Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK.

Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting. Methods: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey. Results: 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD. Conclusion: We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting.

Exposure to metals and the disruption of sex hormones in 6-19 years old children: An exploration of mixture effects.

BACKGROUND: Individual metals have been linked to sex hormones disruption, but the associations of metals mixture are rarely examined among children. METHODS: A total of 1060 participants of 6-19-year-old who participated in the National Health and Nutrition Examination Survey (2013-2016) were included. Eighteen metals were quantified in the whole blood and urine. Sex hormones were measured in serum, including total testosterone (TT), estradiol (E2), and sex hormone binding globulin (SHBG). In addition, free androgen index (FAI) and the ratio of TT to E2 were calculated. Bayesian kernel machine regression and latent class analysis were performed to assess the associations of metals mixture and exposure patterns of metals at varied levels with sex hormones while adjusting for selected covariates. All analyses were conducted by sex-age and sex-puberty groups to explore the potential sex-dimorphic effects. RESULTS: Exposure to metals mixture was associated with elevated levels of FAI and E2 among 12-19 years old girls. Moreover, the exposure pattern of metals that was characterized by high levels of blood and urinary cadmium, blood manganese, and urinary cobalt was associated with elevated E2 and reduced TT/E2 levels among girls of 12-19 years old. However, the associations of metals mixture with sex hormones were overall nonsignificant among boys. Nevertheless, metals exposure pattern that was characterized by high levels of blood lead, urinary barium, strontium, and lead but comparatively low levels of the other metals was consistently associated with reduced levels of FAI and E2 but elevated levels of TT/E2 and SHBG among boys of 12-19 years old. CONCLUSION: Metals mixture and exposure patterns that were dominated by high levels of certain metals were associated with sex hormones imbalance among 12-19 years old children in a sex-dimorphic pattern, with the identified individual metals that drove the associations of metals mixture varied by sex.

Bilateral synchronous multiple lung cancer: an emerging problem.

Aim: Multiple primary lung cancers are becoming increasingly recognised and pose diagnostic and staging uncertainties with challenging management options and prognostication. Case report: We describe a case of synchronous multiple primary lung cancer occurring bilaterally, and the steps in reaching the diagnosis, initial surgical management, the intensive follow-up this underwent, and how its subsequent recurrence led to treatment with radiation therapy in light of the patient's declining fitness. Discussion: This case highlighted that cytological recurrence could occur prior to radiological recurrence, especially for endobronchial tumors, and intensive follow-up both radiologically and endoscopically with multidisciplinary input is crucial in the management of these challenging cases where evidence-based guidelines are limited.

This article discusses an unusual presentation of two separate lung cancer occurring in both lungs at the same time, how it was treated in the first instance, and the difficulties encountered by the clinical team during the post-treatment monitoring period. After initial treatment with surgery, the patient underwent a period of monitoring through CT scans and camera tests into the lungs to visually assess the treated areas, with managed to detect that the cancer came back at an early stage. With further surgery not being a viable option, radiation therapy was used instead to manage this recurrence. This report demonstrates the importance of close monitoring of these types of lung cancers following treatment with a multidisciplinary approach given their unusual nature and lack of available evidence to guide treatment, in order to achieve a successful outcome for the patient.

Seamount effect on phytoplankton biomass and community above a deep seamount in the tropical western Pacific.

It is generally believed that the enhancement of phytoplankton appears only in shallow and intermediate depth seamounts, while the phenomenon has also been observed in some deep seamounts by satellites recently. To figure out what effect do deep seamounts have on phytoplankton and the relevant mechanisms, the phytoplankton biomass and community on the Kocebu Seamount (depth: 1198 m) were studied. The results showed that the average Chl a concentration of the seamount was 0.09 mg·m-3, and the Chl a maximum layer was mainly located at 150 m, and picophytoplankton such as prochlorophytes and cyanobacteria were the dominant groups. High Chl a patches (>0.2 mg·m-3) were mainly distributed within 20 km of the peak, and both nitrate and orthophosphate were obviously uplifted at the peak. The physical data indicated the uplifted of nutrients could be caused by the internal tides, which generated by the interaction of topography and tide. This is the first time that the promotion of phytoplankton was observed in situ on a deep seamount, and this study expounded relevant mechanisms and suggested that the ecological functions of deep seamounts may have been previously neglected.

LncRNA HOTAIR modulates chondrocyte apoptosis and inflammation in osteoarthritis via regulating miR-1277-5p/SGTB axis.

Osteoarthritis (OA) is a common degenerative joint disease in the elderly. This study aimed to investigate the role and mechanism of lncRNA HOX transcript antisense RNA (HOTAIR) in lipopolysaccharide (LPS)-treated chondrocytes in OA. CHON-001 chondrocytes treated with LPS were used as a cell model of OA. The levels of HOTAIR, miR-1277-5p and small glutamine rich tetratricopeptide repeat containing beta (SGTB) were measured via quantitative real-time polymerase chain reaction or western blot. Cell viability and apoptosis were assessed using Cell Counting Kit-8 and flow cytometry. The levels of inflammation-related factors were examined via enzyme-linked immunosorbent assay (ELISA). Aggrecan and Collagen II protein levels were detected using western blot. The interaction among HOTAIR, miR-1277-5p and SGTB were validated by dual-luciferase reporter analysis. HOTAIR and SGTB were up-regulated, while miR-1277-5p was down-regulated in OA cartilages and LPS-stimulated CHON-001 chondrocytes. HOTAIR depletion inhibited LPS-induced apoptosis and inflammation in chondrocytes. Moreover, down-regulation of HOTAIR attenuated LPS-triggered chondrocyte apoptosis and inflammation via sponging miR-1277-5p. Also, miR-1277-5p repressed LPS-induced chondrocyte apoptosis and inflammation by targeting SGTB. Furthermore, HOTAIR enhanced SGTB expression by sponging miR-1277-5p. HOTAIR aggravated chondrocyte apoptosis and inflammation in OA via regulating miR-1277-5p/SGTB pathway.

Abdominal cavity unidirectional shunt for refractory pericardial effusion 7 months after cardiac valve replacement: A case report.

Refractory pericardial effusion after repeated pericardial drainage and drug therapy for nearly half a year after cardiac valve replacement is rare. We present the case of a 36-year-old female patient who underwent an abdominal cavity unidirectional shunt for refractory massive pericardial effusion through a subxiphoid mini-incision, 7 months after cardiac valve replacement. The head end of a prefabricated bovine pericardial short tube with double leaflets on the tail was sutured to the small incised hole of the diaphragm, whereas the body and the tail of the short tube were dissociated in the left anterior hepatic space. Three months later, the pericardial effusion completely disappeared, no peritoneal effusion occurred, and all symptoms vanished.

The Performances of Hyperspectral Sensors for Proximal Sensing of Nitrogen Levels in Wheat.

The accurate and high throughput quantification of nitrogen (N) content in wheat using non-destructive methods is an important step towards identifying wheat lines with high nitrogen use efficiency and informing agronomic management practices. Among various plant phenotyping methods, hyperspectral sensing has shown promise in providing accurate measurements in a fast and non-destructive manner. Past applications have utilised non-imaging instruments, such as spectrometers, while more recent approaches have expanded to hyperspectral cameras operating in different wavelength ranges and at various spectral resolutions. However, despite the success of previous hyperspectral applications, some important research questions regarding hyperspectral sensors with different wavelength centres and bandwidths remain unanswered, limiting wide application of this technology. This study evaluated the capability of hyperspectral imaging and non-imaging sensors to estimate N content in wheat leaves by comparing three hyperspectral cameras and a non-imaging spectrometer. This study answered the following questions: (1) How do hyperspectral sensors with different system setups perform when conducting proximal sensing of N in wheat leaves and what aspects have to be considered for optimal results? (2) What types of photonic detectors are most sensitive to N in wheat leaves? (3) How do the spectral resolutions of different instruments affect N measurement in wheat leaves? (4) What are the key-wavelengths with the highest correlation to N in wheat? Our study demonstrated that hyperspectral imaging systems with satisfactory system setups can be used to conduct proximal sensing of N content in wheat with sufficient accuracy. The proposed approach could reduce the need for chemical analysis of leaf tissue and lead to high-throughput estimation of N in wheat. The methodologies here could also be validated on other plants with different characteristics. The results can provide a reference for users wishing to measure N content at either plant- or leaf-scales using hyperspectral sensors.

The seamount effect on phytoplankton in the tropical western Pacific.

The tropical western Pacific, one of the most oligotrophic seas on Earth, has a large number of seamounts. In this sea, we hypothesize that although the presence of shallow seamounts can enhance phytoplankton biomass, they do not alter the phytoplankton community composition. The concentration and distribution of size-fractionated chlorophyll a (Chl a) on the C4 Seamount were measured, and the phytoplankton community was analyzed based on photosynthetic pigments. The results showed that the deep chlorophyll maximum (DCM) was located between 100 and 150 m and that picophytoplankton such as prochlorophytes and cyanobacteria (mainly Synechococcus) were the dominant groups, contributing approximately 85% of the Chl a. The integrated Chl a concentration above the seamount was significantly higher than that off the seamount, and most communities were enhanced near the peak. The physical, chemical, and biological coupling processes of the C4 Seamount support the classic hypothesis of the seamount effect. However, the relative contributions of different phytoplankton groups to Chl a were not significantly different between stations above and off the seamount, and the analysis of similarities among results also indicated that the community composition on the C4 Seamount did not differ significantly from that off the seamount. In addition, size-fractionated Chl a data from two nearby shallow seamounts also supported our hypothesis. More studies on the ecology of seamounts in the tropical western Pacific are required to further confirm and refine these results.

Alteration of N6-methyladenosine epitranscriptome profile in unilateral ureteral obstructive nephropathy.

Aim: To reveal the alterations of N6-methyladenosine (m6A) epitranscriptome profile in kidney after unilateral ureteral obstruction in mice. Materials & methods: Total renal m6A and expressions of methyltransferases and demethylases were detected by colorimetric quantification method, real-time PCR and western blot, respectively. Methylated RNA immunoprecipitation sequencing was performed to map epitranscriptome-wide m6A profile. Results: Total m6A levels were time-dependent decreased within 1 week, with the lowest level detected at day 7. A total of 823 differentially methylated transcripts in 507 genes were identified. Specifically, demethylated mRNAs selectively acted on multiple pathways, including TGF-ß and WNT. Conclusion: m6A modification has a functional importance in renal interstitial fibrosis during obstructive nephropathy and might be a promising therapeutic target.

A benchmark dataset for ensemble framework by using nature inspired algorithms for the early-stage forest fire rescue.

This paper introduces a benchmark dataset to the research article entitled "Ensemble framework by using nature inspired algorithms for the early-stage forest fire rescue - a case study of dynamic optimization problems", by Zhang et al. [7]. Rescue ensemble that consists of rescue simulator and rescue algorithm is characterized by supporting the dynamic simulation of forest fire rescue. The purpose of rescue algorithm is to minimize the longest flight time of aircraft group II and the newly-increased burnt forest cost in one period, simultaneously. The map information in our dataset is from Google map and relevant parameters are also from the actual situation data. The benchmark contains 10 different maps that researchers can use to evaluate their own algorithms and compare their performance with our algorithm.

The Development of Hyperspectral Distribution Maps to Predict the Content and Distribution of Nitrogen and Water in Wheat (Triticum aestivum).

Quantifying plant water content and nitrogen levels and determining water and nitrogen phenotypes is important for crop management and achieving optimal yield and quality. Hyperspectral methods have the potential to advance high throughput phenotyping efforts by providing a rapid, accurate, and nondestructive alternative for estimating biochemical and physiological plant traits. Our study (i) acquired hyperspectral images of wheat plants using a high throughput phenotyping system, (ii) developed regression models capable of predicting water and nitrogen levels of wheat plants, and (iii) applied the regression coefficients from the best-performing models to hyperspectral images in order to develop prediction maps to visualize nitrogen and water distribution within plants. Hyperspectral images were collected of four wheat (Triticum aestivum) genotypes grown in nine soil nutrient conditions and under two water treatments. Five multivariate regression methods in combination with 10 spectral preprocessing techniques were employed to find a model with strong predictive performance. Visible and near infrared wavelengths (VNIR: 400-1,000nm) alone were not sufficient to accurately predict water and nitrogen content (validation R2 = 0.56 and R2 = 0.59, respectively) but model accuracy was improved when shortwave-infrared wavelengths (SWIR: 1,000-2,500nm) were incorporated (validation R2 = 0.63 and R2 = 0.66, respectively). Wavelength reduction produced equivalent model accuracies while reducing model size and complexity (validation R2 = 0.69 and R2 = 0.66 for water and nitrogen, respectively). Developed distribution maps provided a visual representation of the concentration and distribution of water within plants while nitrogen maps seemed to suffer from noise. The findings and methods from this study demonstrate the high potential of high-throughput hyperspectral imagery for estimating and visualizing the distribution of plant chemical properties.

Experimental study on the compressive strength, damping and interfacial transition zone properties of modified recycled aggregate concrete.

At present, many modification methods have been proposed to improve the performance of recycled aggregate concrete (RAC). In this study, tests on the compressive strength and damping properties of modified RAC with the addition of different proportions of recycled coarse aggregate (RCA) (0, 50, 100%), rubber powder (10, 15, 20%), steel fibre (5, 7.5, 10%) and fly ash (15, 20, 5%) are carried out. To elucidate the effect of the modification method on the interfacial transition zone (ITZ) performance of RAC, model ITZ specimens are used for push-out tests. The results show that when the replacement rate of RCA reaches 100%, the loss factor of the RAC is 6.0% higher than that of natural aggregate concrete; however, the compressive strength of the RAC decreases by 22.6%. With the addition of 20% rubber powder, the damping capacity of the modified RAC increases by 213.7%, while the compressive strength of the modified RAC decreases by 47.5%. However, with the addition of steel fibre and fly ash, both the compressive strength and loss factor of the RAC specimens increase. With a steel fibre content of 10 wt%, the compressive strength and loss factor of the RAC increase by 21.9% and 15.2%, respectively. With a fly ash content of 25 wt%, the compressive strength and loss factor of the RAC increase by 8.6% and 6.9%, respectively. This demonstrates that steel fibre and fly ash are effective in improving both the damping properties and compressive strength of RAC, and steel fibre is more effective than fly ash. Two methods were used for modification of the RAC: reinforcing the RCA through impregnation with a 0.5% polyvinyl alcohol (PVA) emulsion and nano-SiO2 solution, and strengthening the RAC integrally through the addition of fly ash as an admixture. Both of these techniques can improve the ITZ bond strength between the RAC and new mortar. Replacing 10% of the cement with fly ash in the new mortar is shown to be the best method to improve the ITZ strength.

Transformation of a high-dimensional color space for material classification.

Images in red-green-blue (RGB) color space need to be transformed to other color spaces for image processing or analysis. For example, the well-known hue-saturation-intensity (HSI) color space, which separates hue from saturation and intensity and is similar to the color perception of humans, can aid many computer vision applications. For high-dimensional images, such as multispectral or hyperspectral images, transformation images to a color space that can separate hue from saturation and intensity would be useful; however, the related works are limited. Some methods could interpret a set of high-dimensional images to hue, saturation, and intensity, but these methods need to reduce the dimension of original images to three images and then map them to the trichromatic color space of RGB. Generally, dimension reduction could cause loss or distortion of original data, and, therefore, the transformed color spaces could not be suitable for material classification in critical conditions. This paper describes a method that can transform high-dimensional images to a color space called hyper-hue-saturation-intensity (HHSI), which is analogous to HSI in high dimensions. The transformation does not need dimension reduction, and, therefore, it can preserve the original information. Experimental results indicate that the hyper-hue is independent of saturation and intensity and it is more suitable for material classification of proximal or remote sensing images captured in a natural environment where illumination usually cannot be controlled.

Abnormally high phytoplankton biomass near the lagoon mouth in the Huangyan Atoll, South China Sea.

Nutrient concentration and phytoplankton biomass were investigated in Huangyan Atoll in May 2015. The concentrations of nutrients were very low, and dissolved inorganic nitrogen was composed mainly of ammonia. Nitrogen likely was the primary limiting factor for phytoplankton growth. The spatial variation of phytoplankton biomass was significant among the lagoon, reef flats, and outer reef slopes. Extremely high chlorophyll a concentration and micro-phytoplankton abundance were found in the region near the lagoon mouth. This high phytoplankton biomass might be due to nutrient input from fishing vessels and phytoplankton aggregation driven by the southwestern wind. Our results indicate that phytoplankton biomass could be a reliable indicator of habitat differences in this coral reef ecosystem, and micro-phytoplankton seems to be more sensitive to nutrient input than pico-phytoplankton.

N-[(E)-4-(Methyl-sulfon-yl)benzyl-idene]-3-nitro-aniline.

In the title compound, C(14)H(12)N(2)O(4)S, the dihedral angle between the two aromatic rings is 35.65 (12)°. The crystal packing is stabilized by weak C-H⋯O hydrogen bonds and aromatic π-π ring stacking inter-actions [minimum ring centroid separation = 3.697 (3) Å].