bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining the Tyrosine Kinase Inhibitor Cabozantinib and the mTORC1/2 Inhibitor Sapanisertib Blocks ERK Pathway Activity and Suppresses Tumor Growth in Renal Cell Carcinoma
Authors: Wu Yige , Chen Siqi , Yang Xiaolu , Sato Kazuhito , Lal Preet , Wang Yuefan , Shinkle Andrew T. , Wendl Michael C. , Primeau Tina M. , Zhao Yanyan , Gould Alanna , Sun Hua , Mudd Jacqueline L. , Hoog Jeremy , Mashl R. Jay , Wyczalkowski Matthew A. , Mo Chia-Kuei , Liu Ruiyang , Herndon John M. , Davies Sherri R. , Liu Di , Ding Xi , Evrard Yvonne A. , Welm Bryan E. , Lum David , Koh Mei Yee , Welm Alana L. , Chuang Jeffrey H. , Moscow Jeffrey A. , Meric-Bernstam Funda , Govindan Ramaswamy , Li Shunqiang , Hsieh James , Fields Ryan C. , Lim Kian-Huat , Ma Cynthia X. , Zhang Hui , Ding Li , Chen Feng 
Published: December 2023

AbstractCurrent treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced tumor regression in all models, including two from patients who experienced treatment failure with FDA-approved TKI and immunotherapy combinations. In cabozantinib-treated samples, imaging analysis revealed a significant reduction in vascular density, and single-nucleus RNA sequencing (snRNA-seq) analysis indicated a decreased proportion of endothelial cells in the tumors. SnRNA-seq data further identified a tumor subpopulation enriched with cell-cycle activity that exhibited heightened sensitivity to the cabozantinib and sapanisertib combination. Conversely, activation of the epithelial–mesenchymal transition pathway, detected at the protein level, was associated with drug resistance in residual tumors following combination treatment. The combination effectively restrained ERK phosphorylation and reduced expression of ERK downstream transcription factors and their target genes implicated in cell-cycle control and apoptosis. This study highlights the potential of the cabozantinib plus sapanisertib combination as a promising treatment approach for patients with RCC, particularly those whose tumors progressed on immune checkpoint inhibitors and other TKIs.Significance:The molecular-guided therapeutic strategy of combining cabozantinib and sapanisertib restrains ERK activity to effectively suppress growth of renal cell carcinomas, including those unresponsive to immune checkpoint inhibitors.
Facts and Hopes on Biomarkers for Successful Early Clinical Immunotherapy Trials: Innovative Patient Enrichment Strategies
Authors: Cannarile Michael A. , Karanikas Vaios , Reis Bernhard , Mancao Christoph , Lagkadinou Eleni , Rüttinger Dominik , Rieder Natascha , Ribeiro Franclim R. , Kao Henry , Dziadek Sebastian , Gomes Bruno 
Published: December 2023

Abstract
Despite the clinical validation and unequivocal benefit to patients, the development of cancer immunotherapies is facing some key challenges and the attrition rate in early phases of development remains high. Identifying the appropriate patient population that would benefit most from the drug is on the critical path for successful clinical development. We believe that a systematic implementation of patient enrichment strategies early in the drug development process and trial design, is the basis for an innovative, more efficient, and leaner clinical development to achieve earlier a clear proof of concept or proof of failure. In this position article, we will describe and propose key considerations for the implementation of patient enrichment strategies as an opportunity to provide decision-enabling data earlier in the drug development process. We introduce an innovative multidimensional tool for immuno-oncology drug development that focuses on facilitating the identification and prioritization of enrichment-relevant biomarkers, based on the drug mechanism of action. To illustrate its utility, we discuss patient enrichment examples and use a case in the field of cancer immunotherapy, together with technical and regulatory considerations. Overall, we propose to implement fit for purpose enrichment strategies for all investigational drugs as early as possible in the development process. We believe that this will increase the success rate of immuno-oncology clinical trials, and eventually bring new and better medicines to patients faster.
Cooperativity, Information Gain, and Energy Cost During Early LTP in Dendritic Spines
Authors: Karbowski Jan , Urban Paulina 
Published: December 2023

Abstract
We investigate a mutual relationship between information and energy during the early phase of LTP induction and maintenance in a large-scale system of mutually coupled dendritic spines, with discrete internal states and probabilistic dynamics, within the framework of nonequilibrium stochastic thermodynamics. In order to analyze this computationally intractable stochastic multidimensional system, we introduce a pair approximation, which allows us to reduce the spine dynamics into a lower-dimensional manageable system of closed equations. We found that the rates of information gain and energy attain their maximal values during an initial period of LTP (i.e., during stimulation), and after that, they recover to their baseline low values, as opposed to a memory trace that lasts much longer. This suggests that the learning phase is much more energy demanding than the memory phase. We show that positive correlations between neighboring spines increase both a duration of memory trace and energy cost during LTP, but the memory time per invested energy increases dramatically for very strong, positive synaptic cooperativity, suggesting a beneficial role of synaptic clustering on memory duration. In contrast, information gain after LTP is the largest for negative correlations, and energy efficiency of that information generally declines with increasing synaptic cooperativity. We also find that dendritic spines can use sparse representations for encoding long-term information, as both energetic and structural efficiencies of retained information and its lifetime exhibit maxima for low fractions of stimulated synapses during LTP. Moreover, we find that such efficiencies drop significantly with increasing the number of spines. In general, our stochastic thermodynamics approach provides a unifying framework for studying, from first principles, information encoding, and its energy cost during learning and memory in stochastic systems of interacting synapses.
Genome-wide association study of brain functional and structural networks
Authors: Cheng Ruonan , Yin Ruochen , Zhao Xiaoyu , Wang Wei , Gong Gaolang , Chen Chuansheng , Xue Gui , Dong Qi , Chen Chunhui 
Published: December 2023

Abstract
Imaging genetics studies with large samples have identified many genes associated with brain functions and structures, but little is known about genes associated with brain functional and structural network properties. The current genome-wide association study examined graph theory measures of brain structural and functional networks with 497 healthy Chinese participants (17–28 years). Four genes (TGFB3, LGI1, TSPAN18, and FAM155A) were identified to be significantly associated with functional network global efficiency, and two (NLRP6 and ICE2) with structural network global efficiency. Meta-analysis of structural and functional brain network property confirmed the four functional-related genes and revealed two more (RBFOX1 and WWOX). They were reported to be significantly associated with regional brain structural or functional measurements in the UK Biobank project; and showed differential gene expression level between low and high structure–function coupling regions according to Allen Human Brain Atlas gene expression data. Taken together, our results suggest that brain structural and functional networks had shared and unique genetic bases, consistent with the notion of many-to-many structure–function coupling of the brain.
Pre-train, Prompt, and Recommendation: A Comprehensive Survey of Language Modeling Paradigm Adaptations in Recommender Systems
Authors: Liu Peng , Zhang Lemei , Gulla Jon Atle 
Published: December 2023

Abstract
The emergence of Pre-trained Language Models (PLMs) has achieved tremendous success in the field of Natural Language Processing (NLP) by learning universal representations on large corpora in a self-supervised manner. The pre-trained models and the learned representations can be beneficial to a series of downstream NLP tasks. This training paradigm has recently been adapted to the recommendation domain and is considered a promising approach by both academia and industry. In this paper, we systematically investigate how to extract and transfer knowledge from pre-trained models learned by different PLM-related training paradigms to improve recommendation performance from various perspectives, such as generality, sparsity, efficiency and effectiveness. Specifically, we propose a comprehensive taxonomy to divide existing PLM-based recommender systems w.r.t. their training strategies and objectives. Then, we analyze and summarize the connection between PLM-based training paradigms and different input data types for recommender systems. Finally, we elaborate on open issues and future research directions in this vibrant field.
An Efficient Self-Supervised Cross-View Training For Sentence Embedding
Authors: Limkonchotiwat Peerat , Ponwitayarat Wuttikorn , Lowphansirikul Lalita , Udomcharoenchaikit Can , Chuangsuwanich Ekapol , Nutanong Sarana 
Published: December 2023

Abstract
Self-supervised sentence representation learning is the task of constructing an embedding space for sentences without relying on human annotation efforts. One straightforward approach is to finetune a pretrained language model (PLM) with a representation learning method such as contrastive learning. While this approach achieves impressive performance on larger PLMs, the performance rapidly degrades as the number of parameters decreases. In this paper, we propose a framework called Self-supervised Cross-View Training (SCT) to narrow the performance gap between large and small PLMs. To evaluate the effectiveness of SCT, we compare it to 5 baseline and state-of-the-art competitors on seven Semantic Textual Similarity (STS) benchmarks using 5 PLMs with the number of parameters ranging from 4M to 340M. The experimental results show that STC outperforms the competitors for PLMs with less than 100M parameters in 18 of 21 cases.1
Survival and moulting rates of larvae of Callinectes sapidus Rathbun, 1896 under different environmental circumstances (Brachyura, Portunidae)
Authors: Gencer Övgü 
Published: December 2023

Abstract
This study investigated the well-being and survival of larvae of the blue crab, Callinectes sapidus, under the influence of several abiotic and biotic factors, in order to collect relevant data for optimizing the larval period in the culture of this species. Aspects tested and examined were primarily: water volume, stocking density, salinity, (frequency of) moulting, starvation, mortality, cannibalism, behavioural aspects (e.g., mobility, intraspecific aggression), larval development, as well as the influence of ground colours. All aspects appeared to influence the duration and success of the larval period, from zoea-I to megalopa, but the main difference was observed to be related to the (water) volume of the culture tanks.
Spontaneous Activation of the Pacific Meridional Overturning Circulation (PMOC) in Long-Term Ocean Response to Greenhouse Forcing
Authors: Curtis Paul Edwin , Fedorov Alexey V. 
Published: December 2023

Abstract
The present-day deep ocean global meridional overturning circulation is dominated by the Atlantic meridional overturning circulation (AMOC), with dense water sinking in the high-latitude North Atlantic Ocean. In contrast, deep-water formation in the subarctic North Pacific is inhibited by a strong upper-ocean halocline, which prevents the development of an analogous Pacific meridional overturning circulation (PMOC). Nevertheless, paleoclimate evidence suggests that a PMOC with deep-water formation in the North Pacific was active, for instance, during the warm Pliocene epoch and possibly during the most recent deglaciation. In the present study, we describe a spontaneous activation of the PMOC in a multimillennial abrupt 4 × CO2 experiment using one of the configurations of the Community Earth System Model (CESM1). Soon after the imposed CO2 increase, the model’s AMOC collapses and remains in a weakened state for several thousand years. The PMOC emerges after some 2500 years of integration, persists for about 1000 years, reaching nearly 10 Sv (1 Sv ≡ 106 m3 s−1), but eventually declines to about 5 Sv. The PMOC decline follows the AMOC recovery in the model, consistent with an Atlantic–Pacific interbasin seesaw. The PMOC activation relies on two factors: (i) gradual warming and freshening of the North Pacific deep ocean, which reduces ocean vertical stratification on millennial time scales, and (ii) upper-ocean salinity increase in the subarctic North Pacific over several centuries, followed by a rapid erosion of the pycnocline and activation of deep-water formation. Ultimately, our results provide insights on the characteristics of global ocean overturning in warm climates.
Foreign Body Reaction Requiring Re-Exploration After Tympanoplasty With Porcine Small Intestinal Submucosa Reconstruction
Authors: Fullerton Zoe H. , Wei Eric X. , Green Allen , Sajjadi Hamed 
Published: December 2023

Objective: We present the first published case of large foreign body reaction to Biodesign (Cook Medical, Bloomington, IN), an acellular otologic graft matrix derived from porcine small intestinal submucosa, after use in tympanoplasty surgery in a patient without previous exposure to meat products. Methods: A single case report of a 39-year-old female who developed tinnitus, ear drainage, and large fibrotic mass in external auditory canal and extending into middle ear after Type I medial graft tympanoplasty with Biodesign Graft. Left endoscopic microdissection and resection of the tympanic membrane and middle ear fibrotic mass were performed. Main findings: Surgical excision of the fibrous mass required extensive microdissection to ensure preservation of the ossicles and chorda tympani. Postoperatively, hearing improved and otalgia and otorrhea resolved. Conclusions: We report the first case of post-tympanoplasty reaction with the use of Biodesign acellular porcine graft in a patient with no previous known exposure to meat products. Although this presentation appears to be rare, it reinforces the need for careful patient selection and counseling around the use of porcine or other foreign grafts.
Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation for patients with refractory out-of-hospital cardiac arrest: A retrospective propensity matching analysis
Authors: Sun Peng , Liu Wei , Li Mei , Zhang Lei , Liu Li-Na , Liu Zhan-Xiao , Wang Xu-Dong 
Published: December 2023

Objective The incidence of out-of-hospital cardiac arrest (OHCA) is high. Though extracorporeal cardiopulmonary resuscitation (ECPR) has been considered a potential treatment for refractory cardiac arrest after failure of conventional cardiopulmonary resuscitation (CCPR), the benefit of ECPR in refractory OHCA remains uncertain. Methods In this retrospective cohort study, we included patients with refractory OHCA who visited the Emergency Department of the Aerospace Center Hospital between January 2018 and April 2023. We divided the patients into the ECPR Group and the CCPR Group. The primary endpoint of the study was the neurological function of the patients in both groups 3 months after the cardiac arrest. We used propensity score matching to reduce selection bias and identified factors associated with good neurological function when OHCA was treated with ECPR by performing univariate and multivariate correlation analyses on surviving patients with good neurological function in the ECPR group. Results During the study period, we enrolled 133 patients, consisting of 33 in the ECPR group and 100 in the CCPR group. The survival rate of patients with good neurological function at discharge was 18.2% (6/33 cases) in the ECPR group and 9% (9/100 cases) in the CCPR group, p = .20. Three months after discharge, the survival rate of patients with good neurological function was 15.2% (5/33 cases) in the ECPR group and 8% (8/100 cases) in the CCPR group, p = .31. Using propensity score matching, we identified 22 pairs of patients for further analysis. Among these, 3 months after discharge, the survival rate of patients with good neurological function was 13.6% (3/22 cases) in the ECPR group and 4.5% (1/22 cases) in the CCPR group, p = .61, and the survival rate at discharge was 18.2% (4/22 cases) in the ECPR group and 4.5% (1/22 cases) in the CCPR group, p = .34. The univariate analysis of patients with good neurological function in the ECPR group showed that time without perfusion, hypoperfusion time, and PCI treatment were associated factors affecting the prognosis of neurological function in patients, while multivariate analysis showed that hypoperfusion time was independently associated with good neurological function, with an OR (95% CI) of 1.06 (1.00–1.14) and p = .05. Conclusion Our findings suggested that ECPR failed to significantly improve neurological outcome in patients with refractory OHCA; however, the small sample size in this study may be insufficient to detect clinically relevant differences. In addition, hypoperfusion time may be a key predictive factor in identifying candidates for ECPR.
Acceptance and Commitment Therapy is feasible for people with acquired brain injury: A process evaluation of the BrainACT treatment
Authors: Rauwenhoff Johanne CC , Bol Yvonne , Peeters Frenk , van Heugten Caroline M 
Published: December 2023

Objective To evaluate the feasibility of Acceptance and Commitment Therapy for people with acquired brain injury. Design A process evaluation of the BrainACT treatment was conducted alongside a randomised controlled trial. Setting Psychology departments of hospitals and rehabilitation centres. Subjects Tweny-seven participants with acquired brain injury and 11 therapists. Intervention BrainACT is an Acceptance and Commitment Therapy adapted for the needs and possible cognitive deficits of people with acquired brain injury, provided in eight one-hour face-to-face or video-conference sessions. Measurements The attendance and compliance rates, engagement, satisfaction, and perceived barriers and facilitators for delivery in clinical practice were investigated using semi-structured interviews with participants and therapists and therapy logs. Results 212 of the 216 sessions in total were attended and 534 of the 715 protocol elements across participants and sessions were delivered. Participants were motivated and engaged. Participants and therapists were satisfied with the intervention and participants reported to have implemented skills in their daily routines acquired during therapy. Key strengths are the structure provided with the bus of life metaphor, the experiential nature of the intervention, and the materials and homework. Participants and therapists often preferred face-to-face sessions, however, when needed video-conferencing is a good alternative. Conclusion BrainACT is a feasible intervention for people with anxiety and depressive symptoms following acquired brain injury. However, when the content of the intervention is too extensive, we recommend adding two extra sessions.
Clarification and Application of the Category Profit on Alienation
Authors: Duman Alper , Tonak E. Ahmet 
Published: December 2023

This article presents profit on alienation (POA) as one of the sources of profit in capitalist economies. In addition to identifying and situating POA among other profit flows, we have attempted to operationalize it in the real estate and finance sectors. In the empirical part of the article, we estimate POA in those sectors in Turkey for the period 2010–2019. The extent of estimated profits based on POA in those sectors is not insignificant. These findings confirm our position that utilizing POA in exploring capitalist dynamics would be a fruitful endeavor. JEL Classification: B3, B51, H27, G51
Long-term water aging of composites with bamboo fiber and montmorillonite filler
Authors: Chakkour Mouad , Moussa Mohamed Ould , Khay Ismail , Balli Mohamed , Ben Zineb Tarak 
Published: December 2023

This article examines the degradation mechanisms and mechanical properties of unfilled and montmorillonite-filled bamboo fiber-composites, under long-term water aging (up to 120 days) at room temperature. The main findings show that the water absorption and hydrolysis processes simultaneously occur during aging. The presence of clay fillers (3 wt %) reduces the water absorption content of composites from 18.69% to 15.68% after 120 aging days. However, their moisture absorption rate increases after adding particles. Scanning electron microscope images confirm the development of structural damage induced by the extra-swelling of particles, enabling more water absorption after long-term aging. Interestingly, the unfilled composites lose about 18.7% and 17.94% of their initial tensile strength and modulus after 120 aging days, which is attributed to the swelling/plasticization mechanisms and the chemical degradation at the interface, respectively. However, the tensile strength and modulus of montmorillonite-filled composites drop by 35.78% and 32.47%, respectively. This poor resilience to aging is attributed to the development of microstructural damage. The results of this work provide a clear insight into the long-term mechanical properties of composite materials and shed light on their systematic aging mechanisms, with a view to their application in harsh environments.
Bioinformatics Analyzes the Mechanisms of Codonopsis Radix in Treating Ovarian Cancer
Authors: Chen Zhenhui , Zhou Yan , Shen Yun , Ye Yanrong 
Published: December 2023

Background Codonopsis Radix (CR), a renowned traditional Chinese medicine (TCM) formula, has been widely applied for its immunomodulatory, antitumor, antioxidant, neuroprotective, and antiviral effects. However, the multitarget mechanism of CR in ovarian cancer (OC) remains to be elucidated. Objectives We applied bioinformatics and molecular docking techniques to explore possible pharmacological targets, bioactivities, and molecular mechanisms of CR for OC treatment. Materials and Methods We identified 40 common genes associated with CR and OC and obtained core genes through a protein–protein interaction network. Results Enrichment analysis revealed that mitochondrial electron transport was the key biological process involved. Based on the analysis, we selected estrogen receptor 1 (ESR1) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) as the key target genes for molecular docking. In the final verification analysis, we evaluated the effect of the PIK3CA mutation on the survival rate of patients with OC and determined that the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was the key pathway in the OC treatment. Conclusion These results suggest that CR inhibits the activity of mitochondrial complex II, reduces adenosine triphosphate (ATP) production by mitochondrial electron transport, inhibits PI3K/AKT phosphorylation, and promotes apoptosis in OC cells.