bluuebunny/crossref_metadata_2025 huggingface dataset:
A non-reflecting wave equation through directional wave-field suppression and its finite difference implementation
Authors: Schaeken Teun , Hoogerbrugge Leo , Verschuur Eric
Published: January 2022

The acoustic wave equation describes wave propagation directly from basic physical laws, even in heterogeneous acoustic media. When numerically simulating waves with the wave equation, contrasts in the medium parameters automatically generate all scattering effects. For some applications - such as propagation analysis or certain wave-equation based imaging techniques - it is desirable to suppress these reflections, as we are only interested in the transmitted wave-field. To achieve this, a modification to the constitutive relations is proposed, yielding an extra term that suppresses waves with reference to a preferred direction. The scale-factor $$\alpha$$
α
of this extra term can either be interpreted as a penetration depth or as a typical decay time. This modified theory is implemented using a staggered-grid, time-domain finite difference scheme, where the acoustic Poynting-vector is used to estimate the local propagation direction of the wave-field. The method was successfully used to suppress reflections in media with bone tissue (medical ultrasound) and geophysical subsurface structures, while introducing only minor perturbations to the transmitted wave-field and a small increase in computation time.
Developing a prediction model to estimate the true burden of respiratory syncytial virus (RSV) in hospitalised children in Western Australia
Authors: Gebremedhin Amanuel Tesfay , Hogan Alexandra B. , Blyth Christopher C. , Glass Kathryn , Moore Hannah C.
Published: January 2022

Respiratory syncytial virus (RSV) is a leading cause of childhood morbidity, however there is no systematic testing in children hospitalised with respiratory symptoms. Therefore, current RSV incidence likely underestimates the true burden. We used probabilistically linked perinatal, hospital, and laboratory records of 321,825 children born in Western Australia (WA), 2000–2012. We generated a predictive model for RSV positivity in hospitalised children aged < 5 years. We applied the model to all hospitalisations in our population-based cohort to determine the true RSV incidence, and under-ascertainment fraction. The model’s predictive performance was determined using cross-validated area under the receiver operating characteristic (AUROC) curve. From 321,825 hospitalisations, 37,784 were tested for RSV (22.8% positive). Predictors of RSV positivity included younger admission age, male sex, non-Aboriginal ethnicity, a diagnosis of bronchiolitis and longer hospital stay. Our model showed good predictive accuracy (AUROC: 0.87). The respective sensitivity, specificity, positive predictive value and negative predictive values were 58.4%, 92.2%, 68.6% and 88.3%. The predicted incidence rates of hospitalised RSV for children aged < 3 months was 43.7/1000 child-years (95% CI 42.1–45.4) compared with 31.7/1000 child-years (95% CI 30.3–33.1) from laboratory-confirmed RSV admissions. Findings from our study suggest that the true burden of RSV may be 30–57% higher than current estimates.
Fractional model of MHD blood flow in a cylindrical tube containing magnetic particles
Authors: Majeed Samina , Ali Farhad , Imtiaz Anees , Khan Ilyas , Andualem Mulugeta
Published: January 2022

In recent years, the use of magnetic particles for biomedicine and clinical therapies has gained considerable attention. Unique features of magnetic particles have made it possible to apply them in medical techniques. These techniques not only provide minimal invasive diagnostic tools but also transport medicine within the cell. In recent years, MRI, drug supply to infected tissue, Hyperthermia are more enhanced by the use of magnetic particles. The present study aims to observe heat and mass transport through blood flow containing magnetic particles in a cylindrical tube. Furthermore, the magnetic field is applied vertically to blood flow direction. The Caputo time fractional derivative is used to model the problem. The obtained partial fractional derivatives are solved using Laplace transform and finite Hankel transform. Furthermore, the effect of various physical parameters of our interest has also been observed through various graphs. It has been noticed that the motion of blood and magnetic particles is decelerated when the particle mass parameter and the magnetic parameter are increased. These findings are important for medicine delivery and blood pressure regulation.
Analysis of the cells isolated from epithelial cell rests of Malassez through single-cell limiting dilution
Authors: Islam Syed Taufiqul , Kurashige Yoshihito , Minowa Erika , Yoshida Koki , Paudel Durga , Uehara Osamu , Okada Yunosuke , Bolortsetseg Dembereldorj , Sakakibara Sayaka , Abiko Yoshihiro , Saitoh Masato
Published: January 2022

The epithelial cell rests of Malassez (ERM) are essential in preventing ankylosis between the alveolar bone and the tooth (dentoalveolar ankylosis). Despite extensive research, the mechanism by which ERM cells suppress ankylosis remains uncertain; perhaps its varied population is to reason. Therefore, in this study, eighteen unique clones of ERM (CRUDE) were isolated using the single-cell limiting dilution and designated as ERM 1–18. qRT-PCR, ELISA, and western blot analyses revealed that ERM-2 and -3 had the highest and lowest amelogenin expression, respectively. Mineralization of human periodontal ligament fibroblasts (HPDLF) was reduced in vitro co-culture with CRUDE ERM, ERM-2, and -3 cells, but recovered when an anti-amelogenin antibody was introduced. Transplanted rat molars grown in ERM-2 cell supernatants produced substantially less bone than those cultured in other cell supernatants; inhibition was rescued when an anti-amelogenin antibody was added to the supernatants. Anti-Osterix antibody staining was used to confirm the development of new bones. In addition, next-generation sequencing (NGS) data were analysed to discover genes related to the distinct roles of CRUDE ERM, ERM-2, and ERM-3. According to this study, amelogenin produced by ERM cells helps to prevent dentoalveolar ankylosis and maintain periodontal ligament (PDL) space, depending on their clonal diversity.
Effects of isometric leg training on ambulatory blood pressure and morning blood pressure surge in young normotensive men and women
Authors: Baross Anthony W. , Brook Robert D. , Kay Anthony D. , Howden Reuben , Gaillard Ebony C. , Gordon Ben D. H. , Milne Kevin J. , McGowan Cheri L. M. , Swaine Ian L.
Published: January 2022

Despite the reported association between diurnal variations in ambulatory blood pressure (BP) and elevated cardiovascular disease risk, little is known regarding the effects of isometric resistance training (IRT), a practical BP-lowering intervention, on ambulatory BP and morning BP surge (MBPS). Thus, we investigated whether (i) IRT causes reductions in ambulatory BP and MBPS, in young normotensives, and (ii) if there are any sex differences in these changes. Twenty normotensive individuals (mean 24-h SBP = 121 ± 7, DBP = 67 ± 6 mmHg) undertook 10-weeks of bilateral-leg IRT (4 × 2-min/2-min rest, at 20% maximum voluntary contraction (MVC) 3 days/week). Ambulatory BP and MBPS (mean systolic BP (SBP) 2 h after waking minus the lowest sleeping 1 h mean SBP) was measures pre- and post-training. There were significant reductions in 24-h ambulatory SBP in men (− 4 ± 2 mmHg,P = 0.0001) and women (− 4 ± 2 mmHg,P = 0.0001) following IRT. Significant reductions were also observed in MBPS (− 6 ± 8 mmHg,p = 0.044; − 6 ± 7 mmHg,P = 0.019), yet there were no significant differences between men and women in these changes, and 24-h ambulatory diastolic BP remained unchanged. Furthermore, a significant correlation was identified between the magnitude of the change in MBPS and the magnitude of changes in the mean 2-h SBP after waking for both men and women (men, r = 0.89,P = 0.001; women, r = 0.74,P = 0.014). These findings add further support to the idea that IRT, as practical lifestyle intervention, is effective in significantly lowering ambulatory SBP and MBPS and might reduce the incidence of adverse cardiovascular events that often occur in the morning.
GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence
Authors: Uceda-Castro Rebeca , van Asperen Jessy V. , Vennin Claire , Sluijs Jacqueline A. , van Bodegraven Emma J. , Margarido Andreia S. , Robe Pierre A. J. , van Rheenen Jacco , Hol Elly M.
Published: January 2022

Glioma is the most common form of malignant primary brain tumours in adults. Their highly invasive nature makes the disease incurable to date, emphasizing the importance of better understanding the mechanisms driving glioma invasion. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is characteristic for astrocyte- and neural stem cell-derived gliomas. Glioma malignancy is associated with changes in GFAP alternative splicing, as the canonical isoform GFAPα is downregulated in higher-grade tumours, leading to increased dominance of the GFAPδ isoform in the network. In this study, we used intravital imaging and an ex vivo brain slice invasion model. We show that the GFAPδ and GFAPα isoforms differentially regulate the tumour dynamics of glioma cells. Depletion of either isoform increases the migratory capacity of glioma cells. Remarkably, GFAPδ-depleted cells migrate randomly through the brain tissue, whereas GFAPα-depleted cells show a directionally persistent invasion into the brain parenchyma. This study shows that distinct compositions of the GFAPnetwork lead to specific migratory dynamics and behaviours of gliomas.
Training associated alterations in equine respiratory immunity using a multiomics comparative approach
Authors: Karagianni Anna E. , Kurian Dominic , Cillán-Garcia Eugenio , Eaton Samantha L. , Wishart Thomas M. , Pirie R. Scott
Published: January 2022

Neutrophilic airway inflammation is highly prevalent in racehorses in training, with the term mild to moderate equine asthma (MMEA) being applied to the majority of such cases. Our proposed study is largely derived from the strong association between MMEA in racehorses and their entry into a race training program. The objectives of this study are to characterise the effect of training on the local pulmonary immune system by defining the gene and protein expression of tracheal wash (TW) derived samples from Thoroughbred racehorses prior to and following commencement of race training. Multiomics analysis detected 2138 differentially expressed genes and 260 proteins during the training period. Gene and protein sets were enriched for biological processes related to acute phase response, oxidative stress, haemopoietic processes, as well as to immune response and inflammation. This study demonstrated TW samples to represent a rich source of airway cells, protein and RNA to study airway immunity in the horse and highlighted the benefits of a multiomics methodological approach to studying the dynamics of equine airway immunity. Findings likely reflect the known associations between race-training and both airway inflammation and bleeding, offering further insight into the potential mechanisms which underpin training associated airway inflammation.
A new method for birch tar making with materials available in the Stone Age
Authors: Koch Tabea J. , Schmidt Patrick
Published: January 2022

The use of birch tar can be traced back to the European Middle Palaeolithic and is relevant for our understanding of the technical skills and cognitive abilities of Neanderthals. Due to the lack of archaeological evidence, it remains unknown what techniques were used for birch tar making. Efficiency was recently used as a proxy to determine the method most likely used in the Middle Palaeolithic. Todtenhaupt et al. have proposed a technique employing a groove-like structure that is comparable with the recently presented condensation method. The groove method resulted in higher tar yields compared to other experimental aceramic production processes. However, the implications for Palaeolithic tar making remain unclear because some of the materials used in the experiment were not available then (polished granite slabs). To approach this problem, we replicated the groove with river cobbles and, in a second experiment with flint fragments, to evaluate whether similar results can be obtained. We were successful in producing birch tar in multiple runs with the cobble- and flint-grooves, which, in addition, proved to be more efficient than the condensation method in terms of tar yield per bark input. Our experimental study provides an additional possibility to make prehistoric birch tar.
Accuracy of mutational signature software on correlated signatures
Authors: Wu Yang , Chua Ellora Hui Zhen , Ng Alvin Wei Tian , Boot Arnoud , Rozen Steven G.
Published: January 2022

Mutational signatures are characteristic patterns of mutations generated by exogenous mutagens or by endogenous mutational processes. Mutational signatures are important for research into DNA damage and repair, aging, cancer biology, genetic toxicology, and epidemiology. Unsupervised learning can infer mutational signatures from the somatic mutations in large numbers of tumors, and separating correlated signatures is a notable challenge for this task. To investigate which methods can best meet this challenge, we assessed 18 computational methods for inferring mutational signatures on 20 synthetic data sets that incorporated varying degrees of correlated activity of two common mutational signatures. Performance varied widely, and four methods noticeably outperformed the others: hdp (based on hierarchical Dirichlet processes), SigProExtractor (based on multiple non-negative matrix factorizations over resampled data), TCSM (based on an approach used in document topic analysis), and mutSpec.NMF (also based on non-negative matrix factorization). The results underscored the complexities of mutational signature extraction, including the importance and difficulty of determining the correct number of signatures and the importance of hyperparameters. Our findings indicate directions for improvement of the software and show a need for care when interpreting results from any of these methods, including the need for assessing sensitivity of the results to input parameters.
Region-specific complexity of the intracranial EEG in the sleeping human brain
Authors: Olejarczyk Elzbieta , Gotman Jean , Frauscher Birgit
Published: January 2022

As the brain is a complex system with occurrence of self-similarity at different levels, a dedicated analysis of the complexity of brain signals is of interest to elucidate the functional role of various brain regions across the various stages of vigilance. We exploited intracranial electroencephalogram data from 38 cortical regions using the Higuchi fractal dimension (HFD) as measure to assess brain complexity, on a dataset of 1772 electrode locations. HFD values depended on sleep stage and topography. HFD increased with higher levels of vigilance, being highest during wakefulness in the frontal lobe. HFD did not change from wake to stage N2 in temporo-occipital regions. The transverse temporal gyrus was the only area in which the HFD did not differ between any two vigilance stages. Interestingly, HFD of wakefulness and stage R were different mainly in the precentral gyrus, possibly reflecting motor inhibition in stage R. The fusiform and parahippocampal gyri were the only areas showing no difference between wakefulness and N2. Stages R and N2 were similar only for the postcentral gyrus. Topographical analysis of brain complexity revealed that sleep stages are clearly differentiated in fronto-central brain regions, but that temporo-occipital regions sleep differently.
Dryland irrigation increases accumulation rates of pedogenic carbonate and releases soil abiotic CO2
Authors: Ortiz Anna C. , Jin Lixin , Ogrinc Nives , Kaye Jason , Krajnc Bor , Ma Lin
Published: January 2022

Agricultural fields in drylands are challenged globally by limited freshwater resources for irrigation and also by elevated soil salinity and sodicity. It is well known that pedogenic carbonate is less soluble than evaporate salts and commonly forms in natural drylands. However, few studies have evaluated how irrigation loads dissolved calcium and bicarbonate to agricultural fields, accelerating formation rates of secondary calcite and simultaneously releasing abiotic CO2 to the atmosphere. This study reports one of the first geochemical and isotopic studies of such “anthropogenic” pedogenic carbonates and CO2 from irrigated drylands of southwestern United States. A pecan orchard and an alfalfa field, where flood-irrigation using the Rio Grande river is a common practice, were compared to a nearby natural dryland site. Strontium and carbon isotope ratios show that bulk pedogenic carbonates in irrigated soils at the pecan orchard primarily formed due to flood-irrigation, and that approximately 20–50% of soil CO2 in these irrigated soils is calcite-derived abiotic CO2 instead of soil-respired or atmospheric origins. Multiple variables that control the salt buildup in this region are identified and impact the crop production and soil sustainability regionally and globally. Irrigation intensity and water chemistry (irrigation water quantity and quality) dictate salt loading, and soil texture governs water infiltration and salt leaching. In the study area, agricultural soils have accumulated up to 10 wt% of calcite after just about 100 years of cultivation. These rates will likely increase in the future due to the combined effects of climate variability (reduced rainfall and more intense evaporation), use of more brackish groundwater for irrigation, and reduced porosity in soils. The enhanced accumulation rates of pedogenic carbonate are accompanied by release of large amounts of abiotic CO2 from irrigated drylands to atmosphere. Extensive field studies and modelling approaches are needed to further quantify these effluxes at local, regional and global scales.
Intense ocean freshening from melting glacier around the Antarctica during early twenty-first century
Authors: Pan Xianliang L. , Li Bofeng F. , Watanabe Yutaka W.
Published: January 2022

With the accelerating mass loss of Antarctic ice sheets, the freshening of the Southern Ocean coastal oceans (SOc, seas around Antarctica) is gradually intensifying, which will reduce the formation of bottom water and weaken the meridional overturning circulation, thus having a significant negative impact on the ocean’s role in regulating global climate. Due to the extreme environment of the Southern Ocean and the limitations of observational techniques, our understanding of the glacier-derived freshening of SOc is still vague. We developed a method that first provided us with an expansive understanding of glacier-derived freshening progress over the SOc. Applying this method to the observational data in the SOc from 1926 to 2016, revealed that the rate of glacier-derived freshwater input reached a maximum of 268 ± 134 Gt year−1 during the early twenty-first century. Our results indicate that during the same period, glacier melting accounted for 63%, 28%, and 92% of the total freshening occurred in the Atlantic, Indian, and Pacific sectors of the SOc, respectively. This suggests that the ice shelf basal melt in West Antarctica and the Antarctic Peninsula plays a dominant role in the freshening of the surrounding seas.
Polarization insensitive symmetrical structured double negative (DNG) metamaterial absorber for Ku-band sensing applications
Authors: Hakim Mohammad Lutful , Alam Touhidul , Soliman Mohamed S. , Sahar Norsuzlin Mohd , Baharuddin Mohd Hafiz , Almalki Sami H. A. , Islam Mohammad Tariqul
Published: January 2022

Metamaterial absorber (MMA) is now attracting significant interest due to its attractive applications, such as thermal detection, sound absorption, detection for explosive, military radar, wavelength detector, underwater sound absorption, and various sensor applications that are the vital part of the internet of things. This article proposes a modified square split ring resonator MMA for Ku-band sensing application, where the metamaterial structure is designed on FR-4 substrate material with a dielectric constant of 4.3 and loss tangent of 0.025. Perfect absorption is realized at 14.62 GHz and 16.30 GHz frequency bands, where peak absorption is about 99.99% for both frequency bands. The proposed structure shows 70% of the average absorption bandwidth of 420 MHz (14.42–14.84 GHz) and 480 MHz (16.06–16.54 GHz). The metamaterial property of the proposed structure is investigated for transverse electromagnetic mode (TEM) and achieved negative permittivity, permeability, and refractive index property for each absorption frequency band at 0°, 45°, and 90° polarization angles. Interference theory is also investigated to verify the absorption properties. Moreover, the permittivity sensor application is investigated to verify the sensor performance of the proposed structure. Finally, a comparison with recent works is performed, which shows that the proposed MMA can be a good candidate for Ku-band perfect absorber and sensing applications.
Therapeutic outcome of active management in male patients with detrusor underactivity based on clinical diagnosis and videourodynamic classification
Authors: Lee Cheng-Ling , Jhang Jia-Fong , Ho Han-Chen , Jiang Yuan-Hong , Hsu Yuan-Hsiang , Kuo Hann-Chorng
Published: January 2022

Detrusor underactivity (DU) could be resulted from many different etiologies. Patients with DU might have reduced bladder sensation, low detrusor contractility, and large post-void residual volume. This study analyzed therapeutic outcome of active management for male DU patients, based on clinical and urodynamic characteristics. Male DU patients aged > 18 years old were retrospectively reviewed from the videourodynamic study (VUDS) records in recent 10 years. The patients’ demographics, VUDS results, treatment modalities, and treatment outcome were analyzed. The treatment outcomes were compared among patients with different DU subgroups, clinical diagnosis and treatment modalities. Patients with voiding efficiency of > 66.7% were considered having a successful treatment outcome. For comparison, 30 men with normal VUDS finding served as the control arm. Most of the DU patients had reduced bladder sensation. The reduced bladder sensation is closely associated with low detrusor contractility. After active treatment, a successful outcome was achieved in 68.4% of patients after bladder outlet surgery, 59.1% after urethral botulinum toxin A injection, and 57.6% after medical treatment, but only 18.2% after conservative treatment. A successful treatment outcome was achieved in patients with an intact detrusor contractility, either low (69.2%) or normal voiding pressure (81.8%), and in patients with a normal or increased bladder sensation (78.1%). However, patients with detrusor acontractile (41.3%) or absent bladder sensation (17.9%) had less favorable treatment outcome after any kind of urological management. This study revealed that active management can effectively improve voiding efficiency in patients with DU. The normal bladder sensation, presence of adequate detrusor contractility, and bladder outlet narrowing during VUDS provide effective treatment strategy for DU patients. Among all management, BOO surgery provides the best treatment outcome.
Increased climate pressure on the agricultural frontier in the Eastern Amazonia–Cerrado transition zone
Authors: Marengo José A. , Jimenez Juan C. , Espinoza Jhan-Carlo , Cunha Ana Paula , Aragão Luiz E. O.
Published: January 2022

Several large-scale drivers of both anthropogenic and natural environmental changes are interacting nonlinearly in the transition zone between eastern Amazonia and the adjacent Cerrado, considered to be another Brazilian agricultural frontier. Land-use change for agrobusiness expansion together with climate change in the transition zone between eastern Amazonia and the adjacent Cerrado may have induced a worsening of severe drought conditions over the last decade. Here we show that the largest warming and drying trends over tropical South America during the last four decades are observed to be precisely in the eastern Amazonia–Cerrado transition region, where they induce delayed wet-season and worsen severe drought conditions over the last decade. Our results evidence an increase in temperature, vapor pressure deficit, subsidence, dry-day frequency, and a decrease in precipitation, humidity, and evaporation, plus a delay in the onset of the wet season, inducing a higher risk of fire during the dry-to-wet transition season. These findings provide observational evidence of the increasing climatic pressure in this area, which is sensitive for global food security, and the need to reconcile agricultural expansion and protection of natural tropical biomes.
Possibility of adiponectin use to improve islet transplantation outcomes
Authors: Sakata Naoaki , Yoshimatsu Gumpei , Chinen Kiyoshi , Kawakami Ryo , Kodama Shohta
Published: January 2022

Although islet transplantation (ITx) is a promising therapy for severe diabetes mellitus, further advancements are necessary. Adiponectin, an adipokine that regulates lipid and glucose metabolism, exerts favorable effects on islets, such as reinforcement of the insulin-releasing function. This study evaluated the possibility of adiponectin use to improve ITx outcomes. We treated mouse islets with 10 µg/mL recombinant mouse adiponectin by overnight culture and then assessed the insulin-releasing, angiogenic, and adhesion functions of the islets. Furthermore, 80 syngeneic islet equivalents with or without adiponectin treatment were transplanted into the renal subcapsular space of diabetic mice. In in vitro assessment, released insulin at high glucose stimulation, insulin content, and expressions of vascular endothelial growth factor and integrin β1 were improved in adiponectin-treated islets. Furthermore, adiponectin treatment improved the therapeutic effect of ITx on blood glucose levels and promoted angiogenesis of the transplanted islets. However, the therapeutic effect was not pronounced in glucose tolerance test results. In conclusion, adiponectin treatment had preferable effects in the insulin-releasing, angiogenic, and adhesion functions of islets and contributed to the improvement of ITx. The future use of adiponectin treatment in clinical settings to improve ITx outcomes should be investigated.
Prevalence and impact of visual aura in migraine and probable migraine: a population study
Authors: Kim Kyung Min , Kim Byung-Kun , Lee Wonwoo , Hwang Heewon , Heo Kyoung , Chu Min Kyung
Published: January 2022

Visual aura (VA) presents in 98% of cases of migraine with aura. However, data on its prevalence and impact in individuals with migraine and probable migraine (PM) are limited. Data from the nation-wide, population-based Circannual Change in Headache and Sleep Study were collected. Participants with VA rating scale scores ≥ 3 were classified as having VA. Of 3,030 participants, 170 (5.6%) and 337 (11.1%) had migraine and PM, respectively; VA prevalence did not differ between these cohorts (29.4% [50/170] vs. 24.3% [82/337], p = 0.219). Participants with migraine with VA had a higher headache frequency per month (4.0 [2.0–10.0] vs. 2.0 [1.0–4.8], p = 0.014) and more severe cutaneous allodynia (12-item Allodynia Symptom Checklist score; 3.0 [1.0–8.0] vs. 2.0 [0.0–4.8], p = 0.046) than those without VA. Participants with PM with VA had a higher headache frequency per month (2.0 [2.0–8.0] vs. 2.0 [0.6–4.0], p = 0.001), greater disability (Migraine Disability Assessment score; 10.0 [5.0–26.3] vs. 5.0 [2.0–12.0], p < 0.001), and more severe cutaneous allodynia (12-item Allodynia Symptom Checklist score, 2.5 [0.0–6.0] vs. 0.0 [0.0–3.0], p < 0.001) than those without VA. VA prevalence was similar between migraine and PM. Some symptoms were more severe in the presence of VA.
The differential effects of tumor burdens on predicting the net benefits of ssCART-19 cell treatment on r/r B-ALL patients
Authors: Li Minghao , Xue Sheng-Li , Tang Xiaowen , Xu Jiayu , Chen Suning , Han Yue , Qiu Huiying , Miao Miao , Xu Nan , Tan Jingwen , Kang Liqing , Yu Zhou , Lou Xiaoyan , Xu Yang , Chen Jia , Yan Zhiqiang , Feng Weixing , Wu Depei , Yu Lei
Published: January 2022

The tumor burden (TB) is significantly related to the severity of cytokine release syndrome (CRS) caused by CAR-T cells, but its correlation with therapeutic efficacy has not been systematically studied. This study focused on the effects of the TB level on both the safety and efficacy of ssCART-19 as a treatment for r/r B-ALL. Taking the 5% tumor burden as the boundary, the study participants were divided into 2 groups, high and low tumor burden groups. Under this grouping strategy, the impacts of differential r/r B-ALL TBs on the clinical therapeutic efficacy (CR rate and long-term survival) and safety profiles after ssCART-19 cell treatment were analysed. 78 patients were reported in this study. The differential B-ALL TBs significantly affected the complete remission (CR) rates of patients treated with ssCART-19, with rates of 93.94% and 75.56% in the low and high TB groups, respectively (P = 0.0358). The effects of TBs on long-term therapeutic efficacy were further studied based on event-free survival (EFS) and overall survival (OS) profiles; both the OS and EFS of the low TB group were better than those of the high TB group, but the differences were not statistically significant. Importantly, the time points of TB measurement did not significantly affect the OS and EFS profiles regardless of whether the TBs were measured before or after fludarabine-cyclophosphamide (FC) preconditional chemotherapy. On the other hand, the severity of CRS was significantly correlated with the TB level (P = 0.0080), and the incidence of sCRS was significantly related to the TB level (the sCRS incidence increased as the TB level increased, P = 0.0224). Unexpectedly, the ssCART-19 cell expansion peaks were not significantly different (P = 0.2951) between the study groups. Patients with a low r/r B-ALL TB yield more net benefits from CAR-T treatment than those with a high TB in terms of safety and CR rate. These findings are critical and valuable for determining the optimal CAR-T cell treatment window for r/r B-ALL patients and will further the development of comprehensive and reasonable CAR-T cell treatment plans for r/r B-ALL patients with differential TBs.

Trial registration: ClinicalTrials.gov identifier, NCT03919240.
Effective prediction of short hydrogen bonds in proteins via machine learning method
Authors: Zhou Shengmin , Liu Yuanhao , Wang Sijian , Wang Lu
Published: January 2022

Short hydrogen bonds (SHBs), whose donor and acceptor heteroatoms lie within 2.7 Å, exhibit prominent quantum mechanical characters and are connected to a wide range of essential biomolecular processes. However, exact determination of the geometry and functional roles of SHBs requires a protein to be at atomic resolution. In this work, we analyze 1260 high-resolution peptide and protein structures from the Protein Data Bank and develop a boosting based machine learning model to predict the formation of SHBs between amino acids. This model, which we name as machine learning assisted prediction of short hydrogen bonds (MAPSHB), takes into account 21 structural, chemical and sequence features and their interaction effects and effectively categorizes each hydrogen bond in a protein to a short or normal hydrogen bond. The MAPSHB model reveals that the type of the donor amino acid plays a major role in determining the class of a hydrogen bond and that the side chain Tyr-Asp pair demonstrates a significant probability of forming a SHB. Combining electronic structure calculations and energy decomposition analysis, we elucidate how the interplay of competing intermolecular interactions stabilizes the Tyr-Asp SHBs more than other commonly observed combinations of amino acid side chains. The MAPSHB model, which is freely available on our web server, allows one to accurately and efficiently predict the presence of SHBs given a protein structure with moderate or low resolution and will facilitate the experimental and computational refinement of protein structures.
3-D twelve-port multi-service diversity antenna for automotive communications
Authors: Kannappan Lekha , Palaniswamy Sandeep Kumar , Kanagasabai Malathi , Kumar Preetam , Alsath M. Gulam Nabi , Kumar Sachin , Rao Thipparaju Rama , Marey Mohamed , Aggarwal Apeksha , Pakkathillam Jayaram K.
Published: January 2022

This paper presents a twelve-port ultra-wideband multiple-input-multiple-output (MIMO)/diversity antenna integrated with GSM and Bluetooth bands. The twelve-port antenna is constructed by arranging four elements in the horizontal plane and eight elements in the vertical plane. The antenna element, which is created using a simple rectangular monopole, exhibits a frequency range of 3.1 to 12 GHz. The additional Bluetooth and GSM bands are achieved by introducing stubs into the ground plane. The size of the MIMO antenna is 100 × 100 mm2. The antenna offers polarization diversity, with vertical and horizontal polarization in each plane. The diversity antenna has a bandwidth of 1.7–1.9 GHz, 2.35–2.55 GHz, and 3–12 GHz, the radiation efficiency of 90%, and peak gain of 2.19 dBi. The proposed antenna offers an envelope correlation coefficient of < 0.12, apparent diversity gain of > 9.9 dB, effective diversity gain of > 8.9 dB, mean effective gain of < 1 dB, and channel capacity loss of < 0.35 bits/s/Hz. Also, the MIMO antenna is tested for housing effects in order to determine its suitability for automotive applications.
Longitudinal genome-wide DNA methylation changes in response to kidney failure replacement therapy
Authors: Witasp Anna , Luttropp Karin , Qureshi Abdul Rashid , Barany Peter , Heimbürger Olof , Wennberg Lars , Ekström Tomas J. , Shiels Paul G. , Stenvinkel Peter , Nordfors Louise
Published: January 2022

Chronic kidney disease (CKD) is an emerging public health priority associated with high mortality rates and demanding treatment regimens, including life-style changes, medications or even dialysis or renal transplantation. Unavoidably, the uremic milieu disturbs homeostatic processes such as DNA methylation and other vital gene regulatory mechanisms. Here, we aimed to investigate how dialysis or kidney transplantation modifies the epigenome-wide methylation signature over 12 months of treatment. We used the Infinium HumanMethylation450 BeadChip on whole blood samples from CKD-patients undergoing either dialysis (n = 11) or kidney transplantation (n = 12) and 24 age- and sex-matched population-based controls. At baseline, comparison between patients and controls identified several significant (PFDR < 0.01) CpG methylation differences in genes with functions relevant to inflammation, cellular ageing and vascular calcification. Following 12 months, the global DNA methylation pattern of patients approached that seen in the control group. Notably, 413 CpG sites remained differentially methylated at follow-up in both treatment groups compared to controls. Together, these data indicate that the uremic milieu drives genome-wide methylation changes that are partially reversed with kidney failure replacement therapy. Differentially methylated CpG sites unaffected by treatment may be of particular interest as they could highlight candidate genes for kidney disease per se.
Relevance of gene mutations and methylation to the growth of pancreatic intraductal papillary mucinous neoplasms based on pyrosequencing
Authors: Asano Go , Miyabe Katsuyuki , Kato Hiroyuki , Yoshida Michihiro , Sawada Takeshi , Okamoto Yasuyuki , Sahashi Hidenori , Atsuta Naoki , Kachi Kenta , Kato Akihisa , Jinno Naruomi , Natsume Makoto , Hori Yasuki , Naitoh Itaru , Hayashi Kazuki , Matsuo Yoichi , Takahashi Satoru , Suzuki Hiromu , Kataoka Hiromi
Published: January 2022

We aimed to assess some of the potential genetic pathways for cancer development from non-malignant intraductal papillary mucinous neoplasm (IPMN) by evaluating genetic mutations and methylation. In total, 46 dissected regions in 33 IPMN cases were analyzed and compared between malignant-potential and benign cases, or between malignant-potential and benign tissue dissected regions including low-grade IPMN dissected regions accompanied by malignant-potential regions. Several gene mutations, gene methylations, and proteins were assessed by pyrosequencing and immunohistochemical analysis. RASSF1A methylation was more frequent in malignant-potential dissected regions (p = 0.0329). LINE-1 methylation was inversely correlated with GNAS mutation (r =  − 0.3739, p = 0.0105). In cases with malignant-potential dissected regions, GNAS mutation was associated with less frequent perivascular invasion (p = 0.0128), perineural invasion (p = 0.0377), and lymph node metastasis (p = 0.0377) but significantly longer overall survival, compared to malignant-potential cases without GNAS mutation (p = 0.0419). The presence of concordant KRAS and GNAS mutations in the malignant-potential and benign dissected regions were more frequent among branch-duct IPMN cases than among the other types (p = 0.0319). Methylation of RASSF1A, CDKN2A, and LINE-1 and GNAS mutation may be relevant to cancer development, IPMN subtypes, and cancer prognosis.
Endothelial-derived extracellular microRNA-92a promotes arterial stiffness by regulating phenotype changes of vascular smooth muscle cells
Authors: Wang Chen , Wu Haoyu , Xing Yuanming , Ye Yulan , He Fangzhou , Yin Qian , Li Yujin , Shang Fenqing , Shyy John Y.-J. , Yuan Zu-Yi
Published: January 2022

Endothelial dysfunction and vascular smooth muscle cell (VSMC) plasticity are critically involved in the pathogenesis of hypertension and arterial stiffness. MicroRNAs can mediate the cellular communication between vascular endothelial cells (ECs) and neighboring cells. Here, we investigated the role of endothelial-derived extracellular microRNA-92a (miR-92a) in promoting arterial stiffness by regulating EC–VSMC communication. Serum miR-92a level was higher in hypertensive patients than controls. Circulating miR-92a level was positively correlated with pulse wave velocity (PWV), systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum endothelin-1 (ET-1) level, but inversely with serum nitric oxide (NO) level. In vitro, angiotensin II (Ang II)-increased miR-92a level in ECs mediated a contractile-to-synthetic phenotype change of co-cultured VSMCs. In Ang II-infused mice, locked nucleic acid-modified antisense miR-92a (LNA-miR-92a) ameliorated PWV, SBP, DBP, and impaired vasodilation induced by Ang II. LNA-miR-92a administration also reversed the increased levels of proliferative genes and decreased levels of contractile genes induced by Ang II in mouse aortas. Circulating serum miR-92a level and PWV were correlated in these mice. These findings indicate that EC miR-92a may be transported to VSMCs via extracellular vesicles to regulate phenotype changes of VSMCs, leading to arterial stiffness.
The impact of methodology on the reproducibility and rigor of DNA methylation data
Authors: Boison Detlev , Masino Susan A. , Lubin Farah D. , Guo Kai , Lusardi Theresa , Sanchez Richard , Ruskin David N. , Ohm Joyce , Geiger Jonathan D. , Hur Junguk
Published: January 2022

Epigenetic modifications are crucial for normal development and implicated in disease pathogenesis. While epigenetics continues to be a burgeoning research area in neuroscience, unaddressed issues related to data reproducibility across laboratories remain. Separating meaningful experimental changes from background variability is a challenge in epigenomic studies. Here we show that seemingly minor experimental variations, even under normal baseline conditions, can have a significant impact on epigenome outcome measures and data interpretation. We examined genome-wide DNA methylation and gene expression profiles of hippocampal tissues from wild-type rats housed in three independent laboratories using nearly identical conditions. Reduced-representation bisulfite sequencing and RNA-seq respectively identified 3852 differentially methylated and 1075 differentially expressed genes between laboratories, even in the absence of experimental intervention. Difficult-to-match factors such as animal vendors and a subset of husbandry and tissue extraction procedures produced quantifiable variations between wild-type animals across the three laboratories. Our study demonstrates that seemingly minor experimental variations, even under normal baseline conditions, can have a significant impact on epigenome outcome measures and data interpretation. This is particularly meaningful for neurological studies in animal models, in which baseline parameters between experimental groups are difficult to control. To enhance scientific rigor, we conclude that strict adherence to protocols is necessary for the execution and interpretation of epigenetic studies and that protocol-sensitive epigenetic changes, amongst naive animals, may confound experimental results.
An assessment of irrigated rice cultivation with different crop establishment practices in Vietnam
Authors: Nguyen Van-Hung , Stuart Alexander M. , Nguyen Thi-My-Phung , Pham Thi-Minh-Hieu , Nguyen Ngoc-Phuong-Thanh , Pame Anny Ruth P. , Sander Bjoern Ole , Gummert Martin , Singleton Grant Robert
Published: January 2022

Overuse of seed and chemical inputs is a major constraint for sustainable rice production in Vietnam. In this study, two seasons of field trials were conducted to compare different crop establishment practices for rice production in the Mekong River Delta using environmental and economic sustainability performance indicators. The indicators including energy efficiency, agronomic use efficiency, net income, and greenhouse gas emissions (GHGEs) were quantified based on four treatments including manual broadcast-seeding, blower seeding, drum seeding, and mechanized transplanting. Across the four treatments, yields ranged from 7.3–7.5 Mg ha−1 and 6.2–6.8 Mg ha−1 in the Winter-Spring (WS) and Summer-Autumn (SA) seasons, respectively. In comparison with direct seeding methods, mechanized transplanting decreased the seed rate by 40%. It also led to a 30–40% reduction in pesticide use during the main crop season (WS). Mechanized transplanting required higher inputs, including machine depreciation and fuel consumption, but its net energy balance, net income and GHGE were at a similar level as the other non-mechanized planting practices. Mechanized transplanting is a technology package that should be promoted to improve the economic and environmental sustainability of lowland rice cultivation in the Mekong River Delta of Vietnam.
Non-invasive scoring of cellular atypia in keratinocyte cancers in 3D LC-OCT images using Deep Learning
Authors: Fischman Sébastien , Pérez-Anker Javiera , Tognetti Linda , Di Naro Angelo , Suppa Mariano , Cinotti Elisa , Viel Théo , Monnier Jilliana , Rubegni Pietro , del Marmol Véronique , Malvehy Josep , Puig Susana , Dubois Arnaud , Perrot Jean-Luc
Published: January 2022

Diagnosis based on histopathology for skin cancer detection is today’s gold standard and relies on the presence or absence of biomarkers and cellular atypia. However it suffers drawbacks: it requires a strong expertise and is time-consuming. Moreover the notion of atypia or dysplasia of the visible cells used for diagnosis is very subjective, with poor inter-rater agreement reported in the literature. Lastly, histology requires a biopsy which is an invasive procedure and only captures a small sample of the lesion, which is insufficient in the context of large fields of cancerization. Here we demonstrate that the notion of cellular atypia can be objectively defined and quantified with a non-invasive in-vivo approach in three dimensions (3D). A Deep Learning (DL) algorithm is trained to segment keratinocyte (KC) nuclei from Line-field Confocal Optical Coherence Tomography (LC-OCT) 3D images. Based on these segmentations, a series of quantitative, reproducible and biologically relevant metrics is derived to describe KC nuclei individually. We show that, using those metrics, simple and more complex definitions of atypia can be derived to discriminate between healthy and pathological skins, achieving Area Under the ROC Curve (AUC) scores superior than 0.965, largely outperforming medical experts on the same task with an AUC of 0.766. All together, our approach and findings open the door to a precise quantitative monitoring of skin lesions and treatments, offering a promising non-invasive tool for clinical studies to demonstrate the effects of a treatment and for clinicians to assess the severity of a lesion and follow the evolution of pre-cancerous lesions over time.
Substantial rearrangements, single nucleotide frameshift deletion and low diversity in mitogenome of Wolbachia-infected strepsipteran endoparasitoid in comparison to its tephritid hosts
Authors: Towett-Kirui Sharon , Morrow Jennifer L. , Riegler Markus
Published: January 2022

Insect mitogenome organisation is highly conserved, yet, some insects, especially with parasitic life cycles, have rearranged mitogenomes. Furthermore, intraspecific mitochondrial diversity can be reduced by fitness-affecting bacterial endosymbionts like Wolbachia due to their maternal coinheritance with mitochondria. We have sequenced mitogenomes of the Wolbachia-infected endoparasitoid Dipterophagus daci (Strepsiptera: Halictophagidae) and four of its 22 known tephritid fruit fly host species using total genomic extracts of parasitised flies collected across > 700 km in Australia. This halictophagid mitogenome revealed extensive rearrangements relative to the four fly mitogenomes which exhibited the ancestral insect mitogenome pattern. Compared to the only four available other strepsipteran mitogenomes, the D. daci mitogenome had additional transpositions of one rRNA and two tRNA genes, and a single nucleotide frameshift deletion in nad5 requiring translational frameshifting or, alternatively, resulting in a large protein truncation. Dipterophagus daci displays an almost completely endoparasitic life cycle when compared to Strepsiptera that have maintained the ancestral state of free-living adults. Our results support the hypothesis that the transition to extreme endoparasitism evolved together with increased levels of mitogenome changes. Furthermore, intraspecific mitogenome diversity was substantially smaller in D. daci than the parasitised flies suggesting Wolbachia reduced mitochondrial diversity because of a role in D. daci fitness.
A comparative study of an Yb-doped fiber gain-managed nonlinear amplifier seeded by femtosecond fiber lasers
Authors: Tomaszewska-Rolla Dorota , Lindberg Robert , Pasiskevicius Valdas , Laurell Fredrik , Soboń Grzegorz
Published: January 2022

In this work, we show that the nonlinear evolution of femtosecond seed pulses with different parameters (temporal and spectral shapes, repetition rate, pulse energy) in an Yb-fiber amplifier leads to gain-managed nonlinear amplification, enabling robust generation of high-peak-power and nearly transform-limited pulses after external compression. We demonstrate a compressed pulse duration of 33 fs with an energy of 80.5 nJ and a peak power of 2.29 MW for a source with a repetition rate of 30 MHz. For a second seed source with a repetition rate of 125 MHz, we obtained a pulse duration of 51 fs with an energy of 22.8 nJ and a peak power of 420 kW. Numerical simulations incorporating rate equations and nonlinear propagation in the amplifier provide evolutions that agree well with the experimental results. The discrepancies in the amplifier’s absorption edge appearing at low repetition rates and higher pump powers are attributed to the temperature dependence of the amplifier’s gain cross-sections. Here, we experimentally verify this attribution and thus underline the importance of accounting for the fiber core temperature for precise modelling of the short-wavelength spectral edge of the output pulses in nonlinear Yb-fiber amplifiers. We also measure, for the first time, the relative intensity noise of an amplifier operating in the gain-managed nonlinear regime. The measurements reveal a significant contribution of the amplification process to the overall output noise of the system.