bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homologous role of CovRS two‐component regulatory system in NAD+‐glycohydrolase activity in Streptococcus dysgalactiae subsp. equisimilis as in Streptococcus pyogenes
Authors: Hasegawa Tadao , Matsumoto Masakado , Hata Nanako , Yano Hisako , Isaka Masanori , Tatsuno Ichiro 
Published: January 2019

Streptococcal toxic shock syndrome (STSS) is primarily caused by Streptococcus pyogenes, but it may also be caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE). The analyses of S. pyogenes have revealed the important roles of NAD+‐glycohydrolase (Nga) and CovR/CovS, a two‐component regulatory system. We examined these factors in SDSE by analyzing mainly two isogenic SDSE strains (12‐10‐1 and 12‐10‐3) from the blood of a patient with STSS. The Nga activities were measured and the nucleotide sequences of covR and covS genes were determined. We detected one nucleotide difference between the covR gene of 12‐10‐1 and that of 12‐10‐3, and the Nga activity of 12‐10‐1 was approximately 6.8‐fold more than that of 12‐10‐3. The introduction of covR of 12‐10‐3 into 12‐10‐1 significantly reduced the Nga activity, but the introduction of 12‐10‐1 covR into itself had only a little effect. In addition, the knockout of covR or covS of 12‐10‐3 remarkably increased the Nga activity. We are the first to report that strains with wild‐type and mutated covR were isolated simultaneously from an SDSE STSS patient and that the CovR/CovS two‐component regulatory system is involved in the Nga activity in SDSE as well as in S. pyogenes.
Carbamoyl phosphate synthetase 1 (CPS1) as a prognostic marker in chronic hepatitis C infection
Authors: El‐Sheikh Ranya M. , Mansy Soheir S. , Nessim Iris G. , Hosni Hala N. , El Hindawi Ali , Hassanein Moataz H. , AbdelFattah Ahmed S. 
Published: January 2019

This study aims to assess the value of carbamoyl phosphate synthetase 1 (CPS1), as a non‐invasive serum marker, for the evolution of chronic HCV infection and hepatic fibrosis. Seventy‐two patients with HCV positive serum RNA and 15 health volunteers were enrolled in this study. Out of 72 patients, 10 patients had decompensated liver with ascites. Quantitative analysis of CPS1 was performed in the harvested sera and corresponding liver biopsies using ELISA and immunohistochemistry techniques respectively. Also, mitochondrial count using electron microscopy, urea analysis and conventional liver tests were done. Patients were grouped into (F1 + F2) and (F3 + F4) representing stages of moderate and severe fibrosis respectively. Tissue and serum CPS1 (s.CPS1) correlated significantly in moderate and severe fibrosis. Patients with severe fibrosis showed significantly higher levels of s.CPS1 (p‐value ≤ 0.05) and significantly lower mitochondrial counts (p‐value = 0.0065) than those with moderate fibrosis. S.urea positively correlated with s.CPS1 only in the decompensated group, at which s.urea reached maximal levels. In conclusion, s.CPS1 is a potential non‐invasive marker for the assessment of severity and progression of HCV in relation to mitochondrial dysfunction. Also, increased s.urea with the progression of the disease is mainly due to a concurrent renal malfunction, which needs further investigation.
Systematic review with meta‐analysis: the critical role of dermatological events in patients with hepatocellular carcinoma treated with sorafenib
Authors: Díaz‐González Álvaro , Sanduzzi‐Zamparelli Marco , Sapena Víctor , Torres Ferran , LLarch Neus , Iserte Gemma , Forner Alejandro , da Fonseca Leonardo , Ríos José , Bruix Jordi , Reig María 
Published: January 2019

SummaryBackgroundThe positive results of the REFLECT trial in terms of survival (sorafenib vs lenvatinib) offer a new first‐line option for hepatocellular carcinoma. Additionally, the expected results of immunotherapy could change the first‐line treatment in hepatocellular carcinoma or the clinical trial design in first and second‐line.AimsTo evaluate the impact of dermatologic adverse events under sorafenib in hepatocellular carcinoma patients as a clinical marker to predict prognosis and critically evaluate outcomes within trials.MethodsA systematic search of original articles published until October 2018 was performed using PubMed/MEDLINE and a meta‐analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement.ResultsA total of 393 studies were identified and 13 articles with 2035 patients (79.5% Child‐Pugh‐A, 73.2% BCLC‐C) were selected for qualitative and quantitative analysis. The main type of dermatologic adverse events was hand‐foot skin reaction (47.7%) but other dermatologic adverse events were reported in 31.7% of the cases. Presence of dermatologic adverse events was associated with a lower mortality when compared with those patients without them (pooled Hazard Ratio for the univariate analysis 0.45 (95% CI: 0.38‐0.53) and there was no heterogeneity for the analysis (P = 0.511; I2 = 0.0%). Refuting this association would require the future report of 1370 negative studies.ConclusionsThis meta‐analysis shows a clinically meaningful association between dermatologic adverse events and a higher probability of longer survival. These data support the use of dermatologic adverse events in the clinical decision‐making when informing the prognosis and when systemic treatment is decided.
Vocabulary Development and Trajectories of Behavioral and Emotional Difficulties Via Academic Ability and Peer Problems
Authors: Westrupp Elizabeth M. , Reilly Sheena , McKean Cristina , Law James , Mensah Fiona , Nicholson Jan M. 
Published: January 2019

This study investigates associations between trajectories of children's vocabulary development and subsequent behavioral and emotional difficulties via two potential mediating mechanisms; literacy and peer problems. Nationally representative data from 4,983 Australian children were used to examine trajectories of receptive vocabulary (4–5, 6–7, and 8–9 years) and hyperactivity‐inattention, conduct problems and emotional symptoms (8–9, 10–11, 12–13, 14–15 years), and literacy and peer problems (8–9 years). Lower growth in vocabulary was related to trajectories of hyperactivity‐inattention, conduct problems, and emotional symptoms. Literacy was a key mediator explaining these associations. Results were consistent for children below the 50th percentile for vocabulary at 4–5 years compared to the full sample. These findings suggest that early literacy‐based interventions may alleviate declining academic, emotional and behavioral functioning in adolescence.
The Capricious Nature of Theory of Mind: Does Mental State Understanding Depend on the Characteristics of the Target?
Authors: Gönültaş Seçil , Selçuk Bilge , Slaughter Virginia , Hunter John A. , Ruffman Ted 
Published: January 2019

Using a between‐groups design and random assignment, this study examined 214 Turkish children's (M = 11.66 years) mindreading and general reasoning about in‐group members (Turks), similar out‐group members (Syrians within Turkey) and dissimilar out‐group members (Northern Europeans). Children heard four mindreading and four general reasoning stories with in‐group or out‐group members as targets. Whereas children's general reasoning about three groups was equivalent, accuracy of mental state inferences differed by target with more accurate mindreading of in‐group targets compared to both sets of out‐group targets. In this Turkish sample, mindreading of Syrian targets was the least accurate. Prejudice and perceived realistic threat predicted lower mindreading. These findings have important implications for understanding how similarity and intergroup processes play a role in children's mindreading.
Genome‐wide association study of inhaled corticosteroid response in admixed children with asthma
Authors: Hernandez‐Pacheco Natalia , Farzan Niloufar , Francis Ben , Karimi Leila , Repnik Katja , Vijverberg Susanne J. , Soares Patricia , Schieck Maximilian , Gorenjak Mario , Forno Erick , Eng Celeste , Oh Sam S. , Pérez‐Méndez Lina , Berce Vojko , Tavendale Roger , Samedy Lesly‐Anne , Hunstman Scott , Hu Donglei , Meade Kelley , Farber Harold J. , Avila Pedro C. , Serebrisky Denise , Thyne Shannon M. , Brigino‐Buenaventura Emerita , Rodriguez‐Cintron William , Sen Saunak , Kumar Rajesh , Lenoir Michael , Rodriguez‐Santana Jose R. , Celedón Juan C. , Mukhopadhyay Somnath , Potočnik Uroš , Pirmohamed Munir , Verhamme Katia M. , Kabesch Michael , Palmer Colin N. A. , Hawcutt Daniel B. , Flores Carlos , Maitland‐van der Zee Anke H. , Burchard Esteban G. , Pino‐Yanes Maria 
Published: January 2019

SummaryBackgroundInhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome‐wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response.ObjectiveWe aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings.MethodsA meta‐analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10−6 were followed up for replication in 1697 asthmatic patients from six European studies. Associations of ICS response described in published GWAS were followed up for replication in the admixed populations.ResultsA total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10−6). One of them, located in the intergenic region of APOBEC3B and APOBEC3C, showed evidence of replication in Europeans (rs5995653, P = 7.52 × 10−3) and was also associated with change in lung function after treatment with ICS (P = 4.91 × 10−3). Additionally, the reported association of the L3MBTL4‐ARHGAP28 genomic region was confirmed in admixed populations, although a different variant was identified.Conclusions and clinical relevanceThis study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment.
Morbidity related to diverting ileostomy after restorative proctocolectomy in patients with ulcerative colitis
Authors: Karjalainen E. K. , Renkonen‐Sinisalo L. , Mustonen H. K. , Lepistö A. H. 
Published: January 2019

AbstractAimRestorative proctocolectomy with ileal pouch–anal anastomosis is considered by many surgeons to be the standard procedure for surgical management of ulcerative colitis. There is controversy about whether or not a covering ileostomy should be constructed. The aim of this study was to evaluate the outcomes and morbidity for patients with ulcerative colitis who underwent restorative proctocolectomy with or without a diverting ileostomy.MethodThis is a retrospective study of a consecutive series of 510 patients with ulcerative colitis who were operated on in Helsinki University Hospital between January 2005 and June 2016. A diverting ileostomy was performed in 119 patients (the stoma group) compared with 391 patients with no stoma.ResultsDehydration and intestinal obstruction occurred more often in the stoma group (P < 0.0001). Clinical anastomotic leakage was more common among patients without an ileostomy (6.6% vs 1.7%, P = 0.04). However, the need for re‐laparotomy because of any early complication did not differ between the groups (P = 0.58). Within 3 months, 50 patients with ileostomy (42.0%) and 51 patients without (13.0%) were readmitted (P < 0.0001). In total, 35 patients (29.3%) had a complication relating to ileostomy closure and four of them required surgery. There was no difference in the rate of fistulas, pouchitis or pouch failure between the groups.ConclusionOur study shows that a diverting ileostomy is associated with considerable morbidity but it does not seem to prevent later failure of the pouch. We suggest that a diverting ileostomy should only be constructed for high‐risk patients.
The evolving risk of sudden cardiac death after heart transplant. An analysis of the ISHLT Thoracic Transplant Registry
Authors: Alba Ana C. , Fan Chun‐Po S. , Manlhiot Cedric , Dipchand Anne I. , Stehlik Josef , Ross Heather J. 
Published: January 2019

AbstractSudden cardiac death (SCD) is responsible for ~10% of post‐heart transplant deaths. We conducted a retrospective analysis of the ISHLT registry evaluating the risk of post‐transplant SCD. Adult heart transplant recipients (2004‐2014) surviving the first year were included. We used multivariable multistate competing risk survival analysis to evaluate the impact of history of treated rejection and cardiac allograft vasculopathy (CAV) on SCD risk. We used a probabilistic analytical model and Monte Carlo simulation to estimate the impact of CAV severity and graft dysfunction on SCD. We included 25 242 recipients. During a median follow‐up of 4.7 (2.3‐7.0) years, 582 patients died suddenly. Treated rejection (HR 1.76, 95% CI 1.36‐2.31) and CAV (HR 3.32, 95% CI 2.73‐4.03) were important risk factors for SCD. The estimated SCD risk in patients with severe CAV without and with graft dysfunction was 3.2% (95% CI 2.0‐4.6) and 5.4% (95% CI 3.8‐7.0), respectively, at 2 years from the CAV diagnosis, and 4.9% (95% CI 3.4‐6.5) and 8.0% (95% CI 6.1‐10.0), respectively, in those who also had treated rejection. These results provide evidence that recipients with severe CAV and graft dysfunction or treated rejection are at clinically significant increased SCD risk. The benefit of ICD post‐transplant remains uncertain.
Spatially explicit species distribution models: A missed opportunity in conservation planning?
Authors: Domisch Sami , Friedrichs Martin , Hein Thomas , Borgwardt Florian , Wetzig Annett , Jähnig Sonja C. , Langhans Simone D. 
Published: January 2019

AbstractAimSystematic conservation planning is vital for allocating protected areas given the spatial distribution of conservation features, such as species. Due to incomplete species inventories, species distribution models (SDMs) are often used for predicting species’ habitat suitability and species’ probability of occurrence. Currently, SDMs mostly ignore spatial dependencies in species and predictor data. Here, we provide a comparative evaluation of how accounting for spatial dependencies, that is, autocorrelation, affects the delineation of optimized protected areas.LocationSoutheast Australia, Southeast U.S. Continental Shelf, Danube River Basin.MethodsWe employ Bayesian spatially explicit and non‐spatial SDMs for terrestrial, marine and freshwater species, using realm‐specific planning unit shapes (grid, hexagon and subcatchment, respectively). We then apply the softwaregurobito optimize conservation plans based on species targets derived from spatial and non‐spatial SDMs (10%–50% each to analyse sensitivity), and compare the delineation of the plans.ResultsAcross realms and irrespective of the planning unit shape, spatially explicit SDMs (a) produce on average more accurate predictions in terms of AUC, TSS, sensitivity and specificity, along with a higher species detection probability. All spatial optimizations meet the species conservation targets. Spatial conservation plans that use predictions from spatially explicit SDMs (b) are spatially substantially different compared to those that use non‐spatial SDM predictions, but (c) encompass a similar amount of planning units. The overlap in the selection of planning units is smallest for conservation plans based on the lowest targets and vice versa.Main conclusionsSpecies distribution models are core tools in conservation planning. Not surprisingly, accounting for the spatial characteristics in SDMs has drastic impacts on the delineation of optimized conservation plans. We therefore encourage practitioners to consider spatial dependencies in conservation features to improve the spatial representation of future protected areas.
Higher rates of large‐for‐gestational‐age newborns mediated by excess maternal weight gain in pregnancies with Type 1 diabetes and use of continuous subcutaneous insulin infusion vs multiple dose insulin injection
Authors: Hauffe F. , Schaefer‐Graf U. M. , Fauzan R. , Schohe A. L. , Scholle D. , Sedlacek L. , Scherer K. A. , Klapp C. , Ramsauer B. , Henrich W. , Schlembach D. , Abou‐Dakn M. 
Published: January 2019

AbstractAimsTo compare glycaemic control, maternal and neonatal outcomes in pregnancies with Type 1 diabetes, managed either by continuous subcutaneous insulin infusion, multiple daily insulin injection or switch from multiple daily insulin injection (MDI) to continuous subcutaneous insulin infusion (CSII) in early pregnancy.Research design and methodsData from 339 singleton pregnancies were retrospectively reviewed. HbA1c values were measured preconception and in each trimester. In a secondary analysis, use of CSII pre‐pregnancy was compared with initiation of CSII during pregnancy.ResultsMDI was used in 140 pregnancies (41.3%) and CSII was used in 199 (58.7%), including 34 pregnancies (10.0%) during which the women switched to CSII. In pregnancies during which CSII was used duration of diabetes [median (interquartile range) 16.0 (8.0–23.0) years vs 11.0 (5.5–17.5) years; P<0.001] was longer, and the Institute of Medicine recommendations for appropriate weight gain were exceeded more often (64.8% vs. 50.8%; P=0.01). CSII use and pre‐pregnancy BMI were independent predictors of excess weight gain. There was no difference in glucose control, but CSII was associated with higher birth weight [median (interquartile range) 3720 (3365–4100) g vs 3360 (3365–4100) g; P<0.001] and higher large‐for‐gestational‐age (LGA) rate (44.7% vs. 33.6%; P=0.04) than MDI. HbA1c concentration in the third trimester and excess weight gain were predictive of LGA infants [odds ratio 2.33 (95% CI 1.54–3.51); P<0.001 and 1.89 (95% CI 1.02–3.51); P=0.04]. In pregnancies where CSII therapy was initiated in the first trimester and in those with pre‐pregnancy use, similar glucose control and outcome was achieved.ConclusionsThere was no advantage of CSII with respect to glycaemic control and neonatal outcomes. The rate of LGA neonates was higher in the CSII group, possibly mediated by excess maternal weight gain, which was more frequent than in women treated with MDI.
How tightly controlled do fluctuations in blood glucose levels need to be to reduce the risk of developing complications in people with Type 1 diabetes?
Authors: Livingstone R. , Boyle J. G. , Petrie J. R. 
Published: January 2019

AbstractIn 2011, the James Lind Alliance published a ‘top 10’ list of priorities for Type 1 diabetes research based on a structured consultation process. Whether reducing fluctuations in blood glucose can prevent long‐term microvascular and macrovascular complications was one of these. In this narrative review, 8 years on, we have assessed the updated evidence for the assertion that increased glucose variability plays an independent and clinically important role in the complications of Type 1 diabetes, over and above mean blood glucose and the effects of hypoglycaemia: the ‘glucose variability hypothesis’. Although studies in cultured cells and ex vivo vessels have been suggestive, most studies in Type 1 diabetes have been small and/or cross‐sectional, and based on ‘finger‐prick’ glucose measurements that capture glucose variability only in waking hours and are affected by missing data. A recent analysis of the Diabetes Control and Complications Trial that formally imputed missing data found no independent effect of short‐term glucose variability on long‐term complications. Few other high‐quality longitudinal studies have directly addressed the glucose variability hypothesis in Type 1 diabetes. We conclude that there is little substantial evidence to date to support this hypothesis in Type 1 diabetes, although increasing use of continuous glucose monitoring provides an opportunity to test it more definitively. In the meantime, we recommend that control of glycaemia in Type 1 diabetes should continue to focus on the sustained achievement of target HbA1c and avoidance of hypoglycaemia.
Sodium‐glucose co‐transporter‐2 inhibitor use and risk of lower‐extremity amputation: Evolving questions, evolving answers
Authors: Yang Jeff Y. , Wang Tiansheng , Pate Virginia , Gower Emily W. , Crowley Matthew J. , Buse John B. , Stürmer Til 
Published: January 2019

AimTo examine whether sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors are associated with a higher risk of lower‐extremity amputation than dipeptidyl‐peptidase‐4 (DPP‐4) inhibitors and sulphonylureas.MethodsWe conducted a retrospective cohort study, using the MarketScan Commercial Claims and Encounters Database (2013‐2015), to compare the incidence of lower‐extremity amputation (LEA) between initiators of SGLT2 inhibitors and initiators of two second‐line drugs, DPP‐4 inhibitors and sulphonylureas (SUs). We estimated crude incidence rates (IRs) and adjusted hazard ratios (aHR), with 95% confidence intervals (CIs), before and after propensity‐score weighting. We additionally conducted sensitivity analyses using a comparator group of all non‐metformin, non‐SGLT2 inhibitor glucose‐lowering drugs, as previous studies used this approach.ResultsIn a cohort of 328 150 individuals aged 18 to 64 years, the IR of LEA ranged from 1.5 to 2.4 per 1000 person‐years. In as‐treated analysis, the estimated hazard of LEA was increased among SGLT2 inhibitor initiators compared to DPP‐4 inhibitor initiators (aHR 1.69, 95% CI 1.20‐2.38), but not compared to SU initiators (aHR 1.02, 95% CI 0.67‐1.55) or non‐metformin, non‐SGLT2 inhibitor initiators (aHR 1.02, 95% CI 0.54‐1.93). Results were consistent in intention‐to‐treat analysis and across a number of sensitivity analyses.ConclusionsAmong commercially insured patients in the United States, our results suggest that initiation of SGLT2 inhibitors may increase the risk of LEA compared to initiation of DPP‐4 inhibitors. Contrasting results when comparing SGLT2 inhibitor initiators to DPP‐4 inhibitor and SU initiators highlight the importance of choosing appropriate comparator drugs when addressing comparative effectiveness and safety questions that can inform clinical decision‐making.