bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Multidisciplinary Team Management on the Survival Rate of Head and Neck Cancer Patients: A Cohort Study Meta-analysis
Authors: Shang Changyi , Feng Linfei , Gu Ying , Hong Houlin , Hong Lilin , Hou Jun 
Published: March 2021

Background: Head and neck cancer (HNC) is one of the more common malignant tumors that threaten human health worldwide. Multidisciplinary team management (MDTM) in HNC treatment has been introduced in the past several decades to improve patient survival rates. This study reviewed the impact of MDTM on survival rates in patients with HNC compared to conventional treatment methods.Methods: Only cohort studies were identified for this meta-analysis that included an exposure group that utilized MDTM and a control group. Heterogeneity and sensitivity also were assessed. Survival rate data for HNC patients were analyzed using RevMan 5.2 software.Results: Five cohort studies (n = 39,070) that examined survival rates among HNC patients were included. Hazard ratios (HR) were calculated using the random effect model. The results revealed that exposure groups treated using MDTM exhibited a higher survival rate [HR = 0.84, 95% CI (0.76–0.92), P = 0.0004] with moderate heterogeneity (I2 = 68%, p = 0.01). For two studies that examined the effect of MDTM on the survival rate for patients specifically with stage IV HNC, MDTM did not produce any statistically significant improvement in survival rates [HR = 0.81, 95% CI (0.59–1.10), p = 0.18].Conclusions: The application of MDTM based on conventional surgery, radiotherapy, and chemotherapy improved the overall survival rate of patients with HNC. Future research should examine the efficacy of MDTM in patients with cancer at different stages.
Exploration of an Integrative Prognostic Model of Radiogenomics Features With Underlying Gene Expression Patterns in Clear Cell Renal Cell Carcinoma
Authors: Huang Yeqian , Zeng Hao , Chen Linyan , Luo Yuling , Ma Xuelei , Zhao Ye 
Published: March 2021

BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common malignancies in urinary system, and radiomics has been adopted in tumor staging and prognostic evaluation in renal carcinomas. This study aimed to integrate image features of contrast-enhanced CT and underlying genomics features to predict the overall survival (OS) of ccRCC patients.MethodWe extracted 107 radiomics features out of 205 patients with available CT images obtained from TCIA database and corresponding clinical and genetic information from TCGA database. LASSO-COX and SVM-RFE were employed independently as machine-learning algorithms to select prognosis-related imaging features (PRIF). Afterwards, we identified prognosis-related gene signature through WGCNA. The random forest (RF) algorithm was then applied to integrate PRIF and the genes into a combined imaging-genomics prognostic factors (IGPF) model. Furthermore, we constructed a nomogram incorporating IGPF and clinical predictors as the integrative prognostic model for ccRCC patients.ResultsA total of four PRIF and four genes were identified as IGPF and were represented by corresponding risk score in RF model. The integrative IGPF model presented a better prediction performance than the PRIF model alone (average AUCs for 1-, 3-, and 5-year were 0.814 vs. 0.837, 0.74 vs. 0.806, and 0.689 vs. 0.751 in test set). Clinical characteristics including gender, TNM stage and IGPF were independent risk factors. The nomogram integrating clinical predictors and IGPF provided the best net benefit among the three models.ConclusionIn this study we established an integrative prognosis-related nomogram model incorporating imaging-genomic features and clinical indicators. The results indicated that IGPF may contribute to a comprehensive prognosis assessment for ccRCC patients.
Fisetin Attenuates Myocardial Ischemia-Reperfusion Injury by Activating the Reperfusion Injury Salvage Kinase (RISK) Signaling Pathway
Authors: Shanmugam Karthi , Boovarahan Sri Rahavi , Prem Priyanka , Sivakumar Bhavana , Kurian Gino A 
Published: March 2021

Ischemia-reperfusion (I/R) injury is an unavoidable injury that occurs during revascularization procedures. In the previous study, we reported that fisetin is a natural flavonoid that attenuates I/R injury by suppressing mitochondrial oxidative stress and mitochondrial dysfunction. Though fisetin is reported as a GSK3β inhibitor, it remains unclear whether it attenuates myocardial ischemia by activating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, thereby inhibiting the downstream GSK3β, or by directly interacting with GSK3β while rendering its cardioprotection. In this study, the research team investigates the possible mechanism of action of fisetin while rendering its cardioprotective effect against myocardial I/R injury in rats. For this investigation, the team utilized two myocardial I/R models: Ligation of the left anterior descending artery and Langendorff isolated heart perfusion system. The latter has no neurohormonal influences. The PI3K inhibitor (Wortmannin, 0.015 mg/kg), GSK3β inhibitor (SB216763, 0.7 mg/kg), and fisetin (20 mg/kg) were administered intraperitoneally before inducing myocardial I/R. The result of this study reveals that the administration of fisetin decreases the myocardial infarct size, apoptosis, lactate dehydrogenase, and creatine kinase in serum\perfusate of the rat hearts subjected to I/R. However, the inhibition of PI3K with Wortmannin significantly reduced the cardioprotective effect of fisetin both in the ex vivo and vivo models. The administration of GSK3β inhibitor after the administration of fisetin and Wortmannin, re-establishing the cardioprotection, indicates the major role of PI3K in fisetin action. Changes in myocardial oxidative stress (level) and mitochondrial functional preservation of interfibrillar and subsarcolemmal mitochondria support the above findings. Hence, the team here reports that fisetin conferred its cardioprotection against I/R injury by activating the PI3K/Akt/GSK3β signaling pathway in rat hearts.
Mitochondrial Function, Fatty Acid Metabolism, and Body Composition in the Hyperbilirubinemic Gunn Rat
Authors: Vidimce Josif , Pillay Johara , Shrestha Nirajan , Dong Lan-feng , Neuzil Jiri , Wagner Karl-Heinz , Holland Olivia Jane , Bulmer Andrew Cameron 
Published: March 2021

Background: Circulating bilirubin is associated with reduced adiposity in human and animal studies. A possible explanation is provided by in vitro data that demonstrates that bilirubin inhibits mitochondrial function and decreases efficient energy production. However, it remains unclear whether hyperbilirubinemic animals have similar perturbed mitochondrial function and whether this is important for regulation of energy homeostasis.Aim: To investigate the impact of unconjugated hyperbilirubinemia on body composition, and mitochondrial function in hepatic tissue and skeletal muscle.Materials and Methods: 1) Food intake and bodyweight gain of 14-week old hyperbilirubinemic Gunn (n = 19) and normobilirubinemic littermate (control; n = 19) rats were measured over a 17-day period. 2) Body composition was determined using dual-energy X-ray absorptiometry and by measuring organ and skeletal muscle masses. 3) Mitochondrial function was assessed using high-resolution respirometry of homogenized liver and intact permeabilized extensor digitorum longus and soleus fibers. 4) Liver tissue was flash frozen for later gene (qPCR), protein (Western Blot and citrate synthase activity) and lipid analysis.Results: Female hyperbilirubinemic rats had significantly reduced fat mass (Gunn: 9.94 ± 5.35 vs. Control: 16.6 ± 6.90 g, p &lt; 0.05) and hepatic triglyceride concentration (Gunn: 2.39 ± 0.92 vs. Control: 4.65 ± 1.67 mg g−1, p &lt; 0.01) compared to normobilirubinemic controls. Furthermore, hyperbilirubinemic rats consumed fewer calories daily (p &lt; 0.01) and were less energetically efficient (Gunn: 8.09 ± 5.75 vs. Control: 14.9 ± 5.10 g bodyweight kcal−1, p &lt; 0.05). Hepatic mitochondria of hyperbilirubinemic rats demonstrated increased flux control ratio (FCR) via complex I and II (CI+II) (Gunn: 0.78 ± 0.16 vs. Control: 0.62 ± 0.09, p &lt; 0.05). Similarly, exogenous addition of 31.3 or 62.5 μM unconjugated bilirubin to control liver homogenates significantly increased CI+II FCR (p &lt; 0.05). Hepatic PGC-1α gene expression was significantly increased in hyperbilirubinemic females while FGF21 and ACOX1 was significantly greater in male hyperbilirubinemic rats (p &lt; 0.05). Finally, hepatic mitochondrial complex IV subunit 1 protein expression was significantly increased in female hyperbilirubinemic rats (p &lt; 0.01).Conclusions: This is the first study to comprehensively assess body composition, fat metabolism, and mitochondrial function in hyperbilirubinemic rats. Our findings show that hyperbilirubinemia is associated with reduced fat mass, and increased hepatic mitochondrial biogenesis, specifically in female animals, suggesting a dual role of elevated bilirubin and reduced UGT1A1 function on adiposity and body composition.
The Protective Effects of Shengmai Formula Against Myocardial Injury Induced by Ultrafine Particulate Matter Exposure and Myocardial Ischemia are Mediated by the PI3K/AKT/p38 MAPK/Nrf2 Pathway
Authors: Chen Lina , Guo Yuan , Qu Shuiqing , Li Kai , Yang Ting , Yang Yuanmin , Zheng Zhongyuan , Liu Hui , Wang Xi , Deng Shuoqiu , Zhang Yu , Zhu Xiaoxin , Li Yujie 
Published: March 2021

Background and Purpose: Ultrafine particulate matter (UFPM) induces oxidative stress (OS) and is considered to be a risk factor of myocardial ischemia (MI). Shengmai formula (SMF) is a traditional Chinese medicine with antioxidant properties and has been used to treat cardiovascular diseases for a long time. The aim of this study was to explore the protective role of SMF and the mechanism by which it prevents myocardial injury in UFPM-exposed rats with MI.Methods: An MI rat model was established. Animals were randomly divided into five groups: sham, UFPM + MI, SMF (1.08 mg/kg⋅d) + UFPM + MI, SMF (2.16 mg/kg⋅d) + UFPM + MI, and SMF (4.32 mg/kg⋅d) + UFPM + MI. SMF or saline was administrated 7 days before UFPM instillation (100 μg/kg), followed by 24 h of ischemia. Physiological and biochemical parameters were measured, and histopathological examinations were conducted to evaluate myocardial damage. We also explored the potential mechanism of the protective role of SMF using a system pharmacology approach and an in vitro myoblast cell model with small molecule inhibitors.Results: UFPM produced myocardial injuries on myocardial infarct size; serum levels of LDH, CK-MB, and cardiac troponin; and OS responses in the rats with MI. Pretreatment with SMF significantly attenuated these damages via reversing the biomarkers. SMF also improved histopathology induced by UFPM and significantly altered the PI3K/AKT/MAPK and OS signaling pathways. The expression patterns of Cat, Gstk1, and Cyba in the UFPM model group were reversed in the SMF-treated group. In in vitro studies, SMF attenuated UFPM-induced reactive oxygen species production, mitochondrial damage, and OS responses. The PI3K/AKT/p38 MAPK/Nrf2 pathway was significantly changed in the SMF group compared with that in the UFPM group, whereas opposite results were obtained for pathway inhibition.Conclusion: These findings indicate that SMF prevents OS responses and exerts beneficial effects against myocardial injury induced by UFPM + MI in rats. Furthermore, the PI3K/AKT/p38 MAPK/Nrf2 signaling pathway might be involved in the protective effects of SMF.
A Prospective Study of Vitamin D Supplement in Thyroidectomy Patients Based on Relative Decline of Parathyroid Hormone
Authors: Hao Qing , Qin Yun , Zhao Wanjun , Zhang Lingyun , Luo Han 
Published: March 2021

Background: In postthyroidectomy patients, hypocalcemia is the most common complication to prolong hospital stay and decrease patients’ satisfaction. Based on current evidence, it is recommended to supply vitamin D to patients with high risk of developing hypocalcemia. However, how to stratify the risk of patients remains challenging.Aim: We conducted a prospective study to evaluate the effect of vitamin D supplement (calcitriol) on high-risk hypocalcemia patients based on relative decline of parathyroid hormone (RDP).Method: RDP was calculated by the difference between preoperative and postoperative first-day PTH divided by preoperative PTH and presented as percentage. Patients who underwent total thyroidectomy in addition to bilateral central compartment dissection were enrolled prospectively and were divided into two cohorts: Cohort I: patients with RDP ≤70% and Cohort II: patients with RDP &gt;70%. Patients in Cohort I were then randomly assigned to Group A or B, and patients in Cohort II were randomly assigned to Group C or D. All groups received oral calcium, and patients in Groups B and D also received calcitriol. All patients were followed for one year. In the study, standard procedure dictates that only oral calcium is given to patients whose RDP ≤70% and that oral calcium and calcitriol are given to patients whose RDP &gt;70%. Therefore, Cohort I Group A and Cohort II Group D are controls in this study.Results: The incidence of clinical hypocalcemia in Groups A and D (the controls) was 11.0% (10/91), and 17.6% (16/91) required additional intravenous calcium. Of note, no patients developed permanent hypocalcemia. Furthermore, calcitriol supplement did not have significant impact on clinical outcomes between Group A and B in Cohort I. By contrast, calcitriol supplement distinctly improved clinical outcome by comparing Groups C and D (Cohort II), as marked by clinical hypocalcemia, need of requiring intravenous calcium, and long-termed decreased levels of PTH.Conclusion: Supplying calcitriol based on RDP cutoff of 70% may be a wise practice in thyroidectomy patients, and RDP 70% may be a useful predictor to stratify high-risk patients.
LINC01116 Promotes Doxorubicin Resistance in Osteosarcoma by Epigenetically Silencing miR-424-5p and Inducing Epithelial-Mesenchymal Transition
Authors: Li Ran , Ruan Qing , Zheng Jia , Zhang Butian , Yang Hongliang 
Published: March 2021

Background: Development of resistance to doxorubicin-based chemotherapy limits its curative effect in osteosarcoma. In the current study, we focused on investigating the mechanisms underlying the development of doxorubicin resistance in osteosarcoma.Methods: The human osteosarcoma cell line MG-63 and doxorubicin-resistant MG-63/Dox cells were used in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of the long non-coding RNA LINC01116 in the two cell lines. Then, the specific shRNA for LINC01116 was employed to suppress LINC01116 expression in MG-63/Dox cells. Cell viability was assessed by the CCK-8 and colony formation assays. Cell migration and invasion were evaluated by the transwell assay. Moreover, the epithelial-mesenchymal transition (EMT)-related proteins, E-cadherin, vimentin, and N-cadherin were evaluated by Western blotting. The regulation of LINC01116 on miR-424-5p expression was examined using methylation-specific PCR, RNA immunoprecipitation, and Western blotting assay. The potential targeting of HMGA2 by miR-424-5p was predicted using the bioinformatics databases TargetScan and miRanda and verified by a dual-luciferase reporter assay.Results: LINC01116 was more highly expressed in MG-63/Dox cells than in MG-63 cells. Inhibition of LINC01116 suppressed cell viability, migration, and invasion, along with upregulating the expression of E-cadherin, downregulating vimentin, and attenuating doxorubicin resistance in MG-63/Dox cells. Further mechanism-related investigations indicated that LINC01116 regulated HMGA2 expression via the EZH2-associated silencing of miR-424-5p.Conclusion: LINC01116 exerts regulatory effects on doxorubicin resistance through the miR-424-5p axis, providing a potential approach to overcoming chemoresistance in osteosarcoma.
Assessment of Secular Trends and Health Risk in Pediatric Cardiorespiratory Fitness From the Republic of Slovenia
Authors: Morrison Shawnda A. , Sember Vedrana , Leskošek Bojan , Kovač Marjeta , Jurak Gregor , Starc Gregor 
Published: March 2021

ObjectivesDetermine the temporal trends in cardiorespiratory fitness (CRF) and health risk of Slovenian schoolchildren across a 20-year span, assessed via 20-m shuttle run (20mSRT), including defining centile ranges and possible health risk(s) for each generation.MethodsNationally representative data from 9,426 healthy schoolchildren (6–14 years old) were used to determine changes in CRF across three generations, in 1993 (n = 3,174), 2003 (n = 3,457) and 2013 (n = 2,795) from a multistage, stratified, decennial study.Results20mSRT performance declined ∼2.8% from 1993 to 2003, independent of age or sex of the child. This trend was reversed in 2013, increasing by ∼8.2% across all age groups, for both girls and boys, for a net increase of 5.4%. The magnitude of improvement was similar for both sexes. Moreover, girls in the 2013 generation (for ages 10–13 year) completed more stages than their 2003 male counterparts. Across all generations, children achieved CRF values corresponding to low cardiovascular risk for future health outcomes. Centile values ranged from “low” to “very high” depending on age, sex, and generation of the sample.ConclusionNegative trends in CRF from Slovenian schoolchildren were reversed by 2013, indicating that Slovenia should continue implementing progressive national physical fitness strategies introduced between sampling periods (i.e., 2003–2013). Additionally, due to the universal nature of Slovenian schoolchildren achieving “healthy cut-off values” for 20mSRT (generation-inclusive), it is suggested that more specific cut-off criteria are developed, especially for younger children, and girls, so that future CRF results can be more accurately applied for both clinical and pedagogical users.
Protocol for a Phase Two, Parallel Three-Armed Non-inferiority Randomized Controlled Trial of Acceptance and Commitment Therapy (ACT-Adjust) Comparing Face-to-Face and Video Conferencing Delivery to Individuals With Traumatic Brain Injury Experiencing Psychological Distress
Authors: Whiting Diane L. , Simpson Grahame K. , Deane Frank P. , Chuah Sarah L. , Maitz Michelle , Weaver Jerre 
Published: March 2021

Background: People with traumatic brain injury (TBI) face a range of mental health challenges during the adjustment process post-injury, but access to treatment can be difficult, particularly for those who live in regional and remote regions. eHealth provides the potential to improve access to evidence-based psychological therapy for people with a severe TBI. The aim of the current study is to assess the efficacy of a psychological intervention delivered via video consulting to reduce psychological distress in people with TBI.Methods: This paper outlines the protocol for a multi-center, three-arm, parallel, non-inferiority randomized controlled trial (RCT) of an evidence-based manualized psychological intervention, ACT-Adjust. ACT-Adjust provides nine sessions for adults with a moderate to severe TBI experiencing clinical levels of psychological distress. Fifty-six participants referred from Brain Injury Rehabilitation Units across New South Wales (NSW) and the NSW icare scheme will be randomly allocated to three conditions; (1) video consulting (VC), (2) face-to-face (FtF) and, (3) a waitlist control (WL).Discussion: This is the first RCT to evaluate the efficacy of a psychological therapy (ACT-Adjust) delivered via video consulting for individuals with a moderate to severe TBI.Trial Registration:www.anzctr.org.au, Australian New Zealand Clinical Trials Registry ANZCTRN2619001602112.
A Novel Sampling Model to Study the Epidemiology of Canine Leishmaniasis in an Urban Environment
Authors: Parker Lucy A. , Acosta Lucrecia , Gutierrez Mariana Noel , Cruz Israel , Nieto Javier , Deschutter Enrique Jorge , Bornay-Llinares Fernando Jorge 
Published: March 2021

Background: Visceral leishmaniasis (VL) is one of the most important parasitic diseases in the world. The domestic dog is the main reservoir of zoonotic VL and a high prevalence of canine leishmaniasis (CanL) is associated with transmission of infection to humans. Here we describe the methodology used to obtain a rapid and representative sample of domestic dogs in the city of Posadas, Misiones, and compare the prevalence of Leishmania infection with a sample of shelter dogs.Methodology: We used the city land registry to make a random selection of homes and systematically recruited 349 domestic dogs from the selected properties. We also included all dogs from the main canine shelter within the city. Dogs were examined by two experienced veterinarians who recorded the presence of clinical signs common in CanL using a standardized protocol. We extracted a blood sample from each dog and performed four different serological tests to reveal the presence of anti-Leishmania antibodies.Results: After clinical examination, 145 domestic dogs (41.5%) and 63 (90%) shelter dogs had clinical signs compatible with CanL (p &lt; 0.001). The seroprevalence among domestic dogs was 20.1% (95% CI 16.1–24.6) which was significantly lower than among the abandoned dogs (38.6%, 95% CI 27.7–50.6, p &lt; 0.001). The spatial distribution of infected dogs was fairly homogenous throughout the city. Among domestic dogs, we observed a positive association between where the dog slept and presence of anti-Leishmania antibodies (p = 0.034). Of the seropositive domestic dogs 38 (54.4%) were asymptomatic.Conclusions: Our findings demonstrate how seroprevalence results can be highly influenced by sampling methodology. We demonstrate how the land registry can be used to estimate the prevalence of CanL in representative sample of domestic dogs in an urban setting, allowing decision makers to deepen their understanding the epidemiology of CanL in a timely and efficient manner for the development of plans to address both human and canine disease.