bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteasome Inhibitors Reduce Thrombospondin-1 Release in Human Dysferlin-Deficient Myotubes
Authors: Fernández-Simón Esther , Lleixà Cinta , Suarez-Calvet Xavier , Diaz-Manera Jordi , Illa Isabel , Gallardo Eduard , de Luna Noemí 
Published: December 2019

Abstract
Background: Dysferlin is a type-II transmembrane protein and the causative gene of dysferlinopathies, which are characterized by absence or marked reduction in dysferlin protein and muscle weakness. Dysferlin is implicated in vesicle fusion, trafficking, and membrane repair. The muscle biopsy of patients with dysferlinopathy is characterized by the presence of inflammatory infiltrates. Release of thrombospondin-1 (TSP-1) by dysferlin deficient muscle has been reported as a possible factor of the inflammation observed in the muscle of both human and mouse models of dysferlinopathy. It has also been reported that treatment with vitamin D3 enhances dysferlin expression. The ubiquitin-proteasome system recognizes and removes proteins that fail to fold or assemble properly and previous studies suggest that its inhibition could have a therapeutic implication in muscle dystrophies. Here we assessed whether inhibition of the ubiquitin proteasome system prevented degradation of dysferlin in immortalized myoblasts from a patient carrying two missense mutationsMethods: Dysferlin deficient myotubes were treated with EB1089, a vitamin D3 analog, oprozomib and ixazomib to assess proteasome inhibition. Western blot was performed to analyze the effect of the different treatments on the recovery of dysferlin and myogenin expression. TSP-1 was quantified using Enzyme Linked Immunosorbent Assay to analyze the effect of these drugs on its release.A membrane repair assay was designed to assess the ability of treated myotubes to recover after membrane injury. Data were analyzed using a one-way ANOVA test followed by by Tukey post hoc test and analysis of variance. Ap≤0.05 was considered statistically significant. Results : Treatment with proteasome inhibitors and EB1089 resulted in a slight increase of dysferlin expression which was accompanied by a low increase of myogenin expression. Also, EB1089 and proteasome inhibitors reduced the release of TSP-1 in myotubes from a dysferlinopathy patient. However, the increase of dysferlin had no effect on the repair of muscle membrane after injury. Conclusions: Our findings indicate that the ubiquitin-proteasome system might not be the main mechanism of mutant dysferlin degradation. However, its inhibition could help to improve muscle inflammation by reducing TSP-1 release.
Noise after total knee arthroplasty has limited effect on joint awareness and patient reported clinical outcomes
Authors: Taniguchi Hiroto , Itoh Masafumi , Yoshimoto Nobuyuki , Itou Junya , Kuwashima Umito , Okazaki Ken 
Published: December 2019

Abstract
BackgroundSome patients complain of noise after total knee arthroplasty (TKA). Controversy still exists how the noise affect the clinical outcomes including joint awareness after TKA. Forgotten Joint Score-12 (FJS-12) measures the clinical outcomes focusing on joint awareness after surgery. The Knee Society Scoring System-2011 (KSS-2011) includes questionnaires for satisfaction, expectation, and functional activities. The aim of this study is to clarify the relationship among FJS-12, KSS-2011 and the noise. Furthermore, the relationship between FJS-12 and KSS-2011 was validated. MethodsUsing the FJS-12 and KSS-2011, 295 knees from 225 patients who underwent TKA was retrospectively evaluated. Noise perception was evaluated by a questionnaire with five grades which is a method that follows the questionnaire form of FJS-12 [“Are you aware of the noise of your artificial joint?” ; never, almost never, seldom, sometimes, mostly]. The correlations among FJS-12, KSS-2011, and noise were analyzed. In addition, patients were divided into four groups based on the mechanism of their implant [cruciate retaining, posterior stabilized, cruciate sacrificed, and bicruciate stabilized (BCS)]. FJS-12, KSS-2011, and noise were compared among the groups. ResultsA strong correlation was observed between FJS-12 and the total score of KSS-2011 (0.70; P < 0.001). FJS-12 also was correlated with KSS-2011 subcategories for “symptoms,” “satisfaction,” and “standard activities” that these correlation coefficients were approximately 0.60. Noise was limited to have weak correlations with FJS-12 (0.28; P < 0.001) and KSS-2011 (0.20 P < 0.001). With comparison among the TKA mechanisms, BCS showed significantly better KSS-2011 and greater range of movement but worse noise scores.ConclusionsNoise perception after TKA had limited effect on joint awareness and clinical outcomes. FJS-12 was correlated strongly with KSS-2011 and associated with satisfaction, residual symptoms, and daily activities as assessed by KSS-2011 subscores.
Comparisons among three approaches—two minimally invasive and one conventional—for total knee arthroplasty: a retrospective cohort study with minimum follow-up of 10 years
Authors: Yuan Fuzhen , Sun Zewen , Fan Baoshi , Jiang Dong , Zhang Jiying , Yu Jiakuo 
Published: December 2019

Abstract
BackgroundFew studies have investigated whether the mini-medial parapatellar (MMP) and quadriceps-sparing (QS) approaches have good long-term results compared to the conventional medial parapatellar (MP) approach in terms of clinical evaluations and radiographic assessments for total knee arthroplasty (TKA). The purpose of this study was to perform comparisons among the MMP, QS and MP approaches with a follow-up at 10 to 17 years.MethodsThis is a retrospective comparative study of 93 patients who underwent MMP TKA (32 TKAs), QS TKA (47 TKAs) or MP TKA (31 TKAs) with the same arthroplasty system. The clinical evaluations were performed according to the new American Knee Society score (KSS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the visual analogue scale (VAS), range of motion (ROM), incidence of anterior knee pain (AKP), the Feller patellofemoral score (PFS), the reoperation rate and the complication rates. Radiographic assessments included observation of the mechanical axis of the lower limb and calculations of the lateral distal femoral angle (LDFA), femoral flexion angle (FFA), medial proximal tibial angle (MPTA), tibial slope angle (TSA), lateral patella displacement (LPD), and lateral patella tilt (LPT).ResultsThere were no differences in the long-term follow-up results of the new KSS, WOMAC score, ROM, VAS, patellofemoral functions, reoperation rate or complication rates among the groups. In addition, no radiographic differences in terms of lower limb mechanical axis or femoral, tibial or patellar position were observed.ConclusionThese results provide conclusive evidence that equivalent, long-term clinical results can be obtained using any one of these three approaches.
Coexisting sonographic features of “tumor neovascularization-like pattern” and “echogenic areas” in thyroid nodules: Diagnostic performance in prediction of papillary carcinoma
Authors: Tong Mengying , Qiu Meng , Li Shuang , Feng Xiao , Guo Liying , Xie Wenlong , Jia Juanjuan , Che Ying 
Published: December 2019

Abstract
Purpose To determine the diagnostic performance of the sonographic finding of tumor neovascularization-like patterns and echogenic areas in differentiating papillary carcinomas from benign nodules.Materials and methods We prospectively analyzed ultrasound-guided fine-needle aspiration (FNA) of thyroid nodules for the two features. In total, 299 nodules (evenly distributed benign vs papillary carcinoma) were evaluated by two blinded readers for intense small penetrating vessels and homogenous mild hyper-echoic areas within the nodules and correlated with FNA-confirmed pathologic diagnosis. A set of nodules with and without the features was selected for further pathologic review and comparison to establish a pathologic basis for the finding.Results The specificity of the “tumor neovascularization-like pattern” and “echogenic areas” in papillary thyroid cancers (PTCs) was 90.6% and 91.3%, respectively. There was a significant correlation, with P < 0.0001, between the “tumor neovascularization-like pattern” and “echogenic areas” in PTCs on both sonographic and pathologic levels. Additionally, the newly identified features as a single variable were more predictive of malignancy than the well-studied features. Inclusion of these new features markedly improved the predictive ability of PTC (AUROC = 0.873 versus 0.801, P < 0.0001).Conclusion Despite their relatively low sensitivity, the “tumor neovascularization-like pattern” and “echogenic areas” are highly specific for PTC and can be a useful sonographic finding in decisions regarding FNA.
The DLC-1 tumor suppressor is involved in regulating immunomodulation of human mesenchymal stem cells through interacting with the Notch1 protein
Authors: Na Tao , Zhang Kehua , Yuan Bao-Zhu 
Published: December 2019

Abstract
Immunomodulatory activities of human mesenchymal stem cells (hMSCs) have been widely accepted as the most critical function of the cells for exerting its therapeutic effects. The activities include the inhibition by hMSCs on pro-inflammatory CD4 + -T lymphocytes, and the release of immunomodulatory molecules, like IDO1. However, the detailed mechanisms responsible for regulating the immunomodulation of hMSCs still remain largely unknown. Previously, the Notch1 protein has been demonstrated to be able to promote the immunomodulation of hMSCs through inhibiting CD4 + -Th1 lymphocyte proliferation and enhancing IDO1 expression. The present study further revealed that it was the Notch1-Hey1 axis, rather than the Notch1-Hes1 axis, that was likely responsible for mediating the immunomodulation of the Notch1 signaling. Meanwhile, following a previously proposed hypothesis to identify proteasome-regulated protein(s) for limiting the activity of the Notch1 signaling in hMSCS, the DLC-1 tumor suppressor was identified to be such a candidate protein, which was subjected to protein degradation mediated by the DDB1 and FBXW5 E3 ligases . It was further shown that the DLC-1 signaling composing of DLC-1, Rock1 and FBXW5 proteins was involved in inhibiting the immunomodulation of hMSCs. More importantly, the immunomodulation was achieved through an interaction between the DLC-1-FBXW5-Rock1 signaling and the Notch1-Hey1 signaling . In fact, the present study a novel function of DLC-1 tumor suppressor as well as proposed a new mutual exclusion mechanism likely responsible for fine-tuning the immunomodulation of hMSCs.
LRIG1 gene copy number analysis by ddPCR and correlations to clinical factors in breast cancer
Authors: Faraz Mahmood , Tellström Andreas , Ardnor Christina Edwinsdotter , Grankvist Kjell , Huminiecki Lukasz , Tavelin Björn , Henriksson Roger , Hedman Håkan , Ljuslinder Ingrid 
Published: December 2019

Abstract
Background Leucine-rich repeats and immunoglobulin-like domains 1 ( LRIG1 ) copy number alterations and unbalanced gene recombination events have been reported to occur in breast cancer. Importantly, LRIG1 loss was recently shown to predict early and late relapse in stage I-II breast cancer.Methods We developed droplet digital PCR (ddPCR) assays for the determination of relative LRIG1 copy numbers and used these assays to analyze LRIG1 in twelve healthy individuals, 34 breast tumor samples previously analyzed by fluorescence in situ hybridization (FISH), and 423 breast tumor cytosols.Results Four of the LRIG1 /reference gene assays were found to be precise and robust, showing copy number ratios close to 1 (mean, 0.984; standard deviation, +/-0.031) among the healthy control population. The correlation between the ddPCR assays and previous FISH results was low, possibly because of the different normalization strategies used. One in 34 breast tumors (2.9%) showed an unbalanced LRIG1 recombination event. LRIG1 copy number ratios were associated with the breast cancer subtype, steroid receptor status, ERBB2 status, tumor grade, and nodal status. Both LRIG1 loss and gain were associated with unfavorable metastasis-free survival; however, they did not remain significant prognostic factors after adjustment for common risk factors in the Cox regression analysis. Furthermore, LRIG1 loss was not significantly associated with survival in stage I and II cases.Conclusions Although LRIG1 gene aberrations may be important determinants of breast cancer biology, and prognostic markers, the results of this study do not verify an important role for LRIG1 copy number analyses in predicting the risk of relapse in early-stage breast cancer.
Barriers and facilitators of community based health insurance membership in rural Amhara region, northwest Ethiopia: A qualitative study
Authors: Demissie Getu Debalkie , Atnafu Asmamaw 
Published: December 2019

Abstract
Background: More than 150 million people encounter huge cost of health expenses every year, and most of these treatment seekers face poverty owing to out of pocket payments. Community-based health insurance won popularity as a makeshift health financing mechanism for out of pocket payments in poor communities. The aim of this study was to identify the facilitators and impediments of enrollment to community based health insurance in rural parts of the Amhara region, Ethiopia.Method: Focus group discussions (FGD) were the main research methodology supplemented by key informant interviews (KII). The FGD participants were selected by purposive sampling techniques based on the membership status of CBHI (members or non-members). Six FGDs and four key informant interviewees were conducted in March 2018 in three districts. Before analyzing the data, all FGDs and KIIs were transcribed and transferred into Atlasti version 7.1 software. Thematic analysis was done according to key themes arising from the data. Results: Low level of awareness, perception of high amount of premium, poor perception of quality of services and lack of trust in community based health insurance are the barriers to membership in community based health insurance.Conclusion: There has been a low level of awareness and misconception about community based health insurance. The major reason for not joining CBHI was incapacity to pay the premium.
Is Leishmaniasis adequately notified in Sri Lanka? A survey among doctors from high endemic district of Sri Lanka.
Authors: Hewawasam Chandana , Weerakoon Hema S , Thilakan Vyshnavi , Lelwala Tishni , Prasanka Kalana , Rathnayaka Amila S , Gamage Shanika , Agampodi Suneth 
Published: December 2019

Abstract
Background : Leishmaniasis is a notifiable disease in Sri Lanka since 2008. Previous studies show a gap in the notification. Purpose of the present study was to determine the Knowledge, attitudes and practice of medical officers regarding leishmaniasis. Methods : A cross-sectional study was conducted in Anuradhapura district which reported the highest prevalence of leishmaniasis. Participants from public and private health care institutes in the area filled a self-administered questionnaire in the presence of the investigators. Results : One hundred and eighty-eight (188) medical officers (involved in treating 75,326 population) completed the questionnaire. Of them, 95.7% (n=177) were aware of leishmaniasis as a parasitic infection and 84.7% (n=155) correctly identified Leishmania donovani as the causative organism in Sri Lanka. From the respondents, 96.8% (n=181) knew that the vector of leishmaniasis is sandfly. Cutaneous leishmaniasis was reported as the most prevalent form of leishmaniasis in the country by 94.1% (n=176). Nearly half of the population (54.1%, n=98) was aware of the fact that Anuradhapura district has the highest prevalence of the disease. Many of them had the idea that leishmaniasis is an emerging disease (84.3%, n=155) and early diagnosis is important in controlling the disease (89.1%, n=163). Although about three fourth (73.7 %, n=123) of the population mentioned that leishmaniasis should be notified at first clinical suspicion, only 42.5% (n=74) were aware that it is a legal requirement. Some medical officers (22%, n=39) believed the current notification system in the country is not effective. Unavailability of notification forms (36.8%, n=60), heavy workload (50.3%, n=85) and inadequate supportive staff (35.1%, n=55) were reported as barriers for timely notification. Even though 58.0% (n=105) of medical officers had suspected leishmaniasis during last eight years period only 19.4% (n=35) had notified. Conclusions : Even though more than 90% of the participants had good theoretical knowledge about leishmaniasis; notification of leishmaniasis is considerably inadequate. This study emphasizes the need for greater efforts to improve the notification of leishmaniasis in Sri Lanka. Keywords : Leishmaniasis, Notification, Physicians, Knowledge, attitude, practice, Sri Lanka
Effectiveness and Feasibility of Using Local Medical University for Capacity Building to Improve Immunization Program in Ethiopia. Implementation Science Study
Authors: Amare Ashenafi T. , Toni Alemayehu T. , Mekonnen Zeleke A. , Endehabtu Berhanu F. , Tilahun Binyam C. 
Published: December 2019

Abstract
Background: Supportive supervision is one of five essential components of the WHO’s Reaching Every District strategy, an operational approach to reach 90%, immunization coverage. However, it is not mostly practiced based on the standard schedule because of capacity and low number of staffs in the health system. When it is practiced after long interval, it focuses more on inspection and finding lacunas. Taking into account the 54 universities in Ethiopia, the fundamental idea in this implementation science research is to test the feasibility and effectiveness of a Capacity Building and Mentorship Program in Immunization (CBMPI) by medical and health science colleges aimed at supplementing the current approach. Methods: This study applied a pre-post quasi experimental research design. The study included health workers of 30 health facilities (15 intervention and 15 control) followed for six months. To assess effectiveness on immunization coverage and a change in reaching every district strategy implementation difference in difference analysis was used to estimate the effect of the intervention implementation over time. Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework was used to evaluate the implementation process. Results: The findings of the study indicated that the intervention package has a statistically significant effect (P=0.0001) in the overall implementation of Reaching Every District (RED) outcomes. The difference in difference analysis also indicated that health facilities in the intervention district have shown a higher Penta III coverage (17.4%) and complete vaccination coverage (16.6%) that is attributable to the intervention package. Similarly, knowledge and skills of health workers improved significantly (P<0.05) after the intervention in most of the performance measures. During the qualitative evaluation, the key informants mentioned that the CBMPI program was effective and the new approach was acceptable by health workers for integration in the routine EPI program. Conclusions: In conclusion, capacity building and mentorship by well-trained personnel with the appropriate knowledge and skills have positive effects on immunization program indicators. Thus, it is recommended to do implementation study within the framework of national immunization program to facilitate policy adoption and readiness for routine use in large scale. This work was supported by the Bill & Melinda Gates Foundation, Grant Number OPP1191298
Investigation and invention in carbapenem-resistant Klebsiella pneumoniae infection cases associated with Endoscopic retrograde cholangiopancreatography operation
Authors: Yuan Yuhua , Shi Qiucheng , Fang Li , Zhao Jin , Ni Yaqin , Tu Fangjuan , Wu Zhenbo , Zhu Feiteng , Chen Dongrong , Chen Yan , Yu Yunsong 
Published: December 2019

Abstract
Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is associated with nosocomial infections that poses a serious threat to public health. According to a previous study, endoscopic retrograde cholangiopancreatography (ERCP) is considered a risk factor of CRKP transmission in the hospital. Methods: In this study, two cases infected with CRKP after ERCP were investigated. The origin of CRKP was determined by collecting the isolates from patients and screening the environment for ERCP units and the specific endoscopes. The antimicrobials susceptibility testing and molecular typing were performed for these CRKP. After post-ERCP infection happened, the procedure of endoscope disinfection was changed and hydrogen dioxide disinfection of ERCP unit was performed.Results: A total of five CRKP isolates were obtained from patients and screening the environment for ERCP units and the specific endoscopes, including three from the patients and two from the ERCP operating room. The CRKP from the patients and environment were both ST11, and the pulsed-field gel electrophoresis results showed that they shared identical bands, which indicated that the contaminated environment was associated with the nosocomial CRKP infections. After the control measures of endoscopes and hydrogen dioxide disinfection, post-ERCP infection decreased in the next six months.Conclusion: Early warning and response system should be established to control the spreading of CRKP in ERCP operation unit.
EFEKTIVITAS PENGGUNAAN LINGKUNGAN SEBAGAI SUMBER BELAJAR MATERI IPA POKOK BAHASAN EKOSISTEM PADA KELAS VII SMP N 2 PRINGAPUS KABUPATEN SEMARANG TERHADAP HASIL BELAJAR SISWA
Authors: Jannah Miftakhul 
Published: December 2019

Pemanfaatan lingkungan sebagai sumber belajar diartikan suatu tem- pat mengajar yang menghadapkan peserta didik dengan benda-benda dan peristiwa-peristiwa yang sebenarnya. Dengan demikian peserta didik dapat belajar secara nyata, tidak merasa bosan, mudah dimengerti dan diingat, serta pengkajian yang efektif dan lebih cepat, karena pemanfaatan lingkungan sebagai sumber belajar kontekstual mempunyai unsur-unsur yang membuatnya lebih baik dengan pembelajaran yang bersifat konven- sional, diantaranya ceramah.Penelitian ini bertujuan untuk mengetahui efektivitas pembelajaran IPA khususnya kelas VII menggunakan lingkungan langsung sebagai sumber belajar terhadap hasil belajar siswa kelas VII SMP N 2 Pringapus Kabupaten Semarang pada poko bahasan materi ekosistem. Hasil pene- litian ini merupakan penelitian kuantitatif dengan metode penelitian eks- perimen terpola bentuk posttest control design. Populasi dalam penelitian ini adalah peserta didik kelas VII SMP N 2 Pringapus Semarang, yaitu kelas VII A sebagai kelas eksperimen dan kelas VII C sebagai kelas kontrol. Pen- gumpulan data dalam penelitian ini menggunakan metode tes, observasi dan demonstrasi. Data penelitian yang terkumpul digunakan analisis uji t-test.Berdasarkan hasil t-test, dihasilkan bahwa t hitung = 2,947 dan ttabel = 1,68 dengan taraf nyata 5% Karena t hitung ttabel maka data tersebut signifikan. Sedangkan untuk uji hipotesis pihak kanan dibandingkan dengan KKM diperoleh thitung = 9,2876 dan ttabel = 1,714 maka penggunaan lingkun- gan sebagai sumber belajar dapat mencapai KKM yang telah ditentukan yaitu 70. Dengan demikian pembelajaran IPA menggunakan lingkungan sebagai sumber belajar efektif terhadap hasil belajar siswa Kelas VII SMP N 2 Pringapus Kabupaten Semarang pada mata pelajaran IPA pokok bahasan.