bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic regulation as a therapeutic target in the malaria parasite Plasmodium falciparum
Authors: Reyser Thibaud , Paloque Lucie , Augereau Jean-Michel , Di Stefano Luisa , Benoit-Vical Françoise
Published: February 2024

Over the past thirty years, epigenetic regulation of gene expression has gained increasing interest as it was shown to be implicated in illnesses ranging from cancers to parasitic diseases. In the malaria parasite, epigenetics was shown to be involved in several key steps of the complex life cycle of Plasmodium, among which asexual development and sexual commitment, but also in major biological processes like immune evasion, response to environmental changes or DNA repair. Because epigenetics plays such paramount roles in the Plasmodium parasite, enzymes involved in these regulating pathways represent a reservoir of potential therapeutic targets. This review focuses on epigenetic regulatory processes and their effectors in the malaria parasite, as well as the inhibitors of epigenetic pathways and their potential as new anti-malarial drugs. Such types of drugs could be formidable tools that may contribute to malaria eradication in a context of widespread resistance to conventional anti-malarials.
IDH2/R140Q mutation confers cytokine-independent proliferation of TF-1 cells by activating constitutive STAT3/5 phosphorylation
Authors: Yang Jie , Chen Jiao , Chang Jingjie , Sun Xiaoyan , Wei Qingyun , Cai Xueting , Cao Peng
Published: February 2024

Background

R140Q mutation in isocitrate dehydrogenase 2 (IDH2) promotes leukemogenesis. Targeting IDH2/R140Q yields encouraging therapeutic effects in the clinical setting. However, therapeutic resistance occurs in 12% of IDH2/R140Q inhibitor treated patients. The IDH2/R140Q mutant converted TF-1 cells to proliferate in a cytokine-independent manner. This study investigated the signaling pathways involved in TF-1(R140Q) cell proliferation conversion as alternative therapeutic strategies to improve outcomes in patients with acute myeloid leukemia (AML) harboring IDH2/R140Q.

Methods

The effects of IDH2/R140Q mutation on TF-1 cell survival induced by GM-CSF withdrawal were evaluated using flow cytometry assay. The expression levels of apoptosis-related proteins, total or phosphorylated STAT3/5, ERK, and AKT in wild-type TF-1(WT) or TF-1(R140Q) cells under different conditions were evaluated using western blot analysis. Cell viability was tested using MTT assay. The mRNA expression levels of GM-CSF, IL-3, IL-6, G-CSF, leukemia inhibitory factor (LIF), oncostatin M (OSM), and IL-11 in TF-1(WT) and TF-1(R140Q) cells were quantified via RT-PCR. The secretion levels of GM-CSF, OSM, and LIF were determined using ELISA.

Results

Our results showed that STAT3 and STAT5 exhibited aberrant constitutive phosphorylation in TF-1(R140Q) cells compared with TF-1(WT) cells. Inhibition of STAT3/5 phosphorylation suppressed the cytokine-independent proliferation of TF-1(R140Q) cells. Moreover, the autocrine GM-CSF, LIF and OSM levels increased, which is consistent with constitutive STAT5/3 activation in TF-1(R140Q) cells, as compared with TF-1(WT) cells.

Conclusions

The autocrine cytokines, including GM-CSF, LIF, and OSM, contribute to constitutive STAT3/5 activation in TF-1(R140Q) cells, thereby modulating IDH2/R140Q-mediated malignant proliferation in TF-1 cells. Targeting STAT3/5 phosphorylation may be a novel strategy for the treatment of AML in patients harboring the IDH2/R140Q mutation.
Crosstalk between protein post-translational modifications and phase separation
Authors: Liu Yang , Feng Wenjuan , Wang Yunshan , Wu Bin
Published: February 2024

The phenomenon of phase separation is quite common in cells, and it is involved in multiple processes of life activities. However, the current research on the correlation between protein modifications and phase separation and the interference with the tendency of phase separation has some limitations. Here we focus on several post-translational modifications of proteins, including protein phosphorylation modification at multiple sites, methylation modification, acetylation modification, ubiquitination modification, SUMOylation modification, etc., which regulate the formation of phase separation and the stability of phase separation structure through multivalent interactions. This regulatory role is closely related to the development of neurodegenerative diseases, tumors, viral infections, and other diseases, and also plays essential functions in environmental stress, DNA damage repair, transcriptional regulation, signal transduction, and cell homeostasis of living organisms, which provides an idea to explore the interaction between novel protein post-translational modifications and phase separation.
Synergism of non-thermal plasma and low concentration RSL3 triggers ferroptosis via promoting xCT lysosomal degradation through ROS/AMPK/mTOR axis in lung cancer cells
Authors: Peng Shengjie , Chen Guodong , Yu K. N. , Feng Yue , Zhao Lele , Yang Miaomiao , Cao Wei , Almahi Waleed Abdelbagi Ahmed , Sun Mingyu , Xu Yuan , Zhao Ye , Cheng Cheng , Zhu Fengqin , Han Wei
Published: February 2024

Background

Though (1S, 3R)-RSL3 has been used widely in basic research as a small molecular inducer of ferroptosis, the toxicity on normal cells and poor pharmacokinetic properties of RSL3 limited its clinical application. Here, we investigated the synergism of non-thermal plasma (NTP) and low-concentration RSL3 and attempted to rise the sensitivity of NSCLC cells on RSL3.

Methods

CCK-8 assay was employed to detect the change of cell viability. Microscopy and flowcytometry were applied to identify lipid peroxidation, cell death and reactive oxygen species (ROS) level respectively. The molecular mechanism was inspected with western blot and RT-qPCR. A xenograft mice model was adopted to investigate the effect of NTP and RSL3.

Results

We found the synergism of NTP and low-concentration RSL3 triggered severe mitochondria damage, more cell death and rapid ferroptosis occurrence in vitro and in vivo. NTP and RSL3 synergistically induced xCT lysosomal degradation through ROS/AMPK/mTOR signaling. Furthermore, we revealed mitochondrial ROS was the main executor for ferroptosis induced by the combined treatment.

Conclusion

Our research shows NTP treatment promoted the toxic effect of RSL3 by inducing more ferroptosis rapidly and provided possibility of RSL3 clinical application.

Graphical Abstract
A Cotyledon-based Virus-Induced Gene Silencing (Cotyledon-VIGS) approach to study specialized metabolism in medicinal plants
Authors: Liu Yongliang , Lyu Ruiqing , Singleton Joshua J. , Patra Barunava , Pattanaik Sitakanta , Yuan Ling
Published: February 2024

Background

Virus-induced gene silencing (VIGS) is widely used in plant functional genomics. However, the efficiency of VIGS in young plantlets varies across plant species. Additionally, VIGS is not optimized for many plant species, especially medicinal plants that produce valuable specialized metabolites.

Results

We evaluated the efficacy of five-day-old, etiolated seedlings of Catharanthus roseus (periwinkle) for VIGS. The seedlings were vacuum-infiltrated with Agrobacterium tumefaciens GV3101 cells carrying the tobacco rattle virus (TRV) vectors. The protoporphyrin IX magnesium chelatase subunit H (ChlH) gene, a key gene in chlorophyll biosynthesis, was used as the target for VIGS, and we observed yellow cotyledons 6 days after infiltration. As expected, the expression of CrChlH and the chlorophyll contents of the cotyledons were significantly decreased after VIGS. To validate the cotyledon based-VIGS method, we silenced the genes encoding several transcriptional regulators of the terpenoid indole alkaloid (TIA) biosynthesis in C. roseus, including two activators (CrGATA1 and CrMYC2) and two repressors (CrGBF1 and CrGBF2). Silencing CrGATA1 led to downregulation of the vindoline pathway genes (T3O, T3R, and DAT) and decreased vindoline contents in cotyledons. Silencing CrMYC2, followed by elicitation with methyl jasmonate (MeJA), resulted in the downregulation of ORCA2 and ORCA3. We also co-infiltrated C. roseus seedlings with TRV vectors that silence both CrGBF1 and CrGBF2 and overexpress CrMYC2, aiming to simultaneous silencing two repressors while overexpressing an activator. The simultaneous manipulation of repressors and activator resulted in significant upregulation of the TIA pathway genes. To demonstrate the broad application of the cotyledon-based VIGS method, we optimized the method for two other valuable medicinal plants, Glycyrrhiza inflata (licorice) and Artemisia annua (sweet wormwood). When TRV vectors carrying the fragments of the ChlH genes were infiltrated into the seedlings of these plants, we observed yellow cotyledons with decreased chlorophyll contents.

Conclusions

The widely applicable cotyledon-based VIGS method is faster, more efficient, and easily accessible to additional treatments than the traditional VIGS method. It can be combined with transient gene overexpression to achieve simultaneous up- and down-regulation of desired genes in non-model plants. This method provides a powerful tool for functional genomics of medicinal plants, facilitating the discovery and production of valuable therapeutic compounds.
MicroRNA-877-5p promotes osteoblast differentiation by targeting EIF4G2 expression
Authors: Shen YingChao , Zhang Yang , Wang Qiang , Jiang Bo , Jiang XiaoWei , Luo Bin
Published: February 2024

Stimulating bone formation potentially suggests therapeutics for orthopedic diseases including osteoporosis and osteoarthritis. Osteoblasts are key to bone remodeling because they act as the only bone-forming cells. miR-877-5p has a chondrocyte-improving function in osteoarthritis, but its effect on osteoblast differentiation is unknown. Here, miR-877-5p-mediated osteoblast differentiation was studied. Real-time reverse transcriptase-polymerase chain reaction was performed to measure miR-877-5p expression during the osteogenic differentiation of MC3T3-E1 cells. Osteoblast markers, including alkaline phosphatase (ALP), collagen type I a1 chain, and osteopontin, were measured and detected by alizarin red staining and ALP staining. Potential targets of miR-877-5p were predicted from three different algorithms: starBase (http://starbase.sysu.edu.cn/), PITA (http://genie.weizmann.ac.il/pubs/mir07/mir07_data.html), and miRanda (http://www.microrna.org/microrna/home.do). It was further verified by dual luciferase reporter gene assay. The experimental results found that miR-877-5p was upregulated during the osteogenic differentiation of MC3T3-E1 cells. Overexpression of miR-877-5p promoted osteogenic differentiation, which was characterized by increased cell mineralization, ALP activity, and osteogenesis-related gene expression. Knockdown of miR-877-5p produced the opposite result. Dual luciferase reporter gene assay showed that miR-877-5p directly targeted eukaryotic translation initiation factor 4γ2 (EIF4G2). Overexpression of EIF4G2 inhibited osteogenic differentiation and reversed the promoting effect of overexpression of miR-135-5p on osteogenic differentiation. These results indicate that miR-877-5p might have a therapeutic application related to its promotion of bone formation through targeting EIF4G2.
Defining usual care comparators when designing pragmatic trials of complex health interventions: a methodology review
Authors: Turner Katrina M. , Huntley Alyson , Yardley Tom , Dawson Sarah , Dawson Shoba
Published: February 2024

Background

Pragmatic trials evaluating complex health interventions often compare them to usual care. This comparator should resemble care as provided in everyday practice. However, usual care can differ for the same condition, between patients and practitioners, across clinical sites and over time. Heterogeneity within a usual care arm can raise methodological and ethical issues. To address these it may be necessary to standardise what usual care entails, although doing so may compromise a trial’s external validity. Currently, there is no guidance detailing how researchers should decide the content of their usual care comparators. We conducted a methodology review to summarise current thinking about what should inform this decision.

Methods

MEDLINE, Embase, CINAHL and PsycINFO were searched from inception to January 2022. Articles and book chapters that discussed how to identify or develop usual care comparators were included. Experts in the field were also contacted. Reference lists and forward citation searches of included articles were screened. Data were analysed using a narrative synthesis approach.

Results

One thousand nine hundred thirty records were identified, 1611 titles and abstracts screened, 112 full texts screened, and 16 articles included in the review. Results indicated that the content of a usual care comparator should be informed by the aims of the trial, existing care practices, clinical guidelines, and characteristics of the target population. Its content should also be driven by the trial’s requirements to protect participants, inform practice, and be methodologically robust, efficient, feasible and acceptable to stakeholders. When deciding the content of usual care, researchers will need to gather information about these drivers, balance tensions that might occur when responding to different trial objectives, and decide how usual care will be described and monitored in the trial.

Discussion

When deciding the content of a usual care arm, researchers need to understand the context in which a trial will be implemented and what the trial needs to achieve to address its aim and remain ethical. This is a complex decision-making process and trade-offs might need to be made. It also requires research and engagement with stakeholders, and therefore time and funding during the trial’s design phase.

Methodology review registration

PROSPERO CRD42022307324.
Novel quinazolines bearing 1,3,4-thiadiazole-aryl urea derivative as anticancer agents: design, synthesis, molecular docking, DFT and bioactivity evaluations
Authors: Masoudinia Sara , Samadizadeh Marjaneh , Safavi Maliheh , Bijanzadeh Hamid Reza , Foroumadi Alireza
Published: February 2024

A novel series of 1-(5-((6-nitroquinazoline-4-yl)thio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives 8 were designed and synthesized to evaluate their cytotoxic potencies. The structures of these obtained compounds were thoroughly characterized by IR, 1H, and 13C NMR, MASS spectroscopy and elemental analysis methods. Additionally, their in vitro anticancer activities were investigated using the MTT assay against A549 (human lung cancer), MDA-MB231 (human triple-negative breast cancer), and MCF7 (human hormone-dependent breast cancer). Etoposide was used as a reference marketed drug for comparison. Among the compounds tested, compounds 8b and 8c demonstrated acceptable antiproliferative activity, particularly against MCF7 cells. Considering the potential VEGFR-2 inhibitor potency of these compounds, a molecular docking study was performed for the most potent compound, 8c, to determine its probable interactions. Furthermore, computational investigations, including molecular dynamics, frontier molecular orbital analysis, Fukui reactivity descriptor, electrostatic potential surface, and in silico ADME evaluation for all compounds were performed to illustrate the structure–activity relationship (SAR).
Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry—a historical cohort study
Authors: Ichinose Kunihiro , Sato Shuntaro , Igawa Takashi , Okamoto Momoko , Takatani Ayuko , Endo Yushiro , Tsuji Sosuke , Shimizu Toshimasa , Sumiyoshi Remi , Koga Tomohiro , Kawashiri Shin-ya , Iwamoto Naoki , Tamai Mami , Nakamura Hideki , Origuchi Tomoki , Yajima Nobuyuki , Sada Ken-Ei , Miyawaki Yoshia , Yoshimi Ryusuke , Shimojima Yasuhiro , Ohno Shigeru , Kajiyama Hiroshi , Sato Shuzo , Fujiwara Michio , Kawakami Atsushi
Published: February 2024

Background

Previous studies have shown conflicting evidence regarding the incidence of cancer in patients with systemic lupus erythematosus (SLE) compared with that in healthy individuals. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus have been widely used to treat SLE; however, their effects on cancer risk remain unclear. We aimed to investigate the incidence of cancer in patients with SLE and determine the potential association between CNI use and cancer risk.

Methods

The standardized incidence ratio (SIR) of cancer among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) was calculated based on the age-standardized incidence rate of cancer reported by Japan’s Ministry of Health, Labour and Welfare. We also examined the association between CNI exposure and cancer risk, while considering potential confounding factors. The analysis accounted for confounding variables such as age, sex, smoking history, maximum glucocorticoid dose, treatment history with cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking history.

Results

The study included 704 patients with SLE (625 females; 88.8%) with a median age of 44 years [interquartile range (IQR) = 34–55] years. The median past maximum glucocorticoid dose was 40 mg/day [IQR = 30–60 mg/day], and the SDI at registration was 1 [IQR = 0–2]. Among the patients, 246 (35.1%) had smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA cohort was 1.08 (95% confidence interval [CI] = 0.74–1.43). No statistically significant risks of cancer were found in relation to CNI treatment history; the odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42–3.00), the risk ratio using standardization was 1.18 (95% CI = 0.47–2.16), and the risk ratio using inverse probability weighting was 1.8 (95% CI = 0.41–4.66).

Conclusions

The incidence of cancer in patients with SLE in the LUNA cohort did not significantly differ from that in the general population. These findings suggest that CNI treatment in this cohort did not pose a risk factor for cancer development.
Detection of gene mutation in the prognosis of a patient with arrhythmogenic right ventricular cardiomyopathy: a case report
Authors: Phan Dinh Phong , Tran Tuan Viet , Le Vo Kien , Nguyen Tuan Viet
Published: February 2024

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC), or more recently known as arrhythmogenic cardiomyopathy (ACM), is an heritable disorder of the myocardium characterized by progressive fibrofatty replacement the heart muscle and risk of ventricular arrhythmias and sudden cardiac death (SCD). We report a case study to demonstrate the role of gene mutation detection in risk stratification for primary prevention of SCD in a young patient diagnosed with ARVC.

Case presentation

A 15-year-old Asian (Vietnamese) male patient with no history of documented tachyarrhythmia or syncope and a family history of potential SCD was admitted due to palpitations. Clinical findings and work-up including cardiac magnetic resonance imaging (MRI) were highly suggestive of ARVC. Gene sequencing was performed for SCD risk stratification, during which PKP2 gene mutation was found. Based on the individualized risk stratification, an ICD was implanted for primary prevention of SCD. At 6 months post ICD implantation, the device detected and successfully delivered an appropriate shock to terminate an episode of potentially fatal ventricular arrhythmia. ICD implantation was therefore proven to be appropriate in this patient.

Conclusions

While gene mutations are known to be an important factor in the diagnosis of ARVC according to the 2010 Task Force Criteria and recent clinical guidelines, their role in risk stratification of SCD remains controversial. Our case demonstrated that when used with other clinical factors and family history, this information could be helpful in identifying appropriate indication for ICD implantation.
A systematic review and meta-analysis of balance training in patients with chronic ankle instability
Authors: Guo Yiwei , Cheng Tianyue , Yang Zihao , Huang Yonglei , Li Ming , Wang Taoli
Published: February 2024

Background

Chronic ankle instability (CAI) is a common yet serious problem for elder patients. This meta-analysis aimed to evaluate the effects of balance training for CAI, to provide evidence for the clinical treatment, and care of CAI patients.

Methods

Two investigators searched PubMed, EMBASE, Science Direct, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Weipu Databases up to May 20, 2023, for randomized controlled trials (RCTs) on the effects of balance training for CAI. The mean difference (MD) with 95% confidence intervals (95%CIs) was calculated for each outcome with a fixed or random effect model. Review Manager 5.3 software was used for meta-analysis.

Results

Nine RCTs involving 341 patients were included. Meta-analysis results showed that compared with blank controls, balanced training treatment of CAI could significantly improve the score of CAI [MD = 3.95, 95% CI (3.26, 4.64), P < 0.00001], SEBT-PM [MD = 4.94, 95% CI (1.88, 8.00), P = 0.002], SEBT-PL [MD = 5.19, 95% CI (1.57, 8.81), P = 0.005], and FAAM Sports [MD = 17.74, 95% CI (14.36, 21.11), P < 0.00001]. Compared with strength training, balance training treatment of CAI improved the score of CAIT [MD = 2.36, 95% CI (0.29, 4.44), P = 0.03], FAAM-ADL [MD = 4.06, 95% CI (1.30, 6.83), P = 0.004].

Conclusion

The analysis outcomes indicate that balance training enhances daily activity capability, motor function, and dynamic balance to different extents. Additionally, when comparing the results of balance training and strength training, no significant difference was observed between the two methods in improving the dynamic stability of CAI patients. However, it is noteworthy that balance training exhibits a more pronounced impact on enhancing functional scale scores.
Decreased TLR7 expression was associated with airway eosinophilic inflammation and lung function in asthma: evidence from machine learning approaches and experimental validation
Authors: Yan Kemin , Liang Yuxia
Published: February 2024

Background

Asthma is a global public health concern. The underlying pathogenetic mechanisms of asthma were poorly understood. This study aims to explore potential biomarkers associated with asthma and analyze the pathological role of immune cell infiltration in the disease.

Methods

The gene expression profiles of induced sputum were obtained from Gene Expression Omnibus datasets (GSE76262 and GSE137268) and were combined for analysis. Toll-like receptor 7 (TLR7) was identified as the core gene by the intersection of two different machine learning algorithms, namely, least absolute shrinkage and selector operation (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE), and the top 10 core networks based on Cytohubba. CIBERSORT algorithm was used to analyze the difference of immune cell infiltration between asthma and healthy control groups. Finally, the expression level of TLR7 was validated in induced sputum samples of patients with asthma.

Results

A total of 320 differential expression genes between the asthma and healthy control groups were screened, including 184 upregulated genes and 136 downregulated genes. TLR7 was identified as the core gene after combining the results of LASSO regression, SVM-RFE algorithm, and top 10 hub genes. Significant differences were observed in the distribution of 13 out of 22 infiltrating immune cells in asthma. TLR7 was found to be closely related to the level of several infiltrating immune cells. TLR7 mRNA levels were downregulated in asthmatic patients compared with healthy controls (p = 0.0049). The area under the curve of TLR7 for the diagnosis of asthma was 0.7674 (95% CI 0.631–0.904,p = 0.006). Moreover, TLR7 mRNA levels were negatively correlated with exhaled nitric oxide fraction (r = − 0.3268,p = 0.0347) and the percentage of peripheral blood eosinophils (%) (r = − 0.3472,p = 0.041), and positively correlated with forced expiratory volume in the first second (FEV1) (% predicted) (r = 0.3960,p = 0.0071) and FEV1/forced vital capacity (r = 0.3213,p = 0.0314) in asthmatic patients.

Conclusions

Decreased TLR7 in the induced sputum of eosinophilic asthmatic patients was involved in immune cell infiltration and airway inflammation, which may serve as a new biomarker for the diagnosis of eosinophilic asthma.
Characterization of T-Cell receptor repertoire in immunoglobulin a nephropathy
Authors: Ho Szu-Ying , Kao Chih-Chin , Chang Che-Mai , Chou Yi-Chien , Luo Wei-Tzu , Chou Wan-Hsuan , Tsai I-Lin , Wu Mai-Szu , Chang Wei-Chiao
Published: February 2024

Immunoglobulin A nephropathy (IgAN) is an autoimmune disease characterized by abnormal IgA deposition in glomerulus. Current diagnosis of IgAN still depends on renal biopsy, an invasive method that might increase the risk of clinical outcomes. Therefore, we aimed to explore the characteristics of T cell repertoire in IgAN from peripheral blood samples for identifying innovative diagnostic biomarkers. Herein, we included 8 IgAN patients, 25 non-IgAN patients, and 10 healthy controls in the study. A high-throughput immune repertoire sequencing was conducted to investigate the T-cell receptor beta-chain (TCRβ) repertoire of peripheral blood. Characteristics of TCRβ repertoire were assessed for these three distinct groups. A reduced TCRβ repertoire diversity was observed in IgAN patients compared to non-IgAN and healthy individuals. A skewed distribution toward shorter TCRβ complementarity determining region (CDR3) length was found in non-IgAN relative to IgAN patients. In addition, the differences in usages of five TRBV genes (TRBV5-4, TRBV6-4, TRBV12-1, TRBV16, and TRBV21-1) were identified between IgAN, non-IgAN, and healthy subjects. Of note, the TRBV6-4 gene, which is associated with mucosal-associated invariant T (MAIT) cells, exhibited higher usage in IgAN patients, suggesting potential importance of MAIT cells in IgAN. In short, our findings supported TCR repertoire characteristics as potential biomarkers for IgAN diagnosis.
Characteristics of departments with high-use of active learning in introductory STEM courses: implications for departmental transformation
Authors: Lau Alexandra C. , Henderson Charles , Stains Marilyne , Dancy Melissa , Merino Christian , Apkarian Naneh , Raker Jeffrey R. , Johnson Estrella
Published: February 2024

Background

It is well established in the literature that active learning instruction in introductory STEM courses results in many desired student outcomes. Yet, regular use of high-quality active learning is not the norm in many STEM departments. Using results of a national survey, we identified 16 departments where multiple instructors reported using high levels of active learning in their introductory chemistry, mathematics, or physics courses. We conducted interviews with 27 instructors in these 16 departments to better understand the characteristics of such departments.

Results

Using grounded theory methodology, we developed a model that highlights relevant characteristics of departments with high use of active learning instruction in their introductory courses. According to this model, there are four main, interconnected characteristics of such departments: motivated people, knowledge about active learning, opportunities, and cultures and structures that support active learning. These departments have one or more people who are motivated to promote the use of active learning. These motivated people have knowledge about active learning as well as access to opportunities to promote the use of active learning. Finally, these departments have cultures and structures that support the use of active learning. In these departments, there is a positive feedback loop that works iteratively over time, where motivated people shape cultures/structures and these cultures/structures in turn increase the number and level of commitment of the motivated people. A second positive feedback loop was found between the positive outcome of using active learning instruction and the strengthening of cultures/structures supportive of active learning.

Conclusions

According to the model, there are two main take-away messages for those interested in promoting the use of active learning. The first is that all four components of the model are important. A weak or missing component may limit the desired outcome. The second is that desired outcomes are obtained and strengthened over time through two positive feedback loops. Thus, there is a temporal aspect to change. In all of the departments that were part of our study, the changes took at minimum several years to enact. While our model was developed using only high-use of active learning departments and future work is needed to develop the model into a full change theory, our results do suggest that change efforts may be made more effective by increasing the robustness of the four components and the connections between them.
Landslide susceptibility assessment of South Korea using stacking ensemble machine learning
Authors: Lee Seung-Min , Lee Seung-Jae
Published: February 2024

Background

Landslide susceptibility assessment (LSA) is a crucial indicator of landslide hazards, and its accuracy is improving with the development of artificial intelligence (AI) technology. However, the AI algorithms are inconsistent across regions and strongly dependent on input variables. Additionally, LSA must include historical data, which often restricts the assessment to the local scale and single landslide events.

Methods

In this study, we performed an LSA for the entirety of South Korea. A total of 30 input variables were constructed, consisting of 9 variables from past climate model data MK-PRISM, 12 topographical factors, and 9 environmental factors. Sixteen machine learning algorithms were used as basic classifiers, and a stacking ensemble was used on the four algorithms with the highest area under the curve (AUC). Additionally, a separate assessment model was established for areas with a risk of landslides affecting areas larger than 1 ha.

Results

The highest-performing classifier was CatBoost, with an AUC of ~ 0.89 for both assessments. Among the input variables, distance of road, daily maximum precipitation, digital elevation model, and soil depth were the most influential. In all landslide events, CatBoost, lightGBM, XGBoost, and Random Forest had the highest AUC in descending order; in large landslide events, the order was CatBoost, XGBoost, Extra Tree, and lightGBM. The stacking ensemble enabled the construction of two landslide susceptibility maps.

Conclusions

Our findings provide a statistical method for constructing a high-resolution (30 m) landslide susceptibility map on a country scale using diverse natural factors, including past climate data.
Classification of geogrid reinforcement in aggregate using machine learning techniques
Authors: Aregbesola Samuel Olamide , Byun Yong-Hoon
Published: February 2024

The present study proposes a novel ML methodology for differentiating between unstabilized aggregate specimens and those stabilized with triangular and rectangular aperture geogrids. This study utilizes the compiled experimental results obtained from stabilized and unstabilized specimens under repeated loading into a balanced, moderate-sized database. The efficacy of five ML models, including tree-ensemble and single-learning algorithms, in accurately identifying each specimen class was explored. Shapley’s additive explanation was used to understand the intricacies of the models and determine global feature importance ranking of the input variables. All the models could identify the unstabilized specimen with an accuracy of at least 0.9. The tree-ensemble models outperformed the single-learning models when all three classes (unstabilized specimens and specimens stabilized by triangular and rectangular aperture geogrids) were considered, with the light gradient boosting machine showing the best performance—an accuracy of 0.94 and an area under the curve score of 0.98. According to Shapley’s additive explanation, the resilient modulus and confining pressure were identified as the most important features across all models. Therefore, the proposed ML methodology may be effectively used to determine the type and presence of geogrid reinforcement in aggregates, based on a few aggregate material properties and performance under repeated loading.
The effect of transcranial direct current stimulation paired with neuromuscular electrical stimulation on swallowing function in post stroke dysphagia
Authors: El Nahas Nevine , Shokri Hossam , Refaat Ahmed , Mousa Hanaa , Hamid Aya , Abdel Monem Amr , AbuShady Eman
Published: February 2024

Background

Transcranial direct current stimulation (tDCS) and neuromuscular electrical stimulation (NMES) are noninvasive neuromodulation techniques that have shown positive effects in a variety of neurological disorders. Most protocols apply one modality at a time. Here we tested the effect of tDCS applied together with NMES on patients with dysphagia after acute stroke. To assess the efficacy of combined tDCS and NMES on improvement of dysphagia after acute stroke, guided by Fiber-optic endoscopic evaluation of swallowing (FEES). This study is a double-blinded randomized case-controlled study conducted in a University hospital. This study enrolled 48 patients diagnosed by FEES and assigned to 3 groups of 16 patients each. The first group received both tDCS and NMES, the second group received NMES only and the third group received sham NMES. Gugging Swallowing Screen (GUSS) test was done before and after intervention.

Results

Significant improvement was seen in all tested materials on GUSS test in tDCS/NMES group. While in the other two groups, there was only improvement for safety of liquid swallowing.

Conclusion

This study shows that the combined application of tDCS and NMES has an advantage in improvement of PSD over active NMES and sham NMES groups in all materials tested by GUSS.
Emerging advanced approaches for diagnosis and inhibition of liver fibrogenesis
Authors: Addissouky Tamer A. , Ali Majeed M. A. , Sayed Ibrahim El Tantawy El , Wang Yuliang
Published: February 2024

Background

Liver fibrosis results from chronic liver injury and is characterized by excessive deposition of extracellular matrix proteins including collagen. It can progress to cirrhosis and liver failure.

Main body of the abstract

Multiple cellular signaling pathways drive hepatic stellate cell activation and fibrogenesis. Advances in biomarkers, imaging modalities, and omics platforms enable noninvasive diagnosis and staging of liver fibrosis. Emerging antifibrotic approaches include medications like pirfenidone, obeticholic acid, and monoclonal antibodies targeting pro-fibrotic mediators. Cell therapies using mesenchymal stem cells demonstrate antifibrotic potential through paracrine immunosuppression. Tissue-engineered liver grafts and biomaterial carriers for localized drug delivery are promising technologies. Microfluidic liver-on-a-chip platforms with patient-derived cells provide unprecedented models to study human liver fibrosis and test drug candidates.

Short conclusion

Significant progress has elucidated mechanisms underlying liver fibrogenesis and uncovered novel therapeutic targets. Ongoing challenges include translating preclinical findings, improving antifibrotic efficacy, and enabling personalized precision medicine approaches. Further research into combinatorial therapies, biomarkers, and tissue engineering technologies will advance the treatment of liver fibrosis from all causes.
Value for money: a cost-effectiveness analysis of microplastic analytics in seawater
Authors: Meyers Nelle , Kopke Kathrin , Buhhalko Natalja , Mattsson Karin , Janssen Colin R. , Everaert Gert , De Witte Bavo
Published: February 2024

The availability of many microplastic analysis methods is challenging for researchers and policy makers when tasked with choosing optimal methods for their research question and a given budget. In this study, a cost-effectiveness analysis of methods for microplastic analysis in seawater was performed using survey data acquired from experts. Total analysis cost per method was determined accounting for labour and equipment costs, while method effectiveness was scored based on their ability to confirm the plastic nature of particles, their minimum detectable particle size, and other parameters. Results were validated and discussed during two workshops with scientists and policy makers. The resulting predictive tools allow to identify the most cost-effective methods for specific scenarios, and their associated cost. They mark an important step towards a more effective and informed approach to monitoring and managing microplastic pollution in the marine environment, ultimately contributing to the protection of marine ecosystems and human health.
Bearing capacity prediction of the concrete pile using tunned ANFIS system
Authors: Gu Wei , Liao Jifei , Cheng Siyuan
Published: February 2024

The design process for pile foundations necessitates meticulous deliberation of the calculation pertaining to the bearing capacity of the piles. The primary objective of this work was to investigate the potential use of Coot bird optimization ($${\text{CBO}}$$
CBO
) techniques in predicting the load-bearing capacity of concrete-driven piles. Despite the availability of several suggested models, the investigation of Coot bird optimization ($${\text{CBO}}$$
CBO
) for estimating the pile-carrying capacity has been somewhat neglected in this research. This work presents and validates a unique approach that combines the Coot bird optimization ($${\text{CBO}}$$
CBO
) model with the Multi-layered perceptron ($${\text{MLP}}$$
MLP
) neural network and adaptive neuro-fuzzy inference system ($${\text{ANFIS}}$$
ANFIS
). The findings of 472 different driven pile static load tests were put in a database. The proposed framework's building, validation, and testing stages were each accomplished utilizing the training set (70%), validation set (15%), and testing set (15%) of the dataset, respectively. According to the findings, $${{\text{MLP}}}_{{\text{CBO}}}$$

MLP
CBO

and $${{\text{ANFIS}}}_{{\text{CBO}}}$$

ANFIS
CBO

both offer remarkable possibilities for accurately predicting the pile-bearing capacity of a given structure. The $${R}^{2}$$

R

2

values for $${{\text{ANFIS}}}_{{\text{CBO}}}$$

ANFIS
CBO

during the training stage were 0.9874, while during the validating stage, they were 0.9785, and during the testing stage they were 0.987. After considering various kinds of performance studies and contrasting them with existing literature, it has been concluded that the $${{\text{ANFIS}}}_{{\text{CBO}}}$$

ANFIS
CBO

model provides a more appropriate calculation of the bearing capacity of concrete-driven piles.
Asymmetric acoustic splitting with the dual-layers of binary metagratings
Authors: Liu Zhengang , Chang Shuai , Xue Shibei , Ju Fangfang , Qian Shengyou
Published: February 2024

Here, we exhibit the asymmetric acoustic splitting with the dual-layers of binary metagratings (BMs), i.e., BM1 and BM2. For the positive incidence (PI) normally from the BM1 side, acoustic waves are freely transmitted through the BM1 and split into two beams with the transmitted angles at

and

, then the two beams are freely transmitted through the BM2 with the transmitted angles at

and

. For the negative incidence (NI) normally from the BM2 side, acoustic waves are wholly reflected. Hence, the asymmetric acoustic splitting is observed. Here, the dual-layers of BMs are exemplified by the coating cells with different period lengths. Excellent agreement can be observed between the numerical simulations and the theoretical analysis. Our proposal may be applied in noise control and acoustic communication.
Anomalous metallic conductivity and short-range ferromagnetic correlation in high-pressure synthesized pyrochlore
Authors: Zhao Jianfa , Deng Zheng , Zhang Jun , Peng Yi , Shi Luchuan , Min Baosen , Duan Lei , Li Wenmin , Cao Lipeng , Chen Jeng-Lung , Hu Zhiwei , Yu Runze , Jin Changqing
Published: February 2024

Iridates show fascinating properties due to the unpredictable ground states of their Ir cations. Generally, Ir5+(5d
4) systems exhibit insulating nonmagnetic states owing to the strong spin-orbit coupling (SOC). Herein a new pyrochlore iridate Hg2Ir2O7 with an Ir5+ charge state synthesized by high-pressure technique is reported. Hg2Ir2O7 crystallizes in the typical cubic pyrochlore crystal structure. The Ir5+ valence state is evidenced by the XAS spectrum. Surprisingly, Hg2Ir2O7 displays short-range ferromagnetic correlations at low temperatures as evidenced by S-shape field-dependent magnetization curves, positive magnetoresistance, and magnetic excitations in specific heat. Furthermore, it also shows metallic conduction and large electron component of specific heat. These results all indicate that Ir5+ in Hg2Ir2O7 deviates from SOC-dominated insulating nonmagnetic states.
Compliance With Federal Price Transparency Rules and Cost Estimation at United States Hospitals With Neurosurgical Training Programs
Authors: Giantini-Larsen Alexandra , Pandey Abhinav , Abou-Mrad Zaki , Tata Nalini , Barzilai Ori , Bilsky Mark , Newman W. Christopher
Published: February 2024

BACKGROUND AND OBJECTIVES:

The Centers for Medicare & Medicaid Services implemented federal requirements on January 1, 2021, under the Public Health Service Act that require hospitals to provide a list of payer-negotiated prices or “standard charges” in a machine-readable file and in a patient-friendly online estimator for standard services. We sought to assess compliance by United States hospitals associated with neurosurgical training programs with these federal requirements for 11 common neurosurgical procedures.

METHODS:

We performed a cross-sectional analysis in March 2023 of 116 United States hospitals associated with a neurosurgical training program to assess compliance with the new federal requirements to have a machine-readable, downloadable file with standard charges and a patient-friendly online estimator for two spinal procedures.

RESULTS:

A total of 110/114 (96.5%) hospitals were compliant with the requirement for a machine-readable file with payer-negotiated prices. A total of 47/110 hospitals (42.7%) were compliant with downloadable machine-readable files and reported at least one payer-negotiated price for 1 of the 11 common neurosurgical procedures. A total of 45/110 (40.9%) used bundled Diagnosis-Related Group codes, and 18/110 (16.4%) did not contain any price information for neurosurgical procedures. For neurosurgical procedures, the percent difference between the average negotiated private insurance and Medicare price per procedure ranged from 17.5% to 77.6%. Medicare and private insurance data for each procedure were available on average for 10.3 states (SD = 3.8) and 15.6 states (SD = 4.8), respectively.

CONCLUSION:

While hospital compliance with federal requirements for machine-readable files with payer-negotiated prices was high, availability of payer-negotiated prices for 4 major insurance types across 11 common neurosurgical procedures based on Current Procedural Terminology codes was sparce. Consequently, meaningful conclusions on procedure-related charges for elective procedures are difficult for patients to make because of the unintelligible format of data and a lack of reporting of charges per Current Procedural Terminology code in a comprehensive manner.
Long-range formation of the Bicoid gradient requires multiple dynamic modes that spatially vary across the embryo
Authors: Athilingam Thamarailingam , Nelanuthala Ashwin V. S. , Breen Catriona , Karedla Narain , Fritzsche Marco , Wohland Thorsten , Saunders Timothy E.
Published: February 2024

Morphogen gradients provide essential positional information to gene networks through their spatially heterogeneous distribution, yet how they form is still hotly contested, with multiple models proposed for different systems. Here, we focus on the transcription factor Bicoid (Bcd), a morphogen that forms an exponential gradient across the anterior-posterior (AP) axis of the early Drosophila embryo. Using fluorescence correlation spectroscopy we find there are spatial differences in Bcd diffusivity along the AP axis, with Bcd diffusing more rapidly in the posterior. We establish that such spatially varying differences in Bcd dynamics are sufficient to explain how Bcd can have a steep exponential gradient in the anterior half of the embryo and yet still have an observable fraction of Bcd near the posterior pole. In the nucleus, we demonstrate that Bcd dynamics are impacted by binding to DNA. Addition of the Bcd homeodomain to eGFP::NLS qualitatively replicates the Bcd concentration profile, suggesting this domain regulates Bcd dynamics. Our results reveal how a long-range gradient can form while retaining a steep profile through much of its range.
Sall4 regulates posterior trunk mesoderm development by promoting mesodermal gene expression and repressing neural genes in the mesoderm
Authors: Pappas Matthew P. , Kawakami Hiroko , Corcoran Dylan , Chen Katherine Q. , Scott Earl Parker , Wong Julia , Gearhart Micah D. , Nishinakamura Ryuichi , Nakagawa Yasushi , Kawakami Yasuhiko
Published: February 2024

The trunk axial skeleton develops from paraxial mesoderm cells. Our recent study demonstrated that conditional knockout of the stem cell factor Sall4 in mice by TCre caused tail truncation and a disorganized axial skeleton posterior to the lumbar level. Based on this phenotype, we hypothesized that, in addition to the previously reported role of Sall4 in neuromesodermal progenitors, Sall4 is involved in the development of the paraxial mesoderm tissue. Analysis of gene expression and SALL4 binding suggests that Sall4 directly or indirectly regulates genes involved in presomitic mesoderm differentiation, somite formation and somite differentiation. Furthermore, ATAC-seq in TCre; Sall4 mutant posterior trunk mesoderm shows that Sall4 knockout reduces chromatin accessibility. We found that Sall4-dependent open chromatin status drives activation and repression of WNT signaling activators and repressors, respectively, to promote WNT signaling. Moreover, footprinting analysis of ATAC-seq data suggests that Sall4-dependent chromatin accessibility facilitates CTCF binding, which contributes to the repression of neural genes within the mesoderm. This study unveils multiple mechanisms by which Sall4 regulates paraxial mesoderm development by directing activation of mesodermal genes and repression of neural genes.