bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidermal growth factor receptor‐tyrosine kinase inhibitor therapy is especially beneficial to patients with exon 19 deletion compared with exon 21 L858R mutation in non‐small‐cell lung cancer: Systematic review and meta analysis
Authors: Liu Yinghui , Ren Zuen , Wang Jinghui , Zhang Shucai 
Published: March 2016

AbstractBackgroundThe correlation between epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) and EGFR sensitive mutation subtypes in advanced or metastatic non‐small cell lung cancer (NSCLC) remains uncertain. We performed this meta‐analysis to determine different clinical outcomes between patients with exon 19 deletion accepting EGFR‐TKI therapy compared with those with exon 21 L858R mutation.MethodsPubMed and Web of Science were analyzed for eligible trials. Raw data were extracted to give pooled estimates of the effect of EGFR‐TKI therapy on objective response rate (ORR), one‐year progression‐free survival (PFS), and two‐year overall survival (OS).ResultsWe identified 13 eligible trials involving 912 patients. Prospective meta‐analysis demonstrated that the ORR of the 19 deletion group was significantly higher than the 21 L858R mutation group (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.18–3.33; P = 0.01), but no statistical significance between the one‐year PFS rate of the 19 deletion and 21 L858R groups (OR 1.44, 95% CI 0.96–2.18; P = 0.08) was found. However, retrospective meta‐analysis demonstrated that a significantly higher one‐year PFS rate was associated with the 19 deletion group (OR 1.73, 95% CI 1.17–2.56; P = 0.006). The two‐year survival rate of the 19 deletion group was significantly higher than the 21 L858R group (OR 5.27, 95 % CI 1.76–15.71; P = 0.003).ConclusionsIn advanced NSCLC patients, an exon 19 deleton may provide superior ORR, PFS, and OS after EGFR‐TKI treatment compared with an exon 21 L858R mutation.
Resistance to Tomato leaf curl New Delhi virus in Cucurbita spp.
Authors: Sáez C. , Martínez C. , Ferriol M. , Manzano S. , Velasco L. , Jamilena M. , López C. , Picó B. 
Published: March 2016

AbstractTomato leaf curl New Delhi virus (ToLCNDV) is a bipartite begomovirus (family Geminiviridae) first reported in India and its neighbouring countries. ToLCNDV severely affects zucchini crop (Cucurbita pepo) in the main production areas of Southern Spain since 2012. This emerging begomovirus is a serious threat to this and other cucurbit crops. Breeding resistant cultivars is the most promising method for disease control, but requires the identification of sources of resistance in the Cucurbita genus. In this work, we screened for ToLCNDV resistance a large collection of Cucurbita spp. accessions, including landraces and commercial cultivars of the main cultivated species, C. pepo, Cucurbita moschata and Cucurbita maxima and wild species. The screening was performed using mechanical and whitefly inoculation. The level of resistance was assessed by scoring symptom severity and by measuring the virus content with quantitative polymerase chain reaction in selected genotypes. Diversity in the response was observed within and among species. Severe symptoms and high viral amounts were found at 30 days after mechanical and whitefly inoculation in C. pepo, in all accessions belonging to the Zucchini morphotype and to other morphotypes of both subspecies, pepo and ovifera, and even in the wild relative Cucurbita fraterna. C. maxima was also highly susceptible. This species showed characteristic symptoms of leaf decay and intense yellowing, different from those of mosaic, curling and internode shortening found in C. pepo. The only species showing resistance was C. moschata. Four accessions were symptomless or had some plants with only mild symptoms after three independent rounds of mechanical inoculation with different inoculum sources. Two of them also remained symptomless after virus inoculation with viruliferous whiteflies. ToLCNDV was detected in these asymptomatic accessions at 15 and 30 days post inoculation, but viral amounts were much lower than those found in susceptible genotypes, suggesting a high level of resistance. The symptoms in the susceptible accessions of this species were also different, with a characteristic leaf mottling, evolving to a severe mosaic. The newly identified C. moschata resistant accessions are good candidates for breeding programmes to avoid the damage caused by ToLCNDV.
Baseline medical comorbidities in adults randomized in the STRIDE trial for psychostimulant use disorders
Authors: dela Cruz Adriane M. , Carmody Thomas , Greer Tracy L. , Rethorst Chad D. , Warden Diane , Walker Robrina , Trivedi Madhukar H. 
Published: March 2016

Background and ObjectivesRates of medical illnesses may be higher among individuals with substance use disorders, complicating their care. This study aimed to expand the understanding of other medical conditions in treatment‐seeking adults with stimulant use disorder (SUD) using data from Stimulant Reduction Intervention using Dose Exercise (STRIDE), a randomized, multisite trial investigating exercise augmentation of treatment as usual.MethodsUtilizing STRIDE baseline data, we examined demographic and clinical characteristics based on the number of self‐reported diagnosed medical conditions among participants meeting eligibility criteria (passing medical screening exam and maximal exercise test, non‐opioid dependent, no concomitant beta blocker, or opioid replacement therapy).ResultsThe majority (59%) of study participants (N = 302, mean age all participants = 39 years) did not report any history of other medical problems. Those with two or more conditions were older (mean age 46 years), reported more pain and worse physical functioning, and more psychiatric disorders (average 1.44). Hypertension was more common among participants with cocaine use disorders only (present in 16%) and liver disease was more common in those with cocaine plus other stimulant use disorders (present in 7%).Conclusion and Scientific SignificanceIn this sample, patients with SUD were in surprisingly good health. A subpopulation had an overall higher burden of illness with worsened physical and psychiatric functioning. Provision of coordinated care may optimize treatment outcomes for patients based on medical comorbidity burden as well as type of drug abused, although these conclusions should be considered preliminary as they are based on self‐reported data. (Am J Addict 2016;25:215–220)
An independent replication of the Adolescent‐Community Reinforcement Approach with justice‐involved youth
Authors: Henderson Craig E. , Wevodau Amy L. , Henderson Susan E. , Colbourn Scholar L. , Gharagozloo Laadan , North Lindsey W. , Lotts Vivian A. 
Published: March 2016

Background and ObjectivesSubstance use disorders among youth remain a serious public health problem. Although research has overwhelmingly supported the use of evidenced‐based interventions, one of the primary limitations of the current evidence base is that for the vast majority of treatments, the developers of the treatments are also the ones conducting research on them, raising the possibility of allegiance bias.MethodsThe present study was an independently conducted randomized controlled trial (n = 126) comparing an evidenced‐based treatment for adolescent substance use, Adolescent‐Community Reinforcement Approach (A‐CRA), and assertive continuing care (ACC), to services as usual (SAU) provided by a juvenile probation department. Latent growth curve modeling was used to compare the treatments on change in substance use assessed by the Global Appraisal of Individual Needs (GAIN) at baseline and 3, 6, and 12 months following treatment entry.ResultsAll youth evidenced a substantial reduction in substance use frequency and substance‐related problems following treatment; however, youth treated with A‐CRA/ACC evidenced a substantially greater decrease in substance‐related problems.Conclusions and Scientific SignificanceResults are consistent with studies conducted by A‐CRA/ACC model developers supporting the effectiveness of the clinical approach and, because the outcomes resulted from an independent replication, are encouraging for the transportation potential of A‐CRA/ACC. (Am J Addict 2016;25:233–240)
Effects of an Enhanced Recovery After Surgery programme on emergency surgical patients
Authors: Wisely Jessica C. , Barclay Karen L. 
Published: March 2016

BackgroundEnhanced Recovery After Surgery (ERAS) programmes have been used in elective surgery since the 1990s to optimize peri‐operative care, reducing post‐operative complications, length of stay and overall costs. Following the local introduction of an ERAS programme for colorectal elective patients, it was suggested an increase in the use of ERAS‐type principles in emergency patients may have occurred. The aims of this study were to determine whether management changes could be demonstrated and if there was a difference in outcomes.MethodA retrospective cohort study comparing emergency patients undergoing major abdominal surgery October 2008 to May 2010 (pre‐ERAS) and January 2011 to December 2012 (post‐ERAS) was performed. Details collected included admission and operative details, post‐operative management and outcomes.ResultsA total of 370 patients were studied. Baseline variables were comparable. Post‐ERAS, intra‐operative (P < 0.001) and post‐operative 48 h totals (P < 0.001) of intravenous fluids were significantly reduced. Significantly fewer patients in the post‐ERAS group had a catheter (P < 0.001), drain (P = 0.001) and patient controlled analgesia (P = 0.01) for more than 2 days. Major complications (P = 0.002) and individual minor complications such as urinary tract infections (P = 0.02), urinary retention (P = 0.001) and chest infections (P = 0.001) were all significantly reduced in the post‐ERAS period.ConclusionThis study demonstrates a significant change in management towards ERAS principles in emergency patients following the introduction of such a programme in elective patients. The lack of increased complications in the second period suggests the use of ERAS principles is not harmful. The wider application of ERAS principles could improve outcomes in emergency surgery and deserves further study.
A real‐world study focused on the long‐term efficacy of mycophenolate mofetil as first‐line treatment of autoimmune hepatitis
Authors: Zachou K. , Gatselis N. K. , Arvaniti P. , Gabeta S. , Rigopoulou E. I. , Koukoulis G. K. , Dalekos G. N. 
Published: March 2016

SummaryBackgroundFront‐line therapy with mycophenolate mofetil (MMF) in autoimmune hepatitis (AIH) has shown high on‐treatment remission rates.AimTo study prospectively in a real‐world fashion the long‐term outcome of a large group of consecutive treatment‐naïve AIH patients.MethodsBetween 2000 and 2014, 158 patients were recruited but only 131 were eligible for treatment (109 MMF/prednisolone; 22 prednisolone ± azathioprine). Long‐term data on outcome after drug withdrawal were evaluated. Patients stopped treatment after having achieved complete response (normal transaminases and IgG) for at least the last 2 years.ResultsAt diagnosis, 31.6% of patients had cirrhosis and 72.8% insidious presentation. A total of 102 of 109 (93.6%) responded initially to MMF within 2 (1–18) months. A total of 78 of 109 (71.6%) had complete response on treatment and 61 of 78 (78.2%) maintained remission off prednisolone. MMF‐treated patients had increased probability of complete response compared to those receiving azathioprine (P = 0.03). Independent predictors of complete response were lower ALT at 6 months (P = 0.001) and acute presentation (P = 0.03). So far, treatment withdrawal was feasible in 40/109 patients and 30 (75%) are still in remission after 24 (2–129) months. Remission maintenance was associated with longer MMF treatment (P = 0.005), higher baseline ALT (P < 0.02), lower IgG on 6 months (P = 0.004) and histological improvement.ConclusionsMycophenolate mofetil proved to be an efficient first‐line treatment for AIH, achieving so far the highest rates of remission maintenance off treatment (75%) ever published for at least a median of 2 years, although the remission criteria used were strict. However, the risk of potential bias and overestimation of intervention benefits from MMF cannot be completely excluded as this is a real world and not a randomised controlled trial.
Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype
Authors: Kagami T. , Sahara S. , Ichikawa H. , Uotani T. , Yamade M. , Sugimoto M. , Hamaya Y. , Iwaizumi M. , Osawa S. , Sugimoto K. , Miyajima H. , Furuta T. 
Published: March 2016

SummaryBackgroundAcid inhibitory effects of proton pump inhibitors (PPIs) are influenced by CYP2C19 genotype. In contrast, the potent acid inhibition of vonoprazan is not influenced by CYP2C19 genotype.AimTo compare the acid inhibitory effects of vonoprazan and esomeprazole in relation to CYP2C19 genotype.MethodsTwenty‐eight healthy Japanese volunteers [7 CYP2C19 poor metabolisers (PMs), 11 intermediate metabolisers (IMs) and 10 rapid metabolisers (RMs)] received four different regimens in a randomised crossover manner: (i) vonoprazan 20 mg twice daily (b.d.), (ii) vonoprazan 20 mg daily, (iii) esomeprazole 20 mg b.d. and (iv) esomeprazole 20 mg daily. The timing of each dosing was 1 h before a meal. Twenty‐four‐hour intragastric pH monitoring was performed on day 7 on each regimen.ResultsIn the overall genotype group, pH ≥4 holding time ratios (pH 4 HTRs) with vonoprazan b.d., vonoprazan daily, esomeprazole b.d. and esomeprazole daily were 100%, 95%, 91%, and 68% respectively. pH 5 HTRs were 99%, 91%, 84% and 54% respectively. Vonoprazan b.d. potently suppressed acid for 24 h, and was significantly superior to other regimens irrespective of CYP2C19 genotype. Vonoprazan daily was equivalent to esomeprazole b.d. in IMs and PMs, but superior in RMs. CYP2C19 genotype‐dependent differences were observed in esomeprazole daily but not in vonoprazan b.d. or daily.ConclusionVonoprazan 20 mg b.d. inhibits acid irrespective of CYP2C19 genotype, more potently than esomeprazole 20 mg b.d., pH 4 and 5 holding time ratios reached 100% and 99%, respectively.
The effect of colostrum ingestion during the first 24 hours of life on early postnatal development of piglet immune systems
Authors: Ogawa Shohei , Tsukahara Takamitsu , Imaoka Taishi , Nakanishi Nobuo , Ushida Kazunari , Inoue Ryo 
Published: March 2016

AbstractIt has been suggested that colostrum is important not only for direct protection from pathogens but also for proper development of immune systems in piglets. In this study, we focused on the effect of colostrum ingestion during the first 24 h of life on early postnatal development of piglet immune systems. Thirty‐six piglets from five litters were divided into colostrum‐fed (CoF) and colostrum‐deprived (CoD) groups. The former group was allowed to suckle normally while formula milk was fed to the latter group during the first 24 h of life. At the weaning period, the concentrations of fecal immunoglobulin (Ig) A and plasma IgG as well as the number of blood leukocyte subsets were analyzed. Fecal IgA and plasma IgG concentrations in the CoF group were more than twice as high as those in the CoD group (P < 0.01). In addition, the number of blood B cells was significantly higher in the CoF group than that in the CoD group (P < 0.05). This study demonstrates that colostrum ingestion during the first 24 h plays a significant role in early postnatal development of both mucosal and systemic immunity of piglets.
Effect of linseed oil supplementation on performance and milk fatty acid composition in dairy cows
Authors: Suksombat Wisitiporn , Thanh Lam Phuoc , Meeprom Chayapol , Mirattanaphrai Rattakorn 
Published: March 2016

AbstractThirty‐six Holstein‐Friesian crossbred lactating dairy cows were used to determine the effects of linseed oil supplementation on performance and milk fatty acid (FA) profile. Three treatments were as follows: basal diet (56:44 Roughage:concentrate [R:C] ratio, dry matter basis) supplemented with 500 g of palm oil as control (PO), 500 g mixture (1:1, w/w) of palm oil and linseed oil (POLSO) and 500 g of linseed oil (LSO). The LSO supplementation had no effects on total dry matter intake (DMI), milk yield and milk composition. Compared to control cows, cows supplemented with LSO increased milk concentrations of cis‐9,trans‐11 conjugated linoleic acid (CLA) and n‐3 FA (P < 0.05), particularly C18:3n‐3, C20:5n‐3 and C22:6n‐3. Feeding LSO reduced concentrations of milk short‐ and medium‐chain saturated fatty acids (P < 0.05) while it increased concentration of milk unsaturated fatty acids (P < 0.05). Milk proportions of n‐3 FA increased, whereas n‐6/n‐3 ratio decreased in the LSO as compared with the control (P < 0.05). In conclusion, supplementing dairy cows' diet based on corn silage with LSO at 500 g/day could improve the nutritional value of milk with potential health‐beneficial FA without detrimental effect on milk composition or cow's performance.
Tirapazamine has no Effect on Hepatotoxicity of Cisplatin and 5‐fluorouracil but Interacts with Doxorubicin Leading to Side Changes in Redox Equilibrium
Authors: Mandziuk Slawomir , Matysiak Wlodzimierz , Korga Agnieszka , Burdan Franciszek , Pasnik Iwona , Hejna Marcin , Korobowicz‐Markiewicz Agnieszka , Grzycka‐Kowalczyk Luiza , Kowalczyk Michal , Poleszak Ewa , Jodlowska‐Jedrych Barbara , Dudka Jaroslaw 
Published: March 2016

AbstractTirapazamine is a hypoxia‐activated prodrug which was shown to exhibit up to 300 times greater cytotoxicity under anoxic in comparison with aerobic conditions. Thus, the combined anticancer therapy of tirapazamine with a routinely used anticancer drug seems to be a promising solution. Because tirapazamine undergoes redox cycle transformation in this study, the effect of tirapazamine on redox hepatic equilibrium, lipid status and liver morphology was evaluated in rats exposed to cisplatin, doxorubicin and 5‐fluorouracil. Rats were intraperitoneally injected with tirapazamine and a particular cytostatic. The animals were killed, and blood and liver were collected. Hepatic glucose, total cholesterol, triglycerides, NADH, NADPH glutathione and the activity of glucose‐6‐phosphate dehydrogenase were determined. Liver morphology and the immune expression of HMG‐CoA‐reductase were also assessed. Glucose, total cholesterol, triglycerides, bilirubin concentrations and the activity of aspartate and alanine aminotransferases were determined in the plasma. Tirapazamine displayed insignificant interactions with cisplatin and 5‐fluorouracil referring to hepatic morphology and biochemical parameters. However, tirapazamine interacts with doxorubicin, thus leading to side changes in redox equilibrium and lipid peroxidation, but those effects are not severe enough to exclude that drug combination from further studies. Thus, tirapazamine seems to be a promising agent in successive studies on anticancer activity in similar schedules.
Development of stratum corneum chymotrypsin-like protease activity and natural moisturizing factors from birth to 4 weeks of age compared with adults
Authors: Chittock J. , Cooke A. , Lavender T. , Brown K. , Wigley A. , Victor S. , Cork M.J. , Danby S.G. 
Published: March 2016

Summary

Background
From birth, the functional properties of the neonatal epidermal barrier mature whereby the stratum corneum (SC) hydrates and the skin surface acidifies. The identification of a thinner infant SC compared with adults suggests underdeveloped mechanisms underlying differentiation and desquamation.

Objectives
To assess the functional properties of the neonatal SC from birth, in conjunction with the quantification of superficial chymotrypsin-like protease activity [kallikrein-7 (KLK-7)] and filaggrin-derived natural moisturizing factors (NMF).

Methods
A total of 115 neonates recruited to the Oil in Baby SkincaRE (OBSeRvE) randomized controlled trial underwent a full evaluation of the SC at birth (&lt; 72 h old) and at 4 weeks of age (n = 39, no oil control group) using minimally invasive instrumentation and methodology. A cohort of 20 unrelated adults was recruited for comparison.

Results
At birth NMF levels correlated with SC hydration (r = 0·50) and skin-surface pH (r = −0·54). From birth to 4 weeks, transepidermal water loss (TEWL), superficial KLK-7 activity and filaggrin-derived NMF significantly elevated. Impaired epidermal barrier function at birth (&gt; 75th percentile TEWL) was accompanied by significantly elevated chymotrypsin-like protease activity and reduced levels of NMF.

Conclusions
The biophysical, biological and functional properties of the developing neonatal SC are transitional from birth to 4 weeks of age and differ significantly from adults. The presence of impaired barrier function with elevated protease activity and reduced NMF at birth suggests why certain infants are predisposed to epidermal barrier breakdown and the development of atopic dermatitis.
Mobile technologies for learning: Exploring critical mobile learning literacies as enabler of graduateness in a South African research‐led University
Authors: Bosman J. P. , Strydom Sonja 
Published: March 2016

AbstractAt Stellenbosch University there is a drive to integrate the development of graduate attributes and the use of emerging technologies in the curriculum. With the aim of discovering the role of emerging mobile technologies in learning a qualitative research project was undertaken with a senior‐student cohort. An inductive thematic analysis was done using Ng's () mLearning literacies framework (cognitive, socio‐emotional and technical), and situating it within the field of graduateness (Barrie ; Bozalek & Watters, ). This paper reports on the research which informs the literature on graduateness with regards to the potential role of critical mobile learning literacies and expands the application of the mLearning literacies framework as part of the digital literacies debate. Resulting themes were: (1) a critical awareness of 21st century learning; (2) an underdeveloped mLearning literacy (with criticality as indicator); and (3) multidimensional expectations regarding the development of mLearning literacy. To support the notion of lifelong learning and graduateness, we call for the development of particularly criticality in mLearning literacy skills at a cognitive, socio‐emotional and technical level with mobile devices in both formal and informal learning. This has implications for curriculum design, pedagogic approaches and a focus on interactions with new forms of knowledge.