bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cupola: an additional layer of protection for providers working in the oropharyngeal region
Authors: Villa Alessandro , Grenon Marlene
Published: March 2021

Objectives

To reduce the spread of the infection, especially during aerosol generating procedures, we invented “The Cupola”, a shield that creates a mechanical barrier around the patient’s head and body. With this pilot study we aimed to assess the effectiveness of an additional layer of protection (The Cupola) developed for providers working in the oropharyngeal region.

Results

The mean number of 0.3 μm particles with no Cupola was 3777 (SD: ± 556), with The Cupola was 2068 (SD: ± 1468) and with the Cupola and Drape was 2031 (SD: ± 1108) (p < 0.015). The mean number of 0.5 μm airborne particles with no Cupola was 65 (SD: ± 7), with The Cupola was 29 (SD: ± 28) and with the Cupola and Drape was 28 (SD: ± 23) (p < 0.05). Results showed a significant reduction of aerosols generated during simulated dental procedures when the Cupola was used. The Cupola offers an extra layer of protection in addition to the recommended personal protective equipment.
Transcriptome of Aquilaria malaccensis containing agarwood formed naturally and induced artificially
Authors: Abdul Kadir Farah Adibah , Azizan Kamalrul Azlan , Othman Roohaida
Published: March 2021

Objectives

Agarwood is the aromatic heartwood formed upon wounding of Aquilaria trees either naturally formed due to physical wound sustained from natural phenomena followed by microbial infection, or artificially induced using different inoculation methods. Different induction methods produce agarwoods with different aromas which have impacts on their commercial values. In lieu of elucidating the molecular mechanisms of agarwood formation under different treatment conditions, the transcriptome profiles of trunk tissues from healthy A. malaccensis tree, and naturally and artificially induced trees were obtained.

Data description

The transcriptome of trunk tissues from healthy A. malaccensis, and naturally and artificially induced trees were sequenced using Illumina HiSeq™ 4000 platform which resulted in a total of 38.4 Gb clean reads with Q30 rate of at least 91%. The transcriptome consists of 85,986 unigenes containing 1305 bases on average which were annotated against several databases. From this, 44,654 unigenes were mapped to 290 metabolic pathways in the Kyoto Encyclopedia of Genes and Genomes database. These transcriptome data represent considerable contribution towards Aquilaria transcriptome data and enhance current knowledge in comprehending the molecular mechanisms underlying agarwood formation in Aquilaria spp.
Pre-adolescence DNA methylation is associated with BMI status change from pre- to post-adolescence
Authors: Wang Jiajing , Zhang Hongmei , Rezwan Faisal I. , Relton Caroline , Arshad S. Hasan , Holloway John W.
Published: March 2021

Background

Previous studies have shown that DNA methylation (DNAm) is associated with body mass index (BMI). However, it is unknown whether DNAm at pre-adolescence is associated with BMI status transition from pre- to post-adolescence. In the Isle of Wight (IoW) birth cohort, genome-wide DNA methylation in whole blood was measured using Illumina Infinium Human450 and EPIC BeadChip arrays in n = 325 subjects, and pre- to post-adolescence BMI transition was classified into four groups: (1) normal to normal, (2) normal to overweight or obese, (3) overweight or obese to normal, and (4) persistent overweight or obese. We used recursive random forest to screen genome-wide Cytosine-phosphate-Guanine (CpG) sites with DNAm potentially associated with BMI transition for each gender, and the association of BMI status transition with DNAm at an earlier age was assessed via logistic regressions. To evaluate gender specificity, interactions between DNAm and gender were included in the model. Findings in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC).

Results

In total, 174 candidate CpGs were selected including CpGs from screening and CpGs previously associated correctionally with BMI in children and adults. Of these 174 CpGs, pre-adolescent DNAm of 38 CpGs in the IoW cohort was associated with BMI status transition, including 30 CpGs showing gender-specific associations. Thirteen CpGs showed consistent associations between the IoW cohort and the ALSPAC cohort (11 of which were gender-specific).

Conclusion

Pre-adolescence DNAm is associated with the change in BMI status from pre- to post-adolescence and such associations are likely to be gender-specific.
Plasma neurofilament light and phosphorylated tau 181 as biomarkers of Alzheimer’s disease pathology and clinical disease progression
Authors: Clark Christopher , Lewczuk Piotr , Kornhuber Johannes , Richiardi Jonas , Maréchal Bénédicte , Karikari Thomas K. , Blennow Kaj , Zetterberg Henrik , Popp Julius
Published: March 2021

Background

To assess the performance of plasma neurofilament light (NfL) and phosphorylated tau 181 (p-tau181) to inform about cerebral Alzheimer’s disease (AD) pathology and predict clinical progression in a memory clinic setting.

Methods

Plasma NfL and p-tau181, along with established cerebrospinal fluid (CSF) biomarkers of AD pathology, were measured in participants with normal cognition (CN) and memory clinic patients with cognitive impairment (mild cognitive impairment and dementia, CI). Clinical and neuropsychological assessments were performed at inclusion and follow-up visits at 18 and 36 months. Multivariate analysis assessed associations of plasma NfL and p-tau181 levels with AD, single CSF biomarkers, hippocampal volume, and clinical measures of disease progression.

Results

Plasma NfL levels were higher in CN participants with an AD CSF profile (defined by a CSF p-tau181/Aβ1–42 > 0.0779) as compared with CN non-AD, while p-tau181 plasma levels were higher in CI patients with AD. Plasma NfL levels correlated with CSF tau and p-tau181 in CN, and with CSF tau in CI patients. Plasma p-tau181 correlated with CSF p-tau181 in CN and with CSF tau, p-tau181, Aβ1–42, and Aβ1–42/Aβ1–40 in CI participants. Compared with a reference model, adding plasma p-tau181 improved the prediction of AD in CI patients while adding NfL did not. Adding p-tau181, but not NfL levels, to a reference model improved prediction of cognitive decline in CI participants.

Conclusion

Plasma NfL indicates neurodegeneration while plasma p-tau181 levels can serve as a biomarker of cerebral AD pathology and cognitive decline. Their predictive performance depends on the presence of cognitive impairment.
Distinct tooth regeneration systems deploy a conserved battery of genes
Authors: Square Tyler A. , Sundaram Shivani , Mackey Emma J. , Miller Craig T.
Published: March 2021

Background

Vertebrate teeth exhibit a wide range of regenerative systems. Many species, including most mammals, reptiles, and amphibians, form replacement teeth at a histologically distinct location called the successional dental lamina, while other species do not employ such a system. Notably, a ‘lamina-less’ tooth replacement condition is found in a paraphyletic array of ray-finned fishes, such as stickleback, trout, cod, medaka, and bichir. Furthermore, the position, renewal potential, and latency times appear to vary drastically across different vertebrate tooth regeneration systems. The progenitor cells underlying tooth regeneration thus present highly divergent arrangements and potentials. Given the spectrum of regeneration systems present in vertebrates, it is unclear if morphologically divergent tooth regeneration systems deploy an overlapping battery of genes in their naïve dental tissues.

Results

In the present work, we aimed to determine whether or not tooth progenitor epithelia could be composed of a conserved cell type between vertebrate dentitions with divergent regeneration systems. To address this question, we compared the pharyngeal tooth regeneration processes in two ray-finned fishes: zebrafish (Danio rerio) and threespine stickleback (Gasterosteus aculeatus). These two teleost species diverged approximately 250 million years ago and demonstrate some stark differences in dental morphology and regeneration. Here, we find that the naïve successional dental lamina in zebrafish expresses a battery of nine genes (bmpr1aa, bmp6, cd34, gli1, igfbp5a, lgr4, lgr6, nfatc1,andpitx2), while active Wnt signaling andLef1expression occur during early morphogenesis stages of tooth development. We also find that, despite the absence of a histologically distinct successional dental lamina in stickleback tooth fields, the same battery of nine genes (Bmpr1a,Bmp6,CD34,Gli1,Igfbp5a,Lgr4,Lgr6,Nfatc1, andPitx2) are expressed in the basalmost endodermal cell layer, which is the region most closely associated with replacement tooth germs. Like zebrafish, stickleback replacement tooth germs additionally expressLef1and exhibit active Wnt signaling. Thus, two fish systems that either have an organized successional dental lamina (zebrafish) or lack a morphologically distinct successional dental lamina (sticklebacks) deploy similar genetic programs during tooth regeneration.

Conclusions

We propose that the expression domains described here delineate a highly conserved “successional dental epithelium” (SDE). Furthermore, a set of orthologous genes is known to mark hair follicle epithelial stem cells in mice, suggesting that regenerative systems in other epithelial appendages may utilize a related epithelial progenitor cell type, despite the highly derived nature of the resulting functional organs.
Spontaneous primary pneumomediastinum: is it always benign?
Authors: Alemu Berhanu N. , Yeheyis Ephraim T. , Tiruneh Abraham G.
Published: March 2021

Background

Spontaneous Pneumomediastinum is a rare disease. It could be a simple and self-limited condition or be a life-threatening complication of underlying diseases. The therapeutic options also differ by the cause. This systematic review was done to provide, as far as we know, the first attempt to broadly assess the clinical feature, predisposing factors, possible management, and outcome of spontaneous primary pneumomediastinum.

Methods

In addition to the two patients treated at our hospital, a Pub Med Search for literature on case reports of spontaneous pneumomediastinum published in English up to November 2018 was done. We extracted data on patients' demographic characteristics, symptoms, timing, diagnosis, management, and outcome of the treatment were analyzed based on the preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA)

Result

A total of 339 cases were reviewed. 71.7% of them were male. The Mean age affected was 22.4 ± 11.3 years. Chest pain, 196 (57.8%), is the most common presenting symptom, followed by dyspnea, 156 (46%), cough 95 (28%), neck swelling 92 (27.13%), cervical pain 88 (25.9%), dysphagia 39 (11.5%), odynophagia 37 (10.9%), and Dysphonia 14 (4.1%). Fifty-seven patients (16.8%) had a prior history of Asthma, 19 (5.6%) had Connective Tissue Disorders, and 12 (3.5%) had associated malignancy as an identified risk factor. In 35 (10.3%) patients, spontaneous pneumomediastinum was found incidentally. The mean number of days before the clinical resolution of spontaneous pneumomediastinum was 6.65 ± 11.8 days and the average hospital stay was 4.15 ± 1.93 days. Nineteen (5.6%) patients have died as a result of the underlying disease not related to SPM.

Conclusion

Spontaneous pneumomediastinum is uncommon, usually benign, a self-limited disorder that commonly occurs in a young adult without any apparent precipitating factor or disease. Spontaneous pneumomediastinum usually responds very well to conservative treatment without recurrence. However, secondary causes should be ruled out to minimize the unfavorable outcome.
SMPLIP-Score: predicting ligand binding affinity from simple and interpretable on-the-fly interaction fingerprint pattern descriptors
Authors: Kumar Surendra , Kim Mi-hyun
Published: March 2021

In drug discovery, rapid and accurate prediction of protein–ligand binding affinities is a pivotal task for lead optimization with acceptable on-target potency as well as pharmacological efficacy. Furthermore, researchers hope for a high correlation between docking score and pose with key interactive residues, although scoring functions as free energy surrogates of protein–ligand complexes have failed to provide collinearity. Recently, various machine learning or deep learning methods have been proposed to overcome the drawbacks of scoring functions. Despite being highly accurate, their featurization process is complex and the meaning of the embedded features cannot directly be interpreted by human recognition without an additional feature analysis. Here, we propose SMPLIP-Score (Substructural Molecular and Protein–Ligand Interaction Pattern Score), a direct interpretable predictor of absolute binding affinity. Our simple featurization embeds the interaction fingerprint pattern on the ligand-binding site environment and molecular fragments of ligands into an input vectorized matrix for learning layers (random forest or deep neural network). Despite their less complex features than other state-of-the-art models, SMPLIP-Score achieved comparable performance, a Pearson’s correlation coefficient up to 0.80, and a root mean square error up to 1.18 in pKunits with several benchmark datasets (PDBbind v.2015, Astex Diverse Set, CSAR NRC HiQ, FEP, PDBbind NMR, and CASF-2016). For this model, generality, predictive power, ranking power, and robustness were examined using direct interpretation of feature matrices for specific targets.
RNAi-mediated silencing of Trichinella spiralis glutaminase results in reduced muscle larval infectivity
Authors: Gao Yuan , Meng Xiaoqing , Yang Xiao , Meng Shi , Han Caixia , Li Xiaoyun , Wang Shuang , Li Wei , Song Mingxin
Published: March 2021

Trichinella spiralis is an important foodborne parasitic nematode distributed worldwide that infects humans and animals. Glutaminase (GLS) is an important gene in the glutamine-dependent acid resistance (AR) system; however, its role in T. spiralis muscle larvae (ML) remains unclear. The present study aimed to characterize T. spiralis GLS (TsGLS) and assess its function in T. spiralis ML AR both in vitro and in vivo using RNA interference. The results indicated that native TsGLS (72 kDa) was recognized by anti-rTsGLS serum at the muscle larvae stage; moreover, an immunofluorescence assay confirmed that TsGLS was located in the epidermis of ML. After silencing the TsGLS gene, the relative expression of TsGLS mRNA and the survival rate of T. spiralis ML were reduced by 60.11% and 16.55%, respectively, compared to those in the PBS and control groups. In vivo AR assays revealed that the worm numbers at 7 and 35 days post-infection (dpi) decreased by 61.64% and 66.71%, respectively, compared to those in the PBS group. The relative expression of TsGLS mRNA in F1 generation T. spiralis ML was reduced by 42.52%, compared to that in the PBS group. To the best of our knowledge, this is the first study to report the presence of the glutamine-dependent AR system in T. spiralis. Our results indicate that TsGLS plays a crucial role in the T. spiralis AR system; thus, it could be used as a potential candidate target molecule for producing vaccines against T. spiralis infection.
Association between clinical respiratory signs, lung lesions detected by thoracic ultrasonography and growth performance in pre‐weaned dairy calves
Authors: Cuevas-Gómez Inmaculada , McGee Mark , Sánchez José María , O’Riordan Edward , Byrne Nicky , McDaneld Tara , Earley Bernadette
Published: March 2021

Background

Bovine respiratory disease (BRD) is the main cause of mortality among 1-to-5 month old calves in Ireland, accounting for approximately one-third of deaths. Despite widespread use of clinical respiratory signs for diagnosing BRD, lung lesions are detected, using thoracic ultrasonography (TUS) or following post-mortem, in calves showing no clinical signs. This highlights the limitation of clinical respiratory signs as a method of detecting sub-clinical BRD. Using 53 purchased artificially-reared male dairy calves, the objectives of this study were to: (i) characterise the BRD incidence detected by clinical respiratory signs and/or TUS, (ii) investigate the association between clinical respiratory signs and lung lesions detected by TUS, and (iii) assess the effect of BRD on pre-weaning growth.

Results

Clinical BRD (based on Wisconsin clinical respiratory score and/or rectal temperature > 39.6 ºC) was detected in 43 % and sonographic changes (lung lesions) were detected in 64 % of calves from purchase (23 (SD; 6.2) days of age) until weaning, 53 days post-arrival. Calves with clinical BRD were treated. Sixty-one per cent calves affected with clinical BRD had lung lesions 10.5 days (median) before detection of clinical signs. Moderate correlations (rsp 0.70; P < 0.05) were found between cough and severe lung lesions on arrival day, and between rectal temperature > 39.6 ºC and lung lesions ≥ 2 cm2 on day 7 (rsp 0.40; P < 0.05) post-arrival. Mean average daily live weight gain (ADG) of calves from purchase to weaning was 0.75 (SD; 0.10) kg; calves with or without clinical BRD did not differ in ADG (P > 0.05), whereas ADG of those with severe lung lesions (lung lobe completely consolidated or pulmonary emphysema) was 0.12 kg/d less (P < 0.05) than calves without lung lesions.

Conclusions

Thoracic ultrasonography detected lung consolidation in calves that did not show signs of respiratory disease. The presence of severe lung lesions was associated with reduced pre-weaning growth. These findings emphasise the importance of using TUS in addition to clinical respiratory scoring of calves for an early and accurate detection of clinical and sub-clinical BRD.
Effects of psychosocial interventions among people cared for in emergency departments after a suicide attempt: a systematic review protocol
Authors: da Silva Ana Paula Coutinho , Henriques Margarida Rangel , Rothes Inês Areal , Zortea Tiago , Santos José Carlos , Cuijpers Pim
Published: March 2021

Background

The care of the emergency department (ED) for a person after a suicide attempt can act as a protector against future suicidal behavior. For this reason, it is essential that the ED ensure an assistance that involves effective interventions in preventing suicidal behaviors. Among suicidal behaviors, it is known that suicide attempt is one of the most lethal risk factors for consummated suicide. In addition, the risk for further attempts is greater in the period from the immediate post-discharge up to 12 months after the last attempt. This makes the ED a key link in the suicide prevention chain. The purpose of this review is to investigate the effects of psychosocial interventions on suicide prevention, when applied in the ED after a suicide attempt.

Methods

This systematic review protocol was built and registered with the collaboration of a multidisciplinary scientific team. The review will include randomized clinical studies, quasi-experimental trials, and comparative observational studies, all conducted with people (11 years old or more) who have received a psychosocial suicide prevention intervention initiated in the ED after a suicide attempt. The research will be conducted across databases such as Cochrane Library, PubMed, EMBASE, PsycINFO, and DARE. The repetition of a suicide attempt and death by suicide as primary outcomes will be analyzed. The eligibility of the studies and data extraction will be carried out by matched and blind researchers. The risk of bias will be addressed using appropriate instruments. The analyses and synthesis of the results will be both qualitative and quantitative.

Discussion

From a public health point of view, suicide is in itself a public health problem and requires appropriate interventions at different levels of care in order to be prevented. Taking into account that a high percentage of people who died by suicide sought the ED for suicide attempt in the year before their death, the ED is a clinical context with a privileged potential to implement these interventions. Presently, several clinical studies seek to validate interventions to be adopted regarding the prevention of suicidal behavior. Current evidence indicates that different interventions must be strategically combined to reduce suicide attempts and their mortality.

Systematic review registration

PROSPERO registration number CRD42019131040
Asymptotic properties of a population model with Allee effects in random environments
Authors: Zheng Famei , Hu Guixin
Published: March 2021

In this research, we probe the influences of two common types of stochastic noises in the environment, namely, white noise and telephone noise, and put forward a stochastic differential equation population model with Allee effects. We analyze some asymptotic behaviors of the model, including extermination, persistence and invariant measure. Some vital functions of white noise and telephone noise on these asymptotic behaviors of the model are discovered and numerically expounded.
Note on norm of an m-linear integral-type operator between weighted-type spaces
Authors: Stević Stevo
Published: March 2021

We find a necessary and sufficient condition for the boundedness of anm-linear integral-type operator between weighted-type spaces of functions, and calculate norm of the operator, complementing some results by L. Grafakos and his collaborators. We also present an inequality which explains a detail in the proof of the boundedness of the linear integral-type operator on$L^{p}({\mathbb {R}}^{n})$Lp(Rn)space.
Shifted Jacobi polynomials for nonlinear singular variable-order time fractional Emden–Fowler equation generated by derivative with non-singular kernel
Authors: Heydari M. H. , Avazzadeh Z. , Atangana A.
Published: March 2021

In this work, a nonlinear singular variable-order fractional Emden–Fowler equation involved with derivative with non-singular kernel (in the Atangana–Baleanu–Caputo type) is introduced and a computational method is proposed for its numerical solution. The desired method is established upon the shifted Jacobi polynomials and their operational matrix of variable-order fractional differentiation (which is extracted in the present study) together with the spectral collocation method. The presented method transforms obtaining the solution of the main problem into obtaining the solution of an algebraic system of equations. Several numerical examples are examined to show the validity and the high accuracy of the established method.
Economic development, social integration, and the subjective well-being of residents in the western regions of China: based on the perspective of multi-ethnic China
Authors: Yang Jianke , Wang Qi
Published: March 2021

Based on a large sample of survey data collected from 12 Chinese provinces, municipalities directly under the central government and autonomous regions in the western regions of China, this article discusses the subjective well-being of the residents of all ethnic groups in the western regions, along the two dimensions of economic development and social integration. The results show that the overall subjective well-being of all ethnic groups in Western China is good, and the percentage of people who indicated that they often feel happy is generally higher than the percentage of those who often feel unhappy. The residents of ethnic minority status such as the Huis and the Uyghurs experience good subjective well-being more often than residents of other ethnic groups. Microscopic indicators, such as the level of household income, and macroscopic indicators, such as the level of regional economic development, can exert significant positive impacts on the subjective well-being of residents from various ethnic groups. In addition, emotional integration, trust-based integration, and integration through communication—as important variables of social identity and social acceptance—can also have significant positive impacts on improving the subjective well-being of residents of all ethnic groups. The article concludes that, for the residents of all ethnic groups living in the less developed western regions of China, economic development and increased income remain the key means of improving the subjective well-being, and promoting inter-ethnic interactions and strengthening social integration are also positive methods of effectively improving the subjective well-being.
Recovery of photoacoustic images based on accurate ultrasound positioning
Authors: Pan Yinhao , Chen Ningbo , Liu Liangjian , Liu Chengbo , Xu Zhiqiang , Zhang Jianhui
Published: March 2021

Photoacoustic microscopy is an in vivo imaging technology based on the photoacoustic effect. It is widely used in various biomedical studies because it can provide high-resolution images while being label-free, safe, and harmless to biological tissue. Polygon-scanning is an effective scanning method in photoacoustic microscopy that can realize fast imaging of biological tissue with a large field of view. However, in polygon-scanning, fluctuations of the rotating motor speed and the geometric error of the rotating mirror cause image distortions, which seriously affect the photoacoustic-microscopy imaging quality. To improve the image quality of photoacoustic microscopy using polygon-scanning, an image correction method is proposed based on accurate ultrasound positioning. In this method, the photoacoustic and ultrasound imaging data of the sample are simultaneously obtained, and the angle information of each mirror used in the polygon-scanning is extracted from the ultrasonic data to correct the photoacoustic images. Experimental results show that the proposed method can significantly reduce image distortions in photoacoustic microscopy, with the image dislocation offset decreasing from 24.774 to 10.365 μm.
Validity and reliability of the revised Arabic language test for 2–4-year-old children: cross-sectional study
Authors: Rifaie Nahla , Hamza Tarek Mohamed Abdel Wahab , Elfiky Yomna Hassan
Published: March 2021

Background

Language assessment in children using subjective and objective tests has been an issue to discuss. The aim of this study is to revise and prove the validity and reliability of the Arabic language test (ALT) for the age range from 2 to 4 years old. New design of the test format and test pictures was performed and tested on a pilot study of 30 normal children with no language problems, 15 in each 1 year age group, within the same age range of the standardization sample. The standardization sample on which the test was then applied was 400 normal Egyptian children in the age range from 2 to 4 years old 200 at 2–3 years old and 200 at 3–4 years old. Retesting was done on 30 children (15 in each group) to prove test-retest reliability, with an interval of 2 weeks. Validity of the test was done using, internal consistency validity, contrasted group validity, factorial validity, face validity, and judgment validity. In the contrasted group validity, a sample of 40 children with delayed language was used.

Results

All validity tests used gave significant scores that proved the high validity of the newly revised test. Also, reliability tests were highly significant.

Conclusion

The newly revised Arabic language test for 2–4 years old is a reliable and valid test to be used to evaluate language development and to detect language deficits among Egyptian children in the same age range.
Evaluation of the efficacy of pirfenidone in progressive chronic hypersensitivity pneumonitis
Authors: Shebl Eman , Hamdy Tarek
Published: March 2021

Background

The present data about the treatment of progressive CHP are few and largely based on observational studies and expert opinion. It is suggested that pirfenidone may slow disease progression in cases of CHP as it has some anti-inflammatory in addition to antifibrotic effects, so this study aimed to evaluate the efficacy of pirfenidone in chronic hypersensitivity pneumonitis. This study included 40 adult patients (≥ 18 years) with a diagnosis of chronic progressive hypersensitivity pneumonitis. The included patients were divided into 2 groups 20 patients in each one.

Group 1 received pirfenidone in addition to the conventional treatment

Group 2 was maintained on conventional treatment.

Forced vital capacity (FVC), 6-min walking test (6MWT), oxygen tension in the arterial blood (PaO2), and St. George’s Respiratory Questionnaire (SGRQ) were measured before and after 6 months of a pirfenidone treatment trial.

Results

The present study showed that in patients with progressive chronic hypersensitivity pneumonitis, adding pirfenidone to their conventional treatment was associated with significantly higher FVC, 6MWT, SaO2, and PaO2, and significant lower SGRQ score compared to patients who were maintained only on their conventional treatment at 6 months after treatment

Conclusion

Pirfenidone can reduce the progression of chronic hypersensitivity pneumonitis and so it can be considered a therapeutic option in its treatment.

Trial registration

ClinicalTrials.gov, NCT04675619.
First report of the invasive snail Pomacea canaliculata in Kenya
Authors: Buddie Alan G. , Rwomushana Ivan , Offord Lisa C. , Kibet Simeon , Makale Fernadis , Djeddour Djamila , Cafa Giovanni , Vincent Koskei K. , Muvea Alexander M. , Chacha Duncan , Day Roger K.
Published: March 2021

Following reports of an invasive snail causing crop damage in the expansive Mwea irrigation scheme in Kenya, samples of snails and associated egg masses were collected and sent to CABI laboratories in the UK for molecular identification. DNA barcoding analyses using the cytochrome oxidase subunit I gene gave preliminary identification of the snails as Pomacea canaliculata, widely considered to have the potential to be one of the most invasive invertebrates of waterways and irrigation systems worldwide and which is already causing issues throughout much of south-east Asia. To the best of our knowledge, this is the first documented record of P. canaliculata in Kenya, and the first confirmed record of an established population in continental Africa. This timely identification shows the benefit of molecular identification and the need for robust species identifications: even a curated sequence database such as that provided by the Barcoding of Life Data system may require additional checks on the veracity of the underlying identifications. We found that the egg mass tested gave an identical barcode sequence to the adult snails, allowing identifications to be made more rapidly. Part of the nuclear elongation factor 1 alpha gene was sequenced to confirm that the snail was P. canaliculata and not a P. canaliculata/P. maculata interspecies hybrid. Given the impact of this species in Asia, there is need for an assessment of the risk to Africa, and the implementation of an appropriate response in Kenya and elsewhere to manage this new threat to agriculture and the environment.
Eulerian partial-differential-equation methods for complex-valued eikonals in attenuating media
Authors: Hu Jiangtao , Qian Jianliang , Song Jian , Ouyang Min , Cao Junxing , Leung Shingyu
Published: March 2021

Seismic waves in earth media usually undergo attenuation, causing energy losses and phase distortions. In the regime of high-frequency asymptotics, a complex-valued eikonal is an essential ingredient for describing wave propagation in attenuating media, where the real and imaginary parts of the eikonal function capture dispersion effects and amplitude attenuation of seismic waves, respectively. Conventionally, such a complex-valued eikonal is mainly computed either by tracing rays exactly in complex space or by tracing rays approximately in real space so that the resulting eikonal is distributed irregularly in real space. However, seismic data processing methods, such as prestack depth migration and tomography, usually require uniformly distributed complex-valued eikonals. Therefore, we have developed a unified framework to Eulerianize several popular approximate real-space ray-tracing methods for complex-valued eikonals so that the real and imaginary parts of the eikonal function satisfy the classic real-space eikonal equation and a novel real-space advection equation, respectively, and we dub the resulting method the Eulerian partial-differential-equation method. We further develop highly efficient high-order methods to solve these two equations by using the factorization idea and the Lax-Friedrichs weighted essentially nonoscillatory schemes. Numerical examples demonstrate that our method yields highly accurate complex-valued eikonals, analogous to those from ray-tracing methods. Our methods can be useful for migration and tomography in attenuating media.
Correlations between the static and anisotropic dynamic elastic properties of lacustrine shales under triaxial stress: Examples from the Ordos Basin, China
Authors: Han Tongcheng , Yu Hongyan , Fu Li-Yun
Published: March 2021

Shales are abundant and are increasingly important for the hydrocarbon industry as source rocks and unconventional reservoirs. The anisotropic dynamic elastic properties of shales are important in the exploration stage of shale reservoirs whereas their static elastic properties are key for the hydraulic fracturing for the more efficient development of shale gas and oil. However, the correlations between the static and anisotropic dynamic elastic properties that could provide a basis for the seismic methods to potentially evaluate the fracturing ability of shales without the need of cored samples from the borehole are still poorly understood. We have demonstrated, through dedicated simultaneous laboratory measurements of the anisotropic velocities and the strains of samples under triaxial stress, how the static and anisotropic dynamic elastic properties are correlated in seven lacustrine shales from the Ordos Basin, one of the major shale gas plays in China. The results show that the static and anisotropic dynamic elastic properties are stress-dependent. More importantly, the anisotropic velocities are found to be approximately linearly correlated with the axial strains of the samples at differential stress (the difference between axial stress and confining stress) greater than 30 MPa, with the slopes of the linear correlations in excellent linear relationship with Young’s moduli determined from the static elastic measurements. The results not only reveal the internal link between the static and anisotropic dynamic elastic properties of lacustrine shales, but they also pave a potential way for the anisotropic seismic explorations to remotely evaluate the fracturing ability of shales.
Risk Prediction Using Bayesian Networks: An Immunotherapy Case Study in Patients With Metastatic Renal Cell Carcinoma
Authors: Gupta Alind , Arora Paul , Brenner Darren , Vanderpuye-Orgle Jacqueline , Boyne Devon J. , Edmondson-Jones Mark , Parkhomenko Elena , Stevens Warren , Dudani Shaan , Heng Daniel Y. C. , Wagner Samuel , Borrill John , Wu Elise
Published: March 2021

PURPOSE

To address the need for more accurate risk stratification models for cancer immuno-oncology, this study aimed to develop a machine-learned Bayesian network model (BNM) for predicting outcomes in patients with metastatic renal cell carcinoma (mRCC) being treated with immunotherapy.

METHODS

Patient-level data from the randomized, phase III CheckMate 025 clinical trial comparing nivolumab with everolimus for second-line treatment in patients with mRCC were used to develop the BNM. Outcomes of interest were overall survival (OS), all-cause adverse events, and treatment-related adverse events (TRAE) over 36 months after treatment initiation. External validation of the model's predictions for OS was conducted using data from select centers from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

RESULTS

Areas under the receiver operating characteristic curve (AUCs) for BNM-based classification of OS using baseline data were 0.74, 0.71, and 0.68 over months 12, 24, and 36, respectively. AUC for OS at 12 months increased to 0.86 when treatment response and progression status in year 1 were included as predictors; progression and response at 12 months were highly prognostic of all outcomes over the 36-month period. AUCs for adverse events and treatment-related adverse events were approximately 0.6 at 12 months but increased to approximately 0.7 by 36 months. Sensitivity analysis comparing the BNM with machine learning classifiers showed comparable performance. Test AUC on IMDC data for 12-month OS was 0.71 despite several variable imbalances. Notably, the BNM outperformed the IMDC risk score alone.

CONCLUSION

The validated BNM performed well at prediction using baseline data, particularly with the inclusion of response and progression at 12 months. Additionally, the results suggest that 12 months of follow-up data alone may be sufficient to inform long-term survival projections in patients with mRCC.
HER2 Expression, Test Deviations, and Their Impact on Survival in Metastatic Gastric Cancer: Results From the Prospective Multicenter VARIANZ Study
Authors: Haffner Ivonne , Schierle Katrin , Raimúndez Elba , Geier Birgitta , Maier Dieter , Hasenauer Jan , Luber Birgit , Walch Axel , Kolbe Katharina , Riera Knorrenschild Jorge , Kretzschmar Albrecht , Rau Beate , Fischer von Weikersthal Ludwig , Ahlborn Miriam , Siegler Gabriele , Fuxius Stefan , Decker Thomas , Wittekind Christian , Lordick Florian
Published: March 2021

PURPOSE

Trastuzumab is the only approved targeted drug for first-line treatment of human epidermal growth factor receptor 2–positive (HER2+) metastatic gastric cancer (mGC). However, not all patients respond and most eventually progress. The multicenter VARIANZ study aimed to investigate the background of response and resistance to trastuzumab in mGC.

METHODS

Patients receiving medical treatment for mGC were prospectively recruited in 35 German sites and followed for up to 48 months. HER2 status was assessed centrally by immunohistochemistry and chromogenic in situ hybridization. In addition, HER2 gene expression was assessed using qPCR.

RESULTS

Five hundred forty-eight patients were enrolled, and 77 had HER2+ mGC by central assessment (14.1%). A high deviation rate of 22.7% between central and local test results was seen. Patients who received trastuzumab for centrally confirmed HER2+ mGC (central HER2+/local HER2+) lived significantly longer as compared with patients who received trastuzumab for local HER2+ but central HER2− mGC (20.5 months, n = 60 v 10.9 months, n = 65; hazard ratio, 0.42; 95% CI, 8.2 to 14.4; P < .001). In the centrally confirmed cohort, significantly more tumor cells stained HER2+ than in the unconfirmed cohort, and the HER2 amplification ratio was significantly higher. A minimum of 40% HER2+ tumor cells and a HER2 amplification ratio of ≥ 3.0 were calculated as optimized thresholds for predicting benefit from trastuzumab.

CONCLUSION

Significant discrepancies in HER2 assessment of mGC were found in tumor specimens with intermediate HER2 expression. Borderline HER2 positivity and heterogeneity of HER2 expression should be considered as resistance factors for HER2-targeting treatment of mGC. HER2 thresholds should be reconsidered. Detailed reports with quantification of HER2 expression and amplification levels may improve selection of patients for HER2-directed treatment.
Towards a kinetic theory of dark-soliton gases in one-dimensional superfluids
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Authors: Pereira C. , Mendonça J. T. , Rodrigues J. D. , Terças H.
Published: March 2021

Soliton hydrodynamics is an appealing tool to describe strong turbulence in low-dimensional systems. Strong turbulence in quasi-one-dimensional superfluids, such as Bose-Einstein condensates, involves the dynamics of dark solitons and, therefore, the description of a statistical ensemble of dark solitons, i.e., soliton gases, is necessary. In this work, we propose a phase-space (kinetic) description of dark-soliton gases, introducing a kinetic equation that is formally similar to the Vlasov equation in plasma physics. We show that the proposed kinetic theory can capture the dynamical features of soliton gases and show that it sustains an acoustic mode, a fact that we corroborate with the help of direct numerical simulations. Our findings motivate the investigation of the microscopic structure of out-of-equilibrium and turbulent regimes in low-dimensional superfluids.
BCAA Supplementation in Mice with Diet-induced Obesity Alters the Metabolome Without Impairing Glucose Homeostasis
Authors: Lee Jennifer , Vijayakumar Archana , White Phillip J , Xu Yuping , Ilkayeva Olga , Lynch Christopher J , Newgard Christopher B , Kahn Barbara B
Published: March 2021

Circulating branched chain amino acid (BCAA) levels are elevated in obese humans and genetically obese rodents. However, the relationship of BCAAs to insulin resistance in diet-induced obese mice, a commonly used model to study glucose homeostasis, is still ill-defined. Here we examined how high-fat high-sucrose (HFHS) or high-fat diet (HFD) feeding, with or without BCAA supplementation in water, alters the metabolome in serum/plasma and tissues in mice and whether raising circulating BCAA levels worsens insulin resistance and glucose intolerance. Neither HFHS nor HFD feeding raised circulating BCAA levels in insulin-resistant diet-induced obese mice. BCAA supplementation raised circulating BCAA and branched-chain α-keto acid levels and C5-OH/C3-DC acylcarnitines (AC) in muscle from mice fed an HFHS diet or HFD, but did not worsen insulin resistance. A set of short- and long-chain acyl CoAs were elevated by diet alone in muscle, liver, and white adipose tissue (WAT), but not increased further by BCAA supplementation. HFD feeding reduced valine and leucine oxidation in WAT but not in muscle. BCAA supplementation markedly increased valine oxidation in muscle from HFD-fed mice, while leucine oxidation was unaffected by diet or BCAA treatment. Here we establish an extensive metabolome database showing tissue-specific changes in mice on 2 different HFDs, with or without BCAA supplementation. We conclude that mildly elevating circulating BCAAs and a subset of ACs by BCAA supplementation does not worsen insulin resistance or glucose tolerance in mice. This work highlights major differences in the effects of BCAAs on glucose homeostasis in diet-induced obese mice versus data reported in obese rats and in humans.
The SRCAP chromatin remodeling complex promotes oxidative metabolism during prenatal heart development
Authors: Xu Mingjie , Yao Jie , Shi Yingchao , Yi Huijuan , Zhao Wukui , Lin Xinhua , Yang Zhongzhou
Published: March 2021

Mammalian heart development relies on cardiomyocyte mitochondrial maturation and metabolism. Embryonic cardiomyocytes make a metabolic shift from anaerobic glycolysis to oxidative metabolism by mid-gestation. VHL-HIF signaling favors anaerobic glycolysis but this process subsides by E14.5. Meanwhile, oxidative metabolism becomes activated but its regulation is largely elusive. Here, we first pinpointed a crucial temporal window for mitochondrial maturation and metabolic shift, and uncovered the pivotal role of the SRCAP chromatin remodeling complex in these processes in mouse. Disruption of this complex massively suppressed the transcription of key genes required for the tricarboxylic acid cycle, fatty acid β-oxidation and ubiquinone biosynthesis, and destroyed respirasome stability. Furthermore, we found that the SRCAP complex functioned through H2A.Z deposition to activate transcription of metabolic genes. These findings have unveiled the important physiological functions of the SRCAP complex in regulating mitochondrial maturation and promoting oxidative metabolism during heart development, and shed new light on the transcriptional regulation of ubiquinone biosynthesis.
How Does Firm Scope Depend on Customer Switching Costs? Evidence from Mobile Telecommunications Markets
Authors: Abolfathi Niloofar , Santamaria Simone , Williams Charles
Published: March 2021

This paper examines the relative advantages of single-product and multiproduct firms following changes in customer switching costs. Whereas a single-product firm can closely tailor offerings to customers’ needs, a multiproduct firm can create value for customers in the form of flexibility, allowing them to change between product varieties as preferences evolve without needing to switch providers. We argue that this value-creation mechanism is more effective when customers face high switching costs and explore this prediction in the mobile telecommunications sector, using an exogenous policy change (mobile number portability) that suddenly decreases customer switching costs. Our results reveal that when customer switching costs fall, multiproduct firms see lower growth than single-product firms, and entry with a multiproduct offering becomes less frequent than before. The study highlights how customer switching costs can enable or inhibit choices of firm scope.

This paper was accepted by Joshua Gans, business strategy.
Understanding dystocia in the field: part 1
Authors: Gormley Rory
Published: March 2021

Difficult births (dystocias) are not uncommon for horses and present significant risks to mare and foal, with potentially fatal consequences. A sound understanding of the normal physiological processes before and during parturition are essential to enable vets to quickly identify when these processes deviate from the norm. To rapidly diagnose the cause of the dystocia, the attending obstetrician should be assured in their approach; resolute in their decision making; and prompt in action if the risks of mare and foal morbidity and mortality are to be managed. Constructive communication with the mare's owners is essential to allow adequate planning to prioritise the outcome. The future fertility of the mare is imperative in many cases yet is often overlooked. The obstetrician must be dynamic and be prepared to alter their approach when necessary. This review outlines the causes of dystocia and the recommended approaches to resolution.
The politics of glocalised post-traumatic emotion worlds and the limits of Cambodian therapeutic subjectivity
Authors: Kidron Carol A.
Published: March 2021

This article traces the way in which a local Cambodian NGO disseminates psychological therapeutic discourse and practice in post-genocide Cambodia potentially laying the constitutive ground for a Cambodian therapeutic subject. Ethnographic interviews with Cambodian interlocutors allow for an examination of Cambodian perceptions of newly disseminated Euro-Western (EW) therapeutic practices and an evaluation of the potential friction between Buddhist Khmer ethnopsychological emotional styles and EW therapeutic emotional styles. Findings point to diverse mechanisms circulating therapeutic subjectivity including rural psychological pedagogy, testimony therapy and a hybrid local-global trauma construct – baksbat-trauma. Baksbat (broken courage)-trauma syncretises Cambodian ethnopsychological and EW psychological understandings of fear, emotional distress and healing. Ethnographic lay Cambodian accounts present cultural friction between the EW therapeutic model and the Cambodian Buddhist/ethnopsychological model. Tacit Cambodian emotional styles include Buddhist avoidance of and resistance to EW emotional working through of and therapeutic talk about past suffering and public memory work. Compared with EW trauma-related fear, the semantic fields of baksbat cannot be disentangled from political and economic structural violence perceived as the root cause of distress nor from Buddhist acceptance and avoidance as a pragmatic and adaptive response. Implications are considered regarding the politicising and depoliticising potential of therapeutic practice and the globalisation of therapeutic subjectivity.