bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory Markers and Incidence of Hospitalization With Infection in Chronic Kidney Disease
Authors: Ishigami Junichi , Taliercio Jonathan , I  Feldman Harold , Srivastava Anand , Townsend Raymond , L  Cohen Debbie , Horwitz Edward , Rao Panduranga , Charleston Jeanne , Fink Jeffrey C , Ricardo Ana C , Sondheimer James , Chen Teresa K , Wolf Myles , Isakova Tamara , Appel Lawrence J , Matsushita Kunihiro ,   for the CRIC Study Investigators
Published: October 2019

Persons with chronic kidney disease (CKD) are at high risk of infection. While low-grade inflammation could impair immune response, it is unknown whether inflammatory markers are associated with infection risk in this clinical population. Using 2003–2013 data from the Chronic Renal Insufficiency Cohort Study (3,597 participants with CKD), we assessed the association of baseline plasma levels of 4 inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 receptor antagonist (IL-1RA), and transforming growth factor-β (TGF-β)) with incident hospitalization with major infection (pneumonia, urinary tract infection, cellulitis and osteomyelitis, and bacteremia and sepsis). During follow-up (median 7.5 years), 36% (n = 1,290) had incident hospitalization with major infection. In multivariable Cox analyses with each inflammatory marker modeled as a restricted cubic spline, higher levels of IL-6 and TNF-α were monotonically associated with increased risk of hospitalization with major infection (for 95th vs. 5th percentile, hazard ratio = 2.11 (95% confidence interval: 1.68, 2.66) for IL-6 and 1.88 (95% confidence interval: 1.51, 2.33) for TNF-α), while corresponding associations for IL-1RA or TGF-β were nonsignificant. Thus, higher plasma levels of IL-6 and TNF-α, but not IL-1RA or TGF-β, were significantly associated with increased risk of hospitalization with major infection. Future studies should investigate whether inflammatory pathways that involve IL-6 and TNF-α increase susceptibility to infection among individuals with CKD.
Implementing Evidence-Based Practice in a Dutch Social Work Organisation: A Shared Responsibility
Authors: van der Zwet Renske J M , Beneken genaamd Kolmer Deirdre M , Schalk René , Van Regenmortel Tine
Published: October 2019

This article presents the findings from a case study, exploring the factors that support and impede implementation of evidence-based practice (EBP) in a Dutch social work organisation that has recently committed to EBP. Qualitative data were gathered from semi-structured interviews with ten staff members and twelve social workers (service providers for adults and families). The organisational model for EBP implementation, recently developed by Plath, was used to examine how EBP was implemented and the factors that support and impede it. Findings revealed that EBP occurs predominantly at the organisational level. Research & Development (R&D) staff take responsibility for the key steps of gathering, appraising and translating research insights into practice activities, whilst social workers are primarily involved in implementing interventions. R&D is also involved in the internal evaluation of interventions in order to support ongoing practice development. Several factors affecting EBP implementation and facilitative strategies have been identified. Most of these are congruent with the organisational model for EBP implementation, with the exception of two impacting factors (negative attitudes about EBP and an organisational culture that values and encourages innovation and learning) and one facilitative strategy (research partnerships). These findings were used to develop the model further.
Genetic diversity and reproductive biology of the dioecious and epiphytic bromeliad Aechmea mariae-reginae (Bromeliaceae) in Costa Rica: implications for its conservation
Authors: Cascante-Marín Alfredo , Trejos Christian , Madrigal Ruth , Fuchs Eric J
Published: October 2019

Ecological traits and pollination mode associated with dioecious sexual expression in plants are likely to influence their reproductive success and levels of genetic diversity. Dioecy is an uncommon condition in Bromeliaceae. Currently, there is limited information on the reproductive ecology and genetics of dioecious and epiphytic bromeliads. Therefore, we studied the reproductive biology and genetic diversity of the epiphytic and dioecious bromeliad Aechmea mariae-reginae in Costa Rica. Flowering of pistillate and staminate plants in one population showed high synchrony and were pollinated by non-hermit hummingbirds. Sex ratio was biased to males (3.5:1). Fruit set was relatively high (68%) but there was high female reproductive variance (C. V. = 59.7%). The species is capable of parthenocarpic fruit production. Using eight nuclear microsatellite markers and six populations, we found moderate to high levels of genetic variation (HE = 0.571–0.726). Populations showed significant genetic structure (G'ST = 0.385) and Bayesian population assignment grouped them into lowland and montane clusters. Isolated montane populations had slightly lower genetic diversity probably due to lower effective population size caused by biased sex ratios and recent habitat fragmentation that limits long-distance pollinator movements and results in isolation by distance. If habitat fragmentation and isolation persist, populations in montane habitats may be at higher risk of decline and extinction.
Revisiting ‘brain modes’ in a new computational era: approaches for the characterization of brain-behavioural associations
Authors: Toba Monica N , Godefroy Olivier , Rushmore R Jarrett , Zavaglia Melissa , Maatoug Redwan , Hilgetag Claus C , Valero-Cabré Antoni
Published: October 2019

The study of brain-function relationships is undergoing a conceptual and methodological transformation due to the emergence of network neuroscience and the development of multivariate methods for lesion-deficit inferences. Anticipating this process, in 1998 Godefroy and co-workers conceptualized the potential of four elementary typologies of brain-behaviour relationships named ‘brain modes’ (unicity, equivalence, association, summation) as building blocks able to describe the association between intact or lesioned brain regions and cognitive processes or neurological deficits. In the light of new multivariate lesion inference and network approaches, we critically revisit and update the original theoretical notion of brain modes, and provide real-life clinical examples that support their existence. To improve the characterization of elementary units of brain-behavioural relationships further, we extend such conceptualization with a fifth brain mode (mutual inhibition/masking summation). We critically assess the ability of these five brain modes to account for any type of brain-function relationship, and discuss past versus future contributions in redefining the anatomical basis of human cognition. We also address the potential of brain modes for predicting the behavioural consequences of lesions and their future role in the design of cognitive neurorehabilitation therapies.
Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence
Authors: Lett Tristram A , Vogel Bob O , Ripke Stephan , Wackerhagen Carolin , Erk Susanne , Awasthi Swapnil , Trubetskoy Vassily , Brandl Eva J , Mohnke Sebastian , Veer Ilya M , Nöthen Markus M , Rietschel Marcella , Degenhardt Franziska , Romanczuk-Seiferth Nina , Witt Stephanie H , Banaschewski Tobias , Bokde Arun L W , Büchel Christian , Quinlan Erin B , Desrivières Sylvane , Flor Herta , Frouin Vincent , Garavan Hugh , Gowland Penny , Ittermann Bernd , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Nees Frauke , Papadopoulos-Orfanos Dimitri , Paus Tomáš , Poustka Luise , Fröhner Juliane H , Smolka Michael N , Whelan Robert , Schumann Gunter , Tost Heike , Meyer-Lindenberg Andreas , Heinz Andreas , Walter Henrik ,   IMAGEN consortium
Published: October 2019

Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2–94.3; P < 0.005), and up to 3.0% in IntegraMooDS (F1,725 = 10.0–21.0; P < 0.005). The association between polygenic scores and g-factor was partially mediated by SA and CT in prefrontal, anterior cingulate, insula, and medial temporal cortices in both samples (PFWER-corrected < 0.005). The variance explained by mediation was up to 0.75% in IMAGEN and 0.77% in IntegraMooDS. Our results provide evidence that cumulative genetic load influences g-factor via cortical structure. The consistency of our results across samples suggests that cortex morphology could be a novel potential biomarker for neurocognitive dysfunction that is among the most intractable psychiatric symptoms.
The contribution of sleep to social inequalities in cardiovascular disorders: a multi-cohort study
Authors: Petrovic Dusan , Haba-Rubio José , de Mestral Vargas Carlos , Kelly-Irving Michelle , Vineis Paolo , Kivimäki Mika , Nyberg Solja , Gandini Martina , Bochud Murielle , Vollenweider Peter , d’Errico Angelo , Barros Henrique , Fraga Silvia , Goldberg Marcel , Zins Marie , Steptoe Andrew , Delpierre Cyrille , Heinzer Raphael , Carmeli Cristian , Chadeau-Hyam Marc , Stringhini Silvia ,   for The Lifepath Consortium
Published: October 2019

Aims

Sleep disturbances exhibit a strong social patterning, and inadequate sleep has been associated with adverse health outcomes, including cardiovascular disorders (CVD). However, the contribution of sleep to socioeconomic inequalities in CVD is unclear. This study pools data from eight European cohorts to investigate the role of sleep duration in the association between life-course socioeconomic status (SES) and CVD.

Methods and results

We used cross-sectional data from eight European cohorts, totalling 111 205 participants. Life-course SES was assessed using father’s and adult occupational position. Self-reported sleep duration was categorized into recommended (6–8.5 h/night), long (>8.5 h/night), and short (<6 h/night). We examined two cardiovascular outcomes: coronary heart disease (CHD) and stroke. Main analyses were conducted using pooled data and examined the association between life-course SES and CVD, and the contribution of sleep duration to this gradient using counterfactual mediation. Low father’s occupational position was associated with an increased risk of CHD (men: OR = 1.19, 95% CI [1.04; 1.37]; women: OR = 1.25, 95% CI [1.02; 1.54]), with marginal decrease of the gradient after accounting for adult occupational position (men: OR = 1.17, 95% CI [1.02; 1.35]; women: OR = 1.22, 95% CI [0.99; 1.52]), and no mediating effect by short sleep duration. Low adult occupational position was associated with an increased risk of CHD in both men and women (men: OR = 1.48, 95% CI [1.14; 1.92]; women: OR = 1.53, 95% CI [1.04; 2.21]). Short sleep duration meaningfully contributed to the association between adult occupational position and CHD in men, with 13.4% mediation. Stroke did not exhibit a social patterning with any of the variables examined.

Conclusion

This study suggests that inadequate sleep accounts to a meaningful proportion of the association between adult occupational position and CHD, at least in men. With sleep increasingly being considered an important cardiovascular risk factor in its own terms, our study additionally points to its potential role in social inequalities in cardiovascular disease.
Diagnostic criteria and symptom grading for delayed gastric conduit emptying after esophagectomy for cancer: international expert consensus based on a modified Delphi process
Authors: Konradsson M , van Berge Henegouwen M I , Bruns C , Chaudry M A , Cheong E , Cuesta M A , Darling G E , Gisbertz S S , Griffin S M , Gutschow C A , van Hillegersberg R , Hofstetter W , Hölscher A H , Kitagawa Y , van Lanschot J J B , Lindblad M , Ferri L E , Low D E , Luyer M D P , Ndegwa N , Mercer S , Moorthy K , Morse C R , Nafteux P , Nieuwehuijzen G A P , Pattyn P , Rosman C , Ruurda J P , Räsänen J , Schneider P M , Schröder W , Sgromo B , Van Veer H , Wijnhoven B P L , Nilsson M
Published: October 2019

Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air–fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have ‘quite a bit’ or ‘very much’ of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: ‘not at all’, ‘a little’, ‘quite a bit’, or ‘very much’, generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process.
Short- and mid-term outcomes of robotic versus thoraco-laparoscopic McKeown esophagectomy for squamous cell esophageal cancer: a propensity score-matched study
Authors: Yang Y , Zhang X , Li B , Hua R , Yang Y , He Y , Ye B , Guo X , Sun Y , Li Z
Published: October 2019

Controversy exists on the advantages of robotic McKeown esophagectomy (RME) versus thoraco-laparoscopic McKeown esophagectomy (TLME). The aim was to evaluate the short- and mid-term outcomes of RME and TLME in the treatment of patients with esophageal squamous cell carcinoma (ESCC). A consecutive series of 652 patients, 280 in RME and 372 in TLME, who underwent minimally invasive McKeown esophagectomy for ESCC at our department from November 2015 to June 2018 was analyzed. A propensity score-matched comparison with clinicopathological covariates was performed between the two groups. Complications were categorized based on the Esophagectomy Complications Consensus Group (ECCG) recommendation. To identify the recurrence, all patients with R0 resection were followed with a median follow-up period of 20.2 months (range 1–33 months). After propensity score matching, 271 patients were identified for each cohort. In the matched cohorts, two patients died within 90 days in TLME, whereas no patients died in RME. RME was associated with similar intraoperative blood loss (P = 0.895), but with shorter surgical duration (244.5 vs. 276.0 min, P < 0.001), shorter thoracic duration (85.0 vs. 102.9 min, P < 0.001) and lower thoracic conversions (0.7% vs. 5.9%, P = 0.001). In spite of the similar results on total and thoracic lymph nodes dissection, RME yielded more lymph nodes along recurrent laryngeal nerve (4.8 vs. 4.1, P = 0.012), as well as the higher incidence of recurrent nerve injury (29.2% vs. 15.1%, P < 0.001) when compared to TLME. Tumor recurrence occurred in 30 patients and was locoregional only in 9 (3.5%) patients, systemic only in 17 (6.7%) patients, and combined in 4 (1.6%) patients in RME, while in 26 patients and was locoregional only in 10 (10.6%) patients, systemic only in 7 (2.8%) patients, and combined in 9 (3.6%) patients in TLME. RME was associated with a lower rate of mediastinal lymph nodes recurrence (2.0% vs. 5.3%, P = 0.044). Overall and disease-free survival was not different between the two cohorts (P = 0.097 and P = 0.248, respectively). RME was shown to be a safe and oncologically effective approach with favorable short- and mid-term outcomes in the treatment of patients with ESCC.
Simultaneous deblending and data reconstruction to supply proper time-lapse data sets throughout the field life in a cost-effective and efficient manner
Authors: Nakayama Shotaro , Blacquière Gerrit
Published: October 2019

Acquisition of multiple seismic data sets at different moments in time is capable of satisfying the continuously increasing demand for high-quality subsurface images to reveal both static and dynamic elements during the field development. However, in practice, challenges of pursuing this strategy lie in different perspectives related to budgetary, operational and regulatory constraints. Seismic surveys performed in a compressed manner in time and/or space can provide high-quality seismic data sets in a cost-effective and productive manner. This way of acquisition normally accompanies decompression of recorded data such as deblending and/or data reconstruction. The performance of the recovery process is of fundamental importance in determining the technical success of compressed measurements. Our proposed approach aims at realizing the benefits from compression in data acquisition, contributing to cost and efficiency, while recovering deblended and reconstructed data of sufficient quality. The approach deals jointly with deblending and data reconstruction via a sparse inversion in the frequency–wavenumber domain, coupled with constraints on causality and coherency. Additionally, we formulate a single objective function aimed at sharing static information among vintages and, at the same time, at extracting dynamic changes in the reservoir of interest according to prior subsurface information. We apply the proposed approach to both synthetic and real data. A comparison with a strategy that independently recovers compressed data sets demonstrates the viability of the proposed simultaneous method to effectively enhance the quality of recovered data and extract reliable time-lapse signatures.
Follow-up Care for Breast Cancer Survivors
Authors: Ruddy Kathryn J , Herrin Jeph , Sangaralingham Lindsey , Freedman Rachel A , Jemal Ahmedin , Haddad Tufia C , Allen Summer V , Hieken Tina , Boughey Judy C , Ganz Patricia A , Havyer Rachel D , Shah Nilay D
Published: October 2019

Breast cancer survivorship guidelines recommend at least annual follow-up visits, yet the degree to which this occurs in clinical practice is uncertain. Claims data from a US commercial insurance database (OptumLabs) were used to identify women treated with curative intent surgery for newly diagnosed breast cancer between 2006 and 2014. In 25 035 women, median follow-up was 3 years. In the second year after surgery, 9.6% of the patients did not visit a primary care provider, an oncologist, or a surgeon (guideline-nonadherent). The guideline-nonadherent proportion increased from 7.8% in women diagnosed in 2006 to 12.2% in those diagnosed in 2014 (two-sided Wald P < .001). During years 2–6, guideline-nonadherence was also associated with older age, nonwhite race, no radiation, no chemotherapy, no endocrine therapy, and increasing time after surgery. There is a substantial and increasing rate of inadequate follow-up among breast cancer survivors. This has the potential to impair outcomes.
Large-scale analysis of the cassava transcriptome reveals the impact of cold stress on alternative splicing
Authors: Li Shuxia , Yu Xiang , Cheng Zhihao , Zeng Changying , Li Wenbin , Zhang Liangsheng , Peng Ming
Published: October 2019

Alternative splicing is an essential post-transcriptional regulatory mechanism that can impact mRNA stability and protein diversity of eukaryotic genomes. Although numerous forms of stress-responsive alternative splicing have been identified in model plants, a large-scale study of alternative splicing dynamics under abiotic stress conditions in cassava has not been conducted. Here, we report the parallel employment of isoform-Seq, ssRNA-Seq, and Degradome-Seq to investigate the diversity, abundance, and fate of alternatively spliced isoforms in response to cold and drought stress. We identified 38 164 alternative splicing events, among which 3292 and 1025 events were significantly regulated by cold and drought stress, respectively. Intron retention was the most abundant subtype of alternative splicing. Global analysis of splicing regulators revealed that the number of their alternatively spliced isoforms and the corresponding abundance were specifically modulated by cold stress. We found that 58.5% of cold-regulated alternative splicing events introduced a premature termination codon into the transcripts, and 77.6% of differential alternative splicing events were detected by Degradome-Seq. Our data reveal that cold intensely affects both quantitative and qualitative aspects of gene expression via alternative splicing pathways, and advances our understanding of the high complexity and specificity of gene regulation in response to abiotic stresses.

Alternative splicing is responsible for reprogramming of the transcriptome and the sensitivity of cassava plants to cold.
Hsp70 plays a role in programmed cell death during the remodelling of leaves of the lace plant (Aponogeton madagascariensis)
Authors: Rowarth Nathan M , Dauphinee Adrian N , Denbigh Georgia L , Gunawardena Arunika Hlan
Published: October 2019

Lace plant leaves utilize programmed cell death (PCD) to form perforations during development. The role of heat shock proteins (Hsps) in PCD during lace plant leaf development is currently unknown. Hsp70 amounts were measured throughout lace plant leaf development, and the results indicate that it is highest before and during PCD. Increased Hsp70 amounts correlate with raised anthocyanin content and caspase-like protease (CLP) activity. To investigate the effects of Hsp70 on leaf development, whole plants were treated with either of the known regulators of PCD [reactive oxygen species (ROS) or antioxidants] or an Hsp70 inhibitor, chlorophenylethynylsulfonamide (PES-Cl). ROS treatment significantly increased Hsp70 2-fold and CLP activity in early developing leaves, but no change in anthocyanin and the number of perforations formed was observed. Antioxidant treatment significantly decreased Hsp70, anthocyanin, and CLP activity in early leaves, resulting in the fewest perforations. PES-Cl (25 μM) treatment significantly increased Hsp70 4-fold in early leaves, while anthocyanin, superoxide, and CLP activity significantly declined, leading to fewer perforations. Results show that significantly increased (4-fold) or decreased Hsp70 amounts lead to lower anthocyanin and CLP activity, inhibiting PCD induction. Our data support the hypothesis that Hsp70 plays a role in regulating PCD at a threshold in lace plant leaf development.

Hsp70 affects anthocyanin content and caspase-like protease activity, and helps regulate PCD during the remodelling of leaves of lace plant, Aponogeton madagascariensis.
Emerging concepts of potassium homeostasis in plants
Authors: Srivastava Ashish Kumar , Shankar Alka , Nalini Chandran Anil Kumar , Sharma Manisha , Jung Ki-Hong , Suprasanna Penna , Pandey Girdhar K
Published: October 2019

The review highlights the need to broaden our scope of K+ research from single elements to multielements, from coding sequences to whole genes, and from isolated plants to the whole ecosystem.
Exosomal microRNAs and other non-coding RNAs as colorectal cancer biomarkers: a review
Authors: Francavilla Antonio , Turoczi Szimonetta , Tarallo Sonia , Vodicka Pavel , Pardini Barbara , Naccarati Alessio
Published: October 2019

The circulating human transcriptome, which includes both coding and non-coding RNA (ncRNA) molecules, represents a rich source of potential biomarkers for colorectal cancer (CRC) that has only recently been explored. In particular, the release of RNA-containing extracellular vesicles (EVs), in a multitude of different in vitro cell systems and in a variety of body fluids, has attracted wide interest. The role of RNA species in EVs is still not fully understood, but their capacity to act as a form of distant communication between cells and their higher abundance in association with cancer demonstrated their relevance. In this review, we report the evidence from both in vitro and human studies on microRNAs (miRNAs) and other ncRNA profiles analysed in EVs in relation to CRC as diagnostic, prognostic and predictive markers. The studies so far highlighted that, in exosomes, the most studied category of EVs, several miRNAs are able to accurately discriminate CRC cases from controls as well as to describe the progression of the disease and its prognosis. Most of the time, the in vitro findings support the miRNA profiles detected in human exosomes. The expression profiles measured in exosomes and other EVs differ and, interestingly, there is a variability of expression also among different subsets of exosomes according to their proteic profile. On the other hand, evidence is still limited for what concerns exosome miRNAs as early diagnostic and predictive markers of treatment. Several other ncRNAs that are carried by exosomes, mostly long ncRNAs and circular RNAs, seem also to be dysregulated in CRC. Besides various technical challenges, such as the standardisation of EVs isolation methods and the optimisation of methodologies to characterise the whole spectrum of RNA molecules in exosomes, further studies are needed in order to elucidate their relevance as CRC markers.
The ProteomeXchange consortium in 2020: enabling ‘big data’ approaches in proteomics
Authors: Deutsch Eric W , Bandeira Nuno , Sharma Vagisha , Perez-Riverol Yasset , Carver Jeremy J , Kundu Deepti J , García-Seisdedos David , Jarnuczak Andrew F , Hewapathirana Suresh , Pullman Benjamin S , Wertz Julie , Sun Zhi , Kawano Shin , Okuda Shujiro , Watanabe Yu , Hermjakob Henning , MacLean Brendan , MacCoss Michael J , Zhu Yunping , Ishihama Yasushi , Vizcaíno Juan A
Published: October 2019

The ProteomeXchange (PX) consortium of proteomics resources (http://www.proteomexchange.org) has standardized data submission and dissemination of mass spectrometry proteomics data worldwide since 2012. In this paper, we describe the main developments since the previous update manuscript was published in Nucleic Acids Research in 2017. Since then, in addition to the four PX existing members at the time (PRIDE, PeptideAtlas including the PASSEL resource, MassIVE and jPOST), two new resources have joined PX: iProX (China) and Panorama Public (USA). We first describe the updated submission guidelines, now expanded to include six members. Next, with current data submission statistics, we demonstrate that the proteomics field is now actively embracing public open data policies. At the end of June 2019, more than 14 100 datasets had been submitted to PX resources since 2012, and from those, more than 9 500 in just the last three years. In parallel, an unprecedented increase of data re-use activities in the field, including ‘big data’ approaches, is enabling novel research and new data resources. At last, we also outline some of our future plans for the coming years.
Pivotal clinical trials, meta-analyses and current guidelines in the treatment of hyperkalemia
Authors: Bianchi Stefano , Regolisti Giuseppe
Published: October 2019

Hyperkalemia (HK) is the most common electrolyte disturbance observed in patients with advanced stages of chronic kidney disease (CKD), is a potentially life-threatening clinical condition due to an increased risk of fatal arrhythmias, and strongly impacts the quality of life and prognosis of CKD patients. Moreover, while renin–angiotensin–aldosterone system inhibitors (RAASIs) represent the most cardio-nephro-protective drugs used in clinical practice, the treatment with these drugs per se increases serum potassium (sK) values, particularly when heart failure and diabetes mellitus coexist. In fact, the onset or recurrence of HK is frequently associated with not starting, down-titrating or withdrawing RAASIs, and is an indication to begin renal replacement treatment in end-stage renal disease. Current strategies aimed at preventing and treating chronic HK are still unsatisfactory, as evidenced by the relatively high prevalence of HK also in patients under stable nephrology care, and even in the ideal setting of randomized clinical trials. Indeed, dietary potassium restriction, the use of sodium bicarbonate or diuretics, the withdrawal or down-titration of RAASIs, or the administration of old potassium binders, namely sodium polystyrene sulphonate and calcium polystyrene sulphonate, have limited efficacy and are poorly tolerated; therefore, these strategies are not suitable for long-term control of sK. As such, there is an important unmet need for novel therapeutic options for the chronic management of patients at risk for HK. The development of new potassium binders may change the treatment landscape in the near future. This review summarizes the current evidence on the treatment of chronic HK in cardio-renal patients.
Smoking Topography Characteristics During a 6-Week Trial of Very Low Nicotine Content Cigarettes in Smokers With Serious Mental Illness
Authors: Denlinger-Apte Rachel L , Donny Eric C , Lindgren Bruce R , Rubin Nathan , Goodwin Christine , DeAtley Teresa , Colby Suzanne M , Cioe Patricia A , Hatsukami Dorothy K , Tidey Jennifer W
Published: October 2019

Introduction

A nicotine-reduction policy could have major benefits for smokers with serious mental illness (SMI). However, potential unintended consequences, such as compensatory smoking, should be considered to ensure that such a policy does not negatively affect this population. The purpose of this secondary analysis was to examine the impact of smoking very low nicotine content (VLNC) cigarettes for 6 weeks on smoking topography characteristics, indicators of compensatory smoking, among smokers with SMI.

Aims and Methods

After a baseline usual brand smoking phase, smokers with SMI (N = 58) were randomly assigned under double-blind conditions to receive either VLNC (0.4 mg nicotine per g tobacco) or normal nicotine content (NNC; 15.8 mg nicotine per g tobacco) research cigarettes for 6 weeks. During two study visits scheduled 6 weeks apart, participants smoked either their usual brand (baseline) or assigned study cigarettes (postrandomization) through a handheld smoking topography device. Univariate analysis of variance compared smoking topography indices with cigarette condition (VLNC vs. NNC) as the between-subjects factor with corresponding baseline topography results included as covariates.

Results

At week 6, participants in the VLNC condition smoked fewer puffs per cigarette and had shorter interpuff intervals compared to participants in the NNC condition (ps < .05). There were no differences between research cigarette conditions at week 6 for cigarette volume, puff volume, puff duration, peak flow rate, or carbon monoxide boost.

Conclusions

Findings are consistent with acute VLNC cigarette topography studies and indicate that a nicotine-reduction policy is unlikely to lead to compensation among smokers with SMI.

Implications

Given the high smoking rates among people with SMI, understanding how a nicotine-reduction policy may affect this population is critically important. When considering the smoking topography results as a whole, smokers with SMI did not engage in compensatory smoking behavior when using VLNC cigarettes during a 6-week trial. Study findings suggest that compensatory smoking is not likely to occur among smokers with SMI if nicotine content is lowered to minimally addictive levels.
Cytomegalovirus seropositivity is independently associated with cardiovascular disease in non-dialysis dependent chronic kidney disease
Authors: Karangizi A H K , Chanouzas D , Fenton A , Moss P , Cockwell P , Ferro C J , Harper L
Published: October 2019

Background

Cardiovascular disease (CVD) is the leading cause of early death in patients with chronic kidney disease (CKD). Previous work has described an association between Cytomegalovirus (CMV) seropositivity and CVD amongst patients with dialysis dependent end stage renal disease. Whether CMV seropositivity is associated with CVD in non-dialysis dependent CKD has not been established.

Aim

Investigate whether past CMV infection is associated with prevalent CVD in patients with non-dialysis dependent CKD.

Design

A retrospective observational study using the Renal Impairment in Secondary Care cohort, a study evaluating bio-clinical determinants of outcomes in patients with progressive CKD.

Methods

We assayed cryopreserved serum samples collected at inception for anti-CMV IgG antibodies from 764 patients with stages 2 to 5 CKD (pre-dialysis) and investigated its relationship with prevalent CVD.

Results

Median estimated glomerular filtration was 24 ml/min/1.73 m2 (IQR 19–32). Sixty-eight percent of patients were CMV seropositive. CMV seropositivity was associated with older age, non-Caucasian ethnicity, diabetes and higher social deprivation index score. On univariable analysis, CMV seropositivity correlated with higher systolic blood pressure (P = 0.044), prevalent CVD (P < 0.001), ischaemic heart disease (P < 0.001) and cerebrovascular disease (P = 0.022). On multivariable analysis, CMV seropositive patients nearly twice as likely to have CVD compared to seronegative patients [Odds Ratio (OR) = 1.998, CI 1.231–3.242, P = 0.005].

Conclusions

In patients with non-dialysis CKD, CMV seropositivity is independently associated with a higher prevalence of CVD.
Natural history of excessive daytime sleepiness: a population-based 5-year longitudinal study
Authors: Jaussent I , Morin C M , Ivers H , Dauvilliers Y
Published: October 2019

Study Objectives

To document the rates of persistent, remitted, and intermittent excessive daytime sleepiness (EDS) in a longitudinal 5-year community study of adults and to assess how changes in risk factors over time can predict improvement of daytime sleepiness (DS).

Methods

Participants were recruited in 2007–2008 as part of a population-based epidemiological study implemented in Canada. They completed postal assessments at baseline and at each yearly follow-up. An Epworth Sleepiness Scale total score >10 indicated clinically significant EDS; a 4-point reduction between two consecutive evaluations defined DS improvement. Socio-demographic, lifestyle, health characteristics, and sleep-related measures (e.g. insomnia symptoms, sleep duration, sleep medication) were self-reported at each time point. Cox proportional-hazard models were used to predict EDS and DS remissions over 5 years.

Results

Among the 2167 participants, 33% (n = 714) met criteria for EDS at baseline, of whom 33% had persistent EDS, 44% intermittent EDS, and 23% remitted EDS over the follow-up. Furthermore, 61.4% of 2167 initial participants had stable DS, 27.1% sustained DS improvement and 8.5% transient improvement over the follow-up. The main predictors of EDS remission or DS improvement were normal weight, taking less hypnotics, having hypertension, increased nighttime sleep duration, and decreased insomnia, and depressive symptoms.

Conclusions

EDS waxes and wanes over time with frequent periods of remission and is influenced by behavioral characteristics and changes in psychological, metabolic, and nighttime sleep patterns. Targeting these predictors in future interventions is crucial to reduce DS in the general adult population.
Bi-directional relations between stress and self-reported and actigraphy-assessed sleep: a daily intensive longitudinal study
Authors: Yap Yang , Slavish Danica C , Taylor Daniel J , Bei Bei , Wiley Joshua F
Published: October 2019

Study Objectives

Stress is associated with poor and short sleep, but the temporal order of these variables remains unclear. This study examined the temporal and bi-directional associations between stress and sleep and explored the moderating role of baseline sleep complaints, using daily, intensive longitudinal designs.

Methods

Participants were 326 young adults (Mage = 23.24 ± 5.46), providing >2,500 nights of sleep altogether. Prospective total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE) were measured using actigraphy and sleep diaries. Perceived stress was reported three times daily between: 11:00–15:00, 15:30–19:30, and 20:00–02:00. Sleep complaints were measured at baseline using the PROMIS sleep disturbance scale. Within- and between-person sleep and stress variables were tested using cross-lagged multilevel models.

Results

Controlling for covariates and lagged outcomes, within-person effects showed that higher evening stress predicted shorter actigraphic and self-reported TST (both p < .01). Conversely, shorter actigraphic and self-reported TST predicted higher next-day stress (both p < .001). Longer self-reported SOL and WASO (both p < .001), as well as lower actigraphic (p < .01) and self-reported SE (p < .001), predicted higher next-day stress. Between-person effects emerged only for self-reported TST predicting stress (p < .01). No significant results were found for the moderating role of baseline sleep complaints.

Conclusions

Results demonstrated bi-directional relations between stress and sleep quantity, and a consistent direction of worse sleep quantity and continuity predicting higher next-day stress. Results highlighted within-individual daily variation as being more important than between-individual differences when examining sleep and daytime functioning associations.
Muscle-evoked Potentials After Electrical Stimulation to the Brain in Patients Undergoing Spinal Surgery are Less Affected by Anesthetic Fade With Constant-voltage Stimulation Than With Constant-current Stimulation
Authors: Tanaka Masato , Shigematsu Hideki , Kawaguchi Masahiko , Hayashi Hironobu , Takatani Tsunenori , Iwata Eiichiro , Okuda Akinori , Morimoto Yasuhiko , Kawasaki Sachiko , Masuda Keisuke , Yamamoto Yusuke , Tanaka Yasuhito
Published: October 2019

Study Design.

A prospective, within-subject study was conducted.

Objective.

We aimed to compare the influence of anesthetic fade under maximum stimulation conditions between constant-current and constant-voltage stimulation techniques.

Summary of Background Data.

The monitoring of muscle-evoked potentials after electrical stimulation to the brain [Br(E)-MSEP)] is useful for assessing the integrity of spinal cord motor tracts during major spine surgery. Nonetheless, Br(E)-MSEP responses are known to deteriorate over the duration of surgeries performed under general anesthesia. This phenomenon is known as anesthetic fade.

Methods.

We recruited 117 patients undergoing various spinal surgeries from the cervical to the lumbar level. We excluded 29 cases with insufficient data. The decrease rate of the Br(E)-MSEP amplitude for each muscle was examined. Br(E)-MSEP monitoring with constant-current and constant-voltage stimulations at the C3 and C4 electrode positions was applied. Compound muscle action potentials (CMAPs) were bilaterally recorded from the abductor pollicis brevis, deltoid, abductor hallucis, tibialis anterior, gastrocnemius, and quadriceps muscles. We defined the decrease rate as follows: (initial CMAPs-final CMAPs)/initial CMAPs × 100. Differences in the decrease rate were evaluated between stimulators, limbs (upper vs. lower), and operative time group (lowest quartile vs. highest quartile).

Results.

The overall decrease rate (across all muscles) increased as the operative time increased, and the rate was higher in the lower limbs than in the upper limbs. In addition, the overall decrease rate was lower with constant-voltage stimulation than with constant-current stimulation. Furthermore, the decrease rate for constant-current stimulation was significantly higher than that for constant-voltage stimulation, regardless of the operative time.

Conclusion.

The CMAP waveform with constant-voltage stimulation is less susceptible to anesthetic fade than that with constant-current stimulation, even during long surgeries.

Level of Evidence: 3
Sinomenine sensitizes human gastric cancer cells to cisplatin through negative regulation of PI3K/AKT/Wnt signaling pathway
Authors: Liu Ying , Liu Changqing , Tan Ting , Li Shang , Tang Shunyu , Chen Xingyin
Published: October 2019

Sinomenine (SIN) has been reported its antitumor effects on various types of human cancers, but there is no available information regarding the antitumor effects of SIN and cisplatin on gastric cancer. Here, we examined the antitumor effects of SIN combined with cisplatin on gastric cancer cells as well as the underlying biological mechanisms. CCK-8 assay and Calcusyn 2.0 software analysis, Hoechst 33258 staining and flow cytometry, transwell assay showed that SIN and cisplatin synergistically inhibited growth, induced apoptosis, and suppressed invasion than did either drug alone in gastric cancer cells. Interestingly, no change in the AKT level was found, whereas SIN and cisplatin led to a dramatic decrease in p-AKT level compared with either alone treatment. SIN and cisplatin further decreased the Bcl-2, procaspase-3, and β-catenin, but increased Bax, cleaved dcaspase 3, MMP9, and MMP2 in combined group than in either alone group. Immunofluorescence staining showed again a significant decrease in nucleus β-catenin was found in combined group. These data suggested that SIN sensitizes human gastric cancer cells to cisplatin through negative regulation of PI3K/AKT/Wnt signaling pathway. In conclusion, SIN and cisplatin exerted synergistic antitumor effects in gastric cancer cells and might constitute a promising therapeutic approach for gastric cancer.
Estimating the Impact of Words Used by Physicians in Advance Care Planning Discussions: The “Do You Want Everything Done?” Effect
Authors: DiDiodato Giulio
Published: October 2019

Objectives:

To estimate the probability of a substitute decision maker choosing to withdraw life-sustaining therapy after hearing an affirmative patient response to the phrase “Do you want everything done?”

Design:

Discrete choice experiment.

Setting:

Single community hospital in Ontario.

Subjects:

Nonrandom sampling of healthcare providers and the public.

Intervention:

Online survey.

Measurements and Main Results:

Of the 1,621 subjects who entered the survey, 692 consented and 432 completed the survey. Females comprised 73% of subjects. Over 95% of subjects were under 65 years old, and 50% had some intensive care–related exposure. Healthcare providers comprised 29% of the subjects. The relative importance of attributes for determining the probability of withdraw life-sustaining therapy by substitute decision makers was as follows: stated patient preferences equals to 23.4%; patient age equals to 20.6%; physical function prognosis equals to 15.2%; length of ICU stay equals to 14.4%; survival prognosis equals to 13.8%; and prognosis for communication equals to 12.6%. Using attribute level utilities, the probability of an substitute decision maker choosing to withdraw life-sustaining therapy after hearing a patient answer in the affirmative “Do you want everything done?” compared with “I would not want to live if I could not take care of myself” was 18.8% (95% CI, 17.2–20.4%) versus 59.8% (95% CI, 57.6–62.0%) after controlling for all the other five attribute levels in the scenario: age greater than 80 years; survival prognosis less than 1%; length of ICU stay greater than 6 months; communication equals to unresponsive; and physical equals to bed bound.

Conclusions:

Using a discrete choice experiment survey, we estimated the impact of a commonly employed and poorly understood phrase physicians may use when discussing advance care plans with patients and their substitute decision makers on the subsequent withdraw life-sustaining therapies. This phrase is predicted to dramatically reduce the likelihood of withdraw life-sustaining therapy even in medically nonbeneficial scenarios and potentially contribute to low-value end-of-life care and outcomes. The immediate cessation of this term should be reinforced in medical training for all healthcare providers who participate in advance care planning.
A Protocol that Mandates Postoxygenator and Arterial Blood Gases to Confirm Brain Death on Venoarterial Extracorporeal Membrane Oxygenation
Authors: Ihle Joshua F. , Burrell Aidan J. C. , Philpot Steve J. , Pilcher David V. , Murphy Deirdre A. , Pellegrino Vincent A.
Published: October 2019

The apnea test (AT) during clinical brain death (BD) testing does not account for different arterial gas tensions on veno-arterial extracorporeal membrane oxygenation (V-A ECMO). We aimed to develop a protocol and now report our experience with three patients. The protocol was developed and implemented in 2015 at a quaternary center in Australia, measures both right radial and postoxygenator carbon dioxide (CO2) and oxygen (O2) gas tensions during the AT, incorporates regular gas sampling and a gradual reduction in fresh gas flow to ensure patient oxygenation. Patient 1 remained apneic despite both right radial and postoxygenator CO2 gas tensions >60 mmHg. Patient 2, despite having CO2 levels in a right radial arterial sample high enough to diagnose BD, postoxygenator CO2 remained <60 mmHg. Patient 2 did not breathe but radiological tests confirmed BD. Patient 3 showed respiratory effort but only once CO2 levels rose high enough in both right radial and postoxygenator samples. No patient was hypoxic during the AT. Performance of a reliable AT on V-A ECMO requires measurement of both right radial and postoxygenator blood gases. A protocol, which measures both blood gas values, is feasible to implement, while being both safe and easy to perform.