bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing primordial black hole scenarios with terrestrial gravitational wave detectors
Authors: Domènech Guillem , Sasaki Misao
Published: June 2024

It is possible that primordial black holes (PBHs) constitute (or constituted) a significant fraction of the energy budget of our Universe. Terrestrial gravitational wave detectors offer the opportunity to test the existence of PBHs in two different mass ranges, from102g−1016gto10−6M⊙−100M⊙. The first mass window is open via induced gravitational waves, and the second one is by gravitational waves from binary mergers. In this review, we outline and explain the different gravitational wave signatures of PBHs that may be probed by terrestrial gravitational wave detectors, such as the current LIGO/Virgo/KAGRA and future ones like Einstein Telescope and Cosmic Explorer. We mainly focus on the associated Gravitational Wave background signals and provide rough estimates for their typical frequency and amplitude. We also discuss complementary probes for these PBH mass ranges.
Holographic thermal mapping in volumes using acoustic lenses
Authors: Cengiz Ceren , Shahab Shima
Published: June 2024

Acoustic holographic lenses (AHLs) show great potential as a straightforward, inexpensive, and reliable method of sound manipulation. These lenses store the phase and amplitude profile of the desired wavefront when illuminated by a single acoustic source to reconstruct ultrasound pressure fields, induce localized heating, and achieve temporal and spatial thermal effects in acousto-thermal materials like polymers. The ultrasonic energy is transmitted and focused by AHL from a transducer into a particular focal volume. It is then converted to heat by internal friction in the polymer chains, causing the temperature of the polymer to rise at the focus locations while having little to no effect elsewhere. This one-of-a-kind capability is made possible by the development of AHLs to make use of the translation of attenuated pressure fields into programmable heat patterns. However, the impact of acousto-thermal dynamics on the generation of AHLs is largely unexplored. We use a machine learning-assisted single inverse problem approach for rapid and efficient AHLs’ design to generate thermal patterns. The process involves the conversion of thermal information into a holographic representation through the utilization of two latent functions: pressure phase and amplitude. Experimental verification is performed for pressure and thermal measurements. The volumetric acousto-thermal analyses of experimental samples are performed to offer a knowledge of the obtained pattern dynamics, as well as the applicability of holographic thermal mapping for precise volumetric temperature control. Finally, the proposed framework aims to provide a solid foundation for volumetric analysis of acousto-thermal patterns within thick samples and for assessing thermal changes with outer surface measurements.
Robust superconductivity and the suppression of charge-density wave in the quasi-skutterudites

Ca

3

(

Ir

1
−
x

Rh

x

)

4

Sn

13

single crystals at ambient pressure
Authors: Krenkel Elizabeth H , Tanatar Makariy A , Ghimire Sunil , Joshi Kamal R , Chen Shuzhang , Petrovic Cedomir , Prozorov Ruslan
Published: June 2024

Single crystals of the quasi-skutterudite compounds Ca3(Ir1-xRhx)4Sn13 (3–4–13) were synthesized by flux growth and characterized by x-ray diffraction, energy dispersive x-ray spectroscopy, magnetization, resistivity, and radio frequency magnetic susceptibility techniques. The coexistence and competition between the charge density wave (CDW) and superconductivity was studied by varying the Rh/Ir ratio. The superconducting transition temperature,

T

c

, varies from 7 K in pure Ir (x = 0) to 8.3 K in pure Rh (x = 1). Temperature-dependent electrical resistivity reveals monotonic suppression of the CDW transition temperature, T
CDW(x). The CDW starts in pure Ir, x = 0, at T
CDW ≈ 40 K and extrapolates roughly linearly to zero at

x
c

≈

0.53–0.58 under the superconducting dome. Magnetization and transport measurements show a significant influence of CDW on superconducting and normal states. Meissner expulsion is substantially reduced in the CDW region, indicating competition between the CDW and superconductivity. The low-temperature resistivity is higher in the CDW part of the phase diagram, consistent with the reduced density of states due to CDW gapping. Its temperature dependence just above

T

c

shows signs of non-Fermi liquid behavior in a cone-like composition pattern. We conclude that the Ca3(Ir1-xRhx)4Sn13 alloy is a good candidate for a composition-driven quantum critical point at ambient pressure.
Localization for surface microseismic monitoring based on arrival time correction and VFOM
Authors: Wang Chunlu , Xu Zeyan , He Renjie , Zhang Linhang , Wang Jiang , Zhou Xiaohua , Chen Zubin
Published: June 2024

Unconventional resources have emerged as the primary source to meet the escalating demand for energy consumption, with hydraulic fracturing standing out as an effective means of boosting production. The utilization of microseismic monitoring is crucial for acquiring real-time or semi-real-time extension information of the fracture network to guide the fracturing process. The precise positioning of microseismic events is a fundamental aspect of microseismic monitoring. Traditional methods relying on (relative) arrival time significantly impact positioning accuracy due to picking errors. While waveform-based methods offer high accuracy, they require precise velocity models and are time-consuming. To overcome challenges associated with arrival time pickup and velocity accuracy, we introduce a virtual field optimization method (VFOM) based on arrival time correction. Initially, an equivalent velocity model is established, and the arrival time difference resulting from the model transformation of the master event is calculated to correct the observed arrival time of the target event. Subsequently, we match detector pairs, establish hyperboloids based on the corrected arrival time difference, and employ the intersection point of all hyperboloids as the positioning result. After that, we use the location results of the master event to enhance the accuracy of the target event. Finally, we apply the proposed method to both synthetic test and field datasets, demonstrating a significant improvement in the positioning accuracy and stability provided by the novel method. The robustness against arrival time error renders it a suitable choice for surface monitoring applications where signal quality is compromised. Furthermore, the simplified velocity model significantly diminishes the computational requirements in the positioning process, enhancing its efficiency, and consequently holds vast potential for application in real-time monitoring.
Constraint-following control for dynamic systems with comprehensive constraints: the generalized Udwadia–Kalaba approach
Authors: Yu Rongrong , Lu Si , Zhu Weiyong , Wei Cui , Chen Ye-Hwa , Li Chenming
Published: June 2024

A novel generalized Udwadia–Kalaba (GUK) control method is proposed in this paper to effectively deal with the constraint-following problem with comprehensive constraints, be it equality constraints or inequality constraints. Fully considering the complex application scenario in practice which encompasses both clear and feasible trajectory, the equality constraints and inequality constraints are simultaneously applied to design rational and reliable controller. Specifically, a state transformation function is introduced to describe the inequality constraints. Further, the dynamic model with comprehensive constraints is established based on the GUK theory. Then, a corresponding constraint-following control is presented to render the system performance, uniform boundedness and uniform ultimate boundedness. The effectiveness of the GUK control is verfied by the stability analysis based on Lyapunov minimax apprach and experimental verification of unmanned underwater vehicle (UUV). The desired control performances of UUV, constraint-following and collision avoidance, can be achieved. As an illustrative application, the UUV is designed to navigate through narrow sea trenches. Meanwhile, through comparative analysis with the linear quadratic regulator method and UK method, the superiority of this approach is demonstrated.
Developing technologies to assess vascular ageing: a roadmap from VascAgeNet
Authors: Zanelli Serena , Agnoletti Davide , Alastruey Jordi , Allen John , Bianchini Elisabetta , Bikia Vasiliki , Boutouyrie Pierre , Bruno Rosa Maria , Climie Rachel , Djeldjli Djammaleddine , Gkaliagkousi Eugenia , Giudici Alessandro , Gopcevic Kristina , Grillo Andrea , Guala Andrea , Hametner Bernhard , Joseph Jayaraj , Karimpour Parmis , Kodithuwakku Vimarsha , Kyriacou Panicos A , Lazaridis Antonios , Lønnebakken Mai Tone , Martina Maria Raffaella , Mayer Christopher Clemens , Nabeel P M , Navickas Petras , Nemcsik János , Orter Stefan , Park Chloe , Pereira Telmo , Pucci Giacomo , Rey Ana Belen Amado , Salvi Paolo , Seabra Ana Carolina Gonçalves , Seeland Ute , van Sloten Thomas , Spronck Bart , Stansby Gerard , Steens Indra , Stieglitz Thomas , Tan Isabella , Veerasingham Dave , Wassertheurer Siegfried , Weber Thomas , Westerhof Berend E , Charlton Peter H
Published: June 2024

Vascular ageing (vascular ageing) is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.
Pendulum type magnetically coupled rotary piezoelectric energy harvester
Authors: Liu Xuejin , Yan Yongfeng , Zhong Feng , Yang Jingwei , Zhang Limin , He Lipeng
Published: June 2024

This research proposes a rotary motion-based non-contact pendulum piezoelectric energy harvester (P-PEH). The working region of the piezoelectric vibrator can be maintained in a magnetically coupled system at all times by means of a motion conversion mechanism. The combination of the motion conversion mechanism and the magnetic coupling system not only reduces the loss of the piezoelectric material, but also improves the output performance of the piezoelectric vibrator. The paper investigates the effects of the excitation distance L, the radius of the base circle R, and the number of excitation magnets N on the output performance of the P-PEH. When the input speed of 600 rpm, L = 10 mm, R = 21 mm, and N = 1, the peak-to-peak voltage (Vpp
) is 58.75 V. At this parameter, the output power of the device with an external 20 kΩ load is 0.0187 W. The viability of P-PEH was finally demonstrated through several application testing. P-PEH can easily light up 63 LEDs while its output energy can keep the temperature and humidity sensor in use. In summary, P-PEH can effectively collect external rotational energy for power storage and supply, and supply electricity to wireless sensor networks and microelectronic devices with further studies.
Humidity effect on electromechanical breakdown of dielectric elastomers subject to a ramp voltage
Authors: Zuo Yuchen , Huang Zihuan , Zhang Junshi , Liu Lei , Zhu Jihong , Zhang Weihong
Published: June 2024

As is known, the external excitations, material parameters, and ambient environment may affect the electromechanical properties of dielectric elastomers (DEs), which directly induce the occurrence of electrical breakdown. In this paper, we experimentally and theoretically studied the effects of voltage ramp rate, ambient humidity, electrode material, and pre-stretch on electromechanical deformation and electrical breakdown of DEs. By coupling the above four factors, the nonlinear constitutive model and electrical breakdown model of the viscoelastic DE are developed, which are shown to be consistent with the experimental observations. Firstly, when the ramp voltages with different rate are loaded to the same value, a larger voltage ramp rate leads to a smaller stretch and a higher electrical breakdown field strength of the elastomer. Besides, as the humidity increases, the electromechanical deformation increases and the electrical breakdown field decreases. In addition, it is found that different electrode materials show diverse sensitivity to the electromechanical deformation and breakdown field. Finally, with the increase of the pre-stretch from 2 to 4, the deformation and breakdown field both show an upward trend.
Design optimization of surface acoustic wave devices and investigation of fabricated devices under temperature, humidity and steam environments
Authors: Anbalagan Suganya , Lakshminarayanan Sujatha , Girija K G
Published: June 2024

Surface Acoustic Wave (SAW) technique is one of the most promising Micro Electro Mechanical Systems (MEMS) based detection methods for a variety of applications. SAW sensor is based on the modulation of Rayleigh waves that travel near the surface of a piezoelectric substrate. Advent of MEMS technology has led to the development of SAW sensors which are widely used in chemical sensing, medical, industrial, telecommunication and biological applications. The main focus of this paper is to devise and characterize a generic SAW structure and study the acoustic properties at various environmental conditions before depositing the sensing layer/analyte for any particular application. In this work, a SAW device was designed using COMSOL Multiphysics for a resonant frequency of 100 MHz with 40 μm wavelength on Lithium Niobate (LiNbO3) piezoelectric substrate. The optimized device structure was fabricated using thin film deposition and UV photolithography. The resonant frequency of the fabricated device (97.63 MHz) matched closely with the simulation results (100 MHz) and theoretical results (100 MHz). The device was subjected to various environmental conditions to study the influence on the resonant frequency. The SAW structure showed a resonant frequency shift of 90 KHz in steam environment, ∼ 1 MHz when heated to 150 °C and ∼ 120 KHz when exposed to 80% RH. The device exhibited a linear shift in resonant frequency under all tested environmental conditions with a consistent baseline and good repeatability.
Progress of research on the surface functionalization of tantalum and porous tantalum in bone tissue engineering
Authors: Li Xudong , Zhu Liwei , Che Zhenjia , Liu Tengyue , Yang Chengzhe , Huang Lanfeng
Published: June 2024

Tantalum and porous tantalum are ideal materials for making orthopedic implants due to their stable chemical properties and excellent biocompatibility. However, their utilization is still affected by loosening, infection, and peripheral inflammatory reactions, which sometimes ultimately lead to implant removal. An ideal bone implant should have exceptional biological activity, which can improve the surrounding biological microenvironment to enhance bone repair. Recent advances in surface functionalization have produced various strategies for developing compatibility between either of the two materials and their respective microenvironments. This review provides a systematic overview of state-of-the-art strategies for conferring biological functions to tantalum and porous tantalum implants. Furthermore, the review describes methods for preparing active surfaces and different bioactive substances that are used, summarizing their functions. Finally, this review discusses current challenges in the development of optimal bone implant materials.
Analytical description of the ionic relaxation in the presence of surface adsorption
Authors: Barbero Giovanni , Aliyev Yagub , Scarfone Antonio M
Published: June 2024

The temporal evolution of the surface electric field in a cell in the presence of ionic adsorption is investigated. The analysis is performed in the framework of the Poisson–Nernst–Planck model, based on the conservation of particles and the equation of Poisson for the actual electric potential across the cell, assuming that only the ions of a given sign are mobile. The adsorption is described using a kinetic equation of Langmuir’s type. The simple case of small adsorption is considered, in which the saturation effect can be neglected, and the fundamental equations of the model can be linearized. In this framework, the effective relaxation time describing the dynamics of the system is evaluated, as well as the profiles of the ions and the electric field. The case in which the sample is a half-space is first considered. A more realistic situation where the sample is a slab of thicknessd, limited by two identical or different electrodes, is analyzed too. The difference in electric potential due to the adsorption phenomenon between the electrodes is determined. Our analysis shows that its time dependence, when the electrodes have different adsorption properties, is not monotonic.
Identifying gastric cancer by optical coherence tomography based on an optimized depth-resolved attenuation estimation
Authors: Zhao Chao , Shu Yukang , Cui Lin , He Xiang , Mao Weizheng , Shi Xiaofeng , Zhao Hang , Ma Jun
Published: June 2024

Optical coherence tomography (OCT) is a reliable technique for cancer detection, with the potential to improve accuracy in identifying cancerous tissue through effective use of OCT image data. We proposed an optimized depth resolution estimation based optical attenuation coefficient (OAC) mapping method to reduce the error effect caused by discretization without considering whether the light is completely attenuated or not. The attenuation coefficient maps of gastric tissue were reconstructed using this method. Features were extracted from these maps using gray-level co-occurrence matrix and gray histogram, and a support vector machine was employed as a classifier for identifying gastric cancer tissues. The recognition accuracy achieved was 98.60%, which was higher than the 94.30% accuracy in the control group without OACs. This approach enhances the utilization of OCT image information and improves its practical application ability by increasing the recognition accuracy.
Effect of tin doping and tin-bromine co-doping on electronic and optical properties of BiOCl crystal: density functional theory
Authors: Wakjira Tadesse Lemma , Tadele Kumneger , Gemta Abebe Belay , Kassahun Gashaw Beyene
Published: June 2024

Bismuth oxychloride (BiOCl) is a layered compound known for its exceptional physical, chemical, and optical characteristics, along with notable photocatalytic performance under visible light irradiation. This investigation employed density functional theory (DFT) to analyze the electronic band structure, projected density of states (PDOS), joint density of states (JDOS), and dielectric functions of both pristine BiOCl and various doped crystalline structures utilizing a projected augmented wave basis set. The crystallographic symmetry of doped and co-doped configurations exhibited congruency with the pristine crystals. Electronic band structures were evaluated for pristine, doped, and co-doped crystalline forms. In the case of the co-doped SnxBi1−xOBrxCl1−x crystal (x = 0.0625, 0.125, and 0.25), energy band gaps of 1.40 eV, 1.42 eV, and 1.5 eV were determined, respectively, signifying a reduction in the energy band gap compared to the single doped and undoped BiOCl crystal. Analysis of the PDOS revealed that the valence band (VB) of the SnxBi1−xOBrxCl1−x crystal was characterized by Cl (p), Br (p), O (p), and Sn (s, p) states, while the conduction band (CB) primarily consisted of Bi (p) states. JDOS calculations indicated a shift in peak energy towards lower values, indicating that dopants promoted electron transitions from Cl, Sn, O, and Br p states to the Bi p state. Moreover, investigation of the dielectric function for both pure and doped BiOCl demonstrated that tin-bromine co-doping induced modifications in the static dielectric constant and dielectric permittivity of the unmodified BiOCl crystal. Ultimately, the incorporation of tin and bromine through co-doping exerted a substantial influence on the electronic and optical properties of the doped crystalline materials. Based on our computational assessments, the SnxBi1−xOBrxCl1−x configuration with x = 0.25 showcased superior visible light absorption efficiency compared to other doped variations and pristine BiOCl.
Amphistomy: stomata patterning inferred from 13C content and leaf-side-specific deposition of epicuticular wax
Authors: Askanbayeva Balzhan , Janová Jitka , Kubásek Jiří , Zeisler-Diehl Viktoria V , Schreiber Lukas , Muir Christopher D , Šantrůček Jiří
Published: June 2024

Background and Aims

The benefits and costs of amphistomy (AS) vs. hypostomy (HS) are not fully understood. Here, we quantify benefits of access of CO2 through stomata on the upper (adaxial) leaf surface, using 13C abundance in the adaxial and abaxial epicuticular wax. Additionally, a relationship between the distribution of stomata and epicuticular wax on the opposite leaf sides is studied.

Methods

We suggest that the 13C content of long-chain aliphatic compounds of cuticular wax records the leaf internal CO2 concentration in chloroplasts adjacent to the adaxial and abaxial epidermes. This unique property stems from: (1) wax synthesis being located exclusively in epidermal cells; and (2) ongoing wax renewal over the whole leaf lifespan. Compound-specific and bulk wax 13C abundance (δ) was related to amphistomy level (ASL; as a fraction of adaxial in all stomata) of four AS and five HS species grown under various levels of irradiance. The isotopic polarity of epicuticular wax, i.e. the difference in abaxial and adaxial δ (δab − δad), was used to calculate the leaf dorsiventral CO2 gradient. Leaf-side-specific epicuticular wax deposition (amphiwaxy level) was estimated and related to ASL.

Key Results

In HS species, the CO2 concentration in the adaxial epidermis was lower than in the abaxial one, independently of light conditions. In AS leaves grown in high-light and low-light conditions, the isotopic polarity and CO2 gradient varied in parallel with ASL. The AS leaves grown in high-light conditions increased ASL compared with low light, and δab − δad approached near-zero values. Changes in ASL occurred concomitantly with changes in amphiwaxy level.

Conclusions

Leaf wax isotopic polarity is a newly identified leaf trait, distinguishing between hypo- and amphistomatous species and indicating that increased ASL in sun-exposed AS leaves reduces the CO2 gradient across the leaf mesophyll. Stomata and epicuticular wax deposition follow similar leaf-side patterning.
Temporal turnover of Ceratobasidiaceae orchid mycorrhizal fungal communities with ontogenetic and phenological development in Prasophyllum (Orchidaceae)
Authors: Freestone Marc , Reiter Noushka , Swarts Nigel D , Linde Celeste C
Published: June 2024

Background and Aims

Plant–fungus symbioses may experience temporal turnover during the ontogenetic or phenological development of the host, which can influence the ecological requirements of the host plant. In this study, we investigate temporal turnover of Ceratobasidiaceae orchid mycorrhizal fungal (OMF) communities in Prasophyllum (Orchidaceae), asking whether OMF communities are subject to temporal change attributable to orchid phenology or ontogeny.

Methods

Roots of adult Prasophyllum frenchii, Prasophyllum lindleyanum and Prasophyllum sp. aff. validum from Australia were sampled between autumn and spring. Seed was sown in situ as ‘baits’ to explore the mycorrhizal associations of germinating protocorms, which were compared with OMF in roots of co-occurring adult plants. Culture-dependent and -independent sequencing methods were used to amplify the internal transcribed spacer and mitochondrial large subunit loci, with sequences assigned to operational taxonomic units (OTUs) in phylogenetic analyses. Germination trials were used to determine whether fungal OTUs were mycorrhizal.

Key Results

A persistent core of OMF was associated with Prasophyllum, with Ceratobasidiaceae OMF dominant in all three species. Phenological turnover occurred in P. lindleyanum and P. sp. aff. validum, but not in P. frenchii, which displayed specificity to a single OTU. Ontogenetic turnover occurred in all species. However, phenological and ontogenetic turnover was typically driven by the presence or absence of infrequently detected OTUs in populations that otherwise displayed specificity to one or two dominant OTUs. Ex situ germination trials showed that 13 of 14 tested OTUs supported seed germination in their host orchid, including eight OTUs that were not found in protocorms in situ.

Conclusions

An understanding of OMF turnover can have practical importance for the conservation of threatened orchids and their mycorrhizal partners. However, frameworks for classifying OMF turnover should focus on OTUs important to the life cycle of the host plant, which we suggest are likely to be those that are frequently detected or functionally significant.
Themis: advancing precision oncology through comprehensive molecular subtyping and optimization
Authors: Xi Yue , Zheng Kun , Deng Fulan , Liu Yujun , Sun Hourong , Zheng Yingxia , Tong Henry H Y , Ji Yuan , Zhang Yingchun , Chen Wantao , Zhang Yiming , Zou Xin , Hao Jie
Published: June 2024

Recent advances in tumor molecular subtyping have revolutionized precision oncology, offering novel avenues for patient-specific treatment strategies. However, a comprehensive and independent comparison of these subtyping methodologies remains unexplored. This study introduces ‘Themis’ (Tumor HEterogeneity analysis on Molecular subtypIng System), an evaluation platform that encapsulates a few representative tumor molecular subtyping methods, including Stemness, Anoikis, Metabolism, and pathway-based classifications, utilizing 38 test datasets curated from The Cancer Genome Atlas (TCGA) and significant studies. Our self-designed quantitative analysis uncovers the relative strengths, limitations, and applicability of each method in different clinical contexts. Crucially, Themis serves as a vital tool in identifying the most appropriate subtyping methods for specific clinical scenarios. It also guides fine-tuning existing subtyping methods to achieve more accurate phenotype-associated results. To demonstrate the practical utility, we apply Themis to a breast cancer dataset, showcasing its efficacy in selecting the most suitable subtyping methods for personalized medicine in various clinical scenarios. This study bridges a crucial gap in cancer research and lays a foundation for future advancements in individualized cancer therapy and patient management.
PROMER technology: A new real-time PCR tool enabling multiplex detection of point mutation with high specificity and sensitivity
Authors: Nam Hwanhee , Lee Esder , Yang Hichang , Lee Kyeyoon , Kwak Taeho , Kim Dain , Kim Hyemin , Yang Mihwa , Yang Younjoo , Son Seungwan , Nam Young-Hyean , Minn Il
Published: June 2024

Real-time polymerase chain reaction (real-time PCR) is a powerful tool for the precise quantification of nucleic acids in various applications. In cancer management, the monitoring of circulating tumor DNA (ctDNA) from liquid biopsies can provide valuable information for precision care, including treatment selection and monitoring, prognosis, and early detection. However, the rare and heterogeneous nature of ctDNA has made its precise detection and quantification challenging, particularly for ctDNA containing hotspot mutations. We have developed a new real-time PCR tool, PROMER technology, which enables the precise and sensitive detection of ctDNA containing cancer-driven single-point mutations. The PROMER functions as both a PRObe and priMER, providing enhanced detection specificity. We validated PROMER technology using synthetic templates with known KRAS point mutations and demonstrated its sensitivity and linearity of quantification. Using genomic DNA from human cancer cells with mutant and wild-type KRAS, we confirmed that PROMER PCR can detect mutant DNA. Furthermore, we demonstrated the ability of PROMER technology to efficiently detect mutation-carrying ctDNA from the plasma of mice with human cancers. Our results suggest that PROMER technology represents a promising new tool for the precise detection and quantification of DNA containing point mutations in the presence of a large excess of wild-type counterpart.
Strategies for overcoming tumour resistance to immunotherapy: harnessing the power of radiation therapy
Authors: Passelli Katiuska , Repáraz David , Kinj Remy , Herrera Fernanda G
Published: June 2024

Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment; yet their efficacy remains variable across patients. This review delves into the intricate interplay of tumour characteristics contributing to resistance against ICI therapy and suggests that combining with radiotherapy holds promise. Radiation, known for its ability to trigger immunogenic cell death and foster an in situ vaccination effect, may counteract these resistance mechanisms, enhancing ICI response and patient outcomes. However, particularly when delivered at high-dose, it may trigger immunosuppressive mechanism and consequent side-effects. Notably, low-dose radiotherapy (LDRT), with its capacity for tumour reprogramming and reduced side effects, offers the potential for widespread application. Preclinical and clinical studies have shown encouraging results in this regard.
Can we screen opportunistically for low bone mineral density using CT scans of the shoulder and artificial intelligence?
Authors: Sebro Ronnie , De la Garza-Ramos Cynthia
Published: June 2024

Objective

To evaluate whether the CT attenuation of bones seen on shoulder CT scans could be used to predict low bone mineral density (BMD) (osteopenia/osteoporosis), and to compare the performance of two machine learning models to predict low BMD.

Methods

In this study, we evaluated 194 patients aged 50 years or greater (69.2 ± 9.1 years; 170 females) who underwent unenhanced shoulder CT scans and dual-energy X-ray absorptiometry within 1 year of each other between January 1, 2010, and December 31, 2021. The CT attenuation of the humerus, glenoid, coracoid, acromion, clavicle, first, second, and third ribs was obtained using 3D-Slicer. Support vector machines (SVMs) and k-nearest neighbours (kNN) were used to predict low BMD. DeLong test was used to compare the areas under the curve (AUCs).

Results

A CT attenuation of 195.4 Hounsfield Units of the clavicle had a sensitivity of 0.577, specificity of 0.781, and AUC of 0.701 to predict low BMD. In the test dataset, the SVM had sensitivity of 0.686, specificity of 1.00, and AUC of 0.857, while the kNN model had sensitivity of 0.966, specificity of 0.200, and AUC of 0.583. The SVM was superior to the CT attenuation of the clavicle (P = .003) but not better than the kNN model (P = .098).

Conclusion

The CT attenuation of the clavicle was best for predicting low BMD; however, a multivariable SVM was superior for predicting low BMD.

Advances in knowledge

SVM utilizing the CT attenuations at many sites was best for predicting low BMD.
National myeloma patient survey shows continuing inappropriate imaging and geographical inequalities
Authors: Quinn Sandra C M , Goh Vicky , Westerland Olwen A , Pratt Guy
Published: June 2024

Objective

To evaluate the provision of imaging at diagnosis of myeloma from the service user perspective with a specific focus on how the experiences of patients align with the National Institute for Health and Care Excellence (NICE) guidelines (NG35, 2016) on first-line imaging practice for myeloma in the United Kingdom.

Methods

A national survey was performed to evaluate access to imaging from the patient’s perspective. Patients with myeloma who received their diagnosis between 2017 and March 2022 were invited to participate. Data were collected using an online survey from 895 patients and carers between 4 and 14 March 2022.

Results

Most patients had more than one imaging test. First-line MRI was used in 69.2% of respondents. First-line skeletal survey (SS, whole body X-rays) remained common (48.7% of respondents). 18F-fluorodexyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was used least often (23.1% of respondents). SS was used more often in East England (57.9%) and Scotland (61.2%) than in South East England (36.3%).

Conclusions

Despite NICE recommendations, first-line MRI was not used in a third of patients surveyed, with geographical variation in imaging practice. Patients are still undergoing multiple imaging tests at diagnosis. Healthcare professionals should continue to emphasize the superiority of MRI compared to SS to drive for improvements in care.

Advances in knowledge

Current recommendations on first-line imaging for myeloma are not provided consistently across the United Kingdom. There is a need to drive change and support healthcare professionals to deliver guidance-based recommendations to improve experience and outcomes for patients.
Retrospective study of germline variants in patients with hereditary melanoma study criteria in a real clinical practice setting
Authors: Villa-Gonzalez Jose Maria , Carrera Revilla Sergio , Lombardero Gutiérrez Lara , Gardeazabal García Jesús
Published: June 2024

Background

Five to twelve per cent of melanoma cases show aggregation of melanomas or other related tumours within the same family or individual. Genes such as CDKN2A or BAP1, among others, have been associated with this condition.

Objectives

To describe the epidemiology and clinical characteristics of patients in whom a germline genetic study was performed due to suspected hereditary melanoma.

Methods

This was a retrospective descriptive study that included patients from Cruces University Hospital who underwent a germline genetic analysis for hereditary melanoma from 2016 to 2023, having met any of the following criteria: (i) presence of two or more melanomas in the same individual; (ii) a melanoma and a pancreatic cancer in the same individual; (iii) presence of a melanoma in an individual and one or more first- or second-degree relatives with melanoma or pancreatic cancer; (iv) first- or second-degree relative of an individual with a known deleterious variant in genes associated with melanoma predisposition; or (v) incidental discovery of deleterious variants in genes associated with predisposition to melanoma, within hereditary cancer panels carried out for reasons other than melanoma.

Results

In total, 59 families were included, comprising 69 patients (64% women). Among these, 8% of families (13% of patients) presented pathogenic/likely pathogenic (P/LP) variants: 6% of families (6% of patients), excluding criteria (iv) and (v), showed P/LP variants in CDKN2A, and 2% of families (1% of patients) presented P/LP variants in BAP1, BRCA2 and TERF2IP.

Conclusions

The frequencies of P/LP variants in CDKN2A are similar to those previously described. This study could contribute to the knowledge of the characteristics of patients who meet genetic study criteria for hereditary melanoma in a setting of real-world clinical practice.
Sex differences in aberrant functional connectivity of three core networks and subcortical networks in medication-free adolescent-onset major depressive disorder
Authors: Yang Chunyu , Zhou Zilin , Bao Weijie , Zhong Ruihan , Tang Mengyue , Wang Yidan , Gao Yingxue , Hu Xinyue , Zhang Lianqing , Qiu Lihua , Kuang Weihong , Huang Xiaoqi , Gong Qiyong
Published: June 2024

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.
Safety and Effectiveness of 3 Novel All-Oral Shortened Regimens for Rifampicin- or Multidrug-Resistant Tuberculosis in Kazakhstan
Authors: Rashitov Makhmujan , Franke Molly F , Trevisi Letizia , Bekbolatova Gulzhanat , Shalimova Julia , Eshmetov Gafurzhan , Bektasov Sagit , LaHood Allison , Arlyapova Nataliya , Osso Elna , Yedilbayev Askar , Korotych Oleksandr , Ciobanu Anisoara , Skrahina Alena , Mitnick Carole D , Seung Kwonjune J , Algozhin Yerkebulan , Rich Michael L
Published: June 2024

Background

In 2019, the World Health Organization called for operational research on all-oral shortened regimens for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We report safety and effectiveness of three 9-month all-oral regimens containing bedaquiline (Bdq), linezolid (Lzd), and levofloxacin (Lfx) and reinforced with cycloserine (Cs) and clofazimine (Cfz), delamanid (Dlm) and pyrazinamide (Z), or Dlm and Cfz.

Methods

We conducted a prospective cohort study of patients initiating treatment for pulmonary MDR/RR-TB under operational research conditions at public health facilities in Kazakhstan. Participants were screened monthly for adverse events. Participants with baseline resistance were excluded from the study and treated with a longer regimen. We analyzed clinically relevant adverse events of special interest in all participants and sputum culture conversion and end-of-treatment outcomes among individuals who were not excluded.

Results

Of 510 participants, 41% were women, the median age was 37 years (25th–75th percentile: 28–49), 18% had a body mass index <18.5 kg/m2, and 51% had cavitary disease. A total of 399 (78%) initiated Bdq-Lzd-Lfx-Cs-Cfz, 83 (16%) started Bdq-Lzd-Lfx-Dlm-Z, and 28 (5%) initiated Bdq-Lzd-Lfx-Dlm-Cfz. Fifty-eight individuals (11%) were excluded from the study, most commonly due to identification of baseline drug resistance (n = 52; 90%). Among the remaining 452 participants, treatment success frequencies were 92% (95% CI: 89–95%), 89% (95% CI: 80–94%), and 100% (95% CI: 86–100%) for regimens with Cs/Cfz, Dlm/Z, and Dlm/Cfz, respectively. Clinically relevant adverse events of special interest were uncommon.

Conclusions

All regimens demonstrated excellent safety and effectiveness, expanding the potential treatment options for patients, providers, and programs.
Glucagon-like peptide-1 increases heart rate by a direct action on the sinus node
Authors: Lubberding Anniek Frederike , Veedfald Simon , Achter Jonathan Samuel , Nissen Sarah Dalgas , Soattin Luca , Sorrentino Andrea , Vega Estefania Torres , Linz Benedikt , Eggertsen Caroline Harriet Eggert , Mulvey John , Toräng Signe , Larsen Sara Agnete , Nissen Anne , Petersen Lonnie Grove , Bilir Secil Erbil , Bentzen Bo Hjorth , Rosenkilde Mette Marie , Hartmann Bolette , Lilleør Thomas Nikolaj Bang , Qazi Saddiq , Møller Christian Holdflod , Tfelt-Hansen Jacob , Sattler Stefan Michael , Jespersen Thomas , Holst Jens Juul , Lundby Alicia
Published: June 2024

Aims

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity. Albeit cardiovascular outcomes generally improve, treatment with GLP-1 RAs is associated with increased heart rate, the mechanism of which is unclear.

Methods and results

We employed a large animal model, the female landrace pig, and used multiple in vivo and ex vivo approaches including pharmacological challenges, electrophysiology, and high-resolution mass spectrometry to explore how GLP-1 elicits an increase in heart rate. In anaesthetized pigs, neither cervical vagotomy, adrenergic blockers (alpha, beta, or combined alpha-beta blockade), ganglionic blockade (hexamethonium), nor inhibition of hyperpolarization-activated cyclic nucleotide–gated (HCN) channels (ivabradine) abolished the marked chronotropic effect of GLP-1. GLP-1 administration to isolated perfused pig hearts also increased heart rate, which was abolished by GLP-1 receptor blockade. Electrophysiological characterization of GLP-1 effects in vivo and in isolated perfused hearts localized electrical modulation to the atria and conduction system. In isolated sinus nodes, GLP-1 administration shortened the action potential cycle length of pacemaker cells and shifted the site of earliest activation. The effect was independent of HCN blockade. Collectively, these data support a direct effect of GLP-1 on GLP-1 receptors within the heart. Consistently, single nucleus RNA sequencing showed GLP-1 receptor expression in porcine pacemaker cells. Quantitative phosphoproteomics analyses of sinus node samples revealed that GLP-1 administration leads to phosphorylation changes of calcium cycling proteins of the sarcoplasmic reticulum, known to regulate heart rate.

Conclusion

GLP-1 has direct chronotropic effects on the heart mediated by GLP-1 receptors in pacemaker cells of the sinus node, inducing changes in action potential morphology and the leading pacemaker site through a calcium signalling response characterized by PKA-dependent phosphorylation of Ca2+ cycling proteins involved in pacemaking. Targeting the pacemaker calcium clock may be a strategy to lower heart rate in people treated with GLP-1 RAs.
Fuelling Organised Crime: the Mexican War on Drugs and Oil Theft
Authors: Battiston Giacomo , Daniele Gianmarco , Le Moglie Marco , Pinotti Paolo
Published: June 2024

We show that the Mexican war on drugs pushed drug cartels into large-scale oil theft. We propose a simple model in which government crackdowns on one criminal sector induce criminal organisations to invest in a new sector. When entering the new sector, challenger organisations with a residual share of the market in the traditional sector may leapfrog incumbent organisations. We bring the model to the data using detailed information on drug cartel presence, oil pipelines and illegal oil taps across Mexican municipalities. In line with the model predictions, municipalities with oil pipelines witnessed a greater increase in cartel presence than municipalities without pipelines after the crackdown on drugs, and the effect is driven by challenger criminal groups. Within the subset of municipalities with oil pipelines, we observe more illegal oil taps where the political party in favour of anti-drug trafficking policy won local elections by a small margin. Because of specialisation in different criminal sectors, municipalities with pipelines did not witness a surge in violence, but they did experience a decline in socioeconomic conditions.
Accuracy of a deep learning-based algorithm for the detection of thoracic aortic calcifications in chest computed tomography and cardiovascular surgery planning
Authors: Saffar Ruben , Sperl Jonathan I , Berger Tim , Vojtekova Jana , Kreibich Maximilian , Hagar Muhammad Taha , Weiss Jakob B , Soschynski Martin , Bamberg Fabian , Czerny Martin , Schuppert Christopher , Schlett Christopher L
Published: June 2024

OBJECTIVES

To assess the accuracy of a deep learning-based algorithm for fully automated detection of thoracic aortic calcifications in chest computed tomography (CT) with a focus on the aortic clamping zone.

METHODS

We retrospectively included 100 chest CT scans from 91 patients who were examined on second- or third-generation dual-source scanners. Subsamples comprised 47 scans with an electrocardiogram-gated aortic angiography and 53 unenhanced scans. A deep learning model performed aortic landmark detection and aorta segmentation to derive 8 vessel segments. Associated calcifications were detected and their volumes measured using a mean-based density thresholding. Algorithm parameters (calcium cluster size threshold, aortic mask dilatation) were varied to determine optimal performance for the upper ascending aorta that encompasses the aortic clamping zone. A binary visual rating served as a reference. Standard estimates of diagnostic accuracy and inter-rater agreement using Cohen’s Kappa were calculated.

RESULTS

Thoracic aortic calcifications were observed in 74% of patients with a prevalence of 27–70% by aorta segment. Using different parameter combinations, the algorithm provided binary ratings for all scans and segments. The best performing parameter combination for the presence of calcifications in the aortic clamping zone yielded a sensitivity of 93% and a specificity of 82%, with an area under the receiver operating characteristic curve of 0.874. Using these parameters, the inter-rater agreement ranged from κ 0.66 to 0.92 per segment.

CONCLUSIONS

Fully automated segmental detection of thoracic aortic calcifications in chest CT performs with high accuracy. This includes the critical preoperative assessment of the aortic clamping zone.
Causal relationship between immune cells and aortic aneurysms: a Mendelian randomization study
Authors: Xiang Bitao , Li Jia , Deng Yao , Wang Junjie
Published: June 2024

OBJECTIVES

The causal association between immune cell traits and aortic aneurysm remains unknown.

METHODS

We performed a bidirectional two-sample Mendelian randomization analysis to explore the causality between 731 immune cell characteristics and the risk of abdominal aortic aneurysm and thoracic aortic aneurysms through publicly available genetic data, respectively. To examine heterogeneity and horizontal pleiotropy, Cochran’s Q test and MR-Egger intercept were utilized. Additionally, multivariable Mendelian randomization analysis and meta-analysis were performed in further analysis.

RESULTS

We found that 20 immune phenotypes had a suggestive causality on abdominal aortic aneurysm, and 15 immune phenotypes had a suggestive causal effect on thoracic aortic aneurysm. After further false discovery rate adjustment (q value <0.1), CD20 on IgD+ CD38– B cell (q = 0.053) and CD127 on CD28+ CD4+ T cell (q = 0.096) were associated with an increased risk of abdominal aortic aneurysm, respectively, indicating a significant causality between them. After adjusting for smoking, there is still statistical significance between CD127 on CD28+ CD4+ T cell and abdominal aortic aneurysm. However, after adjusting for lipids, no statistical significance can be observed between CD127 on CD28+ CD4+ T cells and abdominal aortic aneurysm. Furthermore, there is still statistical significance between CD20 on IgD+ CD38– B cells and abdominal aortic aneurysm after adjusting for lipids and smoking, which was further identified by meta-analysis.

CONCLUSIONS

We found a causal association between immune cell traits and aortic aneurysm by genetic methods, thus providing new avenues for future mechanism studies.