bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome of ‘Ca. Desulfovibrio trichonymphae’, an H2-oxidizing bacterium in a tripartite symbiotic system within a protist cell in the termite gut
Authors: Kuwahara Hirokazu , Yuki Masahiro , Izawa Kazuki , Ohkuma Moriya , Hongoh Yuichi 
Published: November 2016

Abstract
The cellulolytic protist Trichonympha agilis in the termite gut permanently hosts two symbiotic bacteria, ‘Candidatus Endomicrobium trichonymphae’ and ‘Candidatus Desulfovibrio trichonymphae’. The former is an intracellular symbiont, and the latter is almost intracellular but still connected to the outside via a small pore. The complete genome of ‘Ca. Endomicrobium trichonymphae’ has previously been reported, and we here present the complete genome of ‘Ca. Desulfovibrio trichonymphae’. The genome is small (1 410 056 bp), has many pseudogenes, and retains biosynthetic pathways for various amino acids and cofactors, which are partially complementary to those of ‘Ca. Endomicrobium trichonymphae’. An amino acid permease gene has apparently been transferred between the ancestors of these two symbionts; a lateral gene transfer has affected their metabolic capacity. Notably, ‘Ca. Desulfovibrio trichonymphae’ retains the complex system to oxidize hydrogen by sulfate and/or fumarate, while genes for utilizing other substrates common in desulfovibrios are pseudogenized or missing. Thus, ‘Ca. Desulfovibrio trichonymphae’ is specialized to consume hydrogen that may otherwise inhibit fermentation processes in both T. agilis and ‘Ca. Endomicrobium trichonymphae’. The small pore may be necessary to take up sulfate. This study depicts a genome-based model of a multipartite symbiotic system within a cellulolytic protist cell in the termite gut.
Estimating economic losses to tourism in Africa from the illegal killing of elephants
Authors: Naidoo Robin , Fisher Brendan , Manica Andrea , Balmford Andrew 
Published: November 2016

AbstractRecent surveys suggest tens of thousands of elephants are being poached annually across Africa, putting the two species at risk across much of their range. Although the financial motivations for ivory poaching are clear, the economic benefits of elephant conservation are poorly understood. We use Bayesian statistical modelling of tourist visits to protected areas, to quantify the lost economic benefits that poached elephants would have delivered to African countries via tourism. Our results show these figures are substantial (∼USD $25 million annually), and that the lost benefits exceed the anti-poaching costs necessary to stop elephant declines across the continent’s savannah areas, although not currently in the forests of central Africa. Furthermore, elephant conservation in savannah protected areas has net positive economic returns comparable to investments in sectors such as education and infrastructure. Even from a tourism perspective alone, increased elephant conservation is therefore a wise investment by governments in these regions.
AXL-associated tumor inflammation as a poor prognostic signature in chemotherapy-treated triple-negative breast cancer patients
Authors: Bottai Giulia , Raschioni Carlotta , Székely Borbála , Di Tommaso Luca , Szász Attila M , Losurdo Agnese , Győrffy Balázs , Ács Balázs , Torrisi Rosalba , Karachaliou Niki , Tőkés Tímea , Caruso Michele , Kulka Janina , Roncalli Massimo , Santoro Armando , Mantovani Alberto , Rosell Rafael , Reis-Filho Jorge S , Santarpia Libero 
Published: November 2016

AbstractA subgroup of triple-negative breast cancer (TNBC) shows epithelial-to-mesenchymal transition (EMT) features, which are sustained by the interaction between cancer cells and tumor-associated macrophages (TAMs). In this study, the clinical relevance of 30 EMT-related kinases and the potential cross-talk with TAMs were investigated in a cohort of 203 TNBC patients treated with adjuvant chemotherapy. The prognostic value of the evaluated markers was validated in two independent cohorts of TNBC patients treated with adjuvant chemotherapy (N=95; N=137). In vitro, we investigated the potential synergism between cancer cells and TAMs. We found that the EMT-related kinase AXL showed the highest correlation with the frequency of CD163-positive macrophages (rS=0.503; P<0.0001). Relapsing TNBC patients presented high expression of AXL (P<0.0001) and CD163 (P<0.018), but only AXL retained independent prognostic significance in multivariate analysis (relapse-free survival, P=0.002; overall survival P=0.001). In vitro analysis demonstrated that AXL-expressing TNBC cells were able to polarize human macrophages towards an M2-like phenotype, and modulate a specific pattern of pro-tumor cytokines and chemokines. Selective AXL inhibition impaired the activity of M2-like macrophages, reducing cancer cell invasiveness, and restoring the sensitivity of breast cancer cells to chemotherapeutic drugs. These data suggest that the EMT-related kinase AXL overexpressed in cancer cells has prognostic significance, and contributes to the functional skewing of macrophage functions in TNBC. AXL inhibition may represent a novel strategy to target cancer cells, as well as tumor-promoting TAMs in TNBC.
Analysis of induced pluripotent stem cells carrying 22q11.2 deletion
Authors: Toyoshima M , Akamatsu W , Okada Y , Ohnishi T , Balan S , Hisano Y , Iwayama Y , Toyota T , Matsumoto T , Itasaka N , Sugiyama S , Tanaka M , Yano M , Dean B , Okano H , Yoshikawa T 
Published: November 2016

AbstractGiven the complexity and heterogeneity of the genomic architecture underlying schizophrenia, molecular analyses of these patients with defined and large effect-size genomic defects could provide valuable clues. We established human-induced pluripotent stem cells from two schizophrenia patients with the 22q11.2 deletion (two cell lines from each subject, total of four cell lines) and three controls (total of four cell lines). Neurosphere size, neural differentiation efficiency, neurite outgrowth, cellular migration and the neurogenic-to-gliogenic competence ratio were significantly reduced in patient-derived cells. As an underlying mechanism, we focused on the role of DGCR8, a key gene for microRNA (miRNA) processing and mapped in the deleted region. In mice, Dgcr8 hetero-knockout is known to show a similar phenotype of reduced neurosphere size (Ouchi et al., 2013). The miRNA profiling detected reduced expression levels of miRNAs belonging to miR-17/92 cluster and miR-106a/b in the patient-derived neurospheres. Those miRNAs are reported to target p38α, and conformingly the levels of p38α were upregulated in the patient-derived cells. p38α is known to drive gliogenic differentiation. The inhibition of p38 activity by SB203580 in patient-derived neurospheres partially restored neurogenic competence. Furthermore, we detected elevated expression of GFAP, a gliogenic (astrocyte) marker, in postmortem brains from schizophrenia patients without the 22q11.2 deletion, whereas inflammation markers (IL1B and IL6) remained unchanged. In contrast, a neuronal marker, MAP2 expressions were decreased in schizophrenia brains. These results suggest that a dysregulated balance of neurogenic-to-gliogenic competence may underlie neurodevelopmental disorders such as schizophrenia.
A survey of cervical screening among refugee and non‐refugee African immigrant women in Brisbane, Australia
Authors: Anaman Judith A. , Correa‐Velez Ignacio , King Julie 
Published: November 2016

Issue addressedTo compare the level of cervical screening uptake between refugee and non‐refugee African immigrant women living in Brisbane, Australia, and examine factors associated with Pap smear testing.MethodsCross‐sectional survey with a convenience sample of 254 women aged 21–62 years from 22 African countries (144 refugees, 110 non‐refugees). Chi‐square tests were used to compare the demographic and health‐related characteristics between refugee and non‐refugee women. Bivariate and multiple logistic regression analyses were used to assess the relationship between the outcome variable (Pap smear testing) and the independent variables.ResultsTwo‐thirds of women had used Pap smear services in Australia. Chi‐square test analysis established that non‐refugee women were significantly more likely to have used Pap smear services than refugee women (73.6% vs 61.8% respectively; P = 0.047). Immigration status, however, was not a significant predictor of cervical screening uptake in the multiple regression analyses. The significant predictors for screening uptake in these analyses were work arrangement, parity, healthcare visit, knowledge about Pap smear and perceived susceptibility to cervical cancer.ConclusionMost women relied on opportunistic screening after receiving invitation letters to screen or after visiting health professionals for antenatal or postnatal care.So what?The findings suggest that organised cervical screening programs are not reaching most African immigrant women living in Brisbane. It is incumbent on the public health sector, including healthcare professionals and settlement agencies working with African communities, to develop health promotion strategies that meaningfully engage African immigrant women, including those from refugee backgrounds, to enhance their knowledge about cervical cancer and screening practices.
PTPN22 contributes to exhaustion of T lymphocytes during chronic viral infection
Authors: Maine Christian J. , Teijaro John R. , Marquardt Kristi , Sherman Linda A. 
Published: November 2016

SignificanceSome viruses, including lymphocytic choriomeningitis virus clone 13, shut down the ability of CD4 T lymphocytes to produce IL-2, a cytokine required for the survival and function of T lymphocytes. This shutdown contributes to exhaustion of CD4 and CD8 T lymphocytes and chronic viral infection of the host. The underlying mechanism responsible for the loss of cytokine production by CD4 T cells remains poorly understood. We demonstrate that the expression of a protein tyrosine phosphatase, PTPN22, contributes to chronic viral infection. PTPN22 increases the production of IFN-β following infection, resulting in increased expression of the cAMP response element modulator (CREM) in CD4 T lymphocytes. CREM prevents production of IL-2, thereby contributing to T-cell exhaustion and chronic viral infection.
Online social integration is associated with reduced mortality risk
Authors: Hobbs William R. , Burke Moira , Christakis Nicholas A. , Fowler James H. 
Published: November 2016

Significance
People who have stronger social networks live longer. However, can we say the same about online social networks? Here, we conduct such a study. Using public California vital records, we compare 12 million Facebook users to nonusers. More importantly, we also look within Facebook users to explore how online social interactions—reflecting both online and offline social activity—are associated with longevity. We find that Facebook users who accept more friendships have a lower risk of mortality, but there is no relationship for those who initiate more friendships. Mortality risk is lowest for those with high levels of offline social interaction and moderate levels of online social interaction.
Epigenetic gene regulation by Janus kinase 1 in diffuse large B-cell lymphoma
Authors: Rui Lixin , Drennan Amanda C. , Ceribelli Michele , Zhu Fen , Wright George W. , Huang Da Wei , Xiao Wenming , Li Yangguang , Grindle Kreg M. , Lu Li , Hodson Daniel J. , Shaffer Arthur L. , Zhao Hong , Xu Weihong , Yang Yandan , Staudt Louis M. 
Published: November 2016

Significance
Autocrine cytokine signaling in cancer can activate members of the Janus kinase (JAK) family, which are generally thought to act by phosphorylating STAT family transcription factors. We report here that JAK1 mediates autocrine IL-6 and IL-10 cytokine signaling in activated B-cell–like (ABC) diffuse large B-cell lymphoma (DLBCL) by a noncanonical epigenetic regulatory mechanism involving phosphorylation of histone H3 on tyrosine 41. We have identified target genes that are activated in ABC DLBCL by this epigenetic mechanism. Knowledge of these epigenetic targets led to our demonstration that JAK1 inhibitors synergize with inhibitors of active B cell receptor signaling in ABC DLBCL, suggesting a new therapeutic strategy for this subtype of DLBCL, which is the most difficult to cure with current therapy.
Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells
Authors: Wang Zhongyuan , Li Bo , Zhou Liang , Yu Shubin , Su Zijie , Song Jiaxing , Sun Qi , Sha Ou , Wang Xiaomei , Jiang Wenqi , Willert Karl , Wei Lei , Carson Dennis A. , Lu Desheng 
Published: November 2016

Significance
The Wnt pathway is implicated in multiple cancers, but to date no pharmacologically acceptable Wnt inhibitors have been introduced into the clinic. Analogs of the natural product prodigiosin are in early leukemia trials, but their mechanisms of action have not been established. We report that prodigiosin and its analog obatoclax block Wnt signaling at nanomolar concentrations by preventing the phosphorylation of Dishevelled. Cyclin D is an established target of Wnt signaling, and elevated cyclin D levels are characteristic of advanced breast cancer. In a Wnt-driven murine transgenic model of breast cancer, prodigiosin potently diminished cyclin D levels and blocked the growth of tumors. These results provide a rationale for the introduction of prodigiosin analogs into clinical trials of advanced breast cancer.
QAcon: single model quality assessment using protein structural and contact information with machine learning techniques
Authors: Cao Renzhi , Adhikari Badri , Bhattacharya Debswapna , Sun Miao , Hou Jie , Cheng Jianlin 
Published: November 2016

Abstract

Motivation
Protein model quality assessment (QA) plays a very important role in protein structure prediction. It can be divided into two groups of methods: single model and consensus QA method. The consensus QA methods may fail when there is a large portion of low quality models in the model pool.

Results
In this paper, we develop a novel single-model quality assessment method QAcon utilizing structural features, physicochemical properties, and residue contact predictions. We apply residue-residue contact information predicted by two protein contact prediction methods PSICOV and DNcon to generate a new score as feature for quality assessment. This novel feature and other 11 features are used as input to train a two-layer neural network on CASP9 datasets to predict the quality of a single protein model. We blindly benchmarked our method QAcon on CASP11 dataset as the MULTICOM-CLUSTER server. Based on the evaluation, our method is ranked as one of the top single model QA methods. The good performance of the features based on contact prediction illustrates the value of using contact information in protein quality assessment.

Availability and Implementation
The web server and the source code of QAcon are freely available at: http://cactus.rnet.missouri.edu/QAcon

Supplementary information
Supplementary data are available at Bioinformatics online.
Cost and economic benefit of clinical decision support systems for cardiovascular disease prevention: a community guide systematic review
Authors: Jacob Verughese , Thota Anilkrishna B , Chattopadhyay Sajal K , Njie Gibril J , Proia Krista K , Hopkins David P , Ross Murray N , Pronk Nicolaas P , Clymer John M 
Published: November 2016

Objective: This review evaluates costs and benefits associated with acquiring, implementing, and operating clinical decision support systems (CDSSs) to prevent cardiovascular disease (CVD).
Materials and Methods: Methods developed for the Community Guide were used to review CDSS literature covering the period from January 1976 to October 2015. Twenty-one studies were identified for inclusion.
Results: It was difficult to draw a meaningful estimate for the cost of acquiring and operating CDSSs to prevent CVD from the available studies (n = 12) due to considerable heterogeneity. Several studies (n = 11) indicated that health care costs were averted by using CDSSs but many were partial assessments that did not consider all components of health care. Four cost-benefit studies reached conflicting conclusions about the net benefit of CDSSs based on incomplete assessments of costs and benefits. Three cost-utility studies indicated inconsistent conclusions regarding cost-effectiveness based on a conservative $50,000 threshold.
Discussion: Intervention costs were not negligible, but specific estimates were not derived because of the heterogeneity of implementation and reporting metrics. Expected economic benefits from averted health care cost could not be determined with confidence because many studies did not fully account for all components of health care.
Conclusion: We were unable to conclude whether CDSSs for CVD prevention is either cost-beneficial or cost-effective. Several evidence gaps are identified, most prominently a lack of information about major drivers of cost and benefit, a lack of standard metrics for the cost of CDSSs, and not allowing for useful life of a CDSS that generally extends beyond one accounting period.
Lumpy Hands
Authors: Goldenberg Alina , Jacob Sharon E. 
Published: November 2016

ABSTRACT
Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. In this modality, there is transfer of medical information electronically (including patient history and visual data) on a patient in one location to a provider who is in another location. The construct of this column is such that cases are presented in a standardized teledermatology reader format. This is a case of chronic lumpy growths presenting on both hands.
Perianal Crohn Disease in a Large Multicenter Pediatric Collaborative
Authors: Adler Jeremy , Dong Shiming , Eder Sally J. , Dombkowski Kevin J. ,   ImproveCareNow Pediatric IBD Learning Health System
Published: November 2016

ABSTRACTBackground:Although perianal complications of Crohn disease (CD) are commonly encountered in clinical practice, the epidemiology of perianal CD among populations of children is poorly understood. We sought to characterize the prevalence of perianal disease in a large and diverse population of pediatric patients with CD.Methods:We conducted retrospective analyses from a prospective observational cohort, the ImproveCareNow Network (May 2006–October 2014), a multicenter pediatric inflammatory bowel disease quality improvement collaborative. Clinicians prospectively documented physical examination and phenotype classification at outpatient visits. Perianal examination findings and concomitant phenotype change were used to corroborate time of new‐onset perianal disease. Results were stratified by age, sex, and race and compared across groups with logistic regression. Cumulative incidence was estimated using Kaplan‐Meier analyses and compared between groups with Cox proportional hazard regression models.Results:The registry included 7076 patients with CD (41% girls). Missing/conflicting entries resulted in 397 (6%) patient exclusions. Among the remaining 6679 cases, 1399 (21%) developed perianal disease. Perianal disease was more common among boys (22%) than girls (20%; P = 0.013) and developed sooner after diagnosis among those with later rather than early onset disease (P < 0.001). Perianal disease was also more common among blacks (26%) compared with whites (20%; P = 0.017). Asians with later onset CD developed perianal disease earlier in their disease course (P = 0.01). There was no association between disease location or nutritional status at diagnosis and later development of perianal disease.Conclusions:In this large multicenter collaborative, we found that perianal disease is more common among children with CD than previously recognized. Differences in the development of perianal disease were found across racial and other subgroups. Treatment strategies are needed to prevent perianal disease development.
PD-L1 Expression in Carcinosarcomas of the Gynecologic Tract: A Potentially Actionable Biomarker
Authors: Pinto Andre , Mackrides Nicholas , Nadji Mehrdad 
Published: November 2016

Background:
Carcinosarcomas of the gynecologic tract, also known as malignant mixed Müllerian tumors, are aggressive neoplasms with a high recurrence rate and poor prognosis. Despite advances in adjuvant therapies in recent years, the prognosis of these tumors has not improved. In fact, there are currently no consensus guidelines for the treatment of these neoplasms and the search for targetable biomarkers has not been successful so far. Programmed death-ligand 1 (PD-L1) has emerged as a potential target for therapeutics in a number of malignant tumors, including melanoma, lung, and colorectal cancer. In normal conditions, PD-L1 is thought to promote immune homeostasis via a number of pathways, but mainly through downregulation of cytotoxic T cells. In some human neoplasms, however, overexpression of PD-L1 by tumor cells has been observed, which can modulate the immune system to allow cancer cells to evade host response. As this marker could potentially be a therapeutic target for these tumors, the immunohistochemical expression of PD-L1 in a group of carcinosarcomas was evaluated in the present study.

Material and Methods:
Twenty-nine cases of gynecologic carcinosarcomas were analyzed, corresponding to tumors originating from the uterus (25), ovary (2), fallopian tube (1), and pelvic epithelium (1). Immunohistochemistry for PD-L1 was performed on paraffin sections and the staining results were assessed semiquantitatively in both epithelial and mesenchymal components of each tumor.

Results:
Positive membranous staining for PD-L1 was detected in 25/29 tumors (86%). The epithelial components were strongly positive in 19/29 (65%) and weakly positive in 6/29 tumors (21%). The mesenchymal elements were strongly positive in 8/29 (27%) and weakly positive in 3/29 tumors (10%). With exception of 1, all tumors with positive sarcomatous components had staining of the carcinomatous element. Four tumors were negative for PD-L1 in both components.

Conclusions:
This study shows that PD-L1 is expressed by the majority of carcinosarcomas, predominantly in the epithelial components. This is particularly important as most locoregional recurrences and distant metastases are of epithelial origin. This finding may serve as a basis for possible therapeutic approaches using antibodies that have already shown significant value in a number of other malignant tumors.
Comparison of Transumbilical Laparoscopically Assisted Appendectomy to Conventional Laparoscopic Appendectomy in Children
Authors: Karam Paul A. , Mohan Arathi , Buta Martin R. , Seifarth Federico G. 
Published: November 2016

Purpose:
To compare surgical outcomes of children with appendicitis treated with the transumbilical laparoscopically assisted appendectomy (TULAA) versus the conventional 3-port laparoscopic appendectomy (TPLA).

Materials and Methods:
Retrospective study of pediatric patients with appendicitis treated with TULAA or TPLA between January 2010 and December 2015. Operative time (OT), length of stay, cost, and surgical site infection rate were compared between the 2 groups.

Results:
Six hundred twenty-five appendectomies were performed [263 TULAA, 362 TPLA: acute (457), gangrenous (39), and perforated (129)]. TULAA had a shorter OT (median, 40 vs. 67 min; P<0.001), a shorter length of stay (median, 20 vs. 23 h; P<0.001), and a lesser cost (median $6266 vs. $8927; P<0.001). Surgical site infection rate was slightly higher in the TULAA group (6% vs. 4%; P=0.19).

Conclusions:
TULAA had a shorter OT and was less costly than conventional TPLA. TULAA should be considered as the first surgical approach at treating appendicitis in children.