bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-investigation of the sector collapse timing of Usu volcano, Japan, inferred from reworked ash deposits caused by debris avalanche
Authors: Nakagawa Mitsuhiro , Matsumoto Akiko , Yoshizawa Mitsuki
Published: September 2022

It is essential to establish the timing of past sector collapse events at a volcanic edifice to evaluate not only the evolution of the volcanic system but also potential volcanic hazards. This can be done by determining the age of the collapse-generated debris avalanche deposits. However, without evidence of an associated magmatic eruption, it is impossible to recognize juvenile materials in these deposits. Thus, it is usually difficult to determine the precise age of sector collapse. Usu is a post-caldera volcano of the Toya Caldera (Hokkaido, Japan) and has been constructed since ca. 19–18 ka on top of the caldera-forming Toya pyroclastic flow deposits (Tpfl deposit: 106 ka). A sector collapse occurred after the formation of a stratovolcano edifice and produced the Zenkoji debris avalanche (ZDA) deposit with reported ages ranging from >20 to 6 ka. We investigated the tephrostratigraphy preserved in the soil above the ZDA deposit and in the surrounding area and recognized fine ash fall deposits at two locations, above and east of the ZDA deposit. The glass shards within these deposits were correlated with several tephra layers with the majority being derived from Tpfl deposits. Thus, these ash deposits should be considered reworked tephra. A considerable number of hummocks in the ZDA deposit were also composed of deformed and fragmented Tpfl deposits, which suggests that the ZDA bulldozed and partially incorporated the Tpfl deposit on the flank of the volcano. Deformation and fragmentation of the non-welded soft silicic Tpfl deposit during the transport and emplacement of the ZDA produced an accompanying ash cloud, which deposited the observed glassy, fine, ash fall units. Radiocarbon dating of soil samples directly below and above the reworked ash deposits allowed dating the sector collapse to ca. 8 ka. This age is much younger than previously proposed results. Based on our findings, the transport and emplacement mechanism of the sector collapse should be revised. Our study shows that reworked ash layers caused by the flow of a debris avalanche can be used as an indicator of the timing of a sector collapse of the volcano.
Critical characteristics of an airlift pump for dredging
Authors: Hu Dong , Guo Jingzhi , Deng Ling , Yang Fengling
Published: September 2022

There are many factors that affect an airlift pump for dredging. In actual applications, if these factors cannot be fully considered, the performance of the airlift pump will be reduced. In view of this, based on the critical model of the water–solid two-phase flow and the gas holding model, a critical model of the gas–water–solid three-phase flow is proposed. The research results show that, compared with the two-phase flow, the critical water flow rate for lifting solids in the three-phase flow is always smaller. Therefore, it is necessary to consider the static chip retention force so that the critical model in the two-phase flow can be modified. It shows that the static chip retention effect is opposite to the “start” of the particle. Not only that, but also discussed are the critical conditions of solid particles or vertical lifting water from a practical point of view. The results show that solid particles will not affect the critical air flow rate of pumping water. However, the size and location of the solid particles affect the critical air flow rate.
From pre- and in-service teachers’ asymmetric backgrounds to equal co-teaching: Investigation of a professional learning model
Authors: Kervinen Anttoni , Portaankorva-Koivisto Päivi , Kesler Merike , Kaasinen Arja , Juuti Kalle , Uitto Anna
Published: September 2022

The existing co-teaching practices in teachers’ professional learning emphasize collaboration between pre-service and in-service teachers. Although this collaboration is usually defined by a mentor–student relationship with asymmetric power relations, successful co-teaching practices in schools are considered to involve parity, resulting in mutual learning for all involved parties. In this study, we designed a model for teachers’ professional learning in which pre- and in-service teachers collaborate and have shared goals, with the aim of equal responsibilities for planning and implementing instruction, despite the teachers’ diverse backgrounds. During the 4 years of piloting and developing the model in the Finnish teacher education context, we investigated how the participants reflected on the co-teaching process. We analyzed data from collaborative reflection sessions to identify the challenges and benefits of this untypical form of collaboration. The findings showed that asymmetric backgrounds may cause challenges, but that if these are overcome, they can also create opportunities for valuable co-teaching experiences for all the participants. Helping the participants initiate the co-teaching process and take different roles appeared to be essential for a successful process. We discuss the findings regarding the development of co-teaching practices in teacher education and in schools.
Energy-efficient neural network design using memristive MAC unit
Authors: Yu Shengqi , Bunnam Thanasin , Triamlumlerd Sirichai , Pracha Manoch , Xia Fei , Shafik Rishad , Yakovlev Alex
Published: September 2022

Artificial intelligence applications implemented with neural networks require extensive arithmetic capabilities through multiply-accumulate (MAC) units. Traditional designs based on voltage-mode circuits feature complex logic chains for such purposes as carry processing. Additionally, as a separate memory block is used (e.g., in a von Neumann architecture), data movements incur on-chip communication bottlenecks. Furthermore, conventional multipliers have both operands encoded in the same physical quantity, which is either low cost to update or low cost to hold, but not both. This may be significant for low-energy edge operations. In this paper, we propose and present a mixed-signal multiply-accumulate unit design with in-memory computing to improve both latency and energy. This design is based on a single-bit multiplication cell consisting of a number of memristors and a single transistor switch (1TxM), arranged in a crossbar structure implementing the long-multiplication algorithm. The key innovation is that one of the operands is encoded in easy to update voltage and the other is encoded in non-volatile memristor conductance. This targets operations such as machine learning which feature asymmetric requirements for operand updates. Ohm’s Law and KCL take care of the multiplication in analog. When implemented as part of a NN, the MAC unit incorporates a current to digital stage to produce multi-bit voltage-mode output, in the same format as the input. The computation latency consists of memory writing and result encoding operations, with the Ohm’s Law and KCL operations contributing negligible delay. When compared with other memristor-based multipliers, the proposed work shows an order of magnitude of latency improvement in 4-bit implementations partly because of the Ohm’s Law and KCL time savings and partly because of the short writing operations for the frequently updated operand represented by voltages. In addition, the energy consumption per multiplication cycle of the proposed work is shown to improve by 74%–99% in corner cases. To investigate the usefulness of this MAC design in machine learning applications, its input/output relationships is characterized using multi-layer perceptrons to classify the well-known hand-writing digit dataset MNIST. This case study implements a quantization-aware training and includes the non-ideal effect of our MAC unit to allow the NN to learn and preserve its high accuracy. The simulation results show the NN using the proposed MAC unit yields an accuracy of 93%, which is only 1% lower than its baseline.
Carbon market volatility analysis based on structural breaks: Evidence from EU-ETS and China
Authors: Yu Haixu , Wang He , Liang Chuanyu , Liu Zhaohua , Wang Susheng
Published: September 2022

In recent years, carbon market transactions have become more active. The number of countries participating in carbon market regulation is increasing, and the carbon market’s overall turnover continues to grow. It is important to study the features of carbon allowance price volatility for the stable development of the carbon market. This paper constructs a modified ICSS-GARCH model to analyze the volatility of carbon price returns and the dynamic characteristics of price fluctuations in the emissions trading system of the European Union (EU-ETS) and the Chinese carbon pilot markets in Hubei. The results show that fluctuations in carbon price returns have a leverage effect and that the impact of negative news on the market is stronger than that of positive news. The international climate and energy conferences, abnormal changes in traditional energy prices, and global public health emergencies all affect volatility and cause shocks to the carbon trading market. The modified ICSS-GARCH model with structural breaks can reduce the pseudovolatility of the return series to a certain extent and can improve the accuracy of the model. This research can give policymakers some implications about how to develop the carbon market and help market participants control the risks of fluctuations in carbon allowances. Regulators should enhance carbon price monitoring and focus on short-term shocks in the carbon market to reduce trading risks. The Chinese carbon market should strengthen the system design and develop carbon financial derivatives.
Socio-psychological antecedents of pro-environmental intentions and behaviors among Iranian rural women: An integrative framework
Authors: Karimi Saeid , Mohammadimehr Sahra
Published: September 2022

The main purpose of this research was to identify factors influencing Iranian rural women’s pro-environmental intentions and behaviors by integrating the Theory of Planned Behavior and the Value-Belief-Norm theory into a theoretical framework. The model was tested using the partial least squares structural equation modeling (PLS-SEM) on data collected through a questionnaire survey from 332 Iranian rural women. The results indicated that the integrated model could account for 67 and 29 percent of the variance in pro-environmental intentions and behaviors, respectively. Perceived behavioral control was the strongest antecedent of pro-environmental behaviors, followed by intention. Perceived behavioral control was also the strongest direct determinant of intentions, followed by subjective norms and attitudes. In addition, the results revealed that awareness of consequences was indirectly and significantly related to intention through subjective norms, attitudes, and perceived behavioral control. Overall, the results provided a strong support for the integrative model and yielded more insight into socio-psychological factors influencing Iranian rural women’s pro-environmental intentions and behaviors. The empirical findings of this study can be used by researchers, policymakers, and governments to develop and implement effective programs to promote sustainable behaviors among rural women.
Comparative analysis of the neutralizing activity against SARS-CoV-2 Wuhan-Hu-1 strain and variants of concern: Performance evaluation of a pseudovirus-based neutralization assay
Authors: D’Apice Luciana , Trovato Maria , Gramigna Giulia , Colavita Francesca , Francalancia Massimo , Matusali Giulia , Meschi Silvia , Lapa Daniele , Bettini Aurora , Mizzoni Klizia , Aurisicchio Luigi , Di Caro Antonino , Castilletti Concetta , De Berardinis Piergiuseppe
Published: September 2022

Objectives

Emergence of new variants of SARS-CoV-2 might affect vaccine efficacy. Therefore, assessing the capacity of sera to neutralize variants of concern (VOCs) in BSL-2 conditions will help evaluating the immune status of population following vaccination or infection.

Methods

Pseudotyped viruses bearing SARS-CoV-2 spike protein from Wuhan-Hu-1/D614G strains (wild type, WT), B.1.617.2 (Delta), or B.1.1.529 (Omicron) VOCs were generated to assess the neutralizing antibodies (nAbs) activity by a pseudovirus-based neutralization assay (PVNA). PVNA performance was assessed in comparison to the micro-neutralization test (MNT) based on live viruses. Sera collected from COVID-19 convalescents and vaccinees receiving mRNA (BNT16b2 or mRNA-1273) or viral vector (AZD1222 or Ad26.COV2.S) vaccines were used to measure nAbs elicited by two-dose BNT16b2, mRNA-1273, AZD1222 or one-dose Ad26.CO2.S, at different times from completed vaccination, ~ 1.5 month and ~ 4-6 months. Sera from pre-pandemic and unvaccinated individuals were analyzed as controls. Neutralizing activity following booster vaccinations against VOCs was also determined.

Results

PVNA titers correlated with the gold standard MNT assay, validating the reliability of PVNA. Sera analyzed late from the second dose showed a reduced neutralization activity compared to sera collected earlier. Ad26.CO2.S vaccination led to very low or absent nAbs. Neutralization of Delta and Omicron BA.1 VOCs showed significant reduction of nAbs respect to WT strain. Importantly, booster doses enhanced Omicron BA.1 nAbs, with persistent levels at 3 months from boosting.

Conclusions

PVNA is a reliable tool for assessing anti-SARS-CoV-2 nAbs helping the establishment of a correlate of protection and the management of vaccination strategies.
The inhibition of warm advection on the southward expansion of sea ice during early winter in the Bering Sea
Authors: Wang Weibo , Su Jie , Jing Chunsheng , Guo Xiaogang
Published: September 2022

Recent observations demonstrate that the Bering Sea exhibits a substantial positive trend of sea ice area increment (ΔSIA, difference in SIA between the current and preceding months) in January contrasted to the considerable negative sea ice area (SIA) trend from 1979 to 2020, and the ΔSIA is unrelated to the local wind field anomaly. To better understand the January ΔSIA variability and its physical characteristics, we explore two distinct empirical orthogonal function (EOF) modes of sea ice concentration increments. EOF1 features a reduction in sea ice concentration (SIC) in the south of St. Lawrence Island. EOF2 is characterized by the rise of SIC surrounding St. Lawrence Island. EOF1 is related to the well-known physical process of December strong poleward heat transport in mixed layer depth. During the southward expansion of sea ice, the multiyear variation of the December SST tendency mostly relies on warm advection in the Bering Sea shelf rather than net air-sea heat flux, and the abnormal northeast wind in December no longer plays the role of a dynamic process dominating the ice area expansion, but generates a stronger poleward heat transport in the Bering Sea shelf to inhibit the southward development of sea ice in the later stage. The two physical processes together result in oceanic poleward heat transport regulating the Bering Sea SIA in competition with atmospheric forcing in early winter. Since PC1 (principal component (PC) time series for EOF1) has a high correlation of -0.76 with the maximum SIA in the Bering Sea, it can be used as the prediction index of the Bering Sea maximum SIA.
Seasonal variations in biochemical and stable isotope compositions of particulate organic matter in two contrasting temperate coastal lagoons of Korea
Authors: Lee Dong-Young , Kwak Jung Hyun , Park Tae Hee , Kang Hee Yoon , Kim Dongyoung , Hwang Sungmin , Park Hyun Je
Published: September 2022

The geomorphology of coastal lagoons has an important effect on the hydrological balance between fresh water and seawater, which exhibit a wide range of salinity from nearly fresh water to hypersaline water. The present study aimed to characterize seasonal biogeochemical properties of suspended particulate organic matter (POM) in response to environmental variability driven by hydrological dynamics in contrasting coastal lagoon systems. We selected two lagoons distinguished by their geomorphological features, a permanently open artificial lagoon (Gyeongpoho) and an intermittently open natural lagoon (Hyangho), analyzed environmental characteristics, and compared the seasonal differences in the biochemical compositions of POM. Variations in temperature and precipitation in both lagoons showed the characteristics of a typical monsoon climate but variation in salinity differed 6.5−35.0 in Gyeongpoho and 1.1−10.8 in Hyangho. A self-organizing map analysis using the environmental data revealed that the spatiotemporal variations in salinity and nutrient concentrations differed significantly between the two lagoon systems, indicating a difference in hydrologic connectivity between lagoons and marine systems. Furthermore, a canonical correlation analysis highlighted that the POM properties differed according to physicochemical factors. The differing environmental conditions may affect the spatial and temporal variations in organic matter composition, resulting in significant differences in the biochemical composition of POM between two lagoon systems. Overall, this information provides insight into the origin and transport process of POM under changing coastal lagoon environments caused by climatic and human activities.
The impact of the COVID-19 pandemic on colorectal and gastric cancer diagnosis, disease stage and mortality
Authors: Abu-Freha Naim , Hizkiya Reut , Abu-Abed Muhammad , Michael Tal , Jacob Binil Mathew , Rouvinov Keren , Schwartz Doron , Reshef Avraham , Netz Uri , Pinsk Ilia , Etzion Ohad
Published: September 2022

Background

Since the outbreak of COVID-19, a significant decline in endoscopic procedures has been observed.

Aims

We investigated the change of incidence, clinical characteristics, disease stage and mortality of patients with gastric cancer (GC) or colorectal cancer (CRC) diagnosed in 2020 compared to the pre-pandemic year 2019.

Methods

Demographic, clinical and laboratory data on all patients diagnosed with GC or CRC at the Soroka University Medical Center were retrospectively collected and compared. Number of cases, time of diagnosis, clinical presentation, staging at diagnosis and mortality rates were compared.

Results

Two hundred sixteen patients were diagnosed with CRC in 2019, whereas only 162 were diagnosed in 2020 (25% reduction), while 36 GC diagnoses were made in 2019 compared to 24 in 2020 (33% reduction). The age-adjusted incidence was calculated to be 24.28 for CRC and 5.0 for GC in 2020 compared to 29.93 and 5.32 in 2019, respectively. CRC patients had a significantly lower rate of rectal bleeding as their presenting symptom in 2020 compared with 2019, 8.1 vs. 19% (p = 0.003), but higher rate of diarrhea as their presenting symptom, 4.3 vs. 1% (p = 0.044). No significant differences regarding other presenting symptoms, comorbidities, surgery or mortality rates were found between the groups diagnosed in 2019 or 2020.

Conclusion

A decrease in GC and CRC incidence was observed during the year 2020; lower rate of rectal bleeding and higher rate of diarrhea as presenting symptoms were noted in 2020, but no significant difference was found regarding other presenting symptoms, disease stage, surgery or mortality.
Genomic characterization of two community-acquired methicillin-resistant Staphylococcus aureus with novel sequence types in Kenya
Authors: Njenga John , Nyasinga Justin , Munshi Zubair , Muraya Angela , Omuse Geoffrey , Ngugi Caroline , Revathi Gunturu
Published: September 2022

Staphylococcus aureus is a clinically important bacteria with high antimicrobial resistance (AMR) challenge globally. The emergence of methicillin-resistant Staphylococcus aureus (MRSA) clones with unique sequence types have been identified in the community showing evidence that the epidemiology of MRSA globally is changing and requires continual surveillance. We utilized whole genome sequencing to characterize two community acquired-MRSA (CA-MRSA) strains isolated from wound swabs from community-onset infections in two health facilities in Kenya. The two strains belonged to multilocus sequence type (MLST) sequence type (ST) 7460, and ST 7635. The resistance genes detected showed that the novel STs are carriers of clinically relevant resistance genes. Linezolid and mupirocin resistance was observed, yet mupirocin is not commonly used in the country. Mutations within resistance genes were also detected and the pathogenicity toward the human host matched various pathogenic global S. aureus families, e.g., S. aureus subsp. aureus USA300. Multidrug efflux transporters, important in antimicrobial resistance including restriction enzymes type I and type IV were detected. Plasmids identified showed similarities with the plasmids in other clinically significant non-staphylococcal species, such as Pseudomonas aeruginosa, Escherichia coli, Morganella morganii, and Enterococcus faecium. Both STs belong to clonal complex 8 (CC8) which is the most successful MRSA clone in Kenya. Spa type t30 to which ST 7635 belongs has not been reported in the country. The results of this study further highlight the need for epidemiological studies to reveal circulating strains and antimicrobial resistance spread between hospitals and the community. The genomic research highlights resistance to anti-staphylococcal broad-spectrum antimicrobials not used frequently in the country, jeopardizing successful MRSA treatment since most health facilities do not perform genotypic resistance tests for routine patient management. Preliminary insights into unidentified STs of CA-MRSA in Kenya show the need for molecular epidemiological surveillance studies to further understand the diversity of S. aureus in Africa.
Relationship between gut microbiota and lymphocyte subsets in Chinese Han patients with spinal cord injury
Authors: Pang Rizhao , Wang Junyu , Xiong Yisong , Liu Jiancheng , Ma Xin , Gou Xiang , He Xin , Cheng Chao , Wang Wenchun , Zheng Jinqi , Sun Mengyuan , Bai Xingang , Bai Ling , Zhang Anren
Published: September 2022

This study is to investigate the changes of lymphocyte subsets and the gut microbiota in Chinese Han patients with spinal cord injury (SCI). We enrolled 23 patients with SCI and 21 healthy controls. Blood and fecal samples were collected. The proportion of lymphocyte subsets was detected by flow cytometry. 16S rDNA sequencing of the V4 region was used to analyze the gut microbiota. The changes of the gut microbiota were analyzed by bioinformatics. Correlation analysis between gut microbiota and lymphocyte subsets was performed. CD4 + cells, CD4 + /CD8 + ratio and CD4 + CD8 + cells in peripheral blood of SCI patients were significantly lower than those of the control group (P < 0.05). There was no significant difference in B cells and CIK cells between the SCI group and the control group. The gut microbiota community diversity index of SCI patients was significantly higher than that of healthy controls. In SCI patients, the relative abundance of Lachnospiraceae (related to lymphocyte subset regulation), Ruminococcaceae (closely related to central nervous system diseases), and Escherichia-Shigella (closely related to intestinal infections) increased significantly, while the butyrate producing bacteria (Fusobacterium) that were beneficial to the gut were dramatically decreased. Correlation analysis showed that the five bacterial genera of SCI patients, including Lachnospiraceae UCG-008, Lachnoclostridium 12, Tyzzerella 3, Eubacterium eligens group, and Rumencocciucg-002, were correlated with T lymphocyte subsets and NK cells. In the SCI group, the flora Prevotella 9, Lachnospiraceae NC2004 group, Veillonella, and Sutterella were positively correlated with B cells. However, Fusobacterium and Akkermansia were negatively correlated with B cells. Moreover, Roseburia and Ruminococcaceae UCG-003 were positively correlated with CIK cells. Our results suggest that the gut microbiota of patients with SCI is associated with lymphocyte subsets. Therefore, it is possible to improve immune dysregulation in SCI patients by modulating gut microbiota, which may serve as a new therapeutic method for SCI.
Unveiling antiplasmodial alkaloids from a cumulative collection of Strychnos extracts by multi-informative molecular networks
Authors: Bonnet Olivier , Beniddir Mehdi A. , Champy Pierre , Degotte Gilles , Mamede Lúcia , Desdemoustier Pauline , Ledoux Allison , Tchinda Alembert Tiabou , Angenot Luc , Frédérich Michel
Published: September 2022

Malaria, a disease known for thousands of years and caused by parasites of the Plasmodium genus, continues to cause many deaths throughout the world today, particularly due to the emergence of parasite resistance to the current therapeutic arsenal. Plants of the Strychnos genus, remarkable due to their multiple traditional uses as well as their alkaloid content, are promising candidates to develop new antimalarial treatments. Indeed, previous research on this plant group has shown promising (≤ 5 µg/ml) or good (between 5 and 15 µg/ml) antiplasmodial activities. Using the chloroquine-sensitive strain of Plasmodium falciparum (3D7), and artemisinin as positive control, a screening of antiplasmodial activities from 43 crude methanolic extracts from 28 species of the Strychnos genus was carried out in three independent assays. A total of 12 extracts had good (6 extracts) or promising (6 extracts) antiplasmodial activities. These results allowed both to confirm known activities but also to detect new ones. These extracts were then analyzed by HPLC-ESI(+)-Q/TOF, and the processed MS/MS data allowed to generate a molecular network in which the antiplasmodial activities were implemented as metadata. The exploration of the molecular network revealed the presence of alkaloids still unknown, and potentially active against malaria, in particular alkaloids close to usambarensine and its derivatives. This study shows that the emergence of molecular networking offers new leads for identifications of alkaloids from the Strychnos genus. The presence of unknown alkaloids potentially active against malaria confirms all the interest to continue in studying the Strychnos genus. Bioassay- and mass-guided fractionations as well as various dereplication tools would allow to identify and characterize these interesting alkaloids further.
Nanocomposite films as electrochemical sensors for detection of catalase activity
Authors: Johnson Dwight , Kim Unyoung , Mobed-Miremadi Maryam
Published: September 2022

Cross-linked hydrogel substrates have garnered attention as they simultaneously enable oxidoreductase reactions in a control volume extended to adsorption of redox capacitors for amplification of electrochemical signals. In this study, the effect of catalase immobilization in mold-casted alginate-based thin films (1 mm × 6 mm × 10 mm) containing multi walled carbon nanotubes (MWCNT) coated with chitosan has been studied via amperometry. The amperometric response was measured as a function of peroxide concentration, at a fixed potential of −0.4 V vs. SPCE in phosphate-buffered saline (pH = 7.4). Results indicate substrate detection is not diffusion-limited by the 100 μm thick chitosan layer, if the cationic polyelectrolyte is in contact with the sensing carbon electrode, and the linear detection of the enzyme absent in solution is enabled by immobilization (R2 = 0.9615). The ferricyanide-mediated biosensor exhibited a sensitivity of 4.55 μA/mM for the optimal formulation at room temperature comparable to other nanomaterial hybrid sensing solution namely amine-functionalized graphene with an average response time of 5 s for the optimal formulation. The suitability of the optimized chitosan-coated alginate slabs nano-environment for co-encapsulation of catalase and carbon nanotubes was confirmed by cyclic voltammetry.
Spike S1 domain interactome in non-pulmonary systems: A role beyond the receptor recognition
Authors: Iacobucci Ilaria , Monaco Vittoria , Canè Luisa , Bibbò Francesca , Cioffi Valentina , Cozzolino Flora , Guarino Alfredo , Zollo Massimo , Monti Maria
Published: September 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which, since 2019 in China, has rapidly become a worldwide pandemic. The aggressiveness and global spread were enhanced by the many SARS-CoV-2 variants that have been isolated up to now. These mutations affect mostly the viral glycoprotein Spike (S), the capsid protein mainly involved in the early stages of viral entry processes, through the recognition of specific receptors on the host cell surface. In particular, the subunit S1 of the Spike glycoprotein contains the Receptor Binding Domain (RBD) and it is responsible for the interaction with the angiotensin-converting enzyme 2 (ACE2). Although ACE2 is the primary Spike host receptor currently studied, it has been demonstrated that SARS-CoV-2 is also able to infect cells expressing low levels of ACE2, indicating that the virus may have alternative receptors on the host cells. The identification of the alternative receptors can better elucidate the pathogenicity and the tropism of SARS-CoV-2. Therefore, we investigated the Spike S1 interactomes, starting from host membrane proteins of non-pulmonary cell lines, such as human kidney (HK-2), normal colon (NCM460D), and colorectal adenocarcinoma (Caco-2). We employed an affinity purification-mass spectrometry (AP-MS) to pull down, from the membrane protein extracts of all cell lines, the protein partners of the recombinant form of the Spike S1 domain. The purified interactors were identified by a shotgun proteomics approach. The lists of S1 potential interacting proteins were then clusterized according to cellular localization, biological processes, and pathways, highlighting new possible S1 intracellular functions, crucial not only for the entrance mechanisms but also for viral replication and propagation processes.
Comparison of methods of isolating extracellular vesicle microRNA from HepG2 cells for High-throughput sequencing
Authors: Xiong Ying-Hui , Fan Xue-Gong , Chen Ya-Yu , Huang Yan , Quan Jun , Yi Pan-Pan , Xiao Mei-Fang , Huang Ze-Bing , Hu Xing-Wang
Published: September 2022

Background: Extracellular vesicles (EVs) were reported to participate in various cellular processes based on the biomolecules, particularly microRNAs. Numerous commercial EVs isolation reagents are available. However, whether these reagents are suitable for separating EVs from the culture medium supernatant supernatant of model cell lines, such as HepG2, and whether the isolated products are suitable for High-throughput sequencing remains unclear.

Methods: We examined three commonly used EVs isolation kits: the ExoQuick-TC exosome precipitation solution (EQ), Total Exosome Isolation from cell culture medium (EI), and exoEasy Maxi Kit (EM), to isolate EVs from HepG2 cell culture medium supernatants. EVs were identified based on marker proteins, particle size measurements, and electron microscopy analysis. The total amounts of microRNA and microRNA High-throughput sequencing data quality from EVs isolated by each kit were compared.

Results: The total amount of EVs’ microRNA isolated from the EI and EM groups were higher than that obtained from the EQ group (EQ/EI: p = 0.036, EI/EM: p = 0.024). High-throughput sequencing data quality evaluation showed that the EI group possessed higher quality than those in the EM group.

Conclusion: For the cell culture medium from HepG2, EVs’ microRNA isolated by EI reagents might be more suitable for High-throughput sequencing applications.
Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world
Authors: Di Cosimo Serena , La Rocca Eliana , Ljevar Silva , De Santis Maria Carmen , Bini Marta , Cappelletti Vera , Valenti Marta , Baili Paolo , de Braud Filippo G. , Folli Secondo , Scaperrotta Gianfranco , Volpi Chiara , Vingiani Andrea , Vernieri Claudio , Verderio Paolo , Miceli Rosalba , Pruneri Giancarlo
Published: September 2022

Background: Previous data, mostly from clinical trials, reported that HER2-low status is associated with low pathological complete response (pCR), and favourable prognosis. Since these findings suggest the existence of an additional breast cancer subtype, we questioned if the predictive/prognostic value of HER2-low was also relevant in the real world.

Methods: Data from non-metastatic breast cancer patients treated with neoadjuvant chemotherapy and surgery (2009–2020) were retrieved from our institutional prospectively-maintained registry. Univariable and multivariable logistic models were implemented to study the association between pCR and baseline HER2 status. Univariable analysis of disease-free survival (DFS) was performed through Kaplan-Meier survival curves and log-rank tests.

Results: Starting from a total of 790 consecutive cases, we identified 444 newly-diagnosed breast cancer patients featuring HER2 immunohistochemistry (IHC) 0 (HER2-0, n = 109), and 1 + or IHC 2+/in situ hybridization negative (HER2-low, n = 335) receiving anthracycline and taxane-based regimens in 88.9% of cases. Most of the patients were diagnosed with stage II (67.3%) and there was no difference of disease presentation according to HER2-status. pCR was attained by 71 (16.0%) patients and was significantly associated with increased DFS (p = 0.031). Compared to HER2-0, HER2-low cases were more likely hormone receptor-positive (81.2% vs. 43.1%, p < 0.001), well-differentiated (47.5% vs. 26.6%, p = 0.001), less proliferative (21.5% vs. 8.3%, p = 0.001) and less responsive to treatment (pCR 11.6% vs. 29.4%, p < 0.0001). There was no difference in DFS according to HER2 status, though hormone-receptor (HR) negative/HER2-low cases tended to have a worse prognosis compared to HR-negative/HER2-0. By pCR achievement, 3-years DFS was 87.5.% (75.1–100%) vs. 71.6% (65.9–77.8%) (p = 0.161) in HER2-low and 89.1% (75.8–100%) vs. 72.1% (59.7–87.0%) (p = 0.092) in HER2-0.

Conclusion: Our real-world data show that HER2-low breast cancer patients represent roughly a half of the cases treated with neoadjuvant therapy, and have poor treatment response. In absence of pCR, HER2-low breast cancer patients have a dismal prognosis, especially when primary tumor hormone receptor status is negative. Studies are therefore needed to define the biology of these tumors for new therapeutic targets and to incorporate HER2-targeting agents in early-stage treatment.
Mind–Body Exercises for Non-motor Symptoms of Patients With Parkinson’s Disease: A Systematic Review and Meta-Analysis
Authors: Wang Kai , Li Kunbin , Zhang Peiming , Ge Shuqi , Wen Xiaopeng , Wu Zhiyuan , Yao Xianli , Jiao Bing , Sun Pingge , Lv Peipei , Lu Liming
Published: September 2022

Objective: This study aimed to systematically evaluate the effects of mind–body exercise on global cognitive function, depression, sleep disorders, fatigue level, and quality of life (QOL) in a Parkinson’s disease (PD) population.

Methods: Total six English and Chinese databases were searched for articles published up to May 2021. Randomized controlled trials (RCTs) evaluating mind–body excises on non-motor symptoms of PD were included. The Cochrane risk of bias tool was used to assess the methodological quality, and we defined high-quality studies as having a low risk of bias in four or more domains. Global cognitive function was considered the primary outcome and was assessed using the Montreal Cognitive Assessment (MoCA). The secondary outcomes included QOL, fatigue, depression, and sleep quality, which were measured using the Parkinson’s Disease Questionnaire (PDQ-39), 16-item Parkinson’s Disease Fatigue Scale (PFS-16), Beck Depression Inventory (BDI), and revised Parkinson’s Disease Sleep Scale (PDSS-2), respectively. Subgroup analyses were conducted for global cognitive function and QOL to assess the optimal treatment measure across the various mind–body exercises.

Results: Fourteen RCTs with 404 patients were finally included in the meta-analysis. Eight (57.14%) studies were of high quality. The pooled results showed that mind–body exercises generally had a significant advantage over the control intervention in improving global cognitive function (MD = 1.68; P = 0.0008). The dose subgroup analysis revealed that the low dose (60–120 min per week) and moderate dose (120–200 min per week) significantly increased MoCA scores compared with the control group (MD = 2.11, P = 0.01; MD = 1.27, P = 0.02, respectively). The duration subgroup analysis indicated a significant difference in the effect of the duration (6–10 and >15 weeks) on increasing MoCA scores compared with the control group (MD = 3.74, P < 0.00001; MD = 1.45, P = 0.01, respectively).

Conclusion: Mind–body exercise may improve global cognitive function, sleep quality, and QOL in the PD population. In addition, low to moderate doses and appropriate durations significantly improved global cognitive function.

Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [CRD42021275522].
Prelimbic Ensembles Mediate Cocaine Seeking After Behavioral Acquisition and Once Rats Are Well-Trained
Authors: Sortman Bo W. , Gobin Christina , Rakela Samantha , Cerci Berk , Warren Brandon L.
Published: September 2022

Substance use disorder (SUD) is a chronic relapsing condition characterized by continued use of drugs despite negative consequences. SUD is thought to involve disordered learning and memory wherein drug-paired cues gain increased salience, and ultimately drive craving and relapse. These types of associations are thought to be encoded within sparsely distributed sets of neurons, called neuronal ensembles, that drive encoded behaviors through synchronous activity of the participant neurons. We have previously found that Fos-expressing neuronal ensembles within the prefrontal cortex are required for well-trained cocaine seeking. However, less is known about how quickly cortical neuronal ensembles form during the initiation of cocaine seeking behavior. Here, we seek to further elucidate the role of Fos-expressing neuronal ensembles within the prelimbic cortex (PL) after the initial acquisition of cocaine self-administration (SA), or, after 10 days of additional SA training (well-trained). We trained Fos-LacZ transgenic rats to lever press for cocaine under an FR1 schedule of reinforcement. Once rats met acquisition criteria for cocaine self-administration, we ablated Fos-expressing neuronal ensembles in the PL using the Daun02 inactivation method, either 1 or 10 days after the rats met the acquisition criteria. Targeted ablation of Fos-expressing neuronal ensembles in the PL attenuated active lever pressing both 1 day and 10 days after rats acquired cocaine self-administration. Together, this suggests that Fos-expressing neuronal ensembles rapidly form in the PL and continue to mediate maintained cocaine seeking behavior.
Reducing intravenous thrombolysis delay in acute ischemic stroke through a quality improvement program in the emergency department
Authors: Yuan Guangxiong , Xia Hong , Xu Jun , Long Chen , Liu Lei , Huang Feng , Zeng Jianping , Yuan Lingqing
Published: September 2022

Objective

This study aims to investigate the effectiveness of a quality improvement program for reducing intravenous thrombolysis (IVT) delay in acute ischemic stroke (AIS).

Materials and methods

We implement a quality improvement program consisting of 10 interventions for reducing IVT delay, including the establishment of an acute stroke team, standardized management of stroke teams, popularization of stroke and its treatment, emergency bypass route (BER), the achievement of computed tomography (CT) priority, no-delay CT interpretation, intravenous thrombolysis on the CT table, payment after treatment, whole recording, and incentive policy. We retrospectively analyzed the clinical time and outcome data of AIS patients treated with IVT in pre-intervention (108 patients) and post-intervention groups (598 patients), and further compared the differences between the non-emergency bypass route (NBER) and BER in the post-intervention group.

Results

The thrombolysis rate increased from ~29% in the pre-intervention group to 48% in the post-intervention group. Compared with the pre-intervention group, the median of door-to-needle time (DNT) was greatly shortened from 95 to 26 min (P < 0.001), door-to-CT time (DCT) was noticeably decreased from 20 to 18 min (P < 0.001), and onset-to-needle time (OTT) significantly declined from 206 to 133 min (P = 0.001). Under the new mode after the intervention, we further analyzed the IVT delay difference between the NBER (518 patients) and BER groups (80 patients) from the post-intervention group. The median values of DNT (18 vs. 27 min, P < 0.001), DCT (10 vs. 19 min, P < 0.001), and OTT (99 vs. 143 min, P < 0.001) showed significant reductions in the BER group. The quality improvement program under the emergency platform successfully controlled the median of DNT to within 26 min.

Conclusions

Collectively, the BER mode is a feasible scheme that greatly decreased DNT in AIS patients, and the secret to success was to accomplish as much as possible before the patient arrives at the emergency room.
Mechanistic target of rapamycin signaling in human nervous system development and disease
Authors: Girodengo Marie , Ultanir Sila K. , Bateman Joseph M.
Published: September 2022

Mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that regulates fundamental cellular processes including growth control, autophagy and metabolism. mTOR has key functions in nervous system development and mis-regulation of mTOR signaling causes aberrant neurodevelopment and neurological diseases, collectively called mTORopathies. In this mini review we discuss recent studies that have deepened our understanding of the key roles of the mTOR pathway in human nervous system development and disease. Recent advances in single-cell transcriptomics have been exploited to reveal specific roles for mTOR signaling in human cortical development that may have contributed to the evolutionary divergence from our primate ancestors. Cerebral organoid technology has been utilized to show that mTOR signaling is active in and regulates outer radial glial cells (RGCs), a population of neural stem cells that distinguish the human developing cortex. mTOR signaling has a well-established role in hamartoma syndromes such as tuberous sclerosis complex (TSC) and other mTORopathies. New ultra-sensitive techniques for identification of somatic mTOR pathway mutations have shed light on the neurodevelopmental origin and phenotypic heterogeneity seen in mTORopathy patients. These emerging studies suggest that mTOR signaling may facilitate developmental processes specific to human cortical development but also, when mis-regulated, cause cortical malformations and neurological disease.
Chronic high-fat diet induces overeating and impairs synaptic transmission in feeding-related brain regions
Authors: Wang Xu , Li Haohong
Published: September 2022

Obesity is linked to overeating, which can exacerbate unhealthy weight gain. However, the mechanisms for mediating such linkages are elusive. In the current study, we hypothesized that synaptic remodeling occurs in feeding-related brain regions of obese mice. To investigate this, we established a high-fat diet (HFD)-induced obese mouse model and observed that these mice consumed excessive calories. The effect of chronic HFD feeding on lipid droplet accumulation in different brain structures was also investigated. We found that lipid droplets accumulated on the ependyma of the third ventricle (3V), which is surrounded by key areas of the hypothalamus that are involved in feeding. Then, the spontaneous synaptic activity of miniature excitatory postsynaptic current (mEPSC) and miniature inhibitory postsynaptic current (mIPSC) was recorded in these hypothalamic areas. HFD induced a decreased amplitude of mEPSC in the arcuate nucleus (ARC) and the ventromedial hypothalamus (VMH), meanwhile, increased the frequency in the VMH. In addition, HFD reduced the frequency of mIPSC in the lateral hypothalamus (LH) and increased the amplitude of mIPSC in the paraventricular nucleus of the hypothalamus (PVH). Subsequently, we also measured the synaptic activity of nucleus accumbens (NAc) neurons, which play a vital role in the hedonic aspect of eating, and discovered that HFD diminished the frequency of both mEPSC and mIPSC in the NAc. These findings suggest that chronic HFD feeding leads to lipid accumulation and synaptic dysfunction in specific brain regions, which are associated with energy homeostasis and reward regulation, and these impairments may lead to the overeating of obesity.
Woodfordia fruticosa extract nanoemulsion: Influence of processing treatment on droplet size and its assessment for in vitro antimicrobial and anti-inflammatory activity
Authors: Najda Agnieszka , Bains Aarti , Klepacka Joanna , Chawla Prince
Published: September 2022

Recently, plant-derived bioactive compounds have been utilized in the preparation of several functional food products; however, stability and water solubility are major constraints to these compounds. Therefore, to overcome this problem, the synthesis of nanoemulsion (oil in water) with varying concentrations of Woodfordia fruticosa flower extract (1%−10% w/v) was carried out and characterization of nanoemulsion was done. The average droplet size of nanoemulsion samples ranges from 149.25 to 244.33 nm. The control and WFNE3 nanoemulsion showed significantly (p < 0.05) higher thermal stability when correlated with average droplet size. An insignificant difference (p > 0.05) was observed in the average droplet size and zeta potential WFNE3 (−30.3mV) with the increased temperature rate. At varied pH ranges, WFNE3 showed significantly higher (p < 0.05) stability in comparison with the control nanoemulsion sample. In terms of ionic strength, WFNE3 nanoemulsion sample showed significantly (p < 0.05) higher stability, and with an increasing concentration of salt, the colloidal system of the WFNE3 sample showed significantly (p < 0.05) higher droplet size (318.91 nm). Therefore, the antimicrobial potential of WFNE3 nanoemulsion in comparison with extract of W. fruticosa flower extract was studied against Gram-positive Staphylococcus aureus, Gram-negative bacteria Pseudomonas aeruginosa, and fungal strain Candida albicans, respectively. WFNE3 nanoemulsion sample in comparison to flower extract showed a significantly higher (p < 0.05) zone of inhibition against gram-negative bacteria as compared to the control nanoemulsion sample upon storage for 7 days. WFNE3 nanoemulsion sample showed significant (p < 0.05) higher inhibition of protein denaturation (57.89%−87.65%) and (55.36%−83.58%) in comparison to control nanoemulsion sample (54.67%−80.28%) and flower extract (51.56%−79.36%), respectively. Due to these biological activities, the WFNE3 nanoemulsion sample could be scaled up to the industrial level for the formulation of varied types of functional foods.