bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical significance of perineural invasion in patients with de novo metastatic prostate cancer
Authors: Zhao J. , Chen J. , Zhang M. , Tang X. , Sun G. , Zhu S. , Liu J. , Zhang H. , Zhang X. , Yin X. , Zhao P. , Zhu X. , Ni Y. , Dai J. , Shen P. , Chen N. , Zeng H. 
Published: January 2019

AbstractBackgroundThe clinical value of perineural invasion (PNI) in patients with localized prostate cancer (PCa) is widely explored. However, its role in metastatic PCa (mPCa) remains unknown.ObjectivesWe aim to investigate the clinical significance of PNI in patients with mPCa.Materials and methodsData of 515 mPCa patients between 2012 and 2018 were retrospectively studied. PNI and its intensity were identified by prostate biopsy. The prognostic value of PNI was evaluated by Kaplan–Meier curves and Cox proportional‐hazards model.ResultsPerineural invasion was detected in 170/515 (33.0%) cases. Among them 73/170 (42.9%) and 97/170 (57.1%) harbored unifocal PNI (uni‐PNI) and multifocal PNI (multi‐PNI), respectively. Compared to patients without PNI, those with PNI had statistically shorter castration‐resistant PCa‐free survival (CFS) and numerically shorter overall survival (OS) (mCFS: 15.4‐ vs. 18.5‐Mo, p = 0.015; mOS: 63.8‐ vs. 71.4‐Mo, p = 0.108). Patients harboring multi‐PNI were associated with poorer clinical outcomes than those with uni‐PNI (mCFS: 12.4‐ vs. 18.0‐Mo, p = 0.040; mOS: 39.7‐Mo vs. NR, p = 0.018) or those without PNI (mCFS: 12.4‐ vs. 18.5‐Mo, p = 0.002; mOS: 39.7‐ vs. 71.4‐Mo, p = 0.002). Totally, neither uni‐PNI nor multi‐PNI was an independent risk factor impacting survival outcomes in multivariate analyses. While remarkably, for patients with favorable/intermediate‐risk mPCa, multi‐PNI was an independent adverse prognosticator for both CFS and OS (CFS: HR: 1.705, 95% CI: 1.029–2.825, p = 0.038; OS: HR: 3.294, 95% CI: 1.464–7.413, p = 0.004).Discussion and ConclusionThis study filled the blank of the clinical significance of PNI in mPCa. We found that multi‐PNI could distinguish men with relatively poor prognosis from patients initially regarded as with favorable survival outcomes by other prognosticators, and thus, avoid disease underestimation in this group of patients. Our finding would help physicians have a deeper understanding of the heterogeneity of mPCa and make better individualized therapeutic strategy.
Living with tinnitus and the health care journey: An interpretative phenomenological analysis
Authors: Marks Elizabeth , Smith Paula , McKenna Laurence 
Published: January 2019

ObjectivesTinnitus is a very common experience, and although usually mild, in a significant proportion of people, it is intrusive, persistent, and disabling. This paper explores the lived experience of chronic disabling tinnitus, with the aim of understanding how distress and chronicity occur, and what might help to reduce this.DesignNine individuals were interviewed 6 months after completing mindfulness‐based cognitive therapy (MBCT) as part of a randomized controlled trial. The results reported here focus on their experiences of tinnitus before receiving MBCT.MethodsData were collected through semi‐structured, face‐to‐face interviews with a clinical psychologist, and an interpretative phenomenological analysis approach was used.ResultsTwo supraordinate themes emerged. ‘Living with tinnitus’ describes a range of significant and profound life changes that result from the condition. Tinnitus can be a life‐altering condition affecting thoughts, emotions, attention, behaviour, and the social world. ‘The health care journey’ shows how chronic distress was intensified by unhelpful health communications and alleviated by helpful consultations.ConclusionsTinnitus is a biopsychosocial condition, and associated distress is affected by cognitive, behavioural, attentional, and social factors. The individuals’ initial reactions to tinnitus interact with the responses of others, including health care professionals. The burden of tinnitus could be reduced by developing early interventions that offer clear, helpful, and realistic information about tinnitus and appropriate treatments.
Statement of contribution

What is already known on this subject?

Tinnitus is the experience of an internal sound without an external sound source.

It can be troubling, disabling, and chronic and usually has no clear medical cause or medical treatment, but psychological interventions are promising.

Cognitive, behavioural, and attentional factors play a role in distress and therapeutic outcome.

Clinical encounters are improved by aligning patient and clinician and sharing decision‐making.

What does this study add?

It is the first in‐depth study exploring how tinnitus distress and health care systems interact.

It shows how a biopsychosocial approach to tinnitus may reduce tinnitus burden more effectively than a biomedical, diagnostic‐focused approach.

It indicates how effective early health care information could be used to reduce chronic tinnitus distress.
Effects of developmental stress on animal phenotype and performance: a quantitative review
Authors: Eyck Harrison J.F. , Buchanan Katherine L. , Crino Ondi L. , Jessop Tim S. 
Published: January 2019

ABSTRACTDevelopmental stressors are increasingly recognised for their pervasive influence on the ecology and evolution of animals. In particular, many studies have focused on how developmental stress can give rise to variation in adult behaviour, physiology, and performance. However, there remains a poor understanding of whether general patterns exist in the effects and magnitude of phenotypic responses across taxonomic groups. Furthermore, given the extensive phenotypic variation that arises from developmental stressors, it remains important to ascertain how multiple processes may explain these responses. We compiled data from 111 studies to examine and quantify the effect of developmental stress on animal phenotype and performance from juveniles to adulthood, including studies from birds, reptiles, fish, mammals, insects, arachnids, and amphibians. Using meta‐analytic approaches, we show that across all studies there is, on average, a moderate to large negative effect of developmental stress exposure (posterior mean effect: |d| = −0.51) on animal phenotype or performance. Additionally, we demonstrate that interactive effects of timing of stressor onset and the duration of exposure to stressors best explained variation in developmental stress responses. Animals exposed to stressors earlier in development had more‐positive responses than those with later onset, whereas longer duration of exposure to a stressor caused responses to be stronger in magnitude. However, the high amount of heterogeneity in our results, and the low degree of variance explained by fixed effects in both the meta‐analysis (R2= 0.034) and top‐ranked meta‐regression model (R2= 0.02), indicate that phenotypic responses to developmental stressors are likely highly idiosyncratic in nature and difficult to predict. Despite this, our analyses address a critical knowledge gap in understanding what effect developmental stress has on phenotypic variation in animals. Additionally, our results highlight important environmental and proximate factors that may influence phenotypic responses to developmental stressors.
Intravenous immune globulin affects cytokine production in T lymphocytes and monocytesjmacrophages
Authors: Andersson J , Skansén-Saphir U , Sparrelid E , Andersson U 
Published: January 2019

SummaryImmune globulin for intravenous use (IVIG) has been used in many inflammatory conditions due to its immunomodulatory potential. The effector mechanisms are incompletely understood. This study dealt with the effects of IVIG on cytokine production in vitro. Cytokine synthesis was identified at the single-cell level using cytokine-specific MAb and indirect immunocytochemical techniques. Peripheral blood mononuclear cells (PBMC) were stimulated for 96 h by immobilized anti-CD3 MAb or by a combination of a protein kinase C activator (PMA) and a calcium ionophore (ionomycin). The addition of IVIG (6 mg/ml) caused a marked inhibition of proliferation and blast transformation despite unaffected cell survival. Anti-CD3-stimulatcd cultures containing IVIG exhibited a significant inhibition of production of T-cell derived lymphokines IL-2, IL-10, TNF-β, IFN-1 and TNF-α (made by both monocytes and T cells), while synthesis of the monokinc IL-8 was significantly increased. The expression of IL-2 receptors was significantly suppressed. Similar but transient inhibition of most T-cell products (IL-2, IL-3, IL-4, IL-5, IL-10, TNF-β and GM-CSF) was noted in the PMA/ionomycin-containing cultures. In contrast, no effects were found on IFN-γ or TNF-α production. The supcrantigen streptococcal pyrogenic exotoxin-A (SPE-A) induced vigorous cell activation and extensive cytokine synthesis. IVIG was added either at the beginning or 24 h after the initiation of cultures in order to elucidate the importance of direct toxinneutralization. Addition of IVIG from the beginning of cultures induced a strong reduction of blast transformation and an almost complete inhibition of lymphokinc production, in particular of IFN-γ and TNF-β. Supplementation with IVIG 24 h after initiation of cultures also led to a significant decrease in lymphokine synthesis. Monokine production (IL-1α, IL-1β, IL-lra, IL-6 and IL-8) was either unaffected or even increased. These two facts argue against direct antigen-neutralization as being the only mechanism at work. However, in IVIG-exposed PBMC stimulated with LPS, IL-6 production was significantly r,educed. A significant upregulation of IL-lra was noticed in unstimulated PBMC cultured with IVIG. The results in all the experiments did not indicate a cytotoxic effect by IVIG on cell survival and the production of certain cytokines were unaffected. Instead, the authors believe that the results suggest a previously little examined functional link where the humoral immune response may have direct immunoregulatory effects on the cellular immune system.
Intravenous immune globulin therapy of lupus nephritis: use of pathogenic anti-DNA-reactive IgG
Authors: Silvestris F , D'Amore O , Cafforio P , Savino L , Dammacco F 
Published: January 2019

SummaryThe authors have recently shown that antibodies with anti-idiotype (Id) specificity to pathogenic Ids of lupus nephritis may occasionally occur in several intravenous immune globulin (IVIG) preparations because they are present in healthy donors and the healthy relatives of SLE patients. In the present study, the authors purified these anti-Ids and treated two SLE patients with nephritis in parallel with conventional high-dose IVIG management with a commercial preparation (IVIG 6) in three controls for two months. Because pathogenic Ids of anti-DNA molecules, such as both 8·l2 and F4 Ids. show a cationic mobility in isoclectrie focusing, a commercial preparation of IVIG (11) was absorbed on a Sepharose column coupled with DC-305-39 myeloma protein, namely a 8·l2+ and F4+ cationic IgG. Infusion of the eluate (EL-11) induced a prompt resolution of proteinuria levels and an evident decrease of serum levels of anti-DNA antibodies in both patients, whereas in the three controls, proteinuria and anti-DNA antibodies were scarcely reduced. In addition, plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α were also significantly influenced by both treatments. The mean values of both cytokines increased significantly after 1 h and then progressively declined over the next 48 h. It was of interest, however, that the increased TNF-α in the two EL-11-treated patients was significantly lower than in the three controls. The data suggest that reduction of active lupus nephritis by enriched specific anti-Id molecules is the result of two (or perhaps more) mechanisms: suppression of pathogenic idiotypes at the cellular level and improvement in the mesangium of the secretion of antiinflammatory cytokines, such as IL-6. whose defective function is related to the autoimmune disorder.
Composite cardiovascular risk factor target achievement and its predictors in US adults with diabetes: The Diabetes Collaborative Registry
Authors: Fan Wenjun , Song Yang , Inzucchi Silvio E. , Sperling Laurence , Cannon Christopher P. , Arnold Suzanne V. , Kosiborod Mikhail , Wong Nathan D. 
Published: January 2019

AimTo investigate multiple risk factor target attainment in adults with diabetes mellitus (DM) for atherosclerotic cardiovascular disease (ASCVD) prevention and the predictors of such attainment in a contemporary DM registry.MethodsIn the US Diabetes Collaborative Registry we identified patients who were at target for glycated haemoglobin (HbA1c; < 53 mmol/mol (7%) or < 64 mmol/mol (8%) if with ASCVD), LDL cholesterol (< 2.6 mmol/L (100 mg/dL) or < 1.8 mmol/L (70 mg/dL) 1.8 if with ASCVD) and blood pressure (BP; <140/90 mmHg and < 130/80 mmHg as an alternate), and who had non‐smoking status, by sex, race and history of ASCVD. Multiple logistic regression was used to examine predictors of target attainment.ResultsIn 74 393 patients with DM who had available data (mean age 69.0 years, 41.0% women), overall target attainment for HbA1c, BP, LDL cholesterol and non‐smoking status was 73.6%, 69.0% (40.3% for BP <130/80 mmHg), 48.6% and 85.2%, respectively. Only 21.6% (13.0% with BP <130/80 mmHg) were at target for all four measures, and the proportions were higher in men (23.6%) versus women (18.6%) and in white people (22.5%) versus African‐American people (14.7%) and people of other races (20.8%; P < 0.01). A total of 62.4% were on a moderate‐/high‐intensity statin. Age (≥65 years: odds ratio [OR] 1.9, 95% confidence interval [CI] 1.7‐2.0; and 55‐64 years: OR 1.3, 95% CI 1.2‐1.4 vs. <55 years), male sex (OR 1.3, 95% CI 1.3‐1.4), white race (OR 1.4, 95% CI 1.3‐1.5), middle or high income (ORs 1.1, 95% CI 1.1‐1.2 or 1.4, 95% CI 1.4‐1.5, respectively) were associated, and depression (OR 0.9, 95% CI 0.8‐1.0) was inversely associated with meeting all four targets (all P = 0.01 to P < 0.001).ConclusionsIn our US registry of patients with DM, only one in five patients were achieving comprehensive risk factor control. Multifactorial interventions will be necessary to optimize ASCVD risk factor control.
Dapagliflozin and cardiovascular mortality and disease outcomes in a population with type 2 diabetes similar to that of the DECLARE‐TIMI 58 trial: A nationwide observational study
Authors: Norhammar Anna , Bodegård Johan , Nyström Thomas , Thuresson Marcus , Nathanson David , Eriksson Jan W. 
Published: January 2019

AimsTo investigate cardiovascular (CV) safety and event rates for dapagliflozin versus other glucose‐lowering drugs (GLDs) in a real‐world type 2 diabetes population after applying the main inclusion criteria and outcomes from the DECLARE‐TIMI 58 study.MethodsPatients with new initiation of dapagliflozin and/or other GLDs were identified in Swedish nationwide healthcare registries for the period 2013 to 2016. Patients were included if they met the main DECLARE‐TIMI 58 inclusion criteria: age ≥40 years and established CV disease or presence of multiple‐risk factors, e.g. men aged ≥55 years and women aged ≥60 years with hypertension or dyslipidaemia. Propensity scores for the likelihood of dapagliflozin initiation were calculated, then 1:3 matching was carried out. DECLARE‐TIMI 58 outcomes were hospitalization for heart failure (HHF) or CV‐specific mortality, and major adverse CV events (MACE; CV‐specific mortality, myocardial infarction, or stroke). Cox survival models were used to estimate hazard ratios (HRs).ResultsAfter matching, a total of 28 408 new‐users of dapagliflozin and/or other GLDs were identified, forming the population for the present study (henceforth referred to as the DECLARE‐like cohort. The mean age of this cohort was 66 years, and 34% had established CV disease. Dapagliflozin was associated with 21% lower risk of HHF or CV mortality versus other GLDs (HR 0.79, 95% confidence interval [CI] 0.69‐0.92) and had no significant association with MACE (HR 0.90, 95% CI 0.79‐1.03). HHF and CV mortality risks, separately, were lower at HR 0.79 (95% CI 0.67‐0.93) and HR 0.75 (95% CI 0.57‐0.97), respectively. Non‐significant associations were seen for myocardial infarction and stroke: HR 0.91 (95% CI 0.74‐1.11) and HR 1.06 (95% CI 0.87‐1.30), respectively.ConclusionIn a real‐world population similar to those included in the DECLARE‐TIMI 58 study, dapagliflozin was safe with regard to CV outcomes and resulted in lower event rates of HHF and CV mortality versus other GLDs.
Knitting patterns of biodiversity, range size and body size in aquatic beetle faunas: significant relationships but slightly divergent drivers
Authors: Heino Jani , Alahuhta Janne 
Published: January 2019

1. Ecogeographical rules refer to recurring patterns in nature, including the latitudinal diversity gradient (LDG), Rapoport's rule and Bergmann's rule, amongst others. In the present study, the existence of these rules was examined for diving beetles (Coleoptera: Dytiscidae), a family of aquatic predatory beetles.2. Assemblage‐level data were analysed for diving beetles, focusing on species richness, local contribution to beta diversity (LCBD), mean range size and mean body size across the biogeographical provinces of Northern Europe. First, each of these variables was correlated with latitude, and then variation in each variable was modelled using actual environmental variables in boosted regression tree analysis.3. Species richness was found to decrease with latitude, LCBD increased with latitude, mean range size did not show a significant relationship with latitude, and mean body size decreased with latitude. The latter finding was in contrast to Bergmann's rule. The actual environmental variables best predicting variation in these four response variables varied among the models, although they generally included temperature‐related and land use variables as the most influential ones.4. The results obtained in the present study suggest that diving beetles conformed to the LDG, did not follow Rapoport's rule, and showed a reversed latitudinal gradient in the context of Bergmann's rule. In addition, species‐poor provinces harboured ecologically most unique faunas, suggesting that species richness and LCBD are complementary measures of biodiversity.5. Even though general support was not found for most of the ecogeographical rules examined, the findings of the present study are interesting because they suggest that aquatic ectothermic invertebrates may show patterns different from those originally described for terrestrial endothermic vertebrates.
Responses of an endangered brown bear population to climate change based on predictable food resource and shelter alterations
Authors: Penteriani Vincenzo , Zarzo‐Arias Alejandra , Novo‐Fernández Alís , Bombieri Giulia , López‐Sánchez Carlos A. 
Published: January 2019

AbstractThe survival of an increasing number of species is threatened by climate change: 20%–30% of plants and animals seem to be at risk of range shift or extinction if global warming reaches levels projected to occur by the end of this century. Plant range shifts may determine whether animal species that rely on plant availability for food and shelter will be affected by new patterns of plant occupancy and availability. Brown bears in temperate forested habitats mostly forage on plants and it may be expected that climate change will affect the viability of the endangered populations of southern Europe. Here, we assess the potential impact of climate change on seven plants that represent the main food resources and shelter for the endangered population of brown bears in the Cantabrian Mountains (Spain). Our simulations suggest that the geographic range of these plants might be altered under future climate warming, with most bear resources reducing their range. As a consequence, this brown bear population is expected to decline drastically in the next 50 years. Range shifts of brown bear are also expected to displace individuals from mountainous areas towards more humanized ones, where we can expect an increase in conflicts and bear mortality rates. Additional negative effects might include: (a) a tendency to a more carnivorous diet, which would increase conflicts with cattle farmers; (b) limited fat storage before hibernation due to the reduction of oak forests; (c) increased intraspecific competition with other acorn consumers, that is, wild ungulates and free‐ranging livestock; and (d) larger displacements between seasons to find main trophic resources. The magnitude of the changes projected by our models emphasizes that conservation practices focused only on bears may not be appropriate and thus we need more dynamic conservation planning aimed at reducing the impact of climate change in forested landscapes.
Bioaccessibility and antioxidant activity of phenolic compounds in cooked pulses
Authors: Lafarga Tomás , Villaró Silvia , Bobo Gloria , Simó Joan , Aguiló‐Aguayo Ingrid 
Published: January 2019

SummaryThe aim of this study was to evaluate the bioaccessibility of polyphenols and antioxidant activity in cooked pulses and to study the effect of cooking on their total phenolic content (TPC) and antioxidant capacity. Cooked faba beans showed the highest TPC, followed by soybeans and lentils or peas. TPC ranged from 10.4 ± 0.2 to 52.9 ± 0.3 mg/100 g and was positively correlated with antioxidant activity. Cooking resulted in increased TPC and antioxidant activity of the methanolic extracts, caused by cell disruption and improved extraction of polyphenols. Although polyphenols were lost in the cooking water, boiled legumes had more polyphenols than those resulting cooking broths. In vitro gastrointestinal digestion resulted in increased TPC and antioxidant capacity of the extracts. Soybeans showed the highest amount of bioaccessible polyphenols. The release of phenolics from cooked legumes was mainly achieved during the intestinal phase. Literature data may underestimate the TPC and antioxidant capacity of pulses.
Degradation of anti‐nutritional factors and reduction of immunoreactivity of tempeh by co‐fermentation with Rhizopus oligosporus RT‐3 and Actinomucor elegans DCY‐1
Authors: Huang Lu , Wang Chenxi , Zhang Yongzhu , Chen Xiaohong , Huang Zhihai , Xing Guangliang , Dong Mingsheng 
Published: January 2019

SummaryThe effects of solid‐state fermentation with four filamentous fungi (Rhizopus oligosporus, Actinomucor elegans, Neurospora crassa and Rhizopus oryzae) and their combination on the degradation of protein allergens and anti‐nutritional factors (ANFs) of tempeh were evaluated. Glycinin, β‐conglycinin, trypsin inhibitor and flatulence‐causing oligosaccharides were significantly hydrolysed by all assayed strains but the level of reduction of ANFs depended on the strain. ELISA was conducted to evaluate IgE immunoreactivity using sera from soy sensitive individuals. Results revealed that co‐fermentation of R. oligosporus and A. elegans resulted in the highest reduction in IgE immunoreactivity for all sera used and showed greatest degradations on α’, α, β, acidic subunits (100% hydrolysed) and extensive hydrolysis of flatulence‐causing oligosaccharides. Tempeh fermented with R. oligosporus and A. elegans displayed high level of soluble protein and peptide (<10 kD) content. Co‐fermentation of R. oligosporus and A. elegans was proved to be effective in producing hypoallergenic tempeh.