bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL1RN Variation Influences Both Disease Susceptibility and Response to Recombinant Human Interleukin‐1 Receptor Antagonist Therapy in Systemic Juvenile Idiopathic Arthritis
Authors: Arthur Victoria L. , Shuldiner Emily , Remmers Elaine F. , Hinks Anne , Grom Alexei A. , Foell Dirk , Martini Alberto , Gattorno Marco , Özen Seza , Prahalad Sampath , Zeft Andrew S. , Bohnsack John F. , Ilowite Norman T. , Mellins Elizabeth D. , Russo Ricardo , Len Claudio , Oliveira Sheila , Yeung Rae S. M. , Rosenberg Alan M. , Wedderburn Lucy R. , Anton Jordi , Haas Johannes‐Peter , Rösen‐Wolff Angela , Minden Kirsten , Szymanski Ann Marie ,   INCHARGE Consortium, Thomson Wendy , Kastner Daniel L. , Woo Patricia , Ombrello Michael J. 
Published: April 2018

ObjectiveTo determine whether systemic juvenile idiopathic arthritis (JIA) susceptibility loci that were identified by candidate gene studies demonstrate association with systemic JIA in the largest study population assembled to date.MethodsSingle‐nucleotide polymorphisms (SNPs) from 11 previously reported systemic JIA risk loci were examined for association in 9 populations, including 770 patients with systemic JIA and 6,947 controls. The effect of systemic JIA–associated SNPs on gene expression was evaluated in silico in paired whole genome and RNA sequencing data from the lymphoblastoid cell lines (LCLs) of 373 European subjects from the 1000 Genomes Project. Responses of systemic JIA–associated SNPs to anakinra treatment were evaluated in 38 US patients for whom treatment response data were available.ResultsWe found no association between the previously reported 26 SNPs and systemic JIA. Expanded analysis of the regions containing the 26 SNPs revealed only 1 significant association: the promoter region of IL1RN (P < 1 × 10–4). Systemic JIA–associated SNPs correlated with IL1RN expression in LCLs, with an inverse correlation between systemic JIA risk and IL1RN expression. The presence of homozygous IL1RN high expression alleles correlated strongly with a lack of response to anakinra therapy (odds ratio 28.7 [95% confidence interval 3.2–255.8]).ConclusionIn our study, IL1RN was the only candidate locus associated with systemic JIA. The implicated SNPs are among the strongest known determinants of IL1RN and interleukin‐1 receptor antagonist levels, linking low expression with increased systemic JIA risk. Homozygous high expression alleles predicted nonresponsiveness to anakinra therapy, making them ideal candidate biomarkers to guide systemic JIA treatment. This study is an important first step toward the personalized treatment of systemic JIA.
A real‐time fluorescence assay for protease activity and inhibitor screening based on the aggregation‐caused quenching of a perylene probe
Authors: Wang Yan , Zhang Zhifang , Zhang Ya , Yu Cong 
Published: April 2018

AbstractWe have established a real‐time and label‐free fluorescence turn‐on strategy for protease activity detection and inhibitor screening via peptide‐induced aggregation‐caused quenching of a perylene probe. Because of electrostatic interactions and high hydrophilicity, poly‐l‐glutamic acid sodium salt (PGA; a negatively charged peptide) could induce aggregation of a positively charged perylene probe (probe 1) and the monomer fluorescence of probe 1 was effectively quenched. After a protease was added, PGA was enzymatically hydrolyzed into small fragments and probe 1 disaggregated. The fluorescence recovery of probe 1 was found to be proportional to the concentration of protease in the range from 0 to 1 mU/ml. The detection limit was down to 0.1 mU/ml. In the presence of a protease inhibitor, protease activity was inhibited and fluorescence recovery reduced. Moreover, we demonstrated the potential application of our method in a complex mixture sample including 1% human serum. Our method is simple, fast and cost effective.
Pretreatment subcutaneous adipose tissue predicts the outcomes of patients with head and neck cancer receiving definitive radiation and chemoradiation in Taiwan
Authors: Pai Ping Ching , Chuang Chi Cheng , Chuang Wen Ching , Tsang Ngan Ming , Tseng Chen Kan , Chen Kuan Hung , Yen Tzu Chen , Lin Chien Yu , Chang Kai Ping , Lei Kin Fong 
Published: April 2018

AbstractWe aimed to determine whether body composition assessment before treatment can predict outcomes in patients with head and neck cancer (HNC). All 881 patients with locoregional head and neck cancer treated with curative intent radiotherapy (RT) between 2005 and 2012 were retrospectively investigated. Body composition was analyzed via pre‐RT planning computed tomography (CT) images. Subcutaneous adipose tissue (SAT) and skeletal muscle (SM) indices were measured cross‐sectionally at the level of the third thoracic vertebra. Overall survival (OS), locoregional control (LRC), and distant metastasis‐free survival (MFS) were analyzed by body composition index and body mass index (BMI). Survivors were followed up for a median of 4.68 years. The SAT indices in female patients were significantly higher than those in males (P < 0.001). The median SAT and muscle indices were 18.6 and 34.3 cm2/m2 for women and 6.19 and 51.74 cm2/m2 for men, respectively. The 5‐ and 10‐year MFS, LRC, and OS rates were 83% and 82.1%, 73.4% and 71.4%, and 66.4 and 57.6%, respectively. Higher pretreatment SAT index was associated with MFS (hazard ratio [HR]: 0.65; P = 0.015), LRC (HR: 0.758; P = 0.047), and OS (HR: 0.604; P < 0.001). Higher pretreatment BMI was associated with MFS (HR: 0.642; P = 0.031) and OS (HR: 0.615; P < 0.001). The pretreatment SM index had no significant effect on MFS, LRC, and OS. Multivariate analysis revealed that T‐stage, N‐stage, lesion sites, age, and RT treatment days are independent factors associated with OS; T‐stage, N‐stage, and lesion sites are independent factors associated with MFS; and N‐stage, smoking history, and betel quid chewing history are independent factors associated with LRC. A higher CT‐assessed SAT index predicts superior MSF, LCR, and OS in patients with curative HNC, whereas SM does not predict survival or locoregional control.
Aging‐related prognosis analysis of definitive radiotherapy for very elderly esophageal cancer
Authors: Zhou Yong‐Chun , Chen Li‐Li , Xu Hong‐Bo , Sun Qian , Zhang Qi , Cai Han‐Fei , Jiang Hao 
Published: April 2018

AbstractBecause of the exclusion for the patients more than 75 years (very elderly patients) in many clinical trials of esophageal cancer (EC), there is no consensus on prognosis and treatment for this population. We aim to evaluate the outcomes and aging‐related prognostic factors of definitive radiotherapy (RT) for very elderly EC patients. We retrospectively analyzed 149 very elderly EC patients consecutively treated between January 2015 and June 2016 by definitive intensity‐modulated radiotherapy (IMRT) with or without chemotherapy. The clinical outcome and toxicities were assessed, and the potential prognostic factors, such as nutritional risk index (NRI) and neutrophil–lymphocyte ratio (NLR), were analyzed statistically. The median follow‐up time for survivors was 22.5 months. The 2‐year overall survival (OS), local–regional failure‐free survival (LRFFS), and distant metastasis‐free survival (DMFS) were 51.6%, 54.7%, and 85.2%, respectively. Independent predictors for poorer OS were higher American Joint Committee on Cancer (AJCC) stage, lower NRI, and higher NLR value before RT. Meanwhile, the total dose (cutoff value 60 Gy) of planning gross tumor volume (PGTV) and chemotherapy was also identified as independent prognostic indicator for LRFFS and DMFS, respectively. 72 patients had treatment failure and 58 (80.6%), 6 (8.3%), and 18 (25.0%) patients had experienced local, regional, and distant failure, respectively. Few severe toxicities were observed. The conservative definitive RT with modern technique was effective for very elderly EC patients in short term with low rate and tolerable toxicities. Local residue or recurrence was the most common failure pattern. The aging‐related prognostic factors concerned nutrition and immune, such as NRI and NLR before RT, should be considered for use in future clinical practice.
Cervical lymph node carcinoma metastasis from unknown primary site: a retrospective analysis of 154 patients
Authors: Wang Yan , He Sha‐Sha , Bao Yong , Cai Xiu‐Yu , Chen Hai‐Yang , Yang Xing‐Li , Chen Dan‐Ming , Lu Li‐Xia , Chen Yong 
Published: April 2018

AbstractDespite advances in diagnosis and treatment, the existence of cervical lymph node carcinoma of unknown primary site (CCUP) has always been an urgent problem worldwide. There is still no consensus on the optimal management for CCUP. In this retrospective review, we analyze the clinical characteristics of CCUP patients treated at our institution and examine how these characteristics and treatments were associated with survival. Clinicopathologic features, treatments, and survival outcomes of 154 CCUP patients were collected from the hospital records and analyzed. Survival was estimated by Kaplan–Meier methods and compared by the log‐rank test. Cox proportional hazards regression analysis was used to assess the factors independently associated with overall survival (OS) and progression‐free survival (PFS). Median follow‐up period was 26.44 months (range, 0.53–146.53 months). Multivariate analysis showed N stage, pathologic type, and lymph node extranodal extension (ENE) to be independent prognostic factors for OS in CCUP patients, but not PFS. Subgroup analysis of patients who received radiotherapy showed that radiotherapy to the pharyngeal mucosa was associated with better OS (P = 0.045), but not with better PFS. Advanced N stage, nonsquamous cell carcinoma, and lymph node ENE predict poor prognosis in patients with CCUP. In addition, radiotherapy to suspicious mucosa is accompanied by better OS. These study findings should be useful to clinicians when selecting the treatment approach.
The direct and indirect association of cervical microbiota with the risk of cervical intraepithelial neoplasia
Authors: Zhang Chaoting , Liu Ying , Gao Weijiao , Pan Yaqi , Gao Yunong , Shen Jing , Xiong Hongchao 
Published: April 2018

AbstractCervical microbiota composition is associated with cervical HPV infection and CIN severity. Previous studies only assessed the total association between cervical microbiota and HPV infections or CINs, and yet no study reported the direct and indirect associations between cervical microbiota and CINs mediated by HPV infection, respectively. The aim of this study was to investigate the direct and indirect associations between microbiotas and CIN severity. Cervical microbiota of 126 women with CIN 1− (normal cytology and CIN 1) and 40 with CIN 2+ (CIN 2 and CIN 3) were analyzed using Illumina sequencing based on the 16S rRNA gene. HPV was detected using a highly sensitive PCR primer set (SPF1/GP6+). Indirect effects of Pseudomonas stutzeri, Bacteroides fragilis, Lactobacillus delbrueckii, Atopobium vaginae, and Streptococcus agalactiae mediated by HPV infection on CIN status were observed. The directions of the direct and the indirect associations between CIN status and Ps. stutzeri were opposite. The directions of the direct and the indirect associations between CIN status and A. vaginae were the same. B. fragilis, L. delbrueckii, and S. agalactiae only had indirect association with CIN status. In summary, our study provided suggestive evidence that some microbial populations could have direct or indirect effects mediated by affecting HPV infection on CIN progression. Besides HPV infection, microbial community composition possibly plays a role in cervical carcinogenesis.
Alkynylnicotinamide‐Based Compounds as ABL1 Inhibitors with Potent Activities against Drug‐Resistant CML Harboring ABL1(T315I) Mutant Kinase
Authors: Larocque Elizabeth A. , Naganna N. , Opoku‐Temeng Clement , Lambrecht Alyssa M. , Sintim Herman O. 
Published: April 2018

AbstractThe introduction of imatinib into the clinical scene revolutionized the treatment of chronic myelogenous leukemia (CML). The overall eight‐year survival rate for CML has increased from about 6 % in the 1970s to over 90 % in the imatinib era. However, about 20 % of CML patients harbor primary or acquired resistance to tyrosine kinase inhibitors. ABL1 point mutations in the BCR‐ABL1 fusion protein, such as ABL1(T315I), typically emerge after prolonged kinase inhibitor treatment. Ponatinib (AP24534) is currently the only approved CML drug that is active against the ABL1(T315I) mutation. However, ponatinib has severe cardiovascular toxicities; hence, there have been efforts to find safer CML drugs that work against ABL1 secondary mutations. We reveal that isoquinoline‐ or naphthyridine‐based compounds, such as HSN431, HSN576, HSN459, and HSN608 potently inhibit the enzymatic activities of ABL1, ABL1(T315I), and ABL1(E255K). These compounds inhibit the proliferation of ABL1‐driven CML cell lines, K652 and KCL22 as well as the drug‐resistant cell line, KCL22‐IR, which harbors the secondary mutated ABL1(T315I) kinase.
Message‐Passing Algorithms for Synchronization Problems over Compact Groups
Authors: Perry Amelia , Wein Alexander S. , Bandeira Afonso S. , Moitra Ankur 
Published: April 2018

AbstractVarious alignment problems arising in cryo‐electron microscopy, community detection, time synchronization, computer vision, and other fields fall into a common framework of synchronization problems over compact groups such as ℤ/L, U(1), or SO(3). The goal in such problems is to estimate an unknown vector of group elements given noisy relative observations. We present an efficient iterative algorithm to solve a large class of these problems, allowing for any compact group, with measurements on multiple “frequency channels” (Fourier modes, or more generally, irreducible representations of the group). Our algorithm is a highly efficient iterative method following the blueprint of approximate message passing (AMP), which has recently arisen as a central technique for inference problems such as structured low‐rank estimation and compressed sensing. We augment the standard ideas of AMP with ideas from representation theory so that the algorithm can work with distributions over general compact groups. Using standard but nonrigorous methods from statistical physics, we analyze the behavior of our algorithm on a Gaussian noise model, identifying phases where we believe the problem is easy, (computationally) hard, and (statistically) impossible. In particular, such evidence predicts that our algorithm is information‐theoretically optimal in many cases, and that the remaining cases exhibit statistical‐to‐computational gaps. © 2018 Wiley Periodicals, Inc.
Our use, misuse, and abandonment of a concept: Whither habitat?
Authors: Kirk David Anthony , Park Allysia C. , Smith Adam C. , Howes Briar J. , Prouse Brigid K. , Kyssa Naschelly G. , Fairhurst Elizabeth N. , Prior Kent A. 
Published: April 2018

SummaryThe foundational concept of habitat lies at the very root of the entire science of ecology, but inaccurate use of the term compromises scientific rigor and communication among scientists and nonscientists. In 1997, Hall, Krausman & Morrison showed that ‘habitat’ was used correctly in only 55% of articles. We ask whether use of the term has been more accurate since their plea for standardization and whether use varies across the broader range of journals and taxa in the contemporary literature (1998–2012). We searched contemporary literature for ‘habitat’ and habitat‐related terms, ranking usage as either correct or incorrect, following a simplified version of Hall et al.'s definitions. We used generalized linear models to compare use of the term in contemporary literature with the papers reviewed by Hall et al. and to test the effects of taxa, journal impact in the contemporary articles and effects due to authors that cited Hall et al. Use of the term ‘habitat’ has not improved; it was still only used correctly about 55% of the time in the contemporary data. Proportionately more correct uses occurred in articles that focused on animals compared to ones that included plants, and papers that cited Hall et al. did use the term correctly more often. However, journal impact had no effect. Some habitat terms are more likely to be misused than others, notably ‘habitat type’, usually used to refer to vegetation type, and ‘suitable habitat’ or ‘unsuitable habitat’, which are either redundant or nonsensical by definition. Inaccurate and inconsistent use of the term can lead to (1) misinterpretation of scientific findings; (2) inefficient use of conservation resources; (3) ineffective identification and prioritization of protected areas; (4) limited comparability among studies; and (5) miscommunication of science‐based findings. Correct usage would improve communication with scientists and nonscientists, thereby benefiting conservation efforts, and ecology as a science.
Tree seed rain and seed removal, but not the seed bank, impede forest recovery in bracken (Pteridium aquilinum (L.) Kuhn)‐dominated clearings in the African highlands
Authors: Ssali Fredrick , Moe Stein R. , Sheil Douglas 
Published: April 2018

AbstractConsiderable areas dominated by bracken Pteridium aquilinum (L.) Kuhn occur worldwide and are associated with arrested forest recovery. How forest recovery is impeded in these areas remains poorly understood, especially in the African highlands. The component processes that can lead to recruitment limitation—including low seed arrival, availability and persistence—are important determinants of plant communities and offer a potential explanation for bracken persistence. We investigated key processes that can contribute to recruitment limitation in bracken‐dominated clearings in the Bwindi Impenetrable National Park, Uganda. We examined if differences in seed rain (dispersal limitation), soil seed bank, or seed removal (seed viability and persistence) can, individually or in combination, explain the differences in tree regeneration found between bracken‐dominated areas and the neighboring forest. These processes were assessed along ten 50‐m transects crossing the forest–bracken boundary. When compared to the neighboring forest, bracken clearings had fewer seedlings (bracken 11,557 ± 5482 vs. forest 34,515 ± 6066 seedlings/ha), lower seed rain (949 ± 582 vs. 1605 ± 335 tree seeds m−2 year−1), comparable but sparse soil seed bank (304 ± 236 vs. 264 ± 99 viable tree seeds/m2), higher seed removal (70.1% ± 2.4% vs. 40.6% ± 2.4% over a 3‐day interval), and markedly higher rodent densities (25.7 ± 5.4 vs. 5.0 ± 1.6 rodents per 100 trapping sessions). Camera traps revealed that rodents were the dominant animals visiting the seeds in our seed removal study. Synthesis: Recruitment limitation contributes to both the slow recovery of forest in bracken‐dominated areas, and to the composition of the tree species that occur. Low seed arrival and low persistence of unburied seeds can both explain the reduced density of seedlings found in bracken versus neighboring forest. Seed removal, likely due to rodents, in particular appears sufficient to constrain forest recovery and impacts some species more severely than others.
An evaluation of government‐recommended stocking systems for sustaining pastoral businesses and ecosystems of the Alpine Meadows of the Qinghai‐Tibetan Plateau
Authors: Wang Yingxin , Hodgkinson Kenneth C. , Hou Fujiang , Wang Zhaofeng , Chang Shenghua 
Published: April 2018

AbstractChina introduced the “Retire Livestock and Restore Grassland” policy in 2003. It was strengthened in 2011 by additional funding for on‐farm structures. On the Qinghai‐Tibetan Plateau (QTP), fences were erected, livestock excluded from degraded areas, rotational stocking introduced, nighttime shelters were built, forages grown, and seed sown. However, the effectiveness of these actions and their value to Tibetan herders has been questioned. We conducted a sheep stocking experiment for 5 years in an Alpine Meadow region of the QTP to evaluate stocking options recommended by Government. Cold and warm season stocking each at three rates (0, 8, and 16 sheep/ha) and continuous stocking at 0 and 4 sheep/ha were compared. We measured live weights of sheep, plant species richness and evenness, root biomass and carbon (C), nitrogen (N) and phosphorus (P) contents of the 0–10 cm of soil. We found that resting grassland from stocking during the warm season for later cold season stocking significantly reduced plant species richness and evenness and root biomass but not soil C, N, and P. During cold season stocking, live weights of sheep declined whether at a stocking rate of 8 or 16 per ha. In contrast, sheep continuously stocked on grassland at 4 per ha gained weight throughout both the warm and cold seasons and plant species richness and evenness were maintained. Warm season stocking at 8 and 16 sheep/ha increased plant species richness and root biomass but reduced plant species evenness. Resting these alpine grasslands from stocking in the warm season has adverse consequences for plant conservation. Fencing from stocking in the warm season is not justified by this study; all grassland should be judiciously stocked during the warm season to maintain plant species richness. Neither resting nor stocking during the cold season appears to have any adverse consequences but sheltering and in‐door feeding of sheep during the cold season may be more profitable than cold season stocking with use of open nighttime yards.
Identifying important conservation areas for the clouded leopard Neofelis nebulosa in a mountainous landscape: Inference from spatial modeling techniques
Authors: Penjor Ugyen , Macdonald David W. , Wangchuk Sonam , Tandin Tandin , Tan Cedric Kai Wei 
Published: April 2018

AbstractThe survival of large carnivores is increasingly precarious due to extensive human development that causes the habitat loss and fragmentation. Habitat selection is influenced by anthropogenic as well as environmental factors, and understanding these relationships is important for conservation management. We assessed the environmental and anthropogenic variables that influence site use of clouded leopard Neofelis nebulosa in Bhutan, estimated their population density, and used the results to predict the species’ site use across Bhutan. We used a large camera‐trap dataset from the national tiger survey to estimate for clouded leopards, for the first time in Bhutan, (1) population density using spatially explicit capture–recapture models and (2) site‐use probability using occupancy models accounting for spatial autocorrelation. Population density was estimated at (0.10 SD) and (0.12 SE) per 100 km2. Clouded leopard site use was positively associated with forest cover and distance to river while negatively associated with elevation. Mean site‐use probability (from the Bayesian spatial model) was (0.076 SD). When spatial autocorrelation was ignored, the probability of site use was overestimated, (0.066 SD). Predictive mapping allowed us to identify important conservation areas and priority habitats to sustain the future of these elusive, ambassador felids and associated guilds. Multiple sites in the south, many of them outside of protected areas, were identified as habitats suitable for this species, adding evidence to conservation planning for clouded leopards in continental South Asia.