bluuebunny/crossref_metadata_2025_split huggingface dataset:
A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease
Authors: Hong Young Bin , Lee Ja Hyun , Park Jin-Mo , Choi Yu-Ri , Hyun Young Se , Yoon Bo Ram , Yoo Jeong Hyun , Koo Heasoo , Jung Sung-Chul , Chung Ki Wha , Choi Byung-Ok 
Published: December 2013

Abstract

Background
Charcot-Marie-Tooth disease (CMT) is a heterogeneous disorder of the peripheral nervous system. So far, mutations in hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit (HADHB) gene exhibit three distinctive phenotypes: severe neonatal presentation with cardiomyopathy, hepatic form with recurrent hypoketotic hypoglycemia, and later-onset axonal sensory neuropathy with episodic myoglobinuria.

Methods
To identify the causative and characterize clinical features of a Korean family with motor and sensory neuropathies, whole exome study (WES), histopathologic study of distal sural nerve, and lower limb MRIs were performed.

Results
WES revealed that a compound heterozygous mutation in HADHB is the causative of the present patients. The patients exhibited an early-onset axonal sensorimotor neuropathy without episodic myoglobinuria, and showed typical clinical and electrophysiological features of CMT including predominant distal muscle weakness and atrophy. Histopathologic findings of sural nerve were compatible with an axonal CMT neuropathy. Furthermore, they didn’t exhibit any other symptoms of the previously reported HADHB patients.

Conclusions
These data implicate that mutation in HADHB gene can also cause early-onset axonal CMT instead of typical manifestations in mitochondrial trifunctional protein (MTP) deficiency. Therefore, this study is the first report of a new subtype of autosomal recessive axonal CMT by a compound heterozygous mutation in HADHB, and will expand the clinical and genetic spectrum of HADHB.
Clinical and genetic features of Huntington disease in Sri Lanka
Authors: Sumathipala Dulika S , Jayasekara Rohan W , Dissanayake Vajira HW 
Published: December 2013

Abstract

Background
Huntington disease was one of the first neurological hereditary diseases for which genetic testing was made possible as early as 1993. The study describes the clinical and genetic characteristics of patients with Huntington disease in Sri Lanka.

Methods
Data of 35 consecutive patients tested from 2007 to 2012 at the Human Genetics Unit, Faculty of Medicine, University of Colombo was analyzed retrospectively. Clinical data and genetic diagnostic results were reviewed. Statistical analysis was performed using descriptive statistics.

Results
Thirty patients had fully penetrant (FP) CAG repeat mutations and 5 had reduced penetrant (RP) CAG repeat mutations. In the FP group mean ages of onset and diagnosis were 37.5 and 40.4 years, while in the RP group it was 63.0 and 64.8 years respectively. The age of diagnosis ranged from 15 to 72 years, with 2 patients with Juvenile onset (<20 years) and 3 with late onset (>60 years) Huntington disease. The symptoms at diagnosis were predominantly motor (32/35 -91%). Three patients had psychiatric and behavioral disorders. The age difference between onset and genetic diagnosis showed significant delay in females compared to males (p < 0.05). Twenty two (62.8%) had a positive family history, with 13/22 (59.1%) showing a paternal inheritance of the disease. In both groups, those with a family history had a significantly lower age of presentation (p < 0.05). The mean CAG repeat length in patients with FP alleles was 44.6 ± 5 and RP alleles was 37.2 ± 1.1. Age of onset and CAG repeat length of the HTT gene showed significant inverse correlation (p < 0.0005, R2 = 0.727).

Conclusions
The clinical and genetic features seen in patients with Huntington disease in the Sri Lankan study population were similar to that previously reported in literature.
Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of SEC62 gene silencing in human tumor cells
Authors: Linxweiler Maximilian , Schorr Stefan , Schäuble Nico , Jung Martin , Linxweiler Johannes , Langer Frank , Schäfers Hans-Joachim , Cavalié Adolfo , Zimmermann Richard , Greiner Markus 
Published: December 2013

AbstractBackgroundTumor cells benefit from their ability to avoid apoptosis and invade other tissues. The endoplasmic reticulum (ER) membrane protein Sec62 is a key player in these processes. Sec62 is essential for cell migration and protects tumor cells against thapsigargin-induced ER stress, which are both linked to cytosolic Ca2+.SEC62silencing leads to elevated cytosolic Ca2+and increased ER Ca2+leakage after thapsigargin treatment. Sec62 protein levels are significantly increased in different tumors, including prostate, lung and thyroid cancer.MethodsIn lung cancer, the influence of Sec62 protein levels on patient survival was analyzed using the Kaplan-Meier method and log-rank test. To elucidate the underlying pathophysiological functions of Sec62, Ca2+imaging techniques, real-time cell analysis and cell migration assays were performed. The effects of treatment with the calmodulin antagonists, trifluoperazine (TFP) and ophiobolin A, on cellular Ca2+homeostasis, cell growth and cell migration were compared with the effects of siRNA-mediated Sec62 depletion or the expression of a mutatedSEC62variantin vitro. Using Biacore analysis we examined the Ca2+-sensitive interaction of Sec62 with the Sec61 complex.ResultsSec62 overproduction significantly correlated with reduced patient survival. Therefore, Sec62 is not only a predictive marker for this type of tumor, but also an interesting therapeutic target. The present study suggests a regulatory function for Sec62 in the major Ca2+leakage channel in the ER, Sec61, by a direct and Ca2+-sensitive interaction. A Ca2+-binding motif in Sec62 is essential for its molecular function. Treatment of cells with calmodulin antagonists mimicked Sec62 depletion by inhibiting cell migration and rendering the cells sensitive to thapsigargin treatment.ConclusionsTargeting tumors that overproduce Sec62 with calmodulin antagonists in combination with targeted thapsigargin analogues may offer novel personalized therapeutic options.
The influence of the treatment response on the impact of resection margin status after preoperative chemoradiotherapy in locally advanced rectal cancer
Authors: Lee Joo Ho , Chie Eui Kyu , Kim Kyubo , Jeong Seung-Yong , Park Kyu Joo , Park Jae-Gahb , Kang Gyeong Hoon , Han Sae-Won , Oh Do-Youn , Im Seock-Ah , Kim Tae-You , Bang Yung-Jue , Ha Sung W 
Published: December 2013

Abstract

Background
Circumferential resection margin (CRM) and distal resection margin (DRM) have different impact on clinical outcomes after preoperative chemoradiotherapy (CRT) followed by surgery. Effect and adequate length of resection margin as well as impact of treatment response after preoperative CRT was evaluated.

Methods
Total of 403 patients with rectal cancer underwent preoperative CRT followed by total mesorectal excision between January 2004 and December 2010. After applying the criterion of margin less than 0.5 cm for CRM or less than 1 cm for DRM, 151 cases with locally advanced rectal cancer were included as a study cohort. All patients underwent conventionally fractionated radiation with radiation dose over 50 Gy and concurrent chemotherapy with 5-fluorouracil or capecitabine. Postoperative chemotherapy was administered to 142 patients (94.0%). Median follow-up duration was 43.1 months.

Results
The 5-year overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) rates, and locoregional control rates (LRC) were 84.5%, 72.8%, 74.2%, and 86.3%, respectively. CRM of 1.5 mm and DRM of 7 mm were cutting points showing maximal difference in a maximally selected rank method. In univariate analysis, CRM of 1.5 mm was significantly related with worse clinical outcomes, whereas DRM of 7 mm was not. In multivariate analysis, CRM of 1.5 mm, and ypN were prognosticators for all studied endpoints. However, CRM was not a significant prognostic factor for good responders, defined as patients with near total regression or T down-staging, which was found in 16.5% and 40.5% among studied patients, respectively. In contrast, poor responders demonstrated a significant difference according to the CRM status for all studied end-points.

Conclusions
Close CRM, defined as 1.5 mm, was a significant prognosticator, but the impact was only prominent for poor responders in subgroup analysis. Postoperative treatment strategy may be individualized based on this finding. However, findings from this study need to be validated with larger cohort.
Estimating the lifelong health impact and financial burdens of different types of lung cancer
Authors: Yang Szu-Chun , Lai Wu-Wei , Su Wu-Chou , Wu Shang-Yin , Chen Helen HW , Wu Yi-Lin , Hung Mei-Chuan , Wang Jung-Der 
Published: December 2013

AbstractBackgroundOwing to the high mortality and rapidly growing costs related to lung cancer, it is worth examining the health benefits of prevention for major types of lung cancer. This study attempts to quantify the quality-adjusted life expectancy (QALE), loss-of-QALE, and lifetime healthcare expenditures of patients with different pathological types of lung cancer.MethodsA national cohort consisting of 66,535 patients with pathologically verified lung cancer was followed for 13 years (1998–2010) to obtain the survival function, which was further extrapolated to lifetime. Between 2011 and 2012, EuroQol 5-dimension questionnaires were used to measure the quality of life (QoL) for 1,314 consecutive, cross-sectional samples. After multiplying the lifetime survival function by the utility values of QoL, we estimated the QALE and loss-of-QALE. We also collected the monthly healthcare expenditures, which included National Health Insurance-reimbursed and out-of-pocket direct medical costs, for 2,456 patients from 2005 to 2012. These values were multiplied by the corresponding survival probabilities to calculate lifetime healthcare expenditures after adjustments with medical care inflation rates and annual discount rates.ResultsThe QALE for patients with small cell lung cancer, squamous cell carcinoma, and adenocarcinoma were 1.21, 2.37, and 3.03 quality-adjusted life year (QALY), with the corresponding loss-of-QALE of 13.69, 12.22, and 15.03 QALY, respectively. The lifetime healthcare expenditures were US$ 18,455 ± 1,137, 20,599 ± 1,787, and 36,771 ± 1,998, respectively.ConclusionsThe lifelong health impact and financial burdens in Taiwan are heavier for adenocarcinoma than for squamous cell carcinoma. The cost-effectiveness of prevention programs could be directly compared with that of treatment strategies to improve patient value. And the methodology could be applied to other chronic diseases for resources planning of healthcare services.
Awareness of diabetes mellitus among diabetic patients in the Gambia: a strong case for health education and promotion
Authors: Foma Mafomekong Ayuk , Saidu Yauba , Omoleke Semeeh Akinwale , Jafali James 
Published: December 2013

AbstractBackgroundAwareness of various aspects of Diabetes Mellitus (DM) is essential for the prevention, management and control of the disease. However, several studies have consistently shown that awareness of DM in the general population is low. None of these studies, however, was conducted in The Gambia, even though the condition constitutes a major public health problem in the country. In this paper, we assessed the awareness of DM among diabetic patients attending the Medical Out-Patient Department (MOPD) of Royal Victoria Teaching Hospital (RVTH), Banjul.MethodsWe interviewed 200 patients attending the MOPD of RVTH. We used a tool containing questions on patient’s demographic characteristics and awareness of various aspects of DM including general knowledge on DM, causes, complications, management and prevention.ResultsOf the 199 patients who were aware of their condition, only 47% said they knew what DM is. Similarly, 53% of the study participants had no knowledge of the causes of DM and about 50% were not aware of the methods of prevention. 67% knew that DM can result to loss of sight while 46.5% knew that DM can cause poor wound healing. Few respondents knew that DM can lead to kidney failure (13.5%), skin sepsis (12.0%), heart failure (5.5%) and stroke (4.5%). Close to 50% of the respondent did not know how DM can be prevented. Level of education, duration of illness and knowledge of a family member with diabetes were important predictors of knowledge in our study.ConclusionOur study shows that the majority of patients attending the MOPD have poor knowledge on several aspects of DM. Hence, there is need for conscious efforts towards improving the level of awareness through health education and promotion, not limited to the hospital but also within the general population, as part of strategies to prevent, manage and control DM.
Efficacy of low-dose intra-articular tranexamic acid in total knee replacement; a prospective triple-blinded randomized controlled trial
Authors: Sa-ngasoongsong Paphon , Wongsak Siwadol , Chanplakorn Pongsthorn , Woratanarat Patarawan , Wechmongkolgorn Supaporn , Wibulpolprasert Bussanee , Mulpruek Pornchai , Kawinwonggowit Viroj 
Published: December 2013

Abstract

Background
Recently, a number of studies using intra-articular application of tranexamic acid (IA-TXA), with different dosage and techniques, successfully reduced postoperative blood loss in total knee replacement (TKR). However, best of our knowledge, the very low dose of IA-TXA with drain clamping technique in conventional TKR has not been yet studied. This study aimed to evaluate the effectiveness and dose-response effect of two low-dose IA-TXA regimens in conventional TKR on blood loss and blood transfusion reduction.

Methods
Between 2010 and 2011, a triple-blinded randomized controlled study was conducted in 135 patients undergoing conventional TKR. The patients were allocated into three groups according to intra-articular solution received: Control group (physiologic saline), TXA-250 group (TXA 250 mg), and TXA-500 group (TXA 500 mg). The solution was injected after wound closure followed by drain clamping for 2 hours. Blood loss and transfusion were recorded. Duplex ultrasound was performed. Functional outcome and complication were followed for one year.

Results
There were forty-five patients per groups. The mean total hemoglobin loss was 2.9 g/dL in control group compared with 2.2 g/dL in both TXA groups (p > 0.001). Ten patients (22%, control), six patients (13%, TXA-250) and none (TXA-500) required transfusion (p = 0.005). Thromboembolic events were detected in 7 patients (4 controls, 1 TXA-250, and 2 TXA-500). Functional outcome was non-significant difference between groups.

Conclusions
Combined low-dose IA-TXA, as 500 mg, with 2-hour clamp drain is effective for reducing postoperative blood loss and transfusion in conventional TKR without significant difference in postoperative knee function or complication.

Trial registration
ClinicalTrials.gov NCT01850394.
Hospital accreditation, reimbursement and case mix: links and insights for contractual systems
Authors: Ammar Walid , Khalife Jade , El-Jardali Fadi , Romanos Jenny , Harb Hilda , Hamadeh Ghassan , Dimassi Hani 
Published: December 2013

AbstractBackgroundResource consumption is a widely used proxy for severity of illness, and is often measured through a case-mix index (CMI) based on Diagnosis Related Groups (DRGs), which is commonly linked to payment. For countries that do not have DRGs it has been suggested to use CMIs derived from International Classification of Diseases (ICD). Our research objective was to use ICD-derived case-mix to evaluate whether or not the current accreditation-based hospital reimbursement system in Lebanon is appropriate.MethodsOur study population included medical admissions to 122 hospitals contracted with the Lebanese Ministry of Public Health (MoPH) between June 2011 and May 2012. Applying ICD-derived CMI on principal diagnosis cost (CMI-ICDC) using weighing similar to that used in Medicare DRG CMI, analyses were made by hospital accreditation, ownership and size. We examined two measures of 30-day re-admission rate. Further analysis was done to examine correlation between principal diagnosis CMI and surgical procedure cost CMI (CMI-CPTC), and three proxy measures on surgical complexity, case complexity and surgical proportion.ResultsHospitals belonging to the highest accreditation category had a higher CMI than others, but no difference was found in CMI among the three other categories. Private hospitals had a higher CMI than public hospitals, and those more than 100 beds had a higher CMI than smaller hospitals. Re-admissions rates were higher in accreditation category C hospitals than category D hospitals. CMI-ICDC was fairly correlated with CMI-CPTC, and somehow correlated with the proposed proxies.ConclusionsOur results indicate that the current link between accreditation and reimbursement rate is not appropriate, and leads to unfairness and inefficiency in the system. Some proxy measures are correlated with case-mix but are not good substitutes for it. Policy implications of our findings propose the necessity for changing the current reimbursement system by including case mix and outcome indicators in addition to accreditation in hospital contracting. Proxies developed may be used to detect miss-use and provider adverse behavior. Research using ICD-derived case mix is limited and our findings may be useful to inform similar initiatives and other limited-setting countries in the region.
Nb, F-codoped TiO2 hollow spheres with high visible light photocatalytic activity
Authors: Gao Mingqi , Xu Youlong , Bai Yang , Xiao Fang 
Published: December 2013

Abstract
Nb, F-codoped TiO2 hollow spheres (NFTSs) were successfully synthesized via a hydrothermal method with niobium oxide, hydrofluoric acid, and tetrabutyl titanate. The obtained spheres were hollow, with a diameter of about 2 μm, and the sphere wall was made up of nanorods arranged close together. The NFTSs presented anatase phase with more {001} facets exposed, which could be mainly attributed to F ions which were preferentially adsorbed on the {001} facets during the crystal growth process. Ti3+ states in NFTSs were increased due to Nb, F-codoping, resulting in the decrease of the band gap and the red shift of the absorption edge of the NFTSs. The NFTSs exhibited 20.1% higher photocatalytic speed compared to P25 on the degradation of methylene orange.
Atomistic insight into the minimum wear depth of Cu(111) surface
Authors: Li Zengqiang , Huang Yanhua , Zhang Junjie , Yan Yongda , Sun Tao 
Published: December 2013

Abstract
In the present work, we investigate the minimum wear depth of single crystalline Cu(111) under single asperity friction by means of molecular dynamics simulations. The atomistic mechanisms governing the incipient plasticity are elucidated by characterizing specific defect structures and are correlated to the observed mechanical and frictional responses of the material. Furthermore, the effect of probe radius on the friction process is studied. Our simulations indicate that the formation of wear impression is closely associated with defect nucleation and the minimum wear depth is equivalent to the critical penetration depth at which plasticity initiates. It is found that the probe radius has a strong influence on the formation of defect structures and the observed mechanical responses.
A novel pre-processing and adaptive statistical threshold for sphere detection in MIMO systems
Authors: Cao Haiyan , Li Jun , Fang Xin , Wang Xiumin 
Published: December 2013

Abstract
In this paper, an efficient sphere detection (SD) scheme for multiple-input multiple-output (MIMO) systems is presented. The proposed SD scheme can substantially reduce computational complexity by introducing a pre-processing scheme and an adaptive threshold. In particular, our proposed pre-processing scheme is based on an iterative successive interference cancelation (SIC). The proposed adaptive threshold is used to judge whether a traversed path is correct or not and obtained by analyzing the distributions of the correct and erroneous estimates which have the minimum error pattern among all the SD searching paths. Simulation results show that our proposed scheme offers a substantial complexity reduction in terms of the number of visited nodes while keeping a significantly small performance degradation compared to conventional approaches.
Multi-non-binary turbo codes
Authors: Balta Horia , Douillard Catherine , Lucaciu Radu 
Published: December 2013

Abstract
This paper presents a new family of turbo codes called multi-non-binary turbo codes (MNBTCs) that generalizes the concept of turbo codes to multi-non-binary (MNB) parallel concatenated convolutional codes (PCCC). An MNBTC incorporates, as component encoders, recursive and systematic multi-non-binary convolutional encoders. The more compact data structure for these encoders confers some advantages on MNBTCs over other types of turbo codes, such as better asymptotic behavior, better convergence, and reduced latency. This paper presents in detail the structure and operation of an MNBTC: MNB encoding, trellis termination, Max-Log-MAP decoding adapted to the MNB case. It also shows an example of MNBTC whose performance is compared with the state-of-the-art turbo code adopted in the DVB-RCS2 standard.
Designing of interferon-gamma inducing MHC class-II binders
Authors: Dhanda Sandeep Kumar , Vir Pooja , Raghava Gajendra PS 
Published: December 2013

Abstract

Background
The generation of interferon-gamma (IFN-γ) by MHC class II activated CD4+ T helper cells play a substantial contribution in the control of infections such as caused by Mycobacterium tuberculosis. In the past, numerous methods have been developed for predicting MHC class II binders that can activate T-helper cells. Best of author’s knowledge, no method has been developed so far that can predict the type of cytokine will be secreted by these MHC Class II binders or T-helper epitopes. In this study, an attempt has been made to predict the IFN-γ inducing peptides. The main dataset used in this study contains 3705 IFN-γ inducing and 6728 non-IFN-γ inducing MHC class II binders. Another dataset called IFNgOnly contains 4483 IFN-γ inducing epitopes and 2160 epitopes that induce other cytokine except IFN-γ. In addition we have alternate dataset that contains IFN-γ inducing and equal number of random peptides.

Results
It was observed that the peptide length, positional conservation of residues and amino acid composition affects IFN-γ inducing capabilities of these peptides. We identified the motifs in IFN-γ inducing binders/peptides using MERCI software. Our analysis indicates that IFN-γ inducing and non-inducing peptides can be discriminated using above features. We developed models for predicting IFN-γ inducing peptides using various approaches like machine learning technique, motifs-based search, and hybrid approach. Our best model based on the hybrid approach achieved maximum prediction accuracy of 82.10% with MCC of 0.62 on main dataset. We also developed hybrid model on IFNgOnly dataset and achieved maximum accuracy of 81.39% with 0.57 MCC.

Conclusion
Based on this study, we have developed a webserver for predicting i) IFN-γ inducing peptides, ii) virtual screening of peptide libraries and iii) identification of IFN-γ inducing regions in antigen (http://crdd.osdd.net/raghava/ifnepitope/).

Reviewers
This article was reviewed by Prof Kurt Blaser, Prof Laurence Eisenlohr and Dr Manabu Sugai.