Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Hypoxia-Induced Mitogenic Factor in Organ-Specific Inflammation in the Lung and Liver: Key Concepts and Gaps in Knowledge Regarding Molecular Mechanisms of Acute or Immune-Mediated Liver Injury

Hypoxia-induced mitogenic factor (HIMF), which is also known as resistin-like molecule α (RELM-α), found in inflammatory zone 1 (FIZZ1), or resistin-like alpha (retlna), is a cysteine-rich secretory protein and cytokine. HIMF has been investigated in the lung as a mediator of pulmonary fibrosis, inflammation and as a marker for alternatively activated macrophages. Although these macrophages have been found to have a role in acute liver injury and acetaminophen toxicity, few studies have investigated the role of HIMF in acute or immune-mediated liver injury. The aim of this focused review is to analyze the literature and examine the effects of HIMF and its human homolog in organ-specific inflammation in the lung and liver. We followed the guidelines set by PRISMA in constructing this review. The relevant checklist items from PRISMA were included. Items related to meta-analysis were excluded because there were no randomized controlled clinical trials. We found that HIMF was increased in most models of acute liver injury and reduced damage from acetaminophen-induced liver injury. We also found strong evidence for HIMF as a marker for alternatively activated macrophages. Our overall risk of bias assessment of all studies included revealed that 80% of manuscripts demonstrated some concerns in the randomization process. We also demonstrated some concerns (54.1%) and high risk (45.9%) of bias in the selection of the reported results. The need for randomization and reduction of bias in the reported results was similarly detected in the studies that focused on HIMF and the liver. In conclusion, we propose that HIMF could be utilized as a marker for M2 macrophages in immune-mediated liver injury. However, we also detected the need for randomized clinical trials and additional experimental and human prospective studies in order to fully comprehend the role of HIMF in acute or immune-mediated liver injury.
Impact of Carbon Ion Radiotherapy on Inoperable Bone Sarcoma

Simple Summary The standard treatment for bone sarcoma is surgery with or without additional chemotherapy; however, complete resection of the tumor might not be possible in patients with locally advanced lesions. Management of patients with bone sarcoma who are unsuitable for surgery is challenging. Carbon ion radiotherapy (C-ion RT) was initiated in 1994 for treating various cancers in Japan and is being considered to be an effective treatment for unresectable bone sarcoma. However, there is a limited number of reports on the clinical outcomes of C-ion RT for bone sarcoma. Here, we aimed to analyze the clinical outcomes and prognostic factors among patients with unresectable bone sarcoma who were treated with C-ion RT. We found that C-ion RT had favorable overall survival and local control with low toxicity rates compared to surgery. Therefore, our results suggest a potential role for C-ion RT in the radical treatment of inoperable bone sarcoma. Abstract Management of patients with bone sarcoma who are unsuitable for surgery is challenging. We aimed to analyze the clinical outcomes among such patients who were treated with carbon ion radiotherapy (C-ion RT). We reviewed the medical records of the patients treated with C-ion RT between April 2011 and February 2019 and analyzed the data of 53 patients. Toxicities were classified using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (Version 4.0). The median follow-up duration for all patients was 36.9 months. Histologically, 32 patients had chordoma, 9 had chondrosarcoma, 8 had osteosarcoma, 3 had undifferentiated pleomorphic sarcoma, and 1 had sclerosing epithelioid fibrosarcoma. The estimated 3-year overall survival (OS), local control (LC), and progression-free survival (PFS) rates were 79.7%, 88.6%, and 68.9%, respectively. No patients developed grade 3 or higher acute toxicities. Three patients developed both grade 3 radiation dermatitis and osteomyelitis, one developed both grade 3 radiation dermatitis and soft tissue infection, and one developed rectum-sacrum-cutaneous fistula. C-ion RT showed favorable clinical outcomes in terms of OS, LC, and PFS and low rates of toxicity in bone sarcoma patients. These results suggest a potential role for C-ion RT in the management of this population.
Expression Profiles of Alkaloid-Related Genes across the Organs of Narrow-Leafed Lupin (Lupinus angustifolius L.) and in Response to Anthracnose Infection

The main restraint obstructing the wider adoption of lupins as protein crops is the presence of bitter and toxic quinolizidine alkaloids (QAs), whose contents might increase under exposure to stressful environmental conditions. A poor understanding of how QAs accumulate hinders the breeding of sweet varieties. Here, we characterize the expression profiles of QA-related genes, along with the alkaloid content, in various organs of sweet and bitter narrow-leafed lupin (NLL, Lupinus angustifolius L.). Special attention is paid to the RAP2-7 transcription factor, a candidate regulator of the QA pathway. We demonstrate the upregulation of RAP2-7 and other QA-related genes, across the aerial organs of a bitter cultivar and the significant correlations between their expression levels, thus supporting the role of RAP2-7 as an important regulatory gene in NLL. Moreover, we showed that the initial steps of QA synthesis might occur independently in all aerial plant organs sharing common regulatory mechanisms. Nonetheless, other regulatory steps might be involved in RAP2-7-triggered QA accumulation, given its expression pattern in leaves. Finally, the examination of QA-related gene expression in plants infected with Colletotrichum lupini evidenced no connection between QA synthesis and anthracnose resistance, in contrast to the important role of polyamines during plant–pathogen interactions.
Phosphodiesterases Expression during Murine Cardiac Development

3′-5′ cyclic nucleotide phosphodiesterases (PDEs) are a large family of enzymes playing a fundamental role in the control of intracellular levels of cAMP and cGMP. Emerging evidence suggested an important role of phosphodiesterases in heart formation, but little is known about the expression of phosphodiesterases during cardiac development. In the present study, the pattern of expression and enzymatic activity of phosphodiesterases was investigated at different stages of heart formation. C57BL/6 mice were mated and embryos were collected from 14.5 to 18.5 days of development. Data obtained by qRT-PCR and Western blot analysis showed that seven different isoforms are expressed during heart development, and PDE1C, PDE2A, PDE4D, PDE5A and PDE8A are modulated from E14.5 to E18.5. In heart homogenates, the total cAMP and cGMP hydrolytic activity is constant at the evaluated times, and PDE4 accounts for the majority of the cAMP hydrolyzing ability and PDE2A accounts for cGMP hydrolysis. This study showed that a subset of PDEs is expressed in developing mice heart and some of them are modulated to maintain constant nucleotide phosphodiesterase activity in embryonic and fetal heart.
The Role of Hip Joint Clearance Discrepancy as Other Clinical Predictor of Reinjury and Injury Severity in Hamstring Tears in Elite Athletes

Hamstring tear injuries (HTI) are the most prevalent injuries in athletes, with high reinjury rates. To prevent reinjury and reduce the severity of injuries, it is essential to identify potential risk factors. Hip characteristics are fundamental to optimal hamstring function. We sought to investigate the role of hip joint clearance discrepancy (JCD) as a risk factor for HTI and a clinical predictor of risk of reinjury and injury severity. A cross-sectional, retrospective study was performed with elite athletes (n = 100) who did (n = 50) and did not (n = 50) have a history of injury. X-rays were taken to assess JCD. We reviewed muscular lesions historial, and health records for the previous 5 years. Significant differences were found in injury severity (p = 0.026; ŋ2p = 0.105) and a number of injuries (p = 0.003; ŋ2p = 0.172). The multivariate analysis data indicated that JCD was significantly associated with the number of injuries and their severity (p < 0.05). In the stepwise regression model, JCD variability explained 60.1% of the number of injuries (R2 0.601) and 10.5% of injury severity (R2 0.0105). These results suggest that JCD could play an important role as a risk factor for HTI and also as a clinical predictor of reinjury and injury severity.
Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity

Simple Summary Pancreatic cancer, in its most common manifestation pancreatic ductal adenocarcinoma (PDAC), is a uniquely lethal disease with very limited treatment options and few prognostic biomarkers. Tumor budding is a proven independent, adverse prognostic factor in many tumor types including PDAC. Tumor buds can be detected histologically as single cancer cells or clusters of up to four cancer cells at the tumor invasive front. Tumor budding is biologically correlated to the induction of epithelial-mesenchymal transitions (EMT) and disease progression. In this study, we sought to investigate the immunological composition of tumors with high levels of tumor budding. We show that PDAC cases with a high grade of tumor budding display notably diminished anti-tumor immunity. These findings were further validated by gene expression analysis of PDAC cases from The Cancer Genome Atlas (TCGA). Our results provide insight on the immune escape mechanisms of tumor cells undergoing EMT. This offers the potential of designing novel treatments combining immunotherapies with EMT-targeted drugs. Abstract Tumor budding is associated with epithelial-mesenchymal transition and diminished survival in a number of cancer types including pancreatic ductal adenocarcinoma (PDAC). In this study, we dissect the immune landscapes of patients with high grade versus low grade tumor budding to determine the features associated with immune escape and disease progression in pancreatic cancer. We performed immunohistochemistry-based quantification of tumor-infiltrating leukocytes and tumor bud assessment in a cohort of n = 111 PDAC patients in a tissue microarray (TMA) format. Patients were divided based on the ITBCC categories of tumor budding as Low Grade (LG: categories 1 and 2) and High Grade (HG: category 3). Tumor budding numbers and tumor budding grade demonstrated a significant association with diminished overall survival (OS). HG cases exhibit notably reduced densities of stromal (S) and intratumoral (IT) T cells. HG cases also display lower M1 macrophages (S) and increased M2 macrophages (IT). These findings were validated using gene expression data from TCGA. A published tumor budding gene signature demonstrated a significant association with diminished survival in PDAC patients in TCGA. Immune-related gene expression revealed an immunosuppressive TME in PDAC cases with high expression of the budding signature. Our findings highlight a number of immune features that permit an improved understanding of disease progression and EMT in pancreatic cancer.
Genome‐wide profiling of miRNAs during seed development reveals their functional relevance in seed size/weight determination in chickpea

Abstract MicroRNAs (miRNAs) are non‐coding small RNAs that regulate gene expression at transcriptional and post‐transcriptional levels. The role of miRNAs in seed development and seed size/weight determination is poorly understood in legumes. In this study, we profiled miRNAs at seven successive stages of seed development in a small‐seeded and a large‐seeded chickpea cultivar via small RNA sequencing. In total, 113 known and 243 novel miRNAs were identified. Gene ontology analysis revealed the enrichment of seed/reproductive/post‐embryonic development and signaling pathways processes among the miRNA target genes. A large fraction of the target genes exhibited antagonistic correlation with miRNA expression. The sets of co‐expressed miRNAs showing differential expression between the two cultivars were recognized. Known transcription factor (TF) encoding genes involved in seed size/weight determination, including SPL, GRF, MYB, ARF, HAIKU1, SHB1, KLUH/CYP78A5, and E2Fb along with novel genes were found to be targeted by the predicted miRNAs. Differential expression analysis revealed higher transcript levels of members of SPL and REVOLUTA TF families and lower expression of their corresponding miRNAs in the large‐seeded cultivar. At least 19 miRNAs known to be involved in seed development or differentially expressed between small‐seeded and large‐seeded cultivars at late‐embryogenesis and/or mid‐maturation stages were located within known quantitative trait loci (QTLs) associated with seed size/weight determination. Moreover, 41 target genes of these miRNAs were also located within these QTLs. Altogether, we revealed important roles of miRNAs in seed development and identified candidate miRNAs and their target genes that have functional relevance in determining seed size/weight in chickpea.
Epidemiology and Clinical Characteristics of Non-Hodgkin Lymphoma in Mexico

Background There is no epidemiological registry in Mexico. The information about the epidemiology in our country is obtained by these types of studies, such as multicentric studies. A lot of improvements in the survival in non-Hodgkin lymphoma patients had occurred in the last 20 years. The access to treatment in these types of pathology could change the prognostic factors in Mexican Mestizos patients. The primary objective of the study was to learn what the most frequent histological varieties of non-Hodgkin lymphoma in Mexico are. The secondary objectives included clinical characteristics, treatments used, treatment response, disease-free survival and overall survival. Methods A retrospective, descriptive study of consecutive cases was carried out in 14 hospitals across 14 Mexican states with patients diagnosed with non-Hodgkin lymphoma using the World Health Organization (WHO) 2008 criteria. Inclusion criteria included: ≥ 18 years of age, male or female, any clinical stage at diagnosis, who had received any chemotherapy regimen, with a known outcome. Descriptive statistics was performed for all variables, and survival was assessed using Kaplan-Meier curves. Results Totally, 609 patients were enrolled, of which 545 were B-cell lymphomas and 64 were T-cell lymphomas. Median ages were 61 and 50, respectively. B-cell lymphomas were more common in males with 52.1%, and 65.5% of T-cell lymphomas occurred in females. For B-cell lymphomas, the two most frequent histological subtypes were diffuse large B-cell lymphoma in 63.9%, followed by follicular lymphoma at 18%. Meanwhile, 50% of T-cell lymphomas were of the T/natural killer (NK) subtype, and 87.1% of the patients received a CHOP-like regimen. Radiotherapy was given to 31% of B-cell Lymphomas and 46.9% of T-cell lymphomas. Overall survival at 9 years was 84.6% for B-cell lymphomas, and 73.4% for T-cell lymphomas. Conclusions Diffuse large B-cell lymphoma constitutes the most frequent subtype for B-cell lymphomas in Mexico. The most frequent T-cell lymphoma is the NK/T histological subtype.
Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice

Although physical exercise-induced autophagy activation has been considered a therapeutic target to enhance tissue health and extend lifespan, the effects of different exercise models on autophagy in specific metabolic tissues are not completely understood. This descriptive investigation compared the acute effects of endurance (END), exhaustive (ET), strength (ST), and concurrent (CC) physical exercise protocols on markers of autophagy, genes, and proteins in the gastrocnemius muscle, heart, and liver of mice. The animals were euthanized immediately (0 h) and six hours (6 h) after the acute exercise for the measurement of glycogen levels, mRNA expression of Prkaa1, Ppargc1a, Mtor, Ulk1, Becn1, Atg5, Map1lc3b, Sqstm1, and protein levels of Beclin 1 and ATG5. The markers of autophagy were measured by quantifying the protein levels of LC3II and Sqstm1/p62 in response to three consecutive days of intraperitoneal injections of colchicine. In summary, for gastrocnemius muscle samples, the main alterations in mRNA expressions were observed after 6 h and for the ST group, and the markers of autophagy for the CC group were increased (i.e., LC3II and Sqstm1/p62). In the heart, the Beclin 1 and ATG5 levels were downregulated for the ET group. Regarding the markers of autophagy, the Sqstm1/p62 in the heart tissue was upregulated for the END and ST groups, highlighting the beneficial effects of these exercise models. The liver protein levels of ATG5 were downregulated for the ET group. After the colchicine treatment, the liver protein levels of Sqstm1/p62 were decreased for the END and ET groups compared to the CT, ST, and CC groups. These results could be related to diabetes and obesity development or liver dysfunction improvement, demanding further investigations.
The Effect of Surface Treatment on Structural Properties of CVD Diamond Layers with Different Grain Sizes Studied by Raman Spectroscopy

Extensive Raman spectroscopy studies combined with scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) measurements were performed to investigate structural and chemical changes in diamond layers deposited by chemical vapour deposition (CVD) upon post-growth treatment with hydrogen. The aim of this study is to characterize the changes in micro-structural properties of diamond layers with different grain sizes and different contents of sp2 carbon phase. Hydrogenation or oxidization of diamond layer surface is often performed to modify its properties; however, it can also strongly affect the surface structure. In this study, the impact of hydrogenation on the structure of diamond layer surface and its chemical composition is investigated. Owing to their polycrystalline nature, the structural properties of CVD diamond layers can strongly differ within the same layer. Therefore, in this project, in order to compare the results before and after hydrogen treatment, the diamond layers are subjected to Raman spectroscopy studies in the vicinity of a T-shape marker fabricated on the surface of each diamond layer studied.
New Polyporphyrin Arrays with Controlled Fluorescence Obtained by Diaxial Sn(IV)-Porphyrin Phenolates Chelation with Cu2+ Cation

New coordination oligomers and polymers of Sn(IV)-tetra(4-sulfonatophenyl)porphyrin have been constructed by the chelation reaction of its diaxialphenolates with Cu2+. The structure and properties of the synthesized polyporphyrin arrays were investigated by 1H Nuclear Magnetic Resonance (1H NMR), Infra Red (IR), Ultra Violet - Visible (UV-Vis) and fluorescence spectroscopy, mass spectrometry, Powder X-Rays Diffraction (PXRD), Electron Paramagnetic Resonance (EPR), thermal gravimetric, elemental analysis, and quantum chemical calculations. The results show that the diaxial coordination of bidentate organic ligands (L-tyrazine and diaminohydroquinone) leads to the quenching of the tetrapyrrole chromophore fluorescence, while the chelation of the porphyrinate diaxial complexes with Cu2+ is accompanied by an increase in the fluorescence in the organo-inorganic hybrid polymers formed. The obtained results are of particular interest to those involved in creating new ‘chemo-responsive’ (i.e., selectively interacting with other chemical species as receptors, sensors, or photocatalysts) materials, the optoelectronic properties of which can be controlled by varying the number and connection type of monomeric fragments in the polyporphyrin arrays.
THE PERFORMANCE OF LAYING HENS FED DIFFERENT CALCIUM SOURCE

The research was aimed to evaluate the performance of laying hens fed different calcium sources.Two hundreds of Isa Brown laying hens were used in this study. The hens were raised in individualbattery cages units for 12 weeks. Four calcium source (limestone as a control, 5% limestone + 2.5%eggshells waste, 2.5% limestone + 5% eggshells waste and 7.5% eggshell waste) were used in feedexperiment. A completely randomized design was applied, with 4 treatments and 5 replications. Eachexperimental unit consisted of 10 laying hens. The parameters measured were feed intake, proteinintake, calcium intake, phosphorus intake, egg production, egg weight and feed conversion ratio. Resultsof the research showed that the calcium source had significantly effect on performance productions. Theuse of eggshell waste 7.5% significantly increased the feed intake, calcium intake, phosphorus intake,egg production and egg weight except for feed conversion ratio. The conclusion of this research was thatthe use of eggshell waste as calcium source of feed resulted in better performance than using limestoneor mixed limestone with eggshell waste.
Gender-Specific Effects of Two Treatment Strategies in a Mouse Model of Niemann-Pick Disease Type C1

In a mouse model of Niemann-Pick disease type C1 (NPC1), a combination therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPßCD) has previously resulted in, among other things, significantly improved motor function. The present study was designed to compare the therapeutic effects of the COMBI therapy with that of MIGLU or HPßCD alone on body and brain weight and the behavior of NPC1−/− mice in a larger cohort, with special reference to gender differences. A total of 117 NPC1−/− and 123 NPC1+/+ mice underwent either COMBI, MIGLU only, HPßCD only, or vehicle treatment (Sham), or received no treatment at all (None). In male and female NPC1−/− mice, all treatments led to decreased loss of body weight and, partly, brain weight. Concerning motor coordination, as revealed by the accelerod test, male NPC1−/− mice benefited from COMBI treatment, whereas female mice benefited from COMBI, MIGLU, and HPßCD treatment. As seen in the open field test, the reduced locomotor activity of male and female NPC1−/− mice was not significantly ameliorated in either treatment group. Our results suggest that in NPC1−/− mice, each drug treatment scheme had a beneficial effect on at least some of the parameters evaluated compared with Sham-treated mice. Only in COMBI-treated male and female NPC+/+ mice were drug effects seen in reduced body and brain weights. Upon COMBI treatment, the increased dosage of drugs necessary for anesthesia in Sham-treated male and female NPC1−/− mice was almost completely reduced only in the female groups.