bluuebunny/crossref_metadata_2025 huggingface dataset:
Raman and autofluorescence spectroscopy for in situ identification of neoplastic tissue during surgical treatment of brain tumors
Authors: Uckermann Ortrud , Ziegler Jonathan , Meinhardt Matthias , Richter Sven , Schackert Gabriele , Eyüpoglu Ilker Y. , Hijazi Mido M. , Krex Dietmar , Juratli Tareq A. , Sobottka Stephan B. , Galli Roberta
Published: August 2024

Purpose

Raman spectroscopy (RS) is a promising method for brain tumor detection. Near-infrared autofluorescence (AF) acquired during RS provides additional useful information for tumor identification and was investigated in comparison with RS for delineating brain tumors in situ.

Methods

Raman spectra were acquired together with AF in situ within the solid tumor and at the tumor border during routine brain tumor surgeries (218 spectra; glioma WHO II-III, n = 6; GBM, n = 10; metastases, n = 10; meningioma, n = 3). Tissue classification for tumor identification in situ was trained on ex vivo data (375 spectra; glioma/GBM patients, n = 20; metastases, n = 11; meningioma, n = 13; and epileptic hippocampi, n = 4).

Results

Both in situ and ex vivo data showed that AF intensity in brain tumors was lower than that in border regions and normal brain tissue. Moreover, a positive correlation was observed between the AF intensity and the intensity of the Raman band corresponding to lipids at 1437 cm− 1, while a negative correlation was found with the intensity of the protein band at 1260 cm− 1. The classification of in situ AF and RS datasets matched the surgeon’s evaluation of tissue type, with correct rates of 0.83 and 0.84, respectively. Similar correct rates were achieved in comparison to histopathology of tissue biopsies resected in selected measurement positions (AF: 0.80, RS: 0.83).

Conclusions

Spectroscopy was successfully integrated into existing neurosurgical workflows, and in situ spectroscopic data could be classified based on ex vivo data. RS confirmed its ability to detect brain tumors, while AF emerged as a competitive method for intraoperative tumor delineation.
Linearity of the Co-moving Velocity
Authors: Hansen Alex
Published: August 2024

The co-moving velocity is a new variable in the description of immiscible two-phase flow in porous media. It is the saturation-weighted average over the derivatives of the seepage velocities of the two immiscible fluids with respect to saturation. Based on analysis of relative permeability data and computational modeling, it has been proposed that the co-moving velocity is linear when plotted against the derivative of the average seepage velocity with respect to the saturation, the flow derivative. I show here that it is enough to demand that the co-moving velocity is characterized by an additive parameter in addition to the flow derivative to be linear. This has profound consequences for relative permeability theory as it leads to a differential equation relating the two relative permeabilities describing the flow. I present this equation together with two solutions.
Exploring multiple phases and first-order phase transitions in Kármán Vortex Street
Authors: Li Xu , Xiang Xing , Xue Tingting , Wang Limin , Chen Xiaosong
Published: August 2024

Kármán Vortex Street, a fascinating phenomenon of fluid dynamics, has intrigued the scientific community for a long time. Many researchers have dedicated their efforts to unraveling the essence of this intriguing flow pattern. Here, we apply the lattice Boltzmann method with curved boundary conditions to simulate flows around a circular cylinder and study the emergence of Kármán Vortex Street using the eigen microstate approach, which can identify phase transition and its order-parameter. At low Reynolds number, there is only one dominant eigen microstate W1 of laminar flow. At Re
c
1
= 53.6, there is a phase transition with the emergence of an eigen microstate pair W2,3 of pressure and velocity fields. Further at Re
c
2
. = 56, there is another phase transition with the emergence of two eigen microstate pairs W4,5 and W6,7. Using the renormalization group theory of eigen microstate, both phase transitions are determined to be first-order. The two-dimensional energy spectrum of eigen microstate for W1, W2,3 after Rec
1, W4–7 after Re
c
2
exhibit −5/3 power-law behavior of Kolnogorov’s K41 theory. These results reveal the complexity and provide an analysis of the Kármán Vortex Street from the perspective of phase transitions.
Assessment of groundwater quality using hydrochemical process, GIS and multivariate statistical analysis at central Rif, North Morocco
Authors: Benyoussef Said , Arabi Mourad , El Yousfi Yassine , Makkaoui Mohamed , Gueddari Hicham , El Ouarghi Hossain , Abdaoui Abdellali , Ghalit Mohammad , Zegzouti Younes Filali , Azirar Maryam , Himi Mahjoub , Alitane Abdennabi , Chahban Mohamed , Boughrous Ali Ait
Published: August 2024

This study investigated groundwater in the central Rif region of northern Morocco by analysing 55 water sampling points to assess its physicochemical and hydrogeochemical properties. Through hydrochemical analysis, GIS spatial exploration, and multivariate statistical analysis, a direct correlation was found between EC, TDS, and major ions, influencing overall water mineralization. The key findings included pH levels ranging from 6.10 to 8.52, EC from 828 to 4581 μS/cm, and varying concentrations of Ca2+, Mg2+, Na+, K+, HCO2–, Cl–, N–NO2–, and SO42–. Notably, TDS and TH ranged from 647.19–3609.36 mg/L and 64.23–1051.24 mg/L, respectively, with a significant portion of samples exceeding WHO guidelines, particularly chloride (61.81%), sulfate (92.72%), and nitrate (12.72%) samples. The Piper diagram highlights sodium chlorides (Na–Cl) as the predominant chemical facies (70.9%), while the Gibbs diagram emphasizes the impact of evaporation on water chemistry dynamics. This study revealed the complex influence of geological and anthropogenic factors on groundwater quality, potentially leading to seawater intrusion in coastal aquifers. The observed high mineralization and hardness levels, in addition to mild alkalinity, pose public health risks, underscoring the need for continuous monitoring and sustainable management practices in coastal groundwater management to protect human health and the environment.
The Moral Turing Test: a defense
Authors: Bohn Einar Duenger
Published: August 2024

In this paper, I raise the question whether an artificial intelligence can act morally. I first sketch and defend a general picture of what is at stake in this question. I then sketch and defend a behavioral test, known as the Moral Turing Test, as a good sufficiency test for an artificial intelligence acting morally. I end by discussing some general anticipated objections.
Multimodal music datasets? Challenges and future goals in music processing
Authors: Christodoulou Anna-Maria , Lartillot Olivier , Jensenius Alexander Refsum
Published: August 2024

The term “multimodal music dataset” is often used to describe music-related datasets that represent music as a multimedia art form and multimodal experience. However, the term “multimodality” is often used differently in disciplines such as musicology, music psychology, and music technology. This paper proposes a definition of multimodality that works across different music disciplines. Many challenges are related to constructing, evaluating, and using multimodal music datasets. We provide a task-based categorization of multimodal datasets and suggest guidelines for their development. Diverse data pre-processing methods are illuminated, highlighting their contributions to transparent and reproducible music analysis. Additionally, evaluation metrics, methods, and benchmarks tailored for multimodal music processing tasks are scrutinized, empowering researchers to make informed decisions and facilitating cross-study comparisons.
Predictive modelling of metabolic syndrome in Ghanaian diabetic patients: an ensemble machine learning approach
Authors: Acheampong Emmanuel , Adua Eric , Obirikorang Christian , Anto Enoch Odame , Peprah-Yamoah Emmanuel , Obirikorang Yaa , Asamoah Evans Adu , Opoku-Yamoah Victor , Nyantakyi Michael , Taylor John , Buckman Tonnies Abeku , Yakubu Maryam , Afrifa-Yamoah Ebenezer
Published: August 2024

Objectives

The burgeoning prevalence of cardiometabolic disorders, including type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) within Africa is concerning. Machine learning (ML) techniques offer a unique opportunity to leverage data-driven insights and construct predictive models for MetS risk, thereby enhancing the implementation of personalised prevention strategies. In this work, we employed ML techniques to develop predictive models for pre-MetS and MetS among diabetic patients.

Methods

This multi-centre cross-sectional study comprised of 919 T2DM patients. Age, gender, novel anthropometric indices along with biochemical measures were analysed using BORUTA feature selection and an ensemble majority voting classification model, which included logistic regression, k-nearest neighbour, Gaussian Naive Bayes, Gradient boosting classification, and support vector machine.

Results

Distinct metabolic profiles and phenotype clusters were associated with MetS progression. The BORUTA algorithm identified 10 and 16 significant features for pre-MetS and MetS prediction, respectively. For pre-MetS, the top-ranked features were lipid accumulation product (LAP), triglyceride-glucose index adjusted for waist-to-height ratio (TyG-WHtR), coronary risk (CR), visceral adiposity index (VAI) and abdominal volume index (AVI). For MetS prediction, the most influential features were VAI, LAP, waist triglyceride index (WTI), Very low-density cholesterol (VLDLC) and TyG-WHtR. Majority voting ensemble classifier demonstrated superior performance in predicting pre-MetS (AUC = 0.79) and MetS (AUC = 0.87).

Conclusion

Identifying these risk factors reveals the complex interplay between visceral adiposity and metabolic dysregulation in African populations, enabling early detection and treatment. Ethical integration of ML algorithms in clinical decision-making can streamline identification of high-risk individuals, optimize resource allocation, and enable precise, tailored interventions.
Mathematical modeling of Ebola using delay differential equations
Authors: Raza Ali , Ahmed Nauman , Rafiq Muhammad , Akgül Ali , Cordero Alicia , Torregrosa Juan R.
Published: August 2024

Nonlinear delay differential equations (NDDEs) are essential in mathematical epidemiology, computational mathematics, sciences, etc. In this research paper, we have presented a delayed mathematical model of the Ebola virus to analyze its transmission dynamics in the human population. The delayed Ebola model is based on the four human compartments susceptible, exposed, infected, and recovered (SEIR). A time-delayed technique is used to slow down the dynamics of the host population. Two significant stages are analyzed in the said model: Ebola-free equilibrium (EFE) and Ebola-existing equilibrium (EEE). Also, the reproduction number of a model with the sensitivity of parameters is studied. Furthermore, the local asymptotical stability (LAS) and global asymptotical stability (GAS) around the two stages are studied rigorously using the Jacobian matrix Routh–Hurwitz criterion strategies for stability and Lyapunov function stability. The delay effect has been observed in the model in inverse relation of susceptible and infected humans (it means the increase of delay tactics that the susceptibility of humans increases and the infectivity of humans decreases eventually approaches zero which means that Ebola has been controlled into the population). For the numerical results, the Euler method is designed for the system of delay differential equations (DDEs) to verify the results with an analytical model analysis.
Characterization and differences of acoustic signals response of semi-circular red sandstone under combined monotonous and cyclic loadings
Authors: Zou Quanle , Chen Chunmei , Chen Zihan , Peng Kang , Lv Hong , Zhan Jinfei
Published: August 2024

After underground coal mining, rocks are often subjected to tensile damage by the interaction of dynamic and static loadings. The process of rock fracture development under dynamic and static loadings will be released in the form of acoustic energy to form an acoustic signal. In addition, the acoustic signals in dynamic loading differ from that in static loading. Therefore, this study conducted three-point bending experiments with continuous dynamic loading and dynamic–static coupling loading on semi-circular red sandstone specimens. The acoustic signals during red sandstone specimens’ tensile damage were monitored in real-time. The results show that red sandstone’s tensile strength and deformation are enhanced under dynamic–static coupling loading. The red sandstone has a more effective acoustic emission hit rate, energy rate, and r during tensile damage under continuous dynamic loading. In dynamic loading, macroscopic fractures are developed in red sandstone, which has few acoustic emission events but releases strong acoustic signals. In static loading, the pores inside the red sandstone are compacted, the rock particles are rearranged, and the tiny fractures are closed, and its acoustic emission events are many but low in energy. In addition, the rock particles in the front area of the static loading fracture are tightly cemented, which increases the difficulty of separating the rock particles in the front area of the fracture under dynamic loading. Then weakening the red sandstone fracture development process and suppressing its acoustic signals. The research results provide more insight into the differences in tensile damage processes in red sandstone under the interaction of dynamic and static loadings.
On the interpretability of quantum neural networks
Authors: Pira Lirandë , Ferrie Chris
Published: August 2024

Interpretability of artificial intelligence (AI) methods, particularly deep neural networks, is of great interest. This heightened focus stems from the widespread use of AI-backed systems. These systems, often relying on intricate neural architectures, can exhibit behavior that is challenging to explain and comprehend. The interpretability of such models is a crucial component of building trusted systems. Many methods exist to approach this problem, but they do not apply straightforwardly to the quantum setting. Here, we explore the interpretability of quantum neural networks using local model-agnostic interpretability measures commonly utilized for classical neural networks. Following this analysis, we generalize a classical technique called LIME, introducing Q-LIME, which produces explanations of quantum neural networks. A feature of our explanations is the delineation of the region in which data samples have been given a random label, likely subjects of inherently random quantum measurements. We view this as a step toward understanding how to build responsible and accountable quantum AI models.
Stability analysis for the anisotropic curve shortening flow of planar networks
Authors: Gößwein Michael , Novaga Matteo , Pozzi Paola
Published: August 2024

In this article we consider the anisotropic curve shortening flow for a planar network of three curves which meet at a triple junction. We show that the anisotropic energy fulfills a Łojasiewicz–Simon gradient inequality from which we derive a stability result for the evolution. Precisely, we show that, for initial data which are close to the energy minimizer, the flow exists globally and converges to the minimizer.
The Problematisation of Young People Within Existing Housing-Related Policy in Queensland
Authors: Keen Lilly , Newcomb Michelle
Published: August 2024

More young people are experiencing homelessness and housing stress in Australia than ever before, with policy responses failing to address a current housing and cost-of-living crisis. Of particular concern when considering increasing rates of youth homelessness and housing stress is the absence of research examining existing policy. This research was undertaken in the Australian state of Queensland and contributes to addressing this gap in knowledge by utilising Carol Bacchi’s (2009) ‘What’s the Problem Represented to be?’ approach to policy analysis to examine three state policies, namely Towards Ending Homelessness for Young Queenslanders 2022–2027, the Queensland Housing Strategy 2017–2027, and the Queensland Youth Strategy. A range of discourses were found which position young people as lacking knowledge and skills to obtain housing. Emphasis is also placed on education, training, and employment as solutions to youth housing issues rather than a genuine focus on empowering young people through policy and practice initiatives. The findings of this research mirror existing discourses found in global conversations about youth homelessness and housing stress and contribute to a growing knowledge base around the importance of engaging young people in decision making within public policy and social reform.
Associations of hair cortisol levels with violence, poor mental health, and harmful alcohol and other substance use among female sex workers in Nairobi, Kenya
Authors: Panneh Mamtuti , Ding Qingming , Kabuti Rhoda ,   The Maisha Fiti study champions, Bradley John , Ngurukiri Polly , Kungu Mary , Abramsky Tanya , Pollock James , Beksinska Alicja , Shah Pooja , Irungu Erastus , Gafos Mitzy , Seeley Janet , Weiss Helen A. , Elzagallaai Abdelbaset A. , Rieder Michael J. , Kaul Rupert , Kimani Joshua , Beattie Tara
Published: August 2024

Violence, poor mental health, and harmful substance use are commonly experienced by female sex workers (FSWs) in sub-Saharan Africa, all of which are associated with increased HIV susceptibility. We aimed to investigate the associations between violence, poor mental health and harmful alcohol/substance use with hair cortisol concentration (HCC) levels as a potential biological pathway linking the experiences of these stressors and HIV vulnerability. We used the baseline data of the Maisha Fiti study of FSWs in Nairobi, Kenya. Participants reported recent violence, poor mental health, and harmful alcohol/substance use. Hair samples proximal to the scalp were collected to measure cortisol levels determined by ELISA. We analysed the data of 425 HIV-negative respondents who provided at least 2 cm of hair sample. The prevalence of recent violence was 89.3% (physical 54.6%; sexual 49.4%; emotional 77.0% and financial 66.5%), and 29.1% had been arrested due to sex work. 23.7% of participants reported moderate/severe depression, 11.6% moderate/severe anxiety, 13.5% PTSD and 10.8% recent suicidal thoughts and/or attempts. About half of the participants (48.8%) reported recent harmful alcohol and/or other substance use. In multivariable linear regression analyses, both physical and/or sexual violence (adjusted geometric mean ratio (aGMR) = 1.28; 95% CI 1.01–1.62) and harmful alcohol and/or other substance use (aGMR = 1.31; 95% CI 1.03–1.65) were positively and independently associated with increased HCC levels. Findings suggest a role of violence and substance use in elevated HCC levels, which could increase HIV risk due to cortisol-related T cell activation. However, longitudinal and mechanistic studies are needed to confirm this hypothesis.
THINKING ALOUD: THE SOLILOQUY CYCLE
Authors: Simaku Thomas
Published: August 2024

Beginning with Soliloquy I for solo violin in 1998, the author has been engaged in creating a series of highly virtuosic solo pieces for various instruments. Each piece presents a different character, yet all are framed by a single protagonist who narrates in different languages.

This article focuses particularly on analyses of Soliloquies II, VI, VII, VIII and IX, but also offers a discussion of the genesis of and processes involved in the whole cycle, which now embraces instruments from every section of the orchestra; the most recent, Soliloquy IX, for solo trumpet, was written in 2022. The suitability of the title Soliloquy is also considered; this article in turn could itself be considered a soliloquy.
PROPORTION AND SYMMETRY AS MUTUAL ANTAGONISTS IN TUNING: SOME QUARTER-TONE RESOURCES
Authors: Bates Joe
Published: August 2024

Quarter-tones have the dubious honour of being the microtonal default in Western art music, yet they have been of little recent interest to those most involved with extended intonation. Other microtonal equal divisions have appealed as pragmatic approximations of consonant just-intonation intervals, something that quarter-tones do not offer. This article proposes that quarter-tones can be valued in a different way, for their ability to generate symmetrical harmonic resources that divide the fourth and fifth as the tritone does the octave. These resources are offered as examples of a broader aesthetic of symmetry, which is contrasted with an aesthetic of proportion. These antagonistic principles are explored through the case of the ever problematic tritone, illustrating how proportion and symmetry are best understood using the symbolic resources of just intonation and equal temperament respectively. Drawing on the work of Robert Hasegawa, Georg Friedrich Haas and Ivan Wyschnegradsky, the article argues for a hybrid approach that embraces both just intonation and equal temperament.
HABITUS, RESISTANCE AND THE PRODUCTION OF MUSICAL MEANING
Authors: Dell Niamh
Published: August 2024

This article defines and explores the concept of ‘resistance’ as a source of musical meaning in performance. Using Pierre Bourdieu's concept of ‘habitus’ as a framework, I examine my musical habitus: the embodied, internalised ways I play my instrument and think about music, which reflect my extensive musical histories and the fields in which these histories have taken place. Resistance arises in practice when this habitus is undermined. When the types of musicking undertaken circumvent my habituated understanding of acceptable performance and performative roles, it manifests as a pull towards more familiar modes of musical engagement. Making specific reference to resistance experienced in the development and performance of Alex Harker's Drift Shadow (2021), for solo oboe and electronics, the article outlines the ways in which my subjective relationship to my instrument and my role as a performer produce particular understandings of a work that can then nuance the way I play the piece.
Gesundheit von Pflegenden während der COVID-19-Pandemie in der Schweiz
Authors: Huber Claudia , Schorro Ewald , Hofstetter-Hefti Gabriela , Jubin Jonathan , Delmas Philippe , Bachmann Annie Oulevey , Gilles Ingrid , Bucher Claudia Ortoleva
Published: August 2024

Zusammenfassung: Hintergrund: Die COVID-19-Pandemie hatte erhebliche Auswirkungen auf die Gesundheitsversorgung. Pflegende spielten eine entscheidende Rolle zur Bewältigung der Krise. Ziel: Zielsetzung der Studie ist die Untersuchung des physischen und psychischen Gesundheitszustands sowie der Ressourcen von diplomierten Pflegenden während der Pandemie. Methoden: In einer gesamtschweizerisch durchgeführten Längsschnittstudie mit Mixed Methods Design erfolgte die Datenerhebung bei Pflegenden in Deutschschweizer Akutspitälern zwischen 2021 und 2022 durch Fragebogenerhebungen und Fokusgruppen-Interviews. Die Daten wurden mit multipler Regressionsanalyse sowie Knowledge-Mapping und Neuman-System-Modell ausgewertet. Ergebnisse: Die Ergebnisse zeigen, dass sich die Gesundheit, Lebensqualität und Zufriedenheit am Arbeitsplatz verbessern und der Stress abnimmt. Dabei sind beeinflussende extrapersonelle Faktoren, beispielsweise Reorganisationen mit aktivem Einbezug von Pflegenden. Auf der interpersonellen Ebene ist etwa die Unterstützung durch Vorgesetzte oder Kolleginnen und Kollegen hilfreich. Auf der intrapersonellen Ebene war unter anderem die Anerkennung der Fähigkeiten der Pflegenden wichtig, um während der Dauer der COVID-19-Pandemie gesund zu bleiben. Schlussfolgerungen: Entscheidend ist, vermehrte Wertschätzung, Partizipation, Ausbildungs- und Karrieremöglichkeiten sowie flexible Arbeitsmodelle für eine nachhaltige Verbesserung der Situation, welche sich schlussendlich auf Gesundheit und Wohlbefinden der Pflegenden auswirkt, langfristig in die Gesundheitsversorgung zu integrieren.
Microbial Metabolism and Environmental Controls of Acetate Cycling in the Northwest Pacific Ocean
Authors: Mao Shi‐Hai , Zhou Zhen , Yan Shi‐Bo , Xu Gao‐Bin , Li Xiao‐Jun , Zhang Hong‐Hai , Yang Gui‐Peng , Zhuang Guang‐Chao
Published: August 2024

Microbial acetate metabolism is an important part of marine carbon cycling. We present a comprehensive study to constrain microbial acetate metabolism and its regulation in surface seawater of the northwest Pacific Ocean. We found that acetate oxidation (rate constant k: 0.016–0.506 day−1) accounted for 77.6%–99.4% of the total microbial acetate uptake, suggesting that acetate was predominantly used as a microbial energy source. Acetate also served as a significant biomass carbon source, as reflected by the elevated contribution of acetate assimilation to bacterial carbon production. Acetate turnover was largely influenced by water mass mixing and nutrient conditions. Atmospheric deposition was a source of acetate in surface water and this process can also impact the microbial acetate uptake. Microbial utilization of acetate could account for up to 25.9% of the bacterial carbon demand, suggesting the significant role of acetate metabolism in microbial carbon cycling in the open ocean.
Rheology and Structure of Model Smectite Clay: Insights From Molecular Dynamics
Authors: Lin Z.‐Y. , Hatano T.
Published: August 2024

The low frictional strength of smectite minerals, such as montmorillonite, is thought to play a critical role in controlling the rheology and the stability of clay‐rich faults. In this study, we perform molecular dynamics simulations on a model clay system. Clay platelets are simplified as oblate ellipsoids interacting via the Gay‐Berne potential. We study the rheology and structural development during shear in this model system, which is sheared at constant strain rates for 10 strains after compression and equilibrium. We find that the system exhibits velocity‐strengthening behavior over a range of normal stresses from 1.68 to 56.18 MPa and a range of strain rates from 6.93 × 105 to 6.93 × 108/s. The relationship between shear stress and strain rate follows the Herschel‐Bulkley model. Shear localization is observed at lower strain rates despite the velocity‐strengthening friction, while homogeneous shear is realized at higher strain rates. The structure change due to shear is analyzed from various aspects: the porosity, particle orientation, velocity profile, and the parallel radial distribution function. We find that particle rearrangement and compaction dominate at the early stage of shear when the shear stress increases. The shear band starts to form in the later stage as the shear stress decreases and relaxes to a steady‐state value. The structural development at low strain rates is similar to previous experimental observations. The stacking structure is reduced during shear and restores logarithmically with time in the rest period.
B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation
Authors: Pfeuffer Lisa , Siegert Viola , Frede Julia , Rieger Leonie , Trozzo Riccardo , de Andrade Krätzig Niklas , Ring Sandra , Sarhadi Shamim , Beck Nicole , Niedermeier Stefan , Abril-Gil Mar , Elbahloul Mohamed , Remke Marianne , Steiger Katja , Eichner Ruth , Jellusova Julia , Rad Roland , Bassermann Florian , Winter Christof , Ruland Jürgen , Buchner Maike
Published: August 2024

B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), remain incurable, with MM particularly prone to relapse. Our study introduces a novel mouse model with active RANK signaling and the TCL1 oncogene, displaying both CLL and MM phenotypes. In younger mice, TCL1 and RANK expression expands CLL-like B1-lymphocytes, while MM originates from B2-cells, becoming predominant in later stages and leading to severe disease progression and mortality. The induced MM mimics human disease, exhibiting features like clonal plasma cell expansion, paraproteinemia, anemia, and kidney and bone failure, as well as critical immunosurveillance strategies that promote a tumor-supportive microenvironment. This research elucidates the differential impacts of RANK activation in B1- and B2-cells and underscores the distinct roles of single versus combined oncogenes in B-cell malignancies. We also demonstrate that human MM cells express RANK and that inhibiting RANK signaling can reduce MM progression in a xenotransplantation model. Our study provides a rationale for further investigating the effects of RANK signaling in B-cell transformation and the shaping of a tumor-promoting microenvironment.
Osteoclasts control endochondral ossification via regulating acetyl-CoA availability
Authors: Deng Daizhao , Liu Xianming , Huang Wenlan , Yuan Sirui , Liu Genming , Ai Shanshan , Fu Yijie , Xu Haokun , Zhang Xinyi , Li Shihai , Xu Song , Bai Xiaochun , Zhang Yue
Published: August 2024

Osteoclast is critical in skeletal development and fracture healing, yet the impact and underlying mechanisms of their metabolic state on these processes remain unclear. Here, by using osteoclast-specific small GTPase Rheb1-knockout mice, we reveal that mitochondrial respiration, rather than glycolysis, is essential for cathepsin K (CTSK) production in osteoclasts and is regulated by Rheb1 in a mechanistic target of rapamycin complex 1 (mTORC1)-independent manner. Mechanistically, we find that Rheb1 coordinates with mitochondrial acetyl-CoA generation to fuel CTSK, and acetyl-CoA availability in osteoclasts is the central to elevating CTSK. Importantly, our findings demonstrate that the regulation of CTSK by acetyl-CoA availability is critical and may confer a risk for abnormal endochondral ossification, which may be the main cause of poor fracture healing on alcohol consumption, targeting Rheb1 could successfully against the process. These findings uncover a pivotal role of mitochondria in osteoclasts and provide a potent therapeutic opportunity in bone disorders.
LncRNA HAGLROS promotes breast cancer evolution through miR-135b-3p/COL10A1 axis and exosome-mediated macrophage M2 polarization
Authors: Meng Ziqi , Zhang Rui , Wu Xuwei , Piao Zhengri , Zhang Meihua , Jin Tiefeng
Published: August 2024

Long non-coding RNAs (lncRNAs) play an important role in breast cancer progression, but the function of lncRNAs in regulating tumor-associated macrophages (TAMs) remains unclear. As carriers of lncRNAs, exosomes play an important role as mediators in the communication between cancer cells and the tumor microenvironment. In this study, we found that lncRNA HAGLROS was highly expressed in breast cancer tissues and plasma exosomes, and its high expression was related to the poor prognosis of breast cancer patients. Functionally, breast cancer cell-derived exosomal lncRNA HAGLROS promotes breast cancer cell proliferation, migration, epithelial-mesenchymal transition (EMT) process and angiogenesis by inducing TAM/M2 polarization. Mechanistically, lncRNA HAGLROS competitively binds to miR-135-3p to prevent the degradation of its target gene COL10A1. Collectively, these results indicated that the lncRNA HAGLROS/miR-135b-3p/COL10A1 axis promoted breast cancer progression, and revealed the interactive communication mechanism between breast cancer cells and TAMs, suggesting that lncRNA HAGLROS may be a potential biomarker and therapeutic target for breast cancer.
Premature senescence is regulated by crosstalk among TFEB, the autophagy lysosomal pathway and ROS derived from damaged mitochondria in NaAsO2-exposed auditory cells
Authors: Suzuki Yuna , Hayashi Ken , Goto Fumiyuki , Nomura Yasuyuki , Fujimoto Chisato , Makishima Makoto
Published: August 2024

Age-related hearing loss (ARHL) is one of the most prevalent types of sensory decline in a superaging society. Although various studies have focused on the effect of oxidative stress on the inner ear as an inducer of ARHL, there are no effective preventive approaches for ARHL. Recent studies have suggested that oxidative stress-induced DNA damage responses (oxidative DDRs) drive cochlear cell senescence and contribute to accelerated ARHL, and autophagy could function as a defense mechanism against cellular senescence in auditory cells. However, the underlying mechanism remains unclear. Sodium arsenite (NaAsO2) is a unique oxidative stress inducer associated with reactive oxygen species (ROS) that causes high-tone hearing loss similar to ARHL. Transcription factor EB (TFEB) functions as a master regulator of the autophagy‒lysosome pathway (ALP), which is a potential target during aging and the pathogenesis of various age-related diseases. Here, we focused on the function of TFEB and the impact of intracellular ROS as a potential target for ARHL treatment in a NaAsO2-induced auditory premature senescence model. Our results suggested that short exposure to NaAsO2 leads to DNA damage, lysosomal damage and mitochondrial damage in auditory cells, triggering temporary signals for TFEB transport into the nucleus and, as a result, causing insufficient autophagic flux and declines in lysosomal function and biogenesis and mitochondrial quality. Then, intracellular ROS derived from damaged mitochondria play a role as a second messenger to induce premature senescence in auditory cells. These findings suggest that TFEB activation via transport into the nucleus contributes to anti-senescence activity in auditory cells and represents a new therapeutic target for ARHL. We have revealed the potential function of TFEB as a master regulator of the induction of oxidative stress-induced premature senescence and the senescence-associated secretion phenotype (SASP) in auditory cells, which regulates ALP and controls mitochondrial quality through ROS production.
Distinct roles of monkey OFC-subcortical pathways in adaptive behavior
Authors: Oyama Kei , Majima Kei , Nagai Yuji , Hori Yukiko , Hirabayashi Toshiyuki , Eldridge Mark A. G. , Mimura Koki , Miyakawa Naohisa , Fujimoto Atsushi , Hori Yuki , Iwaoki Haruhiko , Inoue Ken-ichi , Saunders Richard C. , Takada Masahiko , Yahata Noriaki , Higuchi Makoto , Richmond Barry J. , Minamimoto Takafumi
Published: August 2024

Primates must adapt to changing environments by optimizing their behavior to make beneficial choices. At the core of adaptive behavior is the orbitofrontal cortex (OFC) of the brain, which updates choice value through direct experience or knowledge-based inference. Here, we identify distinct neural circuitry underlying these two separate abilities. We designed two behavioral tasks in which two male macaque monkeys updated the values of certain items, either by directly experiencing changes in stimulus-reward associations, or by inferring the value of unexperienced items based on the task’s rules. Chemogenetic silencing of bilateral OFC combined with mathematical model-fitting analysis revealed that monkey OFC is involved in updating item value based on both experience and inference. In vivo imaging of chemogenetic receptors by positron emission tomography allowed us to map projections from the OFC to the rostromedial caudate nucleus (rmCD) and the medial part of the mediodorsal thalamus (MDm). Chemogenetic silencing of the OFC-rmCD pathway impaired experience-based value updating, while silencing the OFC-MDm pathway impaired inference-based value updating. Our results thus demonstrate dissociable contributions of distinct OFC projections to different behavioral strategies, and provide new insights into the neural basis of value-based adaptive decision-making in primates.
A consistent budgeting of terrestrial carbon fluxes
Authors: Dorgeist Lea , Schwingshackl Clemens , Bultan Selma , Pongratz Julia
Published: August 2024

Accurate estimates of CO2 emissions from anthropogenic land-use change (ELUC) and of the natural terrestrial CO2 sink (SLAND) are crucial to precisely know how much CO2 can still be emitted to meet the goals of the Paris Agreement. In current carbon budgets, ELUC and SLAND stem from two model families that differ in how CO2 fluxes are attributed to environmental and land-use changes, making their estimates conceptually inconsistent. Here we provide consistent estimates of ELUC and SLAND by integrating environmental effects on land carbon into a spatially explicit bookkeeping model. We find that state-of-the-art process-based models overestimate SLAND by 23% (min: 8%, max: 33%) in 2012–2021, as they include hypothetical sinks that in reality are lost through historical ecosystem degradation. Additionally, ELUC increases by 14% (8%, 23%) in 2012–2021 when considering environmental effects. Altogether, we find a weaker net land sink, which makes reaching carbon neutrality even more ambitious. These results highlight that a consistent estimation of terrestrial carbon fluxes is essential to assess the progress of net-zero emission commitments and the remaining carbon budget.
A temperature sensor with a wide spectral range based on a dual-emissive TADF dendrimer system
Authors: Si Changfeng , Wang Tao , Xu Yan , Lin Dongqing , Sun Dianming , Zysman-Colman Eli
Published: August 2024

Dual emission from thermally activated delayed fluorescence (TADF) emitters is often difficult to observe, especially in solution, limited by Kasha’s rule. Two TADF dendrimers containing N-doped polycyclic aromatic hydrocarbons as acceptors are designed and synthesized. Compound 2GCzBPN, having a strongly twisted geometry, exhibits TADF, while 2GCzBPPZ, possessing a less twisted geometry, shows dual emission associated with the monomer and aggregate that is TADF. The demonstration reveals that 2GCzBPPZ can serve as a temperature sensor with excellent temperature sensitivity and remarkably wide emission color response in solution. By embedding 2GCzBPPZ in paraffin we demonstrate a spatial-temperature sensor that shows a noticeable emission shift from yellow to green and ultimately to blue as the temperature increases from 20 to 200 °C. We finally demonstrate the utility of these TADF dendrimers in solution-processed organic light-emitting diodes.
Wireless, battery-free, and real-time monitoring of water permeation across thin-film encapsulation
Authors: Mariello Massimo , Rosenthal James Daniel , Cecchetti Francesco , Gao Mingxiang , Skrivervik Anja K. , Leterrier Yves , Lacour Stéphanie P.
Published: August 2024

Long-term bioelectronic implants require stable, hermetic encapsulation. Water and ion ingress are challenging to quantify, especially in miniaturized microsystems and over time. We propose a wireless and battery-free flexible platform leveraging backscatter communication and magnesium (Mg)-based microsensors. Water permeation through the encapsulation induces corrosion of the Mg resistive sensor thereby shifting the oscillation frequency of the sensing circuit. Experimental in vitro and in-tissue characterization provides information on the operation of the platform and demonstrates the robustness and accuracy of this promising method, revealing its significance for in-situ real-time monitoring of implanted bioelectronics.
Reconstruction of human dispersal during Aurignacian on pan-European scale
Authors: Shao Yaping , Wegener Christian , Klein Konstantin , Schmidt Isabell , Weniger Gerd-Christian
Published: August 2024

The Aurignacian is the first techno-complex related with certainty to Anatomically Modern Humans in Europe. Studies show that they appeared around 43-42 kyr cal BP and dispersed rapidly in Europe during the Upper Palaeolithic. However, human dispersal is a highly convoluted process which is until today not well understood. Here, we provide a reconstruction of the human dispersal during the Aurignacian on the pan-European scale using a human dispersal model, the Our Way Model, which combines archaeological with paleoclimate data and uses the human existence potential as a unifying driver of human population dynamics. Based on the reconstruction, we identify the different stages of the human dispersal and analyse how human demographic processes are influenced by climate change and topography. A chronology of the Aurignacian human groups in Europe is provided, which is verified for locations where archaeological dating records are available. Insights into highly debated hypotheses, such as human dispersal routes, are provided.
Structural basis of frizzled 7 activation and allosteric regulation
Authors: Bous Julien , Kinsolving Julia , Grätz Lukas , Scharf Magdalena M. , Voss Jan Hendrik , Selcuk Berkay , Adebali Ogün , Schulte Gunnar
Published: August 2024

Frizzleds (ten paralogs: FZD1-10) belong to the class F of G protein-coupled receptors (GPCRs), which remains poorly understood despite its crucial role in multiple key biological functions including embryonic development, stem cell regulation, and homeostasis in the adult. FZD7, one of the most studied members of the family, is more specifically involved in the migration of mesendoderm cells during the development and renewal of intestinal stem cells in adults. Moreover, FZD7 has been highlighted for its involvement in tumor development predominantly in the gastrointestinal tract. This study reports the structure of inactive FZD7, without any stabilizing mutations, determined by cryo-electron microscopy (cryo-EM) at 1.9 Å resolution. We characterize a fluctuating water pocket in the core of the receptor important for FZD7 dynamics. Molecular dynamics simulations are used to investigate the temporal distribution of those water molecules and their importance for potential conformational changes in FZD7. Moreover, we identify lipids interacting with the receptor core and a conserved cholesterol-binding site, which displays a key role in FZD7 association with a transducer protein, Disheveled (DVL), and initiation of downstream signaling and signalosome formation.
Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased affinity to Fcγ receptors during acute SHIVAD8-EO infection
Authors: Dias Joana , Fabozzi Giulia , Fourati Slim , Chen Xuejun , Liu Cuiping , Ambrozak David R. , Ransier Amy , Laboune Farida , Hu Jianfei , Shi Wei , March Kylie , Maximova Anna A. , Schmidt Stephen D. , Samsel Jakob , Talana Chloe A. , Ernste Keenan , Ko Sung Hee , Lucas Margaret E. , Radecki Pierce E. , Boswell Kristin L. , Nishimura Yoshiaki , Todd John-Paul , Martin Malcolm A. , Petrovas Constantinos , Boritz Eli A. , Doria-Rose Nicole A. , Douek Daniel C. , Sékaly Rafick-Pierre , Lifson Jeffrey D. , Asokan Mangaiarkarasi , Gama Lucio , Mascola John R. , Pegu Amarendra , Koup Richard A.
Published: August 2024

Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab and Fc domains, respectively. So far, bNAbs with enhanced Fc effector functions in vitro have only been tested in NHPs during chronic simian-HIV (SHIV) infection. Here, we investigate the effects of administering in acute SHIVAD8-EO infection either wild-type (WT) bNAbs or bNAbs carrying the S239D/I332E/A330L (DEL) mutation, which increases binding to FcγRs. Emergence of virus in plasma and lymph nodes (LNs) was delayed by bNAb treatment and occurred earlier in monkeys given DEL bNAbs than in those given WT bNAbs, consistent with faster clearance of DEL bNAbs from plasma. DEL bNAb-treated monkeys had higher levels of circulating virus-specific IFNγ single-producing CD8+ CD69+ T cells than the other groups. In LNs, WT bNAbs were evenly distributed between follicular and extrafollicular areas, but DEL bNAbs predominated in the latter. At week 8 post-challenge, LN monocytes and NK cells from DEL bNAb-treated monkeys upregulated proinflammatory signaling pathways and LN T cells downregulated TNF signaling via NF-κB. Overall, bNAbs with increased affinity to FcγRs shape innate and adaptive cellular immunity, which may be important to consider in future strategies of passive bNAb therapy.
Scalable interpolation of satellite altimetry data with probabilistic machine learning
Authors: Gregory William , MacEachern Ronald , Takao So , Lawrence Isobel R. , Nab Carmen , Deisenroth Marc Peter , Tsamados Michel
Published: August 2024

We present GPSat; an open-source Python programming library for performing efficient interpolation of non-stationary satellite altimetry data, using scalable Gaussian process techniques. We use GPSat to generate complete maps of daily 50 km-gridded Arctic sea ice radar freeboard, and find that, relative to a previous interpolation scheme, GPSat offers a 504 × computational speedup, with less than 4 mm difference on the derived freeboards on average. We then demonstrate the scalability of GPSat through freeboard interpolation at 5 km resolution, and Sea-Level Anomalies (SLA) at the resolution of the altimeter footprint. Interpolated 5 km radar freeboards show strong agreement with airborne data (linear correlation of 0.66). Footprint-level SLA interpolation also shows improvements in predictive skill over linear regression. In this work, we suggest that GPSat could overcome the computational bottlenecks faced in many altimetry-based interpolation routines, and hence advance critical understanding of ocean and sea ice variability over short spatio-temporal scales.
Risky sexual behaviors and associated factors among adolescent in Gedeo Zone, South Ethiopia: a community based cross-sectional study
Authors: Wondimagegne Yohannes Addisu , Anbese Adane Tesfaye
Published: August 2024

Adolescents represent 16% of the global population and they are identified as a critical demographic group for promoting sexual health. Adolescents are susceptible to engaging in risky sexual behaviors (RSB) such as early sexual initiation, having multiple sexual partners, substance use during sexual encounters and practicing unsafe sex. Adolescents represent 16% of the global population and they are identified as a critical demographic group for promoting sexual health. Adolescents are susceptible to engaging in risky sexual behaviors (RSB) such as early sexual initiation, having multiple sexual partners, substance use during sexual encounters and practicing unsafe sex. To assess risky Sexual behaviors and associated factors among adolescent in Gedeo Zone, Southern Ethiopia: A community based cross-sectional study. A community based cross-sectional study was conducted in Gedeo Zone among adolescents. A total of 2780 (99.3%) adolescents were participated in the study and gave the response rate of 99.3%. A pre-tested structured questionnaire was used to gather the data and analyzed by using SPSS version 23. During analysis initially bivariable logistic regression model was used then, those variables with a level of significant at a P-value ≤ 0.25 were considered as candidate for multivariable logistic regression model. A level of significant at a P-value ≤ 0.05 was considered as statistically significant in this study. Out of 428 sexually active adolescent 334 (78%) exposed to risky sexual practice. More than half 54.3% of adolescent was protestant in religion followed by Orthodox 34.2% and Muslim 11.5%. In terms of ethnicity, Gedeo 67.4% was the dominant ethnic group in the study area. Mean age at sexual initiation was 15 ± 1.8.Residence AOR 1.14 (1.36–5.25), Sex AOR 2.77 (1.31–5.86), Age AOR 2.01 (1.41–6.39), School attending AOR 1.93 (1.27–5.75), Watching Pornographies AOR 2.51 (1.36–4.62) and Parental monitoring AOR 2.10 (1.07–4.10) were independent predictor of risky sexual practice in this study. The prevalence of risky sexual behavior was found to be alarming among adolescents aged 14–19 years, mostly rural and female adolescents and those adolescent start sexual practice earlier exposed to risky sexual practice than their counter parts. Sexual urge, watching pornography and not attending school were the major factor for risky sexual behaviors of adolescent. Parental over all control can protect risky sexual behaviors among adolescent.