bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia
Authors: Al-Khateeb Alyaa , Zahri Mohd K , Mohamed Mohd S , Sasongko Teguh H , Ibrahim Suhairi , Yusof Zurkurnai , Zilfalil Bin A 
Published: March 2011

Abstract

Background
Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.
We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan). The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide substitutions, and by multiplex ligation-dependent probe amplification to detect large rearrangements.

Results
A total of 29 gene sequence variants were reported in 117(76.0%) of the studied subjects. Eight different mutations (1 large rearrangement, 1 short deletion, 5 missense mutations, and 1 splice site mutation), and 21 variants. Eight gene sequence variants were reported for the first time and they were noticed in familial hypercholesterolemic patients, but not in controls (p.Asp100Asp, p.Asp139His, p.Arg471Gly, c.1705+117 T>G, c.1186+41T>A, 1705+112C>G, Dup exon 12 and p.Trp666ProfsX45). The incidence of the p.Arg471Gly variant was 11%. Patients with pathogenic mutations were younger, had significantly higher incidences of cardiovascular disease, xanthomas, and family history of hyperlipidemia, together with significantly higher total cholesterol and low density lipoprotein levels than patients with non-pathogenic variants.

Conclusions
Twenty-nine gene sequence variants occurred among FH patients; those with predicted pathogenicity were associated with higher incidences of cardiovascular diseases, tendon xanthomas, and higher total and low density lipoprotein levels compared to the rest. These results provide preliminary information on the mutation spectrum of this gene among patients with FH in Malaysia.
Resveratrol protects leukemic cells against cytotoxicity induced by proteasome inhibitors via induction of FOXO1 and p27Kip1
Authors: Niu Xiao-Fang , Liu Bao-Qin , Du Zhen-Xian , Gao Yan-Yan , Li Chao , Li Ning , Guan Yifu , Wang Hua-Qin 
Published: March 2011

Abstract

Background
It was reported recently that resveratrol could sensitize a number of cancer cells to the antitumoral effects of some conventional chemotherapy drugs. The current study was designed to investigate whether resveratrol could sensitize leukemic cells to proteasome inhibitors.

Methods
Leukemic cells were treated with MG132 alone or in combination with resveratrol. Cell viability was investigated using MTT assay, and induction of apoptosis and cell cycle distribution was measured using flow cytometry. Western blot and real-time RT-PCR were used to investigate the expression of FOXO1 and p27Kip1. CHIP was performed to investigate the binding of FOXO1 to the p27 Kip1 promoter.

Results
Resveratrol strongly reduced cytotoxic activities of proteasome inhibitors against leukemic cells. MG132 in combination with resveratrol caused cell cycle blockade at G1/S transition via p27Kip1 accumulation. Knockdown of p27Kip1 using siRNA dramatically attenuated the protective effects of resveratrol on cytotoxic actions of proteasome inhibitors against leukemic cells. Resveratrol induced FOXO1 expression at the transcriptional level, while MG132 increased nuclear distribution of FOXO1. MG132 in combination with resveratrol caused synergistic induction of p27Kip1 through increased recruitment of FOXO1 on the p27Kip1 promoter.

Conclusions
Resveratrol may have the potential to negate the cytotoxic effects of proteasome inhibitors via regulation of FOXO1 transcriptional activity and accumulation of p27Kip1.
The scavenging of superoxide radicals promotes apoptosis induced by a novel cell-permeable fusion protein, sTRAIL:FeSOD, in tumor necrosis factor-related apoptosis-inducing ligand-resistant leukemia cells
Authors: Tang Hongyun , Qin Yong , Li Jianyong , Gong Xingguo 
Published: March 2011

Abstract

Background
Many cancer cells develop resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, necessitating combination with chemotherapy, and normal cells manifest side effects due to the combined treatment regimen of TRAIL and chemotherapeutic drugs. A novel cancer therapy utilizing TRAIL is thus urgently needed.

Results
In this study, we exploited TRAIL receptor-mediated endocytosis for the first time to produce a cell-permeable molecule, soluble forms of recombinant TRAIL:iron superoxide dismutase (sTRAIL:FeSOD), which possesses sTRAIL-induced apoptotic ability and FeSOD antioxidant activity. The FeSOD component was rapidly introduced into the cell by sTRAIL and intracellular superoxide radical (O2
-), which have been implicated as potential modulators of apoptosis in cancer cells, was eliminated, resulting in a highly reduced cellular environment. The decrease in cellular O2
-, which was accompanied by a brief accumulation of H2O2 and downregulation of phosphorylated Akt (p-Akt) and cellular FLICE-inhibitory protein, sensitized K562 leukemia cells and human promyelocytic leukemia (HL-60) cells to TRAIL-induced apoptosis. The low H2O2 levels protected human LO2 hepatocytes from sTRAIL:FeSOD-induced apoptosis despite downregulation of p-Akt. We also obtained evidence that the lack of response to sTRAIL:FeSOD in normal T cells occurred because sTRAIL:FeSOD shows much stronger shifts of redox state in erythroleukemia (K562) and HL-60 cells compared to that in normal T cells. K562 and HL-60 cells underwent sTRAIL:FeSOD-induced apoptosis without the dysfunction of mitochondria.

Conclusions
The fusion protein overcomes the inability of FeSOD to permeate the cell membrane, exhibits synergistic apoptotic effects on K562 and HL-60 cells and demonstrates minimal toxicity to normal T cells and the normal liver cell line LO2, indicating its potential value for the treatment of leukemia.
Eschar and neck lymphadenopathy caused by Francisella tularensis after a tick bite: a case report
Authors: Edouard Sophie , Gonin Khira , Turc Yves , Angelakis Emmanouil , Socolovschi Cristina , Raoult Didier 
Published: March 2011

Abstract

Introduction
In 25 to 35% of cases, the aetiological agent of scalp eschar and neck lymphadenopathy after a tick bite remains undetermined. To date, Rickettsia slovaca, Rickettsia raoultii and more recently Bartonella henselae have been associated with this syndrome.

Case presentation
A four-year-old Caucasian boy was admitted to hospital with fever, vomiting and abdominal pain. On physical examination, an inflammatory and suppurating eschar was seen on the scalp, with multiple enlarged cervical lymph nodes on both sides. Although no tick was found in this scalp lesion, a diagnosis of tick-borne lymphadenopathy was suggested, and explored by serology testing and polymerase chain reaction of a biopsy from the eschar. Francisella tularensis DNA was found in the skin biopsy and the serology showed titres consistent with tularaemia.

Conclusion
This is, to the best of our knowledge, the first reported case of scalp eschar and neck lymphadenopathy after tick bite infection caused by F. tularensis.
Adalimumab - an effective and promising treatment for patients with fistulizing Crohn's disease: a case series
Authors: Kouklakis George , Efremidou Eleni I , Zezos Peter , Liratzopoulos Nikolaos , Souftas Vassilios D , Gatopoulou Anthia , Simopoulos Konstantinos , Manolas Konstantinos J 
Published: March 2011

Abstract

Introduction
Crohn's disease is a chronic inflammatory bowel disease of unknown etiology which may affect any part of the bowel. Fistulas are a common and often serious complication of Crohn's disease. The treatment for fistulizing Crohn's disease can be medical, surgical or a combination of the two. Recently, adalimumab, a fully human anti-tumor necrosis factor monoclonal antibody, has been suggested as a safe and effective treatment for the induction and maintenance of remission in adult patients with moderate to severe Crohn's disease, who are refractory to conventional therapy or intolerant to infliximab. However, large studies focusing on evaluating the efficacy of adalimumab in fistulizing Crohn's disease have not yet been published.

Case presentation
We report the cases of three patients, of European Caucasian ethnicity and Greek nationality, with active luminal and fistulizing Crohn's disease. All of the cases were treated successfully with adalimumab. Patient 1 (a 44-year-old man) and patient 2 (an 18-year-old woman) developed early post-surgical enterocutaneous fistulas, while patient 3 (a 20-year-old woman) had peri-anal fistulizing Crohn's disease. Adalimumab treatment (160 mg subcutaneously at week zero, 80 mg at week two, and 40 mg every other week) was used for three different indications: (1) after the failure of other conservative medical treatments for Crohn's disease (patient 1); (2) as a monotherapy in treating a naive patient (patient 2); (3) after an intolerance to infliximab (patient 3). A remission of the active luminal and fistulizing disease was achieved soon after the initiation of adalimumab and sustained thereafter with maintenance doses. No further surgical intervention was required and no adverse effects were observed in any of the cases.

Conclusions
Fistulizing Crohn's disease remains a challenge in clinical practice. Adalimumab seems to be an effective, well-tolerated and safe treatment option for the induction and maintenance of remission in patients with moderate to severe peri-anal fistulizing Crohn's disease. Furthermore, adalimumab seems to be a promising treatment option for patients with moderate to severe fistulizing Crohn's disease with enterocutaneous fistulas. However, this clinical observation needs to be investigated in further clinical trials.
Abscopal effect of radiation on lung metastases of hepatocellular carcinoma: a case report
Authors: Okuma Kae , Yamashita Hideomi , Niibe Yuzuru , Hayakawa Kazushige , Nakagawa Keiichi 
Published: March 2011

Abstract

Introduction
The abscopal effect is the effect of radiation therapy at a site distant to the area of irradiation. This is not a common event and has not been clearly defined, resulting in few reported cases in the literature. We discuss this phenomenon in a patient with hepatocellular carcinoma.

Case presentation
A 63-year-old Japanese man underwent extended right hepatic lobectomy for hepatocellular carcinoma. During his follow-up examination, a single lung metastasis and a single mediastinal lymph node metastasis were found. Trans-catheter arterial embolization was initially attempted to treat the mediastinal tumor, however this approach failed to take effect and carried risks of spinal artery embolism. External-beam irradiation, with a dose of 2.25 Gy per fraction, was performed using an antero-posterior parallel-opposed technique (total dose, 60.75 Gy). A computed tomography scan performed one month after starting radiotherapy showed a remarkable reduction of the mediastinal lymph node metastasis. In addition to this, we observed spontaneous shrinking of the lung metastasis, which was located in the right lower lobe and out of the radiation field. No chemotherapy was given during the period. There has been no recurrence of either the lung metastasis or the mediastinal lymph node metastasis during a follow-up 10 years after the radiotherapy.

Conclusion
We observed a rare abscopal effect in a site distant from the area of irradiation. Irradiation of the mediastinum resulted in tumor mass regression in the untreated lung tumor.
Use of Oxalic Acid-Modified Rice Husk for the Adsorption of Neutral Red from Aqueous Solutions
Authors: Zou Weihua , Bai Hongjuan , Li Ke , Shi Xiaolan , Han Runping 
Published: March 2011

Rice husk modified with oxalic acid (MRH) was tested as a lowcost adsorbent for the removal of Neutral Red (NR) dye from aqueous solutions employing batch adsorption procedures. Such studies were conducted by varying various parameters such as the pH, the adsorbent dosage, the salt concentration, the contact time, the concentration of the adsorbate and the temperature. The kinetic experimental data were analyzed using three kinetic equations, viz. the pseudo-first-order equation, the pseudo-second-order equation and the intra-particle diffusion model equation, to examine the mechanism of adsorption and the potential rate-controlling step. The mechanism of the process was found to be complex, consisting of both surface adsorption and pore diffusion. The values of the effective diffusion parameter, Deff, were estimated to be of the order of 10−8 cm2/s, indicated that intra-particle diffusion was not the rate-controlling step. The equilibrium adsorption data obtained at various temperatures were analyzed using the Langmuir, Freundlich and Redlich–Peterson isotherm models using non-linear regressive analysis. The equilibrium adsorption results were better fitted by the Langmuir and Redlich–Peterson isotherms relative to the Freundlich model. Calculated thermodynamic parameters showed that the adsorption of NR onto MRH was feasible, spontaneous and endothermic under the studied conditions. The carboxyl groups on the surface of the modified rice husk (MRH) were primarily responsible for the sorption of NR. It is suggested that MRH may be suitable as an adsorbent material for adsorbing NR from aqueous solutions.
An Integer Optimization Approach to Large-Scale Air Traffic Flow Management
Authors: Bertsimas Dimitris , Lulli Guglielmo , Odoni Amedeo 
Published: March 2011

This paper presents a new integer programming (IP) model for large-scale instances of the air traffic flow management (ATFM) problem. The model covers all the phases of each flight—i.e., takeoff, en route cruising, and landing—and solves for an optimal combination of flow management actions, including ground-holding, rerouting, speed control, and airborne holding on a flight-by-flight basis. A distinguishing feature of the model is that it allows for rerouting decisions. This is achieved through the imposition of sets of “local” conditions that make it possible to represent rerouting options in a compact way by only introducing some new constraints. Moreover, three classes of valid inequalities are incorporated into the model to strengthen the polyhedral structure of the underlying relaxation. Computational times are short and reasonable for practical application on problem instances of size comparable to that of the entire U.S. air traffic management system. Thus, the proposed model has the potential of serving as the main engine for the preliminary identification, on a daily basis, of promising air traffic flow management interventions on a national scale in the United States or on a continental scale in Europe.
Strategic Design and Analysis of a Relay Network in Truckload Transportation
Authors: Üster Halit , Kewcharoenwong Panitan 
Published: March 2011

The truckload industry faces a serious and chronic problem of high driver turnover rate—typically more than 100%—with staggering associated costs. Among the major causes of this problem are extended on-the-road times where drivers handle several truckload pickup and deliveries successively; nonregular schedules and get-home rates; and low utilization, i.e., less mileage/unit-time per driver, which leads to low pay. We consider the strategic design of a relay network that may potentially help to alleviate this problem by providing an efficient underlying network that facilitates an assignment of drivers to home bases (domiciles to which they stay close) and generation of more predictable schedules with continuity and higher get-home rates. In relay network design, we are interested in determining a number of relay point locations, assigning network nodes to these relay points (i.e., defining domiciles), and determining the actual route (from the origin to the destination) for each truckload on the network. In doing so, we explicitly consider driver tour lengths, load imbalance at relay points, and the percentage circuity constraints. We develop an efficient Benders' decomposition-based algorithm that is significantly enhanced via strengthened Benders' cuts, cut disaggregation schemes, heuristics for improved upper bounds, and surrogate constraints. Our approach provides the ability to solve large size instances within reasonable solution times and very small optimality gaps. We also examine the effects of changes in the problem parameters on the performance of solution algorithms. Furthermore, in our computational experiments, we provide an analysis of the conditions for which relay network presents most benefits as well as incorporation of direct shipments within relay network operations.
Experimental investigation of stress wave propagation in standing trees
Authors: Zhang Houjiang , Wang Xiping , Su Juan 
Published: March 2011

Abstract
The objective of this study was to investigate how a stress wave travels in a standing tree as it is introduced into the tree trunk through a mechanical impact. A series of stress wave time-of-flight (TOF) data were obtained from three freshly-cut red pine (Pinus resinosa Ait.) logs by means of a two-probe stress wave timer. Two-dimensional (2D) and three-dimensional (3D) stress wave contour maps were constructed based on the experimental data using a commercial software. These stress wave contour maps represent the wave fronts in a time sequence, illustrating the flow of stress wave energy within a log. The analysis of TOF data and wave fronts indicates that stress wave propagation in standing trees is affected by tree diameter, travel distance, and internal wood conditions (wood properties and structural defects). When a stress wave is introduced into a tree trunk from a point source, it initially propagates in the impact direction as a 3D wave. Then the flow of the stress wave energy gradually changes towards the longitudinal directions. As the diameter-to-distance ratio reaches 0.1 or below, the wave begins to travel as a quasi 1D wave.
Microbiologic Results After Non‐Surgical Erbium‐Doped:Yttrium, Aluminum, and Garnet Laser or Air‐Abrasive Treatment of Peri‐Implantitis: A Randomized Clinical Trial
Authors: Persson G. Rutger , Roos‐Jansåker Ann‐Marie , Lindahl Christel , Renvert Stefan 
Published: March 2011

Background: The purpose of this study is to assess clinical and microbiologic effects of the non‐surgical treatment of peri‐implantitis lesions using either an erbium‐doped:yttrium, aluminum, and garnet (Er:YAG) laser or an air‐abrasive subgingival polishing method.Methods: In a 6‐month clinical trial, 42 patients with peri‐implantitis were treated at one time with an Er:YAG laser or an air‐abrasive device. Routine clinical methods were used to monitor clinical conditions. Baseline and 6‐month intraoral radiographs were assessed with a software program. The checkerboard DNA–DNA hybridization method was used to assess 74 bacterial species from the site with the deepest probing depth (PD) at the implant. Non‐parametric tests were applied to microbiology data.Results: PD reductions (mean ± SD) were 0.9 ± 0.8 mm and 0.8 ± 0.5 mm in the laser and air‐abrasive groups, respectively (not significant). No baseline differences in bacterial counts between groups were found. In the air‐abrasive group, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus anaerobius were found at lower counts at 1 month after therapy (P <0.001) and with lower counts in the laser group for Fusobacterium nucleatum naviforme (P = 0.002), and Fusobacterium nucleatum nucleatum (P = 0.002). Both treatments failed to reduce bacterial counts at 6 months. Porphyromonas gingivalis counts were higher in cases with progressive peri‐implantitis (P <0.001).Conclusions: At 1 month, P. aeruginosa, S. aureus, and S. anaerobius were reduced in the air‐abrasive group, and Fusobacterium spp. were reduced in the laser group. Six‐month data demonstrated that both methods failed to reduce bacterial counts. Clinical improvements were limited.
Factors Associated With Dental Implant Survival: A 4‐Year Retrospective Analysis
Authors: Zupnik Jamie , Kim Soo‐woo , Ravens Daniel , Karimbux Nadeem , Guze Kevin 
Published: March 2011

Background: Dental implants are a predictable treatment option for replacing missing teeth and have strong survival and success outcomes. However, previous research showed a wide array of potential risk factors that may have contributed to dental implant failures. The objectives of this study are to study if implant survival rates were affected by known risk factors and risk indicators that may have contributed to implant failures. The secondary outcome measures were whether the level of expertise of the periodontal residents affected success rates and how the rate of implant success at the Harvard School of Dental Medicine (HSDM) compared to published standards.Methods: A retrospective chart review of patients at the HSDM who had one of two types of rough‐surface implants (group A or B) placed by periodontology residents from 2003 to 2006 was performed. Demographic, health, and implant data were collected and analyzed by multimodel analyses to determine failure rates and any factors that may have increased the likelihood of an implant failure.Results: The study cohort included 341 dental implants. The odds ratio for an implant failure was most clearly elevated for diabetes (2.59 implant surface group B (7.84), and male groups (4.01). There was no significant difference regarding the resident experience. The success rate for HSDM periodontology residents was 96.48% during the 4‐year study period.Conclusions: This study demonstrates that implant success rates at HSDM fell within accepted published standards, confirmed previously identified risk factors for a failure, and potentially suggested that other acknowledged risk factors could be controlled for. Furthermore, the level of experience of the periodontology resident did not have an impact on survival outcomes.
iNOS‐Derived Nitric Oxide Stimulates Osteoclast Activity and Alveolar Bone Loss in Ligature‐Induced Periodontitis in Rats
Authors: Herrera Bruno S. , Martins‐Porto Rodrigo , Maia‐Dantas Aline , Campi Paula , Spolidorio Luis C. , Costa Soraia K.P. , Van Dyke Thomas E. , Gyurko Robert , Muscara Marcelo N. 
Published: March 2011

Background: Inflammatory stimuli activate inducible nitric oxide synthase (iNOS) in a variety of cell types, including osteoclasts (OC) and osteoblasts, resulting in sustained NO production. In this study, we evaluate the alveolar bone loss in rats with periodontitis under long‐term iNOS inhibition, and the differentiation and activity of OC from iNOS‐knockout (KO) mice in vitro.Methods: Oral aminoguanidine (an iNOS inhibitor) or water treatment was started 2 weeks before induction of periodontitis. Rats were sacrificed 3, 7, or 14 days after ligature placement, and alveolar bone loss was evaluated. In vitro OC culture experiments were also performed to study the differentiation of freshly isolated bone marrow cells from both iNOS KO and wild‐type C57BL/6 mice. OC were counted 6 days later after tartrate‐resistant acid phosphatase staining (a marker of osteoclast identity), and bone resorption activity was assessed by counting the number of resorption pits on dentin disks.Results: Rats with ligature showed progressive and significant alveolar bone loss compared to sham animals, and aminoguanidine treatment significantly inhibited ligature‐induced bone loss at 7 and 14 days after the induction. In comparison to bone marrow cells from wild‐type mice, cells from iNOS KO mice showed decreased OC growth and the resulting OC covered a smaller culture dish area and generated fewer resorption pit counts.Conclusion: Our results demonstrate that iNOS inhibition prevents alveolar bone loss in a rat model of ligature‐induced periodontitis, thus confirming that iNOS‐derived NO plays a crucial role in the pathogenesis of periodontitis, probably by stimulating OC differentiation and activity.