bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors influencing work engagement among male nurses: A structural equation model
Authors: Wu Chao , Cheng Si‐zhe , Wu Jing , Zhang Yin‐juan , Lin Ya‐wei , Li Lu , Du Juan , Zhang Yu‐hai , Lang Hong‐juan
Published: October 2023

Aim

To investigate the male nurses' engagement in nursing work and the influencing factors.

Design

A cross‐sectional study.

Methods

A cross‐sectional survey was conducted in 13 hospitals in China to collect data from 328 male nurses from August to October 2021. A structural equation model design was tested with validated measurement instruments.

Results

The work engagement of male nurses in China was at a medium level. There was a high correlation of the male nurses' work engagement with career identity (r = 0.764, p < 0.01), career success (r = 0.735, p < 0.01) and social support (r = 0.477, p < 0.01). The linear multivariate regression analysis showed that career satisfaction (β = 0.393), career identity (β = 0.392) and subjective support (β = 0.116) entered regression equation of male nurses' work engagement (all p < 0.05). The structural equation model results showed that career identity and social support were the influencing factors of the male nurses' work engagement and the model explained variation of 66.4% variables.

Conclusion

To know the male nurses' work engagement and influencing factors in China has certain enlightening significance for male nurses themselves and nursing manager. On the one hand, it is necessary to enhance the male nurses' career recognition to nursing work. On the other hand, the society should provide more aid and support to the male nurses. Therefore, the male nurses could devote more into nursing work and promote the nursing development.
Structure–function relationships in ShKT domain peptides: ShKT‐Ts1 from the sea anemone Telmatactis stephensoni
Authors: Sanches Karoline , Ashwood Lauren M. , Olushola‐Siedoks Abisola Ave‐Maria , Wai Dorothy C. C. , Rahman Arfatur , Shakeel Kashmala , Naseem Muhammad Umair , Panyi Gyorgy , Prentis Peter J. , Norton Raymond S.
Published: October 2023

Diverse structural scaffolds have been described in peptides from sea anemones, with the ShKT domain being a common scaffold first identified in ShK toxin from Stichodactyla helianthus. ShK is a potent blocker of voltage‐gated potassium channels (KV1.x), and an analog, ShK‐186 (dalazatide), has completed Phase 1 clinical trials in plaque psoriasis. The ShKT domain has been found in numerous other species, but only a tiny fraction of ShKT domains has been characterized functionally. Despite adopting the canonical ShK fold, some ShKT peptides from sea anemones inhibit KV1.x, while others do not. Mutagenesis studies have shown that a Lys–Tyr (KY) dyad plays a key role in KV1.x blockade, although a cationic residue followed by a hydrophobic residue may also suffice. Nevertheless, ShKT peptides displaying an ShK‐like fold and containing a KY dyad do not necessarily block potassium channels, so additional criteria are needed to determine whether new ShKT peptides might show activity against potassium channels. In this study, we used a combination of NMR and molecular dynamics (MD) simulations to assess the potential activity of a new ShKT peptide. We determined the structure of ShKT‐Ts1, from the sea anemone Telmatactis stephensoni, examined its tissue localization, and investigated its activity against a range of ion channels. As ShKT‐Ts1 showed no activity against KV1.x channels, we used MD simulations to investigate whether solvent exposure of the dyad residues may be informative in rationalizing and potentially predicting the ability of ShKT peptides to block KV1.x channels. We show that either a buried dyad that does not become exposed during MD simulations, or a partially exposed dyad that becomes buried during MD simulations, correlates with weak or absent activity against KV1.x channels. Therefore, structure determination coupled with MD simulations, may be used to predict whether new sequences belonging to the ShKT family may act as potassium channel blockers.
Assessment of protein–ligand complexes in CASP15
Authors: Robin Xavier , Studer Gabriel , Durairaj Janani , Eberhardt Jerome , Schwede Torsten , Walters W. Patrick
Published: October 2023

CASP15 introduced a new category, ligand prediction, where participants were provided with a protein or nucleic acid sequence, SMILES line notation, and stoichiometry for ligands and tasked with generating computational models for the three‐dimensional structure of the corresponding protein–ligand complex. These models were subsequently compared with experimental structures determined by x‐ray crystallography or cryoEM. To assess these predictions, two novel scores were developed. The Binding‐Site Superposed, Symmetry‐Corrected Pose Root Mean Square Deviation (BiSyRMSD) evaluated the absolute deviations of the models from the experimental structures. At the same time, the Local Distance Difference Test for Protein–Ligand Interactions (lDDT‐PLI) assessed the ability of models to reproduce the protein–ligand interactions in the experimental structures. The ligands evaluated in this challenge range from single‐atom ions to large flexible organic molecules. More than 1800 submissions were evaluated for their ability to predict 23 different protein–ligand complexes. Overall, the best models could faithfully reproduce the geometries of more than half of the prediction targets. The ligands' size and flexibility were the primary factors influencing the predictions' quality. Small ions and organic molecules with limited flexibility were predicted with high fidelity, while reproducing the binding poses of larger, flexible ligands proved more challenging.
Case–control matching‐guided exposure‐efficacy relationship for avelumab in patients with urothelial carcinoma
Authors: Soltantabar Pooneh , Alhadab Ali , Hibma Jennifer , Roychoudhury Satrajit , Wang Diane D. , Bello Carlo , Elmeliegy Mohamed
Published: October 2023

Exposure‐response (E‐R) analyses are an integral component of understanding the benefit/risk profile of novel oncology therapeutics. These analyses are typically conducted using data from the treatment arm to characterize the relationship between drug exposure (low vs. high) and efficacy or safety outcomes. For example, outcomes of patients with lower exposure in the treatment arm (e.g., Q1) might be compared to outcomes of those with higher drug exposure (Q2, Q3, and Q4). Outcomes from the lowest exposure quartile may be also compared to the control arm to evaluate whether the Q1 subgroup derived clinical benefit. However, the sample size and the distribution of patient baseline characteristics and disease risk factors are not balanced in such a comparison (Q1 vs. control), which may bias the analysis and causal interpretation of clinical benefit in the Q1 subgroup. Herein, we report the use of case–control matching to account for this bias and better understand the E‐R relationship for avelumab in urothelial carcinoma, a PD‐L1 inhibitor approved for the treatment of several cancers. Data from JAVELIN‐100 was utilized which is a phase III study of avelumab in first‐line maintenance treatment in patients with urothelial carcinoma; this clinical study demonstrated superiority of avelumab versus best‐supportive care leading to approval in the United States, Europe, and other countries. A post hoc case‐control matching method was implemented to compare the efficacy outcome between Q1 avelumab subgroup and matched patients extracted from the control arm with similar baseline characteristics, which showed a clinically relevant difference in overall survival in favor of the Q1 avelumab subgroup. This analysis demonstrates the importance of accounting for imbalance in important baseline covariates when comparing efficacy outcomes between subgroups within the treatment arm versus the control arm.
Analog Quantum Bit Based on Pancharatnam‐Berry Phase Metasurfaces
Authors: Chen Long , You Jian Wei , Gu Ze , Ma Qian , Cui Tie Jun
Published: October 2023

The emergence of information metamaterials has spurred significant advances in the field of information sciences. However, the current studies are predominantly focused on classical bits as the fundamental information units, and the classical bit can only be located at two poles of Bloch sphere, resulting in limited information capacity. To break such limit, quantum bits (qubits) offer a promising solution since they have superposition states anywhere on the Bloch sphere. Here, a Pancharatnam‐Berry (PB) phase metasurface is used to emulate the qubits. Firstly, it proposes a theoretical concept of analog quantum bit and develops its mathematical and geometrical representations. Subsequently, a meta‐atom is designed as a physical platform to implement the concept of analog qubits. By manipulating the geometric configuration of the proposed meta‐atom, it achieves arbitrary superpositions of polarization states. A PB phase metasurface is experimentally fabricated to validate that the proposed analog qubit can be used to emulate the quantum bit in terms of both mathematical and geometrical representations. This work not only provides a theoretical foundation to go beyond the information limit of classical bits but also develops a feasible physics platform to investigate quantum information metasurfaces, which would complement and revolutionize classical information science.
Prominin‐1 expression in the testis/epididymis and fertility
Authors: Fargeas Christine A. , Jászai József , Corbeil Denis
Published: October 2023

The contribution of Prominin‐1 (aka CD133) to male fertility has recently been (re)investigated, with contradictory results. Early findings, essential for deciphering its role, have unfortunately been neglected. Here, the authors present what is currently known about its expression in the male reproductive system of rodents and men so that its involvement in male fertility can be re‐examined and discussed in the light of these elements.
In situ skid estimation for mobile robots in outdoor environments
Authors: Nourizadeh Payam , McFadden Fiona J. Stevens , Browne Will N.
Published: October 2023

Skidding is a surface hazard for mobile robots' navigation and traction control systems when operating in outdoor environments and uneven terrains due to the wheel–terrain interaction. It could lead to large trajectory tracking errors, losing the robot's controllability, and mission failure occurring. Despite research in this field, the development of a real‐world feasible in situ skid estimation system with the capability of operating in harsh and unforeseen environments using low‐cost/power and ease of integrating sensors is still an open problem in terramechanics. This paper presents a novel velocity‐based definition for skidding that enables a real‐world feasible estimation for the mobile robot's undesired skidding at the vehicle‐level in outdoor environments. The proposed technique estimates the undesired skidding using a combination of two proprioceptive sensors (e.g., inertial measurement unit and wheel encoder) and deep learning. The practicality of a velocity‐based definition and the performance of the proposed undesired skid estimation technique are evaluated experimentally in various outdoor terrains. The results show that the proposed technique performs with less than 11.79 mm/s mean absolute error and estimates the direction of undesired skidding with approximately 98% accuracy.
Temperature‐Sensitive Properties and Mechanism of Smart Magnetic Fluids Modified with Cellulose Derivatives
Authors: Yang Shuying , Jiang Hui , Duan Le , Zuo Kaixuan , Urujeni Gisèle Ineza , Li DuoDuo , Yao Yuyang , Xiao Deli
Published: October 2023

Combining magnetic materials with environmentally sensitive polymers to develop intelligent magnetic fluids that respond to external stimuli has become a new research hotspot. At present, the bottlenecks in the development of temperature‐sensitive materials are the complex composition, and its properties in different laboratories vary greatly. Moreover, despite extensive research on magnetic fluids, there remains a dearth of systematic investigation into temperature‐sensitive intelligent magnetic fluids. In this study, we utilized a UV‐visible spectrophotometer to measure the change in transmittance of different magnetic fluid solutions with temperature variation. We systematically investigated the effects of the magnetic fluid dispersion medium, size and concentration of magnetic nanoparticles, type and viscosity of cellulose on the temperature sensitivity of the magnetic fluid. We found that compared with Hydroxypropyl Methyl Cellulose (HPMC) (type I), HPMC (type II) modified magnetic fluid has better stability and a higher phase transition temperature. Moreover, with the increase of the concentration of magnetic fluid, the phase transition temperature is higher. In addition, the lower the viscosity of HPMC‐modified magnetic fluid, the better the stability and the higher the phase transition temperature. We also studied the mechanism of temperature sensitivity, and the results showed that hydrogen bond interactions play an important role. This research will facilitate the use of temperature‐sensitive smart magnetic fluids for biomedical application.
Synergistic Effect of Selenium Dioxide for Better Photocatalytic Performance of Conventional Semiconductors Distributed into Mesoporous SBA‐15
Authors: Ranjbar‐Niavol Neda , Zanjanchi Mohammad Ali , Farjood Mehrdad
Published: October 2023

The mesoporous SBA‐15 was synthesized in acidic conditions by hydrothermal method using Pluronic surfactant P123. A combination of SeO2, TiO2, and CuO was loaded in SBA‐15 in pairs or singly. Synthesized SBA‐15 and some loaded mesoporous materials were characterized using several standard techniques. The efficiency of the synthesized photocatalysts was verified for the decomposition of two different dyes (methylene blue (MB) and methyl green (MG)) under ultraviolet and visible light radiation. The results show that the synthesized photocatalyst based on SBA‐15 with 5 % by weight of TiO2 and 5 % by weight of SeO2 has better performance (about 98 % of MB or MG were degraded within 120 min under UV radiation). Also, the photocatalyst with 5 % by weight of SeO2 and 5 % by weight of CuO shows a good performance for the degradation of the dyes under visible irradiation in the presence of H2O2 (complete elimination of MB and MG within 150 and 75 min, respectively). The scavenging test shows that superoxide has a governing role for the degradation of the dyes. The photocatalysts are reusable and they could preserve more than 74 % of the efficiency following 4 times of consecutive use for the degradation of the dyes.
Graphene‐Based Nano Materials: Biomedical Applications
Authors: Jakhar Ajay , Sharma Jyoti , Sharma Sharad , Krishan Sharma Lavanya
Published: October 2023

Graphene is a single layered two‐dimensional structure of graphite and it has been a flaming topic of research due to its remarkable properties. The efficiency of graphene‐based materials is exploited in many spheres of life ranging from biosensing, targeted drug delivery, bio‐imaging, quantum physics, transportation, energy storage devices, faster electronics, and many more. Graphene is made of a monolayer of sp2carbon atoms organized in a hexagonal pattern with a C−C bond length of 1.42 A. Graphene has attracted interest in the development of electrochemical sensors and biosensors due to its excellent electrical conductivity, significant surface area, and high electron transfer potential. Because of these exclusive characteristics, it has also become a suitable contender for extensive biomedical uses that favors the differentiation of human mesenchymal stem cells (MSC) into bone cells and inhibit proliferation of cells, fluorescence quenching, drug/gene delivery, tissue engineering and antitumor treatments. In last ten years, notable research has been conducted to explore its biomedical applications. Encouraged by its numerous successful integrations into the biomedical fields, the up‐to‐date developments of graphene applications in various dimensions of biomedical field such as biosensors, gene and drug delivery, photo‐thermal therapy, bio‐imaging and tissue engineering are summarized here.
“Why am I here?”: A phenomenological exploration of first‐generation college student experiences in STEM majors within a predominantly white institution
Authors: Marco‐Bujosa Lisa M. , Baker Lauren , Malott Krista M.
Published: October 2023

First‐generation college students (FGCSs) are a growing population in undergraduate education. Research on FGCS primarily focuses on the challenges and barriers they encounter in college. While important, this literature offers a limited view of FGCS as learners. Moreover, minimal literature has examined these students' lived experiences within sciences, technology, engineering, and mathematics (STEM). This study explores the learning experiences of FGCS (N = 17) in undergraduate STEM programs at a mid‐sized, private, predominantly white institution. Guided by the frameworks of intersectionality and social cognitive career theory, the researchers utilized a qualitative, phenomenological research methodology to hear the perspectives of FGCS to and to identify problematic higher educational structures in STEM. Findings point to an elitist stance underlying STEM programs based in general disciplinary norms that restricted FGCS access to STEM majors and careers across social, academic, and professional elements of the academic experience. FGCS who were multiply minoritized based upon race, gender, and social class experienced the compounding of marginalization, and academic success and persistence came at a personal cost. Students also reported relying predominantly on personal strengths and motivations to overcome elitism in STEM rather than on institutional supports. Findings also highlight the variation in the first‐generation experience and identify the unique barriers FGCS encounter within STEM fields. Implications for dismantling inequitable structures for higher education in STEM attending to the social, academic, and professional inclusion of FGCS.
An efficient acoustic classifier for high‐priority avian species in the southern Great Plains using convolutional neural networks
Authors: Wolfe Brandon , Proctor Mike D. , Nolan Victoria , Webb Stephen L.
Published: October 2023

Passive acoustic monitoring is a valuable ecological and conservation tool that allows researchers to collect data from vocal species across large geographic areas and temporal spans. Grassland bird populations, many of which are indicators of ecosystem health, have experienced precipitous declines over the past several decades. Acoustic monitoring of grassland bird populations provides opportunities to monitor declines and focus conservation practices, yet the ability to identify species efficiently and accurately from acoustic data is challenging. Therefore, development of automated classifiers such as convolutional neural networks (CNNs) are at the forefront of streamlining detection and identification of individual species. Here, we present a CNN classifier for 5 key grassland bird species across southcentral Oklahoma, a part of the southern Great Plains: northern bobwhite (Colinus virginianus), painted bunting (Passerina ciris), dickcissel (Spiza americana), eastern meadowlark (Sturnella magna), and Bell's vireo (Vireo bellii). We compiled a high‐quality training dataset consisting of 6,933 calls, built semiautonomously using template matching that can be expanded easily to any bird species of interest. Our trained multilabel CNN achieved a high level of classification accuracy (≥98%) for the 5 species using the library of test calls and field recordings played using a programmable game caller. The ability to conduct acoustic wildlife surveys across large spatial extents will allow for more efficient monitoring of wildlife to determine key population parameters and trends and effects of biotic and abiotic factors (e.g., vegetation, disturbance, weather) on these key species.
Double Kerr-Schild spacetimes and the Newman-Penrose map
Authors: Farnsworth Kara , Graesser Michael L. , Herczeg Gabriel
Published: October 2023

Abstract

The Newman-Penrose map, which is closely related to the classical double copy, associates certain exact solutions of Einstein’s equations with self-dual solutions of the vacuum Maxwell equations. Here we initiate an extension of the Newman-Penrose map to a broader class of spacetimes. As an example, we apply principles from the Newman-Penrose map to associate a self-dual gauge field to the Kerr-Taub-NUT-(A)dS spacetime and we show that the result agrees with previously studied examples of classical double copies. The corresponding field strength exhibits a discrete electric-magnetic duality that is distinct from its (Hodge star) self-dual property.
On s-confining SUSY-QCD with anomaly mediation
Authors: de Lima Carlos Henrique , Stolarski Daniel
Published: October 2023

Abstract

In this work, we present a comprehensive study of the phase diagram of supersymmetric QCD with Nf = Nc + 1 flavors perturbed by Anomaly Mediated Supersymmetry Breaking (AMSB). We extend the previous analyses on s-confining ASQCD theories in three different directions. We show that the existence of the QCD-like vacuum is independent of the size of the SUSY breaking parameter. We further expand the analysis of these models by including two and three-loop contributions to investigate the robustness and limitations of the results. Finally, we include the leading effect of higher-order Kähler terms to investigate the stability of the phase diagram as we approach the confining energy scale. The analysis with higher order Kähler terms is also extended for Nc = 2 for which AMSB alone gives inconclusive results.
2-index chiral gauge theories
Authors: Anber Mohamed M. , Chan Samson Y. L.
Published: October 2023

Abstract

We undertake a systematic study of the 4-dimensional SU(N) 2-index chiral gauge theories and investigate their faithful global symmetries and dynamics. These are a finite set of theories with fermions in the 2-index symmetric and anti-symmetric representations, with no fundamentals, and they do not admit a large-N limit. We employ a combination of perturbative and nonperturbative methods, enabling us to constrain their infrared (IR) phases. Specifically, we leverage the ’t Hooft anomalies associated with continuous and discrete groups to eliminate a few scenarios. In some cases, the anomalies rule out the possibility of fermion composites. In other cases, the interplay between the continuous and discrete anomalies leads to multiple higher-order condensates, which inevitably form to match the anomalies. Further, we pinpoint the most probable symmetry-breaking patterns by searching for condensates that match the full set of anomalies resulting in the smallest number of IR degrees of freedom. Higher-loop β-function analysis suggests that a few theories may flow to a conformal fixed point.
JASON in Europe: Contestation and the Physicists’ Dilemma about the Vietnam War
Authors: Ienna Gerardo , Turchetti Simone
Published: October 2023

This article examines the contestation that in the summer of 1972 disrupted workshops in Western Europe featuring renowned physicists affiliated to the top-secret JASON advisory group. Set up by the US Department of Defense research division, JASON was responsible for outlining new bombing strategies in the context of the Vietnam War. Some of the physicists involved in the protest had contributed instead to the International War Crimes (Russell) Tribunal, gathering evidence in Indochina on the allegedly genocidal character of the US bombing. In reconstructing the history of the contestation, this article contends that the conflict was an opportunity for advertising diverging political stances in the rebellious atmosphere of early 1970s, as much as to convey competing views about the physicists’ influence on global affairs. In particular, while JASON members boasted that their advisory roles stifled bellicose approaches, the protesters recalled the merits of independent inquiry and advocacy “from below” the elitist sphere of government advice, describing these as a better way to advance principles of global social justice.
Evaluation of chemical constituents of Rooibos (Aspalathus linearis) and Honeybush (Cyclopia intermedia) as adenosine A1/A2A receptor ligands
Authors: Gouws Liezel , Janse van Rensburg Helena D. , Terre’Blanche Gisella , Van der Walt Mietha M.
Published: October 2023

Rooibos (Aspalathus linearis) and Honeybush (Cyclopia intermedia) are popular tisanes in South Africa and are of growing interest due to the wide variety of flavonoids and other phytochemicals they contain. Despite their history as herbal teas and traditional medicines, the chemical constituents of these tisanes have yet to be studied for their effects on adenosine receptors. A series of 30 commercially available chemical constituents of Rooibos and Honeybush were investigated via radioligand binding studies to determine their adenosine A1 and A2A receptor affinity at both rat and human subtypes in order to establish structure-activity relationships and identify novel adenosine receptor ligands. In addition, in silico evaluations of the 30 test compounds were also performed to predict their physiochemical and pharmacokinetic properties. The most promising chemical constituent was kaempferol (28) which showed sub-micromolar affinity towards the rat A1 subtype (rA1Ki = 0.7287 μM; hA1Ki = 9.88 µM) and acted as an antagonist toward adenosine rA1 receptors. Additionally, quercetin (2), chrysoeriol (8), luteolin (9), eriodyctiol (12), and naringenin (27) also showed adenosine A1 and/or A2A receptor affinity. It was observed that a flavonol scaffold is preferred to flavone and flavanone scaffolds, and within the flavonols, C4’-OH substitution on ring B is preferred to C3’,4’-diOH substitution. These phytochemicals, specifically kaempferol (28), may be considered lead-like and valuable in designing novel ligands, based on in vitro and in silico evaluation.
Prävalenz von Schleimhautläsionen bei Durchführung der transnasalen endoskopischen Dysphagiediagnostik und angelegter Nasogastralsonde
Authors: Heise Kira-Milena , Miller Simone , Ptok Martin , Jungheim Michael
Published: October 2023

Hintergrund

Zur Einschätzung des Penetrations- oder Aspirationsrisikos bei Dysphagien hat sich unter anderem die flexible endoskopische Evaluation des Schluckakts (FEES) etabliert. Sie gilt als komplikationsarmes Verfahren, ist jedoch bei angelegter Nasogastralsonde (NGS) erschwert durchführbar und könnte mit einer höheren Rate akzidenteller Schleimhautläsionen einhergehen.

Zielsetzung

In dieser Studie sollte ermittelt werden, ob eine erhöhte Prävalenz von Schleimhautläsionen vorliegt, wenn die FEES bei liegender NGS und damit unter erschwerten Untersuchungsbedingungen durchgeführt wird. Präexistente Läsionen sollten ebenfalls erfasst werden.

Methodik

In einer retrospektiven, monozentrischen Studie wurden insgesamt 918 videodokumentierte FEES-Untersuchungen, die zu diagnostischen Zwecken bei stationären Patient*innen mit angelegter Nasogastralsonde von Januar 2014 bis März 2019 an einer Universitätsklinik durchgeführt wurden, ausgewertet. Erfasst wurden Anzahl und Ausprägungen von Schleimhautläsionen.

Ergebnisse

In keinem der hier analysierten Fälle trat eine endoskopiebedingte Verletzung auf. Bei 48,6 % der analysierten Endoskopien konnten jedoch präexistente Läsionen in Nase und/oder Nasopharynx festgestellt werden, die häufig als Mehrfachverletzungen vorlagen.

Schlussfolgerung

Die Ergebnisse der Studie zeigen, dass die FEES hinsichtlich der Gefahr einer akzidentellen Schleimhautverletzung auch bei in situ befindlicher NGS eine sichere und risikoarme Untersuchungsmethode ist. Bemerkenswert ist jedoch die sehr hohe Zahl präexistenter Schleimhautläsionen, die mit hoher Wahrscheinlichkeit in Zusammenhang mit dem zuvor erfolgten Legen einer NGS stehen. Die Häufigkeit präexistenter Läsionen lässt es ratsam erscheinen, Strategien zur Verletzungsminimierung beim Legen von Nasogastralsonden zu entwickeln.
Characterisation of HNF1A variants in paediatric diabetes in Norway using functional and clinical investigations to unmask phenotype and monogenic diabetes
Authors: Svalastoga Pernille , Kaci Alba , Molnes Janne , Solheim Marie H. , Johansson Bente B. , Krogvold Lars , Skrivarhaug Torild , Valen Eivind , Johansson Stefan , Molven Anders , Sagen Jørn V. , Søfteland Eirik , Bjørkhaug Lise , Tjora Erling , Aukrust Ingvild , Njølstad Pål R.
Published: October 2023

Aims/hypothesis

Correctly diagnosing MODY is important, as individuals with this diagnosis can discontinue insulin injections; however, many people are misdiagnosed. We aimed to develop a robust approach for determining the pathogenicity of variants of uncertain significance in hepatocyte nuclear factor-1 alpha (HNF1A)-MODY and to obtain an accurate estimate of the prevalence of HNF1A-MODY in paediatric cases of diabetes.

Methods

We extended our previous screening of the Norwegian Childhood Diabetes Registry by 830 additional samples and comprehensively genotyped HNF1A variants in autoantibody-negative participants using next-generation sequencing. Carriers of pathogenic variants were treated by local healthcare providers, and participants with novel likely pathogenic variants and variants of uncertain significance were enrolled in an investigator-initiated, non-randomised, open-label pilot study (ClinicalTrials.gov registration no. NCT04239586). To identify variants associated with HNF1A-MODY, we functionally characterised their pathogenicity and assessed the carriers’ phenotype and treatment response to sulfonylurea.

Results

In total, 615 autoantibody-negative participants among 4712 cases of paediatric diabetes underwent genetic sequencing, revealing 19 with HNF1A variants. We identified nine carriers with novel variants classified as variants of uncertain significance or likely to be pathogenic, while the remaining ten participants carried five pathogenic variants previously reported. Of the nine carriers with novel variants, six responded favourably to sulfonylurea. Functional investigations revealed their variants to be dysfunctional and demonstrated a correlation with the resulting phenotype, providing evidence for reclassifying these variants as pathogenic.

Conclusions/interpretation

Based on this robust classification, we estimate that the prevalence of HNF1A-MODY is 0.3% in paediatric diabetes. Clinical phenotyping is challenging and functional investigations provide a strong complementary line of evidence. We demonstrate here that combining clinical phenotyping with functional protein studies provides a powerful tool to obtain a precise diagnosis of HNF1A-MODY.

Graphical Abstract
Optimal conspicuity of pancreatic ductal adenocarcinoma in virtual monochromatic imaging reconstructions on a photon-counting detector CT: comparison to conventional MDCT
Authors: Decker Josua A. , Becker Judith , Härting Mark , Jehs Bertram , Risch Franka , Canalini Luca , Wollny Claudia , Scheurig-Muenkler Christian , Kroencke Thomas , Schwarz Florian , Bette Stefanie
Published: October 2023

Purpose

To analyze the conspicuity of pancreatic ductal adenocarcinoma (PDAC) in virtual monoenergetic images (VMI) on a novel photon-counting detector CT (PCD-CT) in comparison to energy-integrating CT (EID-CT).

Methods

Inclusion criteria comprised initial diagnosis of PDAC (reference standard: histopathological analysis) and standardized contrast-enhanced CT imaging either on an EID-CT or a PCD-CT. Patients were excluded due to different histopathological diagnosis or missing tumor delineation on CT. On the PCD-CT, 40–190 keV VMI reconstructions were generated. Image noise, tumor-to-pancreas ratio (TPR) and contrast-to-noise ratio (CNR) were analyzed by ROI-based measurements in arterial and portal venous contrast phase. Two board-certified radiologist evaluated image quality and tumor delineation at both, EID-CT and PCD-CT (40 and 70 keV).

Results

Thirty-eight patients (mean age 70.4 years ± 10.3 [range 45–91], 27 males; PCD-CT: n=19, EID-CT: n=19) were retrospectively included. On the PCD-CT, tumor conspicuity (reflected by low TPR and high CNR) was significantly improved at low-energy VMI series (≤ 70 keV compared to > 70 keV), both in arterial and in portal venous contrast phase (P < 0.001), reaching the maximum at 40 keV. Comparison between PCD-CT and EID-CT showed significantly higher CNR on the PCD-CT in portal venous contrast phase at < 70 keV (P < 0.016). On the PCD-CT, tumor conspicuity was improved in portal venous contrast phase compared to arterial contrast phase especially at the lower end of the VMI spectrum (≤ 70 keV). Qualitative analysis revealed that tumor delineation is improved in 40 keV reconstructions compared to 70 keV reconstructions on a PCD-CT.

Conclusion

PCD-CT VMI reconstructions (≤ 70 keV) showed significantly improved conspicuity of PDAC in quantitative and qualitative analysis in both, arterial and portal venous contrast phase, compared to EID-CT, which may be important for early detection of tumor tissue in clinical routine. Tumor delineation was superior in portal venous contrast phase compared to arterial contrast phase.
Heisenberg Spin Exchange Between Nitroxide Probes Diffusing in a Percolation Network
Authors: Lawton Jamie S. , Budil David E.
Published: October 2023

Heisenberg spin exchange between nitroxide (Tempone) spin probes has been measured as a function of concentration in the aqueous phase of the hydrated ion exchange membrane Nafion 117. The observed fast-motional electron paramagnetic resonance spectra were analyzed in terms of the stochastic Liouville equation lineshape calculation of Freed and coworkers and the “new paradigm” for interpreting spin exchange effects proposed by Salikhov. Differences between the effective spin exchange measured from the spectrum by these methods are presented and compared, and indicate that dipolar interactions make a significant contribution to spin exchange in this system. In acidic Nafion membranes, the spin probes are deactivated over time, allowing simultaneous measurement of the decay kinetics and spin exchange as a function of paramagnetic probe concentration. Both these processes deviate from the behavior that would be expected from classical chemical kinetics in isotropic media. The results are discussed in terms of currently available models for diffusion and reaction in a percolation network.
Locating $$\gamma$$-ray sources on the celestial sphere via modal clustering
Authors: Montin Anna , Brazzale Alessandra R. , Menardi Giovanna , Sottosanti Andrea
Published: October 2023

Sky surveys represent the fundamental data basis for detecting and locating as yet undiscovered celestial objects. Since 2008, the Fermi LAT Collaboration has catalogued thousands of $$\gamma$$
γ
-ray sources with the aim of extending our knowledge of the highly energetic physical mechanisms and processes that lie at the core of our Universe. In this article, we present a nonparametric clustering algorithm which identifies high-energy astronomical sources using the spatial information of the $$\gamma$$
γ
-ray photons detected by the large area telescope onboard the Fermi spacecraft. In particular, the sources are identified using a von Mises–Fisher kernel estimate of the photon count density on the unit sphere via an adjustment of the mean-shift algorithm which accounts for the directional nature of the collected data and the need of local smoothing. This choice entails a number of desirable benefits. It allows us to bypass the difficulties inherent on the borders of any projection of the photon directions onto a 2-dimensional plane, while guaranteeing high flexibility. The smoothing parameter is chosen adaptively, by combining scientific input with optimal selection guidelines, as known from the literature. Using statistical tools from hypothesis testing and classification, we furthermore present an automatic way to skim off sound candidate sources from the $$\gamma$$
γ
-ray emitting diffuse background and to quantify their significance. We calibrate and test our algorithm on simulated count maps provided by the Fermi LAT Collaboration.
Stiffness influence on particle separation in polydimethylsiloxane-based deterministic lateral displacement devices
Authors: Marhenke Julius , Dirnecker Tobias , Vogel Nicolas , Rommel Mathias
Published: October 2023

Polydimethylsiloxane (PDMS) is a popular material to rapidly manufacture microfluidic deterministic lateral displacement (DLD) devices for particle separation. However, manufacturing and operation challenges are encountered with decreasing device dimensions required to separate submicron particles. The smaller dimensions, notably, cause high hydraulic resistance, resulting in significant pressure even at relatively low throughputs. This high pressure can lead to PDMS deformation, which, in turn, influences the device performance. These effects may often be overlooked in the design and operation of devices but provide a systematic source of error and inaccuracies. This study focuses in detail on these effects and investigates pillar deformation in detail. Subsequently, we discuss a potential solution to this deformation using thermal annealing to stiffen the PDMS. We evaluate the influence of stiffness on the separation performance at elevated sample flow rates with submicron particles (0.45 and 0.97 µm diameter). An excellent separation performance at high throughput is successfully maintained in stiffer PDMS-based DLD devices, while the conventional devices showed decreased separation performance. However, the increased propensity for delamination constrains the maximal applicable throughput in stiffer devices. PDMS deformation measurements and numerical simulations are combined to derive an iterative model for calculating pressure distribution and PDMS deformation. Finally, the observed separation characteristics and encountered throughput constraints are explained with the iterative model. The results in this study underline the importance of considering pressure-induced effects for PDMS-based DLD devices, provide a potential mitigation of this effect, and introduce an approach for estimating pressure-induced deformation.
Conservation genomics of Dioon holmgrenii (Zamiaceae) reveals a history of range expansion, fragmentation, and isolation of populations
Authors: Dorsey Brian L. , Salas-Morales Silva H. , Gregory Timothy J.
Published: October 2023

Many Cycad species may not survive the current extinction crisis, despite belonging to the oldest living seed plant lineage. Conservation of endangered and threatened species will require a combination of in situ and ex situ programs, both of which will benefit from better knowledge of species’ population genetic structure, as will assessments of threatened status. Here we develop a cost-effective method of obtaining population-level genomic data from across the range of the Mexican cycad, Dioon holmgreni, and use these data to characterize the genetic structure and diversity of the species. We also reconstruct aspects of the demographic history of the species and evaluate the taxonomic cohesion of populations across the range using genomic and morphological data. We find that D. holmgrenii harbors moderate genetic diversity across genetically and geographically isolated populations that each possess a substantial percentage of private alleles. We further find that the history of this species likely includes a widespread range expansion followed by fragmentation due to population contraction. These results argue for conservation of all populations and their unique alleles but also suggest an unexpected ability of this species to maintain genetic diversity despite dramatic reductions in population size.
Phase 1/1b open-label, dose-escalation study of fruquintinib in patients with advanced solid tumors in the United States
Authors: Wang-Gillam Andrea , Schelman William , Ukrainskyj Stacey , Chien Caly , Gonzalez Martha , Yang Zhao , Kania Marek , Yeckes-Rodin Heather
Published: October 2023

This open-label, phase 1/1b study was conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of fruquintinib in United States (U.S.) patients to confirm the recommended phase 2 dose (RP2D) established in China. Patients with advanced solid tumors who had progressed on approved systemic therapy, were enrolled into 2 successive dose escalation cohorts, fruquintinib 3 mg (n = 7) or 5 mg (n = 7), orally, once daily (QD), 3 weeks on and 1 week off (3/1) with a 3 + 3 design followed by a dose expansion cohort at the RP2D 5 mg dose (n = 6). PK samples were collected on Days 1, 14, and 21 (Cycle 1). One of 6 dose-limiting toxicity (DLT)-evaluable patients in the 3 mg cohort had a DLT of grade 4 hypertension; there were no DLTs in the 5 mg cohort. The RP2D was confirmed to be 5 mg QD 3/1. All 20 patients experienced a treatment-emergent adverse event; grade ≥ 3 in 5 (71.4%; 3 mg dose) and 12 (92.3%; 5 mg dose) patients. Two patients had a confirmed partial response. After single and multiple doses, median peak plasma concentrations occurred at 2 h post-dose. Steady-state was achieved after 14 days of QD dosing with systemic exposure four-fold higher than that after a single dose. Fruquintinib was well tolerated, and the safety and PK profile at the 5 mg RP2D in U.S. patients with advanced solid tumors was consistent with dose-finding studies in China. Preliminary anticancer activity was observed. This study is registered at Clinicaltrials.gov NCT03251378.
Design of a future scenarios toolkit for an ethical implementation of artificial intelligence in education
Authors: Mouta Ana , Torrecilla-Sánchez Eva María , Pinto-Llorente Ana María
Published: October 2023

In the 1970s, research on artificial intelligence in education emerged with the aim of acknowledging and accommodating the psychological aspects of the learning process. Since then, its applications have evolved and it is now used for student learning and assessment, teachers’ pedagogical practice, management of educational institutions, and lifelong learning. Nevertheless, the ethical challenges of educational programmes using these systems have not been thoroughly studied. Anchored on the theoretical frame of dialogic ethics, this paper presents a section of a participatory futures research project. The goal of the research is to develop a toolkit that educators can use to ensure a smooth and ethical transition to artificial intelligence-based education while preserving the interests of educational development. This paper emphasises the need for an informed and participatory process that involves all stakeholders and begins with an expert consultation through the Delphi method, the results of which allowed the construction of eight hypothetical futures scenarios. These scenarios provide evidence that examining the ethics of using artificial intelligence systems presents an opportunity to reflect on the ethics of education as a whole. They highlight the challenge of balancing the benefits and drawbacks of such systems, especially concerning educational goals and the interplay between diverse educational actors and personal development in educational settings. The study outcomes are intended to encourage discussions on the integration of ethical artificial intelligence in education and facilitate the continuing professional development of teachers by equipping them with scenarios that can be used as a resource for training purposes.
Competition of Rhyzopertha dominica and Sitophilus oryzae on six sorghum varieties
Authors: Agrafioti Paraskevi , Arthur Frank H. , Athanassiou Christos G.
Published: October 2023

We tested the effect of simultaneous infestation by adults of the lesser grain borer, Rhyzopertha dominica (F.) and the rice weevil, Sitophilus oryzae (L.) on six sorghum varieties. For this purpose, vials containing sorghum and either each species alone or both species were placed at 30 °C and 65% relative humidity. After ten days, all parental adults were removed and the vials were returned to the same conditions. Five weeks later the vials were emptied, to record adult emergence, the percentage of insect damaged kernels (IDK), and frass weight. Our results indicated that progeny production capacity for both species was not affected by the simultaneous presence of R. dominica and S. oryzae, and that adult emergence was more of a variety- mediated parameter. Both species had previously shown similar preferences towards specific sorghum varieties. IDK and frass were higher in vials containing R. dominica alone rather than S. oryzae alone, but these indicators were not always related to progeny production. Specifically, the most and the least frass production was noted on Sumac and PE sorghum varieties for both species, respectively. When the two species were placed together in the same vial, the most frass production was noted in the Non-Waxy Burgundy and Sumac varieties. Our results suggest that varietal resistance in sorghum could be utilized to help reduce post-harvest infestations by S. oryzae and R. dominica.
Barriers and Facilitators to Behavioral Healthcare for Women Veterans: a Mixed-Methods Analysis of the Current Landscape
Authors: Fitzke Reagan E. , Bouskill Kathryn E. , Sedano Angeles , Tran Denise D. , Saba Shaddy K. , Buch Keegan , Hummer Justin F. , Davis Jordan P. , Pedersen Eric R.
Published: October 2023

Women veterans have historically faced barriers to behavioral health treatment, particularly through the VA. In conjunction, there have been changes in behavioral healthcare delivery resulting from efforts to improve care for women veterans and the COVID-19 pandemic (e.g., widespread telehealth implementation). The current study draws on a quantitative and qualitative study centering current perspectives of women veterans in their choices to seek or not seek behavioral healthcare in VA and non-VA settings through interviewing 18 women recruited from a larger survey study on veteran behavioral health (n = 83 women, n = 882 men) on their experiences with behavioral health care access and satisfaction, including barriers and facilitators to seeking care. Quantitative findings are descriptively reported from the larger study, which outlined screening for behavioral health problems, behavioral health utilization, treatment modality preferences, and barriers/facilitators to care. While women in the survey sample screened for various behavioral health disorders, rates of treatment seeking remained relatively low. Women reported positive and negative experiences with telehealth and endorsed many barriers to treatment seeking in interviews not captured by survey findings, including lack of women-specific care (e.g., care for military sexual trauma, women-only groups), reports of stranger harassment at the VA, and lack of female providers. Women veterans continue to face barriers to behavioral healthcare; however, ongoing efforts to improve care access and quality, including the implementation of telehealth, show promise in reducing these obstacles. Continued efforts are needed to ensure diverse treatment modalities continue to reach women veterans as this population grows.