Miracle-dz/UniFAR-FTUs huggingface dataset:
Toward the Proactive Design of Sustainable Chemicals: Ionic Liquids as a Prime Example.

The tailorable and often unique properties of ionic liquids (ILs) drive their implementation into a broad variety of seminal technologies. The modular design of ILs allows in this context a proactive selection of structures that favor environmental sustainability-ideally without compromising their technological performance. To achieve this objective, the whole life cycle must be taken into account and various aspects considered simultaneously. In this review, we discuss how the structural design of ILs affects their environmental impacts throughout all stages of their life cycles and scrutinize the available data in order to point out knowledge gaps that need further research activities. The design of more sustainable ILs starts with the selection of the most beneficial precursors and synthesis routes, takes their technical properties and application specific performance into due account, and considers its environmental fate particularly in terms of their (eco)toxicity, biotic and abiotic degradability, mobility, and bioaccumulation potential. Special emphasis is placed on reported structure-activity relationships and suggested mechanisms on a molecular level that might rationalize the empirically found design criteria.
Hypothyroidism induced by propylthiouracil decrease sirtuin1 content in rat heart

Background: In this study, the changes in sirtuin1 (SIRT1) levels in the heart of rats with hypothyroidism (HT) were evaluated. Methods: A total of 20 Wistar male rats were randomly divided into control groups (n=10) and HT groups (n=10). In the HT groups, we used 0.05% propylthiouracil (PTU) saline solution to prepare the HT model, while 0.9% sodium chloride solution was used as a placebo in the control groups. During the intervention period, the body weight of rats was measured weekly, and serum triiodothyronine (TT 3 ), tetraiodothyronine (TT 4 ), thyroid-stimulating hormone (TSH), body weight, heart weight, and SIRT1 content in the heart were measured after intervention. We compared the differences in SIRT1 content between the two groups and analyzed the correlation between SIRT1 and thyroid hormone concentrations. Results: After 8 weeks of intervention, the HT rat model was successfully produced. The body weight of the HT group rats increased more slowly than that of the control groups. The heart weight of the HT groups was significantly lower than that of the control groups, and SIRT1 content decreased significantly compared to in control group rats. However, there were no significant differences between the two groups in heart weight index. The relative content of SIRT1 was significantly correlated with TT3 concentrations, both in the control group and HT group. Conclusions: Our results suggest that HT induced by PTU significantly reduces myocardial SIRT1 content. Decreased TT3 was significantly associated with decreased SIRT1 content.
DNA Repair in Staphylococcus aureus

Staphylococcus aureus is a common cause of both superficial and invasive infections of humans and animals. Despite a potent host response and apparently appropriate antibiotic therapy, staphylococcal infections frequently become chronic or recurrent, demonstrating a remarkable ability of S. aureus to withstand the hostile host environment. SUMMARY Staphylococcus aureus is a common cause of both superficial and invasive infections of humans and animals. Despite a potent host response and apparently appropriate antibiotic therapy, staphylococcal infections frequently become chronic or recurrent, demonstrating a remarkable ability of S. aureus to withstand the hostile host environment. There is growing evidence that staphylococcal DNA repair makes important contributions to the survival of the pathogen in host tissues, as well as promoting the emergence of mutants that resist host defenses and antibiotics. While much of what we know about DNA repair in S. aureus is inferred from studies with model organisms, the roles of specific repair mechanisms in infection are becoming clear and differences with Bacillus subtilis and Escherichia coli have been identified. Furthermore, there is growing interest in staphylococcal DNA repair as a target for novel therapeutics that sensitize the pathogen to host defenses and antibiotics. In this review, we discuss what is known about staphylococcal DNA repair and its role in infection, examine how repair in S. aureus is similar to, or differs from, repair in well-characterized model organisms, and assess the potential of staphylococcal DNA repair as a novel therapeutic target.
Inverse Reinforcement Q-Learning Through Expert Imitation for Discrete-Time Systems

In inverse reinforcement learning (RL), there are two agents. An expert target agent has a performance cost function and exhibits control and state behaviors to a learner. The learner agent does not know the expert’s performance cost function but seeks to reconstruct it by observing the expert’s behaviors and tries to imitate these behaviors optimally by its own response. In this article, we formulate an imitation problem where the optimal performance intent of a discrete-time (DT) expert target agent is unknown to a DT Learner agent. Using only the observed expert’s behavior trajectory, the learner seeks to determine a cost function that yields the same optimal feedback gain as the expert’s, and thus, imitates the optimal response of the expert. We develop an inverse RL approach with a new scheme to solve the behavior imitation problem. The approach consists of a cost function update based on an extension of RL policy iteration and inverse optimal control, and a control policy update based on optimal control. Then, under this scheme, we develop an inverse reinforcement Q-learning algorithm, which is an extension of RL Q-learning. This algorithm does not require any knowledge of agent dynamics. Proofs of stability, convergence, and optimality are given. A key property about the nonunique solution is also shown. Finally, simulation experiments are presented to show the effectiveness of the new approach.
Adolescent Health on Social Media and the Mentorship of Youth Investigators: Five Content Analysis Studies Conducted by Youth Investigators

Although the literature on adolescent health includes studies that incorporate youth perspectives via a participatory design, research that is designed, conducted, and presented by youth remains absent. This paper presents the work of 5 youth investigators on the intersecting topics of adolescent health and social media. Each of these youths was equipped with tools, knowledge, and mentorship for scientifically evaluating a research question. The youths developed a research question that aligned with their interests and filled a gap that they identified in the literature. The youths, whose projects are featured in this paper, designed and conducted their own research project, drafted their own manuscript, and revised and resubmitted a draft based on reviewer input. Each youth worked with a research mentor; however, the research questions, study designs, and suggestions for future research were their own.
High‐resolution analysis of the conformational transition of pro‐apoptotic Bak at the lipid membrane

Permeabilization of the outer mitochondrial membrane by pore‐forming Bcl2 proteins is a crucial step for the induction of apoptosis. Despite a large set of data suggesting global conformational changes within pro‐apoptotic Bak during pore formation, high‐resolution structural details in a membrane environment remain sparse. Here, we used NMR and HDX‐MS (Hydrogen deuterium exchange mass spectrometry) in lipid nanodiscs to gain important high‐resolution structural insights into the conformational changes of Bak at the membrane that are dependent on a direct activation by BH3‐only proteins. Furthermore, we determined the first high‐resolution structure of the Bak transmembrane helix. Upon activation, α‐helix 1 in the soluble domain of Bak dissociates from the protein and adopts an unfolded and dynamic potentially membrane‐bound state. In line with this finding, comparative protein folding experiments with Bak and anti‐apoptotic BclxL suggest that α‐helix 1 in Bak is a metastable structural element contributing to its pro‐apoptotic features. Consequently, mutagenesis experiments aimed at stabilizing α‐helix 1 yielded Bak variants with delayed pore‐forming activity. These insights will contribute to a better mechanistic understanding of Bak‐mediated membrane permeabilization.
Validity Evidence for Procedure-specific Competence Assessment Tools in General Surgery

Supplemental Digital Content is available in the text Objective: This study aims to provide a focused and detailed assessment of the validity evidence supporting procedure-specific operative assessment tools in general surgery. Summary of Background Data: Competency-based assessment tools should be supported by robust validity evidence to be used reliably for evaluation of operative skills. The contemporary framework of validity relies on five sources of evidence: content, response process, internal structure, relation to other variables, and consequences. Methods: A systematic search of 8 databases was conducted for studies containing procedure-specific operative assessment tools in general surgery. The validity evidence supporting each tool was assessed and scored in alignment with the contemporary framework of validity. Methodological rigour of studies was assessed with the Medical Education Research Study Quality Instrument. The educational utility of each tool was assessed with the Accreditation Council for Graduate Medical Education framework. Results: There were 28 studies meeting inclusion criteria and 23 unique tools were assessed. Scores for validity evidence varied widely between tools, ranging from 3 – 14 (maximum 15). Medical Education Research Study Quality Instrument scores assessing the quality of study methodology were also variable (8.5–15.5, maximum 16.5). Direct reporting of educational utility criteria was limited. Conclusions: This study has identified a small group of procedure-specific operative assessment tools in general surgery. Many of these tools have limited validity evidence and have not been studied sufficiently to be used reliably in high-stakes summative assessments. As general surgery transitions to competency-based training, a more robust library of operative assessment tools will be required to support resident education and evaluation.
Optical coherence tomography monitoring and diagnosing retinal changes in multiple sclerosis

This study explores the use of optical coherence tomography (OCT) to monitor and diagnose multiple sclerosis (MS). The analysis of reduced total macular volume and peripapillary retinal nerve fiber layer thinning are shown. The severity of these defects increases as MS progresses, reflecting the progressive degeneration of nerve fibers and retinal ganglion cells. The OCT parameters are noninvasive, sensitive indicators that can be used to assess the progression of neurodegeneration and inflammation in MS.
Time-Varying Association Between Severe Respiratory Syncytial Virus Infections and Subsequent Severe Asthma and Wheeze and Influences of Age at the Infection.

BACKGROUND Early-life severe respiratory syncytial virus (RSV) infection has been associated with subsequent risk of asthma and recurrent wheeze. However, changes in the association over time and the interaction effect of the age at first RSV infection are less well understood. We aimed to assess the time-varying association between RSV and subsequent asthma and wheeze admission and explore how the association was affected by the age at RSV infection. METHODS We retrospectively followed up a cohort of 23 365 children for a median of 6.9 years using Scottish health databases. Children who were born between 2001 and 2013 and had RSV-associated respiratory tract infection (RTI) admissions under 2 years were in the exposed group; those with unintentional accident admissions under 2 years comprised the control group. The Cox proportional-hazards model was used to report adjusted hazard ratios (HRs) of RSV admissions on subsequent asthma and wheeze admissions. We did subgroup analyses by follow-up years. We also explored how this association was affected by the age at first RSV admission. RESULTS The association was strongest in the first 2 years of follow-up and decreased over time. The association persisted for 6 years in children whose first RSV-RTI admission occurred at 6-23 months of age, with an adjusted HR of 3.9 (95% confidence interval [CI], 3.1-4.9) for the first 2 years, 2.3 (95% CI, 1.6-3.2) for 2 to <4 years, and 1.9 (95% CI, 1.2-2.9) for 4 to <6 years of follow-up. In contrast, the association was only significant for the first 2 years after first RSV-RTI admissions occurring at 0-5 months. CONCLUSIONS We found a more persistent association for subsequent asthma and wheeze in children whose first severe RSV infection occurred at 6-23 months compared to those whose first severe RSV infection occurred at 0-6 months. This provides new evidence for further assessment of the association and RSV intervention programs.
The Thioesterase ACOT1 as a Regulator of Lipid Metabolism in Type 2 Diabetes Detected in a Multi-Omics Study of Human Liver

Type 2 diabetes (T2D) is characterized by pathophysiological alterations in lipid metabolism. One strategy to understand the molecular mechanisms behind these abnormalities is to identify cis-regulatory elements (CREs) located in chromatin-accessible regions of the genome that regulate key genes. In this study we integrated assay for transposase-accessible chromatin followed by sequencing (ATAC-seq) data, widely used to decode chromatin accessibility, with multi-omics data and publicly available CRE databases to identify candidate CREs associated with T2D for further experimental validations. We performed high-sensitive ATAC-seq in nine human liver samples from normal and T2D donors, and identified a set of differentially accessible regions (DARs). We identified seven DARs including a candidate enhancer for the ACOT1 gene that regulates the balance of acyl-CoA and free fatty acids (FFAs) in the cytoplasm. The relevance of ACOT1 regulation in T2D was supported by the analysis of transcriptomics and proteomics data in liver tissue. Long-chain acyl-CoA thioesterases (ACOTs) are a group of enzymes that hydrolyze acyl-CoA esters to FFAs and coenzyme A. ACOTs have been associated with regulation of triglyceride levels, fatty acid oxidation, mitochondrial function, and insulin signaling, linking their regulation to the pathogenesis of T2D. Our strategy integrating chromatin accessibility with DNA binding and other types of omics provides novel insights on the role of genetic regulation in T2D and is extendable to other complex multifactorial diseases.
Collateral effects of deletion of nlpD on rpoS and rpoS-dependent genes. Reply.

The authors reply: In their Letter to the Editor, Tsunoi et al. (1) discuss a very interesting and relevant aspect of our published work (2) and suggest topics for further investigation. This published study identifies the E. coli NlpD protein as a potent regulator of gene expression in human cells. This effect is attributed to the inhibition of RNA polymerase II phosphorylation (Pol II), mediated, in part, by effects of NlpD on the Pol II RPB1 subunit and PAF1C (2, 3). The discovery of the NlpD effect was made possible by the isolation of a loss-of-function mutant (SN25) from a human carrier of the parent strain E. coli 83972, and a mutation strategy was devised to introduce the nlpD point mutation from SN25 into the parent strain and to complement SN25 with a fully functional nlpD gene cluster. To address whether NlpD exerts its effects on host cells independently or in synergy with sigma38 (σ38), the 5′nlpD coding sequence was deleted in E. coli 83972, while leaving the rpoS promoter intact. The partial nlpD deletion mutant lost the ability to inhibit PAF1C and Pol II phosphorylation. In the E. coli genome, nlpD and rpoS form an operon. σ38 expression is regulated, in part, from a promoter located within nlpD. Elegant studies addressing the role of σ38 as a global regulator [. ] Letter to the Editor Infectious disease
The Effect of Very Low Concentrations of Ethanol on Microvascular Artery and Vein Anastomosis: An Experimental Study

Abstract Objectives This study investigated the effect of very low concentrations of ethanol on artery and vein anastomosis. Also, it was aimed to determine the appropriate ethanol concentration to be used in vasospasm. Methods Rats were divided into five groups of eight rats, each group, as follows: Group i: saline; Group ii: 2.5% ethanol; Group iii: 5% ethanol; Group IV: 7.5% ethanol; and Group V: 10% ethanol. During the femoral artery and vein anastomosis, 1ml of the agent was used for irrigation in each group. Vessel diameters were measured before the anastomosis, at the fifth and 15th minutes, and the third week after the anastomosis. Histopathological samples were taken in the third week. Results In Groups ii and iii, the mean vessel diameters were found to increase 15th minute. Also observed was an increase in mean vessel diameter that continued in the third week. Although acute vasodilation was detected in Groups IV and V, arterial and venous thrombosis was observed in the third week. Intima and media thickness decreased in Group ii, while it increased in Group iii. Perivascular inflammation and fibrosis increased as the ethanol concentration increased. Conclusion 2.5% ethanol causes acute and prolonged vasodilation and does not cause endothelial cell damage, perivascular inflammation, and fibrosis. 2.5% ethanol will be a powerful alternative use in many situations that occur with vasospasm.
Liquid biopsy of cerebrospinal fluid for MYD88 L265P mutation is useful for diagnosis of central nervous system lymphoma

The current standard of diagnosing central nervous system (CNS) lymphoma is stereotactic biopsy, however the procedure has a risk of surgical complication. Liquid biopsy of the CSF is a less invasive, non‐surgical method that can be used for diagnosing CNS lymphoma. In this study, we established a clinically applicable protocol for determining mutations in MYD88 in the CSF of patients with CNS lymphoma. CSF was collected prior to the start of chemotherapy from 42 patients with CNS lymphoma and matched tumor specimens. Mutations in MYD88 in 33 tumor samples were identified using pyrosequencing. Using 10 ng each of cellular DNA and cell‐free DNA (cfDNA) extracted from the CSF, the MYD88 L265P mutation was detected using digital PCR. The conditions to judge mutation were rigorously determined. The median Target/Total value of cases with MYD88 mutations in the tumors was 5.1% in cellular DNA and 22.0% in cfDNA. The criteria to judge mutation were then determined, with a Target/Total value of 0.25% as the cutoff. When MYD88 mutations were determined based on these criteria, the sensitivity and specificity were 92.2% and 100%, respectively, with cellular DNA; and the sensitivity and specificity were 100% with cfDNA. Therefore, the DNA yield, mutated allele fraction, and accuracy were significantly higher in cfDNA compared with that in cellular DNA. Taken together, this study highlights the importance of detecting the MYD88 L265P mutation in cfDNA of the CSF for diagnosing CNS lymphoma using digital PCR, a highly accurate and clinically applicable method.
The PdeK-PdeR two-component system promotes unipolar localization of FimX and pilus extension in Xanthomonas oryzae pv. oryzicola

Description A two-component system in a plant pathogen degrades c-di-GMP to promote pilus extension and virulence. Lengthening pili with c-di-GMP turnover Bacterial type IV pili (T4P) are polar appendages that mediate twitching motility and contribute to virulence. Low intracellular concentrations of the second messenger cyclic di-GMP (c-di-GMP) induce T4P extension, which depends on the c-di-GMP–binding protein FimX and its association with the T4P assembly complex. Wei et al. found that a two-component system consisting of the histidine kinase PdeK and its downstream effector, the phosphodiesterase PdeR, promoted T4P extension and virulence in the rice pathogen Xanthomonas oryzae pv. oryzicola by degrading c-di-GMP and mediating the unipolar localization of FimX. These findings link PdeR-mediated degradation of c-di-GMP to FimX-dependent pilus extension. Bacterial type IV pili (T4P) contribute to virulence and can be rapidly extended and retracted to mediate twitching motility. T4P biogenesis, which is normally limited to the cell poles, is regulated by extracellular stimuli and internal signals such as cyclic di-GMP (c-di-GMP). The c-di-GMP–binding protein FimX interacts with the T4P assembly complex and, when intracellular c-di-GMP concentrations are low, assumes a unipolar localization and promotes T4P biogenesis. Here, we demonstrated that FimX formed a complex with the two-component system consisting of the histidine kinase PdeK and its downstream response regulator PdeR. This complex promoted T4P assembly in the phytopathogen Xanthomonas oryzae pv. oryzicola and virulence in rice. PdeK and the c-di-GMP phosphodiesterase activity of PdeR were required for the unipolar localization of FimX, leading to T4P extension. High amounts of c-di-GMP reduced the affinity of FimX for PdeR in vitro, consistent with FimX promoting T4P extension only under conditions of low c-di-GMP. We propose that low intracellular amounts of c-di-GMP created by PdeR facilitate the recruitment of FimX to the leading pole of motile cells. Our findings indicate that the PdeK-PdeR two-component system connects environmental cues to second messenger turnover, resulting in a change in the intracellular concentration of c-di-GMP that promotes T4P biogenesis and virulence.
LncRNA HCG18 suppresses CD8+ T cells to confer resistance to cetuximab in colorectal cancer via miR-20b-5p/PD-L1 axis.

Aim: We aimed to explore the effect of long noncoding RNA HCG18 in colorectal cancer (CRC). Materials & methods: Relative gene and protein expression were screened. Colony formation and flow cytometry assays were performed to determine proliferation and apoptosis. Dual luciferase assay and RNA immunoprecipitation assay were conducted to validate the interaction between indicated molecules. Xenograft in nude mice was applied to verify the conclusion in vivo. Results: HCG18 and PD-L1 were upregulated while miR-20b-5p was downregulated in CRC tissue. Functional analysis revealed that lncRNA HCG18 promoted proliferation, migration and resistance to cetuximab of CRC cells via miR-20b-5p/PD-L1 axis. Conclusion: HCG18 facilitated the progress of tumor, conferred to cetuximab resistance and suppressed CD8+ T cell via miR-20b-5p/PD-L1 axis.
Ocular adnexal lymphoma: an updated review of pathogenesis, diagnosis, and treatment.

Lymphoma is the most common primary tumor of the orbit, accounting for 55% of all orbital malignancies. When divided into histopathological subtypes, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises the largest proportion. Clinical manifestations are unspecific, but in patients with slow-growing painless orbital mass, or red conjunctival lesion suggestive of 'salmon patch', ocular adnexa lymphoma (OAL) should be suspected. Although the pathogenetic mechanism of ocular adnexal MALT lymphoma (OAML) is not yet fully understood, the relationship between OAML and Chlamydia psittaci has been hypothesized recently, similar to that between gastric MALT lymphoma and Helicobacter pylori. This suggests a new treatment option for OAML; bacterial eradication therapy with systemic antibiotics. Several other treatment methods for OAML have been introduced, but no treatment guidelines have been established yet. In this article, we summarize the current knowledge on the clinical features, pathogenesis, diagnostic methods, therapeutic strategies, and prognosis of OAML.