bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparison of Two Techniques for Generating Nowcasting Ensembles. Part II: Analogs Selection and Comparison of Techniques
Authors: Atencia Aitor , Zawadzki Isztar 
Published: March 2015

Abstract
Nowcasting is the short-range forecast obtained from the latest observed state. Currently, heuristic techniques, such as Lagrangian extrapolation, are the most commonly used for rainfall forecasting. However, the Lagrangian extrapolation technique does not account for changes in the motion field or growth and decay of precipitation. These errors are difficult to analytically model and are normally introduced by stochastic processes. According to the chaos theory, similar states, also called analogs, evolve in a similar way plus an error related with the predictability of the situation. Consequently, finding these states in a historical dataset provides a way of forecasting that includes all the physical processes such as growth and decay, among others.
The difficulty of this approach lies in finding these analogs. In this study, recent radar observations are compared with a 15-yr radar dataset. Similar states within the dataset are selected according to their spatial rainfall patterns, temporal storm evolution, and synoptic patterns to generate ensembles. This ensemble of analog states is verified against observations for four different events. In addition, it is compared with the previously mentioned Lagrangian stochastic ensemble by means of different scores. This comparison shows the weaknesses and strengths of each technique. This could provide critical information for a future hybrid analog–stochastic nowcasting technique.
Gender Analysis in the Outcomes of a Lifestyle Intervention Among Patients Who Had an Open Heart Surgery
Authors: Kadda Olga , Manginas Athanasios , Stavridis George , Balanos Dimitris , Kotiou Maria , Panagiotakos Demosthenes B. 
Published: March 2015

The aim of this study was to evaluate the gender-oriented differences in the outcomes of a lifestyle intervention trial (diet, smoking cessation, and exercise) among patients who had open heart surgery. A randomized, nonblind intervention study was performed on 500 patients who had open heart surgery. Immediately after hospital discharge, 250 patients were randomly allocated lifestyle intervention by receiving oral and written information in the form of a booklet with specific educational information for postoperative rehabilitation. The remaining 250 patients received the regular oral instructions. The applied lifestyle intervention proved to be beneficial only in men as far as quitting smoking (relative risk [RR]: 0.36, confidence interval [CI]: 0.16-0.80; P = .01) and returning to work (RR: 0.35, CI: 0.13-0.92; P = .03) are concerned. For both genders, no significant associations between dietary and physical activity recommendations were observed. Conclusion: Lifestyle nursing intervention immediately after open heart surgery had a beneficial effect on men 1 year after the surgery but not on women. Thus, there is a need for gender-specific studies among women.
Fresh Osteochondral Allografts in the Knee
Authors: Gracitelli Guilherme C. , Meric Gokhan , Briggs Dustin T. , Pulido Pamela A. , McCauley Julie C. , Belloti João Carlos , Bugbee William D. 
Published: March 2015

Background: In most treatment algorithms, osteochondral allograft (OCA) transplantation is regarded as an alternative salvage procedure when other, previous reparative treatments have failed. Purpose: To compare the outcomes of a retrospective matched-pair cohort of (1) primary OCA transplantation and (2) OCA transplantation after failure of previous subchondral marrow stimulation. Study Design: Cohort study; Level of evidence, 3. Methods: An OCA database was used to identify 46 knees that had OCA transplantation performed as a primary treatment (group 1) and 46 knees that underwent OCA transplantation after failure of previous subchondral marrow stimulation (group 2). All patients had a minimum of 2 years’ follow-up. Patients in each group were matched for age (±5 years), diagnosis (osteochondral lesion, degenerative chondral lesion, traumatic chondral injury), and graft size (small, <5 cm2; medium, 5-10 cm2; large, >10 cm2). The groups had similar body mass indexes, sex distributions, and graft locations (femoral condyle, patella, and trochlea. The number and type of further surgeries after the OCA transplantation were assessed; failure was defined as any reoperation resulting in removal of the graft. Functional outcomes were evaluated by use of the modified Merle d’Aubigné-Postel (18-point) scale, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Knee injury and Osteoarthritis Outcomes Score (KOOS), and the Knee Society function (KS-F) scale. Patient satisfaction, according to a 5-point scale from “extremely satisfied” to “dissatisfied,” was recorded at the latest follow-up. Results: Eleven of 46 knees (24%) in group 1 had reoperations, compared with 20 of 46 knees (44%) in group 2 ( P = .04). The OCA was classified as a failure in 5 knees (11%) in group 1 and 7 knees (15%) in group 2 ( P = .53). At 10 years of follow-up, survivorship of the graft was 87.4% and 86% in groups 1 and 2, respectively. Both groups showed improvement in pain and function on all subjective scores from preoperatively to the latest follow-up (all P < .001). Results showed that 87% of patients in group 1 and 97% in group 2 were “satisfied” or “extremely satisfied” with the OCA transplantation. Conclusion: Favorable results were shown in both groups with significant improvement of functional scores and excellent survivorship. Despite the higher reoperation rate in the previously treated group, previous subchondral marrow stimulation did not adversely affect the survivorship and functional outcome of OCA transplantation.
The Safety and Feasibility of Admitting Patients With Intracerebral Hemorrhage to the Step-Down Unit
Authors: Hafeez Shaheryar , Behrouz Réza 
Published: March 2015

Background: Intracerebral hemorrhage (ICH) is a devastating and costly condition. Although the American Heart Association/American Stroke Association recommends admitting patients with ICH to a neurocritical care unit (NCCU), this strategy may accrue unnecessary cost for patients with relatively milder presentation. We conducted a prospective observational study to determine the safety and feasibility of admitting patients with mild ICH directly to a step-down unit (SDU) instead of an NCCU. Methods: Consecutive patients with “mild presentation,” defined as a combination of ICH score ≤2, National Institutes of Health Stroke Scale (NIHSS) ≤ 15, and Graeb score ≤2 (if intraventricular hemorrhage was present), were admitted to the SDU. Data were collected on age, gender as well as the initial NIHSS, Glasgow Coma Scale (GCS), ICH, and Graeb scores. Primary end point was any complication or death during hospital stay. Results: Twenty patients were admitted to the SDU. No patient was transferred to the NCCU from the SDU. One patient, who eventually died, had respiratory insufficiency due to hospital-acquired pneumonia. Conclusion: Admission of ICH patients with mild symptoms to the SDU is safe and feasible. Larger prospective studies are needed to define the specific criteria for admission.
Flatfoot in School-Age Children
Authors: Sadeghi-Demneh Ebrahim , Jafarian Fahimehsadat , Melvin Jonathan M. A. , Azadinia Fatemeh , Shamsi Fatemeh , Jafarpishe Mohamad 
Published: March 2015

Background. Flatfoot has been shown to cause abnormal stresses on the foot and lower extremity. The altered mechanical stresses on these structures can aggravate the foot deformity. Screening of the flatfoot and its associated factors helps detect underlying risks influencing the stresses on the foot. The purpose of this study was to analyze the structure of the medial foot arch and investigate its associated factors in students, aged 7 to 14 years. Methods. Multistage cluster sampling was used and each cluster included 2 other random sampling levels. A total of 667 Iranian school children were recruited and their feet were bilaterally evaluated using a static footprint while standing in a fully weightbearing position. The footprint, an observational measurement, and a questionnaire were used for the foot assessment. Results. The prevalence of flatfoot was 17.1% in the population studied. There was no gender difference but the prevalence of flatfoot did decrease with age. The significant differences were observed in the prevalence of flatfoot between normal-weight, overweight, and obese groups (P < .01); more overweight participants had flatter feet. Conclusion. This study demonstrated that development of the longitudinal plantar arch in school-age children is influenced by age and weight. Age and weight were the primary predictive factors of flatfoot. Levels of Evidence: Prognostic, Level IV: Case series
Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study
Authors: Tikk Kaja , Sookthai Disorn , Fortner Renée T , Johnson Theron , Rinaldi Sabina , Romieu Isabelle , Tjønneland Anne , Olsen Anja , Overvad Kim , Clavel-Chapelon Françoise , Baglietto Laura , Boeing Heiner , Trichopoulou Antonia , Lagiou Pagona , Trichopoulos Dimitrios , Masala Giovanna , Krogh Vittorio , Tumino Rosario , Ricceri Fulvio , Mattiello Amalia , Agudo Antonio , Menéndez Virginia , Sánchez María-José , Amiano Pilar , Chirlaque Maria-Dolores , Barricarte Aurelio , Bueno-de-Mesquita HBas , Monninkhof Evelyn M , Onland-Moret N Charlotte , Andresson Anne , Sund Malin , Weiderpass Elisabete , Khaw Kay-Tee , Key Timothy J , Travis Ruth C , Merritt Melissa A , Riboli Elio , Dossus Laure , Kaaks Rudolf 
Published: March 2015

Abstract
Introduction
The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.

Methods
We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects.

Results
We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), Ptrend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet = 0.98) or baseline HT use (Phet = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend = 0.06 vs Ptrend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors <4 years compared to ≥4 years after blood donation (Ptrend = 0.01 vs Ptrend = 0.63; Phet = 0.04) and among nulliparous women compared to parous women (Ptrend = 0.03 vs Ptrend = 0.15; Phet = 0.07).

Conclusions
Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.
Identifying candidate drivers of alcohol dependence-induced excessive drinking by assembly and interrogation of brain-specific regulatory networks
Authors: Repunte-Canonigo Vez , Shin William , Vendruscolo Leandro F , Lefebvre Celine , van der Stap Lena , Kawamura Tomoya , Schlosburg Joel E , Alvarez Mariano , Koob George F , Califano Andrea , Sanna Pietro Paolo 
Published: March 2015

Abstract
Background
A systems biology approach based on the assembly and interrogation of gene regulatory networks, or interactomes, was used to study neuroadaptation processes associated with the transition to alcohol dependence at the molecular level.

Results
Using a rat model of dependent and non-dependent alcohol self-administration, we reverse engineered a global transcriptional regulatory network during protracted abstinence, a period when relapse rates are highest. We then interrogated the network to identify master regulator genes that mechanistically regulate brain region-specific signatures associated with dependent and non-dependent alcohol self-administration. Among these, the gene coding for the glucocorticoid receptor was independently identified as a master regulator in multiple brain regions, including the medial prefrontal cortex, nucleus accumbens, central nucleus of the amygdala, and ventral tegmental area, consistent with the view that brain reward and stress systems are dysregulated during protracted abstinence. Administration of the glucocorticoid antagonist mifepristone in either the nucleus accumbens or ventral tegmental area selectively decreased dependent, excessive, alcohol self-administration in rats but had no effect on non-dependent, moderate, alcohol self-administration.

Conclusions
Our study suggests that assembly and analysis of regulatory networks is an effective strategy for the identification of key regulators of long-term neuroplastic changes within specific brain regions that play a functional role in alcohol dependence. More specifically, our results support a key role for regulatory networks downstream of the glucocorticoid receptor in excessive alcohol drinking during protracted alcohol abstinence.
Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy
Authors: Angelova Mihaela , Charoentong Pornpimol , Hackl Hubert , Fischer Maria L , Snajder Rene , Krogsdam Anne M , Waldner Maximilian J , Bindea Gabriela , Mlecnik Bernhard , Galon Jerome , Trajanoski Zlatko 
Published: March 2015

Abstract
Background
While large-scale cancer genomic projects are comprehensively characterizing the mutational spectrum of various cancers, so far little attention has been devoted to either define the antigenicity of these mutations or to characterize the immune responses they elicit. Here we present a strategy to characterize the immunophenotypes and the antigen-ome of human colorectal cancer.

Results
We apply our strategy to a large colorectal cancer cohort (n = 598) and show that subpopulations of tumor-infiltrating lymphocytes are associated with distinct molecular phenotypes. The characterization of the antigenome shows that a large number of cancer-germline antigens are expressed in all patients. In contrast, neo-antigens are rarely shared between patients, indicating that cancer vaccination requires individualized strategy. Analysis of the genetic basis of the tumors reveals distinct tumor escape mechanisms for the patient subgroups. Hypermutated tumors are depleted of immunosuppressive cells and show upregulation of immunoinhibitory molecules. Non-hypermutated tumors are enriched with immunosuppressive cells, and the expression of immunoinhibitors and MHC molecules is downregulated. Reconstruction of the interaction network of tumor-infiltrating lymphocytes and immunomodulatory molecules followed by a validation with 11 independent cohorts (n = 1,945) identifies BCMA as a novel druggable target. Finally, linear regression modeling identifies major determinants of tumor immunogenicity, which include well-characterized modulators as well as a novel candidate, CCR8, which is then tested in an orthologous immunodeficient mouse model.

Conclusions
The immunophenotypes of the tumors and the cancer antigenome remain widely unexplored, and our findings represent a step toward the development of personalized cancer immunotherapies.
An approach for determining and measuring network hierarchy applied to comparing the phosphorylome and the regulome
Authors: Cheng Chao , Andrews Erik , Yan Koon-Kiu , Ung Matthew , Wang Daifeng , Gerstein Mark 
Published: March 2015

AbstractMany biological networks naturally form a hierarchy with a preponderance of downward information flow. In this study, we define a score to quantify the degree of hierarchy in a network and develop a simulated-annealing algorithm to maximize the hierarchical score globally over a network. We apply our algorithm to determine the hierarchical structure of the phosphorylome in detail and investigate the correlation between its hierarchy and kinase properties. We also compare it to the regulatory network, finding that the phosphorylome is more hierarchical than the regulome.
High-resolution genomic analysis: the tumor-immune interface comes into focus
Authors: Havel Jonathan J , Chan Timothy A 
Published: March 2015

AbstractA genomic analysis of heterogeneous colorectal tumor samples has uncovered interactions between immunophenotype and various aspects of tumor biology, with implications for informing the choice of immunotherapies for specific patients and guiding the design of personalized neoantigen-based vaccines.Please see related article: http://dx.doi.org/10.1186/s13059-015-0620-6
Single-cell analysis of lung adenocarcinoma cell lines reveals diverse expression patterns of individual cells invoked by a molecular target drug treatment
Authors: Suzuki Ayako , Matsushima Koutatsu , Makinoshima Hideki , Sugano Sumio , Kohno Takashi , Tsuchihara Katsuya , Suzuki Yutaka 
Published: March 2015

Abstract
Background
To understand the heterogeneous behaviors of individual cancer cells, it is essential to investigate gene expression levels as well as their divergence between different individual cells. Recent advances in next-generation sequencing-related technologies have enabled us to conduct a single-cell RNA-Seq analysis of a series of lung adenocarcinoma cell lines.

Results
We analyze a total of 336 single-cell RNA-Seq libraries from seven cell lines. The results are highly robust regarding both average expression levels and the relative gene expression differences between individual cells. Gene expression diversity is characteristic depending on genes and pathways. Analyses of individual cells treated with the multi-tyrosine kinase inhibitor vandetanib reveal that, while the ribosomal genes and many other so-called house-keeping genes reduce their relative expression diversity during the drug treatment, the genes that are directly targeted by vandetanib, the EGFR and RET genes, remain constant. Rigid transcriptional control of these genes may not allow plastic changes of their expression with the drug treatment or during the cellular acquisition of drug resistance. Additionally, we find that the gene expression patterns of cancer-related genes are sometimes more diverse than expected based on the founder cells. Furthermore, we find that this diversity is occasionally latent in a normal state and initially becomes apparent after the drug treatment.

Conclusions
Characteristic patterns in gene expression divergence, which would not be revealed by transcriptome analysis of bulk cells, may also play important roles when cells acquire drug resistance, perhaps by providing a cellular reservoir for gene expression programs.
Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease
Authors: Morgan Xochitl C , Kabakchiev Boyko , Waldron Levi , Tyler Andrea D , Tickle Timothy L , Milgrom Raquel , Stempak Joanne M , Gevers Dirk , Xavier Ramnik J , Silverberg Mark S , Huttenhower Curtis 
Published: March 2015

Abstract
Background
Pouchitis is common after ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC). Similar to inflammatory bowel disease (IBD), both host genetics and the microbiota are implicated in its pathogenesis. We use the IPAA model of IBD to associate mucosal host gene expression with mucosal microbiomes and clinical outcomes. We analyze host transcriptomic data and 16S rRNA gene sequencing data from paired biopsies from IPAA patients with UC and familial adenomatous polyposis. To achieve power for a genome-wide microbiome-transcriptome association study, we use principal component analysis for transcript and clade reduction, and identify significant co-variation between clades and transcripts.

Results
Host transcripts co-vary primarily with biopsy location and inflammation, while microbes co-vary primarily with antibiotic use. Transcript-microbe associations are surprisingly modest, but the most strongly microbially-associated host transcript pattern is enriched for complement cascade genes and for the interleukin-12 pathway. Activation of these host processes is inversely correlated with Sutterella, Akkermansia, Bifidobacteria, and Roseburia abundance, and positively correlated with Escherichia abundance.

Conclusions
This study quantifies the effects of inflammation, antibiotic use, and biopsy location upon the microbiome and host transcriptome during pouchitis. Understanding these effects is essential for basic biological insights as well as for well-designed and adequately-powered studies. Additionally, our study provides a method for profiling host-microbe interactions with appropriate statistical power using high-throughput sequencing, and suggests that cross-sectional changes in gut epithelial transcription are not a major component of the host-microbiome regulatory interface during pouchitis.
ClinSeK: a targeted variant characterization framework for clinical sequencing
Authors: Zhou Wanding , Zhao Hao , Chong Zechen , Mark Routbort J , Eterovic Agda K , Meric-Bernstam Funda , Chen Ken 
Published: March 2015

AbstractApplying genomics to patient care demands sensitive, unambiguous and rapid characterization of a known set of clinically relevant variants in patients’ samples, an objective substantially different from the standard discovery process, in which every base in every sequenced read must be examined. Further, the approach must be sufficiently robust as to be able to detect multiple and potentially rare variants from heterogeneous samples. To meet this critical objective, we developed a novel variant characterization framework, ClinSeK, which performs targeted analysis of relevant reads from high-throughput sequencing data. ClinSeK is designed for efficient targeted short read alignment and is capable of characterizing a wide spectrum of genetic variants from single nucleotide variation to large-scale genomic rearrangement breakpoints. Applying ClinSeK to over a thousand cancer patients demonstrated substantively better performance, in terms of accuracy, runtime and disk storage, for clinical applications than existing variant discovery tools. ClinSeK is freely available for academic use at http://bioinformatics.mdanderson.org/main/clinsek.
The gut microbiome in cardio-metabolic health
Authors: Hansen Tue H , Gøbel Rikke J , Hansen Torben , Pedersen Oluf 
Published: March 2015

AbstractWith the prevalence of cardio-metabolic disorders reaching pandemic proportions, the search for modifiable causative factors has intensified. One such potential factor is the vast microbial community inhabiting the human gastrointestinal tract, the gut microbiota. For the past decade evidence has accumulated showing the association of distinct changes in gut microbiota composition and function with obesity, type 2 diabetes and cardiovascular disease. Although causality in humans and the pathophysiological mechanisms involved have yet to be decisively established, several studies have demonstrated that the gut microbiota, as an environmental factor influencing the metabolic state of the host, is readily modifiable through a variety of interventions. In this review we provide an overview of the development of the gut microbiome and its compositional and functional changes in relation to cardio-metabolic disorders, and give an update on recent progress in how this could be exploited in microbiota-based therapeutics.