bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Autoimmune Pemphigus Vulgaris in a Patient Treated With Cemiplimab for Multiple Locally Advanced Cutaneous Squamous Cell Carcinoma
Authors: Buquicchio Rosalba , Mastrandrea Valentina , Strippoli Sabino , Quaresmini Davide , Guida Michele , Filotico Raffaele 
Published: August 2021

BackgroundPemphigus vulgaris (PV) is a rare and severe autoimmune blistering disorder affecting the skin and mucous membranes, characterized by the production of autoantibodies against two desmosomal adhesion proteins, desmoglein 1 and 3. In patients with advanced squamous cell carcinoma of the skin unfit for surgery and radiotherapy, immune check-point inhibitors, including the anti-Programmed Death-1 (PD-1) agent cemiplimab have been successfully employed proving relevant clinical outcomes. Cemiplimab is a monoclonal antibody capable of inhibiting PD-1 signalling that has recently been approved for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinoma. Although the peculiar setting of advanced CSCC involving elderly patients, rare and unusual skin immune-related adverse events such as PV could be observed in cemiplimab treated patients.Case ReportA 95-year-old man without a history of autoimmune disease was treated with cemiplimab for multiple and advanced squamous cell carcinomas of the head obtaining a complete response to therapy. After seven cycles of cemiplimab administered every 21 days, the patient developed a mucocutaneous blistering eruption. Clinical diagnosis of PV was suspected on the basis of the diffuse involvement of trunk and extremities with large blisters and necrotic eschar. It was carried out an ELISA test, that showed high level of circulating antibodies against desmoglein 1, thus confirming the diagnosis of PV. For this reason, cemiplimab infusion was discontinued and complete resolution of skin lesions was obtained using oral prednisone 0,8 mg/kg/daily for four weeks. Once remission was achieved, a maintenance dose of 10 mg/day was administered, observing a good control of bullous disease and low value of desmoglein 1. Response to CSCC persisted also during cemiplimab discontinuation, until obtaining a complete remission still persisting at 9 months after the last cycle of therapy.ConclusionThe case we observed is the first description of PV revealed from cemiplimab therapy, thus suggesting that cemiplimab could allow the arise of underlying autoimmune PV, through a mechanism both T and B-cell-mediated.
Prognostic Relevance of 18F-FDG-PET/CT-Guided Target Volume Delineation in Loco-Regionally Advanced Nasopharyngeal Carcinomas: A Comparative Study
Authors: Yan Ouying , Wang Hui , Han Yaqian , Fu Shengnan , Chen Yanzhu , Liu Feng 
Published: August 2021

IntroductionAn optimal approach to define tumor volume in locoregionally advanced nasopharyngeal carcinoma (NPC) using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) remains unclear. This retrospective study aimed at comparing the outcomes and toxicities of different FDG-PET/CT-guided techniques for primary tumor volume delineation in locoregionally advanced NPC.MethodsFrom August 2015 to February 2018, 292 patients with stage III-IVB NPC received FDG-PET/CT-guided IMRT. Three PET/CT-based techniques were used to determine the gross tumor volume (GTV) as follows: visual criteria (group A; n = 98), a standard uptake value (SUV) threshold of 2.5 (group B; n = 95), and a threshold of 50% maximal intensity (group C, n = 99) combined with a dose-painting technique.ResultsIn groups A, B, and C, the 5-year LRFS rates were 89.4%, 90.0%, and 97.8%, respectively (p = 0.043). The 5-year DMFS rates were 75.1%, 76.0%, and 87.7%, respectively (p = 0.043). The 5-year DFS rates were 70.9%, 70.3%, and 82.2%, respectively (p = 0.048). The 5-year OS rates were 73.5%, 73.9%, and 84.9%, respectively (p = 0.038). Group C showed significantly higher 5-year LRFS, LRRFS, DMFS, DFS, and OS than those in groups A and B (p &lt; 0.05). No statistically significant differences were observed between the three study groups in the cumulative incidences of grade 3-4 acute and late toxicities. Multivariate analyses showed that the PET/CT-guided technique for target volume delineation was an independent prognostic factor for 5-year LRFS, DFS, DMFS, and OS (p = 0.039, p = 0.030, p = 0.035 and p = 0.028, respectively), and was marginally significant in predicting LRRFS (p = 0.080).ConclusionsThe 50% SUVmax threshold regimen for GTV delineation with dose-painting appeared to be superior to the visual criteria or SUV2.5 threshold in locoregionally advanced NPC, and there was no increased toxicity.
N6-Methyladenosine Writer Gene ZC3H13 Predicts Immune Phenotype and Therapeutic Opportunities in Kidney Renal Clear Cell Carcinoma
Authors: Guo Tao , Duan Hongxiang , Chen Jinbo , Liu Jinhui , Othmane Belaydi , Hu Jiao , Li Huihuang , Zu Xiongbing 
Published: August 2021

BackgroundAlthough the RNA modification N6-methyladenosine ZC3H13 has been found to play vital regulatory roles in many types of cancers, its role in predicting the tumor immune microenvironment (TME) and response to immune checkpoint blockade (ICB) in kidney renal clear cell carcinoma (KIRC) remains unclear.MethodsWe comprehensively analyzed the expression, prognostic significance and immunological role of ZC3H13 in pan-cancers and systematically correlated ZC3H13 with TME cell-infiltration, ICB response and targeted therapy in KIRC. The data were collected from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), Broad Institute Cancer Cell Line Encyclopedia (CCLE) and DrugBank database. Also, we performed RNA sequencing (RNA-seq) of 46 renal cell carcinoma tissues and 11 adjacent normal tissues to validate our result. All analyses were implemented using R software, version 3.6.3.ResultsZC3H13 was significantly differentially expressed in most tumors. However, its expression profiles and prognostic significance were consistent only in KIRC, regardless of overall survival, progression-free survival and cancer-specific survival. Additionally, ZC3H13 expression was correlated with clinicopathological factors in KIRC. Furthermore, we found that ZC3H13 might shape a noninflamed phenotype and could predict a lower response to ICB in KIRC. These results could be validated in our own RNA-seq data. Tumor mutation burden (TMB) was significantly higher in the low ZC3H13 group. Finally, we found that ZC3H13 could predict the sensitivity of targeted therapy for KIRC.ConclusionsZC3H13 might shape a noninflamed phenotype in KIRC. Moreover, ZC3H13 could predict the prognosis and clinical response of ICB and the sensitivity to targeted therapies in KIRC.
Clinical Characteristics and Outcomes Until 2 Years of Age in Preterm Infants With Typical Chest Imaging Findings of Bronchopulmonary Dysplasia: A Propensity Score Analysis
Authors: Ruan Qiqi , Wang Jianhui , Shi Yuan 
Published: August 2021

Objective: The goal of the current study was to assess the associations of typical chest imaging findings of bronchopulmonary dysplasia (BPD) in preterm infants with clinical characteristics and outcomes until 2 years of age.Method: This retrospective cohort study enrolled 256 preterm infants with BPD who were admitted between 2014 and 2018. A propensity score analysis was used to adjust for confounding factors. The primary outcomes were the severity of BPD, home oxygen therapy (HOT) at discharge and mortality between 28 days after birth and 2 years of age. A multivariate logistic regression analysis was performed to identify related variables of mortality.Results: Seventy-eight patients with typical chest imaging findings were enrolled, of which 50 (64.1%) were first found by CXR, while 28 (35.9%) were first found by CT. In addition, 85.9% (67/78) were discovered before 36 weeks postmenstrual age (PMA) (gestational age [GA] &lt; 32 weeks) or before 56 days after birth (GA &gt; 32 weeks). After propensity score matching, the matched groups consisted of 58 pairs of patients. Those with typical imaging findings had a remarkably higher mortality rate (29.3 vs. 12.1%, p = 0.022, OR 3.021), higher proportion of severe BPD (32.8 vs. 12.1%, p = 0.003, OR 4.669) and higher rate of HOT at discharge (74.1 vs. 46.6%, p = 0.002, OR 3.291) than those without typical imaging findings. The multivariate logistic regression analysis showed that typical imaging findings ≤ 7 days and typical typical imaging findings &gt;7 days were independent risk factors for mortality in preterm infants with BPD (OR 7.794, p = 0.004; OR 4.533, p = 0.001).Conclusions: More attention should be given to chest imaging findings of BPD, especially in the early stage (within 7 days). Early recognition of the development of BPD helps early individualized treatment of BPD.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04163822.
Extracellular HSP90α Interacts With ER Stress to Promote Fibroblasts Activation Through PI3K/AKT Pathway in Pulmonary Fibrosis
Authors: Zhang Jinming , Zhong Wenshan , Liu Yuanyuan , Chen Weimou , Lu Ye , Zeng Zhaojin , Qiao Yujie , Huang Haohua , Wan Xuan , Li Wei , Meng Xiaojing , Zou Fei , Cai Shaoxi , Dong Hangming 
Published: August 2021

Pulmonary fibrosis is characterized by alveolar epithelial cell injury, lung fibroblast proliferation, differentiation, and extracellular matrix (ECM) deposition. Our previous study indicated that extracellular HSP90α (eHSP90α) promotes pulmonary fibrosis by activating the MAPK signaling pathway. Thus, treatment with 1G6-D7 (a selective HSP90α monoclonal antibody) to antagonize eHSP90α could effectively ameliorate fibrosis. This study aimed to elucidate the mechanism underlying the effects of eHSP90α in pulmonary fibrosis by focusing on its link with endoplasmic reticulum (ER) stress. Our results showed that eHSP90α promoted lung fibroblast differentiation by activating ER stress. Treatment with the ER stress inhibitor tauroursodeoxycholate (TUDCA) or glucose-regulated protein 78 kDa (GRP78) depletion significantly abrogated the effect of eHSP90α on ER stress and fibroblast activation. In addition, eHSP90α induced ER stress in fibroblasts via the phosphoinositide-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, which could be blocked by the PI3K/AKT inhibitor LY294002, and blockade of eHSP90α by 1G6-D7 markedly inhibited ER stress in the model, indicating preventive and therapeutic applications. Intriguingly, we observed that TUDCA effectively reduced the secretion of eHSP90α in vitro and in vivo. In conclusion, this study shows that the interaction between eHSP90α and ER stress plays a crucial role in pulmonary fibrosis, indicating a positive feedback in lung fibroblasts. Targeting eHSP90α and alleviating fibroblast ER stress may be promising therapeutic approaches for pulmonary fibrosis.
ACNPD: The Database for Elucidating the Relationships Between Natural Products, Compounds, Molecular Mechanisms, and Cancer Types
Authors: Tan Xiaojie , Fu Jiahui , Yuan Zhaoxin , Zhu Lingjuan , Fu Leilei 
Published: August 2021

Objectives: Cancer is well-known as a collection of diseases of uncontrolled proliferation of cells caused by mutated genes which are generated by external or internal factors. As the mechanisms of cancer have been constantly revealed, including cell cycle, proliferation, apoptosis and so on, a series of new emerging anti-cancer drugs acting on each stage have also been developed. It is worth noting that natural products are one of the important sources for the development of anti-cancer drugs. To the best of our knowledge, there is not any database summarizing the relationships between natural products, compounds, molecular mechanisms, and cancer types.Materials and methods: Based upon published literatures and other sources, we have constructed an anti-cancer natural product database (ACNPD) (http://www.acnpd-fu.com/). The database currently contains 521 compounds, which specifically refer to natural compounds derived from traditional Chinese medicine plants (derivatives are not considered herein). And, it includes 1,593 molecular mechanisms/signaling pathways, covering 10 common cancer types, such as breast cancer, lung cancer and cervical cancer.Results: Integrating existing data sources, we have obtained a large amount of information on natural anti-cancer products, including herbal sources, regulatory targets and signaling pathways. ACNPD is a valuable online resource that illustrates the complex pharmacological relationship between natural products and human cancers.Conclusion: In summary, ACNPD is crucial for better understanding of the relationships between traditional Chinese medicine (TCM) and cancer, which is not only conducive to expand the influence of TCM, but help to find more new anti-cancer drugs in the future.
The Immunostimulatory Effects of Commercial Feed Additives on Growth Performance, Non-specific Immune Response, Antioxidants Assay, and Intestinal Morphometry of Nile tilapia, Oreochromis niloticus
Authors: Kord Mohamed Ibrahim , Srour Tarek Mohamed , Omar Eglal Ali , Farag Ahmed Awny , Nour Abdel Aziz Moussa , Khalil Hala Saber 
Published: August 2021

Graphical AbstractThe immunostimulatory effects of commercial feed additives on growth performance, non-specific immune response, antioxidants assay, and intestinal morphometry of Nile tilapia, O. niloticus.
The Mediating Role of Loneliness Between Social Support and Depressive Symptoms Among Chinese Rural Adolescents During COVID-19 Outbreak: A Comparative Study Between Left-Behind and Non-left-behind Students
Authors: Hou Tianya , Xie Yawei , Mao Xiaofei , Liu Ying , Zhang Jianguo , Wen Jing , Chen Yan , Luo Zhechao , Cai Wenpeng 
Published: August 2021

Introduction: The COVID-19 pandemic has greatly impacted people's life across the globe. In a public health crisis, rural adolescents are more prone to mental health problems. The current study aimed to investigate the prevalence of depressive symptoms among Chinese rural adolescents during the COVID-19 outbreak, and examine the association between perceived social support and depressive symptoms and its underlying mechanisms.Method: Perceived Social Support Scale, UCLA Loneliness Scale, Patient Health Questionnaire-9 were administrated to 826 rural adolescents from Anhui Province, China, amid the COVID-19 crisis. Mackinnon's four-step procedure was employed to examine the mediating effect, while Hayes PROCESS macro was utilized to test the moderated mediation model.Results: The results showed the rate of depressive symptoms among rural adolescents in China was 77.6% during the outbreak of COVID-19. Female left-behind students and non-left-behind students from disrupted families experienced more depressive symptoms (all P &lt; 0.05). Loneliness mediated the association between perceive social support and depressive symptoms and the indirect effect was stronger in left-behind adolescents in comparison to non-left-behind adolescents during the COVID-19 pandemic.Conclusion: Depressive symptoms are extremely prevalent among Chinese rural adolescents during the COVID-19 outbreak, and perceived social support plays a protective role against depressive symptoms. Chinese rural adolescents, especially left-behind students, could benefit from the interventions aimed at enhancing the perceived social support and reducing loneliness during the COVID-19 pandemic.
Enhanced Expression of Thaumatin-like Protein Gene (LeTLP1) Endows Resistance to Trichoderma atroviride in Lentinula edodes
Authors: Ma Xiaolong , Fan Xiaolin , Wang Gangzheng , Xu Ruiping , Yan Lianlian , Zhou Yan , Gong Yuhua , Xiao Yang , Bian Yinbing 
Published: August 2021

Lentinula edodes (shiitake mushrooms) is heavily affected by the infection of Trichoderma atroviride, causing yield loss and decreases quality in shiitake mushrooms. The selection and breeding of fungal-resistant L. edodes species are an important approach to protecting L. edodes from T. atroviride infection. Herein, a highly resistant L. edodes strain (Y3334) and a susceptible strain (Y55) were obtained by using a resistance evaluation test. Transcriptome analyses and qRT-PCR detection showed that the expression level of LeTLP1 (LE01Gene05009) was strongly induced in response to T. atroviride infection in the resistant Y3334. Then, LeTLP1-silenced and LeTLP1-overexpression transformants were obtained. Overexpression of LeTLP1 resulted in resistance to T. atroviride. Compared with the parent strain Y3334, LeTLP1-silenced transformants had reduced resistance relative to T. atroviride. Additionally, the LeTLP1 protein (Y3334) exhibited significant antifungal activity against T. atroviride. These findings suggest that overexpression of LeTLP1 is a major mechanism for the resistance of L. edodes to T. atroviride. The molecular basis provides a theoretical basis for the breeding of resistant L. edodes strains and can eventually contribute to the mushroom cultivation industry and human health.
Metabolism of Diterpenoids Derived from the Bark of Cinnamomum cassia in Human Liver Microsomes
Authors: Choi Su Min , Pham Van Cong , Lee Sangkyu , Kim Jeong Ah 
Published: August 2021

Cinnamomum cassia L. is used as a spice and flavoring agent as well as a traditional medicine worldwide. Diterpenoids, a class of compounds present in C. cassia, have various pharmacological effects, such as anti-inflammatory, antitumor, and antibacterial activities; however, there are insufficient studies on the metabolism of diterpenoids. In this study, the metabolism of seven diterpenoids, namely, anhydrocinnzeylanol, anhydrocinnzeylanine (AHC), cinncassiol A, cinncassiol B, cinnzeylanol, cinnzeylanone, and cinnzeylanine, obtained from the bark of C. cassia was studied in human liver microsomes (HLMs). All studied diterpenoids, except for AHC, exhibited strong metabolic stability; however, AHC was rapidly metabolized to 3% in HLMs in the presence of β-NADPH. Using a high-resolution quadrupole-orbitrap mass spectrometer, 20 metabolites were identified as dehydrogenated metabolites (M1–M3), dehydrogenated and oxidated metabolites (M4–M10), mono-oxidated metabolites (M11–M13), or dioxidated metabolites (M14–M20). In addition, CYP isoforms involved in AHC metabolism were determined by profiling metabolites produced after incubation in 11 recombinant cDNA-expressed CYP isoforms. Thus, the diterpenoid compound AHC was identified in a metabolic pathway involving CYP3A4 in HLMs.
Necesidad de los sacramentos en este tiempo de pandemia
Authors: Buendía César 
Published: August 2021

Este artículo establece un diálogo entre la tradición de diferentes Padres de la Iglesia, la enseñanza doctrinal de los sacramentos y la coyuntura actual de la pandemia. Ante una situación tan adversa para los rituales y prácticas públicas de fe, el autor considera necesario volver sobre la dimensión de aquel milagro en el mundo moderno que representan los sacramentos, en especial la eucaristía y la confesión. Abordará también la perspectiva del ateísmo y la postura protestante, además de la superación que en torno de ellas ha marcado históricamente la doctrina de la Iglesia en materia sacramental. La reflexión sobre la gracia y los sacramentos también tendrá un lugar importante en estas páginas con el fin de alentarnos a la búsqueda de estos dones que en tiempos tan difíciles se topan ante restricciones desalentadoras.
Cuentos de casa de Diego Rondón Almuelle: la ilustración como categoría artística
Authors: Asencios Víctor Hugo 
Published: August 2021

El presente trabajo es un análisis desde la perspectiva de la historia del arte del libro álbum titulado Cuentos de casa realizado por el artista arequipeño Diego Rondón Almuelle, quien es uno de los más importantes artistas gráficos de inicios del siglo XXI. Formó parte del grupo Pandemia, un colectivo de artistas gráficos de la ciudad de Arequipa que realizaron publicaciones que circularon en Lima durante los primeros años de la década del 2000. Este trabajo se enlaza a un análisis previo de la obra de Rondón titulado La fantasía tenebrosa en la novela gráfica de Diego Rondón Almuelle (2014) y, además, busca ampliar los estudios de la historia arte gráfico en el Perú.
Para este propósito, el artículo parte de una breve reflexión sobre el concepto de ilustración y su capacidad de comunicación. Seguidamente, se pasará al análisis artístico de dos ilustraciones seleccionadas de todo el libro álbum, debido a que reúnen características plásticas que expresan con claridad las propuestas conceptuales del autor. De esta manera, se busca demostrar la artisticidad de la ilustración gráfica y cómo puede ser abordada desde la perspectiva de la historia del arte.
„Die Schweizerhütte”, Moniuszkowska prapremiera spóźniona o blisko dwa stulecia: pytania, hipotezy, nowe perspektywy badawcze
Authors: Zieziula Grzegorz 
Published: August 2021

Dwuaktowa komische Oper zatytułowana Die Schweizerhütte to nieznane, młodzieńcze dzieło Stanisława Moniuszki, które swojego pierwszego wystawienia doczekało się dopiero w 2018 r., a więc po ok. 180 latach od czasu swojego powstania. Niemiecki tekst tego utworu – zasadniczo zapożyczony przez Moniuszkę z opery Carla Bluma Mary, Max und Michel – pomija niektóre fragmenty „pierwowzoru”, zawiera także interpolację nieustalonego autorstwa oraz odmiennie zredagowane didaskalia. W omówieniu problematyki Die Schweizerhütte autor skupia się na analizie uwertury oraz zastosowanych przez kompozytora form arii, duetów, chórów i finałów. Spójność zastosowanych środków kompozytorskich z koncepcją dramaturgiczną dzieła potwierdza m.in. świadome powiązanie tematyczne uwertury z wieloczęściowymi finałami obydwu aktów oraz wprowadzenie motywów przypominających.
Niemieckojęzyczny utwór przyszłego „ojca opery polskiej” dowodzi zatem poważnych przemyśleń wykształconego w Berlinie, dwudziestoletniego zaledwie, operowego nowicjusza na temat sposobów wewnętrznej integracji dzieła i zaskakująco dojrzałej świadomości reguł dramaturgii muzycznej. Wszystko wskazuje na to, że po powrocie do Wilna Moniuszko nie znalazł niestety sprzyjających warunków do dalszego rozwoju swojego talentu. Jednakże o ile za kontynuację i rozwinięcie ambitnych pomysłów dostrzegalnych w Die Schweizerhütte trudno uznać tzw. operetki (pisane przez Moniuszkę na początku lat 40. z myślą o śpiewających aktorach i szerokich kręgach odbiorców), to pomysły te odezwały się zapewne echem w zaginionej dzisiaj, pierwszej „operze seria” polskiego kompozytora zatytułowanej Twardowski i z pewnością ujawniły się w pełni w wileńskiej Halce.
Staje się coraz bardziej oczywiste, że styl operowy Moniuszki od samego początku ściśle powiązany był nie tylko z tradycją lokalną, wzorcami wykształconymi przez Stefaniego, Elsnera i Kurpińskiego, lecz także z poetyką opery europejskiej, przede wszystkim włoskiej i francuskiej. Transfer ten został jednak zapośredniczony przez niemiecką kulturę muzyczną, teatralną i literacką. Pobyt Moniuszki w Berlinie i stworzenie tam pierwszego, niemieckojęzycznego dzieła operowego odegrał zatem kluczową rolę w złożonym procesie absorpcji i syntezy różnych wzorów dramaturgii operowej. Dzięki niemu kompozytor osiągnąć miał z czasem swoją artystyczną dojrzałość.