Miracle-dz/UniFAR-FTUs huggingface dataset:
High Frequency of Tumor Propagating Cells in Fusion-Positive Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Fusion-positive RMS (FPRMS), expressing the PAX3/7-FOXO1, has a worse prognosis compared to the more common fusion-negative RMS (FNRMS). Although several studies reported hierarchical organization for FNRMS with the identification of cancer stem cells, the cellular organization of FPRMS is not yet clear. In this study we investigated the expression of key stem cell markers, developed a sphere assay, and investigated the seven most common FPRMS cell lines for subpopulations of tumor propagating cancer stem-like cells, also called cancer stem cells (CSCs). Moreover, loss- and gain-of-functions of the stem cell genes SOX2, OCT4, and NANOG were investigated in the same cells. Single-cell clonal analysis was performed in vitro as well as in vivo. We found that no stable CSC subpopulation could be enriched in FPRMS. Unlike depletion of PAX3-FOXO1, neither overexpression nor siRNA-mediated downregulation of SOX2, OCT4, and NANOG affected physiology of RMS cells. Every single subclone-derived cell clone initiated tumor growth in mice, despite displaying considerable heterogeneity in gene expression. FPRMS appears to contain a high frequency of tumor propagating stem-like cells, which could explain their higher propensity for metastasis and relapse. Their dependency on PAX3-FOXO1 activity reinforces the importance of the fusion protein as the key therapeutic target.
Systematic Performance Comparison of Fe3+/Fe0/Peroxymonosulfate and Fe3+/Fe0/Peroxydisulfate Systems for Organics Removal

Activated zero-valent iron (Ac-ZVI) coupled with Fe3+ was employed to activate peroxymonosulfate (PMS) and peroxydisulfate (PDS) for acid orange 7 (AO7) removal. Fe3+ was used to promote Fe2+ liberation from Ac-ZVI as an active species for reactive oxygen species (ROS) generation. The factors affecting AO7 degradation, namely, the Ac-ZVI:Fe3+ ratio, PMS/PDS dosage, and pH, were compared. In both PMS and PDS systems, the AO7 degradation rate increased gradually with increasing Fe3+ concentration at fixed Ac-ZVI loading due to the Fe3+-promoted liberation of Fe2+ from Ac-ZVI. The AO7 degradation rate increased with increasing PMS/PDS dosage due to the greater amount of ROS generated. The degradation rate in the PDS system decreased while the degradation rate in the PMS system increased with increasing pH due to the difference in the PDS and PMS activation mechanisms. On the basis of the radical scavenging study, sulfate radical was identified as the dominant ROS in both systems. The physicochemical properties of pristine and used Ac-ZVI were characterized, indicating that the used Ac-ZVI had an increased BET specific surface area due to the formation of Fe2O3 nanoparticles during PMS/PDS activation. Nevertheless, both systems displayed good reusability and stability for at least three cycles, indicating that the systems are promising for pollutant removal.
Vitamin D Receptor Gene Polymorphism and Vitamin D Status in Population of Patients with Cardiovascular Disease—A Preliminary Study

The association between vitamin D receptor (VDR) polymorphism and the risk of cardiovascular diseases (CVD) remains unclear. This study aimed to assess a relationship between the VDR genotypes, plasma concentrations of vitamin D metabolites, and the occurrence of cardiovascular and metabolic disorders. Fifty-eight patients treated for various cardiological afflictions were included. Identification of VDR polymorphisms: ApaI, TaqI, BsmI, and FokI were carried out using the PCR-RFLP method. Plasma concentrations of 25-hydroxyvitamin-D2, 25-hydroxyvitamin-D3, and 3-epi-25-hydroxyvitamin D3 were assessed by the UPLC-MS/MS method. Lower incidence of BsmI AA genotype in the studied patients was observed compared with healthy controls, but the difference was insignificant. Among patients with the TT genotype, frequency of hypertension was higher than among carriers of other ApaI genotypes (p < 0.01). In addition, carriers of the TT ApaI, TC TaqI, and GA BsmI genotypes had an increased risk of obesity, while the presence of the FokI TT genotype was associated with a higher incidence of heart failure and hypertension. In conclusion, the BsmI AA genotype can be protective against CVD, but this observation needs study on a larger group of patients. Particular VDR genotypes were associated with 25-hydroxyvitamin-D levels, and the mechanism of this association should be further investigated.
Design, Synthesis, and Cytotoxicity Assessment of [64Cu]Cu-NOTA-Terpyridine Platinum Conjugate: A Novel Chemoradiotherapeutic Agent with Flexible Linker

Maximum benefits of chemoradiation therapy with platinum-based compounds are expected if the radiation and the drug are localized simultaneously in cancer cells. To optimize this concomitant effect, we developed the novel chemoradiotherapeutic agent [64Cu]Cu-NOTA-C3-TP by conjugating, via a short flexible alkyl chain spacer (C3), a terpyridine platinum (TP) moiety to a NOTA chelator complexed with copper-64 (64Cu). The decay of 64Cu produces numerous low-energy electrons, enabling the 64Cu-conjugate to deliver radiation energy close to TP, which intercalates into G-quadruplex DNA. Accordingly, the in vitro internalization kinetic and the cytotoxic activity of [64Cu]Cu-NOTA-C3-TP and its derivatives were investigated with colorectal cancer (HCT116) and normal human fibroblast (GM05757) cells. Radiolabeling by 64Cu results in a >55,000-fold increase of cytotoxic potential relative to [NatCu]Cu-NOTA-C3-TP at 72 h post administration, indicating a large additive effect between 64Cu and the TP drug. The internalization and nucleus accumulation of [64Cu]Cu-NOTA-C3-TP in the HCT116 cells were, respectively, 3.1 and 6.0 times higher than that for GM05757 normal human fibroblasts, which is supportive of the higher efficiency of the [64Cu]Cu-NOTA-C3-TP for HCT116 cancer cells. This work presents the first proof-of-concept study showing the potential use of the [64Cu]Cu-NOTA-C3-TP conjugate as a targeted chemoradiotherapeutic agent to treat colorectal cancer.
Recent Advances in Intelligent Source Code Generation: A Survey on Natural Language Based Studies

Source Code Generation (SCG) is a prevalent research field in the automation software engineering sector that maps specific descriptions to various sorts of executable code. Along with the numerous intensive studies, diverse SCG types that integrate different scenarios and contexts continue to emerge. As the ultimate purpose of SCG, Natural Language-based Source Code Generation (NLSCG) is growing into an attractive and challenging field, as the expressibility and extremely high abstraction of the input end. The booming large-scale dataset generated by open-source code repositories and Q&A resources, the innovation of machine learning algorithms, and the development of computing capacity make the NLSCG field promising and give more opportunities to the model implementation and perfection. Besides, we observed an increasing interest stream of NLSCG relevant studies recently, presenting quite various technical schools. However, many studies are bound to specific datasets with customization issues, producing occasional successful solutions with tentative technical methods. There is no systematic study to explore and promote the further development of this field. We carried out a systematic literature survey and tool research to find potential improvement directions. First, we position the role of NLSCG among various SCG genres, and specify the generation context empirically via software development domain knowledge and programming experiences; second, we explore the selected studies collected by a thoughtfully designed snowballing process, clarify the NLSCG field and understand the NLSCG problem, which lays a foundation for our subsequent investigation. Third, we model the research problems from technical focus and adaptive challenges, and elaborate insights gained from the NLSCG research backlog. Finally, we summarize the latest technology landscape over the transformation model and depict the critical tactics used in the essential components and their correlations. This research addresses the challenges of bridging the gap between natural language processing and source code analytics, outlines different dimensions of NLSCG research concerns and technical utilities, and shows a bounded technical context of NLSCG to facilitate more future studies in this promising area.
Lifestyle Habits and Exposure to BPA and Phthalates in Women of Childbearing Age from Northern Italy: A Pilot Study

Background: Endocrine-disrupting chemicals (EDCs) are compounds that interfere with aspects of hormonal signaling. Considerable attention has been paid to their biological effects especially in women of childbearing age or during pregnancy as EDCs have been reported to cross the placenta becoming concentrated in the fetus’ circulation. Lifestyle habits, daily consumption of packaged foods and use of healthcare/cosmetic products are associated with increased EDCs levels. This cross-sectional research examined the EDCs levels and the lifestyle determinants of EDC exposure in a cohort of reproductive-age women from Northern Italy. Methods: Forty-five women (median age: 36, IQR: 30–38) were evaluated for urinary bisphenol A (BPA) and phthalates levels and also studied for EDCs’ major determinants of daily exposure; food frequency/dietary, physical activity, smoking habits and weight status. Results: Although 100% of women seemed to have been exposed to common sources of EDCs, they reported a healthy lifestyle. The multivariable model described a positive and significant association between consumption of sauces/dressings in plastic containers and monoethyl phthalate exposure (p = 0.037). Conclusions: Since reproductive age encompasses a critical window for future health and functioning of the “mothers-to-be” and their children, future studies on prenatal dietary BPA and phthalate exposure and the role of consumer product choices in reducing such exposure are recommended.
Stability of Class II Malocclusion Treatment with the Austro Repositioner Followed by Fixed Appliances in Brachyfacial Patients

One of the goals of functional-appliance devices is to modify the vertical growth pattern, solving several kinds of malocclusion. This study aimed to evaluate Class II malocclusion treatment’s stability with Austro Repositioner, followed by fixed appliances, and assess its capacity to modify vertical dimensions in brachyfacial patients. A test group of 30 patients (16 boys and 14 girls, mean 11.9 years old) with Class II malocclusion due to mandibular retrognathism and brachyfacial pattern treated with Austro Repositioner and fixed appliance were compared to a matched untreated Class II control group of 30 patients (17 boys and 13 girls, mean age 11.7 years old). Lateral cephalograms were taken at T1 (initial records), T2 (end of treatment), and T3 (one year after treatment). Statistical comparisons were performed with a paired-sample t-test and two-sample t-tests. Significant improvements in the skeletal Class II relationship were observed in the treated group. The ANB angle decreased (4.75°), the SNB angle increased (3.92°), and the total mandibular length (Co-Pg) increased (8.18 mm) (p < 0.001). Vertical dimensions were also significantly modified, the FMA angle increased (3.94°), LAFH-distance increased (3.15 mm), and overbite decreased (3.35 mm). These changes remained stable one year after treatment. The Austro Repositioner was adequate for treating the skeletal Class II malocclusion resulting from the mandible retrusion in brachyfacial patients.
3D/4D Printing of Polymers: Fused Deposition Modelling (FDM), Selective Laser Sintering (SLS), and Stereolithography (SLA)

Additive manufacturing (AM) or 3D printing is a digital manufacturing process and offers virtually limitless opportunities to develop structures/objects by tailoring material composition, processing conditions, and geometry technically at every point in an object. In this review, we present three different early adopted, however, widely used, polymer-based 3D printing processes; fused deposition modelling (FDM), selective laser sintering (SLS), and stereolithography (SLA) to create polymeric parts. The main aim of this review is to offer a comparative overview by correlating polymer material-process-properties for three different 3D printing techniques. Moreover, the advanced material-process requirements towards 4D printing via these print methods taking an example of magneto-active polymers is covered. Overall, this review highlights different aspects of these printing methods and serves as a guide to select a suitable print material and 3D print technique for the targeted polymeric material-based applications and also discusses the implementation practices towards 4D printing of polymer-based systems with a current state-of-the-art approach.
The Effect of Pets on Human Mental Health and Wellbeing during COVID-19 Lockdown in Malaysia

Simple Summary Pets are an integrative part of everyday life. Understanding the impact that pets have on human mental health and wellbeing, especially during periods of prolonged social isolation, is vitally important to determine whether animals can be integrated in prevention, recovery and intervention programmes to promote mental health and wellbeing. Research, with Western samples, suggests a positive impact of pets on humans; however, there is a lack of research on the effects of human–animal interactions in Southeast Asia. The aim of this study was to address this gap and to explore whether and how pets impact mental health and wellbeing in Malaysia during the COVID-19 induced movement control order (MCO). Additionally, the study explored if there was any interaction between other demographics, like age, gender, education, and pet ownership when it comes to mental health and wellbeing. The results show that in comparisons with people without animals, pet owners had significantly higher levels of mental wellbeing, in that they felt they could cope better with adverse situations and experienced significantly more positive emotions during the lockdown. On the other hand, there were no differences in levels of depression, stress, resilience, anxiety and negative emotions between the two participant groups. These results indicate that although the information about human–animal interaction is limited in Malaysia, pets can have a positive impact on some aspects of mental health and wellbeing and be actively integrated into promoting mental health and wellbeing in situations where people are socially isolated and experiencing difficulties coping with adversities or negative emotions. Abstract The adverse impact of SARS-CoV-2 (COVID-19) on mental and physical health has been witnessed across the globe. Associated mental health and wellbeing issues include stress, social isolation, boredom, and anxiety. Research suggests human–animal interactions may improve the overall wellbeing of an individual. However, this has been less explored in Southeast Asian countries like Malaysia and the present study examined the effect of pets on the mental health and wellbeing of Malaysians during the lockdown, or movement control order (MCO), due to COVID-19 pandemic. A cross-sectional survey was carried out, with 448 Malaysian participants, who completed online assessments for psychological outcomes, psychological wellbeing, positive–negative emotions, resilience, and coping self-efficacy. Results indicate that pet owners reported significantly better coping self-efficacy, significantly more positive emotions, and better psychological wellbeing, but contrary to expectations, there was no differences on other measures. Among pet owners, cat owners reported more positive emotions and greater wellbeing than dog owners. The results show that that pets have some impact on improved psychological health of their owners and could be integrated into recovery frameworks for promoting mental health and wellbeing.
The Risk of Clostridioides difficile Infection in Cirrhotic Patients Receiving Norfloxacin for Secondary Prophylaxis of Spontaneous Bacterial Peritonitis—A Real Life Cohort

Background and Objectives: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis. Antibiotic prophylaxis is effective but can lead to an increased incidence of Clostridioides difficile infection (CDI). The aim of this study was to evaluate the incidence of CDI and the risk factors in cirrhotic patients with a previous episode of SBP receiving norfloxacin as secondary prophylaxis. Materials and Methods: We performed a prospective, cohort study including patients with liver cirrhosis and SBP, successfully treated over a 2-year period in a tertiary university hospital. All the patients received secondary prophylaxis for SBP with norfloxacin 400 mg/day. Results: There were 122 patients with liver cirrhosis and SBP included (mean age 57.5 ± 10.8 years, 65.5% males). Alcoholic cirrhosis was the major etiology accounting for 63.1% of cases. The mean MELD score was 19.7 ± 6.1. Twenty-three (18.8%) of all patients developed CDI during follow-up, corresponding to an incidence of 24.8 cases per 10,000 person-years. The multivariate Cox regression analysis demonstrated that alcoholic LC etiology (HR 1.40, 95% CI 1.104–2.441, p = 0.029) and Child-Pugh C class (HR 2.50, 95% CI 1.257–3.850, p = 0.034) were independent risk factors for CDI development during norfloxacin secondary prophylaxis. The development of CDI did not influence the mortality rates in cirrhotic patients with SBP receiving norfloxacin. Conclusions: Cirrhotic patients with SBP and Child-Pugh C class and alcoholic liver cirrhosis had a higher risk of developing Clostridioides difficile infection during norfloxacin secondary prophylaxis. In patients with alcoholic Child-Pugh C class liver cirrhosis, alternative prophylaxis should be evaluated as SBP secondary prophylaxis.
Promoter Hypermethylation Promotes the Binding of Transcription Factor NFATc1, Triggering Oncogenic Gene Activation in Pancreatic Cancer

Simple Summary High promoter methylation is not necessarily associated with shutting down gene activity but does sometimes correlate with increased transcription instead. In a genome-wide analysis, we studied gene regulation in pancreatic cancer. We identified a substantial number of genes with both promoter hypermethylation and high transcription levels. Subsequently, we screened for transcription factors that exhibit specific binding to such hypermethylated sequences. NFATc1 was one of several transcription factors that bound specifically methylated DNA motifs and triggered transcription. A particularly affected gene was ALDH1H3, whose expression has strong oncogenic implications. Activation of ALDH1H3 was due to a direct regulative process involving NFATc1 binding to its hypermethylated promoter. The results provide insights into the activation of gene transcription that is promoted by DNA methylation. Abstract Studies have indicated that some genes involved in carcinogenesis are highly methylated in their promoter regions but nevertheless strongly transcribed. It has been proposed that transcription factors could bind specifically to methylated promoters and trigger transcription. We looked at this rather comprehensively for pancreatic ductal adenocarcinoma (PDAC) and studied some cases in more detail. Some 2% of regulated genes in PDAC exhibited higher transcription coupled to promoter hypermethylation in comparison to healthy tissue. Screening 661 transcription factors, several were found to bind specifically to methylated promoters, in particular molecules of the NFAT family. One of them—NFATc1—was substantially more strongly expressed in PDAC than control tissue and exhibited a strong oncogenic role. Functional studies combined with computational analyses allowed determining affected genes. A prominent one was gene ALDH1A3, which accelerates PDAC metastasis and correlates with a bad prognosis. Further studies confirmed the direct up-regulation of ALDH1A3 transcription by NFATc1 promoter binding in a methylation-dependent process, providing insights into the oncogenic role of transcription activation in PDAC that is promoted by DNA methylation.
Ophelimus bipolaris sp. n. (Hymenoptera, Eulophidae), a New Invasive Eucalyptus Pest and Its Host Plants in China

Simple Summary Eucalyptus species have become one of the most commonly planted trees worldwide, including China. However, the productivity of Eucalyptus plantations has been threatened by the recent increase of invasive insect pests. Gall inducers of the genus Ophelimus (Eulophidae) are among the most important invasive species in Eucalyptus plantations. Based on the combined analysis of biological, morphological and molecular evidence, we here describe a new invasive species, Ophelimus bipolaris sp. n. , from China. This wasp induces galls only on the leaf blade surface of four Eucalyptus species. It can complete a life cycle on E. urophylla in approximately 2 months under local climatic conditions in Guangzhou, China. Abstract Eucalyptus species have become one of the most commonly planted trees worldwide, including China, due to their fast growth and various commercial applications. However, the productivity of Eucalyptus plantations has been threatened by exotic invasive insect pests in recent years. Among these pests, gall inducers of the genus Ophelimus of the Eulophidae family are among the most important invasive species in Eucalyptus plantations. We report here for the first time the presence of a new invasive Eucalyptus gall wasp, Ophelimus bipolaris sp. n. , in Guangzhou, China, which also represents the first species of the genus reported from China. The identity of the new species was confirmed by an integrative approach combing biological, morphological and molecular evidence. The new species is described and illustrated. This wasp induces galls only on the leaf blade surface of four Eucalyptus species: E. grandis, E. grandis × E. urophylla, E. tereticornis and E. urophylla. Our preliminary observation showed that O. bipolaris could complete a life cycle on E. urophylla in approximately 2 months under local climatic conditions (23.5–30 °C). Considering the severe damage it may cause to Eucalyptus production, further investigations of its biology and control are urgently needed in China.
Research and Clinical Landscape of Bispecific Antibodies for the Treatment of Solid Malignancies

Solid tumors adopt multiple mechanisms to grow, evade immune responses, and to withstand therapeutic approaches. A major breakthrough in the armamentarium of anti-cancer agents has been the introduction of monoclonal antibodies (mAbs), able to inhibit aberrantly activated pathways and/or to unleash antigen (Ag)-specific immune responses. Nonetheless, mAb-mediated targeted pressure often fails due to escape mechanisms, mainly Ag loss/downregulation, ultimately providing therapy resistance. Hence, in order to target multiple Ag at the same time, and to facilitate cancer-immune cells interactions, bispecific antibodies (bsAbs) have been developed and are being tested in clinical trials, yielding variable safety/efficacy results based on target selection and their structure. While in hematologic cancers the bsAb blinatumomab recently reached the Food and Drug Administration (FDA)-approval for B Cell Acute Lymphoblastic Leukemia, bsAbs use in solid tumors faces considerable challenges, such as target Ag selection, biodistribution, and the presence of an immune-suppressive tumor microenvironment (TME). This review will focus on the state-of-the art, the design, and the exploitation of bsAbs against solid malignancies, delineating their mechanisms of action, major pitfalls, and future directions.