bluuebunny/crossref_metadata_2025_split huggingface dataset:
SQM2.20: Semiempirical quantum-mechanical scoring function yields DFT-quality protein–ligand binding affinity predictions in minutes
Authors: Pecina Adam , Fanfrlík Jindřich , Lepšík Martin , Řezáč Jan 
Published: February 2024

AbstractAccurate estimation of protein–ligand binding affinity is the cornerstone of computer-aided drug design. We present a universal physics-based scoring function, named SQM2.20, addressing key terms of binding free energy using semiempirical quantum-mechanical computational methods. SQM2.20 incorporates the latest methodological advances while remaining computationally efficient even for systems with thousands of atoms. To validate it rigorously, we have compiled and made available the PL-REX benchmark dataset consisting of high-resolution crystal structures and reliable experimental affinities for ten diverse protein targets. Comparative assessments demonstrate that SQM2.20 outperforms other scoring methods and reaches a level of accuracy similar to much more expensive DFT calculations. In the PL-REX dataset, it achieves excellent correlation with experimental data (average R2 = 0.69) and exhibits consistent performance across all targets. In contrast to DFT, SQM2.20 provides affinity predictions in minutes, making it suitable for practical applications in hit identification or lead optimization.
Shape-recovery of implanted shape-memory devices remotely triggered via image-guided ultrasound heating
Authors: Zhu Yang , Deng Kaicheng , Zhou Jianwei , Lai Chong , Ma Zuwei , Zhang Hua , Pan Jiazhen , Shen Liyin , Bucknor Matthew D. , Ozhinsky Eugene , Kim Seungil , Chen Guangjie , Ye Sang-ho , Zhang Yue , Liu Donghong , Gao Changyou , Xu Yonghua , Wang Huanan , Wagner William R. 
Published: February 2024

AbstractShape-memory materials hold great potential to impart medical devices with functionalities useful during implantation, locomotion, drug delivery, and removal. However, their clinical translation is limited by a lack of non-invasive and precise methods to trigger and control the shape recovery, especially for devices implanted in deep tissues. In this study, the application of image-guided high-intensity focused ultrasound (HIFU) heating is tested. Magnetic resonance-guided HIFU triggered shape-recovery of a device made of polyurethane urea while monitoring its temperature by magnetic resonance thermometry. Deformation of the polyurethane urea in a live canine bladder (5 cm deep) is achieved with 8 seconds of ultrasound-guided HIFU with millimeter resolution energy focus. Tissue sections show no hyperthermic tissue injury. A conceptual application in ureteral stent shape-recovery reduces removal resistance. In conclusion, image-guided HIFU demonstrates deep energy penetration, safety and speed.
Senolytics: from pharmacological inhibitors to immunotherapies, a promising future for patients’ treatment
Authors: Lelarge V. , Capelle R. , Oger F. , Mathieu T. , Le Calvé B. 
Published: February 2024

AbstractThe involvement of cellular senescence in the initiation and propagation of diseases is clearly characterized, making the elimination of senescent cells essential to treat age-related diseases. The development of senolytic drugs demonstrated that targeting these cells limits the deterioration of patients’ condition, by inducing apoptosis. Nevertheless, the first generations of senolytics which has been developed displayed their activities through specific mechanisms and demonstrated several limitations during clinical development. However, the rational to eliminate senescent cells remains evident, with the necessity to develop specific therapies in a context of diseases and tissues. The evolutions in the field of drug discovery open the way to a new generation of senolytic therapies, such as immunological approaches (CAR-T cells, Antibody-Drug Conjugated or vaccines), which require preliminary steps of research to identify markers specifically expressed on senescent cells, demonstrating promising specific effects. Currently, the preclinical development of these strategies appears more challenging to avoid strong side effects, but the expected results are commensurate with patients’ hopes for treatments. In this review, we highlight the fact that the classical senolytic approach based on drug repurposing display limited efficacy and probably reached its limits in term of clinical development. The recent development of more complex therapies and the extension of interest in the domain of senescence in different fields of research allow to extend the possibility to discover powerful therapies. The future of age-related diseases treatment is linked to the development of new approaches based on cell therapy or immunotherapy to offer the best treatment for patients.
Unravelling ultralow thermal conductivity in perovskite Cs2AgBiBr6: dominant wave-like phonon tunnelling and strong anharmonicity
Authors: Zheng Jiongzhi , Lin Changpeng , Lin Chongjia , Hautier Geoffroy , Guo Ruiqiang , Huang Baoling 
Published: February 2024

AbstractUnderstanding the lattice dynamics and heat transport physics in the lead-free halide double perovskites remains an outstanding challenge due to their lattice dynamical instability and strong anharmonicity. In this work, we investigate the microscopic mechanisms of anharmonic lattice dynamics and thermal transport in lead-free halide double perovskite Cs2AgBiBr6 from first principles. We combine self-consistent phonon calculations with bubble diagram correction and a unified theory of lattice thermal transport that considers both the particle-like phonon propagation and wave-like tunnelling of phonons. An ultra-low thermal conductivity at room temperature (~0.21 Wm−1K−1) is predicted with weak temperature dependence( ~ T−0.34), in sharp contrast to the conventional ~T−1 dependence. Particularly, the vibrational properties of Cs2AgBiBr6 are featured by strong anharmonicity and wave-like tunnelling of phonons. Anharmonic phonon renormalization from both the cubic and quartic anharmonicities are found essential in precisely predicting the phase transition temperature in Cs2AgBiBr6 while the negative phonon energy shifts induced by cubic anharmonicity has a significant influence on particle-like phonon propagation. Further, the contribution of the wave-like tunnelling to the total thermal conductivity surpasses that of the particle-like propagation above around 310 K, indicating the breakdown of the phonon gas picture conventionally used in the Peierls-Boltzmann Transport Equation. Importantly, further including four-phonon scatterings is required in achieving the dominance of wave-like tunnelling, as compared to the dominant particle-like propagation channel when considering only three-phonon scatterings. Our work highlights the importance of lattice anharmonicity and wave-like tunnelling of phonons in the thermal transport in lead-free halide double perovskites.
Digitally-defined ultrathin transparent wireless sensor network for room-scale imperceptible ambient intelligence
Authors: Jin Yunxia , Yu Mengxia , Nguyen Dat T. , Yang Xin , Li Zhipeng , Xiong Ze , Li Chenhui , Liu Yuxin , Kong Yong Lin , Ho John S. 
Published: February 2024

AbstractWireless and battery-free radio-frequency (RF) sensors can be used to create physical spaces that ambiently sense and respond to human activities. Making such sensors ultra-flexible and transparent is important to preserve the aesthetics of living environments, accommodate daily activities, and functionally integrate with objects. However, existing RF sensors are unable to simultaneously achieve high transparency, flexibility, and the electrical conductivity required for remote room-scale operation. Here, we report 4.5 µm RF tag sensors achieving transparency exceeding 90% that provide capabilities in room-scale ambient wireless sensing. We develop a laser-assisted water-based adhesion-reversion process to digitally realize computer-aided RF design at scale. By individually tagging multiple objects and regions of the human body, we demonstrate multiplexed wireless tracking of human-environment interactions and physiological signals at a range of up to 8 m. These radio-frequency identification sensors open opportunities for non-intrusive wireless sensing of daily living spaces for applications in health monitoring and elderly care.
TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans
Authors: Ishimoto Takahiro , Yamashita Reiya , Matsumoto Ruri , Matsumoto Satoshi , Matsuo Yusuke , Nakao Shunsuke , Masuo Yusuke , Suzuki Makoto , Kato Yukio 
Published: February 2024

AbstractOral administration of the food-derived antioxidant amino acid ergothioneine (ERGO) results in its efficient distribution in the brain and enhances cognitive function. However, effect of ERGO deficiency on cognitive impairment and the underlying mechanisms remain unknown. We revealed that cognitive function and hippocampal neurogenesis were lower in mice fed an ERGO-free diet than in those fed the control diet. Furthermore, ERGO supplementation to achieve the control diet ERGO levels reversed these effects and restored ERGO concentrations in the plasma and hippocampus. The ERGO-induced recovery of cognitive function and hippocampal neurogenesis was blocked by inhibiting the neurotrophic factor receptor tropomyosin receptor kinase B (TrkB), with a concomitant reduction in hippocampal phosphorylated TrkB, suggesting the involvement of TrkB in these events in mice. Phosphorylated TrkB was also detected in extracellular vesicles (EVs) derived from serum of volunteers who had been orally administered placebo or ERGO-containing tablets. Importantly, the ratio of serum EV-derived phosphorylated TrkB was significantly higher in the ERGO-treated group than in the placebo-treated group and was positively correlated with both serum ERGO concentrations and several cognitive domain scores from Cognitrax. Altogether, TrkB phosphorylation is involved in ERGO-induced cognitive enhancement in mice, and TrkB phosphorylation levels in serum EVs may quantitatively represent ERGO-induced cognitive enhancement in humans.
MYC targeting by OMO-103 in solid tumors: a phase 1 trial
Authors: Garralda Elena , Beaulieu Marie-Eve , Moreno Víctor , Casacuberta-Serra Sílvia , Martínez-Martín Sandra , Foradada Laia , Alonso Guzman , Massó-Vallés Daniel , López-Estévez Sergio , Jauset Toni , Corral de la Fuente Elena , Doger Bernard , Hernández Tatiana , Perez-Lopez Raquel , Arqués Oriol , Castillo Cano Virginia , Morales Josefa , Whitfield Jonathan R. , Niewel Manuela , Soucek Laura , Calvo Emiliano 
Published: February 2024

AbstractAmong the ‘most wanted’ targets in cancer therapy is the oncogene MYC, which coordinates key transcriptional programs in tumor development and maintenance. It has, however, long been considered undruggable. OMO-103 is a MYC inhibitor consisting of a 91-amino acid miniprotein. Here we present results from a phase 1 study of OMO-103 in advanced solid tumors, established to examine safety and tolerability as primary outcomes and pharmacokinetics, recommended phase 2 dose and preliminary signs of activity as secondary ones. A classical 3 + 3 design was used for dose escalation of weekly intravenous, single-agent OMO-103 administration in 21-day cycles, encompassing six dose levels (DLs). A total of 22 patients were enrolled, with treatment maintained until disease progression. The most common adverse events were grade 1 infusion-related reactions, occurring in ten patients. One dose-limiting toxicity occurred at DL5. Pharmacokinetics showed nonlinearity, with tissue saturation signs at DL5 and a terminal half-life in serum of 40 h. Of the 19 patients evaluable for response, 12 reached the predefined 9-week time point for assessment of drug antitumor activity, eight of those showing stable disease by computed tomography. One patient defined as stable disease by response evaluation criteria in solid tumors showed a 49% reduction in total tumor volume at best response. Transcriptomic analysis supported target engagement in tumor biopsies. In addition, we identified soluble factors that are potential pharmacodynamic and predictive response markers. Based on all these data, the recommended phase 2 dose was determined as DL5 (6.48 mg kg−1).ClinicalTrials.gov identifier: NCT04808362.
Preoperative CT and survival data for patients undergoing resection of colorectal liver metastases
Authors: Simpson Amber L. , Peoples Jacob , Creasy John M. , Fichtinger Gabor , Gangai Natalie , Keshavamurthy Krishna N. , Lasso Andras , Shia Jinru , D’Angelica Michael I. , Do Richard K. G. 
Published: February 2024

AbstractThe liver is a common site for the development of metastases in colorectal cancer. Treatment selection for patients with colorectal liver metastases (CRLM) is difficult; although hepatic resection will cure a minority of CRLM patients, recurrence is common. Reliable preoperative prediction of recurrence could therefore be a valuable tool for physicians in selecting the best candidates for hepatic resection in the treatment of CRLM. It has been hypothesized that evidence for recurrence could be found via quantitative image analysis on preoperative CT imaging of the future liver remnant before resection. To investigate this hypothesis, we have collected preoperative hepatic CT scans, clinicopathologic data, and recurrence/survival data, from a large, single-institution series of patients (n = 197) who underwent hepatic resection of CRLM. For each patient, we also created segmentations of the liver, vessels, tumors, and future liver remnant. The largest of its kind, this dataset is a resource that may aid in the development of quantitative imaging biomarkers and machine learning models for the prediction of post-resection hepatic recurrence of CRLM.
Homologous Recombination Deficiency Unrelated to Platinum and PARP Inhibitor Response in Cell Line Libraries
Authors: Takamatsu Shiro , Murakami Kosuke , Matsumura Noriomi 
Published: February 2024

AbstractWhile large publicly available cancer cell line databases are invaluable for preclinical drug discovery and biomarker development, the association between homologous recombination deficiency (HRD) and drug sensitivity in these resources remains unclear. In this study, we comprehensively analyzed molecular profiles and drug screening data from the Cancer Cell Line Encyclopedia. Unexpectedly, gene alterations in BRCA1/2 or homologous recombination-related genes, HRD scores, or mutational signature 3 were not positively correlated with sensitivity to platinum agents or PARP inhibitors. Rather, higher HRD scores and mutational signature 3 were significantly associated with resistance to these agents in multiple assays. These findings were consistent when analyzing exclusively breast and ovarian cancer cell lines and when using data from the COSMIC Cell Line Project. Collectively, the existing data from established cancer cell lines do not reflect the expected association between HRD status and drug response to platinum agents and PARP inhibitors in clinical tumors. This discrepancy may extend to other tumor characteristics, highlighting the importance of recognizing potential limitations in cell line data for researchers.
Embryonic ethanol exposure and optogenetic activation of hypocretin neurons stimulate similar behaviors early in life associated with later alcohol consumption
Authors: Collier Adam D. , Yasmin Nushrat , Karatayev Olga , Abdulai Abdul R. , Yu Boyi , Fam Milisia , Campbell Samantha , Leibowitz Sarah F. 
Published: February 2024

AbstractThe initiation of alcohol use early in life is one of the strongest predictors of developing a future alcohol use disorder. Clinical studies have identified specific behaviors during early childhood that predict an increased risk for excess alcohol consumption later in life. These behaviors, including increased hyperactivity, anxiety, novelty-seeking, exploratory behavior, impulsivity, and alcohol-seeking, are similarly stimulated in children and adolescent offspring of mothers who drink alcohol during pregnancy. Here we tested larval zebrafish in addition to young pre-weanling rats and found this repertoire of early behaviors along with the overconsumption of alcohol during adolescence to be increased by embryonic ethanol exposure. With hypocretin/orexin (Hcrt) neurons known to be stimulated by ethanol and involved in mediating these alcohol-related behaviors, we tested their function in larval zebrafish and found optogenetic activation of Hcrt neurons to stimulate these same early alcohol-related behaviors and later alcohol intake, suggesting that these neurons have an important role in producing these behaviors. Together, these results show zebrafish to be an especially useful animal model for investigating the diverse neuronal systems mediating behavioral changes at young ages that are produced by embryonic ethanol exposure and predict an increased risk for developing alcohol use disorder.
Air pollution seasons in urban moderate climate areas through big data analytics
Authors: Zareba Mateusz , Weglinska Elzbieta , Danek Tomasz 
Published: February 2024

AbstractHigh particulate matter (PM) concentrations have a negative impact on the overall quality of life and health. The annual trends of PM can vary greatly depending on factors such as a country’s energy mix, development level, and climatic zone. In this study, we aimed to understand the annual cycle of PM concentrations in a moderate climate zone using a dense grid of low-cost sensors located in central Europe (Krakow). Over one million unique records of PM, temperature, humidity, pressure and wind speed observations were analyzed to gain a detailed, high-resolution understanding of yearly fluctuations. The comprehensive big-data workflow was presented with the statistical analysis of the meteorological factors. A big data-driven approach revealed the existence of two main PM seasons (warm and cold) in Europe’s moderate climate zone, which do not correspond directly with the traditional four main seasons (Autumn, Winter, Spring, and Summer) with two side periods (early spring and early winter). Our findings also highlighted the importance of high-resolution time and space data for sustainable spatial planning. The observations allowed for distinguishing whether the source of air pollution is related to coal burning for heating in cold period or to agricultural lands burning during the warm period.
Emotion regulation shows an age- and sex-specific moderating effect on the relationship between chronic stress and cognitive performance
Authors: Novotný Jan S. , Srt Luka , Stokin Gorazd B. 
Published: February 2024

AbstractDespite the extensive knowledge about the effects of chronic stress on cognition, the underlying mechanisms remain unclear. We conducted a cross-sectional moderation analysis on a population-based sample of 596 adults to examine the age- and sex-specific role of emotion regulation (ER) in the relationship between chronic stress and cognitive performance using validated self-report questionnaires. While women showed no direct or moderated relationship between stress and cognition, men displayed a distinct age-related pattern where stress was negatively associated with poorer cognitive performance at older ages, and the onset of this relationship was detected earlier in men with ER problems. These results showed that suppression of emotions and lack of executive control of ER amplify the negative consequences of chronic stress and suggest that there are sex-specific differences in the decline of ability to cope with long-term exposure to stressors.
Correlation between peri-implant bone mineral density and primary implant stability based on artificial intelligence classification
Authors: Xiao Yanjun , Lv Lingfeng , Xu Zonghe , Zhou Lin , Lin Yanjun , Lin Yue , Guo Jianbin , Chen Jiang , Ou Yanjing , Lin Lin , Wu Dong 
Published: February 2024

AbstractCurrently, the classification of bone mineral density (BMD) in many research studies remains rather broad, often neglecting localized changes in BMD. This study aims to explore the correlation between peri-implant BMD and primary implant stability using a new artificial intelligence (AI)-based BMD grading system. 49 patients who received dental implant treatment at the Affiliated Hospital of Stomatology of Fujian Medical University were included. Recorded the implant stability quotient (ISQ) after implantation and the insertion torque value (ITV). A new AI-based BMD grading system was used to obtain the distribution of BMD in implant site, and the bone mineral density coefficients (BMDC) of the coronal, middle, apical, and total of the 1 mm site outside the implant were calculated by model overlap and image overlap technology. Our objective was to investigate the relationship between primary implant stability and BMDC values obtained from the new AI-based BMD grading system. There was a significant positive correlation between BMDC and ISQ value in the coronal, middle, and total of the implant (P < 0.05). However, there was no significant correlation between BMDC and ISQ values in the apical (P > 0.05). Furthermore, BMDC was notably higher at implant sites with greater ITV (P < 0.05). BMDC calculated from the new AI-based BMD grading system could more accurately present the BMD distribution in the intended implant site, thereby providing a dependable benchmark for predicting primary implant stability.
Enhanced Aquila optimizer based on tent chaotic mapping and new rules
Authors: Fu Youfa , Liu Dan , Fu Shengwei , Chen Jiadui , He Ling 
Published: February 2024

AbstractMetaheuristic algorithms, widely applied across various domains due to their simplicity and strong optimization capabilities, play a crucial role in problem-solving. While the Aquila Optimizer is recognized for its effectiveness, it often exhibits slow convergence rates and susceptibility to local optima in certain scenarios. To address these concerns, this paper introduces an enhanced version, termed Tent-enhanced Aquila Optimizer (TEAO). TEAO incorporates the Tent chaotic map to initialize the Aquila population, promoting a more uniform distribution within the solution space. To balance exploration and exploitation, novel formulas are proposed, accelerating convergence while ensuring precision. The effectiveness of the TEAO algorithm is validated through a comprehensive comparison with 14 state-of-the-art algorithms using 23 classical benchmark test functions. Additionally, to assess the practical feasibility of the approach, TEAO is applied to six constrained engineering problems and benchmarked against the performance of the same 14 algorithms. All experimental results consistently demonstrate that TEAO outperforms other advanced algorithms in terms of solution quality and stability, establishing it as a more competitive choice for optimization tasks.