bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sorafenib Overcomes Irinotecan Resistance in Colorectal Cancer by Inhibiting the ABCG2 Drug-Efflux Pump
Authors: Mazard Thibault , Causse Annick , Simony Joelle , Leconet Wilhem , Vezzio-Vie Nadia , Torro Adeline , Jarlier Marta , Evrard Alexandre , Del Rio Maguy , Assenat Eric , Martineau Pierre , Ychou Marc , Robert Bruno , Gongora Celine 
Published: August 2013

Abstract
Despite recent advances in the treatment of colorectal cancer (CRC), tumor resistance is a frequent cause of chemotherapy failure. Therefore, new treatment options are needed to improve survival of patients with irinotecan-refractory CRCs, particularly those bearing KRAS mutations that preclude the use of anti-EGFR therapies. In this study, we investigated whether sorafenib could reverse irinotecan resistance, thereby enhancing the therapeutic efficacy of routinely used irinotecan-based chemotherapy. We used both in vitro (the HCT116, SW48, SW620, and HT29 colon adenocarcinoma cell lines and four SN-38–resistant HCT-116 and SW48 clones) and in vivo models (nude mice xenografted with SN-38–resistant HCT116 cells) to test the efficacy of sorafenib alone or in combination with irinotecan or its active metabolite, SN-38. We have shown that sorafenib improved the antitumoral activity of irinotecan in vitro, in both parental and SN-38–resistant colon adenocarcinoma cell lines independently of their KRAS status, as well as in vivo, in xenografted mice. By inhibiting the drug-efflux pump ABCG2, sorafenib favors irinotecan intracellular accumulation and enhances its toxicity. Moreover, we found that sorafenib improved the efficacy of irinotecan by inhibiting the irinotecan-mediated p38 and ERK activation. In conclusion, our results show that sorafenib can suppress resistance to irinotecan and suggest that sorafenib could be used to overcome resistance to irinotecan-based chemotherapies in CRC, particularly in KRAS-mutated tumors. Mol Cancer Ther; 12(10); 2121–34. ©2013 AACR.
Berbamine Inhibits the Growth of Liver Cancer Cells and Cancer-Initiating Cells by Targeting Ca2+/Calmodulin-Dependent Protein Kinase II
Authors: Meng Zhipeng , Li Tao , Ma Xiaoxiao , Wang Xiaoqiong , Van Ness Carl , Gan Yichao , Zhou Hong , Tang Jinfen , Lou Guiyu , Wang Yafan , Wu Jun , Yen Yun , Xu Rongzhen , Huang Wendong 
Published: August 2013

Abstract
Liver cancer is the third leading cause of cancer deaths worldwide but no effective treatment toward liver cancer is available so far. Therefore, there is an unmet medical need to identify novel therapies to efficiently treat liver cancer and improve the prognosis of this disease. Here, we report that berbamine and one of its derivatives, bbd24, potently suppressed liver cancer cell proliferation and induced cancer cell death by targeting Ca2+/calmodulin-dependent protein kinase II (CAMKII). Furthermore, berbamine inhibited the in vivo tumorigenicity of liver cancer cells in NOD/SCID mice and downregulated the self-renewal abilities of liver cancer–initiating cells. Chemical inhibition or short hairpin RNA–mediated knockdown of CAMKII recapitulated the effects of berbamine, whereas overexpression of CAMKII promoted cancer cell proliferation and increased the resistance of liver cancer cells to berbamine treatments. Western blot analyses of human liver cancer specimens showed that CAMKII was hyperphosphorylated in liver tumors compared with the paired peritumor tissues, which supports a role of CAMKII in promoting human liver cancer progression and the potential clinical use of berbamine for liver cancer therapies. Our data suggest that berbamine and its derivatives are promising agents to suppress liver cancer growth by targeting CAMKII. Mol Cancer Ther; 12(10); 2067–77. ©2013 AACR.
Treatment of Chronic Maxillary Atelectasis Using Balloon Dilation
Authors: Sun Daniel Q. , Dubin Marc G. 
Published: August 2013

Balloon dilation may offer a more expedient and cost‐effective treatment method compared with traditional endoscopic sinus surgery for chronic maxillary atelectasis. We sought to demonstrate the feasibility of balloon dilation of the maxillary os as a treatment modality for patients with chronic maxillary atelectasis by investigating the short‐term outcomes in a retrospective case series of 4 patients representing 5 sinuses treated between 2011 and 2013. All sinuses were successfully balloon dilated without complications. Follow‐up ranged from 1 week to 4 months. Aeration of the treated sinuses without restenosis was confirmed by postoperative endoscopy, sinus computed tomography, or both. All patients reported subjective symptomatic improvement. Balloon dilation of the maxillary os may be a feasible treatment option for maxillary sinus atelectasis. Longer follow‐up and a larger study sample will be needed to validate the safety of this technique and determine the rate of restenosis.
Staplers versus hand-sewing for pulmonary lobectomy: randomized controlled trial
Authors: Tantraworasin Apichat , Seateang Somcharean , Bunchungmongkol Nutchanart 
Published: August 2013

Background division of the parenchymal lung for lobectomy is performed in patients who have an incomplete fissure. A stapler device can reduce postoperative air leak, but it is expensive. Objective to investigate the advantage of using a stapler, in terms of postoperative air leak and cost, compared to hand-sewn techniques. Method a non-blinded randomized controlled trial was conducted in Chiang Mai University Hospital, Thailand, from November 15, 2011 to September 30, 2012. Fifty-three adult patients were randomized to undergo a hand-sewn technique (27 patients) or stapler closure (26 patients). Results postoperative air leak in the stapler group was less than that in the hand-sewn group (7.7% vs. 29.6%, p = 0.044), and the duration of air leak in the stapler group was significantly shorter than that in the hand-sewn group (1.0 vs. 13.4 days, p = 0.032). The cost of treatment was not significantly different between groups; however, the total cost in the stapler group was less than that in the hand-sewn group (mean difference 4454 Thai baht (US$144.75). Conclusion a stapler reduces postoperative air leaks and the duration of air leaks. Furthermore, the total cost of treatment was comparable. Therefore, using staples may provide substantial financial benefits.
Progression of Osteoarthritis After Double- and Single-Bundle Anterior Cruciate Ligament Reconstruction
Authors: Song Eun-Kyoo , Seon Jong-Keun , Yim Ji-Hyeon , Woo Seong-Hwan , Seo Hyoung-Yeon , Lee Keun-Bae 
Published: August 2013

Background: No consensus has been reached on the advantages of double-bundle (DB) anterior cruciate ligament reconstruction (ACLR) over the single-bundle (SB) technique, particularly with respect to the prevention of osteoarthritis (OA) after ACLR. Purpose: To evaluate whether DB ACLR has any advantages in the prevention of OA or provides better stability and function after ACLR compared with the SB technique. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 130 patients with an ACL injury in one knee were prospectively randomized into a DB group (n = 65) or an SB group (n = 65). For the radiologic evaluation, we determined the degree of OA based on the Kellgren-Lawrence grade before the operation and at the time of the final follow-up and determined the number of patients with progression of OA more than one grade from pre- to postoperation. We evaluated the stability results using the Lachman and pivot-shift tests and stress radiography. We also compared the functional outcomes based on the Lysholm knee score, Tegner activity score, and International Knee Documentation Committee (IKDC) subjective scale. Results: Six patients (4 in the DB group and 2 in the SB group) suffered graft failure during the follow-up and had ACL revision surgery ( P = .06). A total of 112 patients were observed for a minimum of 4 years (DB group, n = 52; SB group, n = 60). Five patients (9.6%) in the DB group and 6 patients (10%) in the SB group had more advanced OA at the final follow-up ( P = .75). All patients recovered full range of motion within 6 months from surgery. Stability results of the Lachman test, pivot-shift test, and the radiographic stability test failed to reveal any significant intergroup differences ( P = .37, .27, and .67, respectively). In the pivot-shift result, the DB group had 4 patients with grade 2 and the SB group had 3 patients with grade 2 ( P = .27). Clinical outcomes, including Lysholm knee and Tegner activity scores, were similar in the 2 groups. Statistical significance was achieved only for the IKDC subjective scale (78.2 in DB group vs 73.1 in SB group; P = .03). Conclusion: The DB technique, compared with SB, was not more effective in preventing OA and did not have a more favorable failure rate. Although the DB ACLR technique produced a better IKDC subjective scale result than did the SB ACLR technique, the 2 modalities were similar in terms of clinical outcomes and stability after a minimum 4 years of follow-up.
Targeted therapies in systemic lupus erythematosus
Authors: Grech P , Khamashta MA 
Published: August 2013

Systemic lupus erythematosus (SLE) is a chronic, multisystem disorder characterised by loss of tolerance to endogenous nuclear antigens and autoantibody formation. Recent insight into the immunopathogenesis of lupus has provided the foundation for a novel class of agents which target specific, dysregulated components of the immune system. Efforts have focused predominantly on B-cell depleting therapies, of which belimumab was the first to demonstrate success in phase III studies and thus receive marketing authorisation. Off-label prescribing of rituximab in refractory cases is common and supported by uncontrolled studies, which suggest a favourable risk:benefit profile. However, two placebo-controlled trials failed to show benefit, possibly because of inappropriate patient selection and other aspects of trial methodology. Inhibition of dysregulated co-stimulatory signals and cytokines are other therapeutic strategies currently under investigation. Some candidate drugs failed to meet primary endpoints in early-phase clinical trials, yet demonstrated clinical benefit when alternative assessment criteria were applied or specific patient sub-groups analysed. Well-designed studies of greater size and duration are needed to clarify the therapeutic utility of these agents. Future immunomodulatory strategies targeting interferon-alpha, T cells, oxidative stress and epigenetic abnormalities may reduce multisystem disease activity and prolong survival in this complex and heterogeneic disease.
Validation and evaluation of the German Brief Index of Lupus Damage (BILD) – a self-reported instrument to record damage in systemic lupus erythematosus
Authors: Chehab G , Sander O , Richter J , Acar H , Vordenbäumen S , Brinks R , Schneider M , Fischer-Betz R 
Published: August 2013

Introduction Damage is a very important predictor for outcome in systemic lupus erythematosus (SLE) and should be routinely documented. Patient-reported assessments for damage are rare and neither the Lupus Damage Index Questionnaire (LDIQ) nor the Brief Index of Lupus Damage (BILD) is validated in German language. Our aim was to validate the BILD in German language and evaluate its use as a patient-administered instrument. Method We translated and adapted the BILD questionnaire to use it as a self-administered questionnaire for German-speaking SLE patients. It was applied to SLE outpatients at an academic centre and compared to the SLICC/SDI and other lupus outcome parameters. Results The German BILD showed as strong a correlation with the SLICC/SDI as the original version of the BILD and a superior correlation compared to the LDIQ. It scored significantly higher with an increase of age, disease duration or disease activity, with a lower functional status or overall health and a higher probability of receiving an incapacity pension. Conclusion The German version of the BILD shows a comparable validity to the original BILD with even higher correlation to physician-reported damage even when used as a self-administered questionnaire. Hence it represents a promising instrument to survey damage in clinical routine as well as in clinical and epidemiological studies.
Outcome of 132 Consecutive Reconstructive Operations for Intestinal Fistula—Staged Operation Without Primary Anastomosis Improved Outcome in Retrospective Analysis
Authors: Runström B. , Hallböök O. , Nyström PO. , Sjödahl R. , Olaison G. 
Published: August 2013

Aim: To study factors that influenced healing and survival after attempted closure of enterocutaneous fistula. Material and Methods: Retrospective analysis of prospective data concerning 101 patients operated on 132 instances for 110 enterocutaneous fistulae at two hospitals. Results: In all, 96 (87%) of the 110 fistulae healed and 92 (91%) patients survived. A total of 9 patients with unhealed fistula died. Multivariate analysis revealed jaundice as an independent factor for both death and failed closure and operation without anastomosis as an independent positive factor for healing. Failure rate was lower after an operation with stoma without anastomosis (6 of 43, 14%) than after an operation with anastomosis (30 of 89, 34%) p = 0.0213. Of the 36 instances with unhealed fistula, 13 (36%) could be ascribed to inadvertent bowel lesions at the reconstructive operation. In addition, univariate analysis revealed that patients with previous multiple laparotomies or with multiple operations for enterocutaneous fistula healed less likely and had higher mortality. A low serum albumin, high white blood cell count, high C-reactive protein concentration, high fistula output, total parenteral nutrition, and operation for recurrent fistula were associated with death together with long operation time and operative bleeding, both indicators of surgical complexity. Over time, staged surgery avoiding anastomosis increased from 27% to 57%. Mortality decreased from 12% to 6%, and healing increased from 73% to 94%. Conclusions: Chronic inflammation, malnutrition, and liver failure causing an impaired healing capacity are important reasons for failure. Staged operation without primary anastomosis may allow the patient to reverse this condition and improve outcome. The high surgical complexity is a negative factor that requires careful planning of the operation.
Extraumbilical Single-Incision Laparoscopic Cholecystectomy with Standard Laparoscopic Instruments
Authors: Oruc M.T. , Ugurlu M. U. 
Published: August 2013

Background and Aim: Single-incision laparoscopic surgery is a rapidly progressing field as it combines some advantages such as cosmesis and less incisional pain. However, it also has some disadvantages such as limitation of movement and clashing of the hand instruments, which increase the complexity and technical challenges of the operation. In this study, we describe a pilot trial of single-incision laparoscopic cholecystectomy through a paramedian access site. Material and Methods: A total of 25 patients underwent single-incision laparoscopic cholecystectomy with this method. Acute cases with empyema and patients with history of previous abdominal surgery were excluded. Single-incision is established on the right upper quadrant, right latero-superior of the umbilicus, so that trocar sites and projection of the gallbladder on the abdominal wall are on the same vertical line. Standard laparoscopic instruments were placed into the abdominal cavity providing triangulation. Once the laparoscope, grasper, and dissector are in place, the overall procedures are similar to the standard laparoscopic cholecystectomy. Results: Single-incision laparoscopic cholecystectomy through an extraumbilical access site was successfully completed in all 25 patients without conversion to open surgery. Additional skin incisions and trocar access were required only in two patients. The mean operative time was 39.3 min (range: 20–75 min). The mean body mass index was 27.2. Postoperative course was uneventful in all patients. The mean postoperative hospital stay was shorter than 24 h, and all patients were discharged at first day postoperatively. No postoperative complications including seroma, wound infection, and trocar-site hernia were observed at 6-month follow-up. Conclusion: We described a new access site for single-incision laparoscopic cholecystectomy using standard laparoscopic instruments. We believe that this type of access site overcomes the technical difficulties of performing single-incision laparoscopic cholecystectomy, and it is a promising alternative method for the treatment of patients with symptomatic gallstone disease as a minimal invasive abdominal surgery.
Effect of Active Versus Passive Recovery on Performance During Intrameet Swimming Competition
Authors: Hinzpeter Jaime , Zamorano Álvaro , Cuzmar Diego , Lopez Miguel , Burboa Jair 
Published: August 2013

Background: During competition, high-performance swimmers are subject to repeated physical demands that affect their final performance. Measurement of lactate concentration in blood seeks to indirectly gauge physiologic responses to the increase in physical exercise. Swimmers face multiple maximal-exertion events during competition. Strenuous physical exercise leads to fatigue and, thus, a decrease in sports performance. Hypothesis: Regeneration exercises in swimming increase the clearance of blood lactate and therefore improve athletic performance within a single day of competition. Study Design: Crossover study. Level of Evidence: Level 1. Methods: Of 25 swimmers, 21 were included, with a mean age of 17 years. They performed exercises that increased blood lactate on 2 days. The protocol was a warm-up, followed by a 100-m freestyle workout at full speed. Swimming exercises followed that were increasingly demanding, during which serial lactatemia measurements were taken. On the first day, regeneration exercises were performed; on the second day, the swimmers rested. Next, lactatemia was measured, and a timed 100-m freestyle workout was performed at maximum speed. Results: The stress exercises increased the mean lactate concentration by 4.6 mmol/L, which corresponds to 78% of the initial basal level. The postregeneration lactatemia level was lower than that after resting (mean, 2.76 vs 6.51 mmol/L). The time to swim 100 m after regeneration was 68.11 seconds, while that after rest was 69.31 seconds. Conclusion: Blood lactate levels rose by up to 78% after the intensity of the training sessions was progressively increased. Regeneration exercises increased the rate in which blood lactate dissipated, in comparison with passive recuperation. The rate of lactate dissipation for regeneration exercises was 68%. This factor may have improved the physical performance of swimmers. Clinical Relevance: Regeneration exercises improved the performance of swimmers in maximal-exertion competition in a single day. The blood lactate level correlated with physical exercise load.
Requirement for Rictor in homeostasis and function of mature B lymphoid cells
Authors: Lee Keunwook , Heffington Lindsey , Jellusova Julia , Nam Ki Taek , Raybuck Ariel , Cho Sung Hoon , Thomas James W. , Rickert Robert C. , Boothby Mark 
Published: August 2013

Key PointsMaturation, homeostasis, and function of peripheral B lymphoid cells require Rictor, an essential mTOR complex 2 component. Rictor regulates survival of B cells and their balance of proapoptotic vs antiapoptotic gene expression.
Mapping the sex determination locus in the Atlantic halibut (Hippoglossus hippoglossus) using RAD sequencing
Authors: Palaiokostas Christos , Bekaert Michaël , Davie Andrew , Cowan Mairi E , Oral Münevver , Taggart John B , Gharbi Karim , McAndrew Brendan J , Penman David J , Migaud Hervé 
Published: August 2013

Abstract

Background
Atlantic halibut (Hippoglossus hippoglossus) is a high-value, niche market species for cold-water marine aquaculture. Production of monosex female stocks is desirable in commercial production since females grow faster and mature later than males. Understanding the sex determination mechanism and developing sex-associated markers will shorten the time for the development of monosex female production, thus decreasing the costs of farming.

Results
Halibut juveniles were masculinised with 17 α-methyldihydrotestosterone (MDHT) and grown to maturity. Progeny groups from four treated males were reared and sexed. Two of these groups (n = 26 and 70) consisted of only females, while the other two (n = 30 and 71) contained balanced sex ratios (50% and 48% females respectively). DNA from parents and offspring from the two mixed-sex families were used as a template for Restriction-site Associated DNA (RAD) sequencing. The 648 million raw reads produced 90,105 unique RAD-tags. A linkage map was constructed based on 5703 Single Nucleotide Polymorphism (SNP) markers and 7 microsatellites consisting of 24 linkage groups, which corresponds to the number of chromosome pairs in this species. A major sex determining locus was mapped to linkage group 13 in both families. Assays for 10 SNPs with significant association with phenotypic sex were tested in both population data and in 3 additional families. Using a variety of machine-learning algorithms 97% correct classification could be obtained with the 3% of errors being phenotypic males predicted to be females.

Conclusion
Altogether our findings support the hypothesis that the Atlantic halibut has an XX/XY sex determination system. Assays are described for sex-associated DNA markers developed from the RAD sequencing analysis to fast track progeny testing and implement monosex female halibut production for an immediate improvement in productivity. These should also help to speed up the inclusion of neomales derived from many families to maintain a larger effective population size and ensure long-term improvement through selective breeding.