bluuebunny/crossref_metadata_2025_split huggingface dataset:
Priming transcranial direct current stimulation for improving hemiparetic upper limb in patients with subacute stroke: study protocol for a randomised controlled trial
Authors: Zhu Feifei , Xu Xiaojing , Jin Minxia , Chen Jiahui , Feng Xiaoqing , Wang Jiaren , Yu Dan , Wang Rong , Lian Yijie , Huai Baoyu , Lou Xiaoyu , Shi Xiaoyu , He Ting , Lu Jiani , Zhang Jack Jiaqi , Bai Zhongfei 
Published: February 2024

IntroductionTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates brain states by applying a weak electrical current to the brain cortex. Several studies have shown that anodal stimulation of the ipsilesional primary motor cortex (M1) may promote motor recovery of the affected upper limb in patients with stroke; however, a high-level clinical recommendation cannot be drawn in view of inconsistent findings. A priming brain stimulation protocol has been proposed to induce stable modulatory effects, in which an inhibitory stimulation is applied prior to excitatory stimulation to a brain area. Our recent work showed that priming theta burst magnetic stimulation demonstrated superior effects in improving upper limb motor function and neurophysiological outcomes. However, it remains unknown whether pairing a session of cathodal tDCS with a session of anodal tDCS will also capitalise on its therapeutic effects.Methods and analysisThis will be a two-arm double-blind randomised controlled trial involving 134 patients 1–6 months after stroke onset. Eligible participants will be randomly allocated to receive 10 sessions of priming tDCS+robotic training, or 10 sessions of non-priming tDCS+robotic training for 2 weeks. The primary outcome is the Fugl-Meyer Assessment-upper extremity, and the secondary outcomes are the Wolf Motor Function Test and Modified Barthel Index. The motor-evoked potentials, regional oxyhaemoglobin level and resting-state functional connectivity between the bilateral M1 will be acquired and analysed to investigate the effects of priming tDCS on neuroplasticity.Ethics and disseminationThe study has been approved by the Research Ethics Committee of the Shanghai Yangzhi Rehabilitation Center (reference number: Yangzhi2023-022) and will be conducted in accordance with the Declaration of Helsinki of 1964, as revised in 2013.Trial registration numberChiCTR2300074681.
Efficacy and safety of autologous tumor-infiltrating lymphocytes in recurrent or refractory ovarian cancer, colorectal cancer, and pancreatic ductal adenocarcinoma
Authors: Amaria Rodabe , Knisely Anne , Vining David , Kopetz Scott , Overman Michael J , Javle Milind , Antonoff Mara B , Tzeng Ching-Wei D , Wolff Robert A , Pant Shubham , Lito Kathryn , Rangel Kelly , Fellman Bryan , Yuan Ying , Lu Karen H , Sakellariou-Thompson Donastas , Haymaker Cara L , Forget Marie-Andrée , Hwu Patrick , Bernatchez Chantale , Jazaeri Amir A 
Published: February 2024

BackgroundTumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors. Our preclinical work demonstrated more robust CD8 predominant TIL production when agonistic anti-4-1BB and CD3 antibodies were used in early ex vivo TIL culture.MethodsPatients with treatment-refractory metastatic colorectal (CRC), pancreatic (PDAC) and ovarian (OVCA) cancers were eligible. Lymphodepleting chemotherapy was followed by infusion of ex vivo expanded TIL, manufactured at MD Anderson Cancer Center with IL-2 and agonistic stimulation of CD3 and 4-1BB (urelumab). Patients received up to six doses of high-dose IL-2 after TIL infusion. Primary endpoint was evaluation of objective response rate at 12 weeks using Response Evaluation Criteria in Solid Tumors version 1.1 with secondary endpoints including disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival (OS), and safety.Results17 patients underwent TIL harvest and 16 were treated on protocol (NCT03610490), including 8 CRC, 5 PDAC, and 3 OVCA patients. Median age was 57.5 (range 33–70) and 50% were females. Median number of lines of prior therapy was 2 (range 1–8). No responses were observed at 12 weeks. Ten subjects achieved at least one stable disease (SD) assessment for a DCR of 62.5% (95% CI 35.4% to 84.8%). Best response included prolonged SD in a patient with PDAC lasting 17 months. Median PFS and OS across cohorts were 2.53 months (95% CI 1.54 to 4.11) and 18.86 months (95% CI 4.86 to NR), respectively. Grade 3 or higher toxicities attributable to therapy were seen in 14 subjects (87.5%; 95% CI 61.7% to 98.4%). Infusion product analysis showed the presence of effector memory cells with high expression of CD39 irrespective of tumor type and low expression of checkpoint markers.ConclusionsTIL manufactured with assistance of 4-1BB and CD3 agonism is feasible and treatment is associated with no new safety signals. While no responses were observed, a significant portion of patients achieved SD suggesting early/partial immunological effect. Further research is required to identify factors associated with resistance and functionally enhance T cells for a more effective therapy.
Harmonization of tumor mutation burden testing with comprehensive genomic profiling assays: an IQN Path initiative
Authors: Esposito Abate Riziero , Pasquale Raffaella , Sacco Alessandra , Simeon Vittorio , Maiello Monica Rosaria , Frezzetti Daniela , Chiodini Paolo , Normanno Nicola 
Published: February 2024

BackgroundAlthough conflicting results emerged from different studies, the tumor mutational burden (TMB) appears as one of most reliable biomarkers of sensitivity to immune checkpoint inhibitors. Several laboratories are reporting TMB values when performing comprehensive genomic profiling (CGP) without providing a clinical interpretation, due to the lack of validated cut-off values. The International Quality Network for Pathology launched an initiative to harmonize TMB testing with CGP assay and favor the clinical implementation of this biomarker.MethodsTMB evaluation was performed with three commercially available CGP panels, TruSight Oncology 500 (TSO500), Oncomine Comprehensive Plus Assay (OCA) and QIAseq Multimodal Panel (QIA), versus the reference assay FoundationOne CDx (F1CDx). Archived clinical samples derived from 60 patients with non-small cell lung cancer were used for TMB assessment. Adjusted cut-off values for each panel were calculated.ResultsTesting was successful for 91.7%, 100%, 96.7% and 100% of cases using F1CDx, TSO500, OCA and QIA, respectively. The matrix comparison analysis, between the F1CDx and CGP assays, showed a linear correlation for all three panels, with a higher correlation between F1CDx and TSO500 (rho=0.88) than in the other two comparisons (rho=0.77 for QIA; 0.72 for OCA). The TSO500 showed the best area under the curve (AUC, value 0.96), with a statistically significant difference when compared with the AUC of OCA (0.83, p value=0.01) and QIA (0.88, p value=0.028). The Youden Index calculation allowed us to extrapolate TMB cut-offs of the different panels corresponding to the 10 mutations/megabase (muts/Mb) cut-off of F1CDx: 10.19, 10.4 and 12.37 muts/Mb for TSO500, OCA and QIA, respectively. Using these values, we calculated the relative accuracy measures for the three panels. TSO500 showed 86% specificity and 96% sensitivity, while OCA and QIA had lower yet similar values of specificity and sensitivity (73% and 88%, respectively).ConclusionThis study estimated TMB cut-off values for commercially available CGP panels. The results showed a good performance of all panels on clinical samples and the calculated cut-offs support better accuracy measures for TSO500. The validated cut-off values can drive clinical interpretation of TMB testing in clinical research and clinical practice.
Comprehensive multiplexed autoantibody profiling of patients with advanced urothelial cancer
Authors: Ravi Praful , Freeman Dory , Thomas Jonathan , Ravi Arvind , Mantia Charlene , McGregor Bradley A , Berchuck Jacob E , Epstein Ilana , Budde Petra , Ahangarian Abhari Behnaz , Rupieper Elena , Gajewski Jana , Schubert Ann-Sophie , Kilian Annika L , Bräutigam Manuel , Zucht Hans-Dieter , Sonpavde Guru 
Published: February 2024

BackgroundComprehensive profiling of autoantibodies (AAbs) in metastatic urothelial cancer (mUC) has not been performed to date. This may aid in diagnosis of UC, uncover novel therapeutic targets in this disease as well as identify associations between AAbs and response and toxicity to systemic therapies.MethodsWe used serum from patients with mUC collected prior to and after systemic therapy (immune checkpoint inhibitor (ICI) or platinum-based chemotherapy (PBC)) at Dana-Farber Cancer Institute. 38 age-matched and sex-matched healthy controls (HCs) from healthy blood donors were also evaluated. The SeroTag immuno-oncology discovery array (Oncimmune) was used, with quantification of the AAb reactivity toward 1132 antigens. Bound AAbs were detected using an anti-immunoglobulin G-specific detection antibody conjugated to the fluorescent reporter dye phycoerythrin. The AAb reactivity was reported as the median fluorescence intensity for each color and sample using a Luminex FlexMAP3D analyzer. Clinical outcomes of interest included radiographic response and development of immune-related adverse events (irAEs). Significance analysis of microarray was used to compare mUC versus HC and radiographic response. Associations with irAE were evaluated using a logistic regression model. P<0.05 was considered statistically significant.Results66 patients were included with a median age of 68 years; 54 patients (82%) received ICI and 12 patients (18%) received PBC. Compared with HCs, AAbs against the cancer/testis antigens (CTAG1B, CTAG2, MAGEB18), HSPA1A, TP53, KRAS, and FGFR3 were significantly elevated in patients with mUC. AAbs against BRCA2, TP53, and CTNBB1 were associated with response, and those against BICD2 and UACA were associated with resistance to ICI therapy. AAbs against MITF, CDH3, and KDM4A were associated with development of irAEs in patient who received an ICI. A higher variance in pre-to-post treatment fold change in AAb levels was seen in patients treated with ICI versus PBC and was associated with response to ICI.ConclusionsThis is the first report of comprehensive AAb profiling of patients with mUC and identified key AAbs that were elevated in patients with mUC versus HCs as well as AAbs associated with therapeutic response to ICI. These findings are hypothesis generating and further mechanistic studies evaluating humoral immunity in UC are required.
Distinguishing Legendrian knots in topological types 74, 948, 10136 with maximal Thurston–Bennequin number
Authors: Prasolov Maxim , Shastin Vladimir 
Published: February 2024

In a recent work of Dynnikov and Prasolov [I. Dynnikov and M. Prasolov, An algorithm for comparing Legendrian knots, preprint (2023), arXiv:2309.05087] a new method of comparing Legendrian knots with nontrivial symmetry group is proposed. Using this method, we confirm conjectures of [W. Chongchitmate and L. Ng, An atlas of Legendrian knots, Exp. Math. 22(1) (2013) 26–37, arXiv:1010.3997] about Legendrian knots in topological types [Formula: see text], [Formula: see text] and [Formula: see text]. This completes the classification of Legendrian types of rectangular diagrams of knots of complexity up to 9.
Quantum confinement effects on the structural and optical properties of nanostructured tin oxide powder
Authors: Besahraoui Fatiha , Chebbah Kheira 
Published: February 2024

Nanostructured Tin oxide powders, prepared by chemical precipitation method, exhibit interesting structural and optical properties at nanoscale dimensions. Structural characterization confirmed the formation of pure nanostructured SnO2 powders with average crystalline grain size of 54.4[Formula: see text]nm calculated with relative uncertainty of 1.62%. The optical properties of nanoSnO2 powder performed by using transmittance and photoluminescence measurements reveal high transparency and multi-photon emissions in visible and ultraviolet regions. The different photon emissions are attributed to radiative transitions via oxygen vacancies, Sn interstitials, Sn substitutional and dangling bonds. The lower wavelength value corresponded to the absorption edge peak indicating the good quantum confinement of nanostructured SnO2 powder. The larger optical band gap, calculated through transmittance measurements, confirms the quantum confinement effects. The presence of quantum confinement and native point defects in nanostructured SnO2 powders can contribute to enhancing photon emissions process. This result may offer inherent advantages over conventional materials for photonic quantum information technology. The sustained photon emission at room temperature, indicates that SnO2 nanoparticles could be useful in room temperature quantum computing and can maintain the delicate quantum states required for computation at higher temperatures.
A Product-form Network for Systems with Job Stealing Policies
Authors: Olliaro Diletta , Casale Giuliano , Marin Andrea , Rossi Sabina 
Published: February 2024

In queueing networks, product-form solutions are of fundamental importance to efficiently compute performance metrics in complex models of computer systems. The product-form property entails that the steady-state probabilities of the joint stochastic process underlying the network can be expressed as the normalized product of functions that only depend on the local state of the components. In many relevant cases, product-forms are the only way to perform exact quantitative analyses of large systems.
In this work, we introduce a novel class of product-form queueing networks where servers are always busy. Applications include model of systems where successive refinements on jobs improve the processes quality but are not strictly required to obtain a result. To this aim, we define a job movement policy that admits instantaneous migrations of jobs from non-empty waiting buffers to empty ones. Thus, the resulting routing scheme is state-dependent. This class of networks maximizes the system throughput.
This model can be implemented with arbitrary topology, including feedback, and both in an open and closed setting. As far as closed systems are concerned, we give a convolution algorithm and the corresponding mean value analysis to compute expected performance indices for closed models.
Curiosity Satisfaction Increases Event-related Potentials Sensitive to Reward
Authors: Rüterbories Tim , Mecklinger Axel , Eschmann Kathrin C. J. , Crivelli-Decker Jordan , Ranganath Charan , Gruber Matthias J. 
Published: February 2024

Abstract
Successful learning depends on various factors such as depth of processing, motivation, or curiosity about information. A strong drive to learn something or the expectation of receiving a reward can be crucial to enhance learning. However, the influence of curiosity on the processing of new information and its similarity with reward processing is not well understood. This study examined whether states of curiosity influence specific ERPs associated with reward processing and whether these ERPs are related with later memory benefits. In an initial screening phase, participants indicated their curiosity and confidence in prior knowledge about answers to various trivia questions. In a subsequent study phase, we targeted different time windows related to reward processing during the presentation of trivia answers containing the reward positivity (RewP; 250–350 msec), the P3 (250–500 msec), and the late-positive-potential (LPP; 600–1000 msec). In a following surprise memory test, we found that participants recalled more high- than low-curiosity answers. The RewP, P3, and LPP showed greater positive mean amplitudes for high compared with low curiosity, reflecting increased reward processing. In addition, we found that the RewP and the P3 showed more positive mean amplitudes for later recalled compared with later forgotten answers, but curiosity did not modulate this encoding-related results. These findings support the view that the satisfaction of curiosity resembles reward processing, indicated by ERPs.
Neural Correlates of Analogical Reasoning on Syntactic Patterns
Authors: Li Zhongshan , Zhou Zhuqian , Wang Xiaoling , Wu Jinshan , Chen Luyao 
Published: February 2024

Abstract
Analogical reasoning is central to thought and learning. However, previous neuroscience studies have focused mainly on neural substrates for visuospatial and semantic analogies. There has not yet been research on the neural correlates of analogical reasoning on syntactic patterns generated by the syntactic rules, a key feature of human language faculty. The present investigation took an initial step to address this paucity. Twenty-four participants, whose brain activity was monitored by fMRI, engaged in first-order and second-order relational judgments of syntactic patterns as well as simple and complex working memory tasks. After scanning, participants rated the difficulty of each step during analogical reasoning; these ratings were related to signal intensities in activated regions of interest using Spearman correlation analyses. After prior research, differences in activation levels during second-order and first-order relational judgments were taken as evidence of analogical reasoning. These analyses showed that analogical reasoning on syntactic patterns recruited brain regions consistent with those supporting visuospatial and semantic analogies, including the anterior and posterior parts of the left middle frontal gyrus, anatomically corresponding to the left rostrolateral pFC and the left dorsolateral pFC. The correlation results further revealed that the posterior middle frontal gyrus might be involved in analogical access and mapping with syntactic patterns. Our study is the first to investigate the process of analogical reasoning on syntactic patterns at the neurobiological level and provide evidence of the specific functional roles of related regions during subprocesses of analogical reasoning.
Automated Cephalometric Landmark Detection: A Novel Software Model Compared with Manual Annotation Method
Authors: S. Jishnu , Kurian Binnoy , Michael Tony 
Published: February 2024

Introduction AI-based automated cephalometric landmark detection streamlines orthodontic diagnosis and treatment planning, providing accurate, efficient, and reliable results. Benefits include saving time, minimizing subjectivity, improving precision, and facilitating continuous improvement. However, they should complement clinician expertise, ensuring qualified orthodontists make the final diagnosis and treatment plan. Aim To propose a method that automatically detects cephalometric landmarks on the X-ray images and compare these values with the manual annotation method. Methodology A dataset of 600 X-ray images, each containing 19 landmarks, was collected. Two orthodontists manually marked the 19 landmarks in 300 cephalograms and their coordinates were automatically extracted. The dataset was cleaned for errors, and a pre-trained CNN model with an EfficientNetB7 backbone was used for landmark detection. The model was trained on 80% of the dataset and tested on the remaining 20%. The two-step method included ROI extraction and landmark detection. The RMSE score was used to evaluate inter-examiner reliability and the R2 score was used to compare manual and automated models. Result Model landmark locations were compared to the manual method. The mean deviation of the predicted landmarks from the actual landmarks was calculated using RMSE, and the model showed acceptable accuracy compared to manual annotation. EfficientNetB7 was found to have detection accuracies similar to the manual annotation method. For landmarks like Porion, articulare, and soft tissue pogonion, the model outperformed the human annotation method and provides a consistent better result, and for points like Point A, pogonion, gnathion, and menton, the manual methods show more accurate results. Conclusion The study introduced an automated approach using deep learning to predict landmark locations, and the results demonstrate its accuracy in comparison with the manual annotation method. This approach effectively detects cephalometric landmarks, suggesting its potential for clinical use with orthodontist’s supervision.
A fall into the pit, a gain in your wit: Top managerial career setback experience and accounting conservatism
Authors: Su Zhong-qin , Zhu Yiting , Su Wunhong , Xiao Zuoping 
Published: February 2024

This study investigates the relationship between chief executive officers (CEOs) and chief financial officers (CFOs) with career setbacks and firms’ accounting conservatism. Using manually collected data from Chinese listed firms, this study finds that firms run by CEOs/CFOs who experienced career setbacks adopt more conservative accounting policies. In addition, the degree and timing of career setbacks and the experience of demotion and penalization by regulations affect CEOs’/CFOs’ decision-making. The results are robust to a battery of checks and analyses, including the propensity score matching procedure, the difference-in-differences method, and alternative measures. Further evidence suggests that the positive association between CEOs/CFOs with career setbacks and firms’ accounting conservatism is more pronounced at firms with better corporate governance, effective internal control, and higher financial constraints. This study also shows that financially conservative firms have more cash holding, which is positively correlated with career setbacks. JEL Classification: G34, M41, G41
Improvement of migraine depressive symptoms is not related to headache frequency: exploring the impact of anti-CGRP therapies
Authors: Torres-Ferrús Marta , Gallardo Victor J. , Alpuente Alicia , Caronna Edoardo , Giné-Ciprés Eulalia , Pozo-Rosich Patricia 
Published: February 2024

Background The present study aimed to describe the prevalence and evolution of depressive symptoms in a cohort of migraine patients treated with anti-CGRP monoclonal antibodies. Methods This is an exploratory, prospective, unicentric, one-year longitudinal study. We included migraine patients who started treatment with anti-CGRP monoclonal antibodies. Baseline demographic data, medical history, concomitant medication and migraine characteristics were collected. The presence of depressive symptoms was evaluated using the Beck Depression Inventory-II quarterly and treatment response was categorized according to the reduction in monthly headache days. A generalized mixed-effect regression model was used to model depression score over a one-year treatment taking into account frequency response rates. Results We included 577 patients: 84.2% females; median (range) age 47.0 (39.0–53.0) years, 46.1% (266/577) of them presented depressive symptoms at baseline (16.1% mild, 13.3% moderate and 16.6% severe). After six-month treatment, 47.4% (126/266) reduced headache frequency ≥50% after one year and 63.5% (169/266) achieved a clinically significant improvement in depression symptoms. We observed a 30.8% (−50.0%, −3.2%) main reduction in depression score during the first quarter. The improvement in depression symptoms was independently associated with headache frequency response: non-responders, −25.0% (−43.9%, −1.1%); partial responders, −30.2% (−51.3%, −7.6%); and good responders, −33.3% (−54.6%, −7.5%). Conclusions Anti-CGRP monoclonal antibodies targeting CGRP are effective in reducing depressive symptoms in patients with migraine. The main change of depression score happens during the first three months of treatment. The reduction in depressive symptoms is independent of migraine frequency improvement.