bluuebunny/crossref_metadata_2025 huggingface dataset:
COADREADx: A comprehensive algorithmic dissection of colorectal cancer unravels salient biomarkers and actionable insights into its discrete progression
Authors: Palaniappan Ashok , Muthamilselvan Sangeetha , Sarathi Arjun
Published: October 2024

Background

Colorectal cancer is a common condition with an uncommon burden of disease, heterogeneity in manifestation, and no definitive treatment in the advanced stages. Renewed efforts to unravel the genetic drivers of colorectal cancer progression are paramount. Early-stage detection contributes to the success of cancer therapy and increases the likelihood of a favorable prognosis. Here, we have executed a comprehensive computational workflow aimed at uncovering the discrete stagewise genomic drivers of colorectal cancer progression.

Methods

Using the TCGA COADREAD expression data and clinical metadata, we constructed stage-specific linear models as well as contrast models to identify stage-salient differentially expressed genes. Stage-salient differentially expressed genes with a significant monotone trend of expression across the stages were identified as progression-significant biomarkers. The stage-salient genes were benchmarked using normals-augmented dataset, and cross-referenced with existing knowledge. The candidate biomarkers were used to construct the feature space for learning an optimal model for the digital screening of early-stage colorectal cancers. The candidate biomarkers were also examined for constructing a prognostic model based on survival analysis.

Results

Among the biomarkers identified are: CRLF1, CALB2, STAC2, UCHL1, KCNG1 (stage-I salient), KLHL34, LPHN3, GREM2, ADCY5, PLAC2, DMRT3 (stage-II salient), PIGR, HABP2, SLC26A9 (stage-III salient), GABRD, DKK1, DLX3, CST6, HOTAIR (stage-IV salient), and CDH3, KRT80, AADACL2, OTOP2, FAM135B, HSP90AB1 (top linear model genes). In particular the study yielded 31 genes that are progression-significant such as ESM1, DKK1, SPDYC, IGFBP1, BIRC7, NKD1, CXCL13, VGLL1, PLAC1, SPERT, UPK2, and interestingly three members of the LY6G6 family. Significant monotonic linear model genes included HIGD1A, ACADS, PEX26, and SPIB. A feature space of just seven biomarkers, namely ESM1, DHRS7C, OTOP3, AADACL2, LPHN3, GABRD, and LPAR1, was sufficient to optimize a RandomForest model that achieved > 98% balanced accuracy (and performant recall) of cancer vs. normal on external validation. Design of an optimal multivariate model based on survival analysis yielded a prognostic panel of three stage-IV salient genes, namely HOTAIR, GABRD, and DKK1. Based on the above sparse signatures, we have developed COADREADx, a web-server for potentially assisting colorectal cancer screening and patient risk stratification. COADREADx provides uncertainty measures for its predictions and needs clinical validation. It has been deployed for experimental non-commercial use at: https://apalanialab.shinyapps.io/coadreadx/.
Exploring tumor endothelial cells heterogeneity in hepatocellular carcinoma: insights from single-cell sequencing and pseudotime analysis
Authors: Sun Jiachun , Zhang Shujun , Liu Yafeng , Liu Kaijie , Gu Xinyu
Published: October 2024

Objective

This study aimed to explore the heterogeneity of tumor endothelial cells (TECs) in hepatocellular carcinoma (HCC) and their role in tumor progression, with the goal of identifying new therapeutic targets and strategies to improve patient prognosis.

Methods

Single-cell RNA sequencing data from nine primary liver cancer samples were analyzed, obtained from the Gene Expression Omnibus (GEO) database. Data preprocessing, normalization, dimensionality reduction, and batch effect correction were performed based on the Seurat package. HCC cell types were identified using uniform manifold approximation and projection (UMAP) and cluster analysis, and the different cell types were annotated using the CellMarker database. Pseudotime trajectory analysis was conducted with Monocle to explore the differentiation trajectory of TECs. MAPK signaling pathway activity and copy number variations (CNV) in TECs were analyzed in conjunction with data from The Cancer Genome Atlas (TCGA), the trans-well and wound healing assay was used for cell invasion and migration activity assessment.

Results

Two subgroups of TECs (TECs 1 and TECs 2) were identified, exhibiting distinct functional activities and signaling pathways. Specifically, TECs 1 may be involved in tumor cell proliferation and inflammatory responses, whereas TECs 2 is not only involved in cell proliferation pathways, but also enriched in pathways such as metabolic synthesis. Pseudotime analysis revealed dynamic changes in TECs subgroups during HCC progression, correlating specific gene expressions (such as PDGFRB, PGF, JUN, and NR4A1). Subsequently, the JUN gene was predicted by performing binding sites and was shown to act as a transcription factor that may regulate the expression of the PGF gene. CNV analysis highlighted key genes and pathways in TECs that might influence HCC progression, and the PGF as key regulatory factor mediated cell proliferation and migration.

Conclusion

The study revealed the heterogeneity of TECs in HCC and their potential roles in tumor progression, offering new perspectives and potential therapeutic targets for HCC molecular mechanisms. The findings emphasize the importance of further exploring TECs heterogeneity for understanding HCC pathogenesis and developing personalized treatment strategies.
The impact of maternal serum biomarkers on maternal and neonatal outcomes in twin pregnancies: a retrospective cohort study conducted at a tertiary hospital
Authors: Wu Hanglin , Yu Liming , Xie Zhen , Cai Hongxia , Wen Caihe
Published: October 2024

Background

Prior prediction models used for screening preeclampsia (PE) in twin pregnancies were found to be inadequate. In singleton pregnancies, various maternal biomarkers have been shown to be correlated with negative pregnancy outcomes. However, the impact of these biomarkers in twin pregnancies remained uncertain.

Methods

A retrospective cohort study was carried out on 736 twin pregnancies at a tertiary hospital in Hangzhou, China. Multivariable logistic models were employed to examine the association between levels of serological markers and the likelihood of adverse pregnancy outcomes. The final logistic model was formulated as a user-friendly nomogram. The primary outcome assessed was the occurrence of PE. Results were presented as odds ratios (ORs) with corresponding 95% confidence intervals (CIs).

Results

The prevalence of PE in the study was 10.3%. When comparing women diagnosed with PE to those without, it was evident that the former group experienced a significantly higher risk of unfavorable maternal and neonatal outcomes. A multivariable logistic regression analysis revealed notable associations between various factors including maternal age, parity, gestational weight gain, a family history of hypertension, as well as levels of cholesterol, albumin, and creatinine and the risk of developing PE, with a significance level of P < 0.05. The concordance index for the constructed nomogram was determined to be 0.792 (95% CI: [0.739–0.844]). Furthermore, an increment of 1 * 1012/L in red blood cell (RBC) count was associated with more than a two-fold increase in the odds of experiencing adverse maternal outcomes (OR 2.247, 95% CI: [1.229–4.107]). However, no significant correlations were identified between any of the examined variables and neonatal outcomes.

Conclusions

In this study, we developed a user-friendly predictive model that achieves notable detection rates by incorporating maternal serum biomarker levels alongside maternal characteristics and medical history. Our findings indicate that the probability of adverse maternal outcomes increases with elevated levels of RBCs. Obstetricians should consider intensifying surveillance for these women in clinical practice.
Fluconazole worsened lung inflammation, partly through lung microbiome dysbiosis in mice with ovalbumin-induced asthma
Authors: Worasilchai Jesadakorn , Thongchaichayakon Piyapat , Chansri Kittipat , Leelahavanichkul Supichaya , Chiewvit Vathin , Visitchanakun Peerapat , Somparn Poorichaya , Hiengrach Pratsanee
Published: October 2024

Innate immunity in asthma may be influenced by alterations in lung microbiota, potentially affecting disease severity. This study investigates the differences in lung inflammation and microbiome between asthma-ovalbumin (OVA) administered with and without fluconazole treatment in C57BL/6 mice. Additionally, the role of inflammation was examined in an in vitro study using a pulmonary cell line. At 30 days post-OVA administration, allergic asthma mice exhibited increased levels of IgE and IL-4 in serum and lung tissue, higher pathological scores, and elevated eosinophils in bronchoalveolar lavage fluid (BALF) compared to control mice. Asthma inflammation was characterized by elevated serum IL-6, increased lung cytokines (TNF-α, IL-6, IL-10), and higher fungal abundance confirmed by polymerase chain reaction (PCR). Fluconazole-treated asthma mice displayed higher levels of cytokines in serum and lung tissue (TNF-α and IL-6), increased pathological scores, and a higher number of mononuclear cells in BALF, with undetectable fungal levels compared to untreated mice. Lung microbiome analysis revealed similarities between control and asthma mice; however, fluconazole-treated asthma mice exhibited higher Bacteroidota levels, lower Firmicutes, and reduced bacterial abundance. Pro-inflammatory cytokine production was increased in supernatants of the pulmonary cell line (NCI-H292) after co-stimulation with LPS and beta-glucan (BG) compared to LPS alone. Fluconazole treatment in OVA-induced asthma mice exacerbated inflammation, partially due to fungi and Gram-negative bacteria, as demonstrated by LPS+BG-activated pulmonary cells. Therefore, fluconazole should be reserved for treating fungal asthma rather than asthma caused by other etiologies.
Co-composting: A Comprehensive Review of Its Potential in Transforming Coir Pith Waste into Nutrient-rich Manure
Authors: Satheesh Ameya , Raj Sheeja K , D Jacob , P Shalini Pillai , K.N Anith
Published: October 2024

Coir industries in India generates around 7.5Mt of coir waste yearly, which is unsuitable for agricultural use due to its high C:N ratio, lignin, phenol, cellulose and tannin content. The accumulation of coir pith leads to adverse environmental problems due to the release of phenolic compounds, lignin, tannins etc. Biodegradation or composting is the best way to manage coir waste and thereby the environmental pollution can be avoided. Co-composting is a method of decomposing multiple organic materials, which aims to create stable humus, and overcome the limitations of composting with a single organic source. Co-composting of coir pith reduces the C:N ratio, lignin content, cellulose content and increases the nutrient contents. In co-composting technology more than one feed stock are used for composting. It can be done by treating the coir pith with organic source of nutrients viz., farm yard manure or poultry manure or agro-industrial wastes or green manure crops or leguminous weeds or treating the coir pith with organic wastes and earthworms, or treating the coir pith lignin degrading micro-organisms and or supplementing the coir pith with lime, rock phosphate etc. along with the organic sources of nutrients mentioned above to speed up the composting process. Co-composting of coir pith resulted in the production of nutrient rich organic manure within a short period of time. Application of coir pith compost had significant effect on the growth and yield attributes of crops. Harnessing the potential of coir pith can lead us towards a more sustainable and greener future.
Al-based Techniques for Comprehensive Crop Nutrition Assessment: A Review
Authors: Parihar Preeti , Tiwary Simran , Behuria Pooja Ranee , Sood Yachna
Published: October 2024

Artificial Intelligence (AI) methodologies, such as machine learning, deep learning, and data fusion, are transforming agricultural practices by offering advanced tools for data-driven decision-making, predictive modeling, and automated processes. This paper explores the latest AI techniques utilized in agriculture to enhance productivity, optimize resource management, and address the challenges posed by climate change. By harnessing AI-driven solutions for crop management, soil analysis, and pest control, these methods significantly contribute to sustainable agriculture, benefiting both farmers and the environment through more efficient and eco-friendly practices. However, while AI holds immense promise, challenges remain in terms of accessibility, data quality, and the adaptation of these techniques to diverse agricultural conditions. This review aims to provide a balanced overview of the current state of AI applications in agriculture, offering insights into the opportunities and limitations faced by this growing field.
Survey on Incidence of Gummy Stem Blight on Watermelon (Citrullus lanatus) in Karnataka, India
Authors: Hanamasagar Yamuna , C. G. Sangeetha, , Belagalla Ninagaraj , Srinivasareddy Hemanth , D. S. Ambika , Sood. Meenakshi , Manchali Shivapriya , Appanna Vikram
Published: October 2024

Watermelon (Citrullus lanatus) is an important cucurbitaceous crop cultivated worldwide. The cultivation of watermelon and other species of the family Cucurbitaceae is severely affected by several diseases like anthracnose, Alternaria leaf spot, bacterial fruit blotch, powdery mildew and gummy stem blight. Among the diseases, gummy stem blight is an emerging and devastating disease caused by Didymella bryoniae producing a serious threat to the economics of production of cucurbits like watermelon. A roving survey was carried out in eight districts of Karnataka (Chamarajanagara, Chikkaballapura, Gulburga, Vijayapur, Bengaluru urban, Kolar, Mysuru and Yadgiri) from 2021 to 2023 to record the incidence of gummy stem blight (GSB) disease on watermelon. The survey data revealed that GSB disease was observed in all areas. The per cent disease index ranged from 29.6 to 51.2 per cent. The maximum mean per cent disease index of (51.2%),) Bengaluru urban district and the lowest was seen in the Mysuru district (29.6%) followed by Chikkaballapura district (31.0%). The pathogen associated with gummy stem blight disease was isolated and proved the pathogenicity of the isolate and fulfilled the Koch’s postulates.
Therapeutic Efficacy of Eucalyptus Oil as Teat Dip in Subclinical Mastitis in Goats
Authors: Singh Mrinal , Tiwari Amita , Gupta Devendra Kumar , Patel Manoj , Nayak Anju , Pradhan Shashi , Singh Brejesh , Pratap Aditya
Published: October 2024

Mastitis, an inflammation of the parenchyma of mammary gland, results in alterations to the chemical and physical composition of milk due to a variety of infectious and non-infectious causes. The present work was conducted in the Department of Veterinary Medicine, College of Veterinary Science and Animal Husbandry, Nanaji Deshmukh Veterinary Science University, Jabalpur, Madhya Pradesh (M.P.). A total of 256 lactating goats irrespective of age, breed, parity and stage of lactation belonging to both organized and unorganized sectors at Jabalpur were screened from “February 2024 to July 2024”. On the basis of modified California mastitis test (MCMT) score, out of 256 lactating goats, 98 goats were found positive for subclinical mastitis with overall occurrence as 38.28% on animal basis and 33.33% on udder halves basis. Therapeutic study on 24 milk samples positive for subclinical mastitis by MCMT was conducted and categorized into four treatment groups (G1, G2, G3 and G4), each group comprised of 6 goats. Six apparently healthy goats were selected as healthy control group (G5). Two different teat dips viz. Eucalyptus oil 98% + DMSO 2% BID for 14 days in groups G1 and G3 and 5% Povidone iodine BID for 14 days in groups G2 and G4 were used as teat dips, respectively. Moreover, goats of groups G3 and G4 were commonly treated with parenteral antibiotic amoxicillin sulbactam @10 mg/kg b.wt. I/M OD for 3 days. Significantly higher values of somatic cell count, standard plate count, pH, freezing point and significantly lower value of lactose were observed in subclinical mastitis affected goats. The mean density and mean water percentage values varied within normal physiological range. On the basis of restoration of milk parameters and standard plate count, the most effective therapy was elicited by Eucalyptus oil 98%+ DMSO 2% as teat dip in combination with antibiotic amoxicillin sulbactam (G3).
Genetic Variability Studies in F2 Populations of Ridge Gourd [Luffa acutangula L. (Roxb.)] for Growth, Yield and Quality Traits
Authors: Kavya  , Hadimani H. P. , Evoor Shashikanth , D Satish , Venkateshalu
Published: October 2024

An experiment was conducted to study, genetic variability in ridge gourd during rabi 2024 at College of Horticulture, Bagalkot. The observations were recorded on various growth, yield and quality contributing characters of population-I (ArkaPrasan x Sirsi Local-2) and population-II (Jaipur Long x KLR-5). The analysis of variance indicated the prevalence of sufficient genetic variation among the genotypes from all the characters studied. The high phenotypic coefficient of variation (PCV) and genotypic coefficient of variation (GCV) were observed for node at first male flower appears, node at first female appears, TSS and crude fibre in population-I. Whereas, the traits like vine length, number of primary branches per vine, average fruit weight, fruit yield per vine and crude fibre in population-II. High heritability coupled with high genetic advance were observed for node at first male flower appears, node at first female flower appears, fruit length, fruit diameter, average fruit weight, fruit yield per vine, number of fruits per vine, number of seeds per fruit, fruit tenderness, TSS, crude fibre and vitamin C in the both F2 populations indicating these characters are governed by additive gene action. Hence, direct selection may be followed for the improvement of ridge gourd for these characters.
Der Richter und sein Lenker
Authors: Schirrmeister Véronique
Published: October 2024

Der Beitrag befasst sich mit den normativen Evaluationskriterien für richterliches Entscheiden, die sich aus den Rechtskonzeptionen von Dworkin und Hart ableiten lassen. Aus diesen werden Rückschlüsse auf die Legitimität strategischer Prozessführung gezogen. Aus Harts Perspektive können transformatorische Gerichtsentscheidungen nicht als Teil der Rechtsanwendung angesehen werden. Bei Dworkin hingegen sind sie legitim, wenn sie die bestmögliche Interpretation der Rechtspraxis als Ganzes darstellen. Eine Beurteilung strategischer Prozessführungspraktiken setzt deshalb ein Bekenntnis zu einem Rechtsentwurf voraus.
Fragmented Canopies Control the Regimes of Gravity Current Development
Authors: Barcelona Aina , Serra Teresa , Colomer Jordi
Published: February 2018

Coastal ecosystems (marine littoral regions, wetlands, and deltas) are regions of high biological productivity. However, they are also one of the world's most threatened ecosystems. Wetlands are characterized by aquatic vegetation adapted to high salinity levels and climatic variations. Wetland canopies buffer these hydrodynamic and atmospheric variations and help retain sediment by reducing current velocity during sea storms or runoff after periods of rain. This work focuses on the effect of the presence of a gap (i.e., nonvegetated zone) parallel to the direction of the main current has on the sedimentation and hydrodynamics of a gravity current. The study aims to (1) address the behavior of a gravity current in a vegetated region compared to one without vegetation (i.e., the gap), (2) determine the effect gap size has on how a gravity current evolves, and 3) determine the effect gap sizes have on the sedimentary rates from a gravity current. Laboratory experiments were carried out in a flume using four different sediment concentrations, four different canopy densities (884, 354, 177, and 0 plants·m−2) and three different gap widths (H/2, H, and 1.5H, where H is the height of the water). This work shows that a gravity current's evolution and its sedimentary rates depend on the fractional volume occupied by the vegetation. While current dynamics in experiments with wider gaps are similar to the nonvegetated case, for smaller gaps the dynamics are closer to the fully vegetated case. Nonetheless, the gravity current exhibits the same behavior in both the vegetated region and the gap.
Bio‐Optical Data Assimilation With Observational Error Covariance Derived From an Ensemble of Satellite Images
Authors: Shulman Igor , Gould Richard W. , Frolov Sergey , McCarthy Sean , Penta Brad , Anderson Stephanie , Sakalaukus Peter
Published: February 2018

An ensemble‐based approach to specify observational error covariance in the data assimilation of satellite bio‐optical properties is proposed. The observational error covariance is derived from statistical properties of the generated ensemble of satellite MODIS‐Aqua chlorophyll (Chl) images. The proposed observational error covariance is used in the Optimal Interpolation scheme for the assimilation of MODIS‐Aqua Chl observations. The forecast error covariance is specified in the subspace of the multivariate (bio‐optical, physical) empirical orthogonal functions (EOFs) estimated from a month‐long model run. The assimilation of surface MODIS‐Aqua Chl improved surface and subsurface model Chl predictions. Comparisons with surface and subsurface water samples demonstrate that data assimilation run with the proposed observational error covariance has higher RMSE than the data assimilation run with “optimistic” assumption about observational errors (10% of the ensemble mean), but has smaller or comparable RMSE than data assimilation run with an assumption that observational errors equal to 35% of the ensemble mean (the target error for satellite data product for chlorophyll). Also, with the assimilation of the MODIS‐Aqua Chl data, the RMSE between observed and model‐predicted fractions of diatoms to the total phytoplankton is reduced by a factor of two in comparison to the nonassimilative run.
Three‐Dimensional Ageostrophic Motion and Water Mass Subduction in the Southern Ocean
Authors: Buongiorno Nardelli B. , Mulet S. , Iudicone D.
Published: February 2018

Vertical velocities at the ocean mesoscale are several orders of magnitude smaller than corresponding horizontal flows, making their direct monitoring a still unsolved challenge. Vertical motion is generally retrieved indirectly by applying diagnostic equations to observation‐based fields. The most common approach relies on the solution of an adiabatic version of the Omega equation, neglecting the ageostrophic secondary circulation driven by frictional effects and turbulent mixing in the boundary layers. Here we apply a diabatic semigeostrophic diagnostic model to two different 3‐D reconstructions covering the Southern Ocean during the period 2010–2012. We incorporate the effect of vertical mixing through a modified K‐profile parameterization and using ERA‐interim data, and perform an indirect validation of the ageostrophic circulation with independent drifter observations. Even if horizontal gradients and associated vertical flow are likely underestimated at 1/4° × 1/4° resolution, the exercise provides an unprecedented relative quantification of the contribution of vertical mixing and adiabatic internal dynamics on the vertical exchanges along the Antarctic Circumpolar Current. Kinematic estimates of subduction rates show the destruction of poleward flowing waters lighter than 26.6 kg/m3 (14 ÷ 15 Sv) and two main positive bands associated with the Antarctic Intermediate Water (7 ÷ 11 Sv) and Sub‐Antarctic Mode Waters (4 ÷ 7 Sv) formation, while Circumpolar Deep Water upwelling attains around 3 ÷ 6 Sv. Diabatic and adiabatic terms force distinct spatial responses and vertical velocity magnitudes along the water column and the restratifying effect of adiabatic internal dynamics due to mesoscale eddies is shown to at least partly compensate the contribution of wind‐driven vertical exchanges to net subduction.
Seismic Characterization of Oceanic Water Masses, Water Mass Boundaries, and Mesoscale Eddies SE of New Zealand
Authors: Gorman Andrew R. , Smillie Matthew W. , Cooper Joanna K. , Bowman M. Hamish , Vennell Ross , Holbrook W. Steven , Frew Russell
Published: February 2018

The Subtropical and Subantarctic Fronts, which separate Subtropical, Subantarctic, and Antarctic Intermediate Waters, are diverted to the south of New Zealand by the submerged continental landmass of Zealandia. In the upper ocean of this region, large volumes of dissolved or suspended material are intermittently transported across the Subtropical Front; however, the mechanisms of such transport processes are enigmatic. Understanding these oceanic boundaries in three dimensions generally depends on measurements collected from stationary vessels and moorings. The details of these data sets, which are critical for understanding how water masses interact and mix at the fine‐scale (<10 m) to mesoscale (10–100 km), are inadequately constrained due to resolution considerations. Southeast of New Zealand, high‐resolution seismic reflection images of oceanic water masses have been produced using petroleum industry data. These seismic sections clearly show three main water masses, the boundary zones (fronts) between them, and associated thermohaline fine structure that may be related to the mixing of water masses in this region. Interpretations of the data suggest that the Subtropical Front in this region is a landward‐dipping zone, with a width that can vary between 20 and 40 km. The boundary zone between Subantarctic Waters and the underlying Antarctic Intermediate Waters is also observed to dip landward. Several isolated lenses have been identified on the three data sets, ranging in size from 9 to 30 km in diameter. These lenses are interpreted to be mesoscale eddies that form at relatively shallow depths along the south side of the Subtropical Front.
International consensus statement on allergy and rhinology: allergic rhinitis—executive summary
Authors: Wise Sarah K. , Lin Sandra Y. , Toskala Elina
Published: February 2018

Background

The available allergic rhinitis (AR) literature continues to grow. Critical evaluation and understanding of this literature is important to appropriately utilize this knowledge in the care of AR patients. The International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR) has been produced as a multidisciplinary international effort. This Executive Summary highlights and summarizes the findings of the comprehensive ICAR:AR document.

Methods

The ICAR:AR document was produced using previously described methodology. Specific topics were developed relating to AR. Each topic was assigned a literature review, evidence‐based review (EBR), or evidence‐based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus.

Results

Over 100 individual topics related to AR diagnosis, pathophysiology, epidemiology, disease burden, risk factors, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR were addressed in the comprehensive ICAR:AR document. Herein, the Executive Summary provides a synopsis of these findings.

Conclusion

In the ICAR:AR critical review of the literature, several strengths were identified. In addition, significant knowledge gaps exist in the AR literature where current practice is not based on the best quality evidence; these should be seen as opportunities for additional research. The ICAR:AR document evaluates the strengths and weaknesses of the AR literature. This Executive Summary condenses these findings into a short summary. The reader is also encouraged to consult the comprehensive ICAR:AR document for a thorough description of this work.
International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis
Authors: Wise Sarah K. , Lin Sandra Y. , Toskala Elina , Orlandi Richard R. , Akdis Cezmi A. , Alt Jeremiah A. , Azar Antoine , Baroody Fuad M. , Bachert Claus , Canonica G. Walter , Chacko Thomas , Cingi Cemal , Ciprandi Giorgio , Corey Jacquelynne , Cox Linda S. , Creticos Peter Socrates , Custovic Adnan , Damask Cecelia , DeConde Adam , DelGaudio John M. , Ebert Charles S. , Eloy Jean Anderson , Flanagan Carrie E. , Fokkens Wytske J. , Franzese Christine , Gosepath Jan , Halderman Ashleigh , Hamilton Robert G. , Hoffman Hans Jürgen , Hohlfeld Jens M. , Houser Steven M. , Hwang Peter H. , Incorvaia Cristoforo , Jarvis Deborah , Khalid Ayesha N. , Kilpeläinen Maritta , Kingdom Todd. T. , Krouse Helene , Larenas‐Linnemann Desiree , Laury Adrienne M. , Lee Stella E. , Levy Joshua M. , Luong Amber U. , Marple Bradley F. , McCoul Edward D. , McMains K. Christopher , Melén Erik , Mims James W. , Moscato Gianna , Mullol Joaquim , Nelson Harold S. , Patadia Monica , Pawankar Ruby , Pfaar Oliver , Platt Michael P. , Reisacher William , Rondón Carmen , Rudmik Luke , Ryan Matthew , Sastre Joaquin , Schlosser Rodney J. , Settipane Russell A. , Sharma Hemant P. , Sheikh Aziz , Smith Timothy L. , Tantilipikorn Pongsakorn , Tversky Jody R. , Veling Maria C. , Wang De Yun , Westman Marit , Wickman Magnus , Zacharek Mark
Published: February 2018

Background

Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).

Methods

Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence‐based review (EBR), or evidence‐based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus.

Results

The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR.

Conclusion

This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.
An Efficient Aerobic Oxidation Protocol of Aldehydes to Carboxylic Acids in Water Catalyzed by an Inorganic‐Ligand‐Supported Copper Catalyst
Authors: Yu Han , Ru Shi , Zhai Yongyan , Dai Guoyong , Han Sheng , Wei Yongge
Published: February 2018

A method for the aerobic oxidation of aldehydes to carboxylic acids in water by using an inorganic‐ligand‐supported copper catalyst was developed. This method was performed with the use of atmospheric oxygen as the sole oxidant under extremely mild aqueous conditions, and furthermore, a wide range of aldehydes with various functional groups were tolerated. The copper catalyst could be recycled and used in successive reactions at least six times without any appreciable degradation in performance. This method is operationally simple and avoids the use of high‐costing, toxic, air/moisture‐sensitive, and commercially unavailable organic ligands. The generality of this method gives it potential to be used on the industrial scale.
Restoration of eastern oyster populations with positive density dependence
Authors: Moore Jacob L. , Puckett Brandon J. , Schreiber Sebastian J.
Published: February 2018

Positive density dependence (i.e., Allee effects) can create a threshold of population states below which extinction of the population occurs. The existence of this threshold, which can often be a complex, multi‐dimensional surface, rather than a single point, is of particular importance in degraded populations for which there is a desire for successful restoration. Here, we incorporated positive density dependence into a closed, size‐ and age‐structured integral projection model parameterized with empirical data from an eastern oyster, Crassostrea virginica, population in Pamlico Sound, North Carolina, USA. To understand the properties of the threshold surface, and implications for restoration, we introduced a general method based on a linearization of the threshold surface at its unique, unstable equilibrium. We estimated the number of oysters of a particular age (i.e., stock enhancement), or the surface area of dead shell substrate required (i.e., habitat enhancement) to move a population from an extinction trajectory to a persistence trajectory. The location of the threshold surface was strongly affected by changes in the amount of local larval retention. Traditional stock enhancement with oysters <1 yr old (i.e., spat) required three times as many oysters relative to stock enhancement with oysters between ages 3 and 7 yr old, while the success of habitat enhancement depended upon the initial size distribution of the population. The methodology described here demonstrates the importance of considering positive density dependence in oyster populations, and also provides insights into effective management and restoration strategies when dealing with a high dimensional threshold separating extinction and persistence.
Individual heterogeneity and early life conditions shape growth in a freshwater top predator
Authors: Nater Chloé R. , Rustadbakken Atle , Ergon Torbjørn , Langangen Øystein , Moe S. Jannicke , Vindenes Yngvild , Vøllestad Leif Asbjørn , Aass Per
Published: February 2018

Body size can have profound impacts on survival, movement, and reproductive schedules shaping individual fitness, making growth a central process in ecological and evolutionary dynamics. Realized growth is the result of a complex interplay between life history schedules, individual variation, and environmental influences. Integrating all of these aspects into growth models is methodologically difficult, depends on the availability of repeated measurements of identifiable individuals, and consequently represents a major challenge in particular for natural populations. Using a unique 30‐yr time series of individual length measurements inferred from scale year rings of wild brown trout, we develop a Bayesian hierarchical model to estimate individual growth trajectories in temporally and spatially varying environments. We reveal a gradual decrease in average juvenile growth, which has carried over to adult life and contributed to decreasing sizes observed at the population level. Commonly studied environmental drivers like temperature and water flow did not explain much of this trend and overall persistent and among‐year individual variation dwarfed temporal variation in growth patterns. Our model and results are relevant to a wide range of questions in ecology and evolution requiring a detailed understanding of growth patterns, including conservation and management of many size‐structured populations.
Cumulative effects of multiple pain sites in youth with chronic pain
Authors: Basch M.C. , Chow E.T. , Logan D.E. , Borsook D. , Schechter N.L. , Simons L.E.
Published: February 2018

Background

The experience of persistent pain in multiple locations is common in youth. Based on current literature, youth with multiple pain sites (MPS) are at risk of experiencing poorer emotional outcomes and a spread of symptoms into late adolescence and adulthood. Little is known regarding the association between MPS with physical and school functioning domains, particularly after initiation of multidisciplinary pain treatment. Therefore, the objective of this study was to examine the association of MPS with disability and school functioning among youth with chronic pain.

Methods

A total of 195 patients with chronic pain, aged 8–17, and their parents completed measures assessing patient distress and functioning at a multidisciplinary pain clinic evaluation and at 4‐month follow‐up.

Results

At evaluation, 63% of patients presented with MPS; 25% reporting MPS endorsed pain in five or more locations. When controlling for relevant demographic and emotional distress factors, MPS were associated with lower school functioning at evaluation with a persistent trend at follow‐up. Although MPS were not a significant predictor of pain‐related disability at evaluation, it emerged as significant at follow‐up.

Conclusions

Potentially due to the MPS load and the inverse effects that such a pain state has on function, such patients may be at risk for poorer health and school‐related outcomes. The mechanisms influencing these relationships appear to extend beyond psychological/emotional factors and warrant further investigation in order to aid in our understanding of youth with MPS.

Significance

Youth with MPS may be at risk for experiencing poorer physical and school functioning in comparison with single‐site peers, despite treatment initiation. Further research is warranted to inform assessment and treatment approaches for this subgroup of patients.
Tumor necrosis factor‐α‐mediated hepatocyte apoptosis stimulates fibrosis in the steatotic liver in mice
Authors: Osawa Yosuke , Kojika Ekumi , Hayashi Yukiko , Kimura Masamichi , Nishikawa Koji , Yoshio Sachiyo , Doi Hiroyoshi , Kanto Tatsuya , Kimura Kiminori
Published: February 2018

Hepatocyte apoptosis has been implicated in the progression of nonalcoholic steatohepatitis. However, it is unclear whether the induction of tumor necrosis factor (TNF)‐α‐mediated hepatocyte apoptosis in the simple fatty liver triggers liver fibrosis. To address this question, high‐fat diet‐fed mice were repeatedly administered D‐galactosamine, which increases the sensitivity of hepatocytes to TNF‐α‐mediated apoptosis. In mice treated with a high‐fat diet plus D‐galactosamine, hepatocyte apoptosis and liver fibrosis were induced, whereas both apoptosis and fibrosis were inhibited in these mice following gut sterilization with antimicrobials or knockout of TNF‐α. Furthermore, liver fibrosis was diminished when hepatocyte apoptosis was inhibited by expressing a constitutively active inhibitor of nuclear factor κB kinase subunit β. Thus, hepatocyte apoptosis induced by intestinal dysbiosis or TNF‐α up‐regulation in the steatotic liver caused fibrosis. Organ fibrosis, including liver fibrosis, involves the interaction of cyclic adenosine monophosphate‐response element‐binding protein‐binding protein (CBP) and β‐catenin. Here, hepatocyte‐specific CBP‐knockout mice showed reduced liver fibrosis accompanied by hepatocyte apoptosis diminution; notably, liver fibrosis was also decreased in mice in which CBP was specifically knocked out in collagen‐producing cells because the activation of these cells was now suppressed. Conclusion: TNF‐α‐mediated hepatocyte apoptosis induced fibrosis in the steatotic liver, and inhibition of CBP/β‐catenin signaling attenuated the liver fibrosis due to the reduction of hepatocyte apoptosis and suppression of the activation of collagen‐producing cells. Thus, targeting CBP/β‐catenin may represent a new therapeutic strategy for treating fibrosis in nonalcoholic steatohepatitis. (Hepatology Communications 2018;2:407‐420)
Prioritization of antiretroviral therapy in patients with high CD4 counts, and retention in care: lessons from the START and Temprano trials
Authors: Schechter Mauro
Published: February 2018

Initiation of antiretroviral therapy is not a once in a lifetime opportunity. In some resource constrained settings financial limitations make it necessary to prioritize treatment initiation for some groups of patients. In developed countries, there are patients who are reluctant to initiate treatment. Subgroup analysis of the START trial can inform recommendations for which patients with CD4 counts >500 cells mm3 temporary postponement of treatment initiation is safer. These include individuals aged <30 years and/or with CD4/CD8 ratio of >0.8 and/or viral load of <5000. This is because these individuals are at very low risk of disease progression in the subsequent 2 to 3 years, the risk is minimally diminished by antiretroviral therapy and is virtually identical in the first 18 months of therapy regardless of treatment initiation. In addition, asymptomatic young individuals are at higher risk of loss‐to‐follow and of low adherence to treatment, and those with low viral loads are less likely to transmit the virus. In addition, lessons from START and Temprano can help design trials to investigate strategies to decrease losses‐to‐follow‐up, while minimizing risks to patients.
Novel radiomic signature as a prognostic biomarker for locally advanced rectal cancer
Authors: Meng Yankai , Zhang Yuchen , Dong Di , Li Chunming , Liang Xiao , Zhang Chongda , Wan Lijuan , Zhao Xinming , Xu Kai , Zhou Chunwu , Tian Jie , Zhang Hongmei
Published: February 2018

Background

Locally advanced rectal cancer (LARC) patient stratification by clinicoradiologic factors may yield variable results. Therefore, more efficient prognostic biomarkers are needed for improved risk stratification of LARC patients, personalized treatment, and prognostication.

Purpose/Hypothesis

To compare the ability of a radiomic signature to predict disease‐free survival (DFS) with that of a clinicoradiologic risk model in individual patients with LARC.

Study Type

Retrospective study.

Population

In all, 108 consecutive patients (allocated to a training and validation set with a 1:1 ratio) with LARC treated with neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME).

Field Strength/Sequence

Axial 3D LAVA multienhanced MR sequence at 3T.

Assessment

ITK‐SNAP software was used for manual segmentation of 3D pre‐nCRT MR images. All manual tumor segmentations were performed by a gastrointestinal tract radiologist, and validated by a senior radiologist. The clinicoradiologic risk factors with potential prognostic outcomes were identified in univariate analysis based on the Cox regression model for the whole set. The results showed that ypT, ypN, EMVI, and MRF were potential clinicoradiologic risk factors. Interestingly, only ypN and MRF were identified as independent predictors in multivariate analysis based on the Cox regression model.

Statistical Tests

A radiomic signature based on 485 3D features was generated using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The association of the radiomic signature with DFS was investigated by Kaplan–Meier survival curves. Survival curves were compared by the log‐rank test. Three models were built and assessed for their predictive values, using the Harrell concordance index and integrated time‐dependent area under the curve.

Results

The novel radiomic signature stratified patients into low‐ and high‐risk groups for DFS in the training set (hazard ratio [HR] = 6.83; P < 0.001), and was successfully validated in the validation set (HR = 2.92; P < 0.001). The model combining the radiomic signature and clinicoradiologic findings had the best performance (C index = 0.788, 95% confidence interval [CI] 0.72–0.86; integrated time‐dependent area under the curve of 0.837 at 3 years).

Data Conclusion

The novel radiomic signature could be used to predict DFS in patients with LARC. Furthermore, combining this radiomic signature with clinicoradiologic features significantly improved the ability to estimate DFS (P = 0.001, 0.005 in training set and in validation set, respectively), and may help guide individualized treatment in such patients.

Level of Evidence: 3

Technical Efficacy: Stage 5

J. Magn. Reson. Imaging 2018;48:605–614.
Evaluation of Porcine Meat and Bone Meal in Diets for Pond-Raised Hybrid Catfish
Authors: Li Menghe H , Bosworth Brian G , Lucas Penelope M
Published: February 2018

The present study examined effects of various levels (0, 10, 15, 20, and 25%) of porcine meat and bone meal (PMBM) in diets on production and processing characteristics and body composition of pond-raised hybrid catfish (female Channel Catfish Ictalurus punctatus × male Blue Catfish Ictalurus furcatus). Large fingerlings (mean ± SD initial weight per fish = 58 ± 2.3 g) were stocked into 25 0.04-ha earthen ponds at a stocking rate of 14,826 fish/ha. Fish were fed to apparent satiation once a day for 155 d. There were no significant differences in total feed fed, weight gain, or survival among dietary treatments, but fish fed diets containing 10% or more PMBM had significantly greater net yield and a lower feed conversion ratio than fish fed the control diet without PMBM. No significant differences were detected for carcass yield and fillet yield among dietary treatments by ANOVA, but carcass yield and fillet yield decreased and fillet fat levels increased linearly with increasing PMBM levels. Results from the present study demonstrate that 10% PMBM could be used in the diet for an entire growing season without marked impacts on growth, processing yield, or body composition of pond-raised hybrid catfish. Higher PMBM levels up to 25% may be used for short-term feeding when its price is favorable compared with soybean meal. However, cautions should be taken when using high levels of PMBM during the later part of the growth cycle because of the negative effects on processing yield and fillet fat levels.
Survival of Pellet-Reared, Naturalized, and Wild Advanced-Size Largemouth Bass Exposed to Angling and Handling Stressors
Authors: Keretz Kevin R , Dinken Colin P , Allen Peter J , Schramm Harold L
Published: February 2018

Large numbers of advanced-size Largemouth Bass Micropterus salmoides needed for stocking and studies investigating the effects of environmental and angling stressors may be produced using formulated diets. However, fish reared on formulated diets can have lower survival than wild fish. Although survival can be improved by briefly feeding cultured fish a live fish diet prior to stocking (herein, termed naturalization), the time needed for pellet-reared fish undergoing naturalization to show improved and stable survival (i.e., to become naturalized) compared with pellet-reared fish following a series of sublethal stressors has not been determined. Further, the difference in survival of pellet-reared, naturalized, and wild advanced-size Largemouth Bass following exposure to sublethal stressors has not been evaluated under controlled conditions. We conducted experiments to determine (1) the time required for pellet-reared advanced-size (246–373 mm TL) Largemouth Bass to become naturalized following a series of sublethal stressors and (2) differences in survival of pellet-reared, naturalized, and wild advanced-sized Largemouth Bass subjected to two different series of sublethal stressors. Survival was high and did not significantly differ before (85%) and after 1–12 weeks of naturalization (90–100%). Survival was 100% for pellet-reared, naturalized, and wild Largemouth Bass following the series of sublethal stressors. We found no difference in survival among pellet-reared, naturalized, and wild Largemouth Bass challenged with a series of sublethal stressors.