bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized, controlled clinical trial of autologous stromal vascular fraction cells transplantation to promote mechanical stretch-induced skin regeneration
Authors: Tan Poh-Ching , Chao Pei-Chuan , Cheng Chen , Chen Chu-Hsin , Huang Ru-Lin , Zhou Shuang-Bai , Xie Yun , Li Qing-Feng 
Published: April 2021

Abstract
Background
The regeneration response of the skin to mechanical stretching in vivo has been explored in reconstructive surgery to repair large-scale deformities. The ability of the skin to regenerate limits the reconstructive outcome. Here, we propose an approach in which autologous stromal vascular fraction (SVF) cells and mechanical stretching are combined to overcome this limitation and promote skin regeneration.

Methods
This randomized, blinded, placebo-controlled clinical trial screened 22 participants undergoing tissue expansion with exhausted regeneration. Twenty eligible participants received intradermal injections of the SVF or placebo treatments. Follow-ups were conducted at 4, 8, and 12 weeks to assess efficacy and at 2 years to assess safety. The primary endpoint was the expanded skin thickness at 12 weeks. The secondary endpoints included skin thickness at 4 and 8 weeks, the expansion index (EI), and the skin texture score at 12 weeks.

Results
The skin thickness of the SVF group was significantly higher than that of the control group at both 8 weeks (mean difference 0.78 [95% CI − 1.43 to − 0.11]; p = 0.018) and 12 weeks (0.65 [95% CI − 1.30 to − 0.01]; p = 0.046). In the SVF group, the increase in skin thickness was significant at 4 weeks (0.49 [95% CI − 0.80 to − 0.06]; p = 0.010) to 8 weeks (0.45 [95% CI − 0.92 to 0.02]; p = 0.026) and maintained after 12 weeks, whereas that in the control group was reduced after 8 weeks (0.42 [95% CI − 0.07 to 0.91]; p = 0.037). The SVF group showed greater EI increases than the control group (0.50 [95% CI − 0.00 to 0.99]; p = 0.047). The skin texture scores in the SVF group were greater than those in the control group at 12 weeks. Histologically, SVF-treated expanded skin showed more proliferating cells and blood vessels, and the extracellular matrix volume increased. No severe adverse events occurred.

Conclusions
Transplantation of SVF cells can expedite the potency of mechanical stretch-induced skin regeneration and provide clinical reconstruction with plentiful tissue.

Trial registration
This trial was registered with the Chinese Clinical Trial Registry, ChiCTR2000039317 (registered 23 October 2020—retrospectively registered).
Classical scrapie in small ruminants is caused by at least four different prion strains
Authors: Marín-Moreno Alba , Aguilar-Calvo Patricia , Espinosa Juan Carlos , Zamora-Ceballos María , Pitarch José Luis , González Lorenzo , Fernández-Borges Natalia , Orge Leonor , Andréoletti Olivier , Nonno Romolo , Torres Juan María 
Published: April 2021

AbstractThe diversity of goat scrapie strains in Europe has recently been studied using bioassays in a wide collection of rodent models, resulting in the classification of classical scrapie into four different categories. However, the sole use of the first passage does not lead to isolate adaptation and identification of the strains involved and might therefore lead to misclassification of some scrapie isolates. Therefore, this work reports the complete transmission study of a wide collection of goat transmissible spongiform encephalopathy (TSE) isolates by intracranial inoculation in two transgenic mouse lines overexpressing either small ruminant (TgGoat-ARQ) or bovine (TgBov) PrPC. To compare scrapie strains in sheep and goats, sheep scrapie isolates from different European countries were also included in the study. Once the species barrier phenomenon was overcome, an accurate classification of the isolates was attained. Thus, the use of just two rodent models allowed us to fully differentiate at least four different classical scrapie strains in small ruminants and to identify isolates containing mixtures of strains. This work reinforces the idea that classical scrapie in small ruminants is a prion disease caused by multiple different prion strains and not by a single strain, as is the case for epidemic classical bovine spongiform encephalopathy (BSE-C). In addition, the clear dissimilarity between the different scrapie strains and BSE-C does not support the idea that classical scrapie is the origin of epidemic BSE-C.
RRM2 silencing suppresses malignant phenotype and enhances radiosensitivity via activating cGAS/STING signaling pathway in lung adenocarcinoma
Authors: Jiang Xueping , Li Yangyi , Zhang Nannan , Gao Yanping , Han Linzhi , Li Shuying , Li Jiali , Liu Xingyu , Gong Yan , Xie Conghua 
Published: April 2021

Abstract
Background
As one of the most common malignancy, lung adenocarcinoma (LUAD) is characterized by low 5-year survival rate. This research aimed to investigate the effects of ribonucleotide reductase regulatory subunit M2 (RRM2) on malignant biological behaviors and activation of cGAS/STING pathway. We also explored the synergistic sensitization mechanisms of RRM2 and radiotherapy.

Methods
Bioinformatic tools were used to evaluate the clinical significance of RRM2 in LUAD patients. The roles of RRM2 in malignant phenotype and DNA damage in LUAD cells were investigated with cell proliferation, colony formation, immunofluorescence, modified Boyden chamber and comet assays. The mouse models were used to evaluate the biological significance of RRM2 in vivo. Cytotoxic T cell infiltration was evaluated via flow cytometric analysis and immunohistochemistry staining in C57BL/6 mice. We also explored the synergistic effects of RRM2 silencing and radiation on LUAD cells with apoptosis assay and immunoblotting in vitro.

Results
Bioinformatic analysis revealed that RRM2 had diagnostic values for LUAD patients. Higher levels of RRM2 predicted worse prognosis. RRM2 silencing inhibited LUAD cell proliferation, invasion and migration. RRM2 knockdown induced S phase arrest and DNA damage. RRM2 silencing induced cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway, and the downstream targets were regulated in a STING-dependent manner. Knockdown of RRM2 suppressed tumor growth in the xenograft tumor models. RRM2 deficiency increased CD8 + T cells in the tumor tissues and spleens. Furthermore, RRM2 silencing had synergistic effects with radiation on inhibiting cell proliferation and promoting apoptosis. Meanwhile, this combination promoted the activation of cGAS/STING signaling pathway synergistically, and simultaneously increased expression of IFNβ, CCL5 and CXCL10.

Conclusion
Our results demonstrated that RRM2 silencing had anti-tumor values and activated the cGAS/STING signaling pathway. RRM2 silencing increased CD8 + T cells infiltration. RRM2 silencing cooperated with radiation to inhibit LUAD cell proliferation, promote apoptosis and enhance the activation of cGAS/STING signaling pathway. RRM2 could be a promising target for tumor regression through cancer immunotherapy in LUAD.
Outcome of acute kidney injury: how to make a difference?
Authors: Jamme Matthieu , Legrand Matthieu , Geri Guillaume 
Published: April 2021

Abstract
Background
Acute kidney injury (AKI) is one of the most frequent organ failure encountered among intensive care unit patients. In addition to the well-known immediate complications (hydroelectrolytic disorders, hypervolemia, drug overdose), the occurrence of long-term complications and/or chronic comorbidities related to AKI has long been underestimated. The aim of this manuscript is to briefly review the short- and long-term consequences of AKI and discuss strategies likely to improve outcome of AKI.

Main body
We reviewed the literature, focusing on the consequences of AKI in all its aspects and the management of AKI. We addressed the importance of clinical management for improving outcomes AKI. Finally, we have also proposed candidate future strategies and management perspectives.

Conclusion
AKI must be considered as a systemic disease. Due to its short- and long-term impact, measures to prevent AKI and limit the consequences of AKI are expected to improve global outcomes of patients suffering from critical illnesses.
Arsenic trioxide synergistically promotes the antileukaemic activity of venetoclax by downregulating Mcl-1 in acute myeloid leukaemia cells
Authors: Cho Hyunsoo , Jang Ji Eun , Eom Ju-In , Jeung Hoi-Kyung , Chung Haerim , Kim Jin Seok , Cheong June-Won , Min Yoo Hong 
Published: April 2021

AbstractBackgroundThe evasion of apoptosis through dysregulated Bcl-2 family members is a hallmark of leukaemia stem cells (LSCs) in acute myeloid leukaemia (AML). Therefore, targeting Bcl-2 with venetoclax has been suggested as an attractive strategy for inducing apoptosis in AML LSCs. However, the selective inhibition of Bcl-2 in AML often leads to upregulation of Mcl-1, another dominant anti-apoptotic Bcl-2 family protein conferring venetoclax resistance.MethodsWe assessed the combined effect of venetoclax and arsenic trioxide (ATO) on leukaemic cell viability, apoptosis, combination index, and cell cycle in the human LSC-like KG1 and KG1a cells. The synergistic effect of venetoclax and ATO on apoptosis was also examined in primary CD34+and CD34+CD38−LSCs from the bone marrow (BM) of AML patients, and compared with those from healthy donors.ResultsVenetoclax efficiently impaired cell viability and dose-dependently promoted apoptosis when combined with ATO; their synergism was aptly represented by the combination index. The combination of venetoclax and ATO impaired cell cycle progression by restricting cells within the sub-G1 phase and facilitating caspase-dependent apoptotic cell death associated with the loss of mitochondrial membrane potential, while sparing healthy BM haematopoietic stem cells. Mechanistically, ATO mitigated venetoclax-induced upregulation of Mcl-1 by the inhibition of AKT and ERK, along with activation of GSK-3β. This led to the Mcl-1 destabilisation, triggering Noxa and Bim to facilitate apoptosis and the consequent activation of the apoptosis executioner protein Bak. Moreover, the combination promoted phosphorylation of ATM, Chk2, p38, and H2AX, indicating an active DNA damage response.ConclusionsOur findings demonstrate the synergistic, preferential antileukaemic effects of venetoclax and ATO on LSCs, providing a rationale for preclinical and clinical trials by combining these agents already being used in clinical practice to treat acute leukaemia.
Epidemiology of dengue virus infections in Nepal, 2006–2019
Authors: Rijal Komal Raj , Adhikari Bipin , Ghimire Bindu , Dhungel Binod , Pyakurel Uttam Raj , Shah Prakash , Bastola Anup , Lekhak Binod , Banjara Megha Raj , Pandey Basu Dev , Parker Daniel M. , Ghimire Prakash 
Published: April 2021

AbstractBackgroundDengue is one of the newest emerging diseases in Nepal with increasing burden and geographic spread over the years. The main objective of this study was to explore the epidemiological patterns of dengue since its first outbreak (2006) to 2019 in Nepal.MethodsThis study is a retrospective analysis that covers the last 14 years (2006–2019) of reported dengue cases from Epidemiology Diseases Control Division (EDCD), Ministry of Health and Population, Government of Nepal.Reported cases were plotted over time and maps of reported case incidence were generated (from 2016 through 2019). An ecological analysis of environmental predictors of case incidence was conducted using negative binomial regression.ResultsWhile endemic dengue has been reported in Nepal since 2006, the case load has increased over time and in 2019 a total of 17 992 dengue cases were reported from 68 districts (from all seven provinces). Compared to the case incidence in 2016, incidence was approximately five times higher in 2018 [incidence rate ratio (IRR): 4.8; 95% confidence interval (CI) 1.5–15.3] and over 140 times higher in 2019 (IRR: 141.6; 95%CI45.8–438.4). A one standard deviation increase in elevation was associated with a 90% decrease in reported case incidence (IRR: 0.10; 95%CI0.01–0.20). However, the association between elevation and reported cases varied across the years. In 2018 there was a cluster of cases reported from high elevation Kaski District of Gandaki Province. Our results suggest that dengue infections are increasing in magnitude and expanding out of the lowland areas to higher elevations over time.ConclusionsThere is a high risk of dengue outbreak in the lowland Terai region, with increasing spread towards the mid-mountains and beyond as seen over the last 14 years. Urgent measures are required to increase the availability of diagnostics and resources to mitigate future dengue epidemics.
Brain insulin signaling and cerebrovascular disease in human postmortem brain
Authors: Arvanitakis Zoe , Capuano Ana W. , Wang Hoau-Yan , Schneider Julie A. , Kapasi Alifiya , Bennett David A. , Ahima Rexford S. , Arnold Steven E. 
Published: April 2021

AbstractInsulin is an important hormone for brain function, and alterations in insulin metabolism may be associated with neuropathology. We examined associations of molecular markers of brain insulin signaling with cerebrovascular disease. Participants were enrolled in the Religious Orders Study (ROS), an ongoing epidemiologic community-based, clinical-pathologic study of aging from across the United States. Using cross-sectional analyses, we studied a subset of ROS: 150 persons with or without diabetes, matched 1:1 by sex on age-at-death and education. We used ELISA, immunohistochemistry, and ex vivo stimulation with insulin, to document insulin signaling in postmortem midfrontal gyrus cortex tissue. Postmortem neuropathologic data identified cerebrovascular disease including brain infarcts, classified by number (as none for the reference; one; and more than one), size (gross and microscopic infarcts), and brain region/location (cortical and subcortical). Cerebral vessel pathologies were assessed, including severity of atherosclerosis, arteriolosclerosis, and amyloid angiopathy. In separate regression analyses, greater AKT1 phosphorylation at T308 following ex vivo stimulation with insulin (OR = 1.916; estimate = 0.650; p = 0.007) and greater pS616IRS1 immunolabeling in neuronal cytoplasm (OR = 1.610; estimate = 0.476; p = 0.013), were each associated with a higher number of brain infarcts. Secondary analyses showed consistent results for gross infarcts and microinfarcts separately, but no other association including by infarct location (cortical or subcortical). AKT S473 phosphorylation following insulin stimulation was associated with less amyloid angiopathy severity, but not with other vessel pathology including atherosclerosis and arteriolosclerosis. In summary, insulin resistance in the human brain, even among persons without diabetes, is associated with cerebrovascular disease and especially infarcts. The underlying pathophysiologic mechanisms need further elucidation. Because brain infarcts are known to be associated with lower cognitive function and dementia, these data are relevant to better understanding the link between brain metabolism and brain function.
A reconstruction error-based framework for label noise detection
Authors: Salekshahrezaee Zahra , Leevy Joffrey L. , Khoshgoftaar Taghi M. 
Published: April 2021

AbstractLabel noise is an important data quality issue that negatively impacts machine learning algorithms. For example, label noise has been shown to increase the number of instances required to train effective predictive models. It has also been shown to increase model complexity and decrease model interpretability. In addition, label noise can cause the classification results of a learner to be poor. In this paper, we detect label noise with three unsupervised learners, namely$$\textit{principal component analysis} \hbox { (PCA)}$$principal componentanalysis(PCA),$$\textit{independent component analysis} \hbox { (ICA)}$$independent componentanalysis(ICA), and autoencoders. We evaluate these three learners on a credit card fraud dataset using multiple noise levels, and then compare results to the traditional Tomek links noise filter. Our binary classification approach, which considers label noise instances as anomalies, uniquely uses reconstruction errors for noisy data in order to identify and filter label noise. For detecting noisy instances, we discovered that the autoencoder algorithm was the top performer (highest recall score of 0.90), while Tomek links performed the worst (highest recall score of 0.62).
Web-based authentic inquiry experiences in large introductory classes consistently associated with significant learning gains for all students
Authors: Wu X. Ben , Sandoval Carolyn , Knight Stephanie , Jaime Xavier , Macik Maria , Schielack Jane F. 
Published: April 2021

AbstractBackgroundContinuous calls for reform in science education emphasize the need to provide science experiences in lower-division courses to improve the retention of STEM majors and to develop science literacy and STEM skills for all students. Open or authentic inquiry and undergraduate research are effective science experiences leading to multiple gains in student learning and development. Most inquiry-based learning activities, however, are implemented in laboratory classes and the majority of them are guided inquiries. Although course-based undergraduate research experiences have significantly expanded the reach of the traditional apprentice approach, it is still challenging to provide research experiences to nonmajors and in large introductory courses. We examined student learning through a web-based authentic inquiry project implemented in a high-enrollment introductory ecology course for over a decade.ResultsResults from 10 years of student self-assessment of learning showed that the authentic inquiry experiences were consistently associated with significant gains in self-perception of interest and understanding and skills of the scientific process for all students—both majors and nonmajors, both lower- and upper-division students, both women and men, and both URM and non-URM students. Student performance in evaluating the quality of an inquiry report, before and after the inquiry project, also showed significant learning gains for all students. The authentic inquiry experiences proved highly effective for lower-division students, nonmajors, and women and URM students, whose learning gains were similar to or greater than those of their counterparts. The authentic inquiry experiences were particularly helpful to students who were less prepared with regard to the ability to evaluate a scientific report and narrowed the performance gap.ConclusionsThese findings suggest that authentic inquiry experiences can serve as an effective approach for engaging students in high-enrollment, introductory science courses. They can facilitate development of science literacy and STEM skills of all students, skills that are critical to students’ personal and professional success and to informed engagement in civic life.
Weak faults at megathrust plate boundary respond to tidal stress
Authors: Tonegawa Takashi , Kimura Toshinori , Shiraishi Kazuya , Yabe Suguru , Fukao Yoshio , Araki Eiichiro , Kinoshita Masataka , Sanada Yoshinori , Miura Seiichi , Nakamura Yasuyuki , Kodaira Shuichi 
Published: April 2021

AbstractLateral spatial variations of weak portions at the plate boundary in subduction zones have been estimated primarily by the distribution of slow earthquakes mainly occurring around seismogenic zones. However, the detailed depth profile of weak faults remains elusive. Here, we deployed six ocean bottom seismometers in the Nankai subduction zone, Japan, to observe reflections originated from drilling vesselChikyuship noise (hydroacousticPwave) that was persistently radiated from a fixed position at the sea surface, and retrievedP-to-s(Ps) reflections from multiple dipping faults near the plate boundary. ThePsamplitudes were stacked and compared according to the degrees of tidal stresses, and high amplitudes were observed at high tide (compression). A migration technique shows that the locations where velocity contrasts fluctuate were estimated at both the megasplay fault and another fault between the megasplay fault and the top of the oceanic crust. This indicates that the physical properties of these faults are altered by tidal stress. The physical-property changes are attributed to fluid connections and isolations within the faults due to tidal stress fluctuations, inducing the variation of seismic anisotropy. Such a variation was confirmed by a three-dimensional numerical simulation for wave propagation with anisotropic medium. Our observation suggests that multiple weak faults are present around the plate boundary, and the obtained changes of fault physical properties may have implications for in-depth understanding of tidal triggering of earthquakes.
A serious-gamification blueprint towards a normalized attention
Authors: Alqithami Saad 
Published: April 2021

AbstractAttention is an important commodity in the human skills set. It can be trained to overcome deficits in the short term which might be based on multiple cognitive complications to entail inability to keep focus and mined wondering. On the long term, however, it might be a symptom of chronic diseases that acquire attention to include the spectra of many mental health disorders, e.g., attention deficit hyperactivity disorder (ADHD). This paper, therefore, introduces a generic reference model that guides in the design of proper treatment method for patients in short of attention to engage in a game-based environment in order to enhance the behavior of their current state of attention which may hopefully lead to a better focus. When considering the volatility of traditional cognitive behavioral therapies (CBTs), the model reflects and analyzes evolving serious games design directed for the treatment of ADHD. It serves as an instrument that spawn over a specific treatment design since it introduces essential components that depicts essential units of traditional CBT when they are modularly combined. The components will be introduced and the processes of the reference model will be elaborated as a roadmap for the formation and the operation of augmented reality treatment games.
Successful treatment of adult cecorectal intussusception caused by cecum cancer with mobile cecum: a case report
Authors: Shimoyama Hayato , Ueno Kimihiko , Samizo Masahiro 
Published: April 2021

AbstractBackgroundIntussusception occurs when a segment of the bowel (the intussusceptum) telescopes into an adjacent segment (the intussuscipiens). Adult intussusception occurs rarely and often requires surgical resection for its treatment. We describe the case of an adult patient with extremely rare cecorectal intussusception treated using a novel combined transabdominal and trans-anal approach, which has not yet been reported in the literature.Case presentationA 71-year-old woman was transferred to our hospital for the treatment of upper abdominal pain. Physical examination, laboratory tests, and imaging inspections showed strangulated bowel obstruction induced by intussusception associated with the intra-rectal mass. We performed an emergency operation and treated the intussusception using a combined transabdominal and trans-anal approach. The intraoperative findings revealed bloody ascites and a potentially malignant tumor that had moved toward the anal side from peritoneal reflection. The tumor served as the lead point in the cecum with mobile cecum. After reducing the intussusception using the combined procedure, we removed the ileocecal portion. The intraoperative and histopathological findings suggested that cecum cancer with mobile cecum had caused the cecorectal intussusception. The patient had an uneventful postoperative course, except for postoperative pulmonary pneumonia.ConclusionTo the best of our knowledge, this is the first reported case of adult cecorectal intussusception due to cecum cancer with mobile cecum successfully treated using the combined transabdominal and trans-anal approach. This combined procedure may be useful in treating the intussusception where the lead point is distal from the peritoneal reflection.