bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circ-KIAA0907 inhibits the progression of oral squamous cell carcinoma by regulating the miR-96-5p/UNC13C axis
Authors: Dong Wenjie , Zhao Lei , Zhang Shiyang , Zhang Shijie , Si Hongyun 
Published: March 2021

Abstract
Background
Circular RNA (circRNA) plays an important role in regulating cell biological function and has been shown to be involved in cancer progression, including oral squamous cell carcinoma (OSCC). Circ-KIAA0907 has been found to play an anti-cancer role in OSCC, so it is worth exploring more functions and new mechanisms of circ-KIAA0907 in OSCC progression.

Methods
Quantitative real-time PCR (qRT-PCR) was used to detect the expression of circ-KIAA0907, microRNA (miR)-96-5p, and unc-13 homolog C (UNC13C). Transwell assay, flow cytometry, and colony formation assay were employed to measure the migration, invasion, apoptosis, and radiosensitivity of cells. Besides, glucose uptake, lactate production, and extracellular acidification rate (ECAR) were determined to evaluate the glycolysis ability of cells. Dual-luciferase reporter assay and RIP assay were performed to confirm the interactions among circ-KIAA0907, miR-96-5p, and UNC13C. And RNA pull-down assay was used to verify the binding degree of miR-96-5p to its targets. Moreover, UNC13C protein level was examined using western blot (WB) analysis. OSCC xenograft models were constructed to perform in vivo experiments.

Results
Circ-KIAA0907 was a stability circRNA with lowly expression in OSCC. Overexpressed circ-KIAA0907 could inhibit migration, invasion, and glycolysis, while promoting apoptosis and radiosensitivity in OSCC cells. In the terms of mechanism, circ-KIAA0907 could sponge miR-96-5p to regulate UNC13C expression. MiR-96-5p overexpression could reverse the inhibitory effect of circ-KIAA0907 on OSCC progression, and UNC13C knockdown also could overturn the suppressive effect of miR-96-5p inhibitor on OSCC progression. Animal experiments revealed that circ-KIAA0907 could reduce the tumor growth of OSCC by regulating the miR-96-5p/UNC13C axis.

Conclusion
Our study suggests that circ-KIAA0907 restrains OSCC progression via the miR-96-5p/UNC13C axis, indicating that it may be a potential target for OSCC treatment.
Fatigue in young adults with juvenile idiopathic arthritis 18 years after disease onset: data from the prospective Nordic JIA cohort
Authors:   on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR), Arnstad Ellen Dalen , Glerup Mia , Rypdal Veronika , Peltoniemi Suvi , Fasth Anders , Nielsen Susan , Zak Marek , Aalto Kristiina , Berntson Lillemor , Nordal Ellen , Herlin Troels , Romundstad Pål Richard , Rygg Marite 
Published: March 2021

Abstract
Background
To study fatigue in young adults with juvenile idiopathic arthritis (JIA) 18 years after disease onset, and to compare with controls.

Methods
Consecutive children with onset of JIA between 1997 and 2000, from geographically defined areas of Norway, Sweden, Denmark and Finland were followed for 18 years in a close to population-based prospective cohort study. Clinical features, demographic and patient-reported data were collected. Inclusion criteria in the present study were a baseline visit 6 months after disease onset, followed by an 18-year follow-up with available self-reported fatigue score (Fatigue Severity Scale (FSS), 1–7). Severe fatigue was defined as FSS ≥4. For comparison, Norwegian age and sex matched controls were used.

Results
Among 377 young adults with JIA, 26% reported severe fatigue, compared to 12% among controls. We found higher burden of fatigue among participants with sleep problems, pain, poor health, reduced participation in school/work, physical disability, active disease, or use of disease-modifying anti-rheumatic drugs (DMARDs)/biologics/systemic steroids. In contrast, participants without these challenges, had fatigue scores similar to controls. Active disease assessed at all three time points (baseline, 8-year and 18-year follow-up) was associated with higher mean fatigue score and higher percentage of severe fatigue compared to disease courses characterized by periods of inactive disease. Predictors of fatigue at the 18-year follow-up were female sex and diagnostic delay of ≥6 months at baseline, and also pain, self-reported poor health, active disease, and previous/ongoing use of DMARDs/biologics at 8 years.

Conclusions
Fatigue is a prominent symptom in young adults with JIA, with higher fatigue burden among participants with poor sleep, pain, self-reported health problems, active disease, or use of DMARDs/biologics. Participants without these challenges have results similar to controls. Patient- and physician-reported variables at baseline and during disease course predicted fatigue at 18-year follow-up.
Senescent accelerated prone 8 (SAMP8) mice as a model of age dependent neuroinflammation
Authors: Fernández Andrés , Quintana Elena , Velasco Patricia , Moreno-Jimenez Belén , de Andrés Belén , Gaspar Maria Luisa , Liste Isabel , Vilar Marçal , Mira Helena , Cano Eva 
Published: March 2021

Abstract
Background
Aging and age-related diseases are strong risk factors for the development of neurodegenerative diseases. Neuroinflammation (NIF), as the brain’s immune response, plays an important role in aged associated degeneration of central nervous system (CNS). There is a need for well characterized animal models that will allow the scientific community to understand and modulate this process.

Methods
We have analyzed aging-phenotypical and inflammatory changes of brain myeloid cells (bMyC) in a senescent accelerated prone aged (SAMP8) mouse model, and compared with their senescence resistant control mice (SAMR1). We have performed morphometric methods to evaluate the architecture of cellular prolongations and determined the appearance of Iba1+ clustered cells with aging. To analyze specific constant brain areas, we have performed stereology measurements of Iba1+ cells in the hippocampal formation. We have isolated bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch), and analyzed their response to systemic lipopolysaccharide (LPS)-driven inflammation.

Results
Aged 10 months old SAMP8 mice present many of the hallmarks of aging-dependent neuroinflammation when compared with their SAMR1 control, i.e., increase of protein aggregates, presence of Iba1+ clusters, but not an increase in the number of Iba1+ cells. We have further observed an increase of main inflammatory mediator IL-1β, and an augment of border MHCII+Iba1+ cells. Isolated CD45+ bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch) have been analyzed, showing that there is not a significant increase of CD45+ cells from the periphery. Our data support that aged-driven pro-inflammatory cytokine interleukin 1 beta (IL-1β) transcription is enhanced in CD45+BP cells. Furthermore, LPS-driven systemic inflammation produces inflammatory cytokines mainly in border bMyC, sensed to a lesser extent by the BP bMyC, showing that IL-1β expression is further augmented in aged SAMP8 compared to control SAMR1.

Conclusion
Our data validate the SAMP8 model to study age-associated neuroinflammatory events, but careful controls for age and strain are required. These animals show morphological changes in their bMyC cell repertoires associated to age, corresponding to an increase in the production of pro-inflammatory cytokines such as IL-1β, which predispose the brain to an enhanced inflammatory response after LPS-systemic challenge.
Do changes in pulse pressure variation and inferior vena cava distensibility during passive leg raising and tidal volume challenge detect preload responsiveness in case of low tidal volume ventilation?
Authors: Taccheri Temistocle , Gavelli Francesco , Teboul Jean-Louis , Shi Rui , Monnet Xavier 
Published: March 2021

Abstract
Background
In patients ventilated with tidal volume (Vt) < 8 mL/kg, pulse pressure variation (PPV) and, likely, the variation of distensibility of the inferior vena cava diameter (IVCDV) are unable to detect preload responsiveness. In this condition, passive leg raising (PLR) could be used, but it requires a measurement of cardiac output. The tidal volume (Vt) challenge (PPV changes induced by a 1-min increase in Vt from 6 to 8 mL/kg) is another alternative, but it requires an arterial line. We tested whether, in case of Vt = 6 mL/kg, the effects of PLR could be assessed through changes in PPV (ΔPPVPLR) or in IVCDV (ΔIVCDVPLR) rather than changes in cardiac output, and whether the effects of the Vt challenge could be assessed by changes in IVCDV (ΔIVCDVVt) rather than changes in PPV (ΔPPVVt).

Methods
In 30 critically ill patients without spontaneous breathing and cardiac arrhythmias, ventilated with Vt = 6 mL/kg, we measured cardiac index (CI) (PiCCO2), IVCDV and PPV before/during a PLR test and before/during a Vt challenge. A PLR-induced increase in CI ≥ 10% defined preload responsiveness.

Results
At baseline, IVCDV was not different between preload responders (n = 15) and non-responders. Compared to non-responders, PPV and IVCDV decreased more during PLR (by − 38 ± 16% and − 26 ± 28%, respectively) and increased more during the Vt challenge (by 64 ± 42% and 91 ± 72%, respectively) in responders. ∆PPVPLR, expressed either as absolute or as percent relative changes, detected preload responsiveness (area under the receiver operating curve, AUROC: 0.98 ± 0.02 for both). ∆IVCDVPLR detected preload responsiveness only when expressed in absolute changes (AUROC: 0.76 ± 0.10), not in relative changes. ∆PPVVt, expressed as absolute or percent relative changes, detected preload responsiveness (AUROC: 0.98 ± 0.02 and 0.94 ± 0.04, respectively). This was also the case for ∆IVCDVVt, but the diagnostic threshold (1 point or 4%) was below the least significant change of IVCDV (9[3–18]%).

Conclusions
During mechanical ventilation with Vt = 6 mL/kg, the effects of PLR can be assessed by changes in PPV. If IVCDV is used, it should be expressed in percent and not absolute changes. The effects of the Vt challenge can be assessed on PPV, but not on IVCDV, since the diagnostic threshold is too small compared to the reproducibility of this variable.
Trial registration: Agence Nationale de Sécurité du Médicament et des Produits de santé: ID-RCB: 2016-A00893-48.
Aedes larval bionomics and implications for dengue control in the paradigmatic Jaffna peninsula, northern Sri Lanka
Authors: Surendran Sinnathamby N. , Jayadas Tibutius T. P. , Thiruchenthooran Vaikunthavasan , Raveendran Selvarajah , Tharsan Annathurai , Santhirasegaram Sharanga , Sivabalakrishnan Kokila , Karunakaran Suthakar , Ponnaiah Bharathy , Gomes Laksiri , Malavige Gathsaurie N. , Ramasamy Ranjan 
Published: March 2021

AbstractBackgroundThe larval bionomics ofAedesacross the Jaffna peninsula in northern Sri Lanka was investigated to obtain information needed for developing more effective larval source reduction measures to control endemic arboviral diseases.MethodsThe habitats of preimaginal stages ofAedesmosquitoes were surveyed, and ovitrap collections were carried out in densely populated areas of the Jaffna peninsula.Aedeslarval productivities were analysed against habitat characteristics, rainfall and dengue incidence. Adults emerging from collected larvae were tested for dengue virus (DENV).ResultsOnlyAedes aegypti,Ae. albopictusandAe. vittatuswere identified in the field habitat collections and ovitraps.Aedes aegyptiwas the predominant species in both the field habitat and ovitrap collections, followed byAe. albopictusand small numbers ofAe. vittatus. Tires and open drains were the preferred field habitats forAe. aegypti, although larval productivity was higher in discarded plastic containers. The threeAedesspecies differed in field habitat preferences. Concomitant presence of the threeAedesspecies was observed in the field habitats and ovitraps. Larval productivities were inversely correlated with the salinity of the field habitat. Rainfall in the preceding month significantly correlated with larval productivity in the field habitats. DENV serotype 2 was detected inAe. aegypticollected from ovitraps in the city of Jaffna. High Breteau, House and Container indices of 5.1, 5.1 and 7.9%, respectively, were observed in the field habitat surveys and ovitrap indices of up to 92% were found in Jaffna city.ConclusionsAedeslarval indices in populated areas of the peninsula showed a high potential for dengue epidemics. Unacceptable littering practices, failure to implement existing dengue control guidelines, vertical transmission of DENV in vector mosquitoes and preimaginal development in brackish water and open surface drains, as well as in domestic wells that provide potable water, are serious constraints to the currentAedeslarval source reduction methods used to control dengue in the Jaffna peninsula. Similar shortcomings in arboviral disease control are likely present in other resource-constrained tropical coastal zones worldwide.Graphical Abstract
Enhancing magnetic resonance imaging-driven Alzheimer’s disease classification performance using generative adversarial learning
Authors: Zhou Xiao , Qiu Shangran , Joshi Prajakta S. , Xue Chonghua , Killiany Ronald J. , Mian Asim Z. , Chin Sang P. , Au Rhoda , Kolachalama Vijaya B. 
Published: March 2021

AbstractBackgroundGenerative adversarial networks (GAN) can produce images of improved quality but their ability to augment image-based classification is not fully explored. We evaluated if a modified GAN can learn from magnetic resonance imaging (MRI) scans of multiple magnetic field strengths to enhance Alzheimer’s disease (AD) classification performance.MethodsT1-weighted brain MRI scans from 151 participants of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), who underwent both 1.5-Tesla (1.5-T) and 3-Tesla imaging at the same time were selected to construct a GAN model. This model was trained along with a three-dimensional fully convolutional network (FCN) using the generated images (3T*) as inputs to predict AD status. Quality of the generated images was evaluated using signal to noise ratio (SNR), Blind/Referenceless Image Spatial Quality Evaluator (BRISQUE) and Natural Image Quality Evaluator (NIQE). Cases from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL,n = 107) and the National Alzheimer’s Coordinating Center (NACC,n = 565) were used for model validation.ResultsThe 3T*-based FCN classifier performed better than the FCN model trained using the 1.5-T scans. Specifically, the mean area under curve increased from 0.907 to 0.932, from 0.934 to 0.940, and from 0.870 to 0.907 on the ADNI test, AIBL, and NACC datasets, respectively. Additionally, we found that the mean quality of the generated (3T*) images was consistently higher than the 1.5-T images, as measured using SNR, BRISQUE, and NIQE on the validation datasets.ConclusionThis study demonstrates a proof of principle that GAN frameworks can be constructed to augment AD classification performance and improve image quality.
RECIST 1.1 and lesion selection: How to deal with ambiguity at baseline?
Authors: Iannessi Antoine , Beaumont Hubert , Liu Yan , Bertrand Anne-Sophie 
Published: March 2021

AbstractResponse Evaluation Criteria In Solid Tumors (RECIST) is still the predominant criteria base for assessing tumor burden in oncology clinical trials. Despite several improvements that followed its first publication, RECIST continues to allow readers a lot of freedom in their evaluations. Notably in the selection of tumors at baseline. This subjectivity is the source of many suboptimal evaluations. When starting a baseline analysis, radiologists cannot always identify tumor malignancy with any certainty. Also, with RECIST, some findings can be deemed equivocal by radiologists with no confirmatory ground truth to rely on. In the specific case of Blinded Independent Central Review clinical trials with double reads using RECIST, the selection of equivocal tumors can have two major consequences: inter-reader variability and modified sensitivity of the therapeutic response. Apart from the main causes leading to the selection of an equivocal lesion, due to the uncertainty of the radiological characteristics or due to the censoring of on-site evaluations, several other situations can be described more precisely. These latter involve cases where an equivocal is selected as target or non-target lesions, the management of equivocal lymph nodes and the case of few target lesions. In all cases, awareness of the impact of selecting a non-malignant lesion will lead radiologists to make selections in the most rational way. Also, in clinical trials where the primary endpoint differs between phase 2 (response-related) and phase 3 (progression-related) trials, our impact analysis will help them to devise strategies for the management of equivocal lesions.
Incidental findings in and around the prostate on prostate MRI: a pictorial review
Authors: Trivedi Janki , Sutherland Tom , Page Mark 
Published: March 2021

AbstractProstate MRI has seen rapid growth in use in recent years as an advanced diagnostic modality to detect focal areas of clinically significant prostate cancer, to identify an area for targeted biopsy and to guide management and surveillance. The increase in use has also led to increased diagnosis of incidental lesions arising from structures around the prostate. These incidental findings may be related to the genitourinary system or non- genitourinary system and may have a benign aetiology which needs no additional follow-up, or it may require surveillance and management. The field of view in a multiparametric prostate MRI includes other pelvic organs, neurovascular bundles, bowel, lymph nodes and bones. Being familiar with standard MRI characteristics and a sound knowledge of anatomy of the prostate and surrounding structures can help in distinguishing normal anatomy from pathology. Given that patients undertaking a prostate MRI are usually a cohort with increased anxiety from their known or suspicion of prostate cancer, it is important that radiologists are familiar with these common incidental findings to minimise anxiety to the patient, have a well-informed discussion with the referring clinician and reduce costs associated with unnecessary further testing and follow-up of benign incidental findings. Additionally, being able to diagnose more serious incidental pathologies early can be life-saving and potentially significantly alter patient management.
Repair abilities of mouse autologous adipose-derived stem cells and ShakeGel™3D complex local injection with intrauterine adhesion by BMP7-Smad5 signaling pathway activation
Authors: Zhao Yun-xia , Chen Shao-rong , Huang Qiao-yi , Chen Wei-can , Xia Tian , Shi Yan-chuan , Gao Hong-zhi , Shi Qi-yang , Lin Shu 
Published: March 2021

Abstract
Background
The objective was to explore the therapeutic effect of autologous adipose-derived stem cells (ADSCs) combined with ShakeGel™3D transplantation to activate the BMP7-Smad5 signaling pathway to treat intrauterine adhesions (IUA).

Methods
Autologous ADSCs were isolated and then merged with ShakeGel™3D. The IUA model was established by mechanical injury. The third generation of autologous ADSCs was injected directly into the uterus in combination with ShakeGel™3D. After 7 days of treatment, endometrial morphology, number of endometrial glands, endometrial fibrosis area, and fibrosis biomarker analysis by RT-PCR and IHC were examined. BMP7 and phosphorylation of Smad5 were also detected, and the recovery of infertility function in treated mice was evaluated.

Results
Fluorescence-activated cell sorting (FACS) showed that autologous ADSCs expressed CD105 (99.1%), CD29 (99.6%), and CD73 (98.9%). Autologous ADSCs could still maintain a good growth state in ShakeGel™3D. Histological examination revealed that the number of endometrial glands increased significantly, and the area of fibrosis decreased. At the same time, the expression of BMP7 and Smad5 in the ADSCs + Gel group was significantly upregulated, and the final reproductive function of this group was partly recovered.

Conclusions
Autologous ADSCs can be used in combination with ShakeGel™3D to maintain functionality and create a viable three-dimensional growth environment. The combined transplantation of autologous ADSCs and ShakeGel™3D promotes the recovery of damaged endometrial tissue by increasing BMP7-Smad5 signal transduction, resulting in endometrium thickening, increased number of glands, and decreased fibrosis, leading to restoration of partial fertility.
GATA-targeted compounds modulate cardiac subtype cell differentiation in dual reporter stem cell line
Authors: Välimäki Mika J. , Leigh Robert S. , Kinnunen Sini M. , March Alexander R. , de Sande Ana Hernández , Kinnunen Matias , Varjosalo Markku , Heinäniemi Merja , Kaynak Bogac L. , Ruskoaho Heikki 
Published: March 2021

Abstract
Background
Pharmacological modulation of cell fate decisions and developmental gene regulatory networks holds promise for the treatment of heart failure. Compounds that target tissue-specific transcription factors could overcome non-specific effects of small molecules and lead to the regeneration of heart muscle following myocardial infarction. Due to cellular heterogeneity in the heart, the activation of gene programs representing specific atrial and ventricular cardiomyocyte subtypes would be highly desirable. Chemical compounds that modulate atrial and ventricular cell fate could be used to improve subtype-specific differentiation of endogenous or exogenously delivered progenitor cells in order to promote cardiac regeneration.

Methods
Transcription factor GATA4-targeted compounds that have previously shown in vivo efficacy in cardiac injury models were tested for stage-specific activation of atrial and ventricular reporter genes in differentiating pluripotent stem cells using a dual reporter assay. Chemically induced gene expression changes were characterized by qRT-PCR, global run-on sequencing (GRO-seq) and immunoblotting, and the network of cooperative proteins of GATA4 and NKX2-5 were further explored by the examination of the GATA4 and NKX2-5 interactome by BioID. Reporter gene assays were conducted to examine combinatorial effects of GATA-targeted compounds and bromodomain and extraterminal domain (BET) inhibition on chamber-specific gene expression.

Results
GATA4-targeted compounds 3i-1000 and 3i-1103 were identified as differential modulators of atrial and ventricular gene expression. More detailed structure-function analysis revealed a distinct subclass of GATA4/NKX2-5 inhibitory compounds with an acetyl lysine-like domain that contributed to ventricular cells (%Myl2-eGFP+). Additionally, BioID analysis indicated broad interaction between GATA4 and BET family of proteins, such as BRD4. This indicated the involvement of epigenetic modulators in the regulation of GATA-dependent transcription. In this line, reporter gene assays with combinatorial treatment of 3i-1000 and the BET bromodomain inhibitor (+)-JQ1 demonstrated the cooperative role of GATA4 and BRD4 in the modulation of chamber-specific cardiac gene expression.

Conclusions
Collectively, these results indicate the potential for therapeutic alteration of cell fate decisions and pathological gene regulatory networks by GATA4-targeted compounds modulating chamber-specific transcriptional programs in multipotent cardiac progenitor cells and cardiomyocytes. The compound scaffolds described within this study could be used to develop regenerative strategies for myocardial regeneration.