Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Evaluation of STEAP1 Targeting Chimeric Antigen Receptors with Different Costimulatory Domains and Spacers

We have developed a chimeric antigen receptor (CAR) against the six-transmembrane epithelial antigen of prostate-1 (STEAP1), which is expressed in prostate cancer, Ewing sarcoma, and other malignancies. In the present study, we investigated the effect of substituting costimulatory domains and spacers in this STEAP1 CAR. We cloned four CAR constructs with either CD28 or 4-1BB costimulatory domains, combined with a CD8a-spacer (sp) or a mutated IgG-spacer. The CAR T-cells were evaluated in short- and long-term in vitro T-cell assays, measuring cytokine production, tumor cell killing, and CAR T-cell expansion and phenotype. A xenograft mouse model of prostate cancer was used for in vivo comparison. All four CAR constructs conferred CD4+ and CD8+ T cells with STEAP1-specific functionality. A CD8sp_41BBz construct and an IgGsp_CD28z construct were selected for a more extensive comparison. The IgGsp_CD28z CAR gave stronger cytokine responses and killing in overnight caspase assays. However, the 41BB-containing CAR mediated more killing (IncuCyte) over one week. Upon six repeated stimulations, the CD8sp_41BBz CAR T cells showed superior expansion and lower expression of exhaustion markers (PD1, LAG3, TIGIT, TIM3, and CD25). In vivo, both the CAR T variants had comparable anti-tumor activity, but persisting CAR T-cells in tumors were only detected for the 41BBz variant. In conclusion, the CD8sp_41BBz STEAP1 CAR T cells had superior expansion and survival in vitro and in vivo, compared to the IgGsp_CD28z counterpart, and a less exhausted phenotype upon repeated antigen exposure. Such persistence may be important for clinical efficacy.
The Impact of Financial Inclusion on Economic Growth: ARDL Approach

This study investigates the impact of financial inclusion on economic growth in Jordan from 2000 to 2021. Employing an Autoregressive Distributed Lag (ARDL) approach, we examined the temporal relationship between financial inclusion indicators and economic growth. Our analysis reveals a bidirectional causality, indicating that financial inclusion not only propels economic growth but is also bolstered by it. The findings challenge the initial hypothesis of a unidirectional relationship, suggesting a more intricate interaction between financial inclusion and economic prosperity in emerging economies. The Granger causality test results significantly support the notion of mutual reinforcement between these variables. This study contributes to the empirical literature by highlighting the symbiotic relationship within the Jordanian context and suggests that enhancing financial inclusion can be a strategic tool for sustainable economic development. The research also underscores the need for considering environmental implications and the burgeoning digital financial services sector in future policy-making. Suggested future research includes comparative regional studies, incorporation of qualitative methods, and exploration of the environmental impacts of financial inclusion. The study’s conclusions are instrumental for policymakers and stakeholders in crafting informed strategies to leverage financial inclusion for economic growth.
Mucosal Melanoma Clinical Management and Prognostic Implications: A Retrospective Cohort Study

Simple Summary Mucosal melanoma (MM) is a rare melanoma subtype that affects mucosal surfaces of the head and neck, anorectal region, and vulvovaginal area. Due to its rarity, the management, monitoring, and treatment of MM lack standardization, often relying on protocols designed for cutaneous melanoma (CM). In this retrospective, registry-based cohort study, we analyzed epidemiological and histological data together with the treatments administered to gain insights into the disease’s behavior, treatment patterns, and potential predictors of survival. Our findings reveal that lower disease stage, thinner Breslow depth, and surgical resection are associated with improved overall survival, while age, sex, radiotherapy, and BRAF mutant status do not significantly affect survival. Standard systemic management typically includes immunotherapy (anti-PD-1 or anti-PD-1 and anti-CTLA-4). For cases with BRAF or c-KIT mutations, targeted therapies may be considered. The prognosis is unfavorable, with a survival rate of less than 50% at 2 years. Abstract Mucosal melanoma (MM) is an uncommon melanoma subtype affecting mucosal surfaces of the head and neck, anorectal region, and vulvovaginal area. We aimed to present our experience at a tertiary-level hospital regarding MM diagnosis, management, monitoring of progression, mutations, and outcome predictors. We performed a registry-based cohort study including MM cases diagnosed from 2012 to 2022 and retrospectively characterized somatic mutations on BRAF, NRAS and c-KIT. We employed Kaplan–Meier curves, log-rank tests, and Cox regression analysis to explore prognostic factors and survival outcomes in a cohort of 35 patients, mainly women (63%) with a median age of 70 years. Predominantly, MM occurred in the vulvovaginal region (48.6%). At diagnosis, 28.6% had lymph node involvement, and 31.4% also had distant metastasis. Mutations in BRAF and c-KIT were identified in 3/35 (9%) and 2/6 patients (33%), respectively. Surgery was performed in 71.4% of patients, and most received systemic treatment (65.7%). Lower disease stage, thinner Breslow depth, and surgical resection were associated with improved overall survival. Notably, age, sex, radiotherapy, and BRAF mutant status did not affect survival. Standard management typically involves immunotherapy. Cases with BRAF or c-KIT mutations may be considered for targeted therapies. Unfortunately, MM prognosis remains unfavorable, with a less than 50% survival rate at 2 years.
Optimization of Breakpoint Chlorination Technologies for Drinking Water Treatment: a Hungarian Case Study

Ammonium ion is one of the major pollutants found in drinking water sources in Hungary, especially in deep aquifers. under oxidative conditions, ammonium can transform into nitrite ions in the water system, posing potential health risks. In Hungary mostly biological process or breakpoint chlorination are used to eliminate ammonium ion from raw water during the drinking water treatment process. When breakpoint chlorination is applied, harmful by-products are formed. Trihalomethanes concentrations have long been regulated in Hungary, therefore during the design and optimization of the breakpoint technologies trihalomethane concentrations have been considered. However, haloacetic acids (HAA5) and chlorate ion have been recently regulated in accordance with EU Directive 2020/2184. Chlorate is a by-product that appears in treated water when sodium hypochlorite is used in breakpoint chlorination.Experiments were carried out at four Hungarian case study areas to determine the optimal strategy for breakpoint chlorination: applying higher chlorine dosages with lower contact times, or lower chlorine dosages with higher contact times. The investigations concluded that the preferable dosing strategy is to use lower chlorine concentrations and longer contact times. This approach reduces chemical demand (cost-effective) and has a neutral effect on THMs formation. it can be concluded that when the raw water contains ammonium ion concentrations above 0.5 mg/l, the use of sodium hypochlorite may raise concerns due to elevated chlorate ion levels in the treated water, particularly during summer. Further research is required to expand the optimization strategy, considering not only ammonium and trihalomethane concentrations but also chlorate concentrations.
Exploring Sustainable Economic Growth: Promoting Green Development Productivity through Decentralized Environmental Policy and Regional Competitiveness

The freedom of regions in regulating territories is now being promoted with the decentralization of environmental policies. This policy serves as the forerunner in empowering regions to function autonomously, thereby playing a role in practical politics. Therefore, this research aimed to analyze the role of decentralization of environmental policy and local government competition in navigating green development productivity in Indonesia. The slack base model and dynamic panel regression were used to generalize the method of the moment. The results showed that the decentralization of environmental policies and local government competition negatively affected the productivity of green development. Meanwhile, budget allocations for research and development, along with strategic initiatives in economic sectors such as agriculture and mining, showed a substantial positive effect.
Continuous Hydrological Modeling using Soil Moisture Accounting Algorithm in Vamsadhara River Basin, India

In this study, a continuous soil moisture accounting (SMA) algorithm was used in a Hydrologic Engineering Center- Hydrologic Modeling System (HEC-HMS) to model stream flow in the Vamsadhara River Basin in India. The spatial domain of the catchment was discretised into smaller sub-basins to account for catchment heterogeneity in terms of topography, land use and soil. The SMA algorithm in HEC-HMS was calibrated using data from 1984 to 1989, and has been validated for the period from 1990 to 1993 on a continuous time scale. Statistical and visual evaluation was conducted to determine the performance of the HEC-HMS model in the Vamsadhara River Basin. For the calibration period, the performance of the model ranges from good to very good with a coefficient of determination R 2 =0.71, Nash-Sutcliffe Efficiency EFF=0.701, percentage error in volume PEV=2.64%, percentage error in peak PEP=0.21%, and index of agreement d=0.94. Similarly, the model performance for the validation period ranges from good to very good with R 2 =0.78, EFF=0.762, PEV=12.33%, PEP = -15.2%, and d= 0.93. Sensitivity analysis of model parameters has also been conducted and the ranking of different parameters have been assigned based on their sensitivity in terms of percent change in simulated runoff volume. Sensitivity analysis helps to understand the behaviour of the model. Overall, the SMA procedure in the HEC-HMS conceptual model performed satisfactorily and can be used for long-term runoff modeling in the Vamsadhara River Basin.
Improving Clostridioides difficile Infectious Disease Treatment Response via Adherence to Clinical Practice Guidelines

Clostridioides difficile (C. difficile) is a predominant nosocomial infection, and guidelines for improving diagnosis and treatment were published in 2017. We conducted a single-center, retrospective 10-year cohort study of patients with primary C. difficile infectious disease (CDID) at the largest referral Lithuanian university hospital, aiming to evaluate the clinical and laboratory characteristics of CDID and their association with the outcomes, as well as implication of concordance with current Clinical Practice Guidelines. The study enrolled a total of 370 patients. Cases with non-concordant CDID treatment resulted in more CDID-related Intensive Care Unit (ICU) admissions (7.5 vs. 1.8%) and higher CDID-related mortality (13.0 vs. 1.8%) as well as 30-day all-cause mortality (61.0 vs. 36.1%) and a lower 30-day survival compared with CDID cases with concordant treatment (p < 0.05). Among cases defined by two criteria for severe CDID, only patients with non-concordant metronidazole treatment had refractory CDID (68.8 vs. 0.0%) compared with concordant vancomycin treatment. In the presence of non-concordant metronidazole treatment for severe CDID, only cases defined by two severity criteria had more CDID-related ICU admissions (18.8 vs. 0.0%) and higher CDID-related mortality (25.0 vs. 2.0%, p < 0.05) compared with cases defined by one criterion. Severe comorbidities and the continuation of concomitant antibiotics administered at CDID onset reduced (p < 0.05) the 30-day survival and increased (p = 0.053) 30-day all-cause mortality, with 57.6 vs. 10.7% and 52.0 vs. 25.0%, respectively. Conclusions: CDID treatment non-concordant with the guidelines was associated with various adverse outcomes. In CDID with leukocytes ≥ 15 × 109/L and serum creatinine level > 133 µmol/L (>1.5 mg/dL), enteral vancomycin should be used to avoid refractory response, as metronidazole use was associated with CDID-related ICU admission and CDID-related mortality. Severe comorbidities worsened the outcomes as they were associated with reduced 30-day survival. The continuation of concomitant antibiotic therapy increased 30-day all-cause mortality; thus, it needs to be reasonably justified, deescalated or stopped.
Fire‐Induced Carbon Loss and Tree Mortality in Siberian Larch Forests

Climate change is intensifying the fire regime across Siberia, with the potential to alter carbon combustion and post‐fire carbon re‐accumulation trajectories. Few field‐based estimates of fire severity (e.g., carbon combustion and tree mortality) exist in Siberian larch forests (Larix spp.), which limits our ability to project how an intensified fire regime will affect regional and global climate feedbacks. Here, we present field‐based estimates of fire‐induced tree mortality and carbon loss in eastern Siberian larch forests. Our results suggest that fires in this region result in high tree mortality (means of 83% and 76% at Arctic and subarctic sites, respectively). In both absolute and relative terms, aboveground carbon loss following fire is higher in Siberian larch forests than in North America, but belowground carbon loss is considerably lower. This suggests fundamental differences in wildfire behavior and carbon dynamics between dominant vegetation types across the boreal biome.
Initial deflection of middle‐latitude Pi2 pulsations in the premidnight sector: Remote detection of oscillatory upward field‐aligned current at substorm onset

In this study, we examined middle‐ and low‐latitude Pi2 events to address the following two issues regarding the well‐known substorm current wedge (SCW) model for Pi2 pulsations: (1) the center of the SCW, which is estimated using the Pi2 polarization pattern, is not always collocated with that determined using the magnetic bay pattern; and (2) although ideally Pi2 hodograms would be linear, they tend to become circular. In this study, auroral breakup events were identified from Polar Ultraviolet Imager data. We assumed that the ionospheric footprint of the upward field‐aligned current (FAC) in each event was located at the position of the auroral breakup and subsequently calculated the signature of the magnetic variation at the middle‐latitude station Zyryanka (ZYK; GMLAT = 59.6°) that was generated by the upward FAC. In order to examine the magnetic effects of the upward FAC, we selected Pi2 events that were observed when ZYK was located on the duskward side of the auroral breakup location. A total of 112 events were selected and analyzed in this study. It was found that the location of the upward FAC of the SCW could be estimated more accurately by using an azimuth value predicted based on the initial deflection of the middle‐latitude Pi2. Our results suggest that the circular shapes of Pi2 polarization curves are caused by the delayed driven Alfvénic waves that are superimposed on the geomagnetic northward components of SCW oscillations.
A Longitudinal Examination of Student Approaches to Learning and Metacognition

Student Approaches to Learning (SAL) mainly consists of two contradictory approaches (surface and deep learning) to learning that have been extensively studied in educational research. Metacognition, which refers to the process of thinking about one’s thinking, has been shown to play a crucial role in helping students shift from a surface to a deep approach to learning. The current study collected data using two questionnaires (RSPQ-2F& MAI) from 1329 students. Both metacognition and learning approaches showed medium correlations and an effect of the year of study. A crossed-lagged model shows no effect of deep learning on metacognitive knowledge or regulation, although this does increase significantly over time. Overall, the study’s findings suggest a complex yet clear relationship between student learning approaches and their final grade outcomes. Students will lean towards more surface learning as their (perceived) workload increases and assessments become more challenging. These findings suggest that teachers and policy makers should seek ways to increase deep learning methods, possibly using metacognitive skills training.
Social media impact on trading behavior: An examination among Indonesian young adult investors with capital market literacy as a mediator

The decline in financial literacy about capital markets among Indonesians raises concerns that the growing number of investors is at risk of financial fraud. This study introduces a novel approach to comprehensively examine how Indonesian young adults make investment choices, mainly when influenced by social media and their different literacy levels about financial markets in the digital age context. The central and dual roles of capital market literacy as an independent and intervening variable expand upon the existing framework of related studies. An empirical online survey with a valid sample of 314 respondents from Indonesia is used as the primary data for the study. Using the partial structural equation model, our results indicate that both social media and capital market literacy directly and positively impact investors' trading behavior. This suggests that a deeper understanding of capital market literacy, coupled with the influence of social media, plays a crucial role in shaping how investors engage in trading activities. Furthermore, this study also found that the mediating role of capital market literacy significantly affects trading behavior, indicating its importance in explaining how social media influences investment decisions among young adults.
Treatment with Leiurus quinquestratus scorpion venom ameliorates the histopathological changes of type-2 diabetic rats' splenic tissues.

Type 2 diabetes mellitus (T2-DM) is a chronic metabolic disorder characterized by tissue resistance to insulin action. Leiurus quinquestriatus venom (LQV) contains a variety of bioactive components that can be used for the treatment of various diseases. This study aimed to determine the ameliorative role of LQV on the histopathological changes in splenic tissues of T2-DM rats. Forty male Sprague Dawley rats were divided into 4 groups ( n = 10) as follows; Gp1 (Control group) was fed on a normal balanced diet. Gp2 (Diabetic group) was fed on a high-fat diet (HFD) for 12 weeks and then injected with streptozotocin (STZ) (30 mg/kg) i.p. Diabetic Gp3 and Gp4 groups had been injected with metformin (Met) (150 mg/kg) or LQV (1/10 of LD 50 ), respectively. After two months of treatment, the total body weight relative splenic weight changes, and blood glucose. Also, histopathological and immunohistochemical investigations (CD-3 immunoreactive antibody) in splenic tissues were examined. The results showed that induction of T2-DM in rats led to a significant decrease in the total body weight (-38.56%), relative spleen weight (0.23 ± 0.03), and increase in the level of blood glucose (382.56 ± 2.77 mg/dL). In addition, several histopathological and immunohistochemical changes were observed in splenic diabetic tissues. The treatment of T2-DM rats with LQV led to an improvement in the total body weight of rats (4.07%), relative spleen weight (0.40 ± 0.02), decrease in the blood glucose levels (115.47 ± 1.07 mg/dL), ameliorated the histopathological and immunohistochemical changes occurred in splenic tissues of T2-DM rats.
Managing Finances for Family Education amidst the COVID-19 Pandemic and its Consequences

This study investigates the management of family education expenses in the context of the COVID-19 epidemic and assesses the subsequent social and economic implications. The study was conducted in the Central Sulawesi village of Pasigala using a qualitative research approach and a factual exposure standpoint. The data collection process used methods like observation, interviews, and documentation. Subsequently, the gathered data underwent analysis using the Miles and Huberman model, encompassing data reduction, presentation, and verification. The research outcomes underscore the significance of effective financial management in meeting familial, educational, and financial obligations during the COVID-19 pandemic. Additionally, the pandemic has notably affected social dynamics and economic conditions. Socially, there has been a shift in values and behaviors among the population, while economically, there has been a decline in individuals' income. These findings lead to the conclusion that the COVID-19 pandemic has indeed influenced the financial management of family education. Consequently, the study recommends implementing robust financial management practices in family education to ensure resilience in facing unforeseen challenges.
Beyond Language and Culture: A Qualitative Exploration of Mental Health Barriers for Chinese International Students Seeking Therapy in the U.S.

This qualitative study explores the experiences and attitudes of Chinese international students in the U.S. towards psychotherapy, with an emphasis on identifying potential barriers and facilitators to their mental health treatment. Data were drawn from individual experiences of undergraduate and graduate Chinese international students who had engaged in therapy in the U.S. A grounded theory approach was employed to dissect these experiences and assess their attitudes towards psychotherapy. The grounded theory identified several themes from the students’ therapeutic experiences, such as: the inconsequential role of language barriers, the significant yet not prohibitive impact of cultural differences, the critical role of health insurance, the influence of therapists’ professional demeanor, and the correlation between mental health knowledge and attitudes towards therapy. Interestingly, the study also unveiled an emergent theme concerning professional boundaries within therapy. These findings suggest that while language and cultural differences might not be direct obstacles to therapy, factors such as therapists’ backgrounds and attitudes, insurance coverage, and accessibility can pose substantial challenges to Chinese international students seeking mental health treatment. Importantly, a heightened level of mental health knowledge was associated with more positive attitudes toward therapy. As a culmination of these findings, we formu- lated a triadic model emphasizing cultural understanding within the therapeutic setting, service accessibility, and mental health knowledge as key influences on the psychotherapy experiences of Chinese international students.