bluuebunny/crossref_metadata_2025_split huggingface dataset:
The global Cenozoic diversification process of tortoises (Testudinidae)
Authors: Oliveira Isabela , Liparini Alexandre , Martinez Pablo A. , Eduardo Anderson A. 
Published: March 2023

AbstractGreat environmental changes may affect the survival capability of a variety of organisms. Testudinidae is the most diverse family of terrestrial chelonians within the whole order (Testudines). Interestingly, however, the number of extinct species overcome the extant ones. In order to understand better how the diversification process of this family occurred, this work used the PyRate software, which estimates both the preservation and diversification processes in a continuous time interval. For such, the software used a list of fossil occurrences obtained from the Paleobiology Database whereas the extant species list was obtained from Catalogue of Life. This way, the software was able to infer the probability of the ancestral clade having resulted in these species during its evolutionary history. The analyses generated graphs containing the diversification, extinction and speciation curves and their respective associated 95% credibility intervals. A great rise in the extinction rate was observed starting 6 million years ago. This rise is believed to be related to the drop of atmospheric CO2 all over the globe at the end of the Miocene, about 8–6 million years ago. This event led to a turnover of the vegetation composition on the warmer areas of the planet, with plants that used C3 metabolism giving way to C4 plants. In terms of landscape, grasses and herbal vegetation, such as savannas, started dominating. As for other animal groups, those herbivores with grazing habits were more successful than those used to only browsing or that did not have enough flexibility of choice.
A mixed method analysis of student satisfaction with active learning techniques in an online graduate anatomy course: Consideration of demographics and previous course enrollment
Authors: Bradley Libby J. , Meyer Kimberly E. , Robertson Taylor C. , Kerr Marcel Satsky , Maddux Scott D. , Heck Amber J. , Reeves Rustin E. , Handler Emma K. 
Published: March 2023

AbstractOnline learning has become an essential part of mainstream higher education. With increasing enrollments in online anatomy courses, a better understanding of effective teaching techniques for the online learning environment is critical. Active learning has previously shown many benefits in face‐to‐face anatomy courses, including increases in student satisfaction. Currently, no research has measured student satisfaction with active learning techniques implemented in an online graduate anatomy course. This study compares student satisfaction across four different active learning techniques (jigsaw, team‐learning module, concept mapping, and question constructing), with consideration of demographics and previous enrollment in anatomy and/or online courses. Survey questions consisted of Likert‐style, multiple‐choice, ranking, and open‐ended questions that asked students to indicate their level of satisfaction with the active learning techniques. One hundred seventy Medical Science master's students completed the online anatomy course and all seven surveys. Results showed that students were significantly more satisfied with question constructing and jigsaw than with concept mapping and team‐learning module. Additionally, historically excluded groups (underrepresented racial minorities) were generally more satisfied with active learning than non‐minority groups. Age, gender, and previous experience with anatomy did not influence the level of satisfaction. However, students with a higher‐grade point average (GPA), those with only a bachelor's degree, and those with no previous online course experience were more satisfied with active learning than students who had a lower GPA, those holding a graduate/professional degree, and those with previous online course experience. Cumulatively, these findings support the beneficial use of active learning in online anatomy courses.
Investigating the impact of disposable surgical face‐masks on face identity and emotion recognition in adults with autism spectrum disorder
Authors: Ventura Martina , Innamorato Fiorita , Palmisano Annalisa , Cicinelli Giovanni , Nobile Emanuela , Manippa Valerio , Keller Roberto , Rivolta Davide 
Published: March 2023

AbstractWith the outburst of the COVID‐19 pandemic, disposable surgical face‐masks (DSFMs) have been widely adopted as a preventive measure. DSFMs hide the bottom half of the face, thus making identity and emotion recognition very challenging, both in typical and atypical populations. Individuals with autism spectrum disorder (ASD) are often characterized by face processing deficits; thus, DSFMs could pose even a greater challenge for this population compared to typically development (TD) individuals. In this study, 48 ASDs of level 1 and 110 TDs underwent two tasks: (i) the Old‐new face memory task, which assesses whether DSFMs affect face learning and recognition, and (ii) the Facial affect task, which explores DSFMs' effect on emotion recognition. Results from the former show that, when faces were learned without DSFMs, identity recognition of masked faces decreased for both ASDs and TDs. In contrast, when faces were first learned with DSFMs, TDs but not ASDs benefited from a “context congruence” effect, that is, faces wearing DSFMs were better recognized if learned wearing DSFMs. In addition, results from the Facial affect task show that DSFMs negatively impacted specific emotion recognition in both TDs and ASDs, although differentially between the two groups. DSFMs negatively affected disgust, happiness and sadness recognition in TDs; in contrast, ASDs performance decreased for every emotion except anger. Overall, our study demonstrates a general, although different, disruptive effect on identity and emotion recognition both in ASD and TD population.
Yolk sac development, function and role in rodent pregnancy
Authors: Ornoy Asher , Miller Richard K. 
Published: March 2023

AbstractDuring the early phases of embryonic development, the yolk sac serves as an initial placenta in many animal species. While in some, this role subsides around the end of active organogenesis, it continues to have important functions in rodents, alongside the chorio‐allantoic placenta. The yolk sac is the initial site of hematopoiesis in many animal species including primates. Cells of epiblastic origin form blood islands that are the forerunners of hematopoietic cells and of the primitive endothelial cells that form the vitelline circulation. The yolk sac is also a major route of embryonic and fetal nutrition apparently as long as it functions. In mammals and especially rodents, macro and micronutrients are absorbed by active pinocytosis into the visceral yolk sac, degraded and the degradation products (i.e., amino acids) are then transferred to the embryo. Interference with the yolk sac function may directly reflect on embryonic growth and development, inducing congenital malformations or in extreme damage, causing embryonic and fetal death. In rodents, many agents were found to damage the yolk sac (i.e., anti–yolk sac antibodies or toxic substances interfering with yolk sac pinocytosis) subsequently affecting the embryo/fetus. Often, the damage to the yolk sac is transient while embryonic damage persists. In humans, decreased yolk sac diameter was associated with diabetic pregnancies and increased diameter was associated with pregnancy loss. In addition, culture of rat yolk sacs in serum obtained from pregnant diabetic women or from women with autoimmune diseases induced severe damage to the visceral yolk sac epithelium and embryonic malformations. It can be concluded that as a result of the crucial role of the yolk sac in the well‐being of the early embryo, any damage to its normal function may severely and irreversibly affect further development of the embryo/fetus.
Fully integrated downstream process to enable next‐generation manufacturing
Authors: Ramos Irina , Sharda Nikunj , Villafana Ramon , Hill‐Byrne Kevin , Cai Kang , Pezzini Joanna , Coffman Jon 
Published: March 2023

AbstractNext‐generation manufacturing (NGM) has evolved over the past decade to a point where large biopharmaceutical organizations are making large investments in the technology and considering implementation in clinical and commercial processes. There are many well‐considered reasons to implement NGM. For the most part, organizations will not fund NGM unless the implementation benefits the funding organization by providing reduced costs, reduced time, or additional needed capabilities. Productivity improvements gained from continuous purification are shown in this work, which used a new system that fully integrates and automates several downstream unit operations of a biopharmaceutical process to provide flexibility and easy implementation of NGM. The equipment and automation needed to support NGM can be complicated and expensive. Biopharmaceutical Process Development considered two options as follows: (1) design its own NGM system or (2) buy a prebuilt system. PAK BioSolutions offers a turn‐key automated and integrated system that can operate up to four continuous purification stages simultaneously, while maintaining a small footprint in the manufacturing plant. The system provides significant cost benefits (~10× lower) compared with the alternative—integration of many different pieces of equipment through a Distributed Control System that would require significant engineering time for design, automation, and integration. Integrated and Continuous Biomanufacturing can lead to significant reductions in facility size, reduced manufacturing costs, and enhanced product quality when compared with the traditional batch mode of operation. The system uses new automation strategies that robustly link unit operations. We present the optimized process fit, sterility and bioburden control strategy, and automation features (such as pH feedback control and in‐line detergent addition), which enabled continuous operation of a 14‐day end‐to‐end monoclonal antibody purification process at the clinical manufacturing scale.
Identification of the anti‐inflammatory quality markers of Chrysanthemi Flos (Juhua) using spectrum–effect relationships combined with bioactivity re‐evaluation
Authors: Liu Dan , Zhu Qianqian , Zhang Lian , Wang Shiqin , Yin Xuan , Wu Shiyu , Wang Bo , Ye Xiaochuan , Nie Jing 
Published: March 2023

AbstractChrysanthemi Flos (Juhua), an edible herbal medicine that possesses efficacies of dispersing wind, clearing heat and detoxifying. Studies have demonstrated that the health benefits of Chrysanthemi Flos are largely attributable to its anti‐inflammatory effects. However, the correlation between the compounds monitored by the current quality control methods and the anti‐inflammatory effects of Chrysanthemi Flos is unclear. In order to better control the quality of Chrysanthemi Flos, the identification of anti‐inflammatory quality markers (Q‐markers) of Chrysanthemi Flos was performed. The chemical components of Chrysanthemi Flos were profiled by HPLC fingerprints combined with chemometrics methods. Simultaneously, the anti‐inflammatory activities of 10 batches of water extracts of Chrysanthemi Flos were evaluated in lipopolysaccharide‐activated RAW 264.7 macrophages cells. Gray correlation analysis was performed to assess the relationship between the anti‐inflammatory activity and chemical properties. The results showed that 13 common peaks were closely correlated with the anti‐inflammatory effect, and further bioactivity re‐evaluation confirmed that 10 known compounds exerted a strong anti‐inflammatory effect. The quantitative analysis of the 10 Q‐markers showed that the 25 batches of samples could be discriminated into different zones according to their producing areas. Conclusively, the present work identified 10 anti‐inflammatory Q‐markers of Chrysanthemi Flos using spectrum–effect relationships combined with bioactivity re‐evaluation.
Survival and prognostic factors of early‐stage non‐small cell lung cancer in Central and Eastern Europe: A prospective cohort study
Authors: Sheikh Mahdi , Virani Shama , Robbins Hilary A. , Foretova Lenka , Holcatova Ivana , Janout Vladimir , Lissowska Jolanta , Navratilova Marie , Mukeriya Anush , Ognjanovic Miodrag , Swiatkowska Beata , Zaridze David , Brennan Paul 
Published: March 2023

AbstractBackgroundAlthough early diagnosis and surgical resection of the tumor have been shown to be the most important predictors of lung cancer survival, long‐term survival for surgically‐resected early‐stage lung cancer remains poor.AimsIn this prospective study we aimed to investigate the survival and prognostic factors of surgically‐resected early‐stage non‐small cell lung cancer (NSCLC) in Central and Eastern Europe.MethodsWe recruited 2052 patients with stage I‐IIIA NSCLC from 9 centers in Russia, Poland, Serbia, Czech Republic, and Romania, between 2007–2016 and followed them annually through 2020.ResultsDuring follow‐up, there were 1121 deaths (including 730 cancer‐specific deaths). Median survival time was 4.9 years, and the 5‐year overall survival was 49.5%. In the multivariable model, mortality was increased among older individuals (HR for each 10‐year increase: 1.31 [95% CI: 1.21–1.42]), males (HR:1.24 [1.04–1.49]), participants with significant weight loss (HR:1.25 [1.03–1.52]), current smokers (HR:1.30 [1.04–1.62]), alcohol drinkers (HR:1.22 [1.03–1.44]), and those with higher stage tumors (HR stage IIIA vs. I: 5.54 [4.10 – 7.48]). However, education, chronic obstructive pulmonary diseases (COPD), and tumor histology were not associated with risk of death. All baseline indicators of smoking and alcohol drinking showed a dose‐dependent association with the risk of cancer‐specific mortality. This included pack‐years of cigarettes smoked (p‐trend = 0.04), quantity of smoking (p‐trend = 0.008), years of smoking (p‐trend = 0.010), gram‐days of alcohol drank (p‐trend = 0.002), frequency of drinking (p‐trend = 0.006), and years of drinking (p‐trend = 0.016).ConclusionThis study shows that the 5‐year survival rate of surgically‐resected stage I‐IIIA NSCLC is still around 50% in Central and Eastern Europe. In addition to non‐modifiable prognostic factors, lifetime patterns of smoking and alcohol drinking affected the risk of death and disease progression in a dose‐dependent manner in this population.
Performance of a PLK1‐based immune risk model for prognosis and treatment response prediction in breast cancer
Authors: Chen Yan , You Yiqing , Wu Qiaoling , Wu Jing , Lin Shujing , Sun Yang , Cui Zhaolei 
Published: March 2023

AbstractObjectivePolo‐like kinase 1 (PLK1), a serine/threonine‐protein kinase, functions as a potent oncogene in the initiation and progression of tumor. The aim of this study is to assess potential correlations between PLK1 expression and immune infiltration in breast cancer (BRCA) and construct a PLK1‐based immune risk model applicable for prognosis and treatment response prediction in BRCA.MethodsWe collected data on PLK1 gene expression in BRCA patients from The Cancer Genome Atlas (TCGA) database. Thereafter, we analyzed the associations of PLK1 expression with immune cell infiltration and immunomodulators, and established a prognostic risk model based on seven PLK1‐associated immunomodulator genes and a nomogram for survival prediction.ResultsBRCA prognosis, clinical stage progression, and tumor classification were all shown to be substantially correlated with PLK1 expression. The PLK1 gene was significantly enriched in T cell and B cell receptors and molecules of the chemokine signaling pathways. Specifically, PLK1 expression was positively correlated with the CD8+ T cell and regulatory T cell (Tregs) activation and negatively correlated with M2 macrophage infiltration. The seven‐genes‐based risk model could serve as an independent prognostic factor of BRCA. The risk model was markedly correlated with the expression of programmed cell death protein 1/programmed cell death ligand 1 (PD‐1/PD‐L1; both p < 0.001) immune checkpoints, and tumor mutation burden (TMB). High‐ and low‐risk BRCA patients identified by the risk model responded differently to anti‐PD‐1 and/or anti‐CTLA4 therapy, as well as common chemotherapy drugs, like cisplatin, paclitaxel, and gemcitabine.ConclusionThis PLK1‐based immune risk model can effectively predict the prognosis and tumor progression of BRCA, identify gene mutations, and evaluate patient's response toward immunotherapy and chemotherapy regimens.
Androgen promotes squamous differentiation of atypical cells in cervical intraepithelial neoplasia via an ELF3‐dependent pathway
Authors: Matsumoto Takeo , Suzuki Takuma , Nakamura Mitsuhiro , Yamamoto Megumi , Iizuka Takashi , Ono Masanori , Kagami Kyosuke , Kasama Haruki , Kanda Tatsuhito , Sakai Yuya , Iwadare Junpei , Matsuoka Ayumi , Kayahashi Kayo , Wakae Kousho , Muramatsu Masamichi , Kyo Satoru , Yamamoto Yasuhiko , Mizumoto Yasunari , Daikoku Takiko , Fujiwara Hiroshi 
Published: March 2023

AbstractBackgroundSince the human papillomavirus vaccines do not eliminate preexisting infections, nonsurgical alternative approaches to cervical intraepithelial neoplasia (CIN) have been required. We previously reported that FOXP4 (forkhead box transcription factor P4) promoted proliferation and inhibited squamous differentiation of CIN1‐derived W12 cells. Since it was reported that FOXP expressions were regulated by the androgen/androgen receptor (AR) complex and AR was expressed on the CIN lesions, in this study we examined the effects of androgen on CIN progression.MethodsSince AR expression was negative in W12 cells and HaCaT cells, a human male skin‐derived keratinocyte cell line, we transfected AR to these cell lines and investigated the effects of dihydrotestosterone (DHT) on their proliferation and squamous differentiation. We also examined the immunohistochemical expression of AR in CIN lesions.ResultsDHT reduced the intranuclear expression of FOXP4, attenuating cell proliferation and promoting squamous differentiation in AR‐transfected W12 cells. Si‐RNA treatments showed that DHT induced the expression of squamous differentiation‐related genes in AR‐transfected W12 cells via an ELF3‐dependent pathway. DHT also reduced FOXP4 expression in AR‐transfected HaCaT cells. An immunohistochemical study showed that AR was expressed in the basal to parabasal layers of the normal cervical epithelium. In CIN1 and 2 lesions, AR was detected in atypical squamous cells, whereas AR expression had almost disappeared in the CIN3 lesion and was not detected in SCC, suggesting that androgens do not act to promote squamous differentiation in the late stages of CIN.ConclusionAndrogen is a novel factor that regulates squamous differentiation in the early stage of CIN, providing a new strategy for nonsurgical and hormone‐induced differentiation therapy against CIN1 and CIN2.
Anti‐tumor effects of miR‐34a by regulating immune cells in the tumor microenvironment
Authors: Yin Man , Zhang Zhiqiang , Wang Yunfei 
Published: March 2023

AbstractMalignant tumors pose a serious threat to human health. The development of malignant tumors is characterized by uncontrolled cell division and immune evasion. The micro‐ribonucleic acid‐34a (miR‐34a) is a small noncoding single‐stranded ribonucleic acid that is ubiquitously present in normal human tissues. However, it has been confirmed to be dysregulated in a variety of tumor cells. Numerous research have revealed the importance of miR‐34a in the treatment of various malignancies. MiR‐34a deletion can hasten the growth of tumors whereas miR‐34a overexpression suppresses the proliferation, invasion, and migration of cancer cells. Moreover, more recent studies have highlighted its role in immunity and investigated its applicability to particular tumors. Through various immune cells, factors, and other mechanisms, miR‐34a can inhibit tumor carcinogenesis. In view of the important role of miR‐34a in tumors, this research reviewed the aspects of miR‐34a regulation of tumor immune microenvironment to exert anti‐tumor effects in order to clarify the potential immunotherapy value of miR‐34a in tumors.
Impact of residual disease biomarkers on the prognosis of HER2‐positive breast cancer following neoadjuvant therapy
Authors: Ma Youzhao , Zhu Mingda , Lv Minhao , Yuan Peng , Chen Xiuchun , Liu Zhenzhen 
Published: March 2023

AbstractBackgroundThe changes in prognostic factors and clinicopathological characteristics of residual disease following neoadjuvant therapy (NAT) for breast cancer are important references for postoperative adjuvant therapy. The analyses of the relationship between the clinicopathological characteristics of residual diseases and the prognosis were not comprehensive in most previous studies. This study aimed to determine how prognostic factors changed following NAT and the impact of clinicopathological characteristics of residual disease on the prognosis of human epidermal growth factor receptor 2 (HER2)‐positive breast cancer.MethodsThe study comprised 350 consecutive patients with HER2‐positive breast cancer who had residual disease after surgery following NAT. The independent risk factors affecting the prognosis of HER2‐positive breast cancer were analyzed using univariate and multivariate Cox regression analyses. Chi‐square test and binary logistic regression were used to analyze the influencing factors of HER2 loss following NAT.ResultsThe expression of prognostic factors changed significantly following NAT. A total of 44 patients (12.6%) had HER2 loss. HER2 status (immunohistochemistry (IHC) 3+ vs. IHC 2+/FISH+, p < 0.001) at baseline was associated with HER2 loss. In this investigation, the HER2 loss did not affect the prognosis. In univariate analysis, the decrease in Ki‐67 (p < 0.001) after NAT was associated with improved prognosis, but this influence was lost in the Cox proportional hazards model. The ypN stage (p < 0.001), postoperative ER status (p = 0.020), Miller–Payne grade (p = 0.007), and targeted therapy (p = 0.003) were all independent prognostic factors.ConclusionsER, PR, HER2, and Ki‐67 changed significantly after NAT, but no impact of these changes on DFS was observed in this study. Postoperative N stage, postoperative ER status, MP grade, and targeted therapy were independent prognostic factors in patients with HER2‐positive breast cancer after NAT.