bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Analysis of Mitochondrial RNA in Living Cells with a Dual‐Color Imaging System
Authors: Chen Zhiyan , Zeng Su , Qian Linghui
Published: May 2023

Accurate quantification and dynamic expression profiling of mitochondrial RNA (mtRNA for short) are critical for illustrating their cellular functions. However, there lack methods for precise detection of mtRNA in situ due to the delivery restrictions and complicated cellular interferences. Herein, a dual‐color imaging system featured with signal amplification and normalization capability for quantitative analysis of specific mtRNA is established. As a proof‐of‐concept example, an enzyme‐free hairpin DNA cascade amplifier fine‐tailored to specifically recognize mtRNA encoding NADH dehydrogenase subunit 6 (ND6) is employed as the signal output module and integrated into the biodegradable mitochondria‐targeting black phosphorus nanosheet (BP‐PEI‐TPP) to monitor spatial‐temporal dynamics of ND6 mtRNA. An internal reference module targeting β‐actin mRNA is sent to the cytoplasm via BP‐PEI for signal normalization, facilitating mtRNA quantification inside living cells with a degree of specificity and sensitivity as high as reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). With negligible cytotoxicity, this noninvasive “RT‐qPCR mimic” can accurately indicate target mtRNA levels across different cells, providing a new strategy for precise analysis of subcellular RNAs in living systems.
Dual Electronic Modulations on NiFeV Hydroxide@FeOx Boost Electrochemical Overall Water Splitting
Authors: Yao Haibin , Le Fuhe , Jia Wei , Cao Yali , Sheng Rui , Lu Zhenjiang , Chen Xianhao , Jia Dianzeng
Published: May 2023

Nickel‐iron based hydroxides have been proven to be excellent oxygen evolution reaction (OER) electrocatalysts, whereas they are inactive toward hydrogen evolution reaction (HER), which severely limits their large‐scale applications in electrochemical water splitting. Herein, a heterostructure consisted of NiFeV hydroxide and iron oxide supported on iron foam (NiFeV@FeOx/IF) has been designed as a highly efficient bifunctional (OER and HER) electrocatalyst. The V doping and intimate contact between NiFeV hydroxide and FeOx not only improve the entire electrical conductivity of the catalyst but also afford more high‐valence Ni which serves as active sites for OER. Meanwhile, the introduction of V and FeOx reduces the electron density on lattice oxygen, which greatly facilitates desorption of Hads. All of these endow the NiFeV@FeOx/IF with exceptionally low overpotentials of 218 and 105 mV to achieve a current density of 100 mA cm−2 for OER and HER, respectively. More impressively, the electrolyzer requires an ultra‐low cell voltage of 1.57 V to achieve 100 mA cm−2 and displays superior electrochemical stability for 180 h, which outperforms commercial RuO2||Pt/C and most of the representative catalysts reported to date. This work provides a unique route for developing high‐efficiency electrocatalyst for overall water splitting.
Moiré‐Pattern Modulated Electronic Structures of GaSe/HOPG Heterostructure
Authors: Li Wenhui , Gao Qian , Wang Yu , Cheng Peng , Zhang Yi‐Qi , Feng Baojie , Hu Zhenpeng , Wu Kehui , Chen Lan
Published: May 2023

Conventional two‐dimensional electron gas (2DEG) typically occurs at the interface of semiconductor heterostructures and noble metal surfaces, but it is scarcely observed in individual 2D semiconductors. In this study, few‐layer gallium selenide (GaSe) grown on highly ordered pyrolytic graphite (HOPG) is demonstrated using scanning tunneling microscopy and spectroscopy (STM/STS), revealing that the coexistence of quantum well states (QWS) and 2DEG. The QWS are located in the valence bands and exhibit a peak feature, with the number of quantum wells being equal to the number of atomic layers. Meanwhile, the 2DEG is located in the conduction bands and exhibits a standing‐wave feature. Additionally, monolayer GaSe/HOPG heterostructures with different stacking angles (0°, 33°, 8°) form distinct moiré patterns that arise from lattice mismatch and angular rotation between adjacent atomic layers in 2D materials, which effectively modulate the electron effective mass, charge redistribution, and band gap of GaSe. Overall, this work reveals a paradigm of band engineering based on layer numbers and moiré patterns that can modulate the electronic properties of 2D materials.
Thin‐walled concrete beams with stay‐in‐place flexible formworks and integrated textile shear reinforcement
Authors: Lee Minu , Mata‐Falcón Jaime , Popescu Mariana , Kaufmann Walter
Published: May 2023

Thin‐walled textile‐reinforced concrete beams have recently emerged as a promising approach for material‐efficient design. However, the increased complexity of the formwork is a major challenge in implementing such elements for broader use in the construction industry. This study presents a novel type of stay‐in‐place flexible formworks with integrated textile reinforcement. The use of weft‐knitted textiles allows the integration of continuous high‐strength rovings as shear reinforcement and the introduction of spatial features within the fabric to guide bending‐active rods to shape the complex cross‐section geometry. The manufacturing procedure and the structural performance were investigated in an experimental campaign consisting of four concrete beams with I‐profile cross sections tested in three‐point bending, where aramid rovings were used for the shear and conventional deformed steel bars for the flexural reinforcement. The transverse reinforcement ratio proved to be essential in increasing the shear strength. Thereby, the use of digital image correlation measurements of the surface deformations allowed the direct assessment of the strains and, thus, the mechanical activation of the textile reinforcement. The full tensile capacity of all the aramid rovings crossing the governing crack could not be exploited due to the brittle material behavior, resulting in a progressive failure once the first roving reached its tensile strength. Compatibility‐based stress fields were used to predict the load‐deformation and failure behavior of the tested beams, which resulted in an excellent agreement of the ultimate loads and failure modes obtained from the model with the observations and results from the experiments.
The perception of felid welfare by zookeepers in North America and the implications for zoo managers
Authors: Ogle Brian , DeSmet Annabel
Published: May 2023

Zookeepers working with felids were asked to complete an online survey to examine their perceptions of animal welfare. A total of 121 zookeepers in an AZA‐accredited zoo completed the survey. Results from this study suggest that institutional offerings of professional development programming in animal welfare have the greatest potential to influence zookeeper perceptions of animal welfare. Participants also identified four areas of improvement for felid welfare, including 1) larger and more dynamic spaces, 2) increased attention to behavioral husbandry, 3) more unique diet presentations, and 4) the ability for the animal to remain out of the view of the public. In addition, there appear to be differences in perception between traditionally described “small cat” and “large cat” keepers in terms of the ability to deliver the Five Freedoms.
Working (and Living) During Corona Times and Implications for Planning and Mobility—The Case of Norway
Authors: Di Marino Mina , Chavoshi Seyed Hossein
Published: May 2023

The COVID-19 pandemic has relatively affected the Norwegian context and other Nordic countries (except for Sweden), considering the prudential authorities and policies adopted during the various waves of the virus. The capacity for remote working and high flexibility of working (already observed before the pandemic) have contributed to adapt to the changes. In this context, the study aims to explore the ways of working and living during the Corona Times and the implications for planning and mobility in Norway, considering the short-medium and long-term effects of the pandemic. First, the study presents an overview of the main impacts of the pandemic in the Nordic countries (such as mortality, labour market and absence from work, including the closure of workplaces), and second, it focuses on Norway, in light of the national measures. Then, the working related trends (for example, growth of demand of new working spaces and the increased number of workers in the public libraries) are discussed, as well as the major implications for our cities, such as new housing demands, commuting habits and transportation modes. Finally, an overview of the current debate within the Norwegian society shows the high interests of planners, other experts, and media in understanding the future of work, such as hybrid forms, new jobs, working remotely (but from where?).
Displaced or invisible? ALPs from B decays at Belle II
Authors: Ferber T. , Filimonova A. , Schäfer R. , Westhoff S.
Published: May 2023

Abstract

At colliders, neutral long-lived particles can be detected through displaced decay products or as missing energy. Which search strategy is better depends on the particle’s decay length just as on the detector properties. We investigate the complementarity of displaced and invisible signatures for the Belle II experiment. Focusing on axion-like particles a produced from meson decays, we present a new search strategy for two-body decays "Image missing" with missing energy "Image missing". With 50 ab−1 of data, Belle II can probe light invisible resonances with branching ratio $$ \mathcal{B} $$
B
(B+→ K+a) ≳ 10−7 and decay length cτa ≳ 1 m. For axion-like particles, we expect the sensitivity of "Image missing" to small couplings to improve by up to two orders of magnitude compared to previous searches at collider and fixed-target experiments. For sub-GeV particles, "Image missing" at Belle II and searches at beam-dump experiments are most sensitive; for heavier particles, searches for displaced vertices at Belle II, long-lived particle experiments at the LHC, and future fixed-target experiments can probe the smallest couplings.
Long-lived particle phenomenology in the 2HDM+a model
Authors: Haisch Ulrich , Schnell Luc
Published: May 2023

Abstract

Higgs decays displaced from the primary interaction vertex represent a striking experimental signature that is actively searched for by the ATLAS, CMS and LHCb collaborations. We point out that signals of this type appear in the context of the 2HDM+a model if the mixing angle θ of the two CP-odd weak spin-0 eigenstates is tiny and the dark matter (DM) sector is either decoupled or kinematically inaccessible. Utilising two suitable benchmark scenarios, we determine the constraints on the parameter space of the 2HDM+a model that are set by the existing LHC searches for long-lived particles (LLPs) in Higgs decays. We find that depending on the precise mass spectrum of the spin-0 states, mixing angles θ in the ballpark of a few 10−8 to 10−5 can be excluded based on LHC Run II data. This finding emphasises the unique role that searches for displaced signatures can play in constraining the parameter space of the 2HDM+a model. The ensuing DM phenomenology is also discussed. In particular, we show that parameter choices leading to an interesting LLP phenomenology can simultaneously explain the DM abundance observed in today’s Universe.
On SYK traversable wormhole with imperfectly correlated disorders
Authors: Nosaka Tomoki , Numasawa Tokiro
Published: May 2023

Abstract

In this paper, we study the phase structure of two Sachdev-Ye-Kitaev models (L-system and R-system) coupled by a simple interaction, with imperfectly correlated disorder. When the disorder of the two systems is perfectly correlated, $$ {J}_{i_1\cdots {i}_q}^{(L)}={J}_{i_1\cdots {i}_q}^{(R)} $$

J

i
1

⋯

i
q

L

=

J

i
1

⋯

i
q

R

, this model is known to exhibit a phase transition at a finite temperature between the two-black hole phase at high temperature and the traversable wormhole phase at low temperature. We find that, as the correlation $$ \left\langle {J}_{i_1\cdots {i}_q}^{(L)}={J}_{i_1\cdots {i}_q}^{(R)}\right\rangle $$

J

i
1

⋯

i
q

L

=

J

i
1

⋯

i
q

R

is decreased, the critical temperature becomes lower. At the same time, the transmission between the L-system and R-system in the low-temperature phase becomes more suppressed, while the chaos exponent of the whole system becomes larger. Interestingly we also observe that when the correlation is smaller than some q-dependent critical value the phase transition completely disappears in the entire parameter space. At zero temperature, the energy gap becomes larger as we decrease the correlation. We also use a generalized thermofield double state as a variational state. Interestingly, this state coincides with the ground state in the large q limit.
Oligodendrogliomas tend to infiltrate the frontal aslant tract, whereas astrocytomas tend to displace it
Authors: Landers M. J. F. , Brouwers H. B. , Kortman G. J. , Boukrab I. , De Baene W. , Rutten G. J. M.
Published: May 2023

Introduction

MR-tractography is increasingly used in neurosurgical practice to evaluate the anatomical relationships between glioma and nearby subcortical tracts. In some patients, the subcortical tracts seem displaced by the glioma, while in other patients, the subcortical tracts seem infiltrated without displacement. At this point, it is unknown whether these different patterns are related to tumor type. The aim of this exploratory study was to investigate whether tumor type is related to the spatial tractography pattern of the frontal aslant tract (FAT) in low-grade gliomas (LGGs).

Methods

In 64 IDH-mutated LGG patients, the FAT was generated using a pipeline for automatic tractography. In 41 patients, the glioma adjoined the FAT, and four blinded reviewers independently assessed the following two dichotomous categories (yes/no): (i) glioma displaces the tract, and (ii) glioma infiltrates the tract.

Results

Fisher’s exact tests demonstrated strong and significant positive associations between displacement and astrocytomas (p = .002, φ = .497) and infiltration and oligodendrogliomas (p = .004, φ = .484). The interobserver agreement was good for both categories: (i) κ = 0.76 and (ii) κ = 0.71.

Conclusion

High sensitivity but low specificity for displacement in astrocytomas demonstrates that in the case of an astrocytoma, the tract is most likely displaced, but that displacement in itself is not necessarily predictive for astrocytomas, as oligodendrogliomas may both infiltrate and displace a tract. Overall, these results demonstrate that oligodendrogliomas tend to infiltrate the nearby subcortical tract, whereas astrocytomas only tend to displace it.
Risk factors for the development of tuberculosis among the pediatric population: a systematic review and meta-analysis
Authors: Siddalingaiah Nayana , Chawla Kiran , Nagaraja Sharath Burugina , Hazra Druti
Published: May 2023

Pediatric tuberculosis is a major cause of mortality and morbidity in children due to high transmission, poor diagnostic tools, and various respiratory diseases mimicking TB. Identifying risk factors will provide evidence for clinicians to strongly relate their diagnosis to the associated pathology. Studies were retrieved from PubMed, Embase, and Google Scholar, systematically reviewed, and meta-analyzed for various risk factors and their association with pediatric TB. Meta-analysis depicted that four out of eleven risk factors were significant—contact with known TB cases (OR 6.42 [3.85,10.71]), exposure to smoke (OR 2.61 [1.24, 5.51]), overcrowding in the houses (OR 2.29 [1.04, 5.03]), and, poor household conditions (OR 2.65 [1.38, 5.09]). Although significant odds ratio estimates were obtained, we observed heterogeneity in the studies included.

    Conclusion: The study findings demand the constant screening of risk factors such as contact with known TB cases, exposure to smoke, overcrowding, and, poor household conditions for the development of pediatric TB.

What is Known:• Knowledge of the risk factors of a disease is of utmost importance in the planning and institution of its control measures. Well-established risk factors in the occurrence of TB in the pediatric group are HIV positivity, older age and close contact with a known case of TB.

What is New:• In addition to what is already known; this review and meta-analysis has identified exposure to indoor smoking, overcrowding and poor household conditions as important risk factors for developing pediatric TB.• Implications of the study: The findings highlight that in addition to routine contact screening for the pediatric group, the children living in poor household conditions and getting exposed to passive indoor smoking demand more attention to prevent the development of pediatric TB.
Climate and human health: a review of publication trends in the International Journal of Biometeorology
Authors: Motlogeloa Ogone , Fitchett Jennifer M.
Published: May 2023

The climate-health nexus is well documented in the field of biometeorology. Since its inception, Biometeorology has in many ways become the umbrella under which much of this collaborative research has been conducted. Whilst a range of review papers have considered the development of biometeorological research and its coverage in this journal, and a few have reviewed the literature on specific diseases, none have focused on the sub-field of climate and health as a whole. Since its first issue in 1957, the International Journal of Biometeorology has published a total of 2183 papers that broadly consider human health and its relationship with climate. In this review, we identify a total of 180 (8.3%, n = 2183) of these papers that specifically focus on the intersection between meteorological variables and specific, named diagnosable diseases, and explore the publication trends thereof. The number of publications on climate and health in the journal increases considerably since 2011. The largest number of publications on the topic was in 2017 (18) followed by 2021 (17). Of the 180 studies conducted, respiratory diseases accounted for 37.2% of the publications, cardiovascular disease 17%, and cerebrovascular disease 11.1%. The literature on climate and health in the journal is dominated by studies from the global North, with a particular focus on Asia and Europe. Only 2.2% and 8.3% of these studies explore empirical evidence from the African continent and South America respectively. These findings highlight the importance of continued research on climate and human health, especially in low- and lower-middle-income countries, the populations of which are more vulnerable to climate-sensitive illnesses.
Wie werden langwirksame Wachstumshormonpräparate in Österreich von Ärzt*innen und Patienteneltern wahrgenommen?
Authors: Belic Jelena , Zekoll Theresa , Riedl Stefan , Windisch Manfred
Published: May 2023

Rekombinantes humanes Wachstumshormon muss aufgrund seiner kurzen Halbwertszeit täglich injiziert werden. Dieses Behandlungsregime kann für Patient*innen und ihre Familien eine ganz erhebliche Belastung darstellen. Langwirksame Wachstumshormone (LAGH) sind eine neuartige Behandlungsoption, die durch eine 1‑mal wöchentliche Verabreichung eine reduzierte Injektionsfrequenz ermöglicht. Um erste Erkenntnisse über die Erwartungen an diese neuen LAGH-Formulierungen zu gewinnen, wurden zwei Umfragen bei Ärzt*innen sowie Eltern von Kindern, die täglich mit Wachstumshormon behandelt werden, in Österreich durchgeführt. Zwanzig Pädiater*innen/pädiatrische Endokrinolog*innen und 41 Eltern wurden befragt. Beide Umfragen zeigten, dass die LAGH-Formulierungen als positive Therapiealternative gesehen werden und dadurch eine Verbesserung der Lebensqualität erwartet wird.
Anhaltend spannend – das zu kurze Zungenband, Teil 3
Authors: Guóth-Gumberger Márta , Karall Daniela
Published: May 2023

Die Zunge hat eine zentrale Aufgabe bei vielerlei Aufgaben. Stillen, angemessene Ernährung und altersgemäßer Gewichtsverlauf sind einige davon – und wichtige Anliegen in der Pädiatrie. Auch bei Problemen mit Essen, Aussprache, Schlucken oder Zahnstellung kann eine eingeschränkte Zungenbeweglichkeit durch ein zu kurzes Zungenband eine Rolle spielen, da dadurch die erforderlichen Lernprozesse für die Bewegung der Zunge behindert werden. Das Wissen um die möglichen Folgen eines zu kurzen Zungenbandes hat in den letzten Jahrzehnten vermehrt an Kenntnis gewonnen. Die ausgeprägte Variante des zu kurzen Zungenbandes, das Frenulum linguae breve anterior (oder: „zu kurzes Zungenband mit Ansatz an der Zungenspitze“), ist sichtbar und wird meist behandelt; seltener die posteriore Variante, das „zu kurze Zungenband mit Ansatz hinter der Zungenspitze“, bei der die Zungenspitze frei ist und keine Einkerbung zeigt.

Die Auseinandersetzung mit der Anatomie der Strukturen in der Mundhöhle, mit den unterschiedlichen Möglichkeiten der Beurteilung der Funktion der Zunge und der unterschiedlichen Möglichkeiten der Frenotomie als Behandlung eines zu kurzen Zungenbandes sollen die Beurteilung unterstützen, wann und bei wem eine Behandlung sinnvoll ist und wann nicht, und welche begleitenden Maßnahmen empfohlen werden sollten.

Wenn ein zu kurzes Zungenband unerkannt bleibt, wirken die zur Lösung der Symptome ergriffenen Maßnahmen oft nicht wie erwünscht. Daher ist es essenziell zu erkennen, wann eine Behandlung des zu kurzen Zungenbandes sinnvoll ist, wann nicht, und wie sie mit anderen Maßnahmen verbunden werden kann, damit das Ergebnis – nämlich eine verbesserte Beweglichkeit der Zunge für die erforderlichen Funktionen – erreicht wird.

In dieser dreiteiligen Serie zum Thema zu kurzes Zungenband wird ein vertiefter Überblick über das Thema geschaffen, insbesondere über den Zusammenhang mit Stillen, Ernährung, Gewichtsverlauf, Sprache und Zahnstellung.
Fractionated whole body γ-irradiation aggravates arthritic severity via boosting NLRP3 and RANKL expression in adjuvant-induced arthritis model: the mitigative potential of ebselen
Authors: Thabet Noura M. , Abdel-Rafei Mohamed K. , Amin Mohamed M.
Published: May 2023

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease associated with oxidative stress that causes excruciating pain, discomfort, and joint destruction. Ebselen (EB), a synthesized versatile organo-selenium compound, protects cells from reactive oxygen species (ROS)-induced injury by mimicking glutathione peroxidase (GPx) action. This study aimed to investigate the antioxidant and anti-inflammatory effects of EB in an arthritic irradiated model. This goal was achieved by subjecting adjuvant-induced arthritis (AIA) rats to fractionated whole body γ-irradiation (2 Gy/fraction once per week for 3 consecutive weeks, for a total dose of 6 Gy) and treating them with EB (20 mg/kg/day, p.o) or methotrexate (MTX; 0.05 mg/kg; twice/week, i.p) as a reference anti-RA drug. The arthritic clinical signs, oxidative stress and antioxidant biomarkers, inflammatory response, expression of NOD-like receptor protein-3 (NLRP-3) inflammasome, receptor activator of nuclear factor κB ligand (RANKL), nuclear factor-κB (NF-κB), apoptotic indicators (caspase 1 and caspase 3), cartilage integrity marker (collagen-II), and histopathological examination of ankle joints were assessed. EB notably improved the severity of arthritic clinical signs, alleviated joint histopathological lesions, modulated oxidative stress and inflammation in serum and synovium, as well as reduced NLRP-3, RANKL, and caspase3 expression while boosting collagen-II expression in the ankle joints of arthritic and arthritic irradiated rats with comparable potency to MTX. Our findings suggest that EB, through its antioxidant and anti-inflammatory properties, has anti-arthritic and radioprotective properties in an arthritic irradiated model.
Automated Medical Diagnosis of Alzheimer´s Disease Using an Efficient Net Convolutional Neural Network
Authors: Agarwal Deevyankar , Berbís Manuel Álvaro , Luna Antonio , Lipari Vivian , Ballester Julien Brito , de la Torre-Díez Isabel
Published: May 2023

Alzheimer's disease (AD) poses an enormous challenge to modern healthcare. Since 2017, researchers have been using deep learning (DL) models for the early detection of AD using neuroimaging biomarkers. In this paper, we implement the EfficietNet-b0 convolutional neural network (CNN) with a novel approach—"fusion of end-to-end and transfer learning"—to classify different stages of AD. 245 T1W MRI scans of cognitively normal (CN) subjects, 229 scans of AD subjects, and 229 scans of subjects with stable mild cognitive impairment (sMCI) were employed. Each scan was preprocessed using a standard pipeline. The proposed models were trained and evaluated using preprocessed scans. For the sMCI vs. AD classification task we obtained 95.29% accuracy and 95.35% area under the curve (AUC) for model training and 93.10% accuracy and 93.00% AUC for model testing. For the multiclass AD vs. CN vs. sMCI classification task we obtained 85.66% accuracy and 86% AUC for model training and 87.38% accuracy and 88.00% AUC for model testing. Based on our experimental results, we conclude that CNN-based DL models can be used to analyze complicated MRI scan features in clinical settings.
On the Application of Non-Gaussian Noise in Stochastic Langevin Simulations
Authors: Grønbech-Jensen Niels
Published: May 2023

In light of recent advances in time-step independent stochastic integrators for Langevin equations, we revisit the considerations for using non-Gaussian distributions for the thermal noise term in discrete-time thermostats. We find that the desirable time-step invariance of the modern methods is rooted in the Gaussian noise, and that deviations from this distribution will distort the Boltzmann statistics arising from the fluctuation-dissipation balance of the integrators. We use the GJ stochastic Verlet methods as the focus of our investigation since these methods are the ones that contain the most accurate thermodynamic measures of existing methods. Within this set of methods we find that any distribution of applied noise, which satisfies the two first moments given by the fluctuation-dissipation theorem, will result in correct, time-step independent results that are generated by the first two moments of the system coordinates. However, if non-Gaussian noise is applied, undesired deviations in higher moments of the system coordinates will appear to the detriment of several important thermodynamic measures that depend especially on the fourth moments. The deviations, induced by non-Gaussian noise, become significant with the one-time-step velocity attenuation, thereby inhibiting the benefits of the methods. Thus, we conclude that the application of Gaussian noise is necessary for reliable thermodynamic results when using modern stochastic thermostats with large time steps.
Tumor Treating Fields (TTFields) increase the effectiveness of temozolomide and lomustine in glioblastoma cell lines
Authors: Fishman Hila , Monin Roni , Dor-On Eyal , Kinzel Adrian , Haber Adi , Giladi Moshe , Weinberg Uri , Palti Yoram
Published: May 2023

Purpose

Tumor Treating Fields (TTFields) are electric fields that disrupt cellular processes critical for cancer cell viability and tumor progression, ultimately leading to cell death. TTFields therapy is approved for treatment of newly-diagnosed glioblastoma (GBM) concurrent with maintenance temozolomide (TMZ). Recently, the benefit of TMZ in combination with lomustine (CCNU) was demonstrated in patients with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. The addition of adjuvant TTFields to TMZ plus CCNU further improved patient outcomes, leading to a CE mark for this regimen. The current in vitro study aimed to elucidate the mechanism underlying the benefit of this treatment protocol.

Methods

Human GBM cell lines with different MGMT promoter methylation statuses were treated with TTFields, TMZ, and CCNU, and effectiveness was tested by cell count, apoptosis, colony formation, and DNA damage measurements. Expression levels of relevant DNA-repair proteins were examined by western blot analysis.

Results

TTFields concomitant with TMZ displayed an additive effect, irrespective of MGMT expression levels. TTFields concomitant with CCNU or with CCNU plus TMZ was additive in MGMT-expressing cells and synergistic in MGMT-non-expressing cells. TTFields downregulated the FA-BRCA pathway and increased DNA damage induced by the chemotherapy combination.

Conclusions

The results support the clinical benefit demonstrated for TTFields concomitant with TMZ plus CCNU. Since the FA-BRCA pathway is required for repair of DNA cross-links induced by CCNU in the absence of MGMT, the synergy demonstrated in MGMT promoter methylated cells when TTFields and CCNU were co-applied may be attributed to the BRCAness state induced by TTFields.
The Control and Comprehensive Safety Assessment of Heavy Metal Impurities (As, Pb, and Cd) in Green Tea Camellia sinensis (L.) Samples (Infusions) Available in Poland
Authors: Jurowski Kamil , Kondratowicz-Pietruszka Elżbieta , Krośniak Mirosław
Published: May 2023

Tea is the world’s most common drink after water, and the world’s annual sales exceed $43 billion, of which more than $11 billion is green tea (Camellia sinensis (L.)). Increasing evidence continues to show that green tea consumption and its ingredients have a variety of potential health benefits. The aim of the study was to control and assess the toxicological risk (TRA) of three heavy metals (As, Pb, and Cd) in infusions of green tea (n = 12) from Polish markets. We applied the method of inductive coupled plasma mass spectrometry (ICP-MS) to determine the selected heavy metal and designed a specific toxicological risk assessment with three crucial tiers. The first tier of our strategy was to determine the elements investigated (heavy metal impurities, µg/L). The second step was to estimate the weekly intake of green tea infusions (µg/week) based on weekly consumption. The third tier was to estimate the weekly intake per weight (µg/L/week/bw), based on the average weekly intake of green tea infusion per adult compared to the provisional weekly intake (PTWI) established by the FAO/WHO Joint Food Additives Expert Committee (JECFA). The levels of the investigated heavy metals occur at different levels in all of the investigated green tea infusions. The heavy metal profile indicated that As (0.0721–10.585 µg/L), Pb (0.386–1.695 µg/L), and Cd (0.126–0.346 µg/L) were present in all samples. Basic analysis of general content shows that As (average = 0.325 µg/L) was at a level similar to Cd (average = 0.214 µg/L). Surprisingly, the Pb content (average 0.891 µg/L) was approximately 2.75–4 times higher than that of As and Cd, respectively. The application of our proposed safety assessment methodology (three tiers) provides satisfactory results for regulatory purposes. The evaluation of the investigated heavy metals in all products analysed from green tea samples (infusions) showed that there were no health hazards to consumers due to weekly exposure. The results indicated that after drinking green tea infusions from Polish markets, the amount of investigated elements in weekly doses does not represent any health risks to consumers.
ANXA6: a key molecular player in cancer progression and drug resistance
Authors: Cao Jinlong , Wan Shun , Chen Siyu , Yang Li
Published: May 2023

Annexin-A6 (ANXA6), a Ca2+-dependent membrane binding protein, is the largest of all conserved annexin families and highly expressed in the plasma membrane and endosomal compartments. As a multifunctional scaffold protein, ANXA6 can interact with phospholipid membranes and various signaling proteins. These properties enable ANXA6 to participate in signal transduction, cholesterol homeostasis, intracellular/extracellular membrane transport, and repair of membrane domains, etc. Many studies have demonstrated that the expression of ANXA6 is consistently altered during tumor formation and progression. ANXA6 is currently known to mediate different patterns of tumor progression in different cancer types through multiple cancer-type specific mechanisms. ANXA6 is a potentially valuable marker in the diagnosis, progression, and treatment strategy of various cancers. This review mainly summarizes recent findings on the mechanism of tumor formation, development, and drug resistance of ANXA6. The contents reviewed herein may expand researchers’ understanding of ANXA6 and contribute to developing ANXA6-based diagnostic and therapeutic strategies.
Case report. Spermatocytaire tumor: een zeldzame testiculaire tumor
Authors: van Renterghem Alexander R. P. K. M. , Laguna M. Pilar , Ferong Kristel B. M. , Clarijs Ruud , Jacobs Rens A. L.
Published: May 2023

Samenvatting

Een spermatocytaire tumor is met een incidentie van 1–12% een zeldzame vorm van testiculaire tumor. De tumor heeft kleine kans op metastasering, tenzij er in de tumor sprake is van sarcomatoïde of anaplastische transformatie. Een orchidectomie is de standaard behandeling. Adjuvante therapie is zelden noodzakelijk. We beschrijven de casus van een 68-jarige man die werd verwezen naar ons centrum met een harde palpabele massa in het linker hemiscrotum. Echografisch onderzoek van het scrotum toonde twee echoarme gelobde nodulaire letsels. De tumormarkers waren niet verhoogd. Er werd een radicale inguïnale orchidectomie verricht en daarop volgend histopathologisch onderzoek toonde een spermatocytaire tumor aan. Kennis over spermatocytaire tumoren is essentieel. Kortdurende follow-up middels CT-scan en lichamelijk onderzoek wordt aangeraden.
Small divisors in discrete local holomorphic dynamics
Authors: Reppekus Josias
Published: May 2023

We give an introduction to the study of local dynamics of iterated holomorphic mappings near a fixed point via local conjugations in one and several complex variables. Starting with the systematic construction of formal conjugations to Poincaré–Dulac normal form in general and formal linearisations in particular, we discuss conditions for convergence of the normalising series in terms of the linear part. The convergence is closely related to the size of denominators that show up in the normalising series and depend only on the linear part of the mapping. Hence, we speak of a small-divisor problem. The central result on the linearisation problem is the Brjuno condition, that ensures holomorphic linearisability. The first part of these notes is a survey of the local dynamics in one variable from the viewpoint of local normalisations. In this case, the picture is fairly complete. In the second part we introduce the additional obstacles to both formal and holomorphic normalisations that emerge from interactions of multiple eigenvalues, such as resonances, that preclude the Brjuno condition in particular. For these cases, we proceed with several generalisations of the Brjuno condition, that allow us to find convergent conjugations to at least partial normalisations. The last part reviews a recent application of such a partial normalisation to illuminate the local dynamics near certain one-resonant fixed points.
The Case Against a Special Regime for Intragroup Transactions
Authors: Enriques Luca , Gilotta Sergio
Published: May 2023

Corporate groups with minority shareholders in one or more subsidiaries are common around the world, despite the risks such arrangements pose to those shareholders. Shaping a firm as a web of formally independent, minority-co-owned legal entities facilitates controllers’ diversion of corporate wealth (tunnelling) via intragroup transactions and other non-transactional techniques. While many jurisdictions leave the regulation of intragroup transactions to ordinary remedies against self-dealing, others (mostly in Europe) establish a special regime centred on a relaxation of directors’ fiduciary duties. Under this special regime, subsidiary directors are not liable if they make disadvantageous decisions that are beneficial to other entities within their group, provided that proper compensation is granted (or, according to some proposals, may reasonably be expected to be granted) to the subsidiary. This article conducts a qualitative cost-benefit analysis of the special regime, focusing on the European Model Companies Act’s rules on intragroup transactions. We concede that such rules have the advantage of reducing contracting costs and enhancing managerial flexibility within the corporate group, relative to systems governed by ordinary corporate law rules against unfair self-dealing. However, we also show that those benefits can be expected to be very limited. Furthermore, we show that this special regime substantially reduces minority shareholder protection against tunnelling, by making it much harder for minority shareholders to recover damages from controllers’ unfair self-dealing. Overall, our analysis suggests that, for corporate groups with minority shareholders at the subsidiary level, this regime should be implemented as an opt-in arrangement, if at all. Even in that form, it should be adopted together with adequate protections for shareholders dissenting from the midstream resolution to opt into the regime.
Justice vis à vis welfare: how Austrian welfare economics should fit in the Austro-libertarian framework
Authors: Wysocki Igor
Published: May 2023

The present work calls for a modification of Austrian welfare economics so that it should be given adistinctrole within the Austro-libertarian paradigm. To this end, we clearly distinguish between justice and welfare. We proceed by trying to stick to the spirit of Austro-libertarianism as firmly as possible. In particular, we operate within the universe of voluntary (viz. rights-respecting) exchanges, having assumed thelibertarianabsolutist side-constraints view of rights. Furthermore, we take for granted the Austrianactual preference satisfaction view. The specific purpose of the present paper is two-fold. First, we subject Austrian rights-based welfare economics to critical scrutiny. Concluding that the above theory begs the question in favor of free market, we assert that to gauge marketefficiencywe need to resort to somedescriptivecriterion, which could reasonably be deemed constitutive of welfare. And it is only then that the question of market efficiency is an open question.
Nonlinear flow and permeability anisotropy characteristics in hydraulic fracturing-induced rock fractures subjected to various normal compressive stresses
Authors: Chen Junchao , Che Zhenglu , Su Xiaopeng , Zhou Lei , Liu Xiaofei , Zhang Liang
Published: May 2023

Well productivity after hydraulic fracturing is strongly affected by the flow behaviors in created fracture complexity. In this study, gas flow tests were conducted in splitting fractures (induced by Brazilian splitting) and hydraulic fractures (created by hydraulic fracturing) to study the nonlinear fluid flow behaviors in rough fractures. 3D fracture surfaces were first digitally reproduced with a scanner and then the fracture geometry parameters (roughness profile index $$R_{p}$$

R
p

, the root mean square of the fracture profile wall slope $$Z_{2}$$

Z
2

), aperture distributions were computed for both fractures. The influence of the fracture geometry characteristics on the nonlinear flow behaviors were systematically analyzed. The permeability anisotropy was numerically examined in detail. The results show that $$R_{p}$$

R
p

, $$Z_{2}$$

Z
2

and mean aperture of hydraulic fractures are relatively smaller, indicating that the fracture surfaces are smoother. The transmissivity of splitting fracture is relatively higher than that of hydraulic ones, and the ratio of splitting to hydraulic one varies from 2.51 at $$\sigma_{c}$$

σ
c

 = 1 MPa to 60.95 at $$\sigma_{c}$$

σ
c

 = 40 MPa. By contrast, splitting fractures have larger critical Reynolds number and lower critical pressure gradient, implying that nonlinearity is easier to occur in splitting fractures. The average Forchheimer coefficient for splitting fractures is 0.00577, which is 1.5 times larger than that (0.0041) for hydraulic ones. In addition, the fractures exhibit strong permeability anisotropy and this anisotropic effect is significantly dependent on the loading stress. In general, the permeability anisotropy in hydraulic fracture is more significant, showing that their permeability anisotropy ratios $$K$$
K
are larger and more sensitive to the loading. The obtained results confirm that there exist some discrepancies in flow behaviors between splitting and hydraulic fractures and for more accurate evaluation in engineering practice, hydraulic fractures should be fully considered.
Estimating the Demand for Groundwater: A Second-stage Hedonic Land Price Analysis for the Lower Mississippi River Alluvial Plain, Arkansas
Authors: Kovacs Kent , Rider Shelby
Published: May 2023

We estimate the benefits of the saturated thickness (water-bearing porous material) of the alluvial aquifer in Arkansas through an application of the hedonic price model to the sale of agricultural land. There is evidence from the first-stage analysis of diminishing returns from increasing saturated thickness. Using a survey of farmer operators’ preferences and socioeconomic characteristics, we recover the underlying demand function for saturated thickness in a second-stage analysis. Shifts in the demand function reveal that produced/social capital can be a substitute or a complement to saturated thickness, and human capital is a substitute for saturated thickness.
Methicillin-resistant Staphylococcus aureus bacteremia with elevated vancomycin minimum inhibitory concentrations
Authors: Mills Alexandra G. , Dupper Amy C. , Chacko Kieran I. , Alburquerque Bremy , Nadkarni Devika , Berbel Caban Ana , Fox Lindsey , Gitman Melissa R. , Obla Ajay , van Bakel Harm , Altman Deena R.
Published: May 2023

This case–control study of 25 cases with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with vancomycin minimum inhibitory concentration (MIC) ≥ 2 µg/mL and 391 controls (MIC < 2 µg/mL) characterized the clinical characteristics, treatments, and outcomes associated with elevated vancomycin MIC. Elevated vancomycin MIC was associated with baseline hemodialysis, prior MRSA colonization, and metastatic infection.
Can AI design life?
Authors: Bashton Matthew
Published: May 2023

Artificial intelligence (AI) has advanced considerably, AlphaFold2 protein models are as good as X-ray results, language models like ChatGPT can pass MBA and medical exams, and deep learning models Midjourney, and Stable Diffusion can emulate artistic styles. Given current progress, could text-based inputs be used for the generative design of artificial proteins, pathways, or even organisms, with traits designed purely by AI? Existing strategies for biotechnology design are founded in knowledge-based approaches, such as rational enzyme engineering or whole pathway design using synthetic biology, often borrowing “parts” from other organisms. Alternatively, desired traits are achieved via random mutagenesis with iterative selection procedures. Both are costly in terms of acquiring knowledge and undertaking experimentation. Recently, advances in protein language models have allowed AI to implicitly “learn” properties that allow sequences to be folded alongside other embedded learning techniques for function prediction from primary sequences. Thus, AI offers varied routes to predicting biological outcomes from DNA sequences. However, AI has not yet been extensively used to design novel functions, despite the wealth of functionally annotated protein products at our fingertips. Thus, generative protein language models for biodesign represent a promising future. We seek to explore current technological limits and challenges, investigate new avenues and methodologies to make this possible and broach discussion around wider issues arising from AI-designed life.
The virtuous smart city: Bridging the gap between ethical principles and practices of data-driven innovation
Authors: Lähteenoja Viivi , Karhu Kimmo
Published: May 2023

For smart cities, data-driven innovation promises societal benefits and increased well-being for residents and visitors. At the same time, the deployment of data-driven innovation poses significant ethical challenges. Although cities and other public-sector actors have increasingly adopted ethical principles, employing them in practice remains challenging. In this commentary, we use a virtue-based approach that bridges the gap between abstract principles and the daily work of practitioners who engage in and with data-driven innovation processes. Inspired by Aristotle, we describe practices of data-driven innovation in a smart city applying the concepts of virtue and phronêsis, meaning good judgment of and sensitivity to ethical issues. We use a dialogic case-study approach to study two cases of data-driven innovation in the city of Helsinki. We then describe as an illustration of how our approach can help bridge the gap between concrete practices of data-driven innovation and high-level principles. Overall, we advance a theoretically grounded, virtue-based approach, which is practice oriented and linked to the daily work of data scientists and other practitioners of data-driven innovation. Further, this approach helps understand the need for and importance of individual application of phronêsis, which is particularly important in public-sector organizations that can experience gaps between principle and practice. This importance is further intensified in cases of data-driven innovation in which, by definition, novel and unknown contexts are explored.
Descriptive Analysis of the Healthcare Aspects of Industrial Disasters Around the World
Authors: Tin Derrick , Cheng Lenard , Hata Ryan , Hertelendy Attila J. , Hart Alexander , Ciottone Gregory
Published: May 2023

Objective:

Industrial disasters can have a myriad of repercussions ranging from deaths, injuries, and long-term adverse health impacts on nearby populations, to political fallout and environmental damage. This is a descriptive epidemiological analysis of industrial disasters occurring between 1995 and 2021 which may provide useful insight for health-care systems and disaster medicine specialists to better prevent and mitigate the effects of future industrial disasters.

Methods:

Data were collected using a retrospective database search of the Emergency Events Database (EM-DATS) for all industrial disasters occurring between January 1, 1995, and December 31, 2021.

Results:

A total of 1054 industrial disasters were recorded from 1995 to 2021. Most of these disasters occurred in Asia (720; 68.3%), with 131 (12.4%) in Africa, 107 (10.2%) in Europe, 94 (8.9%) in the Americas, and 2 (0.2%) in Oceania. Half of these disasters were explosions (533; 50.6%), 147 (13.9%) were collapses, 143 (13.6%) were fires, 46 (4.4%) were chemical spills, 41 (3.9%) were gas leaks, and 34 (3.2%) were poisonings. There were 6 (0.6%) oil spills and 3 (0.3%) radiation events.

Conclusions:

A total of 29,708 deaths and 57,605 injuries were recorded as a result of industrial disasters, and they remain a significant contributor to the health-care risks of both workers and regional communities. The need for specialized emergency response training, the potential devastation of an industrial accident, and the vulnerability of critical infrastructure as terror targets highlight the need to better understand the potential immediate and long-term consequences of such events and to improve health-care responses in the future.