Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of MAPK and PI3K/AKT/mTOR Proteins according to the Chronic Liver Disease Etiology in Hepatocellular Carcinoma

Aims Chronic liver disease (CLD) of different etiologies leads to hepatocellular carcinoma (HCC) by multiple mechanisms that may be translated into clinicopathological differences. We evaluated the tissue expression of the MAPK and PI3K/Akt/mTOR pathway proteins and their association with long-term outcome and other parameters, according to the etiology of the CLD, in HCC patients. Methods Clinicopathological data from 80 patients who underwent orthotopic liver transplantation for HCC treatment in a Brazilian referral center were compared according to CLD etiology. Event (tumor recurrence or death from any cause) occurrence and event-free survival (EFS) were analyzed. Pathway protein expression was assessed by immunohistochemistry (IHQ) in both tumor and underlying cirrhosis and by RT-PCR in tumor tissue. Results Strong expression (SE) of KRAS was more frequent in tumors arising from viral (26.8%) than the nonviral group of liver disease (7.7%, p=0.024) and also than cirrhotic parenchyma (0%, p=0.004). SE of PI3K was more frequent in tumor than in cirrhosis (p=0.048, p < 0.01), without differences in its tumor expression among etiologic groups (p=0.111). mRNA of ERK, PI3K, and BRAF was expressed in the tumor, without differences between CLD etiologies, and there was no association with IHQ findings. Older age and microvascular invasion (MIV) were the only parameters independently associated with the event. MIV was also associated with shorter EFS. Conclusions Hepatitis B and C virus can lead to HCC by different mechanisms compared with nonviral hepatopathy. KRAS and PI3K may have a role in carcinogenesis. The prognostic and therapeutic implications need to be investigated.
Plant Growth-Promoting Rhizobacteria Isolated from Degraded Habitat Enhance Drought Tolerance of Acacia (Acacia abyssinica Hochst. ex Benth.) Seedlings

Drought stress (DS) is the most impacting global phenomenon affecting the ecological balance of a particular habitat. The search for potential plant growth-promoting rhizobacteria (PGPR) capable of enhancing plant tolerance to drought stress is needed. Thus, this study was initiated to evaluate the effect of inoculating Acacia abyssinica seedlings with PGPR isolated from rhizosphere soil of Ethiopia to enhance DS tolerance. The strains were selected based on in vitro assays associated with tolerance to drought and other beneficial traits such as salinity, acidity, temperature, heavy metal tolerances, biofilm formation, and exopolysaccharide (EPS) production. The strains with the best DS tolerance ability were selected for the greenhouse trials with acacia plants. The results indicate that out of 73 strains, 10 (14%) were completely tolerant to 40% polyethylene glycol. Moreover, 37% of the strains were strong biofilm producers, while 66 (90.41%) were EPS producers with a better production in the medium containing sucrose at 28 ± 2°C and pH 7 ± 0.2. Strains PS-16 and RS-79 showed tolerance to 11% NaCl. All the strains were able to grow in wider ranges of pH (4–10) and temperature (15–45°C) and had high tolerance to heavy metals. The inoculated bacterial strains significantly (p ≤ 0.05) increased root and shoot length and dry biomass of acacia plants. One of the strains identified as P. fluorescens strain FB-49 was outstanding in enhancing DS tolerance compared to the single inoculants and comparable to consortia. Stress-tolerant PGPR could be used to enhance acacia DS tolerance after testing other phytobeneficial traits.
The Pivotal Potentials of Scorpion Buthus Martensii Karsch-Analgesic-Antitumor Peptide in Pain Management and Cancer

Scorpion Buthus martensii Karsch -analgesic-antitumor peptide (BmK AGAP) has been used to treat diseases like tetanus, tuberculosis, apoplexy, epilepsy, spasm, migraine headaches, rheumatic pain, and cancer in China. AGAP is a distinctive long-chain scorpion toxin with a molecular mass of 7142 Da and composed of 66 amino acids cross-linked by four disulfide bridges. Voltage-gated sodium channels (VGSCs) are present in excitable membranes and partakes in essential roles in action potentials generation as compared to the significant function of voltage-gated calcium channels (VGCCs). A total of nine genes (Nav1.1–Nav1.9) have been recognized to encode practical sodium channel isoforms. Nav1.3, Nav1.7, Nav1.8, and Nav1.9 have been recognized as potential targets for analgesics. Nav1.8 and Nav1.9 are associated with nociception initiated by inflammation signals in the neuronal pain pathway, while Nav1.8 is fundamental for neuropathic pain at low temperatures. AGAP has a sturdy inhibitory influence on both viscera and soma pain. AGAP potentiates the effects of MAPK inhibitors on neuropathic as well as inflammation-associated pain. AGAP downregulates the secretion of phosphorylated p38, phosphorylated JNK, and phosphorylated ERK 1/2 in vitro. AGAP has an analgesic activity which may be an effective therapeutic agent for pain management because of its downregulation of PTX3 via NF-κB and Wnt/beta-catenin signaling pathway. In cancers like colon cancer, breast cancer, lymphoma, and glioma, rAGAP was capable of blocking the proliferation. Thus, AGAP is a promising therapy for these tumors. Nevertheless, research is needed with other tumors.
Prevalence of Depression and the Quality-of-Life of Breast Cancer Patients in Jordan

Objective The objectives of the current study are to evaluate the prevalence of depression symptoms among breast cancer patients in Jordan and impact of the disease on patient’s quality-of-life. Methods A cross-sectional survey-based study was conducted over a 6-month period among breast cancer patients attending two major hospitals in Jordan. A validated questionnaire was used to evaluate the prevalence of depression symptoms and quality-of-life aspects among those patients utilizing Beck’s Depression Inventory-II score and 36-Item Survey Form (SF-36) score, respectively. Results The mean age±SD of patients (n=169) was 49.12±6.48 years. Depression symptoms were reported in 30.2% of patients. As for quality-of-life, the physical functioning (PF) subscale was significantly associated with the patient’s age (P=0.03). The role-physical (RP) subscale was associated with number of sleeping hours (P=0.038). Marital status of breast cancer patients was significantly associated with role-emotional (RE) (P=0.015) and mental health (MH) (P=0.009) subscales. The number of patient’s siblings was significantly associated with daily habits such as PF (P=0.031) and RP (P=0.005) subscales. Moreover, the occupation of patients was associated with the PF (P=0.041) and MH (P=0.049). Conclusion About one-third of breast cancer patients reported depression symptoms. Quality-of-life subscales among those patients were associated with multiple social and health determinants, such as age, marital status, number of siblings, occupation, and number of sleeping hours. There is urgent need to support this group of patients to help them to cope with depression symptoms and to improve their quality-of-life.
NARFIB: A Novel Prognostic Score Based on the Neutrophil-to-Albumin Ratio and Fibrinogen Can Predict the Prognosis of Gastrointestinal Stromal Tumors

Objective The neutrophil-to-albumin ratio (NAR) and fibrinogen are significantly related to tumor progression. The present study evaluated the prognostic impact of the NAR plus fibrinogen concentration in gastrointestinal stromal tumor (GIST) cases. Methods The baseline characteristics, postoperative NAR, and fibrinogen concentrations were retrospectively analyzed for 229 Chinese patients who underwent radical gastrectomy for GIST. Receiver operating characteristic (ROC) curves were applied to estimate the optimal critical points for NAR and fibrinogen. Cox regression analysis was applied to determine significant prognostic variables. Results Multivariate analyses revealed that poor recurrence-free survival was associated with elevated values for fibrinogen (hazard ratio [HR]: 5.015, 95% confidence interval [CI]: 1.993–12.619, P=0.001) and NAR (HR: 4.669, 95% CI: 1.776–12.273, P = 0.002). Combining fibrinogen and the NAR into the NARFIB score provided an area under the ROC curve of 0.833, which was greater than the areas for NAR (0.708) or fibrinogen (0.778). When the NAR and fibrinogen were replaced by the NARFIB score in the multivariate analysis, the independent prognosticators were tumor site (HR: 2.927, 95% CI: 1.417–6.045, P=0.004), mitotic index (HR: 2.661, 95% CI: 1.110–6.380, P=0.028), and the NARFIB score (HR: 14.116, 95% CI: 3.243–61.443, P<0.001). The NARFIB score retained its prognostic significance in various subgroup analyses and was significantly related to gender, surgical approach, tumor size, mitosis, tumor site, risk classification, and recurrence. Conclusion These results suggest that the NARFIB score may help guide prognostication and risk stratification for GIST, which might benefit from targeted therapy.
Effects of sire line, birth weight and sex on growth performance and carcass traits of crossbred pigs under standardized environmental conditions

Abstract A variety of available terminal sire lines makes the choice of terminal sire line complex for the pig producer. Higher birth weights are important for subsequent growth performance and selection for this trait is also necessary in sire lines. The aim was to investigate the effect of sire line, birth weight and gender on growth performance, carcass traits and meat quality. In total 3844 crossbred pigs from Camborough Pig Improvement Company (PIC) dams matched with either a Synthetic (A) or Piétrain (B) sire line were used. Pigs from line A grew faster (p<0.01), showed higher feed intake (p<0.01) and reached a higher final body weight (p≤0.01), but they had a similar efficiency (p=0.179). Leaner carcasses and heavier primal cuts (p<0.001) were observed in pigs from line B. Carcasses from pigs sired by line A had higher meat quality (p<0.001). Males had a higher growth rate (p≤0.05) but had a poorer feed efficiency (p<0.01). Heavier birth weight pigs and females had leaner, higher value carcasses with heavier primal cuts (p<0.001) compared to middle and low birth weight females or males. Sire line by sex interactions was significant for growth (p≤0.05) and carcass traits (p<0.001). Interaction between sire line and birth weight classes were only detected for loin depth (p<0.01). Line A is preferable if the numbers of fatting pigs per fattening place and year should be improved, and line B is an option to increase leanness and carcass primal cuts.
Magnesium hydroxide-incorporated PLGA composite attenuates inflammation and promotes BMP2-induced bone formation in spinal fusion

Spinal fusion has become a common surgical technique to join two or more vertebrae to stabilize a damaged spine; however, the rate of pseudarthrosis (failure of fusion) is still high. To minimize pseudarthrosis, bone morphogenetic protein-2 (BMP2) has been approved for use in humans. In this study, we developed a poly(lactide-co-glycolide) (PLGA) composite incorporated with magnesium hydroxide (MH) nanoparticles for the delivery of BMP2. This study aimed to evaluate the effects of released BMP2 from BMP2-immobilized PLGA/MH composite scaffold in an in vitro test and an in vivo mice spinal fusion model. The PLGA/MH composite films were fabricated via solvent casting technique. The surface of the PLGA/MH composite scaffold was modified with polydopamine (PDA) to effectively immobilize BMP2 on the PLGA/MH composite scaffold. Analyzes of the scaffold revealed that using PLGA/MH-PDA improved hydrophilicity, degradation performance, neutralization effects, and increased BMP2 loading efficiency. In addition, releasing BMP2 from the PLGA/MH scaffold significantly promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells. Furthermore, the pH neutralization effect significantly increased in MC3T3-E1 cells cultured on the BMP2-immobilized PLGA/MH scaffold. In our animal study, the PLGA/MH scaffold as a BMP2 carrier attenuates inflammatory responses and promotes BMP2-induced bone formation in posterolateral spinal fusion model. These results collectively demonstrate that the BMP2-immobilized PLGA/MH scaffold offers great potential in effectively inducing bone formation in spinal fusion surgery.
Amorphized length and variability in phase-change memory line cells

The dimensions of amorphized regions in phase-change memory cells are critical parameters to design devices for different applications. However, these dimensions are difficult to be determined by direct imaging. In this work, the length of amorphized regions in multiple identical Ge2Sb2Te5 (GST) line cells was extracted from electrical measurements. After each cell was programmed to an amorphous state, a sequence of increasing-amplitude post-reset voltage pulses separated by low-amplitude read DC sweeps was applied. When a post-reset voltage pulse with sufficient amplitude was applied to a given cell, the measured current and the post-pulse resistance increased drastically, indicating that the cell re-amorphized after threshold switching, melting, and quenching. The amorphized length was calculated using the measured voltage at which the threshold switching occurred and the expected drifted threshold field at that time. The measured threshold voltage values and, hence, the extracted amorphized length, generally increase linearly with the programmed resistance levels. However, significant variability arises from the intrinsically unique crystallization and amorphization processes in these devices. For example, cells programmed to an amorphous resistance of approx. 50 MΩ show threshold voltage values of 5.5–7.5 V, corresponding to amorphized length values of 290–395 nm. This unpredictable programming feature in phase-change memory devices can be utilized in hardware security applications.
Efficacy and Mechanism of a Chinese Classic Prescription of Yueju in Treating Nonalcoholic Steatohepatitis and Protecting Hepatocytes from Apoptosis

Yueju, a famous classic Chinese prescription, has been extensively used in treating depression syndromes for hundreds of years. Recent studies have reported that Yueju showed good effects in treating metabolic diseases, such as obesity and hyperlipidemia. Nonalcoholic steatohepatitis (NASH), which leads to cirrhosis and severe cardiovascular diseases, is closely linked to obesity and abnormal lipid metabolism. In this study, Yueju could decrease the levels of alanine aminotransferase, aspartate transaminase, triglyceride, cholesterol, and low-density lipoprotein-C but increase the high-density lipoprotein-C in the serum of the NASH rat model induced by high-fat and high-cholesterol diet. Yueju could alleviate hepatosteatosis by increasing the phosphorylation of acetyl-CoA carboxylase and inhibiting the expression of fatty acid synthase and stearoyl-CoA desaturase 1. Yueju downregulated the expression of α-smooth muscle actin and collagen type 1A1, ameliorating the liver fibrilization. Yueju could also protect the hepatocytes from apoptosis by upregulating antiapoptosis protein Bcl-2 and X-linked inhibitor of apoptosis protein and downregulating apoptotic proteins Bax and cleaved poly ADP-ribose polymerase. Thus, Yueju could improve liver function, regulate lipid metabolism, alleviate hepatosteatosis and fibrosis, and protect hepatocytes from apoptosis against NASH. Yueju may be used as an alternative effective medicine for NASH treatment.
Expression profiles of the Wnt/β-catenin signaling-related extracellular antagonists during proliferation and differentiation in human osteoblast-like cells

Bone formation is a dynamic process directed by osteoblast activity. The transition from the proliferation to differentiation stage during osteoblast maturation involves the downregulation of the Wnt/β-catenin signaling pathway, and extracellular antagonists are important for the regulation of Wnt signaling. However, the expression levels of Wnt antagonists in these stages of human osteoblast maturation have not been fully elucidated. Therefore, the aim of the present study was to investigate the expression levels of extracellular Wnt antagonists during proliferation and differentiation in osteoblast-like cell lines. The results demonstrated an overlap between the differential expression of secreted Frizzled-related protein (SFPR)2, SFRP3, SFRP4 and Dickkopf (DKK) 2 genes during the differentiation stage in the MG-63 and Saos-2 cells. Furthermore, high expression levels of DKK3 in MG-63 cells, Wnt inhibitory factor 1 (WIF1) in Saos-2 cells and DKK4 in hFOB 1.19 cells during the same stage (differentiation), were observed. The upregulated expression levels of Wnt antagonists were also correlated with the high expression of anxin 2 during the differentiation stage. These findings suggested that Wnt-related antagonists could modulate the Wnt/β-catenin signaling pathway. By contrast, DKK1 was the only gene that was found to be upregulated during the proliferation stage in hFOB 1.19 and Saos-2 cells. To the best of our knowledge, the present study provides, for the first time, the expression profile of Wnt antagonists during the proliferation stage and the initial phases of differentiation in osteoblast-like cell lines. The current results offer a basis to investigate potential targets for bone-related Wnt-signaling modulation in bone metabolism research.
Breast Cancer in the United States: A Cross-Sectional Overview

Introduction Breast cancer remains the most commonly diagnosed malignancy in women. It encompasses considerable heterogeneity in pathology, patient clinical characteristics, and outcome. This study describes factors associated with overall survival (OS) of breast cancer in an updated national database. Methods We conducted a retrospective analysis of patients with breast cancer diagnosed between 2004 and 2016 based on the National Cancer Database. Categorical variables were summarized using frequencies/percentages, whereas continuous variables were summarized using the median/interquartile range (IQR). OS was explored using the Kaplan-Meier method. Results Data from n = 2,671,549 patients were analyzed. The median age at diagnosis was 61 years (range 18-90). 75% were non-Hispanic (NH) White; 11% were NH-Black; 4.7% were Hispanic-White; 0.1% were Hispanic-Black; and 3.4% were Asian. Most cases (73%) presented with ductal carcinoma histology; while 15% with lobular carcinoma. Rarer subtypes included epithelial-myoepithelial, fibroepithelial, metaplastic, and mesenchymal tumors. OS was associated with molecular subtype, histologic subtype, and AJCC clinical staging. Survival also correlated with race: a cohort including Asians and Pacific Islanders had the best survival, while Black patients had the worst. Finally, facility type also impacted outcome: patients at academic centers had the best survival, while those at community cancer programs had the worst. Conclusion This large database provides a recent and comprehensive overview of breast cancer over 12 years. Molecular subtype, histologic subtype, stage, race, and facility type were correlated with OS. In addition to the educational perspective of this overview, significant factors impacting the outcome identified here should be considered in future cancer research on disparities.
Progressive and Prognostic Performance of an Extracellular Matrix-Receptor Interaction Signature in Gastric Cancer

The role of an extracellular matrix- (ECM-) receptor interaction signature has not been fully clarified in gastric cancer. This study performed comprehensive analyses on the differentially expressed ECM-related genes, clinicopathologic features, and prognostic application in gastric cancer. The differentially expressed genes between tumorous and matched normal tissues in The Cancer Genome Atlas (TCGA) and validation cohorts were identified by a paired t-test. Consensus clusters were built to find the correlation between clinicopathologic features and subclusters. Then, the least absolute shrinkage and selection operator (lasso) method was used to construct a risk score model. Correlation analyses were made to reveal the relation between risk score-stratified subgroups and clinicopathologic features or significant signatures. In TCGA (26 pairs) and validation cohort (134 pairs), 25 ECM-related genes were significantly highly expressed and 11 genes were downexpressed in gastric cancer. ECM-based subclusters were slightly related to clinicopathologic features. We constructed a risk score model = 0.081∗log2 (CD36) + 0.043∗log2 (COL5A2) + 0.001∗log2 (ITGB5) + 0.039∗log2 (SDC2) + 0.135∗log2 (SV2B) + 0.012∗log2 (THBS1) + 0.068∗log2 (VTN) + 0.023∗log2 (VWF). The risk score model could well predict the outcome of patients with gastric cancer in both training (n = 351, HR: 1.807, 95% CI: 1.292-2.528, P = 0.00046) and validation (n = 300, HR: 1.866, 95% CI: 1.347-2.584, P = 0.00014) cohorts. Besides, risk score-based subgroups were associated with angiogenesis, cell adhesion molecules, complement and coagulation cascades, TGF-beta signaling, and mismatch repair-relevant signatures (P < 0.0001). By univariate (1.845, 95% CI: 1.382-2.462, P < 0.001) and multivariate (1.756, 95% CI: 1.284-2.402, P < 0.001) analyses, we regarded the risk score as an independent risk factor in gastric cancer. Our findings revealed that ECM compositions became accomplices in the tumorigenesis, progression, and poor survival of gastric cancer.
Inflammation, HIV, and Immune Quiescence: Leveraging on Immunomodulatory Products to Reduce HIV Susceptibility

The relationship between inflammation and HIV has been a focus of research over the last decade. In HIV-infected individuals, increased HIV-associated immune activation significantly correlated to disease progression. While genital inflammation (GI) has been shown to significantly increase the risk of HIV acquisition and transmission, immune correlates for reduced risk remain limited. In certain HIV-exposed seronegative individuals, an immune quiescent phenotype characterized reduced risk. Immune quiescence is defined by specific, targeted, highly regulated immune responses that hinder overt inflammation or immune activation. Targeted management of inflammation, therefore, is a plausible strategy to mitigate HIV risk and slow disease progression. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as hydroxychloroquine and aspirin have shown encouraging preliminary results in low-risk women by reducing systemic and genital immune activation. A topical NSAID, containing ibuprofen, is effective in treating vulvovaginal inflammation. Additionally, the glucocorticoids (GCs), prednisolone, and dexamethasone are used to treat HIV-associated immune activation. Collectively, these data inform on immune-modulating drugs to reduce HIV risk. However, the prolonged use of these pharmaceutical drugs is associated with adverse effects, both systemically and to a lesser extent topically. Natural products with their reduced side effects coupled with anti-inflammatory properties render them viable options. Lactic acid (LA) has immunomodulatory properties. LA regulates the genital microbiome by facilitating the growth of Lactobacillus species, while simultaneously limiting bacterial species that cause microbial dysbiosis and GI. Glycerol monolaurate, besides being anti-inflammatory, also inhibited SIV infections in rhesus macaques. The proposed pharmaceutical and natural products could be used in combination with either antiretrovirals for treatment or preexposure prophylaxis for HIV prevention. This review provides a summary on the associations between inflammation, HIV risk, and disease progression. Furthermore, we use the knowledge from immune quiescence to exploit the use of pharmaceutical and natural products as strategic interventions to manage inflammation, toward mitigating HIV infections.