bluuebunny/crossref_metadata_2025 huggingface dataset:
Production of
,
, and
mesons in strong interactions*
Authors: Xu 徐 Sheng-Nan 胜男 , Xu 许 Xiao-Ming 晓明
Published: November 2024

Using the inelastic scattering of charmed strange mesons by open-charm mesons in hadronic matter produced in Pb-Pb collisions at the Large Hadron Collider, we study the production of

,

, and

mesons. Master rate equations are established for inelastic scattering. The scattering is caused by quark interchange in association with color interactions between all constituent pairs in different mesons. We consider fifty-one reactions between charmed strange and open-charm mesons. Unpolarized cross sections for the reactions are obtained from a temperature-dependent interquark potential. The temperature dependence of the cross sections causes the contributions of the reactions to the production of

,

, and

to change with decreasing temperature during the evolution of hadronic matter. For central Pb-Pb collisions at

TeV, the master rate equations reveal that the number density of

is larger than that of

, whose number density is larger than that of

.
Accretion disk of a white hole*
Authors: Li 李 Lifang 丽仿 , Cao 曹 Zhoujian 周键 , Ling 凌 Yi 意 , Wu 吴 Xiaoning 小宁
Published: November 2024

A white hole is simply a region of spacetime described by general relativity. Black holes are often assumed to form through star collapses. Based on such an assumption, the white hole region does not present. Recent research on quantum gravity indicates that a black hole must convert into a white one to avoid the singularity difficulty encountered in general relativity. If such a theory is true, it is important to ask how white holes can be observed. Anything inside a white hole must be pushed outside. However, if a white hole is empty, nothing will escape from it. We can only observe the interaction behavior between the objects falling outside and the white hole. In this paper, we observe that the structure of the accretion disk around a white hole is exactly the same as the one around a black hole. The only possibility to distinguish a white hole from a black one is the light passing through the white hole. The image properties of white holes for such scenarios are investigated in this paper. Based on our analysis and current observation facts, we cannot certainly determine if M87 and Sgr A* are black or white holes.
Surface and near-surface positron annihilation spectroscopy at very low positron energy
Authors: Mathes Lucian , Suhr Maximilian , Burwitz Vassily V. , Russell Danny R. , Vohburger Sebastian , Hugenschmidt Christoph
Published: November 2024

We present a monoenergetic positron beam specifically
tailored to the needs of (near-) surface positron annihilation
spectroscopy. The Setup for LOw-energy
Positron Experiments (SLOPE) comprises a high-activity 22Na
source, a tungsten moderator, electrostatic extraction and
acceleration, magnetic beam guidance, as well as an analysis chamber
with a movable sample holder and a γ-ray detection system.
The tungsten moderator foil, biased between 0 and 30 V, in
combination with the HV-biasable sample holder, enables positron
implantation energies between 3 eV and 40 keV. At low energies
(< 20 eV), the count rate typically amounts to 4400 counts per
second, and the beam diameter is smaller than (12±3) mm. We
conduct phase space simulations of the positron beam using COMSOL
Multiphysics® to characterize the beam
properties and compare the findings with the experimentally
determined energy-dependent beam diameter. To showcase the
capabilities of SLOPE, we perform
studies of positronium (Ps) formation on boehmite and depth-resolved
coincidence Doppler-broadening
spectroscopy (CDBS) of copper. In particular, the Ps formation
at the hydrogen-terminated surface of boehmite is found to be
maximum at a positron implantation energy of 10 eV. The range of
positron energies for which we observe Ps formation agrees with the
hydrogen ionization energy.
Multibody system dynamics for bio-robotic design and simulation based on inching-locomotion caterpillar’s gait: MBD-ILAR method
Authors: Cornejo José , Sierra J Enrique , Gomez-Gil Francisco Javier , Gallego Juan A , Biancardi Carlo M , Weitzenfeld Alfredo
Published: November 2024

Inching-locomotion caterpillars (ILAR) inspire the design of ‘inch-worm’ robots with biomimicry features, that can be adapted to different environments, such as natural, man-made, or other planets. Therefore, this work defines a novel mathematical method called Multi-Body Dynamics for Inching-Locomotion Caterpillar Robots (MBD-ILAR) to standardize the gait simulation of this type of machines, including a payload over the head to carry an object. The method is composed of 3 steps: (i) setting the model, where the input data is defined by: the phases of walk-stride (PHAWS) based on the bioinspired robotic design (BIROD) method, linkage dimensions of insect’s morphology based on the geometrical kinematic analysis (GEKINS) algorithm, the joint types, the link’s mass and center of mass, and the gravity constant. Then, (ii) kinematic analysis: to solve the orientation, velocity, and acceleration; and (iii) dynamic analysis: to obtain the joint forces, attachment forces to the ground, motor’s torque, and mechanical power. The method was applied in a case study adapting the dimensions of a real specimen—Geometridae sp. (35 000 species), for that purpose, a graphical user interface (GUI) was developed in order to get the biomechanical results that guarantee the robot’s actuator selection: (a) attachment mechanisms: vacuum pumps with suction cups (SC) or electromagnets (EM), and (b) joints: electromechanical rotary servomotors. Finally, to validate the numerical approach of MBD-ILAR, we performed an influence study of model parameters: link’s length, link’s mass, and gravity on the behavior of the attachment forces to the ground, torque, and mechanical power. The future method’s application is expected to be useful to complete the phase of the computational robotic design before the physically mechatronic implementation; in addition, it could be adapted to other arthropods.
Osteogenesis promotion on MC3T3 by micro-area potential difference (MAPD) on titanium alloy
Authors: Xie Yanchun , Chen Junfan , Fu Shan , Yu Hailong , Xuan Anwu , Wei Yongcun , Lian Yi , Yang Lei , Zhang Erlin
Published: November 2024

The ability of osseointegration of implants is an important factor in ensuring the long-term stability of bone implants in their recipient sites. In this paper, Ti–M titanium alloys with different surface micro-area potential difference (MAPD) were prepared and the adhesion, proliferation, spreading, and differentiation behavior of osteoblasts (MC3T3) on the surface of Ti–M alloy were investigated in detail to reveal the effect of MAPD on cell compatibility and osteogenic differentiation. The results showed that the alloy with high MAPD facilitated bone differentiation, demonstrating that MAPD significantly enhanced the alkaline phosphatase activity and mineralization ability of osteoblasts, and upregulated the expression of osteogenic differentiation-related factors. It is suggested that it might be a strategy to promote the surface bioactivity of titanium alloy by adjusting the surface MAPD.
Personalizing β-TCP porous scaffolds to promote osteogenesis: a study of segmental femoral defects in beagle models
Authors: Cheng Kai , Peng Yuanhao , Diao Jingjing , Zhu Haotian , Lu Qiji , Zhao Naru , Wang Yingjun , Ding Huanwen
Published: November 2024

The increasing clinical occurrence of segmental bone defects is demanding constant improvements in bone transplantation to overcome issues of limited resources, immune rejection and poor structural complement. This study aimed to develop a personalized bone defect repair modality using 3D-printed tricalcium phosphate (β-TCP) grafts and to assess its osteogenic impacts in a femoral segmental defect model in beagles, as a basis for clinical studies and application. A β-TCP scaffold was designed and manufactured using computer-aided design. A 3 cm segmental bone defect model was established in 27 one-year-old male beagles, and were randomly divided into three groups. The control group utilizing only intramedullary fixation, the autograft group with an added autologous bone graft and β-TCP group using a β-TCP scaffold. The study animals were monitored for 24 weeks postoperative and assessed for vital signs, imaging, and histological indicators periodically. All of the Beagles underwent successful modeling and experimentation, and were fully ambulatory at four weeks. Postoperative x-rays showed no evidence of loosening or displacement of the intramedullary nails. Micro-CT and histological staining indicated Osteogenesis starting from the fourth week, with the most significant growth seen using autografts (P < 0.05). New bone (NB) formation is seen adhering to the surface and proximal femur after osteotomy. The β-TCP group had significantly more evidence of Osteogenesis when compared to the control group (P < 0.05), characterized by NB visible throughout the porous structure and distal residual femur. The control group showed bone formation impeded by fibrosis, showing poor bone growth mainly around the distal end after osteotomy, with poor overall repair outcomes. Conclusion. Growth factor-deficient β-TCP porous scaffolds demonstrated promising Osteoinductive properties in repairing large segment bone defects in Beagles’ femurs. It effectively promoted bone growth and is structurally advantageous for weight bearing long bones.
Evaluation of ecosystem’s response to flash drought in water-limited regions of China
Authors: Yao Tingting , Liu Suxia , Hu Shi , Mo Xingguo
Published: November 2024

Intensive and frequent flash droughts pose a threat to the stability of terrestrial ecosystems and affect land carbon sinks, particularly in vulnerable water-limited regions. Here, we evaluated variations in flash drought events in water-limited regions of China from 2001 to 2022 and quantified vegetation resistance (its ability to maintain predrought level) and resilience (its capacity to bounce back from droughts) to flash drought based on solar-induced chlorophyll fluorescence and gross primary productivity. The average frequency of flash droughts was approximately 3.5 events per decade and the duration increased significantly by 3 d during 2001–2022. We found that vegetation resistance to flash drought did not show significant temporal changes, while resilience decreased significantly. Spatially, as aridity increased, vegetation resistance gradually decreased while resilience rose. The strong negative correlation between resistance and resilience demonstrated a trade-off in individual climate regions, which varied among different vegetation types. Among eight vegetation types, evergreen needleleaf forest, evergreen broadleaf forest and mixed forest displayed high-resistance and low-resilience, while deciduous needleleaf forest exhibited both high-resistance and high-resilience. Furthermore, we revealed that aridity index, vapor pressure deficit, and temperature were the most relevant environmental variables for both vegetation resistance and resilience, but had opposite effects and different magnitudes. Our findings highlight that the vulnerability and stability of terrestrial ecosystems are decreasing and are affected by water availability.
Social resilience to changes in climate over the past 5000 years
Authors: Yang Liang Emlyn , Weinelt Mara , Unkel Ingmar , Petrie Cameron A
Published: November 2024

Increasing numbers of studies are investigating the phenomenon of social resistance, particularly instances of stability or prosperity in the face of climatic–environmental stresses over a long period. This emerging research field of climate resilience explores the capability of socio-ecological systems to cope with stresses, maintain functions, and evolve into more desirable systems within stressful climatic and environmental conditions. This synthetic review examines historical and archaeological studies on climate resilience especially concentrating on human societies in the past 5000 years. It highlights that human societies have had a degree of general resilience to climate and environmental stresses over various spatial and temporal scales, which is reflected through the evidence of population growth, agriculture development, settlement expansion and continuing social-economic development in hazard-prone conditions. Many of the cases considered here demonstrate that climate resilience manifests as a profile of resilience loop and scale relationships in different social systems. Multiple and diverse measures have been identified as being helpful in enhancing the resilience level of various social systems, e.g. improvement of infrastructure, knowledge and technology development, and the strengthening of social organization and cooperation. This review emphasizes the necessity and priority of deepening our understanding of long-term resilience dynamics, and it calls for holistic studies in the field of climate resiliology, particularly targeting to effective and efficient resilience measures as well as their transference across time and space.
Livestock–cropland re-coupling and intensive farming: strategies for enhancing greenhouse gas mitigation and eco-efficiency in wheat–maize production in North China Plain
Authors: Wang Beibei , Wang Peifang , He Hongxing , Zorn Conrad , Guo Wenzhou , Wu Jiarui , Yu Chaoqing , Huang Xiao
Published: November 2024

Using manure compost can be an effective strategy to sustain crop production, mitigate greenhouse gas (GHG) emissions, and promote soil organic carbon (SOC) sequestration. However, in the North China Plain (NCP)—a key food hub in China—the disconnect between livestock farms and croplands limits manure recycling, obscuring its potential environmental benefits and economic costs. This study employs a life cycle assessment method to quantify GHG and ammonia emissions, SOC sequestration, economic performance, and the eco-efficiency of wheat–maize production in the NCP across six livestock–cropland coupling scenarios: farmers’ practice (FP), traditional household farming (HF), modern intensive decoupled systems with low (L), medium (M), and high (H) manure returning rates, and an intensive coupled system with optimum manure returning rate (IC). The results show that increasing manure return rates in intensive systems decreases the net global warming potential (NGWP), emphasizing the importance of livestock–cropland re-coupling. Emissions embodied in the field input supply chain was identified as a major NGWP contributor, while SOC accumulation significantly contributed to net GHG mitigation. The IC scenario is both the most economically viable ($322.8 (t grain)−1) and eco-efficient (1.03 kg CO2-eq USD−1) system. With the same compost application rates, intensive farming reduced the NGWP by 26.1% compared to household farming, despite trade-offs between GHG and NH3 emissions. The FP scenario had the highest climate impact (722.8 kg CO2-eq (t grain)−1) and the lowest eco-efficiency (4.91 kg CO2-eq USD−1). These insights advance our understanding of sustainable management practices for pursuing synergistic progress in economic gains, environmental conservation, and sustainable agricultural production.
Enhanced LoRaWAN performance through advanced spread factor allocation empowered by machine learning
Authors: Rao M Rajeswara , Sundar S
Published: November 2024

In Wide Area Networks (WANs), optimal resource allocation is crucial for enhancing computational efficiency, particularly in Low Power Wide Area Networks (LPWANs). This work introduces a machine learning-based system to optimize data transfer rates while minimizing power consumption in LPWANs. The focus is on LoRa, a notable LPWAN technology for long-range communication and interference resilience. Existing LoRa networks experience performance degradation due to interference and congestion caused by the Internet of Things (IoT). To address this, advanced Spreading Factor (SF) allocation techniques are employed, using a metaheuristic optimization algorithm (Particle Swarm Optimization) and an ensemble machine learning algorithm based on gradient boosting (XGBoost), alongside Decision Tree Classifier (DTC) and Random Forest (RF). Simulation results reveal that these approaches significantly enhance Packet Delivery Ratio (PDR) and reduce transmit energy consumption across various distances, outperforming traditional SF schemes. The RF method, for instance, achieves up to 6.32% higher PDR and reduces energy consumption by up to 16.67% compared to the Lowest SF method. Additionally, these techniques improve throughput by up to 14.9% over classical methods. The study also examines the effects of gateways, network distance, and SF on PDR and energy utilization, demonstrating that the proposed methods adapt effectively to different network conditions. The findings highlight the potential of these advanced methods to enhance LoRa network performance, making them suitable for large-scale IoT deployments.
Philosophy as Descartes Found It
Authors: Copenhaver Brian
Published: November 2024

What was philosophy like before Descartes reformed it? What parts of philosophy did he reform, and what tools did he use? To answer such questions, how should philosophers do their work today? Some answers are surprising—that Descartes wrote picture books, for example. And some are challenging—that philosophers would do their work better by spending less time on philosophy as they commonly understand it. Philosophy changes for non-philosophical reasons that need philosophical attention, and oblivion impedes the contemporary study of philosophy’s past. Attending to those undervalued reasons will show how to repair the harm done by oblivion.
Implementation of a novel framework for hepatitis C diagnosis and treatment in an academic health system
Authors: Sheehan Lindsey P , Wright Maribeth P , Rhudy Christian , Osborne Thai , Platt Thom , Duckworth Deborah L
Published: November 2024

Purpose

Hepatitis C viral infection is a major public health concern and leading cause of chronic liver disease in the United States. Hepatitis C is primarily transmitted through blood exchange and is highly prevalent among people who inject drugs. Despite the availability of direct-acting antiviral (DAA) treatment, cost and barriers to access remain prohibitive for many patients.

In 2018, University of Kentucky HealthCare (UKHC) began a screening program for patients admitted to its emergency department (ED). Despite identifying hepatitis C RNA–positive patients, connection to care proved challenging due to unavailability of follow-up clinic appointments, communication barriers, and lack of insurance coverage. In 2023, UKHC implemented a pharmacist-led hepatitis C screening, assessment, and treatment initiative in the ED following American Association for the Study of Liver Diseases (AASLD) simplified treatment guidelines. Pharmacists order needed laboratory assessments and complete imaging for liver fibrosis in eligible patients. Patients diagnosed with hepatitis C who meet simplified treatment criteria are prescribed DAA therapy by a hepatitis C advanced practice provider employed by the program. The UKHC specialty pharmacy then follows up with dispensing of DAA therapy and proactive refill management for subsequent fills.

Conclusion

This holistic, interdisciplinary treatment model has allowed UKHC to increase treatment attachment rates for hepatitis C diagnoses in the ED from approximately 10% to 54%. This program has also reduced the median time to treatment of hepatitis C–infected individuals encountered in the ED from approximately 420 days to 17 days.
Mural nodules and prevalence of high-grade dysplasia in branch duct intraductal papillary mucinous neoplasm of the pancreas undergoing resection
Authors: Lorenzo Diane , Aguilera Munoz Lina , Vedie Anne-Laure , Prat Frédéric , Dokmak Safi , Sauvanet Alain , Maire Frédérique , de Mestier Louis , Copin Pauline , Burgio Marco Dioguardi , Couvelard Anne , Haumaitre Cécile , Cros Jérôme , Rebours Vinciane
Published: November 2024

Background

A mural module (MN) within a branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) could be a potential target for local treatment. The main aim was to describe the location of the highest grade of dysplasia relative to the mural module to assess the relevance of local treatment.

Methods

Observational study of patients who underwent a pancreatic resection for suspected high-risk IPMN because of a mural module within a BD-IPMN (2012–2022). All patients had preoperative imaging confirming the enhancing mural module. The mural module was considered as a theoretical appropriate target for local destruction if no cancer or high-grade dysplasia (HGD) was described elsewhere than in the mural module.

Results

Eighty-two patients (male: 44 (54%); mean age: 65 ± 9.2 years) were included. The mean size of BD-IPMN containing the mural module was 32 ± 14.8 mm. The mural module mean diameter was 10.5 ± 5.6 mm, and the main pancreatic duct (MPD) mean diameter was 5.2 ± 3.6 mm. Six patients presented invasive carcinoma (7%), 37 had HGD (45%), and 39 (48%) had exclusively low-grade dysplasia. The mural module was dysplastic in 70 cases (85%). The mural module was considered a relevant target for local ablation in 45 patients (55%), whereas 37 patients (45%) had HGD/invasive carcinoma distant from the mural module. HGD was exclusively present in the mural module in 6/82 patients (7%). Factors independently associated with ‘relevant indication for local treatment’ were female gender (P = 0.004; OR = 5.2, 95% c.i. 1.7 to 15.9) and MPD < 5 mm (P < 0.0001; OR = 8.6, 95% c.i. 2.7 to 26.8).

Conclusion

In resected pancreata, BD-IPMN mural modules are associated with HGD distant from the mural module almost half of cases. The findings question the safety of local treatment, supporting pancreatectomy as the best approach.
Lexical markers of disordered speech in primary progressive aphasia and ‘Parkinson-plus’ disorders
Authors: Henderson Shalom K , Ramanan Siddharth , Patterson Karalyn E , Garrard Peter , Patel Nikil , Peterson Katie A , Halai Ajay , Cappa Stefano F , Rowe James B , Lambon Ralph Matthew A
Published: November 2024

Connected speech samples elicited by a picture description task are widely used in the assessment of aphasias, but it is not clear what their interpretation should focus on. Although such samples are easy to collect, analyses of them tend to be time-consuming, inconsistently conducted and impractical for non-specialist settings. Here, we analysed connected speech samples from patients with the three variants of primary progressive aphasia (semantic, svPPA N = 9; logopenic, lvPPA N = 9; and non-fluent, nfvPPA N = 9), progressive supranuclear palsy (PSP Richardson’s syndrome N = 10), corticobasal syndrome (CBS N = 13) and age-matched healthy controls (N = 24). There were three principal aims: (i) to determine the differences in quantitative language output and psycholinguistic properties of words produced by patients and controls, (ii) to identify the neural correlates of connected speech measures and (iii) to develop a simple clinical measurement tool. Using data-driven methods, we optimized a 15-word checklist for use with the Boston Diagnostic Aphasia Examination ‘cookie theft’ and Mini Linguistic State Examination ‘beach scene’ pictures and tested the predictive validity of outputs from least absolute shrinkage and selection operator (LASSO) models using an independent clinical sample from a second site. The total language output was significantly reduced in patients with nfvPPA, PSP and CBS relative to those with svPPA and controls. The speech of patients with lvPPA and svPPA contained a disproportionately greater number of words of both high frequency and high semantic diversity. Results from our exploratory voxel-based morphometry analyses across the whole group revealed correlations between grey matter volume in (i) bilateral frontal lobes with overall language output, (ii) the left frontal and superior temporal regions with speech complexity, (iii) bilateral frontotemporal regions with phonology and (iv) bilateral cingulate and subcortical regions with age of acquisition. With the 15-word checklists, the LASSO models showed excellent accuracy for within-sample k-fold classification (over 93%) and out-of-sample validation (over 90%) between patients and controls. Between the motor disorders (nfvPPA, PSP and CBS) and lexico-semantic groups (svPPA and lvPPA), the LASSO models showed excellent accuracy for within-sample k-fold classification (88–92%) and moderately good (59–74%) differentiation for out-of-sample validation. In conclusion, we propose that a simple 15-word checklist provides a suitable screening test to identify people with progressive aphasia, while further specialist assessment is needed to differentiate accurately some groups (e.g. svPPA versus lvPPA and PSP versus nfvPPA).
CCE under nonrandom heterogeneity
Authors: Kaddoura Yousef , Westerlund Joakim
Published: November 2024

In panel data regression models, it is often not reasonable to expect all cross-sectional units to have identical responses to explanatory variables, or that all relevant variables have been properly accounted for. These concerns have recently motivated the use of interactive effects models with heterogeneous slopes. The workhorse of this literature is the common correlated effects approach, which assumes that both effects and slopes are randomly distributed. The current paper argues that the restrictions implied by this assumption are likely unreasonable in many applications, and that there is a need to allow for nonrandom heterogeneity.
Heart failure of very rare aetiology—haemochromatosis Type 3: a case report
Authors: Montvilaitė-Laurinavičienė Aistė , Dirsienė Rūta , Neverauskaitė-Piliponienė Gintarė , Banišauskaitė Audra , Šukys Marius , Šakalytė Gintarė , Ereminienė Eglė
Published: November 2024

Background

Haemochromatosis is a pathological condition characterized by the accumulation of iron in parenchymal organs, leading to toxic damage and dysfunction. Cardiac haemochromatosis represents one of the rare causes of severe heart failure (HF) that can be potentially prevented with targeted treatment.

Case Summary

We present the case of a 41-year-old female who was hospitalized for decompensated HF. Echocardiography revealed severe systolic dysfunction with a phenotype of dilated cardiomyopathy, accompanied by secondary moderate mitral regurgitation and severe tricuspid regurgitation (TR). To differentiate potential causes of HF, coronary angiography, cardiac magnetic resonance imaging (MRI), and endomyocardial biopsy were performed. Based on clinical findings, laboratory results, cardiac MRI, and endomyocardial biopsy data, a diagnosis of haemochromatosis was confirmed, and mutations in the TFR2 gene, responsible for haemochromatosis Type 3, were identified. The patient was treated in accordance with the latest European Society of Cardiology HF guidelines, and specific treatment for haemochromatosis, including therapeutic phlebotomy and iron chelation therapy, was initiated, resulting in a significant positive outcome.

Discussion

Investigating the aetiology of HF is essential, as even rare causes can be identified, and specific treatments are available that significantly improve prognosis and survival.
Assessment of co-resistance to antibiotics recommended for acute pyelonephritis among Escherichia coli clinical strains from community- and nursing home–acquired urinary tract infections
Authors: Leroy Anne-Gaëlle , Lemenand Olivier , Thibaut Sonia , Coeffic Thomas , Chauveau Marie , Lesprit Philippe , Caillon Jocelyne , Boutoille David , Birgand Gabriel ,   French Clinical Laboratories Nationwide Network, Vrain A , Andorin P , Besson J , Maillet F , de Gastines G , Léonard P-Y , Guery M , Plong V , Le Moing N , Kerdavid F , Reinhard A-S , Gillard S , Guesnon B , Gestin B , Banctel H , Laforest D , Pradier E , Arsene S , Holstein A , Bouvet D , Dubet B , Laudignon C , Jobert E , Gebeile R , Poyet S , Deleglise G , Lecordier N , Fougnot S , Grandsire E , Rault J-P , Defrance G , Cadenet J , Libier L , Touzalin A , Allery A , Valade H , Payro G , Boraud D , Parisi E , Alluin F , Bayette J , Aran M-F , Stevenin P , François A , Gay G , Duquesnoy O , Sainte Rose V , Dos Santos F , Desjardins A , Paolini M-C , Marchenay P , Berger-Carbonne Anne , Maugat Sylvie
Published: November 2024

Objectives

This study aimed to assess the frequency of co-resistance to antibiotics recommended in acute pyelonephritis among Escherichia coli clinical strains isolated from urinary tract infections (UTIs) acquired in community or nursing homes (NHs), and to identify situations without alternatives to fluoroquinolones (FQs).

Methods

All antimicrobial susceptibility test (AST) results of E. coli culture-positive urine samples from females living in the community or in NHs, collected through a large network of clinical laboratories in 2020 in France, were included. The percentages of strains resistant to amoxicillin alone or combined with a resistance to one to four alternatives among amoxicillin/clavulanic acid, trimethoprim/sulfamethoxazole, cefixime and FQs were calculated and compared between age categories and settings.

Results

Among 291 367 E. coli strains from community-acquired UTIs, 60.3% were susceptible to amoxicillin (<65-year-olds: 61.8% versus ≥65-year-olds: 58.8%; P < 0.001), and 99.1% to oral alternatives to FQs. Co-resistance to amoxicillin and trimethoprim/sulfamethoxazole was higher among females ≥65 years old versus <65 years old (7.1% versus 6.1%; P < 0.01), as well as co-resistance to amoxicillin, amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole (8.6% versus 10%; P < 0.001). Among 11 340 strains from NH UTIs, 51.2% were susceptible to amoxicillin, and 98% to oral alternatives to FQs. Co-resistance to amoxicillin, amoxicillin/clavulanic acid and/or cefixime was higher in isolates from females ≥65 years old living in NHs versus in the community (respectively 11.9% versus 15.3%, P < 0.001; 0.8% versus 2.8%, P < 0.01; 1.7% versus 4.4%, P < 0.01).

Conclusions

Based on AST results, prescribing oral alternatives to FQs for females may be possible in ≥99% of E. coli acute pyelonephritis cases in the community, and ≥98% in NHs.
‘It’s Me, Hi, I’m The Problem, It’s Me’: Re-recording as an alternative to statutory copyright reversion
Authors: Yuvaraj Joshua
Published: November 2024

This article examines re-recording of music as a way for artists to better capitalize on the popularity of their music. It does so in the context of Taylor Swift’s wild success re-recording her albums following a dispute over the ownership of her original master recordings. It considers how re-recording can better protect authors against unduly imbalanced contracting dynamics with record companies than the main mechanism for doing so in copyright law, statutory reversion (where the law allows creators to reclaim assigned or licensed copyright outside the bounds of contracts). The article interrogates common law reversion schemes in the context of sound recordings, with a special focus on the USA’s copyright ‘termination’ scheme (allowing creators to reclaim copyright after around 35 years). It then shows how re-recording may bypass reversion’s problems, though re-recording carries significant risks that make its future uncertain, and which authors should be aware of.
Application of Kaluza–Klein theory in modelling compact stars: exploring extra dimensions
Authors: Horváth Anna , Forgács-Dajka Emese , Barnaföldi Gergely Gábor
Published: November 2024

A theoretical framework for calculating the mass–radius curve of compact stars in the Kaluza–Klein space–time is introduced, with one additional compact spatial dimension. Static, spherically symmetric solutions are considered, with the equation of state provided by a zero temperature, interacting multidimensional Fermi gas. To model the strong force between baryons, a repulsive potential is introduced, which is linear in the particle number density. The maximal mass of compact stars is calculated for different model parameters, and with a physical parameter choice, it satisfies observational data, meaning that it is possible to model simple, realistic objects within this framework. Based on this comparison, a limiting size for the observational regime of extra dimensions in compact stars is provided, with $r_\mathrm{c} \gtrsim 0.2$ fm.
The threshold for pulsar radio emission is determined by the Goldreich–Julian charge density
Authors: Jones P B
Published: November 2024

A recent phenomenological study of radio emission from normal and millisecond pulsars by Karastergiou et al. has lead these authors to state that they are unable to exclude a common physics process as the source although the rotation periods and magnetic fields of these two classes are very different. This has bearing on the nature of that source and it is the purpose of the present Letter to explore this problem further, specifically, for the ion–proton model and for all those models that assume electron–positron pair creation above the polar cap. The ion–proton model satisfies this commonality and we briefly mention some consequences of this finding.
10001- ANGI-1 TRIAL OF MULTI-OMICS ANALYSES USING PAIRED SAMPLES FROM NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMAS DURING BEVACIZUMAB THERAPY
Authors: Tanaka Toshihide , Iwauchi Ai , Fukasawa Nei , Takei Jun , Teshigawara Akihiko , Tomoto Kyoichi , Yamamoto Yohei , Hasegawa Yuzuru , Akasaki Yasuharu , Shimoda Masayuki , Murayama Yuichi
Published: November 2024

BACKGROUND

We explored multi-omics analyses using surgical samples obtained from patients received preoperative neoadjuvant bevacizumab therapy (neoBev) for newly diagnosed glioblastoma (nGBM) and its recurrence (rGBM).

MATERIALS AND METHODS

Of all eight surgical samples from two cases treated by neoBev and two cases without preoperative Bev therapy (naiveBev) at nGBM and rGBM were analysed.

RESULTS

Compared with naiveBev, expression levels of VEGF, HIF-1 alpha, FOXM1 in neoBev were downregulated, whereas CD163 was upregulated. By comparison between long and short overall survival (OS), Foxp3/CD8 ratio and FOXM1 were decreased in long OS. The transcriptional factor induced under hypoxia was significantly elevated in naiveBev with long OS.

DISCUSSIONS AND CONCLUSIONS

Analyses by space multi-omics provided novel findings correlated with specific gene expressions and anatomical location focused on tumor microenvironment, which might be quite useful to comprehend the mechanism of effectiveness and resistance of targeted therapies including antiangiogenic or immunotherapies. But problems were listed as follows; cumbersome interpretation of huge amount of information for which might be essential of co-operation by skillful bioinformaticians, and huge amount of cost. Those problems especially for cost-effectiveness should be solved for the development of this field of clinical and basic research.
10168- GEN-11 GENETIC ANALYSIS OF PRIMARY BREAST CANCER TUMORS AND BRAIN METASTASIS TUMORS WITH RNA-SEQ
Authors: Sakakibara Ayaka , Kaneko Masayo , Shirahata Mitsuaki , Sato Tetsuya , Yasuda Masanori , Osaki Akihiko , Mishima Kazuhiko
Published: November 2024

BACKGROUND

Breast cancer is the most common malignancy in women; brain metastasis is a marked cause of mortality. Recent genomic studies have identified distinct genetic profiles in brain metastases, suggesting unique mechanisms underlying treatment resistance. This study aimed to compare gene expression in primary breast tumors and the corresponding brain metastases to identify potential biomarkers and therapeutic targets.

METHODS

Eight paired samples of primary breast tumors and brain metastases from patients who developed brain metastases after radical mastectomy were analyzed. RNA sequencing was used to comprehensively assess gene expression differences between the two tumor types.

RESULTS

RNA sequencing revealed 391 downregulated and 474 upregulated genes in brain metastases compared to primary tumors. Gene set enrichment analysis revealed that epithelial-mesenchymal transition (EMT)-associated genes (SPP, GREM1, and MMP3) were upregulated in primary breast tumors. Conversely, reactive oxygen species (ROS)-related genes (GPX4 and PRDX family members) were upregulated in brain metastases.

CONCLUSION

High expression of EMT-related genes in primary tumors indicates that these tumors prepare for metastasis by inducing EMT during radical resection, enabling tumors to invade the surrounding tissues and metastasize to distant organs. Additionally, ROS-related genes are highly expressed in metastatic brain tumors, suggesting that these genes contribute to tumor enhancement at the metastatic site. These findings could aid in development of biomarkers for predicting brain metastasis and for identifying novel therapeutic targets. In future, we aim to analyze tumor localization and functions of these gene products.
10065- ET-6 MRNA-ENCAPSULATED LIPID NANOPARTICLES FOR MALIGNANT GLIOMA
Authors: Hiu Takeshi , Matsuo Ayaka , Kamiya Mariko , Matsumoto Makoto , Yoshida Michiharu , Nakamura Hikaru , Baba Shiro , Kawakami Shigeru , Matsuo Takayuki
Published: November 2024

Nucleic acid therapeutics hold promise for cancer treatment but have yet to be effectively applied to malignant glioma due to challenges in stability and delivery. We explored the intracerebral delivery of lipid nanoparticles (LNPs) encapsulating siRNA as a drug delivery carrier. Our goal was to develop an siRNA therapy selectively targeting malignant glioma cells by combining LNPs with Fc-domain-binding peptide lipids (FcBPs), a modification system that allows antibody orientation control. Intracerebral Delivery of mRNA-Encapsulated Lipid Nanoparticles: We aimed to deliver mRNA-encapsulated LNPs to the brain using focused ultrasound (FUS) and microbubbles (MB). Following the administration of microbubbles and mRNA-encapsulated LNPs in normal mice, FUS irradiation was performed on the brain. The introduction of firefly luciferase mRNA resulted in gene expression that was 20 times higher in the FUS-irradiated brain compared to the non-irradiated side. Gene expression was observed in vascular endothelial cells throughout the brain and in parenchymal cells outside the brain blood vessels at the FUS-irradiated site. Development of siRNA Medicines: We prepared FcBP-modified siRNA-LNPs targeting integrin αvβ3, highly expressed in malignant gliomas, using siRNA-Luc2. The modifications with FcBP or anti-integrin αvβ3 antibody did not alter the physicochemical properties or polydispersity index (PDI). In vitro, anti-integrin αvβ3-FcBP-modified siRNA-LNPs inhibited the binding of integrin to U87-MG-Luc2 cells, demonstrating high binding affinity and knockdown effects via αvβ3.Discussion:Our findings suggest that the delivery of mRNA-encapsulated LNPs into the brain is feasible using FUS and MB. Additionally, we successfully developed siRNA-LNPs modified with anti-integrin αvβ3 antibody FcBP. Future work will evaluate the cell binding and antitumor effects of siRNA-VEGF encapsulated in these LNPs, aiming to develop new treatments for malignant glioma by enhancing blood-brain barrier penetration and targeting malignant glioma.
10162- TB-6 VALIDATION OF BORON NEUTRON CAPTURE THERAPY WITH EXISTING BORON COMPOUNDS IN A RAT MALIGNANT GLIOMA MODEL
Authors: Kashiwagi Hideki , Kawabata Shinji , Eza Kenichiro , Kambara Akihiro , Yoshimura Kohei , Fujikawa Yoshiki , Futamura Gen , Hiramatsu Ryo , Nonoguchi Naosuke , Furuse Motomasa , Hu Naonori , Takata Takushi , Tanaka Hiroki , Watanabe Tsubasa , Suzuki Minoru , Miyatake Shin-Ichi , Wanibuchi Masahiko
Published: November 2024

BACKGROUND

Boron neutron capture therapy (BNCT) is a biologically targeted particle therapy that utilizes the capture reaction between boron and neutrons. Theoretically, tumor cell-selective boron uptake allows for tumor-selective therapy. Recently, BNCT using an accelerator neutron source has been initiated in the area of head and neck cancers and is expected to expand its application to brain tumors. In addition to boronophenylalanine (BPA), which is used in clinical practice, clinical trials for malignant gliomas have been conducted in the past using sodium borocaptate (BSH) in combination. However, to date, surprisingly few reports have accurately evaluated the validation of BNCT with BPA and BNCT with BPA/BSH in animal models. In the present study, we performed a basic research-based validation of BPA/BSH combined BNCT that has been performed in clinical trials in the past.

METHODS

Brain tumor models of F98 rat malignant glioma brain tumors were prepared. BPA and BSH were administered intravenously 2.5 hours and 12 hours before BNCT were performed, respectively. Each F98 rat malignant glioma brain tumor model was neutron irradiated and evaluated using Kaplan-Meier survival curves.

RESULTS

No significant difference in survival was observed in the BSH alone group compared to the untreated group. A significant difference in survival was observed in the BPA alone group compared to the untreated group. The BPA/BSH combination group had the longest median survival and a significant difference in survival compared to the untreated group. A significant difference in survival was observed between the BPA/BSH combination group and the BSH alone group.

CONCLUSION

The combination of BPA and BSH improved BNCT efficacy and prolonged survival. The combination of BPA and BSH, existing boron compounds, is a pioneering method of boron neutron capture therapy using two and more boron compounds, and its use is presumed to have been highly rational.
10253- ACT-16 OUTCOMES OF MAINTENANCE THERAPY USING TUMOR TREATING FIELDS (TTF) FOR GLIOBLASTOMA AND CHARACTERISTICS FOR CONTINUATION OF TTF MAINTENANCE THERAPY
Authors: Shimizu Kazuhide , Tamura Kaoru , Tanaka Yoji , Takahashi Shota , Shiraishi Midori , Osuga Hiroko
Published: November 2024

BACKGROUND

Tumor Treating Fields (TTF) is a novel therapy that inhibits tumor cell division and has been reported to be safe and effective in real-world settings for newly diagnosed glioblastoma in Japan since its insurance coverage in December 2017. This study evaluates the outcomes and characteristics for the continuation of TTF treatment at the Department of Neurosurgery, Tokyo Medical and Dental University.

METHODS

We retrospectively analyzed adult patients with newly diagnosed supratentorial glioblastoma who completed initial surgery and chemoradiotherapy and began outpatient maintenance therapy between December 2018 and August 2024. Patients were divided into TTF treatment (T group) and non-TTF treatment (N group). The primary endpoints were overall survival (OS) and progression-free survival (PFS), with additional evaluations of patient characteristics and TTF array adherence.

RESULTS

The study included 49 patients (T group: 14, N group: 35) with a mean age of 66 years (range 25-86). All cases were pathologically diagnosed as glioblastoma (WHO 2016 and 2021). The mean duration of TTF treatment was 282 days (21-1155 days), with a median of 124 days. OS was 837 days (27.9 months) in the T group and 536 days (17.9 months) in the N group (p=0.17), while PFS was 961 days (32.0 months) in the T group and 196 days (6.5 months) in the N group (p=0.012). Long-term TTF users (>=12 months) showed a trend towards extended OS and PFS compared to shorter-term users, with a significantly lower adherence rate at 3 months in early discontinuation cases (p=0.014).

CONCLUSION

TTF is an effective maintenance therapy for glioblastoma patients, with early high adherence being crucial for its success. Comprehensive patient support, including social aspects, is essential for the continuation of TTF treatment.
10305- ACT-17 EFFECTIVENESS OF DABRAFENIB AND TRAMETINIB IN PATIENTS WITH GLIOMA WITH MUTATION OF BRAF V600E: A SINGLE CENTER ANALYSIS.
Authors: Yanagisawa Shunsuke , Oono Makoto , Kawauchi Daisuke , Omura Takaki , Aoki Takuma , Kawanishi Akiya , Narita Yoshitaka
Published: November 2024

BACKGROUND

In tumor cells, Dabrafenib (DB) acts on the mutated BRAF itself, and Trametinib (TR) acts on MEK and suppresses cell proliferation, and the combination of the two drugs is used for melanoma with BRAF mutations, non-small cell lung cancer, and advanced or recurrent solid tumors (excluding colon and rectal cancer) that are difficult to treat as standard. It has been approved in Japan by November 2023. In this study, we analyzed a case of using DB+TR for glioma at our center.

METHODS

DB+TR was applied to gliomas treated at our center from January 2018 to December 2023.

RESULTS

There were 10 patients, aged 32.7 years, and 3 males and 7 females. Pathological diagnoses was GBM 2, epithelioid GBM 2, anaplastic PXA 2, and anaplastic astrocytoma, glioneural tumor, gliosarcoma, and neuroepithelial tumor 1 respectively. IDH gene wild type and BRAF V600E mutation were observed in all cases. TERT mutations were observed in three C228T mutations and one C250T mutation. In 7 patients, temozolomide + radiotherapy 60Gy/30fraction was given as initial treatment. There were 9 cases in which DB+TR was used at the time of recurrence, and 1 case in which DB+TR was used in the initial treatment. As an adverse event (AE), DB+TR administration was discontinued in 1 case of intratumoral hemorrhage and 2 cases of skin rash. Skin rash was observed in other cases, but DB+TR administration could be continued with symptomatic treatment. The best effects were CR 5, PR 1 and SD 4. The median time from DB+TR use to recurrence was 21.3 (5 to 78.9) months. There were four deaths, and the median survival after discontinuation of DB+TR was 7.2 months (1.27 to 12.8).

DISCUSSION/CONCLUSION

For recurrent gliomas with BRAF V600E mutations, DB+TR showed good outcomes, although administration was discontinued due to AEs in three cases.