake mechanisms will be useful for understanding rice biology. Since the balance of Na+and K+plays a significant role in adaptation of rice to salinity, that biology might inform the search for tolerance. In this study, the Na+and K+concentration and Na+/K+ratio in grains and shoots were analyzed in the Bengal and Assam Aus Panel grown in field conditions under continuously flooded (CF) and alternate wetting and drying (AWD) irrigation. Overall, AWD irrigation significantly reduced the Na+concentration and increased the K+concentration in shoots and grains compared to the plants grown under CF. Genome-wide association mapping was conducted on Na+, K+concentration and Na+/K+ratio with 2 million SNPs using an efficient mixed model. Only QTLs which contained more than two significant SNPs (p < 0.0001) and where at least one of these significant SNPs passed a 10% false discovery rate were reported. A total of 106 QTLs were identified as being associated with Na+concentration and Na+/K+ratio across all traits and field conditions, with 48 QTLs found in multiple traits and/or water conditions. Four notable QTLs (one each on chromosomes 1 and 11, two on chromosome 2) and the haplotype variants of four candidate genes (OsHKT1;5,OsNHX2,LOC_Os02g32490andOsFAD2_1) are discussed. The QTLs/candidate genes identified here could be useful for breeding rice that accumulates lower concentrations of sodium.
Gain and loss of function mutations in biological chemical reaction networks: a mathematical model with application to colorectal cancer cells
Authors: Sommariva Sara , Caviglia Giacomo , Piana Michele
Published: May 2021

This paper studies a system of Ordinary Differential Equations modeling a chemical reaction network and derives from it a simulation tool mimicking Loss of Function and Gain of Function mutations found in cancer cells. More specifically, from a theoretical perspective, our approach focuses on the determination of moiety conservation laws for the system and their relation with the corresponding stoichiometric surfaces. Then we show that Loss of Function mutations can be implemented in the model via modification of the initial conditions in the system, while Gain of Function mutations can be implemented by eliminating specific reactions. Finally, the model is utilized to examine in detail the G1-S phase of a colorectal cancer cell.
Correction to: Radiomics score predicts acute respiratory distress syndrome based on the initial CT scan after trauma
Authors: Röhrich Sebastian , Hofmanninger Johannes , Negrin Lukas , Langs Georg , Prosch Helmut
Published: May 2021

A Correction to this paper has been published: https://doi.org/10.1007/s00330-021-07995-7
The Carers’ Needs Assessment for Dementia (CNA-D): a validation study in the Italian population
Authors: Zucca Milena , Rubino Elisa , Vacca Alessandro , De Martino Paola , Caglio Marcella , Marcinnó Andrea , Bo Mario , Rainero Innocenzo
Published: May 2021

Background

Dementia has devastating consequences for families with important physical, psychological, social, and financial effects. Evaluation of caregiver’s needs may be an important step to reduce the burden of family caregivers of dementia patients. An Austrian scale, the Carers’ Needs Assessment for Dementia, is now available for measuring the caregiver’s needs. The aim of our study was to evaluate the psychometric properties of the Italian version of the CNA-D (iCNA-D).

Methods

A sample of 214 voluntary caregivers of dementia patients was recruited at the Department of Neuroscience, University of Turin (Italy). All participants were administered the iCNA-D. Validity and reliability of the instrument were evaluated using Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Symptom Checklist-90 (SCL-90), and the Italian version of Zarit Burden Interview (I-ZBI).

Results

The most common unmet need reported for the iCNA-D was “counseling and emotional support” (31.5%). This item demonstrates adequate reliability with moderate internal consistency for all “summary scores” of iCNA-D (α ≥ 0.75) and split-half correlation of more than 0.80 for two of them. We also found positive correlations in two out of three “summary scores” of iCNA-D and in the overall outcomes of BDI, BAI, SCL-90, and I-ZBI.

Conclusions

The iCNA-D could be a valid and reliable tool for a comprehensive assessment of needs and possible social supports proposed to relatives who take care of patients with dementia. Better understanding of family caregivers’ needs could improve planning of local services and reduce caregivers’ perception of distress and burden.
A study on using data clustering for feature extraction to improve the quality of classification
Authors: Piernik Maciej , Morzy Tadeusz
Published: May 2021

There is a certain belief among data science researchers and enthusiasts alike that clustering can be used to improve classification quality. Insofar as this belief is fairly uncontroversial, it is also very general and therefore produces a lot of confusion around the subject. There are many ways of using clustering in classification and it obviously cannot always improve the quality of predictions, so a question arises, in which scenarios exactly does it help? Since we were unable to find a rigorous study addressing this question, in this paper, we try to shed some light on the concept of using clustering for classification. To do so, we first put forward a framework for incorporating clustering as a method of feature extraction for classification. The framework is generic w.r.t. similarity measures, clustering algorithms, classifiers, and datasets and serves as a platform to answer ten essential questions regarding the studied subject. Each answer is formulated based on a separate experiment on 16 publicly available datasets, followed by an appropriate statistical analysis. After performing the experiments and analyzing the results separately, we discuss them from a global perspective and form general conclusions regarding using clustering as feature extraction for classification.
Structural change detection applying long-term seismic interferometry by deconvolution method to a modern civil engineering structure (New Zealand)
Authors: Skłodowska Anna Maria , Holden Caroline , Guéguen Philippe , Finnegan John , Sidwell Geoff
Published: May 2021

Pulse-wave propagation velocity and resonance frequency measured in civil engineering structures are both related to structural design. Monitoring their variation following seismic strong shaking provides information about the immediate building capacity. Joint-interpretation of frequency and velocity variation requires a better understanding of the processes controlling seismic structural health. In this study, we analysed 8 years of earthquake data recorded by the vertical array installed in the Te Puni building in Wellington, New Zealand, as part of the GeoNet building instrumentation programme. Co-seismic variations of pulse wave velocity and fundamental frequency are analysed and interpreted through a Timoshenko beam-like building model. This study shows that even though no structural damage was visually reported over the considered time of monitoring, co- and post-seismic variation of both parameters’ values are observed for almost all earthquakes, including a permanent shift following strong ground shaking. Variations of pulse-wave velocity and resonance frequency are cross-interpreted in terms of the building model. They reflect a time variant building response, correlated with the seismic loading. In addition, time delay of the pulse-wave velocity as a function of the building height provides relevant information on the location of the changes and confirms the efficient cross-interpretation of both methods for seismic Structural Health monitoring.
Maternal hypertensive disorders and neurodevelopmental disorders in offspring: a population-based cohort in two Nordic countries
Authors: Wang Hui , László Krisztina D. , Gissler Mika , Li Fei , Zhang Jun , Yu Yongfu , Li Jiong
Published: May 2021

Maternal hypertensive disorders during pregnancy (HDP) have been associated with neuropsychiatric problems in offspring. We aim to investigate the associations between specific types of maternal HDP and offspring neurodevelopmental disorders and further examine whether the timing of onset and severity of HDP would affect these associations. The study population consisted of 4,489,044 live-born singletons in Denmark during 1978–2012 and Sweden during 1987–2010. Maternal HDP was categorized into chronic hypertension, gestational hypertension, and pre-eclampsia; pre-eclampsia was further stratified according to timing (early-onset, late-onset), or severity (moderate, severe) of the disease. Neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID), were defined by ICD-coded register diagnosis. Cox regression was used to calculate hazard ratios (HR) while adjusting for potential confounders, and sibling analyses assessed the influence of unmeasured shared familial factors. Maternal HDP was associated with increased risks of ADHD (HR, 1.24; 95% confidence interval [CI], 1.20–1.28), ASD (1.29 [1.24–1.34]), and ID (1.58 [1.50–1.66]) in offspring, respectively, which was mostly driven by pre-eclampsia. The strongest associations were observed for early-onset and severe pre-eclampsia, and the corresponding HRs for ADHD, ASD and ID were 1.93 [1.73–2.16], 1.86 [1.61–2.15], and 3.99 [3.42–4.65], respectively. The results were similar in the sibling analyses. The associations between maternal HDP and offspring neurodevelopmental disorders were consistent across the subgroups of sex, preterm status, parity, maternal age and psychiatric disorders. Maternal HDP, especially early-onset pre-eclampsia, are associated with increased risks of ADHD, ASD, and ID in particular, independent of shared familial factors.
Automatic speech recognition in neurodegenerative disease
Authors: Schultz Benjamin G. , Tarigoppula Venkata S. Aditya , Noffs Gustavo , Rojas Sandra , van der Walt Anneke , Grayden David B. , Vogel Adam P.
Published: May 2021

Automatic speech recognition (ASR) could potentially improve communication by providing transcriptions of speech in real time. ASR is particularly useful for people with progressive disorders that lead to reduced speech intelligibility or difficulties performing motor tasks. ASR services are usually trained on healthy speech and may not be optimized for impaired speech, creating a barrier for accessing augmented assistance devices. We tested the performance of three state-of-the-art ASR platforms on two groups of people with neurodegenerative disease and healthy controls. We further examined individual differences that may explain errors in ASR services within groups, such as age and sex. Speakers were recorded while reading a standard text. Speech was elicited from individuals with multiple sclerosis, Friedreich’s ataxia, and healthy controls. Recordings were manually transcribed and compared to ASR transcriptions using Amazon Web Services, Google Cloud, and IBM Watson. Accuracy was measured as the proportion of words that were correctly classified. ASR accuracy was higher for controls than clinical groups, and higher for multiple sclerosis compared to Friedreich’s ataxia for all ASR services. Amazon Web Services and Google Cloud yielded higher accuracy than IBM Watson. ASR accuracy decreased with increased disease duration. Age and sex did not significantly affect ASR accuracy. ASR faces challenges for people with neuromuscular disorders. Until improvements are made in recognizing less intelligible speech, the true value of ASR for people requiring augmented assistance devices and alternative communication remains unrealized. We suggest potential methods to improve ASR for those with impaired speech.
HIV Care Engagement Among Justice-Involved and Substance Using People of Puerto Rican Origin Who are Living with HIV
Authors: Wiersema Janet J. , Teixeira Paul A. , Pugh Tracy , Cruzado-Quiñones Jacqueline , Jordan Alison O.
Published: May 2021

Persons living with diagnosed HIV (PLWDH) are overrepresented in correctional settings, as are Latinx including those of Puerto Rican (PR) origin. Little is known about this population’s HIV care engagement after incarceration. Semi-structured interviews were conducted with 23 PLWDH of PR origin incarcerated in NYC jails using the Behavioral Model for Vulnerable Populations as the theoretical basis. Most participants described a fragile connection to HIV care and inconsistent antiretroviral therapy adherence due to issues including substance use, poverty (e.g. homelessness), and other factors. Most were satisfied with their current communitybased providers and reported that their PR ethnicity and transnational ties to PR did not impact their HIV care, although some preferred Spanish-speaking providers. Greater access to stable housing and HIV care that is convenient to substance use treatment and other services appear to be the greatest needs of PLWDH of PR origin leaving jail.
Rare Events in Random Geometric Graphs
Authors: Hirsch Christian , Moka Sarat B. , Taimre Thomas , Kroese Dirk P.
Published: May 2021

This work introduces and compares approaches for estimating rare-event probabilities related to the number of edges in the random geometric graph on a Poisson point process. In the one-dimensional setting, we derive closed-form expressions for a variety of conditional probabilities related to the number of edges in the random geometric graph and develop conditional Monte Carlo algorithms for estimating rare-event probabilities on this basis. We prove rigorously a reduction in variance when compared to the crude Monte Carlo estimators and illustrate the magnitude of the improvements in a simulation study. In higher dimensions, we use conditional Monte Carlo to remove the fluctuations in the estimator coming from the randomness in the Poisson number of nodes. Finally, building on conceptual insights from large-deviations theory, we illustrate that importance sampling using a Gibbsian point process can further substantially reduce the estimation variance.
Emotionale Kompetenzen und psychische Gesundheit
Authors: Buruck Gabriele , Haitsch Sophia
Published: May 2021

Hintergrund

Im Jahr 2020 waren 5,7 Mio. Menschen in Gesundheits- und Pflegeberufen tätig. Der Kontakt mit anderen Menschen ist in diesen Berufen Teil des Arbeitsauftrags und der Mensch ist der Arbeitsgegenstand.

Ziel der Arbeit

Das Ziel der Arbeit ist die Untersuchung der Auswirkung von psychischer Belastung (Arbeitsintensität, Spielräume), emotionaler Erschöpfung und emotionalen Kompetenzen (Regulation) auf das psychische Wohlbefinden bei Beschäftigten in Gesundheitsberufen.

Material und Methoden

Die Erhebung der Querschnittstudie von 624 Beschäftigten aus der Altenpflege und dem Rettungsdienst (72,5 % weiblich) erfolgte im Rahmen zweier Projekte zur betrieblichen Gesundheitsförderung. Zum Einsatz kamen standardisierte validierte Verfahren, welche mittels Korrelationsanalysen sowie einer hierarchischen Regressionsanalyse zur Vorhersage des psychischen Wohlbefindens ausgewertet wurden.

Ergebnisse

Hohe Arbeitsintensität, hohe Spielräume, hohe emotionale Erschöpfung und eine hohe emotionale Kompetenz (Regulation) tragen zur Aufklärung des psychischen Wohlbefindens bei (R2 = 33 %).

Schlussfolgerung

Anhand der Ergebnisse wird deutlich, dass neben dem Erleben von Arbeit und Gesundheit auch emotionale Kompetenzen einen Einfluss auf die psychische Gesundheit bei Beschäftigten in Gesundheitsberufen haben. Damit leistet die Studie einen wichtigen Beitrag für die Entwicklung von Maßnahmen des betrieblichen Gesundheitsmanagements in diesen Berufsgruppen.
The Polygenic and Monogenic Basis of Paediatric Fractures
Authors: Ghatan S. , Costantini A. , Li R. , De Bruin C. , Appelman-Dijkstra N. M. , Winter E. M. , Oei L. , Medina-Gomez Carolina
Published: May 2021

Purpose of Review

Fractures are frequently encountered in paediatric practice. Although recurrent fractures in children usually unveil a monogenic syndrome, paediatric fracture risk could be shaped by the individual genetic background influencing the acquisition of bone mineral density, and therefore, the skeletal fragility as shown in adults. Here, we examine paediatric fractures from the perspective of monogenic and complex trait genetics.

Recent Findings

Large-scale genome-wide studies in children have identified ~44 genetic loci associated with fracture or bone traits whereas ~35 monogenic diseases characterized by paediatric fractures have been described.

Genetic variation can predispose to paediatric fractures through monogenic risk variants with a large effect and polygenic risk involving many variants of small effects. Studying genetic factors influencing peak bone attainment might help in identifying individuals at higher risk of developing early-onset osteoporosis and discovering drug targets to be used as bone restorative pharmacotherapies to prevent, or even reverse, bone loss later in life.
A negative feedback loop involving NF-κB/TIR8 regulates IL-1β-induced epithelial- myofibroblast transdifferentiation in human tubular cells
Authors: Jiang Keguo , Zhang Yuying , He Fan , Zhang Mingming , Li Tianyu , Tu Zhenzhen , Xu Deping , Zhang Min , Han Linzi , Guo Liyu , Zhou Haisheng , Wang Deguang
Published: May 2021

Renal tubular epithelial-myofibroblast transdifferentiation (EMT) plays a central role in the development of renal interstitial fibrosis (RIF). The profibrotic cytokine interleukin (IL)-1 and the IL-1 receptor (IL-1R) also participate in RIF development, and Toll/IL-1R 8 (TIR8), a member of the Toll-like receptor superfamily, has been identified as a negative regulator of IL-1R signaling. However, the functions of TIR8 in IL-1-induced RIF remain unknown. Here, human embryonic kidney epithelial cells (HKC) and unilateral ureteric obstruction (UUO)-induced RIF models on SD rats were used to investigate the functions of TIR8 involving IL-1β-induced EMT. We showed that IL-1β primarily triggers TIR8 expression by activating nuclear factor-κB (NF-κB) in HKC cells. Conversely, high levels of TIR8 in HKC cells repress IL-1β-induced NF-κB activation and inhibit IL-1β-induced EMT. Moreover, in vitro and in vivo findings revealed that TIR8 downregulation facilitated IL-1β-induced NF-κB activation and contributed to TGF-β1-mediated EMT in renal tubular epithelial cells. These results suggested that TIR8 exerts a protective role in IL-1β-mediated EMT and potentially represents a new target for RIF treatment.