bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulated Volume-Based Regionalization of Complex Procedures
Authors: Fong Zhi Ven , Hashimoto Daniel A. , Jin Ginger , Haynes Alex B. , Perez Numa , Qadan Motaz , Ferrone Cristina R. , Fernandez-del Castillo Carlos , Warshaw Andrew L. , Lillemoe Keith D. , Traeger Lara N. , Chang David C. 
Published: August 2019

Objective:
This study simulates the regionalization of pancreatectomies to assess its impact on spatial access in terms of patient driving times.

Background:
Although policies to regionalize complex procedures to high-volume centers may improve outcomes, the impact on patient access is unknown.

Methods:
Patients who underwent pancreatectomies from 2005 to 2014 were identified from California's statewide database. Round-trip driving times between patients’ home ZIP code and hospital addresses were calculated via Google Maps. Regionalization was simulated by eliminating hospitals performing <20 pancreatectomies/yr, and reassigning patients to the next closest hospital that satisfied the volume threshold. Sensitivity analyses were performed for New York and Medicare patients to assess for influence of geography and insurance coverage, respectively.

Results:
Of 13,317 pancreatectomies, 6335 (47.6%) were performed by hospitals with <20 cases/yr. Patients traveled a median of 49.8 minutes [interquartile range (IQR) 30.8–96.2] per round-trip. A volume-restriction policy would increase median round-trip driving time by 24.1 minutes (IQR 4.5–53.5). Population in-hospital mortality rates were estimated to decrease from 6.7% to 2.8% (P < 0.001). Affected patients were more likely to be racial minorities (44.6% vs 36.5% of unaffected group, P < 0.001) and covered by Medicaid or uninsured (16.3% vs 9.8% of unaffected group, P < 0.001). Sensitivity analyses revealed a 17.8 minutes increment for patients in NY (IQR 0.8–47.4), and 27.0 minutes increment for Medicare patients (IQR 6.2–57.1).

Conclusions:
A policy that limits access to low-volume pancreatectomy hospitals will increase round-trip driving time by 24 minutes, but up to 54 minutes for 25% of patients. Population mortality rates may improve by 1.5%.
AntagomiR-199a Enhances the Liver Protective Effect of Hypoxia-Preconditioned BM-MSCs in a Rat Model of Reduced-Size Liver Transplantation
Authors: Zhang Weichen , Chen Qi , Ye Yufu , Zou Bei , Liu Yuanxing , Cheng Longyu , Yu Jun , Zheng Shusen 
Published: August 2019

Background.
Reduced-size liver transplantation (LT) was invented to overcome the shortage of donor livers; however, it has proven to be more susceptible to ischemia-reperfusion injury. Bone marrow-derived mesenchymal stem cell infusion has been shown to be protective following LT. Optimization of MSC infusion has been performed, among which hypoxia preconditioning and miRNA modulation have shown promise. MiR-199a inhibition was reported to induce angioneogenesis; however, whether mir-199a inhibition enhances the protective effect of Bone marrow-derived mesenchymal stem cells in LT remains unknown. In this study, we combined antagomiR-199a with hypoxia-preconditioned MSC (H-MSC) infusion to discuss their effect and mechanism in a rat model of reduced-size LT.

Methods.
A reduced-size LT model was constructed and H-MSCs were intraportally injected during operation. AgomiR-199a and antagomir-199a were injected through the caudal vein once a day after LT. The level of apoptosis and proinflammatory cytokines were measured. An anti-vascular endothelial growth factor (VEGF) antibody was injected to further explore the underlying mechanism.

Results.
AntagomiR-199a plus H-MSC not only significantly decreased ALT and AST 72 h after LT but also ameliorated the level of apoptosis and inhibited inflammatory reactions. On the contrary, agomir-199a reduced the protective effect of the H-MSC infusion. In terms of mechanism, the liver protective effect of miR-199a inhibition was abolished by treatment with a VEGF-neutralizing antibody.

Conclusions.
AntagomiR-199a enhanced the protective effect of H-MSCs infusion via activation of the hypoxia induction factor 1α/VEGF axis.
Recipient Comorbidity and Survival Outcomes After Kidney Transplantation: A UK-wide Prospective Cohort Study
Authors: Wu Diana A. , Robb Matthew L. , Forsythe John L.R. , Bradley Clare , Cairns John , Draper Heather , Dudley Christopher , Johnson Rachel J. , Metcalfe Wendy , Ravanan Rommel , Roderick Paul , Tomson Charles R.V. , Watson Christopher J.E. , Bradley J. Andrew , Oniscu Gabriel C. 
Published: August 2019

Background.
Comorbidity is increasingly common in kidney transplant recipients, yet the implications for transplant outcomes are not fully understood. We analyzed the relationship between recipient comorbidity and survival outcomes in a UK-wide prospective cohort study—Access to Transplantation and Transplant Outcome Measures (ATTOM).

Methods.
A total of 2100 adult kidney transplant recipients were recruited from all 23 UK transplant centers between 2011 and 2013. Data on 15 comorbidities were collected at the time of transplantation. Multivariable Cox regression models were used to analyze the relationship between comorbidity and 2-year graft survival, patient survival, and transplant survival (earliest of graft failure or patient death) for deceased-donor kidney transplant (DDKT) recipients (n = 1288) and living-donor kidney transplant (LDKT) recipients (n = 812).

Results.
For DDKT recipients, peripheral vascular disease (hazard ratio [HR] 3.04, 95% confidence interval [CI]: 1.37-6.74; P = 0.006) and obesity (HR 2.27, 95% CI: 1.27-4.06; P = 0.006) were independent risk factors for graft loss, while heart failure (HR 3.77, 95% CI: 1.79-7.95; P = 0.0005), cerebrovascular disease (HR 3.45, 95% CI: 1.72-6.92; P = 0.0005), and chronic liver disease (HR 4.36, 95% CI: 1.29-14.71; P = 0.018) were associated with an increased risk of mortality. For LDKT recipients, heart failure (HR 3.83, 95% CI: 1.15-12.81; P = 0.029) and diabetes (HR 2.23, 95% CI: 1.03-4.81; P = 0.042) were associated with poorer transplant survival.

Conclusions.
The key comorbidities that predict poorer 2-year survival outcomes after kidney transplantation have been identified in this large prospective cohort study. The findings will facilitate assessment of individual patient risks and evidence-based decision making.
Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated Donor Using Tacrolimus/Sirolimus-based GvHD Prophylaxis: Impact of HLA Mismatch
Authors: Al Malki Monzr M. , Gendzekhadze Ketevan , Yang Dongyun , Mokhtari Sally , Parker Pablo , Karanes Chatchada , Palmer Joycelynne , Snyder David , Forman Stephen J. , Nademanee Auayporn , Nakamura Ryotaro 
Published: August 2019

Background.
While tacrolimus and sirolimus (T/S)-based graft-versus-host disease (GvHD) prophylaxis has been effective in preventing acute GvHD post hematopoietic cell transplantation (HCT), its efficacy and long-term outcome in matched (MUD) and mismatched unrelated donor (mMUD) setting is not well defined.

Methods.
Herein, we evaluated a consecutive case-series of 482 patients who underwent unrelated donor HCT (2005–2013) with T/S-based GvHD prophylaxis.

Results.
With a median follow-up of 6.2 years (range = 2.4–11.3), the 5-year overall survival (OS) and relapse/progression-free survival were 47.5% (95% confidence interval [CI]: 43.0-52.0) and 43.6% (95% CI: 39.1-48.1), respectively; and the 5-year cumulative incidence of nonrelapse mortality (NRM) and relapse were 24.9%, and 31.5%, respectively. In this cohort, mMUD was associated with worse OS (39.0% versus 50.7% at 5 y; P = 0.034), primarily due to greater risk of NRM (33.5% versus 21.7%; P = 0.038). While rates of relapse, acute (II–IV or III–IV) or chronic GvHD (limited or extensive) were not different, death caused by chronic GvHD (20.8% versus 12.8%; P = 0.022) and infection (33.0% versus 18.1%; P < 0.01) were significantly greater in mMUD. In multivariable analysis, high-risk disease (hazard ratio [HR] = 2.21, 95% CI: 1.16-4.23; P < 0.01) and mMUD (HR = 1.55, 95% CI: 1.15-2.08; P = 0.004) were independent predictive factors for OS.

Conclusions.
T/S-based GvHD prophylaxis is an effective and acceptable GvHD prophylactic regimen. However, survival after mMUD remained poor, possibly related to the severity of chronic GvHD.
The relevance of dominance and functional annotations to predict agronomic traits in hybrid maize
Authors: Ramstein Guillaume P. , Larsson Sara J. , Cook Jason P. , Edwards Jode W. , Ersoz Elhan S. , Flint-Garcia Sherry , Gardner Candice A. , Holland James B. , Lorenz Aaron J. , McMullen Michael D. , Millard Mark J. , Rocheford Torbert R. , Tuinstra Mitchell R. , Bradbury Peter J. , Buckler Edward S. , Romay M. Cinta 
Published: August 2019

ABSTRACTHeterosis has been key to the development of maize breeding but describing its genetic basis has been challenging. Previous studies of heterosis have shown the contribution of within-locus complementation effects (dominance) and their differential importance across genomic regions. However, they have generally considered panels of limited genetic diversity and have shown little benefit to including dominance effects for predicting genotypic value in breeding populations. This study examined within-locus complementation and enrichment of genetic effects by functional classes in maize. We based our analyses on a diverse panel of inbred lines crossed with two testers representative of the major heterotic groups in the United States (1,106 hybrids), as well as a collection of 24 biparental populations crossed with a single tester (1,640 hybrids). We assayed three agronomic traits: days to silking (DTS), plant height (PH) and grain yield (GY). Our results point to the presence of dominance for all traits, but also among-locus complementation (epistasis) for DTS and genotype-by-environment interactions for GY. Consistently, dominance improved genomic prediction for PH only. In addition, we assessed enrichment of genetic effects in classes defined by genic regions (gene annotation), structural features (recombination rate and chromatin openness), and evolutionary features (minor allele frequency and evolutionary constraint). We found support for enrichment in genic regions and subsequent improvement of genomic prediction for all traits. Our results point to mechanisms by which heterosis arises through local complementation in proximal gene regions and suggest the relevance of dominance and gene annotations for genomic prediction in maize.
Spectral and lifetime fluorescence unmixing via deep learning
Authors: Smith Jason T. , Ochoa Marien , Intes Xavier R. M. 
Published: August 2019

AbstractHyperspectral Fluorescence Lifetime Imaging allows for the simultaneous acquisition of spectrally resolved temporal fluorescence emission decays. In turn, the acquired rich multidimensional data set enables simultaneous imaging of multiple fluorescent species for a comprehensive molecular assessment of biotissues. However, to enable quantitative imaging, inherent spectral overlap between the considered fluorescent probes and potential bleed-through must be taken into account. Such task is performed via either spectral or lifetime unmixing, typically independently. Herein, we present UNMIX-ME (unmix multiple emissions), a deep learning-based fluorescence unmixing routine, capable of quantitative fluorophore unmixing by simultaneously using both spectral and temporal signatures. UNMIX-ME was trained and validated using anin silicoframework replicating the data acquisition process of a compressive hyperspectral fluorescent lifetime imaging platform (HMFLI). It was benchmarked against a conventional LSQ method for both tri and quadri-exponential simulated samples. Last, UNMIX-ME’s potential was assessed for NIR FRETin vitroandin vivofor small animal experimental data.
Dynamic response of RNA editing to temperature in Grape by RNA deep-sequencing
Authors: Zhang Aidi , Jiang Xiaohan , Zhang Fuping , Wang Tengfei , Zhang Xiujun 
Published: August 2019

AbstractRNA editing is a post-transcriptional process of modifying genetic information on RNA molecules, which provides cells an additional level of gene expression regulation. Unlike mammals, in land plants, RNA editing converts C to U residues in organelles. However, its potential role in response to different stressors (heat, salt and so on) remains unclear. Grape is one of the most popular and economically important fruits in the world, and its production, like other crops, must deal with abiotic and biotic stresses, which cause reductions in yield and fruit quality. In our study, we tested the influence of the environmental factor temperature on RNA processing in the whole mRNA from grape organelle. In total, we identified 123 and 628 RNA editing in chloroplast and mitochondria respectively with the average editing extent nearly ~60%. The analyses revealed that number of non-synonymous editing sites were higher than that of synonymous editing sites, and the amino acid substitution type tend to be hydrophobic. Additionally, the overall editing level decreased with the temperature rises, especially several gene transcripts in chloroplast and mitochondria (matK, ndhB etc.). 245 sites were furthermore determined as stress-responsive sites candidates. We also found that the expression level of PPR genes decreased with the temperature rises, which may contribute to the loss of RNA editing at high temperature. Our findings suggest that the RNA editing events are very sensitive to high temperature, the changes of amino acid in these genes may contribute to the stress adaption for grape.
Descent of Bacteria and Eukarya from an archaeal root of life
Authors: Long Xi , Xue Hong , Wong J. Tze-Fei 
Published: August 2019

AbstractThe three biological domains delineated based on SSU rRNAs are confronted by uncertainties regarding the relationship between Archaea and Bacteria, and the origin of Eukarya. Herein the homologies between the paralogous valyl-tRNA and isoleucyl-tRNA synthetases in a wide spectrum of species revealed vertical gene transmission from an archaeal root of life through a Primitive Archaea Cluster to an Ancestral Bacteria Cluster of species. The higher homologies of the ribosomal proteins (rProts) of eukaryotic Giardia toward archaeal relative to bacterial rProts established that an archaeal-parent rather than a bacterial-parent underwent genome merger with an alphaproteobacterium to generate Eukarya. Moreover, based on the top-ranked homology of the proteins of Aciduliprofundum among archaea toward the Giardia and Trichomonas proteomes and the pyruvate phosphate dikinase of Giardia, together with their active acquisition of exogenous bacterial genes plausibly through foodchain gene adoption, the Aciduliprofundum archaea were identified as leading candidates for the archaeal-parent of Eukarya.
Application of non-invasive low-intensity pulsed electric field with thermal cycling-hyperthermia for synergistically enhanced anticancer effect of chlorogenic acid on PANC-1 cells
Authors: Lu Chueh-Hsuan , Kuo Yu-Yi , Lin Guan-Bo , Chen Wei-Ting , Chao Chih-Yu 
Published: August 2019

AbstractMost existing cancer treatments involve high-cost chemotherapy and radiotherapy, with major side effects, prompting effort to develop alternative treatment modalities. In this study, we propose a novel non-invasive treatment calling for exposure of cells to CGA, coupled with thermal-cycling hyperthermia (TC-HT) and low-intensity pulsed electric field (LIPEF). The study finds that this triple combination can significantly impede the proliferation of human pancreatic cancer PANC-1 cells, with only about 20% viable cells left after 24h, whereas being non-toxic to normal cells. The synergistic activity against the PANC-1 cells was achieved by inducing G2/M phase arrest and apoptosis, which were associated with up-regulation of p53 and coupled with increased expression of downstream proteins p21 and Bax. Further mechanism investigations revealed that the cytotoxic activity could be related to mitochondrial apoptosis, characterized by the reduced level of Bcl-2, mitochondrial dysfunction, and sequential activation of caspase-9 and PARP. Also, we found that the triple treatment led to the increase of intracellular reactive oxygen species (ROS) production. Notably, the triple treatment-induced cytotoxic effects and the elevated expression of p53 and p21 proteins as well as the increased Bax/Bcl-2 ratio, all could be alleviated by the ROS scavenger, N-acetyl-cysteine (NAC). These findings indicate that the combination of CGA, TC-HT, and LIPEF may be a promising modality for cancer treatment, as it can induce p53-dependent cell cycle arrest and apoptosis through accumulation of ROS in PANC-1 cells.
Genetic analyses reveal population structure and recent decline in leopards (Panthera pardus fusca) across Indian subcontinent
Authors: Bhatt Supriya , Biswas Suvankar , Karanth Krithi K. , Pandav Bivash , Mondol Samrat 
Published: August 2019

AbstractLarge carnivores maintain the stability and functioning of ecosystems. Currently, many carnivore species face declining population sizes due to natural and anthropogenic pressures. The leopard,Panthera pardus, is probably the most widely distributed and adaptable large carnivore, still persisting in most of its’ historic range. However, we lack subspecies level data on country or regional scale on population trends, as ecological monitoring approaches are difficult to apply on such wide-ranging species. We used genetic data from leopards sampled across the Indian subcontinent to investigate population structure and patterns of demographic decline. Our genetic analyses revealed four distinct subpopulations corresponding to Western Ghats, Deccan Plateau-Semi Arid, Shivalik and Terai region of north Indian landscapes, each with high genetic variation. Coalescent simulations with 13 microsatellite loci revealed a 75-90% population decline in between 120-200 years ago across India, possibly human induced. Population-specific estimates of genetic decline are in concordance with ecological estimates of local extinction probabilities in four sub-populations obtained from occupancy modelling of historic and current distribution of leopards in India. Our results confirm population decline of a widely distributed, adaptable large carnivore. We re-iterate the relevance of indirect genetic methods for such species, and recommend that detailed, landscape-level ecological studies on leopard populations are critical to future conservation efforts. Our approaches and inference are relevant to other widely distributed, seemingly unaffected carnivores such as the leopard.
Keeping patient phenotypes and genotypes private while seeking disease diagnoses
Authors: Jagadeesh Karthik A. , Wu David J. , Birgmeier Johannes A. , Boneh Dan , Bejerano Gill 
Published: August 2019

AbstractIn an age where commercial entities are allowed to collect and directly profit from large amounts of private information, an age where large data breaches of such organizations are discovered every month, science must strive to offer society viable ways to preserve privacy while benefitting from the power of data sharing. Patient phenotypes and genotypes are critical for building groups of phenotypically-similar patients, identify the gene that best explains their common phenotypes, and ultimately, diagnose a patient with a Mendelian disease. Direct computation over these quantities requires highly-sensitive patient data to be shared openly, compromising patient privacy and opening patients up for discrimination. Existing protocols focus on secure computation over genotype data and only address the final steps of the disease-diagnosis pipeline where phenotypically-similar patients have been identified. However, identifying such patients in a secure and private manner remains open. In this work, we develop secure protocols to maintain patient privacy while computing meaningful operations over both genotypic and phenotypic data for two real scenarios: COHORT DISCOVERY and GENE PRIORITIZATION. Our protocols newly enable a complete and secure end-to-end disease diagnosis pipeline that protects sensitive patient phenotypic and genotypic data.
Plant economic strategies of grassland species control soil carbon dynamics through rhizodeposition
Authors: Henneron Ludovic , Cros Camille , Picon‐Cochard Catherine , Rahimian Vida , Fontaine Sébastien 
Published: August 2019

Abstract

The plant economics spectrum is increasingly recognized as a major determinant of plant species effects on terrestrial ecosystem functioning related to carbon cycling. However, the role of plant economic strategies in the effects of living root activity on soil organic carbon (SOC) dynamics through rhizodeposition remains unexplored, despite SOC being the largest terrestrial carbon pool.

Using a continuous 13C‐labelling method allowing partitioning of plant and soil sources to carbon fluxes and pools, we studied here the linkages between plant economic strategies and SOC cycling processes in a ‘common garden’ greenhouse experiment. It includes a panel of 12 grassland species selected along a gradient of economic traits and belonging to three functionnal groups (C3 grasses, forbs and legumes).

All species induced an acceleration of native SOC mineralization but this rhizosphere priming effect (RPE) substantially differed across species and varied eleven‐fold by the end of the experiment (from +26% to +295% relative to unplanted soil). Interspecific variation in RPE was primarily linked to plant photosynthetic activity associated to species economic strategies of light and CO2 resource acquisition and processing. Fast‐growing acquisitive species, such as legumes, featured large RPE, in relation with their high canopy photosynthesis coupled to high leaf photosynthetic capacity and large net primary productivity allocated above‐ground. This large RPE was further associated with high root metabolic activity, rhizodeposition and soil microbial activity. In contrast, fine‐root growth and economic traits related to soil resource foraging ability were poor predictors of RPE.

The formation of new root‐derived SOC varied nine‐fold across species and was similarly positively related to the net primary productivity allocated above‐ground. Fast‐growing acquisitive species with a high photosynthetic activity induced a disproportionately large RPE relative to SOC formation.

Synthesis. Overall, our study demonstrates that rhizodeposition is a major mechanism through which plant economic strategies of grassland species control soil carbon dynamics. Acquisitive versus conservative species were associated with high versus low rates of photosynthesis and rhizodeposition, in turn leading to fast versus slow SOC turnover. This emphasizes the importance of considering rhizosphere processes for understanding plant species effects on soil biogeochemistry.