bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiles of recovery from alcohol use disorder at three years following treatment: can the definition of recovery be extended to include high functioning heavy drinkers?
Authors: Witkiewitz Katie , Wilson Adam D. , Pearson Matthew R. , Montes Kevin S. , Kirouac Megan , Roos Corey R. , Hallgren Kevin A. , Maisto Stephen A. 
Published: August 2018

AbstractBackground and AimsRecovery from alcohol use disorder (AUD) is often narrowly defined by abstinence from alcohol and improvements in functioning (e.g. mental health, social functioning, employment). This study used latent profile analysis to examine variability in recovery outcomes, defined by alcohol use, alcohol‐related problems and psychosocial functioning at 3 years following treatment. Secondary analysis investigated pre‐treatment, post‐treatment and 1‐ and 3‐year post‐treatment covariate predictors of the latent profiles.DesignSecondary analysis of data from a randomized clinical trial.SettingUnited States.ParticipantsWe used data from the out‐patient arm of Project MATCH (n = 806; 29.7% female, 22.2% non‐white).MeasurementsRecovery was defined by latent profile analyses including measures of psychosocial functioning and life satisfaction (Psychosocial Functioning Inventory), unemployment and mental health (Addiction Severity Index), alcohol and other drug use (Form 90) and alcohol‐related consequences (Drinker Inventory of Consequences) 3 years following treatment. Mixture modeling was used to examine correlates of profiles.FindingsWe identified four profiles at 3 years following treatment: (1) poor functioning frequent heavy drinkers, (2) poor functioning infrequent heavy drinkers, (3) high functioning occasional heavy drinkers and (4) high‐functioning infrequent non‐heavy drinkers. There were relatively few differences on indicators of functioning and treatment‐related variables between the high functioning infrequent non‐heavy drinkers and the high‐functioning occasional heavy drinkers, other than high‐functioning occasional heavy drinkers having lower alcohol dependence severity [odds ratio (OR) = 0.94, 95% confidence interval (CI) = 0.90, 0.98], fewer post‐treatment coping skills (OR = 0.54, 95% CI = 0.32, 0.90) and lower 3‐year post‐treatment abstinence self‐efficacy (OR = 0.37, 95% CI = 0.28, 0.49) and Alcoholics Anonymous (AA) involvement (OR = 0.87, 95% CI = 0.85, 0.99). The two high‐functioning profiles showed the greatest improvements in functioning from baseline through the 3‐year follow‐up, whereas the low‐functioning profiles showed the least amount of improvement. High‐functioning occasional heavy drinkers had higher purpose in life than the poor‐functioning profiles.ConclusionsSome individuals who engage in heavy drinking following treatment for alcohol use disorder may function as well as those who are mostly abstinent with respect to psychosocial functioning, employment, life satisfaction and mental health.
Long‐term oncological outcomes of patients with negative sentinel lymph node in vulvar cancer. Comparative study with conventional lymphadenectomy
Authors: Rodríguez‐Trujillo Adriano , Fusté Pere , Paredes Pilar , Mensión Eduard , Agustí Núria , Gil‐Ibáñez Blanca , del Pino Marta , González‐Bosquet Eduardo , Torné Aureli 
Published: August 2018

AbstractIntroductionThe aim of this study was to compare oncological outcomes and morbidity in patients with early‐stage vulvar cancer with negative sentinel lymph node (SLN) biopsy vs negative inguinofemoral lymphadenectomy (IFL).Material and methodsStudy with retrospectively collected data in patients with squamous cell vulvar carcinomas ≤ 4 cm without suspected inguinofemoral lymph node metastases. Only patients with negative nodes after histopathology procedure were followed. Patients who underwent only SLN were compared with patients who underwent IFL ± SLN to compare recurrences, survival rates and morbidity.ResultsNinety‐three patients were eligible for follow up: 42 with negative SLN and 51 with negative IFL ± SLN. The median follow‐up period was 60.4 months (range 6.7‐160.7). The rate of isolated first groin recurrence was 4.8% in patients with negative SLN and 2.0% in patients with negative IFL ± SLN (P = 0.587) and the rates of first isolated local recurrence were 28.6% and 31.4%, respectively (P = 0.823). Only 1 patient (2.4%) in the group of negative SLN had distant recurrence. The disease‐specific survival rate at 5 years was 83.3% in the negative SLN group and 92.2% in the negative IFL ± SLN group (P = 0.214). We observed a higher rate of wound breakdown and infection after IFL than SLN biopsy (17.6% vs 10.6%; P = 0.020) and lymphedema (33.3% vs 0%; P < 0.001).ConclusionsWe report in the same population of patients with early‐stage vulvar cancer that SLN biopsy does not have significantly higher rates of groin recurrences or lower survival rates compared with IFL. Moreover, the SLN procedure has less morbidity, which should encourage gynecologists to abandon IFL.
Does virginiamycin supplementation affect the metabolism and performance of Nellore bulls grazing under low and high gain rates?
Authors: Costa João Paulo R. , De Jesus Raphael B. , Oliveira Ivanna M. , Resende Flávio D. , Siqueira Gustavo R. , Malheiros Euclides B. 
Published: August 2018

AbstractThis study aimed to evaluate the effect of virginiamycin on the metabolism and performance of growing Nellore bulls under low and high gain rates on pasture. In experiment 1, 80 Nellore bulls (age = 12 ± 2 months, body weight = 258 ± 15 kg) were assigned to 16 paddocks in a 2 × 2 randomized block factorial arrangement. In experiment 2, 12 cannulated Nellore bulls were assigned to three 4 × 4 balanced Latin squares. The factors were: (1) mineral salt without or with virginiamycin, and (2) low or high gain rate. No interaction was noted between factors (p > .10). Animals fed virginiamycin had greater average daily gain (14%, p < .01), body weight (11 kg, p = .05), plasma nonesterified fatty acid (20%, p < .01), serum calcium concentration (2.62%, p = .04), and total protozoa (p = .03) and had the same bacterial proportion (p > .27). Animals with a low gain rate had greater serum urea concentration (19.6%, p < .01) and ruminal ammonia nitrogen (62%, p < .01). Thus, virginiamycin increases the performance and changes the metabolism of growing Nellore bulls under low and high gain rates on pasture.
Motor development in school‐age children is associated with the home environment including socioeconomic status
Authors: Ferreira Luciana , Godinez Ignacio , Gabbard Carl , Vieira José Luiz Lopes , Caçola Priscila 
Published: August 2018

AbstractThe aim of the present study was to examine how the home environment, including socioeconomic status (SES), affects motor development in school‐age children. Seven hundred seven children (332 boys and 375 girls) aged between 6 and 10 years participated in the study. Motor Development was determined using the Bruininks–Oseretsky Test of Motor Proficiency‐Second Edition. Parents answered the Middle Childhood Home Observation Measurement of the Environment (HOME) Inventory, and Brazilian Association of Market Research Institutes Questionnaire (for SES). Children from “Adequate” homes (HOME score), compared with “Less Adequate,” displayed better motor behavior. Mediation and moderation analysis revealed that motor development increased as SES increased. The proportion of variance in motor development explained by SES increased from 9% to 13% when the home was added as a mediation variable. We also found that the effect of SES on motor development was moderated by age. For older children, the effect was lower than for younger children. The best model used SES as the predictor, HOME as the mediator, and AGE as the moderator variable and explained 17% of the variance in motor development. In summary, these findings suggest that, like previous reports with young children, the HOME environment and SES may play an important role in motor development of school‐age children. Our findings encourage the assessment of the home and interventions that take into account the home environment to improve motor development in school‐age children.
Infusion ofex-vivoexpanded human TCR-αβ+ double-negative regulatory T cells delays onset of xenogeneic graft-versus-host disease
Authors: Achita P , Dervovic D , Ly D , Lee J B , Haug T , Joe B , Hirano N , Zhang L 
Published: August 2018

SummaryDespite the demonstration of potent immunosuppressive function of T cell receptor (TCR)-αβ+ double-negative regulatory T cells (DN Tregs), scarce numbers and lack of effective expansion method limit their clinical applications. Here we describe an approach that allows for ∼3500-fold ex-vivo expansion of human DN Tregs within 3 weeks with &gt; 97% purity. Ex-vivo-expanded DN Tregs suppress proliferation of polyclonally stimulated autologous T and B cells in vitro through direct cell-to-cell contact. In vivo, we demonstrate for the first time that infusion of human DN Tregs delayed an onset of xenogeneic graft-versus-host disease (GVHD) significantly in a humanized mouse model. Furthermore, preincubation of ex-vivo-expanded DN Tregs with a mechanistic target of rapamycin (mTOR) inhibitor rapamycin enhanced their immune regulatory function further. Taken together, this study demonstrates that human DN Tregs can be expanded ex vivo to therapeutic numbers. The expanded DN Tregs can suppress proliferation of T and B cells and attenuate GVHD, highlighting the potential clinical use of DN Tregs to mitigate GVHD.
HDAC inhibitors modulate innate immune responses to micro-organisms relevant to chronic mucocutaneous candidiasis
Authors: Rösler B , Wang X , Keating S T , Joosten L A B , Netea M G , van de Veerdonk F L 
Published: August 2018

Summary
Signal transducer and activator of transcription 1 (STAT-1) gain-of-function (GOF) mutations cause chronic mucocutaneous candidiasis (CMC), a disease associated with Candida albicans and Staphylococcus aureus infection. Patients suffer from dysegulated immune responses due to aberrant cell programming and function. We investigated the effect of inhibitory molecules targeting histone deacetylases (HDACi) on the immune responses of peripheral blood mononuclear cells (PBMCs) of healthy controls and patients with CMC towards microbes relevant for CMC. PBMCs cells were pretreated with HDACi and challenged with C. albicans or S. aureus. Innate and adaptive cytokines were measured in cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). We assessed the effect of HDAC inhibitors on T helper type 1 (Th1) and Th17 cells and measured STAT-1 and STAT-3 phosphorylation using flow cytometry. Panobinostat, a pan-HDAC inhibitor, strongly inhibits innate and adaptive cytokines upon challenge with C. albicans or S. aureus. Specific inhibitors (entinostat or RGFP966) also had a tendency to lower production of most innate cytokines in CMC patient cells. Entinostat and RGFP966 increased the production of interleukin (IL)-22 specifically after S. aureus challenge in patient cells. In healthy and control cells, entinostat and RGFP966 treatment down-regulated STAT-1 phosphorylation while pSTAT-3 levels remained stable. HDACi modulate cytokine production in response to C. albicans and S. aureus. Pan-inhibitors lower overall cytokine production, whereas specific inhibitors confer a selective effect. Entinostat and RGFP966 are promising therapeutic candidates to treat STAT-1 GOF due to their capacity to restore IL-22 production and decrease STAT-1 phosphorylation; however, their inhibition of innate cytokines poses a possible risk to secondary infections.
Roflumilast enhances cisplatin‐sensitivity and reverses cisplatin‐resistance of ovarian cancer cells via cAMP/PKA/CREB‐FtMt signalling axis
Authors: Gong Shipeng , Chen Yongning , Meng Fanliang , Zhang Yadi , Li Chanyuan , Zhang Guangping , Huan Wu , Wu Fei 
Published: August 2018

AbstractObjectiveWe previously demonstrated the roflumilast inhibited cell proliferation and increased cell apoptosis in ovarian cancer. In this study, we aimed to investigate the roles of roflumilast in development of cisplatin (DDP)‐sensitive and ‐resistant ovarian cancer.MethodsOVCAR3 and SKOV3 were selected and the corresponding DDP‐resistant cells were constructed. Cell viability, proliferation, apoptosis, cycle were performed. Expression cAMP, PKA, CREB, phosphorylation of CREB and FtMt were detected. The roles of roflumilast in development of DDP‐sensitive and ‐resistant ovarian cancer were confirmed by xenograft model.ResultsRoflumilast + DDP inhibited cell proliferation, and induced cell apoptosis and G0/G1 arrest in OVCAR3 and SKOV3 cells, roflumilast induced expression of FtMt, the activity of cAMP and PKA and phosphorylation of CREB in ovarian cancer cells and the above‐effect were inhibited by H89. Downregulation of CREB inhibited the roflumilast‐increased DDP sensitivity of ovarian cancer cells, and the roflumilast‐induced FtMt expression and phosphorylation of CREB. Also, roflumilast reversed cisplatin‐resistance, and induced expression of FtMt and activation of cAMP/PKA/CREB in DDP‐resistant ovarian cancer cells. Similarly, treated with H89 or downregulation of CREB inhibited the changes induced by roflumilast. In vivo, roflumilast inhibited the development of SKOV3 or SKOV3‐DDP‐R xenograft models.ConclusionsRoflumilast enhanced DDP sensitivity and reversed the DDP resistance of ovarian cancer cells via activation of cAMP/PKA/CREB pathway and upregulation of the downstream FtMt expression, which has great promise in clinical treatment.
MicroRNA‐1258 suppresses tumour progression via GRB2/Ras/Erk pathway in non‐small‐cell lung cancer
Authors: Jiang Wei , Wei Ke , Pan Chunfeng , Li Hong , Cao Jing , Han Xu , Tang Yu , Zhu Shichao , Yuan Weiwei , He Yaozhou , Xia Yang , Chen Liang , Chen Yijiang 
Published: August 2018

AbstractObjectivesLung cancer is still a disease with high morbidity and mortality in the world. MicroRNAs have been proven to act as an indispensable role in the reuse of multiple solid tumours. Although miR‐1258 plays a vital role in suppressing metastasis in breast cancer and gastric cancer, the specific biological function of miR‐1258 in non‐small‐cell lung cancer remains unclear.MethodsThe differential expression of miR‐1258 in NSCLC tissues and corresponding paracancerous tissues was detected by qRT‐PCR and ISH. Flow cytometry and CCK‐8, EdU, tubule formation, and senescence assays were performed, and xenograft models were studied to explore the function of miR‐1258. Potential targets of miR‐1258 were verified by dual luciferase reporter assay, qRT‐PCR, IHC and Western blotting.ResultsIn vitro and in vivo gain‐ and loss‐of‐function assays suggested that miR‐1258 inhibits NSCLC cell proliferation and induces senescence and apoptosis. The luciferase reporter assay, IHC and Western blotting analysis showed that GRB2 is one of the direct targets of miR‐1258. The GRB2 overexpression plasmid can reverse the functional changes after overexpression of miR‐1258. In contrast, miR‐1258 inhibitor significantly reversed si‐GRB2‐induced GRB2 down‐regulation. Mechanistically, overexpression of miR‐1258 inhibits GRB2 expression and then leads to inactivation of the Ras/Erk oncogenic pathway.ConclusionsOur results indicate that miR‐1258 can suppress NSCLC progression by targeting the GRB2/Ras/Erk pathway, which may lead to different insights into potential biomarkers and novel therapeutic strategies for NSCLC patients.
Current treatments and trials in malignant pleural mesothelioma
Authors: Bibby Anna C. , Maskell Nick A. 
Published: August 2018

AbstractObjectivesThis article aims to review the evidence from recent clinical trials in mesothelioma, and to provide an overview of relevant clinical trials that are currently in progress.Data sourceOvid MEDLINE, 1946 to present.Study SelectionClinical trials of therapeutic interventions were considered for inclusion, regardless of phase. Of 258 papers identified in the literature search, 88 were potentially eligible based on abstract screening. Following evaluation of full‐text articles, 35 were selected for inclusion in the review.ResultsSince the original trial that demonstrated the efficacy of pemetrexed and cisplatin in mesothelioma, multiple trials have been conducted that have further informed management options. Anti‐angiogenesis agents such as bevacizumab and nintedanib appear promising as adjuncts to first‐line chemotherapy. Meanwhile, immunotherapy, anti‐mesothelin agents and molecular targeted therapies are potential areas for development, with ongoing trials promising to deliver interesting results over the next few years. Current evidence does not support surgical intervention; however, investigations are ongoing as to the role of extended pleurectomy/decortication, and surgery in the context of trapped lung. Finally radiotherapy is effective as a palliative measure for pain control, but is not indicated prophylactically to prevent the development of procedure tract metastases.ConclusionA large amount of high‐quality mesothelioma research has been conducted in the past decade. As a result, several new therapies are likely to become available in clinical practice in the near future. With multiple trials ongoing, the horizon for patients with mesothelioma looks brighter than ever before.
Digital mapping of a soil profile
Authors: Zhang Y. , Hartemink A. E. 
Published: August 2018

SummaryDetailed information on soil profiles is required for site characterization, soil mapping, studies on pedogenesis, soil–landscape modelling and soil classification. In this study, we used digital soil mapping techniques to map the profile wall of an Alfisol (90‐cm depth × 100‐cm width). Geochemical data (sampled at 10 cm × 10 cm) and digital images (resolution 1 cm × 1 cm) were used as input data in models that predicted a range of properties across the soil profile. Fuzzy c‐means clustering was applied to the profile and colour maps, and a confusion index was calculated. The colour coordinates were strongly correlated with SOC (soil organic carbon), sand and silt contents, and weathering indices. Random forest using the RGB model (R2 = 0.57, RMSE (root mean square error) = 2.41) showed less accurate prediction of SOC content than random forest using the CIE L*a*b* (R2 = 0.84, RMSE = 1.57) and HSV, hue, saturation, chroma (R2 = 0.85, RMSE = 1.46) models. Detailed profile maps showed considerable within‐horizon variation and identified animal holes, roots and limestone fragments. Colour and profile maps of soil properties and weathering indices matched field‐delineated soil horizons. Clusters obtained by soil properties and weathering indices represented the field‐delineated horizons and had the largest overall accuracy (P = 0.85 and 0.86, respectively). The confusion index showed that the horizons had wavy and somewhat irregular boundaries. We conclude that colour coordinates are useful for predicting and mapping soil properties in soil profiles. Random forest can be used to produce high‐resolution soil profile maps, and fuzzy c‐means clustering is useful for delineating soil horizons.HighlightsWe investigated the use of digital images in soil horizon delineation and within soil horizon variation
We used various colour models to map soil profile properties and define horizons
Colour and profile maps of soil properties and weathering indices matched field delineated soil horizons.
Random forest can produce high‐resolution soil profile maps, and fuzzy c‐means clustering can delineate soil horizons
Isolation and identification of potassium‐releasing bacteria in soil and assessment of their ability to release potassium for plants
Authors: Sarikhani M. R. , Oustan S. , Ebrahimi M. , Aliasgharzad N. 
Published: August 2018

SummaryThe application of potassium (K)‐releasing microorganisms is a promising approach for increasing K availability in soil. The objectives of this study were to isolate and characterize the K‐releasing bacteria (KRB) and to evaluate their contribution to the solubilization of K from muscovite and biotite, and to the assimilation of released K by tomato in a pot culture experiment. Soil samples were screened in both solid and liquid Aleksandrov media to isolate bacteria with the potential to release K from biotite and muscovite. Our results fromin‐vitroexperiments revealed that more K was released in treatments with KRB than in the uninoculated media (control). Under the best conditions an increase of 188 and 127% was obtained for biotite and muscovite, respectively; among the isolates with the largest releasing ability it was 49 mg l−1. The most efficient bacteria were identified as thePseudomonasgenus. Results of the pot culture experiment showed that the concentration and content of K in plant tissue were considerably more than those in any of the controls with no living organisms present. Results revealed that significantly more biomass was accumulated and K acquired in most pots treated with bacterial strains than in the control, especially forPseudomonassp. strain S10‐3. This treatment increased K concentation and content by more than 50 and 70%, respectively, in tomato aerial tissue. Further research is necessary to examine the effects of these bacterial strains on the mobilization of K‐bearing minerals under field conditions.HighlightsThe aim was to determine if bacterial isolates can accelerate K release from micas for plants.We investigated the potential of some isolated bacteria to solubilize K from muscovite and biotite.Identification of efficient isolates showed that KRB belonged to thePseudomonasgenus.Pseudomonassp. strain S10‐3 increased K concentration in tomato aerial tissue by more than 50%.
Regulation of 25‐hydroxyvitamin D‐1‐hydroxylase and 24‐hydroxylase in keratinocytes by PTH and FGF23
Authors: Wu Wenlin , Fan Hong , Jiang Yi , Liao Liyan , Li Lusha , Zhao Juan , Zhang Huiling , Shrestha Chandrama , Xie Zhongjian 
Published: August 2018

AbstractRenal 25‐hydroxyvitamin D‐1α‐hydroxylase (1αOHase, CYP27B1) and 24‐hydroxylase (24OHase, CYP24A1) are tightly regulated. However, little is known about the regulation of 1α(OH)ase and 24(OH)ase in extrarenal tissue such as the epidermis. This study was to determine the roles of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF 23) in the regulation of 1α(OH)ase and 24(OH)ase in epidermal keratinocytes as well as epidermal keratinocyte proliferation and differentiation. The results showed that PTH increased the protein level of 1α(OH)ase in human epidermal keratinocyte cell line HaCaT, but had no effect on the level of 24(OH)ase. The effect of PTH on 1α(OH)ase was blocked by the PKC inhibitor. Treatment with FGF23 decreased mRNA and protein levels of 1α(OH)ase and increased mRNA and protein levels of 24(OH)ase in HaCaT cells. The effect of FGF23 on 1α(OH)ase and 24(OH)ase was blocked by the mitogen‐activated protein kinase/extracellular regulated protein kinase (MAPK/ERK) inhibitor. In addition, treatment with PTH enhanced levels of differentiation markers including keratin 1, involucrin, loricrin, and filaggrin but reduced levels of BrdU incorporation in HaCaT cells. These effects were inhibited by the PKC inhibitor. FGF23 enhanced proliferation of HaCaT cells, but reduced levels of early differentiation markers including keratin 1 and involucrin and enhanced levels of the later differentiation markers including loricrin and filaggrin. These results suggest that PTH stimulates 1α(OH)ase expression and differentiation of HaCaT cells and inhibits proliferation via PKC. The data also suggest that FGF23 inhibits 1α(OH)ase expression and stimulates 24(OH)ase expression via MAPK/ERK. In addition, FGF23 enhances proliferation and late differentiation and inhibits early differentiation of HaCaT keratinocytes.