Miracle-dz/UniFAR-FTUs huggingface dataset:
Colonization of Clostridium butyricum in Rats and Its Effect on Intestinal Microbial Composition

Gut microorganisms participate in many physiological processes. In particular, Clostridium butyricum can modulate gut microorganisms and treat diseases. The colonization and persistence of strains in the gut contribute to beneficial effects, and the colonization by C. butyricum in the gut is currently unknown. We investigated the total intestinal contents of C. butyricum at 12 h, 24 h, 48 h, and four and six days using real-time reverse transcription-PCR, after oral administration of C. butyricum to rats for seven consecutive days. We assessed the bacterial community structure using Illumina MiSeq sequencing. The results showed that C. butyricum was mainly colonized in the colon. The total content of C. butyricum in the gut increased significantly at 12 h after administration. Exogenous C. butyricum could still be detected in the gut six days after administration. Administration of C. butyricum significantly enhanced gut microbial diversity. The relative abundance of short-chain fatty acid-producing bacterial genera was shown to be higher than that of the control group, and treatment with C. butyricum elevated Firmicutes and diminished Bacteroidetes phyla compared with to the control group. These findings laid the foundation for the study of probiotic colonization capacity and the improvement of microflora for the prevention of gut diseases.
Optogenetic Activation of V1 Interneurons Reveals the Multimodality of Spinal Locomotor Networks in the Neonatal Mouse

In the spinal cord, classes of interneurons have been studied in vitro to determine their role in producing or regulating locomotion. It is unclear whether all locomotor behaviors are produced by the same circuitry or engage different subsets of neurons. Here, in neonatal mice of either sex, we test this idea by comparing the actions of a class of spinal, inhibitory interneuron (V1) expressing channelrhodopsin driven by the engrailed-1 transcription factor on the rhythms elicited by different methods. We find that, although the overall locomotor activities in vitro are similar, V1 interneuron depolarization produces opposite effects depending of the mode of activation of the locomotor circuitry. The differential behavior of V1 neurons suggests that their function depends on how the locomotor rhythm is activated and is consistent with the idea that the functional organization of the corresponding locomotor networks also differs. SIGNIFICANCE STATEMENT The neural networks dictating the execution of fictive locomotion are located in the spinal cord. It is generally assumed that the mode of activation of these spinal networks should not change the recruitment or function of neurons. Here, we manipulated the activity of a class of interneuron (V1), which targets these networks and found that their activation induces opposite effects depending on the mode of activation. This suggests that the mode of activation of the spinal networks differentially recruits either V1 interneurons or other interneurons, or both.
Changes of DNA Damage Effect of T-2 or Deoxynivalenol Toxins during Three Weeks Exposure in Common Carp (Cyprinus carpio L.) Revealed by LORD-Q PCR

The present study aimed to adapt a Long-run Real-time DNA Damage Quantification (LORD-Q) qPCR-based method for the analysis of the mitochondrial genome of Common carp (Cyprinus carpio L.) and detect the DNA damaging effect of T-2 (4.11 mg kg−1) and deoxynivalenol (5.96 mg kg−1) mycotoxins in a 3-week feeding period. One-year-old Common carp were treated in groups (control, T-2 and DON). The mycotoxins were sprayed over the complete pelleted feed, and samples were taken weekly. Following the adaptation of LORD-Q PCR method for the Common carp species, the number of lesions were calculated to determine the amount of DNA damage. In the first and second weeks, the T-2 and the DON treated groups differed significantly from each other; however these differences disappeared in the third week. There was a significant difference in the DNA lesion values between weeks 1 and 3 in the deoxynivalenol-contaminated groups. While in the T-2 treated groups, the DNA lesion values were significantly reduced on weeks 2 and 3 compared to week 1. The results suggested that the trichothecene mycotoxins have a relevant DNA damaging effect.
A plant lipocalin promotes retinal-mediated oscillatory lateral root initiation

Description Building a wider root network As roots grow through the soil, lateral branches develop to broaden the reach toward water and nutrients. Just where on the main root these lateral roots will develop is organized by an oscillatory root clock. Dickinson et al. have now identified an initiating signal in the form of the signaling molecule retinal. Oscillatory expression of a retinal-binding protein, a temperature-sensitive lipocalin, defines sites where retinal signals can initiate growth. —PJH Retinal signaling translates location into lateral root organogenesis. In Arabidopsis, de novo organogenesis of lateral roots is patterned by an oscillatory mechanism called the root clock, which is dependent on unidentified metabolites. To determine whether retinoids regulate the root clock, we used a chemical reporter for retinaldehyde (retinal)–binding proteins. We found that retinal binding precedes the root clock and predicts sites of lateral root organogenesis. Application of retinal increased root clock oscillations and promoted lateral root formation. Expression of an Arabidopsis protein with homology to vertebrate retinoid-binding proteins, TEMPERATURE INDUCED LIPOCALIN (TIL), oscillates in the region of retinal binding to the reporter, confers retinal-binding activity in a heterologous system, and, when mutated, decreases retinal sensitivity. These results demonstrate a role for retinal and its binding partner in lateral root organogenesis.
Facilitators and Barriers for Young Medical Doctors Writing Their First Manuscript for Publication

Although scientific publication is often mandatory in medical professions, writing the first research article for publication is challenging, especially as medical curricula have only a minor focus on scientific writing. The aim was therefore to identify facilitators and barriers experienced by medical doctors writing their first scientific article for publication. An explorative inductive approach made use of semi-structured interviews for collecting data until saturation. Data were analyzed with systematic text condensation. Several barriers were identified: (a) writing in general; (b) writing in English; (c) dealing with content, structure, and presentation; and (d) navigating in the author group. Good supervision in the initial writing phase was a facilitating factor. Medical doctors requested a course in which they could work on their own articles and give feedback to fellow students. They valued skilled lecturers and individual supervision, and they wanted to learn about author instructions, how to present text correctly, and how to sell their core message. Their goal was to create a useful end product and to obtain European Credit Transfer System (ECTS) points. The facilitators and barriers that medical doctors experience when writing their first scientific article for publication and their course requests should be reflected in the learning objectives and content of future courses.
Determination of Oxidized Lipids in Commonly Consumed Foods and a Preliminary Analysis of Their Binding Affinity to PPARγ

Foods rich in poly unsaturated fatty acids (PUFA) are vulnerable to oxidation. While it is well established that endogenously derived oxidized lipids are ligands of the transcription factor PPARγ, the binding ability of diet-derived oxidized lipids is unknown. Our two-fold objective was to determine the oxidized lipid content and PPARγ binding ability of commonly consumed foods. Extracted food lipids were assayed for the peroxide value, conjugated dienes, and aldehydes, and PPARγ binding was assessed by an in vitro PPARγ ligand screening assay. Oxidized lipids were present in all foods tested at the time of purchase, and oxidation did not increase during storage. The peroxide values for walnuts, sunflower seeds, and flax meal were significantly lower at the end of three months as compared to the day of purchase (peroxide value: 1.26 ± 0.13 vs. 2.32 ± 0.4; 1.65 ± 0.23 vs. 2.08 ± 0.09; 3.07 ± 0.22 vs. 9.94 ± 0.75 mEq/kg fat, p ≤ 0.05, respectively). Lipids extracted from French fries had the highest binding affinity (50.87 ± 11.76%) to PPARγ compared to other foods. Our work demonstrates that oxidized lipids are present in commonly consumed foods when purchased, and for the first time demonstrates that some contain ligands of PPARγ.
Characterization and Antitumoral Activity of Biohybrids Based on Turmeric and Silver/Silver Chloride Nanoparticles

The phyto-development of nanomaterials is one of the main challenges for scientists today, as it offers unusual properties and multifunctionality. The originality of our paper lies in the study of new materials based on biomimicking lipid bilayers loaded with chlorophyll, chitosan, and turmeric-generated nano-silver/silver chloride particles. These materials showed a good free radical scavenging capacity between 76.25 and 93.26% (in vitro tested through chemiluminescence method) and a good antimicrobial activity against Enterococcus faecalis bacterium (IZ > 10 mm). The anticancer activity of our developed bio-based materials was investigated against two cancer cell lines (human colorectal adenocarcinoma cells HT-29, and human liver carcinoma cells HepG2) and compared to one healthy cell line (human fibroblast BJ cell line). Cell viability was evaluated for all prepared materials after a 24 h treatment and was used to select the biohybrid with the highest therapeutic index (TI); additionally, the hemolytic activity of the samples was also evaluated. Finally, we investigated the morphological changes induced by the developed materials against the cell lines studied. Biophysical studies on these materials were done by correlating UV–Vis and FTIR absorption spectroscopy, with XRD, SANS, and SAXS methods, and with information provided by microscopic techniques (AFM, SEM/EDS). In conclusion, these “green” developed hybrid systems are an important alternative in cancer treatment, and against health problems associated with drug-resistant infections.
Normative Reference of the Single Leg, Medial Countermovement Jump in Adolescent Youth Ice Hockey Players

Functional performance tests provide quantitative information on specialized sport movements and are important for documenting training and fatigue. The single leg, medial countermovement jump provides objective measures of frontal plane force, velocity and power, and is relevant for ice hockey players given the similar lateral movement to ice skating. This study measured normative single leg, medial countermovement jump parameters (i.e., vertical and lateral maximum force, average concentric power and average concentric power during the last 100 ms) amongst male youth ice hockey players and assessed interlimb asymmetry in these healthy athletes. Ninety-one elite youth players participated in the study. Participants completed three right and three left jumps. Non-parametric tests were performed to evaluate between-jump and between-group comparisons. Many differences in jump force and power parameters were observed between the 10U/11U and 12U/13U age groups, and the 12U/13U and 14U/15U age groups, but differences were not as consistent between older or younger players. The average asymmetry index for each age group was less than 15% for force parameters, while the power parameters had larger asymmetry indices (between 9% and 22%). Our results provide age-specific reference values and asymmetry indices for male elite youth ice hockey players aged 10–18 years performing the single leg, medial countermovement jump.
Durable Lithium/Selenium Batteries Enabled by the Integration of MOF-Derived Porous Carbon and Alucone Coating

Lithium-selenium (Li-Se) batteries are a promising energy storage system in electric vehicles due to their high capacity and good kinetics. However, the shuttle effect issue, caused by polyselenide dissolution from the Se cathode, has hampered the development of Li-Se batteries. Herein, we developed a facile preparation of porous carbon from a metal-organic framework (MOF) to confine Se (Se/CZIF) and protect the Se/CZIF composite with an alucone coating by molecular layer deposition (MLD). The optimal alucone coated Se/CZIF cathode prepared exhibits a one-step reversible charge/discharge process in the carbonate electrolytes. The inhibition of polyselenide dissolution is credited with the improved electrochemical performance, formation of thin and stable solid electrolyte interphase (SEI) layers, and a reduction in charge transfer resistance, thus improving the overall performance of Li-Se batteries.
Phenolic Compounds in Whole Grain Sorghum and Their Health Benefits

Sorghum grain (Sorghum bicolor L. Moench) is a staple food grown across the globe, and is mainly cultivated in the semi-arid regions of Africa and Asia. Recently, sorghum grain is increasingly utilized for human consumption, due to the gluten-free nature and potential phenolic-induced health benefits. Sorghum grain is rich in bioactive phenolic compounds, such as ferulic acid, gallic acid, vanillic acid, luteolin, and apigenin, 3-deoxyanthocyanidins (3-DXA), which are known to provide many health benefits, including antioxidant, anti-inflammatory, anti-proliferative, anti-diabetic, and anti-atherogenic activities. Given an increasing trend of sorghum consumption for humans, this article reviews the content and profile of phenolics in sorghum. It covers aspects of their health benefits and explores their mechanisms of action. The impact of thermal processing, such as boiling, steaming, roasting, and extrusion on sorghum phenolics is also discussed. Compelling data suggest the biological functions of sorghum phenolics, however, further investigations appear warrant to clarify the gap in the current research, and identify promising research topics in future.
CXCR3 Expression and Genome-Wide 3′ Splice Site Selection in the TCGA Breast Cancer Cohort

CXCR3 is a chemokine receptor with two well-characterized isoforms that have unique, context-dependent roles: CXCR3-A and CXCR3-B, which are produced through alternative 3′ splice site selection (A3SS). RNA-seq data from The Cancer Genome Atlas (TCGA) were used to correlate CXCR3 expression with breast cancer progression. This analysis revealed significant CXCR3 expression patterns associated with survival and differential expression between the tumor and adjacent normal tissue. TCGA data were used to estimate abundance of immune cells in breast cancer, which demonstrated the association of CXCR3 with immune infiltration, particularly in the triple-negative subtype. Given the importance of A3SS in CXCR3, genome-wide analysis of A3SS events was performed to identify events that were differentially spliced between breast cancer tissue and adjacent normal tissue. A total of 481 splicing events in 424 genes were found to be differentially spliced. The parent genes of differentially spliced events were enriched in RNA processing and splicing functions, indicating an underappreciated role of A3SS in the integrated splicing network of breast cancer. These results further validated the role of CXCR3 in immune infiltration of tumors, while raising questions about the role of A3SS splicing.
Severe Hepatic Insulin Resistance Induces Vascular Dysfunction: Improvement by Liver-Specific Insulin Receptor Isoform A Gene Therapy in a Murine Diabetic Model

Background: Cardiovascular dysfunction is linked to insulin-resistant states. In this paper, we analyzed whether the severe hepatic insulin resistance of an inducible liver-specific insulin receptor knockout (iLIRKO) might generate vascular insulin resistance and dysfunction, and whether insulin receptor (IR) isoforms gene therapy might revert it. Methods: We studied in vivo insulin signaling in aorta artery and heart from iLIRKO. Vascular reactivity and the mRNA levels of genes involved in vascular dysfunction were analyzed in thoracic aorta rings by qRT-PCR. Finally, iLIRKO mice were treated with hepatic-specific gene therapy to analyze vascular dysfunction improvement. Results: Our results suggest that severe hepatic insulin resistance was expanded to cardiovascular tissues. This vascular insulin resistance observed in aorta artery from iLIRKO mice correlated with a reduction in both PI3K/AKT/eNOS and p42/44 MAPK pathways, and it might be implicated in their vascular alterations characterized by endothelial dysfunction, hypercontractility and eNOS/iNOS levels’ imbalance. Finally, regarding long-term hepatic expression of IR isoforms, IRA was more efficient than IRB in the improvement of vascular dysfunction observed in iLIRKO mice. Conclusion: Severe hepatic insulin resistance is sufficient to produce cardiovascular insulin resistance and dysfunction. Long-term hepatic expression of IRA restored the vascular damage observed in iLIRKO mice.
Detecting Undifferentiation of Tertiary and County Hospitals in China in Adoption of DRG Instrument

(1) Background: Undifferentiated function for medical institutes in different levels had been a barrier to China’s healthcare reform. Thus, this study aimed to detect medical services that were capable offered both in tertiary and county hospitals in China and discuss the process of detection. (2) Method: Data of 2 tertiary hospitals that were city level and 12 county-level hospitals from one city in China were collected and grouped into diagnosis-related groups (DRGs). A strategy with four steps was devised by considering the aspects of service volume, in-hospital mortality rate, in-hospital adverse events rate, and inpatient cost. Additionally, a comparison of each indicator was made between city- versus county-level hospitals. (3) Results: There were no differences in service quality between the two levels of hospitals while county hospitals had lower average inpatient costs in 129 DRGs that covered 39.5% of all cases. About CNY 0.26 billion would be saved if certain cases were paid at county-level prices. (4) Conclusion: The study proposed a strategy with four steps that could help in locating the range of diseases in which patients’ admission suffered from the problem of undifferentiation between hospitals’ functions to reduce the irrational growth of healthcare expenditure.
The Roadmap of RANKL/RANK Pathway in Cancer

The receptor activator of the nuclear factor-κB ligand (RANKL)/RANK signaling pathway was identified in the late 1990s and is the key mediator of bone remodeling. Targeting RANKL with the antibody denosumab is part of the standard of care for bone loss diseases, including bone metastases (BM). Over the last decade, evidence has implicated RANKL/RANK pathway in hormone and HER2-driven breast carcinogenesis and in the acquisition of molecular and phenotypic traits associated with breast cancer (BCa) aggressiveness and poor prognosis. This marked a new era in the research of the therapeutic use of RANKL inhibition in BCa. RANKL/RANK pathway is also an important immune mediator, with anti-RANKL therapy recently linked to improved response to immunotherapy in melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). This review summarizes and discusses the pre-clinical and clinical evidence of the relevance of the RANKL/RANK pathway in cancer biology and therapeutics, focusing on bone metastatic disease, BCa onset and progression, and immune modulation.
Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Three Subjects with the Cystic Fibrosis Genotype Phe508del/Unknown and Advanced Lung Disease

We evaluated the effectiveness and safety of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in three subjects carrying the Phe508del/unknown CFTR genotype. An ex vivo analysis on nasal epithelial cells (NEC) indicated a significant improvement of CFTR gating activity after the treatment. Three patients were enrolled in an ELX/TEZ/IVA managed-access program, including subjects with the highest percent predicted Forced Expiratory Volume in the 1st second (ppFEV1) < 40 in the preceding 3 months. Data were collected at baseline and after 8, 12 and 24 weeks of follow-up during treatment. All patients showed a considerable decrease of sweat chloride (i.e., meanly about 60 mmol/L as compared to baseline), relevant improvement of ppFEV1 (i.e., >8) and six-minute walk test, and an increase in body mass index after the first 8 weeks of treatment. No pulmonary exacerbations occurred during the 24 weeks of treatment and all domains of the CF Questionnaire-Revised improved. No safety concerns related to the treatment occurred. This study demonstrates the benefit from the ELX/TEZ/IVA treatment in patients with CF with the Phe508del and one unidentified CFTR variant. The preliminary ex vivo analysis of the drug response on NEC helps to predict the in vivo therapeutic endpoints.
Variations in Patients’ Overall Assessment of Their Health Across and Within Disease Groups Using the EQ-5D Questionnaire: Protocol for a Longitudinal Study in the Swedish National Quality Registers

Background EQ-5D is one of the most commonly used questionnaires to measure health-related quality of life. It is included in many of the Swedish National Quality Registers (NQRs). EQ-5D health states are usually summarized using “values” obtained from members of the general public, a majority of whom are healthy. However, an alternative, which remains to be studied in detail, is the potential to use patients’ self-reported overall health on the visual analog scale (VAS) as a means of capturing experience-based perspective. Objective The aim of this study is to assess EQ VAS as a valuation method with an experience-based perspective through comparison of its performance across and within patient groups, and with that of the general population in Sweden. Methods Data on nearly 700,000 patients from 12 NQRs covering a variety of diseases/conditions and nearly 50,000 individuals from the general population will be analyzed. The EQ-5D-3L data from the 12 registers and EQ-5D-5L data from 2 registers will be used in the analyses. Longitudinal studies of patient-reported outcomes among different patient groups will be conducted in the period from baseline to 1-year follow-up. Descriptive statistics and analyses comparing EQ-5D dimensions and observed self-assessed EQ VAS values across and within patient groups will be performed. Comparisons of the change in health state and observed EQ VAS values at 1-year follow-up will also be undertaken. Regression models will be used to assess whether EQ-5D dimensions predict observed EQ VAS values to investigate patient value sets in each patient group. These will be compared across the patient groups and with the existing Swedish experience-based VAS and time trade-off value sets obtained from the general population. Results Data retrieval started in May 2019 and data of patients in the 12 NQRs and from the survey conducted among the general population have been retrieved. Data analysis is ongoing on the retrieved data. Conclusions This research project will provide information on the differences across and within patient groups in terms of self-reported health status through EQ VAS and comparison with the general population. The findings of the study will contribute to the literature by exploring the potential of self-assessed EQ VAS values to develop value sets using an experience-based perspective. Trial Registration ClinicalTrials.gov NCT04359628; https://clinicaltrials.gov/ct2/show/NCT04359628. International Registered Report Identifier (IRRID) DERR1-10.2196/27669