bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospitalization Trends for Acute Kidney Injury in Kidney Transplant Recipients in the United States, 2004–2014
Authors: Garg Neetika , Kumar Nilay , Singh Tripti , Parajuli Sandesh , Astor Brad C. , Mandelbrot Didier , Djamali Arjang 
Published: February 2019

Background.
The incidence of acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) in the general population is increasing. However, there is limited information on the epidemiology of AKI-related hospitalizations in the prevalent US kidney transplant population.

Methods.
We analyzed trends in the incidence of hospitalizations with primary diagnosis of AKI and secondary diagnosis of AKI and AKI-D using data from the National Inpatient Sample 2004–2014. Co-primary endpoints were in-hospital mortality, length of stay (LOS), and cost. Survey analysis techniques were used to compute national estimates. Linear trends in outcomes were evaluated using linear regression.

Results.
There were a total of 37 562 hospitalizations for primary AKI, 136 628 for secondary AKI, and 10 731 for AKI-D during the study period. We found an increase in hospitalizations for all 3 diagnoses over time (13.7–24.7 per thousand kidney transplant recipients [KTRs] for primary AKI, 37.4–108.0 per thousand KTRs for secondary AKI, and 4.2–6.0 per thousand KTRs for AKI-D; all P trend < 0.01). This was accompanied by significant improvements in in-hospital mortality (3.2%–0.5% for primary and 6.1%–4.4% for secondary AKI; both P trend < 0.01), average LOS (5.3–4.6 days for primary and 8.4–7.2 days for secondary AKI; both P trend < 0.001), and cost ($11 635–$8234 for primary and $21 373–$17 470 for secondary AKI; P trend < 0.001 for both).

Conclusions.
The incidence of hospitalizations for AKI and AKI-D among KTRs is rapidly rising. This has been accompanied by significant improvements in in-hospital mortality, LOS, and cost.
Twenty-year Follow-up of Histocompatibility Leukocyte Antigen-matched Kidney and Bone Marrow Cotransplantation for Multiple Myeloma With End-stage Renal Disease: Lessons Learned
Authors: Spitzer Thomas R. , Tolkoff-Rubin Nina , Cosimi A. Benedict , McAfee Steven , Dey Bimalangshu R. , Chen Yi-Bin , Delmonico Francis , Sykes Megan , Sachs David H. , Kawai Tatsuo 
Published: February 2019

Background.
Specific immune tolerance of transplanted organs in association with either transient or sustained lymphohematopoietic chimerism has been demonstrated in several preclinical animal models and clinically in patients who are full donor chimeras after hematopoietic stem cell transplantation and subsequently received kidney transplants from the same donor. Most recently, tolerance induction has been extended to patients in whom chimerism was intentionally induced at the time of kidney transplantation.

Methods.
Twenty years ago, we reported the first successful histocompatibility leukocyte antigen-matched sibling donor bone marrow and kidney transplant following nonmyeloablative conditioning in a patient with multiple myeloma and end-stage renal disease (ESRD). After 2 decades, she has normal renal function in the absence of ongoing systemic immunosuppressive therapy. Nine patients have subsequently undergone similar treatment for multiple myeloma with ESRD.

Results.
In the initial patient, hematopoietic chimerism was detectable for only 105 days after the transplant. In subsequent patients, chimerism detection ranged from 49 days to >14 years. Nevertheless, a long remission of the myeloma and long-term immunosuppression-free survival of the kidney allograft were achieved in 7 of the 10 patients, 5 of whom currently survive.

Conclusions.
This initial patient demonstrated the feasibility of performing combined histocompatibility leukocyte antigen-matched, sibling donor bone marrow and kidney transplantation for ESRD due to multiple myeloma. This experience paved the way for extending the initial trial to 9 additional patients with multiple myeloma and ESRD and, more recently, to tolerance induction strategies involving combined bone marrow and kidney transplantation for patients with and without an underlying malignancy.
The Association of 25-Hydroxyvitamin D Levels with Late Cytomegalovirus Infection in Kidney Transplant Recipients: the Wisconsin Allograft Recipient Database
Authors: Astor Brad C. , Djamali Arjang , Mandelbrot Didier A. , Parajuli Sandesh , Melamed Michal L. 
Published: February 2019

Background.
Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in kidney transplant recipients. Vitamin D has an integral role in proper immune function, and deficiency is common among kidney transplant recipients. It remains unclear whether 25-hydroxyvitamin D [25(OH)D] level is associated with CMV infection in kidney transplant recipients.

Methods.
We examined the relationship between 25(OH)D levels, measured at least 6 months posttransplant, and subsequent CMV infection in 1976 recipients free of prior CMV infection.

Results.
Of 1976 recipients, 251 (12.7%) were vitamin D deficient [25(OH)D <20 ng/mL] and 548 (27.7%) were insufficient (20–29 ng/mL) at the time of the first 25(OH)D measurement. A total of 107 recipients had a CMV infection within 1 year of a 25(OH)D measurement. Vitamin D deficiency was associated with a 1.81-fold higher risk (relative hazard = 1.81; 95% confidence interval [CI], 1.06-3.09) than vitamin D sufficiency after adjustment for baseline characteristics and concurrent graft function and blood calcineurin inhibitor concentration. Each 1 ng/mL lower 25(OH)D was associated with a 2% higher risk of infection (95% CI, 0%-4%) in continuous analyses after adjustment.

Conclusions.
Low 25(OH)D is common in kidney transplant recipients and associated with late CMV infection. These results highlight the need for interventional trials to assess the potential for vitamin D supplementation to reduce infectious complications in kidney transplant recipients.
A Recipient Risk Prediction Tool for Short-term Mortality After Pediatric Heart Transplantation
Authors: Choudhry Swati , Wang Yunfei , Denfield Susan W. , Cabrera Antonio G. , Price Jack F. , Tunuguntla Hari P. , Dharnidharka Vikas R. , Canter Charles E. , Dreyer William J. 
Published: February 2019

Background.
The first year after heart transplantation (HT) has the highest risk of mortality. We aim to derive and validate a recipient risk prediction tool for early mortality after pediatric HT.

Methods.
The International Society for Heart and Lung Transplantation (ISHLT) registry was used to identify patients (≤18 y) who underwent primary HT during January 2000–December 2014. Independent predictors of 1-year mortality were identified based on recipient characteristics at HT. Risk scores were assigned based on the magnitude of relative odds of 1-year mortality. The predictive capability of the ISHLT registry derived recipient risk score was externally validated using the Scientific Registry of Transplant Recipients registry data from 2015 to 2017 to ensure a cohort of patients completely exclusive from the derivation cohort.

Results.
A total of 5045 eligible patients were included in the analysis. The 20-point risk scoring system incorporated 8 recipient variables, including age at HT, diagnosis, pre-HT ventilator use, extracorporeal membrane oxygenation, inhaled nitric oxide use, infection, estimated glomerular filtration rate, and serum bilirubin. Compared with low-risk score group, high-risk group had 7-fold increased risk of 1-year mortality (hazard ratio 7.4; 95% CI [5.2-9.1]; P < 0.001). The C-statistics (0.77) and Hosmer-Lemeshow goodness of fit (0.9) for recipient risk score using derivation cohort from ISHLT registry performed well and was similar to the internal and external validation cohort (C-statistics 0.75, 0.78 and Hosmer-Lemeshow goodness of fit P = 0.4, 0.3, respectively).

Conclusions.
This study derived and externally validated a simple risk predictive model based on recipient characteristics at HT that has good prediction characteristics for 1-year post-HT mortality. This model may help clinicians identify candidates who are at a higher risk for post-HT mortality and may optimize organ sharing.
Global & Temporal Patterns of Submicroscopic Plasmodium falciparum Malaria Infection
Authors: Whittaker Charles , Slater Hannah , Bousema Teun , Drakeley Chris , Ghani Azra , Okell Lucy 
Published: February 2019

AbstractMolecular detection of Plasmodium falciparum infection has revealed large numbers of individuals with low-density (yet transmissible) infections undetectable by microscopy. Here we present an updated systematic review of cross-sectional malaria surveys to explore the prevalence and drivers of these submicroscopic infections and define where they are likely to be relevant to malaria control efforts. Our results show that submicroscopic infections predominate in low transmission settings, but also reveal marked geographical variation in their prevalence, being highest in South American surveys and lowest in West African studies. Whilst current transmission levels partly explain these results, we find that historical transmission intensity also represents a crucial determinant of the size of the submicroscopic reservoir. Submicroscopic infection was more likely in adults than children, although we did not observe a statistically significant influence of seasonality. Our results suggest that the contribution of submicroscopic infections to transmission likely varies substantially across settings, potentially warranting different approaches to their targeting in the approach to elimination.
Density-dependent natural selection mediates harvest-induced trait changes
Authors: Bouffet-Halle Alix , Mériguet Jacques , Carmignac David , Agostini Simon , Millot Alexis , Perret Samuel , Motard Eric , Decenciere Beatriz , Edeline Eric 
Published: February 2019

ABSTRACTRapid life-history changes caused by size-selective harvesting are often interpreted as a response to direct harvest selection against a large body size. However, similar trait changes may result from a harvest-induced relaxation of natural selection for a large body size via density-dependent selection. Here, we show evidence of such density-dependent selection favouring large-bodied individuals at high population densities, in replicated pond populations of medaka fish. Harvesting, in contrast, selected medaka directly against large-bodied medaka and, in parallel, decreased medaka population densities. Five years of harvesting were enough for harvested and unharvested medaka populations to inherit the classically-predicted trait differences, whereby harvested medaka grew slower and matured earlier than unharvested medaka. We demonstrate that this life-history divergence was not driven by direct harvest selection for a smaller body size in harvested populations, but by density-dependent natural selection for a larger body size in unharvested populations.
Human CST suppresses origin licensing and promotes AND-1/Ctf4 chromatin association
Authors: Wang Yilin , Brady Kathryn S. , Caiello Benjamin , Ackerson Stephanie M. , Stewart Jason A. 
Published: February 2019

AbstractHuman CTC1-STN1-TEN1 (CST) is an RPA-like single-stranded DNA binding protein that interacts with DNA polymerase α-primase (pol α) and functions in telomere replication. Previous studies suggest that CST also promotes replication restart following fork stalling. However, the precise role of CST in genome-wide replication remains unclear. In this study, we sought to understand whether CST alters origin licensing and activation. Replication origins are licensed by loading of the minichromosome maintenance 2-7 (MCM) complex in G1 followed by replisome assembly and origin firing in S-phase. We find that CST directly interacts with the MCM complex and disrupts binding of CDT1 to MCM, leading to decreased origin licensing. We also show that CST enhances replisome assembly by promoting AND-1/pol α chromatin association. Moreover, these interactions are not dependent on exogenous replication stress, suggesting that CST acts as a specialized replication factor during normal replication. Overall, our findings implicate CST as a novel regulator of origin licensing and replisome assembly/fork progression through interactions with MCM, AND-1 and pol α.
An ambiguous N-terminus drives the dual targeting of an antioxidant protein Thioredoxin peroxidase (TgTPx1/2) to endosymbiotic organelles inToxoplasma gondii
Authors: Mastud Pragati , Patankar Swati 
Published: February 2019

AbstractToxoplasma gondiiharbors two endosymbiotic organelles: a relict plastid, the apicoplast and a mitochondrion. The parasite expresses an antioxidant protein, thioredoxin peroxidase 1/2 (TgTPx1/2), that is dually targeted to these organelles. Nuclear-encoded proteins such as TgTPx1/2 are trafficked to the apicoplast via a secretory route through the endoplasmic reticulum (ER) and to the mitochondrion via a non-secretory pathway comprising of translocon uptake. Given the two distinct trafficking pathways for localization to the two organelles, the signals in TgTPx1/2 for this dual targeting are open areas of investigation. Here we show that the signals for apicoplast and mitochondrial trafficking lie in the N-terminal 50 amino acids of the protein and are overlapping. Interestingly, mutational analysis of the overlapping stretch shows that despite this overlap, the signals for individual organellar uptake can be easily separated. Further, deletions in the N-terminus also reveal a 10 amino acid stretch that is responsible for targeting the protein from punctate structures surrounding the apicoplast into the organelle itself. Collectively, results presented in this report suggest that an ambiguous signal sequence for organellar uptake combined with a hierarchy of recognition by the protein trafficking machinery drives the dual targeting of TgTPx1/2.
The Hsp70/Hsp90 Co-Chaperone Hop/Stip1 Shifts the Proteostatic Balance from Folding Towards Degradation
Authors: Bhattacharya Kaushik , Weidenauer Lorenz , Morán Luengo Tania , Echeverría Pablo C. , Bernasconi Lilia , Wider Diana , Villemin Matthieu , Bauer Christoph , Rüdiger Stefan G. D. , Quadroni Manfredo , Picard Didier 
Published: February 2019

SUMMARYHop/Stip1/Sti1 is thought to be essential as a co-chaperone to facilitate substrate transfer between the Hsp70 and Hsp90 molecular chaperones. Despite this proposed key function for protein folding and maturation, it is not essential in a number of eukaryotes and bacteria lack an ortholog. We set out to identify and to characterize its eukaryote-specific function. Human cell lines and the budding yeast with deletions of the Hop/Sti1 gene display reduced proteasome activity due to inefficient capping of the core particle with regulatory particles. Unexpectedly, knock-out cells are more proficient at preventing protein aggregation and at promoting protein refolding. Without the restraint by Hop, a more efficient folding activity of the prokaryote-like Hsp70/Hsp90 complex, which can also be demonstrated in vitro, compensates for the proteasomal defect and ensures an alternate proteostatic equilibrium. Thus, cells may act on Hop to shift the proteostatic balance between folding and degradation.
A 96-well culture platform enables longitudinal analyses of engineered human skeletal muscle microtissue strength
Authors: Afshar Mohammad E. , Abraha Haben Y. , Bakooshli Mohsen A. , Davoudi Sadegh , Thavandiran Nimalan , Tung Kayee , Ahn Henry , Ginsberg Howard , Zandstra Peter W. , Gilbert Penney M. 
Published: February 2019

ABSTRACTThree-dimensional (3D) in vitro models of human skeletal muscle mimic aspects of native tissue structure and function, thereby providing a promising system for disease modeling, drug discovery or pre-clinical validation, and toxicity testing. Widespread adoption of this research approach is hindered by the lack of an easy-to-use platform that is simple to fabricate and yields arrays of human skeletal muscle micro-tissues (hMMTs) in culture with reproducible physiological responses that can be assayed non-invasively. Here, we describe a design and methods to generate a reusable mold to fabricate a 96-well platform, referred to as MyoTACTIC, that enables bulk production of 3D hMMTs. All 96-wells and all well features are cast in a single step from the reusable mold. Non-invasive calcium transient and contractile force measurements are performed on hMMTs directly in MyoTACTIC, and unbiased force analysis occurs by a custom automated algorithm, allowing for longitudinal studies of function. Characterizations of MyoTACTIC and resulting hMMTs confirms the reproducibility of device fabrication and biological responses. We show that hMMT contractile force mirrors expected responses to compounds shown by others to decrease (dexamethasone, cerivistatin) or increase (IGF-1) skeletal muscle strength. Since MyoTACTIC supports hMMT long-term culture, we evaluated direct influences of pancreatic cancer chemotherapeutics agents on contraction competent human skeletal muscle fibers. A single application of a clinically relevant dose of Irinotecan decreased hMMT contractile force generation, while clear effects on fiber atrophy were observed histologically only at a higher dose. This suggests an off-target effect that may contribute to cancer associated muscle wasting, and highlights the value of the MyoTACTIC platform to non-invasively predict modulators of human skeletal muscle function.
High-density spatial transcriptomics arrays for in situ tissue profiling
Authors: Vickovic Sanja , Eraslan Gökcen , Klughammer Johanna , Stenbeck Linnea , Salmén Fredrik , Äijö Tarmo , Bonneau Richard , Bergenstråhle Ludvig , Gould Joshua , Ronaghi Mostafa , Frisén Jonas , Lundeberg Joakim , Regev Aviv , Ståhl Patrik L 
Published: February 2019

AbstractTissue function relies on the precise spatial organization of cells characterized by distinct molecular profiles. Single-cell RNA-Seq captures molecular profiles but not spatial organization. Conversely, spatial profiling assays either lack global transcriptome information or are not at the single-cell level. Here, we develop High-Density Spatial Transcriptomics (HDST), a method for RNA-seq at high spatial resolution. Spatially barcoded reverse transcription oligonucleotides are coupled to beads that are then randomly deposited in individual wells on a slide. The barcoded beads are decoded and coupled to a specific spatial address. We then capture and spatially in situ label RNA from the same histological tissue sections placed on the bead array slide. HDST recovers hundreds of thousands of transcript-coupled barcodes per experiment at 2 μm resolution. We demonstrate HDST in the mouse brain, use it to resolve spatial expression patterns and cell types, and show how to combine it with histological stains to relate expression patterns to tissue architecture and anatomy. HDST opens the way to 2D spatial analysis of tissues at high resolution.
Autistic women’s experience of intimate relationships: the impact of an adult diagnosis
Authors: Kock Elizabeth , Strydom Andre , O’Brady Deirdre , Tantam Digby 
Published: February 2019

Purpose
The purpose of this paper is to explore the experience of intimate relationships of women who have been diagnosed with Autism in adulthood.

Design/methodology/approach
Semi-structured interviews were used to interview eight participants. The data were transcribed and analysed using the interpretative phenomenological analysis method.

Findings
Four overall themes were identified. These included “Response to the diagnosis and receiving more information about Autism”, “Factors influencing dating behaviour”, “Sex and sexual experiences” and “Experience of intimate relationships as a person with Autism”.

Research limitations/implications
The results of this study have implications for both research and clinical practice as it highlights the areas in which women newly diagnosed with autism spectrum disorder (ASD) could benefit from support.

Practical implications
The study hopes to add to the limited existing research on adult women with ASD.

Originality/value
To date no similar research has investigated the same phenomenon through a similar method.
Journey to diagnosis for women with autism
Authors: Zener Dori 
Published: February 2019

PurposeThe purpose of this paper is to review the barriers that girls and women face in receiving an accurate and timely autism diagnosis. The journey to late-in-life diagnosis will be explored with a focus on mental health and well-being. The aim is to improve the awareness of the female autism phenotype to provide access to early identification and appropriate supports and services.Design/methodology/approachThe author’s clinical experience as an individual, couple and family therapist specializing in girls and women with autism informs the paper. Research on co-occurring mental health experience and diagnoses are reviewed and combined with case examples to outline the themes leading to and obscuring autism diagnosis.FindingsFemales with autism are less likely to be diagnosed or are identified much later than their male counterparts. Living with unidentified autism places significant mental strain on adults, particularly females. Achieving a late-in-life diagnosis is very valuable for adults and can improve self-awareness and access to limited support.Practical implicationsMental health professionals will develop a better understanding of the overlap between autism and psychiatric conditions and should consider autism in females who are seeking intervention.Originality/valueThis paper provides a clinical approach to working with autistic girls and women. This knowledge can complement the existing research literature and help build the foundation for a greater understanding of the female autism phenotype.
The impact of customer orientation on the quantity and quality of user-generated content
Authors: Yoo Bosul , Katsumata Sotaro , Ichikohji Takeyasu 
Published: February 2019

Purpose
The purpose of this paper is to examine the driving factors of user innovation behaviors using the case of smartphone applications to estimate the indirect and direct effects of consumers’ attitudes toward user-generated content (UGC).

Design/methodology/approach
This study proposes a structural model to examine the relationship between user innovation behaviors toward UGC and three attitude factors: involvement, consumer knowledge and customer orientation. The empirical analysis is based on a consumer survey that examines the commonalities and differences between Japan and China. In each country, two social media services are chosen as representative cases of the UGC business model to measure user innovation behaviors toward the quality and quantity aspects.

Findings
Customer orientation is the most significant driving factor of user innovation behaviors toward UGC. It positively affects both the number of followers and the frequency of information transmissions. In particular, for the quality dimension of user innovation, customer orientation has a more significant effect on the number of followers than does familiarity.

Originality/value
This study emphasizes the quality aspect of user innovation. Previous research has focused on the quantity of user innovation behaviors by measuring the amount of information. However, this research measures both the quality and the quantity aspects with the number of followers and the frequency of uploading content. The findings of this study suggest that companies should maintain relationships with highly customer-oriented users to manage content quality.