bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA sequencing identifies lung cancer lineage and facilitates drug repositioning
Authors: Zeng Longjin , Zhang Longyao , Li Lingchen , Liao Xingyun , Yin Chenrui , Zhang Lincheng , Chen Xiewan , Sun Jianguo
Published: September 2024

Recent breakthrough therapies have improved survival rates in non-small cell lung cancer (NSCLC), but a paradigm for prospective confirmation is still lacking. Patientdatasets were mainly downloaded from TCGA, CPTAC and GEO. We conducted downstream analysis by collecting metagenes and generated 42-gene subtype classifiers to elucidate biological pathways. Subsequently, scRNA, eRNA, methylation, mutation, and copy number variation were depicted from a phenotype perspective. Enhancing the clinical translatability of molecular subtypes, preclinical models including CMAP, CCLE, and GDSC were utilized for drug repositioning. Importantly, we verified the presence of previously described three phenotypes including bronchioid, neuroendocrine, and squamoid. Poor prognosis was seen in squamoid and neuroendocrine clusters for treatment-naive and immunotherapy populations. The neuroendocrine cluster was dominated by STK11 mutations and 14q13.3 amplifications, whose related methylated loci are predictive of immunotherapy. And the greatest therapeutic potential lies in the bronchioid cluster. We further estimated the relative cell abundance of the tumor microenvironment (TME), specific cell types could be reflected among three clusters. Meanwhile, the higher portion of immune cell infiltration belonged to bronchioid and squamoid, not the neuroendocrine cluster. In drug repositioning, MEK inhibitors resisted bronchioid but were squamoid-sensitive. To conceptually validate compounds/targets, we employed RNA-seq and CCK-8/western blot assays. Our results indicated that dinaciclib and alvocidib exhibited similar activity and sensitivity in the neuroendocrine cluster. Also, a lineage factor named KLF5 recognized by inferred transcriptional factors activity could be suppressed by verteporfin.
Spurious Regressions in Agricultural Commodities Price Modeling: Autocorrelation and Time Trend Misspecification.
Authors:   ,   Pontificia Universidad Católica de Chile. Facultad de Agronomía y Sistemas Naturales, Fuica Barrios Andrés
Published: September 2024

Este estudio replica y analiza el trabajo de Roberts & Schlenker sobre los efectos del mandato de etanol en los precios de granos agrícolas, enfocándose en análisis de robustez. Se evaluaron diferentes tendencias temporales, se abordó la autocorrelación de residuos y se examinó la fortaleza de los instrumentos. Los hallazgos revelan que la elección de la tendencia temporal impacta significativamente los resultados, sugiriendo una posible especificación errónea del modelo. La presencia de autocorrelación de primer orden en los residuos genera preocupaciones sobre la robustez de los hallazgos originales. Se empleó la transformación de Cochrane-Orcutt para refinar las estimaciones econométricas, demostrando elasticidades de oferta y demanda consistentes entre diferentes tendencias temporales después de la transformación. Adicionalmente, las pruebas de instrumentos débiles indican susceptibilidad a la distorsión de tamaño en los coeficientes estimados. Este estudio enfatiza la importancia de abordar las tendencias temporales seculares y la autocorrelación en el modelado de precios de commodities para garantizar la confiabilidad y validez de las inferencias econométricas. Los hallazgos contribuyen al avance de la investigación empírica en economía agrícola y proporcionan una base para evaluaciones más precisas del impacto de políticas en estudios posteriores.Palabras clave: Modelación de precios de commodities; Análisis econométrico; Corrección de autocorrelación; Efectos del mandato de etanol; Análisis de tendencias temporales; Regresión con variables instrumentales; Elasticidades de oferta y demanda.
Desarrollo de Habilidades Transversales en estudiantes de pregrado de Terapia Ocupacional, Kinesiología y Fonoaudiología a través del Aprendizaje Servicio: un Scoping Review
Authors:   , Estrada Palavecino Leonardo Andrés
Published: September 2024

La Educación Médica Basada en Evidencia orienta las elecciones metodológicas asegurando efectividad en los procesos formativos. Existe evidencia del desarrollo de habilidades transversales en estudiantes de pregrado de terapia ocupacional, kinesiología y fonoaudiología a través del Aprendizaje Servicio, pero no está debidamente sistematizada, por lo que no se conoce con claridad cuáles son las habilidades transversales mayormente desarrolladas a través de este enfoque metodológico. Se vuelve necesario explorar cuál es el nivel de desarrollo de habilidades transversales a través del Aprendizaje Servicio en estudiantes de pregrado de estas carreras, justificando su elección metodológica. Método: Se realiza un Scoping Review de la literatura relacionada en 4 bases de datos (PubMED, ERIC, Liliacs y Web of Science), aplicando la escala SANRA de evaluación de análisis narrativos y el protocolo CASP para el análisis temático. Resultados: de 248 artículos encontrados en 4 bases de datos, 23 artículos cumplieron con criterios de inclusión; más del 50% de los seleccionados presentó criterios de alta calidad. Se identificaron seis habilidades de alto desarrollo en la estrategia de Aprendizaje y Servicio: trabajo en equipo, identificación del rol profesional, habilidades interculturales, autoeficacia, pensamiento crítico y competencias globales. Conclusiones: La metodología de Aprendizaje Servicio, aplicada bajo ciertas condiciones, facilita el desarrollo de habilidades transversales en estudiantes de pregrado de terapia ocupacional, kinesiología y fonoaudiología, además de otras competencias necesarias para el desempeño profesional. Se proyecta la necesidad de desarrollar protocolos de implementación de la metodología para asegurar su efectividad.
Experiencias de aprendizaje de la Lengua de Señas Chilena desde la perspectiva de padres oyentes con hijos/as Sordos: factores facilitadores, motivadores y obstaculizadores de su acercamiento a la Lengua de Señas Chilena
Authors:   , Sánchez Herrera Catalina
Published: September 2024

Antecedentes: El acceso temprano a la lengua de señas se considera fundamental para el desarrollo de los niños/as Sordos. Sin embargo, alrededor del 90% de ellos nacen en familias de oyentes que no han tenido contacto previo con esta lengua y se estima que solo un 20%de esas familias utiliza la lengua de señas de forma regular en la comunicación con su hijo/a. Objetivo: Conocer la perspectiva de padres y madres con hijos/as Sordos sobre su relación con el aprendizaje de la Lengua de Señas (LS).Participantes y Método: Se realizó un estudio descriptivo, analítico, relacional y exploratorio con enfoque cualitativo. Se entrevistó a 13 padres y madres de dos colegiospara Sordos en Santiago, Chile. El análisis se basó en la Teoría Fundamentada, utilizandola estrategia de codificación abierta y axial. Resultados: Los datos se agruparon en cuatro categorías principales, revelando las experiencias de los padres y madres respecto al diagnóstico de sordera y la adquisición de la lengua de señas. Esto permitió realizar un análisis de trayectorias relacionadas con la lengua de señas. Conclusiones: El diagnóstico se describe como un momento de shock emocional, con unenfoque médico hacia la sordera que limita el acercamiento a la lengua de señas, generando distintos niveles de competencia en ella. Se sugiere incorporar una visión social de la sorderaen el diagnóstico y proporcionar apoyo interdisciplinario a los padres durante este procesopara que puedan adquirir información sobre la lengua de señas y la Comunidad Sorda.
Sacco Based Financial Characteristics and Financial Performance of Deposit Taking Savings and Credit Co-operative Societies in Kenya
Authors: Carolyne Tarus , Simiyu Eddie
Published: September 2024

In Kenya, Deposit-Taking Savings and Credit Cooperative Societies have faced significant challenges that have adversely impacted their financial performance. While existing literature has linked financial performance to financial characteristics, there remain conceptual and contextual gaps in empirical research. These gaps prompted the current study to examine SACCO-based financial characteristics as a tool for enhancing the financial performance of DT-SACCOs in Kenya. The study employed a descriptive research design, targeting a population of 190 DT-SACCOs. Using purposive sampling, 181 SACCOs that had been operational since 2018 were selected for analysis. Secondary data from the period 2018 to 2023 were utilized, and a quantitative approach was applied to generate both descriptive and inferential statistics. Panel regression was used to estimate the direct relationship between SACCO-based financial characteristics and financial performance, while also appraising how the Sacco Societies Regulatory Authority risk regulations moderated this relationship. The study concluded that capital adequacy had a statistically significant positive effect on financial performance, indicating that stronger capital buffers enhance profitability. In contrast, asset quality and financial investments showed statistically significant negative effects, suggesting that poor loan quality and mismanaged investments negatively impact financial outcomes. Liquidity, however, was positively associated with financial performance, underscoring the importance of maintaining adequate liquidity reserves. Moreover, the relationship between SACCO-based financial characteristics and financial performance was significantly moderated by SASRA risk regulations, highlighting the critical role of regulatory oversight in shaping financial outcomes. Based on these findings, the study recommends that DT-SACCOs in Kenya should: maintain optimal capital adequacy levels to safeguard financial stability; prioritize careful asset quality management and regular loan monitoring to develop sound lending policies; optimize financial investments to ensure sufficient funding for operational expenses; and maintain adequate liquidity levels to meet financial obligations and improve overall performance.
Community Structure of Intertidal Macrofauna: Spatial Autocorrelation of Two Rocky Coasts of Gujarat, India
Authors: Dodiya Dimpal , Poriya Paresh
Published: September 2024

The present study describes the community structure of intertidal macrofauna on two rocky coasts of the Kathiawar Peninsula, Gujarat State. The results show significant spatial autocorrelation between the two study sites, with the Mantel correlogram identifying contrasting patterns of species distribution across the coasts. The Veraval coast shows a strong positive correlation owing to its rocky coastal regions. The homogeneity of the intertidal habitats leads to a diverse and cohesive macrofaunal community. In contrast, the Adri coast displays a negative correlation, attributed to the heterogeneous habitats of its intertidal zones. The combination of sandy and rocky patches creates a range of microhabitats, resulting in distinct ecological regions within the coast. This environmental variability promotes a more distinct and less uniform distribution of species. The study underscores the importance of conducting further ecological research on diverse marine ecosystems, particularly in areas with varied habitat types.
Anthropogenic Drivers of Floods and Household Adaptations Across the Coastal Wetland Areas of Limbe and Douala IV Municipalities, Cameroon
Authors: Fuanyi Aminkeng Lucienne , Sunjo Tata Emmanuel , N. Balgah Sounders , Buba Mohammadou Ousmanu
Published: September 2024

Many coastal wetland areas are experiencing the impacts of accelerated and episodic floods on the built environment and people’s livelihoods. This work examined the anthropogenic drivers of floods and household adaptations in Limbe and Douala IV Municipalities-Cameroon. Data was generated from primary and secondary sources and analysed using Statistical Package for Social Science version 26. Findings revealed that areas between 1-5m such as Clark’s Quarter, Down Beach, Mabanda and Ndobo witnessed severe floods. There was a statistically significant relationship between poor drainage facilities, haphazard settlement construction, blockage of drains by refuge and severe coastal flooding with probabilities values of (0.00582**, 0.0001*** and 0.0888*) respectively. Construction on raised foundation (p = 0.0439**), raising bed higher above the floor (p = 0.0370**), placement of valuable items above the floor (p = 0.0613*) and seasonal migration (p=0. 177) were principal informal adaptation strategies to floods. This study recommends proper land use planning by stakeholders.
Monitoring Land Use and Land Cover Change Through Earth Observation Datasets and Metric Analysis in the Barabanki District, Uttar Pradesh, India
Authors: Pal Akash , Kumar Mukesh , Suryavanshi Shakti , Kumar Neeraj , Wesley C. John , Lal Deepak
Published: September 2024

Land use and cover is the key environmental factors influencing the landscape. Changes in their composition are dynamic, widespread, and accelerating, driven primarily by natural phenomena and human activities. Timely and accurate information is a major challenge when assessing any landscape for future development. Remote sensing data, with its synoptic and multi-temporal characteristics, effectively bridges the gap by offering timely, accurate, and reliable information. The present study aimed to evaluate LULC change using Landsat satellite data within the Nindoora and Fatehpur blocks of Barabanki district, Lucknow, Uttar Pradesh. The study area covers approximately 59,498.78 ha. Landsat scenes recorded on November 10, 2013, and October 15, 2023, were acquired from the USGS website and subjected to geometric and radiometric corrections prior to analysis. The on-screen visual interpretation technique was employed to classify the satellite data into various land cover classes. The analysis identified five primary land use and land cover (LULC) classes: Water Bodies, Crops, Trees, Bare Ground, Rangeland, and Built-up Areas. In year 2013 Cropland emerged as the dominant land cover, occupying 88.34% of the total area followed by Built-up areas constitute 8.83% of the land. Whereas in year 2023 cropland occupy approximately 86.47% and Built-up areas constitute 10.70% of the land. This study underscores the complex interplay between agricultural productivity and urban expansion in Barabanki. These insights are essential for guiding future urban and environmental planning efforts in the region, offering a critical foundation for developing strategies that support both economic development and environmental sustainability.
Comparative Analysis of Biochar Derived from Rice Straw and Soybean Straw
Authors: B.O Iortyom, , R.E Kukwa , C.A Adah
Published: September 2024

Aim: Recycling agricultural postharvest waste and re-introducing it again into farmland is one of the tangible ways to address zero waste dream, soil infertility and climate change. Pyrolysis of crop leftovers into biochar remains the most acceptable alternative for proper management of crop waste. The possibility of sustainable biochar production practices and multi-functionality features makes it promising to fufill an increasing demand for soil amendment, agricultural sustainability, environmental protection, cutting-edge materials and mitigation of climate change.
Methodology: Same amount (14450 g) in feedstock of rice straw (RS) and soybean straw (SS) undergo slow pyrolysis separately to produce biochar. Physical (percentage yield, moisture, ash, volatile matter, bulk density, pH, electrical conductivity), chemical characterization (Microwave Plasma Atomic Emission Spectroscopy (MP-AES), Scanning Electron Microscope Energy Dispersive X-ray (SEM-EDX), Fourier Transformed Infrared (FTIR) and Thermogravimetric Analysis and Derivative Thermogravimetry (TGA and DTA)) and evaluation of bochar was determined.
Results: Rice straw biochar (RSB) recorded a higher char yield of 42.1%. Both lignocellulosic biochars were black and porous with a higher silica (10.6%) content in RSB and higher carbon (82.2%) content in SSB as was revealed by SEM-EDX. Higher ash 27.1%, volatile matter (VM) 31.3% and moisture 29.4% content was seen in RSB compared to SSB because of feedstock composition. Rice straw biochar show higher peaks of macro and micro mineral elements K(14561.21mg/kg), Ca (2401.28 mg/kg), and Na(1735.27 mg/kg) than soybean straw biochar. FTIR was used to identify functional groups that might act as cation adsorbents. As the temperature increased, the TGA and DTG graphs showed mass loss and sample breakdown.
Conclusion: Rice and soybean crop wastes were converted into biochar, a nutrient-rich material that maybe utilized to balance acidic soils promoting healthy plant growth and also protecting the environment.
Identification of Key Traits for Yield Improvement in Brinjal Through Correlation and Path Coefficient Analysis
Authors: Jakhwal Riya , Kumar Vipin , Kapoor Neelesh , Prakash Satya , Gupta Sneha , Singh Gunjan
Published: September 2024

Brinjal (Solanum melongena L.), also known as poor man’s vegetable, is widely distributed and grown in almost all parts of India. The assessment of genetic variation, correlation and path analysis for various yield and yield attributing traits in the available germplasm is crucial for selecting superior genotypes with desired traits such as yield, fruit quality, disease resistance, and adaptability to environmental conditions, thereby enhancing the potential for further crop improvement through breeding. Therefore, the present study was conducted to assess the phenotypic correlation and path coefficient among various yield and yield related traits for 42 genotypes of brinjal at the Horticulture Research Centre, SVPUA&T, Meerut (U.P.), India, over two consecutive Kharif seasons in 2022 and 2023 in Randomized Complete Block Design with three replications. The analysis of variance indicated significant variability across all the traits examined. In general, magnitudes of genotypic correlation coefficient were higher than their corresponding phenotypic correlation coefficient, implying a significant inherent relationship in different pair of traits. Based on the correlation coefficient analysis, fruit yield per plant had significant and positive association with fruit yield per plot, fruit yield per hectare, fruit weight, number of fruits per plant, fruit length and fruit girth both at genotypic and phenotypic levels. Path coefficient analysis showed that the traits viz., number of fruits per plant, fruit weight, fruit girth and fruit length exhibited highest direct effects on fruit yield and also indirectly influenced by the other yield contributing traits of brinjal. It is concluded from the study that these traits may be used as key indices towards the direct selection of elite genotypes for the successful breeding programme for yield improvement of brinjal germplasm.
Storage-related Haematological and Biochemical Changes in Sickle Cell Trait Donor Blood at Kisumu Regional Blood Transfusion Centre, Kenya
Authors: Meshack Shiundu , Michael Walekhwa , Caroline Mangare , Amos Mbugua
Published: September 2024

Background: Sickle cell trait (HbAS) donor blood, akin to normal hemoglobin (HbAA) blood, undergoes storage-induced hematological and biochemical changes that may impact its efficacy, safety, and viability. Detailed characterization of these changes in HbAS donors’ blood remains scarce. This study aimed to elucidate the storage-related hematological and biochemical changes in HbAS compared to HbAA donor blood.
Methods: The study used a prospective, laboratory-based experimental design. Sterile CPDA-anticoagulated blood (150 mL) was drawn into sample pouches attached to the main donor blood bags. Thirty units of HbAS and HbAA donor blood were analyzed for haematological and biochemical parameters. Assays for various parameters were performed at baseline and weekly intervals for four weeks. Statistical analyses were conducted using SPSS and R software, with one-way ANOVA applied to detect statistical differences. A P-value < 0.05 was considered statistically significant.
Results: Both sickle cell trait negative (HbAA) and positive (HbAS) donor blood showed notable changes. In HbAA blood, hemoglobin increased from 15.13 g/dL to 15.67 g/dL, hematocrit rose from 37.94% to 41.82%, hemolysis reached 0.54%, and platelet count dropped from 223.45 x 10⁹/L to 127.13 x 10⁹/L. For HbAS blood, hemoglobin rose from 13.78 g/dL to 15.12 g/dL,                       hematocrit increased from 40.98% to 45.07%, hemolysis hit 0.78%, and platelets dropped to 99.07 x 10⁹/L. LDH, potassium, and plasma bilirubin levels increased more sharply in HbAS blood than HbAA.
Conclusion: HbAS donor blood exhibits higher % hemolysis, more significant declines in RBC, PLT, and TWBC counts, and greater cellular degradation compared to HbAA donor blood.
Advancing Sustainable Sericulture: A Review on Biological Control Agents in Managing Pests and Diseases of Mulberry and Silkworms
Authors: S. M Kishore , Khajuria Marvi , K. S Shalini , Saini Ankit , Srivastav Shubham , K.S.N Manideep , M. N Chethan , Morabad Parvati B
Published: September 2024

Sericulture, the culture of rearing of silkworms (Bombyx mori L.) for silk production, is significantly impacted by pests and pathogens that affect silkworms and mulberry plants which is primary food source for these insects. Traditional chemical pesticides, though effective, pose risks including environmental pollution and harm to non-target organisms. To address these issues, the sericulture industry is increasingly adopting biological control methods, which utilize natural enemies such as parasitoids, predators and pathogens to manage pest populations in an eco-friendly manner. This approach offers several advantages: it minimizes environmental pollution, protects beneficial organisms and promotes sustainability by leveraging natural pest regulation mechanisms. Key biological control agents in sericulture include parasitoids like Acerophagus papayae and Trichogramma chilonis, predators such as ladybird beetles, and pathogens including fungal and bacterial species. Despite its benefits, biological control faces challenges such as slower action and environmental dependencies. Effective implementation requires careful planning, integration with other pest management strategies and ongoing monitoring. Overall, biological control represents a significant advancement towards more sustainable and resilient sericulture practices.
Linked changes in marine dissolved organic carbon molecular size and radiocarbon age
Authors: Walker B. D. , Primeau F. W. , Beaupré S. R. , Guilderson T. P. , Druffel E. R. M. , McCarthy M. D.
Published: October 2016

Marine dissolved organic carbon (DOC) is a major global carbon reservoir, yet its cycling remains poorly understood. Previous work suggests that DOC molecular size and chemical composition can significantly affect its bioavailability. Thus, DOC size and composition may control DOC cycling and radiocarbon age (via Δ14C). Here we show that DOC molecular size is correlated to DOC Δ14C in the Pacific Ocean. Our results, based on a series of increasing molecular size fractions from three depths in the Pacific, show increasing DOC Δ14C with increasing molecular size. We use a size‐age distribution model to predict the DOC and Δ14C of ultrafiltered DOC. The model predicts both large and small surface DOC with high Δ14C and a narrow range (200–500 Da) of low Δ14C DOC. Deep model offsets suggest different size distributions and/or Δ14C sources at 670–915 m. Our results suggest that molecular size and composition are linked to DOC reactivity and storage in the ocean.
Doubling of annual ammonia emissions from the peat fires in Indonesia during the 2015 El Niño
Authors: Whitburn S. , Van Damme M. , Clarisse L. , Turquety S. , Clerbaux C. , Coheur P.‐F
Published: October 2016

In the autumn of 2015, thousands of square kilometers of forest and peatlands in Indonesia went up in flames. Among the primary species emitted by fires, ammonia (NH3) is of special relevance for air quality. Here we derive daily and total NH3 emission fluxes over the affected area using satellite measurements for the years 2008–2015. The 2015 fires emitted an estimated 1.4–8.2 Tg of NH3 (with a maximum of 0.06–0.33 Tg d−1). On an annual basis, the 2015 NH3 emissions are a factor 2–3 larger than in the previous 7 years. We derive NH3 emission factors for peat soils, which are found to be 2.5–8 times lower than those used in the GFASv1.2 emission inventory but in excellent agreement with those reported in other recent studies. Finally, we estimate that 3.28 × 109 m3 peat soil was consumed during these 2015 fires, corresponding to an average burn depth of 39 cm.
The Circumglobal North American wave pattern and its relation to cold events in eastern North America
Authors: Harnik Nili , Messori Gabriele , Caballero Rodrigo , Feldstein Steven B.
Published: October 2016

Extreme large‐scale North American cold events are associated with strong undulations in the tropospheric jet stream which bring cold polar air southward over the continent. Here we propose that these jet undulations are associated with the North American part of the Circumglobal Teleconnection Pattern—a pair of zonally oriented waves of zonal wave number 5 which are in zonal quadrature with each other. While the Pacific/North American pattern is associated with the first circumglobal wave pattern, North American extreme cold events are associated with the second pattern. The 300 hPa meridional wind and surface temperature anomalies associated with the Circumglobal North American wave packet are similar to those associated with the strongest eastern U.S. cold events. Both types of events are associated with a wave packet propagating all the way from Asia across the Pacific and across North America, with cold temperature anomalies spreading southeastward from Canada over the continent.
Kelvin‐Helmholtz wave at the subsolar magnetopause boundary layer under radial IMF
Authors: Grygorov K. , Němeček Z. , Šafránková J. , Přech L. , Pi G. , Shue J.‐H.
Published: October 2016

We present the first observation of the Kelvin‐Helmholtz (KH) rolled‐up vortex at the dayside magnetopause layers under a radial interplanetary magnetic field (IMF). The study uses measurements of four Time History of Events and Macroscale Interactions during Substorms (THEMIS) probes aligned along the YGSE axis about 10 RE upstream of the Earth and located in different regions of the near‐Earth environment. THEMIS C and A serve as monitors of the quiet solar wind and fluctuating magnetosheath conditions, respectively, and THEMIS D and E observe the magnetopause and low‐latitude boundary layer (LLBL) crossings. The analysis shows the following: (1) a radial IMF changes to the southward pointing magnetosheath magnetic field; (2) dayside reconnection forms the thin but dense LLBL; (3) a large velocity shear at the LLBL inner edge excites a train of KH waves; and (4) in spite of a short path from the subsolar point (≈5 RE), one of the KH waves exhibits all features of a fully developed rolled‐up vortex.
Estimating methane emissions in California's urban and rural regions using multitower observations
Authors: Jeong Seongeun , Newman Sally , Zhang Jingsong , Andrews Arlyn E. , Bianco Laura , Bagley Justin , Cui Xinguang , Graven Heather , Kim Jooil , Salameh Peter , LaFranchi Brian W. , Priest Chad , Campos‐Pineda Mixtli , Novakovskaia Elena , Sloop Christopher D. , Michelsen Hope A. , Bambha Ray P. , Weiss Ray F. , Keeling Ralph , Fischer Marc L.
Published: October 2016

We present an analysis of methane (CH4) emissions using atmospheric observations from 13 sites in California during June 2013 to May 2014. A hierarchical Bayesian inversion method is used to estimate CH4 emissions for spatial regions (0.3° pixels for major regions) by comparing measured CH4 mixing ratios with transport model (Weather Research and Forecasting and Stochastic Time‐Inverted Lagrangian Transport) predictions based on seasonally varying California‐specific CH4 prior emission models. The transport model is assessed using a combination of meteorological and carbon monoxide (CO) measurements coupled with the gridded California Air Resources Board (CARB) CO emission inventory. The hierarchical Bayesian inversion suggests that state annual anthropogenic CH4 emissions are 2.42 ± 0.49 Tg CH4/yr (at 95% confidence), higher (1.2–1.8 times) than the current CARB inventory (1.64 Tg CH4/yr in 2013). It should be noted that undiagnosed sources of errors or uncaptured errors in the model‐measurement mismatch covariance may increase these uncertainty bounds beyond that indicated here. The CH4 emissions from the Central Valley and urban regions (San Francisco Bay and South Coast Air Basins) account for ~58% and 26% of the total posterior emissions, respectively. This study suggests that the livestock sector is likely the major contributor to the state total CH4 emissions, in agreement with CARB's inventory. Attribution to source sectors for subregions of California using additional trace gas species would further improve the quantification of California's CH4 emissions and mitigation efforts toward the California Global Warming Solutions Act of 2006 (Assembly Bill 32).
Early Disease Activity or Clinical Response as Predictors of Long‐Term Outcomes With Certolizumab Pegol in Axial Spondyloarthritis or Psoriatic Arthritis
Authors: van der Heijde D. , Deodhar A. , Fleischmann R. , Mease P. J. , Rudwaleit M. , Nurminen T. , Davies O.
Published: October 2016

Objective

Early identification of patients unlikely to achieve good long‐term disease control with anti–tumor necrosis factor therapy in axial spondyloarthritis (SpA) and psoriatic arthritis (PsA) is important for physicians following treat‐to‐target recommendations. Here we assess associations between disease activity or clinical response during the first 12 weeks of treatment and attainment of treatment targets at week 48 in axial SpA and PsA patients receiving certolizumab pegol.

Methods

The relationship between disease activity or clinical response during the first 12 weeks of treatment and achievement of week‐48 targets (for axial SpA: inactive disease based on Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C‐reactive protein [CRP] level, or Bath Ankylosing Spondylitis Disease Activity Index <2 with normal CRP level; and for PsA: minimal disease activity) was assessed post hoc using RAPID‐axSpA and RAPID‐PsA trial data.

Results

A clear relationship between disease activity from week 2 to 12 and achievement of week‐48 treatment targets was observed in both axial SpA and PsA populations. In axial SpA, week‐48 ASDAS inactive disease was achieved by 0% of patients (0 of 21) with ASDAS very high disease activity at week 12, compared to 68% of patients (34 of 50) with week‐12 ASDAS inactive disease. For PsA, week‐48 minimal disease activity was achieved by 0% of patients (0 of 26) with Disease Activity Score in 28 joints (DAS28) using the CRP level >5.1 at week 12, compared to 73% of patients (57 of 78) with DAS28‐CRP <2.6. Similar results were observed regardless of the disease activity measure used. Clinical response at week 12 also predicted week‐48 outcomes, though to a lesser extent than disease activity.

Conclusion

Using disease activity and the clinical response state during the first 12 weeks of certolizumab pegol treatment, it was possible to identify a subset of axial SpA and PsA patients unlikely to achieve long‐term treatment goals.
Effect of Disease Activity, Glucocorticoid Exposure, and Rituximab on Body Composition During Induction Treatment of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Wallace Zachary S. , Miloslavsky Eli M. , Cascino Matthew , Unizony Sebastian H. , Lu Na , Hoffman Gary S. , Kallenberg Cees G. M. , Langford Carol A. , Merkel Peter A. , Monach Paul A. , Seo Philip , Spiera Robert , St.Clair E. William , Specks Ulrich , Brunetta Paul , Choi Hyon K. , Stone John H.
Published: October 2016

Objective

We investigated the relationships between glucocorticoid use, disease activity, and changes in body mass index (BMI) in patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV).

Methods

We analyzed AAV patients enrolled in the Rituximab in AAV trial. Glucocorticoid use, BMI, and disease activity were measured regularly during the trial period. We performed mixed‐effects regressions to examine the associations of time‐dependent cumulative average glucocorticoid use and disease activity with changes in BMI over time, while adjusting for potential confounders.

Results

The mean ± SD baseline BMI of the 197 patients enrolled was 28.8 ± 6.3 kg/m2. Patients with newly diagnosed AAV tended to have a lower mean ± SD BMI than those with relapsing disease (28.0 ± 5.7 kg/m2 versus 29.6 ± 6.8 kg/m2) and higher disease activity (mean ± SD Birmingham Vasculitis Activity Score for Wegener's Granulomatosis 8.7 ± 3.3 versus 7.4 ± 2.7). The most significant change in BMI occurred during the first 6 months of the trial (mean ± SD increase of 1.1 ± 2.2 kg/m2; P < 0.0001). Disease activity improvement, glucocorticoid exposure, and randomization to rituximab were each independently associated with an increase in BMI (P < 0.001 for all analyses).

Conclusion

Our findings suggest that changes in BMI, as well as glucocorticoid exposure, are independently associated with improvements in disease activity in AAV. Rituximab may also have effects on BMI independent of its impact on disease activity.
Disease Activity During Pregnancy and the First Year Postpartum in Women With Systemic Lupus Erythematosus
Authors: Götestam Skorpen Carina , Lydersen Stian , Gilboe Inge‐Margrethe , Skomsvoll Johan Fredrik , Salvesen Kjell Å , Palm Øyvind , Koksvik Hege Suorza Svean , Jakobsen Bente , Wallenius Marianne
Published: October 2016

Objective

Disease activity measured by validated methods has been sparsely examined during and after pregnancy in women with systemic lupus erythematosus (SLE). The aim of this study was to describe the longitudinal course of disease activity during pregnancy and the first year postpartum using the Lupus Activity Index in Pregnancy (LAI‐P).

Methods

RevNatus is a nationwide Norwegian prospective observational register including women diagnosed with inflammatory rheumatic diseases. LAI‐P is a modified version of the LAI, with a good ability to assess disease activity in pregnant women with SLE. These indexes were used to assess disease activity at 6 visits (in trimesters 1, 2, and 3, and at 6 weeks, 6 months, and 12 months postpartum). The longitudinal course of disease activity was analyzed using an ordinal logistic mixed model.

Results

A total of 757 visits (145 pregnancies) in women with SLE were included in the analysis. More than half (51.6%) of the disease activity scores indicated remission, and only 6.3% indicated moderate disease activity. The model showed a statistically significant and clinically relevant change in disease activity over time, and a higher disease activity 6 and 12 months postpartum compared to the third trimester and 6 weeks postpartum.

Conclusion

The majority of women had low or no disease activity at conception and during pregnancy, with higher disease activity at 6 and 12 months after delivery. This points to the importance of tight disease control not only before and during pregnancy but also in the first year postpartum.
Cyclic mass transport phenomena in a novel reactor for gas–liquid–solid contacting
Authors: Gelhausen Marius G. , Yang Shaoquan , Cegla Maximilian , Agar David W.
Published: October 2016

This study introduces a novel reactor concept, referred to as the Siphon Reactor, for intensified phase contacting of gas–liquid reactants on heterogeneous catalysts. The reactor comprises a fixed catalyst bed in a siphoned reservoir, which is periodically filled and emptied. This serves to alternate liquid–solid and then gas–liquid mass transfer processes. As the duration of each phase can be manipulated, mass transfer can be deliberately harmonized with the reaction. Residence time experiments demonstrate that, in contrast to periodically operated trickle‐bed reactors, the static liquid hold‐up is exchanged frequently and uniformly due to the complete homogeneous liquid wetting. A mathematical model describing the siphon hydrodynamics was developed and experimentally validated. The model was extended to account for a heterogeneously catalyzed gas–liquid reaction and capture the influence of siphon operation on conversion and selectivity of a consecutive reaction. © 2016 American Institute of Chemical Engineers AIChE J, 63: 208–215, 2017
Highly polygenic architecture of antidepressant treatment response: Comparative analysis of SSRI and NRI treatment in an animal model of depression
Authors: Malki Karim , Tosto Maria Grazia , Mouriño‐Talín Héctor , Rodríguez‐Lorenzo Sabela , Pain Oliver , Jumhaboy Irfan , Liu Tina , Parpas Panos , Newman Stuart , Malykh Artem , Carboni Lucia , Uher Rudolf , McGuffin Peter , Schalkwyk Leonard C. , Bryson Kevin , Herbster Mark
Published: October 2016

Response to antidepressant (AD) treatment may be a more polygenic trait than previously hypothesized, with many genetic variants interacting in yet unclear ways. In this study we used methods that can automatically learn to detect patterns of statistical regularity from a sparsely distributed signal across hippocampal transcriptome measurements in a large‐scale animal pharmacogenomic study to uncover genomic variations associated with AD. The study used four inbred mouse strains of both sexes, two drug treatments, and a control group (escitalopram, nortriptyline, and saline). Multi‐class and binary classification using Machine Learning (ML) and regularization algorithms using iterative and univariate feature selection methods, including InfoGain, mRMR, ANOVA, and Chi Square, were used to uncover genomic markers associated with AD response. Relevant genes were selected based on Jaccard distance and carried forward for gene‐network analysis. Linear association methods uncovered only one gene associated with drug treatment response. The implementation of ML algorithms, together with feature reduction methods, revealed a set of 204 genes associated with SSRI and 241 genes associated with NRI response. Although only 10% of genes overlapped across the two drugs, network analysis shows that both drugs modulated the CREB pathway, through different molecular mechanisms. Through careful implementation and optimisations, the algorithms detected a weak signal used to predict whether an animal was treated with nortriptyline (77%) or escitalopram (67%) on an independent testing set. The results from this study indicate that the molecular signature of AD treatment may include a much broader range of genomic markers than previously hypothesized, suggesting that response to medication may be as complex as the pathology. The search for biomarkers of antidepressant treatment response could therefore consider a higher number of genetic markers and their interactions. Through predominately different molecular targets and mechanisms of action, the two drugs modulate the same Creb1 pathway which plays a key role in neurotrophic responses and in inflammatory processes. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.
Studies on kinetics and thermodynamics of Cr(VI) adsorption onto sand to check feasibility of its use as tracer in oilfields
Authors: Balikram Archana , Ojha Keka
Published: October 2016

The present investigation is aimed to evaluate the adsorption kinetics and its thermodynamics of Cr(VI) on sand. Effects of various parameters like pH, adsorbent dosages, adsorbate loading, concentration, contact time, and temperature were studied in detail. Among different kinetic models such as pseudo‐first‐order, pseudo‐second‐order, and intra‐particle diffusion, pseudo‐second‐order kinetics was found to fit best. The Langmuir isotherm adsorption model could describe the adsorption isotherm best compared to the other models. From the results, it was observed that adsorption of Cr(VI) was reduced to a negligible value at temperature > 50 °C and increased salinity, which specifies the feasibility of its application as tracer at reservoir condition. © 2016 Curtin University of Technology and John Wiley & Sons, Ltd.
Comparative Assessment of the Different American College of Rheumatology/European League Against Rheumatism Remission Definitions for Rheumatoid Arthritis for Their Use as Clinical Trial End Points
Authors: Mack Michael E. , Hsia Elizabeth , Aletaha Daniel
Published: October 2016

Objective

The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have defined remission using Boolean‐ or index‐based criteria (i.e., a Simplified Disease Activity Index [SDAI] score of ≤3.3). We undertook this study to compare definitions of remission to inform choice of end points for future rheumatoid arthritis (RA) clinical trials, and we also included in our comparison the remission criterion of a score of ≤2.8 on the Clinical Disease Activity Index (CDAI).

Methods

We performed post hoc analyses on clinical remission rates using data from 2 infliximab trials (the ASPIRE [Active‐Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset] and ATTRACT [Anti–Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy] trials) and 1 golimumab trial (the GO‐FORWARD trial). We investigated stringency of the different remission definitions, their power to discriminate between active drug and comparator, and aspects of their internal and external validity. We also investigated population determinants of discriminatory power for a particular remission end point.

Results

In patients with early RA (the ASPIRE trial), ACR/EULAR Boolean, CDAI, and SDAI remission rates at 6–7 months were 4–6% for methotrexate (MTX) alone versus 11–14% for infliximab plus MTX. In patients with MTX‐refractory active RA (the ATTRACT and GO‐FORWARD trials), remission rates were ≤1% for comparator (add‐on of placebo) versus 4–6% for add‐on of infliximab in the ATTRACT trial and ≤3% for comparator (add‐on of placebo) versus 11–13% for add‐on of golimumab in the GO‐FORWARD trial. Existing remission cut points of different measures were generally comparable, with the Boolean criteria being somewhat more stringent than the SDAI and CDAI criteria. Remission rates were similar across definitions, as was average statistical power (CDAI, 55.6%; Boolean, 59.9%; SDAI, 62.6%).

Conclusion

Remission is an ambitious primary end point for RA clinical trials, to be reserved for selected scenarios based on power considerations. The ACR/EULAR definitions are interchangeable, with slightly higher stringency of Boolean criteria over index‐based criteria.
Atazanavir increases the plasma concentrations of 1200 mg raltegravir dose
Authors: Krishna Rajesh , East Lilly , Larson Patrick , Valiathan Chandni , Deschamps Kathleen , Luk Julie Ann , Bethel‐Brown Crystal , Manthos Helen , Brejda John , Gartner Michael
Published: October 2016

Raltegravir is a human immunodeficiency virus (HIV)‐1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice‐daily (b.i.d.). Raltegravir 1200 mg once‐daily (q.d.) (investigational q.d. formulation of 2 × 600 mg tablets; q.d. RAL) was found to be generally well tolerated and non‐inferior to the marketed 400 mg b.i.d. dose at 48 weeks in a phase 3 trial. Since raltegravir is eliminated mainly by metabolism via a uridine diphosphate glucuronosyltransferase (UGT) 1A1‐mediated glucuronidation pathway, co‐administration of UGT1A1 inhibitors may increase the plasma levels of q.d. RAL. To assess this potential, the drug interaction of 1200 mg raltegravir using atazanavir, a known UGT1A1 inhibitor, was studied. An open‐label, randomized, 2‐period, fixed‐sequence phase 1 study was performed in adult healthy male and female (non‐childbearing potential) subjects ≥ 19 and ≤ 55 years of age, with a body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2. Subjects (n = 14) received a single oral dose of 1200 mg raltegravir in period 1. After a washout period of at least 7 days, the subjects received oral doses of 400 mg atazanavir q.d. for 9 consecutive days, with a single oral dose of 1200 mg raltegravir co‐administered on day 7 of period 2. Serial blood samples were collected for 72 h following raltegravir dosing and analysed using a validated bioanalytical method to quantify raltegravir plasma concentrations. Co‐administration with atazanavir yielded GMRs (90% CIs) for raltegravir AUC0‐∞, Cmax and C24 of 1.67 (1.34, 2.10), 1.16 (1.01, 1.33) and 1.26 (1.08, 1.46), respectively. There was no effect of raltegravir on serum total bilirubin. In contrast, atazanavir increased the mean bilirubin by up to 200%, an effect that was preserved in the atazanavir/raltegravir treatment group. Administration of single q.d. RAL alone and co‐administered with multiple oral doses of atazanavir were generally well tolerated in healthy subjects. The results show that atazanavir increased the PK exposure of raltegravir; therefore, co‐administration of atazanavir with raltegravir q.d. is not recommended. Copyright © 2016 John Wiley & Sons, Ltd.
Silk scaffolds connected with different naturally occurring biomaterials for prostate cancer cell cultivation in 3D
Authors: Bäcker Anne , Erhardt Olga , Wietbrock Lukas , Schel Natalia , Göppert Bettina , Dirschka Marian , Abaffy Paul , Sollich Thomas , Cecilia Angelica , Gruhl Friederike J.
Published: October 2016

In the present work, different biopolymer blend scaffolds based on the silk protein fibroin from Bombyx mori (BM) were prepared via freeze‐drying method. The chemical, structural, and mechanical properties of the three dimensional (3D) porous silk fibroin (SF) composite scaffolds of gelatin, collagen, and chitosan as well as SF from Antheraea pernyi (AP) and the recombinant spider silk protein spidroin (SSP1) have been systematically investigated, followed by cell culture experiments with epithelial prostate cancer cells (LNCaP) up to 14 days. Compared to the pure SF scaffold of BM, the blend scaffolds differ in porous morphology, elasticity, swelling behavior, and biochemical composition. The new composite scaffold with SSP1 showed an increased swelling degree and soft tissue like elastic properties. Whereas, in vitro cultivation of LNCaP cells demonstrated an increased growth behavior and spheroid formation within chitosan blended scaffolds based on its remarkable porosity, which supports nutrient supply matrix. Results of this study suggest that silk fibroin matrices are sufficient and certain SF composite scaffolds even improve 3D cell cultivation for prostate cancer research compared to matrices based on pure biomaterials or synthetic polymers.