bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of dietary supplementation of selenium and iodine on growth performance, carcass characteristics and histology of thyroid gland in goats
Authors: Aghwan Zeiad Amjad , Sazili Awis Qurni , Kadhim Khalid Kamil , Alimon Abdul Razak , Goh Yong Meng , Adeyemi Kazeem Dauda 
Published: November 2015

AbstractThis study assessed the effects of dietary selenium (Se), iodine (I) and a combination of both on growth performance, thyroid gland activity, carcass characteristics and the concentration of iodine and selenium in Longissimus lumborum (LL) muscle in goats. Twenty‐four bucks were randomly assigned to four dietary treatments: control (CON), basal diet without supplementation, basal diet + 0.6 mg Se/kg dry matter (DM) (SS), 0.6 mg I/kg DM (IP), or combination of 0.6 mg/kg DM Se and 0.6 mg/kg DM I (SSIP) and fed for 100 days. Animals fed diet SSIP exhibited higher (P < 0.05) body weight and better feed conversion ratio (FCR) than those fed other diets. Dressing percentage of goats fed the supplemented diets was higher (P < 0.05) than that of the control. Carcasses from the IP group had higher (P < 0.05) total fat proportion than the SSIP group. The levels of both elements were significantly elevated (P < 0.05) in LL muscle in supplemented goats. Thyroid follicular epithelial cells of IP and SSIP animals were significantly higher than those of CON and SS groups. The study demonstrated that the combined Se and I dietary supplementation improves growth performance, carcass dressing percentage and increases the retention of Se and I in goat meat.
CD49d (ITGA4) expression is a predictor of time to first treatment in patients with chronic lymphocytic leukaemia and mutated IGHV status
Authors: Baumann Tycho , Delgado Julio , Santacruz Rodrigo , Martínez‐Trillos Alejandra , Rozman María , Aymerich Marta , López Cristina , Costa Dolors , Carrió Anna , Villamor Neus , Montserrat Emili 
Published: November 2015

SummaryWe investigated CD49d (also termed ITGA4) expression and its biological and clinical correlations in 415 patients with chronic lymphocytic leukaemia. CD49d expression was stable over the course of the disease. A high expression of CD49d (>30%) was found in 142/415 (34%) patients and was associated with progressive disease (advanced clinical stage, high serum lactate dehydrogenase or β2‐microglobulin levels; all p < 0·05) and aggressive disease biology (increased ZAP70 or CD38, unmutated IGHV, trisomy 12, mutations of NOTCH1 and SF3B1; all P < 0·05). A higher CD49d expression was also associated with a lower blood lymphocyte count and a higher number of lymphoid areas involved by the disease. Patients with high CD49d expression were treated more frequently (55% vs. 27%; P < 0·001) and earlier (median time to treatment [TTT] 65·4 months vs. not reached; P < 0·001) than those with low CD49d expression. However, no significant differences in response rates were observed. In the subgroup of patients with mutated IGHV, high CD49d expression was predictive of a shorter TTT while other markers, such as ZAP70 and CD38, were not. In conclusion, in this study CD49d expression correlated with high‐risk CLL biomarkers and proved to be useful for separating patients with mutated IGHV into two different prognostic groups.
miR‐490‐5p suppresses tumour growth in renal cell carcinoma through targeting PIK3CA
Authors: Chen Ke , Zeng Jin , Tang Kun , Xiao Haibing , Hu Junhui , Huang Chunhua , Yao Weimin , Yu Gan , Xiao Wei , Guan Wei , Guo Xiaolin , Xu Hua , Ye Zhangqun 
Published: November 2015

Background InformationDysregulated micro‐RNAs have been reported in many human cancers, including renal cell carcinoma. Recent studies indicated that miR‐490 is involved in tumour development and progression. However, the expression profile and function in renal cell carcinoma remains unknown.ResultsHerein, we showed that miR‐490‐5p was down‐regulated in renal cell carcinoma tissues and cells compared with the adjacent normal tissues and normal cells. We also provided evidence that miR‐490‐5p acts as a tumour suppressor in renal carcinoma in a variety of in vitro and in vivo assays. Mechanistically, miR‐490‐5p was verified to directly bind to 3′ UTR of the PIK3CA mRNA and reduce the expression of PIK3CA at both mRNA and protein levels, which further inhibits phosphatidylinositol 3‐kinase/Akt signalling pathway. We further showed that knockdown of PIK3CA can block the growth inhibitory effect of miR‐490‐5p, and over‐expression of PIK3CA can reverse the inhibitory effect of miR‐490‐5p on renal cancer cell tumourigenicity.ConclusionsTaken together, our results indicated for the first time that miR‐490‐5p functions as a tumour suppressor in renal carcinoma by targeting PIK3CA.SignificanceOur findings suggest that miR‐490‐5p may be a potential gene therapy target for the treatment of renal cell carcinoma.
Mechanism of allosteric activation of TMEM16A/ANO1 channels by a commonly used chloride channel blocker
Authors: Ta Chau M , Adomaviciene Aiste , Rorsman Nils J G , Garnett Hannah , Tammaro Paolo 
Published: November 2015

Background and PurposeCalcium‐activated chloride channels (CaCCs) play varied physiological roles and constitute potential therapeutic targets for conditions such as asthma and hypertension. TMEM16A encodes a CaCC. CaCC pharmacology is restricted to compounds with relatively low potency and poorly defined selectivity. Anthracene‐9‐carboxylic acid (A9C), an inhibitor of various chloride channel types, exhibits complex effects on native CaCCs and cloned TMEM16A channels providing both activation and inhibition. The mechanisms underlying these effects are not fully defined.Experimental ApproachPatch‐clamp electrophysiology in conjunction with concentration jump experiments was employed to define the mode of interaction of A9C with TMEM16A channels.Key ResultsIn the presence of high intracellular Ca2+, A9C inhibited TMEM16A currents in a voltage‐dependent manner by entering the channel from the outside. A9C activation, revealed in the presence of submaximal intracellular Ca2+ concentrations, was also voltage‐dependent. The electric distance of A9C inhibiting and activating binding site was ~0.6 in each case. Inhibition occurred according to an open‐channel block mechanism. Activation was due to a dramatic leftward shift in the steady‐state activation curve and slowed deactivation kinetics. Extracellular A9C competed with extracellular Cl−, suggesting that A9C binds deep in the channel's pore to exert both inhibiting and activating effects.Conclusions and ImplicationsA9C is an open TMEM16A channel blocker and gating modifier. These effects require A9C to bind to a region within the pore that is accessible from the extracellular side of the membrane. These data will aid the future drug design of compounds that selectively activate or inhibit TMEM16A channels.
When and how should patients with multiple endocrine neoplasia type 1 be screened for thymic and bronchial carcinoid tumours?
Authors: Singh Ospina Naykky , Maraka Spyridoula , Montori Victor , Thompson Geoffrey B. , Young William F. 
Published: November 2015

SummaryPatients with multiple endocrine neoplasia type 1 (MEN1) are commonly evaluated for clinical manifestations of this syndrome with the rationale that early diagnosis and adequate treatment will result in improved survival and quality of life. Thymic and bronchial carcinoid tumours are uncommon but important manifestations of MEN1. Current practice guidelines recommend evaluation with computed tomography or magnetic resonance imaging scan of the chest every 1–2 years to detect these neoplasms. However, the certainty that patients will be better off (increased survival or quality of life) as a result of this case detection strategy is based on evidence at moderate–high risk of bias that yields only imprecise results of indirect relevance to these patients. In order to improve the care that patients with MEN1 receive, co‐ordinated efforts from different stakeholders are required so that large, prospective, multicentre studies evaluating patient important outcomes are carried out.
Anti‐hapten antibodies in response to skin sensitization
Authors: Singleton Helen , Popple Amy , Gellatly Nichola , Maxwell Gavin , Williams Jason , Friedmann Peter S. , Kimber Ian , Dearman Rebecca J. 
Published: November 2015

SummaryWhereas T lymphocyte (T cell) activation is the key event in the acquisition of skin sensitization and subsequent elicitation of allergic contact dermatitis, the humoral component of immune responses to organic contact allergens has received little consideration. There is evidence that, in experimental animals, topical exposure to potent contact allergens is associated with B cell activation and proliferation, and hapten‐specific antibody production. However, there is very limited evidence available for anti‐hapten antibody responses being induced following topical exposure of humans to contact allergens. Nevertheless, it is important to appreciate that there are almost no negative studies in which evidence for antibody production as the result of skin sensitization has been sought and not found. That is, there is absence of evidence rather than evidence of absence. Furthermore, exposure to chemical respiratory allergens, in which the skin has been implicated as a potential route of sensitization, results in anti‐hapten antibody responses. It is proposed that skin sensitization to contact allergens will normally be accompanied by antibody production. The phenomenon is worthy of investigation, as anti‐hapten antibodies could potentially influence and/or regulate the induction of skin sensitization. Moreover, such antibodies may provide an informative correlate of the extent to which sensitization has been acquired.
Incidence of prolonged postoperative ileus after colorectal surgery: a systematic review and meta‐analysis
Authors: Wolthuis A. M. , Bislenghi G. , Fieuws S. , de Buck van Overstraeten A. , Boeckxstaens G. , D'Hoore A. 
Published: November 2015

AbstractAimProlonged postoperative ileus (PPOI) after colorectal surgery remains a leading cause of delayed postoperative recovery and prolonged hospital stay. Its exact incidence is unknown. The aim of this systematic review is to investigate the definitions and incidence of PPOI previously described.MethodMEDLINE, Embase and the Cochrane Database of Systematic Reviews (up to July 2014) were searched. Two authors independently reviewed citations using predefined inclusion and exclusion criteria.ResultsThe search strategy yielded 3233 citations; 54 were eligible, comprising 18 983 patients. Twenty‐six studies were prospective [17 of these being randomized controlled trials (RCTs)] and 28 were retrospective. Meta‐analysis revealed an incidence of PPOI of 10.3% (95% CI 8.4–12.5) and 10.2% (95% CI 5.6–17.8) for non‐RCTs and RCTs, respectively. Significant heterogeneity was observed for both non‐RCTs and for RCTs. The used definition of PPOI, the type of surgery and access (laparoscopic, open) and the duration of surgery lead to significant variability of reported PPOI incidence between studies. The incidence of PPOI is lower after laparoscopic colonic resection.ConclusionThere is a large variation in the reported incidence of PPOI. A uniform definition of PPOI is needed to allow meaningful inter‐study comparisons and to evaluate strategies to prevent PPOI.
Anastomotic leakage after colon cancer resection: does the individual surgeon matter?
Authors: Marinello F. G. , Baguena G. , Lucas E. , Frasson M. , Hervás D. , Flor‐Lorente B. , Esclapez P. , Espí A. , García‐Granero E. 
Published: November 2015

AbstractAimAnastomotic leakage is one of the most feared complications after colonic resection. Many risk factors for anastomotic leakage have been reported, but the impact of an individual surgeon as a risk factor has scarcely been reported. The aim of this study was to assess if the individual surgeon is an independent risk factor for anastomotic leakage in colonic cancer surgery.MethodThis was a retrospective analysis of prospectively collected data from patients who underwent elective resection for colon cancer with anastomosis at a specialized colorectal unit from January 1993 to December 2010. Anastomotic leaks were diagnosed according to standardized criteria. Patient and tumour characteristics, surgical procedure and operating surgeons were analysed. A logistic regression model was used to discriminate statistical variation and identify risk factors for anastomotic leakage.ResultsA total of 1045 patients underwent elective colon cancer resection with primary anastomosis. Anastomotic leakage occurred in 6.4% of patients. Ileocolic anastomosis had an anastomotic leakage rate of 7.2%, colo‐colonic/colorectal anastomosis 5.2% and ileorectal anastomosis 12.7%, with intersurgeon variability. The independent risk factors associated with anastomotic leakage were the use of perioperative blood transfusion (OR 2.83, CI 1.59–5.06, P < 0.0001) and the individual surgeon performing the procedure (OR up to 8.44, P < 0.0001).ConclusionIn addition to perioperative blood transfusion, the individual surgeon was identified as an important risk factor for anastomotic leakage. Efforts should be made to reduce performance variability amongst surgeons.
WNT receptors profile expression in mature blood cells and immature leukemic cells: RYK emerges as a hallmark receptor of acute leukemia
Authors: Alvarez‐Zavala Monserrat , Riveros‐Magaña Alma R. , García‐Castro Beatriz , Barrera‐Chairez Esperanza , Rubio‐Jurado Benjamin , Garcés‐Ruíz Oscar M. , Ramos‐Solano Moisés , Aguilar‐Lemarroy Adriana , Jave‐Suarez Luis F. 
Published: November 2015

AbstractBackgroundWnt signaling induces a plethora of intracellular responses that dictate normal or abnormal cellular behavior. Abnormal WNT signaling has been related to the development of leukemogenic processes. In this regard, it is important to know the expression profile of WNT receptors in normal and malignant cells, in order to understand the WNT mechanisms that control the cell behavior. This work aimed to determine the WNT receptors expression profile in normal and leukemia cells.MethodsExpression of WNT receptors was determined by flow cytometry using leukemia‐derived cell lines, peripheral blood cells, and blood marrow samples from healthy volunteers and acute leukemia patients.ResultsDespite the heterogenic WNT receptors expression in mature normal blood cells and in immature tumorigenic cells, the RYK receptor was found highly express in leukemia cells, but not in normal cells. RYK expression was found mainly in cells positive to immature markers like CD33, CD13, CD7, and CD117.ConclusionsOur data show differences in FZD receptors expression between T and B leukemic cells, but both cell types and also myeloblast‐derived cells express high levels of RYK. The association of RYK expression with immature markers indicates its possible use as a diagnostic marker or therapeutic target.
Processing and MHC class II presentation of exogenous soluble antigen involving a proteasome‐dependent cytosolic pathway in CD40‐activated B cells
Authors: Becker Hans Jiro , Kondo Eisei , Shimabukuro‐Vornhagen Alexander , Theurich Sebastian , von Bergwelt‐Baildon Michael S. 
Published: November 2015

AbstractActivated B cells have the capacity to present antigen and induce immune responses as potent antigen‐presenting cells (APCs). As in other APCs, antigen presentation by B cells involves antigen internalization, antigen processing, and peptide loading onto MHC molecules. However, while the mechanism of antigen processing has been studied extensively in other APCs, this pathway remains elusive in B cells. The aim of this study was to investigate the MHC class II processing pathway in CD40‐activated B cells (CD40Bs), as a model for activated, antigen‐presenting B cells. Using CMV pp65 as a model antigen, we evaluated processing and presentation of the CD4 + T‐cell epitope 509‐523 (K509) by human CD40Bs in ELISPOT assays. As expected, stimulation of specific CD4 + T‐cell clones was attenuated after pretreatment of CD40Bs with inhibitors of classic class II pathway components. However, proteasome inhibitors such as epoxomicin limited antigen presentation as well. This suggests that the antigen is processed in a non‐classical, cytosolic MHC class II pathway. Further experiments with truncated protein variants revealed involvement of the proteasome in processing of the N and C extensions of the epitope. Access to the cytosol was shown to be size dependent. Epoxomicin sensitivity exclusively in CD40B cells, but not in dendritic cells, suggests a novel processing mechanism unique to this APC. Our data suggest that B cells process antigen using a distinct, non‐classical class II pathway.
Palmar process fractures of the distal phalanx in foals: A review
Authors: Faramarzi B. , Dobson H. 
Published: November 2015

SummaryDistal phalanx fractures are well documented in adult horses, but our knowledge of such fractures in foals is limited. Recent studies showed a high incidence of distal phalanx palmar process (PP) fractures in foals, the aetiology is not yet known. Several hypotheses have been suggested as possible causes, including uneven compressive forces, unequal forces from the deep digital flexor tendon, composition and shape of the PP, and conformation. A better understanding of the aetiology and predisposing factors requires further research. Radiography is the commonly used imaging modality for diagnosis of such fractures; however, those fractures might be missed on routine radiographic projections. In order to have a high probability of identifying fractures, a series of 5 radiographs including the oblique views is required. This article reviews the incidence of distal phalanx PP fractures and discusses the diagnosis of such fractures.
Von Willebrand disease in the emergency department
Authors: Livesey K. , Yealy D. M. , Li J. , Moore C. G. , Ragni M. V. 
Published: November 2015

SummaryBackgroundThe emergency department (ED) is often the first medical contact point for von Willebrand disease (VWD) patients experiencing acute conditions, notably bleeding. However, knowledge of VWD disease types and management options by ED providers is uncertain.AimTo determine the scope of VWD bleeding and treatment in the ED.MethodsWe evaluated medical record data in an IRB‐approved study from 922 notes accounting for 385 ER visits by 183 VWD patients from a single large institution's emergency department.ResultsOver half the ED visits were for an active or suspected bleed, the majority of which were associated with trauma, surgery, epistaxis, gastrointestinal bleeding or gynaecologic bleeding. By treatment, only 25% of all bleeds, including 77.8% of those with menorrhagia and 50.0% of those with epistaxis, received DDAVP or von Willebrand factor concentrate (VWF). The likelihood of receiving treatment was related to referral source, with the highest rates of treatment in patients referred by a haematologist.ConclusionsThese data suggest more patient and physician education are needed in managing patients with VWD, preferably at the time of diagnosis, including confirmation of the diagnosis, response to DDAVP testing, indication for DDAVP testing and formulation of a plan for suspected or actual bleeding.
Impact of being overweight on factor VIII dosing in children with haemophilia A
Authors: Henrard S. , Hermans C. 
Published: November 2015

IntroductionTreatment of haemophilia A (HA) requires infusions of factor VIII (FVIII) concentrates. The number of FVIII units infused to obtain a specific circulating FVIII level is calculated with the formula: [body weight (BW) (kg) × desired FVIII increase (%)]/2, with the assumption that each unit of FVIII infused per kg of BW increases the circulating FVIII level by 2%.AimThe aim of this study was to evaluate the impact of several morphometric parameters (BW, body mass index (BMI)‐for‐age, height), age and type of FVIII concentrate on FVIII recovery in children with HA.MethodsA total of 66 children aged between 10 and 18 with severe HA selected from six pharmacokinetic (PK) clinical trials using two recombinant FVIII concentrates were included in the analysis. Regression tree (RT) was used to identify predictors of FVIII recovery.ResultsThe median age was 14.5 years with a median FVIII recovery of 2.09 for all children. The median FVIII recovery was not significantly different between age groups. Two groups were created by RT: children with a BMI‐for‐age percentile <P95 (Median FVIII recovery: 1.94) and obese children with a BMI‐for‐age percentile ≥P95 (Median FVIII recovery: 2.65). The FVIII recovery was significantly different between these two groups (P < 0.001).ConclusionThese results are consistent with previous studies conducted in adults with HA and confirm that the long‐held and current practice of applying an arbitrary and universal recovery of two to the calculations of FVIII dosage should be abolished in both children and adults.
Taxanes‐induced cutaneous eruption: another histopathologic mimicker of malignancy
Authors: Prieto‐Torres L. , Llamas‐Velasco M. , Machan S. , Haro R. , de Asis S. , Carmo M. , Loredo A. , del Puerto C. , Fried I. , Kempf W. , Cerroni L. , Requena L. 
Published: November 2015

AbstractBackgroundPaclitaxel and docetaxel are antineoplastic drugs that bind the microtubules, producing the arrest of mitoses, which may be seen histopathologically. These histopathologic changes may simulate an intraepidermal keratinocytic malignant neoplasm, and an accurate diagnosis may be only established by clinicopathological correlation.ObjectivesWe report six cases of cutaneous eruptions by taxanes in which a striking cytotoxic effect was evident histopathologically.MethodsCutaneous biopsies were obtained in each patient.ResultsAtypical starburst‐like or ring‐like mitoses and dyskeratosis on basal and suprabasal layers of the epidermis. Areas of squamous syringometaplasia were also seen in one case.DiscussionThese findings were interpreted as expression of mitotic arrest due to taxanes. Similar changes have been described in association with other chemotherapeutic drugs such as vincristine, podophyllin and its derivative etoposide; colchicine, busulfan and maytansine, but cases like ours due to taxanes are exceptional or under‐reported.ConclusionDermatopathologists should be aware of these effects in order to interpret carefully cutaneous biopsy specimens of patients receiving taxanes.