bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Health and Self-Management in Idiopathic Inflammatory Myopathies: A Missed Opportunity?
Authors: Battista Simone , Giardulli Benedetto , Sieiro Santos Cristiana , Aharonov Or , Puttaswamy Darshan , Russell Anne – Marie , Gupta Latika
Published: August 2024

Purpose of Review

This paper explored the potential of digital health in idiopathic inflammatory myopathies (IIMs), with a focus on self-management. Digital self-management technology includes tailored treatment plans, symptom tracking, educational resources, enhanced communication, and support for long-term planning.

Recent Findings

After arguing the importance of digital health in IIMs management, from diagnosis until treatment, our literature review revealed a notable gap in research focusing on the efficacy of digital self-management interventions for individuals with IIMs, with no randomised controlled trials or observational studies addressing this topic.

Our review further highlighted the significant unmet need for research in self-management interventions for individuals with IIMs. The absence of studies underscores the necessity for collaborative efforts to address this gap and develop personalised, effective strategies for managing IIMs using digital technology. Individuals with IIMs deserve tailored self-management approaches akin to those available for other rheumatic and musculoskeletal diseases.
Patterns of Heterosexual Sex in Popular Netflix Series: A Content Analysis of Age, Race, Face Attractiveness, and Body Type
Authors: Oschatz Tanja , Döring Nicola , Zimmermanns Christin , Klein Verena
Published: August 2024

The portrayal of diverse ages, races, face attractiveness, and body types in sexual media content might impact societal perceptions of sexuality, delineating which individuals are deemed sexually appealing and whose sexuality is normalized. Despite extensive research on demographics within pornography, the representation within mainstream media, particularly on streaming platforms like Netflix, remains underexplored. The current study addresses this gap by employing quantitative content analysis to examine the diversity of characters in sexual contexts within seven highly popular Netflix series. We coded the age, race, face attractiveness, and body type of 91 characters (45 female characters) that appeared in mixed-gender sexual encounters (i.e., sexual encounters between a woman and a man). The study reveals a predominant adherence to stereotypical demographics and conventional beauty standards. The sexual scenes presented mostly younger individuals and revealed a notable underrepresentation of individuals aged 40 +. Racial diversity among characters was more evident. Female characters were predominantly depicted as conventionally attractive and were almost exclusively portrayed with skinny body types, while male characters exhibited a wider range of physical appearances. This study highlights a gap in the media’s inclusivity efforts and suggests a need for more comprehensive representation to reflect a broader spectrum of age and beauty ideals in the portrayals of human sexuality. While our study is limited to analyzing media representations, future research should include longitudinal experimental studies to evaluate their impact on people’s sexualities.
It is all about discomfort avoidance: maladaptive daydreaming, frustration intolerance, and coping strategies – a network analysis
Authors: Nowacki Ari , Pyszkowska Anna
Published: August 2024

Maladaptive daydreaming (MD) is a need to daydream that replaces human interactions and disturbs everyday life. Research suggests that MD can be considered a stress-relief strategy, as a repeating sequence of using imagination may play a significant role in calming oneself down and seeking comfort through escapism and avoidance. The current study explored the relationships between maladaptive daydreaming, coping styles, and frustration intolerance (including discomfort and emotional intolerance) in a general population. The sample was divided into two subgroups: maladaptive daydreamers (MDers) and non-maladaptive daydreamers (non-MDers) based on the cutoff score in the Maladaptive Daydreaming Scale-16 (MDS-16). Three hundred seventeen individuals participated in the study, including 142 MDers. The results showed significantly higher levels of frustration intolerance (U = 9952.00, p <.01) and avoidance-focused strategies (U = 10170.00, p <.01) among the MDers. Non-MDers scored significantly higher on the Emotional support-seeking scale (U = 16117.50, p <.001). Additionally, the network analysis proved differences in the variables’ dynamics: only in the MDers network MD exhibited significant edges with avoidant coping (0.05), discomfort intolerance (0.10), entitlement (0.07), and emotional intolerance (0.10). Entitlement was the variable of the highest expected influence in both subgroups studied. The current study proposes clinical implications: as emotional intolerance may serve as an essential factor in maintaining engagement in maladaptive daydreaming, the role of discomfort intolerance and its links to avoidance should be of significant focus in MD therapy.
The genus Hypobathrum (Rubiaceae) in Thailand
Authors: Yooprasert Sawita , Bilsborrow Jordan , Utteridge Timothy M. A.
Published: August 2024

The genus Hypobathrum in Thailand is revised, based on the morphological characters found in herbarium specimens from Thailand and neighbouring countries including Bangladesh, Myanmar, Cambodia and Peninsular Malaysia. In this study, three species of Hypobathrum are recognised, among them, H. venulosum is a newly recorded species in this region. An identification key is provided for the species, along with descriptions, synonyms, distribution ranges and vernacular names (if available).
Impact of radiative cooling on the energy performance of courtyards in Mediterranean climate
Authors: Domínguez-Torres Carlos-Antonio , Domínguez-Delgado Antonio
Published: August 2024

Radiative cooling has proven to be a useful tool to address the problems of lack of comfort and excessive energy consumption in situations of high temperatures, overheating and heat waves. Likewise, incorporating courtyards in warm climate zones has been found to be highly beneficial in addressing similar challenges. Hence, there is interest in analyzing the combined effects of both: radiative cooling and courtyards. This paper presents an analysis of the impact of the application of radiative cooling on a courtyard using a comprehensive simulation approach that includes a CFD model for the thermodynamic airflow in the adjacent roofs and inside the courtyard, equations for the transient heat conduction through roofs, walls and courtyard slabs, and a hybrid raytracing-radiosity model for the evaluation of the solar radiation reaching the building surfaces and its reflections, both of specular and diffuse origin, and for the calculation of the thermal radiation exchange, especially with the sky. The results show that in the hot season, the courtyard with radiative cooling always provides lower temperatures than the initial courtyard does, with a temperature range of 18.33 °C to 33.78 °C, compared to a range of 19.32 °C to 38.00 °C in the initial courtyard, and producing a greater difference with outdoor temperatures that can reach 12 °C versus 8 °C for the reference case. In addition, it was found that the courtyard with radiative cooling is able to significantly reduce the observed nighttime overheating by providing lower temperatures than the outdoor temperatures in the 50% of the nights studied. It was also found that the thermal loads to achieve indoor thermal comfort in the spaces adjacent to the courtyard were reduced by 63.46% to 69.85%.
Potential anatomical triggers for plan adaptation of cervical cancer external beam radiotherapy
Authors: Brown Rhianna , Holloway Lois , Lau Annie , Lim Karen , Moodaley Pereshin , Metcalfe Peter , Do Viet , Cutajar Dean , Walker Amy
Published: August 2024

This study aimed to identify potential anatomical variation triggers using magnetic resonance imaging for plan adaption of cervical cancer patients to ensure dose requirements were met over an external beam radiotherapy course. Magnetic resonance images (MRIs) acquired before and during treatment were rigidly registered to a pre-treatment computerised tomography (CT) image for 11 retrospective cervix cancer datasets. Target volumes (TVs) and organs at risk (OARs) were delineated on both MRIs and propagated onto the CT. Treatment plans were generated based on the pre-treatment contours and applied to the mid-treatment contours. Anatomical and dosimetric changes between each timepoint were assessed. The anatomical changes included the change in centroid position and volume size. Dosimetric changes included the V30Gy and V40Gy for the OARs, and V95%, V100%, D95% and D98% for the TVs. Correlation with dosimetric and anatomical changes were assessed to determine potential replan triggers. Changes in the bowel volume and position in the superior-inferior direction, and the high-risk CTV anterior posterior position were highly correlated with a change in dose to the bowel and target, respectively. Hence changes in bowel and high-risk CTV could be used as a potential replan triggers.
Microstructural Characterization of Eutectics using Digital Image Analysis
Authors: Bortnyik Kornél , Gyöngyösi Szilvia , Barkóczy Péter
Published: August 2024

Metallic eutectics play an important role in casting technology and properties. For this reason, the study of eutectics microstructure is indispensable in the casting qualification. Eutectics have many similar characteristics, including the morphology, size and spatial arrangement of eutectic phases. This makes it possible to develop a method of general use based on analyzing eutectic microscopy images. The method presented in this article performs a posteriori background correction for OM images. The shape and size of phases are determined using cellular automata and machine learning. Another cellular automaton and cluster analysis characterizes the spatial arrangement of eutectic phases. It can also be used to determine the distance between objects both locally and within a given object group. The algorithm is suitable for exploring and examining the spatial clustering of objects. The methods can be included in an algorithm, so a detailed examination of the eutectic microstructure can be carried out. The method was tested on micrographs of Al-Cu, Al-Ni, Al-Si and cast irons.
Selective CO2 Electroreduction to Multi-Carbon Products on Organic-Functionalized CuO Nanoparticles by Local Micro-Environment Modulation
Authors: Ren Shan , Cao Xi , Fan Qikui , Yang Zhimao , Wang Fei , Wang Xin , Bai Licheng , Yang Jian
Published: August 2024

Surface functionalization of Cu-based catalysts has demonstrated promising potential for enhancing the electrochemical CO2 reduction reaction (CO2RR) toward multi-carbon (C2+) products, primarily by suppressing the parasitic hydrogen evolution reaction and facilitating a localized CO2/CO concentration at the electrode. Building upon this approach, we developed surface-functionalized catalysts with exceptional activity and selectivity for electrocatalytic CO2RR to C2+ in a neutral electrolyte. Employing CuO nanoparticles coated with hexaethynylbenzene organic molecules (HEB-CuO NPs), a remarkable C2+ Faradaic efficiency of nearly 90% was achieved at an unprecedented current density of 300 mA cm−2, and a high FE (> 80%) was maintained at a wide range of current densities (100–600 mA cm−2) in neutral environments using a flow cell. Furthermore, in a membrane electrode assembly (MEA) electrolyzer, 86.14% FEC2+ was achieved at a partial current density of 387.6 mA cm−2 while maintaining continuous operation for over 50 h at a current density of 200 mA cm−2. In-situ spectroscopy studies and molecular dynamics simulations reveal that reducing the coverage of coordinated K⋅H2O water increased the probability of intermediate reactants (CO) interacting with the surface, thereby promoting efficient C–C coupling and enhancing the yield of C2+ products. This advancement offers significant potential for optimizing local micro-environments for sustainable and highly efficient C2+ production.
The Associations between Anti-Bullying Interventions and Bullying and Cyberbullying Rates in Albanian Schools
Authors: Ismaili Emanuela , Rama Rudina , Strohmeier Dagmar , Yanagida Takuya , Gradinger Petra , Dragoti Edmond
Published: August 2024

To tackle school bullying, teachers can implement school, class, parent, or individual level activities. Applying a socio-ecological model of development, the present study (1) investigates which prevention and intervention activities are implemented in Albanian schools according to teacher perspectives, and (2) examines how these teacher-reported activities are associated with bullying and cyberbullying rates reported both by teachers and students. Representative data in schools all over Albania were collected via a stratified sampling procedure to select schools and a random sample method to select teachers and students. In total, 144 schools serving grades 4 to 12 and 3560 teachers (81% female) and 2377 students (54% girls) participated. The teachers indicated which school, class, parent, or individual level activities have been implemented in their school by answering a 14-item self-report. Both teachers and students reported the bullying and cyberbullying rates in their schools by answering an Olweus-type questionnaire. Multilevel confirmatory factor analysis and multilevel structural equation modeling on school level was applied to answer the research questions. Remarkably, the teacher and student perspectives regarding bullying and cyberbullying rates were not significantly correlated. Higher bullying and cyberbullying rates reported by teachers were significantly associated with higher levels of individual level activities, but with lower levels of class level activities. There were no associations between teacher reported intervention strategies and student reported bullying and cyberbullying rates. The study has major implications for the anti-bullying work in Albanian schools.
»Relationships are Key« A Semantic Relationship Awareness Framework for Operational Technology Monitoring
Authors: Schwinger W. , Kapsammer E. , Retschitzegger W. , Pröll B. , Graf D. , Baumgartner N. , Plöckinger V. , Schönböck J.
Published: August 2024

Critical infrastructures in areas like road traffic management naturally rely on the broad use of"Operational Technology (OT)"to ensure efficient and saferoad traffic monitoring (RTM)through"OT objects", like sensors and actuators, whereby monitoring OT itself("OTM")is evenly crucial. OTM is highly challenging, not least due tomassive heterogeneity of OT, immense complexity and size, andomnipresence of evolution. As a consequence, knowledge aboutinterdependencies between OT objectsin form ofsemantic relationshipsis often outdated or simply not available. Thus, in case of incidents, detection of cause and effect in the sense of asituational picture of OTis missing. In order to counteract this fundamental deficiency, we aim toautomatically discover semantic relationships between OT objects, to build up anontological knowledge baseas prerequisite for achievingOT situation awareness. Thereby, the contribution of this paper is threefold. First, a systematic exploration of the induced challenges is provided, derived from anin-depth analysis of real-world OT message logsin the area of RTM. Based on that, we sketch out a research roadmap, thereby guiding the identification of existing concepts and technologies appearing to be useful for realizing aframework for semantic relationship awareness, being the crucial pre-step for achieving OT situation awareness. Finally, a firstproof-of-concept prototypeis put forward, complemented by an evaluation of its applicability and a detailed comparison to related approaches.
Bringing practical statistical science to AI and predictive model fairness testing
Authors: Lo Victor S. Y. , Datta Sayan , Salami Youssouf
Published: August 2024

Artificial Intelligence, Machine Learning, Statistical Modeling and Predictive Analytics have been widely used in various industries for a long time. More recently, AI Model Governance including AI Ethics has received significant attention from academia, industry, and regulatory agencies. To minimize potential unjustified treatment disfavoring individuals based on demographics, an increasingly critical task is to assess group fairness through some established metrics. Many commercial and open-source tools are now available to support the computations of these fairness metrics. However, this area is largely based on rules, e.g., metrics within a prespecified range would be considered satisfactory. These metrics are statistical estimates and are often based on limited sample data and therefore subject to sampling variability. For instance, if a fairness criterion is barely met or missed, it is often uncertain if it should be a “pass” or “failure,” if the sample size is not large. This is where statistical science can help. Specifically, statistical hypothesis testing enables us to determine whether the sample data can support a particular hypothesis (e.g., falling within an acceptable range) or the observations may have happened by chance. Drawing upon the bioequivalence literature from medicine and advanced hypothesis testing in statistics, we propose a practical statistical significance testing method to enhance the current rule-based process for model fairness testing and its associated power calculation, followed by an illustration with a realistic example.
Symmetries and Separation of Variables
Authors: Rosenhaus V. , Shankar Ravi , Squellati Cody
Published: August 2024

In this paper, we look at the method of separation of variables of a PDE from its symmetry transformation point of view. Specifically, we discuss the relation between the existence of additively and multiplicatively separated variables of a PDE, and the form of its symmetry operators. We show that solutions in the form of separated variables are in fact, invariant solutions, i.e. solutions invariant under some subalgebra of the symmetry operators of the equation. For the case of two independent variables, we obtain the form of Lie point symmetry operators corresponding to additively and multiplicatively separated solutions, and generalize our results for the case when separated variables are any functions of independent variables. We also discuss the role of contact symmetry transformations and differential invariants for the existence of separated solutions, and outline the role of variational symmetries, as well as conditional (non-classical) symmetry operators. We demonstrate that the symmetry approach is a valuable tool for obtaining information regarding existence of solutions with separated variables.
Group-theoretical study of band nodes and the emanating nodal structures in crystalline materials
Authors: Tang Feng , Wan Xiangang
Published: August 2024

Topological materials usually possess protected gapless states in either the boundary or bulk, exhibiting various properties such as spin-momentum locking, Klein tunneling, Fermi arcs and so on. Database searches using symmetry data at high-symmetry points have catalogued thousands of topological materials revealing a magnitude of band nodes (BNs) at high-symmetry points or lying within high-symmetry lines/planes. A complete mapping from symmetry data (namely, representation of little group) in any BN to the $k\cdot p$
k
⋅
p
model characterizing low-energy Hamiltonian around the BN (and from the $k\cdot p$
k
⋅
p
model to concrete BN, inversely), is expected to complete the characterization of all BNs and gapless states. Here we first review recent progress on classifying BNs by systematically and automatically constructing $k\cdot p$
k
⋅
p
models based on recently completed tabulation of all irreducible (co-)representation matrices of little groups of the 1651 magnetic space groups. As one indispensable input in constructing a symmetry-allowed and generic $k\cdot p$
k
⋅
p
model, the expansion order, has been carefully and systematically truncated for any BN to a reasonable nonzero integer, by comparing the emanating nodal structure (ENS, including nodal point, nodal line and nodal surface) near the BN obtained by the explicitly constructed $k\cdot p$
k
⋅
p
model and that by pure symmetry analysis using compatibility relations (CRs). Owing to the progress, we are able to summarize all 25 different configurations of ENS near BN required by CRs, provide a complete mapping from $k\cdot p$
k
⋅
p
model to its realization around BN, and the corresponding ENS by CRs in an accessible file, and also reveal the protection mechanism of additional nodal lines that escape conventional analysis by CRs and is only predictable by constructing $k\cdot p$
k
⋅
p
model. The symmetry-based classification results on all BNs could facilitate large-scale materials prediction and hold promise for realizing topological semimetals suitable for device applications.
Antarctic Warm Extremes Across Seasons and Their Response to Advection
Authors: Xu Min , Pithan Felix , Yang Qinghua
Published: August 2024

Antarctic warm extremes impact the cryosphere, with very warm extremes driving surface melt on ice shelves. Here, we analyze temperatures exceeding the 90th percentile and the associated circulation patterns and radiation anomalies. ERA5 reanalysis data show positive geopotential height anomalies related to the occurrence of warm extremes. The highest temperature during warm extremes appears on the western periphery of high‐pressure systems, consistent with anticyclonic advection. Temperature anomalies during warm extremes are strongest in winter due to the transport of warm and moist air and a strong meridional temperature gradient. In summer, the weak meridional gradients of top‐of‐atmosphere downward solar radiation flux and surface air temperature contribute to weak temperature anomalies. Warm extremes are associated with positive longwave radiation anomalies in all seasons, but with negative shortwave radiation anomalies at the surface except during polar night. These relationships are verified by station observations. Our results confirm that Antarctic warm extremes are mostly driven by meridional advection of warm air, and suggest that these warm air masses are predominantly moist and cloudy.
Intermittency of Waves in the Polar Upper Troposphere and Lower Stratosphere Over Northern Norway Using MAARSY
Authors: Ghosh Priyanka , Renkwitz Toralf , Holt Laura , Tsutsumi Masaki , Latteck Ralph , Chau Jorge L.
Published: August 2024

We investigate the absolute momentum flux (AMF) and vertical wind variance of gravity waves (GWs) along with intermittencies in the upper troposphere and lower stratosphere (UTLS) during 2017–2022 using the Middle Atmosphere Alomar Radar System at Andøya, Norway (69.30°N, 16.04°E). We categorized the AMF and into different period ranges (30 min–2 hr, 2–6 hr, 6–13 hr, 13 hr–1 day, and 30 min–1 day) to study the significance of short‐ and long‐period waves. The selection of these period bands was based on the boundary conditions of the available spectra: 30 min (Nyquist frequency), 13 hr (inertial period), and 1 day (based on our interest in maximum long‐period oscillations). Through the investigation of the AMF and , we wish to determine in detail the GW characteristics at northern polar latitudes. Furthermore, it is crucial to assess the intermittency as it considerably influences and alters the GW attributes. Our novel results indicate for both AMF and : (a) seasonal variation with minima during summer (May–September); (b) higher magnitude in the upper troposphere (<9.00 km) than the lower stratosphere; (c) short‐period components (30 min–2 hr, 2–6 hr) are more intermittent in the entire UTLS; and (d) the long‐period components (6–13 hr, 13 hr–1 day) demonstrate lower (higher) intermittency in the upper troposphere (lower stratosphere) in summer implying a plausible wave‐filtering mechanism.
On Energy‐Aware Hybrid Models
Authors: Shevchenko Igor , Crisan Dan
Published: August 2024

This study proposes deterministic and stochastic energy‐aware hybrid models that should enable simulations of idealized and primitive‐equations Geophysical Fluid Dynamics (GFD) models at low resolutions without compromising on quality compared with high‐resolution runs. Such hybrid models bridge the data‐driven and physics‐driven modeling paradigms by combining regional stability and classical GFD models at low resolution that cannot reproduce high‐resolution reference flow features (large‐scale flows and small‐scale vortices) which are, however, resolved. Hybrid models use an energy‐aware correction of advection velocity and extra forcing compensating for the drift of the low‐resolution model away from the reference phase space. The main advantages of hybrid models are that they allow for physics‐driven flow recombination within the reference energy band, reproduce resolved reference flow features, and produce more accurate ensemble forecasts than their classical GFD counterparts. Hybrid models offer appealing benefits and flexibility to the modeling and forecasting communities, as they are computationally cheap and can use both numerically‐computed flows and observations from different sources. All these suggest that the hybrid approach has the potential to exploit low‐resolution models for long‐term weather forecasts and climate projections thus offering a new cost effective way of GFD modeling. The proposed hybrid approach has been tested on a three‐layer quasi‐geostrophic model for a beta‐plane Gulf Stream flow configuration. The results show that the low‐resolution hybrid model reproduces the reference flow features that are resolved on the coarse grid and also gives a more accurate ensemble forecast than the physics‐driven model.
Hepatocyte-specific loss of melanocortin 1 receptor disturbs fatty acid metabolism and promotes adipocyte hypertrophy
Authors: Thapa Keshav , Ghimire Bishwa , Pokharel Kisun , Cai Minying , Savontaus Eriika , Rinne Petteri
Published: August 2024

Background/objectives

Melanocortins mediate their biological functions via five different melanocortin receptors (MC1R - MC5R). MC1R is expressed in the skin and leukocytes, where it regulates skin pigmentation and inflammatory responses. MC1R is also present in the liver and white adipose tissue, but its functional role in these tissues is unclear. This study aimed at determining the regulatory role of MC1R in fatty acid metabolism.

Methods

Male recessive yellow (Mc1re/e) mice, a model of global MC1R deficiency, and male hepatocyte-specific MC1R deficient mice (Mc1r LKO) were fed a chow or Western diet for 12 weeks. The mouse models were characterized for body weight and composition, liver adiposity, adipose tissue mass and morphology, glucose metabolism and lipid metabolism. Furthermore, qPCR and RNA sequencing analyses were used to investigate gene expression profiles in the liver and adipose tissue. HepG2 cells and primary mouse hepatocytes were used to study the effects of pharmacological MC1R activation.

Results

Chow- and Western diet-fed Mc1re/e showed increased liver weight, white adipose tissue mass and plasma triglyceride (TG) concentration compared to wild type mice. This phenotype occurred without significant changes in food intake, body weight, physical activity or glucose metabolism. Mc1r LKO mice displayed a similar phenotype characterized by larger fat depots, increased adipocyte hypertrophy and enhanced accumulation of TG in the liver and plasma. In terms of gene expression, markers of de novo lipogenesis, inflammation and apoptosis were upregulated in the liver of Mc1r LKO mice, while enzymes regulating lipolysis were downregulated in white adipose tissue of these mice. In cultured hepatocytes, selective activation of MC1R reduced ChREBP expression, which is a central transcription factor for lipogenesis.

Conclusions

Hepatocyte-specific loss of MC1R disturbs fatty acid metabolism in the liver and leads to an obesity phenotype characterized by enhanced adipocyte hypertrophy and TG accumulation in the liver and circulation.
CDK9 inhibition constrains multiple oncogenic transcriptional and epigenetic pathways in prostate cancer
Authors: Rahman Razia , Rahaman Muhammed H. , Hanson Adrienne R. , Choo Nicholas , Xie Jianling , Townley Scott L. , Shrestha Raj , Hassankhani Ramin , Islam Saiful , Ramm Susanne , Simpson Kaylene J. , Risbridger Gail P. , Best Giles , Centenera Margaret M. , Balk Steven P. , Kichenadasse Ganessan , Taylor Renea A. , Butler Lisa M. , Tilley Wayne D. , Conn Simon J. , Lawrence Mitchell G. , Wang Shudong , Selth Luke A.
Published: August 2024

Background

Cyclin-dependent kinase 9 (CDK9) stimulates oncogenic transcriptional pathways in cancer and CDK9 inhibitors have emerged as promising therapeutic candidates.

Methods

The activity of an orally bioavailable CDK9 inhibitor, CDKI-73, was evaluated in prostate cancer cell lines, a xenograft mouse model, and patient-derived tumor explants and organoids. Expression of CDK9 was evaluated in clinical specimens by mining public datasets and immunohistochemistry. Effects of CDKI-73 on prostate cancer cells were determined by cell-based assays, molecular profiling and transcriptomic/epigenomic approaches.

Results

CDKI-73 inhibited proliferation and enhanced cell death in diverse in vitro and in vivo models of androgen receptor (AR)-driven and AR-independent models. Mechanistically, CDKI-73-mediated inhibition of RNA polymerase II serine 2 phosphorylation resulted in reduced expression of BCL-2 anti-apoptotic factors and transcriptional defects. Transcriptomic and epigenomic approaches revealed that CDKI-73 suppressed signaling pathways regulated by AR, MYC, and BRD4, key drivers of dysregulated transcription in prostate cancer, and reprogrammed cancer-associated super-enhancers. These latter findings prompted the evaluation of CDKI-73 with the BRD4 inhibitor AZD5153, a combination that was synergistic in patient-derived organoids and in vivo.

Conclusion

Our work demonstrates that CDK9 inhibition disrupts multiple oncogenic pathways and positions CDKI-73 as a promising therapeutic agent for prostate cancer, particularly aggressive, therapy-resistant subtypes.
Age-related retinal degeneration resulting from the deletion of Shp2 tyrosine phosphatase in photoreceptor neurons
Authors: Rajala Ammaji , Rajala Rahul , Bhat Mohd A. , Eminhizer Mark , Hao Jeff , Du Jianhai , Rajala Raju V. S.
Published: August 2024

Shp2, a critical SH2-domain-containing tyrosine phosphatase, is essential for cellular regulation and implicated in metabolic disruptions, obesity, diabetes, Noonan syndrome, LEOPARD syndrome, and cancers. This study focuses on Shp2 in rod photoreceptor cells, revealing its enrichment, particularly in rods. Deletion of Shp2 in rods leads to age-dependent photoreceptor degeneration. Shp2 targets occludin (OCLN), a tight junction protein, and its deletion reduces OCLN expression in the retina and retinal pigment epithelium (RPE). The isolation of actively translating mRNAs from rods lacking Shp2, followed by RNA sequencing, reveals alterations in cell cycle regulation. Additionally, altered retinal metabolism is observed in retinal cells lacking Shp2. Our studies indicate that Shp2 is crucial for maintaining the structure and function of photoreceptors.
Fetal growth restriction induced by maternal gal-3 deficiency is associated with altered gut-placenta axis
Authors: Xie Yiran , Zhao Fangqi , Wang Yiru , Borowski Sophia , Freitag Nancy , Tirado-Gonzalez Irene , Hofsink Naomi , Matschl Urte , Plösch Torsten , Garcia Mariana G. , Blois Sandra M.
Published: August 2024

Adverse intrauterine conditions may cause fetal growth restriction (FGR), a pregnancy complication frequently linked to perinatal morbidity and mortality. Although many studies have focused on FGR, the pathophysiological processes underlying this disorder are complex and incompletely understood. We have recently determined that galectin-3 (gal-3), a β-galactoside-binding protein, regulates pregnancy-associated processes, including uterine receptibility, maternal vascular adaptation and placentation. Because gal-3 is expressed at both sides of the maternal-fetal interface, we unraveled the contribution of maternal- and paternal-derived gal-3 on fetal-placental development in the prenatal window and its effects on the post-natal period. Deficiency of maternal gal-3 induced maternal gut microbiome dysbiosis, resulting in a sex-specific fetal growth restriction mainly observed in female fetuses and offspring. In addition, poor placental metabolic adaptions (characterized by decreased trophoblast glycogen content and insulin-like growth factor 2 (Igf2) gene hypomethylation) were only associated with a lack of maternal-derived gal-3. Paternal gal-3 deficiency caused compromised vascularization in the placental labyrinth without affecting fetal growth trajectory. Thus, maternal-derived gal-3 may play a key role in fetal-placental development through the gut-placenta axis.
Experimental verification of field-enhanced molecular vibrational scattering at single infrared antennas
Authors: Virmani Divya , Maciel-Escudero Carlos , Hillenbrand Rainer , Schnell Martin
Published: August 2024

Surface-enhanced infrared absorption (SEIRA) spectroscopy exploits the field enhancement near nanophotonic structures for highly sensitive characterization of (bio)molecules. The vibrational signature observed in SEIRA spectra is typically interpreted as field-enhanced molecular absorption. Here, we study molecular vibrations in the near field of single antennas and show that the vibrational signature can be equally well explained by field-enhanced molecular scattering. Although the infrared scattering cross section of molecules is negligible compared to their absorption cross section, the interference between the molecular-scattered field and the incident field enhances the spectral signature caused by molecular vibrational scattering by 10 orders of magnitude, thus becoming as large as that of field-enhanced molecular absorption. We provide experimental evidence that field-enhanced molecular scattering can be measured, scales in intensity with the fourth power of the local field enhancement and fully explains the vibrational signature in SEIRA spectra in both magnitude and line shape. Our work may open new paths for developing highly sensitive SEIRA sensors that exploit the presented scattering concept.
Nivolumab plus platinum-doublet chemotherapy in treatment-naive patients with advanced grade 3 Neuroendocrine Neoplasms of gastroenteropancreatic or unknown origin: The multicenter phase 2 NICE-NEC trial (GETNE-T1913)
Authors: Riesco-Martinez Maria Carmen , Capdevila Jaume , Alonso Vicente , Jimenez-Fonseca Paula , Teule Alex , Grande Enrique , Sevilla Isabel , Benavent Marta , Alonso-Gordoa Teresa , Custodio Ana , Anton-Pascual Beatriz , Hernando Jorge , Polo Eduardo , Castillo-Trujillo Oscar Alfredo , Lamas-Paz Arantza , Teijo Ana , Rodriguez-Gil Yolanda , Soldevilla Beatriz , Garcia-Carbonero Rocio
Published: August 2024

The prognosis of patients with advanced high-grade (G3) digestive neuroendocrine neoplasms (NENs) is rather poor. The addition of immune checkpoint inhibition to platinum-based chemotherapy may improve survival. NICE-NEC (NCT03980925) is a single-arm, phase II trial that recruited chemotherapy-naive, unresectable advanced or metastatic G3 NENs of gastroenteropancreatic (GEP) or unknown origin. Patients received nivolumab 360 mg intravenously (iv) on day 1, carboplatin AUC 5 iv on day 1, and etoposide 100 mg/m2/d iv on days 1–3, every 3 weeks for up to six cycles, followed by nivolumab 480 mg every 4 weeks for up to 24 months, disease progression, death or unacceptable toxicity. The primary endpoint was the 12-month overall survival (OS) rate (H0 50%, H1 72%, β 80%, α 5%). Secondary endpoints were objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and safety. From 2019 to 2021, 37 patients were enrolled. The most common primary sites were the pancreas (37.8%), stomach (16.2%) and colon (10.8%). Twenty-five patients (67.6%) were poorly differentiated carcinomas (NECs) and/or had a Ki67 index >55%. The ORR was 56.8%. Median PFS was 5.7 months (95%CI: 5.1-9) and median OS 13.9 months (95%CI: 8.3-Not reached), with a 12-month OS rate of 54.1% (95%CI: 40.2-72.8) that did not meet the primary endpoint. However, 37.6% of patients were long-term survivors (>2 years). The safety profile was consistent with previous reports. There was one treatment-related death. Nivolumab plus platinum-based chemotherapy was associated with prolonged survival in over one-third of chemonaïve patients with G3 GEP-NENs, with a manageable safety profile.
Assessing global drinking water potential from electricity-free solar water evaporation device
Authors: Zhang Wei , Chen Yongzhe , Ji Qinghua , Fan Yuying , Zhang Gong , Lu Xi , Hu Chengzhi , Liu Huijuan , Qu Jiuhui
Published: August 2024

Universal and equitable access to affordable safely managed drinking water (SMDW) is a significant challenge and is highlighted by the United Nations’ Sustainable Development Goals-6.1. However, SMDW coverage by 2030 is estimated to reach only 81% of the global population. Solar water evaporation (SWE) represents one potential method to ensure decentralized water purification, but its potential for addressing the global SMDW challenge remains unclear. We use a condensation-enhanced strategy and develop a physics-guided machine learning model for assessing the global potential of SWE technology to meet SMDW demand for unserved populations without external electricity input. We find that a condensation-enhanced SWE device (1 m2) can supply enough drinking water (2.5 L day−1) to 95.8% of the population lacking SMDW. SWE can help fulfill universal SMDW coverage by 2030 with an annual cost of 10.4 billion U.S. dollars, saving 66.7% of the current investment and fulfilling the SDG-6.1 goal.
Influence of chirality and sequence in lysine-rich lipopeptide biosurfactants and micellar model colloid systems
Authors: Hamley Ian W. , Adak Anindyasundar , Castelletto Valeria
Published: August 2024

Lipopeptides can self-assemble into diverse nanostructures which can be programmed to incorporate peptide sequences to achieve a remarkable range of bioactivities. Here, the influence of peptide sequence and chirality on micelle structure and interactions is investigated in a series of lipopeptides bearing two lysine or D-lysine residues and tyrosine or tryptophan residues, attached to a hexadecyl lipid chain. All molecules self-assemble into micelles above a critical micelle concentration (CMC). Small-angle x-ray scattering (SAXS) is used to probe micelle shape and structure from the form factor and to probe inter-micellar interactions via analysis of structure factor. The CMC is obtained consistently from surface tension and electrical conductivity measurements. We introduce a method to obtain the zeta potential from the SAXS structure factor which is in good agreement with directly measured values. Atomistic molecular dynamics simulations provide insights into molecular packing and conformation within the lipopeptide micelles which constitute model self-assembling colloidal systems and biomaterials.
Spindle architecture constrains karyotype evolution
Authors: Helsen Jana , Reza Md Hashim , Carvalho Ricardo , Sherlock Gavin , Dey Gautam
Published: August 2024

The eukaryotic cell division machinery must rapidly and reproducibly duplicate and partition the cell’s chromosomes in a carefully coordinated process. However, chromosome numbers vary dramatically between genomes, even on short evolutionary timescales. We sought to understand how the mitotic machinery senses and responds to karyotypic changes by using a series of budding yeast strains in which the native chromosomes have been successively fused. Using a combination of cell biological profiling, genetic engineering and experimental evolution, we show that chromosome fusions are well tolerated up until a critical point. Cells with fewer than five centromeres lack the necessary number of kinetochore-microtubule attachments needed to counter outward forces in the metaphase spindle, triggering the spindle assembly checkpoint and prolonging metaphase. Our findings demonstrate that spindle architecture is a constraining factor for karyotype evolution.
NOX2-TRPM2 coupling promotes Zn2+ inhibition of complex III to exacerbate ROS production in a cellular model of Parkinson’s disease
Authors: AlAhmad Maali , Isbea Hala , Shitaw Esra , Li Fangfang , Sivaprasadarao Asipu
Published: August 2024

Reactive oxygen species (ROS) serve vital physiological functions, but aberrant ROS production contributes to numerous diseases. Unfortunately, therapeutic progress targeting pathogenic ROS has been hindered by the limited understanding of whether the mechanisms driving pathogenic ROS differ from those governing physiological ROS generation. To address this knowledge gap, we utilised a cellular model of Parkinson’s disease (PD), as an exemplar of ROS-associated diseases. We exposed SH-SY5Y neuroblastoma cells to the PD-toxin, MPP+ (1-methyl-4-phenylpyridinium) and studied ROS upregulation leading to cell death, the primary cause of PD. We demonstrate: (1) MPP+ stimulates ROS production by raising cytoplasmic Ca2+ levels, rather than acting directly on mitochondria. (2) To raise the Ca2+, MPP+ co-stimulates NADPH oxidase-2 (NOX2) and the Transient Receptor Potential Melastatin2 (TRPM2) channel that form a positive feedback loop to support each other’s function. (3) Ca2+ exacerbates mitochondrial ROS (mtROS) production not directly, but via Zn2+. (4) Zn2+ promotes electron escape from respiratory complexes, predominantly from complex III, to generate mtROS. These conclusions are drawn from data, wherein inhibition of TRPM2 and NOX2, chelation of Ca2+ and Zn2+, and prevention of electron escape from complexes -all abolished the ability of MPP+ to induce mtROS production and the associated cell death. Furthermore, calcium ionophore mimicked the effects of MPP+, while Zn2+ ionophore replicated the effects of both MPP+ and Ca2+. Thus, we unveil a previously unrecognized signalling circuit involving NOX2, TRPM2, Ca2+, Zn2+, and complex III that drives cytotoxic ROS production. This circuit lies dormant in healthy cells but is triggered by pathogenic insults and could therefore represent a safe therapeutic target for PD and other ROS-linked diseases.
Comprehensive study on the efficiency of vertical bifacial photovoltaic systems: a UK case study
Authors: Badran Ghadeer , Dhimish Mahmoud
Published: August 2024

This paper presents the first comprehensive study of a groundbreaking Vertically Mounted Bifacial Photovoltaic (VBPV) system, marking a significant innovation in solar energy technology. The VBPV system, characterized by its vertical orientation and the use of high-efficiency Heterojunction cells, introduces a novel concept diverging from traditional solar panel installations. Our empirical research, conducted over a full year at the University of York, UK, offers an inaugural assessment of this pioneering technology. The study reveals that the VBPV system significantly outperforms both a vertically mounted monofacial PV (VMPV) system and a conventional tilted monofacial PV (TMPV) system in energy output. Key findings include a daily power output increase of 7.12% and 10.12% over the VMPV system and an impressive 26.91% and 22.88% enhancement over the TMPV system during early morning and late afternoon hours, respectively. Seasonal analysis shows average power gains of 11.42% in spring, 8.13% in summer, 10.94% in autumn, and 12.45% in winter compared to the VMPV system. Against the TMPV system, these gains are even more substantial, peaking at 24.52% in winter. These results underscore the VBPV system's exceptional efficiency in harnessing solar energy across varied environmental conditions, establishing it as a promising and sustainable solution in solar energy technology.
Improving the acoustic performance of flexible polyurethane foam using biochar modified by (3-aminopropyl)trimethoxysilane coupling agent
Authors: Maamoun Ahmed Abdelhamid , Abouomar Ramadan M. , El-Basheer Tarek M. , Azab Mostafa A. , Zaki ElSayed G. , Elsaeed Shymaa M. , Elkhateeb Ahmed
Published: August 2024

This study aims to investigate the potential of integrating natural biochar (BC) derived from eggshell waste into flexible polyurethane (FPU) foam to enhance its mechanical and acoustic performance. The study explores the impact of incorporating BC at various weight ratios (0.1, 0.3, 0.5, and 0.7 wt. %) on the properties of the FPU foam. Additionally, the effects of modifying the BC with (3-aminopropyl)trimethoxysilane (APTMS) at different ratios (10, 20, and 30 wt. %) and the influence of diverse particle sizes of BC on the thermal, mechanical, and acoustic characteristics of the FPU composite are investigated. The functional groups, morphology, and elemental composition of the developed FPU composites are analyzed using Fourier-transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (FESEM), and energy-dispersive X-ray (EDX) techniques. Characteristics such as density, gel fraction, and porosity were also assessed. The results reveal that the density of FPU foam increased by 4.32% and 7.83% while the porosity decreased to 50.22% and 47.05% with the addition of 0.1 wt. % of unmodified BC and modified BC with 20 wt. % APTMS, respectively, compared to unfilled FPU. Additionally, the gel fraction of the FPU matrix increases by 1.91% and 3.55% with the inclusion of 0.1 wt. % unmodified BC and modified BC with 20 wt. % APTMS, respectively. Furthermore, TGA analysis revealed that all FPU composites demonstrate improved thermal stability compared to unfilled FPU, reaching a peak value of 312.17°C for the FPU sample incorporating BC modified with 20 wt. % APTMS. Compression strength increased with 0.1 wt. % untreated BC but decreased at higher concentrations. Modifying BC with 20% APTMS resulted in an 8.23% increase in compressive strength compared to unfilled FPU. Acoustic analysis showed that the addition of BC improved absorption, and modified BC enhanced absorption characteristics of FPU, reaching Class D with a 20 mm thickness. BC modified with APTMS further improved acoustic properties compared to the unfilled FPU sample (Class E), with 20% modification showing the best results. These composites present promising materials for sound absorption applications and address environmental issues related to eggshell waste.
How boots affect the kinematics and kinetics of lower limb joints during walking compared to casual footwear
Authors: Haghighat Farzaneh , Rezaie Mohammadreza , Majlesi Mahdi
Published: August 2024

Boots are widely used by many people for various purposes, but their impact on gait biomechanics and injury risk is not well understood. This study investigated the effects of boots on walking biomechanics, compared to casual footwear. The lower limb joint kinematics and kinetics of 20 healthy male participants aged 20 to 30 years old were compared during self-paced walking with boots and shoes. The results showed that walking with boots is associated with greater hip extensor (P = 0.009) and ankle dorsiflexor (P < 0.001) moments in early stance, hip power generation (P < 0.001) and knee power absorption (P < 0.001) in early swing phase, hip abductor (P < 0.001) and knee adduction (P < 0.001) moments in the entire stance, net concentric work for the hip joint in sagittal (13.9%, P = 0.001) and frontal (21.7%, P = 0.002) planes. In contrast, the subtalar supinator moment in the entire stance (P < 0.001), ankle angular velocity in late stance (P < 0.001), and net concentric (− 42.7%, P < 0.001) and eccentric (− 44.6%, P = 0.004) works of subtalar joint were significantly lower in the boot condition. The compensatory adjustments in the hip and knee joints may result from ankle restrictions. While boots may aid those with ankle disorders, lower limb loading and the risk of musculoskeletal injuries and osteoarthritis could be increased. This study offers new perspectives on the biomechanical impact of boots on gait, potential prevention and treatment strategies of related injuries, and advancing footwear design.