bluuebunny/crossref_metadata_2025_split huggingface dataset:
The BET inhibitor/degrader ARV-825 prolongs the growth arrest response to Fulvestrant + Palbociclib and suppresses proliferative recovery in ER-positive breast cancer
Authors: Finnegan Ryan M. , Elshazly Ahmed M. , Patel Nipa H. , Tyutyunyk-Massey Liliya , Tran Tammy H. , Kumarasamy Vishnu , Knudsen Erik S. , Gewirtz David A. 
Published: January 2023

Anti-estrogens or aromatase inhibitors in combination with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are the current standard of care for estrogen receptor-positive (ER+) Her-2 negative metastatic breast cancer. Although these combination therapies prolong progression-free survival compared to endocrine therapy alone, the growth-arrested state of residual tumor cells is clearly transient. Tumor cells that escape what might be considered a dormant or quiescent state and regain proliferative capacity often acquire resistance to further therapies. Our studies are based upon the observation that breast tumor cells arrested by Fulvestrant + Palbociclib enter into states of both autophagy and senescence from which a subpopulation ultimately escapes, potentially contributing to recurrent disease. Autophagy inhibition utilizing pharmacologic or genetic approaches only moderately enhanced the response to Fulvestrant + Palbociclib in ER+ MCF-7 breast tumor cells, slightly delaying proliferative recovery. In contrast, the BET inhibitor/degrader, ARV-825, prolonged the growth arrested state in both p53 wild type MCF-7 cells and p53 mutant T-47D cells and significantly delayed proliferative recovery. In addition, ARV-825 added after the Fulvestrant + Palbociclib combination promoted apoptosis and demonstrated efficacy in resistant RB deficient cell lines. These studies indicate that administration of BET inhibitors/degraders, which are currently being investigated in multiple clinical trials, may potentially improve standard of care therapy in metastatic ER+ breast cancer patients and may further prolong progression-free survival.
Deep learning-based prediction of deliverable adaptive plans for MR-guided adaptive radiotherapy: A feasibility study
Authors: Buchanan Laura , Hamdan Saleh , Zhang Ying , Chen Xinfeng , Li X. Allen 
Published: January 2023

PurposeFast and automated plan generation is desirable in radiation therapy (RT), in particular, for MR-guided online adaptive RT (MRgOART) or real-time (intrafractional) adaptive RT (MRgRART), to reduce replanning time. The purpose of this study is to investigate the feasibility of using deep learning to quickly predict deliverable adaptive plans based on a target dose distribution for MRgOART/MRgRART.MethodsA conditional generative adversarial network (cGAN) was trained to predict the MLC leaf sequence corresponding to a target dose distribution based on reference plan created prior to MRgOART using a 1.5T MR-Linac. The training dataset included 50 ground truth dose distributions and corresponding beam parameters (aperture shapes and weights) created during MRgOART for 10 pancreatic cancer patients (each with five fractions). The model input was the dose distribution from each individual beam and the output was the predicted corresponding field segments with specific shape and weight. Patient-based leave-one-out-cross-validation was employed and for each model trained, four (44 training beams) out of five fractionated plans of the left-out patient were set aside for testing purposes. We deliberately kept a single fractionated plan in the training dataset so that the model could learn to replan the patient based on a prior plan. The model performance was evaluated by calculating the gamma passing rate of the ground truth dose vs. the dose from the predicted adaptive plan and calculating max and mean dose metrics.ResultsThe average gamma passing rate (95%, 3mm/3%) among 10 test cases was 88%. In general, we observed 95% of the prescription dose to PTV achieved with an average 7.6% increase of max and mean dose, respectively, to OARs for predicted replans. Complete adaptive plans were predicted in ≤20 s using a GTX 1660TI GPU.ConclusionWe have proposed and demonstrated a deep learning method to generate adaptive plans automatically and rapidly for MRgOART. With further developments using large datasets and the inclusion of patient contours, the method may be implemented to accelerate MRgOART process or even to facilitate MRgRART.
Personalized antiplatelet therapy guided by clopidogrel pharmacogenomics in acute ischemic stroke and transient ischemic attack: A prospective, randomized controlled trial
Authors: Zhang Xiaoguang , Jiang Shanshan , Xue Jie , Ding Ying , Gu Jingyu , Hu Liang , Xu Xushen , Li Zhizhang , Kong Yuming , Li Youmei , Zhu Xiaoqiong , Yue Yunhua 
Published: January 2023

Background: Clopidogrel is frequently used in patients with ischemic stroke or transient ischemic attack (TIA), but its efficacy is hampered by inter-individual variability, due to genetic differences associated with clopidogrel metabolism. We conducted this randomized controlled trial to validate whether the personalized antiplatelet therapy based on clopidogrel pharmacogenomics and clinical characteristics leads to better clinical outcomes compared with standard treatment.Methods: Patients were randomly divided into the standard group or pharmacogenetic group, in which the pharmacogenetic group required the detection of the genotyping of CYP2C19*2, CYP2C19*3, and CYP2C19*17. Patients were followed up for 90 days for the primary efficacy endpoint of new stroke events, secondary efficacy endpoint of individual or composite outcomes of the new clinical vascular events, and the incidence of disability. The primary safety outcome was major bleeding.Results: A total of 650 patients underwent randomization, among which 325 were in the pharmacogenomics group while 325 were in the standard group. Our study found after a 90-day follow-up, the risk of stroke and composite vascular events in the pharmacogenomics group was lower than that in the standard group. The incidence of disability significantly decreased in the pharmacogenomics group. In addition, no statistically significant differences were observed in bleeding events between the two groups.Conclusion: The present study demonstrates that personalized antiplatelet therapy guided by clopidogrel pharmacogenomics and clinical characteristics can significantly improve the net clinical benefit of ischemic stroke or TIA patients during the 90-day treatment period without increasing bleeding risk.
Single and composite damage mechanisms of soil polyethylene/polyvinyl chloride microplastics to the photosynthetic performance of soybean (Glycine max [L.] merr.)
Authors: Li Haibin , Song Fupeng , Song Xiliang , Zhu Kongming , Lin Qun , Zhang Jinliang , Ning Guoqiang 
Published: January 2023

IntroductionAdverse impacts of soil microplastics (MPs, diameter&lt;5 mm) on vegetative growth and crop production have been widely reported, however, the single and composite damage mechanisms of polyethylene (PE) /polyvinyl chloride (PVC) microplastics (MPs) induced photosynthesis inhibition are still rarely known.MethodsIn this study, two widely distributed MPs, PE and PVC, were added to soils at a dose of 7% (dry soil) to examine the single and composite effects of PE-MPs and PVC-MPs on the photosynthetic performance of soybean.ResultsResults showed PE-MPs, PVC-MPs and the combination of these two contaminants increased malondialdehyde (MDA) content by 21.8-97.9%, while decreased net photosynthesis rate (Pn) by 11.5-22.4% compared to those in non-stressed plants, PVC MPs caused the most severe oxidative stress, while MPs stress resulted in Pn reduction caused by non-stomatal restriction. The reason for this is the single and composite MPs stress resulted in a 6% to 23% reduction in soybean PSII activity RCs reaction centers, along with negative effects on soybean PSII energy uptake, capture, transport, and dissipation. The presence of K-band and L-band also represents an imbalance in the number of electrons on the donor and acceptor side of PSII and a decrease in PSII energy transfer. Similarly, PVC single stress caused greater effects on soybean chloroplast PSII than PE single stress and combined stresses.DiscussionPE and PVC microplastic stress led to oxidative stress in soybean, which affected the structure and function of photosynthetic PSII in soybean, ultimately leading to a decrease in net photosynthetic rate in soybean.
RNA-Seq reveals the key pathways and genes involved in the light-regulated flavonoids biosynthesis in mango (Mangifera indica L.) peel
Authors: Qian Minjie , Wu Hongxia , Yang Chengkun , Zhu Wencan , Shi Bin , Zheng Bin , Wang Songbiao , Zhou Kaibing , Gao Aiping 
Published: January 2023

IntroductionFlavonoids are important water soluble secondary metabolites in plants, and light is one of the most essential environmental factors regulating flavonoids biosynthesis. In the previous study, we found bagging treatment significantly inhibited the accumulation of flavonols and anthocyanins but promoted the proanthocyanidins accumulation in the fruit peel of mango (Mangifera indica L.) cultivar ‘Sensation’, while the relevant molecular mechanism is still unknown.MethodsIn this study, RNA-seq was conducted to identify the key pathways and genes involved in the light-regulated flavonoids biosynthesis in mango peel.ResultsBy weighted gene co-expression network analysis (WGCNA), 16 flavonoids biosynthetic genes were crucial for different flavonoids compositions biosynthesis under bagging treatment in mango. The higher expression level of LAR (mango026327) in bagged samples might be the reason why light inhibits proanthocyanidins accumulation in mango peel. The reported MYB positively regulating anthocyanins biosynthesis in mango, MiMYB1, has also been identified by WGCNA in this study. Apart from MYB and bHLH, ERF, WRKY and bZIP were the three most important transcription factors (TFs) involved in the light-regulated flavonoids biosynthesis in mango, with both activators and repressors. Surprisingly, two HY5 transcripts, which are usually induced by light, showed higher expression level in bagged samples.DiscussionOur results provide new insights of the regulatory effect of light on the flavonoids biosynthesis in mango fruit peel.
Predictors of everyday functional impairment in older patients with schizophrenia: A cross-sectional study
Authors: Wu Chenxin , Ye Junrong , Li Shaohua , Wu Jialan , Wang Chen , Yuan Lexin , Wang Haoyun , Pan Yuanxin , Huang Xingxiao , Zhong Xiaomei , Huang Meilian , Guo Jianxiong , Ning Yuping , Xiao Aixiang 
Published: January 2023

ObjectiveThis study investigates the prevalence of everyday functional impairment among older adults with schizophrenia and builds a predictive model of functional decline.MethodsA total of 113 hospitalized older patients enrolled in this study. Functional impairment is defined according to the Functional Activities Questionnaire (FAQ). Patients who scored &lt;9 could function independently daily, while those who scored ≥9 had problems in everyday functional activities. Data collected include sociodemographic characteristics, depressive symptoms, social support, and physical comorbidities, which were classified according to the eight anatomical systems of the human body.ResultsThe sample comprised 75% female participants with a mean age of 63.74 ± 7.42 years old. A total of 33.6% had a functional impairment, while cognitive impairment was present in 63.7%. Independent participants had better urinary system and respiratory system health (P &lt; 0.05). After adjusting for the potential confounders of age, disease course, physical comorbidities, psychiatric symptoms, the ability to independently carry out daily activities, and cognitive function, we found that impaired everyday function is associated with poor cognition, depressive symptoms, first admission, psychiatric symptoms (especially positive symptoms), ADL, and respiratory and urinary system diseases.ConclusionEveryday functional capacity is predicted by disease course, admission time, cognition, depressive symptoms, severity of psychosis, ability to carry out daily activities, and respiratory and urinary system health status. Urinary system diseases contribute significantly to the prediction of impaired function. Future studies should focus on health status, drug use, and everyday functional recovery in older patients with schizophrenia.
Plerixafor and granulocyte colony stimulating factor for poor mobilizers in patients undergoing autologous peripheral hematopoietic stem cell transplantation: Single institution study
Authors: El Cheikh Jean , Terro Khodr , El Warrak Samantha , Ghaoui Nohra , Sharrouf Layal , Timonian Michael Anthony , Ismail Fatima , Zahreddine Ammar , Kreidieh Nabila , Moukalled Nour , Abou Dalle Iman , Bazarbachi Ali 
Published: January 2023

BackgroundAutologous hematopoietic stem cell transplantation (ASCT) has become the mainstay treatment for many hematological malignancies and solid tumors. An adequate number of stem cells must be collected for better ASCT outcomes, which is challenging in 5%–30% of patients. To improve mobilization, plerixafor is used along with granulocyte colony-stimulating factor (G-CSF).Patients and methodsWe conducted a retrospective single center study involving patients who received plerixafor pre-ASCTs between January 2013 and December 2020 at a tertiary care center in Lebanon. We identified a total of 84 consecutive adult patients. All patients identified were poor mobilizers and have eventually received plerixafor either as pre-emptive use before first apheresis in those with peripheral CD34 + of less than 20 cells/ul, or after failure of first apheresis in those with peripheral stem cells (PSC) &gt;2.0 × 106 cells/Kg.ResultsThe median age at ASCT was 52.7 years (22–74) with 61% male predominance. Multiple myeloma was the most prevalent disease 64% followed by Lymphoma 32%. The majority of patients were in complete remission 64% at the time of ASCT. Most patients received proteasome inhibitor-based induction therapy 67% and Melphalan-based conditioning therapy 68%. The median follow-up from ASCT was 9 months (1–59). It was noted that greater body mass index (BMI) is a significant factor for better PSC collection whether premobilization (P = 0.003), or post plerixafor mobilization (P = 0.024). Moreover, Multiple Myeloma patients showed better mobilization using Plerixafor (P = 0.049). Using Plerixafor along with G-CSF in poor mobilizers post G-CSF alone showed a statistically significant increase in the collected PSC mean from 0.67 × 106 cells/Kg to 4.90 × 106 cells/Kg (P &lt; 0.001) with a failure rate only for 12 patients (15%). The infusion of PSC &gt; 2.5 × 106 cells/Kg has shown 3 days decrease in time to platelet engraftment (P = 0.021) and a 36% decrease in progression/relapse rate (P = 0.025).ConclusionPlerixafor is effective in increasing the PSC yield in poor mobilizers. Low BMI and hematologic malignancies other than Multiple Myeloma are risk factors for poor mobilization. More studies should be performed to establish more risk factors, helping us to identify poor mobilizers more accurately and initiate plerixafor mobilization early on.
Effect of acute ankle experimental pain on lower limb motor control assessed by the modified star excursion balance test
Authors: Bertrand-Charette Michaël , Roy Jean-Sébastien , Bouyer Laurent J. 
Published: January 2023

IntroductionFollowing most musculoskeletal injuries, motor control is often altered. Acute pain has been identified as a potential contributing factor. However, there is little evidence of this interaction for acute pain following ankle sprains. As pain is generally present following this type of injury, it would be important to study the impact of acute pain on ankle motor control. To do so, a valid and reliable motor control test frequently used in clinical settings should be used. Therefore, the objective of this study was therefore to assess the effect of acute ankle pain on the modified Star Excursion Balance Test reach distance.MethodsUsing a cross-sectional design, 48 healthy participants completed the modified Star Excursion Balance Test twice (mSEBT1 and mSEBT2). Following the first assessment, they were randomly assigned to one of three experimental groups: Control (no stimulation), Painless (non-nociceptive stimulation) and Painful (nociceptive stimulation). Electrodes were placed on the right lateral malleolus to deliver an electrical stimulation during the second assessment for the Painful and Painless groups. A generalized estimating equations model was used to compare the reach distance between the groups/conditions and assessments.ResultsPost-hoc test results: anterior (7.06 ± 1.54%; p &lt; 0.0001) and posteromedial (6.53 ± 1.66%; p &lt; 0.001) directions showed a significant reach distance reduction when compared to baseline values only for the Painful group. Regarding the anterior direction, this reduction was larger than the minimal detectable change (5.87%).ConclusionThe presence of acute pain during the modified Star Excursion Balance Test can affect performance and thus might interfere with the participant's lower limb motor control. As none of the participants had actual musculoskeletal injury, this suggests that pain and not only musculoskeletal impairments could contribute to the acute alteration in motor control.
Case report of retroperitoneal ectopic pancreas with adrenal adenoma
Authors: Sun Zhaochen , Chen Tao , Zhu Xuefeng , Geng Jie , Sui Chaofan , Zhang Nan , Guo Lingfei 
Published: January 2023

BackgroundEctopic pancreas is a congenital anomaly in which pancreatic tissue is anatomically separated from the main gland and without vascular or ductal continuity. A case of retroperitoneal ectopic pancreas with adrenal adenoma has never yet been reported.Case PresentationA 54-year-old man presented three masses in the left retroperitoneum, and two of them were resected. The pathologic findings were a retroperitoneal ectopic pancreas with adrenal adenoma.ConclusionWe report an extremely rare case of a retroperitoneal ectopic pancreas and its characterization with dynamic gadolinium-enhanced magnetic resonance imaging (MRI).
Specificities of Meningitis and Meningo-Encephalitis After Kidney Transplantation: A French Retrospective Cohort Study
Authors: Tamzali Y. , Scemla A. , Bonduelle T. , Garandeau C. , Gilbert M. , Randhawa S. , De Nattes T. , Hachad H. , Pourcher V. , Taupin P. , Kaminski H. , Hazzan M. , Moal V. , Matignon M. , Fihman V. , Levi C. , Le Quintrec M. , Chemouny J. M. , Rondeau E. , Bertrand D. , Thervet E. , Tezenas Du Montcel S. , Savoye E. , Barrou B. , Kamar N. , Tourret J. 
Published: January 2023

Kidney transplant recipients develop atypical infections in their epidemiology, presentation and outcome. Among these, meningitis and meningoencephalitis require urgent and adapted anti-infectious therapy, but published data is scarce in KTRs. The aim of this study was to describe their epidemiology, presentation and outcome, in order to improve their diagnostic and management. We performed a retrospective, multicentric cohort study in 15 French hospitals that included all 199 cases of M/ME in KTRs between 2007 and 2018 (0.9 case per 1,000 KTRs annually). Epidemiology was different from that in the general population: 20% were due to Cryptococcus neoformans, 13.5% to varicella-zoster virus, 5.5% to Mycobacterium tuberculosis, and 4.5% to Enterobacteria (half of which produced extended spectrum beta-lactamases), and 5% were Post Transplant Lymphoproliferative Disorders. Microorganisms causing M/ME in the general population were infrequent (2%, for Streptococcus pneumoniae) or absent (Neisseria meningitidis). M/ME caused by Enterobacteria, Staphylococci or filamentous fungi were associated with high and early mortality (50%–70% at 1 year). Graft survival was not associated with the etiology of M/ME, nor was impacted by immunosuppression reduction. Based on these results, we suggest international studies to adapt guidelines in order to improve the diagnosis and the probabilistic treatment of M/ME in SOTRs.
On the Hermeneutics of Berio's “Sinfonia”
Authors: Акопян Левон Оганесович 
Published: January 2023

Вокально-оркестровая «Симфония» Лучано Берио (1968-1969) — своеобразный конгломерат идей, занимавших умы западных интеллектуалов в эпоху, когда начался подъем мультикультурализма, культ новизны постепенно сдавал свои позиции под натиском эстетического плюрализма, высокое искусство так или иначе вращалось вокруг тем экзистенциального одиночества и отчаяния, потерянности во враждебном мире, — тогда как научная мысль, даже в гуманитарных областях, стремилась к строгой структурированности, а в политической ориентации возобладал левый либерализм, не без симпатий к коммунизму. Богатое музыкальное и идейное содержание «Симфонии» вызвало к жизни обширную литературу герменевтической направленности. Вместе с тем в «Симфонии» обнаруживаются и такие глубинные универсальные смыслы, которые все еще во многом скрыты от поверхностного взгляда. Осуществленный в статье анализ музыкального и литературного содержания «Симфонии» направлен на истолкование этих смыслов. Привлеченный для этой цели ассоциативный контекст содержит данные из области антропологии, религии, философии, литературы и кино, не принятые во внимание в предшествующих исследованиях.
Luciano Berio's vocal-orchestral “Sinfonia” (1968-1969) represents a peculiar “symphony” of ideas that occupied the minds of Western intellectuals during the late sixties, when multiculturalism began to rise, the cult of novelty was gradually yielding its position under the pressure of aesthetic pluralism, serious literature and arts were concerned especially with the topics of existential solitude and despair, of being lost in a hostile world, while the scholarly thought, even in humanities, tended towards highly ordered structures, and the intellectual community's political orientation was predominantly leftist, not without sympathy with communism. The work's rich musical and ideological content gave rise to an extensive literature of hermeneutic orientation. At the same time, “Sinfonia” contains some deeper universal meanings, which are still largely hidden from a superficial view. The analysis of the work's musical and literary content, carried out in this article, is directed to a hermeneutic interpretation of these meanings. The present study's associative context includes data from the fields of anthropology, religion, philosophy, literature, and cinema, which, to the best of the author's knowledge, have not been taken into account in previous analytical writings.
Studying the Phenomenon of Operatic Madness. The Problem of Periodization
Authors: Любимов Дмитрий Вадимович 
Published: January 2023

В статье рассматривается проблема периодизации сцен безумия в европейском музыкальном театре. Автор анализирует три взгляда на историческую эволюцию оперного сумасшествия: психиатра Нила Бренера, культуролога Кортни Миллер и литературоведа Эстер Хузер. Все названные ученые обсуждают исключительно тексты либретто, не касаясь их музыкального воплощения. Изложены основные критерии и принципы данных периодизаций, обозначены хронологические рамки периодов, описаны их характерные особенности. Отмечены как методологически перспективные, так и весьма спорные стороны рассматриваемых работ. Цитаты из исследований представлены в авторском переводе.
The article deals with the problem of the periodization of madness scenes in European musical theater. The author analyzes three views on the historical evolution of opera madness: by psychiatrist Neil Brener, by cultural critic Courtney Miller and by literary scholar Esther Huzer. All these scholars discuss only the texts of the librettos without touching on their musical embodiment. The main criteria and principles of each periodization are exposed, the chronological framework of the periods is outlined, and their characteristic features are described. Both methodologically promising and highly controversial aspects of the works under consideration are emphasized. Quotations from the research are presented in the author's translation.