bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community Socioeconomic Deprivation and Nonalcoholic Fatty Liver Disease Severity
Authors: Orkin Sarah , Brokamp Cole , Yodoshi Toshifumi , Trout Andrew T. , Liu Chunyan , Meryum Syeda , Taylor Stuart , Wolfe Christopher , Sheridan Rachel , Seth Aradhna , Bhuiyan Mohammad Alfrad Nobel , Ley Sanita , Arce‐Clachar Ana Catalina , Bramlage Kristin , Kahn Robert , Xanthakos Stavra , Beck Andrew F. , Mouzaki Marialena 
Published: October 2019

ABSTRACTBackground and Objectives:Nonalcoholic fatty liver disease (NAFLD) is linked to obesity. Obesity is associated with lower socioeconomic status (SES). An independent link between pediatric NAFLD and SES has not been elucidated. The objective of this study was to evaluate the distribution of socioeconomic deprivation, measured using an area‐level proxy, in pediatric patients with known NAFLD and to determine whether deprivation is associated with liver disease severity.Methods:Retrospective study of patients <21 years with NAFLD, followed from 2009 to 2018. The patients’ addresses were mapped to census tracts, which were then linked to the community deprivation index (CDI; range 0‐‐1, higher values indicating higher deprivation, calculated from six SES‐related variables available publicly in US Census databases).Results:Two cohorts were evaluated; 1 with MRI (magnetic resonance imaging) and/or MRE (magnetic resonance elastography) findings indicative of NAFLD (n = 334), and another with biopsy‐confirmed NAFLD (n = 245). In the MRI and histology cohorts, the majority were boys (66%), non‐Hispanic (77%–78%), severely obese (79%–80%), and publicly insured (55%–56%, respectively). The median CDI for both groups was 0.36 (range 0.15–0.85). In both cohorts, patients living above the median CDI were more likely to be younger at initial presentation, time of MRI, and time of liver biopsy. MRI‐measured fat fraction and liver stiffness, as well as histologic characteristics were not different between the high‐ and low‐deprivation groups.Conclusions:Children with NAFLD were found across the spectrum of deprivation. Although children from more deprived neighborhoods present at a younger age, they exhibit the same degree of NAFLD severity as their peers from less deprived areas.
Translation and Validation of the Arabic Version of the Caring Nurse-Patient Interaction Scale–Patient Version (CNPI-23P)
Authors: Abu Sharour Loai 
Published: October 2019

Background
Importantly, little is known about the cancer patients’ perceptions about nurses’ caring behaviors in Arab countries (Jordan specifically). This is mainly related to a lack of short Arabic instruments that measure nurse-patient interaction from a caring perspective.

Objective
To translate and validate an Arabic version of the Caring Nurse-Patient Interaction Scale–Patient Version (CNPI-23P).

Methods
The CNPI-23 was translated into Arabic using Brislin’s model of translation. A cross-cultural adaptation and psychometric testing were used to collect the data from patients with cancer through a self-administered questionnaire, which included the Arabic version of CNPI-23P and demographic characteristics. Descriptive statistics, inferential statistics, and exploratory factor analysis were used.

Results
One hundred fifty patients were recruited. A content validity involving experts and 20 patients indicated that the statements were clear, understandable, and in logical and easy order. Reliability analysis of CNPI-23P subscales ranged between 0.71 to 0.91 and 0.95 for the total Arabic version of CNPI-23P. Results of the exploratory factor analysis showed that the 23-item scale score reflecting 4 caring domains with Kaiser-Meyer-Olkin was 0.896, and Bartlett test of sphericity was significant (P < .001).

Conclusion
The Arabic version of CNPI-23P is reliable and valid and can be used in research, clinical, and educational settings in Arabic countries.

Implications for Practice
The Arabic version of CNPI-23P may increase our understanding of cancer patients’ perceptions about nurses’ caring behaviors in Arab countries.
Pediatric Plasma and Platelet Transfusions on Extracorporeal Membrane Oxygenation: A Subgroup Analysis of Two Large International Point-Prevalence Studies and the Role of Local Guidelines*
Authors: Nellis Marianne E. , Saini Arun , Spinella Philip C. , Davis Peter J. , Steiner Marie E. , Tucci Marisa , Cushing Melissa , Demaret Pierre , Stanworth Simon J. , Leteurtre Stephane , Karam Oliver 
Published: October 2019

Objectives:
To describe the indications and thresholds for plasma and platelet transfusions for pediatric extracorporeal membrane oxygenation, to compare responses to these transfusions and to describe institutional protocols directing their administration.

Design:
Subgroup analysis of two prospective, observational studies paired with survey of sites who enrolled subjects into this cohort.

Setting:
Fifty-one PICUs in 13 countries.

Patients:
Children (3 d to 16 yr old) were enrolled if they received a plasma or platelet transfusion while on extracorporeal membrane oxygenation during one of the predefined screening weeks.

Interventions:
None.

Measurements and Main Results:
Forty-eight children on extracorporeal membrane oxygenation received plasma transfusions and 90 received platelet transfusions. Sixty percent of plasma transfusions (29/48) and 79% of the platelet transfusions (71/90) were given for prophylaxis of bleeding. The median (interquartile range) international normalized ratio prior to transfusion, known in 75% of the patients (36/48), was 1.45 (1.20–1.85). The median (interquartile range) total platelet count prior to transfusion, known in all of the patients, was 70 × 109/L (52–90 × 109/L). The international normalized ratio and total platelet count values prior to transfusion did not vary based on bleeding versus nonbleeding indications. The median (interquartile range) reduction in international normalized ratio for mild coagulopathies (international normalized ratio ≤ 2.0) was 0.1 (0.4–0), median (interquartile range) increase in fibrinogen was 0.2 g/L (0.1–0.4 g/L) and median increase in total platelet count was 34 × 109/L (10–74 × 109/L). Through the course of their admission, children supported by extracorporeal membrane oxygenation received a total median (interquartile range) dose of 75 mL/kg (36–159 mL/kg) of plasma transfusions and 92 mL/kg (42–239 mL/kg) of platelet transfusions. Institutional protocols varied but provided guidance for platelet transfusions more commonly.

Conclusions:
Children supported by extracorporeal membrane oxygenation receive large volumes of plasma and platelet transfusions with some institutional guidance in the form of protocols, but significant variation in practice. Interventional studies are necessary to provide evidence to direct the transfusion of hemostatic products in children supported by extracorporeal membrane oxygenation.
The Association Between Marital Status, Coronary Computed Tomography Imaging Biomarkers, and Mortality in a Lung Cancer Screening Population
Authors: Celeng Csilla , Takx Richard A.P. , Lessmann Nikolas , Maurovich-Horvat Pál , Leiner Tim , Išgum Ivana , de Jong Pim A. 
Published: October 2019

Purpose:
The purpose of this study was to elucidate the impact of being unmarried on coronary computed tomography (CT) imaging biomarkers and mortality in a lung cancer screening population.

Materials and Methods:
In this retrospective case-control study, 5707 subjects (3777 married; mean age: 61.9±5.1 y and 1930 unmarried; mean age: 61.9±5.3 y) underwent low-dose CT as part of the National Lung Screening Trial (NLST). The median follow-up time was 6.5 (Q1-Q3: 5.6 to 6.9) years. Being unmarried was defined as never married, widowed, separated, or divorced. Being married was defined as married or living as married. Our primary endpoint was cardiovascular disease (CVD)-related death; our secondary endpoint was all-cause mortality. Coronary CT imaging biomarkers (calcium score, density, and volume) on low-dose chest CT scan were calculated using dedicated automatic software. Weighted Cox proportional-hazards regression was performed to examine the association between marital status and death. Kaplan-Meier curves were generated to visualize subject survival.

Results:
Being unmarried was significantly associated with an increased risk for CVD-related death (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.31-1.91) and all-cause mortality (HR: 1.39; 95% CI: 1.26-1.53), which remained significant even after adjusting for traditional cardiovascular risk factors (HR CVD death: 1.75; 1.44-2.12 and HR all-cause mortality: 1.58; 95% CI: 1.43-1.74) and coronary calcium score (HR CVD death: 1.58; 95% CI: 1.31-1.91 and HR all-cause mortality: 1.40; 95% CI: 1.27-1.54).

Conclusions:
Being unmarried is associated with an increased CVD-related death and all-cause mortality mainly due to cardiovascular etiology. On the basis of this, marital status might be taken into consideration when assessing individuals’ health status.
Patients With Persistently Low MELD-Na Scores Continue to Be at Risk of Liver-related Death
Authors: Mazumder Nikhilesh R. , Atiemo Kofi , Daud Amna , Kho Abel , Abecassis Michael , Levitsky Josh , Ladner Daniela P. 
Published: October 2019

Background.
The vast majority of patients with cirrhosis have low Model for End-Stage Liver Disease–Sodium (MELD-Na) scores; however, the ability for the MELD-Na score to predict patient outcomes at low scores is unclear.

Methods.
Adult patients in a multicenter, Chicago-wide database of medical records with International Classification of Disease, Ninth Edition codes of cirrhosis and without a history of hepatocellular carcinoma were included. Records were linked with the state death registry, and death certificates were manually reviewed. Deaths were classified as “liver-related,” “non-liver-related,” and “non-descript” as adjudicated by a panel comprised of a transplant surgeon, a hepatologist, and an internist. A sensitivity analysis was performed where patients with hepatocellular carcinoma were included.

Results.
Among 7922 identified patients, 3999 patients had MELD-Na scores that were never higher than 15. In total, 2137 (27%) patients died during the study period with higher mortality rates for the patients in the high MELD-Na group (19.4 (41.6%) versus 4.1 (12.6%) per 100 person-y, P < 0.001). The high MELD-Na group died of a liver-related cause in 1142 out of 1632 (70%) as compared to 240 out of 505 (47.5%) deaths in the low MELD-Na group. There was no difference in the distribution of subcategory of liver-related death between low and high MELD-Na groups. Among subclassification of liver-related deaths, the most common cause of death was “Infectious” in both groups.

Conclusions.
Despite persistently low MELD-Na scores, patients with cirrhosis still experience high rates of liver-related mortality.
Antibodies Against ARHGDIB and ARHGDIB Gene Expression Associate With Kidney Allograft Outcome
Authors: Senev Aleksandar , Otten Henny G. , Kamburova Elena G. , Callemeyn Jasper , Lerut Evelyne , Van Sandt Vicky , Kuypers Dirk , Emonds Marie-Paule , Naesens Maarten 
Published: October 2019

Background.
The impact of donor-specific anti-HLA antibodies (DSA) on antibody-mediated rejection (AMR) and kidney allograft failure is well established. However, the relevance of non-HLA antibodies remains unclear.

Methods.
We investigated 13 pretransplant non-HLA antibodies and their association with histology of AMR (AMRh) and kidney allograft failure. We included single kidney recipients (n = 203) with AMRh, according to the Banff 2017 classification and matched AMRh-free controls (n = 219). Non-HLA antibodies were assessed using multiplex Luminex assay.

Results.
Of the selected non-HLA antibodies (against agrin, adipocyte plasma membrane-associated protein, Rho GDP-dissociation inhibitor 2 [ARHGDIB], Rho guanine nucleotide exchange factor 6, angiotensin-II type 1 receptor, endothelin type A receptor, lamin B1, BPI fold-containing family B member 1, peroxisomal trans-2-enoyl-coenzyme A reductase, phospholipase A2 receptor, protein kinase C zeta type, tubulin beta-4B class IVb, vimentin), only antibodies against ARHGDIB (adjusted median fluorescence intensity [aMFI] ≥ 1000), a minor histocompatibility antigen, associated with graft failure, in univariate and multivariate models (hazard ratio = 2.7; 95% confidence interval [CI],1.3-5.4; P = 0.007). There was a 19.5-fold (95% CI, 6.0-63.9; P < 0.0001) increased risk of graft failure in patients positive for both DSA and anti-ARHGDIB antibodies (aMFI ≥ 1000) versus patients negative for both DSA and anti-ARHGDIB antibodies, compared with a 4.4-fold (95% CI, 2.4-8.2; P < 0.0001) increased risk in patients with only DSA, and a 4.1-fold (95% CI, 1.4-11.7; P = 0.009) increased risk in patients with only anti-ARHGDIB antibodies above 2000 aMFI. AMRh associated with increased intrarenal expression of the ARHGDIB gene. In the absence of AMRh and DSA, anti-ARHGDIB antibodies were not clearly associated with graft failure.

Conclusions.
The presence of pretransplant anti-ARHGDIB antibodies has an additive effect in patients with DSA on the risk of graft failure via AMRh. Other investigated non-HLA antibodies, including antibodies against angiotensin-II type 1 receptor, did not contribute to risk stratification and could not explain the histology of AMR in the absence of DSA.
Imlifidase Inhibits HLA Antibody-mediated NK Cell Activation and Antibody-dependent Cell-mediated Cytotoxicity (ADCC) In Vitro
Authors: Ge Shili , Chu Maggie , Choi Jua , Louie Sabrina , Vo Ashley , Jordan Stanley C. , Toyoda Mieko 
Published: October 2019

Background.
Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important pathway responsible for antibody-mediated rejection (AMR). Imlifidase (IdeS) cleaves human IgG into F(ab’)2 and Fc fragments, potentially inhibiting ADCC. Here we examined the effect of IdeS on allo-antibody-mediated NK cell activation (Allo-CFC) and ADCC in vitro.

Methods.
For Allo-CFC, normal whole blood was incubated with third-party peripheral blood mononuclear cells (PBMCs) pretreated with anti-HLA antibody positive (HS) or negative (NC) sera to measure IFNγ+ NK cell%. For ADCC, normal PBMCs were incubated with Farage B (FB) cells with HS or NC sera to measure 7-AAD+ lysed FB cell%. To assess the effect of IdeS on these assays, serum-treated PBMCs (Allo-CFC-1) and serum used for PBMC pretreatment (Allo-CFC-2) in Allo-CFC, and serum used for ADCC were preincubated with IdeS. Sera from IdeS-treated patients were also tested for Allo-CFC (Allo-CFC-3).

Results.
IFNγ+ NK cell% were significantly elevated in HS versus NC sera in Allo-CFC-1 (10 ± 3% versus 2 ± 1%, P = 0.001), Allo-CFC-2 (20 ± 10% versus 4 ± 2%, P = 0.01) and 7AAD+ FB cell% (11 ± 3% versus 4 ± 2%, P = 0.02) in ADCC. These were significantly reduced by IdeS treatment. Patient sera with significantly reduced anti-HLA antibody levels at 1 day postimlifidase lost the capacity to activate NK cells in Allo-CFC-3, but those at 1–3 months postimlifidase regained the capacity.

Conclusions.
IdeS inhibited NK cell activation and ADCC in vitro and in treated patients. These results and reported inhibition of complement activating anti-HLA antibodies by IdeS suggest its possible role in treatment of AMR.
Towards ecologically valid biomarkers: real-life gait assessment in cerebellar ataxia
Authors: Ilg Winfried , Seemann Jens , Giese Martin , Traschütz Andreas , Schöls Ludger , Timmann Dagmar , Synofzik Matthis 
Published: October 2019

AbstractBACKGROUNDWith disease-modifying drugs on the horizon for degenerative ataxias, motor biomarkers are highly warranted. While ataxic gait and its treatment-induced improvements can be captured in laboratory-based assessments, quantitative markers of ataxic gait in real life will help to determine ecologically meaningful improvements.OBJECTIVESTo unravel and validate markers of ataxic gait in real life by using wearable sensors.METHODSWe assessed gait characteristics of 43 patients with degenerative cerebellar disease (SARA:9.4±3.9) compared to 35 controls by 3 body-worn inertial sensors in three conditions: (1) laboratory-based walking; (2) supervised free walking; (3) real-life walking during everyday living (subgroup n=21). Movement analysis focussed on measures of movement smoothness and spatio-temporal step variability.RESULTSA set of gait variability measures was identified which allowed to consistently identify ataxic gait changes in all three conditions. Lateral step deviation and a compound measure of step length categorized patients against controls in real life with a discrimination accuracy of 0.86. Both were highly correlated with clinical ataxia severity (effect size ρ=0.76). These measures allowed detecting group differences even for patients who differed only 1 point in the SARAp&g subscore, with highest effect sizes for real-life walking (d=0.67).CONCLUSIONSWe identified measures of ataxic gait that allowed not only to capture the gait variability inherent in ataxic gait in real life, but also demonstrate high sensitivity to small differences in disease severity - with highest effect sizes in real-life walking. They thus represent promising candidates for quantitative motor markers for natural history and treatment trials in ecologically valid contexts.
Evidence of massive leukemic progenitor expansion in blood during molecular recurrence after TKI discontinuation in chronic myeloid leukemia (CML)
Authors: Turhan Ali G , Hugues Patricia , Sorel Nathalie , Desterke Christophe , Bourhis Jean-Henri , Bennaceur-Griscelli Annelise , Chomel Jean-Claude 
Published: October 2019

ABSTRACTChronic myeloid leukemia (CML) represents one of the major success stories of targeted therapies of the 21st century with the use of tyrosine kinase inhibitors (TKIs). Following discontinuation of TKIs in deep molecular remission context, at least half of the patients experience molecular relapse. Cellular events occurring during this phase are not yet established. In this work, we show a massive amplification of clonogenic progenitors or CFCs (colony-forming cells) in the peripheral blood of patients in molecular recurrence after a TKI discontinuation. We demonstrate, by qRT-PCR analysis on individual and pooled CFCs, that leukemic clonogenic progenitor expansion in the peripheral blood represents the first cellular event before any evidence of cytological change. These findings also suggest that the amplification of the leukemic clone during the first stages of CML takes place not only in the bone marrow but also in the peripheral blood.
Characterising strategy use during the performance of hippocampal-dependent tasks
Authors: Clark Ian A. , Monk Anna M. , Maguire Eleanor A. 
Published: October 2019

ABSTRACTRecalling the past, thinking about the future and navigating in the world are linked with a brain structure called the hippocampus. Precisely how the hippocampus enables these critical cognitive functions is still debated. The strategies people use to perform tasks associated with these functions have been under-studied, and yet such information could augment our understanding of the associated cognitive processes and neural substrates. Here, we devised and deployed an in-depth protocol to examine the explicit strategies used by 217 participants to perform four naturalistic tasks widely acknowledged to be hippocampal-dependent, namely, those assessing scene imagination, autobiographical memory recall, future thinking and spatial navigation. In addition, we also investigated strategy use for three laboratory-based memory tasks, one of which is held to be hippocampal-dependent – concrete verbal paired associates – and two tasks which are likely hippocampal-independent – abstract verbal paired associates and the dead or alive semantic memory test. We found that scene visual imagery was the dominant strategy not only when mentally imagining scenes, but also during autobiographical memory recall, when thinking about the future and during navigation. Moreover, scene visual imagery strategies were used most frequently during the concrete verbal paired associates task, whereas verbal strategies were most prevalent for the abstract verbal paired associates task and the dead or alive semantic memory task. The ubiquity of specifically scene visual imagery use across a range of tasks may attest to its, perhaps underappreciated, importance in facilitating cognition, whilst also aligning with perspectives that emphasise a key role for the hippocampus in constructing scene imagery.
Highly expressed miR-375 is not an intracellular oncogene in Merkel cell polyomavirus-associated Merkel cell carcinoma
Authors: Fan Kaiji , Zebisch Armin , Horny Kai , Schrama David , Becker Jürgen C. 
Published: October 2019

AbstractmiR-375 is a highly abundant miRNA in Merkel cell carcinoma (MCC), in other cancers it acts either as a tumor suppressor or oncogene. While free-circulating miR-375 serves as surrogate marker for tumor burden in patients with advanced MCC, its function within MCC cells has not been established. Nearly complete miR-375 knockdown in MCC cell lines was achieved using antagomiRs via nucleofection. Neither cell viability, growth characteristics nor morphology were altered by this knockdown. miR-375 target genes and related signaling pathways were determined using ENCORI revealing Hippo signaling and EMT-related genes likely to be regulated. Thus, their expression was analyzed by multiplexed qRT-PCR after miR-375 knockdown demonstrating only a limited change in expression. In summary, highly effective miR-375 knockdown in classical MCC cell lines did neither significantly change cell viability, morphology, nor oncogenic signaling pathways. These observations render miR-375 an unlikely intracellular oncogene in MCC cells, thus suggesting to address likely functions of miR-375 for intercellular communication of MCC.
Chlamydomonas sp. UWO241 exhibits constitutively high cyclic electron flow and rewired metabolism under high salinity
Authors: Kalra Isha , Wang Xin , Cvetkovska Marina , Jeong Jooyeon , McHargue William , Zhang Ru , Hüner Norman , Yuan Joshua S. , Morgan-Kiss Rachael 
Published: October 2019

ABSTRACTThe Antarctic green alga Chlamydomonas sp. UWO241 (UWO241) was isolated from the deep photic zone of a permanently Antarctic ice-covered lake. Adaptation to permanent low temperatures, hypersalinity, and extreme shade has resulted in survival strategies in this halotolerant psychrophile. One of the most striking phenotypes of UWO241 is an altered photosystem I (PSI) organization and constitutive PSI cyclic electron flow (CEF). To date, little attention has been paid to CEF during long-term stress acclimation and the consequences of sustained CEF in UWO241 are not known. In this study, we combined photobiology, proteomics, and metabolomics to understand the underlying role of sustained CEF in high salinity stress acclimation. High salt-grown UWO241 exhibited increased thylakoid proton motive flux and an increased capacity for NPQ. A Bestrophin-like Cl- channel was identified in the whole cell proteomes and transcriptome of UWO241 which likely supports ion homeostasis during high transthylakoid pH. Under high salt, a significant proportion of the upregulated enzymes were associated with the Calvin Benson Bassham Cycle (CBB), secondary metabolite biosynthesis, and protein translation. Two key enzymes of the Shikimate pathway, DAHP synthase and chorismate synthase, were also upregulated, as well as indole-3-glycerol phosphate synthase, an enzyme involved in biosynthesis of L-tryptophan and indole acetic acid. In addition, several compatible solutes (glycerol, proline and sucrose) accumulated to high levels in high salt-grown UWO241 cultures. We suggest that UWO241 maintains constitutively high CEF with associated PSI-cytb6f supercomplex to support robust growth and strong photosynthetic capacity under a constant growth regime of low temperatures and high salinity.