bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive role of ctDNA in esophageal squamous cell carcinoma receiving definitive chemoradiotherapy combined with toripalimab
Authors: Chen Baoqing , Liu Shiliang , Zhu Yujia , Wang Ruixi , Cheng Xingyuan , Chen Biqi , Dragomir Mihnea P. , Zhang Yaru , Hu Yonghong , Liu Mengzhong , Li Qiaoqiao , Yang Hong , Xi Mian 
Published: March 2024

AbstractThe combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and quality of life. The exploratory analyses of EC-CRT-001 include exploring the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) in predicting the response and survival. In total, 118 blood and 35 tissue samples from 42 enrolled patients were included in the analyses. We found that ctDNA-negative patients achieved a higher cCR compared to those with detectable ctDNA during CRT (83%, 19/23 vs. 39%, 7/18; p = 0.008) or post-CRT (78%, 21/27 vs. 30%, 3/10; p = 0.017). Patients with detectable ctDNA during CRT had shorter PFS (p = 0.014). Similarly, patients with post-CRT detectable ctDNA had a significantly shorter PFS (p = 0.012) and worse OS (p = 0.004). Moreover, patients with high bTMB levels during CRT had prolonged OS (p = 0.027). In conclusion, ctDNA and bTMB have the potential to predict treatment efficacy and survival in ESCC treated with CRT and immunotherapy.
Modulation-free laser stabilization technique using integrated cavity-coupled Mach-Zehnder interferometer
Authors: Idjadi Mohamad Hossein , Kim Kwangwoong , Fontaine Nicolas K. 
Published: March 2024

AbstractStable lasers play a significant role in precision optical systems where an electro-optic laser frequency stabilization system, such as the Pound-Drever-Hall technique, measures laser frequency and actively stabilizes it by comparing it to a frequency reference. Despite their excellent performance, there has been a trade-off between complexity, scalability, and noise measurement sensitivity. Here, we propose and experimentally demonstrate a modulation-free laser stabilization method using an integrated cavity-coupled Mach-Zehnder interferometer as a frequency noise discriminator. The proposed architecture maintains the sensitivity of the Pound-Drever-Hall architecture without the need for any modulation. This significantly simplifies the architecture and makes miniaturization into an integrated photonic platform easier. The implemented chip suppresses the frequency noise of a semiconductor laser by 4 orders-of-magnitude using an on-chip silicon microresonator with a quality factor of 2.5 × 106. The implemented passive photonic chip occupies an area of 0.456 mm2 and is integrated on AIM Photonics 100 nm silicon-on-insulator process.
synNotch-programmed iPSC-derived NK cells usurp TIGIT and CD73 activities for glioblastoma therapy
Authors: Lupo Kyle B. , Yao Xue , Borde Shambhavi , Wang Jiao , Torregrosa-Allen Sandra , Elzey Bennett D. , Utturkar Sagar , Lanman Nadia A. , McIntosh MacKenzie , Matosevic Sandro 
Published: March 2024

AbstractSevere heterogeneity within glioblastoma has spurred the notion that disrupting the interplay between multiple elements on immunosuppression is at the core of meaningful anti-tumor responses. T cell immunoreceptor with Ig and ITIM domains (TIGIT) and its glioblastoma-associated antigen, CD155, form a highly immunosuppressive axis in glioblastoma and other solid tumors, yet targeting of TIGIT, a functionally heterogeneous receptor on tumor-infiltrating immune cells, has largely been ineffective as monotherapy, suggesting that disruption of its inhibitory network might be necessary for measurable responses. It is within this context that we show that the usurpation of the TIGIT − CD155 axis via engineered synNotch-mediated activation of induced pluripotent stem cell-derived natural killer (NK) cells promotes transcription factor-mediated activation of a downstream signaling cascade that results in the controlled, localized blockade of CD73 to disrupt purinergic activity otherwise resulting in the production and accumulation of immunosuppressive extracellular adenosine. Such “decoy” receptor engages CD155 binding to TIGIT, but tilts inhibitory TIGIT/CD155 interactions toward activation via downstream synNotch signaling. Usurping activities of TIGIT and CD73 promotes the function of adoptively transferred NK cells into intracranial patient-derived models of glioblastoma and enhances their natural cytolytic functions against this tumor to result in complete tumor eradication. In addition, targeting both receptors, in turn, reprograms the glioblastoma microenvironment via the recruitment of T cells and the downregulation of M2 macrophages. This study demonstrates that TIGIT/CD155 and CD73 are targetable receptor partners in glioblastoma. Our data show that synNotch-engineered pluripotent stem cell-derived NK cells are not only effective mediators of anti-glioblastoma responses within the setting of CD73 and TIGIT/CD155 co-targeting, but represent a powerful allogeneic treatment option for this tumor.
Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2–SP1–SAT1 axis
Authors: Murthy Divya , Attri Kuldeep S. , Shukla Surendra K. , Thakur Ravi , Chaika Nina V. , He Chunbo , Wang Dezhen , Jha Kanupriya , Dasgupta Aneesha , King Ryan J. , Mulder Scott E. , Souchek Joshua , Gebregiworgis Teklab , Rai Vikant , Patel Rohit , Hu Tuo , Rana Sandeep , Kollala Sai Sundeep , Pacheco Camila , Grandgenett Paul M. , Yu Fang , Kumar Vikas , Lazenby Audrey J. , Black Adrian R. , Ulhannan Susanna , Jain Ajay , Edil Barish H. , Klinkebiel David L. , Powers Robert , Natarajan Amarnath , Hollingsworth Michael A. , Mehla Kamiya , Ly Quan , Chaudhary Sarika , Hwang Rosa F. , Wellen Kathryn E. , Singh Pankaj K. 
Published: March 2024

AbstractThe ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment. Comparative H3K27ac ChIP–seq and RNA–seq analyses revealed alterations in polyamine homeostasis through regulation of SAT1 gene expression and enrichment of the SP1-responsive signature. We identified acetate/ACSS2-mediated acetylation of SP1 at the lysine 19 residue that increased SP1 protein stability and transcriptional activity. Genetic or pharmacologic inhibition of the ACSS2–SP1–SAT1 axis diminished the tumour burden in mouse models. These results reveal that the metabolic flexibility imparted by the stroma-derived acetate enabled cancer cell survival under acidosis via the ACSS2–SP1–SAT1 axis.
A charge-dependent long-ranged force drives tailored assembly of matter in solution
Authors: Wang Sida , Walker-Gibbons Rowan , Watkins Bethany , Flynn Melissa , Krishnan Madhavi 
Published: March 2024

AbstractThe interaction between charged objects in solution is generally expected to recapitulate two central principles of electromagnetics: (1) like-charged objects repel, and (2) they do so regardless of the sign of their electrical charge. Here we demonstrate experimentally that the solvent plays a hitherto unforeseen but crucial role in interparticle interactions, and importantly, that interactions in the fluid phase can break charge-reversal symmetry. We show that in aqueous solution, negatively charged particles can attract at long range while positively charged particles repel. In solvents that exhibit an inversion of the net molecular dipole at an interface, such as alcohols, we find that the converse can be true: positively charged particles may attract whereas negatives repel. The observations hold across a wide variety of surface chemistries: from inorganic silica and polymeric particles to polyelectrolyte- and polypeptide-coated surfaces in aqueous solution. A theory of interparticle interactions that invokes solvent structuring at an interface captures the observations. Our study establishes a nanoscopic interfacial mechanism by which solvent molecules may give rise to a strong and long-ranged force in solution, with immediate ramifications for a range of particulate and molecular processes across length scales such as self-assembly, gelation and crystallization, biomolecular condensation, coacervation, and phase segregation.
Cavity-mediated long-range interactions in levitated optomechanics
Authors: Vijayan Jayadev , Piotrowski Johannes , Gonzalez-Ballestero Carlos , Weber Kevin , Romero-Isart Oriol , Novotny Lukas 
Published: March 2024

AbstractThe ability to engineer cavity-mediated interactions has emerged as a powerful tool for the generation of non-local correlations and the investigation of non-equilibrium phenomena in many-body systems. Levitated optomechanical systems have recently entered the multiparticle regime, which promises the use of arrays of strongly coupled massive oscillators to explore complex interacting systems and sensing. Here we demonstrate programmable cavity-mediated interactions between nanoparticles in vacuum by combining advances in multiparticle optical levitation and cavity-based quantum control. The interaction is mediated by photons scattered by spatially separated particles in a cavity, resulting in strong coupling that is long-range in nature. We investigate the scaling of the interaction strength with cavity detuning and interparticle separation and demonstrate the tunability of interactions between different mechanical modes. Our work will enable the exploration of many-body effects in nanoparticle arrays with programmable cavity-mediated interactions, generating entanglement of motion, and the use of interacting particle arrays for optomechanical sensing.
A gut microbial signature for combination immune checkpoint blockade across cancer types
Authors: Gunjur Ashray , Shao Yan , Rozday Timothy , Klein Oliver , Mu Andre , Haak Bastiaan W. , Markman Ben , Kee Damien , Carlino Matteo S. , Underhill Craig , Frentzas Sophia , Michael Michael , Gao Bo , Palmer Jodie , Cebon Jonathan , Behren Andreas , Adams David J. , Lawley Trevor D. 
Published: March 2024

AbstractImmune checkpoint blockade (ICB) targeting programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte protein 4 (CTLA-4) can induce remarkable, yet unpredictable, responses across a variety of cancers. Studies suggest that there is a relationship between a cancer patient’s gut microbiota composition and clinical response to ICB; however, defining microbiome-based biomarkers that generalize across cohorts has been challenging. This may relate to previous efforts quantifying microbiota to species (or higher taxonomic rank) abundances, whereas microbial functions are often strain specific. Here, we performed deep shotgun metagenomic sequencing of baseline fecal samples from a unique, richly annotated phase 2 trial cohort of patients with diverse rare cancers treated with combination ICB (n = 106 discovery cohort). We demonstrate that strain-resolved microbial abundances improve machine learning predictions of ICB response and 12-month progression-free survival relative to models built using species-rank quantifications or comprehensive pretreatment clinical factors. Through a meta-analysis of gut metagenomes from a further six comparable studies (n = 364 validation cohort), we found cross-cancer (and cross-country) validity of strain–response signatures, but only when the training and test cohorts used concordant ICB regimens (anti-PD-1 monotherapy or combination anti-PD-1 plus anti-CTLA-4). This suggests that future development of gut microbiome diagnostics or therapeutics should be tailored according to ICB treatment regimen rather than according to cancer type.
Insight into antioxidant and anti-inflammatory effects of marine bacterial natural exopolysaccharide (EPSSM) using carrageenan-induced paw edema in rats
Authors: El awady Mohamed E. , Mohamed Sahar S. , Abo Elsoud Mostafa M. , Mahmoud Manal G. , Anwar Mai M. , Ahmed Mahgoub M. , Eltaher Ashraf , Magdeldin Sameh , Attallah Ashraf , Elhagry Ali E. , Abdelhamid Sayeda A. 
Published: March 2024

AbstractInflammation is a part of the body’s intricate biological reaction to noxious stimuli and defensive reactions. So, the aim of this investigation was to study the anti-inflammatory activity of exopolysaccharide (EPSSM) using carrageenan-induced paw edema in rats. A halophilic bacterial strain was isolated from marine sediments in the Red Sea in Egypt. The isolate has been visually and physiologically recognized, as well as by analyzing its 16S rRNA gene, which confirms Kocuria sp. clone Asker4. This particular isolate can be referenced using the accession number OL798051.1. EPSSM was subjected to purification and fractionation by a DEAE-cellulose column. Preliminary chemical analysis of EPSSM indicated that the monosaccharides were fructose, glucuronic acid, and xylose, with 2.0, 0.5, and 1.0, respectively. The antioxidant potential of EPSSM was investigated, and it was discovered that the level of activity increased independently of the concentrations, reaching a maximum threshold of 94.13% at 100 µg/mL of EPSSM for 120 min. Also, EPSSM at 50 mg/kg orally produced a significant anti-inflammatory effect on the carrageenan model at 2, 3, and 4 intervals. The EPSSM intervention resulted in reductions in the levels of catalase and superoxide dismutase enzymes, as well as a decrease in glutathione. Furthermore, the levels of nitric oxide, lipid peroxidation, and reactive oxygen species resulting from carrageenan-induced edema showed a significant reduction subsequent to the administration of EPSSM. Moreover, the findings indicated that the protein expression levels of cyclooxygenase-2 and interleukin-6 were reduced following treatment with EPSSM, resulting in a reduction of paw edema.
Preliminary assessment of new single and blended volatile binding media for temporary consolidation of cultural heritage
Authors: Kotb Hamada Sadek , Saccani Andrea , Vallet Jean-Marc , Franzoni Elisa 
Published: March 2024

AbstractVolatile Binding Media (VBM) are waxy solids that can be used for temporary consolidation of heritage artifacts and architectural surfaces thanks to their spontaneous sublimation at room temperature. They are used to temporary shelter, consolidate or protect materials during high-risk operation, such as excavation, transportation, water-based treatments, etc. Although they are employed since the 1990s, research focused almost entirely on one of them, cyclododecane (CDD), which is by far the most used in onsite applications. However, CDD exhibits some drawbacks, including a fixed sublimation speed that hardly fits into all the possible applications and climates, hence the development of new VBM is strongly needed. In recent years, a certain attention was addressed to menthol as a possible alternative, but the research on other possible substitutes is still lacking. In this paper, a range of different VBM for temporary consolidation of cultural heritage materials was prepared and investigated, including five pure compounds (CDD, cyclododecanol, cyclododecanone, menthol and camphene) and fifteen mixes. These new materials are expected to provide tunable properties in terms of melting temperatures and sublimation rates, allowing their use in a variety of climatic contexts and applications, and to exhibit better properties for onsite applications compared to CDD, such as lower flash point, lower hazard for conservators’ health and/or higher availability.
Neurobiologically realistic neural network enables cross-scale modeling of neural dynamics
Authors: Chang Yin-Jui , Chen Yuan-I , Yeh Hsin-Chih , Santacruz Samantha R. 
Published: March 2024

AbstractFundamental principles underlying computation in multi-scale brain networks illustrate how multiple brain areas and their coordinated activity give rise to complex cognitive functions. Whereas brain activity has been studied at the micro- to meso-scale to reveal the connections between the dynamical patterns and the behaviors, investigations of neural population dynamics are mainly limited to single-scale analysis. Our goal is to develop a cross-scale dynamical model for the collective activity of neuronal populations. Here we introduce a bio-inspired deep learning approach, termed NeuroBondGraph Network (NBGNet), to capture cross-scale dynamics that can infer and map the neural data from multiple scales. Our model not only exhibits more than an 11-fold improvement in reconstruction accuracy, but also predicts synchronous neural activity and preserves correlated low-dimensional latent dynamics. We also show that the NBGNet robustly predicts held-out data across a long time scale (2 weeks) without retraining. We further validate the effective connectivity defined from our model by demonstrating that neural connectivity during motor behaviour agrees with the established neuroanatomical hierarchy of motor control in the literature. The NBGNet approach opens the door to revealing a comprehensive understanding of brain computation, where network mechanisms of multi-scale activity are critical.
Analysis of the efficacy of sleeve gastrectomy, one-anastomosis gastric bypass, and single-anastomosis sleeve ileal bypass in the treatment of metabolic syndrome
Authors: Yu Hang , Qian Lulu , Yan Yu , Yang Qi , Shan Xiaodong , Chen Youwei , Fu Xiao , Chu Xuehui , Kang Xing , Sun Xitai 
Published: March 2024

AbstractThe objective of this study was to evaluate and compare the effectiveness of three different types of bariatric surgeries, namely, sleeve gastrectomy (SG), one-anastomotic gastric bypass (OAGB), and single anastomosis sleeve ileal (SASI) bypass, in the treatment of metabolic syndrome (MS). The optimal approach for managing MS remains uncertain, and thus this study aimed to provide a recent analysis of the efficacy of these surgical procedures. This retrospective study evaluated data of individuals who underwent SG, OAGB, and SASI bypass. The primary outcome measures included weight, body mass index (BMI), glucolipid metabolic index, and the occurrence of treatment-related complications within 6 to 12 months post-surgery. A total of 324 patients were included in this study. Of these, 264 patients underwent SG, 30 underwent OAGB, and 30 underwent SASI bypass. A significant decrease in weight was observed at the 6-month and 12-month marks following all three surgical procedures. Of these, patients who underwent SASI bypass exhibited the greatest reduction in weight and BMI post-surgery. Furthermore, the SASI bypass was associated with a significantly higher percentage of total weight loss (%TWL) and excess body mass index loss (%EBMIL) compared to SG and OAGB. Patients who underwent OAGB and SASI bypass demonstrated notable improvements in type 2 diabetes mellitus (T2DM). Patients who underwent SASI bypass and OAGB experienced greater postoperative comfort and reported fewer complaints of discomfort compared to the other procedure. Based on the retrospective analysis of the data, SASI bypass was associated with greater reductions in weight and BMI, higher percentages of %TWL and %EBMIL, and better improvement in T2DM compared to SG and OAGB. Therefore, both SASI bypass and OAGB were found to be more effective than SG in the treatment of MS.
Development of a deep learning model to distinguish the cause of optic disc atrophy using retinal fundus photography
Authors: Lee Dong Kyu , Choi Young Jo , Lee Seung Jae , Kang Hyun Goo , Park Yu Rang 
Published: March 2024

AbstractThe differential diagnosis for optic atrophy can be challenging and requires expensive, time-consuming ancillary testing to determine the cause. While Leber's hereditary optic neuropathy (LHON) and optic neuritis (ON) are both clinically significant causes for optic atrophy, both relatively rare in the general population, contributing to limitations in obtaining large imaging datasets. This study therefore aims to develop a deep learning (DL) model based on small datasets that could distinguish the cause of optic disc atrophy using only fundus photography. We retrospectively reviewed fundus photographs of 120 normal eyes, 30 eyes (15 patients) with genetically-confirmed LHON, and 30 eyes (26 patients) with ON. Images were split into a training dataset and a test dataset and used for model training with ResNet-18. To visualize the critical regions in retinal photographs that are highly associated with disease prediction, Gradient-Weighted Class Activation Map (Grad-CAM) was used to generate image-level attention heat maps and to enhance the interpretability of the DL system. In the 3-class classification of normal, LHON, and ON, the area under the receiver operating characteristic curve (AUROC) was 1.0 for normal, 0.988 for LHON, and 0.990 for ON, clearly differentiating each class from the others with an overall total accuracy of 0.93. Specifically, when distinguishing between normal and disease cases, the precision, recall, and F1 scores were perfect at 1.0. Furthermore, in the differentiation of LHON from other conditions, ON from others, and between LHON and ON, we consistently observed precision, recall, and F1 scores of 0.8. The model performance was maintained until only 10% of the pixel values of the image, identified as important by Grad-CAM, were preserved and the rest were masked, followed by retraining and evaluation.
A novel T cell-redirecting anti-GPRC5D × CD3 bispecific antibody with potent antitumor activity in multiple myeloma preclinical models
Authors: Tomita Urara , Ishimoto Yoko , Ri Masaki , Kawase Yumi , Hizukuri Yoshiyuki , Maru Chikako , Nanai Kayoko , Nakamura Ryuichi , Nakayama Makiko , Oguchi-Oshima Keiko , Sumi Hiroyuki , Ohtsuka Toshiaki , Iida Shinsuke , Agatsuma Toshinori 
Published: March 2024

AbstractG-protein-coupled receptor class 5 member D (GPRC5D) is detected in malignant plasma cells in approximately 90% of patients diagnosed with multiple myeloma (MM). Here, we constructed BsAb5003, a novel humanized bispecific monoclonal antibody targeting CD3 and GPRC5D, and evaluated its therapeutic impact on MM. BsAb5003 induced specific cytotoxicity of GPRC5D-positive MM cells with concomitant T cell activation and cytokine release. The efficacy of BsAb5003 was associated with GPRC5D expression levels in MM cell lines. Flow cytometry analysis of bone marrow mononuclear cells (BMMNCs) from 49 MM patients revealed that GPRC5D was expressed in a wide population of MM patients, including heavily treated and high-risk patients. In ex vivo assays using BMMNCs, BsAb5003 induced potent efficacy against CD138 + MM cells in both newly diagnosed and relapsed/refractory patient samples in a GPRC5D expression-dependent manner. BsAb5003 significantly enhanced T cell activation and cytokine production in combination with immunomodulatory drugs (IMiDs) against MM cell lines. BsAb5003 also demonstrated significant inhibition of in vivo tumor growth by recruiting T cells. Taken together, these results suggest that T cell-redirecting bispecific antibody targeting GPRC5D as monotherapy and combination therapy with IMiDs could be a highly potent and effective treatment approach for a wide population of MM patients.