bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-29a mitigation of endoplasmic reticulum and autophagy aberrance counteracts in obstructive jaundice-induced fibrosis in mice
Authors: Huang Ying-Hsien , Yang Ya-Ling , Huang Fu-Chen , Tiao Mao-Meng , Lin Yen-Cheng , Tsai Ming-Horng , Wang Feng-Sheng 
Published: November 2017

Hepatic fibrosis was caused by a number of signaling pathways that damage liver integrity. We have previously shown that microRNA-29a (miR-29a) protects against liver fibrosis. Aberrant endoplasmic reticulum (ER) and autophagy function reportedly exaggerate hepatic disorders. The aim of this study was to characterize the biological influence of miR-29a on ER function in injured livers with bile duct ligation (BDL). We performed BDL on miR-29a transgenic mice (miR-29aTg) and wild-type mice to induce cholestatic liver injury. Rat T6 cells were transfected with miR-29a mimic and tunicamycin. Compared to the wild-type mice, the BDL deterioration of liver function in terms of total bilirubin, alanine transaminase, and aspartate transaminase activity in the miR-29aTg mice was significantly reduced. Affected livers in the miR-29aTg mice demonstrated a slight fibrotic matrix formation. miR-29a over-expression reduced the BDL disturbance of the expressions of inositol-requiring kinase 1alpha, double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase, spliced-X-box binding protein 1 (sXBP1), CCAAT/enhancer-binding protein homologous protein (CHOP), ULK, LC3BII, p62, and cleaved caspase-8, 9 and 3. In vitro, T6 cells exposed to tunicamycin by increasing abundances of CHOP, sXBP1, cleaved caspase-3, and LC3BII were diminished in the cell cultures transfected with the miR-29a mimic. On the other hand, we observed that miR-29a signaling protected liver tissues from BDL-mediated metabolic dysfunction and excessive fibrosis histopathology. This study provides new molecular insight into the miR-29a stabilization of ER integrity that slows the progression of cholestatic liver deterioration. Impact statement Long-term hepatic damage caused by hepatitis and cholestasis can accelerate fibrosis matrix over-production, which is a harmful process attributed to the dysregulation of a number of cellular and molecular events. The purpose of this study is to characterize the biological influence of miR-29a on endoplasmic reticulum (ER) function in bile duct ligation (BDL)-injured livers. To the best of our knowledge, this report is the first demonstration that miR-29a over-expression diminishes BDL provocation of ER stress (unfolded protein response, UPR) effector protein expression. This work also demonstrates that miR-29a decreased caspases protein expression in cholestatic livers, while an increase in miR-29a function reduced sXBP1 and CHOP expressions in T6 cells in mice. Analyses of this study highlight that controlling miR-29a signaling can serve as an innovative strategy in the future for microRNA regulation of ER homeostasis to combat cholestasis induction hepatic disorders.
Results of scaphocapitate arthrodesis with lunate excision in advanced Kienböck disease at 10.7-year mean follow-up
Authors: Charre Amaury , Delclaux Stephanie , Apredoai Costel , Ayel Jean-Emmanuel , Rongieres Michel , Mansat Pierre 
Published: November 2017

Scaphocapitate arthrodesis with lunate excision was performed for treatment of advanced Kienböck disease in 17 patients (18 wrists). Ten were women and seven men. Five were Lichtmann Stage IIIA, 12 Stage IIIB, and one Stage IV. Minimum follow-up period was 24 months; mean follow-up was 10.7 years (range 2.3 to 22 years, SD 7.1). At the latest follow-up, six patients were very satisfied, nine were satisfied and two were disappointed. Pain was significantly decreased in all cases. Wrist mobility was unchanged. Grip strength was significantly increased. Consolidation of the arthrodesis was confirmed in 17 wrists. We encountered a scaphocapitate nonunion at 12 years follow-up and two cases of styloscaphoid arthritis at 17 and 22 years. Scaphocapitate arthrodesis with lunate excision performed in an advanced stage of Kienböck disease significantly alleviates pain, while preserving functional mobility and satisfactory grip strength in the long term. Level of evidence: IV
Swan neck deformity due to chronic radial collateral ligament injury of the little finger proximal interphalangeal joint
Authors: Hamada Yoshitaka , Takai Hiroaki , Satoh Ryousuke , Hibino Naohito , Ueda Yukiko , Minamikawa Yoshitaka 
Published: November 2017

We present seven cases of a relatively rare swan neck deformity resulting from chronic radial collateral ligament (RCL) injury of the proximal interphalangeal (PIP) joint in the little finger. All patients were middle-aged women (mean 51 years old, range 42–55), and the duration between the initial injury and surgery was 20 years (range 5–40). The chief complaint was painful snapping of the PIP joint. All patients had hyperextension and ulnar deviation of the PIP joint with mobile swan neck deformities that had not improved with conservative treatment. Radiographs revealed osteoarthritis and ulnar deviation of the PIP joints in all cases. We describe a method for reconstruction of both the palmar plate and the RCL of the affected PIP joint using a distally-based ulnar slip of flexor superficialis tendon. The prevention of PIP joint hyperextension was critical for successful resolution of symptoms; the aim of RCL augmentation was to prevent the recurrence of the deformity. Level of evidence: IV
The combined shoulder assessment: a convenient method for obtaining equivalent outcome scores
Authors: Torrance Emma , Hallam Linda , Walton Michael J. , Monga Puneet , Watts Adam C. , Funk Lennard 
Published: November 2017

Background Outcome scores are useful tools with respect to quantifying how pain and limitations in strength and movement affect the patient’s functionality and lifestyle. Three shoulder outcome methods [Oxford, Constant and QuickDASH (Disability of the Arm, Shoulder and Hand)] are commonly used in practice but collectively consist of 34 questions, taking approximately 7 min to complete. We have developed a concise shoulder assessment to derive three equivalent outcome scores in a 12-item patient-reporting questionnaire. Methods Outcome scores from 1285 outpatients of an upper limb clinic were collected. The patient cohort consisted of 462 females and 823 males with a mean (SD) age of 47.2 (16.79) years (range 13 years to 90 years). Using a correlation matrix, a 12-item questionnaire was drafted. The combined shoulder assessment was validated by 227 patients; consisting of 101 females and 126 males with a mean (SD) age of 47.91 (16.63) years (range 13 years to 88 years). Results Agreement was achieved between the two methods, with an equivalent Oxford Shoulder Score intraclass correlation (ICC) of 0.930, equivalent Constant Shoulder Score ICC of 0.942 and equivalent QuickDASH ICC of 0.869. Bland–Altman analyses showed no systematic differences. Large effect sizes highlighted the responsiveness to change. Conclusions The new combined shoulder assessment is a more convenient and patient-friendly method to obtain equivalent Oxford, Constant and QuickDASH shoulder outcome scores.
DNM3, p65 and p53 from exosomes represent potential clinical diagnosis markers for glioblastoma multiforme
Authors: Yang Jian-kai , Song Jian , Huo Hao-ran , Zhao Yin-long , Zhang Guang-yu , Zhao Zong-mao , Sun Guo-zhu , Jiao Bao-hua 
Published: November 2017

Background: Glioblastoma multiforme (GBM) is the most aggressive and deadly primary brain cancer that arises from astrocytes and classified as grade IV. Recently, exosomes have been reported as an essential mediator in diverse cancer carcinogenesis and metastasis. However, their role in GBM is still unclear. In this study, we aimed to investigate whether blood exosomes can be potential clinical diagnostic markers for GBM. Methods: We used a xenograft orthotopic mouse model to detect the differentially expressed genes in the brain and blood exosomes of original/recurrent GBM. Results: We found that recurrent GBM had stronger growth capacity and lethality than original GBM in the mouse model. A gene microarray of original tumors and blood exosomes from GBM orthotopic xenografts results showed that DNM3, p65 and CD117 expressions increased, whereas PTEN and p53 expressions decreased in both original tumors and blood exosomes. In the recurrent GBM tumor model, DNM3 and p65 showed increased expressions, whereas ST14 and p53 showed decreased expressions in tumor and blood exosomes of the recurrent GBM mouse model. Conclusion: In summary, we found that DNM3, p65 and p53 had a similar trend in brain and blood exosomes both for original and recurrent GBM, and could serve as potential clinical diagnostic markers for GBM.
Epidemiology and Impact on Performance of Lower Extremity Stress Injuries in Professional Basketball Players
Authors: Khan Moin , Madden Kim , Burrus M. Tyrrell , Rogowski Joseph P. , Stotts Jeff , Samani Marisa J. , Sikka Robby , Bedi Asheesh 
Published: November 2017

Background: Professional basketball players in the National Basketball Association (NBA) subject their lower extremities to significant repetitive loading during both regular-season and off-season training. Little is known about the incidence of lower extremity bony stress injuries and their impact on return to play and performance in these athletes. Hypothesis: Stress injuries of the lower extremity will have significant impact on performance. Study Design: Case series. Level of Evidence: Level 4. Methods: All bony stress injuries from 2005 to 2015 were identified from the NBA. Number of games missed due to injury and performance statistics were collected from 2 years prior to injury to 2 years after the injury. A linear regression analysis was performed to determine the impact of injury for players who returned to sport. Results: A total of 76 lower extremity bony stress injuries involving 75 NBA players (mean age, 25.4 ± 4.1 years) were identified. Fifty-five percent (42/76) involved the foot, and most injuries occurred during the regular season (82.9%, 63/76), with half occurring within the first 6 weeks. Among players who sustained a fifth metatarsal stress fracture, 42.9% were unable to return to professional play. Players who sustained stress injuries had reduced play performance, specifically related to number of games played ( P = 0.014) and number of steals per game ( P = 0.004). Players who had surgery had significantly better performance at 2 years than those who were managed nonoperatively, independent of the type of injury (β = 4.561; 95% CI, 1.255-7.868). Conclusion: Lower extremity bony stress injuries may significantly affect both short- and long-term player performance and career length. Stress injuries result in decreased player performance, and surgical intervention results in improved performance metrics compared with those treated using conservative methods. Clinical Relevance: Stress injuries result in decreased player performance, and surgical intervention results in improved performance metrics.
Noninvasive Liver Assessment in Adult Patients With Fontan Circulation Using Acoustic Radiation Force Impulse Elastography and Hepatic Magnetic Resonance Imaging
Authors: Buendía-Fuentes F. , Melero-Ferrer J. L. , Plaza-López D. , Rueda-Soriano J. , Osa-Saez A. , Aguero J. , Calvillo-Batllés P. , Fonfria-Esparcia C. , Ballesta-Cuñat A. , Martí-Bonmatí L. , Martínez-Dolz L. 
Published: November 2017

Background: Patients who have undergone the Fontan procedure are at risk of developing hepatic dysfunction. However, broad recommendations regarding liver monitoring are limited. The purpose of this study was to characterize the frequency of liver disease in adult Fontan patients using multimodality imaging (hepatic magnetic resonance imaging [MRI], acoustic radiation force impulse [ARFI] elastography, or hepatic ultrasound). Methods: In a prospective cross-sectional analysis of adult patients palliated with a Fontan procedure, hepatic MRI, ARFI, and hepatic ultrasound were used to assess for liver disease. The protocol compared (1) varying prevalence of liver disease based on each imaging technique, (2) agreement between different techniques, and (3) association between noninvasive imaging diagnosis of liver disease and clinical variables, including specific liver disease biomarkers. Results: Thirty-seven patients were enrolled. The ARFI results showed high wave propagation velocity in 35 patients (94.6%). All patients had some abnormality in the hepatic MRI. Specifically, 8 patients (21.6%) showed signs of chronic liver disease, 10 patients (27%) had significant liver fibrosis, and 27 patients (73%) had congestion. No correlation was found between liver stiffness measured as propagation velocity and hepatic MRI findings. Only 7 patients had an abnormal hepatic ultrasound study. Conclusions: There is an inherent liver injury in adult Fontan patients. Signs of liver disease were observed in most patients by both hepatic MRI and ARFI elastography but not by ultrasound imaging. Increased liver stiffness did not identify specific disease patterns from MRI, supporting the need for multimodality imaging to characterize liver disease in Fontan patients.
Hepatocyte nuclear factor 1A deficiency causes hemolytic anemia in mice by altering erythrocyte sphingolipid homeostasis
Authors: von Wnuck Lipinski Karin , Weske Sarah , Keul Petra , Peters Susann , Baba Hideo A. , Heusch Gerd , Gräler Markus H. , Levkau Bodo 
Published: November 2017

Key Points
HNF1A deficiency in mice leads to non–cell-autonomous anemia caused by altered red blood cell (RBC) sphingolipids leading to hemolysis. Sphingosine loading of WT RBCs phenocopies osmotic fragility and high calcium of HNF1A−/− RBCs due to suppressed plasma-membrane Ca2+-ATPase.
High Circulating Free Thyroxine Levels May Increase the Risk of Frailty: The Rotterdam Study
Authors: Bano Arjola , Chaker Layal , Schoufour Josje , Ikram M Arfan , Kavousi Maryam , Franco Oscar H , Peeters Robin P , Mattace-Raso Francesco U S 
Published: November 2017

Abstract

Context
Thyroid hormones affect metabolism in various tissues, organs, and systems. However, the overall impact of thyroid function on an individual’s vulnerability to adverse outcomes remains unclear.

Objective
To investigate the cross-sectional and prospective association of thyroid function with the frailty index, a well-established measure of overall health.

Design and Setting
The Rotterdam Study, a population-based, prospective cohort study.

Participants and Main Outcome Measurements
Participants with baseline measurements of thyroid function and the frailty index were eligible. The frailty index was measured at baseline and after a median follow-up time of 10.1 years (interquartile range, 5.7 to 10.8 years). A higher frailty index indicated a worse health state. We assessed the association of thyroid function with frailty at baseline, frailty at follow-up, and frailty changes over time, adjusting for age, sex, cohort, smoking, alcohol, and education.

Results
We included 9640 participants (mean age, 64.9 years). There was a U-shaped association of thyrotropin (TSH; P &lt; 0.0003) and free thyroxine (FT4; P &lt; 0.0001) with frailty at baseline. There was no association of TSH, but a positive association of FT4 with frailty at follow-up and frailty changes over time (β, 1.22; confidence interval, 0.73 to 1.72 per 1 unit FT4).

Conclusion
In this population-based study, participants with low and high thyroid function were more likely to be frail than participants with normal thyroid function. However, only those with higher FT4 levels had an increased risk of becoming more frail over time. The identification of FT4 as a potential marker of health deterioration could have future implications regarding the prediction and prevention of frailty.
Lysyl oxidases regulate fibrillar collagen remodelling in idiopathic pulmonary fibrosis
Authors: Tjin Gavin , White Eric S. , Faiz Alen , Sicard Delphine , Tschumperlin Daniel J. , Mahar Annabelle , Kable Eleanor P. W. , Burgess Janette K. 
Published: November 2017

ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with few effective therapeutic options. Structural remodelling of the extracellular matrix [i.e. collagen cross-linking mediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4)] might contribute to disease pathogenesis and represent a therapeutic target. This study aimed to further our understanding of the mechanisms by which LO inhibitors might improve lung fibrosis. Lung tissues from IPF and non-IPF subjects were examined for collagen structure (second harmonic generation imaging) and LO gene (microarray analysis) and protein (immunohistochemistry and western blotting) levels. Functional effects (collagen structure and tissue stiffness using atomic force microscopy) of LO inhibitors on collagen remodelling were examined in two models, collagen hydrogels and decellularized human lung matrices. LOXL1/LOXL2 gene expression and protein levels were increased in IPF versus non-IPF. Increased collagen fibril thickness in IPF versus non-IPF lung tissues correlated with increased LOXL1/LOXL2, and decreased LOX, protein expression. β-Aminoproprionitrile (β-APN; pan-LO inhibitor) but not Compound A (LOXL2-specific inhibitor) interfered with transforming growth factor-β-induced collagen remodelling in both models. The β-APN treatment group was tested further, and β-APN was found to interfere with stiffening in the decellularized matrix model. LOXL1 activity might drive collagen remodelling in IPF lungs. The interrelationship between collagen structural remodelling and LOs is disrupted in IPF lungs. Inhibition of LO activity alleviates fibrosis by limiting fibrillar collagen cross-linking, thereby potentially impeding the formation of a pathological microenvironment in IPF.
Comprehensive analysis of gene expression patterns in Friedreich's ataxia fibroblasts by RNA sequencing reveals altered levels of protein synthesis factors and solute carriers
Authors: Napierala Jill Sergesketter , Li Yanjie , Lu Yue , Lin Kevin , Hauser Lauren A. , Lynch David R. , Napierala Marek 
Published: November 2017

ABSTRACT
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease usually caused by large homozygous expansions of GAA repeat sequences in intron 1 of the frataxin (FXN) gene. FRDA patients homozygous for GAA expansions have low FXN mRNA and protein levels when compared with heterozygous carriers or healthy controls. Frataxin is a mitochondrial protein involved in iron–sulfur cluster synthesis, and many FRDA phenotypes result from deficiencies in cellular metabolism due to lowered expression of FXN. Presently, there is no effective treatment for FRDA, and biomarkers to measure therapeutic trial outcomes and/or to gauge disease progression are lacking. Peripheral tissues, including blood cells, buccal cells and skin fibroblasts, can readily be isolated from FRDA patients and used to define molecular hallmarks of disease pathogenesis. For instance, FXN mRNA and protein levels as well as FXN GAA-repeat tract lengths are routinely determined using all of these cell types. However, because these tissues are not directly involved in disease pathogenesis, their relevance as models of the molecular aspects of the disease is yet to be decided. Herein, we conducted unbiased RNA sequencing to profile the transcriptomes of fibroblast cell lines derived from 18 FRDA patients and 17 unaffected control individuals. Bioinformatic analyses revealed significantly upregulated expression of genes encoding plasma membrane solute carrier proteins in FRDA fibroblasts. Conversely, the expression of genes encoding accessory factors and enzymes involved in cytoplasmic and mitochondrial protein synthesis was consistently decreased in FRDA fibroblasts. Finally, comparison of genes differentially expressed in FRDA fibroblasts to three previously published gene expression signatures defined for FRDA blood cells showed substantial overlap between the independent datasets, including correspondingly deficient expression of antioxidant defense genes. Together, these results indicate that gene expression profiling of cells derived from peripheral tissues can, in fact, consistently reveal novel molecular pathways of the disease. When performed on statistically meaningful sample group sizes, unbiased global profiling analyses utilizing peripheral tissues are critical for the discovery and validation of FRDA disease biomarkers.
A superhydrophobic cone to facilitate the xenomonitoring of filarial parasites, malaria, and trypanosomes using mosquito excreta/feces
Authors: Cook Darren A.N. , Pilotte Nils , Minetti Corrado , Williams Steven A. , Reimer Lisa J. 
Published: November 2017

Background: Molecular xenomonitoring (MX), the testing of insect vectors for the presence of human pathogens, has the potential to provide a non-invasive and cost-effective method for monitoring the prevalence of disease within a community. Current MX methods require the capture and processing of large numbers of mosquitoes, particularly in areas of low endemicity, increasing the time, cost and labour required. Screening the excreta/feces (E/F) released from mosquitoes, rather than whole carcasses, improves the throughput by removing the need to discriminate vector species since non-vectors release ingested pathogens in E/F. It also enables larger numbers of mosquitoes to be processed per pool. However, this new screening approach requires a method of efficiently collecting E/F. Methods: We developed a cone with a superhydrophobic surface to allow for the efficient collection of E/F. Using mosquitoes exposed to either Plasmodium falciparum, Brugia malayi or Trypanosoma brucei brucei, we tested the performance of the superhydrophobic cone alongside two other collection methods. Results: All collection methods enabled the detection of DNA from the three parasites. Using the superhydrophobic cone to deposit E/F into a small tube provided the highest number of positive samples (16 out of 18) and facilitated detection of parasite DNA in E/F from individual mosquitoes. Further tests showed that following a simple washing step, the cone can be reused multiple times, further improving its cost-effectiveness. Conclusions: Incorporating the superhydrophobic cone into mosquito traps or holding containers could provide a simple and efficient method for collecting E/F. Where this is not possible, swabbing the container or using the washing method facilitates the detection of the three parasites used in this study.