bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-421 inhibition protects H9c2 cells against hypoxia/reoxygenation-induced oxidative stress and apoptosis by targeting Sirt3
Authors: Liu Yu , Qian Xi-Ming , He Qi-Cai , Weng Jia-Kan 
Published: August 2019

Background: MicroRNAs (miRNAs) are involved in myocardial ischemia-reperfusion injury. miRNA-421 (miR-421) plays a significant role in the initiation of apoptosis and myocardial infarction. However, the molecular regulation of miR-421 in myocardial ischemia-reperfusion injury requires further elucidation. Methods: An in vitro hypoxia/reoxygenation model was established, and the expression levels of miR-421 and Sirtuin-3 (Sirt3) in H9c2 cells were quantified using quantitative real-time polymerase chain reaction. Flow cytometry was employed to measure the effects of miR-421 on myocardial apoptosis induced by hypoxia/reoxygenation. The activity of lactate dehydrogenase and superoxide dismutase and levels of malondialdehyde were measured. The binding sites of miR-421 on Sirt3 were predicted using TargetScan software. A luciferase reporter assay was used to validate the direct targeting of Sirt3 with miR-421. Protein expression levels of Sirt3 and its downstream proteins were evaluated using Western blot analysis. Results: Exposure of H9c2 cells to hypoxia/reoxygenation led to increased apoptosis, levels of malondialdehyde and lactate dehydrogenase, and decreased levels of superoxide dismutase. miR-421 knockdown resulted in decreased apoptosis, levels of lactate dehydrogenase and malondialdehyde, and increased superoxide dismutase levels in H9c2 cells. Hypoxia/reoxygenation significantly decreased the relative expression levels of Sirt3. Down-regulation of Sirt3 resulted from overexpression of miR-421, which directly targeted Sirt3. Knockdown of miR-421 up-regulated Sirt3 expression, inhibited activation of the Jun N-terminal kinase/activator protein 1 pathway and caspase 9/3-dependent cell death. Conclusion: The miR-421-Sirt3-Jun N-terminal kinase/activator protein 1 axis is a novel molecular mechanism that accommodates hypoxia/reoxygenation-induced oxidative stress and apoptosis and provides a new direction for the study and treatment of hypoxia/reoxygenation.
Selection of systemic therapy in patients with locally advanced and recurrent/metastatic head and neck cancer: RAND-based expert opinion by an Italian multidisciplinary panel
Authors: Benasso Marco , Bonomo Pierluigi , Buglione Michela , Ghi Maria Grazia , Licitra Lisa , Magrini Stefano Maria , Merlano Marco Carlo , Presutti Livio , Ronzino Graziana , Ferrari Daris 
Published: August 2019

Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease often presenting at an already advanced stage. Cisplatin chemoradiotherapy is the standard treatment for locally advanced disease, although its efficacy varies according to different studies. Thus, treatment selection is a challenge, especially in older patients, who frequently have several comorbidities. Moreover, the majority of patients with recurrent and/or metastatic disease are unsuitable for local treatment, either surgery or radiation therapy. The only treatment option for them is systemic therapy, but prognosis remains poor, with a median overall survival of less than 12 months. Methods: A group of Italian key opinion leaders in the field of HNSCC gathered several times in 2018 in order to retrieve a set of statements to help clinicians in their daily decision-making process for the treatment of patients with different scenarios of HNSCC. Results and Conclusion: The panel agreed on 22 statements that were identified as “good clinical points” based on the available literature or after discussion of the most relevant aspect of the underlying diseases when no international consensus was available. The panel identified a number of possible scenarios (namely 71) in which these statements may be helpful to guide decision-making for the best treatment selection.
Meta-analysis of the concordance of Icare® PRO–based rebound and Goldmann applanation tonometry in glaucoma patients
Authors: Rödter Tara Helena , Knippschild Stephanie , Baulig Christine , Krummenauer Frank 
Published: August 2019

Background: The Icare® PRO rebound tonometer is being promoted as a patient-friendly device for glaucoma detection and monitoring, allowing rapid and accurate intraocular pressure measurement avoiding anaesthesia. The aim of this systematic review was to examine the concordance of Icare® PRO and Goldmann applanation tonometry in glaucoma patients. Methods: The German and English literature research was carried out using PubMed and Cochrane Library between January 2010 and March 2018. Method comparison trials in a paired sample study design were identified. Search criteria were ‘Icare PRO’, ‘Rebound’, ‘Goldmann’ and ‘Applanation’. Adult patients with glaucoma of any aetiology were included. The intraindividual intraocular pressure deviation between Icare® PRO and Goldmann applanation tonometry (mm Hg) served as primary endpoint, parameterized by the reported mean differences. For each study, an asymptotic 95% confidence interval was derived. The overall intraocular pressure meta-difference (Icare® PRO-Goldmann applanation tonometry) and 95% confidence interval were estimated using the random effect model. Result: Of 147 publications, 6 studies (672 eyes) were included after reviewing. Four studies showed an intraocular pressure underestimation by the Icare® PRO, two an overestimation. The meta-difference (Icare® PRO-Goldmann applanation tonometry = −0.14 mm Hg; 95% confidence interval: (−0.43 mm Hg; 0.15 mm Hg)) indicated a non-significant, clinically irrelevant mean deviation (p = 0.335). The devices showed good agreement, but there was a strong heterogeneity between the studies (I² = 77%): two studies presented a significant difference (Icare® PRO-Goldmann applanation tonometry), however, with deviations in opposite directions. Conclusion: Although the manufacturer advertises the Icare® PRO as a ‘tonometer with superior accuracy’, the present review could neither confirm nor deny considerable agreement between Goldmann applanation tonometry and Icare® PRO in glaucomatous patients.
Is Access to Care Associated With Stage at Presentation and Survival for Melanoma Patients?
Authors: Pitre Lacey D. , Linford Geordie , Pond Gregory R. , McWhirter Elaine , Seow Hsien 
Published: August 2019

Background Melanoma incidence increases with socioeconomic status but the effect of rurality and access to primary care or dermatology on patient outcomes is unclear. Objectives The objectives of this study were to determine whether access to care, rurality, or socioeconomic status are associated with melanoma stage at presentation and prognosis. Methods Linked administrative databases from Ontario, Canada, were retrospectively analyzed to identify a population-based cohort of patients diagnosed with melanoma between 2004 and 2012. Rurality was assessed using the rural index of Ontario (RIO) score, and the number of visits to dermatology and primary care was used to evaluate access to care. Results We identified 18 776 melanoma patients, of whom 9591 had completed pathological staging. Patients with higher RIO scores, living further from a cancer center or in a rural community, were less likely to see a dermatologist in the year prior to diagnosis ( P < .001 for all). Patients seen by a dermatologist within 365 days prior to diagnosis were less likely to present with stage III or IV disease (odds ratio 0.63, P < .001) and had improved overall survival (hazard ratio [HR] for death 0.77, P < .001). There was a nonlinear association between number of family physician visits and melanoma prognosis, with patients who had 3 to 5 visits per year having the best overall survival (HR 0.88, P = .003). Conclusion Our findings strengthen the known association between access to dermatology and melanoma outcomes by linking individual patients’ prediagnosis access to care to pathological stage at diagnosis and overall survival.
Healthy Weight for Life programme: Evaluating the practice and effectiveness of a weight loss maintenance programme in the private health insurance setting
Authors: McGill Bronwyn , O’Hara Blythe J , Grunseit Anne C , Bauman Adrian , Lawler Luke , Phongsavan Philayrath 
Published: August 2019

Background: Australian private health insurers are increasingly involved in the delivery of chronic disease management programmes to their members, recognising the importance of decreasing and managing lifestyle risk factors and the impact such factors have on health service utilisation. One such secondary prevention programme is the Healthy Weight for Life programme, an intensive weight loss and lifestyle modification programme that has been designed for overweight and obese private health insurance members in Australia. Together with the insurer, the Healthy Weight for Life service provider developed and implemented a long-term maintenance programme that supports participants who complete the Healthy Weight for Life programme to maintain the weight loss they achieved during the programme. Various studies have shown that evidence-based weight management programmes can be effective; however, the results may vary in different contexts. Objective: This article presents the evaluation rationale and framework designed to assess the process and impact of the long-term maintenance programme on weight loss maintenance, other health-related benefits and participants’ experience with the programme. Methods: The evaluation will comprise a number of inter-related sub-studies balancing evaluation of programme effectiveness and implementation. The maintenance programme presented a unique opportunity for researchers to partner with private health insurance and a service provider to assess a real-world programme in the under-researched area of weight loss maintenance in this setting and emphasises the importance of evaluating such programmes given the potential the private health insurance context has in the future delivery of health care.
Striving for a biopsychosocial approach: A secondary analysis of mutual components during healthcare encounters between women with endometriosis and physicians
Authors: Berterö Carina , Alehagen Siw , Grundström Hanna 
Published: August 2019

Objective: The objective of this study was to identify and describe mutual components during healthcare encounters between women with endometriosis and physicians. Methods: Secondary analysis of data was obtained from two original face-to-face interview studies, one with nine women with endometriosis and one including 16 physicians. Data in this secondary analysis were analysed using thematic analysis. Results: Three themes were identified. (1) Continuity as a foundation for a biopsychosocial approach. The women and the physicians described the importance of continuity and both parties strived for a biopsychosocial approach whereby the female body was not treated as biomedical defect object, but as a part of the unity that constitutes a human being. (2) Listening sensitively. Women and physicians believed that listening sensitively involved more than just hearing the actual words – it required thoughtfulness, reflection and responsiveness. (3) Timing of diagnosis. The physicians tried to protect the women from worrying by treating the painful menstruations without mentioning endometriosis. However, the women regarded not mentioning endometriosis as a lack of competence on the part of the physicians. Conclusion: This study provides new insights into the need for further support in the provision of psychosocial care for women with endometriosis, in the striving towards a biopsychosocial approach.
Filamin A: key actor in platelet biology
Authors: Rosa Jean-Philippe , Raslova Hana , Bryckaert Marijke 
Published: August 2019

AbstractFilamins are scaffold proteins for signaling proteins and adhesion molecules, and mutations in filamin A (FLNa) cause a wide range of defects in the brain, cardiovascular system, gastrointestinal tract, and skeleton, as well as in megakaryocytes. Rosa and colleagues review the important role of FLNa in platelet development and its critical importance to proplatelet production by megakaryocytes.
Dose-escalated interleukin-2 therapy for refractory chronic graft-versus-host disease in adults and children
Authors: Whangbo Jennifer S. , Kim Haesook T. , Mirkovic Nikola , Leonard Lauren , Poryanda Samuel , Silverstein Sophie , Kim Soomin , Reynolds Carol G. , Rai Sharmila C. , Verrill Kelly , Lee Michelle A. , Margossian Steven , Duncan Christine , Lehmann Leslie , Huang Jennifer , Nikiforow Sarah , Alyea Edwin P. , Armand Philippe , Cutler Corey S. , Ho Vincent T. , Blazar Bruce R. , Antin Joseph H. , Soiffer Robert J. , Ritz Jerome , Koreth John 
Published: August 2019

AbstractLow-dose interleukin-2 (IL-2) therapy for chronic graft-versus-host disease (cGVHD) generates a rapid rise in plasma IL-2 levels and CD4+CD25+CD127−Foxp3+ regulatory T-cell (CD4Treg) proliferation, but both decrease over time despite continued daily administration. To test whether IL-2 dose escalation at the time of anticipated falls in plasma levels could circumvent tachyphylaxis and enhance CD4Treg expansion, we conducted a phase 1 trial in 10 adult and 11 pediatric patients with steroid-refractory cGVHD (www.clinicaltrials.gov: NCT02318082). Daily IL-2 was initiated in children and adults (0.33 × 106 and 0.67 × 106 IU/m2 per day, respectively). Dose escalations were scheduled at weeks 2 and 4 to a maximum dose of 1 × 106 IU/m2 per day in children and 2 × 106 IU/m2 per day in adults. Patients continued at their maximum tolerated dose (MTD) until week 8. Children tolerated IL-2 dose escalation with partial responses (PRs) in 9 of 11 patients (82%) at multiple cGVHD sites, including lung. Patient-reported outcome scores for skin and lung improved significantly in pediatric patients. In contrast, 5 of 10 adults required dose reduction, and only 2 of 7 evaluable patients (29%) had PRs at week 8. CD4Tregs and natural killer cells expanded in both cohorts without significant changes in conventional CD4+ T cells (Tcons) or CD8+ T cells. Children achieved a higher median CD4Treg/Tcon ratio at week 8 (0.4 vs 0.18, P = .02) despite lower IL-2 doses. We show for the first time that low-dose IL-2 is safe and effective in children with advanced cGVHD. In adults, escalation above the previously defined MTD did not improve CD4Treg expansion or clinical response.
A novel tumor suppressor protein encoded by circular AKT3 RNA inhibits glioblastoma tumorigenicity by competing with active phosphoinositide-dependent Kinase-1
Authors: Xia Xin , Li Xixi , Li Fanying , Wu Xujia , Zhang Maolei , Zhou Huangkai , Huang Nunu , Yang Xuesong , Xiao Feizhe , Liu Dawei , Yang Lixuan , Zhang Nu 
Published: August 2019

Abstract
Background
The RTK/PI3K/AKT pathway plays key roles in the development and progression of many cancers, including GBM. As a regulatory molecule and a potential drug target, the oncogenic role of AKT has been substantially studied. Three isoforms of AKT have been identified, including AKT1, AKT2 and AKT3, but their individual functions in GBM remain controversial. Moreover, it is not known if there are more AKT alternative splicing variants.

Methods
High-throughput RNA sequencing and quantitative reverse transcription-PCR were used to identify the differentially expressed circRNAs in GBM samples and in paired normal tissues. High throughput RNA sequencing was used to identify circ-AKT3 regulated signaling pathways. Mass spectrometry, western blotting and immunofluorescence staining analyses were used to validate AKT3-174aa expression. The tumor suppressive role of AKT3-174aa was validated in vitro and in vivo. The competing interaction between AKT3-174aa and p-PDK1 was investigated by mass spectrometry and immunoprecipitation analyses.

Results
Circ-AKT3 is a previously uncharacterized AKT transcript variant. Circ-AKT3 is expressed at low levels in GBM tissues compared with the expression in paired adjacent normal brain tissues. Circ-AKT3 encodes a 174 amino acid (aa) novel protein, which we named AKT3-174aa, by utilizing overlapping start-stop codons. AKT3-174aa overexpression decreased the cell proliferation, radiation resistance and in vivo tumorigenicity of GBM cells, while the knockdown of circ-AKT3 enhanced the malignant phenotypes of astrocytoma cells. AKT3-174aa competitively interacts with phosphorylated PDK1, reduces AKT-thr308 phosphorylation, and plays a negative regulatory role in modulating the PI3K/AKT signal intensity.

Conclusions
Our data indicate that the impaired circRNA expression of the AKT3 gene contributes to GBM tumorigenesis, and our data corroborate the hypothesis that restoring AKT3-174aa while inhibiting activated AKT may provide more benefits for certain GBM patients.
Physical Performance Measures Correlate with Head Impact Exposure in Youth Football
Authors: KELLEY MIREILLE E. , JONES DEREK A. , ESPELAND MARK A. , ROSENBERG MEAGAN L. , MILES CHRISTOPHER M. , WHITLOW CHRISTOPHER T. , MALDJIAN JOSEPH A. , STITZEL JOEL D. , URBAN JILLIAN E. 
Published: August 2019

ABSTRACT

Purpose
Head impact exposure (HIE) (i.e., magnitude and frequency of impacts) can vary considerably among individuals within a single football team. To better understand individual-specific factors that may explain variation in head impact biomechanics, this study aimed to evaluate the relationship between physical performance measures and HIE metrics in youth football players.

Methods
Head impact data were collected from youth football players using the Head Impact Telemetry System. Head impact exposure was quantified in terms of impact frequency, linear and rotational head acceleration, and risk-weighted cumulative exposure metrics (RWELinear, RWERotational, and RWECP). Study participants completed four physical performance tests: vertical jump, shuttle run, three-cone, and 40-yard sprint. The relationships between performance measures, and HIE metrics were evaluated using linear regression analyses.

Results
A total of 51 youth football athletes (ages, 9–13 yr) completed performance testing and received combined 13,770 head impacts measured with the Head Impact Telemetry System for a full season. All performance measures were significantly correlated with total number of impacts in a season, RWELinear-Season, and all RWE-Game metrics. The strongest relationships were between 40-yard sprint speed and all RWE-Game metrics (all P ≤ 0.0001 and partial R
2 > 0.3). The only significant relationships among HIE metrics in practice were between shuttle run speed and total practice impacts and RWELinear-Practices, 40 yard sprint speed and total number of practice impacts, and three-cone speed and 95th percentile number of impacts/practice.

Conclusions
Generally, higher vertical jump height and faster times in speed and agility drills were associated with higher HIE, especially in games. Physical performance explained less variation in HIE in practices, where drills and other factors, such as coaching style, may have a larger influence on HIE.
Bone islands incidentally detected on computed tomography: frequency of enostosis and differentiation from untreated osteoblastic metastases based on CT attenuation value
Authors: Sala Francesco , Dapoto Annarita , Morzenti C. , firetto Maria cristina , Valle Clarissa , Tomasoni A. , Sironi Sandro 
Published: August 2019

Objective: The frequency of enostosis incidentally found on CT and CT attenuation value to distinguish them from untreated osteoblastic metastases (UOM). Methods: Enostosis group: 46 polytrauma patients underwent thoracoabdominal CT. Inclusion criteria: age range 14–35 years. Exclusion criteria: cancer, previous fractures. UOM group: 20 patients with radiological diagnosis of UOM. Analyzed data: number, size, location and density of enostoses and metastases. The density was measured with the broadest possible region of interest at the center of the lesion by two radiologists independently. Receiver operatingcharacteristic analysis to determine the sensitivity and specificity, area under the curve 95% confidence intervals and cutoff values of CT density to differentiate metastases from enostoses. Results: Patients were 28 ± 7 years old (72% males). 41 (89%) patients had 124 enostoses (2–15 mm) with an average density of 1007 ± 122 Hounsfiled unit (HU, observer1) and 1052 ± 107 (observer2). The most common sites of occurrence were the proximal femur (34%), the pelvis (22%), the acetabulum (20%), the proximal humerus (11%), the vertebrae (11%) and the rib (2%). 13 patients had 1 bone island, 8 patients had 2, 9 cases had 3 and 11 cases had more than 3 enostoses. Overall, 114 UOM were evaluated, their average density was 728 ± 163 HU (observer1) and 712 ± 178 HU (observer2). The area under the curve value of mean density to distinguish enostoses from UOM was 0,982. Using a cut-off of 881 HU for mean density, sensitivity was 98% and specificity 95%. Conclusion: The frequency of enostosis in this study is 89%. The average density identified can help to distinguish enostoses from UOM. Advances in knowledge: We report the exact frequency of enostosis.
Registration accuracy with the low dose kilovoltage cone-beam CT: A phantom study
Authors: Takei Yoshiki , Monzen Hajime , Matsumoto Kenji , Hanaoka Kohei , Tamura Mikoto , Nishimura Yasumasa 
Published: August 2019

Objective: The aim of this study was to investigate low-dose kilovoltage cone-beam CT (kV-CBCT) for image-guided radiotherapy, with a particular focus on the accuracy of image registration with low-dose protocols. Methods: Imaging doses were measured with a NOMEX semiconductor detector positioned at the front of head, thorax, and pelvis human body phantoms while kV-CBCT scans were acquired at different tube currents. Aspects of image quality (spatial resolution, noise, uniformity, contrast, geometric distortion, and Hounsfield unit sensitivity) and image registration accuracy using bone and soft tissue were evaluated. Results: With preset and the lowest tube currents, the imaging doses were 0.16 and 0.08 mGy, 5.29 and 2.80 mGy, and 18.23 and 2.69 mGy for head, thorax, and pelvis, respectively. Noise was the only quality aspect directly dependent on tube current, being increased by 1.5 times with a tube current half that of the preset in head and thorax, and by 2.2 times with a tube current 1/8 of the preset in the pelvis. Accurate auto-bone matching was performed within 1 mm at the lowest tube current. The auto-soft tissue matching could not be performed with the lowest tube current; however, manual-soft tissue matching could still be performed within 2 mm or less. Conclusion: Noise was the only image quality aspect dependent on the imaging dose. Auto-bone and manual-soft tissue matching could still be performed at the lowest imaging dose. Advances in knowledge: When optimizing kV-CBCT imaging dose, the impact on bone and soft tissue image registration accuracy should be evaluated.