bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and imaging features of women with polygenic partial lipodystrophy: a case series
Authors: Loh Wann Jia , Yaligar Jadegoud , Hooper Amanda J. , Sadananthan Suresh Anand , Kway Yeshe , Lim Su Chi , Watts Gerald.F. , Velan Sambasivam Sendhil , Leow Melvin Khee Shing , Khoo Joan
Published: February 2024

Background

Familial partial lipodystrophy (FPLD) is an inherited disorder of white adipose tissue that causes premature cardiometabolic disease. There is no clear diagnostic criteria for FPLD, and this may explain the under-detection of this condition.

Aim

This pilot study aimed to describe the clinical features of women with FPLD and to explore the value of adipose tissue measurements that could be useful in diagnosis.

Methods

In 8 women with FPLD and 4 controls, skinfold measurements, DXA and whole-body MRI were undertaken.

Results

Whole genome sequencing was negative for monogenic metabolic causes, but polygenic scores for partial lipodystrophy were elevated in keeping with FPLD type 1. The mean age of diagnosis of DM was 31 years in the FPLD group. Compared with controls, the FPLD group had increased HOMA-IR (10.3 vs 2.9, p = 0.028) and lower mean thigh skinfold thickness (19.5 mm vs 48.2 mm, p = 0.008). The FPLD group had lower percentage of leg fat and an increased ratio of trunk to leg fat percentage on DXA. By MRI, the FPLD group had decreased subcutaneous adipose tissue (SAT) volume in the femoral and calf regions (p < 0.01); abdominal SAT, visceral adipose tissue, and femoral and calf muscle volumes were not different from controls.

Conclusion

Women with FPLD1 in Singapore have significant loss of adipose but not muscle tissue in lower limbs and have early onset of diabetes. Reduced thigh skinfold, and increased ratio of trunk to leg fat percentage on DXA are potentially clinically useful markers to identify FPLD1.
Genome-wide association study implicates the role of TBXAS1 in the pathogenesis of depressive symptoms among the Korean population
Authors: Park Kyungtaek , Do Ah Ra , Chung Yuree , Kim Min Ji , Rhee Sang Jin , Yoon Dae Hyun , Choi Seung Ho , Cho Sung Joon , Kim Han-Na , Ahn Yong Min , Won Sungho
Published: February 2024

Although depression is an emerging disorder affecting many people worldwide, most genetic studies have been performed in European descent populations. Herein, a genome-wide association study (GWAS) was conducted in Korean population to elucidate the genomic loci associated with depressive symptoms. Two independent cohorts were used as discovery datasets, which consisted of 6474 (1484 cases and 4990 controls) and 1654 (557 cases and 1097 controls) Korean participants, respectively. The participants were divided into case and control groups based on the Beck Depression Inventory (BDI). Meta-analysis using the two cohorts revealed that rs6945590 was significantly associated with the risk of depressive symptoms [P = 2.83 × 10−8; odds ratio (OR) = 1.23; 95% confidence interval (CI): 1.15–1.33]. This association was validated in other independent cohorts which were another Korean cohort (258 cases and 1757 controls) and the East Asian study of the Psychiatric Genomics Consortium (PGC) (12,455 cases and 85,548 controls). The predicted expression levels of thromboxane A synthase 1 gene (TBXAS1), which encodes the enzyme thromboxane A synthase 1 and participates in the arachidonic acid (AA) cascade, was significantly decreased in the whole blood tissues of the participants with depressive symptoms. Furthermore, Mendelian randomization (MR) analysis showed a causal association between TBXAS1 expression and the risk of depressive symptoms. In conclusion, as the number of risk alleles (A) of rs6945590 increased, TBXAS1 expression decreased, which subsequently caused an increase in the risk of depressive symptoms.
Prefrontal cortical dopamine deficit may cause impaired glucose metabolism in schizophrenia
Authors: Wu Qiongqiong , Long Yujun , Peng Xingjie , Song Chuhan , Xiao Jingmei , Wang Xiaoyi , Liu Furu , Xie Peng , Yang Jinqing , Shi Zhe , Hu Zhonghua , McCaig Colin , St Clair David , Lang Bing , Wu Renrong
Published: February 2024

The brain neurotramsmitter dopamine may play an important role in modulating systemic glucose homeostasis. In seven hundred and four drug- naïve patients with first-episode schizophrenia, we provide robust evidence of positive associations between negative symptoms of schizophrenia and high fasting blood glucose. We then show that glucose metabolism and negative symptoms are improved when intermittent theta burst stimulation (iTBS) on prefrontal cortex (PFC) is performed in patients with predominantly negative symptoms of schizophrenia. These findings led us to hypothesize that the prefrontal cortical dopamine deficit, which is known to be associated with negative symptoms, may be responsible for abnormal glucose metabolism in schizophrenia. To explore this, we optogenetically and chemogenetically inhibited the ventral tegmental area (VTA)-medial prefrontal cortex (mPFC) dopamine projection in mice and found both procedures caused glucose intolerance. Moreover, microinjection of dopamine two receptor (D2R) neuron antagonists into mPFC in mice significantly impaired glucose tolerance. Finally, a transgenic mouse model of psychosis named Disc1tr exhibited depressive-like symptoms, impaired glucose homeostasis, and compared to wild type littermates reduced D2R expression in prefrontal cortex.
ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models
Authors: Hu Rui , Chen Xiangyi , Su Qiang , Wang Zhaoyue , Wang Xushu , Gong Mengting , Xu Minglu , Le Rongrong , Gao Yawei , Dai Peng , Zhang Zhen-Ning , Shao Li , Li Weida
Published: February 2024

Pancreatic β-cell failure by WFS1 deficiency is manifested in individuals with wolfram syndrome (WS). The lack of a suitable human model in WS has impeded progress in the development of new treatments. Here, human pluripotent stem cell derived pancreatic islets (SC-islets) harboring WFS1 deficiency and mouse model of β cell specific Wfs1 knockout were applied to model β-cell failure in WS. We charted a high-resolution roadmap with single-cell RNA-seq (scRNA-seq) to investigate pathogenesis for WS β-cell failure, revealing two distinct cellular fates along pseudotime trajectory: maturation and stress branches. WFS1 deficiency disrupted β-cell fate trajectory toward maturation and directed it towards stress trajectory, ultimately leading to β-cell failure. Notably, further investigation of the stress trajectory identified activated integrated stress response (ISR) as a crucial mechanism underlying WS β-cell failure, characterized by aberrant eIF2 signaling in WFS1-deficient SC-islets, along with elevated expression of genes in regulating stress granule formation. Significantly, we demonstrated that ISRIB, an ISR inhibitor, efficiently reversed β-cell failure in WFS1-deficient SC-islets. We further validated therapeutic efficacy in vivo with β-cell specific Wfs1 knockout mice. Altogether, our study provides novel insights into WS pathogenesis and offers a strategy targeting ISR to treat WS diabetes.
Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma
Authors: Fang Xue-Liang , Li Qing-Jie , Lin Jia-Yi , Huang Cheng-Long , Huang Sheng-Yan , Tan Xi-Rong , He Shi-Wei , Zhu Xun-Hua , Li Jun-Yan , Gong Sha , Qiao Han , Li Ying-Qin , Liu Na , Ma Jun , Zhao Yin , Tang Ling-Long
Published: February 2024

Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients’ survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.
GITRL impairs hepatocyte repopulation by liver progenitor cells to aggravate inflammation and fibrosis by GITR+CD8+ T lymphocytes in CDE Mice
Authors: Li Li , He Yu , Liu Kai , Liu Lin , Shan Shan , Liu Helin , Ren Jiangbo , Sun Shujie , Wang Min , Jia Jidong , Wang Ping
Published: February 2024

As an alternative pathway for liver regeneration, liver progenitor cells and their derived ductular reaction cells increase during the progression of many chronic liver diseases. However, the mechanism underlying their hepatocyte repopulation after liver injury remains unknown. Here, we conducted progenitor cell lineage tracing in mice and found that fewer than 2% of hepatocytes were derived from liver progenitor cells after 9 weeks of injury with a choline-deficient diet supplemented with ethionine (CDE), and this percentage increased approximately three-fold after 3 weeks of recovery. We also found that the proportion of liver progenitor cells double positive for the ligand of glucocorticoid-induced tumour necrosis factor receptor (GITRL, also called Tnfsf18) and SRY-related HMG box transcription 9 (Sox9) among nonparenchymal cells increased time-dependently upon CDE injury and reduced after recovery. When GITRL was conditionally knocked out from hepatic progenitor cells, its expression in nonparenchymal cells was downregulated by approximately fifty percent, and hepatocyte repopulation increased by approximately three folds. Simultaneously, conditional knockout of GITRL reduced the proportion of liver-infiltrating CD8+ T lymphocytes and glucocorticoid-induced tumour necrosis factor receptor (GITR)-positive CD8+ T lymphocytes. Mechanistically, GITRL stimulated cell proliferation but suppressed the differentiation of liver progenitor organoids into hepatocytes, and CD8+ T cells further reduced their hepatocyte differentiation by downregulating the Wnt/β-catenin pathway. Therefore, GITRL expressed by liver progenitor cells impairs hepatocyte differentiation, thus hindering progenitor cell-mediated liver regeneration.
IL-8 activates fibroblasts to promote the invasion of HNSCC cells via STAT3-MMP1
Authors: Chen Yu , Huang Li , Gan Rui-Huan , Yuan Shuo , Lan Ting , Zheng Dali , Lu You-Guang
Published: February 2024

Matrix metalloproteinase-1 (MMP1) has an aberrant expression relevant to various behaviors of cancers. As dominant components of the tumor stroma, fibroblasts constitute an important source of Matrix metalloproteinase (MMPs) including mainly MMP1. The impacts of MMP1 derived from fibroblasts in tumor microenvironment, however, is not well defined. In this study, we demonstrated a part of crosstalk between fibroblasts and cancer cells that enhanced the invasiveness of cancer cells, IL8-induced activation of STAT3 signaling pathway as a key promoter to elevated MMP1 level in fibroblasts that supports the migration and invasion of head and neck squamous cell carcinoma (HNSCC) cells by extracellular matrix degradation. Importantly, once exposed to the inhibitor of STAT3 phosphorylation (TPCA-1), the enhanced induction of HNSCC cells invasion triggered by fibroblasts was significantly impaired.
The impact of reproductive factors on the metabolic profile of females from menarche to menopause
Authors: Clayton Gemma L. , Borges Maria Carolina , Lawlor Deborah A.
Published: February 2024

We explore the relation between age at menarche, parity and age at natural menopause with 249 metabolic traits in over 65,000 UK Biobank women using multivariable regression, Mendelian randomization and negative control (parity only). Older age of menarche is related to a less atherogenic metabolic profile in multivariable regression and Mendelian randomization, which is largely attenuated when accounting for adult body mass index. In multivariable regression, higher parity relates to more particles and lipids in VLDL, which are not observed in male negative controls. In multivariable regression and Mendelian randomization, older age at natural menopause is related to lower concentrations of inflammation markers, but we observe inconsistent results for LDL-related traits due to chronological age-specific effects. For example, older age at menopause is related to lower LDL-cholesterol in younger women but slightly higher in older women. Our findings support a role of reproductive traits on later life metabolic profile and provide insights into identifying novel markers for the prevention of adverse cardiometabolic outcomes in women.
Implicit racial biases are lower in more populous more diverse and less segregated US cities
Authors: Stier Andrew J. , Sajjadi Sina , Karimi Fariba , Bettencourt Luís M. A. , Berman Marc G.
Published: February 2024

Implicit biases - differential attitudes towards members of distinct groups - are pervasive in human societies and create inequities across many aspects of life. Recent research has revealed that implicit biases are generally driven by social contexts, but not whether they are systematically influenced by the ways that humans self-organize in cities. We leverage complex system modeling in the framework of urban scaling theory to predict differences in these biases between cities. Our model links spatial scales from city-wide infrastructure to individual psychology to predict that cities that are more populous, more diverse, and less segregated are less biased. We find empirical support for these predictions in U.S. cities with Implicit Association Test data spanning a decade from 2.7 million individuals and U.S. Census demographic data. Additionally, we find that changes in cities’ social environments precede changes in implicit biases at short time-scales, but this relationship is bi-directional at longer time-scales. We conclude that the social organization of cities may influence the strength of these biases.
Heavy-to-light electron transition enabling real-time spectra detection of charged particles by a biocompatible semiconductor
Authors: Zhao Dou , Gao Ruiling , Cheng Wei , Wen Mengyao , Zhang Xinlei , Yokota Tomoyuki , Sellin Paul , Yang Shengyuan A. , Shang Li , Zhou Chongjian , Someya Takao , Jie Wanqi , Xu Yadong
Published: February 2024

The current challenge of wearable/implantable personal dosimeters for medical diagnosis and radiotherapy applications is lack of suitable detector materials possessing both excellent detection performance and biocompatibility. Here, we report a solution-grown biocompatible organic single crystalline semiconductor (OSCS), 4-Hydroxyphenylacetic acid (4HPA), achieving real-time spectral detection of charged particles with single-particle sensitivity. Along in-plane direction, two-dimensional anisotropic 4HPA exhibits a large electron drift velocity of 5 × 105 cm s−1 at “radiation-mode” while maintaining a high resistivity of (1.28 ± 0.003) × 1012 Ω·cm at “dark-mode” due to influence of dense π-π overlaps and high-energy L1 level. Therefore, 4HPA detectors exhibit the record spectra detection of charged particles among their organic counterparts, with energy resolution of 36%, (μt)e of (4.91 ± 0.07) × 10−5 cm2 V−1, and detection time down to 3 ms. These detectors also show high X-ray detection sensitivity of 16,612 μC Gyabs−1 cm−3, detection of limit of 20 nGyair s−1, and long-term stability after 690 Gyair irradiation.
Learning nonequilibrium statistical mechanics and dynamical phase transitions
Authors: Tang Ying , Liu Jing , Zhang Jiang , Zhang Pan
Published: February 2024

Nonequilibrium statistical mechanics exhibit a variety of complex phenomena far from equilibrium. It inherits challenges of equilibrium, including accurately describing the joint distribution of a large number of configurations, and also poses new challenges as the distribution evolves over time. Characterizing dynamical phase transitions as an emergent behavior further requires tracking nonequilibrium systems under a control parameter. While a number of methods have been proposed, such as tensor networks for one-dimensional lattices, we lack a method for arbitrary time beyond the steady state and for higher dimensions. Here, we develop a general computational framework to study the time evolution of nonequilibrium systems in statistical mechanics by leveraging variational autoregressive networks, which offer an efficient computation on the dynamical partition function, a central quantity for discovering the phase transition. We apply the approach to prototype models of nonequilibrium statistical mechanics, including the kinetically constrained models of structural glasses up to three dimensions. The approach uncovers the active-inactive phase transition of spin flips, the dynamical phase diagram, as well as new scaling relations. The result highlights the potential of machine learning dynamical phase transitions in nonequilibrium systems.
Photo-thermal coupling to enhance CO2 hydrogenation toward CH4 over Ru/MnO/Mn3O4
Authors: Zhai Jianxin , Xia Zhanghui , Zhou Baowen , Wu Haihong , Xue Teng , Chen Xiao , Jiao Jiapeng , Jia Shuaiqiang , He Mingyuan , Han Buxing
Published: February 2024

Upcycling of CO2 into fuels by virtually unlimited solar energy provides an ultimate solution for addressing the substantial challenges of energy crisis and climate change. In this work, we report an efficient nanostructured Ru/MnOx catalyst composed of well-defined Ru/MnO/Mn3O4 for photo-thermal catalytic CO2 hydrogenation to CH4, which is the result of a combination of external heating and irradiation. Remarkably, under relatively mild conditions of 200 °C, a considerable CH4 production rate of 166.7 mmol g−1 h−1 was achieved with a superior selectivity of 99.5% at CO2 conversion of 66.8%. The correlative spectroscopic and theoretical investigations suggest that the yield of CH4 is enhanced by coordinating photon energy with thermal energy to reduce the activation energy of reaction and promote formation of key intermediate COOH* species over the catalyst. This work opens up a new strategy for CO2 hydrogenation toward CH4.
Multicompartmental coacervate-based protocell by spontaneous droplet evaporation
Authors: Qi Cheng , Ma Xudong , Zeng Qi , Huang Zhangwei , Zhang Shanshan , Deng Xiaokang , Kong Tiantian , Liu Zhou
Published: February 2024

Hierarchical compartmentalization, a hallmark of both primitive and modern cells, enables the concentration and isolation of biomolecules, and facilitates spatial organization of biochemical reactions. Coacervate-based compartments can sequester and recruit a large variety of molecules, making it an attractive protocell model. In this work, we report the spontaneous formation of core-shell cell-sized coacervate-based compartments driven by spontaneous evaporation of a sessile droplet on a thin-oil-coated substrate. Our analysis reveals that such far-from-equilibrium architectures arise from multiple, coupled segregative and associative liquid-liquid phase separation, and are stabilized by stagnation points within the evaporating droplet. The formation of stagnation points results from convective capillary flows induced by the maximum evaporation rate at the liquid-liquid-air contact line. This work provides valuable insights into the spontaneous formation and maintenance of hierarchical compartments under non-equilibrium conditions, offering a glimpse into the real-life scenario.
Heat shock protein gp96 drives natural killer cell maturation and anti-tumor immunity by counteracting Trim28 to stabilize Eomes
Authors: Xu Yuxiu , Li Xin , Cheng Fang , Zhao Bao , Fang Min , Li Zihai , Meng Songdong
Published: February 2024

The maturation process of natural killer (NK) cells, which is regulated by multiple transcription factors, determines their functionality, but few checkpoints specifically targeting this process have been thoroughly studied. Here we show that NK-specific deficiency of glucose-regulated protein 94 (gp96) leads to decreased maturation of NK cells in mice. These gp96-deficient NK cells exhibit undermined activation, cytotoxicity and IFN-γ production upon stimulation, as well as weakened responses to IL-15 for NK cell maturation, in vitro. In vivo, NK-specific gp96-deficient mice show increased tumor growth. Mechanistically, we identify Eomes as the downstream transcription factor, with gp96 binding to Trim28 to prevent Trim28-mediated ubiquitination and degradation of Eomes. Our study thus suggests the gp96-Trim28-Eomes axis to be an important regulator for NK cell maturation and cancer surveillance in mice.
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

Accurate 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

Shape-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

The 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

Understanding 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

Wireless 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

Oral 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

Among 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

The 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

While 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

The 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

High 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

Despite 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

Currently, 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

Metaheuristic 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.
Classification of human walking context using a single-point accelerometer
Authors: Baroudi Loubna , Barton Kira , Cain Stephen M. , Shorter K. Alex
Published: February 2024

Real-world walking data offers rich insights into a person’s mobility. Yet, daily life variations can alter these patterns, making the data challenging to interpret. As such, it is essential to integrate context for the extraction of meaningful information from real-world movement data. In this work, we leveraged the relationship between the characteristics of a walking bout and context to build a classification algorithm to distinguish between indoor and outdoor walks. We used data from 20 participants wearing an accelerometer on the thigh over a week. Their walking bouts were isolated and labeled using GPS and self-reporting data. We trained and validated two machine learning models, random forest and ensemble Support Vector Machine, using a leave-one-participant-out validation scheme on 15 subjects. The 5 remaining subjects were used as a testing set to choose a final model. The chosen model achieved an accuracy of 0.941, an F1-score of 0.963, and an AUROC of 0.931. This validated model was then used to label the walks from a different dataset with 15 participants wearing the same accelerometer. Finally, we characterized the differences between indoor and outdoor walks using the ensemble of the data. We found that participants walked significantly faster, longer, and more continuously when walking outdoors compared to indoors. These results demonstrate how movement data alone can be used to obtain accurate information on important contextual factors. These factors can then be leveraged to enhance our understanding and interpretation of real-world movement data, providing deeper insights into a person’s health.
The temperature sensitivity of motor units in rat soleus
Authors: Malak Bartosz , Celichowski Jan , Drzymała-Celichowska Hanna
Published: February 2024

Temperature has a significant impact on the performance of the neuromuscular system and motor control processes. The smallest functional components of these systems are motor units (MUs), which may differ significantly between different muscles. The influence of temperature on the contractile properties of slow-twitch (S) MUs from soleus (SOL) muscles in rats was investigated under hypothermia (25 °C), normothermia (37 °C), and hyperthermia (41 °C). Hypothermia prolonged the twitch time parameters, decreased the rate of force development, increased the twitch-to-tetanus ratio, enhanced twitch force, and abolished post-tetanic depression. In contrast, hyperthermia did not alter twitch time parameters. Moreover, there was no effect on force despite the noted increase in post-tetanic depression and the twitch-to-tetanus ratio. Therefore, hypothermia induced more profound changes in S MUs compared with hyperthermia. The temperature effects in SOL MUs were compared to the effects previously reported for S MUs in the medial gastrocnemius (MG). The major differences between the S MUs of both muscles were the effects of temperature on twitch force, post-tetanic force modulation, twitch-to-tetanus ratio, and the slope of the force-frequency curve under hypothermia. Hyperthermia shortened twitch time parameters solely in the MG. In contrast, post-tetanic depression, twitch-to-tetanus ratio, and the slope of the force-frequency curve were influenced by hyperthermia only in SOL MUs. The different temperature effects of S MUs probably corresponded to differences in muscle architecture and their diverse functional tasks and enzyme activity. In summary, S MUs in SOL are more thermal-sensitive than their counterparts in MG.