bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient Travel Distance and Post Lung Transplant Survival in the United States: A Cohort Study
Authors: Tsuang Wayne M. , Arrigain Susana , Lopez Rocio , Snair Megan , Budev Marie , Schold Jesse D. 
Published: January 2020

Background.
In response to a longstanding Federal mandate to minimize the role of geography in access to transplant in the United States, we assessed whether patient travel distance was associated with lung transplant outcomes. We focused on the posttransplant time period, when the majority of patient visits to a transplant center occur.

Methods.
We present a cohort study of lung transplants in the United States between January 1, 2006, and May 31, 2017. Travel distance was measured from the patient’s permanent home zip code to the transplant center using SAS URL access to GoogleMaps. We leveraged data from the US Census, US Department of Agriculture, and the Economic Innovations Group to assess socioeconomic status. Multivariable Cox models were used to assess graft survival.

Results.
We included 18 128 patients who met the inclusion criteria. Median distance was 69.6 miles. Among patients who traveled >60 miles to reach a transplant center, 41.8% bypassed a closer center and sought care at a more distant center. Patients traveling longer distances sought care at centers with a higher annual transplant volume. In the adjusted Cox Model, patients who traveled >360 miles had a slightly higher risk for posttransplant graft failure than patients traveling ≤60 miles (hazard ratio 1.09; 95% CI, 1.01-1.18), and a higher risk for treated acute rejection (hazard ratio, 1.63; 95% CI, 1.43-1.86).

Conclusions
Travel distance was significantly associated with post lung transplant survival. However, this effect was relatively modest. Patient travel distance is an important component of access to lung transplant care.
HOUSES Index as an Innovative Socioeconomic Measure Predicts Graft Failure Among Kidney Transplant Recipients
Authors: Stevens Maria A. , Beebe Timothy J. , Wi Chung-II , Taler Sandra J. , St. Sauver Jennifer L. , Juhn Young J. 
Published: January 2020

Background.
Despite extensive evaluation processes to determine candidacy for kidney transplantation, variability in graft failure exists. The role of patient socioeconomic status (SES) in transplantation outcomes is poorly understood because of limitations of conventional SES measures.

Methods.
This population-based retrospective cohort study assessed whether a validated objective and individual-level housing-based SES index (HOUSES) would serve as a predictive tool for graft failure in patients (n = 181) who received a kidney transplant in Olmsted County, MN (January 1, 1998 to December 8, 2016). Associations were assessed between HOUSES (quartiles: Q1 [lowest] to Q4 [highest]) and graft failure until last follow-up date (December 31, 2016) using Cox proportional hazards. The mean age (SD) was 46.1 (17.2) years, 109 (60.2%) were male, 113 (62.4%) received a living kidney donor transplant, and 40 (22.1%) had a graft failure event.

Results.
Compared with Q1, patients with higher HOUSES (Q2–Q4) had significantly lower graft failure rates (adjusted hazard ratio, 0.47; 95% confidence interval, 0.24-0.92; P < 0.029), controlling for age, sex, race, previous kidney transplantation, and donor type.

Conclusions.
Although criteria for kidney transplant recipients are selective, patients with higher HOUSES had lower graft failure rates. Thus, HOUSES may enable transplantation programs to identify a target group for improving kidney transplantation outcomes.
Comparing Emotional Adjustment of Living-donor and Deceased-donor Kidney Transplant Patients
Authors: Lai Yousheng Lester , Neo Hui Ling Michelle , Vathsala Anantharaman , Griva Konstadina 
Published: January 2020

Background.
Kidney transplantation is regarded as the best treatment option for patients with end-stage renal disease. However, living-donor recipients (LDRs) and deceased-donor recipients (DDRs) still face challenges in transplant-specific emotional adjustment post-transplantation. Research distinguishing emotional adjustment between transplant groups has been limited to Western settings, with little attention given to Asian populations. As such, documenting and comparing the emotional adjustment of LDRs and DDRs in an ethnically diverse Asian setting in Singapore and identifying factors associated with emotional adjustment are of interest.

Methods.
One hundred eighty-two kidney transplant patients (106 LDRs and 76 DDRs) completed measures of generic distress (Depression, Anxiety, Stress Scale-21) and transplantation-specific emotional and behavioral outcomes (Transplant Effects Questionnaire).

Results.
LDRs were significantly younger (P = 0.019) and had higher education levels (P = 0.007), higher personal income (P < 0.001), shorter dialysis vintage (P < .001), and higher estimated glomerular filtration rates (eGFRs) (P = 0.002) compared with DDRs. Generic symptoms of depression and stress were very low; however, 29.2% of LDRs and 19.7% of DDRs experienced moderate to severe symptoms of anxiety. Similarly, 83.0% of LDRs and 72.4% of DDRs reported high levels of transplant-specific worry. Multivariate models showed younger patients expressing greater generic distress, and transplant-specific worry (P < 0.01), despite higher eGFRs (P < 0.05). ANCOVA controlling for casemix differences showed that LDRs experienced higher feelings of guilt (P = 0.004) and greater willingness to disclosure (P = 0.041).

Conclusions.
Clinicians should be vigilant of younger kidney transplant patients who have greater risk of poorer emotional adjustment. Future interventions should target alleviating anxiety and transplant-specific worry.
Genomic alterations and abnormal expression of APE2 in multiple cancers
Authors: Jensen Katherine A. , Shi Xinghua , Yan Shan 
Published: January 2020

AbstractAlthough APE2 plays essential roles in base excision repair and ATR-Chk1 DNA damage response (DDR) pathways, it remains unknown how the APE2 gene is altered in the human genome and whether APE2 is differentially expressed in cancer patients. Here, we report multiple-cancer analyses of APE2 genomic alterations and mRNA expression from cancer patients using available data from The Cancer Genome Atlas (TCGA). We observe that APE2 genomic alterations occur at ~17% frequency in 14 cancer types (n= 21,769). Most frequent somatic mutations of APE2 appear in uterus (2.89%) and skin (2.47%) tumor samples. Furthermore, APE2 expression is upregulated in tumor tissue compared with matched non-malignant tissue across 5 cancer types including kidney, breast, lung, liver, and uterine cancers, but not in prostate cancer. We also examine the mRNA expression of 13 other DNA repair and DDR genes from matched samples for 6 cancer types. We show that APE2 mRNA expression is positively correlated with PCNA, APE1, XRCC1, PARP1, Chk1, and Chk2 across these 6 tumor tissue types; however, groupings of other DNA repair and DDR genes are correlated with APE2 with different patterns in different cancer types. Taken together, this study demonstrates alterations and abnormal expression of APE2 from multiple cancers.
Temporal Trends in Vaping Use: Demographic Diversity and Healthcare Utilization Outcomes
Authors: Nguyen Trevor , Nikova Teodora , Luong Eric , Bottling Patrick , Henglin Mir , Kim Elizabeth H. , Rader Florian , Danovitch Itai , Weinberg Aaron , Cheng Susan , Ebinger Joseph 
Published: January 2020

ABSTRACTBACKGROUNDUse of electronic cigarettes (e-cigarettes) has increased substantially in recent years. Marketed as a safer alternative to conventional tobacco cigarettes, the safety profile of e-cigarettes is now being questioned. Importantly, the clinical consequences of e-cigarette use remain poorly characterized.METHODSUsing data from the electronic health record (EHR), we identified a cohort of e-cigarette users and never-smokers in the region of central Los Angeles. Using information extracted from the EHR, we assessed temporal trends in the demographic characteristics of e-cigarette users, including race/ethnicity and location of residence. We also used data on urgent medical visits (i.e. emergency department encounters and hospital admissions) occurring during the study period (January 2014 to January 2020) and employed a negative binomial regression model to compare healthcare utilization rates between e-cigarette users and never-smokers.RESULTSWe identified a total of 698 e-cigarette users, in addition to 999 never-smokers, with demographic, clinical, and outcomes data available over the duration of the study period. From the beginning to the end of the study period, e-cigarette use increased across all race/ethnicity groups and across all geographic regions of residence. Notably, e-cigarette users experienced a 4.96 higher rate of urgent medical visits when compared to never-smokers evaluated over the same study period.CONCLUSIONE-cigarettes use continues to expand, with evidence of racial/ethnic as well as geographic variation in uptake. Use of e-cigarette devices is associated with substantially higher rates of urgent healthcare utilization. These findings highlight the need for a more granular understanding of e-cigarette use and enhanced attention to the diversity as well as breadth of the population affected by this burgeoning health crisis.
Normative reference values of the handgrip strength for the Portuguese workers
Authors: Bernardes Sarah Fernandes , Assunção Ana , Fujão Carlos , Carnide Filomena 
Published: January 2020

ABSTRACTAimThis study aims to identify the normative values of handgrip strength for Portuguese workers in the automotive industry.MethodsAbout 1225 employees were invited to participate in the study. The final sample consisted of 656 employees in the assembly area. The handgrip strength was measured in kilograms (kg) using the Jamar digital dynamometer. Two measurements were performed in both hands, totaling four measurements. For the present study, the maximum value was recorded regardless of the hand.Resultsshowed the peak mean values of handgrip strength in the group of women was 34 kg in the age group of 35-39 years, and the group of men the peak mean was 52 kg in the age group of 25-34 years. The most pronounced decline in the female group appears in the age of 30-34 years with 30 kg and the men group the decline occurs of 2kg below the peak force, in the age group between the 40-57 years. This study used a cut-off at 2 SD below by the sex-specific peak mean.ConclusionNormative values can help delineate the career path of workers because they portray risk values according to age, height, and gender. And they can also help in adjusting the morphological and strength characteristics of the worker with the task to be performed, as an example of work above head level.Key MessagesThe handgrip strength is a general indicator of muscle strength, in addition to being closely related to cardiovascular and nutritional diseases. Also, this measure is one of the keys to defining sarcopenia.One of the main findings of the study was found in the group of women aged 30-34 years, with a significant decline in handgrip strength compared to other age groups. Furthermore, the present study, established for the first time, normative values for the handgrip strength of Portuguese workers in the automotive industry.The handgrip strength decline is a crucial predictor of frailty syndrome, and sarcopenia can be checked by the occupational medicine department, individually, by the risk threshold outcomes presents in this study. Also, it is possible to design the conditions work processes associated with the predictive values of HG2 and HG5 and the implementation of the workers’ clinical surveillance system through periodic tests of handgrip strength.
Coordination and assembly of protein complexes encoded across mitochondrial and nuclear genomes is assisted by CLPP2 inArabidopsis thaliana
Authors: Petereit Jakob , Duncan Owen , Murcha Monika W , Fenske Ricarda , Cincu Emilia , Cahn Jonathan , Pružinská Adriana , Ivanova Aneta , Kollipara Laxmikanth , Wortelkamp Stefanie , Sickmann Albert , Lee Jiwon , Lister Ryan , Millar A Harvey , Huang Shaobai 
Published: January 2020

AbstractProtein homeostasis in eukaryotic organelles and their progenitor prokaryotes is regulated by a series of proteases including the caseinolytic protease (CLPP). CLPP has essential roles in chloroplast biogenesis and maintenance, but the significance of the plant mitochondrial CLPP remains unknown and factors that aid coordination of nuclear and mitochondrial encoded subunits for complex assembly in mitochondria await discovery. We generated knock-out lines of the single gene for the mitochondrial CLP protease subunit,CLPP2,inArabidopsis thaliana. Mutants had higher abundance of transcripts from mitochondrial genes encoding OXPHOS protein complexes, while transcripts for nuclear genes encoding other subunits of the same complexes showed no change in abundance. In contrast, the protein abundance of specific nuclear-encoded subunits in OXPHOS complexes I and V increased in CLPP2 knockouts, without accumulation of mitochondrial-encoded counterparts in the same complex. Protein complexes mainly or entirely encoded in the nucleus were unaffected. Analysis of protein import, assembly and function of Complex I revealed that while function was retained, protein homeostasis was disrupted through decreased assembly, leading to accumulation of soluble subcomplexes of nuclear-encoded subunits. Therefore, CLPP2 contributes to the mitochondrial protein degradation network through supporting coordination and assembly of protein complexes encoded across mitochondrial and nuclear genomes.One sentence summaryCLPP contributes to the mitochondrial protein degradation network through supporting coordination and assembly of protein complexes encoded across mitochondrial and nuclear genomes.
The lonely fish is not a loner fish: whole-brain mapping reveals abnormal activity in socially isolated zebrafish
Authors: Tunbak Hande , Vazquez-Prada Mireya , Ryan Thomas , Kampff Adam R. , Dreosti Elena 
Published: January 2020

AbstractThe zebrafish is used to assess the impact of social isolation on behaviour and brain function. As in humans and other social species, early social deprivation reduces social preference in juvenile zebrafish. Whole-brain functional maps of anti-social isolated fish were distinct from anti-social fish found in the normal population. These isolation-induced activity changes revealed profound disruption of neural activity in brain areas linked to social behaviour, such as the preoptic area and hypothalamus. Several of these affected regions are modulated by serotonin, and we found that social preference in isolated fish could be rescued by acutely reducing serotonin levels.
Wnt signaling determines body axis polarity in regeneratingHydratissue
Authors: Wang Rui , Steele Robert E. , Collins Eva-Maria S. 
Published: January 2020

AbstractHow an animal establishes its body axis is a fundamental question in developmental biology. The freshwater cnidarianHydrais an attractive model for studying axis formation because it is radially symmetric, with a single oral-aboral axis. It was recently proposed that the orientation of the new body axis in a regeneratingHydrais determined by the oral-aboral orientation of the actin-myosin contractile processes (myonemes) in the parent animal’s outer epithelial layer. However, because the myonemes are not known to possess polarity, it remained unclear how the oral-aboral polarity of the axis would be defined. As Wnt signaling is known to maintain axis polarity inHydraand bilaterians, we hypothesized that it plays a role in axis specification in excisedHydratissue pieces. We tested this hypothesis using pharmacological perturbations and novel grafting experiments to set Wnt-derived signals and myoneme orientation perpendicular to each other to determine which controls axis formation. Our results demonstrate that Wnt signaling is the dominant encoder of axis information, in line with its highly conserved role in anterior-posterior patterning.
The entorhinal cortical alvear pathway differentially excites interneuron subtypes in hippocampal CA1
Authors: Bell Karen A. , Delong Rayne , Goswamee Priyodarshan , McQuiston A. Rory 
Published: January 2020

AbstractThe entorhinal cortex alvear pathway is a major excitatory input to hippocampal CA1, yet nothing is known about its physiological impact. We investigated the alvear pathway projection and innervation of neurons in CA1 using optogenetics and whole cell patch clamp methods in transgenic mouse brain slices. Using this approach, we show that the medial entorhinal cortical alvear inputs onto both CA1 pyramidal cells and stratum oriens interneurons were monosynaptic, had low release probability, and were mediated by AMPA receptors. Optogenetic theta burst stimulation was unable to elicit suprathreshold activation of CA1 pyramidal neurons but was capable of activating CA1 stratum oriens interneurons. CA1 stratum oriens interneuron subtypes were not equally affected. Higher burst action potential frequencies were observed in parvalbumin-expressing interneurons relative to vasoactive-intestinal peptide-expressing or a subset of oriens lacunosum-moleculare interneurons. Furthermore, alvear excitatory synaptic responses were observed in greater than 70% of PV and VIP interneurons and less than 20% of O-LM cells. Finally, greater than 50% of theta burst-driven inhibitory postsynaptic current amplitudes in CA1 PCs were inhibited by optogenetic suppression of PV interneurons. Therefore, our data suggest that the alvear pathway primarily affects hippocampal CA1 function through feedforward inhibition of select interneuron subtypes.
Conservation genomics of an Australian orchid complex with implications for the taxonomic and conservation status ofCorybas dowlingii
Authors: Wagner Natascha D. , Clements Mark A. , Simpson Lalita , Nargar Katharina 
Published: January 2020

AbstractThis study assessed genomic diversity in an Australian species complex in the helmet orchids to clarify taxonomic delimitation and conservation status of the threatened speciesCorybas dowlingii,a narrow endemic from southeast Australia. Taxonomic delimitation between the three closely related speciesC. aconitiflorus,C. barbarae,andC. dowlingiihas been mainly based on floral traits which exhibit varying degrees of overlap, rendering species delimitation in the complex difficult. Genomic data for the species complex was generated using double-digest restriction-site associated DNA (ddRAD) sequencing. Maximum likelihood, NeighborNet, and Bayesian structure analyses showed genetic differentiation within the species complex and retrieved genomic signatures consistent with hybridisation and introgression betweenC. aconitiflorusandC. barbarae,and an intermediate genetic position ofC. dowlingiiindicating a hybrid origin of the species. The genetic structure analysis showed varying levels of genetic admixture for severalC. aconitiflorus,C. barbarae,andC. dowlingiisamples, thus further corroborating the presence of hybridisation and introgression within the species complex. The taxonomic status ofC. dowlingiiD.L.Jones was revised toC. × dowlingiiD.L.Jonesstat. nov.to reflect its hybrid origin. The conservation status ofC. × dowlingiiwas assessed based on key ecological and ethical aspects, and recommendations made regarding its conservation status in Australian conservation legislation.
Continuous detection of glucose and insulin in live animals
Authors: Poudineh Mahla , Maikawa Caitlin L. , Ma Eric Yue , Pan Jing , Mamerow Dan , Hang Yan , Baker Sam W. , Beirami Ahmad , Eisenstein Michael , Kim Seung , Vučković Jelena , Appel Eric A. , Soh H. Tom 
Published: January 2020

AbstractReal-time biosensors that can continuously measure circulating biomoleculesin vivowould provide valuable insights into a patients’ health status and their response to therapeutics even when there is considerable variability in pharmacokinetics and pharmacodynamics across patient populations. Unfortunately, current real-time biosensors are limited to a handful of analytes (e.g.glucose and blood oxygen) and are limited in sensitivity (high nanomolar). In this work, we describe a general approach for continuously and simultaneously measuring multiple analytes with picomolar sensitivity and sub-second temporal resolution. As exemplars, we report the simultaneous detection of glucose and insulin at picomolar concentrations in live diabetic rats. Using our system, we demonstrate the capacity to resolve inter-individual differences in the pharmacokinetic responses to insulin and discriminate profiles from different insulin formulations at a high temporal resolution. Critically, our approach is general and could be readily modified to continuously and simultaneously measure other circulating analytesin vivoby swapping the affinity reagents, thus making it a versatile tool for biomedical research.
The ubiquitin ligase Ariadne-1 regulates NSF for neurotransmitter release
Authors: Ramírez Juanma , Morales Miguel , Osinalde Nerea , Martínez-Padrón Imanol , Mayor Ugo , Ferrús Alberto 
Published: January 2020

ABSTRACTAriadne-1 (Ari-1) is an essential E3 ubiquitin-ligase whose neuronal substrates are yet to be identified. We have used anin vivoubiquitin biotinylation strategy coupled to quantitative proteomics to identify putative Ari-1 substrates inDrosophilaheads. Sixteen candidates met the established criteria. Amongst those, we identified Comatose (Comt), the homologue of the N-ethylmaleimide sensitive factor (NSF). Using anin vivoGFP pulldown approach, we validate Comt/NSF to be an ubiquitination substrate of Ari-1 in fly neurons. The interaction results in the monoubiquitination of Comt/NSF. We also report that Ari-1 loss of function mutants display a lower rate of spontaneous neurotransmitter release due to failures at the pre-synaptic side. By contrast, evoked release in Ari-1 mutants is enhanced in a Ca2+dependent manner without modifications in the number of active zones, indicating that the probability of release per synapse is increased in these mutants. The distinct Ari-1 mutant phenotypes in spontaneous versus evoked release indicate that NSF activity discriminates the two corresponding protein ensembles that mediate each mode of release. Our results, thus, provide a mechanism to regulate NSF activity in the synapse through Ari-1-dependent ubiquitination.
CCSN: Single Cell RNA Sequencing Data Analysis by Conditional Cell-specific Network
Authors: Li Lin , Dai Hao , Fang Zhaoyuan , Chen Luonan 
Published: January 2020

AbstractThe rapid advancement of single cell technologies has shed new light on the complex mechanisms of cellular heterogeneity. However, compared with bulk RNA sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq) suffers from higher noise and lower coverage, which brings new computational difficulties. Based on statistical independence, cell-specific network (CSN) is able to quantify the overall associations between genes for each cell, yet suffering from a problem of overestimation related to indirect effects. To overcome this problem, we propose the “conditional cell-specific network” (CCSN) method, which can measure the direct associations between genes by eliminating the indirect associations. CCSN can be used for cell clustering and dimension reduction on a network basis of single cells. Intuitively, each CCSN can be viewed as the transformation from less “reliable” gene expression to more “reliable” gene-gene associations in a cell. Based on CCSN, we further design network flow entropy (NFE) to estimate the differentiation potency of a single cell. A number of scRNA-seq datasets were used to demonstrate the advantages of our approach: (1) one direct association network for one cell; (2) most existing scRNA-seq methods designed for gene expression matrices are also applicable to CCSN-transformed degree matrices; (3) CCSN-based NFE helps resolving the direction of differentiation trajectories by quantifying the potency of each cell. CCSN is publicly available athttp://sysbio.sibcb.ac.cn/cb/chenlab/soft/CCSN.zip.