bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning delta-T noise for temperature bias estimation
Authors: Gerry Matthew , Wang Jonathan J. , Li Joanna , Shein-Lumbroso Ofir , Tal Oren , Segal Dvira
Published: February 2025

Delta-T shot noise is activated in temperature-biased electronic junctions, down to the atomic scale. It is characterized by a quadratic dependence on the temperature difference and a nonlinear relationship with the transmission coefficients of partially opened conduction channels. In this work, we demonstrate that delta-T noise, measured across an ensemble of atomic-scale junctions, can be utilized to estimate the temperature bias in these systems. Our approach employs a supervised machine learning algorithm to train a neural network, with input features being the scaled electrical conductance, the delta-T noise, and the mean temperature. Due to limited experimental data, we generate synthetic datasets, designed to mimic experiments. The neural network, trained on these synthetic data, was subsequently applied to predict temperature biases from experimental datasets. Using performance metrics, we demonstrate that the mean bias—the deviation of predicted temperature differences from their true value—is less than 1 K for junctions with conductance up to 4G0. Our study highlights that, while a single delta-T noise measurement is insufficient for accurately estimating the applied temperature bias due to noise contributions from other sources, averaging over an ensemble of junctions enables predictions within experimental uncertainties. This suggests that machine learning approaches can be utilized for estimation of temperature biases and similarly other stimuli in electronic junctions.
Numerical study on the dispersion of mechanical characteristics of granites: Based on a three-dimensional grain-based model and force chain analysis
Authors: Jiang Qichen , Zhang Qingsong , Zhang Tao , Yu Liyuan , Li Wei , Liu Yankai , Liu Jingwei
Published: February 2025

In this paper, a novel three-dimensional grain-based model based on particle flow code (GBM3D-PFC) is proposed, in which both the geometric division and mechanical property distinction of minerals are realized on the three-dimensional scale. A batch of cylindrical numerical samples with different sizes are constructed based on this model, and the uniaxial loading is then carried out. The position of mineral grains is variable within these samples. In addition, multilevel classification and quantitative analysis of a force chain network are also realized. The dispersion of mechanical characteristics of granites is explained from the point of microscopic mechanism information. This study found: the variation trend of stress-strain curves of the samples is consistent, and the dispersion of compressive strength and elastic modulus decreases with the increase in sample height L. The average value of force chains gradually approaches a stable value. The dispersion of it is almost the same as that of the macroscopic mechanical parameters. With the increase in L, the dispersion of the resistance to rupture of intragranular structures and intergranular structures decreases, that is, the stress level required to produce a single micro-crack is gradually stable, which is the fundamental reason for the decrease in the dispersion of the macro-mechanical parameters. With the improvement of computational efficiency, the quantitative analysis of a multilevel force chain network on the three-dimensional scale can be used in various engineering cases, such as the characterization of stress evolution of surrounding rocks during excavation and the strength estimation of damaged rock mass.
Band structure modulation of chalcogenide perovskite with Eu as A-site cation
Authors: Han Yanbing , Fang Jiao , Xing Xiaoyang , Gao Han , Zhang Jibin , Zhang Yuewen , Yuan Yifang , Yang Jie , Li Shunfang , Shi Zhifeng
Published: February 2025

Chalcogenide perovskites with distorted structures, such as BaZrS3 and SrZrS3, are promising photovoltaic materials due to their high stability, strong absorption, and excellent electrical transport properties. Researchers have explored BaZr1-xTixS3 and BaZrS3-xSex alloys to reduce their band gaps, allowing them to absorb lower-energy photons. However, the hexagonal structures of BaTiS3 and BaZrSe3, along with the incompatibility of Ti or Se atoms in BaZrS3, lead to phase separation in these alloys. In this work, using EuZrS3 and Sr0.7Eu0.3ZrS3 alloys as examples, we demonstrate that the band structure of chalcogenide perovskites can be tuned by using Eu as the A-site cation. In EuZrS3, the Eu 4f orbitals contribute to the valence band maximum, thereby raising the valence band and resulting in a narrow bandgap of 0.54 eV. Furthermore, due to the structural and atomic compatibility of Eu with SrZrS3, the Sr1-xEuxZrS3 alloy is designed to fine-tune the band structures of both SrZrS3 and EuZrS3. EuZrS3 also exhibits typical semiconducting characteristics, making it promising for potential optoelectronic devices.
Multiomics analysis unveils the cellular ecosystem with clinical relevance in aldosterone-producing adenomas with
KCNJ5
mutations
Authors: Yokomoto-Umakoshi Maki , Fujita Masamichi , Umakoshi Hironobu , Ogasawara Tatsuki , Iwahashi Norifusa , Nakatani Kohta , Kaneko Hiroki , Fukumoto Tazuru , Nakao Hiroshi , Haji Shojiro , Kawamura Namiko , Shimma Shuichi , Seki Masahide , Suzuki Yutaka , Izumi Yoshihiro , Oda Yoshinao , Eto Masatoshi , Ogawa Seishi , Bamba Takeshi , Ogawa Yoshihiro
Published: February 2025

Aldosterone-producing adenomas (APA), a major endocrine tumor and leading subtype of primary aldosteronism, cause secondary hypertension with high cardiometabolic risks. Despite potentially producing multiple steroid hormones, detailed cellular mechanisms in APA remain insufficiently studied. Our multiomics analysis focusing on APA with
KCNJ5
mutations, which represent the most common genetic form, revealed marked cellular heterogeneity. Tumor cell reprogramming initiated from stress-responsive cells to aldosterone-producing or cortisol-producing cells, with the latter progressing to proliferative stromal-like cells. These cell subtypes showed spatial segregation, and APA exhibited genomic intratumor heterogeneity. Among the nonparenchymal cells, lipid-associated macrophages, which were abundant in APA, might promote the progression of cortisol-producing and stromal-like cells, suggesting their role in the tumor microenvironment. Intratumor cortisol synthesis was correlated with increased blood cortisol levels, which were associated with the development of vertebral fractures, a hallmark of osteoporosis. This study unveils the complex cellular ecosystem with clinical relevance in APA with
KCNJ5
mutations, providing insights into tumor biology that could inform future clinical approaches.
Ensuring resilience in agri-food supply chains
Authors: Tsoulfas Giannis T.
Published: February 2025

Agri-food supply chains (AFSCs) are critical for global food security, but they have been facing challenging disruptions from climate change, pandemics, and geopolitical events. This review analyses how sustainability practices can enhance AFSC resilience and explore the trade-offs between sustainability initiatives and resilience strategies. The methodology for this review article involved a systematic literature search and content analysis approach to investigate the connections between sustainability and resilience in AFSCs. The systematic analysis of 28 papers reveals several key themes. A holistic and cyclical approach to sustainability and resilience in AFSCs allows practices to be adapted to changing conditions and ensures that sustainability efforts do not harm economic outcomes. Collaboration and stakeholder engagement are crucial for leveraging sustainability for resilience. Joint planning, information sharing, and customer integration can lead to better resource management and operational efficiency. Innovation, diversification, and adaptability are key to maintaining economic viability while pursuing sustainability and resilience. They can increase the value of end products, support local markets, and grow profitability in agriculture. Moreover, proposed strategies, policies, and conceptual frameworks for designing sustainable and resilient supply chains are reviewed. Focus is also drawn to the latest technologies that can help balance sustainability, resilience, and economic viability by enhancing decision making. In addition, shifting product demand from global to local suppliers is discussed as a way to reduce impacts from supply chain disruptions and revitalize local economies. Finally, the review emphasizes the importance of understanding trade-offs between sustainability initiatives and resilience strategies to develop integrated approaches.
ASPIRE: Iterative amortized posterior inference for Bayesian inverse problems
Authors: Orozco Rafael , Siahkoohi Ali , Louboutin Mathias , Herrmann Felix
Published: February 2025

Due to their uncertainty quantification, Bayesian solutions to inverse problems are the framework of choice in applications that are risk averse. These benefits come at the cost of computations that are in general, intractable. New advances in machine learning and variational inference (VI) have lowered this computational barrier by leveraging data-driven learning. Two VI paradigms have emerged that represent different tradeoffs: amortized and non-amortized. Amortized VI can produce fast results but due to generalizing to many observed datasets it produces suboptimal inference results. Non-amortized VI is slower at inference but finds better posterior approximations since it is specialized towards a single observed dataset. Current amortized VI techniques run into a sub-optimality wall that can not be improved without more expressive neural networks or extra training data. We present a solution that enables iterative improvement of amortized posteriors that uses the same networks architectures and training data. The benefits of our method requires extra computations but these remain frugal since they are based on physics-hybrid methods and summary statistics. Importantly, these computations remain mostly offline thus our method maintains cheap and reusable online evaluation while bridging the optimality gap between these two paradigms. We denote our proposed method ASPIRE - Amortized posteriors with Summaries that are Physics-based and Iteratively REfined. We first validate our method on a stylized problem with a known posterior then demonstrate its practical use on a high-dimensional and nonlinear transcranial medical imaging problem with ultrasound. Compared with the baseline and previous methods in the literature, ASPIRE stands out as an computationally efficient and high-fidelity method for posterior inference.
Calculations of positron scattering and annihilation from H-like ions
Authors: Mori Nicolas Antonio , Fursa Dmitry V , Bray Igor
Published: February 2025

The single-center convergent close-coupling (CCC) method is utilized to calculate positron scattering from H-like ions from He+. to F8+. Results for the normalized annihilation rate (Zeff) and the electron-loss, elastic, and bound-state excitation cross sections are obtained for energies up to 10 keV. Excellent agreement is found between present and previous theoretical Zeff results for He+, Li2+, B4+, and F8+. As there is no previous work for the remaining cross sections the results for electron-loss are presented alongside previous theory and experiment for incident electrons. The differences between these cross sections give an insight to the impact of the projectile charge on scattering from highly-charged ions.
Galactic gas models strongly affect the determination of the diffusive halo height
Authors: Luque Pedro De La Torre , Linden Tim
Published: February 2025

The height of the Milky Way diffusion halo, above which cosmic-rays can freely escape the galaxy, is among the most critical, yet poorly known, parameters in cosmic-ray physics. Measurements of radioactive secondaries, such as 10Be or 26Al, which decay equivalently throughout the diffusive volume, are expected to provide the strongest constraints. This has motivated significant observational work to constrain their isotopic ratios, along with theoretical work to constrain the cross-section uncertainties that are thought to dominate radioactive secondary fluxes. In this work, we show that the imprecise modelling of the Milky Way spiral arms significantly affects our ability to translate 10Be and 26Al fluxes into constraints on the diffusive halo height, biasing our current results. Utilizing state-of-the-art spiral arms models we produce new predictions for the 10Be and 26Al fluxes that motivate upcoming measurements by AMS-02 and HELIX.
Numerical analysis of melting domain walls and their gravitational waves
Authors: Dankovsky I. , Ramazanov S. , Babichev E. , Gorbunov D. , Vikman A.
Published: February 2025

We study domain walls (DWs) arising in field theories where Z
2-symmetry is spontaneously broken by a scalar expectation value decreasing
proportionally to the Universe temperature. The energy density of such melting DWs redshifts sufficiently fast not to overclose the Universe.
For the first time, evolution of melting DWs and the resulting gravitational waves (GWs) is investigated numerically using lattice simulations. We show that formation of closed melting DWs during radiation domination is much more efficient compared to the scenario with constant tension DWs. This suggests that it can be the main mechanism responsible for reaching the scaling regime similarly to the case of cosmic strings. However, the scaling behaviour of
melting DWs is observed, provided only that the initial scalar field fluctuations are not very large. Otherwise, simulations reveal violation of the scaling law, potentially of the non-physical origin. The spectrum of GWs emitted by melting DWs is also significantly different from that of constant tension DWs. Whether the system has reached scaling or not, the numerical study reveals a GW spectrum described in the infrared by the spectral index n ≈ 1.6 followed by the causality tail. We attribute the difference from the value n = 2 predicted in our previous studies to a finite lifetime of the DW network. Notably, the updated index is still in excellent agreement with the recent findings by pulsar timing arrays, which confirms that melting DWs can be responsible for the observed (GW) signal. We also point out that results for evolution of melting DWs in the radiation-dominated Universe are applicable to constant tension DW evolution in the flat spacetime.
Imprints of black hole charge on the precessing jet nozzle of M87*
Authors: Meng Xiang-Cheng , Wang Chao-Hui , Wei Shao-Wen
Published: February 2025

The observed jet precession period of approximately 11 years for M87* strongly suggests the presence of a supermassive rotating black hole with a tilted accretion disk at the center of the galaxy. By modeling the motion of the tilted accretion disk particle with the spherical orbits around a Kerr-Newman black hole, we study the effect of charge on the observation of the precession period, thereby exploring the potential of this strong-gravity observation in constraining multiple black hole parameters. First, using the Hamiltonian formalism, we derive the equations of motion for spherical orbits, along with the general forms of energy and angular momentum, in the general stationary axisymmetric black hole spacetime. Subsequently, taking the Kerr-Newman black hole as a specific example, we study the effect of charge on spherical orbits and find that the precession period increases with increasing charge. Furthermore, incorporating the constraints of EHT on the black hole charge, we utilize the observed M87* jet precession period to constrain the relationship between the spin, charge, and warp radius, specifically detailing the correlations between each pair of these three quantities. To further refine constraints on the charge, we explore the negative correlation between the maximum warp radius and charge. A significant result shows that the gap between the maximum warp radius of the prograde and retrograde disk decrease with the black hole charge. If the warp radius is provided by other observations, different constraints on the charge can be derived for the prograde and retrograde cases. Finally, we investigate the size of the inner disk. By making use of current observations, our study reveals that the size of the inner disk increases with the charge and spin, and the prograde disk is always larger than the retrograde one. These results provide significant effects of charge in the physics around M87*.
Investigation of heavy particle radioactivity and spontaneous fission of even-Z superheavy nuclei*
Authors: Sandhu Kirandeep , Kaur Gurjit , Sharma Manoj K.
Published: February 2025

The preformed cluster model (PCM) is applied to investigate the heavy particle radioactivity (HPR) and spontaneous fission (SF) processes for even-Z superheavy nuclear systems. Different proximity potentials are used to calculate the decay half-lives of

nuclei. The fragmentation potential and preformation distribution suggest that SF is the major contributor up to

, and HPR starts competing for heavier nuclei. The heavy cluster emission is supported by Pb-magicity, whereas SF is reinforced owing to the deformations of fission fragments. The heavy cluster decay half-lives (log

TC
) are calculated using the PCM and are compared with the estimates of the analytical super asymmetric fission (ASAF) model. The calculated log

TC
values agree well with the ASAF measurements when using the Prox-00 and Mod Prox-00 versions of potentials. However, Prox-77, Prox-88, and Prox-BW-91 are not appropriate to address the log

TC
for

nuclei. To resolve this, we include Z-dependence in the radius parameters. Interestingly, the half-lives match the ASAF data after the inclusion of Z-dependence. The branching ratios are also calculated for superheavy nuclei and compared with the estimates of unified description (UD) formula, universal curve (UNIV), universal decay law (UDL), Horoi formula, and ASAF measurements. Furthermore, the SF half-lives (

) of

Cn,

Cn,

Fl, and

Fl superheavy nuclei are estimated through various proximity potentials. Among them, Prox-00 is appropriate for addressing the experimental data. Using this potential, the SF half-lives are estimated through the PCM for

isotopes at different neck-length parameters. Finally, the scaled total kinetic energy (TKE) values are compared with the available data.
Benchmarking of CST and Trak in the simulation of an electron gun for a future C6+ ion source
Authors: Etxebarria J. , Moreno G. , Obradors D. , Oliver C. , Pikin A. , Battaglia C. , Carmona J.M. , Tato A.
Published: February 2025

This study benchmarks the CST Studio Suite and Trak codes in simulating an electron gun for a future C6+ hadrontherapy installation. CST Studio Suite offers 3D simulation capabilities, allowing detailed modelling of complex geometries and electromagnetic fields. Trak, on the other hand, offers efficient 2D simulations, which can significantly reduce computational time while still providing valuable results.

These studies are being conducted in the framework of a project dedicated to the design of the initial stage of a C6+ hadrontherapy linac. The electron gun studied is based on the MEDeGUN developed at CERN. This study provides an overview of the results obtained so far and outlines plans for future improvements and development.
Clinical Indicator Analysis
Authors: Zhu Fu-Kuan , Gao Ding-Zhi , Xiang Feng , Hu Hao , Wen Ya-Feng , Deng Zhong-Liang , Wu Yuan-Yuan , Niu Yu-Tian , Chu Lei , Sheng Xiao-Min , Shi Lei
Published: February 2025

Study Design.

Retrospective case-control study.

Objective.

To examine the differences in various clinical indicators between Kümmell’s disease (KD) and osteoporotic vertebral compression fractures (OVCF), in order to assist in the diagnosis of KD and provide a foundation for further analysis of its risk factors.

Summary of Background Data.

The mechanisms underlying the progression of OVCF to KD remain unclear, and research analyzing the indicators between the two conditions is still limited.

Patients and Methods.

We conducted a retrospective analysis of 21 males and 59 females patients diagnosed with KD, among those admitted for OVCF at our hospital from January 2018 to January 2023. We defined all KD patients as the kümmell group (K group). In the same period, we randomly selected 71 males and 301 females patients with OVCF as OVCF group (O group). We conducted statistical descriptions and analyses comparing both groups based on sex, bone density, age, serum calcium, serum phosphorus, endogenous creatinine clearance rate (Ccr), glomerular filtration rate (GFR), alkaline phosphatase (ALP), total protein (TP), albumin, (1, 25-(OH)2 D3), calcitonin, parathyroid hormone (PTH), N-mid osteocalcin (N-MID-OT), β-isomerized C-terminal telopeptides (β-CTX), procollagen 1 N-terminal propeptide (P1NP), body mass index (BMI), history of fragility fracture (HFF), hypertension, diabetes, and coronary heart disease.

Results.

We found that the albumin level in K group (P<0.001) was significantly lower than that in the O group, and the serum phosphorus (P=0.002), PTH (P=0.037), and HFF (P<0.001) in K group were significantly higher than those in the O group.

Conclusion.

Patients with KD have lower albumin levels, higher blood phosphorus levels and PTH, and a greater likelihood of a HFF compared to those with OVCF. If patients with low back pain exhibit these issues, timely medical attention is essential to rule out OVCF and prevent its progression to KD.
Cardiovascular Risk Profile of Nivolumab Anti-cancer Therapy
Authors: Qureshi Zaheer , Zaheer Zaofashan , Asghar Zoha , Bakhtiar Muhammad , Fatima Eeshal , Altaf Faryal
Published: February 2025

Objectives:

Immune checkpoint inhibitors (ICI) upregulate host antitumor immunity, proving efficacy across diverse tumor types. Currently approved ICI treatment primarily targets the programmed cell death receptor 1 (PD-1) and its ligand PD-L1, and cytotoxic T lymphocyte-antigen 4 (CTLA-4). Nivolumab is a monoclonal antibody that targets the human PD-1 receptor and is an entirely human immunoglobulin G4 (IgG4), approved by the FDA for various cancers like advanced melanoma, metastatic renal cell carcinoma, Hodgkin lymphoma, and advanced lung carcinoma. This review will summarise and discuss the recent literature on cardiotoxicity associated with nivolumab therapy.

Methods:

We searched online databases like PubMed, Scopus, Google Scholar, and Embase for articles related to Nivolumab.

Results:

Cardiotoxicity with ICI use is most commonly represented as myocarditis. Patients present with complaints of shortness of breath, palpitations, edema, and fatigue. Takotsubo cardiomyopathy, or broken heart syndrome, is characterized by systolic dysfunction of the left ventricle, mimicking a myocardial infarction but without associated coronary ischemia and with minimal elevation of cardiac enzymes. In the CHECKMATE-037 trial, ventricular arrhythmias occurred in <10% of those who received nivolumab. In a retrospective analysis of patients treated with ICI (predominantly nivolumab monotherapy) for lung cancer, 11% of the patients developed major adverse cardiac events, including myocarditis, non-ST-segment elevated myocardial infarction, supraventricular tachycardia, and pericardial disorders.

Conclusion:

Close collaboration between cardiology and oncology specialists is crucial for early detection and effective management of cardiac complications, enhancing the safety of nivolumab anticancer therapy.
Impact of Minimal Residual Diseases Status and Depth of Response on Survival Outcomes in Blinatumomab-Treated Acute Lymphoblastic Leukemia
Authors: Jamil Abdur , Qureshi Zaheer , Riaz Rida , Akram Hamzah , Jamil Rohma , Kichloo Asim , Selene Insija Ilyas
Published: February 2025

Objectives:

Acute lymphoblastic leukemia (ALL) is a common hematological malignancy that occurs due to blockage of B-lymphocyte maturation at an early stage of development and differentiation. The Food and Drug Administration approved blinotumomab to manage relapsed/refractory ALL (R/R ALL). This review aimed to determine the comparative efficacy of blinatumomab in treating R/R ALL.

Methods:

Two reviewers searched 3 electronic databases, PubMed, ScienceDirect, and CENTRAL, for all relevant articles published until July 2024. All the articles that met the inclusion criteria were included in the review.

Results:

Four hundred thirty-seven articles were found from the electronic search; however, only 21 articles met the inclusion criteria. A pooled analysis of the outcomes found that blinatumomab resulted in an improvement in both the OS (HR: 0.65; 95% CI: 0.51, 0.82; P=0.0003) and the DFS (HR: 0.57; 95% CI: 0.41, 0.80; P=0.001). Further analysis showed that the CR rate and MRD response of ALL patients to blinatumomab was 51.6% (95% CI: 48.5%, 54.6%; P=0.319) and 64.6% (95% CI: 53.4%, 74.3%; P=0.011), respectively. The safety analysis indicated that the incidence of serious AEs was comparable in patients receiving blinotumomab and those receiving standard chemotherapy (OR: 1.34; 95% CI; 0.91, 1.97; P=0.14).

Conclusions:

The findings show that blinatumomab is superior to standard chemotherapy in improving the OS and DFS of patients with R/R ALL. Furthermore, it has a more favorable safety profile, making it an effective alternative to conventional chemotherapy for managing R/R ALL.
From Scalp Flaps to Follicular Units: A Historical Perspective on Hair Transplantation Techniques
Authors: Moeckel Camille , Chacharidakis Georgios , Balasis Stavros , Queen Dawn , Avram Marc R. , Panagiotopoulou Gianna
Published: February 2025

BACKGROUND

Hair has long held cultural and psychosocial significance, symbolizing health, status, and identity. Hair loss impacts quality of life, self-esteem, and psychological well-being. While treatments like minoxidil and finasteride exist, they often yield limited results. Hair transplantation (HT), first demonstrated by Johann Friedrich Dieffenbach in 1822, has evolved into the most effective hair restoration method. Since its inception in 1975, Dermatologic Surgery has been a main source for groundbreaking publications from major players in the field, while also playing a pivotal role in documenting the history of HT.

OBJECTIVE

This mini review examines the historical evolution of HT techniques over the past 200 years, highlighting their advantages and limitations.

MATERIALS AND METHODS

A literature search was conducted using PubMed and Google Scholar with the term “hair transplantation techniques.” Relevant sources were reviewed to extract information on technique development and historical origins.

RESULTS

Key pioneers such as Dieffenbach, Menahem Hodara, and Shoji Okuda laid the groundwork for modern HT. Milestones include punch grafting, follicular unit transplantation (FUT), and follicular unit extraction (FUE). FUT emphasized natural follicular grouping, while FUE introduced minimally invasive methods with faster recovery and better aesthetics. Recent advancements include robotic-assisted procedures and bioengineered follicles, reflecting a shift toward precision and patient-centered care.

CONCLUSION

The continuous evolution of HT techniques underscores its position as the most effective method for hair restoration, particularly in androgenetic alopecia cases.
Integrative transcriptome profiling elucidates molecular and immunovascular characteristics of macrotrabecular hepatocellular carcinoma
Authors: Taniai Tomohiko , Shimada Shu , Akiyama Yoshimitsu , Hatano Megumi , Yasukawa Koya , Igarashi Yosuke , Tsukihara Shu , Tanji Yoshiaki , Kodera Keita , Okazaki Kohei , Haruki Koichiro , Nara Atsushi , Yagi Kohei , Akahoshi Keiichi , Ban Daisuke , Asahina Yasuhiro , Ikegami Toru , Tanabe Minoru , Tanaka Shinji
Published: February 2025

Background and Aims:

Recent advances in single-cell RNA sequencing (scRNA-seq) technologies have enabled us to clarify gene regulatory networks and immune cell compositions. In this study, integration of large-scale bulk and single-cell datasets refined hepatocellular carcinoma (HCC) classification and shed light on the characteristics of its aggressive subtype.

Approach and Results:

Single-cell analysis of 228,564 live cells from six scRNA-seq datasets identified five major clusters of HCC cells with high mitotic activity (Cluster 1), activated Wnt/β-catenin signaling (Cluster 2), elevated glycolysis (Cluster 3) and lipogenesis (Clusters 4 and 5). Aggressive HCC subtype defined in bulk RNA-seq analysis of 691 tumor samples comprised a combination of Cluster 1 with Clusters 3, 4 or 5. Gene regulatory network analysis and gene set enrichment analysis highlighted the essential roles of p53 and MYC in aggressive HCC/Cluster 1, and cell composition analysis elucidated T cell depletion as an immune resistance mechanism. In a syngeneic mouse model, Trp53 knockout and MYC overexpression caused highly mitotic, tumorigenic and metastatic phenotypes, characterized by a macrotrabecular (MT) pattern, vascular encapsulation (VE) and T cell exclusion. Angiogenesis inhibition disrupted MT/VE formation, resulting in T cell recruitment, and its combination with immune checkpoint blockade achieved remission.

Conclusions:

Single-cell analysis has deepened our understanding of the molecular mechanism and tumor microenvironment in aggressive HCC. The combination of targeting tumor vasculature and blocking immune checkpoints represents a promising therapeutic strategy for this subtype.
Day-to-day blood pressure variability in older persons – optimizing measurement
Authors: Palsma Tanya , Claassen Jurgen A.H.R. , Richard Edo , De Heus Rianne A.A.
Published: February 2025

Background:

Higher blood pressure variability (BPV) is associated with adverse clinical outcomes but lack of standardized methodology hampers clinical translation. Day-to-day BPV seems most promising for an older population, especially those with cognitive impairment. This study aimed to determine the optimal number of measurements for obtaining day-to-day BPV in this population.

Methods:

We included 127 patients attending the geriatric outpatient memory clinic, who measured blood pressure for seven days, morning and evening. Blood pressure measurements of day one were discarded and the coefficient of variation was calculated to assess BPV. Concordance between 7-day BPV (CV7days) and a reduced number of measurement days (CV6days – CV3days) was analysed with Bland–Altman plots, intraclass correlation coefficient (ICC), and an a priori determined threshold of a 95% confidence interval (CI) with a lower bound of 0.75.

Results:

The mean age was 74.6 ± 8.6 years, 49% were female, and had dementia or mild cognitive impairment in 37% and 33% respectively. Reducing the number of measurement days resulted in wider limits of agreement. Concordance decreased when reducing measurement days and reached our predefined threshold with four measurement days (ICC = 0.91, 95% CI = 0.87 – 0.93). BPV derived from five measurement days showed a similar relationship with diagnosis as our reference BPV value obtained with seven days.

Conclusion:

Our results suggest that systolic home blood pressure should be measured in the morning and evening for at least five consecutive days in duplicate to obtain reliable day-to-day BPV values in older adults with cognitive complaints.
Prediction of incidence of hypertension in France and associated factors: results from the CONSTANCES cohort
Authors: Cheddani Lynda , Lelong Hélène , Goldberg Marcel , Zins Marie , Blacher Jacques , Kab Sofiane
Published: February 2025

Introduction:

Estimating hypertension incidence and improving screening in general population could enhance blood pressure control and decrease cardiometabolic risks. Identifying those likely to develop hypertension is essential. Our study focused on predicting onset hypertension and its incidence based on initial characteristics.

Methods:

We utilized data from the French prospective CONSTANCES cohort, including volunteers assessed twice over 5 years up to 31 December 2019, who were initially free from hypertension. Hypertension was defined as having a SBP at least 140 mmHg or DBP at least 90 mmHg during the second checkup or if antihypertensive medication was prescribed. We calculated annual incidence rates among subgroups and used machine learning models to identify predictors of hypertension. The impact of changes in BMI was analyzed using logistic regression.

Results:

Of the 11 112 participants (average age 47.5 ± 12 years), 1929 (17.4%) developed hypertension within an average of 5.2 years, with 383 on medication. The incidence rate was 3.4 new cases per 100 person-years, rising with age and consistently higher in men (4.3 vs. 2.8). A blood pressure (BP) threshold of 130 mmHg predicted 70% of new cases. One-point BMI reduction significantly reduced hypertension risk by 16%, regardless of initial BMI and SBP levels.

Conclusion:

The study reports a notable hypertension incidence of 3.4 new cases per 100 person-years, particularly among those with SBP over 130 mmHg, highlighting the need for regular screening. Early diagnosis and control can mitigate hypertension's adverse effects, emphasizing the crucial role of preventive measures like BMI reduction.
Atypical Autofluorescence Findings in Geographic Atrophy: The Influence of Age-Related Choroidal Atrophy
Authors: Faes Livia , Jung Jesse J. , Sorenson John , Freund K. Bailey
Published: February 2025

Purpose:

To describe atypical fundus autofluorescence (FAF) patterns in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) with associated age-related choroidal atrophy (ARCA).

Methods:

Multimodal imaging of two cases using (pseudo-)color fundus photography, optical coherence tomography (OCT), fluorescein and indocyanine green angiography, and FAF employed with blue- and green excitation wavelengths on several devices (Spectralis, Heidelberg and (ultra-)widefield [UWF] FAF [California, Optos and EIDON, iCare]).

Results:

Two female patients, with foveal-involving GA secondary to AMD, were assessed. All eyes demonstrated concurrent features indicative of ARCA on multimodal imaging including a paucity of choroidal vasculature, reduced choroidal pigmentation, macular pigmentary changes, peripapillary atrophy, and subretinal drusenoid deposits. Clinically, progression of GA with coalescence of lobular lesions was observed. Notably, UWF FAF with green-(California) and blue excitation wavelengths (California and EIDON) revealed atypical patterns characterized by isofluorescent FAF signals (indistinguishable from surrounding tissue) or hyperautofluorescent GA lesions. In these cases, blue excitation wavelengths were more effective than green light for delineating GA, owing to increased contrast from hypoautofluorescence related to macular pigment surrounding the lesion.

Conclusion:

In patients with GA and concomitant ARCA, atypical FAF patterns on UWF imaging complicate the accurate delineation and monitoring of GA. Atypical FAF patterns appear due to the properties of the confocal apertures and postprocessing features of UWF imaging that allow for the detection of scleral autofluorescence in patients with reduced choroidal vasculature, pigment and thickness. In patients with concomitant ARCA, multimodal imaging plays a crucial role in precisely identifying and tracking GA progression.
A rare concurrence of acute appendicitis with Meckel’s diverticulitis: a case report
Authors: Bastakoti Aashish , Khatiwada Abhikanta , Neupane Nischal , Bastakoti Roshani , Bastakoti Anish , Kc Sharada
Published: February 2025

Background:

Meckel’s diverticulitis is the inflammation of Meckel’s diverticulum (MD), a common congenital structural abnormality of the gastrointestinal tract. The simultaneous occurrence of Meckel’s diverticulitis with acute appendicitis is extremely rare.

Case presentation:

A 17-year-old male presented with acute abdominal pain and vomiting, accompanied by tenderness in the right iliac fossa. Laboratory investigations revealed neutrophilia and an elevated leukocyte count, while ultrasound findings were consistent with acute appendicitis. The patient underwent an emergency open appendectomy, during which an inflamed appendix was removed. Incidentally, an inflamed MD was also discovered and managed conservatively.

Discussion:

Acute appendicitis and Meckel’s diverticulitis share overlapping clinical and imaging features, making preoperative diagnosis difficult, thereby making intraoperative evaluation essential. The management of Meckel’s diverticulitis varies depending on the patient’s condition and clinical judgment.

Conclusion:

Given the difficulty in preoperative diagnosis of Meckel’s diverticulitis, surgeons should routinely assess for MD during appendectomies, even when acute appendicitis is confirmed. Failing to identify and manage Meckel’s diverticulitis may lead to complications and adversely affect patient outcomes.
The role of advocacy and policy in advancing global neurosurgery
Authors: Abdul-Rahman Toufik , Badar Sarah M. , Ranganathan Sruthi , Nicholas Aderinto , Tan Joecelyn Kirani , Faith Ogungbemi Evelyn , Kundu Mrinmoy , Wireko Andrew Awuah , Ali Anam Sayed Mushir , Atallah Oday , Horbas Viktoriia , Teslyk Tetiana P. , Bumeister Valentyna
Published: February 2025

Global neurosurgery has witnessed transformative developments in advocacy and policy aimed at overcoming the barriers that hinder equitable access to neurosurgical care. This paper reveals the stark disparities faced by low- and middle-income countries (LMICs) with an annual burden of 5 million affected individuals. Despite these challenges, the emergence of global neurosurgery stands as a beacon of hope, aspiring to deliver timely, safe, and affordable neurosurgical care. Advocacy and policy play pivotal roles in this endeavour, exemplified by initiatives, like National Surgical, Obstetrics, and Anesthesia Plans (NSOAPs) and Global Neurosurgery Initiatives (GNI), addressing accessibility, training, and disparities. Collaborations between diverse entities and interdisciplinary approaches gain prominence, fostering comprehensive advocacy and policy frameworks. A resolute commitment to equity is discernible, propelling policies toward universal access to neurosurgical care. However, crucial challenges, such as limited resources, awareness gaps, complex political landscapes, data deficiencies, and insufficient international collaborations, must be addressed to see the full potential of these initiatives. While challenges persist, progress is evident through collaborative efforts, technological advancements, and evolving policy landscapes, promising a trajectory toward accessible, safe, and affordable neurosurgical care for all.
The development and construction of the Shanghai Museum of the Royal Asiatic Society during the Period of Republic of China: a study centred on Arthur de Carle Sowerby (1923–1946)
Authors: Fan Liyuan
Published: February 2025

In the late nineteenth and early twentieth centuries, natural history gained popularity among the Western public, and museums became one of the central institutions in people’s cultural lives. Within this context, the British naturalist Arthur de Carle Sowerby (1885–1954) was committed to building a cultural centre in Shanghai for facilitating the dissemination and popularization of natural history. Under his advocacy, preparation and management, the Shanghai Museum of the Royal Asiatic Society (RAS) was rebuilt in 1933 and subsequently prospered, becoming one of the most important cultural institutions in Shanghai at the time. This article investigates the original reasons for Sowerby’s participation in the rebuilding of the Shanghai Museum, as well as his management and administration of the museum. It reveals his important role in the restoration and successful development of the Shanghai Museum, analysing the development and spread of Western natural history in Shanghai in the modern era and its impact on the city’s culture.
Reducing blood culture contamination: an environmental imperative
Authors: Gregg Sophie , Purcell Niamh , Doyle Maeve , Chan Grace
Published: February 2025

Blood culture (BC) investigation remains the gold standard for the diagnosis of bloodstream infections. However, BC contamination can have clinical implications for the patient, cost implications for service providers and less well-documented, environmental impacts. Efforts to reduce BC contamination are a long-standing theme in quality improvement initiatives in emergency departments (EDs) and hospitals, prompted by hospital costs, healthcare inefficiencies and antimicrobial stewardship efforts. The WHO’s global analysis of healthcare waste in the context of COVID-19 has reported that tens of thousands of tonnes of extra medical waste were produced from the response to the COVID-19 pandemic, basing its estimates on the quantity of personal protective equipment. Additionally, recent literature has also shown increased BC contamination rates during the COVID-19 pandemic. We performed a retrospective review of the trend of BC contamination during the COVID-19 pandemic in our institution’s ED. We further discuss some of the potential implications of BC contamination, including potential environmental, economic and efficiency implications.
Biaxial testing and sensory texture evaluation of plant-based and animal deli meat
Authors: Pierre Skyler R. St. , Sibley Lauren Somersille , Tran Steven , Tran Vy , Darwin Ethan C. , Kuhl Ellen
Published: February 2025

Animal agriculture is one of the largest contributors to global carbon emissions. Plant-based meats offer a sustainable alternative to animal meat; yet, people are reluctant to switch their diets and spending habits, in large due to the taste and texture of plant-based meats. Deli meat is a convenient form of protein commonly used in sandwiches, yet little is known about its material or sensory properties. Here we performed biaxial testing with multiple different stretch ratios of four plant-based and four animal deli meats and fit accurate material models to the resulting stress-stretch data. Strikingly, the plant-based products, turkey, ham, deli, and prosciutto, with stiffnesses of 378 ± 15 kPa, 343 ± 62 kPa, 213 ± 25 kPa, and 113 ± 56 kPa, were more than twice as stiff as their animal counterparts, turkey, chicken, ham, and prosciutto, with 134 ± 46 kPa, 117 ± 17 kPa, 117 ± 21 kPa, and 49 ± 21 kPa. In a complementary sensory texture survey, n = 18 participants were able to correlate the physical stiffness with the sensory brittleness, with Spearman’s correlation coefficient ofρ= 0.857 andp= 0.011, but not with the sensory softness or hardness. Notably, the participants perceived all four plant-based products as less fibrous, less moist, and less meaty than the four animal products. Our study confirms the common belief that plant-based products struggle to meet the physical and sensory signature of animal deli meats. We anticipate that integrating rigorous mechanical testing, physics-based modeling, and sensory texture surveys could shape the path towards designing delicious, nutritious, and environmentally friendly meats that mimic the texture and mouthfeel of animal products and are healthy for people and for the planet. Data and code are freely available athttps://github.com/LivingMatterLab/CANN.
Dynamic Modeling of Cell Cycle Arrest Through Integrated Single-Cell and Mathematical Modelling Approaches
Authors: Cortés-Ríos Javiera , Rodriguez-Fernandez Maria , Sorger Peter Karl , Fröhlich Fabian
Published: February 2025

Highly multiplexed imaging assays allow simultaneous quantification of multiple protein and phosphorylation markers, providing a static snapshots of cell types and states. Pseudo-time techniques can transform these static snapshots of unsynchronized cells into dynamic trajectories, enabling the study of dynamic processes such as development trajectories and the cell cycle. Such ordering also enables training of mathematical models on these data, but technical challenges have hitherto made it difficult to integrate multiple experimental conditions, limiting the predictive power and insights these models can generate. In this work, we propose data processing and model training approaches for integrating multiplexed, multi-condition immunofluorescence data with mathematical modelling. We devise training strategies that are applicable to datasets where cells exhibit oscillatory as well as arrested dynamics and use them to train a cell cycle model on a dataset of MCF-10A mammary epithelial exposed to cell-cycle arresting small molecules. We validate the model by investigating predicted growth factor sensitivities and responses to inhibitors of cells at different initial conditions. We anticipate that our framework will generalise to other highly multiplexed measurement techniques such as mass-cytometry, rendering larger bodies of data accessible to dynamic modelling and paving the way to deeper biological insights.
DifferentialO-Glc elongation on the specific EGF repeat within a ligand binding domain regulates NOTCH1 signaling
Authors: Tsukamoto Yohei , Aoki Kazuhiro , Saiki Wataru , Tsukamoto Natsumi , Kato Koki , Hosokawa Yohei , Sato Rie , Fujita Yuki , Fukazawa Kana , Kurebayashi Yuuki , Urata Yusuke , Uchiyama Sae , Wang Weiwei , Minami Akira , Takahashi Tadanobu , Tiemeyer Michael , Narimatsu Yoshiki , Okajima Tetsuya , Takeuchi Hideyuki
Published: February 2025

Three types ofO-linked glycosylation -O-glucose,O-fucose, andO-N-acetylglucosamine - are crucial for the function of Notch receptors, which regulates critical cell fate determination processes in a wide variety of contexts.O-Glucose glycans are added to serine residues located between the first and second conserved cysteines within the epidermal growth factor (EGF) -like repeats in the Notch extracellular domain. Previously,O-glucose glycans were shown to be extended to a trisaccharide structure with two xyloses via an α1-3 linkage. Our recent studies, however, indicated that theO-glucose glycan on NOTCH1 EGF10 can be extended by hexose and Neu5Ac. Here, we demonstrated that this hexose- and Neu5Ac-extended glycan has a 3’-sialyllactose-like structure synthesized by specific members of two isoenzyme families, B4GALT1 and ST3GAL4. Using mass spectrometry, we identified this modification exclusively on NOTCH1 EGF10 and NOTCH3 EGF9 (equivalent to NOTCH1 EGF10), with no detection in any other EGF domains in NOTCH1-3. Sequence comparison and mutagenesis experiments identified one amino acid at position -2 of the fourth cysteine in the EGF domain as crucial for the galactose elongation ofO-glucose glycans. We further demonstrated that this site-specific elongation ofO-glucose on NOTCH1 EGF10 significantly impact ligand binding and signal transduction of NOTCH1. Our findings contribute to the understanding of the intricate regulatory mechanisms of Notch receptor function mediated by distinct positions and structures ofO-glycans.

Significance Statement

Notch, a signaling receptor critical for development, differentiation, and homeostasis in multicellular organisms, undergoes multiple post-translational glycan modifications to regulate its function. WhileO-glucose glycan elongation by xylose was previously known, we identified anO-glucose glycan extended by galactose and Neu5Ac on specific epidermal growth factor (EGF) -like repeats of certain Notch paralogs, NOTCH1 and NOTCH3. As far as we know, this structure has not been reported on any other proteins. We identify the enzymes involved in the biosynthesis of this glycan and demonstrate that modifications at a specific site on Notch direct receptor functions, including ligand binding and Notch signaling.