bluuebunny/crossref_metadata_2025_split huggingface dataset:
The meaning of donor-specific antibodies after heart transplant
Authors: Barten Markus J. , Zuckermann Andreas 
Published: April 2019

Purpose of review
Antibody-mediated rejection (AMR) is a major contributor of impaired long-term survival after heart transplantation (HTx). The presence of circulating donor-specific antihuman leukocyte antigen (HLA) antibodies (DSAs) is considered as a mandatory criterion for AMR after HTx. DSA are known prognostic biomarkers of outcome, for example, recipients with de-novo DSA have a three-fold increased risk of mortality.

Recent findings
Although the awareness of the impact and prognosis of DSA on the survival has been increased in the HTx community over the last decade, the management of DSA pre and posttransplant varies among centers and is mainly based on the experience of transplant physicians. Thus, firm consensus strategies for each HTx recipient should be established by a center advisory board of experts in the field of HLA genetics, transplantation immunology, and HTx to evaluate the immunological risk preoperatively and also continuously during the posttransplant course. Consequently, the recent advances of invasive and noninvasive diagnostic tools should be applied, according to the risk, laboratory findings, and clinical events of the recipient. Such individual strategy will result in tailored therapeutic options.

Summary
Novel standards for the management of DSA in HTx recipients on the basis of an interdisciplinary approach of experts will improve diagnostics for personalized medicine.
Men Who Have Sex With Men With Mycoplasma genitalium–Positive Nongonococcal Urethritis Are More Likely to Have Macrolide-Resistant Strains Than Men With Only Female Partners: A Prospective Study
Authors: McIver Ruthy , Jalocon Dean , McNulty Anna , Jeoffreys Neisha J. , Chen Sharon Chih-Ann , Power Melissa , Couldwell Deborah Leone 
Published: April 2019

Background

Mycoplasma genitalium was previously less common among men who have sex with men (MSM) compared with men with only female partners (MSW) in men with nongonococcal urethritis (NGU) in Sydney, Australia. We aimed to determine the prevalence of M. genitalium and of macrolide-resistant M. genitalium in men with NGU and to compare differences between prevalence and resistance rates between MSM and MSW.

Methods
We enrolled 588 men with NGU in a prospective study at two urban sexual health services. The ResistancePlus MG assay (SpeeDx, Australia) was used to detect both M. genitalium, and macrolide resistance-associated mutations in first-void urine samples. Demographic, behavioral and clinical data were analyzed to investigate associations with M. genitalium infection or the presence of macrolide resistance.

Results

Mycoplasma genitalium prevalence was 12.8% (75 of 588) overall and among MSM (12.8% [39 of 306]) and MSW (12.8% [36 of 282]; risk ratio [RR], 1.00; 95% confidence interval [CI], 0.65–1.52). Overall, 70.7% (53 of 75) of M. genitalium strains were macrolide-resistant, with significantly more resistance among MSM (89.7%, 35 of 39) than MSW (50%, 18 of 36) (RR, 1.80; 95% CI, 1.27–2.54; P = 0.001). On multivariate analysis, the presence of M. genitalium macrolide resistance mutations was independently associated with having male sexual partners compared with having only female partners (RR, 1.55; 95% CI, 1.02–2.38; P = 0.042).

Conclusions
Prevalence of M. genitalium among men with NGU is now similar for MSW and MSM and has increased locally from 5.2% to 12.8% within the last 10 years. Men who have sex with men are significantly more likely than MSW to harbor macrolide-resistant M. genitalium infections. This has treatment implications.
Local and Visiting Physician Perspectives on Short Term Surgical Missions in Guatemala
Authors: Coughran Alanna J. , Merrell Sylvia Bereknyei , Pineda Carlos , Sceats Lindsay A. , Yang George P. , Morris Arden M. 
Published: April 2019

Objective:
To explore the impact of short-term surgical missions (STMs) on medical practice in Guatemala as perceived by Guatemalan and foreign physicians.

Summary Background Data:
STMs send physicians from high-income countries to low and middle-income countries to address unmet surgical needs. Although participation among foreign surgeons has grown, little is known of the impact on the practice of foreign or local physicians.

Methods:
Using snowball sampling, we interviewed 22 local Guatemalan and 13 visiting foreign physicians regarding their perceptions of the impact of Guatemalan STMs. Interviews were transcribed verbatim, iteratively coded, and analyzed to identify emergent themes. Findings were validated through triangulation and searching for disconfirming evidence.

Results:
We identified 2 overarching domains. First, the delivery of surgical care by both Guatemalan and foreign physicians was affected by practice in the STM setting. Differences from usual practice manifested as occasionally inappropriate utilization of skills, management of postoperative complications, the practice of perioperative care versus “pure surgery,” and the effect on patient–physician communication and trust. Second, both groups noted professional and financial implications of participation in the STM.

Conclusions:
While Guatemalan physicians reported a net benefit of STMs on their careers, they perceived STMs as an imperfect solution to unmet surgical needs. They described missed opportunities for developing local capacity, for example through education and optimal resource planning. Foreign physicians described costs that were manageable and high personal satisfaction with STM work. STMs could enhance their impact by strengthening working relationships with local physicians and prioritizing sustainable educational efforts.
Decision Aid Video for Treatment Selection in Latinas With Symptomatic Pelvic Organ Prolapse: A Randomized Pilot Study
Authors: Montoya T. Ignacio , Rondeau Nancy U. , Maldonado P. Antonio , Mallett Veronica T. 
Published: April 2019

Objectives
To assess impact of a decision aid video in Latina patients with symptomatic pelvic organ prolapse (POP) on knowledge, satisfaction and decisional conflict related to initial treatment selection.

Methods
Pilot study with randomized prospective design. Thirty Latina women with symptomatic POP were randomized to a decision aid intervention plus standard care (N = 15) or standard care alone (N = 15) group. Decision aid intervention consisted of a 10-minute video presented at time of initial evaluation for POP. Outcome measures included the Prolapse and Incontinence Knowledge Quiz (“Knowledge”), the Satisfaction with Decision (“Satisfaction”) and Decisional Conflict (DCS) scales, and were assessed at 4 different timepoints: after initial visit, and at 1, 3 and 6 months after. Data was analyzed using repeated-measures ANOVA and pairwise between-group comparisons.

Results
Demographic and baseline data were similar between groups. There was a significant interaction between groups and time on the Knowledge scores (P = 0.03). Knowledge scores were higher at the initial visit in the intervention group (10.6 ± 0.8 vs 9.53 ± 1.4, P = 0.014). Satisfaction scores were lower in the intervention group on longitudinal analysis, indicating higher satisfaction (P = 0.02). There was no difference on overall Decisional Conflict scores between groups. The intervention group had lower scores on the “effective decision” DCS subscale at 3 and 6 months and “informed” DCS subscale at 3 months.

Conclusions
A decision aid video intervention in Latina women with POP used at the time of initial evaluation may help the patient make a more informed treatment decision by increasing condition-related knowledge and lead to greater long-term satisfaction.
Altered monocyte and NK cell phenotypes correlate with posttrauma infection
Authors: Seshadri Anupamaa , Brat Gabriel A. , Yorkgitis Brian K. , Giangola Matt , Keegan Joshua , Nguyen Jennifer P. , Li Wei , Nakahori Yasutaka , Wada Takeshi , Hauser Carl , Salim Ali , Askari Reza , Lederer James A. 
Published: April 2019

BACKGROUND
Trauma induces a complex immune response, requiring a systems biology approach to capture multicellular changes. Using mass cytometry by time-of-flight (CyTOF), we evaluated time-dependent changes in peripheral blood in trauma patients to identify changes correlated with infection.

METHODS
Total leukocytes were prepared via red blood cell lysis using peripheral blood samples from trauma patients with an Injury Severity Score greater than 20 at Days 1, 3, and 5 after injury, and from age- and sex-matched uninjured controls. Cells were stained using a 33-marker immunophenotyping CyTOF panel. Statistics were calculated using one-way analysis of variance with multiple comparisons.

RESULTS
The CyTOF staining demonstrated changes in many cell subsets. The mean expression intensity of CD86 on monocytes decreased significantly at all time points after injury. When the patients were stratified based on development of infection, there was a trend to decreased CD86 expression on monocytes of those patients that developed subsequent infection. Based on stratification, we identified significantly increased expression of CD39 on NK cells only in patients that developed an infection.

CONCLUSION
This study used a systems biology approach to identify novel changes in circulating immune cell subsets in trauma patients correlating with post-traumatic infection. Decreased expression of CD86, a costimulatory molecule, on monocytes demonstrates that trauma affects the innate system's ability to control T-cell immunity. We also found that CD39 expression on NK cells increased significantly in patients with subsequent infection. CD39 is a protein that generates adenosine, which has immunosuppressive effects on several immune cell types including NK cells. In summary, our results point to pathways that may be central to second-hit infections and further study to delineate these pathways could be key to generating clinical biomarkers or targeted immune therapies for trauma patients.

LEVEL OF EVIDENCE
Prognostic study, level II.
Congenital Cranial Dysinnervation Disorder: An Unusual Phenotype With Multiple Cranial Neuropathies and Novel Neuroimaging Findings
Authors: Salman Michael S. , Mulholland Conor , Wrogemann Jens , Marin Samantha E. 
Published: April 2019

Abstract:
Congenital cranial dysinnervation disorders result from a maldevelopment of brainstem nuclei and/or cranial nerves. In some cases, specific genetic abnormalities have been identified. We expand the clinical phenotype of these disorders with the report of a 28-month-old girl who was initially evaluated for seizures and was found to have right sixth nerve palsy, small optic discs with reduced vision in her right eye. Her development was delayed. Brain MRI showed multiple abnormalities involving other cranial nerves, the optic chiasm and brainstem. Her developmental delay and seizure disorder suggest additional cortical involvement.
Functional Genomic Complexity Defines Intratumor Heterogeneity and Tumor Aggressiveness in Liver Cancer
Authors: Kwon So Mee , Budhu Anuradha , Woo Hyun Goo , Chaisaingmongkol Jittiporn , Dang Hien , Forgues Marshonna , Harris Curtis C. , Zhang Gao , Auslander Noam , Ruppin Eytan , Mahidol Chulabhorn , Ruchirawat Mathuros , Wang Xin Wei 
Published: April 2019

ABSTRACTBackgroundChronic inflammation and chromosome aneuploidy are major traits of primary liver cancer (PLC), which represent the second most common cause of cancer related death worldwide. Increased cancer fitness and aggressiveness of PLC may be achieved by enhancing tumoral genomic complexity that alters tumor biology.MethodHere, we developed a scoring method, namely functional genomic complexity (FGC), to determine the degree of molecular heterogeneity among 580 liver tumors with diverse ethnicities and etiologies by assessing integrated genomic and transcriptomic data.ResultsWe found that tumors with higher FGC scores are associated with chromosome instability and TP53 mutations, and a worse prognosis, while tumors with lower FGC scores have elevated infiltrating lymphocytes and a better prognosis. These results indicate that FGC scores may serve as a surrogate to define genomic heterogeneity of PLC linked to chromosomal instability and evasion of immune surveillance.ConclusionOur findings demonstrate an ability to define genomic heterogeneity and corresponding tumor biology of liver cancer based only on bulk genomic and transcriptomic data. Our data also provide a rationale for applying this approach to survey liver tumor immunity and to stratify patients for immune-based therapy.STATEMENT OF SIGNIFICANCEGenomic heterogeneity contributes to therapeutic failure and poor outcome in patients with liver cancer and poses a challenge in defining targeted therapy. Our findings demonstrate an ability to define genomic heterogeneity and corresponding tumor biology of liver cancer based only on bulk genomic and transcriptomic data. Our data also provide a rationale for applying this approach to survey liver tumor immunity and to stratify patients for immune-based therapy. \body
Single cell RNA sequencing reveals cellular diversity of trisomy 21 retina
Authors: Wu Jihong , Ding Xiangning , Hu Fangyuan , Xu Zaoxu , Zhang Shenghai , Liang Langchao , Chai Chaochao , Zhong Jixing , Wang Shiyou , Lin Xiumei , Chen Yin , Feng Qikai , Zhu Jiacheng , Jiang Sanjie , Xia Jun , Li Wei , Gao Ya , Li Jiankang , Zhang Jingxuan , He Zhikai , Xue Shen , Guo Guanglin , Xu Ping , Gao Fengjuan , Wang Dandan , Zhang Daowei , Chen Dongsheng , Sun Xinghuai , Chen Fang 
Published: April 2019

AbstractRetina is a crucial tissue for the capturing and processing of light stimulus. Characterization of the retina at single cell level is essential for the understanding of its biological functions. A variety of abnormalities in terms of morphology and function were reported in T21 retina. To evaluate the effects of chromosome aneuploidy on retina development, we characterized single cell transcriptional profiles of a T21 fetus and performed comprehensive bioinformatic analyses. Our data revealed the diversity and heterogeneity of cellular compositions in T21 retina. In total, we identified seven major cell types, and detected several subtypes within each cell type, followed by the detection of corresponding molecular markers including previously reported ones and a series of novel markers. Our analyses identified extensive communication networks between distinct cellular types, among which a few ligand-receptor interactions were associated with the development of retina and immunoregulatory interactions. Taken together, our data provided the first single cell transcriptome profile for human T21 retina which facilitates our understanding on the dosage effects of chromosome 21 on the development of retina.
Slow andad hoc: Unravelling the two features characterizing the development of bacterial resistance to membrane active peptides
Authors: Majumder Ayan , Prakash Meher K. 
Published: April 2019

AbstractMembrane disrupting drugs such as antimicrobial peptides are being considered as a solution to counter the problem of antibiotic resistance. Although it can be intuitively imagined that bacteria will eventually develop resistance to this class of drugs as well, the concern has largely been ignored. Drawing upon the experimental data from the resistance ofStaphylococcus aureusto antimicrobial peptides, we theoretically model the membrane adaptation under drug pressure. Using our model, we simulate the serial passage experiments with and without the drug pressure, and use the comparisons with experiments to estimate the unknown kinetic parameters. While the development of resistance to enzyme or membrane targeting drugs are both driven by spontaneous mutations, an additional lysylation step required in the latter slows the development of resistance. By quantifying the tradeoff between the gain in fitness under drug pressure and a loss in growth due to membrane modification, our model shows a fast reversal of membrane composition in drug free conditions, re-sensitizing the bacterium to the drugs.
Integrated analysis of the miRNA-mRNA network associated with LMP1 gene in nasopharyngeal carcinoma
Authors: Yang Yang , Liu Wen , Zhang Yan , Wu Shuo , Luo Bing 
Published: April 2019

AbstractEpstein-Barr virus oncogenic latent membrane protein 1 (LMP1) has been known to play important roles in nasopharyngeal carcinoma (NPC). LMP1 gene also induced a variety of microRNAs (miRNAs) which bear pivotal roles in regulation of mRNAs expression. However, little was known about the global change of mRNAs and miRNAs induced by LMP1 gene in NPC. In our study, one NPC tissue microarray profile and two LMP1-associated microarray expression profiles data were downloaded from the Gene Expression Omnibus database. A protein-protein interaction network was constructed by using bioinformatics platform Gene-Cloud of Biotechnology Information (GCBI). 78 differentially expressed miRNAs and 3322 differentially expressed genes were identified in order to generate a macroscopic network between miRNAs and mRNAs associated with LMP1 gene. In addition, two significant models were generated to illustrate the expression tendency. Our study provided a way to reveal the interaction between miRNAs and mRNAs in LMP1 axis, bringing insights into the pathogenesis of NPC.
CNNcon: A Quantitative Imaging Tool for Lung CT Image Feature Analysis
Authors: Causey Jason , Qualls Jake , Moore Jason H. , Prior Fred , Huang Xiuzhen 
Published: April 2019

AbstractBackgroundLung CT scans are widely used for lung cancer screening and diagnosis. Current research focuses on quantitative analytics (radiomics) to improve screening and detection accuracy. However there are very limited numbers of portable software tools for automatic lung CT image analysis.ResultsHere we build a Docker container, CNNcon, as a quantitative imaging tool for analyzing lung CT image features. CNNcon is developed from our recently published algorithm for nodule analysis, based on convolutional neural networks (CNN). When provided with a list of the centroid coordinates of regions of interest (ROI) in a volumetric CT study containing potential lung nodules, CNNcon can automatically generate highly accurate malignancy prediction of each ROI. CNNcon can also generate a vector of image features of each ROI, to facilitate further analyses by combining image features and other clinical features. As a Docker container, CNNcon is portable to various computer systems, convenient to install, and easy to use. CNNcon was tested on different computer systems and generated identical results.ConclusionsWe anticipate that CNNcon will be a useful tool and broadly acceptable to the research community interested in quantitative image analysis.AvailabilityCNNcon and document are publicly available and can be downloaded from the website: http://bioinformatics.astate.edu/CNN-Container/
Germline genomic patterns are associated with cancer risk, oncogenic pathways and clinical outcomes
Authors: Feng Xiaowen , Xu Xue , Li Derek , Cui Qinghua , Wang Edwin 
Published: April 2019

SummaryGermline genetic polymorphism is prevalent and inheritable. So far mutations of a handful of genes have been associated with cancer risks. For example, women who harbor BRCA1/2 germline mutations have a 70% of cumulative breast cancer risk; individuals with congenital germline APC mutations have nearly 100% of cumulative colon cancer by the age of fifty. At present, gene-centered cancer predisposition knowledge explains only a small fraction of the inheritable cancer cases. Here we conducted a systematic analysis of the germline genomes of cancer patients (n=9,712) representing 22 common cancer types along with non-cancer individuals (n=16,670), and showed that seven germline genomic patterns, or significantly repeatedly occurring sequential mutation profiles, could be associated with both carcinogenesis processes and cancer clinical outcomes. One of the genomic patterns was significantly enriched in the germline genomes of patients who smoked than in those of non-smoker patients of 13 common cancer types, suggesting that the germline genomic pattern was likely to confer an elevated carcinogenesis sensitivity to tobacco smoke. Several patterns were also associated with somatic mutations of key oncogenic genes and somatic-mutational signatures which are associated with higher genome instability in tumors. Furthermore, subgroups defined by the germline genomic patterns were significantly associated with distinct oncogenic pathways, tumor histological subtypes and prognosis in 12 common cancer types, suggesting that germline genomic patterns enable to inform treatment and clinical outcomes. These results demonstrated that genetic cancer risk and clinical outcomes could be encoded in germline genomes in the form of not only mutated genes, but also specific germline genomic patterns, which provided a novel perspective for further investigation.
Personality maturation among emerging adults and future career success
Authors: Kalfon Hakhmigari Maor , Michaeli Yossi , J. Dickson Daniel , Scharf Miri , Shulman Shmuel 
Published: April 2019

Purpose
The purpose of this paper is to examine the role of maturation processes – personality change and reflectivity as characterized by greater awareness to self and others – during emerging adulthood in predicting career success.

Design/methodology/approach
A sample of 205 of Israeli emerging adults was followed over a 12-year period. Participants completed measures of self-criticism at age 23 and 29, reflectivity at the age of 29 and subjective and objective career outcomes such as satisfaction with work and level of income at the age of 35. Hierarchical regressions determined the extent that decreases in self-criticism as well as greater reflectivity that predicted future career success.

Findings
The findings of this paper indicated that greater decreases in self-criticism were longitudinally associated with less frequent negative experiences at work and lesser tendency to have doubts about one’s career. Greater reflective capacity was longitudinally associated with a future higher income, greater career satisfaction and a stronger perception of one’s career as a means to implement inner interests.

Research limitations/implications
The results of this paper suggest that decreasing negative self-perception and enhancing awareness about self and others might facilitate a future career success.

Originality/value
This is among the first studies that demonstrate the role of personality maturation during emerging adulthood for future career success.
Organizational citizenship behaviors in the era of changing employment patterns
Authors: Lo Presti Alessandro , Manuti Amelia , Briscoe Jon P. 
Published: April 2019

PurposeThe increasing flexibility and discontinuity of labor relations have been associated with the development of new forms of psychological contracts as well as the development of more self-directed and mobile career attitudes. The purpose of this paper is to examine the relationship between the forms of psychological contract and protean/boundaryless career attitudes on the one hand and organizational citizenship behaviors (OCB) on the other.Design/methodology/approachIn total, 458 employees of three large Italian organizations were sampled through a self-report questionnaire. Zero-order correlations were carried out to examine the associations between study variables while dominance analysis, along with multiple linear regression, was used for evaluating their unique contribution with respect to OCB.FindingsOCB were positively predicted by relational and balanced psychological contracts, protean career attitude and boundaryless mindset.Practical implicationsOrganizations must pay particular attention to the content of the psychological contract and the career attitudes of their employees because they influence their willingness to carry out OCB.Originality/valueThe results add new evidence to the careers literature in terms of boundary conditions with regard to the effects of protean and boundaryless career attitudes as well as different forms of psychological contracts.