bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcatheter aortic valve replacement in patients undergoing robotic totally endoscopic coronary artery bypass: A case series
Authors: Srivastava Ankur , Smazil Jennifer , Roark Lauren , Shah Hayla A. , Balkhy Husam H. , Shah Atman P.
Published: September 2022

Transcatheter aortic valve replacement (TAVR) has been utilized to treat patients with symptomatic aortic stenosis (AS). Recent trials suggest comparable efficacy compared to surgical aortic valve replacement (SAVR). Robotic off-pump totally endoscopic coronary artery bypass graft surgery (TECAB) had been shown to be a minimally invasive revascularization strategy with clinical results comparable to traditional coronary artery bypass graft surgery (CABG). Traditionally, pre-surgical coronary evaluation is considered necessary to optimize coronary revascularization at the time of AVR. The 2020 ACC/AHA Guideline for the Management of Patients with Valvular Disease gives a moderate recommendation, based on limited data, for CABG at the time of AVR in patients with significant coronary artery disease (CAD). This paper presents two patients with known significant CAD awaiting robotic TECAB who were treated with TAVR, prior to surgical revascularization. Robotic TECAB is unique in that it offers patients the ability to have complete coronary revascularization without a sternotomy and with early ambulation, discharge, and recovery. The case series demonstrates a hybrid approach that offers complete sternotomy sparing cardiovascular care to treat severe symptomatic AS and CAD. Since patients with severe aortic stenosis are at high risk of developing cardiac arrest and cardiogenic shock upon induction of anesthesia, the ability to treat severe symptomatic AS with TAVR under conscious sedation prior to TECAB can be considered as a safe an effective treatment.
A novel interpretable machine learning algorithm to identify optimal parameter space for cancer growth
Authors: Coggan Helena , Andres Terre Helena , Liò Pietro
Published: September 2022

Recent years have seen an increase in the application of machine learning to the analysis of physical and biological systems, including cancer progression. A fundamental downside to these tools is that their complexity and nonlinearity makes it almost impossible to establish a deterministic, a priori relationship between their input and output, and thus their predictions are not wholly accountable. We begin with a series of proofs establishing that this holds even for the simplest possible model of a neural network; the effects of specific loss functions are explored more fully in Appendices. We return to first principles and consider how to construct a physics-inspired model of tumor growth without resorting to stochastic gradient descent or artificial nonlinearities. We derive an algorithm which explores the space of possible parameters in a model of tumor growth and identifies candidate equations much faster than a simulated annealing approach. We test this algorithm on synthetic tumor-growth trajectories and show that it can efficiently and reliably narrow down the area of parameter space where the correct values are located. This approach has the potential to greatly improve the speed and reliability with which patient-specific models of cancer growth can be identified in a clinical setting.
Three-dimensional displacement field of the 2010 Mw 8.8 Maule earthquake from GPS and InSAR data with the improved ESISTEM-VCE method
Authors: Xiong Luyun , Xu Caijun , Liu Yang , Zhao Yingwen , Geng Jianghui , Ortega-Culaciati Francisco
Published: September 2022

The 2010 Mw 8.8 Maule earthquake occurred offshore central Chile and ruptured ∼500 km along the megathrust fault resulting from the oceanic Nazca plate subducting beneath the continental South American plate. The Maule earthquake produced remnant crustal displacements captured by a vast set of geodetic observations. However, given the nature of the observational techniques, it is challenging to extract its accurate three-dimensional coseismic deformation field with high spatial resolution. In this study, we modified the extended simultaneous and integrated strain tensor estimation from geodetic and satellite deformation measurements (ESISTEM) method with variance component estimation algorithm (ESISTEM-VCE) to retrieve the three-dimensional surface displacement field of this event by integrating the interferometric synthetic aperture radar (InSAR) and global positioning system (GPS) measurements. The ESISTEM-VCE method accounts for the spatial correlation of surface displacement among the adjacent points and determine the accurate weight ratios for different data sets, but also uses the uncertainties of GPS data and considers the different spatial scales from the different datasets. In the simulation experiments, the RMSEs of the ESISTEM-VCE method are smaller than those of the ESISTEM and ESISTEM-VCE (same d0) methods, and the improvements of 97.1%, 3.9%, and 84% are achieved in the east-west, north-south, and vertical components, respectively. Then, we apply the proposed methodology to the 2010 Mw 8.8 Maule earthquake, to obtain a three-dimensional displacement field that could provide fine deformation information. In the east-west component, the significant deformation is in the north of the epicenter, closed to the Constitución, with a maximum westward displacement of 495.5 cm. The displacement in the north-south component is relatively small compared to that in the east-west component. The maximum uplift reaches 211.8 cm, located at the southwest of the Concepción. Finally, the derived vertical displacements are also compared with field investigations, indicating that the ESISTEM-VCE method can obtain more accurate weight of different datasets and perform better than the ESISTEM method. The results highlight that the earthquake ruptured along the NE-SW direction, with a dominant thrust and a relatively small component of right-lateral strike-slip, coinciding with the characteristics of subduction and right-lateral shear. The experiments with the simulated and real data suggest that the improved ESISTEM-VCE method in this study is feasible and effective.
Spatial- and temporal-interpolations for efficient hybrid wave numerical simulations
Authors: Shen Hao , Tang Xiaotian , Lyu Chao , Zhao Liang
Published: September 2022

The hybrid simulation method is developed for simulating wave propagation only in a localized heterogeneous media with hybrid inputs obtained once for all from a known reference model. Despite the fact that the hybrid simulation method has a wide range of applications in computational seismology, the associated error control of this method has received relatively little attention in previous research works. We quantitatively discuss the error of the two-step hybrid method in acoustic wave cases and propose a spatial refinement scheme to compute hybrid inputs based on the multi-elements spline interpolation, which is preferable to traditional Lagrange interpolation since it uses more polydirectional interpolated points. This method can also be used for local refinement of wavefield in more general applications, such as saving smooth wavefield in the full-waveform inversion framework. Furthermore, to save memory requirements, hybrid inputs are proposed to be sparsely stored with a high upsampling ratio during the global simulation, and the Fourier interpolation method is introduced to recover them to their original time series. To demonstrate the effect of the proposed methods, we perform several 2D and 3D hybrid wave numerical simulations using the spectral element method. We find that when the global and local meshing differs, the proposed spatial interpolation method can appreciably reduce the error of the hybrid waveforms caused by inaccurate hybrid inputs. We also point out that the Fourier interpolation can efficiently recover the original waveform, allowing hybrid inputs to be stored with time steps toward the Nyquist limit. Our method is expected to become a standard method to reduce the error of hybrid waveforms and save the memory requirements during hybrid simulations and has potential implications for further improving the accuracy of the so-called box tomography.
Paleoearthquakes of the Yangda-Yaxu fault across the Nujiang suture and Lancang river suture zone, southeastern Tibetan Plateau
Authors: Han Mingming , Chen Lichun , Li Yanbao , Gao Shuaipo , Feng Jiahui
Published: September 2022

The WNW-trending Yangda-Yaxu fault (YYF) is located in the interior of the Qiangtang block (QTB). The YYF cuts through the Nujiang suture and Lancang river suture zone and divides Nujiang fault (NF) and Lancangjiang fault (LCJF) into two sections with significantly different activity levels, suggesting that the YYF may function as a specific structure in this region. In addition, a recent work argues that the YYF plays an important role in strain partitioning in southeastern Tibet and poses a high surface-faulting risk to the Sichuan-Tibet railway. However, no M ≥ 5.0 earthquakes have been recorded, and no palaeoseismic research has been conducted along the fault, leading to limited knowledge regarding its rupture behavior, which is essential for understanding regional tectonic deformation and assessing the regional seismic potential. In this study, we constrained the timings and recurrence intervals of late Quaternary paleoseismic events along the YYF for the first time. Through trench excavations and exposure cleaning combined with radiocarbon dating, five faulting events were identified, namely, E1 through E5 from youngest to oldest (831–1,220, 3,307–6,703, 9,361–10,286, 12,729–14,651, and before 14,651 yr BP). The recurrence interval of major earthquakes along the YYF follows a quasi-periodic pattern with an interval of ∼4,000 yr. Combining the clear linear geomorphic features along the fault and the paleoearthquake results in this paper, we believe that YYF is a newly-generated active fault, and has a significant control effect on the late Quaternary evolution of the NF and the LCJF. Further analysis revealed that the YYF also plays an important role in accommodating crustal deformation.
Patterns of observed child participation and proximity to a small group including teachers in Swedish preschool free play
Authors: Åström Frida , Almqvist Lena
Published: September 2022

The participation of all children in preschool activities is the main outcome of inclusive Early Childhood Education and Care (ECEC). The current study used the Child Observation in Preschool (COP) to explore the observed participation patterns in the free play of a sample of 3–5-year-old Swedish preschool children (N = 453), and to examine the characteristics of the resulting clusters in terms of child and preschool unit characteristics. Based on a series of hierarchical and K-means cluster analyses, we identified eight distinct and meaningful clusters that could be ranked from very high to very low observed participation. Four of the clusters indicated average-to-very high observed participation. Two clusters indicated low-to-very low observed participation. The cluster displaying low observed participation had high proximity to a small group including teachers. On average, children in this cluster came from preschool units with significantly more second language learners. The cluster displaying a very low observed participation had low proximity to a small group including teachers. On average, children in this cluster were significantly more often second language learners, and the children came from units with a significantly higher number of resource staff. No significant differences appeared in the number of children with special educational needs across the clusters, although tendencies emerged. The results imply that the children in this sample had a varied degree of observed participation. Two clusters of children appeared to have difficulties in participating in free play activities where second language learners and children from preschool units with more second language learners were more common. Preschool teachers need to identify children who participate less in preschool activities and who might benefit from more teacher proximity. Teachers also need to reflect on how their proximity impacts the participation of children differently and on the type of support they provide when being close to the children.
An empirical analysis of talent policy, executive incentive, and enterprise green technological innovation based on China’s A-share listed companies
Authors: Zhang Yuan-Bo , Qu Shi-You , Li Hai-Bo , Li Miao-Miao
Published: September 2022

This article investigates how talent policies affect corporate green technological innovation through executive incentive strategies based on signaling theory and principal-agent theory, by examining samples from 1,536 A-share listed companies between 2010 and 2020. The findings indicate that talent policy helps enterprises boost green technological innovation while accelerating it by improving executive compensation incentives. This effect path is more significant in high-tech enterprises and enterprises with weak solvency ratios. However, we find that the current talent policy has inhibited the green innovation of enterprises. The conclusions provide micro-evidence for the impact mechanism by which talent policy affects enterprise green technological innovation and offer scientifically based guidelines for optimizing talent policy to promote innovation-driven development strategy.
Reviewing the links and feedbacks between climate change and air pollution in Europe
Authors: Im Ulas , Geels Camilla , Hanninen Risto , Kukkonen Jaakko , Rao Shilpa , Ruuhela Reija , Sofiev Mikhail , Schaller Nathalie , Hodnebrog Øivind , Sillmann Jana , Schwingshackl Clemens , Christensen Jesper H. , Bojariu Roxana , Aunan Kristin
Published: September 2022

Feedbacks between air pollutants and meteorology play a crucial role in the direction of the response of future climate and air pollution. These feedbacks are important to understand and quantify the potential impact of adaptation and mitigation policies setup for protecting the population against air pollution and heat stress. We review the interactions between climate and air pollution, with special focus on the projections of air pollution under different future climate scenarios and time horizons, based on a literature review of research articles and reports from the last decade. The assessment focuses on 1) the specific impacts of climate change on air pollution and natural particle and precursor emissions in Europe in the near future (2030), by mid-century (2050) and by end of the century (2100), 2) impacts on air pollution due to changes in emissions vs. changes in climate, 3) feedbacks from air pollution on climate, 4) impacts of climate change on wildland fires and air pollutant levels, and 5) the role of adaptation and mitigation policies on climate change and air pollution. Available literature to a large extent suggests that ozone concentrations will likely increase in the second half of the century by up to 9 ppb [−4 + 9.3], while in the first half of the century, changes are much smaller and are up to ±1.5 ppb. These changes are mainly attributed to increased temperatures and emissions of biogenic volatile organic compounds, but also depends on the models and scenarios used in these studies. On the other hand, the predicted changes in particle concentrations and chemical composition are uncertain and much smaller. Similar to ozone, larger changes in the particle concentrations are projected in the second half of the century. The main conclusion from this review is that the estimated changes in pollutant levels in the future vary significantly depending on the applied model systems, as well as the different emission or meteorological scenarios used in the different studies. Nevertheless, studies generally agree on the overall trend of the changes in pollutant levels due to climate change, in particular in the second half of the century.
Environmental performance and financial performance during COVID-19 outbreak: Insight from Chinese firms
Authors: Kaakeh Mohamad , Gokmenoglu Korhan K.
Published: September 2022

The global pressure to reduce carbon emissions on high-carbon-emitting economies has intensified significantly in recent years. However, these efforts’ effect on the firm’s financial performance (FP) has been a major concern. This research investigates the relationship between environmental performance (EP) and FP of Chinese firms considering the effect of the COVID-19 outbreak. Data was collected from Refinitiv DataStream and span the period of 2017–2020. In addition to the fixed-effects regression, the novel dynamic panel bootstrap corrected fixed effects and panel corrected standard errors methods were utilized to test the hypotheses. Obtained results revealed two key findings. First, there is weak evidence that higher EP increases firms’ FP. Second, the relationship between EP and FP is positive in times of economic distress, meaning that firms must continue investing in environmentally ethical and sustainable projects during the crisis. Our empirical findings extend the existing literature by showing that even in times of crisis, such as COVID-19, an environmentally friendly business model positively affects the firm’s financial structure. We discuss the policy recommendations implied by our findings for investors, business owners, managers, and officials in the conclusion section.
Revisiting the impact of energy consumption, foreign direct investment, and geopolitical risk on CO2 emissions: Comparing developed and developing countries
Authors: Ma Wei , Nasriddinov Fazliddin , Haseeb Mohammad , Ray Samrat , Kamal Mustafa , Khalid Noreen , Ur Rehman Masood
Published: September 2022

A growing body of literature probes the impact of geopolitical risk (GPR) on CO2 emissions. However, no study compares the findings in the case of developed and developing countries. Hence, this study aims to probe the impact of GPR on CO2 emissions for selected developed and developing countries while controlling for energy consumption, foreign direct investment, and economic growth. For this purpose, we make use of a panel dataset covering the period 1990–2020. In the long-run, we report that the Environmental Kuznets Curve hypothesis exists for developing countries. Next, the pollution haven hypothesis is validated for the developed countries in the long-run. Also, GPR escalates emissions for developed and developing countries in the long-run. In the short-run, the Environmental Kuznets Curve and pollution haven hypothesis are found invalid. Moreover, in the short-run, GPR impedes emissions in both developed and developing countries. Further, energy consumption upsurges emissions across all samples (i.e., either developed or developing countries) in either its short- or long-run. The heterogeneous findings across the long- and short-run, for developed and developing countries, propose to formulate unalike policies for countries with different levels of income.
Nexus between trade and environmental quality in sub-saharan Africa: Evidence from panel GMM
Authors: Andriamahery Anselme , Danarson Jules Harris , Qamruzzaman Md
Published: September 2022

Environmental sustainability is a burning fact worldwide, especially in developing nations. Equitable economic development, environmental protection, energy efficiency and security have been placed at the apex of economic discussant and policy formulation. This paper establishes the relationship between trade and environmental quality in Sub-Saharan Africa (SSA). Following the Environmental Kuznets Curve (EKC) theory, we investigate the existence of an inverted U-shape correlation between income per capita growth and nitrous oxide (N2O), agricultural methane (ACH4), and carbon dioxide (CO2) emissions to ascertain the presence of EKC. We also analyze how trade variables, income per capita growth, energy intensity, foreign direct investment, human capital, and CO2 emissions are related. The results show that trade significantly increases N2O, ACH4, and CO2 emissions for the overall sample of SSA and its income groups [Upper-Middle-Income Countries (UMIC), Lower-Middle-Income Countries (LMIC), and Low-Income Countries (LIC)] using a panel GMM. This paper concludes that reducing emissions is feasible in the future as shown by the existence of the EKC, and trade has a consistently negative impact on the environment in SSA countries, regardless of wealth level. On the policy note, the study suggested that domestic trade liberalization and foreign ownership in the economy play a detrimental role, and thus industrialization has to ensure energy efficiency and energy security.
Cellular, molecular and genomic alterations in the hatchlings of Labeo rohita after exposure to Triclosan
Authors: Sharma Sunil , Dar Owias Iqbal , Andotra Megha , Sharma Simran , Bhagat Ankeet , Thakur Sharad , Kesavan Anup Kumar , Kaur Arvinder
Published: September 2022

Triclosan 5-chloro-2-(2, 4-dichlorophenoxy) phenol (TCS) is widely used as a biocide in human and veterinary medicines, personal care products and household articles. To obtain biomarkers for the acute stress of Triclosan, the hatchlings of Labeo rohita were exposed for 96 h to 0.06, 0.067 and 0.097 mg/L TCS. Morphological deformities, cell viability, frequency of micronucleated and aberrant cells, transcriptomic and biomolecular alterations were recorded after exposure and a depuration period of 10 days. The exposed hatchlings had a pointed head, curved trunk, lean body, deformed caudal fin, haemorrhage, hypopigmentation and tissue degeneration at 0.067 and 0.097 mg/L only. The frequency of viable cells declined but that of necrotic, apoptotic, micronucleated and abnormal cells increased (p ≤ 0.01) in a concentration dependent manner after exposure as well as the depuration period. After recovery, the frequency of viable and micronucleated cells increased, but that of necrotic, apoptotic, and aberrant cells declined in comparison to their respective 96 h values. The mRNA level of HSP47, HSP70, HSc71 and α-tropomyosin increased (p ≤ 0.01), while that of HSP60, HSP90, DHPR, myosin light polypeptide 3, desmin b and lamin b1 declined (p ≤ 0.01) after exposure. Ten days post exposure, a significant increase (p ≤ 0.01) over control was observed in the expression of all the heat shock and cytoskeletal genes and the values (except for HSc71) were higher than the respective 96 h values also. Infrared spectra showed that band area of amide A, amide I, amide II and phospholipids increased significantly (p ≤ 0.01) but peak intensity of lipid, glycogen and nucleic acids decreased after exposure. After recovery, area of the peaks for most of the biomolecules [except lipids (2924–2925, 1455–1457 cm−1) and glycogen (1163–1165 cm−1)] declined significantly over control and 96 h values. Collectively these changes seem to be responsible not only for the onset of paralysis but also for the concentration dependent increase in larval and cellular abnormalities as well as no/sporadic swimming movement in exposed hatchlings. It is evident that HSP60, HSc71, HSP90, α-tropomyosin and DHPR were strongly affected but DHPR can be used as the most sensitive marker for the toxicity of TCS. This is the first study reporting effect of TCS on the selected heat shock and cytoskeletal genes in a single model.
Stems matter: Xylem physiological limits are an accessible and critical improvement to models of plant gas exchange in deep time
Authors: Matthaeus William J. , Montañez Isabel P. , McElwain Jennifer C. , Wilson Jonathan P. , White Joseph D.
Published: September 2022

The evolution of woody stems approximately 400 mya (middle Paleozoic) facilitated the expansion of plants and has likely affected carbon and water budgets across much of the terrestrial surface since that time. Stems are a carbon cost/sink and limit water transport from soil to leaves as it must pass through specialized xylem tissue. While leaf fossils have provided a wealth of quantitative data, including estimates of plant water fluxes utilizing biophysically based models, fossil-informed models integrating stem and leaf physiology are lacking. Integrated stem-leaf physiology may distinguish successors to ecological catastrophes like the end of the Late Paleozoic Ice Age (LPIA). The documented collapse of LPIA tropical forests provides an opportunity to assess the importance of woody stems as a key to understanding differences in survivorship among common plant taxa from the Carboniferous to the Permian. Here, we present an analysis of the limits to leaf water supply and plant function for Paleozoic forest plant types due to (1) cavitation-induced embolism and xylem blockage and (2) insufficient sapwood water transport capacity.—collectively defined here as sapwood dysfunction. We first present a modified ecosystem process model (Paleo-BGC+) that includes sapwood dysfunction. Paleo-BGC + is parameterized using measurements obtainable from fossil xylem and therefore applicable to both modern and ancient ecosystems. We then assess the effect of sapwood dysfunction on ecosystem processes based on previously published fossil leaf measurements and a new fossil xylem dataset for plant types present in the Late Paleozoic. Using daily meteorology from a GCM of the late Carboniferous (GENESIS v3) under a Glacial (low-CO2) and an Inter-glacial (high-CO2) scenario, we found that simulated sapwood dysfunction slowed plant water use and reduced carbon storage. This inhibition occurred particularly in plants with high maximum stomatal conductance and high stem vulnerability to embolism. Coincidentally, plants with these traits were predominantly reduced or missing from the fossil record from the Carboniferous to the Permian. Integrating stem and leaf physiology may improve the fidelity of model representations of soil-to-atmosphere water transport through plants, simulations of long-term climate phenomena like the LPIA, and ecosystem projections under future climate change.
Anti-proliferative and pro-apoptotic effects of curcumin on skin cutaneous melanoma: Bioinformatics analysis and in vitro experimental studies
Authors: Li Long , Lu Shuwen , Ma Chao
Published: September 2022

Objective: To reveal the potential mechanisms of curcumin for the treatment of skin cutaneous melanoma (SKCM) and its identify novel prognostic biomarkers.

Methods: We searched the Cancer Genome Atlas and Traditional Chinese Medicine Systems Pharmacology database for the data on SKCM and curcumin. We conducted data analysis using R and online tools. The propagation and migration of SKCM cells were assessed with CCK-8 and scratch wound assays, respectively. We assessed apoptosis by TUNEL assay and western blot.

Results: The survival analysis revealed that the mRNA expressions of DPYD, DPYS, LYN, PRKCQ, and TLR1 were significantly related to a favorable overall survival in SKCM patients. Additionally, the mRNA expression level of DPYD was associated with GPI, LYN, PCSK9, PRKCQ, and TLR1 mRNAs. GSEA results showed that the prognostic hub genes were augmented with ultraviolet, apoptosis, and metastasis. Curcumin expressed proliferation and migration of SK-MEL-1 cells (p < 0.05), and induced apoptosis (p < 0.05) significantly.

Conclusion: Curcumin may have potential therapeutic effects in SKCM by inhibiting cell proliferation and migration and inducing apoptosis by regulating oxygen-related signaling pathways. The hub genes might be identified as novel biomarkers for SKCM.
The prognostic impact of previously infectious complications on allogeneic hematopoietic stem cell transplantation for patients with severe aplastic anemia: A single-center, retrospective study
Authors: Zhang Yuanfeng , Chen Xin , Yang Donglin , Pang Aiming , Zhang Rongli , Ma Qiaoling , Zhai Weihua , He Yi , Wei Jialin , Jiang Erlie , Han Mingzhe , Feng Sizhou
Published: September 2022

Whether infections before transplantation impair the survival of patients with severe aplastic anemia (SAA) remains unclear. The aim of this retrospective cohort analysis was to compare survival between patients with SAA who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with infection (n=66) and patients without infection (n=189) from one medical center. There were no differences in baseline characteristics, except that more patients in the infection group were diagnosed with VSAA (59.09% vs. 30.69%, P<0.001), and their grafts were more peripheral blood stem cells (89.39% vs. 76.72%, P=0.042). In addition, the percentage of patients with multidrug-resistant organism colonization or infection in the infection group was larger (16.7% vs. 0.5%, P<0.001). The median days of engraftment were similar between the two groups; however, the 28-day engraftment rates of neutrophils and platelets were lower in the infection group. No differences were observed in terms of grades II–IV acute graft-versus-host disease (aGVHD) (P=0.418), grades III–IV aGVHD (P=0.075), mild to severe chronic GVHD (cGVHD) (P=0.899), and moderate to severe cGVHD (P=0.342). Patients in the infection group had more bloodstream infections before engraftment (28.8% vs. 15.3%, P=0.016), and the primary cause of death was infection instead of aGVHD in contrast to patients without infection (16.7% vs. 4.2%, P=0.002). Finally, the estimated overall survival (OS), failure-free survival (FFS), and GVHD-free FFS at 5 years were 63% (95% CI, 51–78), 60% (95% CI, 47–74), and 55% (95% CI, 43–70) in patients with infection before transplantation versus 86% (95% CI, 81–92) (P<0.001), 82% (95% CI, 76–88) (P<0.001), and 75% (95% CI, 69–82) (P=0.003) in patients without infection before transplantation, respectively. Multivariate analysis identified haploidentical HSCT and pre-HSCT anti-infection response, defined as partial remission (PR) or stable disease (SD), as adverse factors of OS and FFS. In conclusion, our study demonstrated that SAA patients with infection defined as PR or SD but not complete remission before allo-HSCT showed inferior survival compared with patients without infection. Therefore, more attention should be paid to prophylaxis and complete control of infectious complications before transplantation among SAA patients.
How far are the new wave of mRNA drugs from us? mRNA product current perspective and future development
Authors: Duan Qiongyu , Hu Tianyu , Zhu Qiuxia , Jin Xueying , Chi Feng , Chen Xiaodong
Published: September 2022

mRNA products are therapies that are regulated from the post-transcriptional, pre-translational stage of a gene and act upstream of protein synthesis. Compared with traditional small molecule drugs and antibody drugs, mRNA drugs had the advantages of simple design, short development cycle, strong target specificity, wide therapeutic field, and long-lasting effect. mRNA drugs were now widely used in the treatment of genetic diseases, tumors, and viral infections, and are expected to become the third major class of drugs after small molecule drugs and antibody drugs. The delivery system technology was the key to ensuring the efficacy and safety of mRNA drugs, which plays an important role in protecting RNA structure, enhancing targeting ability, reducing the dose of drug delivery, and reducing toxic side effects. Lipid nanoparticles (LNP) were the most common delivery system for mRNA drugs. In recent years, mRNA drugs have seen rapid development, with the number of drugs on the market increasing each year. The success of commercializing mRNA vaccines has driven a wave of nucleic acid drug development. mRNA drugs were clinically used in genetic diseases, oncology, and infectious diseases worldwide, while domestic mRNA clinical development was focused on COVID-19 vaccines, with more scope for future indication expansion.
Case report: Understanding the impact of persistent tissue-localization of SARS-CoV-2 on immune response activity via spatial transcriptomic analysis of two cancer patients with COVID-19 co-morbidity
Authors: Lau Mai Chan , Yi Yang , Goh Denise , Cheung Chun Chau Lawrence , Tan Benedict , Lim Jeffrey Chun Tatt , Joseph Craig Ryan , Wee Felicia , Lee Justina Nadia , Lim Xinru , Lim Chun Jye , Leow Wei Qiang , Lee Jing Yi , Ng Cedric Chuan Young , Bashiri Hamed , Cheow Peng Chung , Chan Chun Yip , Koh Ye Xin , Tan Thuan Tong , Kalimuddin Shirin , Tai Wai Meng David , Ng Jia Lin , Low Jenny Guek-Hong , Lim Tony Kiat Hon , Liu Jin , Yeong Joe Poh Sheng
Published: September 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected half a billion people, including vulnerable populations such as cancer patients. While increasing evidence supports the persistence of SARS-CoV-2 months after a negative nasopharyngeal swab test, the effects on long-term immune memory and cancer treatment are unclear. In this report, we examined post-COVID-19 tissue-localized immune responses in a hepatocellular carcinoma (HCC) patient and a colorectal cancer (CRC) patient. Using spatial whole-transcriptomic analysis, we demonstrated spatial profiles consistent with a lymphocyte-associated SARS-CoV-2 response (based on two public COVID-19 gene sets) in the tumors and adjacent normal tissues, despite intra-tumor heterogeneity. The use of RNAscope and multiplex immunohistochemistry revealed that the spatial localization of B cells was significantly associated with lymphocyte-associated SARS-CoV-2 responses within the spatial transcriptomic (ST) niches showing the highest levels of virus. Furthermore, single-cell RNA sequencing data obtained from previous (CRC) or new (HCC) ex vivo stimulation experiments showed that patient-specific SARS-CoV-2 memory B cells were the main contributors to this positive association. Finally, we evaluated the spatial associations between SARS-CoV-2-induced immunological effects and immunotherapy-related anti-tumor immune responses. Immuno-predictive scores (IMPRES) revealed consistent positive spatial correlations between T cells/cytotoxic lymphocytes and the predicted immune checkpoint blockade (ICB) response, particularly in the HCC tissues. However, the positive spatial correlation between B cells and IMPRES score was restricted to the high-virus ST niche. In addition, tumor immune dysfunction and exclusion (TIDE) analysis revealed marked T cell dysfunction and inflammation, alongside low T cell exclusion and M2 tumor-associated macrophage infiltration. Our results provide in situ evidence of SARS-CoV-2-generated persistent immunological memory, which could not only provide tissue protection against reinfection but may also modulate the tumor microenvironment, favoring ICB responsiveness. As the number of cancer patients with COVID-19 comorbidity continues to rise, improved understanding of the long-term immune response induced by SARS-CoV-2 and its impact on cancer treatment is much needed.
Regulation of T-independent B-cell responses by microRNA-146a
Authors: King Jennifer K. , Tran Tiffany M. , Paing May H. , Yin Yuxin , Jaiswal Amit K. , Tso Ching-Hsuan , Roy Koushik , Casero David , Rao Dinesh S.
Published: September 2022

The microRNA, miR-146a, is a negative feedback regulator of the central immune transcription factor, nuclear factor kappa B (NFkB). MiR-146a plays important roles in the immune system, and miR-146a deficient mice show a complex phenotype with features of chronic inflammation and autoimmune disease. In this study, we examined the role of miR-146a in extrafollicular B-cell responses, finding that miR-146a suppresses cellular responses in vivo and in vitro. Gene expression profiling revealed that miR-146a-deficient B-cells showed upregulation of interferon pathway genes, including Traf6, a known miR-146a target. We next interrogated the role of TRAF6 in these B-cell responses, finding that TRAF6 is required for proliferation by genetic and pharmacologic inhibition. Together, our findings demonstrate a novel role for miR-146a and TRAF6 in the extrafollicular B-cell responses, which have recently been tied to autoimmune disease pathogenesis. Our work highlights the pathogenetic role of miR-146a and the potential of pharmacologic inhibition of TRAF6 in autoimmune diseases in which miR-146a is deregulated.
Mucosal nanobody IgA as inhalable and affordable prophylactic and therapeutic treatment against SARS-CoV-2 and emerging variants
Authors: Li Qi , Humphries Fiachra , Girardin Roxie C. , Wallace Aaron , Ejemel Monir , Amcheslavsky Alla , McMahon Conor T. , Schiller Zachary A. , Ma Zepei , Cruz John , Dupuis Alan P. , Payne Anne F. , Maryam Arooma , Yilmaz Nese Kurt , McDonough Kathleen A. , Pierce Brian G. , Schiffer Celia A. , Kruse Andrew C. , Klempner Mark S. , Cavacini Lisa A. , Fitzgerald Katherine A. , Wang Yang
Published: September 2022

Anti-COVID antibody therapeutics have been developed but not widely used due to their high cost and escape of neutralization from the emerging variants. Here, we describe the development of VHH-IgA1.1, a nanobody IgA fusion molecule as an inhalable, affordable and less invasive prophylactic and therapeutic treatment against SARS-CoV-2 Omicron variants. VHH-IgA1.1 recognizes a conserved epitope of SARS-CoV-2 spike protein Receptor Binding Domain (RBD) and potently neutralizes major global SARS-CoV-2 variants of concern (VOC) including the Omicron variant and its sub lineages BA.1.1, BA.2 and BA.2.12.1. VHH-IgA1.1 is also much more potent against Omicron variants as compared to an IgG Fc fusion construct, demonstrating the importance of IgA mediated mucosal protection for Omicron infection. Intranasal administration of VHH-IgA1.1 prior to or after challenge conferred significant protection from severe respiratory disease in K18-ACE2 transgenic mice infected with SARS-CoV-2 VOC. More importantly, for cost-effective production, VHH-IgA1.1 produced in Pichia pastoris had comparable potency to mammalian produced antibodies. Our study demonstrates that intranasal administration of affordably produced VHH-IgA fusion protein provides effective mucosal immunity against infection of SARS-CoV-2 including emerging variants.
Treatment of aggressive T-cell lymphoma/leukemia with anti-CD4 CAR T cells
Authors: Feng Jia , Xu Haichan , Cinquina Andrew , Wu Zehua , Zhang Wenli , Sun Lihua , Chen Qi , Tian Lei , Song Le , Pinz Kevin G. , Wada Masayuki , Jiang Xun , Hanes William M. , Ma Yupo , Zhang Hongyu
Published: September 2022

T-cell lymphomas are aggressive lymphomas that often resist current therapy options or present with relapsed disease, making the development of more effective treatment regimens clinically important. Previously, we have shown that CD4 CAR can effectively target T-cell malignancies in preclinical studies. As IL-15 has been shown to strengthen the anti-tumor response, we have modified CD4 CAR to secrete an IL-15/IL-15sushi complex. These CD4-IL15/IL15sushi CAR T cells and NK92 cells efficiently eliminated CD4+ leukemic cell lines in co-culture assays. Additionally, CD4-IL15/IL15sushi CAR out-performed CD4 CAR in in vivo models, demonstrating a benefit to IL-15/IL-15sushi inclusion. In a Phase I clinical trial, CD4-IL15/IL15sushi CAR T cells were tested for safety in three patients with different T-cell lymphomas. Infusion of CD4-IL15/IL15sushi CAR T cells was well-tolerated by the patients without significant adverse effects and led to the remission of their lymphomas. Additionally, infusion led to the depletion of CD4+ Treg cells and expansion of CD3+CD8+ T cells and NK cells. These results suggest that CD4-IL15/IL15sushi CAR T cells may be a safe and effective treatment for patients with relapsed or refractory T-cell lymphomas, where new treatment options are needed.
Aquaporins1 and 3 in the tissues of Paramisgurnus dabryanus and their expression profiles in response to ammonia and drought
Authors: Huang Mei , Zhang Lin-Jiang , Wu Meng-Xiao , Peng Gao-Feng , Zhang Yun-Long
Published: September 2022

Aquaporins (Aqp)1 and Aqp3 are the representatives of two types of aquaporins (classical aquaporin and aquaglyceroporin) and have been proven to potentially facilitate ammonia detoxification in air-breathing fishes. Paramisgurnus dabryanus is one of East Asia’s most important commercially farmed species and can breathe air directly through its hindgut. Besides, excellent ammonia tolerance was reported in this species. However, the mechanisms of its tolerance of high ammonia are still unclear. To explore the physiological roles of Aqp1 and Aqp3 in Paramisgurnus dabryanus, we detected the expression pattern of these two Aqps in several tissues and their transcriptional changes in response to different levels (30, and 70 mmol L-1 NH4Cl) and periods (0, 12, 48, and 96 h) of ammonia exposure and different periods (0, 12, 48, and 96 h) of drought stress. The aqp1 mRNA showed a high abundance in the brain and the osmoregulatory tissues, such as the intestine and kidney. While aqp3 was mainly expressed in the epithelium of skin and gills that were directly exposed to the environment. The expression level of aqp3 in gills was more responsive than aqp1 to ammonia challenges, although both of them were up-regulated. Considering the wide difference between aqp1 and aqp3 in the skin, aqp3 increased significantly after 12 h of air exposure. The changes of the two aqps in the intestine of P. dabryanus were relatively stable after ammonia stress. After drought stress, intestinal aqp1 increased significantly, while aqp3 decreased. Combined with the effects of tissue location and environmental stress on Aqps, it was suggested that Aqp1 was mainly involved in osmotic regulation, providing water as raw material for body metabolism. Accordingly, our results suggest that Aqp3 has the positive function of assisting ammonia transportation and epidermal moisturizing.
Impact of Ionic Liquids on the (bio)degradability of Poly(butylene succinate)/Poly(lactic acid) blends
Authors: Delamarche Emma , Mattlet Agnès , Livi Sébastien , Gérard Jean-François , Bayard Rémy , Massardier Valérie
Published: September 2022

Bio-based and (bio)degradable polymers constitute an important material innovation because they reduce the amount of waste materials inducing persistent microplastics and can offer similar benefits to conventional polymer materials. Poly(butylene succinate) and poly(lactic acid) blends exhibit interesting properties and can be possible alternatives to some traditional polymers. Some of their properties can be tailored by adding small proportions of ionic liquids (IL) that can act as interfacial agents between PBS and PLA. In our study, samples formulated with ionic liquids display a broader morphology with thermal properties close to the PBS/PLA reference, whereas Young’s modulus is lowered in the presence of one of the IL studied. Nevertheless, the blends have a rather different ability to (bio)degrade. Indeed, disintegration experiments show that PBS/PLA/IL exhibit higher weight losses and faster fragmentation. DSC thermograms display an important decrease of PLA melting temperature after composting experiment, indicating that PLA phases are affected the most by degradation at 58°C. Our study shows that elaborating polymer materials, for which degradation processes are preferentially located in a “predegraded” dispersed phase, can be considered as a way to speed up macroscopic (bio)degradation. In the present work, morphologies, mechanical properties as well as (bio)degradability can be tailored by adding a small amount of ionic liquids.
A review on mechanism and application of functional coatings for overhead transmission lines
Authors: Tao Bo , Cheng Li , Wang Jiuyi , Zhang Xinlong , Liao Ruijin
Published: September 2022

Overhead transmission line is the main method of power transmission. Conductors, insulators, and towers are the primary electrical equipment of overhead transmission lines. Due to overhead transmission lines work in the natural environment, problems such as icing, corona discharge, contamination deposition, and corrosion will arise. As a result, some accidents may occur, which cause enormous economic losses. The above problems can be solved by coating functional coatings with superhydrophobic, semiconductive, anti-corrosion, and other characteristics on electrical equipment, which has the advantages of low cost and high efficiency. Therefore, functional coatings have become a research hotspot in the field of external insulation in recent years. In view of the various problems of different electrical equipment in overhead transmission lines, distinctive solutions need to be adopted, so this review classifies the coatings according to the usage scenarios and functions. In each category, first briefly outlines the causes of the electrical equipment problem, then introduces the mechanism of using this type of functional coating to solve the problem, next summarizes the development and application status of this type of coating, after summarizes the limitations of this coating, and finally provides a summary of the key issues in the research of functional coatings and gives an outlook on potential future research directions. This review intends to provide readers with a comprehensive overview of the performance principles and current application status of functional coatings for overhead transmission lines.
Pancreatic family history does not predict disease progression but connotes alcohol consumption in adolescents and young adults with acute pancreatitis: Analysis of an international cohort of 2,335 patients
Authors: Juhász Márk Félix , Farkas Nelli , Szentesi Andrea , Wedrychowicz Andrzej , Nita Andreia Florina , Lásztity Natália , Tészás Alexandra , Tokodi István , Vincze Áron , Eross Bálint , Izbéki Ferenc , Czakó László , Papp Mária , Hegyi Péter , Párniczky Andrea
Published: September 2022

Background

In pediatric acute pancreatitis (AP), a family history of pancreatic diseases is prognostic for earlier onset of recurrent AP (ARP) and chronic pancreatitis (CP). No evidence supports the same association in adult-onset pancreatitis. Age-specific reasons for familial aggregation are also unclear. We aimed to examine the prognostic role of pancreatic family history for ARP/CP and observe possible underlying mechanisms.

Methods

We conducted a secondary analysis of the Hungarian Pancreatic Study Group’s (HPSG) multicenter, international, prospective registry of patients with AP, both children and adults. We compared the positive family history and the negative family history of pancreatic diseases, in different age groups, and analyzed trends of accompanying factors. Chi-square and Fisher exact tests were used.

Results

We found a higher rate of ARP/CP in the positive pancreatic family history group (33.7 vs. 25.9%, p = 0.018), peaking at 6–17 years. Idiopathic AP peaked in childhood in the positive family history group (75% 0–5 years) and was consistently 20–35% in the negative group. A higher rate of alcohol consumption/smoking was found in the positive groups at 12–17 years (62.5 vs. 15.8%, p = 0.013) and 18–29 years (90.9 vs. 58.1%, p = 0.049). The prevalence of diabetes and hyperlipidemia steadily rose with age in both groups.

Conclusion

Positive family history most likely signifies genetic background in early childhood. During adolescence and early adulthood, alcohol consumption and smoking emerge—clinicians should be aware and turn to intervention in such cases. Contrary to current viewpoints, positive pancreatic family history is not a prognostic factor for ARP and CP in adults, so it should not be regarded that way.