bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses
Authors: Friedman Claire F. , Manning-Geist Beryl L. , Zhou Qin , Soumerai Tara , Holland Aliya , Da Cruz Paula Arnaud , Green Hunter , Ozsoy Melih Arda , Iasonos Alexia , Hollmann Travis , Leitao Mario M. , Mueller Jennifer J. , Makker Vicky , Tew William P. , O’Cearbhaill Roisin E. , Liu Ying L. , Rubinstein Maria M. , Troso-Sandoval Tiffany , Lichtman Stuart M. , Schram Alison , Kyi Chrisann , Grisham Rachel N. , Causa Andrieu Pamela , Wherry E. John , Aghajanian Carol , Weigelt Britta , Hensley Martee L. , Zamarin Dmitriy 
Published: April 2024

AbstractProgrammed death-1 (PD-1) inhibitors are approved for therapy of gynecologic cancers with DNA mismatch repair deficiency (dMMR), although predictors of response remain elusive. We conducted a single-arm phase 2 study of nivolumab in 35 patients with dMMR uterine or ovarian cancers. Co-primary endpoints included objective response rate (ORR) and progression-free survival at 24 weeks (PFS24). Secondary endpoints included overall survival (OS), disease control rate (DCR), duration of response (DOR) and safety. Exploratory endpoints included biomarkers and molecular correlates of response. The ORR was 58.8% (97.5% confidence interval (CI): 40.7–100%), and the PFS24 rate was 64.7% (97.5% one-sided CI: 46.5–100%), meeting the pre-specified endpoints. The DCR was 73.5% (95% CI: 55.6–87.1%). At the median follow-up of 42.1 months (range, 8.9–59.8 months), median OS was not reached. One-year OS rate was 79% (95% CI: 60.9–89.4%). Thirty-two patients (91%) had a treatment-related adverse event (TRAE), including arthralgia (n = 10, 29%), fatigue (n = 10, 29%), pain (n = 10, 29%) and pruritis (n = 10, 29%); most were grade 1 or grade 2. Ten patients (29%) reported a grade 3 or grade 4 TRAE; no grade 5 events occurred. Exploratory analyses show that the presence of dysfunctional (CD8+PD-1+) or terminally dysfunctional (CD8+PD-1+TOX+) T cells and their interaction with programmed death ligand-1 (PD-L1)+ cells were independently associated with PFS24. PFS24 was associated with presence of MEGF8 or SETD1B somatic mutations. This trial met its co-primary endpoints (ORR and PFS24) early, and our findings highlight several genetic and tumor microenvironment parameters associated with response to PD-1 blockade in dMMR cancers, generating rationale for their validation in larger cohorts.ClinicalTrials.gov identifier: NCT03241745.
Association between inflammation-based prognostic markers and mortality after hip replacement
Authors: Oh Ah Ran , Kwon Ji-Hye , Jin Gayoung , Kong So Myung , Lee Dong Jae , Park Jungchan 
Published: April 2024

AbstractWe aimed to evaluate the association between inflammation-based prognostic markers and mortality after hip replacement. From March 2010 to June 2020, we identified 5,369 consecutive adult patients undergoing hip replacement with C-reactive protein (CRP), albumin, and complete blood count measured within six months before surgery. Receiver operating characteristic (ROC) curves were generated to evaluate predictabilities and estimate thresholds of CRP-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). Patients were divided according to threshold, and mortality risk was compared. The primary outcome was one-year mortality, and overall mortality was also analyzed. One-year mortality was 2.9%. Receiver operating characteristics analysis revealed areas under the curve of 0.838, 0.832, 0.701, and 0.732 for CAR, NLR, PLR, and modified Glasgow Prognostic Score, respectively. The estimated thresholds were 2.10, 3.16, and 11.77 for CAR, NLR, and PLR, respectively. According to the estimated threshold, high CAR and NLR were associated with higher one-year mortality after adjustment (1.0% vs. 11.7%; HR = 2.16; 95% CI 1.32–3.52; p = 0.002 for CAR and 0.8% vs. 9.6%; HR = 2.05; 95% CI 1.24–3.39; p = 0.01 for NLR), but PLR did not show a significant mortality increase (1.4% vs. 7.4%; HR = 1.12; 95% CI 0.77–1.63; p = 0.57). Our study demonstrated associations of preoperative levels of CAR and NLR with postoperative mortality in patients undergoing hip replacement. Our findings may be helpful in predicting mortality in patients undergoing hip replacement.
Classification of laryngeal diseases including laryngeal cancer, benign mucosal disease, and vocal cord paralysis by artificial intelligence using voice analysis
Authors: Kim Hyun-Bum , Song Jaemin , Park Seho , Lee Yong Oh 
Published: April 2024

AbstractVoice change is often the first sign of laryngeal cancer, leading to diagnosis through hospital laryngoscopy. Screening for laryngeal cancer solely based on voice could enhance early detection. However, identifying voice indicators specific to laryngeal cancer is challenging, especially when differentiating it from other laryngeal ailments. This study presents an artificial intelligence model designed to distinguish between healthy voices, laryngeal cancer voices, and those of the other laryngeal conditions. We gathered voice samples of individuals with laryngeal cancer, vocal cord paralysis, benign mucosal diseases, and healthy participants. Comprehensive testing was conducted to determine the best mel-frequency cepstral coefficient conversion and machine learning techniques, with results analyzed in-depth. In our tests, laryngeal diseases distinguishing from healthy voices achieved an accuracy of 0.85–0.97. However, when multiclass classification, accuracy ranged from 0.75 to 0.83. These findings highlight the challenges of artificial intelligence-driven voice-based diagnosis due to overlaps with benign conditions but also underscore its potential.
Four-dimensional conditional averaging tomography of rotating plasma ejection from cylindrical detached plasma
Authors: Tanaka Hirohiko , Kajita Shin , Natsume Hiroki , Ohno Noriyasu 
Published: April 2024

AbstractDetached plasma formation is a way to reduce the heat load on the wall in magnetic fusion devices. This study proposes a novel analysis technique consisting of the conditional averaging, sliding window, and tomography to reveal the spatiotemporal behavior of the rotating radial ejection event of detached plasma, which further contributes to local heat load reduction. The used equipment is a high-speed camera and an electrostatic probe located at the periphery of the linear plasma device NAGDIS-II. By applying this method, four-dimensional (4D) behavior of the emission structure along time (1D) and space perpendicular and parallel to the magnetic field (3D) was clarified; a rotating distorted structure appears as a precursor, which is then scraped and transported radially and axially. The proposed method is widely applicable to short-term rigid-body rotating structures, especially in linear plasmas.
Experimental evaluation of accuracy and efficiency of two control strategies for a novel foot commanded robotic laparoscope holders with surgeons
Authors: Yang Yan-Jun , Vadivelu Arvind Kumar N , Hepworth Jessica , Zeng Yongpeng , Pilgrim Charles H. C. , Kulic Dana , Abdi Elahe 
Published: April 2024

AbstractThe implementation of a laparoscope-holding robot in minimally invasive surgery enhances the efficiency and safety of the operation. However, the extra robot control task can increase the cognitive load on surgeons. A suitable interface may simplify the control task and reduce the surgeon load. Foot interfaces are commonly used for commanding laparoscope-holding robots, with two control strategies available: decoupled control permits only one Cartesian axis actuation, known as decoupled commands; hybrid control allows for both decoupled commands and multiple axes actuation, known as coupled commands. This paper aims to determine the optimal control strategy for foot interfaces by investigating two common assumptions in the literature: (1) Decoupled control is believed to result in better predictability of the final laparoscopic view orientation, and (2) Hybrid control has the efficiency advantage in laparoscope control. Our user study with 11 experienced and trainee surgeons shows that decoupled control has better predictability than hybrid control, while both approaches are equally efficient. In addition, using two surgery-like tasks in a simulator, users’ choice of decoupled and coupled commands is analysed based on their level of surgical experience and the nature of the movement. Results show that trainee surgeons tend to issue more commands than the more experienced participants. Single decoupled commands were frequently used in small view adjustments, while a mixture of coupled and decoupled commands was preferred in larger view adjustments. A guideline for foot interface control strategy selection is provided.
Spatiotemporal expression of thyroid hormone transporter MCT8 and THRA mRNA in human cerebral organoids recapitulating first trimester cortex development
Authors: Graffunder Adina Sophie , Bresser Audrey Amber Julie , Fernandez Vallone Valeria , Megges Matthias , Stachelscheid Harald , Kühnen Peter , Opitz Robert 
Published: April 2024

AbstractThyroid hormones (TH) play critical roles during nervous system development and patients carrying coding variants of MCT8 (monocarboxylate transporter 8) or THRA (thyroid hormone receptor alpha) present a spectrum of neurological phenotypes resulting from perturbed local TH action during early brain development. Recently, human cerebral organoids (hCOs) emerged as powerful in vitro tools for disease modelling recapitulating key aspects of early human cortex development. To begin exploring prospects of this model for thyroid research, we performed a detailed characterization of the spatiotemporal expression of MCT8 and THRA in developing hCOs. Immunostaining showed MCT8 membrane expression in neuronal progenitor cell types including early neuroepithelial cells, radial glia cells (RGCs), intermediate progenitors and outer RGCs. In addition, we detected robust MCT8 protein expression in deep layer and upper layer neurons. Spatiotemporal SLC16A2 mRNA expression, detected by fluorescent in situ hybridization (FISH), was highly concordant with MCT8 protein expression across cortical cell layers. FISH detected THRA mRNA expression already in neuroepithelium before the onset of neurogenesis. THRA mRNA expression remained low in the ventricular zone, increased in the subventricular zone whereas strong THRA expression was observed in excitatory neurons. In combination with a robust up-regulation of known T3 response genes following T3 treatment, these observations show that hCOs provide a promising and experimentally tractable model to probe local TH action during human cortical neurogenesis and eventually to model the consequences of impaired TH function for early cortex development.
Frequency-dependent dynamics of steady-state visual evoked potentials under sustained flicker stimulation
Authors: Łabęcki Maciej , Nowicka Maria Małgorzata , Wróbel Andrzej , Suffczynski Piotr 
Published: April 2024

AbstractSteady-state visual evoked potentials (SSVEP) are electroencephalographic signals elicited when the brain is exposed to a visual stimulus with a steady frequency. We analyzed the temporal dynamics of SSVEP during sustained flicker stimulation at 5, 10, 15, 20 and 40 Hz. We found that the amplitudes of the responses were not stable over time. For a 5 Hz stimulus, the responses progressively increased, while, for higher flicker frequencies, the amplitude increased during the first few seconds and often showed a continuous decline afterward. We hypothesize that these two distinct sets of frequency-dependent SSVEP signal properties reflect the contribution of parvocellular and magnocellular visual pathways generating sustained and transient responses, respectively. These results may have important applications for SSVEP signals used in research and brain-computer interface technology and may contribute to a better understanding of the frequency-dependent temporal mechanisms involved in the processing of prolonged periodic visual stimuli.
Co-ordinate-based positional embedding that captures resolution to enhance transformer’s performance in medical image analysis
Authors: Das Badhan Kumar , Zhao Gengyan , Islam Saahil , Re Thomas J. , Comaniciu Dorin , Gibson Eli , Maier Andreas 
Published: April 2024

AbstractVision transformers (ViTs) have revolutionized computer vision by employing self-attention instead of convolutional neural networks and demonstrated success due to their ability to capture global dependencies and remove spatial biases of locality. In medical imaging, where input data may differ in size and resolution, existing architectures require resampling or resizing during pre-processing, leading to potential spatial resolution loss and information degradation. This study proposes a co-ordinate-based embedding that encodes the geometry of medical images, capturing physical co-ordinate and resolution information without the need for resampling or resizing. The effectiveness of the proposed embedding is demonstrated through experiments with UNETR and SwinUNETR models for infarct segmentation on MRI dataset with AxTrace and AxADC contrasts. The dataset consists of 1142 training, 133 validation and 143 test subjects. Both models with the addition of co-ordinate based positional embedding achieved substantial improvements in mean Dice score by 6.5% and 7.6%. The proposed embedding showcased a statistically significant advantage p-value< 0.0001 over alternative approaches. In conclusion, the proposed co-ordinate-based pixel-wise positional embedding method offers a promising solution for Transformer-based models in medical image analysis. It effectively leverages physical co-ordinate information to enhance performance without compromising spatial resolution and provides a foundation for future advancements in positional embedding techniques for medical applications.
Spectroscopic insight into breast cancer: profiling small extracellular vesicles lipids via infrared spectroscopy for diagnostic precision
Authors: Mishra Abhay , Zehra Sadaqa , Bharti Prahalad Kumar , Mathur Sandeep R. , Ranjan Piyush , Batra Atul , Inampudi Krishna K. , Modi Gyan Prakash , Nikolajeff Fredrik , Kumar Saroj 
Published: April 2024

AbstractBreast cancer, a leading cause of female mortality due to delayed detection owing to asymptomatic nature and limited early diagnostic tools, was investigated using a multi-modal approach. Plasma-derived small EVs from breast cancer patients (BrCa, n = 74) and healthy controls (HC, n = 30) were analyzed. Small EVs (n = 104), isolated through chemical precipitation, underwent characterization via transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Validation involved antibody-based tests (TSG101, CD9, CD81, CD63). Infrared spectra of small EVs were obtained, revealing significant differences in lipid acyl chains, particularly in the C–H stretching of CH3. The study focused on the lipid region (3050–2900 cm−1), identifying peaks (3015 cm−1, 2960 cm−1, 2929 cm−1) as distinctive lipid characteristics. Spectroscopic lipid-to-lipid ratios [(I3015/I2929), (I2960/I2929)] emerged as prominent breast cancer markers. Exploration of protein, nucleic acid, and carbohydrate ratios indicated variations in alpha helices, asymmetric C–H stretching vibrations, and C–O stretching at 1033 cm−1. Principal component analysis (PCA) successfully differentiated BrCa and HC small EVs, and heatmap analysis and receiver operating characteristic (ROC) curve evaluations underscored the discriminatory power of lipid ratios. Notably, (I2960/I2929) exhibited 100% sensitivity and specificity, highlighting its potential as a robust BrCa sEV marker for breast cancer detection.
Research on fault identification of high-voltage circuit breakers with characteristics of voiceprint information
Authors: Wang Sihao , Zhou Yongrong , Ma Zhaoxing 
Published: April 2024

AbstractHigh voltage circuit breakers are one of the core equipment in power system operation, and the voiceprint signals generated during operation contain extremely rich information. This paper proposes a fault identification method for high voltage circuit breakers based on voiceprint information data. Firstly, based on the developed voiceprint information data acquisition device, the voiceprint information of a certain high voltage circuit breaker is obtained; Secondly, an improved S-transform is proposed in the article, which generates an amplitude matrix based on the S-transform of voiceprint information; Then, through the matrix Singular value decomposition method, the fault feature quantity of voiceprint information is extracted from the time–frequency angle, and the diagnosis system of the support vector machine model is established, and the system is trained to realize the fault identification of the high-voltage circuit breaker; Finally, through experimental simulation calculations, it was shown that the accuracy of the proposed fault identification method in different operating conditions reached 92.6%, verifying the good accuracy and robustness of the proposed method and equipment.
Anticancer potential of thiocolchicoside and lauric acid loaded chitosan nanogel against oral cancer cell lines: a comprehensive study
Authors: Mustafa Ameena , Indiran Meignana Arumugham , Ramalingam Karthikeyan , Perumal Elumalai , Shanmugham Rajeshkumar , Karobari Mohmed Isaqali 
Published: April 2024

AbstractThe present study explored the anticancer activity of a Chitosan-based nanogel incorporating thiocolchicoside and lauric acid (CTL) against oral cancer cell lines (KB-1). Cell viability, AO/EtBr dual staining and Cell cycle analysis were done to evaluate the impact of CTL nanogel on oral cancer cells. Real-time PCR was performed to analyze proapoptotic and antiapoptotic gene expression in CTL-treated KB-1 cells. Further, molecular docking analysis was conducted to explore the interaction of our key ingredient, thiocolchicoside and its binding affinities. The CTL nanogel demonstrated potent anticancer activity by inhibiting oral cancer cell proliferation and inducing cell cycle arrest in cancer cells. Gene expression analysis indicated alterations in Bax and Bcl-2 genes; CTL nanogel treatment increased Bax mRNA expression and inhibited the Bcl-2 mRNA expression, which showed potential mechanisms of the CTL nanogel's anticancer action. It was found that thiocolchicoside can stabilize the protein's function or restore it as a tumour suppressor. The CTL nanogel exhibited excellent cytotoxicity and potent anticancer effects, making it a potential candidate for non-toxic chemotherapy in cancer nanomedicine. Furthermore, the nanogel's ability to modulate proapoptotic gene expression highlights its potential for targeted cancer therapy. This research contributes to the growing interest in Chitosan-based nanogels and their potential applications in cancer treatment.
Activin A signaling stimulates neutrophil activation and macrophage migration in pancreatitis
Authors: Wiley Mark B. , Bauer Jessica , Alvarez Valentina , Mehrotra Kunaal , Cheng Wenxuan , Kolics Zoe , Giarrizzo Michael , Ingle Komala , Bialkowska Agnieszka B. , Jung Barbara 
Published: April 2024

AbstractAcute Pancreatitis (AP) is associated with high mortality and current treatment options are limited to supportive care. We found that blockade of activin A (activin) in mice improves outcomes in two murine models of AP. To test the hypothesis that activin is produced early in response to pancreatitis and is maintained throughout disease progression to stimulate immune cells, we first performed digital spatial profiling (DSP) of human chronic pancreatitis (CP) patient tissue. Then, transwell migration assays using RAW264.7 mouse macrophages and qPCR analysis of “neutrophil-like” HL-60 cells were used for functional correlation. Immunofluorescence and western blots on cerulein-induced pancreatitis samples from pancreatic acinar cell-specific Kras knock-in (Ptf1aCreER™; LSL-KrasG12D) and functional WT Ptf1aCreER™ mouse lines mimicking AP and CP to allow for in vivo confirmation. Our data suggest activin promotes neutrophil and macrophage activation both in situ and in vitro, while pancreatic activin production is increased as early as 1 h in response to pancreatitis and is maintained throughout CP in vivo. Taken together, activin is produced early in response to pancreatitis and is maintained throughout disease progression to promote neutrophil and macrophage activation.
Improvement of roughness in ultrasonic assisted magnetorheological finishing of small titanium alloy nuts by orthogonal test method
Authors: Bi Cheng , Ji Axiang , Wang Hongyun , Wang Haibo , Zhu Junhua , Zhou Fenfen 
Published: April 2024

AbstractTitanium alloy with high corrosion resistance, high strength-to-density ratio, and excellent biocompatibility has a wide range of applications in the field of biomedical implants. Polishing experiments of titanium alloy with a small size and complex shapes were investigated using an ultrasonic assisted magnetorheological finishing (UMRF) device excited by a three-pole magnetic field generator. The models of the normal force and the shear force were first proposed based on the Preston equation to analyze the mechanism of material removal in the UMRF process. Subsequently, the single-factor experiments using titanium alloy nuts (M3) and the MR polishing fluid with silicon carbide abrasives were carried out. Furthermore, to improve the surface roughness and the change rate of surface roughness of nuts, orthogonal tests with a standard L9(34) orthogonal array were designed and performed based on the optimized process parameters obtained from the single-factor experiment. The results indicated the effect on surface roughness and change rate of surface roughness as applied current > roller speed > ultrasonic amplitude > spindle speed and applied current > roller speed > spindle speed > ultrasonic amplitude, respectively. Moreover, the surface roughness was improved from an initial 1.247 μm to a final 0.104 μm after the polishing for 80 min under these optimal process parameters.