Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel diversity in Lactifluus section Gerardii from Asia: five new species with pleurotoid or small agaricoid basidiocarps

ABSTRACT The ectomycorrhizal milkcap genus Lactifluus (Russulaceae) is commonly found in tropical and subtropical forests of Southeast Asia. During several sampling expeditions in Thailand, multiple collections of Lactifluus (Lf.) species with pleurotoid or small agaricoid basidiocarps were found. A molecular study was combined with a morphological study, in which the collections were compared with herbarium material. The molecular study indicated that four Thai collections belonged to undescribed species within Lactifluus section Gerardii, as was also the case for herbarium collections of a pleurotoid species from Nepal. One other collection from Thailand appeared closely related to Lf. uyedae, known only from Japan. Five species are described as new in the genus: Lf. auriculiformis, Lf. gerardiellus, Lf. bhandaryi, Lf. pulchrellus, and Lf. raspei.
Predicting Survival Using Pretreatment CT for Patients With Hepatocellular Carcinoma Treated With Transarterial Chemoembolization: Comparison of Models Using Radiomics.

OBJECTIVE The purpose of this study was to investigate the use of radiomics features as prognostic biomarkers for predicting the survival of patients treated with transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS We retrospectively analyzed 88 patients with HCC treated with TACE. High-dimensional quantitative feature analysis was applied to extract 116 radiomics features of pretreatment CT. A radiomics score model was constructed from these features with the use of least absolute shrinkage and selection operator Cox regression. A clinical score model was constructed from clinical variables with the use of multivariate Cox regression. A combined score model was constructed using the radiomics and clinical models. We compared the three models (the radiomics score, clinical score, and combined score models) for predicting overall survival, using Kaplan-Meier analysis and the log-rank test. RESULTS The following radiomics features were selected for the radiomics score model: histogram-based features (median, kurtosis, and energy), shape-based features (spherical disproportion and surface-to-volume ratio), gray-level co-occurrence matrix (GLCM)-based features (energy, informational measure of correlation, maximum probability, contrast, and sum average), and intensity size zone matrix-based features (size zone variability). For the clinical score model, the Child-Pugh score, α-fetoprotein level, and HCC size were included. The combined score model included five radiomics features (surface area-to-volume ratio, kurtosis, median, gray-level co-occurrence matrix contrast, and size zone variability) and three clinical factors (Child-Pugh score, α-fetoprotein level, and HCC size). The combined model was a better predictor of survival (hazard ratio, 19.88; p < 0.0001) than the clinical score model or the radiomics score model. CONCLUSION A radiomics approach combined with conventional clinical variables could be effective in predicting the survival of patients with HCC treated with TACE.
Predictive Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio in Head and Neck Squamous Cell Carcinoma

This study assessed the significance of the neutrophil-to-lymphocyte ratio (NLR) in head and neck squamous cell carcinoma (HNSCC), and the relationships of the NLR with the aldehyde dehydrogenase 1 (ALDH1) level in tumors and the proportion of myeloid-derived suppressor cells (MDSCs) in the peripheral circulation. In total, 227 HNSCC patients who had received curative treatment at our hospital were enrolled into the present study. The NLR of each HNSCC patient before treatment was calculated. The associations of NLR with various clinicopathological parameters and prognoses were then examined. In addition, correlations between the proportion of MDSCs and level of ALDH1 with the NLR were assessed. Our data revealed that an elevated NLR was significantly correlated with the risk of developing locoregional recurrence and with a reduced overall survival in HNSCC patients. Multivariate analyses revealed that the NLR pretreatment and surgical resection were significantly correlated with the rate of treatment failure and the overall survival rate in HNSCC patients. Furthermore, the levels of ALDH1 in tumors and MDSCs in the peripheral circulation were significantly correlated with the prognosis of HNSCC, and the NLR was positively correlated with MDSC levels in the circulation and ALDH1 staining intensity in tumor specimens. In conclusion, the NLR has power in predicting the expression of ALDH1 in tumors, the circulating level of MDSCs, and the prognosis in HNSCC. We suggest that the NLR is an important biomarker that can assist the clinician and patient in making informed decisions regarding treatment options for HNSCC patients.
Virus-Like Particles Are a Superior Platform for Presenting M2e Epitopes to Prime Humoral and Cellular Immunity against Influenza Virus

Influenza virus M2 protein has a highly conserved ectodomain (M2e) as a cross-protective antigenic target. We investigated the antigenic and immunogenic properties of tandem repeat M2e (5xM2e) proteins and virus-like particles (5xM2e VLP) to better understand how VLP and protein platform vaccines induce innate and protective adaptive immune responses. Despite the high antigenic properties of 5xM2e proteins, the 5xM2e VLP was superior to 5xM2e proteins in inducing IgG2a isotype antibodies, T cell responses, plasma cells and germinal center B cells as well as in conferring cross protection. Mice primed with 5xM2e VLP were found to be highly responsive to 5xM2e protein boost, overcoming the low immunogenicity and protective efficacy of 5xM2e proteins. Immunogenic differences between VLPs and proteins in priming immune responses might be due to an intrinsic ability of 5xM2e VLP to stimulate dendritic cells secreting T helper type 1 (Th1) cytokines. We also found that 5xM2e VLP was effective in inducing inflammatory cytokines and chemokines, and in recruiting macrophages, monocytes, neutrophils, and CD11b+ dendritic cells at the injection site. Therefore, this study provides evidence that 5xM2e VLP is an effective vaccine platform, inducing cross-protection by stimulating innate and adaptive immune responses.
Circulating Nucleic Acids Are Associated With Outcomes of Patients With Pancreatic Cancer.

BACKGROUND & AIMS We aimed to investigate the clinical utility of circulating tumor cell DNA (ctDNA) and exosome DNA (exoDNA) in pancreatic cancer. METHODS We collected liquid biopsy samples from 194 patients undergoing treatment for localized or metastatic pancreatic adenocarcinoma from April 7, 2015, through October 13, 2017 (425 blood samples collected before [baseline] and during therapy). Additional liquid biopsy samples were collected from 37 disease control individuals. Droplet digital polymerase chain reaction was used to determine KRAS mutant allele fraction (MAF) from ctDNA and exoDNA purified from plasma. For the longitudinal analysis, we analyzed exoDNA and ctDNA in 123 serial blood samples from 34 patients. We performed analysis including Cox regression, Fisher exact test, and Bayesian inference to associate KRAS MAFs in exoDNA and ctDNA with prognostic and predictive outcomes. RESULTS In the 34 patients with potentially resectable tumors, an increase in exoDNA level after neoadjuvant therapy was significantly associated with disease progression (P = .003), whereas ctDNA did not show correlations with outcomes. Concordance rates of KRAS mutations present in surgically resected tissue and detected in liquid biopsy samples were greater than 95%. On univariate analysis, patients with metastases and detectable ctDNA at baseline status had significantly shorter times of progression-free survival (PFS) (hazard ratio [HR] for death, 1.8; 95% CI, 1.1-3.0; P = .019), and overall survival (OS) (HR, 2.8; 95% CI, 1.4-5.7; P = .0045) compared with patients without detectable ctDNA. On multivariate analysis, MAFs ≥5% in exoDNA were a significant predictor of PFS (HR, 2.28; 95% CI, 1.18-4.40; P = .014) and OS (HR, 3.46; 95% CI, 1.40-8.50; P = .007). A multianalyte approach showed detection of both ctDNA and exoDNA MAFs ≥5% at baseline status to be a significant predictor of OS (HR, 7.73, 95% CI, 2.61-22.91, P = .00002) on multivariate analysis. In the longitudinal analysis, an MAF peak above 1% in exoDNA was significantly associated with radiologic progression (P = .0003). CONCLUSIONS In a prospective cohort of pancreatic cancer patients, we show how longitudinal monitoring using liquid biopsy samples through exoDNA and ctDNA provides both predictive and prognostic information relevant to therapeutic stratification.
The ZmbZIP22 Transcription Factor Regulates 27-kD γ-Zein Gene Transcription during Maize Endosperm Development[OPEN]

An unusual approach was used to identify a transcription factor that regulates γ-zein gene expression during maize endosperm development together with other transcription factors. Zeins are the most abundant storage proteins in maize (Zea mays) kernels, thereby affecting the nutritional quality and texture of this crop. 27-kD γ-zein is highly expressed and plays a crucial role in protein body formation. Several transcription factors (TFs) (O2, PBF1, OHP1, and OHP2) regulate the expression of the 27-kD γ-zein gene, but the complexity of its transcriptional regulation is not fully understood. Here, using probe affinity purification and mass spectrometry analysis, we identified ZmbZIP22, a TF that binds to the 27-kD γ-zein promoter. ZmbZIP22 is a bZIP-type TF that is specifically expressed in endosperm. ZmbZIP22 bound directly to the ACAGCTCA box in the 27-kD γ-zein promoter and activated its expression in wild tobacco (Nicotiana benthamiana) cells. 27-kD γ-zein gene expression was significantly reduced in CRISPR/Cas9-generated zmbzip22 mutants. ChIP-seq (chromatin immunoprecipitation coupled to high-throughput sequencing) confirmed that ZmbZIP22 binds to the 27-kD γ-zein promoter in vivo and identified additional direct targets of ZmbZIP22. ZmbZIP22 can interact with PBF1, OHP1, and OHP2, but not O2. Transactivation assays using various combinations of these TFs revealed multiple interaction modes for the transcriptional activity of the 27-kD γ-zein promoter. Therefore, ZmbZIP22 regulates 27-kD γ-zein gene expression together with other known TFs.
Differential expression of heat shock proteins and activation of mitogen‐activated protein kinases in A549 alveolar epithelial cells exposed to cigarette smoke extract

What is the central question of this study? What is the effect of cigarette smoke on cell death, oxidative damage, expression of heat shock proteins (HSPs) and activation of mitogen‐activated protein kinases (MAPKs) in A549 alveolar epithelial cells? What is the main finding and its importance? Cigarette smoke induces cytotoxicity and oxidative damage to A549 cells, increases expression of different HSPs and activates MAPK signalling pathways. This could be related to inflammatory response and apoptosis observed in lungs of patients with smoking‐related diseases.
Serum Stem Cell Growth Factor Beta for the Prediction of Therapy Response in Hepatocellular Carcinoma

Introduction Chronic inflammatory response is one of major contributors in the development of hepatocellular carcinoma (HCC). Inflammatory molecules, such as cytokines and growth factors in the circulation, can be useful in the diagnosis and prognosis of the patients. The stem cell growth factor beta (SCGFβ), a newly found protein, is a secreted sulfated glycoprotein and it functions as a growth factor for primitive hematopoietic progenitor cells. The level of SCGFβ had been reported to be elevated in several cancer types. However, there is very few or even no information on this protein in the study of HCC, even more in clinical studies. Methods A multiplex immunoassay panel of 48 cytokines and growth factors were utilized to screen 68 sera from 29 HCC patients at pretreatment (T0), 1 month (T1), and 6 months (T6) after treatment by either radiofrequency ablation (RF) or transarterial chemoembolization (TACE). Treatment response was evaluated according to mRECIST criteria. Results Immunoassay screening showed that the levels of IL-17, CTACK, TNFα, IL-2Rα, IL-8, and SCGFβ were different in Complete Responders (CR) and Nonresponders (NR) groups. At T0 and T1, the SCGFβ level was significantly the highest in NR (23.8 and 40.7 ng/mL, respectively), followed by early recurrence (25.4 and 25.0 ng/mL), and CR (6.7 and 5.3 ng/mL), independently from HCV, stages, and treatment type. Low basal SCGFβ level was associated with longer disease-free survival compared to high SCGFβ. Conclusion In this study, for the first time, we demonstrate that the high level of serum SCGFβ at pre- and posttreatment is associated with HCC nonresponsiveness.
Indication of Disrupted Temporal Structure in the Case of Thought Blocks in Schizophrenia: The Role of the Metastable Balance

This study is aimed at investigating probable disruption of the metastable balance relevant to a disruption of the mental processes observed in the neurophenomenal level. This disruption was found to occur under dense auditory verbal hallucinations (AVHs) which are accompanied by thought blocking (TB) phenomena. The entropy that quantifies the complexity of the spontaneous coupling has been used to describe the observed transitions. According to our findings, the high synchrony-derived entropy (SE) defines a metastable state, where formations of cortical areas are able to coordinate transiently under the demands of stimulus-oriented processes or other internal cognitive associations. It was also found that the disruption of the sensitive balance to the side of oversynergy (overconnectedness) rather than the side of independence (coincidental coupling) is relevant with functional fixations under the specific symptom of schizophrenia. An introduced measure relative to the persistence of coupling indicated that the overcoupled brain areas exhibit a kind of “stiffness” in processing incoherent phasic components. Our consideration enhances the understanding of the role the metastability plays in the interpretation of deeply subjective phenomena, such as AVHs and TBs that affect the normal information routing in the brain.
Association between MnSOD Val16Ala Polymorphism and Cancer Risk: Evidence from 33,098 Cases and 37,831 Controls

Manganese superoxide dismutase (MnSOD) plays a critical role in the defense against reactive oxygen species. The association between MnSOD Val16Ala polymorphism and cancer risk has been widely studied, but the results are contradictory. To obtain more precision on the association, we performed the current meta-analysis with 33,098 cases and 37,831 controls from 88 studies retrieved from PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of association. We found that the polymorphism was associated with an increased overall cancer risk (homozygous: OR = 1.09, 95% CI = 1.00–1.19; heterozygous: OR = 1.07, 95% CI = 1.02–1.12; dominant: OR = 1.08, 95% CI = 1.02–1.14; and allele comparison: OR = 1.06, 95% CI = 1.02–1.11). Stratification analysis further showed an increased risk for prostate cancer, Asians, Caucasians, population-based studies, hospital-based studies, low quality and high quality studies. However, the increased risk for MnSOD Val16Ala polymorphism among Asians needs further validation based on the false-positive report probability (FPRP) test. To summarize, this meta-analysis suggests that the MnSOD Val16Ala polymorphism is associated with significantly increased cancer risk, which needs further validation in single large studies.
Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats

Background and Aims Both paracetamol (PA) and phenacetin (PH) are analgesic and antipyretic agents. Part of phenacetin therapeutic activity is attributed to its metabolism into paracetamol. Paracetamol causes direct hepatic oxidative stress damage. The present study aimed to investigate the possible damaging effects of both PA and PH, when used in therapeutic doses, on rat liver and to compare the antioxidant and hepatoprotective effects of N-acetylcysteine (NAC), N-acetyl-methionine (NAM), and N-acetylglucosamine (NAG) against PA- or PH-induced hepatic damage. Methods 90 male Wistar albino rats (120-140 gm) were undertaken, categorized randomly into 9 groups of 10 rats each, and administered by gavage for 2 weeks with DMSO 1% (controls), PA, PA+NAC, PA+NAM, PA+NAG, PH, PH+NAC, PH+NAM, and PH+NAG. Biochemical assays of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), total thiols, and alpha-fetoprotein (AFP) in liver homogenates and serum assays of ALT, AST, 8-hydroxy guanine (8-OH-Gua), and AFP were done. Also histopathological examinations of liver tissues in various groups were done. Results PA and PH cause significant increase in hepatic levels of MDA, NO, and AFP and serum ALT, AST, and 8-OH-Gua levels, with significant decrease in hepatic GSH and total thiols. NAG and NAC significantly improve the PA- and PH-induced hepatic and blood, biochemical, and histopathological disturbances, respectively. Conclusions Both PA and PH induce oxidative stress in rat liver within their therapeutic doses. NAG and NAC in pharmacological doses can antagonize the oxidative damaging effect of both PA and PH.
Caveolin-1-Knockout Mouse as a Model of Inflammatory Diseases

Caveolin-1 (CAV1) is the scaffold protein of caveolae, which are minute invaginations of the cell membrane that are involved in endocytosis, cell signaling, and endothelial-mediated inflammation. CAV1 has also been reported to have a dual role as either a tumor suppressor or tumor promoter, depending on the type of cancer. Inflammation is an important player in tumor progression, but the role of caveolin-1 in generating an inflammatory milieu remains poorly characterized. We used a caveolin-1-knockout (CAV1−/−) mouse model to assess the inflammatory status via the quantification of the pro- and anti-inflammatory cytokine levels, as well as the ability of circulating lymphocytes to respond to nonspecific stimuli by producing cytokines. Here, we report that the CAV1−/− mice were characterized by a low-grade systemic proinflammatory status, with a moderate increase in the IL-6, TNF-α, and IL-12p70 levels. CAV1−/− circulating lymphocytes were more prone to cytokine production upon nonspecific stimulation than the wild-type lymphocytes. These results show that CAV1 involvement in cell homeostasis is more complex than previously revealed, as it plays a role in the inflammatory process. These findings indicate that the CAV1−/− mouse model could prove to be a useful tool for inflammation-related studies.
Prevalence of Stress and Associated Factors among Regular Students at Debre Birhan Governmental and Nongovernmental Health Science Colleges North Showa Zone, Amhara Region, Ethiopia 2016

Background Stress is very common among medical students across the globe with the prevalence of 80%. In Ethiopia, the prevalence is 47.7% among college students. Unless it is managed early, it leads to deterioration of academic performance and overall dissatisfaction with life and different serious health problems including anxiety, depression, and suicide. The objective of this study is to assess the prevalence of academic related stress among Debre Birhan governmental and nongovernmental health science college regular students 2015/16. Method A cross-sectional study was conducted on a sample of 422 health science students selected by stratified proportional random sampling at Debre Birhan governmental and nongovernmental health science colleges in North Shewa zone, Amhara region, Ethiopia in 2016. Data was collected using the Depression Anxiety Stress Scaling (DASS-21). The level of significance of association for multivariable was determined at P value <0.05. Result Prevalence of stress among Debre Birhan governmental and nongovernmental health science college regular students is 4.1%. There is a significant association between stress and sex AOR = 8.525 (1.023, 71.077), fear of examination AOR = 5.096 (1.183, 21.96), living in uncomfortable environment AOR = 14.86 (3.84, 57.515), and perceived present illness AOR = . 030 (0.003, 0.286). Depression and anxiety were also seen among 19.7% and 23.6%, respectively. Conclusion According to this study, the prevalence of stress among governmental and nongovernmental health science college regular students is not high. However, depression and anxiety were found to be higher than stress and they need immediate management plan. Colleges had better prepared simple screening tool and support students to prevent stress before they cause severe mental health problems.
Monthly or Weekly Supplementation with Cholecalciferol 20,000 IU in People Living with HIV: Results from a Nested Cohort Study

Background There is still considerable uncertainty in handling vitamin D deficiency in people living with HIV (PLWH), due to a lack of comparative data and the wide range of recommended daily intake. Nondaily supplementation might be preferred in many PLWH, but recommendation on dosing has not been established. We aimed to compare the efficacy of weekly versus monthly supplementation with cholecalciferol 20,000 IU in a group of PLWH with vitamin D deficiency in Western Europe. Study Design Longitudinal, retrospective nested cohort study of PLWH from two large clinical care centers in Munich, Germany. Results Of 307 patients with vitamin D deficiency, 124 patients received vitamin D supplementation (weekly supplementation in 84 (67.7%)). 46.4% and 22.5% of patients achieved 25(OH)D levels ≥30 ng/mL after 12 months of weekly and monthly supplementation with cholecalciferol 20,000 IU, respectively (p=0.011). Dosing interval as well as 25(OH)D baseline levels >15 ng/mL were associated with the normalization of 25(OH)D. Conclusion A higher rate of 25(OH)D level normalization can be achieved via weekly supplementation. For several PLWH, even a weekly dose of cholecalciferol 20,000 IU might not be adequate to maintain 25(OH)D levels >30 ng/mL without an initial “loading” dose. The response to supplementation is poorly predictable at an individual level.
SPIRITUALITY IN CONTEXT

The focus of this study is the Vincentian spirituality and its actualization among the Batak Sisters of Charity in North Sumatra, Indonesia. A significant issue in St Vincent de Paul''s life is that he discovered the destiny of his life, namely to be God''s Servant to the poor, following the foot step of Christ. How then Vincent did follow Chrits? In the time when the Catholic Church in France was in dire need of formation for those who wanted to become priests, Vincent took the initiative to provide an education for them. The Sisters in Schijndel, The Netherlands, chose Vincent''s way of being God''s Servant by running schools, when many parishes needed education. These Sisters went to North Sumatra. From them,the local girls received the new idea of being religious and move to dedicate themselves in parish ministry. This study shows that the actualization of Vincentian spirituality is shaped by the contexts in which the spirituality is lived out. Vincent followed Christ by i.e. giving education, while the Batak Sisters followed Jesus by caring for parishioners. Different contexts shaped these different ways of actualizing the same Vincentian spirituality.